bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: a prospective study
Authors: Kobayashi Tomoko , Iwama Shintaro , Yasuda Yoshinori , Okada Norio , Okuji Takayuki , Ito Masaaki , Onoue Takeshi , Goto Motomitsu , Sugiyama Mariko , Tsunekawa Taku , Takagi Hiroshi , Hagiwara Daisuke , Ito Yoshihiro , Suga Hidetaka , Banno Ryoichi , Yokota Kenji , Hase Tetsunari , Morise Masahiro , Hashimoto Naozumi , Ando Masahiko , Fujimoto Yasushi , Hibi Hideharu , Sone Michihiko , Ando Yuichi , Akiyama Masashi , Hasegawa Yoshinori , Arima Hiroshi 
Published: July 2020

BackgroundSeveral immune-related adverse events (irAEs) are reported to be associated with therapeutic efficacy of immune checkpoint inhibitors, yet whether pituitary dysfunction, a life-threatening irAE, affects overall survival (OS) in patients with malignancies is unclear. This prospective study examined the association of pituitary dysfunction (pituitary-irAE) with OS of patients with non-small cell lung carcinoma (NSCLC) or malignant melanoma (MM).MethodsA total of 174 patients (NSCLC, 108; MM, 66) treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab at Nagoya University Hospital were evaluated for OS and the development of pituitary-irAE. Kaplan-Meier curves of OS as a function of the development of pituitary-irAE were produced with the log-rank test as a primary endpoint.ResultsPituitary-irAE was observed in 16 patients (4 (3.7%) with NSCLC, 12 (18.2%) with MM) having two different disease types: hypophysitis with deficiency of multiple anterior pituitary hormones accompanied by pituitary enlargement, and isolated adrenocorticotropic hormone (ACTH) deficiency without pituitary enlargement. Among these patients, 6 developed pituitary-irAE while being treated with ipilimumab (6/25 patients (24.0%) treated with ipilimumab) and 10 developed pituitary-irAE during treatment with nivolumab or pembrolizumab (10/167 (6.0%)). All 16 patients had ACTH deficiency and were treated with physiological doses of hydrocortisone. The development of pituitary-irAE was associated with better OS in patients with NSCLC (not reached vs 441 (95% CI not calculated) days, p<0.05) and MM (885 (95% CI 434 to 1336) vs 298 (95% CI 84 to 512) days, p<0.05).ConclusionsIn our study cohort, the incidence of pituitary-irAE was higher than previously reported and the development of pituitary-irAE predicted better prognosis for both NSCLC and MM when patients were treated with physiological doses of hydrocortisone.Clinical trials registrationUMIN000019024.
Fibrotic Response to Neoadjuvant Therapy Predicts Survival in Pancreatic Cancer and Is Measurable with Collagen-Targeted Molecular MRI
Authors: Erstad Derek J. , Sojoodi Mozhdeh , Taylor Martin S. , Jordan Veronica Clavijo , Farrar Christian T. , Axtell Andrea L. , Rotile Nicholas J. , Jones Chloe , Graham-O'Regan Katherine A. , Ferreira Diego S. , Michelakos Theodoros , Kontos Filippos , Chawla Akhil , Li Shen , Ghoshal Sarani , Chen Yin-Ching Iris , Arora Gunisha , Humblet Valerie , Deshpande Vikram , Qadan Motaz , Bardeesy Nabeel , Ferrone Cristina R. , Lanuti Michael , Tanabe Kenneth K. , Caravan Peter , Fuchs Bryan C. 
Published: July 2020

Abstract

Purpose:
To evaluate the prognostic value of posttreatment fibrosis in human PDAC patients, and to compare a type I collagen targeted MRI probe, CM-101, to the standard contrast agent, Gd-DOTA, for their abilities to identify FOLFIRINOX-induced fibrosis in a murine model of PDAC.

Experimental Design:
Ninety-three chemoradiation-treated human PDAC samples were stained for fibrosis and outcomes evaluated. For imaging, C57BL/6 and FVB mice were orthotopically implanted with PDAC cells and FOLFIRINOX was administered. Mice were imaged with Gd-DOTA and CM-101.

