bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Biocontrol Microorganisms Causing Attenuated Pathogenicity in Plasmopara viticola
Authors: Shi Xiaomeng , Shen Hongmiao , Wang Yacong , Yang Xue , Shi Ruolin , Tan Wanzhong , Ran Longxian
Published: January 2024

A phenomenon of pathogenicity attenuation of Plasmopara viticola was consistently observed during its subculture on grape. To clarify the causes of attenuated pathogenicity of P. viticola, culturable microbes were isolated from the P. viticola mass (mycelia, sporangiophores, and sporangia) in each generation and tested for their biocontrol efficacies on grape downy mildew (GDM). The results showed that the incidence of GDM decreased with the increase in the number of subculture times on both vineyard-collected leaves and grape leaves from in vitro-grown seedlings. The number of culturable microbial taxa on the surface of P. viticola decreased, whereas the population densities of four specific strains (i.e., K2, K7, P1, and P5) increased significantly with the increase in subculture times. Compared with the control, the biocontrol efficacies of the bacterial strain K2 reached 87.5%, and those of both fungal strains P1 and P5 reached 100.0%. Based on morphological characteristics and molecular sequences, strains K2, P1, and P5 were identified as Curtobacterium herbarum, Thecaphora amaranthi, and Acremonium sclerotigenum, respectively, and these three strains survived very well and multiplied on the surface of P. viticola. As the number of times P. viticola was subcultured increased, all three of these strains became the predominant strains, leading to greater P. viticola inhibition, attenuated P. viticola pathogenicity, and effective GDM biological control. To the best of our knowledge, this is the first report of C. herbarum and T. amaranthi having biological control activity against GDM.
Zone 2 5th Metatarsal Fractures Treated Nonoperatively Have Similar Time to Healing to Those Treated Operatively
Authors: Kadiyala Manasa L. , Kingery Matthew T. , Hamzane Mohamed , Walls Raymond , Ganta Abhishek , Konda Sanjit R. , Egol Kenneth A.
Published: January 2024

OBJECTIVES:

To quantify the rate of union and time to clinical and radiographic healing in Zone 2 proximal 5th metatarsal (MT) fractures and compare these outcomes between Zone 2 fractures treated operatively and nonoperatively.

METHODS:

Design:

Retrospective cohort study

Setting:

Academic Level I Trauma Center

Patient Selection Criteria:

Patients with 5th metatarsal fractures who presented between December 2012 and April 2022 and confirmed to have Zone 2 fractures (defined as fractures entering the proximal 4-5 MT articulation on the oblique radiographic view) were included in the study analysis in either the operative or nonoperative cohort.

Outcome Measures and Comparisons:

Nonunion, time to clinical healing by, and time to radiographic healing between operative and nonoperative treatment

RESULTS:

Among the 499 included patients, 475 patients (95.2%) were initially treated nonoperatively, and 24 patients (4.8%) were treated operatively. Both groups were similar in demographics (Table 1). There was no difference in the proportion of patients with nonunions between groups (6.1% in the nonoperative group versus 3.8% in the operative group, p = 1.000). Additionally, there was no statistically significant difference between groups with respect to the time to clinical healing by (9.9 +/- 8.3 weeks for the nonoperative group versus 15.4 +/- 15.0 weeks for the operative group, p = 0.117) or the time to radiographic healing by (18.7 +/- 12 weeks for the nonoperative group versus 18.5 +/- 16.6 weeks for the operative group, p = 0.970) (Table 2).

CONCLUSIONS:

Zone 2 5th metatarsal base fractures were successfully treated with nonoperative management. There was no evidence in this study that operative treatment leads to significantly faster clinical or radiographic healing.
Two novel deep-learning models to predict spontaneous ureteral calculi passage: Model development and validation
Authors: Xiao Zhiying , Bai Hui , Zhang Yumeng
Published: January 2024

Objective

The aim of this study was to develop and evaluate two deep-learning (DL) models for predicting spontaneous ureteral stone passage (SSP).

Materials and methods

A total of 1217 patients with thin-layer computed tomography–confirmed ureteral stones in our hospital from January 2019 to December 2022 were retrospectively examined. These patients were grouped into 3 data sets: the training set (n = 1000), the validation set (n = 100), and the test set (n = 117). Two DL models based on residual neural network (ResNet)—2-dimensional (2D) ResNet29 and 3-dimensional (3D) ResNet29—were separately developed, trained, and assessed. The predictive ability of a conventional approach using a stone diameter of <5 mm on computed tomography was investigated, and the results were compared with those of the two DL models.

Results

Of the 1217 patients, SSP was reported in 446 (36.6%). The total accuracy, sensitivity, and specificity were 76.9%, 56.1%, and 90.8% for the stone diameter approach; 87.1%, 84.2%, and 92.7% for the 2D ResNet29 model; and 90.6%, 88.2%, and 95.1% for the 3D ResNet29 model, respectively. Both the 2D and 3D ResNet29 models showed significantly higher accuracy than the stone diameter approach. Receiver operating characteristic curve analysis showed that both DL models had a significantly higher area under the curve than the stone diameter–based classification.

