bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with Combined Resveratrol and Myoinositol Ameliorates Endocrine, Metabolic Alterations and Perceived Stress Response in Women with PCOS: A Double-Blind Randomized Clinical Trial
Authors: Hassan Sehresh , Shah Mohsin , Malik Muhammad Omar , Ehtesham Ehtesham , Habib Hamid , Rauf Bushra 
Published: February 2022

Abstract
Purpose: The present study aimed to assess whether treatment with combined resveratrol and myoinositol is more effective in ameliorating the altered parameters associated with PCOS when compared to the combined metformin and pioglitazone therapy.Method: One hundred and ten obese, infertile PCOS women, aged 20-35 years were randomly assigned into two treatment arms. Participants in arm-1 (n=55), received combination of metformin and pioglitazone (1000 mg and 30 mg, respectively), once daily, while those in arm-2 (n=55) received combination of resveratrol and myoinositol (2000 mg and 2000 mg, respectively) once daily for 12 weeks. Evaluations performed at baseline were repeated after 3 months of therapy. The endocrine and metabolic derangements were assessed by measuring serum levels of testosterone, luteinizing hormone, follicle stimulating hormone, adiponectin and insulin using ELISA. Cohen’s perceived stress scale (PSS) was employed as a subjective measure of stress. Results: Pre-treatment PCOS women in both the arms (arm-1 and arm-2) had remarkably elevated serum testosterone and insulin concentrations, low serum adiponectin and high perceived stress response scores. The treatment reduced the altered endocrine indices in arm-2 (resveratrol and myoinositol) participants, manifested by statistically significant reduction in serum testosterone level (p=0.001) and notably increased serum adiponectin level (p=0.001). Interestingly, the hormonal profile, including serum LH and FSH levels also decreased (p<0.001) along with a marked reduction in the ovarian volume (p=0.001) in arm-2 participants. There was a significant reduction in BMI (p<0.001) and an improvement in waist-hip ratio (p<0.001) in arm-2 participants compared to arm-1 group. The PSS scores of the arm-2 subjects improved significantly (p<0.001) whereas, the Ferrimen-gallwey score was improved in both the arms (arm-1 and arm-2; p= 0.010 and 0.008 respectively) however, the change was highly significant in arm-2 (resveratrol and myoinositol). Interestingly, the menstrual regularity was 81.4% in arm-2 while 18.2% in arm-1. We conclude that the therapeutic intervention with combined resveratrol and myoinositol is more effective in ameliorating altered endocrine, metabolic indices and stress burden and could be of clinical importance in high risk group of obese, infertile married PCOS affected women. Trial Registration: Trial registration: ClinicalTials.gov Trial No: NCT04867252. Registered 24 April, 2021, http://clinicaltrials.gov./ct2/show/NCT04867252
Novel RIPK1 Mutations Causing Infantile-onset IBD with Inflammatory and Fistulizing Features
Authors: Sultan Mutaz , Adawi Mohammad , Kol Nitzan , McCourt Blake , Adawi Ihda , Werner Lael , Lev Atar , Snapper Scott , Barel Ortal , Konnikova Liza , Somech Raz , Shouval Dror S. 
Published: February 2022

Abstract
Purpose: Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important regulator of necroptosis and inflammatory responses. We present the clinical features, genetic analysis and immune work-up of two patients with infantile-onset inflammatory bowel disease (IBD) resulting from novel RIPK1 mutations.Methods: Whole exome and Sanger sequencing was performed in two IBD patients. Mass cytometry time of flight (CyTOF) was conducted for in-depth immunophenotyping on one of the patient’s peripheral blood mononuclear cells, and compared to control subjects and patients with Crohn’s disease.Results: The patients presented with severe colitis and perianal fistulas in the first months of life, without severe/atypical infections. Genetic studies identified novel and pathogenic genetic variants in RIPK1. Using CyTOF unbiased clustering analysis, we identified peripheral immune dysregulation in one of these patients, characterized by an increase in IFNγ CD8+ T cells along with a decrease in monocytes, dendritic cells and B cells. Moreover, RIPK1-deficient patient’s immune cells exhibited decreased IL-6 production in response to LPS across multiple cell types including T cells, B cells and innate immune cells. Summary: Mutations in RIPK1 should be considered in very young patients presenting with colitis and perianal fistulas. Given RIPK1’s role in inflammasome activation, but also in epithelial cells, it is unclear whether IL1 blockade or allogeneic hematopoietic stem cell transplantation can suppress or cure the hyper-inflammatory response in these patients. Additional studies in humans are required to better define the role of RIPK1 in regulating intestinal immune responses, and how treatment can be optimized for patients with RIPK1 deficiency.
Responsible Gambling Through a Motivational Telephone Intervention to High-risk Gamblers – an Evaluation of User Satisfaction and Subjective Intervention Effects
Authors: Håkansson Anders , Franklin Katja , Dahlström Maria , Lyckberg Axel 
Published: February 2022

