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Parameswaran SA,Gopalakrishnan S
Non-Fermi Glasses: Localized Descendants of Fractionalized Metals.
Phys Rev Lett. 2017 Oct 06;119(14):146601
Non-Fermi liquids are metals that cannot be adiabatically deformed into free fermion states. We argue for the existence of "non-Fermi glasses," phases of interacting disordered fermions that are fully many-body localized (MBL), yet cannot be deformed into an Anderson insulator without an eigenstate phase transition. We explore the properties of such non-Fermi glasses, focusing on a specific solvable example. At high temperature, non-Fermi glasses have qualitatively similar spectral features to Anderson insulators. We identify a diagnostic based on ratios of correlators that sharply distinguishes between the two phases even at infinite temperature. Our results and diagnostic should generically apply to the high-temperature behavior of MBL descendants of fractionalized phases.
PMID: 29053309
Albright MBN,Martiny JBH
Dispersal alters bacterial diversity and composition in a natural community.
ISME J. 2017 Oct 20;
Dispersal is central to the evolution and maintenance of microbial diversity. Quantifying microbial dispersal and its role in shaping communities remains a challenge, however. Here, we manipulated a bacterial community's dispersal rate in a grassland ecosystem and test whether this altered diversity and composition. We constructed bags of two nylon mesh sizes that allowed more or less bacterial movement and filled them with an edible or inedible substrate, irradiated plant litter or nylon sheets. We measured changes in bacterial abundance (using flow cytometry) and composition (using 16S amplicon sequencing) in the bags weekly over 5 months. The dispersal treatment altered bacterial colonization rates and led to differences in the abundance, richness, evenness and composition of communities. Overall, the study demonstrates that dispersal influences the assembly of this natural bacterial community.The ISME Journal advance online publication, 20 October 2017; doi:10.1038/ismej.2017.161.
PMID: 29053150
Ma Y,Gao W,Shan H,Chen W,Shang W,Tao P,Song C,Addiego C,Deng T,Pan X,Wu J
Platinum-Based Nanowires as Active Catalysts toward Oxygen Reduction Reaction: In Situ Observation of Surface-Diffusion-Assisted, Solid-State Oriented Attachment.
Adv Mater. 2017 Oct 20;
Facile fabrication of advanced catalysts toward oxygen reduction reaction with improving activity and stability is significant for proton-exchange membrane fuel cells. Based on a generic solid-state reaction, this study reports a modified hydrogen-assisted, gas-phase synthesis for facile, scalable production of surfactant-free, thin, platinum-based nanowire-network electrocatalysts. The free-standing platinum and platinum-nickel alloy nanowires show improvements of up to 5.1 times and 10.9 times for mass activity with a minimum 2.6% loss after an accelerated durability test for 10k cycles; 8.5 times and 13.8 times for specific activity, respectively, compared to commercial Pt/C catalyst. In addition, combined with a wet impregnation method, different substrate-materials-supported platinum-based nanowires are obtained, which paves the way to practical application as a next-generation supported catalyst to replace Pt/C. The growth stages and formation mechanism are investigated by an in situ transmission electron microscopy study. It reveals that the free-standing platinum nanowires form in the solid state via metal-surface-diffusion-assisted oriented attachment of individual nanoparticles, and the interaction with gas molecules plays a critical role, which may represent a gas-molecular-adsorbate-modified growth in catalyst preparation.
PMID: 29052926
Lv C,Li F,Li X,Tian Y,Zhang Y,Sheng X,Song Y,Meng Q,Yuan S,Luan L,Andl T,Feng X,Jiao B,Xu M,Plikus MV,Dai X,Lengner C,Cui W,Ren F,Shuai J,Millar SE,Yu Z
MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists.
Nat Commun. 2017 Oct 19;8(1):1036
MicroRNA-mediated post-transcriptional regulation plays key roles in stem cell self-renewal and tumorigenesis. However, the in vivo functions of specific microRNAs in controlling mammary stem cell (MaSC) activity and breast cancer formation remain poorly understood. Here we show that miR-31 is highly expressed in MaSC-enriched mammary basal cell population and in mammary tumors, and is regulated by NF-?B signaling. We demonstrate that miR-31 promotes mammary epithelial proliferation and MaSC expansion at the expense of differentiation in vivo. Loss of miR-31 compromises mammary tumor growth, reduces the number of cancer stem cells, as well as decreases tumor-initiating ability and metastasis to the lung, supporting its pro-oncogenic function. MiR-31 modulates multiple signaling pathways, including Prlr/Stat5, TGFß and Wnt/ß-catenin. Particularly, it activates Wnt/ß-catenin signaling by directly targeting Wnt antagonists, including Dkk1. Importantly, Dkk1 overexpression partially rescues miR31-induced mammary defects. Together, these findings identify miR-31 as the key regulator of MaSC activity and breast tumorigenesis.
PMID: 29051494
Heilemann MV,Soderlund PD,Kehoe P,Brecht ML
A Transmedia Storytelling Intervention With Interactive Elements to Benefit Latinas' Mental Health: Feasibility, Acceptability, and Efficacy.
JMIR Ment Health. 2017 Oct 19;4(4):e47
Latinos report higher rates of depression and anxiety than US whites but are less likely to receive care. Transmedia storytelling interventions accessible on the Internet via smartphones, tablets, and computers hold promise for reducing reluctance to explore or get help for symptoms because they are private, convenient, and can reach large numbers of people, including Latinas with mental health needs.
PMID: 29051135
Sun Z,Yan L,Tang J,Qian Q,Lenberg J,Zhu D,Liu W,Wu K,Wang Y,Lu S
Brief Introduction of Current Technologies in Isolation of Broadly Neutralizing HIV-1 Antibodies.
Virus Res. 2017 Oct 16;
HIV/AIDS has become a worldwide pandemic. Before an effective HIV-1 vaccine eliciting broadly neutralizing monoclonal antibodies (bnmAbs) is fully developed, passive immunization for prevention and treatment of HIV-1 infection may alleviate the burden caused by the pandemic. Among HIV-1 infected individuals, about 20% of them generated cross-reactive neutralizing antibodies two to four years after infection, the details of which could provide knowledge for effective vaccine design. Recent progress in techniques for isolation of human broadly neutralizing antibodies has facilitated the study of passive immunization. The isolation and characterization of large panels of potent human broadly neutralizing antibodies has revealed new insights into the principles of antibody-mediated neutralization of HIV. In this paper, we review the current effective techniques in broadly neutralizing antibody isolation.
PMID: 29051051
Piltti KM,Cummings BJ,Carta K,Manughian-Peter A,Worne C,Singh K,Ong D,Maksymyuk Y,Khine M,Anderson AJ
Live-cell time-lapse imaging and single-cell tracking of in vitro cultured neural stem cells - Tools for analyzing dynamics of cell cycle, migration, and lineage selection.
