bluuebunny/crossref_metadata_2025 huggingface dataset:
The JNK pathway represents a novel target in the treatment of rheumatoid arthritis through the suppression of MMP-3
Authors: Kanai Tomotake , Kondo Naoki , Okada Masayasu , Sano Hiroshige , Okumura Go , Kijima Yasufumi , Ogose Akira , Kawashima Hiroyuki , Endo Naoto
Published: March 2020

Background and aim

The pathophysiology of rheumatoid arthritis (RA) is characterized by excess production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) by neutrophils and macrophages in synovium. Additionally, these cytokines promote the production of reactive oxygen species (ROS), and increased production of matrix metalloproteinases (MMPs), including MMP-3, in synoviocytes that result in joint destruction. There is limited information on how proteolytic enzymes such as MMP-3 can be regulated. We evaluated the effect of the antioxidant N-acetylcysteine (NAC) on RA and identified the relationship between the c-Jun N terminal kinase (JNK) pathway and MMP-3. We hypothesized that elucidating this relationship would lead to novel therapeutic approaches to RA treatment and management.

Methods

We investigated the effect of administering a low dose (1000 μM or less) of an antioxidant (NAC) to human rheumatoid fibroblast-like synoviocytes (MH7A cells). We also investigated the response of antioxidant genes such as nuclear factor erythroid -derived 2-related factor 2 (Nrf2) and Sequestosome 1 (p62). The influence of MMP-3 expression on the JNK pathway leading to joint destruction and the mechanisms underlying this relationship were investigated through primary dispersion culture cells collected from the synovial membranes of RA patients, consisting of rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS).

Results

Low-dose NAC (1000 μM) increased the expression of Nrf2 and phospho-p62 in MH7A cells, activating antioxidant genes, suppressing the expression of MMP-3, and inhibiting the phosphorylation of JNK. ROS, MMP-3 expression, and IL-6 was suppressed by administering 30 μM of SP600125 (a JNK inhibitor) in MH7A cells. Furthermore, the administration of SP600125 (30 μM) to RA-FLS suppressed MMP-3.

Conclusions

We demonstrated the existence of an MMP-3 suppression mechanism that utilizes the JNK pathway in RA-FLS. We consider that the JNK pathway could be a target for future RA therapies.
Quality indicators for patients with traumatic brain injury in European intensive care units: a CENTER-TBI study
Authors:   the CENTER-TBI investigators and participants for the ICU stratum, Huijben Jilske A. , Wiegers Eveline J. A. , Ercole Ari , de Keizer Nicolette F. , Maas Andrew I. R. , Steyerberg Ewout W. , Citerio Giuseppe , Wilson Lindsay , Polinder Suzanne , Nieboer Daan , Menon David , Lingsma Hester F. , van der Jagt Mathieu
Published: March 2020

Background

The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measurement and improvement.

Methods

Our analysis was based on 2006 adult patients admitted to 54 ICUs between 2014 and 2018, enrolled in the CENTER-TBI study. Indicator scores were calculated as percentage adherence for structure and process indicators and as event rates or median scores for outcome indicators. Feasibility was quantified by the completeness of the variables. Discriminability was determined by the between-centre variation, estimated with a random effect regression model adjusted for case-mix severity and quantified by the median odds ratio (MOR). Statistical uncertainty of outcome indicators was determined by the median number of events per centre, using a cut-off of 10.

Results

A total of 26/42 indicators could be calculated from the CENTER-TBI database. Most quality indicators proved feasible to obtain with more than 70% completeness. Sub-optimal adherence was found for most quality indicators, ranging from 26 to 93% and 20 to 99% for structure and process indicators. Significant (p < 0.001) between-centre variation was found in seven process and five outcome indicators with MORs ranging from 1.51 to 4.14. Statistical uncertainty of outcome indicators was generally high; five out of seven had less than 10 events per centre.

Conclusions

Overall, nine structures, five processes, but none of the outcome indicators showed potential for quality improvement purposes for TBI patients in the ICU. Future research should focus on implementation efforts and continuous reevaluation of quality indicators.

Trial registration

The core study was registered with ClinicalTrials.gov, number NCT02210221, registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).
A multicenter randomized trial of personalized acupuncture, fixed acupuncture, letrozole, and placebo letrozole on live birth in infertile women with polycystic ovary syndrome
Authors: Huang Shiya , Hu Min , Ng Ernest Hung Yu , Stener-Victorin Elisabet , Zheng Yanhua , Wen Qidan , Wang Cong , Lai Maohua , Li Juan , Gao Xingcheng , Wang Xinhua , Hu Zhenxing , Xia Tian , Hu Rongkui , Liu Jianping , Wen Xiaohui , Li Shuna , Quan Kewei , Liang Xingyan , Shang Hongcai , Ma Hongxia , Qiao Jie
Published: March 2020

Background

Traditional Chinese medicine (TCM) usually involves syndrome differentiation and treatment. Acupuncture, one form of TCM, requires the selection of appropriate acupoints and needling techniques, but many clinical trials on acupuncture have used fixed acupuncture protocols without accounting for individual patient differences. We have designed a multicenter randomized controlled trial (RCT) to evaluate whether personalized or fixed acupuncture increases the likelihood of live births in infertile women with polycystic ovary syndrome (PCOS) compared with letrozole or placebo letrozole. We hypothesize that letrozole is more effective than personalized acupuncture, which in turn is more effective than fixed acupuncture, and that placebo letrozole is the least effective intervention. Moreover, we hypothesize that personalized acupuncture is more likely to reduce the miscarriage rate and the risk of pregnancy complications compared with letrozole.

