bluuebunny/crossref_metadata_2025 huggingface dataset:
The ELEVATE Study
Authors: Quaid Melissa L.
Published: September 2023

OBJECTIVE

The ELEVATE study evaluated whether an educational workshop would improve the perceptions of shared decision-making of nurses in an organization as demonstrated by an increase in Index of Professional Nursing Governance (IPNG) score.

BACKGROUND

Available literature insufficiently links educational interventions to improvements in shared professional governance.

METHODS

Six hundred ninety-one participants' IPNG scores were analyzed before and after an educational workshop was administered to formal administrative leaders and registered nurse (RN) RN council leaders every 6 months during a 2-year research study.

RESULTS

Index of Professional Nursing Governance scores were higher for RNs participating in nursing councils than scores for those who did not. The organization's IPNG scores remained stable from 2019 to 2021. Secondary analysis may suggest that council members were more resilient during crisis.

CONCLUSIONS

Further investigation is needed researching the relationship between professional governance education and RNs' perception of shared decision making.
Learning From Our Global Community of Nurses
Authors: Lal M. Maureen
Published: September 2023

Nursing is a global profession, with nearly 27 million nurses working around the world. This month's Magnet Perspectives examines the mutual benefit of this diverse and growing global community, puts the spotlight on some of the innovative initiatives taking place overseas, and considers how we can learn from each other to achieve our ultimate goals of an engaged nursing workforce, evidence-based patient care, and superior outcomes.
Update on the Use of Molecular Subtyping in Breast Cancer
Authors: Lawton Thomas J.
Published: September 2023

The standard of care for invasive cancers of the breast has been and continues to be to evaluate them for breast prognostic markers: estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 by immunohistochemistry. Over 2 decades ago, a study was the first to report on the molecular subtypes of breast cancer. Four main subtypes were reported. Since then there have been some changes in the molecular subtype classification, but overall many studies have shown that this subtyping has clinical prognostic and predictive value. More recently, molecular assays have been developed and studies have shown similar clinical prognostic and predictive value. We reviewed the literature for studies evaluating the clinical significance of all 3 of these methods of evaluation and the follow-up findings of that review are presented below.
Retching Without Vomiting With Acute Abdominal Distension: A Clinical Cue
Authors: Nalwalla Zahabiya , Dirkhipa Tsering Yangchen , Jain Rishabh , Shah Ira , Bendre Pradnya
Published: September 2023

Gastric volvulus leading to acute gastric dilatation is a rare presentation of congenital diaphragmatic hernia. Urgent detorsion with gastropexy and closure of the diaphragmatic defect are essential to prevent further complications and recurrence. We present a rare case of an infant with acute gastric dilatation due to acute gastric volvulus secondary to congenital diaphragmatic hernia.
Successful Treatment of Recurrent Pyloric Stenosis Using Balloon Dilation
Authors: Pirkle Jesseca R. A. , Deutsch David
Published: September 2023

Infantile hypertrophic pyloric stenosis is a common surgical disease in infants, with an incidence of 2 to 5 cases per 1000 live births. It often presents with nonbilious projectile vomiting after feeding and a mid-epigastric mass in infants between the third and eighth weeks of life. Ramstedt pyloromyotomy remains the gold standard of treatment. Postoperative emesis is common; however, further evaluation for incomplete pyloromyotomy and recurrent pyloric stenosis should be conducted with prolonged, or new-onset postoperative emesis. While repeat pyloromyotomy is the standard of care for infants presenting with incomplete pyloric stenosis, treatment for the rare development of recurrent pyloric stenosis is not clearly outlined. Here, we report a successful balloon dilation procedure in an 8-week-old female with recurrent pyloric stenosis three and a half weeks after the initial laparoscopic pyloromyotomy.
HLA Alleles in a Behçet Disease Multiethnic Population With and Without Ophthalmic Manifestations
Authors: de Andrade Francisco Assis , Porto Luís Cristóvão , Gomes Ochtrop Manuella Lima , Bacchiega Ana Beatriz Santos , de Almeida Neves Ricardo , Morette Leonardo , Santos Gilson , de Souza Alexandre Wagner Silva , Matos Kimble , Abramino Levy Roger
Published: September 2023

Objective

The aim of this study was to analyze HLA alleles in patients with Behçet disease (BD) and their correlation with ophthalmic manifestations (OMs) in a multiethnic Brazilian population.

Methods

This case-control study compared 72 BD patients with or without OM who underwent a thorough ophthalmologic evaluation, including best-corrected visual acuity, bino-ophthalmoscopy, and HLA analysis, with 144 matched healthy controls. Fluorescein angiography was also performed in the patients with BD and OM. HLA class I (A, B, and C) and II (DRB1, DQB1, and DQA1) typing were performed using PCR-SSO.

Results

Of 72 patients with BD, 42 (58%) had OM. The HLA-B*51 and -A*26 alleles were more frequent in patients with BD than in controls (23.6% vs 14.6% and 12.5% vs 4.3%, respectively), but could not differentiate OM risk. The HLA alleles of BD patients that differentiated those with and without OM were HLA-B*15 (40.5% vs 20.7%; odds ratio [OR], 2.59; p = 0.0059), HLA-C*02 (33.3% vs 13.4%; OR, 3.20; p = 0.0024), and HLA-DQB1*03 (64.3% vs 45.7%, p = 0.017), whereas HLA-A*03 (0.0% vs 13.3%, p = 0.006) and HLA-DRB1*15 (4.8% vs 19.5%; OR, 0.21; p = 0.0121) were protective against OM.

