bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative study of PF‐06438179/GP1111 (an infliximab biosimilar) and reference infliximab in patients with moderate to severe active rheumatoid arthritis: A subgroup analysis
Authors: Kameda Hideto , Uechi Eishi , Atsumi Tatsuya , Abud‐Mendoza Carlos , Kamei Kazumasa , Matsumoto Tsugumi , Ponce de Leon Dario , Rehman Muhammad I. , Zhang Min , Radominski Sebastiao C. 
Published: June 2020

AbstractAimPF‐06438179/GP1111 (PF‐SZ‐IFX) is a biosimilar of reference infliximab (Remicade®). This analysis compared the efficacy of PF‐SZ‐IFX and reference infliximab sourced from the European Union (IFX‐EU) in patient subgroups from a randomized, comparative study of PF‐SZ‐IFX versus IFX‐EU.MethodsPatients with rheumatoid arthritis were randomized 1:1 to PF‐SZ‐IFX (n = 324) or IFX‐EU (n = 326); study drug (3 mg/kg) was administered intravenously at weeks 0, 2, and 6, then every 8 weeks thereafter. Subgroup analyses of efficacy endpoints such as American College of Rheumatology criteria for ≥20% clinical improvement (ACR20), change in high‐sensitivity C‐reactive protein (hs‐CRP), and change in Disease Activity Score in 28 joints, four components based on hs‐CRP (DAS28‐CRP) at weeks 14 and 30 were performed by age, gender, race, region, immunogenicity status, and treatment history.ResultsOverall, ACR20 response rates as well as changes in DAS28‐CRP and hs‐CRP at week 14 were similar between PF‐SZ‐IFX and IFX‐EU within the subgroups of age, gender, race, region, treatment history, and immunogenicity status. Results to week 30 support overall similarity in efficacy between the two treatment arms in all subgroups.ConclusionOverall, PF‐SZ‐IFX and IFX‐EU were similar in efficacy within the analyzed subgroups of age, gender, race, region, treatment history, and immunogenicity status. The efficacy results from these subgroup analyses were aligned with the previously described results for the overall population up to week 30.
Tofacitinib in the treatment of Indian patients with rheumatoid arthritis: A post hoc analysis of efficacy and safety in Phase 3 and long‐term extension studies over 7 years
Authors: Chopra Arvind , Shobha Vineeta , Chandrashekara Srikantiah , Veeravalli Sarath C. M. , Sharma Reena , Rao Uppuluri R. , Pandya Sapan , Wagh Shrikant , Kadel Jugal K. , Thorat Amit V. , Adhav Charles , Santos Estrella Paul , Yu Wei , Kwok Kenneth , Wouters Ann 
Published: June 2020

AbstractObjectivesTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized tofacitinib efficacy/safety in Indian vs rest of the world (ROW; excluding India) RA patients.MethodsEfficacy data were pooled for disease‐modified antirheumatic drug (DMARD) inadequate responders from Phase (P)3 studies. For Indian patients, ORAL Solo and ORAL Scan; ROW (excluding India), these studies plus ORAL Step, ORAL Sync, and ORAL Standard. Safety data also included ORAL Start (P3; methotrexate‐naïve) and ORAL Sequel (long‐term extension [LTE] study; data cut‐off March 2017) for Indian patients, and these studies plus A3921041 (LTE study; Japanese study) for ROW. Efficacy outcomes at months 3/6: American College of Rheumatology (ACR)20/50/70; Disease Activity Score in 28 joints, erythrocyte sedimentation rate remission/low disease activity; change from baseline in Health Assessment Questionnaire‐Disability Index. Incidence rates (IRs; patients with events/100 patient‐years) for adverse events of special interest (AESIs) were assessed throughout. Descriptive data underwent no formal comparison.ResultsOne‐hundred‐and‐ninety‐seven Indian and 3879 ROW patients were included. Compared with ROW patients, Indian patients were younger, had lower body mass index, shorter RA duration, and higher baseline disease activity; most Indian patients were non‐smokers and all were biologic DMARD (bDMARD)‐naïve. Month 3 ACR20 rates with tofacitinib 5 mg twice daily/10 mg twice daily/placebo were 67.4%/82.1%/40.9% (India) and 59.0%/66.1%/28.2% (ROW), and month 6 rates were 76.2%/92.1%/88.9% (India) and 69.0%/74.2%/66.5% (ROW). Month 3/6 improvements in other outcomes were generally numerically greater with tofacitinib vs placebo, and similar in both populations. Compared with ROW, Indian patients had numerically fewer AEs/serious AEs, and similar IRs for discontinuations due to AEs and AESIs, except that tuberculosis (TB) IR was higher in Indian (IR = 1.21; 95% CI 0.49, 2.49) vs ROW patients (IR = 0.17; 95% CI 0.11, 0.25).ConclusionsTofacitinib efficacy/safety were similar in both populations, except TB IR, which was higher in Indian patients but in line with those in bDMARD‐treated RA patients from high‐risk countries (IR = 0.00‐2.56; TB IR >0.05 [World Health Organization]). Limitations included the small Indian population and baseline differences between populations.
Prevention and treatment of suspected pneumonia in Ethiopian children less than five years from household to primary care
Authors: Tariku Amare , Okwaraji Yemisrach B. , Worku Alemayehu , Biks Gashaw Andargie , Åke Persson Lars , Berhane Yemane 
Published: June 2020

