bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of bDMARDs on quality of life in patients with psoriatic arthritis: meta-analysis
Authors: Lu Yuqiong , Dai Zhanjing , Lu Yun , Chang Feng 
Published: April 2022

ObjectivesTo determine the effects of biological disease-modifying anti-rheumatic drugs (bDMARDs) on the quality of life (QoL) among patients with psoriatic arthritis (PsA).DesignMeta-analysis.Data sources and eligibility criteriaPubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, WanFang and VIP databases were searched to collect randomised controlled trials (RCTs), which were conducted to evaluate the effect of bDMARDs in the treatment of patients with PsA and reported QoL-related outcomes, from inception to November 2020 and updated on 19 February 2022.Data extraction and synthesisOutcomes about Health Assessment Questionnaire Disability Index (HAQ-DI), Dermatology Life Quality Index, physical component summary and mental component summary of the Short Form 36, EuroQol Visual Analogue Scale, Psoriasis Area Severity Index (PASI) 50/75/90/100 were extracted by two reviewers independently. Data were pooled using the fixed or random effects methods and considered as mean difference (MD) or risk ratio with 95% CI.ResultsOut of 3190 articles screened, 37 RCTs (with 47 articles reported) were included. Pooled estimates showed that bDMARDs were superior versus placebo on all outcomes. Against methotrexate (MTX) and tofacitinib, bDMARDs showed no statistically significant advantages or significant disadvantages. Similar results were found for bDMARDs+MTX versus MTX. For HAQ-DI, the results of the subgroups of bDMARDs versus placebo, bDMARDs+MTX versus MTX, bDMARDs versus tofacitinib and bDMARDs versus MTX were −0.21 (MD, 95% CI, −0.23 to –0.18), −0.22 (MD, 95% CI, −0.58 to 0.14), –0.01 (MD, 95% CI, −0.05 to 0.04) and –0.03 (MD, 95% CI, −0.04 to –0.02), respectively.ConclusionsCompared with placebo, bDMARDs taken by patients with PsA appear to significantly improve the QoL. Compared with other therapeutic agents, more studies are required to confirm the effect of single and combined bDMARDs use further.
Contribution of supervision to the development of advanced practitioners: a qualitative study of pharmacy learners’ and supervisors’ views
Authors: Hindi Ali Mawfek Khaled , Willis Sarah Caroline , Astbury Jayne , Fenton Catherine , Stearns Selma , Jacobs Sally , McDermott Imelda , Moss Aidan , Seston Elizabeth , Schafheutle Ellen Ingrid 
Published: April 2022

ObjectiveTo apply educational theory to explore how supervision can contribute to the development of advanced practitioners using the example of several postregistration primary care training pathways for pharmacy professionals (pharmacists and pharmacy technicians).DesignQualitative semistructured telephone interviews applying Billet’s theory of workplace pedagogy for interpretation.SettingEngland.ParticipantsFifty-one learners and ten supervisors.Primary outcomeContribution of clinical and educational supervision to the development of advanced practitioners in primary care.ResultsFindings were mapped against the components of Billet’s theory to provide insights into the role of supervision in developing advanced practitioners. Key elements for effective supervision included supporting learners to identify their learning needs (educational supervision), guiding learners in everyday work activities (clinical supervision), and combination of regular prearranged face-to-face meetings and ad hoc contact when needed (clinical supervision), along with ongoing support as learners progressed through a learning pathway (educational supervision). Clinical supervisors supported learners in developing proficiency and confidence in translating and applying the knowledge and skills they were gaining into practice. Learners benefited from having clinical supervisors in the workplace with good understanding and experience of working in the setting, as well as receiving clinical supervision from different types of healthcare professionals. Educational supervisors supported learners to identify their learning needs and the requirements of the learning pathway, and then as an ongoing available source of support as they progressed through a pathway. Educational supervisors also filled in some of the gaps where there was a lack of local clinical supervision and in settings like community pharmacy where pharmacist learners did not have access to any clinical supervision.ConclusionsThis study drew out important elements which contributed to effective supervision of pharmacy advanced practitioners. Findings can inform the education and training of advanced practitioners from different professions to support healthcare workforce development in different healthcare settings.
Responsiveness of the HUG-5 in an outpatient clinic: a 12-month randomised feasibility study protocol
Authors: Kennedy Kevin , Nanji Keean , Patil Nikhil , Wu Michael , Xie Jim , Chan Jenny , Hatamnejad Amin , Chan Brian , Xie Feng , Sogbesan Enitan 
Published: April 2022

