bluuebunny/crossref_metadata_2025 huggingface dataset:
A Qualitative Study of Midlevel Nurse Managers' Perspectives of Scholarly Inquiry
Authors: Lombardo Mary Jo , Vioral Anna , Ley Cathaleen , Alderfer Mary Ellen , Mackay Periwinkle , Kverno Karan , Milburn Rowena Leong , Hohl Dawn , Lindauer Cathleen , Gerstenhaber Melissa
Published: March 2023

OBJECTIVE

This study explored the key characteristics and needs of midlevel nurse managers (MLNMs) who support and engage clinical nurses (CNs) in scholarly inquiry.

BACKGROUND

Healthcare organizations expect CNs to participate in scholarly inquiry, incorporating evidence-based interventions to improve outcomes and safety. How the MLNM supports and engages CNs in scholarly inquiry remains unclear.

METHODS

Twelve semistructured interviews of MLNMs occurred at several facilities in the mid-Atlantic region utilizing the institutional review board–acknowledged protocol. Theme interpretation utilized inductive analysis.

RESULTS

Four recurrent themes emerged from the interviews related to the value of scholarly inquiry: 1) securing organizational resources to promote scholarly inquiry; 2) knowledge and experience in scholarly inquiry; 3) actions supporting scholarly inquiry; and 4) the value of scholarly inquiry within the organization.

CONCLUSIONS

Senior nursing leadership and healthcare organizations must recognize the value and provide the infrastructure to support scholarly inquiry. Infrastructure includes education, dedicated time, access to expertise, and resources.
The impact of running with and without a guide on short distance running performance for athletes with a vision impairment
Authors: Zenk Franziska , Willmott Ashley G. B. , Mann David L. , Allen Peter M.
Published: March 2023

Objective

This study aimed to investigate the difference of running with or without a guide on running performance (100 m, 200 m and 400 m) for athletes with a vision impairment (VI).

Design

Data including athletes’ and guides’ sex, age and race times were extracted from 11 elite competitions.

Results

Male athletes predominantly ran without a guide (100 m = 91.4%, 200 m = 88.1%, 400 m = 84.8%), whereas, female athletes mainly ran with a guide (100 m = 60.5%, 200 m = 80.0%, 400 m = 72.0%). No significant difference in 100 m race times was found between male athletes with or without a guide (p = 0.647). For the 200 m (p = 0.001) and 400 m (p = 0.030), race times were significantly slower for male athletes running with a guide (mean rank 200 m = 36.80, 400 m = 33.57) compared to without a guide (mean rank 200 m = 19.43, 400 m = 21.69). Conversely, 100 m (p = 0.015), 200 m (p = 0.025) and 400 m (p = 0.029) race times were significantly faster for female athletes with (mean rank 100 m = 18.25, 200 m = 13.71, 400 m = 11.00) compared to without a guide (mean rank 100 m = 27.74, 200 m = 22.67, 400 m = 21.69).

Conclusions

Running with a guide affects VI athletes’ race times. The influence of running with a guide, and the gender mix of VI athlete and guide, should be considered in any research with the aim of establishing a new classification system for VI athletes.
In the Cone of Concern: Preparing Stroke Survivors for Extreme Hurricanes
Authors: Issac Sony , Shultz James M. , Espinel Zelde , Alvarez Gemayaret , Shapiro Lauren T.
Published: March 2023

When disasters strike, individuals living with stroke-related disability experience unique challenges and hardships. Climate change is contributing to the increasing frequency and severity of extreme weather events, including major hurricanes. Cyclonic storms that threaten the health and safety of residents living in coastal and island communities may disproportionately impact stroke survivors. Stroke sequelae may impede individuals’ abilities to engage in timely preparedness and self-protective actions when such storms approach. As such, it is imperative that physiatrists and other health care professionals caring for patients living with stroke proactively assist them in identifying their needs and in developing tailored, comprehensive emergency preparedness plans. In this paper, we examine the special needs of and considerations for persons living with stroke sequelae in the times leading up to, during, and after a major hurricane. We also put forward recommendations, specific to the phases of a disaster, regarding how physiatrists can assist patients living with stroke, and their caregivers, to optimize preparedness in advance of a hurricane, and facilitate effective response during storm impact and in the aftermath.
Effects of Orthopedic Manual Therapy on Pain Sensitization in Patients with Chronic Musculoskeletal Pain: An Umbrella Review with Meta-Meta-Analysis
Authors: Martínez-Pozas Oliver , Sánchez-Romero Eleuterio A. , Beltran-Alacreu Héctor , Arribas-Romano Alberto , Cuenca-Martínez Ferran , Villafañe Jorge Hugo , Fernández-Carnero Josué
Published: March 2023

Objective

The aim of this umbrella review with meta-meta-analysis was to assess the effectiveness of orthopedic manual therapy in isolation on pain sensitization in patients with chronic musculoskeletal pain.

Design

A systematic search was performed in different databases including systematic reviews with or without meta-analysis. The outcome measures included were pressure pain threshold, temporal summation, and conditioned pain modulation. We statistically synthesized the results of the different reviews through a random-effect meta-analysis of all standardized mean differences and the corresponding 95% confidence interval reported by each study.

