bluuebunny/crossref_metadata_2025_split huggingface dataset:
RRM2 and CDC6 are novel effectors of XBP1-mediated endocrine resistance and predictive markers of tamoxifen sensitivity
Authors: Barua David , Sultana Afrin , Islam Md Nahidul , Cox Fergus , Gupta Ananya , Gupta Sanjeev 
Published: August 2022

Abstract
Background
Endocrine-resistant breast cancers have elevated expression of XBP1, where it drives endocrine resistance by controlling the expression of its target genes. Despite the in-depth understanding of the biological functions of XBP1 in ER-positive breast cancer, effectors of endocrine resistance downstream of XBP1 are poorly understood. The aim of this study was to understand the XBP1-mediated novel targets in endocrine resistant breast cancer.
Methods
XBP1 deficient sub-clones in MCF7 cells were generated using the CRISPR-Cas9 gene knockout strategy and were validated using western blot and RT-PCR. Cell viability and cell proliferation were evaluated using the MTS assay and colony formation assay, respectively. Cell death and cell cycle analysis were determined using flow cytometry. Transcriptomic data from the gene expression omnibus dataset (GSE49955) was analysed to identify XBP1-regulated targets. The expression of target molecules was determined using western blot and qRT-PCR. Lentivirus and retrovirus transfection were used to generate RRM2 and CDC6 overexpressing clones, respectively. The prognostic value of the XBP1-gene signature was analysed using Kaplan-Meier survival analysis.
Results
Deletion of XBP1 compromised the upregulation of UPR-target genes during conditions of endoplasmic reticulum (EnR) stress and sensitized cells to EnR stress-induced cell death. Loss of XBP1 in MCF7 cells decreased cell growth, attenuated the induction of estrogen-responsive genes and sensitized them to anti-estrogen agents. The expression of cell cycle associated genes RRM2, CDC6, and TOP2A was significantly reduced upon XBP1 deletion/inhibition in several ER-positive breast cancer cells. Expression of RRM2, CDC6, and TOP2A was increased upon estrogen stimulation and in cells harbouring point-mutants (Y537S, D538G) of ESR1 in steroid free conditions. Ectopic expression of RRM2 and CDC6 increased cell growth and reversed the hypersensitivity of XBP1 KO cells towards tamoxifen conferring endocrine resistance. Importantly, increased expression of XBP1-gene signature was associated with poor outcome and reduced efficacy of tamoxifen treatment in ER-positive breast cancer.
Conclusions
Our results suggest that RRM2 and CDC6 downstream of XBP1 contribute to endocrine resistance in ER-positive breast cancer. XBP1-gene signature is associated with poor outcome and response to tamoxifen in ER-positive breast cancer.
Genetic diversity and population structure of Ugandan soybean (Glycine max (L.) germplasm based on DArTseq
Authors: Lukanda Musondolya Mathe , Dramadri Isaac Onziga , Adjei Emmanuel Amponsah , Perpetua Arusei , Gitonga Hellen Wairimu , Wasswa Peter , Edema Richard , Ssemakula Mildred Ochwo , Tukamuhabwa Phinehas , Geoffrey Tusiime 
Published: August 2022

Abstract
Soybean (Glycine max (L.) is an important oil crop with production below the real need in Africa. To increase the production, substantial upgrading must be accomplished by enlarging the genetic potential of new cultivars that relays on the parents' genetic diversity. We aimed to assess the genetic diversity and the population structure of soybean accessions, therefore, evaluate soybean value in terms of use for breeding purposes. To accomplish this, a set of 282 soybean accessions were genotyped using the Diversity Array Technology Sequencing with a high throughput of the Single-nucleotide polymorphisms (SNPs). A total of 6,935 high-quality SNPs were identified across the whole soybean genome. The mean value of genetic diversity, major alleles frequency, minor alleles frequency, expected heterozygosity, and the polymorphism information content was respectively estimated at 0.35, 0.77, 0.22, 0.33, and 0.29. The analysis of molecular variance reveals that the variance among the populations is lower than the variance within the populations. The soybean accessions could be classified into two groups based on the model-based population structure and the principal coordinate analysis or into three groups based on the discriminant analysis of the principal component and the Neighbor-joining tree. The information provided in this study will be helpful for breeders.
A scalable optical computer based on free-space optics using lens arrays and a spatial light modulator
Authors: Ju Young-Gu 
Published: August 2022

