bluuebunny/crossref_metadata_2025 huggingface dataset:
Decision-Making for HIV AIDS Prevention: Altruism and the Moral Norm
Authors: Campbell Gordon Evans , Johnson Lester W
Published: January 2021

Background; the purpose of this enquiry was to understand how gay men form and maintain their attitudes towards HIV transmission preventative behaviors. The cost of HIV/AIDS to society is very high and increasing. The pressing need is to increase the rate of behavioral adherence to methods intended to prevent the transmission of the HIV virus to gay men, the most at-risk population. Current knowledge about how to increase/maintain adherence comes from research primarily focused on understanding current behavior. The purpose of this enquiry was to understand more about how gay men initially form and then maintain their attitudes towards preventative behaviors.Methods; Using the Narrative Inquiry method, we recruited sixteen gay men from the Melbourne gay milieu, who narrated their autobiographical life histories. (The term narrated is consistent with the Narrative Inquiry method.). Each narrator’s autobiographical life history was reviewed as one whole, and themes within each were identified. One of the researchers is a gay man who had been immersed in the narrators’ milieu since 1985, closely involved with HIV/AIDS as an experiential phenomenon. He was therefore able to understand each life story as personal experience and embrace it intellectually.Results; Once the narrators acquired knowledge of preventative behavior they consistently adhered to that behavior. They adhered because of fear of HIV infection and because they held a moral norm that obligated them to behave altruistically to achieve values important to them; to protect not only themselves, but also their sex partners, loved ones, and their positive self-evaluation. They saw their HIV negative status, and their adherence, as both pre-requisites and enablers for achieving their goals in life. They took a long-term view of life and planned accordingly. Their autobiographies were a narrative of their life trajectory their Quest for the Ideal Gay Life, in whatever terms they imagined it. Conclusions; Dick and Basu’s Framework for Customer Loyalty, a commercial marketing communications theoretical framework, explains development and maintenance of these men’s loyalty (their consistent adherence). This understanding, within a marketing communications framework, will inform development of social marketing communications aiming to increase adherence to behaviors that prevent HIV transmission.
A potent and protective human neutralizing antibody targeting a key vulnerable site of Epstein-Barr Virus
Authors: Zhu Qian-Ying , Shan Sisi , Yu Jinfang , Peng Si-Ying , Sun Cong , Zuo Yanan , Yan Shu-Mei , Zhang Xiao , Yang Ziqing , Zhong Lan-Yi , Shi Xuangling , Cao Su-Mei , Wang Xinquan , Zeng Mu-Sheng , Zhang Linqi
Published: January 2021

Epstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. Here, we isolated EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralized EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provided strong protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis revealed that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identified a potent neutralizing antibody as a promising candidate for prophylactic and therapeutic interventions against EBV infection. The key vulnerable site also provides insights into the EBV vaccines design.
Investigating the Mechanism of Guizhi Fuling Formula in the Treatment of Primary Dysmenorrhea based on Network Pharmacology and Molecular Docking
Authors: Sun Lu , Wang Zining , Li Jian , Xu Li , Xue Xiaoou
Published: January 2021

Background: Primary dysmenorrhea(PD)is the most common gynecologic disorder.Despite the prevalence is high, it is often underdiagnosed,undertreated and normalized even by patients themselves. Guizhi Fuling Formula (GFF) is experientially used for the treatment of PD in a long time. Therefore, the efficiency and potential mechanism are waiting to identify.Methods: We adopted network pharmacology integrated molecular docking strategy in this study.Based on published literatures, the relative compounds of GFF were selected preliminarily. Secondly, the putative targets of PD were obtained by wide-searching DisGeNET, OMIM, Drugbank and GeneCards databases.With protein-protein interaction(PPI) analysis, GO and KEGG pathway enrichment analysis and molecular docking ,we systematically evaluated the relationship of herb ingredients and disease targets.Results: The results showed that 30 ingredients of GFF and 43 hub targets made a difference.Under the further analysis,8 targets(EGFR,AKT1,PTGS2,TNF,ESR1,AHR,CTNNB1,CXCL8) were recognized as key therapeutic targets with excellent binding. The enrichment analyses indicated that the GFF had the potential to influence varieties of biological pathways, especially the pathways in cancer and steroid hormone biosynthesis, which play an important part in the pathogenesis of primary dysmenorrhea.Conclusion: GFF influenced primary dysmenorrhea through the synergistic effect of multiple components, multiple targets, and multiple pathways.This study predictedthe potential mechanism, hope that could made contribution for clinical application and scientific research.
Mass Transfer and Flow Characterization of Novel Algae Based Nutrient Removal System
Authors: Heyland Andreas , Chau Jeremy , Chai Kevin , Eaton Andrew , Nolan Kathleen , Roszell Jordan , Ahmed Wael H.
Published: January 2021

