bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying Artificial Intelligence to create risk stratification visualization for underserved patients to improve population health in a community health setting
Authors: Roosan Don , Roosan Moom R , Kim Soyoung , Law Anandi V , Sanine Christ
Published: May 2022

Current healthcare visualizations utilize unstructured Electronic Health Record (EHR) data that lack user requirement analysis for intuitive visualizations. Since clinicians are the end-users, it is crucial to consider end users’ input to improve clinical workflow efficiency. In this paper, we developed a user-centered design through cognitive task analysis (CTA) to visualize unstructured EHR data using artificial intelligence (AI) and natural language processing (NLP). The research team conducted CTA with 8 clinicians. The interviews were transcribed, and a content analysis was performed. Themes were coded, and user requirements helped us to understand the clinical workflow. The CTA resulted in 5 different themes: 1) Gathering patient information, 2) Filtering and searching for necessary information, 3) Subjective, objective assessment, plan of the patient, 4) Visualization of unstructured EHR data, and 5) Progression of trends and comparisons in patients. The intuitive visualization dashboard utilizing unstructured EHR population data was successfully developed. Design elements included an interactive dashboard with a snapshot and basic information for all patients, filter and search keywords, and visualizations of patient trends and lab results through graphs. Finally, a system usability scale (SUS) survey was completed to assess the usability of the dashboard by 20 participants. The completed 20 SUS surveys resulted in an average score of 80.9, which concluded that the platform had a high usability. The health analytics dashboard demonstrated unstructured data containing diverse information that can support identifying underserved populations, enhance workflow efficiency and create intuitive design interface.
In-Silico Target Prediction by Ensemble Chemogenomic Model based on Multi-Scale Information of Chemical Structures and Protein Sequences
Authors: Yang Su-Qing , Zhang Liu-Xia , Ge You-Jin , Hu Jian-Xin , Shen Cheng-Ying , Lu Ai-Ping , Hou Ting-Jun , Cao Dong-Sheng
Published: May 2022

Identification and validation of bioactive small-molecule targets is a significant challenge in drug discovery. In recent years, various in-silico approaches have been proposed to expedite time- and resource-consuming experiments for target detection. Herein, we developed several chemogenomic models for target prediction based on multi-scale information of chemical structures and protein sequences. By combining the information of a compound with multiple protein targets together and putting these compound-target pairs into a well-established model, the scores to indicate whether there are interactions between compounds and targets can be derived, and thus a target prediction task can be completed by sorting the outputted scores. To improve the prediction performance, we constructed several chemogenomic models using multi-scale information of chemical structures and protein sequences, and the ensemble model with the best performance was used as our final model. The model was validated by various strategies and external datasets and the promising target prediction capability of the model, i.e., the fraction of known targets identified in the top-k (1 to 10) list of the potential target candidates suggested by the model, was confirmed. Compared with multiple state-of-art target prediction methods, our model showed equivalent or better predictive ability in terms of the top-k predictions. It is expected that our method can be utilized as a powerful computational tool to narrow down the potential targets for experimental testing.
CHEERS is reliable for online use: a randomized crossover paper versus online test-retest reliability study.
Authors: Lafave Lynne M.Z.
Published: May 2022

BackgroundThe creating healthy eating and active environments survey (CHEERS) is an audit tool used to assess the nutrition and physical activity environment in early childhood education and care (ECEC) centres. Availability of the tool has been limited to paper-based versions. Digital health initiatives offer improved reach and immediacy of support for community-based clients through novel technology products. In order to provide increased access to the CHEERS tool, an online version was developed. The objective of this study was to assess the reliability of an online version of CHEERS.MethodsUtilizing a randomized crossover design, ECEC educators completed either a paper-based or online-based survey and then the opposite mode with a two to three-week interval. The intraclass correlation coefficient (ICC, with 95% confidence interval) was used to determine the reliability between test and retest. Absolute index of reliability in the original measurement was assessed through the standard error of measurement (SEM = SD × √1-ICC). The smallest amount of change not due to inherent variation was assessed by determining minimal detectable change at the 95% confidence level (MDC95 = SEM × 1.96 ×√2; MDC95% = MDC95/mean ×100).ResultsTest-retest reliability was good to excellent for the online-based CHEERS total score (ICC = 0.86) and for each of the four subscales: food served (ICC = 0.82), healthy eating environment (ICC = 0.76), program planning (ICC = 0.76), and physical activity environment (ICC = 0.79). The SEM, MDC95, and MDC95% for the CHEERS overall score were 0.79, 2.19, and 9.6%, respectively.ConclusionsThe results of this study demonstrate that the online-based and paper-based versions of the CHEERS audit tool share comparable accuracy. The CHEERS tool can be reliably implemented in an online environment and this provides users an alternative means to complete the centre-based health assessment. The advantage of the online-based version includes user accessibility and the potential to develop a feedback response for participants using digitally collected data.
single-port thoracoscopic removal of an azygos vein aneurysm: a case report and literature review
Authors: YI YAO , Hu Qiuxia , Xie Xiaoyang , Liu caiyang , Lei Yu , Li Xiaoliang , Wang Yi , Liu Gaohua , Yang yanhui , Luo Lei , Li Ji
Published: May 2022

