bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coenzyme Q10 inhibits RANKL‐induced osteoclastogenesis by regulation of mitochondrial apoptosis and oxidative stress in RAW264.7 cells
Authors: Zheng Delu , Cui Chenli , Shao Chen , Wang Yanqiu , Ye Chengsong , Lv Gaoyou 
Published: March 2021

AbstractCoenzyme Q10 (CoQ10) has been reported to improve bone density and the number of trabeculae in postmenopausal osteoporosis, but the mechanism remains to be elucidated. We aimed to investigate the effects of CoQ10 on receptor activator of NF‐κB ligand (RANKL)‐induced osteoclastogenesis and the underlying molecular mechanisms. RAW264.7 cells were treated with different concentrations of RANKL to differentiate into osteoclasts, and then these cells were treated with different concentrations of CoQ10 with or without H2O2. Tartrate‐resistant acid phosphatase staining was performed to detect osteoclasts. Cell viability was tested by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, cell apoptosis was examined by flow cytometry, and the effects of CoQ10 on protein and messenger RNA expression of mitochondrial apoptosis‐associated proteins and osteoclast marker proteins were measured by quantitative reverse transcription polymerase chain reaction and western blot, respectively. Furthermore, enzyme‐linked immunosorbent assay was conducted to analyze the activities of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). RANKL significantly induced osteoclastogenesis in RAW264.7 cells, with the greatest efficiency at 50 ng/ml. CoQ10 had no significant effects on cell viability but it significantly increased the percentages of cell apoptosis. Mechanically, CoQ10 statistically decreased the levels of Bcl‐2 and cytochrome C in mitochondria and upregulated the levels of Bax, cleaved caspase 3, and cytochrome C in the cytoplasm. Moreover, CoQ10 significantly decreased RANKL‐induced osteoclastogenesis regardless of exposure to H2O2. In addition, CoQ10 statistically reduced MDA activity and elevated the activities of SOD and CAT, as well as the expression of oxidative stress‐related proteins. CoQ10 may inhibit RANKL‐induced osteoclastogenesis by regulation of mitochondrial apoptosis and oxidative stress in RAW264.7 cells.
STAT3 activation in microglia exacerbates hippocampal neuronal apoptosis in diabetic brains
Authors: Yun Jang‐Hyuk , Lee Da‐Hye , Jeong Han‐Seok , Kim Hye Sun , Ye Sang‐Kyu , Cho Chung‐Hyun 
Published: March 2021

AbstractDiabetes mellitus (DM) characterized by hyperglycemia leads to a variety of complications, including cognitive impairment or memory loss. The hippocampus is a key brain area for learning and memory and is one of the regions that is most sensitive to diabetes. However, the pathogenesis of diabetic neuronal lesion is not yet completely understood. We focused on the association of microglia activation and brain lesions in diabetes. In this study, we investigated whether and how signal transducer and activator of transcription 3 (STAT3) activation in microglia affects neuronal lesions in diabetic brains. Using a streptozotocin‐induced type 1 DM model, we showed enhanced hippocampal neuronal apoptosis that was associated with increased STAT3 activation. We found that hyperglycemia increased the expression of inflammatory cytokines such as interferon‐γ (IFN‐γ) and interleukin‐6, in the diabetic hippocampus. In particular, IFN‐γ induced autocrine activation of microglia, and STAT3 activation is important for this process. We also demonstrated that STAT3 activation in microglia increased tumor necrosis factor‐α (TNF‐α) expression; subsequently, TNF‐α increased neuronal apoptosis by increasing reactive oxygen species (ROS) levels in the neuronal cells. We also took advantage of mice lacking STAT3 in microglia and demonstrated that depletion of microglial STAT3 reduced neuronal apoptosis in the diabetic hippocampus. Taken together, these results suggest that STAT3 activation in microglia plays an important role in hyperglycemia‐induced neuronal apoptosis in the diabetic hippocampus and provide a potential therapeutic benefit of STAT3 inhibition in microglia for preventing diabetic neuronal lesions.
MOG antibody‐positive cerebral cortical encephalitis: Two case reports and literature review
Authors: Tian Fei , Liu Xuejun , Yang Chengqing , Wang Bingbing , Song Zhenfeng , Zhang Ying 
Published: March 2021

