bluuebunny/crossref_metadata_2025 huggingface dataset:
History and Limitations of the Traditional System for Resolving Investment Disputes
Authors: Dugan Christopher F , Wallace Jr , Rubins Noah , Sabahi Borzu
Published: August 2024

This chapter begins with a discussion of the harms suffered by foreign investors and the barriers to recovery by foreign investors. It then discusses the traditional remedies for foreign investors, some early investment protection regimens, and the limitations of historic dispute resolution processes.
Procedural Law Applicable in Investor-State Arbitration
Authors: Dugan Christopher F , Wallace Jr , Rubins Noah , Sabahi Borzu
Published: August 2024

An important and often overlooked issue in investment treaty arbitration concerns the determination of the system of law governing procedural aspects of the arbitration. The nationality of the law governing arbitral procedure may well differ from that applicable to the merits of the dispute, which is most often subject to some combination of international law and the law of the host state. The chapter discusses the different issues of applicable procedural law that may arise in non-ICSID arbitration proceedings. It then examines the same questions in the context of the ICSID Convention.
The Course of an Investment Arbitration
Authors: Dugan Christopher F , Wallace Jr , Rubins Noah , Sabahi Borzu
Published: August 2024

Investment arbitrations resemble commercial arbitrations in many ways but are dramatically different in others. The presence of a sovereign state in every such dispute can transform the tone and nature of an investment dispute. Tribunals are sometimes more solicitous of the position of a sovereign than they would be of a private party, if only because of the public policy and other noncommercial issues that often arise in investment disputes. This chapter describes the course of an investment arbitration and attempts to identify some of these similarities and differences.
Enforcement of Awards
Authors: Dugan Christopher F , Wallace Jr , Rubins Noah , Sabahi Borzu
Published: August 2024

This chapter discusses the enforcement of arbitration awards. Topics covered include confirmation, enforcement of awards under the New York Convention, execution in investment arbitrations, and sovereign immunity and the Washington Convention. It argues that enforcing an investment treaty arbitration award against a recalcitrant state may be the most difficult, lengthy, and expensive phase of an investor-state arbitration. In recent years, some nations have sought to restrict or rescind their participation in the investor-state treaty regime. Such attempts would make the enforcement process even more problematic.
After eco-theocide: the shift from ecological conservation to eco-theological conversation in Amitav Ghosh’s The Living Mountain
Authors: Panda Arnab , Mukhopadhyay Anway
Published: August 2024

Challenging the ontological dualism of being and thing, the article underscores the constant movement of “energy” between these two categories by reading Amitav Ghosh’s The Living Mountain within the paradigms of New Materialism, Shakta-Tantra and an eco-theological conceptualization of “energy”. Drawing on several post-secular philosophical ideas like “ecosophy” and “cosmotheandric spirituality”, it explores the alternative, Indigenous modes of communication with and through the divine Earth, which were gradually destroyed by seductive capitalism, resulting in eco-theocide and environmental disaster. This mode of eco-theological conversation with “material” nature diverges from the discourse of sustainable “conservation” used by late capitalism to underplay the history of ecological injustice. Finally, this article also plans to situate Ghosh’s The Living Mountain within the living traditions of mountain worship prevalent in different parts of India.
Characterizing Symptom Profiles in a Military Outpatient Cohort With COVID-19 in the Île-de-France Region
Authors: Bertron Emilie , Doutrelon Caroline , Etchegoyen Gabriel , Gislot Charlotte , Clausse Odile , Verret Catherine , Coste Sébastien , Josnard Justine
Published: August 2024

Introduction

The emergence of coronavirus disease 2019 (COVID-19) pandemic, driven by severe acute respiratory syndrome coronavirus 2, precipitated an unprecedented public health crisis, necessitating comprehensive response worldwide. The Ile-De-France region has been particularly affected, leading to rapid health care system strain and hospital saturation. Within this context, the 1st Armed Forces Medical Centre swiftly adapted its primary care services to cater to the unique needs of military personnel, leveraging telemedicine technologies for efficient health care delivery.

Materials and Methods

This study undertook an observational retrospective analysis to characterize the epidemiological profile of soldiers seeking outpatient care for non-severe COVID-19 symptoms at the 1st Armed Forces Medical Centre’s sub-centers between March and December 2020. Electronic medical records of patients were scrutinized to discern patterns in symptom presentation and evolution over time.

Results

The cross-section sample consisted of 519 patients, predominantly males (71%), with an average age of 38 years. Predominant symptoms reported were asthenia (43%), cephalalgia (41%), myalgia (40%), pyrexia (38%), and tussis (33%). A significant proportion of patients (33%) were asymptomatic at the follow-up consultations, marking a notable increase from initial assessments (14%). Although symptoms indicative of flu-like syndrome and sore throat exhibited regression between consultations, certain manifestations, such as anosmia, ageusia, and dyspnea, persisted without significant variance. Our analysis delineated five distinct symptom profiles within the cohort.