Methods. 2017 Oct 16;
Neural stem cell (NSC) cultures have been considered technically challenging for time-lapse analysis due to high motility, photosensitivity, and growth at confluent densities. We have tested feasibility of long-term live-cell time-lapse analysis for NSC migration and differentiation studies. Here, we describe a method to study the dynamics of cell cycle, migration, and lineage selection in cultured multipotent mouse or human NSCs using single-cell tracking during a long-term, 7-14 day live-cell time-lapse analysis. We used in-house made PDMS inserts with five microwells on a glass coverslip petri-dish to constrain NSC into the area of acquisition during long-term live-cell imaging. In parallel, we have defined image acquisition settings for single-cell tracking of cell cycle dynamics using Fucci-reporter mouse NSC for 7 days as well as lineage selection and migration using human NSC for 14 days. Overall, we show that adjustments of live-cell analysis settings can extend the time period of single-cell tracking in mouse or human NSC from 24-72 hours up to 7-14 days and potentially longer. However, we emphasize that experimental use of repeated fluorescence imaging will require careful consideration of controls during acquisition and analysis.
PMID: 29050826
Kern MJ,Seto AH
Agreement and Differences Among Resting Coronary Physiological Indices: Are All Things Equal?
J Am Coll Cardiol. 2017 Oct 24;70(17):2124-2127
PMID: 29050559
Sibley MH,Rohde LA,Swanson JM,Hechtman LT,Molina BSG,Mitchell JT,Arnold LE,Caye A,Kennedy TM,Roy A,Stehli A,
Late-Onset ADHD Reconsidered With Comprehensive Repeated Assessments Between Ages 10 and 25.
Am J Psychiatry. 2017 Oct 20;:appiajp201717030298
Adolescents and young adults without childhood attention deficit hyperactivity disorder (ADHD) often present to clinics seeking stimulant medication for late-onset ADHD symptoms. Recent birth-cohort studies support the notion of late-onset ADHD, but these investigations are limited by relying on screening instruments to assess ADHD, not considering alternative causes of symptoms, or failing to obtain complete psychiatric histories. The authors address these limitations by examining psychiatric assessments administered longitudinally to the local normative comparison group of the Multimodal Treatment Study of ADHD.
PMID: 29050505
Neumann AR,Raedt R,Steenland HW,Sprengers M,Bzymek K,Navratilova Z,Mesina L,Xie J,Lapointe V,Kloosterman F,Vonck K,Boon PAJM,Soltesz I,McNaughton BL,Luczak A
Involvement of fast-spiking cells in ictal sequences during spontaneous seizures in rats with chronic temporal lobe epilepsy.
Brain. 2017 Sep 01;140(9):2355-2369
See Lenck-Santini (doi:10.1093/awx205) for a scientific commentary on this article.?Epileptic seizures represent altered neuronal network dynamics, but the temporal evolution and cellular substrates of the neuronal activity patterns associated with spontaneous seizures are not fully understood. We used simultaneous recordings from multiple neurons in the hippocampus and neocortex of rats with chronic temporal lobe epilepsy to demonstrate that subsets of cells discharge in a highly stereotypical sequential pattern during ictal events, and that these stereotypical patterns were reproducible across consecutive seizures. In contrast to the canonical view that principal cell discharges dominate ictal events, the ictal sequences were predominantly composed of fast-spiking, putative inhibitory neurons, which displayed unusually strong coupling to local field potential even before seizures. The temporal evolution of activity was characterized by unique dynamics where the most correlated neuronal pairs before seizure onset displayed the largest increases in correlation strength during the seizures. These results demonstrate the selective involvement of fast spiking interneurons in structured temporal sequences during spontaneous ictal events in hippocampal and neocortical circuits in experimental models of chronic temporal lobe epilepsy.
PMID: 29050390
Bonilha L,Hillis AE,Hickok G,den Ouden DB,Rorden C,Fridriksson J
Temporal lobe networks supporting the comprehension of spoken words.
Brain. 2017 Sep 01;140(9):2370-2380
Auditory word comprehension is a cognitive process that involves the transformation of auditory signals into abstract concepts. Traditional lesion-based studies of stroke survivors with aphasia have suggested that neocortical regions adjacent to auditory cortex are primarily responsible for word comprehension. However, recent primary progressive aphasia and normal neurophysiological studies have challenged this concept, suggesting that the left temporal pole is crucial for word comprehension. Due to its vasculature, the temporal pole is not commonly completely lesioned in stroke survivors and this heterogeneity may have prevented its identification in lesion-based studies of auditory comprehension. We aimed to resolve this controversy using a combined voxel-based-and structural connectome-lesion symptom mapping approach, since cortical dysfunction after stroke can arise from cortical damage or from white matter disconnection. Magnetic resonance imaging (T1-weighted and diffusion tensor imaging-based structural connectome), auditory word comprehension and object recognition tests were obtained from 67 chronic left hemisphere stroke survivors. We observed that damage to the inferior temporal gyrus, to the fusiform gyrus and to a white matter network including the left posterior temporal region and its connections to the middle temporal gyrus, inferior temporal gyrus, and cingulate cortex, was associated with word comprehension difficulties after factoring out object recognition. These results suggest that the posterior lateral and inferior temporal regions are crucial for word comprehension, serving as a hub to integrate auditory and conceptual processing. Early processing linking auditory words to concepts is situated in posterior lateral temporal regions, whereas additional and deeper levels of semantic processing likely require more anterior temporal regions.10.1093/brain/awx169_video1awx169media15555638084001.
PMID: 29050387
Marcano DC,Shin CS,Lee B,Isenhart LC,Liu X,Li F,Jester JV,Pflugfelder SC,Simpson J,Acharya G
Synergistic Cysteamine Delivery Nanowafer as an Efficacious Treatment Modality for Corneal Cystinosis.
Mol Pharm. 2016 Oct 03;13(10):3468-3477
A synergy between the polymer biomaterial and drug plays an important role in enhancing the therapeutic efficacy, improving the drug stability, and minimizing the local immune responses in the development of drug delivery systems. Particularly, in the case of ocular drug delivery, the need for the development of synergistic drug delivery system becomes more pronounced because of the wet ocular mucosal surface and highly innervated cornea, which elicit a strong inflammatory response to the instilled drug formulations. This article presents the development of a synergistic cysteamine delivery nanowafer to treat corneal cystinosis. Corneal cystinosis is a rare metabolic disease that causes the accumulation of cystine crystals in the cornea resulting in corneal opacity and loss of vision. It is treated with topical cysteamine (Cys) eye drops that need to be instilled 6-12 times a day throughout the patient's life, which causes side effects such as eye pain, redness, and ocular inflammation. As a result, compliance and treatment outcomes are severely compromised. To surmount these issues, we have developed a clinically translatable Cys nanowafer (Cys-NW) that can be simply applied on the eye with a fingertip. During the course of the drug release, Cys-NW slowly dissolves and fades away. The in vivo studies in cystinosin knockout mice demonstrated twice the therapeutic efficacy of Cys-NW containing 10 µg of Cys administered once a day, compared to 44 µg of Cys as topical eye drops administered twice a day. Furthermore, Cys-NW stabilizes Cys for up to four months at room temperature compared to topical Cys eye drops that need to be frozen or refrigerated and still remain active for only 1 week. The Cys-NW, because of its enhanced therapeutic efficacy, safety profile, and extended drug stability at room temperature, can be rapidly translated to the clinic for human trials.
PMID: 27571217
Lee BR,Joo KI,Choi ES,Jahng J,Kim H,Kim E
Evans blue dye-enhanced imaging of the brain microvessels using spectral focusing coherent anti-Stokes Raman scattering microscopy.
