Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational fluid dynamics of the right atrium: Assessment of modelling criteria for the evaluation of dialysis catheters

Central venous catheters are widely used in haemodialysis therapy, having to respect design requirements for appropriate performance. These are placed within the right atrium (RA); however, there is no prior computational study assessing different catheter designs while mimicking their native environment. Here, a computational fluid dynamics model of the RA, based on realistic geometry and transient physiological boundary conditions, was developed and validated. Symmetric, split and step catheter designs were virtually placed in the RA and their performance was evaluated by: assessing their interaction with the RA haemodynamic environment through prediction of flow vorticity and wall shear stress (WSS) magnitudes (1); and quantifying recirculation and tip shear stress (2). Haemodynamic predictions from our RA model showed good agreement with the literature. Catheter placement in the RA increased average vorticity, which could indicate alterations of normal blood flow, and altered WSS magnitudes and distribution, which could indicate changes in tissue mechanical properties. All designs had recirculation and elevated shear stress values, which can induce platelet activation and subsequently thrombosis. The symmetric design, however, had the lowest associated values (best performance), while step design catheters working in reverse mode were associated with worsened performance. Different tip placements also impacted on catheter performance. Our findings suggest that using a realistically anatomical RA model to study catheter performance and interaction with the haemodynamic environment is crucial, and that care needs to be given to correct tip placement within the RA for improved recirculation percentages and diminished shear stress values.
Clinical and Esophagogastroduodenoscopy Findings in Pediatric Patients With Severe Obesity Evaluated Before Bariatric Surgery

ABSTRACT Objectives: Severe obesity in the pediatric population has lifelong consequences. Bariatric surgery has been suggested for selected adolescents with severe obesity after careful evaluation. The indications for preoperative esophagogastroduodenoscopy (EGD) in this age group are not clear, despite its established usefulness in adults. We aimed to assess the usefulness of EGD before bariatric surgery in pediatric patients with severe obesity and metabolic comorbidities. Methods: We conducted a retrospective chart review in a single tertiary pediatric medical center of adolescents treated during 2011 to 2018. Data collected from electronic medical records included patient demographics, endoscopic findings, and laboratory parameters. Results: A total of 80 patients (40 boys) underwent evaluation. Macroscopic abnormalities were detected in 54% of the endoscopies, including gastritis, esophagitis, and duodenitis in 46%, 16%, and 13%, respectively. Forty-nine percentage of the biopsies showed histological abnormalities; in 35 (44%) patients, Helicobacter pylori was detected. Thirty-three patients (41%) received medical treatment and 2 (2.5%) required a second EGD. Metabolic comorbidities included hypertriglyceridemia (38% of the patients), low high-density lipoprotein (23%), and prediabetic (16%) or diabetic levels of HbA1C (4%). Fifty-five percentage of the cohort had elevated alanine aminotransferase (ALT), suggestive of nonalcoholic fatty liver disease (NAFLD). Conclusions: Endoscopies performed before bariatric surgeries suggest a higher prevalence of clinically significant findings, many of which required treatment. These findings support incorporating an EGD into the preoperative evaluation of this patient population.
Frequency of Parkinsonism and Parkinson Disease in African Americans in the Chicago Community.

BACKGROUND There is paucity of data about African American (AA) patients with Parkinson's disease (PD) and parkinsonism which may precede PD in older adults. Prior studies suggest that there are lower rates of PD in the AA population, with more cognitive impairment in AA with PD. This study aimed to investigate differences in PD, parkinsonism, and cognition between white and AA populations in three longitudinal epidemiologic cohort studies of aging. METHODS This study examined parkinsonism, PD frequency, and cognition of community dwelling older individuals in three longitudinal epidemiologic cohort studies. Parkinsonism was based on an exam utilizing the modified Unified Parkinson's Disease Rating Scale (UPDRS) performed by a nurse. PD was based on self-report, medications used for treatment of PD, and examination findings. Cognition was assessed using 19 performance-based tests that assess five cognitive domains. RESULTS AA subjects were less likely to have parkinsonism compared to whites, even with age and gender differences. Frequency of PD was not significant between groups. AA were more likely to have lower cognitive scores as compared to whites. AA were less likely to have parkinsonism even with controlling for cognitive differences between groups. CONCLUSIONS Parkinsonian signs are present among AAs in the community at lower rates than in white individuals. Cognitive profiles of AA and whites with parkinsonism may be different, suggesting differing contributions of pathology to cognitive decline and parkinsonism between groups. Additional research is needed to understand the progression of parkinsonism to PD, as well as to understanding the cognitive differences in AA with parkinsonism.
Deciphering microRNA-mRNA regulatory network in adult T-cell leukemia/lymphoma; the battle between oncogenes and anti-oncogenes

