Miracle-dz/UniFAR-FTUs huggingface dataset:
Influenza vaccine effectiveness in inpatient and outpatient settings in the United States, 2015 - 2018.

BACKGROUND Demonstration of influenza vaccine effectiveness (VE) against hospitalization for severe illness in addition to milder outpatient illness may strengthen vaccination messaging and improve suboptimal uptake in the U.S. Our objective was to compare patient characteristics and VE between U.S. inpatient and outpatient VE networks. METHODS We tested adults ≥18-years with acute respiratory illness (ARI) for influenza within two VE networks, one outpatient- and the other hospital-based, from 2015-2018. We compared age, sex, and chronic high-risk conditions between populations. The test-negative design was used to compare vaccination odds in influenza-positive cases versus influenza-negative controls. We estimated VE using logistic regression adjusting for site, age, sex, race/ethnicity, peak influenza activity, time-to-testing from symptom-onset, season (overall VE) and underlying conditions. VE differences (ΔVE) were assessed with 95% confidence intervals (CI) determined through bootstrapping with significance defined as excluding the null. RESULTS The VE networks enrolled 14,573 (4144 influenza-positive) outpatients and 6769 (1452 influenza-positive) inpatients. Inpatients were older (median 62-years vs. 49-years) and had more high-risk conditions (median 4 vs. 1). Overall influenza VE across seasons was 31% (95%CI:26%-37%) among outpatients and 36% (27%-44%) among inpatients. Strain-specific VE among outpatients versus inpatients was 37% (25%-47%) vs. 53% (37%-64%) against H1N1pdm09, 19% (9%-27%) vs. 23% (8%-35%) against H3N2, and 46% (38%-53%) vs. 46% (31%-58%) against B-viruses. ΔVE was not significant for any comparison across all sites. CONCLUSIONS Inpatients and outpatients with ARI represent distinct populations. Despite comparatively poor health status among inpatients, influenza vaccination was effective in preventing hospitalizations associated with influenza.
A Novel Hybrid Nanosystem Integrating Cytotoxic and Magnetic Properties as a Tool to Potentiate Melanoma Therapy

Cancer is a major health concern and the prognosis is often poor. Significant advances in nanotechnology are now driving a revolution in cancer detection and treatment. The goal of this study was to develop a novel hybrid nanosystem for melanoma treatment, integrating therapeutic and magnetic targeting modalities. Hence, we designed long circulating and pH-sensitive liposomes loading both dichloro(1,10-phenanthroline) copper (II) (Cuphen), a cytotoxic metallodrug, and iron oxide nanoparticles (IONPs). The synthetized IONPs were characterized by transmission electron microscopy and dynamic light scattering. Lipid-based nanoformulations were prepared by the dehydration rehydration method, followed by an extrusion step for reducing and homogenizing the mean size. Liposomes were characterized in terms of incorporation parameters and mean size. High Cuphen loadings were obtained and the presence of IONPs slightly reduced Cuphen incorporation parameters. Cuphen antiproliferative properties were preserved after association to liposomes and IONPs (at 2 mg/mL) did not interfere on cellular proliferation of murine and human melanoma cell lines. Moreover, the developed nanoformulations displayed magnetic properties. The absence of hemolytic activity for formulations under study demonstrated their safety for parenteral administration. In conclusion, a lipid-based nanosystem loading the cytotoxic metallodrug, Cuphen, and displaying magnetic properties was successfully designed.
Change in Body Weight and Long-Term Risk of Stroke and Death in Healthy Men

