bluuebunny/crossref_metadata_2025 huggingface dataset:
The TNFA -308G>A and IL10 -1082A>G Polymorphisms as Predictive Biomarkers of Chronic HCV Infection
Authors: Santiago Angélica Menezes , Amoras Ednelza da Silva Graça , Queiroz Maria Alice Freitas , Conde Simone Regina Souza da Silva , Cayres-Vallinoto Izaura Maria Vieira , Ishak Ricardo , Vallinoto Antonio C. R.
Published: September 2020

Background: Genetic changes may induce dysregulated cytokine production and affect the progression of the chronic disease caused by the hepacivirus C (HCV) because the balance of pro- and anti-inflammatory cytokines determines the outcome of infection. This study evaluated the TNFA -308G>A and IL10 -1082A>G polymorphisms in the susceptibility and progress of chronic hepatitis CMethods: The study included 101 samples from patients with chronic hepatitis C and 300 samples from healthy donors. Polymorphisms were typed by real-time PCR and were analyzed for associations with histopathological parameters (according to METAVIR classification) and HCV viral load. Results: The polymorphic genotype for the TNFA -308G>A variant was not present in the group of patients with chronic hepatitis C and was associated with protection against HCV infection (p = 0.0477). Patients with the polymorphic genotype of the IL10 -1082A>G polymorphism had higher HCV viral load than wild-type patients (p = 0.0428). Neither polymorphism was associated with different levels of necroinflammatory activity or fibrosis scores. Conclusion: The polymorphic genotype at TNFA -308G>A protected against chronic HCV infection, and the polymorphic genotype at the IL10 -1082A>G variant was associated with viral persistence.
Manufacturing and Banking Canine Adipose-Derived Mesenchymal Stem Cells for Veterinary Clinical Application
Authors: Luo Huina , Li Dongsheng , Chen Zhisheng , Wang Bingyun , Chen Shengfeng
Published: September 2020

BACKGROUND: Mesenchymal stem cells (MSCs) have generated a great amount of interest in recent years as a novel therapeutic application for improving the quality of pet life and helping them free from painful conditions and diseases. It has now become critical to address the challenges related to the safety and efficacy of MSCs expanded in vitro. In this study, we establish a standardized process for manufacture of canine adipose-derived MSCs (AD-MSCs), including tissue sourcing, cell isolation and culture, cryopreservation, thawing and expansion, quality control and testing, and evaluate the safety and efficacy of those cells for clinical applications. RESULTS: After expansion, the viability of AD-MSCs manufactured under our standardized process was above 90 %. Expression of surface markers and differentiation potential was consistent with ISCT standards. Sterility, mycoplasma, and endotoxin tests were consistently negative. No adverse events were noted in two cases treated with intravenously AD-MSCs. CONCLUSION: Herein we demonstrated the establishment of a feasible bioprocess for manufacturing and banking canine AD-MSCs for veterinary clinical use.
Effects of Hyaluronidase on Structural Cells and the Extracellular Matrix of the Skin
Authors: Buhren Bettina Alexandra , Schrumpf Holger , Gorges Katharina , Reiners Oliver , Boelke Edwin , Fischer Jens W , Homey Bernhard , Gerber Peter Arne
Published: September 2020

Hyaluronic acid (hyaluronan; HA) is an essential component of the extracellular matrix (ECM) of the skin. The HA-degrading enzyme hyaluronidase (HYAL) is critically involved in the HA-metabolism. Yet, only little information is available regarding the skin´s HA-HYAL interactions on the molecular and cellular levels.OBJECTIVETo analyze the dose- and time-dependent molecular and cellular effects of HYAL on structural cells and the HA-metabolism in the skin.MATERIALS AND METHODSChip-based, genome-wide expression analyses (Affymetrix® GeneChip PrimeView™ Human Gene Expression Array), quantitative real-time PCR analyses, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (DAB), and in vitro wound healing assays were performed to assess dose-dependent and time-kinetic effects of HA and HYAL (bovine hyaluronidase, Hylase “Dessau”) on normal human dermal fibroblasts (NHDF), primary human keratinocytes in vitro and human skin samples ex vivo.RESULTSGenome-wide expression analyses revealed an upregulation of HA synthases (HAS) up to 1.8-fold change in HA- and HYAL-treated NHDF. HA and HYAL significantly accelerated wound closure in an in vitro model for cutaneous wound healing. HYAL induced HAS1 and HAS2 mRNA gene expression in NHDF. Interestingly, low concentrations of HYAL (0.015 U/ml) resulted in a significantly higher induction of HAS compared to moderate (0.15 and 1.5 U/ml) and high concentrations (15 U/ml) of HYAL. This observation corresponded to increased concentrations of HA measured by ELISA in conditioned supernatants of HYAL-treated NHDF with the highest concentrations observed for 0.015 U/ml of HYAL. Finally, immunohistochemical analysis of human skin samples incubated with HYAL for up to 48 h ex vivo demonstrated that low concentrations of HYAL (0.015 U/ml) led to a pronounced accumulation of HA, whereas high concentrations of HYAL (15 U/ml) reduced dermal HA-levels.CONCLUSIONHYAL is a bioactive enzyme that exerts multiple effects on the HA-metabolism as well as on the structural cells of the skin. Our results indicate that HYAL promotes wound healing and exerts a dose-dependent induction of HA-synthesis in structural cells of the skin. Herein, interestingly the most significant induction of HAS and HA were observed for the lowest concentration of HYAL.
Brucine Inhibits Proliferation of U87 Glioblastoma Cells by Targeting the G-quadruplexes in the c-Myb Promoter
Authors: Liu Qiaochu , Huo Di , Wang Qunhui , Lv Chuanqi , Liu Ziqiang , Gao Haijun , Chen Yong , Zhao Gang
Published: September 2020

