bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of oxidative stress in neurodegenerative disorders: a review of reactive oxygen species and prevention by antioxidants
Authors: Houldsworth Annwyne
Published: January 2024

Neurological disorders include a variety of conditions, including Alzheimer’s disease, motor neuron disease and Parkinson’s disease, affecting longevity and quality of life, and their pathogenesis is associated with oxidative stress. Several of the chronic neurodegenerative pathologies of the CNS share some common features, such as oxidative stress, inflammation, synapse dysfunctions, protein misfolding and defective autophagia. Neuroinflammation can involve the activation of mast cells, contributing to oxidative stress, in addition to other sources of reactive oxygen species. Antioxidants can powerfully neutralize reactive oxygen species and free radicals, decreasing oxidative damage. Antioxidant genes, like the manganese superoxide dismutase enzyme, can undergo epigenetic changes that reduce their expression, thus increasing oxidative stress in tissue. Alternatively, DNA can be altered by free radical damage. The epigenetic landscape of these genes can change antioxidant function and may result in neurodegenerative disease. This imbalance of free radical production and antioxidant function increases the reactive oxygen species that cause cell damage in neurons and is often observed as an age-related event. Increased antioxidant expression in mice is protective against reactive oxygen species in neurons as is the exogenous supplementation of antioxidants. Manganese superoxide dismutase requires manganese for its enzymic function. Antioxidant therapy is considered for age-related neurodegenerative diseases, and a new mimetic of a manganese superoxide dismutase, avasopasem manganese, is described and suggested as a putative treatment to reduce the oxidative stress that causes neurodegenerative disease. The aim of this narrative review is to explore the evidence that oxidative stress causes neurodegenerative damage and the role of antioxidant genes in inhibiting reactive oxygen species damage. Can the neuronal environment of oxidative stress, causing neuroinflammation and neurodegeneration, be reduced or reversed?
Design of a Level-3 electric vehicle charging station using a 1-MW solar system via the distributed maximum power point tracking technique
Authors: Balal Afshin , Giesselmann Michael
Published: January 2024

Solar power is mostly influenced by solar irradiation, weather conditions, solar array mismatches and partial shading conditions. Therefore, before installing solar arrays, it is necessary to simulate and determine the possible power generated. Maximum power point tracking is needed in order to make sure that, at any time, the maximum power will be extracted from the photovoltaic system. However, maximum power point tracking is not a suitable solution for mismatches and partial shading conditions. To overcome the drawbacks of maximum power point tracking due to mismatches and shadows, distributed maximum power point tracking is utilized in this paper. The solar farm can be distributed in different ways, including one DC–DC converter per group of modules or per module. In this paper, distributed maximum power point tracking per module is implemented, which has the highest efficiency. This technology is applied to electric vehicles (EVs) that can be charged with a Level 3 charging station in <1 hour. However, the problem is that charging an EV in <1 hour puts a lot of stress on the power grid, and there is not always enough peak power reserve in the existing power grid to charge EVs at that rate. Therefore, a Level 3 (fast DC) EV charging station using a solar farm by implementing distributed maximum power point tracking is utilized to address this issue. Finally, the simulation result is reported using MATLAB®, LTSPICE and the System Advisor Model. Simulation results show that the proposed 1-MW solar system will provide 5 MWh of power each day, which is enough to fully charge ~120 EVs each day. Additionally, the use of the proposed photovoltaic system benefits the environment by removing a huge amount of greenhouse gases and hazardous pollutants. For example, instead of supplying EVs with power from coal-fired power plants, 1989 pounds of CO2 will be eliminated from the air per hour.
Pre-operative psoas muscle index, a surrogate for sarcopenia; as a predictor of post-esophagectomy complications
Authors: Yunrong Tan , Jin Wong Wei , Mahendran Hans Alexander , Koon Yoong Boon , Jahit Shukri , Kamaruddin Muhammad Arif , Anuar Nor'Aini , Daud Noor Aida Mat
Published: January 2024

Background

Esophagectomy is the standard of care for curative esophageal cancer. However, it is associated with significant morbidity and mortality. Esophageal cancer is known to negatively affect the nutritional status of patients and many manifest cancer sarcopenia. At present, measures of sarcopenia involve complex and often subjective measurements. We assess whether the Psoas Muscle Index (PMI); an inexpensive, simple, validated method used to diagnose sarcopenia, can be used to predict adverse outcomes in patients after curative esophagectomy.

Methods

Multi-centre, retrospective cohort between 2010-2020, involving all consecutive patients undergoing curative esophagectomy for esophageal cancer in University Malaya Medical Centre, Sungai Buloh Hospital, and Sultanah Aminah Hospital. The cut-off value differentiating low and normal PMI is defined as 443mm2/m2 in males and 326326 mm2/m2 in females. Complications were recorded using the Clavien-Dindo Scale.

Results

There was no statistical correlation between PMI and major post-esophagectomy complications (p-value: 0.495). However, complication profile was different, and patients with low PMIs had higher 30-day mortality (21.7%) when compared with patients with normal PMI (8.1%) (p-value: 0.048).

