bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safe Threshold of Capillary Blood Glucose for Predicting Early Future Neonatal Hypoglycaemia in Babies Born to Mothers With Gestational Diabetes Mellitus, an Observational Study
Authors: Park Esther H.G. , O’Brien Frances , Seabrook Fiona , Hirst Jane Elizabeth 
Published: January 2021

Abstract
Background: There is increasing pressure to get women and babies home rapidly after birth. Babies born to mothers with gestational diabetes mellitus (GDM) currently get 24-hour inpatient monitoring. We investigated whether a low-risk group of babies born to mothers with GDM could be defined for shorter inpatient hypoglycaemia monitoring. Methods: Observational study conducted in a tertiary maternity hospital in 2018. Singleton, term infants born to women with GDM and no other risk factors for hypoglycaemia, were included. Capillary blood glucose (BG) testing and clinical observations for signs of hypoglycaemia during the first 24-hours after birth. BG was checked in all babies before the second feed. Subsequent testing occurred if the first result was <2.0mmol/L, or clinical suspicion developed for hypoglycaemia. Neonatal hypoglycaemia, defined as either capillary or venous glucose ≤2.0mmol/L and/or clinical signs of neonatal hypoglycaemia requiring oral or intravenous dextrose (lethargy, abnormal feeding behaviour or seizures). Results: Fifteen of 106 babies developed hypoglycaemia within the first 24-hours. Maternal and newborn characteristics were not predictive. All babies with hypoglycaemia had an initial capillary BG ≤2.6mmol/L (Area under the ROC curve (AUC) 0.96, 95% Confidence Interval (CI) 0.91-1.0). This result was validated on a further 65 babies, of whom 10 developed hypoglycaemia, in the first 24-hours of life.Conclusions for practice: Using the 2.6mmol/L threshold, extended monitoring as an inpatient could have been avoided for 60% of newborns in this study. Whilst prospective validation is needed, this approach could help tailor postnatal care plans for babies born to mothers with GDM.
Anti-Tumor and Anti-Invasive Effects of ONC201 on Ovarian Cancer Cells and a Transgenic Mouse Model of Serous Ovarian Cancer
Authors: Fan Yali , Wang Jiandong , Fang Ziwei , Pierce Stuart R , West Lindsay , Staley Allison , Tucker Katherine , Yin Yajie , Sun Wenchuan , Kong Weimin , Prabhu Varun , Allen Joshua E , Zhou Chunxiao , Bae-Jump Victoria L 
Published: January 2021

Abstract
Background: ONC201 is a promising first-in-class small molecule that has been reported to have anti-neoplastic activity in various types of cancer through activation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as well as activation of mitochondrial caseinolytic protease P (ClpP).Methods: Our objective was to evaluate the effect of the ONC201 on (1) proliferation, cellular stress, apoptosis and invasion in human serous ovarian cancer (OC) cell lines, and (2) inhibition of tumor growth in a genetically engineered mouse model of high grade serous OC (K18-gT121+/-;p53fl/fl;Brca1fl/fl; KpB) under obese (high fat diet) and lean (low fat diet) conditions. Results: ONC201 significantly suppressed cell proliferation, induced arrest in G1 phase, and increased cellular stress and apoptosis, accompanied by dual inhibition of the AKT/mTOR/S6 and MAPK pathways in OC cells. ONC201 also resulted in inhibition of adhesion and invasion via epithelial–mesenchymal transition and reduction of VEGF expression. Pre-treatment with the anti-oxidant, N-acetylcysteine (NAC), reversed the ONC201-induced oxidative stress response, and prevented ONC201-reduced VEGF and cell invasion by regulating epithelial–mesenchymal transition protein expression. Knockdown of ClpP in ovarian cancer cells reduced ONC201 mediated the anti-tumor activity and cellular stress. Diet-induced obesity accelerated ovarian tumor growth in the KpB mouse model. ONC201 significantly suppressed tumor growth, and decreased serum VEGF production in obese and lean mice, leading to a decrease in tumoral expression of Ki-67, VEGF and phosphorylation of p42/44 and S6 and an increase in ClpP and DRD5, as assessed by immunohistochemistry. Additionally, ONC201 exhibited greater anti-tumor efficacy in obese (75%) as compared to lean (65%) mice. InterpretationConclusions: These results suggest that ONC206 may be a promising therapeutic agent to be explored in future clinical trials in high grade serous OC.
HMGA1-TRIP13 Axis Promotes Stemness and Epithelial Mesenchymal Transition&nbsp;of Perihilar Cholangiocarcinoma in a Positive Feedback Loop Dependent on C-Myc
Authors: Li Zhipeng , Liu Jialiang , Chen Tianli , Sun Rongqi , Liu Zengli , Qiu Bo , Xu Yunfei , Zhang Zongli 
Published: January 2021

