bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosome lncRNA IFNG-AS1 derived from mesenchymal stem cells of human adipose ameliorates neurogenesis and ASD-like behavior in BTBR mice
Authors: Fu Yu , Zhang Yuan-lin , Liu Rong-qi , Xu Meng-meng , Xie Jun-ling , Zhang Xing-liao , Xie Guang-ming , Han Yao-ting , Zhang Xin-Min , Zhang Wan-ting , Zhang Jing , Zhang Jun 
Published: February 2024

Abstract
Background
The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear.

Results
The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis.

Conclusion
We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD.

Graphical Abstract
Strategies for engaging older adults and informal caregivers in health policy development: A scoping review
Authors: Kolade Opeyemi Rashidat , Porat-Dahlerbruch Joshua , Makhmutov Rustem , van Achterberg Theo , Ellen Moriah Esther 
Published: February 2024

Abstract
Background
Care for older adults is high on the global policy agenda. Active involvement of older adults and their informal caregivers in policy-making can lead to cost–effective health and long-term care interventions. Yet, approaches for their involvement in health policy development have yet to be extensively explored. This review maps the literature on strategies for older adults (65+ years) and informal caregivers’ involvement in health policy development.

Method
As part of the European Union TRANS-SENIOR program, a scoping review was conducted using the Joanna Briggs Institute’s methodology. Published and grey literature was searched, and eligible studies were screened. Data were extracted from included studies and analysed using the Multidimensional Framework for Patient and Family Engagement in Health and Healthcare.

Results
A total of 13 engagement strategies were identified from 11 publications meeting the inclusion criteria. They were categorized as “traditional”, “deliberative” and “others”, adopting the World Bank’s categorization of engagement methods. Older adults and informal caregivers are often consulted to elicit opinions and identify priorities. However, their involvement in policy formulation, implementation and evaluation is unclear from the available literature. Findings indicate that older adults and their informal caregivers do not often have equal influence and shared leadership in policy-making.

Conclusion
Although approaches for involving older adults and their informal caregivers’ involvement were synthesized from literature, we found next to no information about their involvement in policy formulation, implementation and evaluation. Findings will guide future research in addressing identified gaps and guide policy-makers in identifying and incorporating engagement strategies to support evidence-informed policy-making processes that can improve health outcomes for older adults/informal caregivers.
DeepRisk network: an AI-based tool for digital pathology signature and treatment responsiveness of gastric cancer using whole-slide images
Authors: Tian Mengxin , Yao Zhao , Zhou Yufu , Gan Qiangjun , Wang Leihao , Lu Hongwei , Wang Siyuan , Zhou Peng , Dai Zhiqiang , Zhang Sijia , Sun Yihong , Tang Zhaoqing , Yu Jinhua , Wang Xuefei 
Published: February 2024

Abstract
Background
Digital histopathology provides valuable information for clinical decision-making. We hypothesized that a deep risk network (DeepRisk) based on digital pathology signature (DPS) derived from whole-slide images could improve the prognostic value of the tumor, node, and metastasis (TNM) staging system and offer chemotherapeutic benefits for gastric cancer (GC).

Methods
DeepRisk is a multi-scale, attention-based learning model developed on 1120 GCs in the Zhongshan dataset and validated with two external datasets. Then, we assessed its association with prognosis and treatment response. The multi-omics analysis and multiplex Immunohistochemistry were conducted to evaluate the potential pathogenesis and spatial immune contexture underlying DPS.

Results
Multivariate analysis indicated that the DPS was an independent prognosticator with a better C-index (0.84 for overall survival and 0.71 for disease-free survival). Patients with low-DPS after neoadjuvant chemotherapy responded favorably to treatment. Spatial analysis indicated that exhausted immune clusters and increased infiltration of CD11b+CD11c+ immune cells were present at the invasive margin of high-DPS group. Multi-omics data from the Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD) hint at the relevance of DPS to myeloid derived suppressor cells infiltration and immune suppression.