Background: Recirculating aquaculture systems (RAS) are an essential component of sustainable inland seafood production. Still, nutrient removal from these systems can result in substantial environmental problems, or present a major cost factor with few added value options. In this study, an innovative and energy-efficient algae based nutrient removal system (NRS) was developed that has the potential to generate revenue through algal commercialization. We optimized mass transfer in our NRS design using novel aeration and mixing technology, using air lift pumps and developed an original membrane cartridge for the continuous operation of nutrient removal and algae production. Specifically, we designed, manufactured and tested a 60-liter NRS prototype. Based on specific airlift mixing conditions as well as concentration gradients, we assessed NRS nutrient removal capacity. We then examined the effects of different internal bioreactor geometries and radial orientations on the mixing efficiency. Results: Using the start-up dynamic method, the overall mass transfer coefficient was found to be in the range of 0.00164-0.0074s-1, depending on flow parameters and we confirmed a scaling relationship of mass transfer across concentration gradients. We found the optimal Reynolds number to be 500 for optimal mass transfer, as higher higher Reynolds numbers resulted in a relatively reduced increase of mass transfer. This relationship between mass transfer and Reynolds number is critical to assess scalability of our system. Our results demonstrate an even distribution of dissolved oxygen levels across the reactor core, demonstrating adequate mixing by the airlift pump, a critical consideration for optimal algal growth. Distribution of dissolved gases in the reactor was further assessed using flow visualization in order to relate the bubble distribution to the mass transfer capabilities of the reactor. Conclusions: Manipulation of the concentration gradient across the membrane demonstrates a more prominent role of airlift mixing at higher concentration gradients. Specifically, the mass transfer rate increased 3-fold when the concentration gradient was increased 2.5-fold. Our findings provide support for scalibilty of the design and support the use of this novel NRS for nutrient removal in aquaculture and potentially other applications.
Coordinately Express Hemicellulolytic Enzymes in Kluyveromycesmarxianus to Improve the Saccharification and Ethanol Production From Corncobs
Authors: Lan Qing , Duan Yitong , Wu Pingping , Li Xueyin , Yu Yao , Shi Bo , Zhou Jungang , Lu Hong
Published: January 2021

