bluuebunny/crossref_metadata_2025_split huggingface dataset:
Second malignancies among older patients with classical myeloproliferative neoplasms treated with hydroxyurea
Authors: Wang Rong , Shallis Rory M. , Stempel Jessica M. , Huntington Scott F. , Zeidan Amer M. , Gore Steven D. , Ma Xiaomei , Podoltsev Nikolai A. 
Published: August 2022

Abstract
Patients with classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary and secondary myelofibrosis (MF), are known to have an increased risk of second malignancies (SMs). Hydroxyurea (HU) is a guideline-recommended cytoreductive therapy for patients at high risk for MPNs. Controversy exists as to whether HU use is associated with a higher risk of SMs, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We conducted a retrospective cohort study of older patients diagnosed with MPN (age ≥66 years) between 2010 and 2017 and included the data in the Surveillance, Epidemiology, and End Results Medicare-linked database. Multivariable competing risk analyses adjusting for patient characteristics were used to assess the impact of HU on the development of SM. We identified 4023 patients (1688 with PV, 1976 with ET, and 359 with MF) with a median age of 77 (interquartile range [IQR], 71-83) years at the time of MPN diagnosis. After a median follow-up of 3.25 (IQR, 2.10-5.00) years, 489 patients developed an SM (346 solid, 73 lymphoid, and 70 myeloid malignancies). The cumulative incidence probability of SM was 19.88% (95% confidence interval [CI], 17.16%-22.75%) among 2683 HU users and 22.31% (95% CI, 17.51%-27.47%) among 1340 nonusers, respectively (Gray’s test, P &lt; .01). We did not identify significant differences in the incidence of solid or hematologic SMs, including AML/MDS (hazard ratio, 1.33; 95% CI, 0.77-2.29; P = .30), between HU users and nonusers. Our results suggest that the use of HU does not increase the risk of SM in older patients with MPN.
In silico design of a multi-epitope vaccine against HPV16/18
Authors: Sanami Samira , Rafieian-Kopaei Mahmoud , Dehkordi Korosh Ashrafi , Pazoki-Toroudi Hamidreza , Azadegan-Dehkordi Fatemeh , Mobini Gholam-Reza , Alizadeh Morteza , Nezhad Muhammad Sadeqi , Ghasemi-Dehnoo Maryam , Bagheri Nader 
Published: August 2022

Abstract
Background
Cervical cancer is the fourth most common cancer affecting women and is caused by human Papillomavirus (HPV) infections that are sexually transmitted. There are currently commercially available prophylactic vaccines that have been shown to protect vaccinated individuals against HPV infections, however, these vaccines have no therapeutic effects for those who are previously infected with the virus. The current study’s aim was to use immunoinformatics to develop a multi-epitope vaccine with therapeutic potential against cervical cancer.

Results
In this study, T-cell epitopes from E5 and E7 proteins of HPV16/18 were predicted. These epitopes were evaluated and chosen based on their antigenicity, allergenicity, toxicity, and induction of IFN-γ production (only in helper T lymphocytes). Then, the selected epitopes were sequentially linked by appropriate linkers. In addition, a C-terminal fragment of Mycobacterium tuberculosis heat shock protein 70 (HSP70) was used as an adjuvant for the vaccine construct. The physicochemical parameters of the vaccine construct were acceptable. Furthermore, the vaccine was soluble, highly antigenic, and non-allergenic. The vaccine’s 3D model was predicted, and the structural improvement after refinement was confirmed using the Ramachandran plot and ProSA-web. The vaccine’s B-cell epitopes were predicted. Molecular docking analysis showed that the vaccine's refined 3D model had a strong interaction with the Toll-like receptor 4. The structural stability of the vaccine construct was confirmed by molecular dynamics simulation. Codon adaptation was performed in order to achieve efficient vaccine expression in Escherichia coli strain K12 (E. coli). Subsequently, in silico cloning of the multi-epitope vaccine was conducted into pET-28a ( +) expression vector.

