Challenges in the analysis of pharmaceutical lentiviral vector products by orthogonal and complementary physical (nano)particle characterization techniques.

Lentiviral vectors (LVVs) are used as a starting material to generate chimeric antigen receptor (CAR) T cells. Therefore, LVVs need to be carefully analyzed to ensure safety, quality, and potency of the final product. We evaluated orthogonal and complementary analytical techniques for their suitability to characterize particulate matter (impurities and LVVs) in pharmaceutical LVV materials at development stage derived from suspension and adherent manufacturing processes.

Enzymatic detection of α-hydroxybutyrate, an important marker of insulin resistance, and comparison with LC-MS/MS detection.

Aim: The metabolite α-hydroxybutyrate (α-HB) is an important marker of insulin resistance and impaired glucose tolerance allowing to identify patients at risk of developing diabetes and related metabolic disorders before any symptoms become apparent. At present, its exact quantification requires mass spectrometry (LC-MS), which is not compatible with routine laboratory use. Accordingly, a simple enzymatic-based method was assessed and its applicability and measuring accuracy compared with LC-MS was investigated.

Locating Medical Information during an Infodemic: Information Seeking Behavior and Strategies of Health-Care Workers in Germany.

Background: The COVID-19 pandemic has led to a flood of-often contradictory-evidence. HCWs had to develop strategies to locate information that supported their work. We investigated the information-seeking of different HCW groups in Germany.

SUMO Modification of Hepatitis B Virus Core Mediates Nuclear Entry, Promyelocytic Leukemia Nuclear Body Association, and Efficient Formation of Covalently Closed Circular DNA.

Persistence of hepatitis B virus (HBV) infection is due to a nuclear covalently closed circular DNA (cccDNA), generated from the virion-borne relaxed circular DNA (rcDNA) genome in a process likely involving numerous cell factors from the host DNA damage response (DDR). The HBV core protein mediates rcDNA transport to the nucleus and likely affects stability and transcriptional activity of cccDNA. Our study aimed at investigating the role of HBV core protein and its posttranslational modification (PTM) with SUMO (small ubiquitin-like modifiers) during the establishment of cccDNA.

Cytotoxic CNS-associated T cells drive axon degeneration by targeting perturbed oligodendrocytes in mutant mice.

Myelin defects lead to neurological dysfunction in various diseases and in normal aging. Chronic neuroinflammation often contributes to axon-myelin damage in these conditions and can be initiated and/or sustained by perturbed myelinating glia. We have previously shown that distinct mutations result in neurodegeneration that is largely driven by adaptive immune cells.

Apobec3A Deamination Functions Are Involved in Antagonizing Efficient Human Adenovirus Replication and Gene Expression.

Apobec3A is involved in the antiviral host defense, targeting nuclear DNA, introducing point mutations, and thereby activating DNA damage response (DDR). Here, we found a significant upregulation of Apobec3A during HAdV infection, including Apobec3A protein stabilization mediated by the viral proteins E1B-55K and E4orf6, which subsequently limited HAdV replication and most likely involved a deaminase-dependent mechanism. The transient silencing of Apobec3A enhanced adenoviral replication.

The Gendered Work/Role of Program Directors in International Graduate Medical Education.

Healthcare organizations offer numerous clinical and academic leadership pathways for physicians, among which the position of program director (PD) is considered to be a prominent educational leadership role. As PDs are instrumental in the recruitment and training of the next generations of physicians, PD gender distribution can affect the present and future of a medical specialty. This study offers a dialectical perspective in understanding how international PDs negotiate gendered understanding of their work/role by using the framework of Relational Dialectics Theory 2.

Mortality prediction of retinal vessel diameters and function in a long-term follow-up of haemodialysis patients.

Aim: Retinal vessel diameters are candidate biomarkers of mortality prediction in large population-based studies. We aimed to investigate the predictive value of retinal vessel diameters and flicker-induced retinal arteriolar and venular dilation on all-cause mortality in long-term follow-up of haemodialysis patients.

Methods And Results: Retinal vessel diameters as well as maximum arteriolar (aMax) and venular dilation (vMax) were investigated in 275 and 214 haemodialysis patients, respectively.

Tantalum Oxide as an Efficient Alternative Electron Transporting Layer for Perovskite Solar Cells.

Electron transporting layers facilitating electron extraction and suppressing hole recombination at the cathode are crucial components in any thin-film solar cell geometry, including that of metal-halide perovskite solar cells. Amorphous tantalum oxide (TaO) deposited by spin coating was explored as an electron transport material for perovskite solar cells, achieving power conversion efficiency (PCE) up to ~14%. Ultraviolet photoelectron spectroscopy (UPS) measurements revealed that the extraction of photogenerated electrons is facilitated due to proper alignment of bandgap energies.

Montelukast is a dual-purpose inhibitor of SARS-CoV-2 infection and virus-induced IL-6 expression identified by structure-based drug repurposing.

Drug-repurposing has been instrumental to identify drugs preventing SARS-CoV-2 replication or attenuating the disease course of COVID-19. Here, we identify through structure-based drug-repurposing a dual-purpose inhibitor of SARS-CoV-2 infection and of IL-6 production by immune cells. We created a computational structure model of the receptor binding domain (RBD) of the SARS-CoV-2 spike 1 protein, and used this model for screening against a library of 6171 molecularly defined binding-sites from drug molecules.

