Miracle-dz/UniFAR-FTUs huggingface dataset:
Modernizing the Methods and Analytics Curricula for Health Science Doctoral Programs

This perspective provides a rationale for redesigning and a framework for expanding the graduate health science analytics and biomedical doctoral program curricula. It responds to digital revolution pressures, ubiquitous proliferation of big biomedical data, substantial recent advances in scientific technologies, and rapid progress in health analytics. Specifically, the paper presents a set of common prerequisites, a proposal for core computational and data analytic curriculum, and a list of expected outcome competencies for graduates of doctoral health science and biomedical programs. The manuscript emphasizes the necessity for coordinated efforts of all stakeholders, including trainees, educators, academic institutions, funding agencies, and policy makers. Concrete recommendations are presented of how to ensure graduates with terminal health science analytics and biomedical degrees are trained and able to continuously self-learn, effectively communicate across disciplines, and promote adaptation and change to counteract the relentless pace of automation and the law of diminishing returns.
miR-20a-5p/TGFBR2 Axis Affects Pro-inflammatory Macrophages and Aggravates Liver Fibrosis

Combined inhibition of programmed death-ligand 1 (PD-L1) and transforming growth factor-β (TGF-β) displayed additive anti-tumor response in a subgroup of cancer patients, highlighting the importance of understanding the multifaceted roles of TGF-β in immunity and fibrosis. In the present research, we show that TGF-β signaling pathway, controlled by miR-20a-5p and transforming growth factor-β receptor 2 (TGFBR2), alters the inflammation and fibrosis processes in liver. We performed integrated analysis of differently expressed miRNA (DEM) associated with liver fibrosis and screened miR-20a-5p out as a key regulator in inflammation-driven liver fibrosis. We subsequently conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the genes targeted by miR-20a-5p. And the result showed that 12 target genes were significantly enriched in TGF-β signaling pathway. Further study showed that miR-20a-5p was down-regulated and involved in inflammation during liver fibrosis in human and mouse samples, indicating that miR-20a-5p and inflammation are functionally linked during liver fibrosis progression. To uncover the underlying pro-inflammatory mechanism of miR-20a-5p in liver fibrosis, we selected and verified TGFBR2, which is a key functional receptor in TGF-β signaling pathway, as a direct target gene of miR-20a-5p. The downregulation of miR-20a-5p in liver fibrosis resulted in TGFBR2-activated TGF-β signaling pathway, followed by the activation of macrophage and extracellular matrix (ECM) production by hepatic stellate cell (HSC). Our results identify the miR-20a-5p/TGFBR2 axis as a key regulator of TGF-β signaling, and highlight the critical role of miR-20a-5p in the development of liver fibrosis.
Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer

Radiation therapy (RT) is responsible for at least 40% of cancer cures, however treatment resistance remains a clinical problem. There have been recent advances in understanding the molecular mechanisms of radiation-induced cell death. The type of cell death after radiation depends on a number of factors including cell type, radiation dose and quality, oxygen tension, TP53 status, DNA repair capacity, cell cycle phase at time of radiation exposure, and the microenvironment. Mitotic catastrophe (a pathway preceding cell death that happens in mitosis or as a consequence of aberrant mitotic progression) is the primary context of radiation-induced cell death in solid cancers, although in a small subset of cancers such as haematopoietic malignancies, radiation results in immediate interphase apoptosis, occurring within hours after exposure. There is intense therapeutic interest in using stereotactic ablative body radiotherapy (SABR), a precise, high-dose form of RT given in a small number of fractions, to prime the immune system for cancer cell killing, but the optimal radiation dose and fractionation remain unclear. Additionally, promising novel radiosensitisers targeting the cell cycle and DNA repair pathways are being trialled. In the context of the increasing use of SABR and such novel agents in the clinic, we provide an updated primer on the major types of radiation-induced cell death, focussing on their molecular mechanisms, factors affecting their initiation, and their implications on immunogenicity.
Bacillus subtilis RarA Acts as a Positive RecA Accessory Protein

