bluuebunny/crossref_metadata_2025 huggingface dataset:
Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3
Authors: Maggi Lorenzo , Bello Luca , Bonanno Silvia , Govoni Alessandra , Caponnetto Claudia , Passamano Luigia , Grandis Marina , Trojsi Francesca , Cerri Federica , Ferraro Manfredi , Bozzoni Virginia , Caumo Luca , Piras Rachele , Tanel Raffaella , Saccani Elena , Meneri Megi , Vacchiano Veria , Ricci Giulia , Soraru' Gianni , D'Errico Eustachio , Tramacere Irene , Bortolani Sara , Pavesi Giovanni , Zanin Riccardo , Silvestrini Mauro , Politano Luisa , Schenone Angelo , Previtali Stefano Carlo , Berardinelli Angela , Turri Mara , Verriello Lorenzo , Coccia Michela , Mantegazza Renato , Liguori Rocco , Filosto Massimiliano , Marrosu Gianni , Siciliano Gabriele , Simone Isabella Laura , Mongini Tiziana , Comi Giacomo , Pegoraro Elena
Published: September 2020

Objective

To retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA).

Methods

Inclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6).

Results

We included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18–72). The Hammersmith Functional Rating Scale Expanded (HFMSE) in patients with SMA3 increased significantly from baseline to T6 (median change +1 point, p<0.0001), T10 (+2, p<0.0001) and T14 (+3, p<0.0001). HFMSE changes were independently significant in SMA3 sitter and walker subgroups. The Revised Upper Limb Module (RULM) in SMA3 significantly improved between T0 and T14 (median +0.5, p=0.012), with most of the benefit observed in sitters (+2, p=0.018). Conversely, patients with SMA2 had no significant changes of median HFMSE and RULM between T0 and the following time points, although a trend for improvement of RULM was observed in those with some residual baseline function. The rate of patients showing clinically meaningful improvements (as defined during clinical trials) increased from 53% to 69% from T6 to T14.

Conclusions

Our data provide further evidence of nusinersen safety and efficacy in adult SMA2 and SMA3, with the latter appearing to be cumulative over time. In patients with extremely advanced disease, effects on residual motor function are less clear.
Preclinical to clinical translation of cenerimod, a novel S1P1receptor modulator, in systemic lupus erythematosus
Authors: Strasser Daniel S , Froidevaux Sylvie , Sippel Virginie , Gerossier Estelle , Grieder Ursula , Pierlot Gabin M , Kieninger-Graefitsch Andrea , Vezzali Enrico , Stalder Anna K , Renault Bérengère , Ryge Jesper , Hart Aaron , Mentzel Ulrich , Groenen Peter M A , Keller Marcel P , Trendelenburg Marten , Martinic Marianne M , Murphy Mark J
Published: September 2020

Objectives:

SLE is an autoimmune disease characterised by aberrant lymphocyte activation and autoantibody production. This study provides an in-depth preclinical and clinical characterisation of the treatment effect of cenerimod, a sphingosine-1-phosphate receptor type 1 (S1P1) modulator, in SLE.

Methods:

Cenerimod effect on lymphocyte numbers, organ pathology, inflammation, and survival was evaluated in the MRL/lpr lupus mouse model. Lymphocytes from healthy subjects and patients with SLE were assessed for cenerimod-induced S1P1receptor internalisation. Lymphocyte subsets and inflammatory biomarkers were characterised in a 12-week phase 2 clinical study (NCT-02472795), where patients with SLE were treated with multiple doses of cenerimod or placebo.

Results:

In MRL/lpr mice treated with cenerimod, blood lymphocytes were reduced, leading to reduced immune infiltrates into tissue, and decreased tissue pathology, proteinuria, and inflammation, resulting in increased survival. Cenerimod was potent and efficacious in inducing S1P1receptor internalisation in lymphocytes in both healthy subjects and patients with SLE. In patients with SLE, 12-week cenerimod treatment resulted in a dose-dependent reduction of blood lymphocytes, antibody-secreting cells (ASC), and plasma IFN-α.

Conclusion:

Cenerimod significantly ameliorated systemic and organ-specific pathology and inflammation in a mouse model of SLE. In lymphocytes from patients with SLE, the S1P1receptor remained functional despite concomitant background medication. The preclinical lymphocyte reduction translated to patients with SLE and resulted in the normalisation of ASC and the reduction of IFN-associated biomarkers. The efficacy and safety of cenerimod is being further investigated in a long-term clinical study in patients with SLE (CARE; NCT-03742037).
Association between number and type of different ACPA fine specificities with lung abnormalities in early, untreated rheumatoid arthritis
Authors: Joshua Vijay , Hensvold Aase Haj , Reynisdottir Gudrun , Hansson Monica , Cornillet Martin , Nogueira Leonor , Serre Guy , Nyren Sven , Karimi Reza , Eklund Anders , Sköld Magnus , Grunewald Johan , Chatzidionysiou Katerina , Catrina Anca
Published: September 2020

Background

Rheumatoid arthritis (RA)-associated anticitrullinated protein/peptide antibodies (ACPA) might originate at mucosal sites such as the lungs. We aimed to examine the relationship between the ACPA repertoire and lung abnormalities on high-resolution CT (HRCT) in patients with earlyuntreated RA.

Methods

106 patients with newly diagnosed untreated RA were examined with HRCT of the lungs. Blood samples were analysed for presence of rheumatoid factor (RF) and ACPA using either a CCP2 detection kit or an immunochip containing 10 different citrullinated peptides. Association between HRCT findings and the antibody repertoire was assessed by logistic regression analysis.