AbstractAimEthiopia has implemented the integrated community case management to reduce mortality in childhood diseases. We analysed prevention, care seeking and treatment of suspected pneumonia from household to health facility in Ethiopia.MethodsAnalyses were based on a survey in four regions that included modules covering 5714 households, 169 health posts with 276 health extension workers and 155 health centres with 175 staff. Caregivers of children aged 2‐59 months responded to questions on awareness of services and care seeking for suspected pneumonia. Pneumonia‐related knowledge of health workers was assessed.ResultsWhen a child had suspected pneumonia, 46% (95% CI: 25,68) sought care at health facilities, and 27% (95% CI: 12,51) received antibiotics. Forty‐one per cent had received full immunisation. One‐fifth (21%, 95%: 19,22) of the caregivers were aware of pneumonia treatment. Sixty‐four per cent of the health extension workers correctly mentioned fast or difficult breathing as signs of suspected pneumonia, and 88% suggested antibiotics treatment.ConclusionThe caregivers' awareness of suspected pneumonia treatment and the utilisation of these services were low. Some of the health extension workers were not knowledgeable about suspected pneumonia. Strengthening primary health care, including immunisation, and enhancing the utilisation of services are critical for further reduction of pneumonia mortality.
Activated FMS‐like tyrosine kinase 3 ameliorates angiotensin II‐induced cardiac remodelling
Authors: Ma Wenzhuo , Liang Fanfan , Zhan Heqin , Jiang Xixi , Gao Chenying , Zhang Xin , Zhang Kaina , Sun Qiang , Hu Hao , Zhao Zhenghang 
Published: June 2020

AbstractAimFMS‐like receptor tyrosine kinase 3 (Flt3) has been reported to be increased in cardiomyocytes responding to ischaemic stress. This study was to determine whether Flt3 activation could ameliorate pressure overload‐induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action.MethodsIn vivo cardiac hypertrophy and remodelling experiments were conducted by infusing angiotensin II (Ang II) chronically in male C57BL/6 mice. Flt3‐specific ligand (FL) was administered intraperitoneally every two days (5 µg/mouse). In vitro experiments on hypertrophy, apoptosis and autophagy mechanism were performed in neonatal rat cardiomyocytes (NRCMs) and H9c2 cells with adenovirus vector‐mediated overexpression of Flt3.ResultsOur results demonstrated that following chronic Ang II infusion for 4 weeks, the mice exhibited heart hypertrophy, fibrosis, apoptosis and contractile dysfunction. Meanwhile, Ang II induced autophagic responses in mouse hearts, as evidenced by increased LC3 II and decreased P62 expression. These pathological alterations in Ang II‐treated mice were significantly ameliorated by Flt3 activation with FL administration. In NRCMs and Flt3‐overexpressed H9c2 cells, FL attenuated Ang II‐induced pathological autophagy and inactivated AMPK/mTORC1/FoxO3a signalling, thereby efficiently mitigating cell hypertrophy and apoptosis. Conversely, the AMPK activator metformin or the mTORC1 inhibitor rapamycin reversed the effects of FL on the alterations of autophagy, hypertrophy and apoptosis in cardiomyocytes induced by Ang II.ConclusionFlt3 activation ameliorates cardiac hypertrophy, fibrosis and contractile dysfunction in the mouse model of chronic pressure overload, most likely via suppressing AMPK/mTORC1/FoxO3a‐mediated autophagy. These results provide new evidence supporting Flt3 as a novel therapeutic target in maladaptive cardiac remodelling.
Reducing dropout in acceptance and commitment therapy, mindfulness‐based cognitive therapy, and problem‐solving therapy for chronic pain and cancer patients using motivational interviewing
Authors: Malins Sam , Biswas Sanchia , Rathbone James , Vogt William , Pye Naomi , Levene Jo , Moghaddam Nima , Russell John 
Published: June 2020

