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Abstract Microbial biochemistry is central to the pathophysiology of inflammatory bowel diseases (IBD). Improved knowledge of microbial metabolites and their immunomodulatory roles is thus necessary for diagnosis and management. Here, we systematically analyzed the chemical, ecological, and epidemiological properties of ~82k metabolic features in 546 Integrative Human Microbiome Project (iHMP/HMP2) metabolomes, using a newly developed methodology for bioactive compound prioritization from microbial communities. This suggested >1000 metabolic features as potentially bioactive in IBD and associated ~43% of prevalent, unannotated features with at least one well-characterized metabolite, thereby providing initial information for further characterization of a significant portion of the fecal metabolome. Prioritized features included known IBD-linked chemical families such as bile acids and short-chain fatty acids, and less-explored bilirubin, polyamine, and vitamin derivatives, and other microbial products. One of these, nicotinamide riboside, reduced colitis scores in DSS-treated mice. The method, MACARRoN, is generalizable with the potential to improve microbial community characterization and provide therapeutic candidates.

Purpose: This multi-study programme investigated the optimal concentration of l-menthol delivered as an oral mouth rinse to modulate thermo-behaviour during exercise in a hot environment (35 °C). Method: In study 1, 38 participants completed a survey to establish an effective and tolerable range of l-menthol concentration. 31 participants completed an RPE-protocol examining 1. the dose–response effect of l-menthol mouth rinse on exercise performance (n = 16) and 2. the temporal effectiveness of administering l-menthol in an incremental and decremental dosing pattern (n = 15). Power output, heart rate, body core temperature and thermal sensation were reported throughout. Results: The optimal menthol concentration for peak power was between 0.01 and 0.1% (~ 6% increase, P < 0.05) and 0.5% (~ 9% increase, P < 0.05) with respect to control. Work completed was increased at 0.01% (~ 5%, P < 0.05), at 0.1% (~ 3%, P < 0.05) and had a detrimental effect at 0.5% (− 10% decrease, P < 0.05). There were no differences between an ascending dose protocol (0.01 to 0.5%), descending dose protocol (0.5–0.01%) or a constant 0.01% dose protocol. There were no reported differences in body core temperature or heart rate across trials (P > 0.05). Conclusion: The optimal dose of l-menthol when delivered via oral rinsing is between 0.01 and 0.1%. At lower concentrations, l-menthol appears to be less effective and at higher concentrations (> 0.5%) l-menthol appears to elicit greater irritation and may not positively modulate thermo-behaviour during exercise in a hot environment. [ABSTRACT FROM AUTHOR]

Assuming the extrinsic Q-curvature admits a decomposition into the Pfaffian, a scalar conformal submanifold invariant, and a tangential divergence, we prove that the renormalized area of an even-dimensional minimal submanifold of a Poincaré–Einstein manifold can be expressed as a linear combination of its Euler characteristic and the integral of a scalar conformal submanifold invariant. We derive such a decomposition of the extrinsic Q-curvature in dimensions two and four, thereby recovering and generalizing results of Alexakis–Mazzeo and Tyrrell, respectively. We also conjecture such a decomposition for general natural submanifold scalars whose integral over compact submanifolds is conformally invariant, and verify our conjecture in dimensions two and four. Our results also apply to the area of a compact even-dimensional minimal submanifold of an Einstein manifold. [ABSTRACT FROM AUTHOR]

Purpose: The effects of low-intensity exercise, heat-induced hypo-hydration and rehydration on maximal strength and the underlying neurophysiological mechanisms are not well understood. Methods: To assess this, 12 participants took part in a randomised crossover study, in a prolonged (3 h) submaximal (60 W) cycling protocol under 3 conditions: (i) in 45 °C (achieving ~ 5% body mass reduction), with post-exercise rehydration in 2 h (RHY2), (ii) with rehydration across 24 h (RHY24), and (iii) a euhydrated trial in 25 °C (CON). Dependent variables included maximal voluntary contractions (MVC), maximum motor unit potential (MMAX), motor evoked potential (MEPRAW) amplitude and cortical silent period (cSP) duration. Blood–brain-barrier integrity was also assessed by serum Ubiquitin Carboxyl-terminal Hydrolase (UCH-L1) concentrations. All measures were obtained immediately pre, post, post 2 h and 24 h. Results: During both dehydration trials, MVC (RHY2: p < 0.001, RHY24: p = 0.001) and MEPRAW (RHY2: p = 0.025, RHY24: p = 0.045) decreased from pre- to post-exercise. MEPRAW returned to baseline during RHY2 and CON, but not RHY24 (p = 0.020). MEP/MMAX ratio decreased across time for all trials (p = 0.009) and returned to baseline, except RHY24 (p < 0.026). Increased cSP (p = 0.011) was observed during CON post-exercise, but not during RHY2 and RHY24. Serum UCH-L1 increased across time for all conditions (p < 0.001) but was not significantly different between conditions. Conclusion: Our findings demonstrate an increase in corticospinal inhibition after exercise with fluid ingestion, but a decrease in corticospinal excitability after heat-induced hypo-hydration. In addition, low-intensity exercise increases peripheral markers of blood–brain-barrier permeability. [ABSTRACT FROM AUTHOR]

Background: Multidisciplinary care is paramount in patient-specific decision making, especially as pertaining to oral cavity squamous cell cancer (OCSCC) treatment. Protracted surgery-postoperative-radiation (S-PORT) has a detrimental impact on OCSCC patients' outcomes. This study examined the impact of surgeon-radiation oncologist dyads on the treatment of OCSCC, focusing on S-PORT interval and disease specific outcomes. Methods: All OCSCC patients treated in a tertiary cancer center between 2009 to 2017 were included. Patients were categorized into "dyad" and "nondyad" groups defined as whether they were treated by a paired surgeon–radiation oncology team with joint multidisciplinary clinic or shared >30% patient volumes. Univariate and multivariate logistic regression were performed to identify factors associated with a prolonged S-PORT time interval (≥8 weeks). Overall survival and locoregional recurrence were estimated and compared. Results: A total of 444 OCSCC were eligible. Treatment by a dyad was significantly less likely associated with S-PORT ≥ 8 weeks (odds ratio [OR]unadjusted: 0.65; 95% confidence interval [CI] 0.44–0.96; p = 0.03). Obtaining pre-operative radiation oncology consultation also decreased the S-PORT interval. Advanced T-category and the need for free tissue flap reconstruction increased the likelihood of prolonged S-PORT on univariate but not multivariate analysis. No significant differences were observed in overall survival or locoregional recurrence by dyad status nor S-PORT (p > 0.05). Conclusions: Surgeon-radiation oncology dyads significantly minimized time from surgery to postoperative radiation in OCSCC. While improvement in overall survival or locoregional recurrence was not observed, these findings support close knit collaborative multidisciplinary treatment care models, including dyad-based care. [ABSTRACT FROM AUTHOR]

