bluuebunny/crossref_metadata_2025 huggingface dataset:
Chinese organic materialism and modern science studies: Rethinking Joseph Needham’s legacy
Authors: Bala Arun
Published: July 2020

Historian of science Joseph Needham argued in various papers and books that the philosophy of organic materialism that informed classical Chinese science not only nurtured Chinese discoveries in areas such as magnetic studies, but also obstructed the emergence of early modern mechanical science in China. Nevertheless, the emergence of field conceptions in late modern science led him to see that Chinese organic materialism could combine with mechanical conceptions to enrich late modern science. Although much attention has been paid to Needham’s historical and sociological views of Chinese science, there has been hardly any systematic focus on understanding his conception of the philosophy of Chinese science. This article explains why Chinese organic materialism not only nurtured Chinese science in the past, and hindered the emergence of modern science in China, but can also be part of a synthesis of late modern science transcending early Western science.
Improving the Reach of Clinical Practice Guidelines: An Experimental Investigation of Message Framing on User Engagement
Authors: Werntz Alexandra , Bufka Lynn , Adams Brian E. , Teachman Bethany A.
Published: July 2020

Despite strong evidence for the efficacy of treatments for posttraumatic stress disorder (PTSD), most affected individuals are not receiving these treatments, in part because they may not know that evidence-based treatments exist. The American Psychological Association published a website to disseminate information about its Clinical Practice Guideline for treating PTSD. In Study 1, Google Optimize was used in a field study to examine whether altering the subheadings to three of the website pages would increase site visitor engagement. On the main page and on the page with treatment descriptions, no subheading alterations improved engagement. On the Patients and Families page, the subheading “say goodbye to symptoms” improved engagement on three outcome variables, including clicking a link to find a psychologist (although there were a small number of clicks). In a preregistered conceptual replication in a sample not actively seeking information about the PTSD guideline ( N = 578), the results were not replicable. Results highlight challenges of disseminating information about evidence-based treatment.
Unpacking Everyday Critical Pedagogy: Languaging Critique and Dialogue
Authors: Taylor Laura A. , Hikida Michiko
Published: July 2020

This article explores how critical pedagogy unfolds in the everyday interactions between teachers and students. Specifically, Freirean constructs of critique and dialogue were explored in two key literacy events drawn from an ethnographically informed case study of one fourth-grade classroom. The events were first examined from an ethnographic perspective to understand how sociopolitical issue(s) were being critiqued (or avoided). These events were then analyzed again through microanalytic discourse analysis to explore how teachers and students jointly accomplished dialogue and critique through proposing and taking up of particular stances toward text(s). By juxtaposing these two analytic lenses, the researchers argue for an understanding of critical pedagogy, particularly the tenets of critique and dialogue, as interactionally co-constructed in the continually evolving, everyday talk between teachers and students. This article closes by considering the implications of this work for classroom-based literacy research that examines critical pedagogy.
Translation and annotation of the travel notes of a33mi21 Cave written by He Xiudong Dongba
Authors: Gan Lu
Published: July 2020

a33mi21 Cave 阿明洞 as the holy land of the Dongba religion is located in Baidi 白地, Sanba 三坝, Shangri-la, Yunnan province. Li Lincan, a grandmaster in the study of Dongba characters and the deputy director of the Taipei Palace Museum, paid homage to the a33mi21 Cave in 1942 and wrote an inscription. In 2005, his son Li Zaizhong, following in his father’s footsteps, paid a formal visit there again, and He Xiudong Dongba from Tacheng 塔城, traveling with him, recorded the pilgrimage journey in Dongba characters and translated it into Chinese, which is the first travelogue published in the Naxi language and has considerable research value. This paper has a verbatim translation and annotation of the travelogue and conducts preliminary research from the perspectives of the author and the age, the paper and the line, the frequency and number of words and text structure, the word relationships, the variants and transformation of the words, lexical features, and so forth.
Inflammation-driven activation of JAK/STAT signaling reversibly accelerates acute myeloid leukemia in vitro
Authors: Habbel Jan , Arnold Lucas , Chen Yiyang , Möllmann Michael , Bruderek Kirsten , Brandau Sven , Dührsen Ulrich , Hanoun Maher
Published: July 2020

Acute myeloid leukemia (AML) is characterized by a high relapse rate and dismal long-term overall survival which is related to persistence of leukemia-initiating cells in their niche. Different animal models of myeloid malignancies reveal how neoplastic cells alter the structural and functional characteristics of the hematopoietic stem cell niche to reinforce malignancy. Understanding and disruption of the microenvironmental interactions with AML cells are a vital need. Malignant niches frequently go along with inflammatory responses, but their impact on cancerogenesis often remains unexplored. Here, we uncovered an aberrant production of inflammatory cytokines in untreated AML bone marrow that was proved to promote the proliferation of leukemia cells. This inflammatory response induced an activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in AML blasts as well as bone marrow stromal cells that also fostered leukemia proliferation. Inhibition of JAK/STAT signaling using the selective JAK1/2 inhibitor ruxolitinib resulted in significant antileukemic activity in AML in vitro which is mediated through both cell-autonomous and microenvironment-mediated mechanisms. However, in a xenograft transplantation model, monotherapy with ruxolitinib did not achieve substantial antileukemic activity, possibly suggesting a complementary function of JAK1/2 inhibition in AML.
Platelet-derived extracellular vesicles infiltrate and modify the bone marrow during inflammation
Authors: French Shauna L. , Butov Kirill R. , Allaeys Isabelle , Canas Jorge , Morad Golnaz , Davenport Patricia , Laroche Audrée , Trubina Natalia M. , Italiano Joseph E. , Moses Marsha A. , Sola-Visner Martha , Boilard Eric , Panteleev Mikhail A. , Machlus Kellie R.
Published: July 2020

