bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncogenic Chromatin Modifier KAT2A Activates MCT1 to Drive the Glycolytic Process and Tumor Progression in Renal Cell Carcinoma
Authors: Guo Yuanyuan , Liu Beibei , Liu Yihan , Sun Wei , Gao Wuyue , Mao Shilong , Chen Li 
Published: June 2021

ObjectivesThis study aims to investigate the underlying mechanisms of KAT2A/MCT1 axis in renal cell carcinoma (RCC), providing potential therapeutic targets.MethodsWe obtained the expression data of KAT2A and MCT1 from The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) and International Cancer Genome Consortium (ICGC) databases. Differential analysis was conducted via the limma package. The CCK8 assay, soft agar assay, clone formation assay, and patients-derived organoid models were used to detect cell growth. The transwell and wound-healing assays were utilized to detect cell migration. The in vitro and in vivo assays were further conducted to assess the oncogenic roles of KAT2A. The transcriptome sequencing and chromatin immunoprecipitation (ChIP) sequencing were conducted to screen KAT2A downstream targets. The dose-effect curves were used to detect the 50% inhibiting concentration (IC50) of AZD3965. Data analysis was performed in the Graphpad Prism (Version 8.3.0) and R software (Version 3.6.1).ResultsOur study found that KAT2A was highly expressed in RCC versus normal samples. Prognostic analysis indicated that a high KAT2A was an independent biomarker and associated with poor survival outcomes. KAT2A could promote RCC proliferation and distal metastasis in vitro and in vivo. Transcriptome analysis and ChIP-seq were combined to find that KAT2A mainly regulated the glycolytic process. Validation and rescue assays revealed that MCT1 was the downstream target of KAT2A, and KAT2A depended on MCT1 to promote RCC malignant phenotypes. Lastly, MCT1 inhibitor (AZD3965) was effective to treat KAT2A-induced RCC progression.ConclusionOur study indicated that KAT2A was an oncogenic chromatin modifier that promotes RCC progression by inducing MCT1 expression. We proposed that MCT1 inhibitor (AZD3965) was useful for suppressing RCC.
Boron-Doped MXenes as Electrocatalysts for Nitrogen Reduction Reaction: A Theoretical Study
Authors: Wang Yuan , Qian Xu , Zheng Guokui , Tian Ziqi , Zhang Qiuju 
Published: June 2021

Electrocatalytic nitrogen reduction reaction (NRR) is a promising and sustainable approach for ammonia production. Since boron as an active center possesses electronic structure similar to that of transition metals withd-orbitals (J. Am. Chem. Soc., 2019, 141 (7), 2884), it is supposed to be able to effectively activate the triple bond in N2. MXenes can be applied as substrates due to the large specific surface area, high conductivity, and tunable surface composition. In this work, the catalytic performance of a series of MXenes-supported single boron atom systems (labeled as B@MXenes) has been systematically studied by using density functional theory (DFT). B@Nb4C3O2, B@Ti4N3O2, and B@Ti3N2O2were screened out owing to outstanding catalytic activity with limiting potentials of −0.26, −0.15, and −0.10 V, respectively. Further analysis shows that the unique property of boron that can intensely accept lone pair and back-donate the anti-bond of nitrogen contributes to the activation of inert triple bond. This work provides a new idea for the rational design of NRR catalyst and is of great significance for the future development of nitrogen reduction catalysts.
Combination of Blood Routine Examination and T-SPOT.TB Assay for Distinguishing Between Active Tuberculosis and Latent Tuberculosis Infection
Authors: Luo Ying , Tang Guoxing , Yuan Xu , Lin Qun , Mao Liyan , Song Huijuan , Xue Ying , Wu Shiji , Ouyang Renren , Hou Hongyan , Wang Feng , Sun Ziyong 
Published: June 2021