Conclusions

This study provides valuable insights into the clinical course of non-severe COVID-19 cases among military personnel receiving outpatient care, delineating five distinct symptom profiles. This complexity underscores the challenges in predicting and managing symptomatology effectively. Our findings align with existing literature but offer a unique perspective on military cohorts. Notably, in confined military settings with predominantly young and healthy individuals, symptomatic presentations tend to be milder. Robust public health interventions, including quarantine and contact tracing, are crucial to maintaining operational readiness amidst the pandemic’s challenges.
An integrated machine-learning model to predict nucleosome architecture
Authors: Sala Alba , Labrador Mireia , Buitrago Diana , De Jorge Pau , Battistini Federica , Heath Isabelle Brun , Orozco Modesto
Published: August 2024

We demonstrate that nucleosomes placed in the gene body can be accurately located from signal decay theory assuming two emitters located at the beginning and at the end of genes. These generated wave signals can be in phase (leading to well defined nucleosome arrays) or in antiphase (leading to fuzzy nucleosome architectures). We found that the first (+1) and the last (-last) nucleosomes are contiguous to regions signaled by transcription factor binding sites and unusual DNA physical properties that hinder nucleosome wrapping. Based on these analyses, we developed a method that combines Machine Learning and signal transmission theory able to predict the basal locations of the nucleosomes with an accuracy similar to that of experimental MNase-seq based methods.
RNA helicase D1PAS1 resolves R-loops and forms a complex for mouse pachytene piRNA biogenesis required for male fertility
Authors: Choi Heejin , Zhou Lecong , Zhao Yangu , Dean Jurrien
Published: August 2024

During meiosis, RNA polymerase II transcribes pachytene piRNA precursors with unusually long and unspliced transcripts from discrete autosomal loci in the mouse genome. Despite the importance of piRNA for male fertility and a well-defined maturation process, the transcriptional machinery remains poorly understood. Here, we document that D1PAS1, an ATP-dependent RNA helicase, is critical for pachytene piRNA expression from multiple genomic loci and subsequent translocation into the cytoplasm to ensure mature piRNA biogenesis. Depletion of D1PAS1 in gene-edited mice results in the accumulation of R-loops in pachytene spermatocytes, leading to DNA-damage-induced apoptosis, disruption of piRNA biogenesis, spermatogenic arrest, and male infertility. Transcriptome, genome-wide R-loop profiling, and proteomic analyses document that D1PAS1 regulates pachytene piRNA transcript elongation and termination. D1PAS1 subsequently forms a complex with nuclear export components to ensure pachytene piRNA precursor translocation from the nucleus to the cytoplasm for processing into small non-coding RNAs. Thus, our study defines D1PAS1 as a specific transcription activator that promotes R-loop unwinding and is a critical factor in pachytene piRNA biogenesis.
Geminivirus C4/AC4 proteins hijack cellular COAT PROTEIN COMPLEX I for chloroplast targeting and viral infections
Authors: Zhao Wenhao , Ji Yinghua , Zhou Yijun , Wang Xiaofeng
Published: August 2024

Geminiviruses infect numerous crops and cause extensive agricultural losses worldwide. During viral infection, geminiviral C4/AC4 proteins relocate from the plasma membrane to chloroplasts, where they inhibit the production of host defense signaling molecules. However, mechanisms whereby C4/AC4 proteins are transported to chloroplasts are unknown. We report here that tomato (Solanum lycopersicum) COAT PROTEIN COMPLEX I (COPI) components play a critical role in redistributing Tomato yellow leaf curl virus C4 protein to chloroplasts via an interaction between the C4 and β subunit of COPI. Coexpression of both proteins promotes the enrichment of C4 in chloroplasts that is blocked by a COPI inhibitor. Overexpressing or downregulating gene expression of COPI components promotes or inhibits the viral infection, respectively, suggesting a proviral role of COPI components. COPI components play similar roles in C4/AC4 transport and infections of two other geminiviruses: Beet curly top virus and East African cassava mosaic virus. Our results reveal an unconventional role of COPI components in protein trafficking to chloroplasts during geminivirus infection and suggest a broad-spectrum antiviral strategy in controlling geminivirus infections in plants.
A Diagnostic Guide for Berkeleyomyces rouxiae Causing Black Root Rot of Cotton
Authors: Le Duy P. , Nguyen Chi P. T. , Manjarrez Maria , Giblot-Ducray Daniele
Published: August 2024

Black root rot (BRR) is a major seedling disease of cotton in Australia. The disease is caused by Berkeleyomyces rouxiae (formerly known as Thielaviopsis basicola), which is morphologically identical to B. basicola. In this diagnostic guide, we share current work and knowledge regarding B. rouxiae in cotton in Australia. This guide includes comprehensive signs and symptoms to allow correct identification of the disease in the field. Methods and tricks to isolate and purify the pathogen from soil and diseased cotton are also discussed. Additionally, available molecular approaches for accurate identification of B. rouxiae are summarized. Last but not least, methods to preserve and assess pathogenicity of B. rouxiae on cotton are presented.
Risk Factors Related to the Development of Full-thickness Pressure Injuries in Hospitalized Pediatric Patients
Authors: Nie Ann Marie , Hawkins-Walsh Elizabeth , Delmore Barbara
Published: August 2024

BACKGROUND

Current pediatric pressure injury (PI) prevention measures are based on risk factors related to PI development in adults. Children offer a unique concern for PI development because their bodies are still developing, and their skin responds differently to external pressure.

OBJECTIVE

To explore risk factors for the development of full-thickness PIs in children aged 21 weeks’ gestation to 21 years.

METHODS

This retrospective, observational, correlational study included 799 hospitalized children who developed a PI. The pediatric and adult PI risk factors used in the study were identified from the International Pressure Ulcer Prevention and Treatment Guideline. A stepwise multivariate logistic regression model was used.

