Miracle-dz/UniFAR-FTUs huggingface dataset:
TRPML Cation Channels in Inflammation and Immunity

Background: In 1883, Ilya Mechnikov discovered phagocytes and established the concept of phagocytosis by macrophages. In 1908, he was awarded the Nobel Prize in Physiology/Medicine for his findings, which laid the foundations for today's understanding of the innate immune response. Only in the 1960s, Max Cooper and Robert Good significantly advanced our understanding of the immune system by demonstrating that B- and T-cells cooperate to regulate the adaptive immune response. Both, innate and adaptive immune response are essential to effectively protect the individual against infectious agents, such as viruses, bacterial or insect toxins, or allergens. Innate immune responses occur rapidly upon exposure to noxious or infectious agents or organisms, in contrast to the adaptive immune system that needs days rather than hours to develop and acts primarily on the basis of antigen-specific receptors expressed on the surface of B- and T-lymphocytes. In recent years, it has become evident that endosomes and lysosomes are involved in many aspects of immune cell function, such as phagocytosis, antigen presentation and processing by antigen-presenting cells, release of proinflammatory mediators, e.g., by mast cells, or secretion of the pore-forming protein perforin by cytotoxic T lymphocytes. Several lysosomal storage disorders (LSDs) have been associated with defects in immune system function or immune system hyperactivity, such as Gaucher, Fabry, or Niemann-Pick type C1 disease, mucopolysaccharidoses (MPS), gangliosidosis, or juvenile neuronal ceroid lipofuscinosis (JNCL). Beside accumulating evidence on the importance of endolysosomes in immune cell function, recent results suggest direct roles of endolysosomal ion channels, such as the TRPML channels (mucolipins), which are members of the transient receptor potential (TRP) superfamily of non-selective cation channels, for different aspects of immune cell function. The aim of this review is to discuss the current knowledge about the roles of TRPML channels in inflammation and immunity, and to assess their potential as drug targets to influence immune cell functions. Advances: Examples of recently established roles of TRPML channels in immune system function and immune response include the TRPML1-mediated modulation of secretory lysosomes, granzyme B content, and tuning of effector function in NK cells, TRPML1-dependent directional dendritic cell (DC) migration and DC chemotaxis, and the role of TRPML2 in chemokine release from LPS-stimulated macrophages. Outlook: Although our understanding of the functional roles of TRPML channels in inflammation and immunity is still in its infancy, a few interesting findings have been made in the past years, encouraging further and more detailed work on the role of TRPMLs, e.g., in intracellular trafficking and release of chemokines, cytokines, or granzyme B, or in phagocytosis and bacterial toxin and virus trafficking through the endolysosomal machinery.
Complications and limitations of endoscopic spine surgery and percutaneous instrumentation

Endoscopic spine surgery has started replacing conventional microdiscectomy in various centers across the globe. With development in the field of optics and instrumentation, the field of percutaneous endoscopic spine surgery has evolved immensely. With increasing experience, endoscopic spine surgeons have expanded the indications not only to lumbar paramedian disc herniations but also to central disc herniations, high-grade migrated disc herniations, sequestered herniations, thoracic and cervical disc herniations, and more recently, lumbar canal stenosis. With broadening indications, unexpected adverse events are bound to increase. Hence, it is essential for the endoscopic spine surgeons to be aware of the potential hazards and unexpected complications of the procedure so that appropriate care is taken to avoid adverse events as much as possible. In this article, we summarize all the complications of transforaminal endoscopic discectomy reported in the literature. We have classified the complications into intraoperative, immediate postoperative, and late postoperative complications. The senior author has also suggested the tips to avoid these complications and carry out the procedure as safely as possible. As percutaneous instrumentation, particularly, percutaneous pedicular screws, is also becoming common with the development of minimally invasive spine surgery, we have also summarized its complications and limitations. An insight into these complications will help the endoscopic surgeons to take special precautions when performing the procedure.
Supermarkets and Household Food Acquisition Patterns in Vietnam in Relation to Population Demographics and Socioeconomic Strata: Insights From Public Data