Conclusions

Although PMI did not significantly predict post-esophagectomy complications, low PMI correlates with higher 30-day mortality, reflecting a lower tolerance for complications among these patients. PMI is a useful, inexpensive tool to identify sarcopenia and aids the patient selection process. This alerts healthcare professionals to institute intensive physiotherapy and nutritional optimization prior to esophagectomy.
Understanding for whom, under what conditions, and how an integrated approach to atrial fibrillation service delivery works: a realist review
Authors: Pearsons Alice , Hanson Coral L , Hendriks Jeroen M , Neubeck Lis
Published: January 2024

Aims

To understand for whom, under what conditions, and how an integrated approach to atrial fibrillation (AF) service delivery works (or does not work).

Methods and results

A realist review of integrated approaches to AF service delivery for adult populations aged ≥18 years. An expert panel developed an initial programme theory, searched and screened literature from four databases until October 2022, extracted and synthesized data using realist techniques to create context–mechanism–outcome configurations for integrated approaches to AF service, and developed an integrated approach refined programme theory. A total of 5433 documents were screened and 39 included. The refined programme theory included five context–mechanism–outcome configurations for how clinical and system-wide outcomes are affected by the way integrated approaches to AF service delivery are designed and delivered. This review identifies core mechanisms underpinning the already known fundamental components of integrated care. This includes having a central coordinator responsible for service organization to provide continuity of care across primary and secondary care ensuring services are patient centred. Additionally, a fifth pillar, lifestyle and risk factor reduction, should be recognized within an AF care pathway.

Conclusion

It is evident from our provisional theory that numerous factors need to interlink and interact over time to generate a successfully integrated model of care in AF. Stakeholders should embrace this complexity and acknowledge that the learnings from this review are integral to shaping future service delivery in the face of an aging population and increased prevalence of AF.
The long-term effect of an m-health tool on self-care in patients with heart failure: a pre–post interventional study with a mixed-method analysis
Authors: Liljeroos Maria , Arkkukangas Marina , Strömberg Anna
Published: January 2024

Aims

The aims of this study were (i) to evaluate the effects of using an m-health tool on self-care behaviour at 3 and 12 months and (ii) to explore the experiences and perceptions of heart failure (HF) patients about the m-health tool.

Methods and results

In this pre–post interventional study with a mixed-method analysis, 71 patients diagnosed with HF [49% female, mean age 76.7 years, New York Heart Association (NYHA) II 31%, NYHA III 69%] were enrolled and had the m-health tool installed in their home for 1 year. The tool consisted of a pre-programmed tablet including a weighing scale and interactive education about HF self-care. At baseline, and at 3 and 12 months, self-care was assessed using the European Heart Failure Self-care Behaviour (EHFScB-9) Scale, an eight-item self-administered questionnaire assessing the experiences of the m-health tool. The mean EHFScB-9 at baseline was 63.8 ± 2.8 and it improved to 67.6 ± 7.6 after 3 months (P < 0.05). After 1 year, the score had decreased to 63.2 ± 7.1 (P = 0.68). Most patients rated the tool as ‘good’, both at 3 months (92%) and after 12 months (93%). Some found the system to be unnecessary to some degree, and this number increased between 3 and 12 months (P < 0.001). Most patients felt that m-health increased their feelings of security, and 85% responded that the system increased their family members’ sense of security.

Conclusion

The m-health tool significantly improved patients’ self-care behaviour after 3 months, but this effect did not persist after 1 year. For achieving long-term effects and outcomes, additional and regularly updated self-care support may be needed.

Registration

ClinicalTrials.gov: NCT04955600
Analysis of prescription compliance and influencing factors in cardiac rehabilitation after surgery in children with congenital heart disease based on generalized trust theory
Authors: Shen Xiao-Yi , Chen Lin , Yuan Li , Zhu Ya-qi , Cai Xiao-Man , Guan Yong-Mei , Luo Wen-Yi
Published: January 2024

Aims

To understand the compliance, influencing factors, and action path of family cardiac rehabilitation exercise prescriptions for children after congenital heart disease surgery.

Methods and results

A random sampling method was used to select 200 paediatric patients and their parents from a paediatric hospital in Shanghai. Among them, 57 cases (28.5%) of children’s families followed the cardiac rehabilitation exercise prescription. Path analysis showed that peak oxygen uptake exerted a negative impact on the compliance of family cardiac-rehabilitation prescriptions for patients after congenital heart disease surgery through doctor–patient trust, with a standardized path coefficient of −0.246 (P = 0.001). Disease-related knowledge exerted a positive effect on the compliance of family cardiac-rehabilitation prescriptions for children after congenital heart surgery through doctor–patient trust, with a standardized path coefficient of 0.353 (P < 0.001). The dimension of friend support in social support had a direct positive effect on the compliance of family cardiac-rehabilitation prescriptions for children after cardiac surgery, with a standardized path coefficient of 0.641 (P = 0.006).

Conclusion

The compliance of cardiac rehabilitation exercise prescription in children with congenital heart disease is not good and is affected by many factors, and there is a complex path relationship between various factors; the kilogram oxygen consumption of the child, the disease-related knowledge of the caregiver, and social support all play important roles in the compliance of the child’s family’s health prescription.

Registration

ChiCTR2200062022
Respiratory control minimizes diaphragmatic contraction and dry cough during pulsed-field ablation of atrial fibrillation
Authors: Jiang Ruhong , Liu Qiang , Chen Laite , Chen Shiquan , Wang Yunhe , Cheng Hui , Sheng Xia , Sun Yaxun , Yu Lu , Zhang Pei , Lin Jianwei , Zhang Zuwen , Ding Xueyan , Shehata Michael , Fu Guosheng , Jiang Chenyang
Published: January 2024

Aims

Pulsed-field ablation (PFA) is a promising new ablation modality to treat atrial fibrillation. However, PFA can cause varying degrees of diaphragmatic contraction and dry cough, especially under conscious sedation. This prospective study presents a method to minimize the impact of PFA on diaphragmatic contraction and dry cough during the procedure.