Background:Azygos vein aneurysms (AVAs) are extremely rare. The majority of patients have no obvious clinical symptoms and are found by physical examination or by chance. There are limited clinical treatment experience that can be referred and there are no clear guidelines or research evidence to guide the standard of surgical and interventional therapy. Here, we report a patient with idiopathic AVA whose three-dimensional reconstruction of the tumor was completed before surgery. On the basis of three-dimensional reconstruction, the single-port thoracoscopic resection of AVA was successfully completed and reported for the first time. The previous reported cases were summarized to provide experience for the diagnosis and treatment of patients with AVAs.Case presentation:A 56-year-old man was transferred to our hospital due to "dysphagia". The diagnosis of AVA was performed after further completed enhanced computed tomography, gastroscopy, fiberoptic bronchoscopy, and three-dimensional reconstruction. Due to the patient had symptoms of dysphagia and the AVA had the risk of rupture, the patient received single-port thoracoscopic surgery. After the operation, his dysphagia disappeared. The postoperative pathology confirmed hemangioma. The patient was discharged on the three day after surgery without any complications. Conclusions:AVAs are rare. Preoperative three-dimensiona reconstruction is of great significance for surgeon to clear disease diagnosis, formulate the surgical plans, avoid damage the surrounding vital organs, and reduce intraoperative bleeding. Despite thoracoscopic surgery to remove AVA is difficult and has a high risk of bleeding, more minimally invasive single-port thoracoscopic surgery is also safe and effective for the treatment of AVAs.
Retrospective Study of hypofractionated stereotactic radiotherapy Combined with whole brain radiotherapy for Patients with Brain Metastases
Authors: Xie Xie , Peng Hong-Hua , Zhang Xi , Pan Yu-Liang , Zhang Zhen , Cao Pei-guo
Published: May 2022

Background and purpose: To evaluate the clinical outcomes of hypofractionated stereotactic radiotherapy (HFSRT) combined with whole brain radiotherapy (WBRT) in patients with brain metastases (BMs).Materials and methods: From May 2018 to July 2020, 50 patients (111 lesions) received HFSRT (18Gy/3F) +WBRT (40Gy/20F). The RECIST 1.1 and RANO-BM criteria were used to evaluate treatment efficacy. Five prognostic indexes (RPA, GPA, SIR, BS-BM, and GGS) were applied. The primary endpoint was intracranial local control (iLC). Secondary endpoints were overall survival (OS) and the safety of treatment.Results: Intracranial objective response rates (iORR) using the RECIST 1.1 and RANO-BM criteria were 62.1% and 58.6%, respectively. The iLC rate was 93.1%, the 6- and 12-month iLC rates were 90.8% and 57.4%, respectively. The median intracranial progression-free survival (iPFS) was not reached (range 0−23 months). The 6-, 12-, and 24-month OS rates were 74.2%, 58.2%, and 22.9%, respectively. The KPS score showed statistical significance in univariate analysis of survival. The 6, 12, and 24 month OS rates for patients with KPS ≥70 were 83.8%, 70.5%, and 29.7%, respectively. The median survival time (MST) for all patients and for patients with KPS ≥70 were 13.6 and 16.5 months, respectively. Sex, KPS score, and gross tumor volume were significant factors in the multivariate analysis of survival. OS was significantly associated with RPA, SIR, BS-BM, and GGS classes. No acute toxicities of grade 3 or higher were noted.Conclusion: HFSRT combined with WBRT is a safe and effective local treatment modality for BM patients.
Dual-regulated mechanism of EZH2 and KDM6A on SALL4 modulates tumor progression via Wnt/β-catenin pathway in gastric cancer
Authors: Ren Lei , deng Hong , Jiang Yu , Liu Chunfeng
Published: May 2022

Background: The molecular mechanism underlying the progression of gastric cancer (GC) remains unclear, the overexpression level of SALL4 has been demonstrated in many cancers and participated in tumorigenesis, however, it is still ambiguous for the expression and function of SALL4 in GC, especially its upstream mechanistic modulators.Method: Analysis of discrepant gene expression in GC and normal gastric tissues from The Cancer Genome Atlas (TCGA) dataset. Cultured GC cell lines were treated with siEZH2 and siKDM6A and checked for their influences on SALL4, the transduction molecules of KDM6A/EZH2-SALL4-β-catenin signaling were quantified in the GC cells.Results: Here, we showed that only SALL4 levels of SALL family members were upregulated in nonpaired and paired GC tissues than those in corresponding normal tissues and were associated with its histological types, pathological stages, TNM stages, and overall survival from the TCGA dataset. SALL4 level was elevated in GC cells compared to normal gastric epithelial cell line (GES-1) and was correlated to cancer cell progression and invasion through the Wnt/β-catenin pathway in GC, which levels would be separately upregulated or downregulated by KDM6A or EZH2.Conclusion: We first proposed and demonstrated that SALL4 promoted GC cell progression via the Wnt/β-catenin pathway, which was mediated by the dual regulation of EZH2 and KDM6A on SALL4. This mechanistic pathway in gastric cancer represents a novel targetable pathway.
Blood-CSF-barrier permeability in tuberculous meningitis and its association with clinical, MRI and inflammatory cytokines
Authors: Shukla Ruchi , Kalita Jayantee , Haldar Rudrashish , Misra Usha K
Published: May 2022

