bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of sEH inhibition on the eicosanoid and cytokine storms in SARS‐CoV‐2‐infected mice
Authors: Edin Matthew L. , Gruzdev Artiom , Graves Joan P. , Lih Fred B. , Morisseau Christophe , Ward James M. , Hammock Bruce D. , Bosio Catharine M. , Zeldin Darryl C.
Published: May 2024

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection involves an initial viral infection phase followed by a host‐response phase that includes an eicosanoid and cytokine storm, lung inflammation and respiratory failure. While vaccination and early anti‐viral therapies are effective in preventing or limiting the pathogenic host response, this latter phase is poorly understood with no highly effective treatment options. Inhibitors of soluble epoxide hydrolase (sEH) increase levels of anti‐inflammatory molecules called epoxyeicosatrienoic acids (EETs). This study aimed to investigate the impact of sEH inhibition on the host response to SARS‐CoV‐2 infection in a mouse model with human angiotensin‐converting enzyme 2 (ACE2) expression. Mice were infected with SARS‐CoV‐2 and treated with either vehicle or the sEH inhibitor 1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl) urea (TPPU). At day 5 post‐infection, SARS‐CoV‐2 induced weight loss, clinical signs, a cytokine storm, an eicosanoid storm, and severe lung inflammation with ~50% mortality on days 6–8 post‐infection. SARS‐CoV‐2 infection induced lung expression of phospholipase A2 (PLA2), cyclooxygenase (COX) and lipoxygenase (LOX) pathway genes, while suppressing expression of most cytochrome P450 genes. Treatment with the sEH inhibitor TPPU delayed weight loss but did not alter clinical signs, lung cytokine expression or overall survival of infected mice. Interestingly, TPPU treatment significantly reversed the eicosanoid storm and attenuated viral‐induced elevation of 39 fatty acids and oxylipins from COX, LOX and P450 pathways, which suggests the effects at the level of PLA2 activation. The suppression of the eicosanoid storm by TPPU without corresponding changes in lung cytokines, lung inflammation or mortality reveals a surprising dissociation between systemic oxylipin and cytokine signaling pathways during SARS‐CoV‐2 infection and suggests that the cytokine storm is primarily responsible for morbidity and mortality in this animal model.
Serum albumin exposure enhances cell invasiveness and paclitaxel resistance in human neuroblastoma cells, with attenuation by valeriana‐type iridoid glycosides
Authors: Uprety Ajay , Ngo Trung Huy , Prajapati Sanjaya , Joshi Shambhu , Nam Joo‐Won , Kim Soo Young
Published: May 2024

Neuroblastoma, a prevalent extracranial solid tumor in children, arises from undifferentiated nerve cells. While tumor vasculature, often characterized by increased permeability, influences metastasis and recurrence, the direct impact of blood‐borne molecules on tumor progression remains unclear. In the present study, we focused on the effect of exposure to albumin, one of the most abundant proteins in the serum, on human neuroblastoma cells. Albumin exposure elevated oxidative stress and led to mitochondria dysfunction via the activation of TGFβ and PI3K pathways, accompanied by an increase in the metastatic and invasive properties of neuroblastoma cells. Proteins relevant to the induction of autophagy were upregulated in response to prolonged albumin exposure. Additionally, pre‐exposure to albumin before treatment resulted in increased resistance to paclitaxel. Two valeriana‐type iridoid glycosides, patrisophoroside and patrinalloside, recently isolated from Nardostachys jatamansi significantly mitigated the effect of albumin on oxidative stress, cell invasiveness, and chemoresistance. These findings illuminate the potential role of blood‐borne molecules, such as albumin, in the progression and metastasis of neuroblastoma, as well as the possible therapeutic implications of valeriana‐type iridoid glycosides in anti‐cancer treatment.
Perceptions of Overdose Response Hotlines and Phone Application Services Among Women and Gender-diverse Individuals Who Use Drugs in Canada: A Qualitative Study
Authors: Lee Amanda , Jafri Farah , Viste Dylan , Seo Boogyung , Skiber Darci , Medwid Marguerite , Ghosh S. Monty
Published: May 2024

Objectives

In 2021, opioid-related deaths have increased by 96% and continue to be higher than prepandemic levels. In particular, women and gender-diverse individuals face numerous challenges when assessing harm reduction supports, including physical supervised consumption sites, compared with male counterparts. Mobile overdose response services (MORSs) including overdose response hotlines and phone-based overdose response applications are novel virtual overdose response technologies that may help mitigate this issue. This study aims to explore how women and gender-diverse individuals engage with and perceive these services.

Methods

A qualitative study using grounded theory was conducted. Using existing peer networks and purposive and snowball sampling between March and July 2023, 19 semistructured interviews were conducted with women and gender-diverse individuals in Canada who have lived experience using substances. NVivo was used for thematic analysis, which continued until saturation was reached.

Results

The interviews elucidated the following 5 themes: Overdose response hotlines and applications were generally preferred over supervised consumption sites due to (1) perceived gender-based safety; (2) better accommodation for mothers concerned with stigma, childcare, and child welfare systems; and (3) eased accessibility for those involved in sex work. It was also noted that (4) judgment-free spaces and trauma-informed care provided by staff with lived experiences were invaluable, and (5) decriminalization of illicit substances will encourage uptake of these harm reduction services.

