Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigation of the effect of clinically relevant interferents on glucose monitoring using near‐infrared spectroscopy

Near infrared spectroscopy (NIR) is a promising technique for continuous blood glucose monitoring for diabetic patients. Four interferents, at physiological concentrations, were introduced to study how the glucose predictions varied with a standard multivariate calibration model. Lactate and ethanol were found to interfere strongly with the glucose predictions unless they were included in the calibration models. Lactate was mistaken for glucose and gave erroneously high glucose predictions, with a dose response of 0.46 mM/mM. The presence of ethanol resulted in too low glucose predictions, with a dose response of −0.43 mM/mM. Acetaminophen, a known interferent in the glucose monitoring devices used for diabetes management today, was not found to be an interferent in NIR spectroscopy, nor was caffeine. Thus, interferents that may appear in high concentrations, such as ethanol and lactate, must be included in the calibration or model building of future NIR‐based glucose measurement devices for diabetes monitoring.
Hydrothermal Synthesis and Thermoelectric Transport Properties of Uniform Single-Crystalline Pearl-Necklace-Shaped PbTe Nanowires

Uniform single-crystalline pearl-necklace-shaped PbTe nanowires with an average diameter of about 30 nm, smaller than its average excitonic Bohr radius of 46 nm, were successfully synthesized by a hydrothermal process using tellurium nanowires as templates and Pb(NO3)2 as a precursor at a molar ratio of 1:1. It is shown that the reaction temperature, duration, and concentration of Pb(NO3)2 play important roles in the formation of the PbTe nanowires. The growth process of the pearl-necklace-shaped PbTe nanowires can be reasonably explained by an oriented attachment mechanism. Thermoelectric transport measurement indicates that the film composed of the obtained PbTe nanowires has a Seebeck coefficient of about 307 μV/K, up to about 16% higher than that of the state-of-the-art bulk PbTe at room temperature. The synthetic route can be applied to obtain other low-dimensional semiconducting telluride nanostructures and optimization of the thermoelectric properties through nanowire alignment and doping may lead .
Motor patterns in the proximal and distal mouse colon which underlie formation and propulsion of feces

In herbivores, the proximal and distal colonic regions feature distinct motor patterns underlying formation and propulsion of fecal pellets, respectively. Omnivores, such as mice and humans, lack a similar clear anatomical transition between colonic regions. We investigated whether distinct processes form and propel content along the large intestine of a mouse (an omnivore).
Influence of the mode of heating on cerebral blood flow, non‐invasive intracranial pressure and thermal tolerance in humans

The human brain is particularly vulnerable to heat stress; this manifests as impaired cognition, orthostatic tolerance, work capacity and eventually, brain death. The brain's limitation in the heat is often ascribed to inadequate cerebral blood flow (CBF), but elevated intracranial pressure is commonly observed in mammalian models of heat stroke and can on its own cause functional impairment. The CBF response to incremental heat strain was dependent on the mode of heating, decreasing by 30% when exposed passively to hot, humid air (sauna), while remaining unchanged or increasing with passive hot‐water immersion (spa) and exercising in a hot environment. Non‐invasive intracranial pressure estimates (nICP) were increased universally by 18% at volitional thermal tolerance across all modes of heat stress, and therefore may play a contributing role in eliciting thermal tolerance. The sauna, more so than the spa or exercise, poses a greater challenge to the brain under mild to severe heating due to lower blood flow but similarly increased nICP.
Transcatheter aortic valve replacement after valve‐sparing aortic root surgery

The use of transcatheter aortic valves for aortic regurgitation presents unique challenges. Although studies describe their successful off‐label use, there is a paucity of literature on transcatheter aortic valve replacement after valve‐sparing aortic root surgery. We present a patient with severe aortic regurgitation following valve‐sparing aortic root replacement that was treated with an oversized transcatheter aortic valve.
Concomitant use of dexamethasone and tetracyclines: a potential therapeutic option for the management of severe COVID-19 infection?

