bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of insulin resistance on subclinical left ventricular dysfunction in normal weight and overweight/obese japanese subjects in a general community
Authors: Hirose Kazutoshi , Nakanishi Koki , Daimon Masao , Sawada Naoko , Yoshida Yuriko , Iwama Kentaro , Yamamoto Yuko , Ishiwata Jumpei , Hirokawa Megumi , Koyama Katsuhiro , Nakao Tomoko , Morita Hiroyuki , Di Tullio Marco R. , Homma Shunichi , Komuro Issei 
Published: January 2021

Abstract
Background
Insulin resistance carries increased risk of heart failure, although the pathophysiological mechanisms remain unclear. LV global longitudinal strain (LVGLS) assessed by speckle-tracking echocardiography has emerged as an important tool to detect early LV systolic abnormalities. This study aimed to investigate the association between insulin resistance and subclinical left ventricular (LV) dysfunction in a sample of the general population without overt cardiac disease.

Methods
We investigated 539 participants who voluntarily underwent extensive cardiovascular health check including laboratory test and speckle-tracking echocardiography. Glycemic profiles were categorized into 3 groups according to homeostatic model assessment of insulin resistance (HOMA-IR): absence of insulin resistance (HOMA-IR < 1.5), presence of insulin resistance (HOMA-IR ≥ 1.5) and diabetes mellitus (DM). Multivariable logistic regression models were conducted to evaluate the association between abnormal glucose metabolism and impaired LVGLS (> − 16.65%).

Results
Forty-five (8.3%) participants had DM and 66 (12.2%) had abnormal HOMA-IR. LV mass index and E/e′ ratio did not differ between participants with and without abnormal HOMA-IR, whereas abnormal HOMA-IR group had significantly decreased LVGLS (− 17.6 ± 2.6% vs. − 19.7 ± 3.1%, p < 0.05). The prevalence of impaired LVGLS was higher in abnormal HOMA-IR group compared with normal HOMA-IR group (42.4% vs. 14.0%) and similar to that of DM (48.9%). In multivariable analyses, glycemic abnormalities were significantly associated with impaired LVGLS, independent of traditional cardiovascular risk factors and pertinent laboratory and echocardiographic parameters [adjusted odds ratio (OR) 2.38, p = 0.007 for abnormal HOMA-IR; adjusted OR 3.02, p = 0.003 for DM]. The independent association persisted even after adjustment for waist circumference as a marker of abdominal adiposity. Sub-group analyses stratified by body mass index showed significant association between abnormal HOMA-IR and impaired LVGLS in normal weight individuals (adjusted OR 4.59, p = 0.001), but not in overweight/obese individuals (adjusted OR 1.62, p = 0.300).

Conclusions
In the general population without overt cardiac disease, insulin resistance carries independent risk for subclinical LV dysfunction, especially in normal weight individuals.
Factors associated with access and adherence to artemisinin‐based combination therapy (ACT) for children under five: a secondary analysis of a national survey in Sierra Leone
Authors: Banek Kristin , Webb Emily L. , Doogue Emily Bostick , Smith Samuel Juana , Chandramohan Daniel , Staedke Sarah G. 
Published: January 2021

Abstract
Background
Access and adherence to artemisinin-based combination therapy (ACT) are key challenges to effective malaria treatment. A secondary analysis of the Sierra Leone malaria Knowledge, Attitudes, and Practices (mKAP) survey was conducted to investigate access and adherence to ACT for the treatment of fever in children under-five.

Methods
The mKAP was a nationally representative, two-stage cluster-sample survey, conducted in 2012. Thirty primary sampling units per district were randomly selected using probability proportionate to size, based on national census estimates; 14 households were subsequently randomly selected and enrolled per sampling unit. The analysis was restricted to children under-five with fever in the past two weeks. Factors associated with access and adherence were assessed using multivariate logistic regression.