PLoS One. 2017;12(10):e0185519
We performed dye-enhanced imaging of mouse brain microvessels using spectral focusing coherent anti-Stokes Raman scattering (SF-CARS) microscopy. The resonant signals from C-H stretching in forward CARS usually show high background intensity in tissues, which makes CARS imaging of microvessels difficult. In this study, epi-detection of back-scattered SF-CARS signals showed a negligible background, but the overall intensity of resonant CARS signals was too low to observe the network of brain microvessels. Therefore, Evans blue (EB) dye was used as contrasting agent to enhance the back-scattered SF-CARS signals. Breakdown of brain microvessels by inducing hemorrhage in a mouse was clearly visualized using backward SF-CARS signals, following intravenous injection of EB. The improved visualization of brain microvessels with EB enhanced the sensitivity of SF-CARS, detecting not only the blood vessels themselves but their integrity as well in the brain vasculature.
PMID: 29049299
Mariano ER,Vetter TR,Kain ZN
The Perioperative Surgical Home Is Not Just a Name.
Anesth Analg. 2017 Nov;125(5):1443-1445
PMID: 29049108
Yeung EW,Craggs JG,Gizer IR
Comorbidity of Alcohol Use Disorder and Chronic Pain: Genetic Influences on Brain Reward and Stress Systems.
Alcohol Clin Exp Res. 2017 Oct 19;
Alcohol use disorder (AUD) is highly comorbid with chronic pain (CP). Evidence has suggested that neuroadaptive processes characterized by reward deficit and stress surfeit are involved in the development of AUD and pain chronification. Neurological data suggest that shared genetic architecture associated with the reward and stress systems may contribute to the comorbidity of AUD and CP. This monograph first delineates the prevailing theories of the development of AUD and pain chronification focusing on the reward and stress systems. It then provides a brief summary of relevant neurological findings followed by an evaluation of evidence documented by molecular genetic studies. Candidate gene association studies have provided some initial support for the genetic overlap between AUD and CP; however, these results must be interpreted with caution until studies with sufficient statistical power are conducted and replications obtained. Genomewide association studies have suggested a number of genes (e.g., TBX19, HTR7, and ADRA1A) that are either directly or indirectly related to the reward and stress systems in the AUD and CP literature. Evidence reviewed in this monograph suggests that shared genetic liability underlying the comorbidity between AUD and CP, if present, is likely to be complex. As the advancement in molecular genetic methods continues, future studies may show broader central nervous system involvement in AUD-CP comorbidity.
PMID: 29048744
Macchietto M,Angdembey D,Heidarpour N,Serra L,Rodriguez B,El-Ali N,Mortazavi A
Comparative Transcriptomics of Steinernema and Caenorhabditis Single Embryos Reveals Orthologous Gene Expression Convergence during Late Embryogenesis.
Genome Biol Evol. 2017 Oct 01;9(10):2681-2696
Cells express distinct sets of genes in a precise spatio-temporal manner during embryonic development. There is a wealth of information on the deterministic embryonic development of Caenorhabditis elegans, but much less is known about embryonic development in nematodes from other taxa, especially at the molecular level. We are interested in insect pathogenic nematodes from the genus Steinernema as models of parasitism and symbiosis as well as a satellite model for evolution in comparison to C. elegans. To explore gene expression differences across taxa, we sequenced the transcriptomes of single embryos of two Steinernema species and two Caenorhabditis species at 11 stages during embryonic development and found several interesting features. Our findings show that zygotic transcription initiates at different developmental stages in each species, with the Steinernema species initiating transcription earlier than Caenorhabditis. We found that ortholog expression conservation during development is higher at the later embryonic stages than at the earlier ones. The surprisingly higher conservation of orthologous gene expression in later embryonic stages strongly suggests a funnel-shaped model of embryonic developmental gene expression divergence in nematodes. This work provides novel insight into embryonic development across distantly related nematode species and demonstrates that the mechanisms controlling early development are more diverse than previously thought at the transcriptional level.
PMID: 29048526
Yafi F
Editorial comment on END-0390-OR.R2.
J Endourol. 2017 Oct 19;
No abstract.
PMID: 29048203
Amin A,Keshishian A,Vo L,Zhang Q,Dina O,Patel C,Odell K,Trocio J
Real-world comparison of all-cause hospitalizations, hospitalizations due to stroke and major bleeding, and costs for nonvalvular atrial fibrillation patients prescribed oral anticoagulants in a US health plan.
J Med Econ. 2017 Oct 19;:1-24
Compare the risk of all-cause hospitalization and hospitalizations due to stroke/systemic embolism (SE) and major bleeding as well as associated health care costs for nonvalvular atrial fibrillation (NVAF) patients initiating apixaban, dabigatran, rivaroxaban, or warfarin.
PMID: 29047304
Won SJ,Woo SH
Calcium Hydroxylapatite Pulmonary Embolism after Percutaneous Injection Laryngoplasty.
Yonsei Med J. 2017 Nov;58(6):1245-1248
Injection medialization laryngoplasty is a procedure that has many advantages in treating vocal fold paralysis; however, undesired complications can occur. We experienced a case of a pulmonary embolism, suspected in a patient who had undergone an injection laryngoplasty with calcium hydroxylapatite (CaHA). The patient suffered dyspnea after undergoing the injection laryngoplasty. Chest embolism computed tomography (CT) scan revealed a new lesion of enhancing materials at the pulmonary vasculature in the right upper lobe. The CaHA embolism was suspected, and the patient was treated with warfarin for 12 months. The patient's symptom of dyspnea nearly disappeared and a follow up chest embolism CT scan revealed no signs of the previous lesion. Thus, we would like to report this rare case along with a review of the literature.
PMID: 29047252
Abaza Y,Kantarjian HM,Faderl S,Jabbour E,Jain N,Thomas D,Kadia T,Borthakur G,Khoury JD,Burger J,Wierda W,O'Brien S,Konopleva M,Ferrajoli A,Kebriaei P,Dabaja B,Kornblau S,Alvarado Y,Daver N,Pemmaraju N,Bose P,Thompson P,Al Azzawi H,Kelly M,Garris R,Jain P,Garcia-Manero G,Cortes J,Ravandi F
Hyper-CVAD plus Nelarabine in Newly Diagnosed Adult T-Cell Acute Lymphoblastic Leukemia and T-Lymphoblastic Lymphoma.
Am J Hematol. 2017 Oct 19;
Nelarabine, a water soluble prodrug of 9-ß-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m(2) intravenously daily for 5 days. This was followed by thirty months of POMP maintenance chemotherapy with two additional cycles of nelarabine given instead of cycles 6 and 7 of POMP maintenance. Sixty-seven patients, including 40 with T-ALL and 26 with T-LBL, were enrolled. Complete response rates in both T-ALL and T-LBL were 87% and 100% respectively. Grade 3 to 4 neurotoxic adverse events were reported in 5 patients. There were 21 relapses (31%) including 2 after allogeneic stem cell transplantation. Median duration of follow-up was 42.5 months. The 3-year complete remission duration (CRD) and overall survival (OS) were 66% and 65%, respectively. Compared to our historic hyper-CVAD data, there was no survival benefit with the addition of nelarabine. In conclusion, hyper-CVAD plus nelarabine was well tolerated and active in the frontline treatment of adult T-ALL/LBL patients. This article is protected by copyright. All rights reserved.