Ubiquitous RarA AAA+ ATPases play crucial roles in the cellular response to blocked replication forks in pro- and eukaryotes. Here, we provide evidence that absence of RarA reduced the viability of ΔrecA, ΔrecO, and recF15 cells during unperturbed growth. The rarA gene was epistatic to recO and recF genes in response to H2O2- or MMS-induced DNA damage. Conversely, the inactivation of rarA partially suppressed the HR defect of mutants lacking end-resection (ΔaddAB, ΔrecJ, ΔrecQ, ΔrecS) or branch migration (ΔruvAB, ΔrecG, ΔradA) activity. RarA contributes to RecA thread formation, that are thought to be the active forms of RecA during homology search. The absence of RarA reduced RecA accumulation, and the formation of visible RecA threads in vivo upon DNA damage. When ΔrarA was combined with mutations in genuine RecA accessory genes, RecA accumulation was further reduced in ΔrarA ΔrecU and ΔrarA ΔrecX double mutant cells, and was blocked in ΔrarA recF15 cells. These results suggest that RarA contributes to the assembly of RecA nucleoprotein filaments onto single-stranded DNA, and possibly antagonizes RecA filament disassembly.
In the Wake of the Ongoing Mass Mortality Events: Co-occurrence of Mycobacterium, Haplosporidium and Other Pathogens in Pinna nobilis Collected in Italy and Spain (Mediterranean Sea)

Following the Mass Mortality Events (MMEs) of the pen shell P. nobilis in Campania region and Sicily, a survey of moribund P. nobilis specimens was also conducted in other Italian regions (Campania, Tuscany, Sardinia, and Apulia) and Spain (Catalunya). Histopathological and molecular examination of 27 specimens of P. nobils revealed different types of pathogens associated with tissue lesions, morbidity and mortality. Presence of Mycobacterium, Vibrio species, Haplosporidium pinnae and Perkinsus sp. were detected, differently distributed into the areas. The Mycobacterium sp. , previously reported in Campania and Sicily samples, was observed in all the analyzed areas and individuals, associated to systemic inflammatory lesions. In Spain, H. pinnae was observed in 36% of cases, always associated to the Mycobacterium sp. Molecular study using hsp65 genes and Internal Transcriber Spacer ITS support that a new species of Mycobacteria is infecting P. nobilis, close to M. triplex and belonging to the group of M. simiae complex with M. sherrisi. Presence of Perkinsus spp. resembling P. mediterraneus was observed in 2 out of 13 Italian individuals whose presence should be addressed as potential risk for shellfish aquaculture of the area. Vibrio spp. were also detected in some case. The preliminary results of this study suggest that Mycobacterium sp. , Vibrio spp. , H. pinnae and Perkinsus sp. cooperate to disease pathogenesis, being Mycobacterium and Haplosporidium most of the time involved. Vigilant inspection of those areas where MME is now starting, along with continuous systematic surveys, are crucial to define the spatiotemporal progress of mortality and the role of every single pathogen in the disease outcome.
Experiences of Recovery in EPAPSY’s Community Residential Facilities and the Five CHIME Concepts: A Qualitative Inquiry

In the context of the reform of psychiatric services in Greece, the debate about the concept of recovery is still growing. Recovery is defined as a path through which individuals facing mental health challenges are enabled to regain and further develop significant relationships with family, friends, the community, and themselves and at the same time to cope with the detrimental effects of stigma through empowerment. The present qualitative study aims to explore the experiences of people living in EPAPSY’s (Association for Regional Development and Mental Health) community residential facilities focusing mainly upon the key concepts of the CHIME (connectivity, hope, identity, meaning, and empowerment) conceptual framework of recovery. To this end, semi-structured interviews were conducted with seven participants living and receiving mental health care in a residential facility of EPAPSY. The participants’ accounts were analyzed using thematic analysis in a deductive and inductive manner. The research findings highlighted, among others, the challenges the participants faced during their early years in family and school, the experience of the revolving door effect, and the perceived turn their life took when they were transferred to a community residential facility, thus opening a new chapter in their lives. Of the five CHIME concepts, all are present in the participants’ accounts, with emphasis given to a meaningful present, a need to feel “normal” again, and a positive outlook for the future, both for themselves and their relationships, despite the persistence of certain difficulties.
Holistic Optimization of Bioinformatic Analysis Pipeline for Detection and Quantification of 2′-O-Methylations in RNA by RiboMethSeq

