Miracle-dz/UniFAR-FTUs huggingface dataset:
Nephrogenic Systemic Fibrosis Risk Assessment and Skin Biopsy Quantification in Patients with Renal Disease following Gadobenate Contrast Administration

BACKGROUND AND PURPOSE: Nephrogenic systemic fibrosis following administration of intravenous gadobenate during MR imaging is rare. This study aimed to analyze any nephrogenic systemic fibrosis–related risks and quantify skin gadolinium levels in patients with impaired renal function but without nephrogenic systemic fibrosis who had received gadobenate. MATERIALS AND METHODS: In this retrospective study with a prospective skin biopsy phase, patients with estimated glomerular filtration rates of <60 mL/min/1.73 m2 undergoing contrast-enhanced MR imaging from July 2007 through June 2014 were screened for nephrogenic systemic fibrosis using a questionnaire. This was highly sensitive but not specific and reliably excluded nephrogenic systemic fibrosis if responses to at least 6 of the 8 questions were negative. If no nephrogenic systemic fibrosis was detected, a skin biopsy was requested. RESULTS: Of 2914 patients who met these criteria, 1988 were excluded for various reasons. Of the remaining 926 patients, 860 were screened negative for nephrogenic systemic fibrosis. Of these, 17 (2%) had estimated glomerular filtration rates of <15 mL/min/1.73 m2, 51 (6%) had levels of 15 < 30 mL/min/1.73 m2, 234 (27%) had levels of 30 < 45 mL/min/1.73 m2, and 534 (62%) had levels of 45 < 60 mL/min/1.73 m2. Of the 66 who were not cleared of nephrogenic systemic fibrosis by the questionnaire, 6 patients were evaluated by a dermatologist and confirmed not to have nephrogenic systemic fibrosis (no biopsy required). CONCLUSIONS: A diagnosis of nephrogenic systemic fibrosis was excluded in 860 patients with impaired renal function who were followed up and received gadobenate during MR imaging. In 14 such patients who underwent at least 1 gadobenate-enhanced MR imaging examination and did not have nephrogenic systemic fibrosis, gadolinium levels in the skin were exceedingly low.
ASPEN Consensus Recommendations for Refeeding Syndrome.

INTRODUCTION In the spring of 2017, the American Society for Parenteral and Enteral Nutrition (ASPEN) Parenteral Nutrition Safety Committee and the Clinical Practice Committee convened an interprofessional task force to develop consensus recommendations for identifying patients with or at risk for refeeding syndrome (RS) and for avoiding and managing the condition. This report provides narrative review and consensus recommendations in hospitalized adult and pediatric populations. METHODS Because of the variation in definitions and methods reported in the literature, a consensus process was developed. Subgroups of authors investigated specific issues through literature review. Summaries were presented to the entire group for discussion via email and teleconferences. Each section was then compiled into a master document, several revisions of which were reviewed by the committee. FINDINGS/RECOMMENDATIONS This group proposes a new clinical definition, and criteria for stratifying risk with treatment and screening strategies. The authors propose that RS diagnostic criteria be stratified as follows: a decrease in any 1, 2, or 3 of serum phosphorus, potassium, and/or magnesium levels by 10%-20% (mild), 20%-30% (moderate), or >30% and/or organ dysfunction resulting from a decrease in any of these and/or due to thiamin deficiency (severe), occurring within 5 days of reintroduction of calories. CONCLUSIONS These consensus recommendations are intended to provide guidance regarding recognizing risk and identifying, stratifying, avoiding and managing RS. This consensus definition is additionally intended to be used as a basis for further research into the incidence, consequences, pathophysiology, avoidance, and treatment of RS.
Excess length of hospital stay, mortality and cost attributable to Clostridioides (Clostridium) difficile infection and recurrence: a nationwide analysis in Japan

