bluuebunny/crossref_metadata_2025 huggingface dataset:
Scorpion alleviates bone cancer pain through inhibition of bone destruction and glia activation
Authors: Yu Jiachuan , Luo Yuanyuan , Jin Huidan , Lv Jiaxin , Zhou Tingting , Yabasin Iddrisu Baba , Wen Qingping
Published: February 2020

Background

Bone cancer pain is common in patients with advanced cancers as tumor metastasizes to bone. The inefficient clinical treatment severely reduces quality of life of bone cancer pain patients. During the pain status, activated spinal astrocytes and microglia release various inflammatory cytokines, resulting in spinal inflammation and the development of neuron sensitization. Scorpion is the dry body of Buthus martensii Karsch and is often used for various pain management in clinical practice. However, its function on bone cancer pain is unclear.

Methods

We investigated the effects of intragastric administration of scorpion on bone cancer pain induced by left tibial cavity injection of Walker 256 cells. Nociceptive behavior was measured using the von Frey filaments test and the spontaneous ambulatory pain score. The bone destruction was assessed by tibial radiographs. Expression of spinal cord astrocyte marker glial fibrillary acidic protein and microglial marker Iba1 was monitored by Western blot assay and immunofluorescence. Tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1β was detected by real-time polymerase chain reaction. The proliferation of Walker 256 cells was evaluated by CCK8 assay.

Results

Intragastric administration of scorpion reduced bone cancer pain behavior and relieved bone destruction, accompanied by decreased expression of spinal glial fibrillary acidic protein and Iba1 protein level and TNF-α, IL-6, and IL-1β mRNA level. Besides, scorpion inhibited proliferation of Walker 256 cells in a dose- and time-dependent manner.

Conclusion

Our results demonstrate that scorpion produces an analgesic effect in a rat model of bone cancer pain via inhibiting bone destruction and activation of spinal cord astrocytes and microglia.
Mystical and Other Alterations in Sense of Self: An Expanded Framework for Studying Nonordinary Experiences
Authors: Taves Ann
Published: February 2020

Although many researchers in psychology, religious studies, and psychiatry recognize that there is overlap in the experiences their subjects recount, disciplinary silos and challenges involved in comparing reported experiences have left us with little understanding of the mechanisms, whether biological, psychological, and/or sociocultural, through which these experiences are represented and differentiated. So-called mystical experiences, which some psychologists view as potentially sui generis, provide a test case for assessing whether we can develop an expanded framework for studying unusual experiences across disciplines and cultures. Evidence for the special nature of “mystical experience” rests on the operationalization of a metaphysically untestable construct in two widely used self-report scales: the Mysticism Scale and the Mystical Experiences Questionnaire. Consideration of the construct in light of research on alterations in sense of self induced by psychoactive drugs and meditation practices suggests that “positive experiences of undifferentiated unity” are not sui generis, but rather a type of “ego dissolution.” To better understand the nature and effects of unusual experiences, such as alterations in the sense of self, we need self-report measures that distinguish between generically worded experiences and the way they are appraised in terms of valence, significance, cause, and long-term effects in different contexts.
A ‘Distinctive’ Map of London: Women, Theatre and the Classics in 1893
Authors: Monrós-Gaspar Laura
Published: February 2020

Copious geographies of nineteenth-century London spectacle have been mapped following different scales and criteria. In this article, I invite readers to scrutinise London’s entertainment industry in 1893 focusing on the venues where modern reconfigurations and adaptations of Greek and Roman mythology by women were first staged. Such a map reveals microhistories of the streets, theatres, pleasure gardens and concert halls, where women as creators and agents of the classical revival played an essential role that has generally been forgotten by theatre historians and classical reception studies. As I aim to demonstrate, this new and gendered cartography challenges the notion of a classical repertoire and the boundaries between the popular and the legitimate.
The sexual health assessment
Authors: Davies Elin , Mulla Ebrahim
Published: February 2020

Primary care plays an important role in sexual healthcare, not least because of rising rates of sexually transmitted infections and a wide variation in local funding for sexual and reproductive healthcare. Sexual health assessment brings some unique challenges. Embarrassment and stigma can hinder assessment. In this article, we provide the basic structure of the sexual history, while reinforcing the skills needed for a sensitive, yet effective, consultation.
Expectancies, Values, and Costs of Innovating Identified by Canadian Innovators: A Motivational Basis for Supporting Innovation Talent Development
Authors: Soleas Eleftherios K.
Published: February 2020

Current studies in innovation are often siloed to specific disciplines, precluding a generalizable understanding useful to understanding the factors that promote and hinder individual motivation to innovate. This study integrates analysis of 30 interviews and 500 surveys of Canadian innovators from a variety of disciplines as a means of understanding the avenues that education could use to develop innovation talent. The results of this study point to the overstated role of rewards as drivers of developing innovation talent. These findings support the idea that programs that wish to support innovation for all learners should be guided by the primacy of decisions that build confidence and fulfill interest and perceived importance of the task at hand, as well as those mitigating the costs of innovating. The implementation of promotive and cost-mitigating strategies should be a high priority for educational efforts to stoke the development of innovation talent for learners in many contexts.
Implications of Anti-Inflammatory Nature of Exosomes in Knee Arthritis
Authors: Fang William , Vangsness C. Thomas
Published: February 2020

