bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with potentially inappropriate prescriptions and barriers to medicines optimisation among older adults in primary care settings: a systematic review
Authors: Xu Zhijie , Liang Xujian , Zhu Yue , Lu Yiting , Ye Yuanqu , Fang Lizheng , Qian Yi 
Published: November 2021

ObjectiveTo identify factors that likely contribute to potentially inappropriate prescriptions (PIPs) among older adults in primary care settings, as well as barriers to medicines optimisation and recommended potential solutions.DesignSystematic review.Eligibility criteriaQuantitative studies that analysed the factors associated with PIPs among older adults (≥65 years) in primary care settings, and qualitative studies that explored perceived barriers and potential solutions to medicines optimisation for this population.Information sourcesPubMed, EMBASE, Scopus, CINAHL, PsycINFO, Web of Science, CNKI and Wanfang.ResultsOf the 13 167 studies identified, 50 were included (14 qualitative, 34 cross-sectional and 2 cohort). Nearly all quantitative studies examined patient-related non-clinical factors (eg, age) and clinical factors (eg, number of medications) and nine studies examined prescriber-related factors (eg, physician age). A greater number of medications were identified as positively associated with PIPs in 25 quantitative studies, and a higher number of comorbidities, physical comorbidities and psychiatric comorbidities were identified as patient-related clinical risk factors for PIPs. However, other factors showed inconsistent associations with the PIPs. Barriers to medicines optimisation emerged within four analytical themes: prescriber related (eg, inadequate knowledge, concerns of adverse consequences, clinical inertia, lack of communication), patient related (eg, limited understanding, patient non-adherence, drug dependency), environment related (eg, lack of integrated care, insufficient investment, time constraints) and technology related (eg, complexity of implementation and inapplicable guidance). Recommended potential solutions were based on each theme of the barriers identified accordingly (eg, prescriber-related factors: incorporating training courses into continuing medical education).ConclusionsOlder adults with more drugs prescribed and comorbidities may have a greater risk of receiving PIPs in the primary care setting, but it remains unclear whether other factors are related. Barriers to medicines optimisation among primary care older adults comprise multiple factors, and evidence-based and targeted interventions are needed to address these difficulties.PROSPERO registration numberCRD42020216258.
Genomic alterations in biliary tract cancer predict prognosis and immunotherapy outcomes
Authors: Chen Xiaofeng , Wang Deqiang , Liu Jing , Qiu Jingrong , Zhou Jun , Ying Jieer , Shi Yan , Wang Zhaoxia , Lou Haizhou , Cui Jiuwei , Zhang Jingdong , Liu Yunpeng , Zhao Fengjiao , Pan Lanlan , Zhao Jianyi , Zhu Dongqin , Chen Shiqing , Li Xiangcheng , Li Xue , Zhu Liuqing , Shao Yang , Shu Yongqian 
Published: November 2021

BackgroundRecently, immunotherapy with immune checkpoint inhibitors (ICIs) has shown promising efficacy in biliary tract cancer (BTC), which includes gallbladder cancer (GBC) and cholangiocarcinoma (CHOL). Understanding the association between immunotherapy outcomes and the genomic profile of advanced BTC may further improve the clinical benefits from immunotherapy.MethodsGenomic tumor DNA was isolated from 98 Chinese patients with advanced BTC and used for targeted next-generation sequencing of 416 cancer-related genes to identify the genomic alterations common to advanced BTC. Thirty-four patients had received ICI camrelizumab plus gemcitabine and oxaliplatin (from theNCT03486678trial) as a first-line treatment. Tumor-infiltrating immune cells were evaluated using immunofluorescence staining.ResultsKRAS and TP53 mutations were much more frequent in the advanced-stage BTC cohort than in other cohorts with mostly early stage disease. Specifically, KRAS-TP53 co-mutations were favored in advanced CHOL, with a favorable response to immunotherapy, while single KRAS mutations predicted poor prognosis and immunotherapy outcomes for CHOL. Compared with GBC, CHOL had more mutations in genes involved in KRAS signaling; a high mutation load in these genes correlated with poor immunotherapy outcomes and may subsequently cause inferior immunotherapy outcomes for CHOL relative to GBC. Furthermore, a genomic signature including 11 genes was developed; their mutated subtype was associated with poor prognosis and immunotherapy outcomes in both CHOL and GBC. Transcriptome analyses suggested immune dysfunction in the signature mutated subtype, which was validated by tumor microenvironment (TME) evaluation based on detection of immune cell infiltration. Importantly, the signature wild-type subtype with favorable TME may be an advantageous population of immunotherapy.ConclusionsGenomic alterations in advanced BTC were associated with specific prognosis and immunotherapy outcomes. Combining genomic classification with TME evaluation further improved the stratification of immunotherapy outcomes.
Prevalence of systemic lupus erythematosus-related symptoms assessed by using the Connective Tissue Disease Screening Questionnaire in a large population-based cohort
Authors: Lambers Wietske , Arends Suzanne , Roozendaal Caroline , Brouwer Elisabeth , Bootsma Hendrika , Westra Johanna , de Leeuw Karina 
Published: November 2021

