bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of integrated intrinsic foot muscle exercise with foot core training device on balance and body composition among community-dwelling adults aged 60 and above
Authors: Kao Sheng-Lun , Hsiao Mei-Lan , Wang Jen-Hung , Chen Chen-Sheng , Chen Shin-Yuan , Shiau Yung-Jeng , Yang Chich-Haung
Published: May 2024

Background

Evidence on the effects of plantar intrinsic foot muscle exercise in older adults remains limited. This study aimed to evaluate the effect of an integrated intrinsic foot muscle exercise program with a novel three-dimensional printing foot core training device on balance and body composition in community-dwelling adults aged 60 and above.

Methods

A total of 40 participants aged ≥ 60 years were enrolled in this quasi-experimental, single-group, pretest-posttest design; participants were categorized into two groups, those with balance impairment and those without balance impairment. The participants performed a 4-week integrated intrinsic foot muscle exercise program with a three-dimensional printing foot core training device. The short physical performance battery (SPPB) and timed up and go test were employed to evaluate mobility and balance. A foot pressure distribution analysis was conducted to assess static postural control. The appendicular skeletal muscle mass index and fat mass were measured by a segmental body composition monitor with bioelectrical impedance analysis. The Wilcoxon signed rank test was used to determine the difference before and after the exercise program.

Results

Among the 40 enrolled participants (median age, 78.0 years; female, 80.0%; balance-impaired group, 27.5%), the 95% confidence ellipse area of the center of pressure under the eyes-closed condition was significantly decreased (median pretest: 217.3, interquartile range: 238.4; median posttest: 131.7, interquartile range: 199.5; P = 0.001) after the exercise. Female participants without balance impairment demonstrated a significant increase in appendicular skeletal muscle mass index and a decrease in fat mass. Participants in the balance-impaired group exhibited a significant increase in SPPB.

Conclusions

Integrated intrinsic foot muscle exercise with a three-dimensional printing foot core training device may improve balance and body composition in adults aged 60 and above.

Trial registration

ClinicalTrials.gov ID: NCT05750888 (retrospectively registered 02/03/2023).
Twenty-four-hour physical activity patterns associated with depressive symptoms: a cross-sectional study using big data-machine learning approach
Authors: Nawrin Saida Salima , Inada Hitoshi , Momma Haruki , Nagatomi Ryoichi
Published: May 2024

Background

Depression is a global burden with profound personal and economic consequences. Previous studies have reported that the amount of physical activity is associated with depression. However, the relationship between the temporal patterns of physical activity and depressive symptoms is poorly understood. In this exploratory study, we hypothesize that a particular temporal pattern of daily physical activity could be associated with depressive symptoms and might be a better marker than the total amount of physical activity.

Methods

To address the hypothesis, we investigated the association between depressive symptoms and daily dominant activity behaviors based on 24-h temporal patterns of physical activity. We conducted a cross-sectional study on NHANES 2011–2012 data collected from the noninstitutionalized civilian resident population of the United States. The number of participants that had the whole set of physical activity data collected by the accelerometer is 6613. Among 6613 participants, 4242 participants had complete demography and Patient Health Questionnaire-9 (PHQ-9) questionnaire, a tool to quantify depressive symptoms. The association between activity-count behaviors and depressive symptoms was analyzed using multivariable logistic regression to adjust for confounding factors in sequential models.

Results

We identified four physical activity-count behaviors based on five physical activity-counting patterns classified by unsupervised machine learning. Regarding PHQ-9 scores, we found that evening dominant behavior was positively associated with depressive symptoms compared to morning dominant behavior as the control group.

Conclusions

Our results might contribute to monitoring and identifying individuals with latent depressive symptoms, emphasizing the importance of nuanced activity patterns and their probability of assessing depressive symptoms effectively.
Optical imaging (HandScan) can identify ultrasound remission in rheumatoid arthritis
Authors: Rinkin Charline , Malaise Olivier , Chauveheid Florane , Gerard Caroline , Seidel Laurence , Malaise Michel , Ribbens Clio
Published: May 2024

Background

Identifying remission is of high importance in rheumatoid arthritis (RA) because remission is associated with less structural progression. We investigated the efficacy of a new optical imaging device, HandScan, to identify RA remission, as defined by ultrasound (US).

Methods

61 RA patients were included. Disease activity was evaluated by clinical assessment and US, using gray-scale (GS) and Power Doppler (PD). HandScan determined unitary optical spectral transmission (OST) values for wrists, metacarpophalangeal and proximal interphalangeal joints. At the patient level, three composite HandScan (HS) scores were calculated: total HS score; disease activity score OST (DAS-OST) and DAS-OST without patient global assessment (PtGA). Using ROC curves, we determined HS cut-offs to identify US-defined remission.

Results

At the joint level, unitary OST values significantly correlated with GS synovitis [odds ratio (OR) 2.43, p < 0.0001] and PD positivity (OR 3.72, p = 0.0002 ). At the patient level, total HS score and DAS-OST were significantly associated with all gray-scale US (GSUS) and power doppler US (PDUS) parameters evaluated (synovitis number and grade, synovial thickness, PD grade) (p < 0.05). The cut-off to identify US-defined remission at the joint level was of 0.92, giving an 81% sensitivity and a 96% positive predictive value (PPV). At the patient level, ROC-curves failed to identify a robust cut-off for the total HS score, but did identify a cut-off (3.68) for DAS-OST to identify US-defined remission, but with lower sensitivity (75%), specificity (56%) and PPV (67%).