Exosomes are extracellular vesicles (EVs) released from cells that are a part of many biological and pathological processes, especially in intercellular communication. These vesicles are involved cell signaling, influence tissue and immune response, and serve as biomarkers for diseases. Most interesting are the exosomes that are released from mesenchymal stem cells (MSCs) for inflammation in joint diseases. Preliminary studies have demonstrated the advantages of using EVs rather than MSCs for cell free therapy. Research on exosomes have shown promising results as biomarkers for tracking the pathogenesis and prognosis of inflammatory arthritis. Therapeutically, animal studies have demonstrated immunosuppression, reversing inflammation, increasing chondrocyte proliferation, and drug delivery properties. The field of exosomes continues to develop and more basic science and clinical studies with safety and efficacy studies are needed.
Allogeneic hematopoietic stem-cell transplantation for myelofibrosis
Authors: Zhang Lining , Yang Fan , Feng Sizhou
Published: February 2020

Myelofibrosis is one of the Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms with heterogeneous clinical course. Though many treatment options, including Janus kinase (JAK) inhibitors, have provided clinical benefits and improved survival, allogeneic hematopoietic stem-cell transplantation (AHSCT) remains the only potentially curative therapy. Considering the significant transplant-related morbidity and mortality, it is crucial to decide who to proceed to AHSCT, and when. In this review, we discuss recent updates in patient selection, prior splenectomy, conditioning regimen, donor type, molecular mutation, and other factors affecting AHSCT outcomes. Relapse is a major cause of treatment failure; we also describe recent data on minimal residual disease monitoring and management of relapse. In addition, emerging studies have reported pretransplant therapy with ruxolitinib for myelofibrosis showing favorable results, and further research is needed to explore its use in the post-transplant setting.
Integrative East–West Medicine Intervention for Chronic Daily Headache: A Case Report and Care Perspective
Authors: Laube Justin G , Salles Araujo Thais , Taw Lawrence B
Published: February 2020

Chronic daily headache is a group of headache syndromes including most commonly chronic migraine and chronic tension-type headache, which often overlap, are complicated by medication overuse and are disabling, costly, and variable responsive to western pharmacotherapeutic interventions. There is growing research and awareness of integrative health approaches and therapies to address patients with chronic headache, yet limited examples of how to deliver this approach. This article reviews a commonly seen challenging case of a patient with overlapping chronic migraine and chronic tension-type headache complicated by medication overuse managed with an integrative east–west medicine intervention. This included person-centered biopsychosocial history taking, traditional Chinese medicine informed acupuncture, trigger point injections, and contributing factors modifications. A narrative review of the literature is presented to demonstrate an evidence-informed rationale for incorporating nonpharmacologic approaches to effectively help reduce the symptom burden of this patient population.
Point-of-Care Early Infant Diagnosis Improves Adherence to the Testing Algorithm in Kenya
Authors: Odhiambo Collins Otieno , Githuka George , Bowen Nancy , Kingwara Leonard , Onsase Jared , Ochuka Bernard , Waweru Michael , Masaba Rose , Matu Lucy , Mwangi Eliud , Cohn Jennifer
Published: February 2020

Introduction:

We determine the level of adherence to the revised Kenya early infant diagnosis (EID) algorithm during implementation of a point-of-care (POC) EID project.

Methods:

Data before (August 2016 to July 2017) and after (August 2017 to July 2018) introduction of POC EID were collected retrospectively from the national EID database and registers for 33 health facilities. We assessed the number of HIV-infected infants who underwent confirmatory testing and received baseline viral load test and proportion of infants with an initial negative result who had a subsequent test.

Results and Discussion:

Significantly higher number of infants accessed confirmatory testing (94.2% versus 38.6%; P < .0001) with POC EID. Baseline viral load test and follow-up testing at 6 months, although higher with POC EID, were not significantly different from the pre-POC EID intervention period.

Conclusion:

The POC EID implementation has the potential to increase proportion of infants who receive confirmatory testing, thus reducing the risk of false-positive results.
Emotion Regulation Therapy and Its Potential Role in the Treatment of Chronic Stress-Related Pathology Across Disorders
Authors: Renna Megan E. , Fresco David M. , Mennin Douglas S.
Published: February 2020

Although stress is an inevitable part of everyday life, its chronicity, severity, and perceived burden can result in enduring distress, which may manifest as heightened emotionality, contributing to a number of self-regulatory failures. Specifically, distress disorders are characterized, in part, by heightened sensitivity to underlying motivational systems related to threat/safety, reward/loss, or both. Further, individuals suffering from these conditions typically engage in perseverate negative thinking (e.g., worry, rumination, self-criticism) in an effort to manage motivationally relevant distress and often utilize these processes at the detriment of engaging in new contextual learning. Distress disorders are often brought on by enduring chronic stress, coupled with these maladaptive emotional, cognitive, and behavioral responses and ensuing impairment which contribute to and in turn worsen the deficits from these purported mechanisms. Emotion regulation therapy is a theoretically derived treatment that is based upon affective science to offer a blueprint for improving intervention by focusing on targeting the motivational responses and corresponding regulatory failures of individuals with distress disorders. Open and randomized controlled trials have demonstrated considerable preliminary evidence for the utility of emotion regulation therapy and its proposed mechanisms in treating the distress conditions.
What Makes a Process Theoretical Contribution?
Authors: Cloutier Charlotte , Langley Ann
Published: February 2020

