bluuebunny/crossref_metadata_2025_split huggingface dataset:
IGF-1R targeting in cancer – does sub-cellular localization matter?
Authors: Soni Upendra K. , Jenny Liam , Hegde Rashmi S. 
Published: October 2023

AbstractThe insulin-like growth factor receptor (IGF-1R) was among the most intensively pursued kinase targets in oncology. However, even after a slew of small-molecule and antibody therapeutics reached clinical trials for a range of solid tumors, the initial promise remains unfulfilled. Mechanisms of resistance to, and toxicities resulting from, IGF-1R-targeted drugs are well-catalogued, and there is general appreciation of the fact that a lack of biomarker-based patient stratification was a limitation of previous clinical trials. But no next-generation therapeutic strategies have yet successfully exploited this understanding in the clinic.Currently there is emerging interest in re-visiting IGF-1R targeted therapeutics in combination-treatment protocols with predictive biomarker-driven patient-stratification. One such biomarker that emerged from early clinical trials is the sub-cellular localization of IGF-1R. After providing some background on IGF-1R, its drugging history, and the trials that led to the termination of drug development for this target, we look more deeply into the correlation between sub-cellular localization of IGF-1R and susceptibility to various classes of IGF-1R - targeted agents.
Protocol for a randomised feasibility trial comparing a combined program of education and exercise versus general advice for ankle osteoarthritis
Authors: Smith Michelle D. , Vuvan Viana , Collins Natalie J. , Hunter David J. , Costa Nathalia , Smith Melinda M. Franettovich , Vicenzino Bill 
Published: October 2023

AbstractBackgroundAnkle osteoarthritis (OA) is a serious problem with high associated pain and disability. While education and exercise are recommended for the initial management of OA, this has not been investigated in ankle OA. The primary aim of this study is to establish the feasibility of running a full‐scale randomised controlled trial (RCT) investigating a combined education and exercise program compared to a general advice program for people with ankle OA. The secondary aims are to collect preliminary data which will inform sample size calculations, and understand the perspectives of people with ankle OA on their participation in the trial.MethodsThirty individuals aged 35 years or older with symptomatic radiographic ankle OA will be recruited from the community and randomised to receive either a combined education and exercise program or a general advice program, both of which will be delivered by a physiotherapist in a group setting. Primary outcomes of feasibility include responses to study advertisements, number of eligible participants, recruitment rate, adherence with the intervention, fidelity of the intervention, adverse events, drop‐out rate, and credibility and expectancy of the intervention. Secondary participant‐reported outcomes will include global rating of change, patient acceptable symptom state, severity of ankle pain and stiffness, self‐reported function, quality of life, satisfaction with treatment, and use of co‐interventions. Follow up will be at 8 weeks and 3 months. Physical measures of 40 m walking speed, timed stairs descent, heel raise endurance and ankle dorsiflexion range of motion will be collected at baseline and 8 weeks. Primary feasibility outcomes will be reported descriptively, and estimates of the variability of secondary participant‐reported and physical outcomes will be calculated. Semi‐structured interviews will be conducted with participants to understand perspectives about the intervention and participation in the trial, with data analyzed thematically.DiscussionStudy findings will establish the feasibility of running a full‐scale RCT to investigate a combined education and exercise program compared to a general advice program for people with ankle OA. This study is a necessary first step to advance the international research agenda of evaluating the efficacy of exercise in the management of ankle OA.Trial registrationACTRN12623000017628. Registered 10 January 2023, https://www.anzctr.org.au/ACTRN12623000017628.aspx.
Ten reasons to screen women at risk of lung cancer
Authors: Revel Marie-Pierre , Chassagnon Guillaume 
Published: October 2023

