bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling the β-secretase cleavage site and humanizing amyloid-beta precursor protein in rat and mouse to study Alzheimer’s Disease.
Authors: Serneels Lutgarde , T'Syen Dries , Perez-Benito Laura , Theys Tom , Holt Matthew G , De Strooper Bart 
Published: August 2020

Abstract
BackgroundThree amino acid differences between rodent and human APP affect medically important features, including β-secretase cleavage of APP and Aβ peptide aggregation(1–3). Most rodent models for Alzheimer’s disease (AD) are, therefore, based on the human APP sequence, expressed from artificial mini-genes randomly inserted in the rodent genome. While these models mimic rather well various biochemical aspects of the disease, such as Aβ-aggregation, they are also prone to overexpression artifacts and to complex phenotypical alterations, due to genes affected in or close to the insertion site(s) of the mini-genes(4,5). Knock-in strategies which introduce clinical mutants in a humanized endogenous rodent APP sequence(6) represent useful improvements, but need to be compared with appropriate humanized wildtype (WT) mice. MethodsComputational modelling of the human β-CTF bound to BACE1 was used to study the differential processing of rodent and human APP. We humanized the three pivotal residues we identified G676R, F681Y and R684H (labeled according to the human APP770 isoform) in the mouse and rat genomes using a CRISPR-Cas9 approach. These new models, termed mouse and rat Apphu/hu, express APP from the endogenous promotor. We also introduced the early-onset familial Alzheimer’s disease (FAD) mutation M139T into the endogenous Rat Psen1 gene.ResultsWe show that introducing these three amino acid substitutions into the rodent sequence lowers the affinity of the APP substrate for BACE1 cleavage. The effect on β-secretase processing was confirmed as both humanized rodent models produce three times more (human) Aβ compared to the original WT strain. These models represent suitable controls, or starting points, for studying the effect of transgenes or knock-in mutations on APP processing(6). We introduced the early-onset familial Alzheimer’s disease (FAD) mutation M139T into the endogenous Rat Psen1 gene and provide an initial characterization of Aβ processing in this novel rat AD model.Conclusion The different humanized APP models (rat and mouse) expressing human Aβ and PSEN1 M139T are valuable controls to study APP processing in vivo allowing the use of a human Aβ ELISA which is more sensitive than the equivalent system for rodents. These animals will be made available to the research community.
On the theoretical prediction of microalgae growth for parallel flow
Authors: Ma Chunyang 
Published: August 2020

Abstract
Background: The established microalgae growth models are semi-empirical or considerable fitting coefficients exist. Therefore, the ability of the model prediction is reduced by the numerous fitting coefficients. Furthermore, the predicted results of the established models are dependent on the size of the photobioreactor (PBR), light intensity, flow and concentration field. The growth mechanism of microalgae has not clearly understood in PBR cultivation. It is difficult to predict the microalgae growth by theoretical methods, owing to the aforementioned factors. We developed an exploratory bridging microalgae growth model to predict the microalgae growth rate in PBRs by using the nondimensional method which is effectively in fluid dynamics and heat transfer. Results: The analytical solution of the growth rate was obtained for the parallel flow. The nondimensional growth rate expressed as function of Reynolds number and Schmidt number, which can be used for arbitrary parallel flow due to the solution was expressed as nondimensional quantities. The theoretically predicted growth rate is compared with the experimentally measured microalgae growth rate on the order of magnitude. Conclusions: The nondimensional method successfully applied to the microalgae growth problem for the first time. The general nondimensional solution can unify the numerous experimental data for different laboratory conditions, and give a direction for the disorder of the microalgae growth problem. The nondimensional solution will be useful in the design and operation of PBRs for biofuel production.
IPSE, a Urogenital Parasite-Derived Immunomodulatory Molecule, Suppresses Bladder Pathogenesis and Anti-Microbial Peptide Gene Expression in Bacterial Urinary Tract Infection
Authors: Mbanefo Evaristus C. , Le Loc , Pennington Luke F. , Hsieh Yi-Ju , Odegaard Justin I. , Lapira Kristina , Jardetzky Theodore S. , Falcone Franco H. , Hsieh Michael 
Published: August 2020

