bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher rate of progression in HIV– than in HIV+ patients after rituximab for HHV8+ multicentric Castleman disease
Authors: Rasmussen Camille , Gérard Laurence , Fadlallah Jehane , Corvilain Emilie , Galicier Lionel , Meignin Véronique , Oksenhendler Eric , Boutboul David 
Published: June 2023

Abstract
Rituximab has revolutionized the treatment of Kaposi sarcoma–associated herpesvirus/human herpesvirus 8–associated multicentric Castleman disease (HHV8+ MCD), converting a rapidly fatal illness into a relapsing disease. HHV8+ MCD mainly affects patients with HIV infection but can also be observed in patients without HIV infection. We retrospectively analyzed a cohort of 99 patients (73 who tested HIV+ and 26 who tested HIV–), with HHV8+ MCD treated with rituximab-based therapy. Baseline characteristics were similar in patients who had HIV– and HIV+ results, although those who tested HIV– were older (65 vs 42 years) and presented less frequently with Kaposi sarcoma (15% vs 40%). Ninety-five patients (70 HIV+ and 25 HIV–) achieved complete remission (CR) after rituximab-based therapy. After a median follow-up of 51 months, 36 patients (12 HIV– and 24 HIV+) experienced disease progression. The 5-year progression-free survival (PFS) was 54%. The 5-year PFS was lower in HIV– patients than in HIV+ patients : 26% and 62%, respectively (P = .02). A multivariate prognostic factors analysis including time-dependent covariates revealed that HIV– status, reoccurrence of HHV8 DNA &gt;3 log copies per mL, and serum C-reactive protein (CRP) &gt;20 mg/mL were independently associated with an increased risk of progression after rituximab-induced CR (P = .001; P = .01; and P = .01, respectively). The lower rate of progression observed in the population with HIV+ results despite a longer follow-up period might have resulted from the possible immune restoration upon antiretroviral therapy. HHV8 viral load and serum CRP monitoring after rituximab therapy provide information on the progression risk and may help in the decision to resume specific therapy.
Efficient large-scale single-step evaluations and indirect genomic prediction of genotyped selection candidates
Authors: Vandenplas Jeremie , ten Napel Jan , Darbaghshahi Saeid Naderi , Evans Ross , Calus Mario P. L. , Veerkamp Roel , Cromie Andrew , Mäntysaari Esa A. , Strandén Ismo 
Published: June 2023

Abstract
Background
Single-step genomic best linear unbiased prediction (ssGBLUP) models allow the combination of genomic, pedigree, and phenotypic data into a single model, which is computationally challenging for large genotyped populations. In practice, genotypes of animals without their own phenotype and progeny, so-called genotyped selection candidates, can become available after genomic breeding values have been estimated by ssGBLUP. In some breeding programmes, genomic estimated breeding values (GEBV) for these animals should be known shortly after obtaining genotype information but recomputing GEBV using the full ssGBLUP takes too much time. In this study, first we compare two equivalent formulations of ssGBLUP models, i.e. one that is based on the Woodbury matrix identity applied to the inverse of the genomic relationship matrix, and one that is based on marker equations. Second, we present computationally-fast approaches to indirectly compute GEBV for genotyped selection candidates, without the need to do the full ssGBLUP evaluation.

Results
The indirect approaches use information from the latest ssGBLUP evaluation and rely on the decomposition of GEBV into its components. The two equivalent ssGBLUP models and indirect approaches were tested on a six-trait calving difficulty model using Irish dairy and beef cattle data that include 2.6 million genotyped animals of which about 500,000 were considered as genotyped selection candidates. When using the same computational approaches, the solving phase of the two equivalent ssGBLUP models showed similar requirements for memory and time per iteration. The computational differences between them were due to the preprocessing phase of the genomic information. Regarding the indirect approaches, compared to GEBV obtained from single-step evaluations including all genotypes, indirect GEBV had correlations higher than 0.99 for all traits while showing little dispersion and level bias.

