Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the criteria of hepatorenal syndrome type of acute kidney injury in patients with cirrhosis admitted to ICU

Abstract Introduction: Acute kidney injury (AKI) is a common and devastating complication in patients with cirrhosis. In 2015, the International Club of Ascites (ICA) proposed the definition of hepatorenal syndrome (HRS) type of AKI (HRS-AKI) in patients with cirrhosis. This study aims to evaluate the criteria of HRS-AKI in patients with cirrhosis admitted to ICU with regard to the prognosis. Methods: A total of 349 cirrhotic patients consecutively admitted to intensive care unit (ICU) from 2010 to 2017 were retrospectively analyzed. Demographic parameters and clinical variables were collected with case report forms. The occurrence of AKI was determined according to ICA-AKI criteria. The phenotypes of AKI comprised pre-renal azotemia (PRA), acute tubular necrosis (ATN) and HRS. In our study, patients with PRA or ATN were classified to the non-HRS-AKI group. Results: The incidence of AKI was 73.0%, comprising PRA (18.6%), ATN (16.3%) and HRS (38.1%). The overall hospital mortality was 64.5%. Patients with AKI had a significantly higher in-hospital (76.1%) and 180-d (86.7%) mortality. AKI type was an independent risk factor for in-hospital mortality by a multivariate logistic regression. The in-hospital and 180-d mortality rates were of no significant difference among patients with HRS-AKI stages 1–3. Conclusions: AKI is common in patients with cirrhosis admitted to ICU, associated with significant in-hospital mortality. HRS-AKI was the most common and severe type of AKI in patients with cirrhosis admitted to ICU. The current staging system may not be applicable for HRS-AKI in patients with cirrhosis admitted to ICU.
Social Functioning and Suicide Risk in a Community Sample of Adolescents

Suicide is the second leading cause of death among young people. Both mental illness and social factors are associated with suicide in adolescents, and youth with mental disorders often experience social deficits, which may compound risk. The cumulative effects of mental disorders and social factors on suicidal ideation and behaviors (SIB) in adolescents have not previously been explored. Adolescents 13–18 years of age (N = 6,447; 49% female, 65% non-Hispanic White) participated in the National Comorbidity Survey Replication Adolescent Supplement. Adolescents were interviewed to assess mental health diagnoses, history of SIB, and relationship quality. Parents completed self-reports about adolescent mental health and family characteristics. Logistic regression estimated associations of friend, sibling, and family relationships with 12-month SIB and lifetime suicide attempt (SA); associations between relationships, SIB, and SA were compared across classes of mental disorders. Friendship negativity (odds ratio [OR] = 1.20, 95% confidence interval (CI) [1.04, 1.40]), and family conflict (OR = 1.26, 95% CI [1.13, 1.41]), were positively associated with SIB, beyond the risk conferred by mental disorders, particularly mood disorders (OR = 4.75, 95% CI [3.20, 7.05]). Friendship positivity (OR = 0.89, 95% CI [0.80, 0.99]); sibling relationship positivity (OR = 0.79, 95% CI [0.68, 0.91]); family cohesion (OR = 0.77, 95% CI [0.69, 0.87]); maternal care (OR = 0.76, 95% CI [0.69, 0.84]); and paternal care (OR = 0.68, 95% CI [0.59, 0.78]), were inversely associated with SIB. Sibling relationship positivity, family conflict, and paternal care were similarly associated with SA. Self-reported adolescent friend and family relationship characteristics are associated with SIB and SA beyond the risk conferred by mental disorders. This suggests that perceptions of friend and family relationships may be an appropriate target to reduce suicide risk among adolescents.
The assesment of relationship between the angulation of impacted mandibular third molar teeth and the thickness of lingual bone: A prospective clinical study

