bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased the risk of depression in patients with chronic rhinosinusitis without polyp
Authors: Choi Hyo Geun , Hong Seok Jin , Han Juho , Park Chan Hum , Lee Joong Seob
Published: May 2020

Previous studies have reported that chronic rhinosinusitis (CRS) is closely related to depression. The present study aims to elucidate the association between CRS without nasal polyp and depression using a national sample cohort. Using the national sample cohort from Korean Health Insurance Review and Assessment Service, we matched patients with CRS (n = 21,707) to control participants (n = 86,828), at a ratio of 1:4, according to age, sex, household income, region of residence. The stratified Cox proportional-hazards model was used to evaluate the hazard ratio (HR) between CRS and depression. A subgroup analysis was performed according to age group and gender. The HR for depression was significantly higher in patients with CRS than in control participants (adjusted HR = 1.41, 95% confidence interval = 1.33–1.48) after adjustment for age, sex, household income, region of residence, and medical history. The risk of depression was also elevated in the subgroup analysis, regardless of age or gender. In conclusion, CRS was significantly associated with the increased risk of depression.
Efficacy of telbivudine and entecavir against virus reactivation in HBeAg−patients undergoing chemotherapy
Authors: Chen Chih-Jen , Yu Hsien-Chung , Chang Chen-Wang , Bair Ming-Jong , Lin Ching-Chung , Lin Yang-Sheng , Cai Zong-Sian , Chen Ming-Jen
Published: May 2020

The renal protective effect of telbivudine (LdT) was verified by a previous meta-analysis. It was left unclear, however if this effect offsets the associated risk of virological breakthrough in hepatitis B e-antigen-negative (HBeAg−) patients receiving chemotherapy (C/T).

Records of 260 HBeAg−, non-cirrhotic cancer patients undergoing systemic C/T with prophylactic LdT or entecavir (ETV) were retrospectively investigated. The investigation was conducted 6 months after completion of C/T, patient death from cancer, or antiviral modification. Treatment duration, outcome, change of renal function, and reason for antiviral modification were analyzed. The primary endpoint was the occurrence of virological breakthrough during prophylaxis C/T and the change in renal function.

Of the 126 HBeAg− patients treated with LdT, 3 (2.38%) experienced HBV virological breakthroughs, whereas none of the patients treated with ETV (P = .07) did. The estimated glomerular filtration rate for the patients treated with LdT was essentially unaltered, decreasing only slightly from 87.5 ± 23.1 to 87.3 ± 21.3 ml/minute/1.73 m2 (P = .55), while the rate for the ETV-treated patients was significantly lowered from 95.7 ± 32.2 to 85.5 ± 85.7 ml/minute/1.73 m2 (P = .0009).

The absolute risk reduction ARR is 27.8% − 21.2% = 6.6%, comparing ETV with LdT for reduction of renal function impairment and the absolute risk increase for virological breakthrough during C/T, the absolute risk increase (ARI) is 2.38% − 0% = 2.38%. The overall likelihood of being helped over being harmed was 2.77. With careful selection of patients with the criteria of HBeAg−status and non-hematologic cancer, it is feasible that telbivudine raise lower probability of virological breakthroughs during prophylaxis treatment.
Upper airway obstruction during extubation after general anesthesia, in a patient with Parkinson disease
Authors: Sun Xiaodi , Dai Leyang , Pan Yinbing , Sha Huanhuan
Published: May 2020

Rationale:

Parkinson disease (PD) is a chronic neurodegenerative condition often suffered by the elderly. Upper airway obstruction, though rare in patients with PD, can be life threatening and is associated with vocal cord paralysis, laryngeal spasm, and dystonia of jaw and neck muscles.

Patient concerns:

We describe a life-threatening upper airway obstruction caused by bilateral vocal cord paralysis, in an elderly man with PD, during extubation after general anesthesia.

Diagnoses:

Based on clinical presentation and visual laryngoscopy, the patient was diagnosed with laryngeal spasm and bilateral vocal cord paralysis after extubation.

Interventions:

Re-intubation was carried out and dopamine hydrazine tablets were administered via a nasal feeding tube.

Outcomes:

After re-intubation and further treatment, the endotracheal tube was successfully removed and no symptoms of respiratory distress were observed.

Lessons:

Patients with PD may be at a risk of life-threatening upper airway obstruction after extubation, which should be prevented systematically.
Efficacy of prostaglandina E1 for the treatment of patients with thrombo-occlusive vasculitis
Authors: Sun Yao , Wang Han-rui , Feng Xiao-hang , Wang Kai-feng
Published: May 2020

Background:

This study aims to explore the efficacy and safety of prostaglandina E1 (PE1) for the treatment of patients with thrombo-occlusive vasculitis (TOV).

Methods:

Electronic databases (Cochrane Library, PUBMED, EMBASE, Web of Science, Scopus, the Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure) will be sought from onset to the March 1, 2020 without language and publication status restrictions. We will include any potential randomized controlled trials that examined the efficacy of PE1 for the treatment of patients with TOV. We will appraise study quality using Cochrane risk of bias tool, and will assess the evidence quality using Grading of Recommendations Assessment Development and Evaluation. We will use RevMan 5.3 Software for statistical analysis.

Results:

A high-quality synthesis of present evidence of PE1 for the treatment of patients with TOV will be provided in this study.

Conclusion:

This study will provide evidence to judge whether PE1 is an effective intervention for TOV.

