bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attitude is everything: keep probe pitch neutral during side‐fire prostate biopsy. A simulator study
Authors: Zhang Zhou , Lampotang Samsun , Yu Yichao , Acar Yahya A. , Wakim Jonathan , Mei Vincent , Ahmad Ardalan E. , Shenot Patrick , Lee Jason , Perlis Nathan , Moy Louis , Johnson William T. , DeStephens Anthony , Bigos Andre K. , Lizdas David E. , Stringer Thomas 
Published: May 2021

ObjectivesTo develop and validate on a simulator a learnable technique to decrease deviation of biopsied cores from the template schema during freehand, side‐fire systematic prostate biopsy (sPBx) with the goal of reducing prostate biopsy (PBx) false‐negatives, thereby facilitating earlier sampling, diagnosis and treatment of clinically significant prostate cancer.Participants and MethodsUsing a PBx simulator with real‐time three‐dimensional visualization, we devised a freehand, pitch‐neutral (0°, horizontal plane), side‐fire, transrectal ultrasonography (TRUS)‐guided sPBx technique in the left lateral decubitus position. Thirty‐four trainees on four Canadian and US urology programmes learned the technique on the same simulator, which recorded deviation from the intended template location in a double‐sextant template as well as the TRUS probe pitch at the time of sampling. We defined deviation as the shortest distance in millimeters between a core centre and its intended template location, template deviation as the mean of all deviations in a template, and mastery as achieving a template deviation ≤5.0 mm.ResultsAll results are reported as mean ± sd. The mean absolute pitch and template deviation before learning the technique (baseline) were 8.2 ± 4.1° and 8.0 ± 2.7 mm, respectively, and after mastering the technique decreased to 4.5 ± 2.7° (P = 0.001) and 4.5 ± 0.6 mm (P < 0.001). Template deviation was related to mean absolute pitch (P < 0.001) and increased by 0.5 mm on average with each 1° increase in mean absolute pitch. Participants achieved mastery after practising 3.9 ± 2.9 double‐sextant sets. There was no difference in time to perform a double‐sextant set at baseline (277 ± 102 s) and mastery (283 ± 101 s; P = 0.39).ConclusionA pitch‐neutral side‐fire technique reduced template deviation during simulated freehand TRUS‐guided sPBx, suggesting it may also reduce PBx false‐negatives in patients in a future clinical trial. This pitch‐neutral technique can be taught and learned; the University of Florida has been teaching it to all Urology residents for the last 2 years.
The representative agent bias in cost of living indices
Authors: Bandyopadhyay Sutirtha , Ramaswami Bharat 
Published: May 2021

AbstractThe aggregate cost of the living index requires averaging across household indices. But what if the aggregate index was constructed for the “representative” household as is usually done? The paper examines the resulting bias in the Tornqvist index, widely used for constructing superlative indices as well as for the Cobb–Douglas index, which has a similar functional form. We show that the difference between the two consists of a “plutocratic” bias and a “curvature” bias. The former is well known, but the latter has not been recognized earlier. In empirical applications, the curvature bias is small and orders of magnitude smaller than the plutocratic bias. This suggests much of the overall bias would be removed by constructing the representative agent by democratic averages of budget shares.
Angiotensin II augments renal vascular smooth muscle soluble GC expression via an AT1 receptor–forkhead box subclass O transcription factor signalling axis
Authors: Galley Joseph C. , Hahn Scott A. , Miller Megan P. , Durgin Brittany G. , Jackson Edwin K. , Stocker Sean D. , Straub Adam C. 
Published: May 2021

