bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining Comprehensive Disease Control for Use as a Treatment Target for Ulcerative Colitis in Clinical Practice: International Delphi Consensus Recommendations
Authors: Schreiber Stefan , Danese Silvio , Dignass Axel , Domènech Eugeni , Fantini Massimo C , Ferrante Marc , Halfvarson Jonas , Hart Ailsa , Magro Fernando , Lees Charlie W , Leone Salvo , Pierik Marieke J , Peters Michele , Field Polly , Fishpool Helen , Peyrin-Biroulet Laurent 
Published: August 2023

Abstract

Background and Aims
Treatment of ulcerative colitis [UC] requires a patient-centric definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative, we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process.

Methods
The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before Round 3. Consensus was met if ≥67% of the panel agreed. Statements without consensus in Rounds 1 and 2 were revised or discarded after Round 3.

Results
The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials [rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use] with additional patient-reported symptoms [bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance]. The panel agreed on scoring systems and thresholds for many aspects.

Conclusions
Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multicomponent tool and will adopt comprehensive disease control as a treatment target in clinical practice and trials.
Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis
Authors: Ranjan Mukesh Kumar , Kumar Peeyush , Vuyyuru Sudheer Kumar , Kante Bhaskar , Mundhra Sandeep K , Golla Rithvik , Virmani Shubi , Sharma Raju , Sahni Peush , Das Prasenjit , Kalaivani Mani , Upadhyay Ashish Datt , Makharia Govind , Kedia Saurabh , Ahuja Vineet 
Published: August 2023

Abstract

Background and Aims
Thiopurines are viable option for the treatment of inflammatory bowel disease [IBD] in resource-limited countries. However, data on the effect of disease duration at thiopurines initiation on long-term effectiveness are limited.

Method
We performed a propensity matched analysis of a retrospective cohort of patients with ulcerative colitis [UC] and Crohn’s disease [CD]. Patients initiated on thiopurines early in the disease course [≤2 years] were compared with those started late [&gt;2 years]. Effectiveness was defined as no requirement for hospitalisation, anti-tumour necrosis factor [TNF] agents, or surgery, and minimum steroid requirement [≤1 steroid course in 2 years] during follow-up.

Results
A total of 988 [UC: 720, CD: 268] patients were included (male: 665 [60.8%], median age: 40 [32–51] years, median follow-up: 40 [19–81] months). Overall effectiveness at 5 and 10 years was 79% and 72% in UC, and 69% and 63% in CD, respectively. After propensity score matching, there was no difference in 5- and 10-year effectiveness between early and late thiopurine initiation groups either for UC [81% and 80% vs 82% and 74%; p = 0.92] or CD [76% and 66% vs 72% and 51%, p = 0.32]. Male sex for UC (negative: hazard ratio [HR]: 0.67, 95% confidence interval [CI): 0.45–0.97; p = 0.03), and ileal involvement [positive: HR: 3.03, 95% CI: 1.32–6.71; p = 0.008], steroid-dependent disease [positive: HR: 2.70, 95% CI: 1.26–5.68; p = 0.01] and adverse events [negative: HR: 0.47, 95% CI:0.27–0.80; p = 0.005] for CD were predictors of thiopurine effectiveness.

Conclusion
Thiopurines have sustained long-term effectiveness in both UC and CD. However, early thiopurine initiation had no better effect on long-term disease outcome compared with late initiation.
Clinical considerations during spontaneous coronary artery dissection in the post-partum period: a case report
Authors: Schamroth Pravda Nili , Houri Ohad , Kornowski Ran , Porter Avital 
Published: August 2023

Abstract

Background
Spontaneous coronary artery dissection (SCAD) is a common and under-recognized cause of myocardial infarction during the post-partum period.

Case summary
We report a case of a young women presenting with chest pain in the post-partum period. Her clinical appearance was that of a myocardial infarction, and angiography was indicative of a Type 2 SCAD. The patients had persistent chest pain, reduced left ventricular function, and critical left anterior descending artery stenosis. Percutaneous coronary intervention was done with caution. Shared decision-making with the patient helped guide the medical treatment plan and follow-up.

