bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of e‐OSPE as compared to traditional OSPE: A pilot study
Authors: Dutta Atanu Kumar , Goswami Kalyan , Murugayan Sathish Babu , Sahoo Sibasish , Pal Amit , Paul Chandramallika , Thallapaneni Sasikala , Biswas Soham 
Published: March 2021

AbstractObjectively Structured Clinical/Practical Examination (OSCE/OSPE) has been the backbone of the assessment system of graduate medical education for over three decades. We have developed an electronic Objectively Structured Practical Examination (e‐OSPE) in Medical Biochemistry using the freely available Google forms to mitigate the academic disruption posed by COVID‐19 pandemic in our resource‐poor setting. Ten e‐OSPE stations created, interlinked, and time‐restricted. Fifty undergraduate students appeared for the e‐OSPE examination on a prefixed date and time. Learner feedback was collected immediately after the completion of the examination. Facilitator feedback was also collected. Students' mean scores in e‐OSPE and traditional OSPE were 78.15% and 74.56%, respectively. Their difference was not statistically significant (paired t‐test two‐tailed p‐value 0.0979). Thus, the results of e‐OSPE are reliable as compared to traditional OSPE. Bland Altman Plot revealed 92% of students had scores that were in the agreeable limit of both traditional OSPE and e‐OSPE. Both the learners and facilitators were in consensus that the online format of e‐OSPE is a good alternative for assessment (0.67 and 0.82); their experience was good (0.72 and 0.92) and conduction was well organized (0.73 and 0.86). Several suggestions were also received to make e‐OSPE even more effective. In conclusion, this pilot study showed e‐OSPE can be an effective alternative to traditional OSPE when “in‐person” evaluation is not possible such as in the current era of COVID‐19 even in resource‐limited settings.
12‐Month outcomes of transcatheter tricuspid valve repair with the PASCAL system for severe tricuspid regurgitation
Authors: Kitamura Mitsunobu , Fam Neil P. , Braun Daniel , Ruf Tobias , Sugiura Atsushi , Narang Akhil , Connelly Kim A. , Ho Edwin , Nabauer Michael , Hausleiter Jörg , Weber Marcel , Nickenig Georg , Davidson Charles J. , Thiele Holger , von Bardeleben Ralph Stephan , Lurz Philipp 
Published: March 2021

AbstractObjectivesWe investigated the durability of tricuspid regurgitation (TR) reduction and the clinical outcomes through 12 months after transcatheter tricuspid valve repair (TTVr) with the PASCAL Transcatheter Valve Repair System.BackgroundTTVr has rapidly developed and demonstrated favorable acute outcomes, but longer follow‐up data are needed.MethodsOverall, 30 patients (age 77 ± 6 years; 57% female) received PASCAL implantation from September 2017 to May 2019 and completed a clinical follow‐up at 12 months.ResultsThe TR etiology was functional in 25 patients (83%), degenerative in three (10%), and mixed in two (7%). All patients had TR severe or greater (massive or torrential in 80%) and heart failure symptoms (90% in NYHA III or IV) under optimal medical treatment. Single‐leaflet device attachment occurred in two patients. Moderate or less TR was achieved in 23/28 patients (82%) at 30 days, which was sustained at 12 months (86%). Two patients underwent repeat TTVr due to residual torrential TR (day 173) and recurrence of severe TR (day 280), respectively.One‐year survival rate was 93%; 6 patients required rehospitalization due to acute heart failure. NYHA functional class I or II was achieved in 90% and 6‐minute walk distance improved from 275 ± 122 m at baseline to 347 ± 112 m at 12‐month (+72 ± 82 m, p < .01). There was no stroke, endocarditis, or device embolization during the follow‐up.ConclusionsTwelve‐month outcomes from this multicenter compassionate use experience with the PASCAL System demonstrated high procedural success, acceptable safety, and significant clinical improvement.
Thermodynamics Determine the Diastereochemical Outcome of Catalytic Reactions
Authors: Marsden Stefan R. , Mestrom Luuk , Wijma Hein J. , Noordam Sander J. , McMillan Duncan G. G. , Hanefeld Ulf 
Published: March 2021

