bluuebunny/crossref_metadata_2025 huggingface dataset:
Recommendations for cellular and molecular pathology input into clinical trials: a systematic review and meta‐aggregation
Authors: Lim Shujing Jane , Gurusamy Kurinchi , O'Connor Daniel , Shaaban Abeer M , Brierley Daniel , Lewis Ian , Harrison David , Kendall Timothy James , Robinson Max
Published: February 2021

The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement was developed to provide guidance for inclusion of key methodological components in clinical trial protocols. However, these standards do not include guidance specific to pathology input in clinical trials. This systematic review aims to synthesise existing recommendations specific to pathology practice in clinical trials for implementation in trial protocol design. Articles were identified from database searches and deemed eligible for inclusion if they contained: (1) guidance and/or a checklist, which was (2) pathology‐related, with (3) content relevant to clinical trial protocols or could influence a clinical trial protocol design from a pathology perspective and (4) were published in 1996 or later. The quality of individual papers was assessed using the AGREE‐GRS (Appraisal of Guidelines for REsearch & Evaluation – Global Rating Scale) tool, and the confidence in cumulative evidence was evaluated using the GRADE‐CERQual (Grading of Recommendations Assessment, Development and Evaluation–Confidence in Evidence from Reviews of Qualitative research) approach. Extracted recommendations were synthesised using the best fit framework method, which includes thematic analysis followed by a meta‐aggregative approach to synthesis within the framework. Of the 10 184 records screened and 199 full‐text articles reviewed, only 40 guidance resources met the eligibility criteria for inclusion. Recommendations extracted from 22 guidance documents were generalisable enough for data synthesis. Seven recommendation statements were synthesised as follows: (1) multidisciplinary collaboration in trial design with early involvement of pathologists, particularly with respect to the use of biospecimens and associated biomarker/analytical assays and in the evaluation of pathology‐related parameters; (2) funding and training for personnel undertaking trial work; (3) selection of an accredited laboratory with suitable facilities to undertake scheduled work; (4) quality assurance of pathology‐related parameters; (5) transparent reporting of pathology‐related parameters; (6) policies regarding informatics and tracking biospecimens across trial sites; and (7) informed consent for specimen collection and retention for future research.
Elective neck dissection versus positron emission tomography–computed tomography–guided management of the neck in clinically node‐negative early oral cavity cancer: A cost–utility analysis
Authors: Noel Christopher W. , Forner David , Goldstein David P. , Metser Ur , Ferris Robert L. , Waldron John , de Almeida John R.
Published: February 2021

Background

In early oral cavity cancer, elective neck dissection (END) for the clinically node‐negative (cN0) neck improves survival compared with observation. This paradigm has been challenged recently by the use of positron emission tomography–computed tomography (PET‐CT) imaging in the cN0 neck. To inform this debate, we performed an economic evaluation comparing PET‐CT–guided therapy with routine END in the cN0 neck.

Methods

Patients with T1‐2N0 lateralized oral tongue cancer were analyzed. A Markov model over a 40‐year time horizon simulated treatment, disease recurrence, and survival from a US health care payer perspective. Model parameters were derived from a review of the literature.

Results

The END strategy was dominant, with a cost savings of $1576.30 USD, an increase of 0.055 quality‐adjusted life years (QALYs), a net monetary benefit of $4303 USD, and a 0.22 life‐year advantage. END was sensitive to variation in cost and utilities in deterministic and probabilistic sensitivity analyses. PET‐CT became the preferred strategy when decreasing occult nodal disease to 18% and increasing the negative predictive value (NPV) of PET‐CT to 89% in 1‐way sensitivity analyses. In probabilistic sensitivity analysis, assuming a cost effectiveness threshold of $50,000 USD/QALY, END was dominant in 64% of simulations and cost effective in 69.8%.

Conclusion

END is a cost‐effective strategy compared with PET‐CT in patients who have node‐negative oral cancer. Although lower PET standardized uptake value thresholds would result in fewer false negatives and improved NPV, it is still uncertain that PET‐CT would be cost effective, as this would likely result in more false positive tests.
Insulating Composites Made from Sulfur, Canola Oil, and Wool**
Authors: Bu Najmah Israa , Lundquist Nicholas A. , Stanfield Melissa K. , Stojcevski Filip , Campbell Jonathan A. , Esdaile Louisa J. , Gibson Christopher T. , Lewis David A. , Henderson Luke C. , Hasell Tom , Chalker Justin M.
Published: February 2021

An insulating composite was made from the sustainable building blocks wool, sulfur, and canola oil. In the first stage of the synthesis, inverse vulcanization was used to make a polysulfide polymer from the canola oil triglyceride and sulfur. This polymerization benefits from complete atom economy. In the second stage, the powdered polymer was mixed with wool, coating the fibers through electrostatic attraction. The polymer and wool mixture were then compressed with mild heating to provoke S−S metathesis in the polymer, which locks the wool in the polymer matrix. The wool fibers imparted tensile strength, insulating properties, and reduced the flammability of the composite. All building blocks are sustainable or derived from waste and the composite is a promising lead on next‐generation insulation for energy conservation.
Irigenin alleviates angiotensin II‐induced oxidative stress and apoptosis in HUVEC cells by activating Nrf2 pathway
Authors: Zhang Qi , Xue Tao , Guan Jianming , Wang Wei , Shi Ji , Lu Jianzhong , Jiang Xiping
Published: February 2021

