bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caprin-1 plays a role in cell proliferation and Warburg metabolism of esophageal carcinoma by regulating METTL3 and WTAP
Authors: Gao Yan , Yuan Lingling , Ke Changbin , Pei Zhijun , Liu Xiaobo , Wu Ruimin , Kui Xueyan , Zhang Yanmin 
Published: February 2023

Abstract
Background
Cytoplasmic activation/proliferation-associated protein-1 (Caprin-1) is implicated in cancer cell proliferation and tumorigenesis; however, its role in the development of esophageal carcinoma (ESCA) has not been examined.

Methods
Biological methods and data analysis were used to investigate the expression of Caprin-1 in ESCA tissue and cell lines. We comprehensively analyzed the mRNA expression and prognostic values, signalling pathways of CAPRIN1 in ESCA using public databases online. Biological functions of CAPRIN1 were performed by clorimetric growth assay, EdU staining, colony formation, flow cytometry, apoptosis analysis, Western blot, lactate detection assay, extracellular acidification rates. The underlying mechanism was determined via flow cytometric analysis, Western blot and rescue experiments. In addition, xenograft tumor model was constructed to verify the phenotypes upon CAPRIN1 silencing.

Results
Caprin-1 expression was significantly elevated in both ESCA tumor tissues and cell lines compared with that in normal adjacent tissues and fibroblasts. Increased CAPRIN1 mRNA expression was significantly associated with clinical prognosis and diagnostic accuracy. The GO enrichment and KEGG pathway analysis CAPRIN1 might be related to immune-related terms, protein binding processes, and metabolic pathways. A significant positive correlation was observed between high Caprin-1 protein levels and lymph node metastasis (P = 0.031), ki-67 (P = 0.023), and 18F- FDG PET/CT parameters (SUVmax (P = 0.002) and SUV mean (P = 0.005)) in 55 ESCA patients. At cut-off values of SUVmax 17.71 and SUVmean 10.14, 18F- FDG PET/CT imaging predicted Caprin-1 expression in ESCA samples with 70.8% sensitivity and 77.4% specificity. In vitro and in vivo assays showed that Caprin-1 knockdown affected ESCA tumor growth. Silencing Caprin-1 inhibited ESCA cell proliferation and glycolysis, and decreased the expression of methyltransferase-like 3 (METTL3) and Wilms’ tumor 1-associating protein (WTAP). However, this effect could be partially reversed by the restoration of METTL3 and WTAP expression.

Conclusions
Our data suggest that Caprin-1 could serve as a prognostic biomarker and has an oncogenic role in ESCA.
Nanoscale, antigen encounter-dependent, IL-12 delivery by CAR T cells plus PD-L1 blockade for cancer treatment
Authors: Yang Zhifen , Pietrobon Violena , Bobbin Maggie , Stefanson Ofir , Yang Jin , Goswami Angshumala , Alphson Bennett , Choi Hana , Magallanes Khristina , Cai Qi , Barrett David , Wang Bing , Qi Lei S. , Marincola Francesco M. 
Published: February 2023

Abstract
Background
Chimeric antigen receptor (CAR)-T cell therapies for the treatment of hematological malignancies experienced tremendous progress in the last decade. However, essential limitations need to be addressed to further improve efficacy and reduce toxicity to assure CAR-T cell persistence, trafficking to the tumor site, resistance to an hostile tumor microenvironment (TME), and containment of toxicity restricting production of powerful but potentially toxic bioproducts to the TME; the last could be achieved through contextual release upon tumor antigen encounter of factors capable of converting an immune suppressive TME into one conducive to immune rejection.

Methods
We created an HER2-targeting CAR-T (RB-312) using a clustered regularly interspaced short palindromic repeats (CRISPR) activation (CRISPRa) system, which induces the expression of the IL-12 heterodimer via conditional transcription of its two endogenous subunits p35 and p40. This circuit includes two lentiviral constructs. The first one (HER2-TEV) expresses an anti-human epidermal growth factor receptor 2 (HER2) CAR single chain variable fragment (scFv), with CD28 and CD3z co-stimulatory domains linked to the tobacco etch virus (TEV) protease and two single guide RNAs (sgRNA) targeting the interleukin (IL)-12A and IL12B transcription start site (TSS), respectively. The second construct (LdCV) encodes linker for activation of T cells (LAT) fused to nuclease-deactivated Streptococcus Pyogenes Cas9 (dCas9)-VP64-p65-Rta (VPR) via a TEV-cleavable sequence (TCS). Activation of the CAR brings HER2-TEV in close proximity to LdCV releasing dCas9 for nuclear localization. This conditional circuit leads to conditional and reversible induction of the IL-12/p70 heterodimer. RB-312 was compared in vitro to controls (cRB-312), lacking the IL-12 sgRNAs and conventional HER2 CAR (convCAR).

