bluuebunny/crossref_metadata_2025_split huggingface dataset:
ROS1-mediated decrease in DNA methylation and increase in expression of defense genes and stress response genes in Arabidopsis thaliana due to abiotic stresses
Authors: Yang Liping , Lang Chenjing , Wu Yanju , Meng Dawei , Yang Tianbo , Li Danqi , Jin Taicheng , Zhou Xiaofu 
Published: March 2022

Abstract
Background
Small interfering RNAs (siRNAs) target homologous genomic DNA sequences for cytosine methylation, known as RNA-directed DNA methylation (RdDM), plays an important role in transposon control and regulation of gene expression in plants. Repressor of silencing 1 (ROS1) can negatively regulate the RdDM pathway.

Results
In this paper, we investigated the molecular mechanisms by which an upstream regulator ACD6 in the salicylic acid (SA) defense pathway, an ABA pathway-related gene ACO3, and GSTF14, an endogenous gene of the glutathione S-transferase superfamily, were induced by various abiotic stresses. The results demonstrated that abiotic stresses, including water deficit, cold, and salt stresses, induced demethylation of the repeats in the promoters of ACD6, ACO3, and GSTF14 and transcriptionally activated their expression. Furthermore, our results revealed that ROS1-mediated DNA demethylation plays an important role in the process of transcriptional activation of ACD6 and GSTF14 when Arabidopsis plants are subjected to cold stress.

Conclusions
This study revealed that ROS1 plays an important role in the molecular mechanisms associated with genes involved in defense pathways in response to abiotic stresses.
Are gastrointestinal symptoms associated with higher risk of Mortality in COVID-19 patients? A systematic review and meta-analysis
Authors: Wang Yang , Li Yimin , Zhang Yifan , Liu Yun , Liu  Yulan 
Published: March 2022

AbstractBackgroundGastrointestinal symptoms have been reported in patients with COVID-19. Several clinical investigations suggested that gastrointestinal symptoms were associated with disease severity of COVID-19. However, the relevance of gastrointestinal symptoms and mortality of COVID-19 remains largely unknown. We aim to investigate the relationship between gastrointestinal symptoms and COVID-19 mortality.MethodsWe searched the PubMed, Embase, Web of science and Cochrane for studies published between Dec 1, 2019 and May 1, 2021, that had data on gastrointestinal symptoms in COVID-19 patients. Additional literatures were obtained by screening the citations of included studies and recent reviews. Only studies that reported the mortality of COVID-19 patients with/without gastrointestinal symptoms were included. Raw data were pooled to calculate OR (Odds Ratio). The mortality was compared between patients with and without gastrointestinal symptoms, as well as between patients with and without individual symptoms (diarrhea, nausea/vomiting, abdominal pain).ResultsFifty-three literatures with 55,245 COVID-19 patients (4955 non-survivors and 50,290 survivors) were included. The presence of GI symptoms was not associated with the mortality of COVID-19 patients (OR=0.88; 95% CI 0.71–1.09;P=0.23). As for individual symptoms, diarrhea (OR=1.01; 95% CI 0.72–1.41;P=0.96), nausea/vomiting (OR=1.16; 95% CI 0.78–1.71;P=0.46) and abdominal pain (OR=1.55; 95% CI 0.68–3.54;P=0.3) also showed non-relevance with the death of COVID-19 patients.ConclusionsGastrointestinal symptoms are not associated with higher mortality of COVID-19 patients. The prognostic value of gastrointestinal symptoms in COVID-19 requires further investigation.
Long-term survival of a patient with liver metastases from clear cell gastric adenocarcinoma after multimodality treatment including interventional oncology techniques: case report
Authors: Jugovec Vesna , Benedik Jernej , Jeruc Jera , Popovic Peter 
Published: March 2022

Abstract
Background
Gastric cancer (GC) is the fourth most common cancer and the third leading cancer-related cause of death worldwide since most patients are diagnosed at an advanced stage. The majority of GCs are adenocarcinomas (ACs), and the poorly characterized clear cell AC represents a unique subgroup of GCs and is an independent marker of poor prognosis. Even though the prognosis for patients with advanced GC is poor we present a report of a patient with long-term survival despite having liver metastases from clear cell gastric AC.

