bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia
Authors: Dafalla Ommer Mohammed , Alzahrani Mohammed , Sahli Ahmed , Al Helal Mohammed Abdulla , Alhazmi Mohammad Mohammad , Noureldin Elsiddig Mohammed , Mohamed Waheed Sideeg , Hamid Tajeldin Bashir , Abdelhaleem Aymen Awad , Hobani Yahya Ali , Arif Ommar Ali , Bokar Ibrahim Munagi , Hakami Abdulazai Mohammed , Eisa Zaki Manawar 
Published: November 2020

AbstractBackgroundArtemisinin-based combination therapy (ACT) is recommended at the initial phase for treatment ofPlasmodium falciparum, to reduce morbidity and mortality in all countries where malaria is endemic. Polymorphism in portions ofP. falciparumgene encoding kelch (K13)-propeller domains is associated with delayed parasite clearance after ACT. Of about 124 different non-synonymous mutations, 46 have been identified in Southeast Asia (SEA), 62 in sub-Saharan Africa (SSA) and 16 in both the regions. This is the first study designed to analyse the prevalence of polymorphism in theP. falciparum k13-propeller domain in the Jazan region of southwest Saudi Arabia, where malaria is endemic.MethodsOne-hundred and fortyP. falciparumsamples were collected from Jazan region of southwest Saudi Arabia at three different times: 20 samples in 2011, 40 samples in 2016 and 80 samples in 2020 after the implementation of ACT.Plasmodium falciparum kelch13(k13) gene DNA was extracted, amplified, sequenced, and analysed using a basic local alignment search tool (BLAST).ResultsThis study obtained 51 non-synonymous (NS) mutations in three time groups, divided as follows: 6 single nucleotide polymorphisms (SNPs) ‘11.8%’ in samples collected in 2011 only, 3 (5.9%) in 2011and 2016, 5 (9.8%) in 2011 and 2020, 5 (9.8%) in 2016 only, 8 (15.7%) in 2016 and 2020, 14 (27.5%) in 2020 and 10 (19.6%) in all the groups. The BLAST revealed that the 2011 isolates were genetically closer to African isolates (53.3%) than Asian ones (46.7%). Interestingly, this proportion changed completely in 2020, to become closer to Asian isolates (81.6%) than to African ones (18.4%).ConclusionsDespite the diversity of the identified mutations in thek13-propeller gene, these data did not report widespread artemisinin-resistant polymorphisms in the Jazan region where these samples were collected. Such a process would be expected to increase frequencies of mutations associated with the resistance of ACT.
Circular RNA hsa_circ_0004872 inhibits gastric cancer progression via the miR-224/Smad4/ADAR1 successive regulatory circuit
Authors: Ma Cunying , Wang Xiaoying , Yang Fenghua , Zang Yichen , Liu Jiansong , Wang Xinyi , Xu Xia , Li Wenjuan , Jia Jihui , Liu Zhifang 
Published: November 2020

Abstract

Background
Emerging evidence has shown that circular RNAs (circRNAs) play a crucial regulatory role in the occurrence and development of cancer. Exploring the roles and mechanisms of circRNAs in tumorigenesis and progression may help to identify new diagnostic markers and therapeutic targets. In the present study, we investigated the role and regulatory mechanism of hsa_circ_0004872 in gastric cancer (GC).

Methods
qRT-PCR was used to determine the expression of hsa_circ_0004872 in GC tissues and cells. EdU, CCK-8, transwell and scratch wound healing assays were used to assess the role of hsa_circ_0004872 in GC cell proliferation, invasion and migration, respectively. Subcutaneous and tail vein tumor injections in nude mice were used to assess the role of hsa_circ_0004872 in vivo. RIP assay, biotin-coupled probe pull-down assay, FISH and luciferase reporter assay were performed to confirm the relationship between hsa_circ_0004872 and the identified miRNA. ChIP assay, luciferase reporter assay and western blot were used to determine the direct binding of Smad4 to the promoter of the ADAR1 gene.

