bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of groove configuration on mechanical properties and fracture behavior of 6061 Al alloy and CFRTP laser joint
Authors: Liu Xing , Wang Jianfeng , Bu Hengchang , Wang Feiyun , Zhan Xiaohong
Published: May 2022

Laser surface texturing is generally a promising approach to enhance the adhesion property of metal-thermoplastic hybrid structure, and the effect is related to the groove configuration. Laser joining of carbon fiber reinforced thermoplastic composite (CFRTP) to 6061 Al alloy under various groove configuration was carried out, aimed to investigate the effect of groove width and depth on interfacial morphology, mechanical properties and fracture behavior of CFRTP/ Al joints. The tensile-shear force was tested, and the fracture surface and interface morphology were observed by scanning electron microscopy. Besides, the numerical simulation of temperature field was conducted to reveal the joining mechanism. The results indicate that the tensile shear strength of CFRTP/ Al joint gradually increases with the increase of groove width and reaches the peak value of 22.8 MPa when the width is 0.5 mm, then it decreases as the groove width is further increased. Compared to groove width, the tensile shear strength of CFRTP/ Al joint presents similar variation trend with the increasing groove depth on Al alloy surface. When the groove depth reaches 0.6 mm, the maximum joint strength is 24.33MPa. After laser textured Al alloy, the surface fracture mode of CFRTP/Al laser joint features mixed fracture mode including cohesive fracture and interface fracture. This study provides a deeper understanding of the effect of groove configuration on the laser joining of CFRTP/ Al hybrid structure and potentially lays a foundation for the adjustment of suitable groove configuration toward obtaining the desired effect.
1-Aryl-1,2,3,4-tetrahydro-isoquinolines inhibit TNFR2-mediated proliferative expansion of CD4+Foxp3+ regulatory T cells
Authors: Chen Fengyang , Geng Chang-An , Zheng Jinbing , Li Tian-Ze , Yang Yang , Wang Yi-Fei , Li Ping , Jiang Meng-Meng , Li Yuan , Chen Ji-Jun , Chen Xin
Published: May 2022

Tumor-infiltrating CD4+Foxp3+ regulatory T (Treg) cells express high levels of TNFR2 which mediates TNF-induced proliferation and promotes tumor progression by suppressing anti-tumor immune responses. Therefore, the blockage of TNF-TNFR2 pathway represents a strategy to eliminate tumor-infiltrating Treg activity and leads to the recovery of host immune responses against tumor. In this study, screening of in-house small-molecule library resulted in the identification of 1-aryl-1,2,3,4-tetrahydro-isoquinolines as potent inhibitors of Treg proliferation mediated by TNF-TNFR2 signaling. Moreover, in-depth analysis of structure-activity relationship (SAR) revealed that the 6,7-dimethoxylation and 1-naphthyl substitution could improve the activity. Therefore, further investigation is warranted to evaluate if 1-aryl-1,2,3,4-tetrahydro-isoquinolines could be used as adjuvants to enhance cancer immunotherapy.
Menopause Rating Scale (MRS) in Bahasa Melayu language- Translation and Validation In Multiethnic Population In Malaysia
Authors: Mathialagan Sashimalar , Ramasamy Shamala , Nagandla Kavitha , Fern Siew Wei , Sreeramare Chandrashekhar T
Published: May 2022

Background
The menopause Rating Scale (MRS) is an internationally used tool to measure menopause-related symptoms to date and is unavailable in the Bahasa Melayu language. We aimed to translate and validate the Bahasa Melayu version of the MRS.
Methods
Translation of the English version of MRS into Bahasa Melayu was done by a bilingual expert and back-translated. Bahasa Melayu MRS was reviewed by a panel to determine the face validity. A total of 321 women aged 40–60 years residing in Klang, Selangor, Malaysia were selected by stratified random sampling method in a house-to-house survey. The Bahasa Melayu MRS was self-administered. Reliability analyses, including test-retest reliability (on 30 women after a two-week interval) were conducted. To ascertain the construct validity, 11 items were analyzed using exploratory factor analyses to determine the factor structure. To further support the psychometric study, confirmatory factor analysis was conducted to evaluate the structural model fit of Bahasa Melayu MRS.
Results
A total of 294 (91.6%) completed the survey and their mean age was 50.9 years (SD = 6.3). An overall Cronbach’s alpha for MRS was 0.904. Cronbach’s alpha for psychosomatic, urogenital, and Somatovegetative subscales were 0.889, 0.846, and 0.776 respectively. The corrected item correlations were approximately 0.6 and inter-item correlations were between 0.3 and 0.9. Assumptions for exploratory factor analyses were not violated; Kaiser–Meier–Olkin test revealed a value of 0.883 and Bartlett’s test value of sphericity was statistically significant (χ2 = 2400.483 and p < 0.001). EFA identified three factors accounting for 51.4% of the variance. This study encountered straddling of items. EFA yielded all 4 psychological items in Factor 2. The items which are supposedly falling into Somatic-Vegetative and Urogenital domains are straddled in Factor 1. Two items (heart complications and bladder problems) are grouped in the 3rd Factor. Nevertheless, confirmatory factor analyses showed a good model fit, fitting well into the theoretical constructs.
Conclusion
The translated English version of the Menopause Rating Scale into the Bahasa Version showed excellent reliability, test-retest reliability, and construct validity. The instrument can be used to assess menopause-related symptoms among Malaysian women.
Antenatal and perinatal healthcare delivery associations with Infant and Young Child Feeding (IYCF) breastfeeding practice in Nepal: a population-based cross-sectional study
Authors: Hollow Breanna Louise , Bulsara Max K. , Pant Prakash Dev , Wallace Hilary Jane
Published: May 2022

