bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of ambient PM2.5 exposure on survival of lung cancer patients after lobectomy
Authors: Liu Changpeng , Yang Dongjian , Liu Yuxi , Piao Heng , Zhang Tao , Li Xi , Zhao Erjiang , Zhang Di , Zheng Yan , Tang Xiance 
Published: March 2023

AbstractExposure to fine particulate matter (PM2.5) is linked to lung cancer incidence and mortality. However, the impact of PM2.5 exposure on lung cancer patients after lobectomy, which remains the primary treatment for early-stage lung cancer, is unknown. Therefore, we investigated the correlation between PM2.5 exposure and the survival of lung cancer patients after lobectomy. This study included 3,327 patients with lung cancer who underwent lobectomy procedures. We converted residential addresses into coordinates and estimated individual patients' daily PM2.5 and O3 exposure levels. A Cox multivariate regression model was used to analyze the specific monthly association between PM2.5 exposure and lung cancer survival. Every 10 μg/m3 increase in monthly PM2.5 concentration in the first and second months after lobectomy increased the risk of death (hazard ratio [HR]: 1.043, 95% confidence interval [CI]: 1.019–1.067 and HR: 1.036, 95% CI: 1.013–1.060, respectively). Non-smokers, younger patients, and patients with longer hospitalization durations had worse survival rates when exposed to greater concentrations of PM2.5. High postoperative PM2.5 exposure immediately after lobectomy reduced the survival of patients with lung cancer. Patients living in areas with high PM2.5 should be offered the opportunity to transfer to areas with better air quality after undergoing lobectomies, to prolong their survival times.
Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury
Authors: Li Shengnan , Chen Shaofeng , Wang Yajun , Hu Xingjuan , Wang Ying , Wu Zhaochun , Huang Shaoting , He Jiawen , Deng Fu , Zhao Bin , Ma Guoda , Li You 
Published: March 2023

AbstractThe miRNA-181 (miR-181) family regulates neuronal persistence during cerebral ischemia/reperfusion injury (CI/RI). Since the effect of miR-181d on CI/RI has never been studied, the current work sought to determine the involvement of miR-181d in neuronal apoptosis after brain I/R injury. To replicate in vivo and in vitro CI/RI, a transient middle cerebral artery occlusion (tMCAO) model in rats and an oxygen-glucose deficiency/reoxygenation (OGD/R) model in neuro 2A cells were developed. In both in vivo and in vitro stroke models, the expression of miR-181d was considerably higher. miR-181d suppression reduced apoptosis and oxidative stress in OGD/R-treated neuroblastoma cells, but miR-181d overexpression increased both. Furthermore, it was observed that miR-181d has a direct target in dedicator of cytokinesis 4 (DOCK4). The overexpression of DOCK4 partially overcame cell apoptosis and oxidative stress induced by miR-181d upregulation and OGD/R injury. Furthermore, the DOCK4 rs2074130 mutation was related to lower DOCK4 levels in ischemic stroke (IS) peripheral blood and higher susceptibility to IS. These findings suggest that downregulating miR-181d protects neurons from ischemic damage by targeting DOCK4, implying that the miR-181d/DOCK4 axis might be a novel therapeutic target for IS.
Graphical Abstract
Minimizing invasiveness and simplifying the surgical procedure for upper and middle early gastric cancer with near-infrared light and organ traction
Authors: Nagano Shinnosuke , Ushimaru Yuki , Kawabata Ryohei , Kitagawa Akihiro , Ohara Nobuyoshi , Miyake Yuichiro , Tomihara Hideo , Maeda Sakae , Noura Shingo , Miyamoto Atsushi , Nishikawa Kazuhiro 
Published: March 2023

Abstract
Background
Surgeons are often faced with optimal resection extent and reconstructive method problems in laparoscopic gastrectomy for gastric cancer in the upper and middle body of the stomach. Indocyanine green (ICG) marking and Billroth I (B-I) reconstruction were used to solve these problems with the organ retraction technique.

Case presentation
A 51-year-old man with upper gastrointestinal endoscopy revealed a 0-IIc lesion in the posterior wall of the upper and middle gastric body 4 cm from the esophagogastric junction. Clinical T1bN0M0 (clinical stage IA) was the preoperative diagnosis. Laparoscopic distal gastrectomy (LDG) and D1 + lymphadenectomy was decided to be performed considering postoperative gastric function preservation. The ICG fluorescence method was used to determine the accurate tumor location since the determination was expected to be difficult to the extent of optimal resection with intraoperative findings. By mobilizing and rotating the stomach, the tumor in the posterior wall was fixed in the lesser curvature, and as large a residual stomach as possible was secured in gastrectomy. Finally, delta anastomosis was performed after increasing gastric and duodenal mobility sufficiently. Operation time was 234 min and intraoperative blood loss was 5 ml. The patient was allowed to be discharged on postoperative day 6 without complications.

