bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic outcome of ‘type 2 diabetes mellitus and breast cancer’ association pivots on hypoxia-hyperglycemia axis
Authors: Durrani Ilhaam Ayaz , Bhatti Attya , John Peter 
Published: July 2021

AbstractType 2 diabetes mellitus and breast cancer are complex, chronic, heterogeneous, and multi-factorial diseases; with common risk factors including but not limited to diet, obesity, and age. They also share mutually inclusive phenotypic features such as the metabolic deregulations resulting from hyperglycemia, hypoxic conditions and hormonal imbalances. Although, the association between diabetes and cancer has long been speculated; however, the exact molecular nature of this link remains to be fully elucidated. Both the diseases are leading causes of death worldwide and a causal relationship between the two if not addressed, may translate into a major global health concern. Previous studies have hypothesized hyperglycemia, hyperinsulinemia, hormonal imbalances and chronic inflammation, as some of the possible grounds for explaining how diabetes may lead to cancer initiation, yet further research still needs to be done to validate these proposed mechanisms. At the crux of this dilemma, hyperglycemia and hypoxia are two intimately related states involving an intricate level of crosstalk and hypoxia inducible factor 1, at the center of this, plays a key role in mediating an aggressive disease state, particularly in solid tumors such as breast cancer. Subsequently, elucidating the role of HIF1 in establishing the diabetes-breast cancer link on hypoxia-hyperglycemia axis may not only provide an insight into the molecular mechanisms underlying the association but also, illuminate on the prognostic outcome of the therapeutic targeting of HIF1 signaling in diabetic patients with breast cancer or vice versa. Hence, this review highlights the critical role of HIF1 signaling in patients with both T2DM and breast cancer, potentiates its significance as a prognostic marker in comorbid patients, and further discusses the potential prognostic outcome of targeting HIF1, subsequently establishing the pressing need for HIF1 molecular profiling-based patient selection leading to more effective therapeutic strategies emerging from personalized medicine.
Derivation and validation of a lipid-covered prognostic model for mature T-cell lymphomas
Authors: Lu Tiange , Shi Lei , Shi Guanggang , Cai Yiqing , Hu Shunfeng , Liu Jiarui , Ren Shuai , Zhou Xiangxiang , Wang Xin 
Published: July 2021

Abstract
Background
Mature T-cell lymphomas (MTCLs), a group of diseases with high aggressiveness and vulnerable prognosis, lack for the accurate prognostic stratification systems at present. Novel prognostic markers and models are urgently demanded. Aberrant lipid metabolism is closely related to the tumor progression but its prognostic significance in MTCLs remains unexplored. This study aims to investigate the relationship between dysregulated lipid metabolism and survival prognosis of MTCLs and establish a novel and well-performed prognostic scoring system for MTCL patients.

Methods
A total of 173 treatment-naive patients were enrolled in this study. Univariate and multivariate Cox regression analysis were performed to assess the prognostic significance of serum lipid profiles and screen out independent prognostic factors, which constituted a novel prognostic model for MTCLs. The performance of the novel model was assessed in the training and validation cohort, respectively, by examining its calibration, discrimination and clinical utility.

Results
Among the 173 included patients, 115 patients (01/2006–12/2016) constituted the training cohort and 58 patients (01/2017–06/2020) formed the validation cohort. Univariate analysis revealed declined total cholesterol (TC, P = 0.000), high-density lipoprotein cholesterol (HDL-C, P = 0.000) and increased triglycerides (TG, P = 0.000) correlated to inferior survival outcomes. Multivariate analysis revealed extranodal involved sites ≥ 2 (hazard ratio [HR]: 2.439; P = 0.036), β2-MG ≥ 3 mg/L (HR: 4.165; P = 0.003) and TC < 3.58 mmol/L (HR: 3.338; P = 0.000) were independent predictors. Subsequently, a novel prognostic model, EnBC score, was constructed with these three factors. Harrell’s C-index of the model in the training and validation cohort was 0.840 (95% CI 0.810–0.870) and 0.882 (95% CI 0.822–0.942), respectively, with well-fitted calibration curves. The model divided patients into four risk groups with distinct OS [median OS: not available (NA) vs. NA vs. 14.0 vs. 4.0 months, P < 0.0001] and PFS (median PFS: 84.0 vs. 19.0 vs. 8.0 vs. 1.5 months, P < 0.0001). Time-dependent receiver operating characteristic curve and decision curve analysis further revealed that EnBC score provided higher diagnostic capacity and clinical benefit, compared with International Prognostic Index (IPI).