Abstract Clostridioides (Clostridium) difficile infection (CDI) is the leading cause of infectious diarrhoea in hospitalised patients, representing a substantial economic burden driven mainly by increased length of hospital stay (LoS). Currently in Japan, limited evidence on CDI-associated excess LoS is available. We conducted a retrospective, matched-cohort study using a large, Japanese, hospital-based administrative database. CDI was defined as CDI treatment plus either CDI diagnosis or positive enzyme immunoassay result. Propensity score matching at the time of CDI or recurrent CDI (rCDI) onset was applied to adjust baseline confounding and immortal time bias. The analysis included 5 994 054 hospitalisation records during 2008–2017, of which 11 823 were identified as CDI and 1359 as rCDI. The median excess LoS attributable to CDI and rCDI was 3 days and 6.5 days, respectively. The excess mortality attributable to CDI was 6.9%; there was no excess mortality attributable to rCDI (−1.9%). The median difference in costs attributable to CDI and rCDI during the residual stay was JPY 130 296 (USD 1185) and JPY 81 054 (USD 737) per hospitalisation, respectively. By adjusting the biases, the burden of CDI in Japan was evaluated. The findings could support decision making and resource allocation for CDI management in Japanese hospitals.
Incidence of hepatitis B virus infection among human immunodeficiency virus-infected treatment naïve adults in Botswana

Abstract Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection is highest in sub-Saharan Africa and results in accelerated clinical outcomes compared with HBV or HIV mono-infection. HBV clearance rates are higher in healthy adults; however, in sub-Saharan Africa, there are limited data on clearance of incident HBV in HIV-infected adults. Therefore, we sought to estimate HBV incidence and HBV surface antigen (HBsAg) clearance in HIV-infected adults in Botswana. This was a retrospective longitudinal study of 442 HIV-1C infected treatment naïve patients enrolled in a previous Botswana Harvard AIDS Institute Partnership study. Archived plasma samples from 435 HIV-infected treatment naïve participants were screened for HBsAg and HBV core antibody (anti-HBc). HBsAg was evaluated annually over a 4-year period, and HBV deoxyribonucleic acid (DNA) levels of HBsAg-positive chronic and incident patients were quantified. Baseline median CD4+ T-cell count was 458 cells/μL [Q1, Q3: 373, 593], and median HIV viral load was 4.15 copies/mL [Q1, Q3: 3.46, 4.64]. Twenty two HBV incident cases occurred, representing an incidence of 3.6/100 person-years [95% CI: 2.2–5.6]. All incident HBV cases with a follow-up sample available for screening (13/22) cleared HBsAg. Detectable HBV viral loads among chronic and incident cases ranged between 5.15 × 101 to 1.4 × 107 IU/L and 1.80 × 101 to 1.7 × 108 IU/mL, respectively. We report high HBV incidence associated with elevated HBV DNA levels despite high CD4+ T-cell counts in HIV-infected patients in Botswana. These incidence cases represent a potential source of HBV transmission in the population. Scaling-up of HIV treatment strategies utilizing antiretroviral therapy regimens with anti-HBV activity coupled with screening for HBV infections in households of the HBsAg-positive cases is recommended.
Two near-inertial peaks in antiphase controlled by stratification and tides in the Yellow Sea

The Yellow Sea is a strongly tidally-driven and highly stratified shallow sea due to the presence of the Yellow Sea Cold Water Masses. Observations show that the near-inertial event sustains for 10 days with a peak near-inertial velocity of 0.15m/s, which accounts for 30% of the total velocity during the passage of a cyclone. Near-inertial velocity is dominated by the first baroclinic mode with one zero-crossing at the depth of the maximum stratification and two velocity peaks in the mixed layer and below the thermocline, respectively. Combined with numerical simulation analysis, it was found that the two velocity peaks are controlled by stratification and tides. In the mixed layer, the near-inertial peak is induced by wind stress, but the strong stratification constrains the downward propagation of the near-inertial energy. With respect to the near-inertial peak below the thermocline, it is associated with a barotropic wave generated at the coast and propagating offshore. However, the near-inertial flow within the bottom layer is reduced by the eddy viscosity of the tidal currents. Within the thermocline, the pronounced vertical convection due to velocity shear weakens the intensity of the near-inertial flow.
Immediate effects of noxious and innocuous thermal stimulation on brain activation in patients with stroke