RESULTS

Multivariate analyses revealed that risk factors for predicting a full-thickness PI varied by age. For children aged 38 weeks to 12 months, risk factors included tissue perfusion and oxygenation: generalized edema, conditions of the OR, and nutrition deficits. For children aged 1 to 7 years, fragile skin status was a risk factor. For youth aged 8 to 21 years, the two risk factors were tissue perfusion and oxygenation: decreased oxygenation and extracorporeal membrane oxygenation. Across the total sample, extracorporeal membrane oxygenation, tissue perfusion and oxygenation: decreased oxygenation and malnutrition were risk factors for predicting a full-thickness PI.

CONCLUSIONS

Full-thickness PI risk factors differ among the ages of pediatric patients.
Evaluating Intensive Care Nurses’ Knowledge of Incontinence-Associated Dermatitis: A Multicenter Cross-sectional Study
Authors: Kılıç Meryem , Tuncay Asiye , Çakır Sümeyra Benan
Published: August 2024

OBJECTIVE

To determine the knowledge levels of nurses working in the ICU about incontinence-associated dermatitis (IAD).

METHODS

A descriptive cross-sectional study was conducted in adult ICUs at two private and three public hospitals in a province in Turkey. The study included 296 nurses who agreed to participate in the research. Researchers used the “Nurse Identification Form” and the “IAD Knowledge Test” to collect data on nurses’ IAD knowledge. Data analysis included the use of percentage distribution and the Mann-Whitney U, Kruskal-Wallis, and Spearman correlation tests.

RESULTS

The mean age of the nurses was 26.55 ± 3.89 years (range, 20-47 years), and the duration of working in the ICU was 2.71 ± 2.55 years (range, 1-22 years). Of the nurses, 183 (61.8%) worked in general ICUs. Of those, 69 (23.3%) received IAD training. Nurses achieved a 49.8% correct response rate on the IAD knowledge test. Nurses working in tertiary and general ICUs demonstrated higher IAD knowledge levels (Ps = .003 and .047, respectively). There were no relationships between age, career length, institution, ICU type, and IAD knowledge level.

CONCLUSIONS

Nurses’ knowledge level of IAD was low in intensive care. To remedy this, IAD should be added to intensive care nursing certificate programs as content, and the use of IAD risk assessment and diagnosis scales in ICUs should be expanded.
Proteomic Profiling of Hindlimb Skeletal Muscle Disuse in a Murine Model of Sepsis
Authors: Boeno Franccesco P. , Roesch Luiz Fernando W. , Efron Philip A. , Laitano Orlando
Published: August 2024

CONTEXT:

Sepsis leads to multiple organ dysfunction and negatively impacts patient outcomes. Skeletal muscle disuse is a significant comorbidity in septic patients during their ICU stay due to prolonged immobilization.

HYPOTHESIS:

Combination of sepsis and muscle disuse will promote a unique proteomic signature in skeletal muscle in comparison to disuse and sepsis separately.

METHODS AND MODELS:

Following cecal ligation and puncture (CLP) or Sham surgeries, mice were subjected to hindlimb suspension (HLS) or maintained normal ambulation (NA). Tibialis anterior muscles from 24 C57BL6/J male mice were harvested for proteomic analysis. Proteomic profiles were assessed using nano-liquid chromatography with tandem mass spectrometry, followed by data analysis including Partial Least Squares Discriminant Analysis (PLS-DA), to compare the differential protein expression across groups.

RESULTS:

A total of 2876 differentially expressed proteins were identified, with marked differences between groups. In mice subjected to CLP and HLS combined, there was a distinctive proteomic signature characterized by a significant decrease in the expression of proteins involved in mitochondrial function and muscle metabolism, alongside a marked increase in proteins related to muscle degradation pathways. The PLS-DA demonstrated a clear separation among experimental groups, highlighting the unique profile of the CLP/HLS group. This suggests an important interaction between sepsis-induced inflammation and disuse atrophy mechanisms in sepsis-induced myopathy.

INTERPRETATIONS AND CONCLUSIONS:

Our findings reveal a complex proteomic landscape in skeletal muscle exposed to sepsis and disuse, consistent with an exacerbation of muscle protein degradation under these combined stressors. The identified proteins and their roles in cellular stress responses and muscle pathology provide potential targets for intervention to mitigate muscle dysfunction in septic conditions, highlighting the importance of addressing both sepsis and disuse concurrently in clinical and experimental settings.
Diverse Phenotypic Presentation of the Welander Distal Myopathy Founder Mutation, With Myopathy and Amyotrophic Lateral Sclerosis in the Same Family
Authors: Purcell Nicholas , Manousakis Georgios
Published: August 2024