Results

For mechanical hyperalgesia, the meta-meta-analysis of three meta-analysis revealed a statistically significant small-moderate effect of orthopedic manual therapy, with no evidence of heterogeneity and moderate quality evidence. In terms of temporal summation, one meta-analysis revealed a statistically significant small effect of orthopedic manual therapy intervention, with moderate heterogeneity and low quality of evidence. Finally, one review without meta-analysis found that orthopedic manual therapy improved endogenous analgesia with low quality evidence.

Conclusion

Orthopedic manual therapy in isolation improved mechanical hyperalgesia with moderate quality evidence, as well as temporal summation and conditioned pain modulation with low quality evidence. However, its effects are limited only to immediate and short-term.
Psychoeducational Intervention for Reducing Heart Failure Patients’ Rehospitalizations and Promoting Their Quality of Life and Posttraumatic Growth at the 1-Year Follow-Up: A Randomized Clinical Trial
Authors: de Oliveira Filipa Waihrich , Nunes Brenda Pereira , Lobato Fernanda Lucchese , Schmidt Márcia Moura
Published: March 2023

Objective

This study’s aim was to verify whether a psychoeducational intervention, with a brief expressive posttraumatic growth (PTG) component, could reduce heart failure (HF) patients’ hospital readmissions and promote their quality of life (QoL) and PTG.

Methods

It adopted a parallel randomized clinical trial design, and its participants comprised HF patients from a hospital in Southern Brazil. All the participants completed the World Health Organization Quality of Life Assessment and Posttraumatic Growth Inventory questionnaires at the pre (T1: baseline) and post (T2) assessments of the intervention. Although patients in the control group (CG) underwent only regular outpatient consultations, those in the intervention group (IG) supplemented their regular consultations, with two additional individual visits to promote health and psychological education. At the 1-year follow-up, hospital readmissions were assessed.

Results

Of the 142 patients recruited at baseline (72 and 70 in the CG and IG, respectively), as 19 dropped out at follow-up, only 123 (63 and 60 in the CG and IG, respectively) were reassessed after approximately 378 days. They included 65% men aged 64 (11) years, 58% had low incomes, and 67% had less than high school education. The IG participants’ risk of readmission got reduced by 52% (p = .023), and they also showed significant improvements in their total QoL and positive psychological growth at the 6-month follow-up assessment.

Conclusions

The two-session psychoeducational intervention proved to be protective for Southern Brazilian HF patients in the IG, as it effectively reduced their hospital readmission rates by half compared with the CG, as well as improved their QoL and promoted their positive psychological growth.

Trial Registration

ClinicalTrials.gov identifier: NCT04870918.
Functional Somatic Disorders, Their Subtypes, and Their Association With Self-Rated Health in the German General Population
Authors: Sattel Heribert , Häuser Winfried , Schmalbach Bjarne , Brähler Elmar , Henningsen Peter , Hausteiner-Wiehle Constanze
Published: March 2023

Objective

The heterogeneous conceptualizations and classifications of persistent and troublesome physical symptoms impede their adequate clinical management. Functional somatic disorder (FSD) is a recently suggested interface concept that is etiologically neutral and allows for dysfunctional psychobehavioral characteristics as well as somatic comorbidity. However, its prevalence and impact are not yet known.

Methods

We analyzed 2379 participants (mean age = 48.3 years, 52.5% female) from a representative German community survey using operationalized FSD criteria. These criteria defined FSD types based on somatic symptom count, type, and severity assessed by the Bodily Distress Syndrome Checklist. In addition, the associations of those types with health concerns, comorbidity, psychological distress, and self-rated health were determined.

Results

There were four clearly demarcated groups with no relevant bothering symptoms, with one or with few bothering symptoms from one organ system, and with multiple bothering symptoms from at least two organ systems. Psychological distress, health concerns, and comorbidity steadily increased, and self-rated health decreased according to the number and severity of symptoms. Somatic symptom burden, health concerns, and comorbidity independently predicted self-rated health, with no interaction effect between the latter two.

Conclusions

Our data support an FSD concept with two severity grades according to persistent and troublesome symptoms in one versus more organ systems. The delimitation of subtypes with psychobehavioral characteristics and/or with somatic comorbidity seems useful, while still allowing the demarcation of a group of participants with high symptom burden but without those additional characteristics.
The Role and Advantages of Cardiac Magnetic Resonance in the Diagnosis of Myocardial Ischemia
Authors: Silva Thiago Quinaglia A.C. , Pezel Théo , Jerosch-Herold Michael , Coelho-Filho Otávio R.
Published: March 2023

Ischemic heart disease continues to be the leading cause of death and disability worldwide. For the diagnosis of ischemic heart disease, some form of cardiac stress test involving exercise or pharmacological stimulation continues to play an important role, despite advances within modalities like computer tomography for the noninvasive detection and characterization of epicardial coronary lesions. Among noninvasive stress imaging tests, cardiac magnetic resonance (CMR) combines several capabilities that are highly relevant for the diagnosis of ischemic heart disease: assessment of wall motion abnormalities, myocardial perfusion imaging, and depiction of replacement and interstitial fibrosis markers by late gadolinium enhancement techniques and T1 mapping. On top of these qualities, CMR is also well tolerated and safe in most clinical scenarios, including in the presence of cardiovascular implantable devices, while in the presence of renal disease, gadolinium-based contrast should only be used according to guidelines. CMR also offers outstanding viability assessment and prognostication of cardiovascular events. The last 2019 European Society of Cardiology guidelines for chronic coronary syndromes has positioned stress CMR as a class I noninvasive imaging technique for the diagnosis of coronary artery disease in symptomatic patients. In the present review, we present the current state-of-the-art assessment of myocardial ischemia by stress perfusion CMR, highlighting its advantages and current shortcomings. We discuss the safety, clinical, and cost-effectiveness aspects of gadolinium-based CMR-perfusion imaging for ischemic heart disease assessment.
Cardiac Magnetic Resonance Imaging T1 and T2 Mapping in Systemic Lupus Erythematosus in Relation to Antimalarial Treatment
Authors: Shalmon Tamar , Thavendiranathan Paaladinesh , Seidman Michael A. , Wald Rachel M. , Karur Gauri Rani , Harvey Paula J. , Akhtari Shadi , Osuntokun Tosin , Tselios Kostantinos , Gladman Dafna D. , Hanneman Kate
Published: March 2023

