Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum Exosome-Derived miR-139-5p as a Potential Biomarker for Major Depressive Disorder

Background MicroRNAs (miRs) have been suggested to be biomarkers to inform the diagnosis of major depressive disorder (MDD). We have previously shown that exosome-derived miR-139-5p had potential in differentiating between patients with MDD and healthy control (HC) subjects. Materials and Methods To validate the potential of exosome-derived miR-139-5p as a biomarker for MDD, here we recruited 30 patients with MDD and 30 HC subjects, and used TaqMan probes to detect serum exosomal miR-139-5p levels. Results The data showed that patients with MDD had significantly increased exosomal miR-139-5p levels when compared with controls. Correlation analysis suggested that sex, age, and body mass index did not significantly affect blood exosomal miR-139-5p levels in the tested subjects. The ROC curve showed that serum-derived miR-139-5p had reasonable performance in discriminating patients with MDD and HC subjects, with a sensitivity of 0.867 and specificity of 0.767, and the AUC was 0.807. Discussion Taken together, these results demonstrated that patients with MDD were accompanied by significantly increased blood exosomal miR-139-5p levels, and exosomal miR-139-5p is a promising biomarker for the diagnosis of MDD.
An Integrating Immune-Related Signature to Improve Prognosis of Hepatocellular Carcinoma

Growing evidence suggests that the superiority of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) could act as biomarkers for cancer prognosis. However, the prognostic marker for hepatocellular carcinoma with high accuracy and sensitivity is still lacking. In this research, a retrospective, cohort-based study of genome-wide RNA-seq data of patients with hepatocellular carcinoma was carried out, and two protein-coding genes (GTPBP4, TREM-1) and one lncRNA (LINC00426) were sorted out to construct an integrative signature to predict the prognosis of patients. The results show that both the AUC and the C-index of this model perform well in TCGA validation dataset, cross-platform GEO validation dataset, and different subsets divided by gender, stage, and grade. The expression pattern and functional analysis show that all three genes contained in the model are associated with immune infiltration, cell proliferation, invasion, and metastasis, providing further confirmation of this model. In summary, the proposed model can effectively distinguish the high- and low-risk groups of hepatocellular carcinoma patients and is expected to shed light on the treatment of hepatocellular carcinoma and greatly improve the patients' prognosis.
Antimalarial Drug Resistance and Novel Targets for Antimalarial Drug Discovery

Abstract Malaria is among the most devastating and widespread tropical parasitic diseases in which most prevalent in developing countries. Antimalarial drug resistance is the ability of a parasite strain to survive and/or to multiply despite the administration and absorption of medicine given in doses equal to or higher than those usually recommended. Among the factors which facilitate the emergence of resistance to existing antimalarial drugs: the parasite mutation rate, the overall parasite load, the strength of drug selected, the treatment compliance, poor adherence to malaria treatment guideline, improper dosing, poor pharmacokinetic properties, fake drugs lead to inadequate drug exposure on parasites, and poor-quality antimalarial may aid and abet resistance. Malaria vaccines can be categorized into three categories: pre-erythrocytic, blood-stage, and transmission-blocking vaccines. Molecular markers of antimalarial drug resistance are used to screen for the emergence of resistance and assess its spread. It provides information about the parasite genetics associated with resistance, either single nucleotide polymorphisms or gene copy number variations which are associated with decreased susceptibility of parasites to antimalarial drugs. Glucose transporter PfHT1, kinases (Plasmodium kinome), food vacuole, apicoplast, cysteine proteases, and aminopeptidases are the novel targets for the development of new antimalarial drugs. Therefore, this review summarizes the antimalarial drug resistance and novel targets of antimalarial drugs.
Characteristics and Management of TP53-Mutated Diffuse Large B-Cell Lymphoma Patients