Conclusion

This study found that women and gender-diverse individuals felt positively toward overdose response hotlines and applications with the potential to fill a need in providing harm reduction services that create feelings of safety, support roles of motherhood and sex work, and generate nonstigmatizing spaces.
Immediate Postoperative Change in the Upper Instrumented Screw-Vertebra Angle is a Predictor for Proximal Junctional Kyphosis and Failure
Authors: Cetik Riza M. , Glassman Steven D. , Dimar John R. , Crawford Charles H. , Gum Jeffrey L. , Smith Jensen , McGrath Nicole , Carreon Leah Y.
Published: May 2024

Study Design.

Retrospective review.

Objectives.

To determine if change in position of upper instrumented vertebral (UIV) screw between intraoperative prone and immediate postoperative standing radiographs is a predictor for proximal junctional kyphosis or failure (PJK/PJF).

Summary of Background Data.

Cranially directed UIV screws on postoperative radiographs have been found to be associated with PJK. Change in the screw position between intraoperative and immediate postoperative radiographs has not been studied.

Materials and Methods.

Patients with posterior fusion greater than or equal to three levels and UIV at or distal to T8, and minimum two-year follow-up were identified from a single-center database. Primary outcomes were radiographic PJK/PJF or revision for PJK/PJF. Demographic, surgical, and radiographic variables, including intraoperative screw-vertebra (S-V) angle, change in S-V angle, direction of UIV screw (cranial-neutral-caudal), and rod-vertebra (R-V) angle were collected.

Results.

Totally, 143 cases from 110 patients were included with a mean age of 62.9 years and a follow-up of 3.5 years. Fifty-four (38%) cases developed PJK/PJF, of whom 30 required a revision. Mean S-V angle was -0.9°±5.5° intraoperative and -2.8°±5.5° postoperative. The group with PJK/PJF had a mean S-V angle change of -2.5°±2.4 while the rest had a change of -1.0°±1.6 (P=0.010). When the change in S-V angle was <5°, 33% developed PJK, this increased to 80% when it was ≥5° (P=0.001). Revision for PJK/PJF increased from 16% to 60% when S-V angle changed ≥5° (P=0.001). Regression analysis showed S-V angle change as a significant risk factor for PJK/PJF (P=0.047, OR=1.58) and for revision due to PJK/PJF (P=0.009, OR=2.21).

Conclusions.

Change in the S-V angle from intraoperative prone to immediate postoperative standing radiograph is a strong predictor for PJK/PJF and for revision. For each degree of S-V angle change, odds of revision for PJK/PJF increases by x2.2. A change of 5° should alert the surgeon to the likely development of PJK/PJF requiring revision.

Level of Evidence.

Level II.
Comparison of Central and Peripheral Arterial Blood Pressure Gradients in Critically Ill Patients: A Systematic Review and Meta-Analysis
Authors: Hasegawa Daisuke , Sato Ryota , Duggal Abhijit , Schleicher Mary , Nishida Kazuki , Khanna Ashish K. , Dugar Siddharth
Published: May 2024

OBJECTIVES:

Measurement of blood pressure taken from different anatomical sites, are often perceived as interchangeable, despite them representing different parts of the systemic circulation. We aimed to perform a systematic review and meta-analysis on blood pressure differences between central and peripheral arterial cannulation in critically ill patients.

DATA SOURCES:

We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase from inception to December 26, 2023, using Medical Subject Headings (MeSH) terms and keywords.

STUDY SELECTION:

Observation study of adult patients in ICUs and operating rooms who underwent simultaneous central (femoral, axillary, or subclavian artery) and peripheral (radial, brachial, or dorsalis pedis artery) arterial catheter placement in ICUs and operating rooms.

DATA EXTRACTION:

We screened and extracted studies independently and in duplicate. We assessed risk of bias using the revised Quality Assessment for Studies of Diagnostic Accuracy tool.

DATA SYNTHESIS:

Twenty-four studies that enrolled 1598 patients in total were included. Central pressures (mean arterial pressure [MAP] and systolic blood pressure [SBP]) were found to be significantly higher than their peripheral counterparts, with mean gradients of 3.5 and 8.0 mm Hg, respectively. However, there was no statistically significant difference in central or peripheral diastolic blood pressure (DBP). Subgroup analysis further highlighted a higher MAP gradient during the on-cardiopulmonary bypass stage of cardiac surgery, reperfusion stage of liver transplant, and in nonsurgical critically ill patients. SBP or DBP gradient did not demonstrate any subgroup specific changes.

CONCLUSIONS:

SBP and MAP obtained by central arterial cannulation were higher than peripheral arterial cannulation; however, clinical implication of a difference of 8.0 mm Hg in SBP and 3.5 mm Hg in MAP remains unclear. Our current clinical practices preferring peripheral arterial lines need not change.
Information Management in Hospital Unit Daily Operations
Authors: von Gerich Hanna , Peltonen Laura-Maria
Published: May 2024

Operations management of a hospital unit is a shared activity involving nursing and medical professionals, characterized by suddenly changing situations, constant interruptions, and ad hoc decision-making. Previous studies have explored the informational needs affecting decision-making, but only limited information has been collected regarding factors affecting information management related to the daily operations of hospital units. The aim of this study was to describe the experiences of nursing and medical professionals of information management in the daily operations of hospital units. This qualitative study consists of interviews following the critical incidence technique. Twenty-six nurses and eight physicians working in operational leadership roles in hospital units were interviewed, and the data were subjected to thematic analysis. The data analysis showed that strengths of current systems were organizational operational procedures, general instruments supporting information management, and a digital operations dashboard, whereas opportunities for improvement included the information architecture, quality of information, and technology use. The study findings highlight that despite several decades of efforts to provide solutions to support information management in hospital daily operations, further measures need to be taken in developing and implementing information systems with user-centered strategies and systematic approaches to better support healthcare professionals.
Study of the relationship between the severity of posterior capsular opacification detected by objective detection techniques and visual acuity
Authors: Song Ziyue , Chen Zhigang , Li Caixin , Li Yanting , Liu Yueqi , Lu Peirong
Published: May 2024

Purpose:

To explore the severity of posterior capsule opacification (PCO) using objective detection techniques and its relationship with visual acuity.

