bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of ultrasound‐assisted catheter‐directed thrombolysis for submassive pulmonary embolism: A meta‐analysis of case series
Authors: Wu Jiayan , Chen Haiming , Yu Yongqin , Peng Lingsheng , Li Jieying , Liang Hengrui , Ba Manqing , Ruan Honglian , Hong Cheng
Published: January 2020

Background

During the past few years, there has been a surge in the use of ultrasound‐assisted catheter‐directed thrombolysis (UACDT) for submassive pulmonary embolism (SPE). However, few studies evaluated the feasibility of UACDT for SPE.

Purpose

To evaluate the feasibility of UACDT in treating SPE.

Methods

A comprehensive search of online databases was performed. Search terms UACDT in SPE were entered into PubMed, Embase, Scopus and the Cochrane Library to identify related articles published until October 2018. A quality assessment and data extraction were performed by two researchers. Meta‐analysis was performed using R statistical software.

Results

Twelve studies with 485 patients were included in this meta‐analysis. The pooled right ventricular/left ventricular ratio decrease and pulmonary artery systolic pressure drop after treatment was −0.34 (95% CI: −0.43, −0.25) and −15.05 (95% CI: −18.10, −12.00) mm Hg, respectively. The pooled major bleeding rate was 1.0% (95% CI: 0.0%, 3.0%), and the in‐hospital mortality was 0.0% (95% CI: 0.0%, 1.0%).

Conclusion

This up to data meta‐analysis confirms that UACDT is a feasible treatment for SPE.
A technique for the translocation of ant colonies and termite mounds to protect species and improve restoration efforts
Authors: King Timothy J. , Balfour Julia
Published: January 2020

Ant colonies or termite mounds, particularly of rare species, sometimes require translocation for conservation of the species and their associated fauna. Translocations often increase the species richness of the receptor habitat. A wide range of appropriate grabs, causing least colony disturbance, can be fitted to maneuverable compact loaders. Compact loaders allow rapid nest transport between donor and receptor sites. We discuss the advantages of this technique. In this case a tree spade attached to a compact loader was used to rapidly insert occupied Lasius flavus ant‐hills into a recipient site 1 km away. The colonies had all survived 18 months later despite two lengthy droughts.
Socio‐economic status and mortality in people with type 1 diabetes in Scotland 2006–2015: a retrospective cohort study
Authors: Campbell R. A. S. , Colhoun H. M. , Kennon B. , McCrimmon R. J. , Sattar N. , McKnight J. , Wild S. H ,   Scottish Diabetes Research Network Epidemiology Group
Published: January 2020

Aims

To describe the association between socio‐economic status and mortality in a nation‐wide cohort of people with type 1 diabetes in Scotland and to compare patterns over time and with the general population.

Methods

A retrospective cohort study was performed using data for people with type 1 diabetes from a population‐based register linked to mortality records. Socio‐economic status was derived from quintiles of an area‐based measure: the Scottish Index of Multiple Deprivation. Sex‐specific directly age‐standardized mortality rates for each Scottish Index of Multiple Deprivation quintile and rate ratios comparing the most vs least deprived quintile were calculated for two time periods: 2006–2010 and 2011–2015. Data for the population without type 1 diabetes between 2011 and 2015 were available for comparison.

Results

Data for 3802 deaths among 33 547 people with type 1 diabetes were available. The age‐standardized mortality rate per 1000 person‐years decreased over time (from 2006–2010 to 2011–2015) for men and women with type 1 diabetes: 24.8 to 20.2 and 22.5 to 17.6, respectively. Mortality in populations with and without type 1 diabetes was generally higher for men than women and was inversely associated with socio‐economic status. Rate ratios for the most vs least deprived groups increased over time among people with type 1 diabetes (men: 2.49 to 2.81; women: 1.92 to 2.86) and were higher than among populations without type 1 diabetes in 2011–2015 (men: 2.06; women: 1.66).

Conclusions

Socio‐economic deprivation was associated with a steeper mortality gradient in people with type 1 diabetes than in the population without type 1 diabetes in Scotland. Age‐standardized mortality has decreased over time but socio‐economic inequalities may be increasing.
Non‐attendance at diabetes outpatient appointments: a systematic review
Authors: Brewster S. , Bartholomew J. , Holt R. I. G. , Price H.
Published: January 2020

Background

Non‐attendance at diabetes outpatient appointments is a sizeable problem worldwide and has been associated with suboptimal health outcomes. We aimed to describe the characteristics, health outcomes and reasons given for non‐attendance at doctor‐ or nurse‐led diabetes appointments, and interventions to improve attendance.

Methods

PubMed, EMBASE, CINAHL and PsychInfo were searched from database inception to February 2019. Included articles were peer‐reviewed, published in English, related to adults or young people with type 1 or type 2 diabetes, and addressed one of the above aspects of non‐attendance. Studies were excluded if reporting on other types of diabetes or reviewing attendance at structured education, retinal screening, paediatric, antenatal, podiatry or dietetic clinics.

Results

Thirty‐four studies of varied designs were identified (15 observational, 1 randomized control trial, 9 qualitative, 5 surveys, 4 service improvements). The definition of non‐attendance varied. Younger adults, smokers and those with financial pressures were less likely to attend. Non‐attendance was associated with higher HbA1c; other outcomes were varied but typically worse in non‐attenders. Reasons for non‐attendance in qualitative studies fell into three categories: balancing the costs and benefits of attendance, coping strategies, and the relationships between the person with diabetes and healthcare professionals. Interventions included appointment management strategies, service improvements, patient navigators and WebCam appointments.