AbstractThis opinion piece reviews major reasons for promoting lung cancer screening in at-risk women who are smokers or ex-smokers, from the age of 50. The epidemiology of lung cancer in European women is extremely worrying, with lung cancer mortality expected to surpass breast cancer mortality in most European countries. There are conflicting data as to whether women are at increased risk of developing lung cancer compared to men who have a similar tobacco exposure. The sharp increase in the incidence of lung cancer in women exceeds the increase in their smoking exposure which is in favor of greater susceptibility. Lung and breast cancer screening could be carried out simultaneously, as the screening ages largely coincide. In addition, lung cancer screening could be carried out every 2 years, as is the case for breast cancer screening, if the baseline CT scan is negative.As well as detecting early curable lung cancer, screening can also detect coronary heart disease and osteoporosis induced by smoking. This enables preventive measures to be taken in addition to smoking cessation assistance, to reduce morbidity and mortality in the female population.Key points• The epidemiology of lung cancer in European women is very worrying.• Lung cancer is becoming the leading cause of cancer mortality in European women.• Women benefit greatly from screening in terms of reduced risk of death from lung cancer.
Farmers’ knowledge of Johne’s disease and opinions of the Irish Johne’s Control Programme: results of an online survey answered mostly by young farmers
Authors: Horan Louise , Mee John F. , Field Niamh L. , Walsh Siobhán W. , Valldecabres Ainhoa 
Published: October 2023

AbstractA voluntary control programme for Johne’s disease, the Irish Johne’s Control Programme (IJCP) has been implemented in Ireland since 2017. The objective of this observational study was to assess Irish beef and dairy farmers’ Johne’s disease knowledge, implemented management practices and IJCP opinions. A questionnaire open to dairy and beef farmers was distributed via social media and email. In total 126 responses were used for this study; these responses came from mostly young farmers (18–25 years old) and represent a small proportion of the total number of dairy and beef farmers in Ireland whose average age is 55.Most respondents claimed to know what Johne’s disease was (73%; 92/126) and associated the disease to loss of body condition (68%; 78/114) and diarrhoea (59%; 67/114). Twenty-eight respondents (mostly dairy farmers; 22/28) reported positive cases in their premises. And 38% reported to implement management practices to prevent Johne’s disease transmission within or into their herd (i.e. management of milk for calf consumption and isolation of Johne’s test-positive or newly purchased stock; 47/124).Eighteen percent (22/125) of respondents were, at the time of questionnaire or previously, members of the IJCP. The main benefits reported by some of the participating farmers were identification of positive cases (29%; 4/14), and management of milk for calf consumption (21%; 3/14). While the main disadvantage was inaccurate testing methods (50%; 10/20). The main reasons reported for the lack of participation in the IJCP were not being aware of the programme (52%; 53/102) and not having a Johne’s disease problem on the farm (48%; 49/102).In conclusion, this study suggests that while young farmers are aware of Johne’s disease, their participation in the IJCP is limited and could benefit from further promotion. Studies representing the wider farming community in Ireland are warranted to gather non-biased input and contribute to Johne’s disease control in Ireland.
The predictive value of machine learning for mortality risk in patients with acute coronary syndromes: a systematic review and meta-analysis
Authors: Zhang Xiaoxiao , Wang Xi , Xu Luxin , Liu Jia , Ren Peng , Wu Huanlin 
Published: October 2023

AbstractBackgroundAcute coronary syndromes (ACS) are the leading cause of global death. Optimizing mortality risk prediction and early identification of high-risk patients is essential for developing targeted prevention strategies. Many researchers have built machine learning (ML) models to predict the mortality risk in ACS patients. Our meta-analysis aimed to evaluate the predictive value of various ML models in predicting death in ACS patients at different times.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched systematically from database establishment to March 12, 2022 for studies developing or validating at least one ML predictive model for death in ACS patients. We used PROBAST to assess the risk of bias in the reported predictive models and a random-effects model to assess the pooled C-index and accuracy of these models.ResultsFifty papers were included, involving 216 ML prediction models, 119 of which were externally validated. The combined C-index of the ML models in the validation cohort predicting the in-hospital mortality, 30-day mortality, 3- or 6-month mortality, and 1 year or above mortality in ACS patients were 0.8633 (95% CI 0.8467–0.8802), 0.8296 (95% CI 0.8134–0.8462), 0.8205 (95% CI 0.7881–0.8541), and 0.8197 (95% CI 0.8042–0.8354), respectively, with the corresponding combined accuracy of 0.8569 (95% CI 0.8411–0.8715), 0.8282 (95% CI 0.7922–0.8591), 0.7303 (95% CI 0.7184–0.7418), and 0.7837 (95% CI 0.7455–0.8175), indicating that the ML models were relatively excellent in predicting ACS mortality at different times. Furthermore, common predictors of death in ML models included age, sex, systolic blood pressure, serum creatinine, Killip class, heart rate, diastolic blood pressure, blood glucose, and hemoglobin.ConclusionsThe ML models had excellent predictive power for mortality in ACS, and the methodologies may need to be addressed before they can be used in clinical practice.
Research progress on the GRP78 gene in the diagnosis, treatment and immunity of cervical cancer
Authors: Bai Yingying , Wang Wenhua , Cheng Yuemei , Yang Yongxiu 
Published: October 2023