Background Infant and Young Child Feeding (IYCF) breastfeeding guidelines of the World Health Organization (WHO) have been promoted in Nepal since the early 1990s. This study investigated whether antenatal and perinatal healthcare delivery in Nepal were associated with breastfeeding within one hour of delivery and age-appropriate IYCF breastfeeding practice (exclusive breastfeeding to six months; continued breastfeeding to two years).Methods Data from the 2016 Nepal Demographic and Health Survey (NDHS) were analysed using multivariable logistic regression. The unit of analysis was an interviewed woman and her last-born child aged 0–23 months. Healthcare delivery components examined were four completed antenatal visits, place and type of delivery, infant-mother skin-to-skin contact post-delivery, and breastfeeding observation and counselling within two days post-delivery.Results Of 1938 mother-infant dyads, 1073 (55.4%) commenced breastfeeding within one hour of delivery and 1665 (85.9%) were engaged in age-appropriate breastfeeding. Breastfeeding within one hour of delivery was associated with infants delivered vaginally (aOR: 4.76, 95% CI: 2.96–7.65), mothers who were observed breastfeeding by a health professional (aOR: 1.58, 95% CI: 1.20–2.08) and early skin-to-skin contact (aOR:2.10, 95% CI: 1.63–2.72). Age-appropriate breastfeeding was lowest amongst those with children aged 4–5 months (40.8%) compared to women with infants aged 0–1 month (aOR: 0.158, 95% CI: 0.083–0.302). Antenatal and perinatal healthcare delivery were not significantly associated with age-appropriate breastfeeding.Conclusion Further promotion of early skin-to-skin contact and the observation of early breastfeeding practice, including after caesarean births, may increase early initiation of breastfeeding. Additional support, including postnatally, is necessary to increase exclusive breastfeeding of infants 4–5 months of age.
Lupane Derivatives: Design, Isolation, Synthesis and anti-malarial activity against Plasmodium falciparum 3D7 strains.
Authors: Yemback Pierre , Oben Eyong Kenneth , Efange Noella , Kamdem Michael HK , Ndinteh Dereck T , Odumosu Patricia O , Folefoc Gabriel N , Ayong Lawrence , Werner Thomas
Published: May 2022

To search for leads against malaria, compounds from the Cameroon Natural Product Library (CANAPL), were screened by molecular docking studies against the enzyme target Glyceraldehyde-3-phosphate dehydrogenase (PfGAPDH) for Plasmodium falciparum. Amongst these docking hits were the lupeol cinnamate (1) and oleanane cinnamate (2). Triterpenoids with structural similarities to (1) and (2) were isolated from Baillonella toxisperma (Pierre); olean-12-en-3β-hexadecanoate (3), 3-β-trans cinnamoyloxylup-20(29)-ene (4), oleanoic acid benzoate (5), 3β-amyrin (6), taraxerol (7), betulonic acid (8), β-sitosterol (9), betulinic acid (10), 3β-(trans-p-Coumaroyl)oxylup-20(29)-en-28-oïc acid (11), and screened alongside Betuline (12) and oleanolic acid (13). The favorable compounds 8 and 11 with 100% growth inhibition on Plasmodium falciparum 3D7 strains together with compounds 4, 10 and 12 were structurally optimized to afford new lupane derivatives with the privilege α-β unsaturated carbonyl medicinal scaffolds; betulonic acid acryl aldehyde (14), betulin acryl aldehyde (15), 3β-(trans-p-Coumaroyl)oxylup-20(29)-en-28-oïc acid acryl aldehyde (16), betulinic acid acryl aldehyde (18) and 3-β-trans cinnamoyloxylup-20(29)-ene acryl aldehyde (19) exhibiting more potent anti-malarial activities with IC50 values of 0.703 µM, 2.15 µM, 1.28 µM, and 3.79 µM for compounds 14, 15, 16 and 18 respectively. The modified compounds with the privilege α, β-unsaturated carbonyl medicinal scaffolds could be further optimized into potent antimalarial agents.
A practical “low-carbohydrate dietary care” model for elderly patients with type 2 diabetes
Authors: Feng Yuwei , Wang Qinyue , Hua Jiao , Liu Yiran , Zhong Xiaohui , Cao Hong , Xia Yanping , Zhang Feng
Published: May 2022

A randomized, double-blind, controlled experiment was conducted to observe how dietary care with restriction of carbohydrate absorption affects glucose and lipid metabolism in elderly patients with type 2 diabetes. Participants in the control group (Group C) were given standard treatment and in the experimental group (Group E) white common bean extract (WCBE) was given before meals. The trial was divided into two periods: intensive and maintenance intervention periods. Glucolipid metabolism was monitored in both groups during two intervention periods. Glycosylated hemoglobin (HbA1c) in Group E was lower than in Group C at the end of the 2- and 4-month, and significantly decline from baseline. The area under curve of oral glucose tolerance test (OGTT) glucose after 2- and 4-month intervention than baseline in Group E and were all significantly lower than in Group C after the intervention. Both High-density lipoprotein (HDL) and Low-density lipoprotein (LDL) also improved in group E (P < 0.05). In the clinical management of elderly patients with type 2 diabetes, this individualized model of care without restricting carbohydrate intake can effectively improve patients' glucose metabolism. The effect of this care model is similar to that of a low-carbohydrate diet care model. Therefore, this regimen could be a novel antidiabetic approach for patients with type 2 diabetes who are unwilling to restrict their carbohydrate intake.
ToxTree: Descriptor-based machine learning models to predict hERG and Nav1.5 cardiotoxicity
Authors: Arab Issar , Wonneberger Daniela , Barakat Khaled
Published: May 2022