Conclusions

Non‐attendance is only partially explained by logistical issues. Qualitative studies suggest complex psychosocial factors are involved. Interventions have progressed from simple appointment reminders in an attempt to address some of the psycho‐social determinants, but more work is needed to improve attendance.
Racism en Route
Authors: Maluleke Tinyiko
Published: January 2020

This article argues that in Africa, the nature and advent of racism has to be traced back to the earliest encounters between Africans and Europeans, including the first seven centuries but especially during the slavery and colonial eras. Religion (notably Islam and Christianity), trade, education, culture, and “science” were important incubators and justifiers of racism, in earlier as well as recent times. The paper concludes by proposing some ways in which African theology can stay agile and keep pace with the resilient and adaptive forms of racism in contemporary Africa.
Racial Justice for the Windrush Generation in Great Britain
Authors: Reddie Anthony G.
Published: January 2020

This article argues that the experience of the “Windrush generation,” Black Caribbean post–Second World War migrants to the UK, has been one of constant struggle for racial justice. Living in Britain has been undertaken against the backdrop of a Mission Christianity that has exuded a distinct anti‐Blackness in its relationship with Black bodies across four centuries. This particular dynamic of “Christian Britain” has created a framework that has helped to shape the agency of Black bodies, essentially marking them as “less than.” This theo‐cultural framework has led to a racialized existence for Black British people of the Windrush generation and their descendants. The Christianity that has emerged from the Black Caribbean experience constantly challenges White British Christianity to express an anti‐racist and more inclusive model of liberative praxis. This paper is written against the backdrop of the Brexit furore in Britain and the xenophobia and rise in racist attacks that have underpinned the rise in White British nationalism.
Sagittal plane slab fractures of the third carpal bone in 45 racing Thoroughbred horses
Authors: Tallon Rose , O’Neill Henry , Bladon Bruce
Published: January 2020

Background

Sagittal plane slab fractures of the third carpal bone are a recognised injury in the racehorse. Currently no published data exist for the UK Thoroughbred racehorse population.

Objectives

To document return to racing following sagittal slab fracture of the third carpal bone in a UK‐based racehorse population, and to compare conservative and surgical management.

Study design

Single centre retrospective study.

Methods

Computerised medical and racing records were searched over a 15‐year period for Thoroughbred racehorses with a simple sagittal slab fracture of the third carpal bone. Horses with comminuted fractures and short incomplete linear lucencies were excluded. Time from intervention to next race was recorded. Success rates were compared by Fisher's Exact Test and Mann‐WhitneyUTest.

Results

Forty‐seven horses, with 49 fractures met the inclusion criteria. Overall, 27 horses raced following injury (60%). Median time to first start was 251 days (115‐600, IQR 109). Fifteen horses with 16 fractures were managed conservatively. Seven horses (47%) raced, 115‐508 days following injury (median 240 days, IQR 306). Thirty horses underwent surgery; this involved placement of a single 3.5‐mm lag screw under arthroscopic guidance. Twenty horses (67%) raced again 145‐600 days following surgery (median 264 days, IQR 102). A higher proportion of horses managed surgically improved their Racing Post Rating (RPR) following injury (14/20), compared with those managed conservatively (1/7,P = .02).

Main limitations

The numbers of horses are small, particularly for those managed conservatively. Treatment was not randomly allocated, and as such several horses which underwent conservative management were subsequently retired for breeding.

Conclusions

This case series indicates that both arthroscopic repair and conservative management of sagittal slab fractures of the third carpal bone allows horses to successfully return to training and racing.
Changing how we approach fisheries: A first attempt at an operational framework for ecosystem approaches to fisheries management
Authors: Link Jason S. , Huse Geir , Gaichas Sarah , Marshak Anthony R.
Published: January 2020

The increasing need to account for the many factors that influence fish population dynamics, particularly those external to the population, has led to repeated calls for an ecosystem approach to fisheries management (EAFM). Yet systematically and clearly addressing these factors, and hence implementing EAFM, has suffered from a lack of clear operational guidance. Here, we propose 13 main factors (shift in location, migration route or timing, overfishing (three types), decrease in physiology, increase in predation, increase in competition, decrease in prey availability, increase in disease or parasites and a decline in habitat quality or habitat quantity) that can negatively influence fish populations via mechanisms readily observable in ~20 population features. Using these features as part of a diagnostic framework, we develop flow charts that link probable mechanism(s) underlying population change to the most judicious management actions. We then apply the framework for example case studies that have well‐known and documented population dynamics. To our knowledge, this is the first attempt to provide a clearly defined matrix of all the probable responses to the most common factors influencing fish populations, and to examine possible diagnostics simultaneously, comparatively and relatively in an attempt to elucidate the most probable mechanisms responsible. The framework we propose aims to operationalize EAFM, thereby not only better diagnosing factors influencing fish populations, but also suggesting the most appropriate management interventions, and ultimately leading to improved fisheries. We assert the framework proposed should result in both better use of limited analytical and observational resources and more tailored and effective management actions.
GPER‐mediated, oestrogen‐dependent visceral hypersensitivity in stressed rats is associated with mast cell tryptase and histamine expression
Authors: Xu Shaoxian , Wang Xiaoyan , Zhao Jing , Yang Suzhen , Dong Lei , Qin Bin
Published: January 2020