Abstract Case-control studies have shown that noxious thermal stimulation (TS) can improve arm function in patients with stroke. However, the neural mechanisms underlying this improvement are largely unknown. We explored functional neural activation due to noxious and innocuous TS intervention applied to the paretic arm of patients with stroke. Sixteen participants with unilateral cortical infarctions were allocated to one of two groups: noxious TS (8 patients; temperature combination: hot pain 46°C to 47°C, cold pain 7°C–8°C) or innocuous TS (n = 8; temperature combination: hot 40°C–41°C, cold 20°C–21°C). All subjects underwent fMRI scanning before and after 30 min TS intervention and performed a finger tapping task with the affected hand. Immediate brain activation effects were assessed according to thermal type (noxious vs. innocuous TS) and time (pre-TS vs post-TS). Regions activated by noxious TS relative to innocuous TS (P < .05, adjusted for multiple comparisons) were related to motor performance and sensory function in the bilateral primary somatosensory cortices, anterior cingulate cortex, insula, thalamus, hippocampus and unilateral primary motor cortex, secondary somatosensory cortex at the contralateral side of lesion, and unilateral supplementary motor area at the ipsilateral side of lesion. Greater activation responses were observed in the side contralateral to the lesion, suggesting a significant intervention effect. Our preliminary findings suggest that noxious TS may induce neuroplastic changes unconstrained to the local area. Trial registration: NCT01418404
Public Stigma Toward Persons with Suicidal Thoughts-Do Age, Sex, and Medical Condition of Affected Persons Matter?

OBJECTIVE Suicidal persons often face public stigmatization which affects help-seeking behavior and may lead to an additional suicide risk. There is not much known about differences in stigmatizing attitudes concerning characteristics of affected persons. The present study investigates public stigma toward suicidal persons in Germany by focussing on differences concerning sex, age, and medical condition of the affected person. METHOD A national telephone survey (N = 2,002) was conducted using case vignettes presenting a person with suicidal thoughts. Vignettes systematically varied in sex, age, and medical condition (depressive symptoms vs. cancer). Several components of stigma were assessed ("weakness of will" as a cause, separation, negative emotional reactions, and desire for social distance). RESULTS About 44% of the respondents agreed that a cause of suicidal thoughts is "weakness of will," and two thirds disagreed that they would feel and think the same as the described person. In terms of emotional reactions, fear was more pronounced than anger. Stigmatizing attitudes were particularly pronounced when the described person was female and depressive symptoms were presented. CONCLUSIONS Magnitude of public suicide stigma varies depending on the characteristics of the described person. Groups that are at special risk of being stigmatized should be considered in antistigma programs.
Monazite transformation into Ce- and La-containing oxalates by Aspergillus niger.

Monazite is a naturally-occurring lanthanide (Ln) phosphate mineral [Lnx (PO4 )y ] and is the main industrial source of the rare earth elements (REE), cerium and lanthanum. Endeavours to ensure the security of supply of elements critical to modern technologies view bioprocessing as a promising alternative or adjunct to new methods of element recovery. However, relatively little is known about microbial interactions with REE. Fungi are important geoactive agents in the terrestrial environment and well known for properties of mineral transformations, particularly phosphate solubilization. Accordingly, this research examined the capability of a ubiquitous geoactive soil fungus, Aspergillus niger, to affect the mobility of REE in monazite and identify possible mechanisms for biorecovery. It was found that A. niger could grow in the presence of monazite and mediated the formation of secondary Ce and La-containing biominerals with distinct morphologies including thin sheets, orthorhombic tablets, acicular needles, and rosette aggregates which were identified as cerium oxalate decahydrate (Ce2 (C2 O4 )3 ·10H2 O) and lanthanum oxalate decahydrate (La2 (C2 O4 )3 ·10H2 O). In order to identify a means for biorecovery of REE via oxalate precipitation the bioleaching and bioprecipitation potential of biomass-free spent culture supernatants was investigated. Although such indirect bioleaching of REE was low from the monazite with maximal lanthanide release reaching >40 mg L-1 , leached REE were efficiently precipitated as Ce and La oxalates of high purity, and did not contain Nd, Pr and Ba, present in the original monazite. Geochemical modelling of the speciation of oxalates and phosphates in the reaction system confirmed that pure Ln oxalates can be formed under a wide range of chemical conditions. These findings provide fundamental knowledge about the interactions with and biotransformation of REE present in a natural mineral resource, and indicate the potential of oxalate bioprecipitation as a means for efficient biorecovery of REE from solution. This article is protected by copyright. All rights reserved.
A plant‐specific SWR1 chromatin‐remodeling complex couples histone H2A.Z deposition with nucleosome sliding