ABSTRACT Introduction: The global coronavirus disease-2019 (COVID-19) pandemic has posed a critical challenge to the research community as well as to the healthcare systems. Severe COVID-19 patients are at a higher risk of developing serious complications and mortality. There is a dire need for safe and effective pharmacotherapy for addressing unmet needs of these patients. Concomitant use of dexamethasone and tetracyclines, by virtue of their immunomodulatory and other relevant pharmacological properties, offers a potential strategy for synergy aimed at improving clinical outcomes. Areas covered: Here we review the potential benefits of combining dexamethasone and tetracyclines (minocycline or doxycycline) for the management of severe COVID-19 patients. We have critically examined the evidence obtained from in silico, experimental, and clinical research. We have also discussed the plausible mechanisms, advantages, and drawbacks of this proposed combination therapy for managing severe COVID-19. Expert opinion: The concomitant use of dexamethasone and one of the tetracyclines among severe COVID-19 patients offers several advantages in terms of additive immunomodulatory effects, cost-effectiveness, wide-availability, and well-known pharmacological properties including adverse-effect profile and contraindications. There is an urgent need to facilitate pilot studies followed by well-designed and adequately-powered multicentric clinical trials to generate conclusive evidence related to utility of this approach.
Coronatine contributes to Pseudomonas cannabina pv. alisalensis virulence by overcoming both stomatal and apoplastic defenses in dicot and monocot plants.

Pseudomonas cannabina pv. alisalensis (Pcal) is a causative agent of bacterial blight of crucifer including cabbage, radish, and broccoli. Importantly, Pcal can infect not only a wide range of Brassicaceae, but also green manure crops such as oat. However, Pcal virulence mechanisms have not been investigated and are not fully understood. We focused on coronatine (COR) function, which is one of the well-known P. syringae pv. tomato DC3000 virulence factors, in Pcal infection processes on both dicot and monocot plants. Cabbage and oat plants dip-inoculated with a Pcal KB211 COR mutant (ΔcmaA) exhibited reduced virulence compared to Pcal WT. Moreover, ΔcmaA failed to reopen stomata on both cabbage and oat, suggesting that COR facilitates Pcal entry through stomata into both plants. Furthermore, cabbage and oat plants syringe-infiltrated with ΔcmaA also showed reduced virulence, suggesting that COR is involved in overcoming not only stomatal-based defense, but also apoplastic defense. Indeed, defense related genes, including PR1 and PR2, were highly expressed in plants inoculated with ΔcmaA compared to Pcal WT, indicating that COR suppresses defense-related genes of both cabbage and oat. Additionally, SA accumulation increases after ΔcmaA inoculation compared to Pcal WT. Taken together, COR contributes to cause disease by suppressing stomatal-based defense and apoplastic defense in both dicot and monocot plants. Here, we investigated COR functions in the interaction of Pcal and different host plants (dicot and monocot plants) using genetically and biochemically defined COR deletion mutants.
Revisiting the genome-wide significance threshold for common variant GWAS

Abstract Over the last decade, GWAS meta-analyses have used a strict P-value threshold of 5 × 10−8 to classify associations as significant. Here, we use our current understanding of frequently studied traits including lipid levels, height, and BMI to revisit this genome-wide significance threshold. We compare the performance of studies using the P = 5 × 10−8 threshold in terms of true and false positive rate to other multiple testing strategies: (1) less stringent P-value thresholds, (2) controlling the FDR with the Benjamini–Hochberg and Benjamini–Yekutieli procedure, and (3) controlling the Bayesian FDR with posterior probabilities. We applied these procedures to re-analyze results from the Global Lipids and GIANT GWAS meta-analysis consortia and supported them with extensive simulation that mimics the empirical data. We observe in simulated studies with sample sizes ∼20,000 and >120,000 that relaxing the P-value threshold to 5 × 10−7 increased discovery at the cost of 18% and 8% of additional loci being false positive results, respectively. FDR and Bayesian FDR are well controlled for both sample sizes with a few exceptions that disappear under a less stringent definition of true positives and the two approaches yield similar results. Our work quantifies the value of using a relaxed P-value threshold in large studies to increase their true positive discovery but also show the excess false positive rates due to such actions in modest-sized studies. These results may guide investigators considering different thresholds in replication studies and downstream work such as gene-set enrichment or pathway analysis. Finally, we demonstrate the viability of FDR-controlling procedures in GWAS.
Polymorphic variants INSIG2 rs6726538, HLA ‐ DRB1 rs9272143, and GCNT1P5 rs7780883 contribute to the susceptibility of cervical cancer in the Bangladeshi women

Cervical cancer is a gynecological health problem, affecting nearly 500,000 women each year worldwide. Genome‐wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical carcinoma risk. We have carried out this case‐control study to investigate the association of INSIG2 rs6726538 (A; T), HLA‐DRB1 rs9272143 (T; C), and GCNT1P5 rs7780883 (G; A) with cervical cancer.
Regional Disparities in Adherence to Guidelines for the Treatment of Chronic Heart Failure