Abstract
A scalable optical computer based on free-space optics was proposed to obtain optical parallelism in an artificial neural network. The combination of lens arrays, a spatial light modulator, and a large-diameter lens can distribute the weighted input light to multiple detectors, which can add light from multiple inputs to achieve a linear combination optical engine. The nonlinear part of the neural network can be processed using distributed electronics, as in smart pixels. The proposed design was realised in hardware with 2×2 inputs and 2×2 outputs, using light-emitting diodes, a liquid crystal display, lens arrays, and a detector array assembled in an optical cage system with subsidiary electronics. The feasibility of the constructed optical computer was demonstrated by achieving the expected results of NAND and NOR logics in parallel in the non-difference mode. A simple pattern-checking function in the difference mode was also shown. The proposed architecture has the potential for realising massive optical parallelism if large array components and high-speed electronics are used in the future.
How Can We Meet the Diverse Needs of Patients, Their Families and Their Communities? A Qualitative Study Including Clinicians, Consumer Representatives, Patients, and Community Stakeholders.
Authors: Roberts Natasha , Jacmon Helene , Scanlon Brighid , Battersby Chrissy , Buttrum Peter , James Christine 
Published: August 2022

Abstract
Background:The Diversity Working Group was formed to provide guidance to implement hospital health services strategies that could better address the diverse needs of patients and communities, with particular attention to those at greater risk of harm. It was identified that a better understanding of gaps in patient facing areas was required.Methods:A qualitative study was conducted by an experienced team from varied professional backgrounds including a clinician researcher, a nurse researcher with expertise in culturally and linguistically diverse community care and a consumer representative with expertise in advocacy and carer representation. Qualitative questions were co-designed, aiming to identify enablers and barriers to person-centred care. Community stakeholders, and clinical staff and patients from both ambulatory and inpatient areas were approached to participate. Responses were coded independently and synthesised using a Framework Approach. ResultsIn total 3 community stakeholders, 40 clinical staff and 30 patients consented to participate in the qualitative study over a period of three weeks. There were three key themes across responses, ‘What are diverse needs?’; ‘Assigning people to a group does not identify a diverse need’; ‘Unplanned care amplifies diverse needs’. Those patients who were isolated, for any number of reasons, were identified as at greatest risk of harm. Conclusion:Taking a person-centred approach can potentially ensure that the diverse needs of patients and communities will be better identified and responded to. Resources are needed to support patients and their families at times of transition care, particularly when care is unplanned.
Trophic ontogeny of a generalist predator is conserved across space
Authors: Stallings Christopher D , Nelson James A , Peebles Ernst B , Ellis Gregory , Goddard Ethan A , Jue Nathaniel K , Mickle Alejandra , Tzadik Orian E , Koenig Christopher C 
Published: August 2022

Abstract
Consumers can influence ecological patterns and processes through their trophic roles and contributions to the flow of energy through ecosystems. However, the diet and associated trophic roles of consumers commonly changes during ontogeny. Despite the prevalence of ontogenetic variation in trophic roles of most animals, we lack an understanding of whether they change consistently across local populations and broad geographic gradients. We examined how the diet and trophic position of a generalist marine predator varied with ontogeny across seven broadly separated locations (~ 750km). We observed a high degree of heterogeneity in prey consumed without evidence of spatial structuring in this variability. However, compound specific isotope analysis of amino acids revealed remarkably consistent patterns of increasing trophic position through ontogeny across local populations, suggesting that the roles of this generalist predator scaled with its body size across space. Given the high degree of diet heterogeneity we observed, this finding suggests that even though the dietary patterns differed, the underlying food web architecture transcended variation in prey species across locations for this generalist consumer. Our research addresses a gap in empirical field work regarding the interplay between stage-structured populations and food webs, and suggests ontogenetic changes in trophic position can be consistent in generalist consumers.
TCP1 promotes the progression of malignant tumors by stabilizing c-Myc through the AKT/GSK-3β and ERK signaling pathways
Authors: Chen Yuanzhong , Liu Hekun , Chen Linying , Jin Yiyi , Chen Xiance , Ma Nengjun , Yang Fan , Bi Huixia , Liu Wenwen , Wen Xinxin , Li Xinyan , Xu Shenmin , Xu Hongliang , Chen Juan , Lin Yanping , Chen Yuwen , Yang Yinghong , Wu Yong 
Published: August 2022

