bluuebunny/crossref_metadata_2025_split huggingface dataset:
Luminescence dating of heated quartz extracted from burnt clay and pottery excavated from the Lingjiatan archaeological site, China
Authors: Wang Chun-Xin , Zhang Xiaolei , Zhang Yunyi , Wu Youjin , Huang Chang , Fan Anchuan 
Published: August 2022

This study utilizes OSL-SAR, TL-SAR, and TL-MAAD methods to date heated quartz extracted from burnt clay and pottery samples from the Lingjiatan archaeological site, China. The OSL components of the heated quartz were determined by deconvoluting the CW-OSL curve, and the Fast Ratio value was used to distinguish whether the initial OSL signal was dominated by the fast component. The results show two types of quartz OSL characteristics in the initial signals: Type I is dominated by the fast component (Fast Ratio values &gt; 10), while Type II is dominated by the medium and slow components (Fast Ratio values &lt; 10). Type I samples show bright OSL signals, and a preheat plateau appears from a relatively low temperature. The recuperation is negligible, and reliable equivalent doses can be obtained using the conventional OSL-SAR measurement conditions. In contrast, the OSL signal of Type II samples is relatively dim, and the preheat plateau appears from a much higher temperature than in Type I samples. The recuperation of Type II samples increases significantly at higher preheat temperatures. Significant De underestimation of Type II samples was observed at lower preheat temperatures. It is noted that the thermal transfer effect can be attenuated by increasing the OSL stimulation temperature. Therefore, a modified OSL-SAR measurement condition, with higher preheat, cut-heat and stimulation temperatures, was used to date Type II samples. The OSL-SAR ages of most of these two types of samples agree well with the independent 14C ages, demonstrating that OSL-SAR can be used to date heated archaeological materials at high firing temperatures (∼900°C). The Lingjiatan archaeological site was determined to be approximately 5.4–5.8 ka BP 2022.
Identification of programmed cell death-related gene signature and associated regulatory axis in cerebral ischemia/reperfusion injury
Authors: Shu Jun , Yang Lu , Wei Wenshi , Zhang Li 
Published: August 2022

Background: Numerous studies have suggested that programmed cell death (PCD) pathways play vital roles in cerebral ischemia/reperfusion (I/R) injury. However, the specific mechanisms underlying cell death during cerebral I/R injury have yet to be completely clarified. There is thus a need to identify the PCD-related gene signatures and the associated regulatory axes in cerebral I/R injury, which should provide novel therapeutic targets against cerebral I/R injury.Methods: We analyzed transcriptome signatures of brain tissue samples from mice subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and matched controls, and identified differentially expressed genes related to the three types of PCD(apoptosis, pyroptosis, and necroptosis). We next performed functional enrichment analysis and constructed PCD-related competing endogenous RNA (ceRNA) regulatory networks. We also conducted hub gene analysis to identify hub nodes and key regulatory axes.Results: Fifteen PCD-related genes were identified. Functional enrichment analysis showed that they were particularly associated with corresponding PCD-related biological processes, inflammatory response, and reactive oxygen species metabolic processes. The apoptosis-related ceRNA regulatory network was constructed, which included 24 long noncoding RNAs (lncRNAs), 41 microRNAs (miRNAs), and 4 messenger RNAs (mRNAs); the necroptosis-related ceRNA regulatory network included 16 lncRNAs, 20 miRNAs, and 6 mRNAs; and the pyroptosis-related ceRNA regulatory network included 15 lncRNAs, 18 miRNAs, and 6 mRNAs. Hub gene analysis identified hub nodes in each PCD-related ceRNA regulatory network and seven key regulatory axes in total, namely, lncRNA Malat1/miR-181a-5p/Mapt, lncRNA Malat1/miR-181b-5p/Mapt, lncRNA Neat1/miR-181a-5p/Mapt, and lncRNA Neat1/miR-181b-5p/Mapt for the apoptosis-related ceRNA regulatory network; lncRNA Neat1/miR-181a-5p/Tnf for the necroptosis-related ceRNA regulatory network; lncRNA Malat1/miR-181c-5p/Tnf for the pyroptosis-related ceRNA regulatory network; and lncRNAMalat1/miR-181a-5p for both necroptosis-related and pyroptosis-related ceRNA regulatory networks.Conclusion: The results of this study supported the hypothesis that these PCD pathways (apoptosis, necroptosis, pyroptosis, and PANoptosis) and crosstalk among them might be involved in ischemic stroke and that the key nodes and regulatory axes identified in this study might play vital roles in regulating the above processes. This may offer new insights into the potential mechanisms underlying cell death during cerebral I/R injury and provide new therapeutic targets for neuroprotection.