Objective The incidence of chronic heart failure (CHF) is likely to keep increasing in Japan as the population ages, placing increased burdens on medical facilities, particularly on the limited numbers of rural hospitals. We explored the appropriateness of CHF treatment in rural areas in Japan. Methods We compared rates of adherence to therapeutic guidelines for CHF between residents with a left ventricular ejection fraction <35% living in urban areas (n = 207) and those in rural areas (n = 180). Treatments included pharmacological [beta-blockers, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blocker (ARB), mineralocorticoid receptor antagonist (MRA) and anticoagulants for atrial fibrillation] and non-pharmacological [implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy (CRT), cardiac rehabilitation and HF education] approaches. Patients This study included 387 patients with CHF, prior myocardial infarction or cardiomyopathy, and a left ventricular ejection fraction (LVEF) <35% as determined by echocardiography. Results The respective rates of treatments administered in urban and rural areas were as follows: beta-blockers, 91.3% vs. 61.7% (p<0.05); ACEi/ARB, 86.5% vs. 68.3% (p<0.05); MRA, 74.4% vs. 59.4% (p<0.01); anticoagulants, 100% vs. 86.5%, (p<0.05); ICD/CRT, 45.4% vs. 5.0% (p<0.05); cardiac rehabilitation, 32.4% vs. 13.3% (p<0.05) and HF education, 33.3% vs. 32.8% (p=0.75). Conclusion Regional disparities in treatment for CHF persist, even in Japan. Improvements in the use of guideline-directed treatment in rural areas might improve the outcomes for CHF patients.
Cellular and molecular mechanisms of Dementia: Decoding the causal link of Diabetes Mellitus in Alzheimer's disease.

Dementia and diabetes are the two major disorders that are linked at both biochemical and molecular levels which is due to the existing similarities between pancreatic beta-cells and neuronal cells at the transcription and translational levels. Both diseases have similar causative genes or factors and dementia is one of the advanced complications in about 50-52% of patients with type 2 diabetes mellitus (T2DM). Further, patients with T2DM are at a higher risk of neuronal degeneration and Alzheimer's disease (AD). Dementia, which is most common in AD, is associated with diminished insulin receptors by nearly 80%. The impairment in insulin signaling thus leads to the development of dementia and AD. Biochemical changes in 'tau' protein and amyloid-beta proteins, make them critical players in the formation of plaques in patients with dementia and AD. Here, we decode various cellular and molecular mechanisms associated with the development of dementia in patients with diabetes and AD.
Age-dependent changes in hormonal stress reactivity following repeated restraint stress throughout adolescence in male rats

Abstract Stress-related psychological dysfunctions show a marked increase during adolescence, yet the mechanisms that mediate these vulnerabilities are unknown. Notably, however, adolescence is associated with changes in hormonal stress reactivity mediated by the hypothalamic-pituitary-adrenal (HPA) axis, which might contribute to these dysfunctions. Specifically, pre-adolescent animals display prolonged stress-induced HPA responses compared to adults. Previous experience with stressors further modify these changes in stress reactivity, such that repeated exposure to the same stressor results in an augmented HPA response prior to adolescence, but a habituated response in adulthood. It is unclear when during adolescence the habituated, adult-like response develops to a repeated stressor. Using male rats at various ages that span adolescence (30–70 days of age), we show that by mid-adolescence (i.e. 42 days of age), animals show neither a facilitated nor a habituated HPA hormonal response following four days of repeated restraint stress (4RS) compared to a single restraint session (1RS). We also show that the habituated HPA response to 4RS develops between late-adolescence and young adulthood (i.e. between 56 and 70 days of age, respectively). Further, we find age- and experience-dependent changes in progesterone and testosterone secretion, indicating that the interaction between development and experience affects stress-induced hormonal responses outside of canonical HPA-related hormones. Despite these hormonal differences mediated by age and experience, repeated restraint stress resulted in decreased fecal boli production at all four ages, suggesting dissociation between hormonal and autonomic reactivity during adolescence. These data indicate that HPA plasticity is significantly affected by adolescence and that a habituated hormonal response to homotypic stress does not occur until young adulthood. A greater appreciation of these changes in stress reactivity will contribute to our understanding of the psychological vulnerabilities often associated with stressful adolescence.
Magnetic Resonance Iron Imaging in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) results in progressive impairment of upper and lower motor neurons. Increasing evidence from both in vivo and ex vivo studies suggest that iron accumulation in the motor cortex is a neuropathological hallmark in ALS. An in vivo neuroimaging marker of iron dysregulation in ALS would be useful in disease diagnosis and prognosis. Magnetic resonance imaging (MRI), with its unique capability to generate a variety of soft tissue contrasts, provides opportunities to image iron distribution in the human brain with millimeter to sub‐millimeter anatomical resolution. Conventionally, MRI T1‐weighted, T2‐weighted, and T2*‐weighted images have been used to investigate iron dysregulation in the brain in vivo. Susceptibility weighted imaging has enhanced contrast for para‐magnetic materials that provides superior sensitivity to iron in vivo. Recently, the development of quantitative susceptibility mapping (QSM) has realized the possibility of using quantitative assessments of magnetic susceptibility measures in brain tissues as a surrogate measurement of in vivo brain iron. In this review, we provide an overview of MRI techniques that have been used to investigate iron dysregulation in ALS in vivo. The potential uses, strengths, and limitations of these techniques in clinical trials, disease diagnosis, and prognosis are presented and discussed. We recommend further longitudinal studies with appropriate cohort characterization to validate the efficacy of these techniques. We conclude that quantitative iron assessment using recent advances in MRI including QSM holds great potential to be a sensitive diagnostic and prognostic marker in ALS. The use of multimodal neuroimaging markers in combination with iron imaging may also offer improved sensitivity in ALS diagnosis and prognosis that could make a major contribution to clinical care and treatment trials.
Workshop report. Circadian rhythm sleep–wake disorders: gaps and opportunities

