bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical implications for dopaminergic and functional neuroimage research in cognitive symptoms of Parkinson’s disease
Authors: Hirano Shigeki
Published: April 2021

Evidence from dopaminergic image and cerebral blood flow/metabolism images have shed light on symptomatology of cognitive aspects in brain physiology of healthy human as well as patients with Parkinson’s disease. Cognitive impairment in Parkinson’s disease is characterized by executive, visuospatial, attentional disturbances. Dopaminergic system includes triadic parallel pathways. The mesostriatal pathway consist of posterolateral putamen and motor areas, the mesocortical pathway of dorsal caudate nucleus and dorsolateral prefrontal cortex, and the mesolimbic pathway of ventral striatum, anterior cingulate cortex. The mesocortical pathway is responsible for the executive function which may change by administration of dopaminergic medication. The mesolimbic pathway is associated with motivation and reward prediction which may result in depression or apathy when dopamine level was suboptimal, impulse control disorder and punding when dopamine was over the optimal level. Abnormal brain metabolism/perfusion related to cognitive impairment in Parkinson’s disease are relatively reduced activity located in frontal and parietal association areas and relatively increased activity in the cerebellum. In the anterior brain, the mesocortical pathway, is responsible for verbal memory and executive function, which originates with caudate dopaminergic system and account for mild cognitive impairment of Parkinson’s disease. The posterior brain system which includes the parietal, temporal, and occipital cortices, is responsible for the memory and visuospatial function, and related to cholinergic dysfunction and possibly glucocerebrosidase gene variants, relating to dementia in Parkinson’s disease. The role of cerebellum in Parkinson’s disease remains unclear but emerging evidence suggests that it may relate to the sequencing detection and affective symptoms. The dual syndrome hypothesis is helpful for understanding the mechanism of cognitive impairment in Parkinson’s disease and optimal symptom management.
The burden attributable to headache disorders in children and adolescents in Lithuania: estimates from a national schools-based study
Authors: Genc Diana , Vaičienė-Magistris Nerija , Zaborskis Apolinaras , Şaşmaz Tayyar , Tunç Aylin Yeniocak , Uluduz Derya , Wöber Christian , Wöber-Bingöl Çiçek , Steiner Timothy J.
Published: April 2021

Background

We recently showed headache to be common in children (aged 7–11 years) and adolescents (aged 12–17) in Lithuania. Here we provide evidence from the same study of the headache-attributable burden.

Methods

Following the generic protocol for Lifting The Burden’s global schools-based study, this cross-sectional survey administered self-completed structured questionnaires to pupils within classes in 24 nationally representative schools selected from seven regions of the country. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH; defined as mild headache with usual duration < 1 h). Burden enquiry was conducted in multiple domains.

Results

Questionnaires were completed by 2505 pupils (1382 children, 1123 adolescents; participating proportion 67.4%), of whom 1858 reported headache in the preceding year, with mean frequency (±SD) of 3.7 ± 4.5 days/4 weeks and mean duration of 1.6 ± 1.9 h. Mean proportion of time in ictal state, estimated from these, was 0.9% (migraine 1.5%, probable medication-overuse headache [pMOH] 10.9%). Mean intensity on a scale of 1–3 was 1.6 ± 0.6 (mild-to-moderate). Symptomatic medication was consumed on 1.5 ± 2.8 days/4 weeks. Lost school time was 0.5 ± 1.5 days/4 weeks (migraine 0.7 ± 1.5, pMOH 5.0 ± 7.8) based on recall, but about 50% higher for migraine according to actual absences recorded in association with reported headache on the preceding day. More days were reported with limited activity (overall 1.2 ± 2.4, migraine 1.5 ± 2.2, pMOH 8.4 ± 8.5) than lost from school. One in 30 parents (3.3%) missed work at least once in 4 weeks because of their son’s or daughter’s headache. Emotional impact and quality-of-life scores generally reflected other measures of burden, with pMOH causing greatest detriments, followed by migraine and tension-type headache, and UdH least. Burdens were greater in adolescents than children as UdH differentiated into adult headache types.

Conclusions

Headache in children and adolescents in Lithuania is mostly associated with modest symptom burden. However, the consequential burdens, in particular lost school days, are far from negligible for migraine (which is prevalent) and very heavy for pMOH (which, while uncommon in children, becomes four-fold more prevalent in adolescents). These findings are of importance to both health and educational policies in Lithuania.
ChIP-BIT2: a software tool to detect weak binding events using a Bayesian integration approach
Authors: Chen Xi , Shi Xu , Neuwald Andrew F. , Hilakivi-Clarke Leena , Clarke Robert , Xuan Jianhua
Published: April 2021

Background

ChIP-seq combines chromatin immunoprecipitation assays with sequencing and identifies genome-wide binding sites for DNA binding proteins. While many binding sites have strong ChIP-seq ‘peak’ observations and are well captured, there are still regions bound by proteins weakly, with a relatively low ChIP-seq signal enrichment. These weak binding sites, especially those at promoters and enhancers, are functionally important because they also regulate nearby gene expression. Yet, it remains a challenge to accurately identify weak binding sites in ChIP-seq data due to the ambiguity in differentiating these weak binding sites from the amplified background DNAs.

Results

ChIP-BIT2 (http://sourceforge.net/projects/chipbitc/) is a software package for ChIP-seq peak detection. ChIP-BIT2 employs a mixture model integrating protein and control ChIP-seq data and predicts strong or weak protein binding sites at promoters, enhancers, or other genomic locations. For binding sites at gene promoters, ChIP-BIT2 simultaneously predicts their target genes. ChIP-BIT2 has been validated on benchmark regions and tested using large-scale ENCODE ChIP-seq data, demonstrating its high accuracy and wide applicability.

