bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatigue behaviour of a multiphase medium carbon steel: Comparison between ferrite/pearlite and tempered microstructures
Authors: Zhang Yating , Hu Zheng , Susmel Luca , Zhang Jing , Zhang Kun , Li Yansen , Wang Yang , Wei Bingchen
Published: June 2020

Fatigue crack growth is the essential process in the total life of components and is unavoidable in most structures and machines. In this study, the effects of cementite particles on the fatigue properties of medium carbon steel were investigated. A quenching and tempering treatment was developed to obtain uniformly distributed cementite particles with dozens of nanometres. To evaluate the fatigue properties, fatigue strength, fatigue crack growth rate and dynamic mechanical behaviour were examined. It was found that the fatigue strength of the tempered steel is much higher than that of air cooling ferrite/pearlite steel because the cementite particles act as barriers and hinder crack propagation during cyclic loading. More importantly, the high sensitivity of the damping peak to prior fatigue may play an important role on the fatigue history of multiphase medium carbon steel.
Clock gene polygenic risk score and seasonality in major depressive disorder and bipolar disorder
Authors: Ferrer Alex , Costas Javier , Gratacos Mònica , Martínez‐Amorós Èrika , Labad Javier , Soriano‐Mas Carles , Palao Diego , Menchón Jose Manuel , Crespo Jose Manuel , Urretavizcaya Mikel , Soria Virginia
Published: June 2020

Seasonal changes in mood and diurnal preference are two well‐characterized chronobiological phenotypes in major depressive disorder (MDD) and bipolar disorder (BD). The biological mechanisms regulating physiological changes related to seasonality and chronotype involve several genes known as “clock” or circadian genes. Our goal was to study the relationship between the polygenic risk score (PRS) obtained from a set of clock genes and chronobiological traits in patients with mood disorders. The sample included 445 patients with mood disorders (256 MDD; 189 BD). Seasonality was assessed using the Seasonal Pattern Assessment Questionnaire (SPAQ), and chronotype was assessed using the Horne and Östberg Morningness–Eveningness Questionnaire. We selected 248 single nucleotide polymorphisms located within 19 genes. PRS for both MDD and BD was calculated using the Psychiatric Genetics Consortium latest datasets as discovery samples. Another PRS was calculated using results from a genome‐wide association study focusing on chronotype. SPAQ results were significantly associated with MDD‐PRS (p = 0.037) and chronotype‐PRS (p = 0.019), which also showed a significant interaction with age (p = 0.039). No significant association was observed between the measured PRS and chronotype. Our results reflect that small effect variants associated with MDD and chronotype within clock genes are associated with seasonality traits in patients with mood disorders, further explaining the mechanism through which the circadian system might influence mood disorder clinical presentation. Future studies measuring PRS from specific gene sets and focusing on biological endophenotypes will help to elucidate the pathways from genetic variations to clinical outcome.
Methane emissions reduce the radiative cooling effect of a subtropical estuarine mangrove wetland by half
Authors: Liu Jiangong , Zhou Yulun , Valach Alex , Shortt Robert , Kasak Kuno , Rey‐Sanchez Camilo , Hemes Kyle S. , Baldocchi Dennis , Lai Derrick Y. F.
Published: June 2020

The role of coastal mangrove wetlands in sequestering atmospheric carbon dioxide (CO2) and mitigating climate change has received increasing attention in recent years. While recent studies have shown that methane (CH4) emissions can potentially offset the carbon burial rates in low‐salinity coastal wetlands, there is hitherto a paucity of direct and year‐round measurements of ecosystem‐scale CH4 flux (FCH4) from mangrove ecosystems. In this study, we examined the temporal variations and biophysical drivers of ecosystem‐scale FCH4 in a subtropical estuarine mangrove wetland based on 3 years of eddy covariance measurements. Our results showed that daily mangrove FCH4 reached a peak of over 0.1 g CH4‐C m−2 day−1 during the summertime owing to a combination of high temperature and low salinity, while the wintertime FCH4 was negligible. In this mangrove, the mean annual CH4 emission was 11.7 ± 0.4 g CH4‐C m–2 year−1 while the annual net ecosystem CO2 exchange ranged between −891 and −690 g CO2‐C m−2 year−1, indicating a net cooling effect on climate over decadal to centurial timescales. Meanwhile, we showed that mangrove FCH4 could offset the negative radiative forcing caused by CO2 uptake by 52% and 24% over a time horizon of 20 and 100 years, respectively, based on the corresponding sustained‐flux global warming potentials. Moreover, we found that 87% and 69% of the total variance of daily FCH4 could be explained by the random forest machine learning algorithm and traditional linear regression model, respectively, with soil temperature and salinity being the most dominant controls. This study was the first of its kind to characterize ecosystem‐scale FCH4 in a mangrove wetland with long‐term eddy covariance measurements. Our findings implied that future environmental changes such as climate warming and increasing river discharge might increase CH4 emissions and hence reduce the net radiative cooling effect of estuarine mangrove forests.
Immune microenvironment of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma: Relationship with histopathological and molecular classifications
Authors: Kurebayashi Yutaka , Kubota Naoto , Sakamoto Michiie
Published: June 2020

