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Background and aimsMany agricultural areas are expected to face hotter, drier conditions from climate change. Understanding the mechanisms that crops use to mitigate these stresses can guide breeding for more tolerant plant material. We tested relationships between traits, physiological function in hot conditions and historical climate associations to evaluate these mechanisms for winegrapes. We expected a more negative leaf osmotic potential at full hydration (πo), which reduces leaf turgor loss during drought, and either a metabolically cheaper or more osmoprotectant leaf chemical composition, to allow cultivars associated with hot, dry regions to maintain greater gas exchange in hot growing conditions.MethodsWe measured πo, gas exchange and leaf chemistry for seven commercially important winegrape cultivars that vary widely in historical climate associations. Vines were grown in common-garden field conditions in a hot wine-growing region (Davis, CA, USA) and measured over the hottest period of the growing season (July-September).Key resultsThe value of πo varied significantly between cultivars, and all cultivars significantly reduced πo (osmotically adjusted) over the study period, although osmotic adjustment did not vary across cultivars. The value of πo was correlated with gas exchange and climate associations, but in the direction opposite to expected. Photosynthesis and πo were higher in the cultivars associated with hotter, less humid regions. Leaf chemical composition varied between cultivars but was not related to climate associations.ConclusionsThese findings suggest that maintenance of leaf turgor is not a primary limitation on grapevine adaptation to hot or atmospherically dry growing conditions. Thus, selecting for a more negative πo or greater osmotic adjustment is not a promising strategy to develop more climate-resilient grape varieties, contrary to findings for other crops. Future work is needed to identify the mechanisms increasing photosynthesis in the cultivars associated with hot, dry regions.

Background The importance of gut microbes in mediating the benefits of lifestyle intervention is increasingly recognized. However, compared to the bacterial microbiome, the role of intestinal fungi in exercise remains elusive. With our established randomized controlled trial of exercise intervention in Chinese males with prediabetes (n = 39, ClinicalTrials.gov:NCT03240978), we investigated the dynamics of human gut mycobiome and further interrogated their associations with exercise-elicited outcomes using multi-omics approaches.Methods Clinical variations and biological samples were collected before and after training. Fecal fungal composition was analyzed using the internal transcribed spacer 2 (ITS2) sequencing and integrated with paired shotgun metagenomics, untargeted metabolomics, and Olink proteomics.Results Twelve weeks of exercise training profoundly promoted fungal ecological diversity and intrakingdom connection. We further identified exercise-responsive genera with potential metabolic benefits, including Verticillium, Sarocladium, and Ceratocystis. Using multi-omics approaches, we elucidated comprehensive associations between changes in gut mycobiome and exercise-shaped metabolic phenotypes, bacterial microbiome, and circulating metabolomics and proteomics profiles. Furthermore, a machine-learning algorithm built using baseline microbial signatures and clinical characteristics predicted exercise responsiveness in improvements of insulin sensitivity, with an area under the receiver operating characteristic (AUROC) of 0.91 (95% CI: 0.85–0.97) in the discovery cohort and of 0.79 (95% CI: 0.74–0.86) in the independent validation cohort (n = 30).Conclusions Our findings suggest that intense exercise training significantly remodels the human fungal microbiome composition. Changes in gut fungal composition are associated with the metabolic benefits of exercise, indicating gut mycobiome is a possible molecular transducer of exercise. Moreover, baseline gut fungal signatures predict exercise responsiveness for diabetes prevention, highlighting that targeting the gut mycobiome emerges as a prospective strategy in tailoring personalized training for diabetes prevention.