Results:
In humans, post-chemoradiation PDAC tumor fibrosis was associated with longer overall survival (OS) and disease-free survival (DFS) on multivariable analysis (OS P = 0.028, DFS P = 0.047). CPA increased the prognostic accuracy of a multivariable logistic regression model comprised of previously established PDAC risk factors [AUC CPA (−) = 0.76, AUC CPA (+) = 0.82]. In multiple murine orthotopic PDAC models, FOLFIRINOX therapy reduced tumor weight (P &lt; 0.05) and increased tumor fibrosis by collagen staining (P &lt; 0.05). CM-101 MR signal was significantly increased in fibrotic tumor regions. CM-101 signal retention was also increased in the more fibrotic FOLFIRINOX-treated tumors compared with untreated controls (P = 0.027), consistent with selective probe binding to collagen. No treatment-related differences were observed with Gd-DOTA imaging.

Conclusions:
In humans, post-chemoradiation tumor fibrosis is associated with OS and DFS. In mice, our MR findings indicate that translation of collagen molecular MRI with CM-101 to humans might provide a novel imaging technique to monitor fibrotic response to therapy to assist with prognostication and disease management.
A Biomarker-enriched, Randomized Phase II Trial of Adavosertib (AZD1775) Plus Paclitaxel and Carboplatin for Women with Platinum-sensitive TP53-mutant Ovarian Cancer
Authors: Oza Amit M. , Estevez-Diz Maria , Grischke Eva-Maria , Hall Marcia , Marmé Frederik , Provencher Diane , Uyar Denise , Weberpals Johanne I. , Wenham Robert M. , Laing Naomi , Tracy Michael , Freshwater Tomoko , Lee Mark A. , Liu Ji , Qiu Jingjun , Rose Shelonitda , Rubin Eric H. , Moore Kathleen 
Published: July 2020

Abstract

Purpose:
Preclinical studies show that adavosertib, a WEE1 kinase inhibitor, sensitizes TP53-mutant cells to chemotherapy. We hypothesized that adavosertib, plus chemotherapy, would enhance efficacy versus placebo in TP53-mutated ovarian cancer.

Patients and Methods:
Following safety run-in, this double-blind phase II trial (NCT01357161) randomized women with TP53-mutated, platinum-sensitive ovarian cancer to oral adavosertib (225 mg twice daily for 2.5 days/21-day cycle) or placebo, plus carboplatin (AUC5) and paclitaxel (175 mg/m2), until disease progression or for six cycles. The primary endpoints were progression-free survival (PFS) by enhanced RECIST v1.1 [ePFS (volumetric)] and safety. Secondary/exploratory objectives included PFS by RECIST v1.1 (single dimension), objective response rate, overall survival, and analysis of tumor gene profile versus sensitivity to adavosertib.

Results:
A total of 121 patients were randomized to adavosertib (A+C; n = 59) and placebo (P+C; n = 62) plus chemotherapy. Adding adavosertib to chemotherapy improved ePFS [median, 7.9 (95% confidence interval (CI), 6.9–9.9) vs. 7.3 months (5.6–8.2); HR 0.63 (95% CI, 0.38–1.06); two-sided P = 0.080], meeting the predefined significance threshold (P &lt; 0.2). Clinical benefit was observed following A+C for patients with different TP53 mutation subtypes, identifying possible response biomarkers. An increase in adverse events was seen with A+C versus P+C: greatest for diarrhea (adavosertib 75%; placebo 37%), vomiting (63%; 27%), anemia (53%; 32%), and all grade ≥3 adverse events (78%; 65%).

Conclusions:
Establishing an optimal strategy for managing tolerability and identifying specific patient populations most likely to benefit from treatment may increase clinical benefit. Future studies should consider additional adavosertib doses within the chemotherapy treatment cycle and the potential for maintenance therapy.
The Gut Microbiota Impact Cancer Etiology through “Phase IV Metabolism” of Xenobiotics and Endobiotics
Authors: Ervin Samantha M. , Redinbo Matthew R. 
Published: July 2020

Abstract
The human gut microbiome intimately complements the human genome and gut microbial factors directly influence health and disease. Here we outline how the gut microbiota uniquely contributes to cancer etiology by processing products of human drug and endobiotic metabolism. We formally propose that the reactions performed by the gut microbiota should be classified as “Phase IV xenobiotic and endobiotic metabolism.” Finally, we discuss new data on the control of cancer by the inhibition of gut microbial phase IV enzymes responsible for tumor initiation and progression.
Utility of Human-Derived Models for Glioblastoma
Authors: Luo Xujun , Weiss William A. 
Published: July 2020

Abstract

Summary:
In this issue, Pine and colleagues compared single-cell RNA-sequencing data across four distinct types of glioblastoma stem cell–derived tumor models, reinforcing the importance of a three-dimensional microenvironment for accurate recapitulation of cellular states.
See related article by Pine et al., p. 964.
O passado da língua no cinema: um estudo diacrônico do pretérito perfecto na variedade bonaerense
Authors: Araujo Leandro Silveira de , Coradi Laura De Oliveira 
Published: July 2020