AbstractObjectiveTo investigate the clinical and MRI features of myelin oligodendrocyte glycoprotein (MOG) antibody‐positive cerebral cortical encephalitis.MethodsTo summarize the clinical manifestations, magnetic resonance imaging (MRI) features, and diagnosis and treatment of two children diagnosed with MOG antibody‐positive cortical encephalitis in our hospital, and to analyze all of the literature on MOG antibody‐positive associated cerebral cortical encephalitis published in the last 10 years.ResultsA total of 24 patients, 20 adults, and 4 children were included. The main symptoms of all observed patients were as follows: seizures 20/24 (83%), headache 18/24 (75%), fever 13/24 (54%), and increased cell number in cerebrospinal fluid 22/24 (92%). The main radiological sign was enhanced FLAIR signal in cortical 24/24 (100%), including enhanced fluid‐attenuated inversion recovery (FLAIR) signal in unilateral cortical 20/24 (83%).ConclusionsThe clinical manifestations of MOG antibody‐positive cerebral cortical encephalitis are complex and varied, and long‐term follow‐up is needed to clarify the prognosis and recurrence, providing reference for the clinical treatment.
Functional conservation and divergence of color‐pattern‐related agouti family genes in teleost fishes
Authors: Liang Yipeng , Grauvogl Maximilian , Meyer Axel , Kratochwil Claudius F. 
Published: March 2021

AbstractWhile color patterns are highly diverse across the animal kingdom, certain patterns such as countershading and stripe patterns have evolved repeatedly. Across vertebrates, agouti‐signaling genes have been associated with the evolution of both patterns. Here we study the functional conservation and divergence by investigating the expression patterns of the two color‐pattern‐related agouti‐signaling genes, agouti‐signaling protein 1 (asip1) and agouti‐signaling protein 2b (asip2b, also known as agrp2) in Teleostei. We show that the dorsoventral expression profile of asip1 and the role of the “stripe repressor” asip2b are shared across multiple teleost lineages and uncover a previously unknown association between stripe–interstripe patterning and both asip1 and asip2b expression. In some species, including the zebrafish (Danio rerio), these two genes show complementary and overlapping expression patterns in line with functional redundancy. Our results thus suggest how conserved and novel functions of agouti‐signaling genes might have shaped the evolution of color patterns across teleost fishes.
Germline evaluation of patients undergoing tumor genomic profiling: An academic cancer center’s experience with implementing a germline review protocol
Authors: Stachowiak Samantha , Jacquart Amanda , Zimmermann Michael T. , George Ben , Dong Huaying , Geurts Jennifer L. 
Published: March 2021

AbstractTumor genomic profiling (TGP) has the potential to identify germline variants in addition to its primary use of informing cancer treatment based on genetic alterations within the tumor. However, there are no formal consensus guidelines to identify patients who would be eligible for genetic counseling (GC) and germline testing (GT) testing in patients undergoing TGP. The purpose of this study is to describe an institutionally developed Germline Review Protocol (GRP) to evaluate adult cancer patient cases already undergoing TGP to determine GC referral eligibility. We report on our retrospective experience implementing this protocol into practice wherein 172 patients out of 638 patients reviewed (27%) were recommended for a GC referral over a 17‐month time period. Of those 172 patients recommended for a GC referral, only 34 patients (20%) completed GC and GT. Among patients who received GT, 15 (44%) were positive for at least one pathogenic or likely pathogenic (P/LP) variant, seven patients (21%) were negative and 12 patients (35%) had at least 1 variant of uncertain significance (VUS). The primary reason GC and GT was not completed was because the patient moved to hospice care or was deceased. This is one of the first studies outlining the process and results of a formalized institutional protocol to facilitate patient referrals for GC and GT based on TGP results.
ACE2 models of frequently contacted animals provide clues of their SARS‐CoV‐2 S protein affinity and viral susceptibility
Authors: Ma Cheng , Gong Caixia 
Published: March 2021