Purpose:

Patients with systemic lupus erythematosus (SLE) are at risk of cardiac disease including antimalarial-induced cardiomyopathy (AMIC). The purpose of this study is to evaluate cardiac magnetic resonance imaging parametric mapping findings in SLE patients with AMIC and investigate the relationship of T1/T2 mapping to antimalarial (AM) treatment duration.

Materials and Methods:

All patients with SLE who had undergone cardiac magnetic resonance imaging with T1/T2 mapping for evaluation of suspected cardiac disease between 2018 and 2021 were evaluated and compared with healthy controls. To facilitate comparison between scanners, T1/T2 values were converted to a z-score using scanner-specific local reference values. Patients were classified into 3 groups: AMIC, myocarditis, and other (no AMIC or myocarditis).

Results:

Forty-five SLE patients (47±17 y, 80% female; 8 [18%] with AMIC and 7 [16%] with myocarditis) and 30 healthy controls (39±15 y, 60% female) were included. Patients with AMIC had higher T1 and T2 compared with controls (z-score 1.1±1.3 vs. 0±0.6, P=0.01 and 1.7±1.1 vs. 0±1.0, P<0.01, respectively) and lower values compared with those with myocarditis (3.7±1.6, P<0.01 and 4.0±2.0, P<0.01, respectively). T1 correlated negatively with AM treatment duration in patients without AMIC or myocarditis (r=−0.36, P=0.048) and positively in patients with AMIC (r=0.92, P=0.001). AM treatment duration did not correlate significantly with T1 in patients with myocarditis or with T2 in any group.

Conclusions:

The relationship between T1 and AM treatment duration differed between groups. Native T1 decreases with longer treatment in patients without AMIC or myocarditis, possibility due to glycosphingolipid accumulation. In patients with AMIC, increasing T1 with longer treatment could reflect fibrosis.
Are Interstitial Lung Abnormalities a Prognostic Factor of Worse Outcome in COVID-19 Pneumonia?
Authors: Colombi Davide , Petrini Marcello , Morelli Nicola , Silva Mario , Milanese Gianluca , Sverzellati Nicola , Michieletti Emanuele
Published: March 2023

Purpose:

To assess the association between interstitial lung abnormalities (ILAs) and worse outcome in patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19)-related pneumonia.

Materials and Methods:

The study included patients older than 18 years, who were admitted at the emergency department between February 29 and April 30, 2020 with findings of COVID-19 pneumonia at chest computed tomography (CT), with positive reverse-transcription polymerase chain reaction nasal-pharyngeal swab for SARS-CoV-2, and with the availability of prepandemic chest CT. Prepandemic CTs were reviewed for the presence of ILAs, categorized as fibrotic in cases with associated architectural distortion, bronchiectasis, or honeycombing. Worse outcome was defined as intensive care unit (ICU) admission or death. Cox proportional hazards regression analysis was used to test the association between ICU admission/death and preexisting ILAs.

Results:

The study included 147 patients (median age 73 y old; 95% CIs: 71-76-y old; 29% females). On prepandemic CTs, ILA were identified in 33/147 (22%) of the patients, 63% of which were fibrotic ILAs. Fibrotic ILAs were associated with higher risk of ICU admission or death in patients with COVID-19 pneumonia (hazard ratios: 2.73, 95% CIs: 1.50-4.97, P=0.001).

Conclusions:

In patients affected by COVID-19 pneumonia, preexisting fibrotic ILAs were an independent predictor of worse prognosis, with a 2.7 times increased risk of ICU admission or death. Chest CT scans obtained before the diagnosis of COVID-19 pneumonia should be carefully reviewed for the presence and characterization of ILAs.
Molecular and Cellular Crosstalk between Bone and Brain: Accessing Bidirectional Neural and Musculoskeletal Signaling during Aging and Disease
Authors: Schurman Charles A. , Burton Jordan B. , Rose Jacob , Ellerby Lisa M. , Alliston Tamara , Schilling Birgit
Published: March 2023

Molecular omics technologies, including proteomics, have enabled the elucidation of key signaling pathways that mediate bidirectional communication between the brain and bone tissues. Here we provide a brief summary of the clinical and molecular evidence of the need to study the bone–brain axis of cross-tissue cellular communication. Clear clinical and molecular evidence suggests biological interactions and similarities between bone and brain cells. Here we review the current mass spectrometric techniques for studying brain and bone diseases with an emphasis on neurodegenerative diseases and osteoarthritis/osteoporosis, respectively. Further study of the bone–brain axis on a molecular level and evaluation of the role of proteins, neuropeptides, osteokines, and hormones in molecular pathways linked to bone and brain diseases is critically needed. The use of mass spectrometry and other omics technologies to analyze these cross-tissue signaling events and interactions will help us better understand disease progression and comorbidities and potentially identify new pathways and targets for therapeutic interventions. Proteomic measurements are particularly favorable for investigating the role of signaling and secreted and circulating analytes and identifying molecular and metabolic pathways implicated in age-related diseases.
Seasonal Variations and Common Places of Hip Fractures in Elderly Patients: Nine Year Consecutive Survey
Authors: Choi Kyung-A , Ha Yong-Chan , Lee Kyung-Hag
Published: March 2023

