bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival Outcomes in Oral Tongue Cancer: A Mono-Institutional Experience Focusing on Age
Authors: Ansarin Mohssen , De Berardinis Rita , Corso Federica , Giugliano Gioacchino , Bruschini Roberto , De Benedetto Luigi , Zorzi Stefano , Maffini Fausto , Sovardi Fabio , Pigni Carolina , Scaglione Donatella , Alterio Daniela , Cossu Rocca Maria , Chiocca Susanna , Gandini Sara , Tagliabue Marta 
Published: April 2021

ObjectiveThe prognostic role of age among patients affected by Oral Tongue Squamous Cell Carcinoma (OTSCC) is a topic of debate. Recent cohort studies have found that patients diagnosed at 40 years of age or younger have a better prognosis. The aim of this cohort study was to clarify whether age is an independent prognostic factor and discuss heterogeneity of outcomes by stage and treatments in different age groups.MethodsWe performed a study on 577 consecutive patients affected by primary tongue cancer and treated with surgery and adjuvant therapy according to stage, at European Institute of Oncology, IRCCS. Patients with age at diagnosis below 40 years totaled 109 (19%). Overall survival (OS), disease-free survival (DFS), tongue specific free survival (TSFS) and cause-specific survival (CSS) were compared by age groups. Multivariate Cox proportional hazards models were used to assess the independent role of age.ResultsThe median follow-up time was 5.01 years (range 0–18.68) years with follow-up recorded up to February 2020. After adjustment for all the significant confounding and prognostic factors, age remained independently associated with OS and DSF (respectively, p = 0.002 and p = 0.02). In CSS and TSFS curves, the role of age seems less evident (respectively, p = 0.14 and p = 0.0.37). In the advanced stage sub-group (stages III–IV), age was significantly associated with OS and CSS with almost double increased risk of dying (OS) and dying from tongue cancer (CSS) in elderly compared to younger groups (OS: HR = 2.16 95%, CI: 1.33–3.51, p= 0.001; CSS: HR = 1.76 95%, CI: 1.03–3.01, p = 0.02, respectively). In our study, young patients were more likely to be treated with intensified therapies (glossectomies types III–V and adjuvant radio-chemotherapy). Age was found as a prognostic factor, independently of other significant factors and treatment. Also the T–N tract involved by disease and neutrophil-to-lymphocyte ratio ≥3 were independent prognostic factors.ConclusionsYoung age at diagnosis is associated with a better overall survival. Fewer younger people than older people died from tongue cancer in advanced stages.
A Personalized, Dynamic Physical Activity Intervention Is Feasible and Improves Energetic Capacity, Energy Expenditure, and Quality of Life in Breast Cancer Survivors
Authors: Ballinger Tarah J. , Althouse Sandra K. , Olsen Timothy P. , Miller Kathy D. , Sledge Jeffrey S. 
Published: April 2021

PurposeDespite survival and quality of life benefits associated with physical activity, many breast cancer survivors remain inactive. Effective, sustainable interventions must account for individual differences in capability, motivation, and environment. Here, we evaluate the feasibility, mechanics, and efficacy of delivering an individualized, dynamic intervention to increase energetic capacity and energy expenditure.MethodsStage 0–III breast cancer patients who had completed primary treatment were enrolled. Prior to the intervention, detailed movement data was collected with a wearable GPS and accelerometer for 3 weeks to establish baseline activity. Movement data was collected continuously throughout the 12-week intervention, during which patients received electronically delivered, tailored, dynamic activity “prescriptions”, adjusted based on demonstrated individual capability, daily movement in their environment, and progress.ResultsOf 66 enrolled, 57 participants began and completed the intervention. The intervention resulted in significant improvements in average steps (+558 steps/day, p = 0.01), energetic capacity measured by power generation on a stationary bicycle (1.76 to 1.99 W/kg lean mass, p &lt; 0.01), and quality of life (FACT-B TOI, 72.8 to 74.8, p = 0.02). The greatest improvement in functional energetic capacity was seen in the lowest performing tertile at baseline (0.76 to 1.12 W/kg, p &lt; 0.01).DiscussionWearable technology delivery of personalized activity prescriptions based on individual capability and movement behaviors demonstrates feasibility and early effectiveness. The high variability seen in baseline activity and function, as well as in response to the intervention, supports the need for future work in precision approaches to physical activity (NCT03158519).
Diagnosis of Non-Hepatocellular Carcinoma Malignancies in Patients With Risks for Hepatocellular Carcinoma: CEUS LI-RADS Versus CT/MRI LI-RADS
Authors: Hu Yi-Xin , Shen Jing-Xian , Han Jing , Mao Si-Yue , Mao Ru-Shuang , Li Qing , Li Fei , Guo Zhi-Xing , Zhou Jian-Hua 
Published: April 2021

