Miracle-dz/UniFAR-FTUs huggingface dataset:
Attenuating nicotine’s effects with high affinity human anti-nicotine monoclonal antibodies

Use of nicotine-specific monoclonal antibodies (mAbs) to sequester and reduce nicotine distribution to brain has been proposed as a therapeutic approach to treat nicotine addiction (the basis of tobacco use disorder). A series of monoclonal antibodies with high affinity for nicotine (nic•mAbs) was isolated from B-cells of vaccinated smokers. Genes encoding 32 unique nicotine binding antibodies were cloned, and the mAbs expressed and tested by surface plasmon resonance to determine their affinity for S-(–)-nicotine. The highest affinity nic•mAbs had binding affinity constants (KD) between 5 and 67 nM. The 4 highest affinity nic•mAbs were selected to undergo additional secondary screening for antigen-specificity, protein properties (including aggregation and stability), and functional in vivo studies to evaluate their capacity for reducing nicotine distribution to brain in rats. The 2 most potent nic•mAbs in single-dose nicotine pharmacokinetic experiments were further tested in a dose-response in vivo study. The most potent lead, ATI-1013, was selected as the lead candidate based on the results of these studies. Pretreatment with 40 and 80 mg/kg ATI-1013 reduced brain nicotine levels by 56 and 95%, respectively, in a repeated nicotine dosing experiment simulating very heavy smoking. Nicotine self-administration was also significantly reduced in rats treated with ATI-1013. A pilot rat 30-day repeat-dose toxicology study (4x200mg/kg ATI-1013) in the presence of nicotine indicated no drug-related safety concerns. These data provide evidence that ATI-1013 could be a potential therapy for the treatment of nicotine addiction.
Quality Appraisal of the Pharmacoeconomic Research Literature about Antivirals: A Comparison between Chinese Medicine and Non-Chinese Medicine

Introduction Antiviral activity is a main function of many types of traditional Chinese medicine (TCM), and they may contribute more in the process of certain viral epidemics. Therefore, based on the effectiveness and economy of TCM, we aimed to determine the situation of health economic studies about antivirals, especially the difference between TCM and non-TCM. Methods A literature search of three databases was conducted with a time range of January 2000–December 2020, and terms related to health economics and TCM were used as key terms. QHES and CHEERS were used as quality assessment tools. Results 203 papers were included in our research. After evaluation using QHES and CHEERS, antiviral TCM obtained an overall score of 41.37 ± 4.46/99 in QHES, compared with 48.89 ± 7.25/99 (18.18% higher than TCM) of antiviral non-TCM. Conclusion With a statistically significant difference, the overall quality of pharmacoeconomic research about antiviral non-Chinese medicine is better than that about antiviral Chinese medicine, which may have resulted from researchers' capacities or the absence of a more suitable standard for pharmacoeconomic research. It tells that the quality of pharmacoeconomic studies about TCM still warrants improvement.
Full Genomic Sequences of H5N1 Highly Pathogenic Avian Influenza Virus in Human Autopsy Specimens Reveal Genetic Variability and Adaptive Changes for Growth in MDCK Cell Cultures

The entire H5N1 highly pathogenic avian influenza viral genomes were identified in the frozen autopsy specimens: the trachea, lung, colon, and intestinal feces from a patient who died of the disease in 2006. Phylogenetic analysis of the viral genomes showed that these viruses belonged to clade 1 and were the reassortants generated from the reassortment of the viruses within the same clade. The sequencing data from the autopsy specimens revealed at least 8 quasispecies of the H5N1 viruses across all 4 specimen types. These sequences were compared to those derived from the virus isolates grown in Madin Darby canine kidney (MDCK) cells. The virus isolates from the trachea, lung, and fecal specimens showed 27 nucleotide substitutions, leading to the changes of 18 amino acid residues. However, there was no change in the amino acid residues that determined the viral virulence. The changes were more commonly observed in the lung, particularly in the HA and NA genes. Our study suggested that the adaptation changes for the viral fitness to survive in a new host species (MDCK cells) might involve many genes, for example, the amino acid substitution 177G or 177W adjacent to the receptor-binding residues in the HA1 globular head and the substitution M315I in PB2. However, a mutation changes near the receptor binding domain may play an important role in determining the cell tropism and is needed to be further explored.
Assessing national cervical cancer screening guidelines: Results from an HIV testing clinic also screening for cervical cancer and HPV in Soweto, South Africa

