bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of HIV infection on tuberculosis transmission in a country with low tuberculosis incidence: a national retrospective study using molecular epidemiology
Authors: Winter Joanne R. , Smith Colette J. , Davidson Jennifer A. , Lalor Maeve K. , Delpech Valerie , Abubakar Ibrahim , Stagg Helen R.
Published: December 2020

Background

HIV is known to increase the likelihood of reactivation of latent tuberculosis to active TB disease; however, its impact on tuberculosis infectiousness and consequent transmission is unclear, particularly in low-incidence settings.

Methods

National surveillance data from England, Wales and Northern Ireland on tuberculosis cases in adults from 2010 to 2014, strain typed using 24-locus mycobacterial-interspersed-repetitive-units–variable-number-tandem-repeats was used retrospectively to identify clusters of tuberculosis cases, subdivided into ‘first’ and ‘subsequent’ cases.

Firstly, we used zero-inflated Poisson regression models to examine the association between HIV status and the number of subsequent clustered cases (a surrogate for tuberculosis infectiousness) in a strain type cluster. Secondly, we used logistic regression to examine the association between HIV status and the likelihood of being a subsequent case in a cluster (a surrogate for recent acquisition of tuberculosis infection) compared to the first case or a non-clustered case (a surrogate for reactivation of latent infection).

Results

We included 18,864 strain-typed cases, 2238 were the first cases of clusters and 8471 were subsequent cases. Seven hundred and fifty-nine (4%) were HIV-positive.

Outcome 1: HIV-positive pulmonary tuberculosis cases who were the first in a cluster had fewer subsequent cases associated with them (mean 0.6, multivariable incidence rate ratio [IRR] 0.75 [0.65–0.86]) than those HIV-negative (mean 1.1).

Extra-pulmonary tuberculosis (EPTB) cases with HIV were less likely to be the first case in a cluster compared to HIV-negative EPTB cases. EPTB cases who were the first case had a higher mean number of subsequent cases (mean 2.5, IRR (3.62 [3.12–4.19]) than those HIV-negative (mean 0.6).

Outcome 2: tuberculosis cases with HIV co-infection were less likely to be a subsequent case in a cluster (odds ratio 0.82 [0.69–0.98]), compared to being the first or a non-clustered case.

Conclusions

Outcome 1: pulmonary tuberculosis-HIV patients were less infectious than those without HIV. EPTB patients with HIV who were the first case in a cluster had a higher number of subsequent cases and thus may be markers of other undetected cases, discoverable by contact investigations.

Outcome 2: tuberculosis in HIV-positive individuals was more likely due to reactivation than recent infection, compared to those who were HIV-negative.
Blood leukocyte composition and function in periparturient ewes kept on different dietary magnesium supply
Authors: Ahmed Mona H. , Wilkens Mirja R. , Möller Bernd , Ganter Martin , Breves Gerhard , Schuberth Hans-Joachim
Published: December 2020

Background

Transition period (TP) is characterised by physiological and metabolic changes contributing to immunodysregulation. Since knowledge about this period in sheep is scarce, we analysed changes in selected immune variables during the TP in ewes and whether dietary magnesium (Mg) supplementation could modulate these immune variables. Pregnant ewes (2nd and 3rd lactation) were divided into a control group (CONT, n = 9) and a Mg group (MAG, n = 10) supplemented with Mg oxide resulting in a daily Mg intake of approximately 0.30 and 0.38% (MAG) of dry matter during ante- (a.p.) and post-partum (p.p.) periods, respectively. Blood samples were collected between days (d) 30 a.p. and d 30 p.p.. Whole blood neutrophil phagocytic activity, monocyte subset (classical cM, intermediate intM, non-classical ncM) composition and the proliferative capacity of lymphocytes were determined flow cytometrically. At d 14 a.p., all ewes were vaccinated against Mycobacterium avium subsp. paratuberculosis (MAP).

Results

Both groups showed a sharp increase in the total leukocyte counts (TLC) and neutrophil counts (P < 0.0001), at d 1 p.p., while, monocytes and their subpopulations displayed the highest values at d 30 p.p. (P ≤ 0.05). At d 1 p.p. the neutrophil phagocytic activity was higher (P < 0.05) in MAG ewes. Throughout the TP, the proliferative response of CD4+ cells was significantly higher in the MAG group (P < 0.05). Ewes in both groups responded with an increase in the TLC, neutrophil numbers (P ≤ 0.05) and ncM (P < 0.001) 24 h post vaccination, whereas monocytes and cM dropped in numbers (P ≤ 0.05). Numbers of intM only increased in MAG ewes (P < 0.05), whereas lymphocyte numbers decreased (P < 0.01). Mg supplementation did not affect the significant increase in MAP-specific antibodies at d 7 and 21 post vaccination. Total Mg and Ca serum levels did not show any differences between the two groups.

