Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiometabolic health in premature ovarian insufficiency

Abstract Premature ovarian insufficiency (POI) is an increasing public health problem with a prevalence now approaching 4%. POI results in adverse effects on the skeleton and central nervous system as well as disturbances of metabolic and cardiological factors that predispose to a major increased risk of cardiovascular disease (CVD). This article reviews the effects of the premature loss of ovarian function on lipids and lipoproteins, glucose and insulin metabolism, body composition, hemostasis and blood pressure, together with effects on the development of metabolic syndrome and diabetes mellitus. The article examines the effects of POI on vascular endothelial function and inflammation that result in arterial disease, and reviews the effects of hormone replacement therapy (HRT) on these various metabolic processes and on cardiovascular outcomes. It is essential that women with POI receive hormonal treatment to help prevent the development of CVD, and that this treatment is continued at least until the normal age of menopause. It appears that HRT has a more favorable effect than the combined oral contraceptive, but larger clinical trials are needed to establish the optimal treatment. Other therapeutic measures may need to be added to correct existing metabolic abnormalities and, in particular, attention to lifestyle factors such as diet and exercise must be encouraged.
The Rac-GAP alpha2-Chimaerin Signals via CRMP2 and Stathmins in the Development of the Ocular Motor System

A precise sequence of axon guidance events is required for the development of the ocular motor system. Three cranial nerves grow toward, and connect with, six extraocular muscles in a stereotyped pattern, to control eye movements. The signaling protein alpha2-chimaerin (α2-CHN) plays a pivotal role in the formation of the ocular motor system; mutations in CHN1, encoding α2-CHN, cause the human eye movement disorder Duane Retraction Syndrome (DRS). Our research has demonstrated that the manipulation of α2-chn signaling in the zebrafish embryo leads to ocular motor axon wiring defects, although the signaling cascades regulated by α2-chn remain poorly understood. Here, we demonstrate that several cytoskeletal regulatory proteins—collapsin response mediator protein 2 (CRMP2; encoded by the gene dpysl2), stathmin1, and stathmin 2—bind to α2-CHN. dpysl2, stathmin1, and especially stathmin2 are expressed by ocular motor neurons. We find that the manipulation of dpysl2 and of stathmins in zebrafish larvae leads to defects in both the axon wiring of the ocular motor system and the optokinetic reflex, impairing horizontal eye movements. Knockdowns of these molecules in zebrafish larvae of either sex caused axon guidance phenotypes that included defasciculation and ectopic branching; in some cases, these phenotypes were reminiscent of DRS. chn1 knock-down phenotypes were rescued by the overexpression of CRMP2 and STMN1, suggesting that these proteins act in the same signaling pathway. These findings suggest that CRMP2 and stathmins signal downstream of α2-CHN to orchestrate ocular motor axon guidance and to control eye movements. SIGNIFICANCE STATEMENT The precise control of eye movements is crucial for the life of vertebrate animals, including humans. In humans, this control depends on the arrangement of nerve wiring of the ocular motor system, composed of three nerves and six muscles, a system that is conserved across vertebrate phyla. Mutations in the protein alpha2-chimaerin have previously been shown to cause eye movement disorders (squint) and axon wiring defects in humans. Our recent work has unraveled how alpha2-chimaerin coordinates axon guidance of the ocular motor system in animal models. In this article, we demonstrate key roles for the proteins CRMP2 and stathmin 1/2 in the signaling pathway orchestrated by alpha2-chimaerin, potentially giving insight into the etiology of eye movement disorders in humans.
An innovative approach to polycystic ovary syndrome

Abstract Myo-inositol and D-chiro-inositol are insulin sensitising agents. In the ovary, myo-inositol acts as second messenger of Follicle Stimulating Hormone (FSH). Both molecules were administered to Polycystic Ovary Syndrome (PCOS) women. The gynaecologist Vittorio Unfer was the first to give specific value to myo-inositol for the treatment of PCOS: this important innovation opened new ways of research to identify efficient therapies based on myo-inositol alone or with low doses of D-chiro-inositol. Significant successes were also gained using myo-inositol in treating male and female infertility. Unfer’s researches allowed to identify “the D-Chiro-Inositol Paradox in the Ovary” and the best myo-inositol/D-chiro-inositol ratio (40:1) for the treatment of PCOS. Furthermore, his studies allowed to improve the inositol’s efficacy using alpha-lactalbumin. As shown in this review, the main stages of Unfer’s scientific career have been closely intertwined with important phases of the recent pharmacological research about the topic.
Mapping the Influence: A Nexus Analysis Approach to Addressing Food Access

