bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data-driven decision-making for precision diagnosis of digestive diseases
Authors: Jiang Song , Wang Ting , Zhang Kun-He 
Published: September 2023

AbstractModern omics technologies can generate massive amounts of biomedical data, providing unprecedented opportunities for individualized precision medicine. However, traditional statistical methods cannot effectively process and utilize such big data. To meet this new challenge, machine learning algorithms have been developed and applied rapidly in recent years, which are capable of reducing dimensionality, extracting features, organizing data and forming automatable data-driven clinical decision systems. Data-driven clinical decision-making have promising applications in precision medicine and has been studied in digestive diseases, including early diagnosis and screening, molecular typing, staging and stratification of digestive malignancies, as well as precise diagnosis of Crohn's disease, auxiliary diagnosis of imaging and endoscopy, differential diagnosis of cystic lesions, etiology discrimination of acute abdominal pain, stratification of upper gastrointestinal bleeding (UGIB), and real-time diagnosis of esophageal motility function, showing good application prospects. Herein, we reviewed the recent progress of data-driven clinical decision making in precision diagnosis of digestive diseases and discussed the limitations of data-driven decision making after a brief introduction of methods for data-driven decision making.
Exploring equity in cancer treatment, survivorship, and service utilisation for culturally and linguistically diverse migrant populations living in Queensland, Australia: a retrospective cohort study
Authors: Scanlon Brighid , Durham Jo , Wyld David , Roberts Natasha , Toloo Ghasem Sam 
Published: September 2023

Abstract
Background
There is strong international evidence documenting inequities in cancer care for migrant populations. In Australia, there is limited information regarding cancer equity for Culturally and Linguistically Diverse (CALD) migrant populations, defined in this study as migrants born in a country or region where English is not the primary language. This study sought to quantify and compare cancer treatment, survivorship, and service utilisation measures between CALD migrant and Australian born cancer populations.

Methods
A retrospective cohort study was conducted utilising electronic medical records at a major, tertiary hospital. Inpatient and outpatient encounters were assessed for all individuals diagnosed with a solid tumour malignancy in the year 2016 and followed for a total of five years. Individuals were screened for inclusion in the CALD migrant or Australian born cohort. Bivariate analysis and multivariate logistic regression were used to compare treatment, survivorship, and service utilisation measures. Sociodemographic measures included age, sex, post code, employment, region of birth and marital status.

Results
A total of 523 individuals were included, with 117 (22%) in the CALD migrant cohort and 406 (78%) in the Australian-born cohort. CALD migrants displayed a statistically significant difference in time from diagnosis to commencement of first treatment for radiation (P = 0.03) and surgery (P = 0.02) and had 16.6 times higher odds of declining recommended chemotherapy than those born in Australia (P = 0.00). Survivorship indicators favoured CALD migrants in mean time from diagnosis to death, however their odds of experiencing disease progression during the study period were 1.6 times higher than those born in Australia (P = 0.04). Service utilisation measures displayed that CALD migrants exhibited higher numbers of unplanned admissions (P = < 0.00), longer cumulative length of those admissions (P = < 0.00) and higher failure to attend scheduled appointments (P = < 0.00).

Conclusion
This novel study has produced valuable findings in the areas of treatment, survivorship, and service utilisation for a neglected population in cancer research. The differences identified suggest potential issues of institutional inaccessibility. Future research is needed to examine the clinical impacts of these health differences in the field of cancer care, including the social and institutional determinants of influence.
Interplay of chronic obstructive pulmonary disease and colorectal cancer development: unravelling the mediating role of fatty acids through a comprehensive multi-omics analysis
Authors: Zhou Youtao , Lin Zikai , Xie Shuojia , Gao Yuan , Zhou Haobin , Chen Fengzhen , Fu Yuewu , Yang Cuiyan , Ke Chuanfeng 
Published: September 2023

Abstract
Background
Chronic obstructive pulmonary disease (COPD) patients often exhibit gastrointestinal symptoms, A potential association between COPD and Colorectal Cancer (CRC) has been indicated, warranting further examination.

