bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prohibitin (PHB) expression is associated with aggressiveness in DLBCL and flavagline-mediated inhibition of cytoplasmic PHB functions induces anti-tumor effects
Authors: Bentayeb Hafidha , Aitamer Marine , Petit Barbara , Dubanet Lydie , Elderwish Sabria , Désaubry Laurent , de Gramont Armand , Raymond Eric , Olivrie Agnès , Abraham Julie , Jauberteau Marie-Odile , Troutaud Danielle 
Published: November 2019

Abstract

Background
Diffuse large B-cell lymphomas (DLBCLs) are aggressive lymphomas accounting for approximately a third of non-Hodgkin lymphomas. Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are scaffold proteins that promote mitochondria homeostasis and consequently cell survival, but biological functions of cytoplasmic PHBs remain largely unknown in DLBCL.

Methods
PHB expression was analyzed in 82 DLBCL biopsies and five DLBCL cell lines by immunohistochemistry (IHC) and Western blotting. Pharmacological inhibition of PHB using the synthetic flavagline FL3 was realized in vitro to gain insight PHB cellular functions. Effects of FL3 on DLBCL cell line viability, apoptosis, C-Raf-ERK–MNK–eIF4E signaling pathway and eIF4F complex formation and activity were evaluated by XTT assay, annexin V-FITC/PI dual staining and Western blotting respectively. Subcutaneous DLBCL xenograft model in SCID mice was also performed to determine in vivo FL3 effect.

Results
As in DLBCL cell lines, PHB1 and PHB2 were expressed in germinal center B-cell–like (GCB) and activated B-cell–like (ABC) subtypes. In patient samples, high PHB levels were associated with higher serum LDH (PHB1 and PHB2), IPIaa (PHB2), and Ki-67 (PHB2) expression. Higher PHB1 expression tends to be associated with shorter event-free survival (EFS) in patients, especially in male patients. FL3 induced apoptosis of DLBCL cell lines that was associated with inhibition of the ERK-MNK-eIF4E signaling pathway, including aggressive double/triple-hit DLBCL cell lines. This resulted in altered eIF4F complex formation and activity leading to a reduction of Bcl-2 and c-Myc expression levels. Moreover, FL3 strongly downregulated DLBCL cellular levels of Akt protein and AKT mRNA. FL3 antitumor activity was also confirmed in vivo in a murine xenograft model.

Conclusion
Our data indicate that PHB overexpression is associated with markers of tumor aggressiveness in DLBCL, and that targeting PHBs may be a therapeutic option, notably in aggressive subtypes.
SP600125 enhances C-2-induced cell death by the switch from autophagy to apoptosis in bladder cancer cells
Authors: Yu Haiyang , Wu Chun-Li , Wang Xiangyu , Ban Qianhong , Quan Chunhua , Liu Mengbo , Dong Hangqi , Li Jinfeng , Kim Gi-Young , Choi Yung Hyun , Wang Zhenya , Jin Cheng-Yun 
Published: November 2019

Abstract

Background
A natural compound Jaspine B and its derivative possess potential anti-cancer activities; However, little is known about the underlying mechanism. Here, the role of a new autophagy inducer Jaspine B derivative C-2 in suppressing bladder cancer cells was researched in vitro and in vivo.

Methods
The underlying mechanisms and anticancer effect of C-2 in bladder cancer cells were investigated by MTT, western blotting, immunoprecipitation and immunofluorescence assays. The key signaling components were investigated by using pharmacological inhibitors or specific siRNAs. In vivo, we designed a C-2 and SP600125 combination experiment to verify the effectiveness of compound.

Results
C-2 exhibits cytotoxic effect on bladder cancer cells, and JNK activated by C-2 triggers autophagy and up-regulates SQSTM1/p62 proteins, contributing to activation of Nrf2 pathway. Utilization of JNK inhibitor SP600125 or knockdown of JNK by siRNA potentiate the cytotoxicity of C-2 through down-regulation of p62 and LC3II proteins and up-regulation of active-Caspase3 proteins, enhance the cell death effect, facilitating the switch from autophagy to apoptosis. In vivo study, C-2 suppresses tumor growth in a xenograft mouse model of EJ cells without observed toxicity. Combined treatment with SP600125 further enhances tumor inhibition of C-2 associated with enhanced activation of caspase3 and reduction of autophagy.

