bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do proton pump inhibitors alter the response to immune checkpoint inhibitors in cancer patients? A meta-analysis
Authors: Lopes Sébastien , Pabst Lucile , Dory Anne , Klotz Marion , Gourieux Bénédicte , Michel Bruno , Mascaux Céline 
Published: January 2023

IntroductionGut microbiota can significantly affect the effectiveness of immune checkpoint inhibitors (ICIs) in cancer patients. Recently, antibiotics were shown to decrease survival rate of patients treated by ICIs. Proton pump inhibitors (PPIs) can indeed modulate microbiota’s diversity, therefore altering ICIs response. A meta-analysis was performed based on published data to verify this hypothesis.MethodsIn this study, over 41 publications, exploring the impact of concomitant PPI treatment on outcomes of ICI-treated patients, were analyzed. Evaluated endpoints were overall survival (OS) and progression-free survival (PFS). Pooled hazard ratios (HRs) with a 95% confidence interval (CI) were reported in ICIs in PPI users versus non-PPI users. Subgroup analyses were performed to minimize the impact of study heterogeneity and to investigate the influence of PPI on the different groups of interest. There was no evidence of publication bias for OS and PFS analysis in subgroup analysis.ResultsForty-one studies were included in the meta-analysis, including a total of 20,042 patients. OS of patients receiving ICIs was negatively correlated in patients concomitantly treated with PPI (HR=1.37; 95%CI, 1.23–1.52). PFS of cancer patients receiving ICIs was also negatively correlated with PPI treatment (HR=1.28; 95%CI, 1.15–1.42). PPI and ICI use was associated with worst OS and PFS not only for non-small-cell lung cancer (NSCLC) or urothelial cancer patients but also for patients treated with anti PD-1 (OS) and anti PD-L1 (OS and PFS) immunotherapies when administered in non-first line and when PPI was received as baseline treatment or in 60 days before ICI initiation. PPI and ICI use also showed the worst OS and PFS for patients from Europe and Asia.ConclusionThis meta-analysis suggests that PPI treatment leads to significantly worse outcomes in advanced cancer patients treated by ICIs in terms of PFS and OS.
Machine learning models for predicting steroid-resistant of nephrotic syndrome
Authors: Ye Qing , Li Yuzhou , Liu Huihui , Mao Jianhua , Jiang Hangjin 
Published: January 2023

BackgroundIn the absence of effective measures to predict steroid responsiveness, patients with nonhereditary steroid-resistant nephrotic syndrome (SRNS) have a significantly increased risk of progression to end-stage renal disease. In view of the poor outcomes of SRNS, it is urgent to identify the steroid responsiveness of idiopathic nephrotic syndrome (INS) early.MethodsTo build a prediction model for SRNS, we collected 91 subjects; 57 of them had steroid-sensitive nephrotic syndrome, and the others had SRNS. For each subject, 87 clinical variables were measured. In general, only a small part of these variables is informative to SRNS. Thus, we proposed a new variable selection framework including a penalized regression approach (named MLR+TLP) to select variables having a linear effect on the SRNS and a nonparametric screening method (MAC) to select variables having a nonlinear marginal (joint) effect on the SRNS. Thereafter, considering the correlation between selected clinical variables, we used a stepwise method to build our final model for predicting SRNS. In addition, a statistical testing procedure is proposed to test the overfitting of the proposed model.ResultsTwenty-six clinical variables were selected to be informative to SRNS, and an SVM model was built to predict SRNS with a leave-one-out cross-validation (LOO-CV) accuracy of 95.2% (overfitting p value&lt;0.005). To make the model more useful, we incorporate prior medical information into the model and consider the correlation between selected variables. Then, a reduced SVM model including only eight clinical variables (erythrocyte sedimentation rate, urine occult blood, percentage of neutrophils, immunoglobulin A, cholesterol, vinculin autoantibody, aspartate aminotransferase, and prolonged prothrombin time) was built to have a LOO-CV accuracy of 92.8% (overfitting p value&lt;0.005). The validation cohort showed that the reduced model obtained an accuracy of 94.0% (overfitting p value&lt;0.005), with a sensitivity of 90.0% and a specificity of 96.7%. Notably, vinculin autoantibody is the only podocyte autoantibody included in this model. It is linearly related to steroid responsiveness. Finally, our model is freely available as a user-friendly web tool at https://datalinkx.shinyapps.io/srns/.ConclusionThe SRNS prediction model constructed in this study comprehensively and objectively evaluates the internal conditions and disease status of INS patients and will provide scientific guidance for selecting treatment methods for children with nonhereditary SRNS.
Smoking and coronary artery disease risk in patients with diabetes: A Mendelian randomization study
Authors: Chen Songzan , Yang Fangkun , Xu Tian , Wang Yao , Zhang Kaijie , Fu Guosheng , Zhang Wenbin 
Published: January 2023

