bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of oral metronomic etoposide in adult patients with metastatic osteosarcoma
Authors: Perret Audrey , Dômont Julien , Chamseddine Ali N. , Dumont Sarah N. , Verret Benjamin , Briand Sylvain , Court Charles , Lazure Thierry , Adam Julien , Ngo Carine , Even Caroline , Levy Antonin , Bayle Arnaud , Lucibello Francesca , Haddag‐Miliani Leila , Faron Matthieu , Honoré Charles , Le Cesne Axel , Mir Olivier
Published: November 2020

Therapeutic options in patients with metastatic osteosarcoma are limited and effective systemic treatments are needed in this setting. The aim of this case series was to assess the efficacy and toxicity of oral metronomic etoposide in adult patients with progressive metastatic osteosarcoma. We retrospectively reviewed the electronic records of patients treated with oral metronomic etoposide (25 mg thrice daily, 3 weeks out of 4) from December 2002 to December 2018 at Gustave Roussy (Villejuif, France). The primary endpoint was progression‐free rate (PFR) at 4 months; secondary endpoints were: best response (according to RECIST v1.1), progression‐free survival (PFS), overall survival (OS) and safety. With a median follow‐up of 9.8 months, 37 patients were eligible for this analysis: 68% males, median age 42 (range: 21–75), 19% with synchronous metastases, 92% with lung metastases, median PS: 1 (range: 0–3). Median number of previous treatment lines in the metastatic setting was 1 (range: 0–4). Progression‐free rate at 4 months was 40.3% (95% CI: 24.5–56.2). Best response was partial response in 11% and stable disease in 35% of patients (disease control rate: 46%). Median PFS was 3.1 months (95% CI: 2.5–4.7) and median OS was 9.8 months (95% CI: 5.1–12.3). Toxicity profile was acceptable, with 13% grade 3 haematological toxicities (anaemia and neutropenia), without any grade 3–4 non‐haematological toxicity. In our experience, oral metronomic etoposide demonstrated effective palliation along with acceptable toxicity in patients with progressive metastatic osteosarcoma.
New Pyrano‐4H‐benzo[g]chromene‐5,10‐diones with Antiparasitic and Antioxidant Activities
Authors: Al Nasr Ibrahim S. , Jentzsch Jana , Shaikh Amin , Singh Shuveksh Priti , Koko Waleed S. , Khan Tariq A. , Ahmed Khursheed , Schobert Rainer , Ersfeld Klaus , Biersack Bernhard
Published: November 2020

New pyranonaphthoquinone derivatives were synthesized and investigated for their activity against Trypanosoma brucei, Leishmania major, and Toxoplasma gondii parasites. The pentafluorophenyl derivative was efficacious against T. brucei with single digit micromolar EC50 values and against T. gondii with even sub‐micromolar values. The 3‐chloro‐4,5‐dimethoxyphenyl derivative showed an activity against amastigotes of Leishmania major parasites comparable to that of amphotericin B. In addition, antioxidant activities were observed for the bromophenyl derivatives, and their redox behavior was studied by cyclovoltammetry. Anti‐parasitic and antioxidative activities of the new naphthoquinone derivatives appear uncorrelated.
Synthetic Application of Cyclodextrins in Combination with Metal Ions, Complexes, and Metal Particles
Authors: Molnár Árpád
Published: November 2020

Cyclodextrins are green, environmentally benign products available through the enzymatic degradation of starch for a multitude of varied applications. This review attempts to collect useful information with respect to catalytic studies performed with the use of cyclodextrin and modified cyclodextrin preparations applied in combination of or loaded with varied catalytically active species including metal ions, complexes, and metal particles. Major sections are about their use in hydrogenation, reduction, oxidation, hydroformylation and coupling reactions. Additional sections include their utilization in ring formation and ring opening as well as degradation of pollutants. In the last part, examples about ester hydrolysis, hydroboration and hydrosilylation, as well as hydrogen production are treated. Data collected and analyzed indicate the importance and high potential of cyclodextrin‐based catalysts in sustainable chemistry.
Bifunctional α‐MnO2 and Co3O4 Catalyst for Oxygen Electrocatalysis in Alkaline Solution
Authors: Fink Michael F. , Eckhardt Julia , Khadke Prashant , Gerdes Thorsten , Roth Christina
Published: November 2020

Low cost and abundant catalysts demonstrating high activity and stability towards the oxygen reactions, i. e., the oxygen reduction (ORR) and oxygen evolution reaction (OER), are crucial for the development of electrically rechargeable zinc‐air batteries. Herein, the facile synthesis and systematic characterisation of two highly active and stable oxygen electrocatalysts, i. e., high surface area α‐MnO2 microspheres and nanoparticulate Co3O4, are reported. α‐MnO2 exhibits low half‐wave potential and potential of −0.197 and −0.226 V (vs. Ag/AgCl) at −3 mA cm−2, respectively, that are only marginally higher compared to commercial Pt/C (E1/2=−0.161 V, Ej=‐3=−0.171 V) for ORR. Meanwhile, Co3O4 needs a potential of 0.601 V (vs. Ag/AgCl) to drive 10 mA cm−2 being competitive to commercial Ir/C (Ej=10=0.60 V) for OER. In order to create a bifunctional catalyst, two approaches were pursued: i) Co3O4 nanoparticles were homogeneously grown on the surface of α‐MnO2 microspheres yielding a radial hybrid composite catalyst material in the form of a core (α‐MnO2) shell (Co3O4) structure and ii), much simpler, individual α‐MnO2 microspheres and Co3O4 nanoparticles were physically mixed in a powder blend. The powder blend demonstrates superior overall bifunctional catalytic properties such that the individual catalysts still dominate their respective oxygen reaction and, due to synergistic interactions between both catalysts, an improved ORR activity could be achieved.
A randomized, open‐label, phase 2, multicenter trial of gemcitabine with pazopanib or gemcitabine with docetaxel in patients with advanced soft‐tissue sarcoma
Authors: Somaiah Neeta , Van Tine Brian Andrew , Wahlquist Amy E. , Milhem Mohammed M. , Hill Elizabeth G. , Garrett‐Mayer Elizabeth , Armeson Kent E. , Schuetze Scott M. , Meyer Christian F. , Reuben Daniel Y. , Elias Anthony D. , Read William L. , Chawla Sant P. , Kraft Andrew S.
Published: November 2020