Objective: Blood -cerebrospinal fluid (B-CSF) barrier disruption in tuberculous meningitis (TBM) may be mediated by inflammatory cytokines and may determine clinico–radiological severity and outcome. We report B-CSF permeability in TBM and its relationship with inflammatory cytokines (TNF-α, IL-1β and IL-6), clinical severity, MRI changes and outcome.Methods: Fifty-five TBM patients with a median age of 26 years were included. Their clinical, CSF and MRI findings were noted. Severity of meningitis was graded into stages I to III. Cranial MRI was done and presence of exudates, granuloma, hydrocephalus and infarctions was notes. B-CSF permeability was assessed by a ratio of CSF albumin to serum albumin (Qalb).Concentration of TNF- α, IL-1β and IL-6 in CSF was measured by CBA. Results: The Qalb in the patients was more than mean+2.5 SD of controls. In TBM, Qalb correlated with TNF- α (r=0.36; p=0.01), CSF cells (r=0.29; p=0.02) and exudate on MRI (0.18 ± 0.009 Vs 0.13 ± 0.008; p=0.04). There was however no association of Qalb with demographic variables, stage, tuberculoma, infraction and hydrocephalus. At 6 months, 11(20%) died, 10(18.2%) had poor and 34(61.8%) had good recovery. Conclusion: B-CSF permeability in TBM correlated with TNF-α, CSF pleocytosis and exudates but not with severity of meningitis and outcome.
DNA methylation as a potential mediator of the association between indoor air pollution and neurodevelopmental delay in a South African birth cohort
Authors: Feil Dakotah , Abrishamcar Sarina , Christensen Grace M. , Vanker Aneesa , Koen Nastassja , Kilanowski Anna , Hoffman Nadia , Wedderburn Catherine J. , Donald Kirsten A. , Kobor Michael S , Zar Heather J , Stein Dan J , Hüls Anke
Published: May 2022

Background
Exposure to indoor air pollution during pregnancy has been linked to neurodevelopmental delay in toddlers. Epigenetic modification, particularly DNA methylation (DNAm), may explain this link. In this study, we employed three high-dimensional mediation analysis methods (HIMA, DACT, and gHMA) followed by causal mediation analysis to identify differentially methylated CpG sites and genes that mediate the association between indoor air pollution and neurodevelopmental delay. Analyses were performed using data from 142 mother-child pairs from a South African birth cohort, the Drakenstein Child Health Study. DNAm from cord blood was measured using the Infinium MethylationEPIC and HumanMethylation450 arrays. Neurodevelopment was assessed at age 2 years using the Bayley Scores of Infant and Toddler Development, 3rd edition across four domains (cognitive development, general adaptive behavior, language, and motor function). Particulate matter with an aerodynamic diameter of 10µm or less (PM10) was collected inside participants’ homes during the second trimester of pregnancy.
Results
A total of 29 CpG sites and 4 genes (GOPC, RP11-74K11.1, DYRK1A, RNMT) were identified as significant mediators of the association between PM10 and cognitive neurodevelopment. The estimated proportion mediated (95%-confidence interval) ranged from 0.29 [0.01,0.86] for cg00694520 to 0.54 [0.11,1.56] for cg05023582.
Conclusions
Our findings suggest that DNAm may mediate the association between prenatal PM10 exposure and cognitive neurodevelopment. DYRK1A and several genes that our CpG sites mapped to, including CNKSR1, IPO13, IFNGR1, LONP2, and CDH1, are associated with biological pathways implicated in cognitive neurodevelopment and three of our identified CpG sites (cg23560546 [DAPL1], cg22572779 [C6orf218], cg15000966 [NT5C]) have been previously associated with fetal brain development. These findings are novel and add to the limited literature investigating the relationship between indoor air pollution, DNAm, and neurodevelopment, particularly in low- and middle-income country settings and non-white populations.
Topological indices of general relativity and Yang-Mills theory in four-dimensional space-time
Authors: Kurihara Yoshimasa
Published: May 2022

This report investigates general relativity and the Yang-Mills theory in four-dimensional space-time using the common mathematical framework, the Chern-Weil theory for principal bundles. The whole theory is described owing to the fibre bundle with the GL(4) symmetry, a model of the space-time, and twisting several principal bundles with the gauge symmetry that are a model of force and matter fields.We introduce the Hodge-dual connection in addition to the principal connection into the Lagrangian to make gauge fields have dynamics independent from the Bianchi identity. The duplex superstructure appears in the bundle when a Z2-grading operator exists in a total space of the bundle in general. The Dirac operator appears in the secondary superspace using the one-dimensional Clifford algebra. Thus, it provides topological indices owing to the Atiyah-Singer index theorem. We introduce a novel method, namely the theta-metric space, to discuss topological indices in the hyperbolic space-time manifold. The theta-metric treats the Euclidean and Minkowski spaces simultaneously and defines the topological index in the Minkowski space-time.In this framework, we show several examples of topological indices appearing in the field theory and clarify the physical significance of these indices in the Minkowski space-time.
Usefulness of PIVKA-II for Monitoring After Liver Transplantation in Patients With Hepatocellular Carcinoma
Authors: LÓPEZ FRANCISCO VILLALBA , SÁENZ LUIS FRANCISCO , LORENCIO MARIA ISABEL SÁNCHEZ , GARCÍA VIRGINIA DE LA ORDEN , VELASCO JOSÉ ANTONIO NOGUERA , BERNARDO CARMEN GARCÍA , MAZO ALBERTO BAROJA , ROMERO PABLO RAMÍREZ
Published: May 2022