Supplemental Digital Content is available in the text. Background and Purpose— The importance of weight change for the risk of stroke is not well known. We examined the associations between early- and mid-life weight change and risks of stroke and death during long-term follow-up of healthy men. Methods— We recruited healthy men aged between 40 and 59 years and performed a cardiovascular examination at baseline and again at 7 years. We collected data on weight change since the age of 25 (early-life weight change) and measured weight change from baseline to the visit at 7 years (mid-life weight change). For both weight change periods, participants were divided into the following categories: weight loss, weight gain 0 to 4.9 kg, weight gain 5 to 9.9 kg, and weight gain ≥10 kg. Data on stroke and death were collected up to 35 years, from study visits, hospital records, and the National Cause of Death Registry. We used Cox regression to analyze the associations between weight change during early-life and mid-life and risks of stroke and death. Results— Of the 2014 participants, 2014 (100%) had data on early-life weight change and were followed for a median of 30.1 years, while 1403 had data on mid-life weight change and were followed for a median of 24.6 years. During early-life, compared with those who had weight gain 0 to 4.9 kg, hazard ratio for stroke was 1.46 (95% CI, 1.09–1.95) among those with weight gain 5 to 9.9 kg, 1.39 (95% CI, 1.03–1.87) for those with weight gain ≥10 kg, and 1.46 (95% CI, 0.99–2.11) among those with weight loss. For all-cause death, the hazard ratios were 1.08 (95% CI, 0.92–1.23), 1.14 (95% CI, 0.98–1.33), and 1.29 (95% CI, 1.06–1.56), respectively. During mid-life, there were no significant differences in risk of stroke or death between the groups. Conclusions— Weight increase during early-life, but not mid-life, seems to be associated with increased long-term risk of stroke in healthy men. If these findings can be confirmed, efforts to prevent weight increase should target the younger population.
Morphological Adaptive Radiation Therapy: The impact of weekly anatomical changes

The treatment of mucosal Head and Neck (H+N) cancers with radiotherapy has seen considerable technological development over recent years; from large non-conformal fields, to threeDimensional Conformal Radiation Therapy (3-D CRT) and subsequently the introduction of Intensity Modulated Radiation Therapy (IMRT), Volumetric Modulated Arc Therapy (VMAT) and other radiation therapy delivery techniques, such as proton therapy. When compared to older “conventional” techniques, the IMRT planning process results in improved dose to tumour volumes, whilst simultaneously reducing Organ at Risk (OAR) dose; i.e. an improvement of the therapeutic index. This dosimetric improvement translates into clinical benefits; especially in terms of reduced radiotherapy toxicity and Quality of Life. Whilst IMRT may deliver highly conformal, high dose Radiation Therapy (RT); morphological variations in normal tissue and tumour anatomy occur during the course of RT. These variations can result in inadequate dose delivery, requiring reoptimisation of the IMRT plan. Adaptive Radiation Therapy (ART) is an approach whereby the treatment plan is modified to account for
Prostate cancer cells home to bone in a new in vivo model of bone metastasis

This study aimed to establish the dorsal skinfold chamber (DSC) model of prostate cancer metastasis. Metatarsals from newborn mice are engrafted into a DSC implanted a SCID mouse (5‐6 weeks old). We have demonstrated that metatarsals are rapidly vascularised by inosculation with the host vasculature by day 5‐7, with functional vessels by day 2. Vascular density was measured over a 7 day period; day 3, 455 ± 186 cm/cm2; day 5, 546 ± 305 cm/cm2 and day 7, 707 ± 370 cm/cm2. Following this fluorescently labelled prostate (PC3‐GFP) or oral (SCC4‐GFP) cancer cells (1 x 105) are injected via the heart to simulate metastatic spread. Cells initially adhere to the microvascular endothelium and/or to metatarsal matrix 5 days after injection (10 ± 7 cells/metatarsal). Bone viability has been assessed throughout the 4 week study duration and demonstrates viable tissue within the DSC. Histology of the metatarsal confirms the presence of tumour cells, viability of the metatarsal, active growth plate and new vessels formation. This model will allow homing, interactions and extravasation between the tumour and bone microenvironment to be studied in detail. Funded by Sixth European Framework Programme (PROMET).
Genome‐wide association study identifies an early onset pancreatic cancer risk locus

Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore, we performed a genome‐wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I‐II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1 × 10−4). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset ≤50, and 4142 controls from the PANDoRA consortium while in the in silico data, we observed no statistically significant association. However, the resulting meta‐analysis supported the association (P = 1.15 × 10−4). In conclusion, we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature.
Soft Tissue Cephalometric Standards for a Moroccan Teenage Population

The orthodontic treatment aims the restoration of stable and functional occlusion as well as harmonious skeletal proportions in a balanced face. Thus, the orthodontist must give similar attention to the facial or profile soft tissues, the maxillary and mandibular bone bases, and the dento-dental ratios. Soft tissue analysis is an integral part of the facial examination and constitutes a major decision-making element which is as important as the cephalometric dento-skeletal analysis during the setting of the diagnosis and orthodontic treatment plan [1, 2]. The naso-labial angle, the thickness of the lips, and the anteroposterior and vertical position of the chin are all elements that must be taken into consideration to establish the treatment plan.
Spatial architecture of tumour-infiltrating lymphocytes as a prognostic parameter in resected non-small-cell lung cancer.

