bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychometric properties of the 12-item WHODAS applied through phone survey: an experience in PERSIAN Traffic Cohort
Authors: Shahedifar Nasrin , Sadeghi-Bazargani Homayoun , Asghari-Jafarabadi Mohammad , Farahbakhsh Mostafa , Bazargan-Hejazi Shahrzad 
Published: July 2022

AbstractBackgroundDue to limited capability to function in post-injury daily life injury, survivors need to be reliably assessed without need to commute more than necessary. The key action is to determine the level of functioning difficulties. Having the opportunity of conducting a national post-crash traffic safety and health cohort study, we aimed to translate into Persian and assess the psychometric properties of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) through phone surveys six month post injury.MethodsFirst, having World Health Organization permission, we tested the translation validity by forward translation, expert panel evaluation, back-translation, pre-testing and cognitive interviewing, and finalizing the Persian WHODAS. Then, through a psychometric study within a national cohort platform, the validity, reliability and applicability of the 12-item WHODAS was assessed through phone surveys. We included data of 255 road traffic injury patients enrolled from the cohort at six-month follow-up. The psychometric assessment (internal consistency reliability and stability reliability) was conducted on test–retest data of 50 patients with an average 7-day time span. An exploratory factor analysis tested the construct validity using extraction method of principal component factor and oblique rotation on data from 255 patients. Regarding the multiple criteria including an eigenvalue > 0.9, Cattell’s scree test, cumulative variance, and the theoretical basis, the minimum number of factors were retained. Data were analyzed using STATA statistical software package.ResultsThe respondents were mostly male (81%), employed (71%), educated (87%), and with a mean age of 37.7(14.9). The Persian version had high internal consistency reliability (Cronbach’s α = 0.93) and excellent stability reliability (ICC = 0.97, 95% CI: 0.92–0.98). An exploratory factor analysis retained four factors defining 86% of all the variance. Factors of Self-care, Mobility, and Cognition were completely retained.ConclusionsThe brief Pesrian WHODAS 2.0 was highly reliable and valid to be applied through phone interviews post injury.
The efficient circulating immunoscore predicts prognosis of patients with advanced gastrointestinal cancer
Authors: Zhao Yamei , Tang Yan , Qin Hanlin , Feng Kehai , Hu Changlu 
Published: July 2022

Abstract
Background
Immunoscore from tumor tissues was initially established to evaluate the prognosis of solid tumor patients. However, the feasibility of circulating immune score (cIS) for the prognosis of advanced gastrointestinal cancers (AGC) has not been reported.

Material and methods
Peripheral venous blood was collected from 64 untreated AGC patients. We utilized flow cytometry to determine several immune cell subpopulations, including CD8+ and CD4+ T cells, NK cells, and CD4 + CD25 + CD127low Tregs. The circulating immune score 1 (cIS1) was assessed according to the proportions of CD4+, CD8+ T cells, and NK cell, whereas circulating immune score 2 (cIS2) was derived from the proportions of CD4+, CD8+ T cell, and CD4 + CD25 + CD127low Tregs. The prognostic role of cIS for progression-free survival (PFS) and overall survival (OS) was analyzed using Kaplan–Meier curves and Cox multivariate models. Receiver operating characteristic (ROC) curves were depicted to compare the prognostic values of cIS1 and cIS2.

Results
AGC patients with high cIS1(≥ 2) and cIS2(≥ 2) had significantly longer PFS (cIS1: median PFS, 11 vs. 6.7 months, P = 0.001; cIS2: 12 vs. 5.8 months, P < 0.0001) and OS (cIS1: median OS, 12 vs. 7.9 months, P = 0.0004; cIS2: 12.8 vs. 7.4 months, P < 0.0001) than those with low cIS1 and low cIS2. The areas under ROC curves (AUROCs) of cIS1 and cIS2 for OS were 0.526 (95% confidence interval; 95% CI 0.326–0.726) and 0.603 (95% CI 0.427–0.779, P = 0.332), whereas AUROC of cIS2 for PFS was larger than that of cIS1 0.735 (95% CI 0.609–0.837) vs 0.625 (95% CI 0.495–0.743) (P = 0.04)).