Conclusions

In this study of a Brazilian multiethnic BD population, alleles were similar between groups of BD patients with and without OM. We described HLA-B*15, -C*02, and -DQB1*03 as risk factors and -A*03 and -DRB1*15 as protective factors for OM in BD, which could function as biomarkers for predicting disease phenotypes.
Emergency Department and Inpatient Utilization Reductions and Cost Savings Associated with Trauma Center Mental Health Intervention
Authors: Prater Laura , Bulger Eileen , Maier Ronald V. , Goldstein Evan , Thomas Peter , Russo Joan , Wang Jin , Engstrom Allison , Abu Khadija , Whiteside Lauren , Knutzen Tanya , Iles-Shih Matt , Heagerty Patrick , Zatzick Doug
Published: September 2023

Objective:

The American College of Surgeons Committee on Trauma (ACS/COT) now requires that trauma centers have in place protocols to identify and refer patients at high risk for the psychological sequelae of traumatic injury. No investigations have documented reductions in utilization and associated potential cost savings associated with trauma center mental health interventions.

Summary Background Data:

The investigation was a randomized clinical trial analysis that incorporated novel 5-year emergency department/inpatient health service utilization follow-up data.

Methods:

Patients were randomized to a mental health intervention, targeting the psychological sequalae of traumatic injury (n= 85) versus enhanced usual care control (n= 86) conditions. The intervention included case management that coordinated trauma center-to-community care linkages, psychotropic medication consultation, and psychotherapy elements. Mixed model regression was used to assess intervention and control group utilization differences over time. An economic analysis was also conducted.

Results:

Over the course of the 5 years intervention patients demonstrated significant reductions in emergency department/inpatient utilization when compared to control patients (F [19,3210] =2.23, P =0.009]. Intervention utilization reductions were greatest at the 3-6 month (intervention 15.5% versus control 26.7%, Relative Risk [RR]=0.58, 95% Confidence Interval [95% CI] 0.34, 1.00) and 12-15 month (intervention 16.5% versus control 30.6%, RR=0.54, 95% CI 0.32, 0.91) post-injury time points. The economic analysis suggested potential intervention cost savings.

Conclusions:

Mental health intervention is associated with significant reductions in emergency department and inpatient utilization as well as potential cost savings. These findings could be productively integrated into future ACS/COT policy discussions.
Short Postoperative Intravenous Versus Oral Antibacterial Therapy in Complicated Acute Appendicitis – A Pilot Non-Inferiority Randomized Trial
Authors: Lipping Edgar , Saar Sten , Reinsoo Arvo , Bahhir Artjom , Kirsimägi Ülle , Lepner Urmas , Talving Peep
Published: September 2023

Objective:

The purpose of this study is to investigate noninferiority of postoperative oral administration of antibiotics in complicated appendicitis.

Background:

Recent investigations have used exclusively intravenous administration of antibiotics when comparing outcomes of postoperative antibacterial therapy in complicated appendicitis. We hypothesized that oral antibacterial treatment results in noninferior outcomes in terms of postoperative infectious complications as intravenous treatment.

Methods:

In this pilot, open-label, prospective randomized trial, all consecutive adult patients with complicated appendicitis including gangrenous appendicitis, perforated appendicitis, and appendicitis with periappendicular abscess between November 2020 and January 2023 were randomly allocated to 24-hour intravenous administration of antibiotics versus 24-hour oral administration of antibiotics after appendectomy. Primary outcomes included 30-day postoperative complications per Comprehensive Complication Index (CCI). Secondary outcome was hospital length of stay (HLOS). Follow-up analysis at 30 days was conducted per intention to treat and per protocol. The study was registered at ClinicalTrials.gov (NCT04947748).

Results:

A total of 104 patients were enrolled with 51 and 53 cases allocated to the 24-hour intravenous and the 24-hour oral treatment group, respectively. Demographic profile and disease severity score for acute appendicitis (DSS) were similar between the study groups. There were no significant differences between the study groups in terms of 30-day postoperative complications. Median CCI did not differ between the study groups. HLOS was similar in both groups.

Conclusions:

In the current pilot randomized controlled trial, the 24-hour oral antibiotic administration resulted in noninferior outcomes when compared to 24-hour intravenous administration of antibiotics after laparoscopic appendectomy in complicated appendicitis.
Neuroleptic Malignant Syndrome in Patients With Dementia: Experiences of A Single Memory Clinic
Authors: Isik Ahmet Turan , Kaya Derya , Ontan Mehmet Selman , Mutlay Feyza , Bulut Esra Ates , Dost Fatma Sena , Erken Neziha , Aydin Ali Ekrem
Published: September 2023

Objectives

Neuroleptic malignant syndrome (NMS) is a life-threatening condition that occurs as an adverse reaction to antipsychotic and antiemetic agents or sudden withdrawal of dopaminergic medications. Given the metabolic and functional reserves and the comorbidities in older adults, NMS may show an atypical course.

