bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the novel GLAS algorithm as an aid in the detection of liver fibrosis and cirrhosis based on GP73, LG2m, age, and sex
Authors: Hemken Philip M. , Qin Xuzhen , Sokoll Lori J. , Jackson Laurel , Feng Fan , Li Peng , Gawel Susan H. , Tu Bailin , Lin Zhihong , Hartnett James , Hawksworth David , Tieman Bryan C. , Yoshimura Toru , Kinukawa Hideki , Ning Shaohua , Liu Enfu , Meng Fanju , Chen Fei , Miao Juru , Mi Xuan , Tong Xin , Chan Daniel W. , Davis Gerard J. 
Published: November 2023

AbstractBackgroundDiagnosis of liver disease at earlier stages can improve outcomes and reduce the risk of progression to malignancy. Liver biopsy is the gold standard for diagnosis of liver disease, but is invasive and sample acquisition errors are common. Serum biomarkers for liver function and fibrosis, combined with patient factors, may allow for noninvasive detection of liver disease. In this pilot study, we tested and validated the performance of an algorithm that combines GP73 and LG2m serum biomarkers with age and sex (GLAS) to differentiate between patients with liver disease and healthy individuals in two independent cohorts.MethodsTo develop the algorithm, prototype immunoassays were used to measure GP73 and LG2m in residual serum samples collected between 2003 and 2016 from patients with staged fibrosis and cirrhosis of viral or non-viral etiology (n = 260) and healthy subjects (n = 133). The performance of five predictive models using combinations of age, sex, GP73, and/or LG2m from the development cohort were tested. Residual samples from a separate cohort with liver disease (fibrosis, cirrhosis, or chronic liver disease;n = 395) and healthy subjects (n = 106) were used to validate the best performing model.ResultsGP73 and LG2m concentrations were higher in patients with liver disease than healthy controls and higher in those with cirrhosis than fibrosis in both the development and validation cohorts. The best performing model included both GP73 and LG2m plus age and sex (GLAS algorithm), which had an AUC of 0.92 (95% CI: 0.90–0.95), a sensitivity of 88.8%, and a specificity of 75.9%. In the validation cohort, the GLAS algorithm had an estimated an AUC of 0.93 (95% CI: 0.90–0.95), a sensitivity of 91.1%, and a specificity of 80.2%. In both cohorts, the GLAS algorithm had high predictive probability for distinguishing between patients with liver disease versus healthy controls.ConclusionsGP73 and LG2m serum biomarkers, when combined with age and sex (GLAS algorithm), showed high sensitivity and specificity for detection of liver disease in two independent cohorts. The GLAS algorithm will need to be validated and refined in larger cohorts and tested in longitudinal studies for differentiating between stable versus advancing liver disease over time.
D-allose Inhibits TLR4/PI3K/AKT Signaling to Attenuate Neuroinflammation and Neuronal Apoptosis by Inhibiting Gal-3 Following Ischemic Stroke
Authors: Luo Yaowen , Cheng Junkai , Fu Yihao , Zhang Min , Gou Maorong , Li Juan , Li Xiaobing , Bai Jing , Zhou Yuefei , Zhang Lei , Gao Dakuan 
Published: November 2023

Abstract
Background
Ischemic stroke (IS) occurs when a blood vessel supplying the brain becomes obstructed, resulting in cerebral ischemia. This type of stroke accounts for approximately 87% of all strokes. Globally, IS leads to high mortality and poor prognosis and is associated with neuroinflammation and neuronal apoptosis. D-allose is a bio-substrate of glucose that is widely expressed in many plants. Our previous study showed that D-allose exerted neuroprotective effects against acute cerebral ischemic/reperfusion (I/R) injury by reducing neuroinflammation. Here, we aimed to clarify the beneficial effects D-allose in suppressing IS-induced neuroinflammation damage, cytotoxicity, neuronal apoptosis and neurological deficits and the underlying mechanism in vitro and in vivo.

Methods
In vivo, an I/R model was induced by middle cerebral artery occlusion and reperfusion (MCAO/R) in C57BL/6 N mice, and D-allose was given by intraperitoneal injection within 5 min after reperfusion. In vitro, mouse hippocampal neuronal cells (HT-22) with oxygen–glucose deprivation and reperfusion (OGD/R) were established as a cell model of IS. Neurological scores, some cytokines, cytotoxicity and apoptosis in the brain and cell lines were measured. Moreover, Gal-3 short hairpin RNAs, lentiviruses and adeno-associated viruses were used to modulate Gal-3 expression in neurons in vitro and in vivo to reveal the molecular mechanism.

