Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Locally Administered Fibrinolytic Drugs Following Aneurysmal Subarachnoid Hemorrhage : A Meta-Analysis with Eight Randomized Controlled Studies

Objective Rapid dissolution of blood clots reduces vasospasm and hydrocephalus after subarachnoid hemorrhage (SAH), and locally administered fibrinolytic drugs (LAFDs) could facilitate the dissolution. However, the efficacy of LAFDs remains controversial. The aim of this meta-analysis was to determine the efficacy of LAFDs for vasospasm and hydrocephalus and in clinical outcomes. Methods From PubMed, EMBASE, and Cochrane database, data were extracted by two authors. Meta-analysis was performed using a random effect model. Inclusion criteria were patients who had LAFDs with urokinase-type or recombinant tissue-plasminogen activator after SAH in comparison with medically untreated patients with fibrinolytic drugs. We only included randomized controlled trials (RCTs) in this analysis. The outcomes of interest were vasospasm, hydrocephalus, mortality, and 90-day unfavorable functional outcome. Results Data from eight RCTs with 550 patients were included. Pooled-analysis revealed that the LAFDs were significantly associated with lower rates of vasospasm (LAFDs group vs. control group, 26.5% vs. 39.2%; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.32–0.73); hydrocephalus (LAFDs group vs. control group, 26.0% vs. 31.6%; OR, 0.54; 95% CI, 0.32–0.91); and mortality (LAFDs group vs. control group, 10.5% vs. 15.7%; OR, 0.58; 95% CI, 0.34–0.99). The proportion of 90-day unfavorable outcomes was lower in the LAFDs group (LAFDs group vs. control group, 32.7% vs. 43.5%; OR, 0.55; 95% CI, 0.37–0.80). Conclusion This meta-analysis with eight RCTs indicated that LAFDs were significantly associated with lower rates of vasospasm and hydrocephalus after SAH. Thus, LAFDs could consequently reduce mortality and improve clinical outcome after SAH.
Osteopathy students profile in Italy: A cross sectional census

Introduction The Osteopathy Students Analysis (OSA) aims to profile osteopathy students in Italy as a target population in terms of sociodemographic characteristics, geographical distribution, health status, and previous and ongoing education specifications. Materials and methods The OSA used a cross-sectional design. A Web-based survey was distributed to the Italian Osteopathic Education Institutions (OEIs). The OSA survey was composed of items organised into four sections: 1. Sociodemographic characteristics (11 items); 2. Geographical distribution (5 items); 3. Health status (3 items); 4. Previous and ongoing education specifications (16 items). A descriptive sample population analysis was performed. Dichotomous and categorical variables were presented as frequencies and percentages, and continuous variables were displayed as means and standard deviations. Some variables were analysed using a pentenary distribution. Results 49 out of the 61 OEIs identified matched the inclusion criteria, and among these, 22 accepted to propose the enrolment of their students into the study. The survey was administered to 4,720 students from all the participant OEIs. A total of 3,762 students responded to the survey, accounting for an estimated response rate of 53.7%. The majority of respondents were men (54%), with an average age of 26.9 ± 6.5 years. Almost the totality of the sample was composed of the European ethnic group (99.1%). Respondents were predominantly born in Italy (97.2%). The majority of the sample reported being in good (49.5%) to excellent (38.6%) health. To date, osteopathy students are almost evenly distributed between the two types of curricula (T1 = 46.6%; T2 = 53.4%). Conclusions The OSA is the first study that aims to profile Italian osteopathy students as a target population in terms of sociodemographic characteristics, geographical distribution, health status, and previous and ongoing education specifications. Future studies should focus on investigating the correlation between the sociodemographic characteristics of students and their academic performance.
New data on tail lengths and variation along the caudal series in the non-avialan dinosaurs

The tails of non-avialan dinosaurs varied considerably in terms of overall length, total number of vertebrae, and gross form and function. A new dataset confirms that there is little or no consistent relationship between tail length and snout-sacrum length. Consequently, attempts to estimate one from the other are likely to be very error-prone. Patterns of changes in centra lengths across the caudal series vary among non-avian dinosaurs. However, some overarching patterns do emerge. A number of taxa show (anterior to posterior) a series of short centra, followed by a series of longer centra, with the remainder of the tail consisting of a long series of centra tapering in length. This pattern is consistent with functional constraints, and the anterior series of longer centra are coincident with the major attachments of femoral musculature. This pattern is not present in many basal taxa and may have evolved independently in different dinosaurian groups, further suggesting functional importance.
Lycorine inhibits cell proliferation, migration and invasion, and primarily exerts in vitro cytostatic effects in human colorectal cancer via activating the ROS/p38 and AKT signaling pathways