Visceral hypersensitivity (VH) is common in irritable bowel syndrome (IBS), and female patients are more likely to seek healthcare services for IBS‐related abdominal pain. Oestrogen has been reported to mediate pain modulation via its receptor, and mast cells are known to participate in the development of visceral hypersensitivity. Our previous studies showed that the G‐protein‐coupled oestrogen receptor (GPER, also known as GPR30) was expressed by mast cells in human colonic tissues and was associated with IBS type and severity of visceral pain. However, whether GPER is involved in oestrogen‐dependent visceral hypersensitivity via mast cell degranulation is still unknown. Rats were subjected to wrap partial restraint stress to induce visceral hypersensitivity and were ovariectomized (OVX) to eliminate the effects of oestrogen on visceral hypersensitivity. OVX rats were treated with oestrogen, an oestrogen receptor α and β antagonist (ICI 182.780), a GPER antagonist (G15) or a GPER agonist (G1), to evaluate the effects of oestrogen via its receptor. The colorectal distention test was performed to assess visceral sensitivity. Immunofluorescence studies were performed to evaluate GPER and mast cell tryptase co‐expression. Mast cell number with degranulation was detected by specific staining. Mast cell tryptase expression in rat colon was also investigated by Western blot and immunohistochemistry. Substance P and histamine expression were examined by ELISA. GPER was expressed by the majority of tryptase‐positive mast cells in the colonic mucosa. Stressed rats showed increased visceral sensitivity, increased mast cell degranulation, mast cell tryptase expression, and increased colon histamine levels. Ovariectomy reduced stress‐induced VH in female rats and decreased mast cell degranulation, mast cell tryptase expression, and histamine levels, whereas oestrogen replacement reversed these effects. In OVX rats, the GPER antagonist G15 counteracted the enhancing effects of oestrogen on stress‐induced VH, mast cell degranulation, mast cell tryptase, and histamine expression, whereas VH was preserved after treatment with ICI 182.780. On the other hand, pretreatment with the selective GPER agonist G1 at doses between 1 and 20 μg/kg significantly increased VH, mast cell tryptase, and histamine expression in OVX‐stressed rats, mimicking the effects of oestrogen. GPER plays a pivotal role in the regulation of mast cell degranulation, mast cell tryptase expression, and histamine levels and contributes to the development of colonic hypersensitivity in a female rat model of IBS.
Factors influencing the abundance of three common nearshore fishes in south‐west Lake Michigan
Authors: Stacy‐Duffy William L. , Thomas Sara M. , Wahl David H. , Czesny Sergiusz J.
Published: January 2020

Variation in the distribution and abundance of nearshore fishes is critical to understand food web processes and fishery management issues in Lake Michigan. This study characterised patterns in abundance of three common nearshore species, yellow perch Perca flavescens (Mitchell), round goby Neogobius melanostomus (Pallas) and alewife Alosa pseudoharengus (Wilson), in relation to spatio‐temporal, abiotic and biotic factors using gillnet sampling conducted across 5 years at multiple locations representing different substrates. Significant variations were observed in alewife and round goby catches between locations. A negative relationship between round goby and age‐0 yellow perch catch was observed, indicating potential competition between the two species. This study demonstrates that variability in nearshore fish communities can be driven by factors including substrate and interspecific interactions. Given the prominent role these species play in Lake Michigan's food web and thus their importance to fishery production, a thorough understanding of these factors is warranted.
Struggles for distinction: Classing as discursive process in UK museum work
Authors: Evans Samantha , Whiting Rebecca , Mackenzie Davey Kate
Published: January 2020

This article responds to calls from critical diversity scholars to explore class in context, arguing for a view of classing as a discursive process and adopting Bourdieu's concept of field as a site of discursive struggle. Analysing interview, web and focus group data, we address this in the field of UK museum work. We contextualize the field's dynamic nature, highlighting its state of flux and explore three discourses: distinguishing the field; disavowing the market; and gaining recognition through which it is constituted, and classing practised. Discursive strategies of reinforcing, reframing and re‐valorizing were deployed by participants to legitimate their own and other positions in the field. We show how classing is a core process constituting an occupational field, how museum workers are entrapped by and complicit in this process, and conclude with wider implications for understandings of class, classed inequality and diversity.
Current state of play regarding dental extractions in patients with haemophilia: Consensus or evidence‐based practice? A review of the literature
Authors: Bajkin Branislav , Dougall Alison
Published: January 2020

Due to the global prevalence of oral disease, tooth extraction is the most common surgical procedure required in general population thus likely to be similarly common in patients with haemophilia, especially those in older age and those living in countries with restricted resources. There are little or no consensus about optimal level and duration of factor replacement (FRP) therapy required to prevent bleeding complication following surgery and low levels of evidence to inform protocols and guidelines. The goal of this article was to review the literature regarding haematological treatment protocols and to assess their effectiveness in prevention of bleeding complications during and after tooth extractions in people with haemophilia. A total number of 29 articles were identified. Only two of the studies were randomized controlled trials, and meta‐analysis was not possible. Significant heterogeneity regarding haematological regimes, dental surgical procedures, disease severity and sample size of published studies which are unable to reliably inform the provision of safe dental surgery was noted. Based on the haematological regimens, all studies were classified into one of three groups: pre‐ and postoperative FRP or DDAVP, single preoperative FRP or DDAVP, and no FRP treatment. The overall reported bleeding rate in case of both pre‐ and postoperative FRP and single dose FRP preoperative is similar, 11.9% and 11.4%, respectively, indicating that minimizing the use of clotting factor concentrate is possible if proper local haemostatic measures are provided. Strictly designed prospective studies with higher number of patients are necessary to get firm conclusions about optimal FRP treatment required to prevent bleeding complications during and after oral surgery in patients with haemophilia.
Familial “Diplegic” Migraine – Description of a Family With a Novel CACNA1A Mutation
Authors: Sprouse Blum Adam S. , Couperus Cody J. , Rosen Brian J. , Haskin‐Leahy Leanne F. , Shapiro Robert E.
Published: January 2020