Tumor tissue is composed of tumor cells and tumor stroma. Tumor stroma contains various immune cells and non‐immune stromal cells, forming a complex tumor microenvironment which plays pivotal roles in regulating tumor growth. Recent successes in immunotherapies against tumors, including immune checkpoint inhibitors, have further raised interests in the immune microenvironment of liver carcinoma. The immune microenvironment of tumors is formed because of interactions among tumor cells, immune cells and non‐immune stromal cells, including fibroblasts and endothelial cells. Different patterns of immune microenvironment are observed among different tumor subtypes, and their clinicopathological significance and intertumor/intratumor heterogeneity are being intensively studied. Here, we review the immune microenvironment of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma, focusing on its histopathological appearance, clinicopathological significance, and relationship with histological and molecular classifications. Understanding the comprehensive histopathological picture of a tumor immune microenvironment, in addition to molecular and genetic approaches, will further potentiate the effort for precision medicine in the era of tumor‐targeting immunotherapy.
Relationship between apical periodontitis and atherosclerosis in rats: lipid profile and histological study
Authors: Conti L. C. , Segura‐Egea J. J. , Cardoso C. B. M. , Benetti F. , Azuma M. M. , Oliveira P. H. C. , Bomfim S. R. M. , Cintra L. T. A.
Published: June 2020

Aim

To investigate the relationship between apical periodontitis and atherosclerosis in rats by lipid profile and carotid artery intima tunic measurement, and histological and histometric evaluation of periapical lesions.

Methodology

Forty male Wistar rats were allocated into four groups: control (C), with apical periodontitis (AP), with atherosclerosis (AT) and with AP and AT (AP + AT). Atherosclerosis was induced using a high‐lipid diet associated with a surgical ligature in the carotid artery and a super dosage of vitamin D3. AP was induced via pulp exposure to the oral environment. At 45 and 75 days, serum levels of total cholesterol (TC), triglycerides (TG), high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol (LDL‐C) were measured. The maxillary and mandibular jaws and carotid artery were collected and processed for histological analysis. The Kruskal–Wallis or Mann–Whitney test was performed for nonparametric data, and the Tukey’s or Student’s t‐test was performed for parametric data (P < 0.05).

Results

In nonatherosclerotic animals, the induction of apical periodontitis increased TG levels significantly, from 63.1 ± 11.4 mg dL−1 in group C to 88.2 ± 7.9 mg dL−1 in the AP group (P < 0.05). The induction of AP was associated with a trend for higher TC and LDL‐C levels in atherosclerotic animals (P > 0.05); however, it only significantly increased TG levels, from 93.2 ± 18.0 mg dL−1 in AT group to 121.9 ± 14.5 mg dL−1 in the AP + AT group (P < 0.05). Animals in the AP + AT group had a 36.5% increase in the thickness of the carotid intima tunic when compared with the AT group (P < 0.05). The intensity of the inflammatory infiltrate was significantly larger in the AP + AT group when compared with AP group (P < 0.05). The AP + AT group exhibited significantly greater alveolar bone loss, with a periapical lesion size of 206.4 ± 56.3 × 104 μm2, compared with 151.4 ± 49.1 × 104 μm2 in the AP group (P < 0.05).

Conclusion

Apical periodontitis influenced triglyceride levels, increasing them even in the absence of atherosclerosis, and influenced the increase in the thickness of the carotid artery intima tunic in the presence of atherosclerosis. Atherosclerosis intensified the inflammatory reaction and increased bone resorption in periapical lesions.
Improving performance of recently introduced flow cytometry‐based approach of malignant cell screening in serous cavity effusion
Authors: Sun Jingfang , Ding Shuang , Zhu Liqiang , Liu Yun , Jiang Qingqing , Song Shuang , Chen Weimin , Li Shibao , Ma Ping
Published: June 2020

Introduction

Microscopy has been recognized as the “gold‐standard” cellular analysis of serous cavity effusion. However, this method is time‐consuming, labor‐intensive, and requires accomplished skills. Here, we investigated the efficiency of hematology analyzer in screening malignant cells in serous cavity effusion.

Methods

A total of 991 serous cavity effusion samples and 370 validation specimens collected from different departments were sent to the clinical laboratory for routine cell count using the automated hematology body fluid (BF) mode and exfoliative cytology simultaneously. High‐fluorescent cells (HFCs) were measured as the relative count (HF%) and absolute count (HF#) by BF mode. Receiver operating characteristic curve analysis was combined with scattergram rules to screen malignant cells.

Results

HF# and HF% in malignant samples (subgroup) were significantly higher than those in benign samples, and the HF# and HF% levels were different between ascites and pleural effusion (PE). The area under the curve values were also different between ascites and PE. Positive of malignant cells was very high when the ascites or PE sample touching Rule 1 positive and either Rule 2 negative or positive. The cutoff levels of HF# were 5.5 HFC/μL on the basis of Rules 1 and 2 negative, whereas 83.5 HFC/μL on the basis of Rule 1 negative but Rule 2 positive in ascites. By contrast, the cutoff levels of HF% were 0.55 HFC/100 WBC on the basis of Rules 1 and 2 negative, whereas 4.95 HFC/100 WBC on the basis of Rule 1 negative but Rule 2 positive in PE.

