bluuebunny/crossref_metadata_2025 huggingface dataset:
Medical data collection on UK Military Exercise Saif Sareea 3: the EpiNATO-2 surveillance system
Authors: Chase Stephanie , Kavanagh Williamson M , Smith M
Published: April 2020

Introduction

Epidemiological data from military exercises are important to identify trends in medical presentations and treatment requirements to aid planning for future operations. UK Military exercises use the EpiNATO-2 surveillance system for this purpose, however it has some limitations in the spectrum of data it can collect. An enhanced reporting system titled EpiNATO-2 PLUS was developed and introduced in all LAND (Army) Role 1 Medical Treatment Facilities (MTFs) as part of Exercise Saif Sareea 3 (SS3). It was assessed as part of a Quality Improvement Project for its utility in terms of spectrum and validity of data capture.

Method

Epidemiological data were collected over a 2-month period from medical consultations in Camp Shafa during SS3 by EpiNATO-2 or EpiNATO-2 PLUS. This involved categorisation of symptoms into a coding system which represents a spectrum of clinical presentations, as well as collecting data on the effect of medical issues on personnel productivity. Halfway through the collection period, an EpiNATO-2 PLUS education session and Summary Guide were introduced. Data were audited for the period before and after these introductions.

Results

Of the 1163 consultations conducted in the 2-month period, the use of EpiNATO-2 PLUS captured an additional 169 patient contacts not collected by EpiNATO-2. The provision of a summary guide and teaching session decreased coding errors in the second audit period from 12.9% to 6.8% for EpiNATO-2 and from 19.4% to 6.6% for EpiNATO-2 PLUS, respectively.

Conclusions

The use of EpiNATO-2 PLUS collected a broader spectrum of medical activity in the Role 1 MTF, by capturing an additional 10% of the clinical workload compared with EpiNATO-2. The increase in coding accuracy correlates with the introduction of the education session and EpiNATO-2 PLUS Summary Guide. It is recommended that EpiNATO-2 PLUS is used in future deployments.
YAP1 mediates gastric adenocarcinoma peritoneal metastases that are attenuated by YAP1 inhibition
Authors: Ajani Jaffer A , Xu Yan , Huo Longfei , Wang Ruiping , Li Yuan , Wang Ying , Pizzi Melissa Pool , Scott Ailing , Harada Kazuto , Ma Lang , Yao Xiaodan , Jin Jiankang , Zhao Wei , Dong Xiaochuan , Badgwell Brian D , Shanbhag Namita , Tatlonghari Ghia , Estrella Jeannelyn Santiano , Roy-Chowdhuri Sinchita , Kobayashi Makoto , Vykoukal Jody V , Hanash Samir M , Calin George Adrian , Peng Guang , Lee Ju-Seog , Johnson Randy L , Wang Zhenning , Wang Linghua , Song Shumei
Published: April 2020

Objective

Peritoneal carcinomatosis (PC; malignant ascites or implants) occurs in approximately 45% of advanced gastric adenocarcinoma (GAC) patients and associated with a poor survival. The molecular events leading to PC are unknown. The yes-associated protein 1 (YAP1) oncogene has emerged in many tumour types, but its clinical significance in PC is unclear. Here, we investigated the role of YAP1 in PC and its potential as a therapeutic target.

Methods

Patient-derived PC cells, patient-derived xenograft (PDX) and patient-derived orthotopic (PDO) models were used to study the function of YAP1 in vitro and in vivo. Immunofluorescence and immunohistochemical staining, RNA sequencing (RNA-Seq) and single-cell RNA-Seq (sc-RNA-Seq) were used to elucidate the expression of YAP1 and PC cell heterogeneity. LentiCRISPR/Cas9 knockout of YAP1 and a YAP1 inhibitor were used to dissect its role in PC metastases.

Results

YAP1 was highly upregulated in PC tumour cells, conferred cancer stem cell (CSC) properties and appeared to be a metastatic driver. Dual staining of YAP1/EpCAM and sc-RNA-Seq revealed that PC tumour cells were highly heterogeneous, YAP1highPC cells had CSC-like properties and easily formed PDX/PDO tumours but also formed PC in mice, while genetic knockout YAP1 significantly slowed tumour growth and eliminated PC in PDO model. Additionally, pharmacologic inhibition of YAP1 specifically reduced CSC-like properties and suppressed tumour growth in YAP1highPC cells especially in combination with cytotoxics in vivo PDX model.

Conclusions

YAP1 is essential for PC that is attenuated by YAP1 inhibition. Our data provide a strong rationale to target YAP1 in clinic for GAC patients with PC.
Determinants and prognostic value of echocardiographic first-phase ejection fraction in aortic stenosis
Authors: Bing Rong , Gu Haotian , Chin Calvin , Fang Lingyun , White Audrey , Everett Russell J , Spath Nicholas B , Park Eunsoo , Jenkins William SA , Shah Anoop SV , Mills Nicholas L , Flapan Andrew D , Chambers John B , Newby David E , Chowienczyk Phil , Dweck Marc R
Published: April 2020

Objective

First-phase ejection fraction (EF1) is a novel measure of early left ventricular systolic dysfunction. We investigated determinants of EF1 and its prognostic value in aortic stenosis.

Methods

EF1 was measured retrospectively in participants of an echocardiography/cardiovascular magnetic resonance cohort study which recruited patients with aortic stenosis (peak aortic velocity of ≥2 m/s) between 2012 and 2014. Linear regression models were constructed to examine variables associated with EF1. Cox proportional hazards were used to determine the prognostic power of EF1 for aortic valve replacement (AVR, performed as part of clinical care in accordance with international guidelines) or death.

