bluuebunny/crossref_metadata_2025 huggingface dataset:
Sunshine on KOLs: assessment of the nature, extent and evolution of financial ties between the leaders of professional medical associations and the pharmaceutical industry in France from 2014 to 2019: a retrospective study
Authors: Clinckemaillie Marie , Scanff Alexandre , Naudet Florian , Barbaroux Adriaan
Published: February 2022

Objective

To investigate the financial relationships between key opinion leader (KOL) or non-KOL physicians and pharmaceutical and device companies in France.

Design

Retrospective and descriptive study.

Setting

All doctors practising in France, with a focus on 548 KOLs (board members of the professional medical associations that published guidelines in 2018–2019, identified on the associations’ websites between 2018 and 2020). Ties were collected from the ‘Transparency in Healthcare’ database.

Main outcome measures

The number and the value of gifts from 2014 to 2019, and of remunerations and contractual agreements from 2017 to 2019.

Results

KOLs represented 0.24% of the total number of physicians in France. The total value of gifts declared in the French database for all physicians amounted to €818M (US$936M, £741M). At least one gift was declared for 83% of KOLs. KOLs’ gifts represented 0.68% of the total number of gifts to physicians and 1.5% of the total value of gifts, with a mean of €3700 per capita per year.

The total value of contractual agreements declared for all physicians amounted to €125M. Contractual agreements involving the KOLs represented 0.72% of the number of contractual agreements with physicians and 2.5% of the value of the agreements, with a mean of €1900 per capita per year.

A total of €156M in remunerations were declared for all physicians. KOL remunerations represented 2.3% of the number of physician remunerations and 4.4% of the total value of the remunerations paid to physicians, with a mean of €4100 per capita per year.

Almost all professional medical associations (99%) had at least one KOL in their board with a financial tie to the industry, but the amount varied widely among the associations.

Conclusion

Financial relationships between KOLs and the industry in France are extensive. KOLs have much more financial ties than non-KOL practitioners.
Associations between adverse childhood experiences, attitudes towards COVID-19 restrictions and vaccine hesitancy: a cross-sectional study
Authors: Bellis Mark A , Hughes Karen , Ford Kat , Madden Hannah C E , Glendinning Freya , Wood Sara
Published: February 2022

Objectives

Adverse childhood experiences (ACEs) can affect life-course health and well-being, including risk-taking behaviour and trust. This study explored associations between ACEs and trust in health information on COVID-19, attitudes towards and compliance with COVID-19 restrictions and vaccine hesitancy.

Design

National cross-sectional telephone survey using a sample of landline and mobile numbers stratified by Health Board, deprivation quintile and age group.

Setting

Households in Wales during national COVID-19 restrictions (December 2020 to March 2021).

Participants

2285 Welsh residents aged ≥18 years.

Measures

Nine ACEs; low trust in National Health Service (NHS) COVID-19 information; supporting removal of social distancing and mandatory face coverings; breaking COVID-19 restrictions; and vaccine hesitancy (rejection or uncertainty of vaccination).

Results

Increasing ACE counts were independently related to low trust in NHS COVID-19 information, feeling unfairly restricted by government and ending mandatory face coverings. High ACE counts (4+ vs 0 ACEs) were also associated with supporting removal of social distancing. Breaking COVID-19 restrictions increased with ACE count with likelihood doubling from no ACEs to 4+ ACEs. Vaccine hesitancy was threefold higher with 4+ ACEs (vs 0 ACEs) and higher in younger age groups. Thus, modelled estimates of vaccine hesitancy ranged from 3.42% with no ACEs, aged ≥70 years, to 38.06% with 4+ ACEs, aged 18–29 years.

Conclusions

ACEs are common across populations of many countries. Understanding how they impact trust in health advice and uptake of medical interventions could play a critical role in the continuing response to COVID-19 and controlling future pandemics. Individuals with ACEs suffer greater health risks throughout life and may also be excluded from interventions that reduce infection risks. While pandemic responses should consider how best to reach those suffering from ACEs, longer term, better compliance with public health advice is another reason to invest in safe and secure childhoods for all children.
Prevalence and associated factors of lower extremity musculoskeletal disorders among manufacturing workers: a cross-sectional study in China
Authors: Jin Xu , Dong Yidan , Wang Fujiang , Jiang Ping , Zhang Zhongbin , He Lihua , Forsman Mikael , Yang Liyun
Published: February 2022

Objective

To survey the prevalence of lower extremity musculoskeletal disorders (MSDs) among Chinese manufacturing workers, and to identify the associated factors.

