bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of human expert visual inspection on the discovery of strong gravitational lenses
Authors: Rojas Karina , Collett Thomas E , Ballard Daniel , Magee Mark R , Birrer Simon , Buckley-Geer Elizabeth , Chan James H H , Clément Benjamin , Diego José M , Gentile Fabrizio , González Jimena , Joseph Rémy , Mastache Jorge , Schuldt Stefan , Tortora Crescenzo , Verdugo Tomás , Verma Aprajita , Daylan Tansu , Millon Martin , Jackson Neal , Dye Simon , Melo Alejandra , Mahler Guillaume , Ogando Ricardo L C , Courbin Frédéric , Fritz Alexander , Herle Aniruddh , Acevedo Barroso Javier A , Cañameras Raoul , Cornen Claude , Dhanasingham Birendra , Glazebrook Karl , Martinez Michael N , Ryczanowski Dan , Savary Elodie , Góis-Silva Filipe , Arturo Ureña-López L , Wiesner Matthew P , Wilde Joshua , Valim Calçada Gabriel , Cabanac Rémi , Pan Yue , Sierra Isaac , Despali Giulia , Cavalcante-Gomes Micaele V , Macmillan Christine , Maresca Jacob , Grudskaia Aleksandra , O’Donnell Jackson H , Paic Eric , Niemiec Anna , de la Bella Lucia F , Bromley Jane , Williams Devon M , More Anupreeta , Levine. Benjamin C
Published: June 2023

We investigate the ability of human ‘expert’ classifiers to identify strong gravitational lens candidates in Dark Energy Survey like imaging. We recruited a total of 55 people that completed more than 25 per cent of the project. During the classification task, we present to the participants 1489 images. The sample contains a variety of data including lens simulations, real lenses, non-lens examples, and unlabelled data. We find that experts are extremely good at finding bright, well-resolved Einstein rings, while arcs with g-band signal to noise less than ∼25 or Einstein radii less than ∼1.2 times the seeing are rarely recovered. Very few non-lenses are scored highly. There is substantial variation in the performance of individual classifiers, but they do not appear to depend on the classifier’s experience, confidence or academic position. These variations can be mitigated with a team of 6 or more independent classifiers. Our results give confidence that humans are a reliable pruning step for lens candidates, providing pure and quantifiably complete samples for follow-up studies.
Diagnostic criteria of chronic conjunctivitis: atopic keratoconjunctivitis and vernal keratoconjunctivitis
Authors: Leonardi Andrea , Righetti Giuseppe , Giovannini Giulia , De Marchi Vittorio , Occhiuto Matteo
Published: June 2023

Purpose of review

Chronic ocular allergies, vernal (VKC) and atopic keratoconjunctivitis (AKC) are relatively rare conditions that require definite diagnostic criteria to the most appropriate therapeutical approach.

Recent findings

The diagnosis of both VKC and AKC is generally based on clinical history, signs and symptoms, and the results of allergic tests, which allow to identify the different diseases phenotypes. However, other subtypes of the two diseases and/or overlaps may occur making the diagnosis non always so clear, such as VKC and AKC overlaps or adult-like VKC disease. Each of these phenotypes may be sustained by different mechanisms which are still not well defined but not only related to a type 2 inflammation. The further challenges will be to correlate clinical or molecular biomarkers to a single subtype or disease severity.

Definite criteria of chronic allergies will further guide to more specific therapeutical approaches.
Deep Learning Model for Automated Trainee Assessment During High-Fidelity Simulation
Authors: Siddiqui Asad , Zhao Zhoujie , Pan Chuer , Rudzicz Frank , Everett Tobias
Published: June 2023

Problem

Implementation of competency-based medical education has necessitated more frequent trainee assessments. Use of simulation as an assessment tool is limited by access to trained examiners, cost, and concerns with interrater reliability. Developing an automated tool for pass/fail assessment of trainees in simulation could improve accessibility and quality assurance of assessments. This study aimed to develop an automated assessment model using deep learning techniques to assess performance of anesthesiology trainees in a simulated critical event.

Approach

The authors retrospectively analyzed anaphylaxis simulation videos to train and validate a deep learning model. They used an anaphylactic shock simulation video database from an established simulation curriculum, integrating a convenience sample of 52 usable videos. The core part of the model, developed between July 2019 and July 2020, is a bidirectional transformer encoder.

Outcomes

The main outcome was the F1 score, accuracy, recall, and precision of the automated assessment model in analyzing pass/fail of trainees in simulation videos. Five models were developed and evaluated. The strongest model was model 1 with an accuracy of 71% and an F1 score of 0.68.

Next Steps

The authors demonstrated the feasibility of developing a deep learning model from a simulation database that can be used for automated assessment of medical trainees in a simulated anaphylaxis scenario. The important next steps are to (1) integrate a larger simulation dataset to improve the accuracy of the model; (2) assess the accuracy of the model on alternative anaphylaxis simulations, additional medical disciplines, and alternative medical education evaluation modalities; and (3) gather feedback from education leadership and clinician educators surrounding the perceived strengths and weaknesses of deep learning models for simulation assessment. Overall, this novel approach for performance prediction has broad implications in medical education and assessment.
Employee Perceptions of an Established Health and Wellness Coaching Program to Improve Behavior
Authors: Torres Georgia , Mukoma Gudani , Neophytou Natalia , Gradidge Philippe Jean-Luc
Published: June 2023

Objective

There is limited evidence, particularly qualitative analysis, of health and wellness interventions within the South African workplace. The purpose of this study is to explore whether health and wellness coaching when offered as part of an employee wellness program has potential for developing lifestyle change in a South African workplace.