Conclusion

ChIP-BIT2 is an efficient ChIP-seq peak caller. It provides a better lens to examine weak binding sites and can refine or extend the existing binding site collection, providing additional regulatory regions for decoding the mechanism of gene expression regulation.
Predicting tumor response to drugs based on gene-expression biomarkers of sensitivity learned from cancer cell lines
Authors: Li Yuanyuan , Umbach David M. , Krahn Juno M. , Shats Igor , Li Xiaoling , Li Leping
Published: April 2021

Background

Human cancer cell line profiling and drug sensitivity studies provide valuable information about the therapeutic potential of drugs and their possible mechanisms of action. The goal of those studies is to translate the findings from in vitro studies of cancer cell lines into in vivo therapeutic relevance and, eventually, patients’ care. Tremendous progress has been made.

Results

In this work, we built predictive models for 453 drugs using data on gene expression and drug sensitivity (IC50) from cancer cell lines. We identified many known drug-gene interactions and uncovered several potentially novel drug-gene associations. Importantly, we further applied these predictive models to ~ 17,000 bulk RNA-seq samples from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database to predict drug sensitivity for both normal and tumor tissues. We created a web site for users to visualize and download our predicted data (https://manticore.niehs.nih.gov/cancerRxTissue). Using trametinib as an example, we showed that our approach can faithfully recapitulate the known tumor specificity of the drug.

Conclusions

We demonstrated that our approach can predict drugs that 1) are tumor-type specific; 2) elicit higher sensitivity from tumor compared to corresponding normal tissue; 3) elicit differential sensitivity across breast cancer subtypes. If validated, our prediction could have relevance for preclinical drug testing and in phase I clinical design.
The Pectobacterium pangenome, with a focus on Pectobacterium brasiliense, shows a robust core and extensive exchange of genes from a shared gene pool
Authors: Jonkheer Eef M. , Brankovics Balázs , Houwers Ilse M. , van der Wolf Jan M. , Bonants Peter J. M. , Vreeburg Robert A. M. , Bollema Robert , de Haan Jorn R. , Berke Lidija , Smit Sandra , de Ridder Dick , van der Lee Theo A. J.
Published: April 2021

Background

Bacterial plant pathogens of the Pectobacterium genus are responsible for a wide spectrum of diseases in plants, including important crops such as potato, tomato, lettuce, and banana. Investigation of the genetic diversity underlying virulence and host specificity can be performed at genome level by using a comprehensive comparative approach called pangenomics. A pangenomic approach, using newly developed functionalities in PanTools, was applied to analyze the complex phylogeny of the Pectobacterium genus. We specifically used the pangenome to investigate genetic differences between virulent and avirulent strains of P. brasiliense, a potato blackleg causing species dominantly present in Western Europe.

Results

Here we generated a multilevel pangenome for Pectobacterium, comprising 197 strains across 19 species, including type strains, with a focus on P. brasiliense. The extensive phylogenetic analysis of the Pectobacterium genus showed robust distinct clades, with most detail provided by 452,388 parsimony-informative single-nucleotide polymorphisms identified in single-copy orthologs. The average Pectobacterium genome consists of 47% core genes, 1% unique genes, and 52% accessory genes. Using the pangenome, we zoomed in on differences between virulent and avirulent P. brasiliense strains and identified 86 genes associated to virulent strains. We found that the organization of genes is highly structured and linked with gene conservation, function, and transcriptional orientation.

Conclusion

The pangenome analysis demonstrates that evolution in Pectobacteria is a highly dynamic process, including gene acquisitions partly in clusters, genome rearrangements, and loss of genes. Pectobacterium species are typically not characterized by a set of species-specific genes, but instead present themselves using new gene combinations from the shared gene pool. A multilevel pangenomic approach, fusing DNA, protein, biological function, taxonomic group, and phenotypes, facilitates studies in a flexible taxonomic context.
Predicting the allergenicity of legume proteins using a PBMC gene expression assay
Authors: Smits Mark , Meijerink Marjolein , Le Thuy-My , Knulst André , de Jong Aard , Caspers Martinus Petrus Maria , Lima Everton Souto , Babé Lilia , Ladics Gregory , McClain Scott , Houben Geert , Verhoeckx Kitty
Published: April 2021

Background

Food proteins differ in their allergenic potential. Currently, there is no predictive and validated bio-assay to evaluate the allergenicity of novel food proteins. The objective of this study was to investigate the potential of a human peripheral blood mononuclear cell (PBMC) gene expression assay to identify biomarkers to predict the allergenicity of legume proteins.

Results

PBMCs from healthy donors were exposed to weakly and strongly allergenic legume proteins (2S albumins, and 7S and 11S globulins from white bean, soybean, peanut, pea and lupine) in three experiments. Possible biomarkers for allergenicity were investigated by exposing PBMCs to a protein pair of weakly (white bean) and strongly allergenic (soybean) 7S globulins in a pilot experiment. Gene expression was measured by RNA-sequencing and differentially expressed genes were selected as biomarkers. 153 genes were identified as having significantly different expression levels to the 7S globulin of white bean compared to soybean. Inclusion of multiple protein pairs from 2S albumins (lupine and peanut) and 7S globulins (white bean and soybean) in a larger study, led to the selection of CCL2, CCL7, and RASD2 as biomarkers to distinguish weakly from strongly allergenic proteins. The relevance of these three biomarkers was confirmed by qPCR when PBMCs were exposed to a larger panel of weakly and strongly allergenic legume proteins (2S albumins, and 7S and 11S globulins from white bean, soybean, peanut, pea and lupine).

