bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progression subtypes in Parkinson’s disease identified by a data-driven multi cohort analysis
Authors: Hähnel Tom , Raschka Tamara , Sapienza Stefano , Klucken Jochen , Glaab Enrico , Corvol Jean-Christophe , Falkenburger Björn H. , Fröhlich Holger 
Published: May 2024

AbstractThe progression of Parkinson’s disease (PD) is heterogeneous across patients, affecting counseling and inflating the number of patients needed to test potential neuroprotective treatments. Moreover, disease subtypes might require different therapies. This work uses a data-driven approach to investigate how observed heterogeneity in PD can be explained by the existence of distinct PD progression subtypes. To derive stable PD progression subtypes in an unbiased manner, we analyzed multimodal longitudinal data from three large PD cohorts and performed extensive cross-cohort validation. A latent time joint mixed-effects model (LTJMM) was used to align patients on a common disease timescale. Progression subtypes were identified by variational deep embedding with recurrence (VaDER). In each cohort, we identified a fast-progressing and a slow-progressing subtype, reflected by different patterns of motor and non-motor symptoms progression, survival rates, treatment response, features extracted from DaTSCAN imaging and digital gait assessments, education, and Alzheimer’s disease pathology. Progression subtypes could be predicted with ROC-AUC up to 0.79 for individual patients when a one-year observation period was used for model training. Simulations demonstrated that enriching clinical trials with fast-progressing patients based on these predictions can reduce the required cohort size by 43%. Our results show that heterogeneity in PD can be explained by two distinct subtypes of PD progression that are stable across cohorts. These subtypes align with the brain-first vs. body-first concept, which potentially provides a biological explanation for subtype differences. Our predictive models will enable clinical trials with significantly lower sample sizes by enriching fast-progressing patients.
Numbers of articles in the three Japanese national newspapers, 1872–2021
Authors: Ogihara Yuji 
Published: May 2024

AbstractNewspapers have been analyzed in many disciplines, including the humanities, social sciences, and natural sciences. However, previous research using Japanese newspapers investigated the absolute frequency (number) of articles of interest and did not examine the relative frequency (rate) of articles, restricting a deeper understanding of humans, society, and nature. The absolute frequency and the relative frequency of articles can show different patterns of results, which leads to different conclusions. Thus, investigating only the absolute frequency of articles is insufficient, or sometimes misleading. Therefore, it is necessary to examine not only the absolute frequency of articles but also their relative frequency. For this purpose, I conducted a series of systematic searches and provided the yearly numbers of articles in the three databases of Japanese national newspapers over the 150 years between 1872 and 2021. This paper enables researchers to calculate the relative frequency of articles, contributing to research in many disciplines.
Chromosome-level genome assembly of the bethylid ectoparasitoid wasp Sclerodermus sp. ‘alternatusi’
Authors: Wan Yi , Wu Hui-Jie , Yang Jia-Peng , Zhang Jin-Li , Shen Zhi-Cheng , Xu Hai-Jun , Ye Yu-Xuan 
Published: May 2024

AbstractThe Bethylidae are the most diverse of Hymenoptera chrysidoid families. As external parasitoids, the bethylids have been widely adopted as biocontrol agents to control insect pests worldwide. Thus far, the genomic information of the family Bethylidae has not been reported yet. In this study, we crystallized into a high-quality chromosome-level genome of ant-like bethylid wasps Sclerodermus sp. ‘alternatusi’ (Hymenoptera: Bethylidae) using PacBio sequencing as well as Hi-C technology. The assembled S. alternatusi genome was 162.30 Mb in size with a contig N50 size of 3.83 Mb and scaffold N50 size of 11.10 Mb. Totally, 92.85% assembled sequences anchored to 15 pseudo-chromosomes. A total of 10,204 protein-coding genes were annotated, and 23.01 Mb repetitive sequences occupying 14.17% of genome were pinpointed. The BUSCO results showed that 97.9% of the complete core Insecta genes were identified in the genome, while 97.1% in the gene sets. The high-quality genome of S. alternatusi will not only provide valuable genomic information, but also show insights into parasitoid wasp evolution and bio-control application in future studies.
Unveiling allelopathic dynamics and impacts of invasive Erigeron bonariensis and Bidens pilosa on plant communities and soil parameters
Authors: Balah Mohamed A. , Al-Andal Abeer , Radwan Asmaa M. , Donia Abd ElRaheim M. 
Published: May 2024