Drug-mediated blockade of the voltage-gated potassium channel(hERG) and the voltage-gated sodium channel (Nav1.5) can lead to severe cardiovascular complications. This rising concern has been reflected in the drug development arena, as the frequent emergence of cardiotoxicity from many approved drugs led to either discontinuing their use or, in some cases, their withdrawal from the market. Here, we introduce two robust 2D descriptor-based QSAR predictive models for both hERG and Nav1.5 liability predictions. The machine learning models were trained for predicting the potency to each channel using multiclass classification at three different potency cut-offs (i.e. 1µM, 10µM, and 30µM). The ToxTree-hERG Classifier, a pipeline of Random Forest models, was trained on a large curated dataset of 8380 unique molecular compounds. Whereas ToxTree-Nav1.5 Classifier, a pipeline of kernelized SVM models, was trained on a large manually curated set of 1550 unique compounds retrieved from both ChEMBL and PubChem publicly available bioactivity databases. The hERG model yielded a multiclass accuracy of Q4 = 74.5% and a binary classification performance of Q2 = 93.2%, sensitivity = 98.7%, specificity = 75%, MCC = 80.3%, and a CCR = 86.8% on an external test set of N = 499 compounds. The proposed hERG inducer outperformed most metrics of the state-of-the-art published models and other existing tools. Additionally, we are introducing the first Nav1.5 liability predictive model achieving a Q4 = 74.9% and a binary classification of Q2 = 86.7% with MCC = 71.2% and F1 = 89.7% evaluated on an external test set of 173 unique compounds.
A Pan-Cancer Analysis of prognosis and immunity of cuproptosis-related gene FDX1
Authors: Ma Siyuan , Hu Die , Zhu Ping , Zhang Bochao , Zhang Yanzheng , Zhao Xiaoxiao , Pu Chun
Published: May 2022

Purpose FDX1 is a key gene regulating cuproptosis, but there is no pan-cancer analysis. We performed a pan-cancer analysis of FDX1 using bioinformatics techniques to derive the effect of FDX1 on the immune mechanisms and prognostic value of cancer patients.Methods We comprehensively investigated the expression profile of FDX1 using the Timer, TCGA, and GTEx databases, we established Cox proportional hazards regression models to evaluate the prognostic value of FDX1. cBioPortal database was used to study the frequency of changes and mutations of FDX1, the ULCAN database for FDX1 phosphorylation, sites, and using GSCA database to investigate the FDX1 DNA methylation in different cancers. The effect of FDX1 on immune mechanisms in various types of cancers was investigated. FDX1-related genes were collected using the gepia database, we performed GO enrichment and KEGG pathway analysis on FDX1 and FDX1-related genes, and single-gene GSEA pathway analysis was performed. We used String database to draw the Protein-Protein Interaction Networks of FDX1.Result FDX1 expression showed a significant downward trend in most tumors and was strongly associated with prognosis in some tumors. We observed elevated phosphorylation levels at the S177 site of KIRC or LUAD and decreased phosphorylation levels at the S159 and S177 sites of LIHC. There is a certain correlation between FDX1 DNA methylation and mRNA expression which related to the prognosis of the tumors. The proportion of immune cells in each tumor was essentially the same except for UVM. In LGG, KIRP and THCA, FDX1 expression was significantly correlated with immune infiltrating cells, it was significantly correlated with the levels of most immune-related genes. The correlation between FDX1 and TMB and MSI may provide a basis for drug use in certain tumors.Conclusion FDX1 can be used as a prognostic marker for some tumors.
Liver-to-portal vein ratio for evaluating liver function in Gd-EOB-DTPA-enhanced Magnetic Resonance Imaging: what we should know?
Authors: Wang Chao , Yuan Xiaodong , Wu Ning , Sun Weirong , Tian Yuan
Published: May 2022

Background
To investigate the clinical value of liver-to-portal ratio (LPR) on adequate hepatobiliary phase (HBP) defined by 2016 Gastrointestinal and Abdominal Radiology (ESGAR) consensus statement to assess liver function.
Methods
Between March 2020 and February 2022, a total of 115 subjects with liver disease were referred by physicians for Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) were prospectively enrolled in the study. Eighty of the 115 subjects were cirrhotic, then all subjects were divided into 4 subgroups according to Child-Pugh (C-P) classification (non-cirrhosis: 35, C-P A: 30, C-P B: 35, C-P C: 15). Two radiologists used 4-point scale to determine the adequate HBP for all subjects, and the LPR on adequate HBP was calculated by other two radiologists. Spearman rank correlation coefficient was used to analyze the correlation between C-P classification and LPR on adequate HBP. The differences in delay time and LPR on adequate HBP among four subgroups were analyzed by One-way ANOVA and Dunnett’s multiple comparisons. Intraclass correlation coefficient (ICC) and κ-statistics were used to test the consistency of measurements and HBP adequacy between radiologists, respectively.
Results
The correlation between the delay time of adequate HBP and liver function was positive (r = 0.802, P < 0.01), while the LPR decreased with severity of cirrhosis (r = -0.562, P < 0.01). the difference in delay time and LPR were significant among four subgroups (P < 0.01), however, the LPR on adequate HBP between C-P B subgroup and C-P C subgroup wasn’t statistically significant (P > 0.05). ICC = 0.93 (95%Cl: 0.92–0.94) and κ-value (0.87) demonstrated that the measurements and interpretation of HBP were good between radiologists.
Conclusions
Prolonged delay time benefits patients with cirrhosis to obtain adequate HBP, and the LPR decreases with the severity of cirrhosis, however the downward trend of LPR is attenuated with more severe liver impairment. The efficacy of LPR on adequate HBP to assess moderate-to-severe cirrhosis decreased.
Effect of UV-C treatments followed by storage on the storability characteristics of sesame (Sesamum indicum) seeds
Authors: Hassan. Amro
Published: May 2022