We develop an operational framework, combining relativistic quantum measurement theory with quantum reference frames (QRFs), in which local measurements of a quantum field on a background with symmetries are performed relative to a QRF. This yields a joint algebra of quantum-field and reference-frame observables that is invariant under the natural action of the group of spacetime isometries. For the appropriate class of quantum reference frames, this algebra is parameterised in terms of crossed products. Provided that the quantum field has good thermal properties (expressed by the existence of a KMS state at some nonzero temperature), one can use modular theory to show that the invariant algebra admits a semifinite trace. If furthermore the quantum reference frame has good thermal behaviour (expressed in terms of the properties of a KMS weight) at the same temperature, this trace is finite. We give precise conditions for the invariant algebra of physical observables to be a type II 1 factor. Our results build upon recent work of Chandrasekaran et al. (J High Energy Phys 2023(2): 1–56, 2023. ), providing both a significant mathematical generalisation of these findings and a refined operational understanding of their model. [ABSTRACT FROM AUTHOR]

Background: Cultural gerontology – understanding ageing through the lens of arts and humanities—has emerged as an important element of epistemology of ageing. As a boundary area between geriatric medicine/gerontology and arts/humanities disciplines, joint-working/interdisciplinarity is desirable. This project aims to assess the degree of joint-working manifested in cultural gerontology by authorship and acknowledgements in papers dedicated to cultural gerontology in five journals. Methods: Observational survey of authorship in 5 journals from the founding of the specific sections on cultural gerontology or specific dedicated journals, assessing number of authors, disciplinary identities, and evidence of joint working within cultural gerontology. Results: Of 591 papers, 481 (81%) were single authors. There was a spread of disciplinary affiliations, 247 (41.8%) gerontology/age studies, 169 arts/humanities/social sciences (28.6%) and 133 of uncertain affiliation (22.5%): only 38 papers had a clear indication of joint working across the disciplines (6.4%). In the two geriatric medicine journals, European Geriatric Medicine and Journal of the American Geriatrics Society, authorship was almost exclusively from geriatric medicine/gerontology. There was extremely limited use of acknowledgements. Conclusion: Our study indicates that single authorship is the most frequent mode of peer-reviewed publishing in cultural gerontology, whilst acknowledging that some authors may have scholarly training in multiple fields but are listed as unidisciplinary. Leaders in the field and editors of relevant journals/section need to consider ways of encouraging and recognising joint working, through fuller descriptions of multiple affiliations, brief author biographies, fuller use of acknowledgements and consideration of brief accompanying discussant responses from complementary disciplines. [ABSTRACT FROM AUTHOR]

Purpose: Post-exercise passive heating has been reported to augment adaptations associated with endurance training. The current study evaluated the effect of a 4-week remotely administered, post-exercise passive leg heating protocol, using an electrically heated layering ensemble, on determinants of endurance performance. Methods: Thirty recreationally trained participants were randomly allocated to either a post-exercise passive leg heating (PAH, n = 16) or unsupervised training only control group (CON, n = 14). The PAH group wore the passive heating ensemble for 90–120 min/day, completing a total of 20 (16 post-exercise and 4 stand-alone leg heating) sessions across 4 weeks. Whole-body (peak oxygen uptake, gas exchange threshold, gross efficiency and pulmonary oxygen uptake kinetics), single-leg exercise (critical torque and NIRS-derived muscle oxygenation), resting vascular characteristics (flow-mediated dilation) and angiogenic blood measures (nitrate, vascular endothelial growth factor and hypoxia inducible factor 1−α) were recorded to characterize the endurance phenotype. All measures were assessed before (PRE), at 2 weeks (MID) and after (POST) the intervention. Results: There was no effect of the intervention on test of whole-body endurance capacity, vascular function or blood markers (p > 0.05). However, oxygen kinetics were adversely affected by PAH, denoted by a slowing of the phase II time constant; τ (p = 0.02). Furthermore, critical torque–deoxygenation ratio was improved in CON relative to PAH (p = 0.03). Conclusion: We have demonstrated that PAH had no ergogenic benefit but instead elicited some unfavourable effects on sub-maximal exercise characteristics in recreationally trained individuals. [ABSTRACT FROM AUTHOR]

This paper addresses the controversy between "thin" (i.e. formal and procedural) and "thick" (i.e. substantive) conceptions of the rule of law. It considers the difficulty in specifying which substantive values and principles to incorporate into our understanding of the rule of law if we want a substantive conception. It considers various strategies for organizing this selection and warns against some of them. [ABSTRACT FROM AUTHOR]

Currently, no objective method exists to measure the extent of fibrosis in swallowing musculature in head and neck cancer (HNC) patients. We developed and psychometrically tested a method of quantifying fibrosis volume using magnetic resonance imaging (MRI). The overall aim of this study was to determine if clinical MRI is a reliable tool to measure fibrosis of the pharyngeal musculature in patients with HNC managed with RT and to assess its potential to capture changes in fibrosis over time. Eligible participants were adults with HNC treated with radiation therapy (RT) who received minimally two MRIs and videofluoroscopic swallow (VFS) studies from baseline (pre-RT) up to 1-year post-RT. Two neuroradiologists independently contoured fibrosis volume in batches from MRIs using Vitrea™. Sufficient inter-rater reliability was set at Intraclass Correlation Coefficient (ICC) > 0.75. Two speech-language pathologists independently rated VFSs for swallowing impairment using standardized scales, with discrepancies resolved by consensus. MRI and VFS scores were correlated using Spearman's rank coefficient. Participants included 42 adults (male = 33); mean age 59 (SD = 8.8). ICC (95% Confidence Interval) for fibrosis volume was 0.34 (0, 0.76) for batch one and 0.43 (0, 0.82) for batch two. Consensus meetings were held after each batch. Sufficient reliability was reached by batch three (ICC = 0.95 (0.79, 0.99)). Fibrosis volume increased significantly from 3 to 12 months (mean change = 1.28 mL (SD = 5.21), p = 0.006), as did pharyngeal impairment from baseline to 12 months (mean score change = 3.05 (SD = 3.02), p = 0.003). Fibrosis volume moderately correlated with pharyngeal impairment at 3 and 12 months (0.49, p = 0.004 and 0.59, p = 0.005, respectively). We demonstrated a reliable measure of fibrosis volume in swallowing musculature from existing clinical MRIs and identified that larger fibrosis volume was associated with worse swallowing function. The reliable capture of fibrosis volume offers a pragmatic method for early detection of fibrosis and concomitant dysphagia. [ABSTRACT FROM AUTHOR]

