Miracle-dz/UniFAR-FTUs huggingface dataset:
Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs.

AIMS OF THE STUDY Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS This retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs. RESULTS After successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p <0.001), respectively, compared with patients treated with the standard of care. Neither experimental therapy was significantly associated with mortality. These additional hospital days amounted to 1010.77 additional days for hydroxychloroquine and hydroxychloroquine combined with lopinavir/ritonavir, resulting in an additional cost of US$ 2,492,214 (95%CI US$ 916,839–3,450,619). CONCLUSIONS Prescribing experimental therapies for COVID-19 was not associated with a reduced LOS and might have increased the pressure put on healthcare systems.
A comparison of the effects of Forsus appliances with and without temporary anchorage devices for skeletal Class II malocclusion.

OBJECTIVES To compare the effects of Forsus appliances with and without temporary anchorage devices (TADs) for patients with skeletal Class II malocclusion. MATERIALS AND METHODS Through a predefined search strategy, electronic searching was conducted in PubMed, Embase, Web of Science, CENTRAL, ProQuest Dissertations & Theses, and SIGLE with no language restrictions. Eligible study selection, data extraction, and evaluation of risk of bias (Cochrane Collaboration tool) were conducted by two authors independently and in duplicate. Any disagreement was solved by discussion or judged by a third reviewer. Statistical pooling, sensitivity analysis, subgroup analysis, and assessment of small-study effects were conducted by using Comprehensive Meta-Analysis and Stata 12.0. Heterogeneity was analyzed for different types of study designs, TADs, and radiographic examinations. RESULTS Electronic search yielded a total of 256 studies after removing duplicates. Among them, six studies were finally included. All articles were of high quality. The pooled mean differences were -0.27 (95% confidence interval [CI]: -0.59, 0.05) for SNA, 0.58 (95% CI: -0.07, 1.23) for SNB, -0.86 (95% CI: -1.74, -0.03) for ANB, 1.63 (95% CI: 0.46, 2.80) for Co-Po, 0.75 (95% CI: 0.28, 1.23) for SN-MP, -7.56 (95% CI: -11.37, -3.76) for L1-MP, 0.47 (95% CI: -0.98, 1.91) for overjet, 0.39 (95% CI: -0.57, 1.35) for overbite, -1.84 (95% CI: -5.15, 1.47) for SN-OP, and 4.97 (95% CI: -1.22, 11.17) for nasolabial angle. CONCLUSIONS TADs (especially miniplates) were able to eliminate dental adverse effects of Forsus appliances for correction of skeletal Class II malocclusion.
Anti-Tumor Activity of Hypericum perforatum L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics

In this paper we review the mechanisms of the antitumor effects of Hypericum perforatum L. (St. John’s wort, SJW) and its main active component hyperforin (HPF). SJW extract is commonly employed as antidepressant due to its ability to inhibit monoamine neurotransmitters re-uptake. Moreover, further biological properties make this vegetal extract very suitable for both prevention and treatment of several diseases, including cancer. Regular use of SJW reduces colorectal cancer risk in humans and prevents genotoxic effects of carcinogens in animal models. In established cancer, SJW and HPF can still exert therapeutic effects by their ability to downregulate inflammatory mediators and inhibit pro-survival kinases, angiogenic factors and extracellular matrix proteases, thereby counteracting tumor growth and spread. Remarkably, the mechanisms of action of SJW and HPF include their ability to decrease ROS production and restore pH imbalance in tumor cells. The SJW component HPF, due to its high lipophilicity and mild acidity, accumulates in membranes and acts as a protonophore that hinders inner mitochondrial membrane hyperpolarization, inhibiting mitochondrial ROS generation and consequently tumor cell proliferation. At the plasma membrane level, HPF prevents cytosol alkalization and extracellular acidification by allowing protons to re-enter the cells. These effects can revert or at least attenuate cancer cell phenotype, contributing to hamper proliferation, neo-angiogenesis and metastatic dissemination. Furthermore, several studies report that in tumor cells SJW and HPF, mainly at high concentrations, induce the mitochondrial apoptosis pathway, likely by collapsing the mitochondrial membrane potential. Based on these mechanisms, we highlight the SJW/HPF remarkable potentiality in cancer prevention and treatment.
History of indigenous Trypanosoma cruzi infection in humans, animals and triatomines in California, USA

