bluuebunny/crossref_metadata_2025 huggingface dataset:
High-salt diet induces microbiome dysregulation, neuroinflammation and anxiety in the chronic period after mild repetitive closed head injury in adolescent mice
Authors: Izzy Saef , Yahya Taha , Albastaki Omar , Cao Tian , Schwerdtfeger Luke A , Abou-El-Hassan Hadi , Chopra Kusha , Ekwudo Millicent N , Kurdeikaite Ugne , Verissimo Isabelly M , LeServe Danielle S , Lanser Toby B , Aronchik Michael , Oliveira Marilia G , Moreira Thais , Rezende Rafael Machado , El Khoury Joseph , Cox Laura M , Weiner Howard L , Zafonte Ross , Whalen Michael J
Published: May 2024

The associations between human concussions and subsequent sequelae of chronic neuropsychiatric and cardiovascular diseases such as hypertension have been reported; however, little is known about the underlying biological processes. We hypothesized that dietary changes, including a high-salt diet, disrupt the bidirectional gut–brain axis, resulting in worsening neuroinflammation and emergence of cardiovascular and behavioural phenotypes in the chronic period after repetitive closed head injury in adolescent mice. Adolescent mice were subjected to three daily closed head injuries, recovered for 12 weeks and then maintained on a high-salt diet or a normal diet for an additional 12 weeks. Experimental endpoints were haemodynamics, behaviour, microglial gene expression (bulk RNA sequencing), brain inflammation (brain tissue quantitative PCR) and microbiome diversity (16S RNA sequencing). High-salt diet did not affect systemic blood pressure or heart rate in sham or injured mice. High-salt diet increased anxiety-like behaviour in injured mice compared to sham mice fed with high-salt diet and injured mice fed with normal diet. Increased anxiety in injured mice that received a high-salt diet was associated with microgliosis and a proinflammatory microglial transcriptomic signature, including upregulation in interferon-gamma, interferon-beta and oxidative stress–related pathways. Accordingly, we found upregulation of tumour necrosis factor-alpha and interferon-gamma mRNA in the brain tissue of high salt diet–fed injured mice. High-salt diet had a larger effect on the gut microbiome composition than repetitive closed head injury. Increases in gut microbes in the families Lachnospiraceae, Erysipelotrichaceae and Clostridiaceae were positively correlated with anxiety-like behaviours. In contrast, Muribaculaceae, Acholeplasmataceae and Lactobacillaceae were negatively correlated with anxiety in injured mice that received a high-salt diet, a time-dependent effect. The findings suggest that high-salt diet, administered after a recovery period, may affect neurologic outcomes following mild repetitive head injury, including the development of anxiety. This effect was linked to microbiome dysregulation and an exacerbation of microglial inflammation, which may be physiological targets to prevent behavioural sequelae in the chronic period after mild repetitive head injury. The data suggest an important contribution of diet in determining long-term outcomes after mild repetitive head injury.
Wearing their heart on a wall: the World’s Biggest Comic
Authors: Martinez Lee , Granek-Dennis Kasia , Parker Richard , Taylor Judy
Published: May 2024

An arts-based project, using a community development approach engaging people in a community of place to address suicide prevention, is potentially powerful. This involves linking community development and mental health promotion practice. The challenge in doing this is that, conceptually, the integration between the two is incomplete and there is a lack of guidance about effective community processes. This paper analyses community development processes to create the World’s Biggest Comic (WBC). The WBC was an innovative, large scale public art project engaging local artists, some with a lived experience of mental illness, to tell a story of Will and Hope. A 15-part comic story, printed on vinyl canvas panels and mounted on buildings, covered 600 m2. https://www.facebook.com/watch/?v=217471332673743 Conducted in a small rural South Australian community by the local volunteer Suicide Prevention Network, the WBC aimed to raise awareness, break down stigma, and prompt life-saving conversations. Results of a mixed method impact evaluation are presented using a community development framework that considers ‘people’, ‘space’, and ‘place’. The use of sociological concepts about community and the community field, the value of relationships, and listening to the voices of those with a lived experience of mental illness, may assist practice. Some potential learnings and pitfalls in using a community development approach in mental health promotion are discussed.
Contracting in the Public Interest? Re-examining the Role of Planning Obligations in Contemporary Town Planning Processes
Authors: Mitchell Edward
Published: May 2024

This article investigates how local authorities in England seek to compel property developers to mitigate the impact of property development on local communities and on local infrastructure needs through the use of planning obligations made by agreement with developers pursuant to section 106 of the Town and Country Planning Act 1990. I pose three important new questions about these ‘section 106 agreements’. How do these agreements contribute to a development culture in which private developers do not always perform their public policy obligations? How does the presence of ostensibly binding promises in these agreements facilitate the exercise of regulatory decision-making in planning and property development processes? How do local authorities manage the implementation of novel developer obligations designed to shape broader community relations? I answer these questions by examining two case study development projects. In doing so, I highlight the limited role that these agreements have as an instrument for ordering the ‘private’ relations between a local authority and a developer. I then look outside the private ordering function of these agreements to scrutinise the public-facing work they do. Here, I highlight how a section 106 agreement carries a powerful expressive force, despite its weakness as a private ordering device, that developers and local authorities can use to justify contentious development proposals involving coercive compulsory purchase powers and potentially adverse equalities implications. The article thus adds to what is already known about the use and implementation of planning obligations, and sketches a research agenda that would inform debate about the future of this area of planning practice.
Remote Between Visit Monitoring in Inflammatory Bowel Disease Care: A Qualitative Study of CAPTURE-IBD Participants and Care Team Members
Authors: Aintabi Daniel , Greenberg Gillian , Berinstein Jeffrey A , DeJonckheere Melissa , Wray Daniel , Sripada Rebecca K , Saini Sameer D , Higgins Peter D R , Cohen-Mekelburg Shirley
Published: May 2024