BackgroundPrevious observational studies have shown an association between smoking and coronary artery disease (CAD) in patients with diabetes. Whether this association reflects causality remains unestablished. This study aimed to explore the causal effect of smoking on CAD in patients with diabetes.MethodsGenetic signatures for smoking were extracted from a large genome-wide association study (GWAS), consisted of up to 1.2 million participants. Four smoking phenotypes were included: smoking initiation, cigarettes per day, age at initiation of regular smoking, and smoking cessation. Genetic associations with CAD in patients with diabetes were extracted from another GWAS, which included 15,666 participants (3,968 CAD cases and 11,696 controls). The analyses were performed using the univariable and multivariable Mendelian randomization (MR) method.ResultsMR analysis revealed that smoking initiation was positively related to CAD risk in patients with diabetes (OR = 1.322, 95% CI = 1.114 – 1.568, P = 0.001), but this association was attenuated when adjusted for cardiovascular risk factors (OR = 1.212, 95% CI = 1.008 – 1.457, P = 0.041). Age at initiation of regular smoking was negatively related to CAD in patients with diabetes (OR = 0.214, 95% CI = 0.070 – 0.656, P = 0.007), but this association became insignificant when adjusted for cardiovascular risk factors.ConclusionsThis study supported the effect of smoking initiation on the risk of CAD in patients with diabetes.
Long-term over-the-horizon microwave channel measurements and statistical analysis in evaporation ducts over the Yellow Sea
Authors: Wang Shuwen , Yang Kunde , Shi Yang , Zhang Hao , Yang Fan , Hu Dawei , Dong Guoyu , Shu Yihang 
Published: January 2023

Maritime high-speed over-the-horizon wireless communication is realizable through evaporation ducts. Detailed measurement, analysis, and modeling of duct channels are essential for application of this communication technique. In this paper, X-band electromagnetic (EM) wave propagation systems were developed and deployed for a 133-km over-the-horizon microwave link in coastal areas of the Yellow Sea. The propagation length was 7.7 times the line-of-sight length. Measurement results including the path loss (PL) and meteorological data were obtained during a 54-day period in autumn 2021. The long-term channel results were analyzed on the basis of statistical analysis and model simulations. Results showed that our measurement system, with a maximum measurable power loss of 200 dB, had connected with a probability of 56.2% during the measurement period. Model simulation showed that evaporation duct environments are not ideal in autumn, with an average evaporation duct height (EDH) of 10.6 m. The land breeze in autumn introduced dry and cold air to the link, which could promote evaporation of seawater and reduce PL by approximately 40 dB. Annual spatiotemporal characteristics of EDH showed that evaporation ducts are most suitable for over-the-horizon communication in spring, especially May.
Bark-inhabiting fungal communities of European chestnut undergo substantial alteration by canker formation following chestnut blight infection
Authors: Douanla-Meli Clovis , Moll Julia 
Published: January 2023