In recent years, there have been many calls for scholars to innovate in their styles of conceptual work, and in particular to develop process theoretical contributions that consider the dynamic unfolding of phenomena over time. Yet, while there are templates for constructing conceptual contributions structured in the form variance theories, approaches to developing process models, especially in the absence of formal empirical data, have received less attention. To fill this gap, we build on a review of conceptual articles that develop process theoretical contributions published in two major journals ( Academy of Management Review and Organization Studies) to propose a typology of four process theorizing styles that we label linear, parallel, recursive and conjunctive. As we move from linear to parallel to recursive to conjunctive styles, conceptual reasoning becomes more deeply embedded in process ontology, while the standard structuring devices such as diagrams, tables and propositions traditionally employed in conceptual articles appear less useful. We offer recommendations that may be helpful in enriching and deepening process theoretical contributions of all types.
A validated novel continuous prognostic index to deliver stratified medicine in pediatric acute lymphoblastic leukemia
Authors: Enshaei Amir , O’Connor David , Bartram Jack , Hancock Jeremy , Harrison Christine J. , Hough Rachael , Samarasinghe Sujith , den Boer Monique L. , Boer Judith M. , de Groot-Kruseman Hester A. , Marquart Hanne V. , Noren-Nystrom Ulrika , Schmiegelow Kjeld , Schwab Claire , Horstmann Martin A. , Escherich Gabriele , Heyman Mats , Pieters Rob , Vora Ajay , Moppett John , Moorman Anthony V.
Published: February 2020

Risk stratification is essential for the delivery of optimal treatment in childhood acute lymphoblastic leukemia. However, current risk stratification algorithms dichotomize variables and apply risk factors independently, which may incorrectly assume identical associations across biologically heterogeneous subsets and reduce statistical power. Accordingly, we developed and validated a prognostic index (PIUKALL) that integrates multiple risk factors and uses continuous data. We created discovery (n = 2405) and validation (n = 2313) cohorts using data from 4 recent trials (UKALL2003, COALL-03, DCOG-ALL10, and NOPHO-ALL2008). Using the discovery cohort, multivariate Cox regression modeling defined a minimal model including white cell count at diagnosis, pretreatment cytogenetics, and end-of-induction minimal residual disease. Using this model, we defined PIUKALL as a continuous variable that assigns personalized risk scores. PIUKALL correlated with risk of relapse and was validated in an independent cohort. Using PIUKALL to risk stratify patients improved the concordance index for all end points compared with traditional algorithms. We used PIUKALL to define 4 clinically relevant risk groups that had differential relapse rates at 5 years and were similar between the 2 cohorts (discovery: low, 3% [95% confidence interval (CI), 2%-4%]; standard, 8% [95% CI, 6%-10%]; intermediate, 17% [95% CI, 14%-21%]; and high, 48% [95% CI, 36%-60%; validation: low, 4% [95% CI, 3%-6%]; standard, 9% [95% CI, 6%-12%]; intermediate, 17% [95% CI, 14%-21%]; and high, 35% [95% CI, 24%-48%]). Analysis of the area under the curve confirmed the PIUKALL groups were significantly better at predicting outcome than algorithms employed in each trial. PIUKALL provides an accurate method for predicting outcome and more flexible method for defining risk groups in future studies.
Targeting cytokine- and therapy-induced PIM1 activation in preclinical models of T-cell acute lymphoblastic leukemia and lymphoma
Authors: De Smedt Renate , Morscio Julie , Reunes Lindy , Roels Juliette , Bardelli Valentina , Lintermans Beatrice , Van Loocke Wouter , Almeida Afonso , Cheung Laurence C. , Kotecha Rishi S. , Mansour Marc R. , Uyttebroeck Anne , Vandenberghe Peter , La Starza Roberta , Mecucci Cristina , Lammens Tim , Van Roy Nadine , De Moerloose Barbara , Barata João T. , Taghon Tom , Goossens Steven , Van Vlierberghe Pieter
Published: February 2020

T-cell acute lymphoblastic leukemia (T-ALL) and T-cell acute lymphoblastic lymphoma (T-LBL) are aggressive hematological malignancies that are currently treated with high-dose chemotherapy. Over the last several years, the search toward novel and less-toxic therapeutic strategies for T-ALL/T-LBL patients has largely focused on the identification of cell-intrinsic properties of the tumor cell. However, non–cell-autonomous activation of specific oncogenic pathways might also offer opportunities that could be exploited at the therapeutic level. In line with this, we here show that endogenous interleukin 7 (IL7) can increase the expression of the oncogenic kinase proviral integration site for Moloney-murine leukemia 1 (PIM1) in CD127+ T-ALL/T-LBL, thereby rendering these tumor cells sensitive to in vivo PIM inhibition. In addition, using different CD127+ T-ALL/T-LBL xenograft models, we also reveal that residual tumor cells, which remain present after short-term in vivo chemotherapy, display consistent upregulation of PIM1 as compared with bulk nontreated tumor cells. Notably, this effect was transient as increased PIM1 levels were not observed in reestablished disease after abrogation of the initial chemotherapy. Furthermore, we uncover that this phenomenon is, at least in part, mediated by the ability of glucocorticoids to cause transcriptional upregulation of IL7RA in T-ALL/T-LBL patient-derived xenograft (PDX) cells, ultimately resulting in non–cell-autonomous PIM1 upregulation by endogenous IL7. Finally, we confirm in vivo that chemotherapy in combination with a pan-PIM inhibitor can improve leukemia survival in a PDX model of CD127+ T-ALL. Altogether, our work reveals that IL7 and glucocorticoids coordinately drive aberrant activation of PIM1 and suggests that IL7-responsive CD127+ T-ALL and T-LBL patients could benefit from PIM inhibition during induction chemotherapy.
Gut-brain Axis and migraine headache: a comprehensive review
Authors:   On behalf of the School of Advanced Studies of the European Headache Federation (EHF-SAS), Arzani Mahsa , Jahromi Soodeh Razeghi , Ghorbani Zeinab , Vahabizad Fahimeh , Martelletti Paolo , Ghaemi Amir , Sacco Simona , Togha Mansoureh
Published: February 2020

