Miracle-dz/UniFAR-FTUs huggingface dataset:
Recent advances from metabolomics and lipidomics application in alzheimer’s disease inspiring drug discovery

ABSTRACT Introduction: Although age is a major risk factor for Alzheimer’s disease (AD), it is not an inevitable consequence of aging nor is it exclusively an old-age disease. Several other major risk factors for AD are strongly associated with metabolism and include lack of exercise, obesity, diabetes, high blood pressure and cholesterol, over-consumption of alcohol and depression in addition to low educational level, social isolation, and cognitive inactivity. Approaches for Alzheimer prevention and treatment through manipulation of metabolism and utilization of active metabolites have great potential either as a primary or secondary treatment avenue or as a preventative strategy in high-risk individuals. Areas covered: This review outlines the current knowledge concerning the relationship between AD and metabolism and the novel treatments attempting to correct changes in AD patients determined through metabolomics or lipidomic analyses. Expert opinion: Metabolites are one of the main driving factors and indicators of AD and can offer many possible avenues for prevention and treatment. However, with the highly interconnected effects of metabolites and metabolism, as well as the many different routes for metabolism dysfunction, successful treatment would have to include the correction of metabolic errors as well as errors in transport and metabolite processing in order to affect and revert AD progression.
Trends in Referrals to a Pediatric Transgender Clinic

Referrals for pediatric TGNC patients increased significantly over 3 years. Referrals were mostly for cross-sex hormones and/or blockers and surgery, and needs varied by age group. OBJECTIVES: We characterized referral trends over time at a transgender clinic within an integrated health system in Northern California. We identified the transition-related requests of pediatric transgender and gender-nonconforming patients and evaluated differences in referrals by age group. METHODS: Medical records were analyzed for all patients <18 years of age in the Kaiser Permanente Northern California health system who were referred to a specialty transgender clinic between February 2015 and June 2018. Trends in treatment demand, demographic data, service requests, and surgical history were abstracted from medical charts and analyzed by using descriptive statistics. RESULTS: We identified 417 unique transgender and gender-nonconforming pediatric patients. The median age at time of referral was 15 years (range 3–17). Most (62%) identified on the masculine spectrum. Of the 203 patients with available ethnicity data, 68% were non-Hispanic. During the study period, the clinic received a total of 506 referrals with a significant increase over time (P < .001). Most referrals were for requests to start cross-sex hormones and/or blockers (34%), gender-affirming surgery (32%), and mental health (27%). Transition-related requests varied by age group: younger patients sought more mental health services, and older patients sought hormonal and surgical services. Eighty-nine patients underwent gender-affirming surgeries, mostly before age 18 and most frequently mastectomies (77%). CONCLUSIONS: The increase in referrals supports the need for expanded and accessible health care services for this population. The transition-related care of patients in this large sample varied by age group, underscoring the need for an individualized approach to gender-affirming care.
A relatively wide-bandgap and air-stable donor polymer for fabrication of efficient semitransparent and tandem organic photovoltaics

