Miracle-dz/UniFAR-FTUs huggingface dataset:
Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India (SPRINT INDIA) study protocol

Rationale Recurrent stroke, cardiovascular morbidity, and mortality are important causes of poor outcome in patients with index stroke. Despite the availability of best medical management recurrent stroke occur in up to 15–20% of patients with stroke in India. Education for stroke prevention could be a strategy to prevent recurrent strokes. Hypothesis We hypothesize that a structured semi-interactive stroke prevention package can reduce the risk of recurrent strokes, acute coronary artery syndrome, and death in patients with sub-acute stroke at the end of one year. Design Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in INDIA (SPRINT INDIA) is a multi-center stroke trial involving 25 centers under the Indian Stroke Clinical Trial Network. Patients with first ever sub-acute stroke within two days to three months of onset, age 18–85 years, mRS <5, showing recent stroke in imaging are included. Participants or caregivers able to read and complete tasks suggested in a stroke prevention workbook and have a cellular device for receiving short message service and watching videos. A total of 5830 stroke patients speaking 11 different languages are being randomized to intervention or control arm. Patients in the intervention arm are receiving a stroke prevention workbook, regular educational short messages, and videos. All patients in the control arm are receiving standard of care management. Summary Structured semi-interactive stroke prevention package may reduce the risk of recurrent strokes, acute coronary artery syndrome, and death in patients with sub-acute stroke. Trial registration This trial is registered with clinicaltrials.gov (NCT03228979) and CTRI (Clinical Trial Registry India; CTRI/2017/09/009600).
An in vivo RNAi screen uncovers the role of AdoR signaling and adenosine deaminase in controlling intestinal stem cell activity

Significance Regulation of stem cells by microenvironment signals is important to maintain epithelial homeostasis. Using a quantitative readout, we screened for receptor genes that affect the intestinal stem cell pool size in the adult Drosophila midgut. The top candidate of our screen, AdoR, underscores the importance of purinergic signaling in controlling ISC activity. Furthermore, we identified a pivotal role of an enterocyte-derived metabolic enzyme, Adgf-A, in limiting the activity of extracellular adenosine and shaping the ISC microenvironment. Metabolites are increasingly appreciated for their roles as signaling molecules. To dissect the roles of metabolites, it is essential to understand their signaling pathways and their enzymatic regulations. From an RNA interference (RNAi) screen for regulators of intestinal stem cell (ISC) activity in the Drosophila midgut, we identified adenosine receptor (AdoR) as a top candidate gene required for ISC proliferation. We demonstrate that Ras/MAPK and Protein Kinase A (PKA) signaling act downstream of AdoR and that Ras/MAPK mediates the major effect of AdoR on ISC proliferation. Extracellular adenosine, the ligand for AdoR, is a small metabolite that can be released by various cell types and degraded in the extracellular space by secreted adenosine deaminase. Interestingly, down-regulation of adenosine deaminase-related growth factor A (Adgf-A) from enterocytes is necessary for extracellular adenosine to activate AdoR and induce ISC overproliferation. As Adgf-A expression and its enzymatic activity decrease following tissue damage, our study provides important insights into how the enzymatic regulation of extracellular adenosine levels under tissue-damage conditions facilitates ISC proliferation.
Feasibility of imaging 90Y microspheres at diagnostic activity levels for hepatic radioembolization treatment planning

