bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of Personality Disorder Symptoms on Treatment Outcomes in Bipolar Disorder: A Secondary Analysis of a Randomised Controlled Trial: L’influence des symptômes du trouble de la personnalité sur les résultats du traitement dans le trouble bipolaire : Une analyse secondaire d’un essai randomisé contrôlé
Authors: Sarmiento Alessandra , Dean Olivia M. , Kavanagh Bianca E. , Mohebbi Mohammadreza , Berk Michael , Dodd Seetal , Cotton Sue M. , Malhi Gin S. , Ng Chee H. , Turner Alyna 
Published: November 2023

Objectives Many people who are diagnosed with bipolar disorder also have comorbid personality disorder. Few studies have explored how personality disorder may influence pharmacological treatment outcomes. The aim of this study was to conduct a secondary analysis of data from a clinical trial of adjunctive nutraceutical treatments for bipolar depression, to determine whether maladaptive personality traits influence treatment outcomes. Methods Scores on the Standardised Assessment of Personality – Abbreviated Scale screener were used to classify participants as having bipolar disorder with ( n = 119) and without ( n = 29) above threshold personality disorder symptoms (personality disorder). Outcome measures included: The Montgomery Åsberg Depression Rating Scale, Clinical Global Impressions and Improvement Severity Scales, Patient Global Impressions–Improvement scale, Bipolar Depression Rating Scale, Range of Impaired Functioning Tool, Social and Occupational Functioning Assessment Scale and Quality of Life and Enjoyment Scale (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form). Generalised estimated equations examined the two-way interactions of personality disorder by time or treatment and investigated personality disorder as a non-specified predictor of outcomes. Results Over time, the Patient Global Impressions–Improvement scores were significantly higher in those in the personality disorder group. No other significant differences in the two-way interactions of personality disorder by treatment group or personality disorder by time were found. Personality disorder was a significant but non-specific predictor of poorer outcomes on the Bipolar Depression Rating Scale, Range of Impaired Functioning Tool, and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, regardless of time or treatment group. Conclusions This study highlights the potential impact of maladaptive personality traits on treatment outcomes and suggests that the presence of comorbid personality disorder may confer additional burden and compromise treatment outcomes. This warrants further investigation as does the corroboration of these exploratory findings. This is important because understanding the impact of comorbid personality disorder on bipolar disorder may enable the development of effective psychological and pharmacotherapeutic options for personalised treatments.
Pharmacological profiling of a berbamine derivative for lymphoma treatment
Authors: Xu Senlin , Wu Shunquan , Zhang Mingfeng , Xie Jun , Lin Min , Jin Lihua , Zhang Jiawei , Wang Yangmeng , Fan Mingjie , Fang Zhipeng , Li Weini , Ouyang Ching , Kwon David , Que Natalie , Li Zhirou , Mao Jinge , Chen Haonan , Harris Josephine , Wu Xiwei , Wu Jun , Yin Hongwei , Chan Wing C. , Horne David , Huang Wendong 
Published: November 2023

Abstract
Ca2+/calmodulin-dependent protein kinase II γ (CAMKIIγ) has been identified as a potential target for treating cancer. Based on our previous study of berbamine (BBM) as a CAMKIIγ inhibitor, we have synthesized a new BBM derivative termed PA4. Compared with BBM, PA4 showed improved potency and specificity and was more cytotoxic against lymphoma and leukemia than against other types of cancer. In addition to indirectly targeting c-Myc protein stability, we demonstrated that its cytotoxic effects were also mediated via increased reactive oxygen species production in lymphoma cells. PA4 significantly impeded tumor growth in vivo in a xenograft T-cell lymphoma mouse model. Pharmacokinetics studies demonstrated quick absorption into plasma after oral administration, with a maximum concentration of 1680 ± 479 ng/mL at 5.33 ± 2.31 hours. The calculated oral absolute bioavailability was 34.1%. Toxicity assessment of PA4 showed that the therapeutic window used in our experiments was safe for future development. Given its efficacy, safety, and favorable pharmacokinetic profile, PA4 is a potential lead candidate for treating lymphoma.
Deep learning predicts therapy-relevant genetics in acute myeloid leukemia from Pappenheim-stained bone marrow smears
Authors: Kockwelp Jacqueline , Thiele Sebastian , Bartsch Jannis , Haalck Lars , Gromoll Jörg , Schlatt Stefan , Exeler Rita , Bleckmann Annalen , Lenz Georg , Wolf Sebastian , Steffen Björn , Berdel Wolfgang E. , Schliemann Christoph , Risse Benjamin , Angenendt Linus 
Published: November 2023

