Miracle-dz/UniFAR-FTUs huggingface dataset:
Intraoperative Confocal Laser Endomicroscopy Ex Vivo Examination of Tissue Microstructure During Fluorescence-Guided Brain Tumor Surgery

Background Noninvasive intraoperative optical biopsy that provides real-time imaging of histoarchitectural (cell resolution) features of brain tumors, especially at the margin of invasive tumors, would be of great value. To assess clinical-grade confocal laser endomicroscopy (CLE) and to prepare for its use intraoperatively in vivo, we performed an assessment of CLE ex vivo imaging in brain lesions. Methods Tissue samples from patients who underwent intracranial surgeries with fluorescein sodium (FNa)–based wide-field fluorescence guidance were acquired for immediate intraoperative ex vivo optical biopsies with CLE. Hematoxylin-eosin–stained frozen section analysis of the same specimens served as the gold standard for blinded neuropathology comparison. FNa 2 to 5 mg/kg was administered upon induction of anesthesia, and FNa 5 mg/kg was injected for CLE contrast improvement. Histologic features were identified, and the diagnostic accuracy of CLE was assessed. Results Of 77 eligible patients, 47 patients with 122 biopsies were enrolled, including 32 patients with gliomas and 15 patients with other intracranial lesions. The positive predictive value of CLE optical biopsies was 97% for all specimens and 98% for gliomas. The specificity of CLE was 90% for all specimens and 94% for gliomas. The second FNa injection in seven patients, a mean of 2.6 h after the first injection, improved image quality and increased the percentage of accurately diagnosed images from 67% to 93%. Diagnostic CLE features of lesional glioma biopsies and normal brain were identified. Seventeen histologic features were identified. Conclusions Results demonstrated high specificity and positive predictive value of ex vivo intraoperative CLE optical biopsies and justify an in vivo intraoperative trial. This new portable, noninvasive intraoperative imaging technique provides diagnostic features to discriminate lesional tissue with high specificity and is feasible for incorporation into the fluorescence-guided surgery workflow, particularly for patients with invasive brain tumors.
COVID-19: A Challenge to Physiology of Aging

The death toll of the current COVID-19 pandemic is strongly biased toward the elderly. COVID-19 case fatality rate (CFR) increases with age exponentially, its doubling time being about 7 years, irrespective of countries and epidemic stages. The same age-dependent mortality pattern known as the Gompertz law is featured by the total mortality and its main constituents attributed to cardiovascular, metabolic, neurological, and oncological diseases. Among patients dying of COVID-19, most have at least one of these conditions, whereas none is found in most of those who pass it successfully. Thus, gerontology is indispensable in dealing with the pandemic, which becomes a benchmark for validating the gerontological concepts and advances. The two basic alternative gerontological concepts imply that either aging results from the accumulation of stochastic damage, or is programmed. Based on these different grounds, several putative anti-aging drugs have been proposed as adjuvant means for COVID-19 prevention and/or treatment. These proposals are reviewed in the context of attributing the molecular targets of these drugs to the signaling pathways between the sensors of resource availability and the molecular mechanisms that allocate resources to storage, growth and reproduction or to self-maintenance and repair. Each of the drugs appears to reproduce only a part of the physiological responses to reduced resource availability caused by either dietary calories restriction or physical activity promotion, which are the most robust means of mitigating the adverse manifestations of aging. In the pathophysiological terms, the conditions of the endothelium, which worsen as age increases and may be significantly improved by the physical activity, is a common limiting factor for the abilities to withstand both physical stresses and challenges imposed by COVID-19. However, the current anti-epidemic measures promote sedentary indoor lifestyles, at odds with the most efficient behavioral interventions known to decrease the vulnerability to both the severe forms of COVID-19 and the prevalent aging-associated diseases. To achieve a proper balance in public health approaches to COVID-19, gerontologists should be involved in crosstalk between virologists, therapists, epidemiologists, and policy makers. The present publication suggests a conceptual background for that.
Tests on the Accuracy and Scalability of the Full-Potential DFT Method Based on Multiple Scattering Theory

We investigate a reduced scaling full-potential DFT method based on the multiple scattering theory (MST) code MuST, which is released online (https://github.com/mstsuite/MuST) very recently. First, we test the accuracy by calculating structural properties of typical body-centered cubic (BCC) metals (V, Nb, and Mo). It is shown that the calculated lattice parameters, bulk moduli, and elastic constants agree with those obtained from the VASP, WIEN2k, EMTO, and Elk codes. Second, we test the locally self-consistent multiple scattering (LSMS) mode, which achieves reduced scaling by neglecting the multiple scattering processes beyond a cut-off radius. In the case of Nb, the accuracy of 0.5 mRy/atom can be achieved with a cut-off radius of 20 Bohr, even when small deformations are imposed on the lattice. Despite that the calculation of valence states based on MST exhibits linear scaling, the whole computational procedure has an overall scaling of about O(N1.6), due to the fact that the updating of Coulomb potential scales almost as O(N2). Nevertheless, it can be still expected that MuST would provide a reliable and accessible way to large-scale first-principles simulations of metals and alloys.
Monetary Policy with Reserves and CBDC: Optimality, Equivalence, and Politics