The terminology “gut-brain axis “points out a bidirectional relationship between the GI system and the central nervous system (CNS). To date, several researches have shown that migraine is associated with some gastrointestinal (GI) disorders such as Helicobacter pylori (HP) infection, irritable bowel syndrome (IBS), and celiac disease (CD). The present review article aims to discuss the direct and indirect evidence suggesting relationships between migraine and the gut-brain axis. However, the mechanisms explaining how the gut and the brain may interact in patients with migraine are not entirely clear. Studies suggest that this interaction seems to be influenced by multiple factors such as inflammatory mediators (IL-1β, IL-6, IL-8, and TNF-α), gut microbiota profile, neuropeptides and serotonin pathway, stress hormones and nutritional substances. Neuropeptides including CGRP, SP, VIP, NPY are thought to have antimicrobial impact on a variety of the gut bacterial strains and thus speculated to be involved in the bidirectional relationship between the gut and the brain. According to the current knowledge, migraine headache in patients harboring HP might be improved following the bacteria eradication. Migraineurs with long headache history and high headache frequency have a higher chance of being diagnosed with IBS. IBS and migraine share some similarities and can alter gut microflora composition and thereby may affect the gut-brain axis and inflammatory status. Migraine has been also associated with CD and the condition should be searched particularly in patients with migraine with occipital and parieto-occipital calcification at brain neuroimaging. In those patients, gluten-free diet can also be effective in reducing migraine frequency. It has also been proposed that migraine may be improved by dietary approaches with beneficial effects on gut microbiota and gut-brain axis including appropriate consumption of fiber per day, adhering to a low glycemic index diet, supplementation with vitamin D, omega-3 and probiotics as well as weight loss dietary plans for overweight and obese patients.
Correction to: Gel electrophoresis of human sperm: a simple method for evaluating sperm protein quality
Authors: Jumeau Fanny , Sigala Julien , Fernandez-Gomez Francisco-Jose , Eddarkaoui Sabiha , Duban-Deweer Sophie , Buée Luc , Béhal Hélène , Sergeant Nicolas , Mitchell Valérie
Published: February 2020

Following publication of the original article [1], the authors reported that the author given names and family names had been transposed. The author names in this correction article are presented correctly.
Genome-wide identification and analysis of B-BOX gene family in grapevine reveal its potential functions in berry development
Authors: Wei Hongru , Wang Peipei , Chen Jianqing , Li Changjun , Wang Yongzhang , Yuan Yongbing , Fang Jinggui , Leng Xiangpeng
Published: February 2020

Background

The B-BOX (BBX) proteins are the class of zinc-finger transcription factors and can regulate plant growth, development, and endure stress response. In plants, the BBX gene family has been identified in Arabidopsis, rice, and tomato. However, no systematic analysis of BBX genes has been undertaken in grapevine.

Results

In this study, 24 grapevine BBX (VvBBX) genes were identified by comprehensive bioinformatics analysis. Subsequently, the chromosomal localizations, gene structure, conserved domains, phylogenetic relationship, gene duplication, and cis-acting elements were analyzed. Phylogenetic analysis divided VvBBX genes into five subgroups. Numerous cis-acting elements related to plant development, hormone and/or stress responses were identified in the promoter of the VvBBX genes. The tissue-specific expressional dynamics of VvBBX genes demonstrated that VvBBXs might play important role in plant growth and development. The transcript analysis from transcriptome data and qRT-PCR inferred that 11 VvBBX genes were down-regulated in different fruit developmental stages, while three VvBBX genes were up-regulated. It is also speculated that VvBBX genes might be involved in multiple hormone signaling (ABA, ethylene, GA3, and CPPU) as transcriptional regulators to modulate berry development and ripening. VvBBX22 seems to be responsive to multiple hormone signaling, including ABA, ethylene GA3, and CPPU. Some VvBBX genes were strongly induced by Cu, salt, waterlogging, and drought stress treatment. Furthermore, the expression of VvBBX22 proposed its involvement in multiple functions, including leaf senescence, abiotic stress responses, fruit development, and hormone response.

Conclusions

Our results will provide the reference for functional studies of BBX gene family, and highlight its functions in grapevine berry development and ripening. The results will help us to better understand the complexity of the BBX gene family in abiotic stress tolerance and provide valuable information for future functional characterization of specific genes in grapevine.
Higher growth of the apple (Malus × domestica Borkh.) fruit cortex is supported by resource intensive metabolism during early development
Authors: Jing Shan , Malladi Anish
Published: February 2020

Background

The major fleshy tissues of the apple fruit are spatially separable into cortex and pith. These tissues display differential growth during development. Key features of such differential growth, and sink metabolic programs supporting it have not been investigated previously. We hypothesized that differential growth between these fruit tissues is supported by differential sink metabolic programs, particularly during early development. Growth, metabolite concentrations, and transcript abundance of metabolism-related genes were measured to determine characteristics of differential growth and their underlying metabolic programs.