ObjectiveData regarding direct comparison of contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and Computed Tomography/Magnetic Resonance Imaging (CT/MR) LI-RADS in diagnosis of non-hepatocelluar carcinoma (non-HCC) malignancies remain limited. Our study aimed to compare the diagnostic performance of the CEUS LI-RADS version 2017 and CT/MRI LI-RADS v2018 for diagnosing non-HCC malignancies in patients with risks for HCC.Materials and MethodsIn this retrospective study, 94 liver nodules pathologically-confirmed as non-HCC malignancies in 92 patients at risks for HCC from January 2009 to December 2018 were enrolled. The imaging features and the LI-RADS categories on corresponding CEUS and CT/MRI within 1 month were retrospectively analyzed according to the ACR CEUS LI-RADS v2017 and ACR CT/MRI LI-RADS v2018 by two radiologists in consensus for each algorithm. The sensitivity of LR-M category, inter-reader agreement and inter-modality agreement was compared between these two standardized algorithms.ResultsNinety-four nodules in 92 patients (mean age, 54 years ± 10 [standard deviation] with 65 men [54 years ± 11] and 27 women [54 years ± 8]), including 56 intrahepatic cholangiocarcinomas, 34 combined hepatocellular cholangiocarcinomas, two adenosquamous carcinomas of the liver, one primary hepatic neuroendocrine carcinoma and one hepatic undifferentiated sarcoma were included. On CEUS, numbers of lesions classified as LR-3, LR-4, LR-5 and LR-M were 0, 1, 10 and 83, and on CT/MRI, the corresponding numbers were 3, 0, 14 and 77. There was no significant difference in the sensitivity of LR-M between these two standardized algorithms (88.3% of CEUS vs 81.9% of CT/MRI, p = 0.210). Seventy-seven lesions (81.9%) were classified as the same LI-RADS categories by both standardized algorithms (five for LR-5 and 72 for LR-M, kappa value = 0.307). In the subgroup analysis for ICC and CHC, no significant differences were found in the sensitivity of LR-M category between these two standardized algorithms (for ICC, 94.6% of CEUS vs 89.3% of CT/MRI, p = 0.375; for CHC, 76.5% of CEUS vs 70.6% of CT/MRI, p = 0. 649).ConclusionCEUS LI-RADS v2017 and CT/MRI LI-RADS v2018 showed similar value for diagnosing non-HCC primary hepatic malignancies in patients with risks.
In Vivo Characterization of Cortical and White Matter Microstructural Pathology in Growth Hormone-Secreting Pituitary Adenoma
Authors: Yuan Taoyang , Ying Jianyou , Li Chuzhong , Jin Lu , Kang Jie , Shi Yuanyu , Gui Songbai , Liu Chunhui , Wang Rui , Zuo Zhentao , Zhang Yazhuo 
Published: April 2021

