bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐Term POTS Outcomes Survey: Diagnosis, Therapy, and Clinical Outcomes
Authors: Boris Jeffrey R. , Shadiack Edward C. , McCormick Elizabeth M. , MacMullen Laura , George‐Sankoh Ibrahim , Falk Marni J. 
Published: July 2024

Background
Limited data exist on long‐term outcomes in individuals with postural orthostatic tachycardia syndrome (POTS). We designed an electronic questionnaire assessing various aspects of outcomes among patients diagnosed and treated in a single‐center pediatric POTS clinical program.

Methods and Results
The LT‐POTS (Long Term POTS Outcomes Survey) included questions about quality of life, symptoms, therapies, education, employment, and social impact of disease. Patients age≤18 years at POTS diagnosis who were managed in the Children's Hospital of Philadelphia POTS Program were included. A total of 227 patients with POTS responded with sufficient data for interpretation. The mean age of respondents was 21.8±3.5 years. The median age of symptom onset was 13 (interquartile range 11–14) years, with mean 9.6±3.4 years symptom duration. Multiple cardiovascular, neurologic, and gastrointestinal symptoms were reported. Symptom prevalence and severity were worse for female patients, with 99% of patients reporting ongoing symptoms. Quality of life showed moderate function and limitation, with more severe limitations in energy/fatigue and general health. Nearly three quarters of patients had diagnostic delays, and over half were told that their symptoms were “in their head.” Multiple medications were used and were felt to be effective, whereas fewer nonpharmacologic interventions demonstrated efficacy. Nearly 90% of patients required continued nonpharmacologic therapy to control symptoms.

Conclusions
POTS is a chronic disorder leading to significant disability with a range of multisystem problems. Although symptoms can be modifiable, it rarely spontaneously resolves. Improved understanding of POTS presentation and therapeutic approaches may inform provider education, improve diagnostic success, and help patients self‐advocate for appropriate medical management approaches.
Developmental change of brain volume in Rett syndrome in Taiwan
Authors: Jan Tz-Yun , Wong Lee-Chin , Hsu Chia-Jui , Huang Chien-Feng Judith , Peng Steven Shinn-Forng , Tseng Wen-Yih Isaac , Lee Wang-Tso 
Published: July 2024

Abstract
Objective
Rett syndrome (RTT) is characterized by neurological regression. This pioneering study investigated the effect of age on brain volume reduction by analyzing magnetic resonance imaging findings in participants with RTT, ranging from toddlers to adults.

Methods
Functional evaluation and neuroimaging were performed. All scans were acquired using a Siemens Tim Trio 3 T scanner with a 32-channel head coil.

Results
The total intracranial volume and cerebral white matter volume significantly increased with age in the control group compared with that in the RTT group (p < 0.05). Cortical gray matter volume reduction in the RTT group continued to increase in bilateral parietal lobes and left occipital lobes (p < 0.05). The differences in cortical gray matter volume between typically developing brain and RTT-affected brain may tend to continuously increase until adulthood in both temporal lobes although not significant after correction for multiple comparison.

Conclusions
A significant reduction in brain volume was observed in the RTT group. Cortical gray matter volume in the RTT group continued to reduce in bilateral parietal lobes and left occipital lobes. These results provide a baseline for future studies on the effect of RTT treatment and related neuroscience research.
Genome-wide identification and molecular evolution of Dof transcription factors in Cyperus esculentus
Authors: Fu Chun , Liao ZiHui , Jiang Na , Yang YaoJun 
Published: July 2024