Results
In this study, we found that hsa_circ_0004872 was dramatically downregulated in GC tissues compared with adjacent noncancerous tissues. The expression level of hsa_circ_0004872 was associated with tumor size and local lymph node metastasis. Enforced expression of hsa_circ_0004872 inhibited the proliferation, invasion and migration of GC cells, whereas knockdown of hsa_circ_0004872 had the opposite effects. Nude mice experiments showed that ectopic expression of hsa_circ_0004872 dramatically inhibited tumor growth and metastasis in vivo. Moreover, we demonstrated that hsa_circ_0004872 acted as a “molecular sponge” for miR-224 to upregulate the expression of the miR-224 downstream targets p21 and Smad4. Importantly, we found that the RNA-editing enzyme ADAR1 inhibited hsa_circ_0004872 expression and further led to the upregulation of miR-224. Smad4, the downstream target of miR-224, could further affect hsa_circ_0004872 levels by directly binding to the promoter region of ADAR1 to inhibit ADAR1 expression.

Conclusions
Our findings showed that hsa_circ_0004872 acted as a tumor suppressor in GC by forming a negative regulatory loop consisting of hsa_circ_0004872/miR-224/Smad4/ADAR1. Thus, hsa_circ_0004872 may serve as a potential biomarker and therapeutic target for GC.
Elucidating the cellular response of silver nanoparticles as a potential combinatorial agent for cisplatin chemotherapy
Authors: Rank Miranda Renata , Pereira da Fonseca Micaella , Korzeniowska Barbara , Skytte Lilian , Lund Rasmussen Kaare , Kjeldsen Frank 
Published: November 2020

Abstract

Background
Combination chemotherapy uses drugs that target different cancer hallmarks, resulting in synergistic or additive toxicity. This strategy enhances therapeutic efficacy as well as minimizes drug resistance and side effects. In this study, we investigated whether silver nanoparticles act as a combinatorial partner to cisplatin. In so doing, we compared post-exposure biological endpoints, intracellular drug accumulation, and changes in the proteome profile of tumoral and normal cell lines.

Results
Combinatorial exposure corresponded to cytotoxicity and oxidative stress in both cell lines, yet was substantially more effective against tumoral cells. Proteome analysis revealed that proteins related to energy metabolism pathways were upregulated in both cell lines, suggesting that combinatorial exposure corresponded to energetic modulation. However, proteins and upstream regulators involved in the cell cycle were downregulated, indicating reduced cell proliferation. The response to oxidative stress was markedly different in both cell lines; downregulation of antioxidant proteins in tumoral cells, yet upregulation of the antioxidant defense system in normal cells. These outcomes may have avoided higher cell death rates in normal cells.

Conclusions
Taken together, our results indicate that combining silver nanoparticles with cisplatin increases the biological activity of the latter, and the combination warrants further exploration for future therapies.
Enhanced antitumor effects of follicle-stimulating hormone receptor-mediated hexokinase-2 depletion on ovarian cancer mediated by a shift in glucose metabolism
Authors: Zhang Meng , Liu Qiyu , Zhang Mingxing , Cao Cong , Liu Xiaoxia , Zhang Mengyu , Li Guiling , Xu Congjian , Zhang Xiaoyan 
Published: November 2020

Abstract

Background
Most cancers favor glycolytic-based glucose metabolism. Hexokinase-2 (HK2), the first glycolytic rate-limiting enzyme, shows limited expression in normal adult tissues but is overexpressed in many tumor tissues, including ovarian cancer. HK2 has been shown to be correlated with the progression and chemoresistance of ovarian cancer and could be a therapeutic target. However, the systemic toxicity of HK2 inhibitors has limited their clinical use. Since follicle-stimulating hormone (FSH) receptor (FSHR) is overexpressed in ovarian cancer but not in nonovarian healthy tissues, we designed FSHR-mediated nanocarriers for HK2 shRNA delivery to increase tumor specificity and decrease toxicity.

Results
HK2 shRNA was encapsulated in a polyethylene glycol-polyethylenimine copolymer modified with the FSH β 33–53 or retro-inverso FSH β 33–53 peptide. The nanoparticle complex with FSH peptides modification effectively depleted HK2 expression and facilitated a shift towards oxidative glucose metabolism, with evidence of increased oxygen consumption rates, decreased extracellular acidification rates, and decreased extracellular lactate and glucose consumption in A2780 ovarian cancer cells and cisplatin-resistant A2780CP counterpart cells. Consequently, cell proliferation, invasion and migration were significantly inhibited, and tumor growth was suppressed even in cisplatin-resistant ovarian cancer. No obvious systemic toxicity was observed in mice. Moreover, the nanoparticle complex modified with retro-inverso FSH peptides exhibited the strongest antitumor effects and effectively improved cisplatin sensitivity by regulating cisplatin transport proteins and increasing apoptosis through the mitochondrial pathway.