Functional characterization of MEKK3 in the intestinal immune response to bacterial challenges in grass carp (Ctenopharyngodon idella)
Authors: Qu Fufa , Zeng Xuan , Liu Zhenzhen , Guo Meixing , Zhang Xia , Cao Shenping , Zhou Yonghua , He Zhimin , Tang Jianzhou , Mao Zhuangwen , Yang Yalin , Zhou Zhigang , Liu Zhen 
Published: August 2022

Mitogen-activated protein kinase kinase kinase 3 (MEKK3) is an evolutionarily conserved Ser/Thr protein kinase of the MEKK family that is essential for the host immune response to pathogen challenges in mammals. However, the immune function of MEKK3s in lower vertebrate species, especially in bony fish, remains largely unknown. In this study, a fish MEKK3 (designated CiMEKK3) gene was cloned and identified from grass carp (Ctenopharyngodon idella). The present CiMEKK3 cDNA encoded a 620 amino acid polypeptide containing a conserved S-TKc domain and a typical PB1 domain. Several potential immune-related transcription factor-binding sites, including activating protein 1 (AP-1), nuclear factor kappa B (NF-κB) and signal transducer and activator of downstream transcription 3 (STAT3), were observed in the 5’ upstream DNA sequence of CiMEKK3. A phylogenetic tree showed that CiMEKK3 exhibits a close evolutionary relationship with MEKK3s from Cyprinus carpio and Carassius auratus. Quantitative real-time PCR analysis revealed that CiMEKK3 transcripts were widely distributed in all selected tissues of healthy grass carp, with a relatively high levels observed in the gill, head kidney and intestine. Upon in vitro challenge with bacterial pathogens (Aeromonas hydrophila and Aeromonas veronii) and pathogen-associated molecular patterns (PAMPs) (lipopolysaccharide (LPS), peptidoglycan (PGN), L-Ala-γ-D-Glu-mDAP (Tri-DAP) and muramyl dipeptide (MDP)), the expression levels of CiMEKK3 in the intestinal cells of grass carp were shown to be significantly upregulated in a time-dependent manner. In vivo injection experiments revealed that CiMEKK3 transcripts were significantly induced by MDP challenge in the intestine; however, these effects could be inhibited by the nutritional dipeptides carnosine and Ala-Gln. Moreover, subcellular localization analysis and luciferase reporter assays indicated that CiMEKK3 could act as a cytoplasmic signal-transducing activator involved in the regulation of NF-κB and MAPK/AP-1 signaling cascades in HEK293T cells. Taken together, these findings strongly suggest that CiMEKK3 plays vital roles in the intestinal immune response to bacterial challenges, which will aid in understanding the pathogenesis of inflammatory bowel disease in bony fish.
