bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory Effect of Betanin From Hylocereus ocamponis Against Steatohepatitis in Mice Fed a High-Fat Diet
Authors: Lugo-Radillo Agustin , Delgado-Enciso Ivan , Rodriguez-Hernandez Alejandrina , Peña-Beltran Elpidio , Martinez-Martinez Rafael , Galvan-Salazar Hector
Published: July 2020

Betanin is a phytocompound whose effect in steatohepatitis has not yet been tested. Betanin was extracted from the fruits of Hylocereus ocamponis, and its effects were evaluated in a mice model for non-alcoholic fatty liver disease. Six-week-old male BALB/c mice fed with a high-fat diet received 9.6 mg of betanin per day during 40 days. Body, liver, and epididymal fat pad weights and the levels of blood serum total cholesterol, triglycerides, high-density lipoproteins, alanine aminotransferase, blood nitrogen urea, creatinine, and total antioxidant capacity were measured. Hepatosteatosis and inflammatory infiltration were categorized, and the relative cell area of hepatocytes was determined. Betanin inhibited the inflammatory infiltration of the liver ( P = 4.000 × 10−6) and the necrosis of hepatocytes ( P = 9.634 × 10−7); it also produced a predominance of microvesicular steatosis ( P = 9.634 × 10−7), decreased epididymal fat pad weight ( P = 8.250 × 10−4), and increased blood serum total cholesterol ( P = 0.011). Betanin is a promising compound for fatty liver, steatohepatitis, and chronic liver disease.
Protective Effect and Mechanism of Fruit Extract of Aegle marmelos Against Amyloid-β Toxicity in a Transgenic Caenorhabditis elegans
Authors: Keowkase Roongpetch , Kijmankongkul Nattanon , Sangtian Wanapong , Poomborplab Sireethorn , Santa-ardharnpreecha Chatpiti , Weerapreeyakul Natthida , Sitthithaworn Worapan
Published: July 2020

Alzheimer’s disease (AD) is the most common form of dementia found in the elderly. AD is caused by the accumulation of toxic proteins including amyloid-β (Aβ). The purpose of this study was to investigate the effect of fruit extract of Aegle marmelos against Aβ toxicity in Caenorhabditis elegans. The fruit of A. marmelos has been used in a traditional Thai herb formula in fatigue patients recovering from illnesses such as fever and diarrhea. We used a transgenic C. elegans strain CL4176, which expresses the human Aβ42, to investigate the effects and the mechanisms of action of the extracts against Aβ toxicity. The extract of A. marmelos significantly delayed Aβ-induced paralysis. Aegle marmelos lost the ability to delay Aβ-induced paralysis in worms fed with daf-16 ribonucleic acid interference (RNAi) bacteria, but not in worms fed with hsf-1 and skin-1 RNAi bacteria. These results indicated that daf-16 transcription factor was required for A. marmelos-mediated delayed paralysis. Aegle marmelos enhanced the level of daf-16 gene. Taken together, these results indicated that A. marmelos reduced Aβ toxicity via the DAF-16-mediated cell signaling pathway. In addition, A. marmelos reduced toxic Aβ oligomers. Aegle marmelos also displayed antioxidative effect in in vivo as it enhanced resistance to paraquat-induced oxidative stress in wild type worms. All of the results suggested that A. marmelos can protect against Aβ-induced toxicity and can be a potential candidate for the prevention or treatment of AD.
On the ethical dimension of irregular migrants’ lives: Affect, becoming and information
Authors: Tedeschi Miriam
Published: July 2020

This article operationalises Simondon’s theory of becoming and Deleuze and Spinoza’s ethics and unfolds their conceptualisations in the lives of a group of irregular migrants in Finland. From an ontological and ontogenetic perspective, individuals and their environment are always in a non-complete, non-linear and ethically affective state of becoming. In this sense, migrant bodies register the positive and negative affections accumulated over time, and, via information, make them a material, yet unfinished, and ready to be challenged again, part of their becoming. Applying these concepts to ethnographic fieldwork, this article highlights three dimensions of the observed irregular migrants’ becoming: their relentless efforts of becoming themselves through hardships; non-linear tensions with disparate realities, such as the bureaucratic procedures, and the negative affections the latter entail; and the struggle towards positive affections in temporary stabilities (e.g. in community life). In focusing on the processual and ontological making of migrants in their environment, the article contributes to broader debates regarding the non-linear and ethical dimensions of their everyday lives, as well as their capacity of transforming themselves, and aims at opening up dialogues on the significance of an ontogenetic approach to the field of irregular migration and beyond.
Safety and effectiveness of riociguat for chronic thromboembolic pulmonary hypertension in real‐world clinical practice: interim data from post‐marketing surveillance in Japan
Authors: Tanabe Nobuhiro , Ogo Takeshi , Hatano Masaru , Kigawa Ayaka , Sunaya Toshiyuki , Sato Shoichiro
Published: July 2020

