bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer
Authors: Singer Christian F. ,   for the ABCSG, Holst Frederik , Steurer Stefan , Burandt Eike C. , Lax Sigurd F. , Jakesz Raimund , Rudas Margaretha , Stöger Herbert , Greil Richard ,   for the ABCSG, Sauter Guido , Filipits Martin ,   for the ABCSG, Simon Ronald , Gnant Michael ,   for the ABCSG
Published: August 2022

Abstract

Purpose:
Estrogen receptor (ER) expression is a prognostic parameter in breast cancer, and a prerequisite for the use of endocrine therapy. In ER+ early breast cancer, however, no receptor-associated biomarker exists that identifies patients with a particularly favorable outcome. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer.

Experimental Design:
394 patients who had been randomized into the tamoxifen-only arm of the prospective randomized ABCSG-06 trial of adjuvant endocrine therapy with available formalin-fixed, paraffin-embedded tumor tissue were included in this analysis. IHC ERα expression was evaluated both locally and in a central lab using the Allred score, while ESR1 gene amplification was evaluated by FISH analysis using the ESR1/CEP6 ratio indicating focal copy number alterations.

Results:
Focal ESR1 copy-number elevations (amplifications) were detected in 187 of 394 (47%) tumor specimens, and were associated with a favorable outcome: After a median follow-up of 10 years, women with intratumoral focal ESR1 amplification had a significantly longer distant recurrence-free survival [adjusted HR, 0.48; 95% confidence interval (CI), 0.26–0.91; P = 0.02] and breast cancer–specific survival (adjusted HR 0.47; 95% CI, 0.27–0.80; P = 0.01) as compared with women without ESR1 amplification. IHC ERα protein expression, evaluated by Allred score, correlated significantly with focal ESR1 amplification (P &lt; 0.0001; χ2 test), but was not prognostic by itself.

Conclusions:
Focal ESR1 amplification is an independent and powerful predictor for long-term distant recurrence-free and breast cancer–specific survival in postmenopausal women with endocrine-responsive early-stage breast cancer who received tamoxifen for 5 years.
Phototherapy with Cancer-Specific Nanoporphyrin Potentiates Immunotherapy in Bladder Cancer
Authors: Zhu Zheng , Ma Ai-Hong , Zhang Hongyong , Lin Tzu-Yin , Xue Xiangdong , Farrukh Hizra , Zhu Shaoming , Shi Wei , Yuan Ruan , Cao Zhixiu , Chittepu Veera Chandra Sekhar Reddy , Prabhala Rao , Li Yuanpei , Lam Kit S. , Pan Chong-xian 
Published: August 2022

Abstract

Purpose:
Immune checkpoint inhibitors (ICI) in general have shown poor efficacy in bladder cancer. The purpose of this project was to determine whether photodynamic therapy (PDT) with bladder cancer–specific porphyrin-based PLZ4-nanoparticles (PNP) potentiated ICI.

Experimental Design:
SV40 T/Ras double-transgenic mice bearing spontaneous bladder cancer and C57BL/6 mice carrying syngeneic bladder cancer models were used to determine the efficacy and conduct molecular correlative studies.

Results:
PDT with PNP generated reactive oxygen species, and induced protein carbonylation and dendritic cell maturation. In SV40 T/Ras double-transgenic mice carrying spontaneous bladder cancer, the median survival was 33.7 days in the control, compared with 44.8 (P = 0.0123), 52.6 (P = 0.0054), and over 75 (P = 0.0001) days in the anti-programmed cell death-1 antibody (anti-PD-1), PNP PDT, and combination groups, respectively. At Day 75 when all mice in other groups died, only 1 in 7 mice in the combination group died. For the direct anti-tumor activity, compared with the control, the anti-PD-1, PNP PDT, and combination groups induced a 40.25% (P = 0.0003), 80.72% (P &lt; 0.0001), and 93.03% (P &lt; 0.0001) tumor reduction, respectively. For the abscopal anticancer immunity, the anti-PD-1, PNP PDT, and combination groups induced tumor reduction of 45.73% (P = 0.0001), 54.92% (P &lt; 0.0001), and 75.96% (P &lt; 0.0001), respectively. The combination treatment also diminished spontaneous and induced lung metastasis. Potential of immunotherapy by PNP PDT is multifactorial.