Endothelial dysfunction is closely related to various cardiovascular diseases. Oxidative stress and apoptosis are involved in the progress of endothelial dysfunction. Irigenin (IR) has antioxidative properties. We investigated IR as a novel therapy for angiotensin II (Ang II)‐induced endothelial dysfunction and explored the potential mechanisms of IR. After human umbilical vein endothelial cell lines (HUVECs) were treated with Ang II (100, 200, 300 and 400 nmol/L) alone, IR (2.5, 5, 10, 20 and 40 μmol/L) alone or Ang II plus IR for 24 h, HUVECs viability, lactate dehydrogenase (LDH), apoptosis, oxidative stress, apoptosis‐related protein and nuclear factor E2‐related factor 2 (Nrf2) levels were detected by Cell Counting Kit (CCK)‐8 assay, enzyme‐linked immunosorbent assay, flow cytometry and western blot. Transfection rate of Nrf2 was detected by western blot. In the next rescue experiment, we used silent Nrf2 (siNrf2) to verify the previous experimental results. Different concentrations' Ang II repressed HUVECs viability and increased LDH release, and different concentrations' IR did not affect HUVECs viability or LDH release. Furthermore, IR elevated cell viability and Nrf2 level, inhibited LDH release, apoptosis, oxidative stress and apoptosis‐related protein levels in Ang II‐induced HUVECs. More important, siNrf2 suppressed the expression of Nrf2, and siNrf2 abrogated the protective effect of IR on Ang II‐induced Nrf2 expression, cell viability, LDH activity, oxidative stress generation and apoptosis‐related protein in HUVECs. IR protected HUVECs from Ang II‐induced oxidative stress and apoptosis injury by activating Nrf2 pathway.
Prediction of regional wildfire activity in the probabilistic Bayesian framework of Firelihood
Authors: Pimont François , Fargeon Héléne , Opitz Thomas , Ruffault Julien , Barbero Renaud , Martin‐StPaul Nicolas , Rigolot Eric , RiviÉre Miguel , Dupuy Jean‐Luc
Published: February 2021

Modeling wildfire activity is crucial for informing science‐based risk management and understanding the spatiotemporal dynamics of fire‐prone ecosystems worldwide. Models help disentangle the relative influences of different factors, understand wildfire predictability, and provide insights into specific events. Here, we develop Firelihood, a two‐component, Bayesian, hierarchically structured, probabilistic model of daily fire activity, which is modeled as the outcome of a marked point process: individual fires are the points (occurrence component), and fire sizes are the marks (size component). The space‐time Poisson model for occurrence is adjusted to gridded fire counts using the integrated nested Laplace approximation (INLA) combined with the stochastic partial differential equation (SPDE) approach. The size model is based on piecewise‐estimated Pareto and generalized Pareto distributions, adjusted with INLA. The Fire Weather Index (FWI) and forest area are the main explanatory variables. Temporal and spatial residuals are included to improve the consistency of the relationship between weather and fire occurrence. The posterior distribution of the Bayesian model provided 1,000 replications of fire activity that were compared with observations at various temporal and spatial scales in Mediterranean France. The number of fires larger than 1 ha across the region was coarsely reproduced at the daily scale, and was more accurately predicted on a weekly basis or longer. The regional weekly total number of larger fires (10–100 ha) was predicted as well, but the accuracy degraded with size, as the model uncertainty increased with event rareness. Local predictions of fire numbers or burned areas also required a longer aggregation period to maintain model accuracy. The estimation of fires larger than 1 ha was also consistent with observations during the extreme fire season of the 2003 unprecedented heat wave, but the model systematically underrepresented large fires and burned areas, which suggests that the FWI does not consistently rate the actual danger of large fire occurrence during heat waves. Firelihood enabled a novel analysis of the stochasticity underlying fire hazard, and offers a variety of applications, including fire hazard predictions for management and projections in the context of climate change.
Recent Advances in Retained and Dehydrogenative Dual Functionalization Chemistry
Authors: Moriyama Katsuhiko
Published: February 2021

Dual functionalization in organic synthesis is an elegant and powerful method for simultaneously introducing two different functional groups regio‐selectively into a target molecule. In this review, the author describes recent advances in dual functionalization chemistry, focusing on retained dual functionalization and dehydrogenative dual functionalization.
Butterfly Mesogens Based on Carbazole, Fluorene or Fluorenone: Mesomorphous, Gelling, Photophysical, and Photoconductive Properties
Authors: Hang Jun‐Fang , Lin Hang , Zhao Ke‐Qing , Hu Ping , Wang Bi‐Qin , Monobe Hirosato , Zhu Chenhui , Donnio Bertrand
Published: February 2021

We report a straightforward and generic synthesis of several new series of annulated π‐extended poly‐(hetero)aromatic hydrocarbons (PAH), with carbazole, fluorene and fluorenone central building blocks by the Suzuki‐Miyaura/Scholl tandem reactions. The corresponding series of ditriphenylene discogens with a carbazole or a fluorenone central core, respectively, possess hexagonal columnar mesophases with broad mesophase ranges and high clearing points, as well as demonstrate a strong aggregation tendency in organic solvents as supergelators. The laterally‐substituted ditriphenylene mesogens based on dimethyl‐fluorene core exhibit a rich polymorphism with rectangular and hexagonal columnar mesophases from low temperatures onward, whereas their dioctyl‐fluorene homologues melt directly into the isotropic liquid without showing mesophases. These latter family of compounds are luminescent with very high fluorescent quantum yields, of around 70 % in solution, and show outstanding photocurrent behavior with charge carrier mobility in the 10−2 cm2 V−1 s−1 range, as measured by photocurrent transient time‐of‐flight (TOF) technique. This straightforward molecular design and simple synthetic strategy proved to be both potent and resilient, and could be generally applied to the fabrication of a great variety of other heteroarene molecular systems as organic semiconductors and electroluminescent materials for potentially low‐cost applications.
Copper(II)‐Catalyzed Aminohalogenation of Alkynyl Carbamates
Authors: Giofrè Sabrina , Loro Camilla , Molteni Letizia , Castellano Carlo , Contini Alessandro , Nava Donatella , Broggini Gianluigi , Beccalli Egle M.
Published: February 2021

