bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative immunological plasma markers TRAIL, CSF1 and TIE2 predict survival after resection for biliary tract cancer
Authors: Jansson Hannes , Cornillet Martin , Sun Dan , Filipovic Iva , Sturesson Christian , O’Rourke Colm J. , Andersen Jesper B. , Björkström Niklas K. , Sparrelid Ernesto 
Published: June 2023

IntroductionSystemic inflammatory markers have been validated as prognostic factors for patients with biliary tract cancer (BTC). The aim of this study was to evaluate specific immunologic prognostic markers and immune responses by analyzing preoperative plasma samples from a large prospectively collected biobank.MethodsExpression of 92 proteins representing adaptive and innate immune responses was investigated in plasma from 102 patients undergoing resection for BTC 2009-2017 (perihilar cholangiocarcinoma n=46, intrahepatic cholangiocarcinoma n=27, gallbladder cancer n=29), by means of a high-throughput multiplexed immunoassay. Association with overall survival was analyzed by Cox regression, with internal validation and calibration. Tumor tissue bulk and single-cell gene expression of identified markers and receptors/ligands was analyzed in external cohorts.ResultsThree preoperative plasma markers were independently associated with survival: TRAIL, TIE2 and CSF1, with hazard ratios (95% confidence intervals) 0.30 (0.16-0.56), 2.78 (1.20-6.48) and 4.02 (1.40-11.59) respectively. The discrimination of a preoperative prognostic model with the three plasma markers was assessed with concordance-index 0.70, while the concordance-index of a postoperative model with histopathological staging was 0.66. Accounting for subgroup differences, prognostic factors were assessed for each type of BTC. TRAIL and CSF1 were prognostic factors in intrahepatic cholangiocarcinoma. In independent cohorts, TRAIL-receptor expression was higher in tumor tissue and seen in malignant cells, with TRAIL and CSF1 expressed by intra- and peritumoral immune cells. Intratumoral TRAIL-activity was decreased compared to peritumoral immune cells, while CSF1-activity was increased. The highest CSF1 activity was seen in intratumoral macrophages, while the highest TRAIL-activity was seen in peritumoral T-cells.DiscussionIn conclusion, three preoperative immunological plasma markers were prognostic for survival after surgery for BTC, providing good discrimination, even compared to postoperative pathology. TRAIL and CSF1, prognostic factors in intrahepatic cholangiocarcinoma, showed marked differences in expression and activity between intra- and peritumoral immune cells.
Genomic landscape of clinically advanced KRAS wild-type pancreatic ductal adenocarcinoma
Authors: Ashok Kumar Prashanth , Serinelli Serenella , Zaccarini Daniel J. , Huang Richard , Danziger Natalie , Janovitz Tyler , Basnet Alina , Sivapiragasam Abirami , Graziano Stephen , Ross Jeffrey S. 
Published: June 2023