Design

Observational study with cross-sectional design.

Setting

A self-administered questionnaire survey was conducted in four manufacturing factories in China.

Participants

7908 manufacturing workers were included in this study after excluding non-conforming personnel.

Outcome measures

Individual and work-related information, and MSDs in the whole leg and knee region were measured by the anonymous self-administered questionnaire. Individual and work-related factors associated with MSDs and their effects were identified through multivariate logistic regression.

Results

Of all respondents, 3241 (41.0%) reported having had lower extremity MSDs in the recent 12 months, and for the knees, ankles/feet and hips/thighs were 29.5%, 23.9% and 16.7%, respectively. After confounder-adjusted single-factor analysis, 22 variables (of 24) were significantly related to the disorders. Factors like always kneeling/squatting for long periods, always standing for long periods and often lifting in an uncomfortable position were shown to have higher risks, with ORs of 2.77 (95% CI: 2.33 to 3.30), 2.30 (1.96 to 2.69) and 2.25 (2.04 to 2.47). Comparable results were found on knee disorders. The final model included 15 variables of demography, biomechanics and work organisation. The following factors showed increased risks of lower extremity MSDs: being female, being older, longer working years, higher body mass index (BMI), keeping the same posture for a long time, awkward position, shift work and monotonous work. Whereas having enough breaks reduced the risk.

Conclusion

The prevalence of lower extremity MSDs among Chinese manufacturing workers is high. The most commonly affected body regions were the knees and ankles/feet. Multiple factors were found associated with lower extremity MSDs including age, BMI, work experience, work organisations, physical ergonomics exposures, etc.
Clinical outcomes of children with rheumatic heart disease
Authors: Zimmerman Meghan , Kitooleko Samalie , Okello Emmy , Ollberding Nicholas , Sinha Pranava , Mwambu Tom , Sable Craig , Beaton Andrea , Longenecker Chris , Lwabi Peter
Published: February 2022

Objective

To evaluate the long-term clinical outcomes of children with rheumatic heart disease (RHD) in Uganda, and determine characteristics that predict adverse outcomes.

Methods

This retrospective cohort study evaluated the risk of death in Ugandan children with clinical RHD from 2010 to 2018; enrolling children aged 5–18 years old from an existing registry. Demographic data and clinical data (baseline complications, RHD severity, cardiac interventions) were collected. The primary outcome was survival. Univariable and multivariable hazard ratios (HR) were obtained from Cox proportional hazards regression. Survival probabilities were developed using Kaplan-Meier curves; log-rank tests compared survival based on cardiac interventions, disease severity and time of enrolment.

Results

612 cases met inclusion criteria; median age 12.8 years (IQR 5.3), 37% were male. Thirty-one per cent (187 of 612) died during the study period; median time to death 7.8 months (IQR 18.3). In univariable analysis, older age (HR 1.26, 95% CI=1.0 to 1.58), presence of baseline complications (HR 2.06, 95% CI=1.53 to 2.78) and severe RHD (HR 5.21, 95% CI=2.15 to 12.65) were associated with mortality. Cardiac intervention was associated with a lower risk of mortality (HR 0.06, 95% CI=0.02 to 0.24). In multivariable models, baseline complications (HR 1.78, 95% CI=1.31 to 2.41), severe RHD (HR 4.58, 95% CI=1.87 to 11.23) and having an intervention (HR 0.05, 95% CI=0.01 to 0.21) remained statistically significant. Kaplan-Meier survival curves demonstrated >25% mortality in the first 30 months, with significant differences in mortality based on intervention status and severity of disease.

