Miracle-dz/UniFAR-FTUs huggingface dataset:
A Study to Assess The Correlation Between Cardiac Magnetic Resonance Imaging (CMR), Echocardiography and, When Available, Right Heart Catheterisation in The Evaluation of Pulmonary Arterial Pressure

OBJECTIVES : Cardiac Magnetic Resonance imaging (CMR) is an accurate tool for the evaluation of the right ventricular mass, volume and function. We studied the accuracy of CMR when compared to Echocardiography and, when available, right heart catheterisation, in the measurement of pulmonary arterial pressures in patients with clinically suspected pulmonary hypertension, who underwent imaging or when pulmonary hypertension was suspected on cardiac MRI using quantitative parameters. We also studied the correlation between various parameters in CMR to pulmonary arterial pressures measured on Echocardiography and right heart catheterisation. Additionally, we describe and characterise the various CMR imaging features seen in the subset of our subjects with pulmonary hypertension diagnosed on Echocardiography qualitatively. METHODS : We prospectively studied 20 consecutive subjects with suspected or diagnosed pulmonary hypertension who underwent both echocardiography and cardiac magnetic resonance imaging including 6 subjects who underwent right heart catheterisation (RHC). Correlation of multiple CMR measurements with mean pulmonary arterial pressures (mPAP) measured on echocardiography was assessed using Pearson’s Linear Correlation coefficient and significance was determined using p value. RESULTS : Ventricular mass index (VMI) and ratio of the diameter of the main pulmonary artery to that of the ascending aorta at the same level were the CMR measurements with the strongest correlation with mPAP (p < 0.001). Other parameters related to right ventricular mass and motion of the interverntricular septum also showed significant correlation. CONCLUSION : CMR is a versatile tool in the assessment of parameters that indicate right heart status and function which correlate well with measurement of mean pulmonary arterial pressures on Echocardiography and therefore may be used to diagnose and prognosticate pulmonary hypertension. Routine measurement of ventricular mass index and systolic eccentricity index of the left ventricle is recommended in patients suspected with or diagnosed to have pulmonary hypertension who undergo cardiac magnetic resonance imaging.
Effect of different biopolymer-based structured systems on the survival of probiotic strains during storage and in vitro digestion.

BACKGROUND This study aimed at evaluating the protective effect of different biopolymer systems on the viability of two probiotics (Lactobacillus rhamnosus and Streptococcus thermophilus) during storage and in vitro digestion. Methylcellulose (MC), sodium alginate (SA), and whey protein (WP)-based structures were designed and characterized in terms of pH, rheological properties and visual appearance. RESULTS Results highlighted that the WP-system ensured probiotic protection during both storage and in vitro digestion. This result was attributed to a combined effect of the physical barrier offered by protein gel network and whey proteins as a nutrient for microbes. On the other hand, surprisingly, the viscous methylcellulose-based system was able to guarantee good microbial viability during storage. However, this was not confirmed during in vitro digestion. The reverse results were obtained for sodium alginate beads. CONCLUSION The results acquired suggest that the capacity of a polymeric structure to protect probiotic bacteria is a combination of structure organization and system formulation. This article is protected by copyright. All rights reserved.
Expansion of the Transporter-Opsin-G protein-coupled receptor superfamily with five new protein families

Here we provide bioinformatic evidence that the Organo-Arsenical Exporter (ArsP), Endoplasmic Reticulum Retention Receptor (KDELR), Mitochondrial Pyruvate Carrier (MPC), L-Alanine Exporter (AlaE), and the Lipid-linked Sugar Translocase (LST) protein families are members of the Transporter-Opsin-G Protein-coupled Receptor (TOG) Superfamily. These families share domains homologous to well-established TOG superfamily members, and their topologies of transmembranal segments (TMSs) are compatible with the basic 4-TMS repeat unit characteristic of this Superfamily. These repeat units tend to occur twice in proteins as a result of intragenic duplication events, often with subsequent gain/loss of TMSs in many superfamily members. Transporters within the ArsP family allow microbial pathogens to expel toxic arsenic compounds from the cell. Members of the KDELR family are involved in the selective retrieval of proteins that reside in the endoplasmic reticulum. Proteins of the MPC family are involved in the transport of pyruvate into mitochondria, providing the organelle with a major oxidative fuel. Members of family AlaE excrete L-alanine from the cell. Members of the LST family are involved in the translocation of lipid-linked glucose across the membrane. These five families substantially expand the range of substrates of transport carriers in the superfamily, although KDEL receptors have no known transport function. Clustering of protein sequences reveals the relationships among families, and the resulting tree correlates well with the degrees of sequence similarity documented between families. The analyses and programs developed to detect distant relatedness, provide insights into the structural, functional, and evolutionary relationships that exist between families of the TOG superfamily, and should be of value to many other investigators.
Impact of disease duration and β‐cell reserve on the efficacy of switching to iGlarLixi in adults with type 2 diabetes on glucagon‐like peptide‐1 receptor agonist therapy: Exploratory analyses from the LixiLan‐G trial