Setting:

The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

Design:

Prospective cohort study.

Methods:

All patients underwent slitlamp examination, intraocular pressure (IOP) measurement, and corrected distance visual acuity (CDVA) testing before Nd:YAG laser capsulotomy, and examination, after fully dilated, with: IOLMaster 700, optical coherence tomography (OCT), Sirius Topographer (CSO) anterior segment analysis, and color fundus photography (CFP). CDVA and IOP were taken post treatment. Thickness and density of the posterior capsule, CFP quality (CFPQ) and OCT signal strength (OCTSS) were recorded. Analysis used Spearman correlation, heatmaps, and receiver operating characteristic curves.

Results:

83 eyes in 78 patients were included in this study. Spearman correlation analysis revealed correlations between pretreatment CDVA and IOLMaster 700 PCO thickness (MT), IOLMaster 700 cumulative effect (MCE), Sirius PCO thickness (ST), Sirius maximum density (SMD), Sirius cumulative effect (SCE), OCTSS, and CFPQ (correlation coefficients were 0.500, 0.484, 0.465, −0.256, 0.317, −0.442, −0.412, all P < .05). The improvement of vision acuity (ImpVA) showed correlations with MT, MCE, ST, SCE, OCTSS, and CFPQ (correlation coefficients were −0.452, −0.471, −0.346, −0.278, 0.320, 0.381, all P < .05). For ImpVA, the predictive ability of IOLMaster 700 was superior to Sirius, and the joint model was significantly better than single factors.

Conclusions:

Posterior capsule thickness and cumulative effect were reliable indicators for evaluating PCO. Compared with Sirius, the IOLMaster 700 demonstrated superior predictive ability and higher correlation.
Harlem Health Advocacy Partners: A Local Health Department’s Place-Based Community Health Worker Program
Authors: Dannefer Rachel , Seidl Lois , Drackett Elizabeth , Wohlman Adam , Campbell Safiya , Herrera Diana , Sealy Carrie , Perez Veronica , Mata Andrea , Pinzon Juan , Islam Nadia , Thorpe Lorna E. , Brown-Dudley La’Shawn , Manyindo Noel
Published: May 2024

In January 2015, the New York City Department of Health and Mental Hygiene launched Harlem Health Advocacy Partners (HHAP), a place-based initiative to demonstrate the capacity of a CHW workforce to improve the health of residents of public housing. The long-term goal of HHAP is to improve the population health of residents of public housing in East and Central Harlem and to close racial gaps in health and social outcomes. A variety of evaluation approaches have been used to assess the initiative. This paper describes the HHAP model and methods for evaluating the program.
Covid-19 Across Professions—Infection, Hospitalization, and Intensive Care Unit Patterns in a Swedish County
Authors: Månsson Jonas , Cajander Sara , Lidén Mats , Löfstedt Håkan , Westberg Håkan
Published: May 2024

Objective

The aim of the study was to study infection, hospitalization, and admission to intensive care unit for COVID-19 in different occupations and pandemic waves in a Swedish county.

Methods

Individual registry data of infection and hospitalization were merged with occupational data in this cross-sectional study. Infected, hospital-, and intensive care unit-admission were analyzed by occupational groups.

Results

22,095 cases of COVID-19 from 21 February 2020 to 31 August 2022 were identified. Healthcare workers and others working in close physical proximity showed a higher rate of confirmed COVID-19 infections in all waves and higher risk for hospital admission early in the pandemic. Exposure to diseases and physical proximity played a decisive role.

Conclusions

Workers in close-contact occupations experienced a higher rate of confirmed infections throughout the pandemic and higher hospitalization rates in the first pandemic wave, suggesting a need for more effective initial safety measures in a future pandemic.
A review on legal issues of medical robots
Authors: Shentu Xiaoli
Published: May 2024

This paper examines the legal challenges associated with medical robots, including their legal status, liability in cases of malpractice, and concerns over patient data privacy and security. And this paper scrutinizes China’s nuanced response to these dilemmas. An analysis of Chinese judicial practices and legislative actions reveals that current denial of legal personality to AI at this stage is commendable. To effectively control the financial risks associated with medical robots, there is an urgent need for clear guidelines on responsibility allocation for medical accidents involving medical robots, the implementation of strict data protection laws, and the strengthening of industry standards and regulations.
Better liver transplant outcomes by donor interventions?
Authors: Hessheimer Amelia J. , Flores Eva , Vengohechea Jordi , Fondevila Constantino
Published: May 2024

Purpose of review

Donor risk factors and events surrounding donation impact the quantity and quality of grafts generated to meet liver transplant waitlist demands. Donor interventions represent an opportunity to mitigate injury and risk factors within donors themselves. The purpose of this review is to describe issues to address among donation after brain death, donation after circulatory determination of death, and living donors directly, for the sake of optimizing relevant outcomes among donors and recipients.