Adult T-cell leukemia/lymphoma (ATLL) is virus-caused cancer that originates from the infection by human T-cell leukemia virus type 1. ATLL dysregulates various biological pathways related to the viral infection and cancer progression through the dysexpression of miRNAs and mRNAs. In this study, the potential regulatory subnetworks were constructed aiming to shed light on the pathogenesis mechanism of ATLL. For this purpose, two mRNA and one miRNA expression datasets were firstly downloaded from the GEO database. Next, the differentially expressed genes and miRNAs (DEGs and DE-miRNAs, respectively), as well as differentially co-expressed gene pairs (DCGs), were determined. Afterward, common DEGs and DCGs targeted by experimentally validated DE-miRNAs were explored. The oncogenic and anti-oncogenic miRNA-mRNA regulatory subnetworks were then generated. The expression levels of four genes and two miRNAs were examined in the blood samples by qRT-PCR. The members of three oncogenic/anti-oncogenic subnetworks were generally enriched in immune, virus, and cancer-related pathways. Among them, FZD6, THBS4, SIRT1, CPNE3, miR-142-3p, and miR-451a were further validated by real-time PCR. The significant up-regulation of FZD6, THBS4, and miR-451a as well as down-regulation of CPNE3, SIRT1, and miR-142-3p were found in ATLL samples than normal samples. The identified oncogenic/anti-oncogenic subnetworks are pieces of the pathogenesis puzzle of ATLL. The ultimate winner is probably an oncogenic network that determines the final fate of the disease. The identified genes and miRNAs are proposed as novel prognostic biomarkers for ATLL.
Impact of Metronidazole Treatment and Dientamoeba Fragilis Colonization on Gut Microbiota Diversity

Supplemental Digital Content is available in the text ABSTRACT Objectives: The intestinal parasite Dientamoeba fragilis is a common colonizer of children in Denmark. Metronidazole has been used to reduce gastrointestinal symptoms in children colonized with D fragilis. We aimed to identify gut microbiota changes associated with D fragilis carrier status and metronidazole treatment of D fragilis-positive children. Methods: The fecal microbiota of 275 fecal samples from children treated with metronidazole (n = 48) or placebo (n = 48) were characterized by ribosomal DNA sequencing. Samples collected before (T1), 2 weeks after (T2), and 8 weeks (T5) after treatment were included. Seventy fecal samples from 70 age-matched parasite-negative children served as controls. Results: The abundance of 24 bacterial genera differed significantly according to D fragilis carrier status, with Flavonifractor being remarkably more abundant in children testing negative for D fragilis. Eight bacterial genera changed significantly in abundance in children losing versus keeping D fragilis after metronidazole treatment. Of these, 7 returned to pretreatment (T1) levels at T5. Meanwhile, the abundance of Flavonifractor continued to differ at T5, whereas for Ruminococcus the abundance only remained high in children who were D fragilis-negative at T2 and T5. Increases in Hungatella, Sutterella, and Streptococcus abundances observed at T2 were specific to metronidazole exposure and hence independent of D fragilis colonization. Conclusions: This study revealed that specific bacterial genera were associated with D fragilis colonization. Metronidazole treatment had a short-term impact on the abundance of some bacterial genera, with most of these reverting to pretreatment levels 8 weeks after completed treatment.
Inhaled fixed-dose combination powders for the treatment of respiratory infections