Background: The proto-oncogene c-Myb plays an important role in the proliferation of cells and its upregulation affects the development of glioblastomas. G-quadruplexes are secondary structures of DNA or RNA that usually form in the promoter region of oncogenes, including c-Myb, and regulate the expression of these genes. The traditional Chinese medicine brucine is a ligand of G-quadruplexes located in the promoter region of c-Myb. In this study, the U87 cell line was used both in vitro and in vivo to investigate the therapeutic effect and mechanism of action of brucine. Methods: MTT assay and flow cytometry were used to determine the effect of brucine on the cell cycle, viability, and apoptosis of U87 cells. The effects of brucine on transcription and expression of c-Myb were determined through RT-PCR and western blotting. Dual-luciferase reporter assay and electrospray ionization-mass spectrometry were used to investigate whether brucine acts directly and binds G-quadruplexes in the promoter region of c-Myb, respectively. Results: The results showed that brucine suppressed the growth of U87 cells in vitro by arresting the cell cycle and reducing the expression of c-Myb. Through the dual luciferase reporter assay, brucine was found to inhibit the expression of c-Myb by targeting the guanine-rich sequence that forms G-quadruplexes in the c-Myb promoter. Moreover, U87 tumors were suppressed by brucine in a tumor xenograft nude mice model. Conclusion: The findings of the study indicate that brucine is a potentially effective medicine for treatment of glioblastomas.
Intrinsic oxidative phosphorylation limitations underlie cellular bioenergetics in leukemia.
Authors: Nelson Margaret , McLaughlin Kelsey , Hagen James , Coalson Hannah , Schmidt Cameron , Kew Kimberly , McClung Joseph , Neufer P. , Brophy Patricia , Vohra Nasreen , Liles Darla , Cabot Myles , Fisher-Wellman Kelsey
Published: September 2020

Currently there is great interest in developing cytotoxic pharmacotherapies that disrupt mitochondrial energy transduction in cancer. Given that mitochondria are critical to mammalian energy homeostasis, clinical success of a given therapeutic will undoubtedly hinge upon its cancer cell selectivity. That said, how the mitochondrial network is intrinsically remodeled to drive/enable the cancer phenotype remains a biological black box, largely due to limitations in analytical approaches. Herein, we leveraged an in-house diagnostic biochemical workflow to comprehensively evaluate mitochondrial bioenergetic efficiency and capacity in human leukemia. Using this platform, we provide direct evidence that despite minimal changes in absolute respiratory kinetics, leukemic mitochondria are hallmarked by intrinsic limitations in oxidative phosphorylation (OXPHOS) that constrain the network’s ability to contribute to cellular ATP free energy (i.e, ΔGATP) charge. Together, these findings link accelerated oxidative metabolism in leukemia to intrinsic OXPHOS deficiency and provide proof-of-concept that restoring, rather than disrupting, OXPHOS across the leukemic mitochondrial network may represent an untapped, but highly feasible, therapeutic avenue.
Ligand based 3D-QSAR pharmacophore, molecular docking and ADME to identify potential fibroblast growth factor receptor 1 inhibitors
Authors: Tang Zizhong , Huang Lu , Fu Xiaoli , Wang Haoxiang , Tang Biao , Xiao Yirong , Zhou Caixia , Zhao Zhiqiao , Wan Yujun , Chen Hui , Yao Huipeng , Shan Zhi , Bu Tongliang , Wu Xulong
Published: September 2020

Background The FGF/FGFR system may affect tumor cells and stromal microenvironment through autocrine and paracrine stimulation, thereby significantly promoting oncogene transformation and tumor growth. Abnormal expression of FGFR1 in cells is considered to be the main cause of tumorigenesis and a potential target for the treatment of cancer.Methods The known inhibitors were collected to construct 3D-QSAR pharmacophore model, which was verified by cost analysis, test set validation and Fischer test. Virtual screening of zinc database based on pharmacophore was carried out. FGFR1 crystal complex was downloaded from the protein database to dock with the compound. Finally, the absorption, distribution, metabolism and excretion (ADME) characteristics and toxicity of a series of potential inhibitors were studied.Results It was found that the constructed pharmacophore had a good ability to predict the activity. 2763 compounds in the database could hit well and the predicted activity value was less than 1 µM. Through molecular docking, we found that six compounds can bind to protein stably and inhibit the activity of FGFR1 through hydrogen bond interaction. In ADME and toxicity studies, we have successfully screened out a compound with a new structure scaffold, and found that it has good oral bioavailability and non-toxic.Conclusions This study screened out a new potential drug for cancer treatment, which can be further studied to explore its better therapeutic effect.
The Folding Propensity of α/Sulfono-γ-AA Peptidic Foldamers with Both Left- and Right-Handedness
Authors: Teng Peng , Zheng Mengmeng , Cerrato Darrell , Shi Yan , Zhou Mi , Xue Songyi , Jiang Wei , Wojtas Lukasz , Ming Li-June , Hu Yong , Cai Jianfeng
Published: September 2020