Background/Aim TP53 mutation is recognized as a negative prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). Here, we present the characteristics of TP53mut DLBCL patients following investigation of the effect of a treatment approach on survival of TP53mut DLBCL patients. Methods A total of 44 DLBCL patients with TP53mut and treated with an R-CHOP regimen were included for analysis. Patients who failed to achieve a complete response (CR) to initial treatment or relapsed in the first 6 months after initial CR were deemed to have primary refractory disease. Results Among 44 patients harboring TP53 mutations who underwent upfront R-CHOP or R-CHOP–like treatment, 21 (47.7%) had limited-stage and 23 (52.3%) presented advanced-stage disease. Apart from the seven patients receiving upfront surgical resection, 37 had measurable disease under the R-CHOP regimen, with 59.1% (n=26) developing primary refractory disease. Seven limited-stage patients after early complete resection and one with residue resection remained event-free at median follow-up of 37 months. Multivariate analysis revealed that elevated baseline lactate dehydrogenase (LDH), extranodal involvement (two or more), Ann Arbor stage, and locoregional treatment (surgery or radiation therapy) were independent indicators for progression-free survival (PFS). After adjustment for baseline LDH and extranodal involvement, adding locoregional treatment including surgery and radiation to the R-CHOP regimen significantly improved PFS (p=0.008) and overall survival (p=0.017) in limited-stage TP53mut DLBCL patients compared to R-CHOP–only treatment. Conclusion This study presents the characteristics of TP53-mutated DLBCL and implies a potential benefit of locoregional treatment in limited-stage DLBCL patients with TP53 mutations.
Prevalence and Factors Associated with Suicidal Ideation in Institutionalized Patients with Schizophrenia

Purpose The shorter life expectancy and increased risk of suicide in patients with schizophrenia have been well documented. However, study outcomes on suicidality in this special population have been few to date. This study investigated the prevalence and factors associated with suicidal ideation in a population of institutionalized patients with schizophrenia. Methods Two hundred fifty-six patients with schizophrenia between the age of 18 and 65 years were randomly recruited. This cross-sectional study utilised the Calgary Depression Scale for Schizophrenia (CDSS), the Positive and Negative Syndrome Scale (PANSS) and the Psychotic Symptom Rating Scale (PSYRATS-AH). Univariate analysis was performed using an independent t-test or chi-square test, followed by binary logistic regression to determine the factors associated with increased suicidal risks. Results The socio-demographic factors associated with suicidal ideation included level of education (p=0.039); secondary-level education (OR=5.76, 95% CI:1.49, 22.34, p=0.011) and tertiary-level education (OR=9.30, 95% CI: 1.80, 48.12, p=0.008) posed a greater risk. A history of attempted suicide (OR=2.09, 95% CI: 1.01, 4.36, p=0.049) and the presence of co-morbid physical illnesses (OR=2.07, 95% CI: 1.02, 4.21, p=0.044) were also found to be associated with a suicidal ideation. Other significant factors associated with suicidal thoughts were concurrent depression (OR=9.68, 95% CI: 3.74, 25.05, p<0.001) and a higher PSYRATS score in emotional characteristics of auditory hallucinations (OR=1.13, 95% CI: 1.06, 1.21, p<0.001). Conclusion Suicide in schizophrenia appears to be more closely associated with certain socio-demographic factors and affective symptoms. Appropriate screening and treatment addressing these challenges must be emphasized if suicidal thoughts and actions are to be reduced.
High Dosages of Equine Chorionic Gonadotropin Exert Adverse Effects on the Developmental Competence of IVF-Derived Mouse Embryos and Cause Oxidative Stress-Induced Aneuploidy