A useful aminohalogenation reaction for the cyclization of O‐alkynyl carbamates under copper catalysis has been developed. N‐Halosuccinimides have been used as a halogen source. The intramolecular C−N bond formation occurs selectively affording haloalkylidene substituted heterocycles. Just in the case of α,α‐cyclohexyl‐substituted propargyl carbamate, the alkoxyhalogenation pathway was operative. The mechanism for the two alternative reaction pathways was investigated by modeling the corresponding transition states at the DFT level.
Computational analysis of a dual‐port semi‐circular patch antenna combined with Koch curve fractals for ultra‐wideband systems
Authors: Sohi Arashpreet K. , Kaur Amanpreet
Published: February 2021

This paper presents a two‐port microstrip‐fed semi‐circular patch antenna integrated with Koch curve fractals and common ground with defected ground structure for the effective implementation in handheld ultra‐wideband (UWB) systems. The proposed array is engraved on a 1.57 mm thick FR‐4 substrate with an overall array size of 30.5 × 47 × 1.64 mm3. The parametric analysis of the proposed array indicates that the two optimized Koch curve fractal (second iteration order) radiators (upper substrate layer) provides an optimum matching performance in a wide operational band (4.395–10.184 GHz, 79.4%) and minimizes the patch area by 41.2% as compared to the conventional circular patch. To realize good port‐to‐port isolation (S21/S12 ≤ −16.8 dB), the reduced ground is slotted and incorporated with a funnel‐shaped decoupling structure at the center. The prototype of the proposed array is fabricated and experimentally tested to justify the simulated S‐parameter results. All diversity metrics like envelope correlation coefficient, diversity gain (DG), mean effective gain, channel capacity loss, and total active reflection coefficient lie within their acceptable limits which affirm a high signal‐to‐noise ratio and the proficiency of the proposed array in the development of high data‐rate UWB communication devices.
Effect of nitriding pre‐treatment on the tribocorrosion behavior of physical vapor deposition‐coated tool steel
Authors: Kim Hyunsoo , Mandel Marcel , Dalke Anke , Biermann Horst , Krüger Lutz
Published: February 2021

Cr‐Al‐Ti‐B‐N hard coating is deposited onto the AISI D2 cold‐worked tool steel by means of a hybrid physical vapor deposition (PVD) technique. The effect of plasma nitriding pre‐treatment on the tribocorrosion behavior of the hard‐coated tool steel is investigated using a ball‐on‐disc sliding wear tribometer equipped with an electrochemical testing set up. Tribocorrosive characteristics are analyzed by optical and scanning electron microscopy, 3D surface profilometry, and open circuit potential (OCP) measurement. The coefficient of friction and OCP varies depending on the degree of damage to the hard coating, such that the point at which the substrate is first exposed can be identified by these measurements. The plasma nitriding pretreatment increases the surface hardness significantly and, therefore, the adhesion of the PVD hard coating to the substrate material. As a consequence, the material's wear resistance is enhanced and its durability against tribocorrosion is improved.
Medical and pharmacokinetic effects of nanopolyphenols: A systematic review of clinical trials
Authors: Rambaran Theresa F. , Nordström Anna
Published: February 2021

A significant percentage of the population has been turning to herbal remedies either as a sole treatment option or in combination with other drugs. Efforts to increase the production of therapeutic remedies from these scaffolds have therefore amplified. A fundamental aim when developing new drugs is to develop drugs that have virtually no or less adverse effects than those currently available while being efficacious. Several approaches have been undertaken to use nanotechnology to develop nanoencapsulated polyphenols for use in therapeutics in an attempt to improve their physicochemical properties, bioavailability, and efficacy. This review covers the types of nanopolyphenols that have been evaluated in clinical trials against various medical conditions and their outcomes. Medical conditions covered include cardiometabolic diseases, inflammatory diseases, and cancer and in almost all instances the nanoencapsulated polyphenol produced a positive outcome. Similar outcomes were also reported for pharmacokinetic analyses. The review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews as CRD42020172642.
Association of serum 25‐hydroxy vitamin D with obesity‐related indices in Chinese adults: A cross‐sectional study
Authors: Ren Zhongxia , Zhao Ai , Wang Yan , Meng Liping , Man‐Yau Szeto Ignatius , Yang Chenlu , Wang Meichen , Zhang Jian , Wu Wei , Wang Peiyu , Zhang Yumei
Published: February 2021

