bluuebunny/crossref_metadata_2025 huggingface dataset:
A de novo nonsense variant in the DMD gene associated with X‐linked dystrophin‐deficient muscular dystrophy in a cat
Authors: Yokoyama Nozomu , Matsumoto Yuki , Yamaguchi Takahisa , Okada Kazuki , Kinoshita Ryohei , Shimbo Genya , Ukawa Hisashi , Ishii Ryuga , Nakamura Kensuke , Yamazaki Jumpei , Takiguchi Mitsuyoshi
Published: April 2024

Background

X‐linked dystrophin‐deficient muscular dystrophy (MD) is a form of MD caused by variants in the DMD gene. It is a fatal disease characterized by progressive weakness and degeneration of skeletal muscles.

Hypothesis/Objectives

Identify deleterious genetic variants in DMD by whole‐genome sequencing (WGS) using a next‐generation sequencer.

Animals

One MD‐affected cat, its parents, and 354 cats from a breeding colony.

Methods

We compared the WGS data of the affected cat with data available in the National Center for Biotechnology Information database and searched for candidate high‐impact variants by in silico analyses. Next, we confirmed the candidate variants by Sanger sequencing using samples from the parents and cats from the breeding colony. We used 2 genome assemblies, the standard felCat9 (from an Abyssinian cat) and the novel AnAms1.0 (from an American Shorthair cat), to evaluate genome assembly differences.

Results

We found 2 novel high‐impact variants: a 1‐bp deletion in felCat9 and an identical nonsense variant in felCat9 and AnAms1.0. Whole genome and Sanger sequencing validation showed that the deletion in felCat9 was a false positive because of misassembly. Among the 357 cats, the nonsense variant was only found in the affected cat, which indicated it was a de novo variant.

Conclusion and Clinical Importance

We identified a de novo variant in the affected cat and next‐generation sequencing‐based genotyping of the whole DMD gene was determined to be necessary for affected cats because the parents of the affected cat did not have the risk variant.
Prognostic indicators of outcome in nonambulatory beef cattle presented to 2 referral hospitals: A retrospective study of 63 cases
Authors: Perez‐Solano Diana , Reppert Emily J. , Stockler Jenna E. , Gaonkar Pankaj , Huber Laura , Passler Thomas , Bayne Jenna E. , Chamorro Manuel F.
Published: April 2024

Background

Down cow syndrome is commonly described in dairy cattle. The diagnosis and treatment of nonambulatory cattle is challenging and prognostic indicators of this condition in beef cattle have not been determined.

Objectives

Evaluate records of beef cattle (≥2 years of age) presented to 2 referral hospitals for inability to stand and identify prognostic indicators for survival to discharge.

Animals

Sixty‐three adult beef cattle treated for inability to stand at 2 referral hospitals.

Methods

Medical records of 63 beef cattle presented for inability to stand between January 2010 and December 2022 were retrospectively analyzed. Continuous and categorical variables were included in univariate and multivariate regression models to evaluate their association with outcome.

Results

Of 63 animals included in the study, 19% (12/63) were discharged, and the remaining 81% (n = 51) either died (11.1%) or were euthanized (69.8%). The odds of being discharged increased with each additional day of hospitalization (odds ratio [OR], 2.66; 95% confidence interval [CI], 1.39‐6.89) and with each additional flotation therapy session (OR, 2.108; 95% CI, 1.209‐4.219). Down beef cattle with a diagnosis of calving peripheral nerve paralysis and capable of walking out the tank after the first flotation session were 6.66 (95% CI, 1.58‐35.51) and 30 (95% CI, 4.4‐614.98) times more likely to be discharged compared with cattle that had other diagnoses and those that were unable to walk out the tank, respectively.

Conclusions and Clinical Importance

Treatment of nonambulatory beef cattle carries a poor prognosis. Practitioners can use information from our study as a guide for treatment or euthanasia decisions of nonambulatory beef cattle.
Between control and participation: The politics of algorithmic management
Authors: Krzywdzinski Martin , Schneiß Daniel , Sperling Andrea
Published: April 2024

Understanding the role of human management is crucial for the debate over algorithmic management—to date limited to studies on the platform economy. This qualitative case study in logistics reconstructs the actor constellations (managers, engineers, data scientists and workers) and negotiation processes in different phases of algorithmic management. It offers two major contributions to the literature: (1) a process model distinguishing three phases: goal formation, data production and data analysis, which is used to analyse (2) the politics of algorithmic management in conventional workplaces, which differ significantly from platform companies. The article goes beyond surveillance to elucidate the role of the regulatory framework, various actors' knowledge contributions to the algorithmic management system, and the power relations resulting therefrom. While the managerial goals in the examined case were not oriented towards a surveillance regime, the outcome was nevertheless a centralisation of knowledge and disempowerment of workers.
A Semi‐parametric Panel Data Model with Common Factors and Spatial Dependence
Authors: Soberon Alexandra , Musolesi Antonio , Rodriguez‐Poo Juan M.
Published: April 2024

Abstact

In the analysis of the Griliches' knowledge capital production function, previous works pointed out the relevance of incorporating slope heterogeneity in the technological parameters, cross‐sectional dependence arising simultaneously from common factors and spillovers, and possible nonlinear effects of relevant common observed variables. In order to solve the above problems, in this article we introduce a semi‐parametric model in a partially linear form that copes simultaneously with all the previous specification issues. The asymptotic properties of the resulting estimators are obtained and the theoretical findings are further supported for small samples via several Monte Carlo experiments and an empirical application.
Measuring outcomes when odontogenic sinusitis is treated with endoscopic sinus surgery: A systematic review
Authors: Bell Garmon , Howard Laura , Murphy Siofra , Pelekoudas Nikolaos
Published: April 2024

Aim

To determine outcome measurement when odontogenic sinusitis (ODS) is treated by Endoscopic Sinus Surgery (ESS).