Objective A screening centre in Soweto, South Africa (SA), investigated high-risk human papillomavirus (HR-HPV), HIV, cervical cancer risk amongst women. Methods This cross-sectional study (June 2018-March 2019) describes screening results (Roche Linear Array HPV test and Pap smear liquid based cytology) and history of screening (known HIV status, antiretroviral therapy [ART] use, previous Pap smears). Data were stratified by age group (18–29, 30+ years), HIV status, Pap smear results and tested for statistical significance. Results Of 280 women, 20.4% were HIV-positive, 18.2% had abnormal Pap smears, 41.8% had HR-HPV. Of older women, 48.2% (n = 78/162) had never had a Pap smear. Of younger women, 89.0% (n = 105/118) never had a Pap smear, but had significantly more low-grade squamous intraepithelial lesions (LSIL) and other HR-HPV infection than older women (12.7%[n = 15/118] vs 4.9%[n = 8/162], p = 0.0193; and 49.2%[n = 58/118] vs 29.0%[n = 47/162], p = 0.0006; respectively). HIV-positive women had more abnormal cytology results and infection with other HR-HPV types or co-infection with other HR-HPV type(s)/HPV-16 compared to HIV-negative women (35.1%[n = 20/57] vs 13.9%[n = 31/223], p = 0.0002; 56.1%[n = 32/57] vs 32.7%[n = 73/223], p = 0.001; and 12.3%[n = 7/57] vs 4.9%[n = 11/223], p = 0.044; respectively). Of 57 HIV-positive women, 45.6% (n = 26) already knew their HIV status; of which 69.2% were on ART and 34.6% never had a Pap smear. Conclusion South African women have high rates of HIV, Pap smear abnormalities and HR-HPV, with low cervical cancer screening coverage. SA cervical cancer screening policy excludes (undiagnosed) HIV-positive and HIV-negative women <30 years, both populations found to have high prevalence of HR-HPV. HPV-based primary screening from 25 years could improve outcomes.
The Relationship Between Vitamin D and Infections Including COVID-19: Any Hopes?

Abstract Vitamin D is proposed to have a potential role in the pathogenicity, clinical presentation, prognosis, complications, and treatment of several diseases. In addition to its well-known role in calcium metabolism, vitamin D regulates both innate and adaptive immunity, and subsequently modulates the antiviral and antibacterial inflammatory immune responses. In view of the emerging coronavirus disease 2019 (COVID-19) pandemic, searching for potential therapeutic and protective strategies is of urgent interest, and vitamin D is one of the promising agents in this field. In this review, we present data from literature that supports the promising role of vitamin D in treatment and/or prevention of several infections including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review summarizes vitamin D metabolism and its role in inflammation, thrombosis and immune regulation. It also reviews, in short, the role of vitamin D and the impact of its deficiency in several infections namely tuberculosis, influenza, human immunodeficiency virus (HIV), and SARS-CoV-2. Considering the roles of vitamin D on immune modulation, controlling of thrombosis, and attacking several microorganisms, the current review will elaborate on the association between these salient roles of vitamin D and the pathogenicity of various infectious agents including COVID-19. Consequently, the comprehensive finding of the current review shows a possible significant impact of vitamin D supplement as a hope in preventing, treating, and/or improving the progression of certain infections, specifically during the worldwide attempts to fight against the COVID-19 pandemic and minimize the severity of health complications encountered accordingly. In addition, avoiding a status of vitamin D deficiency to obtain its positive effects on the immune system and its protective mechanism during infections will be a general benefit overall.
Effect of Common Culinary Methods Practiced in Sri Lanka on the Nutrient Composition of Commonly Consumed Vegetables and Other Foods

