bluuebunny/crossref_metadata_2025_split huggingface dataset:
How can we relieve gastrointestinal symptoms in people with cystic fibrosis? An international qualitative survey
Authors: Smith Sherie , Rowbotham Nicola , Davies Gwyneth , Gathercole Katie , Collins Sarah J , Elliott Zoe , Herbert Sophie , Allen Lorna , Ng Christabella , Smyth Alan 
Published: September 2020

IntroductionRelieving gastrointestinal (GI) symptoms was identified as a ‘top ten’ priority by our James Lind Alliance Priority Setting Partnership in cystic fibrosis (CF). We conducted an online survey to find out more about the effect of GI symptoms in CF.MethodsWe co-produced an online survey distributed to the CF community via web-based platforms. The survey consisted of open and closed questions designed to help us learn more about the effects of GI symptoms for people with CF (pwCF). We analysed the data using descriptive statistics and thematic analysis. We promoted the survey via social media and web-based platforms which allowed respondents from any country to take part. Our participants came from the CF community, including: adults and children with CF, parents and close family of pwCF and healthcare professionals (HCPs) working with pwCF.ResultsThere were 276 respondents: 90 (33%) pwCF, 79 (29%) family, 107 (39%) HCPs. The most commonly reported symptoms by lay respondents were stomach cramps/pain, bloating and a ‘combination of symptoms’. The top three symptoms that HCPs said were reported to them were reduced appetite, bloating and constipation. Almost all (94% (85/90)) HCPs thought medications helped to relieve GI symptoms but only 58% (82/141) of lay respondents agreed.ConclusionsOur survey has shown that GI symptoms among our participants are prevalent and intrude on daily lives of pwCF. There is a need for well-designed clinical studies to provide better evidence for management of GI symptoms and complications.
FcγRIIB engagement drives agonistic activity of Fc-engineered αOX40 antibody to stimulate human tumor-infiltrating T cells
Authors: Campos Carrascosa Lucia , van Beek Adriaan A , de Ruiter Valeska , Doukas Michail , Wei Jie , Fisher Timothy S , Ching Keith , Yang Wenjing , van Loon Karlijn , Boor Patrick P C , Rakké Yannick S , Noordam Lisanne , Doornebosch Pascal , Grünhagen Dirk , Verhoef Kees , Polak Wojciech G , IJzermans Jan N M , Ni Irene , Yeung Yik Andy , Salek-Ardakani Shahram , Sprengers Dave , Kwekkeboom Jaap 
Published: September 2020

BackgroundOX40 (CD134) is a costimulatory molecule of the tumor necrosis factor receptor superfamily that is currently being investigated as a target for cancer immunotherapy. However, despite promising results in murine tumor models, the clinical efficacy of agonistic αOX40 antibodies in the treatment of patients with cancer has fallen short of the high expectation in earlier-stage trials.MethodsUsing lymphocytes from resected tumor, tumor-free (TF) tissue and peripheral blood mononuclear cells (PBMC) of 96 patients with hepatocellular and colorectal cancers, we determined OX40 expression and the in vitro T-cell agonistic activity of OX40-targeting compounds. RNA-Seq was used to evaluate OX40-mediated transcriptional changes in CD4+ and CD8+ human tumor-infiltrating lymphocytes (TILs).ResultsHere, we show that OX40 was overexpressed on tumor-infiltrating CD4+ T cells compared with blood and TF tissue-derived T cells. In contrast to a clinical candidate αOX40 antibody, treatment with an Fc-engineered αOX40 antibody (αOX40_v12) with selectively enhanced FcγRIIB affinity, stimulated in vitro CD4+ and CD8+ TIL expansion, as well as cytokine and chemokine secretions. The activity of αOX40_v12 was dependent on FcγRIIB engagement and intrinsic CD3/CD28 signals. The transcriptional landscape of CD4+ and CD8+ TILs shifted toward a prosurvival, inflammatory and chemotactic profile on treatment with αOX40_v12.ConclusionsOX40 is overexpressed on CD4+ TILs and thus represents a promising target for immunotherapy. Targeting OX40 with currently used agonistic antibodies may be inefficient due to lack of OX40 multimerization. Thus, Fc engineering is a powerful tool in enhancing the agonistic activity of αOX40 antibody and may shape the future design of antibody-mediated αOX40 immunotherapy.
Impact of off-hour endovascular therapy on outcomes for acute ischemic stroke: insights from STAR
Authors: Tschoe Christine , Kittel Carol , Brown Patrick , Hafeez Muhammad , Kan Peter , Alawieh Ali , Spiotta Alejandro M , Almallouhi Eyad , Dumont Travis M , McCarthy David J , Starke Robert M , De Leacy Reade , Wolfe Stacey Q , Fargen Kyle M 
Published: September 2020