Systematic review registration:

INPLASY202040081.
Removal of the root canal smear layer using Carisolv III and sodium hypochlorite
Authors: Wu Di , Ma Yong-zhen , Jia Jing , Xin Bing-chang , Wang Da-shan , Sun De-gang , Wang Ling-xiang
Published: May 2020

The present study investigated the effectiveness of a Carisolv III + 0.5% sodium hypochlorite (NaOCl)-based root canal irrigant for smear layer removal.

Forty maxillary incisors were randomly divided into 4 groups (n = 10 per group). The canals in group A (experimental) were prepared with 0.5% NaOCl, and Carisolv III and 0.5% NaOCl was used for the final washing; groups B and C (positive controls) used 2% and 5.25% NaOCl, respectively; and group D (negative control) used phosphate-buffered saline (PBS). Ethylenediaminetetraacetic acid (EDTA) was used for all of the groups. A 5-point scoring scale and scanning electron microscopy were used to evaluate the effectiveness of the irrigants. The canals were consistently cleaner in the coronal and middle thirds than in the apical thirds (P < .05).

For cleaning the root canals, 5.25% NaOCl was more effective than 2% NaOCl, 0.5% NaOCl + Carisolv III, and phosphate-buffered saline , respectively (P < .05). The 2% NaOCl solution showed similar results to 0.5% NaOCl + Carisolv III (P > .05). The combination of 5.25% NaOCl and 17% EDTA remains the most effective irrigant for removal of the root canal smear layer.

A combination of Carisolv III + 0.5% NaOCl (with 17% EDTA) showed a cleaning ability similar to that of 2% NaOCl (with 17% EDTA).
Acupuncture and manual therapy for rotator cuff tears
Authors: Tang Hongzhi , Luo Fei , Fan Huaying , Huang Li , Liao Shichuan , Yu Wenjing , Chen Yunbei , Qin Xuefei , Chen Jiao
Published: May 2020

Background:

The tears of rotator cuff is caused by the tears or aseptic inflammation of tendon tissue such as subscapular muscle, supraspinatus muscle, infraspinatus muscle, teres minor muscle, and so on, which make up the rotator cuff. Managements of rotator cuff disease often include acupuncture and manual therapy, usually delivered together. The aim of this review is to assess the effectiveness and safety of such interventions in patients with pain and dysfunction caused by rotator cuff tears.

Methods:

We will search the EMBASE, the Cochrane Library, Ovid MEDLINE, PubMed, Web of Science, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Wanfang Database, the Chongqing VIP, the US National Institute of Health, the NIH clinical registry Clinical Trials, the International Clinical Trials Registry Platform, the Australian New Zealand Clinical Trials Registry and the Chinese clinical registry, from their inception to April 1, 2020. Randomized controlled trials that include patients with rotator cuff tears receiving acupuncture and manual therapy versus a control group will be included. The selection of studies, data extraction and risk of bias assessment will be conducted by 2 independent researchers. A third review author will resolve disagreements. The dichotomous data will be presented as risk ratios with 95% CIs and the continuous data will be presented as weighted mean differences or standardized mean differences with 95% CIs. Evidence quality will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation system.

Discussion:

This systematic review will provide updated evidence of various types of acupuncture and manual therapy specifically focuses on its effectiveness and safety for patients’ pain and dysfunction caused by rotator cuff tears.

Ethics and dissemination:

Ethical approval is not necessary as this review will not require data from individual patients. The results of this will be published through peer-reviewed journal articles or conference presentations.

Registration:

Open Science Framework Preregistration. Registration number 10.17605/OSF.IO/M3NKV.
Acquired reactive perforating collagenosis
Authors: Zhang Xinyue , Yang Yan , Shao Shiying
Published: May 2020

Introduction:

Acquired reactive perforating collagenosis (ARPC) is a rare skin disorder, which is associated with various internal diseases and even malignant neoplasms. A comprehensive knowledge of the concomitant diseases in ARPC patients is helpful to decrease the misdiagnosis. Although the treatment of ARPC is challenging, systemic assessment of existing regimens is not available.

Patient concerns:

A 50-year-old woman was admitted to the hospital due to cutaneous pruritus and papules all over the body.

Diagnosis:

Physical examination showed various sized papules on the lower limbs, buttocks, back, chest, and upper arms with keratotic plugs in the center. Histopathology showed typical collagenous fiber perforation. The diagnosis of ARPC was made according to histopathology, onset age and typical skin lesions. Type 2 diabetes mellitus (T2DM), chronic renal failure (CRF), and hypothyroidism simultaneously presented in this patient.

Interventions:

This patient was initially treated with topical corticosteroids and oral antihistamines for the skin lesion and pruritus. Medications for glucose control and recovery of renal and thyroid functions were also applied. On the second admission, the combined therapy of topical retinoic acid, Chinese medicinal herb-Qingpeng ointment, and Zinc oxide ointment was added.

Outcomes:

Papules and pruritus were improved significantly after the second hospitalization.

Conclusion:

We present a case of ARPC associated with T2DM, CRF, and hypothyroidism, which has rarely been described. There is no standardized treatment for ARPC. Co-administration of two or more agents for dermatologic interventions and treatment for associated diseases may help to improve skin symptoms.
A global bibliometric and visualized analysis in the status and trends of subchondral bone research
Authors: Mao Xingjia , Chen Chenglong , Wang Bin , Hou Jie , Xiang Chuan
Published: May 2020

Background:

Structural and functional changes in subchondral bone have been recognized as a key factor in the development of related disease, and subchondral bone may be a new target for the treatment of osteoarthritis. The purpose of our present study is to investigate the global status and trends of subchondral bone research.