Background

Therapeutic options for patients with advanced soft‐tissue sarcoma (STS) are limited. The goal of the current phase 2 study was to examine the clinical activity and safety of the combination of gemcitabine plus pazopanib, a multityrosine kinase inhibitor with activity in STS.

Methods

The current randomized, phase 2 trial enrolled patients with advanced nonadipocytic STS who had received prior anthracycline‐based therapy. Patients were assigned 1:1 to receive gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 with pazopanib at a dose of 800 mg daily (G+P) or gemcitabine at a dose of 900 mg/m2 on days 1 and 8 and docetaxel at a dose of 100 mg/m2 on day 8 (G+T) every 3 weeks. Crossover was allowed at the time of disease progression. The study used a noncomparative statistical design based on the precision of 95% confidence intervals for reporting the primary endpoints of median progression‐free survival (PFS) and rate of grade ≥3 adverse events (AEs) for these 2 regimens based on the intent‐to‐treat patient population (AEs were graded using version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events).

Results

A total of 90 patients were enrolled: 45 patients on each treatment arm. The median PFS was 4.1 months for each arm (P = .3, log‐rank test). The best overall response of stable disease or better (complete response + partial response + stable disease) was the same for both treatment arms (64% for both the G+T and G+P arms). The rate of related grade ≥3 AEs was 82% for the G+T arm and 78% for the G+P arm. Related grade ≥3 AEs occurring in ≥10% of patients in the G+T and G+P arms were anemia (36% and 20%, respectively), fatigue (29% and 13%, respectively), thrombocytopenia (53% and 49%, respectively), neutropenia (20% and 49%, respectively), lymphopenia (13% and 11%, respectively), and hypertension (2% and 20%, respectively).

Conclusions

The data from the current study have demonstrated the safety and efficacy of G+P as an alternative to G+T for patients with nonadipocytic STS.
Results from a prospective longitudinal survey of employment and work outcomes in newly diagnosed cancer patients during and after curative‐intent chemotherapy: A Wisconsin Oncology Network study
Authors: Tevaarwerk Amye J. , Kwekkeboom Kris , Buhr Kevin A. , Dennee Alexandra , Conkright William , Onitilo Adedayo A. , Robinson Emily , Ahuja Harish , Kwong Roger W. , Nanad Ranveer , Wiegmann Douglas A. , Chen Karen , LoConte Noelle K. , Wisinski Kari B. , Sesto Mary E.
Published: November 2020

Background

Postcancer work limitations may affect a substantial proportion of patients and contribute to the “financial toxicity” of cancer treatment. The degree and nature of work limitations and employment outcomes are poorly understood for cancer patients, particularly in the immediate period of transition after active treatment. We prospectively examined employment, work ability, and work limitations during and after treatment.

Methods

A total of 120 patients receiving curative therapy who were employed prior to their cancer diagnosis and who intended to work during or after end of treatment (EOT) completed surveys at baseline (pretreatment), EOT, and 3, 6, and 12 months after EOT. Surveys included measures of employment, work ability, and work limitations. Descriptive statistics (frequencies, percentages, means with standard deviations) were calculated.

Results

A total of 111 participants completed the baseline survey. On average, participants were 48 years of age and were mostly white (95%) and female (82%) with a diagnosis of breast cancer (69%). Full‐time employment decreased during therapy (from 88% to 50%) and returned to near prediagnosis levels by 12‐month follow‐up (78%). Work‐related productivity loss due to health was high during treatment.

Conclusions

This study is the first to report the effects of curative intent cancer therapy on employment, work ability, and work limitations both during and after treatment. Perceived work ability was generally high overall 12 months after EOT, although a minority reported persistent difficulty. A prospective analysis of factors (eg, job type, education, symptoms) most associated with work limitations is underway to assist in identifying at‐risk patients.
Efficacy of inotuzumab ozogamicin in patients with Philadelphia chromosome–positive relapsed/refractory acute lymphoblastic leukemia
Authors: Stock Wendy , Martinelli Giovanni , Stelljes Matthias , DeAngelo Daniel J. , Gökbuget Nicola , Advani Anjali S. , O’Brien Susan , Liedtke Michaela , Merchant Akil A. , Cassaday Ryan D. , Wang Tao , Zhang Hui , Vandendries Erik , Jabbour Elias , Marks David I. , Kantarjian Hagop M.
Published: November 2020

Background

Patients with relapsed/refractory (R/R) Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) have a poor prognosis and limited treatment options.