Purpose Prior to 90Y hepatic radioembolization, a dosage of 99mTc‐macroaggregated albumin (99mTc‐MAA) is administered to simulate the distribution of the 90Y‐loaded microspheres. This pretreatment procedure enables lung shunt estimation, detection of potential extrahepatic depositions, and estimation of the intrahepatic dose distribution. However, the predictive accuracy of the MAA particle distribution is often limited. Ideally, 90Y microspheres would also be used for the pretreatment procedure. Based on previous research, the pretreatment activity should be limited to the estimated safety threshold of 100 MBq, making imaging challenging. The purpose of this study was to evaluate the quality of intra‐ and extrahepatic imaging of 90Y‐based pretreatment positron emission tomography/computed tomography (PET/CT) and quantitative single photon emission computed tomography (SPECT)/CT scans, by means of phantom experiments and a patient study. Methods An anthropomorphic phantom with three extrahepatic depositions was filled with 90Y chloride to simulate a lung shunt fraction (LSF) of 5.3% and a tumor to nontumor ratio (T/N) of 7.9. PET /CT (Siemens Biograph mCT) and Bremsstrahlung SPECT/CT (Siemens Symbia T16) images were acquired at activities ranging from 1999 MBq down to 24 MBq, representing post‐ and pretreatment activities. PET/CT images were reconstructed with the clinical protocol and SPECT/CT images were reconstructed with a quantitative Monte Carlo‐based reconstruction protocol. Estimated LSF, T/N, contrast to noise ratio of all extrahepatic depositions, and liver parenchymal and tumor dose were compared with the phantom ground truth. A clinically reconstructed SPECT/CT of 150 MBq 99mTc represented the current clinical standard. In addition, a 90Y pretreatment scan was simulated for a patient by acquiring posttreatment PET/CT and SPECT/CT data with shortened acquisition times. Results At an activity of 100 MBq 90Y, PET/CT overestimated LSF [+10 percentage point (pp)], underestimated liver parenchymal dose (−3 Gy/GBq), and could not detect the extrahepatic depositions. SPECT/CT more accurately estimated LSF (−0.7 pp), parenchymal dose (−0.3 Gy/GBq) and could detect all three extrahepatic depositions. 99mTc SPECT/CT showed similar accuracy as 90Y SPECT/CT (LSF: +0.2 pp, parenchymal dose: +0.4 Gy/GBq, all extrahepatic depositions visible), although the noise level in the liver compartment was considerably lower for 99mTc SPECT/CT compared to 90Y SPECT/CT. The patient’s SPECT/CT simulating a pretreatment 90Y procedure accurately represented the posttreatment 90Y microsphere distribution. Conclusions Quantitative SPECT/CT of 100 MBq 90Y could accurately estimate LSF, T/N, parenchymal and tumor dose, and visualize extrahepatic depositions.
Comparison of the Perioperative and Postoperative Outcomes of Ileal Conduit and Cutaneous Ureterostomy: A Propensity Score-Matched Analysis

Introduction: To compare perioperative and postoperative outcomes related to urinary diversion (UD) between ileal conduit and cutaneous ureterostomy following open radical cystectomy (ORC). Methods: This retrospective study included 232 patients with bladder cancer who underwent ORC and subsequent UD (ileal conduit, n = 123; cutaneous ureterostomy, n = 109) at Kobe University and related hospitals between January 2007 and December 2016. A propensity score method was used to adjust the preoperative status of the two groups, and the perioperative and postoperative outcomes were compared between matched cohorts. In addition, we evaluated several factors predicting renal deterioration. Results: In the matched cohorts, 87 patients were included in each group. While the operative time and postoperative fasting periods were significantly longer in patients with ileal conduit in comparison to those with cutaneous ureterostomy (both p < 0.001), there were no differences in blood loss or duration of hospitalization. Although the incidence of grade ≥III perioperative complications was similar between the two groups, the incidence of postoperative recurrent pyelonephritis in the cutaneous ureterostomy group was significantly higher than that in the ileal conduit group (25.3 and 11.4%, respectively; p = 0.030), and cutaneous ureterostomy was identified as a significant predictor of a decrease in the estimated glomerular filtration rate with an odds ratio of 2.13 (95% confidence interval, 1.19–3.85; p = 0.010). Conclusions: The perioperative safety of ileal conduit was comparable to that of cutaneous ureterostomy, and cutaneous ureterostomy was a significant risk factor for pyelonephritis and subsequent renal deterioration, suggesting that ileal conduit may be preferable to cutaneous ureterostomy.
Infectious Complications of Acute Pancreatitis

