bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel protein biomarkers for pneumonia and acute exacerbations in COPD: a pilot study
Authors: Jung Anna Lena , Han Maria , Griss Kathrin , Bertrams Wilhelm , Nell Christoph , Greulich Timm , Klemmer Andreas , Pott Hendrik , Heider Dominik , Vogelmeier Claus F. , Hippenstiel Stefan , Suttorp Norbert , Schmeck Bernd 
Published: June 2023

IntroductionCommunity-acquired pneumonia (CAP) and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in high morbidity, mortality, and socio-economic burden. The usage of easily accessible biomarkers informing on disease entity, severity, prognosis, and pathophysiological endotypes is limited in clinical practice. Here, we have analyzed selected plasma markers for their value in differential diagnosis and severity grading in a clinical cohort.MethodsA pilot cohort of hospitalized patients suffering from CAP (n = 27), AECOPD (n = 10), and healthy subjects (n = 22) were characterized clinically. Clinical scores (PSI, CURB, CRB65, GOLD I-IV, and GOLD ABCD) were obtained, and interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2-receptor (IL-2R), lipopolysaccharide-binding protein (LBP), resistin, thrombospondin-1 (TSP-1), lactotransferrin (LTF), neutrophil gelatinase-associated lipocalin (NGAL), neutrophil-elastase-2 (ELA2), hepatocyte growth factor (HGF), soluble Fas (sFas), as well as TNF-related apoptosis-inducing ligand (TRAIL) were measured in plasma.ResultsIn CAP patients and healthy volunteers, we found significantly different levels of ELA2, HGF, IL-2R, IL-6, IL-8, LBP, resistin, LTF, and TRAIL. The panel of LBP, sFas, and TRAIL could discriminate between uncomplicated and severe CAP. AECOPD patients showed significantly different levels of LTF and TRAIL compared to healthy subjects. Ensemble feature selection revealed that CAP and AECOPD can be discriminated by IL-6, resistin, together with IL-2R. These factors even allow the differentiation between COPD patients suffering from an exacerbation or pneumonia.DiscussionTaken together, we identified immune mediators in patient plasma that provide information on differential diagnosis and disease severity and can therefore serve as biomarkers. Further studies are required for validation in bigger cohorts.
Decoding the genetic relationship between Alzheimer’s disease and type 2 diabetes: potential risk variants and future direction for North Africa
Authors: Boukhalfa Wided , Jmel Haifa , Kheriji Nadia , Gouiza Ismail , Dallali Hamza , Hechmi Mariem , Kefi Rym 
Published: June 2023

IntroductionAlzheimer’s disease (AD) and Type 2 diabetes (T2D) are both age-associated diseases. Identification of shared genes could help develop early diagnosis and preventive strategies. Although genetic background plays a crucial role in these diseases, we noticed an underrepresentation tendency of North African populations in omics studies.Materials and methodsFirst, we conducted a comprehensive review of genes and pathways shared between T2D and AD through PubMed. Then, the function of the identified genes and variants was investigated using annotation tools including PolyPhen2, RegulomeDB, and miRdSNP. Pathways enrichment analyses were performed with g:Profiler and EnrichmentMap. Next, we analyzed variant distributions in 16 worldwide populations using PLINK2, R, and STRUCTURE software. Finally, we performed an inter-ethnic comparison based on the minor allele frequency of T2D-AD common variants.ResultsA total of 59 eligible papers were included in our study. We found 231 variants and 363 genes shared between T2D and AD. Variant annotation revealed six single nucleotide polymorphisms (SNP) with a high pathogenic score, three SNPs with regulatory effects on the brain, and six SNPs with potential effects on miRNA-binding sites. The miRNAs affected were implicated in T2D, insulin signaling pathways, and AD. Moreover, replicated genes were significantly enriched in pathways related to plasma protein binding, positive regulation of amyloid fibril deposition, microglia activation, and cholesterol metabolism. Multidimensional screening performed based on the 363 shared genes showed that main North African populations are clustered together and are divergent from other worldwide populations. Interestingly, our results showed that 49 SNP associated with T2D and AD were present in North African populations. Among them, 11 variants located in DNM3, CFH, PPARG, ROHA, AGER, CLU, BDNF1, CST9, and PLCG1 genes display significant differences in risk allele frequencies between North African and other populations.ConclusionOur study highlighted the complexity and the unique molecular architecture of North African populations regarding T2D-AD shared genes. In conclusion, we emphasize the importance of T2D-AD shared genes and ethnicity-specific investigation studies for a better understanding of the link behind these diseases and to develop accurate diagnoses using personalized genetic biomarkers.
Regulation of enteric nervous system via sacral nerve stimulation in opioid-induced constipated rats
Authors: Wang Liyun , Gharibani Payam , Yang Yi , Guo Yu , Yin Jieyun 
Published: June 2023