Gonadotropins play vital roles in the regulation of female reproductive ability and fertility. Our study aimed to determine the effects of superovulation induced by increasing doses of equine chorionic gonadotropin [eCG; also referred to as pregnant mare serum gonadotropin (PMSG)] on the developmental competence of mouse embryos and on aneuploidy formation during in vitro fertilization (IVF). eCG dose-dependently enhanced the oocyte yield from each mouse. Administration of 15 IU eCG significantly reduced the fertilization rate and the formation of four-cell embryos and blastocysts and increased the risk of chromosome aneuploidy. The IVF-derived blastocysts in the 15 IU eCG treatment group had the fewest total cells, inner cell mass (ICM) cells and trophectoderm (TE) cells. Moreover, more blastocysts and fewer apoptotic cells were observed in the 0, 5, and 10 IU eCG treatment groups than in the 15 IU eCG treatment group. We also investigated reactive oxygen species (ROS) levels and variations in several variables: mitochondrial membrane potential (MMP); active mitochondria; mitochondrial superoxide production; adenosine triphosphate (ATP) content; spindle structures; chromosome karyotypes; microfilament distribution; and the expression of Aurora B [an important component of the chromosomal passenger complex (CPC)], the spindle assembly checkpoint (SAC) protein mitotic arrest deficient 2 like 1 (MAD2L1), and the DNA damage response (DDR) protein γH2AX. Injection of 15 IU eCG increased ROS levels, rapidly reduced MMP, increased active mitochondria numbers and mitochondrial superoxide production, reduced ATP content, increased abnormal spindle formation rates, and induced abnormalities in chromosome number and microfilament distribution, suggesting that a high dose of eCG might alter developmental competence and exert negative effects on IVF-obtained mouse embryos. Additionally, the appearance of γH2AX and the significantly increased expression of Aurora B and MAD2L1 suggested that administration of relatively high doses of eCG caused Aurora B-mediated SAC activation triggered by ROS-induced DNA damage in early mouse IVF-derived embryos for self-correction of aneuploidy formation. These findings improve our understanding of the application of gonadotropins and provide a theoretical basis for gonadotropin treatment.
Progress in Stem Cell Therapy for Spinal Cord Injury

Background Spinal cord injury (SCI) is one of the serious neurological diseases that occur in young people with high morbidity and disability. However, there is still a lack of effective treatments for it. Stem cell (SC) treatment of SCI has gradually become a new research hotspot over the past decades. This article is aimed at reviewing the research progress of SC therapy for SCI. Methods Review the literature and summarize the effects, strategies, related mechanisms, safety, and clinical application of different SC types and new approaches in combination with SC in SCI treatment. Results A large number of studies have focused on SC therapy for SCI, most of which showed good effects. The common SC types for SCI treatment include mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), neural stem cells (NSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs). The modes of treatment include in vivo and in vitro induction. The pathways of transplantation consist of intravenous, transarterial, nasal, intraperitoneal, intrathecal, and intramedullary injections. Most of the SC treatments for SCI use a number of cells ranging from tens of thousands to millions. Early or late SC administration, application of immunosuppressant or not are still controversies. Potential mechanisms of SC therapy include tissue repair and replacement, neurotrophy, and regeneration and promotion of angiogenesis, antiapoptosis, and anti-inflammatory. Common safety issues include thrombosis and embolism, tumorigenicity and instability, infection, high fever, and even death. Recently, some new approaches, such as the pharmacological activation of endogenous SCs, biomaterials, 3D print, and optogenetics, have been also developed, which greatly improved the application of SC therapy for SCI. Conclusion Most studies support the effects of SC therapy on SCI, while a few studies do not. The cell types, mechanisms, and strategies of SC therapy for SCI are very different among studies. In addition, the safety cannot be ignored, and more clinical trials are required. The application of new technology will promote SC therapy of SCI.
Knowledge, Attitude, and Associated Factors towards Safe Abortion among Private College Female Students in Gondar City, Northwest Ethiopia: A Cross-Sectional Study

Background Women die from complications of unsafe abortion in developing countries because most have little knowledge about how to safely access to abortion care. Studies on knowledge, attitude, and associated factors towards safe abortion are limited in general and particularly among private college students. Therefore, the aim of this study was to assess knowledge, attitude, and associated factors towards safe abortion among private college female students in Gondar City, Northwest Ethiopia. Methods An institution-based cross-sectional study was conducted from April 30, 2019, to May 30, 2019, among private college students in the Gondar town. Data were collected from 633 female students using self-administered questionnaires by a simple random sampling technique. Bivariable and multivariable logistic regression analyses were performed to identify association of dependent and independent variables using SPSS, version 20. Results A total of 633 respondents participated in this study with the response rate of 97.7%. The majority (433 (68.4%)) of students had good knowledge about safe abortion. Older age (AOR = 2.79, 95% CI: 1.16, 7.29), urban residence (AOR = 2.42, 95% CI: 1.26, 4.35), family education (AOR = 3.18, 95% CI: 1.32, 7.06), and ever having heard about safe abortion (AOR = 4.36, 95% CI: 1.89, 10.83) were factors associated with knowledge of students on safe abortion. Regarding attitude, 361 (57%) of students had favorable attitude towards safe abortion. Age (AOR = 6.58, 95% CI: 2.71, 11.21) and urban residence (AOR = 1.51, 95% CI: 1.09, 2.21) were factors significantly associated with attitude towards safe abortion. Conclusion More than half of the participants have good knowledge and attitude towards safe abortion, but still a significant proportion of students have poor knowledge and unfavorable attitude. Information, education, and communication programs on youth reproductive health should be provided to address topics on safe abortion for students. Forums and panel discussions on safe abortion need to be undertaken especially, among youths and students who come from rural area.
Prescribing for Patients Seeking Maternal and Child Healthcare in Sierra Leone: A Multiregional Retrospective Cross-Sectional Assessments of Prescribing Pattern Using WHO Drug Use Indicators