Methods
In this study, we collected COPD and CRC data from the National Health and Nutrition Examination Survey, genome-wide association studies, and RNA sequence for a comprehensive analysis. We used weighted logistic regression to explore the association between COPD and CRC incidence risk. Mendelian randomization analysis was performed to assess the causal relationship between COPD and CRC, and cross-phenotype meta-analysis was conducted to pinpoint crucial loci. Multivariable mendelian randomization was used to uncover mediating factors connecting the two diseases. Our results were validated using both NHANES and GEO databases.

Results
In our analysis of the NHANES dataset, we identified COPD as a significant contributing factor to CRC development. MR analysis revealed that COPD increased the risk of CRC onset and progression (OR: 1.16, 95% CI 1.01–1.36). Cross-phenotype meta-analysis identified four critical genes associated with both CRC and COPD. Multivariable Mendelian randomization suggested body fat percentage, omega-3, omega-6, and the omega-3 to omega-6 ratio as potential mediating factors for both diseases, a finding consistent with the NHANES dataset. Further, the interrelation between fatty acid-related modules in COPD and CRC was demonstrated via weighted gene co-expression network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment results using RNA expression data.

Conclusions
This study provides novel insights into the interplay between COPD and CRC, highlighting the potential impact of COPD on the development of CRC. The identification of shared genes and mediating factors related to fatty acid metabolism deepens our understanding of the underlying mechanisms connecting these two diseases.
Suppressive stroma-immune prognostic signature impedes immunotherapy in ovarian cancer and can be reversed by PDGFRB inhibitors
Authors: Yang Dong , Duan Mei-Han , Yuan Qiu-Er , Li Zhi-Ling , Luo Chuang-Hua , Cui Lan-Yue , Li Li-Chao , Xiao Ying , Zhu Xian-Ying , Zhang Hai-Liang , Feng Gong-Kan , Liu Guo-Chen , Deng Rong , Li Jun-Dong , Zhu Xiao-Feng 
Published: September 2023

Abstract
Background
As the most lethal gynecologic cancer, ovarian cancer (OV) holds the potential of being immunotherapy-responsive. However, only modest therapeutic effects have been achieved by immunotherapies such as immune checkpoint blockade. This study aims to propose a generalized stroma-immune prognostic signature (SIPS) to identify OV patients who may benefit from immunotherapy.

Methods
The 2097 OV patients included in the study were significant with high-grade serous ovarian cancer in the III/IV stage. The 470 immune-related signatures were collected and analyzed by the Cox regression and Lasso algorithm to generalize a credible SIPS. Correlations between the SIPS signature and tumor microenvironment were further analyzed. The critical immunosuppressive role of stroma indicated by the SIPS was further validated by targeting the major suppressive stroma component (CAFs, Cancer-associated fibroblasts) in vitro and in vivo. With four machine-learning methods predicting tumor immune subtypes, the stroma-immune signature was upgraded to a 23-gene signature.

Results
The SIPS effectively discriminated the high-risk individuals in the training and validating cohorts, where the high SIPS succeeded in predicting worse survival in several immunotherapy cohorts. The SIPS signature was positively correlated with stroma components, especially CAFs and immunosuppressive cells in the tumor microenvironment, indicating the critical suppressive stroma-immune network. The combination of CAFs’ marker PDGFRB inhibitors and frontline PARP inhibitors substantially inhibited tumor growth and promoted the survival of OV-bearing mice. The stroma-immune signature was upgraded to a 23-gene signature to improve clinical utility. Several drug types that suppress stroma-immune signatures, such as EGFR inhibitors, could be candidates for potential immunotherapeutic combinations in ovarian cancer.