Conclusions
These results established HK2 as an effective therapeutic target even for cisplatin-resistant ovarian cancer and suggested a promising targeted therapeutic approach.
Content validation of the Kamath and Stothard questionnaire for carpal tunnel syndrome diagnosis: a cognitive interviewing study
Authors: Dabbagh Armaghan , MacDermid Joy C. , Packham Tara L. , Macedo Luciana G. 
Published: November 2020

Abstract

Background
Accurate diagnosis of carpal tunnel syndrome (CTS) is essential for directing appropriate treatment; and for making decisions about work injury claims. The Kamath and Stothard Questionnaire (KSQ) is a self-reported tool used for the diagnosis of CTS. Comprehensibility and comprehensiveness of this questionnaire are critical to diagnostic performance and need to be established. The purpose of the study was to describe how potential respondents, clinicians, and measurement researchers interpret KSQ questions in order to identify and resolve potential sources of misclassification.

Methods
Hand therapists, measurement researchers, participants with CTS, and a control group were interviewed using cognitive interviewing techniques (talk aloud, semi-structured interview probes) in Hamilton, Canada. All interviews were recorded and transcribed verbatim. A directed content analysis was done to analyze the interviews using a previously established framework.

Findings
Eighteen participants were interviewed. Areas, where questions were unclear to some participants, were recorded and categorized into five themes: Clarity and Comprehension (52%), Relativeness (38%), Inadequate Response Definition (4%), Perspective Modifiers (4%), and Reference Point (2%). Respondents also identified several symptoms of CTS that are not covered by the KSQ that might be of diagnostic value, e.g., weakness and dropping items.

Conclusion
The content validity of the current iteration of the KSQ was not established. The problematic questions identified in the study have been reported to have low specificity and negative predictive values in a previous quantitative study. The content validity issues identified may explain the poor performance. Recommendations were made to modify the wording of the KSQ and the potential addition of three new questions. Future studies should determine whether the modified questionnaire can provide better diagnostic accuracy and psychometric properties. The results of this study may assist in ruling in or out CTS diagnosis to a wide variety of target audience, such as hand specialists, physical and occupational therapists, as well as family doctors.
Experiencing earthquake in the first trimester of the fetal life increases subsequent diabetes risk in the adulthood: a cross-sectional study
Authors: Li Na , Song Mei , Wang Lan , Zhao Xiao-chuan , Wang Ran , Gao Yuan-yuan , Yu Lu-lu , An Cui-xia , Wang Xue-yi 
Published: November 2020

Abstract

Objective
To investigate the long-term effect of prenatal exposure to earthquake stress on diabetes risk in the adulthood.

Methods
This study included employees of Tangshan Kailuan Mining Group between July 29, 1976 and April 28, 1977. The exposure group included subjects who experienced the Tangshan Earthquake during their prenatal period and who had lived in Tangshan since birth. The non-exposure group included subjects who were born 1–1.9 years after the earthquake and who had lived in Tangshan since birth. A questionnaire was designed that included sociodemographic information, conditions during pregnancy, and earthquake experience. Anthropometric measurements including height and weight, body mass index (BMI), waist circumference were made. Fasting plasma glucose (FPG) and lipid profiles were also determined.

Results
Totally 947 subjects were included with 397 subjects in the exposed group and 550 subjects in the non-exposed group. The diabetes rate is significant different in these four groups(χ2 =8.045, P = 0.045). Moreover, 11.8, 7.5 and 8.0% of the subjects who were exposed to earthquake in the 1st, 2nd, and 3rd trimester of pregnancy had diabetes. 5.1% of the subjects had diabetes in non-exposure group. Our multivariate analysis showed that 1st trimester (OR 2.481, 95%CI 1.02, 6.034; P = 0.045) and loss of family members during earthquake (OR 2.452, 95%CI 1.293, 4.653; P = 0.006) were associated with significantly increased risk of diabetes.