Discussion
We discuss the clinical considerations surrounding the management of this patient.
Testing an Intervention to Improve Posthospital Outcomes in Persons Living With Dementia and Their Family Care Partners
Authors: Boltz Marie , Mogle Jacqueline , Kuzmik Ashley , BeLue Rhonda , Leslie Douglas , Galvin James E , Resnick Barbara 
Published: August 2023

Abstract

Background and Objectives
Hospitalized persons living with dementia are at risk for functional decline, behavioral symptoms of distress, and delirium, all persisting in the postacute period. In turn, family care partners (FCPs) experience increased anxiety and lack of preparedness for caregiving, compounding existing strain and burden. Family-centered Function-focused Care (Fam-FFC) purposefully engages FCPs in assessment, decision-making, care delivery, and evaluation of function-focused care during and after hospitalization (within 48 hours of discharge, weekly telephone calls for a total of 7 additional weeks, then monthly for 4 months). The objective of this study was to test the efficacy of Fam-FFC.

Research Design and Methods
A cluster randomized controlled trial included 455 dyads of persons living with dementia and FCPs in 6 medical units in 3 hospitals. Patient outcomes included return to baseline physical function, behavioral symptoms of distress, depressive symptoms, and delirium severity. Family care partner measures included preparedness for caregiving, anxiety, strain, and burden.

Results
Multilevel level modeling demonstrated that the likelihood of returning to baseline function across time for Fam-FFC participants was twice that of the control group by the end of 6 months (OR = 2.4, p = .01, 95% CI 1.2–4.7). Family-centered Function-focused Care was also associated with fewer symptoms of distress (b = −1.1, SE = 0.56, p = .05) but no differences in the amount of moderate physical activity, depressive symptoms, and delirium severity. Preparedness for caregiving increased significantly only from 2 to 6 months (b = 0.89, SE = 0.45, d = 0.21, overall p = .02) in the intervention group, with no group differences in anxiety, strain, and burden.

Discussion and Implications
Family-centered Function-focused Care may help prevent some of the postacute functional decline and behavioral symptoms in hospitalized persons living with dementia. Further research is needed to promote sustained improvements in these symptoms with more attention to the postacute needs of the care partner.
Promoter variations in DBR2-like affect artemisinin production in different chemotypes of Artemisia annua
Authors: Wang Xingwen , Wu Lan , Xiang Li , Gao Ranran , Yin Qinggang , Wang Mengyue , Liu Zhaoyu , Leng Liang , Su Yanyan , Wan Huihua , Ma Tingyu , Chen Shilin , Shi Yuhua 
Published: August 2023

Abstract
Artemisia annua is the only known plant source of the potent antimalarial artemisinin, which occurs as the low- and high-artemisinin producing (LAP and HAP) chemotypes. Nevertheless, the different mechanisms of artemisinin producing between these two chemotypes were still not fully understood. Here, we performed a comprehensive analysis of genome resequencing, metabolome, and transcriptome data to systematically compare the difference in the LAP chemotype JL and HAP chemotype HAN. Metabolites analysis revealed that 72.18% of sesquiterpenes was highly accumulated in HAN compared to JL. Integrated omics analysis found a DBR2-Like (DBR2L) gene may be involved in artemisinin biosynthesis. DBR2L was highly homologous with DBR2, belonged to ORR3 family, and had the DBR2 activity of catalyzing artemisinic aldehyde to dihydroartemisinic aldehyde. Genome resequencing and promoter cloning revealed that complicated variations existed in DBR2L promoters among different varieties of A. annua and were clustered into three variation types. The promoter activity of diverse variant types showed obvious differences. Furthermore, the core region (−625 to 0) of the DBR2L promoter was identified and candidate transcription factors involved in DBR2L regulation were screened. Thus, the result indicates that DBR2L is another key enzyme involved in artemisinin biosynthesis. The promoter variation in DBR2L affects its expression level, and thereby may result in the different yield of artemisinin in varieties of A. annua. It provides a novel insight into the mechanism of artemisinin-producing difference in LAP and HAP chemotypes of A. annua, and will assist in a high yield of artemisinin in A. annua.
Segmentectomy for cancer control in radiologically pure-solid clinical stage IA3 lung cancer
Authors: Kamigaichi Atsushi , Mimae Takahiro , Tsubokawa Norifumi , Miyata Yoshihiro , Adachi Hiroyuki , Shimada Yoshihisa , Ito Hiroyuki , Ikeda Norihiko , Okada Morihito 
Published: August 2023

Abstract

OBJECTIVES
This study aimed to compare cancer control after segmentectomy and lobectomy in patients with radiologically pure-solid clinical stage IA3 non-small-cell lung cancer (NSCLC).