Background:Hemicelluloses act as one factor contributing to the recalcitrance of lignocelluloses that prevent cellulases to degrade the cellulose efficiently even in low quantities, and supplement of hemicellulases can enhance performance of commercial cellulases in the enzymatic hydrolyses of lignocellulose. K. marxianu is an attractive yeast for cellulosic ethanol fermentation, since it has remarkable thermotolerance, high growth rate, and broad substrate spectrum etc, as well as a promising host for heterologous protein production. In this study, we attempted to coordinately express multiple hemicellulases in Kluyveromyces marxianus through a 2A-mediated ribosomes skipping to self-cleave polyproteins, and investigated their capabilities for saccharification and ethanol production from corncobs.ResultsTwo polycistronic genes IMPX and IMPαX were constructed to test the self-cleavage efficiency of P2A sequence from Foot and Mouth Disease virus (FMDV) in K. marxianus. The IMPX gene consisted of a β-mannanase gene M330 (without the stop codon), a P2A sequence and a β-xylanase gene Xyn-CDBFV in turn, while in the IMPαX gene there was an additional α-factor signal sequence fused at the N-terminus of Xyn-CDBFV. The extracellular β-mannanase activities of IMPX and IMPαX strains were 21.34 and 15.50 U/mL repectively. By contrast, the IMPαX strain secreted 136.17 U/mL β-xylanase, which was much higher than that of IMPX strain, 42.07 U/mL. Based on these, two recombinant strains, the IXαR and IMPαXPαR, were constructed to coordinately and secretorily express the β-D-xylosidase RuXyn1 and Xyn-CDBFV, or three hemicellulolytic enzymes including M330, Xyn-CDBFV and RuXyn1. The IMPαX strain produced 1664.2 and 0.90 U/mL of extracellular β-xylanase and β-xylosidase, while the IMPαXPαR strain secreted 159.8, 2210.5, and 1.25 U/ml of β-mannanase, β-xylanase, and β-xylosidase in fed-batch fermentations respectively. Hemicellulolytic enzymes of these two strains enhanced the releases of both glucose and xylose from diluted acid pretreated corncobs when acted synergistically with commercial cellulases. In hybrid saccharification and fermentation (HSF) of pretreated corncobs, hemicellulases of the IMPαXPαR strain increased about 34.2% and 11.1% of ethanol productions at 144 and 216 h respectively .ConclusionsThe FMDV P2A sequence showed high efficiency in self-cleavage of polyproteins in K. marxianus, and could be used for secretory expression of multiple enzymes in present of their own signal sequences. The IMPαXPαR strain that coexpressed three hemicellulolytic enzymes could be used as a consolidated bioprocessing (CBP) strain for ethanol production from lignocelluloses.
Expression Patterns and Prognostic Value of RUNX Genes in Kidney Cancer
Authors: Gao Ke , Zhang Fang , Chen Ke , Li Wei , Guan Yi-Bing , Xu Meng-Lu , Chong Tie , Dai Zhi-Ming
Published: January 2021

Kidney cancer is the third most common malignancy of the urinary system, of which, kidney renal clear cell carcinoma (KIRC) accounts for the vast majority. Runt-related transcription factors (RUNX) are involved in multiple cellular functions. However, the diverse expression patterns and prognostic values of RUNX genes in kidney cancer remained to be elucidated. In our study, we mined the DNA methylation, transcriptional and survival data of RUNX genes in patients with different kinds of kidney cancer through Oncomine, Gene Expression Profiling Interactive Analysis, UALCAN, Kaplan-Meier Plotter, cBioPortal and LinkedOmics. We found that RUNX1 and RUNX3 were upregulated in KIRC tissues compared with those in normal tissues. The survival analysis results indicated a high transcription level of RUNX1 was associated with poor overall survival (OS) in KIRC patients. Furthermore, KIRC tumor tissues had significantly lower levels of RUNX1 promoter methylation than that in paracancerous tissues, with decreased DNA methylation of RUNX1 notably associated with poor OS in KIRC. In conclusion, our results revealed that RUNX1 may be a potential therapeutic target for treating KIRC, and RUNX1 promoter methylation level shows promise as a novel diagnostic and prognostic biomarker, which laid a foundation for further study.
Brain natriuretic peptide (BNP) and cardiac troponin I(cTnI) for prediction of the prognosis in cancer patients with sepsis
Authors: Yang Yong , Wang Hongzhi , Leng JiaHua , Tian Xiuyun , Hao Chunyi
Published: January 2021

Background

This study aimed to study the value of brain natriuretic peptide (BNP) and cardiac troponin I(cTnI) for predicting the prognosis in cancer patients with sepsis.
Methods

A cohort of 233 cancer patients with sepsis admitted to our ICU from January 2017 to October 2020 was included in this retrospective study. BNP and cTnI on the first day (d1) and the third day(d3) after entering ICU, blood lactate (Lac), procalcitonin (PCT), Leucocyte, Sequential Organ failure assessment (SOFA) scores, the incidence of septic shock, acute kidney injury(AKI), acute respiratory failure (ARF) requiring mechanical ventilation(MV) and sepsis-induced myocardial dysfunction(SIMD) within 24 hours of entering ICU, fluid balance in 24hr and 72hr of entering ICU, time of MV, length of stay in ICU ,emergency surgery were collected. According to the 28-day mortality, these patients were divided into the survival group (190 cases) and the death group (43 cases). All the above variables were compared.
Results