Recent findings

Studies on donor management practices and high-level evidence supporting specific interventions are scarce. Nonetheless, for donation after brain death (DBD), critical care principles are employed to correct cardiocirculatory compromise, impaired tissue oxygenation and perfusion, and neurohormonal deficits. As well, certain treatments as well as marginally prolonging duration of brain death among otherwise stable donors may help improve posttransplant outcomes. In donation after circulatory determination of death (DCD), interventions are performed to limit warm ischemia and reverse its adverse effects. Finally, dietary and exercise programs have improved donation outcomes for both standard as well as overweight living donor (LD) candidates, while minimally invasive surgical techniques may offer improved outcomes among LD themselves.

Donor interventions represent means to improve liver transplant yield and outcomes of liver donors and grafts.
Romiplostim for Treatment of Children and Young Adults With Severe Aplastic Anemia and Myelodysplastic Syndrome
Authors: Sharathkumar Anjali , Carr Jamie , Claassen David , Syrbu Sergei , Bhagavathi Sharathkumar , Al-Huniti Ahmad , Modi Arunkumar , Bates Melissa , Mott Sarah L.
Published: May 2024

Thrombopoietin receptor agonists (TPO-RAs) induce trilineage hematopoiesis under conditions with acquired hematopoietic failure. We evaluated safety, tolerability, and preliminary efficacy of a TPO-RA, romiplostim (Nplate), with or without standard-of-care immunosuppressive therapy (±IST) for children (ages <21 y) with newly diagnosed and relapsed/refractory severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS). Data were collected from an observational study and a single arm interventional pilot study. The safety outcome was treatment-related adverse events (AEs). Efficacy was evaluated by complete hematopoietic response (CHR) at week 24. Romiplostim was commenced at 5 µg/kg/week, with dose escalation of 2.5 µg/kg/week (maximum, 20 µg/kg/dose) based on platelet response. Romiplostim was continued until CHR was observed. Ten subjects (SAA, 9 [IST, 4; without IST, 5]; MDS, 1) completed the study (median age: 9.2 y). Median romiplostim dose was 10 µg/kg/week (range: 5 to 17.5 µg/kg/week). The cumulative incidence of CHR was 70.4% (95% CI, 20.2%-92.6%). Among 21 AEs (Grade 1 to 3), 3 were attributed to romiplostim. At a median posttherapy follow-up of 10.9 months (range: 0.7 to 77.5), no clonal evolution, bone marrow fibrosis or mortality was reported. This proof-of-concept study provides data about short-term safety, tolerability, and preliminary efficacy of romiplostim (±IST) for treatment of pediatric SAA/MDS.
Advanced antibacterial materials for the prevention of nosocomial infections
Authors: Kong Chun , Wang Xuetong , Li Huipeng , Zhou Huan , Yang Lei
Published: May 2024

Nosocomial infections, as the most common adverse event in health care environments, have become an urgent global challenge. It is of great significance in solving nosocomial infections to improve patient survival rates and reduce the economic burden on patients. Antibacterial materials play a crucial role in the prevention and treatment of nosocomial infections. Since traditional antibacterial materials are not sufficient to satisfy the increasing clinical requirements, advanced antibacterial materials are widely developed in biomedical applications and hospital health fields, aiming at achieving more efficient, longer-lasting, and safer antimicrobial effects. This article outlines the construction strategies and mechanisms of advanced antibacterial materials, including bacterial adhesion prevention, release of antibacterial agents, contact-kill materials, and multistrategy-based sterilization. Meanwhile, the latest progress in advanced antibacterial materials in clinical departments and public environments is summarized and explored, including dressings, medical sutures, implants, bone cements, catheters, plastics products, ceramics, and fiber fabrics. Finally, the challenges and future directions for researches and translations of advanced antibacterial materials are discussed, providing comprehensive reference and guidance for the development of medical system and clinical applications.
Interactions Between Caregiving and Sex and the Antibody Response to COVID-19 Vaccination
Authors: Gallagher Stephen , Ryan Ruth , Cassidy Irene , Tang Wenyi , Whittaker Anna C.
Published: May 2024

Objective

Antibody response to vaccination is a powerful paradigm for studying the effects of chronic stress on immune function. In the present study, we used this paradigm to examine the interaction between caregiving (as a type of chronic stress) and sex on the antibody response to a single dose of a COVID-19 vaccination; recent research has called for examination of sex differences on health outcomes among family caregivers. A three-way interaction between caregiving, sex, and psychological distress was also examined.

Methods

COVID-19 antibody data were extracted from 165 caregivers (98 females) and 386 non-caregivers (244 females) from the UK’s Understanding Society COVID-19 study. Relevant sociodemographics, health and lifestyle, and distress variables were gathered as potential covariates.

Results

In a 2 × 2 ANOVA, we found that the interaction between caregiving and sex was significant; male caregivers had a lower antibody response to the vaccine compared to female caregivers (F(1,547), =24.82, p < .001, η
2
p = 0.043). Following adjustment, male caregivers had the lowest antibody response relative to all other groups. The three-way interaction model, controlling for covariates, was also significant (R
2 = 0.013, p = .049); the conditional effects for the three-way interaction revealed that male caregivers, compared to the other groups, had a lower antibody response at both low and medium levels of psychological distress.