IntroductionKRAS mutation is a common occurrence in Pancreatic Ductal Adenocarcinoma (PDA) and is a driver mutation for disease development and progression. KRAS wild-type PDA may constitute a distinct molecular and clinical subtype. We used the Foundation one data to analyze the difference in Genomic Alterations (GAs) that occur in KRAS mutated and wild-type PDA.MethodsComprehensive genomic profiling (CGP) data, tumor mutational burden (TMB), microsatellite instability (MSI) and PD-L1 by Immunohistochemistry (IHC) were analyzed.Results and discussionOur cohort had 9444 cases of advanced PDA. 8723 (92.37%) patients had KRAS mutation. 721 (7.63%) patients were KRAS wild-type. Among potentially targetable mutations, GAs more common in KRAS wild-type included ERBB2 (mutated vs wild-type: 1.7% vs 6.8%, p &lt;0.0001), BRAF (mutated vs wild-type: 0.5% vs 17.9%, p &lt;0.0001), PIK3CA (mutated vs wild-type: 2.3% vs 6.5%, p &lt;0.001), FGFR2 (mutated vs wild-type: 0.1% vs 4.4%, p &lt;0.0001), ATM (mutated vs wild-type: 3.6% vs 6.8%, p &lt;0.0001). On analyzing untargetable GAs, the KRAS mutated group had a significantly higher percentage of TP53 (mutated vs wild-type: 80.2% vs 47.6%, p &lt;0.0001), CDKN2A (mutated vs wild-type: 56.2% vs 34.4%, p &lt;0.0001), CDKN2B (mutated vs wild-type: 28.9% vs 23%, p =0.007), SMAD4 (mutated vs wild-type: 26.8% vs 15.7%, p &lt;0.0001) and MTAP (mutated vs wild-type: 21.7% vs 18%, p =0.02). ARID1A (mutated vs wild-type: 7.7% vs 13.6%, p &lt;0.0001 and RB1(mutated vs wild-type: 2% vs 4%, p =0.01) were more prevalent in the wild-type subgroup. Mean TMB was higher in the KRAS wild-type subgroup (mutated vs wild-type: 2.3 vs 3.6, p &lt;0.0001). High TMB, defined as TMB &gt; 10 mut/mB (mutated vs wild-type: 1% vs 6.3%, p &lt;0.0001) and very-high TMB, defined as TMB &gt;20 mut/mB (mutated vs wild-type: 0.5% vs 2.4%, p &lt;0.0001) favored the wild-type. PD-L1 high expression was similar between the 2 groups (mutated vs wild-type: 5.7% vs 6%,). GA associated with immune checkpoint inhibitors (ICPIs) response including PBRM1 (mutated vs wild-type: 0.7% vs 3.2%, p &lt;0.0001) and MDM2 (mutated vs wild-type: 1.3% vs 4.4%, p &lt;0.0001) were more likely to be seen in KRAS wild-type PDA.
Whole-tumor histogram analysis of apparent diffusion coefficients for predicting lymphovascular space invasion in stage IB-IIA cervical cancer
Authors: Cheng Jin-mei , Luo Wei-xiao , Tan Bang-guo , Pan Jian , Zhou Hai-ying , Chen Tian-wu 
Published: June 2023

ObjectivesTo investigate the value of apparent diffusion coefficient (ADC) histogram analysis based on whole tumor volume for the preoperative prediction of lymphovascular space invasion (LVSI) in patients with stage IB-IIA cervical cancer.MethodsFifty consecutive patients with stage IB-IIA cervical cancer were stratified into LVSI-positive (n = 24) and LVSI-negative (n = 26) groups according to the postoperative pathology. All patients underwent pelvic 3.0T diffusion-weighted imaging with b-values of 50 and 800 s/mm2 preoperatively. Whole-tumor ADC histogram analysis was performed. Differences in the clinical characteristics, conventional magnetic resonance imaging (MRI) features, and ADC histogram parameters between the two groups were analyzed. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of ADC histogram parameters in predicting LVSI.ResultsADCmax, ADCrange, ADC90, ADC95, and ADC99 were significantly lower in the LVSI-positive group than in the LVSI-negative group (all P-values &lt; 0.05), whereas no significant differences were reported for the remaining ADC parameters, clinical characteristics, and conventional MRI features between the groups (all P-values &gt; 0.05). For predicting LVSI in stage IB-IIA cervical cancer, a cutoff ADCmax of 1.75×10−3 mm2/s achieved the largest area under ROC curve (Az) of 0.750, followed by a cutoff ADCrange of 1.36×10−3 mm2/s and ADC99 of 1.75×10−3 mm2/s (Az = 0.748 and 0.729, respectively), and the cutoff ADC90 and ADC95 achieved an Az of &lt;0.70.ConclusionWhole-tumor ADC histogram analysis has potential value for preoperative prediction of LVSI in patients with stage IB-IIA cervical cancer. ADCmax, ADCrange, and ADC99 are promising prediction parameters.
Optimizing the xWORM assay for monitoring hookworm larvae motility
Authors: Lennox-Bulow Danica , Becker Luke , Loukas Alex , Seymour Jamie , Smout Michael 
Published: June 2023

Parasitic worms (helminths) infect almost all taxa across the animal kingdom, and pose significant challenges to public health and economies, particularly in developing countries. To address this problem, researchers have developed various tools to measure the motility and viability of helminths. However, the conditions used in anthelmintic screening assays are often not optimized, and can vary considerably between research teams. These unoptimized conditions may impact novel drug screens, as little is known about the effects of different conditions on the health of the target parasites. To improve future research, this study determined the effects of key assay parameters including, media type, media concentration, in-well parasite density, and assay duration on the infective third-stage larva (L3) of two types of hookworms, namely Nippostrongylus brasiliensis in rodents, and Necator americanus in humans. Conditions were screened over several days using the xCELLigence worm real-time motility assay (xWORM); a real-time impedance-based helminth motility assay using the xCELLigence system with 96-well microplates. While results varied depending on the species and media used, the study found that 500–1,000 L3/200-µL and a media concentration of 3.13–25% generally produced good to excellent assay conditions. The findings of this study can guide the future selection of xWORM assay parameters for novel drug trials involving these parasite species and serve as a suggested model for optimizing trial conditions for alternative parasite targets and assays.
Observed to expected lung area to head circumference ratio (O/E LHR) in fetuses with congenital anomalies of the kidney and urinary tract (CAKUT): assessment and evaluation as predictive factor for acute postnatal outcome—a single center study
Authors: Sourouni M. , Haisch L. , Oelmeier K. , Möllers M. , Willy D. , Sondern K. , Köster H. , Steinhard J. , Sandkötter J. , Klockenbusch W. , Schmitz R. , Potratz J. 
Published: June 2023