ABSTRACT One innovative approach toward addressing community-level food access is nexus analysis. This framework suggests that social actions do not happen outside of context, but rather are embedded within unique political, cultural and economic histories. In this paper, I conduct a case study analysis of the South Memphis Farmers Market (SMFM), a community-based, resident-led farmers market located in South Memphis, TN. Drawing on an understanding that neighborhood-level institutions such as farmers markets serve as an intermediary space to examine the nexus of macro-level (e.g., how resources are drawn within a community) and micro-level processes (e.g., how residents determine what food to buy and who to buy it from), this paper traces the success of the SMFM as an illustration of positive local response to the question of “good food” access. Through its history, location and connection to its predominantly Black patrons, the SMFM was able to effectively address structural and cultural barriers as a means of improving food access. Findings from the study may offer insights to the theorization of culture and space in community-based health campaigns.
ApoA2–256T > C polymorphism interacts with Healthy Eating Index, Dietary Quality Index-International and Dietary Phytochemical Index to affect biochemical markers among type 2 diabetic patients

Abstract Several investigations revealed the association between ApoA2 concentration and lipid profile, inflammation and oxidative stress markers. Dietary habits also play a major role in the health status of individuals with type 2 diabetes mellitus (T2DM). This study aimed to investigate the interaction of ApoA2–256T > C with dietary indexes on ghrelin and leptin hormones together with biochemical markers among individuals with T2DM. A cross-sectional study was conducted on 726 randomly selected individuals with T2DM. A validated FFQ was used to evaluate Healthy Eating Index, Dietary Quality Index-International (DQI-I) and Dietary Phytochemical Index (DPI). ApoA2–256T > C genotypes were detected by real-time-PCR. Ghrelin, leptin and biochemical markers were also assessed. ANCOVA was used for the interaction between the polymorphism and dietary indexes. A significant interaction was observed between ApoA2–256T > C and DQI-I on high-sensitivity C-reactive protein (hs-CRP) level and superoxide dismutase (SOD) activity. Besides, the interaction of the SNP and DPI significantly affected hs-CRP and 8-isoprostane F2α (PGF2α) levels. CC in the second tertile of DPI had the lowest hs-CRP level, and it was elevated due to adhering to DQI-I (Pinteraction = 0·01 and 0·04, respectively). Moreover, T-allele (protective allele) carriers with the highest level of PGF2α and SOD activity were those in the second tertile of DPI and DQI-I, respectively (Pinteraction = 0·03 and 0·007, respectively). SOD activity, hs-CRP and PGF2α concentration may be modified in T-allele carriers and CC by the adherence to DPI and DQI-I, though additional studies are required to confirm these findings.
Process development for cross‐flow diafiltration‐based VLP disassembly: A novel high‐throughput screening approach

Virus‐like particles (VLPs) are particulate structures, which are applied as vaccines or delivery vehicles. VLPs assemble from subunits, named capsomeres, composed of recombinantly expressed viral structural proteins. During downstream processing, in vivo‐assembled VLPs are typically dis‐ and reassembled to remove encapsulated impurities and to improve particle morphology. Disassembly is achieved in a high‐pH solution and by the addition of a denaturant or reducing agent. The optimal disassembly conditions depend on the VLP amino acid sequence and structure, thus requiring material‐consuming disassembly experiments. To this end, we developed a low‐volume and high‐resolution disassembly screening that provides time‐resolved insight into the VLP disassembly progress. In this study, two variants of C‐terminally truncated hepatitis B core antigen were investigated showing different disassembly behaviors. For both VLPs, the best capsomere yield was achieved at moderately high urea concentration and pH. Nonetheless, their disassembly behaviors differed particularly with respect to disassembly rate and aggregation. Based on the high‐throughput screening results, a diafiltration‐based disassembly process step was developed. Compared with mixing‐based disassembly, it resulted in higher yields of up to 0.84 and allowed for integrated purification. This process step was embedded in a filtration‐based process sequence of disassembly, capsomere separation, and reassembly, considerably reducing high‐molecular‐weight species.
Trends in asymptomatic STI among HIV-positive MSM and lessons for systematic screening

