bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modular and mechanistic changes across stages of colorectal cancer
Authors: Rahiminejad Sara , Maurya Mano R. , Mukund Kavitha , Subramaniam Shankar 
Published: April 2022

Abstract
Background
While mechanisms contributing to the progression and metastasis of colorectal cancer (CRC) are well studied, cancer stage-specific mechanisms have been less comprehensively explored. This is the focus of this manuscript.

Methods
Using previously published data for CRC (Gene Expression Omnibus ID GSE21510), we identified differentially expressed genes (DEGs) across four stages of the disease. We then generated unweighted and weighted correlation networks for each of the stages. Communities within these networks were detected using the Louvain algorithm and topologically and functionally compared across stages using the normalized mutual information (NMI) metric and pathway enrichment analysis, respectively. We also used Short Time-series Expression Miner (STEM) algorithm to detect potential biomarkers having a role in CRC.

Results
Sixteen Thousand Sixty Two DEGs were identified between various stages (p-value ≤ 0.05). Comparing communities of different stages revealed that neighboring stages were more similar to each other than non-neighboring stages, at both topological and functional levels. A functional analysis of 24 cancer-related pathways indicated that several signaling pathways were enriched across all stages. However, the stage-unique networks were distinctly enriched only for a subset of these 24 pathways (e.g., MAPK signaling pathway in stages I-III and Notch signaling pathway in stages III and IV). We identified potential biomarkers, including HOXB8 and WNT2 with increasing, and MTUS1 and SFRP2 with decreasing trends from stages I to IV. Extracting subnetworks of 10 cancer-relevant genes and their interacting first neighbors (162 genes in total) revealed that the connectivity patterns for these genes were different across stages. For example, BRAF and CDK4, members of the Ser/Thr kinase, up-regulated in cancer, displayed changing connectivity patterns from stages I to IV.

Conclusions
Here, we report molecular and modular networks for various stages of CRC, providing a pseudo-temporal view of the mechanistic changes associated with the disease. Our analysis highlighted similarities at both functional and topological levels, across stages. We further identified stage-specific mechanisms and biomarkers potentially contributing to the progression of CRC.
Exploration of mRNAs and miRNA classifiers for various ATLL cancer subtypes using machine learning
Authors: Ghobadi Mohadeseh Zarei , Emamzadeh Rahman , Afsaneh Elaheh 
Published: April 2022

Abstract
Background
Adult T-cell Leukemia/Lymphoma (ATLL) is a cancer disease that is developed due to the infection by human T-cell leukemia virus type 1. It can be classified into four main subtypes including, acute, chronic, smoldering, and lymphoma. Despite the clinical manifestations, there are no reliable diagnostic biomarkers for the classification of these subtypes.

Methods
Herein, we employed a machine learning approach, namely, Support Vector Machine-Recursive Feature Elimination with Cross-Validation (SVM-RFECV) to classify the different ATLL subtypes from Asymptomatic Carriers (ACs). The expression values of multiple mRNAs and miRNAs were used as the features. Afterward, the reliable miRNA-mRNA interactions for each subtype were identified through exploring the experimentally validated-target genes of miRNAs.

Results
The results revealed that miR-21 and its interactions with DAAM1 and E2F2 in acute, SMAD7 in chronic, MYEF2 and PARP1 in smoldering subtypes could significantly classify the diverse subtypes.

Conclusions
Considering the high accuracy of the constructed model, the identified mRNAs and miRNA are proposed as the potential therapeutic targets and the prognostic biomarkers for various ATLL subtypes.
Underdiagnosis of iron deficiency anemia among patients with colorectal cancer: an examination of electronic medical records
Authors: Bhurosy Trishnee , Jishan Anika , Boland Patrick M. , Lee Yen-Han , Heckman Carolyn J. 
Published: April 2022

Abstract
Background
Timely diagnosis and management of iron deficiency anemia (IDA) in colorectal cancer (CRC) patients improves overall quality of life and survival. This study assessed the proportion of CRC patients who were formally diagnosed with IDA and factors that predict a formal diagnosis of IDA and receiving iron therapy.

