Miracle-dz/UniFAR-FTUs huggingface dataset:
Terminal Arbors of Callosal Axons Undergo Plastic Changes in Early-Amputated Rats

Sensory information is processed in specific brain regions, and shared between the cerebral hemispheres by axons that cross the midline through the corpus callosum. However, sensory deprivation usually causes sensory losses and/or functional changes. This is the case of people who suffered limb amputation and show changes of body map organization within the somatosensory cortex (S1) of the deafferented cerebral hemisphere (contralateral to the amputated limb), as well as in the afferented hemisphere (ipsilateral to the amputated limb). Although several studies have approached these functional changes, the possible finer morphological alterations, such as those occurring in callosal axons, still remain unknown. The present work combined histochemistry, single-axon tracing and 3D microscopy to analyze the fine morphological changes that occur in callosal axons of the forepaw representation in early amputated rats. We showed that the forepaw representation in S1 was reduced in the deafferented hemisphere and expanded in the afferented side. Accordingly, after amputation, callosal axons originating from the deafferented cortex undergo an expansion of their terminal arbors with increased number of terminal boutons within the homotopic representation at the afferented cerebral hemisphere. Similar microscale structural changes may underpin the macroscale morphological and functional phenomena that characterize limb amputation in humans.
Strategic labelling approaches for RNA single-molecule spectroscopy

ABSTRACT Most single-molecule techniques observing RNA in vitro or in vivo require fluorescent labels that have to be connected to the RNA of interest. In recent years, a plethora of methods has been developed to achieve site-specific labelling, in many cases under near-native conditions. Here, we review chemical as well as enzymatic labelling methods that are compatible with single-molecule fluorescence spectroscopy or microscopy and show how these can be combined to offer a large variety of options to site-specifically place one or more labels in an RNA of interest. By either chemically forming a covalent bond or non-covalent hybridization, these techniques are prerequisites to perform state-of-the-art single-molecule experiments.
Genetic diversity and amino acid sequence polymorphism in Helicobacter pylori CagL hypervariable motif and its association with virulence markers and gastroduodenal diseases

Genetic variability in cagL gene especially within the Helicobacter pylori CagL hypervariable motif (CagLHM) may affect the development of gastric cancer. Therefore, this study was conducted to investigate the association of CagL diversity with clinical outcomes and with H pylori virulence markers. A total of 126 patients with different gastric diseases including non‐ulcer dyspepsia (NUD), peptic ulcer disease (PUD), gastric erosion (GE), and gastric cancer (GC) were enrolled. H pylori was cultured from gastric biopsies, and the isolates were screened for the presence of cagL, cagA, vacA, babA2, sabA, and cagPAI integrity by PCR. The amino acid polymorphisms of cagL were analyzed using DNA sequencing. We isolated 61 (48.4%) H pylori strains from 36 NUD, eight PUD, 12 GE, and five GC patients. Almost all isolates were cagL positive (97%), and their RGD, RHS, and SKIIVK motifs were highly conserved. Among 10 CagLHM variants identified, NEIGQ and NKIGQ were detected as the most prevalent sequences. Interestingly, a significant association was found between the presence of NKMGK and PUD (P = 0.002). Notably, the NEIGQ isolates with multiple C‐type EPIYA repeat that carried intact cagPAI correlated with disease risk for PUD, GE, and GC (P = 0.021). In conclusion, we identified novel variants of H pylori CagLHM sequences in Iranian population such as NKMGK, which was associated with disease risk for PUD. Further studies using a large number of strains are required to better clarify the function of certain CagLHM motifs in gastric carcinogenesis and disease outcome.
Telomere length, arsenic exposure and risk of basal cell carcinoma of skin