Cortical thickness changes dramatically during development and is associated with adolescent drinking. However, previous findings have been inconsistent and limited by region-of-interest approaches that are underpowered because they do not conform to the underlying spatially heterogeneous effects of alcohol. In this study, adolescents (n = 657; 12-22 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study who endorsed little to no alcohol use at baseline were assessed with structural magnetic resonance imaging and followed longitudinally at four yearly intervals. Seven unique spatial patterns of covarying cortical thickness were obtained from the baseline scans by applying an unsupervised machine learning method called non-negative matrix factorization (NMF). The cortical thickness maps of all participants' longitudinal scans were projected onto vertex-level cortical patterns to obtain participant-specific coefficients for each pattern. Linear mixed-effects models were fit to each pattern to investigate longitudinal effects of alcohol consumption on cortical thickness. We found in six NMF-derived cortical thickness patterns, the longitudinal rate of decline in no/low drinkers was similar for all age cohorts. Among moderate drinkers the decline was faster in the younger adolescent cohort and slower in the older cohort. Among heavy drinkers the decline was fastest in the younger cohort and slowest in the older cohort. The findings suggested that unsupervised machine learning successfully delineated spatially coordinated patterns of vertex-level cortical thickness variation that are unconstrained by neuroanatomical features. Age-appropriate cortical thinning is more rapid in younger adolescent drinkers and slower in older adolescent drinkers, an effect that is strongest among heavy drinkers.

Abstract Increasing attention has been drawn to the misuse of statistical methods over recent years, with particular concern about the prevalence of practices such as poor experimental design, cherry picking and inadequate reporting. These failures are largely unintentional and no more common in ecology than in other scientific disciplines, with many of them easily remedied given the right guidance. Originating from a discussion at the 2020 International Statistical Ecology Conference, we show how ecologists can build their research following four guiding principles for impactful statistical research practices: (1) define a focussed research question, then plan sampling and analysis to answer it; (2) develop a model that accounts for the distribution and dependence of your data; (3) emphasise effect sizes to replace statistical significance with ecological relevance; and (4) report your methods and findings in sufficient detail so that your research is valid and reproducible. These principles provide a framework for experimental design and reporting that guards against unsound practices. Starting with a well‐defined research question allows researchers to create an efficient study to answer it, and guards against poor research practices that lead to poor estimation of the direction, magnitude, and uncertainty of ecological relationships, and to poor replicability. Correct and appropriate statistical models give sound conclusions. Good reporting practices and a focus on ecological relevance make results impactful and replicable. Illustrated with two examples—an experiment to study the impact of disturbance on upland wetlands, and an observational study on blue tit colouring—this paper explains the rationale for the selection and use of effective statistical practices and provides practical guidance for ecologists seeking to improve their use of statistical methods.

Muscadinia rotundifolia cv. Trayshed is a valuable source of resistance to grape powdery mildew. It carries 2 powdery mildew resistance-associated genetic loci, Run1.2 on chromosome 12 and Run2.2 on chromosome 18. The purpose of this study was to identify candidate resistance genes associated with each haplotype of the 2 loci. Both haplotypes of each resistance-associated locus were identified, phased, and reconstructed. Haplotype phasing allowed the identification of several structural variation events between haplotypes of both loci. Combined with a manual refinement of the gene models, we found that the heterozygous structural variants affected the gene content, with some resulting in duplicated or hemizygous nucleotide-binding leucine-rich repeat genes. Heterozygous structural variations were also found to impact the domain composition of some nucleotide-binding leucine-rich repeat proteins. By comparing the nucleotide-binding leucine-rich repeat proteins at Run1.2 and Run2.2 loci, we discovered that the 2 loci include different numbers and classes of nucleotide-binding leucine-rich repeat genes. To identify powdery mildew resistance-associated genes, we performed a gene expression profiling of the nucleotide-binding leucine-rich repeat genes at Run1.2b and Run2.2 loci with or without powdery mildew present. Several nucleotide-binding leucine-rich repeat genes were constitutively expressed, suggesting a role in powdery mildew resistance. These first complete, haplotype-resolved resistance-associated loci and the candidate nucleotide-binding leucine-rich repeat genes identified by this study are new resources that can aid the development of powdery mildew-resistant grape cultivars.