Welander distal myopathy is a rare myopathy with prominent and early involvement of distal upper extremity muscles, prevalent in individuals of Scandinavian origin, and caused by a founder mutation in the cytotoxic granule-associated RNA-binding protein (T-cell intracellular antigen-1; TIA1), E384K. Different pathogenic variants in the TIA1 gene, distinct from the founder 1, have recently been associated with frontotemporal dementia and amyotrophic lateral sclerosis (ALS), suggesting that TIA1-related disorders belong to the group of multisystem proteinopathies. We describe the first case of a two-generation family with the founder E384K TIA1 mutation demonstrating phenotypic variability; the mother manifested as Welander myopathy, whereas 2 daughters manifested as ALS. No other genetic cause of ALS was found in 1 of the affected daughters. We also discuss the possible mechanisms explaining this pleotropic presentation of the founder mutation.
Obstructive Bilateral Renal Fungal Bezoars in an Extremely Premature Neonate Treated With Antifungals and Urokinase Irrigation: A Case Report and Review of the Literature
Authors: Davis Kimberly , Yap Natalie , Clark Megan , Bhatia Risha , Johnstone Lilian , Taghavi Kiarash , O’Brien Matthew , Ching Natasha , Carr Jeremy
Published: August 2024

Background:

An ex-27-week gestation female infant developed bilateral forearm nodules at 4 weeks of life during treatment for methicillin-sensitive Staphylococcus aureus bacteremia. A pure growth of Candida albicans was isolated on culture of both sterile aspiration of the forearm abscess and urine without evidence of methicillin-sensitive Staphylococcus aureus. The patient went on to develop bilateral obstructive renal fungal bezoars at 11 weeks of life.

Results:

Bilateral nephrostomies were required to alleviate obstruction with the addition of local irrigation with amphotericin B deoxycholate. Two weeks later, urokinase via the nephrostomy tubes was added due to an unchanged appearance on ultrasound (US) and ongoing candiduria. A significant reduction in the size of bezoars was seen on US after 3 days. Sterilization of urine culture was achieved 7 weeks into treatment, and resolution of bezoars on US was seen 9 weeks after treatment began. No adverse events occurred from the use of local urokinase.

Conclusions:

Urokinase irrigation via nephrostomy is an effective and safe adjunctive treatment in refractory obstructive renal candidiasis in neonates.
Mycobacterium fortuitum: A Rare Cause of Surgical Site Infection
Authors: Muruzábal Cecilia , Rico-Nieto Alicia , Baquero-Artigao Fernando , Fernández-Sampedro Marta , Runza Buznego Paula , Sánchez-Márquez José Miguel , Pizones Javier , Quiles María Inmaculada , San Juan Isabel , Grasa Carlos , Calvo Cristina
Published: August 2024

Mycobacterium fortuitum is a rapidly growing nontuberculous mycobacterium mainly associated with skin, soft tissue and surgical site infections. We report an unusual outbreak of 6 cases of surgical site infection following spinal surgery. Patients received combined intravenous antibiotics, including amikacin, followed by an extended period of oral therapy with favorable clinical outcomes. No instrumentation replacement was performed in any case.
Tips From the Iceberg: Effecting Culture Change in Health Care Teams
Authors: Sherrer D. Matthew , Vining Brooke R. , Rich Martha Anne
Published: August 2024

For centuries, fables have been used as teaching aids that bring simple lessons to life through storytelling. The extensive research of John Kotter has been distilled into fable form in the book “Our Iceberg is Melting.” Here, we will describe an instance of applying Kotter’s eight-step model to overcome relational tension between anesthesiologists and nurse anesthetists and a resultant culture of collaboration at 2 of the authors’ academic medical centers.
Substantiating the Use of Tendotonometry for the Assessment of Achilles and Patellar Tendon Stiffness: A Systematic Review
Authors: van Dam Lotte , Fischer Rosanne , Baart Mireille , Zwerver Johannes
Published: August 2024

Objective:

To systematically describe the next relevant aspects of tendotonometry in (1) its validity and reliability, (2) differences between populations, (3) the effect of interventions, and (4) differences between healthy and symptomatic Achilles tendon (AT) and patellar tendon (PT).

Data Sources:

Three online databases (PubMed, Embase, and EBSCOhost) were systematically searched on the 10th of October 2023. All scientific literature concerning the use of tendotonometry in assessing tendon stiffness was collected. Articles were eligible if tendotonometry with a myotonometer digital palpation device was used to assess PT or AT stiffness in adults.

Main results:

Thirty-four studies were included, which were categorized into studies regarding the (1a) reliability and (1b) validity of tendotonometry, (2) differences in stiffness between populations, (3) changes in stiffness due to interventions, (4) stiffness of healthy compared with injured tendons, and (5) other observational studies. The inter-rater and intrarater reliability of tendotonometry appeared to be good in assessing AT and PT stiffness, with only moderate evidence for the AT and inconclusive evidence for the PT. There is high certainty evidence that tendotonometry can detect differences in AT and PT stiffness after training interventions. Inconsistent results were found for the adequacy of tendotonometry to detect differences in AT and PT stiffness between populations.