BackgroundThe off-hour effect has been observed in the medical care of acute ischemic stroke. However, it remains unclear if time of arrival affects revascularization rates and outcomes after endovascular therapy (EVT) for emergent large vessel occlusion (ELVO). We aimed to investigate the clinical outcomes of EVT between on-hour and off-hour admissions.MethodsPatients who underwent EVT for ELVO from January 2013 to June 2019 from the STAR Registry were included. Patients were grouped based on time of groin puncture: on-hour period (Monday through Friday, 7:00 am–4:59 pm) and off-hour period (overnight 5:00pm–6:59am and the weekends). Primary outcome was final modified Rankin Scale (mRS) at 90 days on mRS-shift analysis.ResultsA total of 1919 patients were included in the study from six centers. The majority of patients (1169, 60.9%) of patients presented during the off-hour period. The mean age was 68.1 years and 50.5% were women. Successful reperfusion, as defined by a Thrombolysis In Cerebral Infarction (TICI) score of ≥2B, was achieved in 88.8% in the on-hour group and 88.0% in the off-hour group. Good clinical outcome (mRS 0–2) was obtained in 34.4% of off-hour patients and 37.7% of on-hour patients. On multivariable ordinal logistic regression analysis, time of presentation was not associated with worsened outcome (OR 1.150; 95% CI 0.96 to 1.37; P=0.122). Age, admission National Institutes of Health Stroke Scale (NIHSS), baseline mRS, and final TICI score were significantly associated with worse outcomes.ConclusionThere is no statistical difference in functional outcome in acute ischemic stroke patients who underwent EVT during on-hours versus off-hours.
Influence of simultaneous pressor and vasodilatory agents on the evolution of infarct growth in experimental acute middle cerebral artery occlusion
Authors: Saadat Niloufar , Christoforidis Gregory A , Jeong Yong Ik , Liu Mira , Dimov Alexey , Roth Steven , Niekrasz Marek , Ansari Sameer A , Carroll Timothy 
Published: September 2020

BackgroundThis study sought to test the hypothesis that simultaneous central blood pressure elevation and potent vasodilation can mitigate pial collateral-dependent infarct growth in acute ischemic stroke.MethodsTwenty mongrel canines (20–30 kg) underwent permanent middle cerebral artery occlusion (MCAO). Eight subjects received continuous infusion of norepinephrine (0.1–1.5200 µg/kg/min; titrated to a median of 34 mmHg above baseline mean arterial pressure) and hydralazine (20 mg) starting 30 min following MCAO. Pial collateral recruitment was scored prior to treatment and used to predict infarct volume based on a previously reported parameterization. Serial diffusion magnetic resonance imaging (MRI) acquisitions tracked infarct volumes over a 4-hour time frame. Infarct volumes and infarct volume growth between treatment and control groups were compared with each other and to predicted values. Fluid-attenuated inversion recovery (FLAIR) MRI, susceptibility weighted imaging (SWI), and necropsy findings were included in the evaluation.ResultsDifferences between treatment and control group varied by pial collateral recruitment based on indicator-variable regression effects analysis with interaction confirmed by regression model fit. Benefit in treatment group was only in subjects with poor collaterals which had 35.7% less infarct volume growth (P=0.0008; ANOVA) relative to controls. Measured infarct growth was significantly lower than predicted by the model (linear regression partial F-test, slope P<0.001, intercept=0.003). There was no evidence for cerebral hemorrhage or posterior reversible encephalopathy syndrome.ConclusionOur results indicate that a combination of norepinephrine and hydralazine administered in the acute phase of ischemic stroke mitigates infarct evolution in subjects with poor but not good collateral recruitment.
Fluoroscopically guided mandibular nerve block: a modified lateral approach
Authors: Mojica Jeffrey Jon , Kudur Vinay , Garza III Rudy , Eckmann Maxim S 
Published: September 2020

