bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing a quality and safety assessment framework for Iran’s military hospitals
Authors: Markazi-Moghaddam Nader , Mohammadimehr Mojgan , Nikoomanesh Mahdi , Rezapour Ramin , Jame Sanaz Zargar Balaye 
Published: July 2024

Abstract
Background
The first crucial step towards military hospitals performance improvement is to develop a local and scientific tool to assess quality and safety based on the context and aims of military hospitals. This study introduces a Quality and Safety Assessment Framework (Q&SAF) for Iran’s military hospitals.

Methods
This is a literature review which continued with a qualitative study. The Q&SAF for Iran’s military hospitals was developed initially, through a review of the WHO’s framework for hospital performance, literature review (other related framework), review of military hospital-related local documents, consultations with a national and sub-national expert. Finally, the Delphi technique used to finalize the framework.

Results
Based on the literature review results; 13 hospital Q&SAF were identified. After reviewing literature review results and expert opinions; Iran’s military hospitals Q&SAF was developed with 58 indictors in five dimensions including clinical effectiveness, safety, efficiency, patient-centeredness, and Responsive Management (Command and Control). The efficiency dimension had the highest number of indictors (19 indictors), whereas the patient-centered dimension had the lowest number of indices (4 indictors).

Conclusion
Regarding the comprehensiveness of the developed assessment framework due to its focus on the majority of quality dimensions and important components of the hospital’s performance, it can be used as a useful tool for assessing and continuously improving the quality of hospitals, particularly military hospitals.
Effect of the OPHN1 novel variant c.1025+1 G>A on RNA splicing: insights from a minigene assay
Authors: Yang Fei , Wang Minghui 
Published: July 2024

AbstractThis research analyzes the clinical data, whole-exome sequencing results, and in vitro minigene functional experiments of a child with developmental delay and intellectual disability. The male patient, aged 4, began experiencing epileptic seizures at 3 months post-birth and has shown developmental delay. Rehabilitation training was administered between the ages of one and two. There were no other significant family medical histories. Through comprehensive family exome genetic testing, a hemizygous variant in the 11th exon of the OPHN1 gene was identified in the affected child: c.1025 + 1G > A. Family segregation analysis confirmed the presence of this variant in the patient’s mother, which had not been previously reported. According to the ACMG guidelines, this variant was classified as a likely pathogenic variant. In response to this variant, an in vitro minigene functional experiment was designed and conducted, confirming that the mutation affects the normal splicing of the gene’s mRNA, resulting in a 56 bp retention on the left side of Intron 11. It was confirmed that OPHN1: c.1025 + 1G > A is the pathogenic cause of X-linked intellectual disabilities in the child, with clinical phenotypes including developmental delay and seizures.
Cardiac-derived extracellular vesicles improve mitochondrial function to protect the heart against ischemia/reperfusion injury by delivering ATP5a1
Authors: Liu Xuan , Meng Qingshu , Shi Shanshan , Geng Xuedi , Wang Enhao , Li Yinzhen , Lin Fang , Liang Xiaoting , Xi Xiaoling , Han Wei , Fan Huimin , Zhou Xiaohui 
Published: July 2024