ABSTRACT Introduction Respiratory infections are a major cause of morbidity and mortality. As an alternative to systemic drug administration, inhaled drug delivery can produce high drug concentrations in the lung tissue to overcome resistant bacteria. The development of inhaled fixed-dose combination powders (I-FDCs) is promising next step in this field, as it would enable simultaneous drug-drug or drug-adjuvant delivery at the site of infection, thereby promoting synergistic activity and improving patient compliance. Areas covered This review covers the clinical and pharmaceutical rationales for the development of I-FDCs for the treatment of respiratory infections, relevant technologies for particle and powder generation, and obstacles which must be addressed to achieve regulatory approval. Expert opinion I-FDCs have been widely successful in the treatment of asthma and chronic obstructive pulmonary disease; however, application of I-FDCs towards the treatment of respiratory infections carries additional challenges related to the high dose requirements and physicochemical characteristics of anti-infective drugs. At present, co-spray drying is an especially promising approach for the development of composite fixed-dose anti-infective particles for inhalation. Though the majority of fixed-dose research has thus far focused on the combination of multiple antibiotics, future work may shift to the additional inclusion of immunomodulatory agents or repurposed non-antibiotics.
Grandchildren’s food workshop: Impact of an intergenerational cooking program on dietary habits, food courage, cooking skills and two-way interaction in Danish children and their grandparents

Background: Good nutrition is a key aspect of health. Cooking activities can improve dietary habits, cooking skills and food courage in terms of courage to cook and taste new foods, in individuals of all ages. However, targeting both grandchildren and grandparents at the same time through intergenerational cooking activities, is new. Aim: This paper aims to present the impact of intergenerational cooking activities on dietary habits, food courage, cooking skills and two-way interaction between young and old participants in The Grandchildren’s Food Workshop. Methods: In this observational pilot study, the Danish Heart Foundation’s experimental cooking program for grandchildren and grandparents was developed and tested. The influence of the food workshop on the participants’ dietary habits, food courage, cooking skills and two-way interaction was assessed by a before and after questionnaire. McNemar’s and chi-squared tests were used to evaluate the effects. Results: A total of 180 grandchildren (10 to 12 years) and 183 grandparents participated in The Grandchildren’s Food Workshop. A total of 82 (46%) grandchildren (71% of which were girls) and 125 (68%) grandparents (83% of which were women) responded to the baseline and follow-up questionnaires. The impact on dietary habits and food courage was limited, while there was an impact on cooking skills in the grandchildren. The already good two-way interaction was unaltered. Conclusions: The findings indicate an impact on cooking skills among grandchildren participating in The Grandchildren’s Food Workshop, while the impact on dietary habits, food courage and two-way interaction between age groups was limited. Further research, including more detailed dietary data, should explore the significance of an intergenerational approach.
A systematic literature review of schistosomiasis in urban and peri-urban settings

Background Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and belongs to the neglected tropical diseases. The disease has been reported in 78 countries, with around 290.8 million people in need of treatment in 2018. Schistosomiasis is predominantly considered a rural disease with a subsequent focus of research and control activities in rural settings. Over the past decades, occurrence and even expansion of schistosomiasis foci in peri-urban and urban settings have increasingly been observed. Rural–urban migration in low- and middle-income countries and subsequent rapid and unplanned urbanization are thought to explain these observations. Fifty-five percent (55%) of the world population is already estimated to live in urban areas, with a projected increase to 68% by 2050. In light of rapid urbanization and the efforts to control morbidity and ultimately achieve elimination of schistosomiasis, it is important to deepen our understanding of the occurrence, prevalence, and transmission of schistosomiasis in urban and peri-urban settings. A systematic literature review looking at urban and peri-urban schistosomiasis was therefore carried out as a first step to address the research and mapping gap. Methodology Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic computer-aided literature review was carried out using PubMed, ScienceDirect, and the World Health Organization Database in November 2019, which was updated in March 2020. Only papers for which at least the abstract was available in English were used. Relevant publications were screened, duplicates were removed, guidelines for eligibility were applied, and eligible studies were reviewed. Studies looking at human Schistosoma infections, prevalence, and intensity of infection in urban and peri-urban settings were included as well as those focusing on the intermediate host snails. Principal findings A total of 248 publications met the inclusion criteria. The selected studies confirm that schistosomiasis is prevalent in peri-urban and urban areas in the countries assessed. Earlier studies report higher prevalence levels in urban settings compared to data extracted from more recent publications, yet the challenge of migration, rapid uncontrolled urbanization, and resulting poor living conditions highlight the potential for continuous or even newly established transmission to take place. Conclusions The review indicates that schistosomiasis has long existed in urban and peri-urban areas and remains a public health problem. There is, however, a challenge of comparability of settings due to the lack of a clear definition of what constitutes urban and peri-urban. There is a pressing need for improved monitoring of schistosomiasis in urban communities and consideration of treatment strategies.
Bacterial-driven inflammation and mutant BRAF expression combine to promote murine colon tumorigenesis that is sensitive to immune checkpoint therapy.