Results
D-allose alleviated cytotoxicity, including cell viability, LDH release and apoptosis, in HT-22 cells after OGD/R, which also alleviated brain injury, as indicated by lesion volume, brain edema, neuronal apoptosis, and neurological functional deficits, in a mouse model of I/R. Moreover, D-allose decreased the release of inflammatory factors, such as IL-1β, IL-6 and TNF-α. Furthermore, the expression of Gal-3 was increased by I/R in wild-type mice and HT-22 cells, and this factor further bound to TLR4, as confirmed by three-dimensional structure prediction and Co-IP. Silencing the Gal-3 gene with shRNAs decreased the activation of TLR4 signaling and alleviated IS-induced neuroinflammation, apoptosis and brain injury. Importantly, the loss of Gal-3 enhanced the D-allose-mediated protection against I/R-induced HT-22 cell injury, inflammatory insults and apoptosis, whereas activation of TLR4 by the selective agonist LPS increased the degree of neuronal injury and abolished the protective effects of D-allose.

Conclusions
In summary, D-allose plays a crucial role in inhibiting inflammation after IS by suppressing Gal-3/TLR4/PI3K/AKT signaling pathway in vitro and in vivo.
The impact of lower caseloads in public employment services on the unemployed
Authors: Böheim René , Eppel Rainer , Mahringer Helmut 
Published: November 2023

AbstractIn a randomised controlled trial in Austria, lowering caseloads for caseworkers in a Public Employment Office led to more meetings with unemployed clients, more job offers, more programme assignments, and more sanctions for noncompliance with job search requirements. It shortened unemployment spells through faster job entry, but also through more exits from the labour force in the 2 years following treatment. The duration of unemployment was reduced for a number of subgroups of the unemployed, but not all benefited from increased employment. For women and foreigners, lower caseloads led to more time out of the labour force. The quality of jobs after unemployment, measured by wages, did not change. A cost–benefit analysis suggests that lower caseloads not only shorten unemployment but also save public costs.
Sequenced-based GWAS for linear classification traits in Belgian Blue beef cattle reveals new coding variants in genes regulating body size in mammals
Authors: Gualdrón Duarte José Luis , Yuan Can , Gori Ann-Stephan , Moreira Gabriel C. M. , Takeda Haruko , Coppieters Wouter , Charlier Carole , Georges Michel , Druet Tom 
Published: November 2023

Abstract
Background
Cohorts of individuals that have been genotyped and phenotyped for genomic selection programs offer the opportunity to better understand genetic variation associated with complex traits. Here, we performed an association study for traits related to body size and muscular development in intensively selected beef cattle. We leveraged multiple trait information to refine and interpret the significant associations.

Results
After a multiple-step genotype imputation to the sequence-level for 14,762 Belgian Blue beef (BBB) cows, we performed a genome-wide association study (GWAS) for 11 traits related to muscular development and body size. The 37 identified genome-wide significant quantitative trait loci (QTL) could be condensed in 11 unique QTL regions based on their position. Evidence for pleiotropic effects was found in most of these regions (e.g., correlated association signals, overlap between credible sets (CS) of candidate variants). Thus, we applied a multiple-trait approach to combine information from different traits to refine the CS. In several QTL regions, we identified strong candidate genes known to be related to growth and height in other species such as LCORL-NCAPG or CCND2. For some of these genes, relevant candidate variants were identified in the CS, including three new missense variants in EZH2, PAPPA2 and ADAM12, possibly two additional coding variants in LCORL, and candidate regulatory variants linked to CCND2 and ARMC12. Strikingly, four other QTL regions associated with dimension or muscular development traits were related to five (recessive) deleterious coding variants previously identified.

Conclusions
Our study further supports that a set of common genes controls body size across mammalian species. In particular, we added new genes to the list of those associated with height in both humans and cattle. We also identified new strong candidate causal variants in some of these genes, strengthening the evidence of their causality. Several breed-specific recessive deleterious variants were identified in our QTL regions, probably as a result of the extreme selection for muscular development in BBB cattle.
Identification of HpMYB1 inducing anthocyanin accumulation in Hippeastrum Hybridum tepals by RNA-seq
Authors: Li Ji , Wu Kunlin , Li Lin , Ma Guohua , Fang Lin , Zeng Songjun 
Published: November 2023

Abstract
Background
Cultivated Hippeastrum × hybridum is a popular ornamental plant with large and colorful flowers, long flowering duration, and high commercial value. As its main ornamental feature, its flower color is related to the anthocyanin content in the tepals. However, the molecular regulatory mechanisms of anthocyanin biosynthesis in H. × hybridum have not yet been elucidated.