In The Sources of Religious Insight, Josiah Royce assesses William James’ pragmatic evaluation of exalted, private religious experience, advanced in The Varieties of Religious Experience as inadequate to encompass the full range of religious experience. Among other contributions, Royce adds social and communal experience to James’ individualistic appraisal. Rather than tacking on to the familiar contemporary critical conversation about the Jamesian restriction to private experience, I argue that James and Royce are helpfully brought together through an understanding of religious conversion: James’ foundational predicament of the “sick soul” returned to health through religious conversion gains depth and coherence through the attention Royce gives to overcoming alienation through communal participation. In our time of dislocation and self-preoccupation, drawing together these two seminal models of religious experience provides an instructive account of the individual’s transformation by way of communal renewal.

Introduction: Acute presentation of multiple myeloma in the emergency department (ED) is an uncommon yet life-threatening clinical entity.Case Report: A 42-year-old male presented to the ED with severe generalized fatigue and vision changes most notable in his left eye. Bilateral central retinal vein occlusion (CRVO) was diagnosed on dilated fundus exam in the ED.Conclusion: The most common cause of CRVO in adults over age 50 is vascular disease, but in younger adults, conditions of systemic inflammation or hyperviscosity must be considered. Diagnosis of CRVO requires emergent ophthalmology consultation and further treatment with phototherapy, steroids, and potentially anti-vascular endothelial growth factor. Ultimately, patients require hematology/oncology and ongoing management of acute hyperviscosity syndrome. We present this case to increase awareness surrounding this diagnosis among emergency physicians. Multiple myeloma should be considered in young patients who present to the ED with bilateral CRVO, acute renal failure, and symptomatic anemia.

Climate change's particular ‘perfect storm’ problem-nature requires educators and communicators to acknowledge that a single ‘silver bullet’ intervention that eliminates ignorance and denial regarding global warming may never emerge. However, diverse kinds of information-hunks and educational initiatives do incrementally increase acceptance (and alarm) regarding climate change, thus decreasing ignorance/denial. We herein describe advances in several climate education realms, including in-school and extra-school youth learning––along with post-school, general public, climate change communications. Our review includes lenses on socio-emotional learning, social justice, and techniques for addressing misinformation. Finally, we describe a particular set of ten hunks of experimentally vetted information, generally taking less than five minutes, that our laboratory has shown effective in boosting acceptance that global warming is occurring and concerning.

Abstract Background Atrioventricular septal defects (AVSD) represent 4–7% of congenital cardiac malformations. Definitive early repair is favored over prior pulmonary artery banding and delayed definitive repair in many centers. The aim of this study was to analyze long-term outcomes following AVSD repair over a 21-year period. Methods A total of 202 consecutive patients underwent surgical AVSD correction between June 1999 and December 2020. Surgery was performed using the double-patch technique. The study data were prospectively collected and retrospectively analyzed. Primary outcomes were In-hospital mortality and overall long-term freedom from reoperation. Results Median age at operation was 120 days (IQR 94–150), median weight was 5.0 kg (4.2–5.3). None of the patients died within the first 30 postoperative days. In-hospital mortality was 0.5% (1/202 patients). Median follow-up was 57 months (11–121). Overall freedom from reoperation at 5, 10 and 15 years was 91.8%, 86.9% and 86.9%, respectively. Conclusion AVSD repair with the double-patch technique is a safe and effective procedure with good early postoperative outcomes and low long-term reoperation rates.