IntroductionTo assess the observed to expected lung area to head circumference ratio (O/E LHR) in fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) and to explore its value as a potential predictive factor for postnatal outcome.MethodsA retrospective single-center study was conducted on pregnancies complicated by CAKUT between 2007 and 2018. The lung-to-head ratio (LHR) was calculated for each fetus by two independent observers. Correlations between O/E LHR and various perinatal outcome factors were assessed with Spearman's rank correlation. Furthermore, nominal logistic regression was performed to assess O/E LHR as predictive factor for respiratory distress in newborn.ResultsOf 64 pregnancies complicated by CAKUT, 23 were terminated. In the 41 cases of continuation of pregnancy, newborn presenting respiratory distress with need for respiratory support in the delivery room showed earlier gestational age at onset of amniotic fluid abnormalities and at birth. Although median O/E LHR and median single deepest pocket (SDP) of amniotic fluid were significantly smaller in newborn that did develop respiratory distress with need of respiratory support in the delivery room, neither O/E LHR nor SDP were accurate predictors for the development of respiratory distress.ConclusionsOur data show that O/E LHR alone cannot serve as a predictive marker for fetal outcome in pregnancies complicated by CAKUT, though it might still be a helpful parameter together with detailed renal ultrasound evaluation, onset of amniotic fluid abnormality and SDP, particularly in its extreme values.
Perioperative active warming strategies in children: a protocol for a multicentre, prospective, randomized controlled trial
Authors: Qiao Lanxin , Wang Yaxin , Liang Yi , Xia Tian , Li Ling , Xiong Wei , Liu Bin , Feng Yifan , Liu Yan , Jin Xu , Zhang Jianmin 
Published: June 2023

IntroductionInadvertent perioperative hypothermia (IPH) refers to a core body temperature lower than 36.0 °C, which can contribute to many adverse events. The special physiological characteristics in children further increase the incidence of IPH. Therefore, it is very important to perform effective perioperative warming measures for children. Traditional passive warming measures with additional layers have limited thermal insulation effects. Active warming measures might be the better choice, and most measures have achieved good effects in adults. This study combines a variety of active warming measures to propose perioperative active warming strategies and aims to verify the feasibility and thermal insulation effects of perioperative active warming strategies in children.MethodsThis study is a multicentre, prospective, randomized controlled trial. From August 2022 to July 2024, 400 paediatric patients undergoing elective surgery will be recruited in four centres and randomly divided into the active warming strategies group and control group at a ratio of 1:1. The primary outcome is the perioperative cumulative hypothermia effect value (Σ ΔTi × Δti, i = 1…, n). Multiple complications covering the anaesthesia recovery period and postoperative hospitalization will be considered as secondary outcomes to comprehensively analyse the prognosis.Trial registrationClinicalTrials.gov identifier: ChiCTR2200062168. Registered on July 26th, 2022. Registered with the name of “Perioperative Active Warming Strategies in Children: A multicenter, prospective, randomized controlled trial”. URL:http://www.chictr.org.cn/showproj.aspx?proj=172778.
Robot-assisted resection of choledochal cyst in children
Authors: Jin Yi , Zhang Shuhao , Cai Duote , Zhang Yuebin , Luo Wenjuan , Chen Ken , Chen Qingjiang , Gao Zhigang 
Published: June 2023