Methods

The medical records of patients with neurodegenerative diseases leading to dementia between 2013 and 2020 were reviewed for the diagnosis of NMS. Demographic and clinical characteristics of the patients were obtained from the records of laboratory parameters, management, and length of stay.

Results

Fifteen older adults (19 episodes) diagnosed with NMS were included. The median age was 76 years, and 5 were female. Ten of 15 NMS patients were atypical. Most of them had an infection accompanying NMS. Neuroleptic malignant syndrome was caused by antidopaminergic agents (5 antipsychotics, 1 metoclopramide) in 6 episodes and discontinuation of a dopaminergic agent, l-DOPA, in 12 episodes. In 1 patient, it was associated with simultaneous use of domperidone and amantadine withdrawal. Rigidity in NMS due to l-DOPA discontinuation was higher than in those due to antipsychotic use (P = 0.027). Two of our patients needed intensive care, and 1 died.

Conclusions

This study highlights the high frequency of atypical NMS and the importance of early recognition of this potentially fatal syndrome, which can accompany neurodegenerative diseases and infections in older adults.
Proposal of Allomuricauda gen. nov. and Allofranklinella gen. nov. as replacement names for the illegitimate prokaryotic generic names Muricauda and Franklinella, respectively
Authors: Deshmukh Umakant Bhoopati , Oren Aharon
Published: September 2023

The prokaryotic generic names

Muricauda

Bruns et al. 2001 and

Franklinella

Bernard et al. 2022 are illegitimate because they are later homonyms of the genus names

Muricauda

Small 1903 (synonym of Arisaema; Tracheophyta – Liliopsida – Araceae) and

Franklinella

Stewart and Hendrix 1945 (a Devonian ostracod genus) and

Franklinella

Lenz 1973 (a Devonian brachiopod genus), respectively (Principle 2 and Rule 51b(4) of the International Code of Nomenclature of Prokaryotes). We therefore propose the replacement generic names Allomuricauda and Allofranklinella, with type species Allomuricauda ruestringensis and Allofrankinella schreckenbergeri, respectively.
Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions
Authors: Wilkinson Jack , Heal Calvin , Antoniou George A. , Flemyng Ella , Alfirevic Zarko , Avenell Alison , Barbour Virginia , Brown Nicholas J L , Carlisle John , Clarke Mike , Dicker Patrick , Dumville Jo , Grey Andrew , Grohmann Steph , Gurrin Lyle C , Hayden Jill A , Heathers James , Hunter Kylie E , Lasserson Toby , Lam Emily , Lensen Sarah , Li Tianjing , Li Wentao , Loder Elizabeth , Lundh Andreas , Meyerowitz-Katz Gideon , Mol Ben W , O’Connell Neil E , Parker Lisa , Redman Barbara K. , Seidler Anna Lene , Sheldrick Kyle A , Sydenham Emma , Torgerson David J , van Wely Madelon , Wang Rui , Bero Lisa , Kirkham Jamie J
Published: September 2023

Introduction

Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INSPECT-SR project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare related interventions.

Methods and analysis

The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: 1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, 2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, 3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in 4) a consensus meeting to select checks to be included in a draft tool and to determine its format, 5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies, and will help patients by protecting them from the influence of false data on their healthcare.
Disease-driven domain generalization for neuroimaging-based assessment of Alzheimer’s disease
Authors: Lteif Diala , Sreerama Sandeep , Bargal Sarah A. , Plummer Bryan A. , Au Rhoda , Kolachalama Vijaya B.
Published: September 2023

Development of deep learning models to assess the degree of cognitive impairment on magnetic resonance imaging (MRI) scans has high translational significance. Performance of such models is often affected by potential variabilities stemming from independent protocols for data generation, imaging equipment, radiology artifacts, and demographic distributional shifts. Domain generalization (DG) frameworks have the potential to overcome these issues by learning signal from one or more source domains that can be transferable to unseen target domains. We developed an approach that leverages model interpretability as a means to improve generalizability of classification models across multiple cohorts. Using MRI scans and clinical diagnosis obtained from four independent cohorts (Alzheimer’s Disease Neuroimaging Initiative (ADNI,n= 1, 821), the Framingham Heart Study (FHS,n= 304), the Australian Imaging Biomarkers and Lifestyle Study of Ageing (AIBL,n= 661), and the National Alzheimer’s Coordinating Center (NACC,n= 4, 647)), we trained a deep neural network that used model-identified regions of disease relevance to inform model training. We trained a classifier to distinguish persons with normal cognition (NC) from those with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) by aligning class-wise attention with a unified visual saliency prior computed offline per class over all training data. Our proposed method competes with state-of-the-art methods with improved correlation with postmortem histology, thus grounding our findings with gold standard evidence and paving a way towards validating DG frameworks.
Microstructure-Informed Myelin Mapping (MIMM) from Gradient Echo MRI using Stochastic Matching Pursuit
Authors: Şişman Mert , Nguyen Thanh D. , Roberts Alexandra G. , Romano Dominick J. , Dimov Alexey V. , Kovanlikaya Ilhami , Spincemaille Pascal , Wang Yi
Published: September 2023

