bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective randomised clinical trial of intravitreal bevacizumab versus triamcinolone in eyes with diabetic macular oedema undergoing cataract surgery: 6-month results
Authors: Kandasamy Rathika , Constantinou Marios , Rogers Sophie L , Sandhu Sukhpal Singh , Wickremasinghe Sanjeewa , Al-Qureshi Salmaan , Lim Lyndell L 
Published: February 2019

AimTo report the 6-month results of a clinical trial that compared intravitreous bevacizumab (BVB) 1.25 mg versus triamcinolone acetonide (TA) 4 mg when administered as an adjunct during cataract surgery to patients with diabetic macular oedema (DMO).MethodsProspective, double-masked, single-centre (Royal Victorian Eye and Ear Hospital, Melbourne) clinical trial. Patients with visually significant cataract and centre-involving DMO (either current or prior) were randomised (1: 1) to receive either intravitreous BVB 1.25 mg or TA 4 mg at the time of cataract surgery and if required at review. Main outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline to the 6-month time point of this 12-month study.Results61 eyes of 58 patients were enrolled. At baseline, both groups were similar in terms of BCVA and CMT (p>0.2). At 6 months, there was no significant difference in vision between the groups, with mean letter gain of +21.4 (95% CI +14.5 to +28.4) in the TA group and +17.3 (95% CI +12.1 to +22.6) in the BVB group (p=0.35). The TA group had a significant sustained anatomical improvement at 6 months, with a reduction in CMT (−51.4 µm; 95% CI −98.2 to -4.7) compared with thickening in the BVB group (+15.6 µm; 95% CI −26.4 to +57.7, p=0.04).ConclusionsWhen given as an adjunct to cataract surgery, both TA and BVB improved visual outcomes at 6 months postoperatively. However, only TA resulted in sustained improvement in CMT, with the majority not requiring any further treatment postoperatively.
Cytomegalovirus colitis in inflammatory bowel disease and after haematopoietic stem cell transplantation: diagnostic accuracy, predictors, risk factors and disease outcome
Authors: Mavropoulou Eirini , Ternes Kristin , Mechie Nicolae-Catalin , Bremer Sebastian Christopher Benjamin , Kunsch Steffen , Ellenrieder Volker , Neesse Albrecht , Amanzada Ahmad 
Published: February 2019

BackgroundConcurrent cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) and after haematopoietic stem cell transplantation (HSCT) is an important clinical entity associated with high rates of morbidity and mortality.MethodsA retrospective study of 47 patients with IBD and 61 HSCT patients was performed regarding the evaluation of diagnostic accuracy of applied methods, predictors, risk factors for CMV disease manifestation, the proportion of patients with antiviral treatment and disease outcome.ResultsThe sensitivity of quantitative PCR (qPCR) with a cut-off value of >250 copies/mg for CMV colitis in patients with IBD and HSCT patients was 79% and 92%, respectively. Predictors for CMV colitis in the IBD cohort were anaemia and the presence of endoscopic ulcers. Glucocorticoids, calcineurin inhibitors and >2 concurrent lines of treatment with immunosuppressive drugs could be identified as risk factors for CMV colitis in the IBD cohort with an OR of 7.1 (95% CI 1.7 to 29.9), 21.3 (95% CI 2.4 to 188.7) and 13.4 (95% CI 3.2 to 56.1), respectively. Predictors and risk factors for CMV gastroenteritis in the HSCT cohort was the presence of endoscopic ulcers (OR 18.6, 95% CI 3.3 to 103.7) and >2 concurrent lines of treatment with immunosuppressive drugs. Antiviral therapy was administered in 70% of patients with IBD and 77% of HSCT patients with CMV disease. 71% of antiviral-treated patients with IBD showed an improvement of their disease activity and 14% underwent colectomy. The mortality rate of HSCT patients was 21% irrespective of their CMV status.ConclusionsIn addition to the implementation of histological methods, qPCR may be performed in patients with suspected high-risk IBD and HSCT patients for CMV colitis. Independent validations of these results in further prospective studies are needed.
Novel mainstream capnometer system is safe and feasible even under CO2insufflation during ERCP-related procedure: a pilot study
Authors: Takimoto Yoichi , Iwasaki Eisuke , Masaoka Tatsuhiro , Fukuhara Seiichiro , Kawasaki Shintaro , Seino Takashi , Katayama Tadashi , Minami Kazuhiro , Tamagawa Hiroki , Machida Yujiro , Ogata Haruhiko , Kanai Takanori 
Published: February 2019

