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•Largest and most diverse genetic study of plasma fibrinogen identifies 54 regions (18 novel), housing 69 distinct variants (20 novel).•Links to (1) liver enzyme, blood cell, and lipid genetic signals, (2) liver regulatory elements, and (3) thrombotic and inflammatory disease.

Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases.

BACKGROUND:Parsonage-Turner syndrome (PTS) is a rare brachial neuritis of sudden onset resulting in constant, severe shoulder girdle pain followed by weakness and sensory deficits. The complex presentation often results in delayed diagnosis or misdiagnosis. This case report provides insight into a comprehensive approach to diagnosing PTS.CASE PRESENTATION:A 50-year-old man began experiencing severe left shoulder pain 48 hours before seeking medical treatment.OUTCOME AND FOLLOW-UP:The lack of conclusive findings during the physical therapy evaluation prompted a magnetic resonance imaging that revealed PTS. The patient reported full resolution of symptoms within 12 months.DISCUSSION:Severe pain, neurological weakness, and sensory changes led to the initial suspicion of a rotator cuff tear and brachial plexus injury, and a magnetic resonance imaging was recommended. This case study adds to the body of evidence emphasizing the importance of differential diagnosis in patients with neuromusculoskeletal involvement. JOSPT Cases 2024;4(4):176-179. Epub 18 September 2024. doi:10.2519/josptcases.2024.0038

Background:Traditionally, surgical repair of phalanx fractures was performed under general anesthesia. However, the emergence of regional and local anesthesia, otherwise known as Wide-awake Local Anesthesia No Tourniquet, provides an alternative approach where general anesthesia is undesirable. The choice of anesthetic approach resides with clinicians, though it is important to factor in the evidence that regional/local provides not only an alternative anesthesia approach but also potentially avoids comorbidities associated with general anesthesia. This study hypothesizes that the use of local/regional anesthesia for phalanx fracture/dislocation has comparable outcomes to general anesthesia and provides for fewer adverse events. Methods:To answer the research purpose, the investigators designed and implemented a retrospective cohort study of consecutive cases reported to the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database between January 1, 2015, and December 31, 2019. The study population included patients in the NSQIP database who underwent operative fixation of a phalanx fracture or dislocation in 2 cohorts, those with local/regional anesthesia or general anesthesia. The predictor variables were preoperative patient demographic data, including age, gender, surgical specialty, elective surgery, diabetes, smoking, hypertension, and open wound. Results:A total of 2831 patients were identified in the NSQIP database between January 1, 2015, and December 31, 2019. Local/regional anesthesia was performed in 13% of patients with the remaining 87% receiving general anesthesia. Surgical site occurrences were not clinically significant between the 2 groups. Overall, 30-day post-operative complications in the local/regional cohort included one patient with a deep vein thrombosis (0.03%) and pulmonary embolus (0.02%). Overall, 30-day post-operative complications in the general anesthesia cohort included pneumonia (0.12%) and stroke (0.08%). Conclusions:Surgery using the regional/local anesthesia techniques for patients with phalanx fractures or dislocations is safe and can be used in situations where general anesthesia is undesirable as post-operative 30-day complications are similar to those with general anesthesia.

Hypertension impacts most older adults as one of many multiple chronic conditions. A thorough evaluation is required to assess overall health, cardiovascular status, and comorbid conditions that impact treatment targets. In the absence of severe frailty or dementia, intensive treatment prevents more cardiovascular events than standard treatment and may slow cognitive decline. “Start low and go slow” is not the best strategy for many older adults as fewer cardiovascular events occur when hypertension is controlled within the first 3 to 6 months of treatment.