The link between the oral microbiome and neurodevelopmental disorders remains a compelling hypothesis, still requiring confirmation in large-scale datasets. Leveraging over 7000 whole-genome sequenced salivary samples from 2025 US families with children diagnosed with autism spectrum disorders (ASD), our cross-sectional study shows that the oral microbiome composition can discriminate ASD subjects from neurotypical siblings (NTs, AUC = 0.66), with 108 differentiating species (q < 0.005). The relative abundance of these species is highly correlated with cognitive impairment as measured by Full-Scale Intelligence Quotient (IQ). ASD children with IQ < 70 also exhibit lower microbiome strain sharing with parents (p < 10−6) with respect to NTs. A two-pronged functional enrichment analysis suggests the contribution of enzymes from the serotonin, GABA, and dopamine degradation pathways to the distinct microbial community compositions observed between ASD and NT samples. Although measures of restrictive eating diet and proxies of oral hygiene show relatively minor effects on the microbiome composition, the observed associations with ASD and IQ may still represent unaccounted-for underlying differences in lifestyle among groups. While causal relationships could not be established, our study provides substantial support to the investigation of oral microbiome biomarkers in ASD. Here, Manghi et al. identify potential salivary microbial biomarkers for autism through a large-scale metagenomic analysis of 2,000 families, revealing shifts in neurotransmitter-related pathways [ABSTRACT FROM AUTHOR]

Hydrologic tracer, borehole log and geophysical data provide new insight into recharge sources and pathways to the semi-confined Memphis aquifer in the Davis wellfield, Memphis, Tennessee, U.S.A. New data and recent studies highlight the importance of faults as potential pathways for the migration of modern water into the Memphis aquifer, an important regional public, industrial, and agricultural water supply. Geochemical and environmental tracer data collected over the past 28 years, combined with hydrologic, stratigraphic, and structural data, were used to evaluate changes in water quality and different recharge pathways to the Memphis aquifer. Assessment of stratigraphic and structural relationships argue for the wellfield being bound by a fault along the bluff line (west) and another fault or faults along the eastern and southeastern margins. Modern water recharge (< 60 years old) occurs through the fault along the western boundary of the wellfield, whereas modern water and, seasonally, deep-seated (helium-bearing) fluids recharge along the fault on the southeastern margin. Each recharge source and pathway present different vulnerabilities, suggesting that the role of faults in wellfields within active tectonic regions needs to be assessed. [ABSTRACT FROM AUTHOR]

We formulate a geometric measurement theory of dynamical classical systems possessing both continuous and discrete degrees of freedom. The approach is covariant with respect to choices of clocks and naturally incorporates laboratories. The latter are embedded symplectic submanifolds of an odd-dimensional symplectic structure. When suitably defined, symplectic geometry in odd dimensions is exactly the structure needed for covariance. A fundamentally probabilistic viewpoint allows classical supergeometries to describe discrete dynamics. We solve the problem of how to construct probabilistic measures on supermanifolds given a (possibly odd dimensional) supersymplectic structure. This relies on a superanalog of the Hodge star for differential forms and a description of probabilities by convex cones. We also show how stochastic processes such as Markov chains can be described by supergeometry. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of taurine supplementation on sweating and core temperature responses, including the transition from compensable to uncompensable heat stress, during prolonged low-intensity exercise of a fixed-heat production (~ 200W/m2) in hot conditions (37.5 °C), at both fixed and incremental vapour-pressure. Methods: Fifteen females (n = 3) and males (n = 12; 27 ± 5 years, 78 ± 9 kg, V ˙ O2max 50.3 ± 7.8 mL/kg/min), completed a treadmill walking protocol (~ 200W/m2 heat production [Ḣprod]) in the heat (37.5 ± 0.1 °C) at fixed-(16-mmHg) and ramped-humidity (∆1.5-mmHg/5-min) following 1 week of oral taurine supplementation (50 mg/kg/bm) or placebo, in a double-blind, randomised, cross-over design. Participants were assessed for whole-body sweat loss (WBSL), local sweat rate (LSR), sweat gland activation (SGA), core temperature (Tcore), breakpoint of compensability (Pcrit) and calorimetric heat transfer components. Plasma volume and plasma taurine concentrations were established through pre- and post-trial blood samples. Results: Taurine supplementation increased WBSL by 26.6% and 5.1% (p = 0.035), LSR by 15.5% and 7.8% (p = 0.013), SGA (1 × 1 cm) by 32.2% and 29.9% (p < 0.001) and SGA (3 × 3 cm) by 22.1% and 17.1% (p = 0.015) during the fixed- and ramped-humidity exercise periods, respectively. Evaporative heat loss was enhanced by 27% (p = 0.010), heat-storage reduced by 72% (p = 0.024) and Pcrit was greater in taurine vs placebo (25.0-mmHg vs 21.7-mmHg; p = 0.002). Conclusion: Taurine supplementation increased sweating responses during fixed Ḣprod in hot conditions, prior to substantial heat strain and before the breakpoint of compensability, demonstrating improved thermoregulatory capacity. The enhanced evaporative cooling and reduced heat-storage delayed the subsequent upward inflection in Tcore—represented by a greater Pcrit—and offers a potential dietary supplementation strategy to support thermoregulation. [ABSTRACT FROM AUTHOR]

Purpose: Caffeine is a commonly used ergogenic aid for endurance events; however, its efficacy and safety have been questioned in hot environmental conditions. The aim of this study was to investigate the effects of acute caffeine supplementation on cycling time to exhaustion and thermoregulation in the heat. Methods: In a double-blind, randomised, cross-over trial, 12 healthy caffeine-habituated and unacclimatised males cycled to exhaustion in the heat (35 °C, 40% RH) at an intensity associated with the thermoneutral gas exchange threshold, on two separate occasions, 60 min after ingesting caffeine (5 mg/kg) or placebo (5 mg/kg). Results: There was no effect of caffeine supplementation on cycling time to exhaustion (TTE) (caffeine; 28.5 ± 8.3 min vs. placebo; 29.9 ± 8.8 min, P = 0.251). Caffeine increased pulmonary oxygen uptake by 7.4% (P = 0.003), heat production by 7.9% (P = 0.004), whole-body sweat rate (WBSR) by 21% (P = 0.008), evaporative heat transfer by 16.5% (P = 0.006) and decreased estimated skin blood flow by 14.1% (P < 0.001) compared to placebo. Core temperature was higher by 0.6% (P = 0.013) but thermal comfort decreased by − 18.3% (P = 0.040), in the caffeine condition, with no changes in rate of perceived exertion (P > 0.05). Conclusion: The greater heat production and storage, as indicated by a sustained increase in core temperature, corroborate previous research showing a thermogenic effect of caffeine ingestion. When exercising at the pre-determined gas exchange threshold in the heat, 5 mg/kg of caffeine did not provide a performance benefit and increased the thermal strain of participants. [ABSTRACT FROM AUTHOR]