During inflammation, steady-state hematopoiesis switches to emergency hematopoiesis to repopulate myeloid cells, with a bias toward the megakaryocytic lineage. Soluble inflammatory cues are thought to be largely responsible for these alterations. However, how these plasma factors rapidly alter the bone marrow (BM) is not understood. Inflammation also drives platelet activation, causing the release of platelet-derived extracellular vesicles (PEVs), which package diverse cargo and reprogram target cells. We hypothesized that PEVs infiltrate the BM, providing a direct mode of communication between the plasma and BM environments. We transfused fluorescent, wild-type (MPL+) platelets into recipient cMpl−/−mice before triggering systemic inflammation. Twenty hours postinfusion, we observed significant infiltration of donor platelet-derived particles in the BM, which we tracked immunophenotypically (MPL+ immunohistochemistry staining) and quantified by flow cytometry. To determine if this phenomenon relates to humans, we extensively characterized both megakaryocyte-derived and PEVs generated in vitro and in vivo, and found enrichment of extracellular vesicles in bone marrow compared with autologous peripheral blood. Last, BM from cMpl−/− mice was cultured in the presence or absence of wild-type (MPL+) PEVs. After 72 hours, flow cytometry revealed increased megakaryocytes only in cultures with added PEVs. The majority of CD41+ cells were bound to PEVs, suggesting a PEV-mediated rescue of megakaryopoiesis. In conclusion, we report for the first time that plasma-residing PEVs infiltrate the BM. Further, PEVs interact with BM cells in vivo and in vitro, causing functional reprogramming that may represent a novel model of inflammation-induced hematopoiesis.
Late molecular recurrences in patients with chronic myeloid leukemia experiencing treatment-free remission
Authors: Rousselot Philippe , Loiseau Clémence , Delord Marc , Cayuela Jean Michel , Spentchian Marc
Published: July 2020

Treatment-free remission (TFR) is an opportunity for patients with chronic myeloid leukemia (CML). Reported cumulative incidence curves of molecular recurrence (MRec) arbor a 2-phase shape with mainly early events, but also some late events (late MRec [LMRec]). Having discontinued our first patient in 2004, we have access to a prolonged follow-up, enabling us to characterize these late events. Over 15 years, 128 patients from our institution were registered in the Stop Imatinib (STIM; A Study for Tyrosine Kinase Inhibitors Discontinuation [A-STIM]) trial. MRec was defined by the loss of major molecular response (BCR-ABL1IS >0.1%). At the first TFR attempt, patients had been taking a tyrosine kinase inhibitor for a median of 7.1 years and in BCR-ABL1IS ≤0.01% (MR4) for a median of 4 years. The median follow-up of patients in TFR was 6.5 years. The TFR rate was estimated to be 45.6% after 7 years. For 9/65 (14%) patients experiencing MRec, recurrence occurred after 2 years in TFR (median, 3.6 years). The residual rate of MRec after 2 years was estimated to be 18%. The probability of remaining in TFR was 65.4% for patients having experienced fluctuations of their minimal residual disease (MRD) (at least 2 consecutive measurements BCR-ABL1IS >0.0032% or loss of MR4), whereas it was 100% for those with stable MRD (P = .003). After 2 years in TFR, we observed an 18% residual rate of LMRec. These late events represent 14% of all MRec and occur in patients with fluctuating MRD measurements. A long-term molecular follow-up therefore remains mandatory for CML patients in TFR. The A-STIM study was registered at www.clinicaltrials.gov as #NCT02897245.
SABRTooth: a randomised controlled feasibility study of stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I nonsmall cell lung cancer considered to be at higher risk of complications from surgical resection
Authors: Franks Kevin N. , McParland Lucy , Webster Joanne , Baldwin David R. , Sebag-Montefiore David , Evison Matthew , Booton Richard , Faivre-Finn Corinne , Naidu Babu , Ferguson Jonathan , Peedell Clive , Callister Matthew E.J. , Kennedy Martyn , Hewison Jenny , Bestall Janine , Gregory Walter M. , Hall Peter , Collinson Fiona , Olivier Catherine , Naylor Rachel , Bell Sue , Allen Peter , Sloss Andrew , Snee Michael
Published: July 2020

Objectives

Stereotactic ablative radiotherapy (SABR) is a well-established treatment for medically inoperable peripheral stage I nonsmall cell lung cancer (NSCLC). Previous nonrandomised evidence supports SABR as an alternative to surgery, but high-quality randomised controlled trial (RCT) evidence is lacking. The SABRTooth study aimed to establish whether a UK phase III RCT was feasible.

