Miracle-dz/UniFAR-FTUs huggingface dataset:
Early and Long-Term Outcomes of Surgical Treatment of Ebstein’s Anomaly

Objective This study aimed to evaluate Ebstein’s anomaly surgical correction and its early and long-term outcomes. Methods A retrospective analysis of 62 consecutive patients who underwent surgical repair of Ebstein’s anomaly in our institution from January 2000 to July 2016. The following long-term outcomes were evaluated: survival, reoperations, tricuspid regurgitation, and postoperative right ventricular dysfunction. Results Valve repair was performed in 46 (74.2%) patients - 12 of them using the Da Silva cone reconstruction; tricuspid valve replacement was performed in 11 (17.7%) patients; univentricular palliation in one (1.6%) patient; and the one and a half ventricle repair in four (6.5%) patients. The patients’ mean age at the time of surgery was 20.5±14.9 years, and 46.8% of them were male. The mean follow-up time was 8.8±6 years. The 30-day mortality rate was 8.06% and the one and 10-year survival rates were 91.9% both. Eleven (17.7%) of the 62 patients required late reoperation due to tricuspid regurgitation, in an average time of 7.1±4.9 years after the first procedure. Conclusion In our experience, the long-term results of the surgical treatment of Ebstein's anomaly demonstrate an acceptable survival rate and a low incidence of reinterventions.
Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation

Regorafenib is one option for second‐line treatment of hepatocellular carcinoma (HCC), improving overall survival (OS) of sorafenib‐tolerant patients who develop progression. We aim to evaluate the safety and outcomes of regorafenib as second‐line treatment for HCC recurrence after liver transplantation (LT). This is a retrospective, multicenter, international study including regorafenib‐treated LT patients (2015‐2018), with analysis of baseline characteristics and evolutionary events during sorafenib/regorafenib treatment. Twenty‐eight LT patients (57 years, 7% cirrhotics, 54% performance status 1) were included. Median time from LT to regorafenib initiation was 3.9 (1.1‐18.5) years; median time on sorafenib was 11.3 (0.7‐76.4) months and 14 (1‐591) days from sorafenib discontinuation to regorafenib. During regorafenib (6.3 months), all patients had at least one adverse event (AE), the most common grade 3/4 AEs were fatigue (n = 7) and dermatological reaction (n = 5). While no liver rejection was observed, plasma levels of immunosuppressive drugs increased in five. Twenty‐four patients developed progression (38% extrahepatic growth, 33% new extrahepatic lesions/vascular invasion). Median OS from regorafenib initiation was 12.9 (95% CI, 6.7‐19.1) and 38.4 months (95% CI, 18.5‐58.4) for the sorafenib initiation. This is the first study showing safety of regorafenib after LT, thus providing the rational of considering regorafenib in the clinical decision‐making in sorafenib‐tolerant patients with HCC recurrence after LT.
Medications for management of opioid use disorder.

PURPOSE The use of buprenorphine, methadone, and long-acting naltrexone for treatment of opioid use disorder (OUD) is discussed, including a review of current literature detailing treatment approaches and action steps to optimize treatment in acute care and office-based settings. SUMMARY The U.S. epidemic of opioid-related deaths has been driven by misuse of prescription opioids and, increasingly, illicit drugs such as heroin, fentanyl, and fentanyl analogs, necessitating a refocusing of treatment efforts on expanding access to life-saving, evidence-based OUD pharmacotherapy. Inpatient treatment of opioid withdrawal includes acute symptom control through a combination of nonopioid medications and long-term pharmacotherapy to lessen opioid craving and facilitate stabilization and recovery. Methadone and buprenorphine reduce opioid craving, increase treatment retention, reduce illicit opioid use, and increase overall survival. Buprenorphine has logistical advantages over methadone, such as greater flexibility of treatment setting and less risk of adverse effects. Studies have shown the efficacy of long-acting injectable naltrexone to be comparable to that of buprenorphine if patients are detoxified prior to initiation of therapy; however, patients with active OUD are often not able to complete the week-long period of opioid abstinence needed prior to initiation of naltrexone injections. Although buprenorphine is preferred by many patients and can be prescribed in office-based settings, there remains a paucity of physicians certified to prescribe it. CONCLUSION Buprenorphine has become the medication of choice for many patients with OUD, but its use is limited by the low number of physicians certified to prescribe the agent. Other agents studied for treatment of OUD include methadone and naltrexone.
Chemical Composition and Biological Activities of Metania and Drulia (Metaniidae) Freshwater Sponges from Amazonia