This multicenter, prospective, non‐interventional study (ClinicalTrials.gov: NCT02117791) evaluated the safety and effectiveness of riociguat for chronic thromboembolic pulmonary hypertension in Japanese clinical practice, registering all patients with chronic thromboembolic pulmonary hypertension treated with riociguat following its launch in Japan in April 2014. Safety was assessed by analyzing the adverse drug reactions. Effectiveness measurements included the assessment of change in World Health Organization functional class, six‐minute walk test, and hemodynamics. Overall, 1031 patients were included in the safety analysis with 811 (78.7%) patients in World Health Organization functional class II/III. The mean treatment duration was 591.4 days (median 441.0 days). Adverse drug reactions were reported in 19.5% of patients, the most common being hypotension (5.9%), headache (3.0%), dizziness (1.9%), and gastroesophageal reflux disease (1.5%). Serious adverse drug reactions were reported in 2.1% of patients. Estimated survival was 97.0% at one year, 95.8% at two years, and 94.4% at three years. The effectiveness analysis (n = 1027) showed significant increases from baseline in six‐minute walking distance, and significant reductions from baseline in mean pulmonary arterial pressure and pulmonary vascular resistance. These interim results of riociguat in Japanese patients with chronic thromboembolic pulmonary hypertension demonstrated a safety profile that was generally consistent with those of pivotal clinical studies. The study is ongoing, and will continue to provide insights into the safety and effectiveness of riociguat in real‐world practice.
The effects of genetic deletion of Macrophage migration inhibitory factor on the chronically hypoxic pulmonary circulation
Authors: Li Lili , Xu Maojia , Rowan Simon C. , Howell Katherine , Russell‐Hallinan Adam , Donnelly Seamas C. , McLoughlin Paul , Baugh John A.
Published: July 2020

While it is well established that the haemodynamic cause of hypoxic pulmonary hypertension is increased pulmonary vascular resistance, the molecular pathogenesis of the increased resistance remains incompletely understood. Macrophage migration inhibitory factor is a pleiotropic cytokine with endogenous tautomerase enzymatic activity as well as both intracellular and extracellular signalling functions. In several diseases, macrophage migration inhibitory factor has pro‐inflammatory roles that are dependent upon signalling through the cell surface receptors CD74, CXCR2 and CXCR4. Macrophage migration inhibitory factor expression is increased in animal models of hypoxic pulmonary hypertension and macrophage migration inhibitory factor tautomerase inhibitors, which block some of the functions of macrophage migration inhibitory factor, and have been shown to attenuate hypoxic pulmonary hypertension in mice and monocrotaline‐induced pulmonary hypertension in rats. However, because of the multiple pathways through which it acts, the integrated actions of macrophage migration inhibitory factor during the development of hypoxic pulmonary hypertension were unclear. We report here that isolated lungs from adult macrophage migration inhibitory factor knockout (MIF–/–) mice maintained in normoxic conditions showed greater acute hypoxic vasoconstriction than the lungs of wild type mice (MIF+/+). Following exposure to hypoxia for three weeks, isolated lungs from MIF–/– mice had significantly higher pulmonary vascular resistance than those from MIF+/+ mice. The major mechanism underlying the greater increase in pulmonary vascular resistance in the hypoxic MIF–/– mice was reduction of the pulmonary vascular bed due to an impairment of the normal hypoxia‐induced expansion of the alveolar capillary network. Taken together, these results demonstrate that macrophage migration inhibitory factor plays a central role in the development of the pulmonary vascular responses to chronic alveolar hypoxia.
Radiofrequency denervation of the lumbar facet joints: guidelines for the RADICAL randomised controlled trial
Authors: Price Cathy , Reeves Barney , Ahmad Alia , Baloch Mohjir , Baranidharan Ganesan , Correa Robin , McCormick Tim , Sharma Manohar , Veemarajan Bala , Grimwood Margot , Pirie Katrina Ishbel , Wylde Vikki
Published: July 2020

Background and aim:

The RADICAL trial has been funded by the National Institute for Health Research (NIHR) to evaluate the clinical and cost-effectiveness of radiofrequency denervation (RFD) for low back pain. Recommendations have been published which aim to standardise selection of patients and RFD technique. However, it is important to ensure these recommendations are acceptable to clinicians within the context of the trial. The aim of this work was to develop standardised criteria for the trial entry and RFD technique for implementation within the RADICAL trial.

Methods:

Fourteen pain clinicians completed a survey, which involved reviewing the current recommendations and indicating whether they disagreed with any of the recommendations and if so why. Responses were collated and presented at a half-day workshop with 14 attendees. During the workshop, the National Low Back and Radicular Pain Pathway (NLBRPP) guidelines for patient selection and an article by Eldabe and colleagues presenting recommendations on the RFD technique were reviewed. Attendees discussed whether each component of the recommendations should be mandatory, mandatory with alteration or clarification or optional within the RADICAL trial.

Results:

Attendees agreed during the workshop that 5 of the 10 criteria for patient selection described in the NLBRPP should be mandatory within the RADICAL trial. Three were agreed as mandatory criteria but required further clarification, one of which involved defining a positive response to a diagnostic medial branch block as ⩾60% pain relief. Two criteria had optional components. After reviewing the recommendations on the RFD technique from Eldabe and colleagues, seven components were agreed as mandatory, three were mandatory with alterations and three were optional.

