bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multi- institutional Prospective Analysis of Impact of CanAssist Breast (Morphometric Immunohistochemistry Based Test) on Adjuvant Chemotherapy Decisions in Early Breast Cancer
Authors: SP Somashekhar , Patil Shekhar , Thippeswamy Ravi , Rajeevkumar Rajeevkumar , Agrawal Chaturbhuj R , Doval Dinesh Chandra , DG Vijay , Bapna Ajay , Shankar Kiran , CB Avinash , Udapa Karthik S , Prasad Krishna 
Published: May 2021

Abstract
Purpose: CanAssist Breast (CAB) has been validated retrospectively for assessing risk of recurrence and thereby usefulness of chemotherapy in HR+/HER2- breast cancer. The objective of this study is to assess the agreement between physician’s treatment plan and CAB risk stratification and evaluate whether CAB results aid in the physician’s treatment decision.Methods: The data on the physician’s treatment plan before and after the CAB test was collected prospectively between 2016 and 2021 in 249 patients. Changes in treatment recommendations and compliance with CAB reports were analyzed. Results: Based on conventional clinicopathological features physicians planned to treat 46% of patients with endocrine therapy (ET) (low-risk-LR)), 24% with chemoendocrine therapy (CET) (high-risk-HR)) and in 30% physicians were uncertain of prescribing chemotherapy (intermediate-risk-IR)) before CAB testing. The correlation between clinical risk assessment and CAB risk stratification (k=0.2 (0.05-0.35) was nonsignificant. CAB classified 64% as LR, which was 18% (9.3-25, P=0.0001) higher compared to clinical LR. In the clinical IR category, CAB risk proportions were 55:45 (LR: HR). We observed a substantial shift in treatment recommendation from CET to ET in 54% (40.75- 66.84, P<0.0001) of clinical HR and ET to CET in 26% (18.27- 35.01, P<0.0001) of clinical LR patients. Overall CAB lead to change in treatment recommendation in 42% of the cohort.Conclusions: There was a significant impact of CAB on the physician’s treatment decision. CAB provided definite treatment recommendation to IR patients where the physician had dilemma on prescribing chemotherapy and provided precise treatment plan to clinical LR and HR patients.
A Comparison Between Tau and Amyloid-β Cerebrospinal Fluid Biomarkers in Chronic Traumatic Encephalopathy and Alzheimer Disease
Authors: Turk Katherine W. , Geada Alexandra , Alvarez Victor E. , Xia Weiming , Cherry Jonathan D. , Nicks Raymond , Meng Gaoyuan , Daley Sarah , Tripodis Yorghos , Huber Bertrand R. , Budson Andrew E. , Dwyer Brigid , Kowall Neil W. , Cantu Robert C. , Goldstein Lee E. , Katz Douglas I. , Stern Robert A. , Alosco Michael L. , Mez Jesse , McKee Ann C. , Stein Thor D. 
Published: May 2021

Abstract
Background
Cerebrospinal fluid (CSF) tau and beta-amyloid levels in chronic traumatic encephalopathy (CTE), a disease which can be clinically indistinguishable from Alzheimer’s disease (AD), are largely unknown. We examined postmortem CSF analytes among participants with autopsy confirmed CTE and AD.
Methods
In this cross-sectional study 192 participants from the Boston University AD Research Center, VA-BU-CLF Center, and Framingham Heart Study (FHS) had post-mortem CSF collected at autopsy. Participants were divided into pathological groups based on AD and CTE criteria, with 61 CTE participants (18 low, 43 high stage), 79 AD participants (23 low, 56 intermediate to high), 11 participants with CTE combined with AD, and 41 participants lacking both CTE and AD neuropathology. The Meso Scale Discovery immunoassay system was utilized to measure amyloid-beta (Aβ1 − 40, Aβ1 − 42), total tau (t-tau), and phosphorylated tau (p-tau181 and p-tau231). CSF analytes were then compared across the six pathological groups: no CTE/no AD, Low CTE, Low AD, High CTE, Intermediate/High AD, and AD + CTE.
Results
The low CTE group had higher levels of p-tau231 compared no CTE/no AD (p < 0.001), and compared to the low AD group (p = 0.002). The low CTE group had lower levels of Aβ1−42 compared to no CTE/no AD (p = 0.009). The high CTE group had higher levels of p-tau231 compared to intermediate/high AD (p < 0.001).
Conclusions
Importantly, p-tau231 and Aβ1−42 were predictors of diagnosis of CTE vs. no CTE/no AD and CTE vs. AD. Increased CSF p-tau231 is a promising potentially sensitive biomarker of CTE, and CSF Aβ1−42 needs further investigation in CTE.
Single Versus Multiple Doses of Tocilizumab in Critically Ill Patients with Coronavirus Disease 2019 (COVID-19): A Two-center, Retrospective Cohort Study
Authors: Sulaiman Khalid Al , Juhani Ohoud Al , Salah Khalid Bin , Koryem Ghazwa , Eljaaly Khalid , Essa Mohammed Al , Kharbosh Abdullah , Harbi Feras Al , Abuzaid Maram , Bilal Sarah Al , Magthali Alaa , Alsohemi Samia , Alshabasy Adel , Albossiry Hyatham , Abodeif Mohammed , Alshehri Asma , Vishwakarma Ramesh 
Published: May 2021