In this study, UV-C doses 0, 2.5, 5.0 and 10 kJ.m− 2 were applied to investigate the changes in the storability characteristics during the storage of sesame seeds. The fungal growth, aflatoxin content, water activity, colour parameters (L*, a*, b* values, and ΔE) and free fatty acid content were evaluated. The fungal growth, water activity, and L* values were found less in the UV-C treated sesame than in control samples in both fresh and stored samples. However, these doses increased (p < 0.05) a* and b* values and the free fatty acid of the sesame seeds. The Partial Least Squares regression analysis stated that the application of 5.0 kJ.m− 2 followed by 6 months of storage reflects the most valid treatment doses for UV-C treatments of sesame seeds. Consequently, potentially afford effective and rapid quarantine security as an alternative to chemical fumigation protocol to extend the shelf life and enhance the storability characteristics of sesame seeds.
Prognostic impact of pretreatment T790M mutation on outcomes for patients with resected, EGFR-mutated, non-small cell lung cancer
Authors: Matsumoto Yoshiya , Kawaguchi Tomoya , Watanabe Masaru , Isa Shun-ichi , Ando Masahiko , Tamiya Akihiro , Kubo Akihito , Kitagawa Chiyoe , Yoshimoto Naoki , Koh Yasuhiro
Published: May 2022

Background: Many previous studies have demonstrated that minor-frequency pretreatment T790M mutation (preT790M) could be detected by ultrasensitive methods in a considerable number of treatment-naïve, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) cases. However, the impact of preT790M in resected cases on prognosis remains unclear.Methods: We previously reported that preT790M could be detected in 298 (79.9%) of 373 surgically resected, EGFR-mutated NSCLC patients. Therefore, we investigated the impact of preT790M on recurrence-free survival (RFS) and overall survival (OS) in this cohort by multivariate analysis. All patients were enrolled from July 2012 to December 2013, with follow-up until November 30, 2017.Results: The median follow-up time was 48.6 months. Using a cutoff value of the median preT790M allele frequency, the high-preT790M group (n=151) had significantly shorter RFS (hazard ratio [HR]=1.51, 95% confidence interval [CI]: 1.01-2.25, P=0.045) and a tendency for a shorter OS (HR=1.87, 95% CI: 0.99–3.55, P=0.055) than the low-preT790M group (n=222). On multivariate analysis, higher preT790M was independently associated with shorter RFS (high vs low, HR=1.56, 95% CI: 1.03-2.36, P=0.035), irrespective of advanced stage, older age, and male sex, and was also associated with shorter OS (high vs low, HR=2.16, 95% CI: 1.11-4.20, P=0.024) irrespective of advanced stage, older age, EGFR mutation subtype, and history of adjuvant chemotherapy.Conclusions: Minor-frequency, especially high-abundance of, preT790M was an independent factor associated with a poor prognosis in patients with surgically resected, EGFR-mutated NSCLC.
Ascophyllum nodosum algae-based biostimulant mitigates heat stress in soybean
Authors: Repke Rodrigo Alberto , Silva Dayane Mércia Ribeiro , Santos Jania Claudia Camilo dos , Silva Marcelo de Almeida
Published: May 2022

Heat stress is one of the environmental factors that most limit soybean productivity (Glycine max (L.) Merrill). The use of biostimulants based on Ascophyllum nodosum (L.) seaweed extract can mitigate the effects of heat stress. Therefore, the effects on the morphological, physiological, biochemical and productive variables of soybean grown at high temperature and under exogenous application of biostimulant based on seaweed was investigated in this research. The results showed that the application of 1 L ha-1 of the biostimulant increased the tolerance of soybean plants to heat stress, as it increased the rate of CO2 assimilation, stomatal conductance, the rate of transpiration and carboxylation efficiency, in addition to reducing leaf temperature, but did not influence the efficiency of water use and relative chlorophyll content (SPAD index). In addition, the application of the biostimulant increased the activity of the antioxidant enzymes superoxide dismutase, catalase and ascorbate peroxidase; and maintained the activity of peroxidase and reductase nitrate, as well as the proline concentration. Furthermore, the foliar application of the biostimulant improved the biometric and production characteristics, resulting in greater productivity. Based on these beneficial properties, the biostimulant based on algae extract at a dose of 1 L ha-1 proved to be effective in alleviating the adverse effects of heat stress in soybeans.
External application of human umbilical cord-derived mesenchymal stem cells in hyaluronic acid gel repairs foot wound of type I and type II diabetic rats through paracrine action mode
Authors: Chen Jingan , Liu Yi , Zhang Jingwen , Liang Haowei , Li Ting , Yan Li , Zhou Li , Shan Letian , Wang Hui
Published: May 2022

