bluuebunny/crossref_metadata_2025_split huggingface dataset:
Definition of a new blood cell count score for early survival prediction for non-small cell lung cancer patients treated with atezolizumab: Integrated analysis of four multicenter clinical trials
Authors: Zhou Jian-Guo , Wong Ada Hang-Heng , Wang Haitao , Jin Su-Han , Tan Fangya , Chen Yu-Zhong , He Si-Si , Shen Gang , Frey Benjamin , Fietkau Rainer , Hecht Markus , Carr Shamus R. , Wang Ruihong , Shen Bo , Schrump David S. , Ma Hu , Gaipl Udo S. 
Published: September 2022

ImportanceBlood cell count test (BCT) is a robust method that provides direct quantification of various types of immune cells to reveal the immune landscape to predict atezolizumab treatment outcomes for clinicians to decide the next phase of treatment.ObjectiveThis study aims to define a new BCTscore model to predict atezolizumab treatment benefits in non-small lung cell cancer (NSCLC) patients.Design, Setting, and ParticipantsThis study analyzed four international, multicenter clinical trials (OAK, BIRCH, POPLAR, and FIR trials) to conduct post-hoc analyses of NSCLC patients undergoing atezolizumab (anti–PD-L1) single-agent treatment (n = 1,479) or docetaxel single-agent treatment (n = 707). BCT was conducted at three time points: pre-treatment (T1), the first day of treatment cycle 3 (T2), and first day of treatment cycle 5 (T3). Univariate and multivariate Cox regression analyses were conducted to identify early BCT biomarkers to predict atezolizumab treatment outcomes in NSCLC patients.Main Outcomes and MeasuresOverall survival (OS) was used as the primary end point, whereas progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST), clinical benefit (CB), and objective response rate (ORR) were used as secondary end points.ResultsThe BCT biomarkers of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at time point T3 and neutrophil-to-monocyte ratio (NMR) at time point T2 with absolute cutoff values of NLR_T3 = 5, PLR_T3 = 180, and NMR_T2 = 6 were identified as strong predictive biomarkers for atezolizumab (Ate)–treated NSCLC patients in comparison with docetaxel (Dtx)–treated patients regarding OS (BCTscore low risk: HR Ate vs. Dtx = 1.54 (95% CI: 1.04–2.27), P = 0.031; high risk: HR Ate vs. Dtx = 0.84 (95% CI: 0.62–1.12), P = 0.235). The identified BCTscore model showed better OS AUC in the OAK (AUC12month = 0.696), BIRCH (AUC12month = 0.672) and POPLAR+FIR studies (AUC12month = 0.727) than that of each of the three single BCT biomarkers.Conclusion and RelevanceThe BCTscore model is a valid predictive and prognostic biomarker for early survival prediction in atezolizumab-treated NSCLC patients.
“There and back again” - Ultrastructural changes in the gills of Bathymodiolus vent-mussels during symbiont loss: Back to a regular filter-feeding epidermis
Authors: Piquet Bérénice , Le Panse Sophie , Lallier François H. , Duperron Sébastien , Andersen Ann C. 
Published: September 2022

Deep-sea mussels Bathymodiolus azoricus, from Azorean hydrothermal vents, house two types of symbionts in their fleshy gills: methane-oxidizing (MOX) and sulfide-oxidizing (SOX) Gamma-proteobacteria. As soon as the mussels are collected, their symbionts are deprived from their environmental nutrient flux, and cannot rely on their usual metabolism. Recent studies have shown that the gill cells undergo high rates of apoptosis, as well as regionalized cell proliferation. This study follows the fate of the symbionts and of the hosting bacteriocytes at the ultrastructural level, during an extended starvation period. Just upon collection, we evidenced an apico-basal journey of the symbionts in the bacteriocytes, starting with (1) apical single symbiont endocytosis, (2) symbiont division, (3) symbiont storage, (4) and symbiont digestion within lysosomes, above the basal lamina. After 4-9 days starvation, endocytosis occurred with (5) empty blebbing, (6) the lysosomes increased in size, and the bacteriocytes lost their apical membrane, resulting in (7) a baso-apical return of the symbiont-containing lysosomes outside the gills, while the nucleus showed condensed chromatin, characteristic of apoptosis/necroptosis (8). Between the bacteriocytes, narrow intercalary cells appear to divide (9). Our hypothesis is that intercalary cells are stem cells that replace lost bacteriocytes. After 61 days there was no symbiont left, and the epidermis resembled those of the non-symbiotic filter-feeding mussel Mytilus edulis.
Seroprevalence and burden of hepatitis E viral infection among pregnant women in central Nigeria attending antenatal clinic at a Federal Medical Centre in Central Nigeria
Authors: Ehi Airiohuodion Philomena , Wartel Anh , Yako Andrew B. , Mac Peter Asaga 
Published: September 2022