English Abstract:The staff of the Anne Potter Wilson Library at Vanderbilt University has faced the challenge of providing digital scores to our users since 2016. This article describes procedures developed for acquiring, cataloguing, storing, seeking out usage permissions, and making accessible digital scores. Our collections of scores, whether print or electronic, have traditionally focused on contemporary works and more recently, scores of underrepresented composers. The only way to be responsive to the needs of our users in the Blair School of Music at Vanderbilt University has been to establish a workflow for purchasing self-published scores for our collections, often only available in digital format. It takes more time and effort to locate, purchase, seek out appropriate licensing permissions, and make accessible digital scores, but if we, as music information professionals, are to continue our efforts in advocating for new music and encouraging our users to explore the repertoire of diverse composers, then we must find solutions in our libraries. This article is a description of our digital scores acquisition and cataloguing workflow, and how it has evolved over a seven-year period. Alma Digital, a hosting and access tool for digital files, is described as one way a library can provide access to digital scores.French Abstract:Le personnel de la bibliothèque Anne Potter Wilson de l’Université Vanderbilt a relevé le défi de proposer des partitions numériques à ses usagers depuis 2016. Cet article décrit les procédures mises en place pour l’acquisition, le catalogage, le stockage, l’obtention des autorisations d’utilisation et la mise à disposition des partitions numériques. Nos collections de partitions, qu’elles soient imprimées ou électroniques, se sont traditionnellement concentrées sur les œuvres contemporaines et, plus récemment, sur les partitions de compositeurs sous-représentés. La seule façon de répondre aux besoins des utilisateurs de la Blair School of Music de l’université Vanderbilt a été d’établir un flux de travail permettant d’acquérir des partitions auto-publiées pour nos collections, souvent disponibles uniquement en format numérique. Il faut plus de temps et d’efforts pour localiser, acheter, rechercher les autorisations de licence appropriées et rendre accessibles les partitions numériques. Mais si nous, en tant que professionnels de l’information musicale, voulons poursuivre nos efforts pour promouvoir la musique nouvelle et encourager nos utilisateurs à explorer le répertoire de compositeurs les plus divers, nous devons trouver les solutions au sein de nos bibliothèques. Cet article décrit notre processus d’acquisition et de catalogage des partitions numériques et comment il a évolué sur une période de sept ans. Alma Digital, un outil d’hébergement et d’accès aux fichiers numériques, est présenté comme un exemple de la manière dont une bibliothèque peut fournir un accès aux partitions numériques.German Abstract:Die Mitarbeiter der Anne Potter Wilson Library an der Vanderbilt University stehen seit 2016 vor der Herausforderung, ihren Benutzern digitale Notenausgaben zur Verfügung zu stellen. Dieser Artikel beschreibt die Verfahren, die für den Erwerb, die Katalogisierung, die Speicherung, die Einholung von Nutzungsberechtigungen und die Bereitstellung digitaler Noten entwickelt wurden. Unsere Notenbestände – ob gedruckt oder elektronisch – konzentrieren sich traditionell auf zeitgenössische Werke und in jüngerer Zeit auf Werke unterrepräsentierter Komponistinnen und Komponisten. Die einzige Möglichkeit, auf die Bedürfnisse unserer Benutzer von der Blair School of Music an der Vanderbilt University einzugehen, besteht darin, einen Workflow für den Erwerb von Eigenveröffentlichungen einzurichten, die oft nur in digitalem Format verfügbar sind. Recherche, Erwerbung, Einholen geeigneter Lizenzberechtigungen und die Bereitstellung digitaler Noten erfordern mehr Zeit und Aufwand. Aber wenn wir als Fachleute für Musikinformation unser Bestreben fortsetzen wollen, für Neue Musik einzutreten und unsere Benutzer zu ermutigen, das Repertoire verschiedenster Komponistinnen und Komponisten zu erkunden, müssen wir Lösungen in unseren Bibliotheken finden. Dieser Artikel beschreibt unseren Workflow für Erwerbung und Katalogisierung digitaler Notenausgaben sowie dessen Entwicklung innerhalb eines Zeitraums von sieben Jahren. Alma Digital, ein Hosting- und Zugriffstool für digitale Dateien, wird als eine Möglichkeit beschrieben, wie eine Bibliothek Zugriff auf digitale Noten ermöglichen kann.

The impact of socioeconomic distress on readmission rates following cardiac surgery has not been studied. We hypothesized that patients living in distressed communities would have a higher 30-day readmission rate after cardiac surgery compared to those living in less distressed communities.

Circulating tumor DNA (ctDNA) status before cystectomy can be used as a prognostic marker for disease recurrence and can predict lymph node involvement and locally advanced disease. Incorporation of ctDNA into clinical practice could help in guiding treatment intensification or deintensification.

At the first interim analysis of the KEYNOTE-671 trial, adding perioperative pembrolizumab to neoadjuvant chemotherapy significantly improved event-free survival in participants with early-stage non-small-cell lung cancer (NSCLC). We report overall survival and health-related quality of life outcomes from the second interim analysis.

Cells contain intricate protein nanostructures, but replicating them outside of cells presents challenges. One such example is the vertical fibronectin pillars observed in embryos. Here, we demonstrate the creation of cell-free vertical fibronectin pillar mimics using nonequilibrium self-assembly. Our approach utilizes enzyme-responsive phosphopeptides that assemble into nanotubes. Enzyme action triggers shape changes in peptide assemblies, driving the vertical growth of protein nanopillars into bundles. These bundles, with peptide nanotubes serving as a template to remodel fibronectin, can then recruit collagen, which forms aggregates or bundles depending on their types. Nanopillar formation relies on enzyme-catalyzed nonequilibrium self-assembly and is governed by the concentrations of enzyme, protein, peptide, the structure of the peptide, and peptide assembly morphologies. Cryo-EM reveals unexpected nanotube thinning and packing after dephosphorylation, indicating a complex sculpting process during assembly. Our study demonstrates a cell-free method for constructing intricate, multiprotein nanostructures with directionality and composition.