Obesity has been a well‐known risk factor of low‐level serum vitamin D. Compared with the traditional obesity‐related indicator (body mass index, BMI), associations for two novel anthropometric indices, a body shape index (ABSI) and body roundness index (BRI) with vitamin D deficiency or insufficiency, still remain unclear. This study aimed to assess the associations of serum 25‐hydroxy vitamin D (25(OH)D) status with these three obesity‐related indices among Chinese adults. A total of 1666 individuals were included. Anthropometric measurements were performed to calculate the indices, and fasting blood was collected to determine serum 25(OH)D deficiency (<12 ng/ml) and insufficiency (12–20 ng/ml). Deficiency or insufficiency of 25(OH)D was found in 37.5% and 43.1% of the participants, respectively. After adjustment for potential confounders, a significantly increased prevalence of 25(OH)D deficiency was observed for higher ABSI (OR Q4 vs Q1 2.334, 95% CI 1.458–3.734; p trend = 0.002) and BRI (OR Q4 vs Q1 2. 215, 95%CI 1.365–3.594; p trend = 0.010), and for higher BMI in men. Regarding 25(OH)D insufficiency, a significant association was also found for ABSI (OR Q4 vs Q1 2.372, 95%CI 1.558–3.612; p trend = 0.001). The area under the ROC of ABSI (0.731, 95%CI 0.687–0.774) for predicting a low level of 25(OH)D was significantly larger than that of BMI (0.695, 95%CI 0.649–0.741) in men, but not in women. A positive association between obesity and lower 25(OH)D serum concentration was found among Chinese adults. Besides BMI, novel obesity‐related indicator, ABSI and BRI were associated with lower serum 25(OH)D to some extent, and further studies are needed to clarify their potential to be used as screening tools in clinical practice.
Enhancing aircraft cabin comfort to compete with high‐speed trains: A survey in China
Authors: Wang Jin , Zhi Jin‐Yi , Xiang Ze‐Rui , Du Jun , Chen Jian‐Ping , He Si‐Jun , Du Yang
Published: February 2021

To improve the competitiveness of air transport, this study proposed a method for devising a differentiated comfort enhancement strategy and compared the comfort of aircraft and high‐speed trains (HST). Structural equation modeling (SEM) was used to analyze the similarities and differences in the factors influencing comfort in aircraft cabins and HST compartments. The results showed that comfort in wide‐body aircraft cabins was mainly influenced by “food & beverage” and “personal in‐flight entertainment” (personal IFE), whereas comfort in narrow‐body aircraft and HSTs was mainly influenced by the “passenger interface.” The results also showed no significant difference in the overall comfort evaluation of the passenger interface between narrow‐body aircraft and HSTs. Furthermore, aircraft passenger ratings were significantly lower than those of HST passengers with regard to “spaciousness,” “seat comfort,” and “seat and cabin and compartment aesthetics.” The study results suggest that given competition from HSTs, airlines should use different comfort enhancement strategies for wide‐body and narrow‐body aircraft cabins.
An empirical model for predicting the length of a capillary tube
Authors: Freegah Basim , Saleh Qasim , Theeb Maathe A.
Published: February 2021

Any refrigerant device consists of several parts, and one of the most significant parts is the expansion device. This expansion device can be classified into several types according to the size of the refrigeration system. The capillary tube is used usually with a small refrigerant system size to reduce the higher pressure in the condenser into the low pressure in the evaporator. In this study, the effect of the capillary tube's diameter and that of the temperature of the condenser and evaporator on the length of such a device has been theoretically studied. Furthermore, a validation between the theoretical analysis and experimental findings from the literature review has been carried out. To achieve the theoretical aspect, MATLAB code has been developed. The results showed that the maximum difference between the theoretical and experimental results regarding temperature and pressure refrigeration is around 5% and 3.4%, respectively. Also, the results depict that the inner diameter and the condenser temperature have an effect on the length of the capillary tube. However, the effect of the inner diameter is higher compared with the condenser temperature. In addition, an equation to predict the length of the capillary tube has been developed with an accuracy of 98%. This equation is created as a function of the capillary tube's diameter and the temperature of the condenser and the evaporator. Moreover, this equation can be used to predict the length of the capillary tube for small refrigeration devices, especially those operating under 10 KW. The findings of this study can help make a mathematical approach used for the design of the capillary tube simpler and easier to apply.
The unveiled reality of human papillomavirus as risk factor for oral cavity squamous cell carcinoma
Authors: Nauta Irene H. , Heideman Daniëlle A. M. , Brink Arjen , van der Steen Berdine , Bloemena Elisabeth , Koljenović Senada , Baatenburg de Jong Robert J. , Leemans C. René , Brakenhoff Ruud H.
Published: February 2021

The prognostic impact of human papillomavirus (HPV) in oropharyngeal cancer is generally acknowledged, and HPV‐status is assessed routinely in clinical practice. Paradoxically, while the oral cavity seems the predilection site for productive HPV‐infections, figures on HPV‐attribution in oral cavity squamous cell carcinoma (OCSCC) differ widely, and prognostic impact is uncertain. Major obstacles are the lack of reproducible assays to detect HPV in nonoropharyngeal cancers, the relatively small cohorts studied and consequently the shortfall of convincing data. In our study, we used a validated, nucleic acid‐based workflow to assess HPV‐prevalence in a consecutive cohort of 1016 OCSCCs, and investigated its prognostic impact. In parallel, we analyzed p16‐immunohistochemistry (p16‐IHC) as surrogate marker for transforming HPV‐infection and independent prognosticator. All OCSCC‐patients diagnosed between 2008 and 2014 at two Dutch university medical centers were included (N = 1069). Formalin‐fixed, paraffin‐embedded (FFPE)‐samples of 1016 OCSCCs could be retrieved. Punch biopsies were taken from the tumor area in the FFPE‐blocks and tested for HPV. P16‐IHC was performed on 580 OCSCCs, including all HPV‐positive tumors. From 940 samples (92.5%), nucleic acids were of sufficient quality for HPV‐testing. In total, 21 (2.2%) OCSCCs were HPV DNA‐positive. All HPV DNA‐positive tumors were E6 mRNA‐positive and considered as true HPV‐positive. There was no difference in survival between HPV‐positive and HPV‐negative OCSCCs. In total, 46 of 580 (7.9%) OCSCCs were p16‐immunopositive, including all HPV‐positive tumors. Survival was comparable in p16‐positive and p16‐negative OCSCCs. To conclude, HPV‐prevalence is very low in OCSCC and neither HPV‐status nor p16‐status affects outcome. Based on these data, determining HPV‐status in OCSCC seems irrelevant for clinical management.
Low positive predictive value of computed tomography screening for lung cancer irrespective of commonly employed definitions of target population
Authors: Krilaviciute Agne , Brenner Hermann
Published: February 2021

