bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2-low breast cancer: evolution of HER2 expression from primary tumor to distant metastases
Authors: Cai Mengyuan , Li Ming , Lv Hong , Zhou Shuling , Xu Xiaoli , Shui Ruohong , Yang Wentao 
Published: July 2023

Abstract
Background
Breast cancer (BC) with low human epidermal growth factor receptor 2 (HER2) expression is attracting much attention due to the breakthrough progress of novel anti-HER2 antibody-drug conjugates. HER2 expression is examined in patients with HER2-low BC and their distant metastases in this study, so as to further clarify the dynamic characteristics of HER2 low status in the process of disease progression.

Methods
Patients diagnosed with HER2 low breast cancer (defined as IHC1+ or IHC2+/ISH-) between 2012 and 2021 were included in this study. We evaluated HER2 expression of primary sites and metastatic sites, compared the impact of different clinicopathological parameters on HER2 status of metastases and compared the overall survival and disease-free survival of patients with different HER2 status in metastases.

Results
Ninety-eight patients were included. All HER2 IHC scores were confirmed and the consistent rate with the original pathological report was 81.1%. 27.6% of the patients showed different HER2 status in metastases. The HER2 discordance rate differed among different metastatic sites (p = 0.040). The higher the T stage of the primary BC, the higher the rate of HER2 discordance was observed (p = 0.042). For the specimen type of metastasis, HER2 discordant rate was higher in surgical specimen than biopsy (p = 0.050). No difference of HER2 discordance rate was found between HER2-1+ and HER2-2+ patients. But comparing HER2 IHC score, HER2-2+ patients were less likely to have consistent metastatic HER2 levels than HER2-1+ patients (p = 0.006). No difference in survival outcomes was observed between patients with different HER2 status in metastases.

Conclusions
There is a possibility of HER2 expression alteration in the metastases of HER2-low breast cancer. And the rate of altered HER2 low expression was different among different metastatic sites, different T stages of primary BC and specimen type of metastasis. No prognostic significance was observed.
Management of metastatic melanoma in Texas: disparities in the utilization of immunotherapy following the regulatory approval of immune checkpoint inhibitors
Authors: Olateju Olajumoke A. , Zeng Zhen , Thornton J. Douglas , Mgbere Osaro , Essien Ekere James 
Published: July 2023

Abstract
Background
The utilization of modern-immunotherapies, notably immune checkpoint inhibitors (ICIs), has increased markedly in patients with metastatic melanoma over the past decade and are recommended as standard treatment. Given their increasing adoption in routine care for melanoma, understanding patient access to immunotherapy and patterns of its use in Texas is crucial as it remains one of the few states without Medicaid expansion and with high rates of the uninsured population. The objectives of this study were to examine the trend in the utilization of immunotherapy and to determine factors associated with immunotherapy utilization among patients with metastatic melanoma in the era of ICIs in Texas.

Methods
A retrospective cohort study was conducted using the Texas Cancer Registry (TCR) database. The cohort comprised of adult (≥ 18 years) patients with metastatic melanoma diagnosed between June 2011 and December 2018. The trend in immunotherapy utilization was assessed by determining the proportion of patients receiving immunotherapy each year. The Average Annual Percent Change (AAPC) in immunotherapy utilization was assessed using joinpoint regression, while multivariable logistic regression was used to determine the association between patient characteristics and immunotherapy receipt.

Results
A total of 1,795 adult patients with metastatic melanoma were identified from the TCR. Immunotherapy utilization was higher among younger patients, those with no comorbidities, and patients with private insurance. Multivariable analysis showed that the likelihood of receipt of immunotherapy decreased with older age [(adjusted Odds Ratio (aOR), 0.92; 95% CI, 0.89– 0.93, p = 0.001], living in high poverty neighborhood (aOR, 0.52; 95% CI, 0.44 – 0.66, p < 0.0001), having Medicaid (aOR, 0.58; 95% CI, 0.44 – 0.73, p = 0.02), being uninsured (aOR, 0.49; 95% CI, 0.31 – 0.64, p = 0.01), and having comorbidities (CCI score 1: aOR, 0.48; 95% CI, 0.34 – 0.71, p = 0.003; CCI score ≥ 2: aOR, 0.32; 95% CI, 0.16 – 0.56, p < 0.0001).