Conclusion
Firstly, abnormal serum lipid metabolism was demonstrated significantly related to the survival of MTCL patients. Furthermore, a lipid-covered prognostic scoring system was established and performed well in stratifying patients with MTCLs.
Malaria prevalence and long-lasting insecticidal net use in rural western Uganda: results of a cross-sectional survey conducted in an area of highly variable malaria transmission intensity
Authors: Cote Claire M. , Goel Varun , Muhindo Rabbison , Baguma Emmanuel , Ntaro Moses , Shook-Sa Bonnie E. , Reyes Raquel , Staedke Sarah G. , Mulogo Edgar M. , Boyce Ross M. 
Published: July 2021

Abstract
Background
Long-lasting insecticidal nets (LLINs) remain a cornerstone of malaria control, but strategies to sustain universal coverage and high rates of use are not well-defined. A more complete understanding of context-specific factors, including transmission intensity and access to health facilities, may inform sub-district distribution approaches and tailored messaging campaigns.

Methods
A cross-sectional survey of 2190 households was conducted in a single sub-county of western Uganda that experiences highly variable malaria transmission intensity. The survey was carried out approximately 3 years after the most recent mass distribution campaign. At each household, study staff documented reported LLIN use and source among children 2 to 10 years of age and performed a malaria rapid diagnostic test. Elevation and distance to the nearest health facility was estimated for each household. Associations between parasite prevalence and LLIN use were estimated from log binomial regression models with elevation and distance to clinic being the primary variables of interest.

Results
Overall, 6.8% (148 of 2170) of children age 2–10 years of age had a positive RDT result, yielding a weighted estimate of 5.8% (95% confidence interval [CI] 5.4–6.2%). There was substantial variability in the positivity rates among villages, with the highest elevation villages having lower prevalence than lowest-elevation villages (p < .001). Only 64.7% (95% CI 64.0–65.5%) of children were reported to have slept under a LLIN the previous night. Compared to those living < 1 km from a health centre, households at ≥ 2 km were less likely to report the child sleeping under a LLIN (RR 0.86, 95% CI 0.83–0.89, p < .001). Households located farther from a health centre received a higher proportion of LLINs from government distributions compared to households living closer to health centres.

Conclusions
LLIN use and sourcing was correlated with household elevation and estimated distance to the nearest health facility. The findings suggest that current facility-based distribution strategies are limited in their reach. More frequent mass distribution campaigns and complementary approaches are likely required to maintain universal LLIN coverage and high rates of use among children in rural Uganda.
Portable HEPA filter air cleaner use during pregnancy and children’s behavior problem scores: a secondary analysis of the UGAAR randomized controlled trial
Authors: Enkhbat Undarmaa , Gombojav Enkhjargal , Banzrai Chimeglkham , Batsukh Sarangerel , Boldbaatar Buyantushig , Enkhtuya Enkhtuul , Ochir Chimedsuren , Bellinger David C. , Lanphear Bruce P. , McCandless Lawrence C. , Allen Ryan W. 
Published: July 2021

Abstract
Background
Developmental exposure to particulate matter (PM) air pollution may impair children’s behaviors. Our objectives were to quantify the impact of reducing indoor PM using portable HEPA filter air cleaners during pregnancy on behavioral problems in children and to assess associations between indoor fine PM (PM2.5) concentrations during pregnancy and children’s behavior.