Conclusion
The cIS can be applied to predict the prognosis of untreated AGC patients. Compared with cIS1, cIS2 displayed superior prognostic value for PFS prediction.
Modulation of C5a–C5aR1 signaling alters the dynamics of AD progression
Authors: Carvalho Klebea , Schartz Nicole D. , Balderrama-Gutierrez Gabriela , Liang Heidi Y. , Chu Shu-Hui , Selvan Purnika , Gomez-Arboledas Angela , Petrisko Tiffany J. , Fonseca Maria I. , Mortazavi Ali , Tenner Andrea J. 
Published: July 2022

Abstract
Background
The complement system is part of the innate immune system that clears pathogens and cellular debris. In the healthy brain, complement influences neurodevelopment and neurogenesis, synaptic pruning, clearance of neuronal blebs, recruitment of phagocytes, and protects from pathogens. However, excessive downstream complement activation that leads to generation of C5a, and C5a engagement with its receptor C5aR1, instigates a feed-forward loop of inflammation, injury, and neuronal death, making C5aR1 a potential therapeutic target for neuroinflammatory disorders. C5aR1 ablation in the Arctic (Arc) model of Alzheimer’s disease protects against cognitive decline and neuronal injury without altering amyloid plaque accumulation.

Methods
To elucidate the effects of C5a–C5aR1 signaling on AD pathology, we crossed Arc mice with a C5a-overexpressing mouse (ArcC5a+) and tested hippocampal memory. RNA-seq was performed on hippocampus and cortex from Arc, ArcC5aR1KO, and ArcC5a+ mice at 2.7–10 months and age-matched controls to assess mechanisms involved in each system. Immunohistochemistry was used to probe for protein markers of microglia and astrocytes activation states.

Results
ArcC5a+ mice had accelerated cognitive decline compared to Arc. Deletion of C5ar1 delayed or prevented the expression of some, but not all, AD-associated genes in the hippocampus and a subset of pan-reactive and A1 reactive astrocyte genes, indicating a separation between genes induced by amyloid plaques alone and those influenced by C5a–C5aR1 signaling. Biological processes associated with AD and AD mouse models, including inflammatory signaling, microglial cell activation, and astrocyte migration, were delayed in the ArcC5aR1KO hippocampus. Interestingly, C5a overexpression also delayed the increase of some AD-, complement-, and astrocyte-associated genes, suggesting the possible involvement of neuroprotective C5aR2. However, these pathways were enhanced in older ArcC5a+ mice compared to Arc. Immunohistochemistry confirmed that C5a–C5aR1 modulation in Arc mice delayed the increase in CD11c-positive microglia, while not affecting other pan-reactive microglial or astrocyte markers.

Conclusion
C5a–C5aR1 signaling in AD largely exerts its effects by enhancing microglial activation pathways that accelerate disease progression. While C5a may have neuroprotective effects via C5aR2, engagement of C5a with C5aR1 is detrimental in AD models. These data support specific pharmacological inhibition of C5aR1 as a potential therapeutic strategy to treat AD.
Glioblastoma disrupts the ependymal wall and extracellular matrix structures of the subventricular zone
Authors: Norton Emily S. , Whaley Lauren A. , Ulloa-Navas María José , García-Tárraga Patricia , Meneses Kayleah M. , Lara-Velazquez Montserrat , Zarco Natanael , Carrano Anna , Quiñones-Hinojosa Alfredo , García-Verdugo José Manuel , Guerrero-Cázares Hugo 
Published: July 2022

Abstract
Background
Glioblastoma (GBM) is the most aggressive and common type of primary brain tumor in adults. Tumor location plays a role in patient prognosis, with tumors proximal to the lateral ventricles (LVs) presenting with worse overall survival, increased expression of stem cell genes, and increased incidence of distal tumor recurrence. This may be due in part to interaction of GBM with factors of the subventricular zone (SVZ), including those contained within the cerebrospinal fluid (CSF). However, direct interaction of GBM tumors with CSF has not been proved and would be hindered in the presence of an intact ependymal cell layer.

Methods
Here, we investigate the ependymal cell barrier and its derived extracellular matrix (ECM) fractones in the vicinity of a GBM tumor. Patient-derived GBM cells were orthotopically implanted into immunosuppressed athymic mice in locations distal and proximal to the LV. A PBS vehicle injection in the proximal location was included as a control. At four weeks post-xenograft, brain tissue was examined for alterations in ependymal cell health via immunohistochemistry, scanning electron microscopy, and transmission electron microscopy.

