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Abstract Many cellular processes are governed by protein–protein interactions that require tight spatial and temporal regulation. Accordingly, it is necessary to understand the dynamics of these interactions to fully comprehend and elucidate cellular processes and pathological disease states. To map de novo protein–protein interactions with time resolution at an organelle-wide scale, we developed a quantitative mass spectrometry method, time-resolved interactome profiling (TRIP). We apply TRIP to elucidate aberrant protein interaction dynamics that lead to the protein misfolding disease congenital hypothyroidism. We deconvolute altered temporal interactions of the thyroid hormone precursor thyroglobulin with pathways implicated in hypothyroidism pathophysiology, such as Hsp70-/90-assisted folding, disulfide/redox processing, and N-glycosylation. Functional siRNA screening identified VCP and TEX264 as key protein degradation components whose inhibition selectively rescues mutant prohormone secretion. Ultimately, our results provide novel insight into the temporal coordination of protein homeostasis, and our TRIP method should find broad applications in investigating protein-folding diseases and cellular processes.

Abstract Following peripheral nerve injury, successful axonal growth and functional recovery require Schwann cell (SC) reprogramming into a reparative phenotype, a process dependent upon c‐Jun transcription factor activation. Unfortunately, axonal regeneration is greatly impaired in aged organisms and following chronic denervation, which can lead to poor clinical outcomes. While diminished c‐Jun expression in SCs has been associated with regenerative failure, it is unclear whether the inability to maintain a repair state is associated with the transition into an axonal growth inhibition phenotype. We here find that reparative SCs transition into a senescent phenotype, characterized by diminished c‐Jun expression and secretion of inhibitory factors for axonal regeneration in aging and chronic denervation. In both conditions, the elimination of senescent SCs by systemic senolytic drug treatment or genetic targeting improved nerve regeneration and functional recovery, increased c‐Jun expression and decreased nerve inflammation. This work provides the first characterization of senescent SCs and their influence on axonal regeneration in aging and chronic denervation, opening new avenues for enhancing regeneration and functional recovery after peripheral nerve injuries.

Purpose: This systematic review and meta-analysis compared clinical outcome measures in patients undergoing reverse shoulder arthroplasty (RSA) for proximal humerus fracture (PHF) with healed versus non-healed greater tuberosity (GT). Methods: We performed a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines querying PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane for studies that stratified results by the GT healing status. Studies that did not attempt to repair the GT were excluded. We extracted and compared clinical outcomes including postoperative forward flexion (FF), external rotation (ER), internal rotation (IR), Constant score, and complications and revision rates. Results: Of the included patients, 295 (78.5%) demonstrated GT healing while 81 did not (21.5%). The healed GT cohort exhibited increased postoperative FF (P <.001), ER (P <.001), IR (P =.006), and Constant score (P =.006) compared to the non-healed GT cohort. The overall dislocation rate was 0.8% with no study differentiating GT status of dislocation cases. Conclusion: Healing of the GT after RSA for PHF yields improved postoperative range of motion and strength, whereas patient-reported pain and function were largely not affected by GT healing indicating merit to RSA for PHF regardless of the likelihood of the GT healing. [ABSTRACT FROM AUTHOR]

Black women living with HIV (BWLWH) face adversities associated with lower HIV medication adherence, viral non-suppression, and mental health symptoms (e.g., post-traumatic stress disorder) such as trauma/violence, racism, HIV-related discrimination/stigma, and gender-related stressors. We developed the first intervention based in cognitive behavioral therapy and culturally congruent coping for BWLWH to increase medication adherence and decrease PTSD symptoms by enhancing resilience, self-care, engagement in care, and coping for trauma, racism, HIV-related discrimination/stigma, and gender-related stressors. A pilot randomized control trial was conducted with BWLWH and histories of trauma who were at risk for their HIV viral load remaining or becoming detectable (i.e., below 80% medication adherence, detectable viral load in the past year, and/or missed HIV-related appointments). 119 BWLWH were assessed at baseline and 70 met inclusion criteria, completed one session of Life-Steps adherence counseling, and were randomized to either nine sessions of STEP-AD (Striving Towards EmPowerment and Medication Adherence) or ETAU (enhanced treatment as usual consisting of biweekly check-ins). Women completed a post intervention follow up assessment (3 months post baseline) and 3-month post intervention follow-up (6 months post baseline). Via STATA the difference-in-difference methodology with mixed models compared STEP-AD to ETAU on changes in outcomes over time. BWLWH in STEP-AD compared to E-TAU had significantly higher ART adherence (estimate = 9.36 p = 0.045) and lower likelihood of being clinically diagnosed with PTSD (OR =.07, estimate = − 2.66, p = 0.03) as well as borderline significance on higher CD4 count (estimate = 161.26, p = 0.05). Our findings suggest preliminary efficacy of STEP-AD in improving ART adherence, mental health, and immune function. [ABSTRACT FROM AUTHOR]

Background: This systematic review and meta-analysis sought to compare the clinical outcomes after proximal humerus reconstruction with a reverse allograft-prosthetic composite (APC) versus reverse endoprosthesis. Methods: Per PRISMA guidelines, we queried PubMed/MEDLINE, Embase, Web of Science, and Cochrane databases to identify articles reporting clinical outcomes of reverse APC or reverse endoprosthesis reconstruction of the proximal humerus for massive bone loss secondary to tumor, fracture, or failed arthroplasty. We compared postoperative range of motion, outcome scores, and the incidence of complications and revision surgery. Results: Of 259 unique articles, 18 articles were included (267 APC, 260 endoprosthesis). There were no significant differences between the APC and endoprosthesis cohort for postoperative forward elevation (P =.231), external rotation (P =.634), ASES score (P =.420), Constant score (P =.414), MSTS (P =.815), SST (P =.367), or VAS (P =.714). Rate of complications was 15% (31/213) in the APC cohort and 19% (27/144) in the endoprosthesis cohort. The rate of revision surgery was 12% after APC cohort and 7% after endoprosthesis. APC-specific complications included a 10% APC nonunion/malunion/resorption rate and 6% APC fracture/fragmentation rate. Discussion: Reverse APC and endoprosthesis are reasonable options for proximal humerus reconstruction. APC carries additional risks for complications, warranting evaluation of patients' healing capacity and surgeon experience. Level of Evidence: Level IV; Systematic Review. [ABSTRACT FROM AUTHOR]

Abstract Vaccination remains one of the most effective ways to limit the spread of infectious diseases, and reduce mortality and morbidity in rural areas. Waning public confidence in vaccines, especially the COVID-19 vaccine, remains a cause for concern. A number of individuals in the US and worldwide remain complacent, choosing not to be vaccinated and/or delay COVID-19 vaccination, resulting in suboptimal herd immunity. The primary goal of this study is to identify modifiable factors contributing to COVID-19 vaccine hesitancy among vaccine-eligible individuals with access to vaccines in two under-resourced rural states, Alaska and Idaho. This qualitative study used semi-structured interviews with providers and focus groups with community participants in Alaska and Idaho. A moderator’s guide was used to facilitate interviews and focus groups conducted and recorded using Zoom and transcribed verbatim. Thematic, qualitative analysis was conducted using QDA Miner. Themes and subthemes that emerged were labeled, categorized, and compared to previously described determinants of general vaccine hesitancy: established contextual, individual and/or social influences, vaccine and vaccination-specific concerns. Themes (n = 9) and sub-themes (n = 51) identified during the qualitative analysis highlighted a factor’s contributing to COVID-19 vaccine hesitancy and poor vaccine uptake. Relevant influenceable factors were grouped into three main categories: confidence, complacency, and convenience. Vaccines are effective public health interventions to promote health and prevent diseases in rural areas. Practical solutions to engage healthcare providers, researchers, vaccine advocates, vaccine manufacturers, and other partners in local communities are needed to increase public trust in immunization systems to achieve community immunity.

