bluuebunny/crossref_metadata_2025_split huggingface dataset:
The deubiquitinating enzyme USP4 regulates BRCA1 stability and function
Authors: Shao Genze , Guo Xueyuan , Ma Yanfang , Liu Runyu , Zhang Ting , Li Qin , Chang Fen , Deng Jingcheng , Duan Junyi , Li Li , Su Yanrong 
Published: July 2023

Abstract

BRCA1 plays a suppressive role in breast tumorigenesis. Ubiquitin-dependent degradation is a common mechanism that regulates BRCA1 protein stability, and several ubiquitin ligases involved have been identified. However, the deubiquitinating enzyme for BRCA1 remains less defined. Here, we report that the deubiquitinase USP4 interacts with, deubiquitinates and stabilizes BRCA1, maintaining the protein level of BRCA1. USP4 knockdown results in a decreased BRCA1 protein level, impairment in homologous recombination mediated double-stranded break repair, and increased genome instability, and confers resistance to DNA damage-inducing agents and PARP inhibitors. Ectopic expression of USP4 stabilizes BRCA1 and reverse the effects caused by USP4 knockdown. Moreover, USP4 is low expressed in human breast cancer tissues and its low expression correlates with poorer survival of patients. Furthermore, we identified several loss-of-function mutations of USP4 in human gynecological cancers, the catalytic activity of which or their interaction with BRCA1 is disrupted. Together, we reveal that USP4 is a deubiquitinase for BRCA1. USP4 positively regulates the stability and function of BRCA1 through deubiquitination, and plays important role in the suppression of breast cancer.
Neoadjuvant Immunotherapy combined with Chemoradiotherapy VS. Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma(cStageII-III): A Multi-center Prospective Randomized Clinical Trial
Authors: Huang Xu , Tang Han , Jiao Heng , Yin Jun , Wang Hao , Xu Wenyi , Yin Hao , Yang Shuyi , Wang Qingle , Zeng Mengsu , Jiang Dongxian , Hou Yingyong , Du Shisuo , Zeng Zhaochong , Li Yin , Chen Keneng , Li Zhigang , Han Yongtao , Shen Weiyu , Chen Qixun , Jiang Hongjing , Fan Hong , Jiang Bo , Liao Yongde , Tan Lijie 
Published: July 2023

Abstract
background
Neoadjuvant chemoradiotherapy (nCRT) combined with surgery has been suggested as the standard treatment for locally advanced ESCC. Meanwhile, CHECKMATE-577 has suggested that immunotherapy may be effective in controlling tumor recurrence and metastasis. According to PALACE-1, Neoadjuvant radiotherapy and chemotherapy combined with immunity may be more beneficial for patients. Therefore, it is meaningful to further study whether the combination of nCRT and immunotherapy has better effects in the treatment of ESCC.
methods
NCT04973306 is designed as a multicenter, prospective, randomized, Phase II/Phase III clinical trial discussion, investigating the safety and efficacy of nCRT plus tumor immunotherapy compared with nCRT. A total of 476 patients with locally advanced resectable ESCC (stage cII-III) are randomly assigned to neoadjuvant immunotherapy combined with chemoradiotherapy (arm A) or nCRT (arm B) with a 1:1 allocation ratio. The primary endpoint of the first phase of the study was pCR. Overall survival assessed with a minimum follow-up of 36 months served as the study's main goal during the second phase (OS). Secondary outcomes are R0 resection rate, positive lymph node rate and response, number of lymph nodes cleared, tumor regression grade (TRG) of primary tumor, and disease-free survival (DFS) between the two groups
discussion
This trial aims to study whether nCRT plus tumor immunotherapy yields superior benefits for curative treatment of ESCC and the survival. Trial registration number is NCT04973306.
Deep learning-based Fast Volumetric Image Generation for Image-guided Proton FLASH Radiotherapy
Authors: Chang Chih-Wei , Lei Yang , Wang Tonghe , Tian Sibo , Roper Justin , Lin Liyong , Bradley Jeffrey , Liu Tian , Zhou Jun , Yang Xiaofeng 
Published: July 2023