Background: Fall prevention is important for reducing hip fractures. The aim of this study was to determine the relationship between variables related to hip fractures according to sex and season.Methods: This study included patients admitted for fragility hip fractures between 2012 and 2021. Patients were interviewed by a junior resident before discharge. Data on sex, age, diagnosis, osteoporosis treatment, direction, voiding problems, ambulatory function, seasons, weather, time of day, place, location, floor condition, activity during fall, and perceived reason for fall were collected and analyzed.Results: A total of 1,118 patients were included (279 males and 839 females). In both sexes, indoor falls were prevalent throughout all seasons, but males showed a higher proportion of outdoor falls, especially in winter during cloudy or snowy weather. Rooms and walking were the most common locations and activities during falls. The poor ambulatory function was associated with a higher prevalence of indoor falls. Osteoporosis treatment rates were low and did not differ according to Koval stage. Winter was associated with higher osteoporosis non-treatment group. Urgency/incontinence in female patients caused a higher proportion of falls during the evening time.Conclusions: Strategies for indoor fall prevention and vigilant osteoporosis diagnosis and treatment are important for all seasons, especially for frail elderly patients. Outdoor fall prevention emphasized for male patients, and education around nighttime falls should be provided for female patients with voiding dysfunction.
Bone Mineral Density in Patients with Pediatric Inflammatory Bowel Disease Using Dual Energy X-Ray Absorptiometry
Authors: Isa Hasan M. , Ezzaldin Amira A. , Alabbasi Mohamed M. , ALaazmi Noora H. , Masood Abdulrahman S. , Alabbasi Hissa M.
Published: March 2023

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory immune-mediated condition that affects the gastrointestinal system and alters bone growth and bone mineral density (BMD). Here we aimed to study the prevalence and predictors of a low BMD in pediatric patients with IBD.Methods: This retrospective cross-sectional analytical study included pediatric patients with IBD in whom BMD was evaluated using dual energy X-ray absorptiometry of the total body and lumbar spine. Osteoporosis was defined as a BMD Z-score ≤-2, osteopenia as -2 to -1, and normal as >-1. Clinical and laboratory findings were compared between patients with and without osteoporosis.Results: Of the 48 patients, 30 (62.5%) were males, 35 (72.9%) had Crohn’s disease, and 13 (27.1%) had ulcerative colitis. The mean age at diagnosis was 9.9±2.8 years. The median age at the time of the BMD scans was 11.9 (interquartile range, 9.9–14.3) years. Total body BMD scans identified 13 (27.1%) and 16 (33.3%) patients with osteoporosis and osteopenia, respectively. Spinal BMD scans revealed that 17 (39.5%) and 14 (32.6%) patients had osteoporosis and osteopenia, respectively. A low body mass index (BMI) Z-score (p=0.038), ileocolonic disease location (p=0.008), and a low calcium level (p=0.008) were significant predictors of osteoporosis on the total body BMD scans. A low BMI Z-score (p=0.039), decreased hemoglobin level (p=0.018), low calcium level (p=0.033), and infliximab use (p=0.019) were significant predictors of osteoporosis on the spinal BMD scans.Conclusions: This study showed a high prevalence of low BMD among pediatric patients with IBD. A low BMI, ileocolonic disease location, low hemoglobin and calcium levels, and infliximab use were significantly associated with osteoporosis.
Association of rare variants inARSAwith Parkinson’s disease
Authors: Senkevich Konstantin , Beletskaia Mariia , Dworkind Aliza , Yu Eric , Ahmad Jamil , Ruskey Jennifer A. , Asayesh Farnaz , Spiegelman Dan , Fahn Stanley , Waters Cheryl , Monchi Oury , Dauvilliers Yves , Dupré Nicolas , Greenbaum Lior , Hassin-Baer Sharon , Nagornov Ilya , Tyurin Alexandr , Miliukhina Irina , Timofeeva Alla , Emelyanov Anton , Zakharova Ekaterina , Alcalay Roy N. , Pchelina Sofya , Gan-Or Ziv
Published: March 2023

Background

Several lysosomal genes are associated with Parkinson’s disease (PD), yet the association between PD andARSA, which encodes for the enzyme arylsulfatase A, remains controversial.

Objectives

To evaluate the association between rareARSAvariants and PD.

Methods

To study possible association of rare variants (minor allele frequency<0.01) inARSAwith PD, we performed burden analyses in six independent cohorts with a total of 5,801 PD patients and 20,475 controls, using optimized sequence Kernel association test (SKAT-O), followed by a meta-analysis.

Results

We found evidence for an association between functionalARSAvariants and PD in four independent cohorts (P≤0.05 in each) and in the meta-analysis (P=0.042). We also found an association between loss-of-function variants and PD in the UKBB cohort (P=0.005) and in the meta-analysis (P=0.049). However, despite replicating in four independent cohorts, these results should be interpreted with caution as no association survived correction for multiple comparisons. Additionally, we describe two families with potential co-segregation of theARSAvariant p.E384K and PD.