BackgroundDistinguishing between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging.MethodsBetween 2013 and 2019, 2,059 (1,097 ATB and 962 LTBI) and another 883 (372 ATB and 511 LTBI) participants were recruited based on positive T-SPOT.TB (T-SPOT) results from Qiaokou (training) and Caidian (validation) cohorts, respectively. Blood routine examination (BRE) was performed simultaneously. Diagnostic model was established according to multivariate logistic regression.ResultsSignificant differences were observed in all indicators of BRE and T-SPOT assay between ATB and LTBI. Diagnostic model built on BRE showed area under the curve (AUC) of 0.846 and 0.850 for discriminating ATB from LTBI in the training and validation cohorts, respectively. Meanwhile, TB-specific antigens spot-forming cells (SFC) (the larger of early secreted antigenic target 6 and culture filtrate protein 10 SFC in T-SPOT assay) produced lower AUC of 0.775 and 0.800 in the training and validation cohorts, respectively. The diagnostic model based on combination of BRE and T-SPOT showed an AUC of 0.909 for differentiating ATB from LTBI, with 78.03% sensitivity and 90.23% specificity when a cutoff value of 0.587 was used in the training cohort. Application of the model to the validation cohort showed similar performance. The AUC, sensitivity, and specificity were 0.910, 78.23%, and 90.02%, respectively. Furthermore, we also assessed the performance of our model in differentiating ATB from LTBI with lung lesions. Receiver operating characteristic analysis showed that the AUC of established model was 0.885, while a threshold of 0.587 yield a sensitivity of 78.03% and a specificity of 85.69%, respectively.ConclusionsThe diagnostic model based on combination of BRE and T-SPOT could provide a reliable differentiation between ATB and LTBI.
A Multiplex and Colorimetric Reverse Transcription Loop-Mediated Isothermal Amplification Assay for Sensitive and Rapid Detection of Novel SARS-CoV-2
Authors: Juscamayta-López Eduardo , Valdivia Faviola , Horna Helen , Tarazona David , Linares Liza , Rojas Nancy , Huaringa Maribel 
Published: June 2021

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major threat to public health. Rapid molecular testing for convenient and timely diagnosis of SARS-CoV-2 infections represents a challenge that could help to control the current pandemic and prevent future outbreaks. We aimed to develop and validate a multiplex and colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using lyophilized LAMP reagents for sensitive and rapid detection of SARS-CoV-2. LAMP primers were designed for a set of gene targets identified by a genome-wide comparison of viruses. Primer sets that showed optimal features were combined into a multiplex RT-LAMP assay. Analytical validation included assessment of the limit of detection (LoD), intra- and inter-assay precision, and cross-reaction with other respiratory pathogens. Clinical performance compared to that of real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was assessed using 278 clinical RNA samples isolated from swabs collected from individuals tested for COVID-19. The RT-LAMP assay targeting the RNA-dependent RNA polymerase (RdRp), membrane (M), and ORF1ab genes achieved a comparable LoD (0.65 PFU/mL, CT=34.12) to RT-qPCR and was 10-fold more sensitive than RT-qPCR at detecting viral RNA in clinical samples. Cross-reactivity to other respiratory pathogens was not observed. The multiplex RT-LAMP assay demonstrated a strong robustness and acceptable intra- and inter-assay precision (mean coefficient of variation, 4.75% and 8.30%). Diagnostic sensitivity and specificity values were 100.0% (95% CI: 97.4–100.0%) and 98.6% (95% CI: 94.9–99.8%), respectively, showing high consistency (Cohen’s kappa, 0.986; 95% CI: 0.966–1.000; p&lt;0.0001) compared to RT-qPCR. The novel one-step multiplex RT-LAMP assay is storable at room temperature and showed similar diagnostic accuracy to conventional RT-qPCR, while being faster (&lt;45 min), simpler, and cheaper. The new assay could allow reliable and early diagnosis of SARS-CoV-2 infections in primary health care. It may aid large-scale testing in resource-limited settings, especially if it is integrated into a point-of-care diagnostic device.
Implementing a Hybrid Summer Transition Program
Authors: Gibson Stephen M. , Brinkley Kendra , Griggs Lauren A. , James Briana N. , Smith Mychal , Schwitzerlett Mark , Waller LaChelle M. , Hargraves Rosalyn Hobson 
Published: June 2021