AbstractIn most cases, acute pancreatitis is a self-limited condition that improves with supportive treatment. In 15% to 20%, severe acute pancreatitis develops, characterized by necrosis, multiorgan failure, infection, and other complications. There is an early and a late peak of severity in the natural course of acute pancreatitis. Pancreatic infections occur in 3 settings: free fluid collections, pseudocysts, and necrosis. The main mechanism of infection is translocation of microbes from the gut. Infection may be suggested by gas bubbles within pancreatic tissue or fluid collections seen with computed tomography or magnetic resonance imaging, as well as laboratory markers such as procalcitonin and IL-8. However, accurate diagnosis and confirmation requires guided needle aspiration of the infected fluid or tissue. Use of prophylactic antibiotics does not confer any mortality benefit. Infected fluid collections are generally treated with percutaneous or endoscopic drainage. Infected necrosis usually requires surgical intervention, but this should be delayed for at least 2 weeks after the onset of acute pancreatitis, allowing for better demarcation of the necrotic tissue from the viable pancreatic parenchyma. In select cases of infected necrosis, there may be a role for conservative treatment, but this needs to be further studied.
The transdermal performance, pharmacokinetics, and anti-inflammatory pharmacodynamics evaluation of harmine-loaded ethosomes

Abstract Harmine (HAR) is a β-carboline alkaloid with anti-inflammatory and antipruritic effect. However, the low bioavailability and side effects of HAR severely limited its clinical application. The main objective of this study was to develop harmine-loaded ethosomes (HLE) drug delivery system for topical application to treat inflammation. HLE were obtained by ethanol injection method and characterized. The morphology of HLE was evaluated by transmission electron microscopy (TEM). HLE exhibited a good biocompatibility with human embryonic skin fibroblasts and rat skin. The in vitro skin penetration studies showed that HLE had the greatest skin deposition than harmine-loaded liposomes (HLL) and harmine solution (HS). In vivo pharmacokinetic study demonstrated that AUC(0–∞) and Cmax of HLE in subcutaneous tissues were much higher than that of in blood. Moreover, for convenience of fixing on skin, HLE were mixed with gel. HLE gel significantly inhibited the overexpression of inflammation cytokines prostaglandin E2, interleuking (IL)-1β, nitric oxide, and tumor necrosis factor-alpha (TNF-α) in the inflammation model of rat paw edema compared with HS gel. In short, HLE was promising formulation for topical delivery in treatment of inflammatory diseases.
Central systolic blood pressure increases with aortic stiffness.

OBJECTIVES Central systolic blood pressure (CSBP) is the pressure in the root of aorta, which directly influences organs such as brain, heart and kidneys and is related to organ damage. Its value increases with the aortic stiffness. The aim of this study was to analyze the relationships of CSBP to aortic stiffness parameters. METHODS Central blood pressure (BP) and related parameters were measured by Arteriograph, working based on oscillometric principle, using pulse wave analysis (PWA) approach. We examined 123 patients (69 females, 54 males) with a primary hypertension. RESULTS Using a linear correlation analysis, we found that CSBP was correlated to aortic pulse wave velocity (PWV), aortic and brachial pulse pressure (PP), aortic augmentation index, return time of reflected pressure wave (RT) and aortic and brachial augmentation indexes. Multivariate analysis defines the aortic pulse pressure (PPao) as the most powerful parameter influencing CSBP. By an individual analysis of BP in each patient separately, we defined two different types of central hemodynamics; those with a higher CSBP than brachial SBP occur in stiffer aorta. CONCLUSION The CSBP increases with aortic PP, the most powerful stiffness parameter of aorta. Higher CSBP than brachial SBP usually accompanies a stiffer aorta (Tab. 5, Ref. 19).
Depression and sleep quality in psoriatic patients: impact of psoriasis severity