Background Our purpose was to investigate the relationship between the angulation of mandibular third molars and the thickness of the lingual bone, which can affect the risk of lingual nerve damage during lower third molars surgical extraction. Material and Methods This study consisted of 104 patients (42 males and 62 females), aged between 18-42 years (24.67 ± 6.11 years). Cone Beam Computed Tomography (CBCT) images were taken for preoperative assessment. The teeth were divided into four groups according to their positions: mesioangular, distoangular, vertical and horizontal. Lingual bone thickness around impacted teeth were measured at three points: cementoenamel junction (CEJ) of the mandibular second molar, mid-root of the impacted third molar, and apex of the impacted third molar root. Two predisposing factors of lingual nerve damage were recorded: lingual bone perforated by the impacted tooth and lingual bone thinner than 1 mm. Additionally, buccolingual angulations of the teeth in each group were measured. Impacted mandibular third molars were removed in usual way. One week after surgery, the patients were evaluated regarding lingual nerve paresthesia. Results None of the 104 patients experienced paresthesia, including the ones who had teeth with close proximity with lingual nerve. The mean thickness of bone was 1.21±0.63 mm at CEJ of the second molar; 1.25±1.02 mm at the mid-root; and 1.06±1.31 mm at the apex. Horizontally impacted teeth had thinner lingual bone at mid-root level (p=0.016). Buccolingual angulated teeth were more often associated with perforated lingual bone (p=0.002). Buccolingual and mesial/distal angulation had negative correlation with lingual bone thickness (p<0.05). Conclusions As the buccolingual and mesiodistal angulations increase, lingual bone thickness decreases. Horizontally impacted teeth seemed to compromise the integrity of the lingual bone more than impacted teeth in other positions. During the surgery, thin or perforated lingual bone may result in displacement of the impacted tooth lingually. Key words:Lingual bone, impacted third molar, cone beam computed tomography, angulation, paresthesia.
A review of the atomoRapid HIV self-testing device: an acceptable and easy alternative to facilitate HIV testing

ABSTRACT Introduction:HIV testing is the gateway to both HIV prevention and treatment, and increased HIV testing and linkage to services is vital for an effective HIV response. HIV testing has progressed significantly from a lengthy laboratory process conducted by specialist medical staff to rapid point of care testing performed by trained lay staff. Despite HIV testing services being widely available, testing rates remain suboptimal among young people and men. Alternative delivery strategies that complement conventional testing services are needed to reach these priority groups. Areas covered:This article reviewed the AtomoRapid HIV self-testing (HIVST) device as an innovative alternative to conventional testing. Expert commentary:HIVST complements traditional HIV testing options and can be used to overcome major barriers to testing by catering for testing outside of conventional settings and by allowing individuals to test themselves privately, and at their own discretion and frequency. We conclude that the high sensitivity, specificity, acceptability, usability, and fidelity of this device makes it an appropriate option for the enhancement of HIV testing strategies for harder to reach populations, such as young people and men.
Functional Comparison of XPF Missense Mutations Associated to Multiple DNA Repair Disorders

XPF endonuclease is one of the most important DNA repair proteins. Encoded by XPF/ERCC4, XPF provides the enzymatic activity of XPF-ERCC1 heterodimer, an endonuclease that incises at the 5’ side of various DNA lesions. XPF is essential for nucleotide excision repair (NER) and interstrand crosslink repair (ICLR). XPF/ERCC4 mutations are associated with several human diseases: Xeroderma Pigmentosum (XP), Segmental Progeria (XFE), Fanconi Anemia (FA), Cockayne Syndrome (CS), and XP/CS combined disease (XPCSCD). Most affected individuals are compound heterozygotes for XPF/ERCC4 mutations complicating the identification of genotype/phenotype correlations. We report a detailed overview of NER and ICLR functional studies in human XPF-KO (knock-out) isogenic cells expressing six disease-specific pathogenic XPF amino acid substitution mutations. Ultraviolet (UV) sensitivity and unscheduled DNA synthesis (UDS) assays provide the most reliable information to discern mutations associated with ICLR impairment from mutations related to NER deficiency, whereas recovery of RNA synthesis (RRS) assays results hint to a possible role of XPF in resolving R-loops. Our functional studies demonstrate that a defined cellular phenotype cannot be easily correlated to each XPF mutation. Substituted positions along XPF sequences are not predictive of cellular phenotype nor reflect a particular disease. Therefore, in addition to mutation type, allelic interactions, protein stability and intracellular distribution of mutant proteins may also contribute to alter DNA repair pathways balance leading to clinically distinct disorders.
The impact of different rheumatic diseases on health-related quality of life: a comparison with a selected sample of healthy individuals using SF-36 questionnaire, EQ-5D and SF-6D utility values