Background: The opioid overdose epidemic disproportionately impacts people experiencing homelessness. Outpatient-based opioid treatment (OBOT) programs have been established in homeless health care settings across the USA, but little is known about the success of these programs in engaging and retaining this highly marginalized patient population in addiction care. Objective: To evaluate predictors of initial engagement and subsequent attendance in a homeless-tailored OBOT program. Design: Prospective cohort study with 4 months of follow-up. Participants: A total of 148 homeless-experienced adults (≥18 years) who newly enrolled in the Boston Healthcare for the Homeless Program (BHCHP) OBOT program over a 1-year period (1/6/2022–1/5/2023). Main Measures: The primary outcomes were (1) initial OBOT program engagement, defined as having ≥2 additional OBOT visits within 1 month of OBOT enrollment, and (2) subsequent OBOT program attendance, measured monthly from months 2 to 4 of follow-up. Key Results: The average age was 41.7 years (SD 10.2); 23.6% were female, 35.8% were Hispanic, 12.8% were non-Hispanic Black, and 43.9% were non-Hispanic White. Over one-half (57.4%) were initially engaged. OBOT program attendances during months 2, 3, and 4 were 60.8%, 50.0%, and 41.2%, respectively. One-quarter (24.3%) were initially engaged and then attended the OBOT program every month during the follow-up period. Participants in housing or residential treatment programs (vs. unhoused; adjusted odds ratios (aORs) = 2.52; 95% CI = 1.17–5.44) and those who were already on or initiated a medication for opioid use disorder (OUD) (aOR = 6.53; 95% CI = 1.62–26.25) at the time of OBOT enrollment had higher odds of engagement. Older age (aOR = 1.74 per 10-year increment; 95% CI = 1.28–2.38) and initial engagement (aOR = 3.50; 95% CI = 1.86–6.59) conferred higher odds of attendance. Conclusions: In this study, over half initially engaged with the OBOT program, with initial engagement emerging as a strong predictor of subsequent OBOT program attendance. Interventions aimed at enhancing initial OBOT program engagement, including those focused on housing and buprenorphine initiation, may improve longer-term outcomes in this marginalized population. [ABSTRACT FROM AUTHOR]

Scientific practices describe behaviors scientists engage in while investigating the natural world. Educators should be aware of different science practice frameworks to better understand their students' progression for learning science practices across the K-20 spectrum. For example, a high school AP instructor would benefit from understanding both the K-12 frameworks their students have already experienced and the future undergraduate frameworks their students are moving toward. We were interested in exploring educator familiarity with the scientific practices outlined in the Next Generation Science and Engineering Practices, the Advanced Placement Science Practices, and Vision & Change Core Competencies. In practice, all science educators are teaching the same set of core principles around which these different frameworks are built. Under this view, it is a missed opportunity to not consider or draw on different frameworks to expand one's teaching practice. Using a cognitive constructionist approach, we describe the implementation of the "Science Practice Frameworks Concept Map Activity," designed to (1) introduce educators to scientific practices contained within Science Practice Frameworks and (2) show educators that despite these science practices targeting different student populations they are, at their core, very similar and often overlap. We present data showing a positive shift in educator familiarity with Science Practice Frameworks and present examples of participant concept maps that help us begin to understand how educators perceive the frameworks and the relationships between them, ensuring that educators are better prepared to guide students through a comprehensive understanding of science practices. [ABSTRACT FROM AUTHOR]

Primary care clinicians play a key role in asthma and asthma exacerbation management worldwide because most patients with asthma are treated in primary care settings. The high burden of asthma exacerbations persists and important practice gaps remain, despite continual advances in asthma care. Lack of primary care-specific guidance, uncontrolled asthma, incomplete assessment of exacerbation and asthma control history, and reliance on systemic corticosteroids or short-acting beta2-agonist-only therapy are challenges clinicians face today with asthma care. Evidence supports the use of inhaled corticosteroids (ICS) + fast-acting bronchodilator treatments when used as needed in response to symptoms to improve asthma control and reduce rates of exacerbations, and the symptoms that occur leading up to an asthma exacerbation provide a window of opportunity to intervene with ICS. Incorporating patient perspectives and preferences when designing asthma regimens will help patients be more engaged in their therapy and may contribute to improved adherence and outcomes. This expert consensus contains 10 Best Practice Advice Points from a panel of primary care clinicians and a patient representative, formed in collaboration with the International Primary Care Respiratory Group (IPCRG), a clinically led charitable organization that works locally and globally in primary care to improve respiratory health. The panel met virtually and developed a series of best practice statements, which were drafted and subsequently voted on to obtain consensus. Primary care clinicians globally are encouraged to review and adapt these best practice advice points on preventing and managing asthma exacerbations to their local practice patterns to enhance asthma care within their practice. [ABSTRACT FROM AUTHOR]

Sets of electrophilic probes are generally prepared using a narrow toolkit of robust reactions, which tends to limit both their structural and functional diversity. A unified synthesis of skeletally-diverse sulfonyl fluorides was developed that relied upon photoredox-catalysed dehydrogenative couplings between hetaryl sulfonyl fluorides and hydrogen donor building blocks. A set of 32 diverse probes was prepared, and then screened against Trypanosoma brucei. Four of the probes were found to have sub-micromolar anti-trypanosomal activity. A chemical proteomic approach, harnessing an alkynylated analogue and broad-spectrum fluorophosphonate tools, provided insights into the observed anti-trypanosomal activity, which likely stems from covalent modification of multiple protein targets. It is envisaged that the unified diversity-oriented approach may enable the discovery of electrophilic probes that have value in the elucidation of biological and biomedical mechanisms. Electrophilic bioactive compounds are useful chemical tools for identifying and modulating protein targets through reaction with nucleophilic amino acid side chain residues. Here, the authors report a modular synthesis of electrophilic sulfonyl fluoride probes, and evaluate their anti-trypanosomal activity using a chemoproteomics approach [ABSTRACT FROM AUTHOR]