Background
the high morbidity and mortality of hepatocellular carcinoma (HCC) has encouraged the search for new biomarkers to be used alongside alpha-foetoprotein (AFP) and imaging tests. The aim of this study was to evaluate the clinical contribution of protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC monitoring after liver transplantation (LT) and compare it with AFP, a routinely used tumour marker.
Methods
a total of 46 HCC patients (Milan criteria) were enrolled in this study. Serum levels of PIVKA-II and AFP were measured before transplantation and at 1, 6 months, 1 year and 2 years after transplantation. Clinical features were determined for all the patients that were included.
Results
significant correlations were found between PIVKA-II expression levels and some clinicopathological features, such as tumour size and number of pre-transplant transarterial chemoembolizations (TACEs). Serum levels of PIVKA-II and AFP decreased significantly after LT and increased in patients with tumour recurrence. Combined determination of pre-transplant PIVKA-II and AFP levels improved the predictive ability of each biomarker separately for post-transplant recurrence.
Conclusions
serum PIVKA-II levels were associated with tumour size and with the number of pre-transplant TACEs suggesting that this biomarker may play an important role in predicting disease severity. Furthermore, monitoring PIVKA-II levels in HCC transplant recipients reflects the tumor early recurrence after transplantation and could be used, complementing AFP and imaging tests, as a novel biomarker of this pathology.
Patient-centric synthetic data generation, no reason to risk re-identification in the analysis of biomedical pseudonymised data
Authors: Guillaudeux Morgan , Rousseau Olivia , Petot Julien , Bennis Zineb , Dein Charles-Axel , Goronflot Thomas , Karakachoff Matilde , Limou Sophie , Vince Nicolas , Wargny Matthieu , Gourraud Pierre-Antoine
Published: May 2022

Anonymization is crucial in the era of big data analysis. While nearly all computational methods operate on pseudonymised personal data, re-identification remains a risk. With personal health data, this re-identification risk may be considered a double-crossing of patients’ trust. Herein, we present a new method to generate synthetic data of individual granularity while holding on to patients’ privacy. Developed for sensitive biomedical data, the method is patient-centric as it uses a local model to generate random new synthetic data, called an “avatar”, for each initial sensitive individual. This method is applied to real health data in a clinical trial related to HIV-infected patients (AIDS clinical trial; N=2139, 26 variables, example 1) and the Wisconsin Breast Cancer Diagnosis (WBCD; N=683, 1 10 variables, example 2) observational study to evaluate the protection it provides while retaining the original statistical information. In the light of distance-based privacy metrics, each individual produces an avatar that is on average indistinguishable from 12 other generated avatars for the AIDS clinical trial and 24 for the WBCD observational study. Data transformation via the Avatar method preserved the evaluation of the treatment’s effectiveness for example 1 (original hazard ratio 𝐻𝑅 = 0. 49 (95% CI, 0.39 - 0.63) vs avatar 𝐻𝑅 = 0. 47 (95% CI, 0.37 - 0.60)) and the classification properties for example 2 (original 𝐴𝑈𝐶 = 99. 46 (𝑠𝑡𝑑 = 0. 25) vs avatar 𝐴𝑈𝐶 = 99. 84 (𝑠𝑡𝑑 = 0. 12)). Thanks to the Avatar method, modern-era data analysis should no longer pose a re-identification risk. Avatars enable the creation of value from pseudonymised data analyses by tackling the risk of a privacy breach.
Dilaton in scalar QFT: a no-go theorem in 4-epsilon and 3-epsilon dimensions
Authors: Nogradi Daniel , Ozsvath Balint
Published: May 2022

Spontaneous scale invariance breaking and the associated Goldstone
boson, the dilaton, is investigated in renormalizable, unitary,
interacting non-supersymmetric scalar field theories in
4-\varepsilon4−ε
dimensions. At leading order it is possible to construct models which
give rise to spontaneous scale invariance breaking classically and
indeed a massless dilaton can be identified. Beyond leading order, in
order to have no anomalous scale symmetry breaking in QFT, the models
need to be defined at a Wilson-Fisher fixed point with exact conformal
symmetry. It is shown that this requirement on the couplings is
incompatible with having the type of flat direction which would be
necessary for an exactly massless dilaton. As a result spontaneous scale
symmetry breaking and an exactly massless dilaton can not occur in
renormalizable, unitary 4-\varepsilon4−ε
dimensional scalar QFT. The arguments apply to
\phi^6ϕ6
theory in 3-\varepsilon3−ε
dimensions as well.
Determinants of sanitation and hygiene status among food and drink establishments in Fiche town, Oromia, Ethiopia
Authors: Chane Samuel , Sebsibe Israel , Adibaru Birhanu
Published: May 2022

Poor sanitary conditions of food and drink establishments are the major causes for the occurrence of foodborne illness. The aim of this study was to assess the sanitation and hygiene status and its determinants among food and drink establishments in Fiche town. Binary logistic regression was used to identify the predictor variables. A total of 422 catering establishments were assessed. In the present study, 49.8 and 71.8% of the establishments were involved in undesirable practices of disposing liquid and solid waste in open fields, respectively. The present study showed that 11.6 and 15.6% of catering establishments used three-compartment washing facilities for dish and glass, respectively. Presence of trained staff about food hygiene (adjusted odds ratio (AOR) = 4.84, 95% confidence interval (CI) 2.91–8.03), being licensed (AOR = 3.07, 95% CI 1.41–6.67), regulatory inspection (AOR = 2.74, 95% CI 1.60–4.68), and service year of establishments (AOR = 3.02, 95% CI 1.43–6.35) were the determinant factors. The sanitary conditions of catering establishments in the study area were poor. Therefore, concerned regulatory bodies should routinely inspect the food and drink establishments to strengthen the standards of establishments to satisfactory sanitary situations.
The effectiveness of a water resource tax policy in improving water-use efficiency: a quasi-natural experiment-based approach
Authors: Mu Lan , Zhang Xiaoyan , Cheng Sen , Song Peisong
Published: May 2022