Background and PurposeReduced renal blood flow triggers activation of the renin‐angiotensin‐aldosterone system (RAAS) leading to renovascular hypertension. Renal vascular smooth muscle expression of the NO receptor, soluble GC (sGC), modulates the vasodilator response needed to control renal vascular tone and blood flow. Here, we tested if angiotensin II (Ang II) affects sGC expression via an AT1 receptor‐forkhead box subclass O (FoxO) transcription factor dependent mechanism.Experimental ApproachUsing a murine two‐kidney‐one‐clip (2K1C) renovascular hypertension model, we measured renal artery vasodilatory function and sGC expression. Additionally, we conducted cell culture studies using rat renal pre‐glomerular smooth muscle cells (RPGSMCs) to test the in vitro mechanistic effects of Ang II treatment on sGC expression and downstream function.Key ResultsContralateral, unclipped renal arteries in 2K1C mice showed increased NO‐dependent vasorelaxation compared to sham control mice. Immunofluorescence studies revealed increased sGC protein expression in 2K1C contralateral renal arteries over sham controls. RPGSMCs treated with Ang II caused a significant up‐regulation of sGC mRNA and protein expression as well as downstream sGC‐dependent signalling. Ang II signalling effects on sGC expression occurred through an AT1 receptor and FoxO transcription factor‐dependent mechanism at both the mRNA and protein expression levels.Conclusion and ImplicationsRenal artery smooth muscle, in vivo and in vitro, up‐regulates expression of sGC following RAAS activity. In both cases, up‐regulation of sGC leads to increased downstream cGMP signalling, suggesting a previously unrecognized protective mechanism to improve renal blood flow in the uninjured contralateral renal artery.LINKED ARTICLESThis article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc
Seed ‘primeomics’: plants memorize their germination under stress
Authors: Srivastava Ashish Kumar , Suresh Kumar Jisha , Suprasanna Penna 
Published: May 2021

ABSTRACTSeed priming is a pre‐germination treatment administered through various chemical, physical and biological agents, which induce mild stress during the early phases of germination. Priming facilitates synchronized seed germination, better seedling establishment, improved plant growth and enhanced yield, especially in stressful environments. In parallel, the phenomenon of ‘stress memory’ in which exposure to a sub‐lethal stress leads to better responses to future or recurring lethal stresses has gained widespread attention in recent years. The versatility and realistic yield gains associated with seed priming and its connection with stress memory make a critical examination useful for the design of robust approaches for maximizing future yield gains. Herein, a literature review identified selenium, salicylic acid, poly‐ethylene glycol, CaCl2 and thiourea as the seed priming agents (SPRs) for which the most studies have been carried out. The average priming duration for SPRs generally ranged from 2 to 48 h, i.e. during phase I/II of germination. The major signalling events for regulating early seed germination, including the DOG1 (delay of germination 1)–abscisic acid (ABA)–heme regulatory module, ABA–gibberellic acid antagonism and nucleus–organelle communication are detailed. We propose that both seed priming and stress memory invoke a ‘bet‐hedging’ strategy in plants, wherein their growth under optimal conditions is compromised in exchange for better growth under stressful conditions. The molecular basis of stress memory is explained at the level of chromatin reorganization, alternative transcript splicing, metabolite accumulation and autophagy. This provides a useful framework to study similar mechanisms operating during seed priming. In addition, we highlight the potential for merging findings on seed priming with those of stress memory, with the dual benefit of advancing fundamental research and boosting crop productivity. Finally, a roadmap for future work, entailing identification of SPR‐responsive varieties and the development of dual/multiple‐benefit SPRs, is proposed for enhancing SPR‐mediated agricultural productivity worldwide.
Upregulation of Nogo‐B by hypoxia inducible factor‐1 and activator protein‐1 in hepatocellular carcinoma
Authors: Han Dingding , Yang Penggao , Qin Bo , Ji Guoqing , Wu Yanhua , Yu Long , Zhang Hong 
Published: May 2021