Significance Organic semiconductors are promising candidates for fabrication of semitransparent and tandem solar cells due to their low-cost processing, light weight, and solution processability. Here, we synthesize a donor copolymer (poly{[2,7-(5,5-didecyl-5H-1,8-dithia-as-indacenone)]-alt-[5,5-(5′,6′-dioctyloxy-4′,7′-di-2-thienyl-2′,1′,3′-benzothiadiazole)]} [PDTIDTBT]) with relatively large bandgap and good stability. We show a stable and efficient semitransparent solar cell using graphene as electrode and achieve a power conversion efficiency (PCE) of 4.75% with average visible transmittance of 55%. We also demonstrate the application of the PDTIDTBT donor for tandem solar cell with PCE of up to 8.83% and long-term stability. Organic photovoltaics (OPVs) have attracted tremendous attention in the field of thin-film solar cells due to their wide range of applications, especially for semitransparent devices. Here, we synthesize a dithiaindacenone-thiophene-benzothiadiazole-thiophene alternating donor copolymer named poly{[2,7-(5,5-didecyl-5H-1,8-dithia-as-indacenone)]-alt-[5,5-(5′,6′-dioctyloxy-4′,7′-di-2-thienyl-2′,1′,3′-benzothiadiazole)]} (PDTIDTBT), which shows a relatively wide bandgap of 1.82 eV, good mobility, and high transmittance and ambient stability. In this work, we fabricate an OPV device using monolayer graphene as top electrode. Due to the stability of PDTIDTBT in air and water, we use a wet transfer technique for graphene to fabricate semitransparent OPVs. We demonstrate OPVs based on the PDTIDTBT:Phenyl-C61/71-butyric acid methyl ester (PCBM) blend with maximum power conversion efficiencies (PCEs) of 6.1 and 4.75% using silver and graphene top electrodes, respectively. Our graphene-based device shows a high average visible transmittance (AVT) of 55%, indicating the potential of PDTIDTBT for window application and tandem devices. Therefore, we also demonstrate tandem devices using the PDTIDTBT:Phenyl-C61-butyric acid methyl ester (PC60BM) blend in both series and parallel connections with average PCEs of 7.3 and 7.95%, respectively. We also achieve a good average PCE of 8.26% with an average open circuit voltage (Voc) of 1.79 V for 2-terminal tandem OPVs using this blend. Based on tandem design, an OPV with PCE of 6.45% and AVT of 38% is demonstrated. Moreover, our devices show improved shelf life and ultraviolet (UV) stability (using CdSe/ZnS core shell quantum dots [QDs]) in ambient with 45% relative humidity.
Facteurs cliniques périnatals et paramètres biologiques prédictifs du pronostic chez l'enfant prématuré

L’objectif de ce travail etait de decrire les facteurs biologiques precoces influencant le pronostic des enfants grands prematures. A partir d’une population de 1 067 enfants admis en reanimation neonatale au CHU de Dijon de 2001 a 2008 et faisant l’objet d’un recueil prospectif de donnees clinico-biologiques perinatales, deux objectifs de recherche ont ete identifies : 1) evaluer l’impact des troubles de la chloremie au cours de l’adaptation postnatale sur la morbidite neurologique ; 2) caracteriser la possible association entre l’hypoprotidemie du premier jour de vie (J1) et le pronostic defavorable. Ces objectifs ont ete approfondis dans 4 etudes, realisees sur la population initiale et sur 3 autres cohortes de grands prematures. Nous avons observe que l’hyperchloremie entraine une acidose metabolique severe dans les 7 a 10 premiers jours de vie sans que ceci ne s’associe a un pronostic neurologique defavorable (hemorragie intraventriculaire et/ou paralysie cerebrale a 18 mois d’âge corrige). Les resultats ont montre l’importance de controler les apports de chlore des medicaments et de la nutrition parenterale, afin de prevenir toute acidose metabolique indesirable apres la naissance. Les etudes sur la protidemie ont montre que l’hypoprotidemie a J1 est un facteur independant associe au deces ou a la survie avec anomalies neurologiques severes et que son pouvoir predictif de pronostic defavorable est comparable a celui d’autres scores de gravite valides. Ce travail contribue a la comprehension des facteurs perinatals influencant le pronostic du grand premature et ouvre de nouvelles perspectives de recherche sur la prise en charge de ces enfants vulnerables.
Correlation between the Expression of PD-L1 and Clinicopathological Parameters in Triple Negative Breast Cancer Patients.