Abstract Background The guidelines for mechanical circulatory support of the International Society for Heart and Lung Transplantation do not recommend the routine replacement or repair of the mitral valve at the time point of left ventricular assist device (LVAD) implantation. We investigated different parameters of health status including exercise capacity, anxiety and depression after LVAD implantation in patients with different preoperative grades of mitral regurgitation (MR). Methods A single-center analysis of health status was performed including 45 patients with HeartMate 3 (HM 3) implantation using the 12-items Short Form Health Survey (SF-12) and the Hospital Anxiety and Depression Score (HADS) questionnaires. The study groups were classified according to echocardiographically defined preoperative grade of MR. The group without severe MR comprised 33 patients; the group with severe MR comprised 12 patients. Results Demographic and preclinical characteristics as well as LVAD complications such as thrombosis and bleeding events were comparable between LVAD patients with severe and not severe MR (p > 0.05). Severe MR resolved in all patients after LVAD implantation and improved to moderate, mild or no MR in both groups in a period ranging from 6 months until 2 years. The analyses of SF-12 questionnaire revealed that the physical (p = 0.44) and mental health (p = 0.64) was comparable. The grade of anxiety (p = 0.34) and depression (p = 0.44) was comparable between the groups. Exercise capacity measured by the 6 min walk test correlated positively with the SF-12-determined physical health (p

While repetitive transcranial magnetic stimulation (rTMS) is widely used to treat psychiatric disorders, innovations are needed to improve its efficacy. An important limitation is that while psychiatric disorders are associated with fronto-limbic dysregulation, rTMS does not have sufficient depth penetration to modulate affected subcortical structures. Recent advances in task-related functional connectivity provide a means to better link superficial and deeper cortical sources with the possibility of increasing fronto-limbic modulation to induce stronger therapeutic effects. The objective of this pilot study was to test whether task-related, connectivity-based rTMS could modulate amygdala activation through its connectivity with the medial prefrontal cortex (mPFC). fMRI was collected to identify a node in the mPFC showing the strongest connectivity with the amygdala, as defined by psychophysiological interaction analysis. To promote Hebbian-like plasticity, and potentially stronger modulation, 5 Hz rTMS was applied while participants viewed frightening video-clips that engaged the fronto-limbic network. Significant increases in both the mPFC and amygdala were found for active rTMS compared to sham, offering promising preliminary evidence that functional connectivity-based targeting may provide a useful approach to treat network dysregulation. Further research is needed to better understand connectivity influences on rTMS effects to leverage this information to improve therapeutic applications.

The increase of misinformation in the public sphere over thepast decade represents an urgent societal issue, given thechallenge of distinguishing veridical facts from false ormisleading information. The present experiment’s resultsindicate that people are reliant on numerical information in theirdetermination of whether a statistic related to global warming isrepresentative or misleading. Of particularly practicalsignificance, the results also demonstrate that showingparticipants a mixed set of revealing and misleading globalwarming statistics leads to an increase in global warmingacceptance, rather than sowing confusion (or some sense that alldata are equally dubious or compelling). Replicating priorresults, nationalism and global warming acceptance are in anegative relationship. We also describe the background, design,and assessment of a curriculum intended to help the generalpublic better distinguish between representative and misleadingstatistics about anthropogenic climate change. The findingshighlight numerically-driven inferencing as a useful paradigmfor the assessment of information relating to global warming andenvironmental risk.

Cognitive impediments and global warming's gradual pace, among other factors, have inhibited some people from detecting climate change's everyday effects. This results in global warming often being perceived as a non-urgent, non-personal, threat that inhibits larger-scale collective action combatting climate change and public will regarding such action. Extreme weather events that global warming causes or exacerbates (e.g., hurricanes, flooding, heat, and droughts), however, are memorable due to their high emotional, social, and economic costs. Sea level rise is an especially salient American issue, given recent heightened storm surges, and the large population-segment who live in or near coastal areas with dangerous flooding risks. In this experiment, we show that providing American participants with U.S.-specific information about the economic and/or geographic/cartological effects and risks of sea level rise results in (a) an increased acceptance of oceanic rise as a phenomenon that is concerning and caused by global warming, and (b) an increased acceptance, in general, of global warming's anthropogenic nature. Communicating sea level rise information also led to (c) a general decrease in nationalism and (d) changes in the perceived effectiveness of mitigation strategies for sea level rise–specifically (d1) a decrease in the perceived effectiveness of constructing sea walls /dikes and (d2) an increase in the perceived effectiveness of phasing out fossil fuel usage. Overall, we find that communicating striking information about this oceanic by-product of global warming is an effective way to motivate acceptance and engagement with the issue of climate change in a reasonably broad manner. The experimental findings replicate, extend, and dovetail with prior experiments by our laboratory, bringing up to six the number of brief interventions (i.e., of roughly 5 or fewer minutes) that have been proven to increase people's science-normative beliefs about global warming. Our laboratory's website, HowGlobalWarmingWorks.org, offers samples of these materials, which additionally include surprising statistics, textual and video explanations of global warming's mechanism, and a contrast of Earth's temperature rise since the 1880's vs. the U.S. stock market rise since then.

