bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ameliorative role of specific probiotic combinations on bone loss in the ovariectomized rat model
Authors: Gholami Ahmad , Dabbaghmanesh Mohammad Hossein , Ghasemi Younes , Koohpeyma Farhad , Talezadeh Pedram , Montazeri-Najafabady Nima 
Published: September 2022

Abstract
Background
Osteoporosis, a skeletal disease described by impaired bone strength, cause an increased risk of fractures. We aimed in this study to clarify which particular wise combination of probiotics has the most beneficial effect in the rat model of osteoporosis.

Methods
Sixty-three mature female Sprague Dawley rats (12–14 weeks old, weight 200 ± 20 g) were ovariectomized and then divided into nine random groups, each group consisting of 7 rats. Lactic acid bacteria were isolated from traditional fermented yogurt on the northern coast of the Persian Gulf. Seven combinations of probiotics, each containing three probiotic strains, were designed and administered (1 × 10 9 CFU / ml/strain daily along with their water) to treat ovariectomized rats. The period from ovariectomy to eutanásia was 3 months. For evaluating femur, spine, and tibia, bone mineral density (BMD), and bone mineral content (BMC), Dual-energy X-ray absorptiometry (DEXA) scans were performed. Also, effect of probiotic combinations was assessed on biochemical markers including vitamin D, calcium, phosphorus, and alkaline phosphatase in serum.

Results
Combination NO 4, containing L. acidophilus, B. longum, and L. reuteri, is the most influential group on global, spine, and femur BMD. Combination NO 3, containing L. acidophilus, L. casei, and L. reuteri, also significantly affects the BMD of the tibia among the treatment group. We found that the combination NO 4 had the most significant ameliorative effect on global BMC. Also, combination NO 1 (comprising L. acidophilus, L. casei, and B. longum), NO 6 (containing L. casei, B. longum, and Bacillus coagulans), NO 7 (containing L. casei, L. reuteri, and B. longum), and NO 4 had the most considerable raising effect on spine BMC. In addition, the serum calcium and Vitamin D concentration in the groups NO 4, 6, and 7 were significantly higher than in OVX groups, whereas the alkaline phosphatase concentration was considerably reduced in these groups.

Conclusion
Among nine effective probiotics, a combination containing L. acidophilus, B. longum, and L. reuteri is the most influential group in ovariectomized osteoporotic rat.
Effectiveness of an online module: climate-change and sustainability in clinical practice
Authors: Dunne H. , Rizan C. , Jones A. , Bhutta M. F. , Taylor T. , Barna S. , Taylor C. J. , Okorie M. 
Published: September 2022

Abstract
Background
Climate change has significant implications for health, yet healthcare provision itself contributes significant greenhouse gas emission. Medical students need to be prepared to address impacts of the changing environment and fulfil a key role in climate mitigation. Here we evaluate the effectiveness of an online module on climate-change and sustainability in clinical practice designed to achieve learning objectives adapted from previously established sustainable healthcare priority learning outcomes.

Methods
A multi-media, online module was developed, and 3rd and 4th year medical students at Brighton and Sussex Medical School were invited to enrol. Students completed pre- and post-module questionnaires consisting of Likert scale and white space answer questions. Quantitative and qualitative analysis of responses was performed.

Results
Forty students enrolled and 33 students completed the module (83% completion rate). There was a significant increase in reported understanding of key concepts related to climate change and sustainability in clinical practice (p < 0.001), with proportion of students indicating good or excellent understanding increasing from between 2 – 21% students to between 91 – 97% students. The majority (97%) of students completed the module within 90 min. All students reported the module was relevant to their training. Thematic analysis of white space responses found students commonly reported they wanted access to more resources related to health and healthcare sustainability, as well as further guidance on how to make practical steps towards reducing the environmental impact within a clinical setting.

Conclusion
This is the first study to evaluate learner outcomes of an online module in the field of sustainable health and healthcare. Our results suggest that completion of the module was associated with significant improvement in self-assessed knowledge of key concepts in climate health and sustainability. We hope this approach is followed elsewhere to prepare healthcare staff for impacts of climate change and to support improving the environmental sustainability of healthcare delivery.