Conclusion:

When evaluating complex interventions, such as RFD, it is important to ensure agreement and clarity on the clinical protocol, so that the intervention can be reproduced, if found to be effective.
How partisanship and sexism influence voters’ reactions to political #MeToo scandals
Authors: Costa Mia , Briggs Trevor , Chahal Ajaipal , Fried Jonathan , Garg Rijul , Kriz Sophia , Lei Leo , Milne Anthony , Slayton Jennah
Published: July 2020

Influential theories of motivated reasoning, as well as real-world anecdotal examples, would suggest that voters do not always penalize legislators from their own party for alleged immoral behavior, such as sexual harassment. But very little empirical evidence exists on how voters react to sexual misconduct allegations, especially since the start of the #MeToo movement. We examine how partisanship and sexist attitudes shape individuals’ reactions to sexual harassment allegations about a politician. Using a pretest–posttest online experiment, we randomize both the party affiliation of the accused legislator as well as the severity of the allegations. Overall, we find some evidence of partisan bias, but that there may be a limit. Subjects were more forgiving of an accused co-partisan legislator than a legislator of the opposing party in their overall evaluation and their perceptions of punitive repercussions, but their levels of electoral support decreased just as much for co-partisans as they did for opposing partisans. Importantly, these reactions are strongly conditioned by sexism; as subjects’ levels of sexism increase, the otherwise large and negative effect of allegations on evaluations of favorability and electoral support disappears.
Governance in Public Purchasing of Tertiary-Level Health Care: Lessons From Madhya Pradesh, India
Authors: Panda Raj , Guin Pradeep , Gaurav Kumar
Published: July 2020

The performance of a health system hinges upon effective and efficient allocation of resources. The nature of governance within the health system, including critical components such as purchasing mechanism of health care services, also determines the health status of program beneficiaries. This article investigates an existing purchasing mechanism of a state-funded health care scheme through the lens of governance. We applied framework method on an adapted version of a tool developed by the World Health Organization (WHO), Organizational Assessment for Improving and Strengthening Health Financing (OASIS), to draw four themes to study the status of purchasing mechanism in Madhya Pradesh (MP), India. We used purposive sampling to select subjects from the state, district, and block levels and conducted 32 in-depth interviews. Subjects from the district and block levels were drawn from a sample of three out of 51 districts in MP. We found that although the scheme is functional, it has immense scope for improvement, thereby bettering the health outcomes of its beneficiaries.
Metastatic Calcinosis of Gastric Mucosa
Authors: Kosuru Vatsalya , Mohammed Azeem , Kapoor Rajan , Jhaveri Khushali , Medepalli Vidya , Mulloy Laura , Padala Sandeep Anand
Published: July 2020

Calcinosis cutis refers to the deposition of calcium salts in the cutaneous and subcutaneous tissue and is frequently associated with inflammation. Gastric calcinosis can be classified into metastatic, dystrophic, and idiopathic; metastatic calcinosis is the most common type. In metastatic calcification, calcium salts are deposited in normal soft tissues in the setting of altered metabolism of serum calcium and phosphorus and is a rare and serious complication of chronic renal failure. The important factors contributing to the development of metastatic calcinosis are hypercalcemia, hyperphosphatemia, and an elevated calcium-phosphate product. The most striking feature of this diagnosis is the calcification around the large joints. While it mostly involves dermis of small and medium-sized vessels, it can rarely affect the mucosal layers of the gastrointestinal (GI) tract. Calcinosis presents as a marker for the presence of calcifications in other organs, such as heart or lung, which can be life-threatening. Patients rarely present with clinical symptoms of GI upset, dyspepsia, or epigastric pain that are attributed to calcinosis. If patients present with GI symptoms, infectious causes remain to be higher on the differential. We present a case of incidental finding of gastric mucosal calcinosis during the workup and treatment of dysphagia.
Positive Cancer Experiences: Perspectives From Cancer Survivors
Authors: Fitch Margaret I , Nicoll Irene , Lockwood Gina
Published: July 2020

The purpose was to review the perspectives of cancer survivors about what they perceive constitutes positive cancer experiences. A national survey was conducted in collaboration with 10 Canadian provinces to identify experiences and unmet needs for cancer survivors between 1 and 3 years of posttreatment. The survey included open-ended questions designed to allow the respondents to add topics and details of importance. This publication presents the analysis of quantitative data and open-ended questions regarding cancer survivors’ perspectives about positive experiences and gaps in care during their cancer journey. Of the 13 534 unique adult survey respondents, 7794 (57.6%) responded to the positive experiences question and 6434 (47.5%) to the question about gaps in care. Elements of positive experiences included the compassionate health care workers, maintaining a positive outlook and the support of family and friends. Gaps in care included a lack of access to services, information, and support. Respondents were able to identify positive aspects of their cancer experiences and where improvements were needed. These findings assist in determining how health care professionals can address the needs of cancer patients based on what survivors have identified as helpful.
Popular geopolitics ‘beyond the screen’: Bringing Modern Warfare to the city
Authors: Bos Daniel
Published: July 2020

Popular culture – in this case military-themed videogames – has been argued to mould and shape popular understandings of the geopolitics of the ‘war on terror’. To date, most attention has been focused on the geopolitical representations of a ‘final’ popular cultural text or object. Less attention has been paid to how popular understandings of geopolitics and military violence have been constructed and commodified prior to, and ‘beyond the screen’. Empirically, the paper examines the marketing campaign of Call of Duty: Modern Warfare 3. Through the use of experiential marketing, I show how the game’s launch night incorporated spectacular displays, performances and consumer interactions to sell the pleasures of virtual war by drawing on geopolitical fears of terrorism and military violence within major Western cities. Firstly, I demonstrate how marketing engaged with and transformed urban spaces extending the popular geopolitics of virtual war. Secondly, the paper reveals how experiential marketing targeted and encouraged connections with and between attendees’ bodies. Thirdly, I demonstrate how such events promote geopolitical encounters which extend beyond the temporal and the spatial confines of the marketing event itself. Ultimately, the paper reveals how urban fears surrounding the global ‘war on terror’ were employed to sell the pleasures and geopolitics of virtual war.
ERS International Congress, Madrid, 2019: highlights from the Thoracic Oncology Assembly
Authors: Costantini Adrien , Bostantzoglou Clementine , Blum Torsten Gerriet
Published: July 2020