AbstractDof transcription factor family in Cyperus esculentus genome was identified and analyzed using bioinformatics. The analysis results revealed that C.esculentus genome contains 29 Dof genes (CesDof), all of which are located in the nucleus according to subcellular localization prediction. CesDof proteinrs have a range of 124 to 512 amino acids, with most being basic proteins. Their secondary structure was mainly irregular curl. The promoter sequence of CesDof genes contains cis-acting elements that respond to light, drought, hormones, low temperature, and circadian rhythm. Codon preference analysis showed that CesDof genes' codon preference ends in T/A. Collinearity analysis revealed that C.esculentus had three pairs of collinear CesDof genes. Additionally, there were 15 pairs of collinear genes between C.esculentus and Arabidopsis thaliana. The genetic relationship between C.esculentus and Rhynchospora pubera was found to be the closest. Phylogenetic tree analysis revealed that 29 CesDof genes of C.esculentus can be classified into 4 subgroups. Additionally, 144 miRNAs were predicted to target these CesDof genes. Furthermore, protein interaction analysis indicated that 15 Dof proteins in C.esculentus had interactions. The qRT-PCR verification results of drought stress and salt stress treatment experiments showed that most CesDof genes were involved in drought stress and salt stress responses, and the gene expression trends under drought stress and salt stress conditions were consistent. These results lay a theoretical foundation for further studying the molecular functions of Dof gene family in C.esculentus and its molecular mechanisms in regulating the life activities of C.esculentus.
Systematic characterization of immunoglobulin loci and deep sequencing of the expressed repertoire in the Atlantic cod (Gadus morhua)
Authors: Györkei Ádám , Johansen Finn-Eirik , Qiao Shuo-Wang 
Published: July 2024

Abstract
Background
The Atlantic cod is a prolific species in the Atlantic, despite its inconsistent specific antibody response. It presents a peculiar case within vertebrate immunology due to its distinct immune system, characterized by the absence of MHCII antigen presentation pathway, required for T cell-dependent antibody responses. Thorough characterisation of immunoglobulin loci and analysis of the antibody repertoire is necessary to further our understanding of the Atlantic cod’s immune response on a molecular level.

Results
A comprehensive search of the cod genome (gadmor3.0) identified the complete set of IgH genes organized into three sequential translocons on chromosome 2, while IgL genes were located on chromosomes 2 and 5. The Atlantic cod displayed a moderate germline V gene diversity, comprising four V gene families for both IgH and IgL, each with distinct chromosomal locations and organizational structures. 5’RACE sequencing revealed a diverse range of heavy chain CDR3 sequences and relatively limited CDR3 diversity in light chains. The analysis highlighted a differential impact of V-gene germline CDR3 length on receptor CDR3 length between heavy and light chains, underlining different recombination processes.

Conclusions
This study reveals that the Atlantic cod, despite its inconsistent antibody response, maintains a level of immunoglobulin diversity comparable to other fish species. The findings suggest that the extensive recent duplications of kappa light chain genes do not result in increased repertoire diversity. This research provides a comprehensive view of the Atlantic cod's immunoglobulin gene organization and repertoire, necessary for future studies of antibody responses at the molecular level.
A comparison of the TempO-Seq and Affymetrix microarray platform using RTqPCR validation
Authors: Wehr Matthias M. , Reamon-Buettner Stella Marie , Ritter Detlef , Knebel Jan , Niehof Monika , Escher Sylvia E. 
Published: July 2024

AbstractNext-generation risk assessment relies on mechanistic data from new approach methods, including transcriptome data. Various technologies, such as high-throughput targeted sequencing methods and microarray technologies based on hybridization with complementary probes, are used to determine differentially expressed genes (DEGs). The integration of data from different technologies requires a good understanding of the differences arising from the use of various technologies.To better understand the differences between the TempO-Seq platform and Affymetrix chip technology, whole-genome data for the volatile compound dimethylamine were compared. Selected DEGs were also confirmed using RTqPCR validation. Although the overlap of DEGs between TempO-Seq and Affymetrix was no higher than 37%, a comparison of the gene regulation in terms of log2fold changes revealed a very high concordance. RTqPCR confirmed the majority of DEGs from either platform in the examined dataset. Only a few conflicts were found (11%), while 22% were not confirmed, and 3% were not detected.Despite the observed differences between the two platforms, both can be validated using RTqPCR. Here we highlight some of the differences between the two platforms and discuss their applications in toxicology.
Diagnosing and managing prescription opioid use disorder in patients prescribed opioids for chronic pain in Australian general practice settings: a qualitative study using the theory of Planned Behaviour
Authors: Wilson HHK , Roxas B. Harris , Lintzeris N. , Harris MF 
Published: July 2024

Abstract
Background
Chronic pain is a debilitating and common health issue. General Practitioners (GPs) often prescribe opioids to treat chronic pain, despite limited evidence of benefit and increasing evidence of harms, including prescription Opioid Use Disorder (pOUD). Australian GPs are worried about the harms of long-term opioids, but few are involved in the treatment of pOUD. There is little research on GPs’ experiences diagnosing and managing pOUD in their chronic pain patients.