Results

The number (%) of patients with HRCT abnormalities was 58 (54.7%) for parenchymal abnormalities and 68 (64.2%) for airway abnormalities. CCP2 IgG, RF IgA and antibodies against citrullinated fibrinogen were associated with the presence of parenchymal lung abnormalities. Interestingly, a high number of ACPA fine specificities gave a high risk of having parenchymal lung abnormalities at the time of RA diagnosis. No significant signals were identified between ACPA specificities and risk for airway abnormalities.

Conclusions

The presence of RF and ACPAs (especially against citrullinated fibrinogen peptides) as well as high number of ACPAs fine specificities are associated with parenchymal lung abnormalities in patients with early, untreated RA. This provides further support for an important pathogenic link between the lung and systemic autoimmunity, contributing to RA development.
Vertebral fracture risk in glucocorticoid-induced osteoporosis: the role of hypogonadism and corticosteroid boluses
Authors: Florez Helena , Hernández-Rodríguez Jose , Carrasco Josep Lluis , Prieto-González Sergio , Muxi Africa , Filella Xavier , Ruiz-Gaspà Silvia , Gómez-Puerta José A , Cid Maria , Espinosa Gerard , Monegal Ana , Guañabens Núria , Peris Pilar
Published: September 2020

Objective

The aim of this study was to identify the risk factors associated with fragility fracture (FF) development in glucocorticoid (GC)-treated patients.

Methods

127 patients (aged 62±18 years, 63% women) on GC-treatment (mean dose 14.5±14.1 mg/day and duration 47.7±69 months) were included. The clinical data collected included bone metabolism study (including gonadal axis), GC-treatment, disease activity, dual-energy X-ray absorptiometry analysis (evaluating densitometric osteoporosis (OP) and trabecular bone score (TBS) degraded microarchitecture values (DMA)), X-ray (assessing vertebral fractures (VF)), FRAX risk (GC-adjusted) and previous FF.

Results

17% of the patients had VF, 28% FF (VF and/or non-VF), 29% OP and 52% DMA. Patients with VF received more GC boluses (57.1% vs 29.5%, p=0.03), were older (68±13 vs 60±19 years, p=0.02), postmenopausal (100% vs 67%, p=0.02), had low testosterone levels (57% vs 11%, p=0.02), lower TBS values (1.119±0.03 vs 1.237±0.013, p<0.001) and higher FRAX risk (17.2±16 vs 9.3±7.6, p=0.003). Patients with FF showed higher accumulated GC doses (16.6±18.4 vs 11.1±12.9 g, p=0.046). On multivariate analysis, hypogonadism (OR 12.38; 95% CI 1.85 to >100, p=0.01) and having received GC boluses (OR 3.45; 95% CI 1.04 to 12.15, p=0.01) were the main factors related to VF. Hypogonadism (OR 7.03; 95% CI 1.47 to 38.37, p=0.01) and FRAX >20 (OR 7.08; 95% CI 1.28 to 53.71, p=0.02) were factors related to FF.

Conclusion

Hypogonadism is the principal risk factor for developing fractures in GC-treated men and women, whereas receiving GC boluses is a major factor for VF. These results indicate the importance of evaluating the gonadal axis in these patients.
SARS-CoV-2 seroprevalence and asymptomatic viral carriage in healthcare workers: a cross-sectional study
Authors: Shields Adrian , Faustini Sian E , Perez-Toledo Marisol , Jossi Sian , Aldera Erin , Allen Joel D , Al-Taei Saly , Backhouse Claire , Bosworth Andrew , Dunbar Lyndsey A , Ebanks Daniel , Emmanuel Beena , Garvey Mark , Gray Joanna , Kidd I Michael , McGinnell Golaleh , McLoughlin Dee E , Morley Gabriella , O'Neill Joanna , Papakonstantinou Danai , Pickles Oliver , Poxon Charlotte , Richter Megan , Walker Eloise M , Wanigasooriya Kasun , Watanabe Yasunori , Whalley Celina , Zielinska Agnieszka E , Crispin Max , Wraith David C , Beggs Andrew D , Cunningham Adam F , Drayson Mark T , Richter Alex G
Published: September 2020

Objective

To determine the rates of asymptomatic viral carriage and seroprevalence of SARS-CoV-2 antibodies in healthcare workers.

Design

A cross-sectional study of asymptomatic healthcare workers undertaken on 24/25 April 2020.

Setting

University Hospitals Birmingham NHS Foundation Trust (UHBFT), UK.

Participants

545 asymptomatic healthcare workers were recruited while at work. Participants were invited to participate via the UHBFT social media. Exclusion criteria included current symptoms consistent with COVID-19. No potential participants were excluded.

Intervention

Participants volunteered a nasopharyngeal swab and a venous blood sample that were tested for SARS-CoV-2 RNA and anti-SARS-CoV-2 spike glycoprotein antibodies, respectively. Results were interpreted in the context of prior illnesses and the hospital departments in which participants worked.

Main outcome measure

Proportion of participants demonstrating infection and positive SARS-CoV-2 serology.