OBJECTIVES Tumour-infiltrating lymphocytes (TILs) are critically implicated in the clinical outcome and response to immunotherapy in non-small-cell lung cancer (NSCLC) patients. The functional competence of lymphocyte subpopulations is strongly conditioned by their spatial arrangement within the tumour immune microenvironment. The aim of this study was to determine whether the tissue localization of specific TIL subpopulations might have an impact on the risk of recurrence in surgically resected NSCLC. METHODS High-speed scanning of whole slide images was performed on immunohistochemically stained tissue sections from 97 NSCLC patients to assess the number and ratio of CD3+, CD8+ and PD-1+ T-lymphocytes. TIL distribution was computed considering the intratumoural (proximal or distal) and peripheral (invasive margin) localization as well as their location within the fibrotic tissue (immune excluded). The tumour proliferative index was assessed by Ki67 labelling. The impact of TILs number and distribution on clinical-pathological characteristics and outcomes were statistically analysed. RESULTS High density and percentage of proximal CD8+ TILs and low PD-1-to-CD8 ratio had a positive impact on disease-free-survival (P = 0.03) and overall survival (P = 0.003). An inverse correlation was observed between the abundance of intratumoural CD8+ TILs carrying PD-1 inhibitory receptor and cancer cell proliferation. Cases with high compared to low fraction of immune excluded CD8+ TILs had significantly reduced 5-year overall survival (n events: 22 vs 12; P = 0.04) and disease-free survival (n events: 24 vs 16; P = 0.03) rates while the amount of CD3+ and CD8+ TILs located at the invasive margin had a favourable effect on the clinical course. CONCLUSIONS Mapping TIL subpopulations may implement the definition of prognostic parameters in surgically resected NSCLC.
Prognostic role of metastatic lymph node number and lymph node ratio in ampullary adenocarcinoma

Background: The role of the metastatic-to-resected lymph nodes ratio (LNR) and the metastatic lymph node number (LNN) in the staging of ampullary carcinoma (AC) is controversial. This retrospective study evaluates the impact on survival of LNN and LNR in resected AC. Methods: One-hundred patients who underwent pancreaticoduodenectomy with standard lymphadenectomy for AC were categorized into N1 (1-2 metastatic LNs) or N2 (≥3 metastatic LNs) and into LNR ≤0.056 or LNR>0.056 groups. Kaplan-Meier survival curves and multivariate analysis of prognostic factors were assessed. Results: Median overall survival was 90, 36 and 36 for N0, N1 and N2 (p=0.014) and 85 and 35 months for LNR≤0.056 and LNR>0.056 (p=0.006). Median DFS was Not Reached (NR), 33 and 13 months for N0, N1 and N2 (p<0.001), and NR and 17 months for LNR≤0.056 LNR>0.056 (p<0.001). Independent prognostic factors were LNR>0.056 (HR 1.99; p=0.029), R1 margins (HR 2.4; p=0.042) and adjuvant chemotherapy (HR 1.76; p=0.044) for OS; LNN (HR 3.03 and 5.03 for N1 and N2; p=0.003), LNR>0.056 (HR 2.07; p=0.048), and tumor size ≥2cm (HR 2.73; p=0.018) for DFS. Conclusions: Both LNR>0.056 and increasing LNN (1-2 and ≥3) should be considered in the staging of AC, as they are independent predictors of worse prognosis.
Keep Taking Your ACE Inhibitors and ARBs During the COVID 19 Pandemic

ACE2-mediated Co-administration losartan the ACE2 ACE2-mediated metabolism of 125 I-angiotensin II. Measurement of enzymatic activity used a very low substrate concentration, <10 nmolar, which could indicate an altered Km of the ACE2 for its substrate, versus an increase in ACE2 protein.
Effects of swimming and water walking on body composition and spirometric values in young children