Colorectal cancer (CRC) is multi-faceted with subtypes defined by genetic, histological, and immunologic features which are potentially influenced by inflammation, mutagens, and/or microbiota. CRCs with activating mutations in BRAF are associated with distinct clinical characteristics though the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (MinApc[triangle]716/+) enterotoxigenic Bacteroides fragilis (ETBF) murine model is characterized by IL-17-dependent, distal colon adenomas. Herein, we report that addition of the BRAFV600E mutation to this model results in emergence of a distinct locus of mid-colon tumors. In ETBF-colonized BRAFV600ELgr5CreMin (BLM) mice, tumors have similarities to human BRAFV600E tumors, including histology, CpG island DNA hypermethylation, and immune signatures. In comparison to Min ETBF tumors, BLM ETBF tumors are infiltrated by CD8+ T cells, express interferon-gamma signatures, and are sensitive to anti-PDL1 treatment. These results provide direct evidence for critical roles of host genetic and microbiota interactions in CRC pathogenesis and sensitivity to immunotherapy.
Anosmia in the first coronavirus disease 2019 outbreak in Europe: functional recovery after eight months

Abstract Background Severe acute respiratory syndrome coronavirus-2 is a formidable virus, responsible for coronavirus disease 2019 and endowed with marked neurotropism. The damage it causes to the nervous system is manifold. The main neurological manifestation is anosmia. Olfactory damage is often transient, but there are no data reflecting an observational period of several months. Objective This study evaluated the trend of anosmia in patients affected by coronavirus disease 2019 in the eight months following diagnosis. Methods Fifty-five subjects who presented with symptoms suggestive of coronavirus disease 2019 and who developed anosmia, between the end of February and the beginning of March 2020, were investigated. The patients were interviewed after eight months to determine functional recovery and assess the degree of recovery. Results Ninety-one per cent of the population reported olfactory recovery and, of these, 53 per cent had total recovery after eight months. Females and younger age groups seem slightly advantaged in functional recovery. The elderly population appears to have excellent prospects for full functional recovery. Conclusion Anosmia represents a frequent neurological manifestation during coronavirus disease 2019. Fortunately, it is transient in most cases, and only a small percentage of patients affected by it report long-term functional deficits.
Visfatin: An emerging adipocytokine bridging the gap in the evolution of cardiovascular diseases