Purpose: Power output at the moderate-to-heavy-intensity transition decreases during prolonged exercise, and resilience to this has been termed 'durability'. The purpose of this study was to assess the relationship between durability and the effect of prolonged exercise on severe-intensity performance, and explore intramuscular correlates of durability. Methods: On separate days, 13 well-trained cyclists and triathletes (V̇O2peak, 57.3 ± 4.8 mL kg−1 min−1; training volume, 12 ± 2.1 h week−1) undertook an incremental test and 5-min time trial (TT) to determine power output at the first ventilatory threshold (VT1) and severe-intensity performance, with and without 150-min of prior moderate-intensity cycling. A single resting vastus lateralis microbiopsy was obtained. Results: Prolonged exercise reduced power output at VT1 (211 ± 40 vs. 198 ± 39 W, ∆ -13 ± 16 W, ∆ -6 ± 7%, P = 0.013) and 5-min TT performance (333 ± 75 vs. 302 ± 63 W, ∆ -31 ± 41 W, ∆ -9 ± 10%, P = 0.017). The reduction in 5-min TT performance was significantly associated with durability of VT1 (rs = 0.719, P = 0.007). Durability of VT1 was not related to vastus lateralis carnosine content, citrate synthase activity, or complex I activity (P > 0.05). Conclusion: These data provide the first direct support that durability of the moderate-to-heavy-intensity transition is an important performance parameter, as more durable athletes exhibited smaller reductions in 5-min TT performance following prolonged exercise. We did not find relationships between durability and vastus lateralis carnosine content, citrate synthase activity, or complex I activity. [ABSTRACT FROM AUTHOR]

Background: Gut microbiome modulation to boost antitumor immune responses is under investigation. Methods: ROMA-2 evaluated the microbial ecosystem therapeutic (MET)-4 oral consortia, a mixture of cultured human stool-derived immune-responsiveness associated bacteria, given with chemoradiation (CRT) in HPV-related oropharyngeal cancer patients. Co-primary endpoints were safety and changes in stool cumulative MET-4 taxa relative abundance (RA) by 16SRNA sequencing. Stools and plasma were collected pre/post-MET-4 intervention for microbiome and metabolome analysis. Results: Twenty-nine patients received ≥1 dose of MET-4 and were evaluable for safety: drug-related adverse events (AEs) occurred in 13/29 patients: all grade 1–2 except one grade 3 (diarrhea). MET-4 was discontinued early in 7/29 patients due to CRT-induced toxicity, and in 1/29 due to MET-4 AEs. Twenty patients were evaluable for ecological endpoints: there was no increase in stool MET-4 RA post-intervention but trended to increase in stage III patients (p = 0.06). MET-4 RA was higher in stage III vs I-II patients at week 4 (p = 0.03) and 2-month follow-up (p = 0.01), which correlated with changes in plasma and stool targeted metabolomics. Conclusions: ROMA-2 did not meet its primary ecologic endpoint, as no engraftment was observed in the overall cohort. Exploratory findings of engraftment in stage III patients warrants further investigation of microbiome interventions in this subgroup. [ABSTRACT FROM AUTHOR]

Background: Therapeutic plasma exchange (TPE) is utilised in the management of a limited number of paediatric renal conditions. Despite its widespread acceptance and advancements in the practice of apheresis, there remains a paucity of data pertaining to paediatrics. We present a large retrospective review of our cohort of paediatric patients undergoing TPE for renal indications, outlining their outcomes and complications. Methods: A retrospective chart review was conducted for all patients (under 16 years) undergoing TPE for renal conditions between January 2002 and June 2019 in Ireland. Demographic and clinical data were extracted, with patients anonymised and stratified according to their pathology. Results: A total of 58 patients were identified. A total of 1137 exchanges were performed using heparin sodium anticoagulation. The median age was 35.5 months (IQR 18–110 months). The leading indication was neurological involvement in Shiga toxin–producing Escherichia coli haemolytic uraemic syndrome (STEC-HUS) (n = 29). Complications (minor or major) occurred in 65.5% (n = 38) of patients, with most experiencing minor complications 58.6% (n = 34). Asymptomatic hypocalcaemia was the most common complication in 43.1% (n = 25). Conclusions: Our experience of TPE, spanning 1137 exchanges, proved a safe, well-tolerated therapy. Most complications were minor, and with therapy conducted in specialised centres, there are very low levels of adverse events. [ABSTRACT FROM AUTHOR]

We present an operationally motivated treatment of quantum reference frames in the setting that the frame is a covariant positive operator valued measure (POVM) on a finite homogeneous space, generalising the principal homogeneous spaces studied in previous work. We focus on the case that the reference observable is the canonical covariant projection valued measure on the given space, and show that this gives rise to a rank-one covariant POVM on the group, which can be seen as a system of coherent states. [ABSTRACT FROM AUTHOR]

Microbial biochemistry is central to the pathophysiology of inflammatory bowel diseases (IBD). Improved knowledge of microbial metabolites and their immunomodulatory roles is thus necessary for diagnosis and management. Here, we systematically analyzed the chemical, ecological, and epidemiological properties of ~82k metabolic features in 546 Integrative Human Microbiome Project (iHMP/HMP2) metabolomes, using a newly developed methodology for bioactive compound prioritization from microbial communities. This suggested >1000 metabolic features as potentially bioactive in IBD and associated ~43% of prevalent, unannotated features with at least one well-characterized metabolite, thereby providing initial information for further characterization of a significant portion of the fecal metabolome. Prioritized features included known IBD-linked chemical families such as bile acids and short-chain fatty acids, and less-explored bilirubin, polyamine, and vitamin derivatives, and other microbial products. One of these, nicotinamide riboside, reduced colitis scores in DSS-treated mice. The method, MACARRoN, is generalizable with the potential to improve microbial community characterization and provide therapeutic candidates. Synopsis: MACARRoN combines ecological and epidemiological metrics to prioritize metabolic features with potential bioactivity in a phenotype of interest. Its application to inflammatory bowel disease (IBD) prioritizes both previously IBD-linked and less-explored microbiome-associated metabolites. Metabolic features that covary among conditions tend to be closer in mass and chemically homogeneous, pointing to underlying biochemical relationships. MACARRoN integrates metabolic feature prevalence, covariance, abundance with respect to an identified metabolite, and extent of perturbation to prioritize actionable, phenotype-associated features from untargeted metabolomics data. MACARRoN prioritized ~1,000 chemically diverse, stool-derived features as IBD-associated, including known IBD biomarkers and several unannotated features that covary with them. Newly IBD-linked metabolic features included microbial polyamines, nicotinamide riboside (shown here to reduce colitis in DSS-treated mice), and novel putatively microbially-derived bilirubin compounds. MACARRoN combines ecological and epidemiological metrics to prioritize metabolic features with potential bioactivity in a phenotype of interest. Its application to inflammatory bowel disease (IBD) prioritizes both previously IBD-linked and less-explored microbiome-associated metabolites. [ABSTRACT FROM AUTHOR]

China has reconfigured the global value chains of a wide range of commodities. This includes carrageenan, a polysaccharide extracted from specific types of red seaweeds used as a gelling and thickening agent in a wide range of applications. In the past 20 years, China has moved to centre stage in the global carrageenan processing sector, with wide-ranging implications for seaweed producing nations and farmers. This is especially the case for Indonesia, a pivotal carrageenan seaweeds producer that exports almost all seaweed to China, cemented by large Chinese investments in processing in Indonesia. Despite the importance, there is a dearth of studies on the Chinese domestic industry and associated trade and investment flows. This study fills the gap by triangulating a range of detailed industry, statistical and interview data, in multiple language sources. It finds that Chinese trade and investment linkages is of net benefit to Indonesia but that Indonesian government agencies at both central and local levels can begin to introduce terms in their favour. [ABSTRACT FROM AUTHOR]