Conclusions

The DL models, particularly the 3D model, are novel and effective methods for predicting SSP rates. Using such models may help determine whether a patient should receive surgical intervention or expect a long interval before stone passage.
Comparison of recovery profiles between total intravenous anaesthesia with propofol or remimazolam reversed with flumazenil in patients undergoing breast surgery
Authors: Lee Jaemoon , Kim Dong Hyouk , Ju Jae-Woo , Nam Karam , Cho Youn Joung , Jeon Yunseok , Lee Seohee
Published: January 2024

BACKGROUND

Remimazolam, a short acting benzodiazepine, is being used for general anaesthesia. The results of studies comparing recovery after propofol with that of remimazolam are inconsistent. Given that flumazenil reverses the sedative effects of remimazolam, we hypothesised that it would speed up recovery from remimazolam general anaesthesia.

OBJECTIVES

The aim of this trial was to compare the speed of recovery from general anaesthesia between propofol and remimazolam reversed with flumazenil in patients undergoing minimally invasive breast surgery.

DESIGN

Randomised, single-centre, double-blind controlled trial.

SETTING

A tertiary teaching hospital in South Korea from August 2022 to December 2022.

PATIENTS

Adult patients (≥19 years of age) about to undergo general anaesthesia for scheduled breast cancer surgery.

INTERVENTIONS

Patients were randomly allocated to either the propofol or the remimazolam/flumazenil group. The emergence process was monitored by only one anaesthesiologist.

MAIN OUTCOME MEASURES

The primary outcome was the time to eye opening to command during recovery from the general anaesthesia. Time to removal of the supraglottic airway (SGA) time to discharge, and the Riker sedation agitation scale (SAS) score (1 to 4) during emergence were compared as secondary outcomes.

RESULTS

The remimazolam group had a significantly shorter mean time to eye opening than the propofol group [127 ± 51 vs. 314 ± 140 s; mean difference 187 s (95% confidence interval (CI), 133 to 241 s; P < 0.001]. The remimazolam group also had shorter times to SGA removal [169 ± 51 vs. 366 ± 149 s; mean difference 198 s (95% CI, 140 to 255 s); P < 0.001] and time to discharge from the operating room [243 ± 55 vs. 449 ± 159 s; mean difference 206 s (95% CI, 145 to 267 s); P < 0.001]. The SAS scores during emergence also differed significantly, with 1 patient in the propofol group and 25 in the remimazolam group attaining scores of 4 (P < 0.001).

CONCLUSION

Administration of remimazolam with flumazenil may be a promising option for patients undergoing breast cancer surgery, providing faster recovery and better SAS scores than propofol during emergence from general anaesthesia.

TRIAL REGISTRATION

ClinicalTrials.gov (NCT05435911).
Update on syphilis in pregnancy: marrying basic science advances and clinical perseverance to solve an ancient public health problem
Authors: Adhikari Emily H.
Published: January 2024

Purpose of review

While the clinical disease of syphilis, its consequences in pregnancy, and its sensitivity to penicillin treatment have remained relatively unchanged for a century or more, new technologies and basic discoveries in syphilis research have translated into tangible advances in clinical diagnosis, treatment, and prevention. The purpose of this review is to help the reader understand some of the recent relevant scientific publications on syphilis and its causative organism in a clinical obstetric context.

Recent findings

Rates of adult and congenital syphilis have risen dramatically in the last decade despite public health efforts. Penicillin shortages and lack of screening or adequate treatment have all contributed to global disease burden. Advances in genomic and microbiological characterization of this spirochete have led to new developments in serologic and molecular diagnosis as well as evaluation of potential vaccine candidates. Until a syphilis vaccine is available, substance use disorders and lack of screening in pregnancy are associated with increased congenital syphilis, and these challenges will require novel solutions to fully address this public health crisis.

Addressing the burden of congenital syphilis demands that obstetricians stay well informed of new tools and resources for diagnosis, treatment, and prevention of syphilis now and in the future.
Myeloid spatial and transcriptional molecular signature of ischemia-reperfusion injury in human liver transplantation
Authors: Sosa Rebecca A. , Ahn Richard , Li Fang , Terry Allyson Q. , Qian Zach , Bhat Adil , Sen Subha , Naini Bita V. , Ito Takahiro , Kaldas Fady M. , Hoffmann Alexander , Busuttil Ronald W. , Kupiec-Weglinski Jerzy W. , Gjertson David W. , Reed Elaine F.
Published: January 2024

Background:

Ischemia-reperfusion injury (IRI) is a significant clinical concern in liver transplantation, with a key influence on short-term and long-term allograft and patient survival. Myeloid cells trigger and sustain tissue inflammation and damage associated with IRI, but the mechanisms regulating these activities are unknown. To address this, we investigated the molecular characteristics of intragraft myeloid cells present in biopsy-proven IRI− and IRI+ liver transplants.

Methods:

RNA-sequencing was performed on 80 pre-reperfusion and post-reperfusion biopsies from 40 human recipients of liver transplantation (23 IRI+, 17 IRI−). We used transcriptional profiling and computational approaches to identify specific gene coexpression network modules correlated with functional subsets of MPO+, lysozyme+, and CD68+ myeloid cells quantified by immunohistochemistry on sequential sections from the same patient biopsies.