The discovery and application of new types of helical peptidic foldamers have been an attractive endeavor to enable the development of new materials, catalysts and biological molecules. To maximize their application potential through structure-based design, it is imperative to control their helical handedness based on their molecular scaffold. Herein we first demonstrate the generalizability of the solid-state right-handed helical propensity of the 413-helix of L-α/L-sulfono-γ-AA peptides that as short as 11-mer, using the high-resolution X-ray single crystallography. The atomic level folding conformation of the foldamers was also elucidated by 2D NMR and circular dichroism under various conditions. Subsequently, we show that the helical handedness of this class of foldamer is controlled by the chirality of their chiral side chains, as demonstrated by the left-handed 413-helix comprising 1:1 D-α/D-sulfono-γ-AA peptide. In addition, a heterochiral coiled-coil-like structure was also revealed for the first time, unambiguously supporting the impact of chirality on their helical handedness. Our findings enable the structure-based design of unique folding biopolymers and materials with the exclusive handedness or the racemic form of the foldamers in the future.
Effects of a ‘Baby-Friendly Hospital Initiative’ on exclusive breastfeeding rates at a private hospital in Lebanon: an interrupted time series analysis
Authors: Clermont Adrienne , Gemayel Josianne El , Hammoud Rola , Wang Jiangxia , Beciu Hortenzia , Sinno Mona , Berends Wilma , Rosenblum Nadine , Bienstock Jessica , Byrnes Kristen , Samuels Roger
Published: September 2020

Background: Exclusive breastfeeding (EBF) through six months of age has been scientifically validated as having a wide range of benefits, but remains infrequent in many countries. The WHO/UNICEF Baby-Friendly Hospital Initiative (BFHI) is one approach to improve EBF rates. Methods: This study documents the implementation of BFHI at Clemenceau Medical Center (CMC), a private hospital in Lebanon, and analyzes data on EBF practices among CMC’s patients before, during, and after the implementation period. The process of launching the BFHI at CMC is discussed from the perspective of key stakeholders using the SQUIRE guidelines for reporting on quality improvement initiatives. As an objective measure of the program’s impact, 2,002 live births from July 2015 to February 2018 were included in an interrupted time series analysis measuring the rates of EBF at discharge prior to, during, and following the bundle of BFHI interventions.Results: The steps necessary to bring CMC in line with the BFHI standards were implemented during the period between November 2015 and February 2016. These steps can be grouped into three phases: updates to hospital policies and infrastructure (Phase 1); changes to healthcare staff practices (Phase 2); and improvements in patient education (Phase 3). The baseline percentage of EBF was 2.4% of all live births. Following the BFHI intervention, the observed monthly change in EBF in the “Follow-Up” period (i.e., the 24 months following Phases 1-3) was significantly increased relative to the baseline period (+2.0 percentage points per month, p = 0.006). Overall, the observed rate of EBF at hospital discharge increased from 2.4% to 49.0% of all live births from the first to the final month of recorded data. Conclusions: Meeting the BFHI standards is a complex process for a health facility, requiring changes to policies, practices, and infrastructure. Despite many challenges, the results of the interrupted time series analysis indicate that the BFHI reforms were successful in increasing the EBF rate among CMC’s patients and sustaining that rate over time. These results further support the importance of the hospital environment and health provider practices in breastfeeding promotion, ultimately improving the health, growth, and development of newborns.​TRIAL REGISTRATION: Data collection procedures and protocols were reviewed bythe Johns Hopkins Medicine Office of Human Subjects Research Institutional Review Board (application#IRB00155989), and determined to not constitute human subjects research under DHHS or FDAregulations.
Evaluation of Antibacterial and Acute Oral Toxicity of Impatiens Tinctoria A. Rich Root
Authors: Degu Sileshi , Abebe Abiy , Gemeda Negero , Bitew Adane
Published: September 2020

Background: Infections due to a variety of bacterial etiologic agents become common and are taking the big share of morbidity and mortality. On the other way, development of antibacterial drug resistance has been commonly reported from all over the world. As a solution of stated problems scientific studies have to be conducted on the traditional medicinal plants to develop new, effective and safe antimicrobial drugs since plants are important sources. Traditionally, the study plant (I. tinctoria A. Rich) used to treat fungal infections like ring worms that cause tinea pedis and it has also different medicinal values .These were some of the provoking information to undertake the evaluation of antibacterial activities with its oral acute toxicity study. Objectives: To evaluate the antibacterial activities and acute oral toxicity of aqueous, ethanol and ethyl acetate root extracts of Impatiens tinctoria A. Rich.Methods: The roots of Impatiens tinctoria A. Rich were extracted using solvents of water, ethanol and ethyl acetate. Agar well diffusion for preliminary antibacterial screening and agar dilution methods for determination of minimal inhibitory concentration were used. The minimum bactericidal concentration of the extracts was determined. by taking inoculums from all concentrations of the plant extract plates exhibiting invisible growth (from inhibition zone of minimal inhibitory concentration plates) and subcultures onto appropriate media plate. Finally, the plant extracts were subjected to oral acute toxicity study according to the organization of economic co-operation and development test Guidelines 420. Result: Gram positive bacteria were more susceptible to the extracts compared to gram negative bacteria especially against S. aureus and S. epidermis which are commonly found in the skin even though the traditional application is to control fungal infections and to toughen the skin. Ethyl acetate extract was more potent than ethanol and aqueous extracts. The LD50 was above 9600 mg/kg.Conclusion: This study provides scientific basis as the root of I.tinctoria A.Rich had a promising antibacterial activity in extract dependent manner in which ethyl acetate extract showed better potency. Therefore, the antibacterial potential and practically non toxicness of the study plant could take the attention of scientific communities for the development of new, effective and safe antimicrobial drugs by further studying the plant in different directions.
Nanomesh-patterning on multilayer MoS2 field-effect transistors for ultra-sensitive detection of cortisol
Authors: Park Heekyeong , Baek Seungho , Jeong Bongjin , sen Anamika , Kim Sehwan , Park Yun Chang , Kim Sunkook , kim young jun
Published: September 2020