Background and aimsThere is a need to safely achieve conscious sedation during endoscopic retrograde cholangiopancreatography (ERCP). We evaluated the safety and feasibility of a mainstream capnometer system to monitor apnoea during ERCP under CO2insufflation.MethodsNon-intubated adult patients undergoing ERCP-related procedures with intravenous sedation were enrolled. End-tidal CO2(EtCO2) was continuously monitored during the procedure under CO2insufflation using a mainstream capnometer system, comprising a capnometer and a specially designed bite block for upper gastrointestinal endoscopy and ERCP. Oxygen saturation (SpO2) was also monitored continuously during the procedure. In this study, we evaluated the safety and feasibility of the capnometer system.ResultsEleven patients were enrolled. Measurement of EtCO2concentration was possible from the beginning to the end of the procedure in all 11 cases. There was no measurement failure, dislocation of the bite block, or adverse event related to the bite block. Apnoea linked to hypoxaemia occurred five times (mean duration, 174.4 s).ConclusionThis study confirmed that apnoea was detected earlier than when using a percutaneous oxygen monitor. Measurement of EtCO2concentration using the newly developed mainstream capnometer system was feasible and safe even under CO2insufflation.
GPs’ views and experiences of managing patients with personality disorder: a qualitative interview study
Authors: French Lydia , Moran Paul , Wiles Nicola , Kessler David , Turner Katrina M 
Published: February 2019

ObjectiveThe aim of this study was to explore GPs’ views and experiences of managing patients with personality disorder (PD), and their views on the role of the Improving Access to Psychological Therapies (IAPT) programme as a support service.DesignIn-depth interviews, analysed thematically.ParticipantsFifteen GPs (7 women and 8 men) of varying age and clinical experience, working in practices that differed in terms of the socio-demographic characteristics of their patient populations.SettingTwelve general practices based in the West of England, UK.ResultsGPs described patients with PD as being challenging to work with and that this work required dedicated time and care. They described experiencing particular difficulty with monitoring their patient’s mental health, as well as having little knowledge about the efficacy or availability of treatments for their attenders with PD. They were aware that this patient population often experienced poor mental health and reported a propensity for them to fall into the gap between primary and secondary mental health services, leaving GPs with little choice but to improvise their own management plans, which occasionally involved funding third-sector treatment options. In terms of IAPT services’ role in managing these patients, GPs wanted shorter waiting times, better inter-agency communication, more highly trained therapists and more treatment options for patients with PD. They also wanted the service to be able to ‘hold’ patients with PD in treatment over a longer period than currently offered.ConclusionsFindings suggest that, overall, GPs did not consider National Health Service mental health services to offer an effective treatment for patients with PD. While they considered the IAPT programme to be a valuable service for patients with less complex mental health needs, such as depression and anxiety; they felt that the current service provision struggled to meet the needs of patients with more complex mental health needs, as exemplified by people with PD.
Cardiovascular risk factors and disease among non-European immigrants living in Catalonia
Authors: Cainzos-Achirica Miguel , Vela Emili , Cleries Montse , Bilal Usama , Mauri Josepa , Pueyo Maria Jesus , Rosas Alba , Enjuanes Cristina , Blaha Michael J , Kanaya Alka M , Comin-Colet Josep 
Published: February 2019

ObjectiveTo describe the prevalence and incidence of cardiovascular risk factors, established cardiovascular disease (CVD) and cardiovascular medication use, among immigrant individuals of diverse national origins living in Catalonia (Spain), a region receiving large groups of immigrants from all around the world, and with universal access to healthcare.MethodsWe conducted a population-based analysis including >6 million adult individuals living in Catalonia, using the local administrative healthcare databases. Immigrants were classified in 6 World Bank geographic areas: Latin America/Caribbean, North Africa/Middle East, sub-Saharan Africa, East Asia and South Asia. Prevalence calculations were set as of 31 December 2017.ResultsImmigrant groups were younger than the local population; despite this, the prevalence of CVD risk factors and of established CVD was very high in some immigrant subgroups compared with local individuals. South Asians had the highest prevalence of diabetes, and of hyperlipidemia among adults aged <55 years; hypertension was highly prevalent among sub-Saharan Africans, and obesity was most common among women of African and South Asian ancestry. In this context, South Asians had the highest prevalence of coronary heart disease across all groups, and of heart failure among women. Heart failure was also highly prevalent in African women.ConclusionsThe high prevalence of risk factors and established CVD among South Asians and sub-Saharan Africans stresses the need for tailored, aggressive health promotion interventions. These are likely to be beneficial in Catalonia, and in countries receiving similar migratory fluxes, as well as in their countries of origin.
Blocked cats and limited finances: an ethical obstruction?
Authors: Williams David 
Published: February 2019