Abstract
Background: In COVID-19 patients, increased IL-6 levels have been associated with poor disease prognosis. The use of tocilizumab shown to be effective in treating COVID-19 with varying success. This study aims to evaluate the effectiveness and safety of using a single dose of tocilizumab compared with multiple doses in critically ill COVID-19 patients.Methods:This study is a two-center, retrospective cohort, in which patients who received tocilizumab and were admitted to the ICU at two tertiary hospitals from March 1st, 2020, until January 31st, 2021were included. Patients were divided into two groups based on the number of doses of tocilizumab they received. Furthermore, we gathered additional data from the patients, such as but not limited to demographic data, vital signs, and laboratory markers. Multivariable logistic and generalized linear regression were used. We considered a P value of < 0.05 statistically significant. Results: Two hundred sixty-one patients were included in this study; 72.4% received a single dose of tocilizumab, while the rest (27.6%) had received multiple doses. Most of the patients were male, with an average age of 59.2. After adjusting for possible confounders, the ICU mortality within 30 days (OR 0.83; 95% CI, 0.33-2.08 p = 0.69) and in-hospital mortality (OR 0.64; 95% CI, 0.26-1.60 p = 0.35) were not significantly different between the two groups. On the flip side, patients who received multiple doses of tocilizumab have higher odds of secondary infection compared with a single dose (OR 3.06; 95% CI, 1.18-7.89 p = 0.02).Conclusion: Multiple doses of tocilizumab were not associated with a statistically significant difference in ICU and hospital mortality in critically ill patients infected with COVID-19. In contrast, it was associated with higher odds of secondary infections compared to a single dose.
Clinical course and outcomes of secondary bloodstream infection patients with COVID-19 in Wuhan, China: A retrospective study
Authors: Li Jie , Wang Junwei , Yang Yi , Cai Peishan , Cao Jingchao , Wu Sanlan , Zhang Yu , Cai Xuefeng 
Published: May 2021

Abstract
Background

Secondary bloodstream infection (SBI) is considered one of the most perilous complications of coronavirus disease 2019 (COVID-19). Although the etiology of SBI has been reported, the clinical course and outcomes of this illness have not been well described.
Methods

In this retrospective study, all patients with confirmed SBI were included from a cohort of 1,651 patients hospitalized with COVID-19 in the Wuhan Union Hospital between January 25 and April 23, 2020. Demographics, clinical features, laboratory findings, treatments and outcomes were extracted from electronic medical records. The data were compared between survivors and non-survivors based on whether patients died within 30 days following SBI onset.
Results

A total of 31 patients corresponding to 1.9% (31/1,651) who exhibited SBI were included in the present study. The median time from admission to the onset of SBI was 22.0 days (2.0–64.0). The most common symptoms were shortness of breath (74%), fever (65%) and decreased blood pressure (52%) at the onset of SBI. The levels of white blood cell count, C-reactive protein, and procalcitonin were mostly elevated. Carbapenem-resistant Klebsiella pneumoniae (15 [48%]) and Acinetobacter baumannii (7 [23%]) were the main pathogens. In empirical treatment, carbapenems were still the first choice. The 30-day mortality following SBI onset and the hospital mortality of the 31 patients were 67.7% (21/31) and 77.4% (24/31), respectively. Almost every patient with SBI had complication due to sepsis (28 [90%]). The median time periods to sepsis and septic shock were 1 days (1.0 ~ 5.0) and 3.0 days (1.0 ~ 12.0), respectively. The proportion of carbapenem-resistant gram-negative bacteria (CRGNB) detected in blood cultures of non-survivors was higher (18 [86%] vs. 4 [40%]) compared to that of the survivors. These patients were more likely to develop sepsis (21 [100%] vs. 7 [70%]), and acute cardiac injury (19 [90%] vs. 5 [50%]).
Conclusions