Absence of functional groups on the basal plane of molybdenum disulfide (MoS2) significantly hinders the performance of MoS2 field-effect transistor-based biosensor (bio-FET). We present a novel method for creating nano-scale holes on a MoS2 channel using block copolymer lithography, where the edge areas on the nanoholes were used to form covalent linkage between the capture molecules of cortisol aptamer and the MoS2 channel. The comparative analysis of Raman and XPS spectra well supported the formation of the nanoholes on MoS2 together with the concomitant increase in the edge area. The performance of the nanomesh bio-FET was studied by comparing its detection behavior for cortisol with that of a bio-FET manufactured with pristine MoS2. The nanomesh MoS2 bio-FET detected cortisol 109 times as low as that by the pristine MoS2 bio-FET. The selectivity of the nanomesh bio-FET was validated by detection experiments with other steroid hormones and antigens. Additionally, clinical applicability was demonstrated by performing experiments in artificial saliva and human serum.
Assessment of China’s Contribution in Regional Network for Asian Schistosomiasis: A Questionnaire Survey
Authors: Li Hongmei , Qian Yingjun , Yang Kun , Ding Wei , Huang Lulu , Ma Xuejiao , Duan Lei , Wang Duoquan , Guan Yayi , Xiao Ning , Zhou Xiao-Nong
Published: September 2020

Background The Regional Network for Asian Schistosomiasis and other Helminth Zoonoses (RNAS+) was launched 20 years ago, which has established close partnerships for counties endemic with Asian schistosomiasis and other helminthiasis, and provided an ideal regional platform for experts in the fields of control and research of parasitic diseases in Asian countries, as well as policy-making. As one of the initiating countries, China has provided significant techinal and financial supports to the regional network. This paper is to assess those contributions from China side to support the development of RNAS+.Methods An anonymous, web-based questionnaire was designed to acquire the relevant responses. The content included the basic information of respondents, China’s contributions, challenges and recommendation for the RNAS+’s development. Each participant was asked to indicate a score from 0 to 10 to assess the China’s contribution’s value, while “0” represented no contribution, and “10” was 100% contribution. The participants who leave E-mail address in the 2017 to 2019 RNAS+ annual workshops were enrolled. SPSS 20.0 was used for statistics analysis.Results A total of 71 participants enrolled, and 41 of them responded to the survey. Those were from Indonesia(n=8, 19.5%), China(n=7, 17.1%), Thailand(n=7, 17.1%), Cambodia(n=5, 12.2%), Philippines (n=4, 9.8%), Vietnam(n=3, 7.3%), Myanmar(n=2, 4.9%), Laos(n=1, 2.4%), and other 4 respondents (9.8%) were the international observers. Most of respondents are familiar with RNAS+ (34/41, 82.93%). According to the survey, China’s contribution is mainly responsible in the improving of capacity building, funding support, coordination, and cooperation programmes, and the average score of China’s contribution in the above four fields were 8.92, 8.64, 8.75, and 8.67, respectively. The overall assessment score is 8.81. The challenges of RNAS+ is lack sustainable funding and skills, and most of participants point out that they need China’s support continually.Conclusions This survey showed that China plays an important contribution in the development of RNAS+. This network-type organization on disease control and research can yet be regarded as a great potential pattern for China to enhance regional cooperation.
CS-GAN for High-Quality Diffusion Tensor Imaging
Authors: Cao Ying , Wang Lihui , Huang Jianping , Cheng Xinyu , Zhang Jian , Yang Feng , Zhang Pengpeng , Yang Jie , Zhu Yueming
Published: September 2020

Background: Compressed sensing magnetic resonance imaging (CS-MRI) is a promising technique for accelerating MRI speed. However, image quality in CS-MRI is still a pertinent problem. In particular, there is little work on reducing aliasing artefacts in compressed sensing diffusion tensor imaging (CS-DTI), which constitute a serious obstacle to obtaining high-quality images. Method: We propose a CS-DTI de-aliasing method based on conditional generative adversarial (cGAN), called CS-GAN, to tackle de-aliasing problems in CS-DTI with highly undersampled k-space data. The method uses a nested-UNet based generator, a ResNet-based discriminator, and a content loss function defined in both image domain and frequency domain. Result and Concludions: Compared to existing state-of-the-art de-aliasing methods based on deep learning, our method achieves superior imaging quality in terms of both diffusion weighted (DW) image quality and DTI diffusion metrics. Moreover, even at extremely low sampling ratio and low SNR, our method can still reconstruct texture details and spatial information.
Serum alanine aminotransferase activity is age- and sex-depended but independently predicted by body mass index in both sexes. The Tromsø study
Authors: Bekkelund Svein Ivar
Published: September 2020

Background

High and low levels of serum alanine aminotransferase (ALT) are associated with cardiovascular diseases (CVD) especially in elderly but the roles of sex and age are unexplained. This study investigated sex- and age-related variation of serum ALT and associations between ALT and CVD risk factors in men and women in a Caucasian population.
Methods

This study used cross-sectional data from Tromsø 6 in 2555 men (mean age 60.4 years) and 2858 women (mean age 60.0 years). Associations were assessed by variance analysis and multivariable logistic regression of odds to have abnormal ALT.
Results