ObjectivesSacral nerve stimulation (SNS) has been employed for treating constipation. However, its mechanisms involving enteric nervous system (ENS) and motility are largely unknown. In this study, we investigated the possible ENS involvement of SNS in treating Loperamide-induced constipation in rats.MethodsExperiment-1 was designed to study the effects of acute SNS on whole colon transit time (CTT). In experiment-2, we induced constipation by Loperamide and then applied daily SNS or sham-SNS for 1 week. Choline acetyltransferase (ChAT), nitric oxide synthase (nNOS), and PGP9.5 in colon tissue were examined at the end of the study. Moreover, survival factors such as phosphorylated AKT (p-AKT) and Glial cell-derived neurotrophic factor (GDNF) were measures by immunohistochemistry (IHC) and western blot (WB).Key results(1) SNS with one set of parameters shortened CTT starting at 90 min after phenol red administration (p &lt; 0.05). (2) While Loperamide induced slow transit constipation with a significant reduction in fecal pellet number and feces wet weight, daily SNS for a week resolved constipation. (3) Moreover, SNS was able to shorten whole gut transit time comparing to sham-SNS (p = 0.01). (4) Loperamide reduced the number of PGP9.5 and ChAT positive cells, and downregulated ChAT protein expression and upregulated nNOS protein expression, whereas these detrimental effects were significantly reversed by SNS. (5) Furthermore, SNS increased expressions of both GDNF and p-AKT in colon tissue. (6) Vagal activity was reduced following Loperamide (p &lt; 0.01); yet SNS normalized vagal activity.ConclusionSNS with appropriate parameters improves opioid-induced constipation and reversed the detrimental effects of Loperamide on enteric neurons possibly via the GDNF-PI3K/Akt pathway.GRAPHICAL ABSTRACT
Impaired large-scale cortico–hippocampal network connectivity, including the anterior temporal and posterior medial systems, and its associations with cognition in patients with first-episode schizophrenia
Authors: Xue Kangkang , Chen Jingli , Wei Yarui , Chen Yuan , Han Shaoqiang , Wang Caihong , Zhang Yong , Song Xueqin , Cheng Jingliang 
Published: June 2023