BackgroundChestnut forests are severely threatened by chestnut blight caused by the fungal pathogen Cryphonectria parasitica and the infected trees exhibit bark canker in the later stage of the disease. European chestnut (Castanea sativa) is further infected by Gnomoniopsis smithogilvyi, another canker-causing fungal pathogen. We explored whether and how chestnut blight is reflected in bark-inhabiting fungal communities of European chestnut and also assessed the co-occurrence of C. parasitica and G. smithogilvyi.Materials and methodsWe initially investigated the fungal communities of European chestnut bark tissues and further monitored changes in these fungal communities with regard to disease progression from infection to canker formation by analyzing bark samples from asymptomatic trees, asymptomatic trees with latent C. parasitica infection, and infected trees with canker tissues, using amplicon sequencing of the ITS2 region of rDNA.ResultsThe results showed that fungal community composition and diversity differed between the sample types. The fungal community composition was substantially reshaped by canker formation, whereas latent C. parasitica infection and more specifically pre-canker infection period per se had a weak effect. Fungal communities of canker samples was less diverse and more dissimilar to those of other sample types. C. parasitica dominated the mycobiome of canker samples, whereas G. smithogilvyi was found in only 9% of canker samples at very low abundances. However, G. smithogilvyi was a dominant fungus in the bark of healthy plants.ConclusionThis study highlights that canker formation is the principal driver of decreasing diversity and altered composition of the mycobiome in bark tissues of European chestnut infected by C. parasitica infection. It additionally emphasizes the scarce co-occurrence of C. parasitica and G. smithogilvyi on European chestnut.
Clomazone impact on fungal network complexity and stability
Authors: He Hairong , Huang Jiarui , Zhao Zhenzhu , Feng Weisheng , Zheng Xiaoke , Du Pengqiang 
Published: January 2023

IntroductionSoil fungal network composition and stability are important for soil functions, but there is less understanding of the impact of clomazone on network complexity and stability.MethodsIn this work, two agricultural soils were used to investigate the impact of clomazone on fungal network complexity, composition, and stability. The two soils were treated with clomazone solution (0, 0.8, 8, and 80  mg kg−1) and kept in an incubator.Results and DiscussionUnder the influence of clomazone, the fungal network nodes were decreased by 12–42; however, the average degree was increased by 0.169–1.468 and fungal network density was increased by 0.003–0.054. The keystone nodes were significantly changed after clomazone treatment. Network composition was also impacted. Specifically, compared with control and clomazone treatments in both soils, the shared edges were fewer than 54 in all comparisons, and network dissimilarity was 0.97–0.98. These results suggested that fungal network composition was significantly impacted. The network robustness was increased by 0.0018–0.0209, and vulnerability was decreased by 0.00018–0.00059 in both soils, which indicated that fungal network stability was increased by clomazone. In addition, the functions of network communities were also changed in both soils. These results indicated that clomazone could significantly impact soil fungal networks.
The Evolution of Intein-Based Affinity Methods as Reflected in 30 years of Patent History
Authors: Prabhala Sai Vivek , Gierach Izabela , Wood David W. 
Published: January 2023

Self-cleaving affinity tags, based on engineered intein protein domains, have been touted as a universal single step purification platform for tagless non-mAb proteins. These approaches provide all of the power and flexibility of tag-based affinity methods, but deliver a tagless target protein suitable for clinical applications without complex process development. This combination of features might accelerate and de-risk biopharmaceutical development by bridging early discovery to full-scale manufacturing under a single platform. Despite this profound promise, intein-based technologies have yet to reach their full potential. This review examines the evolution of intein-based purification methods in the light of several significant intein patents filed over the last 3 decades. Illustrated with actual key figures from each of the relevant patents, key advances are described with a focus on applications in basic research and biopharmaceutical production. Suggestions for extending intein-based purification systems to emerging therapies and non-protein applications are presented as concluding remarks.
Optimizing the mnemonic similarity task for efficient, widespread use
Authors: Stark Craig E. L. , Noche Jessica A. , Ebersberger Jarrett R. , Mayer Lizabeth , Stark Shauna M. 
Published: January 2023

Introduction: The Mnemonic Similarity Task (MST) has become a popular test of memory and, in particular, of hippocampal function. It has been heavily used in research settings and is currently included as an alternate outcome measure on a number of clinical trials. However, as it typically requires ~15 min to administer and benefits substantially from an experienced test administrator to ensure the instructions are well-understood, its use in trials and in other settings is somewhat restricted. Several different variants of the MST are in common use that alter the task format (study-test vs. continuous) and the response prompt given to participants (old/similar/new vs. old/new).Methods: In eight online experiments, we sought to address three main goals: (1) To determine whether a robust version of the task could be created that could be conducted in half the traditional time; (2) To determine whether the test format or response prompt choice significantly impacted the MST’s results; and (3) To determine how robust the MST is to repeat testing. In Experiments 1–7, participants received both the traditional and alternate forms of the MST to determine how well the alternate version captured the traditional task’s performance. In Experiment 8, participants were given the MST four times over approximately 4 weeks.Results: In Experiments 1–7, we found that test format had no effect on the reliability of the MST, but that shifting to the two-choice response format significantly reduced its ability to reflect the traditional MST’s score. We also found that the full running time could be cut it half or less without appreciable reduction in reliability. We confirmed the efficacy of this reduced task in older adults as well. Here, and in Experiment 8, we found that while there often are no effects of repeat-testing, small effects are possible, but appear limited to the initial testing session.Discussion: The optimized version of the task developed here (oMST) is freely available for web-based experiment delivery and provides an accurate estimate of the same memory ability as the classic MST in less than half the time.
Preadolescent exposure to a sexually mature, unrelated male rat reduces postadolescent social recognition memory and CA2 c-Fos labeling
Authors: Maletta Teresa , Palummieri Michael , Correa Jeff , Holahan Matthew R. 
Published: January 2023