Aquatic activities have been recommended as frequent practices due to the physical properties of water with improvements in body composition of young. Objective: To study if there are differences in body composition and spirometric values in children who practice swimming complemented with water walking and those who only practice swimming. Methodology: 28 individuals (6 to 12 years) were divided into two groups: swimming group (SG: n=9) and swimming complemented with water walking group (SWWG: n=19) in three different moments with 6 weeks between them. For body composition a bio-impedance scale was used and an anthropometric tape for the waist circumference. For spirometric values: forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and even peak expiratory flow (PEF) a Cosmed Microquark spirometer was used. For statistical procedures the SPSS (20.0) program for descriptive statistics, the Shapiro Wilk test for testing the normality, inferential statistics (non-parametric Mann-Whitney tests, Friedman's Anova), and for the effect size the d-Cohen test. Results: Regarding the inter-group analysis (comparison between the SG and SWWG) we observed that there were significant differences in weight (p=0,004), forced expiratory volume in 1 second (FEV1: p=0,025) and peak expiratory flow (PEF: p=0,033). Concerning intra-group differences (improvements in the SG and SWWG), the SWWG showed significant improvements in weight muscle mass (p=0,029), fat mass (p=0,002), percentage of water (p=0,018),, body mass index (BMI: p=0,000), body percentiles (p=0,000), forced vital capacity (FVC: p=0,003) and forced expiratory volume in 1 second (FEV1: p=0,008). We have concluded that the practice of swimming and water walking have benefits with differences in the analysed group variables, however, the two activities complemented (swimming and water walking) present improvements much more significant.
A clinical study of gastric outlet obstruction

Background: Gastric outlet obstruction (GOO) is a diagnostic and therapeutic challenge in developing countries to a Surgeon. Gastric outlet obstruction, a clinical condition impeding emptying of stomach mechanically, can be due to varied etiology. This study was taken up to know the etiological factors and management.Methods: This was a descriptive prospective study done at Madurai Medical College for a period of 2 years from September 2009 to August 2011. A set of inclusion and exclusion criteria were defined and followed. Upper gastro-intestinal endoscopy (OGD) was done in all cases while Barium meal study was done in few cases to make the diagnosis. Relevant operative procedure was done, and patients were managed post operatively.Results: Cicatrised Duodenal ulcer (DU) was the commonest cause followed by Carcinoma Pyloric antrum (Ca PA). Majority of the patients were males (67.5%) with male to female ratio of 2.07:1. Vomiting was one of the major presenting symptoms in all the patients.Conclusions: Cicatrised DU was the commonest cause for GOO in present study. Present study highlights the increasing incidence of Ca PA. This could be due to better management of DU at an early stage.
Pulmonary Effects of Passive Smoking Among Adults

Passive smoking, also known as environmental tobacco smoke (ETS) or second-hand smoke (SHS) represents the involuntary inhaling of tobacco released by others in the ambient air. Passive smoking exposure occurs in homes, workplaces, and in other public places such as bars, restaurants, and recreation venues. It consists of a complex mixture of mainstream smoke exhaled by smokers and the smoke given off by the combustion of tobacco products. Non-smokers, being exposed to the same toxic substances as identified in mainstream tobacco smoke are, therefore, at an increased risk for serious adverse health effects. Although attention has centered mainly on the harmful effects of SHS exposure in the pediatric population, epidemiologic data from the last 20 years showed increased risks on various respiratory pathologies of the adult. Inhaling SHS causes injury to the respiratory tract, resulting in a high prevalence of respiratory symptoms, asthma, impairment of lung function and increased bronchial responsiveness. In adults, passive smoking is also associated with an increased risk of lung cancer, especially in those with high exposure. On the basis of recent publications, we propose a review of history, biologic basis and effects on different respiratory pathologies of the exposure to SHS in adults.
Utilization of Melaleuca leucadendron Essential Oil