Results

The cortex displayed > 5-fold higher growth than the pith during early fruit development, indicating that differential growth was established during this period. Further, when resource availability was increased through sink-removal, cortex growth was preferentially enhanced. Greatest diversity in metabolic programs between these tissues was evident during early fruit development. Higher cortex growth during early development was facilitated by increased catabolism of imported carbon (C) resources, sorbitol and sucrose, and the nitrogen (N) resource, asparagine. It was also associated with enhanced primary C metabolism, and C storage as malate and quinate. The pith metabolic program during this period involved limited allocation of C and N to growth, but greater allocation to storage, and enhanced sucrose-sucrose cycling.

Conclusions

Together, these data indicate that the fruit cortex tissue displays a resource intensive metabolic program during early fruit development. This provides the C backbones, proteins, energy and osmolytes to support its higher growth.
A PTPN11 mutation in a woman with Noonan syndrome and protein-losing enteropathy
Authors: Wang Na , Shi Wen , Jiao Yang
Published: February 2020

Background

Noonan syndrome is an autosomal dominant, variably expressed multisystem disorder characterized by specific facial and cardiac defects, delayed growth, ectodermal abnormalities, and lymphatic dysplasias. Lymphedema and chylous pleural effusions are common in Noonan syndrome, but protein-losing enteropathy (PLE) has only rarely been described in the condition and little is known about its genetic associations.

Case presentation

We report the case of a 30-year-old Chinese woman who developed severe recurrent edema and hypoproteinemia. Gastroduodenoscopy showed a “snowflake” appearance of lymphangiectasia in the duodenum, and CT reconstruction of the small intestine showed segmental thickening of the intestinal wall with localized stenosis. Whole exome sequencing revealed that the patient harbored a pathogenic variant of PTPN11 (c.A922G p.N308D), which was unfortunately inherited by her 2.5-year-old daughter who had short stature and atrial septal defect but no hypoproteinemia.

Conclusions

This case of Noonan syndrome with PLE was associated with a PTPN11 mutation. A comprehensive review of PLE in Noonan syndrome revealed that PLE often presents late in this context but there is no clear genotype-phenotype correlation. Genetic evaluation with next-generation sequencing can be useful for securing the diagnosis and planning early intervention and management.
Faecal calprotectin is the biomarker that best distinguishes remission from different degrees of endoscopic activity in Crohn’s disease
Authors: e Penna Francisco Guilherme Cancela , Rosa Rodrigo Macedo , da Cunha Pedro Ferrari Sales , de Souza Stella Cristina Silva , de Abreu Ferrari Maria de Lourdes
Published: February 2020

Background

Effective control of the inflammatory process in Crohn’s disease (CD) is reflected in intestinal mucosal healing. The performances of faecal calprotectin (fcal), clinical and serologic parameters in the inflammatory activity evaluation and their correlation to the simple endoscopic score (SES-CD) are the goals of this study.

Methods

Patients with CD referred for ileocolonoscopy were prospectively included and distributed according to the degree of endoscopic inflammatory activity into remission, mild activity, and moderate to severe activity groups. The different degrees of endoscopic activity were correlated with the following indexes: Crohn’s disease activity index (CDAI), fCal, serum C-reactive protein (CRP), and haemogram. The control group comprised individuals without known intestinal disease who were referred for colorectal cancer screening.

Results

Eighty colonoscopies were performed in patients with CD and 21 in the control group. The control group had a lower median fCal (59.7 mcg/g) than patients with CD (683 mcg/g, p < 0.001). A moderate Spearman correlation occurred between SES-CD and CRP (r = 0.525), fCal (r = 0.450), and CDAI (r = 0.407), while a weak correlation was found with the platelet count (r = 0.257). Only fCal distinguished patients in remission from those with mild activity (236.6 mcg/g × 654.9 mcg/g, p = 0.014) or moderate to severe activity (236.6 mcg/g × 1128 mcg/g, p < 0.001). An fCal cut-off of 155 mcg/g was sensitive (96%) and accurate (78%) for the diagnosis of endoscopic activity.

Conclusions

fCal provides greater diagnostic accuracy than the other activity markers for endoscopic activity of patients with CD, moderate correlation to SES-CD, and a capacity to discriminate patients in remission from those with mild or moderate to severe activity.
Safety and effectiveness of acellular pertussis vaccination during pregnancy: a systematic review
Authors: Vygen-Bonnet Sabine , Hellenbrand Wiebke , Garbe Edeltraut , von Kries Rüdiger , Bogdan Christian , Heininger Ulrich , Röbl-Mathieu Marianne , Harder Thomas
Published: February 2020

Background

Infants < 3 months of age are at highest risk for developing severe complications after pertussis. The majority of pregnant women has low concentrations of pertussis-specific antibodies and thus newborns are insufficiently protected by maternally transferred antibodies. Acellular pertussis vaccination during pregnancy was recently implemented in various countries. Here, we assessed the evidence for safety and effectiveness of pertussis vaccination during pregnancy.