Conclusions:

This review shows a potential role for tendotonometry in measuring tendon stiffness. However, more research is needed for validating the use of tendotonometry in AT and PT and its exact clinical interpretation.
Creating an inpatient prechemotherapy checklist for nurses
Authors: Akouaou Fatima , Breda Karen , Karl Cherry
Published: August 2024

Inpatient oncology nurses are responsible for providing patient teaching; however, there's a lack of standardized procedures and education materials available to support these professionals.
Nursing management of acute ischemic stroke
Authors: Travers Jennifer , Bazaar Celina
Published: August 2024

An acute ischemic stroke is a life-threatening and life-altering medical emergency. The role of the nurse includes assessment, identification, monitoring, psychological support, and rehabilitation for the patient, family, and caregivers.
Circumstances and Pathological Findings in Civilian Helicopter-Related Fatalities
Authors: Tiemensma Marianne , Prahladh Salona , Byard Roger W.
Published: August 2024

Helicopters are used worldwide in a range of commercial and private industries and are particularly useful in northern Australia due to the sparse population scattered over large distances with remote regions difficult to access by any other means of transport. Nine civilian helicopter-related fatalities were reported to the Northern Territory coroner between January 2004 and December 2023. The victims were all male (age range, 34–74 years; mean, 52 years). All fatal crashes occurred in remote areas, the majority on cattle stations. Pilots were the sole occupants in 5/9 incidents; in 4 incidents, there were injured survivors. All fatal incidents involved Robinson piston engine helicopters (Robinson R44 models in 2 incidents and Robinson R22 models in the remaining 7). Scene investigations, postmortem examinations, and ancillary investigations were frequently hampered by decomposition of the remains, resulting from difficult search operations and delayed location, retrieval, and storage. Head injuries were present in all cases with chest and spinal injuries in more than half. Integrated assessment of injuries with toxicological and aviation investigations facilitated understanding of the crash dynamics.
Focused Ultrasound
Authors: Moonen Chrit T.W. , Kilroy Joseph P. , Klibanov Alexander L.
Published: August 2024

Invasive open surgery used to be compulsory to access tumor mass to perform excision or resection. Development of minimally invasive laparoscopic procedures followed, as well as catheter-based approaches, such as stenting, endovascular surgery, chemoembolization, brachytherapy, which minimize side effects and reduce the risks to patients. Completely noninvasive procedures bring further benefits in terms of reducing risk, procedure time, recovery time, potential of infection, or other side effects. Focusing ultrasound waves from the outside of the body specifically at the disease site has proven to be a safe noninvasive approach to localized ablative hyperthermia, mechanical ablation, and targeted drug delivery. Focused ultrasound as a medical intervention was proposed decades ago, but it only became feasible to plan, guide, monitor, and control the treatment procedures with advanced radiological imaging capabilities. The purpose of this review is to describe the imaging capabilities and approaches to perform these tasks, with the emphasis on magnetic resonance imaging and ultrasound. Some procedures already are in clinical practice, with more at the clinical trial stage. Imaging is fully integrated in the workflow and includes the following: (1) planning, with definition of the target regions and adjacent organs at risk; (2) real-time treatment monitoring via thermometry imaging, cavitation feedback, and motion control, to assure targeting and safety to adjacent normal tissues; and (3) evaluation of treatment efficacy, via assessment of ablation and physiological parameters, such as blood supply. This review also focuses on sonosensitive microparticles and nanoparticles, such as microbubbles injected in the bloodstream. They enable ultrasound energy deposition down to the microvascular level, induce vascular inflammation and shutdown, accelerate clot dissolution, and perform targeted drug delivery interventions, including focal gene delivery. Especially exciting is the ability to perform noninvasive drug delivery via opening of the blood-brain barrier at the desired areas within the brain. Overall, focused ultrasound under image guidance is rapidly developing, to become a choice noninvasive interventional radiology tool to treat disease and cure patients.
SQUIRE-SIM (Standards for Quality Improvement Reporting Excellence for SIMulation)
Authors: Stone Kimberly P. , Rutman Lori , Calhoun Aaron W. , Reid Jennifer , Maa Tensing , Bajaj Komal , Auerbach Marc A. , Cheng Adam , Davies Louise , Deutsch Ellen , Harwayne-Gidansky Ilana , Kessler David O. , Ogrinc Greg , Patterson Mary , Thomas Anita , Doughty Cara ,   And for the International Network in Simulation-Based Innovation, Research and Education (INSPIRE) SQUIRE-SIM Reporting Guidelines Investigators
Published: August 2024

Introduction

With increased incorporation of simulation-based methodologies into quality improvement activities, standards for reporting on simulation-specific elements in healthcare improvement research are needed.

Methods

We followed established consensus process methodology to iteratively create simulation-based extensions for SQUIRE 2.0 reporting guidelines. Initial steps involved forming a steering committee, defining the scope, and conducting premeeting activities with an expert panel of simulation and quality improvement researchers. Recommendations from the expert panel were brought to a consensus meeting where existing guidelines were reviewed and recommendations made. Steering Committee members reviewed all recommendations, reconciled differences, and made final recommendations, which were piloted by experienced simulation and quality improvement researchers.

Results

Fifteen Steering Committee members, 59 experts in simulation and quality improvement research, and 86 consensus meeting attendees reviewed SQUIRE 2.0 reporting guidelines and ultimately recommended simulation-based reporting guidelines for 22 of the 41 (54%) SQUIRE 2.0 guidelines. Those items for which simulation-based extensions were identified were: Notes to Authors, 1 (Title), 2a (Abstract), 2b (Abstract), 4 (Introduction: Available knowledge), 5 (Introduction: Rationale), 7 and 8a & b (Methods: Context and intervention), 9a (Methods – Study of the intervention), 9b (Methods – Study of the intervention), 10a (Methods – Measures), 10b (Methods-Measures), 10c (Methods-Measures), 11b (Methods- Analysis), 12 (Methods – Ethical considerations), 13a (Results), 13e (Results), 14b (Discussion – Summary), 15a-e (Discussion – Interpretation), 16a (Discussion – Limitations), 16b (Discussion – Limitations), 17c (Discussion – Conclusions), and 17d (Discussion – Conclusions).