Background and objectiveThe cortico–hippocampal network is an emerging neural framework with striking evidence that it supports cognition in humans, especially memory; this network includes the anterior temporal (AT) system, the posterior medial (PM) system, the anterior hippocampus (aHIPPO), and the posterior hippocampus (pHIPPO). This study aimed to detect aberrant patterns of functional connectivity within and between large-scale cortico–hippocampal networks in first-episode schizophrenia patients compared with a healthy control group via resting-state functional magnetic resonance imaging (rs-fMRI) and to explore the correlations of these aberrant patterns with cognition.MethodsA total of 86 first-episode, drug-naïve schizophrenia patients and 102 healthy controls (HC) were recruited to undergo rs-fMRI examinations and clinical evaluations. We conducted large-scale edge-based network analysis to characterize the functional architecture of the cortico–hippocampus network and investigate between-group differences in within/between-network functional connectivity. Additionally, we explored the associations of functional connectivity (FC) abnormalities with clinical characteristics, including scores on the Positive and Negative Syndrome Scale (PANSS) and cognitive scores.ResultsCompared with the HC group, schizophrenia patients exhibited widespread alterations to within-network FC of the cortico–hippocampal network, with decreases in FC involving the precuneus (PREC), amygdala (AMYG), parahippocampal cortex (PHC), orbitofrontal cortex (OFC), perirhinal cortex (PRC), retrosplenial cortex (RSC), posterior cingulate cortex (PCC), angular gyrus (ANG), aHIPPO, and pHIPPO. Schizophrenia patients also showed abnormalities in large-scale between-network FC of the cortico–hippocampal network, in the form of significantly decreased FC between the AT and the PM, the AT and the aHIPPO, the PM and the aHIPPO, and the aHIPPO and the pHIPPO. A number of these signatures of aberrant FC were correlated with PANSS score (positive, negative, and total score) and with scores on cognitive test battery items, including attention/vigilance (AV), working memory (WM), verbal learning and memory (Verb_Lrng), visual learning and memory (Vis_Lrng), reasoning and problem-solving (RPS), and social cognition (SC).ConclusionSchizophrenia patients show distinct patterns of functional integration and separation both within and between large-scale cortico–hippocampal networks, reflecting a network imbalance of the hippocampal long axis with the AT and PM systems, which regulate cognitive domains (mainly Vis_Lrng, Verb_Lrng, WM, and RPS), and particularly involving alterations to FC of the AT system and the aHIPPO. These findings provide new insights into the neurofunctional markers of schizophrenia.
Survival status and predictors of mortality from severe community-acquired pneumonia among under-five children admitted at Debre Tabor comprehensive specialized hospital: a prospective cohort study
Authors: Kassaw Amare , Kerebih Gashaw , Zeleke Shegaw , Chanie Ermias Sisay , Dessalegn Nigatu , Bante Berihun , Teshome Asefa Ageghehu , Chekole Bogale , Gelaw Belete , Bayih Wubet Alebachew , Tesfaw Aragaw , Feleke Dejen Getaneh , Kefale Demewoz , Azmeraw Molla , Chanie Aynadis , Awoke Getaneh , Moges Natnael 
Published: June 2023

BackgroundGlobally, Pneumonia continues to be the leading cause of mortality among under-five children. Ethiopia ranks fourth out of 15 countries worldwide in terms of the highest death rate of under-five children due to severe community-acquired pneumonia (SCAP). However, to date, there is no recent study that shows survival status and predictors of mortality from SCAP. Therefore, this study aimed to determine survival status and predictors of mortality from this dangerous disease among under-five children.MethodsA facility-based prospective cohort study was conducted from 1 November 2021 to 31 October 2022 at Debre Tabor comprehensive specialized hospital. All under-five children with SCAP admitted during the study period were included. Participants were selected using a systematic sampling technique. The collected data were coded, edited, and entered into epi-data version 4.2 and then exported to STATA version 17 for further analysis. The Kaplan Meier failure estimate with log-rank test was employed to determine the survival estimates. A cox-proportional hazard regression model was fitted to identify significant variables.ResultsThe overall incidence density rate of mortality was 5.7 /1000 children with a median hospital stay of 8.2 days. Heart disease (AHR: 4.37; 95%CI: 1.68–11.32), previous admission of SCAP (AHR: 3.87; 95% CI: 1.31–11.43), WFL &lt; −3Z score (AHR: 3.57; 95% CI: 1.02–12.42), impaired consciousness level at admission 3.41(1.14–10.19), and pleural effusion (AHR: 3.42; 95%CI: 1.18–9.93) were significant predictors of mortality.ConclusionIn this study, the survival probability of children with SCAP was low. Children with heart disease, previous admission of SCAP, WFL &lt; −3Z score, impaired consciousness level at admission, and pleural effusion had low survival. Therefore, much emphasis is needed on children with SCAP, particularly those with identified predictors.
A retrospective analysis of factors associated with the length of hospital stay in COVID-19 patients treated with Nirmatrelvir / Ritonavir
Authors: Zheng Jiantao , Hong Wencong , Zhou Chanjuan , Hong Donghuang , Yan Hong , Shen Yanghui 
Published: June 2023