A carência de pesquisas centradas no estudo diacrônico do espanhol portenho e sobre a história dos usos do pretérito perfecto simple(PPS) e pretérito perfecto compuesto(PPC) na Argentina salientam a relevância deste estudo. A partir da comparação de filmes argentinos de dois momentos históricos, separados por um intervalo aproximado de sessenta anos – (a) 1958 (Rosaura a las diez) e (b) 2013 (Corazón de León) – observamos o uso do PPS e PPC e quais fatores poderiam estar por detrás de sua variação. A seguinte pergunta auxiliou o desenvolvimento da pesquisa: Qual é a diferença no uso do PPS e PPC nos dois cronoletos analisados? Verificamos que, apesar da predominância do uso da forma simples, a forma composta não está excluída do uso no espanhol argentino. Ademais, as duas formas assumem valores distintos dos entoados por manuais prescritivos da Língua Espanhola, ou seja, além do valor de passado absoluto, nota-se o uso do PPS com valor de antepresente. Igualmente, o PPC ocorreu no passado, com valor de passado absoluto, para além do uso com valor de antepresente.
Los conectores contraargumentativos y la enseñanza de español como lengua adicional
Authors: Esteve Cristina Corral 
Published: July 2020

La enseñanza de los marcadores discursivos en las clases de español en Brasil continúa siendo un problema a pesar de todos los estudios realizados en las últimas décadas. El propósito de este trabajo es aportar un poco de luz a fin de construir un puente entre la teoría y la práctica. Nuestro objetivo es presentar herramientas que nos permitan conocer más el grupo de los conectores contraargumentativos a partir de la propuesta de Garrido Rodríguez (2004), que los considera marcas de coherencia textual, señales de progresión argumentativa del discurso y guías para la interpretación del enunciado. Comenzaremos presentando los marcadores discursivos en general y los conectores contraargumentativos en particular a partir de la reflexión sobre sus características formales, las instrucciones semánticas que presentan y sus efectos contextuales (Martín Zorraquino y Portolés, 1999). Luego, hacemos una breve revisión bibliográfica de las principales investigaciones realizadas sobre el español. Finalmente, presentamos una tabla de cada conector del grupo de los contraargumentativos.
Thoracic cancer surgery during the COVID-19 pandemic: a consensus statement from the Thoracic Domain of the Asian Society for Cardiovascular and Thoracic Surgery
Authors: Jheon Sanghoon , Ahmed Aneez DB , Fang Vincent WT , Jung Woohyun , Khan Ali Zamir , Lee Jang-Ming , Sihoe Alan DL , Thongcharoen Punnarerk , Tsuboi Masahiro , Turna Akif , Nakajima Jun 
Published: July 2020

Objectives Healthcare resources have been mobilized to combat the COVID-19 pandemic of 2020. The Thoracic Domain of the Asian Society for Cardiovascular and Thoracic Surgery reports a consensus statement on the provision of thoracic cancer surgery during this pandemic. Methods A Thoracic Experts Panel was convened by the Society. A consensus on the provision, safety, and setting of thoracic cancer surgery during the pandemic was obtained through a Delphi process. Results Responses were received from 26 panel members (96% response rate) from 10 regions across Asia. The Society recommended that elective thoracic cancer surgery services may need to be reduced or postponed if medical resources were needed for COVID-19 patients, especially intensive care unit beds and ventilators. However, thoracic cancer surgery should proceed as normal for all solid tumors, without restrictions based on disease stage, availability of non-surgical treatment options, or patient condition (unless there is a high likelihood of postoperative intensive care unit stay). Aerosol-forming procedures should be avoided intra- and perioperatively. The surgical approach does not make a difference in terms of safety. Services for thoracic cancer patients should be offered only in hospitals that maintain isolation wards for patients with confirmed or suspected COVID-19. Conclusions Services for patients with thoracic cancer should be maintained during the COVID-19 pandemic. The position of the Society is that thoracic surgeons have a responsibility to perform good surgical management of thoracic cancer during the pandemic, to advocate for patients’ rights to receive it, and to safeguard patients and staff from infection.
Epidemiology of fatal/non-fatal suicide among patients with chronic osteomyelitis (COM): a nationwide population-based study
Authors: Hung Chih-Hung , Ko Jih-Yang , Liao Pei-Shao , Yeh Chen-Wei , Hsu Chieh-Cheng , Lin Mei-Chen , Hsu Horng-Chaung , Kuo Shu-Jui 
Published: July 2020