Methods

There were four, 45-minute focus group discussions, where employees discussed their experiences of the workplace health and wellness intervention program.

Results

Main categories identified from the coding of the transcripts were purpose of the health and wellness coaching program, as well as employees’ program experience and improvement to the program. Common barriers to engagement, positive and negative experiences, and suggested improvements were defined by the employees.

Conclusions

The study highlighted the need of understanding employee perceptions in the development and implementation of a workplace health and wellness program.
Steroid Phobia in Patients With Vulvar Lichen Sclerosus
Authors: Delpero Emily , Sriharan Abi , Selk Amanda
Published: June 2023

Objective

Steroid phobia in people with dermatologic conditions is associated with noncompliance with topical corticosteroids (TCS). Although it has not been studied in those with vulvar lichen sclerosus (vLS), first-line therapy is lifelong maintenance TCS, and noncompliance is associated with impaired quality of life, progression of architecture changes, and vulvar skin cancer. The authors aimed to measure steroid phobia in patients with vLS and determine their most valued sources of information to direct future interventions to address this phenomenon.

Methods

The authors adapted a preexisting, validated scale for steroid phobia (TOPICOP), which is a 12-item questionnaire that produces a score of 0 = no phobia and 100 = maximum phobia. The anonymous survey was distributed across social media platforms with an in-person component at the authors’ institution. Eligible participants included those with clinical or biopsy-proven LS. Participants were excluded if they did not consent or did not communicate in English.

Results

The authors obtained 865 online responses over a 1-week period. The in-person pilot obtained 31 responses, with a response rate of 79.5%. Mean global steroid phobia score was 43.02 (21.9)% and in-person responses were not significantly different (40.94 [16.03]%, p = .59). Approximately 40% endorsed waiting as long as they can before using TCS and stop as soon as possible. The most influential sources to improve patient comfort with TCS were physician and pharmacist reassurance over online resources.

Conclusions

Steroid phobia is common in patients with vLS. Focused efforts to address steroid phobia among health care providers is the next best step toward improving patient comfort with TCS.
Recurrent High-Grade Squamous Intraepithelial Lesion After Loop Excision Procedure Versus Loop Procedure With Top Hat
Authors: Francoeur Alex A. , Furey Katelyn B. , Ramirez Juan , Klomhaus Alexandra M. , Holschneider Christine , Garcia Lisa M.
Published: June 2023

Objective

To evaluate single-pass loop electrosurgical excision procedure (LEEP-SP) versus LEEP with top hat (LEEP-TH) in terms of treatment failure defined as high-grade squamous intraepithelial lesion (HSIL) cytology within 2 years’ follow-up.

Methods

This single-institution cohort study used a prospectively collected cervical dysplasia database including all patients who underwent LEEP-SP or LEEP-TH for biopsy-proven cervical intraepithelial neoplasia between 2005 and 2019.

Results

Of 340 patients included, 178 underwent LEEP-SP and 162 LEEP-TH. The LEEP-TH patients were more likely to be older (mean age, 40.4 vs 36.5 years; p < .001) and have a positive preprocedure endocervical sampling (68.5% vs 11.8%; p < .001). Positive margins were found in 23 LEEP-SP (12.9%) and in 25 LEEP-TH (15.4%; p = .507). There was no significant difference in depth of excision between LEEP-SP (13.21 ± 23.19 mm) and LEEP-TH (17.37 ± 28.26 mm; p = .138). At 2 years, there was no difference in the rates of HSIL cytology (5.2% vs 6.3%; p = .698), any positive human papillomavirus test, or HSIL cytology (25% vs 15%; p = .284). The 57 patients undergoing repeat excision were more likely to be older (mean age, 40.95 vs 37.52 years; p = .023), have had a LEEP-TH (26.3% vs 73.7%; p < .001), and have initial cytologic HSIL (64.9% vs 35.0%; p < .001).

Conclusions

In this single-institution study, there is no difference in the rate of recurrent HSIL in patients undergoing LEEP-SP versus LEEP-TH. A LEEP-TH may have limited additional benefit over a LEEP-SP in the treatment of cervical HSIL.
Nondigestible Carbohydrate Consumption
Authors: Mysonhimer Annemarie R. , Holscher Hannah D.
Published: June 2023

Nondigestible carbohydrates (NDCs) are food components, including nonstarch polysaccharides and resistant starches. Many NDCs are classified as dietary fibers by the Food and Drug Administration. Because of their beneficial effects on human health and product development, NDCs are widely used in the food supply. However, although there are intake recommendations for total dietary fiber, recommendations for individual NDCs have yet to be established. Thus, this article provides guidance for nutrition and healthcare practitioners on NDC tolerable intake levels established from a recent synthesis of human trials. This knowledge can inform therapeutic doses and help to address the fiber gap.
Neck Hemorrhage
Authors: Bingham-Abujasen Kaileigh , Schmitt Jessicia , Knight Laura
Published: June 2023