Sponges from freshwater environments, unlike marine's, are poorly known producers of natural compounds with medicinal purposes. Amazonian sponges produce massive large specimens and are widely spread, taxonomically diverse and their metabolites could represent a new frontier on unusual natural products to treat diseases such as Alzheimer's and Malaria. Species of Metania and Drulia (Metaniidae) genera are major contributors to the fauna of Amazonian freshwater sponges. Methanolic extracts from several species from these genera had their inhibitory activities evaluated in vitro, for parasite Plasmodium falciparum and acetyl and butyrylcholinesterase enzymes (AChE and BChE). All extracts were able to inhibit AChE, although no activity was observed towards BChE. Drulia uruguayensis extract was the most potent, inhibiting AChE with IC50=1.04 mg/mL. For antiplasmodial activity, all species showed inhibition to P. falciparum, but Metania reticulata being the most efficient with IC50=2.7 μg/mL. Mass spectrometry analyses evidenced the presence of fatty acids and sterols in active extracts.
Pharyngo-laryngeal involvement in systemic amyloidosis with cardiac involvement: a prospective observational study

Abstract Background: Systemic amyloidosis with cardiac involvement (CA) is a severe disease caused by the aggregation of misfolded proteins infiltrating organs and tissues and leading to their dysfunction. No study has yet focused on potential pharyngo-laryngeal impairments associated to CA. Our objective was to define its prevalence and describe pharyngo-laryngeal involvement patterns in a population with CA (light chain: AL, wild-type transthyretin: ATTRwt, variant transthyretin: ATTRv). Methods: Consecutive patients with a confirmed diagnosis of CA were prospectively investigated for pharyngo-laryngeal involvement. This included questionnaires on symptoms of dysphonia/dysphagia and quality of life Voice Handicap Index (VHI). In cases of dysphonia, a nasofibroscopy was performed to evaluate potential laryngeal organic lesions of amyloid infiltration and induced laryngeal dysfunction (mobility, glottic air leak). In cases of dysphagia, Video Endoscopy Swallowing Study (VESS) was performed to evaluate the presence of hypopharyngeal pooling at rest and during swallowing and the time of swallowing 80 ml of water. Results: Ninety-five CA patients were enrolled, of whom 19 were ATTRv, 36 AL and 40 ATTRwt. Their mean age was 73.8 ± 9.2 years and the sex ratio was 2.6 in favor of men. Dysphagia was reported in 17% of the patients and 40% had more specific oropharyngeal symptoms (food sticking, regurgitation, change in dietary habits), preceding the CA diagnosis by 7 (0–24) months. Recent weight loss was reported in 60% of the patients (mean loss of 10 ± 6.3 kg). VESS showed functional swallowing impairment in only 4 patients without any macroscopic organic lesion. Dysphonia was reported in 36% of the patients (44% and 47% in AL and ATTRv sub-groups, respectively) of whom 40% had functional or organic laryngeal abnormality (14% of vocal fold mobility dysfunction and 26% of abnormal mucosa) without any macroscopic-specific lesions of amyloid infiltration in these patients. Conclusions: This prospective study suggests, for the first time, that amyloid associated with CA could infiltrate the various anatomical structures of the pharyngo-larynx, responsible for functional impairment and potential nutritional depletion and poor quality of life.
An Omics Approach to Extracellular Vesicles from HIV-1 Infected Cells