Abstract
Background: Parasitic infections can increase susceptibility to bacterial co-infections. This may be true for urogenital schistosomiasis and bacterial urinary tract co-infections (UTI). We previously reported that this co-infection is facilitated by S. haematobium eggs triggering interleukin-4 (IL-4) production and sought to dissect the underlying mechanisms. The interleukin-4 inducing principle from Schistosoma mansoni eggs (IPSE) is one of the most abundant schistosome egg-secreted proteins and binds to IgE on the surface of basophils and mast cells to trigger IL-4 release. IPSE can also translocate into host nuclei using a nuclear localization sequence (NLS) to modulate host transcription. We hypothesized that IPSE is the factor responsible for the ability of S. haematobium eggs to worsen UTI pathogenesis. Methods: Mice were intravenously administered a single 25 mg dose of recombinant S. haematobium-derived IPSE, an NLS mutant of IPSE or PBS. Following IPSE exposure, mice were serially weighed, and organs analyzed by histology to assess for toxicity. Twenty-four hours after IPSE administration, mice were challenged with the uropathogenic E. coli strain UTI89 by urethral catheterization. Bacterial cfu were measured using urine. Bladders were examined histologically for UTI-triggered pathogenesis and by PCR for antimicrobial peptide expression.Results: Unexpectedly, IPSE administration did not result in significant differences in urine bacterial CFU. However, IPSE administration did lead to a significant reduction in UTI-induced bladder pathogenesis and the expression of anti-microbial peptides in the bladder. Despite the profound effect of IPSE on UTI-triggered bladder pathogenesis and anti-microbial peptide production, mice did not demonstrate systemic ill effects from IPSE exposure.Conclusions: Our data show that IPSE may play a major role in S. haematobium-associated urinary tract co-infection, albeit in an unexpected fashion. These findings also indicate that IPSE either works in concert with other IL-4-inducing factors to increase susceptibility of S. haematobium-infected hosts to bacterial co-infection, or does not contribute to enhancing vulnerability to this co-infection.
Association between functional disability and depressive symptoms among older adults in rural China: a cross-sectional study
Authors: Rong Jian , Ge Yanhong , Wang Xueqin , Chen Guimei , Ding Hong 
Published: August 2020

Abstract
Background: The association between functional disability and depressive symptoms among elderly people in rural China is not clear. This study explored the relationship between functional disability and depressive symptoms, focusing on whether an interactive association between functional disability, demographic characteristics and depressive symptoms exists among older adults in rural Anhui, China.Methods: A cross-sectional survey study was conducted with multi-stage stratified random sampling. The 30-item Geriatric Depression Scale and WHO Disability Assessment Schedule 2.0 were used to evaluate depressive symptoms and functional disability, respectively. The data were analyzed using SPSS statistics 25.0 program with chi-square test, Mann-Whitney U test, binary logistic regression analysis, and classification and regression tree model.Results: The prevalence of depressive symptoms in 3336 older people was 52.94%. After adjustment, subjects who had problems in participation (adjusted odds ratio [AOR]=3.499, 95% confidence interval [CI]: 2.385-4.987), life activities (AOR=1.683, 95% CI: 1.370-2.066), getting along (AOR=1.616, 95% CI: 1.299-2.010), and mobility (AOR=1.842, 95% CI: 1.503-2.258) had an increased depressive symptoms risk. However, cognition (AOR=0.785, 95% CI: 0.647-0.953) negatively correlated with depressive symptoms. Additionally, the interactive association between functional disability dimensions, various variables and depressive symptoms were identified for the first time. Those who had problems in mobility, getting along and were unemployed, the possibility of having depressive symptoms was the highest.Conclusions: Special attention should be paid to unemployed older adults, and those with problems in participation, life activities, getting along, and mobility and no problems in cognition to maintain a good psychological state. Our findings may be greatly significant for developing more targeted and effective mental health prevention and intervention measures for older adults in rural areas.
Bone mineral density reference values in Singaporean adults and comparison for osteoporosis establishment – The Yishun Study
Authors: Chen Kexun , Wee Shiou-Liang , Pang Benedict Wei Jun , Lau Lay Khoon , Jabbar Khalid Abdul , Seah Wei Ting , Sriniva Sivasubramanian , Mallya Jagadish Ullal , Ng Tze Pin 
Published: August 2020

Abstract
Background

While there have been studies in Singapore on the prevalence and economic burden of osteoporotic hip fracture, there is a severe lack of reference data on bone mineral density and prevalence of osteoporosis. The purpose of this study is to establish the reference values for BMD and compare prevalence of osteoporotic conditions using other available reference values so as to better understand the status of bone health in Singaporean adults.