The burden of STIs is particularly high in HIV-infected MSM patients. A recent increase in STIs prevalence has been noticed in the US and western European countries. We aim to assess trends in asymptomatic STIs following the publication of recommendations for STIs screening, i.e. Chlamydia (CT) and gonorrhea (NG). Seventeen centers located in the Paris area participated in the study. All asymptomatic HIV-infected MSM patients attending a follow up consultation were proposed to participated in the study. Asymptomatic patients were included over 2 periods: period 1 from April to December 2015 and period 2 from September to December 2017. Etiologic diagnosis of STIs including hepatitis B, C, syphilis, was performed using a serological test, including a non-treponemal titer with a confirmatory treponemal assay for syphilis. CT and NG were screened using a nucleic acid amplification test (NAATs) on 3 anatomical sites, i.e. urine, rectal and pharyngeal. Overall, 781 patients were included: 490 and 291 in periods 1 and 2 respectively. Asymptomatic CT, NG, and syphilis were diagnosed in 7.5%, 4.8% and, 4.2% respectively. The rate of patients having a multisite asymptomatic infection was 10.2% and 21.1% for CT and NG respectively. The most frequently involved anatomical sites for CT and NG asymptomatic infections were anorectal (66.1% and 55.2% respectively) and pharyngeal (47.4% and 60.5% respectively). CT and NG asymptomatic infection increased by 1.3- and 2-fold respectively between the two periods while syphilis decreased by 3 folds. Our results encourage to reconsider multisite screening for CT and NG in asymptomatic HIV positive MSM as the yield of screening urinary samples only might be low. Despite the more systematic STI screening of asymptomatic HIV positive MSM the prevalence of STI is increasing in MSM in France. Therefore, this strategy has not led to alter CT and NG transmission. The decrease of syphilis might involve self-medication by doxycycline, and the intensification of syphilis screening.
Trust, Perceptions of Risks and Benefits, and Normative Acceptance of Approaches for Restoring American Chestnut Trees

This article examined trust, perceived risks and benefits, and normative acceptance associated with using breeding and genetic engineering (GE) to restore American chestnut (AC) trees. Questionnaires were completed by a random representative sample of the public in the United States (n = 278) and a purposive sample of forest interest groups (FIG) such as scientists and managers (n = 195). These concepts were examined in relation to breeding (breed the AC with chestnut trees from Asia) and GE (add the oxalate oxidase [OxO] gene from bread wheat to the AC) approaches for mitigating chestnut blight and restoring AC trees. The public sample considered adding the gene from bread wheat (GE) to be more beneficial and slightly more acceptable, but also slightly riskier, compared to the breeding approach. The FIGs viewed the breeding approach to be more acceptable, less risky, and more beneficial than the GE approach. The FIGs viewed both approaches as less risky, more beneficial, and more acceptable than did the public sample. Path analysis showed that: (i) perceived environmental benefits were the strongest predictors of normative acceptance of both approaches for the public sample, (ii) perceived environmental risks were the strongest predictors of acceptance of both approaches for the FIGs, (iii) human benefits and risks were mostly unrelated to acceptance, and (iv) trust in government agencies charged with managing forests was only weakly associated with benefits, risks, and acceptance. Implications of these results for both research and management were discussed.
Nursing students’ attitude on the practice of e-learning: A cross-sectional survey amid COVID-19 in Nepal