AbstractBackgroundGRP78 is a molecular chaperone protein in the endoplasmic reticulum that is involved in protein assembly and quality control, and it participates in ER stress regulation of endoplasmic reticulum stress pathways. Studies have confirmed that GRP78 gene is highly expressed in a variety of tumors and is involved in different biological functions.PurposeThe present review highlights the involvement of the GRP78 gene in regulating the development of cervical cancer by promoting the proliferation and invasion of cervical cancer cells as well as by inhibiting apoptosis and promoting the Warburg effect. High expression of GRP78 is positively correlated with chemotherapy resistance in cervical cancer. GRP78 plays an anticancer role in cervical cancer by regulating autophagy and apoptosis. Mediated immune CD8 + T cells regulate tumor cell immunity and play a role in the application of the HPV vaccine.ConclusionsGRP78 plays a multifunctional role in cervical cancer and has important therapeutic and diagnostic value.
Four functional profiles for fibre and mucin metabolism in the human gut microbiome
Authors: Labarthe Simon , Plancade Sandra , Raguideau Sebastien , Plaza Oñate Florian , Le Chatelier Emmanuelle , Leclerc Marion , Laroche Beatrice 
Published: October 2023

Abstract
Background
With the emergence of metagenomic data, multiple links between the gut microbiome and the host health have been shown. Deciphering these complex interactions require evolved analysis methods focusing on the microbial ecosystem functions. Despite the fact that host or diet-derived fibres are the most abundant nutrients available in the gut, the presence of distinct functional traits regarding fibre and mucin hydrolysis, fermentation and hydrogenotrophic processes has never been investigated.

Results
After manually selecting 91 KEGG orthologies and 33 glycoside hydrolases further aggregated in 101 functional descriptors representative of fibre and mucin degradation pathways in the gut microbiome, we used nonnegative matrix factorization to mine metagenomic datasets. Four distinct metabolic profiles were further identified on a training set of 1153 samples, thoroughly validated on a large database of 2571 unseen samples from 5 external metagenomic cohorts and confirmed with metatranscriptomic data. Profiles 1 and 2 are the main contributors to the fibre-degradation-related metagenome: they present contrasted involvement in fibre degradation and sugar metabolism and are differentially linked to dysbiosis, metabolic disease and inflammation. Profile 1 takes over Profile 2 in healthy samples, and unbalance of these profiles characterize dysbiotic samples. Furthermore, high fibre diet favours a healthy balance between profiles 1 and profile 2. Profile 3 takes over profile 2 during Crohn’s disease, inducing functional reorientations towards unusual metabolism such as fucose and H2S degradation or propionate, acetone and butanediol production. Profile 4 gathers under-represented functions, like methanogenesis. Two taxonomic makes up of the profiles were investigated, using either the covariation of 203 prevalent genomes or metagenomic species, both providing consistent results in line with their functional characteristics. This taxonomic characterization showed that profiles 1 and 2 were respectively mainly composed of bacteria from the phyla Bacteroidetes and Firmicutes while profile 3 is representative of Proteobacteria and profile 4 of methanogens.

Conclusions
Integrating anaerobic microbiology knowledge with statistical learning can narrow down the metagenomic analysis to investigate functional profiles. Applying this approach to fibre degradation in the gut ended with 4 distinct functional profiles that can be easily monitored as markers of diet, dysbiosis, inflammation and disease.
Structural equation modeling of university students’ academic resilience academic well-being, personality and educational attainment in online classes with Tencent Meeting application in China: investigating the role of student engagement
Authors: Sun Yun , Liu Long 
Published: October 2023

Abstract
Background
Online learning presents unique challenges for students, such as reduced social support and increased distractions. Understanding the psychological factors that contribute to educational attainment in online classes is therefore important.