Results

Total follow-up of the 149 participants (69.8% male, 70 (65–76) years, mean gradient 33 (21–42) mm Hg) was 238 029 person-days. Sixty-seven participants (45%) had a low baseline EF1 (<25%) despite normal ejection fraction (67% (62%–71%)). Patients with low EF1 had more severe aortic stenosis (mean gradient 39 (34–45) mm Hg vs 24 (16–35) mm Hg, p<0.001) and more myocardial fibrosis (indexed extracellular volume (iECV) (24.2 (19.6–28.7) mL/m2vs 20.6 (16.8–24.3) mL/m2, p=0.002; late gadolinium enhancement (LGE) prevalence 52% vs 20%, p<0.001). Zva, iECV and infarct LGE were independent predictors of EF1. EF1 improved post-AVR (n=57 with post-AVR EF1 available, baseline 16 (12–24) vs follow-up 27% (22%–31%); p<0.001). Low baseline EF1 was an independent predictor of AVR/death (HR 5.6, 95% CI 3.4 to 9.4), driven by AVR.

Conclusion

EF1 quantifies early, potentially reversible systolic dysfunction in aortic stenosis, is associated with global afterload and myocardial fibrosis, and is an independent predictor of AVR.
Overcoming hypoxia-induced functional suppression of NK cells
Authors: Solocinski Kristen , Padget Michelle R , Fabian Kellsye P , Wolfson Benjamin , Cecchi Fabiola , Hembrough Todd , Benz Stephen C , Rabizadeh Shahrooz , Soon-Shiong Patrick , Schlom Jeffrey , Hodge James W
Published: April 2020

Background

Natural killer (NK) cells are immune cells capable of killing virally infected cells and tumor cells without the need for antigen stimulation. Tumors, however, can create a suppressive microenvironment that decreases NK function. A feature of many tumors is hypoxia (low oxygen perfusion), which has been previously shown to decrease NK function. A high affinity NK (haNK) cell has been engineered to express a high affinity CD16 receptor as well as internal interleukin (IL)-2 for increased antibody-dependent cellular cytotoxicity (ADCC) and activation, respectively. We sought to investigate the tolerance of NK cells versus haNK cells to hypoxia.

Methods

We exposed healthy donor (HD) NK and X-irradiated haNK cells to normoxia (20% oxygen) as well as hypoxia (0% oxygen) and investigated their ability to kill prostate, breast and lung tumor cell lines after 5 hours. We also used monoclonal antibodies cetuximab (anti-EGFR) or avelumab (antiprogrammed death-ligand 1) to investigate the effects of hypoxia on NK ADCC. Genomic and proteomic analyzes were done to determine the effect of hypoxia on the expression of factors important to NK cell function.

Results

While HD NK cell cytolytic abilities were markedly and significantly impaired under hypoxic conditions, haNK cells maintained killing capacity under hypoxic conditions. NK killing, serial killing and ADCC were maintained under hypoxia in haNK cells. IL-2 has been previously implicated in serial killing and perforin regeneration and thus the endogenous IL-2 produced by haNK cells is likely a driver of the maintained killing capacity of haNK cells under hypoxic conditions. Activation of signal transducer and activator of transcription 3 (STAT3) is not seen in haNKs under hypoxia but is significant in HD NK cells. Pharmaceutical activation of STAT3 in haNKs led to reduced killing, implicating active STAT3 in reduced NK cell function.

Conclusions

In contrast to HD NK cells, haNK cells are resistant to acute hypoxia. The potent cytolytic function of haNK cells was maintained in an environment comparable to what would be encountered in a tumor. The data presented here provide an additional mechanism of action for haNK cells that are currently being evaluated in clinical trials for several tumor types.
CAR T-cell therapy for a relapsed/refractory acute B-cell lymphoblastic lymphoma patient in the context of Li-Fraumeni syndrome
Authors: Chen Liting , Xu Bin , Long Xiaolu , Gu Jia , Lou Yaoyao , Wang Di , Cao Yang , Wang Na , Li Chunrui , Wang Gaoxiang , Wang Ying , Zhu Li , Wang Jin , An Haiyun , Xiao Min , Xiao Yi , Zhou Jianfeng
Published: April 2020

Background

Li-Fraumeni syndrome (LFS) is characterized as an autosomal dominant cancer predisposition disorder caused by germlineTP53gene mutations. Both primary and therapy-related hematopoietic malignancies with LFS are associated with dismal outcomes with standard therapies and even allogenic stem cell transplantation (SCT).

Case presentation

We reported a relapsed/refractory acute B-cell lymphoblastic lymphoma (B-LBL) patient in the context of LFS. He was identified to harbor aTP53c.818G>A (p.R273H) germline mutation, and his family history was significant for rectal carcinoma in his father, an unknown cancer in his sister and acute lymphoblastic leukemia in his brother and one of his sons. The patient received murine monoclonal anti-CD19 and anti-CD22 chimeric antigen receptor (CAR) T-cell “cocktail” therapy and achieved complete remission with negative minimal residual disease (MRD), as assessed by morphology and multiparameter flow cytometry. Fifteen months after murine monoclonal CAR T-cell “cocktail” therapy, the patient’s B-LBL recurred. Fortunately, a round of fully human monoclonal anti-CD22 CAR T-cell therapy was still effective in this patient, and he achieved CR again and continued to be followed. Each time after infusion, the CAR T-cells underwent extremely rapid exponential expansion, which may be due to the disruption ofTP53, a gene that can functionally control cell cycle arrest. Grade 4 and grade 1 cytokine release syndrome occurred after the first and second rounds of CAR T-cell therapy, respectively.

Conclusions

This case provides the first report of the use of CAR T-cell therapy in a hematologic malignancy patient with LFS. As traditional chemotherapy and allogenic SCT are not effective therapy strategies for patients with hematologic malignancies and LFS, CAR T-cell therapy may be an alternate choice.