Conclusions

HandScan is a non-invasive optical imaging technique providing OST values that correlate with GSUS and PDUS parameters. In addition, HandScan is able to reliably identify US-defined remission in RA at the joint level, with a good sensitivity and high PPV. At the patient level, HandScan DAS-OST can also determine US remission (while total HS score failed to do so), but with lower performance.
GRAVEN: a database of teaching method that applies gestures to represent the neurosurgical approach’s blood vessels and nerves
Authors: Xuan Hanwen , Zhong Junzhe , Wang Xinyu , Song Yu , Shen Ruofei , Liu Yuxiang , Zhang Sijia , Cai Jinquan , Liu Meichen
Published: May 2024

Background

In this era of rapid technological development, medical schools have had to use modern technology to enhance traditional teaching. Online teaching was preferred by many medical schools. However due to the complexity of intracranial anatomy, it was challenging for the students to study this part online, and the students were likely to be tired of neurosurgery, which is disadvantageous to the development of neurosurgery. Therefore, we developed this database to help students learn better neuroanatomy.

Main body

The data were sourced from Rhoton’s Cranial Anatomy and Surgical Approaches and Neurosurgery Tricks of the Trade in this database. Then we designed many hand gesture figures connected with the atlas of anatomy. Our database was divided into three parts: intracranial arteries, intracranial veins, and neurosurgery approaches. Each section below contains an atlas of anatomy, and gestures represent vessels and nerves. Pictures of hand gestures and atlas of anatomy are available to view on GRAVEN (www.graven.cn) without restrictions for all teachers and students. We recruited 50 undergraduate students and randomly divided them into two groups: using traditional teaching methods or GRAVEN database combined with above traditional teaching methods. Results revealed a significant improvement in academic performance in using GRAVEN database combined with traditional teaching methods compared to the traditional teaching methods.

Conclusion

This database was vital to help students learn about intracranial anatomy and neurosurgical approaches. Gesture teaching can effectively simulate the relationship between human organs and tissues through the flexibility of hands and fingers, improving anatomy interest and education.
Improved nonparametric survival prediction using CoxPH, Random Survival Forest & DeepHit Neural Network
Authors: Asghar Naseem , Khalil Umair , Ahmad Basheer , Alshanbari Huda M. , Hamraz Muhammad , Ahmad Bakhtiyar , Khan Dost Muhammad
Published: May 2024

In recent times, time-to-event data such as time to failure or death is routinely collected alongside high-throughput covariates. These high-dimensional bioinformatics data often challenge classical survival models, which are either infeasible to fit or produce low prediction accuracy due to overfitting. To address this issue, the focus has shifted towards introducing a novel approaches for feature selection and survival prediction. In this article, we propose a new hybrid feature selection approach that handles high-dimensional bioinformatics datasets for improved survival prediction. This study explores the efficacy of four distinct variable selection techniques: LASSO, RSF-vs, SCAD, and CoxBoost, in the context of non-parametric biomedical survival prediction. Leveraging these methods, we conducted comprehensive variable selection processes. Subsequently, survival analysis models—specifically CoxPH, RSF, and DeepHit NN—were employed to construct predictive models based on the selected variables. Furthermore, we introduce a novel approach wherein only variables consistently selected by a majority of the aforementioned feature selection techniques are considered. This innovative strategy, referred to as the proposed method, aims to enhance the reliability and robustness of variable selection, subsequently improving the predictive performance of the survival analysis models. To evaluate the effectiveness of the proposed method, we compare the performance of the proposed approach with the existing LASSO, RSF-vs, SCAD, and CoxBoost techniques using various performance metrics including integrated brier score (IBS), concordance index (C-Index) and integrated absolute error (IAE) for numerous high-dimensional survival datasets. The real data applications reveal that the proposed method outperforms the competing methods in terms of survival prediction accuracy.
A longitudinal qualitative exploration of Victorian healthcare workers’ and organisations’ evolving views and experiences during COVID-19
Authors: McGuinness Sarah L. , Eades Owen , Zhong Shannon , Clifford Sharon , Fisher Jane , Kelsall Helen L. , Kirkman Maggie , Russell Grant , Skouteris Helen , Leder Karin ,   for the COVIC-HA investigator group, Cameron Peter A. , Forbes Andrew , Grantham Kelsey , Hodgson Carol L. , Hunter Peter , Kasza Jessica , Russo Philip L. , Sim Malcolm , Singh Kasha , Smith Karen L. , Stuart Rhonda L. , Teede Helena J. , Trauer James M. , Udy Andrew , Zoungas Sophia
Published: May 2024

Background

The COVID-19 pandemic has profoundly impacted individuals, society, and healthcare organisations worldwide. Recent international research suggests that concerns, needs, and experiences of healthcare workers (HCWs) have evolved throughout the pandemic. This longitudinal qualitative study explored the evolving views and experiences of Victorian healthcare workers (HCWs) and organisational key personnel during the coronavirus disease (COVID-19) pandemic.