METHODS
Patients with radiologically pure-solid clinical stage IA3 NSCLC who underwent lobectomy or segmentectomy at 3 institutions between 2010 and 2019 were identified. We estimated propensity scores to adjust for confounding variables regarding tumour malignancy, including age, sex, smoking history, tumour size, maximum standardized uptake value on 18F-fluorodeoxyglucose positron emission tomography, lymph node dissection, histological type and lymphatic, vascular and pleural invasion. Cumulative incidence of recurrence (CIR) was evaluated as a primary end point.

RESULTS
Among 412 patients, postoperative recurrence occurred in 7 of 44 patients (15.9%) undergoing segmentectomy, and 71 of 368 patients (19.3%) undergoing lobectomy. CIR was comparable between patients undergoing segmentectomy (5-year rate, 21.9%) and those undergoing lobectomy (5-year rate, 20.8%; P = 0.88). Locoregional recurrence did not differ between patients undergoing segmentectomy (6.8%) and those undergoing lobectomy (9.0%). In multivariable analysis, segmentectomy (versus lobectomy) was not identified as an independent prognostic factor for CIR (hazard ratio, 1.045; 95% confidence interval, 0.475–2.298; P = 0.91). In propensity score matching of 40 pairs, CIR was not significantly different between patients undergoing segmentectomy (5-year rate, 20.7%) and those undergoing lobectomy (5-year rate, 18.4%; P = 0.81).

CONCLUSIONS
Cancer control may be comparable between segmentectomy and lobectomy in patients with radiologically pure-solid clinical stage IA3 NSCLC. Further studies are warranted to clarify the survival benefits of segmentectomy in these patients.
Linear and Quadratic Chabauty for Affine Hyperbolic Curves
Authors: Leonhardt Marius , Lüdtke Martin , Müller J Steffen 
Published: August 2023

Abstract
We give sufficient conditions for finiteness of linear and quadratic refined Chabauty–Kim loci of affine hyperbolic curves. We achieve this by constructing depth $\leq 2$ quotients of the fundamental group, following a construction of Balakrishnan–Dogra in the projective case. We also apply Betts’ machinery of weight filtrations to give unconditional explicit upper bounds on the number of $S$-integral points when our conditions are satisfied.
Evolution of Spatial Risk of Malaria Infection After a Pragmatic Chemoprevention Program in Response to Severe Flooding in Rural Western Uganda
Authors: Xu Erin , Goel Varun , Baguma Emmanuel , Ayebare Emmanuel , Hollingsworth Brandon D , Brown-Marusiak Amanda , Giandomenico Dana , Reyes Raquel , Ntaro Moses , Mulogo Edgar M , Boyce Ross M 
Published: August 2023

Abstract

Background
Malaria epidemics result from extreme precipitation and flooding, which are increasing with global climate change. Local adaptation and mitigation strategies will be essential to prevent excess morbidity and mortality.

Methods
We investigated the spatial risk of malaria infection at multiple timepoints after severe flooding in rural western Uganda employing longitudinal household surveys measuring parasite prevalence and leveraging remotely sensed information to inform spatial models of malaria risk in the 3 months after flooding.

Results
We identified clusters of malaria risk emerging in areas (1) that showed the greatest changes in Normalized Difference Vegetation Index from pre- to postflood and (2) where residents were displaced for longer periods of time and had lower access to long-lasting insecticidal nets, both of which were associated with a positive malaria rapid diagnostic test result. The disproportionate risk persisted despite a concurrent chemoprevention program that achieved high coverage.