Methods
This qualitative research used semi-structured interviews and a case study to investigate GPs’ experiences through the lens of the Theory of Planned Behaviour (TPB). TPB describes three factors, an individual’s perceived beliefs/attitudes, perceived social norms and perceived behavioural controls. Participants were interviewed via an online video conferencing platform. Interviews were transcribed verbatim and thematically analysed.

Results
Twenty-four GPs took part. Participants were aware of the complex presentations for chronic pain patients and concerned about long-term opioid use. Their approach was holistic, but they had limited understanding of pOUD diagnosis and suggested that pOUD had only one treatment: Opioid Agonist Treatment (OAT). Participants felt uncomfortable prescribing opioids and were fearful of difficult, conflictual conversations with patients about the possibility of pOUD. This led to avoidance and negative attitudes towards diagnosing pOUD. There were few positive social norms, few colleagues diagnosed or managed pOUD. Participants reported that their colleagues only offered positive support as this would allow them to avoid managing pOUD themselves, while patients and other staff were often unsupportive. Negative behavioural controls were common with low levels of knowledge, skill, professional supports, inadequate time and remuneration described by many participants. They felt OAT was not core general practice and required specialist management. This dichotomous approach was reflected in their views that the health system only supported treatment for chronic pain or pOUD, not both conditions.

Conclusions
Negative beliefs, negative social norms and negative behavioural controls decreased individual behavioural intention for this group of GPs. Diagnosing and managing pOUD in chronic pain patients prescribed opioids was perceived as difficult and unsupported. Interventions to change behaviour must address negative perceptions in order to lead to more positive intentions to engage in the management of pOUD.
Integrating lipid metabolite analysis with MRI-based transformer and radiomics for early and late stage prediction of oral squamous cell carcinoma
Authors: Li Wen , Li Yang , Gao Shiyu , Huang Nengwen , Kojima Ikuho , Kusama Taro , Ou Yanjing , Iikubo Masahiro , Niu Xuegang 
Published: July 2024

Abstract
Background
Oral Squamous Cell Carcinoma (OSCC) presents significant diagnostic challenges in its early and late stages. This study aims to utilize preoperative MRI and biochemical indicators of OSCC patients to predict the stage of tumors.

Methods
This study involved 198 patients from two medical centers. A detailed analysis of contrast-enhanced T1-weighted (ceT1W) and T2-weighted (T2W) MRI were conducted, integrating these with biochemical indicators for a comprehensive evaluation. Initially, 42 clinical biochemical indicators were selected for consideration. Through univariate analysis and multivariate analysis, only those indicators with p-values less than 0.05 were retained for model development. To extract imaging features, machine learning algorithms in conjunction with Vision Transformer (ViT) techniques were utilized. These features were integrated with biochemical indicators for predictive modeling. The performance of model was evaluated using the Receiver Operating Characteristic (ROC) curve.

Results
After rigorously screening biochemical indicators, four key markers were selected for the model: cholesterol, triglyceride, very low-density lipoprotein cholesterol and chloride. The model, developed using radiomics and deep learning for feature extraction from ceT1W and T2W images, showed a lower Area Under the Curve (AUC) of 0.85 in the validation cohort when using these imaging modalities alone. However, integrating these biochemical indicators improved the model’s performance, increasing the validation cohort AUC to 0.87.

Conclusion
In this study, the performance of the model significantly improved following multimodal fusion, outperforming the single-modality approach.