BackgroundThe emergence of the robotic surgery system has assisted the further development of minimally invasive surgery by facilitating more delicate and precise complex procedures. The purpose of this study was to present a study of robot-assisted resection of the choledochal cyst and to discuss the technical points.MethodsIn total, 133 patients who were diagnosed with a choledochal cyst and underwent surgery from April 2020 to February 2022 in the Children's Hospital, Zhejiang University School of Medicine, were retrospectively analyzed. The data were collected including the clinical information of the patients, operative details, and postoperative outcomes.ResultsAmong these 133 patients, 99 underwent robot-assisted surgery and 34 underwent laparoscopic assisted surgery. The median operation time was 180 min, with an interquartile range (IQR) of 170–210 min for the robot-assisted group and 180 min with an IQR of 157.5–220 min in the laparoscopic assisted group (P = 0.290). The detection rate of 82.5% for the distal opening of the cystic type of choledochal cyst was higher in the robot-assisted group than that in the laparoscopic assisted group at 34.8% (P = 0.000). The postoperative hospital stay was shorter (P = 0.009) and the hospitalization expense was higher (P = 0.000) in the robot-assisted group than that of the laparoscopic assisted group. There was no significant difference between the two groups in terms of complications, postoperative indwelling days of the abdominal drainage tube, intraoperative blood loss, and postoperative fasting time (P &gt; 0.05).ConclusionsRobot-assisted resection of choledochal cyst is safe and feasible, it is ideal for the patient requiring a meticulous operation, and its postoperative recovery was shorter than for traditional laparoscopy.
Phosphoproteomic and proteomic profiling in post-infarction chronic heart failure
Authors: Wang Jiayue , Zhu Xiuhua , Wang Shenrui , Zhang Yingjie , Hua Wenjie , Liu Zhenyu , Zheng Yu , Lu Xiao 
Published: June 2023

Background: Post-infarction chronic heart failure is the most common type of heart failure. Patients with chronic heart failure show elevated morbidity and mortality with limited evidence-based therapies. Phosphoproteomic and proteomic analysis can provide insights regarding molecular mechanisms underlying post-infarction chronic heart failure and explore new therapeutic approaches.Methods and results: Global quantitative phosphoproteomic and proteomic analysis of left ventricular tissues from post-infarction chronic heart failure rats were performed. A total of 33 differentially expressed phosphorylated proteins (DPPs) and 129 differentially expressed proteins were identified. Bioinformatic analysis indicated that DPPs were enriched mostly in nucleocytoplasmic transport and mRNA surveillance pathway. Bclaf1 Ser658 was identified after construction of Protein-Protein Interaction Network and intersection with Thanatos Apoptosis Database. Predicted Upstream Kinases of DPPs based on kinase-substrate enrichment analysis (KSEA) app showed 13 kinases enhanced in heart failure. Proteomic analysis showed marked changes in protein expression related to cardiac contractility and metabolism.Conclusion: The present study marked phosphoproteomics and proteomics changes in post-infarction chronic heart failure. Bclaf1 Ser658 might play a critical role in apoptosis in heart failure. PRKAA1, PRKACA, and PAK1 might serve as potential therapeutic targets for post-infarction chronic heart failure.
Characterization of endophytic bacteriome diversity and associated beneficial bacteria inhabiting a macrophyte Eichhornia crassipes
Authors: Fan Di , Schwinghamer Timothy , Liu Shuaitong , Xia Ouyuan , Ge Chunmei , Chen Qun , Smith Donald L. 
Published: June 2023

IntroductionThe endosphere of a plant is an interface containing a thriving community of endobacteria that can affect plant growth and potential for bioremediation. Eichhornia crassipes is an aquatic macrophyte, adapted to estuarine and freshwater ecosystems, which harbors a diverse bacterial community. Despite this, we currently lack a predictive understanding of how E. crassipes taxonomically structure the endobacterial community assemblies across distinct habitats (root, stem, and leaf).MethodsIn the present study, we assessed the endophytic bacteriome from different compartments using 16S rRNA gene sequencing analysis and verified the in vitro plant beneficial potential of isolated bacterial endophytes of E. crassipes.Results and discussionPlant compartments displayed a significant impact on the endobacterial community structures. Stem and leaf tissues were more selective, and the community exhibited a lower richness and diversity than root tissue. The taxonomic analysis of operational taxonomic units (OTUs) showed that the major phyla belonged to Proteobacteria and Actinobacteriota (&gt; 80% in total). The most abundant genera in the sampled endosphere was Delftia in both stem and leaf samples. Members of the family Rhizobiaceae, such as in both stem and leaf samples. Members of the family Rhizobiaceae, such as Allorhizobium- Neorhizobium-Pararhizobium-Rhizobium were mainly associated with leaf tissue, whereas the genera Nannocystis and Nitrospira from the families Nannocystaceae and Nitrospiraceae, respectively, were statistically significantly associated with root tissue. Piscinibacter and Steroidobacter were putative keystone taxa of stem tissue. Most of the endophytic bacteria isolated from E. crassipes showed in vitro plant beneficial effects known to stimulate plant growth and induce plant resistance to stresses. This study provides new insights into the distribution and interaction of endobacteria across different compartments of E. crassipes Future study of endobacterial communities, using both culture-dependent and -independent techniques, will explore the mechanisms underlying the wide-spread adaptability of E. crassipesto various ecosystems and contribute to the development of efficient bacterial consortia for bioremediation and plant growth promotion.
Predictive validity of a parental questionnaire for identifying children with developmental language disorders
Authors: Auza B. Alejandra , Murata Chiharu , Peñaloza Christian 
Published: June 2023