Objective Triple-negative breast cancer (TNBC) is a heterogenous group of tumors with no estrogen receptor (ER), progesterone receptor (PR) and Cerb-B2/HER2 expression. Programmed death ligand-1 (PD-L1) is a transmembrane protein located on both non-tumor and tumor cells and it has been shown to be associated with the escape of tumor cells from the immune system. PD-L1-targeted therapy alone or in combination is now an alternative strategy in several aggressive tumor types. In this respect, TNBC is a potential candidate having limited treatment options and poor outcome. Material and Methods Sixty-one breast cancers with no expression of ER, PR and Cerb-B2/HER2 were chosen to study PD-L1 immunohistochemistry. PD-L1 staining and its correlation with main clinicopathological parameters were evaluated. Results The percentage of PD-L1 positivity was 37.7% and 47.5% in tumor and tumor microenvironment, respectively. The positivity rate was higher in breast carcinomas with medullary features (83.3%) and metaplastic carcinoma (66.6%) subgroups. PD-L1 expression of tumors was positively correlated with their Ki-67 score and PD-L1 positivity of the tumor microenvironment. No significant relationship was found between the other variables. Conclusion PD-L1 expression rate was remarkable both in the tumor and the tumor microenvironment of TNBCs. Larger cohorts of TNBC are required to further describe their PD-L1 expression characteristics and help standardize PD-L1 immunohistochemistry assays in these tumors.
Recovery from impaired working memory performance during chronic Δ-9-tetrahydrocannabinol administration to adolescent rhesus monkeys

Background: The relationship between adolescent cannabis use and susceptibility to persistent cognitive impairments is poorly understood. Aims: We examined the effects of repeated exposure to Δ-9-tetrahydrocannabinol (THC) on reinforcement-related learning and performance of spatial working memory (WM) tasks of varying difficulty in adolescent monkeys. Methods: Seven pairs of male adolescent rhesus monkeys, matched for baseline cognitive performance, received vehicle or THC intravenously 5 days/week for 12 months. Performance on 4-item spatial WM trials was assessed throughout the 12-month study period. At the 6-month time point, more difficult novel and distractor 8-item spatial WM trials were added. Residual effects on performance were determined 23 or 71 h after THC or vehicle administration throughout the study. Results/outcomes: Relative to vehicle-exposed animals, repeated THC exposure was initially associated with significantly slower improvement in performance accuracy on 4-item spatial WM trials; however, this performance difference gradually diminished such that by month 12, accuracy did not significantly differ between vehicle and THC groups. Similarly, for the novel and distractor 8-item trials introduced at month 6, performance accuracy improved more slowly in the THC than in the vehicle group, despite comparable performance between groups on the 4-item task during this same period. Conclusions/interpretation: These findings suggest that compared to vehicle exposure, THC exposure during adolescence impairs the reinforcement-related learning process required for improved performance on spatial WM tasks, but this impairment might be overcome with continued training, even in the face of ongoing THC exposure.
Transcriptome Characterization of Reverse Development in Turritopsis dohrnii (Hydrozoa, Cnidaria)

Medusae of Turritopsis dohrnii undergo reverse development in response to physical damage, adverse environmental conditions, or aging. Senescent, weakened or damaged medusae transform into a cluster of poorly differentiated cells (known as the cyst stage), which metamorphose back into a preceding life cycle stage, the polyp. During the metamorphosis, cell transdifferentiation occurs. The cyst represents the intermediate stage between a reverting medusa and a healthy polyp, during which cell transdifferentiation and tissue reorganization take place. Here we characterize and compare the transcriptomes of the polyp and newborn medusa stages of T. dohrnii with that of the cyst, to identify biological networks potentially involved in the reverse development and transdifferentiation processes. The polyp, medusa and cyst of T. dohrnii were sequenced through Illumina RNA-sequencing and assembled using a de novo approach, resulting in 92,569, 74,639 and 86,373 contigs, respectively. The transcriptomes were annotated and comparative analyses among the stages identified biological networks that were significantly over-and under-expressed in the cyst as compared to the polyp and medusa stages. Biological processes that occur at the cyst stage such as telomerase activity, regulation of transposable elements and DNA repair systems, and suppression of cell signaling pathways, mitotic cell division and cellular differentiation and development may be involved in T. dohrnii’s reverse development and transdifferentiation. Our results are the first attempt to understand T. dohrnii’s life-cycle reversal at the genetic level, and indicate possible avenues of future research on developmental strategies, cell transdifferentiation, and aging using T. dohrnii as a non-traditional in vivo system.
Comparison of Vessel Density Reduction in the Deep and Superficial Capillary Plexuses in Branch Retinal Vein Occlusion