Methods/design

The study is designed as an assessor-blinded RCT. A total of 1100 infertile women with PCOS will be recruited from 28 hospitals and randomly allocated to 4 groups: personalized acupuncture, fixed acupuncture, letrozole, or placebo letrozole. They will receive treatment for 16 weeks, and the primary outcome is live birth. Secondary outcomes include ovulation rate, conception rate, pregnancy rate, pregnancy loss rate, changes in hormonal and metabolic parameters, and changes in quality of life scores. Adverse events will be recorded throughout the trial. All statistical analyses will be performed using IBM SPSS Statistics version 21.0 software (IBM Corp., Armonk, NY, USA), and a P value < 0.05 will be considered statistically significant.

Discussion

This study will be the first multicenter RCT to compare the effect of personalized or fixed acupuncture with letrozole or placebo letrozole on live birth in infertile women with PCOS. The findings will inform whether personalized acupuncture therapy can be considered an alternative treatment to improve the live birth rate in infertile women with PCOS.

Trial registration

ClinicalTrials.gov, NCT03625531. Registered on July 13, 2018.

Chinese Clinical Trial Registry, ChiCTR1800017304. Registered on July 23, 2018.
Verifying participant-reported clinical outcomes: challenges and implications
Authors: Breeman Suzanne , Constable Lynda , Duncan Anne , Starr Kath , McDonald Alison , Wileman Samantha , Cotton Seonaidh
Published: March 2020

Background

Researchers often rely on trial participants to self-report clinical outcomes (for example, fractures, re-operations). Little information exists as to the ‘accuracy’ of participant-reported clinical outcomes, particularly in randomised controlled trials (RCTs). To help address this evidence gap, we report four case studies, nested within different RCTs where participant-reported clinical outcome data were compared with those reported by clinicians or extracted from medical notes.

Methods

Four publicly-funded RCTs with different methods of verifying participant-reported outcomes were identified. In KAT, the participants were asked about hospital admissions for any reason. Where it was thought to be relevant to the trial knee, further information was sought from the lead surgeon at the admitting site to confirm whether or not the admission was relevant to the trial knee. In REFLUX, participants were asked about hospital admissions for any reason. For participants who reported a re-operation, further information was sought from the lead surgeon at the admitting site to confirm this. In RECORD, participants were asked three questions regarding broken bones. Where low-trauma fractures were reported, clinical verification was sought, initially from the research nurse at the site.

In CATHETER, participants were asked about urinary tract infections (UTIs), and a prescription of antibiotics was provided for the treatment of UTIs following urethral catheterisation. The GPs of those who reported a UTI were contacted to confirm that an antibiotic prescription had been issued for the suspected UTI.

Results

In KAT, 397 of 6882 (6%) participant-reported hospital admissions were confirmed as relevant to the trial knee. In REFLUX, 16 of 19 participants (84%) who appeared to have had a re-operation were confirmed as having had one. In RECORD, 473 of 781 (61%) fractures reported by participants were confirmed as being low-trauma fractures. In CATHETER, 429 of 830 participant-reported UTIs (52%) were confirmed as such by the GPs.

Conclusions

We used different approaches in our verification of participant-reported outcomes in clinical trials, and we believe there is no one optimal solution. Consideration of issues such as what information is sought from participants, the phrasing of questions, whether the medical records are a true ‘gold standard’ and costs and benefits to the RCT may help determine the appropriate approach.
Giving radiologists a voice: a review of podcasts in radiology
Authors: Clarke Christopher G. D. , Nnajiuba Uzoma , Howie Jamie , Khan Muhammad , Pinto dos Santos Daniel , Ranschaert Erik
Published: March 2020

Objectives

Podcasts are audio recordings distributed via the Internet. We review the availability of podcasts on the topic of radiology.

Methods

A search for podcasts relating to radiology was performed using search engines and free public websites that either hosted or distributed podcasts. Only English language podcast series were included, and video podcasts were excluded. Data was gathered by manually interrogating the metadata on the primary hosting platform and related websites.

Results

Forty-one podcast series met the inclusion criteria. The earliest was from 2005. In total, 56.1% of podcasts were defined as active and 43.9% inactive at the time of publication. Number of episodes for each podcast series ranged from 1 to 269 with 56.1% of podcasts having ≤ 10 episodes. There was a wide variation in podcast series’ frequency/schedules. The most common subject topic was ‘radiology current affairs’ (43.9%), with the least common ‘exam revision’ (7.3%) and ‘radiography’ (7.3%). The majority of podcasts were targeted at radiologists (87.8%) and originated from the USA (70.1%). Podcast hosts consisted of doctors (63.4%), other professionals (29.3%) or unknown (7.3%). Additional supplementary media or information as show notes were provided by 26.8% of radiology podcast series.

