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Cao H,Xiao Z,Zhang Y,Kwong T,Danish SF,Weiner J,Wang X,Yue N,Dai Z,Kuang Y,Bai Y,Nie K
Dosimetric comparisons of different hypofractionated stereotactic radiotherapy techniques in treating intracranial tumors > 3 cm in longest diameter.
J Neurosurg. 2019 Mar 22;:1-9
OBJECTIVEThe authors sought to compare the dosimetric quality of hypofractionated stereotactic radiosurgery in treating sizeable brain tumors across the following treatment platforms: GammaKnife (GK) Icon, CyberKnife (CK) G4, volumetric modulated arc therapy (VMAT) on the Varian TrueBeam STx, double scattering proton therapy (DSPT) on the Mevion S250, and intensity modulated proton therapy (IMPT) on the Varian ProBeam.METHODSIn this retrospective study, stereotactic radiotherapy treatment plans were generated for 10 patients with sizeable brain tumors (> 3 cm in longest diameter) who had been treated with VMAT. Six treatment plans, 20-30 Gy in 5 fractions, were generated for each patient using the same constraints for each of the following radiosurgical methods: 1) GK, 2) CK, 3) coplanar arc VMAT (VMAT-C), 4) noncoplanar arc VMAT (VMAT-NC), 5) DSPT, and 6) IMPT. The coverage; conformity index; gradient index (GI); homogeneity index; mean and maximum point dose of organs at risk; total dose volume (V) in Gy to the normal brain for 2 Gy (V2), 5 Gy (V5), and 12 Gy (V12); and integral dose were compared across all platforms.RESULTSAmong the 6 techniques, GK consistently produced a sharper dose falloff despite a greater central target dose. GK gave the lowest GI, with a mean of 2.7 ± 0.1, followed by CK (2.9 ± 0.1), VMAT-NC (3.1 ± 0.3), and VMAT-C (3.5 ± 0.3). The highest mean GIs for the proton beam treatments were 3.8 ± 0.4 for DSPT and 3.9 ± 0.4 for IMPT. The GK consistently targeted the lowest normal brain volume, delivering 5 to 12 Gy when treating relatively smaller- to intermediate-sized lesions (less than 15-20 cm3). Yet, the differences across the 6 modalities relative to GK decreased with the increase of target volume. In particular, the proton treatments delivered the lowest V5 to the normal brain when the target size was over 15-20 cm3 and also produced the lowest integral dose to the normal brain regardless of the target size.CONCLUSIONSThis study provides an insightful understanding of dosimetric quality from both photon and proton treatment across the most advanced stereotactic radiotherapy platforms.
PMID: 30901747

Solanki S,McPartlan P,Xu D,Sato BK
Success with EASE: Who benefits from a STEM learning community?
PLoS One. 2019;14(3):e0213827
During the past few decades, there has been a nationwide push to improve performance and persistence outcomes for STEM undergraduates. As part of this effort, recent research has emphasized the need for focus on not only improving the delivery of course content, but also addressing the social-psychological needs of students. One promising intervention type that has been proposed as a multifaceted way to address both cognitive and social-psychological aspects of the learning process is the learning community. Learning communities provide students with opportunities to build a strong support system in college and are generally associated with increased student engagement and integration with campus systems and cultures. In this study, we examine the impact of a learning community intervention for first-year biological sciences majors, the Enhanced Academic Success Experience (EASE) program. Incoming freshmen are assigned to EASE based on their SAT (or ACT equivalent) Math score, a metric demonstrated to be a key predictor of student success in the program. We find that enrollment in EASE is correlated with higher STEM course grades; an increase of 0.25 (on a 0-4 point scale) in cumulative first-year GPA; and gains in non-academic outcomes, such as measures of sense of belonging and academic integration. Further, these outcomes are more pronounced for particular subgroup populations. For example, whereas surveyed male students seemed to benefit academically from participating in a learning community, female students reported a greater sense of belonging in regard to the biological sciences major and reported higher values for behavioral indicators of academic integration. Lastly, we find that the EASE program is positively correlated with students' intention to stay in the biological sciences major. And, among the three race-oriented groups, this impact is most pronounced for under-represented students. In light of these findings, we discuss the potential of discipline-specific learning community programs to improve academic outcomes for students most at risk of leaving STEM majors, such as students underprepared for college level coursework.
PMID: 30901339