Abstract
TCP1, one of the subunits of molecular chaperone containing tailless complex polypeptide 1 (CCT) (CCT1), maybe play an essential role in cell proliferation and tumorigenesis. However, the biological functions and the underlying mechanisms of TCP1 in tumors are not fully understood. Here, we found that TCP1 levels increased with successive generations of xenografted tumors and were associated with the tumorigenicity of HL-60 cells. TCP1 expression was significantly higher in de novo and recurrent leukemia clinical samples and in various solid tumor tissues than in their related normal tissues. High expression of TCP1 was significantly associated with poor outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) and HCC. Functional assays and mechanistic studies revealed that TCP1 suppression not only decreased the proliferation and invasion of cancer cells in vitro but also inhibited tumor growth and metastatic spread in vivo. Ubiquitination assays and mechanistic studies revealed that TCP1 regulated the stability of c-Myc through the AKT/GSK-3β and ERK signaling pathways. Moreover, TCP1 knockin (TCP1-KI) mice, which generated by CRISPR/Cas9-mediated genome engineering, dramatically facilitated the occurrence of DEN-induced HCC. Our results demonstrate a novel mechanism of TCP1 regulation in multiple malignant tumors, and targeting TCP1 may provide new therapeutic strategies for the cancer treatment.
Numerical simulation model of reciprocating rod seal systems with axial wear texture on rod surface
Authors: Xiang Chong , Guo Fei , Jia Xiaogong , Wang Yuming 
Published: August 2022

Abstract
In this paper, a simulation model of reciprocating rod seal systems when there is axial texture on the rod surface due to wear is studied. The model includes macroscopic solid mechanics analysis, microscopic contact mechanics analysis and fluid mechanics analysis, and on this basis, the change of surface pressure when the sealing ring fall into a texture is calculated by the micro-deformation mechanics analysis of the seal surface. Then, the stiffness matrix method is used to find the film thickness when the three pressures in the sealing area are in equilibrium, completing the fluid-solid coupling calculation. Combined with the above simulation process, the performance parameters of the sealing system such as leakage and friction can be obtained. Results show that axial texture will degrade sealing performance, which increases leakage and friction. The simulation results can quantitative characterize the influence of rod wear on sealing performance and provide some theoretical basis for the study of seal failure mechanism and prediction of seal life.
Long-term and Short-term Memory Networks Based on Forgetting Memristors
Authors: Liu Yi , Chen Ling , Li Chuandong , Liu Xin , Zhou Wenhao , Li Ke 
Published: August 2022

Abstract
The hardware circuit of neural network based on forgetting memristor not only has the characteristics of high computational efficiency and low power consumption, but also has the advantage that a memristor can store the weight of long-term memory and short-term memory. Neural networks based on forgetting memristors can process two different data sets, however, the number of data sets processed is determined by the conversion rate of short-time memory network to long-term memory network. In this paper, a model of forgetting memristor with controllable decay rate is proposed, the voltage source signal is used to set the weight and decay rate of long and short-term memory, and the hardware simulation circuit of long-term and short-term memory(LSTM) network was built based on the forgetting memristor bridge array, and tested on KMNIST and FASHION-MNIST data sets. The experimental results show that the long-term memory network and the short-term memory network can be converted into each other in the LSTM network based on
Tbx4 and Tbx5 gene expression associated with appendage development and its relationship with the absence of a ventral fin in Pampus argenteus
Authors: Zhang Shun , Hu Lingzhu , Zhu Xiaojing , Liao Kai , Xu Shanliang , Wang Danli 
Published: August 2022