Nudix Hydroxylase 15 Mutations Strongly Predict Thiopurine-Induced Leukopenia Across Different Asian Ethnicities: Implications for Screening in a Diverse Population
Authors: Khoo Xin-Hui , Wong Shin Yee , Ibrahim Nik Razima Wan , Ng Ruey Terng , Chew Kee Seang , Lee Way Seah , Wong Zhi Qin , Raja Ali Raja Affend , Shahrani Shahreedhan , Leow Alex Hwong-Ruey , Hilmi Ida Normiha 
Published: August 2022

Background and AimsThiopurines, which are immunosuppressive drugs for maintaining remission for inflammatory bowel disease, are known to cause myelotoxicity in patients with Nudix Hydroxylase 15 (NUDT15) genetic variants in some Asian countries with monoethnic populations. We aimed to investigate the association of NUDT15 variants with leukopenia in a multiethnic population in Southeast Asia.MethodsPatients with a confirmed diagnosis of inflammatory bowel disease were recruited. We collected demographic and clinical characteristics and whole blood counts before and after initiating thiopurines. Thiopurine S-methyltransferase (TPMT) and NUDT15 genotypes were analyzed with the single nucleotide polymorphisms (SNPs) genotyping assay. Leukopenia was defined as a white blood cell (WBC) count &lt; 3,000/μl.ResultsIn this study, 19 (18.6%) of the 102 patients who had adequate thiopurine therapy experienced leukopenia, 11 patients (57.9%) had NUDT15 c.415C &gt; T variants, 2 patients (10.5%) had NUDT15 c.52G &gt; A variants while one (5.3%) had a TPMT variation. Individually, NUDT15 c.415C &gt; T had a sensitivity and specificity of 57.9% and 94.0% (odds ratio [OR] = 21.45, 95% CI 5.94–77.41, p &lt; 0.001), respectively, for predicting thiopurine-induced leukopenia, while NUDT15 c.52G &gt; A was only observed in patients with leukopenia. As compared with patients with wild-type NUDT15, both NUDT15 variations had a combined sensitivity and specificity of 68.4% and 94%, respectively (OR = 33.80, 95% CI 8.99–127.05, p &lt; 0.001), for predicting thiopurine-induced leukopenia as well as a shorter onset to leukopenia (median onset [months] 2.0 vs. 5.5; p = 0.045). Sub-group analysis showed that both NUDT15 variations were strongly associated with leukopenia among the Chinese and Indians but not among the Malays.ConclusionNudix Hydroxylase 15 variants strongly predicted thiopurine-induced leukopenia across a multiethnic Southeast Asian population, particularly among the Chinese and Indians.
Technology-based therapy-response evaluation of axial motor symptoms under daily drug regimen of patients with Parkinson’s disease
Authors: Wu Zhuang , Hong Ronghua , Li Shuangfang , Peng Kangwen , Lin Ao , Gao Yichen , Jin Yue , Su Xiaoyun , Zhi Hongping , Guan Qiang , Pan Lizhen , Jin Lingjing 
Published: August 2022

BackgroundAxial disturbances are the most disabling symptoms of Parkinson’s disease (PD). Kinect-based objective measures could extract motion characteristics with high reliability and validity.PurposeThe present research aimed to quantify the therapy–response of axial motor symptoms to daily medication regimen and to explore the correlates of the improvement rate (IR) of axial motor symptoms based on a Kinect camera.Materials and methodsWe enrolled 44 patients with PD and 21 healthy controls. All 65 participants performed the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale part III and the Kinect-based kinematic evaluation to assess arising from a chair, gait, posture, and postural stability before and after medication. Spearman’s correlation analysis and multiple linear regression model were performed to explore the relationships between motor feature IR and clinical data.ResultsAll the features arising from a chair (P = 0.001), stride length (P = 0.001), velocity (P &lt; 0.001), the height of foot lift (P &lt; 0.001), and turning time (P = 0.001) improved significantly after a daily drug regimen in patients with PD. In addition, the anterior trunk flexion (lumbar level) exhibited significant improvement (P = 0.004). The IR of the axial motor symptoms score was significantly correlated with the IRs of kinematic features for gait velocity, stride length, foot lift height, and sitting speed (rs = 0.345, P = 0.022; rs = 0.382, P = 0.010; rs = 0.314, P = 0.038; rs = 0.518, P &lt; 0.001, respectively). A multivariable regression analysis showed that the improvement in axial motor symptoms was associated with the IR of gait velocity only (β = 0.593, 95% CI = 0.023–1.164, P = 0.042).ConclusionAxial symptoms were not completely drug-resistant, and some kinematic features can be improved after the daily medication regimen of patients with PD.