Conclusions

This gives a new insight into the world of ‘radiology podcasting’. To the authors’ knowledge, this is the first review in the literature and highlights the increasing availability of podcasting in radiology.
Priming with inflammatory cytokines is not a prerequisite to increase immune-suppressive effects and responsiveness of equine amniotic mesenchymal stromal cells
Authors: Lange-Consiglio Anna , Romele Pietro , Magatti Marta , Silini Antonietta , Idda Antonella , Martino Nicola Antonio , Cremonesi Fausto , Parolini Ornella
Published: March 2020

Background

Equine amniotic mesenchymal stromal cells (AMSCs) and their conditioned medium (CM) were evaluated for their ability to inhibit in vitro proliferation of peripheral blood mononuclear cells (PBMCs) with and without priming. Additionally, AMSC immunogenicity was assessed by expression of MHCI and MHCII and their ability to counteract the in vitro inflammatory process.

Methods

Horse PBMC proliferation was induced with phytohemagglutinin. AMSC priming was performed with 10 ng/ml of TNF-α, 100 ng/ml of IFN-γ, and a combination of 5 ng/ml of TNF-α and 50 ng/ml of IFN-γ.

The CM generated from naïve unprimed and primed AMSCs was also tested to evaluate its effects on equine endometrial cells in an in vitro inflammatory model induced by LPS. Immunogenicity marker expression (MHCI and II) was evaluated by qRT-PCR and by flow cytometry.

Results

Priming does not increase MHCI and II expression. Furthermore, the inhibition of PBMC proliferation was comparable between naïve and conditioned cells, with the exception of AMSCs primed with both TNF-α and IFN-γ that had a reduced capacity to inhibit T cell proliferation. However, AMSC viability was lower after priming than under other experimental conditions. CM from naïve and primed AMSCs strongly inhibited PBMC proliferation and counteracted the inflammatory process, rescuing about 65% of endometrial cells treated by LPS.

Conclusion

AMSCs and their CM have a strong capacity to inhibit PBMC proliferation, and priming is not necessary to improve their immunosuppressive activity or reactivity in an inflammatory in vitro model.
Characterization of dendritic cells and follicular dendritic cells in the hepatic lymph nodes and liver of sheep experimentally infected with Fasciola hepatica
Authors: Ruiz-Campillo María Teresa , Molina-Hernández Verónica , Bautista María José , Pacheco Isabel L. , Zafra Rafael , Buffoni Leandro , Martínez-Moreno Francisco Javier , Martínez-Moreno Alvaro , Pérez José
Published: March 2020

Fasciola hepaticahas been shown to have a high capacity for immunomodulation of the host response, making the development of protective vaccines extremely difficult. One of these immunomodulation mechanisms is the impairment of dendritic cells (DC) maturation and, therefore, suppression of antigenic presentation. The aim of this study was to evaluate the pathological changes as well as the characterization of two antigen presenting cells, DC (CD1b, CD83 and MHC-II positive) and follicular dendritic cells (FDC) (CNA.42, S100 and CD83 positive) by immunohistochemistry in the hepatic lymph nodes (HLN) and livers of sheep during the early stages of infection withF. hepatica[9 and 18 days post-infection (dpi)], compared with an uninfected group (UC) as a control. The results revealed a marked hyperplasia of HLN germinal centres at 9 and, in particular, 18 dpi, with respect to the UC group, with coincidental increased expression of CNA.42 in FDC of lymphoid follicles and CD1b in the DC of paracortical areas at 18 dpi. However, the expression of MHC-II and CD83 decreased at 9 and, particularly, at 18 dpi in HLN compared with that in the UC group. Since both markers are related to active presentation of antigens by DC and FDC, the results of the present study suggest that, despite the marked hyperplasia of HLN and increase in DC and FDC numbers during early stages of infection, the DC and FDC antigenic presentation capacity, as suggested by the expression of the markers MHC-II and CD83, is suppressed by the parasite. This suppression was not observed in the liver, probably because of the low number of DC. This is the first study of the immunophenotype of DCs and FDC in sheep infected withF. hepatica.
Risk factors of obstructive sleep apnea syndrome in children
Authors: Xu Zhifei , Wu Yunxiao , Tai Jun , Feng Guoshuang , Ge Wentong , Zheng Li , Zhou Zhe , Ni Xin
Published: March 2020

Background

The known risk factors of childhood OSAS include tonsillar and adenoidhypertrophy, obesity, craniofacial anomalies, neuromuscular disorders and African-American (AA) ancestry. Whether other factors such as allergic rhinitis (AR), premature, environmental tobacco smoking (ETS) are associated with OSAS are inconsistent in different studies. Our study enrolled children of a broad age range and included potential risk factors of OSAS derived from previous studies and our own experience. Our objective is to identify risk factors of OSAS in children in a clinical setting.

Methods

Children between 2 and 15 years of age exhibiting snoring symptoms who visited the sleep center for polysomnography (PSG) were enrolled. All children completed a questionnaire, physical examination and PSG. The questionnaire included demographic data and information related to potential risk factors for sleep disorders. A physical examination included measurements of height, weight, neck circumference, waist and hip ratio, visual evaluation of the tonsils and the degree of adenoid obstruction. Children with obstructive apnea-hypopnea index (OAHI) ≥ 1 were defined as OSAS.

