Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Antipsychotic Effectiveness and Comparison of the Efficacy of Monotherapy and Polypharmacy in Schizophrenia: A 3-Years Follow-Up “Real World” Study in China

Background: Discontinuation of antipsychotic treatment is a common problem in patients with schizophrenia and could reduce the effectiveness of treatment. Time to discontinuation (TTD) is one of the indicators of compliance and may also be an effective indicator of medication efficacy. The aim of the study was to compare the clinical effectiveness of quetiapine, olanzapine, risperidone, and aripiprazole in the real-world treatment of schizophrenia with 3-years follow-up. Method: A multi-center, open, cohort, prospective, real-world study was conducted. 706 patients were analyzed without intervention in medication selection and use, followed up for 3 years. Kaplan-Meier survival curves were used to draw the treatment discontinuation rates (TDR) curves at each time point. Cox proportional hazard regression model was used to assess the relative risk of TTD of antipsychotics. Results: There was a significant difference among monotherapy groups in all-cause antipsychotic treatment discontinuation (p = 0.0057). Among the four medications, the TDR of risperidone was the highest. Compared with polypharmacy, except for aripiprazole, the TDR of other three monotherapy medications were lower than that of polypharmacy, and olanzapine was statistically different (p = 0.0325). The cox regression analysis showed that after correction of Hochberg with multiple tests, only olanzapine had a relative risk lower than risperidone (p < 0.0083). Conclusions: The findings indicated that risperidone monotherapy and polypharmacy had the highest TDR and the shortest TTD. Olanzapine monotherapy had a relative risk lower than risperidone and was superior to polypharmacy.
Use of Single Cell Transcriptomic Techniques to Study the Role of High-Risk Human Papillomavirus Infection in Cervical Cancer

High-risk human papillomavirus (hrHPV) infection has been associated with a higher probability of progression to cervical cancer. However, several extensive studies have reported that the presence of hrHPV can lead to a better prognosis, but the mechanism of how this occurs is unclear. In this study, microbiological analysis was used to identify HPV infection as a factor for the prognosis of patients with cervical squamous cell carcinoma (CSCC). Comparing the interactions of HPV+ and HPV- malignant cells with immune cells as well as the trajectory of malignant cells either with or without HPV, we found that most of the HPV+ cells are well differentiated while HPV- cells appear to be hypo-fractionated. Using transcriptomic and immunostaining data, we validated a set of unfavourable molecules in the HPV- CSCC cells, including KRT16, ITGB1, CXCR1, VEGFA, CRCT1 and TNFRSF10B/DR5. This study provides a basis for the development of a rational post-operative follow-up programme and the development of an appropriate treatment plan for patients with cervical cancer.
Combining Traditional and Molecular Techniques Supports the Discovery of a Novel Legionella Species During Environmental Surveillance in a Healthcare Facility

Legionella surveillance plays a significant role not only to prevent the risk of infection but also to study the ecology of isolates, their characteristics, and how their prevalence changes in the environment. The difficulty in Legionella isolation, identification, and typing results in a low notification rate; therefore, human infection is still underestimated. In addition, during Legionella surveillance, the special attention given to Legionella pneumophila leads to an underestimation of the prevalence and risk of infection for other species. This study describes the workflow performed during environmental Legionella surveillance that resulted in the isolation of two strains, named 8cVS16 and 9fVS26, associated with the genus Legionella. Traditional and novel approaches such as standard culture technique, MALDI-TOF MS, gene sequencing, and whole-genome sequencing (WGS) analysis were combined to demonstrate that isolates belong to a novel species. The strain characteristics, the differences between macrophage infectivity potential (mip), RNA polymerase β subunit (rpoB), and reference gene sequences, the average nucleotide identity (ANI) of 90.4%, and the DNA–DNA digital hybridization (dDDH) analysis of 43% demonstrate that these isolates belong to a new Legionella species. The finding suggests that, during the culture technique, special attention should be paid to the characteristics of the isolates that are less associated with the Legionella genus in order to investigate the differences found using more sensitive methods. The characterization of the two newly discovered isolates based on morphological, biochemical, and microscopic characteristics is currently underway and will be described in another future study.
Wildlife Trade for Belief-Based Use: Insights From Traditional Healers in South Africa