IntroductionHEV infection may be life threatening in pregnant women and has been linked with 20–30% mortality, especially in the third trimester of pregnancy. HEV infection leads to elevated levels of preterm labour and other immunological parameters. It is vertically transmitted and could lead to poor feto-maternal outcomes. especially in fulminating viral hepatitis where both the mother and foetus could be lost. There is currently no known treatment or vaccine for HEV. There is therefore a need to study HEV seroprevalence and burden among vulnerable groups, such as pregnant women and their newborns in Nigeria, where maternal mortality is highly significant.MethodsA total of 200 samples were collected from pregnant women attending antenatal clinic at Federal Medical Centre (FMC) Keffi, in central Nigeria, of which (156/200) samples were from HIV-negative pregnant women and (44/200) were from HIV-positive pregnant women, using a simple random sampling method.ResultsIn total, 200 pregnant women [78.0% (156/200) HIV-negative pregnant women and 22.0% (44/200) HIV-positive pregnant women] were recruited for this study. The ages of the pregnant women ranged from 15-49 years, with a mean age of 26.4 years (± 6.23). The overall HEV IgG seropositivity in the study population was 31.5% (63/200); 95% CI (30-33).ConclusionThis study highlighted an unexpectedly high seroprevalence of HEV and poor feto-maternal outcomes in pregnant women residing in a rural and urban setting of central Nigeria. The study showed that the inherently high HEV seropositivity and poor feto-maternal outcomes may not be attributed to HEV viral hepatitis only but may be a combination of extrinsic and intrinsic factors.
Sentinel Lymph Node Biopsy in Prostate Cancer Patients: Results From an Injection Technique Targeting the Index Lesion in the Prostate Gland
Authors: Fumadó Lluís , Abascal Jose M. , Mestre-Fusco Antoni , Vidal-Sicart Sergi , Aguilar Guadalupe , Juanpere Nuria , Cecchini Lluís 
Published: September 2022

ObjectivesTo determine the accuracy of nodal staging in patients with prostate cancer (PCa) when 99mTc-nanocolloid radiotracer is injected into an index lesion (IL).MethodsThis prospective study was conducted at our institution between June 2016 and October 2020. It included 64 patients with localized PCa with at least a 5% possibility for lymph node involvement in the Memorial Sloan Kettering Cancer Center nomogram, suitable for surgical treatment. All patients underwent magnetic resonance imaging (MRI) with IL and were pathologically confirmed. The day before surgery, transrectal ultrasound-guided injection (TRUS) of 99mTc-nanocolloid into the IL was performed. Surgical procedures included radical prostatectomy (RP), sentinel lymph node biopsy (SLNB), and extended pelvic lymphadenectomy (ePLND). Analysis was performed, including histopathological findings of RP, ePLND, and SLNB. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), false negative (FN), false positive (FP), diagnostic yield, and non-diagnostic rate were calculated.ResultsA total of 1,316 lymph nodes were excised, including 1,102 from the ePLND (83.7%) and 214 (16.3%) sentinel lymph nodes (SLN). 26 SLN were dissected outside the ePLND template. The final pathology demonstrated 46 (3.5%) lymph node metastasis, 31 (67.4%) in the SLNB and 15 (32.6%) in the non-SLN ePLND. At the patient level, 18 (28.1%) patients had pN1. With a mean follow-up of 33.1 months, 4/19 (21.1%) pN1 patients had undetectable PSA, and 3/19 (15.8%) had a PSA &lt; 0.1 ng/mL. Lymph node dissection included 20.6 lymph nodes per patient (IQR 15–24.2), with 3.3 SLNB nodes per patient (IQR 2–4.2). PPV and NPV were 100 and 97.8%, respectively. Sensitivity and specificity were 94.4 and 100%, respectively. FN was 5.5% and FP was 4.3%. Diagnostic yields were 95.3% and the non-diagnostic rate was 4.7%.ConclusionRadiotracer injection into the prostate IL offers promising results for staging purposes in cases in which ePLND is considered. Negative SLNB is a predictor of negative ePLND. Patients with a limited burden of nodal metastasis have a significant chance of remaining free of biochemical recurrence at mid-term follow-up.
Moderate sedation by total intravenous remimazolam-alfentanil vs. propofol-alfentanil for third molar extraction: A prospective randomized controlled trial
Authors: Zhao Nan , Zeng Jie , Fan Lin , Wang Jing , Zhang Chao , Zou SiHai , Zhang Bi , Li Kai , Yu Cong 
Published: September 2022