Results
We identified local invading GBM cells within the LV wall and increased influx of CSF into the LV-proximal GBM tumor bulk compared to controls. In addition to the physical disruption of the ependymal cell barrier, we also identified increased signs of compromised ependymal cell health in LV-proximal tumor-bearing mice. These signs include increased accumulation of lipid droplets, decreased cilia length and number, and decreased expression of cell channel proteins. We additionally identified elevated numbers of small fractones in the SVZ within this group, suggesting increased indirect CSF-contained molecule signaling to tumor cells.

Conclusions
Our data is the first to show that LV-proximal GBMs physically disrupt the ependymal cell barrier in animal models, resulting in disruptions in ependymal cell biology and increased CSF interaction with the tumor bulk. These findings point to ependymal cell health and CSF-contained molecules as potential axes for therapeutic targeting in the treatment of GBM.
Binning long reads in metagenomics datasets using composition and coverage information
Authors: Wickramarachchi Anuradha , Lin Yu 
Published: July 2022

AbstractBackgroundAdvancements in metagenomics sequencing allow the study of microbial communities directly from their environments. Metagenomics binning is a key step in the species characterisation of microbial communities. Next-generation sequencing reads are usually assembled into contigs for metagenomics binning mainly due to the limited information within short reads. Third-generation sequencing provides much longer reads that have lengths similar to the contigs assembled from short reads. However, existing contig-binning tools cannot be directly applied on long reads due to the absence of coverage information and the presence of high error rates. The few existing long-read binning tools either use only composition or use composition and coverage information separately. This may ignore bins that correspond to low-abundance species or erroneously split bins that correspond to species with non-uniform coverages. Here we present a reference-free binning approach, LRBinner, that combines composition and coverage information of complete long-read datasets. LRBinner also uses a distance-histogram-based clustering algorithm to extract clusters with varying sizes.ResultsThe experimental results on both simulated and real datasets show that LRBinner achieves the best binning accuracy in most cases while handling the complete datasets without any sampling. Moreover, we show that binning reads using LRBinner prior to assembly reduces computational resources required for assembly while attaining satisfactory assembly qualities.ConclusionLRBinner shows that deep-learning techniques can be used for effective feature aggregation to support the metagenomics binning of long reads. Furthermore, accurate binning of long reads supports improvements in metagenomics assembly, especially in complex datasets. Binning also helps to reduce the resources required for assembly. Source code for LRBinner is freely available at https://github.com/anuradhawick/LRBinner.
DUB1 suppresses Hippo signaling by modulating TAZ protein expression in gastric cancer
Authors: Wang Dehai , Li Zhongbo , Li Xin , Yan Cheng , Yang Huijie , Zhuang Ting , Wang Xiao , Zang Yifeng , Liu Ziping , Wang Tianshi , Jiang Rixia , Su Peng , Zhu Jian , Ding Yinlu 
Published: July 2022

AbstractBackgroundThe Hippo pathway functions as a tumor suppressor pathway in human cancers, while dysfunction of the Hippo pathway is frequently observed in malignancies. Although YAP/TAZ activity is tightly controlled by the phosphorylation cascade of the MST-LATS-YAP/TAZ axis, it is still unclear why the YAP/TAZ proteins are activated in human cancers despite Hippo pathway activation. Recent studies have suggested that in addition to phosphorylation, several other posttranslational modifications, including ubiquitination, also play critical roles in modulating TAZ function.MethodsWe used several gastric cancer cell lines and performed western blot analysis, real-time PCR, immunoprecipitation assays, and in vitro ubiquitination assays and established a xenograft mouse model.ResultsHere, by screening a DUB (deubiquitinase) siRNA library, we discovered that DUB1 functions as a critical modulator that facilitates gastric cancer stemness and progression by deubiquitinating and activating the TAZ protein. We also found that DUB1 expression was elevated in gastric cancer and that elevated DUB1 expression correlated with TAZ activation and poor survival. DUB1 associates with the TAZ protein and deubiquitinates TAZ at several lysine residues, which subsequently stabilizes TAZ and facilitates its function.ConclusionsOur study revealed a novel deubiquitinase in the Hippo/TAZ axis and identified one possible therapeutic target for Hippo-driven gastric cancer.
Emerging roles of circular RNAs in gastric cancer metastasis and drug resistance
Authors: Wang Xiaolin , Zhang Jiahui , Cao Guozhen , Hua Jinghan , Shan Ge , Lin Wenchu 
Published: July 2022

