bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of whole-genome promoter nucleosome profiling of maternal plasma cell-free DNA for prenatal noninvasive prediction of fetal macrosomia: a retrospective nested case-control study in mainland China
Authors: Lu Qianwen , Guo Zhiwei , Zhang Jun , Wang Ke , Tian Qi , Liu Siping , Li Kun , Xu Cailing , Li Caimin , Lv Zenglu , Zhang Zhigang , Yang Xuexi , Yang Fang 
Published: September 2022

Abstract
Background
Fetal macrosomia is common occurrence in pregnancy, which is associated with several adverse prognosis both of maternal and neonatal. While, the accuracy of prediction of fetal macrosomia is poor. The aim of this study was to develop a reliable noninvasive prediction classifier of fetal macrosomia.

Methods
A total of 3600 samples of routine noninvasive prenatal testing (NIPT) data at 12+ 0–27+ 6 weeks of gestation, which were subjected to low-coverage whole-genome sequencing of maternal plasma cell-free DNA (cfDNA), were collected from three independent hospitals. We identified set of genes with significant differential coverages by comparing the promoter profiling between macrosomia cases and controls. We selected genes to develop classifier for noninvasive predicting, by using support vector machine (SVM) and logistic regression models, respectively. The performance of each classifier was evaluated by area under the curve (AUC) analysis.

Results
According to the available follow-up results, 162 fetal macrosomia pregnancies and 648 matched controls were included. A total of 1086 genes with significantly differential promoter profiling were found between pregnancies with macrosomia and controls (p < 0.05). With the AUC as a reference，the classifier based on SVM (CMA-A2) had the best performance, with an AUC of 0.8256 (95% CI: 0.7927–0.8586).

Conclusions
Our study provides that assessing the risk of fetal macrosomia by whole-genome promoter nucleosome profiling of maternal plasma cfDNA based on low-coverage next-generation sequencing is feasible.
Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma
Authors: Wendler Julia , Fox Christopher P. , Valk Elke , Steinheber Cora , Fricker Heidi , Isbell Lisa K. , Neumaier Simone , Okosun Jessica , Scherer Florian , Ihorst Gabriele , Cwynarski Kate , Schorb Elisabeth , Illerhaus Gerald 
Published: September 2022

Abstract
Background
Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) is a rare disorder with an increasing incidence over the past decades. High-level evidence has been reported for the MATRix regimen (high-dose methotrexate (HD-MTX), high-dose AraC (HD-AraC), thiotepa and rituximab) followed by high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) supporting this approach to be considered a standard therapy in newly diagnosed PCNSL patients ≤ 70 years. However, early treatment-related toxicities (predominantly infectious complications), occurring in up to 28% per MATRix cycle, diminish its therapeutic success. Furthermore, sensitivity to first-line treatment is an independent prognostic factor for improved overall survival (OS) in PCNSL. Thus, patients achieving early partial remission (PR) after 2 cycles of MATRix might be over-treated with 4 cycles, in the context of consolidation HCT-ASCT.

Methods
This is an open-label, multicentre, randomized phase III trial with two parallel arms. 326 immunocompetent patients with newly diagnosed PCNSL will be recruited from 37 German, 1 Austrian and 12 UK sites. Additional IELSG (International Extranodal Lymphoma Study Group) sites are planned. The objective is to demonstrate superiority of a de-escalated and optimised remission induction treatment strategy, followed by HCT-ASCT. Randomization (1:1) will be performed after completion of all screening procedures. Patients in Arm A (control treatment) will receive 4 cycles of MATRix. Patients in Arm B (experimental treatment) will receive a pre-phase (R/HD-MTX), followed by 2 cycles of MATRix. Patients in both arms achieving PR or better will proceed to HCT-ASCT (BCNU, thiotepa). The primary endpoint of the study is event-free-survival (EFS), defined as time from randomization to premature end of treatment due to any reason, lymphoma progression or death whichever occurs first. Secondary endpoints include OS, progression free survival (PFS), toxicity, neurocognitive impairment and quality of life. Minimal follow-up is 24 months.

Discussion
Current treatment options for PCNSL in patients ≤ 70 years have improved remarkably over recent years. However, the potential efficacy benefits are offset by an increased incidence of short-term toxicities which can impact on treatment delivery and hence on survival outcomes. In patients ≤ 70 years with newly diagnosed PCNSL addressing the need to reduce treatment-related toxicity by de-escalating and optimising the induction phase of treatment, is a potentially attractive treatment strategy.