Objectives: This study reviewed factors influencing the length of hospital stay in adult inpatients with confirmed Coronavirus disease (COVID-19) who were treated with Nirmatrelvir/Ritonavir.Methods: We did a retrospective analysis of data from a cohort of inpatients with confirmed diagnosis of Omicron variant of SARS-CoV-2 infection who were treated with Nirmatrelvir/Ritonavir. We included patients who were treated from 13th March 2022 to 6th May 2022 in various in-patient treatment units in Quanzhou, Fujian Province, China. The primary study outcome was the length of hospital stay. Secondary study outcome was viral elimination defined as negative for ORF1ab and N genes [cycle threshold (Ct) value ≥35 in real-time PCR], according to local guidelines. Hazard ratios (HR) of event outcomes were analyzed using Multivariate Cox regression models.Results: We studied 31 inpatients with high risk for severe COVID-19 who were treated with Nirmatrelvir/Ritonavir. We found that inpatients with shorter length of hospital stay (≤17 days) were mostly females with lower body mass index (BMI) and Charlson Comorbidity Index (CCI) index. Their treatment regimen with Nirmatrelvir/Ritonavir was started within 5 days of diagnosis (p &lt; 0.05). Multivariate Cox regression indicated that inpatients starting treatment of Nirmatrelvir/Ritonavir within 5 days had a shorter length of hospital stay (HR 3.573, p = 0.004) and had a faster clearance of viral load (HR 2.755, p = 0.043).Conclusion: This study assumes relevance during the Omicron BA.2 epidemic as our findings suggest that early treatment with Nirmatrelvir/Ritonavir within 5 days of diagnosis (≤5 days) was highly effective in shortening the length of hospital stay and faster viral load clearance.
Cost-effectiveness of adding empagliflozin to the standard of care for patients with heart failure with reduced ejection fraction from the perspective of healthcare system in Malaysia
Authors: Ong Siew Chin , Low Joo Zheng , Linden Stephan 
Published: June 2023

Objective: The aim of this study was to determine the cost-effectiveness of adding empagliflozin to the standard of care versus SoC alone for the treatment of patients with heart failure (HF) with reduced ejection fraction (HFrEF) from the perspective of the Ministry of Health of Malaysia.Methods: A cohort-based transition-state model, with health states defined as Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) quartiles and death, was used to determine the lifetime direct medical costs and quality-adjusted life years (QALYs) for both treatment groups. The risks of all-cause death, cardiovascular death, and health state utilities were estimated from the EMPEROR-Reduced trial. The incremental cost-effectiveness ratio (ICER) was assessed against the cost-effectiveness threshold (CET) as defined by the country’s gross domestic product per capita (RM 47,439 per QALY) to determine cost-effectiveness. Sensitivity analyses were conducted to assess the key model parameters’ uncertainty in respect to the incremental cost-effectiveness ratio. A scenario analysis was performed using health states as defined by the New York Heart Association classes.Results: Compared to SoC alone, empagliflozin + SoC for the treatment of HFrEF was more expensive (RM 25,333 vs. RM 21,675) but gained more health utilities (3.64 vs. 3.46), resulting in an ICER of RM 20,400 per QALY in the KCCQ-CSS model. A NYHA-based scenario analysis generated an ICER of RM 36,682 per QALY. A deterministic sensitivity analysis confirmed the robustness of the model in identifying the empagliflozin cost as the main driver of cost-effectiveness. The ICER was reduced to RM 6,621 when the government medication purchasing prices were used. A probabilistic sensitivity analysis with a CET of 1xGDP per capita reached 72.9% probability for empagliflozin + SoC against SoC being cost-effective.Conclusion: Empagliflozin + SoC compared to SoC alone for the treatment of HFrEF patients was cost-effective from the perspective of the MoH of Malaysia.
Relationship between family background and self-efficacy in adolescent table tennis players: a moderated mediation model
Authors: He Ke , Li Weiming , Li Zihao 
Published: June 2023