Conclusions
In conclusion, ssGBLUP predictions for the genotyped selection candidates were accurately approximated using the presented indirect approaches, which are more memory efficient and computationally fast, compared to solving a full ssGBLUP evaluation. Thus, indirect approaches can be used even on a weekly basis to estimate GEBV for newly genotyped animals, while the full single-step evaluation is done only a few times within a year.
Rebounds of sevoflurane concentration during simulated trigger-free pediatric and adult anesthesia
Authors: Zumsande Simon , Thoben Christian , Dennhardt Nils , Krauß Terence , Sümpelmann Robert , Zimmermann Stefan , Rüffert Henrik , Heiderich Sebastian 
Published: June 2023

AbstractBackgroundIn trigger-free anesthesia a volatile anesthetic concentration of 5 parts per million (ppm) should not be exceeded. According to European Malignant Hyperthermia Group (EMHG) guideline, this may be achieved by removing the vapor, changing the anesthetic breathing circuit and renewing the soda lime canister followed by flushing with O2or air for a workstation specific time. Reduction of the fresh gas flow (FGF) or stand-by modes are known to cause rebound effects. In this study, simulated trigger-free pediatric and adult ventilation was carried out on test lungs including ventilation maneuvers commonly used in clinical practice. The goal of this study was to evaluate whether rebounds of sevoflurane develop during trigger-free anesthesia.MethodsA Dräger® Primus® was contaminated with decreasing concentrations of sevoflurane for 120 min. Then, the machine was prepared for trigger-free anesthesia according to EMHG guideline by changing recommended parts and flushing the breathing circuits using 10 or 18 l⋅min− 1FGF. The machine was neither switched off after preparation nor was FGF reduced. Simulated trigger-free ventilation was performed with volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) including various ventilation maneuvers like pressure support ventilation (PSV), apnea, decreased lung compliance (DLC), recruitment maneuvers, prolonged expiration and manual ventilation (MV). A high-resolution ion mobility spectrometer with gas chromatographic pre-separation was used to measure sevoflurane in the ventilation gas mixture in a 20 s interval.ResultsImmediately after start of simulated anesthesia, there was an initial peak of 11–18 ppm sevoflurane in all experiments. The concentration dropped below 5 ppm after 2–3 min during adult and 4–18 min during pediatric ventilation. Other rebounds of sevoflurane > 5 ppm occurred after apnea, DLC and PSV. MV resulted in a decrease of sevoflurane < 5 ppm within 1 min.ConclusionThis study shows that after guideline-compliant preparation for trigger-free ventilation anesthetic machines may develop rebounds of sevoflurane > 5 ppm during typical maneuvers used in clinical practice. The changes in rate and direction of internal gas flow during different ventilation modes and maneuvers are possible explanations. Therefore, manufacturers should provide machine-specific washout protocols or emphasize the use of active charcoal filters (ACF) for trigger-free anesthesia.
A randomized controlled trial of iliopsoas plane block vs. femoral nerve block for hip arthroplasty
Authors: Wang Chun-guang , Zhang Zhi-qiang , Yang Yang , Long Yu-bin , Wang Xiu-li , Ding Yan-ling 
Published: June 2023

AbstractBackgroundIliopsoas plane block (IPB) is a novel analgesic technique for hip surgery that retains quadriceps strength. However, evidence from randomized controlled trial is remains unavailable. We hypothesized that IPB, as a motor-sparing analgesic technique, could match the femoral nerve block (FNB) in pain management and morphine consumption, providing an advantage for earlier functional training in patients underwent hip arthroplasty.MethodsWe recruited ninety patients with femoral neck fracture, femoral head necrosis or hip osteoarthritis who were scheduled for unilateral primary hip arthroplasty were recruited and received either IPB or FNB. Primary outcome was the pain score during hip flexion at 4 h after surgery. Secondary outcomes included quadriceps strength and pain scores upon arrival at post anesthesia care unit (PACU) and at 2, 4, 6, 24, 48 h after surgery, the first time out of bed, total opioids consumption, patient satisfaction, and complications.ResultsThere was no significant difference in terms of pain score during hip flexion at 4 h after surgery between the IPB group and FNB group. The quadriceps strength of patients receiving IPB was superior to those receiving FNB upon arrival at PACU and at 2, 4, 6 and 24 h after surgery. The IPB group showed a shorter first time out of bed compared to the FNB group. However, there were no significant differences in terms of pain scores within 48 h after surgery, total opioids consumption, patient satisfaction and complications between the two groups.ConclusionIPB was not superior to FNB in terms of postoperative analgesia for hip arthroplasty. However, IPB could serve as an effective motor-sparing analgesic technique for hip arthroplasty, which would facilitate early recovery and rehabilitation. This makes IPB worth considering as an alternative to FNB.Trial registrationThe trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200055493; registration date: January 10, 2022; enrollment date: January 18, 2022;https://www.chictr.org.cn/searchprojEN.html).
Characterization of stemness features and construction of a stemness subtype classifier to predict survival and treatment responses in lung squamous cell carcinoma
Authors: Lai Jinzhi , Lin Xinyi , Zheng Huangna , Xie Bilan , Fu Deqiang 
Published: June 2023