Lung cancer is a devastating disease affecting hundreds of thousands of patients in Europe. Despite recent advances in treatment, its prognosis remains poor. This is mainly attributed to the late stages that diagnoses are usually established at, consequently excluding curative treatment options. During the 2019 European Respiratory Society International Congress in Madrid, Spain, lung cancer experts presented the most recent aspects of lung cancer early detection with low-dose computed tomography.
Characterization of the effluents condensated by volatile organic compounds during heat-treated rubberwood process
Authors: Li Tongtong , Li Guanjun , Li Jianing , Li Xiaowen , Lu Quanji , Li Min
Published: July 2020

Heat treatment was an eco-friendly modification technology for rubberwood, without the addition of chemical reagents into the wood and wood performance has been improved remarkably. Many effluents are generated from heat-treated rubberwood process, which were rarely researched. The effluents contain relatively high content of volatile organic compounds, which may seriously threaten the environment and human health. In this study, effluents condensated during different heat-treated stages (125 ℃, 145 ℃, 175 ℃, 185 ℃, 215 ℃) and frequently used industrial heat treatment production technology (185 ℃/3 h, 215 ℃/3 h) were characterized by gas chromatography–mass spectrometry (GC–MS). The effluents were classified as aldehydes, phenols, esters, ketones, acids, alcohols, alkanes, anhydride, aromatics and compounds released the most during all heat-treated stages were aldehydes. With the temperature increased, the relative amounts of aldehydes decreased, while the ketones, esters and aromatics increased under acidic constituents (pH ranged from 4.17 to 2.47) and high moisture condition. The vanillin and coniferyl aldehyde accounted for much higher proportion in the aldehydes. The mass loss of rubberwood was larger under 215 ℃/3 h (16.61%), correspondingly the effluents had more kinds of compounds at 215 ℃. These results would provide guidance for research of effluent disposal and transform biomass residues into valuable things.
Machine learning based imputation techniques for estimating phylogenetic trees from incomplete distance matrices
Authors: Bhattacharjee Ananya , Bayzid Md. Shamsuzzoha
Published: July 2020

Background

With the rapid growth rate of newly sequenced genomes, species tree inference from genes sampled throughout the whole genome has become a basic task in comparative and evolutionary biology. However, substantial challenges remain in leveraging these large scale molecular data. One of the foremost challenges is to develop efficient methods that can handle missing data. Popular distance-based methods, such as NJ (neighbor joining) and UPGMA (unweighted pair group method with arithmetic mean) require complete distance matrices without any missing data.

Results

We introduce two highly accurate machine learning based distance imputation techniques. These methods are based on matrix factorization and autoencoder based deep learning architectures. We evaluated these two methods on a collection of simulated and biological datasets. Experimental results suggest that our proposed methods match or improve upon the best alternate distance imputation techniques. Moreover, these methods are scalable to large datasets with hundreds of taxa, and can handle a substantial amount of missing data.

Conclusions

This study shows, for the first time, the power and feasibility of applying deep learning techniques for imputing distance matrices. Thus, this study advances the state-of-the-art in phylogenetic tree construction in the presence of missing data. The proposed methods are available in open source form at https://github.com/Ananya-Bhattacharjee/ImputeDistances.
Integrating RNA-Seq with GWAS reveals novel insights into the molecular mechanism underpinning ketosis in cattle
Authors: Yan Ze , Huang Hetian , Freebern Ellen , Santos Daniel J. A. , Dai Dongmei , Si Jingfang , Ma Chong , Cao Jie , Guo Gang , Liu George E. , Ma Li , Fang Lingzhao , Zhang Yi
Published: July 2020

Background

Ketosis is a common metabolic disease during the transition period in dairy cattle, resulting in long-term economic loss to the dairy industry worldwide. While genetic selection of resistance to ketosis has been adopted by many countries, the genetic and biological basis underlying ketosis is poorly understood.

Results

We collected a total of 24 blood samples from 12 Holstein cows, including 4 healthy and 8 ketosis-diagnosed ones, before (2 weeks) and after (5 days) calving, respectively. We then generated RNA-Sequencing (RNA-Seq) data and seven blood biochemical indicators (bio-indicators) from leukocytes and plasma in each of these samples, respectively. By employing a weighted gene co-expression network analysis (WGCNA), we detected that 4 out of 16 gene-modules, which were significantly engaged in lipid metabolism and immune responses, were transcriptionally (FDR < 0.05) correlated with postpartum ketosis and several bio-indicators (e.g., high-density lipoprotein and low-density lipoprotein). By conducting genome-wide association signal (GWAS) enrichment analysis among six common health traits (ketosis, mastitis, displaced abomasum, metritis, hypocalcemia and livability), we found that 4 out of 16 modules were genetically (FDR < 0.05) associated with ketosis, among which three were correlated with postpartum ketosis based on WGCNA. We further identified five candidate genes for ketosis, including GRINA, MAF1, MAFA, C14H8orf82 and RECQL4. Our phenome-wide association analysis (Phe-WAS) demonstrated that human orthologues of these candidate genes were also significantly associated with many metabolic, endocrine, and immune traits in humans. For instance, MAFA, which is involved in insulin secretion, glucose response, and transcriptional regulation, showed a significantly higher association with metabolic and endocrine traits compared to other types of traits in humans.

