Miracle-dz/UniFAR-FTUs huggingface dataset:
Intestinal iron absorption is appropriately modulated to match physiological demand for iron in wild-type and iron-loaded Hamp (hepcidin) knockout rats during acute colitis

Mucosal damage, barrier breach, inflammation, and iron-deficiency anemia (IDA) typify ulcerative colitis (UC) in humans. The anemia in UC appears to mainly relate to systemic inflammation. The pathogenesis of this ‘anemia of inflammation’ (AI) involves cytokine-mediated transactivation of hepatic Hamp (encoding the iron-regulatory hormone, hepcidin). In AI, high hepcidin represses iron absorption (and iron release from stores), thus lowering serum iron, and restricting iron for erythropoiesis (causing anemia). In less-severe disease states, inflammation may be limited to the intestine, but whether this perturbs iron homeostasis is uncertain. We hypothesized that localized gut inflammation will increase overall iron demand (to support the immune response and tissue repair), and that hepatic Hamp expression will decrease in response, thus derepressing (i.e., enhancing) iron absorption. Accordingly, we developed a rat model of mild, acute colitis, and studied iron absorption and homeostasis. Rats exposed (orally) to DSS (4%) for 7 days had intestinal (but not systemic) inflammation, and biomarker analyses demonstrated that iron utilization was elevated. Iron absorption was enhanced (by 2-3-fold) in DSS-treated, WT rats of both sexes, but unexpectedly, hepatic Hamp expression was not suppressed. Therefore, to gain a better understanding of regulation of iron absorption during acute colitis, Hamp KO rats were used for further experimentation. The severity of DSS-colitis was similar in Hamp KOs as in WT controls. In the KOs, increased iron requirements associated with the physiological response to colitis were satisfied by mobilizing hepatic storage iron, rather than by increasing absorption of enteral iron (as occurred in WT rats). In conclusion then, in both sexes and genotypes of rats, iron absorption was appropriately modulated to match physiological demand for dietary iron during acute intestinal inflammation, but regulatory mechanisms may not involve hepcidin.
Cystic fibrosis transmembrane conductance regulator-related male infertility: Relevance of genetic testing & counselling in Indian population

Background & objectives: Due to limited information available on the frequency and spectrum of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutations in congenital bilateral absence of vas deferens (CBAVD) in Indian population, it is difficult to provide accurate genetic counselling to couples. The present study was undertaken to investigate the spectrum and frequency of CFTR gene mutations in Indian men with CBAVD and to determine the female CF carrier status. Methods: Direct DNA sequencing of the CFTR gene was carried out in eighty CBAVD men, their female partners and fifty controls from the general population. Pathological significance of the identified novel CFTR gene variants was carried out using in silico tools. Appropriate genetic counselling was provided to the couples prior to intracytoplasmic sperm injection (ICSI). Results: A significant association was observed for CFTR gene variants in Indian CBAVD men versus controls (odds ratio: 12.1; 95% confidence interval: 4.8-30.4; P<0.0001). A total of 20 CFTR gene variants were identified in 53 CBAVD men. Eight novel missense CFTR gene variants (L214V, A238P, E379V, L578I, F587L, L926W, R1325K and R1453Q); two novel splice-site gene variants (c.1-30C>G and IVS1+2T>G) and ten previously reported mutations (R75Q, c.1210-12[5], F508del, A309G, R334W, I444T, R668C, R709X, A1285V and Q1352H) were detected in CBAVD men. The novel and reported CFTR gene mutations were L926W (2.5%, P=0.26), R1453Q (2.5%, P=0.26), F508del (8.75%, P=0.03) and c.1210-12[5] (42.5%, P=0.002). A total of 13 (16.2%) female partners were found to be a CF carrier. Nine couples had a risk of transmitting mutant CFTR allele to the offspring. Interpretation & conclusions: The heterogeneous spectrum of CFTR gene in Indian population suggests the necessity of screening CBAVD men and female partners for accurate genetic counselling prior to undergoing ICSI.
Bottom‐up and top‐down proteomic approaches for the identification, characterization, and quantification of the low molecular weight proteome with focus on short open reading frame‐encoded peptides