Conclusion
The indication for LDG and B-I reconstruction can be expanded to cases where laparoscopic total gastrectomy or LDG and Roux-en-Y reconstruction has been selected for early-stage gastric cancer in the upper gastric body by combining preoperative ICG markings and gastric rotation method dissection.
Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation
Authors: Todorova Vyara , Stauffacher Mia Fee , Ravotto Luca , Nötzli Sarah , Karademir Duygu , Ebner Lynn J. A. , Imsand Cornelia , Merolla Luca , Hauck Stefanie M. , Samardzija Marijana , Saab Aiman S. , Barros L. Felipe , Weber Bruno , Grimm Christian 
Published: March 2023

Abstract
Background
Major retinal degenerative diseases, including age-related macular degeneration, diabetic retinopathy and retinal detachment, are associated with a local decrease in oxygen availability causing the formation of hypoxic areas affecting the photoreceptor (PR) cells. Here, we addressed the underlying pathological mechanisms of PR degeneration by focusing on energy metabolism during chronic activation of hypoxia-inducible factors (HIFs) in rod PR.

Methods
We used two-photon laser scanning microscopy (TPLSM) of genetically encoded biosensors delivered by adeno-associated viruses (AAV) to determine lactate and glucose dynamics in PR and inner retinal cells. Retinal layer-specific proteomics, in situ enzymatic assays and immunofluorescence studies were used to analyse mitochondrial metabolism in rod PRs during chronic HIF activation.

Results
PRs exhibited remarkably higher glycolytic flux through the hexokinases than neurons of the inner retina. Chronic HIF activation in rods did not cause overt change in glucose dynamics but an increase in lactate production nonetheless. Furthermore, dysregulation of the oxidative phosphorylation pathway (OXPHOS) and tricarboxylic acid (TCA) cycle in rods with an activated hypoxic response decelerated cellular anabolism causing shortening of rod photoreceptor outer segments (OS) before onset of cell degeneration. Interestingly, rods with deficient OXPHOS but an intact TCA cycle did not exhibit these early signs of anabolic dysregulation and showed a slower course of degeneration.

Conclusion
Together, these data indicate an exceeding high glycolytic flux in rods and highlight the importance of mitochondrial metabolism and especially of the TCA cycle for PR survival in conditions of increased HIF activity.
Determination of the effect of collars containing 10% w/w imidacloprid and 4.5% w/w flumethrin (Seresto®) on the incidence of Leishmania and other canine vector-borne pathogen infections in Greece
Authors: Ligda Panagiota , Gizzarelli Manuela , Kostopoulou Despoina , Foglia Manzillo Valentina , Saratsis Anastasios , Saratsi Katerina , Michler Susan , Ringeisen Hannah , Boegel Annette , Schunack Bettina , Pollmeier Matthias , Kontrafouris Michalis , Tsatsaki Ourania , Oliva Gaetano , Sotiraki Smaragda 
Published: March 2023

Abstract
Background
The objective of this field study was to assess the effect of treating a considerable portion of a dog population naturally exposed to canine vector-borne pathogens (CVBPs) in endemic areas with a 10% w/w imidacloprid/4.5% w/w flumethrin collar (Seresto®) on the transmission of CVBPs and the resulting incidence of infection.

Methods
A total of 479 dogs from two sites were enrolled in the study. Collars were placed on all dogs continuously for 21 months, with replacement of the collar every 7 months. All dogs were examined, including body weight and blood/conjunctival swab collections, every 7 months. Serum samples were analysed for the presence of antibodies against Leishmania infantum, Ehrlichia canis and Anaplasma phagocytophilum. PCR assays were also performed on blood samples and conjunctival swab collected from the dogs for the presence of L. infantum, and on blood samples only for the presence of Ehrlichia spp. and Anaplasma spp. Sand flies were collected, identified to species level and molecularly tested for L. infantum throughout two vector activity seasons.