Abstract
Background
The Tbx family was first known through the study of their functions in the body and limbs, and its members Tbx4 and Tbx5 genes are important factors in determining the characteristics of the appendages. Pampus argenteus is an important fishery resource and an emerging target of aquaculture. It has a bizarre morphology, the lack of ventral fin. So, it is necessary to study the role of Tbx family genes in the deletion of pelvic fin in P. argenteus.
Results
Cloning Tbx4 and Tbx5 cDNA sequence of P. argenteus for the first time (GenBank: MH709128 and MH712458), which both contain highly conserved T-box region (DNA binding domain). In different developmental stages of P. argenteus, the expression of Tbx4 mRNA showed an overall "M" trend of increasing, then decreasing and then increasing again, with the highest peak at the age of 13 days old larvae; and a positive RNA hybridization signal was detected in the abdominal epithelium, while its protein expression was significantly inhibited. TBX4 protein expression was lowest in the abdominal epithelium and even inferior to its expression in the pectoral fin. At different developmental stages of P. argenteus, the expression of Tbx5 mRNA showed an overall trend of first increase and then decrease, and reached the highest at larvae 1 day (the appearance of pectoral fin primordium). Consistent with in situ hybridization, positive signals were concentrated in the heart and pectoral fins. The expression of TBX5 protein is basically consistent with the expression of mRNA, that is, when the expression of Tbx5 mRNA increases, its protein content also increases relatively, and after accumulation to a certain extent, the accumulation of pectoral fin cells begins to appear.
Conclusions
The translation of Tbx4 mRNA may be inhibited during the critical period of ventral fin development. Among different tissues, TBX4 protein levels were the lowest in the abdominal epithelium, and even lower than that in the pectoral fin, suggesting that the protein expression may be also inhibited in the abdominal epithelium of adult P. argenteus.
Fetal endothelial dysfunction in Gestational Diabetes Mellitus under Dietary or Insulin therapy
Authors: Wang Jing-Jing , Wang Xi , Li Qian , Hua Huang , Zheng Qiao-Ling , Yao Qin , Zhang Jun 
Published: August 2022

Abstract
Objective Gestational diabetes mellitus (GDM) is a serious pregnancy complication. Even if the plasma glucose levels were controlled with dietary intervention (GDM-D) or insulin therapy (GDM-I), children from diabetes mothers have increased rates of CVD from childhood to early adulthood. Endothelial function is a barometer of vascular health. The study was conducted to find out the changes in fetal endothelial dysfunction in GDM under different interventions in pregnancies. The primary HUVECs were separated from human normal pregnant (n=6), GDM-D (n=6), and GDM-I (n=6), respectively. Methods LC-MS/MS was used to identify differentially expressed proteins of primary HUVECs among the three groups and bioinformatics analysis was then performed. Glucose uptake, ATP level, apoptosis, as well as differentially protein was assessed to identify how the energy metabolism changed. Results A total of 8174 quantifiable proteins were detected, and 142 differentially expressed proteins were found both in comparison between the patients with GDM-D/GDM-I and healthy controls. 64 proteins were upregulated, while 77 were downregulated. Bioinformatics analysis revealed that differentially expressed proteins are involved in multiple biological processes and signaling pathways related to cellular process, biological regulation, and metabolic process. The PI3K/AKT signaling pathway was changed among the three groups. Glucose uptake was decreased in GDM-I (p<0.01). The expression of glucose transport 1 (Glut1) and glucose transporter 3 (Glut3) were decreased significantly in GDM-D and GDM-I. ATP levels were decreased both in GDM-D (p<0.01) and GDM-I (p<0.05). Apoptosis happened in the both GDM-D and GDM-I groups, while the expression of apoptosis-related protein cleaved caspase-3 and cleaved PARP have an increasing trend in the GDM-D and GDM-I. Compared with normal, the phosphate AKT and phosphate AMPK was reduced in GDM-D and GDM-I. Conclusions In summary, endothelial dysfunctions happened in pregnancies with GDM even though the plasma glucose levels were controlled. The energy dysfunction might be related to the regulation of the AKT/AMPK/mTOR signal pathway.
The effect of postoperative intravenous iron in anaemic, older cardiac surgery patients on disability-free survival (AGE ANEMIA study): Study protocol for a multi-centre, double blind, randomized, placebo-controlled trial.
Authors: Smoor Rosa M , Rettig Thijs CD , Vernooij Lisette M , Dongen Eric PA van , Noordzij Peter G 
Published: August 2022