Visfatin/nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine expressed predominately in visceral fat tissues. High circulating levels of visfatin/NAMPT have been implicated in vascular remodeling, vascular inflammation, and atherosclerosis, all of which pose increased risks of cardiovascular events. In this context, increased levels of visfatin have been correlated with several upregulated pro‐inflammatory mediators, such as IL‐1, IL‐1Ra, IL‐6, IL‐8, and TNF‐α. Furthermore, visfatin is associated with leukocyte recruitment by endothelial cells and the production of adhesion molecules such as vascular cell adhesion molecule 1, intercellular cell adhesion molecule 1, and E‐selectin, which are well known to mediate the progression of atherosclerosis. Moreover, diverse angiogenic factors have been found to mediate visfatin‐induced angiogenesis. These include matrix metalloproteinases, vascular endothelial growth factor, monocyte chemoattractant protein 1, and fibroblast growth factor 2. This review aims to provide a comprehensive overview of the pro‐inflammatory and angiogenic actions of visfatin, with a focus on the pertinent signaling pathways whose dysregulation contributes to the pathogenesis of atherosclerosis. Most importantly, some hypotheses regarding the integration of the aforementioned factors with the plausible atherogenic effect of visfatin are put forth for consideration in future studies. The pharmacotherapeutic potential of modulating visfatin's roles could be important in the management of cardiovascular disease, which continues to be the leading cause of death worldwide.
Genetic Analysis of Korean Adult Patients with Nontuberculous Mycobacteria Suspected of Primary Ciliary Dyskinesia Using Whole Exome Sequencing

Purpose Nontuberculous mycobacteria (NTM) is ubiquitous in the environment, but NTM lung disease (NTM-LD) is uncommon. Since exposure to NTM is inevitable, patients who develop NTM-LD are likely to have specific susceptibility factors, such as primary ciliary dyskinesia (PCD). PCD is a genetically heterogeneous disorder of motile cilia and is characterized by chronic respiratory tract infection, organ laterality defect, and infertility. In this study, we performed whole exome sequencing (WES) and investigated the genetic characteristics of adult NTM patients with suspected PCD. Materials and Methods WES was performed in 13 NTM-LD patients who were suspected of having PCD by clinical symptoms and/or ultrastructural ciliary defect observed by transmission electron microscopy. A total of 45 PCD-causing genes, 23 PCD-candidate genes, and 990 ciliome genes were analyzed. Results Four patients were found to have biallelic loss-of-function (LoF) variants in the following PCD-causing genes: CCDC114, DNAH5, HYDIN, and NME5. In four other patients, only one LoF variant was identified, while the remaining five patients did not have any LoF variants. Conclusion At least 30.8% of NTM-LD patients who were suspected of having PCD had biallelic LoF variants, and an additional 30.8% of patients had one LoF variant. Therefore, PCD should be considered in patients with NTM-LD with symptoms or signs suspicious of PCD.
Clinical Predictors of Morbidity and Mortality in Hospitalized Pediatric Patients With Ascites

Supplemental Digital Content is available in the text ABSTRACT Objectives: Ascites is a pathologic buildup of fluid in the peritoneal cavity. Knowledge is lacking in clinical outcome in pediatric patients with ascites. We aim to identify and assess clinical variables, associated with morbidity and mortality in pediatric patients who are hospitalized with ascites. Methods: A retrospective cohort study was performed on patients ages 0 to 21 hospitalized at Johns Hopkins Hospital between 1983 and 2010 with an ICD-9 discharge diagnosis of ascites (789.5, 789.51, 789.59). A total of 518 pediatric patients were studied, all with a diagnosis of ascites during hospitalization. Study outcomes included hospital length of stay (LOS) as a proxy for morbidity and death at hospital discharge for mortality. Variables analyzed included demographic data, ascites etiology and grade, comorbidities, and laboratory markers. Variables were analyzed by log-linear regression and competing risk model. Results: Among the 3 age groups (0–5, 6–12, and 13–21), the 0 to 5 age group experienced significantly increased LOS (P < 0.001) and mortality (P = 0.027). Ascites etiology of veno-occlusive disease (VOD) and the presence of hydrothorax or thrombocytopenia was also significantly associated with increased LOS. Ascites with the etiology of congestive hepatopathy and the presence of grade 3 ascites, hepatic encephalopathy, hepatorenal syndrome, hydrothorax, hyponatremia, and thrombocytopenia were associated with increased mortality. Additionally, black pediatric patients have an increased risk of mortality (P = 0.027). Other factors including sex, leukopenia, portal vein thrombosis, and splenomegaly were not associated with LOS or mortality. Conclusions: Morbidity and mortality in pediatric patients hospitalized with ascites are associated with specific demographic and clinical factors. Further studies are required to apply this knowledge to predict the clinical outcomes.