Comprehensively improving the efficiency of water resource utilization is not only an urgent need to resolve the prominent contradiction between water supply and water demand but also an inevitable requirement to promote the harmonious coexistence between humans and nature. The compulsory water resource tax is considered to be a powerful tool for resolving the worldwide water crisis and improving water resource utilization efficiency (WRUE). Based on a quasi-natural experiment of water resource tax policy in China, this study used panel data for 30 provinces (municipalities) from 2011 to 2019 to evaluate the impact of water resource tax policies on WRUE through a multistage difference-in-difference model. The results showed that the water resource policy can effectively improve the utilization efficiency of water resources by optimizing the allocation of resources. In addition, the analysis of the spatial heterogeneity showed that the policy of the water resource tax has a stronger lifting effect on improving water resource-use efficiency in eastern China than that in the central and western regions. This research provided insights into China's water policies that can be used to better manage natural resources.
Retrospective study of triatomines in an endemic region for Chagas disease in the state of Bahia, Brazil
Authors: Santos Jéssica Samile Sousa , Pauda Alini Dias de , Novais Joane Maíra Cavalcante Braga , Magalhães Junior Jairo Torres , Carneiro Ianei de Oliveira , Santos Flavia dos
Published: May 2022

Chagas disease is caused by Trypanosoma cruzi, which has several forms of transmission. Among them, the vector route requires the constant action of the Health Surveillance in the control of triatomines. Our objective is to describe the diversity of triatomines and the rate of natural infection by T. cruzi in these insects, as well as to analyse entomological indicators, through secondary data generated by the Health Surveillance of the municipality of Barra, in the period from 2009 to 2019. The secondary data were subjected to descriptive analysis and the entomological indicators calculated. Williams’ G test and Fisher’s exact test were used to analyse the categorical data. A total of 10,913 triatomines of the genera Rhodnius sp., Panstrongylus sp., Eratyrus sp. and Triatoma sp. were captured, represented by 12 species. Triatoma sordida was the most prevalent 98.66% (10,767/10,913), reflected in the overall infestation index 7.61% (2,555/33,544) and triatomine density 0.24 (8,247/33,544). While the overall infection rate was 0.81% (41/5,048) and remained low during all years. There was significant association for T. sordida in relation to “T. cruzi infection index” and “Developmental stage” and “Capture site”. It is concluded that the municipality of Barra has a high occurrence of triatomines of various species, with T. sordida being the most prevalent species and responsible for the rates of infestation and infection by T. cruzi. The presence of these insects in households is a risk for the domestic cycle of the parasite, and thus can transmit T. cruzi to various domestic animals, including humans.
Insights into New Therapeutic Approaches for the Treatment and Management of
Polycystic Ovary Syndrome: An Updated Review
Authors: Bashir Rohina , Wani Imtiyaz Ahmad , Ganie Mohd. Ashraf
Published: May 2022

Background:

Polycystic ovary syndrome (PCOS) is a long-term, highly prevalent, complex heterogeneous, polygenic endocrine disorder characterized by both metabolic and reproductive disorders. It affects 6-23% of reproductive age women globally

Objective:

This review aims to facilitate an understanding of novel PCOS management approaches and highlights the results from relevant interventional studies from animal and human studies.

Methods:

Manual search on PubMed, Cochrane, Scopus databases was performed for relevant articles, preclinical and clinical trials based on related keywords.

Results:

According to a multitude of studies, PCOS has evolved over time, but a substantial lag remains in management approaches. New insights into the cross-talk between muscle, brain, fat, and ovaries pointed out new therapeutic targets. This review has highlighted the efficacy of a wide spectrum of novel therapeutic agents [Phosphodiesterase-4 Inhibitors, Glucagon-like peptide-1 receptor agonists, nutritional supplements (Vitamins D and K, omega-3, prebiotics, probiotics and synbiotics), fecal microbiota transplantation (FMT) and intestinal cytokine IL-22] as PCOS therapeutic options. These novel therapies combine anti-inflammatory, insulin sensitizing, anti-obesity, and restoration of the gut microbiota and thus hold the potential to address the basic pathogenic mechanisms of PCOS.

Conclusion:

Exhaustive, multicentric and multiethnic studies are vital to generate a network of normative data to better figure out the PCOS trajectory and change prognostic outcomes. Preclinical and clinical data is warranted to corroborate the new therapeutics and direct health care resources accordingly.
Entanglement of Methylation Changes and cGAS-STING Signaling in
Non-Small-Cell Lung Cancer
Authors: Hao Fang
Published: May 2022

Background:

cGAS-STING signaling has been primarily discovered as an important
DNA sensing machinery, bridging innate immunity and adaptive immunity. Beyond its antiviral
response, recent evidence expanded its complicated role in cancer therapy.

Methods:

UALCAN, The TCGA Wander, GEPIA, SMART, TIMER, Kaplan-Meier plotter,
TCGA Data, and cBioPortal were utilized in the investigation.