Methods

The efficacy of inotuzumab ozogamicin (InO), a humanized anti‐CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, was evaluated in R/R ALL patients in the phase 1/2 study 1010 (NCT01363297) and open‐label, randomized, phase 3 study 1022 (INO‐VATE; NCT01564784). This analysis focused specifically on Ph+ R/R ALL patients. In study 1022, Ph+ patients were randomly assigned 1:1 to InO (n = 22) or standard intensive chemotherapy (SC) (n = 27) and 16 Ph+ patients in study 1010 received InO.

Results

In study 1022, rates of complete remission/complete remission with incomplete hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity (patients achieving CR/CRi) were higher with InO (CR/CRi = 73%; MRD = 81%) versus SC (CR/CRi = 56%; MRD = 33%). The corresponding rates in study 1010 were 56% (CR/CRi) and 100% (MRD). The hematopoietic stem cell transplantation (HSCT) rate in study 1022 was 41% versus 19% for InO versus SC; however, there was no benefit in overall survival (median OS: 8.7 vs 8.4 months; hazard ratio, 1.17 [95% CI, 0.64‐2.14]). The probability of being event‐free (progression‐free survival) at 12 months was greater with InO versus SC (20.1% vs 4.8%).

Conclusion

Given the substantial improvement in responses and rates of HSCT, InO is an important treatment option for patients with R/R Ph+ ALL. Future studies need to consider better characterization of disease characteristics, more sensitive MRD measurements, MRD‐directed therapy before HSCT, and potentially combination therapies, including tyrosine kinase inhibitors.
Health‐related quality of life outcomes among breast cancer survivors
Authors: Park Jihye , Rodriguez Juan L. , O’Brien Katie M. , Nichols Hazel B. , Hodgson M. Elizabeth , Weinberg Clarice R. , Sandler Dale P.
Published: November 2020

Background

Data from a nationwide sample of US breast cancer survivors were used to examine associations between patient characteristics (breast cancer clinical features, prognostic factors, and treatments) and health‐related quality of life (HRQOL). Associations between postdiagnosis HRQOL and mortality were then evaluated.

Methods

The authors identified female breast cancer survivors (n = 2453) from the Sister Study or Two Sister Study who were at least 1 year from breast cancer diagnosis and who had responded to a survivorship survey in 2012. HRQOL was assessed with the Patient‐Reported Outcomes Measurement Information System (PROMIS) Global 10 measures. Multivariable linear regression was used to assess predictors associated with HRQOL. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HRQOL and all‐cause mortality.

Results

HRQOL, assessed an average of 4.9 years after the cancer diagnosis (standard deviation of 1.9 years), was negatively associated with a higher cancer stage at diagnosis; a higher comorbidity score at the survey; experience of surgical complications; dissatisfaction with breast surgery; and experience of any recent recurrence, metastasis, or secondary malignancy. Since the completion of the survey, there were 85 deaths (3.5%) during a mean follow‐up of 4 years (standard deviation of 0.5 years). In multivariate models, decreases in PROMIS physical T scores and mental T scores were associated with increased mortality (HR for physical T scores, 1.08; 95% CI, 1.05‐1.11; HR for mental T scores, 1.03; 95% CI, 1.01‐1.06).

Conclusions

Prognostic and cancer treatment–related factors affect HRQOL in breast cancer survivors and may inform targeted survivorship care. PROMIS global health measures may offer additional insights into patients' well‐being and mortality risk.

Lay Summary

Findings from a study suggest that prognostic and cancer treatment–related factors affect health‐related quality of life (HRQOL) in breast cancer survivors and that poor HRQOL may increase the mortality risk.

The evaluation of HRQOL is important because it may hold potential as a tool for optimizing survivorship care.
Thyroid paraganglioma: A diagnostic pitfall in thyroid FNA
Authors: Satturwar Swati P. , Rossi Esther D. , Maleki Zahra , Cantley Richard L. , Faquin William C. , Pantanowitz Liron
Published: November 2020

Background

Thyroid paragangliomas are extremely rare and often are misdiagnosed by preoperative fine‐needle aspiration (FNA) because their cytologic features overlap with those of other thyroid neoplasms. The objective of this study was to review the cytomorphology in a series of thyroid paragangliomas and correlate the findings with histopathology.

Methods

Five thyroid paraganglioma cases that underwent FNA were reviewed. Their clinical presentation, radiology features, cytomorphology, ancillary tests, and histopathology were analyzed.

Results

All patients were women with an average age of 49 years (age range, 35‐61 years) and presented with an asymptomatic, solitary thyroid nodule. Radiologically, these nodules (size range, 1.8‐3.0 cm) were well circumscribed, hypoechoic, and hypervascular. FNA smears showed clusters of loosely cohesive, medium‐to‐large epithelioid cells with clear‐to‐eosinophilic and occasionally foamy cytoplasm that had indistinct cytoplasmic borders. The nuclei were round to oval with focal nuclear membrane irregularities, inconspicuous nucleoli, focal marked anisonucleosis, and occasional intranuclear pseudoinclusions. Naked nuclei, variable numbers of plasmacytoid cells, multinucleated giant cells, and sustentacular cells were present in the background along with blood vessels and lymphocytes. Cytology diagnoses were incorrect and included follicular neoplasm (n = 4) and follicular lesion of undetermined significance (n = 1). Final histopathology with immunohistochemistry revealed conventional paraganglioma (n = 3) or sclerosing paraganglioma with invasive features (n = 2).