A randomized single-blind controlled trial of a prototype digital polytherapeutic for tinnitus
Authors: Searchfield Grant D. , Sanders Philip J. 
Published: August 2022

ObjectiveThis randomized single-blind controlled trial tested the hypothesis that a prototype digital therapeutic developed to provide goal-based counseling with personalized passive and active game-based sound therapy would provide superior tinnitus outcomes, and similar usability, to a popular passive sound therapy app over a 12 week trial period.MethodsThe digital therapeutic consisted of an app for iPhone or Android smartphone, Bluetooth bone conduction headphones, neck pillow speaker, and a cloud-based clinician dashboard to enable messaging and app personalization. The control app was a popular self-help passive sound therapy app called White Noise Lite (WN). The primary outcome measure was clinically meaningful change in Tinnitus Functional Index (TFI) between baseline and 12 weeks of therapy. Secondary tinnitus measures were the TFI total score and subscales across sessions, rating scales and the Client Oriented Scale of Improvement in Tinnitus (COSIT). Usability of the US and WN interventions were assessed using the System Usability Scale (SUS) and the mHealth App Usability Questionnaire (MAUQ). Ninety-eight participants who were smartphone app users and had chronic moderate-severe tinnitus (&gt;6 months, TFI score &gt; 40) were enrolled and were randomly allocated to one of the intervention groups. Thirty-one participants in the USL group and 30 in the WN group completed 12 weeks of trial.ResultsMean changes in TFI for the USL group at 6 (16.36, SD 17.96) and 12 weeks (17.83 points, SD 19.87) were clinically meaningful (&gt;13 points reduction), the mean change in WN scores were not clinically meaningful (6 weeks 10.77, SD 18.53; 12 weeks 10.12 points, SD 21.36). A statistically higher proportion of USL participants achieved meaningful TFI change at 6 weeks (55%) and 12 weeks (65%) than the WN group at 6 weeks (33%) and 12 weeks (43%). Mean TFI, rating and COSIT scores favored the US group but were not statistically different from WN. Usability measures were similar for both groups.ConclusionsThe USL group demonstrated a higher proportion of responders than the WN group. The usability of the USL therapeutic was similar to the established WN app. The digital polytherapeutic demonstrated significant benefit for tinnitus reduction supporting further development.
Efficacy and safety of indocyanine green tracer-guided lymph node dissection in minimally invasive radical gastrectomy for gastric cancer: A systematic review and meta-analysis
Authors: Zhao Jixiang , Li Ke , Wang Zikang , Ke Qingqing , Li Jiapu , Zhang Yizhen , Zhou Xiaojiang , Zou Yunzhi , Song Conghua 
Published: August 2022

BackgroundThe implementation of indocyanine green (ICG) tracer-guided lymph node dissection is still in the preliminary stages of laparoscopic surgery, and its safety and efficacy for gastric cancer remain unclear.MethodsA systematic review was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and Scopus to identify relevant subjects from inception to June 2022. The core indicators were the total number of harvested lymph nodes and the safety of the laparoscopic gastrectomy with ICG. A meta-analysis was performed to estimate the pooled weighted mean difference (WMD) and 95% confidence interval (CI).ResultsThirteen studies and 2,027 participants were included (642 for the ICG-group and 1,385 for the non-ICG group). The mean number of lymph nodes dissected in the ICG group was significantly greater than that in the non-ICG group (WMD = 6.24, 95% CI: 4.26 to 8.22, P &lt;0.001). However, there was no significant difference in the mean number of positive lymph nodes dissected between the ICG and the non-ICG groups (WMD = 0.18, 95% CI: −0.70 to 1.07, P = 0.879). Additionally, ICG gastrectomy did not increase the risk in terms of the operative time, estimated blood loss, and postoperative complications.ConclusionICG tracer with favorable safety increases the number of harvested lymph nodes but not the number of positive lymph nodes in laparoscopic gastrectomy. More high-quality, large-sample-size randomized controlled trials are still needed to enhance this evidence.