Conclusion

This study found evidence of a three-way interaction between caregiving, sex, and distress on antibody response. Male caregivers had poorer antibody response to a single shot of the COVID-19 vaccination than female caregivers and male and female non-caregivers, and this was evident at low and medium levels of distress. Our findings will be discussed in relation to the caregiver and sex interactions during the pandemic.
The Common Carotid Artery in the Ultrasound Evaluation of Giant Cell Arteritis
Authors: Oshinsky Charles , Pollock P. Scott , Sacksen Ingeborg , Jernberg Elizabeth , Zierler R. Eugene , Bays Alison M.
Published: May 2024

Objectives

Vascular ultrasound is commonly used to diagnose giant cell arteritis (GCA). Most protocols include the temporal arteries and axillary arteries, but it is unclear which other arteries should be included. This study investigated whether inclusion of intima media thickness (IMT) of the common carotid artery (CCA) in the ultrasound evaluation of GCA improves the accuracy of the examination.

Methods

We formed a fast-track clinic to use ultrasound to rapidly evaluate patients with suspected GCA. In this cohort study, patients referred for new concern for GCA received a vascular ultrasound for GCA with the temporal arteries and branches, the axillary artery, and CCA.

Results

We compared 57 patients with GCA and 86 patients without GCA. Three patients with GCA had isolated positive CCA between 1 and 1.49 mm, and 21 patients without GCA had isolated positive CCA IMT. At the 1.5-mm CCA cutoff, 4 patients without GCA had positive isolated CCA, and 1 patient with GCA had a positive isolated CCA. The sensitivity of ultrasound when adding carotid arteries to temporal and axillary arteries was 84.21% and specificity 65.12% at an intima media thickness (IMT) cutoff of ≥1 mm and 80.70% and 87.21%, respectively, at a cutoff of ≥1.5 mm.

Conclusion

Measurement of the CCA IMT rarely contributed to the diagnosis of GCA and increased the rate of false-positive results. Our data suggest that the CCA should be excluded in the initial vascular artery ultrasound protocol for diagnosing GCA. If included, an IMT cutoff of higher than 1.0 mm should be used.
Enhancing Surgical Approach
Authors: Kim Tae Hyung , Kim Young Chul , Jeong Woo Shik , Choi Jong-Woo
Published: May 2024

Background

Innovative technologies with surgical navigation have been used for enhancing surgical accuracies for zygomaticomaxillary complex (ZMC) fractures and offers advantages in precision, accuracy, effectiveness, predictability, and symmetry improvement. Moreover, augmented reality (AR) navigation technology combines virtual reality, 3-dimensional (3D) reconstruction, and real-time interaction, making it ideal for bone tissue operations. Our study explored the usefulness and clinical efficacy of AR technology in intraoperative guidance for reducing ZMC fractures.

Methods

We retrospectively studied 35 patients with zygomatic complex fractures, comparing outcomes of AR-guided and conventional methods. Furthermore, the AR system provided real-time visualization and guidance. The evaluation included reduction accuracy using root mean square (RMS) value and symmetry analysis using a mirror image of 3D models. Results demonstrated the feasibility and effectiveness of the AR-guided method in improving outcomes and patient satisfaction.

Results

In 35 patients (25 males, 10 females), AR-guided (n = 19) and conventional (n = 16) approaches were compared. Age, sex, and fracture type exhibited no significant differences between groups. No complications occurred, and postoperative RMS error significantly decreased (P < 0.001). The AR group had a lower postoperative RMS error (P = 0.034).

Conclusions

Augmented reality-guided surgery improved accuracy and outcomes in zygomatic complex fractures. Real-time visualization enhanced precision during reduction and fixation. This innovative approach promises enhanced surgical accuracy and patient outcomes in craniofacial surgery.
Subnormothermic Oxygenated Machine Perfusion (24 h) in DCD Kidney Transplantation
Authors: Abraham Nader , Gao Qimeng , Kahan Riley , Alderete Isaac S. , Wang Bangchen , Howell David N. , Anwar Imran J. , Ladowski Joseph M. , Nakata Kentaro , Jarrett Ethan , Hlewicki Kendall , Cywinska Greta , Neill Ryan , Aardema Charles , Gerber David A. , Roy-Chaudhury Prabir , Hughes Benjamin A. , Hartwig Matthew G. , Barbas Andrew S.
Published: May 2024

Background.

Ex vivo kidney perfusion is an evolving platform that demonstrates promise in preserving and rehabilitating the kidney grafts. Despite this, there is little consensus on the optimal perfusion conditions. Hypothermic perfusion offers limited functional assessment, whereas normothermic perfusion requires a more complex mechanical system and perfusate. Subnormothermic machine perfusion (SNMP) has the potential to combine the advantages of both approaches but has undergone limited investigation. Therefore, the present study sought to determine the suitability of SNMP for extended kidney preservation.

Methods.

SNMP at 22–25 °C was performed on a portable device for 24 h with porcine kidneys. Graft assessment included measurement of mechanical parameters and biochemical analysis of the perfusate using point-of-care tests. To investigate the viability of kidneys preserved by SNMP, porcine kidney autotransplants were performed in a donation after circulatory death (DCD) model. SNMP was also compared with static cold storage (SCS). Finally, follow-up experiments were conducted in a subset of human kidneys to test the translational significance of findings in porcine kidneys.