The island of Sri Lanka was part of the South Asian mainland for the majority of the past 115,000 years, and connected most recently during the Last Glacial Maximum via the now submerged Palk Strait. The degree to which rising sea levels shaped past human adaptations from the Pleistocene and into the mid to late Holocene in Sri Lanka has remained unclear, in part because the earliest reliable records of human occupation come from the island's interior, where cave sites have revealed occupation of tropical forest ecosystems extending back to 48 thousand years (ka). The island's earliest known open-air sites are all much younger in date, with ages beginning at 15 ka and extending across the Holocene. Here we report the earliest well-dated open-air coastal site in Sri Lanka, Pathirajawela, which records human occupation back to ca. 25,000 years ago. We show that humans at Pathirajawela consistently adapted to changing ecosystems linked to sea level transgression and coastal evolution from the Last Glacial Maximum into the Holocene. The presence of anthropogenic shell midden deposits at the site from ca. 4.8 ka, focused almost exclusively on a single taxon, indicates intensification of estuarine resource exploitation, as humans responded to opportunities presented by the formation of new coastal ecosystems. [ABSTRACT FROM AUTHOR]

Certified peer support specialists (CPSS) are used as a paraprofessional workforce to engage hard-to-reach populations, including people experiencing homelessness. Thematic analysis was used to explore with CPSS (N = 7) what contributed to their effectiveness when working with this population. Participants were recruited at a HUD lead organization in the southeastern United States. Open-ended semi-structured questions were used in online, synchronous interviews. Themes related to three areas, experience, competence, and the organization, contributed to participants being effective. Specifically, interviewees observed that their lived experiences and abilities to speak a common language with clients contributed to their effectiveness. They identified how personal qualities and unique skillsets suited them for the work. Participants also valued the training they received; certification helped them to develop competencies and to balance vulnerability, empathy, and connection. Finally, participants attributed their effectiveness to clarity about their roles within the organization, supervision, attention to self-care, and co-worker support. Findings from this study may have implications for the value of lived and learned knowledge coexisting in organizations serving those who experience homelessness. [ABSTRACT FROM AUTHOR]

While explicit conceptual models help to inform research, they are left out of much of the health professions education (HPE) literature. One reason may be the limited understanding about how to develop conceptual models with intention and rigor. Group concept mapping (GCM) is a mixed methods conceptualization approach that has been used to develop frameworks for planning and evaluation, but GCM has not been common in HPE. The purpose of this article is to describe GCM in order to make it more accessible for HPE scholars. We recount the origins and evolution of GCM and summarize its core features: GCM can combine multiple stakeholder perspectives in a systematic and inclusive manner to generate explicit conceptual models. Based on the literature and prior experience using GCM, we detail seven steps in GCM: (1) brainstorming ideas to a specific "focus prompt," (2) preparing ideas by removing duplicates and editing for consistency, (3) sorting ideas according to conceptual similarity, (4) generating the point map through quantitative analysis, (5) interpreting cluster map options, (6) summarizing the final concept map, and (7) reporting and using the map. We provide illustrative examples from HPE studies and compare GCM to other conceptualization methods. GCM has great potential to add to the myriad of methodologies open to HPE researchers. Its alignment with principles of diversity and inclusivity, as well as the need to be systematic in applying theoretical and conceptual frameworks to practice, make it a method well suited for the complexities of contemporary HPE scholarship. [ABSTRACT FROM AUTHOR]

The article offers information on the need for updated health-related quality of life (HRQoL) data to improve newborn screening policy in the genomic era. Topics discussed include the significance of HRQoL in evaluating screening outcomes; challenges in measuring HRQoL for rare genetic conditions; and recommendations for collaborative efforts to advance patient-centered data collection.

Transect surveys are widely used to quantify mismanaged plastic waste discarded to the environment. However, very few studies have quantified inter-observer reliability in environmental waste surveys. The aim of this study was to assess inter-observer reliability for a set of environmental waste indicators derived from transect surveys in slum areas of two sub-Saharan African cities. Pairs of observers independently recorded counts of scattered waste items, large waste piles, and burnt waste along 64 environmental transects in Kisumu, Kenya, and Greater Accra, Ghana. Concordance correlation coefficients were used to measure inter-observer reliability for derived indicators measuring mismanaged waste density, waste composition, waste origins of policy concern, and waste disposal practices. Evidence across all observers consistently showed that single-use disposable diapers, discarded Personal Protective Equipment, and bagged or bottled water are locally important constituents of mismanaged waste in both cities that should be addressed through urban waste management strategies. In both cities, there was generally excellent inter-observer reliability for density of burnt waste and density of large waste piles (concordance correlation coefficient > 0.9 for all but one observer pair), but weak to moderate inter-observer reliability for scattered waste density and densities of specific waste items such as disposable nappies and discarded Personal Protective Equipment. Our study shows that beach litter survey protocols can be adapted for use in slums. However, to generate robust estimates of scattered waste, its composition, and waste origins of policy concern in slums, assessment of inter-observer reliability should be incorporated into field team training. [ABSTRACT FROM AUTHOR]

The nucleus accumbens (NAc) regulates reward-motivated behavior, but the temporal dynamics of NAc neurons that enable "free-willed" animals to obtain rewards remain elusive. Here, we recorded Ca2+ activity from individual NAc neurons when mice performed self-paced lever-presses for sucrose. NAc neurons exhibited three temporally-sequenced clusters, defined by times at which they exhibited increased Ca2+ activity: approximately 0, −2.5 or −5 sec relative to the lever-pressing. Dopamine D1 receptor (D1)-expressing neurons and D2-neurons formed the majority of the −5-sec versus −2.5-sec clusters, respectively, while both neuronal subtypes were represented in the 0-sec cluster. We found that pre-press activity patterns of D1- or D2-neurons could predict subsequent lever-presses. Inhibiting D1-neurons at −5 sec or D2-neurons at −2.5 sec, but not at other timepoints, reduced sucrose-motivated lever-pressing. We propose that the time-specific activity of D1- and D2-neurons mediate key temporal features of the NAc through which reward motivation initiates reward-seeking behavior. Volitional reward taking emerges through a sequence of preluding events. Yet, the underlying neural mechanism is not fully understood. Here authors show a series of temporal dynamics of nucleus accumbens neurons that may substantiate such preluding events to commit "free-willed" animals to reward taking. [ABSTRACT FROM AUTHOR]

Squamous odontogenic tumor (SOT) is an exceedingly rare, benign epithelial odontogenic tumor showing squamous differentiation. It is composed of variably sized and shaped islands of cytologically bland, mature squamous epithelium within a fibrous stroma. In this report, we present a rare transformation of a squamous odontogenic tumor (SOT) of the maxilla into a well-differentiated squamous cell carcinoma (SCC) with involvement of the pterygoid plates. To the best of our knowledge, only two cases of malignant transformation of SOT has been reported in the literature. Herein, we seek to report this extremely rare occurrence to raise awareness of oral and maxillofacial surgeons and pathologists of this unusual, but serious event and perform a literature review of squamous odontogenic tumors. [ABSTRACT FROM AUTHOR]