Results
The inducible CRISPRa system activated endogenous IL-12 expression resulting in enhanced secondary interferon (FN)-γ production, cytotoxicity, and CAR-T proliferation in vitro, prolonged in vivo persistence and greater suppression of HER2+ FaDu oropharyngeal cancer cell growth compared to the conventional CAR-T cell product. No systemic IL-12 was detected in the peripheral circulation. Moreover, the combination with programmed death ligand (PD-L1) blockade demonstrated robust synergistic effects.

Conclusions
RB-312, the first clinically relevant product incorporating a CRISPRa system with non-gene editing and reversible upregulation of endogenous gene expression that promotes CAR-T cells persistence and effectiveness against HER2-expressing tumors. The autocrine effects of reversible, nanoscale IL-12 production limits the risk of off-tumor leakage and systemic toxicity.
Perimenopausal Effects of Estradiol on Anhedonia and Psychosis Study (PEEPs): study protocol for a neural and molecular mechanistic clinical trial
Authors: Walsh Melissa J. M. , Gibson Kathryn , Hynd Megan , Eisenlohr-Moul Tory A. , Walsh Erin C. , Schiff Lauren , Jarskog Fred , Lalush David , Dichter Gabriel S. , Schiller Crystal E. 
Published: February 2023

Abstract
Background
The perimenopausal transition is accompanied by psychiatric symptoms in over 10% of women. Symptoms commonly include depressed mood and anhedonia and less commonly include psychosis. Psychiatric symptoms have been linked to the depletion and/or variability of circulating estradiol, and estradiol treatment reduces perimenopausal anhedonia and psychosis in some women. Estrogen fluctuations may disrupt function in the mesolimbic reward system in some women, leading to psychiatric symptoms like anhedonia or psychosis. The Perimenopausal Effects of Estradiol on Anhedonia and Psychosis Study (PEEPs) is a mechanistic clinical trial that aims to (1) identify relationships between perimenopausal-onset anhedonia and psychosis and neuromolecular markers of mesolimbic reward responses and (2) determine the extent to which estradiol treatment-induced changes in mesolimbic reward responses are associated with alleviation of perimenopausal onset anhedonia or psychosis.

Methods
This study will recruit 100 unmedicated women ages 44–55 in the late-stage perimenopausal transition, sampling across the range of mild-to-high anhedonia and absent-to-moderate psychosis symptoms. Patients will be randomized to receive either estradiol or placebo treatment for 3 weeks. Clinical outcome measures will include symptoms of anhedonia (measured with Snaith–Hamilton Pleasure Scale; SHAPS) and psychosis (measured with Brief Psychiatric Rating Scale; BPRS psychosis subscale) as well as neural markers of mesolimbic reward system functioning, including reward-related fMRI activation and PET-derived measure of striatal dopamine binding. Pre-treatment associations between (1) SHAPS/BPRS scores and (2) reward-related striatal dopamine binding/BOLD activation will be examined. Furthermore, longitudinal mixed models will be used to estimate (1) symptom and neuromolecular trajectories as a function of estradiol vs. placebo treatment and (2) how changes in reward-related striatal dopamine binding and BOLD activation predict variability in symptom trajectories in response to estradiol treatment.

Discussion
This clinical trial will be the first to characterize neural and molecular mechanisms by which estradiol treatment ameliorates anhedonia and psychosis symptoms during the perimenopausal transition, thus laying the groundwork for future biomarker research to predict susceptibility and prognosis and develop targeted treatments for perimenopausal psychiatric symptoms. Furthermore, in alignment with the National Institute for Mental Health Research Domain Criteria initiative, this trial will improve our understanding of a range of disorders characterized by anhedonia, psychosis, and reward system dysfunction.

