Biobehavioral effects of Tai Chi Qigong in men with prostate cancer: Study design of a three-arm randomized clinical trial.

Fatigue is often one of the most commonly reported symptoms in prostate cancer survivors, but it is also one of the least understood cancer-related symptoms. Fatigue is associated with psychological distress, disruptions in sleep quality, and impairments in health-related quality of life. Moreover, inflammatory processes and changes related to the hypothalamic-pituitary-adrenal (HPA) axis and/or autonomic nervous system may also play a role in cancer-related fatigue. Thus, effective treatments for fatigue in prostate cancer survivors represent a current unmet need. Prior research has shown that Tai Chi Qigong, a mind-body exercise intervention, can improve physical and emotional health. Herein, we describe the protocol of the ongoing 3-arm randomized controlled Health Empowerment & Recovery Outcomes (HERO) clincal trial. One hundred sixty-six prostate cancer survivors with fatigue are randomized to a modified Tai Chi Qigong intervention (TCQ), intensity-matched body training intervention (BT), or usual care (UC) condition. Guided by biopsychosocial and psychoneuroimmunology models, we propose that TCQ, as compared to BT or UC will: i) reduce fatigue (primary outcome) in prostate cancer survivors; ii) reduce inflammation; and iii) regulate the expression of genes from two major functional clusters: a) inflammation, vasodilation and metabolite sensing and b) energy and adrenergic activation. Assessments are conducted at baseline, the 6-week midpoint of the intervention, and 1 week, 3 months, and 12 months post-intervention. If our findings show that TCQ promotes recovery from prostate cancer and its treatment, this type of intervention can be integrated into survivorship care plans as the standard of care. The study's findings will also provide novel information about underlying biobehavioral mechanisms of cancer-related fatigue. Trial registration number:NCT03326713; clinicaltrials.gov

Probing pre-supernova mass loss in double-peaked Type Ibc supernovae from the Zwicky Transient Facility

Eruptive mass loss of massive stars prior to supernova (SN) explosion is key to understanding their evolution and end fate. An observational signature of pre-SN mass loss is the detection of an early, short-lived peak prior to the radioactive-powered peak in the lightcurve of the SN. This is usually attributed to the SN shock passing through an extended envelope or circumstellar medium (CSM). Such an early peak is common for double-peaked Type IIb SNe with an extended Hydrogen envelope but is uncommon for normal Type Ibc SNe with very compact progenitors. In this paper, we systematically study a sample of 14 double-peaked Type Ibc SNe out of 475 Type Ibc SNe detected by the Zwicky Transient Facility. The rate of these events is ~ 3-9 % of Type Ibc SNe. A strong correlation is seen between the peak brightness of the first and the second peak. We perform a holistic analysis of this sample's photometric and spectroscopic properties. We find that six SNe have ejecta mass less than 1.5 Msun. Based on the nebular spectra and lightcurve properties, we estimate that the progenitor masses for these are less than ~ 12 Msun. The rest have an ejecta mass > 2.4 Msun and a higher progenitor mass. This sample suggests that the SNe with low progenitor masses undergo late-time binary mass transfer. Meanwhile, the SNe with higher progenitor masses are consistent with wave-driven mass loss or pulsation-pair instability-driven mass loss simulations.Comment: Submitted to ApJ. Comments are welcome. arXiv admin note: text overlap with arXiv:2210.0572

InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma

We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids’ quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.Medicin

Gerontological research in China: The role of anthropological inquiry

One fifth of the world's elderly population lives in China. Until recently political restrictions have hindered the conduct of research particularly ethnography. This piece provides an overview of recent research findings by Western scholars and of ethnographic research in progress in the areas of demography, state policy, age stratification, family planning, residence patterns, inter-generational transfers, patrilineality, health, illness, long term care, social welfare, and mortuary ritual. It analyzes the potential contributions of ethnography in this area.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42988/1/10823_2004_Article_BF00119706.pd

Assessment of software methods for estimating protein-protein relative binding affinities.

A growing number of computational tools have been developed to accurately and rapidly predict the impact of amino acid mutations on protein-protein relative binding affinities. Such tools have many applications, for example, designing new drugs and studying evolutionary mechanisms. In the search for accuracy, many of these methods employ expensive yet rigorous molecular dynamics simulations. By contrast, non-rigorous methods use less exhaustive statistical mechanics, allowing for more efficient calculations. However, it is unclear if such methods retain enough accuracy to replace rigorous methods in binding affinity calculations. This trade-off between accuracy and computational expense makes it difficult to determine the best method for a particular system or study. Here, eight non-rigorous computational methods were assessed using eight antibody-antigen and eight non-antibody-antigen complexes for their ability to accurately predict relative binding affinities (ΔΔG) for 654 single mutations. In addition to assessing accuracy, we analyzed the CPU cost and performance for each method using a variety of physico-chemical structural features. This allowed us to posit scenarios in which each method may be best utilized. Most methods performed worse when applied to antibody-antigen complexes compared to non-antibody-antigen complexes. Rosetta-based JayZ and EasyE methods classified mutations as destabilizing (ΔΔG < -0.5 kcal/mol) with high (83-98%) accuracy and a relatively low computational cost for non-antibody-antigen complexes. Some of the most accurate results for antibody-antigen systems came from combining molecular dynamics with FoldX with a correlation coefficient (r) of 0.46, but this was also the most computationally expensive method. Overall, our results suggest these methods can be used to quickly and accurately predict stabilizing versus destabilizing mutations but are less accurate at predicting actual binding affinities. This study highlights the need for continued development of reliable, accessible, and reproducible methods for predicting binding affinities in antibody-antigen proteins and provides a recipe for using current methods

Protective mechanisms of nonneutralizing antiviral antibodies.

