bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical microscopy reveals the dynamic nature of B. pseudomallei morphology during β-lactam antimicrobial susceptibility testing
Authors: McLaughlin Heather P. , Bugrysheva Julia , Sue David
Published: July 2020

Background

In Gram-negative species, β-lactam antibiotics target penicillin binding proteins (PBPs) resulting in morphological alterations of bacterial cells. Observations of antibiotic-induced cell morphology changes can rapidly and accurately differentiate drug susceptible from resistant bacterial strains; however, resistant cells do not always remain unchanged. Burkholderia pseudomallei is a Gram-negative, biothreat pathogen and the causative agent of melioidosis, an often fatal infectious disease for humans.

Results

Here, we identified β-lactam targets in B. pseudomallei by in silico analysis. Ten genes encoding putative PBPs, including PBP-1, PBP-2, PBP-3 and PBP-6, were detected in the genomes of susceptible and resistant strains. Real-time, live-cell imaging of B. pseudomallei strains demonstrated dynamic morphological changes in broth containing clinically relevant β-lactam antibiotics. At sub-inhibitory concentrations of ceftazidime (CAZ), amoxicillin-clavulanic acid (AMC), and imipenem (IPM), filamentation, varying in length and proportion, was an initial response of the multidrug-resistant strain Bp1651 in exponential phase. However, a dominant morphotype reemerged during stationary phase that resembled cells unexposed to antibiotics. Similar morphology dynamics were observed for AMC-resistant strains, MSHR1655 and 724644, when exposed to sub-inhibitory concentrations of AMC. For all B. pseudomallei strains evaluated, increased exposure time and exposure to increased concentrations of AMC at and above minimal inhibitory concentrations (MICs) in broth resulted in cell morphology shifts from filaments to spheroplasts and/or cell lysis. B. pseudomallei morphology changes were more consistent in IPM. Spheroplast formation followed by cell lysis was observed for all strains in broth containing IPM at concentrations greater than or equal to MICs, however, the time to cell lysis was variable. B. pseudomallei cell lengths were strain-, drug- and drug concentration-dependent.

Conclusions

Both resistant and susceptible B. pseudomallei strains exhibited filamentation during early exposure to AMC and CAZ at concentrations used to interpret susceptibility (based on CLSI guidelines). While developing a rapid β-lactam antimicrobial susceptibility test based on cell-shape alone requires more extensive analyses, optical microscopy detected B. pseudomallei growth attributes that lend insight into antibiotic response and antibacterial mechanisms of action.
Occurrence, virulence genes, and antimicrobial profiles of Escherichia coli O157 isolated from ruminants slaughtered in Al Ain, United Arab Emirates
Authors: Al-Ajmi Dawood , Rahman Shafeeq , Banu Sharmila
Published: July 2020

Background

Shiga toxin-producing Escherichia coli (STEC) is a major source of food-borne illness around the world. E. coli O157 has been widely reported as the most common STEC serogroup and has emerged as an important enteric pathogen. Cattle, in particular have been identified as a major E. coli O157:H7 reservoir of human infections; however, the prevalence of this organism in camels, sheep, and goats is less understood. The aim of this study was to evaluate the occurrence and concentration of E. coli serotype O157 in the feces of healthy camels (n = 140), cattle (n = 137), sheep (n = 141) and goats (n = 150) slaughtered in United Arab Emirates (UAE) for meat consumption between September 2017 and August 2018. We used immunomagnetic separation coupled with a culture-plating method to detect E. coli O157. Non-sorbitol fermenting colonies were assessed via latex-agglutination testing, and positive cultures were analyzed by performing polymerase chain reactions to detect genes encoding attaching and effacing protein (eaeA), hemolysin A (hlyA, also known as ehxA) and Shiga toxin (stx1 and stx2), and E. coli O157:H7 specific genes (rfb O157, uidA, and fliC). All E. coli O157 isolates were analyzed for their susceptibility to 20 selected antimicrobials.

Results

E. coli O157 was observed in camels, goats, and cattle fecal samples at abundances of 4.3, 2, and 1.46%, respectively, but it was undetectable in sheep feces. The most prevalent E. coli O157 gene in all STEC isolates was stx2;, whereas, stx1 was not detected in any of the samples. The fecal samples from camels, goats, and cattle harbored E. coli O157 isolates that were 100% susceptible to cefotaxime, chloramphenicol, ciprofloxacin, norfloxacin, and polymyxin B.

Conclusion

To our knowledge, this is the first report on the occurrence of E. coli O157 in slaughter animals in the UAE. Our results clearly demonstrate the presence of E. coli O157 in slaughtered animals, which could possibly contaminate meat products intended for human consumption.
Transcriptome analysis reveals ethylene-mediated defense responses to Fusarium oxysporum f. sp. cucumerinum infection in Cucumis sativus L.
Authors: Dong Jingping , Wang Yuean , Xian Qianqian , Chen Xuehao , Xu Jun
Published: July 2020

Background

Fusarium wilt, caused by Fusarium oxysporum f. sp. cucumerinum (Foc), is a severe disease affecting cucumber (Cucumis sativus L.) production worldwide, but mechanisms underlying Fusarium wilt resistance in cucumber remain unknown. To better understand of the defense mechanisms elicited in response to Foc inoculation, RNA sequencing-based transcriptomic profiling of responses of the Fusarium wilt-resistant cucumber line ‘Rijiecheng’ at 0, 24, 48, 96, and 192 h after Foc inoculation was performed.