ChiCTR-OPN-16008526 and ChiCTR1900023922.
Serial CT analysis in idiopathic pulmonary fibrosis: comparison of visual features that determine patient outcome
Authors: Jacob Joseph , Aksman Leon , Mogulkoc Nesrin , Procter Alex J , Gholipour Bahareh , Cross Gary , Barnett Joseph , Brereton Christopher J , Jones Mark G , van Moorsel Coline H , van Es Wouter , van Beek Frouke , Veltkamp Marcel , Desai Sujal R , Judge Eoin , Burd Teresa , Kokosi Maria , Savas Recep , Bayraktaroglu Selen , Altmann Andre , Wells Athol U
Published: April 2020

Aims

Patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotic medication and patients with non-IPF fibrosing lung disease often demonstrate rates of annualised forced vital capacity (FVC) decline within the range of measurement variation (5.0%–9.9%). We examined whether change in visual CT variables could help confirm whether marginal FVC declines represented genuine clinical deterioration rather than measurement noise.

Methods

In two IPF cohorts (cohort 1: n=103, cohort 2: n=108), separate pairs of radiologists scored paired volumetric CTs (acquired between 6 and 24 months from baseline). Change in interstitial lung disease, honeycombing, reticulation, ground-glass opacity extents and traction bronchiectasis severity was evaluated using a 5-point scale, with mortality prediction analysed using univariable and multivariable Cox regression analyses. Both IPF populations were then combined to determine whether change in CT variables could predict mortality in patients with marginal FVC declines.

Results

On univariate analysis, change in all CT variables except ground-glass opacity predicted mortality in both cohorts. On multivariate analysis adjusted for patient age, gender, antifibrotic use and baseline disease severity (diffusing capacity for carbon monoxide), change in traction bronchiectasis severity predicted mortality independent of FVC decline. Change in traction bronchiectasis severity demonstrated good interobserver agreement among both scorer pairs. Across all study patients with marginal FVC declines, change in traction bronchiectasis severity independently predicted mortality and identified more patients with deterioration than change in honeycombing extent.

Conclusions

Change in traction bronchiectasis severity is a measure of disease progression that could be used to help resolve the clinical importance of marginal FVC declines.
Various localized nonlinear wave structures in the (2 + 1)-dimensional KdV system
Authors: Chen Jing , Liu Yaqing , Piao Linhua
Published: April 2020

Korteweg–de-Vries (KdV) equation has many applications such as in the description of shallow water waves and ion-acoustic waves in plasmas. In this paper, we investigate the novel nonlinear wave structures in the [Formula: see text]-dimensional KdV system. Starting from the [Formula: see text]-soliton solution of the [Formula: see text]-dimensional KdV system, some new interaction phenomena of line soliton, breather soliton and lump soliton are found based on the Hirota bilinear method and the long wave limit method. The interaction processes of such solutions are shown graphically to display the novel nonlinear structures in this system. These interesting phenomena in this work could be helpful for understanding certain physical phenomena in nonlinear optics and relevant fields.
Robustness of first-order coherence in duplex networks
Authors: Zhang Jinyan , Sun Weigang , Fan Kai , Guan Junbiao
Published: April 2020

This paper investigates the robustness of first-order coherence characterized by the Laplacian spectrum in duplex networks with varying interlayer linking topologies and node connections of two layers under degree, closeness and eigenvector centrality indicators. The interlayer linking weight and linking rate play an important role in the coherence of duplex networks. The increasing larger linking weight and linking rate make the duplex networks more consensus. In addition, the positively, negatively and randomly correlated linking patterns display diverse consensus behaviors in duplex networks with different interlayer connections. Finally, the linking pattern under the eigenvector centrality has a profound impact on the coherence in the constructed duplex networks. The obtained results of duplex networks may help with a deeper understanding of consensus in multilayer networks.
SHOULDER GIRDLE RESECTION FOR BONE TUMORS, A MODIFICATION IN THE SURGICAL TECHNIQUES AND INTRODUCTION OF A NEW CLASSIFICATION SYSTEM
Authors: Shehadeh Ahmed , Ja’far Ahmad F. , Hamad Anas
Published: April 2020

Background: Surgical techniques for resection of tumors at proximal humerus and scapula has been described in literature along with different classification systems, however, these techniques have not been revised for a while and the classification systems which are currently in use neither respect the difference between bone and soft tissue tumors nor the anatomical location humeral vs scapular. Material and Methods: The author operated on 32 patients with shoulder girdle tumors, all are bone tumors, Ewings sarcoma ([Formula: see text]), Osteosarcoma ([Formula: see text]), Metastatic tumors ([Formula: see text]), GCT ([Formula: see text]), Chondrosarcoma ([Formula: see text]). We assigned two separate classifications to humerus and scapula resection, since surgical approaches, techniques, and reconstruction options are totally different for the both sites. Resection of the humerus is classified into: Type I to Type IV, A: is added to the type when the majority of Deltoid is preserved, and B: when it is sacrificed. And we classify the scapula resection into: Type I to Type III, A: is added to the type when the majority of Deltoid is preserved, and B: when it is sacrificed. In extra articular humerus resection, we found that sacrificing the acromion and coracoid process is not necessary as part of routine resection. Preservation of these structures can improve the cosmetic appearance of the shoulder with at least equal functional outcome. Endoprosthesis was used in 26 patients for reconstruction, osteoarticular allograft was used in 2 patients, and Tichoff Lindberg technique for 4 patients. Results: At 30 month mean follow up period, 2 patients developed local recurrence (osteosarcoma [Formula: see text], Ewing Sarcoma [Formula: see text]), 2 patients had wound infection, and one patient developed stem loosening. The average MSTS functional score for all patients was 83%. Conclusion: The modification of surgical techniques saved structures which were unnecessarily resected, and kept the integrity of muscles and their attachments which were sacrificed in previously described techniques. This might lead to fewer restrictions during the rehabilitation process and resulted in preservation of the shoulder contour. The new classification system is realistic, separates the humeral resection from the scapular one, easy to be recalled and applicable to all patients.
Christopher Dobson, 1949–2019: Mentor, Friend, Scientist Extraordinaire
Authors: Robinson Carol V.
Published: April 2020