Human Immunodeficiency Virus-1 (HIV-1) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS), infecting nearly 37 million people worldwide. Currently, there is no definitive cure, mainly due to HIV-1′s ability to enact latency. Our previous work has shown that exosomes, a small extracellular vesicle, from uninfected cells can activate HIV-1 in latent cells, leading to increased mostly short and some long HIV-1 RNA transcripts. This is consistent with the notion that none of the FDA-approved antiretroviral drugs used today in the clinic are transcription inhibitors. Furthermore, these HIV-1 transcripts can be packaged into exosomes and released from the infected cell. Here, we examined the differences in protein and nucleic acid content between exosomes from uninfected and HIV-1-infected cells. We found increased cyclin-dependent kinases, among other kinases, in exosomes from infected T-cells while other kinases were present in exosomes from infected monocytes. Additionally, we found a series of short antisense HIV-1 RNA from the 3′ LTR that appears heavily mutated in exosomes from HIV-1-infected cells along with the presence of cellular noncoding RNAs and cellular miRNAs. Both physical and functional validations were performed on some of the key findings. Collectively, our data indicate distinct differences in protein and RNA content between exosomes from uninfected and HIV-1-infected cells, which can lead to different functional outcomes in recipient cells.
Change in Mobility: Consistency of Estimates and Predictors across Studies of Older Adults.

OBJECTIVES This study compares estimates and determinants of within-individual changes in mobility across surveys of older US adults. METHOD Data come from the Health and Retirement Study (HRS) and the Midlife in the United States (MIDUS) study. Measures of mobility comprise self-reported level of difficulty with walking several blocks, going up several flights of stairs, lifting and carrying 10 pounds, and stooping. Predictors include sociodemographic characteristics and indicators of health and health behaviors. We pool the datasets and estimate weighted lagged dependent variable logistic regression models for each activity, assessing cross-study differences using interaction terms between a survey indicator and relevant variables. RESULTS Estimates of declines in mobility differ substantially across surveys for walking, lifting and carrying, and stooping, but there are no between-survey differences in the probability of (not) recovering from a limitation. With the exception of age, determinants of change are similar between studies. For lifting/carrying and stooping, the age-related increase in developing limitations is less steep at younger ages for HRS respondents than MIDUS respondents, but steeper at older ages. DISCUSSION To compare estimates of mobility change across surveys, mobility measures would need to be harmonized. Determinants of mobility change, however, are more comparable.
How Kaposi’s sarcoma-associated herpesvirus stably transforms peripheral B cells towards lymphomagenesis

Significance Primary effusion lymphoma (PEL) is a highly aggressive B cell lymphoma. PELs are associated with Kaposi’s sarcoma-associated herpesvirus (KSHV), and most of them are coinfected with Epstein–Barr virus (EBV). Human B cells have not previously been stably infected with KSHV in vitro. In this study, we have defined conditions to infect human B cells stably with KSHV and show that optimal infection requires coinfection by EBV. We show that a subset of these dually infected cells acquires multiple properties of PEL cells. This dual infection in vitro allows a mechanistic analysis of the contributions of EBV and KSHV to early steps in the development of PEL and underscores the desirability of targeting both viruses in developing new therapies for PEL. Primary effusion lymphomas (PELs) are causally associated with Kaposi’s sarcoma-associated herpesvirus (KSHV) and 86% of PELs are coinfected with Epstein–Barr virus (EBV). Understanding how PELs develop has been impaired by the difficulty of infecting B cells with KSHV in vitro, and the inability of KSHV to transform them. We show that EBV supports an optimal coinfection of 2.5% of peripheral B cells by KSHV. This coinfection requires 1 or more transforming genes of EBV but not entry into KSHV’s lytic cycle. We demonstrate that dually infected B cells are stably transformed in vitro and show that while both viruses can be maintained, different cells exhibit distinct, transformed properties. Transformed cells that grow to predominate in a culture express increased levels of most KSHV genes and differentially express a subset of cellular genes, as do bona fide PEL cells. These dually infected peripheral B cells are thus both stably transformed and allow in vitro molecular dissection of early steps in the progression to lymphomagenesis.
Phytoremediation of landfill leachate waste contaminants through floating bed technique using water hyacinth and water lettuce