Screening for lung cancer (LC) by low‐dose computed tomography (LDCT) has been demonstrated to reduce LC mortality in randomized clinical trials (RCTs), and its implementation is in preparation in many countries. However, definition of the target population, which was based on various combinations of age ranges and definitions of heavy smoking in the RCTs, is subject to ongoing debate. Using epidemiological data from Germany, we aimed to estimate prevalence of preclinical LC and positive predictive value (PPV) of LDCT in potential target populations defined by age and smoking history. Populations aged 50 to 69, 55 to 69, 50 to 74 and 55 to 79 years were considered in this analysis. Sex‐specific prevalence of preclinical LC was estimated using LC incidence data within those age ranges and annual transition rates from preclinical to clinical LC obtained by meta‐analysis. Prevalence of preclinical LC among heavy smokers (defined by various pack‐year thresholds) within those age ranges was estimated by combining LC prevalence in the general population with proportions of heavy smokers and relative risks for LC among them derived from epidemiological studies. PPVs were calculated by combining these prevalences with sensitivity and specificity estimates of LDCT. Estimated prevalence of LC was 0.3% to 0.5% (men) and 0.2% to 0.3% (women) in the general population and 0.8% to 1.7% in target populations of heavy smokers. Estimates of PPV of LDCT were <20% for all definitions of target populations of heavy smokers. Refined preselection of target populations would be highly desirable to increase PPV and efficiency of LDCT screening and to reduce numbers of false‐positive LDCT findings.
Metabolic factors and the risk of small intestine cancers: Pooled study of 800 000 individuals in the metabolic syndrome and cancer project
Authors: Nagel Gabriele , Bjørge Tone , Jaensch Andrea , Peter Raphael S. , Häggström Christel , Lang Alois , Engeland Anders , Teleka Stanley , Jirström Karin , Lindquist David , Stattin Pär , Ulmer Hanno , Concin Hans , Stocks Tanja
Published: February 2021

To explore the largely unknown etiology of small intestine cancer, we examined metabolic factors and risk of small intestine cancer overall and by subtypes. Among 404 220 women and 403 265 men in six European cohorts, we applied Cox regression with adjustment for smoking and body mass index (BMI), to calculate sex‐specific hazard ratios (HRs) of small intestine cancer by levels of BMI, mean arterial pressure (MAP) and plasma total cholesterol, triglycerides and glucose. We also calculated HRs for these factors combined (metabolic score; MetS) and used Wald test statistics to investigate pairwise interactions between metabolic factors on risk. We also performed analyses separately per subtype (neuroendocrine tumors [NETs] and adenocarcinomas). During a median follow‐up of 16.9 years, 144 women and 195 men were diagnosed with small intestine cancer, including 184 NETs and 99 adenocarcinomas. Among men, no main associations or interactions between metabolic factors were observed in relation to the risk of small intestine cancer. Among women, triglycerides were positively and linearly associated with risk (HR per standard deviation [SD]: 1.23, 95% confidence interval [CI]: 1.04‐1.46), and a positive association was also observed for the MetS (HR per SD: 1.25, 95% CI: 1.02‐1.52). Positive interactions were observed among women between triglycerides and cholesterol (P = .0005), and between MAP and glucose (P = .009), on risk. Glucose was positively associated with adenocarcinomas among women. This large, prospective study suggests that elevated triglycerides, and metabolic factors in interaction, confer an increased risk of small intestine cancer among women, but not among men.
The impact of the COVID‐19 pandemic on the short‐term survival of patients with cancer in Northern Portugal
Authors: Morais Samantha , Antunes Luís , Rodrigues Jéssica , Fontes Filipa , Bento Maria José , Lunet Nuno
Published: February 2021

The COVID‐19 pandemic led to potential delays in diagnosis and treatment of cancer patients, which may negatively affect the prognosis of these patients. Our study aimed to quantify the impact of COVID‐19 on the short‐term survival of cancer patients by comparing a period of 4 months after the outbreak began (2 March 2020) with an equal period from 2019. All cancer cases of the esophagus, stomach, colon and rectum, pancreas, lung, skin‐melanoma, breast, cervix, and prostate, from the Portuguese Oncology Institute of Porto (IPO‐Porto) and diagnosed between 2 March and 1 July of 2019 (before COVID‐19) and 2020 (after COVID‐19) were identified. Information regarding sociodemographic, clinical and treatment characteristics were collected from the cancer registry database and clinical files. Vital status was assessed to 31 October of the respective years. Cox proportional hazards regression was used to estimate crude and propensity score‐adjusted hazards ratio (HR) and 95% confidence intervals (95% CIs) of death. During follow‐up to 31 October, there were 154 (11.8%) deaths observed before COVID‐19 and 131 (17.2%) after COVID‐19, corresponding to crude and adjusted HRs (95% CI) of 1.51 (1.20‐1.91) and 1.10 (0.86‐1.40), respectively. Significantly higher adjusted hazards of death were observed for patients with Stage III cancer (HR = 2.37; 95% CI: 1.14‐4.94) and those undergoing surgical treatment (HR = 3.97; 95% CI: 1.14‐13.77) or receiving radiotherapy (HR = 1.96; 95% CI: 1.96‐3.74), while patients who did not receive any treatment had a lower mortality hazards (HR = 0.62; 95% CI: 0.46‐0.83). The higher overall short‐term mortality observed during the COVID‐19 pandemic largely reflects the effects of the epidemic on the case‐mix of patients being diagnosed with cancer.
Antiepileptic drugs and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer
Authors: Salminen Jukka K. , Kuoppamäki Viivu , Talala Kirsi , Taari Kimmo , Mäkinen Jussi , Peltola Jukka , Tammela Teuvo L. J. , Auvinen Anssi , Murtola Teemu J.
Published: February 2021