Abstract Aim To evaluate the efficacy of iGlarLixi by C‐peptide levels and duration of diabetes in an exploratory analysis of the LixiLan‐G study. Methods LixiLan‐G was a 26‐week, randomized, open‐label study in adults with type diabetes (T2D) inadequately controlled while on a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA), with metformin, with or without pioglitazone and/or a sodium‐glucose co‐transporter‐2 inhibitor. This analysis investigated the efficacy of switching to iGlarLixi by fasting baseline quartile C‐peptide levels and baseline quartile of duration of T2D compared with continued GLP‐1 RA use. Results Change in glycated hemoglobin (HbA1c) from baseline to week 26 was significantly greater with iGlarLixi compared with continued GLP‐1 RAs across all fasting C‐peptide quartiles (−1.00% to −1.06% vs. –0.23% to −0.54% range, respectively) and irrespective of all T2D duration quartiles (−0.94% to −1.07% vs. –0.25% to −0.50% range). A significantly greater proportion of participants in the iGlarLixi arm achieved an HbA1c of <7% across all C‐peptide quartiles (51%‐73% range) than in the GLP‐1 RA arm (19%‐32% range). The greatest reductions in HbA1c in participants receiving iGlarLixi were observed in those with the shortest duration of disease, although consistently greater than reductions observed with continued GLP‐1 RAs. Reductions in HbA1c were comparable across C‐peptide quartiles within the iGlarLixi arm. Conclusions The results of this study suggest that iGlarLixi is an effective treatment option, irrespective of C‐peptide levels or duration of diabetes, in adults with insufficiently controlled T2D receiving GLP‐1 RAs.
A patient-independent CT intensity matching method using conditional generative adversarial networks (cGAN) for single x-ray projection-based tumor localization

A convolutional neural network (CNN)-based tumor localization method with a single x-ray projection was previously developed by us. One finding is that the discrepancy in the discrepancy in the intensity between a digitally reconstructed radiograph (DRR) of a three-dimensional computed tomography (3D-CT) and the measured x-ray projection has an impact on the performance. To address this issue, a patient-dependent intensity matching process for 3D-CT was performed using 3D-cone-beam computed tomography (3D-CBCT) from the same patient, which was sometimes inefficient and could adversely affect the clinical implementation of the framework. To circumvent this, in this work, we propose and validate a patient-independent intensity matching method based on a conditional generative adversarial network (cGAN). A 3D cGAN was trained to approximate the mapping from 3D-CT to 3D-CBCT from previous patient data. By applying the trained network to a new patient, a synthetic 3D-CBCT could be generated without the need to perform an actual CBCT scan on that patient. The DRR of the synthetic 3D-CBCT was subsequently utilized in our CNN-based tumor localization scheme. The method was tested using data from 12 patients with the same imaging parameters. The resulting 3D-CBCT and DRR were compared with real ones to demonstrate the efficacy of the proposed method. The tumor localization errors were also analyzed. The difference between the synthetic and real 3D-CBCT had a median value of no more than 10 HU for all patients. The relative error between the DRR and the measured x-ray projection was less than 4.8% ± 2.0% for all patients. For the three patients with a visible tumor in the x-ray projections, the average tumor localization errors were below 1.7 and 0.9 mm in the superior-inferior and lateral directions, resepectively. A patient-independent CT intensity matching method was developed, based on which accurate tumor localization was achieved. It does not require an actual CBCT scan to be performed before treatment for each patient, therefore making it more efficient in the clinical workflow.
Fusobacterium nucleatum interaction with Pseudomonas aeruginosa induces biofilm-associated antibiotic tolerance via FadA.