The use of animals and plants as traditional remedies for medical and magico-religious purposes has a long history of socio-cultural and economic importance in South Africa. Herein, we aim to characterize the social and economic value of wild animal species used in traditional, belief-based medicine within South Africa from traditional healers’ perspective and to explore healers’ knowledge of plant-based alternatives to wildlife-based derivatives for this type of trade. Through structured surveys with five traditional healers, we sought to gain insight into the range of wild animal species used, as well as the purpose, the perceived commercial value and the perceived availability of commonly used species. Particular focus was placed on exploring the socio-economic value of lions due to their prominence within the traditional medicine market, both in South Africa and internationally. Three of the respondents interviewed had been generating an income from traditional healing for between 30 and 50 years, and the overall monetary gain across all respondents was between ZAR 30,000 (1,800 USD) and 120,000 (7,200 USD) per annum. Our study confirms that a wide range of wild animal species are used in traditional healing practices in South Africa, for both medicinal and magico-religious purposes. The traditional healers we interviewed cited 20 common wild animals from a range of vertebrate classes including birds, reptiles, mammals, and one invertebrate. These included a number of species listed as threatened on the IUCN Red List of Threatened Species. Traditional healers cited 32 different uses for wild animal parts, as well as 19 alternative plant-based preparations. For lions specifically, four out of five practitioners listed lions among their top three profitable derivatives and three practitioners reported that lion had become the most rare or unavailable species in the last 5 years. Although our study is based on a limited number of interview participants, we believe that our findings provide valuable initial insights into the socio-economic drivers of traditional healing practices in South Africa, and that further research quantifying medicinal and belief-based use of wild animal ingredients and their plant-based alternatives could help to inform approaches to managing related pressures exerted on wild populations in South Africa in the future.
Recent Molecular Insights into Agonist-specific Binding to the Mu-Opioid Receptor

Opioid agonists produce their analgesic effects primarily by acting at the µ-opioid receptor (µOR). µOR agonists with different efficacies exert diverse molecular changes in the µOR which dictate the faith of the receptor’s signaling pathway and possibly it’s the degree of desensitization. Since the development of the active conformations of the µOR, growing data have been published in relation to ligand-specific changes in µOR activation. In this regard, this review summarizes recent data regarding the most studied opioid agonists in in silico µOR activation, including how these ligands are recognized by the µOR, how their binding signal is transmitted toward the intracellular parts of the µOR, and finally, what type of large-scale movements do these changes trigger in the µOR’s domains.
An Outlook on the Complexity of Protein Morphogenesis in Health and Disease

The study of the mechanisms whereby proteins achieve their native functionally competent conformation has been a key issue in molecular biosciences over the last 6 decades. Nevertheless, there are several debated issues and open problems concerning some aspects of this fundamental problem. By considering the emerging complexity of the so-called “native state,” we attempt hereby to propose a personal account on some of the key topics in the field, ranging from the relationships between misfolding and diseases to the significance of protein disorder. Finally, we briefly describe the recent and exciting advances in predicting protein structures from their amino acid sequence.
UV-B Protective and Antioxidant Activities of Protein Hydrolysate From Sea Cucumber (Holothuria scabra) Using Enzymatic Hydrolysis