The mortality of SBI patients with COVID-19 is considerable. Increased risk of mortality was noted for the following three subgroups: Patients infected with CRGNB, patients with complications of sepsis and patients with acute cardiac injury.
PTEN Loss Correlates with T cell Exclusion across Human Cancers
Authors: Lin Ziying , Huang Lixia , Li ShaoLi , Gu Jincui , Cui Xiaoxian , Zhou Yanbin 
Published: May 2021

Abstract
Background: Recent evidences had shown that loss in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was associated with immunotherapy resistance, which may be attributed to the non-T-cell-inflamed tumor microenvironment. The impact of PTEN loss on tumor microenvironment, especially regarding T cell infiltration across tumor types is not well understood.Methods: Utilizing The Cancer Genome Atlas (TCGA) and publicly available dataset of immunotherapy, we explored the correlation of PTEN expressing level or genomic loss with tumor immune microenvironment and response to immunotherapy. We further investigated the involvement of PI3K-AKT-mTOR pathway activation, which is known to be the subsequent effect of PTEN loss, in the immune microenvironment modulation.Results: We reveal that PTEN mRNA expression is significantly positively correlated with CD4/CD8A gene expression and T cells infiltration especially T helpers cells, central memory T cell and effector memory T cells in multiples tumor types. Genomic loss of PTEN is associated with reduced CD8+ T cells, type 1 T helper cells, and increased type 2 T helper cells, immunosuppressed genes (e.g. VEGFA) expression. Furthermore, T cell exclusive phenotype is also observed in tumor with PI3K pathway activation or genomic gain in PIK3CA or PIK3CB. PTEN loss and PI3K pathway activation correlate with immunosuppressive microenvironment, especially in terms of T cell exclusion. PTEN loss predict poor therapeutic response and worse survival outcome in patients receiving immunotherapy.Conclusion: These data brings insight into the role of PTEN loss in T cell exclusion and immunotherapy resistance, and inspires further research on immune modulating strategy to augment immunotherapy.
One-Year and Consequences of COVID-19 in Cancer Patients: a Cohort Study
Authors: Chai Chen , Feng Xiaojun , Lu Meixia , Li Shoupeng , Chen Kui , Wang Hongxiang , Wang Wendan , Tang Zhaoming , Cheng Gang , Wu Xiaoxiong , Li Yunfeng , Wen Yuying , Da Banghong , Fan Hong , Wang Lei , Ai Fen , Li Wei , Peng Cao , Zhang Hongrong , Wen Shuang , Zhang Jinnong , Weng Yuxiong , Tang Zehai 
Published: May 2021

Abstract
Background

The study aim was to investigate one-year all-cause mortality and health consequences of cancer COVID-19 patients in China, stratified by primary tumor subtype.
Methods

In this multicenter cohort study, 166 cancer COVID-19 patients were studied along with 498 gender- and age-matched non-cancer COVID-19 patients in four hospitals in Wuhan, China, admitted 2020/01/01-2020/03/18, as well as with 498 parallel gender-, age-, and cancer subtype- matched non-COVID cancer patients hospitalized between 2019/01/01-2020/03/17. All patients were followed-up with a telephone survey to assess health consequences. Cox proportional hazards regression were used for risk analysis.
Results

In the three cohorts of median age of 65 ± 1 year and 49% male, the one-year all-cause mortality and hospital mortality rates of Cancer COVID-19 Cohort, 30% and 20% respectively, were significantly higher than COVID-19 Cohort (9% and 8%), and Cancer Cohort (16% and 2%). The 12-month all-cause post-discharge mortality rate of Cancer COVID-19 Cohort (11%) was higher than COVID-19 Cohort (0.4%), but similar to Cancer Cohort (15%). The high 1-year all-cause mortality was among hematologic malignancies (65%) and then nasopharyngeal, brain and skin tumors (45%), digestive system (43%), and lung (32%). the rate was low among genitourinary (14%), female genital (13%), breast (11%), and thyroid (0). As for patients having at least one symptom at the 1-year follow-up, Cancer COVID-19 Cohort (23%, 26/114) is similar to COVID-19 Cohort (30%, 130/432).
Discussion