Respiratory infection with Pseudomonas aeruginosa or Fusobacterium nucleatum is associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and failure in antibiotic treatment. However, the impact of these dual-species interactions on the severity of COPD and biofilm antibiotic susceptibility remains poorly understood. This study demonstrated that F. nucleatum frequently coexisted with P. aeruginosa in the respiratory tract, and the number of F. nucleatum was negatively correlated with lung function of AECOPD patients. Coculture of P. aeruginosa and F. nucleatum promoted bacterial proliferation, and induced antibiotic tolerance through forming a dense biofilm surrounding by excessive Pel and Psl polysaccharides. Moreover, F. nucleatum adhesin FadA, rather than its spent medium, induced antibiotic tolerance of P. aeruginosa biofilm. These results indicate that F. nucleatum is a biomarker of lung function decline in AECOPD patients, and in vitro interacts with P. aeruginosa to resist antibiotics via FadA, which would be a potential anti-infective target of these dual-species infection.
Adolescent Obesity and Early-Onset Type 2 Diabetes

OBJECTIVE Type 2 diabetes (T2D) is increasingly diagnosed at younger ages. We investigated the association of adolescent obesity with incident T2D at early adulthood. RESEARCH DESIGN AND METHODS A nationwide, population-based study evaluated 1,462,362 adolescents (59% men, mean age 17.4 years) during 1996–2016. Data were linked to the Israeli National Diabetes Registry. Weight and height were measured at study entry. Cox proportional models were applied. RESULTS During 15,810,751 person-years, 2,177 people (69% men) developed T2D (mean age at diagnosis 27 years). There was an interaction among BMI, sex, and incident T2D (Pinteraction = 0.023). In a model adjusted for sociodemographic variables, the hazard ratios for diabetes diagnosis were 1.7 (95% CI 1.4–2.0), 2.8 (2.3–3.5), 5.8 (4.9–6.9), 13.4 (11.5–15.7), and 25.8 (21.0–31.6) among men in the 50th–74th percentile, 75th–84th percentile, overweight, mild obesity, and severe obesity groups, respectively, and 2.2 (1.6–2.9), 3.4 (2.5–4.6), 10.6 (8.3–13.6), 21.1 (16.0–27.8), and 44.7 (32.4–61.5), respectively, in women. An inverse graded relationship was observed between baseline BMI and mean age of T2D diagnosis: 27.8 and 25.9 years among men and women with severe obesity, respectively, and 29.5 and 28.5 years among low-normal BMI (5th–49th percentile; reference), respectively. The projected fractions of adult-onset T2D that were attributed to high BMI (≥85th percentile) at adolescence were 56.9% (53.8–59.9%) and 61.1% (56.8–65.2%) in men and women, respectively. CONCLUSIONS Severe obesity significantly increases the risk for incidence of T2D in early adulthood in both sexes. The rise in adolescent severe obesity is likely to increase diabetes incidence in young adults in coming decades.
Neuroprotective effect of melatonin on radiation‐induced oxidative stress and apoptosis in the brainstem of rats

This study aimed to determine the effects of melatonin on irradiation‐induced apoptosis and oxidative stress in the brainstem region of Wistar rats. Therefore, the animals underwent whole‐brain X‐radiation with a single dose of 25 Gy in the presence or absence of melatonin pretreatment at a concentration of 100 mg/kg BW. The rats were allocated into four groups (10 rats in each group): namely, vehicle control (VC), 100 mg/kg of melatonin alone (MLT), irradiation‐only (RAD), and irradiation plus 100 mg/kg of melatonin (RAM). An hour before irradiation, the animals received intraperitoneal (IP) melatonin and then were killed after 6 hr, followed by measurement of nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and total antioxidant capacity (TAC) in the brainstem region. Furthermore, the western blot analysis technique was performed to assess the caspase‐3 expression level. Results showed significantly higher MDA and NO levels in the brainstem tissues for the RAD group when compared with the VC group (p < .001). Moreover, the irradiated rats exhibited a significant decrease in the levels of CAT, SOD, GPx, and TAC (p < .01, p < .001, p < .001, and p < .001, respectively) in comparison to the VC group. The results of apoptosis assessment revealed that the expression level of caspase‐3 significantly rose in the RAD group in comparison with the VC group (p < .001). Pretreatment with melatonin ameliorated the radiation‐induced adverse effects by decreasing the MDA and NO levels (p < .001) and increasing the antioxidant enzyme activities (p < .001). Consequently, the caspase‐3 protein expression level in the RAM group showed a significant reduction in comparison with the RAD group (p < .001). In conclusion, melatonin approximately showed a capacity for neuroprotective activity in managing irradiation‐induced oxidative stress and apoptosis in the brainstem of rats; however, the use of melatonin as a neuroprotective agent in humans requires further study, particularly clinical trials.
Development of zeaxanthin‐rich tomato fruit through genetic manipulations of carotenoid biosynthesis