AbstractDiastereomers are characterised by an intrinsic energy difference, and thermodynamics dictate their distribution within a dynamic equilibrium. The characteristic mechanistic reversibility and non‐ideal stereoselectivity of catalysts therefore simultaneously promote both synthesis and epimerization of products during the formation of diastereomers. This feature can even result in the thermodynamic inversion of a chiral centre against the catalyst's stereoselectivity. Here, we provide a comprehensive experimental and theoretical study of factors that govern thermodynamic epimerization in catalysis, using enzymes as example. Our analysis highlights, that the deduction of a catalyst's stereoselectivity based on the absolute configuration of the isolated product constitutes a potential pitfall. The selective formation of either the thermodynamic‐, or the kinetic product is less determined by the catalyst, but rather by the reaction conditions. Next to low temperatures, a high maximal extent of conversion was identified to promote kinetically controlled conditions. For bimolecular reactions, conversions can be conveniently modulated via the use of one substrate in excess. Quantum mechanical calculations accurately predicted the diastereomeric excess under equilibrium conditions, which opens the prospect of a rational choice between thermodynamic and kinetic reaction control at an early stage of process design. Our findings are of critical importance for multi‐step syntheses of stereocomplex molecules via catalytic cascade reactions or artificial metabolic pathways, as the final stereochemistry may be determined by the absolute configuration of the product that is overall lowest in energy.
Transformation of Borrelia burgdorferi
Authors: Seshu J. , Moy Brian E. , Ingle Taylor MacMackin 
Published: March 2021

AbstractTransformation techniques used to genetically manipulate Borrelia burgdorferi, the agent of Lyme disease, play a critical role in generating mutants that facilitate analyses of the role of genes in the pathophysiology of this bacterium. A number of borrelial mutants have been successfully isolated and characterized since the first electrotransformation procedure was established 25 years ago (Samuels, 1995). This article is directed at additional considerations for transforming infectious B. burgdorferi to generate strains retaining the plasmid profile of the parental strain, enabling analysis of transformants for in vitro and in vivo phenotypes. These methods are built on previously published protocols and are intended to add steps and tips to enhance transformation efficiency and recovery of strains amenable for studies involving colonization, survival, and transmission of B. burgdorferi during the vector and vertebrate phases of infection. © 2021 Wiley Periodicals LLC.This article was corrected on 20 July 2022. See the end of the full text for details.Basic Protocol 1: Preparation of stock cultures, propagation of spirochetes, and analysis of plasmid profilesBasic Protocol 2: Preparation of plasmid and linear DNA templates for transformationBasic Protocol 3: Transformation of B. burgdorferiBasic Protocol 4: Antibiotic selection of borrelial transformantsBasic Protocol 5: Isolation of borrelial transformants in agar overlaysBasic Protocol 6: Complementation of mutant borrelial strains in cis or in trans
RAG deficiencies: Recent advances in disease pathogenesis and novel therapeutic approaches
Authors: Bosticardo Marita , Pala Francesca , Notarangelo Luigi D. 
Published: March 2021

AbstractThe RAG1 and RAG2 proteins initiate the process of V(D)J recombination and therefore play an essential role in adaptive immunity. While null mutations in the RAG genes cause severe combined immune deficiency with lack of T and B cells (T−B− SCID) and susceptibility to life‐threatening, early‐onset infections, studies in humans and mice have demonstrated that hypomorphic RAG mutations are associated with defects of central and peripheral tolerance resulting in immune dysregulation. In this review, we provide an overview of the extended spectrum of RAG deficiencies and their associated clinical and immunological phenotypes in humans. We discuss recent advances in the mechanisms that control RAG expression and function, the effects of perturbed RAG activity on lymphoid development and immune homeostasis, and propose novel approaches to correct this group of disorders.
PD‐1‐specific “Blocking” antibodies that deplete PD‐1+ T cells present an inconvenient variable in preclinical immunotherapy experiments
Authors: Polesso Fanny , Munks Michael W. , Rott Katherine H. , Smart Savannah , Hill Ann B. , Moran Amy E. 
Published: March 2021