Results

We identified 4116 genes that were differentially expressed between 0 h and other time points after inoculation. All ethylene-related and pathogenesis-related genes from the differentially expressed genes were filtered out. Real-time PCR analysis showed that ethylene-related genes were induced in response to Foc infection. Importantly, after Foc infection and exogenous application of ethephon, a donor of ethylene, the ethylene-related genes were highly expressed. In response to exogenous ethephon treatment in conjunction with Foc inoculation, the infection resistance of cucumber seedlings was enhanced and endogenous ethylene biosynthesis increased dramatically.

Conclusion

Collectively, ethylene signaling pathways play a positive role in regulating the defense response of cucumber to Foc infection. The results provide insight into the cucumber Fusarium wilt defense mechanisms and provide valuable information for breeding new cucumber cultivars with enhanced Fusarium wilt tolerance.
Transcriptomic analysis of flower opening response to relatively low temperatures in Osmanthus fragrans
Authors: Fu Jianxin , Zhang Chao , Liu Yucheng , Pang Tianhong , Dong Bin , Gao Xiaoyue , Zhu Yimin , Zhao Hongbo
Published: July 2020

Background

Sweet osmanthus (Osmanthus fragrans Lour.) is one of the top ten traditional ornamental flowers in China. The flowering time of once-flowering cultivars in O. fragrans is greatly affected by the relatively low temperature, but there are few reports on its molecular mechanism to date. A hypothesis had been raised that genes related with flower opening might be up-regulated in response to relatively low temperature in O. fragrans. Thus, our work was aimed to explore the underlying molecular mechanism of flower opening regulated by relatively low temperature in O. fragrans.

Results

The cell size of adaxial and abaxial petal epidermal cells and ultrastructural morphology of petal cells at different developmental stages were observed. The cell size of adaxial and abaxial petal epidermal cells increased gradually with the process of flower opening. Then the transcriptomic sequencing was employed to analyze the differentially expressed genes (DEGs) under different number of days’ treatments with relatively low temperatures (19 °C) or 23 °C. Analysis of DEGs in Gene Ontology analysis showed that “metabolic process”, “cellular process”, “binding”, “catalytic activity”, “cell”, “cell part”, “membrane”, “membrane part”, “single-organism process”, and “organelle” were highly enriched. In KEGG analysis, “metabolic pathways”, “biosynthesis of secondary metabolites”, “plant-pathogen interaction”, “starch and sucrose metabolism”, and “plant hormone signal transduction” were the top five pathways containing the greatest number of DEGs. The DEGs involved in cell wall metabolism, phytohormone signal transduction pathways, and eight kinds of transcription factors were analyzed in depth.

Conclusions

Several unigenes involved in cell wall metabolism, phytohormone signal transduction pathway, and transcription factors with highly variable expression levels between different temperature treatments may be involved in petal cell expansion during flower opening process in response to the relatively low temperature. These results could improve our understanding of the molecular mechanism of relatively-low-temperature-regulated flower opening of O. fragrans, provide practical information for the prediction and regulation of flowering time in O. fragrans, and ultimately pave the way for genetic modification in O. fragrans.
Modeling adaptive response profiles in a vaccine clinical trial
Authors: Hasdemir Dicle , van den Berg Robert A. , van Kampen Antoine , Smilde Age K.
Published: July 2020

Background

Vaccine clinical studies typically provide time-resolved data on adaptive response read-outs in response to the administration of that particular vaccine to a cohort of individuals. However, modeling such data is challenged by the properties of these time-resolved profiles such as non-linearity, scarcity of measurement points, scheduling of the vaccine at multiple time points. Linear Mixed Models (LMM) are often used for the analysis of longitudinal data but their use in these time-resolved immunological data is not common yet. Apart from the modeling challenges mentioned earlier, selection of the optimal model by using information-criterion-based measures is far from being straight-forward. The aim of this study is to provide guidelines for the application and selection of LMMs that deal with the challenging characteristics of the typical data sets in the field of vaccine clinical studies.

Methods

We used antibody measurements in response to Hepatitis-B vaccine with five different adjuvant formulations for demonstration purposes. We built piecewise-linear, piecewise-quadratic and cubic models with transformations of the axes with pre-selected or optimized knot locations where time is a numerical variable. We also investigated models where time is categorical and random effects are shared intercepts between different measurement points. We compared all models by using Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), Deviance Information Criterion (DIC), variations of conditional AIC and by visual inspection of the model fit in the light of prior biological information.

Results

There are various ways of dealing with the challenges of the data which have their own advantages and disadvantages. We explain these in detail here. Traditional information-criteria-based measures work well for the coarse selection of the model structure and complexity, however are not efficient at fine tuning of the complexity level of the random effects.

Conclusions

We show that common statistical measures for optimal model complexity are not sufficient. Rather, explicitly accounting for model purpose and biological interpretation is needed to arrive at relevant models.

Trial Registration

Clinical trial registration number for this study: NCT00805389, date of registration: December 9, 2008 (pro-active registration).
Non-inferiority comparative clinical trial between early oral REFEEDING and usual oral REFEEDING in predicted mild acute biliary pancreatitis
Authors: Lozada-Hernández Edgard Efrén , Barrón-González Omar , Vázquez-Romero Santa , Cano-Rosas Martin , Apolinar-Jimenez Evelia
Published: July 2020

Background

The aim of the study was to compare the onset of oral feeding in the first 24 h after hospital admission with usual oral refeeding and determine whether the timing of the onset of oral feeding influences the recurrence of pain or alters the blood levels of pancreatic enzymes in patients with predicted mild acute biliary pancreatitis.