Purpose
This study aimed to investigate the structural relations among the psychological factors: academic resilience, personality, academic well-being, and educational attainment in online classes using the Tencent Meeting application in China. The study also explored the mediating role of student engagement in the relationship between the variables.

Methodology
This study used structural equation modeling (SEM) to investigate the relationships among the variables of the study. The participants were 384 undergraduate, graduate, and postgraduate students from Henan Polytechnic University in China. The participants completed self-report surveys of academic resilience, academic well-being, educational attainment, student engagement and personality types.

Data analysis
The data were analyzed using structural equation modeling (SEM) to examine the relationships among variables. The goodness of fit of the SEM was assessed using several fit indices, including the chi-square test, the comparative fit index (CFI), the Tucker-Lewis index (TLI), and the root mean square error of approximation (RMSEA). The study also conducted mediation analyses to explore the potential mediating roles of learner enjoyment in the relationships between psychological factors and educational attainment.

Findings
The results of the study showed that all variables of the study were positively related to educational attainment. The findings suggest that promoting academic resilience, academic well-being, and student engagement may be effective strategies for enhancing educational attainment in online classes using the Tencent Meeting application in China.

Conclusions
Using the Tencent Meeting application in China, this study provides insights into the complex interplay among several psychological factors and educational attainment in online classes. The findings highlight the importance of promoting academic resilience, personality, academic well-being, and student engagement to enhance educational attainment.
Instructional practices and students’ reading performance: a comparative study of 10 top performing regions in PISA 2018
Authors: Ho Soi Kei , Gan Zhengdong 
Published: October 2023

AbstractThis comparative study investigated the associations between instructional practices and students’ reading performance among 10 top performing regions that participated in the Program for International Student Assessment (PISA) 2018. A nationally representative sample consisting of 80,016 15-year-old students from 5 Asian regions (B-S-J-Z [China], Singapore, Macao, Hong Kong, and Korea) and 5 Western regions (Estonia, Canada, Finland, Ireland, and Poland) were included. A secondary analysis of PISA survey and assessment data was conducted. T test and ANOVA analyses revealed systematic differences in instructional practices of the 10 regions. B-S-J-Z (China) had significantly higher levels of teacher support, teacher-directed instruction, and teacher stimulation than the other sample regions. Asian regions tended to have higher levels of teacher support, teacher-directed instruction, teacher feedback, adaptive instruction, and teacher enthusiasm compared with Western regions, although variations were also found within Asian regions or within Western regions. Hierarchical linear regression (HLR) analyses indicated that reading performance was positively predicted by teacher support, adaptive instruction, teacher stimulation, and teacher enthusiasm, but negatively predicted by teacher-directed instruction and teacher feedback. This study sheds light on the effective instructional practices for optimizing students’ reading performance across different cultural contexts.
Assessing asthma symptoms in children: qualitative research supporting the development of the Pediatric Asthma Diary—Child (PAD-C) and Pediatric Asthma Diary—Observer (PAD-O)
Authors: Bradley Helena , Trennery Claire , Jones Amy M. , Lydon Aoife , White Frances , Williams-Hall Rebecca , Arbuckle Rob , Tomaszewski Erin , Shih Vivian H. , Haughney John , Eisen Amanda , Winders Tonya , Coons Stephen Joel , Eremenco Sonya ,   the Patient-Reported Outcome Consortium’s Pediatric Asthma Working Group, Nelsen Linda , Tabberer Maggie , Mattera Maria , Lehane Asha , Morgan Lucy , Krishnan Jerry 
Published: October 2023

Abstract
Background
Pediatric asthma has been identified by regulators, clinicians, clinical trial sponsors, and caregivers as an area in need of novel fit-for-purpose clinical outcome assessments (COAs) developed in accordance with the U.S. Food and Drug Administration’s (FDA’s) regulatory guidance for evaluating clinical benefit in treatment trials. To address this gap, the Patient-Reported Outcome (PRO) Consortium’s Pediatric Asthma Working Group has continued development of 2 COAs to assess asthma signs and symptoms in pediatric asthma clinical trials to support efficacy endpoints: a PRO measure, the Pediatric Asthma Diary—Child (PAD-C) for children 8–11 years old (y.o.) and an observer-reported outcome measure, the Pediatric Asthma Diary-Observer (PAD—O) for caregivers of children 4–11 y.o. This qualitative research aimed to generate evidence regarding the content validity of the PAD-C and PAD-O.