Design and methods

SABRTooth was a UK multicentre randomised controlled feasibility study targeting patients with peripheral stage I NSCLC considered to be at higher risk of surgical complications. 54 patients were planned to be randomised 1:1 to SABR or surgery. The primary outcome was monthly average recruitment rates.

Results

Between July 2015 and January 2017, 318 patients were considered for the study and 205 (64.5%) were deemed ineligible. Out of 106 (33.3%) assessed as eligible, 24 (22.6%) patients were randomised to SABR (n=14) or surgery (n=10). A key theme for nonparticipation was treatment preference, with 43 (41%) preferring nonsurgical treatment and 19 (18%) preferring surgery. The average monthly recruitment rate was 1.7 patients against a target of three. 15 patients underwent their allocated treatment: SABR n=12, surgery n=3.

Conclusions

We conclude that a phase III RCT randomising higher risk patients between SABR and surgery is not feasible in the National Health Service. Patients have pre-existing treatment preferences, which was a barrier to recruitment. A significant proportion of patients randomised to the surgical group declined and chose SABR. SABR remains an alternative to surgery and novel study approaches are needed to define which patients benefit from a nonsurgical approach.
Cyclophilin inhibitors restrict Middle East respiratory syndrome coronavirusviainterferon-λin vitroand in mice
Authors: Sauerhering Lucie , Kupke Alexandra , Meier Lars , Dietzel Erik , Hoppe Judith , Gruber Achim D. , Gattenloehner Stefan , Witte Biruta , Fink Ludger , Hofmann Nina , Zimmermann Tobias , Goesmann Alexander , Nist Andrea , Stiewe Thorsten , Becker Stephan , Herold Susanne , Peteranderl Christin
Published: July 2020

While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV), cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use.

We elucidated the molecular mechanisms by which the cyclophilin inhibitors cyclosporin A (CsA) and alisporivir (ALV) restrict MERS-CoV to validate their suitability as readily available therapy in MERS-CoV infection.

Calu-3 cells and primary human alveolar epithelial cells (hAECs) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including calcineurin, nuclear factor of activated T-cells (NFATs) or mitogen-activated protein kinases. Novel CsA-induced pathways were identified by RNA sequencing and manipulated by gene knockdown or neutralising antibodies. Viral replication was quantified by quantitative real-time PCR and 50% tissue culture infective dose. Data were validated in a murine MERS-CoV infection model.

Both CsA and ALV reduced MERS-CoV titres and viral RNA replication in Calu-3 cells and hAECs, improving epithelial integrity. While neither calcineurin nor NFAT inhibition reduced MERS-CoV propagation, blockade of c-Jun N-terminal kinase diminished infectious viral particle release but not RNA accumulation. Importantly, CsA induced interferon regulatory factor 1 (IRF1), a pronounced type III interferon (IFNλ) response and expression of antiviral genes. Downregulation of IRF1 or IFNλ increased MERS-CoV propagation in the presence of CsA. Importantly, oral application of CsA reduced MERS-CoV replicationin vivo, correlating with elevated lung IFNλ levels and improved outcome.

We provide evidence that cyclophilin inhibitors efficiently decrease MERS-CoV replicationin vitroandin vivo viaupregulation of inflammatory antiviral cell responses, in particular IFNλ. CsA might therefore represent a promising candidate for treating MERS-CoV infection.
Vitamin C to pregnant smokers persistently improves infant airway function to 12 months of age: a randomised trial
Authors: McEvoy Cindy T. , Shorey-Kendrick Lyndsey E. , Milner Kristin , Schilling Diane , Tiller Christina , Vuylsteke Brittany , Scherman Ashley , Jackson Keith , Haas David M. , Harris Julia , Park Byung S. , Vu Annette , Kraemer Dale F. , Gonzales David , Bunten Carol , Spindel Eliot R. , Morris Cynthia D. , Tepper Robert S.
Published: July 2020

Background

Vitamin C (500 mg·day−1) supplementation for pregnant smokers has been reported to increase newborn pulmonary function and infant forced expiratory flows (FEFs) at 3 months of age. Its effect on airway function through 12 months of age has not been reported.

Objective

To assess whether vitamin C supplementation to pregnant smokers is associated with a sustained increased airway function in their infants through 12 months of age.

Methods

This is a pre-specified secondary outcome of a randomised, double-blind, placebo-controlled trial that randomised 251 pregnant smokers between 13 and 23 weeks of gestation: 125 to 500 mg·day−1vitamin C and 126 to placebo. Smoking cessation counselling was provided. FEFs performed at 3 and 12 months of age were analysed by repeated-measures analysis of covariance.

Results

FEFs were performed in 222 infants at 3 months and 202 infants at 12 months of age. The infants allocated to vitamin C had significantly increased FEFs over the first year of life compared to those allocated to placebo. The overall increased flows were 40.2 mL·s−1for at FEF75(75% of forced vital capacity (FVC)) (adjusted 95% CI for difference 6.6–73.8; p=0.025); 58.3 mL·s−1for FEF50(10.9–105.8; p=0.0081); and 55.1 mL·s−1for FEF25–75(9.7–100.5; p=0.013).