Summary The oxygenated carotenoid zeaxanthin provides numerous benefits to human health due to its antioxidant properties. Especially it is linked to protecting, together with the xanthophyll lutein, the retina in the human eye by filtering harmful blue light thus delaying the progression of age‐related macular degeneration (AMD), the most prevalent cause of blindness in developed countries. Despite its high nutritional value, zeaxanthin is less available than other substantial carotenoids in our diet. To solve this shortage, we chose to develop a new food source that would contain a high concentration of natural zeaxanthin. Tomato (Solanum lycopersicum L.) was selected as the target plant since it is the second largest vegetable crop grown worldwide and its fruit characteristically synthesizes and accumulates a high concentration of carotenoids. We employed two genetic approaches in order to enhance zeaxanthin biosynthesis in tomato fruit: a transgenic metabolic engineering and classical genetic breeding. A nontransgenic tomato line, named ‘Xantomato’, was generated whose fruit accumulated zeaxanthin at a concentration of 39 μg/g fresh weight (or 577 μg/g dry weight), which comprised ca. 50% of total fruit carotenoids compared to zero in the wild type. This is the highest concentration of zeaxanthin reached in a primary crop. Xantomato can potentially increase zeaxanthin availability in the human diet and serve as raw material for industrial applications.
Select Epstein-Barr Virus-Associated Digestive Tract Lesions for the Practicing Pathologist.

CONTEXT. — Epstein-Barr virus is a ubiquitous oncogenic virus. During the past 5 decades, the virus has been linked to several disease entities, both neoplastic and nonneoplastic. Several Epstein-Barr virus-associated conditions affect the digestive organs, ranging from mild transient inflammatory conditions to more debilitating and even fatal diseases. OBJECTIVE. — To discuss the clinicopathologic aspects of some newly or recently recognized Epstein-Barr virus-related conditions encountered in the digestive system and their therapeutic implications. DATA SOURCES. — Published peer-reviewed literature was reviewed. CONCLUSIONS. — This article highlights the importance of recognizing the discussed lesions because they influence the direct clinical management or work as a potential predictive marker for therapy.
ORAL CYCLOSPORINE AS AN ALTERNATIVE FOR INITIAL STANDARD PROPHYLAXIS IN ALLOGENEIC STEM CELL TRANSPLANTATION WHEN INTRAVENOUS FORMULATION IS UNAVAILABLE

Objective: The objective of the study was to compare the incidence of acute graft versus host disease (aGVHD) between oral and intravenous (IV) initial standard cyclosporine A (CsA) prophylaxis in a tertiary care center in Mexico.Methods: A total of 117 consecutive patients who underwent allogeneic hematopoietic stem cell transplantations (HSCT) were retrospectively analyzed. GVHD prophylaxis consisted of CsA and methotrexate (MTX). CsA was administered IV, until 2005, when it was withdrawn from the market, and CsA was administered orally.Results: Most of the patients were male (55%), with a median age of 33 years (range, 15–63). 92 patients (79%) received CsA orally, and 25 (22%) intravenously. There were no significant differences in CsA concentrations during weeks 1, 2, 3, and 4 between the oral and IV group. From the entire cohort, 1 patient (4%) from the IV group and 16 (17%) from the oral group developed aGVHD, respectively. Sex, gender disparity, and HSCT source were statistically associated with aGVHD in the multivariate analysis.Conclusions: Using oral instead of IV CsA for aGVHD prophylaxis is feasible and could be financially efficient; nonetheless, our results showed a higher incidence of aGVHD in the oral group; however, our study has limitations and further prospective studies including a larger cohort are encouraged.
Novel agents for mantle cell lymphoma: molecular rational and clinical data