Background: Given the high prevalence of rheumatic diseases, there is a need to determine which conditions have the greatest impact on health-related quality of life (HRQoL). The main aim of this study was to explore the HRQoL scores among 14 different rheumatic diseases and to compare them with the results of a selecting sample of healthy controls. Methods: 2633 patients of an ongoing cohort have been enrolled. Rheumatic diseases were classified into five diagnostic groups: inflammatory rheumatic diseases, connective tissue disorders, symptomatic peripheral osteoarthritis, soft tissue disorders, and osteoporosis. For comparison were used 649 healthy controls. The HRQoL was evaluated with the Medical Outcomes Study Short-Form 36 Health Survey (SF-36), the EuroQol five Dimensions (EQ-5D) questionnaire, and the Short-Form six Dimensions (SF-6D) questionnaire. Results: The five major rheumatic disease groups, compared to healthy people, significantly impaired all eight health concepts of the SF-36 (p <0.0001). Similar results were found for EQ-5D and SF-6D. The patients with inflammatory rheumatic diseases have poorer self-reported health status than those without arthritis in all domains of living, but particularly with respect to scales measuring aspects of physical functioning or mobility, role limitation due to physical health problems and usual activities, and bodily pain. Rheumatoid arthritis had the largest negative impact on HRQoL, followed by fibromyalgia, vertebral fractures due to osteoporosis, hip osteoarthritis, and systemic sclerosis. Conclusions: Our results indicate that rheumatic diseases have a clearly detrimental effect on the HRQoL, and physical domain is more impaired than mental and social ones. (www.actabiomedica.it)
Association of Magnetic Resonance Imaging and a 12-Gene Expression Assay With Breast Ductal Carcinoma In Situ Treatment.

Importance Advanced diagnostics, such as magnetic resonance imaging (MRI) and gene expression profiles, are potentially useful to guide targeted treatment in patients with ductal carcinoma in situ (DCIS). Objectives To examine the proportion of patients who converted to mastectomy after MRI and the reasons for those conversions and to measure patient adherence to radiotherapy guided by the 12-gene DCIS score. Design, Setting, and Participants Analysis of a prospective, cohort, nonrandomized clinical trial that enrolled women with DCIS on core biopsy who were candidates for wide local excision (WLE) from 75 institutions from March 25, 2015, to April 27, 2016, through the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network trial E4112. Interventions Participants underwent breast MRI before surgery, and subsequent management incorporated MRI findings for choice of surgery. The DCIS score was used to guide radiotherapy recommendations among women with DCIS who had WLE as the final procedure and had tumor-free excision margins of 2 mm or greater. Main Outcomes and Measures The primary end point was to estimate the conversion rate to mastectomy and the reason for conversion. Results Of 339 evaluable women (mean [SD] age, 59.1 [10.1] years; 262 [77.3%] of European descent) eligible for WLE before MRI, 65 (19.2%; 95% CI, 15.3%-23.7%) converted to mastectomy. Of these 65 patients, conversion was based on MRI findings in 25 (38.5%), patient preference in 25 (38.5%), positive margins after attempted WLE in 10 (15.4%), positive genetic test results in 3 (4.6%), and contraindication to radiotherapy in 2 (3.1%). Among the 285 who had WLE performed after MRI as the first surgical procedure, 274 (96.1%) achieved successful breast conservation. Of 171 women eligible for radiotherapy guided by DCIS score (clear margins, absence of invasive disease, and score obtained), the score was low (<39) in 82 (48.0%; 95% CI, 40.6%-55.4%) and intermediate-high (≥39) in 89 (52.0%; 95% CI, 44.6%-59.4%). Of these 171 patients, 159 (93.0%) were adherent with recommendations. Conclusions and Relevance Among women with DCIS who were WLE candidates based on conventional imaging, multiple factors were associated with conversion to mastectomy. This study may provide useful preliminary information required for designing a planned randomized clinical trial to determine the effect of MRI and DCIS score on surgical management, radiotherapy, overall resource use, and clinical outcomes, with the ultimate goal of achieving greater therapeutic precision. Trial Registration ClinicalTrials.gov identifier: NCT02352883.
RNA Editors, Cofactors, and mRNA Targets: An Overview of the C-to-U RNA Editing Machinery and Its Implication in Human Disease

