bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypermethylation of TMEM240 predicts poor hormone therapy response and disease progression in breast cancer
Authors: Lin Ruo-Kai , Su Chih-Ming , Lin Shih-Yun , Thi Anh Thu Le , Liew Phui-Ly , Chen Jian-Yu , Tzeng Huey-En , Liu Yun-Ru , Chang Tzu-Hao , Lee Cheng-Yang , Hung Chin-Sheng 
Published: June 2022

Abstract
Background
Approximately 25% of patients with early-stage breast cancer experience cancer progression throughout the disease course. Alterations in TMEM240 in breast cancer were identified and investigated to monitor treatment response and disease progression.

Methods
Circulating methylated TMEM240 in the plasma of breast cancer patients was used to monitor treatment response and disease progression. The Cancer Genome Atlas (TCGA) data in Western countries and Illumina methylation arrays in Taiwanese breast cancer patients were used to identify novel hypermethylated CpG sites and genes related to poor hormone therapy response. Quantitative methylation-specific PCR (QMSP), real-time reverse transcription PCR, and immunohistochemical analyses were performed to measure DNA methylation and mRNA and protein expression levels in 394 samples from Taiwanese and Korean breast cancer patients. TMEM240 gene manipulation, viability, migration assays, RNA-seq, and MetaCore were performed to determine its biological functions and relationship to hormone drug treatment response in breast cancer cells.

Results
Aberrant methylated TMEM240 was identified in breast cancer patients with poor hormone therapy response using genome-wide methylation analysis in the Taiwan and TCGA breast cancer cohorts. A cell model showed that TMEM240, which is localized to the cell membrane and cytoplasm, represses breast cancer cell proliferation and migration and regulates the expression levels of enzymes involved in estrone and estradiol metabolism. TMEM240 protein expression was observed in normal breast tissues but was not detected in 88.2% (67/76) of breast tumors and in 90.0% (9/10) of metastatic tumors from breast cancer patients. QMSP revealed that in 54.5% (55/101) of Taiwanese breast cancer patients, the methylation level of TMEM240 was at least twofold higher in tumor tissues than in matched normal breast tissues. Patients with hypermethylation of TMEM240 had poor 10-year overall survival (p = 0.003) and poor treatment response, especially hormone therapy response (p < 0.001). Circulating methylated TMEM240 dramatically and gradually decreased and then diminished in patients without disease progression, whereas it returned and its levels in plasma rose again in patients with disease progression. Prediction of disease progression based on circulating methylated TMEM240 was found to have 87.5% sensitivity, 93.1% specificity, and 90.2% accuracy.

Conclusions
Hypermethylation of TMEM240 is a potential biomarker for treatment response and disease progression monitoring in breast cancer.
Efficient Inverse Method for Structural Identification Considering Modeling and Response Uncertainties
Authors: Cao Lixiong , Liu Jie , Lu Cheng , Wang Wei 
Published: June 2022

