bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional generative adversarial network driven radiomic prediction of mutation status based on magnetic resonance imaging of breast cancer
Authors: Huang Zi Huai , Chen Lianghong , Sun Yan , Liu Qian , Hu Pingzhao 
Published: March 2024

Abstract
Background
Breast Cancer (BC) is a highly heterogeneous and complex disease. Personalized treatment options require the integration of multi-omic data and consideration of phenotypic variability. Radiogenomics aims to merge medical images with genomic measurements but encounter challenges due to unpaired data consisting of imaging, genomic, or clinical outcome data. In this study, we propose the utilization of a well-trained conditional generative adversarial network (cGAN) to address the unpaired data issue in radiogenomic analysis of BC. The generated images will then be used to predict the mutations status of key driver genes and BC subtypes.

Methods
We integrated the paired MRI and multi-omic (mRNA gene expression, DNA methylation, and copy number variation) profiles of 61 BC patients from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). To facilitate this integration, we employed a Bayesian Tensor Factorization approach to factorize the multi-omic data into 17 latent features. Subsequently, a cGAN model was trained based on the matched side-view patient MRIs and their corresponding latent features to predict MRIs for BC patients who lack MRIs. Model performance was evaluated by calculating the distance between real and generated images using the Fréchet Inception Distance (FID) metric. BC subtype and mutation status of driver genes were obtained from the cBioPortal platform, where 3 genes were selected based on the number of mutated patients. A convolutional neural network (CNN) was constructed and trained using the generated MRIs for mutation status prediction. Receiver operating characteristic area under curve (ROC-AUC) and precision-recall area under curve (PR-AUC) were used to evaluate the performance of the CNN models for mutation status prediction. Precision, recall and F1 score were used to evaluate the performance of the CNN model in subtype classification.

Results
The FID of the images from the well-trained cGAN model based on the test set is 1.31. The CNN for TP53, PIK3CA, and CDH1 mutation prediction yielded ROC-AUC values 0.9508, 0.7515, and 0.8136 and PR-AUC are 0.9009, 0.7184, and 0.5007, respectively for the three genes. Multi-class subtype prediction achieved precision, recall and F1 scores of 0.8444, 0.8435 and 0.8336 respectively. The source code and related data implemented the algorithms can be found in the project GitHub at https://github.com/mattthuang/BC_RadiogenomicGAN.

Conclusion
Our study establishes cGAN as a viable tool for generating synthetic BC MRIs for mutation status prediction and subtype classification to better characterize the heterogeneity of BC in patients. The synthetic images also have the potential to significantly augment existing MRI data and circumvent issues surrounding data sharing and patient privacy for future BC machine learning studies.
Th17/1 and ex-Th17 cells are detected in patients with polyarticular juvenile arthritis and increase following treatment
Authors: Wood Stephanie , Branch Justin , Vasquez Priscilla , DeGuzman Marietta M. , Brown Amanda , Sagcal-Gironella Anna Carmela , Singla Saimun , Ramirez Andrea , Vogel Tiphanie P. 
Published: March 2024

Abstract
Background
A better understanding of the pathogenesis of polyarticular juvenile idiopathic arthritis (polyJIA) is needed to aide in the development of data-driven approaches to guide selection between therapeutic options. One inflammatory pathway of interest is JAK-STAT signaling. STAT3 is a transcription factor critical to the differentiation of inflammatory T helper 17 cells (Th17s). Previous studies have demonstrated increased STAT3 activation in adult patients with rheumatoid arthritis, but less is known about STAT3 activation in polyJIA. We hypothesized that Th17 cells and STAT3 activation would be increased in treatment-naïve polyJIA patients compared to pediatric controls.

Methods
Blood from 17 patients with polyJIA was collected at initial diagnosis and again if remission was achieved (post-treatment). Pediatric healthy controls were also collected. Peripheral blood mononuclear cells were isolated and CD4 + T cell subsets and STAT activation (phosphorylation) were evaluated using flow cytometry. Data were analyzed using Mann–Whitney U and Wilcoxon matched-pairs signed rank tests.