Conclusions and relevance
This cohort study identified sociodemographic and socioeconomic disparities in access to immunotherapy in Texas, highlighting the need for policies such as Medicaid expansion that would increase equitable access to this innovative therapy.
Parents’ self-reporting of Child Physical Maltreatment (CPM) in a low-middle-income country
Authors: Abdeen Mai SeifElDin , Hashim Mostafa Ahmad , Ghanem Marwa Mohamed , El-Din Nouran Yousef Salah , Nagar Zeinab Mohamed El 
Published: July 2023

Abstract
Background
Because of COVID-19 pandemic, families across the world are experiencing new stressors that threaten their health, and economic well-being. Such a stress may jeopardize parents-children relationship. We aim to investigate the magnitude of child physical maltreatment (CPM) by parents in Egypt during the COVID-19 pandemic, to relate it to parents’ stress, and to identify other potential risk factors.

Methods
This cross-sectional study assessed parent-reported CPM and their personal experience of stress, depression, and anxiety among a sample of Egyptian parents using an electronic survey. It included sociodemographic data, Depression, Anxiety and Stress Scale (DASS-21), and the Child physical maltreatment scale (CPMS). We also briefly assessed COVID-19 -related data.

Results
Out of 404 respondents, (62.9%) and (32.9%) reported performing minor and severe CPM toward their children during the past 3 months, respectively. The age of youngest child, and anxiety score were significantly correlated with both minor and severe forms of CPM. While number of children, and online education system ratings were only significantly correlated with severe CPM. Parental definition of CPM was significantly correlated to minor CPM, but not to severe CPM.

Conclusions
CPM by parents is not uncommon in Egypt, especially during the COVID-19 pandemic. These findings highlight the importance of regular support and intervention that help parents learn parenting skills and the use of non-violent child disciplining methods.
Exergames improves cognitive functions in adolescents with depression: study protocol of a prospective, assessor-blind, randomized controlled trial
Authors: Wang De-Quan , Zhang Jing-Jing , Chen Jian-Ning , Li Ren-Yu , Luo Yi-Xiang , Deng Wei 
Published: July 2023

Abstract
Background
Depression is a condition that imposes a significant disease burden, with cognitive impairment being one of its costly symptoms. While cognitive rehabilitation is crucial, it is also challenging. Although some studies have investigated the impact of exergames on cognitive function improvement, these have primarily focused on the elderly population, with limited attention given to individuals with depression. Consequently, this study aims to investigate the effects of exergames on cognitive functions in adolescents with depression and compare the effectiveness of exergames with traditional exercise.

Method
The present investigation is a single-center randomized controlled trial that employs the ANOVA method to calculate the sample size using G*Power software, assuming a 25% dropout rate. The study enrolls fifty-four eligible patients with depression who are randomly allocated to one of three treatment groups: the exergames group, which receives standard treatment and exergames intervention; the exercise group, which receives standard treatment and traditional exercise intervention; and the control group, which receives standard treatment exclusively. The study provides a comprehensive regimen of 22 supervised exercise and exergame sessions over an 8-week period, with a frequency of twice per week for the initial two weeks and three times per week for the subsequent six weeks. The researchers gather cognitive, mood, and sleep metrics at the onset of the first week, as well as at the conclusion of the fourth and eighth weeks. The researchers employ a wearable device to track participants' heart rate during each intervention session and evaluate the Borg Rating of Perceived Exertion scale at the conclusion of each session.

Discussion
The findings from this study make several contributions to the current literature. First, this study comprehensively reports the efficacy of an exergames intervention for multidimensional symptoms in adolescents with depression. Second, this study also compares the efficacy of exergames with that of traditional exercise. These findings provide a theoretical basis for the use of exergames as an adjunctive intervention for depression and lay the groundwork for future research.

Trial registration
This trial is registered with the Chinese Clinical Trials Registry (Registration number: ChiCTR2100052709; Registration Status: Prospective registration;) 3/11/2021, URL: http://www.chictr.org.cn/edit.aspx?pid=135663&htm=4.
Hybridisation has shaped a recent radiation of grass-feeding aphids
Authors: Mathers Thomas C. , Wouters Roland H. M. , Mugford Sam T. , Biello Roberto , van Oosterhout Cock , Hogenhout Saskia A. 
Published: July 2023

Abstract
Background
Aphids are common crop pests. These insects reproduce by facultative parthenogenesis involving several rounds of clonal reproduction interspersed with an occasional sexual cycle. Furthermore, clonal aphids give birth to live young that are already pregnant. These qualities enable rapid population growth and have facilitated the colonisation of crops globally. In several cases, so-called “super clones” have come to dominate agricultural systems. However, the extent to which the sexual stage of the aphid life cycle has shaped global pest populations has remained unclear, as have the origins of successful lineages. Here, we used chromosome-scale genome assemblies to disentangle the evolution of two global pests of cereals—the English (Sitobion avenae) and Indian (Sitobion miscanthi) grain aphids.