AbstractThe inverse problem analysis method provides an effective way for the structural parameter identification. However, uncertainties wildly exist in the practical engineering inverse problems. Due to the coupling of multi-source uncertainties in the measured responses and the modeling parameters, the traditional inverse method under the deterministic framework faces the challenges in solving mechanism and computing cost. In this paper, an uncertain inverse method based on convex model and dimension reduction decomposition is proposed to realize the interval identification of unknown structural parameters according to the uncertain measured responses and modeling parameters. Firstly, the polygonal convex set model is established to quantify the epistemic uncertainties of modeling parameters. Afterwards, a space collocation method based on dimension reduction decomposition is proposed to transform the inverse problem considering multi-source uncertainties into a few interval inverse problems considering response uncertainty. The transformed interval inverse problem involves the two-layer solving process including interval propagation and optimization updating. In order to solve the interval inverse problems considering response uncertainty, an efficient interval inverse method based on the high dimensional model representation and affine algorithm is further developed. Through the coupling of the above two strategies, the proposed uncertain inverse method avoids the time-consuming multi-layer nested calculation procedure, and then effectively realizes the uncertainty identification of unknown structural parameters. Finally, two engineering examples are provided to verify the effectiveness of the proposed uncertain inverse method.
SARS-CoV-2: phenotype, genotype, and characterization of different variants
Authors: Saberiyan Mohammadreza , Karimi Elham , Khademi Zahra , Movahhed Parvaneh , Safi Amir , Mehri-Ghahfarrokhi Ameneh 
Published: June 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), a major international public health concern. Because of very similar amino acid sequences of the seven domain names, SARS-CoV-2 belongs to the Coronavirinae subfamily of the family Coronaviridae, order Nidovirales, and realm Riboviria, placed in exceptional clusters, but categorized as a SARS-like species. As the RNA virus family with the longest genome, the Coronaviridae genome consists of a single strand of positive RNA (25–32 kb in length). Four major structural proteins of this genome include the spike (S), membrane (M), envelope (E), and the nucleocapsid (N) protein, all of which are encoded within the 3′ end of the genome. By engaging with its receptor, angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 infects host cells. According to the most recent epidemiological data, as the illness spread globally, several genetic variations of SARS-CoV-2 appeared quickly, with the World Health Organization (WHO) naming 11 of them. Among these, seven SARS-CoV-2 subtypes have received the most attention. Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.617.2) are now designated as variations of concern (VOC) (B.1.1.529). Lambda (C.37) and Mu are variations of interest (VOI) (B.1.621). The remaining six are either being monitored or are no longer considered a threat. On the basis of studies done so far, antiviral drugs, antibiotics, glucocorticoids, recombinant intravenous immunoglobulin, plasma therapy, and IFN-α2b have been used to treat patients. Moreover, full vaccination is associated with lower infection and helps prevent transmission, but the risk of infection cannot be eliminated completely in vaccinated people.
Parallel and private generalized suffix tree construction and query on genomic data
Authors: Al Aziz Md Momin , Thulasiraman Parimala , Mohammed Noman 
Published: June 2022

Abstract
Background
Several technological advancements and digitization of healthcare data have provided the scientific community with a large quantity of genomic data. Such datasets facilitated a deeper understanding of several diseases and our health in general. Strikingly, these genome datasets require a large storage volume and present technical challenges in retrieving meaningful information. Furthermore, the privacy aspects of genomic data limit access and often hinder timely scientific discovery.

Methods
In this paper, we utilize the Generalized Suffix Tree (GST); their construction and applications have been fairly studied in related areas. The main contribution of this article is the proposal of a privacy-preserving string query execution framework using GSTs and an additional tree-based hashing mechanism. Initially, we start by introducing an efficient GST construction in parallel that is scalable for a large genomic dataset. The secure indexing scheme allows the genomic data in a GST to be outsourced to an untrusted cloud server under encryption. Additionally, the proposed methods can perform several string search operations (i.e., exact, set-maximal matches) securely and efficiently using the outlined framework.

Results
The experimental results on different datasets and parameters in a real cloud environment exhibit the scalability of these methods as they also outperform the state-of-the-art method based on Burrows-Wheeler Transformation (BWT). The proposed method only takes around 36.7s to execute a set-maximal match whereas the BWT-based method takes around 160.85s, providing a 4× speedup.
Sequence-based drug-target affinity prediction using weighted graph neural networks
Authors: Jiang Mingjian , Wang Shuang , Zhang Shugang , Zhou Wei , Zhang Yuanyuan , Li Zhen 
Published: June 2022

Abstract
Background
Affinity prediction between molecule and protein is an important step of virtual screening, which is usually called drug-target affinity (DTA) prediction. Its accuracy directly influences the progress of drug development. Sequence-based drug-target affinity prediction can predict the affinity according to protein sequence, which is fast and can be applied to large datasets. However, due to the lack of protein structure information, the accuracy needs to be improved.

Results
The proposed model which is called WGNN-DTA can be competent in drug-target affinity (DTA) and compound-protein interaction (CPI) prediction tasks. Various experiments are designed to verify the performance of the proposed method in different scenarios, which proves that WGNN-DTA has the advantages of simplicity and high accuracy. Moreover, because it does not need complex steps such as multiple sequence alignment (MSA), it has fast execution speed, and can be suitable for the screening of large databases.