Trial registration
German clinical trials registry DRKS00022768 registered June 10th, 2021.
Paradoxical downregulation of LPAR3 exerts tumor-promoting activity through autophagy induction in Ras-transformed cells
Authors: Hwang Sung-Hee , Kim Hye-Gyo , Lee Michael 
Published: September 2022

AbstractBackgroundLysophosphatidic acid receptor 3 (LPAR3) is coupled to Gαi/oand Gα11/qsignaling. Previously, we reported thatLPAR3is highly methylated in carcinogen-induced transformed cells. Here, we demonstrate that LPAR3 exhibits malignant transforming activities, despite being downregulated in transformed cells.MethodsThe LPAR3 knockout (KO) in NIH 3 T3 and Bhas 42 cells was established using the CRISPR/Cas9 system. Both RT-PCR and DNA sequencing were performed to confirm the KO of LPAR3. The cellular effects of LPAR3 KO were further examined by WST-1 assay, immunoblotting analysis, transwell migration assay, colony formation assay, wound scratch assday, in vitro cell transformation assay, and autophagy assay.ResultsIn v-H-ras-transformed cells (Ras-NIH 3 T3) with LPAR3 downregulation, ectopic expression of LPAR3 significantly enhanced the migration. In particular, LPAR3 knockout (KO) in Bhas 42 (v-Ha-ras transfected Balb/c 3 T3) and NIH 3 T3 cells caused a decrease in cell survival, transformed foci, and colony formation. LPAR3 KO led to the robust accumulation of LC3-II and autophagosomes and inhibition of autophagic flux by disrupting autophagosome fusion with lysosome. Conversely, autolysosome maturation proceeded normally in Ras-NIH 3 T3 cells upon LPAR3 downregulation. Basal phosphorylation of MEK and ERK markedly increased in Ras-NIH 3 T3 cells, whereas being significantly lower in LPAR3 KO cells, suggesting that increased MEK signaling is involved in autophagosome–lysosome fusion in Ras-NIH 3 T3 cells.ConclusionsParadoxical downregulation of LPAR3 exerts cooperative tumor-promoting activity with MEK activation through autophagy induction in Ras-transformed cells. Our findings have implications for the development of cancer chemotherapeutic approaches.
Machine learning-based improvement of MDS-CBC score brings platelets into the limelight to optimize smear review in the hematology laboratory
Authors: Zhu Jaja , Lemaire Pierre , Mathis Stéphanie , Ronez Emily , Clauser Sylvain , Jondeau Katayoun , Fenaux Pierre , Adès Lionel , Bardet Valérie 
Published: September 2022

Abstract
Background
Myelodysplastic syndromes (MDS) are clonal hematopoietic diseases of the elderly characterized by chronic cytopenias, ineffective and dysplastic haematopoiesis, recurrent genetic abnormalities and increased risk of progression to acute myeloid leukemia. A challenge of routine laboratory Complete Blood Counts (CBC) is to correctly identify MDS patients while simultaneously avoiding excess smear reviews. To optimize smear review, the latest generations of hematology analyzers provide new cell population data (CPD) parameters with an increased ability to screen MDS, among which the previously described MDS-CBC Score, based on Absolute Neutrophil Count (ANC), structural neutrophil dispersion (Ne-WX) and mean corpuscular volume (MCV). Ne-WX is increased in the presence of hypogranulated/degranulated neutrophils, a hallmark of dysplasia in the context of MDS or chronic myelomonocytic leukemia. Ne-WX and MCV are CPD derived from leukocytes and red blood cells, therefore the MDS-CBC score does not include any platelet-derived CPD. We asked whether this score could be improved by adding the immature platelet fraction (IPF), a CPD used as a surrogate marker of dysplastic thrombopoiesis.

Methods
Here, we studied a cohort of more than 500 individuals with cytopenias, including 168 MDS patients. In a first step, we used Breiman’s random forests algorithm, a machine-learning approach, to identify the most relevant parameters for MDS prediction. We then designed Classification And Regression Trees (CART) to evaluate, using resampling, the effect of model tuning parameters on performance and choose the “optimal” model across these parameters.