Abstract
Background: Problem gambling causes major social and psychiatric consequences, and there is need to develop feasible harm-reducing or therapeutic interventions. It has been suggested that gambling operators with responsible gambling intentions can intervene in order to identify and help reduce the harm in problem gamblers. However, user satisfaction, and the risk of negative reactions and gamblers’ transfer to other operators, rarely have been explored scientifically.Methods: This is a retrospective survey study of gamblers reached by a motivational, telephone intervention by the Swedish state-owned gambling operator (Svenska Spel), addressing gamblers with indicators of high-risk gambling practices (n=197). Surveys were answered approximately 10 days after the intervention. Results: Thirty-seven percent perceived their gambling to have decreased due to the intervention, whereas seven percent perceived their gambling instead had increased. A large majority (80 percent) reported a subjective favorable experience from the intervention. Forty percent reported gambling on other operators than Svenska Spel after the intervention, but only seven percent gambled on a new operator following the intervention. Conclusions: Survey data in gamblers reached with a motivational telephone intervention present mainly promising findings, and should be replicated in future studies in larger samples. The main findings display an overwhelmingly favorable subjective experience, and a limited risk of gamblers migrating to other operators.
Associations Among Brain Size and Social-Modulating Hormones with Aggression and Cognitive Performance in a Monogamous Cichlid Fish
Authors: Brandão Manuela Lombardi , de Lima Sheila Pereira , Carvalho Thais Billalba , Gonçalves-de-Freitas Eliane 
Published: February 2022

Abstract
Social behavior is shaped by neural and endocrine mechanisms. In this framework, the social brain hypothesis assumes that bigger brains are selected to cope with complex social environments. On the other hand, hormones can act through organizational and activational effects, modulating brain function during ontogeny and in a fast-changing environment. Here, we test correlations among social-modulating hormones – cortisol, testosterone (T), and 11-ketotestosterone (11KT) – and the volume of specific brain areas with individuals’ social aggression and cognitive abilities in both males and females of the pearl cichlid Geophagus brasiliensis. We observed that, although both parents present similar roles during parental care – biparental brood care – reflecting in similar brain volumes, besides social and cognitive behaviors, the correlation between these factors and hormone levels are different comparing sexes. Females are associated with cortisol, which possibly enhances their cognitive performance, and is linked to bigger telencephalons and diencephalons. Males are influenced by testosterone and its conversion into 11KT, which seems to modulate their behavior. Thus, males’ and females’ social behaviors seem to be evolutionarily driven by similar brains, yet different hormonal activation for coping with the social environment.
Is Land-Applying Biosolids to Agricultural Areas “Sustainable”? Part One: Assessing the Potential Chronic, Sublethal and Lethal Ecotoxicity of Biosolids on Folsomia Candida and Lumbricus Terrestris.
Authors: Puddephatt Karen Joan , McCarthy Lynda Helen , Serre Bryant Micheal 
Published: February 2022

Abstract
The ecotoxicity of biosolids has been studied extensively using single-compound toxicity testing and ‘spiking’ studies; however, little knowledge exists on the ecotoxicity of biosolids as they are land-applied in the Canadian context. The purpose of this study is to elucidate the chronic, sublethal (i.e., behavioural), and lethal impacts of land- applying biosolids on the environmentally-relevant Folsomia candida (springtails) and Lumbricus terrestris (earthworms) and concomitantly ascertain whether the use of biosolids for nutrient amendment is a sustainable practice. This study is part of a larger multi-compartment program which includes terrestrial plants and aquatic arthropods. After an extensive review of government protocols and existing research in the literature, the current study attempted to elucidate the true nature of the potential ecotoxicity of land-applying biosolids, within a laboratory context. Protocols were developed or modified (e.g., using Evans’ boxes (Evans 1947) for chronic and sublethal testing on L. terrestris). Subsequently, two biosolids were tested on springtails and earthworms using avoidance and reproductive bioassay endpoints, at application rates that are standard (8 tonnes ha-1) and worst-case scenarios (22 tonnes ha-1). Results indicated no effect of biosolids at the environmentally-relevant concentration; the worst-case scenario exhibited a positive significantly significant relationship (indicating preference for treatment conditions). We suggest that further assessment of the potential ecotoxicological impact of biosolids employ i) environmentally-relevant organisms, ii) appropriate bioassays including the use of whole-organism endpoints, and iii) multi-kingdom testing (e.g., Kingdom Plantae, Animalia) to comprehensively elucidate answers. Lastly, in situ (field assays) are strongly encouraged in future studies.
Computational Study of the Relative Stability of Some Glass-Ionomer Cement-Forming Molecules
Authors: Gaviria Jair , Quijano Silvia , Quijano Jairo , RUIZ PABLO 
Published: February 2022