Conclusions

We created simulation-based extensions to SQUIRE 2.0 reporting guidelines to improve the quality and standardization of reporting on simulation-specific elements of healthcare improvement research.
The effect of pH on the structure of Bluetongue virus VP5
Authors: Zhang Hanwen , El Omari Kamel , Sutton Geoff , Stuart David I.
Published: August 2024

The unenveloped Bluetongue virus capsid comprises several structural layers, the inner two comprising a core, which assembles before addition of the outer proteins, VP2 and VP5. Two symmetric trimers of VP5 fit like pegs into two distinct pits on the core and undergo pH conformational changes in the context of the virus, associated with cell entry. Here we show that in isolation VP5 alone undergoes essentially the same changes with pH and confirm a helical transition, indicating that VP5 is a motor during cell entry. In the absence of VP5 the two pits on the core differ from each other, presumably due to the asymmetric underlying structure of VP3, the innermost capsid protein. On insertion of VP5 these pits become closely similar and remain similar at low pH whilst VP5 is present. This natural asymmetry presumably destabilises the attachment of VP5, facilitating ejection upon low pH, membrane penetration and cell entry.
LncRNA PVT1 in brain injury induced by deep hypothermia and low flow
Authors: Yang Yuzhong , Ma Siyu , Zang Xiaodong , Mo Xuming
Published: August 2024

Aims

To analyze the role of lncRNA PVT1 in cerebral ischemia-reperfusion (I/R) injury induced by deep hypothermia low flow (DHLF).

Methods and results

A total of 72 lncRNAs were differentially expressed in the brain tissue of DHLF mice. PVT1 expression was significantly downregulated in DHLF mouse brain tissue, preoperative and postoperative blood samples from children undergoing DHLF extracorporeal circulation, and hOGD-treated cells. In the mouse model, the DHLF group with PVT1 overexpression had heavier brain tissue damage than the control group; apoptosis rate, reactive oxygen species level and caspase-3 enzyme activity were significantly higher in the lenti-PVT1 group than in the lenti-control group. Compared those in the lenti-control group, the total distance traveled, distance of action in the center, number of entering the center, average speed of walking reduced, and the distance of walking in the periphery and and peripheral walking distance increased in the lenti-PVT1 group. The dual luciferase reporter gene assay verified the possible binding sites between PVT1, miR-148a-3p and MKL1. In the animal model, cellular model, and blood samples of children experiencing DHLF, miR-148a-3p expression increased and MKL1 expression decreased. In experimental studies in vivo and in vitro, PVT1 and MKL1 expression increased, and miR-148a-3p expression decreased. Meanwhile MKL1 inhibitor CCG1423 reversed the apoptosis in neuronal cells.

Conclusion

PVT1 may adsorb miR-148a-3p to regulate the expression of MKL1, a downstream gene of miR-148a-3p, a mechanism promoting the apoptosis of neuronal cells in DHLF mice.
Privacy Protection of Sexually Transmitted Infections Information from Chinese Electronic Medical Records
Authors: Gong Mengchun , Yu Yue , Ouyang Zihao , Shi Wenzhao , Liu Chao , Wang Qilin , Nan Jiale , Cai Endi , Ding Fen , Nie Sheng
Published: August 2024

Objectives

To formulate an efficacious approach for safeguarding the privacy information of electronic medical records.

Design

Chinese patient electronic medical record text information.

Setting

The Chinese Renal Disease Data System database.

Participants

3,233,174 patients between 1 Jan. 2010 and 31 Dec. 2023.

Main outcome measures

Annotated patient privacy fields and the effectiveness of privacy protection

Results

We have developed an automated tool named EPSTII, designed to protect the privacy of patients’ sexually transmitted infection information within medical records. Through the refinement of keywords and the integration of expert knowledge, EPSTII currently achieves a 100% accuracy and recall rate. Our privacy protection measures have reached a 99.5% success rate, ensuring the utmost protection of STI patients’ privacy. As the first large-scale investigation into privacy leakage and STI identification in Chinese electronic medical records, our research paves the way for the future development of patient privacy protection laws in China and the advancement of more sophisticated tools.

Conclusions

The EPSTII method demonstrates a feasible and effective approach to protect privacy in electronic medical records from 19 hospitals, offering comprehensive insights for infectious disease research using Chinese electronic medical records, with protocols tailored for accurate STI data extraction and enhanced protection compared to traditional methods.
Assessing the effect of social contact structure on the impact of pneumococcal conjugate vaccines
Authors: Wong Anabelle , Kramer Sarah C. , Weinberger Daniel M. , de Cellès Matthieu Domenech
Published: August 2024

Although pneumococcal conjugate vaccines (PCVs) have greatly reduced diseases caused by vaccine-targeted serotypes (VT) ofStreptococcus pneumoniae, vaccine impact may be eroded by the increase in rates of disease caused by non-vaccine serotypes (NVT). Here, we investigated the effect of social contact patterns on the dynamics of vaccine impact in carriage.

We developed a neutral, age-structured, Susceptible–Colonized model incorporating VT-NVT co-colonization and verified it against real-world carriage data in children. Using contact matrices from 34 countries, we assessed the impact of contact patterns on the time required to eliminate VT (i.e., 95% reduction in VT proportion in carriage). Finally, we quantified the contribution of various parameters—such as vaccine efficacy, coverage, immunity waning, and population susceptibility—to the dynamics of VT elimination.