Abstract
The detection of genetic aberrations is crucial for early therapy decisions in acute myeloid leukemia (AML) and recommended for all patients. Because genetic testing is expensive and time consuming, a need remains for cost-effective, fast, and broadly accessible tests to predict these aberrations in this aggressive malignancy. Here, we developed a novel fully automated end-to-end deep learning pipeline to predict genetic aberrations directly from single-cell images from scans of conventionally stained bone marrow smears already on the day of diagnosis. We used this pipeline to compile a multiterabyte data set of &gt;2 000 000 single-cell images from diagnostic samples of 408 patients with AML. These images were then used to train convolutional neural networks for the prediction of various therapy-relevant genetic alterations. Moreover, we created a temporal test cohort data set of &gt;444 000 single-cell images from further 71 patients with AML. We show that the models from our pipeline can significantly predict these subgroups with high areas under the curve of the receiver operating characteristic. Potential genotype-phenotype links were visualized with 2 different strategies. Our pipeline holds the potential to be used as a fast and inexpensive automated tool to screen patients with AML for therapy-relevant genetic aberrations directly from routine, conventionally stained bone marrow smears already on the day of diagnosis. It also creates a foundation to develop similar approaches for other bone marrow disorders in the future.
Comparison of in-gel and in-solution proteolysis in the proteome profiling of organ perfusion solutions
Authors: Snashall Corinna M. , Sutton Chris W. , Faro Letizia Lo , Ceresa Carlo , Ploeg Rutger , Shaheed Sadr ul 
Published: November 2023

Abstract
Purpose
The organ perfusion solution (perfusate), collected at clinically and temporally significant stages of the organ preservation and transplantation process, provides a valuable insight into the biological status of an organ over time and prior to reperfusion (transplantation) in the recipient. The objective of this study was to assess two bottom-up proteomics workflows for the extraction of tryptic peptides from the perfusate.

Experimental design
Two different kinds of perfusate samples from kidney and liver trials were profiled using liquid chromatography–mass spectrometry (LC-MS/MS). The preparation of clean peptide mixtures for downstream analysis was performed considering different aspects of sample preparation; protein estimation, enrichment, in-gel and urea-based in-solution digestion.

Results
In-solution digestion of perfusate allowed identification of the highest number of peptides and proteins with greater sequence coverage and higher confidence data in kidney and liver perfusate. Key pathways identified by gene ontology analysis included complement, coagulation and antioxidant pathways, and a number of biomarkers previously linked to ischemia-reperfusion injury were also observed in perfusate.

Conclusions
This study showed that in-solution digestion is a more efficient method for LC-MS/MS analysis of kidney and liver organ perfusion solutions. This method is also quicker and easier than in-gel digestion, allowing for greater sample throughput, with fewer opportunities for experimental error or peptide loss.
The incidence of chronic diarrhea decreases with increasing serum calcium levels: a cross-sectional study based on NHANES 2005–2010
Authors: Li Xiaotong , Li Jiali , Cao Zhiqun , Kang Nan 
Published: November 2023

Abstract
Background
Chronic diarrhea is difficult to prevent and treat due to its complex etiology and pathogenesis. It places a huge burden on patients and public healthcare. It is known that the regulation of body homeostasis relies heavily on calcium. However, in the general population, the relationship between calcium and chronic diarrhea remains uncertain.

Methods
We assessed the association between serum calcium and diarrhea using data from the 2005–2010 National Health and Nutrition Examination Survey (NHANES). Serum calcium level was measured from collected blood samples. Diarrhea was assessed using the Bristol Stool Scale (BSFS) (types 1–7). The stability of the results was assessed using logistic regression and sensitivity analysis. The dose–response association between serum calcium and the risk of diarrhea was analyzed using a restricted cubic spline plot.

Results
This study included 12,342 participants. In each of the five models, an increased calcium level was negatively associated with the incidence of diarrhea (OR[95%CI]:0.26 [0.13–0.53], 0.28 [0.14–0.58], 0.4 [0.19–0.82], 0.27 [0.11–0.64] and 0.24 [0.10–0.59], respectively). When serum calcium was analyzed as a categorical variable, a significant association between serum calcium and diarrhea prevalence was found. The restricted cubic spline plot showed a linear relationship between serum calcium and diarrhea. Sensitivity analysis confirmed that the results were stable.