ObjectiveAcceptance and commitment therapy, mindfulness‐based cognitive therapy, and problem‐solving therapy are types of cognitive‐behavioural therapy (CBT) group that improve physical and mental health in chronic pain or cancer. However, dropout is high due to group demands alongside physical impairments. Motivational interviewing (MI) is a well‐evidenced means of enhancing treatment adherence. Few studies have investigated MI as an adjunct to CBT in cancer or chronic pain, and none have established the minimum MI duration required for adherence improvement. This study evaluated minimal‐duration MI to improve adherence in three CBT group types for cancer and chronic pain.MethodsIn a cohort study of 99 cancer and chronic pain patients, 47 were given a 10‐ to 15‐min structured MI telephone intervention (MI‐call) after the first session. The remaining 52 received a CBT group without MI (no‐MI).ResultsOdds of completing group CBTs were five times greater for patients in the MI‐call cohort versus no‐MI. Effects remained when controlling for age, gender, diagnosis, group type, and baseline quality of life. The MI‐call cohort attended one extra session per patient compared to no‐MI, controlling for age, gender, and diagnosis.ConclusionsA brief MI telephone intervention may improve adherence to group CBTs in cancer and chronic pain.Practitioner points

A brief motivational interviewing (MI) telephone intervention may reduce dropout from group cognitive‐behavioural therapies (CBTs) for cancer and chronic pain patients when administered after the first group session in routine care.

Recipients of this intervention were five times more likely to complete a group CBT programme than those who did not receive it.

Therefore, a minimal‐dose MI intervention can have clinically important effects on dropout in group CBTs for patients with long‐term conditions.

It is unclear whether this intervention would also result in greater outcome improvements.
Platelet hyperactivation in multiple myeloma is also evident in patients with premalignant monoclonal gammopathy of undetermined significance
Authors: O’Sullivan Leanne R. , Meade‐Murphy Gerardene , Gilligan Oonagh M. , Mykytiv Vitaliy , Young Paul W. , Cahill Mary R. 
Published: June 2020

SummaryThrombotic events are common in patients with multiple myeloma (MM), smouldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS). Previous studies have indicated platelet hyperactivation as a feature of thrombotic risk in MM, but there is a dearth of data in MGUS. In the present study, multiparameter analysis of platelet activation and responsiveness was investigated by flow cytometry in patients with MGUS, SM/MM and healthy controls (HCs). The median platelet surface CD63 levels, annexin V and PAC‐1 antibody (specific for activated integrin αIIbβ3) binding were significantly elevated in patients with MGUS versus the HCs. These markers were also elevated in SM/MM, but not significantly. In all, 74% of MGUS and 38% of SM/MM patients had one or more elevated marker of platelet activation, compared to 19% of the HCs. Marker‐specific hyporesponsiveness of platelets to agonist [adenosine diphosphate (ADP), thrombin receptor‐activating peptide 6] stimulation in vitro was observed, with significantly reduced surface levels of P‐selectin in response to ADP in patients with MGUS. Platelet‐leucocyte aggregates were not altered in patients, while platelet‐associated immunoglobulins were elevated in a subset of patients. Overall, we found that platelet hyperactivation is prevalent in both MGUS and SM/MM patients and is potentially related to hyporesponsiveness. These observations suggest that further investigation of the predictive and prognostic value of platelet hyperactivation in such patients is warranted.
Challenges in the management of patients with systemic light chain (AL) amyloidosis during the COVID‐19 pandemic
Authors: Kastritis Efstathios , Wechalekar Ashutosh , Schönland Stefan , Sanchorawala Vaishali , Merlini Giampaolo , Palladini Giovanni , Minnema Monique , Roussel Murielle , Jaccard Arnaud , Hegenbart Ute , Kumar Shaji , Cibeira Maria T. , Blade Joan , Dimopoulos Meletios A. 
Published: June 2020