Clinical relevance statement
This integration of radiomics, ViT models, and lipid metabolite analysis, presents a promising non-invasive technique for predicting the staging of OSCC.
KLK7 expression in human tumors: a tissue microarray study on 13,447 tumors
Authors: Kind Simon , Castillo Carolina Palacios , Schlichter Ria , Gorbokon Natalia , Lennartz Maximilian , Hornsteiner Lisa S. , Dwertmann Rico Sebastian , Reiswich Viktor , Viehweger Florian , Kluth Martina , Hube-Magg Claudia , Bernreuther Christian , Büscheck Franziska , Clauditz Till S. , Fraune Christoph , Hinsch Andrea , Krech Till , Lebok Patrick , Steurer Stefan , Burandt Eike , Minner Sarah , Marx Andreas H. , Simon Ronald , Wilczak Waldemar , Sauter Guido , Menz Anne , Jacobsen Frank 
Published: July 2024

Abstract
Background
Kallikrein-related peptidase 7 (KLK7) is a chymotrypsin-like serine protease which is essential for the desquamation of corneocytes and thus plays a pivotal role in maintaining skin homeostasis. In cancer, KLK7 overexpression was suggested to represent a route for metastasis through cleavage of cell junction and extracellular matrix proteins of cancer cells.

Methods
To comprehensively determine KLK7 protein expression in normal and neoplastic tissues, a tissue microarray containing 13,447 samples from 147 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.

Results
KLK7 positivity was found in 64 of 147 tumor categories, including 17 tumor categories with at least one strongly positive case. The highest rate of KLK7 positivity was found in squamous cell carcinomas from various sites of origin (positive in 18.1%-63.8%), ovarian and endometrium cancers (4.8%-56.2%), salivary gland tumors (4.8%-13.7%), bilio-pancreatic adenocarcinomas (20.0%-40.4%), and adenocarcinomas of the upper gastrointestinal tract (3.3%-12.5%). KLK7 positivity was linked to nodal metastasis (p = 0.0005), blood vessel infiltration (p = 0.0037), and lymph vessel infiltration (p < 0.0001) in colorectal adenocarcinoma, nodal metastasis in hepatocellular carcinoma (p = 0.0382), advanced pathological tumor stage in papillary thyroid cancer (p = 0.0132), and low grade of malignancy in a cohort of 719 squamous cell carcinomas from 11 different sites of origin (p < 0.0001).

Conclusions
These data provide a comprehensive overview on KLK7 expression in normal and neoplastic human tissues. The prognostic relevance of KLK7 expression and the possible role of KLK7 as a drug target need to be further investigated.
Barriers and facilitators to healthy eating in disadvantaged adults living in the UK: a scoping review
Authors: Briazu Raluca A. , Masood Fatima , Hunt Louise , Pettinger Clare , Wagstaff Carol , McCloy Rachel 
Published: July 2024

AbstractIn the UK people living in disadvantaged communities are less likely than those with higher socio-economic status to have a healthy diet. To address this inequality, it is crucial scientists, practitioners and policy makers understand the factors that hinder and assist healthy food choice in these individuals. In this scoping review, we aimed to identify barriers and facilitators to healthy eating among disadvantaged individuals living in the UK. Additionally, we used the Theoretical Domains Framework (TDF) to synthesise results and provide a guide for the development of theory-informed behaviour change interventions. Five databases were searched, (CINAHL, Embase, MEDLINE, PsycINFO, and Web of Science) for articles assessing healthy dietary intake of disadvantaged adults living in the UK. A total of 50 papers (34 quantitative; 16 qualitative) were included in this review. Across all studies we identified 78 barriers and 49 facilitators found to either impede and/or encourage healthy eating. Both barriers and facilitators were more commonly classified under the Environmental, Context and Resources TDF domain, with 74% of studies assessing at least one factor pertaining to this domain. Results thus indicate that context related factors such as high cost and accessibility of healthy food, rather than personal factors, such as lack of efficiency in healthy lifestyle drive unhealthy eating in disadvantaged individuals in the UK. We discuss how such factors are largely overlooked in current interventions and propose that more effort should be directed towards implementing interventions that specifically target infrastructures rather than individuals.
Predicting dyslipidemia incidence: unleashing machine learning algorithms on Lifestyle Promotion Project data
Authors: Naderian Senobar , Nikniaz Zeinab , Farhangi Mahdieh Abbasalizad , Nikniaz Leila , Sama-Soltani Taha , Rostami Parisa 
Published: July 2024

Abstract
Background
Dyslipidemia, characterized by variations in plasma lipid profiles, poses a global health threat linked to millions of deaths annually.