Results
In the present study, 12 cDNA libraries of four stages of H.× hybridum ‘Royal Velvet’ tepal development were used for RNA-seq, obtaining 79.83 gigabases (GB) of clean data. The data were assembled into 148,453 unigenes, and 11,262 differentially expressed genes were identified. Forty key enzymes participating in anthocyanin biosynthesis were investigated, and the results showed that most of the anthocyanin structural genes were expressed at low levels in S1 and were markedly upregulated in S2 and S3. The expression profiles of 12 selected genes were verified by qRT-PCR. Furthermore, the R2R3-MYB transcription factor (TF), HpMYB1, involved in the regulation of anthocyanin biosynthesis was identified by sequence, expression pattern, and subcellular localization analyses. Its overexpression in tobacco significantly increased the anthocyanin levels in various tissues and activated anthocyanin-related genes.

Conclusions
Using RNA-seq technology, we successfully identified a potential R2R3-MYB gene, HpMYB1, that regulates anthocyanin biosynthesis in H.× hybridum ‘Royal Velvet’. Our findings provide basic transcript information and valuable transcriptome data for further identification of key genes involved in anthocyanin biosynthesis and can be applied in the artificial breeding of new H. × hybridum cultivars with enhanced ornamental value.
Endoscopic and histopathological hints on infections in patients of common variable immunodeficiency disorder with gastrointestinal symptoms
Authors: Chen Yang , You Yan , Li Ji , Yang Aiming , Zhou Weixun , Li Xiaoqing 
Published: November 2023

Abstract
Background and aims
Common variable immunodeficiency disorder (CVID) patients may have gastrointestinal (GI) involvement and suffer from infections, which are poorly understood. This study aimed to evaluate the clinical, endoscopic, and histopathological features of CVID patients with GI symptoms and determine their correlation with infections.

Methods
We performed a retrospective study on 21 CVID patients with GI symptoms who underwent endoscopic examination in Peking Union Medical College Hospital from 2000 to 2020. The clinical, infectious, endoscopic, and histopathological features were reassessed.

Results
Chronic diarrhea was the most prevalent GI symptom, observed in 95.2% of our CVID cohort. Over 85% of patients had low body weight and malabsorption. Small bowel villous atrophy was found in 90.5% of patients under endoscopy and mostly confirmed by histopathology. GI infections were identified in 9 (42.9%) patients. Of these, 7 patients with diffuse and obvious nodular lymphoid hyperplasia (NLH) of small bowel under endoscopy had significantly higher infection rate (85.7% vs 21.4%, p < 0.05), predominantly with Giardia and bacteria. Small bowel biopsies showed 95% of patients lacked plasma cells and 60% had increased intraepithelial lymphocytes (IELs), but not significantly different between GI infection and non-infection group. Most patients improved after intravenous immunoglobulin and anti-infection therapy.

Conclusions
CVID could involve GI tract, particularly small bowel. Obvious NLH under endoscopy could be a hint for GI infection in CVID patients. Comprehensive endoscopic and histopathological evaluation may be helpful in CVID diagnosis and identification of potential co-infection, leading to proper treatment.
A rapid review of antenatal hepatitis C virus testing in the United Kingdom
Authors: Hibbert M. P. , Simmons R. , Mandal S. , Sabin C. A. , Desai M. 
Published: November 2023

Abstract
Background
The United Kingdom (UK) has committed to the World Health Organization’s viral hepatitis elimination targets. New case finding strategies, such as antenatal testing, may be needed to achieve these targets. We conducted a rapid review to understand hepatitis C-specific antibody (anti-HCV) and HCV RNA test positivity in antenatal settings in the United Kingdom to inform guidance.

Methods
Articles and conference abstracts published between January 2000 and June 2022 reporting anti-HCV testing in antenatal settings were identified through PubMed and Web of Science searches. Results were synthesised using a narrative approach.

Results
The search identified 2,011 publications; 10 studies were included in the final synthesis. Seven studies used anonymous testing methods and three studies used universal opt-out testing. Anti-HCV test positivity ranged from 0.1 to 0.99%, with a median value of 0.38%. Five studies reported HCV RNA positivity, which ranged from 0.1 to 0.57% of the testing population, with a median value of 0.22%. One study reported cost effectiveness of HCV and found it to be cost effective at £9,139 per quality adjusted life years.