Case presentation
A 45-year-old male with clear cell gastric AC underwent subtotal gastrectomy and postoperative chemoradiation. Only a year and a half after his initial treatment the disease spread to his liver. He received two lines of chemotherapy treatment within the next two years before a right hepatectomy was suggested. Due to an initially insufficient future liver remnant (FLR), transarterial chemoembolization (TACE) and portal vein embolization (PVE) were performed, which made the surgical procedure possible. Shortly after a disease progression in the remaining liver was detected. In the following three years the patient was treated with a carefully planned combination of systemic therapy and different interventional oncology techniques including selective internal radiation therapy (SIRT) and TACE. And as illustrated, an attentive, patient-tailored, multimodality treatment approach can sometimes greatly benefit our patients as he had an overall survival of 88 months despite the poor prognosis of his disease.

Conclusion
To the best of our knowledge, this report is the first to describe a patient with liver metastases from clear cell gastric AC treated with interventional oncology techniques (PVE, TACE, and SIRT) in combination with other locoregional and systemic therapies thereby presenting that these interventional oncology techniques can be successfully integrated into long-term management of non-conventional liver tumors.
A novel duodenal-release formulation of caraway oil and L-menthol is a safe, effective and well tolerated therapy for functional dyspepsia
Authors: Lacy Brian E. , Chey William D. , Epstein Michael S. , Shah Syed M. , Corsino Patrick , Zeitzoff Linda R. , Cash Brooks D. 
Published: March 2022

Abstract
Background
A randomized, placebo-controlled clinical trial (FDREST) of a novel formulation of caraway oil and L-menthol (COLM-SST) demonstrated symptom relief in patients with functional dyspepsia (FD). Two follow-up studies were conducted to evaluate patient satisfaction, self-regulated dosing, and long-term safety data: FDACT, Functional Dyspepsia Adherence and Compliance Trial, and FDSU36, Functional Dyspepsia Safety Update at 36 months.

Methods
A patient reported outcomes (PRO) questionnaire was designed and distributed online to assess real-world satisfaction and dosing frequency of open-label COLM-SST in patients with FD. A separate study analyzing voluntary safety surveillance data evaluated the frequency and severity of reported adverse events (AEs).

Results
A total of 600 FD patients were enrolled in the PRO study. Ninety five percent of respondents reported a major or moderate improvement in their FD symptoms and 91.7% indicated a major or moderate improvement in quality of life (QOL) using COLM-SST. Between 1 and 4 capsules were consumed daily by 91.2% of respondents, with 56.2% taking them before meals. Symptom relief was rapid, with 86.4% of respondents indicating relief within 2 h of taking COLM-SST. Few adverse events (AEs) were reported (0.0187%) by patients using COLM-SST. No serious AEs were identified.

Conclusion
COLM-SST is safe, well tolerated, and provides rapid relief of FD symptoms. These findings, demonstrated in the FDREST trial, were further supported by a large prospective PRO study evaluating self-regulated dosing frequency, symptom improvement, and QOL. COLM-SST was well-tolerated based on review of AE data at 36 months.
Past dynamics of HIV transmission among men who have sex with men in Montréal, Canada: a mathematical modeling study
Authors: Milwid Rachael M. , Xia Yiqing , Doyle Carla M. , Cox Joseph , Lambert Gilles , Thomas Réjean , Mishra Sharmistha , Grace Daniel , Lachowsky Nathan J. , Hart Trevor A. , Boily Marie-Claude , Maheu-Giroux Mathieu 
Published: March 2022

Abstract
Background
Gay, bisexual, and other men who have sex with men (gbMSM) experience disproportionate risks of HIV acquisition and transmission. In 2017, Montréal became the first Canadian Fast-Track City, setting the 2030 goal of zero new HIV infections. To inform local elimination efforts, we estimate the evolving role of prevention and sexual behaviours on HIV transmission dynamics among gbMSM in Montréal between 1975 and 2019.

Methods
Data from local bio-behavioural surveys were analyzed to develop, parameterize, and calibrate an agent-based model of sexual HIV transmission. Partnership dynamics, HIV’s natural history, and treatment and prevention strategies were considered. The model simulations were analyzed to estimate the fraction of HIV acquisitions and transmissions attributable to specific groups, with a focus on age, sexual partnering level, and gaps in the HIV care-continuum.

Results
The model-estimated HIV incidence peaked in 1985 (2.3 per 100 person years (PY); 90% CrI: 1.4–2.9 per 100 PY) and decreased to 0.1 per 100 PY (90% CrI: 0.04–0.3 per 100 PY) in 2019. Between 2000–2017, the majority of HIV acquisitions and transmissions occurred among men aged 25–44 years, and men aged 35–44 thereafter. The unmet prevention needs of men with > 10 annual anal sex partners contributed 90–93% of transmissions and 67–73% of acquisitions annually. The primary stage of HIV played an increasing role over time, contributing to 11–22% of annual transmissions over 2000–2019. In 2019, approximately 70% of transmission events occurred from men who had discontinued, or never initiated antiretroviral therapy.