BackgroundThe growth hormone (GH) and insulin-like-growth factor 1 (IGF-1) axis has long been recognized for its critical role in brain growth, development. This study was designed to investigate microstructural pathology in the cortex and white matter in growth hormone-secreting pituitary adenoma, which characterized by excessive secretion of GH and IGF-1.Methods29 patients with growth hormone-secreting pituitary adenoma (acromegaly) and 31 patients with non-functional pituitary adenoma as controls were recruited and assessed using neuropsychological test, surface-based morphometry, T1/T2-weighted myelin-sensitive magnetic resonance imaging, neurite orientation dispersion and density imaging, and diffusion tensor imaging.ResultsCompared to controls, we found 1) acromegaly had significantly increased cortical thickness throughout the bilateral cortex (pFDR &lt; 0.05). 2) T1/T2-weighted ratio in the cortex were decreased in the bilateral occipital cortex and pre/postcentral central gyri but increased in the bilateral fusiform, insular, and superior temporal gyri in acromegaly (pFDR &lt; 0.05). 3) T1/T2-weighted ratio were decreased in most bundles, and only a few areas showed increases in acromegaly (pFDR &lt; 0.05). 4) Neurite density index (NDI) was significantly lower throughout the cortex and bundles in acromegaly (pTFCE &lt; 0.05). 5) lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in extensive bundles in acromegaly (pTFCE &lt; 0.05). 6) microstructural pathology in the cortex and white matter were associated with neuropsychological dysfunction in acromegaly.ConclusionsOur findings suggested that long-term persistent and excess serum GH/IGF-1 levels alter the microstructure in the cortex and white matter in acromegaly, which may be responsible for neuropsychological dysfunction.
The Efficacy and Safety of Apatinib Plus Camrelizumab in Patients With Previously Treated Advanced Biliary Tract Cancer: A Prospective Clinical Study
Authors: Wang Dongxu , Yang Xu , Long Junyu , Lin Jianzhen , Mao Jinzhu , Xie Fucun , Wang Yunchao , Wang Yanyu , Xun Ziyu , Bai Yi , Yang Xiaobo , Guan Mei , Pan Jie , Seery Samuel , Sang Xinting , Zhao Haitao 
Published: April 2021

BackgroundPD-1/L1 inhibitor-based immunotherapy is currently under investigation in biliary tract cancer (BTC). Apatinib combined with camrelizumab has achieved promising results in various tumor types. The aim of this study was to assess the safety and efficacy of apatinib plus camrelizumab for advanced biliary tract cancer patients who have received previously treatments.MethodsThis prospective, non-randomized, open-label trial was conducted at Peking Union Medical College Hospital (PUMCH). All included patients received apatinib orally at 250 mg per a day and camrelizumab intravenously at 200 mg every three weeks until disease progression or intolerable toxicity occurred. Efficacy was evaluated based on the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1). Adverse events (AEs) were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0).ResultsA total of 22 patients were consecutively enrolled from 1st December, 2018 until 1st August, 2020. Among 21 patients for whom we could conduct efficacy evaluations, no patients achieved a complete response (CR), 4 patients (19%) achieved partial response (PR), and 11 patients had stable disease with a disease control rate of 71.4%. The median overall survival was 13.1 months (95% CI, 8.1-18.2), and the median progression-free survival was 4.4 months (95% CI, 2.4-6.3). All patients experienced treatment related AEs, and grade 3 or 4 AEs occurred in 14 (63.6%) of 22 patients. No treatment related deaths were observed.ConclusionsThis is the first report focusing on the efficacy and safety of camrelizumab plus apatinib in pretreated biliary tract cancer patients. The finding suggests this regimen has favorable therapeutic effects with relatively manageable toxicity. Further trials with a control arm are required to investigate.Clinical Trial Registrationidentifier NCT04642664.
Time Distributions of Common Respiratory Pathogens Under the Spread of SARS-CoV-2 Among Children in Xiamen, China
Authors: Wang Jinhui , Xiao Tiantian , Xiao Feifan , Hong Shaoxian , Wang Shunqin , Lin Jiancheng , Li Yong , Wang Xiaochuan , Yan Kai , Zhuang Deyi 
Published: April 2021

Objectives: The aim of this study was to observe the effect of COVID-19 prevention and control measures on the transmission of common respiratory viruses in a pediatric population.Methods: This was a retrospective observational study. The study population was selected from children with respiratory diseases who attended Xiamen Children's Hospital from January 1, 2018 to January 31, 2021. All children were screened for influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), adenovirus, and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The changes in respiratory virus detection rates before and after the SARS-CoV-2 intervention were analyzed using an interrupted time-series model. Polynomial curve fitting was also used to predict future short-term trends in respiratory virus detection.Results: A total of 56,859 children were seen at Xiamen Children's Hospital from January 1, 2018 to Jan 31, 2021, of which 32,120 were tested for respiratory viruses via pharyngeal swabs. The overall positive detection rates of the four respiratory viral infections decreased significantly (P = 0.0017) after the implementation of the quarantine and school suspension measures in January 2020. Among them, the detection rate of RSV decreased most significantly (P = 0.008), and although there was no statistically significant difference in the detection rates of the influenza virus, parainfluenza virus, and adenovirus, a downward trend in the graph was observed. The positive detection rates of RSV in the 0–1-, 1–3-, and 3–7-year-old groups all decreased significantly (P = 0.035, 0.016, and 0.038, respectively). The change in the positive detection rate of RSV was relatively stable in the 7–18-year-old group. A total of 10,496 samples were tested for SARS-CoV-2, and no positive cases were reported.Conclusions: The combination of preventive and control measures for COVID-19 reduced the detection rate of four common respiratory viruses, with the greatest impact on RSV. If prevention and control measures continue to be maintained, the overall detection rate or absolute number of detections for the four respiratory viruses will remain low in the short term. However, this trend is likely to vary with the changes in measures.
The Clinical Significance and Potential Role of Cathepsin S in IgA Nephropathy
Authors: Zhao Jingying , Yang Yongchang , Wu Yubin 
Published: April 2021