It is impossible to do justice in one review article to a researcher of the stature of Christopher Dobson. His career spanned almost five decades, resulting in more than 870 publications and a legacy that will continue to influence the lives of many for decades to come. In this review, I have attempted to capture Chris's major contributions: his early work, dedicated to understanding protein-folding mechanisms; his collaborative work with physicists to understand the process of protein aggregation; and finally, his later career in which he developed strategies to prevent misfolding. However, it is not only this body of work but also the man himself who inspired an entire generation of scientists through his patience, ability to mentor, and innate generosity. These qualities remain a hallmark of the way in which he conducted his research—research that will leave a lasting imprint on science.
Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns
Authors: Galli Stephen J. , Gaudenzio Nicolas , Tsai Mindy
Published: April 2020

Mast cells have existed long before the development of adaptive immunity, although they have been given different names. Thus, in the marine urochordate Styela plicata, they have been designated as test cells. However, based on their morphological characteristics (including prominent cytoplasmic granules) and mediator content (including heparin, histamine, and neutral proteases), test cells are thought to represent members of the lineage known in vertebrates as mast cells. So this lineage presumably had important functions that preceded the development of antibodies, including IgE. Yet mast cells are best known, in humans, as key sources of mediators responsible for acute allergic reactions, notably including anaphylaxis, a severe and potentially fatal IgE-dependent immediate hypersensitivity reaction to apparently harmless antigens, including many found in foods and medicines. In this review, we briefly describe the origins of tissue mast cells and outline evidence that these cells can have beneficial as well as detrimental functions, both innately and as participants in adaptive immune responses. We also discuss aspects of mast cell heterogeneity and comment on how the plasticity of this lineage may provide insight into its roles in health and disease. Finally, we consider some currently open questions that are yet unresolved.
Vaccines and Broadly Neutralizing Antibodies for HIV-1 Prevention
Authors: Stephenson Kathryn E. , Wagh Kshitij , Korber Bette , Barouch Dan H.
Published: April 2020

Development of improved approaches for HIV-1 prevention will likely be required for a durable end to the global AIDS pandemic. Recent advances in preclinical studies and early phase clinical trials offer renewed promise for immunologic strategies for blocking acquisition of HIV-1 infection. Clinical trials are currently underway to evaluate the efficacy of two vaccine candidates and a broadly neutralizing antibody (bNAb) to prevent HIV-1 infection in humans. However, the vast diversity of HIV-1 is a major challenge for both active and passive immunization. Here we review current immunologic strategies for HIV-1 prevention, with a focus on current and next-generation vaccines and bNAbs.
Innate Lymphocyte Mechanisms in Skin Diseases
Authors: Chen Yi-Ling , Hardman Clare S. , Yadava Koshika , Ogg Graham
Published: April 2020

Innate lymphocyte populations are emerging as key effectors in tissue homeostasis, microbial defense, and inflammatory skin disease. The cells are evolutionarily ancient and carry conserved principles of function, which can be achieved through shared or unique specific mechanisms. Recent technological and treatment advances have provided insight into heterogeneity within and between individuals and species. Similar pathways can extend through to adaptive lymphocytes, which softens the margins with innate lymphocyte populations and allows investigation of nonredundant pathways of immunity and inflammation that might be amenable to therapeutic intervention. Here, we review advances in understanding of innate lymphocyte biology with a focus on skin disease and the roles of commensal and pathogen responses and tissue homeostasis.
Robotic Partial Nephrectomy with Indocyanine Green Fluorescence Navigation
Authors: Gadus Lukas , Kocarek Jiri , Chmelik Frantisek , Matejkova Marketa , Heracek Jiri
Published: April 2020

Partial nephrectomy (PN) is a recommended type of treatment of localised renal tumors. Real-time intraoperative imaging technique, such as fluorescence imaging with indocyanine green (ICG) administration helps to improve intraoperative and postoperative outcomes in patients who underwent PN. Our work presents results of patients who underwent robotic PN with ICG navigation. A total of 37 patients underwent robotic PN with application of ICG between April 2015 and May 2019. A total amount of 5 mg of ICG was applied intravenously, and then robotic PN was performed with fluorescent imaging. ICG was used by the surgeon’s decision according to unfavourable anatomical properties of tumor or to high R.E.N.A.L. nephrometry score. An exact border between perfused and nonperfused tissue was detected, and exact tumor’s branch of the renal artery was clamped. Robotic PN with ICG-fluorescence imaging navigation was performed in 37 cases with a preoperative average diameter of tumor of 31 mm. The mean surgery time was 133 minutes, and the mean estimated blood loss was 190 mL. Arterial clamping was performed in 35 cases. The mean duration of warm ischemia was 14 minutes. Application of ICG enabled specific tumor-supplying vessel clamping in 25 cases. Two complications of grade II according to the Clavien-Dindo classification occurred intraoperatively, and one complication of grade III was observed. Renal function changes showed favourable results for the cases with superselective clamping. Finally, an administration of ICG eases superselective clamping of tumor-specific branch of renal artery and helps to preserve normal renal function with acceptable oncological results.
Adenocarcinoma with Neuroendocrine Differentiation of the Colon Accompanying Osteoclast-Like Giant Cells
Authors: Tachibana Mitsuhiro , Isono Tadahiro , Tsutsumi Yutaka
Published: April 2020