Conclusions
The evolving HIV landscape has contributed to the declining HIV incidence among gbMSM in Montréal. The shifting dynamics identified in this study highlight the need for continued population-level surveillance to identify gaps in the HIV care continuum and core groups on which to prioritize elimination efforts.
Importance of early diagnosis and surgical treatment of calcified amorphous tumor-related native valve endocarditis caused by Escherichia coli: a case report
Authors: Koito Shu , Unoki Yuto , Yoshida Keimei , Takemoto Sho , Uchida Takayuki , Matono Takashi 
Published: March 2022

Abstract
Background
Unlike Escherichia coli bacteremia, which is common, E. coli endocarditis is uncommon, particularly in patients with native valve, leading to its delayed diagnosis.

Case presentation
We present a case of infective endocarditis caused by E. coli in a 78-year-old Japanese man with type 2 diabetes, involving persistent bacteremia and vegetation on the mitral valve (measuring 18 × 4.2 mm in diameter). He presented with recurrent fever after antimicrobial treatment for pyelonephritis. He received antibiotic therapy for 6 weeks and required surgical removal of a calcified amorphous tumor and vegetation with mitral valvuloplasty 7 days after admission. Despite an episode of multiple cerebral infarctions, he recovered fully from the infection.

Conclusions
Follow-up blood cultures should be performed for Gram-negative bacilli bacteremia among patients with unknown focus and an atypical clinical course after treatment. Early diagnosis and aggressive surgical intervention are paramount to achieving good clinical outcomes.
Epstein-Barr virus infection associated polymyositis and coronary artery dilation
Authors: Teng Liping , Shen Chencong , Gu Weizhong , Wu Jianqiang , Lu Meiping , Xu Xuefeng 
Published: March 2022

AbstractBackgroundEpstein-Barr virus (EBV) infects more than 90% of the population worldwide. However, chronic active EBV infection (CAEBV) is one of the EBV-positive T- or NK-lymphoproliferative diseases with high morbidity and mortality. Here, we report a case of a 9-year girl with CAEBV, successively presenting with polymyositis and coronary artery dilation (CAD).Case presentationThe girl complained of fatigue for more than 1 month. Muscle strength examinations had no abnormal findings. Blood chemistries showed elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK). Magnetic resonance imaging (MRI) showed spotty high-intensity signals in thigh muscles, and electromyogram suggested myogenic damage. The significant findings were positive EBV antibodies (EBVEA-IgG, EBVCA-IgG, and EBVNA-IgG), increased EBV DNA copies in B, T, and NK cells, and positive EBV-encoded small RNA in biopsy muscle specimen. The girl received ganciclovir, intravenous immunoglobulin, and methylprednisolone, and her symptoms improved. On the 45th day of hospitalization, echocardiograph revealed CAD. She received additional anticoagulants and Tocilizumab. Her condition improved and continued to be followed up at the clinic preparing for hematopoietic stem cell transplantation.ConclusionsThis is the first reported case of CAEBV successively with polymyositis and CAD. This case makes the diagnoses of autoimmune diseases in children more complicated. Careful investigation of hidden CAEBV should be recommended in children with atypical polymyositis or CAD.
Exploring the mechanisms behind HIV drug resistance in sub-Saharan Africa: conceptual mapping of a complex adaptive system based on multi-disciplinary expert insights
Authors: Kiekens Anneleen , Dierckx de Casterlé Bernadette , Pellizzer Giampietro , Mosha Idda H. , Mosha Fausta , Rinke de Wit Tobias F. , Sangeda Raphael Z. , Surian Alessio , Vandaele Nico , Vranken Liesbet , Killewo Japhet , Jordan Michael , Vandamme Anne-Mieke 
Published: March 2022

Abstract
Background
HIV drug resistance (HIVDR) continues to threaten the effectiveness of worldwide antiretroviral therapy (ART). Emergence and transmission of HIVDR are driven by several interconnected factors. Though much has been done to uncover factors influencing HIVDR, overall interconnectedness between these factors remains unclear and African policy makers encounter difficulties setting priorities combating HIVDR. By viewing HIVDR as a complex adaptive system, through the eyes of multi-disciplinary HIVDR experts, we aimed to make a first attempt to linking different influencing factors and gaining a deeper understanding of the complexity of the system.