Results

The point prevalence of SARS-CoV-2 viral carriage was 2.4% (n=13/545). The overall seroprevalence of SARS-CoV-2 antibodies was 24.4% (n=126/516). Participants who reported prior symptomatic illness had higher seroprevalence (37.5% vs 17.1%, χ2=21.1034, p<0.0001) and quantitatively greater antibody responses than those who had remained asymptomatic. Seroprevalence was greatest among those working in housekeeping (34.5%), acute medicine (33.3%) and general internal medicine (30.3%), with lower rates observed in participants working in intensive care (14.8%). BAME (Black, Asian and minority ethnic) ethnicity was associated with a significantly increased risk of seropositivity (OR: 1.92, 95% CI 1.14 to 3.23, p=0.01). Working on the intensive care unit was associated with a significantly lower risk of seropositivity compared with working in other areas of the hospital (OR: 0.28, 95% CI 0.09 to 0.78, p=0.02).

Conclusions and relevance

We identify differences in the occupational risk of exposure to SARS-CoV-2 between hospital departments and confirm asymptomatic seroconversion occurs in healthcare workers. Further investigation of these observations is required to inform future infection control and occupational health practices.
Progressive visual loss and severe retinal degeneration in a captive Kodiak bear (Ursus arctos mittendorfi)
Authors: Caruso Kelly A , Koch Seth , Reynolds Benjamin David , McCarthy Paul Massimo Giannoni , Whittaker Cameron J
Published: September 2020

A 27‐year‐old female Kodiak bear displayed signs of progressive visual loss over an 18‐year period. The bear was examined under general anaesthesia, where fixed mydriatic pupils, a diffusely hyper‐reflective retina with vascular attenuation was observed. An electroretinogram was performed bilaterally, revealing no electrical activity associated with either retina and confirming a diagnosis of severe bilateral retinal degeneration. The bear was euthanased eight months later due to a diagnosis of a metastasised hepatic neoplasm. Histopathology of the bear's eyes revealed marked outer layer retinal degeneration. The aetiology of this retinal degeneration could not be confirmed.
Laparoscopic iliopubic tract repair for pediatric inguinal hernia has very low recurrence: an Indian experience
Authors: Nayak Sunil Kumar , Parthasarathi Ramakrishnan , G H V Raghavendra Gupta , Rajapandian Subbaiah , Palanisamy Nalankilli Vaiyapurigoundar , Palanivelu Chinnusamy
Published: September 2020

Background

The aim of this study is to document results of laparoscopic iliopubic tract (IPT) repair for inguinal hernia in the pediatric age group.

Methods

Hospital records of 190 children who underwent IPT repair between January 2015 and January 2020 were analyzed retrospectively for demographic details, variations between clinical, radiological and laparoscopic diagnosis, associated pathologies, operative time, hospital stay, postoperative complications and follow-up. The internal ring was narrowed by approximating IPT to conjoint tendon using 3-0 polypropylene continuous or interrupted suture.

Results

In total, 238 IPT repairs were done under general anesthesia in 190 children aged between 1 and 17 years. 7.9% of children had phimosis, and three children had hydrocele. Three patients had undescended testis and another three IPT repairs were done in cases who presented with appendicitis. Contralateral patent processus vaginalis (CPPV) was detected at the time of laparoscopy in 18.3% of cases. Thus far, 166 children had been followed, and no recurrence was observed in any of these 96 of whom have completed more than 3 years after their surgery. However, two patients developed hernia on the contralateral side.

Conclusions

Laparoscopy is beneficial to pick up CPPV. Laparoscopic IPT repair for pediatric inguinal hernia is reproducible and safe with the least recurrence reported thus far. However, further follow-up is needed. Moreover, development of contralateral hernia needs to be investigated.
Soliton interaction in the Bose–Einstein condensate
Authors: Zuo Da-Wei , Xiang Xiao-Shuo
Published: September 2020

Wave function of the Bose–Einstein condensate satisfies the nonlinear evolution equation set, which is composed of the driven-dissipative Gross–Pitaevskii equations and rate equation (GPR). In this paper, a three coupled GPR equation is studied. By virtue of the bilinear method, multi-soliton solutions of this GPR equation are attained. Propagation and interaction of the solitons are discussed: propagation direction of the solitons are determined by the wave number; repellent and attractive two solitons are obtained by virtue of adjustment the wave numbers; interaction of the two solitons bound state are discussed; three solitons bound state are attained.
GAIT CHARACTERISTICS OF ELDERLY WOMEN IN OVERGROUND, ASCENT AND DESCENT WALKWAY CONDITIONS
Authors: KWON MOON-SEOK , KWON YU-RI , CHOI YOON-HYEOK , EOM GWANG-MOON , KO JUNGHYUK , KIM JI-WON
Published: September 2020

Gait assessment is important for identification of potential faller among the elderly populations. Slope walking is associated with fall risk factor and elderly women have higher fall rate compared with elderly men. Therefore, this study investigated gait characteristics of elderly women in overground and slope walkway conditions. Thirty healthy elderly women (15 younger-elderly women and 15 older-elderly women) walked along the linear walkway including three walking conditions (overground, ascent and descent conditions). Temporal gait variables and normalized peak vertical GRF (ground reaction force) variables were derived from commercial motion analysis software. Repeated-measures analysis of variance (ANOVA) was evaluated to compare mean differences of the three conditions and mean difference between younger and older elderly women. All gait characteristics were significantly different from the slope walking conditions ([Formula: see text]). Elderly women walked with longer loading response and mid stance phase during descent walking. Also, ascent walking induced a longer terminal stance phase. Interactions of age and walkway conditions were also significant in vertical GRF, where older-elderly women were greater than younger-elderly women in ascent walkway condition ([Formula: see text]) and in descent walkway condition ([Formula: see text]). These findings suggest that specific-walkway condition should be considered for fall prevention and clinical interventions in elderly women.
A comparison of epidemic prevention of COVID-19 between China and the US
Authors: Bian Qin
Published: September 2020