Food environments in Southeast Asia's emerging economies are rapidly evolving, alongside fast-paced socioeconomic and demographic changes. The widespread expansion of supermarkets and parallel restructuring of traditional markets in Vietnam are likely to impact patterns of household food acquisition. Using provincial-level time series data on the abundance of supermarkets and multiyear household survey data, this paper examines the impact of the differential country-wide presence of supermarkets with indices of food quality and quantity acquired by households. We classified provinces into three clusters based on the number of supermarkets: high (HighSM), medium (MedSM), and low (LowSM). We found that a higher number of supermarkets associated with the exceedable Vietnamese recommendation composition of macronutrients at the household-level, but not food quantity. Households with higher per capita food expenditure in HighSM provinces tended to procure foods with higher protein content and lower shares of fat and carbohydrate as compared to similar households in the others provinces. Ethnic minority households in MedSM clusters obtained food with lower carbohydrate and higher fat:protein ratios in comparison to ethnic majority households. Additionally, larger-sized households in HighSM provinces typically bought foods with higher fat shares than smaller-sized households. In contrast, in MedSM and LowSM provinces, larger-sized households typically procured foods with higher protein and lower fat shares. The diversity of foods obtained by households in MedSM and LowSM provinces decreased over time. Within the Midlands and Northern Mountains Area we observed a decrease in the diversity of food acquired among households in the LowSM clusters. This study elucidates potential impacts of the supermarket expansion on household food baskets. Insights from this study can be used to provide evidences for policy recommendation and to design and target interventions aimed at strengthening food environments to address the challenge of the double burden of malnutrition in the country.
miR-125a Induces HER2 Expression and Sensitivity to Trastuzumab in Triple-Negative Breast Cancer Lines

The EGFR/HER2 signaling network is an effective therapeutic target for HER2-positive cancers, which are known for their aggressive biological course. Evidence indicates that the EGFR/HER2 network plays a role in the aggressive basal-like subtype as well. Here, we studied the potential role of miR-125a-3p as a modulator of the EGFR/HER2 pathway in basal-like breast cancer. Over-expression of miR-125a-3p reduced the migratory capability of MDA-MB-231 cells and led to an increase in the expression of ErbB2 transcript and protein. The induced ErbB2 responded to trastuzumab and underwent internalization and subsequent intra-lysosomal degradation. Trastuzumab treatment further reduced the migratory capability and induced the apoptosis of the cells. An in-vivo mouse model, which supported the in-vitro findings, showed a synergistic effect for miR-125a-3p and trastuzumab. Trastuzumab-treated miR-125a-3p-induced tumors were significantly smaller than control induced tumors. Our findings indicate that, in the basal-like subtype of breast cancer, miR-125a-3p may act as a tumor suppressor. miR-125a-3p induces an increase in the expression of ErbB2 that may render the cells suitable for treatment with anti-HER2 therapies.
Prevalence, Incidence, Influence Factors, and Cognitive Characteristics of Amnestic Mild Cognitive Impairment Among Older Adult: A 1-Year Follow-Up Study in China

Background The risk and protective factors of amnestic mild cognitive impairment (aMCI) and its prevalence as well as incidence among old adult in Chinese community are still unclear. Methods We carried out this 1-year longitudinal study to survey a random sample of 3,246 community elders aged 60 and over in China. All subjects were required to complete a comprehensive clinical assessment, physical examination and several neuropsychological tests at baseline and follow-up. What’s more, we also collected their lifestyle information by a standardized questionnaire. Results We found that the prevalence of aMCI was 17.1%, while the incidence of aMCI among Chinese old adult was 70.57 per 1,000 person-years. By using Cox regression analysis, we found that male sex (p = 0.001, OR = 0.489, 95%CI 0.319~0.751) and reading (p = 0.023, OR = 0.533, 95%CI 0.310~0.917) were protective factors for against aMCI. Old adult who developed aMCI in the future showed multiple cognitive impairments (such as immediate memory, associative learning memory and executive function) in their early stage, and Wechsler’s Block Design (p = 0.027, OR = 0.969, 95%CL 0.943~0.996) could predict whether subjects would turn into aMCI in the future. Conclusions The present study suggests that aMCI is a considerable health problem in China. Executive dysfunction may be an indicator of future development of aMCI in the old normal adult.
The Role of Prognostic Factors in Salivary Gland Tumors Treated by Surgery and Adjuvant Radio- or Chemoradiotherapy – A Single Institution Experience