Conclusions
It reveals a series of molecular mechanisms about SP600125 potentiate the cytotoxicity and tumor inhibition of C-2 in bladder cancer cells through promoting C-2-induced apoptosis, expecting it provides research basis and theoretical support for new drugs development.
The impact of the Sepsis-3 definition on ICU admission of patients with infection
Authors: Klimpel Jenny , Weidhase Lorenz , Bernhard Michael , Gries André , Petros Sirak 
Published: November 2019

Abstract

Background
Sepsis is defined as a life-threatening organ dysfunction due to a dysregulated inflammation following an infection. However, the impact of this definition on patient care is not fully clear. This study investigated the impact of the current definition on ICU admission of patients with infection.

Methods
We performed a prospective observational study over twelve months on consecutive patients presented to our emergency department and admitted for infection. We analyzed the predictive values of the quick sequential organ failure assessment (qSOFA) score, the SOFA score and blood lactate regarding ICU admission.

Results
We included 916 patients with the diagnosis of infection. Median age was 74 years (IQR 62–82 years), and 56.3% were males. There were 219 direct ICU admissions and 697 general ward admissions. A qSOFA score of ≥2 points had 52.9% sensitivity and 98.3% specificity regarding sepsis diagnosis. A qSOFA score of ≥2 points had 87.2% specificity but only 39.9% sensitivity to predict ICU admission. A SOFA score of ≥2 points had 97.4% sensitivity, but only 17.1% specificity to predict ICU admission, while a SOFA score of ≥4 points predicted ICU admission with 82.6% sensitivity and 71.7% specificity. The area under the receiver operating curve regarding ICU admission was 0.81 (95 CI, 0.77–0.86) for SOFA score, 0.55 (95% CI, 0.48–0.61) for blood lactate, and only 0.34 (95% CI, 0.28–0.40) for qSOFA on emergency department presentation.

Conclusions
While a positive qSOFA score had a high specificity regarding ICU admission, the low sensitivity of the score among septic patients as well as among ICU admissions considerably limited its value in routine patient management. The SOFA score was the better predictor of ICU admission, while the predictive value of blood lactate was equivocal.
Time to recovery and determinants of severe acute malnutrition among 6–59 months children treated at outpatient therapeutic programme in North Gondar zone, Northwest Ethiopia: a prospective follow up study
Authors: Mamo Worku Nigussu , Derso Terefe , Gelaye Kassahun Alemu , Akalu Temesgen Yihunie 
Published: November 2019

Abstract

Background
Despite the available interventions to tackle nutritional problems, there is scarce information on time to recovery and its determinants among children with SAM in Ethiopia.

Objective
This study was aimed at finding the time to recovery and determinants among 6–59 months children with severe acute malnutrition treated at an outpatient therapeutic programme in North Gondar zone, northwest Ethiopia.

Methods
Facility based prospective follow up study was conducted from March 24 to May 24, 2017. A total of 408 children with the age of 6–59 months were included in the study. Structured interviewer administered questionnaire was used. Anthropometric measurements were conducted every week. The median time of recovery, Kaplan Meier (KM) curve, and log rank test were computed. Both bi-variable and multivariable Cox regression model was fitted. To establish an association between time to recovery and its determinants 95% confidence interval (CI) and p-value < 0.05 were used. Proportional hazard assumption was checked graphically and using Schoenfeld residual test.

Results
Out of 389 children, 254 (65.3%) recovered. The median time to recovery was 38.5 ± IQR of 14 days. Children with diarrhoea AHR = 0.81 with 95% CI (0.73, 0.99), children taken amoxicillin AHR = 2.304 with 95% CI (1.68–3.161), and had vomiting at admission AHR = 0.430 with 95% CI (0.205, 0.904) were significant predictors of time to recovery.

