bluuebunny/crossref_metadata_2025 huggingface dataset:
A Behavioral Health Program for Alcohol Use Disorder, Substance Abuse, and Depression in Chronic Liver Disease
Authors: Verma Manisha , Horrow Jay , Navarro Victor
Published: March 2019

Alcohol use disorder, substance abuse, and depression are illnesses that deteriorate the quality of life (QOL) of patients with chronic liver disease (CLD). Screening and behavioral health programs integrated into routine practice can mitigate the deleterious effects of such illnesses but have not been adopted in hepatology practices. We implemented a behavioral health program based on the Screening, Brief Intervention, and Referral to Treatment (SBIRT) model and assessed its acceptability and effectiveness in improving QOL. This was a quality improvement study. Patients with CLD and a scheduled outpatient visit in the hepatology clinic were screened while waiting for their appointment. All patients who screened positive for any of the three illnesses were offered a brief intervention (BI) at the point of care and at 3 months by a trained social worker. The BI used the principles of motivational interviewing and cognitive behavioral therapy. Severity of illness was assessed at baseline, 3 months, and 6 months. Participants completed an acceptability survey at 6 months. We screened 303 patients; 61.7% were positive for any of the three illnesses assessed. Among the positive patients, depression was most common (48.4%), alcohol and substance abuse were each 26%. For the 95 patients who underwent BI, QOL improved from baseline to 3 and 6 months (P < 0.001) and patients with depression improved the most. Depression was the only independent predictor of change in QOL over time. Of the enrolled patients, 82% agreed BIs improved their overall care and 87% indicated a desire to continue with the behavioral program. Conclusion: An outpatient behavioral health program based on the SBIRT model is acceptable to patients with CLD and may help improve QOL over time.
Status of public–private partnership recognition and willingness to pay for private health care in China
Authors: Wang Yongfei , Zhang Liang
Published: March 2019

Objectives

The Chinese government has been increasingly engaging and interacting with the private sectors to initiate public–private partnerships (PPPs) to enhance the capacity of the health care system. Thus, the availability of private health services and copays are increasing. However, Chinese residents appear to be more accustomed to public health care because it has long been the dominant health service provider in China. Therefore, learning how the Chinese recognize PPPs, whether they would like to use private health services and how much they are willing to pay out of pocket are important for policymakers.

Methods

A bibliographical search was performed through PubMed in Medline, the Chinese National Knowledge Infrastructure and key government websites using a combination of keywords from seminal papers on PPPs and then sequentially added “willingness to pay (WTP), health, and private.” The papers selected were closely related to PPPs and WTP for health care in China, and then, over 100 peer‐reviewed literature, opinion, or commentary papers and postgraduate theses on the particular topics were carefully reviewed.

Results

Out of 139 papers closely related to WTP for private health care, 37 were extensively reviewed and substantially analyzed. The results corroborate that Chinese residents are generally willing to pay for high‐risk disease screening, improved therapies, and health insurance, although the WTP intentions and the amounts they are willing to pay are different among distinct populations for the various types of health services. The results also present conditions that the responders are not explicitly willing to pay for or are willing to pay additional fees for their health promotion. Education level, family per capita income, self‐reported health status, and dwelling districts (such as urban or rural residents) are the main factors that affect cost‐sharing intention.

Conclusions

PPPs are increasingly recognized as an effective means to mobilize resources in the private sector to relieve the pressure/burden placed on the public system during medical reform in China. Responders in China are generally willing to pay reasonable fees out of pocket for primary health care services or for improved therapies; however, cost‐sharing intentions are affected by multiple factors. Health‐related policymakers should learn the general health concerns/demands of the residents and their WTP status to perfect the design of PPPs for the benefit of the majority population in China.
Natural history of human papillomavirus and vaccinations in men: A literature review
Authors: Lieblong Benjamin J. , Montgomery Brooke E. E. , Su L. Joseph , Nakagawa Mayumi
Published: March 2019

Background and aims

Infection with high‐risk (HR) genotypes of the human papillomavirus (HPV) is necessary for and causative of almost all cervical cancers and their precursor condition, cervical intraepithelial neoplasia. These conditions have been sharply reduced by cervical cytology screening, and a further decrease is expected because of the recent introduction of prophylactic HPV vaccinations. While significant attention has been given to gynecologic HPV disease, men can be affected by HPV‐related cancers of the anus, penis, and oropharynx. This literature review aims to address disparities in HPV‐related disease in men, and certain HR male subpopulations, compared with women.

Discussion

Overall, immunocompetent men are far less likely than women to develop anogenital HPV‐related cancers, despite harboring HR HPV infections at anogenital sites. On the other hand, men who have sex with men and men living with human immunodeficiency virus infection are at considerably higher risk of HPV‐related disease. Historic rates of prophylactic HPV vaccination in males have trailed those of females due to numerous multilevel factors, although, in recent years, this sex gap in vaccination coverage has been closing. In the absence of routine HPV screening in males, therapeutic vaccinations have emerged as a potential treatment modality for preinvasive neoplasia and are in various phases of clinical testing.