This historical review highlights previously undescribed potential foci for sylvatic and domestic locally acquired Chagas disease in California. The review starts in the 1910s, when Trypanosoma cruzi was first discovered through scientific triatomine investigations. Next, the natural transition around the mid‐1900s into clinical investigations of the domestic and peridomestic environments and their epidemiologic profiles is detailed. The review closes with the shift to applied genetic, diagnostic and scientific applications surrounding Chagas disease infected individuals in the state. Throughout the course of the review, transmission foci and their unique clinical and epidemiologic characteristics are described. This in‐depth review has merit for clinicians, veterinarians and public health officials working with vector‐borne diseases in the southwestern USA.
Perioperative Optimization of Senior Health in Spine Surgery: Impact on Postoperative Delirium

Delirium is a common postoperative complication in geriatric patients, especially in those with underlying risk factors. Multicomponent nonpharmacologic interventions are effective in preventing delirium, however, implementation of these measures is variable in perioperative care. The aim of our study was to assess the impact of our Perioperative Optimization of Senior Health Program (UTSW POSH) on postoperative delirium in patients undergoing elective spine surgery.
Influence of Roasting Temperatures on the Antioxidant Properties, β-Glucan Content, and Volatile Flavor Profiles of Shiitake Mushroom

The objective of this study was to determine the influence of roasting conditions on the volatile flavor profiles and functional properties of shiitake mushrooms. Six different roasting temperatures between 80 °C and 180 °C with 20 °C increments were selected, and mushrooms were roasted for 60 min in a conventional oven. Roasting shiitake mushroom at 140 °C showed the highest levels of antioxidant activities including 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhidrazyl (DPPH) radical scavenging activities, total phenols and polyphenol contents. The β-glucan ranged from 34.85% to 41.49%, and it was highest when the mushrooms were roasted at 120 °C, followed by 140 °C. Instrumental flavor analysis was conducted by Gas Chromatography using Purge and Trap, and identification of compounds were produced by NIST library. Twenty-six volatile flavor compounds were identified. The concentrations of pyrazines and furans increased with increased roasting temperatures. Shiitake mushrooms roasted at 160 °C for 60 min had the most diverse volatile flavor compound profiles. This study revealed how roasting temperatures can modulate antioxidant, functional (β-glucan) and flavor benefits.
Microbiological profile of diabetic foot ulcers in Kuwait

Introduction Diabetic foot ulcers (DFU) and infection (DFI) are a major diabetes-related problem around the world due to the high prevalence of diabetes in the population. The aim of our study was to determine the microbiological profile of infected ulcers in patients attending Dasman Diabetes Institute (DDI) clinics in Kuwait and to analyze the distribution of microbial isolates according to wound grade, sex, age and diabetes control. Methods We collected and analyzed clinical data and samples from 513 diabetic patients with foot ulcers referred to our podiatry clinic at DDI from Jan 2011 till Dec 2017. Results We show a higher prevalence of DFU in men than in women, and a greater percentage of DFU occurred in men at an earlier age (p<0.05). Only about half of the DFU were clinically infected (49.3%) but 92% of DFU showed bacterial growth in the microbiological lab analysis. In addition, we isolated more monomicrobial (57.3%) than polymicrobial (34.8%) DFI and representing an average of 1.30 pathogens per patient. The presence of Gram-positive and Gram-negative strains was comparable between men and women regardless their age or glucose levels. Interestingly, more Gram-positive strains are present in ulcers without ischemia while more Gram-negative strains are present in ulcers with ischemia (p<0.05). While Staphylococcus aureus was common in infected ulcers without ischemia, Pseudomonas aeruginosa was predominant in ulcers with infection and ischemia, regardless of ulcer depth. Finally, a higher percentage of women has controlled HbA1c levels (19.41% versus 11.95% in men) and more women in this group displayed non-infected wounds (60.6% and 43.90% for women and men, respectively). Conclusion Our results provide an updated picture of the DFI patterns and antibiotics resistance in patients attending Dasman Diabetes Institute (DDI) clinics in Kuwait which might help in adopting the appropriate treatment of infected foot and improving clinical outcomes.
Longitudinal stability of medial temporal lobe connectivity is associated with tau-related memory decline