Results:

We evaluated the expression of four key molecules (MB21D1, TMEM173, TBK1, and
IRF3) in the cGAS-STING pathway and found that the TMEM173 gene was significantly downregulated
in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Not only
immunostimulatory cells but also regulatory T cells were triggered by the DNA sensing pathway.
With gene enrichment analysis, we revealed that cell cycle and mechanotransduction/cytoskeleton
signals were most closely connected with cGAS-STING signal alterations in non-small-cell lung
cancer (NSCLC). cGAS-STING signaling was robustly correlated with methylation changes, especially
histone H3K4 lysine demethylase KDM5s. Transient activation of cGAS-STING was found
to exert tumor surveillance effect, and inhibition of STING signaling co-opt elevated KDM5 demethylases
might inadvertently worsen clinical outcomes.

Conclusion:

cGAS-STING signaling and KDM5 demethylases have the potential to be used as
targets for evaluating an effective immune response in the tumor microenvironment.
MIL-101(Cr)-Functionalized TEDA-BAIL: An Efficient and Recyclable
Catalyst for the Synthesis of Pyrimido[4,5-b]quinolinetrione Derivatives
Authors: Mahmoudi Zohreh , Kabirifard Hassan , Ghasemzadeh Mohammad Ali
Published: May 2022

Background:

In this study, a heterogeneous catalyst containing MIL-101(Cr) functionalized
TEDA-BAIL was used to carry out an efficient four-component reaction between aromatic aldehydes,
barbituric acid, dimedone, and aryl amines, resulting in the synthesis of a new class of pyrimido[
4,5-b]quinolinetrione derivatives.

Methods:

Pyrimido[4,5-b]quinolinetrione derivatives were synthesized through a one-pot fourcomponent
reaction between aromatic aldehydes, barbituric acid, dimedone, and aryl amines, in the
presence of triethylenediamine-based ionic liquid@MIL-101(Cr) composite as a catalyst under reflux
conditions. The TEDA-BAIL@MIL-101(Cr), which is a recyclable catalyst, was fully characterized
by Fourier transform infrared spectrophotometry (FT-IR), X-ray diffraction (XRD), scanning
electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) thermogravimetric analysis
(TGA), Brunauer-Emmett-Teller (BET) and Transmission electron microscopy (TEM).

Results:

Four-component synthesis of pyrimido[4,5-b]quinolinetriones was catalyzed by TEDABAIL@
MIL-101(Cr) with aromatic aldehydes, barbituric acid, dimedone, and aryl amines under
reflux conditions. The obtained experimental results revealed that the employed synthesis approach
is a simple method that offers several advantages, including sustainability, facile separation from the
reaction medium, and reusability of the catalyst after six consecutive runs without loss of activity.

Conclusion:

The presented method is an efficient synthesis route for the synthesis of pyrimido[4,5-
b]quinolinetriones in the presence of TEDA-BAIL@MIL-101(Cr) under reflux conditions. This procedure
provides multiple advantages, such as ease of execution, high yield, clean reaction conditions,
shorter reaction time, and catalyst sustainability.
The Functional Role of the Renin-Angiotensin System in Preeclampsia
Authors: Melaku Leta
Published: May 2022

The renin-angiotensin system (RAS) is a signaling pathway that acts as a major regulator
in human physiology. To sidestep the major intimidations of low blood volume and low blood pressure,
the diverse actions of Ang II/ACE/AT1R can be viewed as a useful response in maintaining
homeostasis. The deleterious action of the Ang II/ACE/AT1R axis is endogenously counterbalanced
by ACE 2/Ang 1-7/MasR. Yet, over activation of the Ang II/ACE/AT1R axis may lead to hypertension.
Preeclampsia is characterized by hypertension with proteinuria or end-organ dysfunction after
20 weeks of gestation. The early-onset sort is more genuine and capable of high maternal and fetal
dismalness and mortality rates than the late-onset sort of preeclampsia. Various theories for the
pathogenesis of preeclampsia are, the exact underlying molecular mechanisms remain unclear but
are likely to be multifactorial. Later studies of RAS in preeclampsia have highlighted the need for
thorough research on this topic. There is an increase in the levels of circulating angiotensinogen during
the first 20 weeks of gestation. At the beginning of the pregnancy, there is an increment of prorenin
by 4 - 5 times. Renin synthesis in preeclampsia is suppressed. PE pregnant women have higher
levels of prorenin receptor expression in their placental tissue than normal pregnant women. AT1
receptor autoantibodies are also observed. Ang II is raised in normal pregnancies as a result of higher
levels of angiotensinogen and renin. Preeclampsia causes a decrease in angiotensin-(1-7) levels.
Aldosterone is also relatively low in pregnancies complicated by preeclampsia.
The Prevalence of Maternal and Newborn Morbidity Following a Repeat
Cesarean Section: Data From Zagazig University Hospital
Authors: Ali Ali El-Shabrawy , Badr Amira I. , Mohamed El-Behairy Manal , Noseir Wael Sabry
Published: May 2022

Background and Objective:

Cesarean section (CS) is one of the most common obstetric procedures performed worldwide, and new research indicates that the frequency of CS is increasing. Maternal-fetal morbidity and death due to CS is a serious public health problem worldwide. Our study aimed to assess the impact of multiple cesarean sections (CSs) on mother-fetal morbidity.

Methods:

This cross-sectional study was performed on 165 women who underwent multiple repeated CSs in our clinic and met the criteria of inclusion by evaluating their records. All women were divided into 3 groups according to the number of CSs: 2nd (n = 111), 3rd (n = 44), and 4th/5th (n = 10). Maternal-neonatal outcomes; blood transfusion needs, adhesions, APGAR scores, and respiratory difficulties were investigated retrospectively.