The mission of the Virginia Commonwealth University Louis Stokes Alliance for Minority Participation (VCU LSAMP) program is to increase the retention and graduation rates of students from underrepresented racial and ethnic groups in science, technology, engineering, and mathematics (STEM) majors and those who matriculate into graduate programs. VCU LSAMP offers a hybrid summer transition program (HSTP) focused on facilitating the high school to college and two-year to four-year college transition process for students majoring in STEM disciplines. The goals of the program are to 1) build community among a cohort of students, 2) orient students to VCU, 3) prepare students for the academic rigors of their first year in a STEM discipline at VCU, 4) expose students to opportunities and careers in STEM, 5) engage them in the VCU LSAMP program, and 6) provide financial support. Five distinct components of the VCU HSTP are 1) a six-week online summer component, 2) a 1 week on-campus orientation, 3) a Design Project Challenge, 4) a transfer student track, and 5) an academic year component. Evaluation data reveals that the HSTP assisted participants with adjustment to the college schedule and setting, facilitated the formation of study groups, and increased overall motivation to graduate. The online courses helped familiarize students with both the academic topics in their chemistry and mathematics classes and the behaviors and norms of STEM majors. On average, participants in the HSTP had higher retention (85%) and graduation (73%) rates when compared with their peers (81% and 64%, respectively). Furthermore, those students who complete the online classes’ requirements had a higher probability of receiving a grade of B or better in their first mathematics or chemistry class.
Expression and Prognosis Analysis of SUMOylation Regulators in Oral Squamous Cell Carcinoma Based on High-Throughput Sequencing
Authors: Meng Yutong , Li Xiaozhi 
Published: June 2021

IntroductionOral squamous cell carcinoma (OSCC) originates from oral mucosal epithelial cells, accounting for more than 90% of oral cancers. The relationship between the expression and prognostic role of SUMOylation regulators in OSCC is rarely studied.Materials and methodsThe expression and survival data of OSCC were derived from TCGA and GEO databases. Wilcoxon test was used to determine the differential expression of the SUMOylation regulators. A prognostic model based on SUMOylation regulator-related genes was constructed by Cox regression. Gene set enrichment analysis was applied to predict the potential biological functions that the genes might be involved in.ResultsRANBP2 and SENP6 had the highest SNV frequency. Eleven genes including PIAS3, RANBP2, USPL1, SENP6, SENP2, SENP5, SAE1, UBA2, PIAS4, UBE2I, and SENP3 were highly expressed in OSCC. The prognostic model based on nine SUMOylation-regulated genes (TRIM37, UFM1, FUBP1, CCNT1, FXR1, HMG20A, RANBP3, SPATA5, and DDX23) had a strong ability to predict the prognosis of OSCC.ConclusionThis study might provide targets for prognostic evaluation and targeted therapy of patients with OSCC.
Connecting Metabolism to Mastitis: Hyperketonemia Impaired Mammary Gland Defenses During a Streptococcus uberis Challenge in Dairy Cattle
Authors: Swartz Turner H. , Bradford Barry J. , Mamedova Laman K. 
Published: June 2021

β-hydroxybutyrate (BHB) has been associated with disease incidence in early lactation dairy cattle, but such associations do not demonstrate causation. Therefore, the objective of this study was to examine the effects of BHB during an intramammaryStreptococcus uberischallenge. A secondary objective was to elucidate the mechanisms behind BHB effects on cytokine transcript abundance using the RAW 264.7 cell line. Late lactation multiparous dairy cows (n = 12) were continuously infused intravenously with either BHB to induce hyperketonemia (target concentration: 1.8 mM) or with saline (CON) for 72 h during aS. uberisintramammary challenge. Body temperature, dry matter intake (DMI), milk production, and milkS. uberiscfu were measured daily until one week post-challenge. Blood samples were collected during infusion to assess changes in metabolism (glucose, insulin, glucagon, NEFA, and cortisol) and systemic inflammation (IL-1β and SAA). Mammary biopsies were conducted at 72 h post-challenge to assess transcript abundance of inflammation-associated genes. BHB-infused cows exhibited a delayed febrile response, noted by a lesser vaginal temperature during the final day of infusion, followed by a greater vaginal temperature 6 d post-challenge. Consequently, BHB-infused cows had greaterS. uberiscfu on d 4, 6, and 7 as compared to CON. Accordingly, BHB-infused cows consumed less DM, produced less milk, had reduced blood glucose, and had increased cortisol concentrations, however, no effects were seen on other systemic parameters or transcript abundance of inflammation-related genes in mammary tissue. To elucidate mechanisms behind the impaired immune defenses, RAW 264.7 cells were transfected with a GPR109A siRNA for 24 h and then treated with or without 1.8 mM BHB and challenged or left unchallenged withS. uberisfor an additional 3 h. Transfection with siRNA reducedGpr109aby 75%. Although BHB treatment did not significantly increaseIl10, GPR109A knockdown as compared to the scrambled control reducedIl10by 90% inS. uberischallenged macrophages treated with BHB, suggesting that macrophage immune responses toS. uberiscan be alteredviaa GPR109A-dependent mechanism. Taken together, these data suggest that BHB altered the immune response promoting tolerance towardS. uberisrather than resistance.
PPAR-α Agonist Fenofibrate Prevented Diabetic Nephropathy by Inhibiting M1 Macrophages via Improving Endothelial Cell Function in db/db Mice
Authors: Feng Xiaomeng , Gao Xia , Wang Shuo , Huang Mengxiu , Sun Zhencheng , Dong Hengbei , Yu Haitian , Wang Guang 
Published: June 2021

