bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retained avidity despite reduced cross-binding and cross-neutralizing antibody levels to Omicron after SARS-COV-2 wild-type infection or mRNA double vaccination
Authors: Harthaller Teresa , Falkensammer Barbara , Bante David , Huber Maria , Schmitt Melanie , Benainouna Habib , Rössler Annika , Fleischer Verena , von Laer Dorothee , Kimpel Janine , Würzner Reinhard , Borena Wegene 
Published: July 2023

IntroductionThe rapid evolution of SARS-CoV-2 has posed a challenge to long-lasting immunity against the novel virus. Apart from neutralizing function, binding antibodies induced by vaccination or infection play an important role in containing the infection. MethodsTo determine the proportion of wild-type (WT)–generated antibodies recognizant of more recent variants, plasma samples from either SARS-CoV-2 WT-infected (n = 336) or double-mRNA (Comirnaty)–vaccinated individuals (n = 354, age and sex matched to the convalescent group) were analyzed for binding antibody capacity against the S1 protein of the BA.1 omicron variant. ResultsOverall, 38.59% (95% CI, 37.01– 40.20) of WT-generated antibodies recognized Omicron BA.1 S1 protein [28.83% (95% CI, 26.73–30.91) after infection and 43.46% (95% CI, 41.61–45.31) after vaccination; p &lt; 0.001]. Although the proportion of WT-generated binding and neutralizing antibodies also binding to BA.1 is substantially reduced, the avidity of the remaining antibodies against the Omicron variant was non-inferior to that of the ancestral virus: Omicron: 39.7% (95% CI: 38.1–41.3) as compared to the avidity to WT: 27.0% (95% CI, 25.5–28.4), respectively (p &lt; 0.001). Furthermore, we noticed a modestly yet statistically significant higher avidity toward the Omicron epitopes among the vaccinated group (42.2%; 95% CI, 40.51–43.94) as compared to the convalescent counterparts (36.4%; 95% CI, 33.42–38.76) (p = 0.003), even after adjusting for antibody concentration. DiscussionOur results suggest that an aspect of functional immunity against the novel strain was considerably retained after WT contact, speculatively counteracting the impact of immune evasion toward neutralization of the strain. Higher antibody levels and cross-binding capacity among vaccinated individuals suggest an advantage of repeated exposure in generating robust immunity.
Prognostic nutritional index as a prognostic biomarker for gastrointestinal cancer patients treated with immune checkpoint inhibitors
Authors: Zhang Lilong , Ma Wangbin , Qiu Zhendong , Kuang Tianrui , Wang Kunpeng , Hu Baohong , Wang Weixing 
Published: July 2023

ObjectiveOur study represents the first meta-analysis conducted to evaluate the prognostic utility of the baseline prognostic nutritional index (PNI) in patients with gastrointestinal cancer (GIC) who received immune checkpoint inhibitor (ICI) therapy.MethodsWe searched PubMed, the Cochrane Library, EMBASE, and Google Scholar until April 23, 2023, to obtain relevant articles for this study. Our analysis examined several clinical outcomes, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).ResultsIn this analysis, a total of 17 articles with 2883 patients were included. Our pooled results indicated that patients with high PNI levels had longer OS (HR: 0.530, 95% CI: 0.456-0.616, p &lt; 0.001) and PFS (HR: 0.740, 95% CI: 0.649-0.844, p &lt; 0.001), as well as higher ORR (OR: 1.622, 95% CI: 1.251-2.103, p &lt; 0.004) and DCR (OR: 1.846, 95% CI: 1.428-2.388, p &lt; 0.001). Subgroup analysis showed that PNI cutoff values of 40 to 45 showed greater predictive potential. Subgroup analysis also confirmed that the above findings still hold true in patients with esophageal cancer, gastric cancer, and hepatocellular carcinomas.ConclusionThe PNI were reliable predictors of outcomes in GIC patients treated with ICIs.
Subthalamic deep brain stimulation for primary dystonia: defining an optimal location using the medial subthalamic nucleus border as anatomical reference
Authors: Zhao Mingming , Chen Hui , Yan Xin , Li Jianguang , Lu Chao , Cui Bin , Huo Wenjun , Cao Shouming , Guo Hui , Liu Shuang , Yang Chunjuan , Liu Ying , Yin Feng 
Published: July 2023