In Sri Lankan traditional cooking, coconut and spices are incorporated to enhance the taste, flavor, and aroma. However, little attention has been given to assess the effect of these ingredients on the nutritional and chemical composition of the consumed food. The objective of this study was to ascertain the effect of traditional cooking methods on the chemical composition of vegetables, cereals and cereal-based foods, legumes, and selected nonvegetarian food varieties consumed in the daily diet. The results indicate that the addition of coconut milk (CM), coconut scraps, and coconut oil (CO) had a significant impact on the fat content of the prepared foods (p < 0.05). Cooking facilitated the incorporation of fat into food. According to the results, more percentage increases of fat content were observed in tempered string beans (97.51%) and cauliflower milk curry (96.6%). Data revealed that boiling helped to reduce the fat content in cereals and legumes. The cooked foods prepared using traditional recipes with CM, CO, or scraps have higher nutritional content than raw foods and have a significant nourishing potential that meets the daily energy requirements (p < 0.05). It can be concluded that the chemical composition of cooked food serves as a more realistic guideline in recommending dietary interventions in disease and weight management.
Patient delay and associated factors among tuberculosis patients in Gamo zone public health facilities, Southern Ethiopia: An institution-based cross-sectional study

Background Delayed tuberculosis diagnosis and treatment increase morbidity, mortality, expenditure, and transmission in the community. Early diagnosis and initiation of treatment are essential for effective TB control. Therefore, the main objective of this study was to assess the magnitude and factors associated with patient delay among tuberculosis patients in Gamo Zone, Southern Ethiopia. Methods A cross-sectional study was conducted in Gamo Zone, Southern Ethiopia from February to April 2019. Fifteen health facilities of the study area were selected randomly and 255 TB patients who were ≥18 years of age were included. Data were collected using a questionnaire through face-to-face interviews and analyzed using SPSS version 20.0. Patient delay was analyzed using the median as the cut-off value. Multivariable logistic regression analysis was fitted to identify factors associated with patient delay. A p-value of ≤ 0.05 with 95% CI was considered to declare a statistically significant association. Results The median (inter-quartile range) of the patient delay was 30 (15–60) days. About 56.9% of patients had prolonged patients’ delay. Patient whose first contact were informal provider (adjusted odds ratio [AOR]: 2.24; 95% confidence interval [CI] 1.29, 3.86), presenting with weight loss (AOR: 2.53; 95%CI: 1.35, 4.74) and fatigue (AOR: 2.38; 95%CI: 1.36, 4.17) and body mass index (BMI) categories of underweight (AOR: 1.74; 95%CI: 1.01, 3.00) were independently associated with increased odds of patient delay. However, having good knowledge about TB (AOR: 0.44; 95% CI: 0.26, 0.76) significantly reduce patients’ delay. Conclusion In this study, a significant proportion of patients experienced more than the acceptable level for the patient delay. Knowledge about TB, the first action to illness, presenting symptoms, and BMI status were identified factors associated with patient delay. Hence, raising public awareness, regular training, and re-training of private and public healthcare providers, involving informal providers, and maintenance of a high index of suspicion for tuberculosis in the vulnerable population could reduce long delays in the management of TB.
A Cross-Sectional Study of Labial Bone and Covering Soft Tissue in Maxillary Anterior Segment: A Dilemma in Orthodontics

Purposes The thickness of the buccal bone and its covering gingiva is pivotal in determining the prognosis of implant therapy as well as fixed orthodontic appliances, especially nonextraction treatments. The purpose of this study was to evaluate the buccal bone thickness and covering soft tissue in the maxillary anterior segment. Methods This study measured the hard tissue thickness at 2 and 5 mm more apical from the crest and at the root apical apex, as well as the distance from the CEJ to the alveolar crest, using 80 CBCT images divided into three age groups. In addition, the distance from free gingiva to alveolar crest and from free gingiva to CEJ was measured. The acquired data then was analyzed using an ANOVA, t-test, and Pearson correlation to investigate any associations or statistically significant differences between parameters. Results The highest mean soft tissue thickness at the 5 mm level was for central incisors and the least for canine. The highest mean thickness of soft tissue at the crest level and its 2 mm apical level was related to central incisors and the lowest mean thickness at these levels was related to canine. Analysis of hard tissue variables showed the lower thickness of hard tissue at higher ages compared to the young patients group, but the thickness of the soft tissue increases with age. Conclusion The highest mean thickness of the buccal hard tissue in the maxillary anterior segment was in lateral and central incisors. Also, the most prominent thickness of the labial soft tissue was in the central and lateral incisors at levels close to the crest.
Experiences of friendships of young people with first-episode psychosis: A qualitative study