Objective

To characterize phenotypes of a novel CACNA1A mutation causing familial hemiplegic migraine type 1.

Background

Familial hemiplegic migraine is a rare monogenic form of migraine associated with attacks of fully reversible unilateral motor weakness. We now report a novel CACNA1A gene mutation associated with fully reversible bilateral motor weakness (diplegia).

Methods

The proband underwent genotyping which identified a novel CACNA1A missense mutation (c.622 [isoform 1] G > A [p.Gly208Arg]). To characterize phenotypes associated with this novel mutation, the proband and 8 of her similarly affected family members underwent a semi‐structured interview.

Results

All 9 subjects who were interviewed met ICHD‐3 phenotypic diagnostic criteria for FHM, including reporting attacks with reversible unilateral motor weakness. Additionally, 7 of 9 subjects reported attacks including reversible motor weakness affecting both sides of the body simultaneously.

Conclusions

We describe a novel CACNA1A mutation associated with migraine attacks including reversible diplegia.
The Risks or Lack Thereof of Migraine Treatments in Vascular Disease
Authors: Diener Hans‐Christoph
Published: January 2020

Premises

Patients with migraine have a co‐morbidity with vascular diseases such as hypertension, coronary heart disease, and stroke.

Problem

This overview gives recommendations for the therapy of acute migraine attacks and for migraine  prevention in patients with vascular diseases. In particular, the use of triptans in patients with vascular diseases is discussed.

Potential Solutions

Currently, there is a contraindication for the use of the triptans in patients with vascular disease, although there is no evidence that triptans increase the risk of heart attacks or stroke.
Improved corrosion resistance of Al2O3‐SiC‐C castables through in situ carbon containing aluminate cement as binder
Authors: Yang Shoulei , Xiao Guoqing , Ding Donghai , Yu Xinmin , Guan Li , Gao Jianying
Published: January 2020

Slag corrosion is one of the main damage modes for refractory castables used in iron and steel metallurgy. The matrix plays vital roles for corrosion resistance of refractory castables. In the present paper, the properties of the Al2O3‐SiC‐C‐based trough castables with in situ carbon containing calcium aluminate cement (CCAC) and ball pitch as carbon sources, respectively, were comparatively investigated. The microstructures of the trough castables after corrosion were observed by field‐emission scanning electron microscopy. The results showed that after being corroded at 1450°C for 3 hours, the corrosion depth of Al2O3‐SiC‐C‐castables with CCAC as binder (A2) was 1.2 mm, 65.71% lower than that of the trough castables with ball pitch as carbon source (A1), though the content of carbon materials in the former was much lower than that of the latter. The reasons for these observations were that the in situ carbon materials of CCAC exhibit improved distribution in the matrices of castables and excellent oxidation resistance, resulting in lower porosity within the castables, and hindered the penetration of the molten slag at high temperatures. In addition, the Al2O3‐SiC‐C‐castables bonded by CCAC displayed good mechanical properties at room temperature and elevated temperature.
Dual–class ownership structure and audit fees
Authors: Lobanova Olesya , Mishra Suchismita , Raghunandan Kannan , Aidov Alexandre
Published: January 2020

A dual‐class share structure creates a separation between cash flow rights and voting rights. Dual‐class firms impact audit fees through their effect on supply/demand for auditing. This article examines the association between audit fees and dual‐class share structure for U.S. public firms. We find that a dual‐class share structure is associated with lower audit fees compared to single‐class firms. Further, within dual‐class firms, we find that the divergence between cash flow rights and voting rights is negatively associated with audit fees. The results are consistent with the managerial incentive‐alignment effect and/or the insulation effect of a dual‐class share structure on the supply/demand for audit services. This study highlights that the ownership structure of a firm constitutes an important role in audit pricing.
Thermodynamic descriptions of the light rare‐earth elements in silicon carbide ceramics
Authors: Xu Kai , Chang Keke , Zhou Xiaobing , Chen Leilei , Liu Junwen , Deng Zixuan , Huang Feng , Huang Qing
Published: January 2020

The Y3Si2C2 coating on the silicon carbide (SiC) powders is reported to improve the sintering process, but the relatively high sintering temperature (1600°C) restricts the engineering application. A series of thermodynamic descriptions for the SiC with light rare‐earth elements are desired to develop potential SiC‐RE3Si2C2 core‐shell structures as sintering aids with lower temperatures. Coupling the CALPHAD (CALculation of PHAse Diagram) approach and first‐principles calculations, we have investigated the RE‐Si‐C (RE = La, Ce and Pr) systems. In the SiC‐RE3Si2C2 core‐shell structures, the RE3Si2C2 phases can react with SiC via ternary eutectic reactions at 810°C, 747°C, and 1148°C respectively. The predicted thermal behaviors of the Pr3Si2C2 phase were further confirmed by our key experiments. Therefore, our database can be used to predict promising sintering aids and guide the subsequent processes.
Do bigger bodies require bigger radiators? Insights into thermal ecology from closely related marine mammal species and implications for ecogeographic rules
Authors: Adamczak Stephanie K. , Pabst D. Ann , McLellan William A. , Thorne Lesley H.
Published: January 2020

Aim

The aim of this study was to determine if marine mammals follow ecogeographic rules. We examined Bergmann's rule and Allen's rule in two pilot whale species with contrasting latitudinal distributions.