Purpose Rational use of medicines is a necessary constrict towards increasing access for those that desperately need them in society. In this study, we assess medicines prescribing patterns in healthcare facilities implementing free healthcare policy for pregnant women, lactating mothers and children under the age of five in Sierra Leone. Materials and Methods Using WHO drug use indicators, we evaluated prescription records from the pharmacies of four hospitals; one from each of the four regions in Sierra Leone. To study prescribing indicators, we systematically sampled 1200 prescriptions overall (300/hospital) retrospectively spanning a year, from June 2017 to July 2018. In evaluating patients care indicators, we randomly sampled 120 (30/hospital) patients encounter prospectively. We used MS Excel 2016 and IMB SPSS in data analysis, and p< 0.05 was considered significant for associational analysis. Results The average drug per prescription was 3.6 (SD=1.3) overall, 3.5 (1.3) for children under five and 3.4 (1.4) for pregnant women/lactating mothers. Eighty-seven percent of prescriptions for under-five children contains antibiotics as opposed to 68.4% of prescriptions for pregnant women/lactating mothers. More injections were prescribed per encounter for pregnant women/lactating mothers 23.2% than for children under five 18.1%. Overall, generic prescribing and prescribing from the National Essential Medicines List were 74.9% and 73.8%, respectively. None of the studied health facilities dispensed all of the prescribed medicines. The most prescribed pharmacological class of drugs were antibiotics, and paracetamol was the most commonly prescribed drug. Conclusion Following WHO drug use indicators used in this study, drugs were irrationally prescribed within government hospitals providing free healthcare in Sierra Leone. Sustainability of the free healthcare scheme will require efficient medicine supply and management strategies. Therefore, the formulation of stewardship programs and/or an active Drug and Therapeutics Committee may be necessary to optimise drug use in these hospitals.
Acute Changes in Interleukin-6 Level During Four Days of Long-Distance Walking

Background Interleukin 6 (IL-6) has an inflammatory effect, and its concentration in serum increases during exercise. However, no studies have assessed acute changes in IL-6 concentration after consecutive days of extreme and long-term exercise. Objective This study aimed to assess acute changes in serum IL-6 concentration during four days of long-distance walking. Methods This prospective observational study assessed 25 athletes (aged 44.8 ± 9.1 years), who covered a total of 251 km in four days. Blood samples were collected daily to assess serum IL-6 concentrations. Repeated-measures analysis of variance (with Bonferroni’s post hoc test) and the Kruskal–Wallis H-test (with Dunn’s post hoc test) were used to investigate the differences between the measures. Results The serum IL-6 concentrations were higher on the four days of walking (1st day: 26.8 ± 14.8; 2nd day: 14 ± 7.4; 3rd day: 9.4 ± 10.8; 4th day: 4.5 ± 0.2 pg/mL) when compared to pre-walk values (pre-walk: 2.2 ± 2.1 pg/mL; p < 0.001). On the first day, there was a tenfold increase compared to the pre-walk value. Conclusion The inflammatory response increased the serum concentration of IL-6 after four days of exercise. With the passing of days, there were reductions but not to baseline values.
X-Linked Hypophosphatemia: A New Era in Management