Background First episode psychosis and reduced social networks have been found to go hand in hand, but specific mechanisms are unclear. The manifestation of symptoms and the effect of stigma are two possibilities discussed in the literature but the experiences and views of young people with psychosis have been neglected. Aims To explore experiences of friendships of young people with first-episode psychosis, focusing especially on any perceived changes in their friendships or approach to peer relationships as a result of the illness. Methods Fourteen participants were interviewed using a semi-structured interview guide, which explored participants’ views and experiences of their friendships during the acute phase of illness and in the path to recovery, the impact of friendships on illness experience and of illness on patterns of social contact, and the potential role of services in supporting people with their friendships. Interviews were transcribed verbatim and analysed thematically. Results Identified themes included the loss of social contacts because both young people developing psychosis withdrew and because friends withdrew as illness developed. Regarding recovery, a unique role was identified for friends and participants were often making conscious efforts to rebuild social networks. Mental health services were viewed as having a limited direct role in this. Conclusions Supporting the development of opportunities and skills needed for social relationships following an episode of psychosis may be a useful focus.
SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer

Background Almost all metastatic hormone-sensitive prostate cancers (mHSPC) will develop into metastatic castration-resistant prostate cancer (mCRPC) after androgen deprivation therapy (ADT). The expression level of squalene monooxygenase (SQLE) is increased in CRPC cells and regulates cholesterol metabolism. This study verified the biological function and mechanisms of SQLE in CRPC. Methods The expression of SQLE in human prostate cancer cells was overexpressed or silenced and its efficacy on cell survival was determined by the MTS test. Energy metabolism phenotype test was evaluated by XF real-time ATP rate assay, XF cell mitochondrial stress test, XF glycolysis stress test and XF mito fuel flex test. Cell migration and invasion were evaluated by colony formation assays and transwell assays; the expression of mRNA and protein was assessed by RT-qPCR and Western blot, respectively. Moreover, BALB/c nude mice model was performed to evaluate the lymph node metastasis. Results In our study, we found that the expression level of SQLE was significantly increased in bicalutamide-resistant-C4-2B cells compared to LNCaP cells. SQLE knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and reduced lymph node metastasis by inhibiting fatty acid oxidation in mitochondria. We also found that terbinafine, the specific inhibitor of SQLE, can enhance the sensitivity of prostate cancer cells to bicalutamide. Conclusion Our study revealed that SQLE is involved in the progression of castration resistance in CRPC through mediating metabolic reprogramming, presenting SQLE as a new target for the treatment of mCRPC.
Urban-rural disparities in institutional delivery among women in East Africa: A decomposition analysis