IntroductionGlaucoma is a progressive, chronic condition that can have a significant impact on a patient’s health-related quality of life (HRQoL). Validated, disease-specific HRQoL tools such as the Health Utility for Glaucoma (HUG-5) tool and the Glaucoma Quality of Life Questionnaire (GlauQoL-17) can be used to monitor a patient’s quality of life. However, the utility of these tools in outpatient clinic practice is not well established. The primary objective of this study is to characterise the feasibility of administering periodic HRQoL questionnaires in glaucoma using a semi-automated workflow.Methods and analysisThis study will be a single-centre, unblinded, randomised, parallel-group study with an exploratory data analysis framework. We aim to determine the feasibility of administering the HUG-5 in an outpatient clinic using a semi-automated workflow and determine patient engagement through email and telephone contact methods. We will also be investigating the association of the HUG-5 and GlauQoL-17 with patient visual field testing and visual acuity. Mean differences between groups will be tested with analysis of variance to determine if the frequency of calls affects burden, satisfaction and perceived value of information.Ethics and disseminationThis study has been approved by the Hamilton Integrated Research Ethics board (ID: 13046) and will be conducted within Canadian Tri-Council Statement policy. Personal information of the study’s participants will be anonymised with identification codes and data will be kept on an encrypted server. Results of this study will be disseminated through peer-reviewed journals, conferences and internal meetings.
Benefit of successful reperfusion achieved by endovascular thrombectomy for patients with ischemic stroke and moderate pre-stroke disability (mRS 3): results from the MR CLEAN Registry
Authors: Benali Faysal , Kappelhof Manon , Ospel Johanna , Ganesh Aravind , McDonough Rosalie V , Postma Alida A , Goldhoorn Robert-Jan Berend , Majoie Charles B L M , van den Wijngaard Ido , Lingsma Hester F , Vos Jan Albert , van Oostenbrugge Robert J , van Zwam Wim H , Goyal Mayank 
Published: April 2022

BackgroundPre-stroke dependent patients (modified Rankin Scale score (mRS) ≥3) were excluded from most trials on endovascular treatment (EVT) for acute ischemic stroke (AIS) in the anterior circulation. Therefore, little evidence exists for EVT in those patients. We aimed to investigate the safety and benefit of EVT in pre-stroke patients with mRS score 3.MethodsWe used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic stroke in the Netherlands (MR CLEAN) Registry. All patients treated with EVT for anterior circulation AIS with pre-stroke mRS 3 were included. We assessed causes for dependence and compared patients with successful reperfusion (defined as expanded Thrombolysis in Cerebral Ischemia scale (eTICI) 2b–3) to patients without successful reperfusion. We used regression analyses with pre-specified adjustments. Our primary outcome was 90-day mRS 0–3 (functional improvement or return to baseline).ResultsA total of 192 patients were included, of whom 82 (43%) had eTICI <2b and 108 (56%) eTICI ≥2b. The median age was 80 years (IQR 73–87). Fifty-one of the 192 patients (27%) suffered from previous stroke and 36/192 (19%) had cardiopulmonary disease. Patients with eTICI ≥2b more often returned to their baseline functional state or improved (n=26 (26%) vs n=15 (19%); adjusted odds ratio (aOR) 2.91 (95% CI 1.08 to 7.82)) and had lower mortality rates (n=49 (49%) vs n=50 (64%); aOR 0.42 (95% CI 0.19 to 0.93)) compared with patients with eTICI <2b.ConclusionsAlthough patients with AIS with pre-stroke mRS 3 comprise a heterogenous group of disability causes, we observed improved outcomes when patients achieved successful reperfusion after EVT.
RETRACTED ARTICLE: Direct measurements of the $$^{12}$$C+$$^{12}$$C reactions cross-sections towards astrophysical energies
Authors: Morales-Gallegos L. , Aliotta M. , Gialanella L. , Best A. , Bruno C. G. , Buompane R. , Davinson T. , De Cesare M. , Di Leva A. , D’Onofrio A. , Duarte J. G. , Gasques L. R. , Imbriani G. , Porzio G. , Rapagnani D. , Romoli M. , Terrasi F. 
Published: April 2022