Sea cucumber is rich in protein that can be used to prepare a potential derived bioactive peptide for antioxidant and protective effect against UV-B induced skin cell damage. This study aimed to optimize preparation of sea cucumber hydrolysate with both UV-B protective and antioxidant activities using three commercial enzymes using response surface methodology (RSM) with a face-centered central composite design (face- centered CCD). Hydrolysis time and concentration of enzyme effects on the degree of hydrolysis (DH), yield, antioxidant and UV-B protective activities of sea cucumber hydrolysates were determined. The optimum conditions for sea cucumber hydrolysis using papain (SCP), alcalase (SCA), or flavourzyme (SCF) were 3.6, 5.0, and 4.1% (w/w protein), respectively, and a hydrolysis time of 360 min. The resulting hydrolysates had a DH of 81-91%, yield of 13-14%, IC50 for DPPH radical scavenging activity of 0.3-4.1 mg/mL, FRAP of 0.5-0.6 mmol FeSO4/mL, and IC50 for ABTS radical scavenging activity of 1.3-1.6 mg/mL. The UV-B protective activity was reported as the HaCaT cell viability percentage after UV-B treatment. The SCP, SCA, and SCF hydrolysates showed 72.4, 74.5, and 71.3% cell viability, respectively. The concentration of hydrolysates with 80% survival of HaCaT cells was 0.21, 0.15 and 0.20 mg/mL for SCP, SCA and SCF, respectively. Thus, the SCP was selected for bioactive peptide isolation and characterization. The SCP contained hydrophilic and hydrophobic amino acids of 42.4 and 57.6%, respectively. The ultrafiltration and Sephadex G-25 gel filtration chromatography were done for peptide isolation from the SCP. Six potential peptides were identified using LC-MS/MS as Leu-Val-Asn-Glu-Leu-Thr-Glu-Phe-Ala-Gln (1163 Da), Leu-Val-Asn-Glu-Val-Thr-Glu-Phe-Ala-Gln (1149 Da), Phe-Val-Asp-Ser-Ser-Ala-Thr-Thr (826 Da), Phe-Asn-Asp-Leu-Gly-Ala-Trp (821 Da), Phe-Pro-Asp-Thr-Thr-Thr-Leu (793 Da), and Lys-Phe-Gly-Glu-Gly-Lys (664).
Coptidis Rhizoma Suppresses Metastatic Behavior by Inhibiting TGF-β-Mediated Epithelial-Mesenchymal Transition in 5-FU-Resistant HCT116 Cells

Colorectal cancer (CRC) is the second most lethal malignancy worldwide. The high mortality rate of CRC is largely due to cancer metastasis. Recently, suppressing epithelial-to-mesenchymal transition (EMT) has been considered a promising strategy for treating metastatic cancer, especially drug-resistant metastatic cancer. The present study aimed to evaluate the antimetastatic effect of Coptidis Rhizoma, as well as the potential underlying mechanisms, using a 5-fluorouracil-resistant colon tumor cell model (HCT116/R). Coptidis Rhizoma 30% ethanol extract (CRE) significantly inhibited HCT116/R cells migration and invasion. CRE effectively inhibited EMT in HCT116/R cells by upregulating the expression of an epithelial marker (E-cadherin) and downregulating the expression of mesenchymal markers (vimentin, Snail, and ZEB2) at both the protein and gene levels. Immunofluorescence assays also confirmed consistent patterns in the levels of E-cadherin and vimentin. In addition, the anti-EMT activity of CRE and its related effects were associated with the CRE-mediated suppression of the TGF-β pathway, as shown by changes in the levels of downstream molecules (phosphorylated Akt and p38), and inhibition of migration, invasion, and protein expression of TGF-β after treatment/cotreatment with a TGF-β inhibitor (SB431542). In conclusion, Coptidis Rhizoma exerts an antimetastatic effect, especially in the treatment of drug-resistant cancer, and the possible mechanisms are associated with inhibiting EMT via TGF-β signaling. Thus, Coptidis Rhizoma will likely become a potential therapeutic candidate for simultaneously mitigating drug resistance and metastasis in CRC.
Awareness, Knowledge, and Perceptions Regarding Rabies Prevention Among Rural Communities in Masaka District, Central Uganda: A Qualitative Study