AbstractNogo‐B is an important regulator of tumor angiogenesis. Expression of Nogo‐B is remarkably upregulated in multiple tumor types, especially hepatocellular carcinoma (HCC). Here, we show the transcriptional regulation mechanisms of Nogo‐B in liver cancer. In response to hypoxia, expression of Nogo‐B significantly increased in HCC tissues and cells. The distal hypoxia‐responsive element in the promoter was essential for transcriptional activation of Nogo‐B under hypoxic conditions, which is the specific site for hypoxia inducible factor‐1α (HIF‐1α) binding. In addition, Nogo‐B expression was associated with c‐Fos expression in HCC tissues. Nogo‐B expression was induced by c‐Fos, yet inhibited by a dominant negative mutant A‐Fos. Deletion and mutation analysis of the predicted activator protein‐1 binding sites revealed that functional element mediated the induction of Nogo‐B promoter activity, which was confirmed by ChIP. These results indicate that HIF‐1α and c‐Fos induce the expression of Nogo‐B depending on tumor microenvironments, such as hypoxia and low levels of nutrients, and play a role in upregulation of Nogo‐B in tumor angiogenesis.
Delineating binding potential, stability of Sulforaphane‐N‐acetyl‐cysteine in the active site of histone deacetylase 2 and testing its cytotoxicity against distinct cancer lines through stringent molecular dynamics, DFT and cell‐based assays
Authors: Ganai Shabir Ahmad , Srinivasan Pappu , Rajamanikandan Sundaraj , Shah Basit Amin , Mohan Suma , Gani Mudasir , Padder Bilal Ahmad , Qadri Raies A. , Bhat M. A. , Baba Zahoor Ahmad , Yatoo Manzoor Ahmad 
Published: May 2021

AbstractHistone deacetylase 2 (HDAC2), an isozyme of Class I HDACs has potent imputations in actuating neurodegenerative signaling. Currently, there are sizeable therapeutic disquiets with the use of synthetic histone deacetylase inhibitors in disease management. This strongly suggests the unfulfilled medical necessity of plant substitutes for therapeutic intervention. Sulforaphane‐N‐acetyl‐cysteine (SFN‐N‐acetylcysteine or SFN‐NAC), a sulforaphane metabolite has shown significantly worthier activity against HDACs under in vitro conditions. However, the atomistic studies of SFN‐NAC against HDAC2 are currently lacking. Thus, the present study employed a hybrid strategy including extra‐precision (XP) grid‐based flexible molecular docking, molecular mechanics generalized born surface area (MM‐GBSA), e‐Pharmacophores method, and molecular dynamics simulation for exploring the binding strengh, mode of interaction, e‐Pharmacophoric features, and stability of SFN‐NAC towards HDAC2. Further, the globally acknowledged density functional theory (DFT) study was performed on SFN‐NAC and entinostat individually in complex state with HDAC2. Apart from this, these inhibitors were tested against three distinct cancer cell models and one transformed cell line for cytotoxic activity. Moreover, double mutant of HDAC2 was generated and the binding orientation and interaction of SFN‐NAC was scrutinized in this state. On the whole, this study unbosomed and explained the comparatively higher binding affinity of entinostat for HDAC2 and its wide spectrum cytotoxicity than SFN‐NAC.
3‐O‐trans‐caffeoyloleanolic acid improves acute lung injury via anti‐inflammation and antioxidative stress‐involved PI3K/AKT pathway
Authors: Huang Jianhua , Nong Xueping , Chen Yanling , Zhang Aimei , Chen Lerong 
Published: May 2021