Conclusions

The mortality rate of children with clinical RHD in Uganda exceeds 30%, over an 8-year time frame, despite in-country access to cardiac interventions. Children at highest risk were those with cardiac complications at baseline and severe RHD.
Combined IL-2, agonistic CD3 and 4-1BB stimulation preserve clonotype hierarchy in propagated non-small cell lung cancer tumor-infiltrating lymphocytes
Authors: Shah Parin , Forget Marie-Andrée , Frank Meredith L , Jiang Peixin , Sakellariou-Thompson Donastas , Federico Lorenzo , Khairullah Roohussaba , Neutzler Chantal Alexia , Wistuba Ignacio , Chow Chi-Wan B , Long Yan , Fujimoto Junya , Lin Shiaw-Yih , Maitra Anirban , Negrao Marcelo V , Mitchell Kyle Gregory , Weissferdt Annikka , Vaporciyan Ara A , Cascone Tina , Roth Jack A , Zhang Jianjun , Sepesi Boris , Gibbons Don L , Heymach John V , Haymaker Cara L , McGrail Daniel J , Reuben Alexandre , Bernatchez Chantale
Published: February 2022

Background

Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) yielded clinical benefit in patients with checkpoint blockade immunotherapy-refractory non-small cell lung cancer (NSCLC) prompting a renewed interest in TIL-ACT. This preclinical study explores the feasibility of producing a NSCLC TIL product with sufficient numbers and enhanced attributes using an improved culture method.

Methods

TIL from resected NSCLC tumors were initially cultured using (1) the traditional method using interleukin (IL)-2 alone in 24-well plates (TIL 1.0) or (2) IL-2 in combination with agonistic antibodies against CD3 and 4-1BB (Urelumab) in a G-Rex flask (TIL 3.0). TIL subsequently underwent a rapid expansion protocol (REP) with anti-CD3. Before and after the REP, expanded TIL were phenotyped and the complementarity-determining region 3 β variable region of the T-cell receptor (TCR) was sequenced to assess the T-cell repertoire.

Results

TIL 3.0 robustly expanded NSCLC TIL while enriching for CD8+TIL in a shorter manufacturing time when compared with the traditional TIL 1.0 method, achieving a higher success rate and producing 5.3-fold more TIL per successful expansion. The higher proliferative capacity and CD8 content of TIL 3.0 was also observed after the REP. Both steps of expansion did not terminally differentiate/exhaust the TIL but a lesser differentiated population was observed after the first step. TIL initially expanded with the 3.0 method exhibited higher breadth of clonotypes than TIL 1.0 corresponding to a higher repertoire homology with the original tumor, including a higher proportion of the top 10 most prevalent clones from the tumor. TIL 3.0 also retained a higher proportion of putative tumor-specific TCR when compared with TIL 1.0. Numerical expansion of TIL in a REP was found to perturb the clonal hierarchy and lessen the proportion of putative tumor-specific TIL from the TIL 3.0 process.

Conclusions

We report the feasibility of robustly expanding a T-cell repertoire recapitulating the clonal hierarchy of the T cells in the NSCLC tumor, including a large number of putative tumor-specific TIL clones, using the TIL 3.0 methodology. If scaled up and employed as a sole expansion platform, the robustness and speed of TIL 3.0 may facilitate the testing of TIL-ACT approaches in NSCLC.
Delivery of CD47 blocker SIRPα-Fc by CAR-T cells enhances antitumor efficacy
Authors: Chen Huanpeng , Yang Yuying , Deng Yuqing , Wei Fengjiao , Zhao Qingyu , Liu Yongqi , Liu Zhonghua , Yu Bolan , Huang Zhaofeng
Published: February 2022

Background

Chimeric antigen receptor (CAR) T cell therapy has been successfully applied in treating lymphoma malignancies, but not in solid tumors. CD47 is highly expressed on tumor cells and its overexpression is believed to inhibit phagocytosis by macrophages and dendritic cells. Given the antitumor activity against preclinical model of CD47-blocking to induce the innate and adaptive immune system in the tumor microenvironment, here we developed a CAR-T cell secreting CD47 blocker signal regulatory protein α (SIRPα)-Fc fusion protein (Sirf CAR-T) to boost CAR-T cell therapeutic effect in solid tumor therapy.

Methods

Murine T cells were transduced to express a conventional anti-Trop2 CAR and Sirf CAR. The expression of SIRPα-Fc fusion protein in the supernatant of CAR-T cells and its effect on macrophage phagocytosis were tested in vitro. In vivo antitumor efficacy of CAR-T cells was evaluated in immunocompetent mice and analysis of the tumor microenvironment in the tumor-bearing mice was performed.