COVID-19 is becoming a large health and economic threat worldwide. Here, the epidemic statistics and prevention measures between China and the US are compared. It is noted that wearing masks at different stages of virus breakout, quarantine pattern, and policy executive strength may be the major factors causing the difference in effectiveness of the epidemic control.
Capturing the views of geoscientists on data sharing: a focus on the geotechnical community
Authors: Gilder Charlotte E. L. , Geach Martin , Vardanega Paul J. , Holcombe Elizabeth A. , Nowak Paul
Published: September 2020

The sharing of ground investigation (GI) data within the UK is commonly practised only in large infrastructure projects. A vast amount of GI data collected on routine projects is commonly not made publicly available which is arguably inefficient and potentially unsustainable. This paper captures the opinions of the geoscience community and the GI industry on data sharing to better understand current working practices and potential barriers to data sharing. The results of a survey carried out at the
Janet Watson Meeting 2018: A Data Explosion: The Impact of Big Data in Geoscience
held at the Geological Society of London are reported. This survey is compared with the results of interviews undertaken during the Dig to Share project, a collaborative project led by Atkins, British Geological Survey (BGS) and Morgan Sindall. The opinions and practices of geoscientists towards data sharing across a project life cycle are reviewed. Drivers of risk relating to geotechnical aspects of a project are directly linked to current data sharing practice.

Thematic collection:
This article is part of the Digitization and Digitalization in engineering geology and hydrogeology collection available at:
https://www.lyellcollection.org/cc/digitization-and-digitalization-in-engineering-geology-and-hydrogeology
Evidence of layered piezometry system within the Chalk aquifer in parts of SE England
Authors: Karapanos Ilias , Jaweesh Mahmoud , Yarker Daniel R. , Sage Robert C. , Marsili Alessandro , Powers Eleanor M.
Published: September 2020

The Chalk aquifer is often considered as a single, homogeneous, isotropic groundwater system in regional groundwater management studies, even though it has been subdivided into several different lithostratigraphic units. Low-permeability layers, including marl bands and hardgrounds, extend on a regional scale and define different layers within the Chalk. Four case studies in different locations of the Chalk aquifer of SE England are presented: (1) a multi-level observation borehole in the Upper Colne catchment in Hertfordshire; (2) different water levels in shallow and deep boreholes in the River Ver catchment; (3) artesian conditions and rises in the groundwater level during drilling in the Chiltern Hills; and (4) groundwater level separation in a public water supply borehole in Kent. The evidence clearly shows a layered system in the Chalk and vertical hydraulic discontinuity within the studied sequences. The current conceptual model of the Chalk aquifer should be enhanced to include this new understanding and to update the existing numerical groundwater models. This will, in turn, increase confidence in the current decision support tools for environmental sustainability and the management of water resources in the Chalk aquifer.
A Review of Peer Code Review in Higher Education
Authors: Indriasari Theresia Devi , Luxton-Reilly Andrew , Denny Paul
Published: September 2020

Peer review is the standard process within academia for maintaining publication quality, but it is also widely employed in other settings, such as education and industry, for improving work quality and for generating actionable feedback to content authors. For example, in the software industry peer review of program source code—or peer code review—is a key technique for detecting bugs and maintaining coding standards. In a programming education context, although peer code review offers potential benefits to both code reviewers and code authors, individuals are typically less experienced, which presents a number of challenges. Some of these challenges are similar to those reported in the educational literature on peer review in other academic disciplines, but reviewing code presents unique difficulties. Better understanding these challenges and the conditions under which code review can be taught and implemented successfully in computer science courses is of value to the computing education community. In this work, we conduct a systematic review of the literature on peer code review in higher education to examine instructor motivations for conducting peer code review activities, how such activities have been implemented in practice, and the primary benefits and difficulties that have been reported. We initially identified 187 potential studies and analyzed 51 empirical studies pertinent to our goals. We report the most commonly cited benefits (e.g., the development of programming-related skills) and barriers (e.g., low student engagement), and we identify a wide variety of tools that have been used to facilitate the peer code review process. While we argue that more empirical work is needed to validate currently reported results related to learning outcomes, there is also a clear need to address the challenges around student motivation, which we believe could be an important avenue for future research.
The university of DVD
Authors: Rushinek Avi , Rushinek Sara
Published: September 2020

Universities and training organizations increasingly use technology to record and distribute original material, bringing on a new class of technological and legal issues.
Thermodynamic/Electrochemical Description of High-Voltage Spinels for Lithium-Ion Batteries
Authors: Li Dajian , Zhang Weibin , Chang Keke , Yuan Yuan , Seifert Hans J.
Published: September 2020

High-voltage (HV) spinels obtained by partially substituting Mn with other elements in

LiMn

2

O

4

are promising cathode materials for lithium-ion batteries (LIBs) due to their superior energy capacities and recyclability. The improved performance of HV spinels comes from the appearance of multi voltage plateaus without phase transformation during lithiation/delithiation process. To optimize the doping elements is one significant routine to develop new cathode materials. However, it is difficult to investigate HV spinels with multi doping elements due to increased variables. For the first time, we investigate the typical HV spinel,

Li

Ni
,
Mn

2

O

4

using one single thermodynamic model with Compound Energy Formalism (CEF), i.e.,

Va
,

Li

+

1

Li

+

,

Ni

2
+

,

Ni

4
+

,

Mn

3
+

,

Mn

4
+

2

O

2
−

4

and described Ni substitution of Mn as well as lithiation/delithiation behaviours. Both the high voltage (around 4.7 V) and low voltage (around 4.1 V) plateaus of the Li-Ni-Mn-O spinel cathodes are predicted by correctly describing competition between