PMID: 29047158
Kamel JG,Amber KT
Second primary cutaneous T-cell lymphoma in patients with non-Hodgkin lymphoma: a chicken-or-the-egg issue.
Int J Dermatol. 2017 Oct 19;
PMID: 29047113
Huynh LM,Huang E,Patel RM,Okhunov Z
Predictability and Practicality of Image-Based Scoring Systems for Patient Assessment and Outcome Stratification During Percutaneous Nephrolithotomy: a Contemporary Update.
Curr Urol Rep. 2017 Oct 18;18(12):95
Preoperative nomograms offer systematic and quantitative methods to assess patient- and stone-related characteristics and their impact on successful treatment and potential risk of complication. Discrepancies in the correlation of perioperative variables to patient outcomes have led to the individual development, validation, and application of four independent scoring systems for the percutaneous nephrolithotomy: Guy's stone score, S.T.O.N.E. nephrolithometry, Clinical Research Office of the Endourology Society nomogram, and Seoul National University Renal Stone Complexity. The optimal nomogram should have high predictive ability, be practically integrated into clinical use, and be widely applicable to urinary stone disease. Herein, we seek to provide a contemporary evaluation of the advantages, disadvantages, and commonalities of each scoring system. While the current data is insufficient to conclude which scoring system is destined to become the gold standard, it is crucial that a nephrolithometric scoring system be incorporated into common practice to improve surgical planning, patient counseling, and outcome assessment.
PMID: 29046986
Ravandi F,Othus M,O'Brien SM,Forman SJ,Ha CS,Wong JYC,Tallman MS,Paietta E,Racevskis J,Uy GL,Horowitz M,Takebe N,Little R,Borate U,Kebriaei P,Kingsbury L,Kantarjian HM,Radich JP,Erba HP,Appelbaum FR
US Intergroup Study of Chemotherapy Plus Dasatinib and Allogeneic Stem Cell Transplant in Philadelphia Chromosome Positive ALL.
Blood Adv. 2016 Dec 27;1(3):250-259
This multicenter trial was conducted to determine whether the addition of dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was feasible. Patients ≥ 18 and ≤ 60 years of age with newly diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate with dasatinib. Patients with an available matched sibling or unrelated donor underwent an allogeneic HCT in first complete remission (CR1) followed by daily dasatinib starting from day 100. Others received maintenance therapy with vincristine and prednisone for 2 years and dasatinib indefinitely. 97 patients (94 evaluable) with median age of 44 years (range, 20 - 60) and median WBC at presentation of 10 × 10(9)/L (range, 1 - 410 × 10(9)/L) were accrued. 83 (88%) patients achieved CR or CR with incomplete count recovery (CRi) and 41 underwent ASCT in CR1. Median follow-up is 36 months (range, 9 - 63). For the overall population, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) at 3 years were 69%, 55%, and 62%, respectively. The 12-month RFS and OS after transplant were 71% and 87%, respectively. Landmark analysis at 175 days from the time of CR/CRi (longest time to HCT), showed statistically superior advantages for RFS and OS (p=0.038 and 0.037, respectively) for the transplanted patients. Addition of dasatinib to chemotherapy and HCT for younger patients with Ph+ ALL is feasible and warrants further testing.
PMID: 29046900
Adams HD,Zeppel MJB,Anderegg WRL,Hartmann H,Landhäusser SM,Tissue DT,Huxman TE,Hudson PJ,Franz TE,Allen CD,Anderegg LDL,Barron-Gafford GA,Beerling DJ,Breshears DD,Brodribb TJ,Bugmann H,Cobb RC,Collins AD,Dickman LT,Duan H,Ewers BE,Galiano L,Galvez DA,Garcia-Forner N,Gaylord ML,Germino MJ,Gessler A,Hacke UG,Hakamada R,Hector A,Jenkins MW,Kane JM,Kolb TE,Law DJ,Lewis JD,Limousin JM,Love DM,Macalady AK,Martínez-Vilalta J,Mencuccini M,Mitchell PJ,Muss JD,O'Brien MJ,O'Grady AP,Pangle RE,Pinkard EA,Piper FI,Plaut JA,Pockman WT,Quirk J,Reinhardt K,Ripullone F,Ryan MG,Sala A,Sevanto S,Sperry JS,Vargas R,Vennetier M,Way DA,Xu C,Yepez EA,McDowell NG
A multi-species synthesis of physiological mechanisms in drought-induced tree mortality.
Nat Ecol Evol. 2017 Sep;1(9):1285-1291
Widespread tree mortality associated with drought has been observed on all forested continents and global change is expected to exacerbate vegetation vulnerability. Forest mortality has implications for future biosphere-atmosphere interactions of carbon, water and energy balance, and is poorly represented in dynamic vegetation models. Reducing uncertainty requires improved mortality projections founded on robust physiological processes. However, the proposed mechanisms of drought-induced mortality, including hydraulic failure and carbon starvation, are unresolved. A growing number of empirical studies have investigated these mechanisms, but data have not been consistently analysed across species and biomes using a standardized physiological framework. Here, we show that xylem hydraulic failure was ubiquitous across multiple tree taxa at drought-induced mortality. All species assessed had 60% or higher loss of xylem hydraulic conductivity, consistent with proposed theoretical and modelled survival thresholds. We found diverse responses in non-structural carbohydrate reserves at mortality, indicating that evidence supporting carbon starvation was not universal. Reduced non-structural carbohydrates were more common for gymnosperms than angiosperms, associated with xylem hydraulic vulnerability, and may have a role in reducing hydraulic function. Our finding that hydraulic failure at drought-induced mortality was persistent across species indicates that substantial improvement in vegetation modelling can be achieved using thresholds in hydraulic function.
PMID: 29046541
Turko AJ,Kültz D,Fudge D,Croll RP,Smith FM,Stoyek MR,Wright PA
Skeletal stiffening in an amphibious fish out of water is a response to increased body weight.
J Exp Biol. 2017 Oct 15;220(Pt 20):3621-3631
Terrestrial animals must support their bodies against gravity, while aquatic animals are effectively weightless because of buoyant support from water. Given this evolutionary history of minimal gravitational loading of fishes in water, it has been hypothesized that weight-responsive musculoskeletal systems evolved during the tetrapod invasion of land and are thus absent in fishes. Amphibious fishes, however, experience increased effective weight when out of water - are these fishes responsive to gravitational loading? Contrary to the tetrapod-origin hypothesis, we found that terrestrial acclimation reversibly increased gill arch stiffness (~60% increase) in the amphibious fish Kryptolebias marmoratus when loaded normally by gravity, but not under simulated microgravity. Quantitative proteomics analysis revealed that this change in mechanical properties occurred via increased abundance of proteins responsible for bone mineralization in other fishes as well as in tetrapods. Type X collagen, associated with endochondral bone growth, increased in abundance almost ninefold after terrestrial acclimation. Collagen isoforms known to promote extracellular matrix cross-linking and cause tissue stiffening, such as types IX and XII collagen, also increased in abundance. Finally, more densely packed collagen fibrils in both gill arches and filaments were observed microscopically in terrestrially acclimated fish. Our results demonstrate that the mechanical properties of the fish musculoskeletal system can be fine-tuned in response to changes in effective body weight using biochemical pathways similar to those in mammals, suggesting that weight sensing is an ancestral vertebrate trait rather than a tetrapod innovation.