Epidemiologic evidence has emerged showing an association between exposure to air pollution and increased risks of gestational diabetes mellitus (GDM). This study examines the effect of low-level air pollution exposure on a subclinical biomarker of hyperglycemia (i.e., HbA1c) in pregnant people without diabetes before conception. We measured HbA1c in 577 samples repeatedly collected from 224 pregnant people in Rochester, NY, and estimated residential concentrations of PM2.5and NO2using high-resolution spatiotemporal models. We observed a U-shaped trajectory of HbA1c during pregnancy with average HbA1c levels of 5.13 (±0.52), 4.97 (±0.54), and 5.43 (±0.40)% in early-, mid-, and late pregnancy, respectively. After adjustment for the U-shaped trajectory and classic GDM risk factors, each interquartile range increase in 10 week NO2concentration (8.0 ppb) was associated with 0.09% (95% CI: 0.02 to 0.16%) and 0.18% (95% CI: 0.08 to 0.28%) increases in HbA1c over the entire pregnancy and in late pregnancy, respectively. These associations remained robust among participants without GDM. Using separate distributed lag models, we identified a period between 8th and 14th gestational weeks as critical windows responsible for increased levels of HbA1c measured at 14th, 22nd, and 30th gestational weeks. Our results suggest that low-level air pollution contributes to hyperglycemia in medically low-risk pregnant people.

Sandy Ran Xu, born around 1977, became the CEO of JD.com in May 2023, a significant Chinese e-commerce company often compared to Amazon. Xu's promotion to CEO highlighted gender diversity in top management positions in China. With a background in auditing and finance, Xu's leadership at JD.com led to impressive financial results and company growth. Her rise to CEO followed a successful tenure as CFO and marked a significant milestone for women in corporate leadership in China. [Extracted from the article]

Mark Welsh, an education administrator, became the twenty-seventh president of Texas A&M University in 2023 amidst controversy, including student protests and opposition to diversity initiatives. Welsh, a military veteran, focused on student issues and had a distinguished career in the Air Force, including serving as chief of staff. He later transitioned to academia, becoming the dean of the Bush School of Government and Public Service before assuming the presidency of Texas A&M. [Extracted from the article]

Arthur Mensch, a French scientist and entrepreneur, is the CEO of Mistral, a startup focused on artificial intelligence (AI) technology. Mistral aims to challenge American tech giants in developing large language models and democratize AI through open-source code. Mensch's background includes a PhD in machine learning and work at DeepMind before founding Mistral, which quickly gained significant investment and partnerships with major companies like Microsoft. His vision for Mistral is to create a European AI champion and promote innovation in the field. [Extracted from the article]

Jerod Mayo, the youngest active head coach in the NFL at thirty-seven, made history as the first Black head coach in Patriots history. Mayo, a former player and assistant coach for the Patriots, succeeded Bill Belichick, facing the challenge of reviving the team's playoff performance. Mayo's coaching style differed from Belichick's, focusing on a lighter and more congenial atmosphere, while emphasizing a forward-thinking approach. [Extracted from the article]

Glaciers archive time-structured information on climates and ecosystems, including microorganisms. However, the long-term ecogenomic dynamics or biogeography of the preserved viruses and their palaeoclimatic connections remain uninvestigated. Here we use metagenomes to reconstruct viral genomes from nine time horizons, spanning three cold-to-warm cycles over the past >41,000 years, preserved in an ice core from Guliya Glacier, Tibetan Plateau. We recover genomes of 1,705 approximately species-level viral operational taxonomic units. Viral communities significantly differ during cold and warm climatic conditions, with the most distinct community observed ~11,500 years ago during the major climate transition from the Last Glacial Stage to the Holocene. In silico analyses of virus–host interactions reveal persistently high viral pressure on Flavobacterium(a common dominant glacier lineage) and historical enrichment in the metabolism of cofactors and vitamins that can contribute to host adaptation and virus fitness under extreme conditions. Biogeographic analyses show that approximately one-fourth of Guliya viral operational taxonomic units overlap with the global dataset, primarily with the Tibetan Plateau metagenomes, suggesting regional associations of a subset of the Guliya-preserved viruses over time. We posit that the cold-to-warm variations in viral communities might be attributed to distinct virus sources and/or environmental selections under different temperature regimes.

The effects of long-term climate warming on soil respiration and its drivers remain unclear in forests, which store approximately 40% of global soil carbon. Here we conducted a climate change experiment for 13 years in forest plots planted with tree juveniles at two southern boreal forest sites. Treatments included simultaneous above- and below-ground warming (ambient, +1.7 °C and +3.3 °C) under different rainfall scenarios (100% and 60% of summer rainfall) and contrasting overstory canopy openness (open and closed). Soil respiration increased by 7% and 17% under +1.7 °C and +3.3 °C warming, respectively, averaged across all sites, treatments and years. These increases in respiration were higher than impacts per degree warming of the only two prior long-term, but soil-only, forest warming experiments. Moreover, warming effects on soil respiration varied significantly over time. Under almost all conditions, moist soil exhibited a greater increase in respiration in response to warming than dry soil. Our results suggest that a realistic range of anticipated conditions, including both above- and below-ground temperature and moisture, should be accounted for when predicting warming effects on soil respiration.