BackgroundTo assess the prevalence of self-reported SLE-related symptoms associated with demographic and biochemical data and connective tissue disease (CTD)-related autoantibodies in a large population-based cohort.MethodsParticipants of the Dutch Lifelines population cohort filled out the Connective Tissue Disease Screening Questionnaire (CSQ), including 11 questions focusing on SLE-related symptoms (SLE-CSQ) based on the American College of Rheumatology classification criteria. CTD autoantibody screen was performed in 25% of participants.ResultsOf 85 295 participants with complete SLE-CSQ data, after excluding patients with SLE and other CTDs (n=126), 41 781 (49.1%) had no positively answered questions and 2210 (2.6% of total) had ≥4 positive answers. Participants with ≥4 answers on the SLE-CSQ were significantly younger, more frequently female, had lower body mass index (BMI) and were more often smokers than those with negative scores. Furthermore, counts of leucocytes, neutrophils and monocytes were significantly higher in these participants, while the levels of haemoglobin and creatinine were lower. CTD autoantibodies were present in 2.2% of participants with SLE-CSQ score of 0, compared with 3.5% with SLE-CSQ score ≥4 (p=0.001). Multivariate analysis showed, after adjusting for age, gender, BMI and smoking, that haemoglobin levels remained significantly lower in participants with SLE-CSQ score ≥4.ConclusionsIn this large population-based cohort, 2.6% of participants without diagnosed CTD reported ≥4 positive answers on the SLE-CSQ, indicating high suspicion for SLE. These individuals had demographic and haematological characteristics that differed from the remaining population. Potentially, this questionnaire, in combination with autoantibody determination, can be used as a starting point of a screening cascade in order to detect SLE at an early stage.
Clinically relevant patient clusters identified by machine learning from the clinical development programme of secukinumab in psoriatic arthritis
Authors: Pournara Effie , Kormaksson Matthias , Nash Peter , Ritchlin Christopher T , Kirkham Bruce W , Ligozio Gregory , Pricop Luminita , Ogdie Alexis , Coates Laura C , Schett Georg , McInnes Iain B 
Published: November 2021

ObjectivesIdentify distinct clusters of psoriatic arthritis (PsA) patients based on their baseline articular, entheseal and cutaneous disease manifestations and explore their clinical and therapeutic value.MethodsPooled baseline data in PsA patients (n=1894) treated with secukinumab across four phase 3 studies (FUTURE 2–5) were analysed to determine phenotypes based on clusters of clinical indicators. Finite mixture models methodology was applied to generate clinical clusters and mean longitudinal responses were compared between secukinumab doses (300 vs 150 mg) across identified clusters and clinical indicators through week 52 using machine learning (ML) techniques.ResultsSeven distinct patient clusters were identified. Cluster 1 (very-high (VH) – SWO/TEN (swollen/tender); n=187) was characterised by VH polyarticular burden for both tenderness and swelling of joints, while cluster 2 (H (high) – TEN; n=251) was marked by high polyarticular burden in tender joints and cluster 3 (H – Feet – Dactylitis; n=175) by high burden in joints of feet and dactylitis. For cluster 4 (L (Low) – Nails – Skin; n=209), cluster 5 (L – skin; n=283), cluster 6 (L – Nails; n=294) and cluster 7 (L; n=495) articular burden was low but nail and skin involvement was variable, with cluster 7 marked by mild disease activity across all domains. Greater improvements in the longitudinal responses for enthesitis in cluster 2, enthesitis and Psoriasis Area and Severity Index (PASI) in cluster 4 and PASI in cluster 6 were shown for secukinumab 300 mg compared with 150 mg.ConclusionsPsA clusters identified by ML follow variable response trajectories indicating their potential to predict precise impact on patients’ outcomes.Trial registration numbersNCT01752634, NCT01989468, NCT02294227, NCT02404350
Neutron stars in $$f(\mathtt {R,L_m})$$ gravity with realistic equations of state: joint-constrains with GW170817, massive pulsars, and the PSR J0030+0451 mass-radius from NICER data
Authors: Lobato R. V. , Carvalho G. A. , Bertulani C. A. 
Published: November 2021