The chemical composition, antioxidant, antifungal, and physiological effects of commercial Melaleuca leucadendron LINN. (Kayu Putih) oil from Sukun, East Java, Indonesia was investigated in this study. GC-MS analysis showed the majority compounds of this oil are mixtures of monoterpenes and sesquiterpenes, which 1,8-cineole (53.90%) was the most abundant compound in this oil. In vitro antioxidant assay showed this essential oil possessed antioxidant activity (IC50: 4.24mg/ml). In vitro antifungal assay showed relatively strong antifungal activity of this oil against plant pathogenic fungi of F. oxysporum (IC50: 0.44 mg/ml), T. cucumeris (IC50: 0.97mg/ml) and R. oryzae (IC50: 7.71mg/ml). The investigation on the effect of the odor of M. leucadendron oil in this study also showed functional fragrance of this oil for human physiological behavior controlling.
Evaluating the TOSREC as a Brief RTI Screen for Early Struggling Readers in Urban Schools

Efficient response-to-intervention (RTI) screening is critical in urban schools where 60-80% of students read below grade-level. We evaluated the classification validity of the Test of Silent Reading Efficiency and Comprehension (TOSREC) in identifying students receiving school services using two first-grade cohorts in the same urban school. TOSREC slightly underidentified students receiving school interventions; however, most “under-identified” students did not receive interventions for reading problems. TOSREC accurately identified those not-at-risk, but over-identified students who were receiving our research-based reading intervention while waiting for school services. Results suggest that schools need sufficient resources to provide appropriate services for all students needing intervention.
YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators

The N6-methyladenosine (m6A) modification regulates mRNA stability and translation. Here, we show that transcriptomic m6A modification can be dynamic and the m6A reader protein YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) promotes mRNA decay during cell cycle. Depletion of YTHDF2 in HeLa cells leads to the delay of mitotic entry due to overaccumulation of negative regulators of cell cycle such as Wee1-like protein kinase (WEE1). We demonstrate that WEE1 transcripts contain m6A modification, which promotes their decay through YTHDF2. Moreover, we found that YTHDF2 protein stability is dependent on cyclin-dependent kinase 1 (CDK1) activity. Thus, CDK1, YTHDF2, and WEE1 form a feedforward regulatory loop to promote mitotic entry. We further identified Cullin 1 (CUL1), Cullin 4A (CUL4A), damaged DNA-binding protein 1 (DDB1), and S-phase kinase-associated protein 2 (SKP2) as components of E3 ubiquitin ligase complexes that mediate YTHDF2 proteolysis. Our study provides insights into how cell cycle mediators modulate transcriptomic m6A modification, which in turn regulates the cell cycle.
Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8+ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results

Purpose: In oropharyngeal squamous cell carcinoma (OPC), high CD8+ tumor-infiltrating lymphocyte (CD8+TIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab + tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8+TIL density, safety, and efficacy in patients with OPC. Patients and Methods: Patients with newly diagnosed stage II–IVA OPC or locoregionally recurrent OPC amenable to resection were included. Patients were randomized to two cycles of durvalumab or durvalumab + tremelimumab before surgery. The primary endpoint was change between baseline and resection specimen in CD8+TIL density between arms. Secondary endpoints included safety, response rate per RECIST, major pathologic response (MPR; ≤10% viable tumor cells) rate, and patient-reported outcomes. Results: Of 28 eligible patients (14/arm), 20 (71%) had newly diagnosed OPC, and 24 (86%) were p16-positive. The posttreatment to pretreatment median CD8+TIL density ratio was 1.31 for durvalumab and 1.15 for combination treatment (P = 0.97; 95% CI: −1.07–2.28). In each group, 6 patients (43%, 95% CI: 17.66–71.14) had a response. Eight patients (29%) had a MPR at the primary tumor and/or nodal metastases. Neither baseline CD8+TIL density nor PD-L1 expression level correlated with overall response, but a trend toward greater CD8+TIL change in patients with a MPR was seen (P = 0.059; 95% CI: −0.33–3.46). Four patients (14%) had grade ≥3 adverse events. At median follow-up time of 15.79 months, all patients were alive, and one had an additional recurrence. Conclusions: Durvalumab + tremelimumab did not increase CD8+TIL density more than durvalumab alone did. The observed safety and activity support further investigation of neoadjuvant checkpoint inhibitor for OPC.