Abnormal ALT was detected in 113 (4.4%) men and 188 (6.6%) women. ALT correlated negatively with age in men (r = -0.231, p < 0.001) and positively in women (r = 0.124, p < 0.001). A linear inversed association between age and ALT in men and a non-linear inversed U-trend in women with maximum level between 60–64 years were found. Age was independently associated with ALT in men only [OR 1.05 (95% CI 1.04, 1.07), p < 0.001] and body mass index (BMI) was independently associated with ALT in both sexes.
Conclusion

The relationship between age and ALT was opposite directed in men compared to women, and linearly and independently in men only. Neither BMI as the strongest associated CVD risk factor in both sexes nor other risk components could explain this. Separate sex-analyses should be used in studies investigating the role of ALT as a disease marker.
Secondary Infertility: A Neglected Aspect of Buerger’s Disease
Authors: Ziaeemehr Aghigh , Sharebiani Hiva , Taheri Hossein , Fazeli Bahare
Published: September 2020

Aim: During the gathering of demographic data for the biobank on Buerger’s Disease (BD), we found that, after the clinical manifestation of BD, the patients usually became infertile, and the age of their last child was compatible with the time of disease diagnosis. The aim of this study was to evaluate the underlying cause of secondary infertility in BD patients.Method: Anti-sperm antibodies (ASA), testosterone, luteinising hormone (LH), and follicle-stimulating hormone (FSH) in the sera of 39 male BD patients were measured and compared with 39 age-matched Caucasian male controls.Results: Six patients declared that they suffered from impotency. The ASA level was positive in 25.6% of the patients and 2.4% of the controls (p = 0.003, CC = 6.96). The mean levels of testosterone in the patients and controls were 393.12 ± 32.9ng/dl and 354.37 ± 30.9ng/dl, respectively. The mean levels of LH in the patients and controls were 0.88 ± 0.12mIU/r and 0.85 ± 0.1mIU/r, respectively. The mean levels of FSH in the patients and controls were 4.1 ± 0.35mIU/r and 3.56 ± 0.33mIU/r, respectively. No significant difference in the serum levels of testosterone, LH, or FSH was found between the patients and controls (p > 0.05). The spermograms of three ASA-negative patients demonstrated impaired sperm motility.Conclusion: Anti-sperm antibodies, disturbed genital circulation, autonomic dysfunction and sperm motility may be responsible for secondary infertility in Buerger’s Disease. Ethical code: MUMS-941842
Powdered over fresh milk preference and hygienic dairy practices in Sri Lanka
Authors: Rupasinghe Ruwini , Morey Ryen , Michele Miller , Manoji Achala , Salgado Ayesha , Jinadasa Rasika , Smith Woutirna , Wickramasinghe Saumya
Published: September 2020

Background

The majority of Sri Lankans may select imported powdered milk over fresh milk, and a significant portion of Gross Domestic Product in Sri Lanka is spent on dairy products imports. Demand for fresh milk may be hindered by consumer preference towards powdered milk consumption and the lack of hygienic standards for fresh milk. The current study was conducted to identify factors contributing to consumer preference for powdered milk and to evaluate hygienic best practices of dairy farms.
Methods

The study took place in Kandy district, Sri Lanka. Two surveys were conducted: the first survey included questions concerning demographics and reasons for milk preference was administered to a randomly selected population (n = 561); the second survey focused on hygienic practices in dairy farms, and was administered to owners of dairy farms (n = 195). Milk samples were collected from individual cows and bulk tanks and analyzed for coliform counts. Regression approaches were used to evaluate associations of demographic variables with milk preference, farm management practices with mastitis history, and coliform counts.
Results

A large consumer preference was observed for powdered milk (86%), and females were 2.2 times more likely to select powdered milk than males (P = 0.03). Availability was the main reason for powdered milk preference, whilst taste was the main reason for selecting fresh milk. Coliform counts were higher in most of the analyzed bulk milk samples and rinsing bulk milk tanks with warm water showed a significant reduction in milk coliform counts. Washing the teats with warm water had a lower mastitis risk when compared to washing teats with regular water.
Conclusions

Study revealed that in order to create a fresh milk drinking culture in Sri Lanka there needs to be a mechanism to make it more accessible to the consumers. Fresh milk marketing strategies need to be focused more on the female consumers. Farmer education on good hygienic practices, elimination of inefficiencies in both milk production and collection process, standardization of milk quality according to the number of microorganisms in milk would improve the quality of dairy products in Sri Lanka.
Polygenic risk score for early prediction of sepsis risk in the polytrauma screening cohort
Authors: Lu Hongxiang , Wen Dalin , Sun Jianhui , Du Juan , Qiao Liang , Zhang Huacai , Zeng Ling , Zhang Lianyang , Jiang Jianxin , Zhang Anqiang
Published: September 2020