We analyze policy in a two-tiered monetary system. Noncompetitive banks issue deposits while the central bank issues reserves and a retail CBDC. Monies differ with respect to operating costs and liquidity. We map the framework into a baseline business cycle model with "pseudo wedges" and derive optimal policy rules: Spreads satisfy modified Friedman rules and deposits must be taxed or subsidized. We generalize the Brunnermeier and Niepelt (2019) result on the macro irrelevance of CBDC but show that a deposit based payment system requires higher taxes. The model implies annual implicit subsidies to U.S. banks of up to 0.8 percent of GDP during the period 1999-2017.
Dynamic correlation in the electron angular distribution in ionization of helium by ion impact

Single ionization of helium by proton impact is investigated in terms of a four-body distorted wave model. In this approximation both electrons are considered as active, being one of them ionized whereas the other remains in a residual target bound state. The influence of dynamic correlation between electrons is investigated by comparison with a four-body uncorrelated distorted wave model. Double differential cross sections as a function of the emission angle for fixed electron energies and different collision energies are presented.
The metabolism and excretion of lignocaine in man

The urinary excretion of lignocaine and monoethylglycinexylidide (megx) has been studied in man. The finding that megx is a major metabolite of lignocaine in man is discussed in relation to studies in animals reported by other workers. An analogue computer model was constructed to simulate the metabolism and excretion of lignocaine. By varying the model parameters it was possible to obtain good agreement between the calculated and empirical excretion data for both lignocaine and its metabolite megx. Because of this good agreement, the computer was used to predict body levels of the compounds after a dose of lignocaine.
Efficacy and Safety of Botulinum Toxin vs. Placebo in Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Major depressive disorder (MDD) is a serious mental disorder that represents a substantial public health problem. Several trials have been undertaken to investigate the role of botulinum toxin type A (BTX-A) in the treatment of MDD, but the conclusions were controversial. To examine the efficacy and safety of BTX-A vs. placebo on patients with a clinical diagnosis of MDD, we conducted this systematic review and meta-analysis. Methods: A systematic search was conducted for all relevant randomized controlled trials (RCTs) in PubMed and Web of Science from inception to June 17, 2020. All published studies that investigated the efficacy and safety of BTX-A injections on patients with a clinical diagnosis of MDD were included. The overall effect size was summarized using a random-effects meta-analysis model. The primary outcomes of the present meta-analysis were the changes in depressive rating scale at week 6 after BTX-A injection compared with placebo. The safety of BTX-A injections also was assessed. Results: Five RCTs with a total of 417 participants (189 patients in the BTX-A group, 228 patients in placebo group) were eligible in this meta-analysis. The results indicated an overall positive effect of BTX-A injections for reducing the depressive symptoms of patients with MDD (Hedges' g, −0.82; 95% CI, −1.38 to −0.27) with large effect size. Differences are likely explained by the dose of BTX-As and the gender of the participants. Our findings also highlighted that BTX-A injections were generally well-tolerated, with only mild and temporary adverse events reported. Conclusions: The present meta-analysis provides evidence that BTX-A injections are associated with a statistically significant improvement in depressive symptoms. BTX-A injections are generally safe and may provide a new, alternative option for the treatment of depression.
Mechanisms Underlying the Antidepressant Effect of Acupuncture via the CaMK Signaling Pathway

The CaMK pathway has been proven to play an important role in regulating cognitive function and emotional response. Acupuncture through the CaMK pathway improves depression-like behavior and the molecular mechanism related to its antidepressant remains to be explored. In this study, we aimed to determine whether the ability of acupuncture at Baihui (GV20) and Shenting (GV24) points to treat depression is related to the regulation of key proteins in the CaMK pathway. A rat model of depression was induced by chronic unpredicted mild stress (CUMS). Model rats in the electroacupuncture group were subjected to acupuncture at the Baihui (GV20) and Shenting (GV24) acupoints once a day for 20 min. Model rats in the fluoxetine group were gavaged with fluoxetine (1.8 mg/kg). Immunohistochemistry and Western blotting assays were used to evaluate immunoreactivity for and the protein expression levels of CaMKII, CaMKIV, and CaM. The results showed that electroacupuncture had a significant effect in rats with depression. Electroacupuncture and fluoxetine regulated the expression of key proteins in the CaMK signaling pathway, which is related to depression, in the hippocampi of rats. This indicates that acupuncture at Baihui (GV20) and Shenting (GV24) may alleviate depressive symptoms and reduce work- and life-related burdens and stress by regulating the CaMK signaling pathway.
Establishment of a Disease‐Drug Trial Model for Postmenopausal Osteoporosis: A Zoledronic Acid Case Study