Abstract Background: Psoriatic patients often display depression and sleep disturbances. In previous research, we found high rates of depression and poor sleep quality among psoriatic patients, unrelated to psoriasis severity. However, these results referred to a sample mainly composed of patients under remission. Aim: To compared the prevalence of depression and sleep disturbances in patients suffering from mild versus moderate-tosevere plaque psoriasis, also investigating the association between psoriasis severity and psychopathological variables. Keypoints Psoriasis affects the patients’ psychophysical health. Depressive symptoms and/or sleep disturbances are frequent among psoriatic patients. This study investigates these issues comparing the sub-populations of mild and moderate-to-severe psoriatic patients, with special attention to the association between sleep and pruritus. In clinical practice, the link between psychopathological disturbances and psoriasis should not be underestimated.
Initial phospholipid-dependent Irgb6 targeting to Toxoplasma gondii vacuoles mediates host defense

Irgb6 has a role in the cell-autonomous response against T. gondii and involves ubiquitination and breakdown of vacuoles via binding of a specific phospholipid on the parasitophorous vacuole membrane. Toxoplasma gondii is an obligate intracellular protozoan parasite capable of infecting warm-blooded animals by ingestion. The organism enters host cells and resides in the cytoplasm in a membrane-bound parasitophorous vacuole (PV). Inducing an interferon response enables IFN-γ–inducible immunity-related GTPase (IRG protein) to accumulate on the PV and to restrict parasite growth. However, little is known about the mechanisms by which IRG proteins recognize and destroy T. gondii PV. We characterized the role of IRG protein Irgb6 in the cell-autonomous response against T. gondii, which involves vacuole ubiquitination and breakdown. We show that Irgb6 is capable of binding a specific phospholipid on the PV membrane. Furthermore, the absence of Irgb6 causes reduced targeting of other effector IRG proteins to the PV. This suggests that Irgb6 has a role as a pioneer in the process by which multiple IRG proteins access the PV. Irgb6-deficient mice are highly susceptible to infection by a strain of T. gondii avirulent in wild-type mice.
Urban oxidation flow reactor measurements reveal significant secondary organic aerosol contributions from volatile emissions of emerging importance.

Mobile sampling studies have revealed enhanced levels of secondary organic aerosol (SOA) in source-rich urban environments. While these enhancements can be from rapidly-reacting vehicular emissions, it was recently hypothesized that non-traditional emissions (volatile chemical products and upstream emissions) are emerging as important sources of urban SOA. We tested this hypothesis by using gas and aerosol mass spectrometry coupled with an oxidation flow reactor (OFR) to characterize pollution levels and SOA potentials in environments influenced by traditional emissions (vehicular, biogenic), and non-traditional emissions (e.g., paint fumes). We used two SOA models to assess contributions of vehicular and biogenic emissions to our observed SOA. The largest gap between observed and modeled SOA potential occurs in the morning-time urban street canyon environment, for which our model can only explain half of our observation. Contributions from VCP emissions (e.g., personal care products) are highest in this environment, suggesting that VCPs are an important missing source of precursors that would close the gap between modeled and observed SOA potential. Targeted OFR-oxidation of non-traditional emissions shows that these emissions have SOA potentials that are similar, if not larger, compared to vehicular emissions. Laboratory experiments reveal large differences in SOA potentials of VCPs, implying the need for further characterization of these non-traditional emissions.
Time-of-day variation on performance measures in repeated-sprint tests: a systematic review