Conclusion

Successful reductions in HPV disease morbidity at the population level must acknowledge and target HPV infections in men.
Spatial controls on the distribution and dynamics of a marginal snowpack in the Australian Alps
Authors: Bilish Shane P. , Callow J. Nikolaus , McGrath Gavan S. , McGowan Hamish A.
Published: March 2019

Seasonal snowpacks in marginal snow environments are typically warm and nearly isothermal, exhibiting high inter‐ and intra‐annual variability. Measurements of snow depth and snow water equivalent were made across a small subalpine catchment in the Australian Alps over two snow seasons in order to investigate the extent and implications of snowpack spatial variability in this marginal setting. The distribution and dynamics of the snowpack were found to be influenced by upwind terrain, vegetation, solar radiation, and slope. The role of upwind vegetation was quantified using a novel parameter based on gridded vegetation height. The elevation range of the catchment was relatively modest (185 m), and elevation impacted distribution but not dynamics. Two characteristic features of marginal snowpack behaviour are presented. Firstly, the evolution of the snowpack is described in terms of a relatively unstable accumulation state and a highly stable ablation state, as revealed by temporal variations in the mean and standard deviation of snow water equivalent. Secondly, the validity of partitioning the snow season into distinct accumulation and ablation phases is shown to be compromised in such a setting. Snow at the most marginal locations may undergo complete melt several times during a season and, even where snow cover is more persistent, ablation processes begin to have an effect on the distribution of the snowpack early in the season. Our results are consistent with previous research showing that individual point measurements are unable to fully represent the variability in the snowpack across a catchment, and we show that recognising and addressing this variability are particularly important for studies in marginal snow environments.
Concordance with the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention and colorectal cancer risk in Morocco: A large, population‐based case–control study
Authors: El Kinany Khaoula , Huybrechts Inge , Kampman Ellen , Boudouaya Hanae Abir , Hatime Zineb , Mint Sidi Deoula Meimouna , El Asri Achraf , Benslimane Abdelilah , Nejjari Chakib , Ibrahimi Sidi Adil , Mrabti Hind , Abda Naima , Alaoui Rhimou , Gunter Marc J. , El Rhazi Karima
Published: March 2019

The present study aimed to investigate associations between adherence to the recommendations on cancer prevention from the WCRF/AICR and colorectal cancer (CRC) risk in Morocco. Incident CRC cases (n = 1,516) and controls (n = 1,516) matched on age, sex and center, were recruited between September 2009 and February 2017 at five major hospitals located in Morocco. In‐person interviews were conducted to assess habitual diet using a validated Food Frequency Questionnaire, physical activity and anthropometric measurements. Adherence to the WCRF/AIRC Recommendations was ranged from 0 (no adherence) to 6 (maximal adherence) and incorporating six WCRF/AICR components (food groups, physical activity and BMI). Multivariable odd ratios (ORA) and 95% confidence intervals (CI) were calculated using conditional multivariate logistic regression models, with low adherence as referent, adjusting for potential confounding factors. Compared to those with the lowest adherence score, individuals in the highest WCRF/AICR score category had a statistically significant reduced risk for colon cancer (ORA = 0.63, 95% CI 0.53–0.76); rectal cancer (ORA = 0.52, 95% CI 0.43–0.63) and CRC overall (ORA = 0.58, 95% CI 0.51–0.66). For individual score components, when comparing the lowest with the highest adherence category, CRC risk was significantly lower in the highest adherence category for body fatness (ORA = 0.73; 95% CI 0.62–0.85), physical activity (ORA = 0.70; 95% CI 0.60–0.82), plant foods (ORA = 0.50; 95% CI 0.39–0.63) and red/processed meat (ORA = 0.81; 95% CI 0.71–0.92). Our analysis indicated that greater adherence to the WCRF/AICR recommendations for cancer prevention may lower CRC risk in Morocco.
Statins and pancreatic cancer risk in patients with chronic pancreatitis: A Danish nationwide population‐based cohort study
Authors: Kirkegård Jakob , Lund Jennifer L. , Mortensen Frank Viborg , Cronin‐Fenton Deirdre
Published: March 2019

Statins (HMG‐CoA reductase inhibitors) have antiinflammatory and possibly anticancer properties. We hypothesized that statin use is associated with lower risk of pancreatic cancer in patients with chronic pancreatitis. This nationwide population‐based cohort study included all Danish patients diagnosed with incident chronic pancreatitis from 1 January 1996 to 31 December 2012. We used the Danish National Prescription Registry to ascertain information on statin prescriptions for members of the study population before and after their pancreatitis diagnosis. We computed crude incidence rates, incidence rate ratios (IRRs) and adjusted hazard ratios (HRs) with associated 95% confidence intervals (CIs) for pancreatic cancer, comparing statin users with nonusers. We computed HRs using Cox proportional hazards regression with statins treated as a time‐varying exposure lagged by 1 year, adjusting for age, sex, socioeconomic status and individual comorbidities. The study included 8,311 chronic pancreatitis patients with a median age of 54 years. We observed 153 pancreatic cancers during 60,365 person‐years of follow‐up. The unadjusted IRR comparing statin users with nonusers was 1.00 (95% CI: 0.60–1.60). Adjustment for potential confounders only had a small impact on the estimate (adjusted HR: 0.90; 95% CI: 0.56–1.44). Our findings suggest that statin use is not associated with pancreatic cancer risk in patients with chronic pancreatitis.
Absolute risks of cervical precancer among women who fulfill exiting guidelines based on HPV and cytology cotesting
Authors: Landy Rebecca , Schiffman Mark , Sasieni Peter D. , Cheung Li C. , Katki Hormuzd A. , Rydzak Greg , Wentzensen Nicolas , Poitras Nancy E. , Lorey Thomas , Kinney Walter K. , Castle Philip E.
Published: March 2019