Conclusions

The PBMC gene expression assay can potentially distinguish weakly from strongly allergenic legume proteins within a protein family, though it will be challenging to develop a generic method for all protein families from plant and animal sources. Graded responses within a protein family might be of more value in allergenicity prediction instead of a yes or no classification.
Defining the temporal evolution of gut dysbiosis and inflammatory responses leading to hepatocellular carcinoma in Mdr2 −/− mouse model
Authors: Behary J. , Raposo A. E. , Amorim N. M. L. , Zheng H. , Gong L. , McGovern E. , Chen J. , Liu K. , Beretov J. , Theocharous C. , Jackson M. T. , Seet-Lee J. , McCaughan G. W. , El-Omar E. M. , Zekry A.
Published: April 2021

Background

Emerging evidence implicates the gut microbiome in liver inflammation and hepatocellular carcinoma (HCC) development. We aimed to characterize the temporal evolution of gut dysbiosis, in relation to the phenotype of systemic and hepatic inflammatory responses leading to HCC development. In the present study, Mdr2 −/− mice were used as a model of inflammation-based HCC. Gut microbiome composition and function, in addition to serum LPS, serum cytokines/chemokines and intrahepatic inflammatory genes were measured throughout the course of liver injury until HCC development.

Results

Early stages of liver injury, inflammation and cirrhosis, were characterized by dysbiosis. Microbiome functional pathways pertaining to gut barrier dysfunction were enriched during the initial phase of liver inflammation and cirrhosis, whilst those supporting lipopolysaccharide (LPS) biosynthesis increased as cirrhosis and HCC ensued. In parallel, serum LPS progressively increased during the course of liver injury, corresponding to a shift towards a systemic Th1/Th17 proinflammatory phenotype. Alongside, the intrahepatic inflammatory gene profile transitioned from a proinflammatory phenotype in the initial phases of liver injury to an immunosuppressed one in HCC. In established HCC, a switch in microbiome function from carbohydrate to amino acid metabolism occurred.

Conclusion

In Mdr2 −/− mice, dysbiosis precedes HCC development, with temporal evolution of microbiome function to support gut barrier dysfunction, LPS biosynthesis, and redirection of energy source utilization. A corresponding shift in systemic and intrahepatic inflammatory responses occurred supporting HCC development. These findings support the notion that gut based therapeutic interventions could be beneficial early in the course of liver disease to halt HCC development.
Correlation between the spatial distribution and colony size was common for monogenetic bacteria in laboratory conditions
Authors: Xue Heng , Kurokawa Masaomi , Ying Bei-Wen
Published: April 2021

Background

Geographically separated population growth of microbes is a common phenomenon in microbial ecology. Colonies are representative of the morphological characteristics of this structured population growth. Pattern formation by single colonies has been intensively studied, whereas the spatial distribution of colonies is poorly investigated.

Results

The present study describes a first trial to address the questions of whether and how the spatial distribution of colonies determines the final colony size using the model microorganism Escherichia coli, colonies of which can be grown under well-controlled laboratory conditions. A computational tool for image processing was developed to evaluate colony density, colony size and size variation, and the Voronoi diagram was applied for spatial analysis of colonies with identical space resources. A positive correlation between the final colony size and the Voronoi area was commonly identified, independent of genomic and nutritional differences, which disturbed the colony size and size variation.

Conclusions

This novel finding of a universal correlation between the spatial distribution and colony size not only indicated the fair distribution of spatial resources for monogenetic colonies growing with identical space resources but also indicated that the initial localization of the microbial colonies decided by chance determined the fate of the subsequent population growth. This study provides a valuable example for quantitative analysis of the complex microbial ecosystems by means of experimental ecology.
The impact of successful chronic total occlusion percutaneous coronary intervention on long-term clinical outcomes in real world
Authors: Gong Xuhe , Zhou Li , Ding Xiaosong , Chen Hui , Li Hongwei
Published: April 2021

Background

Coronary chronic total occlusions (CTOs) are related to increased risk of adverse clinical outcomes. The optimal treatment strategy for CTO has not been well established. We sought to examine the impact of CTO percutaneous coronary intervention (PCI) on long-term clinical outcome in the real world.

Methods

A total of 592 patients with CTO were enrolled. 29 patients were excluded due to coronary artery bypass grafting (CABG). After exclusion, 563 patients were divided into the no-revascularized group (CTO-NR group, n = 263) and successful revascularized group (CTO-R group, n = 300). The primary endpoint was cardiac death; secondary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, cardiac death, recurrent myocardial infarction, target lesion revascularization, re-hospitalization, heart failure, and stroke.

Results

Percent of Diabetes mellitus (53.2% vs 39.7), Chronic kidney disease (8.7% vs 3.7%), CABG history (7.6% vs 1%), three vessel disease (96.2% vs 90%) and left main coronary artery disease (25.1% vs 13.7%) was significantly higher in the CTO-NR group than in success PCI group (all P < 0.05). Moreover, the CTO-NR group has the lower ejection fraction (EF) (0.58 ± 0.11 vs 0.61 ± 0.1, p = 0.001) and fraction shortening (FS) (0.31 ± 0.07 vs 0.33 ± 0.07, p = 0.002). At a median follow-up of 12 months, CTO revascularization was superior to CTO no-revascularization in terms of cardiac death (adjusted hazard ratio [HR]: 0.27, 95% conference interval [CI] 0.11–0.64). The superiority of CTO revascularization was consistent for MACCE (HR: 0.55, 95% CI 0.35–0.79). At multivariable Cox hazards regression analysis, CTO revascularization remains one of the independent predictors of lower risk of cardiac death and MACCE.

