bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractAlcohol 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

Abstract
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

AbstractModification 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.