Conclusions

Rare functional and loss-of-functionARSAvariants may be associated with PD. Further replication in large case-control cohorts and in familial studies is required to confirm these associations.
Role of MicroRNA-22 (miR-22)/Specificity protein 1 (Sp1)/Cystathionine β-synthase (CBS) axis in regulating trophoblast invasion: an in vitro study
Authors: Arora Pallavi , Mochan Sankat , Gupta Sunil Kumar , Rani Neerja , Kshetrapal Pallavi , Dwivedi Sadanand , Bhatla Neerja , Dhingra Renu
Published: March 2023

Introduction

Placenta expresses many ubiquitous as well as specific miRNAs which regulate trophoblast cell differentiation, proliferation, apoptosis, invasion, migration, and angiogenesis. Aberrant miRNAs expression (miR-22) has been linked to pregnancy complications, such as preeclampsia. Specificity protein 1 (Sp1) was identified a direct target of miR-22 and an inverse linear correlation between expression of miR-22 and Sp1 mRNA in gastric tumour has been reported. Also, Sp1 has a critical and indispensable role in the regulation of cystathionine β-synthase (H2S synthesizing enzyme). Exogenous H2S could promote cell proliferation and invasion by upregulating the expression of MMP-2 and MMP-9 in human bladder cancer EJ cells. Worldwide studies reported significant role of MMP-2 and MMP-9 in the regulation of trophoblast invasion.

Aims and Objectives

To determine the role of MicroRNA-22 (miR-22)/Specificity protein 1 (Sp1)/Cystathionine β-synthase (CBS) axis in regulating trophoblast invasion in the first-trimester trophoblast cells.

Materials and methods

The human first trimester trophoblast cell line (HTR-8/SVneo Cell line) was procured from American Type Culture Collection. Gain/Loss of function studies were conducted on HTR-8/SVneo cells and the expression of miR-22 (pre miR-22 and miR-22-3p), Sp1, CBS, MMP-2 and MMP-9 was observed. Invasion capacity of the cells was assessed by transwell invasion assay. Data were analyzed by STATA 14 and Graph Pad Prism 8.

Results

Significantly down regulated regulated mRNA and protein expression of Sp1, CBS and and MMPs 2, 9 was observed when the cells were transfected with miR-22-3p mimic in comparison to miR-22-3p inhibitor transfected cells. Expression of CBS and MMPs 2, 9 was found to be significantly up regulated when the cells were transfected with Sp1 plasmid as compared to Sp1 inhibitor (2,4,5 trifluoroaniline) treated cells at both transcription and translation levels. MMP-2 and MMP-9 levels were found to be significantly elevated when the cells were subjected to NaHS [sodium hydrogen sulphide (H2S donor)] treatment as compared to AOAA (aminooxyacetic acid) treated cells.

Conclusion

This is the first study which implies that miR-22 via targeting Sp1 must have influenced the mRNA and protein expression of CBS, MMP-2 and MMP-9 in order to regulate the trophoblast invasion.
Mindfulness Training and Health-Related Quality of Life in Male NCAA Division I Athletes
Authors: Haraldsdottir Kristin , Anderson Scott , Sanfilippo Jennifer , McGehee Chad , Watson Andrew M
Published: March 2023

Objective

To examine the effects of a mindfulness intervention on mental and physical quality of life (QOL) among male collegiate athletes.

Participants

327 male Division I collegiate athletes.

Methods

QOL was measured among 527 participants using the Veterans Rand-12 survey twice annually from 2017-2020. 101 athletes underwent 6-week mindfulness training in spring 2019. The influence of mindfulness on mental and physical QOL scores (MCS, PCS) was evaluated using linear mixed effects models with season (winter, summer), group (mindfulness, control), time (pre/post-intervention) and time*group interaction as fixed effects and individual as a random effect.

Results

PCS was associated with the interaction between time and group (β=1.05±0.51, p=0.04) and season (β=-0.80±0.24, p=0.001), but not time (β=-0.40±0.37, p=0.27) or group (β=0.43±0.44, p=0.33).

Conclusion

Mindfulness training is associated with improved physical QOL among male collegiate athletes, but did not appear to be associated with differences in mental QOL.
Single-cell transcriptional profiling in Arabidopsis root exposed to B toxicity at seedling stages
Authors: Yılmaz Hikmet , Kayıhan Ceyhun , Ünal Halis Batuhan , Yaprak Oğuzhan , Aksoy Emre
Published: March 2023