Materials and Methods

A PRISMA compliant systematic review using MeSH headings on Pubmed, Ovid and Embase. Inclusion criteria: Adults with odontogenic maxillary sinus disease undergoing ESS. Exclusion criteria: Adolescents, odontogenic disease related to; trauma, neoplasia, tumour resection, palatal cleft or fungal infection, previous sinus surgery, endoscopic surgery not involving the middle meatus.

Results

A total of 1462 papers were identified, 68 eligible for review. No randomised controlled trials were identified. Twenty‐three papers (34%) reported a successful outcome as no disease at endoscopy and reduced sinonasal symptoms; 14 papers (21%) based outcomes on endoscopy, reduced symptoms and resolution of sinus opacification or reduced mucosal thickness; 1 paper established success on reduced symptoms only and 7 papers (10%) based outcomes on radiographic findings only. Other primary measures of success were excision and closure of oro‐antral fistula, 6 (9%), removal of odontogenic cysts, 5 (7%), removal of displaced dental implants, 4 (6%), removal of displaced root of tooth, 3 (4%). Five papers (7%) reported no outcome measure. Additional measures of outcome were; retention of dental implants perforating the sinus floor, survival of sinus floor grafting with subsequent implant placement and retention of teeth with persistent apical periodontitis.

Conclusion

Reported outcome measures were very heterogeneous. In consideration of the weak evidence base for the role of ESS in ODS management, more consistent measurement and reporting of patient symptoms, clinical and radiological signs with endoscopic findings is recommended to enable meta‐analysis.
Biliary strictures post pediatric liver transplantation—incidence and risk factors in a single tertiary referral transplant center
Authors: Vingrovich Odelia , Cooper Shiri , Gurevich Michael , Cohen Aenov , Mozer‐Glassberg Yael , Bar‐Lev Michal Rosenfeld , Shamir Raanan , Waisbourd‐Zinman Orith
Published: April 2024

Background

Biliary strictures are a significant cause of morbidity and graft loss in pediatric liver transplant recipients. Risk factors for the development of biliary strictures are not fully established. We aimed to evaluate the incidence of biliary strictures and treatment modalities outcomes and to identify potential risk factors for occurrence.

Methods

Pediatric patients who underwent liver transplantation in the single tertiary pediatric liver transplant center in Israel were evaluated. We compared demographics, presentation, laboratory results, imaging, treatment, and outcomes between patients with and without biliary stricture. Multivariate regression analyses were used to identify risk factors for biliary strictures.

Results

Among 121 pediatric liver transplant patients, 65 (53.7%) were males; the median age at the time of liver transplantation was 43 (3–215) months. Fifteen patients (12.4%) had biliary strictures following transplantation. One (7%) patient with biliary stricture was treated via endoscopic retrograde cholangiopancreatography, and 12 patients (80%) underwent interventions via a percutaneous transhepatic approach. Nine of the 12 patients were treated successfully, requiring one or multiple procedures, while the remaining had surgery or laser therapy. Risk factors for the development of biliary strictures were biliary leak, acute cellular rejection, and the presence of two biliary anastomoses.

Conclusions

In our cohort, the presence of two biliary anastomoses and post‐transplant complications including acute cellular rejection and early biliary leaks were associated with biliary strictures in pediatric liver transplantation recipients. Percutaneous transhepatic interventions result in good outcomes in most patients.
Enrollment and use of a peer counselor mHealth texting program to support breastfeeding in low‐income people: A pilot study in the District of Columbia
Authors: Robert Rebecca C. , Moody Nicole G. , Woody Emily , Kuehn Doris , Thompson Paulette , Roess Amira A.
Published: April 2024

Objective

To describe the characteristics of postpartum people who did and did not enroll in a breastfeeding peer‐counselor mobile health (mHealth) texting program as well as the issues raised through 2‐way texting with peer counselors.

Design

Pilot intervention study involving two Special Supplemental Nutrition Programs for Women Infants and Children (WIC) sites in the District of Columbia over 1 year.

Sample

WIC recipients.

Measurements

Descriptive statistics, comparison of recipients who enrolled or not and qualitative content analysis of text messages.

Intervention

A breastfeeding peer counselor texting program entitled BfedDC involving routine 1‐way programmed messages and 2‐way texting capacity for recipients to engage with peer counselors.

Results

Among our sample (n = 1642), nearly 90% initiated breastfeeding. A total of 18.5% (n = 304) enrolled in the BfedDC texting program, of whom 19.7% (n = 60) utilized the 2‐way texting feature. Message content covered seven content themes and included inquiries about expressing human milk, breastfeeding difficulties, breastfeeding frequency and duration, appointments and more.