Costly and lengthy clinical trials hinder the development of safe and effective treatments for postmenopausal osteoporosis. To reduce the expense associated with these trials, we established a mechanistic disease‐drug trial model for postmenopausal osteoporosis that can predict phase 3 trial outcome based on short‐term bone turnover marker data. To this end, we applied a previously developed model for tibolone to bisphosphonates using zoledronic acid as paradigm compound by (1) linking the mechanistic bone cell interaction model to bone turnover markers as well as bone mineral density in lumbar spine and total hip, (2) employing a mechanistic disease progression function, and (3) accounting for zoledronic acid's mechanism of action. Once developed, we fitted the model to clinical trial data of 581 postmenopausal women receiving (1) 5‐mg zoledronic acid in year 1 and saline in year 2, (2) 5‐mg zoledronic acid in year 1 and year 2, or (3) placebo (saline), calcium (500 mg), and vitamin D (400 IU). All biomarker data was fitted reasonably well, with no apparent bias or model misspecification. Age, years since menopause, and body mass index at baseline were identified as significant covariates. In the future, the model can be modified to explore the link between short‐term biomarkers and fracture risk.
Unveiling the Biogeography and Potential Functions of the Intestinal Digesta- and Mucosa-Associated Microbiome of Donkeys

The intestinal microbial composition and metabolic functions under normal physiological conditions in the donkey are crucial for health and production performance. However, compared with other animal species, limited information is currently available regarding the intestinal microbiota of donkeys. In the present study, we characterized the biogeography and potential functions of the intestinal digesta- and mucosa-associated microbiota of different segments of the intestine (jejunum, ileum, cecum, and colon) in the donkey, focusing on the differences in the microbial communities between the small and large intestine. Our results show that, Firmicutes and Bacteroidetes dominate in both the digesta- and mucosa-associated microbiota in different intestinal locations of the donkey. Starch-degrading and acid-producing (butyrate and lactate) microbiota, such as Lactobacillus and Sarcina, were more enriched in the small intestine, while the fiber- and mucin-degrading bacteria, such as Akkermansia, were more enriched in the large intestine. Furthermore, metabolic functions in membrane transport and lipid metabolism were more enriched in the small intestine, while functions for energy metabolism, metabolism of cofactors and vitamins, amino acid metabolism were more enriched in the large intestine. In addition, the microbial composition and functions in the digesta-associated microbiota among intestinal locations differed greatly, while the mucosal differences were smaller, suggesting a more stable and consistent role in the different intestinal locations. This study provides us with new information on the microbial differences between the small and large intestines of the donkey and the synergistic effects of the intestinal microbiota with host functions, which may improve our understanding the evolution of the equine digestive system and contribute to the healthy and efficient breeding of donkeys.
A Potential Mechanism of Sodium Channel Mediating the General Anesthesia Induced by Propofol

General anesthesia has revolutionized healthcare over the past 200 years and continues to show advancements. However, many phenomena induced by general anesthetics including paradoxical excitation are still poorly understood. Voltage-gated sodium channels (NaV) were believed to be one of the proteins targeted during general anesthesia. Based on electrophysiological measurements before and after propofol treatments of different concentrations, we mathematically modified the Hodgkin–Huxley sodium channel formulations and constructed a thalamocortical model to investigate the potential roles of NaV. The ion channels of individual neurons were modeled using the Hodgkin–Huxley type equations. The enhancement of propofol-induced GABAa current was simulated by increasing the maximal conductance and the time-constant of decay. Electroencephalogram (EEG) was evaluated as the post-synaptic potential from pyramidal (PY) cells. We found that a left shift in activation of NaV was induced primarily by a low concentration of propofol (0.3–10 μM), while a left shift in inactivation of NaV was induced by an increasing concentration (0.3–30 μM). Mathematical simulation indicated that a left shift of NaV activation produced a Hopf bifurcation, leading to cell oscillations. Left shift of NaV activation around a value of 5.5 mV in the thalamocortical models suppressed normal bursting of thalamocortical (TC) cells by triggering its chaotic oscillations. This led to irregular spiking of PY cells and an increased frequency in EEG readings. This observation suggests a mechanism leading to paradoxical excitation during general anesthesia. While a left shift in inactivation led to light hyperpolarization in individual cells, it inhibited the activity of the thalamocortical model after a certain depth of anesthesia. This finding implies that high doses of propofol inhibit the network partly by accelerating NaV toward inactivation. Additionally, this result explains why the application of sodium channel blockers decreases the requirement for general anesthetics. Our study provides an insight into the roles that NaV plays in the mechanism of general anesthesia. Since the activation and inactivation of NaV are structurally independent, it should be possible to avoid side effects by state-dependent binding to the NaV to achieve precision medicine in the future.
Channel-facilitated membrane transport: Transit probability and interaction with the channel