Methods and results

Twenty-eight patients underwent PFA for pulmonary vein (PV) and superior vena cava isolation under conscious sedation. Each patient received two groups of ablations in each vein: the control group allowed PFA application during any phase of respiratory cycle, while the test group used respiratory control, delivering PFA energy only at the end of expiration. A rating score system was developed to assess diaphragmatic contraction and dry cough. A total of 1401 control ablations and 4317 test ablations were performed. The test group had significantly lower scores for diaphragmatic contraction (P < 0.01) and dry cough (P < 0.001) in all PVs compared to the control group. The average relative reductions in scores for all PVs were 33–47% for diaphragmatic contraction and 67–83% for dry cough. The percentage of ablations with scores ≧2 for diaphragmatic contraction decreased significantly from 18.5–28.0% in the control group to 0.4–2.6% in the test group (P < 0.001). For dry cough, the percentage decreased from 11.9–43.7% in the control group to 0.7–2.1% in the test group.

Conclusion

Pulsed-field ablation application at the end of expiration can reduce the severity of diaphragmatic contraction and eliminate moderate and severe dry cough during PV isolation performed under conscious sedation.
Clinical Manifestations of an Outbreak of Monkeypox Virus in Captive Chimpanzees in Cameroon, 2016
Authors: Brien Stephanie C , LeBreton Matthew , Doty Jeffrey B , Mauldin Matthew R , Morgan Clint N , Pieracci Emily G , Ritter Jana M , Matheny Audrey , Tafon Bibila G , Tamoufe Ubald , Missoup Alain D , Nwobegahay Julius , Takuo Jean Michel , Nkom Felix , Mouiche Moctar M M , Feussom Jean Marc K , Wilkins Kimberly , Wade Abel , McCollum Andrea M
Published: January 2024

Monkeypox virus (MPXV) is a reemerging virus of global concern. An outbreak of clade I MPXV affected 20 captive chimpanzees in Cameroon in 2016. We describe the epidemiology, virology, phylogenetics, and clinical progression of this outbreak. Clinical signs included exanthema, facial swelling, perilaryngeal swelling, and eschar. Mpox can be lethal in captive chimpanzees, with death likely resulting from respiratory complications. We advise avoiding anesthesia in animals with respiratory signs to reduce the likelihood of death. This outbreak presented a risk to animal care staff. There is a need for increased awareness and a One Health approach to preparation for outbreaks in wildlife rescue centers in primate range states where MPXV occurs. Control measures should include quarantining affected animals, limiting human contacts, surveillance of humans and animals, use of personal protective equipment, and regular decontamination of enclosures.
Antibiotic susceptibility patterns of pathogens isolated from hospitalized patients with advanced HIV disease (AHD) in Bihar, India
Authors: Kumar Vikash , Murali Shreyas , Goldberg Jacob , Alonso Beatriz , Moretó-Planas Laura , Reid Anthony , Harshana Amit , Burza Sakib , Mahajan Raman
Published: January 2024

Objectives

To describe the prevalence of common bacterial pathogens and antibiotic susceptibility patterns amongst advanced HIV disease (AHD) patients admitted between May 2019 and March 2021 to a Médecins Sans Frontières (MSF)-supported AHD inpatient unit in Bihar, India.

Methods

A retrospective analysis of routinely collected demographic, clinical and microbiological data. Antibacterial susceptibility testing was done by an accredited referral laboratory using the modified Kirby–Bauer disc diffusion method.

Results

A total of 238 isolates from 577 patients were identified through culture testing. Patient median (IQR) age was 38 (31–45) years, and 75% were male. Predominant sample types included blood (600; 38%), urine (266; 17%) and sputum (178; 11%). Of the isolated bacteria, Escherichia coli (80; 13.9%) was the most prevalent, followed by Klebsiella pneumonia (54; 9.4%), Pseudomonas aeruginosa (22; 3.8%), Klebsiella oxytoca (10; 1.7%), Proteus mirabilis (9; 1.6%), and Acinetobacter baumannii (7; 1.2%). The resistance pattern showed that most bacterial isolates were highly resistant to commonly prescribed antibiotics such as third-generation cephalosporins, fluoroquinolones and co-trimoxazole. Most pathogens were moderately resistant to antibiotics from the WHO Watch group, such as meropenem and piperacillin/tazobactam. In contrast, isolates were more susceptible to aminoglycosides, such as amikacin, gentamicin and nitrofurantoin.

Conclusions

In Bihar, inpatients with AHD displayed a concerning array of antibiotic-resistant infections. This study provides a starting point from which further work on antimicrobial resistance in this vulnerable cohort of patients can be conducted.
Barriers and facilitators to the implementation of family cancer history collection tools in oncology clinical practices
Authors: Allen Caitlin G , Neil Grace , Halbert Chanita Hughes , Sterba Katherine R , Nietert Paul J , Welch Brandon , Lenert Leslie
Published: January 2024

Introduction

This study aimed to identify barriers and facilitators to the implementation of family cancer history (FCH) collection tools in clinical practices and community settings by assessing clinicians’ perceptions of implementing a chatbot interface to collect FCH information and provide personalized results to patients and providers.