Results
Treatment-naïve polyJIA patients had increased Th17 cells (CD3 + CD4 + interleukin(IL)-17 +) compared to controls (0.15% v 0.44%, p < 0.05), but Tregs (CD3 + CD4 + CD25 + FOXP3 +) from patients did not differ from controls. Changes in STAT3 phosphorylation in CD4 + T cells following ex vivo stimulation were not significantly different in patients compared to controls. We identified dual IL-17 + and interferon (IFN)γ + expressing CD4 + T cells in patients, but not controls. Further, both Th17/1 s (CCR6 + CD161 + IFNγ + IL-17 +) and ex-Th17s (CCR6 + CD161 + IFNγ + IL-17neg) were increased in patients’ post-treatment (Th17/1: 0.3% v 0.07%, p < 0.05 and ex-Th17s: 2.3% v 1.4%, p < 0.05). The patients with the highest IL-17 expressing cells post-treatment remained therapy-bound.

Conclusions
Patients with polyJIA have increased baseline Th17 cells, potentially reflecting higher tonic STAT3 activation in vivo. These quantifiable immune markers may identify patients that would benefit upfront from pathway-focused biologic therapies. Our data also suggest that inflammatory CD4 + T cell subsets not detected in controls but increased in post-treatment samples should be further evaluated as a tool to stratify patients in remission on medication. Future work will explore these proposed diagnostic and prognostic biomarkers.
Effects of the powerball® system on muscle strength, coordination, fatigue, functionality and quality of life in people with multiple sclerosis. A randomized clinical trial
Authors: Blázquez-Fernández Aitor , López-Hazas-Jiménez Gemma , Fernández-Vázquez Diego , Navarro-López Víctor , Fernández-González Pilar , Marcos-Antón Selena , Molina-Rueda Francisco , Cano-de-la-Cuerda Roberto 
Published: March 2024

Abstract
Introduction
Although clinical and functional impairments in the lower limbs have been extensively studied in patients with MS, the upper limb (UL) are also frequently affected. Clinical impairment of the UL in patients with MS is very common with muscle strength and hand dexterity as critical factors in maintaining functional activities that are the basis for independence and quality of life in people with MS.

Objective
To investigate the effects of a training protocol using the Powerball® system in combination with conventional physiotherapy on muscle strength, coordination, fatigue, functionality, and quality of life in persons with MS over an 8-week period.

Materials and methods
A double-blind randomized controlled trial was conducted. The control group received conventional treatment, while the experimental group received additional UL training using the Powerball® system. Both groups received the same number of sessions and weeks of intervention. The following outcome measures were used: isometric grip and pinch strength, Box and Block Test (BBT), Nine Hole Peg Test (NHPT), Abilhand scale, Fatigue Severity Scale (FSS), Multiple Sclerosis Impact Scale (MSIS-29), and Likert satisfaction questionnaire for the experimental group. All measures were administered at baseline, after the treatment, and during a 3-week follow-up period.

Results
25 patients completed the study (12 in the experimental and 13 in the control group). The experimental group showed significant improvements in coordination and manual dexterity of the more affected UL as measured by the BBT comparing pre- to post-treatment (p = 0.048) and pre-treatment to follow-up (p = 0.001), and on the less affected UP comparing pre-treatment to follow-up (p < 0.001) and post-treatment to follow-up (p = 0.034). The Likert-type satisfaction questionnaire obtained a mean score of 89.10 (± 8.54) out of 100 points.

Conclusions
Upper limb treatment protocol using the Powerball® system, in combination with conventional physiotherapy for 8 weeks resulted in significant improvements in the intra-group analysis for UL coordination and manual dexterity in favor of the experimental group. The experimental group showed excellent satisfaction to the treatment.
PKM2 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating epithelial-mesenchymal transition: an experimental research
Authors: Zhou Xin , Li Yanshi , Pan Min , Lu Tao , Liu Chuan , Wang Zhihai , Tang Fengxiang , Hu Guohua 
Published: March 2024

Abstract
Background
Patients with hypopharyngeal carcinoma (HPC) have a poor prognosis mainly because of lymphatic metastasis. This research aimed to determine the PKM2 role in lymphatic metastasis in HPC and the underlying molecular mechanism contributing to this phenomenon.

