Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA J homolog subfamily B member 9 and other advances in fibrillary glomerulonephritis

Purpose of review Fibrillary glomerulonephritis (FGN) involves ∼1% of native kidney biopsies and is characterized by glomerular deposition of fibrils larger than amyloid (12–24 nm diameter) composed of polyclonal immunoglobulin G (IgG). The recent discovery of DNA J homolog subfamily B member 9 (DNAJB9) in FGN glomerular deposits has contributed a specific and sensitive biomarker, informing morphologic classification and pathogenesis. This review will consider contemporary FGN incidence and genetics, pathogenesis, (lack of) paraprotein association, variants, treatment, and transplantation. Recent findings DNAJB9 tissue assays have enabled the identification of morphologic variants and improved classification of fibrillary-like glomerular diseases. Together with paraffin immunofluorescence and IgG subclass studies, these have established that FGN is only rarely monoclonal and these patients usually do not have an monoclonal gammopathy. The discovery of DNAJB9 opens new avenues of investigation into FGN pathogenesis, especially those of the unfolded protein response. Treatment for FGN remains empiric, with some encouraging data on rituximab-based therapy. Transplantation is a good option for patients progressing to end-stage kidney disease. Summary Advances building on the discovery of DNAJB9 in FGN should lead to long-term evolution in targeted treatment and outcome of this glomerular disease.
Predictors of UK healthcare worker burnout during the COVID-19 pandemic

Summary Background The COVID-19 pandemic is putting health professionals under increasing pressure. This population is already acknowledged to be at risk of burnout. Aim We aim to provide a ‘snapshot’ of the levels of burnout, anxiety, depression and distress among healthcare workers during the COVID-19 pandemic. Methods We distributed an online survey via social media in June 2020 open to any UK healthcare worker. The primary outcome measure was symptoms of burnout measured using the Copenhagen Burnout Inventory. Secondary outcomes of depression, anxiety, distress and subjective measures of stress were also recorded. Multivariate logistic regression analysis was performed to identify factors associated with burnout, depression, anxiety and distress. Results A total of 539 persons responded to the survey; 90% female and 53% nurses. Participants with moderate-to-severe burnout were younger (49% vs. 33% under 40 years, P = 0.004), more likely to have pre-existing comorbidities (21% vs. 12%, P = 0.031), twice as likely to have been redeployed from their usual role (22% vs. 11%; P = 0.042), or to work in an area dedicated to COVID-19 patients (50% vs. 32%, P < 0.001) and were almost 4 times more likely to have previous depression (24% vs. 7%; P = 0.012). Conclusion Independent predictors of burnout were being younger, redeployment, exposure to patients with COVID-19, being female and a history of depression. Evaluation of existing psychological support interventions is required with targeted approaches to ensure support is available to those most at risk.
Medial septal GABAergic neurons reduce seizure duration upon optogenetic closed-loop stimulation

Abstract Seizures can emerge from multiple or large foci in temporal lobe epilepsy, complicating focally targeted strategies such as surgical resection or the modulation of the activity of specific hippocampal neuronal populations through genetic or optogenetic techniques. Here, we evaluate a strategy in which optogenetic activation of medial septal GABAergic neurons, which provide extensive projections throughout the hippocampus, is used to control seizures. We utilized the chronic intrahippocampal kainate mouse model of temporal lobe epilepsy, which results in spontaneous seizures and as is often the case in human patients, presents with hippocampal sclerosis. Medial septal GABAergic neuron populations were immunohistochemically labelled and were not reduced in epileptic conditions. Genetic labelling with mRuby of medial septal GABAergic neuron synaptic puncta and imaging across the rostral to caudal extent of the hippocampus, also indicated an unchanged number of putative synapses in epilepsy. Furthermore, optogenetic stimulation of medial septal GABAergic neurons consistently modulated oscillations across multiple hippocampal locations in control and epileptic conditions. Finally, wireless optogenetic stimulation of medial septal GABAergic neurons, upon electrographic detection of spontaneous hippocampal seizures, resulted in reduced seizure durations. We propose medial septal GABAergic neurons as a novel target for optogenetic control of seizures in temporal lobe epilepsy.
Effect of two phytases at two doses on performance and phytate degradation in broilers during 1–21 days of age