Abstract In the present study, the effectiveness of water hyacinth and water lettuce was tested for the phytoremediation of landfill leachate for the period of 15 days. Fifteen plastic containers were used in experimental setup where aquatic plants were fitted as a floating bed with the help of thermo-pole sheet. It was observed that both plants significantly (p < 0.05/p < 0.01/p < 0.001) reduce the physicochemical parameters pH, TDS, BOD, COD and heavy metals like Zn, Pb, Fe, Cu and Ni from landfill leachate. Maximum reduction in these parameters was obtained at 50% and 75% landfill leachate treatment and their removal rate gradually increased from day 3 to day 15 of the experiment. The maximum removal rate for heavy metals such as for Zn (80–90%), Fe (83–87%) and Pb (76–84%) was attained by Eichhornia crassipes and Pistia stratiotes. Value of bioconcentration and translocation factor was less than 1 which indicates the low transport of heavy metals from roots to the above-ground parts of the plants. Both these plants accumulate heavy metals inside their body without showing much reduction in growth and showing tolerance to all the present metals. Therefore, results obtained from the study suggest that these aquatic plants are suitable candidate for the removal of pollution load from landfill leachate.
Does a computerized neuropsychological test predict prolonged recovery in concussed children presenting to the ED?

ABSTRACT Computerized neuropsychological tests (CNTs) are widely used internationally in concussion management. Their prognostic value for predicting recovery post-concussion is poorly understood, particularly in pediatric populations. The aim of the present study was to examine whether cognitive functioning (measured by CogSport) has prognostic value for predicting rapid versus slow recovery. This is a prospective longitudinal observational cohort study conducted at a state-wide tertiary pediatric hospital. Data were collected at 1–4, 14, and 90 days post-injury. Eligible children were aged ≥5 and <18 years presenting to the Emergency Department having sustained a concussion within 48 h. Concussion was defined according to the Zurich/Berlin Consensus Statement on Concussion in Sport. Dependent variables were reaction times and error rates on the CogSport Brief Battery. In total, 220 cases were analyzed; 98 in a rapid recovery group (asymptomatic at 14 days post-injury, mean age 11.5 [3.2], 73.5% male) and 122 in a slow recovery group (symptomatic at 14 days post-injury, mean age 12.0 [3.1], 69.7% male). Longitudinal GEE analyses modeled the trajectories of both mean log10-transformed reaction time and error rates between groups over time (1–4, 14 and 90 days). Both group main and interaction (time by group) terms for all models were non-significant (p > .05). Cognitive functioning, measured by CogSport and assessed within 1–4 days of concussion, does not predict prolonged recovery in a pediatric sample. Further, there were no significant group differences at any time point. Considering the widespread use and promotion of CNTs, it is important that clinicians understand the significant limitations of the CogSport battery.
Evidence of shared familial factors influencing neurocognitive endophenotypes in adult- and childhood-onset schizophrenia

Abstract Background The aggregation of neurocognitive deficits among the non-psychotic first-degree relatives of adult- and childhood-onset schizophrenia patients suggests that there may be a common etiology for these deficits in childhood- and adult-onset illness. However, there is considerable heterogeneity in the presentation of neurobiological abnormalities, and whether there are differences in the extent of familial transmission for specific domains of cognitive function has not been systematically addressed. Methods We employed variance components analysis, as implemented in SOLAR-Eclipse, to evaluate the evidence of familial transmission for empirically derived composite scores representing attention, working memory, verbal learning, verbal retention, and memory for faces. We contrast estimates for adult- and childhood-onset schizophrenia families and matched community control pedigrees, and compare our findings to previous reports based on analogous neurocognitive assessments. Results We observed varying degrees of familial transmission; attention and working memory yielded comparable, significant estimates for adult-onset and community control pedigrees; verbal learning was significant for childhood-onset and community control pedigrees; and facial memory demonstrated significant familial transmission only for childhood-onset schizophrenia. Model-fitting analyses indicated significant differences in familiality between adult- and childhood-onset schizophrenia for attention, working memory, and verbal learning. Conclusions By comprehensively assessing a wide range of neurocognitive domains in adult- and childhood-onset schizophrenia families, we provide additional support for specific neurocognitive domains as schizophrenia endophenotypes. Whereas comparable estimates of familial transmission for certain dimensions of cognitive functioning support a shared etiology of adult- and childhood-onset neurocognitive function, observed differences may be taken as preliminary evidence of partially divergent multifactorial architectures.
NEWS2 Is Superior to qSOFA in Detecting Sepsis with Organ Dysfunction in the Emergency Department

