bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coping strategies used by families in Indonesia when caring for patients with mental disorders post-pasung, based on a case study approach
Authors: Yunita Fildzah Cindra , Yusuf Ah , Nihayati Hanik Endang , Hilfida Nurullia Hanum 
Published: February 2020

BackgroundTreatment of post-pasung(physical restraint) patients with mental disorders has become a new problem in Indonesia in its effort to free the country from the physical restraint programme. Problems emerge when the patient returns to the family and society at large, and families that refuse to allow the patient to come back home risk the possibility that the patient may eventually become a psychotic vagrant.AimsTo determine the appearance of families taking care of patients with mental disorders post-pasung.MethodThis study was qualitative research using a case study approach. The number of participants from six families was selected by purposive sampling. Collecting data was done by in-depth interview, and analysed thematically using Colaizzi steps.ResultsThe results showed that families coping when taking care of patients with mental disorders post-pasungcomprise seven themes. The seven themes are formed by four categories, 19 sub-themes and 32 sections.DiscussionThe appearance of coping was the overall description of coping in the form of strategic process stages, the support of coping and meaning for what the families feel when they are taking care of a patient with a mental disorder post-pasung. The appearance of coping showed how the family chooses the mechanisms of coping to deal with stress and crisis.ConclusionThe coping mechanisms that families use when taking care of a patient with a mental disorder post-pasungwere formed through stages of a strategic process. Families need coping strengthening interventions to provide optimal care for patients with mental disorders post-pasung.
Prognosis of pneumonia in patients with rheumatoid arthritis: the role of medication and disease activity prior to admission a population-based cohort study
Authors: Holland-Fischer Mette , Thomsen Reimar W , Tarp Ulrik , Nørgaard Mette 
Published: February 2020

ObjectivePatients with rheumatoid arthritis (RA) experience an increased risk of infections, but the prognosis of infections is unclear. We examined if patients with RA have worse outcomes from pneumonia than non-RA individuals.MethodsIn a population-based cohort study, we computed 90-day mortality rates and crude and adjusted HRs comparing pneumonia patients with and without RA. Among patients with RA, we evaluated prognostic effects of RA medications including prednisolone and disease activity as assessed by C reactive protein (CRP) or platelet levels measured 30–180 days before admission to avoid any influence from the subsequent infection.ResultsAmong 52 577 patients hospitalised for the first time with pneumonia, 1220 (2.3%) had RA. The 90-day mortality was 19.9% for patients with RA and 18.9% for non-RA patients (adjusted 90-day HR of 1.05 (95% CI 0.92 to 1.19)). Compared with CRP levels <8 mg/L, CRP levels ≥20 mg/L predicted increased mortality in patients with RA with adjusted 90-day HRs of 4.98 (95% CI 2.19 to 11.36). Compared with methotrexate monotherapy, both prednisolone (HR 1.43 (95% CI 0.91 to 2.22)) and no RA therapy (HR 1.35 (95% CI 0.85 to 2.14)) tended to increase 90-day mortality. Compared with patients who used prednisolone and had low CRP levels, high CRP predicted increased mortality both in patients who used prednisolone (HR 3.09, 95% CI 1.25 to 7.65) and those who did not (HR 2.35, 95% CI 0.94 to 5.87).ConclusionsOverall, RA does not increase mortality following hospitalisation for pneumonia. However, high RA disease activity prior to admission predicts increased pneumonia mortality in patients regardless of prednisolone use.
Effects of ustekinumab on spondylitis-associated endpoints in TNFi-naïve active psoriatic arthritis patients with physician-reported spondylitis: pooled results from two phase 3, randomised, controlled trials
Authors: Helliwell Philip S , Gladman Dafna D , Chakravarty Soumya D , Kafka Shelly , Karyekar Chetan S , You Yin , Campbell Kim , Sweet Kristen , Kavanaugh Arthur , Gensler Lianne S 
Published: February 2020