Introduction. Neuroendocrine differentiation in colorectal cancer is reportedly associated with poorer grade of tumor differentiation, nodal and distant metastasis, and other unfavorable features, contributing to a worse clinical outcome. Colorectal cancer with osteoclast-like giant cells (OGCs) is extremely rare. Case Presentation. An 86-year-old woman was diagnosed as double cancer of the transverse and sigmoid colon. Both tumors were simultaneously removed. The transverse colon cancer directly invaded the area of the right gastroepiploic vessels and spread to the nodes and histologically consisted of both the tubuloglandular and solid components. CD8/granzyme B-positive tumor-infiltrating lymphocytes and CD163/CD68-positive macrophages, frequently forming OGCs, were observed particularly at the invasion front. The carcinoma cells were labeled focally for synaptophysin and diffusely for the DR locus of the human leukocyte antigen and programmed death-ligand 1 (PD-L1). Deficient expression of DNA mismatch repair (dMMR) proteins was immunohistochemically confirmed. The patient died 16 months after surgery. Conclusion. This is the first report of colonic adenocarcinoma with neuroendocrine differentiation accompanying OGCs. Histopathologic factors of the poor prognosis in the present case included (a) the presence of more than 2% cells with neuroendocrine differentiation, (b) infiltration of CD163/CD68-positive OGCs at the invasion front, (c) deficiency of dMMR proteins, and (d) PD-L1 expression.
Effect of Electroacupuncture in Mice with Dextran Sulfate Sodium‐Induced Colitis and the Influence of Gut Microbiota
Authors: Liu Geng-Hao , Liu Hsuan-Miao , Chen Yu-Sheng , Lee Tzung-Yan
Published: April 2020

Background. The relationship between inflammatory bowel disease and gut microbiota is inextricable. Electroacupuncture (EA) can alleviate acute experimental colitis, but the performance of intestinal microorganisms and the mechanism are still not fully understood. We investigated the relationship between the EA and gut microbes and clarified the role of tight junction and adiponectin in the anti‐inflammatory effect of EA. Methods. Male C57BL/6 mice were randomized into three groups: normal control, dextran sulfate sodium‐ (DSS‐) induced ulcerative colitis (DSS), and DSS with EA ST36 (DSS + EA). Mice body weight, DAI score, colon length, and histological score were evaluated for colitis severity. Colonic inflammation and tight junctions were demonstrated by the immunohistochemical (IHC) method. Systemic responses were confirmed by plasma cytokines and adiponectin with multiplex immunoassays. Gut microbiome profiling was conducted by 16S rRNA gene sequencing. Results. EA had benefit in relieving both macroscopic and microscopic colonic inflammation. It can reduce disease activity, maintain colon length, and ameliorate histological inflammatory reaction. In IHC stain, EA decreased CD11b, F4/80, TLR4, and MyD88 and preserved claudin‐1 and ZO‐1 expression. Compared with the control group, the DSS group showed elevated levels of CRP, IFN‐γ, TNF‐α, and IL‐6, but decreased adiponectin. These changes were reversed by EA, accompanied by modulation of the overall structure of gut microbiota. Conclusion. Our findings suggest that EA exerts its therapeutic effect by TLR4 signaling via the MyD88‐dependent pathway. EA could increase adiponectin, maintain mucosal tight junctions, and modulate gut microbiota.
Crosstalk of MicroRNAs and Oxidative Stress in the Pathogenesis of Cancer
Authors: Lu Can , Zhou Danting , Wang Qiang , Liu Wenliang , Yu Fenglei , Wu Fang , Chen Chen
Published: April 2020

Oxidative stress refers to an imbalance between reactive oxygen species (ROS) generation and body’s capability to detoxify the reactive mediators or to fix the relating damage. MicroRNAs are considered to be important mediators that play essential roles in the regulation of diverse aspects of carcinogenesis. Growing studies have demonstrated that the ROS can regulate microRNA biogenesis and expression mainly through modulating biogenesis course, transcription factors, and epigenetic changes. On the other hand, microRNAs may in turn modulate the redox signaling pathways, altering their integrity, stability, and functionality, thus contributing to the pathogenesis of multiple diseases. Both ROS and microRNAs have been identified to be important regulators and potential therapeutic targets in cancers. However, the information about the interplay between oxidative stress and microRNA regulation is still limited. The present review is aimed at summarizing the current understanding of molecular crosstalk between microRNAs and the generation of ROS in the pathogenesis of cancer.
Effects of Compressive and Tensile Strain on Macrophages during Simulated Orthodontic Tooth Movement
Authors: Schröder Agnes , Käppler Paul , Nazet Ute , Jantsch Jonathan , Proff Peter , Cieplik Fabian , Deschner James , Kirschneck Christian
Published: April 2020