Conclusions

Although enrollment was relatively low in BfedDC, benefits included 1‐way supportive texts for breastfeeding and the ability to 2‐way text with peer counselors. This program aligns with the Surgeon General's Call to Action to Support Breastfeeding and promotes breastfeeding equity in low‐income people.
The effect of environmental health education on microplastic pollution awareness
Authors: Ahmet Miraç Bayoğlu , Fatoş Uncu
Published: April 2024

Objective

The aim of this research is to investigate the effect of environmental health education given at the ninth‐grade level on the microplastic pollution awareness level of students.

Methods

This pretest‐posttest experimental study with a randomized control group was conducted between 2022 and 2023 in three high schools in a province in eastern Turkey. The sample of the study consisted of 90 ninth‐grade students (experimental group: 45, control group: 45), and the sample magnitude was determined by power analysis. Tools such as the “Personal Information Form” and “Microplastic Pollution Awareness Scale (MPAS)” were used to collect data. Training was given to the experimental group as a nursing intervention in a total of four sessions at 15‐day intervals. No intervention was applied to the individuals in the control group.

Results

While no significant difference was observed in the MPAS total score in the control group according to the pretest and posttest mean scores, a significant difference was observed in the MPAS total score in the experimental group (p < 0.05). When the posttest mean scores of the experimental and control groups were examined, it was observed that the posttest mean scores of the experimental group were higher than the posttest mean scores of the control group and there was a statistically significant difference (p < 0.05).

Conclusion

It was observed that the microplastic pollution awareness level of the experimental group students who received environmental health training increased significantly. The issue of environmental health should be integrated into the education curriculum in schools and students' awareness levels should be increased.
Ergot of cereals: Toxins, pathogens and management
Authors: Berraies Samia , Liu Miao , Menzies James G. , Tittlemier Sheryl A. , Overy David P. , Walkowiak Sean
Published: April 2024

Ergot is a fungal disease of many plants but is perhaps most commonly associated with domesticated grasses or cereals, such as rye, wheat, barley, oat, sorghum, millet, maize and rice. Ergot is of historical significance, having been reported for several millennia, but is also of concern in modern agricultural production systems. Caused by many different species within the genus Claviceps, the fungi cause the production of sclerotia, which are typically dark in colour, in place of healthy grain. The sclerotia contain toxins that can make the grain unsafe for consumption by humans or livestock. Ergot can be managed both preharvest as well as postharvest to minimize the presence of sclerotia and their associated toxins in food and feed systems. In this review, we provide a detailed update on our current knowledge of ergot on cereals, with a focus on recent advances in our understanding of fungal toxins and their regulation, pathogen biology and disease management.
Hunting for sources of durable resistance in crop cultivar evaluation data: The case of wheat yellow rust in France
Authors: Vidal Tiphaine , Perronne Rémi , Boixel Anne‐Lise , du Cheyron Philippe , Dubs Florence , Enjalbert Jérôme
Published: April 2024

Cultivar resistance is a major asset for the management of crop diseases and can play an important role in agroecological transition. However, the wide deployment of a reduced number of resistance genes can lead to a rapid adaptation of pathogen populations and to a loss of resistance efficiency. The objective of this study was to characterize and discuss different trajectories of adult plant ratings for resistance to yellow rust in French wheat cultivars between 1963 and 2018. Among 719 cultivars assessed for at least 2 years, 590 cultivars showed no variation in their resistance scores, despite a mean of 4.3 years and up to 33 years of assessment. A set of descriptive variables was computed in order to compare the evolution of resistance score of 129 cultivars that experienced resistance variation. We applied a principal component analysis and a hierarchical clustering on principal components to this subdataset to constitute clusters corresponding to different cultivar profiles. Clusters C1 and C2 had small resistance variations (1–2 points on a 1–9 scale); Cluster C3 had long assessment durations and several small drops in resistance score and could be associated with quantitative resistance erosion; Cluster C4 included major drops in resistance score (4–5 points), often associated with known breakdowns of major resistance genes. Cases of limited drops in resistance score as a known resistance gene was broken down suggest the presence of efficient adult plant resistance. We discuss the use of information extracted from this dataset and methods to further explore sources of resistance to yellow rust present in French cultivars.
Connecting founding and dissolution: A demographic study of the US nonprofit sector
Authors: Mayer Duncan J.
Published: April 2024

Despite a rich literature on nonprofit density, the founding and dissolution of nonprofit organizations remains poorly understood. This study explores the founding and dissolution in nonprofit populations including density dependence, resource concentration, government size, and hypothesizes that dissolution creates an entrepreneurial opportunity. The hypotheses are tested using county level data covering the continental US from 2010 to 2016 (N = 21,756). The results show government size, competition, and resource concentration are important for understanding founding and dissolution, and establishes strong support for a link between the events: a one standard deviation increase in the number of dissolutions in a county predicts an increase of 1.5% (CI: .72–2.31) in the nonprofit founding rate. The study highlights ways for public officials to support nonprofit entrepreneurship and calls for renewed interest in ecological applications in contemporary nonprofit populations.
Expression pattern of germ cell markers in cryptorchid stallion testes
Authors: Shakeel Muhammad , Choi Younju , Yoon Minjung
Published: April 2024