Antiepileptic drugs (AEDs) with histone deacetylase (HDAC) inhibitor properties decrease prostate cancer (PCa) cell proliferation in vitro. A population‐based cohort of 78 615 men was used to evaluate the risk of PCa among users of AEDs. Study population was linked to the Finnish national prescription database to obtain information on individual medication reimbursements in 1996 to 2015. Cox regression with antiepileptic medication use as a time‐dependent variable was used to analyze PCa risk overall, and low, medium and high‐risk PCa separately. The analysis was adjusted for age, screening trial arm, and other drugs in use, including statins, antidiabetic drugs, antihypertensive drugs, aspirin, and nonsteroidal anti‐inflammatory drugs. Compared to the nonusers of AEDs, overall PCa risk was decreased among AED users (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.76‐0.96). A similar PCa risk decrease was observed among users of HDACi AEDs (HR = 0.87, 95% CI = 0.76‐1.01), but no risk difference was found when comparing HDACi AED users to users of other AEDs (HR = 0.98, 95% CI = 0.76‐1.27). Our study showed a decrease in overall PCa risk among men using AEDs compared to nonusers. The risk associations were similar for HDAC inhibitors as for AEDs in general.
Tissue‐engineered nerve graft using silk‐fibroin/polycaprolactone fibrous mats decorated with bioactive cerium oxide nanoparticles
Authors: Saremi Jamileh , Khanmohammadi Mehdi , Azami Mahmoud , Ai Jafar , Yousefi‐Ahmadipour Aliakbar , Ebrahimi‐Barough Somayeh
Published: February 2021

The main aim of this study was to evaluate the efficacy of cerium oxide nanoparticles (CNPs) encapsulated in fabricated hybrid silk‐fibroin (SF)/polycaprolactone (PCL) nanofibers as an artificial neural guidance conduit (NGC) applicable for peripheral nerve regeneration. The NGC was prepared by PCL and SF filled with CNPs. The mechanical properties, contact angle, and cell biocompatibility experiments showed that the optimized concentration of CNPs inside SF and SF/PCL wall of conduits was 1% (wt/wt). The SEM image analysis showed the nanoscale texture of the scaffold in different topologies depend on composition with fiber diameters at about 351 ± 54 nm and 420 ± 73 nm respectively for CNPs + SF and CNPs + SF/PCL fibrous mats. Furthermore, contact angle measurement confirmed the hydrophilic behavior of the membranes, ascribable to the SF content and surface modification through modified methanol treatment. The balance of morphological and biochemical properties of hybrid CNPs 1% (wt/wt) + SF/PCL construct improves cell adhesion and proliferation in comparison with lower concentrations of CNPs in nanofibrous scaffolds. The release of CNPs 1% (wt/wt) from both CNPs + SF and CNPs+ SF/PCL fibrous mats was highly controlled and very slow during the extended time of incubation until 60 days. Fabricated double‐layered NGC using CNPs + SF and CNPs + SF/PCL fibers was consistent for application in nervous tissue engineering and regenerative medicine from a structural and biocompatible perspective.
Más Fuertes Juntos: Attachment relationship quality, but not demographic risk, predicts psychopathology in Latinx mother‐youth dyads
Authors: Borelli Jessica L. , Russo Lyric N. , Arreola Jose , Cervantes Breana R. , Hecht Hannah K. , Leal Francisca , Montiel Gloria , Paredes Paulina , Guerra Nancy
Published: February 2021

Latinx families are increasing in the population in the United States and have documented mental health concerns. Much remains to be understood about mental health predictors within this population. The present study aimed to help fill this gap and offer an in‐depth assessment of psychopathology within a large (N = 330) sample of Latinx mothers and youth by exploring associations between sociodemographic risk, attachment relationship quality, and mental health. Demographic risk was not associated with youth or maternal psychopathology, but attachment relationship quality was associated with all indices of psychopathology in youth and mothers. The interaction between demographic risk and psychopathology only added to the prediction of maternal depression, revealing a pattern wherein maternal closeness was associated with lower depression at low and mean but not high levels of demographic risk. We discuss these findings in terms of the importance of supporting parent–child relationships in this population.
Dynamic right ventricular outflow tract obstruction by cardiac hydatic cysts: A multimodality imaging study
Authors: de Gregorio Cesare , Ferrazzo Giuseppe , Ceresa Fabrizio , De Donno Bruna Filomena , Patanè Francesco
Published: February 2021

We report the case of massive hydatic heart disease in a 50‐year‐old male patient referred to hospital for recent‐onset dyspnea, atypical chest, and hypotension. Right ventricular outflow tract obstruction was demonstrated to be caused by hypoechogenic formations at Doppler‐echocardiography and confirmed to be hydatic cysts at cardiac magnetic resonance. These cysts developed within the right ventricular wall and the septum, and caused hemodynamic instability.
Outcomes of 5000 pancreatectomies in Korean single referral center and literature reviews
Authors: Byun Yoonhyeong , Choi Yoo Jin , Han Youngmin , Kang Jae Seung , Kim Hongbeom , Kwon Wooil , Jang Jin‐Young
Published: February 2021

Background

Pancreatic resection has higher postoperative mortality and morbidity rates than other abdominal operations. Some centers have reported remarkable postoperative outcomes of minimally invasive surgery. This study investigated the chronological trends of pancreatectomies by analyzing a large‐scale database.