Methods

We carried out a population-based cross-sectional study using dual-energy x-ray absorptiometry (Hologic Discovery Wi) to measure the bone mineral density of Singaporean adults aged [[EQUATION]] 21 years. 314 women and 223 men were recruited from the large north-eastern residential town of Yishun. ﻿We computed T-scores (denoted by T SG ) for each individual in the study. Similar diagnoses were also done based on T-scores provided by the densitometer (T DXA ), NHANES database (T NHANES ), and China (T CHN ), and the differences in prevalence compared. We then compared the concordance between T SG and T DXA in the classification of osteoporosis. Osteoporosis was defined according to criteria by the World Health Organization (WHO).

Results

Peak lumbar spine BMD was 1.093±0.168g/cm 2 in women, and 1.041±0.098g/cm 2 for men. Peak whole-body BMD was 1.193±0.93g/cm 2 in women at, and 1.224±0.112g/cm 2 for men. Prevalence of osteoporosis based on lumbar spine was 9.3% in postmenopausal women, and 0.7% in men after 50 years of age. The percentage difference in prevalence range from 60.5 - 163.6%, when using reference values from T DXA , T NHANES , and T CHN . Comparing diagnosis using T DXA and T SG cut-off values, 28 versus 15 women were diagnosed as osteoporotic respectively. ﻿ The kappa statistics was 0.81 for women and 0.85 for men.

Conclusion

Our study shows that T-scores provided by DXA manufacturer over-diagnosed osteoporosis in Singaporeans, and the prevalence of osteoporotic conditions is not accurately represented. This over-diagnosis may result in unnecessary treatment in some individuals.
Bacteriological Quality of Raw Meat, Antibiotic Susceptibility Pattern of Bacterial Isolation and Associated Risk Factors Among Butcher Houses of Adama Town, Oromia, Ethiopia, 2020
Authors: Abebe Aschalew , Arero Godana , Shiferaw Teklu 
Published: August 2020

Abstract
BackgroundFoodborne diseases continue to be an important public health problem globally and most of the food safety hazards are caused by foods of animal sources. It is also reported that contaminated raw meat has been identified as one of the main sources of foodborne illnesses. In Ethiopia, the widespread habit of raw meat consumption, lack of compliance with standard quality and sanitation protocols is a potential cause for foodborne illnesses. The purpose of this study was to assess bacteriological quality, antibiotic susceptibility pattern of bacterial isolation of raw meat and associated factors among butcher houses of Adama town, Ethiopia, 2019. ResultsThree-fourth (¾th) of collected raw meat was unacceptable bacterial load of Total Aerobic Plate count based on Gulf Standard. The average contamination was (5.89±0.86) log Colony Forming Unit per gram for total aerobic plate count. Raw meat collected from meat handlers who trained on meat hygiene (AOR=5.8, 95%CI:(1.99-17.34), collecting money (AOR= 0.14,95%CI (0.04-0.43) were associated with bacteriological quality of raw meat. Whereas, proportion of meat samples that were positive for Salmonella and shigella were (9.8% and 2.67%) respectively. The resistance of Salmonella was most frequently observed to Ampicillin (100%), Amoxicillin/ Clavunilic (54.5%), Tetracycline (36.3%) Trimethoprim-sulfamethoxazole (18.2%). Shigella expressed resistance to Ampicillin (50%) and 100% sensitive to the rest antibiotics used.ConclusionBacterial logarithmic mean values were beyond the acceptable standard indication of poor hygiene, making it a potential source of food-borne infection. Therefore, stringent inspection, regular supervision, training and hygienic practices should be introduced to enhance hygienic quality meat for consumers.
Burnout Syndrome and Its Predictors in Dermatology Residents
Authors: Shadid Asem , Aldosari Batal M , ALGarni Abdullah M , Altalhab Saad , Alharithy Ru’aa 
Published: August 2020