Results
Of 5169 enrolled households, 1456 reported at least one child under-five with fever in the past two weeks. Of the 1641 children from these households, 982 (59.8%) received any treatment for fever and were analysed for access to ACT; 469 (47.6%) received ACT and 466 were analysed for treatment adherence. Only 222 (47.4%) febrile children received ACT and completed 3-day treatment. In an adjusted analysis, factors associated with ACT access included knowledge of ACT (odds ratio [OR] 2.78, 95% CI 2.02–3.80; p < 0.001), knowledge of insecticide-treated nets (ITNs) (OR 1.84, 95% CI 1.29–2.63; p = 0.001), source of care (public health facility vs. other; OR 1.86, 95% CI 1.27–2.72, p = 0.001), geographic region (East vs. West; OR 2.30, 95% CI 1.20–4.44; p = 0.025), and age (24–59 vs. 0–23 months; OR 1.45, 95% CI 1.07–1.96; p = 0.016). The only factor associated with ACT adherence was time to treatment; children treated within 24 h were less likely to adhere (OR 0.55, 95% CI 0.34–0.89; p = 0.015).

Conclusions
In 2012, access and adherence to ACT remained low in Sierra Leone. Knowledge of ACT and ITNs, and seeking care in the public sector, were most strongly associated with ACT access. National surveys provide important information on anti-malarial access and could be expanded to measure treatment adherence.
Laparoscopic-assisted disinvagination and polypectomy for multiple intussusceptions induced by small intestinal polyps in patients with Peutz-Jeghers syndrome: a case report
Authors: Yamamoto Masaaki , Iwamoto Kazuya , Suzuki Rei , Mukai Yosuke , Takeoka Tomohira , Asukai Kei , Shinno Naoki , Hara Hisashi , Kanemura Takashi , Nakai Nozomu , Hasegawa Shinichiro , Sugimura Keijiro , Haraguchi Naotsugu , Nishimura Junichi , Wada Hiroshi , Takahashi Hidenori , Matsuda Chu , Yasui Masayoshi , Omori Takeshi , Miyata Hiroshi , Ohue Masayuki , Murata Masaru 
Published: January 2021

Abstract
Background
Peutz–Jeghers syndrome (PJS) is a very rare autosomal dominant genetic disorder characterized by hamartomatous polyps in the gastrointestinal tract and hyperpigmentation of the lips, hands, and feet. The hamartomatous polyps in the small intestine often cause intussusception and bleeding.

Case presentation
A 62-year-old male was hospitalized for treatment of deep vein thrombosis and pulmonary embolism. In the small intestine, computed tomography showed three small polyps with intussusceptions. Since the patient had gastrointestinal polyposis and pigmentation of his lips, fingers, and toes, he was diagnosed with PJS. After an inferior vena cava filter was placed, he underwent laparoscopic-assisted surgery. The polyps causing intussusception were resected as far as possible without intestinal resection, since they had caused progressive anemia and might cause intestinal obstruction in the future. The patient was discharged from the hospital on postoperative day 9 without complications.

Conclusions
Laparoscopic-assisted disinvagination and polypectomy is a useful, minimally invasive treatment for multiple intussusceptions caused by small intestinal polyps in patients with PJS.
Patient-derived organoid (PDO) platforms to facilitate clinical decision making
Authors: Liu Lisa , Yu Lei , Li Zhichao , Li Wujiao , Huang WeiRen 
Published: January 2021

AbstractBased on recent advances in organoid research as well as the need to find more accurate models for drug screening in cancer research, patient-derived organoids have emerged as an effective in vitro model system to study cancer. Showing numerous advantages over 2D cell lines, 3D cell lines, and primary cell culture, organoids have been applied in drug screening to demonstrate the correlation between genetic mutations and sensitivity to targeted therapy. Organoids have also been used in co-clinical trials to compare drug responses in organoids to clinical responses in the corresponding patients. Numerous studies have reported the successful use of organoids to predict therapy response in cancer patients. Recently, organoids have been adopted to predict treatment response to radiotherapy and immunotherapy. The development of high throughput drug screening and organoids-on-a-chip technology can advance the use of patient-derived organoids in clinical practice and facilitate therapeutic decision-making.
Predicting the number of article citations in the field of attention-deficit/hyperactivity disorder (ADHD) with the 100 top-cited articles since 2014: a bibliometric analysis
Authors: Lin Chien-Ho , Chien Tsair-Wei , Yan Yu-Hua 
Published: January 2021

Abstract
Background
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children or early adolescents with an estimated worldwide prevalence of 7.2%. Numerous articles related to ADHD have been published in the literature. However, which articles had ultimate influence is still unknown, and what factors affect the number of article citations remains unclear as well. This bibliometric analysis (1) visualizes the prominent entities with 1 picture using the top 100 most-cited articles, and (2) investigates whether medical subject headings (i.e., MeSH terms) can be used in predicting article citations.