Purpose Salivary gland neoplasms are rare cancers of the head and neck region. Radical treatment in tumors of large salivary glands is surgery. Adjuvant treatment depends on the presence of risk factors that worsen the prognosis, but the role of these factors in patients treated by surgery with radio- or radiochemotherapy still remains unclear. The aim of the study is assessment of treatment results and identification of the risk factors affecting the prognosis in patients with tumors of large salivary glands subjected to adjuvant radio- or radiochemotherapy. Patients and Methods The study included 126 patients with local stage large salivary gland cancer who were treated surgically with adjuvant radio- or radiochemotherapy. The study excluded inoperable patients, patients with distant metastases, patients in a poor general condition and patients with contraindications to adjuvant treatment. They were treated between 2006 and 2016 and evaluated in terms of OS (overall survival), CSS (cancer-specific survival), RFS (relapse-free survival) and LRFS (local relapse-free survival). Results During a 44-month follow-up, 5-OS, CSS, RFS and LRFS were 55%, 68%, 60% and 73%, respectively. Multivariate analysis showed that OS was influenced by the following parameters: WHO performance status, TNM stage (T and N parameters), radicality of surgery, histopathological type, applied method of radiotherapy planning and tumor volume. WHO performance status, T and N parameters of the TNM stage and large volume of elective area influenced CSS, and the T parameter of the TNM stage, the dose below 60Gy and tumor volume influenced RFS and LRFS. Chemoradiotherapy can be used in N-positive patients. Conclusion The analysis indicates that the TNM grade, histopathological type, patient’s condition, radicality of the procedure, technique and dose of radiotherapy are the most important prognostic factors in these patients.
Analysis of Student Perceptions of Just-In-Time Teaching Pedagogy in PharmD Microbiology and Immunology Courses

Just-In-Time Teaching (JiTT) active learning pedagogy is utilized by various disciplines, but its value in a professional pharmacy curriculum has not yet been demonstrated. The purpose of our research study is to implement and evaluate JiTT in a Doctor of Pharmacy (PharmD) program. The impetus in implementing JiTT into a PharmD curriculum was to provide students with an out-of-classroom learning opportunity to enhance knowledge-based skills. The current study summarizes the implementation of JiTT in four distinct instances: two iterations of the required courses “Integrated Microbiology and Virology” (Fall 2016 and Fall 2017) and “Integrated Immunology” (Winter 2016–2017 and Winter 2017–2018). JiTT included knowledge-based questions in multiple-choice format, integrated case studies, and student responses prior to the actual lecture session. After the conclusion of each course, students were asked to provide feedback on the utilization of JiTT by way of an anonymous survey. Following the Fall 2016 iteration of the Microbiology & Virology course, students found the integrated case studies to be beneficial (mean = 3.27 out of a maximum of 4, SD = 0.62), and their overall endorsement of JiTT was high (mean = 3.61 out of 4, SD = 0.50). For the other three courses included in this study, the primary dependent variable was the student's average rating of JiTT, rated on a five-point scale. Aggregating the scores from the Fall 2017 iteration of the Integrated Microbiology & Virology course and both instances of the Immunology course, students rated JiTT very favorably (mean = 4.17 out of a maximum of 5, SD = 0.77). Students' performances in JiTT-based courses were compared against non-JiTT-based courses. Analysis of assessment data for student's performance on knowledge-based questions showed JiTT was helpful for student learning and JiTT-based courses had more consistent exam scores compared to non-JiTT-based courses. The current results are a promising initial step in validating the usefulness of JiTT in a pharmacy program and lays the foundation for future studies aimed at a direct comparison between a traditional lecture style and JiTT pedagogy implemented into PharmD curricula.
Introgression Among Cultivated and Wild Grapevine in Tuscany