Abstract
Background
Cancer stemness has been proven to affect tumorigenesis, metastasis, and drug resistance in various cancers, including lung squamous cell carcinoma (LUSC). We intended to develop a clinically applicable stemness subtype classifier that could assist physicians in predicting patient prognosis and treatment response.

Methods
This study collected RNA-seq data from TCGA and GEO databases to calculate transcriptional stemness indices (mRNAsi) using the one-class logistic regression machine learning algorithm. Unsupervised consensus clustering was conducted to identify a stemness-based classification. Immune infiltration analysis (ESTIMATE and ssGSEA algorithms) methods were used to investigate the immune infiltration status of different subtypes. Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenotype Score (IPS) were used to evaluate the immunotherapy response. The pRRophetic algorithm was used to estimate the efficiency of chemotherapeutic and targeted agents. Two machine learning algorithms (LASSO and RF) and multivariate logistic regression analysis were performed to construct a novel stemness-related classifier.

Results
We observed that patients in the high-mRNAsi group had a better prognosis than those in the low-mRNAsi group. Next, we identified 190 stemness-related differentially expressed genes (DEGs) that could categorize LUSC patients into two stemness subtypes. Patients in the stemness subtype B group with higher mRNAsi scores exhibited better overall survival (OS) than those in the stemness subtype A group. Immunotherapy prediction demonstrated that stemness subtype A has a better response to immune checkpoint inhibitors (ICIs). Furthermore, the drug response prediction indicated that stemness subtype A had a better response to chemotherapy but was more resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Finally, we constructed a nine-gene-based classifier to predict patients’ stemness subtype and validated it in independent GEO validation sets. The expression levels of these genes were also validated in clinical tumor specimens.

Conclusion
The stemness-related classifier could serve as a potential prognostic and treatment predictor and assist physicians in selecting effective treatment strategies for patients with LUSC in clinical practice.
Expression and regulatory network of E3 ubiquitin ligase NEDD4 family in cancers
Authors: Cao Liangzi , Li Hao , Liu Xiaofang , Wang Yubang , Zheng Bowen , Xing Chengzhong , Zhang Naijin , Liu Jingwei 
Published: June 2023

AbstractNEDD4 family represent an important group of E3 ligases, which regulate various cellular pathways of cell proliferation, cell junction and inflammation. Emerging evidence suggested that NEDD4 family members participate in the initiation and development of tumor. In this study, we systematically investigated the molecular alterations as well as the clinical relevance regarding NEDD4 family genes in 33 cancer types. Finally, we found that NEDD4 members showed increased expression in pancreas cancer and decreased expression in thyroid cancer. NEDD4 E3 ligase family genes had an average mutation frequency in the range of 0-32.1%, of which HECW1 and HECW2 demonstrated relatively high mutation rate. Breast cancer harbors large amount of NEDD4 copy number amplification. NEDD4 family members interacted proteins were enriched in various pathways including p53, Akt, apoptosis and autophagy, which were confirmed by further western blot and flow cytometric analysis in A549 and H1299 lung cancer cells. In addition, expression of NEDD4 family genes were associated with survival of cancer patients. Our findings provide novel insight into the effect of NEDD4 E3 ligase genes on cancer progression and treatment in the future.
Transcriptomic and functional analysis of ANGPTL4 overexpression in pancreatic cancer nominates targets that reverse chemoresistance
Authors: Gordon Emily R. , Wright Carter A. , James Mikayla , Cooper Sara J. 
Published: June 2023

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers based on five-year survival rates. Genes contributing to chemoresistance represent novel therapeutic targets that can improve treatment response. Increased expression of ANGPTL4 in tumors correlates with poor outcomes in pancreatic cancer.