Quantification of the myelin content of the white matter is important for studying demyelination in neurodegenerative diseases such as Multiple Sclerosis (MS), particularly for longitudinal monitoring. A novel noninvasive MRI method, called Microstructure-Informed Myelin Mapping (MIMM), is developed to quantify the myelin volume fraction (MVF) by utilizing a multi gradient echo sequence (mGRE) and a detailed biophysical model of tissue microstructure. Myelin is modeled as anisotropic negative susceptibility source based on the Hollow Cylindrical Fiber Model (HCFM), and iron as isotropic positive susceptibility source in the extracellular region. Voxels with a range of biophysical parameters are simulated to create a dictionary of MR echo time magnitude signals and total susceptibility values. MRI signals measured using a mGRE sequence are then matched voxel-by-voxel to the created dictionary to obtain the spatial distributions of myelin and iron. Three different MIMM versions are presented to deal with the fiber orientation dependent susceptibility effects of the myelin sheaths: a basic variation, which assumes fiber orientation is an unknown to fit, two orientation informed variations, which assume the fiber orientation distribution is available either from a separate diffusion tensor imaging (DTI) acquisition or from a DTI atlas based fiber orientation map. While all showed a significant linear correlation with the reference method based on T2-relaxometry (p < 0.0001), DTI orientation informed and atlas orientation informed variations reduced overestimation at white matter tracts compared to the basic variation. Finally, the implications and usefulness of attaining an additional iron susceptibility distribution map are discussed.

Highlights

novel stochastic matching pursuit algorithm called microstructure-informed myelin mapping (MIMM) is developed to quantify Myelin Volume Fraction (MVF) using Magnetic Resonance Imaging (MRI) and microstructural modeling.

utilizes a detailed biophysical model to capture the susceptibility effects on both magnitude and phase to quantify myelin and iron.

matter fiber orientation effects are considered for the improved MVF quantification in the major fiber tracts.

acquired myelin and iron maps may be utilized to monitor longitudinal disease progress.
WITHDRAWN: Light affects the prefrontal cortex via intrinsically photosensitive retinal ganglion cells
Authors: Lazzerini-Ospri Lorenzo , Zhan Jesse J. , Thomsen Michael B. , Wang Hui , Messanvi Fany , du Hoffmann Johann , Cravedi Kevin , Komal Ruchi , Chudasama Yogita , Zhao Haiqing , Hattar Samer
Published: September 2023

Withdrawal Statement

This manuscript has been withdrawn by bioRxiv following a formal request by the NIH Intramural Research Integrity Office owing to lack of author consent.
Micrometer-thick, porous, nanocomposite coating for electrochemical sensors with exceptional antifouling and electroconducting properties
Authors: Lee Jeong-Chan , Kim Su Yeong , Song Jayeon , Jang Hyowon , Kim Hanul , Choi Siyoung Q. , Kim Sunjoo , Jolly Pawan , Kang Taejoon , Park Steve , Ingber Donald E.
Published: September 2023

Development of coating technologies for electrochemical sensors that consistently exhibit antifouling activities when exposed to diverse and complex biological environments over extended time is vital for development more effective medical devices and diagnostics. Here, we describe a micrometer-thick, porous nanocomposite coating with both exceptional antifouling and electroconducting properties that greatly enhance the sensitivity of electrochemical sensors. Nozzle-assisted printing of oil-in-water emulsion is used to create a 1 micrometer thick coating composed of cross-linked albumin with interconnected pores, which also contains electroconducting gold nanowires. Using this approach, the antifouling conductive coating can be deposited only on the surface of the working electrode, and not on the reference and counter electrodes, which greatly facilitates the fabrication and functionality of multiplexed electrochemical sensors. The layer effectively resists biofouling and maintains rapid electron transfer kinetics for over one month when exposed directly to complex biological fluids, including serum and nasopharyngeal secretions. Compared to previously described thinner (nanometer thick) antifouling electroconductive coating made with drop casting or a spin coating of the same thickness, the nozzle-printed sensors coated with this thick porous nanocomposite exhibited sensitivities that were enhanced by 3.75- to 17-fold when three different target biomolecules were tested. As a result, emulsion-coated, multiplexed electrochemical sensors coated were able to carry out simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid, antigen, and host antibody in clinical specimens with high sensitivity and specificity. This thick porous emulsion coating technology may provide a way to address hurdles currently restricting the application of electrochemical sensors for point-of-care (POC) diagnostic applications, as well as their use in implantable devices and other healthcare monitoring systems.
Label-free 3-D molecular imaging of living tissues using Raman Spectral Projection Tomography
Authors: Stepula Elzbieta , Walther Anders R. , Mehrotra Dev , Jensen Magnus , Yuan Mu H. , Pedersen Simon V. , Gentleman Eileen , Albro Michael B. , Hedegaard Martin A. B. , Bergholt Mads S.
Published: September 2023