Results
Genome-wide divergence between S. avenae and S. miscanthi is low. Moreover, comparison of haplotype-resolved assemblies revealed that the S. miscanthi isolate used for genome sequencing is likely a hybrid, with one of its diploid genome copies closely related to S. avenae (~ 0.5% divergence) and the other substantially more divergent (> 1%). Population genomics analyses of UK and China grain aphids showed that S. avenae and S. miscanthi are part of a cryptic species complex with many highly differentiated lineages that predate the origins of agriculture. The complex consists of hybrid lineages that display a tangled history of hybridisation and genetic introgression.

Conclusions
Our analyses reveal that hybridisation has substantially contributed to grain aphid diversity, and hence, to the evolutionary potential of this important pest species. Furthermore, we propose that aphids are particularly well placed to exploit hybridisation events via the rapid propagation of live-born “frozen hybrids” via asexual reproduction, increasing the likelihood of hybrid lineage formation.
Targeted inhibition of PTPN22 is a novel approach to alleviate osteogenic responses in aortic valve interstitial cells and aortic valve lesions in mice
Authors: Li Shunyi , Luo Zichao , Su Shuwen , Wen Liming , Xian Gaopeng , Zhao Jing , Xu Xingbo , Xu Dingli , Zeng Qingchun 
Published: July 2023

Abstract
Background
Calcific aortic valve disease (CAVD) is the most prevalent valvular disease and has high morbidity and mortality. CAVD is characterized by complex pathophysiological processes, including inflammation-induced osteoblastic differentiation in aortic valve interstitial cells (AVICs). Novel anti-CAVD agents are urgently needed. Protein tyrosine phosphatase nonreceptor type 22 (PTPN22), an intracellular nonreceptor-like protein tyrosine phosphatase, is involved in several chronic inflammatory diseases, including rheumatoid arthritis and diabetes. However, it is unclear whether PTPN22 is involved in the pathogenesis of CAVD.

Methods
We obtained the aortic valve tissue from human and cultured AVICs from aortic valve. We established CAVD mice model by wire injury. Transcriptome sequencing, western bolt, qPCR, and immunofluorescence were performed to elucidate the molecular mechanisms.

Results
Here, we determined that PTPN22 expression was upregulated in calcific aortic valve tissue, AVICs treated with osteogenic medium, and a mouse model of CAVD. In vitro, overexpression of PTPN22 induced osteogenic responses, whereas siRNA-mediated PTPN22 knockdown abolished osteogenic responses and mitochondrial stress in the presence of osteogenic medium. In vivo, PTPN22 ablation ameliorated aortic valve lesions in a wire injury-induced CAVD mouse model, validating the pathogenic role of PTPN22 in CAVD. Additionally, we discovered a novel compound, 13-hydroxypiericidin A 10-O-α-D-glucose (1 → 6)-β-D-glucoside (S18), in a marine-derived Streptomyces strain that bound to PTPN22 with high affinity and acted as a novel inhibitor. Incubation with S18 suppressed osteogenic responses and mitochondrial stress in human AVICs induced by osteogenic medium. In mice with aortic valve injury, S18 administration markedly alleviated aortic valve lesions.

Conclusion
PTPN22 plays an essential role in the progression of CAVD, and inhibition of PTPN22 with S18 is a novel option for the further development of potent anti-CAVD drugs.

Graphical Abstract
Therapeutic inhibition of PTPN22 retards aortic valve calcification through modulating mitochondrial dysfunction in AVICs.
Left atrioventricular interaction and impaired left atrial phasic function in type 2 diabetes mellitus patients with or without anemia: a cardiac magnetic resonance study
Authors: Qian Wen-Lei , Yang Zhi-Gang , Shi Rui , Guo Ying-Kun , Fang Han , Shen Meng-ting , Li Yuan 
Published: July 2023

Abstract
Objective
Type 2 diabetes mellitus (T2DM) and anemia are related to some cardiovascular diseases and can predict poor outcomes. Both of them can damage the heart in their own ways, but their combined effects have not been well explored. This study aimed to explore the combined effects of T2DM and anemia and the interaction between left atrial (LA) and left ventricular (LV) function by cardiac magnetic resonance (CMR).