Methods

This non-inferiority randomized controlled trial was carried out between September 2018 and June 2019 after receiving authorization from the ethics committee for health research. Patients with a diagnosis of predicted mild acute biliary pancreatitis were divided into Group A (early oral refeeding, EOR) and Group B (usual oral refeeding, UOR). Outcome measures included pancreatic lipase levels, the systemic inflammatory response (concentrations of leukocytes), feasibility (evaluated by abdominal pain recurrence), the presence and recurrence of gastrointestinal symptoms and the length of hospital stay.

Results

Two patients in the EOR group experienced pain relapse (3.2%), and four patients in the UOR group experienced pain relapse (6.77%) after oral refeeding (p = 0.379). The presence of nausea or vomiting after the onset of oral refeeding was not different between the two groups (p = 0.293). The onset of oral refeeding was approximately 48 h later in the UOR group. The length of hospital stay was 5 days in the EOR group and 8 days in the UOR group (p = 0.042), and this difference was also manifested in higher hospital costs in the UOR group (p = 0.0235).

Conclusion

Compared with usual oral refeeding, early oral refeeding is safe in predicted mild acute biliary pancreatitis patients, does not cause adverse gastrointestinal events, and reduces the length of hospital stay and costs.

Trial registration

Early oral refeeding in mild acute pancreatitis (EORVsUOR). NCT04168801, retrospectively registered (November 19, 2019).
Predictive factors for positive disco-vertebral biopsy culture in pyogenic vertebral osteomyelitis, and impact of fluoroscopic versus scanographic guidance
Authors: Diffre Caroline , Jousset Camille , Roux Anne-Laure , Duran Clara , Noussair Latifa , Rottman Martin , Carlier Robert-Yves , Dinh Aurélien
Published: July 2020

Background

The aims of this study were to identify the predictive factors for microbiological diagnosis through disco-vertebral biopsy (DVB) in patients with pyogenic vertebral osteomyelitis (PVO) and negative blood cultures, and compare the performance of DVB under fluoroscopic versus scanographic guidance.

Methods

We performed a cohort study comparing positive and negative DVB among patients with PVO. All cases of PVO undergoing a DVB for microbiological diagnosis in our center were retrospectively reviewed. Infections due to Mycobacterium tuberculosis, infections on foreign device, and non-septic diseases were excluded. Anamnestic, clinical, biological, microbiological, as well as radiological data were collected from medical charts thanks to a standardized data set.

Results

A total of 111 patients were screened; 88 patients were included. Microbiological cultures were positive in 53/88 (60.2%) patients. A thickening of the paravertebral tissue ≥10 mm on magnetic resonance imaging (MRI) in axial MR scans was a predictive factor of DVB microbiological positivity (52.4% vs. 13.3%; p = 0.006; OR = 5.4). Overall, 51 DVB were performed under fluoroscopic guidance and 37 under scanographic guidance. Considering lumbar DVB, 25/36 (69.4%) of cases yielded positive results under fluoroscopic guidance versus 5/15 (33.3%) under scanographic guidance (p = 0.02; OR = 4.4). No adverse event linked to DVB was notified.

Conclusion

Every patient with PVO and negative blood cultures should undergo a DVB. A thickening of the paravertebral tissue ≥10 mm on MRI is associated with a higher rate of positive DVB culture. A lumbar DVB under fluoroscopic guidance is more sensitive than under scanographic guidance to identify the micro-organism involved.
The WOMAN trial: clinical and contextual factors surrounding the deaths of 483 women following post-partum haemorrhage in developing countries
Authors: Picetti Roberto , Miller Lori , Shakur-Still Haleema , Pepple Tracey , Beaumont Danielle , Balogun Eni , Asonganyi Etienne , Chaudhri Rizwana , El-Sheikh Mohamed , Vwalika Bellington , Arulkumaran Sabaratnam , Roberts Ian ,   on behalf of the WOMAN trial collaborators
Published: July 2020

Background

Post-partum haemorrhage (PPH) is a leading cause of maternal death worldwide. The WOMAN trial assessed the effects of tranexamic acid (TXA) on death and surgical morbidity in women with PPH. The trial recorded 483 maternal deaths. We report the circumstances of the women who died.

Methods

The WOMAN trial recruited 20,060 women with a clinical diagnosis of PPH after a vaginal birth or caesarean section. We randomly allocated women to receive TXA or placebo. When a woman died, we asked participating clinicians to report the cause of death and to provide a short narrative of the events surrounding the death. We collated and edited for clarity the narrative data.

Results

Case fatality rates were 3.0% in Africa and 1.7% in Asia. Nearly three quarters of deaths were within 3 h of delivery and 91% of these deaths were from bleeding. Women who delivered outside a participating hospital (12%) were three times more likely to die (OR = 3.12, 95%CI 2.55–3.81) than those who delivered in hospital. Blood was often unavailable due to shortages or because relatives could not afford to buy it. Clinicians highlighted late presentation, maternal anaemia and poor infrastructure as key contributory factors.

Conclusions

Although TXA use reduces bleeding deaths by almost one third, mortality rates similar to those in high income countries will not be achieved without tackling late presentation, maternal anaemia, availability of blood for transfusion and poor infrastructure.
Transcriptomic insight into salinomycin mechanisms in breast cancer cell lines: synergistic effects with dasatinib and induction of estrogen receptor β
Authors: Bellat Vanessa , Verchère Alice , Ashe Sally A. , Law Benedict
Published: July 2020

Background

Tumors are heterogeneous in nature, composed of different cell populations with various mutations and/or phenotypes. Using a single drug to encounter cancer progression is generally ineffective. To improve the treatment outcome, multiple drugs of distinctive mechanisms but complementary anticancer activities (combination therapy) are often used to enhance antitumor efficacy and minimize the risk of acquiring drug resistance. We report here the synergistic effects of salinomycin (a polyether antibiotic) and dasatinib (a Src kinase inhibitor).