Colorectal cancer (CRC) is a life-threatening malignant tumor of the digestive tract. Diverse gene mutations and complicated alterations to the signaling pathways in CRC lead to heterogeneity in response to chemotherapy. Moreover, anticancer drugs for CRC chemotherapy are limited due to adverse events. Therefore, developing more effective, tolerable and safe drugs for the treatment of CRC is important. The present study aimed to investigate the effect of lycorine on human CRC cell proliferation, migration, invasion, apoptosis, cell cycle distribution, as well as the underlying molecular mechanism. The crystal violet staining and MTT assay results demonstrated that lycorine suppressed cell proliferation in a dose- and time-dependent manner in the three CRC cell lines, HCT116, LoVo and SW480. Similarly, verified by performing wound healing and Transwell assays, lycorine significantly inhibited HCT116 and LoVo cell migration and invasion in vitro compared with the control group. In LoVo cells, the protein expression levels of matrix metallopeptidases, snail family transcriptional repressor 1, Vimentin and N-cadherin were significantly downregulated, whereas the protein expression levels of E-cadherin were significantly upregulated by lycorine treatment compared with the control group. The Hoechst 33258 staining and flow cytometry assay results indicated that lycorine mediated its cytostatic effect on CRC cells potentially via inducing cell cycle arrest, but not apoptosis. Compared with the control group, lycorine significantly induced HCT116 cell cycle arrest at the G2/M phase, but significantly induced LoVo cell cycle arrest at the S and G2/M phases. Furthermore, lycorine significantly downregulated the protein expression levels of cyclin D1 and cyclin E1, but significantly increased p21 and Smad4 protein expression levels in HCT116 and LoVo cells compared with the control group. The intracellular reactive oxygen species (ROS) measurement results also indicated that compared with the control group, lycorine significantly induced ROS accumulation, and increased phosphorylated-p38 expression levels and AKT phosphorylation. Collectively, the present study suggested that lycorine might induce cell cycle arrest and exert cytostatic effects potentially via activating ROS/p38 and AKT signaling pathways in CRC cells.
Complete mitochondrial genome of Penthimia melanocephala Motschulsky, 1863 (Hemiptera: Cicadellidae: Deltocephalinae)

Abstract Penthimia is the largest genus in the tribe Penthimiini of the subfamily Deltocephalinae. To date, there are no available mitogenome sequences from Penthimia. In this study, we have sequenced and annotated the complete mitogenome of Penthimia melanocephala (Motschulsky 1863), the mitogenome is 15,308 bp in length, which including 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), 22 transfer RNAs (tRNAs) and a long non-coding region (control Region), base composition of whole sequences are A (50.4%), C (15.3%), G (10.0%), and T (24.3%). All PCGs started with the typical ATN codon and stopped with the typical TAN codon except for COII and COIII stopped with single T. Within phylogenetic tree, Deltocephalinae members were clustered into a clade. The complete mitogenome of P. melanocephala can provide essential DNA molecular data for further evolutionary and phylogenetic analysis.
The Diagnostic Value of Serum PIVKA-II Alone or in Combination with AFP in Chinese Hepatocellular Carcinoma Patients