AbstractIn this work, we investigate neutron stars (NS) in$$f(\mathtt {R,L_m})$$f(R,Lm)theory of gravity for the case$$f(\mathtt {R,L_m})= \mathtt {R}+ \mathtt {L_m}+ \sigma \mathtt {R}\mathtt {L_m}$$f(R,Lm)=R+Lm+σRLm, where$$\mathtt {R}$$Ris the Ricci scalar and$$\mathtt {L_m}$$Lmthe Lagrangian matter density. In the term$$\sigma \mathtt {R}\mathtt {L_m}$$σRLm,$$\sigma $$σrepresents the coupling between the gravitational and particles fields. For the first time the hydrostatic equilibrium equations in the theory are solved considering realistic equations of state and NS masses and radii obtained are subject to joint constrains from massive pulsars, the gravitational wave event GW170817 and from the PSR J0030+0451 mass-radius from NASA’sNeutron Star Interior Composition Explorer(NICER) data. We show that in this theory of gravity, the mass-radius results can accommodate massive pulsars, while the general theory of relativity can hardly do it. The theory also can explain the observed NS within the radius region constrained by the GW170817 and PSR J0030+0451 observations for masses around$$1.4~M_{\odot }$$1.4M⊙.
Inductive graph invariants and approximation algorithms
Authors: Subramanian C. R. 
Published: November 2021

We introduce and study an inductively defined analogue [Formula: see text] of any increasing graph invariant [Formula: see text]. An invariant [Formula: see text] is increasing if [Formula: see text] whenever [Formula: see text] is an induced subgraph of [Formula: see text]. This inductive analogue simultaneously generalizes and unifies known notions like degeneracy, inductive independence number, etc., into a single generic notion. For any given increasing [Formula: see text], this gets us several new invariants and many of which are also increasing. It is also shown that [Formula: see text] is the minimum (over all orderings) of a value associated with each ordering. We also explore the possibility of computing [Formula: see text] (and a corresponding optimal vertex ordering) and identify some pairs [Formula: see text] for which [Formula: see text] can be computed efficiently for members of [Formula: see text]. In particular, it includes graphs of bounded [Formula: see text] values. Some specific examples (like the class of chordal graphs) have already been studied extensively. We further extend this new notion by (i) allowing vertex weighted graphs, (ii) allowing [Formula: see text] to take values from a totally ordered universe with a minimum and (iii) allowing the consideration of [Formula: see text]-neighborhoods for arbitrary but fixed [Formula: see text]. Such a generalization is employed in designing efficient approximations of some graph optimization problems. Precisely, we obtain efficient algorithms (by generalizing the known algorithm of Ye and Borodin [Y. Ye and A. Borodin, Elimination graphs, ACM Trans. Algorithms 8(2) (2012) 1–23] for special cases) for approximating optimal weighted induced [Formula: see text]-subgraphs and optimal [Formula: see text]-colorings (for hereditary [Formula: see text]’s) within multiplicative factors of (essentially) [Formula: see text] and [Formula: see text] respectively, where [Formula: see text] denotes the inductive analogue (as defined in this work) of optimal size of an unweighted induced [Formula: see text]-subgraph of the input and [Formula: see text] is the minimum size of a forbidden induced subgraph of [Formula: see text]. Our results generalize the previous result on efficiently approximating maximum independent sets and minimum colorings on graphs of bounded inductive independence number to optimal [Formula: see text]-subgraphs and [Formula: see text]-colorings for arbitrary hereditary classes [Formula: see text]. As a corollary, it is also shown that any maximal [Formula: see text]-subgraph approximates an optimal solution within a factor of [Formula: see text] for unweighted graphs, where [Formula: see text] is maximum size of any induced [Formula: see text]-subgraph in any local neighborhood [Formula: see text].
PTP1B Is an Intracellular Checkpoint that Limits T-cell and CAR T-cell Antitumor Immunity
Authors: Wiede Florian , Lu Kun-Hui , Du Xin , Zeissig Mara N. , Xu Rachel , Goh Pei Kee , Xirouchaki Chrysovalantou E. , Hogarth Samuel J. , Greatorex Spencer , Sek Kevin , Daly Roger J. , Beavis Paul A. , Darcy Phillip K. , Tonks Nicholas K. , Tiganis Tony 
Published: November 2021