The relationship between Alzheimer’s disease (AD) pathology and cognitive decline is an important topic in the aging research field. Recent studies suggest that memory deficits are more susceptible to phosphorylated tau (Ptau) than amyloid-beta. However, little is known regarding the neurocognitive mechanisms linking Ptau and memory-related decline. Here, we extracted data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants with cerebrospinal fluid (CSF) Ptau collected at baseline, diffusion tensor imaging measure twice, 2 year apart, and longitudinal memory data over 5 years. We defined three age- and education-matched groups: Ptau negative cognitively unimpaired, Ptau positive cognitively unimpaired, and Ptau positive individuals with mild cognitive impairment. We found the presence of CSF Ptau at baseline was related to a loss of structural stability in medial temporal lobe connectivity in a way that matched proposed disease progression, and this loss of stability in connections known to be important for memory moderated the relationship between Ptau accumulation and memory decline.
Effect of Salinity and Rootstock on Concentration of Potassium, Calcium, Magnesium, Phosphorus, and Nitrate–Nitrogen in Thompson Seedless Grapevine

Abstract The effect of salinity on potassium (K), calcium (Ca), magnesium (Mg), phosphorus (P), and nitrate–nitrogen (NO3–N) concentration and partitioning was studied in a hydroponic culture of own-rooted grapevine, cultivar Thompson seedless (Vitis vinifera L.), or grafted onto the rootstocks 110R, 140Ru, 1103P, SO4, and 41B. Plants were grown in 25 L pots and exposed to salinity by irrigation for a period of 60 days with 50% Hoagland No. 2 nutrient solution also containing 5, 25, 50, or 100 mM NaCl. At the end of the stress period, concentrations of K, Ca, Mg, P, and NO3–N were measured in leaf blades, leaf petioles, shoots, trunk, and roots. Leaf blade, leaf petiole, and shoot P concentrations increased with salinity, whereas that of NO3–N and K decreased in all parts of the vine. Salinity had no effect on shoot Ca and Mg, trunk P and Mg, and root P, Ca, and Mg concentrations. Rootstock genotype significantly influenced the nutrient concentrations of different vine organs, except those of blade and root Ca, petiole Mg and NO3–N, shoot P and NO3–N, and trunk P and NO3–N.
Physical Activity and Low Glycemic Index Mediterranean Diet: Main and Modification Effects on NAFLD Score. Results from a Randomized Clinical Trial

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease worldwide, and lifestyle modification is the current standard treatment. The aim of the study was to estimate the effect of two different physical activity (PA) programs, a Low Glycemic Index Mediterranean Diet (LGIMD), and their combined effect on the NAFLD score as measured by FibroScan®. Methods: Moderate or severe NAFLD subjects (n = 144) were randomly assigned to six intervention arms during three months. Interventions arms were a control diet, LGIMD, aerobic activity program (PA1), combined activity program (PA2), and LGIMD plus PA1 or LGIMD plus PA2. The data were compared at baseline, at 45 days, and at 90 days. Analysis of variance was performed under the intention-to-treat principle. Results: There was a statistically significant reduction in the NAFLD score after 45 days of treatment in every working arm except for Arm 1 (control diet). After 90 days, the best results were shown by the intervention arms in which LGIMD was associated with PA: LGIMD plus PA1 (−61.56 95% CI −89.61, −33.50) and LGIMD plus PA2 (−38.15 95% CI −64.53, −11.77). Conclusion: All treatments were effective to reduce NAFLD scores, but LGIMD plus PA1 was the most efficient.
Cytokinin N-glucosides: Occurrence, Metabolism and Biological Activities in Plants