Conclusions
The stroma-immune signature could efficiently predict the immunotherapeutic sensitivity of OV patients. Immunotherapy and auxiliary drugs targeting stroma could enhance immunotherapeutic efficacy in ovarian cancer.
Production of a chimeric flavivirus that contains the major structural glycoprotein genes of T’Ho virus in the genetic background of Zika virus
Authors: Tangudu Chandra S. , Hargett Alissa M. , Mitrisin Brooke C. , Laredo-Tiscareño S. Viridiana , Blitvich Bradley J. 
Published: September 2023

AbstractT’Ho virus is a poorly characterized orthoflavivirus most closely related to Rocio virus and Ilheus virus, two orthoflaviviruses associated with human disease, suggesting that T’Ho virus could also be a human pathogen. The genome of T’Ho virus has been sequenced but an isolate has never been recovered, impeding its phenotypic characterization. In an attempt to generate recombinant T’Ho virus, the entire viral genome was synthesized as three overlapping DNA fragments, joined by Gibson assembly, and transfected into mosquito cells. Several cell culture passages were performed, but virus was not recovered. Subsequent experiments focused on the development of a chimeric orthoflavivirus that contains the premembrane and envelope protein genes of T’Ho virus in the genetic background of Zika virus. The chimeric virus replicated in mosquito (C6/36) and vertebrate (Vero) cells, demonstrating that the major structural glycoproteins of T’Ho virus permit entry into both cell types. The chimeric virus produced plaques in Vero cells that were significantly smaller than those produced by Zika virus. The chimeric virus can potentially be used as a surrogate diagnostic reagent in place of T’Ho virus in plaque reduction neutralization tests, allowing T’Ho virus to be considered in the differential diagnosis.
Ethnobotany for food security and ecological transition: wild food plant gathering and consumption among four cultural groups in Kurram District, NW Pakistan
Authors: Hussain Sayed Taufiq , Muhammad Sayed , Khan Sheharyar , Hussain Wahid , Pieroni Andrea 
Published: September 2023

Abstract
Background
In traditional food systems, especially those of rural populations around the world, wild food plants remain crucial. These resources need to be urgently documented to lay the foundations for sustainable livelihoods and food security.

Methods
In the present field study, we gathered information about wild food plants and mushrooms consumed by four ethnic groups (Turis, Khushis, Hazaras, and Christians) living in Kurram District, NW Pakistan, by conducting semi-structured interviews and holding group discussions.

Results
A total of 57 wild edible plants and mushrooms were reported, with the documented taxa belonging to 50 genera and 34 families. Turis reported the highest number of wild food plants (41), followed by Hazaras (37), Khushis (35), and then Christians, who reported only 11 plants. The most dominant families were Rosaceae, followed by Polygonaceae, Brassicaceae, Fabaceae, Lamiaceae, Moraceae, and Plantaginaceae. The comparative analysis we conducted with the pre-existing Pakistani ethnobotanical studies revealed that 23 wild edible plants have not been previously reported as food items in the area under study, which included Fragaria nubicola, Lepidium draba, Pinus wallichiana, Podophyllum emodi, Prunus jacquemontii, Sambucus nigra, Sideroxylon mascatense, and Thymus linearis. Four wild edible mushrooms are also reported for the area for the first time: Calvatia gigantea, Morchella esculenta, Pisolithus albus, and Tulostoma squamosum. The cross-cultural analysis of wild edible plants and their uses revealed remarkable similarity between Khushis and Hazaras. The overlapping pattern of wild edible plant use among these two groups, as well as Turis, confirms the existence of cross-cultural interactions among these communities, which have shared the same environmental and socio-cultural space for several decades. Food heritage and some unique dishes are linked to wild edible plants in the area, such as Zamda, prepared by Turis, and Saba, famous among Khushis and Hazaras.

Conclusion
This study suggests that some wild edible plants could be cultivated to protect a few threatened species from overexploitation, while the overall wild food plant heritage should be promoted and revitalized; for example, within educational platforms aimed at improving the wellbeing of local communities and the global ecological transition we must deal with.
Drugs involved in Kentucky drug poisoning deaths and relation with antecedent controlled substance prescription dispensing
Authors: Freeman Patricia R. , McAninch Jana , Dasgupta Nabarun , Oyler Douglas R. , Slavov Krassimir , Collins Candice , Hargrove Sarah , Freeman Edward , Miracle Dustin , Slavova Svetla 
Published: September 2023

Abstract
Background
The shift from prescription to illicit drugs involved in drug poisoning deaths raises questions about the current utility of prescription drug monitoring program (PDMP) data to inform drug poisoning (overdose) prevention efforts. In this study, we describe relations between specific drugs involved in Kentucky drug poisoning deaths and antecedent controlled substance (CS) dispensing.