Antibodies that can bind to viruses but are unable to block infection in cell culture are known as "nonneutralizing antibodies." Such antibodies are nearly universally elicited following viral infection and have been characterized in viral infections such as influenza, rotavirus, cytomegalovirus, HIV, and SARS-CoV-2. It has been widely assumed that these nonneutralizing antibodies do not function in a protective way in vivo and therefore are not desirable targets of antiviral interventions; however, increasing evidence now shows this not to be true. Several virus-specific nonneutralizing antibody responses have been correlated with protection in human studies and also shown to significantly reduce virus replication in animal models. The mechanisms by which many of these antibodies function is only now coming to light. While nonneutralizing antibodies cannot prevent viruses entering their host cell, nonneutralizing antibodies work in the extracellular space to recruit effector proteins or cells that can destroy the antibody-virus complex. Other nonneutralizing antibodies exert their effects inside cells, either by blocking the virus life cycle directly or by recruiting the intracellular Fc receptor TRIM21. In this review, we will discuss the multitude of ways in which nonneutralizing antibodies function against a range of viral infections

nNAb-mediated antiviral effector functions following antigen binding to Fab.

NK cells can exhibit ADCC by detecting target cells (i.e., virus-infected cells) opsonized by antibodies via the FcγRIII (CD16) receptor and induce apoptosis by releasing cytotoxic granules. Macrophages and other phagocytes perform ADCP by recognizing opsonized viral particles via the FcγRI (CD64) and FcγRIIA (CD32) receptors leading to virolysis and downstream antigen presentation of viral antigen. Antibodies activate the classical complement pathway after binding to the soluble complement complex, C1q. In addition to viral aggregation and opsonization, antibody-dependent complement fixation on viral or target cell membranes can lead to the formation of the pore-forming MAC and ADCML. Cooperation between nNAb (green) binding that exposes epitopes for neutralizing antibody (yellow) binding can enhance the efficacy of virus neutralization. Antibodies can block viral replication intracellularly; for dsRNA viruses that maintain an intact innermost capsid inside cells, antibodies can block mRNA egress. Intracellular antibodies can also be bound by TRIM21, which leads to proteasomal degradation of the virus–antibody complex and can result in enhanced MHC class I antigen presentation. Created with Biorender.com. ADCC, antibody-dependent cellular cytotoxicity; ADCML, antibody-dependent complement-mediated lysis; ADCP, antibody-dependent cellular phagocytosis; MAC, membrane attack complex; NK, natural killer; nNAb, nonneutralizing antibody.</p

Viruses experimentally proven to be protected against by monoclonal nNAbs.

The studies included were all performed by passive transfer of antibody and virus challenge in animal models, and each represents the first report for each virus type.</p

Epidemiology and SARS-CoV-2 Infection Patterns among Youth Followed at a Large Los Angeles Health Network during 2020–2022: Clinical Presentation, Prevalent Strains, and Correlates of Disease Severity

Background: Outcomes of SARS CoV-2 infection in infants, children and young adults are reported less frequently than in older populations. The evolution of SARS-CoV-2 cases in LA County youths followed at a large health network in southern California over two years was evaluated. Methods: A prospective cohort study of patients aged 0–24 years diagnosed with COVID-19 was conducted. Demographics, age distribution, disease severity, circulating variants of concern (VOCs), and immunization rates were compared between first and second pandemic years. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) of factors associated with severe/critical COVID-19. Results: In total, 61,208 patients 0–24 years of age were tested for SARS-CoV-2 by polymerase chain reaction (PCR); 5263 positive patients (8.6%) with available data were identified between March 2020 and March 2022. In Year 1, 5.8% (1622/28,088) of youths tested positive, compared to 11% (3641/33,120) in Year 2 (p 12% across all age groups in the second half of Year 2, when Omicron prevailed. Pulmonary disease was associated with higher risk of severe COVID-19 in both years (OR: 2.4, 95% CI: 1.4–4.3, p = 0.002, Year 1; OR: 11.3, 95% CI: 4.3–29.6, Year 2, p p < 0.05). Conclusions: Despite different VOCs and higher rates of test positivity in Year 2 compared to Year 1, most youths with COVID-19 had asymptomatic/mild disease. Underlying pulmonary conditions increased the risk of severe COVID-19, while vaccination was highly protective against severe disease in youths