Abstract3‐O‐trans‐caffeoyloleanolic acid (COA) is a pentacyclic triterpenoid compound, with significant anti‐inflammatory effects. In this study, we report the protective effects of COA on lipopolysaccharide (LPS)‐induced acute lung injury (ALI) and explored its mechanism of action. LPS was used to construct in vivo mouse ALI models to observe the effects of COA pretreatment on lung pathology, inflammation, and oxidative stress. In vitro, mouse alveolar macrophages MH‐S cells were cultured and stimulated with LPS to investigate the effects of COA pretreatment on inflammation and oxidative stress. Western blotting was used to investigate the expression of iNOS, TLR4, p‐p65, p‐AKT, and p‐PI3K from in vivo and in vitro samples. The results showed that COA significantly improved lung injury, inhibited neutrophil infiltration, prevented macrophage infiltration, inhibited the release of inflammatory factors, reduced oxidative stress, and down‐regulated the expression of iNOS, TLR4, p‐p65, p‐AKT, and p‐PI3K in ALI mice caused by LPS. In vitro, COA inhibited the release of inflammatory factors, reduced oxidative stress, and down‐regulated the expression of iNOS, TLR4, p‐p65, p‐AKT, and p‐PI3K in MH‐S cells stimulated with LPS. Of interest, the protective effects of COA were significantly attenuated in MH‐S cells pretreated with the PI3K phosphopeptide activator 740Y‐P with no effect on TLR4 expression observed. Taken together, these findings confirm the protective effects of COA on ALI. We further demonstrate that the anti‐inflammation and antioxidant effects of COA are mediated through its effects on PI3K/AKT and potentially TLR4.
Caspase‐3: A primary target for natural and synthetic compounds for cancer therapy
Authors: Yadav Poonam , Yadav Ramakant , Jain Shweta , Vaidya Ankur 
Published: May 2021

AbstractCaspases, a group of protease enzymes (cysteine proteases), exist as inactive zymogens in the cells and execute apoptosis (programmed cell death). Caspase‐3, an executioner caspase, plays an imperative role in apoptosis and becomes a primary target for cancer treatment. A number of analogues of quinazoline, quinazolinone, indoloquinazolines, quinone, naphthoquinones, pyrroloiminoquinones, styrylquinolines, tetheredtetrahydroquinoline, fluoroquinolone, thiosemicarbazones, benzotriazole, pyrimidines, chalcone, and carbazoles have been reported till date, representing caspase‐3 mediated apoptosis for cancer therapy. Simultaneously, plant isolates, including lysicamine, podophyllotoxin, and majoranolide, have also been claimed for caspase‐3‐mediated apoptosis‐induced cytotoxicity. Procaspase‐activating compound‐1 (PAC‐1) is the first FDA approved orphan drug, and its synthetic derivative WF‐208 also showed fascinating caspase‐3 mediated anticancer activity. Till date, a large number of compounds have been reported and patented for their caspase‐3‐mediated cytotoxicity and now scientist is also focusing to introduce new compounds in market to encompass anticancer activity.
Synthesis and evolution of neuroprotective effects of oxymatrine derivatives as anti‐Alzheimer’s disease agents
Authors: Dong Pei‐Liang , Li ZhengQing , Teng Cui‐li , Yin Xin , Cao Xian‐Kai , Han Hua 
Published: May 2021

AbstractWhile screening for natural product scaffolds as potential anti‐Alzheimer's disease (AD), oxymatrine (OMT) was found to relieve symptoms of AD through diminishing death of neuronal cells caused by microglia‐induced inflammation. In this study, 13 derivatives of OMT were synthesized and their neuroprotective effects were evaluated on Aβ1‐42‐induced PC12 cells using MTT method. In addition, the best neuroprotective potencies were obtained with compounds 4, 6e, and 6f, which were selected for evaluation of decrease in IL‐1β and TNF‐α in Aβ1‐42‐treated PC12 cells. Collectively, these data reveal that derivatives 6e and 6f possess the best ability of diminish IL‐1β production and reverse cell damage in all compounds, which are possible to develop as therapeutic agents for AD.
Temporomandibular‐disorder‐related pain as a predictor of severe headaches
Authors: Ashraf Javed , Närhi Matti , Suominen Anna Liisa , Zaproudina Nina , Saxlin Tuomas 
Published: May 2021