Abstract This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep–wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.
Common Medications and Intracerebral Hemorrhage: The ARIC Study

Background Antiplatelets, anticoagulants, and statins are commonly prescribed for various indications. The associations between these medications and the risk of intracerebral hemorrhage (ICH) and cerebral microbleeds (CMBs) are unclear. Methods and Results We performed a retrospective study of the ARIC (Atherosclerosis Risk in Communities) study cohort, recruited from 4 US communities in 1987 to 1989 with follow‐up. In 2011 to 2013, a subset (N=1942) underwent brain magnetic resonance imaging with CMB evaluation. Time‐varying and any antiplatelet, anticoagulant, or statin use was evaluated at subsequent study visits in participants not on each medication at baseline. To determine the hazard of ICH and odds of CMB by medication use, logistic and Cox proportional hazard models were built, respectively, adjusting for the propensity to take the medication, concomitant use of other medications, and cognitive, genetic, and radiographic data. Of 15 719 individuals during up to 20 years of follow‐up, 130 participants experienced an ICH. The adjusted hazard of ICH was significantly lower among participants taking an antiplatelet at the most recent study visit before ICH versus nonusers (hazard ratio [HR], 0.53; 95% CI, 0.30–0.92). Statin users had a significantly lower hazard of an ICH compared with nonusers (adjusted HR, 0.13; 95% CI, 0.05–0.34). There was no association of CMB and antiplatelet, anticoagulant, or statin use in adjusted models. Conclusions In this US community‐based study, antiplatelet and statin use were associated with lower ICH hazard, whereas no association was noted between CMBs and antiplatelets, anticoagulants, and statins. Further study is needed to understand the differential roles of these medications in cerebral microhemorrhages and macrohemorrhages.
Human induced pluripotent stem cells and CRISPR/Cas‐mediated targeted genome editing: Platforms to tackle sensorineural hearing loss

Hearing loss (HL) is a major global health problem of pandemic proportions. The most common type of HL is sensorineural hearing loss (SNHL) which typically occurs when cells within the inner ear are damaged. Human induced pluripotent stem cells (hiPSCs) can be generated from any individual including those who suffer from different types of HL. The development of new differentiation protocols to obtain cells of the inner ear including hair cells (HCs) and spiral ganglion neurons (SGNs) promises to expedite cell‐based therapy and screening of potential pharmacologic and genetic therapies using human models. Considering age‐related, acoustic, ototoxic, and genetic insults which are the most frequent causes of irreversible damage of HCs and SGNs, new methods of genome editing (GE), especially the CRISPR/Cas9 technology, could bring additional opportunities to understand the pathogenesis of human SNHL and identify novel therapies. However, important challenges associated with both hiPSCs and GE need to be overcome before scientific discoveries are correctly translated to effective and patient‐safe applications. The purpose of the present review is (a) to summarize the findings from published reports utilizing hiPSCs for studies of SNHL, hence complementing recent reviews focused on animal studies, and (b) to outline promising future directions for deciphering SNHL using disruptive molecular and genomic technologies.