Methods
PKM2 in HPC was studied for its expression and its likelihood of overall survival using TCGA dataset. Western blotting, qRT-PCR, and IHC were employed to confirm PKM2 expression. Methods including gain- and loss-of-function were used to examine the PKM2 role in HPC metastasis in vitro and in vivo. In vitro and in vivo studies also confirmed lymphatic metastasis’s mechanism.

Results
Prominent PKM2 overexpression was seen in patients with lymphatic metastasis of HPC, and there was an inherent relationship between a high PKM2 level and poor prognosis. In vitro research showed that knocking down PKM2 decreased tumor cell invasion, migration, and proliferation while promoting apoptosis and inhibiting epithelial-mesenchymal transition, but overexpressing PKM2 had the reverse effect. Animal studies suggested that PKM2 may facilitate tumor development and lymphatic metastasis.

Conclusions
Our findings suggest that PKM2 may be a tumor’s promoter gene of lymphatic metastasis, which may promote lymphatic metastasis of HPC by regulating epithelial-mesenchymal transition. PKM2 may be a biomarker of metastatic potential, ultimately providing a basis for exploring new therapeutic targets.
Black carbon in urban soils: land use and climate drive variation at the surface
Authors: Burke Molly , Marín-Spiotta Erika , Ponette-González Alexandra G. 
Published: March 2024

Abstract
Background
Black carbon (BC) encompasses a range of carbonaceous materials––including soot, char, and charcoal––derived from the incomplete combustion of fossil fuels and biomass. Urban soils can become enriched in BC due to proximity to these combustion sources. We conducted a literature review of BC in urban soils globally and found 26 studies reporting BC and total organic carbon (TOC) content collected to a maximum of 578 cm depth in urban soils across 35 cities and 10 countries. We recorded data on city, climate, and land use/land cover characteristics to examine drivers of BC content and contribution to TOC in soil.

Results
All studies were conducted in the northern hemisphere, with 68% of the data points collected in China and the United States. Surface samples (0–20 cm) accounted for 62% of samples in the dataset. Therefore, we focused our analysis on 0–10 cm and 10–20 cm depths. Urban soil BC content ranged from 0–124 mg/g (median = 3 mg/g) at 0–10 cm and from 0–53 mg/g (median = 2.8 mg/g) at 10–20 cm depth. The median proportional contribution of BC to TOC was 23% and 15% at 0–10 cm and 10–20 cm, respectively. Surface soils sampled in industrial land use and near roads had the highest BC contents and proportions, whereas samples from residential sites had among the lowest. Soil BC content decreased with mean annual soil temperature.

Conclusions
Our review indicates that BC comprises a major fraction (nearly one quarter) of the TOC in urban surface soils, yet sampling bias towards the surface could hide the potential for BC storage at depth. Land use emerged as an importer driver of soil BC contents and proportions, whereas land cover effects remain uncertain. Warmer and wetter soils were found to have lower soil BC than cooler and drier soils, differences that likely reflect soil BC loss mechanisms. Additional research on urban soil BC at depth and from diverse climates is critical to better understand the role of cities in the global carbon cycle.
Cox proportional hazard-model application: time to cervical cancer screening among women living with HIV in South Africa
Authors: Hollington Marcus 
Published: March 2024

Abstract
Background
There is an increased risk of cervical cancer among women living with HIV. While studies have long examined the association between cervical cancer among women with HIV, no study has examined the time taken for women with HIV to undergo cervical cancer screening as well as the hazard thereof in South Africa.