Abstract

Immunotherapies aimed at alleviating the inhibitory constraints on T cells have revolutionized cancer management. To date, these have focused on the blockade of cell-surface checkpoints such as PD-1. Herein we identify protein tyrosine phosphatase 1B (PTP1B) as an intracellular checkpoint that is upregulated in T cells in tumors. We show that increased PTP1B limits T-cell expansion and cytotoxicity to contribute to tumor growth. T cell–specific PTP1B deletion increased STAT5 signaling, and this enhanced the antigen-induced expansion and cytotoxicity of CD8+ T cells to suppress tumor growth. The pharmacologic inhibition of PTP1B recapitulated the T cell–mediated repression of tumor growth and enhanced the response to PD-1 blockade. Furthermore, the deletion or inhibition of PTP1B enhanced the efficacy of adoptively transferred chimeric antigen receptor (CAR) T cells against solid tumors. Our findings identify PTP1B as an intracellular checkpoint whose inhibition can alleviate the inhibitory constraints on T cells and CAR T cells to combat cancer.

Significance:
Tumors subvert antitumor immunity by engaging checkpoints that promote T-cell exhaustion. Here we identify PTP1B as an intracellular checkpoint and therapeutic target. We show that PTP1B is upregulated in intratumoral T cells and that its deletion or inhibition enhances T-cell antitumor activity and increases CAR T-cell effectiveness against solid tumors.
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In and Out of Control
Authors: Reichenberg Olof 
Published: November 2021

Abstract
The present study aimed to predict job control (i.e., task discretion) based on class and occupation with skill use as a (hypothesized) mechanism in four Western European countries by using the OECD adult skill survey (PIAAC). The countries were Denmark, Belgium, Italy, and the United Kingdom (UK). The study used a Bayesian approach that included multilevel models combined with measurement models. The study uses the international standard classification of occupations with two digits (clustering variable) as well as the European socioeconomic classification (ESeC) measured with three social classes. The results indicate that greater worker technical skills (computer use) and social skills (e.g., negotiate and influence) predict higher levels of job control. Social classes interact with skills to predict job control (except Belgium). Occupational computer skills predict job control (in Belgium and Italy). In conclusion, the study supports predictions by neo-Durkheimians, neo-Weberians, New Structuralists, and relational approaches to inequality.
Taxonomic treatments of Pyrenaria jonquieriana (Theaceae) and related taxa
Authors: YANG YE-KUN , ZHANG QIONG , MA JIN-LIN , YANG SHI-XIONG 
Published: November 2021

On the basis of field investigation and herbarium specimen examination, Tutcheria multisepala, Pyrenaria poilaneana, Parapyrenaria indochinensis and Camellia luuana are treated to the synonymy of Pyrenaria jonquieriana. In addition, lectotypes are designated for the names Pyrenaria jonquieriana and Pyrenaria poilaneana.
Progression of Intracranial Hemorrhage After Chemical Prophylaxis Using Low-Molecular-Weight Heparin in Patients With Traumatic Brain Injury
Authors: Thier Zachary T. , Drake-Lavelle Kelan , Prest Phillip J. , Jones Mark A. , Reeves Jeremy M. , McClung-Smith Catherine F. , Goodwin Tyler M. , Villani Nolan , Metz John , Jackson J. Benjamin 
Published: November 2021