During orthodontic tooth movement (OTM) to therapeutically correct the position of misaligned teeth, thus improving oral health and quality of life, fibroblasts, macrophages, and other immune cells within the periodontal ligament (PDL), which connects a tooth to its surrounding bone, are exposed to compressive and tensile strain. While it is known that PDL fibroblasts are critically involved in the biological regulation of OTM by a mechanotransductively triggered release of cytokines, it is unclear whether macrophages also react to pressure and tension in a similar manner thus impacting on or mediating OTM. RAW264.7 macrophages were seeded onto conventional 6-well cell culture plates for pressure or on Bioflex plates for tension assays and preincubated for 24 h. Forin vitrosimulation of physiological orthodontic compressive or tensile strain for 2 h, 4 h, 24 h, and 48 h, glass discs (2 g/cm2) were placed or adherent macrophages isotropically stretched for 16%, respectively. We determined cell number, cytotoxicity, and gene/protein expression ofVegf-a/VEGF-A (macrophage-mediated angiogenesis),Mmp-8/9(extracellular matrix reorganization), andCox-2/PG-E2,Il-6/IL-6, andTnf-α/TNF-α(proinflammatory mediators) by RT-qPCR and ELISA. Compressive but not tensile strain resulted in a significant reduction in cell number after only 2 h.Mmp-8andMmp-9expression was significantly enhanced within 24 h of compressive and in part tensile strain. Significantly increasedVegf-a/VEGF-A expression was detected within 4 h of pressure, but not during application of tensile strain. Expression of proinflammatory mediatorsCox-2/PG-E2,Il-6/IL-6, andTnf-α/TNF-αwas significantly increased as early as 2-4 h after application of compressive or tensile strain. Our results indicate that macrophages respond early on to compressive and tensile strain occurring during OTM with an enhanced gene expression of proinflammatory cytokines, which could affect PDL fibroblasts, osteoblasts, and immune cells triggering or enhancing the biological mechanisms and osteoclastogenesis underlying OTM.
A Study of the Relationship between the Polymorphism and Mutation of rs682429 and rs3781590 in the LRP5 Gene and Bone Metabolism in Postmenopausal Type 2 Diabetic Women in Xinjiang
Authors: Li Jun , Li SiYuan , Zhao HuiRong , Li JiaJia , Wang Shuang , Shi YanQiu
Published: April 2020

Objective. To explore the expression of the polymorphism and mutation of rs682429 and rs3781590 in the low-density lipoprotein receptor-related protein 5 (LRP5) genotype and to analyse the relationship of bone mineral density (BMD) and bone metabolism markers in postmenopausal women with type-2 diabetes mellitus (T2DM) in Xinjiang, China, to provide a basis for prevention and treatment of the disease. Methods. A total of 136 postmenopausal women were included in the study. According to the results of an oral glucose tolerance test (OGTT) and dual-energy X-ray (DEXA) determination of BMD, the study subjects were divided into 4 groups: group A: normal OGTT+normal bone mass group; group B: normal OGTT+osteoporotic (OP) group; group C: T2DM+normal bone mass group; group D: T2DM+osteoporotic (OP) group. Calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and clinical biochemical data were determined; haemoglobin A1c (HbA1c) was measured by HPLC; BMD of the femoral neck, hip, and lumbar spine (L1-4) was measured by dual-energy X-ray (DEXA); and the rs682429 and rs3781590 polymorphisms of the LRP5 gene were detected by time-of-flight mass spectrometry (TOF MS). Results. (1) The rs682429 polymorphism of the LRP5 genotype distribution was statistically significant (P<0.05) in group B compared with group A. (2) The triglycerides (TG) of women with the CT/TT genotype (mutant type) were higher than those of women with the CC genotype (wild type) (2.37±1.30 vs. 1.52±0.83, P<0.05) at the rs3781590 site of the LRP5 gene in group D. (3) Multiple linear regression analysis showed that TG (β=0.034, P<0.05) and body mass index (BMI) (β=0.013, P<0.05) were the influencing factors of BMD (L1-4) in T2DM patients. TG (β=0.022, P<0.05), BMI (β=0.009, P<0.05), and duration of menopause (β=0.005, P<0.05) were the influencing factors of BMD (hip). Conclusion. (1) The rs682429 polymorphism site in the LRP5 gene may be involved in bone metabolism in postmenopausal women from Xinjiang. (2) The rs3781590 mutation in the LRP5 gene from these subjects may be involved in lipid metabolism. (3) Among postmenopausal women with type 2 diabetes mellitus and bone mass abnormality in the Xinjiang Shihezi area, high BMI and TG are protective factors against increased BMD. Duration of menopause is a risk factor for increased BMD.
Effects of Rhythmic Sensory Stimulation on Ehlers–Danlos Syndrome: A Pilot Study
Authors: Vuong Veronica , Mosabbir Abdullah , Paneduro Denise , Picard Larry , Faghfoury Hanna , Evans Michael , Gordon Allan , Bartel Lee
Published: April 2020

Ehlers–Danlos syndrome (EDS) is a connective tissue disorder characterized by joint hypermobility and skin extensibility and is often accompanied by chronic pain. Rhythmic sensory stimulation (RSS) can be defined as the stimulation of the senses in a periodic manner within a range of low frequencies. Music plus sound delivered through a vibroacoustic device is a form of RSS and has demonstrated utility in managing pain. In this current study, we conducted an open-label pilot study of 15 patients with hypermobile EDS using RSS as the intervention. Posttreatment improvements were seen in 11 of the 15 patients (73%), whereas 3 of the 15 patients (20%) experienced worse outcomes. Of the 14 patients that completed the experiment, 6 participants (43%) were classified as “responders” to the device while 8 participants (57%) were classified as “nonresponders.” Responders demonstrated significant improvements in pain interference (51.5 ± 16 preintervention vs. 43.5 ± 16.4 postintervention BPI score) and depression symptoms (34.0 ± 15.9 preintervention vs. 26.8 ± 12.1 postintervention CESD score). Poststudy interviews confirm the improvements of pain interference, mood, and bowel symptoms. Furthermore, analysis of medical conditions within the responder group indicates that the presence of depression, anxiety, irritable bowel syndrome, and fibromyalgia may indicate a greater likelihood for patients to benefit with vibroacoustic applications. These results indicate a possible potential for RSS, delivered using a vibroacoustic device, in managing pain-related symptoms. Further research is necessary to elucidate the exact mechanism behind the physiological benefits of RSS.
Analysis of SIRT1 Expression in Plasma and in an In Vitro Model of Preeclampsia
Authors: Viana-Mattioli Sarah , Nunes Priscila , Cavalli Ricardo , Sandrim Valeria
Published: April 2020