Abstract
Background: Cholangiocarcinoma is a highly malignant cancer with very dismal prognosis. Perihilar cholangiocarcinoma(pCCA) accounts for more than 50% of all cholangiocarcinoma and is well-characterized for its low rate of radical resection. Effects of radiotherapy and chemotherapy of pCCA are very limited. Methods: Here we screened potential biomarkers of pCCA with transcriptome sequencing and evaluated the prognostic significance of HMGA1 in a large cohort pCCA consisting of 106 patients. With bioinformatics and in vitro/vivo experiments, we showed that HMGA1 induced tumor cell stemness and epithelial-mesenchymal-transition(EMT), and thus facilitated proliferation, migration and invasion by promoting TRIP13 transcription. Moreover, TRIP13 was also an unfavorable prognostic biomarker of pCCA, and double high expression of HMGA1/TRIP13 could predict prognosis more sensitively. TRIP13 promoted pCCA progression by suppressing FBXW7 transcription and stabilizing c-Myc. c-Myc in turn induced the transcription and expression of both HMGA1 and TRIP13, indicating that HMGA-TRIP13 axis facilitated pCCA stemness and EMT in a positive feedback pathway. Conclusions: HMGA1 and TRIP13 were unfavorable prognostic biomarkers of pCCA. HMGA1 enhanced pCCA proliferation, migration, invasion, stemness and EMT, by inducing TRIP13 expression, suppressing FBXW7 expression and stabilizing c-Myc. Moreover, c-Myc can induce the transcription of HMGA1 and TRIP13, suggesting that HMGA-TRIP13 axis promoted EMT and stemness in a positive feedback pathway dependent on c-Myc.
Functional and Molecular Characterization of PD1+&nbsp;Tumor-Infiltrating Lymphocytes From Lung Cancer Patients
Authors: Lipp Jesse , Wang Limei , Harrer Nathalie , Mueller Stefan , Berezowska Sabina , Dorn Patrick , Marti Thomas M , Kocher Gregor J , Hegedues Balazs , Souabni Abdallah , Carotta Sebastian , Pearson Mark A , Sommergruber Wolfgang , Schmid Ralph A , Hall Sean RR 
Published: January 2021

Abstract
Background The majority of infiltrating T-cells (TILs) in lung cancer are contained in the memory compartment and overexpress PD1 and have been associated with dysfunction. Antibody-mediated cancer immunotherapy targets inhibitory surface molecules, such as PD1, PD-L1, and CTLA-4, aiming to re-invigorate dysfunctional T cells.Methods Using fluorescence-activated cell sorting (FACS), we purified CD45RO+ memory CD8+ and CD4+ TILs and their patient-matched non-tumor counterparts from treatment-naïve NSCLC patient biopsies to better evaluate the effect of PD1 expression on the functional and molecular profile of tumor-resident T cells. Moreover, we compared the functional, molecular, and clonal composition of TIL preparations after TCR-dependent in vitro expansion with their freshly isolated counterparts in matched patients.Results We show that PD1+CD8+ TILs have elevated expression of the transcriptional regulator ID3 and that the overall cytotoxic potential of CD8 T cells can be improved by knocking down ID3, defining it as a potential regulator of T cell effector function. PD1+CD4+ memory TILs remain functionally intact and despite overexpressing key transcriptional activators known to negatively regulate CD8 function such as TOX and TOX2, display transcriptional patterns consistent with both follicular helper and regulator function and robustly facilitate B cell activation and expansion in response to TCR-dependent stimulation. Furthermore, we show that expanding ex vivo-prepared TILs in vitro in a TCR-dependent manner broadly preserves their functionality with respect to tumor cell killing, expansion and activation of B cells, and TCR repertoire. Although purified PD1+CD8+ TILs generally maintain an exhausted phenotype upon expansion in vitro, transcriptional analysis reveals a downregulation of markers of T cell dysfunction, including the co-inhibitory molecules PD1 and CTLA-4 and the transcription factors ID3, TOX and TOX2, while genes involved in cell cycle and DNA repair are upregulated. We find reduced expression of WNT signaling components to be a hallmark of PD1+CD8+ exhausted T cells in vivo and in vitro and demonstrate that restoring WNT signaling, by pharmacological blockade of GSK3β, can improve effector function. Conclusions These data unveil novel targets for tumor immunotherapy and have promising implications for development of a personalized adoptive TIL-based cell therapy for lung cancer.
Weather Factors Associated with Reduced Risk of Dengue Transmission in an Urbanized Tropical City
Authors: Gui Hao , Gwee Sylvia , Koh Jiayun , Junxiong Pang 
Published: January 2021