PMID: 29046415
Non-Fermi Glasses: Localized Descendants of Fractionalized Metals.
Phys Rev Lett. 2017 Oct 06;119(14):146601
Non-Fermi liquids are metals that cannot be adiabatically deformed into free fermion states. We argue for the existence of "non-Fermi glasses," phases of interacting disordered fermions that are fully many-body localized (MBL), yet cannot be deformed into an Anderson insulator without an eigenstate phase transition. We explore the properties of such non-Fermi glasses, focusing on a specific solvable example. At high temperature, non-Fermi glasses have qualitatively similar spectral features to Anderson insulators. We identify a diagnostic based on ratios of correlators that sharply distinguishes between the two phases even at infinite temperature. Our results and diagnostic should generically apply to the high-temperature behavior of MBL descendants of fractionalized phases.
PMID: 29053309
Albright MBN,Martiny JBH
Dispersal alters bacterial diversity and composition in a natural community.
ISME J. 2017 Oct 20;
Dispersal is central to the evolution and maintenance of microbial diversity. Quantifying microbial dispersal and its role in shaping communities remains a challenge, however. Here, we manipulated a bacterial community's dispersal rate in a grassland ecosystem and test whether this altered diversity and composition. We constructed bags of two nylon mesh sizes that allowed more or less bacterial movement and filled them with an edible or inedible substrate, irradiated plant litter or nylon sheets. We measured changes in bacterial abundance (using flow cytometry) and composition (using 16S amplicon sequencing) in the bags weekly over 5 months. The dispersal treatment altered bacterial colonization rates and led to differences in the abundance, richness, evenness and composition of communities. Overall, the study demonstrates that dispersal influences the assembly of this natural bacterial community.The ISME Journal advance online publication, 20 October 2017; doi:10.1038/ismej.2017.161.
PMID: 29053150
Ma Y,Gao W,Shan H,Chen W,Shang W,Tao P,Song C,Addiego C,Deng T,Pan X,Wu J
Platinum-Based Nanowires as Active Catalysts toward Oxygen Reduction Reaction: In Situ Observation of Surface-Diffusion-Assisted, Solid-State Oriented Attachment.
Adv Mater. 2017 Oct 20;
Facile fabrication of advanced catalysts toward oxygen reduction reaction with improving activity and stability is significant for proton-exchange membrane fuel cells. Based on a generic solid-state reaction, this study reports a modified hydrogen-assisted, gas-phase synthesis for facile, scalable production of surfactant-free, thin, platinum-based nanowire-network electrocatalysts. The free-standing platinum and platinum-nickel alloy nanowires show improvements of up to 5.1 times and 10.9 times for mass activity with a minimum 2.6% loss after an accelerated durability test for 10k cycles; 8.5 times and 13.8 times for specific activity, respectively, compared to commercial Pt/C catalyst. In addition, combined with a wet impregnation method, different substrate-materials-supported platinum-based nanowires are obtained, which paves the way to practical application as a next-generation supported catalyst to replace Pt/C. The growth stages and formation mechanism are investigated by an in situ transmission electron microscopy study. It reveals that the free-standing platinum nanowires form in the solid state via metal-surface-diffusion-assisted oriented attachment of individual nanoparticles, and the interaction with gas molecules plays a critical role, which may represent a gas-molecular-adsorbate-modified growth in catalyst preparation.
PMID: 29052926
Lv C,Li F,Li X,Tian Y,Zhang Y,Sheng X,Song Y,Meng Q,Yuan S,Luan L,Andl T,Feng X,Jiao B,Xu M,Plikus MV,Dai X,Lengner C,Cui W,Ren F,Shuai J,Millar SE,Yu Z
MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists.
Nat Commun. 2017 Oct 19;8(1):1036
MicroRNA-mediated post-transcriptional regulation plays key roles in stem cell self-renewal and tumorigenesis. However, the in vivo functions of specific microRNAs in controlling mammary stem cell (MaSC) activity and breast cancer formation remain poorly understood. Here we show that miR-31 is highly expressed in MaSC-enriched mammary basal cell population and in mammary tumors, and is regulated by NF-?B signaling. We demonstrate that miR-31 promotes mammary epithelial proliferation and MaSC expansion at the expense of differentiation in vivo. Loss of miR-31 compromises mammary tumor growth, reduces the number of cancer stem cells, as well as decreases tumor-initiating ability and metastasis to the lung, supporting its pro-oncogenic function. MiR-31 modulates multiple signaling pathways, including Prlr/Stat5, TGFß and Wnt/ß-catenin. Particularly, it activates Wnt/ß-catenin signaling by directly targeting Wnt antagonists, including Dkk1. Importantly, Dkk1 overexpression partially rescues miR31-induced mammary defects. Together, these findings identify miR-31 as the key regulator of MaSC activity and breast tumorigenesis.
PMID: 29051494
Heilemann MV,Soderlund PD,Kehoe P,Brecht ML
A Transmedia Storytelling Intervention With Interactive Elements to Benefit Latinas' Mental Health: Feasibility, Acceptability, and Efficacy.
JMIR Ment Health. 2017 Oct 19;4(4):e47
Latinos report higher rates of depression and anxiety than US whites but are less likely to receive care. Transmedia storytelling interventions accessible on the Internet via smartphones, tablets, and computers hold promise for reducing reluctance to explore or get help for symptoms because they are private, convenient, and can reach large numbers of people, including Latinas with mental health needs.
PMID: 29051135
Sun Z,Yan L,Tang J,Qian Q,Lenberg J,Zhu D,Liu W,Wu K,Wang Y,Lu S
Brief Introduction of Current Technologies in Isolation of Broadly Neutralizing HIV-1 Antibodies.
Virus Res. 2017 Oct 16;
HIV/AIDS has become a worldwide pandemic. Before an effective HIV-1 vaccine eliciting broadly neutralizing monoclonal antibodies (bnmAbs) is fully developed, passive immunization for prevention and treatment of HIV-1 infection may alleviate the burden caused by the pandemic. Among HIV-1 infected individuals, about 20% of them generated cross-reactive neutralizing antibodies two to four years after infection, the details of which could provide knowledge for effective vaccine design. Recent progress in techniques for isolation of human broadly neutralizing antibodies has facilitated the study of passive immunization. The isolation and characterization of large panels of potent human broadly neutralizing antibodies has revealed new insights into the principles of antibody-mediated neutralization of HIV. In this paper, we review the current effective techniques in broadly neutralizing antibody isolation.
PMID: 29051051
Piltti KM,Cummings BJ,Carta K,Manughian-Peter A,Worne C,Singh K,Ong D,Maksymyuk Y,Khine M,Anderson AJ
Live-cell time-lapse imaging and single-cell tracking of in vitro cultured neural stem cells - Tools for analyzing dynamics of cell cycle, migration, and lineage selection.