The multiple COX regression analysis of these variables indicated that BNP on d1 and d3, SOFA scores ,72hr fluid balance were independent predictors of the mortality in these patients (P < 0.05); The area under the ROC curve was 0.91 ± 0.01(P < 0.05) for BNP on d3. BNP on d3 at 681.5 pg/mL predicted the mortality with a sensitivity of 91.5% and a specificity of 88.7%. All patients were divided into two groups (BNP on d3 < 681.5 pg/ml or > 681.5 pg/ml), Kaplan-Meier analysis performed on the two groups showed a significant difference in the survival curve (P < 0.05) .There were also significant differences on the comorbidities including shock, AKI, ARF in both groups (P < 0.05). 126 out of 233 patients underwent random bedside echocardiography, and a total of 42 cases developed SIMD with an incidence rate of 33.3% (30.6% in the survival group and 40.9% in the death group). There was no significant difference in the incidence of SIMD between the survival group and the death group (P = 0.23). There was a significant difference between the non-SIMD and the SIMD group for BNP on d1 and d3(P < 0.05).
Conclusions

BNP was a great predictor for the prognosis of cancer patients with sepsis, while cTnI was not.
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

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

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 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

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+ 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

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

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

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

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

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

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

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.
Intensive care unit to unit capacity transfers are associated with increased mortality. An observational cohort study on patient transfers in the Swedish Intensive Care Register
Authors: Parenmark Fredric , Walther Sten M
Published: January 2021

Background
Transfers from one intensive care unit (ICU) to another ICU are associated with increased length of intensive care and hospital stay. We show that non-clinical transfers due to resource constraints in the transferring ICU (capacity transfers) are associated with increased 30- and 180-day mortality compared to repatriations. Inter-hospital ICU Transfers are carried out for three main reasons: clinical transfers, capacity transfers and repatriations. We hypothesised that different ICU transfers differ in risk-adjusted mortality rate with repatriations having the least risk.
Methods
Observational cohort study of adult patients transferred between Swedish ICUs during 3 years (2016–2018) with follow up ending September 2019. Primary and secondary end-points were survival to 30 days and 180 days after discharge from the first ICU. Data from 75 ICUs in the Swedish Intensive Care Register, a nationwide intensive care register, was used for analysis (89 % of all Swedish ICUs). Covering local community hospitals, district general hospitals and tertiary care hospitals. We included adult patients (16 yrs. or older) admitted to ICU and subsequently discharged by transfer to another ICU. Only the first admission was used. Exposure was discharge to any other ICU (ICU to ICU transfer), whether in the same or in another hospital. Transfers were grouped into three predefined categories: clinical transfer, capacity transfer, and repatriation.
Results
We identified 15,588 transfers among 112,860 admissions (14.8 %) and analysed 11,176 after excluding 4,112 repeat transfer of the same individual and 300 with missing risk adjustment. The majority were clinical transfers (62.7 %), followed by repatriations (21.5 %) and capacity transfers (15.8 %). Unadjusted 30-day mortality was 25.0% among capacity transfers compared to 14.5% and 16.2% for clinical transfers and repatriations respectively. Adjusted odds ratio (OR) for 30-day mortality were 1.25 (95% CI: 1.06–1.49 P = .01) for capacity transfers and 1.17 (95% CI: 1.02–1.36 P = .03) for clinical transfers using repatriation as reference. The differences remained 180 days post discharge.
Conclusions
There was a large proportion of ICU to ICU transfers and an increased odds of dying for those transferred due to other reasons than repatriation.
Preprint Servers’ Policies, Submission Requirements, and Transparency in Reporting and Research Integrity Recommendations
Authors: Malicki Mario , Jerončić Ana , Bouter Lex , Riet Gerben ter , Ioannidis John P.A. , Goodman Steven M. , Aalbersberg IJsbrand Jan
Published: January 2021

In light of the recent increase in the number of preprints and preprints servers, as well as calls for transparent reporting of research, we conducted a cross-sectional analysis of 57 preprint servers’ websites for information on their policies, submission requirements, and transparency in reporting and research integrity recommendations. All servers specified their scope, and a large majority mentioned they apply moderation or screening procedures (n=47, 82%). Out of 18 analysed topics on transparency in reporting and research integrity, the servers addressed a median of 1 (IQR 1 to 3), most commonly data sharing (n=22, 39%), plagiarism (n=15, 26%) and the use of ORCID iD (n=14, 25%). Preprint servers could do more to raise awareness and encourage or require transparent reporting of research and adherence to research integrity standards. In doing so they may improve the quality and trust in the scholarly information exchange.
Late time transition in the evolution of the Universe
Authors: Aydiner Ekrem , Oz Isil Basaran , Dereli Tekin , Sarisaman Mustafa
Published: January 2021