Conclusions
According to the results of bioinformatics analyses, the multi-epitope vaccine is structurally stable, as well as a non-allergic and non-toxic antigen. However, in vitro and in vivo studies are needed to validate the vaccine’s efficacy and safety. If satisfactory results are obtained from in vitro and in vivo studies, the vaccine designed in this study may be effective as a therapeutic vaccine against cervical cancer.
Involvement of MdWRKY40 in the defense of mycorrhizal apple against fusarium solani
Authors: Wang Mei , Tang Weixiao , Xiang Li , Chen Xuesen , Shen Xiang , Yin Chengmiao , Mao Zhiquan 
Published: August 2022

Abstract
Background
Apple (Malus domestica Borkh.) is an important economic crop. The pathological effects of Fusarium solani, a species complex of soilborne pathogens, on the root systems of apple plants was unknown. It was unclear how mycorrhizal apple seedlings resist infection by F. solani. The transcriptional profiles of mycorrhizal and non-mycorrhizal plants infected by F. solani were compared using RNA-Seq.

Results
Infection with F. solani significantly reduced the dry weight of apple roots, and the roots of mycorrhizal apple plants were less damaged when the plants were infected with F. solani. They also had enhanced activity of antioxidant enzymes and a reduction in the oxidation of membrane lipids. A total of 1839 differentially expressed genes (DEGs) were obtained after mycorrhizal and non-mycorrhizal apple plants were infected with F. solani. A gene ontogeny (GO) analysis showed that most of the DEGs were involved in the binding of ADP and calcium ions. In addition, based on a MapMan analysis, a large number of DEGs were found to be involved in the response of mycorrhizal plants to stress. Among them, the overexpressed transcription factor MdWRKY40 significantly improved the resistance of the apple ‘Orin’ callus to F. solani and the expression of the resistance gene MdGLU by binding the promoter of MdGLU.

Conclusion
This paper outlines how the inoculation of apple seedlings roots by arbuscular mycorrhizal fungi responded to infection with F. solani at the transcriptional level. In addition, MdWRKY40 played an important role in the resistance of mycorrhizal apple seedlings to infection with F. solani.
COVID-19 pandemic partnership between medical students and isolated elders improves student understanding of older adults’ lived experience
Authors: Moonen Gray , Perrier Laure , Meiyappan Soumia , Akhtar Sabrina , Crampton Noah 
Published: August 2022

Abstract
Background
Evidence supports loneliness and social isolation as a strong risk factor for poor mental and physical health outcomes for older adults. The COVID-19 pandemic necessitated older adults isolate themselves for a prolonged duration. The Faculty of Medicine at the University of Toronto established the Student-Senior Isolation Prevention Partnership (SSIPP), a volunteer program involving telephone calls between medical students and older adults.

Methods
A mixed methods pre-post study design included collecting quantitative data from older adults using the UCLA Loneliness Scale and the Warwick-Edinburgh Mental Well-being Scale. The study included 29 medical students and 47 older adults. The medical students filled out a questionnaire on self-perceived knowledge of social isolation, perception of seniors, attitudes towards seniors, and likelihood to engage in specialties focusing on older adults. Interviews were conducted with both the older adults and the medical students to understand each groups’ experiences and perspectives with taking part in the SSIPP program.

Results
Participation in the program resulted in significant changes for medical students in areas such as increasing their likelihood to engage in care for older adults (p < .001), improving their knowledge of social isolation for seniors (p < .001), and the value of addressing social isolation in older adults (p < .001). The interviews conducted with the medical students support these findings and provide insight into contributing factors. Loneliness and mental well-being scales did not show significant changes for older adults however, our interviews revealed they considered the program to be valuable.

Conclusions
Our results showed that after the communication outreach program, medical students’ perceptions were positively influenced towards older adults and they were more likely to pursue a career concentrated on older adults. The qualitative analysis revealed older adults valued the program. Timing and consistency of calls were factors identified by this group as having practical importance.
Factors associated with COVID-19 vaccine uptake among French population aged 65 years and older: results from a national online survey
Authors: Jung Yu-Jin , Gagneux-Brunon Amandine , Bonneton Marion , Botelho-Nevers Elisabeth , Verger Pierre , Ward Jeremy K. , Launay Odile 
Published: August 2022

Abstract
Background
In France, the increase in COVID-19 vaccine uptake among older adults slowed down between May and June 2021. Using the data from a national survey, we aimed to assess COVID-19 vaccine uptake among French residents aged 65 years and older, particularly at risk of severe form of the infection, and identify factors associated with non-vaccination.