Results

We found that Sirf CAR-T cells dramatically decreased tumor burden and significantly prolonged survival in several syngeneic immunocompetent tumor models. Furthermore, we found that Sirf CAR-T cells induced more central memory T cells (TCM) and improved the persistence of CAR-T cells in tumor tissue, as well as decreased PD-1 expression on the CAR-T cell surface. In addition, we demonstrated that Sirf CAR-T cells could modulate the tumor microenvironment by decreasing myeloid-derived stem cells as well as increasing CD11c+ dendritic cells and M1-type macrophages in tumor tissue.

Conclusions

In summary, our findings indicate that CD47 blocker SIRPα-Fc enhances the antitumor efficacy of CAR-T cells and propose to block CD47/SIRPα signaling effect on CAR-T cells function, which could provide a new strategy for successful cancer immunotherapy by rationalizing combination of CD47 blocker and CAR-T cell therapy.
Parent artery-initiated and stent-mediated neointima formation in a rat saccular side wall model
Authors: Wanderer Stefan , Grüter Basil Erwin , Boillat Gwendoline , Sivanrupan Sivani , Rey Jeannine , Catalano Kristina , vonGunten Michael , Widmer Hans Rudolf , Andereggen Lukas , Marbacher Serge
Published: February 2022

Background

Unlike clipping that forms an immediate barrier of blood flow into intracranial aneurysms, endovascular treatments rely on thrombus organization and neointima formation. Therefore, a continuous endothelial cell layer is crucial to prevent blood flow in the former aneurysm. This study investigates the origin of endothelial cells in the neointima of endovascular treated aneurysms, specifically whether cells from the parent artery play a role in neointima formation.

Methods

In male rats, decellularized and vital side wall aneurysms were treated by coil (n=16) or stent embolization (n=15). The cell tracer CM-Dil dye was injected into the clamped aorta before aneurysm suture to mark initial endothelial cells in the parent artery and enable tracking of their proliferation during follow-up. Aneurysms were analyzed for growth, thrombus formation, and recurrence. Histological evaluation followed with cell counts for specific regions-of-interest.

Results

During follow-up, none of the 31 aneurysms ruptured. Macroscopic residual perfusion was observed in 12/16 rats after coiling and in 1/15 after stenting. Amounts of CM-Dil +cells in coiled versus stented decellularized aneurysms significantly decreased in the thrombus on day 7 (p=0.01) and neointima on day 21 (p=0.04). For vital aneurysms, the number of CM-Dil +cells in the neointima on day 21 showed no significant difference.

Conclusions

Healing patterns were worse in coil-treated than stent-treated aneurysms. Cell migration forming a neointima seemed mainly dependent on the adjacent vessel in decellularized aneurysms, but appeared buoyed by recruitment from aneurysm wall cells in vital aneurysms. Therefore, a cell-rich parent artery might be crucial.
Low-power CW laser-assisted synthesis of plasmonic aluminium nanoparticles using low duty cycle optical chopper
Authors: Swapna M.S. , Sankararaman S.
Published: February 2022

This paper reports continuous wave (CW) laser-assisted synthesis of plasmonic aluminium nanoparticles (ANPs) by drastically reducing the laser power density from the existing 105 W/cm2 to 9 W/cm2 using a specially designed ultralow duty cycle chopper. The aluminium target is subjected to laser irradiation by keeping it in a liquid medium maintained at a specific temperature. The effect of chopping frequencies (F), temperatures (T), and surfactant-glucose (C) on the formation of ANPs are investigated through field emission scanning electron microscopic and UV-visible spectroscopic analyses. The energy required for the ejection of ANPs from the target is obtained from the optical source, thermal source, and the molecular collision due to convection current. The purity of the nanoparticle is determined from energy dispersive spectroscopic analysis. The analysis reveals that ANPs of sizes in the range 20–50 nm are formed when F = 30 Hz, T = 60 °C, and C = 18 mg/cc, exhibiting excellent ageing stability. The photoluminescence spectrum, power spectrum, and CIE analyses for the excitations at 350 nm and 390 nm indicate the emission to be blue, suggesting that it is a suitable fluorescence material for UV-plasmonics.
Fission resonances observed in the $$^{237}$$Np(d,pf) reaction and the fission barrier topology of $$^{238}$$Np
Authors: Csige Lóránt , Csatlós Margit , Faestermann Thomas , Habs Dieter , Hunyadi Mátyás , Krasznahorkay Attila J. , Thirolf Peter G. , Tornyi Tamás G. , Wirth Hans-F.
Published: February 2022