Method:

Publications related to the studies of subchondral bone from 1993 to 2018 were retrieved from the Science Citation Index-Expanded Web of Science database. The data source was studied and indexed by using bibliometric methodology. For visualized study, bibliographic coupling analysis, co-authorship analysis, co-citation analysis, co-occurrence analysis and the analysis of publication trends in subchondral bone research were conducted by VOS viewer and GraphPadPrism 5 software.

Results:

A total of 4780 publications were included. There is an increasing trend of the relative research interests and number of publications per year globally. The cumulative number of publications about subchondral bone research followed the logistic growth model

JOURNAL/medi/04.03/00005792-202005290-00077/inline-graphic1/v/2024-03-08T181526Z/r/image-tiff

. The USA made the highest contributions to the global research with the most citations, the highest H-index, and the most total link strength, while Denmark had the highest average citation per item. The journal Osteoarthritis and Cartilage had the largest publication number. Boston University is the most contributive institution. Studies could be divided into 4 clusters: “Mechanism research”, “Animal study”, “Clinical study” and “Pathological features”. Less efforts were put into clinical study.

Conclusion:

The number of publications about subchondral bone research would be increasing in the next years based on the current global trends. Attention should be drawn to the latest popular research, including “Mesenchymal stem-cells”, “Autologous chondrocyte implantation”, “Microfracture” and “Pain”. Therefore, more and more efforts will be put into mechanism research on subchondral bone, which may inspire new clinical treatments for osteoarthritis and other related diseases based on subchondral bone.
Canaloplasty for the treatment of primary open-angle glaucoma
Authors: Sun Peng , Liu Hong-wei , Zhou Ping-ping , Meng Yan
Published: May 2020

Background:

Canaloplasty has been reported to manage primary open-angle glaucoma (POAG) effectively. However, no study has specifically and systematically investigated the efficacy and safety of canaloplasty for the treatment of POAG. Thus, this study will systematically and comprehensively appraise the efficacy and safety of canaloplasty for the treatment of POAG.

Methods:

MEDLINE, EMBASE, Cochrane Library, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be sought from the construction to the February 29, 2020. Only randomized controlled trials (RCTs) focusing on canaloplasty for the treatment of POAG will be included. Two reviewers will independently undertake selection of study, data extraction, and risk of bias assessment. Any doubts between 2 reviewers will be resolved through discussion with another experienced reviewer. RevMan 5.3 software will be employed for data analysis.

Results:

This study will summarize high-quality RCTs on investigating efficacy and safety of canaloplasty for the treatment of POAG.

Conclusion:

The findings of this study will help to determine whether canaloplasty is effective and safety for the treatment of POAG.

Systematic review registration: INPLASY202040119.
Isokinetic back training is more effective than core stabilization training on pain intensity and sports performances in football players with chronic low back pain
Authors: Nambi Gopal , Abdelbasset Walid Kamal , Alqahtani Bader A. , Alrawaili Saud M. , Abodonya Ahmed M. , Saleh Ayman K.
Published: May 2020

Background:

Isokinetic training (IKT) and core stabilization training (CST) are commonly used for balance training in musculoskeletal conditions. The knowledge about the effective implementation of these training protocols on sports performances in university football players with chronic low back pain (LBP) is lacking.

Objective:

To find and compare the effects of IKT and CST on sports performances in university football players with chronic LBP.

Design:

Randomized, double-blinded controlled study.

Setting:

University hospital.

Participants:

Sixty LBP participants divided into isokinetic group (IKT; n = 20), core stabilization group (CST; n = 20), and the control group (n = 20) and received respected exercises for 4 weeks.

Outcome measures:

Clinical (pain intensity and player wellness) and sports performances (40 m sprint, 4 × 5 m sprint, submaximal shuttle running, counter movement jump, and squat jump) scores were measured at baseline, after 4 weeks, 8 weeks, and 3 months.

Results:

Four weeks following training IKT group shows more significant changes in pain intensity and player wellness scores than CST and control groups (P ≤ .001). Sports performance variables (40 m sprint, 4 × 5 m sprint, submaximal shuttle running, counter movement jump and squat jump) scores also show significant improvement in IKT group than the other 2 groups (P ≤ .001).

Conclusion:

This study suggests that training through IKT improves pain intensity and sports performances than CST in university football players with chronic LBP.
Exercise adherence in breast cancer patients
Authors: Tao Lin , Wang Miaowei , Zhang Xiaoxia , Du Xinwen , Fu Lan
Published: May 2020

To describe social support, self-efficacy, and exercise adherence and to measure the correlations among these factors in postoperative breast cancer patients in Southwest China.

Social support, self-efficacy, and exercise adherence are interacting factors that contribute to physical and mental health and quality of life. Little is known about the status of these factors in Southwest China, and little research has explored the relationships among them.

Using a stratified sampling method, we selected patients who underwent modified radical mastectomy in 20 secondary and tertiary comprehensive hospitals in Southwest China. A descriptive cross-sectional study was conducted. Questionnaires were given to 632 breast cancer patients who met the inclusion and exclusion criteria (from August 2018 to February 2019). The questionnaire included the following 4 sections: general information, perceived social support scale, strategies used by people to promote health, and postoperative functional exercise adherence scale. Structural equation modeling was used to evaluate the hypothesized relationships among social support, self-efficacy, and exercise adherence.