Conclusions

Successful revascularization by PCI may bring more clinical benefits. The presence of low left ventricular ejection fraction (LVEF) and LM-disease was associated with an incidence of cardiac death; CTO revascularization was a protected predictor of cardiac death.

Graphical abstract

Successful revascularization by PCI offered CTO patients more clinical benefits, manifested by lower incidence of cardiac death during follow-up. The presence of LVEF < 0.5 and left main coronary artery disease (LM disease) was associated with an incidence of cardiac death; CTO revascularised was a protected predictor of cardiac death.
Long-term effects (> 24 months) of multiple lifestyle intervention on major cardiovascular risk factors among high-risk subjects: a meta-analysis
Authors: Bergum Hilde , Sandven Irene , Klemsdal Tor Ole
Published: April 2021

Background

The evidence of the long-term effects of multiple lifestyle intervention on cardiovascular risk is uncertain. We aimed to summarize the evidence from randomized clinical trials examining the efficacy of lifestyle intervention on major cardiovascular risk factors in subjects at high cardiovascular risk.

Methods

Eligible trials investigated the impact of lifestyle intervention versus usual care with minimum 24 months follow-up, reporting more than one major cardiovascular risk factor. A literature search updated April 15, 2020 identified 12 eligible studies. The results from individual trials were combined, using fixed and random effect models, using the standardized mean difference (SMD) to estimate effect sizes. Small-study effect was evaluated, and heterogeneity between studies examined, by subgroup and meta-regression analyses, considering patient- and study-level variables.

Results

Small-study effect was not identified. Lifestyle intervention reduced systolic blood pressure modestly with an estimated SMD of − 0.13, 95% confidence interval (CI): − 0.21 to − 0.04, with moderate heterogeneity (I2 = 59%), corresponding to a mean difference of approximately 2 mmHg (MD = − 1.86, 95% CI − 3.14 to − 0.57,p = 0.0046). This effect disappeared in the subgroup of trials judged at low risk of bias (SMD = 0.02, 95% CI − 0.08 to 0.11). For the outcome total cholesterol SMD was − 0.06, 95% CI − 0.13 to 0.00, with no heterogeneity (I2 = 0%), indicating no effect of the intervention.

Conclusion

Lifestyle intervention resulted in only a modest effect on systolic blood pressure and no effect on total cholesterol after 24 months. Further lifestyle trials should consider the challenge of maintaining larger long-term benefits to ensure impact on cardiovascular outcomes.
Smoking, alcohol and opioids effect on coronary microcirculation: an update overview
Authors: Jalali Zahra , Khademalhosseini Morteza , Soltani Narjes , Esmaeili Nadimi Ali
Published: April 2021

Smoking, heavy alcohol drinking and drug abuse are detrimental lifestyle factors leading to loss of million years of healthy life annually. One of the major health complications caused by these substances is the development of cardiovascular diseases (CVD), which accounts for a significant proportion of substance-induced death. Smoking and excessive alcohol consumption are related to the higher risk of acute myocardial infarction. Similarly, opioid addiction, as one of the most commonly used substances worldwide, is associated with cardiac events such as ischemia and myocardial infarction (MI). As supported by many studies, coronary artery disease (CAD) is considered as a major cause for substance-induced cardiac events. Nonetheless, over the last three decades, a growing body of evidence indicates that a significant proportion of substance-induced cardiac ischemia or MI cases, do not manifest any signs of CAD. In the absence of CAD, the coronary microvascular dysfunction is believed to be the main underlying reason for CVD. To date, comprehensive literature reviews have been published on the clinicopathology of CAD caused by smoking and opioids, as well as macrovascular pathological features of the alcoholic cardiomyopathy. However, to the best of our knowledge there is no review article about the impact of these substances on the coronary microvascular network. Therefore, the present review will focus on the current understanding of the pathophysiological alterations in the coronary microcirculation triggered by smoking, alcohol and opioids.
Left-side incarcerated Amyand’s hernia with appendix and caecum provoke by early banana diet: a case report
Authors: Supangat  , Pratama Henggar Allest , Sejati Nanda Eka Sri , Romadhon Brenda Desy , Sulistyani Ina
Published: April 2021

Background

Amyand’s hernia was an unusual condition defined by the presence of an appendix located in the inguinal hernia sac. Its prevalence was 1% of all inguinal hernia in children. The clinical manifestation of Amyand’s hernia was depending on hernia’s stage, an incarcerated hernia will present with an inguinal mass following by pain and motility disorder. It could lead to abdominal distention in the late stage. The common location of Amyand’s hernia was on the right side, the left side was uncommon. Early feeding on infants could provoke symptoms of bowel obstruction (SBO). More than 76% of infants in Java, Indonesia was given banana as solid food in infants before six months old. There is a correlation between the early banana diet and SBO. Amyand’s hernia could present as morbidity of early banana diet.

Case presentation

We describe a case of two months old infant present with an incarcerated left inguinal hernia and history of early banana diet that performed herniotomy procedure. During the operation, we found left-side incarcerated Amyand’s hernia with appendicitis, excoriation caecum, and sticky banana mass.