Conclusions

All thyroid paragangliomas were misdiagnosed on FNA as follicular neoplasms, in part because of the rarity of these tumors in this location and cytomorphology mimicking follicles. The absence of colloid, the presence of naked nuclei, focal marked anisonucleosis, and the presence of sustentacular cells are important cytology clues.
Cell type‐ and layer‐specific convergence in core and shell neurons of the dorsal lateral geniculate nucleus
Authors: Okigawa Sayumi , Yamaguchi Masahiro , Ito Kei N. , Takeuchi Ryosuke F. , Morimoto Nao , Osakada Fumitaka
Published: November 2020

Over 40 distinct types of retinal ganglion cells (RGCs) generate parallel processing pathways in the visual system. In mice, two subdivisions of the dorsal lateral geniculate nucleus (dLGN), the core and the shell, organize distinct parallel channels to transmit visual information from the retina to the primary visual cortex (V1). To investigate how the dLGN core and shell differentially integrate visual information and other modalities, we mapped synaptic input sources to each dLGN subdivision at the cell‐type level with G‐deleted rabies viral vectors. The monosynaptic circuit tracing revealed that dLGN core neurons received inputs from alpha‐RGCs, Layer 6 neurons of the V1, the superficial and intermediate layers of the superior colliculus (SC), the internal ventral LGN, the lower layer of the external ventral LGN (vLGNe), the intergeniculate leaf, the thalamic reticular nucleus (TRN), and the pretectal nucleus (PT). Conversely, shell neurons received inputs from alpha‐RGCs and direction‐selective ganglion cells of the retina, Layer 6 neurons of the V1, the superficial layer of the SC, the superficial and lower layers of the vLGNe, the TRN, the PT, and the parabigeminal nucleus. The present study provides anatomical evidence of the cell type‐ and layer‐specific convergence in dLGN core and shell neurons. These findings suggest that dLGN core neurons integrate and process more multimodal information along with visual information than shell neurons and that LGN core and shell neurons integrate different types of information, send their own convergent information to discrete populations of the V1, and differentially contribute to visual perception and behavior.
Exploring a system architecture of content‐based publish/subscribe system for efficient on‐the‐fly data dissemination
Authors: Yoon Daegun , Park Gyudong , Oh Sangyoon
Published: November 2020

In a cloud‐scale publish/subscribe messaging system, it is difficult to partition subscription data among several servers. Without a sophisticated scheme and a system architecture, the messaging system would either waste resources or fail to deliver messages on time. In this study, we propose DRDA, a dynamic replication degree adjustment technology, for efficient message delivery. The technology calculates and maintains the number of subscription replications at a reasonable level by monitoring the statuses of servers, based on the number of subscription replications and the frequency of event dissemination. To verify the effectiveness of our proposed scheme and system architecture, we build a prototype of a content‐based publish/subscribe system that dynamically adjusts the number of replications among brokers. Furthermore, we compare the load balance, resource overhead, and performance of a publish/subscribe system with DRDA with a publish/subscribe system without DRDA. The experimental results show that DRDA outperforms other approaches under various parameter configurations. We have added the prototype code to a GitHub repository to make it publicly available.
Time‐to‐detection occupancy methods: performance and utility for improving efficiency of surveys
Authors: Halstead Brian J. , Rose Jonathan P. , Kleeman Patrick M.
Published: November 2020

Occupancy methods propelled the quantitative study of species distributions forward by separating the observation process, or the imperfect detectability of species, from the ecological processes of interest governing species distributions. Occupancy studies come at a cost, however: the collection of additional data to account for nondetections at sites where the species is present. The most common occupancy designs (repeated‐measures designs) require repeat visits to sites or the use of multiple observers or detection methods. Time‐to‐detection methods have been identified as a potentially efficient alternative, requiring only one visit to each site by a single observer. A comparison of time‐to‐detection methods to repeated‐measures designs for visual encounter surveys would allow researchers to evaluate whether time‐to‐detection methods might be appropriate for their study system and can inform optimal survey design. We collected time‐to‐detection data during two different repeated‐measures design occupancy surveys for four amphibians and compared the performance of time‐to‐detection methods to the other designs using the location (potential bias) and precision of posterior distributions for occurrence parameters. We further used results of time‐to‐detection surveys to optimize survey design. Time‐to‐detection methods performed best for species that are widespread and have high detection probabilities and rates, but performed less well for cryptic species with lower probability of occurrence or whose detection was strongly affected by survey conditions. In all cases, single surveys were most efficient in terms of person‐hours expended, but under some conditions the survey duration required to achieve high detection probabilities would be prohibitively long for a single survey. Regardless of occupancy survey design, time‐to‐detection methods provide important information that can be used to optimize surveys, allowing researchers and resource managers to efficiently achieve monitoring and conservation goals. Collecting time‐to‐detection data while conducting repeated‐measures occupancy surveys requires only small modifications to field methods but could have large benefits in terms of time spent surveying in the long term.
Extracorporeal life support as bridge to recovery in yew poisoning: case reports and literature review
Authors: Hermes‐Laufer Julia , Meyer Martin , Rudiger Alain , Henze Julian , Enselmann Kai , Kupferschmidt Hugo , Müller Daniel , Herzog Aline , Bettex Dominique , Keller Dagmar I. , Krüger Bernard , Engeler Judith
Published: November 2020

Aims

This short communication aims to review the treatment of cardiogenic shock in patients with yew poisoning based on two case reports from our institution, focusing on the use of extracorporeal life support (ECLS).