Conclusion
The results of our cross-sectional study suggest that a higher level of serum calcium may reduce the incidence of diarrhea. In the future, this finding should be further validated in a randomized controlled trial.
Different lumbar fusion techniques for lumbar spinal stenosis: a Bayesian network meta-analysis
Authors: Li Wei , Wei Haibin , Zhang Ran 
Published: November 2023

Abstract
Objective
To comprehensively compare and assess the effects of different lumbar fusion techniques in patients with lumbar spinal stenosis (LSS).

Methods
PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched up to December 24, 2022 in this network meta-analysis. Outcomes were pain (pain, low back pain, and leg pain), Japanese Orthopaedic Association (JOA), Oswestry Disability Index (ODI), complications, reoperation, and fusion. Network plots illustrated the direct and indirect comparisons of different fusion techniques for the outcomes. League tables showed the comparisons of any two fusion techniques, based on both direct and indirect evidence. The efficacy of each fusion technique for LSS was ranked by rank probabilities.

Results
Totally 29 studies involving 2,379 patients were eligible. For pain, percutaneous endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) was most likely to be the best technique, followed by minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF), extreme lateral interbody fusion (XLIF), and transforaminal lumbar interbody fusion (TLIF). Percutaneous endoscopic posterior lumbar interbody fusion (Endo-PLIF) had the greatest likelihood to be the optimal technique for low back pain, followed sequentially by MIS-TLIF, minimally invasive posterior lumbar interbody fusion (MIS-PLIF), XLIF, Endo-TLIF, TLIF, oblique lumbar interbody fusion (OLIF), posterior lumbar interbody fusion (PLIF), and posterolateral lumbar fusion (PLF). MIS-PLIF was ranked the most effective technique concerning leg pain, followed by Endo-TLIF, MIS-TLIF, TLIF, Endo-PLIF, PLIF, OLIF, PLF, and XLIF. As regards JOA scores, Endo-TLIF had the maximum probability to be the best technique, followed by MIS-TLIF and TLIF. Endo-PLIF had the greatest likelihood to be the optimum technique for complications, followed by TLIF, MIS-TLIF, Endo-TLIF, OLIF, and XLIF.

Conclusion
Minimally invasive fusion techniques may be effective in the treatment of LSS, compared with traditional techniques. Minimally invasive techniques were likely non-inferior with regards to postoperative complications.
Selection of M7G-related lncRNAs in kidney renal clear cell carcinoma and their putative diagnostic and prognostic role
Authors: Zhong Shuangze , Chen Shangjin , Lin Hansheng , Luo Yuancheng , He Jingwei 
Published: November 2023

Abstract
Background
Kidney renal clear cell carcinoma (KIRC) is a common malignant tumor of the urinary system. This study aims to develop new biomarkers for KIRC and explore the impact of biomarkers on the immunotherapeutic efficacy for KIRC, providing a theoretical basis for the treatment of KIRC patients.

Methods
Transcriptome data for KIRC was obtained from the The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Weighted gene co-expression network analysis identified KIRC-related modules of long noncoding RNAs (lncRNAs). Intersection analysis was performed differentially expressed lncRNAs between KIRC and normal control samples, and lncRNAs associated with N(7)-methylguanosine (m7G), resulting in differentially expressed m7G-associated lncRNAs in KIRC patients (DE-m7G-lncRNAs). Machine Learning was employed to select biomarkers for KIRC. The prognostic value of biomarkers and clinical features was evaluated using Kaplan-Meier (K-M) survival analysis, univariate and multivariate Cox regression analysis. A nomogram was constructed based on biomarkers and clinical features, and its efficacy was evaluated using calibration curves and decision curves. Functional enrichment analysis was performed to investigate the functional enrichment of biomarkers. Correlation analysis was conducted to explore the relationship between biomarkers and immune cell infiltration levels and common immune checkpoint in KIRC samples.