Objective: Cathepsin S (CTSS) is an important lysosomal cysteine protease. This study aimed at investigating the clinical significance of CTSS and underlying mechanism in immunoglobulin A nephropathy (IgAN).Methods: This study recruited 25 children with IgAN and age-matched controls and their serum CTSS levels were measured by enzyme-linked immunosorbent assay (ELISA). Following induction of IgAN in rats, their kidney CTSS expression, IgA accumulation and serum CTSS were characterized by immunohistochemistry, immunofluorescence, and ELISA. The impact of IgA1 aggregates on the proliferation of human mesangial cells (HMCs) was determined by Cell Counting Kit-8 and Western blot analysis of Ki67.Results: Compared to the non-IgAN controls, significantly up-regulated CTSS expression was detected in the renal tissues, particularly in the glomerular mesangium and tubular epithelial cells of IgAN patients, accompanied by higher levels of serum CTSS (P &lt; 0.05), which were correlated with the levels of 24-h-urine proteins and microalbumin and urine erythrocytes and grades of IgAN Lee's classification in children with IgAN (P &lt; 0.01 for all). Following induction of IgAN, we detected inducible IgA accumulation and increased levels of CTSS expression in the glomerular mesangium and glomerular damages in rats, which were mitigated by LY3000328, a CTSS-specific inhibitor. Treatment with LY3000328 significantly mitigated the Ki67 expression in the kidney of IgAN rats (P &lt; 0.01) and significantly minimized the IgA1 aggregate-stimulated proliferation of HMCs and their Ki67 expression in vitro (P &lt; 0.01).Conclusions: CTSS promoted the proliferation of glomerular mesangial cells, contributing to the pathogenesis of IgAN and may be a new therapeutic target for intervention of aberrant mesangial cell proliferation during the process of IgAN.
RETRACTED: Study on the Effect of Oral Administration of Bacteriophages in Charles Foster Rats With Special Reference to Immunological and Adverse Effects
Authors: Gangwar Mayank , Rastogi Sonam , Singh Digvijay , Shukla Alka , Dhameja Neeraj , Kumar Deepak , Kumar Rajesh , Nath Gopal 
Published: April 2021

Numerous pre-clinical and clinical studies have recently demonstrated the significant role of phage therapy in treating multidrug-resistant bacterial infections. However, only a few researchers have focused on monitoring the phage-mediated adverse reactions during phage therapy. Besides adverse reactions, immunological response after short- and long-term oral administration of bacteriophages is also lacking. In this study, we administered the bacteriophages orally against Klebsiella pneumoniae XDR strain in dosages of 1015 PFU/ml and a 1020 PFU/ml (still higher) to Charles Foster rats as a single dose (in acute toxicity study) and daily dosage for 28 days (in sub-acute toxicity study). One milliliter suspension of bacteriophages was administered through the oral gavage feeding tube. No adverse effect was observed in any of the experimental as well as in the control animals.Further, an insignificant change in food and water intake and body weight was observed throughout the study period compared with the control group rats. On the 28th day of phage administration, blood was collected to estimate hematological, biochemical, and cytokines parameters. The data suggested no difference in the hematological, biochemical, and cytokine profile compared to the control group. No significant change in any of the treatment groups could be observed on the gross and histopathological examinations. The cytokines estimated, interleukin-1 beta (IL-1β), IL-4, IL-6, and INF-gamma, were found within the normal range during the experiment. The results suggested no adverse effect, including the severe detrimental impact on oral administration of high (1015 PFU/ml) and very high dose (1020 PFU/ml) of the bacteriophages cocktail. The high and long-term oral administration of bacteriophages did not induce noticeable immunological response as well.
Patch-Clamp Recordings of Action Potentials From Human Atrial Myocytes: Optimization Through Dynamic Clamp
Authors: Verkerk Arie O. , Marchal Gerard A. , Zegers Jan G. , Kawasaki Makiri , Driessen Antoine H. G. , Remme Carol Ann , de Groot Joris R. , Wilders Ronald 
Published: April 2021