AbstractTherapeutic antibodies blocking PD‐1‐/PD‐L1 interaction have achieved remarkable clinical success in cancer. In addition to blocking a target molecule, some isotypes of antibodies can activate complement, NK cells or phagocytes, resulting in death of the cell expressing the antibody's target. Human anti‐PD‐1 therapeutics use antibody isotypes designed to minimize such antibody‐dependent lysis. In contrast, anti‐PD‐1 reagents used in mice are derived from multiple species, with different isotypes, and are not engineered to reduce target cell death: few studies analyze or discuss how antibody species and isotype may impact data interpretation. We demonstrate here that anti‐PD‐1 therapy to promote activation and proliferation of murine PD‐1‐expressing CD8 T cells sometimes led instead to a loss of antigen specific cells. This phenomenon was seen in two tumor models and a model of virus infection, and varied with the clone of anti‐PD‐1 antibody. Additionally, we compared competition among anti‐PD‐1 clones to find a combination that allows detection of PD‐1‐expressing cells despite the presence of blocking anti‐PD1 antibodies in vivo. These data bring attention to the possibility of unintended target cell depletion with some commonly used anti‐mouse PD‐1 clones, and should provide a valuable resource for the design and interpretation of anti‐PD‐1 studies in mice.
Ameliorative effect of betanin on experimental cisplatin‐induced liver injury; the novel impact of miRNA‐34a on the SIRT1/PGC‐1α signaling pathway
Authors: El Shaffei Ismail , Abdel‐Latif Ghada A. , Farag Doaa B. , Schaalan Mona , Salama Rania M. 
Published: March 2021

AbstractThe anticancer agent, cisplatin (CIS), is associated with hepatotoxic effects related to activation of oxidative stress and inflammation pathways. CIS‐induced oxidative DNA damage reduces sirtuin 1 (SIRT1) activity, which in turn, modulates the activity of peroxisome proliferator‐activated receptor‐gamma coactivator 1‐alpha (PGC‐1α). Moreover, microRNA‐34a (miRNA‐34a) was shown to hinder both SIRT1 and nuclear factor erythroid 2‐related factor 2 (Nrf2) activity. Thus, targeting such a pathway can alleviate CIS‐induced hepatotoxicity. Betanin (BET) is a natural red glycoside food dye obtained from beets, which is reported to exhibit antioxidant function. However, its role in CIS‐induced liver injury and the molecular mechanism has not been fully elucidated. Thus, the aim of this study was to investigate the ameliorative effect of BET on CIS‐induced acute hepatotoxicity through the SIRT1/PGC‐1α signaling pathway and illustrate the impact of miRNA‐34a. Seventy‐two rats were divided into six equal groups: (1) Control, (2) BET, (3) CIS, (4) CIS/BET, (5) CIS/EX527, and (6) CIS/BET/EX527. CIS‐induced liver injury was evidenced by deregulated BAX and BCL2 levels, decreased levels of AMP‐activated protein kinase and PGC‐1α expression, and decreased SIRT1 activity. Consequently, reduced levels of Nrf2 and the expression of associated heme oxygenase‐1 and glutamate‐cysteine ligase modifier subunit were observed. Intriguingly, BET succeeded in reducing the CIS‐induced liver injury through reducing miRNA‐34a expression and enhancing the SIRT1/PGC‐1α pathway. These findings coincide with the molecular docking results and the histopathological picture. In conclusion, the current research provided novel findings of the BET ameliorative effect on CIS‐induced liver injury through modulating miRNA‐34a expression and the SIRT1/PGC‐1α signaling cascade.
Effect of olive mill wastewaters on Scenedesmus sp. growth, metabolism and polyphenols removal
Authors: Dahmen‐Ben Moussa Ines , Maalej Amina , Masmoudi Mohamed A , Feki Firas , Choura Sirine , Baccar Nidhal , Jelail Lobna , Karray Fatma , Chamkha Mohamed , Sayadi Sami 
Published: March 2021

AbstractBACKGROUNDThe three‐phase extraction process of olive oil produces highly contaminated wastewater (OMW). The elimination of this toxic by‐product is an important environmental issue that requires the development of an appropriate management solution. The cultivation of microalgae using OMW as growth medium was therefore studied using single (the culture medium was formed by 0% to 80% ultrafiltered olive mill wastewater (OMUF) or OMW added to BG11) and two‐stage strategies (microalgae were firstly cultivated in the BG11 medium. In the second stage, 40% and 80% of OMUF and OMW were added to the culture). In this work, biodegradation of OMW and subsequent extraction of lipid and antioxidant molecules was investigated as an ecofriendly method for the bioremediation and valorization of OMW.RESULTSFor two‐stage cultivation, OMUF and OMW stress enhanced the intracellular amount of polyphenol accumulated in Scenedesmus sp. and exhibited the highest 2, 2‐diphenyl−1‐ picrylhydrazyl radical (DPPH) and 2,2'‐azino‐bis (3‐ethylbenzoline‐6‐sulfonate) radical (ABTS) scavenging ability compared with single‐stage cultivation. Moreover, the lipid profile is dominated by polyunsaturated acids. In the single‐stage cultivation, the Ch a, Ch b, carotenoid, carbohydrate and lipid content of 2.57, 7.4, 1.69, 368, and 644 g kg−1 were observed in 40% OMUF added culture, respectively, along with high biomass productivity and 58% of polyphenol removal. Moreover, the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay showed that the biomass of Scenedesmus sp. cultured on 40% OMUF did not show any toxic effect, making it an efficient strategy.CONCLUSIONThe results indicate that Scenedesmus sp. is a promising microalga for the biotreatment of OMW and the extraction of bioactive metabolites. © 2021 Society of Chemical Industry.
Use of ohmic heating as an alternative method for cooking pasta
Authors: Turgut Yelizcan , Turgut Sebahattin Serhat , Karacabey Erkan 
Published: March 2021