Cryptorchidism affects spermatogenesis and testis development, often resulting in stallion subfertility/infertility. This study aims to identify the specific germ cells impacted by cryptorchism in stallions. In a previous study, we found that PGP9.5 and VASA are molecular markers expressed in different germ cells within stallions. Herein, we assessed the heat stress‐induced response of spermatogonial stem cells (SSCs) in the seminiferous tubules (ST) of cryptorchid stallion testes (CST) and normal stallion testes (NST). This goal was accomplished by comparing PGP9.5 and VASA expression patterns through reverse transcription quantitative PCR and immunofluorescence assays. We also compared the cross‐sectional ST area between groups. Six post‐pubertal Thoroughbred unilateral cryptorchid stallions were used. The relative abundance of the mRNA transcripts of PGP9.5 and VASA was significantly upregulated in the NST group than in the CST group. Additionally, the cross‐sectional ST area and localization of PGP9.5 and VASA in germ cells were significantly higher in the NST group than in the CST group. Regarding Leydig cells, PGP9.5 staining was observed in both groups. Spermatogonia, primary spermatocytes and secondary spermatocytes were immunostained with VASA in the NST group, while immunostaining was only observed in spermatogonia in the CST group. These results indicate long‐term exposure to heat stress conditions, such as cryptorchidism, directly impacts germ cell proliferation and differentiation, leading to impaired spermatogenesis and compromised fertility in stallions.
A comparative study of the judicial construction of scientific credibility in climate litigation
Authors: Zhu Mingzhe , Fan Liyuan
Published: April 2024

Although the value of climate science in the courtroom is widely acknowledged, few studies have evaluated how judges achieve a scientifically sound grounding for their rulings. Drawing insights from legal culture and science and technology studies, we compare the determination of scientific credibility in leading climate cases in Europe and the United States. Judges on both sides of the Atlantic answer similar questions about scientific facts and commonly use authoritative reports and testimonies from qualified experts. However, while judges in the Netherlands, France and Germany find value in the political mandates of international or national bodies that generate scientific reports, American judges seek to keep scientific expertise from the influence of policy considerations. We make sense of this difference by identifying two competing ideals of expertise, namely the ‘view of everyone’ ideal in Europe and the ‘view from nowhere’ ideal in the United States. Although climate science is often articulated in universalist terms, the cultural embeddedness of adjudication means that the evaluation of credibility varies by jurisdiction.
Epidemiology, etiology and prevention of injuries in competitive ice speed skating—limited current evidence, multiple future priorities: A scoping review
Authors: Hendricks Matthias , Verhagen Evert , van de Water Alexander T. M.
Published: April 2024

Long‐track and short‐track ice speed skating are integral to the Winter Olympics. The state of evidence‐based injury prevention in these sports is unclear. Our goals were to summarize the current scientific knowledge, to determine the state of research, and to highlight future research areas for injury prevention in ice speed skating. We conducted a scoping review, searching all injury and injury prevention studies in competitive ice speed skaters. The six‐stage Translating Research into Injury Prevention Practice (TRIPP) framework summarized the findings. The systematic search yielded 1109 citations. Nineteen studies were included, and additional searches yielded another 13 studies, but few had high‐quality design. TRIPP stage 1 studies (n = 24) found competition injury rates from 2% to 18% of participants with various injury locations and types. Seasonal prevalence of physical complaints was up to 84% (for back pain) in long‐ and short‐track. Ten studies covered information on TRIPP stage 2, with two small etiological studies linking injuries to functional strength deficits (short‐track) and training load (long‐track). Questionnaire studies identified various perceived risk factors for injuries but lacked further scientific evidence. Most TRIPP stage 3 studies (five out of eight) focused on developing protective measures, while two studies found short‐track helmets performed poorly compared to helmets used in other sports. No study evaluated the efficacy, the intervention context, or the effectiveness (TRIPP stages 4–6) of the measures. Scientific knowledge on injury prevention in ice speed skating is limited. Future research should prioritize high‐quality studies on injury epidemiology and etiology in the sports.
First international consensus statement on sports psychiatry
Authors: Claussen Malte Christian , Currie Alan , Koh Boon Yau Eugene , Nishida Masaki , Martínez Vania , Burger James , Creado Shane , Schorb Alexander , Nicola Roberto Fernandes , Pattojoshi Amrit , Menon Ranjit , Glick Ira , Whitehead Jim , Edwards Carla , Baron David
Published: April 2024

Sports psychiatry is a young field of medicine and psychiatry that focuses on mental health among athletes, and sports and exercise within psychiatry and mental disorders. However, the development of sports psychiatry and its fields of activity vary from region to region and are not uniform yet. Sports psychiatry and the role of sports psychiatrists have also already been discussed in the field of sports and exercise medicine, and within medical teams in competitive and elite sports. A uniform definition on sports psychiatry, its fields of activity, sports psychiatrist, and the essential knowledge, skills, and abilities (plus attitudes, eKSA+A) of the sports psychiatrist were developed as part of an International Society for Sports Psychiatry (ISSP) Summit, as well as First International Consensus Statement on Sports Psychiatry. Three fields of activity can be distinguished within sports psychiatry: (i) mental health and disorders in competitive and elite sports, (ii) sports and exercise in prevention of and treatment for mental disorders, and (iii) mental health and sport‐specific mental disorders in recreational sports. Each of these fields have its own eKSA+A. The definitions on sports psychiatry and sports psychiatrists, as well as the framework of eKSA+A in the different fields of activity of sports psychiatrists will help to unify and standardize the future development of sports psychiatry, establish a standard of service within sports psychiatry and together with the neighboring disciplines, and should be included into current, and future sports psychiatry education and training.
A critical review of sociological research on sexual pleasure
Authors: Regan Hannah
Published: April 2024