AbstractThe outbreak of atypical pneumonia (coronavirus disease 2019 [COVID‐19]) has been a global pandemic and has caused severe losses to the global economy. The virus responsible for COVID‐9, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), has a spike glycoprotein (S protein) that binds angiotensin‐converting enzyme 2 (ACE2) present on host cell membranes to gain entry. Based on the full‐length human ACE2 cryo‐EM structure, we generated homology models of full‐length ACE2 proteins from various species (gorilla, monkey, pig, bovine, sheep, cat, dog, mouse, and rat). Although these ACE2 molecules were found to share similar overall structures, their S–ACE2 interface residues differed. These differences likely result in variations in the ACE2 binding affinities to the SARS‐CoV‐2 S protein. The highest affinities are predicted for human, gorilla, and monkey, while mouse and rat ACE2 are predicted to have the lowest affinities. Cat ACE2 is predicted to have a lower S protein affinity than dog ACE2. Although affinity is not the only factor that affects viral susceptibility, it is one of the most important factors. Thus, we believe that care should be taken with these animals to prevent the spread of SARS‐CoV‐2 among animal and human populations.
Outcomes among 10,314 hospitalized COVID‐19 patients at a tertiary care government hospital in Delhi, India
Authors: Malhotra Vikas , Basu Saurav , Sharma Nandini , Kumar Suresh , Garg Sandeep , Dushyant Kumar , Borle Amod 
Published: March 2021

AbstractA significant proportion of patients with coronavirus disease 2019 (COVID‐19) require timely hospitalization to reduce the risk of complications and mortality. We describe the trends of the age and gender stratified outcomes among hospitalized COVID‐19 patients with moderate to severe illness at the largest dedicated tertiary care COVID‐19 government hospital in New Delhi, India. A retrospective cohort study through secondary data analysis from in‐patient hospital data of patients admitted from April 1 to November 15, 2020 was conducted. The data of 10,314 laboratory‐confirmed patients with COVID‐19 was analyzed, of which 8899 (86.28%) were discharged after recovery, and 1415 (13.72%) died. The mean (SD) age of the hospitalized patients was 46.43 (18.74) years (n = 10,309) including 6031 (58.50%) male and 4278 (41.50%) female patients (n = 10,309). On bivariate analysis, increasing age was associated with significantly higher odds of mortality in both gender (p < .001). The mortality rate in female patients was lower (11.92%) compared with male patients (15.75%) (p = .675). However, elderly women had the highest odds of mortality (p < .001), indicating the possible role of delayed health seeking behavior, secondary to familial, and social neglect. Mortality in the patients with COVID‐19 also occurred early after admission suggesting rapid deterioration, delayed reporting by patients, or their late referral from other health facilities. However, the overall statewide recovery rate showed steady improvement since the onset of the pandemic. In contrast, the recovery rate among the moderate‐severe cases that were hospitalized at this tertiary care center during the same period reflected a lower nonspecific zigzag pattern indicating limited effectiveness of the COVID‐19 treatment regimens.
pT3 N0 Laryngeal Squamous Cell Carcinoma: Oncologic Outcomes and Prognostic Factors of Surgically Treated Patients
Authors: Mattioli Francesco , Fermi Matteo , Molinari Giulia , Capriotti Vincenzo , Melegari Gabriele , Bertolini Federica , D'Angelo Elisa , Tirelli Giancarlo , Presutti Livio 
Published: March 2021

Objectives/HypothesisTo assess the disease control, survival rates, and prognostic factors of exclusive surgical treatment for patients with pT3 N0 laryngeal squamous cell carcinoma (LSCC).Study DesignMulticentric retrospective cohort study.MethodsMulticentric retrospective case series of previously untreated patients with pT3 R0N0 LSCC, who received exclusive surgery between 2011 and 2019. Tumor location; subsite involvement; grading; and lymphatic, vascular, and perineural invasion were reported. Overall survival (OS), disease‐specific survival (DSS), and disease‐free survival (DFS) were measured.ResultsFifty‐four patients (mean age 67.1; male sex 83.3%; mean follow‐up period 37 months) underwent total laryngectomy (48.1%) or partial laryngectomy (51.9%). Ipsilateral or bilateral neck dissection was performed in 46 (85.2%) cases. Perineural invasion was more frequent in case of supraglottic involvement than glottic involvement (85.7% vs. 14.3%, P = .03). Five (9.3%) patients experienced recurrence (3 local recurrences, 1 nodal recurrence, 1 distant recurrence). Rate of recurrence differed between glottic (0%), supraglottic (80%), and transglottic (20%) tumors (P = .01), with a lower risk yielded by glottic involvement (odds ratio [OR], 0.05, 95% confidence interval [95% CI], 0.01–0.56, P = .01). A higher risk was recorded in case of perineural invasion (OR, 66.0, 95% CI, 1.41–3085.3, P = .03). The OS, DSS, and DFS were 79.6%, 96.3%, and 90.7%, without differences regarding the type of surgery. The DFS was lower in case of supraglottic involvement when compared to purely glottic LSCC (83.9% vs. 100%, P = 0.02).ConclusionsExclusive surgery is a safe option for patients with pT3 R0N0 LSCC. Adjuvant treatments or closer follow‐up monitoring might be considered in case of supraglottic involvement or perineural invasion.Level of Evidence4 Laryngoscope, 131:2262–2268, 2021
Improving peer‐review by developing reviewers' feedback literacy
Authors: Chong Sin Wang 
Published: March 2021