Salem BE,Brecht ML,Ekstrand ML,Faucette M,Nyamathi AM
Correlates of physical, psychological, and social frailty among formerly incarcerated, homeless women.
Health Care Women Int. 2019 Mar 22;:1-25
Frailty is a deficit accumulation in physical, psychological and social domains. Correlates of frailty were explored among formerly incarcerated, homeless women (N?=?130, M = 38.9). Significant correlates of physical frailty were age, years homeless, prior violence, witnessing less violence, drug dependence, PTSD symptoms and tangible support. Significant correlates of psychological frailty were age, years homeless, witnessed violence, jail time, divorced less, drug use/dependence, prison time, methamphetamine use, and bodily pain. Significant correlates of social frailty were drug use, emotional regulation, and daily alcohol use. Reentry interventions are needed for formerly incarcerated, homeless women who experience physical, psychological and social frailty.
PMID: 30901288

Scurich N,John RS
The dark figure of sexual recidivism.
Behav Sci Law. 2019 Mar 22;
Empirical studies of sexual offender recidivism have proliferated in recent decades. Virtually all of the studies define recidivism as a new legal charge or conviction for a sexual crime, and these studies tend to find recidivism rates of the order of 5-15% after 5 years and 10-25% after 10+ years. It is uncontroversial that such a definition of recidivism underestimates the true rate of sexual recidivism because most sexual crime is not reported to legal authorities, a principle known as the "dark figure of crime." To estimate the magnitude of the dark figure of sexual recidivism, this paper uses a probabilistic simulation approach in conjunction with the following: (i) victim self-report survey data about the rate of reporting sexual crime to legal authorities; (ii) offender self-report data about the number of victims per offender; and (iii) different assumptions about the chances of being convicted of a new sexual offense given that it is reported. Under any configuration of assumptions, the dark figure is substantial, and as a consequence the disparity between recidivism defined as a new legal charge or conviction for a sex crime and recidivism defined as actually committing a new sexual crime is large. These findings call into question the utility of recidivism studies that rely exclusively on official crime statistics to define sexual recidivism, and highlight the need for additional, long-term studies that use a variety of different measures to assess whether or not sexual recidivism has occurred.
PMID: 30900348

Tran CL,Parucha JM,Jegatheesan P,Lee HC
Delayed Cord Clamping and Umbilical Cord Milking among Infants in California Neonatal Intensive Care Units.
Am J Perinatol. 2019 Mar 21;
To assess the current practice of delayed cord clamping (DCC) and to determine patient and hospital factors that predict DCC.
PMID: 30900218

Azadi P,Khodabande A,Riazi Esfahani M,Ghassemi F,Aliabadi N
Bilateral choroidal osteoma associated with langerhans cell histiocytosis, a coincidence?
J Curr Ophthalmol. 2019 Mar;31(1):109-112
To describe a case of bilateral choroidal osteoma (CO) in a patient with a history of langerhans cell histiocytosis (LCH).
PMID: 30899858