Conclusions

Serous cavity effusion will be increasingly analyzed using the automated hematology analyzer BF mode in the future because of its rapidness and convenience. The combined application of HFC with scattergram rules is a feasible and useful approach to screen malignant cells in serous cavity effusion.
Combined analysis of circRNA and mRNA profiles and interactions in patients with Diabetic Foot and Diabetes Mellitus
Authors: Zhao Wanni , Liang Jianfeng , Chen Zuoguan , Diao Yongpeng , Miao Gang
Published: June 2020

In order to elucidate the pathogenesis and explore new biomarkers for diabetes and diabetic foot (DF), an analysis using RNA sequencing affords broader insights into gene expression regulatory networks in DF. To better explore the molecular basis of DF, we carried out an analysis of circular RNA (circRNA) and messenger RNA (mRNA) expression profiles of serum samples from DF patients and diabetes mellitus (DM) patients. The potential roles and interactions of differentially expressed circRNAs and mRNAs were classified by gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Compared with diabetes patients, 279 mRNAs were upregulated and 353 mRNAs were downregulated in the serum of DF patients, and 33 circRNAs were differently expressed. The differential genes at the nodes of the interaction network were screened, and TLR6 RUNX1 and ST2 were found to be related to the progression of diabetes and DF. The enrichment pathway analysis revealed that the lysosomal pathway played a critical role in the occurrence and development of DF. TLR6, RUNX1, and ST2 mRNA expressions and the lysosomal pathway may be involved in the pathogenesis of diabetes and DF. In addition, methane metabolism and Chagas disease pathways were observed in the occurrence and development of DF, which is a new discovery in this study. This study provides clues on the molecular mechanisms of DF at the circRNA and mRNA levels.
Sufficiency, Priority, and Selecting Refugees
Authors: Gerver Mollie
Published: June 2020

There are more refugees than many states have a duty to accept. As a result, many states are permitted to accept only some refugees and not others. This raises the question of how states should select these refugees. I defend the claim that states should resettle the worst‐off refugees, and maximize the number of refugees gaining a sufficiently decent life. When resettling the worst off conflicts with maximising the number gaining a sufficiently decent life, states should select refugees to maximise aggregate benefits, with benefits holding greater weight the further refugees are from a sufficiency threshold. The only exception to this rule is when it entails wrongful discrimination, in which case states should only follow this rule if victims of discrimination benefit and consent to its implementation.
Parenting girls with Rett syndrome: An investigation on self‐perceived levels of stress
Authors: Pari Elisa , Cozzi Francesca , Rodocanachi Roidi Marina Luisa , Grange Francesca , Toshimori Kumiko , Ripamonti Enrico
Published: June 2020

Background

Although lives of parents of girls with Rett syndrome (RTT) are centred on the process of care, in the current literature their perceived levels of stress have been rarely investigated.

Methods

We analysed levels of stress in a sample of 79 fathers and mothers parenting girls with RTT, who were required to compile the Parenting Stress Index (PSI) questionnaire.

Results

We found clinical levels of stress in about 39% of fathers, as compared with 44% of the mothers. Severity of RTT, but not other factors such as the genetic domain, presence of epilepsy or scoliosis, predicted Total Stress scores in both fathers’ subsample and mothers’ subsample. A cumulative effect of caring, that is association of higher levels of stress with longer process of care, did also emerge from estimation of smoothing splines.

Conclusions

Fathers’ resources should be taken more into account, especially in the rehabilitation and socialization process of adults with RTT.
The utility of drug challenge testing in Brugada syndrome: A systematic review and meta‐analysis
Authors: Rattanawong Pattara , Kewcharoen Jakrin , Kanitsoraphan Chanavuth , Vutthikraivit Wasawat , Putthapiban Prapaipan , Prasitlumkum Narut , Mekraksakit Poemlarp , Mekritthikrai Raktham , Chung Eugene H.
Published: June 2020

Introduction

Brugada syndrome (BrS) is associated with ventricular arrhythmia leading to sudden cardiac death. Risk stratification is challenging, as major arrhythmic events (MAEs) are rare. We assessed the utility of drug challenge testing in BrS by a systematic review and meta‐analysis.

Methods and Results

We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2019. Included studies compared the incidence of MAE between spontaneous and drug challenge–induced Type 1. Mixed‐effects Poisson regression was used to calculate the incidence rate ratio (IRR). Eighteen studies from 2006 to 2018 were included (4099 patients, mean follow‐up: 4.5 years). Pooled annual incidences of MAE in spontaneous, drug challenge induced (regardless of symptoms), asymptomatic drug challenge induced, and symptomatic drug challenge–induced Type 1 were 23.8 (95% confidence interval [CI]: 19.8–27.8), 6.5 (95% CI: 3.9–9.1), 2.1 (95% CI: −0.3 to 4.4), and 19.6 (95% CI: 9.9–29.3) per 1000 person‐years, respectively. The incidence of MAE between symptomatic drug challenge induced and asymptomatic spontaneous Type 1 was not statistically different (IRR = 1.0; 95% CI: 0.6–1.7).

Conclusions

The incidence of MAE in drug challenge–induced Type 1 in asymptomatic patients is low. The incidence of MAE between symptomatic drug challenge induced and asymptomatic spontaneous Type 1 was similar.
A combined CaMKII inhibition and mineralocorticoid receptor antagonism via eplerenone inhibits functional deterioration in chronic pressure overloaded mice
Authors: Driessen Helen E. , Fontes Magda S. , van Stuijvenberg Leonie , Brans Maike A. , Goumans Marie‐Jose , Vos Marc A. , van Veen Toon A.
Published: June 2020