The level of social support of postoperative patients with breast cancer in Southwest China was high (63.43 ± 9.25); however, levels of self-efficacy (95.00 ± 18.81) and exercise adherence (49.07 ± 10.57) were moderate. Higher social support correlated with higher exercise adherence (r = 0.526, P < .01). Higher self-efficacy was also correlated with higher exercise adherence (r = 0.427, P < .01). In-home support, out-of-home support, and self-efficacy had direct positive effects on exercise adherence (β = 0.37, P < .01; β = 0.23, P < .01; and β = 0.32, P < .01, respectively); in-home support indirectly affected exercise adherence through self-efficacy (β = 0.58, P < .01).

Social support and self-efficacy correlated highly with exercise adherence. It is recommended that attention be paid to the development of self-efficacy and social support during postoperative rehabilitation to improve the exercise adherence of postoperative breast cancer patients.
Identification of biomarkers of clear cell renal cell carcinoma by bioinformatics analysis
Authors: Zhang Ning , Chen Wenxin , Gan Zhilu , Abudurexiti Alimujiang , Hu Xiaogang , Sang Wei
Published: May 2020

Clear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer, and more and more researches find that the occurrence of ccRCC is associated with genetic changes, but the molecular mechanism still remains unclear. The present study aimed to identify aggregation trend of differentially expressed genes (DEGs) in ccRCC, which would be beneficial to the treatment of ccRCC and provide research ideas using a series of bioinformatics approach. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) analysis were used to get the enrichment trend of DEGs of GSE53757 and GSE16449. Draw Venn Diagram was applied for co-expression of DEGs. Cytoscape with the Retrieval of Interacting Gene (STRING) datasets and Molecular Complex Detection (MCODE) were performed protein-protein interaction (PPI) of DEGs. The Kaplan–Meier Plotter analysis of top 15 upregulated and top 15 downregulated were selected in Gene Expression Profiling Interactive Analysis (GEPIA). Then, the expression level of hub genes between normal renal tissue and different pathological stages of ccRCC tissue, which significantly correlated with overall survival in ccRCC patients, were also analyzed by Ualcan based on The Cancer Genome Atlas (TCGA) database. In this study, we got 167 co-expression DEGs, including 72 upregulated DEGs and 95 downregulated DEGs. We identified 11 hub genes had significantly correlated with overall survival in ccRCC patients. Among them, KIF23, APLN, ADCY1, GREB1, TLR4, IRF8, CXCL1, CXCL2, deserved our attention.
Case report of a familial triple: a syndrome and review of the literature
Authors: Gaiani Federica , Gismondi Pierpacifico , Minelli Roberta , Casadio Giovanni , de’Angelis Nicola , Fornaroli Fabiola , de’Angelis Gian Luigi , Manfredi Marco
Published: May 2020

Rationale:

Triple-A syndrome, or Allgrove syndrome (AS), is a rare autosomal recessive disorder characterized by the alacrimia, achalasia, and adrenal insufficiency triad. Alacrimia usually starts at early infancy, while achalasia and adrenal insufficiency appear later during childhood or adulthood. Some patients may also present with the so-called Double-A syndrome (i.e., alacrimia and achalasia, or alacrimia and adrenal insufficiency); adrenal insufficiency usually represents a life-threatening event due to severe hypoglycemia. Many patients may also present other associated manifestations, such as neurological disorders. We describe, here, 2 sisters of non-consanguineous parents.

Patient concerns:

An 8-year-old girl was admitted to the Pediatric Care Unit of Parma after an episode characterized by seizure with loss of consciousness and generalized hypertonia lasting a few minutes. Her sister, a 6-year-old girl, presented with recurrent episodes of vomiting and failure to thrive.

Diagnoses:

Both children were investigated by laboratory tests, esophagogastroduodenoscopy, and imaging. The first patient had the complete triad of AS (alacrimia, achalasia, adrenal insufficiency), while the second one presented only alacrimia and achalasia. Both resulted from a mutation in the achalasia, addisonianism, alacrimia syndrome gene.

Interventions:

Both patients were treated with oral hydrocortisone for Addison disease, and with artificial tears in the first case. After many pneumatic endoscopic dilations and therapy with nifedipine, both patients underwent surgical Heller myotomy for achalasia.

Outcomes:

A rapid and favorable recovery to normal diet and with improvement of growth parameters was obtained. These cases are also compared with the literature data, reported in a brief review.

Lessons:

AS is a rare multisystemic disorder. The longer diagnosis is delayed, the greater extent to which this syndrome may be life-threatening, mainly because of hypoglycemia due to adrenal insufficiency. In AS, the red-flag symptom of alacrimia should instigate investigation for achalasia, Addison disease, and achalasia, addisonianism, alacrimia syndrome gene mutation.
Safety and efficacy of Chinese herbal bath for psoriasis vulgaris
Authors: Lin Wenxia , Yu Qianying , Qin Yuesi , Xiao Jianhua , Peng Li , Zhang Jie , He Jia , Xiang Haoyu , Xiao Min , Chen Mingling
Published: May 2020

Background:

Psoriasis is a common, chronic, and recurrent skin inflammatory disease, with psoriasis vulgaris considered as the most prevalent type of psoriasis. Chinese herbal bath, a type of traditional Chinese medicine, is an external therapy widely used to treat psoriasis vulgaris in China, and it has achieved satisfactory clinical effects. However, there are few studies evaluating the safety and efficacy of Chinese herbal bath compared with other external therapies administered under similar conditions. The purpose of this study is to comprehensively evaluate the clinical safety and efficacy of Chinese herbal bath in the treatment of psoriasis vulgaris through a systematic evaluation of the literature, so as to provide a reference basis for future clinical applications.