The ability to image tissues in three-dimensions (3-D) with label-free molecular contrast at mesoscale would be a valuable capability in biology and biomedicine. Here, we introduce Raman spectral projection tomography (RSPT) for volumetric molecular imaging with sub-millimeter spatial resolution. We have developed a RSPT imaging instrument capable of providing 3-D molecular contrast in transparent and semi-transparent samples. A computational pipeline for multivariate reconstruction was established to extract label-free spatial molecular information from Raman projection data. We demonstrate imaging and visualization of phantoms of various complex shapes with label-free molecular contrast. Finally, we apply RSPT as a novel tool for imaging of molecular gradients and extracellular matrix heterogeneities in fixed and live tissue-engineered constructs and explanted native tissues. RSPT imaging opens new possibilities for label-free molecular monitoring of tissues.
Tuning of liver circadian transcriptome rhythms by thyroid hormone state in male mice
Authors: de Assis Leonardo Vinícius Monteiro , Harder Lisbeth , Lacerda José Thalles , Parsons Rex , Kaehler Meike , Cascorbi Ingolf , Nagel Inga , Rawashdeh Oliver , Mittag Jens , Oster Henrik
Published: September 2023

Thyroid hormones (THs) are important regulators of systemic energy metabolism. In the liver, they stimulate lipid and cholesterol turnover and increase systemic energy bioavailability. It is still unknown how the TH state interacts with the circadian clock, another important regulator of energy metabolism. We addressed this question using a mouse model of hypothyroidism and performed circadian analyses. Low TH levels decreased locomotor activity, food intake, and body temperature mostly in the active phase. Concurrently, liver transcriptome profiling showed only subtle effects compared to elevated TH conditions. Comparative circadian transcriptome profiling revealed alterations in mesor, amplitude, and phase of transcript levels in the livers of low-TH mice. Genes associated with cholesterol uptake, biosynthesis, and bile acid secretion showed reduced mesor. Increased and decreased cholesterol levels in the serum and liver were identified, respectively. Combining data from low- and high-TH conditions allowed the identification of 516 genes with mesor changes as molecular markers of the liver TH state. These genes participate in many known TH-associated processes. We further explored these genes and created a unique expression panel that can assess liver TH state in a time-of-day dependent manner. Our findings suggest that the liver has a low TH state under physiological conditions. Circadian profiling reveals genes as potential markers of liver TH state in one-time point studies.
Improved CAR-T cell activity associated with increased mitochondrial function primed by galactose
Authors: Gross Golda , Alkadieri Suha , Meir Amilia , Itzhaki Orit , Aharony-Tevet Yarden , Yosef Shahar Ben , Zenab Angi , Shbiro Liat , Toren Amos , Yardeni Tal , Jacoby Elad
Published: September 2023

CD19 CAR-T cells have led to durable remissions in patients with refractory B-cell malignancies; nevertheless, most patients eventually relapse in the long term. Many interventions aimed at improving current products have been reported, with a subset of them focusing on a direct or indirect link to the metabolic state of the CAR-T cells. We assessed clinical products from an ongoing clinical trial utilizing CD19-28z CAR-T cells from patients with acute lymphoblastic leukemia. CAR-T clinical products leading to a complete response had significantly higher mitochondrial function (by oxygen consumption rate) irrespective of mitochondrial content. Next, we replaced the carbon source of the media from glucose to galactose to impact cellular metabolism. Galactose-containing media increased mitochondrial activity in CAR-T cells, and improvedin vitroefficacy, without any consistent phenotypic change in memory profile. Finally, CAR-T cells produced in galactose-based glucose-free media resulted in increased mitochondrial activity. Using anin vivomodel of Nalm6 injected mice, galactose-primed CAR-T cells significantly improved leukemia-free survival compared to standard glucose-cultured CAR-T cells. Our results prove the significance of mitochondrial metabolism on CAR-T cell efficacy and suggest a translational pathway to improve clinical products.
Application of the Sepsis-3 criteria to describe sepsis epidemiology in the Amsterdam UMCdb intensive care dataset
Authors: Williams Christopher YK , Edinburgh Tom , Elbers Paul WG , Thoral Patrick J , Ercole Ari
Published: September 2023

Introduction

Sepsis is a major cause of morbidity and mortality worldwide. In the updated, 2016 Sepsis-3 criteria, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, where organ dysfunction can be represented by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more. We sought to apply the Sepsis-3 criteria the characterise the septic cohort in the Amsterdam University Medical Centres database (Amsterdam UMCdb).

Methods

We examined adult intensive care unit (ICU) admissions in the Amsterdam UMCdb, which contains de-identified data for patients admitted to a mixed surgical-medical ICU at a tertiary academic medical centre in the Netherlands. We operationalised the Sepsis-3 criteria, defining organ dysfunction as an increase in the SOFA score of 2 points or more, while infection was defined as a new course of antibiotics or an escalation in antibiotic therapy, with at least one antibiotic given intravenously. Patients with sepsis were determined to be in septic shock if they additionally required the use of vasopressors and had a lactate level >2 mmol/L.

Results

We identified 18,221 ICU admissions from 16,408 patients in our cohort. There were 6,371 unique sepsis episodes, of which 30.1% met the criteria for septic shock. A total of 4,958/6,371 sepsis (77.8%) episodes occurred on ICU admission. Forty-eight percent of emergency medical admissions and 37.0% of emergency surgical admissions were for sepsis. Overall, there was a 12.5% ICU mortality rate; patients with septic shock had a higher ICU mortality rate (38.5%) than those without shock (11.3%).