Abstract
Objective: FLASH radiotherapy leverages ultra-high dose-rate radiation to enhance the sparing of organs at risk without compromising tumor control probability. This may allow dose escalation, toxicity mitigation, or both. To prepare for the ultra-high dose-rate delivery, we aim to develop a deep learning (DL)-based image-guide framework to enable fast volumetric image reconstruction for accurate target localization for proton FLASH beam delivery.
Approach: The proposed framework comprises four modules, including orthogonal kV x-ray projection acquisition, DL-based volumetric image generation, image quality analyses, and water equivalent thickness (WET) evaluation. We investigated volumetric image reconstruction using kV projection pairs with four different source angles. Thirty patients with lung targets were identified from an institutional database, each patient having a four-dimensional computed tomography (CT) dataset with ten respiratory phases. Leave-phase-out cross-validation was performed to investigate the DL model’s robustness for each patient.
Main results: The proposed framework reconstructed patients’ volumetric anatomy, including tumors and organs at risk from orthogonal x-ray projections. Considering all evaluation metrics, the kV projections with source angles of 135° and 225° yielded the optimal volumetric images. The patient-averaged mean absolute error, peak signal-to-noise ratio, structural similarity index measure, and WET error were 75±22 HU, 19±3.7 dB, 0.938±0.044, and -1.3%±4.1%.
Significance: The proposed framework has been demonstrated to reconstruct volumetric images with a high degree of accuracy using two orthogonal x-ray projections. The embedded WET module can be used to detect potential proton beam-specific patient anatomy variations. This framework can rapidly deliver volumetric images to potentially guide proton FLASH therapy treatment delivery systems.
Bioelectrical impedance and lung function - associations with gender and central obesity: results of the EpiHealth study
Authors: Qvarfordt Mikaela , Lampa Erik , Cai Gui-Hong , Lind Lars , Elmståhl Sölve , Svartengren Magnus 
Published: July 2023

Abstract
Background
Obesity is associated with various health problems, including respiratory impairment; moreover, it is a major public health concern. There is a lack of a consensus in healthcare on how body fat should be assessed in relation to lung function. In this study, we aimed to investigate how bioelectrical impedance contributes to predicting reduced lung function in relation to waist circumference in cases of increased adipose tissue, using data from a large Swedish population study.
Methods
In total, 22,706 participants (aged 45–75 years) were included in the study. The relationships between fat mass, waist circumference, and lung function were analysed using weighted quantile sum regression.
Results
The results showed that waist circumference was more important than trunk fat mass (variable weights 0.68 and 0.28, respectively) in men, but the opposite was true for waist circumference and trunk fat in women (variable weights 0.23 and 0.77). Both sexes were significantly associated with decreased lung function (FEV1, FVC, and z-scores).
Conclusions
Our results suggest that trunk fat should be considered when assessing the impact of adipose tissue on lung function and should potentially be included in the health controls.
Adverse Childhood Experience, Parental Bonding, and Fatherhood as Parenting Vulnerabilities to Social Anxiety Severity in Iranian Context
Authors: Heshmati Rasoul , Abbasoghli Parisa Haji , Pour Nazanin Seyed Yaghoubi , Asgarabad Mojtaba Habibi 
Published: July 2023

Abstract

The present study aimed to examine the association between adverse childhood experiences, parental bonding, fatherhood, and social anxiety symptoms among emerging adults in an Iranian context. In a cross-sectional study, self-reports measuring fatherhood, parental bonding, anxious thoughts, and childhood trauma were administered to 242 university students with social anxiety symptoms. The data were analyzed using multiple linear regression. Individuals with adverse childhood experiences displayed more social anxiety symptoms (R2 = .32) than others. Moreover, fatherhood (R2 = .28), paternal bonding (R2 = .26), and maternal bonding (R2 = .26) were all significantly and equally associated with variance in social anxiety symptoms. Our findings revealed that adverse childhood experiences, fatherhood, and both maternal and paternal bonding significantly correlated to social anxiety symptoms later in adulthood. Accordingly, it is vital to assess the significance of each factor that contributes to social anxiety in order to develop community-based prevention packages and reduce the prevalence of social anxiety in society.
Designing Transparent Piezoelectric Metasurfaces for Adaptive Optics
Authors: Li Fei , Qiao Liao , Gao Xiangyu , Ren Kaile , Qiu Chaorui , Liu Jinfeng , Jin Haonan , Dong Shuxiang , Xu Zhuo 
Published: July 2023