Methods

The medical records of 5175 patients who underwent pancreatic resection between 1961 and 2019 at a single institution were reviewed. To investigate the chronological change in survival outcomes of periampullary cancer, the survival data of 3,108 patients were analyzed.

Results

Patient age and the proportion with pancreatic cancer have increased over time. From 2015 to 2019, pancreatic cancer was the most common cause for resection (35.9%), followed by pancreatic cysts (24.8%) and common bile duct cancer (13.4%). The incidence of postoperative complications tended to decrease over time (26.0% from 2000 to 2004; 20.8% from 2015 to 2019). A comparison of survival outcomes of periampullary malignancies by period revealed that patients with pancreatic cancer significantly improved (5‐year survival rate: 14.4% before 2000% vs 15.2% from 2000 to 2009% vs 29.0% after 2009, P < .001).

Conclusions

Postoperative outcomes of pancreatic resection have improved over the past few decades. To improve outcomes in the future, an active multidisciplinary approach and postoperative management are required.
Predicting Neuroimaging Biomarkers for Antidepressant Selection in Early Treatment of Depression
Authors: Xue Li , Pei Cong , Wang Xinyi , Wang Huan , Tian Shui , Yao Zhijian , Lu Qing
Published: February 2021

Background

Due to the biological heterogeneity, 60%–70% of patients with major depressive disorder (MDD) do not respond to or achieve remission from first‐line antidepressants. Predicting neuroimaging biomarkers for early antidepressant treatment could guide initial antidepressant therapy.

Purpose

To assess for neuroimaging biomarkers for antidepressant selection in early antidepressant treatment.

Study Type

Prospective.

Subjects

A total of 85 MDD patients from the major site and 33 MDD patients from an out‐of‐sample test site.

Field Strength/Sequence

A 3.0 T, T1‐weighted imaging using a magnetization‐prepared rapid acquisition gradient‐echo sequence and diffusion tensor imaging (DTI) using an echo‐planar sequence.

Assessment

Baseline DTI data of patients who achieved early improvement after 2‐weeks of antidepressant treatment (selective serotonin reuptake inhibitors [SSRI] or serotonin‐norepinephrine reuptake inhibitors [SNRI]) were analyzed. An ensemble model was constructed using data from the major site and then applied to assess the early response of patients at the out‐of‐sample test site.

Statistical Tests

Support vector machine combined with leave‐one‐out cross‐validation were applied to construct the whole model from individual base models from different brain regions. Discriminative biomarkers were evaluated by calculating the changes in sensitivity and specificity obtained when removing a single base model from the whole model, the base model being removed changing in each run.

Results

Training performance over MDD patients at the major site achieved 75% accuracy while performance with accuracy of 70% was achieved in the out‐of‐sample test site. Assessing sensitivity and specificity changes following the removal of single base models from the prominent model highlighted the functions of two neural circuitries: SSRI‐related emotion regulation circuitry, centered on the hippocampus (sensitivity changes: 10%) and amygdala (sensitivity changes: 11%); and SNRI‐related emotion and reward circuitry, centered on the putamen (specificity changes: 8%) and orbital part of superior frontal gyrus (specificity changes: 12%).

Data Conclusion

These findings support future research on clinical antidepressant selection for MDD.

Evidence Level

1

Technical Efficacy

Stage 2
Comparison of Aptima and hybrid capture‐2 HPV tests and Pap test in the referral population in Japan
Authors: Kuroki Hiroko , Sakamoto Jinichi , Shibata Takeo , Takakura Masahiro , Sasagawa Toshiyuki
Published: February 2021

The Aptima human papillomavirus (HPV) test (APTIMA) detects E6‐E7 mRNA in abnormal cells in the uterine cervix. To investigate the accuracy of APTIMA for cervical cancer screening in Japan, 423 subjects, mostly referrals with abnormal cytology or being followed up for cervical intraepithelial neoplasia (CIN)1, were screened using two HPV tests, hybrid capture 2 (HC2) and APTIMA, and by the Pap test. Colposcopy was conducted in all subjects with a positive result in either test type. HPV genotyping was performed by Genosearch‐31.

A result of atypical squamous cells‐undetermined significance (ASC‐US) or worse on the HC2 test (ASC‐US‐HC2), and low‐grade squamous intraepithelial lesion (LSIL) or worse (LSIL+) on the Pap test, was regarded as positive. APTIMA (97.5%) was more sensitive than LSIL+ (85.1%) for detecting CIN2 or worse (CIN2+) (McNemar test; p = .0003), and more sensitive (98.6%) than ASC‐US‐HC2 (92.7%) for detecting CIN3+. APTIMA and HC2 had similar sensitivities. HPV genotyping revealed that CIN2/3 with high‐risk HPV (HR‐HPV) was overlooked in five cases by ASC‐US‐HC2, and in four cases by HC2, while no such lesions were missed by APTIMA. Thus, APTIMA might be superior to HC2 for primary HPV screening in Japan. One cancer case positive for HPV67 (potentially high risk, [pHR]) was overlooked by Pap test and both HPV tests, suggesting a need for a new HPV test able to detect pHR‐HPV types.
Mindfulness‐based stress reduction training modulates striatal and cerebellar connectivity
Authors: Santarnecchi Emiliano , Egiziano Eutizio , D’Arista Sicilia , Gardi Concetta , Romanella Sara M. , Mencarelli Lucia , Rossi Simone , Reda Mario , Rossi Alessandro
Published: February 2021