Trial registration
ClinicalTrials.gov NCT05282277
Distant genetic variants of Anaplasma phagocytophilum from Ixodes ricinus attached to people
Authors: Lesiczka Paulina Maria , Hrazdilova Kristyna , Hönig Václav , Modrý David , Zurek Ludek 
Published: February 2023

Abstract
Background
Although the tick-borne pathogen Anaplasma phagocytophilum is currently described as a single species, studies using genetic markers can distinguish groups of variants associated with different hosts, pathogenicity, zoonotic potential and biotic and geographic niches. The objective of our study was to investigate the genetic diversity of A. phagocytophilum and Ixodes ricinus ticks attached to people.

Methods
In collaboration with a commercial diagnostic company, a total of 52 DNA samples were obtained from ticks that tested positive for A. phagocytophilum by quantitative PCR. The genetic profile of each sample was determined using the groEL and ankA genes. Identification of the tick species was confirmed by partial sequencing of the COI subunit and a portion of the TROSPA gene.

Results
All 52 ticks were identified as I. ricinus. Two protocols of nested PCR amplifying 1293- and 407-bp fragments of groEL of A. phagocytophilum yielded amplicons of the expected size for all 52 samples. Among all sequences, we identified 10 unique genetic variants of groEL belonging to ecotype I and ecotype II. The analysis targeting ankA was successful in 46 of 52 ticks. Among all sequences, we identified 21 unique genetic variants phylogenetically belonging to three clusters.

Conclusions
Our results indicate that ticks attached to people harbor distant genetic variants of A. phagocytophilum, some of which are not recognized as zoonotic. Further studies are needed to determine the risk of human infection by genetic variants other than those designated as zoonotic.

Graphical Abstract
Calculated and measured radiation dose for the low energy xoft axxent eBT X-ray source
Authors: Can Sümeyra , Atilla Özge , Karaçetin Didem 
Published: February 2023

Abstract
Purpose
In this study, it was aimed to evaluate the functionality to deliver different prescription dose except 20 Gy for the Xoft Axxent Ebt (electronic Brachytherapy) system and analyzing the system in terms of radiation dosimetry in water and 0.9% isotonic Sodium Chloride (NaCl) solution.

Materials and methods
In the Xoft Axxent eBT, different prescription dose in single fraction were calculated for different balloon applicator volumes based on source position and irradiation times. EBT-XD Gafchromic film was calibrated at 6MV photon energy. A balloon applicator filled with 0.9% isotonic NaCl solution was used to deliver a radiation dose of 20 Gy, 16 Gy, 10 Gy on the applicator surface. Then the balloon applicator was filled with water and the same measurements were repeated. Finally, the balloon applicator was irradiated by positioning it at different distances in the water phantom to simulate the isodose contour.

Results
At the time the balloon applicator was filled with water and 0,9% NaCl solution, the difference between the planned dose and the absorbed dose was ~ 2% vs. 15% for 30 cc, ~ 5% vs. 14% for 35 cc and ~ 3,5% vs. 10% for 40 cc respectively. Finally, the absorbed dose at a distance of 1 cm from the applicator surface was measured as 9.63 Gy.

Conclusion
In this study, it was showed that different prescription dose could be possible to deliver in the Xoft Axxent eBT system based on the standard plan. In addition, the absorbed dose was higher than the planned dose depending on the effective atomic number of NaCl solution comparing to water due to photoelectric effect in low energy photons. By measuring the dose distributions at different distances from the balloon applicator surface, the absorbed dose in tissue equivalent medium was determined and the isodose contours characteristics was simulated.
Psychometric properties of the arabic version of the positive/negative experiences of parents for school-aged students about online learning during COVID-19 pandemic assessment scale
Authors: Bajamal Eman , Anazi Samaa Al , Esheaba Ola , Hantira Neama 
Published: February 2023

Abstract
Background
The current literature examining the impact of online learning on parents and their children, specifically in the time of COVID-19 are still lacking in Saudi Arabia. Therefore, the aim of the study to evaluate the psychometric properties of the Arabic version of the positive/negative experiences of online learning during COVID-19 Pandemic Assessment Scale.

Methods
A cross-sectional study approved by a university institutional review board was conducted among 184 participants in 2021. The scale was translated from English into Arabic and culturally adapted as needed. The psychometric properties of the instruments, including face and content validity, and internal consistency were evaluated. Exploratory factor analysis (EFA) was conducted to cross-validate the factor structure. The Spearman’s Rho Correlation was used to assess convergent validity.