BackgroundOral dental treatment cause anxiety, fear, and physical stress. This study aimed to investigate the efficacy and safety of moderate sedation by remimazolam with alfentanil vs. propofol with alfentanil in third molar extraction.MethodsThis single-center, randomized, single-blind clinical trial included 100 adults who underwent third molar ambulatory extraction. All patients had continuous infusion of Alfentanil 0.2 μg/kg/min. Group remimazolam with alfentanil (group RA) had an induction dose of 80 μg/kg and maintenance dosage of 5 μg/kg/min. In group propofol with alfentanil (PA group), propofol was infused at an initial concentration of 1.8 μg/mL under target controlled infusion (TCI) mode and a maintenance concentration of 1.5 μg/mL. The incidence rates of adverse effects were recorded and compared. Depth of sedation was assessed using the modified observer alertness/sedation assessment (MOAA/S) and entropy index. Recovery characteristics were recorded and complications observed for next 24 h.ResultsThe incident of adverse events 6 (12%) in the group RA was lower than the group PA 25 (50%) [Mean difference 0.136 (95%CI, 0.049–0.377); P &lt; 0.05], with no serious adverse events during the sedation procedure. The incidence of injection pain in group RA was significantly lower than that in group PA [4 vs. 26%, mean difference 0.119 (95%CI, 0.025–0.558); P = 0.004]. Before starting local anesthesia, the mean arterial pressure, heart rate, and respiratory rate of the PA group were lower than those of the RA group. None of the patients required further treatments for a decreased heart rate, blood pressure, or low SpO2. The rate of moderate sedation success was 100% in both groups. The MOAA/S score was similar between the groups indicating that the depth of sedation was effective. Group RA had significantly shorter recovery and discharge times than those of group PA.ConclusionsRemimazolam with alfentanil is a safer and more effective alternative for ambulatory sedation and can reduce recovery and discharge time and the incidence of perioperative adverse events compare with propofol.Clinical trial registrationhttp://www.chictr.org.cn/index.aspx, identifier: ChiCTR2200058106.
Switching from one biologic to benralizumab in patients with severe eosinophilic asthma: An ANANKE study post hoc analysis
Authors: Caruso Cristiano , Cameli Paolo , Altieri Elena , Aliani Maria , Bracciale Pietro , Brussino Luisa , Caiaffa Maria Filomena , Canonica Giorgio Walter , Centanni Stefano , D’Amato Maria , Del Giacco Stefano , De Michele Fausto , Pastorello Elide Anna , Pelaia Girolamo , Rogliani Paola , Romagnoli Micaela , Schino Pietro , Caminati Marco , Vultaggio Alessandra , Zullo Alessandro , Rizzoli Sara , Boarino Silvia , Vitiello Gianfranco , Menzella Francesco , Di Marco Fabiano 
Published: September 2022

BackgroundSevere asthma is a heterogeneous inflammatory disease driven by eosinophilic inflammation in the majority of cases. Despite biologic therapy patients may still be sub-optimally controlled, and the choice of the best biologic is a matter of debate. Indeed, switching between biologics is common, but no official guidelines are available and real-world data are limited.Materials and methodsIn this post hoc analysis of the Italian, multi-center, observational, retrospective study, ANANKE. Patients with severe eosinophilic asthma treated with benralizumab were divided in two groups based on history of previous biologic therapy (biologic-experienced [suboptimal response] vs naïve). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment. Change over time in blood eosinophils, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use following benralizumab initiation were collected in the two groups.ResultsA total of 147 biologic-naïve and 58 biologic-experienced (34 omalizumab, 19 mepolizumab, and 5 omalizumab-mepolizumab) patients were enrolled. Biologic-experienced patients were more likely to be atopic and have a higher AER despite more frequent OCS use. Similar reductions in AER (&gt;90% in both groups), OCS use (≥49% reduction in dosage and ≥41% able to eliminate OCS), ACT improvement (≥7 points gained in 48 weeks) and lung function (≥300 mL of FEV1 improvement in 48 weeks) were observed after benralizumab introduction within the two groups. There were no registered discontinuations of benralizumab for safety reasons.ConclusionIn this post hoc analysis, patients who were switched to benralizumab because of suboptimal control with a previous biologic therapy were more likely to be atopic and more often treated with omalizumab. Benralizumab is effective in both naïve patients and those previously treated with a biologic.
Epidemiology, prevalence, and associated factors of oral candidiasis in HIV patients from southwest Iran in post-highly active antiretroviral therapy era
Authors: Erfaninejad Maryam , Zarei Mahmoudabadi Ali , Maraghi Elham , Hashemzadeh Mohammad , Fatahinia Mahnaz 
Published: September 2022