Purpose: To quantify the susceptibility of the deep capillary plexus (DCP) in comparison with that of the superficial capillary plexus (SCP) in eyes with branch retinal vein occlusion (BRVO) using swept-source optical coherence tomography angiography (SS-OCTA). Methods: SS-OCTA (TritonTM; Topcon, Tokyo, Japan) scans (3 × 3 mm) of 41 patients with BRVO were retrospectively analyzed. The mean vessel densities (VDs) of the SCP and the DCP were calculated in eyes with BRVO using the ImageJ program (National Institutes of Health, Bethesda, MD, USA) and compared with those in the normal fellow eye without any morbidity or unaffected sector in the BRVO eye. Results: The reduction rate of mean VD in SCP and DCP between the affected and unaffected sector of eyes with BRVO was 13.88 and 24.60%, respectively. Additionally, the reduction rate of mean VD in the SCP and DCP in the affected sector of BRVO eyes versus the corresponding sector of fellow eyes was 13.31 and 24.49%, respectively. Conclusion: The DCP was 1.77–1.84 times more affected than the SCP by ischemic damage in eyes with BRVO.
Ultra-processed foods, incident overweight and obesity, and longitudinal changes in weight and waist circumference: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Abstract Objective: To evaluate the association of ultra-processed food (UPF) consumption with gains in weight and waist circumference, and incident overweight/obesity, in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort. Design: We applied FFQ at baseline and categorized energy intake by degree of processing using the NOVA classification. Height, weight and waist circumference were measured at baseline and after a mean 3·8-year follow-up. We assessed associations, through Poisson regression with robust variance, of UPF consumption with large weight gain (1·68 kg/year) and large waist gain (2·42 cm/year), both being defined as ≥90th percentile in the cohort, and with incident overweight/obesity. Setting: Brazil. Participants: Civil servants of Brazilian public academic institutions in six cities (n 11 827), aged 35–74 years at baseline (2008–2010). Results: UPF provided a mean 24·6 (sd 9·6) % of ingested energy. After adjustment for smoking, physical activity, adiposity and other factors, fourth (>30·8 %) v. first (<17·8 %) quartile of UPF consumption was associated (relative risk (95 % CI)) with 27 and 33 % greater risk of large weight and waist gains (1·27 (1·07, 1·50) and 1·33 (1·12, 1·58)), respectively. Similarly, those in the fourth consumption quartile presented 20 % greater risk (1·20 (1·03, 1·40)) of incident overweight/obesity and 2 % greater risk (1·02; (0·85, 1·21)) of incident obesity. Approximately 15 % of cases of large weight and waist gains and of incident overweight/obesity could be attributed to consumption of >17·8 % of energy as UPF. Conclusions: Greater UPF consumption predicts large gains in overall and central adiposity and may contribute to the inexorable rise in obesity seen worldwide.
Lung Biopsy Findings in Severe Pulmonary Illness Associated With E-Cigarette Use (Vaping).

OBJECTIVES The aim of this report is to describe the lung biopsy findings in vaping-associated pulmonary illness. METHODS Lung biopsies from eight patients with vaping-associated pulmonary illness were reviewed. RESULTS The biopsies were from eight men (aged 19-61 years) with respiratory symptoms following e-cigarette use (vaping). Workup for infection was negative in all cases, and there was no evidence for other etiologies. Imaging showed diffuse bilateral ground-glass opacities in all patients. Most recovered with corticosteroid therapy, while one died. Lung biopsies (seven transbronchial, one surgical) showed acute lung injury, including organizing pneumonia and/or diffuse alveolar damage. Common features were fibroblast plugs, hyaline membranes, fibrinous exudates, type 2 pneumocyte hyperplasia, and interstitial organization. Some cases featured a sparse interstitial chronic inflammatory infiltrate. Although macrophages were present within the airspaces in all cases, this feature was not prominent, and findings typical of exogenous lipoid pneumonia were absent. CONCLUSIONS The histopathology of acute pulmonary illness related to e-cigarette use (vaping) is characterized by acute lung injury patterns, supporting the contention that vaping can cause severe lung damage.
Utility of DNA Next-Generation Sequencing and Expanded Quantitative Urine Culture in Diagnosis and Management of Chronic or Persistent Lower Urinary Tract Symptoms