Results:

A global molecular map showed gene signatures related to myeloid activation in all patients regardless of IRI status; however, myeloid cell subsets differed dramatically in their spatial morphology and associated gene signatures. IRI− recipients were found to have a natural corticosteroid production and response profile from pre-reperfusion to post-reperfusion, particularly among monocytes/macrophages. The pre-reperfusion signature of IRI+ recipients included acute inflammatory responses in neutrophils and increased translation of adaptive immune-related genes in monocytes/macrophages coupled with decreased glucocorticoid responses. Subsequent lymphocyte activation at post-reperfusion identified transcriptional programs associated with the transition to adaptive immunity found only among IRI+ recipients.

Conclusions:

Myeloid subset-specific genes and related signaling pathways provide targets for the development of therapeutic strategies aimed at limiting IRI in the clinical setting of liver transplantation.
Comparison of 2 Different Treatments for Conjunctivochalasis: Plasma-Based Conjunctivoplasty Versus Argon Laser Photocoagulation
Authors: Ucar Fikret , Unluzeybek Murat
Published: January 2024

Purpose:

The aim of this study was to compare the clinical outcomes of plasma-based conjunctivoplasty and argon laser photocoagulation techniques used in the treatment of conjunctivochalasis.

Methods:

The study included 119 eyes from 67 patients who underwent plasma-based conjunctivoplasty or argon laser photocoagulation for conjunctivochalasis in our clinic between February 2021 and March 2022. Group 1 included 62 eyes from 35 patients who had plasma-based conjunctivoplasty. Group 2 included 57 eyes from 32 patients who had argon laser photocoagulation. Main outcomes were patient symptoms, the degree of conjunctivochalasis, fluorescein staining score, tear breakup time, the amount of conjunctival shrinkage, and complications.

Results:

Before surgery, Group 1 had grade 1 conjunctivochalasis in 8 eyes (12.9%), grade 2 in 20 eyes (32.2%), and grade 3 in 34 eyes (54.8%). In Group 2, 9 eyes (15.7%) had grade 1, 21 eyes (36.8%) had grade 2, and 27 eyes (47.3%) had grade 3 conjunctivochalasis (P = 0.43). At the sixth postoperative month, only 2 eyes (3.2%) in Group 1 had grade 1 conjunctivochalasis, whereas the other cases (96.7%) had no conjunctivochalasis. However, Group 2 had grade 1 conjunctivochalasis in 16 eyes (28.0%), grade 2 in 21 eyes (36.8%), and grade 3 in 2 eyes (3.5%). Conjunctival shrinkage in Group 1 (5.1 ± 1.2 mm) was significantly higher than in Group 2 (3.3 ± 0.9 mm; P < 0.001). Postoperative tear breakup time in Group 1 (10.2 ± 2.1 seconds) was significantly longer than in Group 2 (8.8 ± 2.0 seconds; P < 0.001).

Conclusions:

Plasma-based conjunctivoplasty demonstrated greater clinical improvement and efficacy than argon laser photocoagulation for the treatment of conjunctivochalasis.
Implementation of optical coherence tomography in retinopathy of prematurity screening
Authors: Hanif Adam M. , Jian Yifan , Young Benjamin K. , Campbell John Peter
Published: January 2024

Purpose of review

In this review, we explore the investigational applications of optical coherence tomography (OCT) in retinopathy of prematurity (ROP), the insights they have delivered thus far, and key milestones for its integration into the standard of care.

Recent findings

While OCT has been widely integrated into clinical management of common retinal diseases, its use in pediatric contexts has been undermined by limitations in ergonomics, image acquisition time, and field of view. Recently, investigational handheld OCT devices have been reported with advancements including ultra-widefield view, noncontact use, and high-speed image capture permitting real-time en face visualization. These developments are compelling for OCT as a more objective alternative with reduced neonatal stress compared to indirect ophthalmoscopy and/or fundus photography as a means of classifying and monitoring ROP.

OCT may become a viable modality in management of ROP. Ongoing innovation surrounding handheld devices should aim to optimize patient comfort and image resolution in the retinal periphery. Future clinical investigations may seek to objectively characterize features of peripheral stage and explore novel biomarkers of disease activity.
“You Are in the Middle of a Road, a Road With No End”: Experiences of Women Who Underwent Medical Termination of Their Pregnancies
Authors: Akın Işık Rabiye , İş Mine , Kaya Yunus
Published: January 2024

This article focused on the experiences of women who underwent medical termination of their pregnancies. The study adopted a qualitative phenomenological research design with a sample of 20 pregnant women. Data were collected between April and June 2022 using a personal information form and a semistructured individual interview. The qualitative data were analyzed into 4 categories: “psychosocial impacts,” “impacts on functionality,” “coping,” and “expectations.” These categories comprised 8 themes and 24 subthemes. Nurses play a crucial role in adopting family-centered approaches to offer holistic care. They should prioritize providing physical care throughout the medical termination, while also assessing the psychological impact of fetal loss. Perinatal palliative care and bereavement counseling should be integrated into care practices.
The Experiences of Nurses as Double-Duty Caregivers for a Family Member at the End of Life
Authors: Basley Sandra A. , Ferszt Ginette G. , DeSanto-Madeya Susan
Published: January 2024