Background: Diabetic foot ulcer (DFU) is a main complication of diabetes mellitus with high rate of amputation and low rate of therapeutic success. External application of mesenchymal stem cells (MSCs) provides a new therapeutic option to treat DFU and avoids the drawbacks of injective MSCs therapy. In this study, human umbilical cord-derived MSCs-hyaluronic acid gel (hucMSCs-HA gel) was developed for evaluating the external efficacy of MSCs on DFU, and its paracrine mode of action was explored by using hucMSCs-conditional medium (MSC-CM). Methods: In vivo, type I and type II diabetic rat models were established and received hucMSCs-HA gel external treatment, and histopathological staining (HE and Masson) and immunohistochemical analysis were conducted. In vitro, human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs) were exposed to high glucose and received MSC-CM treatment, and the assays of cell viability, wound healing, transwell migration, tube formation, cell senescence, reactive oxygen species (ROS), malondialdehyde (MDA) detection, qRT-PCR, and Western blot were conducted. The in vivo data indicated that hucMSCs-HA gel accelerated DFU healing in both type I and type II diabetic rats by improving re-epithelialization, collagen deposition, and angiogenesis, in which hucMSCs played a major role in the gel. Results: The in vitro data demonstrated that MSC-CM not only improved cell viability, wound healing, migration, tube formation, and cell senescence of HUVECs, but also promoted cell viability, accelerated wound healing, and reduced ROS and MDA production of HSFs, suggesting a paracrine mode of action of hucMSCs in treatment of DFU. Moreover, MSC-CM significantly restored the abnormal expressions of pro-inflammatory and antiangiogenic genes (TNF-α, IL-1β, IL-6, ET-1 and p16) and proliferative protein (PCNA) of HUVECs, and also restored the pro-fibrotic and antioxidant genes (COL1A1, COL3A1, COL4A1, SOD1 and SOD2) and proteins (PCNA and COL1) of HSFs. Conclusions: These results suggested that hucMSCs-HA gel facilitated DFU healing of type I and type II diabetic rats mainly through paracrine actions on HUVECs and HSFs. This study provided new insights into MSCs therapy and a promising therapeutic strategy for the clinical treatment of DFU.
A nomogram for predicting node-positive disease in muscle-invasive bladder cancer
Authors: Wu Jie , Shang Bingqing , Xie Ruiyang , Guan Youyan , Bi Xingang , Shou Jianzhong , Shi Hongzhe
Published: May 2022

Background: Non-metastatic muscle-invasive bladder cancer (MIBC) with lymph node (LN) metastasis is an aggressive disease with a poor prognosis. This study aimed to investigate risk factors for node-positive disease (pN+) and develop a nomogram to predict the likelihood of LN metastases in MIBC patients using a large population-based cancer database. Methods: Data of all patients with non-metastatic MIBC from 2004 to 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and analyzed retrospectively. Logistic regression analyses were used to identify independent risk factors of pN+ to develop nomogram. Predictive nomogram was carried out with R software to identify the LN involvement. The performance of the nomogram model was evaluated by calibration slope and receiving operating characteristic (ROC) curve. Results: A total of 12,269 non-metastatic MIBC patients in the SEER database were included. Larger tumor size, overlapping lesion, young age, female, poorly differentiated histological grade, and advanced T stage, are independent risk factors for pN+. We integrated the above variables into the models. The area under the curve (AUC) of ROC curve was 0.704. We separated non-metastatic MIBC patients into three groups according to the risk classification system of the likelihood of LN metastases, in which intermediate or high risk for LN metastases might not be good candidates for bladder preservation. Conclusions: We performed the first accurate nomogram with clinical and oncological variables for LN involvement of non-metastatic MIBC patients, which might help clinicians in patient risk stratification and outcome estimation.
Enablers and Barriers to Adequate Complementary Feeding (CF) Practices in Pakistan; Secondary Analysis of Formative Research on National CF Assessment (NCFA)
Authors: Shuja Saba , Khan Wisal , Mahmood Hana , Kiani Hira , Sheraz Syed Yahya , Ategbo Eric Alain
Published: May 2022

Background
Malnutrition among children continues to be one of the major public health problems globally with majority of cases residing in Asia. Within this region, Pakistan is among the countries with the highest burden of child malnutrition as 28.9% children are underweight, 40.2% are stunted and 17.7% suffer from wasting. Among the key contributors towards malnutrition in early years of life, inappropriate breastfeeding and complementary feeding (CF) practices are most appropriate There is a need to explore the factors responsible for poor feeding practices to address the gaps for designing evidence-based interventions focusing on social, cultural, and economic aspects of CF practices.We, therefore, aimed to understand how the cultural and social context in Pakistan influences the CF practices and the key social, cultural and economic drivers of change that need to be considered when shaping future policies and development interventions.
Methods
We conducted secondary analysis on the qualitative data collected through formative research as a part of the National CF Assessment (NCFA) conducted in 2018 across Pakistan by United Nations Children’s Fund (UNICEF) and the Pakistani Ministry of National Health Services, Regulation and Coordination (MoNHSR&C). In-depth interviews and focus group discussions conducted with mothers and fathers of children aged 6 to 23 months were included in the analysis. Framework analysis approach was applied to analyze the data.
Results
Financial barriers included limited finances and unemployment of the father, cultural barriers included restricted female mobility, heavy workload on mothers and dietary misconceptions whereas large family size, inaccess to food, inadequate knowledge and poor perception on CF, use of shelf foods, preference of child to certain foods, and harsh environmental conditions were reported as social barriers. Financial enablers included sound economic conditions of the household whereas joint family system, multiple sources of income, kitchen gardening, home based poultry, counseling by lady health workers and health care providers were among the social enablers.
Conclusion
Considering CF practices in Pakistan are inadequate therefore strategies are to be put on removing barriers to adequate CF. This can only be achieved if efforts are indicated from the policy level down to the community.
Prescription Practices and Rational drug use in a tertiary care teaching hospital using the World Health Organization core drug use indicators: A prospective pilot study.
Authors: Chenchula Santenna , G Rupesh , R Padmavathi , G Sunilkumar
Published: May 2022