This series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Blocked cats and limited finances: an ethical obstruction?’, was submitted and is discussed by David Williams. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue.The series is being coordinated by Steven McCulloch, senior lecturer in human animal studies at the Centre for Animal Welfare, University of Winchester. It aims to provide a framework that will help practising veterinarians find solutions when facing similar dilemmas.
Chance to cut: defining a negative exploration rate in patients with suspected necrotizing soft tissue infection
Authors: Howell Erin C , Keeley Jessica A , Kaji Amy H , Deane Molly R , Kim Dennis Y , Putnam Brant , Lee Steven L , Woods Alexis L , Neville Angela L 
Published: February 2019

BackgroundNecrotizing soft tissue infections (NSTI) are aggressive infections associated with significant morbidity and mortality. Despite multiple predictive models for the identification of NSTI, a subset of patients will not have an NSTI at the time of surgical exploration. We hypothesized there is a subset of patients without NSTI who are clinically indistinguishable from those with NSTI. We aimed to characterize the differences between NSTI and non-NSTI patients and describe a negative exploration rate for this disease process.MethodsWe conducted a retrospective review of adult patients undergoing surgical exploration for suspected NSTI at our county-funded, academic-affiliated medical center between 2008 and 2015. Patients were identified as having NSTI or not (non-NSTI) based on surgical findings at the initial operation. Pathology reports were reviewed to confirm diagnosis. The NSTI and non-NSTI patients were compared using χ2test, Fisher’s exact test, and Wilcoxon rank-sum test as appropriate. A p value <0.05 was considered significant.ResultsOf 295 patients undergoing operation for suspected NSTI, 232 (79%) were diagnosed with NSTI at the initial operation and 63 (21%) were not. Of these 63 patients, 5 (7.9%) had an abscess and 58 (92%) had cellulitis resulting in a total of 237 patients (80%) with a surgical disease process. Patients with NSTI had higher white cell counts (18.5 vs. 14.9 k/mm3, p=0.02) and glucose levels (244 vs. 114 mg/dL, p<0.0001), but lower sodium values (130 vs. 134 mmol/L, p≤0.0001) and less violaceous skin changes (9.2% vs. 23.8%, p=0.004). Eight patients (14%) initially diagnosed with cellulitis had an NSTI diagnosed on return to the operating room for failure to improve.ConclusionsClinical differences between NSTI and non-NSTI patients are subtle. We found a 20% negative exploration rate for suspected NSTI. Close postoperative attention to this cohort is warranted as a small subset may progress.Level of evidenceRetrospective cohort study, level III.
A Functional Landscape of Resistance to MEK1/2 and CDK4/6 Inhibition in NRAS-Mutant Melanoma
Authors: Hayes Tikvah K. , Luo Flora , Cohen Ofir , Goodale Amy B. , Lee Yenarae , Pantel Sasha , Bagul Mukta , Piccioni Federica , Root David E. , Garraway Levi A. , Meyerson Matthew , Johannessen Cory M. 
Published: February 2019

Abstract

Combinatorial inhibition of MEK1/2 and CDK4/6 is currently undergoing clinical investigation in NRAS-mutant melanoma. To prospectively map the landscape of resistance to this investigational regimen, we utilized a series of gain- and loss-of-function forward genetic screens to identify modulators of resistance to clinical inhibitors of MEK1/2 and CDK4/6 alone and in combination. First, we identified NRAS-mutant melanoma cell lines that were dependent on NRAS for proliferation and sensitive to MEK1/2 and CDK4/6 combination treatment. We then used a genome-scale ORF overexpression screen and a CRISPR knockout screen to identify modulators of resistance to each inhibitor alone or in combination. These orthogonal screening approaches revealed concordant means of achieving resistance to this therapeutic modality, including tyrosine kinases, RAF, RAS, AKT, and PI3K signaling. Activated KRAS was sufficient to cause resistance to combined MEK/CDK inhibition and to replace genetic depletion of oncogenic NRAS. In summary, our comprehensive functional genetic screening approach revealed modulation of resistance to the inhibition of MEK1/2, CDK4/6, or their combination in NRAS-mutant melanoma.

Significance:
These findings reveal that NRAS-mutant melanomas can acquire resistance to genetic ablation of NRAS or combination MEK1/2 and CDK4/6 inhibition by upregulating activity of the RTK–RAS–RAF and RTK–PI3K–AKT signaling cascade.
Label-Free Raman Spectroscopy Reveals Signatures of Radiation Resistance in the Tumor Microenvironment
Authors: Paidi Santosh K. , Diaz Paola Monterroso , Dadgar Sina , Jenkins Samir V. , Quick Charles M. , Griffin Robert J. , Dings Ruud P.M. , Rajaram Narasimhan , Barman Ishan 
Published: February 2019

Abstract

Delay in the assessment of tumor response to radiotherapy continues to pose a major challenge to quality of life for patients with nonresponsive tumors. Here, we exploited label-free Raman spectroscopic mapping to elucidate radiation-induced biomolecular changes in tumors and uncovered latent microenvironmental differences between treatment-resistant and -sensitive tumors. We used isogenic radiation-resistant and -sensitive A549 human lung cancer cells and human head and neck squamous cell carcinoma (HNSCC) cell lines (UM-SCC-47 and UM-SCC-22B, respectively) to grow tumor xenografts in athymic nude mice and demonstrated the molecular specificity and quantitative nature of Raman spectroscopic tissue assessments. Raman spectra obtained from untreated and treated tumors were subjected to chemometric analysis using multivariate curve resolution-alternating least squares (MCR-ALS) and support vector machine (SVM) to quantify biomolecular differences in the tumor microenvironment. The Raman measurements revealed significant and reliable differences in lipid and collagen content postradiation in the tumor microenvironment, with consistently greater changes observed in the radiation-sensitive tumors. In addition to accurately evaluating tumor response to therapy, the combination of Raman spectral markers potentially offers a route to predicting response in untreated tumors prior to commencing treatment. Combined with its noninvasive nature, our findings provide a rationale for in vivo studies using Raman spectroscopy, with the ultimate goal of clinical translation for patient stratification and guiding adaptation of radiotherapy during the course of treatment.

Significance:
These findings highlight the sensitivity of label-free Raman spectroscopy to changes induced by radiotherapy and indicate the potential to predict radiation resistance prior to commencing therapy.
Cumulative Psychosocial Stress and Ideal Cardiovascular Health in Older Women
Authors: Burroughs Peña Melissa S. , Mbassa Rachel S. , Slopen Natalie B. , Williams David R. , Buring Julie E. , Albert Michelle A. 
Published: February 2019

Background:
Research implicates acute and chronic stressors in racial/ethnic health disparities, but the joint impact of multiple stressors on racial/ethnic disparities in cardiovascular health is unknown.

Methods:
In 25 062 women (24 053 white; 256 Hispanic; 440 black; 313 Asian) articipating in the Women’s Health Study follow-up cohort, we examined the relationship between cumulative psychosocial stress (CPS) and ideal cardiovascular health (ICH), as defined by the American Heart Association’s 2020 strategic Impact Goals. This health metric includes smoking, body mass index, physical activity, diet, blood pressure, total cholesterol, and glucose, with higher levels indicating more ICH and less cardiovascular risk (score range, 0–7). We created a CPS score that summarized acute stressors (eg, negative life events) and chronic stressors (eg, work, work-family spillover, financial, discrimination, relationship, and neighborhood) and traumatic life event stress reported on a stress questionnaire administered in 2012 to 2013 (score range, 16–385, with higher scores indicating higher levels of stress).

Results:

White women had the lowest mean CPS scores (white: 161.7±50.4; Hispanic: 171.2±51.7; black: 172.5±54.9; Asian: 170.8±50.6;
P
overall
<0.01). Mean CPS scores remained higher in Hispanic, black, and Asian women than in white women after adjustment for age, socioeconomic status (income and education), and psychological status (depression and anxiety) (
P
<0.01 for each). Mean ICH scores varied by race/ethnicity (
P
<0.01) and were significantly lower in black women and higher in Asian women compared with white women (β-coefficient [95% CI]: Hispanics, −0.02 [−0.13 to −0.09]; blacks, −0.34 [−0.43 to −0.25]; Asians, 0.34 [0.24 to 0.45]); control for socioeconomic status and CPS did not change these results. Interactions between CPS and race/ethnicity in ICH models were not significant.