IntroductionA moderated mediation model was constructed in this study to clarify the relationship between family background and self-efficacy of adolescent table tennis players, focusing on the mediating effect of technical learning engagement in the relationship as well as the moderating role of factors such as gender and training years.Methods189 adolescent table tennis players (age: 13.69±1.28 years) were investigated as subjects using a questionnaire method.Results(1) Family background, technical learning engagement, and self-efficacy were significantly and positively correlated (p&lt;0.01), with girls’ technical learning engagement (Mfemale=5.81, Mmale=5.19, p&lt;0.01) and self-efficacy (Mfemale=3.34, Mmale=2.66, p&lt;0.01) significantly higher than boys’; (2) Technical learning engagement partially mediated the effect of family background on self-efficacy (ab=0.10, boot SE=0.02,95% CI=[0.07, 0.14]); (3) The first half of technical learning engagement’s mediating role was moderated by gender (B=0.05, p&lt;0.01), with a more significant influence of family background on boys’ (B=0.24, p&lt;0.001, 95% CI=[0.22, 0.26]) technical learning engagement than girls’ (B=0.19, p&lt;0.001, 95% CI=[0.17, 0.21]); (4) The second half of technical learning engagement’s mediating role was moderated by training years (B=–0.21, p&lt;0.001), with a more significant influence of technical learning engagement on the self-efficacy of adolescents with fewer training years (B=0.54, p&lt;0.001, 95% CI=[0.39, 0.68]). The positive effect of technical learning engagement on self-efficacy gradually diminished with increasing training years, and the moderating effect of training years disappeared when the training years reached 8.94 years.Conclusion(1) More attention should be paid to adolescent table tennis players with poor family backgrounds, who are more likely to have low self-efficacy. (2) Parents should never neglect their initiative in providing guidance and support to adolescent players involved in long-term professional table tennis training, especially for boys. (3) Coaches should pay close attention to the level of technical learning engagement of players with long training years, who are more likely to have lower self-efficacy as a result of their own emotional experiences, stagnant performance, etc.
Speakers are more cooperative and less individual when interacting in larger group sizes
Authors: Pellegrino Elisa , Dellwo Volker 
Published: June 2023

IntroductionCooperation, acoustically signaled through vocal convergence, is facilitated when group members are more similar. Excessive vocal convergence may, however, weaken individual recognizability. This study aimed to explore whether constraints to convergence can arise in circumstances where interlocutors need to enhance their vocal individuality. Therefore, we tested the effects of group size (3 and 5 interactants) on vocal convergence and individualization in a social communication scenario in which individual recognition by voice is at stake.MethodsIn an interactive game, players had to recognize each other through their voices while solving a cooperative task online. The vocal similarity was quantified through similarities in speaker i-vectors obtained through probabilistic linear discriminant analysis (PLDA). Speaker recognition performance was measured through the system Equal Error Rate (EER).ResultsVocal similarity between-speakers increased with a larger group size which indicates a higher cooperative vocal behavior. At the same time, there was an increase in EER for the same speakers between the smaller and the larger group size, meaning a decrease in overall recognition performance.DiscussionThe decrease in vocal individualization in the larger group size suggests that ingroup cooperation and social cohesion conveyed through acoustic convergence have priority over individualization in larger groups of unacquainted speakers.
Stop it! Relationship between sport expertise and response inhibition in elite athletes
Authors: Fleddermann Marie-Therese , Reichert Lukas , Wieland Björn , Zentgraf Karen 
Published: June 2023

IntroductionThe dynamic structure of sport games forces players to make time-sensitive decisions and to initiate actions that may then have to be canceled in response to sudden changes in the game situation. Whether and up to which time already initiated movements can still be inhibited is an important criterion for game performance in elite sport. Research indicates that elite athletes show superior motor inhibition performance compared to recreational athletes. However, no study has examined whether differences also emerge among professional elite athletes themselves. Therefore, this study aimed to investigate whether motor inhibition performance is a differential feature among elite athletes, and whether inhibition performance increases with greater expertise.MethodsIn total of 106 elite athletes (ice hockey, basketball, volleyball, American football, handball, and soccer) completed a PC-based procedure to determine motor inhibition performance using the stop-signal reaction time (SSRT) task for hands and feet. In addition, an expertise score was determined for each elite athlete. Multiple linear regression was used to calculate the relationship between expertise and SSRT.ResultsResults showed that the expertise score of the elite athletes was between 3.7 and 11.7 out of 16 possible points (MExpertise = 6.8 points, SD = 1.76). The average SSRT of the hands was 224.0 ms (SD = 35.0); of the feet, 257.9 ms (SD = 48.5). Regression results showed a significant relationship between expertise and SSRT (F(2,101) = 9.38, p = 0.04, R2 = 0.06). SSRTs of the hands were significant predictors of expertise (b = −0.23, t = −2.1, p = 0.04).DiscussionTaken together, results suggest that elite athletes with higher expertise outperform elite athletes with lower expertise, indicating that it is possible to differentiate within elite athletes with respect to inhibition performance of the hands. However, whether expertise affects inhibition performance or vice versa cannot be answered at present.