Cell-specific transcriptional responses to environmental stimuli are yet to be fully characterized in plants. In this study, we apply single-cell RNA sequencing toArabidopsis thalianaroots exposed to boron (B) toxicity to characterize the transcription map at cellular resolution and thus, to understand how B toxicity can alter gene expression and development at single cell resolution. Single-cell transcriptomes from protoplasts of more than 2750Arabidopsis thalianaroot cells were obtained. Plotting the single-cell transcriptomes via t-SNE projections yielded six major cell clusters including quiescent cells (QC), endodermis, cortex, columella, trichoblast (root-hair), and root cap. The maximum number of most significantly upregulated genes were determined in columella under 1 mM B and in endodermis under 2 mM B condition. Additionally, the maximum number of most significantly upregulated genes under 3 mM B and 5 mM B conditions was determined in the root cap, implying a critical role against severe B toxicity conditions. We also showed that these upregulated genes are highly correlated with “glutathione metabolism” in columella and “carbon metabolism” in root cap. Taken together, for the first time in the literature, our study provides a gene expression map at single-cell resolution and describes the extent of heterogeneity at the molecular level among populations of different cell types in Arabidopsis root under B toxicity conditions.
A genotype-phenotype taxonomy of hypertrophic cardiomyopathy
Authors: Curran Lara , de Marvao Antonio , Inglese Paolo , McGurk Kathryn A , Schiratti Pierre-Raphaël , Clement Adam , Zheng Sean L , Li Surui , Pua Chee Jian , Shah Mit , Jafari Mina , Theotokis Pantazis , Buchan Rachel J , Jurgens Sean J , Raphael Claire E , Baksi Arun John , Pantazis Antonis , Halliday Brian P , Pennell Dudley J , Bai Wenjia , Chin Calvin W L , Tadros Rafik , Bezzina Connie R , Watkins Hugh , Cook Stuart A , Prasad Sanjay K , Ware James S , O’Regan Declan P
Published: March 2023

Background

Hypertrophic cardiomyopathy (HCM) is an important cause of sudden cardiac death associated with heterogeneous phenotypes but there is no systematic framework for classifying morphology or assessing associated risks. Here we quantitatively survey genotype-phenotype associations in HCM to derive a data-driven taxonomy of disease expression.

Methods

We enrolled 436 HCM patients (median age 60 years; 28.8% women) with clinical, genetic and imaging data. An independent cohort of 60 HCM patients from Singapore (median age 59 years; 11% women) and a reference population from UK Biobank (n = 16,691, mean age 55 years; 52.5% women) were also recruited. We used machine learning to analyse the three-dimensional structure of the left ventricle from cardiac magnetic resonance imaging and build a tree-based classification of HCM phenotypes. Genotype and mortality risk distributions were projected on the tree.

Results

Carriers of pathogenic or likely pathogenic variants for HCM (P/LP) variants had lower left ventricular mass, but greater basal septal hypertrophy, with reduced lifespan (mean follow-up 9.9 years) compared to genotype negative individuals (hazard ratio: 2.66; 95% confidence interval [CI]: 1.42-4.96;P< 0.002). Four main phenotypic branches were identified using unsupervised learning of three-dimensional shape: 1) non-sarcomeric hypertrophy with co-existing hypertension; 2) diffuse and basal asymmetric hypertrophy associated with outflow tract obstruction; 3) isolated basal hypertrophy; 4) milder non-obstructive hypertrophy enriched for familial sarcomeric HCM (odds ratio for P/LP variants: 2.18 [95% CI: 1.93-2.28,P= 0.0001]). Polygenic risk for HCM was also associated with different patterns and degrees of disease expression. The model was generalisable to an independent cohort (trustworthinessM1: 0.86-0.88).

Conclusions

We report a data-driven taxonomy of HCM for identifying groups of patients with similar morphology while preserving a continuum of disease severity, genetic risk and outcomes. This approach will be of value in understanding the causes and consequences of disease diversity.
Protocol of a Study to Benchmark Occupational Health and Safety in Japan: W2S-Ohpm Study
Authors: Nagata Tomohisa , Odagami Kiminori , Nagata Masako , Adi Nuri Purwito , Mori Koji
Published: March 2023

We aim to conduct a prospective cohort study to benchmark occupational health and safety in Japan. Here, we describe the detailed protocol for the baseline survey based on the Checklist for Reporting Results of Internet E-Surveys. We conducted the baseline survey for the prospective cohort study in 2022. Our target population was workers in Japan aged 20 years or older, who we sampled to be representative of the Japanese workforce, stratified by sex, age, and region. Among 59,272 registered monitors who answered the initial screening questions, 29,997 completed the survey. After excluding 2,304 invalid responses, we used 27,693 valid participants in our final analysis. The number and mean age of men were 15,201 (55%) and 46 years; those of women were 12,492 (45%) and 45 years. With respect to sex, age, and regional composition, our sampling was representative of Japan’s working population. Our sampling for employment status and industry yielded almost the same proportions as a government-led representative sampling of workers in Japan.
Temporal effects of sugar intake on fly local search and honey bee dance behaviour
Authors: Shakeel Manal , Brockmann Axel
Published: March 2023

Honey bees communicate navigational information of profitable food to nestmates via dance, a small scale walking pattern. Hungry flies and honey bee foragers initiate a sugar-elicited local search that involves path integration and show similarities with dance behaviour. Using a comparative approach, we explored the temporal dynamics of initiation of local search and dance in flies and honey bees, respectively. Passive displacement experiments showed that feeding and initiation of search can be spatially dissociated in both species. Sugar intake increased the probability to initiate a search but onset of walking starts the path integration system guiding the search. When prevented from walking, the motivation to begin a path integration-based search was sustained for 3 min after sugar intake in flies and bees. In flies, the behavioural parameters of search were significantly reduced for 3 min but were higher than flies that were given no sugar stimulus, indicating some degree of meander. These results suggest that sugar elicits two independent behavioural responses: path integration and increased turning, and initiation and duration of path integration system is temporally more restricted. Honey bee dance experiments demonstrated that the motivation of foragers to initiate dance was sustained for 15 min, whereas the number of circuits declined after 3 min. Based on our findings, we propose that the food-intake during foraging has the capability to activate the path integration system in flies and honey bees, and this interaction might have been elaborated during evolution to guide the walking pattern of the honey bee dance.
Sinorhizobium melilotiFcrX coordinates cell cycle and division during free-living growth and symbiosis
Authors: Dendene Sara , Xue Shuanghong , Nicoud Quentin , Valette Odile , Frascella Angela , Bonnardel Anna , Le Bars Romain , Bourge Mickaël , Mergaert Peter , Brilli Matteo , Alunni Benoît , Biondi Emanuele G.
Published: March 2023