Conclusions:
In addition to its potential for photodynamic diagnosis and therapy, PNP PDT can synergize immunotherapy in treating locally advanced and metastatic bladder cancer. Clinical trials are warranted to determine the efficacy and toxicity of this combination.
Modelos não adversariais de solução de conflitos sob o prisma da Administração Pública consensual
Authors: Borges Grazielly Almeida 
Published: August 2022

De acordo com a concepção de Administração Pública Consensual, o modelo de Administração impositiva vem sendo cada vez mais substituído pela noção de direito à boa governança à luz de uma gestão mais participativa e democrática. Considerando que a litigância excessiva do Estado se mostra como um desafio a ser enfrentado, a adoção de meios não adversariais de resolução de conflitos atenderia aos anseios sociais de participação, desafogaria o judiciário e resultaria em economia de recursos e eficiência na gestão dos conflitos por parte da Administração Pública.
A análise dos dados valeu-se dos métodos dedutivo, partindo da tese mais ampla de que a melhoria do Poder Judiciário depende da redução da litigiosidade excessiva do próprio Estado até alcançar a particularidade do acordo ou solução não adversarial; histórico-evolutivo, de modo a analisar brevemente os modelos antecedentes do objeto de estudo e dialético, ao analisar a compatibilidade do acordo com a indisponibilidade do interesse público e os parâmetros a serem seguidos na busca do consenso; sendo a pesquisa bibliográfica a técnica utilizada.
Hospital service utilisation of people previously hospitalised with different subtypes of psychotic disorder: A record linkage study
Authors: Srasuebkul Preeyaporn , Walker Adrian R , Cvejic Rachael C , Trollor Julian N , Lappin Julia M , Curtis Jackie , Samaras Katherine , Dean Kimberlie , Ward Philip B , Reppermund Simone 
Published: August 2022

Objective: Little research has examined the physical and mental comorbidities, and health service use patterns, of people diagnosed with psychotic disorder subtypes other than schizophrenia spectrum disorders. This study aims to examine the physical and mental comorbidities, and subsequent hospital service use patterns, of individuals previously hospitalised with various psychotic disorder subtypes using linked health service data. Methods: We included individuals hospitalised with a psychotic disorder in New South Wales, Australia, between 1 July 2002 and 31 December 2014 (N = 63,110). We examined the demographic profile of the cohort and rates of subsequent acute hospital care and ambulatory mental health service use. We compared the rates of subsequent hospital admissions, emergency department presentations and ambulatory mental health treatment days of people hospitalised with different psychotic disorder subtypes to people hospitalised with schizophrenia spectrum disorders using Poisson regression. Results: People most recently hospitalised with mood/affective disorders and psychotic symptoms had a higher rate of subsequent hospital admissions than those most recently hospitalised with schizophrenia spectrum and delusional disorders (adjusted incident rate ratio = 1.06; 95% confidence interval = [1.02, 1.10]), while people most recently hospitalised with drug-induced and other organic (adjusted incident rate ratio = 1.19; 95% confidence interval = [1.12, 1.27]) and acute psychotic disorders (adjusted incident rate ratio = 1.10; 95% confidence interval = [1.03, 1.18]) had more subsequent emergency department presentations than those most recently hospitalised with schizophrenia spectrum and delusional disorders. All three groups had fewer subsequent mental health ambulatory days than those most recently hospitalised with schizophrenia spectrum and delusional disorders (adjusted incident rate ratios = 0.85–0.91). Conclusion: The health profiles and subsequent hospital service use patterns of people previously hospitalised with different psychotic disorder subtypes are heterogeneous, and research is needed to develop targeted health policies to meet their specific health needs.
Use of venovenous extracorporeal membrane oxygenation in trauma patients with severe adult respiratory distress syndrome: A retrospective study
Authors: Lee Gil Jae , Kim Myung Jun , Lee Jae Gil , Lee Seung Hwan 
Published: August 2022