The recent discovery of alternative open reading frames creates a need for suitable analytical approaches to verify their translation and to characterize the corresponding gene products at the molecular level. As the analysis of small proteins within a background proteome by means of classical bottom‐up proteomics is challenging, method development for the analysis of small open reading frame encoded peptides (SEPs) have become a focal point for research. Here, we highlight bottom‐up and top‐down proteomics approaches established for the analysis of SEPs in both pro‐ and eukaryotes. Major steps of analysis, including sample preparation and (small) proteome isolation, separation and mass spectrometry, data interpretation and quality control, quantification, the analysis of post‐translational modifications, and exploration of functional aspects of the SEPs by means of proteomics technologies are described. These methods do not exclusively cover the analytics of SEPs but simultaneously include the low molecular weight proteome, and moreover, can also be used for the proteome‐wide analysis of proteolytic processing events.
Genome‐wide association mapping of seedling and adult plant response to stem rust in a durum wheat panel

Many of the major stem rust resistance genes deployed in commercial wheat (Triticum spp.) cultivars and breeding lines become ineffective over time because of the continuous emergence of virulent races. A genome‐wide association study (GWAS) was conducted using 26,439 single nucleotide polymorphism (SNP) markers and 280 durum wheat [Triticum turgidum L. subsp. Durum (Desf.) Husnot] lines from CIMMYT to identify genomic regions associated with seedling resistance to races TTKSK, TKTTF, JRCQC, and TTRTF and field resistance to TKTTF and JRCQC. The phenotypic data analysis across environments revealed 61–91 and 59–77% of phenotypic variation was explained by the genotypic component for seedling and adult plant response of lines, respectively. For seedling resistance, mixed linear model (MLM) identified eight novel and nine previously reported quantitative trait loci (QTL) while a fixed and random model circulating probability unification (FarmCPU) detected 12 novel and eight previously reported QTL. For field resistance, MLM identified 12 novel and seven previously reported loci while FarmCPU identified seven novel and nine previously reported loci. The regions of Sr7a, Sr8155B1, Sr11, alleles of Sr13, Sr17, Sr22/Sr25, and Sr49 were identified. Novel loci on chromosomes 3B, 4A, 6A, 6B, 7A, and 7B could be used as sources of resistance to the races virulent on durum wheat. Two large‐effect markers on chromosome 6A could potentially be used to differentiate resistant haplotypes of Sr13 (R1 and R3). Allelism tests for Sr13, breaking the deleterious effect associated with Sr22/Sr25 and retaining the resistance allele at the Sr49 locus, are needed to protect future varieties from emerging races.
Psychological wellbeing and mental health amongst medical undergraduates: A descriptive study assessing more than 1,000 medical students in Sri Lanka

Background: Studies from around the world have shown higher rates of anxiety, depression, alcohol and other drug use, and burnout in medical students. Aims: The aim of this study was to identify the socio-demographic factors and severity of difficulties Sri Lankan medical students face regarding psychological wellbeing and burnout. Method: This one-off survey used a cross-sectional design, assessing substance use, psychological wellbeing, and burnout using the CAGE, GHQ-12, and OLBI. The survey was open to all medical students in six universities in Sri Lanka. Chi-square analysis was used to assess the statistical significance related to categorical dependent variables and one-way ANOVA for continuous dependent variables. Results: A higher prevalence of diagnosed mental health conditions was found following admission to the medical course in comparison prior to admission. Sixty-two percent of students had a score of more than 2 on the GHQ-12 indicating caseness. The OLBI identified exhaustion in 79% of students. The CAGE questionnaire was positive in 4.8% of students. Conclusions: Only a small proportion of students are recognizing their mental health difficulties and seeking help. Further understanding is required as to why this is, as well as re-evaluation of the demands of the curriculum. Effective ways of regularly identifying and providing practical and evidence-based support for mental health problems in medical and other undergraduates need to be identified and introduced.
Advanced donor age does not increase risk of hepatocellular carcinoma recurrence after liver transplantation: a retrospective two‐centre analysis using competing risk analysis