A major trend in the epitranscriptomics field over the last 5 years has been the high-throughput analysis of RNA modifications by a combination of specific chemical treatment(s), followed by library preparation and deep sequencing. Multiple protocols have been described for several important RNA modifications, such as 5-methylcytosine (m5C), pseudouridine (ψ), 1-methyladenosine (m1A), and 2′-O-methylation (Nm). One commonly used method is the alkaline cleavage-based RiboMethSeq protocol, where positions of reads' 5'-ends are used to distinguish nucleotides protected by ribose methylation. This method was successfully applied to detect and quantify Nm residues in various RNA species such as rRNA, tRNA, and snRNA. Such applications require adaptation of the initially published protocol(s), both at the wet bench and in the bioinformatics analysis. In this manuscript, we describe the optimization of RiboMethSeq bioinformatics at the level of initial read treatment, alignment to the reference sequence, counting the 5′- and 3′- ends, and calculation of the RiboMethSeq scores, allowing precise detection and quantification of the Nm-related signal. These improvements introduced in the original pipeline permit a more accurate detection of Nm candidates and a more precise quantification of Nm level variations. Applications of the improved RiboMethSeq treatment pipeline for different cellular RNA types are discussed.
Application of Twitter and web news mining in infectious disease surveillance systems and prospects for public health

Aims: With the advancements of communication technology and growing access to social networks, these networks now play an important role in the dissemination of information and news without going through the time-consuming channels of official news networks. Analysis of social networking data is a new, interesting branch of text mining science. This study aimed to develop a text mining technique for extracting information about infectious diseases from tweets and news on social media. Methods: A method called “Fuzzy Algorithm for Extraction, Monitoring, and Classification of Infectious Diseases” (FAEMC-ID) was developed by the use of fuzzy modeling of the Takagi-Sugeno-Kang type. In addition to the real-time classification, the method is able to update its vocabulary for new keywords and visualize the classified data on the world map to mark the high risk areas. Results: As an example, the monitoring was performed for measles-related news items over a 183-hour period from 01/03/2019 (01:00 am) to 08/03/2019 (12:00 pm), which were related to 2,870 tweets from 2,556 users. This monitoring showed that the number of tweets posted from each region ranged from 1 to 47, with the highest number, 47 tweets, belonging to Canada. The origins of most measles-related news were in the Americas and Europe, and they were mostly from the United States and Canada. Conclusion: The performance analysis of the developed method in comparison with other algorithms in the literature demonstrated the excellent precision of the method with a recall ratio of 88.41% and the high inter-correlation of data in each class. The proposed algorithm can also be used in the development of more effective monitoring and tracking systems for other human and even animal health hazards.
Long Noncoding RNA AFAP1-AS1 Promotes Cell Proliferation and Metastasis via the miR-155-5p/FGF7 Axis and Predicts Poor Prognosis in Gastric Cancer

Background Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) plays an important role in the development and progression of several human cancers. However, its biological function in gastric cancer (GC) progression is still unknown. Methods We used qRT-PCR to detect the relative expression of AFAP1-AS1 in GC tissues and cell lines. The loss-of-function assays were conducted to detect the effect of AFAP1-AS1 on GC development. Bioinformatics analysis, luciferase reporter gene analysis, and RIP analysis were used to identify and validate target genes of AFAP1-AS1. Finally, rescue tests were performed to confirm the influence of the AFAP1-AS1-miR-155-5p-FGF7 axis on GC development. Results AFAP1-AS1 was upregulated in GC tissues and cell lines and was closely correlated with poor prognosis of GC patients. AFAP1-AS1 knockdown inhibited proliferation, migration, and invasion of GC cells, indicating that AFAP1-AS1 acts as an oncogene in GC. Bioinformatics analysis, dual-luciferase reporter gene detection, and RIP assays validated that AFAP1-AS1 directly interacts to miR-155-5p and could positively affect cell proliferation, migration, and invasion by regulation of the expression of miR-155-5p and FGF7. Further rescue assays revealed that AFAP1-AS1 promotes cell proliferation and metastasis through the miR-155-5p/FGF7 axis in GC. Conclusions AFAP1-AS1 might be an oncogenic lncRNA that promoted GC progression by acting as a competing endogenous RNA (ceRNA) that regulates the expression of FGF7 through sponging miR-155-5p, suggesting that AFAP1-AS1 may be a novel potential therapeutic target for GC.
Effect of Stellaria media Tea on Lipid Profile in Rats