Trial registration
Study registered with Brighton and Sussex Medical School Research Governance and Ethics Committee (BSMS RGEC). Reference: ER/BSMS3576/8, Date: 4/3/2020.
Mitigating urinary incontinence condition using machine learning
Authors: Ali Haneen , Ahmed Abdulaziz , Olivos Carlos , Khamis Khaled , Liu Jia 
Published: September 2022

Abstract
Background
Urinary incontinence (UI) is the inability to completely control the process of releasing urine. UI presents a social, medical, and mental issue with financial consequences.

Objective
This paper proposes a framework based on machine learning for predicting urination time, which can benefit people with various degrees of UI.

Method
A total of 850 data points were self-recorded by 51 participants to investigate how different factors impact urination time. The participants were instructed to record input data (such as the time of consumption and the number of drinks) and output data (i.e., the time the individual urinated). Other factors, such as age and BMI, were also considered. The study was conducted in two phases: (1) data was prepared for modeling, including missing values, data encoding, and scaling; and (2) a classification model was designed with four output classes of the next urination time: <  = 30 min, 31–60 min, 61–90 min, > 90 min. The model was built in two steps: (1) feature selection and (2) model training and testing. Feature selection methods such as lasso regression, decision tree, random forest, and chi-square were used to select the best features, which were then used to train an extreme gradient boosting (XGB) algorithm model to predict the class of the next urination time.

Result
The feature selection steps resulted in nine features considered the most important features affecting UI. The accuracy, precision, recall, and F1 score of the XGB predictive model are 0.70, 0.73, 0.70, and 0.71, respectively.

Conclusion
This research is the first step in developing a machine learning model to predict when a person will need to urinate. A precise predictive instrument can enable healthcare providers and caregivers to assist people with various forms of UI in reliable, prompted voiding. The insights from this predictive model can allow future apps to go beyond current UI-related apps by predicting the time of urination using the most relevant factors that impact voiding frequency.
The relative impact of underweight, overweight, smoking, and physical inactivity on health and associated costs in Indonesia: propensity score matching of a national sample
Authors: Ihyauddin Zulfikar , Marthias Tiara , Anindya Kanya , Ng Nawi , Dewi Fatwa Sari Tetra , Hulse Emily S. G. , Aji Reza Pandu , Putri Dwi Astuti Dharma , Lee John Tayu 
Published: September 2022

Abstract
Background
Indonesia is in the middle of a rapid epidemiological transition with an ageing population and increasing exposure to risk factors for chronic conditions. This study examines the relative impacts of obesity, tobacco consumption, and physical inactivity, on non-communicable diseases multimorbidity, health service use, catastrophic health expenditure (CHE), and loss in employment productivity in Indonesia.

Methods
Secondary analyses were conducted of cross-sectional data from adults aged ≥ 40 years (n = 12,081) in the Indonesian Family Life Survey 2014/2015. We used propensity score matching to assess the associations between behavioural risk factors and health service use, CHE, employment productivity, and multimorbidity.

Results
Being obese, overweight and a former tobacco user was associated with a higher number of chronic conditions and multimorbidity (p < 0.05). Being a former tobacco user contributed to a higher number of outpatient and inpatient visits as well as CHE incidences and work absenteeism. Physical inactivity relatively increased the number of outpatient visits (30% increase, p < 0.05) and work absenteeism (21% increase, P < 0.06). Although being underweight was associated with an increased outpatient care utilisation (23% increase, p < 0.05), being overweight was negatively associated with CHE incidences (50% decrease, p < 0.05).