Methods
We retrieved electronic medical records (EMRs) of CRC patients from a large comprehensive cancer center in the Northeastern part of the United States (n = 499). We abstracted sociodemographic characteristics, relevant laboratory results, IDA diagnosis, and iron supplementation from the EMRs. We assessed relationships between participant characteristics, a diagnosis of IDA and receiving iron therapy through adjusted logistic regressions.

Results
IDA was formally diagnosed in 26 (5.2%) individuals judged by EMR documentation. Only 153 (30.7%) participants had iron laboratory results available. Among the 153 patients with iron panel data available, 113 (73.9%) had iron deficiency. Seventy-six had absolute iron deficiency as shown by ferritin levels below 100 ng/mL and iron saturation less than 20% and 37 had functional iron deficiency as shown by ferritin levels between 100 and 500 ng/mL and iron saturation less than 20%. 12% of all patients had documentation of iron therapy receipt. A formal diagnosis of IDA was not associated with any of the covariates.

Conclusions
Iron deficiency anemia is under-diagnosed among CRC patients and most likely under-documented in clinical notes. Rates of iron repletion are low, suggesting that many patients with IDA are untreated. Future research should explore provider-level and other strategies for improving assessment and diagnosis of IDA among CRC patients.
Virtual reality-based vision therapy versus OBVAT in the treatment of convergence insufficiency, accommodative dysfunction: a pilot randomized controlled trial
Authors: Li Shijin , Tang Angcang , Yang Bi , Wang Jianglan , Liu Longqian 
Published: April 2022

AbstractBackgroundVirtual reality is being increasingly applied in vision therapy. However, the differences in effectiveness, optimal treatment cycle, and prognosis between virtual reality-based vision therapy and traditional therapies remain unknown. The purpose of this study was to compare the effectiveness of virtual reality-based vision therapy and office-based vergence/accommodative therapy in young adults with convergence insufficiency or accommodative dysfunction.MethodsThe patients were randomly assigned to either the virtual reality-based vision therapy group or the office-based vergence/accommodative therapy group. The vision therapy lasted 12 weeks (1 h/week) in both groups. Binocular visual functions (vergence and accommodation) were measured and a subjective questionnaire-based assessment was performed at baseline and after 6 and 12 weeks of therapy.ResultsIn total, 33 patients with convergence insufficiency and 30 with accommodative dysfunction completed the study. After 12 weeks of treatment for convergence insufficiency, the Convergence Insufficiency Symptom Survey score (F2,31 = 13.704, P < 0.001), near point of convergence (F2,31 = 21.774,P < 0.001), positive fusional vergence (F2,31 = 71.766,P < 0.001), and near horizontal phoria (F2,31 = 16.482,P < 0.001) improved significantly in both groups. Moreover, the monocular accommodative amplitude (F2,25 = 22.154,P < 0.001) and monocular accommodative facility (F2,25 = 86.164,P < 0.001) improved significantly in both groups after 12 weeks of treatment. A statistically significant difference was observed in monocular accommodative facility (F1,25 = 8.140,P = 0.009) between the two groups, but not in other vergence and accommodative functions (0.098 < P < 0.687).ConclusionVirtual reality-based vision therapy significantly improved binocular vision functions and symptoms in patients with convergence insufficiency and accommodative dysfunction, thereby suggesting its effectiveness as a new optional or additional treatment for young adults with these conditions.Trial registrationThis study was registered at the Chinese Clinical Trials Registry on 16/04/2019 (identifier:ChiCTR1900022556).
Meaningfulness protects from and crisis of meaning exacerbates general mental distress longitudinally
Authors: Schnell Tatjana , Krampe Henning 
Published: April 2022

Abstract
Background
Reactions to the COVID-19 pandemic are diverse, and both mental distress and existential crises can arise. The identification of protective and exacerbating factors and their progress over time is therefore highly relevant. The current study examined longitudinal protective effects of meaningfulness and exacerbating effects of crisis of meaning on general mental distress.

Methods
N = 431 participants from Germany and Austria (mean age: 42 years) completed an online survey in both April/May (T1) and July/August 2020 (T2). After determining temporal stability or changes in meaningfulness, crisis of meaning, and general mental distress (PHQ-4), we examined whether (i) meaningfulness and (ii) crisis of meaning, measured at T1, incrementally predicted PHQ-4 at T2, beyond baseline levels of PHQ-4. We further tested (iii) a within-subject mediation of temporal changes in PHQ-4 by changes in crisis of meaning.