Conclusions

In offspring of pregnant smokers randomised to vitamin Cversusplacebo, vitamin C during pregnancy was associated with a small but significantly increased airway function at 3 and 12 months of age, suggesting a potential shift to a higher airway function trajectory curve. Continued follow-up is underway.
P2X7 receptors exert a permissive effect on the activation of presynaptic AMPA receptors in rat trigeminal caudal nucleus glutamatergic nerve terminals
Authors: Currò Diego , Navarra Pierluigi , Samengo Irene , Martire Maria
Published: July 2020

Background

Purine receptors play roles in peripheral and central sensitization and are associated with migraine headache. We investigated the possibility that ATP plays a permissive role in the activation of AMPA receptors thus inducing Glu release from nerve terminals isolated from the rat trigeminal caudal nucleus (TCN).

Methods

Nerve endings isolated from the rat TCN were loaded with [3H]D-aspartic acid ([3H]D-ASP), layered into thermostated superfusion chambers, and perfused continuously with physiological medium, alone or with various test drugs. Radioactivity was measured to assess [3H]D-ASP release under different experimental conditions.

Results

Synaptosomal [3H]D-ASP spontaneous release was stimulated by ATP and to an even greater extent by the ATP analogue benzoylbenzoylATP (BzATP). The stimulation of [3H]D-ASP basal release by the purinergic agonists was prevented by the selective P2X7 receptor antagonist A438079. AMPA had no effect on basal [3H]D-ASP release, but the release observed when synaptosomes were exposed to AMPA plus a purinoceptor agonist exceeded that observed with ATP or BzATP alone. The selective AMPA receptor antagonist NBQX blocked this “excess” release. Co-exposure to AMPA and BzATP, each at a concentration with no release-stimulating effects, evoked a significant increase in [3H]D-ASP basal release, which was prevented by exposure to a selective AMPA antagonist.

Conclusions

P2X7 receptors expressed on glutamatergic nerve terminals in the rat TCN can mediate Glu release directly and indirectly by facilitating the activation of presynaptic AMPA receptors. The high level of glial ATP that occurs during chronic pain states can promote widespread release of Glu as well as can increase the function of AMPA receptors. In this manner, ATP contributes to the AMPA receptor activation involved in the onset and maintenance of the central sensitization associated with chronic pain.
A Chronicle on Genetics and the March of Darwinian and Mendelian Medicine
Authors: Govindaraju Diddahally R.
Published: July 2020

Ken Burns, a well-known documentarian has produced a film titled, “The Gene: An Intimate History” based on Siddhartha Mukherjee’s book by the same name. The film focuses sharply on the history of genetics, the science of inheritance and variation, in particular, the gene, the central player in genetics, its discovery, structure and function as well as its myriad influence on development, growth, health, disease and evolution of all organisms. Importantly, he has shown how geneticists, physicians, patients and their families as well as society at large must cooperate, develop mutual trust and share ethical responsibilities in order to predict, prevent, manage and cure many inherited disorders. Mr. Burns has reinforced these ideas beautifully with illustrations, archived film footage, location filming and commentaries. The film also hints at the need for taking a unified Darwinian-Mendelian and Hippocratic approach toward building a healthier human society. In short, this is a beautiful and engrossing documentary on the future of Genetic Medicine.
Correction to: Comparison of the effects of adjuvant concurrent chemoradiotherapy and chemotherapy for resected biliary tract cancer
Authors: Kim Hyera , Heo Mi Hwa , Kim Jin Young
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
Tuberculin skin test conversion in patients under treatment with anti-tumor necrotizing factor alpha agents
Authors: Hejazi Mohammad-Esmaeil , Ahmadzadeh Atefeh , Khabbazi Alireza , Ebrahimi Aliasghar , Farmani Maryam , Hejazi Yasin
Published: July 2020

Background

Despite successful clinical outcomes of biologic medications in patients with chronic rheumatic diseases, some considerable adverse effects such as infections remain a major concern. Possibility of tuberculosis (TB) reactivation over treatment with anti-tumor necrotizing factor (TNF) alpha agents has necessitated a screening test before initiation of treatment. However, screening over the course of treatment is not recommended in those patients with negative baseline screening tests. This study aimed to evaluate the efficacy of tuberculin skin test (TST) before treatment in patients with chronic rheumatologic diseases who were indicated to receive anti-TNF-alpha therapy and the necessity of repeating this test over the course of treatment.

Methods

In this prospective study, patients with chronic rheumatologic diseases receiving anti-TNF-alpha agents were studied in a two-year period. TST was performed before treatment and those with positive results were excluded from the study. Thereafter, treatment with anti-TNF-alpha agents was initiated with the indicated dose. TST was repeated before administration of biologic treatment until TST became positive or 16 weeks after the initiation of treatment with anti-TNF-alpha.

Results

A total of 51 cases were studied, of whom one patient (1.9%) was excluded due to positive TST before treatment. All participants received infliximab and the TST test became positive in one patient (2%) 2 weeks after receiving the first dose. Also, the results of further tests at weeks 6, 10, and 14 were all negative for the remaining patients.