Methods

Functionally, both drugs induce cell cycle arrest, intracellular reactive oxygen species (iROS) production, and apoptosis. We rationalized that an overlapping of the drug activities should offer an enhanced anticancer effect, either through vertical inhibition of the Src-STAT3 axis or horizontal suppression of multiple pathways. We determined the toxicity induced by the drug combination and studied the kinetics of iROS production by fluorescence imaging and flow cytometry. Using genomic and proteomic techniques, including RNA-sequencing (RNA-seq), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western Blot, we subsequently identified the responsible pathways that contributed to the synergistic effects of the drug combination.

Results

Compared to either drug alone, the drug combination showed enhanced potency against MDA-MB-468, MDA-MB-231, and MCF-7 human breast cancer (BC) cell lines and tumor spheroids. The drug combination induces both iROS generation and apoptosis in a time-dependent manner, following a 2-step kinetic profile. RNA-seq data revealed that the drug combination exhibited synergism through horizontal suppression of multiple pathways, possibly through a promotion of cell cycle arrest at the G1/S phase via the estrogen-mediated S-phase entry pathway, and partially via the BRCA1 and DNA damage response pathway.

Conclusion

Transcriptomic analyses revealed for the first time, that the estrogen-mediated S-phase entry pathway partially contributed to the synergistic effect of the drug combination. More importantly, our studies led to the discoveries of new potential therapeutic targets, such as E2F2, as well as a novel drug-induced targeting of estrogen receptor β (ESR2) approach for triple-negative breast cancer treatment, currently lacking of targeted therapies.
Atypical anterior persistent hyperplastic primary vitreous: report of a rare case
Authors: Wang Jue , Yan Hong , Du Zhaojiang , Zhang Jie , Wang Weinong , Guo Chenjun
Published: July 2020

Background

Persistent hyperplastic primary vitreous (PHPV) is a congenital form of vitreous dysplasia that can be categorized into anterior, posterior, and mixed types according to the affected location within the eye. Definitive diagnoses of PHPV are usually made based on B-mode ultrasound, optical coherence tomography (OCT), and Doppler ultrasound findings. In this report, we discuss the case of a 7-year-old boy in whom a definitive diagnosis of atypical anterior PHPV was possible based on intraoperative observations, pathological findings, and the results of ophthalmic examination.

Case presentation

A 7-year-old boy presented with leukocoria and acute glaucoma in his right eye. Imaging suggested characteristics of mixed PHPV. Surgical treatment and pathological examination were performed due to the presence of acute glaucoma and abnormal lens morphology. Typical signs of posterior PHPV (e.g., eyeball shrinkage, the presence of vascular membranes connected to the optic disc, etc.) were not observed. However, there were abundant fibrous vascular membranes around the lens. Pathological examination revealed fibrocyte proliferation in the lens and capsular tissue. Intraoperative findings were used in conjunction with the results of pathological and ophthalmological examinations to make the final diagnosis of anterior PHPV.

Conclusion

The course and characteristics of PHPV can be unpredictable, and it is often the case that a clear diagnosis cannot be obtained based on clinical characteristics and typical imaging examinations alone. Further surgical treatment and pathological examination may aid in establishing a final diagnosis. In addition to treating the complications of PHPV (e.g., glaucoma), surgery may improve eye appearance and restore visual function to some degree.
Development and validation of new figural scales for female body dissatisfaction assessment on two dimensions: thin-ideal and muscularity-ideal
Authors: Ralph-Nearman Christina , Filik Ruth
Published: July 2020

Background

Body dissatisfaction influences women’s mental and physical health. To date, most research has focused on body dissatisfaction in relation to the ‘thin-ideal’. Thus, the association between body dissatisfaction, eating disorder symptomatology and muscularity-ideal in women is less clear. Lack of understanding is underpinned by the lack of reliable and valid muscularity-related assessments for women. To address this need, we developed, tested and re-tested two new body dissatisfaction scales: The Female Body Scale (FBS; adiposity dimension) and Female Fit Body Scale (FFITBS; muscularity dimension).

Methods

One hundred and fifty-two women in the United Kingdom rated which body figure best represented their current and ideal body, completed the Eating Disorder Examination Questionnaire (EDE-Q 6.0), and their body composition was measured. During re-test, the EDE-Q 6.0 and Drive for Muscularity Scale (DMS) were completed.

Results

Both the FBS and the FFITBS were found to be valid and reliable, and distinct types of body dissatisfaction were identified. Higher EDE-Q scores corresponded with greater body dissatisfaction scores on both the FBS and FFITBS. Thin-ideal (FBS) and larger/muscularity-ideal (FFITBS) body dissatisfaction predicted higher scores on the DMS. The muscularity scale (FFITBS) uniquely revealed that 28% of participants indicated body dissatisfaction toward the larger-muscularity-ideal.