Methods

We recruited participants from the Coronavirus in Victorian Health and Aged care workers (COVIC-HA) study cohort. We conducted two rounds of semi-structured interviews with HCWs and organisational key personnel from three different healthcare settings (hospital, aged care and primary care) in Victoria, Australia, in May-July 2021 and May-July 2022. Data were analysed thematically using trajectory and recurrent cross-sectional approaches, guided by a temporal change framework.

Results

Twelve HCWs and five key personnel from various professional roles participated in interviews at both timepoints. Expected themes derived from mid-2021 interviews (navigating uncertainty, maintaining service delivery, and addressing staff needs) evolved over time. Concerns shifted from personal health and safety to workforce pressures, contributing to HCW burnout and fatigue and ongoing mental health support needs. New themes emerged from mid-2022 interviews, including managing ongoing COVID-19 impacts and supporting the healthcare workforce into the future. Clear and consistent communication, stable guidelines and forward-looking organisational responses were considered crucial.

Conclusions

Our longitudinal qualitative study highlighted the evolving impact of the COVID-19 pandemic on HCWs’ perceptions, health and wellbeing and uncovered long-term sector vulnerabilities. Analysing HCW experiences and key personnel insights over time and across different pandemic phases provided crucial insights for policymakers to protect the healthcare workforce. Findings emphasise the need for proactive strategies that prioritise HCWs’ wellbeing and workforce sustainability. Policy makers must invest in HCW health and wellbeing initiatives alongside healthcare system improvements to ensure resilience and capacity to meet future challenges.

Trial registration

This study was approved through the Victorian Streamlined Ethical Review Process (SERP: Project Number 68,086) and registered with ANZCTR (ACTRN12621000533897) on 6 May 2021.
Detection of a novel pathogenic variant in KCNH2 associated with long QT syndrome 2 using whole exome sequencing
Authors: Kohansal Erfan , Naderi Niloofar , Fazelifar Amir Farjam , Maleki Majid , Kalayinia Samira
Published: May 2024

Background

Long QT syndrome (LQTS) is a cardiac channelopathy characterized by impaired myocardial repolarization that predisposes to life-threatening arrhythmias. This study aimed to elucidate the genetic basis of LQTS in an affected Iranian family using whole exome sequencing (WES).

Methods

A 37-year-old woman with a personal and family history of sudden cardiac arrest and LQTS was referred for genetic study after losing her teenage daughter due to sudden cardiac death (SCD). WES was performed and variants were filtered and prioritized based on quality, allele frequency, pathogenicity predictions, and conservation scores. Sanger sequencing confirmed segregation in the family.

Results

WES identified a novel heterozygous frameshift variant (NM_000238.4:c.3257_3258insG; pGly1087Trpfs*32) in the KCNH2 encoding the α-subunit of the rapid delayed rectifier potassium channel responsible for cardiac repolarization. This variant, predicted to cause a truncated protein, is located in the C-terminal region of the channel and was classified as likely pathogenic based on ACMG guidelines. The variant was absent in population databases and unaffected family members.

Conclusion

This study reports a novel KCNH2 frameshift variant in an Iranian family with LQTS, expanding the spectrum of disease-causing variants in this gene. Our findings highlight the importance of the C-terminal region in KCNH2 for proper channel function and the utility of WES in identifying rare variants in genetically heterogeneous disorders like LQTS. Functional characterization of this variant is warranted to fully elucidate its pathogenic mechanisms and inform personalized management strategies.
Adherence to low-dose methotrexate in children with juvenile idiopathic arthritis using a sensitive methotrexate assay
Authors: Möhlmann Julia E. , de Roock Sytze , Egas Annelies C. , Weijden Evelien ter , Doeleman Martijn J. H. , Huitema Alwin D. R. , van Luin Matthijs , Swart Joost F.
Published: May 2024

Background

Low-dose weekly methotrexate (MTX) is the mainstay of treatment in juvenile idiopathic arthritis. Unfortunately, a substantial part of patients has insufficient efficacy of MTX. A potential cause of this inadequate response is suboptimal drug adherence. The aim of this study was to assess MTX adherence in juvenile idiopathic arthritis patients by quantification of MTX concentrations in plasma. Secondly, the association between MTX concentrations and either self-reported adherence issues, or concomitant use of biologics was examined.

Methods

This was a retrospective, observational study using plasma samples from juvenile idiopathic arthritis patients. An ultrasensitive liquid chromatography-tandem mass spectrometry method was developed for quantification of MTX and its metabolite 7-hydroxy-MTX in plasma. The determined MTX plasma concentrations in juvenile idiopathic arthritis patients were compared with corresponding adherence limits, categorising them as either adherent or possibly non-adherent to MTX therapy.

Results

Plasma samples of 43 patients with juvenile idiopathic arthritis were analysed. Adherence to MTX in this population was 88% shortly after initiation of MTX therapy and decreased to 77% after one year of treatment. Teenagers were more at risk for non-adherence (p = 0.002). We could not find an association between MTX adherence with either self-reported adherence issues, nor with the use of concomitant biological treatment (p = 1.00 and p = 0.27, respectively; Fisher’s Exact).