Methods:

PubMed, Embase, CENTRAL, the Web of Science, the China Biology Medicine Database (CBM), the China National Knowledge Database (CNKI), the Wan Fang Database, and the Chong Qing VIP Database will be searched to collect randomized controlled trials of Chinese herbal bath used to treat psoriasis vulgaris. The search time limits will be from the establishment of the database to December 2019. Two researchers will independently screen the studies, extract data, and evaluate the risk of bias of the studies. Meta-analysis will be carried out with the RevMan5.3 software. The mean difference will be used as the effect index for the measurement data, and the odds ratio will be used as the effect index for the enumeration data. The 95% confidence interval will be provided for each effect. Heterogeneity among the results of each study will be evaluated by the Chi-square test.

Results:

This study will comprehensively evaluate the clinical safety and efficacy of Chinese herbal bath in the treatment of psoriasis vulgaris, so as to provide a reference basis for future clinical applications.

Conclusion:

This study will provide a theoretical basis for the standardized administration of Chinese herbal bath.

OSF registration number:

doi: 10.17605/OSF.IO/4HRPJ
Total bile acid to platelet ratio
Authors: Jiang Minjie , Yan Xin , Song Xinyue , Yan Qi , Zhao Youyou , Wang Luyuan , Gao Pujun
Published: May 2020

The aim of the study was to develop a new early noninvasive diagnostic model for primary biliary cholangitis (PBC).

A total of 118 PBC patients who had undergone a liver biopsy were enrolled in the study, and were randomized into a model group (78 patients) and a validation group (40 patients). The patients’ histological stages were based on the classifications of the Scheuer's stage. All common parameters and liver pathological results were analyzed. And total bile acid to platelet ratio, aspartate aminotransferase to platelet ratio index, fibrosis index based on 4 factors and red cell distribution width to platelet ratio were calculated.

There were 106 (89.8%) women and 12 men in this study, and the number of patients in Scheuer stage I, II, III, and IV hepatic fibrosis was 52 (44.1%), 36 (30.5%), 26 (22.0%), and 4 (3.4%), respectively. The areas under the receiver operating characteristic curves of the total bile acid to platelet ratio (TPR), the aspartate aminotransferase to platelet ratio index, the fibrosis index based on 4 factors , and the red cell distribution width to platelet ratio for predicting advanced liver fibrosis were 0.771, 0.715, 0.618, and 0.517 respectively. The areas under the receiver operating characteristic curves of the TPR was higher than other non-invasive serological models.

As a simple, inexpensive and easily accessible non-invasive liver fibrosis diagnostic model, the TPR may be a new noninvasive marker for predicting histologic severity of PBC.
Protective effects of Helicobacter pylori membrane vesicles against stress and antimicrobial agents
Authors: Murray Benjamin Oliver , Dawson Robin Andrew , Alsharaf Lolwah Mohammad , Anne Winter Jody
Published: May 2020

Outer-membrane vesicles (OMVs) produced by

Helicobacter pylori

deliver bacterial components to host cells, provide a mechanism for stabilization of secreted components and may allow the bacteria to exert ‘long-range’ effects in the gastric niche, promoting persistence. In addition to their well-characterized host cell interactions, membrane vesicles improve stress survival in other bacterial species, and are constitutively produced by both pathogenic and non-pathogenic bacteria. We aimed to determine whether OMVs could improve

H. pylori

survival of a range of stressors. The effects of purified OMVs on the resistance of

H. pylori

to a range of environmental and antimicrobial stresses were determined using growth curves and survival assays. Addition of purified OMVs to

H. pylori

cultures provided dose-dependent protection against hydrogen peroxide-mediated killing. Supplementation with OMVs also partially protected

H. pylori

against the bactericidal effects of the antibiotics clarithromycin and levofloxacin, but not against amoxicillin nor metronidazole. Addition of purified OMVs allowed

H. pylori

to grow in the presence of inhibitory concentrations of the antimicrobial peptide LL-37. In the presence of 50 µg OMVs ml−1, significantly enhanced

H. pylori

growth was observed at higher LL-37 concentrations compared with lower LL-37 concentrations, suggesting that OMV–LL-37 interactions might facilitate release of growth-promoting nutrients. Taken together, these data indicate that production of membrane vesicles could help

H. pylori

to survive exposure to antibiotics and host antimicrobial defences during infection.
HLAssign 2.0: An advanced Graphical User Interface for the analysis of short and long read Human Leukocyte Antigen-typing data
Authors: Wittig M , Schmöhl M , Koch S , Ziemann M , Görg S , Lange V , Jacob F , Forster M , Franke A
Published: May 2020