AbstractInvasive alien species are becoming more and more prevalent worldwide,Erigeron bonariensisandBidens pilosaare two invasive species of Asteraceae in Egypt. To mitigate their detrimental effects and understand their differences in invasiveness, we compared the allelopathic potentials ofE. bonariensisandB. pilosausing leachates, decaying residues, and volatilization processes. Notably, the allelopathic variances in leachates were significant, influenced by plant types, concentrations, and response patterns of target plant traits, as indicated by EC50. The relative phytotoxicity of the invasive species decayed residues peaked between 20 and 25 days in the soil, with a positive correlation with concentrations and soil properties. The highest quantities of phenolic acids were chlorogenic acid and caffeic acid reaching (5.41 and 4.39 µg g−1)E. bonariensisand (4.53 and 4.46 µg g−1)B. pilosa, in leachates extracts respectively, while in the soil extract of decayed residues were coumaric acid and ferulic acid measuring (1.66 and 1.67 µg g−1)E. bonariensisand (1.47 and 1.57 µg g−1)B. pilosa, respectively. Using GC/MS analysis, the main volatile components inE. bonariensiswere 1, 8 cineole (5.62%), and α-terpinene (5.43%) and iso-Caryophyllene (5.2%) which showed the greatest inhibitory effects. While B. pilosamain constituents were trans-sabinene (5.39%) and Camphene (5.11%), respectively. Finally, the high invasion level displayed fromE. bonariensis(0.221) compared withB. pilosa(0.094) which correlated with the stronger allelopathic activities against plant species, and soil properties. Therefore, the allelopathic potentialities of these species are critically relevant to their invasion success.
Dynamics of somatostatin 4 receptor expression during chronic-stress loading and its potential as a chronic-stress marker
Authors: Abe Yuki , Murase Takehiko , Mitsuma Masahide , Shinba Yoriko , Yamashita Hiromi , Ikematsu Kazuya 
Published: May 2024

AbstractChronic stress has been implicated in mental illnesses and depressive behaviors. Somatostatin 4 receptor (SSTR4) has been shown to mediate anxiolytic and depression-like effects. Here, we aimed to explore the potential of SSTR4 as a diagnostic marker for chronic stress in mice. The mice were divided into single stress, chronic restraint stress, and control groups, and Sstr4 mRNA expression in the pituitary, lungs, and thymus, its protein expression in the thymus, were analyzed. Compared to controls, Sstr4 mRNA expression decreased significantly in the pituitary gland of the chronic and single-stress groups (P = 0.0181 and 0.0022, respectively) and lungs of the single-stress group (P = 0.0124), whereas it significantly increased in the thymus of the chronic-stress group (P = 0.0313). Thymic SSTR4 expression did not decrease significantly in stress groups compared to that in the control group (P = 0.0963). These results suggest that SSTR4 expression fluctuates in response to stress. Furthermore, Sstr4 mRNA expression dynamics in each organ differed based on single or chronic restraint stress-loading periods. In conclusion, this study suggests that investigating SSTR4 expression in each organ could allow for its use as a stress marker to estimate the stress-loading period and aid in diagnosing chronic stress.
Active self-treatment of a facial wound with a biologically active plant by a male Sumatran orangutan
Authors: Laumer Isabelle B. , Rahman Arif , Rahmaeti Tri , Azhari Ulil , Hermansyah  , Atmoko Sri Suci Utami , Schuppli Caroline 
Published: May 2024

AbstractAlthough self-medication in non-human animals is often difficult to document systematically due to the difficulty of predicting its occurrence, there is widespread evidence of such behaviors as whole leaf swallowing, bitter pith chewing, and fur rubbing in African great apes, orangutans, white handed gibbons, and several other species of monkeys in Africa, Central and South America and Madagascar. To the best of our knowledge, there is only one report of active wound treatment in non-human animals, namely in chimpanzees. We observed a male Sumatran orangutan (Pongo abelii) who sustained a facial wound. Three days after the injury he selectively ripped off leaves of a liana with the common name Akar Kuning (Fibraurea tinctoria), chewed on them, and then repeatedly applied the resulting juice onto the facial wound. As a last step, he fully covered the wound with the chewed leaves. Found in tropical forests of Southeast Asia, this and related liana species are known for their analgesic, antipyretic, and diuretic effects and are used in traditional medicine to treat various diseases, such as dysentery, diabetes, and malaria. Previous analyses of plant chemical compounds show the presence of furanoditerpenoids and protoberberine alkaloids, which are known to have antibacterial, anti-inflammatory, anti-fungal, antioxidant, and other biological activities of relevance to wound healing. This possibly innovative behavior presents the first systematically documented case of active wound treatment with a plant species know to contain biologically active substances by a wild animal and provides new insights into the origins of human wound care.
Atmosphere particulate matter and respiratory diseases during COVID-19 in Korea
Authors: Hong Ji Young , Bang Taemo , Kim Sun Bean , Hong Minwoo , Jung Jaehun 
Published: May 2024