The impact of donor age on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation is still debated. Between 2002 and 2014, all patients transplanted for HCC in 2 European liver transplantation tertiary centres were retrospectively reviewed. Risk factors for HCC recurrence were assessed using competing risk analysis, and the impact of donor age < or ≥65 years and < or ≥80 years was specifically evaluated after propensity score matching. 728 patients transplanted with a median follow‐up of 86 months were analysed. The 1‐, 3‐ and 5‐year recurrence rates were 4.9%, 10.7% and 13.9%, respectively. In multivariable analysis, recipient age (sHR: 0.96 [0.93; 0.98], P < 0.01), number of lesions (sHR: 1.05 [1.04; 1.06], P < 0.001), maximum size of the lesions (sHR: 1.37 [1.27; 1.48], P < 0.01), presence of a hepatocholangiocarcinoma (sHR: 6.47 [2.91; 14.38], P < 0.01) and microvascular invasion (sHR: 3.48 [2.42; 5.02], P < 0.01) were significantly associated with HCC recurrence. After propensity score matching, neither donor age ≥65 (P = 0.29) nor donor age ≥80 (P = 0.84) years increased the risk of HCC recurrence. In conclusion, donor age was not found to be a risk factor for HCC recurrence. Patients listed for HCC can receive a graft from an elderly donor without compromising the outcome.
Long‐term cognitive and psychosocial outcomes in adults with phenylketonuria

Previous studies have suggested that cognitive and psychosocial underfunctioning in early‐treated adults with phenylketonuria (PKU) may be explained by suboptimal adherence to dietary treatments, however, these studies often employ small samples, with different outcome measures, definitions and cut‐offs. Samples have also tended to comprise participants with a limited range of blood phenylalanine concentrations, and often individuals who may not have been treated early enough to avoid neurological damage. In this study, we explore the impact of lifetime dietary control, as indicated by blood phenylalanine concentrations in childhood, adolescence and adulthood, on long‐term cognitive and psychosocial outcomes in a large sample of adults with PKU who were diagnosed by neonatal screening and commenced on dietary treatment within the first month of life. One hundred and fifty‐four participants underwent cognitive testing, assessing attention, learning, working memory, language, executive functioning and processing speed. One hundred and forty‐nine completed measures of psychosocial functioning, documenting educational, occupational, quality of life, emotional and social outcomes which were compared with a group of healthy controls. Many adults with PKU demonstrated cognitive impairments, most frequently affecting processing speed (23%), executive function (20%) and learning (12%). Cognitive outcomes were related to measures of historic metabolic control, but only processing speed was significantly related to phenylalanine concentration at the time of testing after controlling for historic levels. Adults with PKU did not, however, differ from controls in educational, occupational, quality of life or emotional outcomes, or on a measure of family functioning, and showed only minor differences in relationship style. These findings have implications for patient counselling and decisions regarding the management of PKU in adulthood.
Outcomes of Tibiotalocalcaneal Arthrodesis with a Femoral Nail.

BACKGROUND Retrograde intramedullary nailing for tibiotalocalcaneal arthrodesis (TTCA) is used for severe hindfoot deformities, end-stage arthritis, and limb salvage. The procedure is technically demanding, with complications such as infection, hardware failure, nonunion, osteomyelitis, and possible limb loss or death. This study reports the outcomes and complications of patients undergoing TTCA with a femoral nail, which is widely available and offers an extensive range of lengths and diameters. METHODS We performed a retrospective review of 104 patients who underwent 109 TTCAs using a femoral nail as the primary procedure (January 2006 through December 2016). Demographic data, risk factors, and outcomes were evaluated. RESULTS At final follow-up, the overall clinical union rate was 89 of 109 (81.7%). Diabetes mellitus was negatively associated with limb salvage (P = .03), and peripheral neuropathy (P = .02) and Charcot's neuroarthropathy (P = .03) were negatively associated with clinical union. Only four patients (3.8%) underwent proximal amputation, at an average of 6.1 months, and 11 patients (10.6%) died, at a mean of 38.0 months. The most common complication was ulceration in 27 of 109 limbs (24.8%), followed by infection in 25 (22.9%). Twenty-three patients (22.1%) underwent revision procedures, at a mean of 9.4 months. Thirteen of these 23 patients (56.5%) had antibiotic cement rod spacers/rods for deep infection-related complications. CONCLUSIONS Use of a femoral nail has been shown to provide similar outcomes and limb salvage rates compared with other methods of TTCA reported for similar indications in the literature.
Synthesis of iron(III)-urea complex in organic solvent and its thermal decomposition

