bluuebunny/crossref_metadata_2025_split huggingface dataset:
Envelope Method for Time- and Space-Dependent Reliability Prediction
Authors: Wu Hao , Du Xiaoping 
Published: March 2022

Abstract
Reliability can be predicted by a limit-state function, which may vary with time and space. This work extends the envelope method for a time-dependent limit-state function to a time- and space-dependent limit-state function. The proposed method uses the envelope function of time- and space-dependent limit-state function. It at first searches for the most probable point (MPP) of the envelope function using the sequential efficient global optimization in the domain of the space and time under consideration. Then the envelope function is approximated by a quadratic function at the MPP for which analytic gradient and Hessian matrix of the envelope function are derived. Subsequently, the second-order saddlepoint approximation method is employed to estimate the probability of failure. Three examples demonstrate the effectiveness of the proposed method. The method can efficiently produce an accurate reliability prediction when the MPP is within the domain of the space and time under consideration.
Validation and adaptation of the Charlson Comorbidity Index using administrative data from the Colombian health system: retrospective cohort study
Authors: Oliveros Henry , Buitrago Giancarlo 
Published: March 2022

ObjectiveTo validate the Charlson Comorbidity Index (CCI) for the Colombian population using administrative databases from the health insurance system.DesignRetrospective cohort study.SettingDatabase reports of events related to services that insurers provided (Health Promoter Enterprises, EPS in Spanish) in the Colombian health system, which covered 22.19 million residents in 2016.ParticipantsThe study cohort comprised 3 849 849 patients aged 18 years and up admitted to the Colombian hospitals between 1 January and 31 December 2016.Primary outcomeThe study aimed to gauge the CCI’s predictive value for mortality by comparing the calibration and discrimination of three different versions of the index, with mortality information obtained from death certificates, including date of death and diagnoses associated with cause of death. Follow-up was conducted for at least 1 year.ResultsAltogether, 46 429 patients died within 1 year (1.21%). Discriminatory power in predicting 1-year mortality was calculated for three versions of the ICC. In the original CCI model, the area under the Receiver operating characteristic (ROC) curve was 0.906 (95% CI (0.906 to 0.907), p<0.001). In the version for Colombia, it was 0.908 (95% CI (0.908 to 0.909), p<0.001) and for the new model it was 0.909 (95% CI (0.908 to 0.910), p<0.001).ConclusionsAdapting the CCI based on the 14 predictive variables of the new model resulted in an adequate predictive value for 1-year mortality in patients who were hospitalised for all causes. These findings support the use of the modified CCI in the Colombian population.
Does a screening checklist for complex health and social care needs have potential clinical usefulness for predicting unplanned hospital readmissions in intensive care survivors: development and prospective cohort study
Authors: Walsh Timothy Simon , Pauley Ellen , Donaghy Eddie , Thompson Joanne , Barclay Lucy , Parker Richard Anthony , Weir Christopher , Marple James 
Published: March 2022

ObjectivesIntensive care (ICU) survivors are at high risk of long-term physical and psychosocial problems. Unplanned hospital readmission rates are high, but the best way to triage patients for interventions is uncertain. We aimed to develop and evaluate a screening checklist to help predict subsequent readmissions or deaths.DesignA checklist for complex health and social care needs (CHSCNs) was developed based on previous research, comprising six items: multimorbidity; polypharmacy; frequent previous hospitalisations; mental health issues; fragile social circumstances and impaired activities of daily living. Patients were considered to have CHSCNs if two or more were present. We prospectively screened all ICU discharges for CHSCNs for 12 months.SettingICU, Royal Infirmary, Edinburgh, UK.ParticipantsICU survivors over a 12-month period (1 June 2018 and 31 May 2019).InterventionsNone.Outcome measureReadmission or death in the community within 3 months postindex hospital discharge.ResultsOf 1174 ICU survivors, 937 were discharged alive from the hospital. Of these 253 (27%) were classified as having CHSCNs. In total 28% (266/937) patients were readmitted (N=238) or died (N=28) within 3 months. Among CHSCNs patients 45% (n=115) patients were readmitted (N=105) or died (N=10). Patients without CHSCNs had a 22% readmission (N=133) or death (N=18) rate. The checklist had: sensitivity 43% (95% CI 37% to 49%), specificity 79% (95% CI 76% to 82%), positive predictive value 45% (95% CI 41% to 51%), and negative predictive value 78% (95% CI 76% to 80%). Relative risk of readmission/death for patients with CHSCNs was 2.06 (95% CI 1.69 to 2.50), indicating a pretest to post-test probability change of 28%–45%. The checklist demonstrated high inter-rater reliability (percentage agreement ≥87% for all domains; overall kappa, 0.84).ConclusionsEarly evaluation of a screening checklist for CHSCNs at ICU discharge suggests potential clinical usefulness, but this requires further evaluation as part of a care pathway.
Cochlear implant aesthetics and its impact on stigma, social interaction and quality of life: a mixed-methods study protocol
Authors: Rapport Frances , Lo Chi Yhun , Elks Beth , Warren Chris , Clay-Williams Robyn 
Published: March 2022