The fission probability of $$^{238}$$

238

Np was measured as a function of the excitation energy in the energy range of E$$^* = 5.4 - 6.2$$

∗

=
5.4
-
6.2

MeV in order to search for transmission fission resonances. A radioactive $$^{237}$$

237

Np target was bombarded with deuterons of E$$_d$$

d

= 12 MeV, whereas the energy of the protons was analyzed with a superior resolution of $$\varDelta $$
Δ
E = 8 keV. The experiment was performed at the Tandem accelerator of the Maier-Leibnitz Laboratory in Garching employing the $$^{237}$$

237

Np(d,pf) reaction. A group of fission resonances has been observed at excitation energies between E$$^* = 5.5 - 5.8$$

∗

=
5.5
-
5.8

MeV, which could be ordered into three (superdeformed) rotational bands with a rotational parameter of $$\hbar ^2/2\varTheta = 3.507$$

ħ
2

/
2
Θ
=
3.507

keV, and identified as the first direct observation of transition states composing rotational bands in an odd-odd nucleus as they appear above the top of the outer fission barrier. Nuclear reaction code (talys1.95) calculations were also performed to extract the multi-humped fission barrier parameters of $$^{238}$$

238

Np by fitting them to the experimental data of the present (d,pf) and previous (n,f) experiments. The extracted barrier parameters also support the above interpretation of the observed resonances.
Naturally occurring underpressure – a global review
Authors: Birchall T. , Senger K. , Swarbrick Richard
Published: February 2022

Several mechanisms have been suggested as drivers of naturally occurring underpressure. However, the phenomenon is largely underrepresented in literature. Previous studies have focused on individual cases in North America, where challenges due to topography and defining hydrostatic gradients exist. More recent publications from underpressured basins have emerged from other parts of the world, where settings are arguably more favourable to studying the phenomenon. Based on a total of 29 underpressured locations, it is apparent that the magnitudes and depths of underpressure are similar throughout the world.

Pressures of up to 60 bar blow hydrostatic are common in sedimentary basins of North America, China, Russia, and Europe and typically occur at shallow depths (<2500 m). All occurrences of underpressure occur in areas that have been geologically recently uplifted and is predominantly confined to low permeability rocks. Although rarely tested, it appears that mudstone intervals are susceptible to developing underpressure. Given the shallowness, low permeability, and recent uplift of the cases, it seems that underpressure is typically a geologically short-lived phenomenon.

Thematic collection:
This article is part of the Geopressure collection available at:
https://www.lyellcollection.org/cc/geopressure
Saddle Point Optimization with Approximate Minimization Oracle and Its Application to Robust Berthing Control
Authors: Akimoto Youhei , Miyauchi Yoshiki , Maki Atsuo
Published: February 2022

We propose an approach to saddle point optimization relying only on oracles that solve minimization problems approximately. We analyze its convergence property on a strongly convex–concave problem and show its linear convergence toward the global min–max saddle point. Based on the convergence analysis, we develop a heuristic approach to adapt the learning rate. An implementation of the developed approach using the (1+1)-CMA-ES as the minimization oracle, namely, Adversarial-CMA-ES, is shown to outperform several existing approaches on test problems. Numerical evaluation confirms the tightness of the theoretical convergence rate bound as well as the efficiency of the learning rate adaptation mechanism. As an example of real-world problems, the suggested optimization method is applied to automatic berthing control problems under model uncertainties, showing its usefulness in obtaining solutions robust to uncertainty.
Anodic Dissolution Behavior of Al-Y Alloy in LiCl-KCl Eutectic and Its Passivation Inhibited Aided by LiF
Authors: Li Mei , Sun Zhongxuan , Han Wei , Liu Rugeng , Sun Yang , Zhang Meng
Published: February 2022