ABSTRACT The lack of standardization of methods and procedures have hindered agreement in the literature related to time-of-day effects on repeated sprint performance and needs clarification. Therefore, the aim of the present study was to investigate and systematically review the evidence relating to time-of-day based on performance measures in repeated-sprints. The entire content of PubMed (MEDLINE), Scopus, SPORTDiscus® (via EBSCOhost) and Web of Science was searched. Only experimental research studies conducted in male adult participants aged ≥18yrs, published in English before June 2019 were included. Studies assessing repeated-sprints between a minimum of two time-points during the day (morning versus evening) were deemed eligible. The primary search revealed that a total of 10 out of 112 articles were considered eligible and subsequently included. Seven articles were deemed strong and three moderate quality. Eight studies found repeated-sprint performance across the first, first few, or all sprints, to increase in favor of the evening. The magnitude of difference is dependent on the modality and the exercise protocol used. The non-motorized treadmill established an average 3.5–8.5% difference in distance covered, average and peak velocity, and average power, across all sprints in three studies and in peak power in two studies. In cycling, power output differed across all sprints by 6.0% in one study and 8.0% for the first sprint only in five studies. All four studies measuring power decrement values (i.e. rate of fatigue) established differences up to 4.0% and two out of five studies established total work to be significantly higher by 8.0%. Repeated-sprint performance is affected by time-of-day with greater performance in the late/early afternoon. The magnitude is dependent on the variable assessed and the mode of exercise. There is a clear demand for more rigorous investigations which control factors that specifically relate to investigations of time-of-day and are specific to the sport of individuals.
Unexpected intracellular biodegradation and recrystallization of gold nanoparticles

Significance While gold nanoparticles are at the core of an increasing range of medical applications, their fate in the organism has barely been studied so far. Because of their chemical inertness, common belief is that gold nanoparticles remain endlessly intact in tissues. We show that 4- to 22-nm gold nanoparticles are actually degraded in vitro by cells, with a faster degradation of the smallest size. Transcriptomics studies reveal the active role of cell lysosome into this biodissolution. Furthermore, we point out that the released gold recrystallizes into biopersistent nanostructures. Interestingly, these degradation products are similar to previously observed gold deposits in human tissues after gold salts treatment for rheumatoid arthritis, underlying a common metabolism between gold nanoparticles and ionic gold. Gold nanoparticles are used in an expanding spectrum of biomedical applications. However, little is known about their long-term fate in the organism as it is generally admitted that the inertness of gold nanoparticles prevents their biodegradation. In this work, the biotransformations of gold nanoparticles captured by primary fibroblasts were monitored during up to 6 mo. The combination of electron microscopy imaging and transcriptomics study reveals an unexpected 2-step process of biotransformation. First, there is the degradation of gold nanoparticles, with faster disappearance of the smallest size. This degradation is mediated by NADPH oxidase that produces highly oxidizing reactive oxygen species in the lysosome combined with a cell-protective expression of the nuclear factor, erythroid 2. Second, a gold recrystallization process generates biomineralized nanostructures consisting of 2.5-nm crystalline particles self-assembled into nanoleaves. Metallothioneins are strongly suspected to participate in buildings blocks biomineralization that self-assembles in a process that could be affected by a chelating agent. These degradation products are similar to aurosomes structures revealed 50 y ago in vivo after gold salt therapy. Overall, we bring to light steps in the lifecycle of gold nanoparticles in which cellular pathways are partially shared with ionic gold, revealing a common gold metabolism.
Parental somatogonadal COL2A1 mosaicism contributes to intrafamilial recurrence in a family with type 2 collagenopathy

The COL2A1 gene encodes the alpha‐1 chain of procollagen type 2. Pathogenic variants in the COL2A1 gene are associated with several different types of skeletal dysplasia collectively known as type 2 collagenopathies. Type 2 collagenopathies have an autosomal dominant inheritance. Some germline or somatogonadal mosaicism cases have been reported. We investigated whether somatogonadal mosaicism occurred in a family with two children suspected of type 2 collagenopathies or related diseases. First, we detected a pathogenic variant in the COL2A1 gene in the two affected children by whole exome sequencing (WES). Next, we performed targeted deep sequencing to their parents without the variant by WES. A low level of COL2A1 mosaicism was revealed in the mother's tissues. We concluded that the mother had somatogonadal mosaicism with the COL2A1 mutation arose in the epiblast, and that the intrafamilial recurrence rate of the disease by the somatogonadal mosaicism was higher than by the germline mosaicism. This report suggests that parental low‐level mosaicism should be evaluated in those parents with children carrying de novo germline mutations and the targeted deep sequencing is useful to detect them.