Mindfulness is a meditation practice frequently associated with changes in subjective evaluation of cognitive and sensorial experience, as well as with modifications of brain activity and morphometry. Aside from the anatomical localization of functional changes induced by mindfulness practice, little is known about changes in functional and effective functional magnetic resonance imaging (fMRI) connectivity. Here we performed a connectivity fMRI analysis in a group of healthy individuals participating in an 8‐week mindfulness‐based stress reduction (MBSR) training program. Data from both a “mind‐wandering” and a “meditation” state were acquired before and after the MBSR course. Results highlighted decreased local connectivity after training in the right anterior putamen and insula during spontaneous mind‐wandering and the right cerebellum during the meditative state. A further effective connectivity analysis revealed (a) decreased modulation by the anterior cingulate cortex over the anterior portion of the putamen, and (b) a change in left and right posterior putamen excitatory input and inhibitory output with the cerebellum, respectively. Results suggest a rearrangement of dorsal striatum functional and effective connectivity in response to mindfulness practice, with changes in cortico‐subcortical‐cerebellar modulatory dynamics. Findings might be relevant for the understanding of widely documented mindfulness behavioral effects, especially those related to pain perception.
USP39 mediates p21‐dependent proliferation and neoplasia of colon cancer cells by regulating the p53/p21/CDC2/cyclin B1 axis
Authors: Yuan Jiahui , Li Xiaomei , Zhang Gongye , Cheng Weipeng , Wang Weiwei , Lei Yongbin , Ma Qiujuan , Song Gang
Published: February 2021

Ubiquitin‐specific protease 39 (USP39) is frequently overexpressed in a variety of cancers, and involved in the regulation of various biological processes, such as cell proliferation, cell cycle progression, apoptosis and pre‐messenger RNA splicing. Nevertheless, the biological roles and mechanisms of USP39 in colon cancer remain largely unknown. In this study, we analyzed whether USP39 can be a molecular target for the treatment of colon cancer. Whilst overexpression of USP39 was detected in human colon cancer tissues and cell lines, USP39 knockdown was observed to inhibit the growth and subcutaneous tumor formation of colon cancer cells. Further analysis showed that USP39 knockdown can stabilize p21 by prolonging the half‐life of p21 and by upregulating the promoter activity of p21. The RS domain and USP domain of USP39 were found to play an essential role. Additionally, our findings revealed that USP39 plays a regulatory role in the proliferation of colon cancer cells by the p53/p21/CDC2/cyclin B1 axis in a p21‐dependent manner. Taken together, this study provided the theoretical basis that may facilitate the development of USP39 as a novel potential target of colon cancer therapy.
Are Alberta’s Northern Pike Populations at Risk from Walleye Recovery?
Authors: Paul Andrew J. , Cahill Christopher L. , MacPherson Laura , Sullivan Michael G. , Brown Myles R.
Published: February 2021

Angling catch rates of Walleye Sander vitreus in many lakes across Alberta have increased dramatically in the past 20 years, following their collapse and then recovery after implementation of restrictive harvest regulations. With increased abundance, some anglers are concerned that Walleyes may negatively affect abundance of Northern Pike Esox lucius. To address this hypothesis, we looked at net catch data for each species from 352 surveys in 129 lakes across Alberta between 2000 and 2017. Results were equivocal. Netting data indicated that low-density Northern Pike populations were not associated with high densities of Walleyes when grouped categorically. However, mixed-model quantile regression did support a negative relationship for the two species, but the mechanism is unclear and the strength of the interaction is weak in most cases. In few lakes (≤10%), potentially acceptable reductions in Walleye densities may produce meaningful increases in Northern Pike but uncertainty is substantial. Future Walleye harvest experiments to reduce uncertainty and establish causation are warranted only if Northern Pike are already at moderate to high densities and large reductions in Walleyes (≥75%) are acceptable. For these reasons, increased Walleye harvest is not supported as a management tool for increasing Northern Pike populations or enhancing angler catch rates in Alberta.
Preclinical study testing feasibility and technical requirements for successful telerobotic long distance peripheral vascular intervention
Authors: Legeza Peter , Sconzert Kalyna , Sungur John‐Michael , Loh Thomas M. , Britz Gavin , Lumsden Alan
Published: February 2021

Background

Robotic‐assisted endovascular surgery enables us to perform interventions from long distances. This study evaluates the workflow and telecommunication requirements of telerobotic peripheral vascular interventions.

Methods

Ten superficial femoral artery cases were performed by the operator being 44 miles away from the interventional suite, with an endovascular robotic system, on a high‐fidelity endovascular simulator. Procedural success, technical success, fluoroscopy time, residual stenosis, contrast dose and network delay were registered. Communication success was assessed after each procedure on a scale from 1 (unacceptable) to 5 (ideal).

Results

Procedural success and technical success were 100% and 80%, respectively. The mean residual stenosis, fluoroscopy time and contrast dose were 1.7 ± 5.25%, 6.5 ± 1.8 min and 58.8 ± 14.8 ml. The mean network latency was 38.9 ± 3.5 ms. Median communication success scores were 4.5 (min: 4, max: 5) reported by both the operator and the bedside technician on a scale of 1 (unacceptable) to 5 (ideal).

Conclusion

With a stable network connection and good communication protocol, a high success rate was achieved for remote robotic‐assisted peripheral vascular intervention in an ex vivo model.