Conclusions

In summary, our study provides novel insights into the molecular mechanism underlying ketosis in cattle, and highlights that an integrative analysis of omics data and cross-species mapping are promising for illustrating the genetic architecture underpinning complex traits.
Characterization of the bacterial communities of psyllids associated with Rutaceae in Bhutan by high throughput sequencing
Authors: Morrow Jennifer L. , Om Namgay , Beattie George A. C. , Chambers Grant A. , Donovan Nerida J. , Liefting Lia W. , Riegler Markus , Holford Paul
Published: July 2020

Background

Several plant-pathogenic bacteria are transmitted by insect vector species that often also act as hosts. In this interface, these bacteria encounter plant endophytic, insect endosymbiotic and other microbes. Here, we used high throughput sequencing to examine the bacterial communities of five different psyllids associated with citrus and related plants of Rutaceae in Bhutan: Diaphorina citri, Diaphorina communis, Cornopsylla rotundiconis, Cacopsylla heterogena and an unidentified Cacopsylla sp.

Results

The microbiomes of the psyllids largely comprised their obligate P-endosymbiont ‘Candidatus Carsonella ruddii’, and one or two S-endosymbionts that are fixed and specific to each lineage. In addition, all contained Wolbachia strains; the Bhutanese accessions of D. citri were dominated by a Wolbachia strain first found in American isolates of D. citri, while D. communis accessions were dominated by the Wolbachia strain, wDi, first detected in D. citri from China. The S-endosymbionts from the five psyllids grouped with those from other psyllid taxa; all D. citri and D. communis individuals contained sequences matching ‘Candidatus Profftella armatura’ that has previously only been reported from other Diaphorina species, and the remaining psyllid species contained OTUs related to unclassified Enterobacteriaceae. The plant pathogenic ‘Candidatus Liberibacter asiaticus’ was found in D. citri but not in D. communis. Furthermore, an unidentified ‘Candidatus Liberibacter sp.’ occurred at low abundance in both Co. rotundiconis and the unidentified Cacopsylla sp. sampled from Zanthoxylum sp.; the status of this new liberibacter as a plant pathogen and its potential plant hosts are currently unknown. The bacterial communities of Co. rotundiconis also contained a range of OTUs with similarities to bacteria previously found in samples taken from various environmental sources.

Conclusions

The bacterial microbiota detected in these Bhutanese psyllids support the trends that have been seen in previous studies: psyllids have microbiomes largely comprising their obligate P-endosymbiont and one or two S-endosymbionts. In addition, the association with plant pathogens has been demonstrated, with the detection of liberibacters in a known host, D. citri, and identification of a putative new species of liberibacter in Co. rotundiconis and Cacopsylla sp.
Calcium regulates the mycophagous ability of Burkholderia gladioli strain NGJ1 in a type III secretion system-dependent manner
Authors: Yadav Sunil Kumar , Das Joyati , Kumar Rahul , Jha Gopaljee
Published: July 2020

Background

A rice associated bacterium Burkholderia gladioli strain NGJ1 demonstrates mycophagy, a phenomenon wherein bacteria feed on fungi. Previously, we have reported that NGJ1 utilizes type III secretion system (T3SS) to deliver a prophage tail-like protein (Bg_9562) into fungal cells to establish mycophagy.

Results

In this study, we report that calcium ion concentration influences the mycophagous ability of NGJ1 on Rhizoctonia solani, an important fungal pathogen. The calcium limiting condition promotes mycophagy while high calcium environment prevents it. The expression of various T3SS apparatus encoding genes of NGJ1 was induced and secretion of several potential T3SS effector proteins (including Bg_9562) into extracellular milieu was triggered under calcium limiting condition. Using LC-MS/MS proteome analysis, we identified several calcium regulated T3SS effector proteins of NGJ1. The expression of genes encoding some of these effector proteins was upregulated during mycophagous interaction of NGJ1 with R. solani. Further, mutation of one of these genes (endo-β-1, 3- glucanase) rendered the mutant NGJ1 bacterium defective in mycophagy while complementation with full length copy of the gene restored its mycophagous activity.

Conclusion

Our study provides evidence that low calcium environment triggers secretion of various T3SS effectors proteins into the extracellular milieu and suggests the importance of cocktail of these proteins in promoting mycophagy.
WHO Trial Registration Data Set (TRDS) extension for traditional Chinese medicine 2020: recommendations, explanation, and elaboration
Authors: Zhang Xuan , Lan Liang , Chan Jacky C. P. , Zhong Linda L. D. , Cheng Chung-Wah , Lam Wai-Ching , Tian Ran , Zhao Chen , Wu Tai-Xiang , Shang Hong-Cai , Lyu Ai-Ping , Bian Zhao-Xiang
Published: July 2020

Background

Although the WHO Trial Registration Data Set (TRDS) has been published for many years, the quality of clinical trial registrations with traditional Chinese medicine (TCM) is still not satisfactory, especially about the inadequate reporting on TCM interventions. The development of the WHO TRDS for TCM Extension 2020 (WHO TRDS-TCM 2020) aims to address this inadequacy.

Methods

A group of clinical experts, methodologists, epidemiologists, and editors has developed this WHO TRDS-TCM 2020 through a comprehensive process, including the baseline survey, draft of the initial items, three-round of Delphi survey, solicitation of comments, revision, and finalization.