Background At present, the diagnostic accuracy of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is insufficient. It remains controversial whether prothrombin induced by vitamin K absence II (PIVKA-II) has a better diagnostic value than AFP for HCC patients. Objective To investigate the diagnostic role of PIVKA-II alone or in combination with AFP in Chinese HCC patients. Methods Serum AFP and PIVKA-II levels were detected and analyzed in 308 HCC afflicted patients and 120 unafflicted controls. The receiver operator curve (ROC) and area under the curve (AUC) were conducted to evaluate the clinical value of AFP and PIVKA-II for diagnosing HCC and early HCC. Results In the whole HCC cohort, the diagnostic values of PIVKA-II were better than that of AFP. The AUC of PIVKA-II and AFP was 0.90 (95% CI 0.87-0.94) and 0.79 (95% CI 0.74-0.84), respectively. “AFP + PIVKA-II” yielded a high sensitivity of 95.1% and a specificity of 83.3%, with the AUC 0.89 (95% CI 0.85-0.93). In the early stage HCC group, the diagnostic accuracy of PIVKA-II was also better than that of AFP. The AUC of PIVKA-II and AFP was 0.83 (95% CI 0.77-0.89) and 0.75 (95% CI 0.68-0.81), respectively. “AFP + PIVKA-II” achieved the sensitivity of 83.3% and specificity of 89.1%, with an AUC of 0.86 (95% CI 0.81-0.91). Moreover, for AFP-negative HCC patients, serum PIVKA-II showed good diagnostic performance, with an AUC of 0.804 (95% CI 0.720-0.887). Besides, elevated PIVKA-II level was a strong independent risk factor for HCC patients with portal vein tumor thrombus (PVTT) (OR = 4.890, P = 0.020). Conclusion PIVKA-II is superior to AFP in HCC screening, and AFP in combination with PIVKA-II significantly improves the diagnostic value for Chinese HCC patients. PIVKA-II could effectively indicate HCC accompanied by PVTT and help to optimize the therapeutic strategy.
The Protective Effects of Maresin 1 in the OVA-Induced Asthma Mouse Model

Asthma is a chronic inflammatory disease that cannot be cured. Maresin 1 (MaR1) is a specific lipid synthesized by macrophages that exhibits powerful anti-inflammatory effects in various inflammatory diseases. The goal of this study was to evaluate the effect of MaR1 on allergic asthma using an ovalbumin- (OVA-) induced asthma model. Thirty BALB/c mice were randomly allocated to control, OVA, and MaR1 + OVA groups. Mice were sacrificed 24 hours after the end of the last challenge, and serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected for further analysis. Western blotting was used to measure the protein level of IκBα, the activation of the NF-κB signaling pathway, and the expression of NF-κB downstream inflammatory cytokines. Quantitative real-time polymerase chain reactions (qRT-PCRs) were used to evaluate the expression levels of COX-2 and ICAM-1 in lung tissues. We found that high doses of MaR1 were most effective in preventing OVA-induced inflammatory cell infiltration and excessive mucus production in lung tissue, reducing the number of inflammatory cells in the BALF and inhibiting the expression of serum or BALF-associated inflammatory factors. Furthermore, high-dose MaR1 treatment markedly suppressed the activation of the NF-κB signaling pathway, the degradation of IκBα, and the expression of inflammatory genes downstream of NF-κB, such as COX-2 and ICAM-1, in the OVA-induced asthma mouse model. Our findings indicate that MaR1 may play a critical role in OVA-induced asthma and may be therapeutically useful for the management of asthma.
Phenotypic profiling and prognostic significance of immune infiltrates in esophageal squamous cell carcinoma

ABSTRACT The tumor microenvironment (TME) of esophageal squamous cell carcinoma (ESCC) impacts tumor progression but is poorly understood. We obtained tumor tissues from 279 patients after esophagectomy and characterized the TME in intraepithelial and stromal regions using multiplex fluorescent immunohistochemistry (mfIHC). A heterogeneous immune population infiltrating tumor and the uninvolved esophageal tissue were observed. The infiltration of intraepithelial programmed death ligand 1 (PD-L1)-positive tumor-associated macrophages (TAMs) and stromal granzyme B+ activated cytotoxic T cells (aCTLs) correlated with both prolonged overall survival (OS) and disease-free survival (DFS). The intraepithelial memory T cell infiltration predicted longer OS, while intraepithelial and stromal regulatory T cell (Treg) infiltration was associated with shortened OS and DFS, respectively. Multivariate models combining immune infiltrates and clinicopathological factors outperformed tumor-node-metastasis (TNM) stage in predicting OS and DFS at 3 and 5 years. The infiltration of Treg inversely correlated with that of the antitumor effectors including CTLs, aCTLs, and natural killer (NK) cells. Intraepithelial memory T cell infiltration also negatively correlated with PD-L1 expression. In spatial analysis, intraepithelial dendritic cell (DC)-memory T cell engagement increased in high PD-L1+ TAM infiltration group. The characterization of the TME revealed a complex interplay between immune populations and may be employed to stratify patient for prognosis prediction and immunotherapy.
Nerve biopsy: Current indications and decision tools