The late time crossover from a power-law to an exponential expansion of the Universe evolution is the major problem in today’s physical cosmology. Unless this critical transition problem is solved, it is not possible to reach a holistic theory of cosmology. In this study, we propose a simple model in the FLRW framework, where dark matter and dark energy interact through a potential. We analytically solve this model and obtain scale factor a(t) from the presented model. Mainly, employing numerical solutions we show that the scale parameter has a hybrid form which includes power and exponential terms. The numerical results clearly show that there is a time crossover tc in the scale factor a(t) curve, which indicates the transition from the power-law to the exponential expansion of the Universe. We ﬁt these unscaled curves and obtain that scale factor behaves as a(t) ∝ t2/3 below t ≤ tc, and as a(t) ∝ exp(H0t) with H0 = 0.4 and H0 = 0.3 for the relatively weak and strong interactions above t > tc, respectively. It is the ﬁrst time that we explicitly obtain a hybrid scale factor incorporating the power and exponential terms as a(t) ∝ t2/3eH0t . We conclude that the presented model can solve the late time transition problem of the Universe based on dark matter and dark energy interaction. Additionally, we numerically obtain other kinematic parameters depending upon the scale factor. We discuss the limit behaviors of all relevant cosmological parameters. Our results are completely in good agreement with observational data. Finally, we state that this work makes essential steps towards solving a critical outstanding problem of the cosmology, and has a potential to creates a paradigm for future studies in this ﬁeld.
Phase 2b open label randomized controlled trial to evaluate the efficacy, safety and tolerability of N-acetylcysteine in reducing adverse drug reactions among adults treated for multidrug-resistant tuberculosis in Tanzania. (Trial Acronym NAC Trial).
Authors: Mpagama Stellah
Published: January 2021

Background: Adverse drug reactions (ADRs) frequently occur in patients using second-line anti-tuberculosis medicine for treatment of multidrug resistant tuberculosis (MDR-TB). ADRs contribute to treatment interruptions which can compromise treatment response and risk acquired drug resistance to critical newer drugs such as bedaquiline, while severe ADRs carry considerable morbidity and mortality. N-acetylcysteine (NAC) has shown promise in reducing ADRs for medications related to TB in case series or randomized controlled trials in other medical conditions. We therefore designed a pilot clinical trial to study the protective effect of NAC among people treated for MDR-TB with second-line anti-TB medications. Methods: This is a phase 2b randomized open label clinical trial with 3 treatment arms including a control arm, an interventional arm of NAC 900mg daily, and an interventional arm of NAC 900mg twice-daily administered during the intensive phase of MDR-TB treatment. Patients initiating MDR-TB treatment will be enrolled at Kibong’oto National Center of Excellence for MDR-TB in the Kilimanjaro region of Tanzania. The minimum anticipated sample size is 66; with 22 participants in each arm. ADR monitoring will be performed at baseline and regular follow-up over 24 weeks including blood and urine specimen collection for hepatic and renal function and electrolyte abnormalities, electrocardiogram and hearing function by pure tone audiometry. Sputum will be collected at baseline and monthly thereafter and cultured for mycobacteria as well as assayed for other molecular targets of Mycobacterium tuberculosis. Adverse drug events will be analyzed over time using mixed effect models. Mean differences between arms in change of the ADRs from baseline (with 95% confidence intervals) will be derived from the fitted model.Discussion: Given that NAC promotes synthesis of glutathione, an intracellular antioxidant that combats the impact of oxidative stress, it may protect against medication induced oxidative damage in organs such as liver, pancreas, kidney and cells of the immune system. This randomized controlled trial will determine if NAC leads to fewer ADRs, and if this protection is dose dependent. Fewer ADRs among patients treated with MDR-TB may significantly improve treatment outcomes for multidrug regimens that necessitate prolonged treatment durations.Trial registration: PACTR202007736854169