Results

The WHO TRDS-TCM 2020 statement extends the latest version (V.1.3.1) of TRDS published in November 2017. The checklist includes 11 extended items (including subitems), namely Source(s) of Monetary or Material Support (Item 4), Scientific Title (Item 10a and 10b), Countries of Recruitment (Item 11), Health Condition(s) or Problem(s) Studied (Item 12), Intervention(s) (Item 13a, 13b and 13c), Key Inclusion and Exclusion Criteria (Item 14), Primary and Key Secondary Outcomes (Item 19 to 20), and Lay Summary (Item B1). For Item 13 (Interventions), three common TCM interventions--i.e., Chinese herbal medicine formulas, acupuncture and moxibustion—are elaborated.

Conclusions

The group hopes that the WHO TRDS-TCM 2020 can improve the reporting quality and transparency of TCM trial registrations, assist registries in assessing the registration quality of TCM trials, and help readers understand TCM trial design.
Plasma Lipidome, PNPLA3 polymorphism and hepatic steatosis in hereditary hemochromatosis
Authors: Seeßle Jessica , Gan-Schreier Hongying , Kirchner Marietta , Stremmel Wolfgang , Chamulitrat Walee , Merle Uta
Published: July 2020

Background

Hereditary hemochromatosis (HH) is an autosomal recessive genetic disorder with increased intestinal iron absorption and therefore iron Overload. iron overload leads to increased levels of toxic non-transferrin bound iron which results in oxidative stress and lipid peroxidation. The impact of iron on lipid metabolism is so far not fully understood. The aim of this study was to investigate lipid metabolism including lipoproteins (HDL, LDL), neutral (triglycerides, cholesterol) and polar lipids (sphingo- and phospholipids), and PNPLA3 polymorphism (rs738409/I148M) in HH.

Methods

We conducted a cohort study of 54 subjects with HH and 20 healthy subjects. Patients were analyzed for their iron status including iron, ferritin, transferrin and transferrin saturation and serum lipid profile on a routine follow-up examination.

Results

HH group showed significantly lower serum phosphatidylcholine (PC) and significantly higher phosphatidylethanolamine (PE) compared to healthy control group. The ratio of PC/PE was clearly lower in HH group indicating a shift from PC to PE. Triglycerides were significantly higher in HH group. No differences were seen for HDL, LDL and cholesterol. Hepatic steatosis was significantly more frequent in HH. PNPLA3 polymorphism (CC vs. CG/GG) did not reveal any significant correlation with iron and lipid parameters including neutral and polar lipids, grade of steatosis and fibrosis.

Conclusion

Our study strengthens the hypothesis of altered lipid metabolism in HH and susceptibility to nonalcoholic fatty liver disease. Disturbed phospholipid metabolism may represent an important factor in pathogenesis of hepatic steatosis in HH.
Not so FAST. Commentary on the article “Appraisal of the faecal haemoglobin, age and sex test (FAST) score in assessment of patients with lower bowel symptoms: an observational study”
Authors: Cubiella Joaquín
Published: July 2020

A recent study by Digby et al. in BMC Gastroenterology evaluated the faecal haemoglobin, age and sex test (FAST) score in the assessment of patients with lower bowel symptoms attended in primary healthcare. This article is a valuable source of information but the conclusions must be carefully assessed. Authors evaluated the FAST score threshold with a 99% sensitivity (≥ 2.12) for colorectal cancer (CRC). Although the number of patients meeting this criteria is high, 53.5% of the patients not referred initially to secondary healthcare, the results on the patients referred to colonoscopy validate the prediction model. The sensitivity and the specificity for CRC detection were 99.0 and 23.2% with a positive and negative predictive value of 8.0 and 99.7%. Additionally, the sensitivity and the specificity for significant bowel disease were 96.1 and 26.2% with a positive and negative predictive value of 24.3 and 96.1%, consistent with our initial results. To conclude, although we need the information regarding the risk of CRC in those patients not referred to colonoscopy, a FAST Score < 2.12 allows to determine a group of patients with a low risk of CRC detection that requires no further evaluation.
Endoscopic severe mucosal atrophy indicates the presence of gastric cancer after Helicobacter pylori eradication -analysis based on the Kyoto classification
Authors: Ohno Akiko , Miyoshi Jun , Kato Atsushi , Miyamoto Naohiko , Yatagai Takahito , Hada Yu , Kusuhara Mitsunori , Jimbo Yoko , Ida Yosuke , Tokunaga Kengo , Okamoto Susumu , Hisamatsu Tadakazu
Published: July 2020

Background

Gastric cancer after Helicobacter pylori (HP) eradication is a crucial clinical challenge today as HP eradication therapy is widely performed. Detecting gastric cancer after HP eradication tends to be difficult with normal white-light endoscopy. In the present study, we aimed to identify easily-evaluated endoscopic findings that indicate the presence of gastric cancer after HP eradication so that endoscopists can consider additional detailed examinations at the site.

Methods

We analyzed the endoscopic images of 43 patients who underwent endoscopic submucosal dissection for early gastric cancer after HP eradication and 119 patients with an HP eradication history who underwent esophagogastroduodenoscopy for a medical checkup. Endoscopic findings were evaluated according to the Kyoto classification of gastritis (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness) and map-like redness.

Results

Patients with gastric cancer had significantly higher total Kyoto risk scores; more atrophy, intestinal metaplasia, and diffuse redness; and a significantly higher prevalence of map-like redness compared with those without gastric cancer, in the univariate analyses. We used logistic regression analysis with forward selection based on the likelihood ratio to develop a model using atrophy and diffuse redness. Receiver operating characteristic analysis showed that a score of A2 in the Kyoto classification of gastritis (open-type atrophic pattern in the Kimura–Takemoto classification) was an endoscopic marker for the presence of post-HP-eradication gastric cancer.