The Resilience Builder Program® (RBP) is a cognitive-behavioral based group therapy for children with psychosocial deficits. Previous studies in children with varied diagnoses (attention deficit/hyperactivity disorder, anxiety disorders, and autism spectrum disorders) have provided evidence for its effectiveness in emotion regulation, positive emotions, social skills, and resilience. However, little is known about the mechanisms through which specific therapeutic components of the RBP may reduce internalizing problems in children. The current study examined pre- to post-therapy change in self-regulation, resilience, and internalizing problems, and investigated the therapeutic pathways of the RBP for reducing children’s internalizing problems by accounting for resilience improvement. Children (N= 244) between 7 to 15 years old with diverse diagnoses and heterogeneous symptoms who completed the RBP were assessed with parent-report measures of executive functioning, emotion regulation, resilience, and internalizing problems prior to and following the RBP. Results found that improvement in self-regulation and resilience predicted significant reductions in internalizing problems in children following the RBP. In addition, the change in resilience was found to be a significant predictor of the relationship between the change in self-regulation and internalizing problems. These findings clarify the therapeutic mechanisms of RBP, and more broadly speak to the value of targeting self-regulation and resilience as a means of reducing internalizing problems in youth receiving psychotherapeutic interventions.

AbstractSix species of monotremes, three newly described here, occur in the Cenomanian fossil fauna from Lightning Ridge in northeastern New South Wales, Australia, making it the most diverse monotreme assemblage on record. Four species are known from a single specimen, suggesting that diversity remains underrepresented. No other mammal lineages are known from the deposit, although the absence of smaller taxa is likely due to sampling biases introduced by the opal mining process. Early-Late Cretaceous monotremes thus clearly diversified in Australia during the absence of other large-bodied mammalian competitors; and subsequently occupied a wider range of ecological niches than at any other time in their evolutionary history. One new taxon described herein represents a previously unknown monotreme family that combines marked elongation and torsion of the dentary with teinolophid character states, including the retention of five molars. Another shares dental features with ornithorhynchids, while the third is a possible diminutive steropodontid and simultaneously represents the smallest-bodied post-Barremian monotreme. Additional material of Steropodon galmaniis also documented, confirming that a Meckelian groove is rudimentary or absent in this taxon, thus adding to the morphological understanding of this unusual monotreme. Lastly, we posit that the loss of teeth in ornithorhynchids may have occurred during the Pleistocene as a result of competition with aquatic hydromyin rodents dispersing to Australia from New Guinea.Timothy F. Flannery[tim.fridtjof.flannery@gmail.com]Kristofer M. Helgen[Kris.Helgen@Australian.Museum], and Matthew McCurry[Matthew.McCurry@austmus.gov.au] Australian Museum, 1 William Street Sydney, New South Wales 2000, Australia; Earth and Sustainability Research Centre, School of Biological Earth and Environmental Science, The University of New South Wales, Sydney New South Wales 2052, AustraliaThomas H. Rich[trich@museum.vic.gov.au], Museums Victoria, PO Box 666, Melbourne, Victoria 3001, Australia; Patricia Vickers-Rich[pat.rich@monash.edu], School of Earth, Atmosphere and Environment, Monash University, Clayton, Victoria 3800, Australia; Museums Victoria, PO Box 666, Melbourne, Victoria 3001, Australia; Curtin University, Bentley Street, Perth, Western Australia 6102, AustraliaElizabeth T Smith[elizabethtsmith@exemail.com.au;contact@australianopalcentre.com] Australian Opal Centre, PO Box 229, Lightning Ridge, New South Wales 2834, Australia.

Magnesium alloys present a compelling prospect for absorbable implant materials in orthopedic and trauma surgery. This study evaluates an ultra-high purity, lean magnesium–calcium alloy (X0), both with and without plasma electrolytic oxidation (PEO) surface modification, in comparison to a clinically utilized WE43 magnesium alloy. It is shown that the mechanical properties of X0 can be tuned to yield a high-strength material suitable for bone screws (with an ultimate tensile strength of 336 MPa) or a ductile material appropriate for intraoperatively deformable plates (with an elongation at fracture of 24 %). Four plate-screw combinations were implanted onto the pelvic bones of six sheep without osteotomy for 8 weeks. Subsequent analysis utilized histology, micro-computed tomography, and light and electron microscopy. All implants exhibited signs of degradation and hydrogen-gas evolution, with PEO-coated X0 implants demonstrating the least volume loss and the most substantial new-bone formation on the implant surface and surrounding cancellous bone. Furthermore, the osteoconductive properties of the X0 implants, when uncoated, exceeded those of the uncoated WE43 implants, as evidenced by greater new-bone formation on the surface. This osteoconductivity was amplified with PEO surface modification, which mitigated gas evolution and enhanced osseointegration, encouraging bone apposition in the cancellous bone vicinity. These findings thus indicate that PEO-coated X0 implants hold substantial promise as a biocompatible and absorbable implant material.