Methods
The study used linked death certificates and PDMP data for 2,248 Kentucky resident drug poisoning deaths in 2021. Death certificate literal text analysis identified drugs mentioned with involvement (DMI) in drug poisoning deaths. We characterized the concordance between each DMI and the CS dispensing history for this drug at varying timepoints since 2008.

Results
Overall, 25.5% of all decedents had dispensed CS in the month before fatal drug poisoning. Over 80% of decedents were dispensed opioid(s) since 2008; the percentage was similar regardless of opioid involvement in the poisoning death. One-third of decedents had dispensed buprenorphine for treatment of opioid use disorder since 2008, but only 6.1% had dispensed buprenorphine in the month preceding death. Fentanyl/fentanyl analogs were DMI in 1,568 (69.8%) deaths, yet only 3% had received a fentanyl prescription since 2008. The highest concordance in the month preceding death was observed for clonazepam (43.6%).

Conclusion
Overall, concordance between CS dispensing history and the drugs involved in poisoning deaths was low, suggesting a need to reevaluate the complex relationships between prescription medication exposure and overdose death and to expand harm reduction interventions both within and outside the healthcare system to reduce drug poisoning mortality.
Composite endpoints, including patient reported outcomes, in rare diseases
Authors: Verbeeck Johan , Dirani Maya , Bauer Johann W. , Hilgers Ralf-Dieter , Molenberghs Geert , Nabbout Rima 
Published: September 2023

Abstract
Background
When assessing the efficacy of a treatment in any clinical trial, it is recommended by the International Conference on Harmonisation to select a single meaningful endpoint. However, a single endpoint is often not sufficient to reflect the full clinical benefit of a treatment in multifaceted diseases, which is often the case in rare diseases. Therefore, the use of a combination of several clinically meaningful outcomes is preferred. Many methodologies that allow for combining outcomes in a so-called composite endpoint are however limited in a number of ways, not in the least in the number and type of outcomes that can be combined and in the poor small-sample properties. Moreover, patient reported outcomes, such as quality of life, often cannot be integrated in a composite analysis, in spite of their intrinsic value.

Results
Recently, a class of non-parametric generalized pairwise comparisons tests have been proposed, which members do allow for any number and type of outcomes, including patient reported outcomes. The class enjoys good small-sample properties. Moreover, this very flexible class of methods allows for prioritizing the outcomes by clinical severity, allows for matched designs and for adding a threshold of clinical relevance. Our aim is to introduce the generalized pairwise comparison ideas and concepts for rare disease clinical trial analysis, and demonstrate their benefit in a post-hoc analysis of a small-sample trial in epidermolysis bullosa. More precisely, we will include a patient relevant outcome (Quality of life), in a composite endpoint. This publication is part of the European Joint Programme on Rare Diseases (EJP RD) series on innovative methodologies for rare diseases clinical trials, which is based on the webinars presented within the educational activity of EJP RD. This publication covers the webinar topic on composite endpoints in rare diseases and includes participants’ response to a questionnaire on this topic.

Conclusions
Generalized pairwise comparisons is a promising statistical methodology for evaluating any type of composite endpoints in rare disease trials and may allow a better evaluation of therapy efficacy including patients reported outcomes in addition to outcomes related to the diseases signs and symptoms.
Infant and Young Child Feeding practices up to 23 months in Namuno District, Cabo Delgado, Mozambique
Authors: Marroda Kodak Raúl , Berti Cristiana , La Vecchia Adriano , Agostoni Carlo , Baroni Bruno Nazim , Bettocchi Silvia , Baglioni Mattia 
Published: September 2023

Abstract
Background
Inadequate breastfeeding and complementary feeding practices are key determinants of child malnutrition and impact one-third of the under-five mortality rate worldwide. The district of Namuno in Cabo Delgado (Mozambique) has been long registering a high prevalence of acute malnutrition. To date, no data exists about Infant and Young Child Feeding (IYCF) practices in the area. The current pilot study explores the feeding practices among children aged 0–23 months in Namuno and sets out its main drivers.