Introduction In present days, the use of information technology (IT) in education is unquestionable. The mounting advancement of IT has changed the scenario of education. With the emergence of the current COVID-19 situation, it has undoubtedly provided a solution to most of our educational needs when all educational institutions remained closed due to the pandemic. This study aims to identify the nursing students’ attitude towards the practice of e-learning amidst COVID-19. Methods A descriptive web-based cross-sectional study was conducted among nursing students with a sample size of 470. A self-administered validated questionnaire along with a standard tool to measure the attitude was used for data collection. Data were analyzed using SPSS. Results The mean ± SD age of the respondents was 20.91± 1.55 years. The majority (76.4%) of the respondents used mobile for their study and 90.4% used Wi-Fi for the internet source. The main advantage of e-learning was stated as the ability to stay at home (72.1%) followed by the reduced cost of accommodation and transport (51.3%) whereas the internet problem (81.7%) was the major disadvantage followed by technical issues (65.5%). Only about 34% of the students found e-learning as effective as traditional face-to-face learning. The mean scores for the domains: perceived usefulness, intention to adapt, distant use of e-learning, ease of learning, technical support, and learning stressors were 3.1, 3.1, 3.8, 2.9, 2.9, and 2.5 respectively. Overall, 58.9% had a favorable attitude regarding e-learning. There was no significant association of overall attitude regarding e-learning with selected socio-demographic variables whereas it was positively associated with all of its six domains. All the domains were positively correlated with each other except for ease of learning with technical support and distant use, and technical support with learning stressor and distant use. Learning stressor versus distant use was negatively correlated with each other. Conclusion Though e-learning was implemented as a substitute during the pandemic, almost half of the nursing students showed a positive attitude regarding e-learning. The majority of the students had internet problems and technological issues. If e-learning can be made user-friendly with reduced technical barriers supplemented with programs that can enhance practical learning abilities, e-learning can be the vital alternative teaching method and learning in the nursing field.
The rein-type arthroscopic capsular suture for triangular fibrocartilage complex foveal tears: midterm results for 90 patients

We describe an arthroscopic rein-type capsular suture that approximates the triangular fibrocartilage complex to the anatomical footprint, and report the results at a minimum 12 month follow-up. The procedure involves two 3-0 polydioxanone horizontal mattress sutures inserted 1.5 cm proximal to the 6-R and 6-U portals to obtain purchase on the dorsal and anterior radioulnar ligaments, respectively. The two sutures work as a rein to approximate the triangular fibrocartilage complex to the fovea. Ninety patients with Type IB triangular fibrocartilage complex injuries were included retrospectively. The 12-month postoperative Modified Mayo Wrist scores, Disabilities of Arm, Shoulder and Hand scores and visual analogue scale for pain showed significant improvements on preoperative values. Postoperative range of wrist motion, grip strength and ultrasound assessment of the distal radioulnar joint stability were comparable with the normal wrist. The patients had high satisfaction scores for surgery. There were minor complications of knot irritation. No revision surgery for distal radioulnar joint instability was required. It is an effective and technically simple procedure that provides a foveal footprint contact for the triangular fibrocartilage complex. Level of evidence: IV
Intratumor CMS Heterogeneity Impacts Patient Prognosis in Localized Colon Cancer

Purpose: The consensus molecular subtypes (CMS) represent a significant advance in the understanding of intertumor heterogeneity in colon cancer. Intratumor heterogeneity (ITH) is the new frontier for refining prognostication and understanding treatment resistance. This study aims at deciphering the transcriptomic ITH of colon cancer and understanding its potential prognostic implications. Experimental Design: We deconvoluted the transcriptomic profiles of 1,779 tumors from the PETACC8 trial and 155 colon cancer cell lines as weighted sums of the four CMSs, using the Weighted In Silico Pathology (WISP) algorithm. We assigned to each tumor and cell line a combination of up to three CMS subtypes with a threshold above 20%. Results: Over 55% of tumors corresponded to mixtures of at least two CMSs, demonstrating pervasive ITH in colon cancer. Of note, ITH was associated with shorter disease-free survival (DFS) and overall survival, [HR, 1.34; 95% confidence interval (CI; 1.12–1.59), 1.40, 95% CI (1.14–1.71), respectively]. Moreover, we uncovered specific combinations of CMS associated with dismal prognosis. In multivariate analysis, ITH represents the third parameter explaining DFS variance, after T and N stages. At a cellular level, combined WISP and single-cell transcriptomic analysis revealed that most colon cancer cell lines are a mixture of cells falling into different CMSs, indicating that ITH may correspond to distinct functional statuses of colon cancer cells. Conclusions: This study shows that CMS-based transcriptomic ITH is frequent in colon cancer and impacts its prognosis. CMS-based transcriptomic ITH may correspond to distinct functional statuses of colon cancer cells, suggesting plasticity between CMS-related cell populations. Transcriptomic ITH deserves further assessment in the context of personalized medicine.
The effect of mental health on sleep quality of front-line medical staff during the COVID-19 outbreak in China: A cross-sectional study