Abstract X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive musculoskeletal disease that often causes pain and short stature, as well as decreased physical function, mobility, and quality of life. Hypophosphatemia in XLH is caused by loss of function mutations in the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene, resulting in excess levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23), which leads to renal phosphate wasting and decreased serum 1,25-dihydroxyvitamin D production. Historically, treatment options were limited to oral phosphate and active vitamin D analogues (conventional management) dosed several times daily in an attempt to improve skeletal mineralization by increasing serum phosphorus. The recent approval of burosumab, a fully human monoclonal antibody to FGF23, has provided a new, targeted treatment option for patients with XLH. This review summarizes our current understanding of XLH, the safety and efficacy of conventional management and burosumab, existing recommendations for managing patients, and unanswered questions in the field.
Identification of Genomic Alterations of Perineural Invasion in Patients with Stage II Colorectal Cancer

Purpose The molecular mechanism of perineural invasion (PNI) in stage II colorectal cancer (CRC) remains not to be defined clearly. This study aims to identify the genomic aberrations related to PNI in stage II CRC. Patients and Methods Using array-based comparative genomic hybridization (array-CGH), primary tumor tissues and paracancerous normal tissues of stage II CRC with PNI and without PNI were analyzed. We identified genomic aberrations by using Genomic Workbench and MD-SeeGH and validated the aberrations of selected genes by real-time polymerase chain reaction (PCR). Gene ontology (GO) and pathway analysis were performed to determine the most likely biological effects of these genes. Results The most frequent gains in stage II CRC were at 7q11.21-q11.22, 8p11.21, 8p12-p11.23, 8q11.1-q11.22, 13q12.13-q12.2, and 20q11.21-q11.23 and the most frequent losses were at 17p13.1-p12, 8p23.2, and 118q11.2-q23. Four high-level amplifications at 8p11.23-p11.22, 18q21.1, 19q11-q12, and 20q11.21-q13.32 and homozygous deletions at 20p12.1 were discovered in Stage II CRC. Gains at 7q11.21-q22.1, 16p11.2, 17q23.3-q25.3, 19p13.3-p12, and 20p13-p11.1, and losses at 11q11-q12.1, 11p15.5-p15.1, 18p11.21, and 18q21.1-q23 were more commonly found in patients with PNI by frequency plot comparison together with detailed genomic analysis. It is also observed that gains at 8q11.1-q24.3, 9q13-q34.3, and 13q12.3-q13.1, and losses at 8p23.3-p12, 17p13.3-p11.2, and 21q22.12 occurred more frequently in patients without PNI. Further validation showed that the expression of FLT1, FBXW7, FGFR1, SLC20A2 and SERPINI1 was significantly up-regulated in the NPNI group compared to the PNI group. GO and pathway analysis revealed some genes enriched in specific pathways. Conclusion These involved genomic changes in the PNI of stage II CRC may be useful to reveal the mechanisms underlying PNI and provide candidate biomarkers.
A Metagenomic Analysis of Mosquito Virome Collected From Different Animal Farms at Yunnan–Myanmar Border of China

Metagenomic analysis of mosquito-borne and mosquito-specific viruses is useful to understand the viral diversity and for the surveillance of pathogens of medical and veterinary importance. Yunnan province is located at the southwest of China and has rich abundance of mosquitoes. Arbovirus surveillance is not conducted regularly in this province particularly at animal farms, which have public health as well as veterinary importance. Here, we have analyzed 10 pools of mosquitoes belonging to Culex tritaeniorhyncus, Aedes aegypti, Anopheles sinensis, and Armigeres subalbatus species, collected from different animal farms located at Yunnan province of China by using metagenomic next-generation sequencing technique. The generated viral metagenomic data reveal that the viral community matched by the reads was highly diverse and varied in abundance among animal farms, which contained more than 19 viral taxonomic families, specific to vertebrates, invertebrates, fungi, plants, protozoa, and bacteria. Additionally, a large number of viral reads were related to viruses that are non-classified. The viral reads related to animal viruses included parvoviruses, anelloviruses, circoviruses, flaviviruses, rhabdoviruses, and seadornaviruses, which might be taken by mosquitoes from viremic animal hosts during blood feeding. Notably, the presence of viral reads matched with Japanese encephalitis virus, Getah virus, and porcine parvoviruses in mosquitoes collected from different geographic sites suggested a potential circulation of these viruses in their vertebrate hosts. Overall, this study provides a comprehensive knowledge of diverse viral populations present at animal farms of Yunnan province of China, which might be a potential source of diseases for humans and domestic animals.