Background and objectivesMandibular nerve blocks are indicated for atypical face pain and trigeminal neuralgia. We hypothesized that a modified lateral approach, which entailed a combination of lateral and anterior approach techniques to the mandibular nerve block would lead to similar efficacy and improved safety profile rather than the typical lateral or anterior techniques.MethodsThis alternative approach was derived from anatomical investigation using the Radiology Anatomy Atlas Viewer and reconstructed axial cadaveric slices. We used axial slices at the level of the lateral pterygoid plate, and at the level of the temporomandibular joint to devise a needle path appropriate for this block.ResultsThe modified lateral approach to the mandibular nerve block was verified theoretically through cadaveric reconstructed slices and has been successfully performed in our practice. Precise needle trajectory could avoid both periosteal contact and gross redirection, as well as other procedural complications.ConclusionThe modified lateral approach to a mandibular nerve block avoids the respective risks associated with either the lateral and anterior approach. Facial intervention techniques typically pose increased safety challenges, however through cadaveric anatomic reconstruction, we have developed a safer approach for mandibular nerve blockade.
A new model for dark matter fluid sphere
Authors: Das Shyam , Sarkar Nayan , Mondal Monimala , Rahaman Farook 
Published: September 2020

We develop a new model for a spherically symmetric dark matter fluid sphere containing two regions: (i) Isotropic inner region with constant density and (ii) Anisotropic outer region. We solve the system of field equation by assuming a particular density profile along with a linear equation of state. The obtained solutions are well-behaved and physically acceptable which represent equilibrium and stable matter configuration by satisfying the Tolman–Oppenheimer–Volkoff (TOV) equation and causality condition, condition on adiabatic index, Harrison–Zeldovich–Novikov criterion, respectively. We consider the compact star EXO 1785-248 (Mass [Formula: see text] and radius R[Formula: see text]8.8 km) to analyze our solutions by graphical demonstrations.
Models for mathematical systems
Authors: Morris Alfred H. 
Published: September 2020

A program, written for the IBM 7090, which defines a model for a finite collection of associative algebras for the computer, is described and illustrated. The program contains a structure broad enough in scope to allow one to perform operations on such diverse mathematical concepts as differential equations, infinite series and differential forms in a simple yet comprehensive manner, while also serving in a foundation upon which a variety of higher level symbol manipulation languages can be developed.
The development of the structure of this model is given. In particular, it is assumed that a family of not necessarily commutative algebras defined over a collection of commutative rings is given, where the algebras are algebras of modules generated by recursive sets. A brief discussion is given on how the vectors and scalars of these algebras should be represented, and how their basic algebraic operations (addition and multiplication) can be handled in a systematic manner without regard to the specific underlying scalar rings involved. Functional expressions are treated by developing a procedure for assigning an arbitrary list of operators to an algebra, and then assigning to each operator a list of assumptions that it is to satisfy. The latter is accomplished through the use of what are called "axiom" or "partial evaluation" functions. The resulting structure, which is called ALGEBRA, is shown to serve as a model for a family of associative algebras, where the resulting families of equivalence classes of representations for the vectors are uniquely representable. Various related notions, such as topological and decision considerations, are also briefly discussed.
After having outlined the development of the system ALGEBRA, polynomial, exterior and series algebras are given as examples to illustrate how the model can be used. It is observed that a wide variety of mathematical data can be handled fairly simply, depending only on the formulation of the problem under consideration. The possibility of constructing various higher level symbol manipulation languages that have a mathematical structure, broad enough in scope to allow an analyst to manipulate various problems in a variety of ways, is also discussed. A programming language called FLAP has already been developed, demonstrating that such a language can indeed be studied and formulated in a consistent manner.
Epithelial-to-Mesenchymal Transition is a Cause of Both Intrinsic and Acquired Resistance to KRAS G12C Inhibitor in KRAS G12C–Mutant Non–Small Cell Lung Cancer
Authors: Adachi Yuta , Ito Kentaro , Hayashi Yuko , Kimura Ryo , Tan Tuan Zea , Yamaguchi Rui , Ebi Hiromichi 
Published: September 2020

Abstract

Purpose:
KRAS is among the most commonly mutated oncogene in cancer including non–small cell lung cancer (NSCLC). In early clinical trials, inhibitors targeting G12C-mutant KRAS have achieved responses in some patients with NSCLC. Possible intrinsic and acquired resistance mechanisms to KRAS G12C inhibitors are not fully elucidated and will likely become important to identify.

Experimental Design:
To identify potential resistance mechanisms, we defined the sensitivity of a panel of KRAS G12C–mutant lung cancer cell lines to a KRAS G12C inhibitor, AMG510. Gene set enrichment analyses were performed to identify pathways related to the sensitivity, which was further confirmed biochemically. In addition, we created two cell lines that acquired resistance to AMG510 and the underlying resistance mechanisms were analyzed.

