Miracle-dz/UniFAR-FTUs huggingface dataset:
Tamoxifen administration induces histopathologic changes within the lungs of Cre-recombinase-negative mice: A case report

Tamoxifen is commonly used as a cancer treatment in humans and for inducing genetic alterations using Cre-lox mouse models in the research setting. However, the extent of tamoxifen off-target effects in animal research is underappreciated. Here, we report significant changes in cellular infiltration in Cre-recombinase-negative mice treated with tamoxifen intraperitoneally. These changes were noted in the lungs, which were characterized by the presence of alveolitis, vasculitis, and pleuritis. Despite significant immunological changes in response to tamoxifen treatment, clinical symptoms were not observed. This study provides a cautionary note that tamoxifen treatment alone leads to histologic alterations that may obscure research interpretations and further highlights the need for the development of alternative mouse models for inducible Cre-mediated deletion.
Prophage Tracer: precisely tracing prophages in prokaryotic genomes using overlapping split-read alignment

Abstract The life cycle of temperate phages includes a lysogenic cycle stage when the phage integrates into the host genome and becomes a prophage. However, the identification of prophages that are highly divergent from known phages remains challenging. In this study, by taking advantage of the lysis-lysogeny switch of temperate phages, we designed Prophage Tracer, a tool for recognizing active prophages in prokaryotic genomes using short-read sequencing data, independent of phage gene similarity searching. Prophage Tracer uses the criterion of overlapping split-read alignment to recognize discriminative reads that contain bacterial (attB) and phage (attP) att sites representing prophage excision signals. Performance testing showed that Prophage Tracer could predict known prophages with precise boundaries, as well as novel prophages. Two novel prophages, dsDNA and ssDNA, encoding highly divergent major capsid proteins, were identified in coral-associated bacteria. Prophage Tracer is a reliable data mining tool for the identification of novel temperate phages and mobile genetic elements. The code for the Prophage Tracer is publicly available at https://github.com/WangLab-SCSIO/Prophage_Tracer.
High cholesterol concentrations as well as low cholesterol concentrations are associated with mortality at 28 days in sepsis: a retrospective cohort study.

BACKGROUND Low serum cholesterol is known to be associated with poor prognosis in sepsis patients. On the other hand, there have been few studies on the association between high serum cholesterol, one of the major risk factors for cardiovascular adverse events, and prognosis of sepsis patients. We investigated the relationship between the serum total cholesterol concentration and outcome of sepsis patients. METHODS We conducted a multicenter retrospective cohort study at the emergency departments (EDs) of three urban tertiary teaching hospitals. Patients were divided into three groups according to the initial serum total cholesterol concentration: low cholesterol (cholesterol <120 mg/dL), normal cholesterol (cholesterol 120-200 mg/dL), and high cholesterol (cholesterol >200 mg/dL). Multivariable Cox proportional hazard regression model was used to identify the independent association between the serum total cholesterol concentrations and mortality at 28 days. RESULTS A total of 4,512 patients were included in the final analysis. The mortality at 28 days of the low, normal, and high cholesterol groups were 24.1%, 14.5%, and 20.5%, respectively (P<0.001). Both the low and high cholesterol groups had a higher risk of death than the normal cholesterol group (low cholesterol group [hazard ratio (HR), 1.46; 95% confidence interval (CIs), 1.25-1.71] and high cholesterol group (HR, 1.57; 95% CI, 1.14-2.16). CONCLUSIONS Both low and high serum total cholesterol concentrations were associated with higher mortality at 28 days in sepsis patients.
Monitoring Circulating Tumor DNA During Surgical Treatment in Patients with Gastrointestinal Stromal Tumors