Conclusion

This case suggest the possibility of early feeding of banana diet may provoke incarceration of an inguinal hernia and if the incarcerated hernia content contains the appendix, then an Amyand's hernia.
Intergenerational support and subjective wellbeing among oldest-old in China: the moderating role of economic status
Authors: Huang Fanghong , Fu Peipei
Published: April 2021

Backgrounds

The oldest-old population is increasing sharply in China, and intergenerational support has been their primary source of caregiving. Although intergenerational support has been found to be associated with wellbeing of older people in previous study, most analysis were from the perspective of children’s characteristics and exchange patterns. This study aims to investigate the impact of different types of intergenerational support on subjective wellbeing among Chinese oldest-old and the variation across groups of different economic status, based on their five-tier of needs (physiological needs, safety needs, love/belonging needs, esteem needs, and self-actualization needs).

Methods

We included older adults aged ≥ 80 years from the 2018 Chinese longitudinal Healthy Longevity Survey (CLHLS). We assessed older people’s subjective wellbeing by their life satisfaction and psychological health. We evaluated four types of intergenerational support: parents provide financial support, receive financial, instrumental and emotional support. We applied binary logistic regression analysis to analyze the association between different intergenerational support and older people’s subjective wellbeing and the moderating effect of self-rated economic status on this relationship.

Results

A total of 8.794 participants were included, with a mean age of 91,46 years (standard deviation:7.60). Older adults who provide financial support (OR: 1.37, 95% CI: 1.01, 1.85) and receive emotional support (OR: 1.99, 95% CI: 1.40, 2.83) report better subjective wellbeing. However, receiving instrumental support depressed psychological health (OR: 0.67, 95% CI: 0.56, 0.79) while improved life satisfaction (OR: 1.42, 95% CI: 1.04, 1.55). Receiving emotional support promoted parents’ psychological health among all combinations of support, and receiving all the three types together raised their subjective wellbeing most.

Conclusions

Our study recognizes that higher level of subjective wellbeing for oldest-old is related to providing financial support, receiving emotional and certain instrumental support. In addition, higher economic status can moderate these associations.
Is deployement of diagnostic test alone enough? Comprehensive package of interventions to strengthen TB laboratory network: three years of experience in Burkina Faso
Authors: Alagna Riccardo , Combary Adjima , Tagliani Elisa , Sawadogo Léon Tinnoga , Saouadogo Tandaogo , Diandé Souba , Ouedraogo Francis , Cirillo Daniela Maria
Published: April 2021

Backgrounds

The laboratory plays a critical role in tuberculosis (TB) control by providing testing for diagnosis, treatment monitoring, and surveillance at each level of the health care system. Weak accessibility to TB diagnosric services still represents a big concern in many limited resources’ countries. Here we report the experience of Burkina Faso in implementing a comprehensive intervention packages to strengthen TB laboratory capacity and diagnostic accessibility.

Methods

The intervention lasted from October 2016 to December 2018 and focused on two main areas: i) development of strategic documents and policies; ii) implementation of TB diagnostic technology.

National TB laboratory data were collected between 2016 and 2018 and evaluated according to five programmatic TB laboratory indicators: i) Percentage of notified new and relapse TB cases with bacteriological confirmation; ii) Percentage of notified new and relapse TB cases tested by Xpert MTB/RIF; iii) Percentage of notified, bacteriologically confirmed TB cases with a drug susceptibility testing (DST) result for rifampin; iv) Percentage of notified MDR-TB cases on the estimated number of MDR-TB cases; v) The ration between the number of smear microscopy and Xpert MTB/RIF tests. We compared these indicators between a 1 year (2016–2017) and 2 years (2016–2018) timeframe.

Results

From 2016 to 2018, the percentage of bacteriologically confirmed cases increased from 67 to 71%. The percentage of new and relapse TB cases notified tested by Xpert MTB/RIF increased from 18% in 2016 to 46% in 2018 and the percentage of bacteriologically confirmed cases with an available DST result for rifampicin increased from 27% in 2016 to 66% in 2018.. The percentage of notified MDR-TB cases on the estimated number of MDR-TB cases in 2018 increased from 43% in 2016 to 78% in 2018. In 2018, the ratio between the number of smear microscopy and Xpert MTB/RIF tests decreased from 53% in 2016 to 21% in 2018.

Conclusion

We demonstrated that the implementation of a comprehensive package of laboratory strengthening interventions led to a significant improvement of all indicators. External technical assistance played a key role in speeding up the TB laboratory system improvement process.
Bronchoalveolar lavage fluid characteristics and outcomes of invasively mechanically ventilated patients with COVID-19 pneumonia in Genoa, Italy
Authors: Dentone Chiara , Vena Antonio , Loconte Maurizio , Grillo Federica , Brunetti Iole , Barisione Emanuela , Tedone Elisabetta , Mora Sara , Di Biagio Antonio , Orsi Andrea , De Maria Andrea , Nicolini Laura , Ball Lorenzo , Giacobbe Daniele Roberto , Magnasco Laura , Delfino Emanuele , Mastracci Luca , Mangerini Rosa , Taramasso Lucia , Sepulcri Chiara , Pincino Rachele , Bavastro Martina , Cerchiaro Matteo , Mikulska Malgorzata , Bruzzone Bianca , Icardi Giancarlo , Frisoni Paolo , Gratarola Angelo , Patroniti Nicolò , Pelosi Paolo , Bassetti Matteo
Published: April 2021

Background

The primary objective of the study is to describe the cellular characteristics of bronchoalveolar lavage fluid (BALF) of COVID-19 patients requiring invasive mechanical ventilation; the secondary outcome is to describe BALF findings between survivors vs non-survivors.