In this work,iron(Ⅲ)-urea complex was synthesized in ethanol.The results of elemental analysis and Fourier transform infrared(FT-IR) spectroscopy suggested that the composition of resulting complex was [Fe(CON2H4)6](NO3)3.The thermal decomposition mechanism and product of the [Fe(CON2H4)6](NO3)3 were studied by using differential thermal analysis(DTA),thermogravimetric(TG) method,and X-ray powder diffractometry(XRD). Thermal analyses suggested that the thermal decomposition of the complex occurred through a two-stage decomposition mechanism.The result of XRD showed that the product of thermal decomposition of the complex was γ-Fe2O3.
Progressive Neurodegeneration Across Chronic Stages of Severe Traumatic Brain Injury

Objective: To examine the trajectory of structural gray matter changes across 2 chronic periods of recovery in individuals who have sustained severe traumatic brain injury (TBI), adding to the growing literature indicating that neurodegenerative processes occur in the months to years postinjury. Participants: Patients who experienced posttraumatic amnesia of 1 hour or more, and/or scored 12 or less on the Glasgow Coma Scale at the emergency department or the scene of the accident, and/or had positive brain imaging findings were recruited while receiving inpatient care, resulting in 51 patients with severe TBI. Methods: Secondary analyses of gray matter changes across approximately 5 months, 1 year, and 2.5 years postinjury were undertaken, using an automated segmentation protocol with improved accuracy in populations with morphological anomalies. We compared patients and matched controls on regions implicated in poorer long-term clinical outcome (accumbens, amygdala, brainstem, hippocampus, thalamus). To model brain-wide patterns of change, we then conducted an exploratory principal component analysis (PCA) on the linear slopes of all regional volumes across the 3 time points. Finally, we assessed nonlinear trends across earlier (5 months-1 year) versus later (1-2.5 years) time-windows with PCA to compare degeneration rates across time. Chronic degeneration was predicted cortically and subcortically brain-wide, and within specific regions of interest. Results: (1) From 5 months to 1 year, patients showed significant degeneration in the accumbens, and marginal degeneration in the amygdala, brainstem, thalamus, and the left hippocampus when examined unilaterally, compared with controls. (2) PCA components representing subcortical and temporal regions, and regions from the basal ganglia, significantly differed from controls in the first time-window. (3) Progression occurred at the same rate across both time-windows, suggesting neither escalation nor attenuation of degeneration across time. Conclusion: Localized yet progressive decline emphasizes the necessity of developing interventions to offset degeneration and improve long-term functioning.
Factors Associated With Frailty in Patients Undergoing Cardiac Surgery

Background Frailty may increase the risk of complications and mortality in patients undergoing cardiac surgery. Few studies on frailty and its associated factors have been conducted in these patients. Objective The aim of this study was to explore frailty and related factors in patients undergoing cardiac surgery. Methods A total of 154 patients undergoing cardiac surgery in northern Taiwan were recruited using a longitudinal study design and interviewed using structured questionnaires assessing physical activity, anxiety and depression, and social support before surgery and at 1 month and 3 months after surgery. Results The prevalence of frailty in patients undergoing cardiac surgery was 16.2%, 20.5%, and 16.6% before surgery and at 1 month and 3 months after surgery, respectively. Frail and prefrail patients undergoing cardiac surgery were more likely to be unemployed, have gout, have a higher New York Heart Association class, have preoperative dysrhythmia, undergo cardiopulmonary bypass, have a lower functional ability, have a higher European System for Cardiac Operative Risk Evaluation score, have a longer anesthesia time, have longer endotracheal tube and extracorporeal circulation times, have longer intensive care unit and hospital stays, have lower hemoglobin and albumin levels, have higher anxiety and depression levels, and have lower Mini-Mental State Examination scores. The significant predictors of prefrailty and frailty included unemployment, the presence of gout, higher New York Heart Association classes, less independence in activities of daily living, lower hemoglobin levels, and higher levels of depression. Conclusions Frailty was associated with patients' functional status, perioperative conditions and psychosocial factors. Preoperative assessments of frailty and appropriate interventions are needed to improve frailty in patients undergoing cardiac surgery.
Asleep or awake motor mapping for resection of perirolandic glioma in the nondominant hemisphere? Development and validation of a multimodal score to tailor the surgical strategy.