Mn

3
+

/

Mn

4
+

and

Ni

2
+

/

Ni

4
+

redox pairs. Meanwhile, we have successfully modelled the key property parameters including the voltage profile, energy density, stability, and cyclability. The presented design scheme is based on the superior cell performance compared to the widely studied

LiNi

0.5

Mn

1.5

O

4

,

which results in the slightly Li-rich HV spinel

Li

1
+
x

Ni

0.5

Mn

1.5
−
x

O

4

because of higher energy density and improved cyclability. The here adopted research strategy enables efficient design of the new-generation multi-doped HV spinel

Li

M
,
Mn

2

O

4

(M = Li, Al, Co, Cr, Cu, Mg, Fe, Ni, Zn, etc.).
Magnesium Zinc Oxide Nanostructure-Modified Multifunctional Sensors for Full-Scale Dynamic Monitoring of Pseudomonas aeruginosa Biofilm Formation
Authors: Li Guangyuan , Wu Yifan , Hong Yuzhi , Zhao Xilin , Reyes Pavel Ivanoff , Lu Yicheng
Published: September 2020

We demonstrate magnesium zinc oxide nanostructure (MZOnano) modified multifunctional devices for the full-scale dynamic monitoring of Pseudomonas aeruginosa (P. aeruginosa) biofilm formation: the dual-gate thin film transistor (DGTFT) as an electrical sensor for early stage detection and the quartz crystal microbalance (QCM) as an acoustic sensor for long-term monitoring. The sensing surfaces of both devices were modified with MZOnano to enhance their sensitivity and biocompatibility. P. aeruginosa bacteria were cultured in vitro on both sensing surfaces. The early stage detection is realized by sensing the charge transfer from cell membrane to the MZOnano during bacterial adhesion using the DGTFT biosensor while the monitoring of the long-term evolution is achieved through the sensing of mass loading and viscoelastic transition during biofilm development using the MZOnano QCM. The drain current of DGTFT starts to change at the beginning of the test and levels off after ∼6.5 h of bacterial inoculation, whereas the signals of MZOnano QCM become detectable after ∼5 h and then lasts for 24 h. The full-scale process of biofilm development covering from bacterial adhesion to maturation is thus dynamically monitored using this MZOnano modified multifunctional sensing technology.
Role of Air Pollution and rs10830963 Polymorphism on the Incidence of Type 2 Diabetes: Tehran Cardiometabolic Genetic Study
Authors: Jabbari Fatemeh , Mohseni Bandpei Anoushiravan , Daneshpour Maryam S. , Shahsavani Abbas , Hashemi Nazari Seyed Saeed , Faraji Sabokbar Hassanali , Momenan Amir abbas , Azizi Fereidoun
Published: September 2020

Diabetes mellitus (DM) is considered one of the leading health issues that are egregiously threatening human life throughout the world. Several epidemiological studies have examined the relationship of a particular matter<10 μm (PM10) exposure and with type 2 diabetes mellitus (T2DM) prevalence and incidence. Accordingly, the current study is a study investigating the independent influence of air pollution (AP) and rs10830963 on the incidence of T2DM. A total number of 2428 adults over 20 years of age participated in a prospective cohort (TCGS) during a 9-year follow-up phase. The concentration of AP was measured, and the obtained values were considered the mean level in three previous years since the exposure concentration took the people living in that location. The COX regression model was employed to determine the influence of AP and rs10830963 on the incidence of T2DM in adjustment with covariate factors. Among the 392 T2DM, 230 cases (58.7%) were female diabetics, and 162 (41.3%) were male diabetics. According to the multivariable-adjusted model, exposure to PM10 (per 10 μm/m3), associated with the risk of T2DM, although just a borderline (p=0.07) was found in the multivariable model (HR; 1.50, 95% CI; 1-2.32). The rs10830963 was directly associated with the incidence of diabetes, and the GG genotype increased the T2DM rate by 113% (more than two times) (HR; 2.134, 95% CI; 1.42-3.21, p≤0.001) and GC increased it by 65% (HR; 1.65, 95% CI; 1.24-2.21, p≤0.001). Long-term exposure to PM10 was associated with an increased risk of diabetes. Thus, it is suggested that the individuals with variant rs10830963 genotypes fall within a group susceptible to an increased risk of T2DM arising from AP.
An Application of Knowledge Engineering to Mathematics Curricula Organization and Formal Verification
Authors: Roanes-Lozano Eugenio , Martínez-Zarzuelo Angélica , Fernández-Díaz María José
Published: September 2020

The authors present a theoretical proposal for the organization of mathematical contents, more precisely to curricula development formalization and formal verification, inspired by knowledge engineering techniques. The situation addressed is the following: the starting point is a mathematical “official curriculum” (or part of it), not necessarily completely detailed. In our proposal, a group of experts would have to first build a detailed formulation of this curriculum (including the “prerequisite” relation between contents), which we will denominate “preprocessed official curriculum.” We detail how any “official curriculum development” could then be rigorously formalized and formally verified in a way inspired by rule-based expert system formal verification. We have defined the following terms: “contents soundness,” “contents completeness,” “relation soundness,” “relation completeness,” and “absence of cycles.” We believe that this is a completely new formalization within mathematics teaching theory that, once computer is implemented, would be very helpful. That would be the case, for instance, in countries where government sets the “official curricula” for Primary and Secondary Education and textbook contents have to be manually checked and approved by academic authorities: evaluators would “only” have to extract the textbook contents and set the “prerequisite” relation among them and let the computer do the rest.
Effect of sidt2 Gene on Cell Insulin Resistance and Its Molecular Mechanism
Authors: Xiong Qian-Ying , Xiong Chao-Qun , Wang Li-Zhuo , Gao Jia-Lin
Published: September 2020