AbstractBackgroundNumerous studies have confirmed the involvement of extracellular vesicles (EVs) in various physiological processes, including cellular death and tissue damage. Recently, we reported that EVs derived from ischemia-reperfusion heart exacerbate cardiac injury. However, the role of EVs from healthy heart tissue (heart-derived EVs, or cEVs) on myocardial ischemia-reperfusion (MI/R) injury remains unclear.ResultsHere, we demonstrated that intramyocardial administration of cEVs significantly enhanced cardiac function and reduced cardiac damage in murine MI/R injury models. cEVs treatment effectively inhibited ferroptosis and maintained mitochondrial homeostasis in cardiomyocytes subjected to ischemia-reperfusion injury. Further results revealed that cEVs can transfer ATP5a1 into cardiomyocytes, thereby suppressing mitochondrial ROS production, alleviating mitochondrial damage, and inhibiting cardiomyocyte ferroptosis. Knockdown of ATP5a1 abolished the protective effects of cEVs. Furthermore, we found that the majority of cEVs are derived from cardiomyocytes, and ATP5a1 in cEVs primarily originates from cardiomyocytes of the healthy murine heart. Moreover, we demonstrated that adipose-derived stem cells (ADSC)-derived EVs with ATP5a1 overexpression showed much better efficacy on the therapy of MI/R injury compared to control ADSC-derived EVs.ConclusionsThese findings emphasized the protective role of cEVs in cardiac injury and highlighted the therapeutic potential of targeting ATP5a1 as an important approach for managing myocardial damage induced by MI/R injury.
Manufacturing mesenchymal stromal cells in a microcarrier-microbioreactor platform can enhance cell yield and quality attributes: case study for acute respiratory distress syndrome
Authors: Krupczak Brandon , Farruggio Camille , Van Vliet Krystyn J. 
Published: July 2024

AbstractMesenchymal stem and stromal cells (MSCs) hold potential to treat a broad range of clinical indications, but clinical translation has been limited to date due in part to challenges with batch-to-batch reproducibility of potential critical quality attributes (pCQAs) that can predict potency/efficacy. Here, we designed and implemented a microcarrier-microbioreactor approach to cell therapy manufacturing, specific to anchorage-dependent cells such as MSCs. We sought to assess whether increased control of the biochemical and biophysical environment had the potential to create product with consistent presentation and elevated expression of pCQAs relative to established manufacturing approaches in tissue culture polystyrene (TCPS) flasks. First, we evaluated total cell yield harvested from dissolvable, gelatin microcarriers within a microbioreactor cassette (Mobius Breez) or a flask control with matched initial cell seeding density and culture duration. Next, we identified 24 genes implicated in a therapeutic role for a specific motivating indication, acute respiratory distress syndrome (ARDS); expression of these genes served as our pCQAs for initial in vitro evaluation of product potency. We evaluated mRNA expression for three distinct donors to assess inter-donor repeatability, as well as for one donor in three distinct batches to assess within-donor, inter-batch variability. Finally, we assessed gene expression at the protein level for a subset of the panel to confirm successful translation. Our results indicated that MSCs expanded with this microcarrier-microbioreactor approach exhibited reasonable donor-to-donor repeatability and reliable batch-to-batch reproducibility of pCQAs. Interestingly, the baseline conditions of this microcarrier-microbioreactor approach also significantly improved expression of several key pCQAs at the gene and protein expression levels and reduced total media consumption relative to TCPS culture. This proof-of-concept study illustrates key benefits of this approach to therapeutic cell process development for MSCs and other anchorage-dependent cells that are candidates for cell therapies.
Hypermethylated TAGMe as a universal-cancer-only methylation marker and its application in diagnosis and recurrence monitoring of urothelial carcinoma
Authors: Yang Zhicong , Chen Qing , Dong Shihua , Xu Peng , Zheng Wanxiang , Mao Zhanrui , Qian Chengchen , Zheng Xiangyi , Dai Lihe , Wang Chengyang , Shi Haoqing , Li Jing , Yuan Jianlin , Yu Wenqiang , Xu Chuanliang 
Published: July 2024

Abstract
Background
Urothelial carcinoma (UC) is the second most common urological malignancy. Despite numerous molecular markers have been evaluated during the past decades, no urothelial markers for diagnosis and recurrence monitoring have shown consistent clinical utility.

Methods
The methylation level of tissue samples from public database and clinical collected were analyzed. Patients with UC and benign diseases of the urinary system (BUD) were enrolled to establish TAGMe (TAG of Methylation) assessment in a training cohort (n = 567) using restriction enzyme-based bisulfite-free qPCR. The performance of TAGMe assessment was further verified in the validation cohort (n = 198). Urine samples from 57 UC patients undergoing postoperative surveillance were collected monthly for six months after surgery to assess the TAGMe methylation.