Sociologists of sexuality often invoke the theme of pleasure, but it is not always clear what scholars believe the implications and importance of pleasure are. To this end, this paper reviews the existing literature on sexual pleasure, specifically within the field of sociology, to demonstrate what questions about sexual pleasure are (and are not) currently being asked. Through a systematic literature review, I demonstrate that scholars often lack a justification for why pleasure is important. I also connect themes between the kind of questions being asked about pleasure and the justifications attached to these studies, relating to risk mitigation, relationship satisfaction and well‐being, power structures, and moral oversight. Based on this review, I make recommendations for the future of sexual pleasure research with the goal of centering pleasure for pleasure's sake and embracing its liberatory possibilities.
Labour market gender gaps and childcare policies in countries with different social investment strategies
Authors: Chłoń‐Domińczak Agnieszka , Kotowska Irena E. , Magda Iga , Smyk‐Szymańska Magdalena , Strzelecki Paweł , Bolesta Karolina
Published: April 2024

We study the role of formal and informal childcare within the ECEC policies for gender employment and pay gaps, considering the life course stages distinctive for childcare tasks. The ECEC policies are framed within the types of social investment strategies identified in the EU countries to picture developments in social investments after 2005. The aggregated EU‐SILC data from 2005 to 2019 for 27 European countries have been used in the panel regression models to uncover how the caring arrangements influence labour market gendered outcomes of women at different ages (15–24, 25–49, 50–65). We find that better provision and use of early education and childcare not only contribute to early investment in human capital but it also facilitates mothers' employment and thus contributes to lowering gender employment and pay gaps. However, better coverage of care for children older than 3 years old results in negative employment effects for grandmothers. These effects vary also across countries, depending on their overall institutional setting depicted by the types of social investment strategies distinguished. Consequently, the ECEC agenda should be extended by addressing the employment of women at the pre‐retirement age. It is crucial not only for reducing gender gap in employment and pay but also in the light of challenges generated by demographic developments—the labour force shrinking and the population ageing processes.
Along‐strike variation of fault slip rate of a transform plate boundary in Tierra del Fuego (South Patagonia)
Authors: Vassallo Riccardo , Martinod Joseph , Roy Sandrine , Sue Christian , Astrade Laurent
Published: April 2024

The Magallanes–Fagnano Fault is an active strike‐slip structure accommodating the relative displacement between South America and the Scotia Plate. The Chilean portion of the fault is poorly studied because most of it runs below the sea level in the Strait of Magellan. Our tectonic geomorphological study is focused on a rare onshore fault section, along which streams horizontally deflected by hundreds of metres since the last main deglaciation are compatible with a dominant left‐lateral fault kinematics and yield a slip rate of 15.7 ± 2.4 mm/year. This rate is between 2 and 3 times higher than the one estimated on the Argentinian portion of the fault over the same period. This spatial variation may be due to both glacial unloading on the fault zone and/or structural factors. These results point out the need to study strike‐slip faults on several portions to unravel behaviour changes related to internal or external forcing.
Integrating multi‐omics data reveals energy and stress signaling activated by abscisic acid in Arabidopsis
Authors: Yoshida Takuya , Mergner Julia , Yang Zhenyu , Liu Jinghui , Kuster Bernhard , Fernie Alisdair R. , Grill Erwin
Published: April 2024

Phytohormones are essential signaling molecules regulating various processes in growth, development, and stress responses. Genetic and molecular studies, especially using Arabidopsis thaliana (Arabidopsis), have discovered many important players involved in hormone perception, signal transduction, transport, and metabolism. Phytohormone signaling pathways are extensively interconnected with other endogenous and environmental stimuli. However, our knowledge of the huge and complex molecular network governed by a hormone remains limited. Here we report a global overview of downstream events of an abscisic acid (ABA) receptor, REGULATORY COMPONENTS OF ABA RECEPTOR (RCAR) 6 (also known as PYRABACTIN RESISTANCE 1 [PYR1]‐LIKE [PYL] 12), by integrating phosphoproteomic, proteomic and metabolite profiles. Our data suggest that the RCAR6 overexpression constitutively decreases the protein levels of its coreceptors, namely clade A protein phosphatases of type 2C, and activates sucrose non‐fermenting‐1 (SNF1)‐related protein kinase 1 (SnRK1) and SnRK2, the central regulators of energy and ABA signaling pathways. Furthermore, several enzymes in sugar metabolism were differentially phosphorylated and expressed in the RCAR6 line, and the metabolite profile revealed altered accumulations of several organic acids and amino acids. These results indicate that energy‐ and water‐saving mechanisms mediated by the SnRK1 and SnRK2 kinases, respectively, are under the control of the ABA receptor‐coreceptor complexes.
Linear isometries of noncommutative L0$L_0$‐spaces
Authors: Ber Aleksey , Huang Jinghao , Sukochev Fedor
Published: April 2024