Distinguishing artifactual postmortem hypostatic hemorrhages from injury is key to accurately diagnosing strangulation. Despite being a well-known phenomenon, the literature is limited. This retrospective case-control analysis characterizes anterior neck musculature hemorrhage patterns associated with postmortem artifact versus strangulation by comparing incidental neck hemorrhages noted on 20 autopsy reports from 2020 to 2021 to 10 strangulation controls from 2015 to 2021 in Northern Nevada. Cases were analyzed for body position and location/severity of musculature involvement. For artifact cases, 50.0% were prone, 40.0% supine, and 10.0% side-lying. A total of 55.6% of artifact cases and controls demonstrated neck hemorrhage laterality. A total of 80.0% of the prone cases versus 77.8% of supine had diffuse hemorrhage versus focal. A total of 63.2% of artifact cases involved the sternocleidomastoid versus 70.0% controls (P = 1.000), 26.3% involved soft tissues versus 20.0% (P = 1.000), 9.1% the sternohyoid versus 40.0% (P = 0.149), 27.3% the sternothyroid versus 60.0% (P = 0.198), 9.1% the thyrohyoid versus 10.0% (P = 1.000), 18.2% the omohyoid versus 30.0% (P = 0.635), and 10.0% the tongue versus 50.0% (P = 0.026). Despite the limitations, this study demonstrated that while prone positioning is a contributing factor to the development of anterior neck hemorrhages, there are other factors than postmortem hypostasis.
Clinicopathologic Features and Immune Cell Subtypes Analysis of Tumor-infiltrating Lymphocytes Rich Invasive Breast Carcinoma of No Special Type
Authors: Zhao Yan , Huang Ting , Jin Xin , Gong Xiao-meng , Lu Yuan-zhi
Published: June 2023

Tumor-infiltrating lymphocytes (TILs) rich invasive breast carcinoma no special type (IBC-NST) is an updated name introduced in the fifth edition WHO classification of breast tumors. Typical medullary breast carcinoma (MBC) represents one end of the spectrum of TILs-rich IBC-NST rather than a distinct morphologic subtype in the new category. A total of 42 cases of MBC and 180 cases of high-grade triple-negative breast cancer (TNBC) without medullary features were included. All samples were stained for CD20, CD4, CD8, and FoxP3 by immunohistochemistry staining. TILs infiltration was more prominent in the MBC tumor nests and in the stroma of high-grade TNBC without medullary features. The average stromal TILs percentage was 78.10% and 61.33%. MBC showed significantly lower numbers of lymphocytes expressing FoxP3 (P < 0.001), no significant difference in the number of CD4 (P = 0.154), CD8 (P = 0.199), and a significantly higher CD8/FoxP3 ratio (P < 0.001) than the other high-grade TNBC. MBC cases demonstrated less aggressive features such as lower TNM stage (P = 0.031), smaller tumor size (P = 0.010), and negative lymph node status (P = 0.021) than the other high-grade TNBC. The 5-year disease-free survival and overall survival were significantly higher for MBC 82.50% and 85.00% compared with the other high-grade TNBC(54.49% and 58.68%). MBC is mostly triple-negative with higher nuclear atypia. Despite advanced staging based on cell morphology, it has low malignancy and a good prognosis. Differences in biological features and prognosis between MBC and high-grade TNBC without medullary features may be associated with the composition and function of TILs. Immune cell subtypes are complex in TILs-rich IBC-NST and deserve further investigation.
The Histologic and Molecular Spectrum of Highly Differentiated HPV-independent Cervical Intraepithelial Neoplasia
Authors: Regauer Sigrid , Reich Olaf
Published: June 2023

Recently, the World Health Organization (WHO) recognized the existence of human papillomavirus (HPV)-independent invasive cervical squamous cell carcinoma (SCC), but HPV-independent precursor lesions were not included due to the lack of description of this rare entity. We present the histologic spectrum of highly differentiated squamous HPV-negative and p16ink4a-negative precursor lesions adjacent to and/or preceding invasive HPV-negative cervical SCC in 3 patients. The histologic features resembled those described for vulvar HPV-negative precursor lesions. One precursor featured a proliferation of atypical basal keratinocytes with mitotic activity, premature squamatization in elongated epithelial rete, and mostly regular superficial squamous differentiation with TP53 mutation and immunohistochemical p53 overexpression termed differentiated cervical intraepithelial neoplasia (d-CIN). The other 2 precursors included verruciform acanthosis with plump rete, minimal atypia, and an EGFR mutation that resembled vulvar acanthosis with altered differentiation, and an exophytic papillary proliferation with a PIK3CA mutation resembling the differentiated exophytic vulvar intraepithelial lesion. Two precursors that preceded the invasive SCC harbored an additional pathogenic SMARCB1 mutation. The cytologic smears of d-CIN revealed 3-dimensional branched basaloid tubular structures and eosinophilic squamous cell clusters mimicking the histologic features. In conclusion, highly differentiated cervical HPV-negative precursors are characteristic intraepithelial squamous lesions with somatic mutations that resemble those described in vulvar HPV-independent carcinogenesis. For optimal reproducibility, we propose a simplistic classification of these HPV-negative cervical precursors in TP53-mutated d-CIN and p53 wild-type verruciform intraepithelial neoplasia.
Tampa Scale of Kinesiophobia may underestimate task-specific fear of movement in people with and without low back pain
Authors: Tissot Liam-Pierre Mathieu , Evans David William , Kirby Edward , Liew Bernard Xian Wei
Published: June 2023

Introduction:

The Tampa Scale of Kinesiophobia (TSK) is commonly used to assess fear of movement (FoM) in people with low back pain (LBP). However, the TSK does not provide a task-specific measure of FoM, whereas image-based or video-based methods may do so.

