bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 lung injury as a primer for immune checkpoint inhibitors (ICIs)-related pneumonia in a patient affected by squamous head and neck carcinoma treated with PD-L1 blockade: a case report
Authors: Dipasquale Angelo , Persico Pasquale , Lorenzi Elena , Rahal Daoud , Santoro Armando , Simonelli Matteo 
Published: February 2021

By the beginning of the global pandemic, SARS-CoV-2 infection has dramatically impacted on oncology daily practice. In the current oncological landscape, where immunotherapy has revolutionized the treatment of several malignancies, distinguishing between COVID-19 and immune-mediated pneumonitis can be hard because of shared clinical, radiological and pathological features. Indeed, their common mechanism of aberrant inflammation could lead to a mutual and amplifying interaction.We describe the case of a 65–year-old patient affected by metastatic squamous head and neck cancer and candidate to an experimental therapy including an anti-PD-L1 agent. COVID-19 ground-glass opacities under resolution were an incidental finding during screening procedures and worsened after starting immunotherapy. The diagnostic work-up was consistent with ICIs-related pneumonia and it is conceivable that lung injury by SARS-CoV-2 has acted as an inflammatory primer for the development of the immune-related adverse event.Patients recovered from COVID-19 starting ICIs could be at greater risk of recall immune-mediated pneumonitis. Nasopharyngeal swab and chest CT scan are recommended before starting immunotherapy. The awareness of the phenomenon could allow an easier interpretation of radiological changes under treatment and a faster diagnostic work-up to resume ICIs. In the presence of clinical benefit, for asymptomatic ICIs-related pneumonia a watchful-waiting approach and immunotherapy prosecution are suggested.
Executive dysfunction and risk of suicide in older adults: a population-based prospective cohort study
Authors: Oh Dae Jong , Han Ji Won , Bae Jong Bin , Kim Tae Hui , Kwak Kyung Phil , Kim Bong Jo , Kim Shin Gyeom , Kim Jeong Lan , Moon Seok Woo , Park Joon Hyuk , Ryu Seung-Ho , Youn Jong Chul , Lee Dong Young , Lee Dong Woo , Lee Seok Bum , Lee Jung Jae , Jhoo Jin Hyeong , Kim Ki Woong 
Published: February 2021

ObjectiveIt is uncertain what factors increases the risk of suicide in older adults without depression, and it is unknown whether executive dysfunction (ED) is one of those factors. We aimed to examine the effect of ED on the risk of suicide in non-demented older adults without depression.MethodsIn an ongoing population-based prospective cohort of Korean older adults, we identified suicide using the National Mortality Database and suicidal ideation or attempt (SIA) based on the Korean version of the Mini International Neuropsychiatric Interview. We defined ED as performing below −1.5 SD of age-adjusted, gender-adjusted and education-adjusted norms in any of following tests: Frontal Assessment Battery, Trail Making Test A, Digit Span Test or Verbal Fluency Test.ResultsThe mean age of the 4791 participants at baseline was 69.7 (SD 6.4) years, and 57.1% of them were women (mean follow-up duration=4.9 years). ED at baseline increased the risk of suicide by about seven times (HR 7.20, 95% CI 1.84 to 28.12, p=0.005) but did not change the risk of SIA. However, cognitive impairment without ED did not change the risks of suicide and SIA. In participants with ED, being aged 75 years or above, living alone, and having a low socioeconomic status were associated with the risk of suicide.ConclusionED is a strong risk factor of late life suicide independent from depression, particularly in very old adults living in disadvantaged environments.
A novel rabbit thromboembolic occlusion model
Authors: Ding Yong-Hong , Fitzgerald Seán , Liu Yang , Dai Daying , Jakaitis Daniel , Doyle Karen , Brinjikji Waleed , Kallmes David F , Savastano Luis , Kadirvel Ramanathan 
Published: February 2021