Results
By intersecting 575 KIRC-related module lncRNAs, 1773 differentially expressed lncRNAs, and 62 m7G-related lncRNAs, we identified 42 DE-m7G-lncRNAs. Using XGBoost and Boruta algorithms, 8 biomarkers for KIRC were selected. Kaplan-Meier survival analysis showed significant survival differences in KIRC patients with high and low expression of the PTCSC3 and RP11-321G12.1. Univariate and multivariate Cox regression analyses showed that AP000696.2, PTCSC3 and clinical characteristics were independent prognostic factors for patients with KIRC. A nomogram based on these prognostic factors accurately predicted the prognosis of KIRC patients. The biomarkers showed associations with clinical features of KIRC patients, mainly localized in the cytoplasm and related to cytokine-mediated immune response. Furthermore, immune feature analysis demonstrated a significant decrease in immune cell infiltration levels in KIRC samples compared to normal samples, with a negative correlation observed between the biomarkers and most differentially infiltrating immune cells and common immune checkpoints.

Conclusion
In summary, this study discovered eight prognostic biomarkers associated with KIRC patients. These biomarkers showed significant correlations with clinical features, immune cell infiltration, and immune checkpoint expression in KIRC patients, laying a theoretical foundation for the diagnosis and treatment of KIRC.
The validity of Engagement and Feedback Assessments (EFAs): identifying students at risk of failing
Authors: Kemp Paul R. , Bradshaw Jacob M. , Pandya Brijmohan , Davies Daniel , Morrell Mary J. , Sam Amir H. 
Published: November 2023

Abstract
Background
Imperial College School of Medicine, London UK, introduced a new curriculum in 2019, with a focus on the GMC outcomes for graduates, and pedagogy best practice. The new curriculum included formative assessments, named engagement and feedback assessments (EFAs), to support learning, and attainment in the summative examinations. The aims of this study were to assess the validity of EFAs and to determine whether they have utility as a modified form of programmatic assessment to inform decision-making regarding possible interventions by measuring and analysing attendance at and performance in these formative events.

Methods
Seven hundred and sixty-one students were included in the study and assessment results were included for academic years 2019/20 to 2020/21. Forty-one data points per student, (27 in Year 1 and 14 in Year 2) were used, to compare EFA scores with the summative performance. Attendance was monitored through engagement with the EFAs.

Results
Cohort 1 (enrolled 2019): In year 1, EFAs were associated with summative exam scores (overall r = 0.63, p < 0.001). Year 2, EFA scores were also associated with summative scores (overall r = 0.57, p < 0.001), including the clinical practical assessment (r = 0.45, p < 0.001).
Missing two or more EFAs was associated with a significant increase in the likelihood of failing one or more summative examinations in the first year (OR: 7.97, 95% CI 2.65–34.39) and second year (OR: 3.20, 95% CI 1.74–5.95). Missing more than two EFAs in their first year was also associated with a higher risk of failing a summative examination in the second year (OR: 2.47, 95% CI 1.33–4.71). Students who increased their attendance between year 1 and 2 fared better in summative assessment than those who maintained poor attendance, whereas those that reduced their attendance fared worse than those that maintained high attendance.
Cohort 2 (enrolled 2020): Analysis of cohort 2 supported these findings and in this cohort missing two or more EFAs was again associated with an increased likelihood of failing a summative examination (OR = 4.00, 95% CI = 2.02–7.90).

Conclusion
Our EFA model has validity in predicting performance in summative assessments and can inform prospective interventions to support students’ learning. Enhancing attendance and engagement can improve outcomes.
Proto-oncogene mutations in middle ear cholesteatoma contribute to its pathogenesis
Authors: Satoh Chisei , Yoshiura Koh-ichiro , Mishima Hiroyuki , Yoshida Haruo , Takahashi Haruo , Kumai Yoshihiko 
Published: November 2023

Abstract
Background
Chronic inflammation causes bone destruction in middle ear cholesteatomas (MECs). However, the causes of their neoplastic features remain unknown. The present study demonstrated for the first time that neoplastic features of MEC are based on proto-oncogene mutations.

Results
DNA was extracted from MEC and blood samples of five patients to detect somatic mutations using depth-depth exome sequencing. Exons with somatic variants were analyzed using an additional 17 MEC/blood test pairs. Variants detected in MECs but not in blood were considered pathogenic variant candidates. We analyzed the correlation between proto-oncogene (NOTCH1 and MYC) variants and the presence of bone destruction and granulation tissue formation. MYC and NOTCH1 variants were detected in two and five of the 22 samples, respectively. Two of the NOTCH1 variants were located in its specific functional domain, one was truncating and the other was a splice donor site variant. Mutations of the two genes in attic cholesteatomas (n = 14) were significantly related with bone destruction (p = 0.0148) but not with granulation tissue formation (p = 0.399).