Cytokinins (CKs) are a class of phytohormones affecting many aspects of plant growth and development. In the complex process of CK homeostasis in plants, N-glucosylation represents one of the essential metabolic pathways. Its products, CK N7- and N9-glucosides, have been largely overlooked in the past as irreversible and inactive CK products lacking any relevant physiological impact. In this work, we report a widespread distribution of CK N-glucosides across the plant kingdom proceeding from evolutionary older to younger plants with different proportions between N7- and N9-glucosides in the total CK pool. We show dramatic changes in their profiles as well as in expression levels of the UGT76C1 and UGT76C2 genes during Arabidopsis ontogenesis. We also demonstrate specific physiological effects of CK N-glucosides in CK bioassays including their antisenescent activities, inhibitory effects on root development, and activation of the CK signaling pathway visualized by the CK-responsive YFP reporter line, TCSv2::3XVENUS. Last but not least, we present the considerable impact of CK N7- and N9-glucosides on the expression of CK-related genes in maize and their stimulatory effects on CK oxidase/dehydrogenase activity in oats. Our findings revise the apparent irreversibility and inactivity of CK N7- and N9-glucosides and indicate their involvement in CK evolution while suggesting their unique function(s) in plants.
Knockout of sodium channel Nax delays re‐epithelializathion of splinted murine excisional wounds

Mammalian wound healing is a carefully orchestrated process in which many cellular and molecular effectors respond in concert to perturbed tissue homeostasis in order to close the wound and re‐establish the skin barrier. The roles of many of these molecular effectors, however, are not entirely understood. Our lab previously demonstrated that the atypical sodium channel Nax (encoded by Scn7a) responds to wound‐induced epidermal dehydration, resulting in molecular cascades that drive pro‐inflammatory signaling. Acute inhibition of Nax was sufficient to attenuate dermatopathological symptoms in models of hypertrophic scar and dermatitis. To date, however, the role of Nax in excisional wound healing has not been demonstrated. Here we report development of a knockout mouse that lacks expression of functional Nax, and we demonstrate that lack of functional Nax results in deficient wound healing in a murine splinted excisional wound healing model. This deficiency in wound healing was reflected in impaired re‐epithelialization and decreased keratinocyte proliferation, a finding which was further supported by decreased proliferation upon Nax knockdown in HaCaT cells in vitro. Defective wound healing was observed alongside increased expression of inflammatory genes in the wound epidermis of Nax−/− mice, suggesting that mice lacking functional Nax retain the ability to undergo skin inflammation. Our observations here motivate further investigation into the roles of Nax in wound healing and other skin processes.
Determination of the 129I transmutation rate and 129I(n, 2n)128I correction using gas mass spectrometry

Two groups of 129I and 127I targets were analyzed using a gas quadrupole mass spectrometer (QMS) to determine the transmutation rates via the melting method. Sodium iodide was chosen to make the target. The iodine composition in the 129I targets is 82.7% 129I and 17.3% 127I. The transmutation rate of the 129I(n, γ)130I reaction was determined by measuring the 130Xe with QMS. An equivalent corrective method was brought out to correct the 129I(n, 2n)128I branch which is interfered with by the 127I(n, γ)128I reaction. And the correction formula was deduced in theory. For very little 128Xe from the 129I(n, 2n)128I reaction, the equivalent corrective method could not be suitable here. However, it is suitable for the mass of 128Xe from 129I(n,2n)128I reaction that reaches the accurately detective level of the mass spectrometry.
Long-term Survival After Minimally Invasive Versus Open Esophagectomy for Esophageal Cancer