Next Generation Sequencing (NGS) based Human Leukocyte Antigen (HLA) typing has been a challenge due to the polymorphism of the HLA region. Nevertheless, the method’s accuracy has increased during the last years and it is now routinely used by many large centers including bone marrow registries. However, challenging HLA genotype compositions exist, which hinder a fully automated analysis. Therefore, HLA typing results are still visually inspected in diagnostics, i.e. the underlying read mappings and phasing information is controlled. Here, we present HLAssign 2.0 that now includes a strict workflow, improved tools for visual inspection and read phasing analysis in the automatic caller. In collaboration with interface design researchers, biologists and informaticians we developed an elaborate graphical user interface for visual evaluation of automated HLA calls for Illumina NGS reads. We also provide tools to preprocess 10x Genomics and PacBio sequencing reads for HLAssign analysis. We benchmarked our automatic caller against STC-seq and xHLA, showing comparable automatic call rates. Additional manual inspection of the automatic results in our GUI assists the user to assign the correct HLA calls and to achieve diagnostic accuracy. HLAssign 2.0 is free for research and commercial use and is available for Windows and MacOS.
Time-course Profiling of Bovine Herpesvirus Type 1 and Host Cell Transcriptomes using Multiplatform Sequencing
Authors: Moldován Norbert , Maróti Zoltán , Torma Gábor , Gulyás Gábor , Hornyák Ákos , Zádori Zoltán , Jefferson Victoria A. , Csabai Zsolt , Boldogkői Miklós , Kalmár Tibor , Tombácz Dóra , Meyer Florencia , Boldogkői Zsolt
Published: May 2020

Long-read sequencing (LRS) has become a standard approach for transcriptome analysis in recent years. This technology is also used for the identification and annotation of genes of various organisms, including viruses. Bovine herpesvirus type 1 (BoHV-1) is an important pathogen of cattle worldwide. However, the transcriptome of this virus is still largely unannotated. This study reports the profiling of the dynamic lytic transcriptome of BoHV-1 using two long-read sequencing (LRS) techniques, the Oxford Nanopore Technology (ONT) MinION, and the Illumina LoopSeq synthetic LRS methods, using multiple library preparation protocols. In this work, we annotated viral mRNAs and non-coding transcripts, and a large number of transcript isoforms, including transcription start and end sites, as well as splice variants of BoHV-1. Very long polycistronic and complex viral transcripts were also detected. Our analysis demonstrated an extremely complex pattern of transcriptional overlaps formed by transcriptional read-throughs or overlapping the 5’-untranslated regions of divergently-oriented transcripts. The impact of the viral infection on the host cell transcriptome was also assessed. Our results demonstrate that genes associated with antiviral response as well as viral transcription and translation are upregulated.
Common substructures and sequence characteristics of sandwich-like proteins from 42 different folds
Authors: Kister A.E.
Published: May 2020

This study addresses the following fundamental question: Do sequences of protein domains with sandwich architecture have common sequence characteristics even though they belong to different superfamilies and folds? The analysis was carried out in two stages: determination of substructures in the domains that are common to all sandwich proteins; and detection of common sequence characteristics within the substructures. Analysis of supersecondary structures in domains of proteins revealed two types of four-strand substructures that are common to sandwich proteins. At least one of these common substructures was found in proteins of 42 sandwich-like folds (as per structural classification in the CATH database). Comparison of the sequence fragments corresponding to strands that make up the common substructures revealed specific rules of distribution of hydrophobic residues within these strands. These rules can be conceptualized as grammatical rules of beta protein linguistics. Understanding of the structural and sequence commonalities of sandwich proteins may also be useful for rational protein design.
Finding disease modules for cancer and COVID-19 in gene co-expression networks with the Core&Peel method
Authors: Lucchetta M. , Pellegrini M.
Published: May 2020

Diseases imply dysregulation of cell’s functions at several levels. The study of differentially expressed genes in case-control cohorts of patients is often the first step in understanding the details of the cell’s dysregulation. A further level of analysis is introduced by noticing that genes are organized in functional modules (often called pathways), thus their action and their dysregulation may be better understood by the identification of the modules most affected by the disease (aka disease modules, or active subnetworks). We describe how an algorithm based on the Core&Peel method developed originally for detecting protein complexes in PPI networks, can be adapted to detect disease modules in co-expression networks of genes. We first validate Core&Peel for the easier general task of functional module detection by comparison with 42 methods participating in the Disease Module Identification DREAM challenge of 2019. Next, we use four specific disease test cases (colorectal cancer, prostate cancer, asthma and rheumatoid arthritis), four state-of-the-art algorithms (ModuleDiscoverer, Degas, KeyPathwayMiner and ClustEx), and several pathway databases to validate the proposed algorithm. Core&Peel is the only method able to find significant associations of the predicted disease module with known validated relevant pathways for all four diseases. Moreover for the two cancer data sets, Core&Peel detects further nine relevant pathways enriched in the predicted disease module, not discovered by the other methods used in the comparative analysis. Finally we apply Core&Peel, along with other methods, to explore the transcriptional response of human cells to SARS-CoV-2 infection, at a modular level, aiming at finding supporting evidence for drug repositioning efforts.
Tumor-on-a-chip platform to interrogate the role of macrophages in tumor progression
Authors: Bi Ye , Shirure Venktesh S. , Liu Ruiyang , Cunningham Cassandra , Ding Li , Meacham J. Mark , Goedegebuure S. Peter , George Steven C. , Fields Ryan C.
Published: May 2020