Conclusion

Due to the possibility of TST conversion after administration of anti-TNF-alpha therapy, it is important to consider TB monitoring in patients under treatment with these agents using available methods such as TST.
The impact on quality of life from informing diagnosis in patients with cancer: a systematic review and meta-analysis
Authors: Wan Miao , Luo Xianggui , Wang Juan , Mvogo Ndzana Louis. B , Chang Chen , Li Zhenfen , Zhang Jianglin
Published: July 2020

Background

The aim of this study was to assess the impact on quality of life from informing patients with cancer of their diagnosis and disease status.

Method

We searched the follow databases, PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), PsycINFO, WEB OF SCIENCE, Embase, CBM (Chinese Biomedical Literature database), WANFANG database (Chinese Medicine Premier), and CNKI (China National Knowledge Infrastructure), using the following terms: neoplasm, cancer, tumor, tumor, carcinoma, disclosure, truth telling, breaking bad news, knowledge, knowing, awareness, quality of life, QOL. Pairs of reviewers independently screened documents and extracted the data, and the meta-analysis was performed using Revman 5.0 software.

Results

Eleven thousand seven hundred forty records retrieved from the databases and 23 studies were included in the final analysis. A meta-analysis revealed that there were no differences in either the general quality of life and symptoms of fatigue, pain, dyspnea, insomnia, appetite loss, and diarrhea, between informed and uniformed cancer patients (P > 0.05). There were also no differences found between the patient groups in physical function, role function, cognitive activity, and emotional function (P > 0.05). In terms of vitality, patients who were completely informed about their diagnosis showed higher vitality than uniformed patients. Uninformed patients seemed to have lower social function scores. Between partly informed and uninformed cancer patients, no differences were found in their general quality of life, function domains, and disease-related symptoms (P > 0.05).

Conclusion

Informing cancer patients of their diagnosis may not have a detrimental effect on their quality of life.

Trial registration

CRD42017060073.
“Bariatric families”- a new phenomenon with unique characteristics
Authors: Weiss Netta , Kalamitzky Nataly , Interator Hagar , Lubetzky Ronit , Moran-Lev Hadar
Published: July 2020

Background

Many obese children have at least one obese parent, and some of them have one parent who had undergone bariatric surgery (“bariatric families”). The perceptions and attitudes towards child obesity of parents in bariatric families vs. non-bariatric families have not been explored. We assessed how parents who underwent bariatric surgery for obesity perceived their child’s obesity compared to those perceptions of obese parents who did not undergo bariatric surgery.

Methods

We conducted a cross-sectional survey by interviewing families in which one or both parents underwent bariatric surgery (bariatric group) and comparing their responses to those of families in which one or both parents had been treated conservatively for obesity (control group). The children of both groups were attending the Obesity Clinic of our children’s hospital.

Results

Thirty-six children (median age 10.6 years, 18 in each group, matched for age and sex) were recruited. More parents in the bariatric group replied that weight plays an important role in determining self-image (p < 0.03), and more replied that their child’s obesity is a current and future health problem (p < 0.03 and p < 0.007, respectively, Table 1). Five children (28%) in the bariatric group had expectations of undergoing bariatric surgery compared to none in the control group (p < 0.02), with a similar trend among their parents (44% vs. 11%, respectively, p < 0.07).

Conclusion

Families in which one or both parents underwent bariatric surgery for obesity revealed different perceptions of their child’s obesity and different opinions about interventions for treating it compared to families with no bariatric surgery.
“Knock Knock”: a qualitative study exploring the experience of household contacts on home visits and their attitude towards people living with TB in South Africa
Authors: Sathar Farzana , Velen Kavindhran , Peterson Meaghan , Charalambous Salome , Chetty-Makkan Candice M.
Published: July 2020

Background

Household contract tracing (HHCT) is an important strategy for active tuberculosis case finding and offers an opportunity for testing of other diseases such as HIV. However, there is limited data on the patient-centered approach to HHCT. Our study aimed to describe experiences and preferences of household contacts (HHCs) for HHCT.

Methods

We conducted a qualitative study in Rustenburg, South Africa from September 2013 to March 2015. Twenty-four HHCs (≥18 years) had audio-recorded in-depth interviews. We used an inductive thematic analysis approach to develop themes. We made an a priori assumption that we would reach saturation with at least 20 interviews.

Results

There were 16 (66.7%) females (median age = 36 years) and eight (33.3%) males (median age = 34 years). Two themes developed: (i) Positive attitude of HHCs towards TB services provided at home and (ii) HHCs relationship to and acceptance of people living with TB (PLTB). The first main theme emphasized that HHCs appreciated the home visits. Participants preferred home visits because they had negative experiences at the clinic such as delayed waiting times and long queues. HHCs supported the screening of children for TB at home. Participants suggested that the research staff could expand their services by screening for diabetes and hypertension alongside TB screening. In the second main theme, there was a sense of responsibility from the HHCs towards accepting the diagnosis of PLTB and caring for them. A sub-theme that emerged was that as their knowledge on TB disease improved, they accepted the TB status of the PLTB empowering them to take care of the PLTB.