AbstractGastric cancer (GC) is an aggressive malignancy with a high mortality rate and poor prognosis, primarily caused by metastatic lesions. Improved understanding of GC metastasis at the molecular level yields meaningful insights into potential biomarkers and therapeutic targets. Covalently closed circular RNAs (circRNAs) have emerged as crucial regulators in diverse human cancers including GC. Furthermore, accumulating evidence has demonstrated that circRNAs exhibit the dysregulated patterns in GC and have emerged as crucial regulators in GC invasion and metastasis. However, systematic knowledge regarding the involvement of circRNAs in metastatic GC remains obscure. In this review, we outline the functional circRNAs related to GC metastasis and drug resistance and discuss their underlying mechanisms, providing a comprehensive delineation of circRNA functions on metastatic GC and shedding new light on future therapeutic interventions for GC metastases.
New solid phase methodology for the synthesis of biscoumarin derivatives: experimental and in silico approaches
Authors: Zarenezhad Elham , Montazer Mohammad Nazari , Tabatabaee Masoumeh , Irajie Cambyz , Iraji Aida 
Published: July 2022

AbstractThe simple and greener one-pot approach for the synthesis of biscoumarin derivatives using catalytic amounts of nano-MoO3catalyst under mortar-pestle grinding was described. The use of non-toxic and mild catalyst, cost-effectiveness, ordinary grinding, and good to the excellent yield of the final product makes this procedure a more attractive pathway for the synthesis of biologically remarkable pharmacophores. Accordingly, biscoumarin derivatives were successfully extended in the developed protocols.Next, a computational investigation was performed to identify the potential biological targets of this set of compounds. In this case, first, a similarity search on different virtual libraries was performed to find an ideal biological target for these derivatives. Results showed that the synthesized derivatives can be α-glucosidase inhibitors. In another step, molecular docking studies were carried out against human lysosomal acid-alpha-glucosidase (PDB ID: 5NN8) to determine the detailed binding modes and critical interactions with the proposed target. In silico assessments showed the gold score value in the range of 17.56 to 29.49. Additionally, molecular dynamic simulations and the MM-GBSA method of the most active derivative against α-glucosidase were conducted to study the behavior of selected compounds in the biological system. Ligand 1 stabilized after around 30 ns and participated in various interactions with Trp481, Asp518, Asp616, His674, Phe649, and Leu677 residues.
The IMD and Toll canonical immune pathways of Triatoma pallidipennis are preferentially activated by Gram-negative and Gram-positive bacteria, respectively, but cross-activation also occurs
Authors: Alejandro Alvarado-Delgado , Lilia Juárez-Palma , Jesús Maritinez-Bartneche , Henry Rodriguez Mario 
Published: July 2022

Abstract
Background
Antimicrobial peptides (AMPs) participate in the humoral immune response of insects eliminating invasive microorganisms. The immune deficiency pathway (IMD) and Toll are the main pathways by which the synthesis of these molecules is regulated in response to Gram-negative (IMD pathway) or Gram-positive (Toll pathway) bacteria. Various pattern-recognition receptors (PRRs) participate in the recognition of microorganisms, such as pgrp-lc and toll, which trigger signaling cascades and activate NF-κB family transcription factors, such as relish, that translocate to the cell nucleus, mainly in the fat body, inducing AMP gene transcription.

Methods
T. pallidipennis inhibited in Tppgrp-lc, Tptoll, and Tprelish were challenged with E. coli and M. luteus to analyze the expression of AMPs transcripts in the fat body and to execute survival assays.

Results
In this work we investigated the participation of the pgrp-lc and toll receptor genes and the relish transcription factor (designated as Tppgrp-lc, Tptoll, and Tprelish), in the transcriptional regulation of defensin B, prolixicin, and lysozyme B in Triatoma pallidipennis, one of the main vectors of Chagas disease. AMP transcript abundance was higher in the fat body of blood-fed than non-fed bugs. Challenge with Escherichia coli or Micrococcus luteus induced differential increases in AMP transcripts. Additionally, silencing of Tppgrp-lc, Tptoll, and Tprelish resulted in reduced AMP transcription and survival of bugs after a bacterial challenge.

Conclusions
Our findings demonstrated that the IMD and Toll pathways in T. pallidipennis preferentially respond to Gram-negative and Gram-positive bacteria, respectively, by increasing the expression of AMP transcripts, but cross-induction also occurs.