Conclusion
DeepRisk network is a reliable tool that enhances prognostic value of TNM staging and aid in precise treatment, providing insights into the underlying pathogenic mechanisms.
Expanding the reach of commercial cell therapies requires changes at medical centers
Authors: Stroncek David F. , Zhang Nan , Ren Jiaqiang , Somerville Rob , Dinh Anh 
Published: February 2024

AbstractThe clinical application of cell therapies is becoming increasingly important for the treatment of cancer, congenital immune deficiencies, and hemoglobinopathies. These therapies have been primarily manufactured and used at academic medical centers. However, cell therapies are now increasingly being produced in centralized manufacturing facilities and shipped to medical centers for administration. Typically, these cell therapies are produced from a patient’s own cells, which are the critical starting material. For these therapies to achieve their full potential, more medical centers must develop the infrastructure to collect, label, cryopreserve, test, and ship these cells to the centralized laboratories where these cell therapies are manufactured. Medical centers must also develop systems to receive, store, and infuse the finished cell therapy products. Since most cell therapies are cryopreserved for shipment and storage, medical centers using these therapies will require access to liquid nitrogen product storage tanks and develop procedures to thaw cell therapies. These services could be provided by the hospital pharmacy or transfusion service, but the latter is likely most appropriate. Another barrier to implementing these services is the variability among providers of these cell therapies in the processes related to handling cell therapies. The provision of these services by medical centers would be facilitated by establishing a national coordinating center and a network of apheresis centers to collect and cryopreserve the cells needed to begin the manufacturing process and cell therapy laboratories to store and issue the cells. In addition to organizing cell collections, the coordinating center could establish uniform practices for collecting, labeling, shipping, receiving, thawing, and infusing the cell therapy.
Exploring the interplay of gut microbiota, inflammation, and LDL-cholesterol: a multiomics Mendelian randomization analysis of their causal relationship in acute pancreatitis and non-alcoholic fatty liver disease
Authors: Yan Congzhi , Bao Jingxia , Jin Jinji 
Published: February 2024

Abstract
Background
Acute pancreatitis and non-alcoholic fatty liver disease are both serious diseases in the digestive system. The pathogenesis of both diseases is extremely complex closely and it related to gut microbiota, inflammation, and blood fat. There is a close relationship between gut microbiota and blood lipids.

Methods
In this study, we used three types of exposure: 412 gut microbiota, 731 inflammatory cells, and 91 inflammatory proteins (pqtls), with LDL-C as an intermediary and acute pancreatitis and non-alcoholic fatty liver disease as outcomes. We mainly used MR-IVW, co-localization analysis, and reverse MR analysis methods for analysis.

Results
7 gut microbiota, 21 inflammatory cells, and 3 inflammatory proteins can affect LDL-C levels. LDL-C is associated with acute pancreatitis and non-alcoholic fatty liver disease.

Conclusions
Three omics were used: 412 gut microbiota, 731 inflammatory cells, and 91 inflammatory proteins (pqtls). It explains the causal relationship between multiomics, LDL- cholesterol, acute pancreatitis, and non-alcoholic fatty liver disease.
The insular cortex is not insular in thyroid eye disease: neuroimaging revelations of central–peripheral system interaction
Authors: Zhang Haiyang , Liu Yuting , Xia Duojin , Jiang Mengda , Li Yinwei , Sun Jing , Guan Haixia , Zhu Ling , Song Xuefei , Wang Jue , Fan Xianqun , Zhou Huifang 
Published: February 2024

Abstract
Background
Thyroid eye disease (TED) is highly correlated with dysregulated immunoendocrine status. The insular cortex was found to regulate peripheral inflammation and immunomodulation in mice. This study aimed to explore whether the insular cortex in patients with TED played a modulatory role including the aberrant brain functional alteration and its association with immunoendocrine status.

Methods
This study included 34 active patients (AP), 30 inactive patients (IP) with TED, and 45 healthy controls (HC) matched for age, sex, and educational level. Comprehensive clinical details (especially immunoendocrine markers) and resting-state functional magnetic resonance imaging data were collected from each participant. The amplitude of low-frequency fluctuation (ALFF) was used to probe the aberrant alterations of local neural activity. The seed-based functional connectivity (FC) analysis was used to explore the relationship between the insular cortex and each voxel throughout the whole brain. The correlation analysis was conducted to assess the association between insular neurobiomarkers and immunoendocrine parameters.

Results
When compared with the IP and HC groups, the AP group displayed significantly higher ALFF values in the right insular cortex (INS.R) and lower FC values between the INS.R and the bilateral cerebellum. None of the neurobiomarkers differed between the IP and HC groups. Besides, correlations between insular neurobiomarkers and immunoendocrine markers (free thyroxine, the proportion of T cells, and natural killer cells) were identified in both AP and IP groups.