Agrawal S,Khokhar A,Gupta S
Cytomegalovirus Colitis in Primary Hypogammaglobulinemia With Normal CD4+ T Cells: Deficiency of CMV-Specific CD8+ T Cells.
Front Immunol. 2019;10:399
CMV colitis has been reported in immunocompromized patients with severe deficiency of CD4+ T cells and T cell functions. In this study we present an extensive immunological analysis in a patient with primary hypogammaglobulinemia and CMV colitis who had normal numbers of CD3+T, CD4+T and CD8+T cells, and normal T cell proliferative responses to mitogens and recall antigens. Naïve (T), central (T), and effector (T) memory subsets of CD4+ and CD8+ T cells, Granzyme+ and Perforin+ CD8+ T cells, PD-1+ T cells, CD4 Treg, CD8 Treg, and CMV tetramer specific CD8+ T cells were analyzed with specific antibodies and isotype controls using multicolor flow cytometry. CD8 T, Granzyme+ and Perforin+, and PD-1 CD8+T cells were increased, whereas CD8 T and CD8 T cells were decreased in the patient as compared to controls. CMV tetramer+ CD8+ T cells were decreased in the patient. These data demonstrate that a deficiency of CMV-specific CD8+ T cells even in the presence of normal CD4+ T cell numbers and normal T cell functions may predispose patients with primary hypogammaglobulinemia to CMV colitis.
PMID: 30899266

Horwitz AG,Smith DL,Held P,Zalta AK
Characteristics of Veteran and Civilian Suicide Decedents: A Sex-Stratified Analysis.
Am J Prev Med. 2019 Mar 18;
Few studies have examined characteristics distinguishing Veteran and civilian suicide decedents. An understanding of unique risk factors for Veteran suicide is critical to develop effective preventive interventions. This is particularly imperative for female Veterans, who have near double the suicide mortality rate of same-aged female civilians. The objectives of this study were to examine whether Veteran and civilian suicide decedents differed on risk factors and suicide-event characteristics, and to determine whether predictors changed based on sex.
PMID: 30898537

Fujita Y,Tinoco R,Li Y,Senft D,Ronai ZA
Ubiquitin Ligases in Cancer Immunotherapy - Balancing Antitumor and Autoimmunity.
Trends Mol Med. 2019 Mar 18;
Considerable progress has been made in understanding the contribution of E3 ubiquitin ligases to health and disease, including the pathogenesis of immunological disorders. Ubiquitin ligases exert exquisite spatial and temporal control over protein stability and function, and are thus crucial for the regulation of both innate and adaptive immunity. Given that immune responses can be both detrimental (autoimmunity) and beneficial (antitumor immunity), it is vital to understand how ubiquitin ligases maintain immunological homeostasis. Such knowledge could reveal novel mechanisms underlying immune regulation and identify new therapeutic approaches to enhance antitumor immunity and safeguard against autoimmunity.
PMID: 30898473

Delaplain PT,Harting MT,Jancelewicz T,Zhang L,Yu PT,Di Nardo M,Chen Y,Stein JE,Ford HR,Nguyen DV,Guner Y
Potential survival benefit with repair of congenital diaphragmatic hernia (CDH) after extracorporeal membrane oxygenation (ECMO) in select patients: Study by ELSO CDH Interest Group.
J Pediatr Surg. 2019 Mar 01;
Studying the timing of repair in CDH is prone to confounding factors, including variability in disease severity and management. We hypothesized that delaying repair until post-ECMO would confer a survival benefit.
PMID: 30898399

Balaguer FA,Mühlethaler T,Estévez-Gallego J,Calvo E,Giménez-Abián JF,Risinger AL,Sorensen EJ,Vanderwal CD,Altmann KH,Mooberry SL,Steinmetz MO,Oliva MÁ,Prota AE,Díaz JF
Crystal Structure of the Cyclostreptin-Tubulin Adduct: Implications for Tubulin Activation by Taxane-Site Ligands.
Int J Mol Sci. 2019 Mar 20;20(6)
It has been proposed that one of the mechanisms of taxane-site ligand-mediated tubulin activation is modulation of the structure of a switch element (the M-loop) from a disordered form in dimeric tubulin to a folded helical structure in microtubules. Here, we used covalent taxane-site ligands, including cyclostreptin, to gain further insight into this mechanism. The crystal structure of cyclostreptin-bound tubulin reveals covalent binding to ßHis229, but no stabilization of the M-loop. The capacity of cyclostreptin to induce microtubule assembly compared to other covalent taxane-site agents demonstrates that the induction of tubulin assembly is not strictly dependent on M-loop stabilization. We further demonstrate that most covalent taxane-site ligands are able to partially overcome drug resistance mediated by ßIII-tubulin (ßIII) overexpression in HeLa cells, and compare their activities to pironetin, an interfacial covalent inhibitor of tubulin assembly that displays invariant growth inhibition in these cells. Our findings suggest a relationship between a diminished interaction of taxane-site ligands with ßIII-tubulin and ßIII tubulin-mediated drug resistance. This supports the idea that overexpression of ßIII increases microtubule dynamicity by counteracting the enhanced microtubule stability promoted by covalent taxane-site binding ligands.
PMID: 30897704