SummaryThe severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐associated coronavirus disease 2019 (COVID‐19) is primarily manifested as a respiratory tract infection, but may affect and cause complications in multiple organ systems (cardiovascular, gastrointestinal, kidneys, haematopoietic and immune systems), while no proven specific therapy exists. The challenges associated with COVID‐19 are even greater for patients with light chain (AL) amyloidosis, a rare multisystemic disease affecting the heart, kidneys, liver, gastrointestinal and nervous system. Patients with AL amyloidosis may need to receive chemotherapy, which probably increases infection risk. Management of COVID‐19 may be particularly challenging in patients with AL amyloidosis, who often present with cardiac dysfunction, nephrotic syndrome, neuropathy, low blood pressure and gastrointestinal symptoms. In addition, patients with AL amyloidosis may be more susceptible to toxicities of drugs used to manage COVID‐19. Access to health care may be difficult or limited, diagnosis of AL amyloidosis may be delayed with detrimental consequences and treatment administration may need modification. Both patients and treating physicians need to adapt in a new reality.
A reconsideration of the radiocarbon dating of the Marine Isotope Stage 3 fauna from southern Ireland
Authors: Carden Ruth F. , Higham Thomas F. G. , Woodman Peter C. 
Published: June 2020

With the improvements in the techniques of radiocarbon dating since the 1990s and the pretreatment of bone samples, it has become apparent that some of the radiocarbon dates from Irish caves such as Castlepook Cave may not be as accurate as previously determined. The faunal remains and sediments within Castlepook Cave are important as this cave is one of only two caves in Ireland in which both pre‐ and post‐Last Glacial Maximum sediments containing faunal remains are found. In this study, samples of identified bones were re‐dated from this cave as well as two others (Foley and Shandon caves) from the same region in the south‐southeast of Ireland. The new dates from Castlepook Cave disclosed results that were significantly older by between c. 5000 and 12 000 radiocarbon years. This was not as apparent in dates obtained from Foley and Shandon caves, where the new dates were older by c. 4000 radiocarbon years on average. The results imply a much older presence of certain mammals during MIS 3 in Ireland and suggest that certain species, notably giant deer and spotted hyaena, may have become locally extirpated before the Last Glacial Maximum, around 40 cal. ka BP.
Digital era open government and democratic governance: The case of Government of Canada Wikipedia editing
Authors: Clarke Amanda , Dubois Elizabeth 
Published: June 2020

AbstractAs digital era open government initiatives are deployed globally, researchers are debating their effects on democratic governance. We develop a framework to evaluate whether these initiatives improve or undermine democratic governance and apply it to the case of Government of Canada Wikipedia editing and an automated Twitter account (@gccaedits) tracking this activity. Through content analysis of edits and analysis of access to information requests we show that while most edits made are useful and non‐partisan, the response of news media and government managers ultimately renders the editing a threat to democratic governance. This complexity highlights the importance of assessing the merits of open government initiatives in their broader socio‐political context. The findings also suggest that more fundamental shifts in contemporary political, media and administrative cultures are necessary before the potential benefits of open government reforms can materialize.
Hypomethylation of Notch1 DNA is associated with the occurrence of uveitis
Authors: Wei H , Yin X , Tang H , Gao Y , Liu B , Wu Q , Tian Q , Hao Y , Bi H , Guo D 
Published: June 2020