Tumor-infiltrating leukocytes, in particular macrophages, play an important role in tumor behavior and clinical outcome. The spectrum of macrophage subtypes ranges from antitumor “M1”-type to protumor “M2”-type macrophages. Tumor-associated macrophages (TAMs) typically display phenotypic features of both M1 and M2, and the population distribution is thought to be dynamic and evolve as the tumor progresses. However, our understanding of how TAMs impact the tumor microenvironment remains limited by the lack of appropriate 3D in vitro models that can capture cell to cell dynamics at high spatial and temporal resolution. Using our recently developed micro-physiological “tumor-on-a-chip” (TOC) device, we present here our findings on the impact of defined macrophage subsets on tumor behavior. The TOC device design contains three adjacent and connected chambers in which both the upper and lower chambers are loaded with tumor cells while the central chamber contains a dynamic, perfused, living microvascular network. Introduction of human pancreatic or colorectal cancer cells together with M1-polorized macrophages significantly inhibited tumor growth and tumor-induced angiogenesis. Protein analysis and antibody-based neutralization studies confirmed that these effects were mediated through production of chemokines CXCL9, CXCL10, and CXCL11. By contrast, M2-macrophages mediated increased tumor cell migration into the vascularized chamber and did not inhibit tumor growth or angiogenesis. In fact, single-cell RNA-sequencing showed that M2 macrophages further segregated endothelial cells into two distinct subsets, corresponding to static cells in vessels versus active cells involved in angiogenesis. The impact of M2 macrophages was mediated mostly by production of MMP7 and ANGPT2. In summary, our data demonstrate the utility of the TOC device to mechanistically probe biological questions in a 3Din vitromicroenvironment.

Insight Box

Macrophages in the tumor microenvironment are key determinants of tumor behavior and clinical outcome. The macrophage subset composition and its functional impact change as tumors progress or during treatment, but adequate models to study this are lacking. We developed a tumor-on-a-chip model of perfused 3D tumor growth to probe the impact of defined macrophage subsets. Our data is consistent with previously described macrophage activity in the tumor microenvironment, and provides potential new molecular targets. Herein, we demonstrate feasibility of probing immuno-oncology questions in a 3Din vitromicroenvironment and at a spatiotemporal resolution.
Minimization of aircraft fuel consumption subjected to arrival time constraint
Authors: Gilani Muhaned , Körpe Durmuş Sinan
Published: May 2020

Purpose

This paper aims to minimize aircraft fuel consumption during the cruise phase when the flight is subjected to a specific time of arrival for different weights and distances.

Design/methodology/approach

The approach adopted herein uses sequential quadratic programming algorithm from MATLAB optimization toolbox, which includes a mathematical model of a jet airliner based on the Base of Aircraft Data as a function evaluator, to find out the impact of meet-time of arrival constraints on fuel consumption. The cruising speeds at predefined segments and the altitude are defined as the design variables.

Findings

The algorithm determines the optimum cruise altitudes and speeds for minimum fuel consumption in the case of no time constraints, also, for different time constraints where the flight time shall be reduced by increasing speed and lowering the altitude in most of the investigated cases.

Practical implications

The algorithm computes the optimum speed and the altitude according to different flight scenarios with the meet-time of arrival constraints for minimum fuel consumption which affects the direct operating cost of the flight. The algorithm might greatly help in decision-making for the meet-time of arrival operations.

Originality/value

Developing an algorithm to optimize the speed and the altitude of an aircraft based on weight and range for minimization of fuel consumption. It is a pioneer study in the literature that deals with the effect of meet-time constraints on fuel consumption.
Family Firms, Alliance Governance and Mutual Knowledge Creation
Authors: Bouncken Ricarda B. , Hughes Mathew , Ratzmann Martin , Cesinger Beate , Pesch Robin
Published: May 2020

For family firms, alliances represent a form of heightened entrepreneurial risk‐taking. However, a dearth of research exists on the implications of forms of alliance governance for family firms. In a study of 939 non‐equity alliances of family and non‐family firms, we analyse how contracts and trust influence mutual knowledge creation. Both contract completeness and trust assist non‐family firms in knowledge creation. However, family firms rely on high levels of trust for the creation of knowledge. Knowledge creation suffers when family firms encounter very complete contracts tied to attempts at high levels of trust. The negative interaction effect is especially strong for non‐owner‐run family firms.
Conscious Proning: An Introduction of a Proning Protocol for Nonintubated, Awake, Hypoxic Emergency Department COVID‐19 Patients
Authors: Jiang Lynn G. , LeBaron Johnathon , Bodnar David , Caputo Nicholas D. , Chang Bernard P. , Chiricolo Gerardo , Flores Stefan , Kenny James , Melville Laura , Sayan Osman R. , Sharma Manish , Shemesh Amos , Suh Edward , Farmer Brenna
Published: May 2020

The novel coronavirus, or COVID‐19, has rapidly become a global pandemic. A major cause of morbidity and mortality due to COVID‐19 has been the worsening hypoxia that, if untreated, can progress to acute respiratory distress syndrome (ARDS) and respiratory failure. Past work has found that intubated patients with ARDS experience physiological benefits to the prone position, because it promotes better matching of pulmonary perfusion to ventilation, improved secretion clearance, and recruitment of dependent areas of the lungs. We created a systemwide multi‐institutional (New York–Presbyterian Hospital enterprise) protocol for placing awake, nonintubated, emergency department patients with suspected or confirmed COVID‐19 in the prone position. In this piece, we describe the background literature and the approach we have taken at our institution as we care for a high burden of COVID‐19 cases with respiratory symptoms.
Factors associated with hypertension and its management among older rural Australians
Authors: Betts Juliana M. , Gao Caroline , Brown David , Ikin Jillian , Maniam Roshan , Stub Dion , Abramson Michael J. , Liew Danny
Published: May 2020

Objectives

Hypertension is a leading risk factor for death and disability. We aimed to estimate the prevalence of hypertension in an older rural Australian cohort and identify predictors of hypertension management.