BackgroundThe interleukin-12/23p40-subunit-inhibitor ustekinumab significantly improved spondylitis-related symptoms through Week 24 in psoriatic arthritis (PsA) patients with peripheral arthritis and physician-reported spondylitis (PA-PRS) in PSUMMIT-1&2. We further evaluated ustekinumab’s effect on spondylitis-related endpoints in PSUMMIT-1&2 tumour necrosis factor-inhibitor (TNFi)-naïve patients with PA-PRS.MethodsPatients with active PsA (≥5 swollen and ≥5 tender joints, C-reactive-protein ≥ 3.0 mg/L) despite conventional (PSUMMIT-1&2) and/or prior TNFi (PSUMMIT-2) therapy received subcutaneous ustekinumab 45 mg, 90 mg or placebo (Week 0, Week 4, Week 16). Changes in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) neck/back/hip pain question (#2) and modified BASDAI (mBASDAI, excluding PA) scores and Ankylosing Spondylitis Disease Activity Score (ASDAS) responses were assessed at Weeks 12 and 24.ResultsThe pooled PSUMMIT-1&2, TNFi-naïve (n=747), PA-PRS (n=223) subset (158 with human-leucocyte-antigen (HLA)-B27results) presented with moderate-to-severe spondylitis-related symptoms (mean BASDAI-neck/back/hip pain-6.51, mBASDAI-6.54, BASDAI-6.51, ASDAS-3.81). Mean Week 24 changes were larger among ustekinumab than placebo-treated patients for both neck/back/hip pain (−1.99 vs −0.18) and mBASDAI (−2.09 vs −0.59). Improvements in neck/back/hip pain and fatigue appeared numerically greater inHLA-B27+thanHLA-B27–patients; those for other domains were generally consistent. Greater proportions of ustekinumab versus placebo-treated patients achieved ASDAS clinically important improvement at Week 24 (decrease ≥ 1.1; 49.6% vs 12.7%; nominal p<0.05).ConclusionsImprovements in BASDAI neck/back/hip pain and mBASDAI among ustekinumab-treated, TNFi-naïve, PsA patients with PA-PRS were clinically meaningful and consistent across assessment tools. Numerically greater improvements in neck/back/hip pain inHLA-B27+thanHLA-B27–patients, noted in the context of similar overall mBASDAI improvements between the subgroups, suggest ustekinumab may improve disease activity in TNFi-naïve PsA patients likely to exhibit axial disease.Clinical trial registration numbersPSUMMIT 1,NCT01009086; PSUMMIT 2,NCT01077362.
Clonal ZEB1-Driven Mesenchymal Transition Promotes Targetable Oncologic Antiangiogenic Therapy Resistance
Authors: Chandra Ankush , Jahangiri Arman , Chen William , Nguyen Alan T. , Yagnik Garima , Pereira Matheus P. , Jain Saket , Garcia Joseph H. , Shah Sumedh S. , Wadhwa Harsh , Joshi Rushikesh S. , Weiss Jacob , Wolf Kayla J. , Lin Jung-Ming G. , Müller Sören , Rick Jonathan W. , Diaz Aaron A. , Gilbert Luke A. , Kumar Sanjay , Aghi Manish K. 
Published: February 2020

Abstract

Glioblastoma (GBM) responses to bevacizumab are invariably transient with acquired resistance. We profiled paired patient specimens and bevacizumab-resistant xenograft models pre- and post-resistance toward the primary goal of identifying regulators whose targeting could prolong the therapeutic window, and the secondary goal of identifying biomarkers of therapeutic window closure. Bevacizumab-resistant patient specimens and xenografts exhibited decreased vessel density and increased hypoxia versus pre-resistance, suggesting that resistance occurs despite effective therapeutic devascularization. Microarray analysis revealed upregulated mesenchymal genes in resistant tumors correlating with bevacizumab treatment duration and causing three changes enabling resistant tumor growth in hypoxia. First, perivascular invasiveness along remaining blood vessels, which co-opts vessels in a VEGF-independent and neoangiogenesis-independent manner, was upregulated in novel biomimetic 3D bioengineered platforms modeling the bevacizumab-resistant microenvironment. Second, tumor-initiating stem cells housed in the perivascular niche close to remaining blood vessels were enriched. Third, metabolic reprogramming assessed through real-time bioenergetic measurement and metabolomics upregulated glycolysis and suppressed oxidative phosphorylation. Single-cell sequencing of bevacizumab-resistant patient GBMs confirmed upregulated mesenchymal genes, particularly glycoprotein YKL-40 and transcription factor ZEB1, in later clones, implicating these changes as treatment-induced. Serum YKL-40 was elevated in bevacizumab-resistant versus bevacizumab-naïve patients. CRISPR and pharmacologic targeting of ZEB1 with honokiol reversed the mesenchymal gene expression and associated stem cell, invasion, and metabolic changes defining resistance. Honokiol caused greater cell death in bevacizumab-resistant than bevacizumab-responsive tumor cells, with surviving cells losing mesenchymal morphology. Employing YKL-40 as a resistance biomarker and ZEB1 as a target to prevent resistance could fulfill the promise of antiangiogenic therapy.