Methods. 2017 Oct 16;
Neural stem cell (NSC) cultures have been considered technically challenging for time-lapse analysis due to high motility, photosensitivity, and growth at confluent densities. We have tested feasibility of long-term live-cell time-lapse analysis for NSC migration and differentiation studies. Here, we describe a method to study the dynamics of cell cycle, migration, and lineage selection in cultured multipotent mouse or human NSCs using single-cell tracking during a long-term, 7-14 day live-cell time-lapse analysis. We used in-house made PDMS inserts with five microwells on a glass coverslip petri-dish to constrain NSC into the area of acquisition during long-term live-cell imaging. In parallel, we have defined image acquisition settings for single-cell tracking of cell cycle dynamics using Fucci-reporter mouse NSC for 7 days as well as lineage selection and migration using human NSC for 14 days. Overall, we show that adjustments of live-cell analysis settings can extend the time period of single-cell tracking in mouse or human NSC from 24-72 hours up to 7-14 days and potentially longer. However, we emphasize that experimental use of repeated fluorescence imaging will require careful consideration of controls during acquisition and analysis.
PMID: 29050826
Kern MJ,Seto AH
Agreement and Differences Among Resting Coronary Physiological Indices: Are All Things Equal?
J Am Coll Cardiol. 2017 Oct 24;70(17):2124-2127
PMID: 29050559
Sibley MH,Rohde LA,Swanson JM,Hechtman LT,Molina BSG,Mitchell JT,Arnold LE,Caye A,Kennedy TM,Roy A,Stehli A,
Late-Onset ADHD Reconsidered With Comprehensive Repeated Assessments Between Ages 10 and 25.
Am J Psychiatry. 2017 Oct 20;:appiajp201717030298
Adolescents and young adults without childhood attention deficit hyperactivity disorder (ADHD) often present to clinics seeking stimulant medication for late-onset ADHD symptoms. Recent birth-cohort studies support the notion of late-onset ADHD, but these investigations are limited by relying on screening instruments to assess ADHD, not considering alternative causes of symptoms, or failing to obtain complete psychiatric histories. The authors address these limitations by examining psychiatric assessments administered longitudinally to the local normative comparison group of the Multimodal Treatment Study of ADHD.
PMID: 29050505
Neumann AR,Raedt R,Steenland HW,Sprengers M,Bzymek K,Navratilova Z,Mesina L,Xie J,Lapointe V,Kloosterman F,Vonck K,Boon PAJM,Soltesz I,McNaughton BL,Luczak A
Involvement of fast-spiking cells in ictal sequences during spontaneous seizures in rats with chronic temporal lobe epilepsy.
Brain. 2017 Sep 01;140(9):2355-2369
See Lenck-Santini (doi:10.1093/awx205) for a scientific commentary on this article.?Epileptic seizures represent altered neuronal network dynamics, but the temporal evolution and cellular substrates of the neuronal activity patterns associated with spontaneous seizures are not fully understood. We used simultaneous recordings from multiple neurons in the hippocampus and neocortex of rats with chronic temporal lobe epilepsy to demonstrate that subsets of cells discharge in a highly stereotypical sequential pattern during ictal events, and that these stereotypical patterns were reproducible across consecutive seizures. In contrast to the canonical view that principal cell discharges dominate ictal events, the ictal sequences were predominantly composed of fast-spiking, putative inhibitory neurons, which displayed unusually strong coupling to local field potential even before seizures. The temporal evolution of activity was characterized by unique dynamics where the most correlated neuronal pairs before seizure onset displayed the largest increases in correlation strength during the seizures. These results demonstrate the selective involvement of fast spiking interneurons in structured temporal sequences during spontaneous ictal events in hippocampal and neocortical circuits in experimental models of chronic temporal lobe epilepsy.
PMID: 29050390
Bonilha L,Hillis AE,Hickok G,den Ouden DB,Rorden C,Fridriksson J
Temporal lobe networks supporting the comprehension of spoken words.
Brain. 2017 Sep 01;140(9):2370-2380
Auditory word comprehension is a cognitive process that involves the transformation of auditory signals into abstract concepts. Traditional lesion-based studies of stroke survivors with aphasia have suggested that neocortical regions adjacent to auditory cortex are primarily responsible for word comprehension. However, recent primary progressive aphasia and normal neurophysiological studies have challenged this concept, suggesting that the left temporal pole is crucial for word comprehension. Due to its vasculature, the temporal pole is not commonly completely lesioned in stroke survivors and this heterogeneity may have prevented its identification in lesion-based studies of auditory comprehension. We aimed to resolve this controversy using a combined voxel-based-and structural connectome-lesion symptom mapping approach, since cortical dysfunction after stroke can arise from cortical damage or from white matter disconnection. Magnetic resonance imaging (T1-weighted and diffusion tensor imaging-based structural connectome), auditory word comprehension and object recognition tests were obtained from 67 chronic left hemisphere stroke survivors. We observed that damage to the inferior temporal gyrus, to the fusiform gyrus and to a white matter network including the left posterior temporal region and its connections to the middle temporal gyrus, inferior temporal gyrus, and cingulate cortex, was associated with word comprehension difficulties after factoring out object recognition. These results suggest that the posterior lateral and inferior temporal regions are crucial for word comprehension, serving as a hub to integrate auditory and conceptual processing. Early processing linking auditory words to concepts is situated in posterior lateral temporal regions, whereas additional and deeper levels of semantic processing likely require more anterior temporal regions.10.1093/brain/awx169_video1awx169media15555638084001.
PMID: 29050387
Marcano DC,Shin CS,Lee B,Isenhart LC,Liu X,Li F,Jester JV,Pflugfelder SC,Simpson J,Acharya G
Synergistic Cysteamine Delivery Nanowafer as an Efficacious Treatment Modality for Corneal Cystinosis.
Mol Pharm. 2016 Oct 03;13(10):3468-3477
A synergy between the polymer biomaterial and drug plays an important role in enhancing the therapeutic efficacy, improving the drug stability, and minimizing the local immune responses in the development of drug delivery systems. Particularly, in the case of ocular drug delivery, the need for the development of synergistic drug delivery system becomes more pronounced because of the wet ocular mucosal surface and highly innervated cornea, which elicit a strong inflammatory response to the instilled drug formulations. This article presents the development of a synergistic cysteamine delivery nanowafer to treat corneal cystinosis. Corneal cystinosis is a rare metabolic disease that causes the accumulation of cystine crystals in the cornea resulting in corneal opacity and loss of vision. It is treated with topical cysteamine (Cys) eye drops that need to be instilled 6-12 times a day throughout the patient's life, which causes side effects such as eye pain, redness, and ocular inflammation. As a result, compliance and treatment outcomes are severely compromised. To surmount these issues, we have developed a clinically translatable Cys nanowafer (Cys-NW) that can be simply applied on the eye with a fingertip. During the course of the drug release, Cys-NW slowly dissolves and fades away. The in vivo studies in cystinosin knockout mice demonstrated twice the therapeutic efficacy of Cys-NW containing 10 µg of Cys administered once a day, compared to 44 µg of Cys as topical eye drops administered twice a day. Furthermore, Cys-NW stabilizes Cys for up to four months at room temperature compared to topical Cys eye drops that need to be frozen or refrigerated and still remain active for only 1 week. The Cys-NW, because of its enhanced therapeutic efficacy, safety profile, and extended drug stability at room temperature, can be rapidly translated to the clinic for human trials.
PMID: 27571217
Lee BR,Joo KI,Choi ES,Jahng J,Kim H,Kim E
Evans blue dye-enhanced imaging of the brain microvessels using spectral focusing coherent anti-Stokes Raman scattering microscopy.