Materials and methods

Patients positive for SARS-CoV-2 RT PCR, admitted to ICU between March and April 2020 were enrolled. At ICU admission, BALF were analyzed by flow cytometry. Univariate, multivariate and Spearman correlation analyses were performed.

Results

Sixty-four patients were enrolled, median age of 64 years (IQR 58–69). The majority cells in the BALF were neutrophils (70%, IQR 37.5–90.5) and macrophages (27%, IQR 7–49) while a minority were lymphocytes, 1%, TCD3+ 92% (IQR 82–95). The ICU mortality was 32.8%. Non-survivors had a significantly older age (p = 0.033) and peripheral lymphocytes (p = 0.012) were lower compared to the survivors. At multivariate analysis the percentage of macrophages in the BALF correlated with poor outcome (OR 1.336, CI95% 1.014–1.759,p = 0.039).

Conclusions

In critically ill patients, BALF cellularity is mainly composed of neutrophils and macrophages. The macrophages percentage in the BALF at ICU admittance correlated with higher ICU mortality. The lack of lymphocytes in BALF could partly explain a reduced anti-viral response.
Leprosy detection rate in patients under immunosuppression for the treatment of dermatological, rheumatological, and gastroenterological diseases: a systematic review of the literature and meta-analysis
Authors: Barroso Daniel Holanda , Brandão Jurema Guerrieri , Andrade Elaine Silva Nascimento , Correia Ana Clara Banhatto , Aquino Danielle Costa , Chen Ana Carolina Rios , Vernal Sebastian , de Araújo Wildo Navegantes , da Mota Lícia Maria Henrique , Sampaio Raimunda Nonata Ribeiro , Kurizky Patrícia Shu , Gomes Ciro Martins
Published: April 2021

Background

Recently developed immunosuppressive drugs, especially TNF antagonists, may enhance the risk of granulomatous infections, including leprosy. We aimed to evaluate the leprosy detection rate in patients under immunosuppression due to rheumatological, dermatological and gastroenterological diseases.

Methods

We performed a systematic review of the literature by searching the PubMed, EMBASE, LILACS, Web of Science and Scielo databases through 2018. No date or language restrictions were applied. We included all articles that reported the occurrence of leprosy in patients under medication-induced immunosuppression.

Results

The search strategy resulted in 15,103 articles; finally, 20 articles were included, with 4 reporting longitudinal designs. The detection rate of leprosy ranged from 0.13 to 116.18 per 100,000 patients/year in the USA and Brazil, respectively. In the meta-analysis, the detection rate of cases of leprosy per 100,000 immunosuppressed patients with rheumatic diseases was 84 (detection rate = 0.00084; 95% CI = 0.0000–0.00266; I2 = 0%, p = 0.55).

Conclusion

Our analysis showed that leprosy was relatively frequently detected in medication-induced immunosuppressed patients suffering from rheumatological diseases, and further studies are needed. The lack of an active search for leprosy in the included articles precluded more precise conclusions.

Trial registration

This review is registered in PROSPERO with the registry number CRD42018116275.
Clinical characteristics, risk factors and outcome of severe Norovirus infection in kidney transplant patients: a case-control study
Authors: Gras Julien , Abdel-Nabey Moustafa , Dupont Axelle , Le Goff Jérôme , Molina Jean-Michel , Peraldi Marie Noëlle
Published: April 2021

Background

Human Norovirus (HuNoV) has recently been identified as a major cause of diarrhea among kidney transplant recipients (KTR). Data regarding risk factors associated with the occurrence of HuNoV infection, and its long-term impact on kidney function are lacking.

Methods

We conducted a retrospective case-control study including all KTR with a diagnosis of HuNoV diarrhea. Each case was matched to a single control according to age and date of transplantation, randomly selected among our KTR cohort and who did not develop HuNoV infection. Risk factors associated with HuNoV infection were identified using conditional logistic regression, and survival was estimated using Kaplan-Meier estimator.

Results

From January 2012 to April 2018, 72 cases of NoV diarrhea were identified among 985 new KT, leading to a prevalence of HuNoV infection of 7.3%. Median time between kidney transplantation and diagnosis was 46.5 months (Inter Quartile Range [IQR]:17.8–81.5), and the median duration of symptoms 40 days (IQR: 15–66.2). Following diagnosis, 93% of the cases had a reduction of immunosuppression. During follow-up, de novo Donor Specific Antibody (DSA) were observed in 8 (9%) cases but none of the controls (p = 0.01). Acute rejection episodes were significantly more frequent among cases (13.8% versus 4.2% in controls; p = 0,03), but there was no difference in serum creatinine level at last follow-up between the two groups (p = 0.08). Pre-transplant diabetes and lymphopenia below 1000/mm3 were identified as risks factors for HuNoV infection in multivariate analysis.

Conclusion

HuNoV infection is a late-onset and prolonged infection among KTR. The current management, based on the reduction of immunosuppressive treatment, is responsible for the appearance of de novo DSA and an increase in acute rejection episodes.
Determinants of willingness to accept kidney transplantation among chronic kidney disease patients in Ghana
Authors: Boima V. , Amissah-Arthur M. B. , Yorke E. , Dey D. , Fiagbe Delali , Yawson A. E. , Nonvignon J. , Mate-Kole C. C.
Published: April 2021

Background

The burden of chronic kidney disease in Africa is three to four times higher compared to high-income countries and the cost of treatment is beyond the reach of most affected persons. The best treatment for end stage renal disease is kidney transplantation which is not available in most African countries. As kidney transplantation surgery is emerging in Ghana, this study assessed factors which could influence the willingness of patients with chronic kidney disease to accept it as a mode of treatment.