Results.

In the perfusion-only cohort, porcine kidneys all displayed successful perfusion for 24 h by SNMP, evidenced by stable mechanical parameters and biological markers of graft function. Furthermore, in the transplant cohort, DCD grafts with 30 min of warm ischemic injury demonstrated superior posttransplant graft function when preserved by SNMP in comparison with SCS. Finally, human kidneys that underwent 24-h perfusion exhibited stable functional and biological parameters consistent with observations in porcine organs.

Conclusions.

These observations demonstrate the suitability and cross-species generalizability of subnormothermic machine perfusion to maintain stable kidney perfusion and provide foundational evidence for improved posttransplant graft function of DCD kidneys after SNMP compared with SCS.
Genomics and physiology of Catenibacillus, human gut bacteria capable of polyphenol C-deglycosylation and flavonoid degradation
Authors: Goris Tobias , Braune Annett
Published: May 2024

The genus Catenibacillus (family Lachnospiraceae, phylum Bacillota) includes only one cultivated species so far, Catenibacillus scindens, isolated from human faeces and capable of deglycosylating dietary polyphenols and degrading flavonoid aglycones. Another human intestinal Catenibacillus strain not taxonomically resolved at that time was recently genome-sequenced. We analysed the genome of this novel isolate, designated Catenibacillus decagia, and showed its ability to deglycosylate C-coupled flavone and xanthone glucosides and O-coupled flavonoid glycosides. Most of the resulting aglycones were further degraded to the corresponding phenolic acids. Including the recently sequenced genome of C. scindens and ten faecal metagenome-assembled genomes assigned to the genus Catenibacillus, we performed a comparative genome analysis and searched for genes encoding potential C-glycosidases and other polyphenol-converting enzymes. According to genome data and physiological characterization, the core metabolism of Catenibacillus strains is based on a fermentative lifestyle with butyrate production and hydrogen evolution. Both C. scindens and C. decagia encode a flavonoid O-glycosidase, a flavone reductase, a flavanone/flavanonol-cleaving reductase and a phloretin hydrolase. Several gene clusters encode enzymes similar to those of the flavonoid C-deglycosylation system of Dorea strain PUE (DgpBC), while separately located genes encode putative polyphenol-glucoside oxidases (DgpA) required for C-deglycosylation. The diversity of dgpA and dgpBC gene clusters might explain the broad C-glycoside substrate spectrum of C. scindens and C. decagia. The other Catenibacillus genomes encode only a few potential flavonoid-converting enzymes. Our results indicate that several Catenibacillus species are well-equipped to deglycosylate and degrade dietary plant polyphenols and might inhabit a corresponding, specific niche in the gut.
Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data
Authors: Sutcliffe Steven G. , Kraemer Susanne A. , Ellmen Isaac , Knapp Jennifer J. , Overton Alyssa K. , Nash Delaney , Nissimov Jozef I. , Charles Trevor C. , Dreifuss David , Topolsky Ivan , Baykal Pelin I. , Fuhrmann Lara , Jablonski Kim P. , Beerenwinkel Niko , Levy Joshua I. , Olabode Abayomi S. , Becker Devan G. , Gugan Gopi , Brintnell Erin , Poon Art F.Y. , Valieris Renan , Drummond Rodrigo D. , Defelicibus Alexandre , Dias-Neto Emmanuel , Rosales Rafael A. , Tojal da Silva Israel , Orfanou Aspasia , Psomopoulos Fotis , Pechlivanis Nikolaos , Pipes Lenore , Chen Zihao , Baaijens Jasmijn A. , Baym Michael , Shapiro B. Jesse
Published: May 2024

Wastewater-based surveillance (WBS) is an important epidemiological and public health tool for tracking pathogens across the scale of a building, neighbourhood, city, or region. WBS gained widespread adoption globally during the SARS-CoV-2 pandemic for estimating community infection levels by qPCR. Sequencing pathogen genes or genomes from wastewater adds information about pathogen genetic diversity, which can be used to identify viral lineages (including variants of concern) that are circulating in a local population. Capturing the genetic diversity by WBS sequencing is not trivial, as wastewater samples often contain a diverse mixture of viral lineages with real mutations and sequencing errors, which must be deconvoluted computationally from short sequencing reads. In this study we assess nine different computational tools that have recently been developed to address this challenge. We simulated 100 wastewater sequence samples consisting of SARS-CoV-2 BA.1, BA.2, and Delta lineages, in various mixtures, as well as a Delta–Omicron recombinant and a synthetic ‘novel’ lineage. Most tools performed well in identifying the true lineages present and estimating their relative abundances and were generally robust to variation in sequencing depth and read length. While many tools identified lineages present down to 1 % frequency, results were more reliable above a 5 % threshold. The presence of an unknown synthetic lineage, which represents an unclassified SARS-CoV-2 lineage, increases the error in relative abundance estimates of other lineages, but the magnitude of this effect was small for most tools. The tools also varied in how they labelled novel synthetic lineages and recombinants. While our simulated dataset represents just one of many possible use cases for these methods, we hope it helps users understand potential sources of error or bias in wastewater sequencing analysis and to appreciate the commonalities and differences across methods.
Use of Stem Cell-Derived Cardiomyocyte and Nasal Epithelium Models to Establish a Multi-Tissue Model Platform to Validate Repurposed Drugs Against SARS-CoV-2 Infection
Authors: Gödde Nathan J , O’Brien Carmel M , Vincan Elizabeth , Vashi Aditya , Olliff Stephanie , Tran Bang M , Waters Shafagh A , Goldie Sarah , van Vuren Petrus Jansen , Riddell Shane , Bruce Matthew P , Agarwal Vinti , Athan Eugene , Blasdell Kim R , Chahal Simran , Creek Darren J , Faheem  , Jain Hardik A , Kirkpatrick Carl M , Kumar Anupama , MacRaild Christopher A , Muzaffar-Ur-Rehman Mohammed , Sankaranarayanan Murugesan , Shah Rohan M , Styles Ian K , Tachedjian Mary , Trevaskis Natalie L , Singanallur Nagendrakumar B , McAuley Alexander J , Vasan Seshadri S
Published: May 2024