Background: Increasing genetic variants associated with sepsis have been identified by candidate-gene and genome-wide association studies, but single variant conferred minimal alterations in risk prediction. Our aimed to evaluate whether a weighted genetic risk score (wGRS) that aggregate information from multiple variants could improve risk discrimination of traumatic sepsis.Methods: 64 genetic variants potential relating to sepsis were genotyped in Chinese trauma cohort. Genetic variants with mean decrease accuracy (MDA) > 1.0 by random forest algorithms were selected to construct the multilocus wGRS. Area under curve (AUC) and Net reclassification improvement (NRI) were adopted to evaluate the discriminatory and reclassification ability of wGRS.Results: Seventeen variants were extracted to construct the wGRS in 883 trauma patients. The wGRS was significantly associated with sepsis after trauma (OR = 2.19, 95%CI = 1.53–3.15, P = 2.01 × 10− 5) after adjusted by age, sex, and ISS. Patients with higher wGRS have an increasing incidence of traumatic sepsis (Ptrend=6.81 × 10− 8), higher SOFA (Ptrend=5.00 × 10− 3) and APACHE II score (Ptrend=1.00 × 10− 3). The AUC of risk prediction model incorporating wGRS into the clinical variables was 0.768 (95%CI = 0.739–0.796), with an increase of 3.40% (P = 8.00 × 10− 4) versus clinical factors-only model. Furthermore, the NRI increased 25.18% (95%CI = 17.84–32.51%) (P = 6.00 × 10− 5).Conclusions: Our finding indicated that genetic variants could enhance the predictive power of risk model for sepsis and highlighted the application among trauma patients, suggesting that the sepsis risk assessment model will be a promising screening and prediction tool for high risk population.
Self-reported psychological disorders among the mothers of children with an autism spectrum disorder, type 1 diabetes mellitus, and typically developed children
Authors: Al-Ansari Ahmed Malalla , Janahi Mohammed Ismail , AlTourah Abdulrahman Jamal , Jahrami Haitham Ali , Rajab Mansour Bin
Published: September 2020

ObjectivesTo assess the prevalence of symptoms of depression, anxiety, and stress among mothers of children of autism spectrum disorders (ASD), type 1 diabetes, and typically developed (TD).Method. The study sample comprised mothers of children with ASD ( Group 1; n = 116), diabetes mellitus (Group 2; n = 43 ), and a control group of mothers with TD children.ResultsBoth groups 1 and 2 had higher scores of depression (37.86), anxiety (4.58), and stress (29.81) in DASS-21 in comparison to control (P = 0.015). On PSS-14 The mean score on PSS-14 were: group 1 (27.61), group 2 (28.63) and control (25.87) (p = 0.004). Group 1 scored higher scores for depression domain (p = 0.046) whereas group 2 for anxiety domain (p = 0.034) and stress domain (p = 0.009) in comparison to TD group on DASS-21.ConclusionMothers of children with ASD should be assessed for the presence of depression following diagnosis. Mothers of children with type 1 diabetes required careful monitoring for the effects of anxiety and stress on their mental health, therefore their ability to cope with a management plan.
Assessment of Lymphocytosis in Patients with Pertussis in the Amhara Regional State, Ethiopia
Authors: Taye Solomon , Tessema Belay , Gelaw Baye , Moges Feleke
Published: September 2020

Background: Pertussis is a severe and prolonged coughing disease caused by Bordetella pertussis. In 2014, an estimated 24.1 million pertussis cases, resulting in 160,700 deaths were reported worldwide. The aim of this study was to assess lymphocytosis in patients with pertussis in the Amhara Regional State, Ethiopia.Methods: An institution-based cross-sectional study was conducted among pertussis patients who met the clinical case definition for pertussis in the Amhara Regional State, Ethiopia. The study was conducted from July 2018 to February 2019 and nasopharyngeal swabs were collected from 321 participants, and samples were analyzed using real-time PCR. Blood specimens were collected from 321 study participant and total lymphocyte count was conducted using fully automated haematology analyzer.Results: One hundred nine study participants were positive for Bordetella species. Lymphocytosis was found in 15/109 (13.8%) of the PCR confirmed pertussis patients. Of those 15 PCR confirmed participants, 53.3% had lymphocytosis grading ‘high’ (>51%) followed by 20% ‘moderately high’ (>70%) and 26.7% had ‘very high’ (>85%). Amongst participants with lymphocytosis and PCR confirmed pertussis, 11/15 (73.3%) were less than 1 year old.Conclusions: This study revealed the importance of lymphocyte count in the diagnosis of pertussis. Thus, in combination with other laboratory tests, incorporation of lymphocyte count in pertussis suspected patients is recommended.
Pulmonary Hemodynamics and Ventilation in Patients With COVID-19-related Respiratory Failure and ARDS
Authors: Becker André , Seiler Frederik , Muellenbach Ralf M. , Danziger Guy , Mang Sebastian , Omlor Albert , Jentgen Christophe , Kamphorst Maren , Wehrfritz Holger , Lotz Christopher , Mertke Thilo , Wilkens Heinrike , Bals Robert , Lepper Philipp M.
Published: September 2020

Background: It has been suggested that COVID-19-associated severe respiratory failure (CARDS) might differ from usual acute respiratory distress syndrome (ARDS) due to failing auto-regulation of pulmonary vessels and higher shunt. We sought to investigate pulmonary hemodynamics and ventilation properties in patients with CARDS compared to patients with ARDS of pulmonary origin. Methods: Retrospective analysis of prospectively collected data of consecutive adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 patients treated on our ICU in 04/2020 and comparison of the data to matched controls with ARDS due to respiratory infections treated on our ICU from 01/2014 to 08/2019 and for whom pulmonary artery catheter data were available. Results: CARDS patients (n = 10) had similar ventilation characteristics as compared to ARDS (n = 10) patients. Still, mechanical power applied by ventilation was significantly higher in CARDS patients (23.4 ± 8.9 J/min) than in ARDS (15.9 ± 4.3 J/min; p<0.05). COVID-19 patients had similar pulmonary artery pressure but significantly lower pulmonary vascular resistance, as cardiac output was higher in CARDS vs. ARDS patients (p<0.05). Shunt fraction and dead space were similar in CARDS compared to ARDS (p>0.05) and was in both groups correlated with hypoxemia. The arterio-venous pCO2 difference (DpCO2) was elevated (CARDS 5.5±2.8 mmHg vs. ARDS 4.7±1.1 mmHg; p>0.05) as was P(v-a)CO2/C(a-v)O2 ratio (CARDS mean 2.2±1.5 vs. ARDS 1.7±0.8; p>0.05). Conclusions: Respiratory failure in COVID-19 patients seems to differ only slightly from ARDS regarding ventilation characteristics and pulmonary hemodynamics. Differences are mainly due to increased CO2 production in CARDS patients. Our data indicate microcirculatory dysfunction. More data needs to be collected to assure these findings and gain more pathophysiological insights in COVID-19 and respiratory failure.
Clinical Course and Risk Factors for Liver Injury of Severe and Critical Patients With COVID-19: A Single-centered, Retrospective, Observational Study
Authors: Liu Jingyuan , Du Chunjing , Yang Siyuan , Pu Lin , Xiang Pan , Li Ang
Published: September 2020