Background: Diabetic nephropathy (DN) is one of the major diabetic microvascular complications, and macrophage polarization plays a key role in the development of DN. Endothelial cells regulate macrophage polarization. Peroxisome proliferator-activated receptor (PPAR)-α agonists were demonstrated to prevent DN and improve endothelial function. In this study, we aimed to investigate whether PPAR-α agonists prevented DN through regulating macrophage phenotype via improving endothelial cell function.Methods: Eight-week-old male C57BLKS/J db/m and db/db mice were given fenofibrate or 1% sodium carboxyl methylcellulose by gavage for 12 weeks.Results: Db/db mice presented higher urinary albumin-to-creatinine ratio (UACR) than db/m mice, and fenofibrate decreased UACR in db/db mice. Fibrosis and collagen I were elevated in db/db mouse kidneys compared with db/m mouse kidneys; however, they were decreased after fenofibrate treatment in db/db mouse kidneys. Apoptosis and cleaved caspase-3 were enhanced in db/db mouse kidneys compared to db/m mouse kidneys, while fenofibrate decreased them in db/db mouse kidneys. Db/db mice had a suppression of p-endothelial nitric oxide synthase (eNOS)/t-eNOS and nitric oxide (NO), and an increase of angiopoietin-2 and reactive oxygen species (ROS) in kidneys compared with db/m mice, and fenofibrate increased p-eNOS/t-eNOS and NO, and decreased angiopoietin-2 and ROS in db/db mouse kidneys. Hypoxia-inducible factor (HIF)-1α and Notch1 were promoted in db/db mouse kidneys compared with db/m mouse kidneys, and were reduced after fenofibrate treatment in db/db mouse kidneys. Furthermore, the immunofluorescence staining indicated that M1 macrophage recruitment was enhanced in db/db mouse kidneys compared to db/m mouse kidneys, and this was accompanied by a significant increase of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in kidneys and in serum of db/db mice compared with db/m mice. However, fenofibrate inhibited the renal M1 macrophage recruitment and cytokines associated with M1 macrophages in db/db mice.Conclusions: Our study indicated that M1 macrophage recruitment due to the upregulated HIF-1α/Notch1 pathway induced by endothelial cell dysfunction involved in type 2 diabetic mouse renal injury, and PPAR-α agonist fenofibrate prevented DN by reducing M1 macrophage recruitment via inhibiting HIF-1α/Notch1 pathway regulated by endothelial cell function in type 2 diabetic mouse kidneys.
Precision Repetitive Transcranial Magnetic Stimulation Over the Left Parietal Cortex Improves Memory in Alzheimer’s Disease: A Randomized, Double-Blind, Sham-Controlled Study
Authors: Jia Yanli , Xu Luoyi , Yang Kehua , Zhang Yingchun , Lv Xinghui , Zhu Zhenwei , Chen Zheli , Zhu Yunlong , Wei Lili , Li Xia , Qian Mincai , Shen Yuedi , Hu Weiming , Chen Wei 
Published: June 2021

ObjectiveWe aim to study the effect of precision repetitive transcranial magnetic stimulation (rTMS) over the left parietal cortex on the memory and cognitive function in Alzheimer’s disease (AD).MethodsBased on the resting-state functional magnetic resonance imaging, the left parietal cortex site with the highest functional connectivity to the hippocampus was selected as the target of rTMS treatment. Sixty-nine AD patients were randomized to either rTMS or sham treatment (five sessions/week for a total of 10 sessions). The Mini-Mental State Examination (MMSE), 12-Word Philadelphia Verbal Learning Test (PVLT), and Clinical Dementia Rating (CDR) were assessed at baseline and after the last session.ResultsAfter a 2-week treatment, compared to patients in the sham group, those in the rTMS group scored significantly higher on PVLT total score and its immediate recall subscale score. Moreover, in the rTMS group, there were significant improvements after the 2-week treatment, which were manifested in MMSE total score and its time orientation and recall subscale scores, as well as PVLT total score and its immediate recall and short delay recall subscale scores. In the sham group, the PVLT total score was significantly improved.ConclusionThe target site of the left parietal cortex can improve AD patients’ cognitive function, especially memory, providing a potential therapy.
Stroke Severity and Outcomes in Patients With Newly Diagnosed Atrial Fibrillation
Authors: Watanabe Kotaro , Okazaki Shuhei , Kitano Takaya , Sugiyama Shintaro , Ohara Mariko , Kanki Hideaki , Sasaki Tsutomu , Sakaguchi Manabu , Mochizuki Hideki , Todo Kenichi 
Published: June 2021