Results:
KRAS expression and activation were associated with sensitivity to KRAS G12C inhibitor. Induction of epithelial-to-mesenchymal transition (EMT) led to both intrinsic and acquired resistance to KRAS G12C inhibition. In these EMT-induced cells, PI3K remained activated in the presence of KRAS G12C inhibitor and was dominantly regulated by the IGFR–IRS1 pathway. We found SHP2 plays a minimal role in the activation of the PI3K pathway in contrast to its critical role in the activation of the MAPK pathway. The combination of KRAS G12C inhibitor, PI3K inhibitor, and SHP2 inhibitor resulted in tumor regressions in mouse models of acquired resistance to AMG510.

Conclusions:
Our findings suggest that EMT is a cause of both intrinsic and acquired resistance by activating the PI3K pathway in the presence of KRAS G12C inhibitor.
Long-Term Outcome in High-Risk Patients With Hypertrophic Cardiomyopathy After Primary Prevention Defibrillator Implants
Authors: Rowin Ethan J. , Burrows Austin , Madias Christopher , Estes N.A. Mark , Link Mark S. , Maron Martin S. , Maron Barry J. 
Published: September 2020

Background:
The implantable cardioverter-defibrillator (ICD) is effective for preventing sudden death in patients with hypertrophic cardiomyopathy. However, data on performance and complications of implanted ICDs over particularly long time periods to inform clinical practice is presently incomplete.

Methods:
The study cohort comprises 217 consecutive hypertrophic cardiomyopathy patients with primary prevention ICDs implanted before 2008 and followed for ≥10 years (mean 12±4; range to 31).

Results:

Patients were 38±17 years at implant and 45 (21%) experienced appropriate interventions terminating ventricular tachycardia/ventricular fibrillation. The majority of ICD discharges occurred ≥5 years after implant (29 patients; 64%), including ≥10 years in 16 patients (36%). Initial device therapy increased in frequency from 2.3% of patients at <1 year to 8.5% of patients at ≥10-years after implant (
P
=0.005). Inappropriate ICD shocks in 39 patients occurred most commonly <5 years after implant (54%) and decreased in frequency with increasing time from implant (from 9.7% of patients at <5 years to 3.8% at ≥10 years,
P
=0.02). Other major device complications including infection and lead fractures and dislodgement occurred in 27 patients (12%) but did not increase in frequency over follow-up after implant (
P
=0.47). There were no arrhythmic sudden death events among the 217 patients with ICD.

Conclusions:
In hypertrophic cardiomyopathy, after a primary prevention implant, ICD therapy often followed prolonged periods of device dormancy and increased progressively in frequency over time, including one-third of patients with initial therapy after 5 to 9 years, and an additional one-third of patients at ≥10 years. Frequency of inappropriate shocks decreased over follow-up, likely reflecting standard changes in device programming, while occurrence of device complications, such as lead fractures/infection, did not increase during follow-up.
Sleep Duration and Stroke
Authors: Titova Olga E. , Michaëlsson Karl , Larsson Susanna C. 
Published: September 2020

Background and Purpose:
Studies of sleep duration in relation to specific types of stroke are scarce. Moreover, the results are inconclusive and causality remains unclear. Our objective was to investigate whether sleep duration is associated with risk of stroke and its types using observational and Mendelian randomization designs.

Methods:
The prospective study included 79 881 women and men (45–79 years of age) who were followed up for incident stroke or death over a mean follow-up of 14.6 years (1 164 646 person-years) through linkage to Swedish Registers. For the Mendelian randomization study, single-nucleotide polymorphisms associated with sleep duration were identified from a genome-wide association study. Summarized data for genetic associations with stroke were obtained from publicly available data of the MEGASTROKE and the International Stroke Genetics Consortia.

Results:
Compared with normal sleep duration, long sleep (≥9 hours per day) was associated with increased risk of total and ischemic stroke (hazard ratios [95% CI], 1.12 [1.03–1.22] and 1.14 [1.03–1.24], respectively), whereas short sleep (<7 h/d) was linked to higher risk of intracerebral hemorrhage (hazard ratio [95% CI], 1.21 [1.03–1.41]). The 2-sample Mendelian randomization analysis supported no causal association of short or long sleep duration with ischemic stroke as a whole.