Conclusions
The findings enhance our understanding not only of the spatial evolution of malaria risk after flooding, but also in the context of an effective intervention. The results provide a “proof of concept” for programs aiming to prevent malaria outbreaks after flooding using a combination of interventions. Further study of mitigation strategies—and particularly studies of implementation—is urgently needed.
Mitochondrial transport of catalytic RNAs and targeting of the organellar transcriptome in human cells
Authors: Głodowicz Paweł , Kuczyński Konrad , Val Romain , Dietrich André , Rolle Katarzyna 
Published: August 2023

Abstract
Mutations in the small genome present in mitochondria often result in severe pathologies. Different genetic strategies have been explored, aiming to rescue such mutations. A number of these strategies were based on the capacity of human mitochondria to import RNAs from the cytosol and designed to repress the replication of the mutated genomes or to provide the organelles with wild-type versions of mutant transcripts. However, the mutant RNAs present in mitochondria turned out to be an obstacle to therapy and little attention has been devoted so far to their elimination. Here, we present the development of a strategy to knockdown mitochondrial RNAs in human cells using the transfer RNA-like structure of Brome mosaic virus or Tobacco mosaic virus as a shuttle to drive trans-cleaving ribozymes into the organelles in human cell lines. We obtained a specific knockdown of the targeted mitochondrial ATP6 mRNA, followed by a deep drop in ATP6 protein and a functional impairment of the oxidative phosphorylation chain. Our strategy provides a powerful approach to eliminate mutant organellar transcripts and to analyse the control and communication of the human organellar genetic system.
Quercetin Mitigates Oxidative Stress, Inflammation, Apoptosis, and Histopathological Alterations Induced by Chronic Titanium Dioxide Nanoparticle Exposure in the Rat Spleen
Authors: Jaber Fatima A 
Published: August 2023

AbstractTitanium dioxide nanoparticles (nano-TiO2) have become widespread but are accompanied by various health concerns. Quercetin (QT), a naturally occurring flavonoid in fruits and vegetables, exhibits potent antioxidant properties. This research examined the toxic impacts of nano-TiO2 on the structure and function of the spleen in adult male rats and assessed the possible protective effects of QT. A set of randomly grouped rats was established, consisting of a control group, a QT group (50 mg/kg/day), a nano-TiO2 group (300 mg/kg/day), and a QT-nano-TiO2 group. These substances were orally administered to the respective groups for 90 days. Nano-TiO2 significantly induced oxidative stress in the spleen, leading to reduced levels of serum immunoglobulins. Additionally, there was a notable increase in the expression of apoptotic markers and proinflammatory cytokines. These biochemical disturbances were accompanied by morphological changes in the spleens of rats exposed to nano-TiO2. However, coadministration of QT and nano-TiO2 effectively mitigated most nano-TiO2-induced alterations in the spleen, including apoptotic and proinflammatory responses, antioxidant imbalance, serum immunoglobulin levels, and histopathological changes. It can be concluded that QT has the potential to function as a protective agent against the detrimental impacts of nano-TiO2 on the spleen by improving the antioxidant defense mechanism and modulating the apoptotic and inflammatory responses.
A systematic review of targeted therapy for vestibular schwannoma in patients with NF2-related schwannomatosis
Authors: Chiranth Shivani , Langer Seppo W , Poulsen Hans Skovgaard , Urup Thomas 
Published: August 2023

Abstract

Background
One of the hallmarks of NF2-related Schwannomatosis (NF2-related SWN) is bilateral vestibular schwannomas (VS) that can cause progressive hearing impairment in patients. This systematic review was performed to investigate the efficacy and toxicity of tested targeted agents.

Methods
The systematic search was conducted on PubMed and EMBASE Ovid databases from inception to October 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The incidence of outcomes in studies involving bevacizumab and other targeted therapies was extracted. The bevacizumab results were pooled, and 95% confidence intervals (95% CI) were calculated.

Results
Sixteen studies (8 prospective and 8 retrospective) testing 6 drugs were selected out of 721 search results. There were 10 studies concerning bevacizumab, with a total of 200 patients. The pooled radiographic response rate (RR) was 38% (95% CI: 31 – 45%) and the pooled hearing response rate (HR) was 45% (95% CI: 36 - 54%). The most frequent bevacizumab-related toxicities were hypertension and menorrhagia. Of other targeted therapies showing activity, lapatinib had a RR of 6% and a HR of 31%. A VEGFR vaccine showed RR in 29% and HR in 40% of patients. Both agents had a manageable safety profile.