Conclusions:
Both CPS and ICH varied by race/ethnicity. ICH remained worse in blacks and better in Asians compared with whites, despite taking into account socioeconomic factors and CPS.
Abstract 294: Investigating the Small Heat Shock Proteins Impact on Aggregate Inhibition
Authors: Roth Andrew , Rye Hays 
Published: February 2019

The small heat shock proteins (sHsp) are a highly conserved protein chaperone family needed for ischemia/reperfusion recovery and mitigation of protein aggregation. Without them, environmental stressors, like hypoxia and oxidative stress, can cause highly toxic protein aggregation, leading to cardiomyopathy. Nevertheless, the mechanisms by which sHsps protect cell viability are poorly understood.
sHsp mechanism remains elusive due to their highly heterogeneous and dynamic nature making them difficult to study with current methods. To solve this problem, we use a single particle technique called Burst Analysis Spectroscopy (BAS). BAS provides a powerful approach, permitting the real-time observation of size population-resolved kinetics under non-perturbing, free solution conditions. This method allow us to observe events like protein aggregation as well as the interacting sHsp complexes.

To study the mechanism of aggregate inhibition by sHsps, we utilize the
E. coli
sHsps IbpA and IbpB (IbpAB) with two established protein substrates, RuBisCO from
R. Rubrum
and PepQ from
E. coli
. Prior work,
in vivo
and
in vitro
, has established that IbpAB play a similar role in
E. coli
as sHsp do in higher eukaryotes suggesting all sHsps may share common mechanistic properties.

Using BAS, we established PepQ and RuBisCO form large heterogeneous amorphous aggregates, with RuBisCO also capable of forming fibril-like aggregates under different aggregation conditions. When IbpAB are present during aggregation, both aggregate types decrease in size and form a very specific homogenous aggregate size distribution suggesting IbpAB activity is independent of protein aggregate substrate or structure. Remarkably, binding of IbpAB to RuBisCO aggregates differs dramatically depending on the aggregate structure. The amorphous aggregates appear to bind IbpAB at a RuBisCO monomer-to-IbpAB ratio of 1:1 while the fibril-like RuBisCO aggregates display a bifurcation, where two, distinct aggregate sub-populations bind IbpAB at very different stoichiometries. This data has uncovered the unknown capability of IbpAB/sHsps to inhibit ongoing aggregation of two substrates and structures through two different mechanistic processes all to the same homogenous aggregate size.
Contributions of Climatic Factors to Interannual Variability of the Vegetation Index in Northern China Grasslands
Authors: Zhao Wei , Hu Zhongmin , Guo Qun , Wu Genan , Chen Ruru , Li Shenggong 
Published: February 2019

AbstractUnderstanding the atmosphere–land surface interaction is crucial for clarifying the responses and feedbacks of terrestrial ecosystems to climate change. However, quantifying the effects of multiple climatic factors to vegetation activities is challenging. Using the geographical detector model (GDM), this study quantifies the relative contributions of climatic factors including precipitation, relative humidity, solar radiation, and air temperature to the interannual variation (IAV) of the normalized difference vegetation index (NDVI) in the northern grasslands of China during 2000 to 2016. The results show heterogeneous spatial patterns of determinant climatic factors on the IAV of NDVI. Precipitation and relative humidity jointly controlled the IAV of NDVI, illustrating more explanatory power than solar radiation and air temperature, and accounting for higher proportion of area as the determinant factor in the study region. It is noteworthy that relative humidity, a proxy of atmospheric aridity, is as important as precipitation for the IAV of NDVI. The contribution of climatic factors to the IAV of NDVI varied by vegetation type. Owing to the stronger explanatory power of climatic factors on NDVI variability in temperate grasslands, we conclude that climate variability may exert more influence on temperate grasslands than on alpine grasslands. Our study highlights the importance of the role of atmospheric aridity to vegetation activities in grasslands. We suggest focusing more on the differences between vegetation types when addressing the climate–vegetation relationships at a regional scale.