Results

A total of 1578 children were enrolled and1009 children exhibited OSAS. Univariate analyses showed that snoring occurring for ≥ 3 months, male gender, preterm birth, breastfeeding, obesity, neck circumference ≥ 30 cm, waist/hip ratio ≥ 0.95, tonsillar hypertrophy, and adenoid hypertrophy were associated with OSAS. The proportion of low educational level was higher in parents who breastfed their babies than those who didn't. Multivariate analysis showed that snoring for ≥ 3 months, male gender, obesity, breastfeeding, tonsillar hypertrophy, and adenoid hypertrophy were associated with OSAS. Confounders such as socioeconomic status, parental occupation, and health-related behaviors should be explored further to investigate the relationship between breastfeeding and OSAS.

Conclusion

The independent risk factors for OSAS in children included snoring ≥ 3 months, male gender, obesity, breastfeeding, tonsillar and adenoid hypertrophy. The study was registered on Clinical Trials government (NCT02447614). The name of the trial is “Follow-up Studies of Primary Snoring (PS) and Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) in Chinese Children” and the URL is https://clinicaltrials.gov/ .
Inelastic behavior and mechanical strength of the shallow upper crust controlled by layer-parallel slip in the high-strain zone of the Niigata region, Japan
Authors: Otsubo Makoto , Katayama Ikuo , Miyakawa Ayumu , Sagiya Takeshi
Published: March 2020

We investigated the relationship between contractional deformation of sedimentary mass in the upper crust and the geodetic strain rate in a high-strain zone (part of the Niigata–Kobe Tectonic Zone) of the mid-Niigata region, Central Japan. We observed numerous examples of layer-parallel slip (bedding-plane slip) generated by folding. The slip layers have an average spacing of ~ 3.6 m (measured normal to bedding planes) at the Katagai site. In shallow sedimentary units of the upper crust, numerous bedding-plane slip events act to reduce the mechanical strength (effective elastic thickness) of sedimentary rocks under contractional deformation. The results support an existing model, based on geodetic observations, of mechanical decoupling between the weak sedimentary layers and basement. On the layer-parallel slip, we measured the friction coefficient of gouge generated by bedding-plane slip and of mud around non-slip surfaces using double-direct shear tests, and found no difference in frictional coefficient between slip and non-slip surfaces.
Impact of atherosclerotic cardiovascular disease on healthcare resource utilization and costs in patients with type 2 diabetes mellitus in a real-world setting
Authors: Weng Wayne , Tian Ye , Kong Sheldon X. , Ganguly Rahul , Hersloev Malene , Brett Jason , Hobbs Todd
Published: March 2020

Background

This study evaluated the impact of atherosclerotic cardiovascular disease (ASCVD) on healthcare resource utilization and costs in patients with type 2 diabetes mellitus (T2DM).

Methods

This study was a retrospective, cross-sectional study using US claims data. Adult patients with T2DM were stratified by presence or absence of ASCVD and compared regarding annual (2015) healthcare resource utilization and associated costs. Subgroup analyses were conducted for three age groups (18–44, 45–64, and ≥ 65 years).

Results

Among 1,202,596 eligible patients with T2DM, 45.2% had documented ASCVD. The proportions of patients with inpatient and ER-based resource utilization during 2015 were three-to-four times greater in the ASCVD cohort as compared to the non-ASCVD cohort for the categories of inpatient visits (15.6% vs 4.4% of patients), outpatient ER visits (18.4% vs 5.2% of patients), and inpatient ER visits (4.3% vs 0.9% of patients). Outpatient utilization also was higher among patients with ASCVD as compared to those without ASCVD (mean number of annual office visits per patient, 9.1 vs 5.6), and more than twice as many patients with ASCVD had ≥ 9 office visits (43.5% vs 19.8%). Average per-patient total healthcare cost was $22,977 for ASCVD vs $9735 for non-ASCVD, with medical costs primarily driving the difference ($17,849 vs $6079); the difference in pharmacy costs was smaller ($5128 vs $3656). In the 18–44, 45–64, and ≥ 65 age subgroups respectively, total annual healthcare costs were 143, 127, and 114% higher in ASCVD vs non-ASCVD patients.

Conclusions

These findings indicate significantly higher healthcare resource utilization and associated costs in patients having T2DM with ASCVD compared to T2DM without ASCVD.
Data and research to inform global policy: the global compact for safe, orderly and regular migration
Authors: Kraly Ellen Percy , Hovy Bela
Published: March 2020

In December 2018, the UN General Assembly formerly endorsed the Global Compact for Safe, Orderly and Regular Migration. Louise Arbour, Special Representative of the Secretary-General for International Migration, said, “the formal endorsement of the Compact represents a resounding commitment to an international migration framework based on fact, not myth, and to an understanding that national migration policies are best implemented through cooperation not in isolation.” While there are formidable challenges to the implementation of the Compact, the mandates for the role of evidence in policy and program formulation have been expressed from stakeholders, Member States, civil society organizations, and migrants, throughout the preparatory processes. This paper seeks to share those voices vis a vis the call for research concerning data, research and analysis concerning international migrants and displaced persons, and will consider the implications for scientific initiatives for migration research and analysis and for global policy and goals concerning migration and sustainable development.
17-Gene Genomic Prostate Score Test Results in the Canary Prostate Active Surveillance Study (PASS) Cohort
Authors: Lin Daniel W. , Zheng Yingye , McKenney Jesse K. , Brown Marshall D. , Lu Ruixiao , Crager Michael , Boyer Hilary , Tretiakova Maria , Brooks James D. , Dash Atreya , Fabrizio Michael D. , Gleave Martin E. , Kolb Suzanne , Liss Michael , Morgan Todd M. , Thompson Ian M. , Wagner Andrew A. , Tsiatis Athanasios , Pingitore Andrea , Nelson Peter S. , Newcomb Lisa F.
Published: March 2020

PURPOSE

The 17-gene Onco type DX Genomic Prostate Score (GPS) test predicts adverse pathology (AP) in patients with low-risk prostate cancer treated with immediate surgery. We evaluated the GPS test as a predictor of outcomes in a multicenter active surveillance cohort.