OBJECTIVE Resection of glioma in the nondominant hemisphere involving the motor areas and pathways requires the use of brain-mapping techniques to spare essential sites subserving motor control. No clear indications are available for performing motor mapping under either awake or asleep conditions or for the best mapping paradigm (e.g., resting or active, high-frequency [HF] or low-frequency [LF] stimulation) that provides the best oncological and functional outcomes when tailored to the clinical context. This work aimed to identify clinical and imaging factors that influence surgical strategy (asleep motor mapping vs awake motor mapping) and that are associated with the best functional and oncological outcomes and to design a "motor mapping score" for guiding tumor resection in this area. METHODS The authors evaluated a retrospective series of patients with nondominant-hemisphere glioma-located or infiltrating within 2 cm anteriorly or posteriorly to the central sulcus and affecting the primary motor cortex, its fibers, and/or the praxis network-who underwent operations with asleep (HF monopolar probe) or awake (LF and HF probes) motor mapping. Clinical and imaging variables were used to design a motor mapping score. A prospective series of patients was used to validate this motor mapping score. RESULTS One hundred thirty-five patients were retrospectively analyzed: 69 underwent operations with asleep (HF stimulation) motor mapping, and 66 underwent awake (LF and HF stimulation and praxis task evaluation) motor mapping. Previous motor (strength) deficit, previous treatment (surgery/radiotherapy), tumor volume > 30 cm3, and tumor involvement of the praxis network (on MRI) were identified and used to design the mapping score. Motor deficit, previous treatment, and location within or close to the central sulcus favor use of asleep motor mapping; large tumor volume and involvement of the praxis network favor use of awake motor mapping. The motor mapping score was validated in a prospective series of 52 patients-35 underwent operations with awake motor mapping and 17 with asleep motor mapping on the basis of the score indications-who had a low rate of postoperative motor-praxis deficit (3%) and a high extent of resection (median 97%; complete resection in > 70% of patients). CONCLUSIONS Extensive resection of tumor involving the eloquent areas for motor control is feasible, and when an appropriate mapping strategy is applied, the incidence of postoperative motor-praxis deficit is low. Asleep (HF stimulation) motor mapping is preferable for lesions close to or involving the central sulcus and/or in patients with preoperative strength deficit and/or history of previous treatment. When a patient has no motor deficit or previous treatment and has a lesion (> 30 cm3) involving the praxis network, awake mapping is preferable.
Quality of Neurologic Care in the United States

Objective To provide the initial description of the quality of outpatient US neurologic care as collected and reported in the Axon Registry. Methods We describe characteristics of registry participants and the performance of neurology providers on 20 of the 2019 Axon Registry quality measures. From the distribution of providers' scores on a quality measure, we calculate the median performance for each quality measure. We test for associations between quality measure performance, provider characteristics, and intrinsic measure parameters. Results There were 948 neurology providers who contributed a total of 6,480 provider-metric observations. Overall, the average quality measure performance score at the provider level was 66 (median 77). At the measure level (n = 20), the average quality measure performance score was 53 (median 55) with a range of 2 to 100 (interquartile range 20–91). Measures with a lower-complexity category (e.g., discrete orders, singular concepts) or developed through the specialty's qualified clinical data registry pathway had higher performance distributions. There was no difference in performance between Merit-Based Incentive Payment System (MIPS) and non-MIPS providers. There was no association between quality measure performance and practice size, measure clinical topic/neurologic condition, or measure year of entry. Conclusions This cross-sectional assessment of quality measure performance in 2019 Axon Registry data demonstrates modest performance scores and considerable variability across measures and providers. More complex measures were associated with lower performance. These findings serve as a baseline assessment of quality of ambulatory neurologic care in the United States and provide insights into future measure design.