Materials and methods
A total of 177 T2DM patients without anemia, 68 T2DM patients with anemia and 73 sex-matched controls were retrospectively enrolled in this study from June 2015 to September 2022. Their LA phasic function and LV function parameters were compared to explore the combined effects of T2DM and anemia and the interaction between LA and LV function. Univariate and multivariate linear regression were done to explore the independent factors influencing LA phasic function and LV function.

Results
Compared with controls and T2DM patients without anemia, T2DM patients with anemia were older and had higher heart rate, higher creatinine, lower estimated glomerular filtration rate (eGFR) and lower hemoglobin (Hb) (all p < 0.05). LV global longitudinal peak strain (GLPS) significantly declined from T2DM patients with anemia to T2DM patients without anemia to controls (p < 0.001). LA volumetric function and strain were significantly impaired in T2DM patients with anemia compared with the other groups (all p < 0.05). In addition to age, eGFR, Hb and HbA1c, the LV GLPS was independently associated with all LA phasic strains (LA reservoir strain, β =0.465; LA conduit strain, β = 0.450; LA pump strain, β = 0.360, all p < 0.05). LA global conduit strain, total LA ejection fraction (LAEF) and active LAEF were independently associated with LV GLPS and LVEF.

Conclusion
Both LA and LV function were severely impaired in T2DM patients with anemia, and T2DM and anemia were independently associated with LA phasic function. Deleterious interaction between LA function and LV function would happen in T2DM patients with or without anemia. Timely and effective monitoring and management of both LA and LV function will benefit T2DM patients.
A three-snoRNA signature: SNORD15A, SNORD35B and SNORD60 as novel biomarker for renal cell carcinoma
Authors: Zhang Yue , Shang Xiaoling , Yu Miao , Bi Zhao , Wang Kangyu , Zhang Qianru , Xie Li , Song Xianrang , Song Xingguo 
Published: July 2023

Abstract
Background
Accumulating evidence has confirmed the role of snoRNAs in a variety of cancer, but rare in renal cell carcinoma (RCC). This study aims to clarify the role of snoRNAs in RCC tumorigenesis and their potential as novel tumor biomarkers.

Materials and methods
The snoRNA expression matrix was obtained from the public TCGA and SNORic databases. SNORD15A, SNORD35B and SNORD60 were selected and validated by qPCR, then analyzed combined with related clinical factors using T-test and ROC curve.

Results
All three snoRNAs: SNORD15A, SNORD35B and SNORD60 were significantly upregulated in cancer tissues compared to adjacent tissues from TCGA or FFPE detection. These three snoRNAs were also increased in urinary sediment (US) of RCC as well as the early-stage RCC patients compared with the healthy controls. In addition, RNase stability experiments confirmed their stable existence in US. Meanwhile, the ROC curve shows that SNORD15A, SNORD35B and SNORD60 could effectively distinguish RCC (AUC = 0.7421) and early-stage RCC (AUC = 0.7465) from healthy individuals.

Conclusion
SNORD15A, SNORD35B and SNORD60 were upregulated in tissues and US of RCC, serving as novel potential biomarkers for RCC diagnosis.
A precise molecular subtyping of ulcerative colitis reveals the immune heterogeneity and predicts clinical drug responses
Authors: Mo Shaocong , Jin Bryan , Tseng Yujen , Lin Lingxi , Lin Lishuang , Shen Xin , Song Huan , Kong Mingjia , Luo Zhongguang , Chu Yiwei , Jiang Chen , Cao Zhiwei , Liu Jie , Luo Feifei 
Published: July 2023

Abstract
Background and Aims
We sought to identify novel molecular subtypes of ulcerative colitis (UC) based on large-scale cohorts and establish a clinically applicable subtyping system for the precision treatment of the disease.

Methods
Eight microarray profiles containing colon samples from 357 patients were utilized. Expression heterogeneity was screened out and stable subtypes were identified among UC patients. Immune infiltration pattern and biological agent response were compared among subtypes to assess the value in guiding treatment. The relationship between PRLR and TNFSF13B genes with the highest predictive value was further validated by functional experiments.