Conclusions
Exposure to earthquake during the first trimester of pregnancy and experience of family member loss in the earthquake significantly increased the subsequent risk of diabetes in the middle age (36–39 years of age). Our data suggest that earthquake experience in the early pregnancy has a longer-term effect on diabetes risk during adulthood.
Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice
Authors: Xu Yanqun , Liang Yideng , Parunov Leonid , Despres Daryl , Eckhaus Michael , Scott Dorothy , Ovanesov Mikhail , Struble Evi B. 
Published: November 2020

AbstractBackgroundPregnant women are at increased risk of thrombotic adverse events. Plasma derived immune globulin (IG) products, which are used in pregnancy for various indications, may contain procoagulant impurity activated coagulation factor XI (FXIa). Procoagulant IG products have been associated with increased thrombogenicity but their effect in pregnancy is unknown.MethodsLate pregnant (gestation days 17–20) or early lactation (days 1–3) and control female mice were treated with IGs supplemented with human FXIa then subjected to ferric chloride (FeCl3) vessel injury. Occlusion of blood vessel was assessed by recording blood velocity in the femoral vein for 20 min using doppler ultrasound laser imaging. FXIa dose was selected by the ability to increase thrombin generation in mouse plasma in vitro.ResultsFXIa produced robust thrombin generation in mouse plasma ex vivo. Following FeCl3injury, pregnant and non-pregnant mice receiving IG + FXIa exhibited faster reduction of blood velocity in femoral vein compared to IG alone or untreated controls. In vitro, thrombin generation in plasma samples collected after thrombosis in FXIa-treated animals was elevated and could be reduced by anti-FXI antibody.ConclusionsOur results suggest that intravenously-administered FXIa may contribute to thrombosis at the site of vascular injury in both pregnant and non-pregnant animals.
Molecular characterization of breast cancer: a potential novel immune-related lncRNAs signature
Authors: Lai Jianguo , Chen Bo , Zhang Guochun , Li Xuerui , Mok Hsiaopei , Liao Ning 
Published: November 2020

AbstractBackgroundAccumulating evidence has demonstrated that immune-related lncRNAs (IRLs) are commonly aberrantly expressed in breast cancer (BC). Thus, we aimed to establish an IRL-based tool to improve prognosis prediction in BC patients.MethodsWe obtained IRL expression profiles in large BC cohorts (N = 911) from The Cancer Genome Atlas (TCGA) database. Then, in light of the correlation between each IRL and recurrence-free survival (RFS), we screened prognostic IRL signatures to construct a novel RFS nomogram via a Cox regression model. Subsequently, the performance of the IRL-based model was evaluated through discrimination, calibration ability, risk stratification ability and decision curve analysis (DCA).ResultsA total of 52 IRLs were obtained from TCGA. Based on multivariate Cox regression analyses, four IRLs (A1BG-AS1, AC004477.3, AC004585.1 and AC004854.2) and two risk parameters (tumor subtype and TNM stage) were utilized as independent indicators to develop a novel prognostic model. In terms of predictive accuracy, the IRL-based model was distinctly superior to the TNM staging system (AUC: 0.728 VS 0.673,P = 0.010). DCA indicated that our nomogram had favorable clinical practicability. In addition, risk stratification analysis showed that the IRL-based tool efficiently divided BC patients into high- and low-risk groups (P < 0.001).ConclusionsA novel IRL-based model was constructed to predict the risk of 5-year RFS in BC. Our model can improve the predictive power of the TNM staging system and identify high-risk patients with tumor recurrence to implement more appropriate treatment strategies.
Low-volume high-intensity interval training improves cardiometabolic health, work ability and well-being in severely obese individuals: a randomized-controlled trial sub-study
Authors: Reljic Dejan , Frenk Fabienne , Herrmann Hans J. , Neurath Markus F. , Zopf Yurdagül 
Published: November 2020

Abstract
Background
Obesity is associated with impaired health and lower work ability. Increased physical activity is a cornerstone in the treatment of obesity and related risk factors. Recently, high-intensity interval training (HIIT) has emerged as a popular exercise option. However, data regarding the effects on cardiometabolic health, perceived work ability and well-being in severely obese individuals are lacking.