Conclusion

Whereas TP-associated fluctuations in blood leukocyte numbers are not influenced by Mg supplementation, neutrophil phagocytic activity, the proliferative capacity of CD4+ cells and the cellular response within 24 h after a vaccination are subject to modulation.
Manipulating the position of DNA expression cassettes using location tags fused to dCas9 (Cas9-Lag) to improve metabolic pathway efficiency
Authors: Xie Qianwen , Li Siwei , Zhao Dongdong , Ye Lijun , Li Qingyan , Zhang Xueli , Zhu Li , Bi Changhao
Published: December 2020

Background

Deactivated Cas9 (dCas9) led to significant improvement of CRISPR/Cas9-based techniques because it can be fused with a variety of functional groups to form diverse molecular devices, which can manipulate or modify target DNA cassettes. One important metabolic engineering strategy is to localize the enzymes in proximity of their substrates for improved catalytic efficiency. In this work, we developed a novel molecular device to manipulate the cellular location of specific DNA cassettes either on plasmids or on the chromosome, by fusing location tags to dCas9 (Cas9-Lag), and applied the technique for synthetic biology applications. Carotenoids like β-carotene serve as common intermediates for the synthesis of derivative compounds, which are hydrophobic and usually accumulate in the membrane compartment.

Results

Carotenoids like β-carotene serve as common intermediates for the synthesis of derivative compounds, which are hydrophobic and usually accumulate in the membrane components. To improve the functional expression of membrane-bound enzymes and localize them in proximity to the substrates, Cas9-Lag was used to pull plasmids or chromosomal DNA expressing carotenoid enzymes onto the cell membrane. For this purpose, dCas9 was fused to the E. coli membrane docking tag GlpF, and gRNA was designed to direct this fusion protein to the DNA expression cassettes. With Cas9-Lag, the zeaxanthin and astaxanthin titer increased by 29.0% and 26.7% respectively. Due to experimental limitations, the electron microscopy images of cells expressing Cas9-Lag vaguely indicated that GlpF-Cas9 might have pulled the target DNA cassettes in close proximity to membrane. Similarly, protein mass spectrometry analysis of membrane proteins suggested an increased expression of carotenoid-converting enzymes in the membrane components.

Conclusion

This work therefore provides a novel molecular device, Cas9-Lag, which was proved to increase zeaxanthin and astaxanthin production and might be used to manipulate DNA cassette location.
RETRACTED ARTICLE: GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway
Authors: Chen Hong , Xu Lu , Shan Zhi-li , Chen Shu , Hu Hao
Published: December 2020

Background

Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported.

Methods

Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohistochemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot.

Results

The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the proliferation, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes.

Conclusions

These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.
Musashi-1 promotes cancer stem cell properties of glioblastoma cells via upregulation of YTHDF1
Authors: Yarmishyn Aliaksandr A. , Yang Yi-Ping , Lu Kai-Hsi , Chen Yi-Chen , Chien Yueh , Chou Shih-Jie , Tsai Ping-Hsing , Ma Hsin-I. , Chien Chian-Shiu , Chen Ming-Teh , Wang Mong-Lien
Published: December 2020

Background

Glioblastoma (GBM) is the most lethal brain tumor characterized by high morbidity and limited treatment options. Tumor malignancy is usually associated with the epigenetic marks, which coordinate gene expression to ascertain relevant phenotypes. One of such marks is m6A modification of RNA, whose functional effects are dependent on the YTH family m6A reader proteins.

Methods and results

In this study, we investigated the expression of five
YTH family proteins in different GBM microarray datasets from the Oncomine
database, and identified YTHDF1 as the most highly overexpressed member of this
family in GBM. By performing the knockdown of YTHDF1 in a GBM cell line, we
found that it positively regulates proliferation, chemoresistance and cancer
stem cell-like properties. Musashi-1 (MSI1) is a postranscriptional gene
expression regulator associated with high oncogenicity in GBM. By knocking down
and overexpressing MSI1, we found that it positively regulates YTHDF1
expression. The inhibitory effects
imposed on the processes of proliferation and migration by YTHDF1 knockdown
were shown to be partially rescued by concomitant overexpression of MSI1. MSI1
and YTHDF1 were shown to be positively correlated in clinical glioma samples,
and their concomitant upregulation was associated with decreased survival of
glioma patients. We identified the direct regulation of YTHDF1 by MSI1.

Conclusions

Given the fact that both proteins are master
regulators of gene expression, and both of them are unfavorable factors in GBM,
we suggest that in any future studies aimed to uncover the prognostic value and
therapy potential, these two proteins should be considered together.
Antimicrobial coating is associated with significantly lower aerobic colony counts in high-touch areas in an orthopedic ward environment
Authors: Ejerhed Lars , Roshani Leyla , Andersson Annette Erichsen
Published: December 2020

Background

Hospital acquired infections (HAI) are the most common complication found in the hospital environment. The aim of the study was to examine whether the use of an antimicrobial coating in high-touch areas in an orthopedic ward could reduce bacterial growth and HAI.

Methods

From December 2017 to February 2018, HAI were registered on two orthopedic wards. A second registration was performed from December 2018 to February 2019. On the second occasion, an antimicrobial organosilane coating was applied just before the study period and thereafter weekly on one ward, while the other ward served as a control. Twenty defined high-touch areas on each ward were cultured before treatment and after 1, 2, 4, 8, 12, 14 and 16 weeks. Samples were cultured for aerobic colony counts, Staphylococcus aureus and E. coli.

Results

The total aerobic colony counts were 47% lower on the treated ward compared with the non-treated ward over the study period (p = 0.02). The colony counts for Staphylococcus aureus and E. coli were low on both wards. During the first registration period, the incidence of HAI was 22.7% and 20.0% on the non-treated and subsequently treated ward respectively. On the second occasion, after treatment, the incidence was 25.0% and 12.5% (treated ward) respectively (p = 0.0001).

Conclusions

The use of a long-lasting antimicrobial organosilane coating appears to reduce the bioburden and reduce HAI. Since the incidence of HAI varies substantially over time, longer observation times are needed.
Microtubule cytoskeleton-disrupting activity of MWCNTs: applications in cancer treatment
Authors: Hevia Lorena García , Fanarraga Mónica L.
Published: December 2020

Microtubules and carbon nanotubes (CNTs), and more particularly multi-walled CNTs (MWCNTs), share many mechanical and morphological similarities that prompt their association into biosynthetic tubulin filaments both, in vitro and in vivo. Unlike CNTs, microtubules are highly dynamic protein polymers that, upon interaction with these nanomaterials, display enhanced stability that has critical consequences at the cellular level. Among others, CNTs prompt ectopic (acentrosomal) microtubule nucleation and the disassembly of the centrosome, causing a dramatic cytoskeletal reorganization. These changes in the microtubule pattern trigger the generation of ineffective biomechanical forces that result in migration defects, and ultimately in spindle-assembly checkpoint (SAC) blockage and apoptosis. In this review, we describe the molecular mechanism involved in the intrinsic interference of CNTs with the microtubule dynamics and illustrate the consequences of this effect on cell biomechanics. We also discuss the potential application of these synthetic microtubule-stabilizing agents as synergetic agents to boost the effect of classical chemotherapy that includes spindle poisons (i.e. paclitaxel) or DNA interfering agents (5-fluorouracil)-, and list some of the advantages of the use of MWCNTs as adjuvant agents in preventing cell resistance to chemotherapy.
The effectiveness of pediatric obesity prevention policies: a comprehensive systematic review and dose–response meta-analysis of controlled clinical trials
Authors: Taghizadeh Shahnaz , Farhangi Mahdieh Abbasalizad
Published: December 2020

Background

Childhood obesity persists as a serious public health problem. In the current meta-analysis, we summarized the results of controlled trials that evaluated the effect of obesity prevention policies in children and adolescents.

Methods

Three databases (SCOPUS, PubMed and Embase) were searched for studies published before the 6th April 2020, by reported outcome measures of body mass index (BMI) and BMI-Zscore. Forty-seven studies reported BMI, while 45 studies reported BMI-Zscoreas final outcome.

Results

The results showed that the obesity-prevention policies had significant effect in reducing BMI (WMD: − 0.127; CI − 0.198, − 0.056; P < 0.001). These changes were not significant for BMI-Zscore(WMD: − 0.020; CI − 0.061, 0.021; P = 0.340). In dose–response meta-analysis, a non-linear association was reported between the duration of intervention and BMI (Pnonlinearity < 0.001) as well as BMI-Zscore(Pnonlinearity = 0.023). In subgroup analysis, the more favorite results were observed for 5–10 years old, with combination of physical activity and diet as intervention materials.

Conclusion

In conclusion, the obesity prevention policies in short-term periods of less than 2 years, in rather early age of school with approaches of change in both of diet and physical activity, could be more effective in prevention of childhood obesity.

Trial registrationPROSPERO registration number: CRD42019138359
Co-expression of cancer driver genes: IDH-wildtype glioblastoma-derived tumorspheres
Authors: Yoon Seon-Jin , Son Hye Young , Shim Jin-Kyoung , Moon Ju Hyung , Kim Eui-Hyun , Chang Jong Hee , Teo Wan Yee , Kim Se Hoon , Park Sahng Wook , Huh Yong-Min , Kang Seok-Gu
Published: December 2020

Background

Driver genes of GBM may be crucial for the onset of isocitrate dehydrogenase (IDH)-wildtype (WT) glioblastoma (GBM). However, it is still unknown whether the genes are expressed in the identical cluster of cells. Here, we have examined the gene expression patterns of GBM tissues and patient-derived tumorspheres (TSs) and aimed to find a progression-related gene.

Methods

We retrospectively collected primary IDH-WT GBM tissue samples (n = 58) and tumor-free cortical tissue samples (control, n = 20). TSs are isolated from the IDH-WT GBM tissue with B27 neurobasal medium. Associations among the driver genes were explored in the bulk tissue, bulk cell, and a single cell RNAsequencing techniques (scRNAseq) considering the alteration status of TP53, PTEN, EGFR, and TERT promoter as well as MGMT promoter methylation. Transcriptomic perturbation by temozolomide (TMZ) was examined in the two TSs.

Results

We comprehensively compared the gene expression of the known driver genes as well as MGMT, PTPRZ1, or IDH1. Bulk RNAseq databases of the primary GBM tissue revealed a significant association between TERT and TP53 (p < 0.001, R = 0.28) and its association increased in the recurrent tumor (p  < 0.001, R = 0.86). TSs reflected the tissue-level patterns of association between the two genes (p < 0.01, R = 0.59, n = 20). A scRNAseq data of a TS revealed the TERT and TP53 expressing cells are in a same single cell cluster. The driver-enriched cluster dominantly expressed the glioma-associated long noncoding RNAs. Most of the driver-associated genes were downregulated after TMZ except IGFBP5.

Conclusions

GBM tissue level expression patterns of EGFR, TERT, PTEN, IDH1, PTPRZ1, and MGMT are observed in the GBM TSs. The driver gene-associated cluster of the GBM single cells were enriched with the glioma-associated long noncoding RNAs.
Potential causal factors of CFS/ME: a concise and systematic scoping review of factors researched
Authors: Muller Ashley Elizabeth , Tveito Kari , Bakken Inger Johanne , Flottorp Signe A. , Mjaaland Siri , Larun Lillebeth
Published: December 2020

Background

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is understood as a complex condition, likely triggered and sustained by an interplay of biological, psychological, and social factors. Little oversight exists of the field of causal research. This systematic scoping review explores potential causal factors of CFS/ME as researched by primary studies.

Methods

We searched eight databases for primary studies that examined potential causal factors of CFS/ME. Based on title/abstract review, two researchers independently sorted each study’s factors into nine main categories and 71 subordinate categories, using a system developed with input given during a 2018 ME conference, specialists and representatives from a ME patient advocacy group, and using BMJ Best Practice’s description of CFS/ME etiology. We also extracted data related to study design, size, diagnostic criteria and comparison groups.

Results

We included 1161 primary studies published between January 1979 and June 2019. Based on title/abstract analysis, no single causal factor dominated in these studies, and studies reported a mean of 2.73 factors. The four most common factors were: immunological (297 studies), psychological (243), infections (198), and neuroendocrinal (198). The most frequent study designs were case–control studies (894 studies) comparing CFS/ME patients with healthy participants. More than half of the studies (that reported study size in the title/abstract) included 100 or fewer participants.

Conclusion

The field of causal hypotheses of CFS/ME is diverse, and we found that the studies examined all the main categories of possible factors that we had defined a priori. Most studies were not designed to adequately explore causality, rather to establish hypotheses. We need larger studies with stronger study designs to gain better knowledge of causal factors of CFS/ME.
Minocycline reduces inflammatory response and cell death in a S100B retina degeneration model
Authors: Grotegut Pia , Perumal Natarajan , Kuehn Sandra , Smit Andreas , Dick H. Burkhard , Grus Franz H. , Joachim Stephanie C.
Published: December 2020

Background

Previous studies noted that intravitreal injection of S100B triggered a glaucoma-like degeneration of retina and optic nerve as well as microglia activation after 14 days. The precise role of microglia in our intravitreal S100B model is still unclear. Hence, microglia were inhibited through minocycline. The aim is to investigate whether microglia have a significant influence on the degeneration process or whether they are only a side effect in the model studied here.

Methods

Minocycline was applied daily in rats by intraperitoneal injection using two different concentrations (13.5 mg/kg body weight, 25 mg/kg body weight). One day after treatment start, S100B or PBS was intravitreally injected in one eye per rat. The naïve groups received no injections. This resulted in a total of five groups (naïve n = 14, PBS n = 14, S100B n = 13, 13.5 mg/kg mino n = 15, 25 mg/kg mino n = 15). At day 14, electroretinogram measurements were performed, followed by immunofluorescence and label-free quantitative proteomics analysis. The focus of these investigations was on the survival of RGCs as well as their axons, the response of the microglia, and the identification of further pathological modes of action of S100B.

Results

The best signal transmission was detected via ERG in the 13.5 mg/kg mino group. The inhibition of the microglia protected optic nerve neurofilaments and decreased the negative impact of S100B on RGCs. However, the minocycline treatment could not trigger complete protection of RGCs. Furthermore, in retina and optic nerve, the minocycline treatment reduced the number and activity of S100B-triggered microglia in a concentration-dependent manner. Proteomics analysis showed that S100B application led to numerous metabolic functions and cellular stress, mainly an increased inflammatory response, glycolysis, and mitochondrial dysfunction, which caused oxidative stress in the retina. Importantly, the protective capability of lower dose of minocycline was unraveled by suppressing the apoptotic, inflammatory, and the altered metabolic processes caused by S100B insult in the retina.

Conclusion

Intravitreally injected S100B not only led to a pro-inflammatory microglial reaction, but also a mitochondrial and metabolic dysfunction. Also, these results suggest that an excessive microglial response may be a significant degenerative factor, but not the only trigger for increased cell death.
Cost comparison of two approaches to chiropractic care for patients with acute and sub-acute low Back pain care episodes: a cohort study
Authors: Whedon James M. , Bezdjian Serena , Dennis Patricia , Fischer Vivi-Ann , Russell Robb
Published: December 2020

Background

Low back pain (LBP) imposes a costly burden upon patients, healthcare insurers, and society overall. Spinal manipulation as practiced by chiropractors has been found be cost-effective for treatment of LBP, but there is wide variation among chiropractors in their approach to clinical care, and the most cost-effective approach to chiropractic care is uncertain. To date, little has been published regarding the cost effectiveness of different approaches to chiropractic care. Thus, the current study presents a cost comparison between chiropractic approaches for patients with acute or subacute care episodes for low back pain.

Methods

We employed a retrospective cohort design to examine costs of chiropractic care among patients diagnosed with acute or subacute low back pain. The study time period ranged between 07/01/2016 and 12/22/2017. We compared cost outcomes for patients of two cohorts of chiropractors within health care system: Cohort 1) a general network of providers, and Cohort 2) a network providing conservative evidence-based care for rapid resolution of pain. We used generalized linear regression modeling to estimate the comparative influence of demographic and clinical factors on expenditures.

Results

A total of 25,621 unique patients were included in the analyses. The average cost per patient for Cohort 2 (mean allowed amount $252) was lower compared to Cohort 1 (mean allowed amount $326; 0.77, 95% CI 0.75–0.79,p < .001). Patient and clinician related factors such as health plan, provider region, and sex also significantly influenced costs.

Conclusions

This study comprehensively analyzed cost data associated with the chiropractic care of adults with acute or sub-acute low back pain cared by two cohorts of chiropractic physicians. In general, providers in Cohort 2 were found to be significantly associated with lower costs for patient care as compared to Cohort 1. Utilization of a clinical model characterized by a patient-centered clinic approach and standardized, best-practice clinical protocols may offer lower cost when compared to non-standardized clinical approaches to chiropractic care.
Quality assessment of a clinical next-generation sequencing melanoma panel within the Italian Melanoma Intergroup (IMI)
Authors:   Italian Association for Cancer Research (AIRC) Study Group, Vanni Irene ,   for the Italian Melanoma Intergroup (IMI), Casula Milena , Pastorino Lorenza , Manca Antonella , Dalmasso Bruna , Andreotti Virginia , Pisano Marina , Colombino Maria , Pfeffer Ulrich , Tanda Enrica Teresa , Rozzo Carla , Paliogiannis Panagiotis , Cossu Antonio , Ghiorzo Paola , Palmieri Giuseppe
Published: December 2020

Background

Identification of somatic mutations in key oncogenes in melanoma is important to lead the effective and efficient use of personalized anticancer treatment. Conventional methods focus on few genes per run and, therefore, are unable to screen for multiple genes simultaneously. The use of Next-Generation Sequencing (NGS) technologies enables sequencing of multiple cancer-driving genes in a single assay, with reduced costs and DNA quantity needed and increased mutation detection sensitivity.

Methods

We designed a customized IMI somatic gene panel for targeted sequencing of actionable melanoma mutations; this panel was tested on three different NGS platforms using 11 metastatic melanoma tissue samples in blinded manner between two EMQN quality certificated laboratory.

Results

The detection limit of our assay was set-up to a Variant Allele Frequency (VAF) of 10% with a coverage of at least 200x. All somatic variants detected by all NGS platforms with a VAF ≥ 10%, were also validated by an independent method. The IMI panel achieved a very good concordance among the three NGS platforms.

Conclusion

This study demonstrated that, using the main sequencing platforms currently available in the diagnostic setting, the IMI panel can be adopted among different centers providing comparable results.
Impact of clinical and sociodemographic factors on fatigue among patients with substance use disorder: a cohort study from Norway for the period 2016–2020
Authors:   for the INTRO-HCV Study Group, Vold Jørn Henrik , Gjestad Rolf , Aas Christer F. , Chalabianloo Fatemeh , Skurtveit Svetlana , Løberg Else-Marie , Johansson Kjell Arne , Fadnes Lars Thore
Published: December 2020

Background

The impact of clinical and sociodemographic factors on fatigue remains unknown among patients with substance use disorders (SUD). This study aims to evaluate fatigue among patients with SUD using a nine-item fatigue severity scale (FSS-9) and identify the impact that clinical and sociodemographic factors – such as injecting substance use, chronic infectious diseases, liver fibrosis, opioid agonist therapy (OAT), debt difficulties, and housing situation – have on fatigue.

Methods

We used data from a cohort of patients with SUD in Norway with annual health assessments surveying FSS-9 and some clinical and sociodemographic factors. A total of 915 FSS-9 measurements were collected from 654 patients during the period 2016–2020. We defined baseline as the first annual health assessment when the health assessments were listed chronologically. Time was defined as years from baseline. We used a linear mixed model to analyse whether the clinical and sociodemographic factors affected the FSS-9 sum score, presented with beta coefficients (β) with 95% confidence intervals (CI).

Results

The mean sum score of the FSS-9 was 43 (standard deviation: 16) at baseline. Females compared with males (adjusted mean difference of FSS-9 sum score: 4.1, 95% CI: 1.3–7.0), having debt difficulties compared with having no debt difficulties (2.9;0.4–5.3), and frequent use of benzodiazepines (5.7;3.0–8.4) or amphetamines (-5.0;-8.0– -2.0) compared to less frequent or no use of these substances changed the FSS-9 baseline sum score. The other clinical and sociodemographic factors did not predict any clinically relevant change in the FSS-9 sum score from baseline to the following health assessments.

Conclusion

Patients with SUD suffer from high levels of fatigue. Female patients, patients with debt difficulties, and those with extensive use of benzodiazepines are at particular risk of being fatigued. This should be taken into consideration when planning health services.
Cost-effectiveness of the Adaptive Implementation of Effective Programs Trial (ADEPT): approaches to adopting implementation strategies
Authors: Eisman Andria B. , Hutton David W. , Prosser Lisa A. , Smith Shawna N. , Kilbourne Amy M.
Published: December 2020

Background

Theory-based methods to support the uptake of evidence-based practices (EBPs) are critical to improving mental health outcomes. Implementation strategy costs can be substantial, and few have been rigorously evaluated. The purpose of this study is to conduct a cost-effectiveness analysis to identify the most cost-effective approach to deploying implementation strategies to enhance the uptake of Life Goals, a mental health EBP.

Methods

We used data from a previously conducted randomized trial to compare the cost-effectiveness of Replicating Effective Programs (REP) combined with external and/or internal facilitation among sites non-responsive to REP. REP is a low-level strategy that includes EBP packaging, training, and technical assistance. External facilitation (EF) involves external expert support, and internal facilitation (IF) augments EF with protected time for internal staff to support EBP implementation. We developed a decision tree to assess 1-year costs and outcomes for four implementation strategies: (1) REP only, (2) REP+EF, (3) REP+EF add IF if needed, (4) REP+EF/IF. The analysis used a 1-year time horizon and assumed a health payer perspective. Our outcome was quality-adjusted life years (QALYs). The economic outcome was the incremental cost-effectiveness ratio (ICER). We conducted deterministic and probabilistic sensitivity analysis (PSA).

Results

Our results indicate that REP+EF add IF is the most cost-effective option with an ICER of $593/QALY. The REP+EF/IF and REP+EF only conditions are dominated (i.e., more expensive and less effective than comparators). One-way sensitivity analyses indicate that results are sensitive to utilities for REP+EF and REP+EF add IF. The PSA results indicate that REP+EF, add IF is the optimal strategy in 30% of iterations at the threshold of $100,000/QALY.

Conclusions

Our results suggest that the most cost-effective implementation support begins with a less intensive, less costly strategy initially and increases as needed to enhance EBP uptake. Using this approach, implementation support resources can be judiciously allocated to those clinics that would most benefit. Our results were not robust to changes in the utility measure. Research is needed that incorporates robust and relevant utilities in implementation studies to determine the most cost-effective strategies. This study advances economic evaluation of implementation by assessing costs and utilities across multiple implementation strategy combinations.

Trial registration

ClinicalTrials.gov Identifier:NCT02151331, 05/30/2014.
Incidence and locations of deep venous thrombosis of the lower extremity following surgeries of tibial plateau fractures: a prospective cohort study
Authors: Li Junyong , Zhu Yanbin , Chen Wei , Zhao Kuo , Zhang Junzhe , Meng Hongyu , Jin Zhucheng , Ye Dandan , Zhang Yingze
Published: December 2020

Objective

To investigate the incidence of deep venous thrombosis (DVT) of the lower extremities following surgeries of tibial plateau fractures.

Methods

Retrospective analysis of the prospectively collected data on patients undergoing surgeries of tibial plateau fractures between October 2014 and December 2018 was conducted. Duplex ultrasonography (DUS) was used to screen for postoperative DVT of the bilateral lower extremities. Data on demographics, comorbidities, injury, surgery, and laboratory biomarkers at admission were collected. Univariate analyses and multivariate logistic regression analyses were used to identify the independent risk factors associated with DVT.

Results

Among 987 patients included, 46 (4.7%) had postoperative DVT, with incidence rate of 1.0% for proximal and 3.7% for distal DVT. The average interval between operation and DVT was 8.3 days (median, 5.8 days), ranging from 2 to 42 days. DVT involved the injured extremity in 39 (84.8%) patients, both the injured and uninjured extremity in 2 patients (4.3%) and only the uninjured extremity in 5 patients (10.9%). Five risk factors were identified to be associated with postoperative DVT, including age (≥ 41 vs < 41 years) (OR 3.08; 95% CI 1.43–6.61; p = 0.004), anesthesia (general vs regional) (OR 2.08; 95% CI 1.12–3.85; p = 0.021), hyponatremia (OR 2.21; 95% CI 1.21–4.06; p = 0.010), prolonged surgical time (OR 1.04; 95% CI 1.01–1.07; p = 0.017) and elevated D-dimer level (OR 2.79; 95% CI 1.34–4.83; p = 0.004).

Conclusion

These epidemiologic data may be helpful in individualized assessment, risk stratification, and development of targeted prevention programs.
Surgical procedure of segmentectomy as a possible cause of postoperative cerebral embolism: a case report
Authors: Chen Peirui , Qing Qiusha , Diao Mingqiang , Sun Xiaokang , Yang Junrong , Lv Jing
Published: December 2020

Background

Cerebral embolism after lobectomy is a life-threatening complication during the early postoperative period. However, it is unclear if cerebral embolism can develop after segmentectomy.

Case presentation

We experienced a case of a 37-year-old man who demonstrated early symptom of acute ischemic stroke in early postoperative period after right upper posterior segmentectomy and performed intra-arterial mechanical thrombectomy (IAMT) successfully.

Conclusions

Long and irregular pulmonary vein stump (PVS) and endothelial injury caused by surgical procedure may lead to cerebral embolism after segmentectomy. We believe that doing preoperative pulmonary vascular assessment and using appropriate surgical procedure may reduce the rate of cerebral embolism.
From natural dye to herbal medicine: a systematic review of chemical constituents, pharmacological effects and clinical applications of indigo naturalis
Authors: Qi-yue Yang , Ting Zhang , Ya-nan He , Sheng-jie Huang , Xuan Deng , Li Han , Chun-guang Xie
Published: December 2020

Background

Indigo naturalis is a blue dye in ancient, as well as an extensive used traditional Chinese medicine. It has a wide spectrum of pharmacological properties and can be used to treat numerous ailments such as leukemia, psoriasis, and ulcerative colitis. This article aims to expand our understanding of indigo naturalis in terms of its chemical constituents, pharmacological action and clinical applications.

Methods

We searched PubMed, web of science, CNKI, Google academic, Elsevier and other databases with the key words of “Indigo naturalis”, and reviewed and sorted out the modern research of indigo naturalis based on our research results.

Results

We outlined the traditional manufacturing process, chemical composition and quality control of indigo naturalis, systematically reviewed traditional applictions, pharmacological activities and mechanism of indigo naturalis, and summarized its clinical trials about treatment of psoriasis, leukemia and ulcerative colitis.

Conclusions

Indigo naturalis has a variety of pharmacological activities, such as anti-inflammatory, antioxidant, antibacterial, antiviral, immunomodulatory and so on. It has very good clinical effect on psoriasis, leukemia and ulcerative colitis. However, it should be noted that long-term use of indigo naturalis may produce some reversible adverse reactions. In summarize, indigo naturalis is an extremely important drug with great value and potential.
Colonization by native species enhances the carbon storage capacity of exotic mangrove monocultures
Authors: He Ziying , Sun Huaye , Peng Yisheng , Hu Zhan , Cao Yingjie , Lee Shing Yip
Published: December 2020

Background

The fast-growing introduced mangrove Sonneratia apetala is widely used for mangrove afforestation and reforestation in China. Some studies suggested that this exotic species outperforms native species in terms of carbon sequestration potential. This study tested the hypothesis that multi-species mangrove plantations might have higher carbon sequestration potential than S. apetala monocultures.

Results

Our field measurements at Hanjiang River Estuary (Guangdong province, China) showed that the carbon stock (46.0 ± 3.0 Mg/ha) in S. apetala plantations where the native Kandelia obovata formed an understory shrub layer was slightly higher than that in S. apetala monocultures (36.6 ± 1.3 Mg/ha). Moreover, the carbon stock in monospecific K. obovata stands (106.6 ± 1.4 Mg/ha) was much larger than that of S. apetala monocultures.

Conclusions

Our results show that K. obovata monocultures may have a higher carbon accumulation rate than S. apetala monocultures. Planting K. obovata seedlings in existing S. apetala plantations may enhance the carbon sink associated with these plantations.
A graphic elicitation technique to represent patient rights
Authors: McGowan Catherine R. , Hellman Nora , Baxter Louisa , Chakma Sonali , Nahar Samchun , Daula Ahasan Ud , Rowe Kelly , Gilday Josie , Kingori Patricia , Pounds Rachel , Cummings Rachael
Published: December 2020

Background

A patient charter is an explicit declaration of the rights of patients within a particular health care setting. In early 2020 the Save the Children Emergency Health Unit deployed to Cox’s Bazar Bangladesh to support the establishment of a severe acute respiratory infection isolation and treatment centre as part of the COVID-19 response. We developed a charter of patient rights and had it translated into Bangla and Burmese; however, the charter remained inaccessible to Rohingya and members of the host community with low literacy.

Methods

To both visualise and contextualise the patient charter we undertook a graphic elicitation method involving both the Rohingya and host communities. We carried out two focus group discussions during which we discussed the charter and agreed how best to illustrate the individual rights contained therein.

Results

Logistical constraints and infection prevention and control procedures limited our ability to follow up with the original focus group participants and to engage in back-translation as we had planned; however, we were able to elicit rich descriptions of each right. Reflecting on our method we were able to identify several key learnings relating to: 1) our technique for eliciting feedback on the charter verbatim versus a broader discussion of concepts referenced within each right, 2) our decision to include both men and women in the same focus group, 3) our decision to ask focus group participants to describe specific features of each illustration and how this benefited the inclusivity of our illustrations, and 4) the potential of the focus groups to act as a means to introduce the charter to communities.

Conclusions

Though executing our method was operationally challenging we were able to create culturally appropriate illustrations to accompany our patient charter. In contexts of limited literacy it is possible to enable access to critical clinical governance and accountability tools.
Country and gender differences in the association between violence and cigarette smoking among youth
Authors: Abu-Rmeileh Niveen M. E. , Alderete Ethel , Husseini Abdullatif , Livaudais-Toman Jennifer , Pérez-Stable Eliseo J.
Published: December 2020

Background

Exposure to violence in youth may be associated with substance use and other adverse health effects. This study examined cigarette smoking in two middle-income areas with different levels and types of exposure to violence.

Methods

Association of exposure to verbal and physical violence with cigarette smoking in the West Bank oPt (2008) and in Jujuy Argentina (2006) was examined using cross-sectional surveys of 14 to 17-year old youth in 7th to 10th grade using probabilistic sampling.

Results

Violence exposure rates were more than double for Palestinian girls (99.6% vs. 41.2%) and boys (98.7% vs. 41.1%) compared with Argentinians. The rate of current cigarette smoking was significantly higher among Argentinian girls compared with Palestinian girls (33.1% vs. 7.1%, p < 0.001). Exposure to verbal violence from family and to physical violence increased the odds of current cigarette smoking, respectively, among Argentinian girls (aOR = 1.3, 95% CI = 1.0–1.7; aOR = 2.5, 95%CI = 1.7–3.8), Palestinian girls (aOR 2.2, 95%CI = 1.1–2.4; aOR = 2.0, 95%CI = 1.1–3.6) and Argentinian boys (aOR = 1.5, 95%CI = 1.1–2.0; aOR = 2.2, 95%CI = 1.6–3.0), but not among Palestinian boys.

Conclusion

Findings highlight the importance of producing context and gender specific evidence from exposure to violence, to inform and increase the impact of targeted smoking prevention strategies.
New agents and regimens for diffuse large B cell lymphoma
Authors: Wang Liang , Li Lin-rong , Young Ken H.
Published: December 2020

As a widely recognized standard regimen, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is able to cure two-thirds patients with diffuse large B cell lymphoma (DLBCL), and the remaining patients suffer from refractory or relapsed disease due to resistance to R-CHOP and fare poorly. Unsatisfied outcomes for those relapsed/refractory patients prompted efforts to discover new treatment approaches for DLBCL, including chimeric antigen receptor T cells, bispecific T cell engagers, immunomodulatory drugs, immune checkpoint inhibitors, monoclonal antibodies, antibody–drug conjugates, molecular pathway inhibitors, and epigenetic-modifying drugs. Herein, up-to-date data about the most promising treatment approaches for DLBCL are recapitulated, and novel genetic classification systems are introduced to guide individualized treatment for DLBCL.
BRAFV600E mutation impinges on gut microbial markers defining novel biomarkers for serrated colorectal cancer effective therapies
Authors: Trivieri Nadia , Pracella Riccardo , Cariglia Maria Grazia , Panebianco Concetta , Parrella Paola , Visioli Alberto , Giani Fabrizio , Soriano Amata Amy , Barile Chiara , Canistro Giuseppe , Latiano Tiziana Pia , Dimitri Lucia , Bazzocchi Francesca , Cassano Dario , Vescovi Angelo L. , Pazienza Valerio , Binda Elena
Published: December 2020

Background

Colorectal cancer (CRC) harboring BRAFV600E mutation exhibits low response to conventional therapy and poorest prognosis. Due to the emerging correlation between gut microbiota and CRC carcinogenesis, we investigated in serrated BRAFV600E cases the existence of a peculiar fecal microbial fingerprint and specific bacterial markers, which might represent a tool for the development of more effective clinical strategies.

Methods

By injecting human CRC stem-like cells isolated from BRAFV600E patients in immunocompromised mice, we described a new xenogeneic model of this subtype of CRC. By performing bacterial 16S rRNA sequencing, the fecal microbiota profile was then investigated either in CRC-carrying mice or in a cohort of human CRC subjects. The microbial communities’ functional profile was also predicted. Data were compared with Mann-Whitney U, Welch’s t-test for unequal variances and Kruskal-Wallis test with Benjamini–Hochberg false discovery rate (FDR) correction, extracted as potential BRAF class biomarkers and selected as model features. The obtained mean test prediction scores were subjected to Receiver Operating characteristic (ROC) analysis. To discriminate the BRAF status, a Random Forest classifier (RF) was employed.

Results

A specific microbial signature distinctive for BRAF status emerged, being the BRAF-mutated cases closer to healthy controls than BRAF wild-type counterpart. In agreement, a considerable score of correlation was also pointed out between bacteria abundance from BRAF-mutated cases and the level of markers distinctive of BRAFV600E pathway, including those involved in inflammation, innate immune response and epithelial-mesenchymal transition. We provide evidence that two candidate bacterial markers, Prevotella enoeca and Ruthenibacterium lactatiformans, more abundant in BRAFV600E and BRAF wild-type subjects respectively, emerged as single factors with the best performance in distinguishing BRAF status (AUROC = 0.72 and 0.74, respectively, 95% confidence interval). Furthermore, the combination of the 10 differentially represented microorganisms between the two groups improved performance in discriminating serrated CRC driven by BRAF mutation from BRAF wild-type CRC cases (AUROC = 0.85, 95% confidence interval, 0.69–1.01).

Conclusion

Overall, our results suggest that BRAFV600E mutation itself drives a distinctive gut microbiota signature and provide predictive CRC-associated bacterial biomarkers able to discriminate BRAF status in CRC patients and, thus, useful to devise non-invasive patient-selective diagnostic strategies and patient-tailored optimized therapies.
Multiple trauma management in mountain environments - a scoping review
Authors: Sumann G. , Moens D. , Brink B. , Brodmann Maeder M. , Greene M. , Jacob M. , Koirala P. , Zafren K. , Ayala M. , Musi M. , Oshiro K. , Sheets A. , Strapazzon G. , Macias D. , Paal P.
Published: December 2020

Background

Multiple trauma in mountain environments may be associated with increased morbidity and mortality compared to urban environments.

Objective

To provide evidence based guidance to assist rescuers in multiple trauma management in mountain environments.

Eligibility criteria

All articles published on or before September 30th 2019, in all languages, were included. Articles were searched with predefined search terms.

Sources of evidence

PubMed, Cochrane Database of Systematic Reviews and hand searching of relevant studies from the reference list of included articles.

Charting methods

Evidence was searched according to clinically relevant topics and PICO questions.

Results

Two-hundred forty-seven articles met the inclusion criteria. Recommendations were developed and graded according to the evidence-grading system of the American College of Chest Physicians. The manuscript was initially written and discussed by the coauthors. Then it was presented to ICAR MedCom in draft and again in final form for discussion and internal peer review. Finally, in a face-to-face discussion within ICAR MedCom consensus was reached on October 11th 2019, at the ICAR fall meeting in Zakopane, Poland.

Conclusions

Multiple trauma management in mountain environments can be demanding. Safety of the rescuers and the victim has priority. A crABCDE approach, with haemorrhage control first, is central, followed by basic first aid, splinting, immobilisation, analgesia, and insulation. Time for on-site medical treatment must be balanced against the need for rapid transfer to a trauma centre and should be as short as possible. Reduced on-scene times may be achieved with helicopter rescue. Advanced diagnostics (e.g. ultrasound) may be used and treatment continued during transport.