Results
We identified TAGMe as a potentially novel Universal-Cancer-Only Methylation (UCOM) marker was hypermethylated in multi-type cancers and investigated its application in UC. Restriction enzyme-based bisulfite-free qPCR was used for detection, and the results of which were consistent with gold standard pyrosequencing. Importantly, hypermethylated TAGMe showed excellent sensitivity of 88.9% (95% CI: 81.4–94.1%) and specificity of 90.0% (95% CI: 81.9–95.3%) in efficiently distinguishing UC from BUD patients in urine and also performed well in different clinical scenarios of UC. Moreover, the abnormality of TAGMe as an indicator of recurrence might precede clinical recurrence by three months to one year, which provided an invaluable time window for timely and effective intervention to prevent UC upstaging.

Conclusion
TAGMe assessment based on a novel single target in urine is effective and easy to perform in UC diagnosis and recurrence monitoring, which may reduce the burden of cystoscopy.
Trial registration ChiCTR2100052507. Registered on 30 October 2021
Association of early-term birth and breastfeeding practices with nutritional outcomes in singleton term infants: a multicenter cross-sectional study
Authors: Zhang Li , Liu Hui-Juan , Li Ping , Liu Yi , Zhang Ting , Zhu Jin-Yi , Zhu Hong-Mei , Zhou Ya-Ping , Wang Hai-Jun , Li Yan 
Published: July 2024

Abstract
Background
Limited research has explored the associations of gestational age (GA) and breastfeeding practices with growth and nutrition in term infants.

Methods
This multicenter cross-sectional study recruited 7299 singleton term infants from well-child visits in Shandong, China, between March 2021 and November 2022. Data on GA, gender, ethnicity, birth weight, parental heights, gestational diabetes and hypertension, age at visit, breastfeeding practices (point-in-time data at visit for infants < 6 months and retrospective data at 6 months for infants ≥ 6 months), complementary foods introduction, infant length and weight, were collected. 7270 infants were included in the analysis after excluding outliers with Z-scores of length (LAZ), weight or weight for length (WLZ) <-4 or > 4. Linear regression models adjused for covariates explored the impact of GA and breastfeeding practices on LAZ and WLZ, while logistic regression models evaluated their effect on the likelihood of moderate and severe stunting (MSS, LAZ<-2), moderate and severe acute malnutrition (MSAM, WLZ<-2) and overweight/obesity (WLZ > 2). Sensitivity analysis was conducted on normal birth weight infants (2.5–4.0 kg).

Results
Infants born early-term and exclusively breastfed accounted for 31.1% and 66.4% of the sample, respectively. Early-term birth related to higher WLZ (< 6 months: β = 0.23, 95% confidence interval (CI): 0.16, 0.29; ≥6 months: β = 0.12, 95% CI: 0.04, 0.20) and an increased risk of overweight/obesity throughout infancy (< 6 months: OR: 1.41, 95% CI 1.08, 1.84; ≥6 months: OR: 1.35, 95% CI 1.03, 1.79). Before 6 months, early-term birth correlated with lower LAZ (β=-0.16, 95% CI: -0.21, -0.11) and an increased risk of MSS (OR: 1.01, 95%CI 1.00, 1.02); Compared to exclusive breastfeeding, exclusive formula-feeding and mixed feeding linked to lower WLZ (β=-0.15, 95%CI -0.30, 0.00 and β=-0.12, 95%CI -0.19, -0.05, respectively) and increased risks of MSAM (OR: 5.57, 95%CI 1.95, 15.88 and OR: 3.19, 95%CI 1.64, 6.19, respectively). Sensitivity analyses confirmed these findings.