AbstractCarbon fusion reactions $$^{12}$$

12

C($$^{12}$$

12

C,p)$$^{23}$$

23

Na and $$^{12}$$

12

C($$^{12}$$

12

C,$$\alpha $$
α
)$$^{20}$$

20

Ne play a key role in the evolution of massive stars and in explosive scenarios such as type-Ia supernovae and super-bursts in binary stars. A direct determination of their cross sections is extremely challenging and discrepancies exist between different data sets in the literature. Here we report the results of a direct measurement performed at the CIRCE Tandem Accelerator Laboratory in Caserta (Italy), using $$\varDelta E-E$$

Δ
E
-
E

detectors for unambiguous charge identification. Cross sections were measured in the energy range $$E_{\mathrm{c.m.}} =2.51{-}4.36$$

E

c
.
m
.

=
2.51
-
4.36

MeV with energy steps between 10 and 25 keV in the centre of mass. To our knowledge these represent the finest energy steps to date. Results are presented in the form of partial and summed astrophysical $${\tilde{S}}$$

S
~

-factors for individual proton- and $$\alpha $$
α
-particle channels. Branching ratios of individual proton- and $$\alpha $$
α
-particle groups were found to vary significantly with energy. Angular distributions, albeit limited to three angles, were also found to be non-isotropic, which could be a potential explanation for the discrepancies observed among different data sets. Further efforts are ongoing to extend measurements to lower energies.
Hydrodynamic attractors in heavy ion collisions: a review
Authors: Soloviev Alexander 
Published: April 2022

AbstractA review of the recent progress of relativistic hydrodynamic attractors is presented, with a focus on applications in heavy ion collisions and the quark gluon plasma. Pedagogical introductions to the effective descriptions relevant for attractors in high energy physics, namely hydrodynamics, holography and kinetic theory, are followed by highlights of some recent advances.
Caspase 9b Drives Cellular Transformation, Lung Inflammation, and Lung Tumorigenesis
Authors: Kim Minjung , Vu Ngoc T. , Wang Xue , Bulut Gamze B. , Wang Min-Hsuan , Uram-Tuculescu Cora , Pillappa Raghavendra , Kim Sungjune , Chalfant Charles E. 
Published: April 2022

Abstract

Caspase 9 undergoes alternative splicing to produce two opposing isoforms: proapoptotic Caspase 9a and pro-survival Caspase 9b (C9b). Previously, our laboratory reported that C9b is expressed in majority of non–small cell lung cancer tumors and directly activates the NF-κB pathway. In this study, the role of C9b in activation of the NF-κB pathway in vivo, lung inflammation and immune responses, and lung tumorigenesis were examined. Specifically, a transgenic mouse model expressing human C9b in the lung pneumocytes developed inflammatory lung lesions, which correlated with enhanced activation of the NF-κB pathway and increased influx of immunosuppressive myeloid-derived suppressor cells in contrast to wild-type mice. C9b mice presented with facial dermatitis, a thickened and disorganized dermis, enhanced collagen depth, and increased serum levels of IL6. C9b mice also developed spontaneous lung tumors, and C9b cooperated with oncogenic KRAS in lung tumorigenesis. C9b expression also cooperated with oncogenic KRAS and p53 downregulation to drive the full cell transformation of human bronchial epithelial cells (e.g., tumor formation).

Implications:
Our findings show that C9b can directly activate NF-κB pathway in vivo to modulate lung inflammation, immune cell influx, and peripheral immune responses, which demonstrates that C9b is key factor in driving cell transformation and lung tumorigenesis.
Strategies to Identify and Recruit Women at High Risk for Breast Cancer to a Randomized Controlled Trial of Web-based Decision Support Tools
Authors: McGuinness Julia E. , Bhatkhande Gauri , Amenta Jacquelyn , Silverman Thomas , Mata Jennie , Guzman Ashlee , He Ting , Dimond Jill , Jones Tarsha , Kukafka Rita , Crew Katherine D. 
Published: April 2022