Methods

This cross-sectional survey was carried out among patients with chronic kidney disease in Korle-Bu Teaching Hospital. A consecutive sampling method was used to recruit consenting patients. A structured questionnaire and standardized research instruments were used to obtain information on demographic, socio-economic characteristics, knowledge about transplantation, perception of transplantation, religiosity and spirituality. Logistic regression model was used to assess the determinants of willingness to accept a kidney transplant.

Results

342 CKD patients participated in the study of which 56.7% (n = 194) were male. The mean age of the participants was 50.24 ± 17.08 years. The proportion of participants who were willing to accept a kidney transplant was 67.3% (95%CI: 62.0–72.2%). The factors which influenced participants’ willingness to accept this treatment included; willingness to attend a class on kidney transplantation (p < 0.016), willingness to donate a kidney if they had the chance (p < 0.005), perception that a living person could donate a kidney (p < 0.001) and perceived improvement in quality of life after transplantation (p < 0.005). The barriers for accepting kidney transplantation were anticipated complications of transplant surgery and financial constraints.

Conclusion

More than two-thirds of CKD patients were willing to accept a kidney transplant and this is influenced by multiple factors. Government health agencies must consider full or partial coverage of kidney transplantation through the existing national health insurance scheme. Further, efficient educational programmes are required to improve both patients’ and physicians’ knowledge on the importance of kidney transplantation in the management of end stage renal disease in Ghana.
Acute motor and sensory axonal neuropathy in association with primary Sjögren’s syndrome: a case report
Authors: Chen Yu-Ming , Su Kuei-Ying
Published: April 2021

Background

Primary Sjögren’s syndrome is a chronic, autoimmune, connective tissue disorder that results from the infiltration of exocrine glands, especially the lacrimal and salivary glands, by autoantibodies. Patients with Sjögren’s syndrome commonly present with dry eyes (xerophthalmia) and dry mouth (xerostomia). However, the clinical manifestations of Sjögren’s syndrome can be complicated and variable due to involvement of extraglandular organ systems, such as the nervous system. The neurological manifestations of this disorder often precede those of other exocrine gland symptoms. Hence, early diagnosis of Sjögren’s syndrome remains a challenge.

Case presentation

We report the case of a 63-year-old woman with primary Sjögren’s syndrome who presented with acute motor and sensory axonal neuropathy (AMSAN). Treatment with glucocorticoids and immunosuppressants partially improved her muscle weakness and paresthesia.

Conclusions

This case demonstrates the importance of early recognition and diagnosis of AMSAN in association with primary Sjögren’s syndrome to achieve a favorable clinical outcome. Primary Sjögren’s syndrome may be underdiagnosed because of vague symptoms of the sicca complex. Comprehensive immunological testing to evaluate this condition may be performed in patients presenting with variants of Guillain-Barré syndrome.
Implementation of a first-trimester prognostic model to improve screening for gestational diabetes mellitus
Authors:   On behalf of the RESPECT 2 study group, van Hoorn Fieke , Koster Maria P. H. , Kwee Anneke , Groenendaal Floris , Franx Arie , Bekker Mireille N.
Published: April 2021

Background

Improvement in the accuracy of identifying women who are at risk to develop gestational diabetes mellitus (GDM) is warranted, since timely diagnosis and treatment improves the outcomes of this common pregnancy disorder. Although prognostic models for GDM are externally validated and outperform current risk factor based selective approaches, there is little known about the impact of such models in day-to-day obstetric care.

Methods

A prognostic model was implemented as a directive clinical prediction rule, classifying women as low- or high-risk for GDM, with subsequent distinctive care pathways including selective midpregnancy testing for GDM in high-risk women in a prospective multicenter birth cohort comprising 1073 pregnant women without pre-existing diabetes and 60 obstetric healthcare professionals included in nine independent midwifery practices and three hospitals in the Netherlands (effectiveness-implementation hybrid type 2 study). Model performance (c-statistic) and implementation outcomes (acceptability, adoption, appropriateness, feasibility, fidelity, penetration, sustainability) were evaluated after 6 months by indicators and implementation instruments (NoMAD; MIDI).

Results

The adherence to the prognostic model (c-statistic 0.85 (95%CI 0.81–0.90)) was 95% (n = 1021). Healthcare professionals scored 3.7 (IQR 3.3–4.0) on implementation instruments on a 5-point Likert scale. Important facilitators were knowledge, willingness and confidence to use the model, client cooperation and opportunities for reconfiguration. Identified barriers mostly related to operational and organizational issues. Regardless of risk-status, pregnant women appreciated first-trimester information on GDM risk-status and lifestyle advice to achieve risk reduction, respectively 89% (n = 556) and 90% (n = 564)).

Conclusions

The prognostic model was successfully implemented and well received by healthcare professionals and pregnant women. Prognostic models should be recommended for adoption in guidelines.
Carnitine palmitoyl transferase 1A is a novel diagnostic and predictive biomarker for breast cancer
Authors: Tan Zheqiong , Zou Yaru , Zhu Man , Luo Zhenzhao , Wu Tangwei , Zheng Chao , Xie Aqing , Wang Hui , Fang Shiqiang , Liu Shuiyi , Li Yong , Lu Zhongxin
Published: April 2021

Background

Carnitine palmitoyl transferase 1A (CPT1A), the key regulator of fatty acid oxidation, contributes to tumor metastasis and therapeutic resistance. We aimed to identify its clinical significance as a biomarker for the diagnosis and prediction of breast cancer.