Results
Cronbach’s alpha were 0.890 and 0.892, respectively, indicating acceptable internal consistency. Item-total correlation coefficients ranged from 0.52 to 0.73 and 0.43 to 0.76, respectively. The EFA indicated a single-factor with a total% variance 52.89 for the positive experience items of the scale and 56.83 for the negative experience items of the scale.

Conclusion
The Arabic version of the the positive/negative experiences of online learning during COVID-19 Pandemic Assessment Scale is reliable and valid measure for assessing parents experiences among Arabic-speaking population.
Macrocell Corrosion Currents in Simulated Concrete Pore Solution and Reinforced Concrete
Authors: Lliso-Ferrando Josep Ramon , Gasch Isabel , Martínez-Ibernón Ana , Valcuende Manuel 
Published: February 2023

AbstractChloride-induced rebar corrosion is one of the main causes of damage in reinforced concrete structures (RCS). Chloride attacks lead to depassivation creating pits, which can imply major losses of sections. The current generated at these spots (microcell) is contributed by the current produced between corroded and uncorroded areas (macrocell). The influence of both currents has been deeply investigated based on solution studies, which do not actually represent the behaviour of concrete-embedded elements. The studies about macrocell currents in solution are interesting to analyse this phenomenon quickly and simply. However, they must not be interpreted as the reality of RCS because this requires studies using rebars embedded in concrete. The performed experimental plan verified this fact. In addition, another objective of this study was to analyse the influence of concrete’s electrical resistance and the limiting effect of the cathode/anode surface (Cs/As) ratio on macrocell currents in solution and in concrete. For this study, specimens manufactured using concretes with different properties were used: standard concrete (SC), high-performance concrete (HPC), very high-performance concrete (VHPC) and ultra-high performance-fibre reinforced concrete (UHPFRC). The conclusions show how the Cs/As ratio plays a key role in regulating macrocell current intensity, but what really governs this phenomenon is concrete resistivity because it regulates the participation of a bigger or smaller cathode surface. The influence of this parameter as a limiting factor of macrocell currents is fundamental, especially in high resistivity concretes like VHPC and UHPFRC.
Accidental retropharyngeal dissection extending close to the right common carotid artery during nasotracheal intubation: a case report
Authors: Okamoto Aki , Kawaraguchi Yoshitaka , Fujita Masahide , Goto Yasunobu , Shimokawa Mitsuru 
Published: February 2023

Abstract
Background
Retropharyngeal dissection is a possible complication during nasotracheal intubation. We report a case of a retropharyngeal dissection extending close to the right common carotid artery occurring while inserting a nasotracheal tube.

Case presentation
An 81-year-old woman, scheduled for laparoscopic and endoscopic cooperative surgery for a duodenal tumor under general anesthesia, sustained submucosal dissection of the retropharyngeal space during nasotracheal intubation. Postoperative computed tomography revealed retropharyngeal tissue injury extending close to the right common carotid artery. The patient was treated with prophylactic antibiotic therapy and discharged uneventfully on postoperative day 13.

Conclusions
Submucosal dissection of the retropharyngeal tissue during nasotracheal intubation has a potential risk of major cervical vessel injury. Therefore, when the tip of the tube cannot be visualized within the oropharynx, clinicians must proceed with caution regarding the expected depth of the tube.
Pathogenicity of entomopathogenic nematodes against the new invasive fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae)
Authors: Mohamed Hend O. , Shairra Souad A. 
Published: February 2023

Abstract
Background
Fall armyworm (FAW), Spodopterafrugiperda (J. E. Smith) (Lepidoptera: Noctuidae) is the new invasive pest of different economic crops, threatening the agricultural economy worldwide. Chemical insecticides are the main control management strategy applied by almost farmers. As the adverse effect of these chemicals on the environment and human health, improving alternative environmentally friendly control against this pest is urgently needed. In this response, the pathogenicity bioassays of 2 entomopathogenic nematode species (EPNs), Steinernemacarpocapsae (All) and Heterorhabditisindica (EGAZ2), on different FAW larval instars (2nd to 6th instars) were assessed under laboratory conditions.

Results
The results cleared that FAW larval mortality rate was varied significantly related to nematode species, post-exposure times and developmental instar stages. S.carpocapsae application was more virulent and effective against all tested instars larvae, registering 100% mortality after 48–72 h post-exposure at different nematode concentrations (150–2400 IJs). However, H.indica caused 100% mortality in early instars only after 96 h, but late instars required a longer time extending to 120–188 h at tested concentrations. In this context, 2nd and 3rd instars were highly susceptible to Heterorhabditis species infection. Lower nematode concentrations (150–300 IJs) caused moderate mortality 33.33–50%, respectively, in 5th and 6th full-developed larvae only. All recovery larvae post-infection died in the pupal stage or adult emerged with wing malformation.