Results
Meaningfulness prospectively predicted lower PHQ-4, and crisis of meaning predicted higher PHQ-4. From the first wave of the pandemic until a slowdown three months later, meaningfulness was stable, and crisis of meaning and PHQ-4 decreased. Changes in crisis of meaning mediated the changes in PHQ-4.

Conclusions
Meaningfulness appears to have a protective, and crisis of meaning an exacerbating effect on psychological distress, as shown here for the time of the first pandemic wave until three months later. Attention to existential experiences of meaningfulness and loss of meaning thus proves relevant to the clinical and public health context. Measures that support meaningfulness will help coping with crises of meaning, which in turn supports overcoming general mental distress.
Effect of interventions for non-emergent medical transportation: a systematic review and meta-analysis
Authors: Shekelle Paul G. , Begashaw Meron M. , Miake-Lye Isomi M. , Booth Marika , Myers Bethany , Renda Andrew 
Published: April 2022

Abstract
Introduction
Transportation is an important social determinant of health. We conducted a systematic review of the associations on health and health care utilization of interventions aimed at reducing barriers to non-emergency transportation and non-medical transportation.

Methods
We searched three databases and the gray literature through mid-January 2022. Included studies needed to assess an intervention targeted at non-emergency or non-medical transportation barriers, report missed (or kept) visits, health care utilization, costs, or health outcomes. Data extraction was performed in duplicate and included information about study design, results, and risk of bias. Primary outcomes were frequency of missed appointments, health care utilization, costs, and health outcomes. Synthesis was both narrative and meta-analytic using a random effects model.

Results
Twelve studies met inclusion criteria, three randomized trials, one controlled trial, and eight observational studies. All included studies had some element of risk of bias. Populations studied usually had chronic or serious health conditions or were poor. Interventions included van rides, bus or taxi vouchers, ride-sharing services, and others. Meta-analysis of seven studies (three trials, four observational studies) yielded a pooled estimate of missed appointments = 0.63 (95% confidence interval [CI] 0.48, 0.83) favoring interventions. Evidence on cost, utilization, and health outcomes were too sparse to support conclusions. Evidence on the effect of non-medical transportation is limited to a single study.

Conclusions and relevance
Interventions aimed at non-emergency transportation barriers to access health care are associated with fewer missed appointments; the association with costs, utilization or health outcomes is insufficiently studied to reach conclusions.
This review was registered in PROSPERO as ID CRD42020201875.
Child marriage among displaced populations – a 2019 study in Kurdistan Region of Iraq
Authors: Goers Matthew , Hunersen Kara , Karim Luqman Saleh , Jeffery Allison , Zedan Ali , Robinson Courtland , Metzler Janna 
Published: April 2022

Abstract
Background
Many of the factors that increase risk of child marriage are common among refugees and internally displaced persons (IDPs). We sought to address the gaps in knowledge surrounding child marriage in displaced and host populations in the Kurdistan Region of Iraq (KRI).

Methods
A multistage cluster sample design was employed collecting data of KRI host communities, Iraqi IDPs, and Syrian refugees. Interviews were conducted in eligible households, requiring at least one adult female and one female adolescent present, addressing views of marriage, demographics and socioeconomic factors. Household rosters were completed to assess WHO indicators, related to child marriage including completed child marriage in females 10–19 and completed risk of previously conducted child marriages in females 20–24.

Results
Interviews were completed in 617 hosts, 664 IDPs, and 580 refugee households, obtaining information on 10,281 household members and 1,970 adolescent females. Overall, 10.4% of girls age 10–19 were married. IDPs had the highest percentage of married 10–19-year-old females (12.9%), compared to the host community (9.8%) and refugees (8.1%). Heads of households with lower overall education had higher percentages of child marriage in their homes; this difference in prevalence was most notable in IDPs and refugees. When the head of the household was unemployed, 14.5% of households had child marriage present compared to 8.0% in those with employed heads of household. Refugees and IDPs had larger percentages of child marriage when heads of households were unemployed (refugees 13.1%, IDPs 16.9%) compared to hosts (11.9%). When asked about factors influencing marriage decisions, respondents predominately cited family tradition (52.5%), family honor (15.7%), money/resources (9.6%), or religion (8.0%). Over a third of those interviewed (38.9%) reported a change in influencing factors on marriage after displacement (or after the arrival of refugees in the area for hosts).