Background The 2019 coronavirus disease (COVID-19) pandemic is a public health emergency of international concern and poses a challenge to the mental health and sleep quality of front-line medical staff (FMS). The aim of this study was to investigate the sleep quality of FMS during the COVID-19 outbreak in China and analyze the relationship between mental health and sleep quality of FMS. Methods From February 24, 2020 to March 22, 2020, a cross-sectional study was performed with 543 FMS from a medical center in Western China. A self-reported questionnaire was used to collect data anonymously. The following tests were used: The Self-Rating Anxiety Scale (SAS) for symptoms of anxiety, the Beck Depression Inventory (BDI) for depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) for sleep quality assessment. Results Of the 543 FMS, 216 (39.8%) were classified as subjects with poor sleep quality. Anxiety (P<0.001), depression (P<0.001), and the prevalence of those divorced or widowed (P<0.05) were more common in FMS with poor sleep quality than in participants with good sleep quality. The FMS exhibiting co-occurrence of anxiety and depression were associated with worse scores on sleep quality than those medical staff in the other three groups/categories. The difference in sleep quality between the FMS with only depression and the FMS experiencing co-occurrence of anxiety and depression was statistically significant (P<0.05). However, there was no significant difference in sleep quality between the FMS experiencing only anxiety and the FMS with co-occurrence of anxiety and depression (P > 0.05). Conclusions During the COVID-19 pandemic, there was a noteworthy increase in the prevalence of negative emotions and sentiments among the medical staff, along with poor overall sleep quality. We anticipate that this study can stimulate more research into the mental state of FMS during outbreaks and other public health emergencies. In addition, particular attention must be paid to enhance the sleep quality of FMS, along with better planning and support for FMS who are continuously exposed to the existing viral epidemic by virtue of the nature of their profession.
The Chronic Lymphocytic Leukemia Comorbidity Index (CLL-CI): A Three-Factor Comorbidity Model

Purpose: Comorbid medical conditions define a subset of patients with chronic lymphocytic leukemia (CLL) with poor outcomes. However, which comorbidities are most predictive remains understudied. Experimental Design: We conducted a retrospective analysis from 10 academic centers to ascertain the relative importance of comorbidities assessed by the cumulative illness rating scale (CIRS). The influence of specific comorbidities on event-free survival (EFS) was assessed in this derivation dataset using random survival forests to construct a CLL-specific comorbidity index (CLL-CI). Cox models were then fit to this dataset and to a single-center, independent validation dataset. Results: The derivation and validation sets comprised 570 patients (59% receiving Bruton tyrosine kinase inhibitor, BTKi) and 167 patients (50% receiving BTKi), respectively. Of the 14 CIRS organ systems, three had a strong and stable influence on EFS: any vascular, moderate/severe endocrine, moderate/severe upper gastrointestinal comorbidity. These were combined to create the CLL-CI score, which was categorized into 3 risk groups. In the derivation dataset, the median EFS values were 58, 33, and 20 months in the low, intermediate, and high-risk groups, correspondingly. Two-year overall survival (OS) rates were 96%, 91%, and 82%. In the validation dataset, median EFS values were 81, 40, and 23 months (two-year OS rates 97%/92%/88%), correspondingly. Adjusting for prognostic factors, CLL-CI was significantly associated with EFS in patients treated with either chemo-immunotherapy or with BTKi in each of our 2 datasets. Conclusions: The CLL-CI is a simplified, CLL-specific comorbidity index that can be easily applied in clinical practice and correlates with survival in CLL.