Cancer COVID-19 patients showed a high rate of hospitalization mortality, but not after discharged, signifying the strong acute adverse effect of COVID-19 on cancer patients while little was in long-term effect. Risk stratification showed that hematologic malignancies, nasopharyngeal, brain, digestive system and lung tumors were high risk, while genitourinary, female genital, breast and thyroid were low risk which was similar to non-cancer COVID-19.
Conclusions

COVID-19 had little effect of 1-year mortality and sequelae for cancer survivors discharged from SARS-CoV-2 virus infection. Different tumor subtypes had different effect of COVID-19. COVID-19 patients with thyroid, breast, female genital, genitourinary tumor had low risk mortality which was similar to non-cancer patients.
Long-Term Survival in Extensive Disease Small Cell Lung Cancer Patients Treated Without Immune Checkpoint Inhibitors
Authors: Wakuda Kazushige , Yabe Michitoshi , Kodama Hiroaki , Nishioka Naoya , Miyawaki Taichi , Miyawaki Eriko , Mamesaya Nobuaki , Kobayashi Haruki , Omori Shota , Ono Akira , Kenmotsu Hirotsugu , Naito Tateaki , Murakami Haruyasu , Shimizu Tetsuo , Gon Yasuhiro , Takahashi Toshiaki 
Published: May 2021

Abstract
Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have been approved as first-line treatment for patients with untreated extensive disease-small cell lung cancer (ED-SCLC). However, there are few reports about the long-term survival in patients with ED-SCLC treated without ICIs. Thus, we analyzed the long-term survival in patients with ED-SCLC.Methods: We retrospectively examined the medical records of patients with SCLC who were treated at our hospital between September 2002 and September 2019. The main inclusion criteria were as follows: (1) histological or cytological confirmation of SCLC, (2) diagnosed with ED-SCLC, and (3) received chemotherapy, not including ICIs, as the first-line treatment. To assess the trends of treatment outcomes, we compared the survival outcomes between 2002–2010 (early) and 2011–2019 (late) groups.Results: A total of 314 patients were included in this study. Patient characteristics at the time of first-line treatment were as follows: median age was 69 years; 82% of the patients were male; and 70% had a performance status of 0 or 1. The median follow-up time of overall survival (OS) was 7.4 years, and 89% of the patients died. The median progression-free survival and survival time were 4.9 months and 12.1 months, respectively. Five-year survival rate was 2%. There was no significant difference in survival between the early and late groups.Conclusion: We found that the long-term survival in ED-SCLC patients treated without ICIs was poor. Prior to the approval of ICI treatment for ED-SCLC, there was no improvement in the OS for approximately 20 years.
The Predictive Value of Tumor Volume, Inflammatory Biomarkers, and Their Dynamic Changes on Early Tumor Response for Elderly Patients With Esophageal Squamous Cell Carcinoma Underwent Radiotherapy
Authors: Liang Shuai , Li Chengming , Wang Lu , Xu Dongshui , Liu Zhao , Meng Xue 
Published: May 2021

Abstract
Background: To investigate the tumor volume, pre-treatment inflammatory biomarkers (pre-IBs), and their dynamic changes on early tumor response (ETR) in elderly patients (≥70 years) with esophageal squamous cell carcinoma (ESCC) underwent radiotherapy.Methods: The ETR was assessed according to RECIST 1.1 at 1 month after radiotherapy. The tumor volume ((gross tumor volume (GTV) at the initial treatment planning (GTVi), and GTV at shrinking irradiation field planning (GTVs)), IBs (neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), and lymphocyte/monocyte (LMR)) which also included during treatment IBs (dur-IBs), and clinical variables were collected and analyzed from 197 patients received radiotherapy at our institution between 2015 and 2020. The tumor volume change rate (TVCR) and dynamic changes of IBs (delta-IBs) were defined as follows: TVCR=(1-GTVs/GTVi)×100%, delta-IBs=1-dur-IBs/pre-IBs. A nomogram based on logistic regression analysis were then established for predicting ETR.Results: GTVi and pre-LMR significantly decreased, pre-NLR, and pre-PLR significantly increased during radiotherapy or chemoradiotherapy (all P<0.001). Multivariate analysis indicated that TVCR [OR, 0.197; 95%CI, 0.093-0.414; P<0.001], pre-NLR [OR, 2.568; 95%CI, 1.031-6.394; P=0.043], and delta-NLR [OR, 2.831; 95%CI, 1.126-7.119; P=0.027] were statistically significant with ETR. And c-index of the nomogram established by combining all independent predictors for ETR was 0.769 [95%CI, 0.161–0.302].Conclusion: TVCR, Pre-NLR, and delta-NLR were significant with ETR in elderly patients with ESCC who underwent radiotherapy. And the developed nomogram with superior prediction ability for ETR could assist in patients counseling and guide to make individual treatments and follow-up strategies.
Non-Fourier heat transfer enhancement in Power law fluid with mono and hybrid nanoparticles
Authors: Sadiq M. Adil 
Published: May 2021