Wild grapevine, Vitis vinifera L. subsp. sylvestris (Gmelin, Hegi) is spontaneous to Europe and common in Tuscany. In this study, wild grapevines were identified in 22 populations from eight locations in Tuscan Maremma (Grosseto and Siena province). The plants were propagated by cuttings, collected in a vineyard, genotyped by nuclear simple sequence repeats (SSRs), chloroplast SSRs and single nucleotide polymorphisms (SNPs), and compared to locally cultivated varieties (Vitis vinifera L. subsp. sativa) and to non-vinifera and non-vitis genotypes. The identity analysis revealed that some individuals were redundant genotypes, suggesting natural vegetative propagation. In addition, four of the supposed V.v. sylvestris were in fact naturalized V.v. sativa. The majority of putative sylvestris genotypes had chlorotype A, while the remainder had chlorotype D, as the majority of Vitis vinifera subsp. sativa cultivated in Italy. Some of the recovered sylvestris genotypes appeared to be natural crosses with cultivated grapevine varieties in Tuscany, and their chlorotype suggests a higher pollen flow from sativa to the sylvestris genotypes than in the opposite direction. In addition, other genotypes appeared to be crosses within sylvestris, sylvestris-sativa or sylvestris-sylvestris siblings, or equivalent relationships. These relationships suggest a noticeably level of sexual reproductive activities among sylvestris and sylvestris-sativa genotypes. A cluster and structure analysis clearly differentiated the true sylvestris from the sativa, and the non-vinifera or non-vitis genotypes, and also highlighted a possible introgression of sylvestris into some Italian and French cultivated varieties. The results therefore suggest that, in addition to the primary ancient center of domestication from the Near East to Central Asia, the introgression among cultivated and wild grapevine occurred in other centers of diversification along the migration routes, contributing to the domestication processes, and suggesting that these processes are still ongoing despite the reduction in populations of sylvestris. The results also highlight that the GrapeReSeq 18K Vitis genotyping chip are suitable for non-vitis genotyping and that the range of SNPs heterozygosity in sylvestris appears to be up to 6% less and does not overlap the heterozygosity range of sativa genotypes.
Education Moderates the Association of Probable REM Sleep Behavior Disorder With Cognitive and Motor Impairments in Community-Dwelling Older People

Objectives: To investigate the relationship between probable rapid eye movement (REM) sleep behavior disorder (pRBD) and cognitive/motor impairments in a community-dwelling population and explore the moderating effects of education. Methods: In this cross-sectional study of the Beijing Longitudinal Study of Aging II (BLSA II), 4,477 subjects (≥55 years) fulfilled the inclusion criteria. pRBD was determined by the RBD Questionnaire–Hong Kong (RBDQ-HK). Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to test the global cognitive performance. Walking speed was used to measure motor function. Logistic regression was performed to assess the relationship between pRBD and cognitive/motor impairments and the moderating effects of education. Results: There were 147 participants (3.3%) with pRBD. Participants with pRBD showed increased risks for cognitive impairment [odds ratio (OR) = 1.88, 95% CI 1.24–2.85, p = 0.003], decreased gait speed (OR = 1.43, 95% CI 1.02–2.01, p = 0.03), but not for mild cognitive impairment (MCI) (measured by MoCA: OR = 1.01, 95% CI 0.68–1.50, p = 0.95; measured by MMSE: OR = 0.90, 95% CI 0.59–1.37, p = 0.62). Education modified the effect of pRBD on MCI (measured by MoCA: p < 0.001; measured by MMSE: p = 0.061) and gait speed (p = 0.008). Conclusions: Our findings suggest that pRBD increases the risk of cognitive/motor impairments for a community-dwelling older population, and education could alleviate the negative effects. These findings implicate that education may have beneficial effects on delaying the onset of cognitive/motor decline in pRBD subjects.
Diagnostic Performance of Donor-Derived Plasma Cell-Free DNA Fraction for Antibody-Mediated Rejection in Post Renal Transplant Recipients: A Prospective Observational Study