Conclusions
The findings emphasize the health risks of early-term birth and the protective effect of exclusive breastfeeding in singleton term infants, underscoring the avoidance of nonmedically indicated delivery before 39 weeks and promoting exclusive breastfeeding before 6 months.
Repetitive transcranial magnetic stimulation promotes motor function recovery in mice after spinal cord injury via regulation of the Cx43-autophagy loop
Authors: Zhang Lechi , Xiao Zhihang , Su Zelin , Wang Xinlong , Tian Huifang , Su Min 
Published: July 2024

AbstractSpinal cord injury (SCI) is a severe condition with an extremely high disability rate. It is mainly manifested as the loss of motor, sensory and autonomic nerve functions below the injury site. High-frequency transcranial magnetic stimulation, a recently developed neuromodulation method, can increase motor function in mice with spinal cord injury. This study aimed to explore the possible mechanism by which transcranial magnetic stimulation (TMS) restores motor function after SCI. A complete T8 transection model of the spinal cord was established in mice, and the mice were treated daily with 15 Hz high-frequency transcranial magnetic stimulation. The BMS was used to evaluate the motor function of the mice after SCI. Western blotting and immunofluorescence were used to detect the expression of Connexin43 (CX43) and autophagy-related proteins in vivo and in vitro, and correlation analysis was performed to study the relationships among autophagy, CX43 and motor function recovery after SCI in mice. Western blotting was used to observe the effect of magnetic stimulation on the expression of mTOR pathway members. In the control group, the expression of CX43 was significantly decreased, and the expression of microtubule-associated protein 1 A/1b light chain 3 (LC3II) and P62 was significantly increased after 4 weeks of spinal cord transection. After high-frequency magnetic stimulation, the level of CX43 decreased, and the levels of LC3II and P62 increased in primary astrocytes. The BMS of the magnetic stimulation group was greater than that of the control group. High-frequency magnetic stimulation can inhibit the expression of CX43, which negatively regulates autophagic flux. HF-rTMS increased the expression levels of mTOR, p-mTOR and p-S6. Our experiments showed that rTMS can restore hindlimb motor function in mice after spinal cord injury via regulation of the Cx43-autophagy loop and activation of the mTOR signalling pathway.
Emergence of Capnocytophaga canimorsus and Capnocytophaga cynodegmi in oral cavities of newborn puppies, a pilot study
Authors: Suominen Kristiina , Åvall-Jääskeläinen Silja , Sallinen Inka , Virtala Anna-Maija , Koort Joanna 
Published: July 2024

AbstractCapnocytophaga canimorsus and Capnocytophaga cynodegmi are commensal bacteria in the oral cavities of dogs. Both are zoonotic pathogens that could infect humans via dog bites. C. canimorsus may cause life-threatening infections in humans, whereas C. cynodegmi infections tend to be milder and more localized. Capsular serovars A–C of C. canimorsus seem to be virulence-associated. Some of the C. canimorsus serovars described to date can also be detected in other Capnocytophaga species, including C. cynodegmi. The objective of this pilot study was to investigate the emergence of C. canimorsus and C. cynodegmi after birth in oral cavities of puppies and to evaluate the impact of the dam’s Capnocytophaga spp. carrier status on the emergence. Ten litters, altogether 59 puppies, were included in the study. The puppies and their dams were sampled at five time points over seven weeks after whelping. Oral swab samples taken were investigated for the presence of C. canimorsus and C. cynodegmi by species-specific polymerase chain reaction (PCR), the specificity of which was verified by sequencing a selection of the PCR products. Samples that were positive in Capnocytophaga PCR reactions were also capsular-typed by PCR to gain more knowledge about the Capnocytophaga spp. present in the samples. Altogether 10.2% and 11.9% of puppies, or 20.0% and 30.0% of litters tested PCR-positive for C. canimorsus and C. cynodegmi, respectively. Capnocytophaga PCR-positive puppy samples were always positive for only C. cynodegmi or C. canimorsus, not both. Most Capnocytophaga PCR-positive puppies became positive at the age of 5 to 7 weeks. Only a minority (5/16) of the C. cynodegmi PCR-positive dog samples were positive in capsular typing PCR, whereas all C. canimorsus PCR-positive dog samples were negative in capsular typing PCR. For all Capnocytophaga PCR-positive puppies, their dam was positive for the same Capnocytophaga species. These results suggest that puppies become colonized by C. cynodegmi or C. canimorsus from their dams at the time of deciduous teeth eruption.
A prospective study of HER3 expression pre and post neoadjuvant therapy of different breast cancer subtypes: implications for HER3 imaging therapy guidance
Authors: Sinevici Nicoleta , Edmonds Christine E. , Dontchos Brian N. , Wang Gary , Lehman Constance D. , Isakoff Steven , Mahmood Umar 
Published: July 2024