Abstract
Several polymers like ethylene glycol exhibit non-Newtonian rheological behaviors. Ethylene glycol is a world-widely used engine coolant and therefore, investigation of thermal enhancement by dispersing mono and hybrid nanoparticles in ethylene glycol is worthful. Since, ethylene glycol has shear rate-dependent viscosity and it obeys the power law rheological model. Therefore, based on these facts, the power-law rheological model is used with thermophysical properties are augmented with basic laws of heat transfer in fluid for the modeling of considered physical situations. M oS 2 are taken as mono-nanoparticles where M oS 2 and SiO 2 are taken as hybrid nano-sized particles. Comparative study for the enhancement of thermal performance of M oS 2 ethylene glycol and M oS 2 −SiO 2 − ethylene glycol is done. For energy conservation, non-Fourier’s law of Cattaneo-Christov is used. Power law fluid becomes more heat generative due to dispersion of M oS 2 and SiO 2. However, M oS 2 −power law fluid is less heat generative relative to M oS 2 − SiO 2-nanofluid. Thermal relaxation time is found proportional to the ability of the fluid to restore its thermal equilibrium.
Ageing on the Frontlines: Examining the Experiences of Older Frontline Healthcare Workers in Singapore General Hospital During The COVID-19 Pandemic.
Authors: Charles Gerard , Wen Sophia Lau Pei 
Published: May 2021

Abstract
Objectives: The first aim of this study was to understand the psychosocial impacts faced by our older healthcare frontline workers during the COVID-19 pandemic in Singapore General Hospital. Secondly, we hoped to explore the issues faced by an ageing healthcare workforce and recommend improvements in daily operations for future health crises. Lastly, we wanted to analyse ageist attitudes and misconceptions of being an older adult and recommend future changes in organizational policies.Methods: This is a mixed-methods cross-sectional survey. A self-designed questionnaire was developed by the study team through FormSG. It consists of 9 open and 45 closed-ended questions. Data were collected during the months of December 2020 and January 2021. Healthcare workers aged 62 years old and above were eligible to participate in this study by scanning a QR code or via weblink.Results: Participants had expressed mixed feelings while working during the COVID-19 pandemic such as uncertainty (75%), anxiety (58%), fear (42%), stress (25%), and sadness (25%). 75% of the participants went on to acknowledge that due to their job, their loved ones would be at a higher risk of contracting COVID-19. Similarly, 75% responded that they were determined to do their duty as a frontline healthcare worker despite fears of being diagnosed with COVID-19 present amongst 33% of the participants. 25% of participants felt motivated to be frontline healthcare workers with no reports of any form of discrimination from the public. 92% of the participants were aware that due to their age, they stood a much higher chance of contracting COVID-19 and had not considered being deployed to a lower risk area in fears of their health. All participants had taken part in the annual flu vaccination program, with 58% of responses indicating they believe the annual flu vaccination can prevent them from contracting COVID-19.Conclusion: Older adults bring forth a wealth of experiences in any organisation, however, as much experience as there may be, the ageing process is also accompanied by a myriad of complex challenges. Having strong social, professional, and familial support has allowed older adults to tide through this pandemic psychosocially. It is of utmost importance to understand the strengths and unique challenges that come with working in an intergenerational workforce, despite so the intergenerational economy can flourish with proper management skills and job re-designing, re-tooling, and re-skilling resources to ensure the right fit to employability skills and staff loyalty. Moreover, even younger staff will age through time.