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Abstract Background Residual disease following cytoreductive surgery in patients with ovarian cancer has been associated with poorer survival outcomes compared with no residual disease. We performed a meta-analysis to assess the impact of varying levels of residual disease status on survival outcomes in patients with ovarian cancer who have undergone primary cytoreductive surgery or interval cytoreductive surgery in the setting of new therapies for this disease. Methods Medline, Embase, and Cochrane databases (January 2011 – July 2020) and grey literature, bibliographic and key conference proceedings, were searched for eligible studies. Fixed and random-effects meta-analyses compared progression and survival by residual disease level across studies. Heterogeneity between comparisons was explored via type of surgery, disease stage, and type of adjuvant chemotherapy. Results Of 2832 database and 16 supplementary search articles screened, 50 studies were selected; most were observational studies. The meta-analysis showed that median progression-free survival and overall survival decreased progressively with increasing residual disease (residual disease categories of 0 cm, > 0–1 cm and > 1 cm). Compared with no residual disease, hazard ratios (HR) for disease progression increased with increasing residual disease category (1.75 [95% confidence interval: 1.42, 2.16] for residual disease > 0–1 cm and 2.14 [1.34, 3.39] for residual disease > 1 cm), and also for reduced survival (HR versus no residual disease, 1.75 [ 1.62, 1.90] for residual disease > 0–1 cm and 2.32 [1.97, 2.72] for residual disease > 1 cm). All comparisons were significant (p

Faith-based colleges and universities in America have historically been described as "church-related." Unfortunately, this classification is too one-dimensional, revealing virtually nothing about how faith-based identity influences the mission, rhetoric, curriculum, or policies of institutions. Although scholars have advanced sophisticated typologies of Protestant and Catholic institutions, we propose that we still need a new means of empirical analysis to determine the degree to which the faith identity of an institution influences important administrative, curricular, and co-curricular decisions. We then apply our Operationalizing Faith Identity Guide (OFIG) to Protestant institutions in the United States to demonstrate the helpfulness of its application.

Soft X-ray spectromicroscopy at the O K-edge, U N4,5-edges and Ce M4,5-edges has been performed on focused ion beam sections of spent nuclear fuel for the first time, yielding chemical information on the sub-micrometer scale. To analyze these data, a modification to non-negative matrix factorization (NMF) was developed, in which the data are no longer required to be non-negative, but the non-negativity of the spectral components and fit coefficients is largely preserved. The modified NMF method was utilized at the O K-edge to distinguish between two components, one present in the bulk of the sample similar to UO2 and one present at the interface of the sample which is a hyperstoichiometric UO2+x species. The species maps are consistent with a model of a thin layer of UO2+x over the entire sample, which is likely explained by oxidation after focused ion beam (FIB) sectioning. In addition to the uranium oxide bulk of the sample, Ce measurements were also performed to investigate the oxidation state of that fission product, which is the subject of considerable interest. Analysis of the Ce spectra shows that Ce is in a predominantly trivalent state, with a possible contribution from tetravalent Ce. Atom probe analysis was performed to provide confirmation of the presence and localization of Ce in the spent fuel.

Abstract Background Hypercholesterolemia is associated with tendon pathology, but the reasons underpinning this relationship are not well understood. Cholesterol can accumulate in the tendon non-collagenous matrix which may affect both global and local tissue mechanics. Changes to the local strain environment within tendon may have significant implications for mechanosensitive tenocytes. Here, we investigated the association between elevated blood cholesterol and presence of tendon lipids in the Achilles tendon. We expected lipids to be localised in the proteoglycan-rich inter-sub-tendon matrix (ISTM), therefore we also sought to examine the impact of this on the biomechanical and viscoelastic properties of the ISTM. Methods The Achilles tendons of 32 young wild-type (SD) and 32 apolipoprotein E knock-out rats (ApoE −/− ) were harvested at 15.6 ± 2.3 weeks of age. 32 specimens underwent histological examination to assess the distribution of lipids throughout sub-tendons and ISTM. The remaining specimens were prepared for biomechanical testing, where the ISTM between the gastrocnemius and soleus sub-tendons was subjected to shear load mechanical testing. A sub-set of tests were video recorded to enable a strain analysis. Results ApoE −/− serum cholesterol was double that of SD rats (mean 2.25 vs. 1.10 mg/ml, p

Objectives: The role of community in individuals' well-being has been extensively examined in the Western context. However, little is known about how the host community is related to sojourners' well-being in a crisis in an Asian context. The current study aims at exploring international students’ sense of community in the Chinese context under the direct threat of a global health crisis. Methods: Using a cross-sectional sample of 102 international students staying in Wuhan during the 76-day lockdown at the earliest stage of the COVID-19 pandemic, the current study explored the relationship between international students’ sense of community and anxiety, and the mediating role of social contact, social support from three key sources in the host community (host university, international students, and Chinese friends). Results: Results showed that participants’ stronger sense of community indirectly reduced anxiety via the role of sources of contact and support from the host community. Conclusions: This study provided further evidence to support the nurturance of the sense of community in community resilience and provided implications on how the host community can help to enhance sojourners’ psychological well-being in a global crisis.