Background. Sidt2 (SID1 transmembrane family, member 2) is a multiple transmembrane lysosomal membrane protein newly discovered in our previous study. In the previous study, we used gene targeting technique to make a mouse model of sidt2 gene knockout (sidt2-/-). It was found that sidt2-/- mice showed elevated fasting blood glucose and impaired glucose tolerance, showing a disorder of glucose metabolism, suggesting that sidt2 may be closely related to insulin resistance. We used 3T3-L1 adipocytes, C2-C12 myoblasts, and HEPA1-6 hepatoma cells as subjects to observe the effects of sidt2 on insulin-stimulated glucose uptake and the abovementioned insulin signal transduction pathways, and then to explore the effect of sidt2 on peripheral tissue insulin resistance and its possible molecular mechanism. Methods. (1) Lentiviruses with sidt2 gene knockout and puromycin resistance were constructed by Crispr/cas9 vector and transfected into 3T3-L1 adipocytes, C2-C12 myoblasts, and HEPA1-6 hepatoma cells to construct sidt2 knockout cell line model. (2) Glucose uptake of 3T3-L1 adipocytes, C2-C12 myoblasts, and HEPA1-6 hepatoma cells stimulated by insulin was detected by glucose detection kit, and the results were analyzed. (3) Sidt2 knockout group and control group of 3T3-L1 adipocytes, C2-C12 myoblast, and HEPA1-6 hepatoma cells were cultured according to the routine method. The total proteins of the above cells were extracted, and the expression of PAKT (thr308), PI3-K, and PIRS-1 (ser307) in the IRS-1 signaling pathway of the three groups was detected by western blot technique. Results. (1) The sidt2 elimination models of 3T3-L1 adipocytes, C2-C12 myoblasts, and HEPA1-6 hepatoma cells were successfully constructed. (2) It was found that the glucose uptake of cells in the sidt2 knockout group was lower than that in normal group under insulin stimulation through the detection of glucose concentration in the cell culture medium. (3) It was found that the expression of PAKT (thr308) and PI3-K protein decreased and the expression of PIRS-1 (ser307) protein increased in sidt2-/- group compared to the control group. Conclusions. sidt2 knockout can reduce glucose uptake in peripheral tissue under insulin stimulation, which may lead to peripheral tissue insulin resistance by affecting the IRS-1 signal pathway.
Towards Targeted Interventions in Low‐ and Middle‐Income Countries: Risk Profiles of People Who Inject Drugs in Haiphong (Vietnam)
Authors: Riondel Adeline , Huong Duong Thi , Michel Laurent , Peries Marianne , Oanh Khuat Thi Hai , Khue Pham Minh , Thanh Nham Thi Tuyet , Giang Hoang Thi , Vallo Roselyne , Cournil Amandine , Rapoud Delphine , Quillet Catherine , Laureillard Didier , Vinh Vu Hai , Moles Jean-Pierre , Feelemyer Jonathan , Hammett Ted , Jarlais Don Des , Nagot Nicolas
Published: September 2020

People who inject drugs (PWID) are a dominant risk group afflicted by blood‐borne viruses, mental health disorders, and social precariousness. Risk reduction interventions are administered to PWID regardless of their characteristics or specific risks. The objective of this cross‐sectional analysis was to empirically identify profiles of PWID regarding their drug use, risk behaviors, and mental health in order to tailor adapted interventions taking into account limited access to comprehensive care in middle‐income countries. PWID were recruited using respondent‐driven sampling. PWID with urine testing positive for heroin or methamphetamine and manifesting recent skin injection marks were enrolled. Classification of participants was based on drug use, injection, risky sexual behavior, and mental health data. This was subjected to multiple correspondence analysis followed by hierarchical cluster analysis combined with K‐means methodology. From October 2016 to January 2017, 1490 participants were recruited of which 1383 were eligible and enrolled. HCV prevalence was 70.5% and HIV prevalence 29.4%. The cluster analysis identified five distinct profiles: profile 1: recent injection practices and high alcohol consumption, profile 2: at‐risk injection and sexual behaviors with precarious situations, profile 3: no sexual activity and older age, profile 4: frequent injections with high methamphetamine use, and profile 5: stable partnerships and less frequent injections. Our study has identified profiles of PWID at particularly high risks, and they should thus be targeted for interventions tailored to their specific risks.
Effect of Blade Outlet Angle on Radial Force of Marine Magnetic Drive Pump
Authors: Zhang Hong-li , Kong Fan-yu , Zhu Ai-xia , Zhao Fei , Xu Zhen-fa
Published: September 2020