Conclusions
Bevacizumab, in comparison to other targeted agents, showed the highest efficacy. Lower dosage of bevacizumab shows comparable efficacy and may reduce toxicity. Other targeted agents, administered alone or as combination therapy, have the potential to improve outcomes for VS in patients with NF2-related SWN, but future clinical studies are needed.
Phase evolution and enhanced room temperature piezoelectric properties response of lead-free Ru-doped BaTiO3 ceramic
Authors: Brajesh Kumar , Ranjan Sudhir , Garg Ashish 
Published: August 2023

Abstract
Recent years have witnessed considerable work on the development of lead-free piezoelectric ceramic materials and their structure–property correlations. The development of piezo response is a strong function of phase evolution in these materials. In this work, we report the effect of Ru doping and consequent phase evolution on the maximization of piezoelectric response of polycrystalline lead-free barium titanate, depicted as Ba(RuxTi1-x)O3 (BRT). The samples were prepared in a narrow compositional range of 0 ≤ x ≤ 0.03 using the conventional solid-state reaction method. Ru doping increases the leakage current of BaTiO3 samples attributed to increased oxygen vacancy concentration due to substitution of Ti4+ by Ru3+. Detailed structural analysis reveals that samples exhibiting coexistence of tetragonal (space group: P4mm) and orthorhombic (space group: Amm2) structured phases near room temperature reveal relatively enhanced piezoelectric properties. The BRT sample with Ru content of 2 mol% yields a maximum longitudinal piezoelectric coefficient, d33 of ∼269 pC/N, a high strain value of 0.16% with a large remnant polarization of ∼19 µC/cm2 and a coercive field of 5.8 kV/cm. We propose that the ‘4d’ orbital of Ruthenium plays a crucial role in improving the functional properties and in decreasing the ferroelectric Curie temperature. Our work provides clues into tailoring the phase evolution for designing lead-free piezoelectric materials with enhanced piezoelectric properties.
Effect of distance to tertiary centre on enrolment of paediatric patients with relapsed or refractory cancer on early phase clinical trials in British Columbia
Authors: D’Alessandro Paul R , Bone Jeffrey N , Davis Jessica F , Potts James E , Deyell Rebecca J 
Published: August 2023

Abstract

Objectives
Access to early phase trials for children with relapsed, refractory or progressive (RRPD) cancer is limited in Canada. Patients and families face barriers to access trials, which are poorly understood. The aims of this study were to assess availability of early phase trials and examine the impact of distance from home to study centre on trial enrolment among paediatric oncology patients with RRPD.

Methods
Oncology patients ≤18 years at diagnosis who later had RRPD were identified retrospectively via registry at the only quaternary paediatric oncology centre in British Columbia (BC). We determined if distance to home, as calculated using geocoding software, was predictive of trial offer or enrolment.

Results
Between January 2015 and July 2021, 266 patients experienced 396 RRPD events. Seventy-five patients (28.2%) were eligible for an early phase trial at least once. At first eligible event, 61 patients (22.9%) were offered trial (median age 11.8 years; 69.0% male; 46.0% with CNS tumour) and thirty patients (11.3%) enrolled. Distance was not associated with odds of offer (OR 1.01, CI 0.98 to 1.05) or enrolment (OR 0.99, CI 0.95 to 1.03) on univariate or multivariable analysis adjusted for sex and disease (OR 0.93, CI 0.86 to 1.00). For offered patients, 2-year event-free survival (EFS) and overall survival (OS) were 39.1% (CI 28.0% to 54.8%) and 51.8% (CI 39.9% to 67.2%), respectively. EFS/OS did not differ with distance or enrolment, but varied by disease (EFS P = 0.002, OS P &lt; 0.0001).

Conclusions
Children in BC with cancer and RRPD have limited access to early phase trials. Distance was not predictive of enrolment, suggesting that families travel to access therapy.