Conclusions

Results reveal distinct dimensions of body dissatisfaction. These new, validated scales may be utilized to quickly identify eating disorder risk in women as a preventative assessment for clinicians and inform female-focused body-image and eating disorder research.
Integrated Management of Childhood Illnesses implementation-related factors at 18 Colombian cities
Authors: García Sierra Andrés Mauricio , Ocampo Cañas Jovana Alexandra
Published: July 2020

Background

Integrated Management of Childhood Illnesses (IMCI) is a strategy developed by the World Health Organization (WHO) and UNICEF in 1992. It was deployed as an integrated approach to improve children’s health in the world. This strategy is divided into three components: organizational, clinical, and communitarian. If the Integrated Management of Childhood Illnesses implementation-related factors in low- and middle-income countries are known, the likelihood of decreasing infant morbidity and mortality rates could be increased. This work aimed to identify, from the clinical component of the strategy, the implementation-related factors to Integrated Management of Childhood Illnesses at 18 Colombian cities.

Methods

A quantitative cross-sectional study was performed with a secondary analysis of databases of a study conducted in Colombia by the Public Health group of Universidad de Los Andes in 2016. An Integrated Care Index was calculated as a dependent variable and descriptive bivariate and multivariate analyses to find the relationship between this index and the relevant variables from literature.

Results

Information was obtained from 165 medical appointments made by nurses, general practitioners, and pediatricians. Health access is given mainly in the urban area, in the first level care and outpatient context. Essential medicines availability, necessary supplies, second-level care, medical appointment periods longer than 30 min, and care to the child under 30 months are often related to higher rates of Integrated Care Index.

Conclusion

Health care provided to children under five remains incomplete because it does not present the basic minimums for the adequate IMCI’s implementation in the country. It is necessary to provide integrated care that provides medicine availability and essential supplies that reduce access barriers and improve the system’s fragmentation.
A cross-omics integrative study of metabolic signatures of chronic obstructive pulmonary disease
Authors: Prokić Ivana , Lahousse Lies , de Vries Maaike , Liu Jun , Kalaoja Marita , Vonk Judith M. , van der Plaat Diana A. , van Diemen Cleo C. , van der Spek Ashley , Zhernakova Alexandra , Fu Jingyuan , Ghanbari Mohsen , Ala-Korpela Mika , Kettunen Johannes , Havulinna Aki S. , Perola Markus , Salomaa Veikko , Lind Lars , Ärnlöv Johan , Stricker Bruno H. C. , Brusselle Guy G. , Boezen H. Marike , van Duijn Cornelia M. , Amin Najaf
Published: July 2020

Background

Chronic obstructive pulmonary disease (COPD) is a common lung disorder characterized by persistent and progressive airflow limitation as well as systemic changes. Metabolic changes in blood may help detect COPD in an earlier stage and predict prognosis.

Methods

We conducted a comprehensive study of circulating metabolites, measured by proton Nuclear Magnetic Resonance Spectroscopy, in relation with COPD and lung function. The discovery sample consisted of 5557 individuals from two large population-based studies in the Netherlands, the Rotterdam Study and the Erasmus Rucphen Family study. Significant findings were replicated in 12,205 individuals from the Lifelines-DEEP study, FINRISK and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) studies. For replicated metabolites further investigation of causality was performed, utilizing genetics in the Mendelian randomization approach.

Results

There were 602 cases of COPD and 4955 controls used in the discovery meta-analysis. Our logistic regression results showed that higher levels of plasma Glycoprotein acetyls (GlycA) are significantly associated with COPD (OR = 1.16, P = 5.6 × 10− 4 in the discovery and OR = 1.30, P = 1.8 × 10− 6 in the replication sample). A bi-directional two-sample Mendelian randomization analysis suggested that circulating blood GlycA is not causally related to COPD, but that COPD causally increases GlycA levels. Using the prospective data of the same sample of Rotterdam Study in Cox-regression, we show that the circulating GlycA level is a predictive biomarker of COPD incidence (HR = 1.99, 95%CI 1.52–2.60, comparing those in the highest and lowest quartile of GlycA) but is not significantly associated with mortality in COPD patients (HR = 1.07, 95%CI 0.94–1.20).

Conclusions

Our study shows that circulating blood GlycA is a biomarker of early COPD pathology.
Specific manifestations of knee osteoarthritis predict depression and anxiety years in the future: Vancouver Longitudinal Study of Early Knee Osteoarthritis
Authors: Sayre Eric C. , Esdaile John M. , Kopec Jacek A. , Singer Joel , Wong Hubert , Thorne Anona , Guermazi Ali , Nicolaou Savvas , Cibere Jolanda
Published: July 2020

Background

To evaluate whether knee osteoarthritis (OA) manifestations predict depression and anxiety using cross-sectional and longitudinal prediction models.

Methods

A population-based cohort (n = 122) with knee pain, aged 40–79, was evaluated at baseline, 3 and 7 years. Baseline predictors were: age decade; sex; BMI ≥ 25; physical exam knee effusion; crepitus; malalignment; quadriceps atrophy; flexion; flexion contracture; Kellgren-Lawrence (KL) x-ray grade (0/1/2/3+); WOMAC pain ≥25; WOMAC stiffness ≥25; self-reported knee swelling; and knee OA diagnosis (no/probable/definite). Depression and anxiety, cutoffs 5+ and 7+ respectively, were measured via the Hospital Anxiety and Depression Scale. We fit logistic models at each cycle using multivariable models selected via lowest Akaike’s information criterion.