Key points
There is a need to train journal peer reviewers to provide professional, constructive, and actionable feedback: i.e., develop their feedback literacy.
Journals and publishers can improve the way they support peer reviewers' feedback literacy by raising awareness and providing guidance and exemplars of good practice.
Existing online peer‐review training resources developed by major publishers only focus on content of feedback but neglect the socio‐emotional aspect of feedback.
Resources to develop peer reviewers' feedback literacy should be formulated by adopting knowledge‐based, skills‐based, and community‐based approaches.
N6‐Methyladenosine (m6A) readers are dysregulated in renal cell carcinoma
Authors: von Hagen Felix , Gundert Larissa , Strick Alexander , Klümper Niklas , Schmidt Doris , Kristiansen Glen , Tolkach Yuri , Toma Marieta , Ritter Manuel , Ellinger Jörg 
Published: March 2021

AbstractN6‐Methyladenosine (m6A) is the most common modification of messenger RNA (mRNA) in mammals. It critically influences RNA metabolism and plays an essential role in virtually all types of bioprocesses including gene expression, tissue development, self‐renewal and differentiation of stem cells, stress response and circadian clock control. It plays a crucial role in carcinogenesis and could be used as a prognostic and a diagnostic tool and as a target for new anticancer therapies. m6A modification is dynamically and reversibly regulated by three types of proteins. Methyltransferases, so‐called “writers” add a methyl group to the adenosine, which can be removed by demethylases, also called “erasers.” m6A‐specific RNA‐binding proteins, from here on referred to as “readers,” preferentially bind to the m6A site and mediate biological functions, such as translation, splicing or decay of RNA. In this study, we examined the expression of the six m6A readers HNRNPA2B1, HNRNPC, YTHDC1 and YTHDF1‐3 in clear cell renal carcinoma (ccRCC). We show that on mRNA level the expression of all six m6A readers is significantly downregulated compared to normal renal tissue and on protein level five out of six readers are dysregulated. Lower levels of some m6A readers are correlated with advanced stage and grade as well as associated with a shorter overall, progression‐free and cancer‐specific survival. In summary, we could show that m6A readers are dysregulated in ccRCC and might therefore act as a tumor marker, could give further information on the individual prognosis and be a target of innovative cancer therapy.
Nonlinear modulation ofCOVID‐19 transmission by climate conditions
Authors: Gao Meng , Zhou Qiming , Yang Xian , Li Qingxiang , Zhang Shiqing , Yung Ken Kin Lam , Guo Yike 
Published: March 2021

AbstractCOVID‐19 is spreading rapidly worldwide, posing great threats to public health and economy. This study aims to examine how the transmission of COVID‐19 is modulated by climate conditions, which is of great importance for better understanding of the seasonal feature of COVID‐19. Constrained by the accurate observations we can make, the basic reproduction numbers (R0) for each country were inferred and linked to temperature and relative humidity (RH) with statistical analysis. UsingR0as the measure of COVID‐19 transmission potential, we find stronger transmission of COVID‐19 under mildly warm (0°C <T< 20°C) and humid (RH > 60%) climate conditions, while extremely low (T< −2°C) and high (T> 20°C) temperature or a dry climate (RH < 60%) weakens transmission. The established nonlinear relationships between COVID‐19 transmission and climate conditions suggest that seasonal climate variability may affect the spread and severity of COVID‐19 infection, and temperate coastal regions with mildly warm and humid climate would be susceptible to large‐scale outbreaks.
Anti‐Obesity Effect ofT. ChebulaFruit Extract on High Fat Diet Induced Obese Mice: A Possible Alternative Therapy
Authors: Subramanian Gowtham , Shanmugamprema Deepankumar , Subramani Ramya , Muthuswamy Karthi , Ponnusamy Vinithra , Tankay Kalpana , Velusamy Thirunavukkarasu , Krishnan Vasanth , Subramaniam Selvakumar 
Published: March 2021