Methods
The study used cross-sectional data from the 2016 South Africa Demographic and Health Survey. To allow for longitudinal analysis and to address the issue of right-censoring, the data were reformatted to a person-data file. The selection criteria were limited to women living with HIV (WLHIV) who had also responded to the question on cervical cancer screening. Descriptive statistics were employed to show the levels of HIV among women aged 15 and older in South Africa. Additionally, Kaplan‒Meier curves were employed to investigate the time to CCS by WLHIV in South Africa. Thereafter, an unadjusted Cox hazards regression model was employed to examine the hazard of undergoing CCS among WLHIV. Finally, it employed an adjusted model to examine the hazard of CCS among WLHIV while adjusting for other factors.

Results
Nineteen percent (n = 1,159) of the women who participated in the study tested positive for HIV. Herein, it was found that the risk of CCS among WLHIV began at the age of approximately 19 years. Thereafter, the hazard of undergoing CCS among WLHIV began to decrease at 58 years. There was a significant association between CCS and WLHIV. Additionally, several covariates were found to be significantly associated with HIV. These were race, province, area of residence, marriage, educational attainment, employment, alcohol consumption, perceived health perception, and health insurance.

Conclusion
The hazard of CCS was lower among WLHIV compared to WLHIV who did not undergo CCS in South Africa. This puts HIV-positive women at risk of increased morbidity and mortality from potential cervical cancer and HIV comorbidity due to CCS deficits within this group. This is because they are susceptible to HPV and subsequent cervical cancer due to a compromised immune system. HIV-positive women need to routinely undergo CCS every 12 months from baseline for 3 years. Thereafter, they should undergo CCS once every 3 years to reduce their risk of developing the disease.
Associations of maternal serum concentration of iron-related indicators with birth outcomes in Chinese: a pilot prospective cohort study
Authors: Chen Geng-dong , Li Peng-sheng , Zhou Zi-xing , Wang Hai-yan , Gou Xiao-yan , Ye Shao-xin , Lin Dong-xin , Fan Da-zhi , Wang Li-juan , Liu Zheng-ping 
Published: March 2024

Abstract
Background
Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators.

Methods
A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects’ blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records.

Results
After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with − 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively.

Conclusions
Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.
Contribution of Anopheles gambiae sensu lato mosquitoes to malaria transmission during the dry season in Djoumouna and Ntoula villages in the Republic of the Congo
Authors: Mbama Ntabi Jacques Dollon , Malda Bali Espoir Divin , Lissom Abel , Akoton Romaric , Djontu Jean Claude , Missontsa Georges , Mouzinga Freisnel Hermeland , Baina Marcel Tapsou , Djogbenou Luc , Ndo Cyrille , Wondji Charles , Adegnika Ayola Akim , Lenga Arsène , Borrmann Steffen , Ntoumi Francine 
Published: March 2024

Abstract
Background
Mosquitoes belonging to the Anopheles gambiae sensu lato complex play a major role in malaria transmission across Africa. This study assessed the relative importance of members of An. gambiae s.l. in malaria transmission in two rural villages in the Republic of the Congo.

Methods
Adult mosquitoes were collected using electric aspirators from June to September 2022 in Djoumouna and Ntoula villages and were sorted by taxa based on their morphological features. Anopheles gambiae s.l. females were also molecularly identified. A TaqMan-based assay and a nested polymerase chain reaction (PCR) were performed to determine Plasmodium spp. in the mosquitoes. Entomological indexes were estimated, including man-biting rate, entomological inoculation rate (EIR), and diversity index.

Results
Among 176 mosquitoes collected, An. gambiae s.l. was predominant (85.8%), followed by Culex spp. (13.6%) and Aedes spp. (0.6%). Three members of the An. gambiae s.l. complex were collected in both villages, namely An. gambiae sensu stricto (74.3%), Anopheles coluzzii (22.9%) and Anopheles arabiensis (2.8%). Three Plasmodium species were detected in An. gambiae s.s. and An. coluzzii (Plasmodium falciparum, P. malariae and P. ovale), while only P. falciparum and P. malariae were found in An. arabiensis. In general, the Plasmodium infection rate was 35.1% (53/151) using the TaqMan-based assay, and nested PCR confirmed 77.4% (41/53) of those infections. The nightly EIR of An. gambiae s.l. was 0.125 infectious bites per person per night (ib/p/n) in Djoumouna and 0.08 ib/p/n in Ntoula. The EIR of An. gambiae s.s. in Djoumouna (0.11 ib/p/n) and Ntoula (0.04 ib/p/n) was higher than that of An. coluzzii (0.01 and 0.03 ib/p/n) and An. arabiensis (0.005 and 0.0 ib/p/n).