Significance:
Bevacizumab resistance in GBM is associated with mesenchymal/glycolytic shifts involving YKL-40 and ZEB1. Targeting ZEB1 reduces bevacizumab-resistant GBM phenotypes.
Dual Oxidase-Induced Sustained Generation of Hydrogen Peroxide Contributes to Pharmacologic Ascorbate-Induced Cytotoxicity
Authors: Gibson Adrienne R. , O'Leary Brianne R. , Du Juan , Sarsour Ehab H. , Kalen Amanda L. , Wagner Brett A. , Stolwijk Jeffrey M. , Falls-Hubert Kelly C. , Alexander Matthew S. , Carroll Rory S. , Spitz Douglas R. , Buettner Garry R. , Goswami Prabhat C. , Cullen Joseph J. 
Published: February 2020

Abstract

Pharmacologic ascorbate treatment (P-AscH−, high-dose, intravenous vitamin C) results in a transient short-term increase in the flux of hydrogen peroxide that is preferentially cytotoxic to cancer cells versus normal cells. This study examines whether an increase in hydrogen peroxide is sustained posttreatment and potential mechanisms involved in this process. Cellular bioenergetic profiling following treatment with P-AscH− was examined in tumorigenic and nontumorigenic cells. P-AscH− resulted in sustained increases in the rate of cellular oxygen consumption (OCR) and reactive oxygen species (ROS) in tumor cells, with no changes in nontumorigenic cells. Sources for this increase in ROS and OCR were DUOX 1 and 2, which are silenced in pancreatic ductal adenocarcinoma, but upregulated with P-AscH− treatment. An inducible catalase system, to test causality for the role of hydrogen peroxide, reversed the P-AscH−–induced increases in DUOX, whereas DUOX inhibition partially rescued P-AscH−–induced toxicity. In addition, DUOX was significantly downregulated in pancreatic cancer specimens compared with normal pancreas tissues. Together, these results suggest that P-AscH−–induced toxicity may be enhanced by late metabolic shifts in tumor cells, resulting in a feed-forward mechanism for generation of hydrogen peroxide and induction of metabolic stress through enhanced DUOX expression and rate of oxygen consumption.

Significance:
A high dose of vitamin C, in addition to delivering an acute exposure of H2O2 to tumor cells, activates DUOX in pancreatic cancer cells, which provide sustained production of H2O2.
Extensive Clonal Branching Shapes the Evolutionary History of High-Risk Pediatric Cancers
Authors: Andersson Natalie , Bakker Bjorn , Karlsson Jenny , Valind Anders , Holmquist Mengelbier Linda , Spierings Diana C.J. , Foijer Floris , Gisselsson David 
Published: February 2020

Abstract

Darwinian evolution of tumor cells remains underexplored in childhood cancer. We here reconstruct the evolutionary histories of 56 pediatric primary tumors, including 24 neuroblastomas, 24 Wilms tumors, and 8 rhabdomyosarcomas. Whole-genome copy-number and whole-exome mutational profiling of multiple regions per tumor were performed, followed by clonal deconvolution to reconstruct a phylogenetic tree for each tumor. Overall, 88% of the tumors exhibited genetic variation among primary tumor regions. This variability typically emerged through collateral phylogenetic branching, leading to spatial variability in the distribution of more than 50% (96/173) of detected diagnostically informative genetic aberrations. Single-cell sequencing of 547 individual cancer cells from eight solid pediatric tumors confirmed branching evolution to be a fundamental underlying principle of genetic variation in all cases. Strikingly, cell-to-cell genetic diversity was almost twice as high in aggressive compared with clinically favorable tumors (median Simpson index of diversity 0.45 vs. 0.88; P = 0.029). Similarly, a comparison of multiregional sampling data from a total of 274 tumor regions showed that new phylogenetic branches emerge at a higher frequency per sample and carry a higher mutational load in high-risk than in low-risk tumors. Timelines based on spatial genetic variation showed that the mutations most influencing relapse risk occur at initiation of clonal expansion in neuroblastoma and rhabdomyosarcoma, whereas in Wilms tumor, they are late events. Thus, from an evolutionary standpoint, some high-risk childhood cancers are born bad, whereas others grow worse over time.