The majority of patients diagnosed with advanced gastrointestinal stromal tumors (GISTs) are successfully treated with a combination of surgery and tyrosine kinase inhibitors (TKIs). However, it remains challenging to monitor treatment efficacy and identify relapse early. Here, we utilized a sequencing strategy based on molecular barcodes and developed a GIST-specific panel to monitor tumor-specific and TKI resistance mutations in cell-free DNA and applied the approach to patients undergoing surgical treatment. Thirty-two patients with GISTs were included, and 161 blood plasma samples were collected and analyzed at routine visits before and after surgery and at the beginning, during, and after surgery. Patients were included regardless of their risk category. Our GIST-specific sequencing approach allowed detection of tumor-specific mutations and TKI resistance mutations with mutant allele frequency < 0.1%. Circulating tumor DNA (ctDNA) was detected in at least one timepoint in nine of 32 patients, ranging from 0.04% to 93% in mutant allele frequency. High-risk patients were more often ctDNA positive than other risk groups (P < 0.05). Patients with detectable ctDNA also displayed higher tumor cell proliferation rates (P < 0.01) and larger tumor sizes (P < 0.01). All patients who were ctDNA positive during surgery became negative after surgery. Finally, in two patients who progressed on TKI treatment, we detected multiple resistance mutations. Our data show that ctDNA may become a clinically useful biomarker in monitoring treatment efficacy in patients with high-risk GISTs and can assist in treatment decision making.
A Case of Hypophysitis Following Immunization With the mRNA-1273 SARS-CoV-2 Vaccine

The emergence of a novel coronavirus and global pandemic raised the need for the rapid development of new vaccines to reduce the morbidity and mortality associated with Covid-19. Common side effects of these vaccines such as myalgia, arthralgia, nausea, fatigue, and injection site reaction are usually self-resolving. Recognition of other potential adverse effects of these novel vaccines is important due to their rapid and widespread distribution. We report a case of a 51-year-old man admitted to Parkland Memorial Hospital with headache, nausea, vomiting, malaise, and diffuse arthralgias 3 days after he received his second mRNA-1273 SARS-CoV-2 vaccination. He was found to have hyponatremia and a low serum cortisol level. Further workup revealed hypopituitarism with central hypothyroidism, hypogonadism, and a subnormal response to cosyntropin. Magnetic resonance imaging revealed a diffusely enlarged pituitary gland consistent with acute hypophysitis. The patient responded well to glucocorticoid and thyroid hormone supplementation and was discharged after 2 days in the hospital. This is the first reported case of hypopituitarism potentially associated with Covid-19 immunization.
In vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer’s disease pathology and cognitive decline

Description In vivo and autopsy evidence supports locus coeruleus MRI measures as proxy of initial TAU deposition and amyloid-related memory decline. Determining AD trajectories The locus coeruleus (LC) has been recognized as initial site of TAU aggregation in Alzheimer’s disease (AD). However, how LC pathology relates to disease progression and symptoms remains to be elucidated. Now, Jacobs et al. used MRI and PET longitudinal data in cognitively impaired and unimpaired individuals and postmortem data from two large cohorts of patients with AD and showed that the integrity of the LC is associated with the main pathological and cognitive features of preclinical AD, suggesting that monitoring LC using noninvasive imaging methods might help to predict cognitive trajectories and AD pathology later in life. Several autopsy studies recognize the locus coeruleus (LC) as the initial site of hyperphosphorylated TAU aggregation, and as the number of LC neurons harboring TAU increases, TAU pathology emerges throughout the cortex. By conjointly using dedicated MRI measures of LC integrity and TAU and amyloid PET imaging, we aimed to address the question whether in vivo LC measures relate to initial cortical patterns of Alzheimer’s disease (AD) fibrillar proteinopathies or cognitive dysfunction in 174 cognitively unimpaired and impaired older individuals with longitudinal cognitive measures. To guide our interpretations, we verified these associations in autopsy data from 1524 Religious Orders Study and Rush Memory and Aging Project and 2145 National Alzheimer’s Coordinating Center cases providing three different LC measures (pigmentation, tangle density, and neuronal density), Braak staging, β-amyloid, and longitudinal cognitive measures. Lower LC integrity was associated with elevated TAU deposition in the entorhinal cortex among unimpaired individuals consistent with postmortem correlations between LC tangle density and successive Braak staging. LC pigmentation ratings correlated with LC neuronal density but not with LC tangle density and were particularly worse at advanced Braak stages. In the context of elevated β-amyloid, lower LC integrity and greater cortical tangle density were associated with greater TAU burden beyond the medial temporal lobe and retrospective memory decline. These findings support neuropathologic data in which early LC TAU accumulation relates to disease progression and identify LC integrity as a promising indicator of initial AD-related processes and subtle changes in cognitive trajectories of preclinical AD.
Azulene-Modified Polysiloxanes as Gas Chromatographic Stationary Phases: Comparison of the Separatory Properties of Azulene and Naphthalene