Methods
This is a secondary analysis of a single-blind parallel-group randomized controlled trial in which we randomly assigned 540 non-smoking pregnant women to receive 1 or 2 HEPA filter air cleaners or no air cleaners. We administered the Behavior Assessment System for Children (BASC-3) to caregivers when children were a mean age of 23 months, and again at a mean age of 48 months. Primary outcomes were the four BASC-3 composite scales: externalizing problems, internalizing problems, adaptive skills, and the behavioral symptoms index. We imputed missing data using multiple imputation with chained equations. The primary analysis was by intention-to-treat. In a secondary analysis, we evaluated associations between BASC-3 composite indices and modeled trimester-specific PM2.5 concentrations inside residences.

Results
We enrolled participants at a median of 11 weeks gestation. After excluding miscarriages, still births and neonatal deaths, our analysis included 478 children (233 control and 245 intervention). We observed no differences in the mean BASC-3 scores between treatment groups. An interquartile increase (20.1 µg/m3) in first trimester PM2.5 concentration was associated with higher externalizing problem scores (2.4 units, 95% CI: 0.7, 4.1), higher internalizing problem scores (2.4 units, 95% CI: 0.7, 4.0), lower adaptive skills scores (-1.5 units, 95% CI: -3.0, 0.0), and higher behavior symptoms index scores (2.3 units, 95% CI: 0.7, 3.9). Third trimester PM2.5 concentrations were also associated with some behavioral indices at age 4, but effect estimates were smaller. No significant associations were observed with PM2.5 concentrations during the second trimester or for any of the BASC indices when children were 2 years old.

Conclusion
We found no benefit of reducing indoor particulate air pollution during pregnancy on parent-reported behaviors in children. Associations between indoor PM2.5 concentrations in the first trimester and behavioral scores among 4-year old children suggest that it may be necessary to intervene early in pregnancy to protect children, but these exploratory findings should be interpreted cautiously.

Trial registration
ClinicalTrials.gov: NCT01741051
Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance
Authors: Jiang Weixi , Su Lei , Ao Meng , Guo Xun , Cheng Chen , Luo Yuanli , Xie Zhuoyan , Wang Xingyue , Wang Junrui , Liu Shuling , Cao Yang , Li Pan , Wang Zhigang , Ran Haitao , Zhou Zhiyi , Ren Jianli 
Published: July 2021

Abstract
Background
Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents.

Results
In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors.

Conclusion
This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel.

Graphic Abstract
Community-based surveillance in internally displaced people’s camps and urban settings during a complex emergency in Yemen in 2020
Authors: Baaees Manal Salem Omar , Naiene Jeremias D. , Al-Waleedi Ali Ahmed , Bin-Azoon Nasreen Salem , Khan Muhammad Fawad , Mahmoud Nuha , Musani Altaf 
Published: July 2021

Abstract
Background
The need for early identification of coronavirus disease (COVID-19) cases in communities was high in Yemen during the first wave of the COVID-19 epidemic because most cases presenting to health facilities were severe. Early detection of cases would allow early interventions to interrupt the transmission chains. This study aimed to describe the implementation of community-based surveillance (CBS) in in internally displaced people (IDP) camps and urban settings in Yemen from 15 April 2020 to 30 September 2020.

Methods
Following the Centers for Disease Control and Prevention guidance for evaluation of surveillance systems, we assessed the usefulness and acceptability of CBS. For acceptability, we calculated the proportion of trained volunteers who reported disease alerts. To assess the usefulness, we compared the alerts reported through the electronic diseases early warning system (eDEWS) with the alerts reported through CBS and described the response activities implemented.