Transport of metabolites between cells and between subcellular compartments is facilitated by special protein channels that form aqueous pores traversing biological membranes. Accumulating evidence demonstrates that solute-specific channels display pronounced binding to the corresponding solutes. In this paper we rationalize this observation by showing that a wide and deep potential well inside the channel is able to greatly increase the transit probability of the particle through the channel. Using a one-dimensional diffusion model with radiation boundary conditions, we give exact analytical expressions for the particle translocation probabilities. We also run Brownian dynamics simulations to verify the model and the quantitative predictions of our theory.
British HIV Association guidelines on the management of opportunistic infection in people living with HIV: the clinical management of gastrointestinal opportunistic infections 2020

DR Chadwick RK Sutherland, S Raffe, ERM Pool and MBJ Beadsworth Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, UK, Regional Infectious Diseases Unit, NHS Lothian, Edinburgh, UK, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK, Mortimer Market Centre, Central and North West London NHS Foundation Trust, London, UK and Tropical and Infectious Disease Unit, Royal Liverpool University Hospital (Liverpool University Hospitals Foundation Trust), Liverpool, UK
Training and Transfer of Cue Updating in Older Adults Is Limited: Evidence From Behavioral and Neuronal Data

Cognitive control processes, such as updating task-relevant information while switching between multiple tasks, are substantially impaired in older adults. However, it has also been shown that these cognitive control processes can be improved by training interventions, e.g., by training in task switching. Here, we applied an event-related potential (ERP) approach to identify whether a cognitive training improves task-preparatory processes such as updating of relevant task goals. To do so, we applied a pretest-training-posttest design with eight training sessions. Two groups of older adults were either trained in task switching (treatment group) or in performing single tasks (control group) and we compared their performance to a group of untrained younger adults. To foster cue updating in the treatment group, we applied a cue-based switching task in which the two task cues were randomly selected prior to target presentation so that participants had time to prepare for the upcoming task. In contrast, the control group also received task cues but those were redundant as only one task had to be performed. We also examined whether training in cue updating during task switching can be transferred to a similar cognitive control task measuring updating of context information, namely a modified version of the AX-Continuous Performance Task (AX-CPT). The results revealed training-specific improvements in task switching, that is, a larger improvement in blocks requiring switching in comparison to single tasks at the behavioral level. In addition, training specific-effects were also found at the neuronal level. Older adults trained in cue updating while switching showed a reduction in mixing costs in the cue-related P3, indicating an improvement in preparatory updating processes. Additionally, P3 topography changed with training from a very broad to a parietally focused scalp distribution similar to the one found in younger adults. However, we did not obtain training-specific improvements in context updating in the AX-CPT neither at the behavioral level nor at the neuronal level. Results are discussed in the context of the ongoing debate on whether transfer of cognitive training improvements is possible.
The Prevalence of Pulmonary Hypertension Among Maintenance Dialysis Patients With ESRD and Its Associated Factors: A Retrospective Study

Aim: To determine the prevalence of pulmonary hypertension (PH) and its associated factors among end-stage renal disease (ESRD) patients who underwent maintenance dialysis. Methods: A total of 491 patients received echocardiography examinations and underwent pulmonary artery systolic pressure (PASP) assessments. A subgroup of 283 patients were subjected to plasma creatinine (Cr) and blood urea nitrogen concentration (BUN) tests, routine blood examinations and electrolyte analysis. First, we compared the differences in echocardiographic, Cr and BUN, blood routine and electrolyte parameters between PH and non-PH groups. The correlations between PASP and the parameters mentioned above were also analyzed. Furthermore, univariate and adjusted logistic regression analyses were performed to identify the independent associated factors. Results: The incidence of PH among ESRD patients who were treated with maintenance dialysis was 34.6%. Most of the echocardiographic parameters, including end-diastolic internal diameters of the left atrium, left ventricle, right atrium, and pulmonary artery, as well as interventricular septum mobility, left ventricular posterior wall mobility, fractional shortening, stroke volume and left ventricle ejection fraction (LVEF), were associated with PH. Furthermore, Mg2+ (p = 0.037) and Cl− (p = 0.043) were significantly associated with PASP. However, after adjustments were made in the regression analysis, only internal diameters of the left atrium, right atrium, and LVEF were independently associated with PH. Conclusion: PH is prevalent, with a relatively high incidence among ESRD patients who undergo maintenance dialysis. The sizes of the left and right atria as well as LVEF were independently associated with PH, but further cohort and basic mechanistic studies are needed to confirm this finding.