BackgroundTo develop a preclinical thromboembolic occlusion model for studying revascularization strategies.MethodsClot analog with barium sulfate was injected into the distal aorta in 9 New Zealand white rabbits. The situation of aorta occlusion was compared among fibrin-rich (n=4), red blood cell (RBC)-rich (n=3), and whole blood clot analogs (n=2) using digital subtraction angiography. Arterial geometries, histologic features and circumferential stretch of the distal aorta in rabbits were compared with the common carotid artery in swine and the distal internal carotid artery (ICA) in humans. Aspiration thrombectomy and mechanical thrombectomy using a stent retriever were performed in two rabbits.ResultsThe aortic bifurcation was occluded after a single delivery of clot in 4 cases. It was occluded after the second clot injection in the 5 remaining rabbits. Fragmentation of RBC-rich clots occurred during clot injection in 2 cases. The mean diameters of the distal aorta and right common iliac artery in rabbits were 3.7±0.4 and 2.8±0.3 mm, respectively; the mean diameters of human ICA, and first and second segments of the middle cerebral artery (M1, M2) were 3.6±0.4, 3.1±0.4, and 2.4±0.4 mm, respectively. Arterial revascularization was achieved in both rabbits. Geometric, mechanical and histological factors of the distal aorta in rabbit were more close to human distal ICA than swine carotid artery.ConclusionArterial occlusion can be achieved at the aortic bifurcation in rabbits, which is comparable to human ICA bifurcation. This thrombectomy model has the potential to be used for testing of thrombectomy devices.
Associations between left bundle branch block with different PR intervals, QRS durations, heart rates and the risk of heart failure: a register-based cohort study using ECG data from the primary care setting
Authors: Søndergaard Marc Meller , Riis Johannes , Bodker Karoline Willum , Hansen Steen Møller , Nielsen Jesper , Graff Claus , Pietersen Adrian Holger , Nielsen Jonas Bille , Tayal Bhupendar , Polcwiartek Christoffer , Torp-Pedersen Christian , Soegaard Peter , Kragholm Kristian Hay 
Published: February 2021

AimLeft bundle branch block (LBBB) is associated with an increased risk of heart failure (HF). We assessed the impact of common ECG parameters on this association using large-scale data.Methods and resultsUsing ECGs recorded in a large primary care population from 2001 to 2011, we identified HF-naive patients with a first-time LBBB ECG. We obtained information on sex, age, emigration, medication, diseases and death from Danish registries. We investigated the association between the PR interval, QRS duration, and heart rate and the risk of HF over a 2-year follow-up period using Cox regression analysis.Of 2471 included patients with LBBB, 464 (18.8%) developed HF during follow-up. A significant interaction was found between QRS duration and heart rate (p<0.01), and the analyses were stratified on these parameters. Using a QRS duration <150 ms and a heart rate <70 beats per minute (bpm) as the reference, all groups were statistically significantly associated with the development of HF. Patients with a QRS duration ≥150 ms and heart rate ≥70 bpm had the highest risk of developing HF (HR 3.17 (95% CI 2.41 to 4.18, p<0.001). There was no association between the PR interval and HF after adjustment.ConclusionProlonged QRS duration and higher heart rate were associated with increased risk of HF among primary care patients with LBBB, while no association was observed with PR interval. Patients with LBBB with both a prolonged QRS duration (≥150 ms) and higher heart rate (≥70 bpm) have the highest risk of developing HF.
Reprogramming Transcription Factors Oct4 and Sox2 Induce a BRD-Dependent Immunosuppressive Transcriptome in GBM-Propagating Cells
Authors: Ma Tengjiao , Hu Chengchen , Lal Bachchu , Zhou Weiqiang , Ma Yongxin , Ying Mingyao , Prinos Panagiotis , Quiñones-Hinojosa Alfredo , Lim Michael , Laterra John , Li Yunqing 
Published: February 2021

Abstract

A subset of stem-like cells in glioblastoma (GBM; GSC) underlies tumor propagation, therapeutic resistance, and tumor recurrence. Immune evasion is critical for GSCs to carry out these functions. However, the molecular mechanisms employed by GSCs to escape antitumor immunity remain largely unknown. The reprogramming transcription factors Oct4 and Sox2 function as core multipotency factors and play an essential role in the formation and maintenance of GSCs, but the roles of these transcription factors in GSC immune escape have not been well explored. Here we examine how Oct4/Sox2 coexpression contributes to the immunosuppressive phenotype of GSCs. Combined transcription profiling and functional studies of Oct4/Sox2 coexpressing GSCs and differentiated GBM cells demonstrated that Oct4 and Sox2 cooperatively induce an immunosuppressive transcriptome consisting of multiple immunosuppressive checkpoints (i.e., PD-L1, CD70, A2aR, TDO) and dysregulation of cytokines and chemokines that are associated with an immunosuppressive tumor microenvironment. Mechanistically, induction and function of BRD/H3k27Ac-dependent immunosuppressive genes played a role in the immunosuppressive phenotype of GSCs. Pan-BET bromodomain inhibitors (e.g., JQ1) and shBRD4 constructs significantly inhibited the immunosuppressive transcriptome and immunosuppressive biological responses induced by Oct4/Sox2. Our findings identify targetable mechanisms by which tumor-propagating GSCs contribute to the immunosuppressive microenvironment in GBM.