Biodegradable magnesium is a highly desired material for fracture fixation implants because of its good mechanical properties and ability to completely dissolve in the body over time, eliminating the need for a secondary surgery to remove the implant. Despite extensive research on these materials, there remains a dearth of information regarding critical factors that affect implant performance in clinical applications, such as the in vivopH and mechanical loading conditions. We developed a measurement system with implantable strain, temperature, pH and motion sensors to characterize magnesium and titanium plates, fixating bilateral zygomatic arch osteotomies in three Swiss alpine sheep for eight weeks. pH 1–2 mm above titanium plates was 6.6 ± 0.4, while for magnesium plates it was slightly elevated to 7.4 ± 0.8. Strains on magnesium plates were higher than on titanium plates, possibly due to the lower Young's modulus of magnesium. One magnesium plate experienced excessive loading, which led to plate failure within 31 h. This is, to our knowledge, the first in vivostrain, temperature, and pH data recorded for magnesium implants used for fracture fixation. These results provide insight into magnesium degradation and its influence on the in vivoenvironment, and may help to improve material and implant design for future clinical applications.

As global change processes modify the extent and functions of terrestrial–aquatic interfaces, the variability of critical and dynamic transitional zones between wetlands and uplands increases. However, it is still unclear how fluctuating water levels at these dynamic boundaries alter groundwater biogeochemical cycling. Here, we used high-temporal resolution data along gradients from wetlands to uplands and during fluctuating water levels at freshwater coastal areas to capture spatiotemporal patterns of groundwater redox potential (Eh). We observed that topography influences groundwater Ehthat is higher in uplands than in wetlands; however, the high variability within TAI zones challenged the establishment of distinct redox zonation. Declining water levels generally decreased Eh, but most locations exhibited significant Ehvariability, which is associated with rare instances of short-term water level fluctuations, introducing oxygen. The Eh-oxygen relationship showed distinct hysteresis patterns, reflecting redox poising capacity at higher Eh, maintaining more oxidizing states longer than the dissolved oxygen presence. Surprisingly, we observed more frequent oxidizing states in transitional areas and wetlands than in uplands. We infer that occasional oxygen entering specific wetland–upland boundaries acts as critical biogeochemical control points. High-resolution data can capture such rare yet significant biogeochemical instances, supporting redox-informed models and advancing the predictability of climate change feedback.

Rob Rubba, a chef born in April 1982, gained recognition for his commitment to environmental sustainability and vegetarianism as the chef-owner of Oyster Oyster in Washington, DC. Despite his early focus on proteins, Rubba shifted towards sustainable food systems, culminating in the opening of Oyster Oyster in 2021. His innovative plant-based cuisine earned him accolades such as a Michelin Star in 2022 and the title of Outstanding Chef of 2023 by the James Beard Foundation. Rubba's personal life reflects his diverse influences, including his wife's Korean heritage, which has shaped his culinary repertoire. [Extracted from the article]

Dr. Dimie Ogoina, a physician, professor, and medical researcher, played a crucial role in identifying and researching the viral zoonotic disease mpox (formerly known as monkeypox) in Nigeria in 2017. His groundbreaking work revealed that the virus was now being transmitted through sexual contact, leading to a significant impact on global public health efforts. Despite initial skepticism, Ogoina's research was eventually recognized internationally, earning him accolades from prestigious publications and institutions. His commitment to health equity and continued research efforts have solidified his position as one of the most influential figures in the field of infectious diseases. [Extracted from the article]