AbstractObjectiveThe current study aimed to investigate the association of temporomandibular disorders (TMD)‐related pain with the presence of migraine or tension‐type headaches (TTH) over a follow‐up period of 11 years.MethodsData sets from Finnish national health surveys, the Health 2000 Survey (baseline), and the Health 2011 Survey (follow‐up) were utilized. Study participants are undergoing clinical TMD examination at baseline and answering questions related to the presence of migraine and TTH at follow‐up were included in the study (n = 530). For analyses, the study sample was divided into two data sets: One with those excluded suffering from migraine at baseline (Data set I, n = 345), and the other excluding those having TTH at baseline (Data set II, n = 464).ResultsBased on logistic regression modelling, no consistent association between TMD‐related pain and the presence of migraine was observed, although jTMD associated with elevated estimates for migraine. However, participants with muscle‐related TMD pain (mTMD) at baseline had markedly higher odds for having TTH at follow‐up than participants without mTMD at baseline (OR 2.1, 95% CI 1.2‐3.8). Joint‐related TMD pain (jTMD) at baseline was inversely associated with the presence of TTH at follow‐up (OR 0.4, 95% CI 0.1‐1.3).ConclusionContrasting patterns of the associations of TMD‐related pain with different severe headaches point towards a more thorough and systematic research approach are needed to understand the mechanisms behind these associations.
The use of biologics in food allergy
Authors: Fiocchi Alessandro , Vickery Brian P. , Wood Robert A. 
Published: May 2021

AbstractBackgroundFood allergy continues to pose problems due to its increased frequency and its increasingly high severity. In this context, alongside the traditional avoidance strategies of allergenic foods and desensitization through the cautious progression of exposure to foods in the context of oral immunotherapy (OIT), alternative strategies have made their way in the last decades. We review the possibilities of intervention in food allergy with the use of biological drugs capable of interfering with the synthesis of IgE, with their mechanisms of action, or with complex biological mechanisms that lead to the establishment of a food allergy.MethodsRepeated Entrez PubMed searches using the template algorithm “Food allergy” and “biologics” or “Omalizumab” or “Dupilumab” or “milk desensitization” or “oral tolerance induction” or “oral immunotherapy” or “Etokimab” or “Tezepelumab” or “Quilizumab” or “Ligelizumab” or “Tralokinumab” or “Nemolizumab” or “Mepolizumab” or “Reslizumab” or “Benralizumab”. The authors’ clinical experience in paediatric allergy units of University hospitals was also drawn upon.ResultsThe landscape in this context has changed dramatically over the past 10 years. We have acquired knowledge mainly on the effect of different types of anti‐IgE treatments in poliallergic patients with food allergy, and in patients treated with OIT. However, other mediators are being targeted by specific biologic treatments. Among them, the alarmins Il‐33 and TSLP, IL‐4 and IL‐13, eosinophil‐related molecules as IL‐6, IL‐8, IL‐10, IL‐12, and mostly IL‐5, and integrins involved in the pathogenesis of eosinophilic gastrointestinal diseases (EGIDs), as SIGLEC‐8.ConclusionsThe ever‐better knowledge of the mechanisms of food allergy allowing these developments will improve not only the perspective of patients with the most serious immediate food allergies such as anaphylaxis, but also those of patients with related diseases such as atopic dermatitis, eosinophilic esophagitis, and EGIDs. Biologics are also intended to complement OIT strategies that have developed over the years.
Establishment of a novel double-monoclonal antibody sandwich enzyme-linked immunosorbent assay (ELISA): tool for human B7-H4 detection in autoimmune diseases
Authors: Ding Sisi , Zhou Hengxin , Gu Yanzheng , Shen Yu , Zhang Li , Zhao Huayang , Wu Jian , Zhang Xueguang , Chang Xin , Liu Cuiping 
Published: May 2021