Conclusions

Quantification of MTX in plasma is a feasible and objective method to assess adherence in patients using low-dose weekly MTX. In clinical practice, the use of this method could be a helpful tool for physicians to refute or support suspicion of non-adherence to MTX therapy.
Successful chimney endovascular aortic repair with reconstruction of three visceral branches for huge saccular juxtarenal abdominal aortic aneurysm after trans-thoracoabdominal esophagectomy
Authors: Goto Takasumi , Fujimura Hironobu , Shintani Takashi , Shibuya Takashi
Published: May 2024

Background

Conventional graft replacement for a juxtarenal abdominal aortic aneurysm (JRAAA) remains challenging for high-risk patients since it often requires the reconstruction of some visceral arteries.

Case Presentation

A 76-year-old woman was diagnosed with an 87 × 48 mm saccular JRAAA. Open graft replacement was contraindicated because of frailty and a past history of trans-thoracoabdominal esophagectomy. Chimney endovascular aortic repair (ChEVAR) with three chimney endografts was successfully performed without any endoleaks, and each visceral circulation was kept intact. The patient was discharged uneventfully on postoperative day 8. Significant shrinkage of the aneurysmal sac and preservation of flow through each chimney graft were observed on computed tomography 6 months postoperatively, with no significant increase in serum creatinine levels on laboratory testing.

Conclusions

ChEVAR can be a useful surgical option instead of conventional operations, especially for high-risk cases.
A healthcare claims analysis to identify and characterize patients with suspected X-Linked Myotubular Myopathy (XLMTM) in the Brazilian Healthcare System
Authors: Souza Paulo Victor Sgobbi , Haselkorn Tmirah , Baima Jader , Oliveira Renato Watanabe , Hernández Fabián , Birck Marina G. , França Marcondes C.
Published: May 2024

Background

X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital disease, which is not well-defined. To our knowledge, no studies characterizing the XLMTM disease burden have been conducted in Brazil. We identified and described patients with suspected XLMTM using administrative claims data from the Brazilian public healthcare system.

Methods

Data from 2015 to 2019 were extracted from the DATASUS database. As no XLMTM-specific ICD-10 code was available, a stepwise algorithm was applied to identify patients with suspected XLMTM by selecting male patients with a congenital myopathies code (G71.2), aged < 18 years at index date (first claim of G71.2), with an associated diagnostic procedure (muscle biopsy/genetic test) and without spinal muscular atrophy or Duchenne muscular dystrophy. We attempted to identify patients with suspected severe XLMTM based on use of both respiratory and feeding support, which are nearly universal in the care of XLMTM patients. Analyses were performed for the overall cohort and stratified by age at index date < 5 years old and ≥ 5 years old.

Results

Of 173 patients with suspected XLMTM identified, 39% were < 5 years old at index date. Nearly all (N = 166) patients (96%) were diagnosed by muscle biopsy (91% of patients < 5 years old and 99% of patients ≥ 5 years old), six (3.5%) were diagnosed by clinical evaluation (8% of patients < 5 years old and 1% of patients ≥ 5 years old), and one was diagnosed by a genetic test. Most patients lived in Brasilia (n = 55), São Paulo (n = 33) and Minas Gerais (n = 27). More than 85% of patients < 5 years old and approximately 75% of patients ≥ 5 years old had physiotherapy at the index date. In both age groups, nearly 50% of patients required hospitalization at some point and 25% required mobility support. Respiratory and feeding support were required for 3% and 12% of patients, respectively, suggesting that between 5 and 21 patients may have had severe XLMTM.

Conclusion

In this real-world study, genetic testing for XLMTM appears to be underutilized in Brazil and may contribute to underdiagnosis of the disease. Access to diagnosis and care is limited outside of specific regions with specialized clinics and hospitals. Substantial use of healthcare resources included hospitalization, physiotherapy, mobility support, and, to a lesser extent, feeding support and respiratory support.
Mimicking chronic alcohol effects through a controlled and sustained ethanol release device
Authors: Kim Wanil , Chu Jin-Ok , Kim Do-Yeon , Lee Soo-Hyeon , Choi Chang-Hyung , Lee Kyung-Ha
Published: May 2024

Alcohol consumption, a pervasive societal issue, poses considerable health risks and socioeconomic consequences. Alcohol-induced hepatic disorders, such as fatty liver disease, alcoholic hepatitis, chronic hepatitis, liver fibrosis, and cirrhosis, underscore the need for comprehensive research. Existing challenges in mimicking chronic alcohol exposure in cellular systems, attributed to ethanol evaporation, necessitate innovative approaches. In this study, we developed a simple, reusable, and controllable device for examining the physiological reactions of hepatocytes to long-term alcohol exposure. Our approach involved a novel device designed to continuously release ethanol into the culture medium, maintaining a consistent ethanol concentration over several days. We evaluated device performance by examining gene expression patterns and cytokine secretion alterations during long-term exposure to ethanol. These patterns were correlated with those observed in patients with alcoholic hepatitis. Our results suggest that our ethanol-releasing device can be used as a valuable tool to study the mechanisms of chronic alcohol-mediated hepatic diseases at the cellular level. Our device offers a practical solution for studying chronic alcohol exposure, providing a reliable platform for cellular research. This innovative tool holds promise for advancing our understanding of the molecular processes involved in chronic alcohol-mediated hepatic diseases. Future research avenues should explore broader applications and potential implications for predicting and treating alcohol-related illnesses.
Phenotypic variability and management of patients with mosaic monosomy X and Y chromosome material: a case series
Authors: Fredj Myriam Ben , Messaoud Marwa , Youssef Sabrine Ben , Mani Salma , Laaribi Syrine , Sakka Rania , Hmida Hayet Ben , Ksiaa Amine , Mekki Mongi , Belghith Mohsen , Sahnoun Lassaad
Published: May 2024

Background

we aim to discuss the origin and the differences of the phenotypic features and the management care of rare form of disorder of sex development due to Mosaic monosomy X and Y chromosome materiel.