Abstract
BackgroundThe association of weather factors on dengue transmission in an urbanized tropical environment remains inconclusive. This study aims to assess the impact of weather factors on dengue incidence in Singapore between 2012 and 2019.MethodsData on weather variables (daily temperature, air quality, rainfall & wind speed) and weekly dengue incidence rates were collected from 1 January 2012 to 25 August 2019. Statistically significant correlated variables identified from cross-correlation analysis using Pearson’s correlation were examined in univariate ARIMA model. A distributed lag non-linear model (DLNM) with Quasi-Poisson model was established to assess any non-linear association between climatic factors and dengue incidence. The Quasi-Poisson model coefficients were evaluated using Quasi Akaike’s Information Criterion (QAIC). To validate the model, the data was split into testing and validation sets, with QAIC, Mean Absolute Error (MAE) & Root Mean Square Error (RMSE) reported. ResultsPollutant Standards Indices (PSI) greater than 100 was associated to lower weekly dengue incidence at a 5-week and a 7-week lag period. High wind speeds at 5-week lag time was also associated with reduced dengue transmission. Mean and minimum temperatures of 28℃ and 25℃ respectively were associated with reduced risk of weekly dengue transmission across all lags effect. Mean temperatures above 28℃ at a 1-week lag and maximum temperatures above 32℃ at an 11-week lag promoted dengue transmission. Rainfall was not correlated with dengue cases in Singapore.Based on split-sample model validation, mean temperature was the best predictor of dengue (MAE: 43.15, RMSE: 51.39). Weather factors had varied influence on both pre-epidemic surge periods and non-epidemic periods, but had a stronger correlation with dengue transmission in non-epidemic periods. ConclusionsPoor air quality and high wind speeds were associated with reduced risk of dengue transmission in an urbanized tropical environment. Only a limited temperature range promotes dengue transmission.
Distinct Sensorimotor Feedforward and Feedback Deficits Vary with Age in Individuals with Autism Spectrum disorder
Authors: Unruh Kathryn E , McKinney Walker S , Fleming Kandace K , Sweeney John A , Mosconi Matthew W 
Published: January 2021

Abstract
Background: Sensorimotor issues are common in autism spectrum disorder (ASD), related to core symptoms, and predictive of worse functional outcomes. Deficits in rapid, feedforward processes executed prior to availability of sensory feedback, and continuous, feedback-guided motor behaviors each have been reported, but the degree to which these deficits are distinct or co-segregate in individuals is not well understood. Methods: To characterize feedforward and feedback control of motor behavior in ASD, we examined saccadic eye movements (feedforward) and sustained precision gripping (feedback) in 109 individuals with ASD and 101 age-matched typically developing (TD) controls (range: 5-28 years). We measured latency and gain of saccades and error, variability, and regularity of precision grip. Linear mixed effects models were conducted to examine whether sensorimotor behavior varied according to diagnostic group, age, handedness, and sex. Results: Individuals with ASD showed reduced accuracy of saccadic eye movements relative to controls, and their dysmetria was more severe at older ages. Individuals with ASD showed increased precision grip force variability relative to controls, especially at younger ages, while increased motor regularity was more pronounced in older individuals with ASD. Feedforward and feedback motor behaviors were strongly inter-related among controls, but not among individuals with ASD. Saccade dysmetria and increased force variability were associated with ASD symptom severity. Limitations: Our age-related findings rely on cross-sectional data. Longitudinal studies of component motor skills and their associations with clinical outcomes are needed to clarify neurodevelopmental mechanisms of core and associated symptoms of ASD. Feedforward behavior was characterized in the oculomotor system using ballistic movements completed too rapidly to be guided by online feedback; however, future studies are needed to examine feedforward and feedback processes across both manual and oculomotor systems. Conclusions: These findings suggest that separate neurodevelopmental mechanisms contribute to feedforward and feedback motor deficits in ASD, and that they are more manifest at different stages in life span development. Our results highlight the needs for more fine-grained approaches to parse separate motor impairments that often are considered as a unitary deficit in ASD, and to characterize variation in motor behaviors across development.
Predictors of Heart and Lung Dose in Left-sided Breast Cancer Treated with VMAT Relative to 3D-CRT：A Retrospective Study
Authors: Kang Zheng , Chen Sijia , Shi Liwan , He Yipeng , Gao Xiang 
Published: January 2021