Abstract
Simultaneously generating various vibration modes with ultrahigh strains in a piezoelectric device is highly desired for high-technology fields to achieve multi-functionalities. However, the traditional approach for designing multi-degrees-of-freedom systems is to bond together several multilayer piezoelectric stacks, which generally leads to a cumbersome and complicated structure. Here, we proposed to achieve various types of ultrahigh strains in a wide frequency range by using a transparent piezo matasurface (PM). As an example, a PM consisting of ten pieces of transparent Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 (PIMNT) single crystal units was designed and characterized. The newly designed PM can produce ultrahigh strains (ε3 = 0.38%), and thus generate the linear motions along the X-, Y- and Z-axis, the rotary motions around the X-, Y- and Z-axis as well as the coupled motions. A PM adaptive lens with both autofocus (AF) and optical image stabilization (OIS) functions was demonstrated in the present work. The PM adaptive lens can realize a wide range of focal length (35.82 cm to ∞) and the effective image stabilization with relatively large displacements (i.e., 5.05 μm along the Y-axis) and tilt angles (i.e., 44.02′ around the Y-axis). This research may inspire miniaturization and integration for multi-degrees-of-freedom systems.
Application of the Boruta Algorithm to assess the multi-dimensional determinants of malnutrition among children under five years living in southern Punjab, Pakistan
Authors: Saleem Javeria , Zakar Rubeena , Butt Muhammad Salman , Aadil Rana Muhammad , Ali Zulfiqar , Bukhari Gul Mehar Javaid , Ishaq Muhammad , Fischer Florian 
Published: July 2023

Abstract
Background: A nutrient deficit caused by malnutrition has physical and clinical manifestations. Globally, there were 47 million wasted children under the age of five in 2019. One in four were located in sub-Saharan Africa, with half being in South Asia. This study aims to apply the Boruta algorithm to identify the determinants for malnutrition among children under five living in Dera Ghazi Khan one of the marginalized districts of densely populated Punjab province in Pakistan.
Methods: A multicenter cross-sectional study design was used to collect data from 185 severe acute malnutrition children aged under five years visiting the OTPs centers located in Dera Ghazi Khan, Punjab, Pakistan. A purposive sampling technique was used to collect data using a pretested structured questionnaire from parents/caregivers regarding family sociodemographic characteristics, child nutrition, and biological and healthcare characteristics. Anthropometric measurements including height, weight, and mid-upper arm circumference were collected. The data was analyzed using the Boruta package in R studio.
Results: This study included 185 children, with a mean age of 15.36 ± 10.23 months and had MUAC of 10.19 ± 0.96 cm. Boruta analysis identifies age, mid-upper arm circumference, weaning practices, and immunization status as significant determinants for weight-for-height prediction in children under five. The study identifies Boruta algorithm determinants for weight-for-age prediction, with MUAC and Income per month as confirmed. Under five age, income per month, exclusive breastfeeding and immunization status resulted as important determinants for undernutrition.
Conclusion: Age, weaning methods, immunization status, and household income are all associated with malnutrition and undernutrition in children under five. Malnutrition must be addressed by collaborative efforts from all areas, including dietary knowledge and growth factors.
Liver X receptor alpha ensures blood-brain barrier function by suppressing SNAI2
Authors: de Wit Nienke , Vacondio Davide , Nogueira-Pinto Henrique , Coenen Loet , Mulder Inge , Fontijn Ruud , Hof Bert van het , Fung Wing Ka , Jongejan Aldo , Kooij Gijs , Rozemuller Annemieke , Zelcer Noam , de Vries Helga 
Published: July 2023

Abstract
In Alzheimer’s disease (AD) more than 50% of the patients are affected by capillary cerebral amyloid-angiopathy (capCAA), which is characterized by localized hypoxia, neuro-inflammation and loss of blood-brain barrier (BBB) function. Moreover, AD patients with or without capCAA display increased vessel number, indicating a reactivation of the angiogenic program. The molecular mechanism(s) responsible for BBB dysfunction and angiogenesis in capCAA is still unclear, preventing a full understanding of disease pathophysiology. The Liver X receptor (LXR) family, consisting of LXRα and LXRβ, was reported to inhibit angiogenesis and particularly LXRα was shown to secure BBB stability, suggesting a major role in vascular function. In this study we unravel the regulatory mechanism exerted by LXRα to preserve BBB integrity in human brain endothelial cells (BECs) and investigate its role during pathological conditions. We report that LXRα ensures BECs identity via constitutive inhibition of the transcription factor SNAI2. Accordingly, deletion of brain endothelial LXRα is associated with impaired DLL4-NOTCH signalling, a critical signalling pathway involved in vessel sprouting. A similar response was observed when BECs were exposed to hypoxia, with concomitant LXRα decrease and SNAI2 increase. In support of our cell-based observations, we report a general increase in vascular SNAI2 in the occipital cortex of AD patients with and without capCAA. Importantly, SNAI2 strongly associated with vascular amyloid beta deposition and angiopoietin like 4, a marker for hypoxia. In hypoxic capCAA vessels, the expression of LXRα may decrease leading to an increased expression of SNAI2, and consequently BECs de-differentiation and sprouting. Our findings indicate that LXRα is essential for BECs identity, thereby securing BBB stability and preventing aberrant angiogenesis. These results uncover a novel molecular pathway essential for BBB identity and vascular homeostasis providing new insights on the vascular pathology affecting AD patients.
Small RNA sequencing provides insights into molecular mechanism of flower development in Rhododendron pulchrum Sweet
Authors: Fang Bo , Huang Zhiwei , Sun Yirong , Zhang Wanjing , Yu Jiaojun , Zhang Jialiang , Dong Hongjin , Wang Shuzhen 
Published: July 2023