In the diseased and remodelled heart, increased activity and expression of Ca2+/calmodulin‐dependent protein kinase II (CaMKII), an excess of fibrosis, and a decreased electrical coupling and cellular excitability leads to disturbed calcium homeostasis and tissue integrity. This subsequently leads to increased arrhythmia vulnerability and contractile dysfunction. Here, we investigated the combination of CaMKII inhibition (using genetically modified mice expressing the autocamtide‐3‐related‐peptide (AC3I)) together with eplerenone treatment (AC3I‐Epler) to prevent electrophysiological remodelling, fibrosis and subsequent functional deterioration in a mouse model of chronic pressure overload. We compared AC3I‐Epler mice with mice only subjected to mineralocorticoid receptor (MR) antagonism (WT‐Epler) and mice with only CaMKII inhibition (AC3I‐No). Our data show that a combined CaMKII inhibition together with MR antagonism mitigates contractile deterioration as was manifested by a preservation of ejection fraction, fractional shortening, global longitudinal strain, peak strain and contractile synchronicity. Furthermore, patchy fibrosis formation was reduced, potentially via inhibition of pro‐fibrotic TGF‐β/SMAD3 signalling, which related to a better global contractile performance and a slightly depressed incidence of arrhythmias. Furthermore, the level of patchy fibrosis appeared significantly correlated to eplerenone dose. The addition of eplerenone to CaMKII inhibition potentiates the effects of CaMKII inhibition on pro‐fibrotic pathways. As a result of the applied strategy, limiting patchy fibrosis adheres to a higher synchronicity of contraction and an overall better contractile performance which fits with a tempered arrhythmogenesis.
Reproductive senescence and parental effects in an indeterminate grower
Authors: Depeux Charlotte , Lemaître Jean‐François , Moreau Jérôme , Dechaume‐Moncharmont François‐Xavier , Laverre Tiffany , Pauhlac Hélène , Gaillard Jean‐Michel , Beltran‐Bech Sophie
Published: June 2020

Reproductive senescence is the decrease of reproductive performance with increasing age and can potentially include trans‐generational effects as the offspring produced by old parents might have a lower fitness than those produced by young parents. This negative effect may be caused either by the age of the father, mother or the interaction between the ages of both parents. Using the common woodlouse Armadillidium vulgare, an indeterminate grower, as a biological model, we tested for the existence of a deleterious effect of parental age on fitness components. Contrary to previous findings reported from vertebrate studies, old parents produced both a higher number and larger offspring than young parents. However, their offspring had lower fitness components (by surviving less, producing a smaller number of clutches or not reproducing at all) than offspring born to young parents. Our findings strongly support the existence of trans‐generational senescence in woodlice and contradict the belief that old individuals in indeterminate growers contribute the most to recruitment and correspond thereby to the key life stage for population dynamics. Our work also provides rare evidence that the trans‐generational effect of senescence can be stronger than direct reproductive senescence in indeterminate growers.
Developing an impact library for forecasting surface water flood risk
Authors: Aldridge Timothy , Gunawan Oliver , Moore Robert J. , Cole Steven J. , Boyce Graeme , Cowling Rob
Published: June 2020

During surface water flooding events, emergency responders require detailed information on the risks posed in order to provide an appropriate and effective response. Few early warning systems quantitatively estimate the risk and impacts of surface water flooding. Improvements in computational processing capability, availability of new datasets and developments in forecasting models means that the forecasting information currently being supplied by the Flood Forecasting Centre can be improved upon through the application of a timely, impact‐based model. This article presents a novel approach to collating receptor datasets into a pre‐calculated Impact Library for use in a Hazard Impact Model (HIM) that will operate using real‐time probabilistic rainfall and surface runoff forecasts for England and Wales. The HIM provides an approach suitable for modelling flood impacts. Initial results are presented for a case study covering the 2012 floods in the North East of England. Information generated by the HIM provides additional benefits beyond current methods. Features include operator access to 1 km 15 min spatial–temporal data, analysis of individual impact criteria and modular refinement of the Impact Library to suit different situations. The HIM has been developed in partnership via the Natural Hazards Partnership.
Global epidemiology of lean non‐alcoholic fatty liver disease: A systematic review and meta‐analysis
Authors: Lu Feng‐Bin , Zheng Kenneth I , Rios Rafael S , Targher Giovanni , Byrne Christopher D , Zheng Ming‐Hua
Published: June 2020

Background and Aim

Lean non‐alcoholic fatty liver disease (NAFLD) is a potentially metabolically unhealthy state that refers to NAFLD occurring in non‐overweight/nonobese subjects. Yet its global epidemiology and metabolic characteristics are not extensively elucidated.

Methods

PubMed, EMBASE, Web of Science and Cochrane databases were searched for eligible studies until January 2020. Random‐effects/fixed‐effects models were used to estimate the global prevalence of lean NAFLD and to compare clinical characteristics among lean non‐NAFLD, lean NAFLD, and overweight/obese NAFLD subjects. “Lean” NAFLD was defined by ethnic‐specific body mass index measurements in the normal range. Meta‐regression and subgroup analyses were performed to determine potential sources of heterogeneity.

Results

A total of 33 observational studies were included with 205 307 individuals from 14 countries. The global prevalence of lean NAFLD was 4.1% (95% confidence interval [CI]: 3.4–4.8%). In lean subjects, the prevalence of NAFLD was 9.7% (95% CI: 7.7–11.8%). The prevalence of lean NAFLD with diabetes, hypertension, metabolic syndrome, dyslipidemia, or central obesity was 0.6% (95% CI: 0.4–0.9%), 1.8% (95% CI: 1.2–2.5%), 1.4% (95% CI: 1.0–1.9%), 2.8% (95% CI: 1.9–3.7%), and 2.0% (95% CI: 1.6–2.4%), respectively. The prevalence of lean NAFLD showed an upward trend between 1988 and 2017. Asian individuals had the highest prevalence of lean NAFLD (4.8%, 95% CI: 4.0–5.6%). Middle‐aged people (45–59 years old) had the highest prevalence of lean NAFLD (4.4%, 95% CI: 3.2–5.5%). The prevalence of metabolic complications in lean non‐NAFLD, lean NAFLD, and overweight/obese NAFLD groups increased sequentially.