Significance:
This report identifies mechanisms by which the reprogramming transcription factors Oct4 and Sox2 function to drive the immunomodulatory transcriptome of GSCs and contribute to the immunosuppressive microenvironment in GBM.
Prospective Identification of Elevated Circulating CDCP1 in Patients Years before Onset of Lung Cancer
Authors: Dagnino Sonia , Bodinier Barbara , Guida Florence , Smith-Byrne Karl , Petrovic Dusan , Whitaker Matthew D. , Haugdahl Nøst Therese , Agnoli Claudia , Palli Domenico , Sacerdote Carlotta , Panico Salvatore , Tumino Rosario , Schulze Matthias B. , Johansson Mikael , Keski-Rahkonen Pekka , Scalbert Augustin , Vineis Paolo , Johansson Mattias , Sandanger Torkjel M. , Vermeulen Roel C.H. , Chadeau-Hyam Marc 
Published: February 2021

Abstract

Increasing evidence points to a role for inflammation in lung carcinogenesis. A small number of circulating inflammatory proteins have been identified as showing elevated levels prior to lung cancer diagnosis, indicating the potential for prospective circulating protein concentration as a marker of early carcinogenesis. To identify novel markers of lung cancer risk, we measured a panel of 92 circulating inflammatory proteins in 648 prediagnostic blood samples from two prospective cohorts in Italy and Norway (women only). To preserve the comparability of results and protect against confounding factors, the main statistical analyses were conducted in women from both studies, with replication sought in men (Italian participants). Univariate and penalized regression models revealed for the first time higher blood levels of CDCP1 protein in cases that went on to develop lung cancer compared with controls, irrespective of time to diagnosis, smoking habits, and gender. This association was validated in an additional 450 samples. Associations were stronger for future cases of adenocarcinoma where CDCP1 showed better explanatory performance. Integrative analyses combining gene expression and protein levels of CDCP1 measured in the same individuals suggested a link between CDCP1 and the expression of transcripts of LRRN3 and SEM1. Enrichment analyses indicated a potential role for CDCP1 in pathways related to cell adhesion and mobility, such as the WNT/β-catenin pathway. Overall, this study identifies lung cancer–related dysregulation of CDCP1 expression years before diagnosis.

Significance:
Prospective proteomics analyses reveal an association between increased levels of circulating CDCP1 and lung carcinogenesis irrespective of smoking and years before diagnosis, and integrating gene expression indicates potential underlying mechanisms.
See related commentary by Itzstein et al., p. 3441.
A Randomized Phase II Study of Coexpression Extrapolation (COXEN) with Neoadjuvant Chemotherapy for Bladder Cancer (SWOG S1314; NCT02177695)
Authors: Flaig Thomas W. , Tangen Catherine M. , Daneshmand Siamak , Alva Ajjai , Lerner Seth P. , Lucia M. Scott , McConkey David J. , Theodorescu Dan , Goldkorn Amir , Milowsky Matthew I. , Bangs Rick , MacVicar Gary R. , Bastos Bruno R. , Fowles Jared S. , Gustafson Daniel L. , Plets Melissa , Thompson Ian M. 
Published: February 2021

Abstract

Purpose:
Dose-dense methotrexate-vinblastine-adriamycin-cisplatin (ddMVAC) and gemcitabine-cisplatin (GC) are accepted neoadjuvant regimens for muscle-invasive bladder cancer. The aim of this study was to validate the score from a coexpression extrapolation (COXEN) algorithm–generated gene expression model (GEM) as a biomarker in patients undergoing radical cystectomy.

Patients and Methods:
Eligibility included cT2-T4a N0 M0, urothelial bladder cancer, ≥ 5 mm of viable tumor, cisplatin eligible, with plan for cystectomy; 237 patients were randomized between ddMVAC, given every 14 days for four cycles, and GC, given every 21 days for four cycles. The primary objective assessed prespecified dichotomous treatment-specific COXEN score as predictive of pT0 rate or ≤ pT1 (downstaging) at surgery.