Results
The results showed that the Seresto collar was safe with continuous use. At study inclusion, 419, 370 and 453 dogs tested negative for L. infantum, Ehrlichia spp. and Anaplasma spp., respectively (353 dogs tested negative for any pathogen). Overall, 90.2% of the dogs were protected from L. infantum infection on both sites combined. The entomological survey confirmed the presence of competent vectors of L. infantum at all monitored locations, namely the sand flies Phlebotomus neglectus and Phlebotomus tobbi, both of which are regarded as the most important competent vectors in the Mediterranean basin. All captured sand flies tested negative for L. infantum. Protection against ticks and fleas was high, with only two dogs showing a low number of ticks and seven dogs having low numbers of fleas at single evaluation time points. Across the entire study population, a number of dogs became infected with tick-transmitted pathogens, but prevention of transmission was 93% for E. canis and 87.2% for Anaplasma spp. when all cases from both sites were combined.

Conclusions
The Seresto® (10% w/w imidacloprid/4.5% w/w flumethrin) collar significantly reduced the risk of CVBP transmission when compared to previously observed incidences of CVBP infections in two highly endemic areas under field conditions.

Graphical Abstract
Towards an entrepreneurial university model: evidence from the Palestine Polytechnic University
Authors: Awad Ibrahim M. , Salaimeh Meera Kh. 
Published: March 2023

AbstractThis study aims to introduce a proposed model for transforming the Palestine Polytechnic University (PPU) into an entrepreneurial university. Towards that end, a quantitative approach using statistical techniques of t test, ANOVA, Kruskal–Wallis test, and Pairwise comparisons supported by explanatory and qualitative discussions were utilized. The main findings show that the applicability of entrepreneurship at PPU was relatively fair for the aspects of the compatibility of curricula with the labor market needs, community relations and partnerships, academic exchange, entrepreneurship culture, entrepreneurial education, and university internationalization. Entrepreneurship as a policy objective was moderately acceptable for university policies and regulations, scientific research and innovation, and university leadership, but the university environment was less than moderate. The findings also show that the university leadership acknowledges the importance of achieving entrepreneurship, while they pay insufficient attention to the academic exchange. Offering other supportive funding resources can accelerate entrepreneurship. Given that, this study is likely to provide a proposed model to transform PPU into an entrepreneurial university and effectively achieve the university’s pioneering vision that contributes to the university’s development and presents this model to the decision makers.
Application of CRISPR-Based C-to-G Base editing in rice protoplasts
Authors: Lee Jimin , Oh Nuri , Yun Jae-Young , Choi Hee Soon , Seo Jang-Kyun , Kang Jin-Ho , Jung Choonkyun 
Published: March 2023

AbstractRecently, new types of base editors, C-to-G base editors (CGBEs), that enable cytosine transversions that are unachievable with cytosine base editors (CBEs) and adenosine base editors (ABEs), have been developed in human cells. However, despite their importance in crop genome editing, the efficacy of CGBEs has not yet been extensively evaluated. In our study, based on the previously reported plant-compatible CBE and human CGBE, we demonstrated that our monocot plant-compatible CGBEs (PcCGBEs) enable cytosine transversions (C-to-G) in rice protoplasts. For all targets tested, PcCGBEs (monocot plant-compatible CGBEs) appeared to have substantial levels of C-to-G editing activity. PcCGBE showed a much higher C-to-G base editing activity and C-to-G specificity among C-to-D conversions than the mini-version of PcCGBE. Our demonstration of PcCGBE could provide a platform for the further development of enhanced CGBEs for reliable application as a new crop breeding technology.
Cell-specific vulnerability to metabolic failure: the crucial role of parvalbumin expressing neurons in creatine transporter deficiency
Authors: Ghirardini Elsa , Sagona Giulia , Marquez-Galera Angel , Calugi Francesco , Navarron Carmen M. , Cacciante Francesco , Chen Siwei , Di Vetta Federica , Dadà Lorenzo , Mazziotti Raffaele , Lupori Leonardo , Putignano Elena , Baldi Pierre , Lopez-Atalaya Jose P. , Pizzorusso Tommaso , Baroncelli Laura 
Published: March 2023