Conclusions
This study was novel in reporting that the dysregulation of the insular cortex activity in TED was associated with abnormal peripheral immunoendocrine status. The insular cortex might play a key role in central–peripheral system interaction in TED. Further research is crucial to enhance our understanding of the central–peripheral system interaction mechanisms involved in autoimmune diseases.
Three-dimensional computed tomography analysis of airway volume in growing class II patients treated with Frankel II appliance
Authors: Ahmed Marwa Jameel , Diar-Bakirly Samira , Deirs Nelson , Hassan Amar , Ghoneima Ahmed 
Published: February 2024

Abstract
Objective
The purpose of this retrospective study was to assess the airway volume changes associated with the use of Frankel appliance (FR II) in Class II malocclusion patients using three-dimensional cone beam computed tomography (3D CBCT) imaging.

Materials and methods
The sample consisted of 31 Class II malocclusion patients (mean age 9.24 ± 1.93 years old, 17 males (54.8%) and 14 females (45.2%)) treated with FR II appliance by the same orthodontist for an average of 9 months ± 20 days. CBCT images were taken before and after treatment and upper airway volume changes were measured using Dolphin 3D software version11.0 (Dolphin Imaging, Chatsworth, CA) and statistically compared.

Results
Airway volume of nasal cavity, nasopharynx, oropharynx, hypopharynx and the total airway volume significantly increased after the use of FR II appliance. In addition, significant increase was reported in maxillary base, inter-molar, inter-premolar and inter-canine width. Significant increase in soft tissue thickness was only recorded opposite to CV2.

Conclusion
The use of the FR II appliance in growing subjects with Class II malocclusion led to a significant increase in the upper airway volume in addition to the anticipated dental and skeletal transverse expansion effects.
Intraoperative femurofibular angle combined with tibiofibular angle measurement has fewer correction errors in open-wedge high tibial osteotomy
Authors: Zhao Chen , Zhang Bing , Liu Xuejiao , Li Bo , Bao Liang , Liu Cong , Fan Lihong 
Published: February 2024

Abstract
Aim
This study aimed to verify the accuracy of intraoperative femurofibular angle combined with tibiofibular angle (FFA–TFA) measurement and compare it with traditional alignment line methods in open-wedge high tibial osteotomy (OWHTO).

Methods
A total of 174 knees of 122 patients undergoing OWHTO and using an alignment line or FFA–TFA measurement as an index of optimal correction were included in this retrospective study. The intraoperative alignment line passed through the targeted weight-bearing line (WBL) of the tibial plateau in the alignment line group. The intraoperative FFA–TFA aligned to the preplanned FFA–TFA angle in the FFA–TFA group. WBL, FFA, TFA, and knee joint-line convergence angle of the femur and tibia were assessed as radiological results preoperatively and one year after surgery. The Knee Society Score and the Western Ontario and McMaster Universities were assessed as objective clinical results.

Results
Postoperative WBL in the FFA–TFA group was closer to the target WBL than in the alignment line group (FFA–TFA vs alignment line group: 1.43 ± 1.20% vs 3.82 ± 3.29%; P < 0.001). The FFA–TFA group had fewer over-correction and under-correction rates than the alignment line group (28.7% and 12.6% vs 11.5% and 3.40%; P < 0.001). No significant differences were observed in the clinical results between the two groups one year after surgery (P > 0.05).

Conclusions
The intraoperative measurement of FFA–TFA had fewer complications in terms of under-correction and over-correction compared with the alignment line measurement. No significant differences between the two methods were observed in clinical results one year after surgery.
Moderating effect of work fatigue on the association between resilience and posttraumatic stress symptoms: a cross-sectional multi-country study among pharmacists during the COVID-19 pandemic
Authors: Younes Samar , Hallit Souheil , Mohammed Irfan , El Khatib Sarah , Brytek-Matera Anna , Eze Shadrach Chinecherem , Egwu Kenneth , Jabeen Rawshan , Pavlović Nebojša , Salameh Pascale , Cherfane Michelle , Akel Marwan , Haddad Chadia , Choueiry Randa , Fekih-Romdhane Feten , Iskandar Katia 
Published: February 2024

Abstract
Introduction
In the context of the COVID-19 pandemic, pharmacists, despite their vital contributions, have faced significant challenges that have impacted their mental well-being, potentially leading to the development of Post-Traumatic Stress symptoms (PTSS). The aim of this study was to investigate the role of work-related fatigue as a potential moderator in the relationship between pharmacists’ resilience and their likelihood of experiencing PTSS during the COVID-19 pandemic.

Methods
A cross-sectional survey was conducted online in eight countries from January to December 2021, including Brazil, Lebanon, Nigeria, Pakistan, Poland, Serbia, and Tunisia. The mediation analysis was conducted using PROCESS MACRO (an SPSS add-on) v3.4 model 1, taking work fatigue as a moderator in the association between resilience and PTSS.