Methods
We used statistical analysis of publicly available gene expression data (TCGA-PAAD) to test whether expression of ANGPTL4 and its downstream targets, ITGB4 and APOL1, were correlated with patient survival. We measured the impact of ANGPTL4 overexpression in a common pancreatic cancer cell line, MIA PaCa-2 cells, using CRISPRa for overexpression and DsiRNA for knockdown. We characterized global gene expression changes associated with high levels of ANGPTL4 and response to gemcitabine treatment using RNA-sequencing. Gemcitabine dose response curves were calculated on modified cell lines by measuring cell viability with CellTiter-Glo (Promega). Impacts on cell migration were measured using a time course scratch assay.

Results
We show that ANGPTL4 overexpression leads to in vitro resistance to gemcitabine and reduced survival times in patients. Overexpression of ANGPTL4 induces transcriptional signatures of tumor invasion and metastasis, proliferation and differentiation, and inhibition of apoptosis. Analyses revealed an overlapping signature of genes associated with both ANGPTL4 activation and gemcitabine response. Increased expression of the genes in this signature in patient PDAC tissues was significantly associated with shorter patient survival. We identified 42 genes that were both co-regulated with ANGPTL4 and were responsive to gemcitabine treatment. ITGB4 and APOL1 were among these genes. Knockdown of either of these genes in cell lines overexpressing ANGPTL4 reversed the observed gemcitabine resistance and inhibited cellular migration associated with epithelial to mesenchymal transition (EMT) and ANGPTL4 overexpression.

Conclusions
These data suggest that ANGPTL4 promotes EMT and regulates the genes APOL1 and ITGB4. Importantly, we show that inhibition of both targets reverses chemoresistance and decreases migratory potential. Our findings have revealed a novel pathway regulating tumor response to treatment and suggest relevant therapeutic targets in pancreatic cancer.
The relationship between pepsinogen C and gastric carcinogenesis: a transgene and population study
Authors: E. Ying , Yu Qian , Sun Tao , Xue Hang , Zhao Xue-rong , Zheng Hua-chuan 
Published: June 2023

Abstract
Background
Pepsinogen C (PGC) is expressed in chief cells, fundic mucous neck cells, and pyloric gland cells of gastric epithelium and also in breast, prostate, lung, and seminal vesicles.

Methods
We explored the clinicopathological and prognostic significances of PGC mRNA using pathological and bioinformatics analyses. We generated PGC knockout and PGC-cre transgenic mice to observe the effects of PGC deletion and PTEN abrogation in PGC-positive cells on gastric carcinogenesis. Finally, we observed the effects of altered PGC expression on aggressive phenotypes by CCK8, Annexin V staining, wound healing and transwell assays and analyzed the partner proteins of PGC using co-IP (co-immunoprecipitation) and double fluorescence staining.

Results
PGC mRNA level was inversely correlated with the T and G stage and a short survival of gastric cancer (p < 0.05). PGC protein expression was negatively linked to lymph node metastasis, dedifferentiation, and low Her-2 expression of gastric cancer (p < 0.05). No difference in body weight or length was evident between wild-type (WT) and PGC knockout (KO) mice (p > 0.05), but PGC KO mice had a shorter survival than WT mice (p < 0.05). No gastric lesions were observed in the mucosa of the granular stomach in PGC KO mice, which displayed lower frequency and severity of gastric lesion than in WT mice after treated with MNU. Transgenic PGC-cre mice showed high cre expression and activity in the lung, stomach, kidney, and breast. Gastric cancer and triple-negative lobular breast adenocarcinoma were found in PGC-cre/PTENf/f mice with two previous pregnancies and breast feeding, but breast cancer was not seen in transgenic mice exposed to either estrogen or progesterone, or those with two previous pregnancies and no breast feeding. PGC suppressed proliferation, migration, invasion, and induced apoptosis, and interacted with CCNT1, CNDP2 and CTSB.