To research the effects of the blade outlet angle on the performance and the radial force of the marine pump, the unsteady numerical simulation of the four different models is carried out. The radial forces on the impeller and the blades are obtained under different flow rate conditions. The time and frequency domain characteristics of radial resultant force on the impeller and the blades are analyzed and those of the impeller torque are researched. The results show that the radial forces of the impeller and the blades increase with the increase of the blade outlet angle at the same flow rate. With the same blade outlet angle, the radial forces decrease with the increase of the flow rate. The roundness of radial force vector diagram becomes more obvious with the decrease of the blade outlet angle. The root mean square (RMS) of radial force on the blades is about 30% of that on the impeller. The main frequency of radial force on the impeller and the blades is the axial passing frequency (APF), and that of impeller torque is the blade passing frequency (BPF), and there are peaks at the blade frequency multiplier. At the same flow rate, the main frequency and maximum fluctuation amplitudes on the impeller and the blades increase with the increase of the blade outlet angle. Meanwhile, the impeller torque increases with the increase of the blade outlet angle. With the same blade outlet angle, the main frequency, maximum fluctuation amplitudes, and the impeller torque decrease with the increase of the flow rate. The amplitude difference decreases with the increase of the flow rate. The blade outlet angle has an obvious greater influence on the radial forces and fluctuation at the small flow rate. The vibration test shows that the vibration intensities of model 25 and model 35 are less than 2.5 mm/s, and the vibration intensity of model 25 is about 0.2 mm/s less than that of model 35.
Bipolar Disorder as Comorbidity with Sjögren’s Syndrome: What Can We Do?
Authors: Chebli Selima , Zgueb Yosra , Ouali Uta , Taleb Sana , Nacef Fethi
Published: September 2020

Neuropsychiatric manifestations in Sjögren’s syndrome are common and can occur not only during its course, but also at the onset of the disease. Depression and anxiety were the most frequently described symptoms. However, the association with bipolar disorder seems to be rare and not well documented. This case report presents a patient with bipolar disorder as comorbidity with Sjögren’s syndrome, suggesting that bipolar disorder could be associated with this autoimmune disease, which could lead to delaying diagnosis and treatment. A better analysis of the clinical background should be done by psychiatrists so to help early diagnosis and adapting prescription. Corticosteroids indicated in Sjögren’s syndrome should be prescribed with caution in bipolar disorder.
Selective Increment of Synovial Soluble TYRO3 Correlates with Disease Severity and Joint Inflammation in Patients with Rheumatoid Arthritis
Authors: Vullings Julia , Vago Juliana P. , Waterborg Claire E. J. , Thurlings Rogier M. , Koenders Marije I. , van Lent Peter L. E. M. , van der Kraan Peter M. , Amaral Flavio A. , van de Loo Fons A. J.
Published: September 2020

Objective. To investigate the role of TAM receptors in rheumatoid arthritis (RA) by determining synovial tissue TAM receptor expression, synovial fluid levels of soluble TAM receptors, and the relationship between soluble TAM receptors, joint inflammation and disease activity. Methods. TAM receptor expression was determined by immunohistochemistry on the synovium from RA and osteoarthritis (OA) patients. Soluble (s) Tyro3, sAxl, sMer, and their ligand Gas6 were measured by ELISA in the synovial fluid of RA (n=28) and OA (n=12) patients and cytokine levels by multiplex immunoassay in RA samples. Correlation analyses were performed among sTAM receptors with local cytokine levels; systemic disease parameters like erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anticyclic citrullinated peptide antibodies (ACPA); and disease activity scores (DAS28-ESR) in RA patients. Results. TAM receptors were expressed on different locations in the synovial tissue (lining, sublining, and blood vessels), and a similar expression pattern was observed in RA and OA patients. Synovial fluid sTyro3 and sMer were significantly enhanced in RA compared to OA patients, whereas no significant differences in sAxl and Gas6 levels were found. In RA samples, sTyro3 levels, but not sMer, correlated positively with proinflammatory local cytokines and the systemic factor erythrocyte sedimentation rate. Moreover, stratification analysis showed high sTyro3 levels positively correlated with higher DAS28-ESR and in RF and ACPA double positive RA patients. Conclusion. sTyro3 in the synovial fluid of RA patients correlates with local inflammatory molecules and systemic disease activity. These findings suggest that the reduced negative control of cell activation by TAM receptors due to their shedding in the synovial fluid, mainly sTyro3, favoring joint inflammation in RA patients.
Potent Activity of an Anti-ICAM1 Antibody–Drug Conjugate against Multiple Myeloma
Authors: Sherbenou Daniel W. , Su Yang , Behrens Christopher R. , Aftab Blake T. , Perez de Acha Olivia , Murnane Megan , Bearrows Shelby C. , Hann Byron C. , Wolf Jeffery L. , Martin Thomas G. , Liu Bin
Published: September 2020

Purpose:

New therapies have changed the outlook for patients with multiple myeloma, but novel agents are needed for patients who are refractory or relapsed on currently approved drug classes. Novel targets other than CD38 and BCMA are needed for new immunotherapy development, as resistance to daratumumab and emerging anti-BCMA approaches appears inevitable. One potential target of interest in myeloma is ICAM1. Naked anti-ICAM1 antibodies were active in preclinical models of myeloma and safe in patients, but showed limited clinical efficacy. Here, we sought to achieve improved targeting of multiple myeloma with an anti-ICAM1 antibody–drug conjugate (ADC).

Experimental Design:

Our anti-ICAM1 human mAb was conjugated to an auristatin derivative, and tested against multiple myeloma cell lines in vitro, orthotopic xenografts in vivo, and patient samples ex vivo. The expression of ICAM1 was also measured by quantitative flow cytometry in patients spanning from diagnosis to the daratumumab-refractory state.