Significance:
Different pediatric cancers with a high risk of relapse share a common generic pattern of extensively branching evolution of somatic mutations.
A Noncanonical Role of Fructose-1, 6-Bisphosphatase 1 Is Essential for Inhibition of Notch1 in Breast Cancer
Authors: Lu Chao , Ren Chune , Yang Tingting , Sun Yonghong , Qiao Pengyun , Wang Dan , Lv Shijun , Yu Zhenhai 
Published: February 2020

Abstract

Breast cancer is a leading cause of death in women worldwide, but the underlying mechanisms of breast tumorigenesis remain unclear. Fructose-1, 6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis, was recently shown to be a tumor suppressor in breast cancer. However, the mechanisms of FBP1 as a tumor suppressor in breast cancer remain to be explored. Here we showed that FBP1 bound to Notch1 in breast cancer cells. Moreover, FBP1 enhanced ubiquitination of Notch1, further leading to proteasomal degradation via FBXW7 pathway. In addition, we found that FBP1 significantly repressed the transactivation of Notch1 in breast cancer cells. Functionally, Notch1 was involved in FBP1-mediated tumorigenesis of breast cancer cells in vivo and in vitro. Totally, these findings indicate that FBP1 inhibits breast tumorigenesis by regulating Notch1 pathway, highlighting FBP1 as a potential therapeutic target for breast cancer.

Implications:
We demonstrate FBP1 as a novel regulator for Notch1 in breast cancer.
A healthy sports club initiative in action in Ireland
Authors: Lane Aoife , Murphy Niamh , Donohoe Alex , Regan Colin 
Published: February 2020

Objective: The Gaelic Athletic Association (GAA) is part of the cultural fabric of Irish society with a club in almost every community nationwide. The aim of this project was to carry out a pilot evaluation of the GAA Healthy Club Project (HCP), which is a unique effort by a national governing body to include health as part of the core business of the organisation at grass roots level. Design: A pre–post intervention group only design was used across 18 clubs recruited to a pilot phase of the project. Setting: GAA grassroots sports clubs across Ireland. Methods: Twelve Healthy Club Officers completed a self-evaluation survey of their club at two time points to indicate the health promotion orientation of their club and the extent of health promotion activity in the club. Results: Data showed improvements in the health promotion orientation of clubs, from moderate to high health promoting overall and particular increases in policy and practice scores. This is likely due to the widespread appointment of Healthy Club Officers and the delivery of health-related initiatives in clubs. Conclusion: The impact of the project, while not demonstrable as an intervention effect at this stage, was real for the clubs involved. The GAA HCP is a novel way of carrying out health promotion in Ireland, serving as a meeting point between the ‘push of health’ and ‘pull of the sports club’.
Smectitic clays enriched with ferric ions for the rapid removal of anionic dyes in aqueous media
Authors: Rodrigues Itamar A. , Villalba Juan C. , Santos Maria J. , Melquiades Fábio L. , Anaissi Fauze J. 
Published: February 2020

AbstractSodium smectite clays were enriched with ferric ions (Argel-Fe and Volclay-Fe) to convert the surface charge of the clays from negative to positive and to use the clays in the discolouration of a synthetic effluent composed of seven anionic dyes (mixed from tartrazine, Brilliant Blue FCF and amaranth). The iron content increased from 5.99% to 11.02% for Argel-Fe and from 5.39% to 10.54% for Volclay-Fe. The efficiency of the discolouration of the anion dye mixture was evaluated by measuring the absorbance of the mixture at 562 nm, where the band with the greatest intensity was found. The contact time required for the system to reach equilibrium was ~5 min for both adsorbents. The kinetic adsorption data supported a pseudo-second-order kinetic model. The experimental data support the dual-site Langmuir–Freundlich isotherm model. The maximum adsorption capacities were 88.68 mg g–1for Argel-Fe and 392.21 mg g–1for Volclay-Fe. The enrichment of clays with Fe(III) added functionality to the clays and generated adsorbents with rapid adsorption abilities and high discolouration capacities.
Dual dependence on BCL2 and MCL1 in T-cell prolymphocytic leukemia
Authors: Smith Victoria M. , Lomas Oliver , Constantine Donna , Palmer Lianne , Schuh Anna H. , Bruce David , Gonchar Oksana , Macip Salvador , Jayne Sandrine , Dyer Martin J. S. , Eyre Toby A. 
Published: February 2020

Key Points
Treatment of relapsed refractory T-PLL with venetoclax monotherapy results in only transient and minor clinical responses. In vitro analyses pre- and postvenetoclax indicate dual dependence on BCL2 and MCL1; combined BCL2 and MCL1 inhibition are synergistic.
Gilteritinib is a clinically active FLT3 inhibitor with broad activity against FLT3 kinase domain mutations
Authors: Tarver Theodore C. , Hill Jason E. , Rahmat Leena , Perl Alexander E. , Bahceci Erkut , Mori Kenichi , Smith Catherine C. 
Published: February 2020