Results:

Our results revealed that adhesion (60.6 %) was the most frequent maternal complication. The prevalence of thick adhesions decreased with the number of cesarean sections performed (70, 25, and 5 cases for the previous 2nd, 3rd, and 4 or more CS, respectively). There was no statistically significant difference between the groups in terms of adhesions, uterine rupture, bladder injury, endometritis, and wound infection. NICU admission (14.5 %), Low birth weight (3.6 %), and IUGR (3.03 %) were among the unfavorable fetal outcomes. There was a significant difference among the three studied groups regarding APGAR score, maternal age, and hospital stay, while a non-significance was found in birth weight and maternal adhesion.

Conclusion:

Our findings support our hypothesis that the likelihood of maternal complications rises as the number of CSs rises. The manner and time of delivery have a greater impact on infant outcome than the number of CSs. There is no clear absolute barrier for the number of CSs, however, 4 or more cesarean births were recognized as the essential level for the majority of outcomes. The number of CSs must be decreased to reduce the associated issues.
ECG for Cardiovascular Diseases Using Soft Computing Algorithms
Authors: Veer Karan , Mathur Prerak , Sharma Tanu
Published: May 2022

Electrocardiogram (ECG) is widely used in the healthcare domain because of its usage as a diagnostics tool for several cardiovascular diseases. It becomes essential to study and analyse the ECG data with the help of classification techniques. In this review paper, a brief overview of ECG signal information is presented. Various approaches for diagnosing cardiovascular diseases have been discussed, along with the need for accurate ECG signal analysis. These approaches are mainly based on the principles of machine learning and deep learning. The advantages and limitations of these techniques in the detection of cardiovascular diseases are presented within the scope of future work. This study can be helpful for researchers in bridging the gap between current approaches and future techniques for the detection of arrhythmia conditions.
Drug-aggravated Bullous Pemphigoid in a 47-year-old Asian Woman -
A Case Report
Authors: Nelramachandrakumar Divyajayashree , Hariharan Haritha , Nagamanickam Senthilvel , Chander J. Sam Johnson Udaya
Published: May 2022

Introduction:

Bullous pemphigoid is the most common chronic recurrent autoimmune
subepidermal blistering disorder most prevalent in the geriatric population. It varies widely in clinical
presentation ranging from tense bullae to intense generalized pruritus. It is immunologic in
origin with the presence of IgG antibodies.

Case Report:

A 47-year-old female presented to the hospital with complaints of blisters in the lower
limbs, which she self managed with neem oil, after which the blisters occurred over the body.
The patient also experienced blisters over both upper and lower limbs, gluteal region, painful generalized
ulcers, necrotic patches, multiple erythematous blisters, ulcer erosions over bilateral legs
and upper limbs with few lesions, which were foul-smelling and oozing. On the second day of admission,
the patient’s CRP and ESR levels were tested and the levels were 33.5 and 35 mm/hr, respectively.
The patient was treated with an injection of meropenem 1 g three times daily, dexamethasone
4 mg once daily, and ofloxacin 400 mg once daily. On the third day of admission, the patient
complained of leg swelling, and subsequently, D-Dimer levels were checked, which showed a
value of 5,740 and was treated with an injection of enoxaparin 40 mg for the same throughout the
course of the hospital stay A skin biopsy confirmed the diagnosis of bullous pemphigoid. The culture
test showed the growth of Klebsiella pneumonia and Acinetobacter baumani, which were resistant
to most of the antibiotics. The patient was managed appropriately with modalities including
antibiotics, anti-inflammatory agents, immunosuppressants, multivitamins, fluids, and albumin.
The patient responded well to the treatment without new lesions or fever spikes. There was the
presence of necrotic patches of old lesions alone at the time of discharge.

Conclusion:

This case report was done with the purpose of presenting an exemplary case of
bullous pemphigoid aggravated by the application of neem oil and emphasizing the inappropriate
use of folk medicine in an autoimmune disease like bullous pemphigoid.
Reactivity of 9-anilinoacridine Derivatives as Potent Anticancer
Agents: A DFT Approach
Authors: Sarmah Pubalee , Deka Ramesh Chandra
Published: May 2022

Background:

Anticancer activity of 9-anilinoacridine derivatives has been well
reported. Although, the DNA-drug sequence-specific binding of these compounds may be
affected by the substituent(s) on the aniline ring, it is still unclear which substituent (NH2
or CH2–OH) on the anilino ring of the compound is the critical element. A good understanding
of chemical properties such as steric, lipophilic and electronic properties at the molecular
level may provide important background for mutagenic and carcinogenic properties.

Objectives:

The present study is an attempt to understand the reactive nature of some selected
9-anilinoacridine derivatives in both gas and solvent phases and to predict their anticancer
activity by QSAR analysis.

Methods:

Full geometry optimizations of all derivatives were carried out at gradient corrected
DFT using DMol3 program. We used DNP basis set in combination with BLYP to
study all the derivatives. The molecular mechanics parameters used for QSAR analysis
were calculated using Hyperchem software.

Results:

We found Compound (31) (R=COOC6H5) as the most stable compound and compound
(6) (R1= NO2) as the most reactive one in both gas and solvent phases. Fukui function
(f+) values of all the atoms showed that N10 is the most reactive atom in each of the molecule
which indicates that N10 is the preferred site for nucleophilic attack. The final QSAR
model with four parameters (electrophilicity, hardness, surface area, and molar refractivity)
is capable of predicting anticancer activity of the compounds against leukemic HL-60 cell
lines with r2 = 0.91 and 0.88 in both gas and solvent phases, respectively.