Methods
By searching the PubMed Central® (PMC) database, the top 100 most-cited abstracts relevant to ADHD since 2014 were downloaded. Citation rank analysis was performed to compare the dominant roles of article types and topic categories using the pyramid plot. Social network analysis (SNA) was performed to highlight prominent entities for providing a quick look at the study result. The authors examined the MeSH prediction effect on article citations using its correlation coefficients (CC).

Results
The most frequent article types and topic categories were research support by institutes (56%) and epidemiology (28%). The most productive countries were the United States (42%), followed by the United Kingdom (13%), Germany (9%), and the Netherlands (9%). Most articles were published in the Journal of the American Academy of Child and Adolescent Psychiatry (15%) and JAMA Psychiatry (9%). MeSH terms were evident in prediction power on the number of article citations (correlation coefficient = 0.39; t = 4.1; n = 94; 6 articles were excluded because they do not have MeSH terms).

Conclusions
The breakthrough was made by developing 1 dashboard to display 100 top-cited articles on ADHD. MeSH terms can be used in predicting article citations on ADHD. These visualizations of the top 100 most-cited articles could be applied to future academic pursuits and other academic disciplines.
HSP22 (HSPB8) positively regulates PGF2α-induced synthesis of interleukin-6 and vascular endothelial growth factor in osteoblasts
Authors: Kuroyanagi Gen , Sakai Go , Otsuka Takanobu , Yamamoto Naohiro , Fujita Kazuhiko , Kawabata Tetsu , Matsushima-Nishiwaki Rie , Kozawa Osamu , Tokuda Haruhiko 
Published: January 2021

Abstract
Background
Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitous expression in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF and the mechanism of MC3T3-E1 cells.

Methods
MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting.

Results
The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 downregulation.

Conclusions
Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.
Unilateral percutaneous vertebroplasty for osteoporotic lumbar compression fractures: a comparative study between transverse process root-pedicle approach and conventional transpedicular approach
Authors: Zhang Wenwu , Liu Shenpeng , Liu Xianhua , Li Xiang , Wang Le , Wan Yong 
Published: January 2021

Abstract
Purpose
Percutaneous vertebroplasty (PVP) is a routine operation for the treatment of osteoporotic lumbar compression fractures (OLCFs). As is well known, unilateral puncture is a common method. However, with the conventional transpedicular approach (CTPA), the cement may be asymmetrically dispersed, so some surgeons use the transverse process root-pedicle approach (TPRPA). The objective of this study was to compare the clinical results and bone cement distribution of PVP for OLCF with unilateral TPRPA and CTPA to identify the advantages and disadvantages of the two surgical options.

Patients and methods
From January 2016 to June 2019, seventy-two elderly patients who underwent unilateral PVP for single-level OLCF were retrospectively reviewed. Operation time, injection amount and type of bone cement distribution, and bone cement leakage and surgical complications were recorded. The visual analog scale (VAS) scores and Oswestry disability index (ODI) scores were used to evaluate the clinical results. All patients were followed up for more than 12 months, and the assessment was based primarily on clinical and radiological outcomes.

Results
There were significant differences in the surgical time and the volume and the type of bone cement distribution and the lost of operative vertebra height between the two groups. However, there was no significant difference in bone cement leakage. Moreover, there were no significant differences in VAS and ODI between the two groups at 2 days and 12 months after the operation.