Conclusions

Lean NAFLD occurs with metabolic complications and is not an uncommon condition. The highest prevalence of lean NAFLD occurs in middle‐aged individuals of Asian countries.
Comparative anatomy of the mammalian neuromuscular junction
Authors: Boehm Ines , Alhindi Abrar , Leite Ana S. , Logie Chandra , Gibbs Alyssa , Murray Olivia , Farrukh Rizwan , Pirie Robert , Proudfoot Christopher , Clutton Richard , Wishart Thomas M. , Jones Ross A. , Gillingwater Thomas H.
Published: June 2020

The neuromuscular junction (NMJ)—a synapse formed between lower motor neuron and skeletal muscle fibre—represents a major focus of both basic neuroscience research and clinical neuroscience research. Although the NMJ is known to play an important role in many neurodegenerative conditions affecting humans, the vast majority of anatomical and physiological data concerning the NMJ come from lower mammalian (e.g. rodent) animal models. However, recent findings have demonstrated major differences between the cellular anatomy and molecular anatomy of human and rodent NMJs. Therefore, we undertook a comparative morphometric analysis of the NMJ across several larger mammalian species in order to generate baseline inter‐species anatomical reference data for the NMJ and to identify animal models that better represent the morphology of the human NMJ in vivo. Using a standardized morphometric platform (‘NMJ‐morph’), we analysed 5,385 individual NMJs from lower/pelvic limb muscles (EDL, soleus and peronei) of 6 mammalian species (mouse, cat, dog, sheep, pig and human). There was marked heterogeneity of NMJ morphology both within and between species, with no overall relationship found between NMJ morphology and muscle fibre diameter or body size. Mice had the largest NMJs on the smallest muscle fibres; cats had the smallest NMJs on the largest muscle fibres. Of all the species examined, the sheep NMJ had the most closely matched morphology to that found in humans. Taken together, we present a series of comprehensive baseline morphometric data for the mammalian NMJ and suggest that ovine models are likely to best represent the human NMJ in health and disease.
The edge out punch: An advancement that reduces transections in follicular unit excision hair transplantation
Authors: Trivellini Roberto , Gupta Aditya K.
Published: June 2020

Background

The follicular unit excision (FUE) technique has become the preferred method for hair transplants over the traditional strip harvest technique due to low scar visibility and shorter recovery time for the patient. However, a limitation of the FUE technique is the potential for graft trauma due to the small diameter, sharp punches used to harvest individual follicular units.

Aims

Here, we introduce the novel edge out FUE punch that is designed with a thicker wall and has an internal bevel. We describe how the dynamics of this punch reduces the risk of follicle transection.

Methods

A review of the available literature and information on the edge out punch in comparison with other punch shapes, as well as the authors' experience in this area, is provided.

Results

The edge out punch is designed with thick walls and an internal bevel, placing the sharp cutting edge on the outer diameter. The dynamics of this punch aid in directing the graft into the center of the punch lumen and keeps the sharp cutting edge away from the hair follicles deeper in the dermis, reducing the risk of follicle transection.

Conclusion

The dynamics of the forces generated by the edge out punch aid in minimizing follicular transections during graft harvesting. By understanding the dynamics behind this novel punch, hair restoration surgeons (HRSs) can optimize their surgical technique to obtain consistently high‐quality grafts during FUE.
Public perception of generic medicines in Malta
Authors: Sammut Bartolo Nicolette , Ignas Louella , Wirth Francesca , Attard Pizzuto Maresca , Vella Szijj Janis , Camilleri Liberato , Serracino-Inglott Anthony , Azzopardi Lilian M
Published: June 2020

Objectives

To assess the perception of generic medicines among the general public in Malta.

Methods

A self-administered questionnaire was developed to assess knowledge, attitudes and use of generic medicines. The questionnaire was disseminated to a sample of the public recruited by convenience sampling in five localities in Malta. Descriptive statistics were undertaken.

Key findings

A total of 228 participants completed the questionnaire; 54% were female, 42% were ≥60 years old, and 37% had up to secondary education level. Sixty-one per cent of the participants were aware of the correct definition of a generic medicine, and 55% stated that they had previously used generic medicines. Twenty per cent of the participants had never used generic medicines since they perceived them to be inferior in quality or less effective compared to their originator counterparts. Fifty-four per cent of the participants would switch to a generic medicine if the originator product was out-of-stock and 38% would pay between 1% and 20% less for a generic medicine compared to the originator product.

Conclusions

Participants in this study exhibited a positive overall perception regarding generic medicines, demonstrating improvement in perception from a previous local study. The majority of participants were knowledgeable about generic medicines, had previously used generic medicines and would switch to a generic medicine if the originator product was not in stock.
Erich Przywara’s Late Reception of Luther
Authors: Morton Adam T.
Published: June 2020

Erich Przywara’s late career writings have to this point received little attention in English. While Przywara’s earlier writings include both significant dialogue with Protestant theologians (most prominently Karl Barth) and occasional references to Martin Luther, Luther takes on a new prominence in his work after the Second World War. This article seeks to describe Przywara’s late reception of Luther, including its historical circumstances and Przywara’s engagement with Luther scholarship, and to assess Przywara’s use and sharp criticism of Luther in his theology of exchange. Since exchange is positioned as the material theological center of the analogy of being, Przywara has drawn important concepts from Luther into the heart of his own theology. This article further argues that at a key point Przywara’s criticism of Luther fails, leaving his relation to Luther ambiguous. A concluding attempt is made to show both the overlooked ecumenical potential of Przywara’s engagement with Luther, and to illuminate the fundamental fissure that still separates their theologies.
Infection cushions of Fusarium graminearum are fungal arsenals for wheat infection
Authors: Mentges Michael , Glasenapp Anika , Boenisch Marike , Malz Sascha , Henrissat Bernard , Frandsen Rasmus J.N. , Güldener Ulrich , Münsterkötter Martin , Bormann Jörg , Lebrun Marc‐Henri , Schäfer Wilhelm , Martinez‐Rocha Ana Lilia
Published: June 2020