Location

Northwest Atlantic Ocean.

Taxon

Globicephala spp.

Methods

We analysed morphometric data collected from strandings of short‐ and long‐finned pilot whales in the Northwest Atlantic Ocean to assess intraspecific and interspecific variation in surface area to volume ratios (SA:V) of the body core and appendage surface area relative to body core SA (normalized appendage SA) using a novel 3D modelling method.

Results

Our results suggest that ecogeographic variation in morphometrics between the two pilot whale species is consistent with morphological adaptations required to balance heat conservation and heat dissipation. Interspecific differences in morphology supported Bergmann's rule for fully grown individuals: the more temperate long‐finned pilot whale had a larger body size and lower body core SA:V than the short‐finned pilot whale, which has a more tropical distribution. Allen's rule was not supported; when all appendages were considered together, long‐finned pilot whales had larger normalized SA than short‐finned pilot whales. However, the pectoral flippers were the primary driver of this relationship; while long‐finned pilot whales had proportionally larger pectoral flippers, short‐finned pilot whales had proportionally larger dorsal fins and flukes. In addition, larger long‐finned pilot whales (i.e. males and mature individuals) had proportionally larger pectoral flippers than smaller long‐finned pilot whales.

Main Conclusions

Pilot whales follow Bergmann's rule but do not follow Allen's rule when fully mature. Thinly insulated appendages in marine mammals can be used to dissipate heat as the core warms, and larger and better insulated marine mammals may require relatively larger appendages in order to offload heat and thermoregulate effectively. Our results provide novel insight into ecogeographic rules and suggest that species in higher latitude climates towards the poles will demonstrate tradeoffs between core body heat conservation and appendage heat dissipation.
Silencing of LINC00461 enhances radiosensitivity of lung adenocarcinoma cells by down‐regulating HOXA10 via microRNA‐195
Authors: Hou Jiqiu , Wang Yanjun , Zhang Hongmei , Hu Yuxin , Xin Xiuqin , Li Xiaodan
Published: January 2020

Lung adenocarcinoma is recognized as one of the most recurrent tumours in adults. Long non‐coding RNAs (lncRNAs) are non–protein‐coding transcripts and have been demonstrated to regulate biological functions during tumorigenesis. Our study aims to investigate the underlying molecular mechanisms of LINC00461/microRNA‐195 (miR‐195)/HOXA10 responsible for its involvement in lung adenocarcinoma. We firstly selected differentially expressed lncRNAs and genes by the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO). The functional role of LINC00461 in lung adenocarcinoma was then determined using ectopic expression, knockdown and reporter assay experiments. Besides, we detected the expression profiles of LINC00461, miR‐195, HOXA10 and apoptosis‐ and invasion‐related genes. Cell proliferation, migration and invasion were evaluated. In vivo tumour formation ability was analysed. Overexpressed LINC00461 and HOXA10 but down‐regulated miR‐195 were observed in primary and metastatic lung adenocarcinoma. LINC00461 negatively regulated miR‐195, while miR‐195 negatively regulated HOXA10. Forced LINC00461 expression decreased expression of miR‐195 and Bax, increased expression of HOXA10, MMP‐2, MMP‐9 and Bcl‐2, promoted cell proliferation, migration and invasion as well as tumour formation, and enhanced radiosensitivity of lung adenocarcinoma cells. However, these effects were reversed by lentivirus‐mediated miR‐195–forced expression, thereby suggesting that miR‐195 could antagonize the harmful effect of LINC00461 on lung adenocarcinoma cells. Collectively, the present study provides evidence supporting the inhibitory effect of LINC00461 silencing on lung adenocarcinoma, which suppresses lung adenocarcinoma cell migration, invasion and radiosensitivity via HOXA10 by binding to miR‐195, which provides a promising basis for the targeted intervention treatment for human lung adenocarcinoma.
Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST‐segment elevation myocardial infarction
Authors: Bøtker Hans Erik , Cabrera‐Fuentes Hector Alejandro , Ruiz‐Meana Marisol , Heusch Gerd , Ovize Michel
Published: January 2020