Methods and results

We report two cases of Taxus baccata poisoning treated with ECLS at our institution and review the literature based on a search in PubMed and Google Scholar on the topic of yew poisoning and ECLS. All cases were combined for analysis of demographics, ECLS therapy, and outcome. Case 1: A 35‐year‐old woman developed polymorphic ventricular tachycardia followed by cardiovascular arrest 5 h after orally ingesting a handful of yew needles. Successful resuscitation required ECLS for 72 h due to ongoing cardiac arrhythmias and cardiogenic shock. The patient left the hospital without neurological sequelae after 10 days. Case 2: A 30‐year‐old woman developed refractory cardiac arrhythmias and circulatory arrest. Resuscitation included ECLS for 71 h. T. baccata needles found by gastroscopy confirmed the diagnosis. The patient had no neurologic deficits and was transferred to psychiatry after 11 days. Review of the literature: Nine case reports were found and analysed along with our two cases. Five out of the 11 (45%) patients were female. Median (range) age was 28 (19–46) years. T. baccata needles were ingested with a suicidal intention in all patients. Median (range) duration of ECLS was 70 h (24–120 h). Eight (73%) patients had full neurological recovery.

Conclusions

Yew poisoning is a differential diagnosis in young psychiatric patients presenting with polymorphic ventricular tachycardia and cardiogenic shock. A characteristic cardiac contraction pattern in echocardiography may present a diagnostic clue. The early use of ECLS is a valuable bridge to recovery in most of these patients.
Insights into heart failure hospitalizations, management, and services during and beyond COVID‐19
Authors: Charman Sarah J. , Velicki Lazar , Okwose Nduka C. , Harwood Amy , McGregor Gordon , Ristic Arsen , Banerjee Prithwish , Seferovic Petar M. , MacGowan Guy A. , Jakovljevic Djordje G.
Published: November 2020

Coronavirus disease 2019 (COVID‐19) is caused by severe acute respiratory syndrome coronavirus‐2. The clinical presentation of this virus mainly manifests in the respiratory system but may also lead to severe complications in the cardiovascular system. The global burden of COVID‐19 has led to an unprecedented need to gain further insight into patient outcomes, management, and clinical practice. This review aims to provide an overview of the current literature on heart failure (HF) hospitalizations, management, and care pathways for supporting patients during and beyond this pandemic. A literature review of five areas of interest was conducted and included: (i) HF hospitalization; (ii) recognizing the needs and supporting HF patients during COVID‐19; (iii) supporting rehabilitation services; (iv) transitioning to a telehealth framework; and (v) the need for evidence. Patients with new‐onset or existing HF are particularly vulnerable, but a significant reduction in HF hospital admissions has been reported. During these periods of uncertainty, the current care pathways for acute and elective cardiac patients have had to change with the relocation of HF services to protect the vulnerable and reduce transmission of COVID‐19. Optimizing community HF services has the potential to reduce the pressures on secondary care during the recovery from this pandemic. Telemedicine and virtual health care are emerging technologies and overcome the risk of in‐person exposure. Successful remote delivery of cardiac rehabilitation services has been reported during the pandemic. Delivery of a robust telehealth framework for HF patients will improve communication between clinician and patient. The reduction in HF admissions is a concern for the future and may result in unintended mortality. New‐onset and current HF patients must understand their diagnosis and future prognosis and seek help and support using the appropriate platform when needed. Realigning HF services and the use of telemedicine and virtual health care has great potential but needs to be carefully understood to ensure engagement and approval in this population to overcome barriers and challenges.
Heart failure development in obesity: underlying risk factors and mechanistic pathways
Authors: Jamaly Shabbar , Carlsson Lena , Peltonen Markku , Andersson‐Assarsson Johanna C. , Karason Kristjan
Published: November 2020

Aims

People with obesity are at risk for developing heart failure (HF), but little is known about the mechanistic pathways that link obesity with cardiac dysfunction.

Methods and results

We included 2030 participants from the Swedish Obese Subjects study who received conventional obesity treatment. First‐time detection of HF was obtained by cross‐checking the study population with the Swedish National Patient Register and the Swedish Cause of Death Register. We also examined if atrial fibrillation and myocardial infarction as time‐dependent variables could predict incident HF

The mean age of the study cohort was 48.7 years, and 28% were men. The mean body mass index at baseline was 40.1 kg/m2 and remained stable during a median follow‐up of 20.1 years. First‐time diagnosis of HF occurred in 266 of patients and was related to male sex, increasing age, greater waist–hip ratio, hypertension, higher cholesterol, diabetes mellitus, and elevated free thyroxine in univariable analysis. Estimated glomerular filtration rate was negatively related to HF risk. In multivariable analysis, atrial fibrillation, which is related to HF with preserved ejection fraction (HFpEF), and myocardial infarction, which is linked to HF with reduced ejection fraction (HFrEF), were strongly associated with incident HF with sub‐hazard ratios 3.75 (95% confidence interval: 2.72–5.18, P < 0.001) and 3.68 (95% confidence interval: 2.55–5.30, P < 0.001), respectively.

Conclusions

Both atrial fibrillation and myocardial infarction as time‐dependent variables were independently and strongly related to incident HF in people with excess body fat, suggesting two main obesity‐related mechanistic pathways leading to either HFpEF or HFrEF.
Crosstalk between the activated Slit2–Robo1 pathway and TGF‐β1 signalling promotes cardiac fibrosis
Authors: Liu Yunqi , Yin Ziwei , Xu Xueqin , Liu Chen , Duan Xiaoying , Song Qinlan , Tuo Ying , Wang Cuiping , Yang Jing , Yin Shengli
Published: November 2020

Aims

Previous reports indicated that the Slit2–Robo signalling pathway is involved in embryonic heart development and fibrosis in other solid organs, but its function in adult cardiac fibrosis has not been investigated. Here, we investigate the role of the Slit2–Robo1 signalling pathway in cardiac fibrosis.