Results
A total of 442 pharmacists were enrolled in this study (mean age = 33.91 ± 10.36 years) with 59.5% of them being females. The results were adjusted over country, gender, working in contact with COVID-19, working patients, working mandatory hours, working voluntary hours, age, household crowding index and number of months engaged in COVID-19. The interactions resilience by physical (Beta = 0.02; p = .029), mental (Beta = 0.02; p = .040) and emotional (Beta = 0.03; p = .008) work fatigue were significantly associated with PTSS; for pharmacists with low to moderate levels of physical (Beta = − 0.33; p < .001 and Beta = − 0.21; p = .001), mental (Beta = − 0.29; p < .001 and Beta = − 0.18; p = .006) and emotional (Beta = − 0.31; p < .001 and Beta = − 0.17; p = .008) work fatigue, higher resilience was significantly related to lower PTSS levels. However, for pharmacists with high levels of physical/mental/emotional work fatigue, the association between resilience and PTSS became non-significant.

Conclusion
This study highlights the complex relationship between work-related fatigue, resilience, and PTSS in pharmacists. It emphasizes the need to address work-related fatigue for pharmacists’ psychological well-being during crises, offering insights for tailored support and interventions.
Metformin versus metformin plus pioglitazone on gonadal and metabolic profiles in normal-weight women with polycystic ovary syndrome: a single-center, open-labeled prospective randomized controlled trial
Authors: Zhao Han , Zhang Jiaqi , Xing Chuan , Cheng Xiangyi , He Bing 
Published: February 2024

Abstract
Objective
To investigate the effects of metformin (MET) monotherapy and pioglitazone plus MET (PIOMET) therapy on gonadal and metabolic profiles in normal-weight women with polycystic ovary syndrome (PCOS).

Methods
Sixty normal-weight women with PCOS were recruited between January and September 2022 at the Shengjing Hospital of China Medical University. They were randomly assigned to the MET or PIOMET groups for 12 weeks of MET monotherapy or PIOMET therapy. Anthropometric measurements, menstrual cycle changes, gonadal profiles, and the oral glucose insulin-releasing test (OGIRT) were performed at baseline and after the 12-week treatment.

Results
Thirty-six participants completed the trial. MET and PIOMET therapies improved menstrual cycles after the 4- and 12-week treatments; however, there was no statistical difference between the two groups. PIOMET therapy improved luteinizing hormone (LH), luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, and free androgen index (FAI) levels after the 4-week treatment, whereas MET monotherapy only improved total testosterone (TT) levels compared to baseline (P < 0.05). Both MET and PIOMET therapies improved TT and anti-Mullerian hormone (AMH) levels after the 12-week treatment (P < 0.05). In addition, only PIOMET therapy significantly improved sex hormone-binding globulin (SHBG), FAI, and androstenedione (AND) levels than the baseline (P < 0.05). PIOMET therapy improved SHBG and AMH levels more effectively than MET monotherapy (P < 0.05). Furthermore, PIOMET treatment was more effective in improving blood glucose levels at 120 and 180 min of OGIRT compared to MET monotherapy (P < 0.05).

Conclusions
In normal-weight women with PCOS, PIOMET treatment may have more benefits in improving SHBG, AMH, and postprandial glucose levels than MET monotherapy, and did not affect weight. However, the study findings need to be confirmed in PCOS study populations with larger sample sizes.
Arachidonic acid inhibit granulosa cell function by affecting metabolic function of liver in brown adipose transplantation rats
Authors: Yan Yan , Di Fangfang , Zhang Ruoxi , Song Liwen , Zhang Runjie , Qiu Jin 
Published: February 2024

Abstract
Background
Polycystic ovary syndrome (PCOS) is a gynecological endocrine disease and could be considered a metabolic disease because it is often accompanied by obesity and insulin resistance. Brown adipose tissue (BAT) transplantation has been shown to be effective in treating PCOS rats.

Results
The study demonstrated that BAT successfully recovered the reproductive and metabolic phenotype of PCOS rats. The disorder estrous cycle, abnormal hyperglycemia and the expression of liver factors were improved. Differentially expressed metabolites were analyzed, among them, arachidonic acid may play a role in inhibiting cell proliferation, enhancing oxidative stress reaction, promoting estrogen expression, and reducing progesterone level in KGN cells.

Conclusion
Our findings suggest that BAT transplantation may be a therapeutic strategy for PCOS by changing the expression of some cytokines and metabolites. Differentially expressed metabolites might be crucially important for the pathogenesis of PCOS.