Results

Baseline depression model: sex (female OR = 0.27; 0.10, 0.76) and KL grade (KL 1 OR = 4.21; 1.31, 13.48). Three-year depression model: KL grade (KL 1 OR = 18.92; 1.73, 206.25). Seven-year depression model: WOMAC stiffness ≥25 (OR = 3.49; 1.02, 11.94) and flexion contracture ≥1 degree (OR = 0.23; 0.07, 0.81). Baseline anxiety model: knee swelling (OR = 4.11; 1.51, 11.13) and age (50–59 vs. 40–49 OR = 0.31 [0.11, 0.85]; 60–69 OR = 0.07 [0.01, 0.42]). Three-year anxiety model: WOMAC stiffness ≥25 (OR = 5.80; 1.23, 27.29) and KL grade (KL 1 OR = 6.25; 1.04, 37.65). Seven-year anxiety model: sex (female OR = 2.71; 0.87, 8.46).

Conclusion

Specific knee OA-related manifestations predict depression and anxiety cross-sectionally, 3 years in the future, and for depression, 7 years in the future. This information may prove useful to clinicians in helping to identify patients most at risk of present or future depression and anxiety, thus facilitating preemptive discussions that may help counter that risk.
Implementation of minimally invasive gastrectomy for gastric cancer in a western tertiary referral center
Authors: Tsekrekos Andrianos , Triantafyllou Tania , Klevebro Fredrik , Hayami Masaru , Lindblad Mats , Nilsson Magnus , Lundell Lars , Rouvelas Ioannis
Published: July 2020

Background

Minimally invasive techniques have gradually come to take a leading position in the surgical treatment of gastrointestinal malignancies. In order to define an effective process for the implementation of similar techniques in the treatment of gastric cancer, patient caseload represents a pivotal factor for education and training, but is a prerequisite not fulfilled in most Western countries. Additionally, as opposed to the East, a variety of additional factors such as the usually advanced stage of the disease and differences in patient characteristics are prevailing and raise further obstacles. Hereby we report a strategy for a safe and effective process for the implementation of laparoscopic gastric cancer surgery in a Western tertiary referral center.

Methods

The present study describes the stepwise implementation of laparoscopic gastrectomy for the treatment of gastric cancer at a tertiary referral center, comprising the time period 2012–2019. This process was facilitated by a close collaboration with two high-volume centers in Japan, as well as exchanging fellowships and observerships between the Karolinska University Hospital and other European centers. From the initially strict selection of cases for laparoscopic surgery, laparoscopic gastrectomy has gradually become the preferred approach also in patients with locally advanced tumors.

Results

From January 1st 2010 until December 31st 2019, 249 patients were operated for gastric cancer, of whom 141 (56.6%) had an open and 108 (43.4%) a laparoscopic procedure. In the latter group, total gastrectomy was performed in 33.3% of the patients. While blood loss, operation time and length of stay decreased during the first years after implementation, these variables increased slightly during the last years of the study period, probably due to the higher proportion of advanced gastric cancer cases, as well as the higher rate of laparoscopic total gastrectomy with more extended lymphadenectomy.

Conclusions

Laparoscopic surgery is currently a valid therapeutic option for gastric cancer, which has expanded to also embrace total gastrectomy and locally advanced tumors. Collaboration between centers in the East and West, centralization to high-volume centers and application of enhanced recovery protocols are essential components in the implementation and further refinement of minimally invasive gastrectomy.
Using long-term ranging patterns to assess within-group and between-group competition in wild mountain gorillas
Authors: Seiler Nicole , Robbins Martha M.
Published: July 2020

Background

Competition within and between social groups determines access to resources and can be inferred from space use parameters that reflect depletion of food resources and competitive abilities of groups. Using location data from 1998 to 2017, we investigated within- and between-group competition in 12 groups of wild mountain gorillas (Gorilla beringei beringei). As within-group feeding competition is expected to increase with group size, an increase in group size is predicted to lead to an increase in the size of annual home ranges and core areas, but to a decrease in fidelity (reuse of an area). Due to asymmetries in competitive abilities, larger groups are expected to have higher exclusivity (degree of non-shared space) of annual home ranges and core areas than smaller groups.

Results

We found evidence of within-group feeding competition based on a positive relationship between group size and both annual home range and core area size as well as a negative relationship between group size and core area fidelity. Additionally, fidelity of core areas was lower than of home ranges. Between-group competition was inferred from a trend for groups with more members and more males to have more exclusive home ranges and core areas. Lastly, annual core areas were largely mutually exclusive.

Conclusions

Our study suggests that non-territorial, group-living animals can have highly dynamic, long-term avoidance-based spacing patterns, both temporally and spatially, to maintain annual core area exclusivity among groups while concurrently shifting these areas annually within overlapping home ranges to avoid resource depletion. Despite ranging in larger home ranges and core areas, larger groups were able to maintain more exclusive ranges than smaller groups, suggesting a competitive advantage for larger groups in between-group competition in a non-territorial species. Together, these findings contribute to understanding how social animals make behavioral adjustments to mitigate the effects of intraspecific competition.
ADAM15 expression is increased in lung CD8+ T cells, macrophages, and bronchial epithelial cells in patients with COPD and is inversely related to airflow obstruction
Authors: Wang Xiaoyun , Zhang Duo , Higham Andrew , Wolosianka Sophie , Gai Xiaoyan , Zhou Lu , Petersen Hans , Pinto-Plata Victor , Divo Miguel , Silverman Edwin K. , Celli Bartolome , Singh Dave , Sun Yongchang , Owen Caroline A.
Published: July 2020

Background

A disintegrin and metalloproteinase domain-15 (ADAM15) is expressed by activated leukocytes, and fibroblasts in vitro. Whether ADAM15 expression is increased in the lungs of COPD patients is not known.