Background and Purpose: Once a stroke occurs in a patient with atrial fibrillation (AF), it is likely to be severe. Patients with newly diagnosed AF after stroke and those with known AF before stroke have different background characteristics, yet the difference in stroke severity has not been sufficiently evaluated. In the current study, we compared the stroke severity and in-hospital outcomes between these patient groups.Methods: We retrospectively analyzed a database of 196 patients with acute ischemic stroke and AF between January 2010 and October 2019. We divided the patients into two groups: patients with “newly diagnosed AF” and those with “known AF.” We assessed the stroke severity using the National Institutes of Health Stroke Scale (NIHSS) score on admission and in-hospital outcomes using the modified Rankin Scale (mRS) score at discharge.Results: The proportion of newly diagnosed AF was 33% (64/196). There were no differences in age, hypertension, diabetes mellitus, and past history of heart failure between patients with newly diagnosed AF and those with known AF. Patients with newly diagnosed AF were associated with a lower proportion of male sex (male; 50 vs. 67%, p &lt; 0.05), a lower proportion of past history of stroke (12 vs. 35%, p &lt; 0.01), a lower CHA2DS2-VASc score (median [interquartile range]; 3 [2–4] vs. 3.5 [3–5], p &lt; 0.01), and a lower proportion of pre-stroke oral anticoagulation (5 vs. 59%, p &lt; 0.01). There were no differences in the NIHSS score on admission (12 [4–19] vs. 9 [3–19]) or the mRS score at discharge (3 [1–5] vs. 3 [1–5]). After adjustment for relevant covariates, newly diagnosed AF was not associated with the NIHSS score on admission [adjusted common odds ratio (OR), 0.85; 95% confidence interval (CI), 0.45–1.60] or the mRS score at discharge (adjusted common OR, 1.67; 95% CI, 0.88–3.18). After propensity score matching, newly diagnosed AF was not associated with the NIHSS score on admission (adjusted common OR, 0.91; 95% CI, 0.48–1.73) and the mRS score at discharge (adjusted common OR, 1.77; 95% CI, 0.92–3.43).Conclusion: Stroke severity and in-hospital outcomes in patients with newly diagnosed AF did not differ from those in patients with known AF after adjustment for clinically relevant factors. The importance of detection of latent AF and subsequent anticoagulation in preventing severe stroke should be further emphasized.
Frequency of Non-motor Symptoms in Parkinson's Patients With Motor Fluctuations
Authors: Fernandes Mariana , Pierantozzi Mariangela , Stefani Alessandro , Cattaneo Carlo , Bonizzoni Erminio A. , Cerroni Rocco , Mercuri Nicola Biagio , Liguori Claudio 
Published: June 2021

Background: Non-motor symptoms (NMS), including neuropsychiatric, sleep, autonomic, and sensory domains, are an integral aspect of the clinical presentation of Parkinson disease (PD) and affect neurocognitive functioning as well as patients' and caregivers' well-being.Objective: To describe the occurrence of NMS in PD patients with motor fluctuations in real-life condition.Methods: The present study is a secondary analysis of a previous multinational, multicenter, retrospective-prospective cohort observational study (SYNAPSES). Patients with PD diagnosis and motor fluctuations aged ≥18 years were included. Data collected at the baseline visit were used for this study, and descriptive analyzes were conducted to describe the distribution of NMS in motor-fluctuating PD patients distributed according to different clinical characteristics.Results: Of the 1,610 patients enrolled, 1,589 were included for the analysis (978 males and 611 females), with a mean age of 68.4 (SD = 9.6). Most patients had at least one NMS (88.5%). Sleep problems and psychiatric symptoms were the most prevalent NMS in motor fluctuating PD patients in all H and Y stages. Psychiatric disorders were more frequent in older patients and in patients with a larger number of years of PD diagnosis, while sleep problems were more preeminent in younger patients and with inferior disease duration.Conclusions: The present findings further support the high prevalence of NMS in PD patients with motor fluctuations, thus reinforcing the need for assessing them for diagnostic accuracy and for delivering holistic care.