Abstract
Background: Postoperative anaemia is common in older cardiac surgery patients and often caused by iron deficiency. Anaemia may negatively affect recovery after cardiac surgery. This study aims to determine the efficacy of treatment of postoperative iron deficiency anaemia (IDA) with intravenous iron (IVI) on disability 90 days after cardiac surgery in older patients. Methods: This is a randomized placebo-controlled double blind multi-centre trial. In total, 310 patients aged ≥70 years with moderate IDA on postoperative day 1 (haemoglobin 85 - 110 g/L and ferritin concentration < 100 μg/L or iron saturation <20%) after uncomplicated elective cardiac surgery (aortic valve repair or coronary artery bypass graft surgery) will be included. Patients will be randomly allocated to either receive IVI (ferric derisolmatose) or placebo (sodium chloride 0.9%) on postoperative day 1 in a 1:1 ratio, stratified by centre and type of cardiac surgery. The primary outcome is disability measured by the 12-item World Health Organization Disability Assessment score 2.0 after 90 days. Secondary outcome measures are the number of postoperative red blood cell (RBC) transfusions, change in reticulocyte hemoglobin content (pg) from randomization to hospital discharge, Hb levels at discharge, hospital complications, dyspnoea (assessed with the Rose Dyspnoea Scale) and health-related quality of life (HRQL) (assessed with The Older Persons and Informal Caregivers-Short Form (TOPICS-SF) questionnaire) after 90 days and days alive and out of hospital after 90 days. Lastly, the functional outcomes (e.g. steep ramp or 6-minute walk test) and Hb level after 90 days will be assessed as an exploratory endpoint.Discussion: The results of this study will demonstrate whether early treatment of postoperative IDA with IVI improves disability at 90 days in older cardiac surgery patients. Trial registration: Registered at ClinicalTrials.gov as NCT04913649 at June 4th, 2021.
Gastric Large-cell neuroendocrine carcinoma presenting as Perforation peritonitis: A rare case report
Authors: Aishwarya Ramnath , Jain Ankit , Dutta Souradeep , Abhinaya Reddy , Toi Pampa Ch , Ramakrishnaiah Vishnu Prasad Nelamangala 
Published: August 2022

Abstract
Gastric neuroendocrine carcinomas (GNECs) are rare tumors characterized by an aggressive clinical course, rapid progression, metastatic dissemination, and poor prognosis. Due to overlapping radiological features and small pre-operative biopsy specimens, they are frequently misdiagnosed as adenocarcinoma in the pre-operative period. These tumors are generally asymptomatic or present with non-specific symptoms like epigastric pain or discomfort, weight loss, and loss of appetite. However, GNECs presenting as perforation peritonitis is rarely reported in the literature. A 60-year-old man presented to the emergency department with complaints of pain upper abdomen with loss of weight and appetite for four months. He had an endoscopic biopsy report suggestive of antral growth reported as poorly differentiated adenocarcinoma. Radiological investigations were notable for the presence of a malignant lesion in the stomach with perforation. Subtotal gastrectomy with D1 lymph node resection and Billroth-2 gastrojejunostomy was done. Specimen pathology confirmed poorly differentiated high grade large cell neuroendocrine carcinoma.
Biosorption of heavy metal ions from the aqueous solutions using porous Sargassum Wightii (SW) brown algae: batch adsorption, kinetic and thermodynamic studies
Authors: Yogeshwaran V , Priya A.K 
Published: August 2022

Abstract
The removal of heavy metal ions (Cr, Pb and Zn) present in aqueous solutions has been examined utilizing Sargassum Wightii (SW) - brown algae – as an organic adsorbent. The functional groups of SW were determined by FTIR analysis before and after heavy metal ion adsorption. Because of the strong Van der Walls forces, the SEM/EDX picture reveals the presence of heavy metal ions on the surface of the SW. The influence of adsorption was studied in different settings by adjusting the parameters of pH, SW dosage, metal ion concentration, time of contact and temperature. In addition, the thermodynamic and isotherm investigations were carried out in order to determine the adsorption process and its connection. It was found that by adding 0.3 N H2SO4, the maximal desorption rate was achieved.