Objectives

By identifying design and implementation features that facilitate tool adoption and integration into clinical workflows, this study can inform future FCH tool development and adoption in healthcare settings.

Materials and methods

Quantitative data were collected using survey to evaluate the implementation outcomes of acceptability, adoption, appropriateness, feasibility, and sustainability of the chatbot tool for collecting FCH. Semistructured interviews were conducted to gather qualitative data on respondents' experiences using the tool and recommendations for enhancements.

Results

We completed data collection with 19 providers (n = 9, 47%), clinical staff (n = 5, 26%), administrators (n = 4, 21%), and other staff (n = 1, 5%) affiliated with the NCI Community Oncology Research Program. FCH was systematically collected using a wide range of tools at sites, with information being inserted into the patient’s medical record. Participants found the chatbot tool to be highly acceptable, with the tool aligning with existing workflows, and were open to adopting the tool into their practice.

Discussion and conclusions

We further the evidence base about the appropriateness of scripted chatbots to support FCH collection. Although the tool had strong support, the varying clinical workflows across clinic sites necessitate that future FCH tool development accommodates customizable implementation strategies. Implementation support is necessary to overcome technical and logistical barriers to enhance the uptake of FCH tools in clinical practices and community settings.
Screening in Women With BRCA Mutations Revisited
Authors: Greenwood Heather I , Dodelzon Katerina
Published: January 2024

Patients with BRCA1 or BRCA2 gene mutations are at high risk for the development of breast cancer. This article reviews the current evidence for breast cancer screening of patients with BRCA1 or BRCA2 pathogenic gene mutations if they have not undergone prophylactic mastectomy. It will review the current evidence-based imaging recommendations for different modalities and ages of screening initiation in screening this patient population at high risk. Special considerations in transgender BRCA1 and BRCA2 mutation carriers are also discussed.
Collagen mutation and age contribute to differential craniofacial phenotypes in mouse models of osteogenesis imperfecta
Authors: Sung Hsiao H , Spresser Wyatt J , Hoffmann Joseph P , Dai Zongrui , Van der Kraan Peter M , Caird Michelle S , Davidson Esmeralda Blaney , Kozloff Kenneth M
Published: January 2024

Craniofacial and dentoalveolar abnormalities are present in all types of osteogenesis imperfecta (OI). Mouse models of the disorder are critical to understand these abnormalities and underlying OI pathogenesis. Previous studies on severely affected OI mice report a broad spectrum of craniofacial phenotypes, exhibiting some similarities to the human disorder. The Brtl/+ and G610c/+ are moderately severe and mild-type IV OI, respectively. Little is known about the aging effects on the craniofacial bones of these models and their homology to human OI. This study aimed to analyze the Brtl/+ and G610c/+ craniofacial morphometries during aging to establish suitability for further OI craniofacial bone intervention studies. We performed morphological measurements on the micro-CT-scanned heads of 3-wk-old, 3-mo-old, and 6-mo-old female Brtl/+ and G610c/+ mice. We observed that Brtl/+ skulls are shorter in length than WT (P < .05), whereas G610c/+ skulls are similar in length to their WT counterparts. The Brtl/+ mice exhibit alveolar bone with a porotic-like appearance that is not observed in G610c/+. As they age, Brtl/+ mice show severe bone resorption in both the maxilla and mandible (P < .05). By contrast, G610c/+ mice experience mandibular resorption consistently across all ages, but maxillary resorption is only evident at 6 mo (P < .05). Western blot shows high osteoclastic activities in the Brtl/+ maxilla. Both models exhibit delayed pre-functional eruptions of the third molars (P < .05), which are similar to those observed in some bisphosphonate-treated OI subjects. Our study shows that the Brtl/+ and G610c/+ mice display clear features found in type IV OI patients; both show age-related changes in the craniofacial growth phenotype. Therefore, understanding the craniofacial features of these models and how they age will allow us to select the most accurate mouse model, mouse age, and bone structure for the specific craniofacial bone treatment of differing OI groups.
18F-Sodium fluoride PET-CT visualizes disease activity in chronic nonbacterial osteitis in adults
Authors: Leerling Anne T , Smit Frits , Spӓth Zita , Cañete Ana Navas , de Geus-Oei Lioe-Fee , van de Burgt Alina , Dekkers Olaf M , van der Bruggen Wouter , Appelman-Dijkstra Natasha M , Vriens Dennis , Winter Elizabeth M
Published: January 2024