Fusarium graminearum is one of the most destructive plant pathogens worldwide, causing fusarium head blight (FHB) on cereals. F. graminearum colonizes wheat plant surfaces with specialized unbranched hyphae called runner hyphae (RH), which develop multicelled complex appressoria called infection cushions (IC). IC generate multiple penetration sites, allowing the fungus to enter the plant cuticle. Complex infection structures are typical for several economically important plant pathogens, yet with unknown molecular basis. In this study, RH and IC formed on the surface of wheat paleae were isolated by laser capture microdissection. RNA‐Seq‐based transcriptomic analyses were performed on RH and IC and compared to mycelium grown in complete medium (MY). Both RH and IC displayed a high number of infection up‐regulated genes (982), encoding, among others, carbohydrate‐active enzymes (CAZymes: 140), putative effectors (PE: 88), or secondary metabolism gene clusters (SMC: 12 of 67 clusters). RH specifically up‐regulated one SMC corresponding to aurofusarin biosynthesis, a broad activity antibiotic. IC specifically up‐regulated 248 genes encoding mostly putative virulence factors such as 7 SMC, including the mycotoxin deoxynivalenol and the newly identified fusaoctaxin A, 33 PE, and 42 CAZymes. Furthermore, we studied selected candidate virulence factors using cellular biology and reverse genetics. Hence, our results demonstrate that IC accumulate an arsenal of proven and putative virulence factors to facilitate the invasion of epidermal cells.
Live‐imaging of revertant and therapeutically restored dystrophin in the DmdEGFP‐mdx mouse model for Duchenne muscular dystrophy
Authors: Petkova M. V. , Stantzou A. , Morin A. , Petrova O. , Morales‐Gonzalez S. , Seifert F. , Bellec‐Dyevre J. , Manoliu T. , Goyenvalle A. , Garcia L. , Richard I. , Laplace‐Builhé C. , Schuelke M. , Amthor H.
Published: June 2020

Background

Dmdmdx, harbouring the c.2983C>T nonsense mutation in Dmd exon 23, is a mouse model for Duchenne muscular dystrophy (DMD), frequently used to test therapies aimed at dystrophin restoration. Current translational research is methodologically hampered by the lack of a reporter mouse model, which would allow direct visualization of dystrophin expression as well as longitudinal in vivo studies.

Methods

We generated a DmdEGFP‐mdx reporter allele carrying in cis the mdx‐23 mutation and a C‐terminal EGFP‐tag. This mouse model allows direct visualization of spontaneously and therapeutically restored dystrophin‐EGFP fusion protein either after natural fibre reversion, or for example, after splice modulation using tricyclo‐DNA to skip Dmd exon 23, or after gene editing using AAV‐encoded CRISPR/Cas9 for Dmd exon 23 excision.

Results

Intravital microscopy in anaesthetized mice allowed live‐imaging of sarcolemmal dystrophin‐EGFP fusion protein of revertant fibres as well as following therapeutic restoration. Dystrophin‐EGFP‐fluorescence persisted ex vivo, allowing live‐imaging of revertant and therapeutically restored dystrophin in isolated fibres ex vivo. Expression of the shorter dystrophin‐EGFP isoforms Dp71 in the brain, Dp260 in the retina, and Dp116 in the peripheral nerve remained unabated by the mdx‐23 mutation.

Conclusion

Intravital imaging of DmdEGFP‐mdx muscle permits novel experimental approaches such as the study of revertant and therapeutically restored dystrophin in vivo and ex vivo.
Gastrointestinal symptoms and cardiac vagal tone in type 1 diabetes correlates with gut transit times and motility index
Authors: Wegeberg Anne‐Marie L. , Brock Christina , Ejskjaer Niels , Karmisholt Jesper S. , Jakobsen Poul‐Erik , Drewes Asbjørn M. , Brock Birgitte , Farmer Adam D.
Published: June 2020

Background

Although gastrointestinal (GI) symptoms are common in diabetes, they frequently do not correlate with measurable sensorimotor abnormalities. The wireless motility capsule (WMC) measures pressure, temperature, and pH as it traverses the GI tract wherefrom transit times and motility indices are derived. The aim was to investigate whether GI symptoms correlate with changes in (a) segmental transit times, (b) segmental motility index, (c) cardiac vagal tone, or (d) presence/absence of peripheral neuropathy in type 1 diabetes.

Methods

Gastrointestinal symptoms in 104 participants with type 1 diabetes were measured using Gastroparesis Cardinal Symptoms Index and Gastrointestinal Symptom Rating Scale. All underwent standardized WMC investigation measuring segmental transit time and motility. Cardiac vagal tone and presence of peripheral neuropathy were measured using electrocardiographic and nerve conduction velocity testing.

Key Results

Colonic transit time was correlated with postprandial fullness (P = .01) and constipation (P = .03), while decreased colonic motility index was correlated with diarrhea (P = .01) and decreased bloating (P < .05). Symptoms were not correlated with gastric or small bowel transit time or motility index. In participants with low cardiac vagal tone, gastric motility index (P < .01) and colonic transit time (P < .05) were increased, but not in those with peripheral neuropathy. Abdominal pain was decreased with both peripheral neuropathy (P = .04) and decreased cardiac vagal tone (P = .02).