Conclusions

We successfully operationalised the Sepsis-3 criteria to the Amsterdam UMCdb, allowing the characterization and comparison of sepsis epidemiology across different centres.
Combination of QTL and GWAS to uncover the role of phosphodiesterases in ischemic heart disease
Authors: Xiao Jun , Gao Ziting , Wei Hongye , Wei Yajing , Qiu Ziyi , Huang Wuqing
Published: September 2023

Background

Phosphodiesterases (PDEs) are regarded as important therapeutic targets for multiple diseases, and the cardiovascular benefits of several PDE inhibitors have received extensive interests.

Objectives

To explore the relationship between genetically-predicted PDEs and ischemia heart disease via drug target Mendelian Randomization (MR) approach.

Methods

The expression of genes encoding PDEs was used to proxy the level of PDEs, and available quantitative trait loci of gene expression and DNA methylation (eQTLs and mQTLs) for each target gene were identified as the genetic instruments. Coronary heart disease (CHD) and myocardial infarction (MI) were the outcomes. Summary-data-based MR method was used to generate the estimates and two-step MR analysis was applied to investigate the mediation of metabolic traits.

Results

MR analyses identified two types of PDEs, PDE5 and PDE8, genetically-predicted expression in blood of the encoded genes was significantly associated with the risk of CHD (ORPDE5A=1.22,95% CI=1.06-1.40; ORPDE8A=1.26,95% CI=1.07-1.49) and MI (ORPDE5A=1.27,95% CI=1.09-1.48; ORPDE8A=1.24,95% CI=1.04-1.48). Especially, the highest expression of PDE5A was observed in artery aorta, which was also positively related to CHD (OR=1.17,95% CI=1.05-1.32) and MI (OR=1.15,95% CI=1.02-1.30). Besides, the methylation level of 12 CpG sites showed a relation with CHD or MI via affecting PDE5A expression. The observed association between PDE5A expression and outcomes were partly mediated by blood pressure and LDL cholesterol, and the association with MI were mostly mediated by CHD (Proportion-mediated: 78.84%).

Conclusions

This study provided genetic evidence about the protective role of PDE5 inhibition against ischemic heart disease, especially in preventing patients with CHD from developing MI.
CAMPER: curated annotations for profiling microbial polyphenol metabolic potential
Authors: McGivern Bridget B , Woyda Reed , Flynn Rory M , Wrighton Kelly C
Published: September 2023

Summary: Polyphenols are diverse and abundant carbon sources across ecosystems- having important roles in host-associated and terrestrial systems alike. However, the microbial genes encoding polyphenol metabolic enzymes are poorly represented in commonly used annotation databases, limiting widespread surveying of this metabolism. Here we present CAMPER, a tool that combines custom annotation searches with database-derived searches to both annotate and summarize polyphenol metabolism genes for a wide audience. With CAMPER, users will identify potential polyphenol-active genes and genomes to more broadly understand microbial carbon cycling in their datasets. Availability and Implementation: CAMPER is implemented in Python and is published under the GNU General Public License Version 3. It is available as both a standalone tool and as a database in DRAM v.1.5+. The source code and full documentation is available on GitHub at https://github.com/WrightonLabCSU/CAMPER.
Flamingo participates in multiple models of cell competition
Authors: Bosch Pablo Sanchez , Cho Bomsoo , Axelrod Jeffrey D.
Published: September 2023

The growth and survival of cells with different fitness, such as those with a proliferative advantage or a deleterious mutation, is controlled through cell competition. During development, cell competition enables healthy cells to eliminate less fit cells that could jeopardize tissue integrity, and facilitates the elimination of pre-malignant cells by healthy cells as a surveillance mechanism to prevent oncogenesis. Malignant cells also benefit from cell competition to promote their expansion. Despite its ubiquitous presence, the mechanisms governing cell competition, particularly those common to developmental competition and tumorigenesis, are poorly understood. Here, we show that inDrosophila, the planar cell polarity (PCP) protein Flamingo (Fmi) is required by winners to maintain their status during cell competition in malignant tumors to overtake healthy tissue, in early pre-malignant cells when they overproliferate among wildtype cells, in healthy cells when they later eliminate pre-malignant cells, and by supercompetitors as they compete to occupy excessive territory within wildtype tissues. “Would-be” winners that lack Fmi are unable to over-proliferate, and instead become losers. We demonstrate that the role of Fmi in cell competition is independent of PCP, and that it uses a distinct mechanism that may more closely resemble one used in other less well-defined functions of Fmi.
Sex differences in dispersal predict sex differences in helping across cooperative birds and mammals
Authors: Fenner Patrick , Currie Thomas E. , Young Andrew J.
Published: September 2023