Methods

We searched Medline, Embase, and ClinicalTrials.gov from January 1st 2010 to January 10th 2019. We assessed risk of bias (ROB) using the Cochrane ROB tool and ROBINS-I. We evaluated the quality of evidence using the GRADE approach.

Results

We identified 1273 articles and included 22 studies (14 for safety; 8 for effectiveness), comprising 1.4 million pregnant women in safety studies and 855,546 mother-infant-pairs in effectiveness studies. No significant differences between vaccinated and unvaccinated women and their infants were observed for safety outcomes with the exception of fever and chorioamnionitis. Compared to no vaccination, three studies showed a significantly increased relative risk for the presence of the ICD-9 code for chorioamnionitis in electronic patient data after pertussis vaccination. However, no study reported an increased risk for clinical sequelae of chorioamnionitis after vaccination during pregnancy, such as preterm birth or neonatal intensive care unit admission. Vaccine effectiveness against pertussis in infants of immunized mothers ranged from 69 to 91% for pertussis prevention, from 91 to 94% for prevention of hospitalization and was 95% for prevention of death due to pertussis. Risk of bias was serious to critical for safety outcomes and moderate to serious for effectiveness outcomes. GRADE evidence quality was moderate to very low, depending on outcome.

Conclusion

Although an increased risk for a diagnosis of fever and chorioamnionitis was detected in pregnant women after pertussis vaccination, there was no association with a higher frequency of clinically relevant sequelae. Vaccine effectiveness for prevention of infant pertussis, hospitalization and death is high. Pertussis vaccination during pregnancy has an overall positive benefit-risk ratio. In view of the overall quality of available evidence ongoing surveillance of chorioamnionitis and its potential sequelae is recommended when pertussis vaccination in pregnancy is implemented.

Trial registration

PROSPERO CRD42018087814, CRD42018090357.
Modern treatment of perineuriomas: a case-series and systematic review
Authors: Uerschels Anne-Kathrin , Krogias Christos , Junker Andreas , Sure Ulrich , Wrede Karsten H. , Gembruch Oliver
Published: February 2020

Background

Perineuriomas are rare benign peripheral nerve sheath tumours of perineurial cell origin and can be classified into intraneural and extraneural perineuriomas. They most commonly present a mononeuropathy of gradual onset and slow progression, resulting in progressive neurological deficits like hypoesthesia or motor weakness. Therapy is still variable. Aim of the study was to compare our surgical treatment and our follow-up regime including high-resolution nerve sonography with the current literature to evaluate best treatment of perineuriomas.

Methods

Retrospective analysis of our dataset “peripheral nerve lesion” to identify patients suffering from perineuriomas between 01.01.2012 until 31.12.2018. Surgical treatment and the follow-up examination of three patients were described. Additionally, a systematic review including PubMed, the Cochrane Collaboration Library, Scopus and Google Scholar was performed for literature published between January 1, 1990 and October 31, 2019 independently by 2 authors.

Results

In the first case, the left ulnar nerve was affected. In the second case, the left peroneal nerve and in the third case the right median nerve was affected. High-resolution nerve sonography was performed in each case. All patients underwent interfascicular neurolysis combined with a targeted fascicular biopsy under electrophysiological monitoring. Neurological deficits improved subsidized by rehabilitation. Surgical therapy and the neurological outcome were compared with literature. Systematic review revealed 22 articles, which met the inclusion criteria. Therefore, demographics, surgical treatment and neurological outcome of 77 patients were analysed.

Conclusions

Perineuriomas are rare benign nerve sheath tumours with a slow progression, sometimes difficult to diagnose. Decompression and neurolysis may improve neurological deficits. High resolution nerve sonography might serve as a helpful additional diagnostic tool in this process.
Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma
Authors: Cho Inju , Lee Hansang , Yoon Sang Eun , Ryu Kyung Ju , Ko Young Hyeh , Kim Won Seog , Kim Seok Jin
Published: February 2020

Background

The interaction of programmed death-1 protein (PD-1) and programmed death-1 ligand (PD-L1) produces immunosuppressive activity, protecting tumor cells from anti-tumor immunity and possibly releasing soluble PD-L1 (sPD-L1) from PD-L1 expressing tumor cells. Therefore, we measured serum levels of sPD-L1 in patients with primary central nervous system lymphoma (PCNSL) and explored its clinical implications.

Methods

Sixty-eight patients with newly diagnosed PCNSL had diffuse large B-cell lymphoma and were treated with high-dose methotrexate-containing chemotherapy. The measurement of sPD-L1 and cytokines was performed using serum samples archived at diagnosis, and the tissue expression of PD-L1 was also analyzed from archived paraffin-embedded tissue blocks. Disease relapse, progression-free survival (PFS), and overall survival (OS) were analyzed according to the extent of sPD-L1 in serum and PD-L1 in tissue.

Results

The median level of serum sPD-L1 (0.429 ng/mL) was higher than in healthy control patients (0.364 ng/mL). The occurrence of relapse was more frequent in the high sPD-L1 (78%) than the low sPD-L1 group (50%), though the groups did not have different clinical or pathological characteristics at diagnosis. As a result, the OS and PFS for the high sPD-L1 group were significantly lower than those in the low group. PD-L1-positive tumor cells were found in 35 patients (67%), and the extent of PD-L1-postive tumor cells was positively associated with serum sPD-L1 levels (r = 0.299, P = 0.031). Among the 34 cytokines analyzed, only the serum level of IL-7 correlated with the serum level of sPD-L1 (r = 0.521, P < 0.001).