It is clear that alcohol consumption is a major risk factor in the pathogenesis of head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanism underlying the pathogenesis of alcohol-associated HNSCC remains poorly understood. The aim of the present study was to identify and characterize P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) and PIWI proteins dysregulated in alcohol-associated HNSCC to elucidate their function in the development of this cancer. Using next generation RNA-sequencing (RNA-seq) data obtained from 40 HNSCC patients, the piRNA and PIWI protein expression of HNSCC samples was compared between alcohol drinkers and non-drinkers. A separate piRNA expression RNA-seq analysis of 18 non-smoker HNSCC patients was also conducted. To verify piRNA expression, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed on the most differentially expressed alcohol-associated piRNAs in ethanol and acetaldehyde-treated normal oral keratinocytes. The correlation between piRNA expression and patient survival was analyzed using Kaplan-Meier estimators and multivariate Cox proportional hazard models. A comparison between alcohol drinking and non-drinking HNSCC patients demonstrated that a panel of 3,223 piRNA transcripts were consistently detected and differentially expressed. RNA-seq analysis and in vitro RT-qPCR verification revealed that 4 of these piRNAs, piR-35373, piR-266308, piR-58510 and piR-38034, were significantly dysregulated between drinking and non-drinking cohorts. Of these four piRNAs, low expression of piR-58510 and piR-35373 significantly correlated with improved patient survival. Furthermore, human PIWI-like protein 4 was consistently upregulated in ethanol and acetaldehyde-treated normal oral keratinocytes. These results demonstrate that alcohol consumption may cause dysregulation of piRNA expression in HNSCC and in vitro verifications identified 4 piRNAs that may be involved in the pathogenesis of alcohol-associated HNSCC.

Abstract Caliper and ultrasound (US) are used to measure subcutaneous fat tissue depth (SFT) and then to calculate total body fat. There is no evidence-based recommendation as to whether caliper or US are equally accurate. The aim of this paper was therefore to compare reliability of both methods. In this methodical study, 54 participants (BMI: 24.8 ± 3.5 kg/m2; Age: 43.2 ± 21.7 years) were included. Using systematic body mapping, the SFT of 56 areas was measured. We also analyzed 4 body sites via MRI. A comparison between caliper and US detected clear differences in mean SFT of all areas (0.83 ± 0.33 cm vs. 1.14 ± 0.54 cm; p

Background No data currently exist comparing the contemporary iterations of balloon‐expandable (BE) Edwards SAPIEN 3/Ultra and the self‐expanding (SE) Medtronic Evolut PRO/R34 valves. The aim of the study was the comparison of these transcatheter heart valves with emphasis on patients with small aortic annulus. Methods and Results In this retrospective registry, periprocedural outcomes and midterm all‐cause mortality were analyzed. A total of 1673 patients (917 SE versus 756 BE) were followed up for a median of 15 months. A total of 194 patients died (11.6%) during follow‐up. SE and BE groups showed similar survival at 1 (92.6% versus 90.6%) and 3 (80.3% versus 85.2%) years (Plog‐rank=0.136). Compared with the BE group, patients treated with the SE device had lower peak (16.3±8 mm Hg SE versus 21.9±8 mm Hg BE) and mean (8.8±5 mm Hg SE versus 11.5±5 mm Hg BE) gradients at discharge. Conversely, the BE group demonstrated lower rates of at least moderate paravalvular regurgitation postoperatively (5.6% versus 0.7% for SE and BE valves, respectively; P