Telomere length per se a heritable trait has been reported to be associated with different diseases including cancers. In this study based on arsenic exposed 528 cases with basal cell carcinoma of skin (BCC) and 533 healthy controls, we observed a statistically significant association between decreased telomere length and increased BCC risk (OR = 5.92, 95% CI = 3.92-9.01, P<0.0001). We also observed that higher arsenic exposure (>1.32 µg/L) was statistically significantly associated with decreased telomere length (β = −0.026, 95% CI = − 0.05-0.003, P = 0.02). The interaction between arsenic exposure and telomere length on BCC risk was statistically significant (P = 0.02). Within each tertile based on arsenic exposure, the individuals with shorter telomeres were at an increased risk of BCC, with highest risk being in the highest exposed group (OR = 16.13, 95% CI = 6.71-40.00, P<0.0001); followed by those in medium exposure group (OR = 5.05, 95% CI = 2.29-10.20, P <0.0001), and low exposure group (OR = 3.44, 95% CI = 1.81-6.54, P = 0.0002). The combined effect of highest arsenic exposure and shortest telomeres on the risk of BCC (OR = 10.56, 95% CI = 5.14-21.70) showed a statistically significant departure from additivity (interaction constant ratio 6.56, P = 0.03). Our results show that in the presence of arsenic exposure, decreased telomere length predisposes individuals to increased risk of BCC, with the effect being synergistic in individuals with highest arsenic exposure and shortest telomeres.
Impact of Pulmonary Exposure to Cerium Oxide Nanoparticles on Experimental Acute Kidney Injury.

BACKGROUND/AIMS Cerium oxide nanoparticles (CeO₂ NPs) are released from diesel engines that use cerium compounds as a catalytic agent to decrease the diesel exhaust particles, leading to human exposure by inhalation to CeO₂ NPs. We have recently demonstrated that pulmonary exposure to CeO₂ NPs induces lung inflammation, thrombosis, and oxidative stress in various organs including kidneys. It is well known that particulate air pollution effects are greater in patients with renal diseases. The aim of this study is to investigate the effects of pulmonary exposure to CeO₂ NPs in a rat model of acute kidney injury (AKI). METHODS AKI was induced in rats by a single intraperitoneal injection of cisplatin (CP, 6 mg/kg). Six days later, the rats were intratracheally (i.t.) instilled with either CeO₂ NPs (1 mg/kg) or saline (control), and various renal and pulmonary endpoints were assessed 24 h afterward using histological, colorimetric assay, enzyme-linked immunosorbent assay and Comet assay techniques. RESULTS CP alone decreased body weight, and increased water intake, urine volume and relative kidney weight. CP also increased the plasma concentrations urea and creatinine, and decreased creatinine clearance. In the kidneys, CP significantly increased renal injury molecule-1, interleukin-6 (IL-6), tumor necrosis factor α (TNFα) and glutathione concentrations, and caused renal tubular necrosis, and DNA injury assessed by Comet assay. All these actions were significantly aggravated in rats given both CP and CeO₂ NPs. Histopathological changes in lungs of CeO₂ NPs-treated rats included marked interstitial cell infiltration and congestion. These were aggravated by the combination of CP + CeO₂ NPs. Moreover, this combination exacerbated the increase in the concentrations of TNFα and IL-6, and the decrease in the activity of pulmonary catalase and total nitric oxide concentration, and lung DNA damage. CONCLUSION We conclude that the presence of CeO₂ NPs in the lung exacerbated the renal and lung effects of CP-induced AKI.
Evaluation of Indian Prediction Models for Lung Function Parameters: A Statistical Approach

Background: Interpretation of lung function test parameters is usually based on comparisons of data with reference (predicted) values based on healthy subjects. Predicted values are obtained from studies of “normal” or “healthy” subjects with similar anthropometric and ethnic characteristics. Regression models are generally used to obtain the reference values from measurements observed in a representative sample of healthy subjects. Objectives: The study aims to carry out a statistical evaluation of the Indian prediction models of lung function parameters and critically evaluate the reference values for the same in an Indian context. Methods: The screening and inclusion of the articles for the study was done using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Evaluation of the prediction models has been done with respect to modeling approach, regression diagnostics and methodology protocol. The suitability of the models has also been evaluated using a checklist comprising of 8 criteria developed using the American Thoracic Society (ATS) guidelines. Results: Using the PRISMA guidelines 32 articles with a total sample size of 25,289 subjects were included in the final synthesis. Multiple linear regression models were used in 27 articles, with one additionally using weighted least squares technique and 4 using step-wise regression method. Regression diagnostics as per the ATS guidelines were performed and reported by 22 articles. The prediction models were traditionally developed using ordinary least squares method (OLS) without examining the homoskedasticity of residuals. The quality assessment using the checklist developed revealed that only 5 articles satisfied more than 7 out of 8 criteria, and a further 8 articles satisfied less than 3 criteria of suitability of prediction models. Conclusions: Indian prediction models for lung function models are traditionally based on linear regression models, however with more advancement in computational power for sophisticated statistical techniques, more robust prediction models are required in the Indian context.
Brassinosteroid signaling in plant development and adaptation to stress