Introduction

We recently showed that CAPTURE-inflammatory bowel disease (IBD)—a care coordination intervention comprised of routine remote monitoring of patient-reported outcomes (PRO) and a care coordinator-triggered care pathway—was more effective at reducing symptom burden for patients with IBD compared to usual care. We aimed to understand how patients and care team providers experienced the intervention and evaluate purported mechanisms of action to plan for future implementation.

Methods

In this study, 205 patients were randomized to CAPTURE-IBD (n = 100) or usual care(n = 105). We conducted semi-structured interviews with 16 of the 100 participants in the CAPTURE-IBD arm and 5 care team providers to achieve thematic saturation. We used qualitative rapid analysis to generate a broad understanding of experiences, perceived impact, the coordinator role, and suggested improvements.

Results

Findings highlight that the intervention was acceptable and user-friendly, despite concerns regarding increased nursing workload. Both participants and care team providers perceived the intervention as valuable in supporting symptom monitoring, psychosocial care, and between-visit action plans to improve IBD care and health outcomes. However, few participants leveraged the care coordinator as intended. Finally, participants reported that the intervention could be better tailored to capture day-to-day symptom changes and to meet the needs of patients with specific comorbid conditions (eg, ostomies).

Conclusions

Remote PRO monitoring is acceptable and may be valuable in improving care management, promoting tight control, and supporting whole health in IBD. Future efforts should focus on testing and implementing refined versions of CAPTURE-IBD tailored to different clinical settings.
Transcatheter management of obstructed baffle repairs of partial anomalous pulmonary veins: a case series
Authors: Das Thomas M , Blazevic Patricia , Mehra Nandini , Bakhtadze Beka , Ghobrial Joanna
Published: May 2024

Background

Partial anomalous pulmonary venous return (PAPVR) can be surgically corrected using a pericardial baffle. This baffle can become obstructed post-surgery, leading to pulmonary hypertension and right heart dysfunction if not detected and corrected.

Case summary

We describe three patients with occluded PAPVR baffles who underwent drug-coated balloon angioplasty and stenting of the obstructed baffle. In each case, baffle obstruction was detected post-operatively on surveillance cross-sectional imaging, and an invasively measured pulmonary capillary wedge-to-left atrium gradient was noted to be elevated. Post-intervention, each patient had an improvement in baffle flow by angiography as well as lung perfusion as assessed by nuclear medicine scintigraphy.

Discussion

Given the subtle symptomatology of obstructed PAPVR pericardial baffle repairs, surveillance imaging is necessary to detect occluded baffles and intervene before downstream right heart disease and pulmonary hypertension develops. Given the high rates of re-stenosis in pulmonary vein stenting, pre-treatment of occluded PAPVR baffles with drug-coated balloons may help reduce re-intervention rates.
Age at menopause and risk of ischaemic stroke: a systematic review and meta-analysis
Authors: Wang Jie , Chen Ying
Published: May 2024

Aims

Despite ischaemic stroke having much importance as one of the top 10 causes of death in older women, there are limited data on age at menopause and ischaemic stroke. We performed a systematic review and meta-analysis to estimate the effect of age at menopause on ischaemic stroke.

Methods and results

We screened four databases (PubMed, Cochrane, Web of Science, and EMBASE databases) up to 17 July 2023. This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered with PROSPERO (CRD42023444245). Data extraction and quality assessment were independently undertaken by two reviewers. A random-effects model was used for meta-analysis using Revman5.4 to calculate the risk ratio of the incidence of ischaemic stroke. Heterogeneity was assessed using I2. Meta-regression and assessment for bias were performed. Out of 725 records identified, 10 studies were included in the qualitative synthesis and the quantitative meta-analysis. The pooled incidence rate for ischaemic strokes which age at menopause before 43 years old was 1.22 [95% confidence interval (CI): 1.02–1.46]. The pooled incidence rate of early menopause was 1.26 (95% CI: 1.07–1.48) for ischaemic stroke. The incidence rate of ischaemic stroke for women with early menopause may be in an environment with a high incidence for a long time.