Objective To evaluate the diagnostic performance of donor-derived plasma cell-free DNA (cfDNA) in discriminating antibody-mediated rejection (ABMR) or de novo donor-specific antibodies (DSA) without histological lesions in kidney allograft recipients. Methods In this prospective single center observational study, we enrolled kidney allograft recipients between November, 2016 and September, 2017 at the First Affiliated Hospital of Sun Yat-sen University. Kidney allograft recipients with ABMR, de novo DSA but no histological lesions or negative DSA, and stable renal function were included. The plasma cfDNA fraction was measured using a targeted, single nucleotide polymorphism (SNP)-based assay. Pathological diagnosis was made according to the 2015 Banff Kidney Rejection Classification. The area under the ROC curve (AUC-ROC) was determined using the bootstrapping method to estimate median and 95% confidence interval (95% CI). The sensitivity, specificity and Youden index, positive predictive value (PPV), and negative predictive value (NPV) were calculated for specific cfDNA fractions. Results Totally 37 consecutive patients received kidney allografts, including 18 recipients in the ABMR group and 19 recipients in the stable allograft group (7 DSA-positive and 12 DSA-negative). All patients in the ABMR group were DSA positive and 7 patients in the stable group were DSA positive but had no pathologically proven ABMR. The median donor-derived plasma cfDNA fraction was 2.4% (Q1 1.52% -Q3 3.70%) in the ABMR group, and was significantly higher than that of the stable group (0.65%, Q1 0.57% -Q3 0.97%; P < 0.001), but comparable with that of the DSA-positive patients in the stable allograft group (P = 0.074). The AUC-ROC of cfDNA was 0.90 (95% CI, 0.79–0.98). When a cfDNA threshold of 1% was chosen, it had a sensitivity of 88.9% and a specificity of 73.7%. The PPV was 76.2% and the NPV was 87.5%. Conclusion Donor-derived plasma cfDNA fraction increased in kidney allograft recipients with ABMR. Detection of donor-derived plasma cfDNA fraction may contribute to the discrimination between ABMR and stable renal allograft function and may aid early recognition of earlier stage antibody-mediated injury.
Response of Bacterial and Fungal Soil Communities to Chinese Fir (Cunninghamia lanceolate) Long-Term Monoculture Plantations

Successive rotation and monoculture, as common silvicultural practices, are extensively applied worldwide, particularly in subtropical Chinese fir (Cunninghamia lanceolata) plantations in southern China. Although regeneration failure and productivity decline are frequently observed in continuous monoculture plantations, the potential mechanisms are still unclear. In this study, high-throughput sequencing was used to compare the diversity and composition of bacterial and fungal communities among different generations of Chinese fir plantation (first rotation, FRP; second rotation, SRP; third rotation, TRP) and natural forest (NF) in December and June. Our results showed significant declines in richness and diversity of bacterial and fungal communities in TRP compared with FRP and SRP, but no significant difference between FRP and SRP. The fungal phyla with high relative abundance were Basidiomycota (12.9–76.9%) and Ascomycota (14.3–52.8%), while the bacterial phyla with high relative abundance were Acidobacteria (39.1–57.7%) and Proteobacteria (21.2–39.5%) in all treatments at both sampling months. On average, the relative abundance of Basidiomycota in TRP increased by 53.4%, while that of Ascomycota decreased by 37.1% compared with FRP and SRP. Moreover, soil NH4+–N, pH, and DOC appear to be the key factors in shaping the fungal communities, while soil NH4+–N, DOCN, and AP primarily drive the changes in bacterial communities. Collectively, our findings highlighted the alteration of soil bacterial and fungal communities induced by changes in soil nutrient environment in different generations of continuously cultivated Chinese fir plantation.