IntroductionAwareness of the benefits of cochlear implants is low, and barriers such as fear of surgery and ongoing rehabilitation have been noted. Perceived stigma associated with hearing loss also plays a key role, with many adults not wanting to appear old or be identified as a person with a disability. In effect, a cochlear implant makes deafness visible. New technologies have led to a smaller external profile for some types of cochlear implants, but qualitative assessments of benefit have not been explored. This study will examine cochlear implant aesthetics and cosmetics, and its impact on perceived stigma, social interactions, communication and quality of life. A particular focus will be the examination of totally implantable device concepts. A secondary aim is to understand what research techniques are best suited and most appealing for cochlear implant recipients, to assist in future study design and data collection methods.Methods and analysisThis study utilises a mixed-methods design. Three datasets will be collected from each participant with an expected sample size of 10–15 participants to allow for data saturation of themes elicited. Each participant will complete a demographic questionnaire, a quickfire survey (a short concise questionnaire on a topic of research familiarity and preference) and a semi-structured interview. Questionnaire and quickfire survey data will be analysed using descriptive statistics. Interviews will be transcribed and analysed thematically. All participants will be adults with more than 1 year of experience using cochlear implants.Ethics and disseminationThis study has been granted ethical approval from Macquarie University (HREC: 520211056232432) and meets the requirements set out in the National Statement on Ethical Conduct in Human Research. Study findings will be disseminated widely through international peer-reviewed journal articles, public and academic presentations, plain language summaries for participants and an executive summary for the project funder. This work was supported by Cochlear Limited (Cochlear Ltd). The funder will have no role in conducting or reporting on the study.
Targeted systemic therapies for psoriatic arthritis: a systematic review and comparative synthesis of short-term articular, dermatological, enthesitis and dactylitis outcomes
Authors: McInnes Iain B , Sawyer Laura M , Markus Kristen , LeReun Corinne , Sabry-Grant Celia , Helliwell Philip S 
Published: March 2022

IntroductionRandomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis (PsA); few have compared them head to head.ObjectivesTo compare the efficacy and safety of all evaluated DMARDs for active PsA, with a special focus on biological DMARDs (bDMARDs) licensed for PsA or psoriasis.MethodsA systematic review identified RCTs and Bayesian network meta-analysis (NMA) compared treatments on efficacy (American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, resolution of enthesitis and dactylitis) and safety (patients discontinuing due to adverse events (DAE)) outcomes. Subgroup analyses explored ACR response among patients with and without prior biological therapy exposure.ResultsThe NMA included 46 studies. Results indicate that some tumour necrosis factor inhibitors (anti-TNFs) may perform numerically, but not significantly, better than interleukin (IL) inhibitors on ACR response but perform worse on PASI response. Few significant differences between bDMARDs on ACR response were observed after subgrouping for prior bDMARD exposure. Guselkumab and IL-17A or IL-17RA inhibitors—brodalumab, ixekizumab, secukinumab—were best on PASI response. These IL-inhibitors and adalimumab were similarly efficacious on resolution of enthesitis and dactylitis. Infliximab with and without methotrexate, certolizumab 400 mg every 4 weeks and tildrakizumab showed the highest rates of DAE; abatacept, golimumab and the IL-inhibitors, the lowest.ConclusionsDespite similar efficacy for ACR response, IL-17A and IL-17RA inhibitors and guselkumab offered preferential efficacy to anti-TNFs in skin manifestations, and for enthesitis and dactylitis, thereby supporting drug selection based on predominant clinical phenotype.
Atmospheric ammonia causes histopathological lesions, cell cycle blockage, and apoptosis of spleen in chickens
Authors: Chen Lin , Cai Tong , Zhao Cuiyan , Bai Shiping , Shu Gang , Wen Changlin , Xu Qinkun , Peng Xi 
Published: March 2022