AbstractBACKGROUNDIn this study, the alternative method of ohmic heating (OH) was applied to investigate its potential usage in the cooking process for pasta and its comparison with the conventional method. For this purpose, OH was operated at four different voltage gradients (10, 20, 30, 40 V cm−1). The electrical conductivity of pasta σ (S m−1) was calculated for the temperature range 22–95 °C and a three‐phase linear relation between σ and temperature was determined.RESULTSAccording to the results, the energy consumption of the OH system and cooking time were lower than the conventional method. Energy conservation was about 73.7% at 40 V cm−1 and increased up to 90.4% (at 10 V cm−1) with lower voltage gradients. Total cooking time, cooking loss, water absorption, degree of gelatinization, volume uptake, energy consumption and sensorial properties were investigated. No significant differences between the results of samples cooked with the conventional method and OH at 30–40 V cm−1 were found in terms of starch gelatinization degree, volume change, water absorption, and sensorial analysis (P > 0.05).CONCLUSIONThese results revealed that OH did not cause any negative effects on the quality parameters of pasta samples, and positive effects were observed on energy and time saving. © 2021 Society of Chemical Industry.
Development of machine learning model algorithm for prediction of 5‐year soft tissue myxoid liposarcoma survival
Authors: Kamalapathy Pramod N. , Ramkumar Dipak B. , Karhade Aditya V. , Kelly Sean , Raskin Kevin , Schwab Joseph , Lozano‐Calderón Santiago 
Published: March 2021

AbstractBackgroundPredicting survival in myxoid liposarcoma (MLS) patients is very challenging given its propensity to metastasize and the controversial role of adjuvant therapy. The purpose of this study was to develop a machine‐learning algorithm for the prediction of survival at five years for patients with MLS and externally validate it using our institutional cohort.MethodsTwo databases, the surveillance, epidemiology, and end results program (SEER) database and an institutional database, were used in this study. Five machine learning models were created based on the SEER database and performance was rated using the TRIPOD criteria. The model that performed best on the SEER data was again tested on our institutional database.ResultsThe net‐elastic penalized logistic regression model was the best according to our performance indicators. This model had an area under the curve (AUC) of 0.85 when compared to the SEER testing data and an AUC of 0.76 when tested against institutional database. An application to use this calculator is available at https://sorg-apps.shinyapps.io/myxoid_liposarcoma/.ConclusionMLS is a soft‐tissue sarcoma with adjunct treatment options that are, in part, decided by prognostic survival. We developed the first machine‐learning predictive algorithm specifically for MLS using the SEER registry that retained performance during external validation with institutional data.
Influence of residents' perceptions of tourism development on their affective commitment, altruistic behavior, and civic virtue for community
Authors: Tang Ruohan , Kang Sung‐Eun , Lee Won Seok , Park Sunwoo 
Published: March 2021

AbstractUsing indigenous minorities in Xijian Miao Village in China as a case research, this research examined how residents' perceptions of tourism development could influence their affective commitment, altruistic behavior, and civic virtue. A total of 449 residents took part in the survey. Using structural equation modeling (SEM), this study found that affective commitment was significantly influenced by perceptions of tourism development. It also found that altruistic behavior and civic virtue had a positive relationship with residents' affective commitment.
Short‐term Oral Steroids Significantly Improves Chronic Rhinosinusitis Without Nasal Polyps
Authors: De Silva April P. , Schembri Mark A. , Sarah Angus H. , Chao Jessica , Yip Kwok Ho , Cildir Gökhan , Lopez Angel , Tumes Damon J. , Pant Harshita 
Published: March 2021