Barr T,Lewis SA,Sureshchandra S,Doratt B,Grant KA,Messaoudi I
Chronic ethanol consumption alters lamina propria leukocyte response to stimulation in a region-dependent manner.
FASEB J. 2019 Mar 21;:fj201802780R
Chronic heavy alcohol consumption, also referred to as chronic heavy drinking (CHD), results in intestinal injury characterized by increased permeability, dysbiosis, nutrient malabsorption, potentially higher susceptibility to infection, and increased risk of colorectal cancer. However, our understanding of the mechanisms by which CHD results in intestinal damage remains incomplete. Here, we investigated the impact of chronic drinking on transcriptional and functional responses of lamina propria leukocytes (LPLs) isolated from the 4 major gut sections. Although no significant differences were detected between LPLs isolated from the ethanol and control groups at resting state within each major gut section, our analysis uncovered key regional differences in composition and function of LPLs independent of alcohol consumption. However, in response to phorbol myristate acetate and ionomycin, duodenal LPLs from ethanol-drinking animals generated a dampened response, whereas jejunal and ileal LPLs from ethanol-drinking animals produced a heightened response. Transcriptional responses following stimulation were pronounced in ileal and duodenal LPLs from the ethanol-drinking group but less evident in jejunal and colonic LPLs compared with controls, suggesting a more significant impact of alcohol on these gut regions. The altered intestinal LPL function detected in our study reveals remarkable region specificity and novel insight into potential mechanisms of intestinal injury associated with CHD.-Barr, T., Lewis, S. A., Sureshchandra, S., Doratt, B., Grant, K. A., Messaoudi, I. Chronic ethanol consumption alters lamina propria leukocyte response to stimulation in a region-dependent manner.
PMID: 30897342

Stuver RN,Khan N,Schwartz M,Acosta M,Federico M,Gisselbrecht C,Horwitz SM,Lansigan F,Pinter-Brown LC,Pro B,Shustov AR,Foss FM,Jain S
Single Agents Versus Combination Chemotherapy in Relapsed and Refractory Peripheral T-cell Lymphoma: Results from the Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE) Registry.
Am J Hematol. 2019 Mar 21;
Single agents have demonstrated activity in relapsed and refractory (R/R) peripheral T-cell lymphoma (PTCL). Their benefit relative to combination chemotherapy remains undefined.
PMID: 30896890

Kwasny MJ,Schueller SM,Lattie E,Gray EL,Mohr DC
Exploring the Use of Multiple Mental Health Apps Within a Platform: Secondary Analysis of the IntelliCare Field Trial.
JMIR Ment Health. 2019 Mar 21;6(3):e11572
IntelliCare is a mental health app platform with 14 apps that are elemental, simple and brief to use, and eclectic. Although a variety of apps may improve engagement, leading to better outcomes, they may require navigation aids such as recommender systems that can quickly direct a person to a useful app.
PMID: 30896433