Conclusions

HHCs are supportive of HHCT and felt empowered by receiving TB education that ultimately allowed them to better understand and care for PLTB. HHCs were supportive of screening children for TB at home. Future HHCT activities should consider raising community awareness on the benefits of TB contact tracing at households.
Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women
Authors: Sun Wei , Qin Xueyun , Zhou Jing , Xu Mingjing , Lyu Zhangyan , Li Xin , Zhang Kai , Dai Min , Li Ni , Hang Dong
Published: July 2020

Background

Although human papillomavirus (HPV) infection has been regarded as the cause of cervical cancer in over 99% of cases, only a small fraction of HPV-infected women develop this malignancy. Emerging evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may contribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains undetermined.

Methods

The current study included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assays, and logistic regression analysis was performed to compute odds ratios (ORs) and 95% confidence intervals (CIs). Interaction between mtCN and HPV types was assessed by using the Wald test in logistic regression models.

Results

HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls (1.63 vs. 1.23, P = 0.03). After adjustment for age and HPV types, the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed (Ptrend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant.

Conclusions

In women who test HPV positive, the increase of mtCN in cervical exfoliated cells is associated with cervical cancer. This suggests a potential role of mtCN in cervical carcinogenesis.
Pharmacovigilance in healthcare education: students’ knowledge, attitude and perception: a cross-sectional study in Saudi Arabia
Authors: Alwhaibi Monira , Alhindi Ghaida , Alshamrani Majd , Essa Maryam Bin , A. Al Aloola Noha , Alhawassi Tariq M.
Published: July 2020

Background

Medication safety and pharmacovigilance (PV) remains as an important discipline worldwide. However, there is a significant lack of knowledge of PV and adverse drug reaction (ADR) reporting among students in the healthcare field. Thus, this study is aimed to measure knowledge, attitude, and perceptions and compares it between healthcare students (i.e., medicine, dentistry, and nursing).

Methods

A cross-sectional study involving 710 undergraduate healthcare students from different universities in Saudi Arabia was conducted. A validated structured pilot-tested questionnaire was administered to the participants to assess their knowledge, attitude, and perceptions towards PV and ADRs reporting. Descriptive statistics were used to describe the study findings. Data were analyzed using SPSS version 21.

Results

Overall, the study found that 60.8 and 40.0% of healthcare students correctly defined PV and ADRs respectively. Most students showed positive attitudes and perceptions towards PV and ADRs reporting. PV knowledge, attitude, and perceptions towards PV were significantly higher among pharmacy students as compared to other healthcare students. Only 39% of healthcare students revealed that they have received any form of PV education and 49% of them indicated that PV is well covered in their school curriculum. Pharmacy students are more trained in their schools to report and have performed ADRs reporting in their school as compared to other healthcare students.

Conclusions

Pharmacy students have better knowledge, attitude, and perception towards PV and ADR reporting in comparison to other healthcare students. The study clearly describes the need for integrating pharmacovigilance education in Saudi healthcare schools’ curriculums to prepare them for real-world practices and workplaces.
Relationship between oxygen consumption and neuronal activity in a defined neural circuit
Authors: Özugur Suzan , Kunz Lars , Straka Hans
Published: July 2020

Background

Neuronal computations related to sensory and motor activity along with the maintenance of spike discharge, synaptic transmission, and associated housekeeping are energetically demanding. The most efficient metabolic process to provide large amounts of energy equivalents is oxidative phosphorylation and thus dependent on O2 consumption. Therefore, O2 levels in the brain are a critical parameter that influences neuronal function. Measurements of O2 consumption have been used to estimate the cost of neuronal activity; however, exploring these metabolic relationships in vivo and under defined experimental conditions has been limited by technical challenges.

Results

We used isolated preparations of Xenopus laevis tadpoles to perform a quantitative analysis of O2 levels in the brain under in vivo-like conditions. We measured O2 concentrations in the hindbrain in relation to the spike discharge of the superior oblique eye muscle-innervating trochlear nerve as proxy for central nervous activity. In air-saturated bath Ringer solution, O2 levels in the fourth ventricle and adjacent, functionally intact hindbrain were close to zero. Inhibition of mitochondrial activity with potassium cyanide or fixation of the tissue with ethanol raised the ventricular O2 concentration to bath levels, indicating that the brain tissue consumed the available O2. Gradually increasing oxygenation of the Ringer solution caused a concurrent increase of ventricular O2 concentrations. Blocking spike discharge with the local anesthetics tricaine methanesulfonate diminished the O2 consumption by ~ 50%, illustrating the substantial O2 amount related to neuronal activity. In contrast, episodes of spontaneous trochlear nerve spike bursts were accompanied by transient increases of the O2 consumption with parameters that correlated with burst magnitude and duration.

Conclusions

Controlled experimental manipulations of both the O2 level as well as the neuronal activity under in vivo-like conditions allowed to quantitatively relate spike discharge magnitudes in a particular neuronal circuitry with the O2 consumption in this area. Moreover, the possibility to distinctly manipulate various functional parameters will yield more insight in the coupling between metabolic and neuronal activity. Thus, apart from providing quantitative empiric evidence for the link between physiologically relevant spontaneous spike discharge in the brain and O2-dependent metabolism, isolated amphibian preparations are promising model systems to further dissociate the O2 dynamics in relation to neuronal computations.
Correction to: Circular RNA profiling and its potential for esophageal squamous cell cancer diagnosis and prognosis
Authors: Fan Liyuan , Cao Qiang , Liu Jia , Zhang Junpeng , Li Baosheng
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
Assessment of dynamic balancing responses following perturbations during slow walking in relation to clinical outcome measures for high-functioning post-stroke subjects
Authors: Zadravec Matjaž , Olenšek Andrej , Rudolf Marko , Bizovičar Nataša , Goljar Nika , Matjačić Zlatko
Published: July 2020

Background

Generating appropriate balancing reactions in response to unexpected loss of balance during walking is important to prevent falls. The purpose of this study was to assess dynamic balancing responses following pushes to the pelvis in groups of post-stroke and healthy subjects.