Conclusion
We construct protein and molecular graphs through sequence and SMILES that can effectively reflect their structures. To utilize the detail contact information of protein, graph neural network is used to extract features and predict the binding affinity based on the graphs, which is called weighted graph neural networks drug-target affinity predictor (WGNN-DTA). The proposed method has the advantages of simplicity and high accuracy.
Conversion between duplicated genes generated by polyploidization contributes to the divergence of poplar and willow
Authors: Wang Jianyu , Zhang Lan , Wang Jiaqi , Hao Yanan , Xiao Qimeng , Teng Jia , Shen Shaoqi , Zhang Yan , Feng Yishan , Bao Shoutong , Li Yu , Yan Zimo , Wei Chendan , Wang Li , Wang Jinpeng 
Published: June 2022

Abstract
Background
Gene conversion has an important effect on duplicate genes produced by polyploidization. Poplar (Populus trichocarpa) and willow (Salix brachista) are leading models and excellent green plants in the Salicaceae. Although much attention has been paid to the evolution of duplicated genes in poplar and willow, the role of conversion between duplicates generated from polyploidization remains poorly understood.

Results
Here, through genomic synteny analyses, we identified duplicate genes generated by the Salicaceae common tetraploidization (SCT) in the poplar and willow genomes. We estimated that at least 0.58% and 0.25% of poplar and willow duplicates were affected by whole-gene conversion after the poplar-willow divergence, with more (5.73% and 2.66%) affected by partial-gene conversion. Moreover, we found that the converted duplicated genes were unevenly distributed on each chromosome in the two genomes, and the well-preserved homoeologous chromosome regions may facilitate the conversion of duplicates. Notably, we found that conversion maintained the similarity of duplicates, likely contributing to the conservation of certain sequences, but is essentially accelerated the rate of evolution and increased species divergence. In addition, we found that converted duplicates tended to have more similar expression patterns than nonconverted duplicates. We found that genes associated with multigene families were preferentially converted. We also found that the genes encoding conserved structural domains associated with specific traits exhibited a high frequency of conversion.

Conclusions
Extensive conversion between duplicate genes generated from the SCT contributes to the diversification of the family Salicaceae and has had long-lasting effects on those genes with important biological functions.
Identifying Potential Factors Associated with High HIV viral load in KwaZulu-Natal, South Africa using Multiple Correspondence Analysis and Random Forest Analysis
Authors: Soogun Adenike O. , Kharsany Ayesha B. M. , Zewotir Temesgen , North Delia , Ogunsakin Ropo Ebenezer 
Published: June 2022

Abstract
Background
Sustainable Human Immunodeficiency Virus (HIV) virological suppression is crucial to achieving the Joint United Nations Programme of HIV/AIDS (UNAIDS) 95–95-95 treatment targets to reduce the risk of onward HIV transmission. Exploratory data analysis is an integral part of statistical analysis which aids variable selection from complex survey data for further confirmatory analysis.

Methods
In this study, we divulge participants’ epidemiological and biological factors with high HIV RNA viral load (HHVL) from an HIV Incidence Provincial Surveillance System (HIPSS) sequential cross-sectional survey between 2014 and 2015 KwaZulu-Natal, South Africa. Using multiple correspondence analysis (MCA) and random forest analysis (RFA), we analyzed the linkage between socio-demographic, behavioral, psycho-social, and biological factors associated with HHVL, defined as ≥400 copies per m/L.

Results
Out of 3956 in 2014 and 3868 in 2015, 50.1% and 41% of participants, respectively, had HHVL. MCA and RFA revealed that knowledge of HIV status, ART use, ARV dosage, current CD4 cell count, perceived risk of contracting HIV, number of lifetime HIV tests, number of lifetime sex partners, and ever diagnosed with TB were consistent potential factors identified to be associated with high HIV viral load in the 2014 and 2015 surveys. Based on MCA findings, diverse categories of variables identified with HHVL were, did not know HIV status, not on ART, on multiple dosages of ARV, with less likely perceived risk of contracting HIV and having two or more lifetime sexual partners.