Conclusions
This study provides baseline information on the dominant vectors and dynamics of malaria transmission in the rural areas of the Republic of the Congo during the dry season. In the two sampled villages, An. gambiae s.s. appears to play a predominant role in Plasmodium spp. transmission.

Graphical Abstract
Causal relationship between diabetes mellitus, glycemic traits and Parkinson’s disease: a multivariable mendelian randomization analysis
Authors: Wang Qitong , Cai Benchi , Zhong Lifan , Intirach Jitrawadee , Chen Tao 
Published: March 2024

Abstract
Background
Observational studies have indicated an association between diabetes mellitus (DM), glycemic traits, and the occurrence of Parkinson’s disease (PD). However, the complex interactions between these factors and the presence of a causal relationship remain unclear. Therefore, we aim to systematically assess the causal relationship between diabetes, glycemic traits, and PD onset, risk, and progression.

Method
We used two-sample Mendelian randomization (MR) to investigate potential associations between diabetes, glycemic traits, and PD. We used summary statistics from genome-wide association studies (GWAS). In addition, we employed multivariable Mendelian randomization to evaluate the mediating effects of anti-diabetic medications on the relationship between diabetes, glycemic traits, and PD. To ensure the robustness of our findings, we performed a series of sensitivity analyses.

Results
In our univariable Mendelian randomization (MR) analysis, we found evidence of a causal relationship between genetic susceptibility to type 1 diabetes (T1DM) and a reduced risk of PD (OR = 0.9708; 95% CI: 0.9466, 0.9956; P = 0.0214). In our multivariable MR analysis, after considering the conditions of anti-diabetic drug use, this correlation disappeared with adjustment for potential mediators, including anti-diabetic medications, insulin use, and metformin use.

Conclusion
Our MR study confirms a potential protective causal relationship between genetically predicted type 1 diabetes and reduced risk of PD, which may be mediated by factors related to anti-diabetic medications.
Cytogenetics investigation in 151 Brazilian infertile male patients and genomic analysis in selected cases: experience of 14 years in a public genetic service
Authors: Adriano Márcia Regina Gimenes , Bortolai Adriana , Madia Fabricia Andreia Rosa , da Silva Carvalho Gleyson Francisco , Nascimento Amom Mendes , Zanardo Evelin Aline , Wolff Beatriz Martins , Waisberg Jaques , Bos-Mikich Adriana , Kulikowski Leslie Domenici , Dias Alexandre Torchio 
Published: March 2024

Abstract
Objectives
Male infertility accounts for approximately 30% of cases of reproductive failure. The characterization of genetic variants using cytogenomic techniques is essential for the adequate clinical management of these patients. We aimed to conduct a cytogenetic investigation of numerical and structural rearrangements and a genomic study of Y chromosome microdeletions/microduplications in infertile men derived from a single centre with over 14 years of experience.

Results
We evaluated 151 infertile men in a transversal study using peripheral blood karyotypes and 15 patients with normal karyotypes through genomic investigation by multiplex ligation-dependent probe amplification (MLPA) or polymerase chain reaction of sequence-tagged sites (PCR-STS) techniques. Out of the 151 patients evaluated by karyotype, 13 presented chromosomal abnormalities: two had numerical alterations, and 11 had structural chromosomal rearrangements. PCR-STS detected a BPY2 gene region and RBMY2DP pseudogene region microdeletion in one patient. MLPA analysis allowed the identification of one patient with CDY2B_1 and CDY2B_2 probe duplications (CDY2B and NLGN4Y genes) and one patient with BPY2_1, BPY2_2, and BPY2_4 probe duplications (PRY and RBMY1J genes).