US guidelines recommend that most women older than 65 years cease cervical screening after two consecutive negative cotests (concurrent HPV and cytology tests) in the previous 10 years, with one in the last 5 years. However, this recommendation was based on expert opinion and modeling rather than empirical data on cancer risk. We therefore estimated the 5‐year risks of cervical precancer (cervical intraepithelial neoplasia grade 3 or adenocarcinomain situ[CIN3]) after one, two and three negative cotests among 346,760 women aged 55–64 years undergoing routine cotesting at Kaiser Permanente Northern California (2003–2015). Women with a history of excisional treatment or CIN2+ were excluded. No woman with one or more negative cotests was diagnosed with cancer during follow‐up. Five‐year risks of CIN3 after one, two, and three consecutive negative cotests were 0.034% (95% CI: 0.023%–0.046%), 0.041% (95% CI: 0.007%–0.076%) and 0.016% (95% CI: 0.000%–0.052%), respectively (ptrend< 0.001). These risks did not appreciably differ by a positive cotest result prior to the one, two or three negative cotest(s). Since CIN3 risks after one or more negative cotests were significantly below a proposed 0.12% CIN3+ risk threshold for a 5‐year screening interval, a longer screening interval in these women is justified. However, the choice of how many negative cotests provide sufficient safety against invasive cancer over a woman's remaining life represents a value judgment based on the harmsversusbenefits of continued screening. Ideally, this guideline should be informed by longer‐term follow‐up given that exiting is a long‐term decision.
Successful treatment of ureteral stricture after total hysterectomy: An antegrade ureteroscopic approach facilitates the insertion of a guidewire for endoscopic dilation
Authors: Iwamoto Genta , Kawahara Takashi , Takeshima Teppei , Ninomiya Sahoko , Takamoto Daiji , Mochizuki Taku , Kuroda Shinnosuke , Yao Masahiro , Uemura Hiroji
Published: March 2019

Introduction

Iatrogenic ureteral injury is sometimes seen in daily clinical practice, and gynecological surgery carries the highest risk of ureteral injury among iatrogenic surgical ureteral injury.

Case presentation

A 61‐year‐old woman was referred to our department for right ureteral stricture and hydronephrosis after total hysterectomy. We initially attempted ureteral stenting, but hydronephrosis redeveloped 1 month after ureteral stent removal. We performed ureteroscopy via an antegrade approach and successfully incised and dilated the ureter.

Conclusion

We encountered a case of severe ureteral stenosis after total hysterectomy that was successfully treated endoscopically using ureteroscopy via an antegrade approach.
SWI post processing using granularity controlled edge‐preserved denoising of multichannel GRE images
Authors: Madhusoodhanan Sreekanth , Kesavadas Chandrasekharan , Paul Joseph S.
Published: March 2019

The influence of granularities in the background suppressed phase of susceptibility‐weighted images (SWI) and susceptibility‐weighted angiogram (SWAN) becomes significant when the susceptibility based contrast is enhanced by exponential weighting of the high‐pass filtered phase. Furthermore, the effect of noise due to the inherently low signal‐to‐noise ratio resulting from high‐resolution SWI/SWAN acquisition, can be minimized by application of edge‐preserved denoising of the channel phase images without loss of venous structural details. Simultaneous reduction of granularity effects with edge‐preserved denoising is achieved using the proposed granularity controlled adaptive edge‐preserved regularization (GRADER). In this approach, the edge‐preserving cost is minimized with respect to the desired channel phase image and an unknown scale parameter that adaptively tunes the high‐pass filter. The algorithm is implemented using quasi‐Newton type iterations, with the scale parameter updated using a search procedure in each alternating minimization step. The iterations are stopped once the scale parameter converges to a steady state value. Extension of GRADER to parallel MRI (pMRI) by processing the real and imaginary components of complex channel images (IR‐GRADER) results in enhanced susceptibility‐related contrast‐to‐noise ratio of the magnitude SWI, leading to improved visualization of superficial veins and deep gray matter structures.
Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue‐engineered cartilage
Authors: Lam Tobias , Dehne Tilo , Krüger Jan Philipp , Hondke Sylvia , Endres Michaela , Thomas Alexander , Lauster Roland , Sittinger Michael , Kloke Lutz
Published: March 2019

To create artificial cartilage in vitro, mimicking the function of native extracellular matrix (ECM) and morphological cartilage‐like shape is essential. The interplay of cell patterning and matrix concentration has high impact on the phenotype and viability of the printed cells. To advance the capabilities of cartilage bioprinting, we investigated different ECMs to create an in vitro chondrocyte niche. Therefore, we used methacrylated gelatin (GelMA) and methacrylated hyaluronic acid (HAMA) in a stereolithographic bioprinting approach. Both materials have been shown to support cartilage ECM formation and recovery of chondrocyte phenotype. We used these materials as bioinks to create cartilage models with varying chondrocyte densities. The models maintained shape, viability, and homogenous cell distribution over 14 days in culture. Chondrogenic differentiation was demonstrated by cartilage‐typical proteoglycan and type II collagen deposition and gene expression (COL2A1, ACAN) after 14 days of culture. The differentiation pattern was influenced by cell density. A high cell density print (25 × 106 cells/mL) led to enhanced cartilage‐typical zonal segmentation compared to cultures with lower cell density (5 × 106 cells/mL). Compared to HAMA, GelMA resulted in a higher expression of COL1A1, typical for a more premature chondrocyte phenotype. Both bioinks are feasible for printing in vitro cartilage with varying differentiation patterns and ECM organization depending on starting cell density and chosen bioink. The presented technique could find application in the creation of cartilage models and in the treatment of articular cartilage defects using autologous material and adjusting the bioprinted constructs size and shape to the patient. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2649–2657, 2019.
Biodegradable hyaluronan hydrogel coatings on acellular dermis grafts—A potential strategy to improve biologic graft durability in hernia repair application
Authors: Sahoo Sambit , Ma Jinjin , Tastaldi Luciano , Baker Andrew R. , Loftis Jacki , Rosen Michael J. , Derwin Kathleen A.
Published: March 2019