Conclusions

Endoscopic severe gastric mucosal atrophy is useful to screen patients for gastric cancer after HP eradication.
Dysbiosis, gut barrier dysfunction and inflammation in dementia: a pilot study
Authors: Stadlbauer Vanessa , Engertsberger Lara , Komarova Irina , Feldbacher Nicole , Leber Bettina , Pichler Gerald , Fink Nicole , Scarpatetti Monika , Schippinger Walter , Schmidt Reinhold , Horvath Angela
Published: July 2020

Background

Dementia is an increasing public health threat worldwide. The pathogenesis of dementia has not been fully elucidated yet. Inflammatory processes are hypothesized to play an important role as a driver for cognitive decline but the origin of inflammation is not clear. We hypothesize that disturbances in gut microbiome composition, gut barrier dysfunction, bacterial translocation and resulting inflammation are associated with cognitive dysfunction in dementia.

Methods

To test this hypothesis, a cohort of 23 patients with dementia and 18 age and sex matched controls without cognitive impairments were studied. Gut microbiome composition, gut barrier dysfunction, bacterial translocation and inflammation were assessed from stool and serum samples. Malnutrition was assessed by Mini Nutritional Assessment Short Form (MNA-SF), detailed information on drug use was collected. Microbiome composition was assessed by 16S rRNA sequencing, QIIME 2 and Calypso 7.14 tools.

Results

Dementia was associated with dysbiosis characterized by differences in beta diversity and changes in taxonomic composition. Gut permeability was increased as evidenced by increased serum diamine oxidase (DAO) levels and systemic inflammation was confirmed by increased soluble cluster of differentiation 14 levels (sCD14). BMI and statin use had the strongest impact on microbiome composition.

Conclusion

Dementia is associated with changes in gut microbiome composition and increased biomarkers of gut permeability and inflammation.Lachnospiraceae NK4A136 groupas potential butyrate producer was reduced in dementia. Malnutrition and drug intake were factors, that impact on microbiome composition. Increasing butyrate producing bacteria and targeting malnutrition may be promising therapeutic targets in dementia.

Trial registration

NCT03167983.
Reference values and sex differences in absolute and relative kidney size. A Swiss autopsy study
Authors: Kalucki Sabrina Addidou , Lardi Christelle , Garessus Jonas , Kfoury Alain , Grabherr Silke , Burnier Michel , Pruijm Menno
Published: July 2020

Background

Men have larger kidneys than women, but it is unclear whether gender remains an independent predictor of kidney size (expressed as weight or length) after correction for body size. We analysed autopsy data to assess whether relative renal length and weight (e.g. corrected for body weight, height or body surface area (BSA)) are also larger in men. Assuming that kidney size is associated with nephron number, opposite findings could partly explain why women are less prone to the development and progression of chronic kidney disease than men.

Methods

All forensic autopsies performed between 2009 and 2015 at the local university hospital of Geneva in individuals of European descent aged ≥18 years without a known history of diabetes and/or kidney disease were examined. Individuals with putrefied or severely injured bodies were excluded. Relative renal weight and length were respectively defined as renal weight divided by body weight or BSA and renal length divided by body height or BSA.

Results

A total of 635 autopsies (68.7% men) were included in the analysis. Left kidneys were on average 8 g heavier and 2 mm longer than right kidneys (both: p < 0.05). Absolute renal weight (165 ± 40 vs 122 ± 29 g) and length (12.0 ± 1.3 vs 11.4 ± 1.1 cm) were higher in men. Relative renal weight was also higher in men, but relative renal length was larger in women. In multivariable regression analysis, body height, body weight, the degree of blood congestion or depletion at autopsy and age were determinants of renal weight, whereas arterial hypertension and smoking were not. Percentile curves of renal weight and length according to sex and body height were constructed.

Conclusion

Absolute and relative renal weights were both smaller in women. This is in line with recent studies stating that nephron numbers are also lower in women. Relative renal length was longer in women, suggesting that female kidneys have a more elongated shape. In comparison with older autopsy studies, renal weight appears to be stable over time.
The predominant expression of cancer stem cell marker ALDH1A3 in tumor infiltrative area is associated with shorter overall survival of human glioblastoma
Authors: Gan Chao , Pierscianek Daniela , El Hindy Nicolai , Ahmadipour Yahya , Keyvani Kathy , Sure Ulrich , Zhu Yuan
Published: July 2020

Background

ALDH1A3 is a cancer stem cell marker in neoplasms including glioblastoma (GBM). However, the comprehensive role of ALDH1A3 in GBM remains unclear. This study attempted to investigate the expression of ALDH1A3 in human GBM tissues and its association with clinical parameters.

Methods

Thirty primary GBM and 9 control were enrolled in this study. ALDH1A3 mRNA and protein expression levels were detected by RT2-PCR and western blot, respectively. Immunohistochemistry and immunofluorescence staining were performed to evaluate the regional and cellular expression manner of ALDH1A3. The association of ALDH1A3 expression with multiple clinical parameters was analyzed.