This experiment was conducted to investigate the effect of atmospheric ammonia (NH3) on histological changes, cell cycle distribution, and apoptosis of the spleen in chickens. Two hundred forty chickens were randomly allocated to the control group (without NH3 challenge) and NH3 group (70 ± 5 ppm NH3). The experiment lasted for 8 days. The results showed that NH3 exposure caused decreased relative weight ( P < 0.05), dysplasia of white pulps, obvious ultrastructural lesions, upregulation of G0G1 phase cells, excessive apoptosis, and oxidative stress ( P < 0.05) in the spleen. The mechanisms of cell cycle blockage were closely related to the upregulation of the P53 and P21 genes ( P < 0.05), the downregulation of the cyclin D1 and CDK6 genes ( P < 0.05), and the decrease of proliferating cell nuclear antigen (PCNA) protein ( P < 0.05). The activated apoptosis resulted from the increased gene and protein expression of Bax and caspase-3 ( P < 0.05), and the decreased gene and protein expression of Bcl-2 ( P < 0.05). The results suggested that 70 ± 5 ppm NH3 caused the spleen dysplasia, which was closely related to the cell cycle arrest and mitochondrial apoptotic pathway activation.
Association between Sarcopenia and Insulin-Like Growth Factor-1, Myostatin, and Insulin Resistance in Elderly Patients Undergoing Hemodialysis
Authors: Widajanti Novira , Soelistijo SoebagijoAdi , Hadi Usman , Thaha Mochammad , Aditiawardana  , Widodo  , Firdausi Hadiq , Nurina YafanitaIzzati , Asikin MiraDelima , Srinowati Hersih , Syakdiyah NoerHalimatus 
Published: March 2022

Sarcopenia is common in hemodialysis patients, especially in the elderly patients undergoing hemodialysis. Various factors may contribute to the occurrence of sarcopenia, such as anabolic and catabolic imbalance. This study aims to investigate the correlation of insulin-like growth factor-1 (IGF-1) levels as an anabolic factor, myostatin levels, and insulin resistance as catabolic factors with sarcopenia in the pathogenesis of sarcopenia in elderly patients undergoing hemodialysis. A total of 40 subjects aged 60 years or more who undergoing hemodialysis in Dr. Soetomo Hospital Surabaya were included in this cross-sectional study. Sarcopenia was diagnosed according to Asian Working Group Sarcopenia 2019 criteria. IGF-1, myostatin, and insulin resistance levels were measured once before hemodialysis. Subjects with sarcopenia diagnosis were 33 (82.5%), that is, 19 (47.5%) men and 14 (35%) women. There were 28 (70%) of the subjects diagnosed with severe sarcopenia. Furthermore, there were significant differences in the characteristics and geriatric parameters between the sarcopenia and nonsarcopenia groups. There were differences between the two groups in hemoglobin levels, IGF-1 levels, myostatin levels, homeostasis model assessment-insulin resistance (HOMA-IR) levels, muscle mass, handgrip strength, body mass index status, mini nutritional assessment status, and physical activity scale for elderly status (all

p

< 0.05). Correlation analyses showed that IGF-1 levels negatively correlated with sarcopenia status in elderly patients undergoing hemodialysis (

p

< 0.05). On the contrary, myostatin and HOMA-IR levels were positively correlated with sarcopenia status in elderly patients undergoing hemodialysis (all

p

< 0.05). Based on this recent study, IGF-1, myostatin, and insulin resistance were significantly correlated with sarcopenia in elderly patients undergoing hemodialysis.
Clinical Effect of Qili Qiangxin Capsule Combined with Sacubitril-Valsartan in Patients with Chronic Heart Failure
Authors: Yao Jiafang , Liu Dan 
Published: March 2022

The clinical effect of Qili Qiangxin capsule combined with sacubitril-valsartan on patients with chronic heart failure was studied. We selected 108 patients with chronic heart failure in our hospital from March 2016 to January 2020 and divided them into a control group and a study group according to the random table method, with 54 cases in each. The control group took sacubitril and valsartan orally, and the study group took Qili Qiangxin pill on the basis of sacubitril and valsartan. The course of the treatment for 2 groups is 4 weeks. We compared the total effective rate of the treatment of the 2 groups for 4 weeks, cardiac function (left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF)) before and after 4 weeks of treatment, 6 min walking distance (6MWT), changes in cTnI and NT-proBNP levels, and adverse reactions. The total effective rate in the study group (90.74%) is higher than that in the control group (72.22%) (