Biologic grafts used in hernia repair undergo rapid cellular infiltration and remodeling, but their premature degradation often results in hernia recurrence. We hypothesize that a temporary barrier that prevents infiltration of acute inflammatory cells into the graft during the initial 4 weeks of implantation could mitigate graft degradation. The purpose of this study is to design tyramine‐substituted hyaluronan (THA) hydrogel coatings with tunable degradation properties, as a means to develop a resorbable barrier for human acellular dermis grafts (HADM). THA plugs prepared at different cross‐linking densities, by varying cross‐linking agent concentration (0.0001–0.0075% H2O2), demonstrated varying rates ofin vitrodegradation (25 U/mL hyaluronidase, 48 h). Based on these results, HADM grafts were coated with THA at three cross‐linking densities (0.0001%, 0.00075%, and 0.003% H2O2) and THA coating degradation was evaluatedin vitro(25 U/mL hyaluronidase, 48 h) andin vivo(rat intraperitoneal implantation, 1–4 weeks). THA coatings degradedin vitroandin vivowith the lowest cross‐linking density (0.0001% H2O2), generally showing greater degradation as evidenced by significant decrease in coating cross‐sectional area. However, all three coatings remained partially degraded after 4 weeks ofin vivoimplantation. Alternate strategies to acceleratein vivodegradation of THA coatings are required to allow investigation of the study hypothesis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2664–2672, 2019.
In vitro PUVA treatment triggers calreticulin exposition and HMGB1 release by dying T lymphocytes in GVHD: New insights in extracorporeal photopheresis
Authors: Coppard Céline , Hannani Dalil , Humbert Marion , Gauthier Virginie , Plumas Joel , Merlin Etienne , Gabert Françoise , Chaperot Laurence
Published: March 2019

Background

Extracorporeal photopheresis (ECP) is an effective therapy for graft vs host disease (GVHD), based on infusion of UVA‐irradiated and 8 methoxy‐psoralen (PUVA)‐treated leukocytes. Reinfusion of these apoptosing cells affects the functionality of pathogenic T cells through poorly understood immunomodulatory mechanisms. Apoptosis is usually a silent, tolerance‐associated process, but can also be immunogenic, depending on death‐inducers and environmental context.

Methods

To understand ECP mechanisms of action, human alloreactive T cells generated in an in vitro model mimicking GVHD were used, as well as primary cells from GVHD patients. Cells were submitted to PUVA treatment and their phenotype and immunogenicity were analyzed, using cell culture and flow cytometry.

Results

In vitro PUVA treatment induced the expression of several damage‐associated molecular patterns (DAMPs) by dying T cells (calreticulin, high‐mobility group box‐1, and to a lesser extent heat shock proteins 70 and 90), especially upon T cell activation, leading to their phagocytosis by macrophages and dendritic cells (DCs). Allogeneic DCs preincubated with PUVA treated T cells induced comparable naive T cell proliferation and polarization as control allogeneic DC.

Conclusion

Altogether, in our experimental settings, in vitro PUVA‐treatment induces a partially immunogenic phenotype allowing phagocytosis of apoptotic cells by macrophages and DC, however not sufficient to induce dendritic cell maturation and T cell activation. These data refine current models of ECP‐mediated immune modulation and emphasize the need to further analyze PUVA‐treated cell interactions with immune cells.
Circulating microRNA‐133, microRNA‐17 and microRNA‐25 in serum and its potential diagnostic value in gastric cancer
Authors: ZiaSarabi Parisa , Sorayayi Saba , Hesari AmirReza , Ghasemi Faezeh
Published: March 2019

Gastric cancer is one of the most common malignancies in the world and is considered as the most lethal gastrointestinal cancer. microRNAs (miRNAs) can be very important in detecting a disease at an early stage. The aim of this study was to investigate the microRNA‐17 (miR‐17), miR‐25, and miR‐133b in the serum of gastric cancer subjects. Serum samples were obtained from 120 gastric cancers and 102 healthy subjects. We evaluated expression levels of miR‐17, miR‐25 and miR‐133b by quantitative real‐time polymerase chain reaction. Our results showed that in the patients with gastric cancer, the expression level of miR‐17 and miR‐25 were significantly increased compared with the control group (P < 0.5), while the expression level of miR‐133b was significantly decreased in patient groups compared with control cases (P < 0.5). It seems that expression of miRNAs in Iranian patients with gastric cancer is similar to other patients in other populations. These findings suggested that miR‐17, miR‐25 and miR‐133b could be introduced as potential diagnostic candidates for the detection in gastric cancer patients in the early stage.
Reduning injection ameliorates paraquat‐induced acute lung injury by regulating AMPK/MAPK/NF‐κB signaling
Authors: Jiang Cuihua , Zhong Rongling , Zhang Jian , Wang Xiangxiang , Ding Gang , Xiao Wei , Ma Shiping
Published: March 2019