Our model recapitulated the observed decline of VT carriage and showed that varying the contact structure alone led to different time-to-elimination. We found that higher total contact rate and assortativity in children under 5 accelerated VT elimination. Additionally, higher vaccine efficacy and coverage, and slower immunity waning led to shorter time-to-elimination.

These findings illuminate the mechanisms controlling the dynamics of vaccine impact and may help predict the impact of PCVs in communities with different contact patterns.
Primary care transformation in Scotland: a comparison two cross-sectional national surveys of general practitioners’ views in 2018 and 2023
Authors: Donaghy E , Sweeney KD , Lauren Ng , Haines Holly , Thompson Alexandra , Henderson D , Wang HHX , Thompson A , Guthrie B , Mercer SW
Published: August 2024

Objectives

The new general practitioner (GP) contract for Scotland, introduced in 2018, established GP Clusters and expanded multidisciplinary team (MDT) working. This paper compares the views of GPs in Scotland regarding the new contract, their working lives, and career intentions in 2018 and 2023.

Methods

Cross-sectional postal survey of all qualified GPs in Scotland in late 2023 exploring views on Cluster working, MDT-expansion, their working lives, and career intentions, compared with a similar survey from 2018.

Results

Job pressure was significantly higher in 2023 than 2018, but overall job satisfaction and negative job attributes were unchanged, while positive job attributes improved. More GPs were planning to reduce their hours and leave direct patient care in 2023 than 2018.

Quality leads views on Cluster working were unchanged, with 70-80% reporting insufficient support in both surveys. Cluster knowledge and engagement was unchanged but all GPs showed small but significant increases in understanding of quality improvement. Most felt MDT expansion was insufficient to reduce workload and fewer GPs reported giving longer consultations for complex patients in 2023 than 2018. Significantly more practices were trying to recruit GPs in 2023, and GPs reported worsening NHS services, higher workload, and lower practice sustainability. Only 1 in 20 GPs in the 2023 survey thought that the new contract had improved the care of patients with multimorbidity.

Conclusions

GPs report few improvements in working life five years after the new contract was introduced, and are responding by planning to reduce their hours or leave direct patient care.
Local genetic covariance analysis with lipid traits identifies novel loci for early-onset Alzheimer’s Disease
Authors: Ray Nicholas R. , Bradley Joseph , Yilmaz Elanur , Kizil Caghan , Kurup Jiji T. , Martin Eden R. , Klein Hans-Ulrich , Kunkle Brian W. , Bennett David A. , de Jager Philip L. ,   Alzheimer’s Disease Genetics Consortium, Beecham Gary W. , Cruchaga Carlos , Reitz Christiane
Published: August 2024

Background

The genetic component of early-onset Alzheimer’s disease (EOAD), accounting for ∼10% of all Alzheimer’s disease (AD) cases, is largely unexplained. Recent studies suggest that EOAD may be enriched for variants acting in the lipid pathway.

Objective

To examine the shared genetic heritability between EOAD and the lipid pathway by genome-wide multi-trait genetic covariance analyses.

Methods

Summary statistics were obtained from the GWAS meta-analyses of EOAD by the Alzheimer’s Disease Genetics Consortium (n=19,668) and five blood lipid traits by the Global Lipids Genetics Consortium (n=1,320,016), and genetic covariance analyses were performed via SUPERGNOVA. Genes in linkage disequilibrium (LD) with top EOAD hits in identified regions of covariance with lipid traits were scored and ranked for causality by combining evidence from gene-based analysis, AD-risk scores incorporating transcriptomic and proteomic evidence, eQTL data, eQTL colocalization analyses, DNA methylation data, and single-cell RNA sequencing analyses.

Results

Local genetic covariance analyses identified 3 regions of covariance between EOAD and at least one lipid trait. Gene prioritization nominated 3 likely causative genes at these loci:ANKDD1B,CUZD1, andMS4A64.

Conclusion

The current study identified genetic covariance between EOAD and lipids, providing further evidence of shared genetic architecture and mechanistic pathways between the two traits.
Paramagnetic Rim Lesions are Highly Specific for Multiple Sclerosis in Real-World Data
Authors: Hemond Christopher C. , Dundamadappa Sathish K. , Deshpande Mugdha , Baek Jonggyu , Brown Robert H. , Ionete Carolina , Reich Daniel S.
Published: August 2024

Background

Paramagnetic rim lesions (PRL) are an emerging biomarker for multiple sclerosis (MS). In addition to associating with greater disease severity, PRL may be diagnostically supportive.

Objective

Our aim was to determine PRL specificity and sensitivity for discriminating MS from its diagnostic mimics using real-world clinical diagnostic and imaging data.

Methods

This is a retrospective, cross-sectional analysis of a longitudinal cohort of patients with prospectively collected observational data. Patients were included if they underwent neuroimmunological evaluation in our academic MS center, and had an available MRI scan from the same clinical 3T magnet that included a T2*-weighted sequence with susceptibility postprocessing (SWAN protocol, GE). SWAN-derived filtered phase maps and corresponding T2-FLAIR images were manually reviewed to determine PRL. PRL were categorized as “definite,” “probable,” or “possible” based on modified, recent consensus criteria. We hypothesized that PRL would convey a high specificity to discriminate MS from its MRI mimics.