ABSTRACT Azulene is an aromatic molecule with interesting properties, most notably a permanent dipole moment of 1.08D. This degree of polarity in the absence of heteroatoms is quite rare and offers potential for use in unique gas chromatographic stationary phases. Here, we report the first examples of azulene-derivatized stationary phases for gas chromatographic separations. Poly(dimethyl/azulenylmethyl) siloxane polymers containing 15 and 35% of an azulene derivative were synthesized, coated on capillary columns, and evaluated. To compare the effects of increased polarity vs. the effects of polarizability, isomeric naphthalene analogues were also prepared, coated, and evaluated. The coated phases displayed efficiencies up to 2700 plates/m. For both azulene and naphthalene columns, retention increased as substitution level increased. The more polarizable naphthalene columns tended to retain analytes more strongly. Columns were also evaluated for the separation of several different mixtures of isomers against a commercial HP-5 column. All azulene and naphthalene columns exhibited separations comparable to the commercial column. The solvation thermodynamic parameters phases were measured, showing an excellent linear relationship and no change in the mechanism of interaction over the temperature range measured.
Race, Genetic Ancestry, and Estimating Kidney Function in CKD.

BACKGROUND The inclusion of race in equations to estimate the glomerular filtration rate (GFR) has become controversial. Alternative equations that can be used to achieve similar accuracy without the use of race are needed. METHODS In a large national study involving adults with chronic kidney disease, we conducted cross-sectional analyses of baseline data from 1248 participants for whom data, including the following, had been collected: race as reported by the participant, genetic ancestry markers, and the serum creatinine, serum cystatin C, and 24-hour urinary creatinine levels. RESULTS Using current formulations of GFR estimating equations, we found that in participants who identified as Black, a model that omitted race resulted in more underestimation of the GFR (median difference between measured and estimated GFR, 3.99 ml per minute per 1.73 m2 of body-surface area; 95% confidence interval [CI], 2.17 to 5.62) and lower accuracy (percent of estimated GFR within 10% of measured GFR [P10], 31%; 95% CI, 24 to 39) than models that included race (median difference, 1.11 ml per minute per 1.73 m2; 95% CI, -0.29 to 2.54; P10, 42%; 95% CI, 34 to 50). The incorporation of genetic ancestry data instead of race resulted in similar estimates of the GFR (median difference, 1.33 ml per minute per 1.73 m2; 95% CI, -0.12 to 2.33; P10, 42%; 95% CI, 34 to 50). The inclusion of non-GFR determinants of the serum creatinine level (e.g., body-composition metrics and urinary excretion of creatinine) that differed according to race reported by the participants and genetic ancestry did not eliminate the misclassification introduced by removing race (or ancestry) from serum creatinine-based GFR estimating equations. In contrast, the incorporation of race or ancestry was not necessary to achieve similarly statistically unbiased (median difference, 0.33 ml per minute per 1.73 m2; 95% CI, -1.43 to 1.92) and accurate (P10, 41%; 95% CI, 34 to 49) estimates in Black participants when GFR was estimated with the use of cystatin C. CONCLUSIONS The use of the serum creatinine level to estimate the GFR without race (or genetic ancestry) introduced systematic misclassification that could not be eliminated even when numerous non-GFR determinants of the serum creatinine level were accounted for. The estimation of GFR with the use of cystatin C generated similar results while eliminating the negative consequences of the current race-based approaches. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).
Bluebirds Experience Impaired Hatching Success in Conventionally Sprayed Apple Orchard Habitats: A 31‐Year Study