Abstract
This work is part of a larger study whose main objective was to find a series of promising molecules to be used as glass-ionomer type materials. The project was divided into 3 successive stages; the results of the first stage have been previously published and were used to continue the study. The molecules evaluated in the second stage were constructed by adding a glycidyl methacrylate molecule to the carboxylic groups of the polyacids selected in the previous stage. The modeling was done using the density functional theory for M06-2X/6-311G(d,p). The results indicate that the addition over the carboxylic groups of the fraction of the molecule corresponding to itaconic acid, is thermodynamically favored. The final stage was modeled with the M06 functional, and consisted of obtaining basic structures of glass-ionomer-type materials, by acid-base reaction between the molecules resulting from the second stage with individual ions of Ca (2+), Zn (2+) or Al (+ 3). It was concluded that aluminum atoms generate more compact structures that would correlate with more resistant materials.
Therapeutic Effects of Triptolide on the Balance of Th17/Treg Cells via AKT/mTOR/p70S6k Signaling Pathway in Lupus-like Mice
Authors: Sun Qice , Liu Yan , Lu Dingqi , Ji Lina , Wang Weijie , Wang Xinchang , Fan Yongsheng , Xie Guanqun 
Published: February 2022

Abstract
T cell subsets play a critical role in immune regulation. T helper 17 (Th17) cells induce tissue inflammation and autoimmune response while regulatory T (Treg) cells mediate autoimmune tolerance and inhibit autoimmune response. Recent studies have shown that the important factors for the pathogenesis and disease activity of systemic lupus erythematosus (SLE), a chronic inflammatory autoimmune disease, are an increased number of Th17 cells and a decreased number or reduced functions of Treg cells. Triptolide is the main active ingredient of Tripterygium wilfordii Hook F (TWHF). It not only has anti-inflammatory, antiproliferative, immune modulation, and proapoptotic activity effects, but is also effective in treating SLE. However, the underlying mechanism of how triptolide works is still unclear. For the purpose of evaluating the impact of triptolide on the induction of Th17 and Treg cells, we conducted relevant experiments with respect to the number and activities of Th17 and Treg cells in vivo and in vitro. In vivo, intragastrically administered triptolide effectively ameliorated the clinical and histological symptoms in lupus-like mice, increased the number of induced Treg cells and reduced the number of Th17 cells in the spleen and their secretion. In vitro, triptolide is able to promote the differentiation of Treg cells and inhibit Th17 formation by inhibiting the AKT/mTOR/p70S6K pathway. Therefore, we posit that triptolide can help to deter the development of inflammation and ultimately treat SLE through regulation of the Th17 and Treg cells balance.
Influence of differences in bone morphology on stress distribution patterns across the trapeziometacarpal joint
Authors: Matsui Yuichiro , Tsukuda Yukinori , Endo Kaori , Matsui Yuki , Kawamura Daisuke , Iwasaki Norimasa 
Published: February 2022

Abstract
We aimed to clarify the effects of morphological patterns of the trapezium and first metacarpal on stress distribution across the articular surface of the trapeziometacarpal (TMC) joint using computed tomography osteoabsorptiometry. Thirty-three patients with normal TMC joints were evaluated. The percentages of the high-density areas in the radial-dorsal and ulnar-volar regions of the trapezium were significantly higher than that in the ulnar-dorsal region, and that of the ulnar-dorsal region of the first metacarpal was significantly lower than in the other three regions. The percentage of the high-density area of the radial-dorsal region of the trapezium and trapezial inclination (TI) showed a significant positive correlation, and the percentages of the high-density areas in the ulnar-dorsal and ulnar-volar regions had significant negative correlations with TI at the articular surface of the first metacarpal. These results indicate that bony morphologic differences in the trapezium affect the stress distribution pattern through the TMC joint.
PT-symmetric distinction of three states and its implementation on a cloud quantum processor
Authors: Balytskyi Yaroslav , Kotukh Yevgen , Khalimov Gennadiy , Chang Sang-Yoon 
Published: February 2022