PLoS One. 2017;12(10):e0185519
We performed dye-enhanced imaging of mouse brain microvessels using spectral focusing coherent anti-Stokes Raman scattering (SF-CARS) microscopy. The resonant signals from C-H stretching in forward CARS usually show high background intensity in tissues, which makes CARS imaging of microvessels difficult. In this study, epi-detection of back-scattered SF-CARS signals showed a negligible background, but the overall intensity of resonant CARS signals was too low to observe the network of brain microvessels. Therefore, Evans blue (EB) dye was used as contrasting agent to enhance the back-scattered SF-CARS signals. Breakdown of brain microvessels by inducing hemorrhage in a mouse was clearly visualized using backward SF-CARS signals, following intravenous injection of EB. The improved visualization of brain microvessels with EB enhanced the sensitivity of SF-CARS, detecting not only the blood vessels themselves but their integrity as well in the brain vasculature.
PMID: 29049299
Mariano ER,Vetter TR,Kain ZN
The Perioperative Surgical Home Is Not Just a Name.
Anesth Analg. 2017 Nov;125(5):1443-1445
PMID: 29049108
Yeung EW,Craggs JG,Gizer IR
Comorbidity of Alcohol Use Disorder and Chronic Pain: Genetic Influences on Brain Reward and Stress Systems.
Alcohol Clin Exp Res. 2017 Oct 19;
Alcohol use disorder (AUD) is highly comorbid with chronic pain (CP). Evidence has suggested that neuroadaptive processes characterized by reward deficit and stress surfeit are involved in the development of AUD and pain chronification. Neurological data suggest that shared genetic architecture associated with the reward and stress systems may contribute to the comorbidity of AUD and CP. This monograph first delineates the prevailing theories of the development of AUD and pain chronification focusing on the reward and stress systems. It then provides a brief summary of relevant neurological findings followed by an evaluation of evidence documented by molecular genetic studies. Candidate gene association studies have provided some initial support for the genetic overlap between AUD and CP; however, these results must be interpreted with caution until studies with sufficient statistical power are conducted and replications obtained. Genomewide association studies have suggested a number of genes (e.g., TBX19, HTR7, and ADRA1A) that are either directly or indirectly related to the reward and stress systems in the AUD and CP literature. Evidence reviewed in this monograph suggests that shared genetic liability underlying the comorbidity between AUD and CP, if present, is likely to be complex. As the advancement in molecular genetic methods continues, future studies may show broader central nervous system involvement in AUD-CP comorbidity.
PMID: 29048744
Macchietto M,Angdembey D,Heidarpour N,Serra L,Rodriguez B,El-Ali N,Mortazavi A
Comparative Transcriptomics of Steinernema and Caenorhabditis Single Embryos Reveals Orthologous Gene Expression Convergence during Late Embryogenesis.
Genome Biol Evol. 2017 Oct 01;9(10):2681-2696
Cells express distinct sets of genes in a precise spatio-temporal manner during embryonic development. There is a wealth of information on the deterministic embryonic development of Caenorhabditis elegans, but much less is known about embryonic development in nematodes from other taxa, especially at the molecular level. We are interested in insect pathogenic nematodes from the genus Steinernema as models of parasitism and symbiosis as well as a satellite model for evolution in comparison to C. elegans. To explore gene expression differences across taxa, we sequenced the transcriptomes of single embryos of two Steinernema species and two Caenorhabditis species at 11 stages during embryonic development and found several interesting features. Our findings show that zygotic transcription initiates at different developmental stages in each species, with the Steinernema species initiating transcription earlier than Caenorhabditis. We found that ortholog expression conservation during development is higher at the later embryonic stages than at the earlier ones. The surprisingly higher conservation of orthologous gene expression in later embryonic stages strongly suggests a funnel-shaped model of embryonic developmental gene expression divergence in nematodes. This work provides novel insight into embryonic development across distantly related nematode species and demonstrates that the mechanisms controlling early development are more diverse than previously thought at the transcriptional level.
PMID: 29048526
Yafi F
Editorial comment on END-0390-OR.R2.
J Endourol. 2017 Oct 19;
No abstract.
PMID: 29048203
Amin A,Keshishian A,Vo L,Zhang Q,Dina O,Patel C,Odell K,Trocio J
Real-world comparison of all-cause hospitalizations, hospitalizations due to stroke and major bleeding, and costs for nonvalvular atrial fibrillation patients prescribed oral anticoagulants in a US health plan.
J Med Econ. 2017 Oct 19;:1-24
Compare the risk of all-cause hospitalization and hospitalizations due to stroke/systemic embolism (SE) and major bleeding as well as associated health care costs for nonvalvular atrial fibrillation (NVAF) patients initiating apixaban, dabigatran, rivaroxaban, or warfarin.
PMID: 29047304
Won SJ,Woo SH
Calcium Hydroxylapatite Pulmonary Embolism after Percutaneous Injection Laryngoplasty.
Yonsei Med J. 2017 Nov;58(6):1245-1248
Injection medialization laryngoplasty is a procedure that has many advantages in treating vocal fold paralysis; however, undesired complications can occur. We experienced a case of a pulmonary embolism, suspected in a patient who had undergone an injection laryngoplasty with calcium hydroxylapatite (CaHA). The patient suffered dyspnea after undergoing the injection laryngoplasty. Chest embolism computed tomography (CT) scan revealed a new lesion of enhancing materials at the pulmonary vasculature in the right upper lobe. The CaHA embolism was suspected, and the patient was treated with warfarin for 12 months. The patient's symptom of dyspnea nearly disappeared and a follow up chest embolism CT scan revealed no signs of the previous lesion. Thus, we would like to report this rare case along with a review of the literature.
PMID: 29047252
Abaza Y,Kantarjian HM,Faderl S,Jabbour E,Jain N,Thomas D,Kadia T,Borthakur G,Khoury JD,Burger J,Wierda W,O'Brien S,Konopleva M,Ferrajoli A,Kebriaei P,Dabaja B,Kornblau S,Alvarado Y,Daver N,Pemmaraju N,Bose P,Thompson P,Al Azzawi H,Kelly M,Garris R,Jain P,Garcia-Manero G,Cortes J,Ravandi F
Hyper-CVAD plus Nelarabine in Newly Diagnosed Adult T-Cell Acute Lymphoblastic Leukemia and T-Lymphoblastic Lymphoma.
Am J Hematol. 2017 Oct 19;
Nelarabine, a water soluble prodrug of 9-ß-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m(2) intravenously daily for 5 days. This was followed by thirty months of POMP maintenance chemotherapy with two additional cycles of nelarabine given instead of cycles 6 and 7 of POMP maintenance. Sixty-seven patients, including 40 with T-ALL and 26 with T-LBL, were enrolled. Complete response rates in both T-ALL and T-LBL were 87% and 100% respectively. Grade 3 to 4 neurotoxic adverse events were reported in 5 patients. There were 21 relapses (31%) including 2 after allogeneic stem cell transplantation. Median duration of follow-up was 42.5 months. The 3-year complete remission duration (CRD) and overall survival (OS) were 66% and 65%, respectively. Compared to our historic hyper-CVAD data, there was no survival benefit with the addition of nelarabine. In conclusion, hyper-CVAD plus nelarabine was well tolerated and active in the frontline treatment of adult T-ALL/LBL patients. This article is protected by copyright. All rights reserved.