Caloric restriction extends healthy lifespan in multiple species1. Intermittent fasting, an alternative form of dietary restriction, is potentially more sustainable in humans, but its effectiveness remains largely unexplored2–8. Identifying the most efficacious forms of dietary restriction is key for developing interventions to improve human health and longevity9. Here we performed an extensive assessment of graded levels of caloric restriction (20% and 40%) and intermittent fasting (1 and 2 days fasting per week) on the health and survival of 960 genetically diverse female mice. We show that caloric restriction and intermittent fasting both resulted in lifespan extension in proportion to the degree of restriction. Lifespan was heritable and genetics had a larger influence on lifespan than dietary restriction. The strongest trait associations with lifespan included retention of body weight through periods of handling—an indicator of stress resilience, high lymphocyte proportion, low red blood cell distribution width and high adiposity in late life. Health effects differed between interventions and exhibited inconsistent relationships with lifespan extension. 40% caloric restriction had the strongest lifespan extension effect but led to a loss of lean mass and changes in the immune repertoire that could confer susceptibility to infections. Intermittent fasting did not extend the lifespan of mice with high pre-intervention body weight, and two-day intermittent fasting was associated with disruption of erythroid cell populations. Metabolic responses to dietary restriction, including reduced adiposity and lower fasting glucose, were not associated with increased lifespan, suggesting that dietary restriction does more than just counteract the negative effects of obesity. Our findings indicate that improving health and extending lifespan are not synonymous and raise questions about which end points are the most relevant for evaluating aging interventions in preclinical models and clinical trials.Health effects of dietary restriction are uncoupled from longevity. [ABSTRACT FROM AUTHOR]

Sets of electrophilic probes are generally prepared using a narrow toolkit of robust reactions, which tends to limit both their structural and functional diversity. A unified synthesis of skeletally-diverse sulfonyl fluorides was developed that relied upon photoredox-catalysed dehydrogenative couplings between hetaryl sulfonyl fluorides and hydrogen donor building blocks. A set of 32 diverse probes was prepared, and then screened against Trypanosoma brucei. Four of the probes were found to have sub-micromolar anti-trypanosomal activity. A chemical proteomic approach, harnessing an alkynylated analogue and broad-spectrum fluorophosphonate tools, provided insights into the observed anti-trypanosomal activity, which likely stems from covalent modification of multiple protein targets. It is envisaged that the unified diversity-oriented approach may enable the discovery of electrophilic probes that have value in the elucidation of biological and biomedical mechanisms. Electrophilic bioactive compounds are useful chemical tools for identifying and modulating protein targets through reaction with nucleophilic amino acid side chain residues. Here, the authors report a modular synthesis of electrophilic sulfonyl fluoride probes, and evaluate their anti-trypanosomal activity using a chemoproteomics approach [ABSTRACT FROM AUTHOR]

In many non-human species, learning retention decreases temporarily following training. This has led to the suggestion that these lapses reflect a fundamental component of memory formation. If so, transient memory lapses should also be prevalent in humans, and should occur for all types of learning. In line with these predictions, we report two cases of transient memory lapses in humans that occur 1–3 h after training on a perceptual-discrimination task. The results indicate that the occurrence of transient memory lapses extends to perceptual learning, a form of skill learning, and suggest that transient memory lapses may be a common but overlooked facet of memory formation in humans. [ABSTRACT FROM AUTHOR]

Adiposity is an established risk factor for multiple diseases, but the causal relationships of different adiposity types with circulating protein biomarkers have not been systematically investigated. We examine the causal associations of general and central adiposity with 2923 plasma proteins among 3977 Chinese adults (mean BMI = 23.9 kg/m²). Genetically-predicted body mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-to-hip ratio (WHR) are significantly (FDR < 0.05) associated with 399, 239, 436, and 283 proteins, respectively, with 80 proteins associated with all four and 275 with only one adiposity trait. WHR is associated with the most proteins (n = 90) after adjusting for other adiposity traits. These associations are largely replicated in Europeans (mean BMI = 27.4 kg/m²). Two-sample Mendelian randomisation (MR) analyses in East Asians using cis-protein quantitative trait locus (cis-pQTLs) identified in GWAS find 30/2 proteins significantly affect levels of BMI/WC, respectively, with 10 showing evidence of colocalisation, and seven (inter-alpha-trypsin inhibitor heavy chain H3, complement factor B, EGF-containing fibulin-like extracellular matrix protein 1, thioredoxin domain-containing protein 15, alpha-2-antiplasmin, fibronectin, mimecan) are replicated in separate MR using different cis-pQTLs identified in Europeans. These findings identified potential novel mechanisms and targets, to our knowledge, for improved treatment and prevention of obesity and associated diseases. A study in lean Chinese adults shows that general and central adiposity affects plasma levels of <650 proteins. Moreover, 31 proteins are found to influence levels of adiposity, providing potential targets for developing treatment for obesity. [ABSTRACT FROM AUTHOR]

Recruitment of the catadromous and critically endangered European eel Anguilla anguilla in Europe has declined substantially since the 1980s, with considerable knowledge gaps remaining in many aspects of their life cycle. The aim was to assess eel migration phenology in three regulated rivers in England between 2009 and 2019 through analyses of eel numbers using passes at their tidal limits, with calculation of the annual timings of migration initiation (10% of all eels passed, T10), peak (50%, T50) and conclusion (90%, T90). Across the three rivers, T10 varied between Julian Day ('Day') 94 and 173. Years of earlier T10 had significantly earlier T50, where T50 varied between Day 105 and 200. The considerable inter-annual variability in migration timings was associated with environmental variables; earlier T10 and T50 occurred in years of warmer river temperatures (RTs) and cooler sea surface temperatures (SST), and in years where RTs were higher than SSTs. No environmental variables were significant predictors of T90. These results indicate that whilst there is annual variability in the timing of eel migration initiation and peak into freshwaters, this variability is predictable according to differences in environmental conditions. As many of these conditions associated with annual variability in temperature and precipitation then climate change has the potential to shift these migration timings. [ABSTRACT FROM AUTHOR]

Background: For women at increased risk of breast cancer, the National Comprehensive Cancer Network (NCCN) guidelines recommend clinical encounters every 6–12 months. While screening mammography has corresponded with a relative risk reduction in breast cancer mortality of approximately 20%, evidence validating clinical breast examination (CBE) as an efficacious screening modality is deficient. Our study aimed to assess the conventional merit of regular CBE for breast cancer detection among individuals at increased risk of breast cancer development. Methods: Women > 18 years with documented high-risk encounters at Corewell Health West from 1 January 2018 to 31 December 22 were retrospectively reviewed. High-risk criteria included genetic predisposition, 5-year (> 1.7%) or lifetime (> 20%) Tyrer–Cuzick and/or Gail Model risk estimations, thoracic radiotherapy before age 30 years, lobular carcinoma in-situ, or atypical hyperplasia. Patients with a history of breast cancer or bilateral prophylactic mastectomy prior to 2018 were excluded. Results: Of the 9171 cumulative high-risk encounters among 2493 women, only one breast cancer was detected by CBE. CBE resulted in 1 (0.04%) cancer diagnosis compared with 30 (1.2%) detected on screening imaging and 10 (0.4%) self-reported. Of the 30 image-detected cancers, 28 (93.3%) had no detectable clinical findings at the time of preoperative consultation. Self-reported and CBE-detected cancers were more likely to be of higher clinical stage compared with imaging-detected malignancies. Conclusions: The role of routine CBE as a cancer detection modality in the high-risk patient population appears to be limited. Telemedicine can be offered to individuals who have completed screening imaging but are unable to commit and/or are inconvenienced by in-person high-risk breast cancer assessments. [ABSTRACT FROM AUTHOR]