Conclusion
The 2 EPN species were virulent against different FAW larval instars at different concentrations and exposure times. Thereby, they are recommended as biocontrol agents against this invasive pest, particularly S.carpocapsae after low-exposure time. This study provides essential information on EPNs, which will further help in the practical application of biological control against fall armyworm.
Foot and mouth disease in Ethiopia: a systematic review and meta-analysis in the last fifteen years (2007–2021)
Authors: Seyoum Wasihun , Tora Ephrem 
Published: February 2023

Abstract
Background
Foot and Mouth disease (FMD) is an acute contagious and highly infectious disease of domesticated and wild cloven-hoofed animals characterized by the appearance of vesicular lesions at the epithelium of the mouth, nares, muzzle, feet and udder, causing repeated outbreaks every year in Ethiopia, thereby causing production loss and the banning of exportation of livestock, products and their by-products. The prevalence of foot and mouth disease in Ethiopia has been reported from different parts of the country, but a pooled quantitative estimate of foot and mouth disease has not been done so far; therefore this meta-analysis sought to determine FMD status in Ethiopia.

Main body
Literature search was conducted by the main search engines and indexing services: Google, Google Scholar, PubMed, and Science Direct. Additionally, university repositories were discovered to retrieve unpublished MSc theses. All studies dealt with the prevalence of FMD. Raw data were extracted in Microsoft Excel and then imported into R Studio. Random effects model was used to pool estimates of outcomes at 95% confidence interval. Heterogeneity level was computed by Higgins’s I2 statistics. Publication bias was checked using funnel plots for standard error augmented by Begg’s and Egger’s tests. In total, 27 reports with 13,510 cattle were included in this study. An estimate of prevalence across reviews for the entire literature collected from the period 2007 to 2021 was 21.39% (16.53–26.56). Sub-analysis for herd size, animal composition, age group and sex of cattle identified as potential significant factors for FMD. FMD prevalence in cattle at early age and adult age was 19.5% and 14.6%, respectively (P < 0.01). Compared to intensive production, FMD occurrence was 4.3 times higher in extensive production (P value = 0.003).

Conclusions
FMD is prevalent in Ethiopian cattle, and the disease is a list A disease which could affect the export of live animals and their products since FMD is a trans-boundary disease. Therefore, it is imperative to have strategic implementation of effective prevention, control, and robust eradication policies.
Polygenic risk scores enhance prediction of body mass index increase in individuals with a first episode of psychosis
Authors: Muntané Gerard , Vázquez-Bourgon Javier , Sada Ester , Martorell Lourdes , Papiol Sergi , Bosch Elena , Navarro Arcadi , Crespo-Facorro Benedicto , Vilella Elisabet 
Published: February 2023

Abstract

Background
Individuals with a first episode of psychosis (FEP) show rapid weight gain during the first months of treatment, which is associated with a reduction in general physical health. Although genetics is assumed to be a significant contributor to weight gain, its exact role is unknown.

Methods
We assembled a population-based FEP cohort of 381 individuals that was split into a Training (n = 224) set and a Validation (n = 157) set to calculate the polygenic risk score (PRS) in a two-step process. In parallel, we obtained reference genome-wide association studies for body mass index (BMI) and schizophrenia (SCZ) to examine the pleiotropic landscape between the two traits. BMI PRSs were added to linear models that included sociodemographic and clinical variables to predict BMI increase (∆BMI) in the Validation set.

Results
The results confirmed considerable shared genetic susceptibility for the two traits involving 449 near-independent genomic loci. The inclusion of BMI PRSs significantly improved the prediction of ∆BMI at 12 months after the onset of antipsychotic treatment by 49.4% compared to a clinical model. In addition, we demonstrated that the PRS containing pleiotropic information between BMI and SCZ predicted ∆BMI better at 3 (12.2%) and 12 months (53.2%).

Conclusions
We prove for the first time that genetic factors play a key role in determining ∆BMI during the FEP. This finding has important clinical implications for the early identification of individuals most vulnerable to weight gain and highlights the importance of examining genetic pleiotropy in the context of medically important comorbidities for predicting future outcomes.