After initial investigation of patients presenting with symptoms suggestive of neuropathy, a clinical decision is made for a minority of patients to undergo further assessment with nerve biopsy. Many nerve biopsies do not demonstrate a definitive pathological diagnosis and there is considerable cost and morbidity associated with the procedure. This highlights the need for appropriate selection of patients, nerves and neuropathology techniques. Additionally, concomitant muscle and skin biopsies may improve the diagnostic yield in some cases. Several advances have been made in diagnostics in recent years, particularly in genomics. The indications for nerve biopsy have consequently changed over time. This review explores the current indications for nerve biopsies and some of the issues surrounding its use. Also included are comments on alternative diagnostic modalities that may help to supplant or reduce the use of nerve biopsy as a diagnostic test. These primarily include extraneural biopsy and neuroimaging techniques such as magnetic resonance neurography and nerve ultrasound. Finally, we propose an algorithm to assist in deciding when to perform nerve biopsies.
Growth and adhesion inhibition of pathogenic bacteria by live and heat-killed food-origin Lactobacillus strains or their supernatants.

The study aimed to evaluate qualitatively and quantitatively the antimicrobial capacity of ten potential probiotic Lactobacillus strains against model enteropathogens and spoilage microorganisms. The probiotic strains (live and heat-killed forms) were also assessed for their ability to inhibit adhesion of selected pathogens to Caco-2 cells. The largest inhibition zones (the diffusion method) were connected with the usage of whole bacteria cultures (WBC), also high and moderate with cell free supernatant (CFS), and the lowest with cell free neutralized supernatant (CNS). The highest antagonistic activity of Lactobacillus strains was observed against L. monocytogenes strains, moderate activity against Salmonella, Shigella, E. coli, Pseudomonas and, the lowest against S.aureus, Bacillus, and Enterococcus. The inhibition of adhesion to Caco-2 cells was very high in the case of E. coli, Salmonella, and L. monocytogenes, and moderate in the case of S.aureus. On average, the inhibition effect was higher when pathogenic bacteria were treated by WBC, than heat-killed Lactobacillus. Although, in most samples, the effect was not significantly different (p>0.05). The strains Lb. brevis O24 and Lb. rhamnosus K3 showed the biggest overall antimicrobial properties, and were most effective in adherence inhibition of investigated indicator strains. These bacteria or their metabolites can be used for the production of various foods or pharmaceutical products.
Weighted Lotteries and the Allocation of Scarce Medications for Covid‐19

Abstract The allocation of vaccines and therapeutics for Covid‐19 obviously raises ethical questions, and physicians and ethicists have begun to address them. Writers have identified various criteria that should guide allocation decisions, but the criteria often conflict and need to be balanced against one another. This article proposes a model for thinking about how different considerations that are relevant to the distribution of vaccines and scarce treatments for Covid‐19 could be integrated into an allocation procedure. The model employs the construct of a weighted lottery, which is a construct that has been employed in other contexts that involve the distribution of scarce resources. The article highlights the advantages of applying a weighted lottery to the Covid‐19 context and offers an illustration for how it might work in practice. The primary aim of the article is to articulate the structural features of a weighted lottery for this context and to bring out its advantages over other methods for allocating Covid‐19 medications.
Noninvasive evaluation of intragraft immune responses in upper extremity transplantation

In vascularized composite allotransplantation (VCA), invasive tissue biopsies remain the gold standard in diagnosing rejection carrying significant morbidity. We aimed to show feasibility of tape‐stripping for noninvasive immune monitoring in VCA. Tape‐stripping was performed on allografts and native skin of upper extremity transplant recipients. Healthy nontransplanted individuals served as controls. The technique was also used in swine on naïve skin in nontransplanted animals, native skin of treated, transplanted swine, nonrejecting VCAs, and rejecting VCAs. Extracted protein was analyzed for differences in cytokine expression using Luminex technology. Significantly decreased levels of INFγ and IL‐1Ra were seen between human allograft samples and native skin. In swine, rejecting grafts had increased IL‐1Ra compared to naïve and native skin, decreased levels of GM‐CSF compared to native skin, and decreased IL‐10 compared to nonrejecting grafts. Unsupervised hierarchical clustering revealed rejecting grafts separated from the nonrejecting (P = 0.021). Variable importance in projection scores identified GM‐CSF, IL‐1Ra, and IL‐2 as the most important profiles for group discrimination. Differences in cytokine expression are detectable in human VCA patient native skin and VCA graft skin using a noninvasive tape‐stripping method. Swine studies suggest that differences in cytokines between rejecting and nonrejecting grafts are discernable.
BLOC1S1/GCN5L1/BORCS1 is a critical mediator for the initiation of autolysosomal tubulation