BackgroundThe underdiagnosis of developmental language disorder (DLD) in children is a serious problem in developing countries with limited resources. It has long been noted that the concerns parents have about their children’s health and development are richly informative, and if this information can be used for diagnosis, it may provide a means to address the problem of underdiagnosis of DLD. This study aimed to quantify the utility of parental linguistic concern questions (PLCQ) on the identification of language disorders in monolingual Spanish-speaking children in Mexico. It also explored whether a combination of biological and environmental conditions questions (BECQ) might improve the performance of a screening test to identify DLD.MethodsA total of 680 monolingual Mexican Spanish-speaking children and their parents from urban areas in Mexico participated in the study. The distribution of responses to questions about DLD concerns was compared between 185 children diagnosed with DLD and 495 control subjects, and multiple logistic regression analysis was performed to select questions with high predictivity, based on the Akaike information criterion. The diagnostic utility of the questions was assessed by receiver operating characteristic (ROC) curves, stratum-specific likelihood ratios (SSLRs), and changes in pretest and post-test probabilities of DLD. A similar procedure was used to explore whether adding BECQ would improve the diagnostic utility of questions about DLD concerns using data of 128 children.ResultsFour questions regarding parental linguistic concerns were found to be useful in identifying children with DLD. When all four concerns were present, the SSLR was 8.79, while it was only 0.27 when there were no concerns at all. The estimates of DLD probability increased from 0.12 to 0.55 at pretest and post-test. On the other hand, the BECQ did not perform as well as the PLCQ in identifying DLD, and the improvement in diagnostic performance it provided was limited to one question.ConclusionThe parental questionnaire can be used as a screening tool to help in identifying children with DLD. The data presented in this study underscore the importance of considering linguistic parental concerns as part of the screening process. This is a realistic option to provide a solution to the current problem of underdiagnosis of DLD in Mexico.
Cost-effectiveness of Paxlovid in reducing severe COVID-19 and mortality in China
Authors: Zhang Weina , Li Lanfang , Zhou Zhen , Liu Qiao , Wang Guan , Liu Dan 
Published: June 2023

ObjectivesTo assess the cost-effectiveness of Paxlovid in reducing severe COVID-19 and its associated morality, and to investigate the affordable price of Paxlovid in China.Materials and methodsUsing a Markov model, two interventions by Paxlovid prescription (with and without prescription) were compared in terms of COVID-19-related clinical outcomes and economic loss. COVID-related costs were collected from the societal perspective. Effectiveness data were obtained from literature. The primary outcomes were total social cost, disability adjusted life-years (DALYs) and net monetary benefit (NMB). Scenario analyses were performed to investigate the affordable price of Paxlovid in China. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analysis (PSA) were performed to verify the model robustness.ResultsCompared with the non-Paxlovid cohort, the NMBs of the Paxlovid cohort were only higher in the subgroup of patients aged over 80 years old, regardless of their vaccination status. Our scenario analysis found that, the price ceiling of Paxlovid/box for it to be cost-effective was RMB 8,993 (8,970–9,009) in those aged over 80 years old who were not vaccinated, which is the highest; and was RMB 35 (27–45) in those aged 40–59 years old who were vaccinated, which is the lowest. Sensitivity analyses found that the incremental NMB for the vaccinated people aged over 80 years was most sensitive to the efficacy of Paxlovid and the cost-effectiveness probability of Paxlovid increased with its decreasing price.ConclusionUnder the current marketing price of Paxlovid/box (RMB 1,890), using Paxlovid was only cost-effective in people aged over 80 years old regardless of their vaccination status.