Conclusions and recommendations
The overall time to recovery has not met the minimum sphere international standard which was lower than 75%. It is advisable to give emphasis to patients with diarrhoea and vomiting.
Whole-genome sequencing of ocular Chlamydia trachomatis isolates from Gadarif State, Sudan
Authors: Alkhidir Abdulazeem Abdulsalam Ibrahim , Holland Martin J. , Elhag Wafa Ibrahim , Williams Charlotte A. , Breuer Judith , Elemam Abdah Elfatih , El Hussain Khalid Mohamed Khalid , Ournasseir Mohammed Elfatih Hussein , Pickering Harry 
Published: November 2019

AbstractBackgroundTrachoma, caused by ocularChlamydia trachomatis, is the leading infectious cause of blindness worldwide. Sudan first reported trachoma in the 1930s and has since been consistently endemic. OcularC. trachomatispreviously isolated from trachoma patients in Sudan in 1963 was antigenically identical to an isolate from Saudi Arabia (A/SA1). No contemporary ocularC. trachomatiswhole genome sequences have been reported from Sudan.MethodsThis study sequenced twenty ocularC. trachomatisisolates to improve understanding of pathogen diversity in North-East Africa and examine for genomic variation specific to Sudan, possibly related to the persistence of trachoma in surveyed communities. High quality, whole genome sequences were obtained from 12/20 isolates.ResultsAll isolates were serovar A and hadtarPandtrpAsequences typical of classical, ocularC. trachomatisisolates. The Sudanese isolates formed a closely related subclade within the T2-trachoma clade ofC. trachomatisphylogeny distinct from geographically disparate ocular isolates, with little intra-population diversity. We found 333 SNPs that were conserved in Sudanese ocular isolates but rare compared to other ocularC. trachomatispopulations, which were focused in two genomic loci (CTA0172-CTA0173andCTA0482).ConclusionsLimited intra-population diversity and geographical clustering of ocularC. trachomatissuggests minimal transmission between and slow diversification within trachoma-endemic communities. However, diversity may have been higher pre-treatment in these communities. Over-representation of Sudan-specific SNPs in three genes suggests they may have an impact onC. trachomatisgrowth and transmission in this population.
Reanalysis of the physical and mental health summary scores of dialysis versus conservative care in older patients with advanced chronic kidney disease: a critical appraisal
Authors: Verberne Wouter R. , Dijkers Janneke , Kelder Johannes C. , Jellema Wilbert T. , van Delden Johannes J. M. , Bos Willem Jan W. 
Published: November 2019

AbstractObjectiveNon-dialytic conservative care is argued to be a reasonable treatment alternative for dialysis in selected older patients with advanced chronic kidney disease. We evaluated patient-relevant outcomes including health-related quality of life in a previous study. However, the scoring algorithm we used to calculate the physical and mental component summary scores of the Short Form-36 (SF-36) turned out to differ from comparable studies on this topic. The aim of this critical appraisal was to reanalyze the SF-36 summary scores in our patient cohort (≥ 70 years) using the more widely used scoring algorithm.ResultsPatients on conservative care (n = 23) had lower physical and mental component summary scores compared to patients not yet started on dialysis (n = 39), but similar compared to patients on dialysis (n = 34). These findings were similar to our original findings and did not change the conclusions. Several scoring algorithms are used for the SF-36 summary scores. Researchers should be aware of this fact and should use the same scoring algorithm across similar studies in a specific field to increase comparability. Using the more widely used scoring algorithm, the recalculated SF-36 summary scores of our patient cohort can now be compared to other studies.
A genome-wide DNA methylation signature for SETD1B-related syndrome
Authors: Krzyzewska I. M. , Maas S. M. , Henneman P. , Lip K. v. d. , Venema A. , Baranano K. , Chassevent A. , Aref-Eshghi E. , van Essen A. J. , Fukuda T. , Ikeda H. , Jacquemont M. , Kim H.-G. , Labalme A. , Lewis S. M. E. , Lesca G. , Madrigal I. , Mahida S. , Matsumoto N. , Rabionet R. , Rajcan-Separovic E. , Qiao Y. , Sadikovic B. , Saitsu H. , Sweetser D. A. , Alders M. , Mannens M. M. A. M. 
Published: November 2019