Pre‐clinical studies have indicated that mitoprotective drugs may add cardioprotection beyond rapid revascularization, antiplatelet therapy and risk modification. We review the clinical efficacy of mitoprotective drugs that have progressed to clinical testing comprising cyclosporine A, KAI‐9803, MTP131 and TRO 40303. Whereas cyclosporine may reduce infarct size in patients undergoing primary angioplasty as evaluated by release of myocardial ischaemic biomarkers and infarct size imaging, the other drugs were not capable of demonstrating this effect in the clinical setting. The absent effect leaves the role of the mitochondrial permeability transition pore for reperfusion injury in humans unanswered and indicates that targeting one single mechanism to provide mitoprotection may not be efficient. Moreover, the lack of effect may relate to favourable outcome with current optimal therapy, but conditions such as age, sex, diabetes, dyslipidaemia and concurrent medications may also alter mitochondrial function. However, as long as the molecular structure of the pore remains unknown and specific inhibitors of its opening are lacking, the mitochondrial permeability transition pore remains a target for alleviation of reperfusion injury. Nevertheless, taking conditions such as ageing, sex, comorbidities and co‐medication into account may be of paramount importance during the design of pre‐clinical and clinical studies testing mitoprotective drugs.
Dracorhodin perchlorate inhibits osteoclastogenesis through repressing RANKL‐stimulated NFATc1 activity
Authors: Liu Yuhao , Wang Ziyi , Ma Chao , Wei Zhenquan , Chen Kai , Wang Chao , Zhou Chi , Chen Leilei , Zhang Qingwen , Chen Zhenqiu , He Wei , Xu Jiake
Published: January 2020

Osteolytic skeletal disorders are caused by an imbalance in the osteoclast and osteoblast function. Suppressing the differentiation and resorptive function of osteoclast is a key strategy for treating osteolytic diseases. Dracorhodin perchlorate (D.P), an active component from dragon blood resin, has been used for facilitating wound healing and anti‐cancer treatments. In this study, we determined the effect of D.P on osteoclast differentiation and function. We have found that D.P inhibited RANKL‐induced osteoclast formation and resorbed pits of hydroxyapatite‐coated plate in a dose‐dependent manner. D.P also disrupted the formation of intact actin‐rich podosome structures in mature osteoclasts and inhibited osteoclast‐specific gene and protein expressions. Further, D.P was able to suppress RANKL‐activated JNK, NF‐κB and Ca2+ signalling pathways and reduces the expression level of NFATc1 as well as the nucleus translocation of NFATc1. Overall, these results indicated a potential therapeutic effect of D.P on osteoclast‐related conditions.
Artificial neural networks allow response prediction in squamous cell carcinoma of the scalp treated with radiotherapy
Authors: Damiani G. , Grossi E. , Berti E. , Conic R.R.Z. , Radhakrishna U. , Pacifico A. , Bragazzi N.L. , Piccinno R. , Linder D.
Published: January 2020

Background

Epithelial neoplasms of the scalp account for approximately 2% of all skin cancers and for about 10–20% of the tumours affecting the head and neck area. Radiotherapy is suggested for localized cutaneous squamous cell carcinomas (cSCC) without lymph node involvement, multiple or extensive lesions, for patients refusing surgery, for patients with a poor general medical status, as adjuvant for incompletely excised lesions and/or as a palliative treatment. To date, prognostic risk factors in scalp cSCC patients are poorly characterized.

Objective

To identify patterns of patients with higher risk of postradiotherapy recurrence.

Methods

A retrospective observational study was performed on scalp cSCC patients with histological diagnosis who underwent conventional radiotherapy (50–120 kV) (between 1996 and 2008, follow‐up from 1 to 140 months, median 14 months). Out of the 79 enrolled patients, 22 (27.8%) had previously undergone a surgery. Two months after radiotherapy, 66 (83.5%) patients achieved a complete remission, 6 (7.6%) a partial remission, whereas 2 (2.5%) proved non‐responsive to the treatment and 5 cases were lost to follow‐up. Demographical and clinical data were preliminarily analysed with classical descriptive statistics and with principal component analysis. All data were then re‐evaluated with a machine learning‐based approach using a 4th generation artificial neural networks (ANNs)‐based algorithm.

Results

Artificial neural networks analysis revealed four scalp cSCC profiles among radiotherapy responsive patients, not previously described: namely, (i) stage T2 cSCC type, aged 70–80 years; (ii) frontal cSCC type, aged <70 years; (iii) non‐recurrent nodular or nodulo‐ulcerated, stage T3 cSCC type, of the vertex and treated with >60 Grays (Gy); and (iv) flat, occipital, stage T1 cSCC type, treated with 50–59 Gy. The model uncovering these four predictive profiles displayed 85.7% sensitivity, 97.6% specificity and 91.7% overall accuracy.

Conclusions

Patient profiling/phenotyping with machine learning may be a new, helpful method to stratify patients with scalp cSCCs who may benefit from a RT‐treatment.
Geriatric Conditions Predict Discontinuation of Anticoagulation in Long‐Term Care Residents With Atrial Fibrillation
Authors: Kapoor Alok , Foley Gray , Zhang Ning , Zhou Yanhua , Crawford Sybil , McManus David , Gurwitz Jerry
Published: January 2020

BACKGROUND

Anticoagulation (AC) for stroke prevention in long‐term care (LTC) residents with atrial fibrillation (AF) involves a challenging risk‐benefit evaluation. We measured the association of geriatric conditions with discontinuation of AC.

DESIGN

Retrospective cohort analysis.

SETTING

LTC facilities across the United States.

PARTICIPANTS

A total of 48 545 individuals residing in LTC facilities in 2015 with AF and sufficient information to establish their status as someone who stopped AC vs someone who continued AC.