Results

ALDH1A3 protein level, but not mRNA level, in a subgroup of GBM was significantly higher than that in the control group. ALDH1A3 immunoreactivity was detected heterogeneously in individual GBMs. Fifteen of 30 cases showed a positive of ALDH1A3 immunoreactivity which was predominantly observed in the tumor infiltrative area (TI). Double immunofluorescence staining revealed a co-localization of ALDH1A3 with GFAP in glial-shaped cells and in tumor cells. ALDH1A3 immunoreactivity was often merged with CD44, but not with CD68. Moreover, ALDH1A3 expression was positively associated with the tumor edema grade and inversely with overall survival (OS) (median OS: 16 months vs 10 months), but with neither MGMT promoter methylation status nor Ki67 index in GBM. An upregulation of ALDH1A3 was accompanied by a reduced expression of STAT3β and p-STAT3β.

Conclusions

Inter- and intra-tumoral heterogeneous expression of ALDH1A3 was exhibited in GBMs. A high immunoreactivity of ALDH1A3 in tumor infiltrative area was associated with shorter OS, especially in patients with MGMT promoter methylation. Our findings propose ALDH1A3 not only as a predictive biomarker but also as a potential target for personalized therapy of GBM.
The expression and significance of mTORC1 in diabetic retinopathy
Authors: Liu Yanli , Zheng Yarong , Zhou Yekai , Liu Yi , Xie Mengxuan , Meng Wenjing , An Meixia
Published: July 2020

Background

To investigate the expression and significance of mechanistic target of rapamycin complex 1(mTORC1) in diabetic retinopathy (DR), and to find new targets and new methods for the treatment of DR.

Methods

A DR rat model was prepared by general feeding combined with intraperitoneal injection of 10% streptozotocin (60 mg/kg). The rats were randomly divided into a control group (NDM group) and a diabetes group (DM group). Three months later, the degrees of retinopathy was determined using hematoxylin and eosin staining, and the levels of p-S6, VEGF, and PEDF proteins were detected by immunohistochemistry and western blotting. Human retinal capillary endothelial cells (HRCECs) were cultured in high glucose (HG) conditions, then treated with rapamycin or transfected with siTSC1.The protein levels of p-S6 were assessed by western blotting. The 5-ethynyl-2′-deoxyuridine assay was used to detect cell proliferation, and the Transwell assay was used to detect cell migration.

Results

A DM rat model was successfully developed. The expressions of p-S6 and VEGF proteins were significantly increased in the DM group (p < 0.05), and the expression of PEDF protein was significantly decreased compared with the NDM group (p < 0.05). In vitro, the p-S6 protein, as well as cell proliferation and migration, in HG induced HRCECs were increased (p < 0.05) compared with the control (normal glucose) group (p < 0.05). After transfection with siTSC1 to activate mTORC1, the expression of p-S6, as well as cell proliferation and migration, were increased. In contrast, rapamycin decreased p-S6 expression, as well as proliferation and migration, in HG induced HRCECs compared to the control group (p < 0.05).

Conclusion

mTORC1 plays an important role in DR. After activation, mTORC1 induced expression of the p-S6 protein, regulated the expressions of VEGF and PEDF proteins, and changed the proliferation and migration of endothelial cells. The mTORC1 can therefore be used as a new target,as well as in the treatment of DR.
Influence of pupil dilation on the Barrett universal II (new generation), Haigis (4th generation), and SRK/T (3rd generation) intraocular lens calculation formulas: a retrospective study
Authors: Teshigawara Takeshi , Meguro Akira , Mizuki Nobuhisa
Published: July 2020

Background

Despite the surge in the number of cataract surgeries, there is limited information available regarding the influence of pupil dilation on predicted postoperative refraction and its comparison with recommended various intraocular lens power calculated using the different parameters. We used three different IOL power calculation formulas: Barrett Universal II (Barrett) (5-variable formula), Haigis (3-variable formula), and SRK/T (2-variable formula), in order to investigate the potential effect of pupil dilation on the predicted postoperative refraction (PPR) and recommended intraocular lens (IOL) power calculation.

Methods

This retrospective study included 150 eyes. All variables were measured and calculated using a ZEISS IOL Master 700. The following variables were measured before and after dilation: anterior chamber depth (ACD), lens thickness (LT), white-to-white (WTW). PPR and recommended IOL power were calculated by Barrett, Haigis, and SRK/T IOL calculation formulas. The change in each variable before and after dilation, and the correlations between all changes were analyzed using the Wilcoxon signed-rank test and the Spearman’s rank-order correlation test, respectively.

Results

The mean absolute change (MAC) in PPR before and after dilation was found to be highest in the Barrett formula. Significant differences were found between each MAC (P <  0.0001). Significant changes were observed before and after dilation in ACD and LT (P <  0.0001), but not in WTW. Using the Barrett and Haigis formulas, there was a significant positive correlation between the change in PPR and change in ACD (P <  0.0001), and a negative correlation between change in PPR and change in LT (P <  0.0001). The correlations were strongest with the Barret formula followed by the Haigis, particularly in terms of LT. Changes in PPR determined by the Barrett formula also demonstrated a significant positive correlation with changes in WTW (P = 0.022). The recommended IOL power determined using Barrett and Haigis changed before and after dilation in 23.3 and 19.3% cases respectively, while SRK/T showed no change.

Conclusions

In terms of PPR and recommended IOL power, pupil dilation influenced mostly the Barrett formula. Given the stronger correlation between the changes in PPR when using Barrett and the changes in ACD, LT, and WTW, changes in ACD, LT, and WTW significantly affect how dilation influences the Barrett formula. Determining how dilation influences each formula and other variables is key to improving the accuracy of IOL calculations.