The description of (commutative and noncommutative) ‐isometries has been studied thoroughly since the seminal work of Banach. In the present paper, we provide a complete description for the limiting case, isometries on noncommutative ‐spaces, which extends the Banach–Stone theorem and Kadison's theorem for isometries of von Neumann algebras. The result is new even in the commutative setting.
Development of an enhanced scoring system to predict ICU readmission or in-hospital death within 24 hours using routine patient data from two NHS Foundation Trusts
Authors: Pimentel Marco A F , Johnson Alistair , Darbyshire Julie Lorraine , Tarassenko Lionel , Clifton David A , Walden Andrew , Rechner Ian , Watkinson Peter J , Young J Duncan
Published: April 2024

Rationale

Intensive care units (ICUs) admit the most severely ill patients. Once these patients are discharged from the ICU to a step-down ward, they continue to have their vital signs monitored by nursing staff, with Early Warning Score (EWS) systems being used to identify those at risk of deterioration.

Objectives

We report the development and validation of an enhanced continuous scoring system for predicting adverse events, which combines vital signs measured routinely on acute care wards (as used by most EWS systems) with a risk score of a future adverse event calculated on discharge from the ICU.

Design

A modified Delphi process identified candidate variables commonly available in electronic records as the basis for a ‘static’ score of the patient’s condition immediately after discharge from the ICU. L1-regularised logistic regression was used to estimate the in-hospital risk of future adverse event. We then constructed a model of physiological normality using vital sign data from the day of hospital discharge. This is combined with the static score and used continuously to quantify and update the patient’s risk of deterioration throughout their hospital stay.

Setting

Data from two National Health Service Foundation Trusts (UK) were used to develop and (externally) validate the model.

Participants

A total of 12 394 vital sign measurements were acquired from 273 patients after ICU discharge for the development set, and 4831 from 136 patients in the validation cohort.

Results

Outcome validation of our model yielded an area under the receiver operating characteristic curve of 0.724 for predicting ICU readmission or in-hospital death within 24 hours. It showed an improved performance with respect to other competitive risk scoring systems, including the National EWS (0.653).

Conclusions

We showed that a scoring system incorporating data from a patient’s stay in the ICU has better performance than commonly used EWS systems based on vital signs alone.

Trial registration number

ISRCTN32008295.
Impact of health education on promoting influenza vaccination health literacy in primary school students: a cluster randomised controlled trial protocol
Authors: Xie Weiguang , Xiao Jingyi , Chen Jingyi , Huang Anzhong , Huang Xuehua , He Shaoyi , Xu Lin
Published: April 2024

Introduction

Influenza is a major public health threat, and vaccination is the most effective prevention method. However, vaccination coverage remains suboptimal. Low health literacy regarding influenza vaccination may contribute to vaccine hesitancy. This study aims to evaluate the effect of health education interventions on influenza vaccination rates and health literacy.

Methods and analysis

This cluster randomised controlled trial will enrol 3036 students in grades 4–5 from 20 primary schools in Dongguan City, China. Schools will be randomised to an intervention group receiving influenza vaccination health education or a control group receiving routine health education. The primary outcome is the influenza vaccination rate. Secondary outcomes include health literacy levels, influenza diagnosis rate, influenza-like illness incidence and vaccine protection rate. Data will be collected through questionnaires, influenza surveillance and self-reports at baseline and study conclusion.

Ethics and dissemination

Ethical approval has been sought from the Ethics Committee of the School of Public Health, Sun Yat-sen University. Findings from the study will be made accessible to both peer-reviewed journals and key stakeholders.

Trial registration number

NCT06048406.
Red filter meibography by smartphones in patients with meibomian gland dysfunction: a validity and reliability study
Authors: Anissa Gisela Haza , La Distia Nora Rina , Widyawati Syska , Sitompul Ratna , Yusuf Prasandhya Astagiri , Kekalih Aria
Published: April 2024

Objective

The objective of this study is to determine the validity and reliability of the red filter meibography by smartphone compared with infrared in assessing meibomian gland drop-out.

Methods and analysis

An analytical cross-sectional study was done with a total of 35 subjects (68 eyes) with suspected MGD based on symptoms and lid morphological abnormalities. Meibomian glands were photographed using two smartphones (Samsung S9 and iPhone XR) on a slit-lamp with added red filter. Images were assessed subjectively using meiboscore by the two raters and drop-out percentages were assessed by ImageJ.

Results

There was no agreement in meiboscore and a minimal level of agreement in drop-out percentages between red filter meibography and infrared. Inter-rater reliability showed no agreement between two raters. Intra-rater reliability demonstrated weak agreement in rater 1 and no agreement in rater 2.

Conclusion

Validity of the red filter meibography technique by smartphones is not yet satisfactory in evaluating drop-out. Further improvement on qualities of images must be done and research on subjective assessment was deemed necessary due to poor results of intrarater and inter-rater reliability.
Armored TGFβRIIDN ROR1-CAR T cells reject solid tumors and resist suppression by constitutively-expressed and treatment-induced TGFβ1
Authors: Tran Tri Minh , Chand Thakuri Bal Krishna , Nurmukhambetova Saule , Lee Jia-Jye , Hu Peirong , Tran Ngoc Q , Steimle Brittany , Dash Pradyot , Schneider Dina
Published: April 2024

Background

Chimeric antigen receptor (CAR) T-cell therapy target receptor tyrosine kinase-like orphan receptor 1 (ROR1) is broadly expressed in hematologic and solid tumors, however clinically-characterized ROR1-CAR T cells with single chain variable fragment (scFv)-R12 targeting domain failed to induce durable remissions, in part due to the immunosuppressive tumor microenvironment (TME). Herein, we describe the development of an improved ROR1-CAR with a novel, fully human scFv9 targeting domain, and augmented with TGFβRIIDN armor protective against a major TME factor, transforming growth factor beta (TGFβ).