Objective Chronic osteomyelitis (COM) can induce systemic inflammation, and systemic inflammation may be associated with suicide tendency. However, no studies have investigated the correlation between COM and suicide tendency. Methods The aim of this population-based study was to determine the epidemiology of fatal/non-fatal suicide among COM patients. Subjects with at least two outpatient visits or one course of inpatient care diagnosed with COM were recruited into a COM cohort. The control/COM subject ratio was approximately 4:1 matched by age, sex, major depression coding and index year (COM patients). Subjects with suicide attempts before COM diagnosis and subjects aged <20 years were excluded. Results COM patients had 1.93 (95% confidence interval [CI]: 1.11–3.36) times the risk of fatal/non-fatal suicide as control subjects. Considering death as the competing event of fatal/non-fatal suicide, COM patients had 1.76 (95% CI: 1.03–3.01) times the risk of fatal/non-fatal suicide (competing risk regression model). The effect of COM on fatal/non-fatal suicide was more prominent among diabetic patients. COM severity also correlated with the risk of fatal/non-fatal suicide. Conclusions More attention must be paid to suicide tendency among COM patients.
Stability analysis of glass fibre polyamide composite transmission tower
Authors: Bhowmik Chiranjit , Gupta Krishanu , Chakraborti Prasun 
Published: July 2020

The cross-sectional degradation of steel transmission tower members due to corrosion has been one of the major issues in the transmission line system. The degradation of appearance of the material has also been seen because of corrosion. Therefore, there is a need for a less corrosive and high strength alternate material for transmission towers. It seems in recent years that alternate materials have been needed to replace steel which have low maintenance cost and good resistance to corrosion. The advantages of composite transmission towers are fire resistant, high stiffness, durability, high strength, moderate ductility, rigidity, easy to assemble and economical. The present study has made an effort to evaluate the performance of composite transmission tower. The glass fibre polyamide composite material has been used as a structural material. First, a finite element tower model of 132 KV has been set up in Structural Analysis and Design Software as glass fibre polyamide structural material as per transmission tower design guidelines (Code for Transmission tower design, IS 802.1.1.1995, Bureau of Indian Standards). Second, all the active loads like wind load on the body, wind load on conducting wires and ground wires, weight of conducting wires, weight of structure, weight of ground wires, weight of insulator and weight of line man with tools are calculated manually as per transmission tower design guidelines and applied in the finite element tower model. The stress distribution of the composite tower model has been simulated in Structural Analysis and Design Software and the results have been analysed. The broken wire condition (if one conductor is broken or earth wire is broken) has been innovatively considered in the present study. Results obtained in this article show that maximum induced stress on transmission tower member is less than the deign strength of glass fibre polyamide composite material. The glass fibre polyamide composite material has been found to be capable to withstand the maximum stresses induced due to different loading conditions considered in the study.
Clinical characterization, outcomes, and prognosis in patients with systemic lupus erythematosus admitted to the intensive care unit
Authors: Aragón Cristian C , Ruiz-Ordoñez Ingrid , Quintana Jhon H , Suárez-Avellaneda Ana , Gallego Linda M , Gallego Cindy-Natalia , Bolaños Juan D , Guerra María A , Ochoa Maria Elena , Granados Marcela , Tobón Gabriel J 
Published: July 2020