Conclusion
The high proportion of individuals with HHVL suggests that the UNAIDS 95–95-95 goal of HIV viral suppression is less likely to be achieved. Based on performance and visualization evaluation, MCA was selected as the best and essential exploration tool for identifying and understanding categorical variables’ significant associations and interactions to enhance individual epidemiological understanding of high HIV viral load. When faced with complex survey data and challenges of variables selection in research, exploratory data analysis with robust graphical visualization and reliability that can reveal divers’ structures should be considered.
Benzydamine hydrochloride for the treatment of sore throat and irritative/inflammatory conditions of the oropharynx: a cross-national survey among pharmacists and general practitioners
Authors: Passali Desiderio , Arezzo Maria Felice , De Rose Alessandra , De Simone Gianmarco , Forte Gianluigi , Jablko-Musial Michalina , Mösges Ralph 
Published: June 2022

Abstract
Background
Benzydamine for oromucosal use is indicated in the relief of pain and irritation of the mouth and throat. It is an indazole derivative, non-steroidal anti-inflammatory drug, with combined local anesthetic and analgesic properties, and antiseptic activity, marketed under the brand name “Tantum Verde”. The aim of this study was to explore knowledge and prescriptive/advising attitudes among general practitioners (GPs) and pharmacists (PHs) with regard to the topical treatment of sore throat and other irritative/inflammatory conditions of the oropharynx, with a focus on benzydamine. These findings could be important to increase awareness on benzydamine efficacy in sore throat and stomatological conditions, and to reinforce knowledge on the characteristics of benzydamine and its mechanisms of action among healthcare professionals (pediatricians, otolaryngologists, oncologists, etc.).

Materials and methods
An online questionnaire survey was performed among PHs and GPs in four European countries (Italy, Germany, Russia and Poland).

Results
Both GPs and PHs proved to have an excellent knowledge and mastery of the constituents effective against oral symptoms. Among all the principles, benzydamine hydrochloride is the most recognized as certainly suitable for the topical treatment of sore throat symptoms and various inflammatory/irritative conditions of the oral cavity. It is recommended by about 90% of PHs and prescribed by 80% of GPs, mainly to solve the ailments caused by sore throats and stomatitis, especially for its anti-inflammatory, analgesic and anesthetic characteristics. Also in the pediatric field, benzydamine hydrochloride is recommended: among GPs, a high percentage (about 40%) prescribes it like the remedies based on dichlorobenzyl alcohol-sodium benzoate, which are instead more often recommended by PHs (44% against 37%).

Conclusion
Although the public has a lot of confidence in this treatment, GPs and PHs do not recommend/prescribe benzydamine as a first-line treatment of sore throat and other irritative/inflammatory conditions of the oropharynx. To increase the knowledge of benzydamine among these healthcare professionals, it would be important to emphasize its characteristics and the different irritative/inflammatory conditions of the oropharynx in which it can be used.
Impact of septic cerebral embolism on prognosis and therapeutic strategies of infective endocarditis: a retrospective study in a surgical centre
Authors: Scheggi Valentina , Menale Silvia , Tonietti Barbara , Bigiarini Costanza , Giovacchini Jacopo , Del Pace Stefano , Zoppetti Nicola , Alterini Bruno , Stefàno Pier Luigi , Marchionni Niccolò 
Published: June 2022

Abstract
Background
Infective endocarditis still has high mortality and invalidating complications, such as cerebral embolism. The best strategies to prevent and manage neurologic complications remain uncertain. This study aimed to identify predictors of cerebral septic embolism and evaluate the role of surgery in these patients in a real-world surgical centre.

Methods
We retrospectively analyzed 551 consecutive patients admitted to our department with a definite diagnosis of non-device-related infective endocarditis; of these, 126 (23%) presented a neurologic complication.

Results
Cerebral embolism was significantly more frequent in patients with large vegetations (p = 0.004), mitral valve infection (p = 0.001), and Staphylococcus aureus infection (p = 0.025). At multivariable analysis, only vegetation length was an independent predictor of cerebral embolism (HR per unit 1.057, 95% CI 1.025–1.091, p 0.001), with a best predictive threshold of 10 mm at ROC curve analysis (AUC 0.54, p = 0.001). Patients with neurologic complications were more often excluded from surgery despite an indication to it (16% vs 8%, p = 0.001). If eligible, they were treated within two weeks from diagnosis in similar proportions as patients without cerebral embolism with a similar survival rate. Predictors of mortality were hemorrhagic lesions (p = 0.018), a GCS < 14 (p = 0.001) or a severe degree of disability (p = 0.001) at presentation. The latter was the only independent predictor of mortality at multivariable analysis (HR 2.3, 95% CI 1.43–3.80, p = 0.001).