Methods
Semi-structured combined concept elicitation and cognitive interviews were conducted with a diverse sample of U.S. participants (15 children 8–11 y.o. and 30 caregivers of children 4–11 y.o.). All children had clinician-diagnosed mild to severe asthma. Interviews explored the experience of pediatric asthma and assessed the understanding and relevance of both measures. Interviews were conducted across 3 iterative rounds to allow for modifications.

Results
Concept elicitation findings demonstrated that the core sign/symptom and impact concepts assessed in the PAD-C (cough, hard to breathe, out of breath, wheezing, chest tightness, and nighttime awakenings/symptoms) and PAD-O (cough, difficulty breathing, short of breath, wheezing, and nighttime awakenings/signs) correspond to those most frequently reported by participants; concept saturation was achieved. All PAD-C and PAD-O instructions and core items were well understood and considered relevant by most participants. Feedback from participants, the Pediatric Asthma Working Group, advisory panel, and FDA supported modifications to the measures, including addition of 1 new item to both measures and removal of 1 caregiver item.

Conclusions
Findings provide strong support for the content validity of both measures. The cross-sectional measurement properties of both measures and their user experience and feasibility in electronic format will be assessed in a future quantitative pilot study with qualitative exit interviews, intended to support the reliability, construct validity, final content, and, ultimately, FDA qualification of the measures.
Ceftiofur treatment of sows results in long-term alterations in the nasal microbiota of the offspring that can be ameliorated by inoculation of nasal colonizers
Authors: Blanco-Fuertes Miguel , Sibila Marina , Franzo Giovanni , Obregon-Gutierrez Pau , Illas Francesc , Correa-Fiz Florencia , Aragón Virginia 
Published: October 2023

Abstract
Background
The nasal microbiota of the piglet is a reservoir for opportunistic pathogens that can cause polyserositis, such as Glaesserella parasuis, Mycoplasma hyorhinis or Streptococcus suis. Antibiotic treatment is a strategy to control these diseases, but it has a detrimental effect on the microbiota. We followed the piglets of 60 sows from birth to 8 weeks of age, to study the effect of ceftiofur on the nasal microbiota and the colonization by pathogens when the treatment was administered to sows or their litters. We also aimed to revert the effect of the antibiotic on the nasal microbiota by the inoculation at birth of nasal colonizers selected from healthy piglets. Nasal swabs were collected at birth, and at 7, 15, 21 and 49 days of age, and were used for pathogen detection by PCR and bacterial culture, 16S rRNA amplicon sequencing and whole shotgun metagenomics. Weights, clinical signs and production parameters were also recorded during the study.

Results
The composition of the nasal microbiota of piglets changed over time, with a clear increment of Clostridiales at the end of nursery. The administration of ceftiofur induced an unexpected temporary increase in alpha diversity at day 7 mainly due to colonization by environmental taxa. Ceftiofur had a longer impact on the nasal microbiota of piglets when administered to their sows before farrowing than directly to them. This effect was partially reverted by the inoculation of nasal colonizers to newborn piglets and was accompanied by a reduction in the number of animals showing clinical signs (mainly lameness). Both interventions altered the colonization pattern of different strains of the above pathogens. In addition, the prevalence of resistance genes increased over time in all the groups but was significantly higher at weaning when the antibiotic was administered to the sows. Also, ceftiofur treatment induced the selection of more beta-lactams resistance genes when it was administered directly to the piglets.

Conclusions
This study shed light on the effect of the ceftiofur treatment on the piglet nasal microbiota over time and demonstrated for the first time the possibility of modifying the piglets’ nasal microbiota by inoculating natural colonizers of the upper respiratory tract.