IntroductionAlthough the subthalamic nucleus (STN) has proven to be a safe and effective target for deep brain stimulation (DBS) in the treatment of primary dystonia, the rates of individual improvement vary considerably. On the premise of selecting appropriate patients, the location of the stimulation contacts in the dorsolateral sensorimotor area of the STN may be an important factor affecting therapeutic effects, but the optimal location remains unclear. This study aimed to define an optimal location using the medial subthalamic nucleus border as an anatomical reference and to explore the influence of the location of active contacts on outcomes and programming strategies in a series of patients with primary dystonia.MethodsData from 18 patients who underwent bilateral STN-DBS were retrospectively acquired and analyzed. Patients were assessed preoperatively and postoperatively (1 month, 3 months, 6 months, 1 year, 2 years, and last follow-up after neurostimulator initiation) using the Toronto Western Spasmodic Torticollis Rating Scale (for cervical dystonia) and the Burke–Fahn–Marsden Dystonia Rating Scale (for other types). Optimal parameters and active contact locations were determined during clinical follow-up. The position of the active contacts relative to the medial STN border was determined using postoperative stereotactic MRI.ResultsThe clinical improvement showed a significant negative correlation with the y-axis position (anterior–posterior; A+, P−). The more posterior the electrode contacts were positioned in the dorsolateral sensorimotor area of the STN, the better the therapeutic effects. Cluster analysis of the improvement rates delineated optimal and sub-optimal groups. The optimal contact coordinates from the optimal group were 2.56 mm lateral, 0.15 mm anterior, and 1.34 mm superior relative to the medial STN border.ConclusionSTN-DBS was effective for primary dystonia, but outcomes were dependent on the active contact location. Bilateral stimulation contacts located behind or adjacent to Bejjani’s line were most likely to produce ideal therapeutic effects. These findings may help guide STN-DBS preoperative planning, stimulation programming, and prognosis for optimal therapeutic efficacy in primary dystonia.
A longitudinal investigation of pragmatic language across contexts in autism and related neurodevelopmental conditions
Authors: Martin Gary E. , Lee Michelle , Bicknell Klinton , Goodkind Adam , Maltman Nell , Losh Molly 
Published: July 2023

BackgroundPragmatic language, or the use of language in social contexts, is a critical skill in daily life, supporting social interactions and the development of meaningful social relationships. Pragmatic language is universally impacted in autism spectrum disorder (ASD) and pragmatic deficits are also common in other neurodevelopmental conditions, particularly those related to ASD, such as fragile X syndrome (FXS). This study used a multi-method, longitudinal approach to characterize potentially unique pragmatic profiles across different neurodevelopmental disabilities, and across contexts that varied in degree of social demand. The utility of computational linguistic analyses, as an efficient tool for capturing pragmatic abilities, was also explored.MethodsPragmatic skills of boys with idiopathic ASD (ASD-O, n = 43), FXS with and without ASD (FXS-ASD, n = 57; FXS-O, n = 14), Down syndrome (DS, n = 22), and typical development (TD, n = 24) were compared using variables obtained from a standardized measure, narrative, and semi-naturalistic conversation at up to three time points.ResultsPragmatic language was most significantly impacted among males with ASD-O and FXS-ASD across all three contexts, with more difficulties in the least structured context (conversation), and also some differences based on FXS comorbidity. Patterns of group differences were more nuanced for boys with FXS-O and DS, with context having less of an impact. Clinical groups demonstrated minimal changes in pragmatic skills with age, with some exceptions. Computational language measurement tools showed some utility for measuring pragmatic skills, but were not as successful as traditional methods at capturing differences between clinical groups.ConclusionOverlap and differences between ASD and other forms of neurodevelopmental disability in general, and between idiopathic and syndromic ASD in particular, have important implications for developing precisely tailored assessment and intervention approaches, consistent with a personalized medicine approach to clinical study and care in ASD.
Generalization optimizing machine learning to improve CT scan radiomics and assess immune checkpoint inhibitors’ response in non-small cell lung cancer: a multicenter cohort study
Authors: Tonneau Marion , Phan Kim , Manem Venkata S. K. , Low-Kam Cecile , Dutil Francis , Kazandjian Suzanne , Vanderweyen Davy , Panasci Justin , Malo Julie , Coulombe François , Gagné Andréanne , Elkrief Arielle , Belkaïd Wiam , Di Jorio Lisa , Orain Michele , Bouchard Nicole , Muanza Thierry , Rybicki Frank J. , Kafi Kam , Huntsman David , Joubert Philippe , Chandelier Florent , Routy Bertrand 
Published: July 2023