Reduning injection (RDN), a patented Chinese medicine, is broadly used for common cold and lung infection in clinic, but the mechanism underlying its effects on inflammation‐related pulmonary injury remains unclear. Paraquat (PQ, bolus 15 mg/kg dose, ip) was administered for acute lung injury induction in mice, which were orally administered dexamethasone (2 mg/kg) or RDN (50 and 100 mg/kg/day) for 5 days. After treatment, plasma and lung tissue samples from the euthanized animals were obtained and analyzed by histological, biochemical and immunoblot assays. Histological observation demonstrated RDN alleviated PQ‐induced lung damage. Meanwhile, RDN suppressed myeloperoxidase (MPO) activity, reduced the wet/dry (W/D) ratio and decreased the amounts of total leukocytes and neutrophils. Treatment also markedly decreased the amounts of malondialdehyde, MPO, and inflammatory cytokines while increasing superoxide dismutase activity in comparison with the PQ group. In immunoblot, RDN blocked the phosphorylation levels of adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK), JNK, ERK, p38, inhibitor of nuclear factor κB kinase and nuclear factor‐κB (NF‐κB) in lung tissue specimens in PQ‐challenged animals, which was further verified in vitro. The above data indicated protective effects for RDN in PQ‐induced lung damage, possibly through inhibition of the AMPK/MAPK/NF‐κB pathway.
In utero transplantation of neural stem cells ameliorates maternal inflammation‐induced prenatal white matter injury
Authors: Borhani‐Haghighi Maryam , Mohamadi Yousef , Kashani Iraj Ragerdi
Published: March 2019

Prenatal white matter injury is a serious problem due to maternal inflammation leading to postnatal disabilities. In this study, we used the periventricular leukomalacia (PVL) model as a common prenatal white matter injury by maternal administration of lipopolysaccharide (LPS). Neural stem cells (NSCs) have shown therapeutic ability in neurological disorders through a different mechanism such as immunomodulation. Here, we studied the preventive potential of NSCs following in utero transplantation into the embryonic lateral ventricle in an LPS‐induced white matter injury model. Pregnant animals were divided into three groups and received phosphate buffered saline, LPS, or LPS + NSCs. The brains of offspring were obtained and evaluated by real‐time polymerase chain reaction (PCR), immunohistochemy, enzyme‐linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase‐mediated biotinylated‐dUTP nick‐end labeling (TUNEL), and caspase‐3 activity assay. The LPS‐induced maternal inflammation degenerated the myelin sheath in the offspring periventricular region which was associated with an increased microglial number, oligodendrocytes degeneration, proinflammatory cytokine secretion, and cell apoptosis. The transplanted NSCs homed into the brain and ameliorated the evaluated parameters. The expression of proinflammatory cytokines interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α), cell apoptosis and caspase‐3 activity were inhibited by NSCs. In addition, Olig2 and myelin basic protein immunohistochemy staining showed that prenatal NSCs transplantation augmented the myelination in the periventricular white matter of offspring. In conclusion, we think that prenatal therapeutic strategies, such as in utero NSCs transplantation, may prevent prenatal white matter injury after birth.
Association between rs4938723 polymorphism and the risk of primary open‐angle glaucoma (POAG) in a Chinese population
Authors: Zhang Jian , Wang Li
Published: March 2019

In this study, we aimed to investigate the association between rs4938723 single‐nucleotide polymorphism (SNP) and the risk of primary open‐angle glaucoma (POAG) in a Chinese population to clarify the molecular mechanism underlying the pathogenesis of POAG. Taqman assays and statistical analyses were utilized to analysis the associations between rs4938723 SNP/rs1042522 SNP and the risk of POAG. Luciferase assays, in‐silicon analyses, real‐time PCR, Western Blot, 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT) assay, and flow cytometry were conducted to establish a molecular pathway underlying the protective effect of rs4938723 T > C SNP against the risk of POAG. The maximum intraocular pressure (IOP) was evidently higher in the case group compared with that in the control group. The risk of POAG was evidently decreased among carriers of the CT/CC genotypes under a dominant model. In addition, the risk of POAG was also significantly decreased in the carriers of the CC genotype. In contrary, no significant association was found between the risk of POAG and the rs1042522 SNP in
TP53 gene. In addition, rs4938723 (especially rs4938723 T > C) SNP could elevate the transcription efficiency of miR‐34b promoter and the suppression of TP53, a virtual target of miR‐34b. Therefore, the presence of anti‐miR‐34b suppressed cell proliferation and promoted cell apoptosis, thus establishing a molecular mechanism underlying the protective effect of rs4938723 polymorphism T > C against the risk of POAG. Rs4938723 polymorphism T > C could reduce the incidence of POAG by downregulating TP53 expression, thus leading to suppressed cell apoptosis and enhanced cell proliferation.
PIAS genes as disease markers in bipolar disorder
Authors: Sayad Arezou , Taheri Mohammad , Azari Iman , Oskoei Vahid Kholghi , Ghafouri‐Fard Soudeh
Published: March 2019