Preeclampsia (PE) is a pregnancy-specific disorder that affects 3–8% expecting mothers worldwide being one of the main causes of maternal and fetal morbidity and mortality. The search for altered circulating molecules in PE is an important target to better understand the pathophysiology of this disease. Therefore, we evaluated Sirtuin-1 (SIRT1) concentration in plasma from healthy pregnant (HP) women, gestational hypertensive women (GH), and preeclampsia women (PE) via enzyme-linked immunosorbent assay (ELISA). We also measured intracellular SIRT1 in HUVECs incubated with plasma from PE patients compared to HP and GH via Western Blot Assay. Statistical differences were considered when p<0.05. SIRT1 was downregulated in PE compared to HP and GH, both in plasma and in in vitro assay. Similarly, SIRT1 was also reduced in pregnant women who subsequently developed PE (case) compared to women who had healthy pregnancies (control). This reduction may be indicative of possible underlying pathophysiology mechanisms in PE.
Contract Design for Cloud Logistics (CL) Based on Blockchain Technology (BT)
Authors: Xu Lan , Tu Paul , Tang Qian
Published: April 2020

Purpose. This paper aims to design the contract and present the profit distribution mechanism for CL platform, so as to realize the intelligent and automatic operation of the artificial intelligent- (AI-) based CL platform. Design/Methodology. A smart contract based on BT is designed for the AI-based CL platform. Profit distribution mechanism based on the Nash bargaining model for the CL platform is also put forward to coordinate different participators’ benefit relationship in CL. Findings. The AI-based CL platform and the proposed smart contract based on BT map the scenario which may be influenced by human factors and involve trust issues onto execution of codes. Practical Implications. The study will help CL practitioners in establishing effective profit mechanism and designing contracts on the platform, thus facilitating its sustainable operation. Originality/Value. The AI-based CL platform with BT smart contract can be totally free of human intervention, and hence, the problems of trust during CL platform’s operation are solved.
Fatal Methanol Poisoning Caused by Drinking Adulterated Locally Distilled Alcohol: Wakiso District, Uganda, June 2017
Authors: Doreen Birungi , Eyu Patricia , Okethwangu Denis , Biribawa Claire , Kizito Susan , Nakanwagi Miriam , Nguna Joyce , Nkonwa Innocent H. , Opio Denis N. , Aceng Freda L. , Alitubeera Phoebe H. , Kadobera Daniel , Kwesiga Benon , Bulage Lilian , Ario Alex R. , Zhu Bao-Ping
Published: April 2020

Background. Methanol, an industrial solvent, can cause illness and death if ingested. In June 2017, the Uganda Ministry of Health was notified of a cluster of deaths which occurred after drinking alcohol. We investigated to determine the cause of outbreak, identify risk factors, and recommend evidence-based control measures. Methods. We defined a probable case as acute loss of eyesight and ≥1 of the following symptoms: profuse sweating, vomiting, dizziness, or loss of consciousness in a resident of either Nabweru or Nangabo Subcounty from 1 to 30 June 2017. In a case-control study, we compared exposures of case-patients and controls selected among asymptomatic neighbors who drank alcohol and matched by age and sex. We collected alcohol samples from implicated bars and wholesaler X for testing. Results. We identified 15 cases; 12 (80%) died. Among case-patients, 12 (80%) were men; the median age was 43 (range: 23–66) years. Thirteen (87%) of 15 case-patients and 15 (25%) of 60 controls last drank a locally distilled alcohol at one of the three bars supplied by wholesaler X (ORM-H = 15; 95% CI: 2.3–106). We found that alcohol sellers sometimes added methanol to drinking alcohol to increase their profit margin. Among the 10 alcohol samples from wholesaler X, the mean methanol content (1200 mg/L, range: 77–2711 mg/L) was 24 times higher than the safe level. Conclusion. This outbreak was caused by drinking a locally distilled alcohol adulterated with methanol from wholesaler X. We recommended enforcing existing laws governing alcohol manufacture and sale. We recommended timely intravenous administration of ethanol to methanol poisoning victims.
Resveratrol Attenuates High Glucose‐Induced Vascular Endothelial Cell Injury by Activating the E2F3 Pathway
Authors: Ding Xiaolian , Yao Wei , Zhu Jie , Mu Kaida , Zhang Jing , Zhang Jin-an
Published: April 2020

Type 2 diabetes mellitus (T2DM) is the most common metabolic disease. High glucose‐induced macrovascular disease and microangiopathy are major complications of diabetes. E2F3, a member of the E2F transcription factor family, is closely related to cardiovascular diseases. Resveratrol, a nonflavonoid polyphenolic compound widely found in plants, has been shown to have cardiovascular protection. However, there are few studies on whether resveratrol can effectively treat diabetic angiopathy, and the specific mechanism involved needs further study. This study investigated whether E2F3 transcription factors are involved in the process of vascular endothelial injury induced by high glucose and observed its effects on the proliferation of vascular endothelial cells. Then, it analyzed whether resveratrol can inhibit high glucose‐induced vascular endothelial cell injury by regulating the E2F3 pathway. We demonstrated that the expression level of the E2F3 transcription factor was significantly inhibited in high glucose state. Resveratrol inhibited high glucose‐induced vascular endothelial cell injury by upregulating the E2F3 pathway. High glucose can induce vascular endothelial injury by inhibiting E2F3 gene expression, while resveratrol can inhibit high glucose‐induced vascular endothelial injury by activating the E2F3 pathway.
Microwave Synthesis of MCM-41 and Its Application in CO2 Absorption by Nanofluids
Authors: Cheng Shang-Yuan , Liu You-Zhi , Qi Gui-Sheng
Published: April 2020