Abstract
Background: Burnout is a problem that is highly under-reported and under-recognized. Defined by three dimensions: emotional exhaustion (EE), cynicism or depersonalization (DP), and low personal feelings of achievement (PA). It is a prolonged response to chronic emotional and interpersonal stressors on the job. If unrecognized, the costs to the healthcare providers and to the health care system can be enormous. Previous studies reported various burnout rates during board training programs; yet, none focused on dermatology residents. This is the first study to assess burnout rate and possible predictors in dermatology residents in the middle east, and the second worldwide.Methods: The Maslach Burnout Inventory, alongside the possible risk factors of burnout, was distributed to dermatology board training programs in all affiliated centers in Riyadh, Saudi Arabia, yielding a response rate of 96.2%.Results: High EE was present in 41.2% of dermatology residents, a low sense of PA was present in 45.1%, while high DP was the least prevalent at 13.7%. Satisfaction with career was significantly associated with high risk of EE (OR = 0.61, P < 0.001), high risk of DP (OR = 0.34, P = 0.001) and low risk of PA (OR = 0.68, P < 0.001). The average number of sleeping hours was also associated with high risk of EE (OR = 0.87, P < 0.001), high risk of DP (OR = 0.76, P = 0.001) and low risk of PA (OR = 0.86, P < 0.001). Our findings report high burnout in 7.8% of the respondents.Conclusions: The burnout phenomenon is a well-known issue that must be acknowledged by program directors in academic medicine. Protected time to pursue academic interests, e.g., research and teaching, and a fair distribution of on-call hours per month, as well as a number of clinics per week may explain the rate of burnout in our study. These findings can be applied in the development and improvement of training programs to reduce the burnout rate among future dermatologists.
Nothing wrong about change: The adequate choice of the dependent variable and design in prediction of cognitive training success
Authors: Mattes André , Roheger Mandy 
Published: August 2020

Abstract
Background Even though investigating predictors of intervention success (e.g Cognitive Training, CT) is gaining more and more interest in the light of an individualized medicine, results on specific predictors of intervention success in the overall field are mixed and inconsistent due to different and sometimes inappropriate statistical methods used. Therefore, the present paper gives a guidance on the appropriate use of multiple regression analyses to identify predictors of CT and similar non-pharmacological interventions.Methods We simulated data based on a predefined true model and ran a series of different analyses to evaluate their performance in retrieving the true model coefficients. The true model consisted of a 2 (between: experimental vs. control group) x 2 (within: pre- vs. post-treatment) design with two continuous predictors, one of which predicted the success in the intervention group and the other did not. In analyzing the data, we considered four commonly used dependent variables (post-test score, absolute change score, relative change score, residual score), five regression models, eight sample sizes, and four levels of reliability.Results Our results indicated that a regression model including the investigated predictor, Group (experimental vs. control), pre-test score, and the interaction between the investigated predictor and the Group as predictors, and the absolute change score as the dependent variable seemed most convenient for the given experimental design. Although the pre-test score should be included as a predictor in the regression model for reasons of statistical power, its coefficient should not be interpreted because even if there is no true relationship, a negative and statistically significant regression coefficient commonly emerges.Conclusion Employing simulation methods, theoretical reasoning, and mathematical derivations, we were able to derive recommendations regarding the analysis of data in one of the most prevalent experimental designs in research on CT and external predictors of CT success. These insights can contribute to the application of considered data analyses in future studies and facilitate cumulative knowledge gain.
Structural Insights Into the Design of Peptide-based Drug or Diagnostic Reagent Antagonizing SARS-COV-2
Authors: jiang junhao , Deng Ping 
Published: August 2020

Abstract
Background

Very limited drug and diagnostic reagents are currently available to tackle the emergence of SARS-CoV-2. However, recent findings about the structure of the complex about PD of ACE2 and RBD of SARS-CoV-2 spike protein hold great promise for the design of novel vaccines and peptides. To provide some suggestions for the design of peptide-based drug or diagnostic reagents antagonizing SARS-CoV-2, and describe the interactions between the receptor-binding domain of SARS-CoV-2 and PD domain of its receptor, ACE2.
Methods

Based on the PD-RBD crystal structure, the molecular interaction details of PD-RBD was contrasted.
Results

Amino acid mutations located in RBM of SARS-CoV result in the formation of new interactions between SARS-CoV-2 and α-helix 1, which can increase the binding affinity of SARS-CoV-2 to ACE2. It is confirmed that the α-helix 1 on ACE2 is the most important domain for binding spike glycoprotein of SARS-CoV-2, which can be used as a leading peptide for drug and diagnostic reagents development.
Conclusion