Objective Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease, and in some conditions, admission to the intensive care unit (ICUs) is required. This study describes the clinical and prognostic factors in SLE patients admitted to the ICU. Methods We conducted a retrospective study that reviewed all clinical records of patients with SLE admitted to the ICU between 2011 and 2018. Results We evaluated 188 patients, with 279 ICU admissions. Most patients were female ( n = 159; 84.57%) with a median age of 35 years (interquartile range (IQR) = 25–48 years). Infection was the leading cause of admission in 77 (27.60%) cases, followed by lupus flare. The average length of hospitalization was 5 days (IQR 3–11 days), and the SLE Disease Activity Index 2000, Acute Physiology, Age and Chronic Health Evaluation (APACHE II), and Sequential Organ Failure Assessment (SOFA) scores were 9 (IQR 2–17), 14 (IQR 10–17), and 3 (IQR 2–5), respectively. Non-survivors presented with higher APACHE II and SOFA scores. Infection was the leading cause of mortality ( n = 38; 20.21%), and predictors of mortality included invasive mechanical ventilation, vasoactive medication requirement, higher SOFA scores, and antiphospholipid syndrome comorbidity. Conclusions We found that infection was the leading cause of ICU admissions and mortality in patients with SLE. Factors identified here as predictors of mortality should be accurately identified at admission for the prompt treatment of SLE patients.
Clinical features, damage accrual, and survival in patients with familial systemic lupus erythematosus: data from a multi-ethnic, multinational Latin American lupus cohort
Authors: Quintana Rosana , Pons-Estel Guillermo J , Roberts Karen , Sacnún Mónica , Serrano Rosa , Nieto Romina , Conti Silvana , Gervasoni Viviana , Catoggio Luis J , Soriano Enrique R , Scolnik Marina , García Mercedes A , Alvarellos Alejandro , Saurit Verónica , Berbotto Guillermo A , Sato Emilia I , Costallat Lilian T Lavras , Neto Eduardo Ferreira Borba , Bonfa Eloisa , Xavier Ricardo M , de Oliveira e Silva Montandon Ana Carolina , Molina-Restrepo José Fernando , Iglesias-Gamarra Antonio , Guibert-Toledano Marlene , Reyes-Llerena Gil Alberto , Massardo Loreto , Neira Oscar J , Cardiel Mario H , Barile-Fabris Leonor A , Amigo Mary-Carmen , Silveira Luis H , Torre Ignacio García De La , Acevedo-Vásquez Eduardo M , Ugarte-Gil Manuel F , Alfaro-Lozano José Luis , Segami María Inés , Chacón-Díaz Rosa , Esteva-Spinetti María H , Gomez-Puerta José A , Alarcón Graciela S , Pons-Estel Bernardo A 
Published: July 2020

Objectives This study aimed to compare the clinical features, damage accrual, and survival of patients with familial and sporadic systemic lupus erythematosus (SLE). Methods A multi-ethnic, multinational Latin American SLE cohort was studied. Familial lupus was defined as patients with a first-degree SLE relative; these relatives were interviewed in person or by telephone. Clinical variables, disease activity, damage, and mortality were compared. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. Hazard ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for time to damage and mortality. Results A total of 66 (5.6%) patients had familial lupus, and 1110 (94.4%) had sporadic lupus. Both groups were predominantly female, of comparable age, and of similar ethnic distribution. Discoid lupus (OR = 1.97; 95% CI 1.08–3.60) and neurologic disorder (OR = 1.65; 95% CI 1.00–2.73) were significantly associated with familial SLE; pericarditis was negatively associated (OR = 0.35; 95% CI 0.14–0.87). The SLE Disease Activity Index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) were similar in both groups, although the neuropsychiatric (45.4% vs. 33.5%; p = 0.04) and musculoskeletal (6.1% vs. 1.9%; p = 0.02) domains of the SDI were more frequent in familial lupus. They were not retained in the Cox models (by domains). Familial lupus was not significantly associated with damage accrual (HR = 0.69; 95% CI 0.30–1.55) or mortality (HR = 1.23; 95% CI 0.26–4.81). Conclusion Familial SLE is not characterized by a more severe form of disease than sporadic lupus. We also observed that familial SLE has a higher frequency of discoid lupus and neurologic manifestations and a lower frequency of pericarditis.
Insulin resistance and serum levels of adipokines in patients with systemic lupus erythematosus: a systematic review and meta-analysis
Authors: Kuo Che-Yuan , Tsai Tsung-Yu , Huang Yu-Chen 
Published: July 2020

Background We aimed to perform a systematic review and meta-analysis of studies assessing the homeostasis model assessment for insulin resistance (HOMA-IR) values, serum adiponectin, leptin and resistin levels in patients with systemic lupus erythematosus (SLE). Method Online databases were searched on 31 March 2019 in order to identify studies comparing HOMA-IR, serum adiponectin, leptin and resistin levels between patients with SLE and controls. A random-effects model was adopted. Results Fifty-six studies involving a total of 4460 patients with SLE were included. Patients with SLE had significantly higher HOMA-IR values (standardized mean difference (SMD)=0.425; 95% confidence interval (CI) 0.156–0.693; I2=93.8%) than the control group. The serum levels of adiponectin (SMD=0.547; 95% CI 0.219–0.874; I2=90.1%), leptin (SMD=0.843; 95% CI 0.454–1.231; I2=94.4%) and resistin (SMD=0.856; 95% CI 0.199–1.513; I2=96.6%) were all higher among patients with SLE than controls. A meta-regression analysis revealed that the serum resistin level was positively correlated with disease activity (coefficient 0.123; 95% CI 0.051–0.195; p<0.001). Conclusion Patients with SLE have higher HOMA-IR values and serum levels of adiponectin, leptin and resistin than individuals without SLE. The serum level of resistin correlates with SLE disease activity.