Conclusions

Serum levels of sPD-L1 could reflect the expression of PD-L1 in PCNSL tumor cells and predict patient survival outcomes. Therefore, sPD-L1 in serum could be a feasible biomarker for determining a risk-adapted treatment strategy for PCNSL patients.

Trial registration

The study population was patients who were diagnosed with PCNSL between January 2009 and February 2017 and registered for our prospective cohort studies after providing written informed consent (ClinicalTrials.gov: NCT00822731 [date of registration - January 14, 2009] and NCT01877109 [date of registration - June 13, 2013]).
Do NICU developmental care improve cognitive and motor outcomes for preterm infants? A systematic review and meta-analysis
Authors: Soleimani Farin , Azari Nadia , Ghiasvand Hesam , Shahrokhi Amin , Rahmani Nahid , Fatollahierad Shiva
Published: February 2020

Background

The aim of this study was to review the effects of developmental care in neonatal intensive care unit (NICU) setting on mental and motor development of preterm infants.

Method

We searched PubMed, EMBASE, CINAHL, Scopus, Web of Science and Cochrane library until October 8th 2017, and included randomized controlled trials that assessed effects of developmental care in NICU on mental and motor development of preterm infants at 12 and 24 months of age, using the Bayley scale of infant development in this systematic review. In addition, data were pooled by random effects model and Standardized Mean Difference (SMD) with 95% confidence intervals (CI), calculated for meta-analysis.

Results

Twenty one studies were eligible to be included in this systematic review; however, only thirteen studies had data suitable for meta-analysis. According to statistical analysis, developmental care in NICU improved mental developmental index (MDI) (standardized mean difference [SMD] 0.55, 95% confidence interval [CI] 0.23–0.87;p < 0.05), and psychomotor developmental index (PDI) (SMD 0.33, [CI] 95% CI 0.08–0.57;p < 0.05) of BSID at 12 months of age and PDI at 24 months of age (SMD 0.15, 95% CI -0.02–0.32;p < 0.1) of preterm infants. However, the benefit was not detected at 24 months of age on MDI (SMD 0.15, 95% CI -0.05–0.35;p = 0.15).

Conclusion

Current evidence suggests that developmental care in only NICU setting could have significant effect on mental and motor development of preterm infants, especially at 12 months of age. However, because of clinical heterogeneity, more studies are needed to evaluate the effects of developmental NICU care in the development of preterm infants.
Co-infection with Campylobacter and rotavirus in less than 5 year old children with acute gastroenteritis in Nepal during 2017–2018
Authors: Bhattarai Vishnu , Sharma Saroj , Rijal Komal Raj , Banjara Megha Raj
Published: February 2020

Background

Diarrhoea, although easily curable, is a global cause of death for a half million children every year. Rotavirus andCampylobacterare the most common etiological agents of diarrhoea in children less than 5 years of age. However, in Nepal, these causative agents are not routinely examined for the diagnosis and treatment. The main objective of this study was to determineCampylobacterco-infection associated with rotavirus diarrhoea in children less than 5 years of age.

Methods

A cross-sectional study was conducted at Kanti Children’s Hospital (KCH), Kathmandu, Nepal from November 2017 to April 2018. A total of 303 stool specimens from children affected with diarrhoea were processed to detect rotavirus using a rapid rotavirus antigen detection test kit, andCampylobacterby microscopy, culture and biochemical tests. Antibiotic susceptibility tests ofCampylobacterisolates were performed according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines 2015.

Results

Of 303 samples, 91 (30.0%) were positive for co-infection with rotavirus andCampylobacter. Rotavirus mono-infection was detected in 61 (20.1%), andCampylobactermono-infection was detected in 81 (26.7%) samples. Patient’s age, month of infection, untreated water and frequent soil contact were the major risk factors for infections. Clinical features such as > 9 loose motions per day, fever, vomiting, mild to moderate dehydration, diarrhea persisting 6–9 days and presence of mucus in stool were significant (p < 0.05) clinical features, and were more severe in coinfection compared to mono-infections in multivariate analysis.

Conclusion

The study shows a high rate of rotavirus andCampylobactercoinfection in children with diarrhoea. Diagnosis based management of diarrhoeal cases can guide the specific treatment.
The relationship between dietary patterns and depression mediated by serum levels of Folate and vitamin B12
Authors: Khosravi Maryam , Sotoudeh Gity , Amini Maryam , Raisi Firoozeh , Mansoori Anahita , Hosseinzadeh Mahdieh
Published: February 2020

Background

Major depressive disorder is among main worldwide causes of disability. The low medication compliance rates in depressed patients as well as the high recurrence rate of the disease can bring up the nutrition-related factors as a potential preventive or treatment agent for depression. The aim of this study was to investigate the association between dietary patterns and depression via the intermediary role of the serum folate and vitamin B12, total homocysteine, tryptophan, and tryptophan/competing amino acids ratio.

Methods

This was an individually matched case-control study in which 110 patients with depression and 220 healthy individuals, who completed a semi-quantitative food frequency questionnaire were recruited. We selected the depressed patients from three districts in Tehran through non-probable convenience sampling from which healthy individuals were selected, as well. The samples selection and data collection were performed during October 2012 to June 2013. In addition, to measure the serum biomarkers 43 patients with depression and 43 healthy people were randomly selected from the study population. To diagnose depression the criteria of Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were utilized.