Abstract
We present a novel $\mathcal{PT}$-symmetric approach for discriminating three pure qubit states and its implementation by the dilation method. Our approach based on the dilation method manipulating the Hilbert space of the system by two-staged $\mathcal{PT}$-symmetric evolution expedites the three-state discrimination process at the cost of introducing an inconclusive outcome. This modification of the Hilbert space of the qubit makes it possible to eliminate one of three states in the limit $\alpha\rightarrow\pm\frac{\pi}{2}$ in the vicinity of the exceptional point corresponding to coalescing eigenvectors and eigenvalues, effectively reducing the problem to two-state discrimination, or reducing the geometry to the mirror-symmetric states for which an efficient discrimination strategy is developed. To demonstrate the effectiveness of our approach, we implement it on a superconducting quantum processor provided by IBM Quantum Experience employing an ancilla qubit. We conclude our paper by identifying potential applications, including those in quantum communication and cryptography, to facilitate further research and development.
Initial experience of a deep learning application for the differentiation of Kikuchi-Fujimoto’s disease from tuberculous lymphadenitis on neck CECT
Authors: Kim Byung Hun , Lee Changhwan , Lee Ji Young , Tae Kyung 
Published: February 2022

Abstract
Neck contrast-enhanced CT (CECT) is a routine tool used to evaluate patients with cervical lymphadenopathy. This study aimed to evaluate the ability of convolutional neural networks (CNNs) to classify Kikuchi-Fujimoto’s disease (KD) and cervical tuberculous lymphadenitis (CTL) on neck CECT in patients with benign cervical lymphadenopathy. A retrospective analysis of consecutive patients with biopsy-confirmed KD and CTL in a single center, from January 2012 to June 2020 was performed. This study included 198 patients of whom 125 patients (mean age, 25.1 years ± 8.7, 31 men) had KD and 73 patients (mean age, 41.0 years ± 16.8, 34 men) had CTL. A neuroradiologist manually labelled the enlarged lymph nodes on the CECT images. Using these labels as the reference standard, a CNN was developed to classify the findings as KD or CTL. The CT images were divided into training (70%), validation (10%), and test (20%) subsets. The Cut&Remain method was applied to improve performance. For the test set, the best area under the receiver operating characteristic curve for classifying KD from CTL was 0.91. Our findings show that the differentiation of KD from CTL on neck CECT using a CNN is feasible with high diagnostic performance.
A Hybrid Method Based on Semi-Supervised Learning for Relation Extraction in Chinese EMRs
Authors: Yang Chunming , Xiao Dan , Luo Yuanyuan , Li Bo , Zhao Xujian , Zhang Hui 
Published: February 2022

Abstract
Background: Building a large-scale medical knowledge graphs needs to automatically extract the relations between entities from electronic medical records(EMRs) . The main challenges are the scarcity of available labeled corpus and the identification of complexity semantic relations in text of Chinese EMRs. A hybrid method based on semi-supervised learning is proposed to extract the medical entity relations from small-scale complex Chinese EMRs. Methods: The semantic features of sentences are extracted by a residual network(ResNet) and the long dependent information is captured by bidirectional GRU(Gated Recurrent Unit). Then the attention mechanism is used to assign weights for the extracted features respectively, and the output of two attention mechanisms is integrated for relation prediction. We adjusted the training process with manually annotated small-scale relational corpus and bootstrapping semi-supervised learning algorithm, and continuously expanded the datasets during the training process. Results: We constructed a small corpus of Chinese EMRs relation extraction based on the EMR datasets released at the CCKS(China Conference on Knowledge Graph and Semantic Computing). The experimental results show that the best F1-score of the proposed method on the overall relation categories reaches 89.78%, which is 13.07% higher than the baseline CNN.
CLUSTER: A biomarker-integrated targeted therapy study in patients with advanced non-small cell lung cancer
Authors: Zhou Qing , Chen Hua-Jun , Wang Bin-Chao , Wang Zhen , Tu Hai-Yan , Xu Chongrui , Zheng Ming-Ying , Bai Xiao-Yan , Sun Yue-Li , Yan Hong-hong , Gan Bin , Tao Hong , Wang Yingying , Zhao Sylvia , Yang Jin-Ji , Lai Clinton , Wu Yi-Long 
Published: February 2022