IMPORTANCE: Blood pressure response during acute exercise (exercise blood pressure [EBP]) is associated with the future risk of hypertension and cardiovascular disease (CVD). Biochemical characterization of EBP could inform disease biology and identify novel biomarkers of future hypertension. OBJECTIVE: To identify protein markers associated with EBP and test their association with incident hypertension. DESIGN, SETTING, AND PARTICIPANTS: This study assayed 4977 plasma proteins in 681 healthy participants (from 763 assessed) of the Health, Risk Factors, Exercise Training and Genetics (HERITAGE; data collection from January 1993 to December 1997 and plasma proteomics from January 2019 to January 2020) Family Study at rest who underwent 2 cardiopulmonary exercise tests. Individuals were free of CVD at the time of recruitment. Individuals with resting SBP ≥160 mm Hg or DBP ≥100 mm Hg or taking antihypertensive drug therapy were excluded from the study. The association between resting plasma protein levels to both resting BP and EBP was evaluated. Proteins associated with EBP were analyzed for their association with incident hypertension in the Framingham Heart Study (FHS; n = 1177) and validated in the Jackson Heart Study (JHS; n = 772) and Multi-Ethnic Study of Atherosclerosis (MESA; n = 1367). Proteins associated with incident hypertension were tested for putative causal links in approximately 700 000 individuals using cis-protein quantitative loci mendelian randomization (cis-MR). Data were analyzed from January 2023 to January 2024. EXPOSURES: Plasma proteins. MAIN OUTCOMES AND MEASURES: EBP was defined as the BP response during a fixed workload (50 W) on a cycle ergometer. Hypertension was defined as BP ≥140/90 mm Hg or taking antihypertensive medication. RESULTS: Among the 681 participants in the HERITAGE Family Study, the mean (SD) age was 34 (13) years; 366 participants (54%) were female; 238 (35%) were self-reported Black and 443 (65%) were self-reported White. Proteomic profiling of EBP revealed 34 proteins that would not have otherwise been identified through profiling of resting BP alone. Transforming growth factor β receptor 3 (TGFBR3) and prostaglandin D2 synthase (PTGDS) had the strongest association with exercise systolic BP (SBP) and diastolic BP (DBP), respectively (TGFBR3: exercise SBP, β estimate, −3.39; 95% CI, −4.79 to −2.00; P = 2.33 × 10−6; PTGDS: exercise DBP β estimate, −2.50; 95% CI, −3.29 to −1.70; P = 1.18 × 10−9). In fully adjusted models, TGFBR3 was inversely associated with incident hypertension in FHS, JHS, and MESA (hazard ratio [HR]: FHS, 0.86; 95% CI, 0.75-0.97; P = .01; JHS, 0.87; 95% CI, 0.77-0.97; P = .02; MESA, 0.84; 95% CI, 0.71-0.98; P = .03; pooled cohort, 0.86; 95% CI, 0.79-0.92; P = 6 × 10−5). Using cis-MR, genetically predicted levels of TGFBR3 were associated with SBP, hypertension, and CVD events (SBP: β, −0.38; 95% CI, −0.64 to −0.11; P = .006; hypertension: odds ratio [OR], 0.99; 95% CI, 0.98-0.99; P < .001; heart failure with hypertension: OR, 0.86; 95% CI, 0.77-0.97; P = .01; CVD: OR, 0.84; 95% CI, 0.77-0.92; P = 8 × 10−5; cerebrovascular events: OR, 0.77; 95% CI, 0.70-0.85; P = 5 × 10−7). CONCLUSIONS AND RELEVANCE: Plasma proteomic profiling of EBP identified a novel protein, TGFBR3, which may protect against elevated BP and long-term CVD outcomes.

Pulmonary hypertension associated with left heart disease (PH-LHD) remains the most common cause of pulmonary hypertension globally. Etiologies include heart failure with reduced and preserved ejection fraction and left-sided valvular heart diseases. Despite the increasing prevalence of PH-LHD, there remains a paucity of knowledge about the hemodynamic definition, diagnosis, treatment modalities, and prognosis among clinicians. Moreover, clinical trials have produced mixed results on the usefulness of pulmonary vasodilator therapies for PH-LHD. In this expert review, we have outlined the critical role of meticulous hemodynamic evaluation and provocative testing for cases of diagnostic uncertainty. Therapeutic strategies—pharmacologic, device-based, and surgical therapies used for managing PH-LHD—are also outlined. PH-LHD in advanced heart failure, and the role of mechanical circulatory support in PH-LHD is briefly explored. An in-depth understanding of PH-LHD by all clinicians is needed for improved recognition and outcomes among patients with PH-LHD.

Precision medicine should aspire to reduce error and improve accuracy in medical and health recommendations by comparison with contemporary practice, while maintaining safety and cost-effectiveness. The etiology, clinical manifestation and prognosis of diseases such as obesity, diabetes, cardiovascular disease, kidney disease and fatty liver disease are heterogeneous. Without standardized reporting, this heterogeneity, combined with the diversity of research tools used in precision medicine studies, makes comparisons across studies and implementation of the findings challenging. Specific recommendations for reporting precision medicine research do not currently exist. The BePRECISE (Better Precision-data Reporting of Evidence from Clinical Intervention Studies & Epidemiology) consortium, comprising 23 experts in precision medicine, cardiometabolic diseases, statistics, editorial and lived experience, conducted a scoping review and participated in a modified Delphi and nominal group technique process to develop guidelines for reporting precision medicine research. The BePRECISE checklist comprises 23 items organized into 5 sections that align with typical sections of a scientific publication. A specific section about health equity serves to encourage precision medicine research to be inclusive of individuals and communities that are traditionally under-represented in clinical research and/or underserved by health systems. Adoption of BePRECISE by investigators, reviewers and editors will facilitate and accelerate equitable clinical implementation of precision medicine.