IntroductionSocial memory involves social recognition: the ability to discriminate between two or more conspecifics when one has been previously encountered. The CA2 region of the hippocampus has been implicated in social memory, as lesions and dysfunction to this area lead to social memory impairments. A variety of psychogenic manipulations during postnatal sensitive developmental periods are associated with social memory impairments later in life.MethodsIn this study, we exposed preadolescent rats to a sexually, mature unrelated male and examined whether this was associated with changes in postadolescent social memory and c-Fos labeling in the CA2 region. Male and female Long-Evans rats were exposed to a male, adult rat on postnatal days 19–21 (P19–21). Social memory was measured during the postadolescent period and defined as increased interactions towards a novel age-matched rat in contrast to a previously-encountered age-matched rat. After the test, rats were euthanized and brain tissue was then collected to quantify c-Fos labeling within the CA2 region.ResultsCompared to home cage controls and controls not exposed to the adult male, male and female rats exposed to the unrelated adult during preadolescence were unable to discriminate between a novel and previously encountered conspecific during the postadolescent test showing social memory deficits. The groups that showed social recognition deficits also had significantly fewer c-Fos-positive cells within the CA2 region compared to the control groups.DiscussionThese findings indicate that threatening psychogenic encounters during preadolescence can have detrimental long-term effects on social memory potentially via disrupted activity in the CA2 hippocampal region.
Sex differences and risk factors in recurrent ischemic stroke
Authors: Chung Ji Yeon , Lee Bit Na , Kim Young Seo , Shin Byoung-Soo , Kang Hyun Goo 
Published: January 2023

IntroductionRecurrent ischemic stroke (RIS) is associated with increased mortality and poor outcomes. Therefore, secondary prevention is critical for reducing the risk of recurrent stroke. Previous studies have found sex differences in risk factors in patients with first-ever stroke; however, the results have been inconsistent for recurrent stroke. Therefore, this study aimed to investigate whether there are significant sex differences in the clinical characteristics and risk factors for recurrent ischemic stroke.MethodsWe retrospectively studied 787 patients with recurrent ischemic stroke after first-ever stroke confirmation using magnetic resonance imaging (MRI) after visiting a regional tertiary hospital between 2014 and 2020. Demographic characteristics, laboratory findings, and risk factors were compared between the male and female patients. In addition, multivariate logistic regression was performed to identify the independent factors associated with stroke recurrence in male patients.ResultsAmong the 787 patients, 466 (59.2%) were males. Males were younger than females (67.6 vs. 71.9 years). Females had higher rates of hypertension, diabetes mellitus, dyslipidemia, and overweight than those of males. However, the alcohol drinking and smoking rate were significantly higher in males than that in females. There were no statistically significant sex-based differences in the laboratory findings. Among males, hypertension, alcohol drinking, smoking and dyslipidemia was a significant risk factor for ischemic stroke recurrence.ConclusionHypertension and dyslipidemia were significant risk factors of recurrent ischemic stroke in both genders. Smoking and alcohol drinking were significant risk factors associated with ischemic stroke recurrence in males. Therefore, smoking cessation and alcohol abstinence are recommended after the first stroke to prevent recurrent ischemic stroke especially for males. Diabetes was a significant risk factor of ischemic stroke recurrence in females. More extensive studies are needed to understand the causal relationship of each factors with ischemic stroke recurrence according to sex differences and specification of preventive management is needed.
The differences of orthostatic hypotension in patients with Parkinson's disease and multiple system atrophy
Authors: Zeng Jingrong , Xing Yingqi , Mei Shanshan , Xu Baolei , Xue Xiaofan , Song Haixia , Xu Erhe 
Published: January 2023