Background: The use of extracorporeal membrane oxygenation (ECMO) has increased, although its survival benefit in trauma patients with severe adult respiratory distress syndrome (ARDS) remains controversial. We investigated the effect of veno-venous (VV)-ECMO on the clinical outcomes of trauma patients with severe ARDS. Methods: This was a retrospective study at a single center comprising trauma patients admitted between January 2013 and December 2017, diagnosed with severe ARDS using the Berlin definition (PaO2/FiO2 ratio ⩽100), in the 7 days following trauma. Patients were managed with VV-ECMO or conventional mechanical ventilation (CMV). The primary outcome was in-hospital mortality (mortality at 60 days); secondary outcomes comprised 28-day mortality, hospital length of stay (LOS), intensive care unit (ICU) LOS, ICU-free days, duration of mechanical ventilation (MV), and MV-free days. Propensity score matching was performed to adjust for the baseline differences. Results: Sixteen patients (22.5%) were managed with VV-ECMO and 55 were managed with CMV. After matching, the in-hospital mortality rate (43.8% vs 53.1%; p = 0.760), 28-day mortality rate (37.5% vs 31.3%; p = 0.750), median hospital LOS (39.5 vs 36.5 days; p = 0.533), ICU-free days (0 vs 0 days; p = 0.241), and MV-free days (0 vs 0 days; p = 0.272) did not significantly differ between the VV-ECMO and CMV groups. Conclusion: In-hospital mortality (mortality at 60 days) did not differ significantly between the VV-ECMO and CMV groups. Although the safety of ECMO in trauma patients requires further investigation, VV-ECMO may be considered as a rescue therapy.
A new small sample test configuration for fatigue life estimation of overhead contact wires
Authors: Sunar Özgün , Fletcher David 
Published: August 2022

Fatigue in railway overhead line electrification (OLE) contact wires can cause sudden catastrophic failures. The contact wire interacting with the pantograph both mechanically and electrically is subjected to tension and repetitive bending due to the pantograph contact force. Recently, fatigue failures of OLE have risen in prominence with increases in train speed. To address this a new fatigue test configuration has been developed. The study focuses on a method for testing the wire as a component enabling fatigue life evaluation of worn wires, or exploring the effect of installation damage, through component level evaluation of crack initiation and propagation. The new test configuration places a 400 mm-length contact wire in a combination of bending and pretension with realistic boundary conditions replicating service conditions for longer spans. The results are presented in a strain-life format to provide data for a wide range of potential service conditions.
Appropriate supplementation of testosterone alleviates post-stroke damage via decreasing inflammation and oxidative stress in aged male C57BL/6 mice
Authors: Wang Jianguo , Zhou Yuefei , He Lijun 
Published: August 2022

Stroke injury is closely related to testosterone levels. Testosterone supplementation in elderly men is seen to protect the cardiovascular system and reduce the risk of stroke. But this medication method is controversial. This study aims to investigate the effect of long-term testosterone supplementation on brain injury after stroke in aged mice. 60 male C57BL/6 mice,12-months of age were divided into 3 groups: low-dose group, high-dose group, and control group, each group was injected subcutaneously with 100 μL of sesame oil or 5 mg/kg or 50 mg/kg of testosterone (in 100 μL of sesame oil) twice per week, respectively. One week after the injection, stroke was induced by light. After the stroke, the injection continued for 6 weeks. The motion ability was measured by rotating rod and tail suspension. The brain injury was observed by naked eyes and TTC staining. In addition, we measured the inflammation ( Tnf-α, Il-6, and Mcp-1) and oxidative stress (Malondialdehyde (MDA) and T-AOC) in the injured tissue 72 h post-stroke. Low-dose testosterone supplementation improved the motion ability and decreased brain injury. It also decreased the inflammatory factors ( Tnf-α, Il-6, and Mcp-1), decreased MDA product, and increased T-AOC. High-dose testosterone supplementation not only reduced the motion ability and aggravated stroke injury, but also increased the inflammation, MDA level and decreased T-AOC level. In summary, supplementation of testosterone at normal levels in elderly mice can alleviate post-stroke injury by reducing inflammation and oxidative stress; however, excessive supplementation may cause unexpected injuries. This study has important implications for the application of testosterone replacement therapy.
A rapid, easy, and scalable whole blood monocyte CD169 assay for outpatient screening during SARS-CoV-2 outbreak, and potentially other emerging disease outbreaks
Authors: Michel Moïse , Malergue Fabrice , Ait Belkacem Inès , Bourgoin Pénélope , Morange Pierre-Emmanuel , Arnoux Isabelle , Miloud Tewfik , Million Matthieu , Tissot-Dupont Hervé , Mege Jean-Louis , Vitte Joana , Busnel Jean-Marc 
Published: August 2022