Objectives:

To compare the magnitude of FoM when assessed using 3 methods (TSK-11, image of lifting, video of lifting) in 3 groups of people: current LBP (LBP), recovered LBP (rLBP), and asymptomatic controls (control).

Methods:

Fifty-one participants completed the TSK-11 and rated their FoM when viewing images and videos depicting people lifting objects. Low back pain and rLBP participants also completed the Oswestry Disability Index (ODI). Linear mixed models were used to estimate the effects of methods (TSK-11, image, video) and group (control, LBP, rLBP). Linear regression models were used to assess associations between the methods on ODI after adjusting for group. Finally, a linear mixed model was used to understand the effects of method (image, video) and load (light, heavy) on fear.

Results:

In all groups, viewing images (P = 0.009) and videos (P = 0.038) elicited greater FoM than that captured by the TSK-11. Only the TSK-11 was significantly associated with the ODI (P < 0.001). Finally, there was a significant main effect of load on fear (P < 0.001).

Conclusion:

Fear of specific movements (eg, lifting) may be better measured using task-specific measures, such as images and videos, than by task-generic questionnaires, such as the TSK-11. Being more strongly associated with the ODI, the TSK-11 still plays an important role in understanding the impact of FoM on disability.
Applied Anatomy of the Lower Eyelids’ Preseptal Space for Treating Ectropion and Retraction with Soft Tissue Fillers
Authors: Hartstein Morris E. , Gildener-Leapman Juliana , Bernardini Francesco P. , Cassuto Daniel , Wulc Allan E. , Ni Garrett , Alfertshofer Michael G. , Cotofana Sebastian
Published: June 2023

Background:

Lower eyelid malposition can result from age-related changes such as ectropion or post-surgical changes like retraction following lower lid blepharoplasty. The current accepted treatment is surgical, but previously it was indicated that soft tissue fillers can be used as well with good outcome. However, the underlying anatomy is incompletely described when guiding practitioners toward minimally invasive injections of the lower eyelid.

Objective:

To describe a minimally invasive injection technique adjusted to the complex anatomy of the lower eyelid for the treatment of ectropion and retraction of the lower eyelid.

Methods:

A total of n = 39 periorbital regions of n = 31 study participants were retrospectively analyzed using photographs prior and post to reconstruction of the lower eyelid with soft-tissue fillers. Two independent raters assessed the degree of ectropion and lower eyelid retraction (DELER; 0 - 4, best-to-worst) before and after the reconstruction and the overall aesthetic improvement using the Periorbital Aesthetic Improvement Scale (PAIS).

Results:

The median DELER score improved statistically significantly from 3.00 (1.5) to 1.00 (1.0) with p <0.001. The mean volume of soft tissue filler material applied per eyelid was 0.73 cc (0.5). The median PAIS following the treatment was rated as 4.00 (0.5) indicating improvement of the periorbital functional and aesthetic appearance.

Conclusion:

Anatomic knowledge of the lower eyelid and of the preseptal space is of clinical relevance when trying to reconstruct the lower eyelid with soft-tissue fillers. The targeted space provides optimal lifting capacities for improved aesthetic and functional outcome.
Role of turgor-pressure induced boundary tension in the maintenance of the shoot apical meristem of
Arabidopsis thaliana
Authors: Michael Christian , Banwarth-Kuhn Mikahl , Rodriguez Kevin , Ta Calvin-Khang , Roy-Chowdhury Amit , Chen Weitao , Venugopala Reddy G. , Alber Mark
Published: June 2023

In plants, the robust maintenance of tissue structure is crucial to supporting its functionality. The multi-layered shoot apical meristem (SAM) of
Arabidopsis,
containing stem cells
,
is an approximately radially symmetric tissue whose shape and structure is maintained throughout the life of the plant. In this paper, a new biologically calibrated pseudo-three-dimensional (P3D) computational model of a longitudinal section of the SAM is developed. It includes anisotropic expansion and division of cells out of the cross-section plane, as well as representation of tension experienced by the SAM epidermis. Results from the experimentally calibrated P3D model provide new insights into maintenance of the structure of the SAM epidermal cell monolayer under tension and quantify dependence of epidermal and subepidermal cell anisotropy on the amount of tension. Moreover, the model simulations revealed that out-of-plane cell growth is important in offsetting cell crowding and regulating mechanical stresses experienced by tunica cells. Predictive model simulations show that tension-determined cell division plane orientation in the apical corpus may be regulating cell and tissue shape distributions needed for maintaining structure of the wild-type SAM. This suggests that cells' responses to local mechanical cues may serve as a mechanism to regulate cell- and tissue-scale patterning.
Bacterium of one thousand and one variants: genetic diversity of Neisseria gonorrhoeae pathogenicity.
Authors: Kurzyp Kacper , Harrison Odile B.
Published: June 2023