MEASUREMENTS

We measured the association of six geriatric conditions—recent fall, severe activity of daily living (ADL) dependency (21‐28 on a 28‐point scale), mobility impairment, cognitive impairment, body mass index (BMI) less than 18.5 kg/m2, and weight loss (≥5% in 1 month or ≥10% in 6 months)—with discontinuation of AC. To identify cases of discontinuation, we required a pattern of being on AC over two consecutive recordings of the Minimum Data Set, the nursing home quality control data set recorded every 90 days, followed by two assessments being off AC—pattern of “on‐on‐off‐off.” By contrast, we required a pattern of “on‐on‐on‐on” for continuers. We then constructed six logistic regression models to measure the independent association between each geriatric condition and discontinuation of AC, adjusted for CHA2DS2‐VASc stroke risk score, recent bleeding hospitalization, and other confounders.

RESULTS

There were 4172 discontinuers and 44 373 continuers. Recent fall predicted a 1.9‐fold increase in the odds of discontinuation (odds ratio = 1.91; 95% confidence interval = 1.66‐2.20), whereas mobility and cognitive impairment only increased the odds by 14% to 17%. Severe ADL dependency, BMI less than 18.5 kg/m2, and weight loss of 10% each increased odds of discontinuation by 55% to 68%. CHA2DS2‐VASc score did not predict discontinuation.

CONCLUSION

Several geriatric conditions predicted discontinuation of AC, whereas CHA2DS2‐VASc score did not. Future research should examine the association of geriatric conditions and discontinuation of warfarin discrete from newer anticoagulants and association of geriatric conditions with development of stroke and bleeding. J Am Geriatr Soc 68:717–724, 2020
Effects of a nutrient‐dense formula compared with a post‐discharge formula on post‐discharge growth of preterm very low birth weight infants with extrauterine growth retardation: a multicentre randomised study in China
Authors: Yu M.‐X. , Zhuang S.‐Q. , Gao X.‐Y. , Tong X.‐M. , Yue S.‐J. , Shi L.‐P. , Chen D.‐M. , Liang K.
Published: January 2020

Background

Post‐discharge optimal growth and nutritional intake have beneficial effects for neurodevelopment in preterm very low birth weight infants (VLBWIs) with extrauterine growth retardation (EUGR). The present study aimed to compare the effects of a nutrient‐dense formula (NDF) to a post‐discharge formula (PDF) on post‐discharge growth of preterm VLBWIs with EUGR.

Methods

Forty‐eight preterm VLBWIs with EUGR at discharge were randomised to receive NDF (100 kcal per 100 mL; 2.6 g protein per 100 mL) or PDF (74 kcal per 100 mL; 1.95 g protein per 100 mL) for 1–6 months until body weight reached the 50th percentile on growth charts with corrected age. Volume, nutrient intake, anthropometry and biochemistry data were collected.

Results

Volume intake was lower in the NDF group than the PDF group during the first 2 months of feeding (P = 0.039 and 0.018, respectively).There were no significant differences in volume intake during months 2–6 of feeding. Energy, protein, carbohydrate and fat intake were higher in the NDF group during months 1–6 of feeding. There were no significant differences in weight, length, and head circumference Z‐scores during months 1–6 between the two groups. The △length Z‐score from discharge to month 6 was significantly higher in the NDF group than the PDF group (P = 0.043). No differences existed between the two groups with respect to biochemistry.

Conclusions

After discharge, preterm VLBWIs with EUGR fed a NDF gain anthropometric parameter Z‐scores similar to those for a PDF within 6 months of follow‐up. A NDF leading to gain in length requires further follow‐up.
Uncertainty, Incentives, and Misallocation
Authors: BAEK SEUNGJUN
Published: January 2020

This paper identifies a new propagation mechanism by which the effects of business cycle shocks amplify in the context of the dynamic stochastic general equilibrium framework. Business cycle shocks, such as heightened uncertainty, and positive monetary shocks endogenously magnify the cross‐sectional dispersion in idiosyncratic productivity. This induces entrepreneurs, who have asset substitution incentive, to distort the quality of an investment project, which amplifies the response of investment and output. Moreover, lenders reallocate credit from firms with a high marginal product of capital, in which the asset substitution problem is more prevalent, to firms with a low marginal product of capital, which in turn further depresses aggregate economic activities. A policy that subsidizes lenders to firms with a high marginal product during a recession improves the allocation of loans. Empirical evidence from the NBER‐CES Manufacturing Industry Database provides support for the model's predictions.
The biochemical basis of interactions between Glucocerebrosidase and alpha‐synuclein in GBA1 mutation carriers
Authors: Toffoli Marco , Smith Laura , Schapira Anthony H. V.
Published: January 2020

The discovery of genes involved in familial as well as sporadic forms of Parkinson disease (PD) constitutes an important milestone in understanding this disorder's pathophysiology and potential treatment. Among these genes, GBA1 is one of the most common and well‐studied, but it is still unclear how mutations in GBA1 translate into an increased risk for developing PD. In this review, we provide an overview of the biochemical and structural relationship between GBA1 and PD to help understand the recent advances in the development of PD therapies intended to target this pathway.

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Gene variability in matrix metalloproteinases in patients with recurrent aphthous stomatitis
Authors: Slezakova Simona , Borilova Linhartova Petra , Bartova Jirina , Petanova Jitka , Kuklinek Pavel , Fassmann Antonin , Dusek Ladislav , Izakovicova Holla Lydie
Published: January 2020

Background

The development of recurrent aphthous stomatitis (RAS), inflammatory disease of oral mucosa, is influenced by both environmental and genetic factors. The aim of this study was to investigate polymorphisms located in seven genes coding different types of matrix metalloproteinases (MMPs)—collagenases (MMP1, MMP8, and MMP13), gelatinases (MMP2 and MMP9), stromelysin (MMP3), and membrane‐type metalloproteinase (MMP16) in patients with RAS and healthy controls.