Introduction: Racial disparities in disease activity, clinical outcomes, and treatment survival persist despite advancements in rheumatoid arthritis (RA) therapies and clinical management. In this post hoc analysis of pooled data from the tofacitinib global clinical program, we evaluated the impact of race on the efficacy and safety of tofacitinib in patients with RA. Methods: Data were pooled from 15 phase 2–3b/4 studies of patients with RA treated with tofacitinib 5 or 10 mg twice daily, adalimumab, or placebo. Outcomes were stratified by self-reported patient race (White/Black/Asian/Other). Efficacy outcomes to month 12 included: American College of Rheumatology (ACR)20/50/70 responses, Clinical Disease Activity Index (CDAI)/Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] low disease activity (LDA) rates, least squares (LS) mean change from baseline (∆) in CDAI, DAS28-4 (ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), and Pain [Visual Analog Scale (VAS)]. Odds ratios (ORs; 95% CI) versus placebo, and placebo-adjusted ∆LS means were calculated for active treatments using logistic regression model and mixed-effect model of repeated measurements, respectively. Safety outcomes were assessed throughout. Results: A total of 6355 patients were included (White, 4145; Black, 213; Asian, 1348; Other, 649). For tofacitinib-treated patients, ORs for ACR20/50/70 responses and CDAI/DAS28-4(ESR) LDA rates through month 3 were generally numerically higher for White/Asian/Other versus Black patients. Across active treatments, trends toward higher placebo-adjusted improvements from baseline in CDAI, DAS28-4 (ESR), HAQ-DI, and Pain (VAS) were observed in Asian/Other versus White/Black patients. Numerically higher placebo responses in Black versus White/Asian/Other patients were generally observed across outcomes through month 12. Safety outcomes were mostly similar across treatment/racial groups. Conclusions: In patients with RA, tofacitinib was efficacious across racial groups with similar safety outcomes; observed racial differences potentially reflect patient demographics or regional practice disparities. Trial Registration Numbers: ClinicalTrials.gov identifiers: NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01359150; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055. [ABSTRACT FROM AUTHOR]

A growing body of research documents that the use of pornography is becoming more frequent among male sexual minorities. According to the sexual script acquisition, activation, application model of mediated sexual socialization (3AM), pornography can be considered a potential factor influencing an individual's partner preference. In addition, perceived realism could moderate the link between pornography consumption and partner preferences. This study explored the relationship between pornographic video consumption and partner preference among male sexual minorities and the moderating role of perceived realism. A total of 595 male sexual minorities aged 18 to 47 years (M = 21.70, SD = 3.83), including 82.9% gay men and 17.1% bisexual men, were enrolled in the study. Our results revealed the following: (1) The frequency of pornographic video consumption and male sexual minorities' preferences for appearance and sexual ability in partner selection were positively correlated (r =.06/.07, ps <.05). (2) When perceived realism was low, pornographic video consumption was not significantly associated with appearance and sexual ability preference. (3) Conversely, when perceived realism was high, pornographic video consumption was positively associated with appearance and sexual ability preference (β =.17/.16, ps <.01). Findings highlight the mechanisms behind pornographic video consumption and partner preference in sexual minority males. [ABSTRACT FROM AUTHOR]

Mass die-offs, reduced species richness and local extinctions of freshwater mussels have resulted from river drying events, which often co-occur with high ambient temperatures. These events are predicted to increase in frequency and severity under the influence of climate change. We aimed to identify the desiccation tolerance of two freshwater mussel species (the river mussel Alathyria jacksoni and the floodplain mussel Velesunio ambiguus) across a range of temperatures by simulating river drying events in laboratory conditions. Freshwater mussels were buried in sediment heated to 29, 32, 35, 38 and 41°C. Lethal times and lethal temperatures at which 50% mortality occurred were used to infer species-specific tolerances. The lethal time for 50% of mussels to reach mortality at 29°C was shorter for A. jacksoni (14 days) than V. ambiguus (58 days) but did not differ markedly at higher temperatures. Lethal temperatures were also similar between species over short durations (e.g. 39–40°C at 1 day). Our results suggest that the difference in desiccation tolerance between species diminishes toward their upper thermal limit. Management interventions aimed at reducing sediment temperatures, such as providing shade via riparian vegetation and wetting from environmental flows, could help alleviate the impact of drying events and climate change on both freshwater mussel species. [ABSTRACT FROM AUTHOR]

A simple formula is proven for the maximal amplitudes of N-phase hyperelliptic solutions of the modified nonlinear Schrödinger equation. The simple formula for the maximal amplitude depends only on the roots of an invariant polynomial. [ABSTRACT FROM AUTHOR]

Controlled delivery of proteins and other biologics is a growing medium of therapy for diseases previously untreatable. Here we report a self-assembling, tunable vesicle for the controlled delivery of growth factors and cytokines. Coacervate made of heparin and a biocompatible polycation, PEAD, forms the core of the vesicle; lipids form the membrane of the vesicle. We call this vesicle lipocoacervate (LipCo), which has a high affinity for growth factors and cytokines due to heparin. LipCo is a tunable protein delivery vehicle. The vesicle size is controlled through polymer and salt concentrations. Membrane functionalization enables potential for targeting capabilities with long-term storage through lyophilization. Importantly, the controlled delivery of therapeutics also avoids high toxicity to treated cells in vitro. Here we report on these key principles of LipCo assembly and design. [ABSTRACT FROM AUTHOR]

Maintaining hydrological connectivity is important for sustaining freshwater fish populations as the high habitat connectivity supports large-scale fish movements, enabling individuals to express their natural behaviours and spatial ecology. Northern pike Esox lucius is a freshwater apex predator that requires access to a wide range of functional habitats across its lifecycle, including spatially discrete foraging and spawning areas. Here, pike movement ecology was assessed using acoustic telemetry and stable isotope analysis in the River Bure wetland system, eastern England, comprising of the Bure mainstem, the River Ant and Thurne tributaries, plus laterally connected lentic habitats, and a system of dykes and ditches. Of 44 tagged pike, 30 were tracked for over 100 days, with the majority of detections being in the laterally connected lentic habitats and dykes and ditches, but with similar numbers of pike detected across all macrohabitats. The movement metrics of these pike indicated high individual variability, with total ranges to over 26 km, total movements to over 1182 km and mean daily movements to over 2.9 km. Pike in the Thurne tributary were more vagile than those in the Ant and Bure, and with larger Thurne pike also having relatively high proportions of large-bodied and highly vagile common bream Abramis brama in their diet, suggesting the pike movements were potentially related to bream movements. These results indicate the high individual variability in pike movements, which was facilitated here by their access to a wide range of connected macrohabitats due to high hydrological connectivity. [ABSTRACT FROM AUTHOR]