Conclusion:

The global and local reactivity descriptors, such as hardness, chemical potential,
electrophilicity index, Fukui function, and local philicity were calculated to understand
the reactive nature and reactive sites of the compounds. The comparative QSAR study
with the help of DFT and MM + techniques provides the importance of the selected descriptors
in predicting the activity of the selected derivatives.
Molecular Modelling and Docking Analysis of Filarial Targets by using New Lead Compounds identified fromPsoralea corylifoliaandMimusops elengi
Authors: A. Shobana , A.M. Priyadharshini , Manoharan Yogalakshmi , Bagavananthem Andavan Gowri Shankar
Published: May 2022

Background:

Psoralea corylifolia and Mimusops elengi could be a source of new bioactive compounds for treating filariasis Psoralea corylifolia and Mimusops elengi. Thediversity of these plants has been proved medicinally and phytochemically. These plants haveplayed an important role in ancient medicine for the treatments of various ailments and especially against many helminths.

Methods:

Psoralea corylifolia and Mimusops elengi could be a source of new bioactive compounds for treating filariasis. 20g of dried powder of Psoralea corylifolia and Mimusops elengi were extracted using a Soxhlet apparatus using various solvents like methanol, chloroform, acetone, and water for about 30 cycles and then concentrated using a rotary evaporator and stored at 4 °C in airtight containers. It is effective against Setaria cervi at 100 and 200 μg, respectively. In-vitro studies have been done for the respective compounds. Homology models of Glutathione S transferase, Chitinase, and Transglutaminase were constructed using MODELLER v9.20 (Accelrys).

Results:

The results from the in vitro studies were confirmed by TLC and GC MS analysis of the extracts, which showed the presence of different phytochemical compounds in the extracts. Among the compounds identified in GC MS, 7,10-Octadecadienoic acid, methyl ester, Pentadecanoic acid, 14-methyl-, methyl ester, 2-Nonadecanone2,4-dinitrophenylhydrazine, Aspidospermidin-17-ol, 1- acetyl-19,21-epoxy-15,16-dimethoxy-, 9- (2’,2’-Dimethylpropanihydrozano)-3,6 dichloro-2,7-bis- [2-(diethylamino)-ethoxy] fluorine, and 2,2,4-Trimethyl-3-(3,8,12,16-tetramethyl-heptadeca- 3,7,11,15-tetraenyl)-cyclohexanol were docked against crystallised bioactive compounds.

Conclusion:

As a result of this study, it was concluded that arresting these proteins will help in arresting the growth and multiplication of parasites, thus leading to the development of a new antifilarial drug.
SARS-CoV-2 Kerala Isolate Spike Protein Induces Cancer Proliferating
Markers for Lung and Breast Cancer: An In Silico Approach
Authors: Selvaraj Stalin , Chandrasekaran Deepak , Masimani Vinothini , Ravindrana Yazhiniv , Venugopal Gayathriv , Raghavendran Srikanth
Published: May 2022

Background:

Coronavirus disease (COVID 19) has been emerging as a major threat to humans
all over the world. Severe Acute Respiratory Syndrome CoronaVirus 2 (nSARSCoV2) is the causative
agent for the disease resulting in severe acute respiratory illness. Earlier, it took several years to come up
with a vaccine or other sorts of treatments for viral diseases. But now with the advent of biotechnology
and development of bio-informatic tools, the process has been accelerated. The WHO reports 39,806,488
affected cases and 1,112,208 deaths till today all over the world (17 Oct 2020). nSARS CoV2 has a greater
influence on people with comorbidities mainly cancer.

Objective:

The study herein attempts to understand the binding affinity of the spike protein of the novel
coronavirus with the lung and breast cancer marker proteins by docking and ClusPro analysis.

Method:

The analysis was conducted in reference to hACE2 (human Angiotensin Converting Enzyme
2), the receptor of nSARS CoV2. Total 22 different marker proteins were analyzed using ClusPro.

Results:

BRCA1 (Breast Cancer type 1 susceptibility protein) and CXCR4 (a chemokine receptor belonging
to the G protein coupled receptor family) were found to exhibit higher binding affinities.-73.82
kcal/mol and -66.45 kcal/mol were the global energies they showed upon binding to S protein respectively.

Conclusion:

Therefore, novel SARSCoV2 has a higher chance of inducing cancer in non-cancerous individuals
and aids in cancer acceleration in cancer patients . This poses a threat to cancer patients and immunocompromised
individuals. The study can be exploited to identify the optimal drug delivery system
for novel SARS CoV2.
utilization of shredded snakehead fish in an effort to prevent stunting in children in Palangka Raya
Authors: Mahalia Lamia Diang , Ramadhani Juni
Published: May 2022

Background: Children need adequate nutrition intakes to avoid stunting. One thing that we can do is by giving them an adequate protein intake. Snakehead fish is one of the foodstuffs that have a high protein composition. Objective: This study was carried out in an effort to improve the nutritional status of children to avoid stunting by using snakehead fish which is processed into shreds (commonly called shredded fish). Methods: This study used a post-test only design approach with a control group. The subjects of this study were 30 children with inclusion criteria: subjects were in good health, aged 36-72 months, could receive an oral diet, could consume shredded fish and fish, and had no history of protein allergy. Children were given lunch with a side dish of shredded snakehead fish continuously for 30 days.Results and discussion: Shredded fish that produced is using snakehead fish has a brownish yellow color and is dry, fibrous, crunchy and tasty. Shredded Snakehead fish, which is consumed regularly for 30 days, can improve the nutritional status of children.