Results:
Among 167 evaluable patients, the OR for pT0 with the GC GEM score in GC-treated patients was 2.63 [P = 0.10; 95% confidence interval (CI), 0.82–8.36]; for the ddMVAC COXEN GEM score with ddMVAC treatment, the OR was 1.12 (P = 0.82, 95% CI, 0.42–2.95). The GC GEM score was applied to pooled arms (GC and ddMVAC) for downstaging with an OR of 2.33 (P = 0.02; 95% CI, 1.11–4.89). In an intention-to-treat analysis of eligible patients (n = 227), pT0 rates for ddMVAC and GC were 28% and 30% (P = 0.75); downstaging was 47% and 40% (P = 0.27), respectively.

Conclusions:
Treatment-specific COXEN scores were not significantly predictive for response to individual chemotherapy treatment. The COXEN GEM GC score was significantly associated with downstaging in the pooled arms. Additional biomarker development is planned.
Dynamic Analysis Of Two Link Robot Manipulator For Control Design Using PID Computed Torque Control.
Authors: Shah Jolly Atit , Rattan S S 
Published: February 2021

<p>Due to their advantage of high speed, accuracy and repeatability, robot manipulators have become major component of manufacturing industries and even now a days they become part of routine life. </p><p>Two link robot manipulator is a very basic classical and simple example of robot followed in understanding of basic fundamentals of robotic manipulator. The equation of motion for two link robot is a nonlinear differential equation. For higher degrees of freedom, as the closed form solutions are very difficult we have to use numerical solution. Here we focused mainly on control of robot manipulator to get the desired position using combination of two classical methods PID and computed torque control method after deriving the equation of motion. For the same simulation is represented using MATLAB and compared with computed torque control method.</p>
Systematic Review and Meta-Analysis of Interventions to Slow Progression of Abdominal Aortic Aneurysm in Mouse Models
Authors: Phie James , Thanigaimani Shivshankar , Golledge Jonathan 
Published: February 2021

Objective:
There are no current effective abdominal aortic aneurysm (AAA) drug therapies. An important limitation of most preclinical studies is that they test the effect of drugs on AAA formation rather than AAA progression. The aim of this study was to systematically review AAA mouse model studies that have tested the effect of interventions in limiting the progression of preestablished AAA.

Approach and Results:

The literature search identified 35 studies meeting eligibility, and 30 (n=935 mice) contributed to the meta-analyses. AAAs were induced with angiotensin II (n=745 mice), calcium chloride (n=91 mice), or elastase (n=99 mice). Anti-inflammatory drugs (standardized mean difference [SMD], 1.62 [95% CI, 0.93–2.30]), protease inhibitors (SMD, 1.23 [95% CI, 0.52–1.95]), stem cells (SMD, 1.64 [95% CI, 1.05–2.24]), antiplatelet or anticoagulant drugs (SMD, 0.93 [95% CI, 0.63–1.22]), and renin-angiotensin system inhibitors (SMD, 1.45 [95% CI, 0.58–2.33]) reduced AAA diameter. Interventions initiated soon after model induction commenced were more likely to reduce AAA diameter (R
2
, 16%;
P
=0.007). Funnel plots suggested possible publication bias. Most studies did not report blinding or sample size calculations, and the risk of bias was considered medium or high in 20 (57%) of the 35 studies.

Conclusions:
There is low-quality evidence that a range of drugs are effective in limiting AAA progression when administered early after AAA induction in mouse models. Some of these drugs, such as antiplatelet and renin-angiotensin system inhibitors, have been reported to be ineffective in clinical trials.
Values of Baseline Posterior Circulation Acute Stroke Prognosis Early Computed Tomography Score for Treatment Decision of Acute Basilar Artery Occlusion
Authors: Sang Hongfei , Li Fengli , Yuan Junjie , Liu Shuai , Luo Weidong , Wen Changming , Zhu Qiyi , Chen Wenhuo , Lin Min , Qi Li , Zhong Yaoyi , Wang Zhen , Ling Wentong , Shi Zhonghua , Chen Huisheng , Liu Wenhua , Liu Zhensheng , Yao Xiaoxi , Xiong Feng , Zeng Guoyong , Hu Xiaogang , Dong Hui , Mao An , Yang Guoqiang , Huang Jiacheng , Chen Luming , Gong Zili , Tao Jian , Liu Hansheng , Wu Deping , Qiu Zhongming , Yang Qingwu , Zi Wenjie , Li Fangfei 
Published: February 2021

Background and Purpose:
This study aimed to analyze the impact of baseline posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) on the efficacy and safety of endovascular therapy (EVT) for patients with acute basilar artery occlusion.