Conclusion

This meta-analysis suggests that early menopause is associated with an increased risk of ischaemic stroke. Age at onset of menopause before 43 years old may be the cut-off value of increased risk of ischaemic stroke.
Misperceptions, Depression, and Voting for Election Deniers in the United States
Authors: Baum Matthew A , Druckman James N , Ognyanova Katherine , Schulman Jonathan
Published: May 2024

Two of the most significant concerns about the contemporary United States are the erosion of democratic institutions and the high rate of depression. We provide evidence connecting these phenomena. We use a survey (N = 11,517) to show a relationship between misperceptions (about COVID-19 vaccines) and voting, in 2022, for gubernatorial candidates who denied or cast doubt on the legitimacy of the 2020 election results. We further predict and find that the presence of moderately severe-to-severe depressive symptoms exacerbates the relationship between misperceptions and voting for election deniers or doubters. The results offer insight into the links between misperceptions, depression, and democratic backsliding (i.e., supporting candidates who challenge election results). We also contribute to a growing line of research on how mental health affects democratic functioning, potentially worldwide.
The Nuclear Nonproliferation Regime as a “Failed Promise”: Contestation and Self-Undermining Dynamics in a Liberal Order
Authors: Tannenwald Nina
Published: May 2024

The Nuclear Nonproliferation Treaty (NPT) forms the core of the most prominent multilateral security governance regime of the liberal international order (LIO). Despite being a widely supported and remarkably successful security regime to prohibit the spread of nuclear weapons, NPT politics have become increasingly polarized. In this article, I analyze contestation and self-undermining dynamics in the nuclear regime. The NPT is a strongly institutionalized but weakly liberal regime. However, it is unevenly institutionalized. Patterns of contestation in the regime derive from these characteristics. The basic source of contestation is the fundamental inequality between the nuclear “haves” and “have-nots.” Specifically, dissatisfied states seek to strengthen the rules and obligations in the less institutionalized domain. I argue that when efforts at order-consistent reform fail, states shift to a more radical strategy of liberal counter-institutionalization to pursue their goal of equality. Nonnuclear states have long been dissatisfied with the uneven distribution of the burdens and benefits of the regime, and especially the nuclear-armed states’ failure to pursue their obligation of disarmament. Most of the contestation in the NPT over the decades has been order-consistent and pursued “liberal reform.” However, when proponents of nuclear disarmament failed to achieve meaningful progress through the NPT, they shifted to a liberal counter-institutionalization strategy and adopted an entirely new legal instrument, the 2017 Nuclear Prohibition Treaty, to pursue disarmament. This was a direct—but liberal—challenge to the existing suborder. This treaty, which prohibits nuclear weapons for all, legalizes the NPT obligation to pursue disarmament.
A phase I/II study of nintedanib and capecitabine for refractory metastatic colorectal cancer
Authors: Boland Patrick M , Ebos John M L , Attwood Kristopher , Mastri Michalis , Fountzilas Christos , Iyer Renuka V , Banker Christopher , Goey Andrew K L , Bies Robert , Ma Wen Wee , Fakih Marwan
Published: May 2024

Background

Nintedanib is a tyrosine kinase inhibitor with efficacy in bevacizumab-resistant colorectal cancer models. This phase I/II study evaluated the recommended phase II dose and efficacy of nintedanib and capecitabine in refractory metastatic colorectal cancer.

Methods

Key eligibility criteria included refractory metastatic colorectal cancer and ECOG performance status of 1 or lower. The primary endpoint was 18-week progression-free survival (PFS). A 1-sided binomial test (at α = .1) compared the observed 18-week PFS with a historic control of .25.

Results

Forty-two patients were enrolled, including 39 at the recommended phase II dose. The recommended phase II dose was established to be nintedanib 200 mg by mouth twice daily and capecitabine 1000 mg/m2 by mouth twice daily. The protocol was evaluated for efficacy in 36 patients. The 18-week PFS was 42% (15/36 patients; P = .0209). Median PFS was 3.4 mo. Median overall survival was 8.9 mo. Sixteen (44%) patients experienced a grade 3/4 adverse event, most commonly fatigue (8%), palmoplantar erythrodysesthesia (8%), aspartate aminotransferase elevation (6%), asthenia (6%), pulmonary embolus (6%), and dehydration (6%). Osteopontin levels at cycle 1, day 1 and cycle 3, day 1 as well as ΔCCL2 levels correlated to disease control at 18 weeks.

Conclusions

The combination of nintedanib and capecitabine is well tolerated. Clinical efficacy appears to be superior to regorafenib or tipiracil hydrochloride monotherapy. Further investigation of similar combinations is warranted.

ClinicalTrials.gov identifier

NCT02393755
Stormwise: Innovative Forest Management to Promote Storm Resistance in Roadside Forests
Authors: Worthley Thomas , Bunce Amanda , Morzillo Anita T , Witharana Chandi , Zhu Zhe , Cabral Jacob , Crocker Emlyn , Cranmer Nicholas , DiFalco Steven , Hale Daniel , Joshi Durga , Kloster Danielle P , Marek Nancy , Parent Jason , Rogers Julia , Rudnicki Mark , Song Kexin , Volin John , Ward Jeffrey , Wedagedara Harshana , Fahey Robert T
Published: May 2024

A growing proportion of forested landscapes are interspersed with human infrastructure, such as utility lines and roads, increasing the potential for tree-failure consequences due to storms and other causes. Utilities and other institutions have strong incentives to reduce such interactions and allocate substantial resources to risk reduction, but trees and forests in densely populated landscapes also provide significant amenities to society. We present a generalized framework for “Stormwise” forest management, focused on resistance of roadside forests to storms, based on elements of arboricultural and silvicultural practice and tree biomechanics and architecture. We detail results of a multidisciplinary research program focused on management outcomes, opportunities and barriers to implementation, and allocation of investment based on physical and social landscape characteristics. We discuss initial findings, the potential for widespread adoption of resilience-focused management in roadside and infrastructure-adjacent forests, and the importance of such work, considering a changing climate.