Objectives: This study aimed to compare long-term survival following MIE versus OE for esophageal cancer using a nationwide propensity-score matched cohort. Summary of Background Data: MIE provides lower postoperative morbidity and mortality, and similar short-term oncological quality compared to OE. Methods: Data was acquired from the Dutch Upper Gastrointestinal Cancer Audit. Patients undergoing minimally invasive or open, transthoracic or transhiatal esophagectomy for primary esophageal cancer between 2011 and 2015 were included. A propensity-score matching analysis for MIE versus OE was performed separately for transthoracic and transhiatal esoph-agectomies. Results: A total of 1036 transthoracic MIE and OE patients, and 582 transhiatal MIE and OE patients were matched. Long-term survival was comparable for MIE and OE for both transthoracic and transhiatal procedures (5-year overall survival: transthoracic MIE 49.2% vs OE 51.1%, P 0.695; transhiatal MIE 48.4% vs OE 50.7%, P 0.832). For both procedures, MIE yielded more lymph nodes (transthoracic median 21 vs 18, P < 0.001; transhiatal 15 vs 13, P 0.007). Postoperative morbidity was comparable after transthoracic MIE and OE (60.8% vs 64.9%, P 0.177), with a reduced length of stay after transthoracic MIE (median 12 vs 15 days, P < 0.001). After transhiatal MIE, more postoperative complications (64.9% vs 56.4%, P 0.034) were observed, without subsequent difference in length of stay. Conclusion: Long-term survival after MIE was equivalent to open in both propensity-score matched cohorts of patients undergoing transthoracic or transhiatal esophageal resections. Transhiatal MIE was accompanied with more postoperative morbidity. Both transthoracic and transhiatal MIE resulted in a more extended lymphadenectomy.
Induction of Genomic Instability in a Primary Human Fibroblast Cell Line Following Low-Dose Alpha-Particle Exposure and the Potential Role of Exosomes

Simple Summary Exposure to the naturally occurring radioactive gas Radon, and the resulting alpha-particle emitting progeny, dominates human exposure and is the second largest cause of lung cancer after smoking. The work presented shows that not only can very low doses of alpha-particles produce DNA damage in normal HF19 fibroblast cells (detected using comet and micronuclei assays) in the irradiated cell population, but also results in an enhanced yield of DNA damage in the progeny of these cells out to 10 and even 20 population doublings. This persistent elevation of DNA damage is consistent with genomic instability, a well-recognised feature of many tumours with its ability to generate genetic diversity in the dividing population. Environmental exposure is normally associated with a small fraction of cells being irradiated with a single alpha-particle, while the vast majority of cells remain unirradiated. Here, we demonstrate an enhanced yield of DNA damage observed at 10 and 20 population doublings even when less than 1% of the cell population is traversed, with a response similar to that observed when essentially all cells are irradiated. The finding also highlights the potential of exosomes produced by irradiated cells contributing to DNA damage observed in unirradiated bystander cells. Abstract Purpose: To study the induction of genomic instability (GI) in the progeny of cell populations irradiated with low doses of alpha-particles and the potential role of exosome-encapsulated bystander signalling. Methods: The induction of GI in HF19 normal fibroblast cells was assessed by determining the formation of micronuclei (MN) in binucleate cells along with using the alkaline comet assay to assess DNA damage. Results: Low dose alpha-particle exposure (0.0001–1 Gy) was observed to produce a significant induction of micronuclei and DNA damage shortly after irradiation (assays performed at 5 and 1 h post exposure, respectively). This damage was not only still evident and statistically significant in all irradiated groups after 10 population doublings, but similar trends were observed after 20 population doublings. Exosomes from irradiated cells were also observed to enhance the level of DNA damage in non-irradiated bystander cells at early times. Conclusion: very low doses of alpha-particles are capable of inducing GI in the progeny of irradiated cells even at doses where <1% of the cells are traversed, where the level of response was similar to that observed at doses where 100% of the cells were traversed. This may have important implications with respect to the evaluation of cancer risk associated with very low-dose alpha-particle exposure and deviation from a linear dose response.