Increasing numbers of individuals with complex, advanced illnesses are living longer and being cared for in the home by family members. As a result, family caregivers often experience physical, emotional, psychological, and social distress. A unique subset of this population are nurses who find themselves providing care in both their family lives and work lives, a phenomenon known as “double-duty caregiving.” This study explored the experiences of nurses providing end-of-life care for family members while continuing to work as a nurse and the consequences of this experience. A qualitative design, using semistructured, in-depth interviews, was used to capture the double-duty caregivers' experiences. Four overarching themes were identified: It Takes a Village, Driving the Bus, Juggling Many Hats, and Moving Through and Looking Back. These themes captured the components of a support system that are essential for the double-duty caregiver to perform this work, the multifaceted expectations placed upon the double-duty caregiver, the double-duty caregiver's relentless need to balance multiple roles, and the immediate and long-term impact of double-duty caregiving. As nurses, we must acknowledge the need for self-care during this experience, and as a profession, we must provide support for the double-duty caregiver to preserve their personal and professional well-being.
The Effect of the Timing of Cold Application on Pain and Satisfaction in Patients With Fractures
Authors: Kırıcı Derya , Oral Semra Erdağı
Published: January 2024

This experimental study used a repeated-measures design to examine the effect of the timing of cold application on pain and satisfaction in a sample of 60 patients who had fracture surgery. Cold was applied for 20 minutes each hour for four hours to patients assigned to the experimental group. Whereas cold was applied once to those in the control group: for 20 minutes during the first hour after surgery. Results following data analysis from repeated measurements of pain before and after cold application in both groups showed a significant difference between the groups (p < .05). Patients' levels of satisfaction with nursing care practice were higher in the experimental group than in the control group, although not significantly (p > .05). The pain score in the experimental group decreased significantly with each cold application. In the control group, the pretreatment pain score decreased significantly after one cold application, increasing again in 3 hours without cold application. These findings are important for nurses caring for postoperative patients and giving discharge instructions. Our findings suggest repeated cold applications for 20 minutes at hourly intervals may result in better overall pain reduction than a single cold application.
The Effects of Long-Term Walking Exercise on Structural Progression, Symptoms, and Extensor Muscle Strength in Patients with Mild or at High Risk of Knee Osteoarthritis: Data from the Osteoarthritis Initiative
Authors: Zhang Hui , Wang Junqing , Shuai Tao , Li Kang , Nie Yong
Published: January 2024

Objective

To assess the relationship between walking exercise and medial joint space narrowing (JSN) progression, symptoms, and knee extensor muscle strength (EMS) in early knee osteoarthritis (OA) patients.

Methods

This nested cohort study within the Osteoarthritis Initiative included participants aged 50 and above with knee OA (Kellgren-Lawrence grades 0-2). Walking exercisers were identified using a modified Historical Physical Activity Survey Instrument. Differences in medial JSN, Knee Injury and Osteoarthritis Outcome Score (KOOS), and knee EMS were evaluated through the three-way ANOVA.

Results

Among 896 participants, 83.4% reported walking exercise. Female walkers showed significant improvements in symptoms (KOOS-Pain: P < 0.001; KOOS-Symptom: P < 0.001; KOOS-Quality of Life (QOL): P < 0.001; KOOS-Function, Sports, and Recreational Activities (FSR): P = 0.007). Similar results were observed in male walkers (KOOS-Pain: P < 0.001; KOOS-Symptom: P < 0.001; KOOS- QOL: P = 0.001; KOOS- FSR: P = 0.009). Walkers showed significantly increased knee EMS at 24 months (Female: P < 0.001; Male: P = 0.003). Female non-walkers had significantly decreased knee EMS at 24 months (P < 0.001). Walkers showed significant improvement in medial JSN (OR = 1.1, 95% CI: 1.0 to 1.2) and KL grade (OR = 1.0, 95% CI: 1.0 to 1.1) compared to non-walkers.

Conclusion

Walking exercise prevents structural progression and improves symptoms. Meanwhile, the increased knee EMS in all walkers further supports the validity of recommending walking exercises for early-stage knee OA patients.
Are your patients safe to mobilize alone in their room? The Johns Hopkins Hospital In-Room Independence Scale (JH-IRIS)
Authors: Reoli Rachel , Wilkins Erik , Klag Julia , Hoyer Erik , Lavezza Annette
Published: January 2024

Objective

Given the stigma of falls while hospitalized, inpatient rehabilitation facilities (IRF) often restrict the independent room mobility of their patients. We assessed the psychometric properties of a new tool, the Johns Hopkins In-Room Independence Scale (JH-IRIS), to evaluate its effectiveness at identifying independence for in-room mobility.

Design

Construct validity was assessed by comparing the JH-IRIS to its “gold standard” counterparts, The Johns Hopkins Falls Risk Assessment Tool (JHFRAT), the Activity Measure for Post-Acute Care (AM-PAC) Mobility and Activity, and the Centers for Medicare Quality Indicators (QI). Reliability was assessed via Cronbach’s Alpha.

Results

197 episodes were included. Construct validity: JH-IRIS had significantly negative low correlation to the JHFRAT (Spearman’s Rho –0.281), and a significant moderate correlation to the AM-PAC Activity and AM-PAC Mobility (Spearman’s Rho, 0.678 and 0.530, respectively). The JH-IRIS was moderately positively correlated to the QIs for mobility and activity (Spearman’s Rho 0.577 and 0.643, respectively). All two tailed, alpha level 0.01. JH-IRIS' reliability was strong (Cronbach’s Alpha 0.822, 15 items). Sensitivity and specificity were both 100%.