Aims: Evaluate the social determinants of health (SDOH) associated with suicidality among female Service Members and Veterans (SMV) in Arizona. Methods: Used data from a statewide Arizona Veteran Survey (n = 1,134) to analyze SDOH associated with suicidality (any self-report of suicidal ideation, suicide attempt, or calling a crisis line). Response data were cross-tabulated and analyzed for statistical significance using a chi-square test with a p-value of p < 0.05. Results: Depression, disability, barriers to treatment, housing instability, feelings of loneliness, and more were associated with increased suicidality among respondents. Substance use within the last 30 days, social support, and Veteran social support were not found to be significantly associated with suicidality. Conclusions: Female SMV populations experiencing social, economic, and health disparities appear to be at higher risk for suicide. These findings suggest that future suicide prevention efforts may be more effective if tailored towards populations in need of additional support and social services. [ABSTRACT FROM AUTHOR]

Context: Fire-adapted species have evolved to exploit resources in heterogenous landscapes that presumably maximize energy acquisition and minimize energetic expenditure. However, limited empirical work exists demonstrating the explicit energetic mechanisms that drive such adaptive responses to fire across diverse landscapes. Objectives: The California spotted owl (Strix occidentalis occidentalis) appears to benefit from landscape heterogeneity and preferentially uses smaller patches of severely burned forest, a behavior that has been hypothesized as adaptive. Here, we investigate empirical support for this hypothesis. Methods: We leveraged high-resolution GPS tracking and nest video monitoring to examine the hunting success, movement, and nest provisioning of 34 spotted owls in the Sierra Nevada and San Bernardino Mountains, California across burned and unburned landscapes. Results: Regardless of time since fire, individuals avoided foraging directly within moderately or severely burned patches. 1 to 2 years post-fire, individuals had more success capturing prey in unburned forest, and the energy individuals spent moving increased with the proportion of high-severity fire and decreased with the proportion unburned forest. Multiple years after a fire, individuals had more success capturing prey, spent less energy moving, and provisioned more energy to nests in landscapes with more low-severity fire. Conclusions: These results support the hypothesis that spotted owls are adapted to fire-prone landscapes and that disturbance events within this region’s natural range of variation can ultimately promote hunting and provisioning. As fires deviate from regional norms across the globe, the negative impacts of fire may become more extreme and long-term benefits of fire may degrade for animals in fire-prone landscapes. Examining the mechanistic impacts of disturbance can allow us to better understand animal responses to rapidly changing landscapes. [ABSTRACT FROM AUTHOR]

This article discusses a case of anti-Melanoma Differentiation-Associated Gene 5 (anti-MDA5) dermatomyositis, a rare form of immune-mediated dermatomyositis. The patient, a 73-year-old male, presented with muscle weakness and falls but did not exhibit the typical cutaneous findings or rapidly progressive lung disease associated with anti-MDA5 dermatomyositis. The article highlights the diverse phenotypic spectrum and prognosis of the disease, emphasizing the need for clinicians to consider the diagnosis even in the absence of classic symptoms. The patient's course was complicated by acute colonic pseudo-obstruction, a rare complication of autoimmune diseases. Despite the atypical presentation, the patient showed improvement with treatment and remained stable at follow-up. [Extracted from the article]

Purpose: Vitamin A is a lipid-soluble compound that is critical in maintaining phototransduction. Ocular manifestations of hypovitaminosis A may present with anterior segment signs of xeropthalmia, with advanced cases also causing classic retinal and electrophysiologic changes of vitamin A deficiency retinopathy. We present a case of vitamin A deficiency retinopathy, with corresponding retinal imaging and electrophysiology, in an adult patient with celiac disease and liver fibrosis. Methods: A single case report was conducted in Toronto, Canada. Results: A 77-year-old male with known celiac disease and liver fibrosis presented progressively worsening vision noticed primarily when driving. Vision was 20/50 OD and 20/200 OS. Bitot spots were noted on anterior segment examination. Fundus photography demonstrated bilateral peripheral macular hypopigmentation and far-peripheral granular retinal hypopigmentation with focal yellow dots and hyper-pigmented deposits. Optical coherence tomography (OCT) imaging demonstrated indistinct outer retinal banding with mild outer nuclear layer thinning, focal hyper-reflective deposits, and a thin choroid bilaterally. Full-field electroretinography (ERG) testing demonstrated reduced rod-isolated and combined rod-cone response amplitudes, and multifocal ERG testing demonstrated blunted individual responses throughout the field. The patient was treated with pulse vitamin A therapy. After 6 months of therapy, ERG responses were back within reference range, and the outer retinal changes reversed; visual acuity improved to 20/30 OD and 20/40 OS. Conclusion: This case represents the classic findings of vitamin A deficiency retinopathy on fundus examination and electrophysiologic testing secondary to gastrointestinal pathology. Prompt treatment of high dose vitamin A supplementation led to improvement of full-field and multifocal ERG results, as well as reconstitution of outer retinal architecture. [ABSTRACT FROM AUTHOR]

Introduction: In sarcoidosis granulomas, monocyte-derived macrophages are activated by pro-inflammatory cytokines including TNF and IL-6. Current drug treatment for sarcoidosis aims to suppress inflammation but disabling side effects can ensue. The macrolide azithromycin may be anti-inflammatory. We aimed to determine whether treatment with azithromycin affects blood inflammatory gene expression and monocyte functions in sarcoidosis. Methods: Blood samples were collected from patients with chronic pulmonary sarcoidosis enrolled in a single arm, open label clinical trial who received oral azithromycin 250 mg once daily for 3 months. Whole blood inflammatory gene expression with or without LPS stimulation was measured using a 770-mRNA panel. Phenotypic analysis and cytokine production were conducted by flow cytometry and ELISA after 24h stimulation with growth factors and TLR ligands. mTOR activity was assessed by measuring phosphorylated S6RP. Results: Differential gene expression analysis indicated a state of heightened myeloid cell activation in sarcoidosis. Compared with controls, sarcoidosis patients showed increased LPS responses for several cytokines and chemokines. Treatment with azithromycin had minimal effect on blood gene expression overall, but supervised clustering analysis identified several chemokine genes that were upregulated. At the protein level, azithromycin treatment increased LPS-stimulated TNF and unstimulated IL-8 production. No other cytokines showed significant changes following azithromycin. Blood neutrophil counts fell during azithromycin treatment whereas mononuclear cells remained stable. Azithromycin had no detectable effects on mTOR activity or activation markers. Conclusion: Blood myeloid cells are activated in sarcoidosis, but azithromycin therapy did not suppress inflammatory gene expression or cytokine production in blood. Trial registration: EudraCT 2019-000580-24 (17 May 2019) [ABSTRACT FROM AUTHOR]