BackgroundRecent developments in artificial intelligence suggest that radiomics may represent a promising non-invasive biomarker to predict response to immune checkpoint inhibitors (ICIs). Nevertheless, validation of radiomics algorithms in independent cohorts remains a challenge due to variations in image acquisition and reconstruction. Using radiomics, we investigated the importance of scan normalization as part of a broader machine learning framework to enable model external generalizability to predict ICI response in non-small cell lung cancer (NSCLC) patients across different centers.MethodsRadiomics features were extracted and compared from 642 advanced NSCLC patients on pre-ICI scans using established open-source PyRadiomics and a proprietary DeepRadiomics deep learning technology. The population was separated into two groups: a discovery cohort of 512 NSCLC patients from three academic centers and a validation cohort that included 130 NSCLC patients from a fourth center. We harmonized images to account for variations in reconstruction kernel, slice thicknesses, and device manufacturers. Multivariable models, evaluated using cross-validation, were used to estimate the predictive value of clinical variables, PD-L1 expression, and PyRadiomics or DeepRadiomics for progression-free survival at 6 months (PFS-6).ResultsThe best prognostic factor for PFS-6, excluding radiomics features, was obtained with the combination of Clinical + PD-L1 expression (AUC = 0.66 in the discovery and 0.62 in the validation cohort). Without image harmonization, combining Clinical + PyRadiomics or DeepRadiomics delivered an AUC = 0.69 and 0.69, respectively, in the discovery cohort, but dropped to 0.57 and 0.52, in the validation cohort. This lack of generalizability was consistent with observations in principal component analysis clustered by CT scan parameters. Subsequently, image harmonization eliminated these clusters. The combination of Clinical + DeepRadiomics reached an AUC = 0.67 and 0.63 in the discovery and validation cohort, respectively. Conversely, the combination of Clinical + PyRadiomics failed generalizability validations, with AUC = 0.66 and 0.59.ConclusionWe demonstrated that a risk prediction model combining Clinical + DeepRadiomics was generalizable following CT scan harmonization and machine learning generalization methods. These results had similar performances to routine oncology practice using Clinical + PD-L1. This study supports the strong potential of radiomics as a future non-invasive strategy to predict ICI response in advanced NSCLC.
Cigarette smoke stimulates clonal expansion of Jak2V617F and Tet2-/- cells
Authors: Ramanathan Gajalakshmi , Chen Jane H. , Mehrotra Nitya , Trieu Tiffany , Huang Aaron , Mas Eduard , Monterrosa Mena Jessica E. , Bliss Bishop , Herman David A. , Kleinman Michael T. , Fleischman Angela G. 
Published: July 2023

IntroductionSomatic mutations in myeloid growth factor pathway genes, such as JAK2, and genes involved in epigenetic regulation, such as TET2, in hematopoietic stem cells (HSCs) leads to clonal hematopoiesis of indeterminate potential (CHIP) which presents a risk factor for hematologic malignancy and cardiovascular disease. Smoking behavior has been repeatedly associated with the occurrence of CHIP but whether smoking is an environmental inflammatory stressor in promoting clonal expansion has not been investigated.MethodsWe performed in vivo smoke exposures in both wildtype (WT) mice and transplanted mice carrying Jak2V617F mutant and Tet2 knockout (Tet-/-) cells to determine the impact of cigarette smoke (CS) in the HSC compartment as well as favoring mutant cell expansion.ResultsWT mice exposed to smoke displayed increased oxidative stress in long-term HSCs and suppression of the hematopoietic stem and progenitor compartment but smoke exposure did not translate to impaired hematopoietic reconstitution in primary bone marrow transplants. Gene expression analysis of hematopoietic cells in the bone marrow identified an imbalance between Th17 and Treg immune cells suggesting a local inflammatory environment. We also observed enhanced survival of Jak2V617F cells exposed to CS in vivo and cigarette smoke extract (CSE) in vitro. WT bone marrow hematopoietic cells from WT/Jak2V617F chimeric mice exposed to CS demonstrated an increase in neutrophil abundance and distinct overexpression of bone marrow stromal antigen 2 (Bst2) and retinoic acid early transcript 1 (Raet1) targets. Bst2 and Raet1 are indicative of increased interferon signaling and cellular stress including oxidative stress and DNA damage, respectively. In chimeric mice containing both WT and Tet2-/- cells, we observed an increased percentage of circulating mutant cells in peripheral blood post-cigarette smoke exposure when compared to pre-exposure levels while this difference was absent in air-exposed controls.ConclusionAltogether, these findings demonstrate that CS results in an inflamed bone marrow environment that provides a selection pressure for existing CHIP mutations such as Jak2V617F and Tet2 loss-of-function.
Revisited role of the placenta in bile acid homeostasis
Authors: Ontsouka Edgar , Schroeder Mariana , Albrecht Christiane 
Published: July 2023