Study Implications: The research and implementation program we detail here illustrates the potential for “Stormwise” forest management to reduce storm-damage recovery costs, result in fewer and shorter-duration power and transportation interruptions, and allow for low-investment ground-based management in future forest entries. We illustrate a multifaceted, interdisciplinary research program that links the geospatial, social, and biophysical components of understanding forest infrastructure systems. We illustrate how implementation of Stormwise management has the potential to benefit stakeholders such as residents and utilities, offset the substantial economic costs of tree-related power outages, and reduce societal disruptions associated with interactions between trees and infrastructure during storms.
Unveiling Motivations: Military Women's Incorporation into the Brazilian Armed Forces
Authors: Neumann Isabella , Pagliari Graciela de Conti
Published: May 2024

This article offers a meticulous examination of the underlying incentives that led to the integration of women into the Brazilian Armed Forces. Employing content analysis and discourse analysis, the present study investigates a range of legal landmarks, legislative propositions, presidential communiqués, and parliamentary transcripts spanning the time spectrum from 1930 to 2020. In doing so, it constructs a historical panorama that elucidates the multifaceted and sometimes incongruous trajectory of the incorporation of military women into the fabric of the Brazilian military institution. The discerned results of this investigation conclude that a confluence of factors drove the inclusion of women in the military ranks. These factors include the need for a greater workforce, alignment with international conventions, and the projection of a modern symbol of the Armed Forces in the domestic environment—while gender parity remained a secondary objective.
Using the consolidated framework for implementation research to identify challenges and opportunities for implementing a reproductive health education program into sickle cell disease care
Authors: Colton Zachary A , Liles Sophia M , Griffith Megan M , Stanek Charis J , Walden Joseph , King Allison , Barnard-Kirk Toyetta , Creary Susan , Nahata Leena
Published: May 2024

Background

As survival rates for individuals with sickle cell disease (SCD) increase, calls have been made to improve their reproductive healthcare and outcomes. The research team created a web-based program entitled Fertility edUcaTion to Understand ReproductivE health in Sickle cell disease (FUTURES). The study aim was to use the Consolidated Framework for Implementation Research (CFIR) during pre-implementation to identify challenges and opportunities from the individual to systems level of implementation to ultimately optimize the integration of FUTURES into clinical practice.

Methods

Semi-structured interviews were conducted with clinicians, research team members, and adolescent and young adult (AYA) males with SCD and their caregivers who participated in pilot testing. Interviews (N = 31) were coded inductively and then mapped onto CFIR domains (i.e., outer setting, inner setting, characteristics of individuals, and intervention characteristics).

Results

Research team interviews indicated the lack of universal guidelines for reproductive care in this population and gaps in reproductive health knowledge as key reasons for developing FUTURES, also highlighting the importance of collaboration with community members during development. Clinicians reported intraorganizational communication as essential to implementing FUTURES and discussed challenges in addressing reproductive health due to competing priorities. Clinicians, AYAs, and caregivers reported positive views of FUTURES regarding length, engagement, accessibility, and content. Suggestions for the best setting and timing for implementation varied.

Conclusions

Using CFIR during the pre-implementation phase highlighted challenges and opportunities regarding integrating this program into SCD care. These findings will inform adaptation and further testing of FUTURES to ensure effective implementation of this novel education program.
Enhancing biliary structure identification using percutaneous cholecystostomy drain delivery of indocyanine green: a glowing two case review
Authors: Alexander Peter , Marcucci Vincent , Torres Patricia , Cassidy Jillian , Kipnis Seth , Arumugam Dena
Published: May 2024

The use of indocyanine green for fluorescent cholangiography in patients with cholecystitis initially treated with percutaneous cholecystostomy drainage catheters was described in this two case series. Two patients underwent robotic assisted cholecystectomy with fluorescent cholangiography and indocyanine green through percutaneous cholecystostomy drainage catheters. The patients were diagnosed with acute cholecystitis. Directed injection of indocyanine green allowed for direct visualization of the biliary system allowing for a safe identification of the critical view of safety. Injection of indocyanine green for fluorescent cholangiography through percutaneous cholecystostomy drainage catheters is reliable to assess the critical view of safety and allows for improved identification of the biliary tree anatomy. Administration of indocyanine green through the percutaneous cholecystostomy drainage catheters avoided background hepatic fluorescence and increased contrast between biliary structures.
An imaging and diagnostic conundrum—the adrenal haemangioma
Authors: Tan Tiffany , Diab Jason , Chia Philip , Singh Amandeep , Campbell Peter , Guevara Ronald
Published: May 2024

The adrenal haemangioma, a rare benign vascular tumour, is increasingly detected through abdominal imaging. Just over 70 surgical cases have been reported since 1955. Their potential large size and overlapping imaging features with adrenocortical carcinoma poses a diagnostic challenge. Adrenalectomy is often needed for a definitive diagnosis due to inconclusive imaging. We report the case of a 61-year-old female presenting with an incidental finding of a right-sided 9.5-cm adrenal mass on imaging. Due to the risk of adrenocortical carcinoma with inconclusive imaging findings, an open right adrenalectomy was performed. The patient was discharged after 6 days with no complications. Post-surgical histopathology confirmed a diagnosis of adrenal haemangioma with a secondary adrenal pseudocyst. The presence of an adrenal incidentaloma with discordant radiological features proves to be a diagnostic conundrum. Therefore, in the setting of contradictory radiology and concerning mass size, we recommend adrenalectomy for definitive diagnosis of an adrenal haemangioma.
Cellular senescence induced by down-regulation of PTBP1 correlates with exon skipping of mitochondrial-related gene NDUFV3
Authors: Yang Yu , Wen Haimei , Li Yuxin , Zeng Xin , Wei Gang , Gu Zhenglong , Ni Ting
Published: May 2024