Results
Three stable molecular subtypes were successfully identified. Immune cell infiltration analysis defined three subtypes as innate immune activated UC (IIA), whole immune activated UC (WIA), and immune homeostasis like UC (IHL). Notably, the response rate towards biological agents (infliximab/vedolizumab) in WIA patients was the lowest (less than 10%), while the response rate in IHL patients was the highest, ranging from 42 to 60%. Among the featured genes of subtypes, the ratio of PRLR to TNFSF13B could effectively screen for IHL UC subtype suitable for biological agent therapies (Area under curve: 0.961–0.986). Furthermore, we demonstrated that PRLR expressed in epithelial cells could inhibit the expression of TNFSF13B in monocyte-derived macrophages through the CXCL1-NF-κB pathway.

Conclusions
We identified three stable UC subtypes with a heterogeneous immune pattern and different response rates towards biological agents for the first time. We also established a precise molecular subtyping system and classifier to predict clinical drug response and provide individualized treatment strategies for UC patients.
Screening and identification of emodin as an EBV DNase inhibitor to prevent its biological functions
Authors: Wu Chung-Chun , Chen Mei-Shu , Lee Ting-Ying , Cheng Yu-Jhen , Tsou Hsiao-Hui , Huang Tze-Sing , Cho Der-Yang , Chen Jen-Yang 
Published: July 2023

Abstract
Background
The Epstein-Barr virus (EBV) is a prevalent oncovirus associated with a variety of human illnesses. BGLF5, an EBV DNase with alkaline nuclease (AN) activity, plays important roles in the viral life cycle and progression of human malignancies and has been suggested as a possible diagnostic marker and target for cancer therapy. Methods used conventionally for the detection of AN activity, radioactivity-based nuclease activity assay and DNA digestion detection by gel electrophoresis, are not suitable for screening AN inhibitors; the former approach is unsafe, and the latter is complicated. In the present study, a fluorescence-based nuclease activity assay was used to screen several natural compounds and identify an EBV DNase inhibitor.

Results
Fluorescence-based nuclease activity assays, in which the DNA substrate is labelled with PicoGreen dye, are cheaper, safer, and easier to perform. Herein, the results of the fluorescence-based nuclease activity assay were consistent with the results of the two conventional methods. In addition, the PicoGreen-labelling method was applied for the biochemical characterisation of viral nucleases. Using this approach, we explored EBV DNase inhibitors. After several rounds of screening, emodin, an anthraquinone derivative, was found to possess significant anti-EBV DNase activity. We verified the efficacy of emodin using the conventional DNA-cleavage assay. Furthermore, using comet assay and micronucleus formation detection, we confirmed that emodin can inhibit DNase-induced DNA damage and genomic instability. Additionally, emodin treatment inhibited EBV production.

Conclusions
Using a PicoGreen-mediated nuclease activity assay, we successfully demonstrated that emodin has the potential to inhibit EBV DNase nuclease activity. Emodin also inhibits EBV DNase-related biological functions, suggesting that it is a potential inhibitor of EBV DNase.
Circulation of multiple hepatitis B virus genotypes in individual pregnant women seeking antenatal care in northern Ghana
Authors: Anabire Nsoh Godwin , Quaye Osbourne , Helegbe Gideon Kofi 
Published: July 2023

Abstract
Background
Identification and monitoring of HBV genotype variations is important, since that can help forecast the likelihood of developing serious liver disease and how well patients respond to antiviral medication. Given that HBV genotyping tests are not widely available in our healthcare system, this study characterized HBV genotypes in pregnant women seeking prenatal treatment in northern Ghana.

Method
By a cross-sectional approach, 2071 pregnant women seeking antenatal care in health facilities in northern Ghana were screened for HBV infection using hepatitis B surface antigen (HBsAg) rapid diagnostic test kit. The women were aged between 17 and 41 years, were of varying gravidae (primigravidae and multigravidae) and gestational age (first, second and third trimesters). A confirmatory PCR assay was used to detect HBsAg, and the distribution of HBV genotypes was determined using a nested PCR assay.

Results
Three HBV genotypes (A, D and E) were detected among the pregnant women, of which 175 (91.6%) had genotype E, 9 (4.7%) had mixed genotypes A and E, 5 (2.6%) had mixed genotypes D and E, and 2 (1.1) had mixed genotypes A, D and E. The proportions of women with the different HBV genotypes were independent of age (p = 0.925), gravidity (p = 0.193, χ2 = 4.729) and gestational age (p = 0.227, χ2 = 8.152).

Conclusion
This study for the first-time characterized circulating HBV genotypes in pregnant women in northern Ghana, which reveals genotypes A and D are found in mixed infections with genotype E. The findings have clinical implications on the management of chronic HBV infection among pregnant women in northern Ghana.