Abstract
Rhododendron pulchrum Sweet, a member of the Ericaceae family possessing valuable medicinal and horticultural properties, is widely distributed in the temperate regions. Though serving as bioindicator of metal pollution, the molecular mechanism regulating flowering in R. pulchrum is very limited. Illumina sequencing was performed to clarify the function of miRNAs in the synthesis of anthocyanin at different developmental stages. Totally, 722 miRNAs belonging to 104 families were screened, and 84 novel mature miRNA sequences were predicted. The miR166, miR156, and miR167-1 were dominant families. In particular, 126 miRNAs were significantly differentially expressed among four different flowering stages. Based on integrated GO and KEGG function annotations, the miRNA target genes were mostly involved in metabolic pathways, plant hormone signal transduction, mitosis and regulation of biosynthetic processes. Totally, 593 genes were differentially regulated by miRNAs during the flower development process. In pigment biosynthesis and signal transduction processes, gra-miR750 significantly regulated the expression of flavonoid 3’,5’-hydroxylase; aof-miR171a, aof-miR171b, aof-miR171c, cas-miR171a-3p, and cas-miR171c-3p could regulate the expression of DELLA protein; aof-miR390, aof-miR396b, ath-miR3932b-5p, cas-miR171a-3p, aof-miR171a, and aof-miR171b regulated BAK1 expression. This research showed great potentials for genetic improvement of flower color traits for R. pulchrum and other Rhododendron species.
Immigration Status and Chronic Disease Outcomes – a Scoping Review
Authors: Rivers Patrick , Palmer Kelly N.B. , Okechukwu Abidemi , McClelland D. Jean , Garcia David O. , Sun Xiaoxiao , Pogreba-Brown Kristen , Carvajal Scott C. , Marrero David G. 
Published: July 2023

Abstract
Background
Undocumented immigrants face significant barriers to accessing regular medical care in the U.S. This is a concern especially for individuals with chronic conditions. This scoping review provides an overview of the current knowledge on chronic health outcomes for undocumented immigrants compared to documented immigrants or US-born citizens.
Methods
The review process was conducted in accordance with the PRISMA-ScR guidelines, and the selection of studies was based on pre-defined criteria.
Results
Nine articles were included. Key information such as population details, and study details, outcomes, and limitations are presented. There was conflicting evidence as to whether undocumented immigrants have poorer health outcomes, with undocumented immigrants faring better on nine (43%) measures, faring worse on nine (43%), and with no difference found on three (14%) measures when compared to documented immigrants or US-born citizens.
Conclusion
Undocumented individuals face significant barriers to accessing the same level of health care for their chronic conditions, but it is unclear if this translates to poorer health outcomes. Future, rigorous studies are recommended to address this gap and better understand the health of this vulnerable population.
Epidemiological survey and Genotype diversity of Mycoplasma pneumoniae in Guangxi China swine herds based on MLST
Authors: Zhou Ying , Chen Zhongwei , Lu Bingxia , Duan Qunpeng , Xiao Ting , Liang Longhua , Huang Yu , Duan Zhenhua , Wei Mingyu , He Ying 
Published: July 2023