Introduction Chemical prophylaxis using low-molecular-weight heparin (LMWH) is considered a standard of care for venous thromboembolism in trauma patients. Our center performs a head computed tomography (CT) scan 24 hours after initiation with prophylactic LMWH in the setting of a known traumatic brain injury (TBI). The purpose was to determine the overall incidence of ICH progression after chemoprophylaxis in patients with a TBI. Methods This retrospective study was performed at a Level I trauma center, from 1/1/2014 to 12/31/2017. Study patients were drawn from the institution’s trauma registry based on Abbreviated Injury Score codes. Results 778 patients met all inclusion criteria after initial chart review. The proportion of patients with an observed radiographic progression of intracranial hemorrhage after LMWH was 5.8%. 3.1% of patients had a change in clinical management. Observed radiographic progression after LMWH prophylaxis and the presence of SDH on initial CT, the bilateral absence of pupillary response in the emergency department, and a diagnosis of dementia were found to have statistically significant correlation with bleed progression after LMWH was initiated. Conclusion Over a 4-year period, the use of CT to evaluate for radiographic progression of traumatic intracranial hemorrhage 24 hours after receiving LMWH resulted in a change in clinical management for 3.1% of patients. The odds of intracranial hemorrhage progression were approximately 6.5× greater in patients with subdural hemorrhage on initial CT, 3.1× greater in patients with lack of bilateral pupillary response in ED, and 4.2× greater in patients who had been diagnosed with dementia.
A Meta-Analysis of the Effects of Reading Comprehension Interventions on the Reading Comprehension Outcomes of Struggling Readers in Third Through 12th Grades
Authors: Filderman Marissa J. , Austin Christy R. , Boucher Alexis N. , O’Donnell Katherine , Swanson Elizabeth A. 
Published: November 2021

Informed by theories of reading comprehension and prior reviews of reading comprehension intervention, this meta-analysis uniquely contributes to the literature because it describes the relative effects of various approaches to comprehension intervention for struggling readers in Grades 3 through 12. Findings from 64 studies demonstrate significant positive effects of reading comprehension intervention on comprehension outcomes ( g = .59, p < .001, 95% confidence interval [CI] [0.47, 0.74], τ2 = .31). A metaregression model indicated significantly higher effects associated with researcher-developed measures, background knowledge instruction, and strategy instruction, and significantly lower effects associated with instructional enhancements. Grade level, metacognitive approaches, and study quality did not moderate effects. Findings support the use of background knowledge instruction and strategy instruction to support comprehension of struggling readers in upper elementary and beyond.
Implementation of a computer-assisted face-to-face intervention for mapping the social support networks of patients with severe mental illness in routine clinical practice: Analysis of the appropriateness and acceptability of the intervention
Authors: Nicaise Pablo , Garin Hélène , Smith Pierre , d’Oreye de Lantremange Sébastien , Leleux Laurent , Wyngaerden François , Lorant Vincent 
Published: November 2021

Background: Social support is a key dimension of personal recovery for patients with severe mental disorders. Although clinicians and health professionals should monitor the social support resources of patients in order to provide effective treatment, no specific tool or intervention exist for that purpose. Egonet is a computer-assisted intervention for health and social services that enables the mapping, assessment and fostering of patients’ social support networks. Aims: This paper describes the intervention and evaluates the appropriateness and acceptability of its implementation in a clinical setting. Method: We described the computer-assisted intervention. We used a questionnaire to assess how appropriate and acceptable clinicians found a preliminary version to be. We also collected patients’ level of satisfaction with their social support networks before and after the intervention and carried out qualitative interviews. Results: Egonet is made up of four components: (1) a computer-assisted interview for mapping social networks, (2) a remote data server, (3) a data-mining module and (4) a customisable reporting tool. Egonet was implemented for 232 patients by 91 clinicians from five services. The intervention was perceived by clinicians as appropriate and useful for clinical practice, although it was noted that considerable effort was required to obtain its benefits. Patients were slightly more satisfied with their social support after the intervention than before, and expressed the opinion that more attention should be paid to the social support network. Conclusions: EGONET is appropriate and acceptable for use in work related to the social support networks of patients with psychiatric disorders.