Methods
A cross-sectional online survey collected the immunization status/intention to get the COVID-19 vaccine, reasons for vaccination/non-vaccination and factors potentially associated with vaccine uptake between May 10 and 23, 2021 among a large sample of French residents. Characteristics of participants were compared according to immunization status. Factors potentially associated with non-vaccination were computed into a multivariate logistic regression.

Results
Among the 1941 survey participants, 1612 (83%) reported having received at least one dose of COVID-19 vaccine. Among the 329 unvaccinated, 197 (60%) declared having the intention to get vaccinated. Younger age (adjusted odds ratio (aOR) = 1.50; 95% confidence interval (CI), 1.05–2.14), thinking previously having COVID-19 (aOR = 4.01; 95% CI, 2.17–7.40), having suffered economic impact due to the pandemic (aOR = 2.63; 95% CI, 1.71–4.04), reporting an “unsafe” opinion about COVID-19 vaccine safety (aOR = 6.79; 95% CI, 4.50–10.26), reporting an “unsupportive” opinion about vaccination in general (aOR = 4.24; 95% CI, 2.77–6.49) were independent risk factors for non-vaccination. On the other hand, trust in COVID-19 vaccine information delivered by the doctor (aOR = 0.28; 95% CI, 0.16–0.48) and trust in the government’s actions (aOR = 0.50; 95% CI, 0.34–0.74) were independent protective factors for non-vaccination. Political affiliation also remained significantly associated with vaccine uptake.

Conclusions
Despite high overall COVID-19 vaccine uptake among the study participants, differences in vaccine uptake according to the level of concerns regarding COVID-19 vaccine safety, socioeconomic profile and trust in the government were observed. Our results reinforce the importance of “reaching out” vaccination strategy that specifically targets the most vulnerable fringe of older adult population.
Depressive symptoms and malnutrition are associated with other geriatric syndromes and increase risk for 30-Day readmission in hospitalized older adults: a prospective cohort study
Authors: Laura Tay , Melvin Chua , Yoong Ding Yew 
Published: August 2022

AbstractBackgroundReadmission in older adults is typically complex with multiple contributing factors. We aim to examine how two prevalent and potentially modifiable geriatric conditions – depressive symptoms and malnutrition – relate to other geriatric syndromes and 30-day readmission in hospitalized older adults.MethodsConsecutive admissions of patients ≥ 65 years to a general medical department were recruited over 16 months. Patients were screened for depression, malnutrition, delirium, cognitive impairment, and frailty at admission. Medical records were reviewed for poor oral intake and functional decline during hospitalization. Unplanned readmission within 30-days of discharge was tracked through the hospital’s electronic health records and follow-up telephone interviews. We use directed acyclic graphs (DAGs) to depict the relationship of depressive symptoms and malnutrition with geriatric syndromes that constitute covariates of interest and 30-day readmission outcome. Multiple logistic regression was performed for the independent associations of depressive symptoms and malnutrition with 30-day readmission, adjusting for variables based on DAG-identified minimal adjustment set.ResultsWe recruited 1619 consecutive admissions, with mean age 76.4 (7.9) years and 51.3% females. 30-day readmission occurred in 331 (22.0%) of 1,507 patients with follow-up data. Depressive symptoms, malnutrition, higher comorbidity burden, hospitalization in the one-year preceding index admission, frailty, delirium, as well as functional decline and poor oral intake during the index admission, were more commonly observed among patients who were readmitted within 30 days of discharge (P < 0.05). Patients with active depressive symptoms were significantly more likely to be frail (OR = 1.62, 95% CI 1.22–2.16), had poor oral intake (OR = 1.35, 95% CI 1.02–1.79) and functional decline during admission (OR = 1.58, 95% CI 1.11–2.23). Malnutrition at admission was significantly associated with frailty (OR = 1.53, 95% CI 1.07–2.19), delirium (OR = 2.33, 95% CI 1.60–3.39) cognitive impairment (OR = 1.88, 95% CI 1.39–2.54) and poor oral intake during hospitalization (OR = 2.70, 95% CI 2.01–3.64). In minimal adjustment set identified by DAG, depressive symptoms (OR = 1.38, 95% CI 1.02–1.86) remained significantly associated with 30-day readmission. The association of malnutrition with 30-day readmission was no longer statistically significant after adjusting for age, ethnicity and depressive symptoms in the minimal adjustment set (OR = 1.40, 95% CI 0.99–1.98).ConclusionThe observed causal associations support screening and targeted interventions for depressive symptoms and malnutrition during admission and in the post-acute period.
Prevalence and associated factors of oligohydramnios in pregnancies beyond 36 weeks of gestation at a tertiary hospital in southwestern Uganda
Authors: Twesigomwe Godfrey , Migisha Richard , Agaba David Collins , Owaraganise Asiphas , Aheisibwe Hillary , Tibaijuka Leevan , Abesiga Lenard , Ngonzi Joseph , Tornes Yarine Fajardo 
Published: August 2022