Abstract
The CLUSTER umbrella trial simultaneously investigated the efficacy of multiple targeted therapies in Chinese patients with advanced non-small cell lung cancer and pre-specified genetic alterations. Patients were assigned to receive capmatinib (METi), ceritinib (ALKi), binimetinib (MEKi), or alpelisib (PI3Kαi) matched to their genetic alteration. The overall response rate (ORR) and safety of each treatment were determined. Ceritinib met the pre‑specified statistical threshold for efficacy with an ORR of 73%, whereas an ORR of 19% and 9% were attained with capmatinib and binimetinib, respectively. Although not a predefined endpoint, a post-hoc analysis of the overall anti-tumor activity in all treated patients showed encouraging results. Despite the limited number of patients in some of the treatment arms and the stringent criteria for preliminary activity, these findings confirm the feasibility of conducting biomarker-integrated studies in China, and warrant the implementation of further umbrella trials to simultaneously evaluate the efficacy of multiple targeted treatments. Trial registration number: NCT02276027
A Novel Tumor Suppressor Gene, TMEM171, Inhibits the Development of Gastric Cancer by Dephosphorylating IKBα and Inactivating the NF-kB Signaling Pathway
Authors: Li De-feng , Tang Qi , Yang Mei-feng , Bing Yu-ling , Peng Quan-zhou , Wang Li-sheng , Yao Jun 
Published: February 2022

Abstract
Background: Gastric cancer (GC) is one of the most common malignant tumors with an unsatisfactory prognosis worldwide. Therefore, it is urgently necessary to explore the mechanism underlying the tumorigenesis of GC. Methods: In the present study, we identified that TMEM171 was down-regulated in GC tissues, and its expression was closely associated with the prognosis of GC patients based on the data from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). Subsequently, qRT-PCR, Western blotting analysis, and immunohistochemistry (IHC) assay were performed to detect the expression of TMEM171 in GC tissues and cell lines. The functional roles and underlying mechanisms of TMEM171 involved in GC growth were also explored in vitro and in vivo.Results: TMEM171 was remarkably down-regulated in GC tissues and GC cell lines. Functionally, overexpression of TMEM171 suppressed the proliferation of GC cells and promoted the apoptosis of GC cells, whereas depletion of TMEM171 contributed to the opposite trend in vitro and in vivo. TMEM171 functioned as an inhibitor for GC proliferation through dephosphorylating IκBα and then inactivating the canonical NF-κB signaling pathway. Conclusions: This study revealed the vital role of TMEM171 in GC, highlighting the regulatory function of the TMEM171/IκBα/NF-κB signaling pathway in modulating GC progression. Collectively, our findings provided a novel prognostic and therapeutic target for GC patients.
Two distinct kinases responsible for the phosphorylation of tyrosine residues of Gab2 in neutrophil precursor cell upon G-CSF stimulation.
Authors: Miyoshi Mana , Kawano Shun-ichiro , Zhao Xianglin , Ide Toru , Murakami Hiroshi 
Published: February 2022

Abstract
Gab2 is one of the most heavily tyrosine-phosphorylated protein in granulocyte precursor cell, GM-I62-1, upon G-CSF stimulation. Effects of several pharmacological inhibitors to tyrosine kinases were examined on the tyrosine phosphorylation of Gab2 upon G-CSF stimulation. Specific Src kinase inhibitor, PP1, had marginal effects, if any, on the Gab2 tyrosine phosphorylation. In contrast, Syk specific inhibitors, Piceatannol and GS-9973, had partial but distinct inhibitory effects on the Gab2 tyrosine phosphorylation upon G-CSF stimulation. When the tyrosine residues are phosphorylated, downstream effector molecules, SHP2 and p85 subunit of PI3K, are known to bind to these phosphorylated residues of Gab2 through their SH2 domains. Pretreatments of cells with Syk specific inhibitors reduced the SHP2 binding to Gab2. However, no inhibitory effect of these inhibitors on p85 binding to Gab2 was observed. These observations indicated that Syk phosphorylates tyrosine residues of SHP2 binding sites of Gab2, and that the tyrosine residues of Gab2 to which p85 subunit of PI3K binds upon G-CSF stimulation are phosphorylated by other tyrosine kinase(s).