Graphical Abstract
Cannabinoid extract in microdoses ameliorates mnemonic and nonmnemonic Alzheimer’s disease symptoms: a case report
Authors: Ruver-Martins Ana Carolina , Bicca Maíra Assunção , de Araujo Fabiano Soares , de Noronha Sales Maia Beatriz Helena Lameiro , Pamplona Fabrício Alano , da Silva Elton Gomes , Nascimento Francisney Pinto 
Published: July 2022

Abstract
Background
Cannabinoid-based therapy has been shown to be promising and is emerging as crucial for the treatment of cognitive deficits, mental illnesses, and many diseases considered incurable. There is a need to find an appropriate therapy for Alzheimer’s disease, and cannabinoid-based therapy appears to be a feasible possibility.

Case presentation
This report addresses the beneficial effect of cannabinoids in microdoses on improving memory and brain functions of a patient with mild-stage Alzheimer’s disease. The patient is a 75-year-old white man presenting with main symptoms of memory deficit, spatial and temporal disorientation, and limited daily activity. The experimental therapeutic intervention was carried out for 22 months with microdoses of a cannabis extract containing cannabinoids. Clinical evaluations using Mini-Mental State Examination and Alzheimer’s Disease Assessment Scale-Cognitive Subscale were performed.

Conclusions
Here we provide original evidence that cannabinoid microdosing could be effective as an Alzheimer’s disease treatment while preventing major side effects. This is an important step toward dissociating cannabinoids’ health-improving effects from potential narcotic-related limitations.
Transjugular intrahepatic portosystemic shunt, local thrombaspiration, and lysis for management of fulminant portomesenteric thrombosis and atraumatic splenic rupture due to vector-vaccine-induced thrombotic thrombocytopenia: a case report
Authors: Stoll Sandra Emily , Werner Patrick , Wetsch Wolfgang A. , Dusse Fabian , Bunck Alexander C. , Kochanek Matthias , Popp Felix , Schmidt Thomas , Bruns Christiane , Böttiger Bernd W. 
Published: July 2022

AbstractIntroductionRecombinant adenoviral vector vaccines against severe acute respiratory syndrome coronavirus 2 have been observed to be associated with vaccine-induced immune thrombotic thrombocytopenia. Though vaccine-induced immune thrombotic thrombocytopenia is a rare complication after vaccination with recombinant adenoviral vector vaccines, it can lead to severe complications. In vaccine-induced immune thrombotic thrombocytopenia, the vector vaccine induces heparin-independent production of platelet factor 4 autoantibodies, resulting in platelet activation and aggregation. Therefore, patients suffering from vaccine-induced immune thrombotic thrombocytopenia particularly present with signs of arterial or venous thrombosis, often at atypical sites, but also signs of bleeding due to disseminated intravascular coagulation and severe thrombocytopenia. We describe herein a rare case of fulminant portomesenteric thrombosis and atraumatic splenic rupture due to vaccine-induced immune thrombotic thrombocytopenia.Case summary (main symptoms and therapeutic interventions)This case report presents the diagnosis and treatment of a healthy 29-year-old male Caucasian patient suffering from an extended portomesenteric thrombosis associated with atraumatic splenic rupture due to vaccine-induced immune thrombotic thrombocytopenia after the first dose of an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 [ChAdOx1 nCoV-19 (AZD1222)]. Therapeutic management of vaccine-induced immune thrombotic thrombocytopenia initially focused on systemic anticoagulation avoiding heparin and the application of steroids and intravenous immune globulins as per the recommendations of international societies of hematology and hemostaseology. Owing to the atraumatic splenic rupture and extended portomesenteric thrombosis, successful management of this case required splenectomy with additional placement of a transjugular intrahepatic portosystemic shunt to perform local thrombaspiration, plus repeated local lysis to reconstitute hepatopetal blood flow.ConclusionThe complexity and wide spectrum of the clinical picture in patients suffering from vaccine-induced immune thrombotic thrombocytopenia demand an early interdisciplinary diagnostic and therapeutic approach. Severe cases of portomesenteric thrombosis in vaccine-induced immune thrombotic thrombocytopenia, refractory to conservative management, may require additional placement of a transjugular intrahepatic portosystemic shunt, thrombaspiration, thrombolysis, and surgical intervention for effective management.