One of the most prevalent epitranscriptomic modifications is RNA editing. In higher eukaryotes, RNA editing is catalyzed by one of two classes of deaminases: ADAR family enzymes that catalyze A-to-I (read as G) editing, and AID/APOBEC family enzymes that catalyze C-to-U. ADAR-catalyzed deamination has been studied extensively. Here we focus on AID/APOBEC-catalyzed editing, and review the emergent knowledge regarding C-to-U editing consequences in the context of human disease.
Can expressed prostatic secretions affect prostate biopsy decision of urologist?

ABSTRACT Objectives: To evaluate the frequency of NIH category IV prostatitis, and the use of expressed prostatic secretions tests in an effort to improve the reliability of prostate specific antigen as an indicator, to avoid unnecessary prostate biopsy. Materials and Methods: 178 expressed prostatic secretion positive patients with serum prostate specific antigen levels of ≥ 2.5 ng / mL were included in present prospective study. The diagnostic evaluation included detailed history and physical examination, digital rectal examination, urine analysis, urine culture, and expressed prostatic secretions tests. Transrectal ultrasonography was used both to measure prostate volume and conduct 12 core prostate biopsy. Results: The prevalence of NIH category IV prostatitis was 36.9% (178 / 482) in our population of men. In our study patients (n: 178) prostate biopsy results were classified as; 66 prostatitis, 81 BPH, and 31 Pca. In asymptomatic prostatitis group, expressed prostatic secretion mean leucocyte ratio was higher compared to other two groups (p < 0.0001). The relation between number of expressed prostatic secretion leucocytes and prostatitis, benign prostate hyperplasia, and prostate cancer is analyzed. If 16 is taken as the cut of number for leucocyte presence, its sensitivity is 0.92 (AUC = 0.78 p = 0.01). Conclusions: The number of leucocytes in expressed prostatic secretion is higher in the chronic prostatitis group. If the leukocyte presence of 16 and above is taken as the cut off point, the sensitivity becomes 0.92 (AUC = 0.78). We firmly believe that our new cut off value may be used as to aid prostate specific antigen and derivates while giving biopsy decision.
A 30-year journey from volume-regulated anion currents to molecular structure of the LRRC8 channel

The swelling-activated anion channel VRAC has fascinated and frustrated physiologists since it was first described in 1988. Multiple laboratories have defined VRAC’s biophysical properties and have shown that it plays a central role in cell volume regulation and possibly other fundamental physiological processes. However, confusion and intense controversy surrounding the channel’s molecular identity greatly hindered progress in the field for >15 yr. A major breakthrough came in 2014 with the demonstration that VRAC is a heteromeric channel encoded by five members of the Lrrc8 gene family, Lrrc8A–E. A mere 4 yr later, four laboratories described cryo-EM structures of LRRC8A homomeric channels. As the melee of structure/function and physiology studies begins, it is critical that this work be framed by a clear understanding of VRAC biophysics, regulation, and cellular physiology as well as by the field’s past confusion and controversies. That understanding is essential for the design and interpretation of structure/function studies, studies of VRAC physiology, and studies aimed at addressing the vexing problem of how the channel detects cell volume changes. In this review we discuss key aspects of VRAC biophysics, regulation, and function and integrate these into our emerging understanding of LRRC8 protein structure/function.
The kinetic mechanisms of fast-decay red-fluorescent genetically encoded calcium indicators