This document provides technical specifications and test results for the Porsche 911 Dakar, a high-performance off-road vehicle. The vehicle is equipped with a 473-horsepower engine, all-wheel drive, and a 8-speed dual-clutch automatic transmission. It features a raised body with increased ground clearance and stainless-steel panels for off-road protection. Test results show impressive acceleration, handling, and braking performance. The document also includes opinions from different individuals who have driven the vehicle. Competitors and dimensions are listed as well. [Extracted from the article]

Saara Kuugongelwa-Amadhila is a Namibian politician who became the country's Prime Minister in 2015, making her the youngest person and the first woman to hold that position. She has been a member of the South West Africa People's Organisation (SWAPO) and has had a long career in Namibian politics. As Prime Minister, she has represented Namibia at international events and conferences, advocating for gender equity, addressing income gaps, climate change mitigation, and policymaking for the public good. While she has faced controversy and political scandals, she has remained dedicated to her work and has received recognition for her service. [Extracted from the article]

Ryo Kiyuna, a martial artist from Okinawa, Japan, gained international attention at the 2020 Olympic Games in Tokyo when karate was included as an official Olympic event for the first time. Kiyuna, an expert in the kata format of karate, won a gold medal and touched hearts around the world by carrying a photo of his late mother on the winners' podium. He has had a successful career, winning multiple world championships and other prestigious titles. Despite karate's positive reception at the Olympics, it will not be included in the 2024 and 2028 Games. Kiyuna announced his retirement in early 2023. [Extracted from the article]

FQ Editor-at-large B. Ruby Rich starts off a year of festival-going with reports from Sundance and Berlin. At Sundance, documentary highlights included Soundtrack to a Coup d’Etat (Johan Grimonprez), about the machinations of world powers, and the United States in particular, in overthrowing the government of the Congo in 1961; and Yance Ford’s Power, a chilling examination of the US police force’s evolution and tainted presence. In Berlin, Rich found that the political turmoil over the war in Gaza couldn’t dim the incandescence of Mati Diop’s Dahomey, winner of the festival’s Golden Bear, which she declares a “masterpiece.”

News organizations increasingly utilize visual elements to communicate news and information to audiences. Digital editing technology allows producers to enhance visual communication through the addition of supplementary text or filters to photos. Such metacommunication can alter the intrinsic meaning of a photograph while increasing audience engagement. Traditional photojournalism norms state that images should not be altered. This study examines whether metacommunicative news images receive more engagement and whether some outlets are more likely than others to share such images.

The Japan Astrometry Satellite Mission for INfrared Exploration (JASMINE) is a planned M-class science space mission by the Institute of Space and Astronautical Science, the Japan Aerospace Exploration Agency. JASMINE has two main science goals. One is Galactic archaeology with a Galactic Center survey, which aims to reveal the Milky Way’s central core structure and formation history from Gaia-level (∼25 ${\mu} $as) astrometry in the near-infrared (NIR) Hwband (1.0–1.6 ${\mu} $m). The other is an exoplanet survey, which aims to discover transiting Earth-like exoplanets in the habitable zone from NIR time-series photometry of M dwarfs when the Galactic Center is not accessible. We introduce the mission, review many science objectives, and present the instrument concept. JASMINE will be the first dedicated NIR astrometry space mission and provide precise astrometric information on the stars in the Galactic Center, taking advantage of the significantly lower extinction in the NIR. The precise astrometry is obtained by taking many short-exposure images. Hence, the JASMINE Galactic Center survey data will be valuable for studies of exoplanet transits, asteroseismology, variable stars, and microlensing studies, including discovery of (intermediate-mass) black holes. We highlight a swath of such potential science, and also describe synergies with other missions.

A ready‐to‐use (RTU) long‐acting injectable (LAI) formulation of aripiprazole monohydrate for administration once every 2 months, available in 960 mg (Ari 2MRTU 960) or 720 mg doses, has been developed for the treatment of schizophrenia or bipolar I disorder. A previously developed and validated population pharmacokinetic model for characterizing aripiprazole plasma concentrations following administration of oral aripiprazole or aripiprazole once‐monthly (AOM) intramuscular injection was expanded to include the RTU LAI formulation of aripiprazole (Ari RTU LAI). Overall, 8899 aripiprazole pharmacokinetic samples from 1191 adults from 10 clinical trials were included in the final combined analysis data set. Aripiprazole plasma concentration‐time profiles were simulated for various Ari RTU LAI initiation and maintenance scenarios in 1000 virtual patients. Diagnostic plots demonstrated that the final population pharmacokinetic model, which incorporated data for oral aripiprazole, AOM, and Ari RTU LAI, adequately described aripiprazole concentrations following Ari RTU LAI administration. Absorption of Ari RTU LAI was modeled by a parallel zero‐order and lagged first‐order process. Simulations across multiple scenarios were performed to inform dosing recommendations, including various treatment initiation regimens for a 2‐monthly formulation of Ari RTU LAI in patients with or without prior stabilization on oral aripiprazole, and for patients switching from AOM. Additional simulations accounted for missed/delayed doses, cytochrome (CYP) 2D6 metabolizer status, and concomitant use of CYP2D6 or CYP3A4 inhibitors. Overall, simulations across a variety of scenarios demonstrated an Ari RTU LAI pharmacokinetic exposure profile that was comparable to AOM, with a longer dosing interval.