Conclusion
The relative contribution of universal opt-out antenatal testing for HCV should be reconsidered, as antenatal testing could play an important role in new case-finding and aid achieving elimination targets.
TIGIT+ NK cells in combination with specific gut microbiota features predict response to checkpoint inhibitor therapy in melanoma patients
Authors: Tsakmaklis Anastasia , Farowski Fedja , Zenner Rafael , Lesker Till Robin , Strowig Till , Schlößer Hans , Lehmann Jonas , von Bergwelt-Baildon Michael , Mauch Cornelia , Schlaak Max , Knuever Jana , Schweinsberg Viola , Heinzerling Lucie M. , Vehreschild Maria J. G. T. 
Published: November 2023

Abstract
Background
Composition of the intestinal microbiota has been correlated to therapeutic efficacy of immune checkpoint inhibitors (ICI) in various cancer entities including melanoma. Prediction of the outcome of such therapy, however, is still unavailable. This prospective, non-interventional study was conducted in order to achieve an integrated assessment of the connection between a specific intestinal microbiota profile and antitumor immune response to immune checkpoint inhibitor therapy (anti-PD-1 and/or anti-CTLA-4) in melanoma patients.

Methods
We assessed blood and stool samples of 29 cutaneous melanoma patients who received immune checkpoint inhibitor therapy. For functional and phenotypical immune analysis, 12-color flow cytometry and FluoroSpot assays were conducted. Gut microbiome was analyzed with shotgun metagenomics sequencing. To combine clinical, microbiome and immune variables, we applied the Random Forest algorithm.

Results
A total of 29 patients was analyzed in this study, among whom 51.7% (n = 15) reached a durable clinical benefit. The Immune receptor TIGIT is significantly upregulated in T cells (p = 0.0139) and CD56high NK cells (p = 0.0037) of responders. Several bacterial taxa were associated with response (e.g. Ruminococcus torques) or failure (e.g. Barnesiella intestinihominis) to immune therapy. A combination of two microbiome features (Barnesiella intestinihominis and the Enterobacteriaceae family) and one immune feature (TIGIT+ CD56high NK cells) was able to predict response to ICI already at baseline (AUC = 0.85; 95% CI: 0.841–0.853).

Conclusions
Our results reconfirm a link between intestinal microbiota and response to ICI therapy in melanoma patients and furthermore point to TIGIT as a promising target for future immunotherapies.
Higher global diet quality score is related to lower prevalence of depression and poor quality of life among adolescent girls
Authors: Beigrezaei Sara , Darabi Zahra , Davies Ian G. , Mazidi Mohsen , Ghayour-Mobarhan Majid , Khayyatzadeh Sayyed Saeid 
Published: November 2023

Abstract
Background
Adolescence is a key time for the development of depression symptoms and the diet quality may be associated with mental health conditions. The present study examined the association between depression and quality of life (QoL) and the global diet quality score (GDQS) as a simple and standardized metric diet quality in Iranian adolescents.

Methods
This cross-sectional study was conducted on 733 adolescent girls recruited using a random cluster sampling method. A 147-item food frequency questionnaire (FFQ) was used for dietary intake assessment. The GDQS is gained by summing points of all the 25 food groups, ranged from 0 to 49. Depression symptoms were assessed using a Persian version of the Beck Depression Inventory (BDI). For assessment of health-related QoL, the Short Form 12 Survey–version 2 (SF-12v2) questionnaire was employed. Multivariable logistic regression examined the association of depression and QoL with GDQS in crude and adjusted models.

Results
Adolescent girls in the highest tertile of GDQS score compared with the lowest tertile had a 41% lower odds of depressive symptoms (OR: 0.59; 95% CI: 0.39–0.90, P = 0.01). The participants in the third tertile of GDQS score had lower odds of poor QoL compared with the first tertile (OR: 0.56; 95% CI: 0.37–0.85, P < 0.01). These associations remained significant (both P = 0.01) after adjustment for age, energy intake, body mass index (BMI), physical activity, and menstruation (depressive symptoms: OR: 0.59; 95% CI: 0.38–0.92; QoL: OR: 0.59; 95% CI: 0.38–0.91, P = 0.01).