Conclusion
Combined together, obesity, overweight, physical inactivity and tobacco use contributed to an increased number of NCDs as well as medical costs and productivity loss in Indonesia. Interventions addressing physical and behavioural risk factors are likely to have substantial benefits for individuals and the wider society in Indonesia.
Cross-sectorial collaboration on policy-driven rehabilitation care models for persons with neuromuscular diseases: reflections and behavior of community-based health professionals
Authors: Handberg Charlotte , Werlauff Ulla 
Published: September 2022

Abstract
Background
Persons with neuromuscular diseases (NMDs) often experience complex rehabilitation needs due to the disease’s impact on their functioning and progression of their diseases. As a consequence of legislation and “policy power”, community-based health professionals function as gatekeepers to the rehabilitation trajectory for persons with NMDs in a field where the other professionals are the specialists.

Aim
To investigate community-based health professionals’ reflections on and behaviors regarding collaboration with a tertiary rehabilitation hospital in a cross-sectorial rehabilitation care model with the overall aim of providing high quality rehabilitation for persons with NMD.

Methods
The design is qualitative and uses interpretive description methodology and the theoretical lens of Edgar Schein’s three levels of organizational culture and leadership.
An ethnographic fieldwork was conducted from September 1, 2019 to January 30, 2020. Eighty-four community-based health professionals were included and 17 of them were interviewed in four semi-structured focus group interviews (n = 10) and seven individual interviews (n = 7). In addition, 151 pages of observation data were generated. The study adheres to the COREQ guidelines.

Results
The analysis showed three themes of importance for the collaboration: Policy and legislation navigation represented that collaboration on rehabilitation was affected by legislation as a management tool with “the case” as the core element, and goal dilemmas. Cross-sectorial knowledge exchange promoted collaboration on coordinated and facilitated rehabilitation and knowledge sharing as a firm anchoring. Patient ownership negotiations implied collaboration was influenced by knowledge founded power and gatekeeping as a navigation tool.

Conclusion
Three levels of organizational culture and leadership were identified, and this overall structure guided the community-based health professionals in their work and in the complex organizational landscape of collaboration between disconnected healthcare systems. The findings provided insight into behavior and attitudes and the content and the values held by the professionals collaborating across sectors. Future collaboration in rehabilitation models should be multiprofessional and team based. The findings emphasize that it is imperative that managements and professionals strive to strengthen the structure of the collaborative team spirit because this will ensure well-planned, coordinated, and conducted rehabilitation for persons with NMD and enable and support future cross-sectorial collaboration in this rehabilitation model for these persons.
A novel nonsense variant (c.1499C>G) in CRB1 caused Leber congenital amaurosis-8 in a Chinese family and a literature review
Authors: Duan Wenhua , Zhou Taicheng , Jiang Huawei , Zhang Minhui , Hu Min , Zhang Liwei 
Published: September 2022

Abstract
Background
Leber’s congenital amaurosis (LCA) is a severe hereditary retinopathy disease that is characterized by early and severe reduction of vision, nystagmus, and sluggish or absent pupillary responses. To date, the pathogenesis of LCA remains unclear, and the majority of cases are caused by autosomal recessive inheritance. In this study, we explored the variant in the Crumbs homologue 1 (CRB1) gene in a Chinese family with LCA.

Methods
We conducted comprehensive ocular examinations and collected 5 ml of blood samples from members of a Chinese family with LCA. A pathogenic variant was identified by capturing (the panel in NGS) and Sanger sequencing validation.

Results
A nonsense variant (c.1499C>G) in the 6th exon of CRB1 gene in a Chinese family with LCA was identified, which predicted a change in the protein p. S500*, may lead to loss of gene function. We summarized the 76 variants reported thus far in CRB1 that caused LCA8.