Methods:
The BASILAR was a nationwide prospective registry of consecutive patients with a symptomatic and radiologically confirmed acute basilar artery occlusion within 24 hours of symptom onset. We estimated the effect of standard medical therapy alone (SMT group) versus SMT plus EVT (EVT group) for patients with documented pc-ASPECTS on noncontrast CT, both as a categorical (0–4 versus 5–7 versus 8–10) and as a continuous variable. The primary outcomes included favorable functional outcomes (modified Rankin Scale ≤3) at 90 days and mortality within 90 days.

Results:

In total, 823 cases were included: 468 with pc-ASPECTS 8 to 10 (SMT: 71; EVT: 397), 317 with pc-ASPECTS 5 to 7 (SMT: 85; EVT: 232), and 38 with pc-ASPECTS 0 to 4 (SMT: 13; EVT: 25). EVT was associated with higher rate of favorable outcomes (adjusted relative risk with 95% CI, 4.35 [1.30–14.48] and 3.20 [1.68–6.09]; respectively) and lower mortality (60.8% versus 77.6%,
P
=0.005 and 35.0% versus 66.2%,
P<
0.001; respectively) than SMT in the pc-ASPECTS 5 to 7 and 8 to 10 subgroups. Continuous benefit curves also showed the superior efficacy and safety of EVT over SMT in patients with pc-ASPECTS ≥5. Furthermore, the prognostic effect of onset to puncture time on favorable outcome with EVT was not significant after adjustment for pc-ASPECTS (adjusted odds ratio, 0.98 [95% CI, 0.94–1.02]).

Conclusions:
Patients of basilar artery occlusion with pc-ASPECTS ≥5 could benefit from EVT. The baseline pc-ASPECTS appears more important for decision making and predicting prognosis than time to EVT.

Registration:

URL:
http://www.chictr.org.cn
. Unique identifier: ChiCTR1800014759.
Public–Private Inquiries: Institutional Intermediaries and the Transparency Nexus in Global Resource Development
Authors: Kemp Deanna , Owen John R. 
Published: February 2021

AbstractPrivately commissioned public inquiries in extractive industries are an enormously rich source of data for scholars of global environmental politics. This untapped arena comprises a series of unconventional inquiries in response to contentious socioenvironmental events and incidents, whereby large resource companies commission studies, relinquish control over the process, and publicly release findings. These inquiries are an episodic but persistent feature of the resource governance landscape in the global mining industry—one of the world’s most contentious, environmentally disruptive, and influential sectors. We argue that there is a certain independence or autonomy associated with these inquiries, justifying their analytical separation from internal corporate governance. Above all, these inquiries provide opportunities for scholars of global environmental politics to consolidate their activist roots and connect local realities to global debates. We offer a set of preliminary of research questions and describe points of access for future research.
Improvement of ERA5 over ERA-Interim in Simulating Surface Incident Solar Radiation throughout China
Authors: He Yanyi , Wang Kaicun , Feng Fei 
Published: February 2021

AbstractSurface incident solar radiation (Rs) is important for providing essential information on climate change. Existing studies have shown that the Rs values from current reanalyses are significantly overestimated throughout China. The European Centre for Medium-Range Weather Forecasts (ECMWF) recently released the fifth generation of atmospheric reanalysis (i.e., ERA5) with a much higher spatiotemporal resolution and a major upgrade compared to its predecessor, ERA-Interim. This study is to verify whether ERA5 can improve the Rs simulation using sunshine duration–derived Rs values at ~2200 stations over China from 1979 to 2014 as reference data. Compared with the observed multiyear national mean, the Rs overestimation is reduced from 15.88 W m−2 in ERA-Interim to 10.07 W m−2 in ERA5. From 1979 to 1993, ERA-Interim (−1.99 W m−2 decade−1; p < 0.05) and ERA5 (−2.42 W m−2 decade−1; p < 0.05) estimates of Rs in China continued to decrease and the decline of the latter is closer to the observed. After 1993, they both show a strong brightening (i.e., 2.26 W m−2 decade−1 in ERA-Interim and 1.49 W m−2 decade−1 in ERA5) but observations show a nonsignificant increase by 0.30 W m−2 decade−1. Due to the improvement of total cloud cover (TCC) simulation by ERA5, its Rs trend bias induced by the TCC trend bias is smaller than that in ERA-Interim. In addition, the reason why the simulation trend in ERA5 remains biased might be that ERA5 still ignores aerosol changes on interannual or decadal time scales. Therefore, subsequent reanalysis products still need to improve their simulation of clouds, water vapor, and aerosol, especially in aerosol direct and indirect effects on Rs.