We analyzed the reproductive success of eastern bluebirds (Sialia sialis) nesting in apple orchards and non‐orchard nest‐boxes in southern Ontario, Canada, from 1988 to 2018. Using data from 2397 nest‐boxes monitored at 20 orchard sites and 52 non‐orchard sites, we first modeled phenological parameters typically linked to climate change across both site types. We found that the first egg of each brood was laid significantly earlier in the season each year over our 31‐year study. Clutch initiation occurred 4 days earlier in the spring in 2018 compared to 1988. Average clutch size in the first or second brood did not change significantly during our 31‐year study; however, clutches were significantly smaller in orchards compared to non‐orchards (0.10 ± 0.03 fewer eggs between sites). Nests built in orchards were also at 6.1‐fold greater risk of parasitism and 2.1‐fold greater risk of depredation than nests in non‐orchards. After accounting for depredation and nest parasitism, hatching success was still significantly lower in orchards than in non‐orchards. Overall, hatching success was 4%–5% lower in orchards. The probability of successfully fledging did not differ significantly between site types. In 2012, a ban on use of the organophosphate insecticide azinphos‐methyl in orchards was enacted in Canada. We did not find a difference in hatching or fledging success in orchards after the ban. In our assessment of available data, we conclude that any pesticide effect on hatching success of eastern bluebirds in sprayed orchards is most likely the consequence of long‐term exposure to dichlorodiphenyltrichloroethane (DDT) compounds in orchard soils and bioaccumulation in eggs rather than pesticides in use since regulation of DDT in the 1970s. Environ Toxicol Chem 2021;40:3369–3378. © 2021 Her Majesty the Queen in Right of Canada. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Reproduced with the permission of the Minister of Environment and Climate Change Canada.
Does education matter for psychological recovery amidst the COVID-19 pandemic? Evidence from a panel survey in Hubei, China

ABSTRACT Objectives Little has been done to examine socioeconomic differences in the trajectory of psychological well-being during a disaster. This paper investigates educational differences in the changes in psychological well-being during the COVID-19 pandemic and explores the mechanisms of the differences. Methods The data were obtained from a unique two-wave panel survey conducted during the peak and waning phases of the pandemic in Hubei province, the epicenter of the pandemic in China. Results At the peak of the pandemic, individuals with different levels of education reported high and similar levels of psychological distress. As the pandemic subsided, the psychological well-being of people of all educational levels rebounded, but the recovery was greater and faster for those with tertiary education. Mediation analysis shows that neighborhood social support and evaluation of the performance of grassroots government partially explained the advantage of the more highly educated. Conclusion This study reveals how social differentiation is translated into health disparities when a disaster strikes. It may also inform public policy by identifying segments of the population at heightened risk of psychological distress during the COVID-19 pandemic.
Control of Salvinia molesta with imazamox and analysis of environmental indicators in microcosms

Abstract The aim of this study was to assess the efficacy of imazamox for control of S. molesta and to assess the effects of plant decomposition on environmental indicators after application of this herbicide in microcosm conditions. The following rates were used: 600, 700, 800 and 900 g ai ha−1 and spray volume 50 L ha−1. Control efficacy was determined as the percentage (from 0 to 100%) of visible injury symptoms in the plants, biochemical and chemical oxygen demand (BOD5 and COD), water quality variables, chlorophyll a and pheophytin a at 0, 7, 15, 30, 45 and 60 days after application (DAA) and fresh and dry biomass at 60 DAA. Imazamox was effective in controlling 94% of S. molesta with 900 g ai ha−1; it reduced 95% of fresh weight and 92% of dry weight of plant at 60 DAA, and reduced chlorophyll a of the plants for all rates. For BOD5, there was an increase for all rates at 15, 30 and 45 DAA with restoration of the parameters at 60 DAA, and for COD, there was an increase at 60 DAA with 700 and 900 g ai ha−1. For temperature, pH, dissolved oxygen and electrical conductivity, there was no significant effect after spraying. Imazamox was effective in controlling S. molesta with 900 g ai ha−1 without causing significant effects on the physical-chemical parameters of water quality.
Effects of light and water disturbance on the growth of Microcystis aeruginosa and the release of algal toxins