Methods
We designed a detailed systems map of factors influencing HIVDR based on semi-structured interviews with 15 international HIVDR experts from or with experience in sub-Saharan Africa, from different disciplinary backgrounds and affiliated with different types of institutions. The resulting detailed system map was conceptualized into three main HIVDR feedback loops and further strengthened with literature evidence.

Results
Factors influencing HIVDR in sub-Saharan Africa and their interactions were sorted in five categories: biology, individual, social context, healthcare system and ‘overarching’. We identified three causal loops cross-cutting these layers, which relate to three interconnected subsystems of mechanisms influencing HIVDR. The ‘adherence motivation’ subsystem concerns the interplay of factors influencing people living with HIV to alternate between adherence and non-adherence. The ‘healthcare burden’ subsystem is a reinforcing loop leading to an increase in HIVDR at local population level. The ‘ART overreliance’ subsystem is a balancing feedback loop leading to complacency among program managers when there is overreliance on ART with a perceived low risk to drug resistance. The three subsystems are interconnected at different levels.

Conclusions
Interconnectedness of the three subsystems underlines the need to act on the entire system of factors surrounding HIVDR in sub-Saharan Africa in order to target interventions and to prevent unwanted effects on other parts of the system. The three theories that emerged while studying HIVDR as a complex adaptive system form a starting point for further qualitative and quantitative investigation.
The identification of pregnant women with renal colic who may need surgical intervention
Authors: He Maomao , Lin Xiaoting , Lei Ming , Xu Xiaolan , He Zhihui 
Published: March 2022

Abstract
Background
Renal colic is a surgical emergency in pregnancy that is caused by a range of non-obstetric factors and known to occur more frequently during the second and third trimesters. Several studies have reported that up to 70–80% of stones pass spontaneously during pregnancy. There are some patients will not pass their stones and will ultimately require surgical intervention. Through retrospective analysis of the clinical data of 212 pregnant women with renal colic, the predictive factors of pregnant women with renal colic in need of surgical intervention were determined.

Methods
We conducted a retrospective review of 212 pregnant women presenting with renal colic between 1st January 2009 and 31st December 2020. Univariate and multivariate analyses identified a range of predictive variables for surgical intervention. In addition, we used receiver operating characteristic curve analysis to evaluate the predictive power of our model and created a nomogram for clinical application.

Results
Of the 212 patients presenting with acute renal colic in pregnancy, 100 patients (47.2%) underwent surgical intervention and 112 patients (52.8%) were treated conservatively. Univariate analysis identified significant differences between the two groups with regards to fever, the duration of pain, white blood cells, C-reactive protein, ureteral stone size, hydronephrosis, and stone location. Multivariate analysis further identified a number of independent predictors for surgical intervention, including fever, a duration of pain ≥ 4 days, a ureteral stone size ≥ 8 mm, and moderate or severe hydronephrosis.

Conclusions
We identified several independent predictors for surgical intervention for renal colic in pregnancy. Fever, a duration of pain ≥ 4 days, a ureteral stone size ≥ 8 mm, and moderate/severe hydronephrosis, play significant roles in predicting surgical intervention. Our nomogram can help to calculate the probability of surgical intervention in a simple and efficient manner. Prospective studies are now required to validate our model.
Coexisting CLT in PTC is an independent predictor of tumor aggressiveness for patients aged under 55: a retrospective analysis of 635 patients
Authors: Ma Bing’e , Chen Xiyi , Zhao Zhengping , Yin Xiaoyang , Ji Qin , Zhou Yifan , Ma Chaoqun , Wang Jianhua 
Published: March 2022