Early administration of antibiotics is associated with better survival in sepsis, thus screening and early detection for sepsis is of clinical importance. Current risk stratification scores used for bedside detection of sepsis, for example Quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score 2 (NEWS2), are primarily validated for death and intensive care. The primary aim of this study was to compare the diagnostic accuracy of qSOFA and NEWS2 for a composite outcome of sepsis with organ dysfunction, infection-related mortality within <72 h, or intensive care due to an infection. Retrospective analysis of data from two prospective, observational, multicentre, convenience trials of sepsis biomarkers at emergency departments were performed. Cohort A consisted of 526 patients with a diagnosed infection, 288 with the composite outcome. Cohort B consisted of 645 patients, of whom 269 had a diagnosed infection and 191 experienced the composite outcome. In Cohort A and B, NEWS2 had significantly higher area under receiver operating characteristic curve (AUC), 0.80 (95% CI 0.75–0.83) and 0.70 (95% CI 0.65–0.74), than qSOFA, AUC 0.70 (95% CI 0.66–0.75) and 0.62 (95% CI 0.57–0.67) p < 0.01 and, p = 0.02, respectively for the composite outcome. NEWS2 was superior to qSOFA for screening for sepsis with organ dysfunction, infection-related mortality or intensive care due to an infection both among infected patients and among undifferentiated patients at emergency departments.
Effects of Docosahexaenoic Acid on Chemokine Expression in Human Conjunctival Fibroblasts

ABSTRACT Purpose We assessed the production of chemokines by human conjunctival fibroblasts in response to inflammation and the effects of omega (ω)-3 fatty acids on chemokine expression. Methods Primary cultures of human conjunctival fibroblasts were incubated with interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α). The expression of eotaxin-1 and RANTES in response to pretreatment with docosahexaenoic acid (DHA) was investigated. Moreover, western blotting was used to evaluate the effects of DHA on the activation of nuclear factor (NF)-κB and signal transducer and activator of transcription 6 (STAT6). Results The expression of eotaxin-1 mRNA was significantly suppressed by pretreatment with DHA with IL-4 and TNF-α costimulation. RANTES expression was similarly suppressed, but the difference was not significant. The secretion of eotaxin-1 and RANTES was significantly lower in DHA-pretreated cells than in vehicle-treated cells. Western blotting for NF-κB and STAT6 showed that these proteins were downregulated in the DHA pretreatment group compared with those in the vehicle control group. Conclusion The results of this study suggested that DHA could have applications in the management of allergic inflammation.
Respiratory syncytial virus hospitalisations among young children: a data linkage study

Abstract We aimed to provide comprehensive estimates of laboratory-confirmed respiratory syncytial virus (RSV)-associated hospitalisations. Between 2012 and 2015, active surveillance of acute respiratory infection (ARI) hospitalisations during winter seasons was used to estimate the seasonal incidence of laboratory-confirmed RSV hospitalisations in children aged <5 years in Auckland, New Zealand (NZ). Incidence rates were estimated by fine age group, ethnicity and socio-economic status (SES) strata. Additionally, RSV disease estimates determined through active surveillance were compared to rates estimated from hospital discharge codes. There were 5309 ARI hospitalisations among children during the study period, of which 3923 (73.9%) were tested for RSV and 1597 (40.7%) were RSV-positive. The seasonal incidence of RSV-associated ARI hospitalisations, once corrected for non-testing, was 6.1 (95% confidence intervals 5.8–6.4) per 1000 children <5 years old. The highest incidence was among children aged <3 months. Being of indigenous Māori or Pacific ethnicity or living in a neighbourhood with low SES independently increased the risk of an RSV-associated hospitalisation. RSV hospital discharge codes had a sensitivity of 71% for identifying laboratory-confirmed RSV cases. RSV infection is a leading cause of hospitalisation among children in NZ, with significant disparities by ethnicity and SES. Our findings highlight the need for effective RSV vaccines and therapies.