Conclusion

Given the moderate validity, strong reliability, and high sensitivity/specificity, our study suggests the JH-IRIS can be used to identify patients who have the capacity to mobilize independently in their room.
Characteristics and Methodological Quality of the Top 50 Most Influential Articles on Stroke Rehabilitation: A Bibliometric Analysis
Authors: Ogihara Hirofumi , Yamamoto Norio , Kurasawa Yasuyuki , Kamo Tomohiko , Hagiyama Akikazu , Hayashi Shota , Momosaki Ryo
Published: January 2024

This study aimed to conduct a comprehensive review of the top 50 most influential articles on stroke rehabilitation to investigate characteristics such as the number of citations, year of publication, study design, and research topic, as well as to assess the evidence level and methodological quality. Moreover, we performed a supplementary assessment of the top ten articles published within the past 5 years in the same domain, aiming to discern potential shifts in trends and methodological quality. Web of Science was used to search for articles on stroke rehabilitation. The data extracted from the articles included title, journal impact factor, year of publication, total number of citations, article topic, study design and others. The level of evidence and methodological quality were assessed by two reviewers. Non-invasive brain stimulation and robotic rehabilitation were frequently discussed in the top 50 articles. We found that there was no difference in methodology quality between the top 50 articles in all years and the top ten articles in the past 5 years. Furthermore, the number of citations and citation density were not associated with the methodological quality. The findings suggest that the number of citations alone may not be a reliable indicator of research quality.
Association of age and sex at onset with Glenohumeral Osteoarthritis: A systematic review and meta-analysis
Authors: Prakash Ravi , Gardner James E. , Petric Ursa B. , Pathak Rashmi , Atem Folefac , Jain Nitin B.
Published: January 2024

Objective

The aim of the present systematic review is to synthesize existing evidence (qualitative and quantitative) regarding age- and sex-specific differences with glenohumeral osteoarthritis (GH OA).

Design

The electronic databases PubMed, Medline and Web of Science were searched up to March 15, 2023. Articles reporting on the association of risk factors (age and sex) with GH OA were considered. We used Newcastle-Ottawa scale to assess study quality. Meta-analysis was conducted to quantitatively summarize the association of age and sex with GH OA.

Results

A total of 24 articles were retrieved for full-text review. Out of twenty-four articles, 8 articles reporting age-specific and 5 articles reporting sex-specific associations with GH OA were included. The odds ratio (OR) for the age [OR-3.18; 95% confidence interval (CI)-1.10-15.92] and female sex [OR-1.78; 95%CI-0.95-3.42] were increased and observed statistically significant.

Conclusions

The present systematic review and meta-analysis suggests the role of increasing age as one of the significant contributors to GH OA. However, association of female sex with GH OA is least convincing. Future studies are required to understand the molecular mechanisms behind the contributory role of increasing age and female sex in the establishment of GH OA.
Role of Outpatient Physical Medicine and Rehabilitation in a Multidisciplinary Prehabilitation Program for Older Adults Before Allogeneic Hematopoietic Stem Cell Transplant
Authors: Cheng Jessica T. , Obaisi Obada , Yadav Rajesh , Gupta Ekta , Fu Jack B. , Bruera Eduardo , Collaco Alisha , Szewczyk Nicholas , Popat Uday R. , Ngo-Huang An
Published: January 2024

Introduction

Physical rehabilitation is increasingly incorporated throughout the allogeneic hematopoietic stem cell transplant journey for older adults.

Objective

This study aimed to describe physical medicine and rehabilitation–related diagnoses, exercise barriers, and management recommendations for older adults before allogeneic hematopoietic stem cell transplant.

Design

Fifty physical medicine and rehabilitation consults as part of the Enhanced Recovery-Stem Cell Transplant multidisciplinary prehabilitation program at a comprehensive cancer center were retrospectively reviewed.

Results

Many physical medicine and rehabilitation–related diagnoses (173), exercise barriers (55), and management recommendations (112) were found. Common diagnoses were musculoskeletal dysfunction (more commonly back, shoulder, then knee) (n = 39, 23%) and fatigue (n = 36, 21%). Common exercise barriers were also musculoskeletal dysfunction (more commonly back, knee, then shoulder) (total n = 20, 36%) and fatigue (n = 20, 36%). Most patients (n = 32, 64%) had one or more exercise barriers. Common physical medicine and rehabilitation management recommendations were personalized exercise counseling (n = 37, 33%), personalized nutrition management (n = 19, 17%), body composition recommendations (n = 17, 15%), medications (n = 15, 13%), and orthotics and durable medical equipment (n = 8, 7%).

Conclusions

Routine physical medicine and rehabilitation referral of older allogeneic hematopoietic stem cell transplant patients for prehabilitation resulted in the identification of many rehabilitative needs and substantial additional management recommendations. Increased early, collaborative prehabilitation efforts between physical medicine and rehabilitation and allogeneic hematopoietic stem cell transplant teams to optimize care for these patients is recommended.
Age-Related Trajectory and Age at Peak Competitive Performance in Wheelchair Rugby Players at the Paralympic Games
Authors: Gomes Costa Rodrigo Rodrigues , Ribeiro Neto Frederico , Ramos Beatriz Lucena , Tanhoffer Ricardo , O’Shea Bob , Winckler Ciro
Published: January 2024

Objective

The first objective is to examine the age-related trajectory of competitive performance and the age at peak competitive performance in wheelchair rugby players at the Paralympic Games. Another objective is to verify age correlations with performance over the years for each class.