AbstractWe aimed to examine the impact of COVID-19 non-pharmaceutical interventions (NPIs) on the relationship between air pollutants and hospital admissions for respiratory and non-respiratory diseases in six metropolitan cities in South Korea. This study compared the associations between particulate matter (PM10and PM2.5) and hospital admission for respiratory and non-respiratory diseases before (2016–2019) and during (2020) the implementation of COVID-19 NPIs by using distributed lag non-linear models. In the Pre-COVID-19 period, the association between PM10and admission risk for asthma and COPD showed an inverted U-shaped pattern. For PM2.5, S-shaped and inverted U-shaped changes were observed in asthma and COPD, respectively. Extremely high and low levels of PM10and extremely low levels of PM2.5significantly decreased the risk of admission for asthma and COPD. In the Post-COVID-19 outbreak period, the overall cumulative relationship between PM10and PM2.5and respiratory diseases and the effects of extreme levels of PM10and PM2.5on respiratory diseases were completely changed. For non-respiratory diseases, PM10and PM2.5were statistically insignificant for admission risk during both periods. Our study may provide evidence that implementing NPIs and reducing PM10and PM2.5exposure during the COVID-19 pandemic has contributed to reducing hospital admissions for environment-based respiratory diseases.
Expression of Fascin-1 and its diagnostic value in liver cancer
Authors: Lu Shi-Ping , Jiang Li-Jing , Wang Yan , Shao Jun-Kang , Du Zhi-Qun , Huang Bi-Fei , Wang Chao-Qun 
Published: May 2024

AbstractAlthough some studies have reported on the expression and clinical significance of Fascin-1 (FSCN1) in liver cancer, the clinical application and differential diagnosis value of FSCN1 in liver cancer are still unclear. The aim of this study was to analyze the expression level of FSCN1 protein in liver cancer tissues and explore its diagnostic and application value in differentiating between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The immunehistochemical analysis was used to detect the expression of FSCN1 in 108 cases of HCC, 26 cases of ICC, 23 cases of liver cirrhosis, and 11 cases of normal liver tissues. The differences in the positive expression rate and strong positive expression rate of FSCN1 among different groups were analyzed. The positive rate of FSCN1 in normal liver tissues, liver cirrhosis, HCC, and ICC tissues was 0.0% (0/11), 0.0% (0/23), 13.9% (15/108), and 92.3% (24/26), respectively, while the strong positive rate was 0.0% (0/11), 0.0% (0/23), 0.9% (1/108), and 69.2% (18/26), respectively. Both the positive rate and strong positive rate of FSCN1 in ICC tissues were significantly higher than those in HCC, liver cirrhosis, and normal liver tissues. Additionally, the positive rate of FSCN1 in moderately to poorly differentiated HCC tissues was 18.8% (15/80), significantly higher than in well-differentiated HCC (0.0%, 0/28) (P = 0.031). In liver cancer, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FSCN1 positive prediction for ICC were 92.3%, 86.1%, 61.5%, and 97.9%, respectively, whereas the sensitivity, specificity, PPV, and NPV of FSCN1 strong positive prediction for ICC were 69.2%, 99.1%, 94.7%, and 93.0%, respectively. These results suggest that FSCN1 may play an important role in the occurrence and progression of liver cancer, and it can be used as a novel diagnostic marker for ICC.
Epidemiology, treatment and outcomes of primary renal sarcomas in adult patients
Authors: Uhlig Johannes , Uhlig Annemarie , Deshpande Hari , Ströbel Philipp , Trojan Lutz , Lotz Joachim , Hurwitz Michael , Hafez Omeed , Humphrey Peter , Grünwald Viktor , Kim Hyun S. 
Published: May 2024