The effect of two microbial phytases at two dose-levels on performance and apparent ileal digestibility (AID) of nutrients in broilers fed European-type diets was studied. A total of 1,200 d-old Ross 308 male broilers were randomly assigned to 5 treatments with 30 birds/pen and 8 pens/treatment. A nutritionally adequate positive control (PC) diet was tested against 4 experimental diets containing reduced total P, retainable P, Ca and Na as per the recommended nutritional contribution for Buttiauxella phytase (Phy B) at 1,000 FTU/kg (-1.87 g/kg, -1.59 g/kg, -1.99 g/kg and -0.4 g/kg vs. PC, respectively). Experimental diets were supplemented with Phy B at 500 FTU/kg or 1,000 FTU/kg, or Citrobacter phytase (Phy C) at 1,000 FTU/kg or 2,000 FTU/kg. Diets were based on corn, soybean meal, rapeseed meal and sunflower meal and formulated by phase (starter 1–10 d, grower 11–21 d) in crumbled or pelleted form. Overall (d 1–21), at 1,000 FTU/kg, birds fed Phy C exhibited lower BWG (-2.7%), FI (-3.4%) and tibia ash (-2.2%) vs. PC (P < 0.05), and reduced BWG (-3.6%), FI (-3.9%) and tibia ash (-1.8%) vs. Phy B (P < 0.05). Phy B at 1,000 FTU/kg and Phy C at 2,000 FTU/kg maintained performance equivalent to the PC. Digestibility of Ca did not differ among phytase treatments but at 1,000 FTU/kg AID P was greater with Phy B than Phy C (72.3% vs. 62.7%, P < 0.05). Ileal phytate (myo-inositol hexakisphosphate, IP6) digestibility was greatest with Phy B at 1,000 FTU/kg which was higher than Phy C at 1,000 FTU/kg (87.6 vs. 60.6%, P < 0.05). The findings indicate a higher phytate degradation rate of Phy B than Phy C at equivalent dose-level and this is correlated to the performance of the broilers.
Influence of food hydrocolloids on the structural, textural and chemical characteristics of low-fat banana chips

Banana chips are gaining popularity as a deep-fried product for its unique taste and flavour. This study is aimed to investigate the effect of hydrocolloids on oil absorption, physico-chemical and sensory properties of banana chips from two different varieties (var. Popoulu and var. Nendran), when fried at 180 °C for 3 min. The reduction in oil content was about 15%–35% and 19%–30% for hydrocolloid treated Popoulu and Nendran chips, respectively. The Free fatty acid content (FFA) of hydrocolloid treated banana chips was lower than that of untreated chips. The peroxide value (PV) values of all samples fell below 2 meq oxygen kg−1. CMC pre-treated banana chips were crispier than other formulations on both the varieties. Microscopic analysis showed the improved cellular integrity without large void spaces in hydrocolloid treated banana chips. PCA analyses elucidated that variables such as physical appearance, colour, crispiness, after taste, overall acceptability contributed positively, whereas hardness and sogginess contributed negatively to the correlation among the variables. From the chemical and sensory attributes, 0.5% CMC treated Popoulu chips and 1% CMC treated Nendran chips is recommended to produce chips with lower oil content.
Dissolution Morphology of Iron (Oxy)(Hydr)Oxides Exposed to the Dissimilatory Iron-Reducing Bacterium Shewanella oneidensis MR-1

Atomic force microscopy was used to compare the dissolution morphology of iron (oxy)(hydr)oxide coated slides exposed to the dissimilatory iron reducing bacterium Shewanella oneidensis MR-1 and a Type II protein secretion mutant unable to reduce iron minerals without an exogenous electron shuttle. Dissolution morphologies of slides exposed to the wild-type organism were heterogeneous and consistent with the morphology of bacterial microcolonies observed by confocal microscopy. In contrast, dissolution morphologies of slides exposed to wild-type or mutant strains and the electron shuttling compound 9,10-anthraquinone-2,6-disulfonate were homogeneous. These results suggest that microcolony formation by the wild-type strain may limit dissolution whereas respiration using the shuttle compound relieves this limitation.
Twist1 signaling in age-dependent decline in angiogenesis and lung regeneration