Methods

Western blot, ELISA and in silico analysis were used to confirm CPT1A levels in breast cancer cell lines, cell culture medium and breast cancer tissues. Four hundred thirty breast cancer patients, 200 patients with benign breast disease, and 400 healthy controls were enrolled and randomly divided into a training set and a test set with a 7:3 ratio. Training set was used to build diagnostic models and 10-fold cross validation was used to demonstrate the performance of the models. Then test set was aimed to validate the effectiveness of the diagnostic models. ELISA was conducted to detect individual serum CPT1A levels. Receiver operating characteristic (ROC) curves were generated, and binary logistic regression analyses were performed to evaluate the effectiveness of CPT1A as a biomarker in breast cancer diagnosis. CPT1A levels between post-operative and pre-operative samples were also compared.

Results

CPT1A was overexpressed in breast cancer tissues, cell lines and cell culture medium. Serum CPT1A levels were higher in breast cancer patients than in controls and were significantly associated with metastasis, TNM stage, histological grading and molecular subtype. CPT1A levels were decreased in post-operative samples compared with paired pre-operative samples. Moreover, CPT1A exhibited a higher efficacy in differentiating breast cancer patients from healthy controls (training set: area under the curve, AUC, 0.892, 95% CI, 0.872–0.920; test set, AUC, 0.904, 95% CI, 0.869–0.939) than did CA15–3, CEA, or CA125.

Conclusion

CPT1A is overexpressed in breast cancer and can be secreted out of breast cancer cell. Serum CPT1A is positively associated with breast cancer progression and could serve as an indicator for disease monitoring. Serum CPT1A displayed a remarkably high diagnostic efficiency for breast cancer and could be a novel biomarker for the diagnosis of breast cancer.
Role of palliative radiotherapy in bleeding control in patients with unresectable advanced gastric cancer
Authors: Yu Jesang , Jung Jinhong , Park Sook Ryun , Ryu Min-Hee , Park Jin-hong , Kim Jong Hoon , Yoon Sang Min
Published: April 2021

Background

This study analyzed the clinical results of palliative radiotherapy for bleeding control in patients with unresectable advanced gastric cancer.

Methods

We retrospectively reviewed the medical records of patients who met the following inclusion criteria between January 2002 and June 2018: histologically proven gastric cancer, gastric tumor bleeding confirmed by upper gastrointestinal endoscopy, and palliative radiotherapy performed for hemostasis. The median radiotherapy dose was 30 Gy, with a daily dose ranging from 1.8 to 3 Gy.

Results

Sixty-one patients were included in this analysis. The study population was predominantly male (72.1%), with a median age of 62 years (range: 32–92). The median baseline hemoglobin level was 7.1 g/dL, and the most common presenting symptom of gastric tumor bleeding was melena (85.2%). Bleeding control was achieved in 54 (88.5%) patients. The median levels of hemoglobin at 1, 2, and 3 months after completion of radiotherapy were 10.1 g/dL, 10.2 g/dL, and 10.4 g/dL, respectively; these values were significantly different from that before radiotherapy (7.1 g/dL; p < 0.001). The median overall survival was 4.8 months. Among the 54 patients who achieved bleeding control after radiotherapy, 19 (35.2%) experienced re-bleeding during the follow-up period. The median time to re-bleeding was 6.0 months. Multivariate analysis demonstrated that a higher radiation dose (p = 0.007) and additional chemotherapy after radiotherapy (p = 0.004) were significant factors for prolonging the time to re-bleeding.

Conclusions

Tumor bleeding was adequately controlled by radiotherapy in patients with unresectable advanced gastric cancer.
The mediation effect of serum metabolites on the relationship between long-term smoking exposure and esophageal squamous cell carcinoma
Authors: Wei Mengke , Zhao Lihong , Lv Jiali , Li Xia , Zhou Guangshuai , Fan Bingbing , Shen Xiaotao , Zhao Deli , Xue Fuzhong , Wang Jialin , Zhang Tao
Published: April 2021

Background

Long-term smoking exposure will increase the risk of esophageal squamous cell carcinoma (ESCC), whereas the mechanism is still unclear. We conducted a cross-sectional study to explore whether serum metabolites mediate the occurrence of ESCC caused by cigarette smoking.

Methods

Serum metabolic profiles and lifestyle information of 464 participants were analyzed. Multiple logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of smoking exposure to ESCC risk. High-dimensional mediation analysis and univariate mediation analysis were performed to screen potential intermediate metabolites of smoking exposure for ESCC.

Results

Ever smoking was associated with a 3.11-fold increase of ESCC risk (OR = 3.11, 95% CI 1.63–6.05), and for each cigarette-years increase in smoking index, ESCC risk increased by 56% (OR = 1.56, 95% CI 1.18–2.13). A total of 5 metabolites were screened as mediators by high-dimensional mediation analysis. In addition, glutamine, histidine, and cholic acid were further proved existing mediation effects according to univariate mediation analysis. And the proportions of mediation of histidine and glutamine were 40.47 and 30.00%, respectively. The mediation effect of cholic acid was 8.98% according to the analysis of smoking index.

Conclusions

Our findings suggest that cigarette smoking contributed to incident ESCC, which may be mediated by glutamine, histidine and cholic acid.