BackgroundMultiple system atrophy (MSA) and Parkinson's disease (PD) have similar clinical presentations in their early stages. Orthostatic hypotension (OH) is a common autonomic dysfunction associated with MSA and PD. Heart rate (HR) and systolic blood pressure (SBP) changes are measured in response to the active standing test, which is widely used to screen for cardiovascular autonomic function.Objectives and methodsOverall, 255 patients (67 MSA, 188 PD) underwent continuous beat-to-beat non-invasive BP monitoring and active standing test. The total standing time was 10 min, and the BP differences between both groups were compared to determine whether the ΔHR/ΔSBP can differentiate both conditions.ResultsClassical orthostatic hypotension (COH) (52%) and initial OH (19%) were most common in MSA and PD, respectively. MSA had a higher HR (75.0 ± 9.7 vs. 71.0 ± 10.7, P = 0.008) than PD in the supine position. SBP (135.70 ± 15.68 mmHg vs. 127.31 ± 15.14 mmHg, P = 0.106), diastolic BP (78.45 ± 12.36 mmHg vs. 67.15 ± 13.39 mmHg, P = 0.009) and HR (73.94 ± 8.39 bpm vs. 71.08 ± 13.52 bpm, P = 0.389) at baseline were higher in MSA-COH than in PD-COH. After adjusting for age and disease duration, the ΔHR/ΔSBP-10 min significantly discriminated MSA-COH from PD-COH (P = 0.031). An ΔHR/ΔSBP-10 min of 0.517 showed a sensitivity of 67% and specificity of 84% (AUC = 0.77, 95% CI: 0.63–0.91).ConclusionThe SBP, diastolic BP, and HR were higher in the supine position; however, ΔHR and ΔSBP were lower after standing in MSA patients than in PD patients. The ΔHR/ΔSBP-10 min discriminated between MSA-COH and PD-COH with quiet acceptable accuracy.
Confrontation of endolymphatic hydrops diagnosis on 3-Tesla MRI to clinical and audiovestibular findings in Meniere's disease
Authors: Diorflar Sarah , Guigou Caroline , Daguet Edouard , Bensimon Jean-Loup , Toupet Michel , Bozorg-Grayeli Alexis 
Published: January 2023

ObjectiveThe aim of this study was to compare different MRI diagnostic criteria for endolymphatic hydrops (EH) and to investigate the relation between audiovestibular and MRI findings in Meniere's disease (MD).Materials and methodsProspective cross-sectional cohort study in 2 referral centers included 76 patients with unilateral (n = 62) or bilateral (n = 14) MD. All patients underwent inner ear 3T-MRI 4 h (n = 52) or &gt;24H (n = 24) following audiovestibular tests. T2-CISS and 3D-FLAIR images 4H after gadolinium were obtained. EH diagnosis was based on saccular morphology on coronal views (T2 and 3D-FLAIR), semi quantitative estimation of endolymphatic space enlargement, and saccule utricle ratio inversion (SURI) on 3D-FLAIR axial views.ResultsSURI was the best criterion related to the disease side (43 SURI+ on symptomatic ears, n = 77, vs. 6 SURI+ on asymptomatic ears, n = 53, p &lt; 0.0001, Chi-2). Same-day MRI revealed relation between EH, hearing loss and caloric weakness which could not be detected on delayed MRI: SURI was associated with a higher pure-tone average (43 ± 4.1 dB in SURI+ ears, n = 42 vs. 23 ± 2.6 SURI-, n = 62, p &lt; 0.0001, unpaired t-test,), and a higher proportion of vestibular caloric weakness (23/46 SURI+ ears vs. 4/62 SURI-, p &lt; 0.001, Chi-2). Among all criteria, SURI combined to caloric weakness was the best predictor of the affected side in a logistic regression model.ConclusionSURI had the strongest relation to the side the disease and audio vestibular findings for unilateral, probable and definite meniere disease. A short delay between MRI and audio vestibular tests improved the coherence between the findings.