As the most prevalent type of alternative splicing in animal cells, exon skipping plays an important role in expanding the diversity of transcriptome and proteome, thereby participating in the regulation of diverse physiological and pathological processes such as development, aging, and cancer. Cellular senescence serving as an anti-cancer mechanism could also contribute to individual aging. Although the dynamic changes of exon skipping during cellular senescence were revealed, its biological consequence and upstream regulator remain poorly understood. Here, by using human foreskin fibroblasts (HFF) replicative senescence as a model, we discovered that splicing factor PTBP1 was an important contributor for global exon skipping events during senescence. Down-regulated expression of PTBP1 induced senescence-associated phenotypes and related mitochondrial functional changes. Mechanistically, PTBP1 binds to the third exon of mitochondrial complex I subunit coding gene NDUFV3 and protects the exon from skipping. We further confirmed that exon skipping of NDUFV3 correlates with and partially contributes to cellular senescence and related mitochondrial functional changes upon PTBP1 knockdown. Together, we revealed for the first time that mitochondrial-related gene NDUFV3 is a new downstream target for PTBP1-regulated exon skipping to mediate cellular senescence and mitochondrial functional changes.
A study of Galactic Plane Planck Galactic cold clumps observed by SCOPE and the JCMT Plane Survey
Authors: Eden D J , Liu Tie , Moore T J T , Di Francesco J , Fuller G , Kim Kee-Tae , Li Di , Liu S -Y , Plume R , Tatematsu Ken’ichi , Thompson M A , Wu Y , Bronfman L , Butner H M , Currie M J , Garay G , Goldsmith P F , Hirano N , Johnstone D , Juvela M , Lai S-P , Lee C W , Mannfors E E , Olguin F , Pattle K , Park Geumsook , Polychroni D , Rawlings M , Rigby A J , Sanhueza P , Traficante A , Urquhart J S , Weferling B , White G J , Yadav R K
Published: May 2024

We have investigated the physical properties of Planck Galactic Cold Clumps (PGCCs) located in the Galactic Plane, using the JCMT Plane Survey (JPS) and the SCUBA-2 Continuum Observations of Pre-protostellar Evolution (SCOPE) survey. By utilizing a suite of molecular-line surveys, velocities, and distances were assigned to the compact sources within the PGCCs, placing them in a Galactic context. The properties of these compact sources show no large-scale variations with Galactic environment. Investigating the star-forming content of the sample, we find that the luminosity-to-mass ratio (L/M) is an order of magnitude lower than in other Galactic studies, indicating that these objects are hosting lower levels of star formation. Finally, by comparing ATLASGAL sources that are associated or are not associated with PGCCs, we find that those associated with PGCCs are typically colder, denser, and have a lower L/M ratio, hinting that PGCCs are a distinct population of Galactic Plane sources.
The Designed Ankyrin Repeat Protein Antiviral Ensovibep for Nonhospitalized Patients With Coronavirus Disease 2019: Results From EMPATHY, a Randomized, Placebo-Controlled Phase 2 Study
Authors: Kingsley Jeff , Kumarasamy Nagalingeswaran , Abrishamian Luis , Bonten Marc , Igbinadolor Awawu , Mekebeb-Reuter Martha , Rosa Jennifer , Solai Elango Damodaran , Lopez Patricia , Fustier Pierre , Goncalves Susana , Knutson Charles G , Kukkaro Petra , Legenne Philippe , Ramanathan Krishnan , Rao Shantha , Reshetnyak Evgeniya , Stavropoulou Vaia , Stojcheva Nina , Stumpp Michael T , Tietz Andreas , Soergel Marianne , Chandra Richa
Published: May 2024

Background

The coronavirus disease 2019 (COVID-19) pandemic was characterized by rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, affecting viral transmissibility, virulence, and response to vaccines/therapeutics. EMPATHY (NCT04828161), a phase 2 study, investigated the safety/efficacy of ensovibep, a multispecific designed ankyrin repeat protein (DARPin) with multivariant in vitro activity, in ambulatory patients with mild to moderate COVID-19.

Methods

Nonhospitalized, symptomatic patients (N = 407) with COVID-19 were randomized to receive single-dose intravenous ensovibep (75, 225, or 600 mg) or placebo and followed until day 91. The primary endpoint was time-weighted change from baseline in log10 SARS-CoV-2 viral load through day 8. Secondary endpoints included proportion of patients with COVID-19–related hospitalizations, emergency room (ER) visits, and/or all-cause mortality to day 29; time to sustained clinical recovery to day 29; and safety to day 91.

Results

Ensovibep showed superiority versus placebo in reducing log10 SARS-CoV-2 viral load; treatment differences versus placebo in time-weighted change from baseline were −0.42 (P = .002), −0.33 (P = .014), and −0.59 (P < .001) for 75, 225, and 600 mg, respectively. Ensovibep-treated patients had fewer COVID-19–related hospitalizations, ER visits, and all-cause mortality (relative risk reduction: 78% [95% confidence interval, 16%–95%]) and a shorter median time to sustained clinical recovery than placebo. Treatment-emergent adverse events occurred in 44.3% versus 54.0% of patients in the ensovibep and placebo arms; grade 3 events were consistent with COVID-19 morbidity. Two deaths were reported with placebo and none with ensovibep.