Conclusions
Being an IDP in Iraq, unemployment and lower education were associated with an increase in risk for child marriage. Refugees had similar percentages of child marriage as hosts, though the risk of child marriage among refugees was higher in situations of low education and unemployment. Ultimately, child marriage remains a persistent practice worldwide, requiring continued efforts to understand and address sociocultural norms in low socioeconomic and humanitarian settings.
The Flares of Low back pain with Activity Research Study (FLAReS): study protocol for a case-crossover study nested within a cohort study
Authors: Suri Pradeep , Tanus Adrienne D. , Torres Nikki , Timmons Andrew , Irimia Bianca , Friedly Janna L. , Korpak Anna , Daniels Clinton , Morelli Daniel , Hodges Paul W. , Costa Nathalia , Day Melissa A. , Heagerty Patrick J. , Jensen Mark P. 
Published: April 2022

AbstractBackgroundAlthough it is generally accepted that physical activity and flares of low back pain (LBP) are related, evidence for the directionality of this association is mixed. The Flares of Low back pain with Activity Research Study (FLAReS) takes a novel approach to distinguish the short-term effects of specific physical activities on LBP flares from the cumulative effects of such activities, by conducting a longitudinal case-crossover study nested within a cohort study. The first aim is to estimate the short-term effects (≤ 24 h) of specific physical activities on LBP flares among Veterans in primary care in the Veterans Affairs healthcare system. The second aim is to estimate the cumulative effects of specific activities on LBP-related functional limitations at 1-year follow-up.MethodsUp to 550 adults of working age (18—65 years) seen for LBP in primary care complete up to 36 “Scheduled” surveys over 1-year follow-up, and also complete unscheduled “Flare Window” surveys after the onset of new flares. Each survey asks about current flares and other factors associated with LBP. Surveys also inquire about activity exposures over the 24 h, and 2 h, prior to the time of survey completion (during non-flare periods) or prior to the time of flare onset (during flares). Other questions evaluate the number, intensity, duration, and/or other characteristics of activity exposures. Other exposures include factors related to mood, lifestyle, exercise, concurrent treatments, and injuries. Some participants wear actigraphy devices for weeks 1–4 of the study. The first aim will examine associations between 10 specific activity categories and participant-reported flares over 1-year follow-up. The second aim will examine associations between the frequency of exposure to 10 activity categories over weeks 1–4 of follow-up and long-term functional limitations at 12 months. All analyses will use a biopsychosocial framework accounting for potential confounders and effect modifiers.DiscussionFLAReS will provide empirically derived estimates of both the short-term and cumulative effects of specific physical activities for Veterans with LBP, helping to better understand the role of physical activities in those with LBP.Trial RegistrationClinicalTrials.govNCT04828330, registered April 2, 2021.
A novel model of traumatic femoral head necrosis in rats developed by microsurgical technique
Authors: Lv Yongxiang , Qiu Xing , Liu Gang , Wang Yunqing , Zhang Yazhong , Li Wenbo , Zhu Ziqiang 
Published: April 2022

Abstract
Background
Clinical angiography and vascular microperfusion confirmed that the femoral head retains blood supply after a collum femur fracture. However, no animal model accurately mimics this clinical situation. This study was performed to establish a rat model with retained viability of the femoral head and partial vasculature deprivation-induced traumatic caput femoris necrosis by surgery.

Methods
Thirty rats were randomly divided into three groups (n = 10 per group): normal group, sham-operated group (Control), and ischemic osteonecrosis group. The femoral head of the normal group of rats underwent a gross anatomy study and microangiography to identify femoral head blood supply. Microsurgical techniques were used to cauterize the anterior-superior retinacular vessels to induce osteonecrosis. Hematoxylin and Eosin (H&E) staining were used for femoral head histologic assessment. Morphologic assessments of the deformity in and trabecular bone parameters of the femoral head epiphysis were performed using micro-CT.