Rabies is a zoonotic disease that is mainly transmitted to humans through dog bites. It remains a major public health threat in many Asian and African countries, including Uganda. The main objective of this study was to investigate awareness, knowledge, and perceptions of communities toward human and dog health related to rabies prevention, as well as dog management practices within Masaka district, central Uganda. Data collection involved nine key informant interviews (KIIs) and six focus group discussions (FGDs). Methods used during focus group discussions included qualitative interviews (using open-ended questions), simple ranking, and proportional piling. Data from KIIs and FGDs were analyzed using content analysis in NVivo (version 12.0). This study reveals that community members in the rural settings uses herbal concoctions in replacement or as an alternative to dog vaccination. Furthermore, the study reveals that dogs play the vital roles in the households like as they offer protection to people and household properties, despite being ranked second least among the household animals. The commonest livelihood activity was a small-scale mixed farming. Most of the households kept dogs, but they are ranked at second lowest in terms of economic value among all domestic animals. Free roaming and tethering were the common dog-keeping systems, and home-based feed (food leftovers, bones) was provided mainly to the tethered dogs. Rabies, also locally known as “Eddalu Lyembwa” (that can be translated as “madness of the dogs”), was ranked as the disease of most important among dogs, besides other common diseases such as skin diseases, venereal diseases, worm infestations, and tick infestations. Inadequate vaccination services for both humans and dogs were reported, and dog bite victims traveled a long distance to seek for post-exposure prophylaxis after dog bites. It can be concluded that there is a clear request for periodic mass vaccination campaigns against rabies among dogs, and access to vaccines within reasonable distances by humans after a rabies exposure, but also pre-emptive vaccination for those at high risk, such as veterinarians, needs to be improved.
Comparison of the Reproductive Outcome Between 2 and 4 mg Daily Doses of Estradiol After Hysteroscopic Adhesiolysis: A Propensity Score Matching Analysis–Retrospective Cohort Study

Objective To investigate the effect of two postoperative doses of estradiol valerate (2 and 4 mg/day) on reproductive outcomes in patients with moderate to severe intrauterine adhesions (IUAs). Methods A retrospective cohort study was conducted at a single tertiary reproductive medical center between January 2018 and December 2019 to compare the reproductive outcomes of two doses of estradiol valerate (2 and 4 mg daily) after hysteroscopic adhesiolysis. All patients received adjuvant postoperative treatment with a Foley catheter, hyaluronic acid gel, and medication therapy. Hysteroscopy was repeated every 7 days after surgery. Multivariate regression analysis and propensity score matching (PSM) were performed to minimize intrinsic bias. Results A total of 212 patients with moderate to severe IUAs were included: 74 patients received 2 mg of estradiol valerate daily and 138 patients received 4 mg of estradiol daily postoperatively. No significant differences were found in the reproductive outcomes between the two groups, including clinical pregnancy rates. The multivariable regression analyses both before and after PSM also showed that there was no significant difference in the menstrual improvement and clinical pregnancy rates between the two groups. Conclusions We suggest the use of a lower dose (2 mg/day) of estradiol valerate as an adjuvant therapy for IUAs to minimize estrogen-related side effects.
Clinical Observation of Extensively Hydrolysis Protein Formula With Feeding Intolerance in Preterm Infants

Objective To investigate whether feeding extensively hydrolysis protein formula during the NICU hospitalization was more beneficial for preterm infants with a gestational age (GA) ≤34 weeks when breastfeeding was not possible. Methods In total, 587 preterm infants were randomly divided into two groups: observation groups fed with extensively hydrolyzed formula (EHF) milk and control groups fed with standard preterm formula (SPF) milk until discharge from the neonatal intensive care unit (NICU). The incidence of complications during hospitalization was recorded in both groups. Then, two groups were uniformly fed with 0-to-6-month infant formula milk and followed-up for 6 months after discharge. Results The final study included 370 premature infants, including 185 babies in the observation group and 185 in the control group. In contrast to the SPF, feeding EHF among preterm infants of GA <34 weeks during NICU hospitalization significantly reduced the incidence of feeding intolerance (FI) (14.1 vs. 30.3%, p < 0.01). The incidence of necrotizing enterocolitis (NEC) was significantly reduced in the observation group (2.2 vs. 6.5%, p < 0.05), but there was no significant difference in the incidence of other related complications. At discharge, there was no difference in total serum protein (46.6 vs. 46.4 g/L), albumin (33.5 vs. 34.2 g/L), and calcium (2.37 vs. 2.35 mmol/L), but the serum phosphorus concentrations associated with skeletal mineralization (2.10 vs. 2.22 mmol/L, p < 0.05) was significantly reduced and alkaline phosphatase significantly rose (254 vs. 220 IU/L, p < 0.05) in the observation group. No significant difference was found in the growth rates of body weight, head circumference, or body length, either during the NICU hospitalization or during the 6-month follow-up after discharge (p > 0.05). Conclusions Feeding premature infants of GA ≤34 weeks with EHF reduced the incidence of FI, but had no advantage in establishing whole intestinal nutrition, shortening parenteral nutrition (PN) time, or hospitalization time. It had little effect on physical growth or development during NICU hospitalization and within 6 months after discharge. However, it may increase the incidence of metabolic bone disease (MBD).
The Need for Strengthening Health Information Dissemination Toward Indoor Residual Spraying for Malaria Prevention in Malarious Area of Ethiopia