Results
In Al-Mukalla City, 18% (14/78) of the volunteers reported at least one alert. In IDP camps, 58% (18/31) of volunteers reported at least one alert. In Al-Mukalla City, CBS detected 49 alerts of influenza-like illness, whereas health facilities detected 561 cases of COVID-19. In IDP camps, CBS detected 91 alerts of influenza-like illness, compared to 10 alerts detected through eDEWS. In IDP camps, CBS detected three other syndromes besides influenza-like illness (febrile illness outbreak suspicion, acute diarrhoea, and skin disease). In IDP camps, public health actions were implemented for each disease detected and no further cases were reported.

Conclusions
In Yemen, CBS was useful for detecting suspected outbreaks in IDP camps. CBS implementation did not yield expected results in general communities in urban areas in the early stage of the COVID-19 pandemic when little was known about the disease. In the urban setting, the system failed to detect suspected COVID-19 cases and other diseases despite the ongoing outbreaks reported through eDEWS. In Yemen, as in other countries, feasibility and acceptability studies should be conducted few months before CBS expansion in urban communities. The project should be expanded in IDP camps, by creating COVID-19 and other disease outbreak reporting sites.
Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation
Authors: Barile Melania , Imaz-Rosshandler Ivan , Inzani Isabella , Ghazanfar Shila , Nichols Jennifer , Marioni John C. , Guibentif Carolina , Göttgens Berthold 
Published: July 2021

Abstract
Background
Single-cell technologies are transforming biomedical research, including the recent demonstration that unspliced pre-mRNA present in single-cell RNA-Seq permits prediction of future expression states. Here we apply this RNA velocity concept to an extended timecourse dataset covering mouse gastrulation and early organogenesis.

Results
Intriguingly, RNA velocity correctly identifies epiblast cells as the starting point, but several trajectory predictions at later stages are inconsistent with both real-time ordering and existing knowledge. The most striking discrepancy concerns red blood cell maturation, with velocity-inferred trajectories opposing the true differentiation path. Investigating the underlying causes reveals a group of genes with a coordinated step-change in transcription, thus violating the assumptions behind current velocity analysis suites, which do not accommodate time-dependent changes in expression dynamics. Using scRNA-Seq analysis of chimeric mouse embryos lacking the major erythroid regulator Gata1, we show that genes with the step-changes in expression dynamics during erythroid differentiation fail to be upregulated in the mutant cells, thus underscoring the coordination of modulating transcription rate along a differentiation trajectory. In addition to the expected block in erythroid maturation, the Gata1-chimera dataset reveals induction of PU.1 and expansion of megakaryocyte progenitors. Finally, we show that erythropoiesis in human fetal liver is similarly characterized by a coordinated step-change in gene expression.

Conclusions
By identifying a limitation of the current velocity framework coupled with in vivo analysis of mutant cells, we reveal a coordinated step-change in gene expression kinetics during erythropoiesis, with likely implications for many other differentiation processes.
MRI-based radiomics models to assess prostate cancer, extracapsular extension and positive surgical margins
Authors: He Dong , Wang Ximing , Fu Chenchao , Wei Xuedong , Bao Jie , Ji Xuefu , Bai Honglin , Xia Wei , Gao Xin , Huang Yuhua , Hou Jianquan 
Published: July 2021

Abstract
Purpose
To investigate the performance of magnetic resonance imaging (MRI)-based radiomics models for benign and malignant prostate lesion discrimination and extracapsular extension (ECE) and positive surgical margins (PSM) prediction.

Methods and materials
In total, 459 patients who underwent multiparametric MRI (mpMRI) before prostate biopsy were included. Radiomic features were extracted from both T2-weighted imaging (T2WI) and the apparent diffusion coefficient (ADC). Patients were divided into different training sets and testing sets for different targets according to a ratio of 7:3. Radiomics signatures were built using radiomic features on the training set, and integrated models were built by adding clinical characteristics. The areas under the receiver operating characteristic curves (AUCs) were calculated to assess the classification performance on the testing sets.