Cytotoxic protein aggregation-induced impairment of cell function and homeostasis are hallmarks of age-related neurodegenerative pathologies. As proteasomal degradation represents the major clearance pathway for oxidatively damaged proteins, a detailed understanding of the molecular events underlying its stress response is critical for developing strategies to maintain cell viability and function. Although the 26S proteasome has been shown to disassemble during oxidative stress, its conformational dynamics remains unclear. To this end, we have developed a new quantitative cross-linking mass spectrometry (QXL-MS) workflow to explore the structural dynamics of proteasome complexes in response to oxidative stress. This strategy comprises SILAC-based metabolic labeling, HB tag-based affinity purification, a 2-step cross-linking reaction consisting of mild in vivo formaldehyde and on-bead DSSO cross-linking, and multi-stage tandem mass spectrometry (MSn) to identify and quantify cross-links. This integrated workflow has been successfully applied to explore the molecular events underlying oxidative stress-dependent proteasomal regulation by comparative analyses of proteasome complex topologies from treated and untreated cells. Our results show that H2O2 treatment weakens the 19S-20S interaction within the 26S proteasome, along with reorganizations within the 19S and 20S subcomplexes. Altogether, this work sheds light on the mechanistic response of the 26S to acute oxidative stress, suggesting an intermediate proteasomal state(s) before H2O2-mediated dissociation of the 26S. The QXL-MS strategy presented here can be applied to study conformational changes of other protein complexes under different physiological conditions.

Summary: Background: As opioid overdoses surge, medications for opioid use disorder (MOUD) remain underutilized. MOUD is rarely offered in correctional facilities although individuals involved in the criminal justice system have higher rates of OUD and mortality relative to the general population. Methods: A retrospective cohort design examined the effect of MOUD while incarcerated on 12 months post-release treatment engagement and retention, overdose mortality, and recidivism. Individuals (N = 1600) who participated in the Rhode Island Department of Corrections (RIDOC) MOUD program (the United States’ first statewide program) and were released from incarceration from December 1, 2016, to December 31, 2018, were included. The sample was 72.6% Male (27.4% female) and 80.8% White (5.8% Black, 11.4% Hispanic, 2.0% another race). Findings: 56% were prescribed methadone, 43% buprenorphine, and 1% naltrexone. During incarceration, 61% were continued on MOUD from the community, 30% were inducted onto MOUD upon incarceration, and 9% were inducted pre-release. At 30 days and 12 months post-release, 73% and 86% of participants engaged in MOUD treatment, respectively, and those newly inducted had lower post-release engagement than those who continued from the community. Reincarceration rates (52%) were similar to the general RIDOC population. Twelve overdose deaths occurred during the 12-month follow-up, with only one overdose death during the first two weeks post-release. Interpretations: Implementing MOUD in correctional facilities, with seamless linkage to community care is a needed life-saving strategy. Funding: Rhode Island General Fund, the NIH of Health HEAL Initiative, the NIGMS, and the NIDA.

Abstract Background Lateral wedge insoles (both standalone and those incorporating individualized arch support) have been frequently studied for the effects on knee joint loading and pain in people with knee osteoarthritis. It has been shown that many people who use these insoles do not obtain the intended biomechanical effect, and thus may not experience a clinical benefit. The ability to identify biomechanical responders to lateral wedge insoles before research or clinical intervention is an important objective for efficient resource use and optimizing patient outcomes. The purpose of our exploratory, hypothesis‐generating study was to provide an initial assessment of variables that are associated with the biomechanical response to lateral wedge insoles in people with knee osteoarthritis. Methods We collected a number of demographic (age, sex, body mass index, foot posture), clinical (knee pain, foot pain, radiographic disease severity), and walking‐related (speed, knee alignment, frontal plane subtalar movement, and foot rotation) outcomes from 53 individuals with painful, radiographically‐confirmed knee osteoarthritis. The walking‐related outcomes were obtained using equipment both from the research laboratory and the clinical setting. We used logistic regression to generate predictive models to determine candidate variables associated with a reduction in the knee adduction moment during walking – a surrogate for tibiofemoral load distribution, and a known biomechanical risk factor for osteoarthritis progression – with the use of standalone and arch‐supported lateral wedge insoles. Three different response thresholds (2%, 6%, and 10% reductions in the knee adduction moment) were used. Results In general, biomechanical responders were those who walked faster, were female, had less varus alignment, and had less severe radiographic severity. Findings were similar between the standalone and arch‐supported lateral wedge insoles, as well as between models using the laboratory‐derived or clinically‐available measures of walking performance. Conclusions Our hypothesis‐generating study provides valuable information that will inform future research into the efficient and effective use of lateral wedge insoles in the conservative management of knee osteoarthritis.