Methods

We report our experience with patients harboring mosaic monosomy X and Y chromosome material diagnosed by blood cells karyotypes and cared for in our department from 2005 to 2022.

Results

We have included five infants in our study. The current average age was 8 years. In four cases, the diagnosis was still after born and it was at the age of 15 years in one case. Physical examination revealed a variable degree of virilization, ranging from a normal male phallus with unilateral ectopic gonad to ambiguous with a genital tubercle and bilateral not palpable gonads in four cases and normal female external genitalia in patient 5. Karyotype found 45, X/46, XY mosaicism in patient 1 and 2 and 45, X/46, X, der (Y) mosaicism in patient 3, 4 and 5. Three cases were assigned to male gender and two cases were assigned to female. After radiologic and histologic exploration, four patients had been explored by laparoscopy to perform gonadectomy in two cases and Mullerian derivative resection in the other. Urethroplasty was done in two cases of posterior hypospadias. Gender identity was concordant with the sex of assignment at birth in only 3 cases.

Conclusion

Because of the phenotypic heterogeneity of this sexual disorders and the variability of its management care, then the decision should rely on a multidisciplinary team approach.
Synthesis and antitumor activity of dolutegravir derivatives bearing 1,2,3-triazole moieties
Authors: Hou Xixi , Mao Longfei , Guo Yajie , Wang Lan , Peng Lizeng , Wang Huili , Yang Jianxue , Li Sanqiang , Li Yue-Ming
Published: May 2024

Modification of marketed drugs is an important way to develop drugs because its safety and clinical applicability. Oxygen-nitrogen heterocycles are a class of important active substances discovered in the process of new drug development. Dolutegravir, an HIV drug with a nitrogen-oxygen heterocycle structure, has the potential ability to inhibit cell survival. In order to find and explore novel anti-tumor drugs, new dolutegravir derivatives bearing different 1,2,3-triazole moieties were prepared via click reactions. In vitro biological experiments performed in several lung cancer cell lines suggested that these novel compounds displayed potent anti-tumor ability. Especially, the compound 9e with a substituent of 2-methyl-3-nitrophenyl and the compound 9p with a substituent of 3-trifluoromethylphenyl were effective against PC-9 cell line with IC50 values of 3.83 and 3.17 µM, respectively. Moreover, compounds 9e and 9p were effective against H460 and A549 cells. Further studies suggested that compounds 9e and 9p could induce cancer cell apoptosis in PC-9 and H460, inhibit cancer cell proliferation, change the cell cycle, and increase the level of reactive oxygen species (ROS) which further induce tumor cell apoptosis. In addition, compounds 9e and 9p increased LC3 protein expression which was the key regulator in autophagy signaling pathway in PC-9 cells. Compound 9e also showed low toxicity against normal cells, and could be regarded as an interesting lead compound for further structure optimization.
Contribution of parasite and host genotype to immunopathology of schistosome infections
Authors: Jutzeler Kathrin S. , Le Clec’h Winka , Chevalier Frédéric D. , Anderson Timothy J. C.
Published: May 2024

Background

The role of pathogen genotype in determining disease severity and immunopathology has been studied intensively in microbial pathogens including bacteria, fungi, protozoa and viruses but is poorly understood in parasitic helminths. The medically important blood fluke Schistosoma mansoni is an excellent model system to study the impact of helminth genetic variation on immunopathology. Our laboratory has demonstrated that laboratory schistosome populations differ in sporocyst growth and cercarial production in the intermediate snail host and worm establishment and fecundity in the vertebrate host. Here, we (i) investigate the hypothesis that schistosome genotype plays a significant role in immunopathology and related parasite life history traits in the vertebrate mouse host and (ii) quantify the relative impact of parasite and host genetics on infection outcomes.

Methods

We infected BALB/c and C57BL/6 mice with four different laboratory schistosome populations from Africa and the Americas. We quantified disease progression in the vertebrate host by measuring body weight and complete blood count (CBC) with differential over a 12-week infection period. On sacrifice, we assessed parasitological (egg and worm counts, fecundity), immunopathological (organ measurements and histopathology) and immunological (CBC with differential and cytokine profiles) characteristics to determine the impact of parasite and host genetics.

Results

We found significant variation between parasite populations in worm numbers, fecundity, liver and intestine egg counts, liver and spleen weight, and fibrotic area but not in granuloma size. Variation in organ weight was explained by egg burden and intrinsic parasite factors independent of egg burden. We found significant variation between infected mouse lines in cytokine levels (IFN-γ, TNF-α), eosinophils, lymphocytes and monocyte counts.

Conclusions

This study showed that both parasite and host genotype impact the outcome of infection. While host genotype explains most of the variation in immunological traits, parasite genotype explains most of the variation in parasitological traits, and both host and parasite genotypes impact immunopathology outcomes.