Abstract

We evaluated strategies to identify and recruit a racially/ethnically diverse cohort of women at high-risk for breast cancer to a randomized controlled trial (RCT). We enrolled 300 high-risk women and 50 healthcare providers to a RCT of standard educational materials alone or in combination with web-based decision support tools. We implemented five strategies to identify high-risk women: (i) recruitment among patients previously enrolled in a study evaluating breast cancer risk; (ii) automated breast cancer risk calculation using information extracted from the electronic health record (EHR); (iii) identification of women with atypical hyperplasia or lobular carcinoma in situ (LCIS) using International Classification of Diseases (ICD)-9/10 diagnostic codes; (iv) clinical encounters with enrolled healthcare providers; (v) recruitment flyers/online resources. Breast cancer risk was calculated using either the Gail or Breast Cancer Surveillance Consortium (BCSC) models. We identified 6,229 high-risk women and contacted 3,459 (56%), of whom 17.2% were identified from prior study cohort, 37.5% through EHR risk information, 14.8% with atypical hyperplasia/LCIS, 29.0% by clinical encounters, and 1.5% through recruitment flyers. Women from the different recruitment sources varied by age and 5-year invasive breast cancer risk. Of 300 enrolled high-risk women, 44.7% came from clinical encounters and 27.3% from prior study cohort. Comparing enrolled with not-enrolled participants, there were significant differences in mean age (57.2 vs. 59.1 years), proportion of non-Whites (41.5% vs. 54.8%), and mean 5-year breast cancer risk (3.0% vs. 2.3%). We identified and successfully recruited diverse high-risk women from multiple sources. These strategies may be implemented in future breast cancer chemoprevention trials.

Prevention Relevance:
We describe five strategies to identify and successfully recruit a large cohort of racially/ethnically diverse high-risk women from multiple sources to a randomized controlled trial evaluating interventions to increase chemoprevention uptake. Findings could inform recruitment efforts for future breast cancer prevention trials to increase recruitment yield of high-risk women.
Precision Combination Therapies Based on Recurrent Oncogenic Coalterations
Authors: Li Xubin , Dowling Elisabeth K. , Yan Gonghong , Dereli Zeynep , Bozorgui Behnaz , Imanirad Parisa , Elnaggar Jacob H. , Luna Augustin , Menter David G. , Pilié Patrick G. , Yap Timothy A. , Kopetz Scott , Sander Chris , Korkut Anil 
Published: April 2022

Abstract

Cancer cells depend on multiple driver alterations whose oncogenic effects can be suppressed by drug combinations. Here, we provide a comprehensive resource of precision combination therapies tailored to oncogenic coalterations that are recurrent across patient cohorts. To generate the resource, we developed Recurrent Features Leveraged for Combination Therapy (REFLECT), which integrates machine learning and cancer informatics algorithms. Using multiomic data, the method maps recurrent coalteration signatures in patient cohorts to combination therapies. We validated the REFLECT pipeline using data from patient-derived xenografts, in vitro drug screens, and a combination therapy clinical trial. These validations demonstrate that REFLECT-selected combination therapies have significantly improved efficacy, synergy, and survival outcomes. In patient cohorts with immunotherapy response markers, DNA repair aberrations, and HER2 activation, we have identified therapeutically actionable and recurrent coalteration signatures. REFLECT provides a resource and framework to design combination therapies tailored to tumor cohorts in data-driven clinical trials and preclinical studies.

Significance:
We developed the predictive bioinformatics platform REFLECT and a multiomics- based precision combination therapy resource. The REFLECT-selected therapies lead to significant improvements in efficacy and patient survival in preclinical and clinical settings. Use of REFLECT can optimize therapeutic benefit through selection of drug combinations tailored to molecular signatures of tumors.
See related commentary by Pugh and Haibe-Kains, p. 1416.
This article is highlighted in the In This Issue feature, p. 1397
The Tankyrase Inhibitor OM-153 Demonstrates Antitumor Efficacy and a Therapeutic Window in Mouse Models
Authors: Brinch Shoshy A. , Amundsen-Isaksen Enya , Espada Sandra , Hammarström Clara , Aizenshtadt Aleksandra , Olsen Petter A. , Holmen Lone , Høyem Merete , Scholz Hanne , Grødeland Gunnveig , Sowa Sven T. , Galera-Prat Albert , Lehtiö Lari , Meerts Ilonka A.T.M. , Leenders Ruben G.G. , Wegert Anita , Krauss Stefan , Waaler Jo 
Published: April 2022