To date, the discussion concerning bile acids (BAs) during gestation is almost exclusively linked to pregnancy complications such as intrahepatic cholestasis of pregnancy (ICP) when maternal serum BA levels reach very high concentrations (&gt;100 μM). Generally, the placenta is believed to serve as a protective barrier avoiding exposure of the growing fetus to excessive amounts of maternal BAs that might cause detrimental effects (e.g., intrauterine growth restriction and/or increased vulnerability to metabolic diseases). However, little is known about the precise role of the placenta in BA biosynthesis, transport, and metabolism in healthy pregnancies when serum BAs are at physiological levels (i.e., low maternal and high fetal BA concentrations). It is well known that primary BAs are synthesized from cholesterol in the liver and are later modified to secondary BA species by colonic bacteria. Besides the liver, BA synthesis in extrahepatic sites such as the brain elicits neuroprotective actions through inhibition of apoptosis as well as oxidative and endoplasmic reticulum stress. Even though historically BAs were thought to be only “detergent molecules” required for intestinal absorption of dietary fats, they are nowadays acknowledged as full signaling molecules. They modulate a myriad of signaling pathways with functional consequences on essential processes such as gluconeogenesis -one of the principal energy sources of the fetus- and cellular proliferation. The current manuscript discusses the potential multipotent roles of physiologically circulating BAs on developmental processes during gestation and provides a novel perspective in terms of the importance of the placenta as a previously unknown source of BAs. Since the principle “not too much, not too little” applicable to other signaling molecules may be also true for BAs, the risks associated with fetal exposure to excessive levels of BAs are discussed.
Sex difference in the association between blood alcohol concentration and serum ferritin
Authors: Yehia Asmaa , Sousa Ricardo A. L. , Abulseoud Osama A. 
Published: July 2023

IntroductionThe sex difference in alcohol use disorder (AUD) is ingrained in distinctive neurobiological responses between men and women, which necessitates further investigation for a more tailored management.MethodsMinding the findings of iron dysregulation in AUD and the sex difference in iron homeostasis in multiple physiological and pathological settings, we examined the sex difference in the association between serum ferritin and blood alcohol concentration (BAC) in intoxicated males (n = 125) and females (n = 59). We included patients with both serum ferritin tested of any value and a BAC above the level of detection during the same hospital admission period. We investigated sex difference in the relationship between BAC, serum ferritin and liver enzymes in intoxicated critically ill and noncritically ill patients.ResultsWe found a negative association between serum ferritin and BAC in critically ill, intoxicated females [R2 = 0.44, F(1,14) = 11.02, p = 0.005], with much attenuated serum ferritin in females compared to their male counterparts (194.5 ± 280.4 vs. 806.3 ± 3405.7 ng/L, p = 0.002). We found a positive association between serum ferritin and liver enzymes [alanine transaminase (ALT) and aspartate transferase (AST)] in critically ill intoxicated females [ALT: R2 = 0.48, F(1,10) = 9.1, p = 0.013; AST: R2 = 0.68, F(1,10) = 21.2, p = 0.001] and in noncritically ill intoxicated males [ALT: R2 = 0.1, F(1,83) = 9.4, p = 0.003; AST: R2 = 0.1, F(1,78) = 10.5, p = 0.002]. The effect of BAC on serum ferritin was not mediated by ALT [indirect effect: (B = 0.13, p = 0.1)]. We also found a significant effect of sex, anemia, intensive care unit (ICU) admission and mortality on serum ferritin.DiscussionOur results suggest that high BAC in intoxicated female patients is associated with attenuated serum ferritin levels, questioning the role of low serum ferritin in female vulnerability to alcohol.
Impact of smart device use on objective and subjective health of older adults: findings from four provinces in China
Authors: Wei Yan , Guo Xinyu 
Published: July 2023