Conclusions

All 3 doses of ensovibep showed antiviral efficacy and clinical benefits versus placebo and an acceptable safety profile in nonhospitalized patients with COVID-19.
Examining a hadronic γ-ray scenario for the radiative shell and molecular clouds of the old GeV supernova remnant G298.6−0.0
Authors: Yeung Paul K H , Lee Shiu-Hang , Mizuno Tsunefumi , Bamba Aya
Published: May 2024

Based on the 13.7 yr Fermi-LAT data, Yeung, Bamba, and Sano (2023, PASJ, 75, 384) claimed detection of two γ-ray sources (namely Src-NE and Src-NW) associated with the supernova remnant (SNR) G298.6−0.0, and interpreted it as an old GeV SNR interacting with molecular clouds (MCs). In this follow-up study, we refine the flux measurements below 2 GeV with Fermi-LAT event types of better angular reconstruction. Then, we report our γ-ray spectral fittings and cosmic-ray phenomenology in a hadronic scenario, considering both the shell and MC regions of SNR G298.6−0.0. We confirm that the γ-ray spectra of both Src-NE and Src-NW exhibit spectral breaks, at $1.50_{-0.50}^{+0.60}$ and $0.68_{-0.11}^{+0.32}\:$GeV, respectively. Src-NW has a harder broad-band photon index than Src-NE, suggesting an appreciable difference between the physical separations of their respective emission sites from SNR G298.6−0.0. The cosmic-ray spectrum responsible for Src-NE starts with a minimum energy $E_\mathrm{CR,min}=1.38_{-0.16}^{+0.47}\:$GeV, and has a proton index $\Gamma _\mathrm{CR}=2.57_{-0.21}^{+0.18}$ below the exponential cutoff energy $E_\mathrm{CR,max}=240_{-150}^{+240}\:$GeV. Accordingly, we argue that Src-NE is dominated by the SNR shell, while only a minor portion of lower-energy emission is contributed by the MCs interacting with the SNR. The cosmic-ray population for Src-NW starts at a higher energy such that the ECR, min ratio of Src-NW to Src-NE is ≳2. The high ECR, min, as well as the high cosmic-ray energy density required (∼26 eV cm−3), supports the interpretation that Src-NW is predominantly the γ-ray emission from the farther MCs being bombarded by protons that had earlier escaped from SNR G298.6−0.0. By comparing the high-energy features of G298.6−0.0 with those of analogical SNRs, especially SNR W 28 and SNR W 44, we further constrain the age of SNR G298.6−0.0 to be 10–30 kyr, under the assumption of a purely hadronic scenario.
The deadliest local police departments kill 6.91 times more frequently than
the least deadly departments, net of risk, in the United States
Authors: Leung-Gagné Josh
Published: May 2024

I use data linking counts of homicides by police to police department (PD)
and jurisdiction characteristics to estimate benchmarked (i.e. risk-adjusted)
police homicide rates in 2008–2017 among the 711 local PDs serving 50,000 or more
residents, a sample with demographics resembling all mid-to-large Census places.
The benchmarked rate estimates capture PD deadliness by comparing PDs to peers
whose officers face similar risks while adjusting for access to trauma care
centers to account for differential mortality from deadly force. Compared to
existing estimates, differences in benchmarked estimates are more plausibly
attributable to policing differences, speaking to whether the force currently used
is necessary to maintain safety and public order. I find that the deadliest PDs
kill at 6.91 times the benchmarked rate of the least deadly PDs. If the PDs with
above-average deadliness instead killed at average rates for a PD facing similar
risks, police homicides would decrease by 34.44%. Reducing deadliness to the
lowest observed levels would decrease them by 70.04%. These estimates also
indicate the percentage of excess police homicides—those unnecessary for
maintaining safety—if the baseline agency is assumed to be optimally deadly.
Moreover, PD deadliness has a strong, robust association with White/Black
segregation and Western regions. Additionally, Black, Hispanic, foreign-born,
lower income, and less educated people are disproportionately exposed to deadlier
PDs due to the jurisdictions they reside in. Police violence is an important
public health concern that is distributed unevenly across US places, contributing
to social disparities that disproportionately harm already marginalized
communities.
Intrinsic functional connectivity of motor and heteromodal association cortex predicts individual differences in regulatory focus
Authors: Kim Nayoung , Kim M Justin , Strauman Timothy J , Hariri Ahmad R
Published: May 2024