Introduction: Neoadjuvant therapy is an essential component of multimodality therapy for locally advanced breast adenocarcinoma (BC). Complete pathologic response (pCR) is a useful surrogate for long-term oncologic outcome. Aim: To assess the association between clinicopathologic, molecular and immunological markers and treatment response to neoadjuvant therapy in BC. Methods: BC patients undergoing neoadjuvant therapy were identified from a prospectively maintained institutional database. Serum haematological/biochemical values, histopathologic, immunohistochemical data and TNM stage were obtained from electronic records. Patients were categorised into complete responders vs non-complete responders and responders vs non-responders. Statistical analysis was performed via SPSS. Results: Overall, 299 BC patients were included. The average age was 49.8 ± 11.5 years. A pCR was evident in 22.6% (n = 69). pCR was associated with early T stage and non-luminal subtypes (HER2 enriched [HER2 +] and triple negative [TNBC]). The neutrophil–lymphocyte ratio (NLR) pre-operatively was lower in patients with a pCR (p = 0.02). The lymphocyte-CRP ratio (LCR) was also slightly reduced in responders (p = 0.049) at diagnosis. A pre-op NLR greater than 2 was not found to be a significant predictive factor (p = 0.071) on multivariable logistic regression analysis. T stage at diagnosis (p = 0.024), N stage (p = 0.001) and breast cancer subtype (p = 0.0001) were also determined to be significant predictive factors of complete response. Conclusion: pCR was more likely in patients with less advanced disease in BC. The presence of HER2 + or TNBC in BC also increases the likelihood of pCR. Neoadjuvant therapy stimulates the systemic inflammatory response; however, a reduced baseline NLR may be associated with increased pCR. Confirmation with larger datasets is required. [ABSTRACT FROM AUTHOR]

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This study employed aerial surveys to quantify the spatial and temporal abundance of the whitespotted eagle ray, Aetobatus narinari, and the giant manta ray, Mobula birostris, in southeast Florida. Aetobatus narinari abundance did not differ along the north-south axis of the coast, whereas M. birostris was more abundant at lower latitudes. Similarly, A. narinari did not exhibit any seasonal difference in abundance, whereas M. birostris was more abundant during December and February. Neither species exhibited a clear trend in abundance over the study period (2014–2021). In addition, the abundance of both species failed to correlate with water temperature, chlorophyll-a concentration, or photoperiod. Both M. birostris and A. narinari are protected species in Florida state waters, and M. birostris is designated as threatened under the US Endangered Species Act. In addition, both species are classified by the IUCN as endangered worldwide. Insufficient data exist to establish critical habitat designations for M. birostris so that the provided information on their distribution and abundance is useful for the development of effective management. [ABSTRACT FROM AUTHOR]

TDP-43 is an aggregation-prone protein which accumulates in the hallmark pathological inclusions of amyotrophic lateral sclerosis (ALS). However, the analysis of deeply phenotyped human post-mortem samples has shown that TDP-43 aggregation, revealed by standard antibody methods, correlates poorly with symptom manifestation. Recent identification of cryptic-splicing events, such as the detection of Stathmin-2 (STMN-2) cryptic exons, are providing evidence implicating TDP-43 loss-of-function as a potential driving pathomechanism but the temporal nature of TDP-43 loss and its relation to the disease process and clinical phenotype is not known. To address these outstanding questions, we used a novel RNA aptamer, TDP-43APT, to detect TDP-43 pathology and used single molecule in situ hybridization to sensitively reveal TDP-43 loss-of-function and applied these in a deeply phenotyped human post-mortem tissue cohort. We demonstrate that TDP-43APT identifies pathological TDP-43, detecting aggregation events that cannot be detected by classical antibody stains. We show that nuclear TDP-43 pathology is an early event, occurring prior to cytoplasmic accumulation and is associated with loss-of-function measured by coincident STMN-2 cryptic splicing pathology. Crucially, we show that these pathological features of TDP-43 loss-of-function precede the clinical inflection point and are not required for region specific clinical manifestation. Furthermore, we demonstrate that gain-of-function in the form of extensive cytoplasmic accumulation, but not loss-of-function, is the primary molecular correlate of clinical manifestation. Taken together, our findings demonstrate implications for early diagnostics as the presence of STMN-2 cryptic exons and early TDP-43 aggregation events could be detected prior to symptom onset, holding promise for early intervention in ALS. [ABSTRACT FROM AUTHOR]

Invasive bacterial disease is associated with significant morbidity and mortality. In winter 2022, there was an apparent increased rate of invasive bacterial disease compared to preceding years. Cross-site retrospective analysis of the three Children's Health Ireland (CHI) hospitals looking at children admitted between 1st October 2022–31st December 2022 (Q4) with community-acquired invasive bacterial disease, defined as an abscess in a normally sterile site in the head, neck and chest or isolation or PCR detection of Streptococcus pneumoniae, Neisseria meningitidis, Streptococcus pyogenes (Group A streptococcus) or Haemophilus influenzae from a normally sterile site. Case numbers were compared to Q4 in each of 2018–2021. Eighty-two children met the case definition in Q4 2022 vs 97 (Q4 2018–2021). In 2022, 42/82 (51%) were female, median age 3.75 years (1.5–8.25 years). Only 2 (2%) were immunosuppressed and 2 others (2%) had underlying neurodisability. Fifty (61%) were admitted on second or subsequent presentation to a healthcare setting. Fifty-six (68%) had an abscess in a sterile site. Bloodstream infection (positive blood culture or PCR: 24 (29%)) was the most common site of infection, followed by neck 22 (27%) and intracranial 12 (15%). Group A streptococcus (GAS) 27 (33%) was the most common organism isolated. Seven cases (9%) died in 2022 compared to 2 patients (2%) from 2018 to 2021 (p < 0.05). More children had Paediatric Overall Performance Category (POPC) scores > 1 in 2022 than 2018–2021 (p = 0.003). Conclusion: Invasive bacterial diseases increased in Q4 2022 with higher morbidity and mortality than in the preceding 4 years. Group A streptococcal infection was the most significant organism in 2022. What is known: • Invasive bacterial disease is the leading cause of childhood mortality globally. • There was an increase in cases of invasive Group A streptococcus infections reported in many countries (including Ireland) during the winter of 2022/23. What is new: • Head, neck and chest abscesses increased in Q4 of 2022 compared to the previous 4 years combined. • Invasive bacterial infections in Q4 of 2022 were associated with higher rates of mortality (9%), paediatric intensive care unit (PICU) admission (24%) and requirement for surgical drainage or intervention (67%) than in the preceding years. [ABSTRACT FROM AUTHOR]