The novel coronavirus disease (COVID-19) and any future coronavirus outbreaks will require more affordable, effective and safe treatment options to complement current ones such asPaxlovid. Drug repurposing can be a promising approach if we are able to find a rapid, robust and reliable way to down-select and screen candidates usingin silicoandin vitroapproaches. With repurposed drugs, ex vivo models could offer a rigorous route to human clinical trials with less time invested into nonclinical animal (in vivo) studies. We have previously shown the value of commercially availableex vivo/3Dairway and alveolar tissue models, and this paper takes this further by developing and validating human nasal epithelial model and embryonic stem cells derived cardiomyocyte model. Five shortlisted candidates (fluvoxamine, everolimus, pyrimethamine, aprepitant and sirolimus) were successfully compared with three control drugs (remdesivir, molnupiravir, nirmatrelvir) when tested against key variants of the SARS-CoV-2 virus including Delta and Omicron, and we were able to reconfirm our earlier finding that fluvoxamine can induce antiviral efficacy in combination with other drugs. Scalability of this high-throughput screening approach has been demonstrated using a liquid handling robotic platform for future ‘Disease-X’ outbreaks.
A new GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release
Authors: Xia Xiju , Li Yulong
Published: May 2024

The co-existence and co-transmission of neuropeptides and small molecule neurotransmitters in the same neuron is a fundamental aspect of almost all neurons across various species. However, the differences regarding theirin vivospatiotemporal dynamics and underlying molecular regulation remain poorly understood. Here, we developed a GPCR-activation-based (GRAB) sensor for detecting short neuropeptide F (sNPF) with high sensitivity and spatiotemporal resolution. Furthermore, we explore the differences ofin vivodynamics and molecular regulation between sNPF and acetylcholine (ACh) from the same neurons. Interestingly, the release of sNPF and ACh shows different spatiotemporal dynamics. Notably, we found that distinct synaptotagmins (Syt) are involved in these two processes, as Syt7 and Sytα for sNPF release, while Syt1 for ACh release. Thus, this new GRAB sensor provides a powerful tool for studying neuropeptide release and providing new insights into the distinct release dynamics and molecular regulation between neuropeptides and small molecule neurotransmitters.
Discovery and binding site identification of a single-stranded DNA-binding protein that interacts with double-stranded DNA
Authors: Yao Wang , Yajie Tang , Zhihui Jiang , Lei Ma , Yiwen Liu , Sen Lin , Yaoyu Xu , Wenhui Zhang , Shaoting Weng
Published: May 2024

Scientists have conducted in-depth studies on single-stranded DNA (ssDNA) binding and protein interaction network of single-stranded DNA binding proteins (SSBs). SSBs are widely present in cells from lower prokaryotes to higher mammals and are important proteins for ssDNA protection. In-depth studies in recent years have revealed a wide range of interactions between SSBs and other proteins. Studies have shown that in addition to playing the role of ssDNA protector, SSBs are also important members of biochemical pathways such as DNA replication and recombination. In this study, a single-stranded DNA binding protein SSF encoded byE. coliF plasmid with highly conserved N-terminal region was demonstrated to have ssDNA binding ability similar toE. coliSSB through gel migration experiments. At the same time, the dsDNA binding ability of SSF was also demonstrated, and the dissociation constant of this interaction (in the range of microliters) was determined by Micro-scale Thermophoresis (MST). Through the above experiments, a previously unreported SSB with dsDNA binding ability was revealed, and the region interacting with dsDNA was determined to be the C-terminal unstructured region. This study lays a foundation for further understanding of the mechanism of bacterial conjugation conducted by F plasmid, as well as the potential dsDNA binding ability and biological significance of other SSBs.
The individual determinants of morning dream recall
Authors: Elce Valentina , Bergamo Damiana , Bontempi Giorgia , Pedreschi Bianca , Bellesi Michele , Handjaras Giacomo , Bernardi Giulio
Published: May 2024

Evidence suggests that (almost) everyone dreams during their sleep and may actually do so for a large part of the night. Yet, dream recall shows large interindividual variability. Understanding the factors that influence dream recall is crucial for advancing our knowledge regarding dreams' origin, significance, and functions. Here, we tackled this issue by prospectively collecting dream reports along with demographic information and psychometric, cognitive, actigraphic, and electroencephalographic measures in 204 healthy adults (18-70 y, 113 females). We found that attitude towards dreaming, proneness to mind wandering, and sleep patterns are associated with the probability of reporting a dream upon morning awakening. The likelihood of recalling dream content was predicted by age and vulnerability to interference. Moreover, dream recall appeared to be influenced by night-by-night changes in sleep patterns and showed seasonal fluctuations. Our results provide an account for previous observations regarding inter- and intra-individual variability in morning dream recall.
Unveiling the Evolution of CRISPR Spacer Number: A Phylogenetic Analysis of its Correlation with Repeat Characteristics
Authors: Liu Jia , Huang Rui , Niu Deng-Ke
Published: May 2024