Design

Analysis of cross‐sectional data collected from participants in a prospective cohort study.

Setting

The Victorian rural towns of Morwell and Sale in 2018‐2019.

Participants

A weighted random sample of 1119 eligible participants from Morwell or Sale, aged ≥55‐90 years for men and ≥60‐90 years for women, was drawn from the Hazelwood Health Study's Adult Survey cohort.

Main outcome measures

Blood pressure, body mass index, left ventricular hypertrophy by electrocardiogram, estimated glomerular filtration rate and glycosylated haemoglobin (HbA1c) were measured. Participants with hypertension were categorised as managed, undermanaged or unmanaged.

Results

Testing undertaken of 498 participants estimated the weighted prevalence of hypertension (defined as blood pressure ≥ 140/90 mm Hg, a self‐reported doctor diagnosis of hypertension or taking antihypertensive medication) to be 79.9% (95% confidence interval: 75.7‐83.4). Of those, 54.5% (49.4‐60.0) had managed hypertension (<140/90 mm Hg), 37.1% (32.3‐42.1) undermanaged hypertension and 8.4% (5.9‐11.9) a new finding of hypertension (unmanaged hypertension). Current employment (relative risk 1.47, 95% confidence interval: 1.06‐2.02) and single marital status (relative risk 1.45, 1.4‐1.84) were associated with under‐ or unmanaged hypertension. Compared with no hypertension, the hypertensive groups were more likely to demonstrate markers of end‐organ damage such as left ventricular hypertrophy and impaired renal function.

Conclusion

Hypertension is a highly prevalent condition among older rural Australians which is suboptimally identified and managed.
Out of hospital management of LVAD patients during COVID‐19 outbreak
Authors: Mariani Silvia , Hanke Jasmin S. , Dogan Günes , Schmitto Jan D.
Published: May 2020

Coronavirus disease 2019 (COVID‐19) is a pandemic touching thousands of people all around the world. Patients supported with left ventricular assist devices (LVADs) are affected by long‐standing cardiovascular diseases and subjected to variations of the normal cardiovascular physiology, thus requiring an even closer monitoring during the COVID‐19 outbreak. Nevertheless, the COVID‐19 pandemic led to a drastic reduction in routine clinical activities and a consequent risk of looser connections between LVAD patients and their referring center. Potential deleterious effects of such a situation can be a delayed recognition of LVAD‐related complications, misdiagnosis of COVID‐19, and impaired social and psychological well‐being for patients and families. As one of the largest LVAD programs worldwide, we designed a sustainable and enforceable telemonitoring algorithm which can be easily adapted to every LVAD center so as to maintain optimal quality of care for LVAD patients during the COVID‐19 pandemic.
Systemic Lupus Erythematosus Activity Affects the Sinusoidal Uptake Transporter OATP1B1 Evaluated by the Pharmacokinetics of Atorvastatin
Authors: Cestari Roberta Natália , de Oliveira Renê Donizeti Ribeiro , de Souza Flávio Falcão Lima , Pippa Leandro Francisco , Nardotto Glauco Henrique Balthazar , Rocha Adriana , Donadi Eduardo Antônio , Lanchote Vera Lucia
Published: May 2020

The present study assessed the effect of systemic lupus erythematosus (SLE) activity, a chronic and inflammatory autoimmune disease, on the sinusoidal uptake transporter OATP1B1 using atorvastatin (ATV) as a probe drug. Fifteen healthy subjects, 13 patients with controlled SLE (SLEDAI 0–4), and 12 patients with uncontrolled SLE (SLEDAI from 6 to 15), all women, were investigated. Apparent total clearance of midazolam (MDZ), a marker of CYP3A4 activity, did not vary among the three investigated groups. The controlled and uncontrolled SLE groups showed higher plasma concentrations of MCP‐1 and TNF‐α, while the uncontrolled SLE group also showed higher plasma concentrations of IL‐10. The uncontrolled SLE group showed higher area under the curve (AUC) for ATV (60.47 (43.76–83.56) vs. 30.56 (22.69–41.15) ng⋅hour/mL) and its inactive metabolite ATV‐lactone (98.74 (74.31–131.20) vs. 49.21 (34.89–69.42) ng⋅hour/mL), and lower apparent total clearance (330.7 (239.30–457.00) vs. 654.5 (486.00–881.4) L/hour) and apparent volume of distribution (2,609 (1,607–4,234) vs. 7,159 (4,904–10,450) L), when compared to the healthy subjects group (geometric mean and 95% confidence interval). The pharmacokinetics of ATV and its metabolites did not differ between the healthy subject group and the patients with controlled SLE group. In conclusion, uncontrolled SLE increased the systemic exposure to both ATV and ATV‐lactone, inferring inhibition of OATP1B1 activity, once in vivo CYP3A4 activity assessed by oral clearance of MDZ was unaltered. The inflammatory state, not the disease itself, was responsible for the changes described in the uncontrolled SLE group as a consequence of inhibition of OATP1B1, because systemic exposure to ATV and its metabolites were not altered in patients with controlled SLE.
Removal of dilated Santorini's duct stones by peroral pancreatoscopy and electrohydraulic lithotripsy through the minor papilla
Authors: Takeshita Kotaro , Asai Satoshi , Fujimoto Naoki
Published: May 2020

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