Genetically encoded calcium indicators (GECIs) are useful reporters of cell-signaling, neuronal, and network activities. We have generated novel fast variants and investigated the kinetic mechanisms of two recently developed red-fluorescent GECIs (RGECIs), mApple-based jRGECO1a and mRuby-based jRCaMP1a. In the formation of fluorescent jRGECO1a and jRCaMP1a complexes, calcium binding is followed by rate-limiting isomerization. However, fluorescence decay of calcium-bound jRGECO1a follows a different pathway from its formation: dissociation of calcium occurs first, followed by the peptide, similarly to GCaMP-s. In contrast, fluorescence decay of calcium-bound jRCaMP1a occurs by the reversal of the on-pathway: peptide dissociation is followed by calcium. The mechanistic differences explain the generally slower off-kinetics of jRCaMP1a-type indicators compared with GCaMP-s and jRGECO1a-type GECI: the fluorescence decay rate of f-RCaMP1 was 21 s−1, compared with 109 s−1 for f-RGECO1 and f-RGECO2 (37 °C). Thus, the CaM–peptide interface is an important determinant of the kinetic responses of GECIs; however, the topology of the structural link to the fluorescent protein demonstrably affects the internal dynamics of the CaM–peptide complex. In the dendrites of hippocampal CA3 neurons, f-RGECO1 indicates calcium elevation in response to a 100 action potential train in a linear fashion, making the probe particularly useful for monitoring large-amplitude, fast signals, e.g. those in dendrites, muscle cells, and immune cells.
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: Clinical and imaging characteristics

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare white matter degenerative disease characterized by both axonal and glial injury due to a defect in the CSF1R gene. In this report, we describe ALSP in a previously healthy 40-year-old woman presenting with insidiously progressive confusion, memory loss, and loss of social inhibitions. Characteristic magnetic resonance imaging findings for ALSP elucidated the diagnosis, including chronic foci of diffusion restriction in a non-vascular distribution, lack of temporal/infratentorial involvement, cortical sparing, and lack of enhancement. CSF1R genetic testing further confirmed the diagnosis and the patient underwent supportive medical management for symptom control. ALSP can pose a unique diagnostic challenge given its particular adult-onset presentation, but early recognition is key given the poor prognosis and the potential for family genetic testing.
Cardiac Networks United: an integrated paediatric and congenital cardiovascular research and improvement network

Abstract Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.
New Insights into the Interplay between Non-Coding RNAs and RNA-Binding Protein HnRNPK in Regulating Cellular Functions

The emerging data indicates that non-coding RNAs (ncRNAs) epresent more than the “junk sequences” of the genome. Both miRNAs and long non-coding RNAs (lncRNAs) are involved in fundamental biological processes, and their deregulation may lead to oncogenesis and other diseases. As an important RNA-binding protein (RBP), heterogeneous nuclear ribonucleoprotein K (hnRNPK) is known to regulate gene expression through the RNA-binding domain involved in various pathways, such as transcription, splicing, and translation. HnRNPK is a highly conserved gene that is abundantly expressed in mammalian cells. The interaction of hnRNPK and ncRNAs defines the novel way through which ncRNAs affect the expression of protein-coding genes and form autoregulatory feedback loops. This review summarizes the interactions of hnRNPK and ncRNAs in regulating gene expression at transcriptional and post-transcriptional levels or by changing the genomic structure, highlighting their involvement in carcinogenesis, glucose metabolism, stem cell differentiation, virus infection and other cellular functions. Drawing connections between such discoveries might provide novel targets to control the biological outputs of cells in response to different stimuli.
Outcomes of Localized Esophageal Squamous Cell Carcinoma Patients Treated With Definitive Concurrent Chemoradiotherapy Using Either Standard or High Radiotherapy Dose: A Retrospective Study Controlling for Organ at Risk Dose

Background/Aim: The optimal radiotherapy dose for localized esophageal squamous cell carcinoma (ESqCC) patients treated with definitive concurrent chemo-radiotherapy (CCRT) is debated. The aim of our study was to compare patient outcomes using either standard or high radiotherapy dose. Materials and Methods: Eligible patients diagnosed between 2011 and 2015 from the cancer registry of our Institute were identified and a propensity score (PS)-matched cohort (1:1 for high vs. standard dose) was constructed to balance observable potential confounders (including organ at risk dose). The hazard ratio (HR) of death between high and standard dose was compared. Results: Our study population included 73/36 patients before/after PS matching. The HR of death at the high dose compared to the standard dose was 0.554 (95% confidence interval (CI)=0.308-0.998, p=0.049). Conclusion: Definitive CCRT using a high radiotherapy dose showed improved survival outcomes for localized ESqCC patients compared to standard dose.