Results
Using random forests algorithm, we identified Ne-WX and IPF as the strongest discriminatory predictors, explaining 37 and 33% of diagnoses respectively. To obtain “simplified” trees, which could be easily implemented into laboratory middlewares, we designed CART combining MDS-CBC score and IPF. Optimal results were obtained using a MDS-CBC score threshold equal to 0.23, and an IPF threshold equal to 3%.

Conclusions
We propose an extended MDS-CBC score, including CPD from the three myeloid lineages, to improve MDS diagnosis on routine laboratory CBCs and optimize smear reviews.
Is laterality in breast Cancer still worth studying? Local experience in Bahrain
Authors: Al Saad Suhair , Al Shenawi Hamdi , Almarabheh Amer , Al Shenawi Noor , Mohamed Abdulla Ismaeel , Yaghan Rami 
Published: September 2022

Abstract
Background
Laterality in breast cancer means an increased frequency of left-sided breast cancers compared to right-sided breast cancers ranging between 1.05 and 1.26. It was first described in 1935 by Fellenberg, Sweden. The explanation of this phenomenon is not clear, but the association with other factors was found. This study aimed to explore the laterality of breast cancer in Bahrain as a model for Arabian countries. The association of laterality with the clinicopathological characteristics of the tumor was also analyzed to explore any applied clinical value.

Methods
This is a cross-sectional, retrospective review of a particular ethnic population to study laterality of breast cancer versus a number of clinicopathological factors, as well as prognosis. The study analyzed 228 breast cancer patients treated in Arabian Gulf University facilities in Bahrain between 1999 and 2020. Three bilateral breast cancer and two malignant phyllodes patients were excluded.
The following variables were analyzed: laterality ratio (Lt/Rt) and the association between laterality and clinicopathological characteristics (age at diagnosis, family history of malignancy, size of the tumor, tumor grade, histological type, hormonal receptors and HER2, axillary lymph node status, tumor stage, five-year survival rate, nulliparity, and multifocality).

Results
The laterality ratio (Lt/Rt) was 1.06 and was 0.97 for patients below 50 years of age, and 1.19 for patients 50 years of age and above.
Analysis of our data showed a statistically significant association between laterality and tumor stage (p. value =0.025) at presentation, and laterality and family history of malignancy (p. value =0.052).
Right-sided breast cancer was associated with a higher positive family history of malignancy and an increased ratio of locally advanced and metastatic disease, and a reduced 5-year survival in relation to size and stage. Left-sided breast cancer was associated with higher early tumor stage.

Conclusion
This is the first study exploring the issue of breast cancer laterality in a defined Arabian population. The laterality ratio in this study was 1.06, which is consistent with the globally published range (1.05 to 1.26) and is increasing with increasing age.
The association between breast cancer laterality, and the hormonal and HER2 is still not widely addressed in the available literature, although other clinicopathological characteristics were extensively analyzed.
The effects of topical cycloplegics in acute acquired comitant esotropia induced by excessive digital device usage
Authors: Hayashi Rijo , Hayashi Shimmin , Machida Shigeki 
Published: September 2022

Abstract
Background
Acute acquired comitant esotropia induced by excessive digital device usage, especially smartphones (SAACE), has been increasing over the past few years. One suggested mechanism is convergence spasm induced by excessive near work, with refraining from digital device use considered to be an effective method for decreasing the degree of esodeviation. However, if symptoms persist and are untreated over time, recovery becomes more difficult. The present study evaluated the effects of topical cycloplegics on persistent SAACE untreated for over 1 year.

Methods
Patients with sustained SAACE that was untreated for over 1 year were evaluated. Digital device usage was discouraged and a topical cycloplegic, 0.4% tropicamide, was prescribed at bedtime. After obtaining informed consent, the 14 out of 23 enrolled patients who agreed to eye drop administration were defined as the study group, with the others serving as the controls. After a 3-month follow-up, patients who elected to undergo surgery were analyzed as the surgery group. Changes in esotropia angles, stereoacuity and diplopia complaints were evaluated after a 3-month follow-up.