Background: The information regarding the clinical course of COVID-19 patients with liver injury is very limited, especially in severe and critical patients. The objective of this study was to describe the characteristics and clinical course of patients admitted with severe and/or critical SARS-CoV-2 infection in liver function, as well as explore the risk factors that affect liver function in the enrolled COVID-19 patients.Methods: Information on clinical characteristics of 63 severe and critical patients with confirmed COVID-19 were collected and analyzed.Results: The incidence of abnormal aspartate aminotransferase, alanine aminotransferase, and total bilirubin in the critical group was obviously higher than in the severe group (81.48%, 81.49%, 62.67%, and 45.71%, 63.88%, 22.86%, respectively, p＜0.05). The time for liver parameters to reach their peak or trough was approximately 2-3 weeks. No significant difference was observed in cycle threshold values of open reading frame 1ab and nucleocapsid protein gene on admission or at the peak among liver injury group, abnormal group and normal group (p＞0.05). Patients with invasive ventilator, decreased percentage of neutrophil, lymphocyte and monocyte, and SOFA score ≥ 2 (p＜0.05) were the independent factors associated with liver injury.Conclusions: Abnormal liver tests are commonly observed in severe and critical patients with COVID-19. The time of 2-3 weeks after admission should be paid attention to patients with critical COVID-19 in case of the occurrence of liver injury. As independent risk factors for the occurrence of liver injury, regarding decreased ratio of neutrophils, lymphocytes and monocytes, the requirement of invasive ventilator, and SOFA score ≥2 , patients with these abnormal parameters should be of particular concerned during hospitalization.
Fecal microbiota Profiling in Irritable Bowel Syndrome and Inflammatory Bowel Disease Patients with Irritable Bowel Syndrome-Type Symptoms
Authors: Cui Xiufang , Wang Haiyang , Ye Ziping , Li Yi , Qiu Xinyun , Zhang Hongjie
Published: September 2020

BACKGROUND
The intestinal microbiota is thought to be involved in the occurrence of Inflammatory Bowel Disease in remission (IBDR) with Irritable Bowel Syndrome (IBS)-type symptoms, but the specific distinct profile of these bacteria remains unclear. Therefore, the purpose of this research is to investigate this issue by conducting a cross-sectional study.
METHODS
IBS patients were diagnosed according to Rome Ⅳ criteria, IBD diagnosed according to the criteria of European Crohn & Colitis Organization (ECCO), IBDR patients with IBS-type symptoms were defined according to related IBS-type symptoms meeting the Rome IV criteria in IBDR patients, and were included Crohn’s disease in remission (CDR) and ulcerative colitis in remission (UCR) based on Crohn’s Disease Activity Index (DAI) and Mayo Scoring System respectively. Healthy controls come from the physical examination center and exclude people with underlying diseases. All enrolled subjects were divided into six groups, as followed: Health Control, IBS, CDR with IBS-type symptoms (CDR-IBS+), CDR without IBS-type symptoms (CDR-IBS−), UCR-IBS+ and UCR-IBS−. We collected fresh fecal samples from all subjects and applied 16S rRNA sequencing analysis to detect the structure and diversity of the microbiota among different groups.
RESULTS
A total of 97 subjects were included in this study, of which 18 were health controls, 34 IBS patients, 25 CDR and 20 UCR. The richness of intestinal microbiota in CDR-IBS−was significantly lower than that in the control and IBS groups based on the analysis of observed species and Chao index (P < 0.05). The observed species index in CDR-IBS+ was significantly higher than CDR-IBS− group (median index: 254.8 vs 203, P = 0.036). No difference was found in Alpha diversity between UCR-IBS+ and UCR-IBS−. At phylum level, there was no significant difference between UC or CD with IBS-type symptoms and those without related symptoms. At genus level, the number of Faecalibacterium in CDR-IBS+ increased significantly while Fusobacterium decreased compared with CDR-IBS−(mean relative abundance of Faecalibacterium: 20.35% vs 5.18%, P < 0.05; Fusobacterium: 1.51% vs 5.2%, P < 0.05). However, compared with UCR-IBS - group, the number of Faecalibacterium in UCR-IBS + group decreased, while the number of Streptococcus increased, but there was no statistical difference in the genus structure. Regardless of the phylum or genus level, the abundance and composition of the microbiota of IBS patients were not distinct from those of healthy people.
CONCLUSIONS
CD patients in remission with IBS-type symptoms may be related to the increase of Faecalibacterium and decrease of Fusobacterium. UC patients in remission with IBS-type symptoms cannot be explained by changes in the abundance and structure of intestinal microbiota from our across-sectional study.
Intention to immigration and its relationship with workload and healthy work environment in nurses
Authors: Salehinia Nadia , Salehi Tahmine , Haghani Shima
Published: September 2020