PD-L1 expression, tumor mutational burden, and immune cell infiltration in non-small cell lung cancer patients with epithelial growth factor receptor mutations
Authors: Ma Tiantian , Jiao Jin , Huo Ran , Li Xiaofang , Fang Guotao , Zhao Qi , Liu Weiwei , Han Xiao , Xi Chenglin , Wang Yanan , Shang Yanhong 
Published: August 2022

BackgroundImmunotherapy using programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors seems less effective in non-small cell lung cancer (NSCLC) patients with epithelial growth factor receptor (EGFR) mutations. Varied responses to PD-1/PD-L1 inhibitors have recently been observed in NSCLC patients harboring different types of EGFR mutations. Some EGFR-mutated NSCLC patients may benefit from PD-1/PD-L1 inhibitors. At present, PD-L1 expression, tumor mutational burden (TMB), and tumor immune microenvironment (TIME) are biomarkers for predicting the efficacy of PD-1/PD-L1 inhibitors in NSCLC patients. We retrospectively evaluated PD-L1 expression, TMB, and immune cell infiltration in NSCLC patients with EGFR mutation subtypes.MethodsPD-L1 expression, TMB, and the abundance of immune cell infiltration in NSCLC patients were evaluated in public databases and clinical samples. TMB was detected using the NGS technique, PD-L1 was detected using immunohistochemistry, and the abundance of immune cell infiltration in NSCLC samples was detected using multiple immunohistochemistry.ResultsPD-L1 expression and TMB were lower in EGFR-mutated NSCLCs than in wild-type patients. Differences in the abundance of immune cell infiltration were also observed between EGFR-mutated and wild-type NSCLC. The expression of PD-L1, TMB, and abundance of immune cell infiltration were different in patients harboring different subtypes of EGFR mutations. Patients with uncommon EGFR mutations, especially the G719X mutation, showed higher TMB and expressions of PD-L1 than classical EGFR mutations. M1 macrophages were higher in uncommon EGFR mutations than classical EGFR mutations.ConclusionsThe expression of PD-L1 and TMB in uncommon EGFR-mutated NSCLCs, especially the G719X mutation, were higher than those for classical EGFR-mutated NSCLCs and similar to EGFR wild-type. The abundance of immune cell infiltration in uncommon EGFR-mutated NSCLCs was similar to that in EGFR wild-type. Our findings suggest that uncommon EGFR-mutated NSCLCs may benefit from PD-1/PD-L1 inhibitors.