Chronic nonbacterial osteitis (CNO) is a rare disease spectrum, which lacks biomarkers for disease activity. Sodium fluoride-18 positron emission tomography/computed tomography ([18F]NaF-PET/CT) is a sensitive imaging tool for bone diseases and yields quantitative data on bone turnover. We evaluated the capacities of [18F]NaF-PET/CT to provide structural and functional assessment in adult CNO. A coss-sectional study was performed including 43 adult patients with CNO and 16 controls (patients referred for suspected, but not diagnosed with CNO) who underwent [18F]NaF-PET/CT at our expert clinic. Structural features were compared between patients and controls, and maximal standardized uptake values (SUVmax [g/mL]) were calculated for bone lesions, soft tissue/joint lesions, and reference bone. SUVmax was correlated with clinical disease activity in patients. Structural assessment revealed manubrial and costal sclerosis/hyperostosis and calcification of the costoclavicular ligament as typical features associated with CNO. SUVmax of CNO lesions was higher compared with in-patient reference bone (mean paired difference: 11.4; 95% CI: 9.4–13.5; p < .001) and controls (mean difference: 12.4; 95%CI: 9.1–15.8; p < .001). The highest SUVmax values were found in soft tissue and joint areas such as the costoclavicular ligament and manubriosternal joint, and these correlated with erythrocyte sedimentation rate in patients (correlation coefficient: 0.546; p < .002). Our data suggest that [18F]NaF-PET/CT is a promising imaging tool for adult CNO, allowing for detailed structural evaluation of its typical bone, soft-tissue, and joint features. At the same time, [18F]NaF-PET/CT yields quantitative bone remodeling data that represent the pathologically increased bone turnover and the process of new bone formation. Further studies should investigate the application of quantified [18F]NaF uptake as a novel biomarker for disease activity in CNO, and its utility to steer clinical decision making.
Agricultural issues with climate change—case studies with 3 soybean pests: Johnsongrass, kudzu bug, and charcoal rot
Authors: Carley Danesha Seth , Cook Jennifer , Emerine Sherrie
Published: January 2024

Agricultural production and crop yields are threatened around the world by the emergence and spread of agronomical pests, including diseases, insects, and weeds. Due to changes in precipitation, carbon dioxide levels, and warming temperatures being experienced throughout most of the world, new challenges are emerging for pest management in virtually all major cropping systems. While precise environmental impacts due to climate change are impossible to predict, they will require innovative and new solutions for pest management. In this article, we explore the challenges of 3 problem pest species with soybean: Johnsongrass, kudzu bug, and charcoal rot. Understanding pest responses to climate change is vital for better understanding the new agricultural innovations that will be required to manage them in the future.
Discontinuation of Contact Precautions for Methicillin-resistant Staphylococcus aureus in a Pediatric Healthcare System
Authors: Most Zachary M , Phillips Bethany , Sebert Michael E
Published: January 2024

Background

Many hospitals caring for adult patients have discontinued the requirement for contact precautions (CP) for patients with methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization without reported negative effects. It is not clear whether this experience can be extrapolated to pediatric facilities.

Methods

CP for MRSA were discontinued in all locations except the neonatal intensive care unit at a 3-hospital pediatric healthcare system in September 2019. All hospitalized patients underwent surveillance for LabID healthcare facility-onset MRSA infections. Analysis was done using interrupted time series (ITS) from September 2017 through August 2023 and aggregate before-and-after rate ratios.

Results

There were 234 incident healthcare facility-onset MRSA infections during 766 020 patient days of surveillance. After discontinuation of CP for MRSA there was no change in the ITS slope (0.06, 95% CI: −0.35 to 0.47, P = .78) or intercept (0.21, 95% CI: −0.36 to 0.78, P = .47) of the LabID healthcare facility-onset MRSA infection incidence density rate. Additionally, there was no change in the aggregate incidence density rate of these MRSA LabID events (aggregate rate ratio = 0.98, 95% CI: 0.74 to 1.28). MRSA nasal colonization among patients being screened before cardiac surgery did not change (aggregate rate ratio = 0.94, 95% CI: 0.60 to 1.48). The prevalence rate of contact isolation days decreased by 14.0%.

Conclusions

Discontinuation of CP for pediatric patients with MRSA was not associated with increased MRSA infection over 4 years. Our experience supports considering discontinuation of CP for MRSA in similar pediatric healthcare settings in the context of good adherence to horizontal infection prevention measures.
Necessary conditions for the formation of filaments and star clusters in the cold neutral medium
Authors: Pillsworth Rachel , Pudritz Ralph E
Published: January 2024

Star formation takes place in filamentary molecular clouds which arise by physical processes that take place in the cold neutral medium (CNM). We address the necessary conditions for this diffuse (n ≈ 30 cm−3), cold (T ≈ 60 K), magnetized gas undergoing shock waves, and supersonic turbulence, to produce filamentary structures capable of fragmenting into cluster forming regions. Using ramses and a magnetized CNM environment as our initial conditions, we simulate a 0.5 kpc turbulent box to model a uniform gas with magnetic field strength of 7 μG, varying the 3D velocity dispersion via decaying turbulence. We use a surface density of 320 M⊙ pc−2, representative of the inner 4.0 kpc central molecular zone of the Milky Way and typical luminous galaxies. Filamentary molecular clouds are formed dynamically via shocks within a narrow range of velocity dispersions in the CNM of 5–10 km s−1 with a preferred value at 8 km s−1. Cluster sink particles appear in filaments which exceed their critical line mass, occurring optimally for velocity dispersions of 8 km s−1. Tracking the evolution of magnetic fields, we find that they lead to double the dense star-forming gas than in purely hydro runs. Perpendicular orientations between magnetic field and filaments can increase the accretion rates onto filaments and hence their line masses. Because magnetic fields help support gas, magnetohydrodynamic runs result in average temperatures an order of magnitude higher than unmagnetized counterparts. Finally, we find magnetic fields delay the onset of cluster formation by ∝ 0.4 Myr.
Reappraisal of the DNA phosphorothioate modification machinery: uncovering neglected functional modalities and identification of new counter-invader defense systems
Authors: Rakesh Siuli , Aravind L , Krishnan Arunkumar
Published: January 2024