ABSTRACT Introduction Mantle cell lymphoma (MCL) is an aggressive B cell non-Hodgkin lymphoma (NHL) that is characterized by the translocation t(11;14)(q13;q32) and a poor response to rituximab-anthracycline-based chemotherapy. Intensive regimens offer durable response, but a subgroup of MCL patients will not be eligible for those regimens and hence are candidates for less toxic, novel therapies based on a more tailored personalized approach. Areas covered This article examines the molecular landscape of MCL, drug resistance mechanisms, and the data on emerging targeted therapies. Expert opinion DNA damage pathway, ATM mutation, TP53, and epigenetic abnormalities are key drivers of MCL. sBCL2, PARP, ATR, CDK inhibitors or epigenetic modifiers are among the most promising drugs under investigation in clinical trials. The genomic landscape of MCL suggests two types of disease based on the presence of ATM or TP53 alterations which should be the framework of future molecular driven strategies. Among novel drugs, those interacting with the DNA damage response pathway offer the most effective rational for their use in MCL.
Human Papillomavirus Selected Properties And Related Cervical Cancer Prevention Issues.

High-risk Human papillomavirus strains are widely known to be the causative agents responsible for cervical cancer development. Aggregated damage caused by papillomaviruses solely is estimated in at least 5% of all malignancies of the human body and 16% in cancers that affect the female genital area. Enhanced understanding of the complex issue on how the high extent of carcinogenicity is eventually formed due to infection by the Papoviridae family would contribute to enhancing current prevention strategies not only towards cervical cancer, but also other HPV associated cancers. This review article is aimed at presenting the key points in two directions: the current cervical cancer prevention and related aspects of HPV behavior. Virtually all presently applied technologies related to HPV diagnostics and screening programs, such as HPV tests, colposcopy-based tests (VIA/VILI), conventional and liquid-based cytology available in some the most indicative countries are presented. Issues of availability, advantages, and drawbacks of the screening programs, as well as vaccination strategies, are also reviewed in the article based on the analyzed sources. The current point of view regarding HPV is discussed with emphasis on the most problematic aspect of the HPV family concerning the observed increasing number of the highly carcinogenic types. Present trends in HPV infection diagnostics throughout the human fluids and tissues are also reported, including the latest novelties in this field, such as HPV assay/self-sample device combinations. Besides, a brief outline of the related prevention issues in Kazakhstan, the leading country of Central Asia, is presented. Kazakhstan, as one of the postsoviet middle-income countries, may serve as an example of the current situation in those terrains concerning the implementation of globally accepted cervical cancer prevention strategies. Along with positive achievements such as the development of a nationwide screening program, a range of drawbacks is also analyzed and discussed.
Improving Well-Being Among Trainees: A Partnership to Reduce Barriers to Primary Care Services

Background Improved well-being is a focus for graduate medical education (GME) programs. Residents and fellows often express difficulty with visiting primary care physicians, and this issue has not been thoroughly investigated. Objective We reported implementation and utilization of a primary care concierge scheduling service and a primary care video visit service for GME trainees. Methods GME leaders collaborated with Duke Primary Care to offer trainees a concierge scheduling service and opportunity for primary care video visits. This quantitative evaluation included (1) analysis of the institutional GME survey results pre- and post-intervention, and (2) review of use of the concierge scheduling line. Results Comparison of the 2018 and 2019 internal GME surveys showed a decrease in perceived barriers accessing primary care (58% to 31%, P < .0001), a decrease in perceived delays to access primary care (27% to 21%, P = .023), and an increase in respondents who reported needing health care services in the past year (37% to 62%, P < .0001). Although increased need for health services was reported, there was no difference in the proportion reporting use of health services (63% and 65%, P = .43). Of the 142 concierge line calls reviewed, 127 (87%) callers requested clinic appointments, and 15 (10%) callers requested video appointments. Of callers requesting clinic appointments, 99 (80%) were scheduled. Conclusions Providing resources to connect trainees to primary care greatly reduces their perception of barriers to health care and may provide a convenient mechanism to schedule flexible primary care appointments.