Methods

ADAM15 gene expression and/or protein levels were measured in whole lung and bronchoalveolar lavage (BAL) macrophage samples obtained from COPD patients, smokers, and non-smokers. Soluble ADAM15 protein levels were measured in BAL fluid (BALF) and plasma samples from COPD patients and controls. Cells expressing ADAM15 in the lungs were identified using immunostaining. Staining for ADAM15 in different cells in the lungs was related to forced expiratory volume in 1 s (FEV1), ratio of FEV1 to forced vital capacity (FEV1/FVC), and pack-years of smoking history.

Results

ADAM15 gene expression and/or protein levels were increased in alveolar macrophages and whole lung samples from COPD patients versus smokers and non-smokers. Soluble ADAM15 protein levels were similar in BALF and plasma samples from COPD patients and controls. ADAM15 immunostaining was increased in macrophages, CD8+ T cells, epithelial cells, and airway α-smooth muscle (α-SMA)-positive cells in the lungs of COPD patients. ADAM15 immunostaining in macrophages, CD8+ T cells and bronchial (but not alveolar) epithelial cells was related inversely to FEV1 and FEV1/FVC, but not to pack-years of smoking history. ADAM15 staining levels in airway α-SMA-positive cells was directly related to FEV1/FVC. Over-expressing ADAM15 in THP-1 cells reduced their release of matrix metalloproteinases and CCL2.

Conclusions

These results link increased ADAM15 expression especially in lung leukocytes and bronchial epithelial cells to the pathogenesis of COPD.
Possible reversibility between epithelioid and sarcomatoid types of mesothelioma is independent of ERC/mesothelin expression
Authors: Kojima Masataka , Kajino Kazunori , Momose Shuji , Wali Nadila , Hlaing May Thinzar , Han Bo , Yue Liang , Abe Masaaki , Fujii Tomoaki , Ikeda Katsuhisa , Hino Okio
Published: July 2020

Background

Mesothelioma is histologically divided into three subgroups: epithelioid, sarcomatoid, and biphasic types. The epithelioid or sarcomatoid type is morphologically defined by polygonal or spindle-like forms of cells, respectively. The biphasic type consists of both components. It is not yet understood how histological differentiation of mesothelioma is regulated. ERC/mesothelin is expressed in most cases of the epithelioid type, but not in the sarcomatoid type of mesothelioma. Consequently, its expression is well correlated to the histological subtype. We hypothesized that ERC/mesothelin expression influences the histological differentiation of mesothelioma, and tested this hypothesis.

Methods

We performed studies using the overexpression or knockdown of ERC/mesothelin in mesothelioma cells to examine its effect on cellular morphology, growth kinetics, or migration/invasion activity, in vitro. We then transplanted ERC/mesothelin-overexpressing and control cells into the intraperitoneal space of mice. We examined the effect of ERC/mesothelin overexpression on mouse survival and tumor phenotype.

Results

In vitro cell culture manipulations of ERC/mesothelin expression did not affect cellular morphology or proliferation, although its overexpression enhanced cellular adhesion and the migration/invasion activity of mesothelioma cells. The survival rate of mice following intraperitoneal transplantation of ERC/mesothelin-overexpressing mesothelioma cells was significantly lower than that of mice with control cells. The histological evaluation of the tumors, however, did not show any morphological difference between two groups, and our hypothesis was not validated. Unexpectedly, both groups (ERC/mesothelin-overexpressing and control) of mesothelioma cells that were morphologically monophasic and spindle-like in vitro differentiated into a biphasic type consisting of polygonal and spindle-like components in the transplanted tumor, irrespective of ERC/mesothelin expression.

Conclusions

These results suggested that the histological transition of mesothelioma between epithelioid and sarcomatoid types may be reversible and regulated not by ERC/mesothelin, but by other unknown mechanisms.
Plasmodium falciparum histidine-rich protein 2 diversity in Ghana
Authors: Addai-Mensah Otchere , Dinko Bismarck , Noagbe Mark , Ameke Selassie Louis , Annani-Akollor Max Efui , Owiredu Eddie-Williams , Mensah Kofi , Tackie Richmond , Togbe Eliezer , Agyare-Kwabi Comfort , Gyasi Charles , Adu-Gyamfi Constance , Debrah Alexander Yaw
Published: July 2020

Background

In the absence of microscopy, Plasmodium falciparum histidine-rich proteins 2 (PfHRP2)-based rapid diagnostic tests (RDTs) are recommended for the diagnosis of falciparum malaria, particularly in endemic regions. However, genetic variability of the pfhrp2 gene threatens the usefulness of the test due to its impact on RDT sensitivity. This study aimed to investigate the diversity of pfhrp2 in malaria cases among children in Ghana.

Methods

A cross-sectional study was conducted at the Adidome Government Hospital in the Volta Region of Ghana. A total of 50 children with mean age of 6.6 ± 3.5 years and diagnosed falciparum malaria were included. Blood samples were collected for complete blood count, malaria parasite identification and counting using auto analyzer and microscopy, respectively. DNA was isolated from blood-spotted Whatman filters, amplified and sequenced. Nucleotide sequences were translated in silico to corresponding amino acids and the deduced amino acids sequences were analyzed for diversity using Mega X.

Results

The number of repeats and number of each repeat within PfHRP2 varied between isolates. Twelve rare PfHRP2 repeat types, two of which are previously unreported, were identified in this study. The HRP2 sequence obtained in this study shared high similarities with isolates from Kenya. Using Baker’s regression model, Group B was the highest occurring type (58.0%). Screening of all sequences for epitopes recognized by PfHRP2-specific monoclonal antibodies (mAbs), the predominant motif was AHHAADAHH, which is recognized by the C1-13 mAbs.