Conclusions and Inferences

This study supports the rationale for whole gut investigation, using not only transit times but incorporating contractility indices as well. Furthermore, a decreased parasympathetic modulation and an increased hyposensate state appear to be present in type 1 diabetes.
Bile reflux in patients with nerd is associated with more severe heartburn and lower values of mean nocturnal baseline impedance and chemical clearance
Authors: de Bortoli Nicola , Gyawali C. Prakash , Frazzoni Marzio , Tolone Salvatore , Frazzoni Leonardo , Vichi Eleonora , Visaggi Pierfrancesco , Bellini Massimo , Marabotto Elisa , Penagini Roberto , Savarino Vincenzo , Marchi Santino , Savarino Edoardo V.
Published: June 2020

Background

Mean nocturnal baseline impedance (MNBI) and postreflux swallow‐induced peristaltic wave (PSPW) index are novel impedance‐based markers of reflux, but the effect of bile reflux on these metrics is unknown. The aim of this study was to evaluate bile reflux, MNBI, and PSPW index in patients with endoscopy‐negative GERD partially responsive to PPI therapy.

Methods

All patients underwent off‐PPI endoscopy, esophageal manometry, multichannel intraluminal impedance pH (MII‐pH), and bile reflux monitoring. Abnormal esophageal acid exposure time (AET) was required for inclusion. Symptom intensity (using 10‐cm visual analog scales), and conventional and novel MII‐pH metrics were compared between patients with and without abnormal bile reflux.

Key Results

We evaluated 42 NERD patients (29 males, mean age: 53.4 ± 13. years), mean AET 6.1 ± 2%, of which 21 had abnormal bile reflux (Group A, 10.2 ± 4.9%), and 21 had normal bile reflux (Group B, 0.4 ± 0.1%, P < .05 compared with Group A). Heartburn reporting on PPI was higher in Group A (7.2 ± 2.1 vs 5.8 ± 0.9; P = .002), but AET, number of reflux events (acidic and weakly acidic), did not differ between the two groups. However, both PSPW index and MNBI were lower in Group A (P < .001). A strong inverse linear correlation was found between bile reflux and both MNBI (Pearson's test; R = −0.714; P < .001) and PSPW index (R = −0.722; P < .001).

Conclusions and Inferences

Compared to acid reflux alone, the presence of bile in an acidic esophageal environment is associated with more severe heartburn, lesser relief from PPI therapy, higher impairment of esophageal mucosal integrity and less effective chemical clearance.
Catheter ablation of atrial fibrillation in cardiac amyloidosis
Authors: Black‐Maier Eric , Rehorn Michael , Loungani Rahul , Friedman Daniel J. , Alenezi Fawaz , Geurink Kyle , Pokorney Sean D. , Daubert James P. , Sun Albert Y. , Atwater Brett D. , Jackson Kevin P. , Hegland Donald D. , Thomas Kevin L. , Bahnson Tristram D. , Khouri Michel G. , Piccini Jonathan P.
Published: June 2020

Background

Cardiac amyloidosis is a progressive infiltrative disease involving deposition of amyloid fibrils in the myocardium and cardiac conduction system that frequently manifests with heart failure (HF) and arrhythmias, most frequently atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT).

Methods

We performed an observational retrospective study of patients with a diagnosis of cardiac amyloid who underwent catheter ablation at our institution between January 1, 2011 and December 1, 2018. Patient demographics, procedural characteristics, and outcomes were determined by manual chart review.

Results

A total of 13 catheter ablations were performed over the study period in patients with cardiac amyloidosis, including 10 AT/AF/AFL ablations and three atrioventricular nodal ablations. Left ventricular ejection fraction was lower at the time of AV node ablation than catheter ablation of AT/AF/AFL (23% vs 40%, P = .003). Cardiac amyloid was diagnosed based on the results of preablation cardiac MRI results in the majority of patients (n = 7, 70%). The HV interval was prolonged at 60 ± 15 ms and did not differ significantly between AV nodal ablation patients and AT/AF/AFL ablation patients (69 ± 18 ms vs 57 ± 14 ms, P = .36). The majority of patients undergoing AT/AF/AFL ablation had persistent AF (n = 7, 70%) and NYHA class II (n = 5, 50%) or III (n = 5, 50%) HF symptoms, whereas patients undergoing AV node ablation were more likely to have class IV HF (n = 2, 66%, P = .014). Arrhythmia‐free survival in CA patients after catheter ablation of AT/AF/AFL was 40% at 1 year and 20% at 2 years.

Conclusions

Catheter ablation of AT/AF/AFL may be a feasible strategy for appropriately selected patients with early to mid‐stage CA, whereas AV node ablation may be more appropriate in patients with advanced‐stage CA.
Issues of infant feeding for postnatal prevention of human T‐cell leukemia/lymphoma virus type‐1 mother‐to‐child transmission
Authors: Itabashi Kazuo , Miyazawa Tokuo , Nerome Yasuhito , Sekizawa Akihiko , Moriuchi Hiroyuki , Saito Shigeru , Yonemoto Naohiro
Published: June 2020

Background

Nationwide antenatal human T‐cell leukemia/lymphoma virus type‐1 (HTLV‐1) antibody screening has been conducted in Japan. The purpose of our study was to clarify the issues related to feeding options to prevent postnatal mother‐to‐child transmission.

Methods

Of the pregnant carriers at 92 facilities in Japan between 2012 and 2015, 735 were followed prospectively. Among the children born to them, 313 (42.6%) children were followed up to the age of 3 and tested for HTLV‐1 antibodies. The mother‐to‐child transmission rate was calculated for each feeding option selected before birth.