Angiogenesis – the formation of new blood capillaries- is impaired in aging animals and contributes to the pathogenesis of age-related diseases. A transcription factor, Twist1, contributes to the pathogenesis of age- and angiogenesis-related diseases such as pulmonary fibrosis and atherosclerosis. However, the mechanism by which Twist1 controls age-dependent decline in angiogenesis remains unclear. In this report, we have demonstrated that the levels of Twist1 are higher, while the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) that stimulates angiogenesis, is lower in endothelial cells (ECs) isolated from aged human adipose tissues and mouse lungs compared to those from young tissues. Knockdown of Twist1 in aged human ECs increases the levels of PGC1α and angiogenic factor receptor, vascular endothelial growth factor receptor (VEGFR2), and restores EC proliferation and migration, while inhibition of PGC1α suppresses these effects. Knockdown of Twist1 in supplemented aged ECs also restores vascular networks in the subcutaneously implanted gel, while these effects are abrogated by knockdown of PGC1α. Age-dependent inhibition of post-pneumonectomy (PNX) lung growth is suppressed in Tie2-specific Twist1 conditional knockout mouse lungs, in which VEGFR2 expression increases after PNX. These results suggest that upregulation of endothelial Twist1 mediates age-dependent decline in angiogenesis and regenerative lung growth.
Orbital-Free Quantum Crystallographic View on Noncovalent Bonding: Insights into Hydrogen Bonds, π∙∙∙π and Reverse Electron Lone Pairs∙∙∙π Interactions.

A detailed analysis of a complete set of the local potentials that appear in the Euler equation for electron density is carried out for noncovalent interactions in the crystal of a uracil derivative using experimental X-ray charge density. The interplay between the quantum theory of atoms in molecules and crystals and the local potentials and corresponding inner-crystal electronic forces of electrostatic and kinetic origin is explored. Partitioning of crystal space into atomic basins and atomic-like potential basins led us to the definite description of interatomic interaction and charge transfer. Novel physically grounded bonding descriptors derived within the orbital-free quantum crystallography provided the detailed examination of π-stacking and intricate C=O∙∙∙π interactions and nonclassical hydrogen bonds present in the crystal. The donor-acceptor character of these interactions is revealed by analysis of Pauli and von Weizsäcker potentials together with well-known functions, e.g., deformation electron density and electron localization function. In this way, our analysis throws light on aspects of these closed-shell interactions hitherto hidden from the description.
Conditions for coalescence of multiple electric discharges

Separate and coalesced electric discharges have been studied and the conditions for coalescence analysed. The discharges coalesce to operate at the minimum voltage, if this is not a minimum they will remain uncoalesced. The results are supportive evidence for Steenbeck's minimum potential principle. A model of a coalesced discharge is proposed and the principle conditions necessary for coalescence are given.
Prolonged Capillary Refilling as a Predictor of Mortality in Patients With Septic Shock

Introduction: Microcirculatory alterations characterize septic shock; increased blood lactate level has been described as markers of microcirculation alteration in patients with septic shock. Although useful, this serological analysis is not always feasible in all settings worldwide. Objective: To determine if a prolonged capillary refilling is a predictor of mortality in patients with septic shock. Methodology: A 10-months prospective cohort study was carried out on 175 patients admitted to the Intensive Care Unit (ICU) with the diagnosis of septic shock. The capillary refilling time (CRT) was evaluated Immediately upon admission and after 6 hours post-resuscitation. Traditional tissue perfusion markers were also used to compare and analyze their predictive value on mortality at 28 days. Results: The area under the ROC curve (AUC) to estimate mortality in patients with septic shock with CRT at admission was 0.666 (0.584-0.748), while at 6 hours was 0.819 (0.753-0.885), with a cut-off point of 4.5 seconds at admission (PPV 52.87% NPV 72.73%) and 3.5 sec at 6 hours (PPV 95.56% NPV 79.23%). In those with CRT > 3.5 seconds at 6 hours, they had a RR of 4.60, while a CRT > 4.5 seconds at admission had a RR of 1.94, with a non-survivor proportion of 95.56% for a CRT > 3.5 sec at 6 hours vs 20.77% for CRT ≤ 3.5 sec (P value < 0.001). The CRT at 6 hours showed significant differences in the survival curves with P-value < 0.001, where for values > 3.5 sec, survival at 28 days was 4.44% vs 79.20% for values ≤ 3.5 sec. Conclusion: CRT is a strong predictor of mortality in patients with septic shock. Evaluating changes in CRT during resuscitation from septic shock might be used as an important clinical tool to predict mortality; especially in low-resources settings where using other biomarkers might be sometimes difficult.
Developmental trajectories of ADHD symptoms in a large population-representative longitudinal study