Background Though institutional delivery plays a significant role in maternal and child health, there is substantial evidence that the majority of rural women have lower health facility delivery than urban women. So, identifying the drivers of these disparities will help policy-makers and programmers with the reduction of maternal and child death. Methods The study used the data on a nationwide representative sample from the most recent rounds of the Demographic and Health Survey (DHS) of four East African countries. A Blinder-Oaxaca decomposition analysis and its extensions was conducted to see the urban-rural differences in institutional delivery into two components: one that is explained by residence difference in the level of the determinants (covariate effects), and the other components was explained by differences in the effect of the covariates on the outcome (coefficient effects). Results The findings showed that institutional delivery rates were 21.00% in Ethiopia, 62.61% in Kenya, 65.29% in Tanzania and 74.64% in Uganda. The urban-rural difference in institutional delivery was higher in the case of Ethiopia (61%), Kenya (32%) and Tanzania (30.3%), while the gap was relatively lower in the case of Uganda (19.2%). Findings of the Blinder-Oaxaca decomposition and its extension showed that the covariate effect was dominant in all study countries. The results were robust to the different decomposition weighting schemes. The frequency of antenatal care, wealth and parity inequality between urban and rural households explains most of the institutional delivery gap. Conclusions The urban-rural institutional delivery disparities were high in study countries. By identifying the underlying factors behind the urban-rural institutional birth disparities, the findings of this study help in designing effective intervention measures targeted at reducing residential inequalities and improving population health outcomes. Future interventions to encourage institutional deliveries to rural women of these countries should therefore emphasize increasing rural women’s income, access to health care facilities to increase the frequency of antenatal care utilization.
A Genome-Wide Association Study of Age-Related Hearing Impairment in Middle- and Old-Aged Chinese Twins

Background Age-related hearing impairment (ARHI) is considered an unpreventable disorder. We aimed to detect specific genetic variants that are potentially related to ARHI via genome-wide association study (GWAS). Methods A sample of 131 dizygotic twins was genotyped for single-nucleotide polymorphism- (SNP-) based GWAS. Gene-based test was performed using VEGAS2. Pathway enrichment analysis was conducted by PASCAL. Results The twins are with a median age of 49 years, of which 128 were females and 134 were males. rs6633657 was the only SNP that reached the genome-wide significance level for better ear hearing level (BEHL) at 2.0 kHz (P = 1.19 × 10−8). Totally, 9, 10, 42, 7, 17, and 5 SNPs were suggestive evidence level for (P < 1 × 10−5) BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and pure tone average (PTA), respectively. Several promising genetic regions in chromosomes (near the C20orf196, AQPEP, UBQLN3, OR51B5, OR51I2, OR52D1, GLTP, GIT2, and PARK2) nominally associated with ARHI were identified. Gene-based analysis revealed 165, 173, 77, 178, 170, and 145 genes nominally associated with BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and PTA, respectively (P < 0.05). For BEHLs at 0.5, 1.0, and 2.0 kHz, the main enriched pathways were phosphatidylinositol signaling system, regulation of ornithine decarboxylase, eukaryotic translation initiation factor (EIF) pathway, amine compound solute carrier (SLC) transporters, synthesis of phosphoinositides (PIPS) at the plasma membrane, and phosphatidylinositols (PI) metabolism. Conclusions The genetic variations reported herein are significantly involved in functional genes and regulatory domains that mediate ARHI pathogenesis. These findings provide clues for the further unraveling of the molecular physiology of hearing functions and identifying novel diagnostic biomarkers and therapeutic targets of ARHI.
The Prevalence and Association of Stress Urinary Incontinence, Core Muscle Endurance, and Low Back Pain among Married Women in Saudi Arabia: A Case-Control Study

Purpose There may be a strong association among stress urinary incontinence (SUI), low back pain (LBP), and core muscle endurance (CME) in married women. This study is aimed at evaluating the prevalence and clinical association between SUI, CME, and LBP among married women in Saudi Arabia. Methods The study was based on a case-control research design, conducted among 143 women with LBP (mean age, 32 ± 7.4 years) and 160 healthy women (mean age, 31.7 ± 6.7 years). SUI, CME, and functional disability were assessed using the international consultation on the Incontinence Questionnaire-Short Form (ICIQ-SF), prone plank test (PP), and Oswestry Disability Index for LBP-United Arab Emirates edition (ODI-UAE). Results The prevalence of SUI was found to be 60% in the LBP group while 20% in the control group. CME revealed a stronger negative correlation with SUI in the LBP group (rs = −0.75) than in the control group (rs = −0.63). Conclusions The prevalence of SUI was observed higher in women with LBP than healthy women. CME exhibited a stronger association with SUI than LBP among women with LBP compared to healthy women in Saudi Arabia. Therefore, the role of CME in SUI development or vice versa among married women with LBP may be subjected to further research.