Design

This is a retrospective cohort study.

Results

Data were collected from the official results books of the Paralympic games. The mean age (SD) of the 267 players and 448 analyzed data from all Paralympic games (from Sidney 2004 to Tokyo 2020) across all classes was 32.8 (6.4) yrs, and the age at peak competitive performance was 30.6 (7.4) yrs. Each class had no statistical difference in age at peak competitive performance. In addition, there was no significant correlation between age and performance within classes or across all Paralympic games.

Conclusions

The findings indicate that wheelchair rugby players’ age at peak competitive performance is 30.6 yrs, which remains consistent across all classes. There is no statistical correlation between age and performance in wheelchair rugby. These findings significantly affect effective talent identification and athlete development programs. This impact ensures that athletes receive the necessary support to reach their maximum potential while avoiding the pitfalls of underestimating or overestimating their stages of development.
Performance of the 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease in a Latin American Cohort
Authors: Martín-Nares Eduardo , Hernández-Molina Gabriela , Baenas Diego Federico , Delgado de la Mora Jesús , Caeiro Francisco , Wurmann Kiblisky Pamela , Pimentel-Quiroz Victor R. , Ascuña Valdivia Valery , Faz-Munoz David , Saad Emanuel José , Cairoli Ernesto , Elgueta Pinochet Sergio , Madariaga Charaja Hugo , Montante-Montes de Oca Daniel , Gallo Jesica Romina , Ugarte-Gil Manuel F. , Neira Oscar , Burgos Paula I. , Paira Sergio ,   Grupo Latino Americano de Estudio de la Enfermedad Relacionada a IgG4 (GLAER-IgG4)
Published: January 2024

Background/Objective

The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria (2019 AECC) for IgG4-related disease (IgG4-RD) is considered a significant advancement in the study of this condition. Most studies evaluating their performance have focused on White and Asian patients, leaving a knowledge gap regarding Latin American populations. Therefore, this study aimed to assess the performance of the 2019 AECC for IgG4-RD in a cohort of Latin American patients.

Methods

A multicenter medical records review study was conducted, involving centers from Argentina, Chile, Mexico, Peru, and Uruguay. Data on IgG4-RD patients and mimicker conditions were collected through a standardized online form. The criterion standard for diagnosing IgG4-RD was based on the fulfillment of the Comprehensive Diagnostic Criteria for IgG4-RD and/or the Consensus Statement on Pathology. The 2019 AECC was retrospectively applied.

Results

We included 300 patients, with 180 (60%) having IgG4-RD and 120 (40%) having mimicker conditions. The 2019 AECC had a sensitivity of 66.7% and a specificity of 100%. Sensitivity increased to 73.3% when disease-specific autoantibody items were removed, without affecting specificity. The true-positive cases had more involved organs, a higher availability of biopsy results, and were more likely to belong to the Mikulicz/systemic and proliferative phenotypes.

Conclusions

The use of the 2019 AECC for IgG4-RD in a Latin American population confirms its high specificity in excluding those without the disease. The presence of concomitant autoimmune diseases and clinically nonsignificant disease-specific autoantibodies excludes a significant number of patients from fulfilling the criteria.
Rim4 is a Thermal Sensor and Driver of Meiosis-specific Stress Granules
Authors: Zhang Rudian , Li Shunjin , Feng Wenzhi , Qian Suhong , Chellappa Akshay John , Wang Fei
Published: January 2024

Rim4 is a meiosis-specific RNA-binding protein (RBP) that sequesters mRNAs to suppress their translation. Previous work has defined the Rim4 C-terminal low-complexity domain (LCD) as sequences that form self-propagating amyloid-like aggregates. Here, we uncovered a dynamic and reversible form of Rim4 self-assembly primarily triggered by heat during meiosis, proportionally from 30°C to 42°C. The formed thermal Rim4 condensates in cell promptly stimulates stress granule (SG) assembly, recruiting SG-resident proteins, such as Pab1 and Pbp1, and strikingly, decreases the required temperature for meiotic SG formation (∼33°C) by ∼9°C as compared to mitosis (∼42°C). This sensitization of meiotic SG formation to heat effectively prevents meiosis progression and sporulation under harmful thermal turbulence. Meanwhile, the Rim4-positive meiotic SGs protect Rim4 and Rim4-sequestered mRNAs from autophagy to allow a rapid recovery from stalled meiosis upon the stress relief. Mechanistically, we found that the yeast 14-3-3 proteins (Bmh1 and Bmh2) and nucleic acids brake initiation of heat-induced Rim4 self-assembly, and Hsp104 facilitates the restoration of intracellular Rim4 distribution during the recovery.
Topographic variation in neurotransmitter receptor densities explains differences in intracranial EEG spectra
Authors: Stoof U.M. , Friston K.J. , Tisdall M. , Cooray G.K. , Rosch R.E.
Published: January 2024

Neurotransmitter receptor expression and neuronal population dynamics show regional variability across the human cortex. However, currently there is an explanatory gap regarding how cortical microarchitecture and mesoscopic electrophysiological signals are mechanistically related, limiting our ability to exploit these measures of brain (dys)function for improved treatments of brain disorder; e.g., epilepsy.