Methods

Totally, 223 subjects were included in this case‐control study and their detailed anamnestic, clinical, and laboratory parameters were recorded. Seventy‐seven patients with RAS and 146 controls were genotyped for seventeen polymorphisms in the MMPs genes using the real‐time polymerase chain reaction (PCR) or PCR with restriction analysis.

Results

Allele, genotype, and haplotype frequencies of the studied polymorphisms between RAS patients and controls were similar, except for allele distributions of MMP1 rs1144393, MMP9 rs3918242, and MMP16 rs10429371, which were different between patients with RAS and healthy controls (P = .023, P = .049 and P = .025, all Pcorr > 0.05, respectively). Moreover, the comparison of genotype frequencies (TT vs CC + CT) of the MMP16 rs10429371 variant showed a marginally significant difference between RAS patients and controls (P = .05, Pcorr > 0.05, OR = 1.68, 95% CI = 0.95‐2.98).

Conclusions

No significant relationship between investigated polymorphisms in seven MMPs genes and RAS development in the Czech population was observed in this study.
The Relationship between Active Labor Market Programs and Employability of the Long‐Term Unemployed
Authors: Nielsen Arendt Jacob , Lindegaard Andersen Henrik , Saaby Morten
Published: January 2020

It can be difficult to document whether active labor market programs are effective for the long‐term unemployed because their transitions to employment are rare. This study examines whether eight measures of employability are useful intermediate outcome measures for the long‐term unemployed. We use a repeated survey linked to administrative register data and estimate three‐way fixed‐effect models. The results show that self‐reported health is a useful outcome measure for the given population of long‐term unemployed in the following sense: Only this measure both predicts subsequent employment and is positively associated with prior participation in an active labor market program compared with non‐participation.
Comparison of three therapeutic regimens for genotype‐3 hepatitis C virus infection in a large real‐life multicentre cohort
Authors: Soria Alessandro , Fava Marco , Bernasconi Davide P. , Lapadula Giuseppe , Colella Elisa , Valsecchi Maria G. , Migliorino Guglielmo M. , D'Ambrosio Roberta , Landonio Simona , Schiavini Monica , Spinetti Angiola , Carriero Canio , Degasperi Elisabetta , Cologni Giuliana , Gatti Federico , Viganò Paolo , Hasson Hamid , Uberti‐Foppa Caterina , Pasulo Luisa , Baiguera Chiara , Rossotti Roberto , Vinci Maria , Puoti Massimo , Giorgini Alessia , Menzaghi Barbara , Lombardi Andrea , Pan Angelo , Aghemo Alessio , Grossi Paolo A. , Boldizzoni Roberto , Colombo Silvia , Viganò Mauro , Rumi Maria G. , Del Poggio Paolo , Valenti Luca , Giglio Omar , De Bona Anna , d'Arminio Monforte Antonella , Colombo Alberto , Spinelli Ombretta , Pigozzi Marie G. , Molteni Chiara , Bonfanti Paolo , Terreni Natalia , Perini Paolo , Capretti Andrea , Bella Daniele , Liani Cecilia , Polo Silvia , Aimo Gianpiero , Pagnucco Layla , Bhoori Sherrie , Centenaro Riccardo , Graffeo Massimo , Ciaccio Antonio , Dionigi Elena , Lazzaroni Sergio , Carderi Isabella , Di Marco Mariella , Rizzardini Giuliano , Noventa Franco , Lampertico Pietro , Fagiuoli Stefano
Published: January 2020

Background & Aims

In the direct‐acting antiviral era, treatment of genotype‐3 HCV (HCV‐GT3) is still challenging. Real‐life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir (DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap.

Methods

Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV‐GT3 patients consecutively treated within the Lombardia web‐based Navigatore HCV‐Network; differences in SVR12 across regimens were evaluated by logistic regression.

Results

Of the 2082 subjects with HCV‐GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV‐positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV‐RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P = .065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P = .007) and lower median pretreatment Log10HCV‐RNA (5.87 vs 6.20, P = .001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV‐RNA were independently associated with SVR12.

Conclusions

In a large real‐life setting of HCV‐GT3‐infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier‐to‐treat patients allows ribavirin‐free and shorter schedules without mining SVR12 in this <> genotype.
Meeting the Evil God Challenge
Authors: Page Ben , Baker‐Hytch Max
Published: January 2020

The evil God challenge is an argumentative strategy that has been pursued by a number of philosophers in recent years. It is apt to be understood as a parody argument: a wholly evil, omnipotent and omniscient God is absurd, as both theists and atheists will agree. But according to the challenge, belief in evil God is about as reasonable as belief in a wholly good, omnipotent and omniscient God; the two hypotheses are roughly epistemically symmetrical. Given this symmetry, thesis belief in an evil God and belief in a good God are taken to be similarly preposterous. In this paper, we argue that the challenge can be met, suggesting why the three symmetries that need to hold between evil God and good God – intrinsic, natural theology and theodicy symmetries – can all be broken. As such, we take it that the evil God challenge can be met.