MATERIALS AND METHODS

Diagnostic biopsy tissue was obtained from men enrolled at 8 sites in the Canary Prostate Active Surveillance Study. The primary endpoint was AP (Gleason Grade Group [GG] ≥ 3, ≥ pT3a) in men who underwent radical prostatectomy (RP) after initial surveillance. Multivariable regression models for interval-censored data were used to evaluate the association between AP and GPS. Inverse probability of censoring weighting was applied to adjust for informative censoring. Predictiveness curves were used to evaluate how models stratified risk of AP. Association between GPS and time to upgrade on surveillance biopsy was evaluated using Cox proportional hazards models.

RESULTS

GPS results were obtained for 432 men (median follow-up, 4.6 years); 101 underwent RP after a median 2.1 years of surveillance, and 52 had AP. A total of 167 men (39%) upgraded at a subsequent biopsy. GPS was significantly associated with AP when adjusted for diagnostic GG (hazards ratio [HR]/5 GPS units, 1.18; 95% CI, 1.04 to 1.44; P = .030), but not when also adjusted for prostate-specific antigen density (PSAD; HR, 1.85; 95% CI, 0.99 to 4.19; P = .066). Models containing PSAD and GG, or PSAD, GG, and GPS may stratify risk better than a model with GPS and GG. No association was observed between GPS and subsequent biopsy upgrade ( P = .48).

CONCLUSION

In our study, the independent association of GPS with AP after initial active surveillance was not statistically significant, and there was no association with upgrading in surveillance biopsy. Adding GPS to a model containing PSAD and diagnostic GG did not significantly improve stratification of risk for AP over the clinical variables alone.
Unconventional Estrogen Signaling in Health and Disease
Authors: Faltas Christina L , LeBron Kira A , Holz Marina K
Published: March 2020

Estrogen is a key hormone involved in the development and homeostasis of several tissue types in both males and females. By binding estrogen receptors, estrogen regulates essential functions of gene expression, metabolism, cell growth, and proliferation by acting through cytoplasmic signaling pathways or activating transcription in the nucleus. However, disruption or dysregulation of estrogen activity has been shown to play a key role in the pathogenesis and progression of many diseases. This review will expatiate on some of the unconventional roles of estrogen in homeostasis and disease.
Inside Job or Deep Impact? Extramural Citations and the Influence of Economic Scholarship
Authors: Angrist Josh , Azoulay Pierre , Ellison Glenn , Hill Ryan , Lu Susan Feng
Published: March 2020

Does academic economic research produce material of general scientific value, or do academic economists write only for peers? Is economics scholarship uniquely insular? We address these questions by quantifying interactions between economics and other disciplines. Changes in the influence of economic scholarship are measured here by the frequency with which other disciplines cite papers in economics journals. We document a clear rise in the extramural influence of economic research, while also showing that economics is increasingly likely to reference other social sciences. A breakdown of extramural citations by economics fields shows broad field influence. Differentiating between theoretical and empirical papers classified using machine learning, we see that much of the rise in economics’ extramural influence reflects growth in citations to empirical work. This growth parallels an increase in the share of empirical cites within economics. At the same time, some disciplines that primarily cite economic theory have also recently increased citations of economics scholarship. ( JEL A11, A14)
Muscleblind-like 2 controls the hypoxia response of cancer cells
Authors: Fischer Sandra , Di Liddo Antonella , Taylor Katarzyna , Gerhardus Jamina S. , Sobczak Krzysztof , Zarnack Kathi , Weigand Julia E.
Published: March 2020

Hypoxia is a hallmark of solid cancers, supporting proliferation, angiogenesis, and escape from apoptosis. There is still limited understanding of how cancer cells adapt to hypoxic conditions and survive. We analyzed transcriptome changes of human lung and breast cancer cells under chronic hypoxia. Hypoxia induced highly concordant changes in transcript abundance, but divergent splicing responses, underlining the cell type-specificity of alternative splicing programs. While RNA-binding proteins were predominantly reduced, hypoxia specifically induced muscleblind-like protein 2 (MBNL2). Strikingly, MBNL2 induction was critical for hypoxia adaptation by controlling the transcript abundance of hypoxia response genes, such as vascular endothelial growth factor A (VEGFA). MBNL2 depletion reduced the proliferation and migration of cancer cells, demonstrating an important role of MBNL2 as cancer driver. Hypoxia control is specific for MBNL2 and not shared by its paralog MBNL1. Thus, our study revealed MBNL2 as central mediator of cancer cell responses to hypoxia, regulating the expression and alternative splicing of hypoxia-induced genes.
Frequency of impaired fasting glucose in first degree relatives of Type-II diabetic patients and its association with Body Mass Index
Authors: Muhammed Alia Ali , Taj Azeem , Ahmed Muhammed Uthman , Tabrez Elsa
Published: March 2020

Objectives: To determine the frequency of impaired fasting glucose in first degree relatives of people with Type-II diabetes and its association with BMI.