Methods

Forty-one post-stroke subjects and forty-three healthy subjects participated in the study. Dynamic balancing responses to perturbations triggered at heel strike of the left or right leg, directed in the forward, backward, inward and outward directions during slow treadmill walking were assessed. Responses of the healthy group provided reference values used to classify responses of the post-stroke group into two subgroups; one within the reference responses (“inside” subgroup) and the other that falls out (“outside” subgroup). A battery of selected clinical outcome measures (6-Minute Walk Test, 10-Meter Walk Test, Timed-Up-and-Go test, Four Square Step Test, Functional Gait Assessment, Functional Independence Measure and One-legged stance test) was additionally assessed in the post-stroke group.

Results

The “inside” subgroup of post-stroke subjects was able to appropriately modulate centre-of-pressure and ground-reaction-force both under the impaired and non-impaired leg in response to perturbations. The “outside” subgroup of post-stroke subjects showed limited modulation of centre-of-pressure and ground-reaction-force under the impaired leg; instead stepping strategy was used in which the non-impaired leg was placed such as to make a longer step (forward perturbation), to make a shorter step (backward perturbation) or to make a cross-step (outward perturbation). Consequently, peak centre-of-mass displacements following perturbations were significantly higher in the “outside” subgroup compared to the “inside” subgroup. Responses in both subgroups following inward perturbations did not differ. Majority of clinical outcome measures moderately correlated with the peak centre-of-mass displacements for forward perturbations and exhibited weak correlations for other perturbation directions.

Conclusions

Substantial number of post-stroke subjects, that were considered to be independent walkers, have reduced capabilities to execute appropriate balancing responses following perturbations commencing on the hemiparetic leg and may thus benefit from perturbation-based training. Timed-Up-and-Go and Functional Independence Measure tests may provide an indication on the abilities of each subject to counteract unexpected loss of balance. However, a reliable assessment should be done through perturbation-based measures.
Correction to: West Nile virus in Europe: after action reviews of preparedness and response to the 2018 transmission season in Italy, Slovenia, Serbia and Greece
Authors: Riccardo Flavia , Bolici Francesco , Fafangel Mario , Jovanovic Verica , Socan Maja , Klepac Petra , Plavsa Dragana , Vasic Milena , Bella Antonino , Diana Gabriele , Rosi Luca , Pezzotti Patrizio , Andrianou Xanthi D. , Di Luca Marco , Venturi Giulietta , Maraglino Francesco , Pervanidou Danai , Cenciarelli Orlando , Baka Agoritsa , Young Johanna , Bakonyi Tamas , Rezza Giovanni , Suk Jonathan E.
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
Recent advances in CAR-T cell engineering
Authors: Huang Ruihao , Li Xiaoping , He Yundi , Zhu Wen , Gao Lei , Liu Yao , Gao Li , Wen Qin , Zhong Jiang F. , Zhang Cheng , Zhang Xi
Published: July 2020

Chimeric antigen receptor T (CAR-T) cell therapy is regarded as an effective solution for relapsed or refractory tumors, particularly for hematological malignancies. Although the initially approved anti-CD19 CAR-T therapy has produced impressive outcomes, setbacks such as high relapse rates and resistance were experienced, driving the need to discover engineered CAR-T cells that are more effective for therapeutic use. Innovations in the structure and manufacturing of CAR-T cells have resulted in significant improvements in efficacy and persistence, particularly with the development of fourth-generation CAR-T cells. Paired with an immune modifier, the use of fourth-generation and next-generation CAR-T cells will not be limited because of cytotoxic effects and will be an efficient tool for overcoming the tumor microenvironment. In this review, we summarize the recent transformations in the ectodomain, transmembrane domain, and endodomain of the CAR structure, which, together with innovative manufacturing technology and improved cell sources, improve the prospects for the future development of CAR-T cell therapy.
Correction to: Reproducibility of foot dimensions measured from 3‐dimensional foot scans in children and adolescents with Down syndrome
Authors: Hassan Nirmeen M. , Buldt Andrew K. , Shields Nora , Landorf Karl B. , Menz Hylton B. , Munteanu Shannon E.
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
meQTL and ncRNA functional analyses of 102 GWAS-SNPs associated with depression implicate HACE1 and SHANK2 genes
Authors: Ciuculete Diana M. , Voisin Sarah , Kular Lara , Jonsson Jörgen , Rask-Andersen Mathias , Mwinyi Jessica , Schiöth Helgi B.
Published: July 2020

Background

Little is known about how genetics and epigenetics interplay in depression. Evidence suggests that genetic variants may change vulnerability to depression by modulating DNA methylation (DNAm) and non-coding RNA (ncRNA) levels. Therefore, the aim of the study was to investigate the effect of the genetic variation, previously identified in the largest genome-wide association study for depression, on proximal DNAm and ncRNA levels.