The bacterium

Neisseria gonorrhoeae

causes the sexually transmitted infection gonorrhoea. Although diverse clinical manifestations are associated with gonorrhoea, ranging from asymptomatic through to localized and disseminated infection, very little is known about the bacterial determinants implicated in causing such different clinical symptoms. In particular, virulence factors, although defined and investigated in particular strains, often lack comprehensive analysis of their genetic diversity and how this relates to particular disease states. This review examines the clinical manifestations of gonorrhoea and discusses them in relation to disease severity and association with expression of particular virulence factors including PorB, lipooligosaccharide (LOS) and Opa, both in terms of their mechanisms of action and inter- and intra-strain variation. Particular attention is paid to phase variation as a key mechanism of genetic variation in the gonococcus and the impact of this during infection. We describe how whole-genome-sequence-based approaches that focus on virulence factors can be employed for vaccine development and discuss whether whole-genome-sequence data can be used to predict the severity of gonococcal infection.
Identification of Therapeutic Leads fromFicus hispidaFruit Phytochemicals against Prostate Cancer Using Pharmacoinformatic and Molecular Dynamics Simulation Approach
Authors: Rahman MD. Hasanur , Rahman Md. Ataur , Zahan Md. Sarwar , Biswas Partha , Islam Silme , Reshad Riyan Al Islam , Sohag Abdullah Al Mamun , Gupta Bablu , Islam Redwanul , Hannan Md. Abdul , Kim Woojin , Moon Seungjoon , Uddin Md Jamal , Kim Bonglee
Published: June 2023

Prostate cancer is one of the leading causes of death and the most common cancer type in men. In this study, potential leads from the phytochemicals ofFicus hispidafruit were screened using in silico tools against androgen receptor (AR), a known target for prostate cancer. PASS online and ADMET tools were used to screen specific phytochemicals that are relevant to prostate cancer treatment and have drug-like properties. Of 13, a total of 10 phytochemicals passed PASS online and ADMET screening. Next, a total of three phytochemicals, including nodakenetin (CID: 26305), isowigtheone hydrate (CID: 66728267), and 7-hydroxycoumarin (CID: 5281426) were selected based on their docking scores (-9.946 to -7.653 kcal/mol) and relevance to selective bioactivity. The MD simulation further confirmed the binding stability of these three phytochemicals with their target AR protein and determined that the main amino acid residues mainly responsible for this stability including RMSD, RMSF, and post simulation binding free energies. These findings suggest that these three phytochemicals ofFicus hispidafruit can further be developed as prospective therapeutics against prostate cancer.
Activation of the TRIF pathway and downstream targets results in the development of precancerous lesions during infection withHelicobacter
Authors: Bali Prerna , Lozano-Pope Ivonne , Hernandez Jonathan , Estrada Monica V , Corr Maripat , Turner Michael A. , Bouvet Michael , Benner Christopher , Obonyo Marygorret
Published: June 2023

Helicobacter pylori(H. pylori)infection is an established cause of many digestive diseases, including gastritis, peptic ulcers, and gastric cancer. However, the mechanism by which infection withH. pyloricauses these disorders is still not clearly understood. This is due to insufficient knowledge of pathways that promoteH. pylori-induced disease progression. We have established aHelicobacter-induced accelerated disease progression mouse model, which involves infecting mice deficient in the myeloid differentiation primary response 88 gene (Myd88-/-) withH. felis. Using this model, we report here that that progression ofH. felis-induced inflammation to high-grade dysplasia was associated with activation of type I interferon (IFN-I) signaling pathway and upregulation of related downstream target genes, IFN-stimulated genes (ISGs). These observations were further corroborated by the enrichment of ISRE motifs in the promoters of upregulated genes. Further we showed thatH. felis-induced inflammation in mice deficient in Toll/interleukin-1 receptor (TIR)-domain-containing adaptor inducing interferon-β (TRIF,TrifLps2) did not progress to severe gastric pathology, indicating a role of the TRIF signaling pathway in disease pathogenesis and progression. Indeed, survival analysis in gastric biopsy samples from gastric cancer patients illustrated that high expression ofTrifwas significantly associated with poor survival in gastric cancer.
Upper limb functional recovery in chronic stroke patients after COVID-19-interrupted rehabilitation: An observational study
Authors: Sakamoto Daigo , Hamaguchi Toyohiro , Nakayama Yasuhide , Hada Takuya , Abo Masahiro
Published: June 2023

Background

Upper limb function of chronic stroke patients declined when outpatient rehabilitation was interrupted, and outings restricted, due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In this study, we investigated whether these patients recovered upper limb function after resumption of outpatient rehabilitation.

Methods

In this observational study, 43 chronic stroke hemiplegic patients with impaired upper extremity function were scored for limb function via Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), Action Research Arm Test (ARAT) after a structured interview, evaluation, and intervention. Scores at 6 months and 3 months before and 3 months after rehabilitation interruption were examined retrospectively, and scores immediately after resumption of care and at 3 and 6 months after resumption of care were examined prospectively. The amount of change for each time period and an analysis of covariance was performed with time as a factor and the change in FMA-UE and ARAT scores as dependent variables and by setting statistical significance at 5%.

Results

Time of evaluation significantly impacted total, part C, and part D of FMA-UE as well as total, pinch, and gross movement of ARAT. Post-hoc tests showed that the magnitude of change in limb function scores from immediately after resumption of rehabilitation to 3 months after resumption was significantly higher than the change from 3 months before to immediately after interruption for total, and part D of FMA-UE, and grip, and gross movement of ARAT (p<0.05).