The DndABCDE systems catalysing the unusual phosphorothioate (PT) DNA backbone modification, and the DndFGH systems, which restrict invasive DNA, have enigmatic and paradoxical features. Using comparative genomics and sequence-structure analyses, we show that the DndABCDE module is commonly functionally decoupled from the DndFGH module. However, the modification gene-neighborhoods encode other nucleases, potentially acting as the actual restriction components or suicide effectors limiting propagation of the selfish elements. The modification module's core consists of a coevolving gene-pair encoding the DNA-scanning apparatus – a DndD/CxC-clade ABC ATPase and DndE with two ribbon-helix-helix (MetJ/Arc) DNA-binding domains. Diversification of DndE’s DNA-binding interface suggests a multiplicity of target specificities. Additionally, many systems feature DNA cytosine methylase genes instead of PT modification, indicating the DndDE core can recruit other nucleobase modifications. We show that DndFGH is a distinct counter-invader system with several previously uncharacterized domains, including a nucleotide kinase. These likely trigger its restriction endonuclease domain in response to multiple stimuli, like nucleotides, while blocking protective modifications by invader methylases. Remarkably, different DndH variants contain a HerA/FtsK ATPase domain acquired from multiple sources, including cellular genome-segregation systems and mobile elements. Thus, we uncovered novel HerA/FtsK-dependent defense systems that might intercept invasive DNA during replication, conjugation, or packaging.
THUMPD2 catalyzes the N2-methylation of U6 snRNA of the spliceosome catalytic center and regulates pre-mRNA splicing and retinal degeneration
Authors: Yang Wen-Qing , Ge Jian-Yang , Zhang Xiaofeng , Zhu Wen-Yu , Lin Lin , Shi Yigong , Xu Beisi , Liu Ru-Juan
Published: January 2024

The mechanisms by which the relatively conserved spliceosome manages the enormously large number of splicing events that occur in humans (∼200 000 versus ∼300 in yeast) are poorly understood. Here, we show deposition of one RNA modification-N2-methylguanosine (m2G) on the G72 of U6 snRNA (the catalytic center of the spliceosome) promotes efficient pre-mRNA splicing activity in human cells. This modification was identified to be conserved among vertebrates. Further, THUMPD2 was demonstrated as the methyltransferase responsible for U6 m2G72 by explicitly recognizing the U6-specific sequences and structural elements. The knock-out of THUMPD2 eliminated U6 m2G72 and impaired the pre-mRNA splicing activity, resulting in thousands of changed alternative splicing events of endogenous pre-mRNAs in human cells. Notably, the aberrantly spliced pre-mRNA population elicited the nonsense-mediated mRNA decay pathway. We further show that THUMPD2 was associated with age-related macular degeneration and retinal function. Our study thus demonstrates how an RNA epigenetic modification of the major spliceosome regulates global pre-mRNA splicing and impacts physiology and disease.
Predicting the spread of SARS-CoV-2 variants: An artificial intelligence enabled early detection
Authors: Levi Retsef , Zerhouni El Ghali , Altuvia Shoshy
Published: January 2024

During more than 3 years since its emergence, SARS-CoV-2 has shown great ability to mutate rapidly into diverse variants, some of which turned out to be very infectious and have spread throughout the world causing waves of infections. At this point, many countries have already experienced up to six waves of infections. Extensive academic work has focused on the development of models to predict the pandemic trajectory based on epidemiological data, but none has focused on predicting variant-specific spread. Moreover, important scientific literature analyzes the genetic evolution of SARS-CoV-2 variants and how it might functionally affect their infectivity. However, genetic attributes have not yet been incorporated into existing epidemiological modeling that aims to capture infection trajectory. Thus, this study leverages variant-specific genetic characteristics together with epidemiological information to systematically predict the future spread trajectory of newly detected variants. The study describes the analysis of 9.0 million SARS-CoV-2 genetic sequences in 30 countries and identifies temporal characteristic patterns of SARS-CoV-2 variants that caused significant infection waves. Using this descriptive analysis, a machine-learning-enabled risk assessment model has been developed to predict, as early as 1 week after their first detection, which variants are likely to constitute the new wave of infections in the following 3 months. The model’s out-of-sample area under the curve (AUC) is 86.3% for predictions after 1 week and 90.8% for predictions after 2 weeks. The methodology described in this paper could contribute more broadly to the development of improved predictive models for variants of other infectious viruses.
Slowly but surely: Exposure of communities and infrastructure to subsidence on the US east coast
Authors: Ohenhen Leonard O , Shirzaei Manoochehr , Barnard Patrick L
Published: January 2024

Coastal communities are vulnerable to multihazards, which are exacerbated by land subsidence. On the US east coast, the high density of population and assets amplifies the region's exposure to coastal hazards. We utilized measurements of vertical land motion rates obtained from analysis of radar datasets to evaluate the subsidence-hazard exposure to population, assets, and infrastructure systems/facilities along the US east coast. Here, we show that 2,000 to 74,000 km2 land area, 1.2 to 14 million people, 476,000 to 6.3 million properties, and >50% of infrastructures in major cities such as New York, Baltimore, and Norfolk are exposed to subsidence rates between 1 and 2 mm per year. Additionally, our analysis indicates a notable trend: as subsidence rates increase, the extent of area exposed to these hazards correspondingly decreases. Our analysis has far-reaching implications for community and infrastructure resilience planning, emphasizing the need for a targeted approach in transitioning from reactive to proactive hazard mitigation strategies in the era of climate change.
GASZ self-interaction clusters mitochondria into the intermitochondrial cement for proper germ cell development
Authors: Miao Junru , Wang Chuanyun , Chen Wei , Wang Yongsheng , Kakasani Shalin , Wang Yuan
Published: January 2024