Sinorhizobium melilotiis a soil bacterium that establishes a symbiosis within root nodules of legumes (Medicago sativa, for example) where it fixes atmospheric nitrogen into ammonia and obtains in return carbon sources and other nutrients. In this symbiosis,S. melilotiundergoes a drastic cellular change leading to a terminal differentiated form (called bacteroid) characterized by genome endoreduplication, increase of cell size and high membrane permeability. The bacterial cell cycle (mis)regulation is at the heart of this differentiation process. In free-living cells, the master regulator CtrA ensures the progression of cell cycle by activating cell division (controlled by the tubulin-like protein FtsZ) and simultaneously inhibiting supernumerary DNA replication, while on the other hand the downregulation of CtrA and FtsZ is essential for bacteroid differentiation during symbiosis, preventing endosymbiont division and permitting genome endoreduplication. Little is known inS. melilotiabout regulators of CtrA and FtsZ, as well as the processes that control bacteroid development. Here, we combine cell biology, biochemistry and bacterial genetics approaches to understand the function(s) of FcrX, a new factor that controls both CtrA and FtsZ, in free-living growth and in symbiosis. Depletion of the essential genefcrXled to abnormally high levels of FtsZ and CtrA and minicell formation. Using multiple complementary techniques, we showed that FcrX is able to interact physically with FtsZ and CtrA. Moreover, its transcription is controlled by CtrA itself and displays an oscillatory pattern in the cell cycle. We further showed that, despite a weak homology with FliJ-like proteins, only FcrX proteins from closely-related species are able to complementS. meliloti fcrXfunction. Finally, deregulation of FcrX showed abnormal symbiotic behaviors in plants suggesting a putative role of this factor during bacteroid differentiation. In conclusion, FcrX is the first known cell cycle regulator that acts directly on both, CtrA and FtsZ, thereby controlling cell cycle, division and symbiotic differentiation.
First crystal structure of double knotted protein TrmD-Tm1570 – inside from degradation perspective
Authors: da Silva Fernando Bruno , Lewandowska Iwona , Kluza Anna , Niewieczerzal Szymon , Augustyniak Rafał , Sulkowska Joanna I.
Published: March 2023

Herein, we present the first crystal structure of a double knotted protein TrmD-Tm1570 fromCalditerrivibrio nitroreducens, as well the X-ray structure of each sub-domain. The protein consists of two domains TrmD and Tm1570, each embedding a single trefoil knot, which can function on their own. TrmD-Tm1570 forms a compact homodimeric complex. This protein represents one of 296 possible doubly knotted proteins from SPOUT family. Based on TrmD-Tm1570 fromCalditerrivibrio nitroreducenswe show that a double knotted protein can be fully degraded by the ClpXP degradation system, as well as its individual domains. We used numerical simulations to explain the difference in the speed of degradation. The derived kinetic parameters for the degradation process are comparable to the experimental data found for unknotted polypeptide chains.
The maizePLASTID TERMINAL OXIDASE(PTOX) gene controls the carotenoid content of kernels
Authors: Nie Yongxin , Wang Hui , Zhang Guan , Ding Haiping , Han Beibei , Liu Lei , Shi Jian , Du Jiyuan , Li Xiaohu , Li Xinzheng , Zhao Yajie , Zhang Xiaocong , Liu Changlin , Weng Jianfeng , Li Xinhai , Zhang Xiansheng , Zhao Xiangyu , Pan Guangtang , Jackson David , Wu Qingyu , Zhang Zhiming
Published: March 2023

Carotenoids perform a broad range of important functions in humans; therefore, carotenoid biofortification of maize (Zea maysL.), one of the most highly produced cereal crops worldwide, would have a global impact on human health.

PLASTID TERMINAL OXIDASE(PTOX) genes play an important role in carotenoid metabolism; however, the possible function ofPTOXin carotenoid biosynthesis in maize has not yet been explored. In this study, we identified the maizePTOXgeneZmPTOX1by forward genetic screening.

While most higher plant species possess a single copy of thePTOXgene, maize carries two tandemly duplicated copies ofZmPTOX. Characterization ofZmptox1mutants revealed that disrupting one copy ofZmPTOX1was enough to impair carotenoid biosynthesis, indicating thatZmPTOX1is essential for carotenoid biosynthesis in maize kernels. Remarkably, overexpression ofZmPTOX1significantly improved the content of carotenoids, especially β-carotene (provitamin A), which was increased by ~3-fold, in maize kernels.