Abstract Background Previous research has suggested that there is substantial heterogeneity in the developmental trajectories of attention-deficit/hyperactivity disorder (ADHD) symptoms. Sometimes, qualitative distinctions between trajectories with different ages of onset and/or patterns of remission are made; however, little is known about the predictors and broader clinical meaningfulness of these candidate ‘developmental subtypes’ of ADHD symptoms. Methods We applied latent class growth analysis to data from the UK Millennium Cohort Study (MCS; N = 11 316; ages 3, 5, 7, 11 and 14) to evaluate whether developmental trajectories of ADHD symptoms differing in early life predictors could be identified. Our optimal model included six trajectory groups, labelled unaffected (34.9% of the sample), mildly affected (24.1%), subclinical remitting (12.8%), pre-school onset partially remitting (14.1%), developmentally increasing (7.6%) and pre-school onset persistent (6.4%). Results Factors such as gender, conduct problems, cognitive ability, maternal education, premature birth, peer problems and school readiness scores differentiated between specific ADHD symptom trajectories. Conclusions Taken together, our findings provide preliminary evidence that distinguishing different trajectories of ADHD symptoms could be clinically informative.
Metagenomic analysis exploring taxonomic and functional diversity of bacterial communities of a Himalayan urban fresh water lake

Freshwater lakes present an ecological border between humans and a variety of host organisms. The present study was designed to evaluate the microbiota composition and distribution in Dal Lake at Srinagar, India. The non-chimeric sequence reads were classified taxonomically into 49 phyla, 114 classes, 185 orders, 244 families and 384 genera. Proteobacteria was found to be the most abundant bacterial phylum in all the four samples. The highest number of observed species was found to be 3097 in sample taken from least populated area during summer (LPS) whereas the summer sample from highly populated area (HPS) was found most diverse among all as indicated by taxonomic diversity analysis. The QIIME output files were used for PICRUSt analysis to assign functional attributes. The samples exhibited a significant difference in their microbial community composition and structure. Comparative analysis of functional pathways indicated that the anthropogenic activities in populated areas and higher summer temperature, both decrease functional potential of the Lake microbiota. This is probably the first study to demonstrate the comparative taxonomic diversity and functional composition of an urban freshwater lake amid its highly populated and least populated areas during two extreme seasons (winter and summer).
Fast A‐type currents shape a rapidly adapting form of delayed short latency firing of excitatory superficial dorsal horn neurons that express the neuropeptide Y Y1 receptor

Neuropeptide Y Y1 receptor‐expressing neurons in the dorsal horn of the spinal cord contribute to chronic pain. For the first time, we characterized the firing patterns of Y1‐expressing neurons in Y1eGFP reporter mice. Under hyperpolarized conditions, most Y1eGFP neurons exhibited fast A‐type potassium currents and delayed, short‐latency firing (DSLF). Y1eGFP DSLF neurons were almost always rapidly adapting and often exhibited rebound spiking, characteristics of spinal pain neurons under the control of T‐type calcium channels. These results will inspire future studies to determine whether tissue or nerve injury downregulates the channels that underlie A‐currents, thus unmasking membrane hyperexcitability in Y1‐expressing dorsal horn neurons, leading to persistent pain.
Drugging multiple same-allele driver mutations in cancer

Computational Structural Biology Section, Frederick National Laboratory for Cancer Research in the Laboratory of Cancer ImmunoMetabolism, National Cancer Institute, Frederick U.S.A; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University Israel; Computational Structural Biology Section, Laboratory of Cancer ImmunoMetabolism, National Cancer Institute, Frederick USA
Ego effectiveness: A novel individual difference approach to health behavior and coping

Taking care of one’s health can require trading current feelings for longer-term considerations of health and well-being. The present research (total N = 366) sought to assess ego operations of this type in terms of the extent to which the self would be capable of responding to health-challenging situations in ways deemed to be effective. Ego effective individuals engaged in a greater frequency of health-protective behaviors as well as a lesser frequency of risky behaviors, both with respect to a peer protocol (Study 1) and a daily life protocol (Study 2). Findings are informative concerning multiple self-regulation perspectives on health.
A simple physical model of liquid-glass transition : intrinsic fluctuating interactions and random fields hidden in glass-forming liquids