Regulatory focus theory (RFT) describes two cognitive–motivational systems for goal pursuit—the promotion and prevention systems—important for self-regulation and previously implicated in vulnerability to psychopathology. According to RFT, the promotion system is engaged in attaining ideal goals (e.g. hopes and dreams), whereas the prevention system is associated with accomplishing ought goals (e.g. duties and obligations). Prior task-based functional magnetic resonance imaging (fMRI) studies have mostly explored the mapping of these two systems onto the activity of a priori brain regions supporting motivation and executive control in both healthy and depressed adults. However, complex behavioral processes such as those guided by individual differences in regulatory focus are likely supported by widely distributed patterns of intrinsic functional connectivity. We used data-driven connectome-based predictive modeling to identify patterns of distributed whole-brain intrinsic network connectivity associated with individual differences in promotion and prevention system orientation in 1,307 young university volunteers. Our analyses produced a network model predictive of prevention but not promotion orientation, specifically the subjective experience of successful goal pursuit using prevention strategies. The predictive model of prevention success was highlighted by decreased intrinsic functional connectivity of both heteromodal association cortices in the parietal and limbic networks and the primary motor cortex. We discuss these findings in the context of strategic inaction, which drives individuals with a strong dispositional prevention orientation to inhibit their behavioral tendencies in order to shield the self from potential losses, thus maintaining the safety of the status quo but also leading to trade-offs in goal pursuit success.
Abortion Opinion and Partisan Choice: Untangling the Causal Dynamics
Authors: Erikson Robert S
Published: May 2024

Starting in the 1980s, U.S. voters began dividing on the abortion issue into pro-life Republicans and pro-choice Democrats. This study shows that the predominant direction of causality was that abortion opinion caused changes in partisanship rather than the reverse, which then had downstream consequences for vote choice. Working with the Youth Parent Socialization Panel Study, I show that those taking pro-choice and pro-life positions in 1982 subsequently changed their party identification to align with those views. By contrast, Democrats and Republicans, as of 1982, did not realign their abortion positions. The partisan conversions were concentrated among ideologically engaged (IE) respondents, especially IE women, who found themselves out of step with their party on abortion. By triggering changes in party identification, panelists’ abortion stances as early as 1982 influenced their vote choices downstream in the 1996 presidential election. Thus, issue-based realignment is viewed here in real time with data from a panel study.
Schizophrenia Spectrum Disorders: An Empirical Benchmark Study of Real-world Diagnostic Accuracy and Reliability Among Leading International Psychiatrists
Authors: Urkin Bar , Parnas Josef , Raballo Andrea , Koren Danny
Published: May 2024

Background and hypothesis

Assigning a psychiatric diagnosis in real-world situations is often difficult, given that the clinical presentation does not usually conform to the list of condensed, simplified behavioral descriptors of mainstream operational taxonomies (MOT) (eg, ICD-11 and DSM-5). The goal of this study was to benchmark diagnostic accuracy and reliability on a central and severe spectrum of psychopathology (ie, the schizophrenia spectrum disorders [SSDs]), adopting a pragmatic approach as close as possible to real-world clinical settings.

Study Design

We examined the diagnostic performance of 30 international psychiatrists experts in SSD. The clinicians were asked to make their clinical best diagnostic estimate for two written clinical vignettes excerpted from real-world SSD cases.

Study Results

In the first vignette, 22 out of the 30 clinicians (73.5%) indicated a SSD as their main diagnostic hypothesis. In the second vignette, 12 clinicians (40%) chose SSD as their main diagnostic hypothesis. Only 10 of the 30 clinicians (33%) correctly identified both vignettes as cases of SSD. The level of interrater diagnostic agreement (Fleiss’ Kappa) was low but statistically significant (KFleiss = 0.08, P = .01).

Conclusions

The results suggest that, even in a sample of influential international psychiatrists, the diagnostic accuracy and reliability on SSD presentations is poor and substantially inferior to those obtained in reliability studies using structured or semi-structured interviews. The widespread adoption of MOT systems in the last decades may have inadvertently eroded the ability of clinicians to detect a typical pattern of psychiatric illnesses.
Variations in colostrum metabolite profiles in association with sow parity
Authors: Vötterl Julia C , Schwartz-Zimmermann Heidi E , Lerch Frederike , Yosi Fitra , Sharma Suchitra , Aigensberger Markus , Rennhofer Patrick M , Berthiller Franz , Metzler-Zebeli Barbara U
Published: May 2024

Information about the full spectrum of metabolites present in porcine colostrum and factors that influence metabolite abundances is still incomplete. Parity number appears to modulate the concentration of single metabolites in colostrum. This study aimed to 1) characterize the metabolome composition and 2) assess the effect of parity on metabolite profiles in porcine colostrum. Sows (n = 20) were divided into three parity groups: A) sows in parity 1 and 2 (n = 8), B) sows in parity 3 and 4 (n = 6), and C) sows in parity 5 and 6 (n = 6). Colostrum was collected within 12 h after parturition. A total of 125 metabolites were identified using targeted reversed-phase high-performance liquid chromatography-tandem mass spectrometry and anion-exchange chromatography-high resolution mass spectrometry. Gas chromatography additionally identified 19 fatty acids (FAs). Across parities, colostrum was rich in creatine and creatinine, 1,3-dioleyl-2-palmitatoylglycerol, 1,3-dipalmitoyl-2-oleoylglycerol, and sialyllactose. Alterations in colostrum concentrations were found for eight metabolites among parity groups (P < 0.05) but the effects were not linear. For instance, colostrum from parity group C comprised 75.4% more valine but 15.7%, 34.1%, and 47.9% less citric, pyruvic, and pyroglutamic acid, respectively, compared to group A (P < 0.05). By contrast, colostrum from parity group B contained 39.5% more spermidine than from group A (P < 0.05). Of the FAs, C18:1, C16:0, and C18:2 n6 were the main FAs across parities. Parity affected four FAs (C18:3n3, C14:1, C17:0ai, and C17:1), including 43.1% less α-linolenic acid (C18:3n3) in colostrum from parity group C compared to groups A and B (P < 0.05). Signature feature ranking identified 1-stearoyl-2-hydroxy-sn-glycero-3-phosphatidylcholine and the secondary bile acid hyodeoxycholic acid as the most discriminative metabolites, showing a higher variable importance in the projection score in colostrum from parity group A than from groups B and C. Overall, results provided a comprehensive overview about the metabolome composition of sow colostrum. The consequences of the changes in colostrum metabolites with increasing parity for the nutrient supply of the piglets should be investigated in the future. The knowledge gained in this study could be used to optimize feeding strategies for sows.
The combined effect of diffuse radiation and leaf wetness on functional traits and transpiration efficiency on a cloud forest species
Authors: Garcia-Tejera Omar , Ritter Axel , Regalado Carlos M
Published: May 2024