CRISPR-Cas systems in prokaryotes utilize spacers, segments of DNA acquired from invading phages, to guide immune defense mechanisms. This study investigates the evolution of CRISPR repertoire size by examining its relationships with repeat length, terminal repeat polymorphism, and structural stability in 1,958 bacterial genomes, identifying 5,465 CRISPR arrays. Using CRISPRCasFinder for annotation and RNAfold for predicting RNA secondary structures, we found significant variation in array characteristics. Long-repeat arrays (≥38 bp) showed a significant positive correlation between terminal repeat polymorphism and CRISPR spacer number, a correlation absent in short-repeat arrays (<38 bp), suggesting longer repeats facilitate recombination and spacer loss. Additionally, a negative correlation between repeat length and spacer number across all arrays indicates that longer repeats may accelerate spacer loss. Furthermore, our results show that immune demand significantly influences the evolution of spacer number. Larger CRISPR repertoires correlate with conserved repeat sequences and stable secondary structures, vital for functional arrays under continuous selective pressure. Comparing functional and obsolete CRISPR arrays (orphan arrays in genomes lacking Cas genes) revealed that obsolete arrays have fewer spacers and lower repeat consistency, indicating a degenerative state. By elucidating the factors that shape CRISPR memory size evolution, this research offers strategies to enhance bacterial defenses, mitigate resistance, and improve applications in gene editing and therapeutics.
Representation of grasping type and force in the primate motor cortex
Authors: Moreno Adriana , de Lafuente Victor , Merchant Hugo
Published: May 2024

The primary motor cortex (M1) is strongly engaged by movement planning and movement execution. However, the role of M1 activity in voluntary grasping is still not completely understood. Here we analyze recordings of M1 neurons during the execution of a delayed reach-to-grasp task, where monkeys had to actively grasp an object with either a side or a precision grip, and then pull it with a low or high amount of force. Single cell and neural populations analyses showed that grip type was robustly and specifically encoded by a large population of neurons, while force level was weakly encoded within mixed-selective neurons that also provided grip type information. Notably, the grip type was stably decoded from motor cortical populations during the preparation and execution epochs of the task. Our results are consistent with the idea that planning and performing specific grasping movements are high-level skills that strongly engage M1 neurons, while the execution of grasping-pulling force might be prominently encoded at lower stages of the motor system.

Significance statement

Grasping behavior requires precise motor coordination exerted by multiple brain areas, including the primary motor cortex (M1), but the exact role of M1 in grasping preparation and execution remains elusive. Here, we analyzed the neural activity of M1 while two monkeys performed a delayed reach-to-grasp task. We found that two parameters of grasping: grip type and force level, were represented in the activity of single neurons and the neural population, although with important differences. While grip representation was stronger and more temporally stable, force encoding was weaker and short lived. Our results suggest that grip planning and execution is a high-level neural process that takes place independently of force control in M1.
Study of scalar nonstandard interaction at the Protvino to super-ORCA experiment
Authors: Singha Dinesh Kumar , Majhi Rudra , Panda Lipsarani , Ghosh Monojit , Mohanta Rukmani
Published: May 2024

In this paper we have studied the phenomenon of nonstandard interaction mediated by a scalar field (SNSI) in the context of P2SO experiment and compared its sensitivity with DUNE. In particular, we have studied the capability of these two experiments to put bounds on the diagonal SNSI parameters, i.e., ηee, ημμ, and ηττ and studied the impact of these parameters on the determination of neutrino mass ordering, octant of θ23 and CP violation (CPV). In our analysis we find that, the parameter Δm312 has a nontrivial role if one wants estimate the bounds on ημμ and

η

τ

τ

assuming SNSI does not exist in nature. Our results show that sensitivity of P2SO and DUNE to constraint ημμ and ηττ are similar whereas the sensitivity of DUNE is slightly better for ηee. We find that the mass ordering and CPV sensitivities are mostly affected by ηee compared to ημμ and ηττ if one assumes SNSI exists in nature. On the other hand, octant sensitivity is mostly affected by ημμ and ηττ. These sensitivities can be either higher or lower than the standard three flavor scenario depending on the relative sign of the SNSI parameters. Regarding the precision of atmospheric mixing parameters, we find that the precision of θ23 deteriorates significantly in the presence of ημμ and ηττ.

Published by the American Physical Society
2024
Training toward significance with the decorrelated event classifier transformer neural network
Authors: Kim Jaebak
Published: May 2024

Experimental particle physics uses machine learning for many tasks, where one application is to classify signal and background events. This classification can be used to bin an analysis region to enhance the expected significance for a mass resonance search. In natural language processing, one of the leading neural network architectures is the transformer. In this work, an event classifier transformer is proposed to bin an analysis region, in which the network is trained with special techniques. The techniques developed here can enhance the significance and reduce the correlation between the network’s output and the reconstructed mass. It is found that this trained network can perform better than boosted decision trees and feed-forward networks.

Published by the American Physical Society
2024