AbstractBackgroundThe study was aimed at investigating the potential role of chronic lymphocytic thyroiditis (CLT) in papillary thyroid cancer (PTC) aggressiveness for patients aged below 55, as well as to figure out factors influencing potential recurrence risk in different age groups.MethodsA total of 635 adult patients were retrospectively analyzed. 188 patients were diagnosed with coexistent CLT and the remaining 447 were classified as non-CLT. Then the characteristics of CLT-coexisted patients and non-CLT ones were compared respectively when patients were aged ≥ 55 years or below. The association among postoperative clinicopathological features were also analyzed using multivariate regression. In addition, the prognostic value of several variables relating to high-risk recurrence were estimated within different age groups.ResultsWhen divided in two age groups (55 years as the borderline), non-CLT group (aged below 55 years) had a remarkable frequency of small size lesion (Dmax ≤ 1 cm) compared with CLT-coexisted patients (54.6% to 43.0%,p = 0.02). In addition, non-CLT patients tended to have intrathyroidal extension as opposed to those with coexistent CLT (20.2% to 28.2%,p = 0.05). In multivariate analysis, CLT still significantly acted as an independent risk factor of greater lesion size (Dmin > 1 cm) (OR = 1.7,p = 0.02) and mildly promoted gross extrathyroidal extension (ETE) (OR = 1.4,p = 0.06). However, associations didn’t emerge in the characteristics mentioned above with CLT when patients were ≥ 55 years old. The prognostic value of CLT in high-risk recurrence was evident only in patients aged 35–44 years. (OR = 2.4, 95%CI:1.2–5.4,p = 0.02). Greater lesion size independently promoted gross ETE, no matter patients were aged above 55 years or not. Its prognostic value of high-risk recurrence was significant throughout all age groups.ConclusionThese findings revealed that CLT coexistence might be the unfavorable factor of PTC aggressiveness in patients aged below 55 years. Its role as well as greater tumor size may potentially predict higher recurrence risk according to results figured out in the prediction model.
Alternative medicine: therapeutic effects on gastric original signet ring carcinoma via ascorbate and combination with sodium alpha lipoate
Authors: Chen Weiyu , Xu Lingyun , Chang Edwin , Gowrishankar Gayatri , Ferrara Katherine W. , Gambhir Sanjiv Sam 
Published: March 2022

Abstract
Background
Gastric signet ring cell carcinoma (SRCC) is an aggressive gastric adenocarcinoma with a poor prognosis when diagnosed at an advanced stage. As alternative medicine, two natural supplements (ascorbate (AA) and sodium alpha lipoate (LA)) have been shown to inhibit various cancers with mild side effects.

Methods
These two natural supplements and a series of combinations (AA&LA, AA+LA and LA + AA) were incubated with non-SRCC cells (GPM-1), patient-derived gastric origin SRCC (GPM-2), gastric-origin SRCCs (HSC-39 and KATO-3), human pancreatic (MIA PaCa-2) and ovarian (SKOV-3) cells for evaluating their therapeutic effects. Moreover, these treatments were applied in 3D-cultured organoids to reveal the feasibility of these approaches for in vivo study.

Results
Analyzing their antioxidant capabilities and dose-response curves, we observed that all four gastric cell lines, including three patient-derived cell lines were sensitive to ascorbate (~ 10 mM). The influence of ascorbate incubation time was studied, with a 16-h incubation found to be optimal for in vitro studies. Moreover, a simultaneous combination of AA and LA (AA&LA) did not significantly inhibit cell proliferation, while prior LA treatment increased the growth inhibition of AA therapy (LA + AA). Anti-cancer efficacy of AA was further confirmed in 3D-cultured SRCC (KATO-3) organoids.

Conclusions
This study highlights the potential of AA and LA + AA in treating gastric origin SRCC, and demonstrates the influence of order in which the drugs are administered.
Formulation of teaching strategies for graduation internship based on the experiential learning styles of nursing undergraduates: a non-randomized controlled trial
Authors: Li Cong , Yang Yu , Jing Yancui 
Published: March 2022

AbstractPurposeTo formulate scientific and effective teaching strategies for the graduation internship of nursing undergraduates, in order to improve their holistic clinical competence.MethodA before-after self-controlled study with cluster sampling was performed on the 78 senior nursing undergraduates that underwent a graduation internship at the department. Students were required to fill in the Kolb’s Learning Style Questionnaire and Holistic Clinical Assessment Tool on the date of admission to assess their learning style characteristics and holistic clinical competence, according to which targeted teaching strategies for their graduation internship were formulated. When leaving the department, the students were required to fill in the Holistic Clinical Assessment Tool again to assess the changes in their learning skills after rotation.ResultsIn terms of learning methods, nursing students scored 23.87 ± 6.11, 29.57 ± 5.03, 37.85 ± 6.87, and 28.73 ± 6.70 in Concrete Experience, Reflective Observation, Abstract Conceptualisation, and Active Experimentation, respectively. When the learning styles were ranked by composition ratio, 46 students (58.9%) were assimilators, 18 (23.1%) were convergers, 9 (11.5%) were divergers, and 5 (6.4%) were accommodators. The holistic clinical competence of students after rotation was significantly improved compared to before rotation (P < 0.01).ConclusionClinical teaching strategies for graduation internship that are formulated according to the experiential learning style of nursing undergraduates can effectively improve their learning skills and holistic clinical competence.