To bridge this gap, we leveraged dynamic causal modelling (DCM) and fitted biophysically informed neural mass models to a normative set of intracranial EEG data. Subsequently, using a hierarchical Bayesian modelling approach, we evaluated whether model evidence improved when information about regional neurotransmitter receptor densities is provided. We then tested whether the inferred constraints — furnished by receptor density — generalise across different electrophysiological recording modalities.

The neural mass models explained regionally specific intracranial EEG spectra accurately, when fitted independently. Incorporating prior information on receptor distributions, further improved model evidence, indicating that variability in receptor density explains some variance in cortical population dynamics. The output of this modelling provides a cortical atlas of neurobiologically informed intracortical synaptic connectivity parameters that can be used as empirical priors in future — e.g., patient specific — modelling, as demonstrated in a worked example (a single-subject mismatch negativity study).

In summary, we show that molecular cortical characteristics (i.e., receptor densities) can be incorporated to improve generative, biophysically plausible models of coupled neuronal populations. This work can help to explain regional variations in human electrophysiology, may provide a methodological foundation to integrate multi-modal data, and might serve as a normative resource for future DCM studies of electrophysiology.

Significance Statement

Understanding the link between measures of brain function and their underlying molecular and synaptic constraints is essential for developing and validating personalised, pharmacological interventions. But despite increasing availability of detailed normative datasets of human brain structure and function — across modalities and spatial scales — translating between these remains challenging.

Using two large normative datasets — intracranial EEG recordings and autoradiographic receptor density distributions — we demonstrate that generative models of these data can link structure to function. Specifically, we show that regional oscillatory neuronal population activity is shaped by the distribution of neurotransmitter receptors. This modelling furnishes an atlas of normative parameter values, which can provide neurobiologically informed priors for in-silico (e.g., Digital Twin) characterisation of normal and disordered brain functioning.
The antagonistic transcription factors, EspM and EspN, regulate the ESX-1 secretion system inM. marinum
Authors: Nicholson Kathleen R. , Cronin Rachel M. , Prest Rebecca J. , Menon Aruna R. , Yang Yuwei , Jennisch Madeleine K. , Champion Matthew M. , Tobin David M. , Champion Patricia A.
Published: January 2024

Bacterial pathogens use protein secretion systems to transport virulence factors and regulate gene expression. Among pathogenic mycobacteria, includingMycobacterium tuberculosisandMycobacterium marinum,ESX-1 (ESAT-6 system 1) secretion is crucial for host interaction. Secretion of protein substrates by the ESX-1 secretion system disrupts phagosomes, allowing mycobacteria cytoplasmic access during macrophage infections. Deletion or mutation of the ESX-1 system attenuates mycobacterial pathogens. Pathogenic mycobacteria respond to the presence or absence of the ESX-1 system in the cytoplasmic membrane by altering transcription. Under laboratory conditions, the EspM repressor and WhiB6 activator control transcription of specific ESX-1-responsive genes, including the ESX-1 substrate genes. However, deleting theespMorwhiB6genes does not phenocopy the deletion of the ESX-1 substrate genes during macrophage infection byM. marinum. In this study, we identified EspN, a critical transcription factor whose activity is masked by the EspM repressor under laboratory conditions. In the absence of EspM, EspN activates transcription ofwhiB6and ESX-1 genes both during laboratory growth and during macrophage infection. EspN is also independently required forM. marinumgrowth within and cytolysis of macrophages, similar to the ESX-1 genes, and for disease burden in a zebrafish larval model of infection. These findings suggest that EspN and EspM coordinate to counterbalance the regulation of the ESX-1 system and support mycobacterial pathogenesis.

Importance

Pathogenic mycobacteria, which are responsible for tuberculosis and other long-term diseases, use the ESX-1 system to transport proteins that control the host response to infection and promote bacterial survival. In this study, we identify an undescribed transcription factor that controls the expression of ESX-1 genes and is required for both macrophage and animal infection. However, this transcription factor is not the primary regulator of ESX-1 genes under standard laboratory conditions. These findings identify a critical transcription factor that likely controls expression of a major virulence pathway during infection, but whose effect is not detectable with standard laboratory strains and growth conditions.
Mutations in yeast are deleterious on average regardless of the degree of adaptation to the testing environment
Authors: Bao Kevin , Strayer Brant R. , Braker Neil P. , Chan Alexandra A. , Sharp Nathaniel P.
Published: January 2024

The role of spontaneous mutations in evolution depends on the distribution of their effects on fitness. Despite a general consensus that new mutations are deleterious on average, a handful of mutation accumulation experiments in diverse organisms instead suggest that of beneficial and deleterious mutations can have comparable fitness impacts, i.e., the product of their respective rates and effects can be roughly equal. We currently lack a general framework for predicting when such a pattern will occur. One idea is that beneficial mutations will be more evident in genotypes that are not well adapted to the testing environment. We tested this prediction experimentally in the laboratory yeastSaccharomyces cerevisiaeby allowing nine replicate populations to adapt to novel environments with complex sets of stressors. After >1000 asexual generations interspersed with 41 rounds of sexual reproduction, we assessed the mean effect of induced mutations on yeast growth in both the environment to which they had been adapting and the alternative novel environment. The mutations were deleterious on average, with the severity depending on the testing environment. However, we find no evidence that the adaptive match between genotype and environment is predictive of mutational fitness effects.
Functionality of arousal-regulating brain circuitry at rest predicts human cognitive abilities
Authors: Podvalny Ella , Sanchez-Romero Ruben , Cole Michael W
Published: January 2024