Mechanism driving continental growth on modern Earth has long been debated. By interpreting the long deep seismic reflection data across the ongoing India-Eurasia collision zone, the authors report crustal-scale magma accretion onto the south of central Lhasa terrane produced net continental growth.

Objective: Rare disease Background: Streptococcus pneumoniae is an uncommon but serious cause of infective endocarditis (IE), particularly in immunocompromised individuals, such as those with untreated HIV. When pneumococcal IE occurs, it is associated with high morbidity and mortality due to the high prevenance of complications such as acute valvular destruction and septic embolization. Therefore, early recognition and prompt surgical intervention are paramount to improving outcomes. This case report highlights the complexity of diagnosing and managing pneumococcal IE in the context of concurrent infections and immunosuppression. Case Report: We present a rare case of a 37-year-old man with untreated HIV who presented with fever, confusion, and back pain. He had a history of pneumococcal sepsis and meningitis a year prior. This time, he was diagnosed with pneumococcal sepsis, meningitis, and mitral valve infective endocarditis with large vegetations, which triggered the prompt involvement of a multidisciplinary treatment team for further operative management in addition to the indicated antimicrobial therapy. The case was concluded with successful operative mitral valve replacement. Conclusions: Pneumococcal infective endocarditis is an uncommon but potentially fatal complication of pneumococcal bacteremia. In patients with risk factors such as untreated HIV, a high degree of clinical suspicion is required to ensure early diagnosis. Timely surgical intervention, along with targeted antimicrobial therapy, are critical to improving outcomes in these patients. Multidisciplinary collaboration is essential to prevent further complications, making early operative management a key element in the successful treatment of pneumococcal IE. Improving vaccination efforts in vulnerable populations could reduce the incidence of such severe cases. [ABSTRACT FROM AUTHOR]

Background: Since the emergence of the pandemic, healthcare workers have been subjected to devastating psychological burden at all levels of healthcare. Depression, anxiety, and stress were greatly encountered in the era of the pandemic. Moreover, healthcare workers reported escalating levels of burnout syndrome compared to levels reported in the pre-pandemic era. They are exposed to multiple work-related stressors that have been exhausting to their mental and psychological well-being. The aim of the current study was to assess the impact of COVID-19 pandemic on the psychological well-being of healthcare workers. Methods: A comparative cross-sectional study was conducted among 471 healthcare workers (245 front-line and 226 second-line healthcare workers) recruited from ten governmental hospitals. Data was collected using self-administered structured questionnaire, Depression, Anxiety and Stress Scale-21 Items (DASS-21) and Copenhagen Burnout Inventory (CBI). Results: Symptoms suggestive of depression, anxiety, and stress were reported by 72.6%, 31.4%, and 18.6% of studied healthcare workers, respectively. Front-line healthcare workers had significantly higher mean anxiety and stress scores compared to second-line ones. Burnout syndrome was reported by 86.4% of the study subjects, with statistically significant differences between front-line and second-line healthcare workers. The most commonly adopted organizational interventions against work-related stressors were increased workforce (41.6%), frequent staff meetings (32.3%), shifts rescheduling (31.4%), frequent breaks during the working day (29.1%), and staff training (16.8%). As for individually adopted interventions, following strict protective measures (63.5%), gaining more knowledge about COVID-19 (54.1%), avoiding media news (44.8%), and relaxation activities such as prayers, music, and meditation (37.2%) were the most commonly adopted interventions. [ABSTRACT FROM AUTHOR]