Scholars and professionals have discussed that women working in sports media are often targeted by hateful rhetoric on social media. Through the lenses of hegemonic masculinity and online toxicity theories, this study examines X (formerly known as Twitter) mentions directed at both men and women sports reporters, comparing how men and women are harassed and how often. The study also uses a network analysis to examine toxic behaviors and communities directed at sports journalists. The sample of nearly 350,000 mentions was gathered over a 12-year period. Results show that while toxic posts directed at women were no more common than those that were directed at men, the content of the toxic posts were markedly different. The toxic posts directed toward men contained many sports-related themes, such as coaches, games, or team names. The toxic posts toward women were more likely to contain discussions of gender, sex, and sexual assault.

Marcella Liburd, born on July 10, 1953, is a politician from Saint Kitts and Nevis. In 2023, she became the first woman to be appointed as the governor-general of the country. Liburd has been a trailblazer in her career, being the first female speaker in the National Assembly and the first female chair of the Saint Kitts and Nevis Labour Party. She is known for her advocacy for social justice and gender equality, particularly in the drafting of the Equal Pay Act and the Domestic Violence Act. Liburd's inauguration marked a historic moment for the country and she is committed to continuing her efforts in serving the people of Saint Kitts and Nevis. [Extracted from the article]

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The dual jaw joint of Morganucodon1,2consists of the dentary–squamosal joint laterally and the articular–quadrate one medially. The articular–quadrate joint and its associated post-dentary bones constitute the precursor of the mammalian middle ear. Fossils documenting the transition from such a precursor to the mammalian middle ear are poor, resulting in inconsistent interpretations of this hallmark apparatus in the earliest stage of mammaliaform evolution1–5. Here we report mandibular middle ears from two Jurassic mammaliaforms: a new morganucodontan-like species and a pseudotribosphenic shuotheriid species6. The morganucodontan-like species shows many previously unknown post-dentary bone morphologies1,2and exhibits features that suggest a loss of load-bearing function in its articular–quadrate joint. The middle ear of the shuotheriid approaches the mammalian condition in that it has features that are suitable for an exclusively auditory function, although the post-dentary bones are still attached to the dentary. With size reduction of the jaw-joint bones, the quadrate shifts medially at different degrees in relation to the articular in the two mammaliaforms. These changes provide evidence of a gradual loss of load-bearing function in the articular–quadrate jaw joint—a prerequisite for the detachment of the post-dentary bones from the dentary7–12and the eventual breakdown of the Meckel’s cartilage13–15during the evolution of mammaliaforms.

Shuotheriids are Jurassic mammaliaforms that possess pseudotribosphenic teeth in which a pseudotalonid is anterior to the trigonid in the lower molar, contrasting with the tribosphenic pattern of therian mammals (placentals, marsupials and kin) in which the talonid is posterior to the trigonid1–4. The origin of the pseudotribosphenic teeth remains unclear, obscuring our perception of shuotheriid affinities and the early evolution of mammaliaforms1,5–9. Here we report a new Jurassic shuotheriid represented by two skeletal specimens. Their complete pseudotribosphenic dentitions allow reidentification of dental structures using serial homology and the tooth occlusal relationship. Contrary to the conventional view1,2,6,10,11, our findings show that dental structures of shuotheriids can be homologized to those of docodontans and partly support homologous statements for some dental structures between docodontans and other mammaliaforms6,12. The phylogenetic analysis based on new evidence removes shuotheriids from the tribosphenic ausktribosphenids (including monotremes) and clusters them with docodontans to form a new clade, Docodontiformes, that is characterized by pseudotribosphenic features. In the phylogeny, docodontiforms and ‘holotherians’ (Kuehneotherium, monotremes and therians)13evolve independently from a Morganucodon-like ancestor with triconodont molars by labio-lingual widening their posterior teeth for more efficient food processing. The pseudotribosphenic pattern passed a cusp semitriangulation stage9, whereas the tribosphenic pattern and its precursor went through a stage of cusp triangulation. The two different processes resulted in complex tooth structures and occlusal patterns that elucidate the earliest diversification of mammaliaforms.