ABSTRACT Brassinosteroids (BRs) are steroid hormones that are essential for plant growth and development. These hormones control the division, elongation and differentiation of various cell types throughout the entire plant life cycle. Our current understanding of the BR signaling pathway has mostly been obtained from studies using Arabidopsis thaliana as a model. In this context, the membrane steroid receptor BRI1 (BRASSINOSTEROID INSENSITIVE 1) binds directly to the BR ligand, triggering a signal cascade in the cytoplasm that leads to the transcription of BR-responsive genes that drive cellular growth. However, recent studies of the primary root have revealed distinct BR signaling pathways in different cell types and have highlighted cell-specific roles for BR signaling in controlling adaptation to stress. In this Review, we summarize our current knowledge of the spatiotemporal control of BR action in plant growth and development, focusing on BR functions in primary root development and growth, in stem cell self-renewal and death, and in plant adaption to environmental stress. Summary: This Review summarizes current knowledge of the spatiotemporal control of brassinosteroid function in plants, focusing on primary root development and growth, stem cell self-renewal and death, and adaptation to environmental stress.
Periventricular White Matter Abnormalities on Diffusion Tensor Imaging of Postural Instability Gait Disorder Parkinsonism

BACKGROUND AND PURPOSE: Postural instability gait disorder is a motor subtype of Parkinson disease associated with predominant gait dysfunction. We investigated the periventricular white matter comprising longitudinal, thalamic, and callosal fibers using diffusion tensor MR Imaging and examined clinical correlates in a cohort of patients with Parkinson disease and postural instability gait disorder and healthy controls. MATERIALS AND METHODS: All subjects underwent the Tinetti Gait and Balance Assessment and brain MR imaging. The DTI indices (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) from ROIs dropped over the superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculus, anterior thalamic radiation, anterior and posterior limbs of the internal capsule, and the genu and body of corpus callosum were evaluated. RESULTS: Our findings showed that the superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, anterior thalamic radiation, genu of the corpus callosum, and body of the corpus callosum are more affected in postural instability gait disorder than in those with Parkinson disease or healthy controls, with more group differences among the longitudinal fibers. Only the callosal fibers differentiated the postural instability gait disorder and Parkinson disease groups. DTI measures in the superior longitudinal fasciculus, frontostriatal fibers (anterior thalamic radiation, anterior limb of the internal capsule), and genu of the corpus callosum fibers correlated with clinical gait severity. CONCLUSIONS: Findings from this case-control cohort lend further evidence to the role of extranigral pathology and, specifically, the periventricular fibers in the pathophysiology of postural instability gait disorder.
The Deletion of TRPC6 Channels Perturbs Iron and Zinc Homeostasis and Pregnancy Outcome in Mice.