Graphical Abstract
Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes
Authors: Kim Yong Sung , Unno Tatsuya , Park Seon-Young , Chung Jin Ook , Choi Yoo-Duk , Lee Su-Mi , Cho Seong Hyun , Kim Dong Hyun , Kim Hyun-Soo , Jung Young Do
Published: May 2024

Background/aims

Bile reflux (BR) can influence the gastric environment by altering gastric acidity and possibly the gastric microbiota composition. This study investigated the correlation between bile acids and microbial compositions in the gastric juice of 50 subjects with differing gastric pathologies.

Methods

This study included 50 subjects, which were categorized into three groups based on the endoscopic BR grading system. The primary and secondary bile acid concentrations in gastric juice samples were measured, and microbiota profiling was conducted using 16 S rRNA gene sequencing.

Results

Significant differences were observed in each bile acid level in the three endoscopic BR groups (P < 0.05). The Shannon index demonstrated a significant decrease in the higher BR groups (P < 0.05). Analysis of the β-diversity revealed that BR significantly altered the gastric microbiota composition. The presence of neoplastic lesions and the presence of H. pylori infection impacted the β-diversity of the gastric juice microbiota. The abundance of the Streptococcus and Lancefielfdella genera exhibited positive correlations for almost all bile acid components(P < 0.05). In addition, the abundance of Slobacterium, Veillonella, and Schaalia showed positive correlations with primary unconjugated bile acids (P < 0.05).

Conclusion

Changes in microbial diversity in the gastric juice were associated with BR presence in the stomach. This result suggests that the degree of BR should be considered when studying the gastric juice microbiome.
T2-weighted imaging-based deep-learning method for noninvasive prostate cancer detection and Gleason grade prediction: a multicenter study
Authors: Jin Liang , Yu Zhuo , Gao Feng , Li Ming
Published: May 2024

Objectives

To noninvasively detect prostate cancer and predict the Gleason grade using single-modality T2-weighted imaging with a deep-learning approach.

Methods

Patients with prostate cancer, confirmed by histopathology, who underwent magnetic resonance imaging examinations at our hospital during September 2015–June 2022 were retrospectively included in an internal dataset. An external dataset from another medical center and a public challenge dataset were used for external validation. A deep-learning approach was designed for prostate cancer detection and Gleason grade prediction. The area under the curve (AUC) was calculated to compare the model performance.

Results

For prostate cancer detection, the internal datasets comprised data from 195 healthy individuals (age: 57.27 ± 14.45 years) and 302 patients (age: 72.20 ± 8.34 years) diagnosed with prostate cancer. The AUC of our model for prostate cancer detection in the validation set (n = 96, 19.7%) was 0.918. For Gleason grade prediction, datasets comprising data from 283 of 302 patients with prostate cancer were used, with 227 (age: 72.06 ± 7.98 years) and 56 (age: 72.78 ± 9.49 years) patients being used for training and testing, respectively. The external and public challenge datasets comprised data from 48 (age: 72.19 ± 7.81 years) and 91 patients (unavailable information on age), respectively. The AUC of our model for Gleason grade prediction in the training set (n = 227) was 0.902, whereas those of the validation (n = 56), external validation (n = 48), and public challenge validation sets (n = 91) were 0.854, 0.776, and 0.838, respectively.

Conclusion

Through multicenter dataset validation, our proposed deep-learning method could detect prostate cancer and predict the Gleason grade better than human experts.

Critical relevance statement

Precise prostate cancer detection and Gleason grade prediction have great significance for clinical treatment and decision making.

Key Points

Prostate segmentation is easier to annotate than prostate cancer lesions for radiologists.

Our deep-learning method detected prostate cancer and predicted the Gleason grade, outperforming human experts.

Non-invasive Gleason grade prediction can reduce the number of unnecessary biopsies.

Graphical Abstract
Optimizing ultrafast dynamic contrast-enhanced MRI scan duration in the differentiation of benign and malignant breast lesions
Authors: Cao Ying , Huang Yao , Chen Xianglong , Wang Wei , Chen Huifang , Yin Ting , Nickel Dominik , Li Changchun , Shao Junhua , Zhang Shi , Wang Xiaoxia , Zhang Jiuquan
Published: May 2024

Objective

To determine the optimal scan duration for ultrafast DCE-MRI in effectively differentiating benign from malignant breast lesions.

Methods

The study prospectively recruited participants who underwent breast ultrafast DCE-MRI from September 2021 to March 2023. A 30-phase breast ultrafast DCE-MRI on a 3.0-T MRI system was conducted with a 4.5-s temporal resolution. Scan durations ranged from 40.5 s to 135.0 s, during which the analysis is performed at three-phase intervals, forming eight dynamic sets (scan duration [SD]40.5s: 40.5 s, SD54s: 54.0 s, SD67.5s: 67.5 s, SD81s: 81.0 s, SD94.5s: 94.5 s, SD108s: 108.0 s, SD121.5s: 121.5 s, and SD135s: 135.0 s). Two ultrafast DCE-MRI parameters, maximum slope (MS) and initial area under the curve in 60 s (iAUC), were calculated for each dynamic set and compared between benign and malignant lesions. Areas under the receiver operating characteristic curve (AUCs) were used to assess their diagnostic performance.