P

＜0.05). After 4 weeks of treatment, the study group LVESV (45.23 ± 2.98 mm) and LVEDV (43.38 ± 4.01 mm) are lower than those of the control group ((49.98 ± 2.56 mm) and (50.75 ± 3.49 mm), respectively), while LVEF (47.38 ± 2.78%) is higher than that in the control group (42.08 ± 3.24%) (

P

＜ 0.05). After 4 weeks of treatment, the study group 6MWT (476.58 ± 31.25 m) of patients with chronic heart failure is higher than that of the control group (396.52 ± 24.52 m) (P ＜0.05). After 4 weeks of treatment, the study group serum cTnI (0.36 ± 0.12 μg/L) and NT-proBNP (276.91 ± 30.12 pg/ml) of patients with chronic heart failure are lower than those in the control group (0.87 ± 0.25 μg/L) and (367.48 ± 48.57 pg/ml) (

P

＜0.05). There is no significant difference between the adverse reactions in the two groups (

P

＞ 0.05). Conclusion: Xinbao pills combined with sacubitril and valsartan have a good effect on patients with chronic heart failure, which can improve the heart function and exercise endurance and reduce serum cTnI and NT-proBNP levels.
Cross-Site Concordance Evaluation of Tumor DNA and RNA Sequencing Platforms for the CIMAC-CIDC Network
Authors: Zeng Zexian , Fu Jingxin , Cibulskis Carrie , Jhaveri Aashna , Gumbs Curtis , Das Biswajit , Sanchez-Espiridion Beatriz , Janssens Sylvie , Taing Len , Wang Jin , Lindsay James , Vilimas Tomas , Zhang Jianhua , Tokheim Collin , Sahu Avinash , Jiang Peng , Yan Chunhua , Duose Dzifa Yawa , Cerami Ethan , Chen Li , Cohen David , Chen Qingrong , Enos Rebecca , Huang Xin , Lee Jack J. , Liu Yang , Neuberg Donna S. , Nguyen Cu , Patterson Candace , Sarkar Sharmistha , Shukla Sachet , Tang Ming , Tsuji Junko , Uduman Mohamed , Wang Xiaoman , Weirather Jason L. , Yu Jijun , Yu Joyce , Zhang Jianjun , Zhang Jiexin , Meerzaman Daoud , Thurin Magdalena , Futreal Andrew , Karlovich Chris , Gabriel Stacey B. , Wistuba Ignacio Ivan , Liu X. Shirley , Wu Catherine J. 
Published: March 2022

Abstract

Purpose:
Whole-exome (WES) and RNA sequencing (RNA-seq) are key components of cancer immunogenomic analyses. To evaluate the consistency of tumor WES and RNA-seq profiling platforms across different centers, the Cancer Immune Monitoring and Analysis Centers (CIMAC) and the Cancer Immunologic Data Commons (CIDC) conducted a systematic harmonization study.

Experimental Design:
DNA and RNA were centrally extracted from fresh frozen and formalin-fixed paraffin-embedded non–small cell lung carcinoma tumors and distributed to three centers for WES and RNA-seq profiling. In addition, two 10-plex HapMap cell line pools with known mutations were used to evaluate the accuracy of the WES platforms.

Results:
The WES platforms achieved high precision (&gt; 0.98) and recall (&gt; 0.87) on the HapMap pools when evaluated on loci using &gt; 50× common coverage. Nonsynonymous mutations clustered by tumor sample, achieving an index of specific agreement above 0.67 among replicates, centers, and sample processing. A DV200 &gt; 24% for RNA, as a putative presequencing RNA quality control (QC) metric, was found to be a reliable threshold for generating consistent expression readouts in RNA-seq and NanoString data. MedTIN &gt; 30 was likewise assessed as a reliable RNA-seq QC metric, above which samples from the same tumor across replicates, centers, and sample processing runs could be robustly clustered and HLA typing, immune infiltration, and immune repertoire inference could be performed.