Conclusions

The results suggest that upper limb functional decline in chronic stroke patients, caused by the SARS-CoV-2 pandemic-related therapy interruption and outing restrictions, was resolved after approximately 3 months of resumption of rehabilitation therapy. Our data can serve as reference standards for planning and evaluating treatment for chronic stroke patients with impaired upper limb function due to inactivity.
Evaluation of Mental Health and Quality of Life among Afghan Refugees in Iran
Authors: Saeidi Mahdieh , Sadr Saeed , Samimi Ardestani Seyed Mehdi , Nooraeen Sara
Published: June 2023

Background

Forced migration is significant in Middle Eastern countries. Afghanistan has a high rate of forced immigration due to decades of war and insecurity. This figure has risen, especially in the recent Taliban offensive. It is important to pay attention to the mental health of refugees and to evaluate the risk factors affecting the improvement of their mental health and quality of life. This study aims to investigate the mental health and quality of life among Afghan refugees living in Iran.

Methods

The study sample consisted of 200 Afghan refugees living in Tehran, Iran. Demographic characteristics, mental status and quality of life were investigated. One-sample t-test, chi-square, paired t-test, analysis of variance, and Scheffe post hoc test and logistic regression were used to analyze the data.

Results

Anxiety and insomnia were the most prevalent mental health symptoms among Afghan refugees. Depressive symptoms were higher in unemployed ones and women. Most of the participants (56.5%) had moderate quality of life and social relationship had the lowest score in quality-of-life domain.

Conclusions

The frequency of mental health disorders and low quality of life has been considerably high among Afghan Refugees in Iran. The mental health and quality of life of refugees should be further considered, especially after domestic wars and insecurities.
Volunteers of Third Sector Organizations in supporting older adults in the transition from hospital to home: A comparative case study
Authors: Nelson MLA , Singh H. , Saragosa M.
Published: June 2023

Introduction

With increasing attention to models of transitional support delivered through multisectoral approaches, third sector organizations have supported community reintegration and independent living post hospitalization. This study aimed to identify core elements of these programs, facilitators and barriers to service implementation, and to understand the perspectives of providers and recipients.

Methods and Analysis

A comparative case study was conducted, collecting data from two ‘Home from Hospital’ programs in the UK, and two transition support programs in Canada. An inductive thematic analysis generated rich descriptions of each program, and comparative analytical activities generated insights across the cases.

Results

Programs provided a range of personalized support for older adults and address many post-discharge needs, including wellbeing assessments, support for instrumental activities of daily living, psychosocial support, and other individualized services directed by the needs and preferences of the service user. Results suggest that these types of programs can act as a ‘safety net’ and promote independent living. Skilled volunteers can positively impact older adults’ experience returning home.

Conclusions

When the programs under study are considered in tandem with existing evidence, it facilitates a discussion of how TSO services could be made available more widely to support older adults in their transition experiences.
External validation of a paediatric SMART triage model for use in resource limited facilities
Authors: Kigo Joyce , Kamau Stephen , Mawji Alishah , Mwaniki Paul , Dunsmuir Dustin , Pillay Yashodani , Zhang Cherri , Pallot Katija , Ogero Morris , Kimutai David , Ouma Mary , Mohamed Ismael , Chege Mary , Thuranira Lydia , Kissoon Niranjan , Ansermino J. Mark , Akech Samuel
Published: June 2023

Introduction

Models for digital triage of sick children at emergency departments of hospitals in resource poor settings have been developed. However, prior to their adoption, external validation should be performed to ensure their generalizability.

Methods

We externally validated a previously published nine-predictor paediatric triage model (SMART Triage) developed in Uganda using data from two hospitals in Kenya. Both discrimination and calibration were assessed, and recalibration was performed by optimizing the intercept for classifying patients into emergency, priority, or non-urgent categories based on low-risk and high-risk thresholds.

Results

A total of 2539 patients were eligible at Hospital 1 and 2464 at Hospital 2, and 5003 for both hospitals combined; admission rates were 8.9%, 4.5%, and 6.8%, respectively. The model showed good discrimination, with area under the receiver-operator curve (AUC) of 0.826, 0.784 and 0.821, respectively. The pre-calibrated model at a low-risk threshold of 8% achieved a sensitivity of 93% (95% confidence interval, (CI):89%-96%), 81% (CI:74%-88%), and 89% (CI:85%–92%), respectively, and at a high-risk threshold of 40%, the model achieved a specificity of 86% (CI:84%–87%), 96% (CI:95%-97%), and 91% (CI:90%-92%), respectively. Recalibration improved the graphical fit, but new risk thresholds were required to optimize sensitivity and specificity.

Conclusion

The Smart Triage model showed good discrimination on external validation but required recalibration to improve the graphical fit of the calibration plot. There was no change in the order of prioritization of patients following recalibration in the respective triage categories. Recalibration required new site-specific risk thresholds that may not be needed if prioritization based on rank is all that is required. The Smart Triage model shows promise for wider application for use in triage for sick children in different settings.