Arousal state is regulated by subcortical neuromodulatory nuclei, such as locus coeruleus, which send wide-reaching projections to cortex. Whether higher-order cortical regions have the capacity to recruit neuromodulatory systems to aid cognition is unclear. Here, we hypothesized that select cortical regions activate the arousal system, which in turn modulates large-scale brain activity, creating a functional circuit predicting cognitive ability. We utilized the Human Connectome Project 7T functional magnetic resonance imaging dataset (N=149), acquired at rest with simultaneous eye tracking, along with extensive cognitive assessment for each subject. First, we discovered select frontoparietal cortical regions that drive large-scale spontaneous brain activity specifically via engaging the arousal system. Second, we show that the functionality of the arousal circuit driven by bilateral posterior cingulate cortex (associated with the default mode network) predicts subjects cognitive abilities. This suggests that a cortical region that is typically associated with self-referential processing supports cognition by regulating the arousal system.
The landscape of paediatric infectious disease exposure in a rural sub-Saharan Africa setting in Kilifi, Kenya: longitudinal serological analysis over two decades and priorities for future vaccine development
Authors: Foley Deirdre F , Chege Timothy K , Kabagenyi Joyce , McCarthy Karen , Gicheru Elijah T , Kibinge Nelson , Maina Angela W , Waeni Jacqueline M , Clemens Ralf , Clemens Sue-Ann Costa , Tuju James , Sande Charles J
Published: January 2024

Background

The paucity of data on the contemporary causes of serious infection among the world’s most vulnerable children means the landscape of emerging paediatric infectious disease remains largely undefined and out of focus on the global vaccine research and development agenda.

Methods

We aimed to partially define the paediatric infectious disease landscape in a typical low-income setting in sub-Saharan Africa in Kilifi, Kenya by simultaneously estimating antibody prevalence for 38 infectious diseases using a longitudinal birth cohort that was sampled between 2002 and 2008 and a paediatric inpatient cohort that was sampled between 2006 and 2017.

Findings

Among the infectious diseases with the highest antibody prevalence in the first year of life were vaccine-preventable diseases such as RSV (57.4%), mumps (31.5%) and influenza H3N2 (37.3%). Antibody prevalence forPlasmodium falciparumshifted substantially over time, from 47% in the mid 2000s to 13% approximately 10 years later corresponding to a documented decline in parasite transmission. A high prevalence of antibodies was also observed in the first year of life for infections for which no licenced vaccines are currently available, including norovirus (34.2%), cytomegalovirus (44.7%), EBV (29.3%) and coxsackie B virus (40.7%). The prevalence to antibodies to vaccine antigens in the local immunisation schedule was generally high but varied by antigen.

Interpretation

The data show a high and temporally stable infection burden of RSV, mumps and influenza, providing a compelling evidence base to support progress towards the introduction of these vaccines into the local immunization schedule. The high prevalence of norovirus, EBV, CMV and Coxsackie B provide rationale for increased vaccine research and development investment.

Funding

This research was funded by the Wellcome Trust (grant no. WT105882MA).
The contribution of animal antibiotic use to antibiotic resistance in humans: Panel evidence from Denmark
Authors: Emes Eve , Belay Dagim , Knight Gwenan M
Published: January 2024

Antibiotic use (ABU) in animals is postulated to be a major contributor to selection of antibiotic resistance (ABR) which subsequently causes infections in human populations. However, there are few quantifications of the size of this association. Denmark, as a country with high levels of pig production and good surveillance data, is an ideal case study for exploring this association.

In this paper, we compile a dataset on ABU across several animal species and antibiotic classes, and data on the rate of antibiotic resistance (ABR) in humans across key pathogens, in Denmark over time (2010 - 2020). We run panel data regressions (fixed effects, random effects, first difference and pooled ordinary least squares) to test the association between the level of ABR in human infections and the level of ABU in animals.

Between ABR in humans and ABU in animal species, we find a positive relationship for cattle, some evidence of a positive relationship for poultry and companion animals, and a negative relationship for fish, although the latter is likely driven by confounding factors. When lagging ABU by one year, the effect of ABU in cattle and companion animals remained similar, the effect of ABU in poultry fell in size, and ABU in fish was no longer significant, perhaps due to differences in life cycle length among animal species. Additional covariates were explored, including pet populations, agricultural production and GDP per capita (at purchasing power parity), but these results were limited by the statistical power of the dataset. Under all models, animal ABU determined only a minority of the change in human ABR levels in this context with adjusted R2 ranging from 0.19 to 0.44.

This paper supports the role of animal ABU in determining human ABR levels but suggests that, despite comprising a large portion of systemwide ABU, it only explains a minority of the variation. This is likely driven in part by data limitations, and could also be due to a persistence of ABR once resistance has emerged, suggesting a significant role for socioeconomic and transmission factors in bringing ABR down to desirable levels.

Highlights

- We use panel regression to explore the link between animal ABU and human ABR in Denmark

- ABU was linked to ABR in cattle, and potentially in poultry and companion animals

- However, animal ABU did not appear to be the main determinant of human ABR

- This could be due to poor data, or persistence of ABR after reaching a certain level

- Animal ABU reductions alone may be insufficient to curb ABR