AbstractMutations in the solute carrier family 6-member 8 (Slc6a8) gene, encoding the protein responsible for cellular creatine (Cr) uptake, cause Creatine Transporter Deficiency (CTD), an X-linked neurometabolic disorder presenting with intellectual disability, autistic-like features, and epilepsy. The pathological determinants of CTD are still poorly understood, hindering the development of therapies. In this study, we generated an extensive transcriptomic profile of CTD showing that Cr deficiency causes perturbations of gene expression in excitatory neurons, inhibitory cells, and oligodendrocytes which result in remodeling of circuit excitability and synaptic wiring. We also identified specific alterations of parvalbumin-expressing (PV+) interneurons, exhibiting a reduction in cellular and synaptic density, and a hypofunctional electrophysiological phenotype. Mice lacking Slc6a8 only in PV+ interneurons recapitulated numerous CTD features, including cognitive deterioration, impaired cortical processing and hyperexcitability of brain circuits, demonstrating that Cr deficit in PV+ interneurons is sufficient to determine the neurological phenotype of CTD. Moreover, a pharmacological treatment targeted to restore the efficiency of PV+ synapses significantly improved cortical activity in Slc6a8 knock-out animals. Altogether, these data demonstrate that Slc6a8 is critical for the normal function of PV+ interneurons and that impairment of these cells is central in the disease pathogenesis, suggesting a novel therapeutic venue for CTD.
CHIBA score: a novel model for predicting 3-month mortality in a cohort of Decompensated Liver Disease (DCLD)
Authors: Sathar Shanid Abdul , Vargheese Jijo 
Published: March 2023

Abstract
Background
Decompensated liver disease (DCLD) has high mortality, and its prediction is important to prognosticate and prioritize patients for liver transplantation. MELD, MELD variants, and CTP were widely tested for mortality prediction with few drawbacks. The aim of the study is to propose a new prognostic model for DCLD which is better than the existing scores.

Materials and methods
Retrospective study with 321 DCLD patients were enrolled. Patient relatives were telephonically contacted regarding date of death, and mortality at 3 months was assessed. Logistic regression was done, coefficient of beta of independent variables were found out, and a new CHIBA score was proposed.
CHIBA score = creatinine × 0.6 + HE × 0.4+ INR × 0.8 + bilirubin × 0.125 + ascites × 1.2) where C stands for creatinine, H for hepatic encephalopathy, I for INR, B for bilirubin, and A for ascites.

Results
CHIBA score has AUROC of 0.793 (at a cutoff of > 5.5, it has a sensitivity of 66% and specificity of 76%) compared to MELD-Na of 0.735 (cutoff > 25, sensitivity 65%, and specificity 72%); MELD of 0.727 (cutoff > 17 sensitivity of 80.37% and specificity of 55.14%); I-MELD of 0.72; MESO index of 0.72; and UKELD of 0.686. For validation, 214 patients were selected, and AUROC of CHIBA score in the validation cohort was 0.77. At a cutoff of > 5.5, it has a sensitivity of 60% and specificity of 77%.

Conclusion
CHIBA score is superior to MELD and MELD variants in predicting 3-month mortality, and it is validated in an external cohort. It can be calculated at bedside as it is a simple score with no logarithmic variables in it.
Anti–G Protein–Coupled Receptor, Class C Group 5 Member D Chimeric Antigen Receptor T Cells in Patients With Relapsed or Refractory Multiple Myeloma: A Single-Arm, Phase Ⅱ Trial
Authors: Xia Jieyun , Li Hujun , Yan Zhiling , Zhou Dian , Wang Ying , Qi Yuekun , Cao Jiang , Li Depeng , Cheng Hai , Sang Wei , Zhu Feng , Sun Haiying , Chen Wei , Qi Kunming , Yan Dongmei , Qiu Tingting , Qiao Jianlin , Yao Ruosi , Liu Yang , Wang Xue , Zhang Yanlei , Peng Shuixiu , Huang Chih-Hua , Zheng Junnian , Li Zhenyu , Chang Alex H. , Xu Kailin 
Published: March 2023