Cloud forests are unique biomes that thrive in foggy environments for a substantial part of the season. Fog in cloud forests plays two critical roles: it reduces incoming radiation and creates a humid environment, leading to the wetting of the canopy. This paper aims to investigate the combined effect of both radiation and wetness on Myrica faya Wilbur—a cloud forest species present in subtropical regions—both directly in plants and through simulations. Experiments consisted of a controlled environment with two levels of radiation and leaf wetness: low radiation/wet conditions, and high radiation/no-wetness; and three treatments: continuous low radiation and wetness, continuous high radiation and no wetness and alternate high low radiation and alternate wetness. The results revealed that a combination of low radiation and leaf wetness significantly improves leaf stomata conductance and increases the specific leaf area (SLA). Changes in SLA were driven by leaf size changes. However, the minimum leaf conductance (gmin) did not respond to any of the treatments. The simulations focused on exploring the impact of radiation and canopy wetness on transpiration efficiency (TE), i.e. the ratio between photosynthesis (An) and transpiration (Tc). The simulations demonstrated that TE increased exponentially as the canopy was gradually wetted, regardless of the radiation environment. This increase in TE results from Tc approaching zero while An maintains positive values. Overall, this study provides an integrated understanding of how fog alters M. faya functioning and, potentially, other cloud forest tree species.
How to describe a new species in zoology and avoid mistakes
Authors: Braby Michael F , Hsu Yu-Feng , Lamas Gerardo
Published: May 2024

Taxonomy is the science of discovering, naming, describing, diagnosing, identifying, and classifying different kinds of taxa, from species to families. It lays the foundation for all of the biological sciences. The rapid increase in both taxonomic descriptions and malpractice in recent decades indicates a need for consistency in the procedure and quality of taxonomic research publications dealing with recognition of new taxa, name changes, and nomenclatural acts. Indeed, there are numerous examples in the recent literature of taxonomic works that fall short of the basic procedures and minimum standards required for naming new species according to the mandatory provisions and recommendations of the International Code of Zoological Nomenclature, accepted standards of taxonomic best practice, and journal editorial policy. Here, we provide practical guidelines of the procedure and key elements required to name, describe, and publish a new animal species or revise the taxonomic status of a species. We then discuss some of the common pitfalls that should be avoided. Mistakes commonly made include failure to read the Code, to review the primary taxonomic literature, to examine type material, to construct the taxon name correctly, to explicitly establish the new taxon, to provide adequate typification, to clearly differentiate the new taxon, to register the publication of the new taxon name in ZooBank, or to publish the name of the new taxon in a manner that is compliant with the Code. We provide some examples of these mistakes, mainly from butterflies (Insecta: Lepidoptera: Papilionoidea) and, to some extent, reptiles because these taxon groups seem to have an unusually high level of poor taxonomic practice.
The effects of oxidative stress and intracellular calcium on mitochondrial permeability transition pore formation in equine spermatozoa
Authors: Gibb Zamira , Aitken Robert J. , Sheridan Alecia R. , Holt Brandan , Waugh Stephanie , Swegen Aleona
Published: May 2024

The in vitro storage of stallion spermatozoa for use in artificial insemination leads to oxidative stress and imbalances in calcium homeostasis that trigger the formation of the mitochondrial permeability transition pore (mPTP), resulting in premature cell death. However, little is understood about the dynamics and the role of mPTP formation in mammalian spermatozoa. Here, we identify an important role for mPTP in stallion sperm Ca2+ homeostasis. We show that stallion spermatozoa do not exhibit “classical” features of mPTP; specifically, they are resistant to cyclosporin A‐mediated inhibition of mPTP formation, and they do not require exogenous Ca2+ to form the mPTP. However, chelation of endogenous Ca2+ prevented mPTP formation, indicating a role for intracellular Ca2+ in this process. Furthermore, our findings suggest that this cell type can mobilize intracellular Ca2+ stores to form the mPTP in response to low Ca2+ environments and that under oxidative stress conditions, mPTP formation preceded a measurable increase in intracellular Ca2+, and vice versa. Contrary to previous work that identified mitochondrial membrane potential (MMP) as a proxy for mPTP formation, here we show that a loss of MMP can occur independently of mPTP formation, and thus MMP is not an appropriate proxy for the detection of mPTP formation. In conclusion, the mPTP plays a crucial role in maintaining Ca2+ and reactive oxygen species homeostasis in stallion spermatozoa, serving as an important regulatory mechanism for normal sperm function, thereby contraindicating the in vitro pharmacological inhibition of mPTP formation to enhance sperm longevity.