Methods and results

The right atrial tissue samples were obtained from patients with valvular heart disease complicated by atrial fibrillation during heart valve surgery and from healthy heart donors. The fibrotic animal model is created by performing transverse aortic constriction (TAC) surgery. The Robo1, Slit2, TGF‐β1, and collagen I expression levels in human and animal samples were evaluated by immunohistochemistry and western blot analysis. Echocardiography measured the changes in heart size and cardiac functions of animals. Angiotensin II (Ang II), Slit2‐siRNA, TGF‐β1‐siRNA, recombinant Slit2, and recombinant TGF‐β1 were transfected to cardiac fibroblasts (CFs) respectively to observe their effects on collagen I expression level. The right atrial appendage of patients with valvular heart disease complicated by atrial fibrillation found significantly up‐regulated Slit2, Robo1, TGF‐β1, and collagen I expression levels. TAC surgery leads to heart enlargement, cardiac fibrosis, and up‐regulation of Slit2, Robo1, TGF‐β1, and collagen I expression levels in animal model. Robo1 antagonist R5 and TGF‐β1 antagonist SB431542 suppressed cardiac fibrosis in TAC mice. Treatment with 100 nM Ang II in CFs caused significantly increased Slit2, Robo1, Smad2/3, TGF‐β1, collagen I, PI3K, and Akt expression levels. Transfecting Slit2‐siRNA and TGF‐β1‐siRNA, respectively, into rat CFs significantly down‐regulated Smad2/3 and collagen I expression, inhibiting the effects of Ang II. Recombinant Slit2 activated the TGF‐β1/Smad signalling pathway in CFs and up‐regulated Periostin, Robo1, and collagen I expression.

Conclusions

The Slit2–Robo1 signalling pathway interfered with the TGF‐β1/Smad pathway and promoted cardiac fibrosis. Blockade of Slit2–Robo1 might be a new treatment for cardiac fibrosis.
Different Ratios of Corn and Coconut Oil Blends in High‐Fat Diets Influence Fat Deposition without Altering Metabolic Biomarkers in Male Rats
Authors: Voon Phooi Tee , Yong Xiou Shuang , Phang Lai Yee , Ng Tong Kok Wai , Lee Verna Kar Mun
Published: November 2020

The effects of high‐fat diets with the recommended dietary linoleic acid (LA) intake levels on health outcomes have not been studied extensively. This study investigated the effects of high‐fat diets containing different weight ratios of coconut and corn oil with LA levels of <1.00% of energy (very low LA), 2.80% of energy (low LA), 5.80% of energy (moderate LA), and 9.70% of energy (high LA) on fat deposition and selected metabolic biomarkers of male Sprague‐Dawley rats. Their initial and terminal body weights are recorded. Blood, adipose tissue, and liver samples are obtained for analysis after an 8‐week feeding intervention. Compared with the very low‐LA diet, the high‐LA diet resulted in higher body weight gain and epididymal fat deposition. No significant differences are observed in liver‐to‐body weight ratio, blood glucose, visfatin, and leptin levels between the test diets. Serum tumor necrosis factor‐alpha (TNF‐α), insulin, and C‐peptide levels do not significantly increase with the increase in dietary LA levels. High‐LA diet results in higher LA levels in the liver and adipose tissue. It is concluded that a high‐fat diet containing high LA levels induced body weight gain and epididymal fat deposition in rats but has no effect on selected metabolic biomarkers.

Practical applications: Linoleic acid (LA) (C18:2) plays an important role as one of the nutritional elements to meet the daily essential fatty acid requirements. However, a full understanding is perplexed by the various ways that LA can be included in the diet when there is a recommendation to substitute saturated fatty acid (SFA), trans‐ or n‐3 fatty acids intake. The data provide additional findings on the effects of excessive dietary intake of LA (C18:2) on fat deposition when different levels of SFAs are replaced.
Graphene for hydrogen energy storage ‐ A comparative study on GO and rGO employed in a modified reversible PEM fuel cell
Authors: Jindal Himanshu , Oberoi Amandeep Singh , Sandhu Inderjeet Singh , Chitkara Mansi , Singh Baljit
Published: November 2020

We present an experimental investigation on graphene for electrochemical hydrogen storage when employed in a modified reversible polymer electrolyte membrane (MRPEM) fuel cell. Synthesis of graphene nanomaterial is performed to obtain graphene oxide (GO) using the modified Hummers method. Oxides in GO are reduced to get reduced graphene oxide (rGO) using Cedrus deodara (CD) tree's leaf extract. Physical characterisation of the prepared GO and CD‐rGO is done to ascertain their properties, viz, internal pore surface area, average pore diameter, etc. Solid electrodes are fabricated from the prepared powdered samples of GO and CD‐rGO, and later tested in an MRPEM fuel cell. Electrochemical hydrogen storage capacity of GO and CD‐rGO is found to be 1.21 and 2.7 wt%, respectively. It is successfully demonstrated that hydrogen ions could be stored in a porous graphene electrode and recovered back. The obtained results are analysed to draw a relation between physical characteristics of graphene and electrochemical hydrogen adsorption. It is found that higher internal pore surface area attracts more hydrogen storage in ionic form. This research work is a maiden attempt to show, experimentally, the physical/chemical adsorption of hydrogen in graphene when employed in a reversible PEM fuel cell. This surely could contribute towards the development of a safe and efficient alternate powering source with many potential applications.
Nonvolatile taste compounds of Shanghai smoked fish: A novel three stages control techniques
Authors: Zhou Yu , Chen Shunsheng , Wang Xichang , Zhang Hongcai
Published: November 2020