New neutrino–nucleus interaction cross-section measurements are required to improve nuclear models sufficiently for future long baseline neutrino experiments to meet their sensitivity goals. A time projection chamber (TPC) filled with a high-pressure gas is a promising detector to characterise the neutrino sources used for such experiments. A gas-filled TPC is ideal for measuring low-energy particles, which travel further in gas than in solid or liquid detectors and using high-pressure increases the target density, resulting in more neutrino interactions. We examine the suitability of multiwire proportional chambers (MWPCs) from the ALICE TPC for use as the readout chambers of a high-pressure gas TPC. These chambers were previously operated at atmospheric pressure. We report the successful operation of an ALICE TPC outer readout chamber (OROC) at pressures up to 4.2 bar absolute (barA) with Ar-CH 4 mixtures with a CH 4 content between 2.8 and 5.0%, and so far up to 4 bar absolute with Ar-CO 2 (90-10). The charge gain of the OROC was measured with signals induced by an 55 Fe source. The largest gain achieved at 4.2 bar was (29 ± 1) · 10 3 in Ar-CH 4 with 4.0% CH 4 with an anode voltage of 2975 V . In Ar-CO 2 with 10% CO 2 at 4 barA, a gain of (4.2 ± 0.1) · 10 3 was observed with anode voltage 2975 V . We extrapolate that at 10 barA, an interesting pressure for future neutrino experiments, a gain of 5000 in Ar-CO 2 with 10% CO 2 (10,000 in Ar-CH 4 with ∼ 4 % CH 4 ) may be achieved with anode voltage of 4.6 kV ( ∼ 3.6 kV ). [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC), a highly lethal disease with limited therapeutic options, may benefit from repurposing of FDA-approved drugs in preventive or interceptive strategies in high-risk populations. Previous animal studies demonstrated that the use of metformin and statins as single agents at relatively high doses restrained PDAC development. Here, four-week-old mice expressing KrasG12D in all pancreatic lineages (KC mice) and fed an obesogenic high fat, high calorie diet that promotes early PDAC development were randomized onto low dosage metformin, simvastatin, or both drugs in combination administered orally. Dual treatment attenuated weight gain, fibro-inflammation, and development of advanced PDAC precursor lesions (pancreatic intraepithelial neoplasia [PanIN]-3) in male KC mice, without significant effect in females or when administered individually. Dual-treated KC mice had reduced proliferation of PanIN cells and decreased transcriptional activity of the Hippo effectors, YAP and TAZ, which are important regulators of PDAC development. Metformin and simvastatin also synergistically inhibited colony formation of pancreatic cancer cells in vitro. Together, our data demonstrated that a combination of low doses of metformin and simvastatin inhibits PDAC development and imply that both drugs are promising agents for being tested in clinical trials for preventing pancreatic cancer progression. [ABSTRACT FROM AUTHOR]

Purpose: Prescribing NAC for breast cancer is a pragmatic treatment strategy for several reasons; however, certain patients suffer chemotherapy-induced toxicities. Unfortunately, identifying patients at risk of toxicity often proves challenging. MiRNAs are small non-coding RNA molecules which modulate genetic expression. The aim of this study was to determine whether circulating miRNAs are sensitive biomarkers that can identify the patients likely to suffer treatment-related toxicities to neoadjuvant chemotherapy (NAC) for primary breast cancer. Methods: This secondary exploratory from the prospective, multicentre translational research trial (CTRIAL ICORG10/11–NCT01722851) recruited 101 patients treated with NAC for breast cancer, from eight treatment sites across Ireland. A predetermined five miRNAs panel was quantified using RQ-PCR from patient bloods at diagnosis. MiRNA expression was correlated with chemotherapy-induced toxicities. Regression analyses was performed using SPSS v26.0. Results: One hundred and one patients with median age of 55 years were recruited (range: 25–76). The mean tumour size was 36 mm and 60.4% had nodal involvement (n = 61) Overall, 33.7% of patients developed peripheral neuropathies (n = 34), 28.7% developed neutropenia (n = 29), and 5.9% developed anaemia (n = 6). Reduced miR-195 predicted patients likely to develop neutropenia (P = 0.048), while increased miR-10b predicted those likely to develop anaemia (P = 0.049). Increased miR-145 predicted those experiencing nausea and vomiting (P = 0.019), while decreased miR-21 predicted the development of mucositis (P = 0.008). Conclusion: This is the first study which illustrates the value of measuring circulatory miRNA to predict patient-specific toxicities to NAC. These results support the ideology that circulatory miRNAs are biomarkers with utility in predicting chemotherapy toxicity as well as treatment response. [ABSTRACT FROM AUTHOR]

We establish the Minimal Model Program for arithmetic threefolds whose residue characteristics are greater than five. In doing this, we generalize the theory of global F-regularity to mixed characteristic and identify certain stable sections of adjoint line bundles. Finally, by passing to graded rings, we generalize a special case of Fujita's conjecture to mixed characteristic. [ABSTRACT FROM AUTHOR]

This study explores factors associated with participation in moderate physical activity and muscle strengthening activity in adults with autism receiving state services (age: 18–78 years). Researchers analyzed the National Core Indicators-In Person Survey (2017–2018) data using multilevel mixed effects logistic regression. Older adults on the autism spectrum engaged in both moderate physical activity and muscle strengthening activity less often than younger adults on the autism spectrum (OR 0.99; p < 0.05; OR 0.98; p < 0.001). Individuals reportedly in fair/poor health had 50% lower odds of engaging in moderate physical activity and 30% lower odds of engaging in muscle strengthening compared to those in good/ excellent health (OR 0.50; p < 0.001; OR 0.70; p < 0.001). Moderate physical activity/muscle strengthening initiatives may help foster this group's healthy aging. [ABSTRACT FROM AUTHOR]

The special education eligibility category that has come to be most commonly associated with Attention-Deficit Hyperactivity Disorder (ADHD) in recent years is Other Health Impairment (OHI). However, the eligibility criteria for the OHI disability category have been criticized for being especially vague, given that the disability category incorporates a wide range of health impairments without providing any additional specificity. Because states have the latitude to utilize more specific eligibility criteria than what is provided at the federal level, the purpose of the current study was to review state-level special education eligibility criteria for OHI, with particular interest in identifying the degree to which eligibility guidance exists specific to students with ADHD and the extent to which this guidance varies across states. Results suggested that wide state variation exists regarding eligibility guidance, with 22% of states utilizing the federal definition and only 14% of states providing elaboration regarding all three components of the federal definition. Whereas it was most common for states to provide additional guidance surrounding what is needed to establish that a student has a health impairment, less than half of states provided specific guidance surrounding the other two components of the federal definition. Implications for policy and practice are discussed. [ABSTRACT FROM AUTHOR]

An extensive water level survey of the water-table aquifer (i.e., shallow aquifer) within Shelby County, Tennessee, was conducted in the dry (fall 2020) and wet (spring 2021) seasons. Water-table surfaces were generated using cokriging to observe seasonal differences to identify anomalous water-table depressions, indicative of an underlying aquitard breach. Seasonal differences were attributed to non-coincident control and timing between the surveys and when optimum dry (fall) and wet (spring) conditions existed, as observed through comparisons with continuous historical water levels from 12 shallow monitoring wells. Additionally, data from fall 2020 were compared to previous studies in 2005 and 2015 to determine decadal changes in levels and shape of the water-table surface which were mostly attributed to changes in data control and potential climate variations. A prediction error map was generated from the 2020 dataset to identify areas of the county with high-prediction error (>7.0 m) to offer guidance on where future well control would be optimal. [ABSTRACT FROM AUTHOR]