Abstract
Background
Oligohydramnios is associated with poor maternal and perinatal outcomes. In low-resource countries, including Uganda, oligohydramnios is under-detected due to the scarcity of ultrasonographic services. We determined the prevalence and associated factors of oligohydramnios among women with pregnancies beyond 36 weeks of gestation at Mbarara Regional Referral Hospital (MRRH) in Southwestern Uganda.

Methods
We conducted a hospital-based cross-sectional study from November 2019 to March 2020. Included were women at gestational age > 36 weeks. Excluded were women with ruptured membranes, those in active labour, and those with multiple pregnancies. An interviewer-administered structured questionnaire was used to capture demographic, obstetric, and clinical characteristics of the study participants. We determined oligohydramnios using an amniotic fluid index (AFI) obtained using an ultrasound scan. Oligohydramnios was diagnosed in participants with AFI ≤ 5 cm. We performed multivariable logistic regression to determine factors associated with oligohydramnios.

Results
We enrolled 426 women with a mean age of 27 (SD ± 5.3) years. Of the 426 participants, 40 had oligohydramnios, for a prevalence of 9.4% (95%CI: 6.8–12.6%). Factors found to be significantly associated with oligohydramnios were history of malaria in pregnancy (aOR = 4.6; 95%CI: 1.5–14, P = 0.008), primegravidity (aOR = 3.7; 95%CI: 1.6–6.7, P = 0.002) and increasing gestational age; compared to women at 37–39 weeks, those at 40–41 weeks (aOR = 2.5; 95%CI: 1.1–5.6, P = 0.022), and those at > 41 weeks (aOR = 6.0; 95%CI: 2.3–16, P = 0.001) were more likely to have oligohydramnios.

Conclusion
Oligohydramnios was detected in approximately one out of every ten women seeking care at MRRH, and it was more common among primigravidae, those with a history of malaria in pregnancy, and those with post-term pregnancies. We recommend increased surveillance for oligohydramnios in the third trimester, especially among prime gravidas, those with history of malaria in pregnancy, and those with post-term pregnancies, in order to enable prompt detection of this complication and plan timely interventions. Future longitudinal studies are needed to assess clinical outcomes in women with oligohydramnios in our setting.
Bias and inconsistency in the estimation of tumour mutation burden
Authors: Makrooni Mohammad A. , O’Sullivan Brian , Seoighe Cathal 
Published: August 2022

AbstractBackgroundTumour mutation burden (TMB), defined as the number of somatic mutations per megabase within the sequenced region in the tumour sample, has been used as a biomarker for predicting response to immune therapy. Several studies have been conducted to assess the utility of TMB for various cancer types; however, methods to measure TMB have not been adequately evaluated. In this study, we identified two sources of bias in current methods to calculate TMB.MethodsWe used simulated data to quantify the two sources of bias and their effect on TMB calculation, we down-sampled sequencing reads from exome sequencing datasets from TCGA to evaluate the consistency in TMB estimation across different sequencing depths. We analyzed data from ten cancer cohorts to investigate the relationship between inferred TMB and sequencing depth.ResultsWe found that TMB, estimated by counting the number of somatic mutations above a threshold frequency (typically 0.05), is not robust to sequencing depth. Furthermore, we show that, because only mutations with an observed frequency greater than the threshold are considered, the observed mutant allele frequency provides a biased estimate of the true frequency. This can result in substantial over-estimation of the TMB, when the cancer sample includes a large number of somatic mutations at low frequencies, and exacerbates the lack of robustness of TMB to variation in sequencing depth and tumour purity.ConclusionOur results demonstrate that care needs to be taken in the estimation of TMB to ensure that results are unbiased and consistent across studies and we suggest that accurate and robust estimation of TMB could be achieved using statistical models that estimate the full mutant allele frequency spectrum.
Comparison of mortality prediction models for road traffic accidents: an ensemble technique for imbalanced data
Authors: Boo Yookyung , Choi Youngjin 
Published: August 2022

Abstract
Background
Injuries caused by RTA are classified under the International Classification of Diseases-10 as ‘S00-T99’ and represent imbalanced samples with a mortality rate of only 1.2% among all RTA victims. To predict the characteristics of external causes of road traffic accident (RTA) injuries and mortality, we compared performances based on differences in the correction and classification techniques for imbalanced samples.