AbstractSETD1B is a component of a histone methyltransferase complex that specifically methylates Lys-4 of histone H3 (H3K4) and is responsible for the epigenetic control of chromatin structure and gene expression. De novo microdeletions encompassing this gene as well as de novo missense mutations were previously linked to syndromic intellectual disability (ID). Here, we identify a specific hypermethylation signature associated with loss of function mutations in theSETD1Bgene which may be used as an epigenetic marker supporting the diagnosis of syndromicSETD1B-related diseases. We demonstrate the clinical utility of this unique epi-signature by reclassifying previously identifiedSETD1BVUS (variant of uncertain significance) in two patients.
Physiologic expansion of human heart-derived cells enhances therapeutic repair of injured myocardium
Authors: Mount Seth , Kanda Pushpinder , Parent Sandrine , Khan Saad , Michie Connor , Davila Liliana , Chan Vincent , Davies Ross A. , Haddad Haissam , Courtman David , Stewart Duncan J. , Davis Darryl R. 
Published: November 2019

Abstract

Background
Serum-free xenogen-free defined media and continuous controlled physiological cell culture conditions have been developed for stem cell therapeutics, but the effect of these conditions on the relative potency of the cell product is unknown. As such, we conducted a head-to-head comparison of cell culture conditions on human heart explant-derived cells using established in vitro measures of cell potency and in vivo functional repair.

Methods
Heart explant-derived cells cultured from human atrial or ventricular biopsies within a serum-free xenogen-free media and a continuous physiological culture environment were compared to cells cultured under traditional (high serum) cell culture conditions in a standard clean room facility.

Results
Transitioning from traditional high serum cell culture conditions to serum-free xenogen-free conditions had no effect on cell culture yields but provided a smaller, more homogenous, cell product with only minor antigenic changes. Culture within continuous physiologic conditions markedly boosted cell proliferation while increasing the expression of stem cell-related antigens and ability of cells to stimulate angiogenesis. Intramyocardial injection of physiologic cultured cells into immunodeficient mice 1 week after coronary ligation translated into improved cardiac function and reduced scar burden which was attributable to increased production of pro-healing cytokines, extracellular vesicles, and microRNAs.

Conclusions
Continuous physiological cell culture increased cell growth, paracrine output, and treatment outcomes to provide the greatest functional benefit after experimental myocardial infarction.
Disruptive behaviors among nurses in Israel – association with listening, wellbeing and feeling as a victim: a cross-sectional study
Authors: Tikva Sigal Shafran , Kluger Avraham N. , Lerman Yulia 
Published: November 2019

AbstractObjectivesTo examine the association between listening and disruptive behaviors and the association between disruptive behavior and the wellbeing of the nurse. To test whether constructive and destructive listening has an incremental validity.MethodsA structured questionnaire survey that measured the (constructive & destructive) listening climate at work, exposure to disruptive behaviors, well-being and feeling as a victim. We presented this survey using the Qualtrics software.ResultsOf the final sample of 567 respondents who reported that they were nurses, MAge = 38.41, 67% indicated that they were exposed to some form of disruptive behavior. Experiencing listening in the ward was associated with low levels of exposure to disruptive behaviors; exposure to disruptive behaviors, in turn, predicted reduction in the nurses’ wellbeing; the reduction in wellbeing was especially pronounced among nurses who felt like a victim. Each of the facets of the listening measure—constructive listening and destructive listening—had incremental validity in predicting exposure to disruptive behaviors. Finally, the effect of exposure to disruptive behavior on wellbeing was curvilinear.ConclusionsDisruptive behavior is a major challenge to the workplace well-being for nurses. The victim mentality has an adverse impact on nurses. Preventive efforts aimed at reducing disruptive behaviors among nurses and decreasing their sense of victimization are crucial for the well-being of nurses.
Choice of therapeutic interventions and outcomes for the treatment of infections caused by multidrug-resistant gram-negative pathogens: a systematic review
Authors: Nørgaard Sarah Melissa , Jensen Camilla Skaarup , Aalestrup Josefine , Vandenbroucke-Grauls Christina M. J. E. , de Boer Mark G. J. , Pedersen Alma Becic 
Published: November 2019

Abstract

Background
Antimicrobial resistance is an increasingly serious threat to public health, and the increased occurrence of multidrug-resistant (MDR) bacteria is a concern in both high-income and low- and middle-income countries. The purpose of this systematic review was to identify and critically appraise current antimicrobial treatment options for infections with MDR Gram-negative bacteria.

Methods
A literature search for treatment of MDR extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, A. baumannii, and P. aeruginosa was conducted in MEDLINE in January 2019. Relevant studies published in English, German, and French that evaluated clinical success, microbiological success, and 30-day mortality outcomes were included. The population of interest was adult patients.