Objective: The COVID-19 corona virus disease outbreak is globally challenging health systems and societies. Its diagnosis relies on molecular methods, with drawbacks revealed by mass screening. Upregulation of neutrophil CD64 or monocyte CD169 has been abundantly reported as markers of bacterial or acute viral infection, respectively. We evaluated the sensitivity of an easy, one-step whole blood flow cytometry assay to measure these markers within 10 min, as a potential screening test for COVID-19 patients. Methods: Patients ( n = 177) with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were tested on 10 µL blood and results were compared with reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Results: We observed 98% and 100% sensitivity in early-stage ( n = 52) and asymptomatic patients ( n = 9), respectively. Late-stage patients, who presented for a second control RT-qPCR, were negative for both assays in most cases. Conversely, neutrophil CD64 expression was unchanged in 75% of cases, without significant differences between groups. Conclusion: Monocyte CD169 evaluation was highly sensitive for detecting SARS-CoV-2 infection in first-presentation patients; and it returns to basal level upon infection clearance. The potential ease of fingerprick collection, minimal time-to-result, and low cost rank this biomarker measurement as a potential viral disease screening tool, including COVID-19. When the virus prevalence in the tested population is usually low (1%−10%), such an approach could increase the testing capacity 10 to 100-fold, with the same limited molecular testing resources, which could focus on confirmation purposes only.
Estimating Productivity Loss from Breast and Non–Small-Cell Lung Cancer among Working-Age Patients and Unpaid Caregivers: A Survey Study Using the Multiplier Method
Authors: Chiu Kevin , MacEwan Joanna P. , May Suepattra G. , Bognar Katalin , Peneva Desi , Zhao Lauren M. , Yong Candice , Amin Suvina , Bolinder Bjorn , Batt Katharine , Baumgardner James R. 
Published: August 2022

Background. Traditional approaches to capturing health-related productivity loss (e.g., the human capital method) focus only on the foregone wages of affected patients, overlooking the losses caregivers can incur. This study estimated the burden of productivity loss among breast cancer (BC) and non–small-cell lung cancer (NSCLC) patients and individuals caring for such patients using an augmented multiplier method. Design. A cross-sectional survey of BC and NSCLC patients and caregivers measured loss associated with time absent from work (absenteeism) and reduced effectiveness (presenteeism). Respondents reported pre- and postcancer diagnosis income, hours worked, and time to complete tasks. Exploratory multivariable analyses examined correlations between respondents’ clinical/demographic characteristics—including industry of employment—and postdiagnosis productivity. Results. Of 204 patients (104 BC, 100 NSCLC) and 200 caregivers (100 BC, 100 NSCLC) who completed the survey, 319 participants (162 BC, 157 NSCLC) working ≥40 wk/y prediagnosis were included in the analysis. More than one-third of the NSCLC (33%) and BC (43%) patients left the workforce postdiagnosis, whereas only 15% of caregivers did. The traditional estimate for the burden of productivity loss was 66% lower on average than the augmented estimate (NSCLC patients: 60%, BC patients: 69%, NSCLC caregivers: 59%, and BC caregivers: 73%). Conclusions. Although patients typically experience greater absenteeism, productivity loss incurred by caregivers is also substantial. Failure to account for such impacts can result in substantial underestimation of productivity gains novel cancer treatments may confer by enabling patients and caregivers to remain in the workforce longer. Our results underscore the importance of holistic approaches to understanding this impact on both patients and their caregivers and accounting for such considerations when making decisions about treatment and treatment value. Highlights Cancer can have a profound impact on productivity. This study demonstrates how the disease affects not only patients but also the informal or unpaid individuals who care for patients. An augmented approach to calculating health-related productivity loss suggests that productivity impacts are much larger than previously understood. A more comprehensive understanding of the economic burden of cancer for both patients and their caregivers suggests the need for more support in the workplace for these individuals and a holistic approach to accounting for these impacts in treatment decision making.
Recent insights into the microRNA-dependent modulation of gliomas from pathogenesis to diagnosis and treatment
Authors: Mafi Alireza , Rahmati Atefe , Babaei Aghdam Zahra , Salami Raziyeh , Salami Marziyeh , Vakili Omid , Aghadavod Esmat 
Published: August 2022