Results

580 patients were evaluated in total: 473 with MS, 57 with non-inflammatory neurological disease (NIND), and 50 with other inflammatory neurological disease (OIND). Identification of “definite” or “probable” PRL provided a specificity of 98% to discriminate MS from NIND and OIND; sensitivity was 36%. Interrater agreement was almost perfect for definite/probable identification at a subject level.

Conclusions

PRL convey high specificity for MS and can aid in the diagnostic evaluation. Modest sensitivity limits their use as single diagnostic indicators. Including lesions with lower confidence (“possible” PRL) rapidly erodes specificity and should be interpreted with caution given the potential harms associated with misdiagnosis.
Cost-effectiveness of leveraging existing HIV primary health systems and community health workers for hypertension screening and treatment in Africa: an individual-based modelling study
Authors: Hickey Matthew D , Ayieko James , Kabami Jane , Owaraganise Asiphas , Kakande Elijah , Ogachi Sabina , Aoko Colette I , Mugoma Erick Wafula , Sang Norton , Sunday Helen , Revill Paul , Bansi-Matharu Loveleen , Shade Starley B , Chamie Gabriel , Balzer Laura B , Petersen Maya , Havlir Diane V , Kamya Moses R , Phillips Andrew N
Published: August 2024

Background Cardiovascular disease (CVD) morbidity and mortality is increasing in Africa, largely due to undiagnosed and untreated hypertension. Approaches that leverage existing primary health systems could improve hypertension treatment and reduce CVD, but cost-effectiveness is unknown. We evaluated the cost-effectiveness of population-level hypertension screening and implementation of chronic care clinics across eastern, southern, central, and western Africa. Methods We conducted a modelling study to simulate hypertension and CVD across 3000 scenarios representing a range of settings across eastern, southern, central, and western Africa. We evaluated two policies compared to current hypertension treatment: 1) expansion of HIV primary care clinics into chronic care clinics that provide hypertension treatment for all persons regardless of HIV status (chronic care clinic or CCC policy), and 2) CCC plus population-level hypertension screening of adults ≥40 years by community health workers (CHW policy). For our primary analysis, we used a cost-effectiveness threshold of US $500 per disability-adjusted life-year (DALY) averted, a 3% annual discount rate, and a 50-year time horizon. A strategy was considered cost-effective if it led to the lowest net DALYs, which is a measure of DALY burden that takes account of the DALY implications of the cost for a given cost-effectiveness threshold. Findings Among adults 45-64 years, CCC implementation would improve population-level hypertension control (the proportion of people with hypertension whose blood pressure is controlled) from mean 4% (90% range 1-7%) to 14% (6-26%); additional CHW screening would improve control to 44% (35-54%). Among all adults, CCC implementation would reduce ischemic heart disease (IHD) incidence by 10% (3-17%), strokes by 13% (5-23%), and CVD mortality by 9% (3-15%). CCC plus CHW screening would reduce IHD by 28% (19-36%), strokes by 36% (25-47%), and CVD mortality by 25% (17-34%). CHW screening was cost-effective in 62% of scenarios, CCC in 31%, and neither policy was cost-effective in 7% of scenarios. Pooling across setting-scenarios, incremental cost-effectiveness ratios were $69/DALY averted for CCC and $389/DALY averted adding CHW screening to CCC. Interpretation Leveraging existing healthcare infrastructure to implement population-level hypertension screening by CHWs and hypertension treatment through integrated chronic care clinics is expected to reduce CVD morbidity and mortality and is likely to be cost-effective in most settings across Africa.
Age at Menarche and Coronary Artery Disease Risk: Divergent Associations with Different Sources of Variation
Authors: Sonawalla Ambreen , Chasman Daniel I. , Chan Yee-Ming
Published: August 2024

Background

In women, both earlier and later age at menarche (AAM) are associated with increased risk of coronary artery disease (CAD). This study sought to determine if the relationship of AAM with CAD and CAD risk factors differs for different underlying sources of variation in AAM – specifically, variation attributable to common genetic variants as represented by a polygenic score (PGS) vs. variation in AAM adjusted for the PGS.

Methods

Primary analyses were conducted on data from 201,037 women in the UK Biobank and validation studies on data from 23,268 women in the Women’s Genome Health Study (WGHS). For each individual, a PGS for AAM was calculated, then two variables were estimated from linear regression models: the genetically predicted AAM (the estimated AAM for each woman solely due to the effects of common genetic variants) and the PGS-adjusted AAM (estimated AAM for each woman solely due to factors other than the PGS). Logistic regression and linear splines were then used to study the relationships of these variables with CAD and CAD risk factors.

Results

Genetically predicted AAM demonstrated a linear relationship with CAD and linear or roughly linear relationships with CAD risk factors. In contrast, PGS-adjusted AAM demonstrated a U-shaped relationship with CAD and with hemoglobin A1c, triglycerides, HDL-C, and waist-hip ratio. Validation studies using WGHS data produced similar results.

Conclusions

These results suggest that later AAM itself does not cause increased risk of CAD; rather, upstream sources of variation other than common genetic variants can cause both later AAM and increased risk of CAD. Dysglycemia, dyslipidemia, and central adiposity are candidate mediators of the association of later AAM with increased risk of CAD.