SummaryB7-H4, one of the immunoregulatory proteins, plays an inhibitory role by inhibiting T cell proliferation and cytokine production. Nevertheless, the significance of soluble B7-H4 (sB7-H4) in autoimmune diseases is unclear. In our study, we developed two novel mouse anti-human B7-H4 monoclonal antibodies (mAbs) (clones 8D4 and 7E1) with utilities for flow cytometry, immunoblotting and immunofluorescence. We characterized 7E1 as a functional antibody with antagonistic activity, which could promote T cell proliferation and regulate cytokine production. Furthermore, based on the different epitope specificities, we established a novel enzyme-linked immunosorbent assay (ELISA) which could detect sB7-H4 sensitively and specifically. Using this ELISA kit, sB7-H4 was observed in a high proportion of autoimmune diseases patients. We found that the levels of sB7-H4 were significantly higher in patients with systemic lupus erythematosus (SLE), type I diabetes (T1D) and Graves’ disease (GD). Together, sB7-H4 in human serum is regarded not only as a regulator of T cell activation but may also be a diagnostic marker of autoimmune diseases.
Spinocerebellar ataxia type 2 from an evolutionary perspective: Systematic review and meta‐analysis
Authors: Sena Lucas Schenatto , dos Santos Pinheiro Jordânia , Hasan Ali , Saraiva‐Pereira Maria Luiza , Jardim Laura Bannach 
Published: May 2021

AbstractDominant diseases due to expanded CAG repeat tracts, such as spinocerebellar ataxia type 2 (SCA2), are prone to anticipation and worsening of clinical picture in subsequent generations. There is insufficient data about selective forces acting on the maintenance of these diseases in populations. We made a systematic review and meta‐analysis on the effect of the CAG length over age at onset, instability of transmissions, anticipation,de novoor sporadic cases, fitness, segregation of alleles, and ancestral haplotypes. The correlation between CAG expanded and age at onset was r2 = 0.577, and transmission of the mutant allele was associated with an increase of 2.42 CAG repeats in the next generation and an anticipation of 14.62 years per generation, on average. Onede novoand 18 sporadic cases were detected. Affected SCA2 individuals seem to have more children than controls. The expanded allele was less segregated than the 22‐repeat allele in children of SCA2 subjects. Several ancestral SCA2 haplotypes were published. Data suggest that SCA2 lineages may tend to disappear eventually, due to strong anticipation phenomena. Whether or not the novel cases come from common haplotypes associated with a predisposition to further expansions is a question that needs to be addressed by future studies.
PPP3CA truncating variants clustered in the regulatory domain cause early‐onset refractory epilepsy
Authors: Panneerselvam Sugi , Wang Julia , Zhu Wenmiao , Dai Hongzheng , Pappas John G. , Rabin Rachel , Low Karen J. , Rosenfeld Jill A. , Emrick Lisa , Xiao Rui , Xia Fan , Yang Yaping , Eng Christine M. , Anderson Anne , Chau Vann , Soler‐Alfonso Claudia , Streff Haley , Lalani Seema R. , Mercimek‐Andrews Saadet ,   Undiagnosed Diseases Network,   the DDD Study, Bi Weimin 
Published: May 2021

AbstractPPP3CA encodes the catalytic subunit of calcineurin, a calcium‐calmodulin‐regulated serine–threonine phosphatase. Loss‐of‐function (LoF) variants in the catalytic domain have been associated with epilepsy, while gain‐of‐function (GoF) variants in the auto‐inhibitory domain cause multiple congenital abnormalities. We herein report five new patients with de novo PPP3CA variants. Interestingly, the two frameshift variants in this study and the six truncating variants reported previously are all located within a 26‐amino acid region in the regulatory domain (RD). Patients with a truncating variant had more severe earlier onset seizures compared to patients with a LoF missense variant, while autism spectrum disorder was a more frequent feature in the latter. Expression studies of a truncating variant showed apparent RNA expression from the mutant allele, but no detectable mutant protein. Our data suggest that PPP3CA truncating variants clustered in the RD, causing more severe early‐onset refractory epilepsy and representing a type of variants distinct from LoF or GoF missense variants.