Results

A total of 140 women (mean age, 47 ± 11 years) with 151 lesions were included. MS and iAUC from eight dynamic sets exhibited significant differences between benign and malignant lesions (all p < 0.05), except iAUC at SD40.5s. The AUC of MS (AUC = 0.804) and iAUC (AUC = 0.659) at SD67.5s were significantly higher than their values at SD40.5s (AUC = 0.606 and 0.516; corrected p < 0.05). No significant differences in AUCs for MS and iAUC were observed from SD67.5s to SD135s (all corrected p > 0.05).

Conclusions

Ultrafast DCE-MRI with a 67.5-s scan duration appears optimal for effectively differentiating malignant from benign breast lesions.

Critical relevance statement

By evaluating scan durations (40.5–135 s) and analyzing two ultrafast DCE-MRI parameters, we found a scan duration of 67.5 s optimal for discriminating between these lesions and offering a balance between acquisition time and diagnostic efficacy.

Key Points

Ultrafast DCE-MRI can effectively differentiate malignant from benign breast lesions.

A minimum of 67.5-sec ultrafast DCE-MRI scan duration is required to differentiate benign and malignant lesions.

Extending the scan duration beyond 67.5 s did not significantly improve diagnostic accuracy.

Graphical Abstract
CXCL10 is a crucial chemoattractant for efficient intranasal delivery of mesenchymal stem cells to the neonatal hypoxic-ischemic brain
Authors: Hermans Eva C. , Donega Vanessa , Heijnen Cobi J. , de Theije Caroline G.M. , Nijboer Cora H.
Published: May 2024

Background

Hypoxic-Ischemic Encephalopathy (HIE) is a leading cause of mortality and morbidity in newborns. Recent research has shown promise in using intranasal mesenchymal stem cell (MSC) therapy if administered within 10 days after Hypoxia-Ischemia (HI) in neonatal mice. MSCs migrate from the nasal cavity to the cerebral lesion in response to chemotactic cues. Which exact chemokines are crucial for MSC guidance to the HI lesion is currently not fully understood. This study investigates the role of CXCL10 in MSC migration towards the HI-injured brain.

Methods

HI was induced in male and female 9-day-old C57BL/6 mice followed by intranasal MSC treatment at day 10 or 17 post-HI. CXCL10 protein levels, PKH26-labeled MSCs and lesion size were assessed by ELISA, immunofluorescent imaging and MAP2 staining respectively. At day 17 post-HI, when CXCL10 levels were reduced, intracranial CXCL10 injection and intranasal PKH26-labeled MSC administration were combined to assess CXCL10-guided MSC migration. MSC treatment efficacy was evaluated after 18 days, measuring lesion size, motor outcome (cylinder rearing task), glial scarring (GFAP staining) and neuronal density (NeuN staining) around the lesion. Expression of the receptor for CXCL10, i.e. CXCR3, on MSCs was confirmed by qPCR and Western Blot. Moreover, CXCL10-guided MSC migration was assessed through an in vitro transwell migration assay.

Results

Intranasal MSC treatment at day 17 post-HI did not reduce lesion size in contrast to earlier treatment timepoints. Cerebral CXCL10 levels were significantly decreased at 17 days versus 10 days post-HI and correlated with reduced MSC migration towards the brain. In vitro experiments demonstrated that CXCR3 receptor inhibition prevented CXCL10-guided migration of MSCs. Intracranial CXCL10 injection at day 17 post-HI significantly increased the number of MSCs reaching the lesion which was accompanied by repair of the HI lesion as measured by reduced lesion size and glial scarring, and an increased number of neurons around the lesion.

Conclusions

This study underscores the crucial role of the chemoattractant CXCL10 in guiding MSCs to the HI lesion after intranasal administration. Strategies to enhance CXCR3-mediated migration of MSCs may improve the efficacy of MSC therapy or extend its regenerative therapeutic window.
Early adversity causes sex-specific deficits in perforant pathway connectivity and contextual memory in adolescent mice
Authors: Islam Rafiad , White Jordon D. , Arefin Tanzil M. , Mehta Sameet , Liu Xinran , Polis Baruh , Giuliano Lauryn , Ahmed Sahabuddin , Bowers Christian , Zhang Jiangyang , Kaffman Arie
Published: May 2024

Background

Early life adversity impairs hippocampal development and function across diverse species. While initial evidence indicated potential variations between males and females, further research is required to validate these observations and better understand the underlying mechanisms contributing to these sex differences. Furthermore, most of the preclinical work in rodents was performed in adult males, with only few studies examining sex differences during adolescence when such differences appear more pronounced. To address these concerns, we investigated the impact of limited bedding (LB), a mouse model of early adversity, on hippocampal development in prepubescent and adolescent male and female mice.

Methods

RNA sequencing, confocal microscopy, and electron microscopy were used to evaluate the impact of LB and sex on hippocampal development in prepubescent postnatal day 17 (P17) mice. Additional studies were conducted on adolescent mice aged P29-36, which included contextual fear conditioning, retrograde tracing, and ex vivo diffusion magnetic resonance imaging (dMRI).

Results

More severe deficits in axonal innervation and myelination were found in the perforant pathway of prepubescent and adolescent LB males compared to LB female littermates. These sex differences were due to a failure of reelin-positive neurons located in the lateral entorhinal cortex (LEC) to innervate the dorsal hippocampus via the perforant pathway in males, but not LB females, and were strongly correlated with deficits in contextual fear conditioning.