Conclusions
This study reported a novel variant c.1499C>G (p. S500*) of the CRB1 gene occurred in a Chinese family with LCA, thus expanding the spectrum of CRB1 variants causing LCA.
Ligands stimulating antitumour immunity as the next G-quadruplex challenge
Authors: Miglietta Giulia , Marinello Jessica , Russo Marco , Capranico Giovanni 
Published: September 2022

AbstractG-quadruplex (G4) binders have been investigated to discover new anticancer drugs worldwide in past decades. As these ligands are generally not highly cytotoxic, the discovery rational was mainly based on increasing the cell-killing potency. Nevertheless, no G4 binder has been shown yet to be effective in cancer patients. Here, G4 binder activity at low dosages will be discussed as a critical feature to discover ligands with therapeutic effects in cancer patients. Specific effects of G4 binders al low doses have been reported to occur in cancer and normal cells. Among them, genome instability and the stimulation of cytoplasmic processes related to autophagy and innate immune response open to the use of G4 binders as immune-stimulating agents. Thus, we propose a new rational of drug discovery, which is not based on cytotoxic potency but rather on immune gene activation at non-cytotoxic dosage.
Genetic targeting or pharmacological inhibition of galectin-3 dampens microglia reactivity and delays retinal degeneration
Authors: Tabel Mona , Wolf Anne , Szczepan Manon , Xu Heping , Jägle Herbert , Moehle Christoph , Chen Mei , Langmann Thomas 
Published: September 2022

Abstract
Background
Dysfunctional humoral and cellular innate immunity are key components in the development and progression of age-related macular degeneration (AMD). Specifically, chronically activated microglia and their disturbed regulatory system contribute to retinal degeneration. Galectin-3, a β-galactose binding protein, is a potent driver of macrophage and microglia activation and has been implicated in neuroinflammation, including neurodegenerative diseases of the brain. Here, we hypothesized that genetic deficiency of galectin-3 or its modulation via TD139 dampens mononuclear phagocyte reactivity and delays retinal degeneration.

Methods
Galectin-3 expression in AMD patients was analyzed by immunohistochemical stainings. Galectin-3 knockout and BALB/cJ mice were exposed to white bright light with an intensity of 15,000 lux for 1 h and Cx3cr1GFP/+ mice to focal blue light of 50,000 lux for 10 min. BALB/cJ and Cx3cr1GFP/+ mice received intraperitoneal injections of 15 mg/kg TD139 or vehicle for five consecutive days, starting one day prior to light exposure. The effects of galectin-3 deficiency or inhibition on microglia were analyzed by immunohistochemical stainings and in situ hybridization of retinal sections and flat mounts. Pro-inflammatory cytokine levels in the retina and retinal pigment epithelium (RPE) were quantified by qRT-PCR and transcriptomic changes were analyzed by RNA-sequencing. Retinal thickness and structure were evaluated by optical coherence tomography.

Results
We found that galectin-3 expression was strongly upregulated in reactive retinal mononuclear phagocytes of AMD patients and in the two related mouse models of light-induced retinal degeneration. The experimental in vivo data further showed that specific targeting of galectin-3 by genetic knockout or administration of the small-molecule inhibitor TD139 reduced microglia reactivity and delayed retinal damage in both light damage conditions.

Conclusion
This study defines galectin-3 as a potent driver of retinal degeneration and highlights the protein as a drug target for ocular immunomodulatory therapies.
Ultrasensitive and visual detection of human norovirus genotype GII.4 or GII.17 using CRISPR-Cas12a assay
Authors: Qian Weidong , Huang Jie , Wang Ting , Fan Cheng , Kang Jie , Zhang Qian , Li Yongdong , Chen Si 
Published: September 2022

Abstract
Background
Integrating CRISPR-Cas12a sensors with isothermal signal amplification can be exploited to develop low-cost, disposable, and ultrasensitive assays for the diagnostics of human pathogens.

Methods
RT-RAA-Cas12a-mediated real-time or end-point fluorescent and lateral flow strip (LFS) assays for direct detection of norovirus (NOV) genotype GII.4 or GII.17 were explored.

Results
The results showed that our RT-RAA-Cas12a-mediated fluorescent and LFS assay could detect NOV GII.4 or GII.17 by targeting the viral protein 1 gene. Our RT-RAA-Cas12a-mediated fluorescent and LFS assay can specifically detect NOV GII.4 or GII.17 with no cross-reactivity for other related viruses. The low limit of detection could reach 0.1 copies/μL within approximately 30–40 min, and the results were visualized using an ultraviolet light illuminator or on a LFS without complex equipment. In addition, our RT-RAA-Cas12a-mediated fluorescent and LFS assay provided a visual and faster alternative to real-time RT-PCR assay, with 95.7% and 94.3% positive predictive agreement and 100% negative predictive agreement.