Background The immigration of nurses in Iran is increasing day by day, and it seems work-related factors such as workload and healthy work environment are associated with the intention to immigration.Objectives this study was conducted to determine the intention to immigration in nurses and its relationship with workload and healthy work environment.Methods This cross-sectional, descriptive-correlational study was conducted in 2020 by simple random sampling method of 360 nurses working in hospitals in Iran. The study instruments were questionnaires of demographics, Intention to immigration (Lee, 2016), Workload (NASA-TLX) and healthy work environment (AACN, 2005). Data were analyzed by SPSS software and descriptive tests. p value < 0.05 was considered statistically significant.Results The score of intention to immigration was 65.59%, which indicated a high level of intention to immigration in nurses. There was a significant but weak correlation between intention to immigrate, with workload (r = 0.166, p = 0.002) and healthy work environment (r = 0.16, p = 0.002).Conclusion there was a weak but important relationship between the intention to immigration, workload and healthy work environment. More studies on factors related to the intention to immigration are required.
The effect of combined transcranial pulsed current stimulation and transcutaneous electrical nerve stimulation on lower limb spasticity in children with spastic cerebral palsy classified on Gross Motor Function Classification System (GMFCS) levels III–V: a randomized and controlled clinical study
Authors: Liu Zhen Huan , Dong Shangsheng , Zhang Chuntao , Zhou Yuan , Huang Fang , Deng Haorong
Published: September 2020

BackgroundIn the current study, we applied a combination of non-invasive neuromodulation modalities concurrently with multiple stimulating electrodes. Specifically, we used transcranial pulsed current stimulation (tPCS) and transcutaneous electrical nerve stimulation (TENS) as a novel strategy for improving lower limb spasticity in children with spastic cerebral palsy (SCP) categorized on levels III–V of the Gross Motor Function Classification System (GMFCS) with minimal side effects.Methods63 SCP children aged 2–12 years who were classified on levels III–V of the GMFCS were randomly assigned to one of two groups, resulting in 32 children in the experimental group and 31 children in the control group. The experimental group underwent a combination therapy of tPCS (400 Hz, 1 mA cerebello-cerebral stimulation) and TENS (400 Hz TENS, max 10 mA) for 30 min, followed by 30 min of physiotherapy daily for 12 weeks. The control group underwent physiotherapy only 30 mins per day for 12 weeks. In total, all groups underwent 60 treatment sessions. The primary outcome measures were the Modified Ashworth Scale (MAS) and Modified Tardieu Scale (MTS). Evaluations were performed three days before and after treatment.ResultsWe found a significant improvement in MAS and MTS scores of the lower limbs in the experimental group compared to the control group in the hip adductors (Left: p = 0.002; Right: p = 0.002), hamstrings (Left: p = 0.001; Right: p < 0.001, and gastrocnemius (Left: p = 0.001; Right: p = 0.000). Moreover, MTS scores of R1, R2 and R2-R1 in left and right hip adduction, knee joint, and ankle joint all showed significant improvements (p £ 0.05). Analysis of MAS and MTS scores compared to baseline scores showed significant improvements in the experimental group but declines in the control group.ConclusionThese results are among the first to demonstrate that a combination of tPCS and TENS can significantly improve lower limb spasticity in SCP children classified on GMFCS levels III–V with minimal side effects, presenting a novel strategy for addressing spasticity challenges in children with severe SCP.Trial registration: ChiCTR.org, ChiCTR1800020283, Registration22 December 2018, (URL: http://www.chictr.org.cn/edit.aspx?pid=33953&htm=4).
OsPG1 encodes a polygalacturonase that determines cell wall architecture and affects resistance to bacterial blight pathogen in rice
Authors: Liu Qunen , Cao Yongrun , Zhang Yue , Chen Yuyu , Yu Ning , Liaqat Shah , Wu Weixun , Chen Daibo , Cheng Shihua , Wei Xinghua , Cao Liyong , Zhang Yingxin
Published: September 2020

Background Plant cell walls are the main physical barrier encountered by pathogens colonizing plant tissues. Alteration of cell wall integrity (CWI) can activate specific defenses by impairing proteins involved in cell wall biosynthesis, degradation and remodeling, or cell wall damage due to biotic or abiotic stress. Polygalacturonase (PG) depolymerize pectin by hydrolysis, thereby altering pectin composition and structures and activating cell wall defense. Although many studies of CWI have been reported, the mechanism of how PGs regulate cell wall immune response is not well understood.Results Necrosis appeared in leaf tips at the tillering stage, finally resulting in 3–5 cm of dark brown necrotic tissue. ltn-212 showed obvious cell death and accumulation of H2O2 in leaf tips. The defense responses were activated in ltn-212 to resist bacterial blight pathogen of rice. Map based cloning revealed that a single base substitution (G-A) in the first intron caused incorrect splicing of OsPG1, resulting in a necrotic phenotype. OsPG1 is constitutively expressed in all organs, and the wild-type phenotype was restored in complementation individuals and knockout of wild-type lines resulted in necrosis as in ltn-212. Transmission electron microscopy showed that thicknesses of cell walls were significantly reduced and cell size and shape were significantly diminished in ltn-212.Conclusion These results demonstrate that OsPG1 encodes a PG in response to the leaf tip necrosis phenotype of ltn-212. Loss-of-function mutation of ltn-212 destroyed CWI, resulting in spontaneous cell death and an auto-activated defense response including reactive oxygen species (ROS) burst and pathogenesis-related (PR) gene expression, as well as enhanced resistance to Xanthomonas oryzae pv. oryzae (Xoo). These findings promote our understanding of the CWI mediated defense response.