Microwave synthesis method is a green chemical process with mild reaction conditions, fast reaction, and low energy consumption. In this work, an order mesoporous silica material MCM-41 was synthesized by microwave technology. Functionalized MCM-41 was prepared by wet impregnation with polyethyleneimine (PEI). XRD, SEM, TEM, DLS, N2 adsorption-desorption, FTIR, and TG were used to characterize the physicochemical properties of samples. Furthermore, CO2 absorption performance in water in the presence of uncalcined MCM-41 and PEI-MCM-41 nanoparticles was evaluated. In addition, the mechanisms of enhanced absorption were also elaborated. The experimental results indicated that the optimum conditions for preparation of MCM-41 were the microwave time of 15 min, microwave temperature of 100°C, and microwave power of 200 W. Under this condition, MCM-41 with narrow particle size distribution, average diameter of 50 nm, and SBET of 1210.3 m2g-1 was obtained. The enhancement effect of PEI-MCM-41 nanoparticles was more obvious than that of uncalcined MCM-41. PEI-MCM-41 as a promoter not only increased the CO2 diffusion rate but also enhanced the adsorption capacity due to the fact that it owns more active sites that may react with CO2. The CO2 absorption improvement of PEI-MCM-41 (0.1 wt%)/H2O was 25.35% higher than that of water.
Pulmonary Alveolar Microlithiasis: An Isolated Case in a Hispanic Male
Authors: Menon Preethi Dileep , Hackman Sarah
Published: April 2020

Pulmonary alveolar microlithiasis (PAM) is an uncommon hereditary lung disease characterized by widespread deposition of calcium phosphate microliths within the alveolar spaces. It is considered an autosomal recessive disease with a mutation in a gene encoding a sodium phosphate cotransporter. The imaging findings in the early phase of disease can be mistaken for miliary tuberculosis or sarcoidosis. However, the classic radiologic findings in the later phases of disease show numerous opacities causing a “snowstorm” appearance to the lungs that corresponds with widespread deposition of microliths throughout the lung parenchyma. Although the disease often progresses over a slow time course, there are no effective therapies, and bilateral lung transplantation is recommended when there are increasing oxygen requirements or evidence of pulmonary hypertension.
The Efficacy and Safety of Elobixibat for the Elderly with Chronic Constipation: A Multicenter Retrospective Cohort Study
Authors: Tomie Akira , Yoshida Naohisa , Kugai Munehiro , Hirose Ryohei , Dohi Osamu , Inoue Ken , Okuda Kotaro , Motoyoshi Takayuki , Fukumoto Kohei , Inagaki Yoshikazu , Yoriki Hiroyuki , Inada Yutaka , Okuda Takashi , Hasegawa Daisuke , Ogiso Kiyoshi , Murakami Takaaki , Soga Koichi , Rani Rafiz Abdul , Yoshida Norimasa , Itoh Yoshito
Published: April 2020

Backgrounds and Aims. Elobixibat is a bile acid transporter inhibitor indicated for constipation. Previous studies were performed mainly for the nonelderly and were biased to female. We analyzed the efficacy of elobixibat also for the elderly and male. Materials and Methods. This was a multicenter retrospective cohort study. The subjects were patients aged ≥20 years treated for chronic constipation from May 2018 to November 2019 at 12 related institutions. Patients were divided into ≤74 years and ≥75 years old. Elobixibat at 10 mg/day was prescribed for two weeks. We then analyzed the discontinuation due to ineffectiveness, change of spontaneous bowel movements (SBM), stool consistency, the time until the first SBM, adverse events, and effect-related factors. Results. There were 140 cases (61 males) evaluated, with an average age of 72.1±13.6 years (≤74 years: 71 cases; ≥75 years: 69 cases). The discontinuation rate was 7.9%. The SBM (times/week) increased from 2.86 to 6.08 (p<0.001). The overall SBM improvement rate was 74.0% (≤74 years: 78.2% vs. ≥75 years: 68.9%, p=0.31; male: 75.0% vs. female: 73.3%, p=0.78). The overall improvement rate of stool consistency was 59.6% (≤74 years: 62.9%, ≥75 years: 56.1%, p=0.42). The time until the first SBM (hours) for those ≤74 years and ≥75 years was 17.2±14.3 and 11.2±8.4 (p=0.04). Adverse event rates for those ≤74 years and ≥75 years were 28.2% and 10.1% (p<0.01). There were no significant effect-related factors for gender, age, and use of laxatives. Conclusions. Short-period elobixibat is shown to be effective also for the elderly and male.
Cancer Exacerbates Chemotherapy-Induced Sensory Neuropathy
Authors: Housley Stephen N. , Nardelli Paul , Carrasco Dario I. , Rotterman Travis M. , Pfahl Emily , Matyunina Lilya V. , McDonald John F. , Cope Timothy C.
Published: April 2020

For the constellation of neurologic disorders known as chemotherapy-induced peripheral neuropathy, mechanistic understanding and treatment remain deficient. Here, we present the first evidence that chronic sensory neuropathy depends on nonlinear interactions between cancer and chemotherapy. Global transcriptional profiling of dorsal root ganglia revealed differential expression, notably in regulators of neuronal excitability, metabolism, and inflammatory responses, all of which were unpredictable from effects observed with either chemotherapy or cancer alone. Systemic interactions between cancer and chemotherapy also determined the extent of deficits in sensory encoding and ion channel protein expression by single mechanosensory neurons, with the potassium ion channel Kv3.3 emerging as one potential contributor to sensory neuron dysfunction. Validated measures of sensorimotor behavior in awake, behaving animals revealed dysfunction after chronic chemotherapy treatment was exacerbated by cancer. Notably, errors in precise forelimb placement emerged as a novel behavioral deficit unpredicted by our previous study of chemotherapy alone. These original findings identify novel contributors to peripheral neuropathy and emphasize the fundamental dependence of neuropathy on the systemic interaction between chemotherapy and cancer.

Significance:

These findings highlight the need to account for pathobiological interactions between cancer and chemotherapy as a major contributor to neuropathy and will have significant and immediate impact on future investigations in this field.