Results

Among the 313 pregnant carriers, 55.0, 35.1, 6.1, and 3.8% selected short‐term breast‐feeding (≤3 months), exclusive formula feeding, frozen‐thawed breast‐milk feeding, and longer‐term breast‐feeding, respectively. Despite short‐term breast‐feeding, 8–18% of the mothers continued breast‐feeding for 4–6 months. The mother‐to‐child transmission rate with short‐term breast‐feeding was 2.3% (4/172), and its risk ratio compared with that of exclusive formula feeding was not significantly different (0.365; 95% CI: 0.116–1.145). Because of the small number of children who were fed by frozen‐thawed breast‐milk, their mother‐to‐child transmission rate was not statistically reliable.

Conclusions

Pregnant HTLV‐1 carriers tended to select short‐term breast‐feeding in Japan. While short‐term breast‐feeding was not always easy to wean within 3 months, it may be a viable option for preventing postnatal mother‐to‐child transmission because the vertical transmission rate with short‐term breast‐feeding was not significantly higher than that with exclusive formula feeding. Increasing the follow‐up rates for children born to pregnant carriers may provide clearer evidence of preventative effects by short‐term breast‐feeding and frozen‐thawed breast‐milk feeding.
Evaluation of respiratory center function in congenital central hypoventilation syndrome by monitoring electrical activity of the diaphragm
Authors: Yamada Yosuke , Hasegawa Hisaya , Henmi Nobuhide , Tsuruta Shio , Wasa Masanori , Kihara Hirotaka , Kodera Takayuki , Kouyama Toshinari , Kumazawa Kensuke
Published: June 2020

Background

A definitive diagnosis of congenital central hypoventilation syndrome (CCHS) is made by genetic testing. However, there are only a few examinations that warrant genetic testing. Electrical activity of the diaphragm (Edi) reflects neural respiratory drive from respiratory center to diaphragm. We evaluated the function of the respiratory center in CCHS by Edi monitoring.

Methods

Monitoring of Edi was performed in six CCHS cases without mechanical ventilation. The monitoring time was 30 consecutive minutes from wakefulness to sleep. The TcPCO2 or EtCO2 and SpO2 were recorded simultaneously.

Results

The Edi peak during wakefulness was 14.0 (10.3–21.0) µV and the Edi peak during sleep was 6.7 (3.8–8.0) µV. The Edi peak during sleep was significantly lower than the Edi peak during wakefulness, and patients were in a state of hypoventilation. Although TcPCO2 or EtCO2 increased due to hypoventilation, an increase in the Edi peak that reflects central respiratory drive was not observed. ΔEdi/ΔCO2 was −0.06μV/mmHg. Maximum EtCO2 or TcPco2 was 51 mmHg, and the average SpO2 was 91.5% during monitoring.

Conclusions

We confirmed that Edi monitoring could evaluate the function of the respiratory center and reproduce the hypoventilation of CCHS. The present study suggested that Edi monitoring is a useful examination in deciding whether to perform genetic testing or not and it may lead to an early diagnosis of CCHS.
High prevalence of latent tuberculosis in hematopoietic stem cell transplant recipients: A First Report
Authors: Mahmoudi Shima , Pourakbari Babak , Sadeghi Reihaneh Hosseinpour , Hamidieh Amir Ali , Safari Sharari Alieh , Salajegheh Pouria , Aziz‐Ahari Alireza , Mamishi Setareh
Published: June 2020

TB is an increasing health problem, and patients undergoing HSCT are more prone to develop tuberculosis. The aim of our study was to evaluate prevalence of latent tuberculosis in HSCT recipients. In this study, 84 patients (2 months to 18 years) who were candidates for HSCT at the referral hospital of Tehran Children's Medical Center were enrolled. The TST and the QFT‐GIT test were performed in all 84 patients, simultaneously. LTBI was considered when one of the tests was positive. Overall, the prevalence of LTBI in HSCT recipients in our study was 12% (10 cases). TST induration ≥5 mm was seen in only three patients (3.5%). Eight patients (9.5%) had a positive result for IGRA test, and 11 of them (13%) had indeterminate QFT‐GIT result. The agreement between the TST results (induration size ≥5 mm) and the QFT‐GIT results was poor (kappa = 0.14). In conclusion, there was a high rate of discordance between TST and IGRA results with many more positive QFT‐GIT tests. However, more studies are needed in this population to determine whether this discordance reflects true infection.
The Case against Commercial Antivirus Software: Risk Homeostasis and Information Problems in Cybersecurity
Authors: Jardine Eric
Published: June 2020

New cybersecurity technologies, such as commercial antivirus software (AV), sometimes fail to deliver on their promised benefits. This article develops and tests a revised version of risk homeostasis theory, which suggests that new cybersecurity technologies can sometimes have ill effects on security outcomes in the short run and little‐to‐no effect over the long run. It tests the preliminary plausibility of four predictions from the revised risk homeostasis theory using new survey data from 1,072 respondents. The estimations suggest the plausible operation of a number of risk homeostasis dynamics: (1) commercial AV users are significantly more likely to self‐report a cybersecurity event in the past year than nonusers, even after correcting for potential reverse causality and informational mechanisms; (2) nonusers become somewhat less likely to self‐report a cybersecurity event as the perceived riskiness of various e‐mail‐based behaviors increases, while commercial AV users do not; (3) the negative short‐run effect of commercial AV use on cybersecurity outcomes fade over time at a predicted rate of about 7.03 percentage points per year of use; and (4) after five years of use, commercial AV users are statistically indistinguishable from nonusers in terms of their probability of self‐reporting a cybersecurity event as perceptions of risky e‐mail‐based behaviors increase.