Results
The radiomics signatures for benign and malignant lesion discrimination achieved AUCs of 0.775 (T2WI), 0.863 (ADC) and 0.855 (ADC + T2WI). The corresponding integrated models improved the AUC to 0.851/0.912/0.905, respectively. The radiomics signatures for ECE achieved the highest AUC of 0.625 (ADC), and the corresponding integrated model achieved the highest AUC (0.728). The radiomics signatures for PSM prediction achieved AUCs of 0.614 (T2WI) and 0.733 (ADC). The corresponding integrated models reached AUCs of 0.680 and 0.766, respectively.

Conclusions
The MRI-based radiomics models, which took advantage of radiomic features on ADC and T2WI scans, showed good performance in discriminating benign and malignant prostate lesions and predicting ECE and PSM. Combining radiomics signatures and clinical factors enhanced the performance of the models, which may contribute to clinical diagnosis and treatment.
Presence of dogs and proximity to a wildlife reserve increase household level risk of tungiasis in Kwale, Kenya
Authors: Larson Peter S , Ono Masanobu , Changoma Mwatasa , Goto Kensuke , Kaneko Satoshi , Moji Kazuhiko , Minakawa Noboru 
Published: July 2021

Abstract
Introduction
Tungiasis is a ectopic skin disease caused by some species of fleas in the Tunga genus, most notably T. penetrans. The disease afflicts poor and marginalized communities in developing countries. Transmission of tungiasis comprises a complex web of factors including domesticated animals and wildlife. This research explores animal and environmental risk factors for tungiasis in an area adjacent to a wildlife reserve in Kwale, Kenya.

Methods
A two-stage complex sampling strategy was used. Households were selected from three areas in and around Kwale Town, Kenya, an area close to the Kenyan Coast. Households were listed as positive if at least one member had tungiasis. Each household was administered a questionnaire regarding tungiasis behaviors, domesticated animal assets, and wild animal species that frequent the peridomiciliary area. Associations of household tungiasis were tests with household and environmental variables using regression methods.

Results
The study included 319 households. Of these, 41 (12.85%) were found to have at least one person who had signs of tungiasis. There were 295 (92.48%) households that possessed at least one species of domesticated animal. It was reported that wildlife regularly come into the vicinity of the home 90.59% of households. Presence of dogs around the home (OR 3.85; 95% CI 1.84; 8.11) and proximity to the park were associated with increased risk for tungiasis infestation in humans in a multivariate regression model.

Conclusions
Human tungiasis is a complex disease associated with domesticated and wild animals. Canines in particular appear to be important determinants of household level risk.
Can politically oriented interventions in built heritage contribute to its authenticity? Erbil Citadel’s Babylonian Gate as a case study
Authors: Jasim Mohammed Awadh , Hanks Laura , Borsi Katharina 
Published: July 2021

AbstractToday, the concept of built heritage authenticity is aprojection screen for conflicting demandsand thus a ‘contested field’. Short-sighted readings started to drag the concept behind different ill-considered treatises, in which some heritage aspects loosely outweighed other aspects. Archaeological perspectives that tend to freeze heritage structures in time, such as those that are privileged upon other contemporary socio-cultural issues, while political takes also overshadowed other epistemological prospects, and vice versa. Repercussions have made inclusion of what is regarded as ‘inevitable changes’ within the built context problematic as to the re-interpretation and thus assessment of its authenticity. Despite their possible momentary threat to the latter, these changes may add to the cultural value of the context over time, granting new potential that may instead boost its authenticity. This paper investigates the potential continuity of Erbil Citadel’s Babylonian Gate as an inevitable change within the site’s built context by studying the Gate’s controversial political impacts on the context’s authenticity. This study affirms that authenticity is a transcendental value of an open-ended progressive nature, which cannot be reduced to a specific period or properties within the historical chronology of built heritage. Hence, authenticity should be approached as a meaningful existential issue, while revelation of its essence and thus its dimension entails precise scrutiny of both the tangibles and intangibles of the context. However, to be part of its authenticity, any change in the context should be adaptable and possibly incorporated as a new value within its cultural strata, thus enabling progressive support for site authenticity.