Conclusion
We found that adolescent girls with a higher score of the GDQS had lower odds of depression and poor QoL Prospective and interventional investigations are needed to reach a clear vision.
Understanding COVID-19 vaccine hesitancy in the Hispanic adult population of South Carolina: a complex mixed-method design evaluation study
Authors: Rossi Maria Mercedes , Parisi Michelle A. , Cartmell Kathleen B. , McFall Danielle 
Published: November 2023

AbstractBackgroundIn August 2021, only 47.6% of all eligible residents in South Carolina (SC) had received at least one dose of the COVID-19 vaccine, with only 41% having completed their vaccination series. Additionally, only 27% of all Hispanics in SC had completed their vaccination series compared to 34.1% of non-Hispanics. Vaccine hesitancy is a complex phenomenon that is context and vaccine-specific. Focusing on unvaccinated Hispanics living in rural areas of SC, this study aimed to identify barriers to vaccination and provide an educational intervention designed to address vaccine hesitancy.MethodsA complex mixed-methods evaluation design was used to conduct this study. First, in-person vaccine educational sessions were implemented, along with a pre-post-test survey, to assess changes in knowledge, attitudes, motivations, barriers, and intentions to receive COVID-19 vaccination. Second, in-person follow-up focus groups were held with the same participants to gather in-depth insight about participants’ knowledge and attitudes about the COVID-19 vaccination. Third, an online follow-up survey was conducted to assess the effect of the training and discussion session on COVID-19 vaccination. Study outcomes were assessed among the 17 individuals who participated in the educational sessions and focus group discussions.ResultsFindings revealed that for unvaccinated Hispanics living in South Carolina; vaccine hesitancy was primarily driven by: 1) misinformation and information coming from unverified sources and 2) negative perceptions of the safety and effectiveness of the COVID-19 vaccines. Specifically, participants were fearful that the vaccine development was rushed and that the vaccines might contain questionable ingredients that could cause strong side effects or even death. Participants were also concerned that vaccination might cause them to get sick and be hospitalized, which would have financial implications since they could not afford healthcare or take time off work.ConclusionsProgram implementation and mass communication campaigns should focus on COVID-19 vaccine safety and effectiveness, including side effects, what to expect after being vaccinated, and how to look for information from reputable sources. The educational session implemented proved to be effective and helped reduce vaccine hesitancy since most participants (80%) self-reported receiving a COVID-19 vaccine after program participation.
Using intra-breath oscillometry in obesity hypoventilation syndrome to detect tidal expiratory flow limitation: a potential marker to optimize CPAP therapy
Authors: Baglyas Szabolcs , Valkó Luca , Móró Vivien , Podmaniczky Eszter , Czövek Dorottya , Makan Gergely , Gingl Zoltán , Gál János , Hantos Zoltán , Lorx András 
Published: November 2023

Abstract
Background
Continuous positive airway pressure (CPAP) therapy has profound effects in obesity hypoventilation syndrome (OHS). Current therapy initiation focuses on upper airway patency rather than the assessment of altered respiratory mechanics due to increased extrapulmonary mechanical load.

Methods
We aimed to examine the viability of intra-breath oscillometry in optimizing CPAP therapy for OHS. We performed intra-breath oscillometry at 10 Hz in the sitting and supine positions, followed by measurements at increasing CPAP levels (none-5-10-15-20 cmH2O) in awake OHS patients. We plotted intra-breath resistance and reactance (Xrs) values against flow (V’) and volume (V) to identify tidal expiratory flow limitation (tEFL).

Results
Thirty-five patients (65.7% male) completed the study. We found a characteristic looping of the Xrs vs V’ plot in all patients in the supine position revealing tEFL: Xrs fell with decreasing flow at end-expiration. Intra-breath variables representing expiratory decrease of Xrs became more negative in the supine position [end-expiratory Xrs (mean ± SD): -1.9 ± 1.8 cmH2O·s·L− 1 sitting vs. -4.2 ± 2.2 cmH2O·s·L− 1 supine; difference between end-expiratory and end-inspiratory Xrs: -1.3 ± 1.7 cmH2O·s·L− 1 sitting vs. -3.6 ± 2.0 cmH2O·s·L− 1 supine, p < 0.001]. Increasing CPAP altered expiratory Xrs values and loop areas, suggesting diminished tEFL (p < 0.001). ‘Optimal CPAP’ value (able to cease tEFL) was 14.8 ± 4.1 cmH2O in our cohort, close to the long-term support average of 13.01(± 2.97) cmH2O but not correlated. We found no correlation between forced spirometry values, patient characteristics, apnea-hypopnea index and intra-breath oscillometry variables.

Conclusions
tEFL, worsened by the supine position, can be diminished by stepwise CPAP application in most patients. Intra-breath oscillometry is a viable method to detect tEFL during CPAP initiation in OHS patients and tEFL is a possible target for optimizing therapy in OHS patients.