AbstractGliomas are the most lethal primary brain tumors in adults. These highly invasive tumors have poor 5-year survival for patients. Gliomas are principally characterized by rapid diffusion as well as high levels of cellular heterogeneity. However, to date, the exact pathogenic mechanisms, contributing to gliomas remain ambiguous. MicroRNAs (miRNAs), as small noncoding RNAs of about 20 nucleotides in length, are known as chief modulators of different biological processes at both transcriptional and posttranscriptional levels. More recently, it has been revealed that these noncoding RNA molecules have essential roles in tumorigenesis and progression of multiple cancers, including gliomas. Interestingly, miRNAs are able to modulate diverse cancer-related processes such as cell proliferation and apoptosis, invasion and migration, differentiation and stemness, angiogenesis, and drug resistance; thus, impaired miRNAs may result in deterioration of gliomas. Additionally, miRNAs can be secreted into cerebrospinal fluid (CSF), as well as the bloodstream, and transported between normal and tumor cells freely or by exosomes, converting them into potential diagnostic and/or prognostic biomarkers for gliomas. They would also be great therapeutic agents, especially if they could cross the blood–brain barrier (BBB). Accordingly, in the current review, the contribution of miRNAs to glioma pathogenesis is first discussed, then their glioma-related diagnostic/prognostic and therapeutic potential is highlighted briefly.
Multi-scaled self-attention for drug–target interaction prediction based on multi-granularity representation
Authors: Zeng Yuni , Chen Xiangru , Peng Dezhong , Zhang Lijun , Huang Haixiao 
Published: August 2022

AbstractBackgroundDrug–target interaction (DTI) prediction plays a crucial role in drug discovery. Although the advanced deep learning has shown promising results in predicting DTIs, it still needs improvements in two aspects: (1) encoding method, in which the existing encoding method, character encoding, overlooks chemical textual information of atoms with multiple characters and chemical functional groups; as well as (2) the architecture of deep model, which should focus on multiple chemical patterns in drug and target representations.ResultsIn this paper, we propose a multi-granularity multi-scaled self-attention (SAN) model by alleviating the above problems. Specifically, in process of encoding, we investigate a segmentation method for drug and protein sequences and then label the segmented groups as the multi-granularity representations. Moreover, in order to enhance the various local patterns in these multi-granularity representations, a multi-scaled SAN is built and exploited to generate deep representations of drugs and targets. Finally, our proposed model predicts DTIs based on the fusion of these deep representations. Our proposed model is evaluated on two benchmark datasets, KIBA and Davis. The experimental results reveal that our proposed model yields better prediction accuracy than strong baseline models.ConclusionOur proposed multi-granularity encoding method and multi-scaled SAN model improve DTI prediction by encoding the chemical textual information of drugs and targets and extracting their various local patterns, respectively.