Results

The findings suggest that the healthy dietary pattern was significantly associated with a reduced odds of depression (OR: 0.75; 95% CI: 0.61–0.93) whereas the unhealthy dietary pattern increased it (OR: 1.382, CI: 1.116–1.71). The mediation analysis showed that the healthy dietary pattern was associated with a reduced risk of depression via increased serum levels of the folate and vitamin B12; however, the unhealthy dietary pattern was associated with increased risk of depression via decreased serum levels of folate and vitamin B12, based on tree adjusted logistic regression models.

Conclusion

Dietary patterns may be associated with depression by changing the serum levels of folate and vitamin B12. Further studies are required to confirm the mechanism.
CHCHD2 is a potential prognostic factor for NSCLC and is associated with HIF-1a expression
Authors: Yin Xin , Xia Jinghua , Sun Ying , Zhang Zhipei
Published: February 2020

Background

CHCHD2 was identified a novel cell migration-promoting gene, which could promote cell migration and altered cell adhesion when ectopically overexpressed in NIH3T3 fibroblasts, and it was identified as a protein necessary for OxPhos function as well. However, the clinic relevance of CHCHD2 expression in NSCLC remains unclear. Here we assumed that CHCHD2 expression would accompanies the expression of HIF-1α to response hypoxia in the occurrence of NSCLC.

Methods

In order to verify this hypothesis, correlations among the expression levels of CHCHD2 and HIF-1α were detected and analyzed in 209 pair cases of NSCLC. The expression and location of these molecules were assessed using Immunohistochemistry, immunohistofluorescence, qRT-PCR and western blotting. The differences and correlations of the expression of these two molecules with clinical pathological characteristics in NSCLC were statistically analyzed using Wilcoxon (W) text, Mann-Whitney U, Kruskal-Wallis H and cross-table tests. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of the expression of CHCHD2 and HIF-1α on the patients’ survival.

Results

Data showed that CHCHD2 and HIF-1α expression were higher in NSCLC than in normal tissues (all P = 0.000). CHCHD2 expression was significantly related with smoking, tumor size, differentiation degree, TNM Stage, lymph metastasis (all P<0.05). The HIF-1α expression was significantly associated with smoking, tumor category, differentiation degree, TNM Stage, Lymph metastasis (all P<0.05). There was a marked correlation of CHCHD2 and HIF-1α expression with histological type, differentiation and lymph metastasis of NSCLC (all P<0.05, rs>0.3). Immunohistofluorescence showed that there were co-localization phenomenon in cytoplasm and nucleus between CHCHD2 and HIF-1α expression. NSCLC patients with higher CHCHD2 and HIF-1α expression had a significantly worse prognosis than those with lower CHCHD2 and HIF-1α expression (all P = 0.0001; log-rank test). The multivariate analysis indicated that CHCHD2 expression was an independent prognostic factor in NSCLC (hazard ratio [HR], 0.492, P = 0.001).

Conclusion

Our results indicate that over-expression of CHCHD2 would promote the expression of HIF-1α to adapt the hypoxia microenviroment in NSCLC and CHCHD2 could serves as a prognostic biomarker in NSCLC.
Respiratory viruses in mechanically ventilated patients: a pilot study
Authors: Nazareth Raquel , Chasqueira Maria-Jesus , Rodrigues Maria-Lúcia , Paulino Carolina , Conceição Catarina , Lêdo Lia , Segura Úrsula , Santos Madalena , Messias António , Póvoa Pedro , Paixão Paulo
Published: February 2020

Background

Respiratory virome is an integral part of the human microbiome and its characterization may contribute to a better understanding of the changes that arise in the disease and, consequently, influence the approach and treatment of patients with acute lower respiratory infections.

The aim of this study was to evaluate the presence of respiratory viruses in the lower airways of individuals undergoing invasive mechanical ventilation, with and without acute lower respiratory infection (respectively WRI and WORI groups).

Methods

We studied 44 mini-bronchoalveolar lavage samples (collected with a double catheter, Combicath® kit) from patients with mean age in the seventh decade, 20 from WORI group and 24 from WRI group, who were hospitalized for acute respiratory failure in Intensive Care Units of two hospitals in the Lisbon area. Real-time PCR was applied to verify analyse the presence of 15 common respiratory viruses (adenovirus, human bocavirus, influenza virus A and B, repiratory syncytial virus, human parainfluenza virus types 1, 2, 3 and 4, human enterovirus, human rhinovirus, human metapneumovirus, human coronavirus group 1 (229E, NL63) and 2 (OC43, HKU1).

Results

Respiratory viruses were detected in six of the 20 patients in the WORI group: influenza AH3 (n = 2), parainfluenza virus 1/3 (n = 2), human rhinovirus (n = 2), respiratory syncytial virus (n = 1) and human metapneumovirus (n = 1).

In the WRI group, respiratory viruses were detected in 12 of the 24 patients: influenza AH3 (n = 3), human rhinovirus (n = 3), respiratory syncytial virus (n = 3), human metapneumovirus (n = 3), human bocavirus (n = 2) and human enterovirus (n = 1). Simultaneous detection of two viruses was recorded in two samples in both groups.

Conclusions

The results of this study suggest the presence of common respiratory viruses in the lower respiratory tract without causing symptomatic infection, even in carefully collected lower samples. This may have important implications on the interpretation of the results on the diagnostic setting.