Abstract
Purpose
HER3, a member of the EGFR receptor family, plays a central role in driving oncogenic cell proliferation in breast cancer. Novel HER3 therapeutics are showing promising results while recently developed HER3 PET imaging modalities aid in predicting and assessing early treatment response. However, baseline HER3 expression, as well as changes in expression while on neoadjuvant therapy, have not been well-characterized. We conducted a prospective clinical study, pre- and post-neoadjuvant/systemic therapy, in patients with newly diagnosed breast cancer to determine HER3 expression, and to identify possible resistance mechanisms maintained through the HER3 receptor.

Experimental design
The study was conducted between May 25, 2018 and October 12, 2019. Thirty-four patients with newly diagnosed breast cancer of any subtype (ER ± , PR ± , HER2 ±) were enrolled in the study. Two core biopsy specimens were obtained from each patient at the time of diagnosis. Four patients underwent a second research biopsy following initiation of neoadjuvant/systemic therapy or systemic therapy which we define as neoadjuvant therapy. Molecular characterization of HER3 and downstream signaling nodes of the PI3K/AKT and MAPK pathways pre- and post-initiation of therapy was performed. Transcriptional validation of finings was performed in an external dataset (GSE122630).

Results
Variable baseline HER3 expression was found in newly diagnosed breast cancer and correlated positively with pAKT across subtypes (r = 0.45). In patients receiving neoadjuvant/systemic therapy, changes in HER3 expression were variable. In a hormone receptor-positive (ER +/PR +/HER2-) patient, there was a statistically significant increase in HER3 expression post neoadjuvant therapy, while there was no significant change in HER3 expression in a ER +/PR +/HER2+ patient. However, both of these patients showed increased downstream signaling in the PI3K/AKT pathway. One subject with ER +/PR −/HER2− breast cancer and another subject with ER +/PR +/HER2 + breast cancer showed decreased HER3 expression. Transcriptomic findings, revealed an immune suppressive environment in patients with decreased HER3 expression post therapy.

Conclusion
This study demonstrates variable HER3 expression across breast cancer subtypes. HER3 expression can be assessed early, post-neoadjuvant therapy, providing valuable insight into cancer biology and potentially serving as a prognostic biomarker. Clinical translation of neoadjuvant therapy assessment can be achieved using HER3 PET imaging, offering real-time information on tumor biology and guiding personalized treatment for breast cancer patients.
Effect of testosterone therapy on breast tissue composition and mammographic breast density in trans masculine individuals
Authors: Heng Yujing J. , Baker Gabrielle M. , Fein-Zachary Valerie J. , Guzman-Arocho Yaileen D. , Bret-Mounet Vanessa C. , Massicott Erica S. , Torous Vanda F. , Schnitt Stuart J. , Gitin Sy , Russo Paul , Tobias Adam M. , Bartlett Richard A. , Varma Gopal , Kontos Despina , Yaghjyan Lusine , Irwig Michael S. , Potter Jennifer E. , Wulf Gerburg M. 
Published: July 2024

Abstract
Background
The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs).

Methods
Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted.

Results
Longer duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(β) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(β) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(β) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(β) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(β) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist’s breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05).

Conclusions
TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk.