bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluid warming with parylene-coated enFlow cartridge: Bench and pilot animal study of aluminum extraction due to prolonged use
Authors: Waldmann Andreas D , Rose Edward A , Pedro Michael J
Published: June 2021

Objectives:

Intravenous fluid warming devices with surface heating systems transfer heat using aluminum blocks, which if uncoated elute toxic levels of aluminum into the infusate. This study examined extractable aluminum detected from prolonged use of the updated version of the enFlow® cartridge, which uses a parylene-coated aluminum heating block.

Methods:

In dynamic bench tests, we measured the concentration of aluminum that leached into three solutions (Sterofundin ISO, Plasma-Lyte 148, and whole blood) that were continuously pumped (0.2 and 5.5 mL min−1) and warmed to 40°C by the enFlow cartridge (parylene-coated) for 5 h. Prolonged quasi-static bench tests measured aluminum concentration in 16 solutions which were gently rocked within the enFlow cartridge (parylene-coated) for 72 h at 40°C. Aluminum concentrations were measured using inductively coupled mass spectroscopy and matrix blank corrected. Measured aluminum concentrations were compared to a Tolerable Exposure limit to calculate Margins of Safety based on the US Food and Drug Administration maximum recommended concentration in parenteral fluids (25 μg L−1). A parallel pilot in vivo animal study was performed using mice injected with fluids warmed for 72 h by the enFlow cartridge (parylene-coated).

Results:

The enFlow cartridge (parylene-coated) demonstrated low toxicological risks in all tests. Sterofundin ISO resulted in the highest aluminum concentration after simulated prolonged use of the enFlow cartridge (parylene-coated) (3.11 μg device−1), which represents a 99.2% decrease from the enFlow cartridge (uncoated) and Margin of Safety of 1.7. Dynamic tests at two different flow rates with three challenge solutions resulted in concentrations less than the method detection limits (20.6 or 41.2 μg L−1) of the analysis method. The animals in the in vivo study showed no evidence of toxicity.

Conclusion:

Observed toxicological risk levels associated with the enFlow cartridge (parylene-coated) intravenous fluid warmer were below those set by the Food and Drug Administration and suggest that the use of enFlow cartridge (parylene-coated) is safe with a variety of intravenous solution types and in different therapeutic scenarios.
Polyneuropathy: A Rare and Challenging Presentation of Essential Mixed Cryoglobulinemia
Authors: Taha Ahmed , Taha Mohamed , Ahmed Roaa , Meckler Gianna , Aeddula Narothama , Meckler Jason
Published: June 2021

A 49-year-old male presented with acute chronic sensory motor bilateral lower extremity polyneuropathy. Electromyography showed bilateral acute sensory motor axonal polyneuropathy. Lumbar spine magnetic resonance imaging showed diffuse bone marrow replacement and bilateral ankylosing spondylitis. Laboratory workup revealed elevated inflammatory markers and low G6PD (glucose-6-phosphate dehydrogenase) level. Due to elevated acute phase reactants, inflammatory polyneuropathy was suspected; patient was treated accordingly with resolution of neuropathy. Three months later, he relapsed and presented with disabling polyneuropathy and renal impairment, which prompted renal biopsy. Renal histopathology revealed the, otherwise mysterious, etiology, essential mixed cryoglobulinemia. Essential mixed cryoglobulinemia was not considered initially due to the absence of classic systemic manifestations of autoimmune disorders.
“This Happens in the Real World?”: Perceptions of Student-Developed Workplace Case Studies
Authors: Gettings Patricia E. , Meluch Andrea L.
Published: June 2021

This study examined student perceptions of an online case study development experience where students wrote their own case studies about workplace communication processes and created accompanying pedagogical materials. Students then shared their cases in small groups and engaged in dialogue. Students from organizational communication classes at four universities completed preevaluations ( n = 77) and postevaluations ( n = 67), providing quantitative and qualitative data. Analyses suggested that students perceived that the experience enhanced their understanding of course materials, aided them in connecting course materials to the real world, and enabled them to reflect on their own and their classmates’ organizational experiences.
Real-World Cost-Effectiveness of Bevacizumab With First-Line Combination Chemotherapy in Patients With Metastatic Colorectal Cancer: Population-Based Retrospective Cohort Studies in Three Canadian Provinces
Authors: Pataky Reka E. , Beca Jaclyn , Tran David , Dai Wei Fang , Dvorani Erind , Isaranuwatchai Wanrudee , Peacock Stuart , Alvi Riaz , Cheung Winson Y. , Earle Craig C. , Gavura Scott , Chan Kelvin K. W.
Published: June 2021

Background. Real-world evidence can be a valuable tool when clinical trial data are incomplete or uncertain. Bevacizumab was adopted as first-line therapy for metastatic colorectal cancer (mCRC) based on significant survival improvements in initial clinical trials; however, survival benefit diminished in subsequent analyses. Consequently, there is uncertainty surrounding the cost-effectiveness of bevacizumab therapy achieved in practice. Objective. To assess real-world cost-effectiveness of first-line bevacizumab with irinotecan-based chemotherapy versus irinotecan-based chemotherapy alone for mCRC in British Columbia (BC), Saskatchewan, and Ontario, Canada. Methods. Using provincial cancer registries and linked administrative databases, we identified mCRC patients who initiated publicly funded irinotecan-based chemotherapy, with or without bevacizumab, in 2000 to 2015. We compared bevacizumab-treated patients to historical controls (treated before bevacizumab funding) and contemporaneous controls (receiving chemotherapy without bevacizumab), using inverse-probability-of-treatment weighting with propensity scores to balance baseline covariates. We calculated incremental cost-effectiveness ratios (ICER) using 5-year cost and survival adjusted for censoring, with bootstrapping to characterize uncertainty. We also conducted one-way sensitivity analysis for key drivers of cost-effectiveness. Results. The cohorts included 12,112 (Ontario), 1,161 (Saskatchewan), and 2,977 (BC) patients. Bevacizumab significantly increased treatment costs, with mean ICERs between $78,000 and $84,000/LYG (life-year gained) in the contemporaneous comparisons and $75,000 and $101,000/LYG in the historical comparisons. Reducing the cost of bevacizumab by 50% brought ICERs in all comparisons below $61,000/LYG. Limitations. Residual confounding in observational data may bias results, while the use of original list prices overestimates current bevacizumab cost. Conclusion. The addition of bevacizumab to irinotecan-based chemotherapy extended survival for mCRC patients but at significant cost. At original list prices bevacizumab can only be considered cost-effective with certainty at a willingness-to-pay threshold over $100,000/LYG, but price reductions or discounts have a significant impact on cost-effectiveness.
Social Structures and Spatial Alignments of Agrarian Urbanisation
Authors: Sivaramakrishnan K.
Published: June 2021

Agrarian urbanisation has gathered pace and intensity in the last few decades after economic liberalisation in India. A faster rate of economic growth has exacerbated the extraction of rural natural resources to supply increased urban demands. At the same time, rural landscapes have been transformed by expanded infrastructure, new industrial ventures, conservation projects and urban sprawl. These processes have been mediated by shifting patterns of caste power and political mobilisation. However, they also seem to have exacerbated social inequality while making historically marginalised groups such as Dalits and Adivasis suffer greater dispossession and livelihood precarity. Case studies from different regions of India reveal both the socio-economic dynamics of regional variation in these broad outcomes of agrarian urbanism, and the cross-regional patterns of environmental degradation, exacerbated inequality and difficulties faced by agrarian society in reproducing itself as an integral part of Indian prosperity and progress.
The Role of Perceived Susceptibility and Collectivist Values in Support for Using Social Distancing to Prevent COVID-19 in the United States
Authors: Wang Xiao
Published: June 2021

The present investigation examined the factors that were related to U.S. residents’ support for social distancing measures (i.e., stay-at-home) that can help prevent COVID-19 infections and save lives. Relying on a survey of 387 U.S.-based participants from Amazon Mechanical Turk (MTurk), conducted in May 2020, the results revealed that perceived susceptibility and collectivist cultural values predicted their support for social distancing, both directly and indirectly. The total effect sizes were moderate and strong, respectively. In addition, instrumental attitudes were a stronger predictor of the participants’ support for social distancing than experiential attitudes and perceived behavioral control. The results contribute to the understanding of how risk perceptions, collectivist values, and various attitudes are related to an important preventive behavior (i.e., social distancing) during a pandemic. It should be acknowledged that the concept of social distancing evolved throughout the pandemic in the United States.
Benthic community establishment on different concrete mixtures introduced to a German deep-water port
Authors: Becker Lydia R. , Kröncke Ingrid , Ehrenberg Andreas , Feldrappe Volkert , Bischof Kai
Published: June 2021

Concrete is a widely used building material in coastal constructions worldwide. However, limited natural resources used in the production process, as well as high CO2-emission due to the calcination process of limestone and the thermal energy demand for Portland cement clinker production, raise the demand for alternative constituents. Alternative mixture types should be environmentally friendly and, at best, mimic natural hard substrates. Here five different concrete mixtures, containing different cements (Portland cement and blast furnace cements) and aggregates (sand, gravel, iron ore and metallurgical slags) were made. Three replicate cubes (15 × 15 × 15 cm) of each type were then deployed in a German deep-water Port, the JadeWeserPort, to study benthic community establishment after one year. Results are compared to a similar experiment conducted in a natural hard ground environment (Helgoland Island, Germany). Results indicate marked differences in settled communities in the Port site compared to natural environments. At the Port site community composition did not differ with the concrete mixtures. Surface orientation of the cubes (front/top/back) revealed significant differences in species abundances and compositions. Cubes hold more neobiota in the Port site than in natural hard ground environments. Implications for the usage of new concrete mixtures are discussed.
Caprine PRNP polymorphisms N146S and Q222K are associated with proteolytic cleavage of PrPC
Authors: Madsen-Bouterse Sally A. , Stewart Paula , Williamson Helen , Schneider David A. , Goldmann Wilfred
Published: June 2021

Expression of the cellular prion protein (PrPC) is crucial for the development of prion diseases. Amino acid changes in PrPC or a reduced amount of PrPC may modulate disease resistance. The relative abundance of C1, a natural α-cleavage fragment of PrPC, was previously found to be associated with a resistant PRNP genotype in sheep. Goats are another small ruminant where classical scrapie susceptibility is under strong genetic control. In this study, we assessed PrPC in goats for the existence of similar associations between PrPC fragments and genotype. Brain tissue homogenates from scrapie-free goats with wild type PRNP or polymorphisms (I142M, H143R, N146S, or Q222K) were deglycosylated prior to immunoblot for assessment of the relative abundance of the C1 fragment of PrPC. The presence of K222 or S146 alleles demonstrated significantly different relative levels of C1 compared to that observed in wild type goats, which suggests that the genotype association with C1 is neither unique to sheep nor exclusive to the ovine Q171R dimorphism.
ORFik: a comprehensive R toolkit for the analysis of translation
Authors: Tjeldnes Håkon , Labun Kornel , Torres Cleuren Yamila , Chyżyńska Katarzyna , Świrski Michał , Valen Eivind
Published: June 2021

Background

With the rapid growth in the use of high-throughput methods for characterizing translation and the continued expansion of multi-omics, there is a need for back-end functions and streamlined tools for processing, analyzing, and characterizing data produced by these assays.

Results

Here, we introduce ORFik, a user-friendly R/Bioconductor API and toolbox for studying translation and its regulation. It extends GenomicRanges from the genome to the transcriptome and implements a framework that integrates data from several sources. ORFik streamlines the steps to process, analyze, and visualize the different steps of translation with a particular focus on initiation and elongation. It accepts high-throughput sequencing data from ribosome profiling to quantify ribosome elongation or RCP-seq/TCP-seq to also quantify ribosome scanning. In addition, ORFik can use CAGE data to accurately determine 5′UTRs and RNA-seq for determining translation relative to RNA abundance. ORFik supports and calculates over 30 different translation-related features and metrics from the literature and can annotate translated regions such as proteins or upstream open reading frames (uORFs). As a use-case, we demonstrate using ORFik to rapidly annotate the dynamics of 5′ UTRs across different tissues, detect their uORFs, and characterize their scanning and translation in the downstream protein-coding regions.

Conclusion

In summary, ORFik introduces hundreds of tested, documented and optimized methods. ORFik is designed to be easily customizable, enabling users to create complete workflows from raw data to publication-ready figures for several types of sequencing data. Finally, by improving speed and scope of many core Bioconductor functions, ORFik offers enhancement benefiting the entire Bioconductor environment.

Availability

http://bioconductor.org/packages/ORFik.
Genetic differentiation in an endangered and strongly philopatric, migrant shorebird
Authors: Rönkä Nelli , Pakanen Veli-Matti , Pauliny Angela , Thomson Robert L. , Nuotio Kimmo , Pehlak Hannes , Thorup Ole , Lehikoinen Petteri , Rönkä Antti , Blomqvist Donald , Koivula Kari , Kvist Laura
Published: June 2021

Background

Populations living in fragmented habitats may suffer from loss of genetic variation and reduced between-patch dispersal, which are processes that can result in genetic differentiation. This occurs frequently in species with reduced mobility, whereas genetic differentiation is less common among mobile species such as migratory birds. The high dispersal capacity in the latter species usually allows for gene flow even in fragmented landscapes. However, strongly philopatric behaviour can reinforce relative isolation and the degree of genetic differentiation. The Southern Dunlin (Calidris alpina schinzii) is a philopatric, long-distance migratory shorebird and shows reduced dispersal between isolated breeding patches. The endangered population of the Southern Dunlin breeding at the Baltic Sea has suffered from habitat deterioration and fragmentation of coastal meadows. We sampled DNA across the entire population and used 12 polymorphic microsatellite loci to examine whether the environmental changes have resulted in genetic structuring and loss of variation.

Results

We found a pattern of isolation-by-distance across the whole Baltic population and genetic differentiation between local populations, even within the southern Baltic. Observed heterozygosity was lower than expected throughout the range and internal relatedness values were positive indicating inbreeding.

Conclusions

Our results provide long-term, empirical evidence for the theoretically expected links between habitat fragmentation, population subdivision, and gene flow. They also demonstrate a rare case of genetic differentiation between populations of a long-distance migratory species. The Baltic Southern Dunlin differs from many related shorebird species that show near panmixia, reflecting its philopatric life history and the reduced connectivity of its breeding patches. The results have important implications as they suggest that reduced connectivity of breeding habitats can threaten even long-distance migrants if they show strong philopatry during breeding. The Baltic Southern Dunlin warrants urgent conservation efforts that increase functional connectivity and gene flow between breeding areas.
Functional prediction of de novo uni-genes from chicken transcriptomic data following infectious bursal disease virus at 3-days post-infection
Authors: Azli Bahiyah , Ravi Sharanya , Hair-Bejo Mohd , Omar Abdul Rahman , Ideris Aini , Mat Isa Nurulfiza
Published: June 2021

Background

Infectious bursal disease (IBD) is an economically very important issue to the poultry industry and it is one of the major threats to the nation’s food security. The pathogen, a highly pathogenic strain of a very virulent IBD virus causes high mortality and immunosuppression in chickens. The importance of understanding the underlying genes that could combat this disease is now of global interest in order to control future outbreaks. We had looked at identified novel genes that could elucidate the pathogenicity of the virus following infection and at possible disease resistance genes present in chickens.

Results

A set of sequences retrieved from IBD virus-infected chickens that did not map to the chicken reference genome were de novo assembled, clustered and analysed. From six inbred chicken lines, we managed to assemble 10,828 uni-transcripts and screened 618 uni-transcripts which were the most significant sequences to known genes, as determined by BLASTX searches. Based on the differentially expressed genes (DEGs) analysis, 12 commonly upregulated and 18 downregulated uni-genes present in all six inbred lines were identified with false discovery rate of q-value < 0.05. Yet, only 9 upregulated and 13 downregulated uni-genes had BLAST hits against the Non-redundant and Swiss-Prot databases. The genome ontology enrichment keywords of these DEGs were associated with immune response, cell signalling and apoptosis. Consequently, the Weighted Gene Correlation Network Analysis R tool was used to predict the functional annotation of the remaining unknown uni-genes with no significant BLAST hits. Interestingly, the functions of the three upregulated uni-genes were predicted to be related to innate immune response, while the five downregulated uni-genes were predicted to be related to cell surface functions. These results further elucidated and supported the current molecular knowledge regarding the pathophysiology of chicken’s bursal infected with IBDV.

Conclusion

Our data revealed the commonly up- and downregulated novel uni-genes identified to be immune- and extracellular binding-related, respectively. Besides, these novel findings are valuable contributions in improving the current existing integrative chicken transcriptomics annotation and may pave a path towards the control of viral particles especially towards the suppression of IBD and other infectious diseases in chickens.
Brain size reductions associated with endothelin B receptor mutation, a cause of Hirschsprung’s disease
Authors: Chen Ko-Chin , Song Zan-Min , Croaker Geoffrey D.
Published: June 2021

Background

ETBhas been reported to regulate neurogenesis and vasoregulation in foetal development. Its dysfunction was known to cause HSCR, an aganglionic colonic disorder with syndromic forms reported to associate with both small heads and developmental delay. We therefore asked, "is CNS maldevelopment a more general feature of ETBmutation?" To investigate, we reviewed the micro-CT scans of an ETB−/−model animal,sl/slrat, and quantitatively evaluated the structural changes of its brain constituents.

Methods

Eleven neonatal rats generated from ETB+/−cross breeding were sacrificed. Micro-CT scans were completed following 1.5% iodine-staining protocols. All scans were reviewed for morphological changes. Selected organs were segmented semi-automatically post-NLM filtering: TBr, T-CC, T-CP, OB, Med, Cer, Pit, and S&I Col. Volumetric measurements were made using Drishti rendering software. Rat genotyping was completed following analysis. Statistical comparisons on organ volume, organ growth rate, and organ volume/bodyweight ratios were made betweensl/sland the control groups based on autosomal recessive inheritance. One-way ANOVA was also performed to evaluate potential dose-dependent effect.

Results

sl/slrat has 16.32% lower body weight with 3.53% lower growth rate than the control group. Gross intracranial morphology was preserved insl/slrats. However, significant volumetric reduction of 20.33% was detected in TBr; similar reductions were extended to the measurements of T-CC, T-CP, OB, Med, and Pit. Consistently, lower brain and selected constituent growth rates were detected insl/slrat, ranging from 6.21% to 11.51% reduction. Lower organ volume/bodyweight ratio was detected insl/slrats, reflecting disproportional neural changes with respect to body size. No consistent linear relationships exist between ETBcopies and intracranial organ size or growth rates.

Conclusion

Although ETB−/−mutant has a normal CNS morphology, significant size reductions in brain and constituents were detected. These structural changes likely arise from a combination of factors secondary to dysfunctional ET-1/ET-3/ETBsignalling, including global growth impairment from HSCR-induced malnutrition and dysregulations in the neurogenesis, angiogenesis, and cerebral vascular control. These changes have important clinical implications, such as autonomic dysfunction or intellectual delay. Although further human study is warranted, our study suggested comprehensive managements are required for HSCR patients, at least in ETB−/−subtype.
Combining QTL-seq and linkage mapping to fine map a candidate gene in qCTS6 for cold tolerance at the seedling stage in rice
Authors: Yang Luomiao , Wang Jingguo , Han Zhenghong , Lei Lei , Liu Hua Long , Zheng Hongliang , Xin Wei , Zou Detang
Published: June 2021

Background

Cold stress caused by low temperatures is an important factor restricting rice production. Identification of cold-tolerance genes that can stably express in cold environments is crucial for molecular rice breeding.

Results

In this study, we employed high-throughput quantitative trait locus sequencing (QTL-seq) analyses in a 460-individual F2:3mapping population to identify major QTL genomic regions governing cold tolerance at the seedling stage in rice. A novel major QTL (qCTS6) controlling the survival rate (SR) under low-temperature conditions of 9°C/10 days was mapped on the 2.60-Mb interval on chromosome 6. Twenty-seven single-nucleotide polymorphism (SNP) markers were designed for theqCST6region based on re-sequencing data, and local QTL mapping was conducted using traditional linkage analysis. Eventually, we mappedqCTS6to a 96.6-kb region containing 13 annotated genes, of which seven predicted genes contained 13 non-synonymous SNP loci. Quantitative reverse transcription PCR analysis revealed that only Os06g0719500, anOsbZIP54transcription factor, was strongly induced by cold stress. Haplotype analysis confirmed that +376 bp (T>A) in theOsbZIP54coding region played a key role in regulating cold tolerance in rice.

Conclusion

We identifiedOsbZIP54as a novel regulatory gene associated with rice cold-responsive traits, with its Dongfu-104 allele showing specific cold-induction expression serving as an important molecular variation for rice improvement. This result is expected to further exploration of the genetic mechanism of rice cold tolerance at the seedling stage and improve cold tolerance in rice varieties by marker-assisted selection.
Clinical findings of Talaromyces marneffei infection among patients with anti-interferon-γ immunodeficiency: a prospective cohort study
Authors: Chen Zhao-Ming , Li Zheng-Tu , Li Shao-Qiang , Guan Wei-Jie , Qiu Ye , Lei Zi-Ying , Zhan Yang-Qing , Zhou Hua , Lin Sheng , Wang Xinni , Li Zhun , Yang Feng , Zeng Wen , Lin Ye , Liu Jing , Zhang Jian-Quan , Ye Feng
Published: June 2021

Background

Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China.

Methods

Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded.

Results

Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy.

Conclusion

T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.
Automated left atrial time-resolved segmentation in MRI long-axis cine images using active contours
Authors: Gonzales Ricardo A. , Seemann Felicia , Lamy Jérôme , Arvidsson Per M. , Heiberg Einar , Murray Victor , Peters Dana C.
Published: June 2021

Background

Segmentation of the left atrium (LA) is required to evaluate atrial size and function, which are important imaging biomarkers for a wide range of cardiovascular conditions, such as atrial fibrillation, stroke, and diastolic dysfunction. LA segmentations are currently being performed manually, which is time-consuming and observer-dependent.

Methods

This study presents an automated image processing algorithm for time-resolved LA segmentation in cardiac magnetic resonance imaging (MRI) long-axis cine images of the 2-chamber (2ch) and 4-chamber (4ch) views using active contours. The proposed algorithm combines mitral valve tracking, automated threshold calculation, edge detection on a radially resampled image, edge tracking based on Dijkstra’s algorithm, and post-processing involving smoothing and interpolation. The algorithm was evaluated in 37 patients diagnosed mainly with paroxysmal atrial fibrillation. Segmentation accuracy was assessed using the Dice similarity coefficient (DSC) and Hausdorff distance (HD), with manual segmentations in all time frames as the reference standard. For inter-observer variability analysis, a second observer performed manual segmentations at end-diastole and end-systole on all subjects.

Results

The proposed automated method achieved high performance in segmenting the LA in long-axis cine sequences, with a DSC of 0.96 for 2ch and 0.95 for 4ch, and an HD of 5.5 mm for 2ch and 6.4 mm for 4ch. The manual inter-observer variability analysis had an average DSC of 0.95 and an average HD of 4.9 mm.

Conclusion

The proposed automated method achieved performance on par with human experts analyzing MRI images for evaluation of atrial size and function.
Risks associated with continuation of potentially inappropriate antihypertensive medications in older adults receiving hemodialysis
Authors: Hall Rasheeda K. , Morton Sarah , Wilson Jonathan , Ephraim Patti L. , Boulware L. Ebony , St. Peter Wendy L. , Colón-Emeric Cathleen , Pendergast Jane , Scialla Julia J.
Published: June 2021

Background and objectives

After dialysis initiation, older adults may experience orthostatic or post-dialysis hypotension. Some orthostasis-causing antihypertensives (i.e., central alpha agonists and alpha blockers), are considered potentially inappropriate medications (PIMs) for older adults because they carry more risk than benefit. We sought to (1) describe antihypertensive PIM prescribing patterns before and after dialysis initiation and (2) ascertain the potential risk of adverse outcomes when these medications are continued after dialysis initiation.

Design, setting, participants, and measurements

Using United States Renal Data System data, we evaluated monthly prevalence of antihypertensive PIM claims in the period before and after dialysis initiation among older adults aged ≥66 years initiating in-center hemodialysis in the US between 2013 and 2014. Patients with an antihypertensive PIM prescription at hemodialysis initiation and who survived for 120 days were classified as ‘continuers’ or ‘discontinuers’ based on presence or absence of a refill within the 120 days after initiation. We compared rates of hospitalization and risk of death across these groups from day 121 through 24 months after dialysis initiation.

Results

Our study included 30,760 total patients, of whom 5981 (19%) patients had an antihypertensive PIM claim at dialysis initiation and survived ≥120 days. Most [65% (n = 3920)] were continuers. Those who continued (versus discontinued) were more likely to be black race (26% versus 21%), have dual Medicare-Medicaid coverage (31% versus 27%), have more medications on average (12 versus 9) and have no functional limitations (84% versus 80%). Continuers experienced fewer all-cause hospitalizations and deaths, but neither were statistically significant after adjustment (Hospitalization: RR 0.93, 95% CI 0.86, 1.00; Death: HR 0.89, 95% CI: 0.78–1.02).

Conclusions

Nearly one in five older adults had an antihypertensive PIM at dialysis initiation. Among those who survived ≥120 days, continuation of an antihypertensive PIM was not associated with increased risk of all-cause hospitalization or mortality.
A stemness-based eleven-gene signature correlates with the clinical outcome of hepatocellular carcinoma
Authors: Hong Liang , Zhou Yu , Xie Xiangbang , Wu Wanrui , Shi Changsheng , Lin Heping , Shi Zhenjing
Published: June 2021

Background

Cumulative evidences have been implicated cancer stem cells in the tumor environment of hepatocellular carcinoma (HCC) cells, whereas the biological functions and prognostic significance of stemness related genes (SRGs) in HCC is still unclear.

Methods

Molecular subtypes were identified by cumulative distribution function (CDF) clustering on 207 prognostic SRGs. The overall survival (OS) predictive gene signature was developed, internally and externally validated based on HCC datasets including The Cancer Genome Atlas (TCGA), GEO and ICGC datasets. Hub genes were identified in molecular subtypes by protein-protein interaction (PPI) network analysis, and then enrolled for determination of prognostic genes. Univariate, LASSO and multivariate Cox regression analyses were performed to assess prognostic genes and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC) curve, Kaplan-Meier curve and nomogram were used to assess the performance of the gene signature.

Results

We identified four molecular subtypes, among which the C2 subtype showed the highest SRGs expression levels and proportions of immune cells, whereas the worst OS; the C1 subtype showed the lowest SRGs expression levels and was associated with most favorable OS. Next, we identified 11 prognostic genes (CDX2, PON1, ADH4, RBP2, LCAT, GAL, LPA, CYP19A1, GAST, SST and UGT1A8) and then constructed a prognostic 11-gene module and validated its robustness in all three datasets. Moreover, by univariate and multivariate Cox regression, we confirmed the independent prognostic ability of the 11-gene module for patients with HCC. In addition, calibration analysis plots indicated the excellent predictive performance of the prognostic nomogram constructed based on the 11-gene signature.

Conclusions

Findings in the present study shed new light on the role of stemness related genes within HCC, and the established 11-SRG signature can be utilized as a novel prognostic marker for survival prognostication in patients with HCC.
Viral hepatitis associated hepatocellular carcinoma on the African continent, the past, present, and future: a systematic review
Authors: Dakurah Ottovon Bismark , Tamandjou Cynthia Raissa Tchuem , Zunza Moleen , Preiser Wolfgang , Maponga Tongai Gibson
Published: June 2021

Background

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in Africa. In Africa, the major causes of HCC include chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Knowledge of the changes in the incidence of viral hepatitis-associated HCC over time and the factors responsible for such changes is key in informing policies for the prevention of viral hepatitis-associated HCC in Africa.

Aim

The study aimed to systematically summarize the changes in the prevalence of viral hepatitis among HCC patients and the overall effect of the prevalence of viral hepatitis on the incidence of HCC over the past four decades in Africa (1980–2019).

Methods

A literature search was conducted in MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Web of Science, and African wide web for articles published on viral hepatitis-associated HCC in Africa from 1980 to 2019. The abstracts of the articles were screened for eligibility and those meeting the inclusion criteria were retrieved and reviewed.

Results

A total of 272 studies were included in the analysis. Viral hepatitis-related HCC incidence changed by 1.17% (95% confidence interval (CI): 0.63–1.71, p < 0.001), 0.82% (95% CI: 0.45–1.18, p < 0.001), and 3.34% (95% CI: 2.44–4.25, p < 0.001) for every 1% change in the prevalence of HBV, HCV, and hepatitis D virus (HDV) respectively, per decade. The incidence of HBV-related HCC decreased by − 0.50% (95% CI: − 0.74 – − 0.25, p < 0.001) over the last 40 years, while HCV-related HCC increased.

Conclusion

Overall, the incidence of viral hepatitis-associated HCC has not declined, mainly due to no decline in the prevalence of HCV, HDV, and the high number of chronic hepatitis B carriers on the African continent. There is an urgent need for the allocation of resources for the implementation of treatment and preventive programs for HBV, HCV, HDV, and HCC in Africa.

This systematic review is registered with PROSPERO®, number CRD42020169723.
Local treatment for triple-negative breast cancer patients undergoing chemotherapy: breast-conserving surgery or total mastectomy?
Authors: Guo Leqian , Xie Guilan , Wang Ruiqi , Yang Liren , Sun Landi , Xu Mengmeng , Yang Wenfang , Chung Mei Chun
Published: June 2021

Background

Because there is no exact therapeutic target, the systemic treatment of triple-negative breast cancer (TNBC) still relies on chemotherapy. In terms of local treatment, based on the highly malignant characteristics of TNBC, it is still uncertain whether patients should be given more aggressive local treatment.

Methods

This study was based on the SEER database. 13,262 TNBC patients undergoing chemotherapy were included. According to local treatment methods, patients were divided into breast-conserving surgery with radiotherapy (BCS + RT), total mastectomy alone and total mastectomy with radiotherapy (Mastectomy+RT). Kaplan-Meier survival analysis drew the survival curves of Overall Survival (OS) and Breast Cancer Specific Survival (BCSS), and Cox proportional risk regression models were used to analyze the impact of different local treatments on OS and BCSS.

Results

After adjusting confounding factors, Mastectomy alone group (HR = 1.57; 95%CI: 1.40–1.77) and Mastectomy+RT group (HR = 1.28; 95%CI: 1.12–1.46) were worse in OS than BCS + RT group, and Mastectomy+RT group (HR = 0.81; 95%CI: 0.73–0.91) was better in OS than Mastectomy alone group. The effect of local treatment for BCSS was similar to that of OS. After stratification according to age, tumor size and lymph node status, when the age was less than 55 years old, at T4, N2 or N3 category, there was no statistical significance between the BCS + RT group and the Mastectomy+RT group in OS or BCSS (allP > 0.05). When the age was less than 65 years old, at T1, T2 or N0 category, there was no statistical significance between the Mastectomy alone group and the Mastectomy+RT group in OS or BCSS (allP > 0.05). The results of other stratified analyses were basically consistent with the results of total population analysis.

Conclusion

The survival benefit of breast-conserving surgery with radiotherapy was higher than or similar to that of total mastectomy TNBC patients.
A qualitative study of stakeholder views on the use of a digital app for supported self-management in early intervention services for psychosis
Authors: Steare Thomas , Giorgalli Maria , Free Katherine , Harju-Seppänen Jasmine , Akther Syeda , Eskinazi Michelle , O’Hanlon Puffin , Rostill Helen , Amani Sarah , Lloyd-Evans Brynmor , Osborn David , Johnson Sonia
Published: June 2021

Background

Digital tools such as Smartphones have the potential to increase access to mental health support including self-management interventions for individuals with psychosis, and ultimately to improve outcomes. Self-management strategies, including relapse prevention and crisis planning and setting personal recovery goals, are intended to assist people with long-term conditions to take an active role in their recovery, with evidence for a range of benefits. However, their implementation is inconsistent, and access and uptake need to be improved. The current study explores the acceptability of a Smartphone app (My Journey 3) that has been developed to facilitate supported self-management in Early Intervention in Psychosis (EIP) services.

Methods

Semi-structured one-to-one interviews were conducted with twenty-one EIP service users who had access to My Journey 3 as part of a feasibility trial, and with thirteen EIP service clinicians who were supporting service users with the app. Interviews focused on the acceptability and usability of My Journey 3. Data was coded to themes based on the Acceptability of Healthcare Interventions framework.

Results

Many service user participants found My Journey 3 to be acceptable. The symptom and medication trackers in particular were described as helpful. A smaller number of service users disliked the intervention. Individual-level factors that appeared to influence acceptability and engagement included recovery stage and symptom severity. Clinicians tended to report that My Journey 3 was a potentially positive addition to service users’ care, but they often felt unable to provide support due to competing demands in their work, which in turn may have impacted acceptability and usage of the app.

Conclusions

Our findings suggest that the app is perceived as having potential to improve users’ capacity to self-manage and work towards recovery goals, but barriers prevented many clinicians providing consistent and effective support as intended. Further evaluation of supported self-management apps in psychosis is warranted but needs to address implementation challenges from the start.
Do psychological factors affect outcomes in musculoskeletal shoulder disorders? A systematic review
Authors: Sheikhzadeh Ali , Wertli Maria M. , Weiner Shira Schecter , Rasmussen-Barr Eva , Weiser Sherri
Published: June 2021

Background

Psychological factors may impact recovery in patients undergoing treatment for shoulder complaints. The aim of this review is to systematically analyse the evidence for the effect of modifiable psychological factors (MPF) on outcome, for patients with musculoskeletal shoulder disorders undergoing conservative or surgical treatment. MPF refers to factors that may change with intervention.

Methods

This is a systematic literature review. Five databases searched (MEDLINE, CINAHL, Cochrane Library, Embase and PsycInfo), for longitudinal studies investigating the influence of MPF on prognosis of patients with shoulder disorders, all diagnoses, undergoing clinical interventions (conservative or surgical). Level of evidence was determined using Scottish Intercollegiate Guidelines Network (SIGN) methodology. Moderate and high quality evidence was included. We extracted all MPF, categorized constructs into the following domains: beliefs (self-efficacy, expectation of recovery), coping (catastrophizing, avoidant coping), and affect (depression, anxiety). We evaluated constructs for its predictive value of at least one outcome. Outcomes were informed by this review. Evidence was classified into three categories: evidence for, inconclusive evidence, and evidence against.

Results

Of 1170 references, 40 distinct publications based on 35 datasets were included (intervention type: 20 surgical; 20 conservative). Overall, 22 studies (20 cohort studies and 2 RCTs) were classified as high quality and 18 studies (16 cohort studies, 2 RCTs) were classified as moderate quality. Outcomes reported included pain, disability/function, perceived recovery, physical and mental health, and work status. Based on the review, of the psychological constructs explored, these data would suggest that expectation of recovery, catastrophizing, avoidant coping, depression, and anxiety may predict outcome for patients managed surgically. In patients undergoing conservative intervention the evidence was either against (catastrophizing, depression, anxiety) or inconclusive (self-efficacy, expectation of recovery, avoidant coping) for the predictive value of psychological factors on outcome.