Introduction Malaria remains prevalent in developing countries. This is particularly true among the community who are prone but do not apply malaria prevention and controlling strategies. In one of the malarious areas of Ethiopia (Shewa Robit), the acceptance level of indoor residual spraying (IRS) is indicated to be low as per guidelines. However, factors determining communities' acceptance of IRS are not well-investigated. Hence, this study was designed to identify the determinants for the acceptance of IRS in order to indicate priorities for malaria prevention and control. Methods A community-based cross-sectional study design was used among 649 households in Shewa Robit town, from February to March 2021. Households were selected from five IRS-targeted kebeles. Data were collected using structured questionnaire. A multivariable logistic regression model was used to identify the independent factors associated with the acceptance of IRS. Results The response rate in this study was 98%. The proportion of community who accepted the IRS for malaria prevention was 56.5% [95% confidence interval (CI): 52.7–60.2%]. Being male [adjusted odds ratio (AOR) = 2.21, 95% CI: 1.32–3.72], having good knowledge (AOR = 2.25, 95% CI: 1.33–3.84), did not paint/re-plaster the wall after spraying (AOR = 3.99, 95% CI: 2.36–6.76), did not perceive any side effects after spraying (AOR = 1.82, 95% CI: 1.11–2.99), effectiveness of previous IRS (AOR = 2.99, 95% CI: 1.85–4.84), non-utilization of long-lasting insecticide-treated net (LLIN) (AOR = 0.52, 95% CI: 0.33–0.84), and spraying the house at the right season (AOR: 2.14, 95% CI: 1.11–4.13) were determinant factors for the acceptance of IRS. Conclusions To increase the acceptance level of IRS among the communities, health interventions and services should focus on the awareness creation toward the effectiveness of IRS, proper spraying time/season, and side effects of IRS. Therefore, strengthening health information dissemination could help promote the acceptance of IRS.
Ecological Distribution and Diversity of Key Functional Genes for Denitrification in Surface Sediments of the Northern South China Sea: Implications for Potential N2O Emissions

Denitrification is an important pathway for nitrogen sink and N2O emissions, but little is known about the ecological distribution of key functional genes of denitrification and their potential N2O emissions in marine sediments. In this study, we analyzed the abundance, ecological distribution, and diversity of key functional genes (nir and nosZ) for denitrification in the northern South China Sea (SCS) surface sediments. Our results showed that the gene abundances varied from 105 to 108 and from 106 to 107 copies·g-1 for the nirS and nirK, respectively. The nosZ II/nosZ I gene abundance ratios were 1.28–9.88 in shallow-sea and deep-sea sediments, suggesting that the nosZ II gene should play a dominant role in N2O reduction in the northern SCS sediments. Moreover, the significantly higher abundance ratios of nir/nosZ in deep-sea surface sediments implied that there might be stronger N2O emissions potential in deep-sea sediments than in shallow-sea sediments. The ecological distribution profiles of the nirS, nosZ I, and nosZ II gene communities varied with water depth, and denitrification genes in shallow-sea and deep-sea sediments differed in their sensitivity to environmental factors. Water temperature was the major factor affecting both the abundance and the community distribution of the nirS gene in deep-sea sediments. Nitrate was the major factor shaping the community of nosZ I and nosZ II genes in shallow-sea sediments. Our study provides a pattern of ecological distribution and diversity for the nir and nosZ genes and emphasizes the role of these key functional genes in potential N2O emissions of the northern SCS surface sediments.