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Consequently, novel therapies are being developed. Ultimately, the impact of compounds on the action potential (AP) needs to be tested in freshly isolated human atrial myocytes. However, the frequent depolarized state of these cells upon isolation seriously hampers reliable AP recordings.Purpose: We assessed whether AP recordings from single human atrial myocytes could be improved by providing these cells with a proper inward rectifier K+ current (IK1), and consequently with a regular, non-depolarized resting membrane potential (RMP), through “dynamic clamp”.Methods: Single myocytes were enzymatically isolated from left atrial appendage tissue obtained from patients with paroxysmal AF undergoing minimally invasive surgical ablation. APs were elicited at 1 Hz and measured using perforated patch-clamp methodology, injecting a synthetic IK1 to generate a regular RMP. The injected IK1 had strong or moderate rectification. For comparison, a regular RMP was forced through injection of a constant outward current. A wide variety of ion channel blockers was tested to assess their modulatory effects on AP characteristics.Results: Without any current injection, RMPs ranged from −9.6 to −86.2 mV in 58 cells. In depolarized cells (RMP positive to −60 mV), RMP could be set at −80 mV using IK1 or constant current injection and APs could be evoked upon stimulation. AP duration differed significantly between current injection methods (p &lt; 0.05) and was shortest with constant current injection and longest with injection of IK1 with strong rectification. With moderate rectification, AP duration at 90% repolarization (APD90) was similar to myocytes with regular non-depolarized RMP, suggesting that a synthetic IK1 with moderate rectification is the most appropriate for human atrial myocytes. Importantly, APs evoked using each injection method were still sensitive to all drugs tested (lidocaine, nifedipine, E-4031, low dose 4-aminopyridine, barium, and apamin), suggesting that the major ionic currents of the atrial cells remained functional. However, certain drug effects were quantitatively dependent on the current injection approach used.Conclusion: Injection of a synthetic IK1 with moderate rectification facilitates detailed AP measurements in human atrial myocytes. Therefore, dynamic clamp represents a promising tool for testing novel antiarrhythmic drugs.
Facing COVID-19 Between Sensory and Psychoemotional Stress, and Instrumental Deprivation: A Qualitative Study of Unmanageable Critical Incidents With Doctors and Nurses in Two Hospitals in Northern Italy
Authors: Testoni Ines , Franco Chiara , Gallo Stampino Enrica , Iacona Erika , Crupi Robert , Pagano Claudio 
Published: April 2021

Background: The COVID-19 pandemic severely strained the already unprepared Italian healthcare system. This had repercussions on healthcare workers, stemming, in particular, from a lack of clear guidelines, adequate protective equipment, and professional preparedness. Such conditions were especially prevalent in Northern Italy.Objectives: This study aimed to examine COVID-19-related professional and psychoemotional stress among nurses and doctors in two hospitals in Northern Italy, along with the worst critical incidents affecting healthcare personnel. A parallel objective was to elicit healthcare professionals' opinions about what changes are needed in the healthcare system's operations, as well as about the relational/emotional skills that are needed to better manage relationships with patients in emergency situations.Participants: Snowball sampling was used to recruit participants and yielded 17 hospital professionals: six nurses (five female and one male) and 11 doctors (seven male and four female). Three of these professionals worked in intensive care and the others in different wards. All had close contact with COVID-19 patients.Methods: The study employed a qualitative research design, using in-depth interviews of ~60 min each that were conducted via Skype video calls. The interviews were recorded and transcribed, then analysed. The qualitative analysis employed mixed methods to identify the most relevant and recursive themes from the interviews.Results: Four fundamental themes emerged from our analysis of the interview texts: (1) disorganisation and psychoemotional stress; (2) urgency and critical incidents; (3) everything surreal; and (4) disruptions in empathetic relationships with patients.Conclusions: Through our analysis of the interview narratives, we found that systematic and in-depth psychological training is needed to prepare professionals for (1) altered relationships with patients in emergencies; (2) use of exceptional medical equipment; (3) elaboration of new bioethical models suitable for disasters and pandemics; and (4) engagement with the themes of death and dying.