Conclusions
This is the first study to demonstrate a relationship between neoplastic features of MEC and proto-oncogene mutations.
Identification and validation of autophagy-related genes in primary open-angle glaucoma
Authors: Xu Wanjing , Sun Yuhao , Zhao Shuang , Zhao Jun , Zhang Juanmei 
Published: November 2023

Abstract
Background
As the most common type of glaucoma, the etiology of primary open-angle glaucoma (POAG) has not been unified. Autophagy may affect the occurrence and development of POAG, while the specific mechanism and target need to be further explored.

Methods
The GSE27276 dataset from the Gene Expression Omnibus (GEO) database and the autophagy gene set from the GeneCards database were selected to screen differentially expressed autophagy-related genes (DEARGs) of POAG. Hub DEARGs were selected by constructing protein-protein interaction (PPI) networks and utilizing GSE138125 dataset. Subsequently, immune cell infiltration analysis, genome-wide association study (GWAS) analysis, gene set enrichment analysis (GSEA) and other analyses were performed on the hub genes. Eventually, animal experiments were performed to verify the mRNA levels of the hub genes by quantitative real time polymerase chain reaction (qRT-PCR).

Results
A total of 67 DEARGs and 2 hub DEARGs, HSPA8 and RPL15, were selected. The hub genes were closely related to the level of immune cell infiltration. GWAS analysis confirmed that the causative regions of the 2 hub genes in glaucoma were on chromosome 11 and chromosome 3, respectively. GSEA illustrated that pathways enriched for highly expressed HSPA8 and RPL15 contained immunity, autophagy, gene expression and energy metabolism-related pathways. qRT-PCR confirmed that the expression of Hspa8 and Rpl15 in the rat POAG model was consistent with the results of bioinformatics analysis.

Conclusions
This study indicated that HSPA8 and RPL15 may affect the progression of POAG by regulating autophagy and provided new ideas for the pathogenesis and treatment of POAG.
Development and psychometric evaluation of item banks for memory and attention – supplements to the EORTC CAT Core instrument
Authors: Rogge AA , Petersen MA , Aaronson NK , Conroy T , Dirven L , Fischer F , Habets EJJ , Reijneveld JC , Rose M , Sleurs C , Taphoorn M , Tomaszewski KA , Vachon H , Young T , Groenvold M ,   on behalf of the EORTC Quality of Life Group
Published: November 2023

Abstract
Background
Cancer patients may experience a decrease in cognitive functioning before, during and after cancer treatment. So far, the Quality of Life Group of the European Organisation for Research and Treatment of Cancer (EORTC QLG) developed an item bank to assess self-reported memory and attention within a single, cognitive functioning scale (CF) using computerized adaptive testing (EORTC CAT Core CF item bank). However, the distinction between different cognitive functions might be important to assess the patients’ functional status appropriately and to determine treatment impact. To allow for such assessment, the aim of this study was to develop and psychometrically evaluate separate item banks for memory and attention based on the EORTC CAT Core CF item bank.

Methods
In a multistep process including an expert-based content analysis, we assigned 44 items from the EORTC CAT Core CF item bank to the memory or attention domain. Then, we conducted psychometric analyses based on a sample used within the development of the EORTC CAT Core CF item bank. The sample consisted of 1030 cancer patients from Denmark, France, Poland, and the United Kingdom. We evaluated measurement properties of the newly developed item banks using confirmatory factor analysis (CFA) and item response theory model calibration.

Results
Item assignment resulted in 31 memory and 13 attention items. Conducted CFAs suggested good fit to a 1-factor model for each domain and no violations of monotonicity or indications of differential item functioning. Evaluation of CATs for both memory and attention confirmed well-functioning item banks with increased power/reduced sample size requirements (for CATs ≥ 4 items and up to 40% reduction in sample size requirements in comparison to non-CAT format).

Conclusion
Two well-functioning and psychometrically robust item banks for memory and attention were formed from the existing EORTC CAT Core CF item bank. These findings could support further research on self-reported cognitive functioning in cancer patients in clinical trials as well as for real-word-evidence. A more precise assessment of attention and memory deficits in cancer patients will strengthen the evidence on the effects of cancer treatment for different cancer entities, and therefore contribute to shared and informed clinical decision-making.