Conclusions:
In a prospective study, long sleep duration was associated with increased risk of total and ischemic stroke, whereas short sleep was linked to increased risk of intracerebral hemorrhage. However, the Mendelian randomization analysis did not show a significant detrimental effect of short or long sleep duration on the risk of total stroke or stroke types.
Free-Riders in the Nonprofit Industrial Complex: The Problem of Flexitarianism
Authors: Wrenn Corey Lee 
Published: September 2020

Abstract
Social movements have traditionally viewed free-riders as a problem for effective mobilization, but under the influence of the nonprofit industrial complex, it is possible that movements actively facilitate their presence. Free-riders become an economic resource to professionalized movements seeking to increase wealth and visibility in the crowded social movement space by discouraging meaningful attitude or behavior change from their audiences and concentrating power among movement elites. Actively cultivated free-riding is exemplified by the professionalized Nonhuman Animal rights movement which promotes flexitarianism over ethical veganism despite its goal of nonhuman liberation. Major social-psychological theories of persuasion in addition to 44 studies on vegan and vegetarian motivation are examined to illustrate how free-rider flexitarianism is at odds with stated goals, thereby suggesting an alternative utility in flexitarianism as a means of facilitating a disengaged public.
Checklist of the dragonflies and damselflies (Insecta: Odonata) of Bangladesh, Bhutan, India, Nepal, Pakistan and Sri Lanka
Authors: KALKMAN V.J. , BABU R. , BEDJANIČ M. , CONNIFF K. , GYELTSHEN T. , KHAN M.K. , SUBRAMANIAN K.A. , ZIA A. , ORR A.G. 
Published: September 2020

A checklist of the dragonflies and damselflies occurring in Bangladesh, Bhutan, India (including Andaman and Nicobar Islands), Nepal, Pakistan and Sri Lanka is presented. In total 588 (including 559 full species) taxa are known to occur in the region of which 251 taxa (species & subspecies) are single country endemics. Recent taxonomic changes relevant to the area are summarized. Sixteen taxa are synonymized and a checklist of all synonyms established since 1950 is provided. Information is given on available larval descriptions including a list of genera present in the region for which no larvae have yet been described. Numerous species occurring in the area are still poorly known and a list of genera for which a revision is urgently needed is provided. The following new synonyms are established: Calicnemia sudhaae Mitra, 1994 = Calicnemia imitans Lieftinck, 1948 syn. nov.; Ceriagrion fallax cerinomelas Lieftinck, 1927 = Ceriagrion fallax Ris, 1914 syn. nov.; Ceriagrion fallax pendleburyi Laidlaw, 1931 = Ceriagrion fallax Ris, 1914 syn. nov.; Coenagrion kashmirus Chowdhary & Das, 1975 = Ischnura forcipata Morton, 1907 syn. nov.; Enallagma insula Fraser, 1920 = Aciagrion occidentale Laidlaw, 1919 syn. nov.; Himalagrion pithoragarhicum Sahni, 1964 = Ceriagrion fallax Ris, 1914 syn. nov.; Ischnura bhimtalensis Sahni, 1965 = Ischnura rubilio Selys, 1876 syn. nov.; Onychargia indica Sahni, 1964 = Paracercion calamorum (Ris, 1916) syn. nov.; Anaciaeschna kashmirense Singh & Baijal, 1954 = Anaciaeschna martini (Selys, 1897) syn. nov.; Cyclogomphus vesiculosus Selys, 1854 = Cyclogomphus ypsilon Selys, 1954 syn. nov.; Chlorogomphus brittoi Navás, 1934 = Chlorogomphus xanthoptera (Fraser, 1919) syn. nov.; Hylaeothemis indica Fraser, 1946 = Hylaeothemis apicalis Fraser, 1924 syn. nov.; Sympetrum durum Bartenef, 1916 = Sympetrum striolatum commixtum Selys, 1884 syn. nov.; Sympetrum himalayanum Navás, 1934 = Sympetrum hypomelas (Selys, 1884) syn. nov.; Sympetrum haematoneura Fraser, 1924 = Sympetrum speciosum Oguma, 1915 syn. nov.; Sympetrum speciosum taiwanum Asahina, 1951 = Sympetrum speciosum Oguma, 1915 syn. nov. In addition, Periaeschna lebasi Navás, 1930 is regarded a nomen nudum. The following new combinations are proposed: Onychogomphus acinaces Laidlaw, 1922 is transferred to the genus Melligomphus Chao, 1990 resulting in Melligomphus acinaces (Laidlaw, 1922) comb. nov. Onychogomphus saundersii Selys, 1854 is transferred to the genus Nychogomphus Carle, 1986 resulting in Nychogomphus saundersii (Selys, 1854) comb. nov..