AbstractOccurrence of obesity and its associated metabolic disorders continues to escalate. The present study evaluates the anti‐obesity effects of ethanolic fruit extract ofTerminalia chebula(EETC) on high fat diet induced obese mice. The bioactive compounds present in the EETC is evaluated by Fourier‐transform infrared (FT‐IR), Gas chromatography‐mass spectrometry (GC‐MS), and Liquid chromatography‐mass spectrometry (LC‐MS) analysis. The effects of EETC on energy intake, glucose tolerance, and various biochemical parameters were analyzed using laboratory mice. Relative gene expression of Fatty acid synthase (FAS), Peroxisome proliferator‐activated receptors α (PPARα), Carnitine palmitoyltransferase‐1 (CPT‐1), Tumor necrosis factor alpha (TNF‐α) as well as Interleukin 6 (IL‐6) were analyzed in liver and adipose tissues. The findings reveal the hypolipidemic and anti‐obesity potential of EETC on high fat fed obese mice. EETC exerts its anti‐obesity effects by suppressing lipogenesis through reduction in lipogenic enzyme (FAS) expression, increased fatty acid oxidation via PPARα and CPT‐1 and by triggering the anti‐inflammatory responses. To our knowledge, this is the first report of the effect of EETC on PPARα and CPT‐1 in in vivo.
Superoxide free radical spin‐lattice relaxivity: A quench‐assisted MR study
Authors: MacKinnon Martin J. , Berkowitz Bruce A. , Shih Yen‐Yu Ian 
Published: March 2021

PurposeQuEnch‐assiSTed (QUEST) MRI provides a unique biomarker of excessive production of paramagnetic free radicals (oxidative stress) in vivo. The contribution from superoxide, a common upstream species found in oxidative stress‐based disease, to the QUEST metric is unclear. Here, we begin to address this question by measuring superoxide spin‐lattice relaxivity (r1) in phantoms.MethodsStable superoxide free radicals were generated in water phantoms of potassium superoxide (. To measure r1, 1/T1 of different concentration solutions of KO2 in the presence and absence of the antioxidant superoxide dismutase were measured. The 1/T1 confounding factors including acquisition sequence, pH, and water source were also evaluated.ResultsThe T1‐weighted signal intensity increased with KO2 concentration. No contribution from pH, or reaction products other than superoxide, noted on 1/T1. Superoxide r1 was measured to be 0.29 mM−1 s−1, in agreement with that reported for paramagnetic molecular oxygen and nitroxide free radicals.ConclusionOur first‐in‐kind measurement of superoxide free radical r1 suggests a detection sensitivity of QUEST MRI on the order of tens of μM, within the reported level of free radical production during oxidative stress in vivo. Similar studies for other common free radicals are needed.
Ultrashort echo time Cones double echo steady state (UTE‐Cones‐DESS) for rapid morphological imaging of short T2 tissues
Authors: Jang Hyungseok , Ma Yajun , Carl Michael , Jerban Saeed , Chang Eric Y. , Du Jiang 
Published: March 2021

PurposeIn this study, we aimed to develop a new technique, ultrashort echo time Cones double echo steady state (UTE‐Cones‐DESS), for highly efficient morphological imaging of musculoskeletal tissues with short T2s. We also proposed a novel, single‐point Dixon (spDixon)‐based approach for fat suppression.MethodsThe UTE‐Cones‐DESS sequence was implemented on a 3T MR system. It uses a short radiofrequency (RF) pulse followed by a pair of balanced spiral‐out and spiral‐in readout gradients separated by an unbalanced spoiling gradient in‐between. The readout gradients are applied immediately before or after the RF pulses to achieve a UTE image (S+) and a spin/stimulated echo image (S−). Weighted echo subtraction between S+ and S− was performed to achieve high contrast specific to short T2 tissues, and spDixon was applied to suppress fat by using the intrinsic complex signal of S+ and S−. Six healthy volunteers and five patients with osteoarthritis were recruited for whole‐knee imaging. Additionally, two healthy volunteers were recruited for lower leg imaging.ResultsThe UTE‐Cones‐DESS sequence allows fast volumetric imaging of musculoskeletal tissues with excellent image contrast for the osteochondral junction, tendons, menisci, and ligaments in the knee joint as well as cortical bone and aponeurosis in the lower leg within 5 min. spDixon yields efficient fat suppression in both S+ and S− images without requiring any additional acquisitions or preparation pulses.ConclusionThe rapid UTE‐Cones‐DESS sequence can be used for high contrast morphological imaging of short T2 tissues, providing a new tool to assess their association with musculoskeletal disorders.