Results
Esotropia angles decreased and stereoacuity improved after a 3-month treatment in the study group (P < 0.01). Diplopia disappeared in 13 patients (92.9%, totally disappeared or disappeared when using glasses with built-in prisms). Among 11 patients with untreated esotropia ranging from 1–3 years, decreases in esotropia angles were correlated to untreated esotropia duration (near: R = -0.6; distance: R = 0.7; both P < 0.05). Esotropia angles in the control group exhibited a tendency to increase while stereoacuity tended to deteriorate after the 3-month follow-up. As diplopia did not disappear in any patients, 7 elected to undergo surgery and were enrolled as the surgery group. While esotropia angles decreased in the study group, they were lower than the surgery group (P < 0.01), but higher than the control group (P < 0.01). Stereoacuity was worse in the control versus the study and surgery groups (both P < 0.05).

Conclusion
Results suggest short-acting topical cycloplegics are effective in SAACE patients with long untreated periods. Decreases in esotropia angles were negatively correlated to untreated esotropia duration, which suggests the necessity of early treatment.
Latent classes of posttraumatic stress disorder among survivors of the Bam Earthquake after 17 years
Authors: Abolhadi Elham , Divsalar Parisa , Mosleh-Shirazi Mohammad Amin , Dehesh Tania 
Published: September 2022

Abstract
Background
The purpose of this study was to identify latent classes of the severity of post-traumatic stress disorder (PTSD) among the survivors of the earthquake in Bam, south-eastern Iran, 17 years after the disaster. The most influential predictor variables of PTSD classes were also investigated.

Methods
Eight hundred survivors of the Bam earthquake who were at least four years old in that disaster were selected by multistage sampling. The PTSD Checklist-Civilian Version was used. Latent class analysis was performed to identify subgroups of people with different PTSD symptom profiles. Latent class regression analysis was used to explore the influence of demographic and traumatic variables on each class membership.

Results
We found three latent classes of PTSD, with the following profiles emerging: Low Symptom (56.6% of the participants), Moderate Symptom (23.5%), and Severe Symptom (19.9%). Old age [OR = 2.20, 95% CI = (1.46, 3.32)], physical injury [OR = 1.95, 95% CI = (1.24, 3.06)], being trapped under the rubble [OR = 1.81, 95% CI = (1.15, 2.86)], and death of a family member [OR = 1.86, 95% CI = (1.12, 3.09)] were positive risk factors for PTSD and increased the chance of being in classes having more severe symptoms. Having a high educational level was a negative risk factor [OR = 0.86, 95% CI = (0.67, 1.11)].

Conclusions
The severity of PTSD 17 years after the earthquake shows that natural disasters such as earthquakes have long-term consequences, and earthquake survivors must have psychological support and long term health care.
After any catastrophic earthquake, governments should establish psychology and psychotherapy centers for earthquake victims, and these centers should support earthquake victims for a sufficiently long time.
Feeding, caregiving practices, and developmental delay among children under five in lowland Nepal: a community-based cross-sectional survey
Authors: Dulal Sophiya , Prost Audrey , Karki Surendra , Merom Dafna , Shrestha Bhim Prasad , Bhandari Bishnu , Manandhar Dharma S. , Osrin David , Costello Anthony , Saville Naomi M. 
Published: September 2022

AbstractBackgroundNurturing care, including adequate nutrition, responsive caregiving and early learning, is critical to early childhood development. In Nepal, national surveys highlight inequity in feeding and caregiving practices for young children. Our objective was to describe infant and young child feeding (IYCF) and cognitive and socio-emotional caregiving practices among caregivers of children under five in Dhanusha district, Nepal, and to explore socio-demographic and economic factors associated with these practices.MethodsWe did a cross-sectional analysis of a subset of data from the MIRA Dhanusha cluster randomised controlled trial, including mother-child dyads (N = 1360), sampled when children were median age 46 days and a follow-up survey of the same mother-child dyads (N = 1352) when children were median age 38 months. We used World Health Organization IYCF indicators and questions from the Multiple Indicator Cluster Survey-4 tool to obtain information on IYCF and cognitive and socio-emotional caregiving practices. Using multivariable logistic regression models, potential explanatory household, parental and child-level variables were tested to determine their independent associations with IYCF and caregiving indicators.ResultsThe prevalence of feeding indicators varied. IYCF indicators, including ever breastfed (99%), exclusive breastfeeding (24-hour recall) (89%), and vegetable/fruit consumption (69%) were common. Problem areas were early initiation of breastfeeding (16%), colostrum feeding (67%), no pre-lacteal feeding (53%), timely introduction of complementary feeding (56%), minimum dietary diversity (49%) and animal-source food consumption (23%). Amongst caregiving indicators, access to 3+ children’s books (7%), early stimulation and responsive caregiving (11%), and participation in early childhood education (27%) were of particular concern, while 64% had access to 2+ toys and 71% received adequate care. According to the Early Child Development Index score, only 38% of children were developmentally on track. Younger children from poor households, whose mothers were young, had not received antenatal visits and delivered at home were at higher risk of poor IYCF and caregiving practices.ConclusionsSuboptimal caregiving practices, inappropriate early breastfeeding practices, delayed introduction of complementary foods, inadequate dietary diversity and low animal-source food consumption are challenges in lowland Nepal. We call for urgent integrated nutrition and caregiving interventions, especially as interventions for child development are lacking in Nepal.
A qualitative exploration of Ugandan mental health care workers’ perspectives and experiences on sexual and reproductive health of people living with mental illness in Uganda
Authors: Tumwakire Emily , Arnd Hofmeister , Gavamukulya Yahaya 
Published: September 2022