Results

We performed DNAm quantitative trait locus (meQTL) analysis in two independent cohorts (total n = 435 healthy individuals), testing associations between 102 single-nucleotide polymorphisms (SNPs) and DNAm levels in whole blood. We identified and replicated 64 SNP-CpG pairs (padj. < 0.05) with meQTL effect. Lower DNAm at cg02098413 located in the HACE1 promoter conferred by the risk allele (C allele) at rs1933802 was associated with higher risk for depression (praw = 0.014, DNAm = 2.3%). In 1202 CD14+ cells sorted from blood, DNAm at cg02088412 positively correlated with HACE1 mRNA expression. Investigation in postmortem brain tissue of adults diagnosed with major depressive disorder (MDD) indicated 1% higher DNAm at cg02098413 in neurons and lower HACE1 mRNA expression in CA1 hippocampus of MDD patients compared with healthy controls (p = 0.008 and 0.012, respectively). Expression QTL analysis in blood of 74 adolescent revealed that hsa-miR-3664-5p was associated with rs7117514 (SHANK2) (padj. = 0.015, mRNA difference = 5.2%). Gene ontology analysis of the miRNA target genes highlighted implication in neuronal processes.

Conclusions

Collectively, our findings from a multi-tissue (blood and brain) and multi-layered (genetic, epigenetic, transcriptomic) approach suggest that genetic factors may influence depression by modulating DNAm and miRNA levels. Alterations at HACE1 and SHANK2 loci imply potential mechanisms, such as oxidative stress in the brain, underlying depression. Our results deepened the knowledge of molecular mechanisms in depression and suggest new epigenetic targets that should be further evaluated.
Socio-economic disparities and returning to work following an injury
Authors: Savitsky Bella , Radomislensky Irina , Goldman Sharon , Gitelson Natalia , Frid Zhanna , Peleg Kobi
Published: July 2020

Background

Traumatic injury is one of the main reasons for temporary and permanent occupational disability.

The objective of this study was to define the role of socio-economic position on post-injury occupational absenteeism.

Methods

This was a nationwide retrospective cohort study, based on linking The Israeli National Trauma Registry (INTR) and the National Insurance Institute (NII) databases.

The study population included 44,740 injured workers (residents of Israel, aged 21–67, hospitalized between 2008 and 2013 and employed prior to injury as salaried workers). Logistic-regression models tested the probability of not returning to work (RTW).

Results

The majority of the study population (61%) RTW within 1 month following the injury event. Income prior to injury was significantly associated with longer out of work stay, explaining 9% variance. A significant interaction (p value < 0.0001) was found between age and income on out of work stay more than 1 month, 1 year and 2 years. Logistic regression models of out of work stay were conducted separately for all age groups. Lower income was associated with greater chance for out of work stay for more than 1 month; and the gap between the lowest and highest income quartiles was greater among older workers (age 55+), where there was an elevenfold increase in probability of not RTW among casualties from the lowest vs. highest income quartile. In comparison to other population groups, Arabs were at greater odds of longer out of work stay following an injury. Among injured persons recognized by the NII as having occupational injuries, the odds for not RTW within a month, a year and 2 years were respectively 3.9, 2.5 and 2.2 times significantly greater in comparison to employees injured outside the workplace.

Conclusions

This study identified population groups with a high probability of not RTW following an injury requiring hospitalization. Intervention programs for injured employees should promote early rehabilitation and aim to shorten out of work stay. These programs should be ethnically adapted and focus on underprivileged and disadvantaged populations.
Controllability of fractional evolution systems of Sobolev type via resolvent operators
Authors: Yang He , Zhao Yanjie
Published: July 2020

In this paper, we consider the nonlocal controllability of $\alpha\in (1,2)$
α
∈
(
1
,
2
)
-order fractional evolution systems of Sobolev type in abstract spaces. By utilizing fixed point theorems and the theory of resolvent operators we establish some sufficient conditions for the nonlocal controllability of Sobolev-type fractional evolution systems.
A specialised finite element for simulating self-healing quasi-brittle materials
Authors: Freeman Brubeck L. , Bonilla-Villalba Pedro , Mihai Iulia C. , Alnaas Waled F. , Jefferson Anthony D.
Published: July 2020

A new specialised finite element for simulating the cracking and healing behaviour of quasi-brittle materials is presented. The element employs a strong discontinuity approach to represent displacement jumps associated with cracks. A particular feature of the work is the introduction of healing into the element formulation. The healing variables are introduced at the element level, which ensures consistency with the internal degrees freedom that represent the crack; namely, the crack opening, crack sliding and rotation. In the present work, the element is combined with a new cohesive zone model to simulate damage-healing behaviour and implemented with a crack tracking algorithm. To demonstrate the performance of the new element and constitutive models, a convergence test and two validation examples are presented that consider the response of a vascular self-healing cementitious material system for three different specimens. The examples show that the model is able to accurately capture the cracking and healing behaviour of this type of self-healing material system with good accuracy.