Methods: This cross-sectional study was conducted in Diabetic clinic of Shaikh Zayed Hospital, Lahore from July to December 2017. Individuals aged ≥35 years, first degree relatives of people with Type-II diabetes, were selected and their fasting blood glucose levels were checked twice a week apart. Study participants were divided into 3 groups. Group-I were those with normal fasting blood glucose (FBS: <100mg/dl), Group-II were those with impaired fasting glucose (100-125mg/dl), considered as high risk and Group-III included those who turned out to be having frank diabetes (FBS: ≥126mg/dl). Exclusion criteria were known diabetes and pregnancy. Proportions of impaired fasting glucose levels versus BMI were compared using Chi-square test. Significance was considered at P <0.001.

Results: A total of hundred subjects were included in the study with the mean age of 44.27 years. Sixty percent participants had normal FBS, 31% showed impaired FBS and 09% had frank diabetes (P <0.001). Significant association was found between impaired fasting glucose and BMI, as with increasing BMI the frequency of impaired fasting glucose increases.

Conclusion: First-degree relatives of people with Type-II diabetes showed higher frequency of impaired fasting glucose and obesity was an important risk factor.

doi: https://doi.org/10.12669/pjms.36.3.57

How to cite this:Ali A, Taj A, Ahmed MU, Tabrez E. Frequency of impaired fasting glucose in first degree relatives of Type-II diabetic patients and its association with Body Mass Index. Pak J Med Sci. 2020;36(3):407-411. doi: https://doi.org/10.12669/pjms.36.3.57

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Practice Prize Report: The 2018 ISMS Gary Lilien Practice Prize Competition
Authors: Roberts John H.
Published: March 2020

This report summarizes the entrants in the 2018 ISMS Gary Lilien Marketing Science Practice Prize Competition, designed to identify, encourage, recognize, and reward the application of impactful marketing science to industry and noncommercial settings. These applications aim to showcase innovative and impactful examples of applications demonstrating the best of rigor and relevance that our profession produces. The winner described an application of econometric and experimental techniques at the French-based retailer of body, face, fragrances, and home products, L’Occitane, aimed to optimize budget allocation between online and off-line marketing expenditure across six countries. The other three finalists include a decision support aid to assist members of the United Services Automobile Association (a not-for-profit organization to assist military service personnel select and finance their automobile purchases) choose vehicles that balance their individual tastes and preferences with their financial circumstances, a business-to-business pricing decision support aid for use by the sales force of Hadco Metal Trading to avoid loss of margin by undercharging and loss of business by overcharging, and a methodology to test online advertisements cost-effectively by generating “ghost ads” as a way of minimizing control group costs in a reliable and valid way.
Appointment Scheduling Under Time-Dependent Patient No-Show Behavior
Authors: Kong Qingxia , Li Shan , Liu Nan , Teo Chung-Piaw , Yan Zhenzhen
Published: March 2020

This paper studies how to schedule medical appointments with time-dependent patient no-show behavior and random service times. The problem is motivated by our studies of independent datasets from countries in two continents that unanimously identify a significant time-of-day effect on patient show-up probabilities. We deploy a distributionally robust model, which minimizes the worst-case total expected costs of patient waiting and service provider’s idling and overtime, by optimizing the scheduled arrival times of patients. This model is challenging because evaluating the total cost for a given schedule involves a linear program with uncertainties present in both the objective function and the right-hand side of the constraints. In addition, the ambiguity set considered contains discrete uncertainties and complementary functional relationships among these uncertainties (namely, patient no-shows and service durations). We show that when patient no-shows are exogenous (i.e., time-independent), the problem can be reformulated as a copositive program and then be approximated by semidefinite programs. When patient no-shows are endogenous on time (and hence on the schedule), the problem becomes a bilinear copositive program. We construct a set of dual prices to guide the search for a good schedule and use the technique iteratively to obtain a near-optimal solution. Our computational studies reveal a significant reduction in total expected cost by taking into account the time-of-day variation in patient show-up probabilities as opposed to ignoring it.

This paper was accepted by David Simchi-Levi, optimization.
Reflections of Research: the heart and brain axis
Authors: Tan Cheryl
Published: March 2020

The annual image competition, Reflections of Research, provides a glimpse into the cutting-edge heart and circulatory research funded by the British Heart Foundation
ECG of the month
Authors: Bloe Charlie
Published: March 2020

In this issue's ECG of the month, Charles Bloe presents the case of a 42-year-old man, admitted to hospital after having developed chest pain
The end of the rapid sequence induction?
Authors: Chen Mark , Carle Coralie
Published: March 2020

The rapid sequence induction has been a cornerstone of anaesthetic teaching since it was first described in 1970. Although the technique is taught as a standard protocol there is considerable variation in its practice. So, can we reach consensus over what to include in ‘the safe, textbook version’ of a rapid sequence induction in modern anaesthesia?
Non-contact optical sensing of vocal fold vibrations by secondary speckle patterns
Authors: Duadi Doron , Ozana Nisan , Shabairou Nadav , Wolf Michael , Zalevsky Zeev , Primov-Fever Adi
Published: March 2020