Many patients suffer from chronic, irritative lower urinary tract symptoms (LUTS). The evaluation and management of these patients have proven difficult with the use of standard diagnostic tools, including urinalysis and urine culture. The growing body of literature on the urinary microbiome has looked at the possible implications of the bladder microbiome and dysbiosis, or perturbations in the microbiome, in conditions associated with chronic LUTS. ABSTRACT Many patients suffer from chronic, irritative lower urinary tract symptoms (LUTS). The evaluation and management of these patients have proven difficult with the use of standard diagnostic tools, including urinalysis and urine culture. The growing body of literature on the urinary microbiome has looked at the possible implications of the bladder microbiome and dysbiosis, or perturbations in the microbiome, in conditions associated with chronic LUTS. Disorders such as recurrent urinary tract infections (UTIs) and interstitial cystitis have been studied utilizing 16S rRNA rapid next-generation gene sequencing (NGS) and expanded quantitative urine culture (EQUC). In this article, we first present a brief review of the literature describing the current understanding of the urinary microbiome and the features and applications of NGS and EQUC. Next, we discuss the conditions most commonly associated with chronic, persistent LUTS and present the limitations of current diagnostic practices utilized in this patient population. We then review the limited data available surrounding treatment efficacy and clinical outcomes in patients who have been managed based on results provided by these two recently established diagnostic tools (DNA NGS and/or EQUC). Finally, we propose a variety of clinical scenarios in which the use of these two techniques may affect patients’ clinical outcomes.
The European Medicines Agency Review of Kymriah (Tisagenlecleucel) for the Treatment of Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma.

Chimeric antigen receptor (CAR)-engineered T-cell therapy is becoming one of the most promising approaches in the treatment of cancer. On June 28, 2018, the Committee for Advanced Therapies (CAT) and the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Kymriah for pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse after transplant, or in second or later relapse and for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. Kymriah became one of the first European Union-approved CAR T therapies. The active substance of Kymriah is tisagenlecleucel, an autologous, immunocellular cancer therapy that involves reprogramming the patient's own T cells to identify and eliminate CD19-expressing cells. This is achieved by addition of a transgene encoding a CAR. The benefit of Kymriah was its ability to achieve remission with a significant duration in patients with ALL and an objective response with a significant duration in patients with DLBCL. The most common hematological toxicity was cytopenia in both patients with ALL and those with DLBCL. Nonhematological side effects in patients with ALL were cytokine release syndrome (CRS), infections, secondary hypogammaglobulinemia due to B-cell aplasia, pyrexia, and decreased appetite. The most common nonhematological side effects in patients with DLBCL were CRS, infections, pyrexia, diarrhea, nausea, hypotension, and fatigue. Kymriah also received an orphan designation on April 29, 2014, following a positive recommendation by the Committee for Orphan Medicinal Products (COMP). Maintenance of the orphan designation was recommended at the time of marketing authorization as the COMP considered the product was of significant benefit for patients with both conditions. IMPLICATIONS FOR PRACTICE: Chimeric antigen receptor (CAR)-engineered T-cell therapy is becoming the most promising approach in cancer treatment, involving reprogramming the patient's own T cells with a CAR-encoding transgene to identify and eliminate cancer-specific surface antigen-expressing cells. On June 28, 2018, Kymriah became one of the first EMA approved CAR T therapies. CAR T technology seems highly promising for diseases with single genetic/protein alterations; however, for more complex diseases there will be challenges to target clonal variability within the tumor type or clonal evolution during disease progression. Products with a lesser toxicity profile or more risk-minimization tools are also anticipated.