The catalytic enzymes tankyrase 1 and 2 (TNKS1/2) alter protein turnover by poly-ADP-ribosylating target proteins, which earmark them for degradation by the ubiquitin–proteasomal system. Prominent targets of the catalytic activity of TNKS1/2 include AXIN proteins, resulting in TNKS1/2 being attractive biotargets for addressing of oncogenic WNT/β-catenin signaling. Although several potent small molecules have been developed to inhibit TNKS1/2, there are currently no TNKS1/2 inhibitors available in clinical practice. The development of tankyrase inhibitors has mainly been disadvantaged by concerns over biotarget-dependent intestinal toxicity and a deficient therapeutic window. Here we show that the novel, potent, and selective 1,2,4-triazole–based TNKS1/2 inhibitor OM-153 reduces WNT/β-catenin signaling and tumor progression in COLO 320DM colon carcinoma xenografts upon oral administration of 0.33–10 mg/kg twice daily. In addition, OM-153 potentiates anti–programmed cell death protein 1 (anti–PD-1) immune checkpoint inhibition and antitumor effect in a B16-F10 mouse melanoma model. A 28-day repeated dose mouse toxicity study documents body weight loss, intestinal damage, and tubular damage in the kidney after oral–twice daily administration of 100 mg/kg. In contrast, mice treated oral–twice daily with 10 mg/kg show an intact intestinal architecture and no atypical histopathologic changes in other organs. In addition, clinical biochemistry and hematologic analyses do not identify changes indicating substantial toxicity. The results demonstrate OM-153–mediated antitumor effects and a therapeutic window in a colon carcinoma mouse model ranging from 0.33 to at least 10 mg/kg, and provide a framework for using OM-153 for further preclinical evaluations.Significance:This study uncovers the effectiveness and therapeutic window for a novel tankyrase inhibitor in mouse tumor models.
Epigenetic Upregulation of H19 and AMPK Inhibition Concurrently Contribute to S-Adenosylhomocysteine Hydrolase Deficiency-Promoted Atherosclerotic Calcification
Authors: Dai Xin , Liu Si , Cheng Lokyu , Huang Ting , Guo Honghui , Wang Dongliang , Xia Min , Ling Wenhua , Xiao Yunjun 
Published: April 2022

Background:
S-adenosylhomocysteine (SAH) is a risk factor of cardiovascular disease; inhibition of SAH hydrolase (SAHH) results in SAH accumulation and induces endothelial dysfunction and atherosclerosis. However, the effect and mechanism of SAHH in atherosclerotic calcification is still unclear. We aimed to explore the role and mechanism of SAHH in atherosclerotic calcification.

Methods:
The relationship between SAHH and atherosclerotic calcification was investigated in patients with coronary atherosclerotic calcification. Different in vivo genetic models were used to examine the effect of SAHH deficiency on atherosclerotic calcification. Human aortic and murine vascular smooth muscle cells (VSMCs) were cultured to explore the underlying mechanism of SAHH on osteoblastic differentiation of VSMCs.

Results:
The expression and activity of SAHH were decreased in calcified human coronary arteries and inversely associated with coronary atherosclerotic calcification severity, whereas plasma SAH and total homocysteine levels were positively associated with coronary atherosclerotic calcification severity. Heterozygote knockout of SAHH promoted atherosclerotic calcification. Specifically, VSMC-deficient but not endothelial cell–deficient or macrophage-deficient SAHH promoted atherosclerotic calcification. Mechanistically, SAHH deficiency accumulated SAH levels and induced H19-mediated Runx2 (runt-related transcription factor 2)-dependent osteoblastic differentiation of VSMCs by inhibiting DNMT3b (DNA methyltransferase 3b) and leading to hypomethylation of the H19 promoter. On the contrary, SAHH deficiency resulted in lower intracellular levels of adenosine and reduced AMPK (AMP-activated protein kinase) activation. Adenosine supplementation activated AMPK and abolished SAHH deficiency–induced expression of H19 and Runx2 and osteoblastic differentiation of VSMCs. Finally, AMPK activation by adenosine inhibited H19 expression by inducing Sirt1 (sirtuin-1)-mediated histone H3 hypoacetylation and DNMT3b-mediated hypermethylation of the H19 promoter in SAHH deficiency VSMCs.

Conclusions:
We have confirmed a novel correlation between SAHH deficiency and atherosclerotic calcification and clarified a new mechanism that epigenetic upregulation of H19 and AMPK inhibition concurrently contribute to SAHH deficiency–promoted Runx2-dependent atherosclerotic calcification.