AbstractTo assess epidemiology, clinical presentation, treatment and overall survival of adult patients with renal sarcomas, the 2004–2016 SEER and NCDB databases were queried for adult patients diagnosed with renal sarcoma, calculating average annual age-adjusted incidence rates (AAIR) and average annual percentage change (AAPC) as well as overall survival (OS). In n = 1279 included renal sarcoma patients, AAIR remained constant over the study period (average 0.53 cases/1million; AAPC = 0.7, p = 0.6). Leiomyosarcoma (AAIR 0.14 cases/1 million) and malignant rhabdoid tumors (0.06 cases/1 million) were most common. Sarcoma histiotypes demonstrated considerable heterogeneity regarding demographic and cancer-related variables. Patients presented with advanced local extent (T3 33.3%; T4 14.2%) or distant metastases (29.1%) and commonly underwent surgical resection (81.6%). Longer OS was independently associated with younger age, female sex, lower comorbidity index, low T stage, negative surgical margins, absence of tumor necrosis or distant metastases and leiomyosarcoma histiotype (multivariable p < 0.05 each). Treatment efficacy varied according to sarcoma histiotype (interaction p < 0.001). Accounting for 0.25% of renal malignancies, renal sarcomas include 43 histiotypes with distinct epidemiology, clinical presentation, outcomes and sensitivity to systemic therapy, thereby reflecting soft-tissue sarcoma behavior. Renal sarcoma treatment patterns follow recommendations by renal cancer guidelines with surgical resection as the cornerstone of therapy.
Copper-based grape pest management has impacted wine aroma
Authors: De Guidi Irene , Galeote Virginie , Blondin Bruno , Legras Jean-Luc 
Published: May 2024

AbstractDespite the high energetic cost of the reduction of sulfate to H2S, required for the synthesis of sulfur-containing amino acids, some wine Saccharomyces cerevisiae strains have been reported to produce excessive amounts of H2S during alcoholic fermentation, which is detrimental to wine quality. Surprisingly, in the presence of sulfite, used as a preservative, wine strains produce more H2S than wild (oak) or wine velum (flor) isolates during fermentation. Since copper resistance caused by the amplification of the sulfur rich protein Cup1p is a specific adaptation trait of wine strains, we analyzed the link between copper resistance mechanism, sulfur metabolism and H2S production. We show that a higher content of copper in the must increases the production of H2S, and that SO2 increases the resistance to copper. Using a set of 51 strains we observed a positive and then negative relation between the number of copies of CUP1 and H2S production during fermentation. This complex pattern could be mimicked using a multicopy plasmid carrying CUP1, confirming the relation between copper resistance and H2S production. The massive use of copper for vine sanitary management has led to the selection of resistant strains at the cost of a metabolic tradeoff: the overproduction of H2S, resulting in a decrease in wine quality.
A new suite of reporter vectors and a novel landing site survey system to study cis-regulatory elements in diverse insect species
Authors: Deem Kevin D. , Halfon Marc S. , Tomoyasu Yoshinori 
Published: May 2024

AbstractComparative analyses between traditional model organisms, such as the fruit fly Drosophila melanogaster, and more recent model organisms, such as the red flour beetle Tribolium castaneum, have provided a wealth of insight into conserved and diverged aspects of gene regulation. While the study of trans-regulatory components is relatively straightforward, the study of cis-regulatory elements (CREs, or enhancers) remains challenging outside of Drosophila. A central component of this challenge has been finding a core promoter suitable for enhancer-reporter assays in diverse insect species. Previously, we demonstrated that a Drosophila Synthetic Core Promoter (DSCP) functions in a cross-species manner in Drosophila and Tribolium. Given the over 300 million years of divergence between the Diptera and Coleoptera, we reasoned that DSCP-based reporter constructs will be useful when studying cis-regulation in a variety of insect models across the holometabola and possibly beyond. To this end, we sought to create a suite of new DSCP-based reporter vectors, leveraging dual compatibility with piggyBac and PhiC31-integration, the 3xP3 universal eye marker, GATEWAY cloning, different colors of reporters and markers, as well as Gal4-UAS binary expression. While all constructs functioned properly with a Tc-nub enhancer in Drosophila, complications arose with tissue-specific Gal4-UAS binary expression in Tribolium. Nevertheless, the functionality of these constructs across multiple holometabolous orders suggests a high potential compatibility with a variety of other insects. In addition, we present the piggyLANDR (piggyBac-LoxP AttP Neutralizable Destination Reporter) platform for the establishment of proper PhiC31 landing sites free from position effects. As a proof-of-principle, we demonstrated the workflow for piggyLANDR in Drosophila. The potential utility of these tools ranges from molecular biology research to pest and disease-vector management, and will help advance the study of gene regulation beyond traditional insect models.
Mitochondrial SIRT3 as a protective factor against cyclosporine A-induced nephrotoxicity
Authors: Kim Ji Eun , Jo Min Jee , Bae So Yeon , Ahn Shin Young , Ko Gang Jee , Kwon Young Joo 
Published: May 2024