We propose that glass-forming liquids are intrinsically under the influences of both fluctuating interactions and random fields well-known in the field of spin systems. This is due to the frustration between the isotropic and anisotropic parts of effective intermolecular interactions. Our model indicates the existence of two key temperatures relevant to the glass transition, the density ordering point and the Vogel - Fulcher temperature . Between and , a system has features similar to the `Griffiths phase', while below it has those peculiar to the `spin-glass phase'. This picture naturally and universally explains vitrification behaviour from its strong to its fragile limit.
Therapeutic Escape in Gαq-mutant Uveal Melanoma: It's a FAK

Through a synthetic lethal screen, ERK activation was found to mediate resistance to FAK inhibition in GNAQ-mutant uveal melanoma. With PLCB-PKC-ERK and Trio-FAK-Yap representing compensatory effectors of mutant Gαq signaling, combined inhibition of both pathways may be a promising therapeutic strategy in metastatic uveal melanoma. See related article by Paradis et al., p. 3190
Diagnostic accuracy and complication rates of percutaneous CT-guided coaxial needle biopsy of pulmonary lesions.

PURPOSE The aim of this retrospective study was to evaluate and compare diagnostic accuracy and complication rates of percutaneous computed tomography (CT)-guided biopsies of pulmonary lesions 10-35 mm, 35-50 mm, and >50 mm, using the coaxial biopsy technique. METHODS Over a 4-year period, 235 lung biopsies were performed using the coaxial biopsy technique with 18G semi-automated true-cut needle. There were 163 (69.4%) male and 72 (30.6%) female patients, with a mean age of 64.01±9.18 years (18-85 years). The mean lesion size was 59.6±29.3 mm. The lesions were stratified into three groups according to size: lesions <35 mm (n=42, 17.9%), lesions 35-50 mm (n=53, 22.5%), and lesions >50 mm (n=140, 59.6%). Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for all biopsies, and for each group separately, as well as the incidence of complications. RESULTS The overall diagnostic accuracy was 95.4%, with 95.52% sensitivity, 100% specificity, 100% PPV, and 47.37% NPV. For lesions <35 mm, diagnostic accuracy, sensitivity, and PPV were 100%. The lowest diagnostic accuracy was 93.9% in lesions >50 mm, with 93.65% sensitivity, 100% specificity, 100% PPV, and 42.86% NPV. An adequate sample was obtained in 219 core biopsies (93.2%), while 16 biopsies (6.8%) were nondiagnostic due to necrosis (4.25%) and insufficient biopsy material (2.55%). The most frequent complication was minor pneumothorax, which was seen at a rate of 19.1%; pneumothorax requiring chest tube placement occurred in 3 patients (1.3%). CONCLUSION Diagnostic accuracy decreased with increasing lesion size. On the other hand, complication rates were higher in smaller lesions, more distanced from the pleura.
A preliminary study into the use of tree-ring and foliar geochemistry as bio-indicators for vehicular NOx pollution in Malta

ABSTRACT Emissions from traffic over the past few decades have become a significant source of air pollution. Among the pollutants emitted are nitrogen oxides (NOx), exposure to which can be detrimental to public health. Recent studies have shown that nitrogen (N) stable isotope ratios in tree-rings and foliage express a fingerprint of their major N source, making them appropriate for bio-monitoring purposes. In this study, we have applied this proxy to Aleppo pines (Pinus halepensis) at three distances from one of the busiest roads in Malta, a country known to suffer from intense traffic pollution. Our results showed that N and organic carbon (C) stable isotope ratios in tree-rings do not vary over the period 1980–2018 at any of the investigated sites; however, statistically significant spatial trends were apparent in both tree-rings and foliage. The roadside and transitional sites exhibited more positive δ 15N and more negative δ 13C values compared to those at a rural control site. This is likely due to the incorporation of 15N-enriched NOx and 13C-depleted CO2 from traffic pollution. Sampled top-soil also exhibited the δ 15N trend. Our results constitute the first known application of dendrogeochemistry to atmospheric pollution monitoring in Malta.