Methods
This cross-sectional study was realized between August and September 2019 and drew on questionnaires for mothers/caregivers of children aged 0 to 23 months. We computed IYCF indicators and correlated them with mothers’/caregivers' school attendance, delivery setting, and distance between home and the place where livelihood activities took place (workplace), using univariate and multivariate (age-adjusted) logistic regression analysis.

Results
The survey was data derived from a sample of 632 mothers/caregivers. 62% of 0–23-month-old children received colostrum whilst only 31% of 0–5 months babies were on exclusive breastfeeding (EBF). Among 6–23 months old children, 17% consumed foods and beverages from at least five out of eight defined food groups, 31% received a minimum frequency of meals, and 23% had a minimum acceptable diet. Data revealed a positive correlation between early initiation of breastfeeding and delivery in a maternity ward (OR 6.9, CI 3.2–16.1, p-value < 0.001). No difference in the IYCF indicators between female and male babies was detected.

Conclusions
In the Namuno district, IYCF practices did not fulfill WHO/UNICEF’s indicators and recommendations. This suggests that efforts should be focused on EBF-enabling interventions to improve children’s dietary consumption patterns.
Effectiveness and safety of mesenchymal stem/stromal cell for radiation-induced hyposalivation and xerostomia in previous head and neck cancer patients (MESRIX-III): a study protocol for a single-centre, double-blinded, randomised, placebo-controlled, phase II study
Authors: Jakobsen Kathrine Kronberg , Carlander Amanda-Louise Fenger , Grønhøj Christian , Todsen Tobias , Melchiors Jacob , Paaske Natasja , Madsen Anne Kathrine Østergaard , Kastrup Jens , Ekblond Annette , Haack-Sørensen Mandana , Farhadi Mohammad , Maare Christian , Friborg Jeppe , Lynggard Charlotte Duch , von Buchwald Christian 
Published: September 2023

Abstract
Background
A predominant side effect of radiotherapy for head and neck cancer is salivary gland hypofunction and xerostomia leading to debilitating oral disorders and impaired quality of life (QoL). Intraglandular mesenchymal stem cell therapy has shown promising results as a treatment for xerostomia.

Methods
This is a randomised, double-blinded, placebo-controlled, parallel-group, prospective, single-centre trial investigating the safety, tolerability, and effectiveness of allogeneic stem cells as a treatment for radiation-induced hyposalivation and xerostomia for previous head and neck cancer patients.
We will include a total of 120 patients who previously have been treated with radiotherapy for a head and neck cancer in Denmark. Participants will be randomly assigned using block randomisation to one of two parallel groups in a 1:1 ratio to receive ultrasound-guided injection of allogeneic adipose-derived mesenchymal stem cell (ASC) (n = 60) or placebo (n = 60) into the submandibular glands. Placebo will consist of CryoStor10 (BiolifeSolutions), the freeze media for ASCs containing 10% dimethyl sulfoxide (DMSO). The primary endpoint is change in unstimulated whole saliva flow rate. The secondary endpoints are change in stimulated whole saliva flow rate, QoL, and composition of saliva. Further secondary endpoints are safety and immune response (human leukocyte antigen (HLA) response) to the stem cells will be assessed. Patients are evaluated at baseline (before treatment), after 4 months, and after 12 months. All study personnel, except study personnel thawing and preparing the treatment for injection, and participants will be blinded to group assignment. Unblinded study personnel will not participate in the outcome assessment.

Discussion
The trials will investigate the efficacy and safety of ASC injection to the submandibular gland as a potential new treatment for post-radiation xerostomia. We hope the results will pave the way for a clinically relevant treatment to ameliorate patients with xerostomia, a severely hampering condition.

Trial registration
The study is approved by the Danish Data Protection Agency (protocol number P-2020-1164), the National Ethics Committee protocol number: (Protocol number: 1802872), and the Danish Medical Agency (2018-000348-24). The protocol was registered at the ClinicalTrials.gov database (NCT04776538).