Conclusions
Unilateral TPRPA and CTPA are practical and feasible methods in PVP for the treatment of OLCF, and they have similar clinical effects. However, TPRPA has the advantages of a better distribution of bone cement and a shorter operation time and a better maintenance effect of injured vertebra height, without increasing the rate of bone cement leakage.
Impact of long-term elosulfase alfa treatment on clinical and patient-reported outcomes in patients with mucopolysaccharidosis type IVA: results from a Managed Access Agreement in England
Authors: Cleary Maureen , Davison James , Gould Rachel , Geberhiwot Tarekegn , Hughes Derralynn , Mercer Jean , Morrison Alexandra , Murphy Elaine , Santra Saikat , Jarrett James , Mukherjee Swati , Stepien Karolina M. 
Published: January 2021

Abstract
Background
We present baseline characteristics and follow-up data of a Managed Access Agreement (MAA), including patients with mucopolysaccharidosis IVA (MPS IVA) receiving elosulfase alfa enzyme replacement therapy (ERT) in England on a conditional basis. Patients enrolled in the MAA programme are reviewed on an annual basis. Therapy can be continued if patients are compliant, able to tolerate infusions, and meet four out of five pre-defined clinical and patient-reported outcomes (PRO) criteria. Baseline and follow-up clinical and PRO data are presented for all participants who completed ≥ 1 year of assessments in the MAA.

Results
The analysis included data from 55 patients, including 26 patients previously enrolled in clinical trials and 29 who started ERT after enrolling in the MAA. In patients with both baseline and follow-up data, mean 6-min walk test distance increased from 217 m at baseline to 244 m after a mean follow-up of 4.9 years. Improvement or stabilisation was seen regardless of age at treatment initiation or duration of treatment. Mean forced vital capacity and forced expiratory volume in 1 s were 0.87 L and 0.78 L, respectively at baseline and 1.05 L and 0.88 L after a mean follow-up of 5.5 years. PRO data showed overall improvements over time in Mobility, Self-care, and Caregiver assistance scores of the MPS-Health Assessment Questionnaire, relatively stable quality of life, and some improvements in pain scores.

Conclusions
The MAA data confirm the effects of elosulfase alfa on clinical and PRO results observed in the clinical trials and provide real-world evidence for long-term stabilisation in these measures, suggesting a positive impact on the natural history of MPS IVA.
PDGFRβ is an essential therapeutic target for BRCA1-deficient mammary tumors
Authors: Bai Feng , Liu Shiqin , Liu Xiong , Hollern Daniel P. , Scott Alexandria , Wang Chuying , Zhang Lihan , Fan Cheng , Fu Li , Perou Charles M. , Zhu Wei-Guo , Pei Xin-Hai 
Published: January 2021

Abstract
Background
Basal-like breast cancers (BLBCs) are a leading cause of cancer death due to their capacity to metastasize and lack of effective therapies. More than half of BLBCs have a dysfunctional BRCA1. Although most BRCA1-deficient cancers respond to DNA-damaging agents, resistance and tumor recurrence remain a challenge to survival outcomes for BLBC patients. Additional therapies targeting the pathways aberrantly activated by BRCA1 deficiency are urgently needed.

Methods
Most BRCA1-deficient BLBCs carry a dysfunctional INK4-RB pathway. Thus, we created genetically engineered mice with Brca1 loss and deletion of p16INK4A, or separately p18INK4C, to model the deficient INK4-RB signaling in human BLBC. By using these mutant mice and human BRCA1-deficient and proficient breast cancer tissues and cells, we tested if there exists a druggable target in BRCA1-deficient breast cancers.

Results
Heterozygous germline or epithelium-specific deletion of Brca1 in p18INK4C- or p16INK4A-deficient mice activated Pdgfrβ signaling, induced epithelial-to-mesenchymal transition, and led to BLBCs. Confirming this role, targeted deletion of Pdgfrβ in Brca1-deficient tumor cells promoted cell death, induced mesenchymal-to-epithelial transition, and suppressed tumorigenesis. Importantly, we also found that pharmaceutical inhibition of Pdgfrβ and its downstream target Pkcα suppressed Brca1-deficient tumor initiation and progression and effectively killed BRCA1-deficient cancer cells.