Mitochondrial features and activities vary in a cell type- and developmental stage-dependent manner to critically impact cell function and lineage development. Particularly in male germ cells, mitochondria are uniquely clustered into intermitochondrial cement (IMC), an electron-dense granule in the cytoplasm to support proper spermatogenesis. But it remains puzzling how mitochondria assemble into such a stable structure as IMC without limiting membrane during development. Here, we showed that GASZ (germ cell-specific, ankyrin repeat, SAM and basic leucine zipper domain containing protein), a mitochondrion-localized germ cell-specific protein, self-interacted with each other to cluster mitochondria and maintain protein stability for IMC assembling. When the self-interaction of GASZ was disrupted by either deleting its critical interaction motif or using a blocking peptide, the IMC structure was destabilized, which in turn led to impaired spermatogenesis. Notably, the blocked spermatogenesis was reversible once GASZ self-interaction was recovered. Our findings thus reveal a critical mechanism by which mitochondrion-based granules are properly assembled to support germ cell development while providing an alternative strategy for developing nonhormonal male contraceptives by targeting IMC protein interactions.
COVID-19 perturbation on US air quality and human health impact assessment
Authors: He Jian , Harkins Colin , O’Dell Katelyn , Li Meng , Francoeur Colby , Aikin Kenneth C , Anenberg Susan , Baker Barry , Brown Steven S , Coggon Matthew M , Frost Gregory J , Gilman Jessica B , Kondragunta Shobha , Lamplugh Aaron , Lyu Congmeng , Moon Zachary , Pierce Bradley R , Schwantes Rebecca H , Stockwell Chelsea E , Warneke Carsten , Yang Kai , Nowlan Caroline R , González Abad Gonzalo , McDonald Brian C
Published: January 2024

The COVID-19 stay-at-home orders issued in the United States caused significant reductions in traffic and economic activities. To understand the pandemic's perturbations on US emissions and impacts on urban air quality, we developed near-real-time bottom-up emission inventories based on publicly available energy and economic datasets, simulated the emission changes in a chemical transport model, and evaluated air quality impacts against various observations. The COVID-19 pandemic affected US emissions across broad-based energy and economic sectors and the impacts persisted to 2021. Compared with 2019 business-as-usual emission scenario, COVID-19 perturbations resulted in annual decreases of 10–15% in emissions of ozone (O3) and fine particle (PM2.5) gas-phase precursors, which are about two to four times larger than long-term annual trends during 2010–2019. While significant COVID-induced reductions in transportation and industrial activities, particularly in April–June 2020, resulted in overall national decreases in air pollutants, meteorological variability across the nation led to local increases or decreases of air pollutants, and mixed air quality changes across the United States between 2019 and 2020. Over a full year (April 2020 to March 2021), COVID-induced emission reductions led to 3–4% decreases in national population-weighted annual fourth maximum of daily maximum 8-h average O3 and annual PM2.5. Assuming these emission reductions could be maintained in the future, the result would be a 4–5% decrease in premature mortality attributable to ambient air pollution, suggesting that continued efforts to mitigate gaseous pollutants from anthropogenic sources can further protect human health from air pollution in the future.
Infection of tumor cells with Salmonella typhimurium mimics immunogenic cell death and elicits tumor-specific immune responses
Authors: Horiuchi Yutaka , Nakamura Akihiro , Imai Takashi , Murakami Takashi
Published: January 2024

Some properties of Salmonella-infected cells overlap with immunogenic cell death. In this study, we demonstrated that intracellular infection of melanoma with Salmonella typhimurium induced high immunogenicity in melanoma cells, leading to antitumor effects with melanoma-antigen-specific T-cell responses. Murine B16F10 melanoma cells were infected with tdTomato-expressing attenuated S. typhimurium (VNP20009; VNP-tdT), triggering massive cell vacuolization. VNP-tdT-infected B16F10 cells were phagocytosed efficiently, which induced the activation of antigen-presenting cells with CD86 expression in vitro. Subcutaneous coimplantation of uninfected and VNP-tdT-infected B16F10 cells into C57BL/6 mice significantly suppressed tumor growth compared with the implantation of uninfected B16F10 cells alone. Inoculation of mice with VNP-tdT-infected B16F10 cells elicited the proliferation of melanoma-antigen (gp100)-specific T cells, and it protected the mice from the second tumor challenge of uninfected B16F10 cells. These results suggest that Salmonella-infected tumor cells acquire effective adjuvanticity, leading to ideal antitumor immune responses.
Effect of chronic intermittent hypoxia on ocular and intraoral mechanical allodynia mediated via the calcitonin gene-related peptide in a rat
Authors: Katagiri Ayano , Kishimoto Saki , Okamoto Yoshie , Yamada Masaharu , Niwa Hitoshi , Bereiter David A , Kato Takafumi
Published: January 2024

Study Objectives

Obstructive sleep apnea, a significant hypoxic condition, may exacerbate several orofacial pain conditions. The study aims to define the involvement of calcitonin gene-related peptide (CGRP) in peripheral and central sensitization and in evoking orofacial mechanical allodynia under chronic intermittent hypoxia (CIH).