SummaryUveitis is a serious intra-ocular inflammatory disease that can lead to visual impairment even blindness worldwide. Notch signaling can regulate the differentiation of naive CD4+ T cells, influencing the development of uveitis. DNA methylation is closely related to the autoimmune diseases. In this study, we measured the Notch1 DNA methylation level, determined the Notch1 and related DNA methylases mRNA expression and evaluated the ratio of T helper type 17 regulatory T cell (Th17/Treg) in peripheral blood mononuclear cells (PBMCs) from uveitis patients and normal control subjects; we also tested the levels of relevant inflammatory cytokines in serum from the participants. Results indicated that compared with those in normal control individuals, the expression of ten–eleven translocation 2 (TET2) and Notch1 mRNA is elevated in uveitis patients, whereas the methylation level in Notch1 DNA promotor region [−842 ~ −646 base pairs (bp)] is down-regulated, and is unrelated to anatomical location. Moreover, the Th17/Treg ratio is up-regulated in PBMCs from uveitis patients, accompanied by the elevated levels of proinflammatory cytokines [e.g. interleukin (IL)-2, IL-6, IL-17 and interferon (IFN)-γ] in serum from uveitis patients. These findings suggest that the over-expression of TET2 DNA demethylase may lead to hypomethylation of Notch1, activate the Notch1 signaling, induce naive CD4+ T cells to differentiate the Th17 subset and thus disturb the balance of the Th17/Treg ratio in uveitis patients. Overall, hypomethylation of Notch1 DNA is closely associated with the occurrence of uveitis. Our study preliminarily reveals the underlying mechanism for the occurrence of uveitis related to the hypomethylation of Notch1 DNA, providing a novel therapeutic strategy against uveitis in clinical practice.
Image Morphing With Perceptual Constraints and STN Alignment
Authors: Fish N. , Zhang R. , Perry L. , Cohen‐Or D. , Shechtman E. , Barnes C. 
Published: June 2020

AbstractIn image morphing, a sequence of plausible frames are synthesized and composited together to form a smooth transformation between given instances. Intermediates must remain faithful to the input, stand on their own as members of the set and maintain a well‐paced visual transition from one to the next. In this paper, we propose a conditional generative adversarial network (GAN) morphing framework operating on a pair of input images. The network is trained to synthesize frames corresponding to temporal samples along the transformation, and learns a proper shape prior that enhances the plausibility of intermediate frames. While individual frame plausibility is boosted by the adversarial setup, a special training protocol producing sequences of frames, combined with a perceptual similarity loss, promote smooth transformation over time. Explicit stating of correspondences is replaced with a grid‐based freeform deformation spatial transformer that predicts the geometric warp between the inputs, instituting the smooth geometric effect by bringing the shapes into an initial alignment. We provide comparisons to classic as well as latent space morphing techniques, and demonstrate that, given a set of images for self‐supervision, our network learns to generate visually pleasing morphing effects featuring believable in‐betweens, with robustness to changes in shape and texture, requiring no correspondence annotation.
Rewilding in the face of climate change
Authors: Carroll Carlos , Noss Reed F. 
Published: June 2020

AbstractExpansion of the global protected‐area network has been proposed as a strategy to address threats from accelerating climate change and species extinction. A key step in increasing the effectiveness of such expansion is understanding how novel threats to biodiversity from climate change alter concepts such as rewilding, which have underpinned many proposals for large interconnected reserves. We reviewed potential challenges that climate change poses to rewilding and found that the conservation value of large protected areas persists under climate change. Nevertheless, more attention should be given to protection of microrefugia, macrorefugia, complete environmental gradients, and areas that connect current and future suitable climates and to maintaining ecosystem processes and stabilizing feedbacks via conservation strategies that are resilient to uncertainty regarding climate trends. Because a major element of the threat from climate change stems from its novel geographic patterns, we examined, as an example, the implications for climate‐adaptation planning of latitudinal, longitudinal (continental to maritime), and elevational gradients in climate‐change exposure across the Yellowstone‐to‐Yukon region, the locus of an iconic conservation proposal initially designed to conserve wide‐ranging carnivore species. In addition to a continued emphasis on conserving intact landscapes, restoration of degraded low‐elevation areas within the region is needed to capture sites important for landscape‐level climate resilience. Extreme climate exposure projected for boreal North America suggests the need for ambitious goals for expansion of the protected‐area network there to include refugia created by topography and ecological features, such as peatlands, whose conservation can also reduce emissions from carbon stored in soil. Qualitative understanding of underlying reserve design rules and the geography of climate‐change exposure can strengthen the outcomes of inclusive regional planning processes that identify specific sites for protection.