Methods

CAR T cells were generated by lentiviral transduction of enriched CD4+and CD8+T cells, and the novel scFv9-based ROR1-CAR-1 was compared with the clinically-characterized ROR1-R12-scFv-based CAR-2 in vitro and in vivo.

Results

CAR-1 T cells exhibited greater CAR surface density than CAR-2 when normalized for %CAR+, and produced more interferon (IFN)-γ tumor necrosis factor (TNF)-α and interleukin (IL)-2 in response to hematologic (Jeko-1, RPMI-8226) and solid (OVCAR-3, Capan-2, NCI-H226) tumor cell lines in vitro. In vivo, CAR-1 and CAR-2 both cleared hematologic Jeko-1 lymphoma xenografts, however only CAR-1 fully rejected ovarian solid OVCAR-3 tumors, concordantly with greater expansion of CD8+and CD4+CAR T cells, and enrichment for central and effector memory phenotype. When equipped with TGFβ-protective armor TGFβRIIDN, CAR-1 T cells resisted TGFβ-mediated pSmad2/3 phosphorylation, as compared with CAR-1 alone. When co-cultured with ROR-1+AsPC-1 pancreatic cancer line in the presence of TGFβ1, armored CAR-1 demonstrated improved recovery of killing function, IFN-γ, TNF-α and IL-2 secretion. In mouse AsPC-1 pancreatic tumor xenografts overexpressing TGFβ1, armored CAR-1, in contrast to CAR-1 alone, achieved complete tumor remissions, and yielded accelerated expansion of CAR+T cells, diminished circulating active TGFβ1, and no apparent toxicity or weight loss. Unexpectedly, in AsPC-1 xenografts without TGFβ overexpression, TGFβ1 production was specifically induced by ROR-1-CAR T cells interaction with ROR-1 positive tumor cells, and the TGFβRIIDN armor conferred accelerated tumor clearance.

Conclusions

The novel fully human TGFßRIIDN-armored ROR1-CAR-1 T cells are highly potent against ROR1-positive tumors, and withstand the inhibitory effects of TGFß in solid TME. Moreover, TGFβ1 induction represents a novel, CAR-induced checkpoint in the solid TME, which can be circumvented by co-expressing the TGβRIIDN armor on T cells.
Risk of extended major adverse cardiovascular event endpoints with tofacitinib versus TNF inhibitors in patients with rheumatoid arthritis: a post hoc analysis of a phase 3b/4 randomised safety study
Authors: Buch Maya H , Bhatt Deepak L , Charles-Schoeman Christina , Giles Jon T , Mikuls Ted , Koch Gary G , Ytterberg Steven , Nagy Edward , Jo Hyejin , Kwok Kenneth , Connell Carol A , Masri Karim Richard , Yndestad Arne
Published: April 2024

Objectives

Compare the risk of extended major adverse cardiovascular (CV) event (MACE) composite outcomes and component events in patients with rheumatoid arthritis (RA) treated with tofacitinib versus tumour necrosis factor inhibitors (TNFi) in Oral Rheumatoid Arthritis Trial (ORAL) Surveillance.

Methods

Patients with RA aged ≥50 years and with ≥1 additional CV risk factor received tofacitinib 5 mg or 10 mg two times per day or TNFi. MACE (non-fatal myocardial infarction (MI), non-fatal stroke or CV death (MACE-3)) was extended by sequential addition of CV events (hospitalisation for unstable angina (MACE-4), coronary revascularisation (MACE-5), transient ischaemic attack (MACE-6), peripheral vascular disease (MACE-7)), heart failure (HF) hospitalisation (MACE-8) and venous thromboembolism (VTE; (MACE-8 plus VTE)). HRs (tofacitinib vs TNFi) were evaluated for MACE and individual components.

Results

HRs for MACE-4 to MACE-8 with combined and individual tofacitinib doses versus TNFi were similar. Risk of MACE-8 plus VTE appeared similar with tofacitinib 5 mg two times per day versus TNFi (HR 1.12 (0.82 to 1.52)), but higher with tofacitinib 10 mg two times per day versus TNFi (HR 1.38 (1.02 to 1.85)). Risk of MI was higher with tofacitinib versus TNFi, but difference in risk of other individual CV events was not suggested. Across extended MACE definitions, risk appeared higher with tofacitinib versus TNFi in those with atherosclerotic CV disease or age ≥65 years.

Conclusion

In ORAL Surveillance, risk of composite CV endpoints combining all ischaemic CV events and HF did not appear different with tofacitinib versus TNFi. The totality of CV risk was higher with tofacitinib 10 mg two times per day versus TNFi, driven by an increase in VTE.