Vocal folds lesions are commonly diagnosed using an endoscopic-stroboscope. However, the stroboscopic picture of the vocal folds vibrations is subjectively and qualitatively evaluated by the clinician and, due to technical limitations, is unable to accurately distinguish between healthy and pathologic regions. In this paper, we propose two optical approaches for objectively sensing the vocal folds vibrations, using either external or internal laser illumination, based on temporal tracking of the reflected spatial distribution of secondary speckle patterns. The external configuration (the neck) is noninvasive and the internal configuration (the larynx) allows simultaneous extraction of data from multiple sites on the vocal folds. In this paper, we present measurements of healthy human subjects. Quantitative and precise measurements of vibration parameters of the vocal folds will enable a better understanding of hidden pathologies and optimize the diagnosis and treatment.
Influence of hepatic neoplasia on life expectancy in dogs
Authors: Vilkovyskiy I. F. , Vatnikov Yu A. , Kulikov E. V. , Sotnikova E. D. , Yagnikov S. A. , Seleznev S. B. , Krotova E. A. , Byakhova V. M. , Grishin V. N. , Avdotin V. P.
Published: March 2020

Background and Aim: The present study investigated the influence of liver tumor structure on life expectancy in dogs. Diseases of the liver comprise 5-25% of all non-communicable diseases in dogs, and primary hepatic tumors account for 0.6-1.3% of tumors. This research aimed to study the post-operative life span of animals with primary or metastatic tumors of the liver. Materials and Methods: During the study period, 7124 oncological operations were performed in our clinic. In total, 128 liver tumors were detected in live animals, while 323 were detected posthumously. Forty animals underwent surgery for various liver tumors. In dogs with primary liver tumors, the average age was 11.9 years and the average body weight was 15.5 kg, while in dogs with liver metastases, the mean age was 11.4 years and the average body weight was 24 kg. Results: The ratio of males to females among dogs with primary liver tumors was about 1:1 (ten females and nine males), while that among dogs with metastatic liver damage was clearly predominantly female (14 females and two males) because females often undergo surgery for cancerous mammary glands or ovaries. Conclusion: The size of tumors and the number of affected lobes had a significant effect on the post-operative life span. With a tumor size of <5 cm and a lesion covering less than two lobes of the liver, life expectancy was significantly longer and the prognosis was more favorable. In cases of large tumors or those affecting more than two lobes, life expectancy was significantly reduced and the prognosis was cautious to unfavorable.
Rovásírással – latinul
Authors: Fehér Bence
Published: March 2020

The Hungarian Runic script (or, according to another terminology, Szekler script), rarely used in the 10th–14th centuries, had got some popularity in the era of the Renaissance. There are a few examples, where the letters, originally devised for the Hungarian language, were combined with or used for Latin words. Thus the author of the Sepsikilyén wall graffito wrote X ʃcribʃit ◦ ← BNDK2 I[[L]]`  Ly´  ES, that is  Benedek Illyés scripsit; probably there is another hic fuit-graffito in Berekeresztúr from 1581, written partly in Runic script. The most prominent example is István Szamosközy’s Latin epigram from 1604, a pasquin against Emperor and King Rudolph, where Runic script was used as kind of a cryptography, the author had to set several orthographic rules for the Latin language in Runes and partially accommodated the graphotactics to the Latin custom too.
Johannes Valentini Lucubrata opuscula poeticohistorica in unum collecta [Az éjjeli mécs világánál alkotott költői-történeti művecskéim egybegyűjtése] (1808) című kötetének őstörténeti vonatkozásai
Authors: Szörényi László
Published: March 2020

As a poet, the parish priest Johannes Valentini (Turčiansky Michal, 1756 – Kláštor pod Znievom, 1812) is very much tied to the other Neo-Latin priest-poets living in Hungary and the other countries of the Habsburg Empire by the tradition of laudation in occasional poetry, which flourished from the antiquity until the end of the 19th century and was a tool to praise or mourn religious superiors or secular patronising potentates. Valentini, however, is different from the other poets in his very extensive interest in prehistory. When he poeticises the history of the provostry of Thurocz, he engages in lengthy explanations which are far bigger in size than the poem itself, and are also supplemented with footnotes.From a viewpoint of history of science this approach is probably connected mostly to the research initiated by the Jesuit historian Georgius Papánek, but Valentini’s work – similarly to authors of all other nationalities of that time in the Kingdom of Hungary – of course contains mythical and legendary elements, to which he naturally utilizes the reports of antique Greek and Roman writers about Eastern-origin exotic peoples. The Nagykároly (Carei, Szatmár county)-based Ferdinandus Thomas, for example, derives the origin of Hungarians from Ethiops! But we can name examples from either Romanian or South Slav literatures.Valentini is of high significance, because in many ways he – with his poet colleagues, writing in Slovak or other language – clears the way for Orientalism, an important trend of European Romanticism.
Vergilius Provence-ban: Marcel Pagnol Bucolica-fordítása II.
Authors: Pataki Elvira
Published: March 2020