Background In folk medicine, common chickweed (Stellaria media) has traditionally been applied for the treatment of hypercholesterolemia; however, there is no firm experimental proof to support the rationale of this practice. Therefore, we aimed to assess the efficacy and safety of Stellaria media) has traditionally been applied for the treatment of hypercholesterolemia; however, there is no firm experimental proof to support the rationale of this practice. Therefore, we aimed to assess the efficacy and safety of Materials and Methods. Adult male Wistar rats were divided into 3 groups. The (i) control group received standard laboratory chow, the (ii) hypercholesterolemic group received cholesterol-enriched diet, and the (iii) chickweed-treated hypercholesterolemic group received cholesterol-enriched diet and 100 mg/kg body weight Stellaria media) has traditionally been applied for the treatment of hypercholesterolemia; however, there is no firm experimental proof to support the rationale of this practice. Therefore, we aimed to assess the efficacy and safety of Results Cholesterol-enriched diet significantly increased serum total cholesterol, LDL- and HDL-cholesterol levels, but did not affect triacylglycerol concentrations. The addition of chickweed to the diet did not cause any significant change in serum lipid profile or body weight increase. Liver and kidney functions were unaltered and cardiac morphology and function were not changed due to Stellaria media) has traditionally been applied for the treatment of hypercholesterolemia; however, there is no firm experimental proof to support the rationale of this practice. Therefore, we aimed to assess the efficacy and safety of Conclusion Although chickweed does not seem to be toxic, our results do not support the rationale of its use in the treatment of hypercholesterolemia.
Exosome-Mediated Transfer of ACE2 (Angiotensin-Converting Enzyme 2) from Endothelial Progenitor Cells Promotes Survival and Function of Endothelial Cell

Angiotensin-converting enzyme 2 (ACE2) is an emerging cardiovascular protective target that mediates the metabolism of angiotensin (Ang) II into Ang (1–7). Our group has demonstrated that ACE2 overexpression enhances the function of endothelial progenitor cells (EPCs). Here, we investigated whether ACE2-primed EPCs (ACE2-EPCs) can protect cerebral microvascular endothelial cells (ECs) against injury and dysfunction in an in vitro model, with focusing on their exosomal and cytokine paracrine effects on endothelial mitochondria. Human EPCs were transfected with lentivirus containing null or human ACE2 cDNA (denoted as Null-EPCs and ACE2-EPCs, respectively). Their conditioned culture media, w/wo depletion of exosomes (ACE2-EPC-CMEX-, Null-EPC-CMEX-, ACE2-EPC-CM, and Null-EPC-CM), were used for coculture experiments. EC injury and dysfunction model was induced by Ang II before coculture. Apoptosis, angiogenic ability, mitochondrion functions (ROS production, membrane potential, fragmentation), and gene expressions (ACE2, Nox2, and Nox4) of ECs were analyzed. The supernatant was collected for measuring the levels of ACE2, Ang II/Ang-(1–7), and growth factors (VEGF and IGF). Our results showed that (1) ACE2-EPC-CM had higher levels of ACE2, Ang (1–7), VEGF, and IGF than that of Null-EPC-CM. (2) Ang II-injured ECs displayed an increase of apoptotic rate and reduction in tube formation and migration abilities, which were associated with ACE2 downregulation, Ang II/Ang (1–7) imbalance, Nox2/Nox4 upregulation, ROS overproduction, an increase of mitochondrion fragmentation, and a decrease of membrane potential. (3) ACE2-EPC-CM had better protective effects than Null-EPC-CM on Ang II-injured ECs, which were associated with the improvements on ACE2 expression, Ang II/Ang (1–7) balance, and mitochondrial functions. (4) ACE2-EPC-CMEX- and Null-EPC-CMEX- showed reduced effects as compared to ACE2-EPCs-CM and Null-EPCs-CM. In conclusion, our data demonstrate that ACE2 overexpression can enhance the protective effects of EPCs on ECs injury, majorly through the exosomal effects on mitochondrial function.
Effectiveness and Safety of Acupuncture for Perimenopausal Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective To determine the effectiveness and safety of acupuncture for perimenopausal depression. Methods We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CNKI, VIP Citation Databases, Wan Fang, and online trial registries such as ClinicalTrials.gov for randomized controlled trials (RCTs) assessing the efficacy and safety of acupuncture for perimenopausal depression. Literature screening, data extraction, and determination of the risk of bias were performed by two researchers independently. The extracted data were pooled and meta-analyzed using RevMan5.3 software. Results In total, 16 RCTs covering 1311 patients were enrolled. Overall, the results showed that acupuncture was more effective in the treatment of perimenopausal depression than antidepressants (OR = 2.68, 95% CI (1.84, 3.90), P < 0.00001). Furthermore, HAMD scores in the manual acupuncture group and electroacupuncture group were lower than those of antidepressants (manual acupuncture vs. antidepressants (MD = −2.35, 95% CI (−2.93, −1.77), P < 0.00001) and electroacupuncture vs. antidepressants (MD = −1.2, 95% CI (−1.92, −0.48), P=0.001)). Data analysis revealed that the treatment effect of acupuncture was more stable than that of antidepressants (MD = −2.4, 95% CI (−3.37, −1.43), P < 0.00001). Moreover, acupuncture was safer than antidepressants based on the incidence of adverse events (OR = 0.23, 95% CI (0.1, 0.52), P=0.0004). But acupuncture has no effect on estrogen levels (P ≥ 0.05). Conclusions Acupuncture for perimenopausal depression is safe and effective. Moreover, it has more stable long-term effects than antidepressants and hormone replacement therapy (HRT). We recommend acupuncture as a clinical treatment of perimenopausal depression.
Relationship between meiotic behaviour and fertility in backcross-1 derivatives of the [(Gossypium hirsutum × G. thurberi)2 × G. longicalyx] trispecies hybrid