Objectives
This study focuses on predicting dyslipidemia incidence using machine learning methods, addressing the crucial need for early identification and intervention.

Methods
The dataset, derived from the Lifestyle Promotion Project (LPP) in East Azerbaijan Province, Iran, undergoes a comprehensive preprocessing, merging, and null handling process. Target selection involves five distinct dyslipidemia-related variables. Normalization techniques and three feature selection algorithms are applied to enhance predictive modeling.

Result
The study results underscore the potential of different machine learning algorithms, specifically multi-layer perceptron neural network (MLP), in reaching higher performance metrics such as accuracy, F1 score, sensitivity and specificity, among other machine learning methods. Among other algorithms, Random Forest also showed remarkable accuracies and outperformed K-Nearest Neighbors (KNN) in metrics like precision, recall, and F1 score. The study’s emphasis on feature selection detected meaningful patterns among five target variables related to dyslipidemia, indicating fundamental shared unities among dyslipidemia-related factors. Features such as waist circumference, serum vitamin D, blood pressure, sex, age, diabetes, and physical activity related to dyslipidemia.

Conclusion
These results cooperatively highlight the complex nature of dyslipidemia and its connections with numerous factors, strengthening the importance of applying machine learning methods to understand and predict its incidence precisely.
Associations amongst dynamic knee stiffness during gait, quadriceps stiffness, and the incidence of knee osteoarthritis over 24 months: a cohort study with a mediation analysis
Authors: Li Zongpan , Leung Kam-Lun , Huang Chen , Huang Xiuping , Su Shan , Chung Raymond CK , Ding Changhai , Fu Siu-Ngor 
Published: July 2024

Abstract
Background
Decreased strength and increased stiffness of the quadriceps have been associated with a higher risk of developing knee osteoarthritis (OA) in elders. Dynamic joint stiffness (DJS) represents collective resistance from active and passive knee structures for dynamic knee motions. Elevated sagittal knee DJS has been associated with worsening of cartilage loss in knee OA patients. Altered quadriceps properties may affect DJS, which could be a mediator for associations between quadriceps properties and knee OA. Hence, this study aimed to examine whether DJS and quadriceps properties would be associated with the development of clinical knee OA over 24 months, and to explore the mediation role of DJS in associations between quadriceps properties and knee OA.

Methods
This was a prospective cohort study with 162 healthy community-dwelling elders. Gait analysis was conducted to compute DJS during the loading response phase. Quadriceps strength and stiffness were evaluated using a Cybex dynamometer and shear-wave ultrasound elastography, respectively. Knee OA was defined based on clinical criteria 24 months later. Logistic regression with generalized estimating equations was used to examine the association between quadriceps properties and DJS and incident knee OA. Mediation analysis was performed to explore the mediation role of DJS in associations between quadriceps properties and the incidence of knee OA.

Results
A total of 125 participants (65.6 ± 4.0 years, 58.4% females) completed the 24-month follow-up, with 36 out of 250 knees identified as clinical knee OA. Higher DJS (OR = 1.86, 95%CI: 1.33–2.62), lower quadriceps strength (1.85, 1.05–3.23), and greater quadriceps stiffness (1.56, 1.10–2.21) were significantly associated with a higher risk of clinical knee OA. Mediation analysis showed that the DJS was not a significant mediator for the associations between quadriceps properties and knee OA.

Conclusions
Higher sagittal knee dynamic joint stiffness, lower quadriceps strength, and greater quadriceps stiffness are potential risk factors for developing clinical knee OA in asymptomatic elders. Associations between quadriceps properties and knee OA may not be mediated by dynamic joint stiffness. Interventions for reducing increased passive properties of the quadriceps and knee joint stiffness may be beneficial for maintaining healthy knees in the aging population.