This study demonstrates the high performance of deep learning in identification of body regions covering the entire human body from magnetic resonance (MR) and computed tomography (CT) axial images across diverse acquisition protocols and modality manufacturers. Pixel-based analysis of anatomy contained in image sets can provide accurate anatomic labeling. For this purpose, a convolutional neural network (CNN)–based classifier was developed to identify body regions in CT and MRI studies. Seventeen CT (18 MRI) body regions covering the entire human body were defined for the classification task. Three retrospective datasets were built for the AI model training, validation, and testing, with a balanced distribution of studies per body region. The test datasets originated from a different healthcare network than the train and validation datasets. Sensitivity and specificity of the classifier was evaluated for patient age, patient sex, institution, scanner manufacturer, contrast, slice thickness, MRI sequence, and CT kernel. The data included a retrospective cohort of 2891 anonymized CT cases (training, 1804 studies; validation, 602 studies; test, 485 studies) and 3339 anonymized MRI cases (training, 1911 studies; validation, 636 studies; test, 792 studies). Twenty-seven institutions from primary care hospitals, community hospitals, and imaging centers contributed to the test datasets. The data included cases of all sexes in equal proportions and subjects aged from 18 years old to + 90 years old. Image-level weighted sensitivity of 92.5% (92.1–92.8) for CT and 92.3% (92.0–92.5) for MRI and weighted specificity of 99.4% (99.4–99.5) for CT and 99.2% (99.1–99.2) for MRI were achieved. Deep learning models can classify CT and MR images by body region including lower and upper extremities with high accuracy. [ABSTRACT FROM AUTHOR]

Purpose: Interstitial lung disease (ILD) is the most common non-musculoskeletal manifestation of idiopathic inflammatory myopathies (IIM). Identification of body composition change may enable early intervention to improve prognosis. We investigated muscle quantity and quality derived from cross-sectional imaging in IIM, and its relationship to ILD severity. Methods: A retrospective cohort study assessing IIM of ILD patients (n = 31) was conducted. Two datasets separated in time were collected, containing demographics, biochemical data, pulmonary function testing and thoracic CT data. Morphomic analysis of muscle quantity (cross-sectional area) and quality (density in Hounsfield Units) on thoracic CT were analysed utilising a web-based tool allowing segmentation of muscle and fat. Bilateral erector spinae and pectoralis muscle (ESM&PM) were measured at defined vertebral levels. Results: FVC and DLCO decreased but within acceptable limits of treatment response (FVC: 83.7–78.7%, p < 0.05, DLCO 63.4–60.6%, p < 0.05). The cross-sectional area of the PM and ESM increased (PM: 39.8 to 40.7 cm2, p = 0.491; ESM: 35.2 to 39.5 cm2, p = 0.098). Density significantly fell for both the PM and ESM (PM: 35.3–31 HU, p < 0.05; ESM: 38–33.7, p < 0.05). Subcutaneous fat area increased from 103.9 to 136.1 cm2 (p < 0.05), while the visceral fat area increased but not reaching statistical significance. The change in PM density between time points demonstrated an inverse correlation with DLCO (p < 0.05, R = − 0.49). Conclusion: Patients with IIM ILD demonstrated significant body composition changes on CT imaging unlikely to be detected by traditional measurement tools. An increase in muscle area with an inverse decrease in density suggests poor muscle quality. [ABSTRACT FROM AUTHOR]

Inhibition of bacterial cell wall synthesis by antibiotics such as β-lactams is thought to cause explosive lysis through loss of cell wall integrity. However, recent studies on a wide range of bacteria have suggested that these antibiotics also perturb central carbon metabolism, contributing to death via oxidative damage. Here, we genetically dissect this connection in Bacillus subtilis perturbed for cell wall synthesis, and identify key enzymatic steps in upstream and downstream pathways that stimulate the generation of reactive oxygen species through cellular respiration. Our results also reveal the critical role of iron homeostasis for the oxidative damage-mediated lethal effects. We show that protection of cells from oxygen radicals via a recently discovered siderophore-like compound uncouples changes in cell morphology normally associated with cell death, from lysis as usually judged by a phase pale microscopic appearance. Phase paling appears to be closely associated with lipid peroxidation. Inhibition of bacterial cell wall synthesis by β-lactam antibiotics results in a loss of cell wall integrity, but cells die via a combination of downstream events involving metabolic perturbations and oxidative damage. Here, Kawai et al. identify key enzymatic steps that stimulate the generation of reactive oxygen species and highlight the role of iron homeostasis in the lethal effects mediated by oxidative damage. [ABSTRACT FROM AUTHOR]

Introduction: Acute severe elevation of blood pressure (BP) is a common clinical event, that can present as hypertensive emergency (HTNE) and hypertensive urgency (HTNU). HTNE results in life-threatening target organ damage, including myocardial infarction, pulmonary edema, stroke, and acute kidney injury. It is associated with high utilization of healthcare and increased cost. HTNU is high BP without acute serious complications. Aim: The purpose of this review was to examine the clinical-epidemiological characteristics of patients with HTNE and propose a risk stratification framework to differentiate between the two conditions, since prognosis, setting of therapy and treatment is vastly different. Methods: Systematic review. Results: Fourteen full-text studies were included in this review. In comparison with HTNU, patients with HTNE had higher mean systolic (mean difference 2.413, 95% CI 0.477, 4.350) and diastolic BP (mean difference 2.043, 95% CI 0.624, 3.461). HTNE were more prevalent in men (OR 1.390, 95% CI 1.207, 1.601), older adults (mean difference 5.282, 95% CI 3.229, 7.335) and those with diabetes (OR 1.723, 95% CI 1.485, 2.000). Non-adherence to BP medications (OR 0.939, 95% CI 0.647, 1.363) and unawareness of hypertension diagnosis (OR 0.807, 95% CI 0.564, 1.154) did not elevate the risk of HTNE. Conclusions: Systolic and diastolic BP are marginally higher in patients with HTNE. Given that these differences are not clinically significant, other epidemiological and medical characteristics (older age, male sex, cardiometabolic comorbidities) as well as patient's presentation should be considered to differentiate between HTNU and HTNE. [ABSTRACT FROM AUTHOR]