Overall, our study shows thatZmPTOX1plays a crucial role in carotenoid biosynthesis in maize kernels and suggests that fine-tuning the expression of this gene could improve the nutritional value of cereal grains.
Distilling identifiable and interpretable dynamic models from biological data
Authors: Massonis Gemma , Villaverde Alejandro F. , Banga Julio R.
Published: March 2023

Mechanistic dynamical models allow us to study the behavior of complex biological systems. They can provide an objective and quantitative understanding that would be difficult to achieve through other means. However, the systematic development of these models is a non-trivial exercise and an open problem in computational biology. Currently, many research efforts are focused on model discovery, i.e. automating the development of interpretable models from data. One of the main frameworks is sparse regression, where the sparse identification of nonlinear dynamics (SINDy) algorithm and its variants have enjoyed great success. SINDy-PI is an extension which allows the discovery of rational nonlinear terms, thus enabling the identification of kinetic functions common in biochemical networks, such as Michaelis-Menten. SINDy-PI also pays special attention to the recovery of parsimonious models (Occam’s razor). Here we focus on biological models composed of sets of deterministic nonlinear ordinary differential equations. We present a methodology that, combined with SINDy-PI, allows the automatic discovery of structurally identifiable and observable models which are also mechanistically interpretable. The lack of structural identifiability and observability makes it impossible to uniquely infer parameter and state variables, which can compromise the usefulness of a model by distorting its mechanistic significance and hampering its ability to produce biological insights. We illustrate the performance of our method with six case studies. We find that, despite enforcing sparsity, SINDy-PI sometimes yields models that are unidentifiable. In these cases we show how our method transforms their equations in order to obtain a structurally identifiable and observable model which is also interpretable.

Author summary

Dynamical models provide a quantitative understanding of complex biological systems. Since their development is far from trivial, in recent years many research efforts focus on obtaining these models automatically from data. One of the most effective approaches is based on implicit sparse regression. This technique is able to infer biochemical networks with kinetic functions containing rational nonlinear terms. However, as we show here, one limitation is that it may yield models that are unidentifiable. These features may lead to inaccurate mechanistic interpretations and wrong biological insights. To overcome this limitation, we propose an integrated methodology that applies additional procedures in order to ensure that the discovered models are structurally identifiable, observable, and interpretable. We demonstrate our method with six challenging case studies of increasing model complexity.
A single base pair duplication inSLC33A1gene causes fetal losses and neonatal lethality in Manech Tête Rousse dairy sheep
Authors: Ben Braiek Maxime , Szymczak Soline , André Céline , Bardou Philippe , Fidelle Francis , Granado-Tajada Itsasne , Plisson-Petit Florence , Sarry Julien , Woloszyn Florent , Moreno-Romieux Carole , Fabre Stéphane
Published: March 2023

Recently, we evidenced that the Manech Tête Rousse (MTR) deficient homozygous haplotype 2 (MTRDHH2) was likely to harbor a recessive lethal variant in ovine. In the present study, we fine mapped this region by analyzing the whole genome sequence of five MTRDHH2 heterozygous carriers compared to 95 sequences of non-carrier animals from MTR and others ovine breeds. We successfully identified a single base pair duplication in theSLC33A1gene, resulting in a frameshift leading to a premature stop codon (p.Arg246Alafs*3). SLC33A1 acts as a transmembrane transporter of acetyl-Coenzyme A, essential for cellular metabolism. In order to assess for the lethal phenotype in homozygous MTR sheep, we generated at-risk matings by artificial insemination (AI) between rams and ewes heterozygous for theSLC33A1variant namedSLC33A1_dupG. Gestation status was checked 15 days post-AI by a molecular test from blood expression of the interferon Tau-stimulatedMX1gene, and by ultrasonography performed between 45 days and 60 days post-AI. Based on ultrasonography, the AI success was reduced by 12% compared to safe matings suggesting embryonic/fetal losses further confirmed by the molecular test based onMX1differential expression. Forty-nine lambs were born from at-risk matings with a mortality rate of 34.7% observed before weaning. HomozygousSLC33A1_dupG lambs contributed to 47% of this mortality occurring mainly in the first five days after lambing with no obvious clinical signs. Thus, an appropriate management ofSLC33A1_dupG (allele frequency of 0.04) in the MTR selection scheme should increase the overall fertility and lamb survival.
Non-invasive vagus nerve stimulation and the motivation to work for rewards: a replication
Authors: Lucchi Federica , Lloyd Beth , Nieuwenhuis Sander
Published: March 2023

Background

The vagus nerve is thought to be involved in the allostatic regulation of motivation and energy metabolism via gut-brain interactions. A recent study by Neuser and colleagues [1] provided novel evidence for this process in humans, by reporting a positive effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the invigoration of reward-seeking behaviors, especially for food rewards.

Objective

We conducted an independent direct replication of Neuser et al. [1], to assess the robustness of their findings.

Methods

Following the original study, we used a single-blind, sham-controlled, randomized cross-over design. We applied left-sided taVNS in healthy human volunteers (n=40), while they performed an effort allocation task in which they had to work for monetary and food rewards. The replication study was purely confirmatory in that it strictly followed the analysis plans and scripts used by Neuser et al. [1].

Results

Although, in line with Neuser et al. [1], we found strong effects of task variables on effort invigoration and effort maintenance, we failed to replicate their key finding: taVNS did not increase the strength of invigoration (p= .62); the data were five times more likely (BF10= 0.19) under the null hypothesis. We also found substantial evidence against an effect of taVNS on effort maintenance (p= 0.50; BF10= 0.20).

Conclusions

Our results provide evidence against the idea that taVNS boosts the motivational drive to work for rewards. Our study also highlights the need for direct replications of influential taVNS studies.