Eutrophication of water constitutes a serious threat to global water quality. Light intensity and water disturbance are important factors affecting the growth of algae and the release of algal toxins. In this study, algal growth indicators, algal enzyme systems, and algal toxin release in Microcystis aeruginosa under different light intensities and water disturbances were determined. The results showed that 2500 lx and 120 rpm were the optimal conditions for the growth of M. aeruginosa. The growth of algal cells was inhibited by high light intensity and high water disturbance. However, the optimal conditions for algal growth were not favorable conditions for the release of algal toxin. The highest concentration of microcystin‐LR (MC‐LR), observed at 4500 lx and 80 rpm, was 198.1 μg/L, whereas the highest single cell toxin production reached up to 10.49 × 10−9 μg/cell at 7000 lx and 120 rpm. Redundancy analysis results showed that the concentration of MC‐LR was positively correlated with algal cell density and antioxidant enzyme activities (superoxide dismutase, catalase, peroxidase, and malondialdehyde [MDA]) and negatively correlated with the total nitrogen and total phosphorus consumption rates and MDA. Single cell toxin production was negatively correlated with algal cell density and antioxidant enzyme activity but positively correlated with MDA content.
Diet and gut microbiota manipulation for the management of Crohn's disease and ulcerative colitis

The aetiology of inflammatory bowel disease (IBD) is multifactorial, with diet and gut microbiota playing an important role. Nonetheless, there are very few studies, particularly clinical research, which have explored the interaction between diet and gut microbiota. In the current review, we summarise the evidence from clinical trials exploring the interactions between the gut microbiota and diet in the management of IBD. Data from the effect of exclusive enteral nutrition (EEN) on the gut microbiota of children with active Crohn's disease (CD), receiving induction treatment, offer opportunities to understand the role of gut microbiota in underlying disease pathogenesis and develop novel dietary and pharmacological microbial therapeutics. In contrast, the evidence which links the effectiveness of food-based dietary therapies for IBD with mechanisms involving the gut microbiota is far less convincing. The microbial signals arising from these dietary therapies are inconsistent and vary compared to the effects of effective treatment with EEN in CD.
Virtual monoenergetic dual-energy CT reconstructions at 80 keV are optimal non-contrast CT technique for early stroke detection

Background Virtual monoenergetic (VM) dual-energy computed tomography (DE-CT) enables grey-to-white matter contrast-to-noise ratio optimization, potentially increasing ischaemic brain oedema visibility. The aim of this study was to compare the diagnostic accuracy of VM and standard DE-CT reconstructions for early stroke detection. Methods Consecutive patients with non-contrast DE-CT of the brain scanned within 12 h of stroke symptom onset were prospectively included in the study. Patients with other significant brain pathology were excluded. Two radiologists jointly evaluated standard and VM reconstructions (from 40 to 190 keV at increments of 10 keV) for early stroke signs on a four-point Likert scale: (a) stroke definitely present, (b) stroke probably present, (c) probably no stroke, and (d) definitely no stroke. Follow-up imaging and clinical data served as the standard of reference. Diagnostic accuracy was evaluated by receiver operating characteristic analysis. Results Stroke incidence among 184 patients was 76%. In 64 patients follow-up imaging served as the standard of reference: ischemic brain oedema detection was significantly more accurate on VM reconstructions at 80 keV compared with standard DE-CT reconstructions (area under the curve (AUC) = 0.821 vs. AUC = 0.672, p = 0.002). The difference was most prominent within the first 3 h after symptom onset (at 11%, AUC = 0.819 vs. AUC = 0.709, p = 0.17) and in patients with National Institutes of Health Stroke Scale above 16 (at 37.5%, AUC = 1 vs. AUC = 0.625, p = 0.14). Conclusion VM DE-CT reconstructions at 80 keV appear to be the optimal non-contrast CT technique for diagnosing early ischaemic stroke, particularly within the first 3 h after symptom onset and in severely ill patients.