Abstract
Background

Before radiotherapy for breast cancer patients, the choice of three-dimensional conformal radiation therapy (3D-CRT) and volumetric modulated arc therapy (VMAT) should be made. This study investigates the performance of two structural metrics in aiding the choice of 3D-CRT and VMAT plans in women undergoing left-sided whole breast radiotherapy.
Materials and methods

119 patients previously treated with left-sided breast radiotherapy (61 3D-CRT treatments and 58 VMAT treatments) from a single institution were retrospectively studied. Two structural metrics, which are cardiac intersetion (CI) index and pulmonary intersection (PI) index, were defined and the relationship between these metrics and dose of organs at risk (OARs) were evaluated. Two-tailed Student’s t-test was performed to compare patient characteristics between 3D-CRT and VMAT. Linear regressions were calculated to investigate the association between structural metrics and absorbed dose of heart and left lung, including MHD, V5, V30 of heart, and MLLD, V5, V10, V20, V30, V40 of left lung.
Results

The CI index was strongly correlated with the mean dose of heart (MHD) in 3D-CRT group and VMAT group, the linear regression formulas were MHD = 4826.59 ×CI Index + 310.48 (R = 0.857, F = 163.77, P = 0.000) in 3D-CRT plans and MHD = 1789.29×CI Index + 437.50 (R = 0.45, F = 14.23, P = 0.000) in VMAT plans, the intercept of these formulas was CI index = 4.2% and MHD = 512.33 cGy. The PI index demonstrated a strongly positive correlation with mean dose of left lung (MLLD) in 3D-CRT group and VMAT group as well, the linear regression formulas were MLLD = 2879.54×PI Index + 999.79 (R = 0.697, F = 55.86, P = 0.000) in 3D-CRT plans and MLLD = 1411.79×PI Index + 1091.88 (R = 0.676, F = 47.11, P = 0.000) in VMAT plans, the intercept of these formulas was PI index = 6.3% and MLLD = 1180.46 cGy.
Conclusions

CI index and PI index could serve as a practical tool of choosing either 3D-CRT or VMAT before the plan was generated. We recommend that VMAT plan is preferable when CI index is greater than 4.2% and PI index is greater than 14.6%, while 3D-CRT plan is the first choice in the opposite.
Attitudes and Behaviors Regarding Sun-Protection Practices Among Minority Groups in a Lower Socioeconomic Community
Authors: Nguyen Alexander T , Fergus Jonathan , Engel Tess N , Ashfaq Adeel , Luong James , Dellavalle Robert P , Maverakis Emanual , Sivamani Raja 
Published: January 2021

Abstract
Background: Although skin cancer is less common, minorities present with more advanced stages at diagnosis and have worse outcomes. Literature on this disparity is limited.Objective: To evaluate attitudes influencing sun protective behaviors, skin cancer risk perception, and dermatologist access among an underserved, racially/ethnically diverse community.Methods: A cross-sectional survey of patients at 5 ethnically diverse student-run, free primary care clinics in Sacramento, California.Results: 390 surveys were collected with a response rate: 86.4%. Overall, respondents did not use sunscreen, rarely sunburned, were unsure or perceived themselves at low risk for skin cancer and reported limited access to dermatologists. Compared to Whites, Latinos were likely to believe it was not worth getting sunburned to be tan (OR = 24.43, 95% CI: 9.37 to 63.3, P < 0.0001). Whites were more likely than Asians (OR = 3.69, 95% CI: 1.50 to 9. 11, P = 0.004) and Latinos (OR = 4.83, 95% CI: 1.83 to 12.8, P = 0.001) to perceive access to dermatology care.Limitations: Response bias, sampling bias, generalizabilityConclusions: Ethnic groups differ in knowledge of sun protection and self-perceived skin cancer risk. The Latino community showed discrepancies between sun protection knowledge and practices, serving as an interventional target.
“Sometimes You Reach a Point Where You Feel Burnt Out”, Job Satisfaction and Psychosocial Well Being of COVID-19 Frontline Health Workers: a Qualitative Study in Two Ugandan COVID-19 Treatment Centres.
Authors: Nelson Twinamasiko , Twimukye Adelline , Gwokyalya Anna Maria , Nakityo Innocent , Wasswa Enock , Sserunjogi Emmanuel , Lamorde Mohammed , Mayanja Harriet Kizza , Rwamafa Pius 
Published: January 2021