The protein inhibitors of activated STAT (PIAS) are involved in regulation of many transcription factors and signaling pathways that contribute to the pathogenesis of bipolar disease (BD). In the current study, we evaluated the expression of four PIAS genes (PIAS1‐4) in peripheral blood of BD patients and healthy subjects to explore their contribution in the pathogenesis of BD and their suitability as peripheral biomarkers for this disorder. All PIAS genes were significantly upregulated in total BD patients compared with total controls. The sex‐based analysis confirmed upregulation of PIAS1‐4 genes in male BD patients compared with male controls (P < 0.001). However, PIAS1 was significantly downregulated in female patients compared with female controls (P = 0.02). Expression levels of other PIAS genes were not significantly different between female patients and female controls. There were no significant correlations between expression levels of PIAS genes and any of the clinical data of study participants after adjustment of the effects of the sex. On the basis of the area under the curve (AUC) values in receiver operating characteristic curves, PIAS4 had the best performance in the differentiation of disease status between study participants (AUC = 0.81). PIAS3 and PIAS4 genes had the best sensitivity and specificity values, respectively. Combination of expression levels of four genes resulted in the improvement of diagnostic power (AUC = 0.82). The current data implies the role of PIAS genes in the pathogenesis of BD and denotes their suitability as peripheral markers for this disorder.
Comprehensive analyses of DNA methylation and gene expression profiles of Kawasaki disease
Authors: Chang Danqi , Qian Cheng , Li Hang , Feng Hong
Published: March 2019

Objective

Kawasaki disease (KD) is a childhood febrile vasculitis with unknown etiology. Epigenetic regulation in the gene expression dynamics has become increasingly important in KD. Thus, we performed an integrated analysis of DNA methylation and gene expression data to identify novel molecular mechanisms and key functional genes in KD.

Methods

DNA methylation (GSE84624) and gene expression (GSE68004) datasets were downloaded from Gene Expression Omnibus. Methylated‐differentially expressed genes (mDEGs) were documented as the overlapping genes between the differentially methylated genes (DMGs) in GSE84624 and differentially expressed genes (DEGs) in GSE68004. Functional enrichment analyses of the mDEGs were conducted using DAVID database. Protein‐protein interaction (PPI) network was then constructed to obtain the hub genes involved in KD using STRING database.

Results

A total of 1389 DMGs and 1362 DEGs were screened out between KD and control samples. Overlapping of them resulted in four hypermethylated/downregulated and 187 hypomethylated/upregulated genes. These mDEGs were mainly enriched in inflammation response, innate immune response, and blood coagulation, and signaling pathways such as platelet activation, osteoclast differentiation, and chemokine signaling pathway. PPI network analyses identified MAPK14 and PHLPP1 as the hub genes involved in KD, which could distinguish KD from other common pediatric febrile diseases. In addition, the methylation and expression levels of MAPK14 and PHLPP1 were validated in other independent datasets.

Conclusion

This study provides an integrated view of interactions among DNA methylation and gene expression in patients with KD. MAPK14 and PHLPP1 are the key genes influenced by methylation and may serve as candidate biomarkers for KD.
Evaluation of the BioPlex 2200 syphilis total screen (IgG/IgM) with reflex to an automated rapid plasma reagin test
Authors: Rourk Angela R. , Litwin Christine M.
Published: March 2019

Background

We evaluated the recently FDA cleared BioPlex 2200 Syphilis Total Screen and automated rapid plasma reagin (RPR) assay for the detection of total (IgG/IgM) treponemal and non‐treponemal antibodies in the reverse syphilis algorithm.

Methods

Prospectively submitted samples (n = 885) were assayed by both the IgG/IgM BioPlex Syphilis Screen and the original IgG BioPlex Syphilis Screen. The IgG screen reactive samples were reflexed to traditional RPR, and IgG/IgM screen reactive samples were reflexed to the automated RPR. Nonreactive RPR samples were tested by the Treponemal Pallidum Particle Agglutination test (TP‐PA). Additional samples were collected (n = 404 total samples) to directly compare the automated and traditional RPR assays with each other.

Results

The sensitivity and specificity of the IgG/IgM screen with automated RPR was 95.6% (95% confidence interval [CI] 87.0‐99.1) and 99.6% (CI 99.2‐99.8) while the sensitivity and specificity of the BioPlex IgG screen with traditional RPR was 97.8% (CI 89.1‐99.9) and 99.3% (CI 98.8‐99.4). The sensitivity and specificity of the BioPlex RPR compared with traditional RPR was 95.8% (CI 93.9‐97.0) and 94.1% (CI 89.4‐91.1) and 95.3% (CI 92.6‐97.1). The mean of the titer differences between the BioPlex RPR and the traditional RPR was 1.0 ± 0.9 SD titers.

Conclusion

The addition of the detection of treponemal IgM antibodies to the IgG/IgM screen did not significantly affect the sensitivity and specificity compared to the original IgG screen. However, the addition of the comparable BioPlex RPR assay to the instrumentation significantly reduces the overall labor of syphilis screening and confirmation.
Genetic counseling for consumer‐driven whole exome and whole genome sequencing: A commentary on early experiences
Authors: Schmidt Johanna L. , Maas Roxanne , Altmeyer Sharon Reid
Published: March 2019

Counseling after consumer‐driven whole exome sequencing (WES) and whole genome sequencing (WGS) presents challenges for genetic counselors as availability of this testing increases. There are no standard practice guidelines and limited resources for genetic counselors in this area, but consumer demand for counseling and data interpretation exists and is likely to grow along with testing opportunities. In this paper, we comment upon our experiences as three independent, private practice genetic counselors who have provided counseling services for clients with WES/WGS reports and data. In our counseling experience, we have encountered three main types of client motivation for seeking testing and counseling: generally healthy individuals who are curious to learn more about their genomic data, individuals with family histories of various conditions, and/or who want to better understand specific disease risks, and individuals who are ill, undiagnosed and searching for an understanding of their ailments. Research is needed to better understand client motivations for undergoing testing and counseling, as well outcomes of counseling sessions. In addition to improvements in variant identification, classification and bioinformatics, there is a need for practice guidelines, counseling resources, service delivery models, and efforts to increase awareness and access to genetic counseling services.
Usefulness of ultrasonographic evaluation of stool and/or gas distribution for the treatment strategy of chronic constipation
Authors: Manabe Noriaki , Kamada Tomoari , Kusunoki Hiroaki , Hata Jiro , Haruma Ken
Published: March 2019

Background and Aim

This study aimed to evaluate the capability of ultrasonography to predict favorable outcomes of various medical therapies in patients with chronic constipation.

Methods

We enrolled 223 patients with chronic constipation (75 men, 148 women; mean age 62.9 ± 3.4 years). Transverse diameters of four segments of the colon (ascending [A], transverse [T], descending [D], sigmoid [S]), and the rectum [R]) were measured. The patients' stool and/or gas distribution was evaluated using the constipation index (CI) ([A + T + D + S + R]/5) and the left/right distribution ratio ([D + S]/[A + T]) according to our previous study. Patients were first treated with fiber‐ or osmosis‐based laxatives for 2 weeks. When constipation was not alleviated, stimulant‐based laxatives were added, and the patients were followed for another 2 weeks.

Results

Based on their clinical courses, patients were divided into four groups: nonresponders (group A) or responders (group B) to fiber‐ or osmosis‐based laxatives; nonresponders to any medical therapy (group C); and responders to stimulant‐based laxatives (group D). The CI was significantly higher in group A than group B (P < 0.05), with the receiver operating characteristic (ROC) curve analysis showing a CI cut‐off of 21.2 for predicting favorable outcomes of either fiber‐ or osmosis‐based laxatives (P < 0.05). Left/right distribution ratio was significantly lower in group C than group D (P < 0.05), and the ROC curve analysis showed a left/right cut‐off of 0.5 for predicting responders to stimulant‐based laxatives (P < 0.05).

Conclusion

These findings could help physicians predict favorable outcomes with laxatives without side effects for this patient population.
Patterns of alcohol consumption and nutrition intake in patients with alcoholic liver disease and alcoholic pancreatitis in North Indian men
Authors: Singh Karam R , Muktesh Gaurav , Gunjan Deepak , Kochhar Rakesh , Singh Virendra , Das Ashim , Siddappa Pradeep , Singh Kartar
Published: March 2019

Background and Aim

Chronic alcoholism and nutrition play an important role in liver and pancreatic diseases. To compare drinking habits and nutritional data in patients with alcoholic liver disease (ALD) and alcoholic pancreatitis (ALP).

Methods

Clinical, anthropometric, dietary intake, laboratory, and imaging data were recorded in consecutive patients of ALD and ALP.

Results

In 150 patients of ALP (n = 76) and ALD (n = 74), the age of starting alcohol consumption (19.03 ± 3.78 vs 18.0 ± 2.59 years) and the mean amount of alcohol consumed per day (165.63 ± 87.99 vs 185.50 ± 113.54 g; P = 0.230) were similar. Patients with ALD consumed alcohol on a daily basis more frequently (90.5 vs 72.3%; P = 0.003) and had a longer duration of alcohol intake (21.6 + 0.2 vs 14.5 + 6.9 years; P < 0.0001) than patients in the ALP group. Binge drinking was more common in patients with ALP compared to patients with ALD (60.5 vs 20.3%); P < 0.0001). Patients with ALP had a lower body mass index (19.9 ± 3.49 vs 22.64 ± 4.88 kg/m2; P = 0.001) and more frequent decrease in mid arm circumference (57.9 vs 44.6%; P = 0.042) and triceps skin fold thickness (67.1 vs 52.7%; P = 0.072) compared to patients with ALD.

Conclusion

There was no difference in the age of starting alcohol consumption and mean amount of alcohol consumption per day between the groups. Patients with ALD were more likely to be daily drinkers with a longer duration of alcohol intake. However, binge drinking and malnourishment was more common in the ALP group.
MDM2 and its functional polymorphism SNP309 contribute to the development of esophageal carcinoma
Authors: Xiao Fan‐kai , Guo Sen , Yang Fan , Zhao Luo‐sha , Wang Li‐dong
Published: March 2019

Background

Overexpression of the murine double minute 2 (MDM2) has been explored in many tumors with high proliferation and anti‐apoptosis ability. However, the role of MDM2 and its functional single nucleotide polymorphism (SNP) rs2279744 (also known as SNP309) in esophageal squamous cell carcinoma (ESCC) remains unclear.

Methods

We performed a genotype study of blood samples in 360 ESCC patients and 360 healthy control individuals to determine the risk of various rs2279744 in ESCC. To further evaluate the role of rs2279744 in regulating MDM2 expression, we performed an allele‐specific reporter assay and investigated whether the SNP‐containing sequences functioned as an active enhancer. To examine the functional role of MDM2 on esophageal cancer cell lines, we carried out an MTS assay and flow cytometry analysis.