Deposition of H2A.Z in chromatin is known to be mediated by a conserved SWR1 chromatin‐remodeling complex in eukaryotes. However, little is known about whether and how the SWR1 complex cooperates with other chromatin regulators. Using immunoprecipitation followed by mass spectrometry, we found all known components of the Arabidopsis thaliana SWR1 complex and additionally identified the following three classes of previously uncharacterized plant‐specific SWR1 components: MBD9, a methyl‐CpG‐binding domain‐containing protein; CHR11 and CHR17 (CHR11/17), ISWI chromatin remodelers responsible for nucleosome sliding; and TRA1a and TRA1b, accessory subunits of the conserved NuA4 histone acetyltransferase complex. MBD9 directly interacts with CHR11/17 and the SWR1 catalytic subunit PIE1, and is responsible for the association of CHR11/17 with the SWR1 complex. MBD9, TRA1a, and TRA1b function as canonical components of the SWR1 complex to mediate H2A.Z deposition. CHR11/17 are not only responsible for nucleosome sliding but also involved in H2A.Z deposition. These results indicate that the association of the SWR1 complex with CHR11/17 may facilitate the coupling of H2A.Z deposition with nucleosome sliding, thereby co‐regulating gene expression, development, and flowering time.
Evaluation of zonisamide for the treatment of focal epilepsy: a review of pharmacokinetics, clinical efficacy and adverse effects

ABSTRACT Introduction: Zonisamide is a benzisoxazole with 3-methanesulfonamide side chain, chemically unrelated with other anticonvulsants, and approved as mono-therapy of newly diagnosed focal epilepsy with or without secondary generalization in adults or adjunctive therapy in the treatment of partial seizures, with or without secondary generalization, in adults, adolescents, and children aged 6 years and above. Areas covered: Pharmacokinetics, clinical efficacy, and the adverse effects of zonisamide are discussed in the article. The discussion is based on data from published preclinical studies, clinical trials, observational studies, systematic reviews, and approved summary of product characteristics. Expert opinion: Zonisamide is an anticonvulsant with multiple mechanisms of action on neuronal tissue, which achieves seizure freedom in more than 80% of patients with newly-onset focal epilepsy and in 6.2 to 18.1% of patients with focal onset seizures inadequately controlled by first-line anticonvulsants. Within the recommended dose range, it follows linear kinetic of elimination; it is metabolized in the liver by two cytochrome isoforms, so pharmacokinetic interactions are rare and with little clinical significance. Up to 10% of patients taking zonisamide will have problems with weight loss and more than 10% with irritability, confusion or depression, and long-lasting therapy may cause renal calculi in 1.2% of patients.
Psychological and Pain Sensitization Characteristics Are Associated With Patellofemoral Osteoarthritis Symptoms: The Multicenter Osteoarthritis Study

Objective Determine the relation of symptomatic and structural features of patellofemoral osteoarthritis (PFOA) to psychological characteristics and measures of pain sensitization, in older adults with or at risk of knee osteoarthritis (OA). Methods This study included 1112 participants from the Multicenter Osteoarthritis Study (713 females, mean age 66.8 ± SD 7.6 yrs, body mass index 29.5 ± 4.8 kg/m2). Participants were grouped based on the presence of PFOA symptoms (anterior knee pain and pain on stairs) and magnetic resonance imaging (MRI) PFOA (full-thickness cartilage lesion with bone marrow lesion): (1) patellofemoral (PF) symptoms with MRI PFOA; (2) PF symptoms without MRI PFOA; (3) MRI PFOA without PF symptoms; and (4) no PF symptoms or MRI PFOA (no PFOA). Relation of PFOA classification to depressive symptoms, catastrophizing, temporal summation (TS) and pressure pain thresholds (PPT) was evaluated using logistic (categorical variables) and linear regression (continuous variables). Results Compared with no PFOA, those with PF symptoms with or without MRI PFOA had significantly greater odds of depressive symptoms, catastrophizing, and patellar TS (OR range 1.5–2.01), and those with PF symptoms without MRI PFOA had significantly greater odds of wrist TS (OR 1.66). Males with PF symptoms without MRI PFOA had significantly lower pressure PPT at the patella compared with no PFOA and those with MRI PFOA only (no symptoms). There were no significant differences at the wrist for males, or the patella or wrist for females. Conclusion Persons with PFOA symptoms, regardless of MRI PFOA status, are more likely to demonstrate depressive symptoms, catastrophizing, and TS. Males with PFOA symptoms without MRI PFOA demonstrate local hyperalgesia.
TRAPPing a neurological disorder: from yeast to humans