PMID: 29047158
Kamel JG,Amber KT
Second primary cutaneous T-cell lymphoma in patients with non-Hodgkin lymphoma: a chicken-or-the-egg issue.
Int J Dermatol. 2017 Oct 19;
PMID: 29047113
Huynh LM,Huang E,Patel RM,Okhunov Z
Predictability and Practicality of Image-Based Scoring Systems for Patient Assessment and Outcome Stratification During Percutaneous Nephrolithotomy: a Contemporary Update.
Curr Urol Rep. 2017 Oct 18;18(12):95
Preoperative nomograms offer systematic and quantitative methods to assess patient- and stone-related characteristics and their impact on successful treatment and potential risk of complication. Discrepancies in the correlation of perioperative variables to patient outcomes have led to the individual development, validation, and application of four independent scoring systems for the percutaneous nephrolithotomy: Guy's stone score, S.T.O.N.E. nephrolithometry, Clinical Research Office of the Endourology Society nomogram, and Seoul National University Renal Stone Complexity. The optimal nomogram should have high predictive ability, be practically integrated into clinical use, and be widely applicable to urinary stone disease. Herein, we seek to provide a contemporary evaluation of the advantages, disadvantages, and commonalities of each scoring system. While the current data is insufficient to conclude which scoring system is destined to become the gold standard, it is crucial that a nephrolithometric scoring system be incorporated into common practice to improve surgical planning, patient counseling, and outcome assessment.
PMID: 29046986
Ravandi F,Othus M,O'Brien SM,Forman SJ,Ha CS,Wong JYC,Tallman MS,Paietta E,Racevskis J,Uy GL,Horowitz M,Takebe N,Little R,Borate U,Kebriaei P,Kingsbury L,Kantarjian HM,Radich JP,Erba HP,Appelbaum FR
US Intergroup Study of Chemotherapy Plus Dasatinib and Allogeneic Stem Cell Transplant in Philadelphia Chromosome Positive ALL.
Blood Adv. 2016 Dec 27;1(3):250-259
This multicenter trial was conducted to determine whether the addition of dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was feasible. Patients ≥ 18 and ≤ 60 years of age with newly diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate with dasatinib. Patients with an available matched sibling or unrelated donor underwent an allogeneic HCT in first complete remission (CR1) followed by daily dasatinib starting from day 100. Others received maintenance therapy with vincristine and prednisone for 2 years and dasatinib indefinitely. 97 patients (94 evaluable) with median age of 44 years (range, 20 - 60) and median WBC at presentation of 10 × 10(9)/L (range, 1 - 410 × 10(9)/L) were accrued. 83 (88%) patients achieved CR or CR with incomplete count recovery (CRi) and 41 underwent ASCT in CR1. Median follow-up is 36 months (range, 9 - 63). For the overall population, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) at 3 years were 69%, 55%, and 62%, respectively. The 12-month RFS and OS after transplant were 71% and 87%, respectively. Landmark analysis at 175 days from the time of CR/CRi (longest time to HCT), showed statistically superior advantages for RFS and OS (p=0.038 and 0.037, respectively) for the transplanted patients. Addition of dasatinib to chemotherapy and HCT for younger patients with Ph+ ALL is feasible and warrants further testing.
PMID: 29046900
Adams HD,Zeppel MJB,Anderegg WRL,Hartmann H,Landhäusser SM,Tissue DT,Huxman TE,Hudson PJ,Franz TE,Allen CD,Anderegg LDL,Barron-Gafford GA,Beerling DJ,Breshears DD,Brodribb TJ,Bugmann H,Cobb RC,Collins AD,Dickman LT,Duan H,Ewers BE,Galiano L,Galvez DA,Garcia-Forner N,Gaylord ML,Germino MJ,Gessler A,Hacke UG,Hakamada R,Hector A,Jenkins MW,Kane JM,Kolb TE,Law DJ,Lewis JD,Limousin JM,Love DM,Macalady AK,Martínez-Vilalta J,Mencuccini M,Mitchell PJ,Muss JD,O'Brien MJ,O'Grady AP,Pangle RE,Pinkard EA,Piper FI,Plaut JA,Pockman WT,Quirk J,Reinhardt K,Ripullone F,Ryan MG,Sala A,Sevanto S,Sperry JS,Vargas R,Vennetier M,Way DA,Xu C,Yepez EA,McDowell NG
A multi-species synthesis of physiological mechanisms in drought-induced tree mortality.
Nat Ecol Evol. 2017 Sep;1(9):1285-1291
Widespread tree mortality associated with drought has been observed on all forested continents and global change is expected to exacerbate vegetation vulnerability. Forest mortality has implications for future biosphere-atmosphere interactions of carbon, water and energy balance, and is poorly represented in dynamic vegetation models. Reducing uncertainty requires improved mortality projections founded on robust physiological processes. However, the proposed mechanisms of drought-induced mortality, including hydraulic failure and carbon starvation, are unresolved. A growing number of empirical studies have investigated these mechanisms, but data have not been consistently analysed across species and biomes using a standardized physiological framework. Here, we show that xylem hydraulic failure was ubiquitous across multiple tree taxa at drought-induced mortality. All species assessed had 60% or higher loss of xylem hydraulic conductivity, consistent with proposed theoretical and modelled survival thresholds. We found diverse responses in non-structural carbohydrate reserves at mortality, indicating that evidence supporting carbon starvation was not universal. Reduced non-structural carbohydrates were more common for gymnosperms than angiosperms, associated with xylem hydraulic vulnerability, and may have a role in reducing hydraulic function. Our finding that hydraulic failure at drought-induced mortality was persistent across species indicates that substantial improvement in vegetation modelling can be achieved using thresholds in hydraulic function.
PMID: 29046541
Turko AJ,Kültz D,Fudge D,Croll RP,Smith FM,Stoyek MR,Wright PA
Skeletal stiffening in an amphibious fish out of water is a response to increased body weight.
J Exp Biol. 2017 Oct 15;220(Pt 20):3621-3631
Terrestrial animals must support their bodies against gravity, while aquatic animals are effectively weightless because of buoyant support from water. Given this evolutionary history of minimal gravitational loading of fishes in water, it has been hypothesized that weight-responsive musculoskeletal systems evolved during the tetrapod invasion of land and are thus absent in fishes. Amphibious fishes, however, experience increased effective weight when out of water - are these fishes responsive to gravitational loading? Contrary to the tetrapod-origin hypothesis, we found that terrestrial acclimation reversibly increased gill arch stiffness (~60% increase) in the amphibious fish Kryptolebias marmoratus when loaded normally by gravity, but not under simulated microgravity. Quantitative proteomics analysis revealed that this change in mechanical properties occurred via increased abundance of proteins responsible for bone mineralization in other fishes as well as in tetrapods. Type X collagen, associated with endochondral bone growth, increased in abundance almost ninefold after terrestrial acclimation. Collagen isoforms known to promote extracellular matrix cross-linking and cause tissue stiffening, such as types IX and XII collagen, also increased in abundance. Finally, more densely packed collagen fibrils in both gill arches and filaments were observed microscopically in terrestrially acclimated fish. Our results demonstrate that the mechanical properties of the fish musculoskeletal system can be fine-tuned in response to changes in effective body weight using biochemical pathways similar to those in mammals, suggesting that weight sensing is an ancestral vertebrate trait rather than a tetrapod innovation.
PMID: 29046415
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