Abstract
Background
People with Mental Illness experience vast sexual and reproductive health challenges due to the affected mental health. Globally, prevalence of mental illness is on the rise with subsequent increase in the number of people with sexual and reproductive challenges warranting urgent public health intervention. However, information on the perceptions and experiences of mental health workers, the key health care providers for this population is generally lacking yet it’s essential for formulation of appropriate policies and public health interventions.

Aim
To explore Ugandan mental health care worker’s perspectives and experiences on the sexual and reproductive health of people living with mental illness in Uganda in order to generate recommendations to the ministry of health on how it can be improved.

Materials and methods
Qualitative study design was employed with utilization of phone call semi-structured in-depth interviews to collect data from 14 mental health workers from Uganda’s National mental referral hospital, Butabika. Purposive sampling and convenience recruitment was done and the collected data was analyzed using Thematic content analysis.

Results
Four themes were generated which included people with Mental illness having normal sexual needs, mental illness effect on sexuality and relationships, practices for safeguarding sexuality of people with mental illness and the barriers encountered in the provision of sexual and reproductive health services at a mental hospital.

Conclusion
People with mental illness experience a multitude of sexual and reproductive health challenges that need public health interventions. However, the integration of sexual and reproductive health services in a mental hospital are not yet successful making people with mental illness to remain with unaddressed health challenges. Policies should therefore be developed and implemented to ensure successful integration of sexual and reproductive health at all mental health service care provision points.
The feasibility of collecting the physiotherapy outcomes airway clearance, physical activity and fitness for the Australian Cystic Fibrosis Data Registry
Authors: Potter Angela , Singh Ben , Scutter Emily , Maher Carol 
Published: September 2022

Abstract
Background
Physiotherapy-related data, such as airway clearance techniques (ACTS), physical activity and aerobic fitness are not consistently included in international cystic fibrosis (CF) data registries. This study aimed to pilot the collection of ACTS, physical activity and fitness in a hospital CF clinic, as a step towards informing future national implementation.

Methods
This study was undertaken in a CF clinic within a major tertiary hospital. Patients and families were invited to participate. Participants completed self-report questionnaires on ACT use and those aged ≥ 10 years completed a physical activity questionnaire (Core Indicators and Measures of Youth Health Survey) and aerobic fitness test (the A-STEP test). Participants also completed a survey to explore the tolerance and acceptability of the fitness test, and the perceived accuracy of the self-reported data collection.

Results
Forty patients agreed to participate in the study (mean age = 9.8, SD = 4.1 years old; 52.5% female). All patients and/or families that were approached agreed to participate and completion rate for the ACTs and physical activity surveys was 98% and 100% (respectively). Completion rate for the fitness test was 55%, due to time constraints. Most participants agreed (≥ 90%) they could accurately provide ACT and physical activity data, and the assessments were tolerable and acceptable.

Conclusions
Patients with CF and their families are able to and can acceptably provide physiotherapy-related data, and collecting self-report ACTs and physical activity data is highly feasibly during routine CF clinic visits. However, aerobic fitness testing using the A-STEP test may be less feasible in clinic environments, due to time constraints.