Conclusions
Together, our RT-RAA-Cas12a-mediated approach would have a great potential for point-of-care diagnostics of NOV GII.4 and/or GII.17 in resource-limited settings.
Identification and in silico analysis of a spectrum of SLC4A11 variations in Indian familial and sporadic cases of congenital hereditary endothelial dystrophy
Authors: Salman Mohd , Verma Anshuman , Chaurasia Sunita , Prasad Deeksha , Kannabiran Chitra , Singh Vivek , Ramappa Muralidhar 
Published: September 2022

Abstract
Background
Congenital hereditary endothelial dystrophy (CHED) is a rare form of corneal dystrophy caused by SLC4A11 gene variations. This study aims to find the genetic alterations in SLC4A11, in two Indian familial CHED cases with affected members n = 3 and n = 2 respectively and five sporadic CHED cases using direct sequencing, followed by in silico analysis and characterization of the identified variants.

Results
All three affected members of the first CHED family were identified with a novel homozygous c.1514C > G (p.Ser489Trp) variation while second family showed presence of a compound heterozygous variation c.529A > C (p.Arg161Arg) + c.2461insT (p.Val805fs). Among five sporadic cases, two showed novel changes, homozygous c.1487G > T (p.Ser480Ile) and c.620-2A > G, while the other one had previously reported homozygous c.2653C > T (p.Arg869Cys) variation. The remaining two cases did not reveal the presence of SLC4A11-related pathogenic variations. The identified variations were excluded from the Indian control (n = 80). In silico analysis using homology-based protein modeling and pathogenicity prediction tools, which revealed these alterations as pathogenic, changing their protein stability, local flexibility, residue contact clashes, and the hydrogen bond interactions.

Conclusions
This study contributed to the CHED mutational spectrum, adding four novel variations and confirming a previously reported one. It demonstrates different type of variations in CHED cases, including coding, non-coding, homozygous, synonymous, and compound heterozygous variations. The identified variations revealed different degrees of pathogenic effects in silico. Moreover, two sporadic cases could not be identified with pathogenic variation emphasizing the involvement of other genes or genetic mechanisms.
TGF-β signaling in the tumor metabolic microenvironment and targeted therapies
Authors: Shi Xueke , Yang Jin , Deng Shuzhi , Xu Hongdan , Wu Deyang , Zeng Qingxiang , Wang Shimeng , Hu Tao , Wu Fanglong , Zhou Hongmei 
Published: September 2022

AbstractTransforming growth factor-β (TGF-β) signaling has a paradoxical role in cancer progression, and it acts as a tumor suppressor in the early stages but a tumor promoter in the late stages of cancer. Once cancer cells are generated, TGF-β signaling is responsible for the orchestration of the immunosuppressive tumor microenvironment (TME) and supports cancer growth, invasion, metastasis, recurrence, and therapy resistance. These progressive behaviors are driven by an “engine” of the metabolic reprogramming in cancer. Recent studies have revealed that TGF-β signaling regulates cancer metabolic reprogramming and is a metabolic driver in the tumor metabolic microenvironment (TMME). Intriguingly, TGF-β ligands act as an “endocrine” cytokine and influence host metabolism. Therefore, having insight into the role of TGF-β signaling in the TMME is instrumental for acknowledging its wide range of effects and designing new cancer treatment strategies. Herein, we try to illustrate the concise definition of TMME based on the published literature. Then, we review the metabolic reprogramming in the TMME and elaborate on the contribution of TGF-β to metabolic rewiring at the cellular (intracellular), tissular (intercellular), and organismal (cancer-host) levels. Furthermore, we propose three potential applications of targeting TGF-β-dependent mechanism reprogramming, paving the way for TGF-β-related antitumor therapy from the perspective of metabolism.