BackgroundOral candidiasis (OC) is one of the most common opportunistic fungal infections among people living with HIV/AIDS (PLWHA). The prevalence of OC and Candida profiles among HIV-infected patients might be changing in the era of Highly Active Antiretroviral Therapy (HAART). This study aimed to identify Candida spp., determine OC prevalence and associated risk factors for PLWHA.Materials and methodsOral candidiasis prevalence was explored in oral swabs of 276 patients who referred for consultation at Behavioral Diseases Counseling Center (BDCC). Clinical symptoms, culture and molecular assays were used for OC detection. In statistical analysis, we assessed socio-demographic characteristics, clinical information and treatment history of some infections.ResultsThe overall prevalence of OC was 41%. Candida albicans (64.6%) was the most common species, followed by C. glabrata (26.5%) and C. dubliniensis (19.5%). Candida famata, C. africana, and C. stellatoidea as the first fungi isolated from OC in PLWHA from southwest Iran. In 36.3% of patients, mixed cultures of more than one species were observed. Body mass index (BMI) (OR = 0.947; CI = 0.89–0.99; p = 0.045) and CD4 count ≤ 200 cells/mm3 (OR = 4.365; CI = 1.73–10.98; p = 0.002) were the predictors of OC in the final model of multiple logistic regression analysis. Education level, addiction status, sexual behaviors, chest X-ray, other infections and WHO clinical stage were other important risk factors for OC.ConclusionOral candidiasis remains a significant opportunistic infection in post-HAART era among PLWHA. Despite the increasing prevalence of NAC species, C. albicans (64.6%) was still the predominant species. Our results showed that low BMI with OC indicates treatment failure (i.e., failure to increase CD4 count or suppress viral load). Also, low CD4 counts (≤200 cells/mm3) in HIV patients show an impaired immune status, and our findings emphasize that OC can be a clinical indicator of HIV infection in individuals who do not know their HIV status or have failed treatment.
Construction of an endoplasmic reticulum stress-related gene model for predicting prognosis and immune features in kidney renal clear cell carcinoma
Authors: Shen Yuanhao , Cao Yinghao , Zhou Lei , Wu Jianfeng , Mao Min 
Published: September 2022

Background: Kidney renal clear cell carcinoma (KIRC) is one of the most lethal malignant tumors with a propensity for poor prognosis and difficult treatment. Endoplasmic reticulum (ER) stress served as a pivotal role in the progression of the tumor. However, the implications of ER stress on the clinical outcome and immune features of KIRC patients still need elucidation.Methods: We identified differentially expressed ER stress-related genes between KIRC specimens and normal specimens with TCGA dataset. Then, we explored the biological function and genetic mutation of ER stress-related differentially expressed genes (DEGs) by multiple bioinformatics analysis. Subsequently, LASSO analysis and univariate Cox regression analysis were applied to construct a novel prognostic model based on ER stress-related DEGs. Next, we confirmed the predictive performance of this model with the GEO dataset and explored the potential biological functions by functional enrichment analysis. Finally, KIRC patients stratified by the prognostic model were assessed for tumor microenvironment (TME), immune infiltration, and immune checkpoints through single-sample Gene Set Enrichment Analysis (ssGSEA) and ESTIMATE analysis.Results: We constructed a novel prognostic model, including eight ER stress-related DEGs, which could stratify two risk groups in KIRC. The prognostic model and a model-based nomogram could accurately predict the prognosis of KIRC patients. Functional enrichment analysis indicated several biological functions related to the progression of KIRC. The high-risk group showed higher levels of tumor infiltration by immune cells and higher immune scores.Conclusion: In this study, we constructed a novel prognostic model based on eight ER stress-related genes for KIRC patients, which would help predict the prognosis of KIRC and provide a new orientation to further research studies on personalized immunotherapy in KIRC.
Divergent patterns of cognitive deficits and structural brain alterations between older adults in mixed-sex and same-sex relationships
Authors: Manca Riccardo , Correro Anthony N. , Gauthreaux Kathryn , Flatt Jason D. 
Published: September 2022