Abstract
Gilteritinib is the first FMS-like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitor (TKI) approved as monotherapy in acute myeloid leukemia with FLT3 internal tandem duplication and D835/I836 tyrosine kinase domain (TKD) mutations. Sequencing studies in patients have uncovered less common, noncanonical (NC) mutations in FLT3 and have implicated secondary TKD mutations in FLT3 TKI resistance. We report that gilteritinib is active against FLT3 NC and TKI resistance-causing mutations in vitro. A mutagenesis screen identified FLT3 F691L, Y693C/N, and G697S as mutations that confer moderate resistance to gilteritinib in vitro. Analysis of patients treated with gilteritinib revealed that 2/9 patients with preexisting NC FLT3 mutations responded and that secondary TKD mutations are acquired in a minority (5/31) of patients treated with gilteritinib. Four of 5 patients developed F691L mutations (all treated at &lt;200 mg). These studies suggest that gilteritinib has broad activity against FLT3 mutations and limited vulnerability to resistance-causing FLT3 TKD mutations, particularly when used at higher doses.
Effect of short-term inhalation of warm saline atomised gas on patients with non-cystic fibrosis bronchiectasis
Authors: Zhong Lihong , Xiong Ying , Zheng Zeguang , Liu Ni , Hu Jieying , Yang Feng , Chen Rongchang 
Published: February 2020

ObjectiveSecretion clearance is advocated in non-cystic fibrosis bronchiectasis, but is often neglected in clinical treatment. The present study aimed to investigate the effect of inhaled 0.9% normal saline by ultrasonic nebuliser with warming (UNW) in stable non-cystic fibrosis bronchiectasis patients with purulent sputum.Methods27 stable patients were enrolled in a randomised crossover trial comprising 3 months of daily UNW aerosol therapy compared with 3 months of daily oral expectorant treatment. The outcomes were quality of life (assessedviathe Leicester cough questionnaire (LCQ)), sputum characteristics, pulmonary function, 6-min walk distance (6MWD) and acute exacerbation frequency.ResultsCompared with baseline, the sputum viscosity, sputum colour, LCQ score and 6MWD were significantly improved with UNW (p<0.05), and the improvements in sputum colour, LCQ score, 6MWD and inspirational capacity with UNW were significantly better than those achievedviatreatment with oral expectorant (p<0.05). There were no significant differences between treatments in pulmonary function, sputum cytology classification and inflammatory factors of sputum.ConclusionUNW aerosol therapy in non-cystic fibrosis bronchiectasis has small yet significant benefits. However, UNW does not improve the degree of inflammation.
Routine neck ultrasound by respiratory physicians in the diagnosis and staging of patients with lung cancer and mediastinal lymphadenopathy: a prospective pilot study
Authors: Ahmed Mohammed , Daneshvar Cyrus , Breen David 
Published: February 2020

IntroductionCervical lymphadenopathy in lung cancer indicates advanced disease. The presence of mediastinal lymphadenopathy is commonly associated with involvement of neck lymph nodes and some studies suggest routine neck ultrasound (NUS) in this group of patients. We conducted a two-phase study looking at training a respiratory physician to perform ultrasound-guided neck lymph node aspiration in patients with suspected lung cancer.MethodsIn the first phase of the study, one of the authors underwent training in NUS according to predetermined criteria. The adequacy of sampling was prospectively recorded. In the second phase, consecutive patients with suspected lung cancer and mediastinal lymphadenopathy underwent NUS and sampling of abnormal lymph nodes. The outcomes were the adequacy of samples for pathological analysis and molecular analysis, prevalence of cervical lymphadenopathy, and change in stage.ResultsFollowing the period of training, 35 patients underwent neck node sampling with an overall adequacy of 88.6% (95% CI 78.1–99.1%). Cervical lymph node involvement was confirmed in 13 out of 30 patients with lung cancer (43.3%, 95% CI 25.5–62.6%). Further immunohistochemistry and molecular studies were possible in all patients when it was required (nine cases). NUS led to nodal upstaging in four out of 30 (13.3%) cases.ConclusionTraining a respiratory physician to perform NUS and needle sampling to an acceptable level is feasible. Benefits of embedding this procedure in lung cancer diagnosis and pathway staging need to be explored in further studies.