Clinical application of parathyroid autotransplantation in endoscopic radical resection of thyroid carcinoma
Authors: Zhang Qi , Qu Kun-Peng , Wang Ze-Sheng , Gao Jing-Wei , Zhang Yu-Peng , Cao Wei-Jia 
Published: August 2022

PurposeThis study aimed to examine the effect of selective inferior parathyroid gland autotransplantation on central lymph node dissection(CLND) and incidence of postoperative hypoparathyroidism in patients undergoing endoscopic radical resection of thyroid carcinoma.MethodsThe data of 310 patients undergoing endoscopic radical resection of thyroid carcinoma will be retrospectively analyzed. The patients will be divided into the experimental group and the control group according to whether they combined with parathyroid autotransplantation. Statistics of the incidence rate of postoperative hypoparathyroidism, the concentration of PTH and Calcium in the systemic circulation at different time points in the two groups, the concentration of PTH in the cubital fossa vein in the transplantation region in the experimental group, and the number of central lymph nodes and positive lymph nodes dissection will be carried out.ResultsThe incidence rate of temporary and permanent hypoparathyroidism in the experimental group was 33.75% and 0.625%, respectively, and in the control group was 22% and 5%, respectively; its difference was statistically significant (X2 = 10.255, P=0.006). Parathyroid autotransplantation increased incidence of transient hypoparathyroidism (OR, 1.806; Cl, 1.088-2.998; P=0.022), and lower incidence of permanent hypoparathyroidism (OR, 0.112; Cl, 0.014-0.904; P=0.040). The diameters of thyroid cancer nodules was not associated with the occurrence of transient hypoparathyroidism (OR, 0.769; Cl, 0.467-1.265; P=0.301) or permanent hypoparathyroidism (OR, 1.434; Cl, 0.316-6.515; P=0.641). Comparison of systemic circulation PTH, between the two groups showed that the PTH of patients in the experimental group was higher than that in the control group from 1 week to 12 months after the operation, and the difference was statistically significant (P&lt;0.05). In the experimental group, from 1 week to 12 months after surgery, PTH concentrations was significantly higher in the cubital fossa of the transplantation side than in the contralateral side, and the differences were statistically significant (P&lt;0.05). The mean number of central lymph node dissected per patient was significantly higher in the experimental group (7.94 ± 3.03 vs. 6.99 ± 2.86; P &lt;0.05); The mean number of positive nodes per patient was significantly higher in the experimental group (3.16 ± 1.86 vs. 2.53 ± 1.59; P &lt;0.05).ConclusionsIn endoscopic radical resection of thyroid carcinoma, parathyroid autotransplantation is more beneficial to postoperative parathyroid glands function recovery, effectively preventing postoperative permanent hypoparathyroidism and realizing more thorough CLND.
The clinical impact of endoscopic ultrasound-guided fine-needle aspiration on the patients with low-risk pancreatic cystic lesions
Authors: Pan Shubo , Liu Jie , Guo Jiefang , Zhu Qilin , Wang Liangjing , Shi Xiaohua 
Published: August 2022

Background and aimsEndoscopic ultrasound (EUS) is playing a more and more important role in the management of pancreatic cystic lesion (PCLs). The aim of our study was to evaluate the clinical impact of EUS and EUS guided fine needle aspiration (FNA) on patients with low-risk PCLs.Materials and methodsLow-risk PCL patients who underwent EUS-FNA in 2 edoscopic centers were retrospectively collected and analyzed. The clinical impact of EUS-FNA on these patients was analyzed and the predictors for significance EUS-FNA (defined by diagnosis and treatment method change, new high-risk feature identified after imaging scans) were analyzed by logistic regression analyses.ResultsFrom July 2004 to February 2017, 186 patients with low-risk PCLs were included. The study cohort had a mean age of 52.4 ± 15.9 years (range: 19-86 years) with 89 (47.8%) male patients included. The clinical significance of EUS-FNAs was observed in 74 patients (39.8%). The presumed diagnoses of PCLs by imaging were changed in 51 (51/74, 68.9%) patients. Nineteen (19/74, 25.7%) new high-risk features were identified by EUS-FNA, and four patients (4/74, 5.4%) underwent surgery due to suspicious or malignant cytology. Based on multivariate analysis, large cyst size [odds ratio (OR): 1.12, 95% confidence interval (CI): 1.02–1.19, P = 0.033], young age (OR: 0.94, 95% CI: 0.91–0.99, P = 0.041) and BMI over 25 (OR: 3.15, 95% CI: 1.29–7.86, P = 0.013) were independent predictors of clinical significance for EUS-FNA. The optimal age and cyst size to predict significance EUS-FNA was 46.0 years and 2.3cm.ConclusionsOn the basis of a 2-center retrospective study, EUS-FNA was clinically significant in about 40% of low-risk PCLs, especially in young, large cyst size, and overweight patients.