Results
The blood supply of the femoral head in rats primarily came from the anterior-superior, inferior, and posterior retinacular arteries. However, anterior-superior retinacular vasculature deprivation alone was sufficient in inducing femoral head osteonecrosis. H&E showed bone cell loss in nuclear staining, disorganized marrow, and trabecular structure. The bone volume (BV) decreased by 13% and 22% in the ischemic group after 5 and 10 weeks, respectively. The mean trabecular thickness (Tb.Th) decreased from 0.09 to 0.06 mm after 10 weeks. The trabecular spacing (Tb.Sp) increased from 0.03 to 0.05 mm after 5 weeks, and the epiphyseal height-to-diameter (H/D) ratio decreased.

Conclusions
We developed an original and highly selective rat model that embodied femoral head traumatic osteonecrosis induced by surgical anterior-superior retinacular vasculature deprivation.
Conversion of failed proximal femoral nail antirotation to uncemented or cemented femoral component fixation: a multicentre retrospective study with a median 10-year follow-up
Authors: Shi Wenbo , Zhang Yaodong , Xu Yangkai , Zeng Xianshang , Fu Hongjing , Yu Weiguang 
Published: April 2022

Abstract
Background
Conversion of a failed proximal femoral nail antirotation (PFNA) to a total hip arthroplasty (THA) is becoming increasingly universal. However, consensus has not been reached regarding which device (uncemented or hybrid THA) to use. The aim of this retrospective study was to compare the clinical outcomes of the conversion of failed PFNAs to uncemented versus hybrid THAs in the elderly population.

Methods
Consecutive elderly patients with prior failed PFNAs treated with uncemented or hybrid THA from January 2008 to December 2019 were retrospectively identified from two medical centres. The primary outcome was implant survival after THA revision; secondary outcomes were the functional outcomes assessed using the Harris Hip Score (HHS) and the incidence of key THA-related complications.

Results
A total of 236 patients (uncemented THA, n = 116; hybrid THA, n = 120) were eligible for this study. Kaplan–Meier survival curves demonstrated that the 10-year cumulative survival rates were 0.801 (95% confidence interval [CI], 0.783–0.852) in the uncemented THA group versus 0.925 (95% CI, 0.861–0.964) in the hybrid THA group (hazard ratio [HR] 0.36 [95% CI 0.24–0.56], p = 0.004). From the 72nd month after the revision to the last follow-up, functional outcomes differed considerably between cohorts (each p < 0.05), and the rate of key THA-related complications was comparable between cohorts (p = 0.004).

Conclusion
For elderly patients with prior failed PFNAs who experienced uncemented or hybrid THA, hybrid THA revision may provide a clinically significant improvement over uncemented THA revision with regard to implant survival, functional outcomes, and THA-related complications compared to uncemented THA revision.
Comparison of post-operative bleeding incidence in laser hemorrhoidoplasty with and without hemorrhoidal artery ligation: a double-blinded randomized controlled trial
Authors: Lim Shu Yu , Rajandram Retnagowri , Roslani April Camilla 
Published: April 2022

Abstract
Introduction
The effectiveness of hemorrhoidal artery ligation supplementation in reducing the incidence of post laser hemorrhoidoplasty bleeding has not been investigated.

Methods
This was a double-blind, randomized controlled trial comparing post-operative bleeding incidence in patients undergoing laser hemorrhoidoplasty (LHP) only versus LHP with hemorrhoidal artery ligation (HAL). Outcome measures included post-operative bleeding and its severity (i.e. verbal rating scale and Clavien-Dindo classification), presence of perianal swelling and pain score (visual analog score) at 1-day, 1-week and 6-weeks post-operatively. Statistical tests were performed and a value of P < 0.05 was considered significant.

Results
Seventy-six patients were randomized. There was no difference in median operating time. The bleeding incidence was highest at 1-week post-operatively (17.1%), and decreased to 1.3% at 6-weeks. There was no significant difference in bleeding incidence between both groups at any of the measured timepoints (P > 0.05). Severity of bleeding and incidence of post-operative perianal swelling were similar in both groups (P > 0.05). There was no difference in median pain scores.

Conclusion
Supplementation of HAL to LHP does not reduce the post-operative bleeding incidence. LHP is sufficient as a stand-alone procedure for treating haemorrhoids.
Trial registration: National Registration Number is NMRR-15-1112-24065 (IIR). The trial start date was 1st January 2015 with the ClinicalTrials.gov identifier and registration number as NCT04667169.