Conclusions

Five constructs were predictive of outcome for surgically managed patients. This suggests that implementing the biopsychosocial approach (i.e., preoperative screening, intervention by a trained clinician) may be advantageous for patients recommended for shoulder surgery,,. The same is not indicated for conservatively managed patients as no conclusive association of MPF with outcomes was noted. The importance of other MPF on outcome requires further investigation.
The incidence of distal radius fractures in a Swedish pediatric population - an observational cohort study of 90 970 individual fractures
Authors: Südow Hanna , Navarro Cecilia Mellstrand
Published: June 2021

Background

40–50 % of all boys and 30–40 % of girls suffer from at least one fracture during childhood. A quarter of these fractures affects the wrist, making it the worst affected part of the body. Children often sustain the injury during play or sport activities. There has been a lifestyle change among European children during the last decades, and there is reason to believe that fracture incidence is changing.

Methods

For the purpose of this observational cohort study registry data was retrieved from the Swedish National Patient Register for all pediatric patients registered with a distal radius fracture during the period 2005–2013. Incidence rates were calculated for each year using data from Statistic Sweden on population size by age and gender.

Results

90 970 distal radius fractures were identified. The mean age at the time of fracture was 10 years. In ages 10–17 the proportion of male patients was significantly larger. Seasonal variations were detected with peak incidences in May and September. A decreasing total fracture incidence was observed during the study period.

Conclusions

The incidence of distal radius fractures in a population 0–17 years in Sweden was higher among male than in female patients. The incidence was lower in 2008–2013 as compared to 2005. Further studies are necessary to reveal if the incidence will continue to decrease.
Physical therapy for patients with low back pain in Germany: a survey of current practice
Authors: Bahns Carolin , Happe Lisa , Thiel Christian , Kopkow Christian
Published: June 2021

Background

Low back pain (LBP) is one of the most common musculoskeletal disorders worldwide. The National Disease Management Guideline (NVL) “Non-specific LBP” is a practical decision-making aid for both physicians and non-medical professionals in Germany to improve quality of health care. Although LBP is the most frequent diagnosis resulting in physical therapy treatment, information on the current management of patients with LBP and guideline adherence is limited. The objective of this study was to evaluate the current physical therapy management of patients with LBP in Germany, and to explore guideline adherence to the NVL “Non-specific LBP” recommendations.

Methods

An online survey among physical therapists working in Germany was conducted based on the recommendations given in the NVL “Non-specific LBP”. Participants were recruited using a snowball sampling approach and invited to complete the questionnaire. Guideline adherence was evaluated by comparing the survey findings with the recommendations of the NVL.

Results

In total, 1361 physical therapists (41 years of age (SD 11); 839 female, 514 male; 16 years of clinical experience (SD 10)) completed the survey.

Fifty percent (n = 675) of our respondents adhered to the recommendations of the NVL on the therapeutic diagnostic process, and 72% (n = 973) to the recommendations concerning treatment. The guideline adherence across the entire management process (i.e., both diagnosis and treatment) of LBP was 38% (n = 513). German physical therapists predominantly provide active interventions, e.g., exercise therapy, but also use interventions with low or conflicting evidence, respectively. Massage and Kinesio Taping were frequently used despite being not recommended. Less than one third of study participants (n = 400, 29%) answered to know the NVL or had dealt with its recommendations.

Conclusions

In the management of LBP, overall guideline adherence among German physical therapists was 38% with higher adherence in the treatment section than in the physical therapeutic diagnostic process. Widespread employment of implementation strategies and removal of existing barriers against the application of evidence-based guidelines could facilitate the transfer of scientific evidence into clinical practice and contribute to optimize the quality of health care.

Trial registration

German Clinical Trials Register (DRKS00012607). Registered 04 October 2017.
Multivariate analysis of the relationship between gluteal muscle contracture and coxa valga
Authors: Zhang Yi , Su Qihang , Zhang Yuanzhen , Ge Heng’an , Wei Wang , Cheng Biao
Published: June 2021

Background

Gluteal muscle contracture (GMC) is a disease characterized by the limited function of the hip joint, knee pain, and abnormal gait. There is a lack of research on the effect of GMC on the hip joint structure to date. This study aims to analyze the association between GMC and the deformity of the hip and pelvis.

Methods

Standing anteroposterior pelvic radiographs of 214 patients (152 with gluteal muscle contracture and 62 without gluteal muscle contracture) were retrospectively collected. Neck–shaft angle, lateral center edge angle, Tönnis angle, femoral head coverage index, acetabular depth, Sacro-femoral-pubic angle, and obturator foramen ratio were respectively measured and included in the following statistical analysis. The collected data were analyzed using logistical regression and multiple linear regression to explore the factors influencing coxa valga and SFP angle.

Results

GMC was identified as a common factor significantly associated with coxa valga and increased SFP angle. There is a difference of risk factors in logistic regression for coxa valga between the left and right sides.

Conclusion

GMC is a significant risk factor for coxa valga and increased SFP angle. Given that GMC can cause coxa valga and likely alter the pelvis’s position, GMC should be paid attention to and treated early.