Conclusions

LB impairs the capacity of reelin-positive cells located in the LEC to project and innervate the dorsal hippocampus in LB males but not female LB littermates. Given the critical role that these projections play in supporting normal hippocampal function, a failure to establish proper connectivity between the LEC and the dorsal hippocampus provides a compelling and novel mechanism to explain the more severe deficits in myelination and contextual freezing found in adolescent LB males.
Breast cancer incidence, stage distribution, and treatment shifts during the 2020 COVID-19 pandemic: a nationwide population-level study
Authors: Peacock Hanna M. , van Walle Lien , Silversmit Geert , Neven Patrick , Han Sileny N. , Van Damme Nancy
Published: May 2024

Background

The first COVID-19 wave in 2020 necessitated temporary suspension of non-essential medical services including organized cancer screening programs in Belgium. This study assessed the impact of the pandemic on breast cancer (BC) incidence, stage at diagnosis, and management in Belgium in 2020.

Methods

All Belgian residents diagnosed with in situ or invasive BC in 2015–2020 in the nationwide, population-based cancer registry database were included. Incidence trends for 2015–2019 were extrapolated to predict incidence and stage distribution for 2020 and compared with the observed values. National healthcare reimbursement data were used to examine treatment strategies. Exact tumor diameter and nodal involvement, extracted from pathology reports, were analyzed for 2019 and 2020.

Results

74,975 tumors were selected for analysis of incidence and clinical stage. Invasive BC incidence declined by -5.0% in 2020, with a drop during the first COVID-19 wave (Mar-Jun; -23%) followed by a rebound (Jul-Dec; +7%). Predicted and observed incidence (in situ + invasive) was not different in patients < 50 years. In the 50–69 and 70 + age groups, significant declines of -4.1% and − 8.4% respectively were found. Excess declines were seen in clinical stage 0 and I in Mar-Jun, without excess increases in clinical stage II-IV tumors in Jul-Dec. There was no increase in average tumor diameter or nodal involvement in 2020. Patients diagnosed in Mar-Jun received significantly more neoadjuvant therapy, particularly neoadjuvant hormonal therapy for patients with clinical stage I-II BC.

Conclusions

BC incidence decline in 2020 in Belgium was largely restricted to very early-stage BC and patients aged 50 and over. Delayed diagnosis did not result in an overall progression to higher stage at diagnosis in 2020. Observed treatment adaptations in Belgium were successful in prioritizing patients for surgery while preventing tumor progression in those with surgical delay. Continuation of monitoring BC incidence and stage in the future is crucial.
Mothers’ evaluations of fathers’ contributions to raising children with autism spectrum disorder in the United Arab Emirates
Authors: Opoku Maxwell Peprah , Mohamed Ahmed , Safi Mohammed , Belbase Shashidhar , Al Mughairbi Fadwa , Xie Quizhi , Al Shatheli Mahmoud
Published: May 2024

Background

Autism spectrum disorder (ASD) is a lifelong neurological condition which results in social skill deficits, communication difficulties, and restrictive and repetitive behaviour. The difficulties associated with parenting children with ASD have been studied extensively, mainly from the perspectives of mothers. The extent of involvement of fathers in the raising of children with ASD has received limited scholarly attention, especially in non-Western contexts such as the United Arab Emirates.

Objectives

This study asked mothers to evaluate the involvement of fathers in the development of children with ASD.

Methods

In all, 240 mothers completed the Fathers’ Involvement in Development and Rehabilitation Scale, designed based on a review of literature on the construct of involvement, namely attitude, participation in training, and support domains. The data were subjected to computation of mean scores, multivariate analysis of variance, hierarchical regression, and moderation analyses.

Results

The results suggested that fathers held positive attitudes and provided substantial support to their children with ASD. However, mothers were ambivalent regarding the participation of fathers in training to support the development of their children. Differences were also observed between participants according to marital status, location, child gender, and ASD severity.

Conclusion

Recommendations for targeted training for fathers and other study implications are discussed.
A structural model of EFL teachers’ physical activity, emotion regulation, and competence for online teaching
Authors: Cheng Peng Yang Zi , Liu Hai
Published: May 2024

Background

The COVID-19 pandemic has prompted a rapid shift to online teaching, placing unprecedented demands on educators’ physical and mental well-being. However, the relationship between English as a Foreign Language (EFL) teachers’ physical activity, emotion regulation, and competence for online teaching remains underexplored.

Objectives

This study aimed to investigate the interplay between EFL teachers’ physical activity, emotion regulation strategies, and competence for online teaching.

Results

Structural equation modeling revealed significant direct and indirect effects, indicating that physical activity positively influences emotion regulation, which, in turn, enhances teachers’ competence for online instruction. Furthermore, emotion regulation was found to mediate the relationship between physical activity and online teaching competence.

Conclusions

These findings underscore the importance of promoting physical activity among EFL teachers as a means to enhance their emotion regulation skills and competence for online teaching, particularly in the context of the COVID-19 pandemic.

Implications

The study highlights the need for targeted interventions aimed at supporting EFL teachers’ well-being and professional development, with implications for educational policies, teacher training programs, and institutional support structures in the digital learning landscape.