Soft X-ray spectromicroscopy at the O K-edge, U N4,5-edges and Ce M4,5-edges has been performed on focused ion beam sections of spent nuclear fuel for the first time, yielding chemical information on the sub-micrometer scale. To analyze these data, a modification to non-negative matrix factorization (NMF) was developed, in which the data are no longer required to be non-negative, but the non-negativity of the spectral components and fit coefficients is largely preserved. The modified NMF method was utilized at the O K-edge to distinguish between two components, one present in the bulk of the sample similar to UO2 and one present at the interface of the sample which is a hyperstoichiometric UO2+x species. The species maps are consistent with a model of a thin layer of UO2+x over the entire sample, which is likely explained by oxidation after focused ion beam (FIB) sectioning. In addition to the uranium oxide bulk of the sample, Ce measurements were also performed to investigate the oxidation state of that fission product, which is the subject of considerable interest. Analysis of the Ce spectra shows that Ce is in a predominantly trivalent state, with a possible contribution from tetravalent Ce. Atom probe analysis was performed to provide confirmation of the presence and localization of Ce in the spent fuel.

This cross-cultural ethnography explored the global student mobility patterns of international students from English-speaking countries in China and asked research questions about (a) their motivational factors and acculturation expectations before arrival; (b) linguistic factors influencing their acculturative stressors in the host group community's culture and its academic, social, and public systems after arrival; and (c) their reflections on intergroup ideologies with the host community after graduation, based on looking ahead. This study collected data through fieldwork by observing and interacting with approximately 80 individuals from the United Kingdom, the United States, Canada, Australia, and New Zealand in university towns in East China during the academic years from 2012 to 2023. In turn, 17 individuals who graduated before 2021 were selected as the final sample to conduct in-depth interviews. The study placed the concepts of acculturation expectations and intergroup ideologies at the nexus of linguistic hegemony, symbolic power, and social space. The overarching findings showed that despite positive motivations to visit China, language barriers led participants to express confusion, culture shock, anxiety, and perceived discrimination in their academic, social, and public domains. However, some participants who remained in China after graduation expressed their authentic voices regarding changes in attitude toward the host community culture and their heritage language. Therefore, this study focused on a different dimension of acculturation and linguistic ideology by examining how a linguistically and culturally dominant cohort faced acculturative challenges and negotiated to cope with their stressors in power dynamics. [ABSTRACT FROM AUTHOR]

Summary: Plasmid DNA (pDNA) transfection is advantageous for gene therapies requiring larger genetic elements, including “all-in-one” CRISPR/Cas9 plasmids, but is limited by toxicity as well as poor intracellular release and transfection efficiency in immune cell populations. Here, we developed a synthetic non-viral gene delivery platform composed of poly(ethylene glycol)-b-poly(propylene sulfide) copolymers linked to a cationic dendritic peptide (DP) via a reduceable bond, PEG-b-PPS-ss-DP (PPDP). A library of self-assembling PPDP polymers was synthesized and screened to identify optimal constructs capable of transfecting macrophages with small (pCMV-DsRed, 4.6 kb) and large (pL-CRISPR.EFS.tRFP, 11.7 kb) plasmids. The optimized PPDP construct transfected macrophages, fibroblasts, dendritic cells, and T cells more efficiently and with less toxicity than a commercial Lipo2K reagent, regardless of pDNA size and under standard culture conditions in the presence of serum. The PPDP technology described herein is a stimuli-responsive polymeric nanovector that can be leveraged to meet diverse challenges in gene delivery.

Current aptamer discovery approaches are unable to probe the complete space of possible sequences. Here, the authors use machine learning to facilitate the development of DNA aptamers with improved binding affinities, and truncate them without significantly compromising binding affinity.

In the early days of the coronavirus outbreak, we observed mask use in public among 1,330 people across China. People in regions with a history of farming rice wore masks more often than people in wheat regions. Cultural differences persisted after taking into account objective risk factors such as local COVID cases. The differences fit with the emerging theory that rice farming's labor and irrigation demands made societies more interdependent, with tighter social norms. Cultural differences were strongest in the ambiguous, early days of the pandemic, then shrank as masks became nearly universal (94%). Separate survey and internet search data replicated this pattern. Although strong cultural differences lasted only a few days, research suggests that acting just a few days earlier can reduce deaths substantially.

Introducing Chronos...

Natural biomolecules such as peptides and DNA can dynamically self-organize into diverse hierarchical structures. Here the authors report experiments and simulations on the dynamic network self-assembly and subsequent collapse of the synthetic homopolymer poly(propylene sulfone).

The current study examines whether the prevalence of COVID‐19 cases and cultural flexibility correlate to one's use of acceptance coping across 26 cultures. We analyzed data from 7476 participants worldwide at the start of the first outbreak from March 2020 to June 2020. Results showed that cultural flexibility moderated the relationship between COVID‐19 cases and individuals' acceptance coping strategies. Specifically, for cultures with high flexibility, COVID‐19 cases correlated with more acceptance coping; for cultures with low flexibility, COVID‐19 cases correlated with less acceptance coping. This result demonstrates how participants from flexible cultures can coexist with the realistic challenges and suffering faced during this pandemic. [ABSTRACT FROM AUTHOR]