Methods
Sixty-five obese individuals with sedentary occupation (48.7 ± 9.9 years, BMI: 39.6 ± 7.1 kg/m2) were randomly allocated to an extremely time-efficient HIIT (5 × 1 min at 80–95% maximal heart rate on cycle ergometers, 2×/week for 12 weeks) or an inactive control group (CON). Both groups received nutritional counseling to support weight loss. Primary outcome was maximal oxygen uptake (VO2max), secondary outcomes were cardiometabolic risk indices, body composition, work ability index (WAI), quality of life (QoL, EQ-5D-5L-questionnaire) and perceived stress (PSQ-questionnaire).

Results
Mean body weight reduction was 5.3 kg [95% confidence interval (95% CI) − 7.3 to − 3.3 kg] in the HIIT group (P < 0.001) and 3.7 kg (95% CI − 5.3 to − 2.1 kg) in CON (P < 0.001), respectively. Only the HIIT group showed significant (P < 0.001) changes in VO2max [+ 3.5 mL/kg/min (95% CI 2.5 to 4.6 mL/kg/min)], waist circumference [–7.5 cm (95% CI − 9.8 to − 5.1 kg)], mean arterial blood pressure [− 11 mmHg (95% CI − 14 to − 8 mmHg)], WAI [+ 3.0 points (95% CI 1.7 to 4.3 points)] and QoL [+ 10% (95% CI 5 to 16%)]. In CON, none of these parameters improved significantly.

Conclusions
Low-volume HIIT may induce significant improvements in cardiometabolic health, especially VO2max, WAI and well-being in obese individuals after only 12 weeks. Our results underpin the wide range of benefits on health and subjective measures through exercise that go well beyond simple weight loss through dietary restriction alone.
Trial registration: ClinicalTrials.gov Id: NCT03306069. Registered 10 October 2017, https://clinicaltrials.gov/ct2/show/NCT03306069.
A brief guide to the science and art of writing manuscripts in biomedicine
Authors: Forero Diego A. , Lopez-Leon Sandra , Perry George 
Published: November 2020

Abstract
Publishing articles in international scientific journals is the primary method for the communication of validated research findings and ideas. Journal articles are commonly used as a major input for evaluations of researchers and institutions. Few articles have been published previously about the different aspects needed for writing high-quality articles. In this manuscript, we provide an updated and brief guide for the multiple dimensions needed for writing manuscripts in the health and biological sciences, from current, international and interdisciplinary perspectives and from our expertise as authors, peer reviewers and editors. We provide key suggestions for writing major sections of the manuscript (e.g. title, abstract, introduction, methods, results and discussion), for submitting the manuscript and bring an overview of the peer review process and of the post-publication impact of the articles.
Transcriptome analysis identifies putative multi-gene signature distinguishing benign and malignant pancreatic head mass
Authors: Chhatriya Bishnupriya , Mukherjee Moumita , Ray Sukanta , Saha Barsha , Lahiri Somdatta , Halder Sandip , Ghosh Indranil , Khamrui Sujan , Das Kshaunish , Bhattacharjee Samsiddhi , Mohapatra Saroj Kant , Goswami Srikanta 
Published: November 2020

AbstractBackgroundMost often, the patients with pancreatic diseases are presented with a mass in pancreatic head region and existing methods of diagnosis fail to confirm whether the head mass is malignant or benign. As subsequent management of the disease hugely depends on the correct diagnosis, we wanted to explore possible biomarkers which could distinguish benign and malignant pancreatic head masses.MethodsIn order to address that gap, we performed a case–control study to identify genome-wide differentially expressed coding and noncoding genes between pancreatic tissues collected from benign and malignant head masses. These genes were next shortlisted using stringent criteria followed by selection of top malignancy specific genes. They subsequently got validated by quantitative RT-PCR and also in other patient cohorts. Survival analysis and ROC analysis were also performed.ResultsWe identified 55 coding and 13 noncoding genes specific for malignant pancreatic head masses. Further shortlisting and validation, however, resulted in 5 coding genes as part of malignancy specific multi-gene signature, which was validated in three independent patient cohorts of 145 normal and 153 PDAC patients. We also found that overexpression of these genes resulted in survival disadvantage in the patients and ROC analysis identified that combination of 5 coding genes had the AUROC of 0.94, making them potential biomarker.ConclusionsOur study identified a multi-gene signature comprising of 5 coding genes (CDCA7,DLGAP5,FOXM1,TPX2andOSBPL3) to distinguish malignant head masses from benign ones.