Urban riparian vegetation is frequently dominated by invasive weeds, whose growth is often attributed to the elevated nitrogen and phosphorous in urban waters and soils. However, less recognition is given to other urban contaminants that may influence riparian vegetation. Previous studies have indicated that the dissolution of concrete modifies water and soil geochemistry and potentially enhances the growth of invasive species. This study investigated the relationship between urban water quality and the growth of an invasive urban riparian weed, willow (Salix spp.), to examine the contribution and influence of concrete materials. The study used water from endangered upland peat wetlands within and adjoining the Greater Blue Mountains World Heritage Area, many of which are in urban catchments and suffer degradation from water pollution and invasive weeds. In this study, willow cuttings were grown in a laboratory using four water treatments: pristine (non-urban), urban, and non-urban water exposed to two different concrete materials. The urban and concrete-exposed water treatments were associated with increased plant growth measures in addition to increased concentrations of barium and strontium that bioaccumulated in plant tissue. [ABSTRACT FROM AUTHOR]

Background: Ventricular tachycardia (VT) reduces cardiac output through high heart rates, loss of atrioventricular synchrony, and loss of ventricular synchrony. We studied the contribution of each mechanism and explored the potential therapeutic utility of His bundle pacing to improve cardiac output during VT. Methods: Study 1 aimed to improve the understanding of mechanisms of harm during VT (using pacing simulated VT). In 23 patients with left ventricular impairment, we recorded continuous ECG and beat-by-beat blood pressure measurements. We assessed the hemodynamic impact of heart rate and restoration of atrial and biventricular synchrony. Study 2 investigated novel pacing interventions during clinical VT by evaluating the hemodynamic effects of His bundle pacing at 5 bpm above the VT rate in 10 patients. Results: In Study 1, at progressively higher rates of simulated VT, systolic blood pressure declined: at rates of 125, 160, and 190 bpm, -22.2%, -42.0%, and -58.7%, respectively (ANOVA p < 0.0001). Restoring atrial synchrony alone had only a modest beneficial effect on systolic blood pressure (+ 3.6% at 160 bpm, p = 0.2117), restoring biventricular synchrony alone had a greater effect (+ 9.1% at 160 bpm, p = 0.242), and simultaneously restoring both significantly increased systolic blood pressure (+ 31.6% at 160 bpm, p = 0.0003). In Study 2, the mean rate of clinical VT was 143 ± 21 bpm. His bundle pacing increased systolic blood pressure by + 14.2% (p = 0.0023). In 6 of 10 patients, VT terminated with His bundle pacing. Conclusions: Restoring atrial and biventricular synchrony improved hemodynamic function in simulated and clinical VT. Conduction system pacing could improve VT tolerability and treatment. [ABSTRACT FROM AUTHOR]

Pornography consumption remains a common media behavior despite the ever-increasing proliferation of digital media options. A recent meta-analysis found evidence that higher rates of pornography consumption are associated with heightened perceptions of pornography's realism, but the potential downstream effects of perceiving pornography as realistic have yet to receive a meta-analytic treatment. The present paper describes our efforts to conduct such a meta-analysis. To our surprise, there was a dearth of literature available. And yet, the extant research base suggests that perceived pornography realism may be associated with a number of sociologically, relationally, and personally impactful sexual beliefs and behaviors. Discussion centers on how interested scholars can move this important line of sexuality and culture research forward in the years to come. [ABSTRACT FROM AUTHOR]

Deep phenotyping describes the use of standardised terminologies to create comprehensive phenotypic descriptions of biomedical phenomena. These characterisations facilitate secondary analysis, evidence synthesis, and practitioner awareness, thereby guiding patient care. The vast majority of this knowledge is derived from sources that describe an academic understanding of disease, including academic literature and experimental databases. Previous work indicates a gulf between the priorities, perspectives, and perceptions held by different healthcare stakeholders. Using social media data, we develop a phenotype model that represents a public perspective on disease and compare this with a model derived from a combination of existing academic phenotype databases. We identified 52,198 positive disease-phenotype associations from social media across 311 diseases. We further identified 24,618 novel phenotype associations not shared by the biomedical and literature-derived phenotype model across 304 diseases, of which we considered 14,531 significant. Manifestations of disease affecting quality of life, and concerning endocrine, digestive, and reproductive diseases were over-represented in the social media phenotype model. An expert clinical review found that social media-derived associations were considered similarly well-established to those derived from literature, and were seen significantly more in patient clinical encounters. The phenotype model recovered from social media presents a significantly different perspective than existing resources derived from biomedical databases and literature, providing a large number of associations novel to the latter dataset. We propose that the integration and interrogation of these public perspectives on the disease can inform clinical awareness, improve secondary analysis, and bridge understanding and priorities across healthcare stakeholders. [ABSTRACT FROM AUTHOR]

This paper describes an approach for developing strategic cycle network planning tools. Based on our experience developing and deploying the Cycle Route Uptake and Scenario Estimation (CRUSE) Tool for Ireland, we outline the underlying methods, including disaggregation of origin–destination data with the open source 'odjitter' software, incorporation of additional trip purposes, routing, scenario generation, and development of an intuitive user interface that is tested and used by practitioners. Commissioned by the national infrastructure agency Transport Infrastructure Ireland, CRUSE provides estimates of current and potential future cycling levels under 'snapshot' scenarios to inform investment decisions. The publicly available results at https://cruse.bike/ enable planners, engineers, and other stakeholders to make more evidence-based decisions. CRUSE goes beyond previous work by: modeling networks at high spatial resolution; simulating multiple trip purposes (social, shopping, personal utility, recreational, and cycle touring), supplementing official origin–destination datasets on travel for work and education; and providing estimates of 'quietness' (a proxy for cyclist comfort and route preference) at the route segment level. Three network types—'Fastest', 'Balanced', and 'Quietest'—help plan both arterial and residential cycle networks. Workshops with stakeholders were used to inform the development of the tool. Feedback shows that the tool has a wide range of uses and is already being used in practice to inform urban, inter-urban, and rural cycle network designs. The approach is flexible and open source, allowing the underlying ideas and code to be adapted, supporting more evidence-based and effective cycling policies and interventions internationally. [ABSTRACT FROM AUTHOR]

The ocean will ultimately store most of the CO2 emitted to the atmosphere by human activities. Despite its importance, estimates of the 2000−2022 trend in the ocean CO2 sink differ by a factor of two between observation-based products and process-based models. Here we address this discrepancy using a hybrid approach that preserves the consistency of known processes but constrains the outcome using observations. We show that the hybrid approach reproduces the stagnation of the ocean CO2 sink in the 1990s and its reinvigoration in the 2000s suggested by observation-based products and matches their amplitude. It suggests that process-based models underestimate the amplitude of the decadal variability in the ocean CO2 sink, but that observation-based products on average overestimate the decadal trend in the 2010s. The hybrid approach constrains the 2000−2022 trend in the ocean CO2 sink to 0.42 ± 0.06 Pg C yr−1 decade−1, and by inference the total land CO2 sink to 0.28 ± 0.13 Pg C yr−1 decade−1. A hybrid approach reconciles discrepancies between observation-based and ocean model estimates of the ocean CO2 sink. It shows that ocean models underestimate variability, while observation-based methods tend to overestimate the 2010s trend. [ABSTRACT FROM AUTHOR]