Conclusion
PGC downregulation was seen in gastric cancer, but PGC deletion resulted in resistance to chemically-induced gastric carcinogenesis. PGC expression suppressed the proliferation and invasion of gastric cancer cells possibly by interacting with CCNT1, CNDP2 and CTSB. Spontaneous triple-negative lobular adenocarcinoma and gastric cancer were seen in PGC-cre/PTENf/f mice, and the breast carcinogenesis was closely linked to pregnancy and breast feeding, but not to single exposure to estrogen or progesterone, or pregnancy. Limiting either pregnancy or breast feeding might help to prevent hereditary breast cancer.
Temporal reciprocal relationships among anxiety, depression, and posttraumatic stress disorder for family surrogates from intensive care units over their first two bereavement years
Authors: Wen Fur-Hsing , Juang Yeong-Yuh , Prigerson Holly G. , Chou Wen-Chi , Huang Chung-Chi , Hu Tsung-Hui , Chiang Ming Chu , Chuang Li-Pang , Tang Siew Tzuh 
Published: June 2023

Abstract
Background/Objective
Bereaved family surrogates from intensive care units (ICU) are at risk of comorbid anxiety, depression, and post-traumatic stress disorder (PTSD), but the temporal reciprocal relationships among them have only been examined once among veterans. This study aimed to longitudinally investigate these never-before-examined temporal reciprocal relationships for ICU family members over their first two bereavement years.

Methods
In this prospective, longitudinal, observational study, symptoms of anxiety, depression, and PTSD were assessed among 321 family surrogates of ICU decedents from 2 academically affiliated hospitals in Taiwan by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale, and the Impact of Event Scale-Revised, respectively at 1, 3, 6, 13, 18, and 24 months postloss. Cross-lagged panel modeling was conducted to longitudinally examine the temporal reciprocal relationships among anxiety, depression, and PTSD.

Results
Examined psychological-distress levels were markedly stable over the first 2 bereavement years: autoregressive coefficients for symptoms of anxiety, depression, and PTSD were 0.585–0.770, 0.546–0.780, and 0.440–0.780, respectively. Cross-lag coefficients showed depressive symptoms predicted PTSD symptoms in the first bereavement year, whereas PTSD symptoms predicted depressive symptoms in the second bereavement year. Anxiety symptoms predicted symptoms of depression and PTSD at 13 and 24 months postloss, whereas depressive symptoms predicted anxiety symptoms at 3 and 6 months postloss while PTSD symptoms predicted anxiety symptoms during the second bereavement year.

Conclusions
Different patterns of temporal relationships among symptoms of anxiety, depression, and PTSD over the first 2 bereavement years present important opportunities to target symptoms of specific psychological distress at different points during bereavement to prevent the onset, exacerbation, or maintenance of subsequent psychological distress.
Constructing an emergency preparedness evaluation index system for public use during major emerging infectious disease outbreaks: a Delphi study
Authors: Wei Wei , Liu Yubei , Zhou Na , Tian Min , Xie Longsheng , Watson Roger , Dai Fengling , Chen Yanhua , Hu Weili 
Published: June 2023

Abstract
Background
The major emerging infectious diseases (MEIDs) have occurred frequently and become increasingly serious in the world. Sufficient personal emergency preparedness is critical for the general people in efficiently responding to and recovering from MEIDs. Nevertheless, few specific indicators are available for assessing the individual emergency preparedness of the general public during these periods. Therefore, the aim of this study was to construct an index system for comprehensively evaluating the personal emergency preparedness of the public regarding MEIDs.

Methods
Based on the global national-level emergency preparedness index framework and a literature review, a preliminary index system was constructed. From June 2022 to September 2022, a panel of 20 experts from nine provinces and municipalities across multiple research areas participated in this Delphi study. They rated the importance of pre-defined indicators using a five-point Likert scale and provided their qualitative comments. According to the feedback of each round of experts, the indicators of the evaluation index system were revised.

Results
After two rounds of expert consultation the evaluation index system reached a consensus, containing five first-level indicators, cooperating with prevention and control work, improving emergency response capacity, securing supplies and equipment, preparing economic resources, maintaining physical and mental health with affiliated 20 s-level indicators and 53 third-level indicators. The expert authority coefficient of consultation was 0.88 and 0.90. The Kendall’s coefficient of concordance of expert consultations was 0.294 and 0.322, respectively. The differences were statistically significant (P < 0.05).

Conclusion
A valid, reliable and scientific evaluation index system was established. This personal emergency preparedness index system, as a precursor form, will further lay the foundation for the formation of an assessment instrument. At the same time, it could provide a reference for future education and training of emergency preparedness for the general public.