Results

From the genotyping study, we found that GG genotype of SNP309 significantly increased the risk of ESCC in an additive model [odds ratio (OR) = 2.55, 95% confidence interval (CI) = 1.66–3.89, p = 1.50 × 10–5) and in a recessive model (OR = 2.44, 95% CI = 1.69–3.51, p = 1.60 × 10–8). Furthermore, the G allele was significantly associated with a higher risk of ESCC (OR = 1.56, 95% CI = 1.26–1.92, p = 2.81 × 10–5). In multivariate logistic regression analysis, the GG genotype had increased the occurrence of ESCC by 2.39‐fold (95% CI = 1.48–3.8). Compared to the T allele, the variant G allele had significantly higher luciferase activity on the promoter of MDM2 in both cell lines. By transfecting the gene to ESCC lines, we showed that overexpression of MDM2 significantly promote cell proliferation and anti‐apoptosis.

Conclusions

The MDM2 promoter SNP309 is a risk factor for esophageal cancer. MDM2 promotes the proliferation and anti‐apoptosis of ESCC.
Measuring tissue sodium concentration: Cross‐vendor repeatability and reproducibility of 23Na‐MRI across two sites
Authors: Riemer Frank , McHugh Damien , Zaccagna Fulvio , Lewis Daniel , McLean Mary A. , Graves Martin J. , Gilbert Fiona J. , Parker Geoff J.M. , Gallagher Ferdia A.
Published: March 2019

Background

Sodium MRI (23Na‐MRI)‐derived biomarkers such as total sodium concentration (TSC) have the potential to provide information on tumor cellularity and the changes in tumor microstructure that occur following therapy.

Purpose

To evaluate the repeatability and reproducibility of TSC measurements in the brains of healthy volunteers, providing evidence for the technical validation of 23Na‐MRI‐derived biomarkers.

Study Type

Prospective multicenter study.

Subjects

Eleven volunteers (32 ± 6 years; eight males, three females) were scanned twice at each of two sites.

Field Strength/Sequence

Comparable 3D‐cones 23Na‐MRI ultrashort echo time acquisitions at 3T.

Assessment

TSC values, quantified from calibration phantoms placed in the field of view, were obtained from white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF), based on automated segmentation of coregistered 1H T1‐weighted images and hand‐drawn regions of interest by two readers.

Statistical Tests

Coefficients of variation (CoVs) from mean TSC values were used to assess intrasite repeatability and intersite reproducibility.

Results

Mean GM TSC concentrations (52.1 ± 7.1 mM) were ∼20% higher than for WM (41.8 ± 6.7 mM). Measurements were highly repeatable at both sites with mean scan–rescan CoVs between volunteers and regions of 2% and 4%, respectively. Mean intersite reproducibility CoVs were 3%, 3%, and 6% for WM, GM, and CSF, respectively.

Data Conclusion

These results demonstrate technical validation of sodium MRI‐derived biomarkers in healthy volunteers. We also show that comparable 23Na imaging of the brain can be implemented across different sites and scanners with excellent repeatability and reproducibility.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:1278–1284.
Age‐related deep white matter changes in myelin and water content: A T2 relaxometry study
Authors: Papadaki Efrosini , Kavroulakis Eleftherios , Kalaitzakis Georgios , Karageorgou Dimitra , Makrakis Dimitrios , Maris Thomas G. , Simos Panagiotis G.
Published: March 2019

Background

According to the retrogenesis hypothesis, the rate of age‐related changes in white matter (WM) myelin content varies between early myelinating (parietal, occipital) and late myelinating (prefrontal, lateral–posterior temporal) areas. The multiecho spin echo (MESE), PD‐to‐T2‐weighted sequence provides an index of myelin content (myelin water fraction [MWF]) derived from measurements of myelin water (via the short T2 component [10–50 msec]) and intra‐ and extracellular water (via the long T2 component [>50–200 msec]).

Purpose

To assess the shape and regional variations in the rate of age‐related myelin and water content changes in deep WM regions using the MESE sequence.

Study Type

Prospective, cross‐sectional.

Population

In all, 90 healthy adults aged 22–81 years.

Field Strength/Sequence

1.5T/ T1w, T2w, fluid attenuated inversion recovery (FLAIR), MESE sequences.

Assessment

Short T2, long T2, and MWF values were measured in prefrontal, parietal, lateral–posterior temporal, and occipital normal‐appearing WM (NAWM) areas.

Statistical Tests

Linear and quadratic effects of age on long T2 and MWF were assessed through regression analyses. Regional variations in the effect of age on long T2 and MWF values at both the individual and group level were examined, using regression and analysis of covariance (ANCOVA) analyses, respectively, controlling for total WM volume.

Results

The rate of age‐related changes in long T2 and MWF was higher for older persons and a significant increase or decline, respectively, was first noted at 60–69 years (P < 0.0033). MWF values peaked earlier (at 30 years of age) and displayed a steeper age‐related reduction in prefrontal and lateral–posterior temporal NAWM as compared with the occipital lobes (P < 0.05). The opposite pattern of age‐related effect was found for long T2 values.

Data Conclusion

Significant age‐related reductions in myelin content were closely followed by corresponding increases in intra‐ and extracellular water content. These changes were more pronounced among elderly people and followed an anterior–posterior pattern.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:1393–1404.