Methods

Male rats were exposed to CIH. Orofacial mechanical allodynia was assessed using the eyeblink test and the two-bottle preference drinking test. The CGRP-immunoreactive neurons in the trigeminal ganglion (TG), CGRP-positive primary afferents projecting to laminae I–II of the trigeminal spinal subnucleus caudalis (Vc), and neural responses in the second-order neurons of the Vc were determined by immunohistochemistry. CGRP receptor antagonist was administrated in the TG.

Results

CIH-induced ocular and intraoral mechanical allodynia. CGRP-immunoreactive neurons and activated satellite glial cells (SGCs) were significantly increased in the TG and the number of cFos-immunoreactive cells in laminae I–II of the Vc were significantly higher in CIH rats compared to normoxic rats. Local administration of the CGRP receptor antagonist in the TG of CIH rats attenuated orofacial mechanical allodynia; the number of CGRP-immunoreactive neurons and activated SGCs in the TG, and the density of CGRP-positive primary afferent terminals and the number of cFos-immunoreactive cells in laminae I–II of the Vc were significantly lower compared to vehicle-administrated CIH rats.

Conclusions

An increase in CGRP in the TG induced by CIH, as well as orofacial mechanical allodynia and central sensitization of second-order neurons in the Vc, supported the notion that CGRP plays a critical role in CIH-induced orofacial mechanical allodynia.
Benchmarking current preslaughter management factors, welfare indicators, and meat quality outcomes at commercial fed cattle processing facilities in the United States
Authors: Davis Melissa K , Sullivan Paxton A , Hess Ann M , Nair Mahesh N , Mooney Daniel F , Edwards-Callaway Lily N
Published: January 2024

Preslaughter management factors and their impacts on cattle welfare and meat quality are well documented in current literature. However, certain management factors related to transportation and lairage are underrepresented. Benchmarking preslaughter management factors that can impact welfare and meat quality outcomes will allow the industry to identify areas for improvement. The objective of the current study was to benchmark preslaughter management factors for a nationwide sample of commercial fed cattle processing facilities. Five processing facilities in the West, Midwest, and Southwest regions of the United States were sampled from March 2021 to July 2022. Data were collected on a total of n = 637 slaughter lots representing n = 87,220 head of cattle. Variables of interest included general cattle characteristics, distance traveled to the plant, truck wait times to unload, environmental conditions, lairage density, and lairage duration. Additionally, mobility was scored using a four-point locomotion scale (one being normal, not lame, and four being extremely reluctant to move). Carcasses were also observed for bruising using the following scale: no bruises, bruises smaller or larger than a deck of cards, and having multiple bruises. Descriptive statistics were performed on the data at the lot and individual animal level. On average, cattle traveled 155.8 ± 209.6 km (mean ± SD) from the feedlot to the processing facility and waited 30.3 ± 39.7 min to unload. Once in lairage pens, cattle were held for 200.7 ± 195.0 min. The mean lairage stocking density was 3.1 ± 2.0 m2 per head. A majority of the cattle scored a mobility score of 1 (n = 77,645, 91.8%), 7.8% (n = 6,125) were scored as a two and the remaining less than one percent of cattle were scored as either a 3 or 4 (n = 265). Carcasses with bruises less than or equal to the size of a deck of cards (n = 22,672, 27.1%) were less frequent than bruises measuring greater than the size of a deck of cards (n = 34,427, 42.6%). Of carcasses that were bruised, 65.2% (n = 39,856) had multiple bruises of varying size. This baseline data on preslaughter management factors identifies opportunities for improvement in wait times, lairage densities, and factors that cause bruising. Future studies should explore the relationships between these factors and their impacts on welfare and meat quality, report the economic value of these outcomes, and explore industry acceptability and adoptability of optimal preslaughter management practices.
Shock and modified shock indices in predicting poisoning severity and outcomes in acute aluminum phosphide poisoned patients
Authors: Ghonem Mona M , Abdelnoor Amira A , Hodeib Aliaa A
Published: January 2024

Background

Severe refractory hypotension and cardiogenic shock are the main contributors to death in acute aluminum phosphide (ALP) poisoning. Shock index (SI) and modified shock index (MSI) are easily obtained parameters that reflect shock at an early stage.

Aim

This study aimed to evaluate the role of SI and MSI in the prediction of the severity and outcomes of acute ALP poisoned patients.

Patients and methods

This cross sectional study was conducted on patients admitted to Tanta University Poison Control Centre with acute ALP poisoning from April 2022 to March 2023. Socio-demographics and toxicological data were taken, findings of clinical examination and laboratory investigations were recoded, SI was calculated by dividing heart rate over systolic blood pressure, and MSI was obtained by dividing heart rate over mean arterial pressure. Poisoning severity was assessed using poisoning severity score (PSS). Patients were divided into groups according to intensive care unit (ICU) admission and mortality.

Results

The study enrolled 94 patients. The median values of SI and MSI were significantly higher in ICU-admitted patients and non-survivors rather than their comparable groups. Significant positive correlations were observed between each of SI and MSI and PSS. At cut-off >1.14, SI conveyed fair performance to predict ICU admission and mortality (AUC = 0.710 and 0.739, respectively). Similarly, MSI had fair performance to predict ICU admission (AUC = 0.731) and mortality (AUC = 0.744) at cut-off >1.47 and >1.5, respectively.

Conclusion

Both SI and MSI could be considered simple bedside adjuncts to predict ICU admission and mortality in acute ALP poisoning.