Conclusions
The present study highlights the prognostic value of functional presentation and the safety of cardiac surgery, when feasible, in patients with cerebral septic embolism.
Prevalence of pruritus associated with hemodialysis and its association with sleep quality among hemodialysis patients: a multicenter study
Authors: Daraghmeh Mefleh , Badran Montaser , Janajreh Ahmad , Hassan Mohanad , Taha Adham Abu , Koni Amer A. , Zyoud Sa’ed H. 
Published: June 2022

Abstract
Background
CKD-associated pruritus (chronic kidney disease-associated pruritus) is one of the common symptoms in hemodialysis patients, with a major effect on sleep quality because it occurs at night. The main objective of this study is to determine the prevalence of pruritus among hemodialysis (HD) patients and its impact on sleep and investigate factors associated with pruritus and sleep quality.

Methods
A cross-sectional study began in January until March of 2021 in HD centers of four different hospitals in the West Bank, Palestine. Patients with HD aged 18 years or older were included in our investigation. Pruritus and sleep problems were assessed by a 5-D itching score and the Pittsburgh Sleep Quality Index (PSQI) score.

Results
Of 280 HD patients, 250 were accepted to participate in our study. The mean age of the participants was (54.9 ± 15.08). 62.8% were male, and 42.4% of the participants were elderly (age ≥ 60yrs). Pruritus was observed in 121 (48.4%). The 5-D itching score had a median [IQR] of 5.0[5.0–15.0], and 57.2% had a score ≥ 6 points. Severe pruritus was reported in 28.1% of patients. The score was significantly associated with residency (p = 0.033) and chronic comorbidities (p = 0.026). The PSQI score has a median [IQR] of 8[5–12], and 66.4% are poor sleepers with a score of < 5. The score was significantly associated with age (p = 0.017), marital status (p = 0.022), occupational status (p = 0.007), chronic comorbidities (p > 0.001), chronic medication (p = 0.008), severity of pruritus (p = 0.003) and duration of pruritus (p = 0.003). Regression analysis showed that the 5-D itching score and the total number of comorbidities were significantly associated with the PSQI score.

Conclusions
Pruritus is a widespread complication among HD patients in Palestine. Pruritus also has major effects on sleep quality and is associated with poor sleep quality.
Case report: the management for a gestational hypertensive woman with influenza A virus pneumonia and peripartum cardiomyopathy
Authors: Ng Kwok-On , Chow Lok-Hi , Yeh Chun-Chang , Huang Eagle Yi-Kung , Liu Wei-Cheng , Tan Ping-Heng 
Published: June 2022

Abstract
Background
Peripartum cardiomyopathy (PPCM) is defined as an idiopathic cardiomyopathy occurring in the last month of pregnancy or the first 6 months postpartum without an identifiable cause. PPCM is suspected to be triggered by the generation of a cardiotoxic fragment of prolactin and the secretion of a potent antiangiogenic protein from the placental, but no single factor has been identified or defined as the underlying cause of the disease. Influenza virus can cause PPCM through immune-mediated response induced by proinflammatory cytokines from host immunity and endothelial cell dysfunction. We report a case in a parturient woman undergoing a cesarean delivery, who had influenza A pneumonia and PPCM.

Case presentation
A parturient woman at 40 weeks and 1 day of gestation who had experienced gestational hypertension accompanied by pulmonary edema developed hypotension after undergoing an emergency cesarean delivery. An elevation of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was noted, and echocardiography revealed a left ventricular ejection fraction of 20%. She underwent a nasopharyngeal swab test, in which influenza A antigen was positive. She was diagnosed as having PPCM and received anti-viral treatment. After antiviral treatment, hemodynamic dysfunction stabilized. We present and discuss the details of this event.

Conclusion
PPCM is a heart disease that is often overlooked by medical personnel. Rapid swab tests, serum creatine kinase measurement, and echocardiography are imperative diagnostic approaches for the timely recognition of virus-associated cardiomyopathy in peripartum women with influenza-like disease and worsening dyspnea, especially during the epidemic season. Prompt antiviral treatment should be considered, particularly after PPCM is diagnosed.