Based on the molecular-level characterization analysis between the PD and RBD, severe important amino acid residues (Q24, T27, K31, and H34) on α-helix 1 are proposed to mutate into increasing the binding affinity. Although the information provided in this study is predictive and based on no experimental evidence, it may provide useful suggestions for the experimental scientists to synthesize the proposed peptide and test their binding affinity and blocking capacity, and may be helpful for the understanding of SARS-CoV-2 entry.
Increased Frequency of β Cells with Abnormal NKX6.1 Expression in Type 2 Diabetes but not in Subjects with Higher Risk for Type 2 Diabetes
Authors: Liu Tengli , Sun Peng , Zou Jiaqi , Wang Le , Wang Guanqiao , Liu Na , Liu Yaojuan , Ding Xuejie , Zhang Boya , Liang Rui , Wang Shusen , Shen Zhongyang 
Published: August 2020

Abstract
Background: NKX6.1 is a transcription factor for insulin, as well as a marker for β cell maturity. Abnormal NKX6.1 expression in β cells, such as translocation from the nucleus to cytoplasm or lost expression, has been shown as a marker for β cell dedifferentiation.Methods: Here, we obtained pancreata sections from organ donors, and aim to characterize NKX6.1 expression in subjects with or without type 2 diabetes mellitus (T2DM), and NKX6.1 and insulin immunofluorescence staining was performed.Results: Our results showed that cells with insulin expression but no nucleic NKX6.1 expression (NKX6.1 Nuc- Ins + ), and cells with cytoplasmic NKX6.1 expression but no insulin expression (NKX6.1 cyt Ins - ) were significantly increased in T2DM subjects and positively correlated with glycated hemoglobin (HbA1c), indicating the elevated β cell dedifferentiation with NKX6.1 inactivation in T2DM. To investigate whether β cell dedifferentiation has initiated in subjects with higher risks for T2DM, we next analyzed the association between β-cell dedifferentiation level in ND subjects with different ages, body mass index, and HbA1c. The results showed the absolute number and percentage of dedifferentiated β cells with NKX6.1 inactivation did not significantly change in subjects with advanced aging, obesity, or modest hyperglycemia, indicating that the β cell dedifferentiation may mainly occur after T2DM was diagnosed.Conclusion: In sum, our results suggested that NKX6.1 expression in β cells is changed in type 2 diabetic subjects, evidenced by significantly increased NKX6.1 Nuc- Ins + and NKX6.1 cyt Ins - cells. This abnormality does not occur more frequently in subjects with a higher risk for T2DM, suggesting that β cell dedifferentiation might be secondary to the pathological changes in T2DM.
Experiences and Health-seeking Behaviour of Couples in Ekiti-State Nigeria towards Infertility
Authors: Esan Deborah Tolulope , Nnamani Kelechi Queedaline , Ogunkorode Agatha , Muhammad Fatimah , Oluwagbemi Olamide Oluyemisi 
Published: August 2020

Abstract
Background: Infertility has been described as the most important reproductive health concerns of Nigerian women. Based on the importance placed on offspring in the African context, infertility contributes to high level of psychological distress, conflicts between couples and subject those faced with the challenge to hazardous sexual behaviors. This study therefore explored the experiences and health-seeking behaviors of couples towards infertility.Methods: The study employed a qualitative research design. In-depth interviews were conducted with fifteen participants who had been diagnosed with primary or secondary infertility, who were currently receiving treatment at a tertiary health institution in the Ekiti State. Thematic categorization and content analysis was used to analyze the data. Results: Majority of the participant were Female (14 out of 15), between the ages of 20-35(80%) and are Christian (100%). All the participants reported negative emotional and psychological effects of infertility as they all expressed their unhappiness on the issue of infertility and claimed that the issue has affected them in all spheres of life (socially, marital relationship and psychologically). Two of the participants claimed that their husbands had abandon them because of their inability to conceive. Majority of the participants also claimed that there is social stigma associated with the condition as almost all (14 of 15) said the society is not doing anything to support women facing infertility issue. All the participants utilized medical treatments in combination with religious activities as a form of treatment. Conclusion: The society is not doing enough to support couples with infertility issue. Supports group should be created in the society where couples with similar challenge can come together to freely discuss and share their experiences as this could help in alleviating the psychological distress associated with infertility.