Basile G,Breda A,Gomez Rivas J,Cacciamani G,Okhunov Z,Dourado A,Rodriguez Socarras M,Sgro' E,Cozzupoli P,Veneziano D
Comparison between Near-infrared fluorescence imaging with indocyanine green and InfraRed imaging: on-bench trial for kidney perfusion analysis. A project by ESUT-YAUWP group.
Minerva Urol Nefrol. 2019 Mar 18;
Infrared thermography (IRT) imaging technology is able to measure surface temperatures in real-time. The aim of our study is to understand whether IRT imaging is a reliable technology for the assessment of kidney-parenchyma perfusion with warm fluids.
PMID: 30895767

Tran C,Bennett MV,Gould JB,Lee HC,Lanzieri TM
Cytomegalovirus Infection among Infants in Neonatal Intensive Care Units, California, 2005 to 2016.
Am J Perinatol. 2019 Mar 20;
The main purpose of this article is to assess trends in cytomegalovirus (CMV) infection reported among infants in California neonatal intensive care units (NICUs) during 2005 to 2016.
PMID: 30895580

Wong ND,Shapiro MD
Interpreting the Findings From the Recent PCSK9 Monoclonal Antibody Cardiovascular Outcomes Trials.
Front Cardiovasc Med. 2019;6:14
The recent development of monoclonal antibodies targeted to proprotein convertase subtilisin/kexin type 9 (PCSK9), e.g., PCSK9 inhibitors has revolutionized the landscape of lipid management. Many clinical trials assessing this class have demonstrated remarkable and consistent reductions in low-density lipoprotein-cholesterol. Moreover, the GLAGOV trial demonstrated the efficacy of evolocumab, when added to statin therapy, in reducing the progression of atherosclerosis measured by serial intravascular ultrasound, with the first suggestion of continued benefit down to LDL-C levels of 0.5 mmol/L (20 mg/dL). This trial was followed by the FOURIER Cardiovascular Outcomes trial in more than 27,000 patients with stable atherosclerotic cardiovascular disease (ASCVD) where evolocumab reduced the primary endpoint of atherosclerotic events by 15%, without significant safety differences between treatment groups. Furthermore, subgroup analyses suggested greater benefits seen in those with longer exposure to evolocumab recent acute coronary syndrome, multiple myocardial infarctions, multivessel coronary artery disease, peripheral arterial disease, as well as the subgroup who achieved very low low-density lipoprotein-cholesterol levels of below 0.3 mmol/L (10 mg/dL). Moreover, the EBBINGHAUS substudy demonstrated no differences in objectively measured cognitive function between treatment groups. The SPIRE 2 trial evaluating bococizumab in high-risk patients with baseline LDL-C ≥2.6 mmol/L (100 mg/dL) demonstrated significant atherosclerotic risk reduction, but the trial and further development of the drug was prematurely discontinued due to substantial attenuation of the LDL-C effect over time due to the development of neutralizing antibodies. Finally, the ODYSSEY Cardiovascular Outcomes trial testing alirocumab in subjects with recent (
PMID: 30895178

Zhou AE,Berry AA,Bailey JA,Pike A,Dara A,Agrawal S,Stucke EM,Ouattara A,Coulibaly D,Lyke KE,Laurens MB,Adams M,Takala-Harrison S,Pablo J,Jasinskas A,Nakajima R,Niangaly A,Kouriba B,Kone AK,Rowe JA,Doumbo OK,Thera MA,Patel JJ,Tan JC,Felgner PL,Plowe CV,Travassos MA
Antibodies to Peptides in Semiconserved Domains of RIFINs and STEVORs Correlate with Malaria Exposure.
mSphere. 2019 Mar 20;4(2)
The repetitive interspersed family (RIFIN) and the subtelomeric variable open reading frame (STEVOR) family represent two of three major variant surface antigen families involved in malaria pathogenesis and immune evasion and are potential targets in the development of natural immunity. Protein and peptide microarrays populated with RIFINs and STEVORs associated with severe malaria vulnerability in Malian children were probed with adult and pediatric sera to identify epitopes that reflect malaria exposure. Adult sera recognized and reacted with greater intensity to all STEVOR proteins than pediatric sera did. Serorecognition of and seroreactivity to peptides within the semiconserved domain of STEVORs increased with age and seasonal malaria exposure, while serorecognition and seroreactivity increased for the semiconserved and second hypervariable domains of RIFINs only with age. Serologic responses to RIFIN and STEVOR peptides within the semiconserved domains may play a role in natural immunity to severe malaria. Malaria, an infectious disease caused by the parasite , causes nearly 435,000 deaths annually worldwide. RIFINs and STEVORs are two variant surface antigen families that are involved in malaria pathogenesis and immune evasion. Recent work has shown that a lack of humoral immunity to these proteins is associated with severe malaria vulnerability in Malian children. This is the first study to have compared serologic responses of children and adults to RIFINs and STEVORs in settings of malaria endemicity and to examine such serologic responses before and after a clinical malaria episode. Using microarrays, we determined that the semiconserved domains in these two parasite variant surface antigen families harbor peptides whose seroreactivity reflects malaria exposure. A similar approach has the potential to illuminate the role of variant surface antigens in the development of natural immunity to clinical malaria. Potential vaccines for severe malaria should include consideration of peptides within the semiconserved domains of RIFINs and STEVORs.
PMID: 30894432