Abstract
BACKGROUND: COVID-19 has become a major global health challenge, with Uganda reporting over 25,000 cases. Frontline healthcare workers (HCWs) are the most at risk population for mental health disorders yet their well-being is key to combating the pandemic. We explored the psychosocial wellbeing and job satisfaction of COVID-19 Frontline HCWs in Uganda.METHODS: This was a qualitative study done at Entebbe regional Referral hospital (ERRH) and Mulago National Referral hospital (MNRH) in September 2020. Data collection was through 3 Focus Group Discussions (FGDs) with 5 participants for each FGD. 2 FGDs were at MNRH and 1 at ERRH. Participants included; doctors, nurses, laboratory personnels, hygienists and a security personnel. Interviews were audio-recorded, transcribed and analyzed thematically using Nvivo version 12 software.RESULTS: Despite the challenges HCWs faced, they were motivated to work when they saw patients recover and go home safely. Participants felt the Pandemic was unprecedented and as a result no person or government was fully prepared. Big unexpected patient crowds caused limited and/ or inconsistent medical supplies. Additionally, Poor Procurement lines affected sufficiency of medical supplies and equipment such as medical gowns, drugs, PPE, alcohol, beds, and COVID-19 testing kits. There was knowledge gap among the HCWs regarding COVID-19 management. This put the staff in a Panic situation hence practicing “trial and error” treatment. Poor remuneration in terms of low or delayed Salary, lack or delay of risk allowance caused dissatisfaction among staff and were affected mentally given that they were involved in risky work yet their families were suffering economically.CONCLUSION: HCWs were remarkably stressed, exhausted and burnt-out due to the heavy workload and inadequate personal protective Equipment. These findings depict a need of creating a conducive environment for these HCWs. Government and ministry should re-strategize on how well to take care of Covid 19 frontline HCWs to save lives.
Epidemiology, Pathogens Distribution, Antibiotic Susceptibility and the Risk Factors for Mortality of Patients With Central Nervous System Infections: a Retrospective Study From 2012 to 2019 in a Teaching Hospital in China
Authors: Zhang Zheng , Song Yan , Kang Jianbang , Duan Surong , Li Qi , Feng Fuqiang , Duan Jinju 
Published: January 2021

Abstract
Background: Central nervous system (CNS) infections are relatively rare but associated with high mortality worldwide. Empirical antimicrobial therapy is crucial for the prognosis of patients with CNS infections, which should be based on the knowledge of pathogens distribution and antibiotic sensitivities. China is a vast country, and the pathogens distribution varies nationwide. The aim of this study is to investigate the features of pathogens in patients with CNS infections in north China and we tried to evaluate the risk factors for mortality.Methods: We retrospectively analyzed the patients with positive cerebrospinal fluid (CSF) culture in a teaching hospital between January 2012 and December 2019. The following information were collected: demographic characteristics, laboratory data, causative organisms and antimicrobial susceptibility results. Univariate analysis and binary logistic regression analysis were performed to identify the risk factors for mortality.Results: In this eight-year retrospective study, a total of 72 patients were diagnosed with CNS infections and 86 isolates were identified. Among all the microorganisms detected, Gram-positive strains consisted of 59.3%, Gram-negative bacteria of 30.2% and fungi of 10.5%. The predominant Gram-positive isolate was coagulase-negative staphylococci. Acinetobacter baumannii, Escherichia coli and Klebsiella were the common Gram-negative strains. Compared to 2012-2015 years, the proportion of Gram-negative bacteria increased markedly during 2016-2019 years. Vancomycin, teicoplanin and linezolid were still 100% sensitive to Gram-positive bacteria. For the multidrug-resistant Gram-negative bacteria, only tigecycline was the 100% sensitive antibiotics. The mortality of the 72 patients was 30.6%. In the multivariate analysis, age >50 years, combined pulmonary infection and CSF glucose < normal value were associated with poor prognosis. Conclusions: CNS infections cause high mortality worldwide. Although Gram-positive bacteria are still the primary pathogen of CNS infections, Gram-negative bacteria had increased in recent years and should be considered in the choice of empirical antibiotic treatment. Special attention should be given to older patients and those combined pulmonary infection and with low CSF glucose level.