Trial registration number

NCT02092467.
Comparison of active tuberculosis occurrence associated with Janus kinase inhibitors and biological DMARDs in rheumatoid arthritis
Authors: Song Yun-Kyoung , Lee Jaehee , Jo Junwoo , Kwon Jin-Won
Published: April 2024

Objectives

This study aimed to evaluate the risk of tuberculosis associated with the use of Janus kinase (JAK) inhibitors or biological disease-modifying antirheumatic drugs (bDMARDs) in patients diagnosed with rheumatoid arthritis (RA) in South Korea.

Methods

In this nationwide matched-cohort study, we retrospectively identified adult patients with new-onset RA from the National Health Insurance Service database who were prescribed bDMARDs or JAK inhibitors and recently underwent latent tuberculosis infection (LTBI) screening during 2012‒2021, and followed them up until the end of 2022 for the development of active tuberculosis. HRs were estimated using Cox proportional hazards regression in a propensity score-matched cohort.

Results

Among 16 760 matched patients with RA (3352 JAK inhibitor users and 13 408 bDMARD users), 18.8% received tuberculosis preventive therapy for LTBI. Overall, JAK inhibitor users had a significantly lower risk of tuberculosis than bDMARD users (HR (95% CI)=0.37 (0.22 to 0.62)). Among the patients treated for LTBI, patients with low treatment adherence had a significantly higher risk than those without LTBI (HR (95% CI)=2.78 (1.74 to 4.44)). Patients without LTBI and using JAK inhibitors had a significantly lower risk of tuberculosis across all ages and sexes compared with bDMARD users.

Conclusion

Patients with RA using JAK inhibitors have a significantly lower risk of active tuberculosis than bDMARD users in South Korea; however, patients with RA having LTBI are equally at risk regardless of the treatment received (JAK inhibitor vs bDMARD). Therefore, vigilant tuberculosis monitoring, especially in patients with low adherence to tuberculosis preventive therapy, is essential.
Analysis of belimumab prescription and outcomes in a 10-year monocentric cohort: is there an advantage with early use?
Authors: Tani Chiara , Zucchi Dina , Cardelli Chiara , Elefante Elena , Signorini Viola , Schilirò Davide , Cascarano Giancarlo , Gualtieri Luca , Valevich Anastasiya , Puccetti Giulia , Carli Linda , Stagnaro Chiara , Mosca Marta
Published: April 2024

Objective

The objective is to evaluate perscriptions of belimumab (BEL), how these have changed over the years and their impact on clinical outcomes in patients with systemic lupus erythematosus (SLE).

Methods

This is a retrospective analysis of prospectively collected data. We retrieved demographic and clinical data and concomitant therapies at BEL starting (baseline). Disease activity was assessed at baseline and after 6 and 12 months and organ damage at baseline and at the last visit.

Results

From 422 patients followed in the Pisa SLE cohort, 102 patients received BEL and were included and 22 (21.6%) were immunosuppressant (IS)-naïve. Lupus Low Disease Activity State (LLDAS) with a glucocorticoid (GC) dosage ≤5 mg/day (LLDAS5) and remission were achieved by 47% and 38% of patients at 6 months, and by 75% and 66% at 12 months. Comparing IS-naïve patients with those who received BEL after at least one conventional IS, we did not find significant differences in baseline characteristics and in the achievement of LLDAS5 and remission. Despite at baseline we did not observe significant differences in mean GC daily dosage, IS-naïve patients were taking a significantly lower GC daily dose at 6 and 12 months. Interestingly, IS-naïve patients were more common in the most recent years.

Conclusions

Our data confirm that BEL is effective in controlling disease activity, and in recent years BEL has been considered as an earlier treatment option before other IS. Early introduction of BEL can be at least as effective as a step-up approach and can help to reduce the GC dosage.
Understanding the psychosocial determinants of effective disease management in rheumatoid arthritis to prevent persistently active disease: a qualitative study
Authors: Stoll Nkasi , Dey Mrinalini , Norton Sam , Adas Maryam , Bosworth Ailsa , Buch Maya H , Cope Andrew , Lempp Heidi , Galloway James , Nikiphorou Elena
Published: April 2024

Background

According to epidemiological studies, psychosocial factors are known to be associated with disease activity, physical activity, pain, functioning, treatment help-seeking, treatment waiting times and mortality in people with rheumatoid arthritis (RA). Limited qualitative inquiry into the psychosocial factors that add to RA disease burden and potential synergistic interactions with biological parameters makes it difficult to understand patients’ perspectives from the existing literature.

Aim

This study aimed to gather in-depth patient perspectives on psychosocial determinants that drive persistently active disease in RA, to help guide optimal patient care.

Methods

Patient research partners collaborated on the research design and materials. Semistructured interviews and focus groups were conducted online (in 2021) with patients purposively sampled from diverse ethnicities, primary languages, employment status and occupations. Data were analysed using inductive thematic analysis.

Results

45 patients participated across 28 semistructured interviews and three focus groups. Six main themes on psychosocial determinants that may impact RA management were identified: (1) healthcare systems experiences, (2) patient education and health literacy, (3) employment and working conditions, (4) social and familial support, (5) socioeconomic (dis)advantages, and (6) life experiences and well-being practices.

Conclusion

This study emphasises the importance of clinicians working closely with patients and taking a holistic approach to care that incorporates psychosocial factors into assessments, treatment plans and resources. There is an unmet need to understand the relationships between interconnected biopsychosocial factors, and how these may impact on RA management.