BACKGROUND/AIMS Transient receptor potential canonical 6 (TRPC6) protein is a nonselective cation channel permitting the uptake of essential elements such as iron (Fe) and zinc (Zn). TRPC6 is found throughout the body with high expression levels in the placenta. However, its role in this organ is still to be determined. To further advance our understanding of the physiological relevance of TRPC6, we have studied the placental histology, pregnancy outcome and the Fe and Zn status of organs (placenta, brain, kidney, liver and lung) collected from TRPC6 deficient (TRPC6-/-) mice and sex and age-matched C57Bl6/J and B6129SF2/J mice. METHODS Metal content was quantified by inductively coupled plasma-atomic emission spectrometry (ICP-AES). Quantitative reverse transcriptase PCR (qRT-PCR) and Western Blottings (WB) were performed to analyze the expression of placental markers and TRPC6. RESULTS Our data show that TRPC6-/- mice displayed reduced litter sizes, structural changes of the placenta, along with altered mRNA levels of CD31 and Gcm1, two markers of placental development. Furthermore, immunoblots revealed elevated amounts of TRPC6 proteins in placentas from women diagnosed with preeclampsia, a common gestational disease. When compared to C57Bl6/J and B6129SF2/J, TRPC6-/- mice had elevated Zn levels in placenta, liver and kidney during embryonic development and postnatally, but not at adulthood. High amounts of Fe were found in the adult brain and liver of TRPC6-/- mice. The lung was however not affected by the deletion of TRPC6, indicating that this mouse strain developed organ and age-dependent perturbations in their Zn and Fe status. CONCLUSION This work indicates that TRPC6 exerts critical pathophysiological functions in placenta, and provides further evidence for a role of this channel in the homeostasis of cations like Zn and Fe.
Persistent Wheeze in Infants: A Guide for General Pediatricians.

Infants with persistent wheeze is a common diagnostic challenge for the general pediatrician because of the broad differential diagnoses. The initial diagnostic approach should include a comprehensive history, physical examination, and chest radiography. Additional testing may be warranted. Involvement of a pediatric pulmonary subspecialist may also be indicated. [Pediatr Ann. 2019;48(3):e110-e114. ].
New York City Panel on Climate Change 2019 Report Chapter 6: Community‐Based Assessments of Adaptation and Equity

Sheila Foster,1 Robin Leichenko,2 Khai Hoan Nguyen,2 Reginald Blake,3 Howard Kunreuther,4 Malgosia Madajewicz,5 Elisaveta P. Petkova,5 Rae Zimmerman,6 Cecil Corbin-Mark,7 Elizabeth Yeampierre,8 Angela Tovar,9 Cynthia Herrera,5,7 and Daron Ravenborg10 1Georgetown University, Washington, DC. 2Rutgers University, New Brunswick, New Jersey. 3New York City College of Technology, New York, New York. 4University of Pennsylvania, Philadelphia, Pennsylvania. 5Columbia University, New York, New York. 6New York University, New York, New York. 7WE ACT, New York, New York. 8UPROSE, New York, New York. 9THE POINT, New York, New York. 10Fordham School of Law, New York, New York
Tandem Fluorescent Protein Timers for Noninvasive Relative Protein Lifetime Measurement in Plants

Tandem fluorescent protein timers enable non-invasive analysis of protein turnover in intact plant cells, allowing tests of how different genetic backgrounds and treatments affect protein stability. Targeted protein degradation is an important and pervasive regulatory mechanism in plants, required for perception and response to the environment as well as developmental signaling. Despite the significance of this process, relatively few studies have assessed plant protein turnover in a quantitative fashion. Tandem fluorescent protein timers (tFTs) offer a powerful approach for the assessment of in vivo protein turnover in distinct subcellular compartments of single or multiple cells. A tFT is a fusion of two different fluorescent proteins with distinct fluorophore maturation kinetics, which enable protein age to be estimated from the ratio of fluorescence intensities of the two fluorescent proteins. Here, we used short-lived auxin signaling proteins and model N-end rule (N-recognin) pathway reporters to demonstrate the utility of tFTs for studying protein turnover in living plant cells of Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana. We present transient expression of tFTs as an efficient screen for relative protein lifetime, useful for testing the effects of mutations and different genetic backgrounds on protein stability. This work demonstrates the potential for using stably expressed tFTs to study native protein dynamics with high temporal resolution in response to exogenous or endogenous stimuli.
Effect of Catheter Ablation vs Medical Therapy on Quality of Life Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial

Importance Catheter ablation is more effective than drug therapy in restoring sinus rhythm in patients with atrial fibrillation (AF), but its incremental effect on long-term quality of life (QOL) is uncertain. Objective To determine whether catheter ablation is more beneficial than conventional drug therapy for improving QOL in patients with AF. Design, Setting, and Participants An open-label randomized clinical trial of catheter ablation vs drug therapy in 2204 symptomatic patients with AF older than 65 years or 65 years or younger with at least 1 risk factor for stroke. Patients were enrolled from November 2009 to April 2016 from 126 centers in 10 countries. Follow-up ended in December 2017. Interventions Pulmonary vein isolation, with additional ablation procedures at the discretion of the investigators, for the catheter ablation group (n = 1108) and standard rhythm and/or rate-control drugs selected and managed by investigators for the drug therapy group (n = 1096). Main Outcomes and Measures Prespecified co-primary QOL end points at 12 months, including the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary score (range, 0-100; 0 indicates complete disability and 100 indicates no disability; patient-level clinically important difference, ≥5 points) and the Mayo AF-Specific Symptom Inventory (MAFSI) frequency score (range, 0-40; 0 indicates no symptoms and 40 indicates the most severe symptoms; patient-level clinically important difference, ⩽−1.6 points) and severity score (range, 0-30; 0 indicates no symptoms and 30 indicates the most severe symptoms; patient-level clinically important difference, ⩽−1.3 points). Results Among 2204 randomized patients (median age, 68 years; 1385 patients [63%] were men, 946 [43%] had paroxysmal AF, and 1256 [57%] had persistent AF), the median follow-up was 48.5 months, and 1968 (89%) completed the trial. The mean AFEQT summary score was more favorable in the catheter ablation group than the drug therapy group at 12 months (86.4 points vs 80.9 points) (adjusted difference, 5.3 points [95% CI, 3.7-6.9]; P < .001). The mean MAFSI frequency score was more favorable for the catheter ablation group than the drug therapy group at 12 months (6.4 points vs 8.1 points) (adjusted difference, −1.7 points [95% CI, −2.3 to −1.2]; P < .001) and the mean MAFSI severity score was more favorable for the catheter ablation group than the drug therapy group at 12 months (5.0 points vs 6.5 points) (adjusted difference, −1.5 points [95% CI, −2.0 to −1.1]; P < .001). Conclusions and Relevance Among patients with symptomatic atrial fibrillation, catheter ablation, compared with medical therapy, led to clinically important and significant improvements in quality of life at 12 months. These findings can help guide decisions regarding management of atrial fibrillation. Trial Registration ClinicalTrials.gov Identifier: NCT00911508
Note: High interest in doxycycline for sexually transmitted infection post-exposure prophylaxis (doxycycline-PEP) in a multi-city survey of men who have sex with men (MSM) using a social-networking app.

Current strategies to prevent sexually-transmitted infections (STI) are not controlling the epidemic. Doxycycline STI post-exposure prophylaxis' efficacy (doxycycline-PEP) shows promise in pilot studies, but wider acceptability is unknown. A majority (84%) of diverse individuals using a gay social-networking app were interested in doxycycline-PEP. Doxycycline-PEP should be examined in larger trials.
The Effect of an Infant Formula Supplemented with AA and DHA on Fatty Acid Levels of Infants with Different FADS Genotypes: The COGNIS Study

Polymorphisms in the fatty acid desaturase (FADS) genes influence the arachidonic (AA) and docosahexaenoic (DHA) acid concentrations (crucial in early life). Infants with specific genotypes may require different amounts of these fatty acids (FAs) to maintain an adequate status. The aim of this study was to determine the effect of an infant formula supplemented with AA and DHA on FAs of infants with different FADS genotypes. In total, 176 infants from the COGNIS study were randomly allocated to the Standard Formula (SF; n = 61) or the Experimental Formula (EF; n = 70) group, the latter supplemented with AA and DHA. Breastfed infants were added as a reference group (BF; n = 45). FAs and FADS polymorphisms were analyzed from cheek cells collected at 3 months of age. FADS minor allele carriership in formula fed infants, especially those supplemented, was associated with a declined desaturase activity and lower AA and DHA levels. Breastfed infants were not affected, possibly to the high content of AA and DHA in breast milk. The supplementation increased AA and DHA levels, but mostly in major allele carriers. In conclusion, infant FADS genotype could contribute to narrow the gap of AA and DHA concentrations between breastfed and formula fed infants.