Methods
The present study extracted and utilized data spanning over a 5-year period (2013–2017) from the Korean National Hospital Discharge In-depth Injury Survey (KNHDS), a national level survey conducted by the Korea Disease Control and Prevention Agency, A total of eight variables were used in the prediction, including patient, accident, and injury/disease characteristics. As the data was imbalanced, a sample consisting of only severe injuries was constructed and compared against the total sample. Considering the characteristics of the samples, preprocessing was performed in the study. The samples were standardized first, considering that they contained many variables with different units. Among the ensemble techniques for classification, the present study utilized Random Forest, Extra-Trees, and XGBoost. Four different over- and under-sampling techniques were used to compare the performance of algorithms using “accuracy”, “precision”, “recall”, “F1”, and “MCC”.

Results
The results showed that among the prediction techniques, XGBoost had the best performance. While the synthetic minority oversampling technique (SMOTE), a type of over-sampling, also demonstrated a certain level of performance, under-sampling was the most superior. Overall, prediction by the XGBoost model with samples using SMOTE produced the best results.

Conclusion
This study presented the results of an empirical comparison of the validity of sampling techniques and classification algorithms that affect the accuracy of imbalanced samples by combining two techniques. The findings could be used as reference data in classification analyses of imbalanced data in the medical field.
The TROLLEY Study: assessing travel, health, and equity impacts of a new light rail transit investment during the COVID-19 pandemic
Authors: Crist Katie , Benmarhnia Tarik , Frank Lawrence D. , Song Dana , Zunshine Elizabeth , Sallis James F. 
Published: August 2022

Abstract
Background
The COVID-19 pandemic disrupted life in extraordinary ways impacting health and daily mobility. Public transit provides a strategy to improve individual and population health through increased active travel and reduced vehicle dependency, while ensuring equitable access to jobs, healthcare, education, and mitigating climate change. However, health safety concerns during the COVID-19 pandemic eroded ridership, which could have longstanding negative consequences. Research is needed to understand how mobility and health change as the pandemic recedes and how transit investments impact health and equity outcomes.

Methods
The TROLLEY (TRansit Opportunities for HeaLth, Livability, Exercise and EquitY) study will prospectively investigate a diverse cohort of university employees after the opening of a new light rail transit (LRT) line and the easing of campus COVID-19 restrictions. Participants are current staff who live either < 1 mile, 1–2 miles, or  > 2 miles from LRT, with equal distribution across economic and racial/ethnic strata. The primary aim is to assess change in physical activity, travel mode, and vehicle miles travelled using accelerometer and GPS devices. Equity outcomes include household transportation and health-related expenditures. Change in health outcomes, including depressive symptoms, stress, quality of life, body mass index and behavior change constructs related to transit use will be assessed via self-report. Pre-pandemic variables will be retrospectively collected. Participants will be measured at 3 times over 2 years of follow up. Longitudinal changes in outcomes will be assessed using multilevel mixed effects models. Analyses will evaluate whether proximity to LRT, sociodemographic, and environmental factors modify change in outcomes over time.

Discussion
The TROLLEY study will utilize rigorous methods to advance our understanding of health, well-being, and equity-oriented outcomes of new LRT infrastructure through the COVID-19 recovery period, in a sample of demographically diverse adult workers whose employment location is accessed by new transit. Results will inform land use, transportation and health investments, and workplace interventions. Findings have the potential to elevate LRT as a public health priority and provide insight on how to ensure public transit meets the needs of vulnerable users and is more resilient in the face of future health pandemics.

Trial registration
The TROLLEY study was registered at ClinicalTrials.gov (NCT04940481) June 17, 2021, and OSF Registries (https://doi.org/10.17605/OSF.IO/PGEHU) June 24, 2021, prior to participant enrollment.