Objectives/HypothesisThe efficacy of short‐term oral corticosteroids in chronic rhinosinusitis without nasal polyps (CRSsNP) is unknown. The aim of this controlled study was to assess the immediate and long‐term outcomes from a short course of a commonly used oral corticosteroid, prednisolone, in well‐defined CRSsNP patients.Study DesignProspective, observational controlled study.MethodsA prospective‐controlled study of CRSsNP patients treated with prednisolone at 0.5 mg/kg tapered over 10 days and non‐prednisolone treated CRSsNP patients (controls) and follow‐up at 2, 6, and 12 months. Baseline and follow‐up SinoNasal Outcome Test (SNOT)‐22, nasal endoscopy (Lund‐Kennedy), and sinus CT scan scores (Lund‐Mackay) were compared.ResultsAt 2 months, there was a significant improvement in the SNOT‐22, nasal endoscopy, and sinus CT scan scores in the prednisolone group (P < .0001) compared with controls (p = ns, Mann–Whitney U test). 52.5% of prednisolone‐treated CRSsNP patients had improved symptoms and did not require sinus surgery at 12 months compared with 14.3% of controls (P < .001). Side‐effects were reported in 8.9% of prednisolone‐treated patients. Patients who benefited from prednisolone had a median symptom duration of 7.25 (99% confidence, upper limit of 11) months compared with 18 months in those requiring surgery.ConclusionsShort‐term oral prednisolone significantly improved all three clinical measures of disease in CRSsNP patients and avoided surgical intervention in 52.5% patients in the first 12 months. Patients with symptoms for less than 11 months were most likely to benefit. The side‐effects of oral steroids require careful consideration and further studies are needed to ascertain appropriate dosage and treatment duration.Level of Evidence3 Laryngoscope, 131:E2618–E2626, 2021
Recent Advances of Polymer‐Based Pure Organic Room Temperature Phosphorescent Materials
Authors: Wang Jun , Lou Xin‐Yue , Wang Yan , Tang Jun , Yang Ying‐Wei 
Published: March 2021

AbstractRoom temperature phosphorescence (RTP) has attracted broad attention due to their long lifetimes, large Stokes shift, and widespread applications. Achieving RTP emission has long been a challenging task under common conditions, for the necessary requirements of promoting intersystem crossing processes and suppressing nonradiative transitions are always tough to meet. Over the past decade, RTP has been obtained through several specific strategies, among which an important method lies in immobilizing phosphors into polymer matrices. Via the effect of steric overcrowding exerted by the polymeric structures, the phosphorescence of the initial phosphors can be promoted significantly. Hence, polymer‐based pure organic materials have proved to be one newly emerging subject in the field of RTP materials. In this review article, the progresses of polymer‐based pure organic room temperature phosphorescent materials are elaborated from four main approaches, including doped polymer systems, copolymer systems, homopolymer systems, and host–guest complexation systems, whereby the design principles, synthesis methods, possible mechanisms, and applications are summarized and discussed in detail.
Elevation of fast but not slow troponin I in the circulation of patients with Becker and Duchenne muscular dystrophy
Authors: Barthel Benjamin L. , Cox Dan , Barbieri Marissa , Ziemba Michael , Straub Volker , Hoffman Eric P. , Russell Alan J. 
Published: March 2021

AbstractIntroductionOne of the hallmarks of injured skeletal muscle is the appearance of elevated skeletal muscle proteins in circulation. Human skeletal muscle generally consists of a mosaic of slow (type I) and fast (type IIa, IIx/d) fibers, defined by their myosin isoform expression. Recently, measurement of circulating fiber‐type specific isoforms of troponin I has been used as a biomarker to suggest that muscle injury in healthy volunteers (HV) results in the appearance of muscle proteins from fast but not slow fibers. We sought to understand if this is also the case in severe myopathy patients with Becker and Duchenne muscular dystrophy (BMD, DMD).MethodsAn enzyme‐linked immunosorbent assay (ELISA) that selectively measures fast and slow skeletal troponin I (TNNI2 and TNNI1) was used to measure a cross‐section of patient plasma samples from HV (N = 50), BMD (N = 49), and DMD (N = 132) patients. Creatine kinase (CK) activity was also measured from the same samples for comparison.ResultsTNNI2 was elevated in BMD and DMD and correlated with the injury biomarker, CK. In contrast, TNNI1 levels were indistinguishable from levels in HV. There was an inverse relationship between CK and TNNI2 levels and age, but no relationship for TNNI1.DiscussionWe define a surprising discrepancy between TNNI1 and TNNI2 in patient plasma that may have implications for the interpretation of elevated muscle protein levels in dystrophinopathies.