Abstract

Background
Mycoplasma hyopmneumoniae (Mhp) is a swine pathogen bacterium, causing significant economic losses worldwide. In this study, total of 1362 samples of swine lung from 14 cities in Guangxi were collected randomly. And TaqMan Real-time PCR Detection Method was applied in the detection of Mhp. The strongly positive samples were used in the multilocus sequence typing (MLST). The purpose of this study is to investigate the prevalence of Mhp in Guangxi and to reveal the genotypes and distribution of Mhp in swine herds in Guangxi based on MLST.
Results
Out of 1362 samples, 655 samples were detected mhp positive. Among them 61 samples were successfully amplified three housekeeping genes (adk, rpoB and tpiA) simultaneously using MLST method. What is more, this study recorded 27 sequence types from 14 cities in Guangxi Province, including 24 new STs. From genetic evolution tree analysis, it can be revealed that the prevalent strains of Mhp in Guangxi, China are types II and V. All in all, the Mhp popular in Guangxi China have a high genetic diversity.
Conclusions
This is one of the most comprehensive study available for reporting the prevalence and molecular typing of Mhp in Guangxi China which will enrich the local database of Mhp prevalence in China and provide a theoretical basis for the prevention and control of Mhp in the Guangxi region of China.
Virological suppression rate and its predictors among HIV/AIDS patients on antiretroviral therapy before and during the COVID-19 pandemic in Ethiopia: Systematic review and meta-analysis
Authors: Melak Dagnachew , Bayou Fekade Demeke , Yasin Husniya , Zerga Aregash Abebayehu , Wagaye Birhanu , Ayele Fanos Yeshanew , Kebede Natnael , Mekonen Asnakew Molla , Asfaw Ahmed Hussien , Mihiretu Mengistu Mera , Tsega Yawkal , Addisu Elsabeth , Cherie Niguss , Birhane Tesfaye , Abegaz Zinet , Endawkie Abel , Mohammed Anissa 
Published: July 2023

Abstract
Background
Achieving viral load suppression is crucial for the prevention of complications and deaths related to HIV infection. Ethiopia has embraced the worldwide 90-90-90 target, but there is no national representative information regarding virological suppression. Therefore, this review aims to determine the pooled virological suppression rate and identify the pooled effect of contributing factors of viral suppression for HIV-positive patients on antiretroviral therapy in Ethiopia.
Method
We systematically searched websites and databases, including online repositories, to obtain primary studies. We assessed the quality of the included articles using the Newcastle‒Ottawa Scale appraisal checklist by two reviewers. Publication bias was checked using Egger’s regression test, the heterogeneity of the studies was assessed using I2 statistics and Q statistics, and sensitivity analysis was performed to identify any outlier results in the included studies. The Der Simonian Laird random-effects model was used to estimate the overall proportion of viral suppression, and STATA 17 statistical software was used for all types of analysis.
Result
A total of 21 eligible articles were used for this quantitative synthesis. The overall pooled virological suppression was 71% (95% CI: 64%, 77%). The pooled effects of poor adherence to ART (AOR = 0.33; 95% CI: 0.28, 0.40), body mass index (18.5–24.9 kg/m2) (AOR = 1.8; 95% CI: 1.37, 2.36), disclosure AOR = 1.41; 95% CI: 1.05, 1.89), absence of opportunistic infection (AOR = 1.68; 95% CI: 1.43, 1.97), and high baseline viral load (AOR = 0.65; 95% CI: 0.52, 0.81) were identified as significant predictors of viral suppression.
Conclusion
The overall pooled percentage of virological suppression was low compared with the global target of viral suppression. Poor adherence, normal body mass index, disclosure, absence of opportunistic infection and high viral load were contributing factors of viral suppression in Ethiopia. Responsible stakeholders should maximize their effort to achieve the global target of virological suppression by addressing significant predictors.
Prospero registration number and google link: CRD42023434248.
Development of a new endometrial microRNA-based signature for identifying window of implantation
Authors: Chen Ching Hung , Lu Farn , Yang Wen Jui , Chen Wei Ming , Yang Eric Pok , Kang Shih Ting , Wang Tiffany , Chang Po Chang , Huang Yu Shan , Feng Chi Ting , Yang Jung-Hsuan , Liu Chen-Yu , Hsieh Chi-An , Wang Lily Hui-Ching , Huang Jack Yu Jen 
Published: July 2023

Abstract
Though tremendous advances have been made in the field of in vitro fertilization (IVF), a portion of patients are still troubled by embryo implantation failure issues. One of the significant factors contributing to implantation failure is a uterine condition called the displaced window of implantation (WOI), which results in an unsynchronized endometrium and embryo transfer time for IVF patients during treatment. Previous studies have shown that microRNAs (miRNAs) can be important indicators in the reproductive process, regulating important functions such as embryo development, organ development, and cytokinesis. In this study, we have built and validated a microRNA-based prediction model for analyzing endometrial receptivity to identify the WOI of patients undergoing frozen embryo transfer cycles. Based on miRNA biomarkers’ expression profiles, a miRNA-based classifier was built with an accuracy of 94% in the training set and 89% in the testing set, showing high promise in accurately identifying the ideal time for embryo transfer (WOI).