In this work, the effect of processing stages including first soaking (FS), frying after first soaking (FFS), and second soaking (SS) on nonvolatile taste compounds of Shanghai smoked fish was investigated using high‐performance liquid chromatography (HPLC) and automatic amino acid analyzer. Results showed that the contents of free amino acids (FAAs) ranged from 396.94 to 585.79 mg/100 g and 5′‐inosine monophosphate (IMP, as main umami nucleotide) from 215.91 to 284.56 mg/100 g in Shanghai smoked fish, respectively. Moreover, the contents of Glu and Gly as main umami amino acids ranged from 1.64 to 107.32 mg/100 g and 61.61 to 108.88 mg/100 g, respectively. TAV values of IMP, Asp, and Glu in Shanghai smoked fish reached 11.38, 2.73, and 21.46, respectively. The obvious difference could be observed using principal component analysis (PCA) in three processing stages of Shanghai smoked fish. Therefore, probing into the nonvolatile flavor of Shanghai smoked fish could not only enrich the theoretical basis of flavor chemistry in freshwater fish fields, but probe into the formation mechanisms of taste compounds in further study.
Brain functional connectivity dynamics at rest in the aftermath of affective and cognitive challenges
Authors: Gaviria Julian , Rey Gwladys , Bolton Thomas , Delgado Jaime , Van De Ville Dimitri , Vuilleumier Patrik
Published: November 2020

Carry‐over effects on brain states have been reported following emotional and cognitive events, persisting even during subsequent rest. Here, we investigated such effects by identifying recurring co‐activation patterns (CAPs) in neural networks at rest with functional magnetic resonance imaging (fMRI). We compared carry‐over effects on brain‐wide CAPs at rest and their modulation after both affective and cognitive challenges. Healthy participants underwent fMRI scanning during emotional induction with negative valence and performed cognitive control tasks, each followed by resting periods. Several CAPs, overlapping with the default‐mode (DMN), salience, dorsal attention, and social cognition networks were impacted by both the preceding events (movie or task) and the emotional valence of the experimental contexts (neutral or negative), with differential dynamic fluctuations over time. Temporal metrics of DMN‐related CAPs were altered after exposure to negative emotional content (compared to neutral) and predicted changes in subjective affect on self‐reported scores. In parallel, duration rates of another attention‐related CAP increased with greater task difficulty during the preceding cognitive control condition, specifically in the negative context. These findings provide new insights on the anatomical organization and temporal inertia of functional brain networks, whose expression is differentially shaped by emotional states, presumably mediating adaptive homeostatic processes subsequent to behaviorally challenging events.
Inhibition of Long Noncoding RNA Linc‐Pint by Hepatitis C Virus in Infected Hepatocytes Enhances Lipogenesis
Authors: Khatun Mousumi , Sur Subhayan , Steele Robert , Ray Ranjit , Ray Ratna B.
Published: November 2020

Background and Aims

HCV often causes chronic infection in liver, cirrhosis, and, in some instances, HCC. HCV encodes several factors' those impair host genes for establishment of chronic infection. The long noncoding RNAs (lncRNAs) display diverse effects on biological regulations. However, their role in virus replication and underlying diseases is poorly understood. In this study, we have shown that HCV exploits lncRNA long intergenic nonprotein‐coding RNA, p53 induced transcript (Linc‐Pint) in hepatocytes for enhancement of lipogenesis.

Approach and Results

We identified a lncRNA, Linc‐Pint, which is significantly down‐regulated in HCV‐replicating hepatocytes and liver specimens from HCV infected patients. Using RNA pull‐down proteomics, we identified serine/arginine protein specific kinase 2 (SRPK2) as an interacting partner of Linc‐Pint. A subsequent study demonstrated that overexpression of Linc‐Pint inhibits the expression of lipogenesis‐related genes, such as fatty acid synthase and ATP‐citrate lyase. We also observed that Linc‐Pint significantly inhibits HCV replication. Furthermore, HCV‐mediated enhanced lipogenesis can be controlled by exogenous Linc‐Pint expression. Together, our results suggested that HCV‐mediated down‐regulation of Linc‐Pint enhances lipogenesis favoring virus replication and liver disease progression.

Conclusions

We have shown that SRPK2 is a direct target of Linc‐Pint and that depletion of SRPK2 inhibits lipogenesis. Our study contributes to the mechanistic understanding of the role of Linc‐Pint in HCV‐associated liver pathogenesis.
The role of landscape morphology on soil moisture variability in semi‐arid ecosystems
Authors: Srivastava Ankur , Saco Patricia M. , Rodriguez Jose F. , Kumari Nikul , Chun Kwok Pan , Yetemen Omer
Published: November 2020