Funder

Wellcome Trust (UK)
Developmental hourglass: Verification by numerical evolution and elucidation by dynamical-systems theory
Authors: Kohsokabe Takahiro , Kuratanai Shigeru , Kaneko Kunihiko
Published: June 2023

Determining the general laws between evolution and development is a fundamental biological challenge. Developmental hourglasses have attracted increased attention as candidates for such laws, but the necessity of their emergence remains elusive. We conducted evolutionary simulations of developmental processes to confirm the emergence of the developmental hourglass and unveiled its establishment. We considered organisms consisting of cells containing identical gene networks that control morphogenesis and evolved them under selection pressure to induce more cell types. By computing the similarity between the spatial patterns of gene expression of two species that evolved from a common ancestor, a developmental hourglass was observed, that is, there was a correlation peak in the intermediate stage of development. The fraction of pleiotropic genes increased, whereas the variance in individuals decreased, consistent with previous experimental reports. Reduction of the unavoidable variance by initial or developmental noise, essential for survival, was achieved up to the hourglass bottleneck stage, followed by diversification in developmental processes, whose timing is controlled by the slow expression dynamics conserved among organisms sharing the hourglass. This study suggests why developmental hourglasses are observed within a certain phylogenetic range of species.

Author Summary

Understanding the intriguing relationship between development and evolution in multicellular organisms has long been a challenge in biology. A recent hypothesis called the developmental hourglass proposes that there is a conserved middle stage during development across species of the same animal group. Despite growing evidence supporting this hypothesis, the underlying mechanisms and reasons for its emergence have remained elusive due to limited experimental data.

To address this gap, we employed numerical evolution of gene regulation networks controlling pattern formation. Remarkably, our simulations revealed that species that diverged relatively recently in phylogeny displayed the highest similarity during the middle stage of development, which gradually diminished as they diverged further phylogenetically. Our findings satisfied not only the criteria of the developmental hourglass but also confirmed several essential characteristics of the developmental hourglass reported in recent experiments. Through theoretical analysis, we further demonstrated that the emergence of the developmental hourglass could be attributed to the acquisition of genes that change slowly and govern developmental processes, which also foster the robustness of development.

By integrating computational simulations, theoretical insights, and previous experimental evidence, our study thus provides a comprehensive understanding of the developmental hourglass, which will unravel the intricate relationship between development and evolution.
Mannose is crucial for mesoderm specification and symmetry breaking in gastruloids
Authors: Dingare Chaitanya , Yang Jenny , Steventon Ben
Published: June 2023

Patterning and growth are fundamental features of embryonic development that must be tightly coordinated during morphogenesis. As metabolism can control cell growth while also providing mechanistic links to developmental signalling pathways, it is ideally placed to enable this coordination. To understand how metabolism impacts early mesoderm specification, we used mouse embryonic stem (ES) cell-derived gastruloids, as these enable temporal control over metabolic manipulations and can be generated in large quantities. Gastruloids show mosaic expression of two glucose transporters,Slc2a1andSlc2a3both of which co-express with the expression of both the mesodermal markerT/Braand the neural markerSox2. To understand the significance of cellular glucose uptake in development, we used the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG). 2-DG specifically blocks the expression ofT/Brawithout affecting the expression ofSox2and abolishes axial elongation in gastruloids. Surprisingly, removing glucose completely from the medium did not phenocopy 2-DG treatment despite a significant decline in glycolytic intermediates occurring under both conditions. As 2-DG can also act as a competitive inhibitor of mannose, we added mannose together with 2-DG and found that it could rescue the mesoderm specification. Together, our results show that while mannose is crucial for mesoderm specification, the glycolytic pathway is dispensable at early stages ofT/Braexpression in gastruloids.
Crystal structure of SUN1-KASH6 reveals an asymmetric LINC complex architecture compatible with nuclear membrane insertion
Authors: Gurusaran Manickam , Erlandsen Benedikte S. , Davies Owen R.
Published: June 2023

The LINC complex transmits cytoskeletal forces into the nucleus to control the structure and movement of nuclear contents. It is formed of nuclear SUN and cytoplasmic KASH proteins, which interact within the nuclear lumen, immediately below the outer nuclear membrane. However, the symmetrical location of KASH molecules within SUN-KASH complexes in previous crystal structures has been difficult to reconcile with the steric requirements for insertion of their immediately upstream transmembrane helices into the outer nuclear membrane. Here, we report the crystal structure of the SUN-KASH complex between SUN1 and JAW1/LRMP (KASH6) in an asymmetric 9:6 configuration. This intertwined assembly involves two distinct KASH conformations such that all six KASH molecules emerge on the same molecular surface. Hence, they are ideally positioned for insertion of upstream sequences into the outer nuclear membrane. Thus, we report the first structure of a SUN-KASH complex that is directly compatible with its biological role.
A novel, precise and high-throughput technology for viroid detection in cannabis (MFDetect™)
Authors: Fernandez i Marti Angel , Parungao Marcus , Selimotic Berin , Farrar Graham , Seyler Tristan , Anand Ajith , Ahmad Riaz
Published: June 2023