Introduction: Rational drug prescribing is an important aspect of drug prescribing which helps in safe and efficacious and cost-effective drug treatment to patients. WHO Prescription indicators are intended to evaluate the services provided to the population concerning rational use of medicines.To study the prescription practices and rational drug use in the department of Internal medicine, using the WHO prescribing indicators in a tertiary care teaching institute of national importance,Methods and Material: The present OPD based prescription audit pilot study was carried out in the department of internal medicine, in an institute of national importance, Central India.A total of 50 prescriptions were digitally photographed and analysed for prescription practices and rational drug use, using standard WHO core prescribing indicators. A total of 301 drugs with multiple and diverse diagnoses. Statistical analysis was done using SPSS 22 version.Results: The average number of drugs per prescription was 3.48%. It was found that only 13.79% of prescriptions have generic names, whereas 27.58% of patient encounters had at least one drug from the NLEM, 6.8% of prescriptions have antibiotics and 0.7% prescriptions were injections. The number of prescriptions with FDC was 27.55%. Conclusion: Many prescriptions were not met the WHO core drug indicators criteria in EML, FDC and also in prescribing with the generic name. Hence, we will suggest regular prescription audit practices and conducting CMEs and training workshops for clinicians for rational use of medicines in all healthcare settings to succeed in the rational use of medicine.
Visceral adipose index as a predictor of new-onset diabetes and cardiovascular events in a geriatric community
Authors: Liaw Fang yih , Pei Dee , Chen Yen Lin , Kao Tung Wei , Chen Fang Yu , Huang Li Ying
Published: May 2022

BackgroundAbdominal obesity presents a higher risk of developing diabetes and future cardiovascular events. The Visceral Adiposity Index (VAI) can be an indicator of adipose distribution and function. This study aimed to evaluate VAI as a predictor of new-onset T2DM and cardiovascular events in the geriatric population.MethodCommunity-dwelling elderly adults ages 60–80 received regular health examinations in a privately owned chain of clinics in Taiwan between 1999 and 2008. VAI was calculated with anthropometric measures and biochemical investigations. Longitudinal analyses were performed to examine whether VAI could predict T2DM and cardiovascular events. The relationships between VAI and predicted T2DM and cardiovascular events among elderly adults were analyzed in sexes separately in quartile-based analyses.ResultThe study population consisted of 39,590 geriatric patients recruited and the mean age was 65.38 ± 5.09 years. Participants with T2DM had significantly higher VAI (P-values < 0.05). Different subgroups based on sex and VAI quartiles were divided. The median length of follow-up was 8.5 years. The highest VAI level was associated with a significantly higher risk of T2DM compared with the lowest VAI in males (multivariate-adjusted HR 1.77; 95% CI 1.25–2.5; P = 0.001) and females (multivariate-adjusted HR 1.56; 95% CI 1.12–2.15; P = 0.008). The highest VAI quartile was associated with a significantly higher risk of cardiovascular events only in the unadjusted models in males (unadjusted HR 1.65; 95% CI 1.3–2.09; P < 0.001) and females (unadjusted HR 1.69; 95% CI 1.3–2.09, P < 0.001). No association was noted between the VAI quartile and the risk of cardiovascular events after multivariate adjustments.ConclusionWe evaluate the association between VAI and new-onset T2DM and cardiovascular events in the Taiwanese geriatric population. Older adults with higher VAI had a higher incidence of new-onset T2DM after adjusting for covariates. Higher VAI was also associated with a higher risk of cardiovascular events; however, there was no significant difference between the sexes after adjusting for covariates. The risk of VAT accumulation increases with age and affects health. Treatments aimed at depleting VAT should be considered to reduce the risk of diseases.Trial registrationRretrospectively registered
Fast and Accurate Bayesian Polygenic Risk Modeling with Variational Inference
Authors: Zabad Shadi , Gravel Simon , Li Yue
Published: May 2022