In the long history of French translations of Vergilian Eclogues, the work of M. Pagnol (1895–1974) has a special place. The novelist, playwright and filmmaker (the first one of them elected to Académie Française) published his version of pastoral poems in 1958, two years after the highly artistic edition of P. Valéry. In a sociocultural approach, Pagnol’s translation is usually considered as a sophisticated tool of marketing used to remodel the image of the author. The popular and rich star of French theatre and cinema is not really accepted neither by academic literature nor by the movements of literary radicalism because of his regional features and his cheap sentimentalism. By translating Virgil in a quasi-academic way, by editing a text with a preface, commentary and notes, Pagnol would highlight his erudition and postulate a place for himself among the Classics. Nevertheless, his very funny and personal way to interpret Virgil, his cultural commentaries, and his ethical remarks based on the norms of modern urban society make the Latin poet accessible for a very wide audience. The current paper focuses on the aesthetic features of his work. Being born in Provence, passionate of the Mediterranean landscape and highly influenced by classical mythology, Pagnol appears to emphasize the Latin origins of his homeland, the cultural and ethnical continuity between the Antiquity and the 20th century, with a strong apparent wish to revive thousand-year-old traditions.
„ante alias venit in mentem […] Iohanna, serenissima Ierusalem et Sicilie regina” Egy ajánlás tervezett és tényleges címzettje – Johanna királynő és Andrea Acciaiuoli szerepe a De mulieribus clarisban
Authors: Molnár Annamária
Published: March 2020

Johanna királynő és Andrea Acciaiuoli szerepe a De mulieribus clarisban
„Nem vagyok sem Aeneas, sem Pál” – Dante túlvilágjárása és elődei I. Dante és Aeneas
Authors: Draskóczy Eszter
Published: March 2020

During his voyage through Hell and Purgatory led by Virgil, Dante the Pilgrim’s initial fear and pusillanimity (“I am not Aeneas”) turns into a strong but unspoken claim (I am a new Aeneas), and this transformation is marked by a number of references and rephrases of the Aeneid. The core of the renewal is the Christian message that follows the interpretation of allegorical commentaries. However, Dante draws on several other traditions in his artistic competition with his predecessors. Thus, he invokes Aeneas’ experiences, including his deeds, his map of the Underworld, his encounters, his major virtues, his determination, and his role model, Orpheus. The symbolic journey of the Commedia is longer than Virgil’s path as it eventually creates the Pilgrim’s identity, based on Biblical and apocalyptical tradition as well as medieval visionary literature.
Békét nem lelek… – Francesco Petrarca 104. szonettjének magyar fordításai
Authors: Képes Julianna
Published: March 2020

In this paper, I focus on Petrarch’s Sonnet 104 (Pace non trovo, et non ho da far guerra) in the respective Hungarian translations of György Sárközi, Győző Csorba and György Somlyó. I provide a comparative analysis between the original and each of the above mentioned translations, as well as between the three Hungarian translations of the same piece of poetry, pointing out the adequate and less adequate solutions. Based on the conclusions of this comparative analysis, I conclude by offering my own translation of Petrarch' Sonnet 104, which avoids some of the pitfalls of the earlier translations.
Da comunicação à qualidade em interpretação e tradução
Authors: Gile Daniel , Esqueda Marileide Dias , Freitas Flávio de Sousa
Published: March 2020

A tradução e interpretação profissionais agem sobre textos e discursos como um serviço de comunicação em contextos específicos de interação social. Ao se avaliar a qualidade desse serviço, os atores humanos envolvidos e suas intenções e outros parâmetros da situação de comunicação precisam ser levados em consideração. A variabilidade nas suas posições e na capacidade de aferir vários parâmetros de qualidade fazem da avaliação da qualidade um construto composto de um certo grau de subjetividade.
KNOWLEDGE ENABLED TECHNOLOGY SELECTION FOR SEWER CONDITION ASSESSMENT
Authors: Zeb Jehan
Published: March 2020

To improve the quality of life of communities, local government provides municipal services, including the sewer collection, effectively and efficiently employing asset management best practices. The condition assessment of assets (including the sewer collection system) is one of the core elements of implementing effective asset management across the utility organizations. Availability of sophisticated and complex condition assessment technologies, lack of common understanding about them and related high cost associated with sewer condition assessment requires the technologies and related knowledge to be explicitly defined in a neutral format-the ontology, to support the development of applications for technology selection. An ontology of condition assessment technologies for sewer network, CATS_Onto was developed following a seven-step approach at two levels of abstraction: meta-model and detailed ontology. This paper presents the development and verification of the meta-model. The proposed ontology will be used to develop a tool for the selection of the most appropriate technology for sewer condition assessment. The knowledge representation was verified while validation is underway.
LIFE CYCLE COST ANALYSIS OF ENERGY EFFICIENT SINGLE FAMILY RESIDENCE
Authors: Hajare Ayushi , Elwakil Emad
Published: March 2020

Residential and commercial buildings account for more than half of the electricity consumption in the United States. There are numerous practical solutions to make buildings more energy efficient and sustainable. Although it is well-established that green buildings are socially, environmentally, and economically beneficial, there is still a lack of green buildings in the residential sector. The installation and upfront costs for these houses are very high. This research aims to facilitate a broader understanding of the cost benefits of energy efficient and sustainable residences. The Life cycle cost analysis (LCCA) approach and energy simulation tools have been utilized and integrated for assessing the traditional single-family residence in the United States. A comparative study has been carried out including passive and net-zero energy through energy simulation software. This analysis will benefit academic researchers and industry practitioners to analyze and evaluate challenges and opportunities in energy efficient and sustainable residences.