Conclusions:
The CIMAC collaborating laboratory platforms effectively generated consistent WES and RNA-seq data and enable robust cross-trial comparisons and meta-analyses of highly complex immuno-oncology biomarker data across the NCI CIMAC-CIDC Network.
Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors
Authors: Vesely Clare , Wong Yien Ning Sophia , Childs Alexa , Akarca Ayse U. , Dhami Pawan , Vaikkinen Heli , Conde Lucia , Herrero Javier , Ogunbiyi Olagunju , Gander Amir , Luong Tu Vinh , Thirlwell Chrissie , Caplin Martyn , Toumpanakis Christos , Peggs Karl , Quezada Sergio A. , Marafioti Teresa , Meyer Tim 
Published: March 2022

Abstract

Purpose:
The immune tumor microenvironment and the potential therapeutic opportunities for immunotherapy in small intestinal neuroendocrine tumors (siNET) have not been fully defined.

Experimental Design:
Herein, we studied 40 patients with primary and synchronous metastatic siNETs, and matched blood and normal tissue obtained during surgery. We interrogated the immune checkpoint landscape using multi-parametric flow cytometry. In addition, matched FFPE tissue was obtained for multi-parametric IHC to determine the relative abundance and distribution of T-cell infiltrate. Tumor mutational burden (TMB) was also assessed and correlated with immune infiltration.

Results:
Effector tumor-infiltrating lymphocytes (TIL) had a higher expression of PD-1 in the tumor microenvironment compared with the periphery. In addition, CD8+ TILs had a significantly higher co-expression of PD-1/ICOS and PD-1/CTLA-4 (cytotoxic T lymphocyte antigen-4) and higher levels of PD-1 expression compared with normal tissue. IHC revealed that the majority of cases have ≤10% intra-tumoral T cells but a higher number of peri-tumoral T cells, demonstrating an “exclusion” phenotype. Finally, we confirmed that siNETs have a low TMB compared with other tumor types in the TCGA database but did not find a correlation between TMB and CD8/Treg ratio.

Conclusions:
Taken together, these results suggest that a combination therapy approach will be required to enhance the immune response, using PD-1 as a checkpoint immunomodulator backbone in combination with other checkpoint targeting molecules (CTLA-4 or ICOS), or with drugs targeting other pathways to recruit “excluded” T cells into the tumor microenvironment to treat patients with siNETs.
One Size Does Not Fit All: Breast Cancer in Young Women
Authors: Yehia Lamis , Eng Charis 
Published: March 2022

SummaryBreast cancers occurring in young women remain poorly characterized. Through studying a series of very young women with breast cancer compared with older women with breast cancer, distinct biological features were identified, with important implications for the personalized genomics-driven management of these cancers.See related article by Waks et al., p. 2339
The Role of ARID1A in the Nonestrogenic Modulation of IGF-1 Signaling
Authors: Jdeed Sham , Erdős Edina , Bálint Bálint L. , Uray Iván P. 
Published: March 2022

Abstract

Gaining pharmacologic access to the potential of ARID1A, a tumor suppressor protein, to mediate transcriptional control over cancer gene expression is an unresolved challenge. Retinoid X receptor ligands are pleiotropic, incompletely understood tools that regulate breast epithelial cell proliferation and differentiation. We found that low-dose bexarotene (Bex) combined with the nonselective beta-blocker carvedilol (Carv) reduces proliferation of MCF10DCIS.com cells and markedly suppresses ARID1A levels. Similarly, Carv synergized with Bex in MCF-7 cells to suppress cell growth. Chromatin immunoprecipitation sequencing analysis revealed that under nonestrogenic conditions Bex + Carv alters the concerted genomic distribution of the chromatin remodeler ARID1A and acetylated histone H3K27, at sites related to insulin-like growth factor (IGF) signaling. Several distinct sites of ARID1A enrichment were identified in the IGF-1 receptor and IRS1 genes, associated with a suppression of both proteins. The knock-down of ARID1A increased IGF-1R levels, prevented IGF-1R and IRS1 suppression upon Bex + Carv, and stimulated proliferation. In vitro IGF-1 receptor neutralizing antibody suppressed cell growth, while elevated IGF-1R or IRS1 expression was associated with poor survival of patients with ER-negative breast cancer. Our study demonstrates direct impact of ARID1A redistribution on the expression and growth regulation of IGF-1–related genes, induced by repurposed clinical drugs under nonestrogenic conditions.

Implications:
This study underscores the possibility of the pharmacologic modulation of the ARID1A factor to downregulate protumorigenic IGF-1 activity in patients with postmenopausal breast cancer undergoing aromatase inhibitor treatment.