Conclusion

This study reports diversity of P. falciparum HRP2 in samples from Ghanaian children with symptomatic malaria. The findings of this study highlight the existence of extra amino acid repeat types which adds to the PfHRP2 antigenic variability.
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Authors: Guo Tiantian , Zhang Denghong , Zeng Yuzhe , Huang Timothy Y. , Xu Huaxi , Zhao Yingjun
Published: July 2020

Alzheimer’s disease (AD) is the most common neurodegenerative disorder seen in age-dependent dementia. There is currently no effective treatment for AD, which may be attributed in part to lack of a clear underlying mechanism. Studies within the last few decades provide growing evidence for a central role of amyloid β (Aβ) and tau, as well as glial contributions to various molecular and cellular pathways in AD pathogenesis. Herein, we review recent progress with respect to Aβ- and tau-associated mechanisms, and discuss glial dysfunction in AD with emphasis on neuronal and glial receptors that mediate Aβ-induced toxicity. We also discuss other critical factors that may affect AD pathogenesis, including genetics, aging, variables related to environment, lifestyle habits, and describe the potential role of apolipoprotein E (APOE), viral and bacterial infection, sleep, and microbiota. Although we have gained much towards understanding various aspects underlying this devastating neurodegenerative disorder, greater commitment towards research in molecular mechanism, diagnostics and treatment will be needed in future AD research.
Associations between adherence to MIND diet and severity, duration and frequency of migraine headaches among migraine patients
Authors: Askarpour Moein , yarizadeh Habib , Sheikhi Ali , Khorsha Faezeh , Mirzaei Khadijeh
Published: July 2020

Objectives

Migraine is a neurological disorder causing unbearable pain. Dietary approach is proposed as a preventive way of reducing the severity of migraine headaches. The present study aimed to examine the association between MIND diet and migraine headaches.

Results

We found that participants with higher score of MIND diet compared to those with lower score, were less likely to have severe headaches (OR = 0.64; 95% CI 0.45, 0.91;P = 0.01). Moreover, our results showed an inversed correlation between mind diet score and duration (β = − 0.14, 95% CI − 1.42, − 0.14,P = 0.04) and frequency of headaches (β = − 0.13, 95% CI − 0.99, − 0.07,P = 0.03).
Follow-up after radiological intervention in oncology: ECIO-ESOI evidence and consensus-based recommendations for clinical practice
Authors: Maas Monique , Beets-Tan Regina , Gaubert Jean-Yves , Gomez Munoz Fernando , Habert Paul , Klompenhouwer Lisa G. , Vilares Morgado Paulo , Schaefer Niklaus , Cornelis Francois H. , Solomon Stephen B. , van der Reijd Denise , Bilbao Jose Ignacio
Published: July 2020

Interventional radiology plays an important and increasing role in cancer treatment. Follow-up is important to be able to assess treatment success and detect locoregional and distant recurrence and recommendations for follow-up are needed. At ECIO 2018, a joint ECIO-ESOI session was organized to establish follow-up recommendations for oncologic intervention in liver, renal, and lung cancer. Treatments included thermal ablation, TACE, and TARE. In total five topics were evaluated: ablation in colorectal liver metastases (CRLM), TARE in CRLM, TACE and TARE in HCC, ablation in renal cancer, and ablation in lung cancer. Evaluated modalities were FDG-PET-CT, CT, MRI, and (contrast-enhanced) ultrasound. Prior to the session, five experts were selected and performed a systematic review and presented statements, which were voted on in a telephone conference prior to the meeting by all panelists. These statements were presented and discussed at the ECIO-ESOI session at ECIO 2018. This paper presents the recommendations that followed from these initiatives. Based on expert opinions and the available evidence, follow-up schedules were proposed for liver cancer, renal cancer, and lung cancer. FDG-PET-CT, CT, and MRI are the recommended modalities, but one should beware of false-positive signs of residual tumor or recurrence due to inflammation early after the intervention. There is a need for prospective preferably multicenter studies to validate new techniques and new response criteria. This paper presents recommendations that can be used in clinical practice to perform the follow-up of patients with liver, lung, and renal cancer who were treated with interventional locoregional therapies.
A glance on the role of actin in osteogenic and adipogenic differentiation of mesenchymal stem cells
Authors: Khan Asmat Ullah , Qu Rongmei , Fan Tingyu , Ouyang Jun , Dai Jingxing
Published: July 2020

Mesenchymal stem cells (MSCs) have the capacity to differentiate into multiple lineages including osteogenic and adipogenic lineages. An increasing number of studies have indicated that lineage commitment by MSCs is influenced by actin remodeling. Moreover, actin has roles in determining cell shape, nuclear shape, cell spreading, and cell stiffness, which eventually affect cell differentiation. Osteogenic differentiation is promoted in MSCs that exhibit a large spreading area, increased matrix stiffness, higher levels of actin polymerization, and higher density of stress fibers, whereas adipogenic differentiation is prevalent in MSCs with disrupted actin networks. In addition, the mechanical properties of F-actin empower cells to sense and transduce mechanical stimuli, which are also reported to influence differentiation. Various biomaterials, mechanical, and chemical interventions along with pathogen-induced actin alteration in the form of polymerization and depolymerization in MSC differentiation were studied recently. This review will cover the role of actin and its modifications through the use of different methods in inducing osteogenic and adipogenic differentiation.