AbstractSirtuin3 (SIRT3), a mitochondrial deacetylase, has been shown to be involved in various kidney diseases. In this study, we aimed to clarify the role of SIRT3 in cyclosporine-induced nephrotoxicity and the associated mitochondrial dysfunction. Madin-Darby canine kidney (MDCK) cells were transfected with Flag-tagged SIRT3 for SIRT3 overexpression or SIRT3 siRNA for the inhibition of SIRT3. Subsequently, the cells were treated with cyclosporine A (CsA) or vehicle. Wild-type and SIRT3 knockout (KO) mice were randomly assigned to receive cyclosporine A or olive oil. Furthermore, SIRT3 activator, honokiol, was treated alongside CsA to wild type mice. Our results revealed that CsA treatment inhibited mitochondrial SIRT3 expression in MDCK cells. Inhibition of SIRT3 through siRNA transfection exacerbated apoptosis, impaired the expression of the AMP-activated protein kinase-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK-PGC1α) pathway, and worsened mitochondrial dysfunction induced by CsA treatment. Conversely, overexpression of SIRT3 through Flag-tagged SIRT3 transfection ameliorated apoptosis, increased the expression of mitochondrial superoxide dismutase 2, and restored the mitochondrial regulator pathway, AMPK-PGC1α. In SIRT3 KO mice, CsA treatment led to aggravated kidney dysfunction, increased kidney tubular injury, and accumulation of oxidative end products indicative of oxidative stress injury. Meanwhile, SIRT3 activation in vivo significantly mitigated these adverse effects, improving kidney function, reducing oxidative stress markers, and enhancing mitochondrial health following CsA treatment. Overall, our findings suggest that SIRT3 plays a protective role in alleviating mitochondrial dysfunction caused by CsA through the activation of the AMPK-PGC1α pathway, thereby preventing further kidney injury.
Predictors of social risk for post-ischemic stroke reintegration
Authors: Cisek Katryna K. , Nguyen Thi Nguyet Que , Garcia-Rudolph Alejandro , Saurí Joan , Becerra Martinez Helard , Hines Andrew , Kelleher John D. 
Published: May 2024

AbstractAfter stroke rehabilitation, patients need to reintegrate back into their daily life, workplace and society. Reintegration involves complex processes depending on age, sex, stroke severity, cognitive, physical, as well as socioeconomic factors that impact long-term outcomes post-stroke. Moreover, post-stroke quality of life can be impacted by social risks of inadequate family, social, economic, housing and other supports needed by the patients. Social risks and barriers to successful reintegration are poorly understood yet critical for informing clinical or social interventions. Therefore, the aim of this work is to predict social risk at rehabilitation discharge using sociodemographic and clinical variables at rehabilitation admission and identify factors that contribute to this risk. A Gradient Boosting modelling methodology based on decision trees was applied to a Catalan 217-patient cohort of mostly young (mean age 52.7), male (66.4%), ischemic stroke survivors. The modelling task was to predict an individual’s social risk upon discharge from rehabilitation based on 16 different demographic, diagnostic and social risk variables (family support, social support, economic status, cohabitation and home accessibility at admission). To correct for imbalance in patient sample numbers with high and low-risk levels (prediction target), five different datasets were prepared by varying the data subsampling methodology. For each of the five datasets a prediction model was trained and the analysis involves a comparison across these models. The training and validation results indicated that the models corrected for prediction target imbalance have similarly good performance (AUC 0.831–0.843) and validation (AUC 0.881 - 0.909). Furthermore, predictor variable importance ranked social support and economic status as the most important variables with the greatest contribution to social risk prediction, however, sex and age had a lesser, but still important, contribution. Due to the complex and multifactorial nature of social risk, factors in combination, including social support and economic status, drive social risk for individuals.