Sex differences in cooperation are widespread, but their evolution remains poorly understood. Here we use phylogenetic comparative methods to test the Dispersal hypothesis for the evolution of sex differences in contributions to cooperative care across the cooperatively breeding birds and mammals. The Dispersal hypothesis predicts that, where non-breeding individuals of both sexes help to rear offspring within their natal group, the more dispersive sex will contribute less (either because leaving the natal group earlier reduces the downstream direct benefit from cooperation or because dispersal activities trade-off against cooperation). Our analyses reveal (i) support for the Dispersal hypothesis (sex biases in dispersal predict sex biases in natal cooperation across taxa), and (ii) that this pattern cannot be readily attributed to alternative hypothesized drivers of sex differences in cooperation (kin selection, heterogamety, paternity uncertainty, patterns of parental care or differences between birds and mammals). Our findings help to clarify the evolutionary drivers of sex differences in cooperation and highlight the need for single-species studies to now tease apart whether sex differences in dispersal predict sex differences in natal cooperation because dispersal impacts the direct benefits of natal cooperation (as is often proposed) or because activities that promote dispersal trade-off against natal cooperation.
The role of phages in proglacial stream biofilm communities characterized by microdiversity
Authors: Peter Hannes , Michoud Gregoire , Bhanu Busi Susheel , Battin Tom J.
Published: September 2023

Viruses modulate the diversity and activity of microbial communities. However, little is known about their role for the structure of stream biofilms communities. Here, we present insights into the diversity and composition of viral communities in various streams draining three proglacial floodplains in Switzerland. Proglacial streams are characterized by extreme environmental conditions, including near-freezing temperatures and ultra-oligotrophy. These conditions select for few but well-adapted bacterial clades, which dominate biofilm communities and occupy niches via microdiversification. We used metagenomic sequencing to reveal a remarkably diverse biofilm virome in these streams. Across the different floodplains and streams, viral community composition was tightly coupled to that of the bacterial hosts, which was underscored by generally high host specificity. Combining predictions of phage-host interactions with auxiliary metabolic genes (AMGs), we identify specific AMGs shared by phages infecting microdiverse clade members. Our work provides a step towards a better understanding of the complex interactions among bacteria and phages in stream biofilm communities in general and streams influenced by glacier meltwaters and characterized by microdiversity in particular.
Visual feature tuning properties of short-latency stimulus-driven ocular position drift responses during gaze fixation
Authors: Khademi Fatemeh , Zhang Tong , Baumann Matthias P. , Malevich Tatiana , Yu Yue , Hafed Ziad M.
Published: September 2023

Ocular position drifts during gaze fixation are generally considered to be random walks. However, we recently identified a short-latency ocular position drift response, of approximately 1 min arc amplitude, that is triggered within <100 ms by visual onsets. This systematic eye movement response is feature-tuned and seems to be coordinated with a simultaneous resetting of the saccadic system by visual stimuli. However, much remains to be learned about the drift response, especially for designing better-informed neurophysiological experiments unraveling its mechanistic substrates. Here we systematically tested multiple new feature tuning properties of drift responses. Using highly precise eye tracking in three male rhesus macaque monkeys, we found that drift responses still occur for tiny foveal visual stimuli. Moreover, the responses exhibit size tuning, scaling their amplitude as a function of stimulus size, and they also possess a monotonically increasing contrast sensitivity curve. Importantly, short-latency drift responses still occur for small peripheral visual targets, which additionally introduce spatially-directed modulations in drift trajectories towards the appearing peripheral stimuli. Drift responses also remain predominantly upward even for stimuli exclusively located in the lower visual field, and even when starting gaze position is upward. When we checked the timing of drift responses, we found that it was better synchronized to stimulus-induced saccadic inhibition timing than to stimulus onset. These results, along with a suppression of drift response amplitudes by peri-stimulus saccades, suggest that drift responses reflect the rapid impacts of short-latency and feature-tuned visual neural activity on final oculomotor control circuitry in the brain.

Significance

During gaze fixation, the eye drifts slowly in between microsaccades. While eye position drifts are generally considered to be random eye movements, we recently found that they are modulated with very short latencies by some stimulus onsets. Here we characterized the feature-tuning properties of such stimulus-driven drift responses. Our results demonstrate that drift eye movements are not random, and that visual stimuli can impact them in a manner similar to how such stimuli impact microsaccades.
Unveiling the Holliday junction conformational dynamics of upon binding with DNA architectural proteins IHF; A Single molecule FRET approach
Authors: Islam Farhana , Mishra Padmaja P.
Published: September 2023