ABSTRACT The mechanisms orchestrating recycling of lysosomes through autophagic lysosome reformation (ALR) is incompletely understood. Previous data show that genetic depletion of BLOC1S1/GCN5L1/BORCS1 increases autolysosome (AL) accumulation. We postulated that this phenotype may manifest due to perturbed ALR. We explored this in control and bloc1s1 liver-specific knockout (LKO) mouse hepatocytes, showing that in response to nutrient-deprivation LKO’s fail to initiate ALR due to blunted lysosomal tubulation. As kinesin motor proteins and the intracellular cytoskeleton are requirements for tubular formation from ALs, we explored the interaction of BLOC1S1 with motor proteins and cytoskeletal factors. BLOC1S1 interacts with the ARL8B-KIF5B (GTPase and kinesin motor protein) complex to recruit KIF5B to ALs. Furthermore, BLOC1S1 interacts with the actin nucleation promoting factor WHAMM, which is an essential structural protein in the initiation of lysosomal tubulation (LT). Interestingly, the genetic reintroduction of BLOC1S1 rescues LT in LKO hepatocytes, but not when KIF5B is concurrently depleted. Finally, given the central role of MTORC1 signaling in ALR initiation, it was interesting that MTORC1 activity was increased despite the absence of LT in LKO hepatocytes. Concurrently, inhibition of MTORC1 abolished BLOC1S1 reconstitution-mediated rescue of LT in LKO hepatocytes. Taken together these data demonstrate that the functional interaction of BLOC1S1 with the kinesin binding complex and the actin cytoskeleton are a requirement for LT which, in parallel with MTORC1 signaling, initiate lysosome recycling via ALR. Abbreviations: 3-MA: 3-methyladenine; AL: autolysosome; ALR: autophagic lysosome reformation; ARL8B: ADP-ribosylation factor-like protein 8B; ARPC2: actin related protein 2/3 complex, subunit 2; ATAT1/αTAT1: alpha tubulin acetyltransferase 1; AVd: autophagic vacuoles, degradative; BLOC1S1/GCN5L1: biogenesis of lysosomal organelles complex-1, subunit 1; CQ: chloroquine; KIF5B: kinesin family member 5B; KLC1: kinesin light chain 1; LAMP1: lysosomal-associated membrane protein 1; LAMP2: lysosomal-associated membrane protein 2; LC3B-I: cytosolic form of LC3B; LC3B-II: lipidated form of LC3B; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; LKO: liver-specific knockout; LIs: lysosome inhibitors; LT: lysosomal tubulation; Ly: lysosome; MTORC1: mechanistic target of rapamycin kinase complex 1; PLEKHM2/SKIP: pleckstrin homology domain containing, family M (with RUN domain) member 2; Snapin: SNAP-associated protein; SQSTM1/p62: sequestosome 1; SVPs: synaptic vesicle precursors; TFEB: transcription Factor EB; TFE3: transcription factor E3; WHAMM: WAS protein homolog associated with actin, golgi membranes and microtubules.
Coping strategies: Seeking personalized care in relapsing-remitting multiple sclerosis. A patient reported measure–coping responses inventory

Background Coping is defined as a set of cognitive and behavioral efforts made to master stressful specific demands. Adaptation to chronic diseases, such as Multiple Sclerosis (MS), depends on the effectiveness of coping. Objective: To assess the psychometric properties of the Coping Responses Inventory (CRI-A) in persons with MS (PwMS), verifying the transferability of the measure, already validated in the Argentine general population, and to describe the types of coping strategies available for PwMS. Methods: 90 PwMS were included. Outcome measures: CRI-A Inventory, Expanded Disability Status Scale (EDSS), Beck Depression Inventory, Fatigue Severity Scale and MS International Quality of Life questionnaire. Results: Descriptive data is as follows: mean age (years): 40.97 ± 12.85; years of education: 13.46 ± 3.93; EDSS: 2.48 ± 1.79; disease evolution (years): 10.76 ± 9.72; depression: 13.92 ± 10.45; fatigue 3.77 ± 1.72. The psychometric properties of the CRI-A Inventory observed in the Argentine general population are present in the MS sample as well, with adequate validity and reliability. The respondents most frequently utilized a problem-focused coping style. Conclusions: Results showed the CRI-A has good transferability properties from the Argentine general population to the MS population.