Results:

The anti-ICAM1 ADC displayed potent anti-myeloma cytotoxicity in vitro and in vivo. In addition, we have verified that ICAM1 is highly expressed on myeloma cells and shown that its expression is further accentuated by the presence of bone marrow microenvironmental factors. In primary samples, ICAM1 is differentially overexpressed on multiple myeloma cells compared with normal cells, including daratumumab-refractory patients with decreased CD38. In addition, ICAM1-ADC showed selective cytotoxicity in multiple myeloma primary samples.

Conclusions:

We propose that anti-ICAM1 ADC should be further studied for toxicity, and if safe, tested for clinical efficacy in patients with relapsed or refractory multiple myeloma.
Health Insurance Coverage Mandates: Colorectal Cancer Screening in the Post-ACA Era
Authors: Preston Michael A. , Ross Levi , Chukmaitov Askar , Smith Sharla A. , Odlum Michelle L. , Dahman Bassam , Sheppard Vanessa B.
Published: September 2020

Building a culture of precision public health requires research that includes health delivery model with innovative systems, health policies, and programs that support this vision. Health insurance mandates are effective mechanisms that many state policymakers use to increase the utilization of preventive health services, such as colorectal cancer screening. This study estimated the effects of health insurance mandate variations on colorectal cancer screening post Affordable Care Act (ACA) era. The study analyzed secondary data from the Behavioral Risk Factor Surveillance System (BRFSS) and the NCI State Cancer Legislative Database (SCLD) from 1997 to 2014. BRFSS data were merged with SCLD data by state ID. The target population was U.S. adults, age 50 to 74, who lived in states where health insurance was mandated or nonmandated before and after the implementation of ACA. Using a difference-in-differences (DD) approach with a time-series analysis, we evaluated the effects of health insurance mandates on colorectal cancer screening status based on U.S. Preventive Services Task Force guidelines. The adjusted average marginal effects from the DD model indicate that health insurance mandates increased the probability of up-to-date screenings versus noncompliance by 2.8% points, suggesting that an estimated 2.37 million additional age-eligible persons would receive a screening with such health insurance mandates. Compliant participants' mean age was 65 years and 57% were women (n = 32,569). Our findings are robust for various model specifications. Health insurance mandates that lower out-of-pocket expenses constitute an effective approach to increase colorectal cancer screenings for the population, as a whole.

Prevention Relevance:

The value added includes future health care reforms that increase access to preventive services, such as CRC screening, are likely with lower out-of-pocket costs and will increase the number of people who are considered “up-to-date”. Such policies have been used historically to improve health outcomes, and they are currently being used as public health strategies to increase access to preventive health services in an effort to improve the nation's health.
Lactate-Modulated Immunosuppression of Myeloid-Derived Suppressor Cells Contributes to the Radioresistance of Pancreatic Cancer
Authors: Yang Xuguang , Lu Yun , Hang Junjie , Zhang Junfeng , Zhang Tiening , Huo Yanmiao , Liu Jun , Lai Songtao , Luo Dawei , Wang Liwei , Hua Rong , Lin Yuli
Published: September 2020

The mechanisms responsible for radioresistance in pancreatic cancer have yet to be elucidated, and the suppressive tumor immune microenvironment must be considered. We investigated whether the radiotherapy-augmented Warburg effect helped myeloid cells acquire an immunosuppressive phenotype, resulting in limited treatment efficacy of pancreatic ductal adenocarcinoma (PDAC). Radiotherapy enhanced the tumor-promoting activity of myeloid-derived suppressor cells (MDSC) in pancreatic cancer. Sustained increase in lactate secretion, resulting from the radiation-augmented Warburg effect, was responsible for the enhanced immunosuppressive phenotype of MDSCs after radiotherapy. Hypoxia-inducible factor-1α (HIF-1α) was essential for tumor cell metabolism and lactate-regulated activation of MDSCs via the G protein-coupled receptor 81 (GPR81)/mTOR/HIF-1α/STAT3 pathway. Blocking lactate production in tumor cells or deleting Hif-1α in MDSCs reverted antitumor T-cell responses and effectively inhibited tumor progression after radiotherapy in pancreatic cancer. Our investigation highlighted the importance of radiation-induced lactate in regulating the inhibitory immune microenvironment of PDAC. Targeting lactate derived from tumor cells and the HIF-1α signaling in MDSCs may hold distinct promise for clinical therapies to alleviate radioresistance in PDAC.
Sensory Stimulation for Nursing-Home Residents: Systematic Review and Meta-Analysis of Its Effects on Sleep Quality and Rest-Activity Rhythm in Dementia
Authors: Prins Angela Joanna , Scherder Erik J. Anton , van Straten Annemieke , Zwaagstra Yvonne , Milders Maarten Valentijn
Published: September 2020

Introduction: Disrupted sleep-wake cycles might be associated with an exacerbation of behavioural disturbances and accelerate disease progression in dementia. The effect of sensory stimulation for improving sleep quality is unclear. Methods: A systematic literature search was performed and all studies examining the effects of a sensory stimulation intervention (i.e. bright light, massage, acupuncture, animal-assisted interventions) on rest-activity rhythm (RAR) and/or nocturnal restlessness in nursing-home residents with dementia were included. Results: Sensory stimulation was shown to improve nocturnal behavioural restlessness as well as sleep duration and continuation, but the effect on the number of awakenings, RAR, and daytime sleep was negligible. Notable was the high heterogeneity between studies regarding treatments and patients’ characteristics and sleep parameters. Conclusion: Sleep quality and nocturnal restlessness in nursing-home residents with dementia may benefit from sensory stimulation. An environment with sensory stimulation may prevent or improve sleep disturbances in nursing homes, and thereby contribute to a better quality of life for their patients.