The recent proliferation of large scale genome-wide association studies (GWASs) has motivated the development of statistical methods for phenotype prediction using single nucleotide polymorphism (SNP) array data. These polygenic risk score (PRS) methods formulate the task of polygenic prediction in terms of a multiple linear regression framework, where the goal is to infer the joint effect sizes of all genetic variants on the trait. Among the subset of PRS methods that operate on GWAS summary statistics, sparse Bayesian methods have shown competitive predictive ability. However, existing Bayesian approaches employ Markov Chain Monte Carlo (MCMC) algorithms for posterior inference, which are computationally inefficient and do not scale favorably with the number of SNPs included in the analysis. Here, we introduce Variational Inference of Polygenic Risk Scores (VIPRS), a Bayesian summary statistics-based PRS method that utilizes Variational Inference (VI) techniques to efficiently approximate the posterior distribution for the effect sizes. Our experiments with genome-wide simulations and real phenotypes from the UK Biobank (UKB) dataset demonstrated that variational approximations to the posterior are competitively accurate and highly efficient. When compared to state-of-the-art PRS methods, VIPRS consistently achieves the best or second best predictive accuracy in our analyses of 18 simulation configurations as well as 12 real phenotypes measured among the UKB participants of ``White British'' background. This performance advantage was higher among individuals from other ethnic groups, with an increase in R-squared of up to 1.7-fold among participants of Nigerian ancestry for Low-Density Lipoprotein (LDL) cholesterol. Furthermore, given its computational efficiency, we applied VIPRS to a dataset of up to 10 million genetic markers, an order of magnitude greater than the standard HapMap3 subset used to train existing PRS methods. Modeling this expanded set of variants conferred modest improvements in prediction accuracy for a number of highly polygenic traits, such as standing height.
Genetic mapping, transcriptomic sequencing and metabolic profiling indicated a glutathione S-transferase is responsible for the red-spot-petals in Gossypium arboreum
Authors: Zhang Sujun , Chen Jie , Jiang Tao , Cai Xiao , Wang Haitao , Liu Cunjing , Tang Liyuan , Li Xinghe , Zhang Xiangyun , Zhang Jianhong
Published: May 2022

Colored petal spots are correlated with insect pollination efficiency in Gossypium species. However, molecular mechanisms concerning the formation of red spots on Gossypium arboreum flowers remain elusive. In the current study, the Shixiya1-R (SxyR, with red spots) × Shixiya1-W (SxyW, without red spots) segregating population was utilized to determine that the red-spot-petal phenotype was levered by a single dominant locus. This phenotype was expectedly related to the anthocyanin metabolites, wherein the cyanidin and delphinidin derivatives constituted the major partition. Subsequently, this dominant locus was narrowed to a 3.27 Mb range on chromosome 7 by genomic resequencing from the two parents and the two segregated progeny bulks that have spotted petals or not. Furthermore, differential expressed genes generated from the two bulks at either of three sequential flower developmental stages that spanning the spot formation were intersected with the annotated ones that allocated to the 3.27 Mb interval, which returned eight genes. A glutathione S-transferase-coding gene (Gar07G08900) out of the eight was the only one that exhibited simultaneously differential expression among all three developmental stages, and it was therefore considered to be the probable candidate. Finally, functional validation upon this candidate was achieved by the appearance of scattered petal spots with inhibited expression of Gar07G08900. In conclusion, the current report identified a key gene for the red spotted petal in G. arboretum under the scope of multi-omics approaches, such efforts and embedded molecular resources would benefit future applications underlying the flower color trait in cotton.
Identification of cuproptosis-related subtypes, construction of a prognostic model, and characterization of the tumor immune microenvironment in gastric cancer
Authors: Xin Dao , Man Yuxin , Yang Yalan , Wang Feng
Published: May 2022

Background: Gastric cancer represents a significant global public health burden worldwide. Although treatment strategies are continuously improving, the overall prognosis remains poor. Cuproptosis is a newly discovered form of cell death, and the relationship between cuproptosis in tumor immune microenvironment (TIME) and prognosis in STAD has hitherto not been reported.Methods: Stomach adenocarcinoma (STAD) data were downloaded from TCGA and GEO databases. Bioinformatics analysis was performed to construct a cuproptosis-related risk model and identify cancer subtypes. The association between TIME and risk score was comprehensively explored.Results: STAD samples were stratified into three subtypes according to prognostic cuproptosis gene expression. A cuproptosis risk model was constructed and validated based on the expression of 5 genes (RPL39L, PEG10, SYNPO2, MMP11, and KRT17). The model was significantly associated with the prognosis of STAD patients and TIME, including immune cell infiltration, microsatellite instability (MSI) status, tumor mutational burden (TMB) score, immune checkpoint, and human leukocyte antigen (HLA) gene expression. A prognostic nomogram based on the cuproptosis risk score was additionally constructed.Conclusion: We identified a practical prognostic model based on cuproptosis-related genes in STAD and comprehensively established the relationship between cuproptosis and tumor immunity. Further research is warranted on the predictive value of the cuproptosis risk score during immunotherapy in gastric cancer patients in clinical practice and the molecular mechanisms by which cuproptosis influences the TIME.
Understanding 2D MoSe2 grown by CVD
Authors: Fernandes João , Grzonka Justyna , Rodrigues João , Santos João , Bondarchuk Oleksandr , Ferreira Paulo , Alpuim Pedro , Capasso Andrea
Published: May 2022

Extended research on 2D transition metal dichalcogenides (TMDC) revealed viable routes to apply these materials in the semiconductor and (opto)electronic industry. However, fully reproducible methods for the wafer-scale production of crystalline and uniform 2D TMDCs have yet to be established. In this work, atomically thin MoSe2 films were grown on a Si/SiO2 substrate by a standard atmospheric-pressure chemical vapor deposition (CVD) using Se and MoO3 powder precursors. The samples were transferred from the original substrate by using water-soluble polymers as supporting materials, which allowed a clean and efficient transfer process. Extensive characterization was performed via Raman and photoluminescence spectroscopy, atomic force microscopy, transmission electron microscopy and X-ray photoelectron spectroscopy. The CVD growth led to cm-sized, few-layer polycrystalline MoSe2 films made of sub-µm crystalline grains, which are randomly orientated grains and different in lateral size, forming overall fragmented structures. The grains present varying thickness, from bilayer (weakly photoluminescent) to multilayer. Additionally, the different multilayer stacking orientations found on the grown samples give rise to different material phases, as confirmed by TEM. These features need to be taken into consideration for the fabrication of MoSe2-based devices.
FAT4 Overexpression in Peripheral Blood Mononuclear Cells and Tumor Tissues is Associated With a Favorable Prognosis and Promotes Immune Cell Infiltration in Hepatocellular Carcinoma
Authors: Li Jing , Huang Qi , Lv Minling , Zhang Renjie , Ma MengQing , Hu Rui , Zhong Xin , Sun Xinfeng , Feng Wenxing , Han Zhiyi , Ma Wenfeng , Zhang Wei , Zhou Xiaozhou
Published: May 2022