Abstract Wild cotton species are an important source of desirable genes for genetic improvement of cultivated cotton Gossypium hirsutum Linnaeus, 1763. For the success of such an improvement, chromosome pairings and recombinations in hybrids are fundamental. The wild African species G. longicalyx Hutchinson & Lee, 1958 could be used as donor of the desirable trait of fiber fineness. Twelve BC1 plants obtained from the backcrossing of [(G. hirsutum × G. thurberi Todaro, 1877)2 × G. longicalyx] (AhDhD1F1, 2n = 4x = 52) trispecies hybrid (HTL) by G. hirsutum (cv. C2) (AhAhDhDh, 2n = 4x = 52) were investigated for meiotic behaviour and plant fertility. Their chromosome associations varied as follows: (2.5 to 11.5) I + (17 to 22) II + (0.31 to 1.93) III + (0.09 to 1.93) IV + (0 to 0.07) V + (0 to 0.14) VI. Their pollen fertility ranged from 4.67 to 32.10 %. Only four BC1 plants produced a few seeds through self-pollination. The remaining BC1 were totally self-sterile and usually presented the highest number of univalents. All BC1 materials produced BC2 seeds (0.44 to 6.50 seeds per backcross) with the number of seeds negatively correlated with the number of univalents (R2 = 0.45, P < 0.05). Most BC1 plants gave significantly finer fiber compared to the cultivated G. hirsutum. SSR markers showed a segregation of wild alleles among the backcross derivatives and Genomic in situ hybridization (GISH) revealed presence of entire chromosomes of G. longicalyx as well as recombinant chromosomes in the backcross derivatives. The significance and details of these results are presented and the prospects of successfully exploiting these plant materials are discussed.
p16 promotes proliferation in cervical carcinoma cells through CDK6-HuR-IL1A axis

The Cyclin-Dependent Kinase Inhibitor p16 (p16) acts as a tumor suppressor in most cells, but for HPV transformed cervical cancer, in which oncoprotein E7 expressed by human papillomavirus (HPV) mediates the degradation of retinoblastoma protein (Rb), p16 exhibits oncogenic activity. Our study was conducted to study the mechanism underling p16 mediated promoting effect of cell proliferation in cervical cancer cell lines. CCK8 assay and EdU incorporation were conducted to evaluate cell proliferation. Loss-of-function assay was used to silence p16 in Ca Ski and SiHa cells. Next, western blot, qPCR, RNA silencing, luciferase activity assay, run-on assay, mRNA stability assay, RNA immunoprecipitation, co-immunoprecipitation Immunofluorescence were performed to examine the interaction between CDK6, HuR, and IL1A mRNA in p16 mediated proliferation promoting effect. Our results showed that: (1) Silencing p16 inhibited the proliferation of cervical cancer cells by decreasing the half-life of IL1A mRNA in CDK6 dependent manner; (2) The stabilization of IL1A mRNA was regulated by HuR which could be inactivated by p16/CDK6 mediated phosphorylation at Ser202; (3) IL1A mediated the oncogenic activity of p16 in cervical carcinoma cell lines. In conclusion, p16 promotes proliferation in cervical carcinoma cells through CDK6-HuR-IL1A axis.