Integration host factor (IHF) ofE. coliis a nucleoid-associated protein with diverse roles in DNA packaging, viral DNA integration, and recombination. IHF binds to duplex DNA containing a 13 bp consensus sequence with nanomolar affinity and induces a significant bend of approximately 160° upon binding. While the Wild type IHF (WtIHF) is involved in DNA bending, thereby facilitating the integration of foreign DNA into the host genome, its engineered version, Single chain IHF (ScIHF) was designed for specific genetic engineering and biotechnological applications. We investigated interaction of the two IHF variants with Holliday junctions (HJ), crucial intermediates in DNA repair and homologous recombination. Our finding demonstrate that both variant of IHF binds to HJs with high affinity in presence of the consensus sequence, indicating a structure-based recognition mechanism. HJs are dynamic structures that can adopt open or stacked conformation. The open conformation facilitates processes like branch migration and strand exchange. Through quantitative binding studies using microscale thermophoresis, we determined the binding of IHF to four-way DNA junctions that harboured two specific binding sequences H’ & H1. Circular dichroism (CD) experiments revealed the protein’s impact on the junction conformation. This was further confirmed by Single molecule Förster resonance energy transfer (smFRET) technique that was used to examine the binding of IHF to the junction and its effect on the dynamicity of junction conformation. We also probed the population distribution of junction conformations. Interestingly, our results revealed that binding of both WtIHF & ScIHF shifts the population towards the open conformation of the junction and stabilised it in that conformation. In summary, our findings demonstrate that IHF binds HJs with a strong affinity and has a stabilizing effect on maintaining the junction’s open conformation.
Observing femtosecond orbital dynamics in ultrafast Ge melting with time-resolved resonant X-ray scattering
Authors: Lee Heemin , Ahn Je Young , Chun Sae Hwan , Cho Do Hyung , Sung Daeho , Jung Chulho , Shin Jaeyong , Hwang Junha , Ha Sung Soo , Jang Hoyoung , Cho Byeong-Gwan , Kim Sunam , Park Jaeku , Nam Daewoong , Eom Intae , Shim Ji Hoon , Noh Do Young , Ihm Yungok , Song Changyong
Published: September 2023

Photoinduced nonequilibrium phase transitions have stimulated interest in the dynamic interactions between electrons and crystalline ions, which have long been overlooked within the Born–Oppenheimer approximation. Ultrafast melting before lattice thermalization prompted researchers to revisit this issue to understand ultrafast photoinduced weakening of the crystal bonding. However, the absence of direct evidence demonstrating the role of orbital dynamics in lattice disorder leaves it elusive. By performing time-resolved resonant X-ray scattering with an X-ray free-electron laser, we directly monitored the ultrafast dynamics of bonding orbitals of Ge to drive photoinduced melting. Increased photoexcitation of bonding electrons amplifies the orbital disturbance to expedite the lattice disorder approaching the sub-picosecond scale of the nonthermal regime. The lattice disorder time shows strong nonlinear dependence on the laser fluence with a crossover behavior from thermal-driven to nonthermal-dominant kinetics, which is also verified by ab initio and two-temperature molecular dynamics simulations. This study elucidates the impact of bonding orbitals on lattice stability with a unifying interpretation on photoinduced melting.
The role of urban green spaces in supporting active and healthy ageing: an exploration of behaviour–physical setting–gender correlations
Authors: Ye Xi , Ren Xuan , Shang Yuanzheng , Liu Jiayu , Feng Huangyu , Zhang Yun
Published: September 2023

Purpose

Urban green spaces support people to approach active, healthy ageing, especially in high-density cities where they compensate for limited private living spaces. This research paper aims to examine how urban green spaces support active, healthy ageing by exploring correlations between behaviour, physical setting and gender difference among older people in a highly populated urban context.

Design/methodology/approach

Urban parks in older neighbourhoods of Macau were selected for data collection. Photographic documentation was used to collect data, with 1,201 older people photographed identified as valid samples. Each was coded according to labels of behaviour, physical setting and gender. Chi-squared tests were conducted to assess correlations between behaviours and features of physical settings, and differences between genders in behaviours and physical settings. Logistic regression analysis was conducted to further examine associations between older people's behaviours and features of physical settings by gender.

Findings

The research reveals types and frequency of behaviours displayed, preferred environmental features for different behaviours and gender differences in behaviours and preferred environmental features. Design principles targeting active, healthy ageing should consider particular amenities and street furniture, the arrangement of trees and landscapes and the integration of open and secluded places.

Originality/value

Previous studies address older people's behaviour from the perspective of either environmental influence or gender difference, but there have been few studies on gendered behavioural differences among older people in urban green spaces. Analysing the behaviour–physical setting–gender relationship provides more evidence in the field of built environment studies.
Digital transformation of work: Swiss MSEs working from home behaviour during COVID-19 – pioneers leading the pack
Authors: Peter Marc K. , Wuersch Lucia , Wong Alfred , Neher Alain
Published: September 2023

Purpose

The purpose of this study is to better understand technology adoption and working from home (WFH) behaviour of micro and small enterprises (MSE) with 4 to 49 employees during the first (2020) and second (2021) COVID-19 lockdowns in Switzerland.

Design/methodology/approach

This study uses two data sets gathered using computer-assisted telephone interviewing surveys conducted with 503 managing directors of Swiss MSEs after the first and 506 MDs after the second COVID-19 lockdown period.

Findings

The study revealed that during the COVID-19 pandemic, WFH arrangements are related to the adoption of technology by Swiss industry groups. Furthermore, industry characteristics and technology adoption strategies are also associated with the long-term prospect of WFH. The overall result confirms the predominant role of technology pioneers.

Research limitations/implications

The study focuses on MSEs in Switzerland during a specific period. The data set includes mainly quantitative data. Future studies could investigate larger enterprises in international contexts, integrating employees’ viewpoints founded on long-term gathered qualitative data. The implications of this study include predictions about future WFH behaviour in Swiss MSEs.

Originality/value

To the best of the authors’ knowledge, this is the first study collecting data in Swiss MSEs after the two COVID-19 lockdowns in 2020 and 2021. As a result, this study offers a unique perspective on a specific business segment, which accounts for around 70% of global employment.