The complex set of challenges that middle-aged adults encounter emphasizes a need for mental health interventions that promote resilience and positive outcomes. The present study evaluated whether an online, self-guided social intelligence training (SIT) program (8 h) improved midlife adults' daily well-being and emotion regulation in the context of their own naturalistic everyday environment. A randomized controlled trial was conducted with 230 midlife adults allocated into either a SIT program or an attentional control (AC) condition that focused on healthy lifestyle education. Intent-to-treat analyses examined two bursts of 14-day daily surveys that participants completed pre- and post-treatment. Multilevel models evaluated pre-to post-treatment changes in mean positive and negative affect, as well as daily emotional reactivity to stressors and responsiveness to uplifts. Compared to the AC group, those in the SIT program reported improvements (i.e., decreases) in mean negative affect, positive emotional reactivity to daily stressors (i.e., smaller decreases in positive affect on stressor days), and negative emotional responsiveness to uplifts (i.e., lower negative affect on days without uplifts). Our discussion considers potential mechanisms underlying these improvements, highlights downstream effects on midlife functioning, and elaborates on how online delivery of the SIT program increases its potential for positive outcomes across adulthood. ClinicalTrials.gov Identifier: NCT03824353. [ABSTRACT FROM AUTHOR]

This paper proves a general Uhlenbeck compactness theorem for sequences of solutions of Yang–Mills flow on Riemannian manifolds of dimension n ≥ 4 , including rectifiability of the singular set at finite or infinite time. [ABSTRACT FROM AUTHOR]

Background: Drug–drug interactions (DDIs) can lead to medication-related harm, and the older population is at greatest risk. We conducted a systematic review and meta-analysis to estimate DDI prevalence and identify common DDIs in older community-dwelling adults. Methods: PubMed and EMBASE were searched for observational studies published between 01/01/2010 and 10/05/2021 reporting DDI prevalence in community-dwelling individuals aged ≥ 65 years. Nursing home and inpatient hospital studies were excluded. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool. Meta-analysis was performed using a random-effects model with logit transformation. Heterogeneity was evaluated using Cochran's Q and I2. DDI prevalence and 95% confidence intervals (CIs) are presented. All analyses were performed in R (version 4.1.2). Results: There were 5144 unique articles identified. Thirty-three studies involving 17,011,291 community-dwelling individuals aged ≥ 65 years met inclusion criteria. Thirty-one studies reported DDI prevalence at the study-participant level, estimates ranged from 0.8% to 90.6%. The pooled DDI prevalence was 28.8% (95% CI 19.3–40.7), with significant heterogeneity (p < 0.10; I2 = 100%; tau2 = 2.13) largely explained by the different DDI identification methods. Therefore, 26 studies were qualitatively synthesised and seven studies were eligible for separate meta-analyses. In a meta-analysis of three studies (N = 1122) using Micromedex®, pooled DDI prevalence was 57.8% (95% CI 52.2–63.2; I2 = 69.6%, p < 0.01). In a meta-analysis of two studies (N = 809,113) using Lexi-Interact®, pooled DDI prevalence was 30.3% (95% CI 30.2–30.4; I2 = 6.8%). In a meta-analysis of two studies (N = 947) using the 2015 American Geriatrics Society Beers criteria®, pooled DDI prevalence was 16.6% (95% CI 5.6–40.2; I2 = 97.5%, p < 0.01). Common DDIs frequently involved cardiovascular drugs, including ACE inhibitor-potassium-sparing diuretic; amiodarone-digoxin; and amiodarone-warfarin. Conclusions: DDIs are prevalent among older community-dwelling individuals; however, the methodology used to estimate these events varies considerably. A standardised methodology is needed to allow meaningful measurement and comparison of DDI prevalence. [ABSTRACT FROM AUTHOR]

Aichi Target 11 committed governments to protect ≥17% of their terrestrial environments by 2020, yet it was rarely achieved, raising questions about the post-2020 Global Biodiversity Framework goal to protect 30% by 2030. Asia is a challenging continent for such targets, combining high biodiversity with dense human populations. Here, we evaluated achievements in Asia against Aichi Target 11. We found that Asia was the most underperforming continent globally, with just 13.2% of terrestrial protected area (PA) coverage, averaging 14.1 ± SE 1.8% per country in 2020. 73.1% of terrestrial ecoregions had <17% representation and only 7% of PAs even had an assessment of management effectiveness. We found that a higher agricultural land in 2015 was associated with lower PA coverage today. Asian countries also showed a remarkably slow average annual pace of 0.4 ± SE 0.1% increase of PA extent. These combined lines of evidence suggest that the ambitious 2030 targets are unlikely to be achieved in Asia unless the PA coverage to increase 2.4-5.9 times faster. We provided three recommendations to support Asian countries to meet their post-2020 biodiversity targets: complete reporting and the wider adoption "other effective area-based conservation measures"; restoring disturbed landscapes; and bolstering transboundary PAs. Asia is shown to be behind in meeting the Aichi Target 11 under the Convention on Biological Diversity and current trends indicate that 2030 targets are unlikely to be achieved with severe impact on biodiversity. [ABSTRACT FROM AUTHOR]

In 2018, the giant manta ray was listed as threatened under the U.S. Endangered Species Act. We integrated decades of sightings and survey effort data from multiple sources in a comprehensive species distribution modeling (SDM) framework to evaluate the distribution of giant manta rays off the eastern United States, including the Gulf of Mexico. Manta rays were most commonly detected at productive nearshore and shelf-edge upwelling zones at surface thermal frontal boundaries within a temperature range of approximately 20–30 °C. SDMs predicted highest nearshore occurrence off northeastern Florida during April, with the distribution extending northward along the shelf-edge as temperatures warm, leading to higher occurrences north of Cape Hatteras, North Carolina from June to October, and then south of Savannah, Georgia from November to March as temperatures cool. In the Gulf of Mexico, the highest nearshore occurrence was predicted around the Mississippi River delta from April to June and again from October to November. SDM predictions will allow resource managers to more effectively protect manta rays from fisheries bycatch, boat strikes, oil and gas activities, contaminants and pollutants, and other threats. [ABSTRACT FROM AUTHOR]

This correction notice is for an article titled "Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis" published in Nature Communications. The correction addresses the omission of the statement "*The authors contributed equally" from the original article. The authors of the article are listed as Maryam Ghashghaei, Yilin Liu, James Ettles, Giuseppe Bombaci, Niveditha Ramkumar, Zongmin Liu, Leo Escano, Sandra Spencer Miko, Yerin Kim, Joseph A. Waldron, Kim Do, Kyle MacPherson, Katie A. Yuen, Thilelli Taibi, Marty Yue, Aaremish Arsalan, Zhen Jin, Glenn Edin, Aly Karsan, Gregg B. Morin, Florian Kuchenbauer, Fabiana Perna, Martin Bushell, and Ly P. Vu. [Extracted from the article]

The population aging on the Autism Spectrum (AS) faces disproportionate physical and mental health comorbidities. This research describes self-care practices, including physical activity (PA), nutrition, and spirituality, and the impact of these practices on the health and well-being of older adults on the AS. Researchers conducted semi-structured interviews (N = 30) with older adults (age 50+ years) on the AS on the following topics: health, employment, relationships, and services/supports. Data were analyzed using Dedoose software and a constant comparative method. Participants described self-reported health benefits of their PA. Participants who engaged with organizations reported receiving instrumental support and fulfillment. Several themes emerged regarding socialization and routines in self-care in older adults on the AS, which may inform interventions. [ABSTRACT FROM AUTHOR]