Recognizing Gender Parity in Military Medicine: An Analysis of Plenary Speakers and Award Recipients at Military American College of Physicians Chapter Meetings.

Introduction: Despite the advances toward gender parity in medicine, a gap exists in the recognition of women physicians at academic and subspecialty medical conferences as plenary speakers and award winners. Conferences are cornerstones in the practice of medicine because they serve as platforms to showcase physicians' successes and disseminate work. The selection of who is honored at such events can impact an individual's career by creating networks that may lead to future opportunities.

Particles in Biopharmaceutical Formulations, Part 2: An Update on Analytical Techniques and Applications for Therapeutic Proteins, Viruses, Vaccines and Cells.

Particles in biopharmaceutical formulations remain a hot topic in drug product development. With new product classes emerging it is crucial to discriminate particulate active pharmaceutical ingredients from particulate impurities. Technical improvements, new analytical developments and emerging tools (e.

"I Find It Quite a Privilege to Be Involved in Their Lives": A Multinational Qualitative Study of Program Directors' Perspectives on Their Relationships with Residents.

Phenomenon: Program director PD)-resident relationships are important in shaping resident experiences and educational outcomes. Yet, there is limited literature on the development or meaning of these relationships, particularly from the PD perspective. Through qualitative interviews, we explore how PDs navigate their role to develop and maintain relationships with their trainees, and elucidate how these relationships impact the PDs personally and professionally.

International Residency Program Directors on Implementing Educational Transformation: A Qualitative Study of Their Experiences and Strategies for Overcoming Challenges.

Background: Residency program directors (PDs) need to navigate diverse roles and responsibilities as clinical teachers, administrators, and drivers of educational improvement. Little is known about the experience of PDs leading transformation of international residency programs.

Objective: We explored the lived experiences of international residency PDs and developed an understanding of how PDs manage educational program transformation.

Exaggerated ventilatory drive estimates from epiglottic and esophageal pressure deflections in the presence of airway occlusion.

Esophageal and epiglottic pressure deflections are widely used to quantify ventilatory effort during sleep in patients with obstructive sleep apnea (OSA). However, changes in upper airway patency will fundamentally alter pressure gradients across the respiratory system with different airflow and volume-dependent effects on esophageal versus epiglottic pressure. The magnitude of these obstruction effects on ventilatory effort assessed from pressure deflections has not been systematically investigated.

Weight management counseling experiences of first year medical students before starting medical school and their self-perceived impact on treating patients with obesity.

Physicians can play a vital role in counseling patients on overweight and obesity. This secondary analysis examined whether experiences in patient care specific to weight management before starting medical school were associated with students' intentions and confidence to provide weight management counseling (WMC) to patients who have overweight or obesity, and perceived impact as future physicians on patients' motivation to manage weight. First-year medical students (n = 1305) in the entering class of 2020 at eight medical schools nationwide completed questions relating to their prior experiences in patient care and WMC using the 5As.

Interferon-induced degradation of the persistent hepatitis B virus cccDNA form depends on ISG20.

Hepatitis B virus (HBV) persists by depositing a covalently closed circular DNA (cccDNA) in the nucleus of infected cells that cannot be targeted by available antivirals. Interferons can diminish HBV cccDNA via APOBEC3-mediated deamination. Here, we show that overexpression of APOBEC3A alone is not sufficient to reduce HBV cccDNA that requires additional treatment of cells with interferon indicating involvement of an interferon-stimulated gene (ISG) in cccDNA degradation.

Teaching Medical Students to Help Patients Manage Their Weight: Outcomes of an Eight-School Randomized Controlled Trial.

Background: Given the rising rates of obesity there is a pressing need for medical schools to better prepare students for intervening with patients who have overweight or obesity and for prevention efforts.

Objective: To assess the effect of a multi-modal weight management curriculum on counseling skills for health behavior change.

Design: A pair-matched, group-randomized controlled trial (2015-2020) included students enrolled in eight U.

Leveraging Online Learning to Promote Systems Thinking for Sustainable Food Systems Training in Dietetics Education.

Educating and training a multisectoral food systems workforce is a critical part of developing sustainable, resilient, and healthy food and water systems. This paper shares perspectives from a working group of educators, learners, and food systems subject matter experts that collaborated over the course of a year to develop, pilot test, and evaluate two interactive webinar series with a multi-site cohort of dietetics interns and graduate students. The three-part webinar series format included a training webinar, a practice activity, and a synthesis webinar.

Molecular Level Synthesis of InFeO and InFeO/FeO Nanocomposites.

New heterometallic In-Fe alkoxides [InFe(OBu)(PyTFP)] (), [InFe(OPen)(Py)] (), and [InFe(OPen)] () were synthesized and structurally characterized. The arrangement of metal centers in mixed-metal framework was governed by the In:Fe ratio and the coordination preferences of Fe(III) and In(III) centers to be in tetrahedral and octahedral environments, respectively. displayed a star-shaped so-called "Mitsubishi" motif with the central In atom coordinated with three tetrahedral {Fe(OPen)} anionic units.