Background: Paddy soil is a typical soil type affected by anthropogenic management and factors related to natural soil formation. The evolution from mudflats to typical paddy soils can significantly affect the soil microecology. Previous studies have reported the evolution of soil physicochemical properties, microbes, and related soil environmental factors in a millennium paddy soil chronosequence. However, the potential biological mechanisms of changes in metabolites and microbes–metabolites interaction are poorly understood. Therefore, a combination of high-throughput sequencing and environmental pseudotargeted metabolomics techniques was adopted to explore the effects of the millennium paddy soil chronosequence on microbial communities, metabolites, and their functions and interactions. Results: The soil ecology changed greatly in the first 60 years of the transition from mudflat to paddy planting. Among the microbial communities, the response of the bacteria to the chronosequence was more sensitive than that of fungi. Among them, the bacterial communities of Proteobacteria, Bacteroidetes, Acidobacteria, and Nitrospirae exhibited regular succession over the chronosequence, but the fungal communities did not show regular changes. Bacterial function prediction revealed that the beginning of the critical stage of the evolution from mudflat to paddy soil involved the organic matter cycle and energy flow. In contrast, fungi were characterized mainly by pathogenic and saprophytic functions. The results of the principal component analysis of the metabolites revealed a similar pattern of change as that of the microbes. Seventy-five characteristic metabolites exhibited three trends of change during the development of the paddy soil chronosequence. Twenty-five differentially active metabolic pathways, including glyoxylate and dicarboxylate metabolism, starch and sucrose metabolism, and galactose metabolism, were enriched. In addition, correlation analysis revealed that long-chain fatty acids, short-chain fatty acids, phenolic acids, carbohydrates, and polyalcohols significantly regulate the microbial communities in paddy soil. Conclusions: Combining metabolome and microbiome has expanded the overall understanding of the development of paddy soil under anthropogenic management. During the development of a paddy soil chronosequence, the synergistic regulation of soil physicochemical properties and metabolites in the microbial community results in increased productivity. This study provides a new perspective on microbes and metabolites interaction. [ABSTRACT FROM AUTHOR]

Porous ionic electrospray emitters have received significant interest for space propulsion due to their performance and operational simplicity. We have developed a diffusion equation for describing the transient flow response in a porous electrospray emitter, which allows for the prediction of the settling time for flow in the porous emitter. This equation accounts for both the change in liquid storage at exposed pores on the emitter with pressure and viscous diffusion through Darcy's law. Transient flow solutions are provided for the most common emitter topologies: pillar, cone, and wedge. Transient flow solutions describe the settling time and magnitude of current overshoot from porous electrosprays, while providing useful guidelines for reducing transient response time through emitter design. Comparing diffusion of pressure to the onset delay model for electrospray emission shows that diffusion is most relevant at higher voltages and when a porous reservoir is used. Accounting for multiple emission sites on the wedge geometry shows that emission sites settle in proportion to emission site spacing to the power − 1.74. Article Highlights: The transient response of porous electrosprays is affected by fluid storage in exposed pores. Pressure diffuses into a porous electrospray through depletion of fluid in exposed pores. Diffusion of pressure complements the existing onset delay model for porous electrosprays. [ABSTRACT FROM AUTHOR]

While multiple factors impact disease, artificial intelligence (AI) studies in medicine often use small, non-diverse patient cohorts due to data sharing and privacy issues. Federated learning (FL) has emerged as a solution, enabling training across hospitals without direct data sharing. Here, we present FL-PedBrain, an FL platform for pediatric posterior fossa brain tumors, and evaluate its performance on a diverse, realistic, multi-center cohort. Pediatric brain tumors were targeted due to the scarcity of such datasets, even in tertiary care hospitals. Our platform orchestrates federated training for joint tumor classification and segmentation across 19 international sites. FL-PedBrain exhibits less than a 1.5% decrease in classification and a 3% reduction in segmentation performance compared to centralized data training. FL boosts segmentation performance by 20 to 30% on three external, out-of-network sites. Finally, we explore the sources of data heterogeneity and examine FL robustness in real-world scenarios with data imbalances. Federated learning (FL) has emerged as a potential solution to train machine learning models in multiple clinical datasets while preserving patient privacy. Here, the authors develop an MRI-based FL platform for pediatric posterior fossa brain tumors—FL-PedBrain—and evaluate it on a diverse multi-center cohort. [ABSTRACT FROM AUTHOR]

With the ever-growing reliance on polymeric materials for numerous applications, new avenues to induce, design and control degradation are clearly important. Here, we describe a previously unreported approach to controlling enzymatic hydrolysis of high molecular weight branched polymers formed from the new free-radical polymer synthesis strategy transfer-dominated branching radical telomerisation (TBRT). Modifying the chemical nature of TBRT polymers may be accomplished through telogen selection and multi-vinyl taxogen (MVT) design, and we show telogen-driven control of enzyme-catalysed hydrolysis and the impact of careful placement of hydrolytically susceptible groups within readily synthesised MVTs. Our results indicate that utilising conventional free-radical chemistries and unsaturated monomers as feedstocks for highly branched polymer architectures has considerable potential for the design of future materials that degrade into very low molecular weight byproducts at variable and controllable rates. With the ever-growing reliance on polymeric materials for numerous applications, new avenues to induce, design and control degradation are clearly important. Here, the authors report an approach to controlling the enzymatic hydrolysis of high molecular weight branched polymers formed from transfer-dominated branching radical telomerisation, through telogen selection and multi-vinyl taxogen design. [ABSTRACT FROM AUTHOR]

Research on institutional child care consistently has documented detrimental developmental outcomes. However, recent work in Ghana revealed a range in patterns of adjustment among children living in institutional care. The developmental patterns of children living in institutional care often were not significantly different from patterns seen among children living in families. A grounded-theory approach was used to understand Ghanaian adults' perceptions of adjustment of children living in both institutional care and with families, and their beliefs about contributions to positive functioning. Qualitative semi-structured interviews were conducted with 38 caregivers, social workers, and teachers recruited from the Accra region in Ghana. Thematic analysis of responses was used to identify common themes described in the interviews. Interviews with participants revealed beliefs that children may struggle in one or more areas while still having strengths. Having basic needs met, a stable home, and a high level of adult support were the most common factors believed to contribute to positive functioning in both groups of children. Future studies or interventions targeting these areas will likely gain buy-in from stakeholders. Highlights: Ghanaian teachers and caregivers share the belief that children may struggle in certain areas, while thriving in others. The biggest contributors to healthy child development are having their basic needs met, a stable home, and a high level of adult support. Children raised in institutions have more experience problem-solving for themselves than children raised in family care. [ABSTRACT FROM AUTHOR]