Randall LM,Birrer MJ,Herzog TJ
Ovarian Cancer Maintenance: Practice-Changing Data Calls for Changing Practice.
Oncologist. 2019 Mar 20;
PMID: 30894410

von Ehrenstein OS,Ling C,Cui X,Cockburn M,Park AS,Yu F,Wu J,Ritz B
Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study.
BMJ. 2019 Mar 20;364:l962
To examine associations between early developmental exposure to ambient pesticides and autism spectrum disorder.
PMID: 30894343

Modrak M,Sundem L,Gupta R,Zuscik MJ,Elfar J
Pharmacological Attenuation of Electrical Effects in a Model of Compression Neuropathy.
J Bone Joint Surg Am. 2019 Mar 20;101(6):523-530
Peripheral nerve compression and entrapment can be debilitating. Using a validated animal model of peripheral nerve compression, we examined the utility of 2 drugs approved for other uses in humans, 4-aminopyridine (4-AP) and erythropoietin (EPO), as treatments for surgically induced ischemia and as adjuvants to surgical decompression.
PMID: 30893233

Wang JV,Hazan E,Rohrer T,Zachary CB,Saedi N
Fellowship Selection Criteria for Procedural and Cosmetic Dermatology.
Dermatol Surg. 2019 Mar 15;
PMID: 30893179

Ekelem C,Thomas L,Van Hal M,Valdebran M,Lotfizadeh A,Mlynek K,Mesinkovska NA
Radiofrequency Therapy and Noncosmetic Cutaneous Conditions.
Dermatol Surg. 2019 Mar 18;
The need for noninvasive methods in treatment of cutaneous disease has continued to evolve exponentially. Amidst the search for technologies, radiofrequency (RF) has proven efficacious in numerous skin disease processes. Although RF is well known for its cosmetic utility, its mechanism is valued in the treatment of many noncosmetic cutaneous conditions of various etiologies.
PMID: 30893163

Beer KR,Shamban AT,Avelar RL,Gross JE,Jonker A
Efficacy and Safety of PrabotulinumtoxinA for the Treatment of Glabellar Lines in Adult Subjects: Results From 2 Identical Phase III Studies.
Dermatol Surg. 2019 Mar 18;
PrabotulinumtoxinA is a 900-kDa botulinum toxin Type A produced by Clostridium botulinum.
PMID: 30893162

Kaufman J,Cohen JL,Peredo MI,Jonas B,Down R,Nogueira A
Clinical Assessment of 2 Licensed AbobotulinumtoxinA Injection Volumes for the Treatment of Glabellar Lines.
Dermatol Surg. 2019 Mar 18;
Two licensed reconstitution volumes may be used to achieve the recommended abobotulinumtoxinA (ABO) dose for glabellar line correction.
PMID: 30893159

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