Results
Of 672 studies, 43 met the inclusion criteria. Carbapenems are the most common antibiotics used for the treatment of ESBL-producing Enterobacteriaceae. The clinical and microbiological success was similar for group 1 carbapenems (imipenem, meropenem, or doripenem), group 2 carbapenems (ertapenem), and non-carbapenem antibiotics. Mortality data were contradictory for group 1 carbapenems compared to group 2 carbapenems. The most common treatment option for A. baumannii and P. aeruginosa infections was intravenous colistin, regardless of infection site. Clinical success and mortality were similar in A. baumannii infections treated with colistin combination therapy vs. colistin monotherapy, whereas heterogeneous results were found with respect to microbiological success. Monotherapy and colistin combination therapy were used against P. aeruginosa with clinical and microbiological success (70–100%) depending on the infection site and severity, and the antibiotic used. Ceftazidime-avibactam therapy for ESBL-producing Enterobacteriaceae and P. aeruginosa showed good clinical success in one study.

Conclusion
We did not find robust evidence for antibiotic treatment of any infection with MDR Gram-negative bacteria, including ESBL-producing Enterobacteriaceae, A. baumannii, and P. aeruginosa, that would lead to a firm recommendation for one specific antibiotic over another or for monotherapy over combination therapy. The choice of antibiotic treatment should be based on susceptibility testing balancing the expected clinical success rate against the risk of development of antibiotic resistance and the risk of severe side effects.
Lower serum expression of miR-181c-5p is associated with increased plasma levels of amyloid-beta 1–40 and cerebral vulnerability in normal aging
Authors: Manzano-Crespo Marta , Atienza Mercedes , Cantero Jose L. 
Published: November 2019

Abstract

Background
Previous studies have shown that expression levels of miR-181c are downregulated by amyloid-β (Aβ) deposition and chronic cerebral hypoperfusion, both factors largely associated with the development of AD. Moreover, reduced 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET brain metabolism and volume loss of regions of the medial temporal lobe have been generally recognized as hallmarks of AD. Based on this evidence, we have here investigated potential associations between serum levels of miR-181c-5p and these AD signatures in asymptomatic elderly subjects.

Methods
Ninety-five normal elderly subjects underwent clinical, cognitive, structural MRI, and FDG-PET explorations. Serum expression levels of miR-181c-5p and plasma Aβ concentrations were further analyzed in this cohort. Regression analyses were performed to assess associations between serum miR-181c-5p levels and cognitive functioning, plasma Aβ, structural and metabolic brain changes.

Results
Decreased serum expression of miR-181c-5p was associated with increased plasma levels of Aβ1–40, deficits in cortical glucose metabolism, and volume reduction of the entorhinal cortex. No significant associations were found between lower miR-181c-5p levels and cognitive deficits or cortical thinning.

Conclusions
These findings suggest that deregulation of serum miR-181c-5p may indicate cerebral vulnerability in late life.
How alternative food networks work in a metropolitan area? An analysis of Solidarity Purchase Groups in Northern Italy
Authors: Baldi Lucia , Bertoni Danilo , Migliore Giuseppina , Peri Massimo 
Published: November 2019

AbstractOur paper focuses on Solidarity Purchase Group (SPG) participants located in a highly urbanized area, with the aim to investigate the main motivations underlining their participation in a SPG and provide a characterization of them. To this end, we carried out a survey of 795 participants involved in 125 SPGs in the metropolitan area of Milan (Italy). Taking advantage of a questionnaire with 39 questions, we run a factor analysis and a two-step cluster analysis to identify different profiles of SPG participants. Our results show that the system of values animating metropolitan SPG practitioners does not fully conform to that traditionally attributed to an alternative food network (AFN). In fact, considerations linked to food safety and healthiness prevail on altruistic motives such as environmental sustainability and solidarity toward small producers. Furthermore, metropolitan SPGs do not consider particularly desirable periurban and local food products. Observing the SPGs from this perspective, it emerges as such initiatives can flourish also in those places where the lack of connection with the surrounding territory is counterbalanced by the high motivation to buy products from trusted suppliers who are able to guarantee genuine and safe products, not necessarily located nearby.