BackgroundSexual minority (SM) older adults experience mental health disparities. Psychiatric disorders and neuropsychiatric symptoms (NPS) are risk factors for cognitive decline. Although older people in same-sex (SSR) compared to mixed-sex relationships (MSR) perform more poorly on cognitive screening tests, prior studies found no differences in rates of dementia diagnosis or neuropsychological profiles. We sought to explore the role of NPS on neurocognitive outcomes for SM populations. We compared cognitive performance and structural brain parameters of older adults in SSR and MSR.MethodsData were originally collected at Alzheimer's Disease Research Centers (ADRCs). Inclusion criteria were: age of 55+ years, a study partner identified as a spouse/partner, and availability of T1-MRI brain volumes/thickness. Participants were labeled as either SSR or MSR based on their/their co-participant's reported sex. We identified 1,073 participants (1,037 MSR−555 cognitively unimpaired [CU]; 36 SSR−23 CU) with structural MRI data, Mini-Mental State Exam (MMSE), and Neuropsychiatric Inventory Questionnaire (NPI-Q) scores. A subset of the overall sample completed comprehensive neuropsychological assessment (n = 939; 908 MSR−494 CU; 31 SSR−22 CU). Covariates included in statistical models were age, sex, education, total intracranial volume, and apolipoprotein E genotype.ResultsMultivariate general linear models showed significant diagnosis-by-relationship interaction effects on the left parahippocampal gyrus volume. After stratification by relationship group, only cognitively impaired (CI) MSR had significantly smaller left parahippocampal volumes than MSR-CU. The SSR group showed better episodic memory performance. Severity of neuropsychiatric symptoms was negatively associated with volume/thickness of bilateral fronto-temporal areas and with MMSE scores, predominantly in the MSR group.ConclusionIn our study, MSR participants presented with a more compromised cognitive profile than SSR participants. MSR-CI participants showed significantly smaller left medio-temporal volumes, a neural signature of AD. Neuropsychiatric symptoms predicted smaller fronto-temporal volumes in the MSR more consistently than in the SSR group. These findings may be due to unexplored protective factors against cognitive decline in SM elders. Indeed, social support has been proposed as a protective factor warranting future investigation.
Longitudinal monitoring of amyotrophic lateral sclerosis by diffusion tensor imaging: Power calculations for group studies
Authors: Behler Anna , Lulé Dorothée , Ludolph Albert C. , Kassubek Jan , Müller Hans-Peter 
Published: September 2022

IntroductionDiffusion tensor imaging (DTI) can be used to map disease progression in amyotrophic lateral sclerosis (ALS) and therefore is a promising candidate for a biomarker in ALS. To this end, longitudinal study protocols need to be optimized and validated regarding group sizes and time intervals between visits. The objective of this study was to assess the influences of sample size, the schedule of follow-up measurements, and measurement uncertainties on the statistical power to optimize longitudinal DTI study protocols in ALS.Patients and methodsTo estimate the measurement uncertainty of a tract-of–interest-based DTI approach, longitudinal test-retest measurements were applied first to a normal data set. Then, DTI data sets of 80 patients with ALS and 50 healthy participants were analyzed in the simulation of longitudinal trajectories, that is, longitudinal fractional anisotropy (FA) values for follow-up sessions were simulated for synthetic patient and control groups with different rates of FA decrease in the corticospinal tract. Monte Carlo simulations of synthetic longitudinal study groups were used to estimate the statistical power and thus the potentially needed sample sizes for a various number of scans at one visit, different time intervals between baseline and follow-up measurements, and measurement uncertainties.ResultsFrom the simulation for different longitudinal FA decrease rates, it was found that two scans per session increased the statistical power in the investigated settings unless sample sizes were sufficiently large and time intervals were appropriately long. The positive effect of a second scan per session on the statistical power was particularly pronounced for FA values with high measurement uncertainty, for which the third scan per session increased the statistical power even further.ConclusionWith more than one scan per session, the statistical power of longitudinal DTI studies can be increased in patients with ALS. Consequently, sufficient statistical power can be achieved even with limited sample sizes. An improved longitudinal DTI study protocol contributes to the detection of small changes in diffusion metrics and thereby supports DTI as an applicable and reliable non-invasive biomarker in ALS.