Conclusions
Our work offers the first genetic and biochemical evidence that PDGFRβ-PKCα signaling is repressed by BRCA1, which establishes PDGFRβ-PKCα signaling as a therapeutic target for BRCA1-deficient breast cancers.
Optimized RNA-targeting CRISPR/Cas13d technology outperforms shRNA in identifying functional circRNAs
Authors: Zhang Yang , Nguyen Tuan M. , Zhang Xiao-Ou , Wang Limei , Phan Tin , Clohessy John G. , Pandolfi Pier Paolo 
Published: January 2021

AbstractShort hairpin RNAs (shRNAs) are used to deplete circRNAs by targeting back-splicing junction (BSJ) sites. However, frequent discrepancies exist between shRNA-mediated circRNA knockdown and the corresponding biological effect, querying their robustness. By leveraging CRISPR/Cas13d tool and optimizing the strategy for designing single-guide RNAs against circRNA BSJ sites, we markedly enhance specificity of circRNA silencing. This specificity is validated in parallel screenings by shRNA and CRISPR/Cas13d libraries. Using a CRISPR/Cas13d screening library targeting > 2500 human hepatocellular carcinoma-related circRNAs, we subsequently identify a subset of sorafenib-resistant circRNAs. Thus, CRISPR/Cas13d represents an effective approach for high-throughput study of functional circRNAs.
Synthesis and biological evaluation of heterocyclic 1,2,4-triazole scaffolds as promising pharmacological agents
Authors: Kumari Mukesh , Tahlan Sumit , Narasimhan Balasubramanian , Ramasamy Kalavathy , Lim Siong Meng , Shah Syed Adnan Ali , Mani Vasudevan , Kakkar Saloni 
Published: January 2021

Abstract
Background
Triazole is an important heterocyclic moiety that occupies a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms i.e. 1,2,4-triazole and 1,2,3-triazole and is used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, anti-urease, anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic and antimigraine agents.

Methods
The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards.

Results, discussion and conclusion
The biological screening results reveal that the compounds T5 (MICBS, EC = 24.7 µM, MICPA, CA = 12.3 µM) and T17 (MICAN = 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MICCipro = 18.1 µM, MICAmo = 17.1 µM) and fluconazole (MICFlu = 20.4 µM), respectively. The antioxidant evaluation showed that compounds T2 (IC50 = 34.83 µg/ml) and T3 (IC50 = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC50 = 35.44 µg/ml). Compounds T3 (IC50 = 54.01 µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC50 = 54.25 µg/ml). The most potent anticancer activity was shown by compounds T2 (IC50 = 3.84 μM) and T7 (IC50 = 3.25 μM) against HCT116 cell lines as compared to standard 5-FU (IC50 = 25.36 μM).
Unraveling the roles of the reductant and free copper ions in LPMO kinetics
Authors: Stepnov Anton A. , Forsberg Zarah , Sørlie Morten , Nguyen Giang-Son , Wentzel Alexander , Røhr Åsmund K. , Eijsink Vincent G. H. 
Published: January 2021

AbstractBackgroundLytic polysaccharide monooxygenases (LPMOs) are monocopper enzymes that catalyze oxidative depolymerization of industrially relevant crystalline polysaccharides, such as cellulose, in a reaction that depends on an electron donor and O2or H2O2. While it is well known that LPMOs can utilize a wide variety of electron donors, the variation in reported efficiencies of various LPMO-reductant combinations remains largely unexplained.ResultsIn this study, we describe a novel two-domain cellulose-active family AA10 LPMO from a marine actinomycete, which we have used to look more closely at the effects of the reductant and copper ions on the LPMO reaction. Our results show that ascorbate-driven LPMO reactions are extremely sensitive to very low amounts (micromolar concentrations) of free copper because reduction of free Cu(II) ions by ascorbic acid leads to formation of H2O2, which speeds up the LPMO reaction. In contrast, the use of gallic acid yields steady reactions that are almost insensitive to the presence of free copper ions. Various experiments, including dose–response studies with the enzyme, showed that under typically used reaction conditions, the rate of the reaction is limited by LPMO-independent formation of H2O2resulting from oxidation of the reductant.ConclusionThe strong impact of low amounts of free copper on LPMO reactions with ascorbic acid and O2, i.e. the most commonly used conditions when assessing LPMO activity, likely explains reported variations in LPMO rates. The observed differences between ascorbic acid and gallic acid show a way of making LPMO reactions less copper-dependent and illustrate that reductant effects on LPMO action need to be interpreted with great caution. In clean reactions, with minimized generation of H2O2, the (O2-driven) LPMO reaction is exceedingly slow, compared to the much faster peroxygenase reaction that occurs when adding H2O2.