Previous studies on semi‐arid ecosystems have shown high values of soil moisture variability (SMV) primarily induced by the combined effects of non‐uniform precipitation, incoming solar radiation, and soil and vegetation properties. However, the relative impact of these various factors on SMV has been difficult to evaluate due to limited availability of field data. In addition, only a limited number of studies have analysed the role of landscape morphology on SMV. Here we use numerical simulations of a simple hydrological model, the Bucket Grassland Model, to systematically analyse the effect of each contributing factor on SMV on two different landscape morphologies. The two different landform morphologies represent landscapes dominated respectively by either diffusive erosion or fluvial erosion processes. We conducted various simulations driven by a stochastically generated 100‐year climate time series, which is long enough to capture climatic fluctuations, in order to understand the effect of various soil moisture controlling factors on the spatiotemporal SMV. Our modelling results show that the fluvial dominated landscapes promote higher spatial SMV than the diffusive dominated ones. Further, the role of landform morphology on SMV is more pronounced in regions where the spatial variability of incoming solar radiation and precipitation is high.
Impaired interferon‐α expression in plasmacytoid dendritic cells in asthma
Authors: Lin Ting‐Yu , Lo Chun‐Yu , Tsao Kuo‐Chien , Chang Po‐Jui , Kuo Chih‐His Scott , Lo Yu‐Lun , Lin Shu‐Min , Hsieh Meng‐Heng , Wang Tsai‐Yu , Hsu Ping‐Chih , Lin Horng‐Chyuan
Published: November 2020

Background

Toll‐like receptor (TLR)‐7‐associated rhinovirus (RV) activation is involved in the pathogenesis of asthma. Plasmacytoid dendritic cells (pDCs) are the main interferon‐α‐producing cells against viruses.

Objective

To determine whether asthmatic patients and control subjects differ in terms of interferon‐α expression in pDCs under TLR‐7 or RV stimulation.

Methods

pDCs were identified in BDCA‐2+ and HLA‐DR+ peripheral blood mononuclear cells. Interferon‐α expression of pDCs was analyzed after TLR‐7 stimulation with or without interleukin 4 (IL‐4)/IL‐13 pretreatment. Interferon‐α expression was also analyzed after RV stimulation over periods of 24, 48, or 96 h with or without IL‐4 pretreatment. RV detection and molecular typing were assayed from throat swabs.

Results

Following TLR‐7 stimulation, the expression of intracellular interferon‐α was higher in the pDCs of normal subjects than those of asthmatic patients; however, pretreatment with IL‐4 was shown to reduce this effect. After 48‐ and 96‐h RV stimulation, we observed a notable increase in the production of interferon‐α of pDCs in normal subjects but not in asthmatic patients. Baseline interferon‐α expression in pDCs and the incidence of asthma exacerbation to emergency was higher among the 13% of patients identified as rhinovirus+ than among their RV counterparts.

Conclusion

Our study discovered the response to TLR‐7 stimulation in pDCs was compromised and the sustainability of interferon‐α expression to RV stimulation was reduced in pDCs of asthmatic patients, which provide further evidence of defective innate response and subspeciality to RV infection in asthma. The high exacerbation history founded in RV+ patients agrees with these findings. Further research is required for the modulatory effect of IL‐4 on TLR‐7 stimulated pDCs.
Progress, challenges and ways forward supporting cancer surveillance in Latin America
Authors: Piñeros Marion , Abriata María Graciela , de Vries Esther , Barrios Enrique , Bravo Luis Eduardo , Cueva Patricia , de Camargo Cancela Marianna , Fernández Leticia , Gil Enrique , Luciani Silvana , Pardo Constanza , Zoss Walter , Bray Freddie , Mery Les
Published: November 2020

Population‐based cancer registries (PBCRs) are the only means to provide reliable incidence and survival data as a basis for policy‐making and resource allocations within cancer care. Yet, less than 3% and 10% of the respective populations of Central America and South America are covered by high‐quality cancer registries. The Global Initiative for Cancer Registry Development provides support to improve this situation via the International Agency for Research on Cancer Regional Hub for Latin America. In this paper, we summarize activities (advocacy, technical assistance, training and research) over the last 5 years, their impact and current challenges, including the implementation of new PBCR in four countries in the region. Despite the favorable political support to cancer registration in many countries, the sustainability of cancer registration remains vulnerable. Renewed efforts are needed to improve data quality in Latin America while ensuring maximum visibility of the data collected by disseminating and promoting their use in cancer control.
Human splenic TER cells: A relevant prognostic factor acting via the artemin‐GFRα3‐ERK pathway in pancreatic ductal adenocarcinoma
Authors: Li Tian‐Jiao , Li Hao , Zhang Wu‐Hu , Xu Shuai‐Shuai , Jiang Wang , Li Shuo , Gao He‐Li , Han Xuan , Xu Hua‐Xiang , Wu Chun‐Tao , Wang Wen‐Quan , Yu Xian‐Jun , Liu Liang
Published: November 2020

Splenectomy is routinely performed during distal or total pancreatectomy (DP or TP) for pancreatic ductal adenocarcinoma (PDAC), but information about its oncological value is limited. TER cells, nonimmune cells discovered in the spleens of tumour‐bearing mice, are elicited by tumours and promote tumour progression, while their role in the clinical outcomes of patients with PDAC remains unclear. In our study, postoperative specimens from 622 patients who underwent DP or TP with splenectomy were analysed by flow cytometry or immunofluorescence, and the relationship between splenic TER cell count and clinical parameters was calculated. We also purified human TER cells for functional experiments and mechanistic studies. We found that TER cell numbers were increased only in the spleens of patients with PDAC but not in PDAC tissue and adjacent pancreatic tissue. High splenic TER cell counts independently predicted poor prognosis (P < .001) and indicated large tumour size, lymph node metastasis, advanced 8th AJCC/mAJCC stage and high CA19‐9 classification (all P < .050) in patients with PDAC. Mechanistic analysis showed that TER cells express artemin, which facilitates the proliferation and invasion of PDAC cells by activating GFRα3‐ERK signalling. Our study reveals that TER cell count is an indicator of poor prognosis of PDAC, while splenectomy during pancreatic surgery might provide oncological benefits in addition to ensuring the radical resection of PDAC.