PURPOSE G protein–coupled receptor, class C group 5 member D (GPRC5D) is considered to be a promising surface target for multiple myeloma (MM) immunotherapy. Here, we report the efficacy and safety of anti-GPRC5D chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory (R/R) MM. METHODS This phase Ⅱ, single-arm study enrolled patients (18-70 years) with R/R MM. Lymphodepletion was performed before patients received 2 × 106/kg anti-GPRC5D CAR T cells. The primary end point was the proportion of patients who achieved an overall response. Safety was also evaluated in eligible patients. RESULTS From September 1, 2021, to March 23, 2022, 33 patients were infused with anti-GPRC5D CAR T cells. At a median follow-up of 5.2 months (range, 3.2‐8.9), the overall response rate was 91% (95% CI, 76 to 98; 30 of 33 patients), including 11 (33%) stringent complete responses, 10 (30%) complete responses, four (12%) very good partial responses, and five (15%) partial responses. Partial responses or better were observed in nine (100%) of nine patients with previous anti–B-cell maturation antigen (BCMA) CAR T-cell therapy, including two patients who had received repeated anti-BCMA CAR T-cell infusions with no responses at the last time. Grade 3 or higher hematologic toxicities were neutropenia (33 [100%]), anemia (17 [52%]), and thrombocytopenia (15 [45%]). Cytokine release syndrome occurred in 25 (76%) of 33 patients (all were grade 1 or 2), and neurotoxicities in three patients (one grade 2 and one grade 3 ICANSs and one grade 3 headache). CONCLUSION Anti-GPRC5D CAR T-cell therapy showed an encouraging clinical efficacy and manageable safety profile in patients with R/R MM. For patients with MM that progressed after anti-BCMA CAR T-cell therapy or that is refractory to anti-BCMA CAR T cell, anti-GPRC5D CAR T-cell therapy might be a potential alternative option.
Thyroid Function in Causal Relation to MRI Markers of Cerebral Small Vessel Disease: A Mendelian Randomization Analysis
Authors: Tian Yu , Yao Dongxiao , Jin Aoming , Wang Mengxing , Pan Yuesong , Wang Yongjun , Wang Yilong 
Published: March 2023

Abstract

Context
Observational studies have provided insufficient information on the association between thyroid function and the risk of cerebral small vessel disease (CSVD); moreover, the causality of this link is still unclear.

Objective
This study aims to investigate whether genetically predicted variation within thyroid function is causally associated with the risk of CSVD using 2-sample Mendelian randomization (MR) analysis.

Methods
In this 2-sample MR study with genome-wide association variants, we estimated the causal effects of genetically predicted thyrotropin (thyroid-stimulating hormone, TSH; n = 54 288), free thyroxine (FT4; n = 49 269), hypothyroidism (n = 51 823), and hyperthyroidism (n = 51 823) on 3 neuroimaging markers of CSVD, including white matter hyperintensity (WMH; n = 42 310), mean diffusivity (MD; n = 17 467), and fractional anisotropy (FA, n = 17 663). The primary analysis was conducted by the inverse variance–weighted MR method, followed by sensitivity analyses using MR-PRESSO, MR-Egger, weighted median, and weighted mode methods.

Results
Genetically increased TSH was associated with increased MD (β = .311, 95% CI 0.0763, 0.548, P = .01). Genetically increased FT4 was associated with increased FA (β = .540, 95% CI 0.222, 0.858, P &lt; .001). Sensitivity analyses using different MR methods showed similar directions but lower precision. No significant associations of hypothyroidism or hyperthyroidism with WMH, MD, or FA were found (all P &gt; .05).

Conclusion
This study indicated that genetically predicted increased TSH was associated with increased MD, as well as increased FT4 with increased FA, implying the causal effect of thyroid dysfunction on white matter microstructural injury. There were no significant causal relationships of hypothyroidism or hyperthyroidism with CSVD. Further investigations should verify these findings and clarify the underlying pathophysiological mechanisms.
Unilateral Thyroid Lobe Involvement of Graves Disease
Authors: Alzedaneen Yazan , Moxley Meaghan Chelsea , Reddy Rashmi , Munir Kashif M 
Published: March 2023

Abstract
A 30-year-old man presented with 3-year history of Graves disease. He was initially diagnosed after he developed unilateral proptosis and was initiated on methimazole 5 mg, on which he was currently euthyroid. Visible right-sided thyromegaly and trouble swallowing developed 2 months after presentation to our practice. Biochemical evaluation revealed suppressed TSH, normal free T4 and total T3, and elevated thyroid stimulating immunoglobulin with normal thyroid receptor antibody. An ultrasound of the thyroid demonstrated left-sided small nodules with right-sided thyromegaly. A nuclear medicine uptake scan revealed significantly greater uptake in the right thyroid lobe, with overall minimal uptake in the left lobe. The need for definitive therapy that would not exacerbate orbitopathy was discussed, and the patient elected for a right-sided hemithyroidectomy. Postoperative biochemical evaluation demonstrated biochemical euthyroidism despite continued elevation in thyroid stimulating immunoglobulin and newly elevated thyroid receptor antibody while remaining off methimazole. Graves disease can rarely involve a single thyroid lobe. Given the rarity, further investigation is needed to determine the natural course of this form of Graves disease.