ABSTRACT The modular complex TRAPP acts as an activator of a subgroup of Ypt/RAB GTPases. The substrate GTPases and TRAPP are conserved from yeast to human cells, required for secretion and macroautophagy/autophagy and implicated in human disease. All TRAPP complexes contain four core subunits essential for cell viability, and until recently there were no human diseases associated with any core TRAPP subunit. Recently, we reported a neurological disorder associated with a pathogenic variant of the core TRAPP subunit TRAPPC4. This variant results in lower levels of full-length TRAPPC4 protein and the TRAPP complex. A conditional mutation of the yeast homolog of TRAPPC4, Trs23, also results in a lower level of the protein and the TRAPP complex. Phenotypic analysis of the yeast mutant cells reveals a minor defect in secretion and a major defect in autophagy. Similarly, primary fibroblasts derived from human patients also exhibit minor and severe defects in secretion and autophagy, respectively. We propose that the autophagy defect caused by the pathogenic-TRAPPC4 variant results in the severe neurological disorder. Moreover, we hypothesize that low levels of the core TRAPP complex are more detrimental to autophagy than to secretion, and that the long-term autophagy defect is especially harmful to neuronal cells. Abbreviations: ER: endoplasmic reticulum; PM: plasma membrane; TRAPP: transport protein particle; Ypt: yeast protein transport
Serum MicroRNA Signature as a Diagnostic and Therapeutic Marker in Patients with Psoriatic Arthritis

Objective MicroRNA (miRNA) are small endogenous regulatory RNA molecules that have emerged as potential therapeutic targets and biomarkers in autoimmunity. Here, we investigated serum miRNA levels in patients with psoriatic arthritis (PsA) and further assessed a serum miRNA signature in therapeutic responder versus nonresponder PsA patients. Methods Serum samples were collected from healthy controls (HC; n = 20) and PsA patients (n = 31), and clinical demographics were obtained. To examine circulatory miRNA in serum from HC and PsA patients, a focused immunology miRNA panel was analyzed utilizing a miRNA Fireplex assay (FirePlex Bioworks Inc.). MiRNA expression was further assessed in responders versus nonresponders according to the European League Against Rheumatism response criteria. Results Six miRNA (miR-221-3p, miR-130a-3p, miR-146a-5p, miR-151-5p, miR-26a-5p, and miR-21-5p) were significantly higher in PsA compared to HC (all P < 0.05), with high specificity and sensitivity determined by receiver-operating characteristic curve analysis. Analysis of responder versus nonresponders demonstrated higher baseline levels of miR-221-3p, miR-130a-3p, miR-146a-5p, miR-151-5p, and miR-26a-5p were associated with therapeutic response. Conclusion This study identified a 6-serum microRNA signature that could be attractive candidates as noninvasive markers for PsA and may help to elucidate the disease pathogenesis.
A protein quality control pathway at the mitochondrial outer membrane

Maintaining the essential functions of mitochondria requires mechanisms to recognize and remove misfolded proteins. However, quality control (QC) pathways for misfolded mitochondrial proteins remain poorly defined. Here, we establish temperature-sensitive (ts-) peripheral mitochondrial outer membrane (MOM) proteins as novel model QC substrates in Saccharomyces cerevisiae. The ts- proteins sen2-1HAts and sam35-2HAts are degraded from the MOM by the ubiquitin-proteasome system. Ubiquitination of sen2-1HAts is mediated by the ubiquitin ligase (E3) Ubr1, while sam35-2HAts is ubiquitinated primarily by San1. Mitochondria-associated degradation (MAD) of both substrates requires the SSA family of Hsp70s and the Hsp40 Sis1, providing the first evidence for chaperone involvement in MAD. In addition to a role for the Cdc48-Npl4-Ufd1 AAA-ATPase complex, Doa1 and a mitochondrial pool of the transmembrane Cdc48 adaptor, Ubx2, are implicated in their degradation. This study reveals a unique QC pathway comprised of a combination of cytosolic and mitochondrial factors that distinguish it from other cellular QC pathways.