Purpose: To identify prognostically relevant genes in hepatocellular carcinoma, and to investigate whether gene expression in peripheral blood mononuclear cells (PBMCs) and hepatocellular carcinoma tissues can be used as a diagnostic and prognostic marker. Methods: Using RNA-sequencing, gene expression was examined in PBMCs from patients with advanced hepatocellular carcinoma who survived or died. The expression of the top 10 genes in the survival group was validated.Results: The Gene Expression Omnibus and The Cancer Genome Atlas databases were used to analyze FAT atypical cadherin 4 (FAT4) transcript levels in PBMCs and in hepatocellular carcinoma and normal tissues. FAT4 expression was lower in hepatocellular carcinoma than in normal PBMCs and tissues. Kaplan–Meier analysis suggested that downregulated FAT4 was associated with a relatively poor prognosis. The correlation between FAT4 expression and immune cell infiltration was also explored using Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis 2, and the Tumor and Immune System Interaction Database. FAT4 overexpression was positively correlated with immune cell infiltration, several immune cell markers, and immune checkpoint expression. MicroRNAs regulating FAT4 expression were identified using correlation, expression, and survival analyses. Hsa-miR-93-5p was the most likely upstream microRNA of FAT4 in hepatocellular carcinoma.Conclusion: FAT4 is highly expressed in PBMCs and hepatocellular carcinoma tissues, indicating a favorable prognosis and immune cell infiltration in hepatocellular carcinoma, and revealing the potential role of miRNA-93-5p-mediated downregulation of FAT4 in hepatocellular carcinoma immunology. Our findings provide a new direction for the development of novel immunotherapy targets for hepatocellular carcinoma.
High body temperature increases microbiota-dependent host resistance to influenza A virus and SARS-CoV-2 infection
Authors: Ichinohe Takeshi , Nagai Minami , Moriyama Miyu , Ishii Chiharu , Mori Hirotake , Watanabe Hikaru , Nitta Yuuka , Arimitsu Noriko , Nishimoto Moe , Nakahara Taku , Yamada Takuji , Ishikawa Dai , Ishikawa Takamasa , Hirayama Akiyoshi , Kimura Ikuo , Nagahara Akihito , Naito Toshio , Fukuda Shinji
Published: May 2022

While a common symptom of influenza and coronavirus disease 2019 (COVID-19) is fever, its physiological role on host resistance to viral infection remains less clear. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C increase host resistance to viral pathogens including influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High heat-exposed mice increase basal body temperature over 38 °C to enable more bile acids production in a gut microbiota-dependent manner. The microbiota-derived deoxycholic acid (DCA) and its plasma membrane-bound receptor Takeda G-protein-coupled receptor 5 (TGR5) signaling increase host resistance to influenza virus infection by suppressing virus replication and neutrophil-dependent tissue damage. Furthermore, the DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamster from lethal SARS-CoV-2 infection. Moreover, we demonstrate that certain bile acids are reduced in the plasma of COVID-19 patients who developed moderate I/II disease compared with minor illness group. These findings uncover an unexpected mechanism by which virus-induced high fever increases host resistance to influenza virus and SARS-CoV-2 in a microbiota-dependent manner.
Predicting Probabilistic Causes of Colorectal and Gastric Cancers using Bayesian Networks
Authors: Zarei Masoud , Naghibzadeh-Tahami Ahmad , Haghdoost Ali Akbar , Karamoozian Ali
Published: May 2022

Introduction: Being aware of the relationships between risk and protective factors could be helpful to control and prevent diseases. The disease system analysis will be more complex with increasing risk and protective factors. Therefore, in this article, we use Bayesian Networks (BNs) to investigate the relationship between variables and predict the probabilistic causes of colorectal and gastric cancers.Methods: In this study, structure learning algorithms were score-based (hill-climbing) and hypothetical. Parameter learning was estimated by Bayesian method. Network scores (AIC, BIC and BDe), cross-validation methods, and Bayes factor were used to compare both structure learning algorithms and indicate the optimal structure. Data were analyzed by bnlearn R package (ver. 3.0.4). Results: The variables age, gender, smoking, hookah, alcohol, opium, diet, and family history were involved in colorectal and gastric cancers. In both Hill-Climbing and hypothetical algorithms, the odds of developing colorectal and gastric cancers in opium users were (OR = 4.31, OR = 4.35) and (OR = 5.85, OR = 6.06), respectively. Comparing the hypothetical algorithm with network scores and cross-validation showed the hypothetical algorithm was appropriate for colorectal and gastric cancer data. Conclusion: BNs are probabilistic graphical models that demonstrate the cause-and-effect relationship between variables as graphical networks. This method could be beneficial and effective in the fields of biology, medicine, and epidemiology for predicting uncertainty and supporting expert opinions.