BackgroundThe digital divide has grown because of the deepening digitalization of the Chinese society and the intersection between high-end technology and the age structure. Older adults show an increasing level of weakness in digital life integration. What digital development can bring to older adults is a pressing concern.ObjectiveThis study aims to investigate how smart device use affects older adults' health status and offers an empirical reference for improving their digital literacy and health.MethodsThe data in this study were collected from an offline survey conducted from December 2021 to April 2022, which obtained 1110 valid samples of older adults This study used a multivariate ordered logit model, mediating effect model, and heterogeneity test to analyze the impact of smart device use on the health status of older adults.ResultsSmart device use has a significant positive effect on the self-rated, physical, and psychological health of older adults, and this positive effect is more pronounced among older adults living in urban areas or with a higher age. The average net effect of smart devices on each health status of older adults is 0.161 for self-rated health, 0.155 for physical health, and 0.071 for psychological health. In-depth research found that older adults' attitudes toward smart devices played a mediating role in the influence of smart device use on self-rated and psychological health respectively.ConclusionsThe study found that smart device use had a positive effect on the health status of older adults and that the performance expectations and individualized needs of older adults exhibited an effective linkage between smart devices and health status. Smart device use could improve the overall health of older adults, especially the urban and low-age older adults. Promoting the understanding of the practicality of smart devices for older adults and the aging-oriented transformation of smart devices is an effective way to improve the health status of older adults. The findings provide theoretical support for the wide application of smart devices in older adults, and can effectively help eHealth practitioners implement accurate geriatric health support strategies.
Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis
Authors: Peng Aiyu , Gong Chunmei , Xu Yuanfei , Liang Xiongshun , Chen Xiaoping , Hong Wenxu , Yan Junxia 
Published: July 2023

BackgroundVariants in organic cation transporter (OCT) genes play a crucial role in metformin pharmacokinetics and are critical for diabetes treatment. However, studies investigating the effect of OCT genetic polymorphisms on metformin response have reported inconsistent results. This review and meta-analysis aimed to evaluate the associations between OCT genetic polymorphisms and metformin response and intolerance in individuals with type 2 diabetes mellitus (T2DM).MethodA systematic search was conducted on PubMed, EMBASE, CNKI, WANFANG DATA, and VIP database for identifying potential studies up to 10 November 2022. The Q-Genie tool was used to evaluate the quality of included studies. Pooled odds ratios (OR) or standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated to determine the associations between OCT genetic polymorphisms and metformin response and intolerance that were reflected by glycemic response indexes, such as glycated hemoglobin level (HbA1c%) or change in glycated hemoglobin level (ΔHbA1c%), fasting plasma level (FPG) or change in fasting plasma glucose level (ΔFPG), the effectiveness rate of metformin treatment, and the rate of metformin intolerance. A qualitative review was performed for the variants identified just in one study and those that could not undergo pooling analysis.ResultsA total of 30 related eligible studies about OCT genes (SLC22A1, SLC22A2, and SLC22A3) and metformin pharmacogenetics were identified, and 14, 3, and 6 single nucleotide polymorphisms (SNPs) in SLC22A1, SLC22A2, and SLC22A3, respectively, were investigated. Meta-analysis showed that the SLC22A1 rs622342 polymorphism was associated with a reduction in HbA1c level (AA vs. AC: SMD [95% CI] = −0.45 [−0.73–−0.18]; p = 0.001). The GG genotype of the SLC22A1 rs628031 polymorphism was associated with a reduction in FPG level (GG vs. AA: SMD [95 %CI] = −0.60 [−1.04–0.16], p = 0.007; GG vs. AG: −0.45 [−0.67–0.20], p &lt; 0.001). No statistical association was found between the remaining variants and metformin response and intolerance.ConclusionSLC22A1 rs622342 and rs628031 polymorphisms were potentially associated with glycemic response to metformin. This evidence may provide novel insight into gene-oriented personalized medicine for diabetes.