Hop latent viroid (HLVd) is a severe disease of cannabis, causing substantial economic losses in plant yield and crop value for growers worldwide. The best way to control the disease is early detection to limit the spread of the viroid in grow facilities. This study describes MFDetect™ as a rapid, highly sensitive, and high-throughput tool for detecting HLVd in the early stages of plant development. Furthermore, we compared MFDetect™ with RT-PCR in a time course experiment using different plant tissue, leaf, petiole, and roots at different plant development stages to demonstrate both technologies are comparable. Our study found leaf tissue is a suitable plant material for HLVd detection, with the viroid titer increasing in the infected leaf tissue with the age of plants. The study showed that other tissue types, including petiole and roots, were equally sensitive to detection via MFDetect™. The assay developed in this research allows the screening of thousands of plants in a week. The assay can be scaled easily to provide the growers with a quick turnaround and cost-effective diagnostic tool for screening many plants and tissue types at different stages of development.
Metformin reduces SARS-CoV-2 in a Phase 3 Randomized Placebo Controlled Clinical Trial
Authors: Bramante Carolyn T , Beckman Kenneth B , Mehta Tanvi , Karger Amy B , Odde David J , Tignanelli Christopher J , Buse John B , Johnson Darrell M , Watson Ray H. B. , Daniel Jerry J , Liebovitz David M , Nicklas Jacinda M , Cohen Kenneth , Puskarich Michael A , Belani Hrishikesh K , Siegel Lianne K , Klatt Nichole R , Anderson Blake , Hartman Katrina M , Rao Via , Hagen Aubrey A , Patel Barkha , Fenno Sarah L , Avula Nandini , Reddy Neha V , Erickson Spencer M , Fricton Regina D. , Lee Samuel , Griffiths Gwendolyn , Pullen Matthew F , Thompson Jennifer L. , Sherwood Nancy , Murray Thomas A. , Rose Michael R. , Boulware David R , Huling Jared D. ,   the COVID-OUT study team
Published: June 2023

Current antiviral treatment options for SARS-CoV-2 infections are not available globally, cannot be used with many medications, and are limited to virus-specific targets.1-3Biophysical modeling of SARS-CoV-2 replication predicted that protein translation is an especially attractive target for antiviral therapy.4Literature review identified metformin, widely known as a treatment for diabetes, as a potential suppressor of protein translation via targeting of the host mTor pathway.5In vitro, metformin has antiviral activity against RNA viruses including SARS-CoV-2.6,7In the COVID-OUT phase 3, randomized, placebo-controlled trial of outpatient treatment of COVID-19, metformin had a 42% reduction in ER visits/hospitalizations/death through 14 days; a 58% reduction in hospitalizations/death through 28 days, and a 42% reduction in Long COVID through 10 months.8,9Here we show viral load analysis of specimens collected in the COVID-OUT trial that the mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (−0.56 log10copies/mL; 95%CI, -1.05 to -0.06, p=0.027) while there was no virologic effect for ivermectin or fluvoxamine vs placebo. The metformin effect was consistent across subgroups and with emerging data.10,11Our results demonstrate, consistent with model predictions, that a safe, widely available,12well-tolerated, and inexpensive oral medication, metformin, can be repurposed to significantly reduce SARS-CoV-2 viral load.
Estimation of the real magnitude of antimicrobial resistance ofMycoplasma genitaliumin Belgium by implementing a prospective surveillance programme
Authors: De Baetselier Irith , Smet Hilde , Kehoe Kaat , Loosen Imelda , Reynders Marijke , Mansoor Iqbal , Filippin Lorenzo , Cauchie Mathieu , Van Even Ellen , Makki Nadia , Schiettekatte Gilberte , Vandewal Wouter , Glibert Bart , Matheeussen Veerle , Van der Beken Yolien , Cartuyvels Reinoud , Steyaert Sophia , Lemmens Ann , Garrino Maria-Grazia , Paridaens Henry , Lazarova Elena , Lissoir Bénédicte , Deffontaine Marine , Heinrichs Amélie , Saegeman Veroniek , Padalko Elizaveta , Lecompte Amaryl , Berghe Wim Vanden , Kenyon Chris , Van den Bossche Dorien
Published: June 2023

Objectives

Antimicrobial resistance ofMycoplasma genitalium(MG) is a growing concern worldwide. Because reliable data on the burden of resistant MG in Belgium are missing, an additional prospective surveillance program was implemented in 2022 to estimate the real burden of resistant MG in Belgium.

Methods

Belgian laboratories (n=21) provided frozen remnants of MG positive samples to the National Reference Centre of Sexually Transmitted Infections from July to November 2022. The presence of macrolide and fluoroquinolones resistance associated mutations (RAMs) was assessed using Sanger sequencing of the 23SrRNA andparCgene. Differences in resistance patterns were correlated with surveillance methodology, socio-demographic and behavioral variables via Fisher’s exact test and logistic regression analysis.

Results

Sequencing for both macrolide and fluoroquinolone RAMs was successful for 232/244 MG positive samples. Over half of the samples were resistant to macrolides (55.2%). All MG in samples from men who have sex with men (MSM) (24/24) were resistant to macrolides. The presence of fluoroquinolone RAMs was estimated to be 26% and did not differ with socio-demographic and sexual behaviour characteristics.

Conclusions

Given the considerable cost of macrolide resistance testing, our data suggest that the use of macrolide resistance testing in MSM does not seem justified in Belgium. However, the lower prevalence of macrolide resistance in other population groups, combined with further emergence of fluoroquinolone resistance provides evidence for macrolide resistance testing in these groups. Continued surveillance of resistance in MG in all groups will be crucial to guide national testing- and treatment strategies.