The anodic dissolution behaviors of solid Al-Y alloy were investigated in LiCl-KCl eutectic without and with LiF by electrochemical techniques. The passivation phenomenon was observed in LiCl-KCl eutectic and disappeared when LiF concentration higher than 3% by weight. The results of XRD and SEM-EDS indicated the composition of passive film was Al2O3. Meanwhile, the dissolution rate and current efficiency were also calculated using ICP-AES. Furthermore, the mechanism of LiF inhibiting passivation was explored and found the addition of LiF could increase alumina solubility. The kinetic properties were compared in LiCl-KCl and LiCl-KCl-LiF melts. The transfer resistance decreased obviously in LiCl-KCl-LiF melts.
Additive Manufacturing of Microcantilevers of Varying Stiffnesses for Sensing Applications
Authors: Foroughi Shervin , Habibi Mohsen , Packirisamy Muthukumaran
Published: February 2022

Fabrication of the microcantilevers using the traditional methods is time-consuming and costly. With the advancement of additive manufacturing methods, the fabrication of functional microcantilevers is possible. This work presents the fabrication of elastomeric microcantilevers using the SLA 3D printing technology. Different microcantilevers are fabricated. The mechanical characteristics of the fabricated cantilevers are identified by performing micromechanical tests. Results show that the cantilevers’ measured stiffnesses are comparable with those reported in the literature. The method explained in this work reveals the possibility of employing SLA 3D printing and soft elastomeric printing materials to fabricate microcantilevers.
Electroreduction of Si(NCO)4 for Electrodeposition of Si
Authors: Downes Nathanael , Vasquez Robert , Maldonado Stephen
Published: February 2022

The electrochemical reduction and concomitant suitability of tetraisocyanatosilane, Si(NCO)4, as a precursor for Si electrodeposition has been examined. At T = 25 °C, voltammetric data indicated that the electroreductive pathway of Si(NCO)4 paralleled the electroreduction of SiCl4, albeit with attenuated current densities. At T = 150 °C, the measured current density increased significantly due to coupled reaction likely involving an electropolymerization of the tetraisocyanato ligand. At either temperature, the electrochemical response of Si(NCO)4 did not strongly depend upon the identity of the anion in the supporting electrolyte. A combination of chronoamperometric, electron microscopy, and X-ray photoelectron spectroscopy data were used to study the morphology and composition of the electrodeposited Si films at room temperature. The composition and morphology of the as-electrodeposited films were consistent with the formation of amorphous Si when using solid n
+-Si electrodes, similar to what is observed during the electroreduction of SiCl4. Attempts to use Si(NCO)4 for Si crystal growth by the electrochemical liquid-liquid-solid (ec-LLS) process with a liquid e-GaIn electrode resulted in no appreciable crystalline Si product. Although Si(NCO)4 can be used for electrodeposition of amorphous Si onto solid electrodes at room temperature, more work is needed to identify conditions that would facilitate its use for ec-LLS.
Modeling Phase Transition in Battery Electrodes Using the Coupled Cahn-Hilliard – Phase Field Crystal Methods
Authors: Renuka Balakrishna Ananya , Chiang Yet-Ming , Carter W. Craig
Published: February 2022

Phase transitions in electrode materials are typically accompanied by lattice distortions and defect formations. These microscopic configurations affect an electrochemical cycle and influence the physical properties of electrode materials. Here, we explore the coupling between the lattice arrangements and Li-ion composition field in a representative FePO4 electrode particle. We develop and apply a 2D Cahn-Hilliard – phase-field crystal model that couples the Li-composition field with the underlying lattice symmetry of the FePO4 particle to describe phase transitions. We use this coupled model to explore lattice arrangements in uniformly lithiated/de-lithiated electrode particles, and to describe the lattice distortions across a diffuse phase boundary. Next, we model a Cahn-Hilliard type of diffusion for the Li-composition field and compute the accompanying structural evolution of atomic arrangements. In this theoretical study, we track the shape, size and orientation of grains during an electrochemical cycle. Furthermore, we report the electrode particles ability to reduce crystallographic imperfections through grain rotations and grain boundary migrations during an electrochemical cycle.
Strain-Reactivity Coupling Coefficients on Gold Thin Film in Electrocatalysis
Authors: Wu Xinyan , Graf Matthias , Weissmueller Joerg
Published: February 2022

A strong coupling effect between of mechanics on the electrochemical performance of potential electrocatalyst materials, affecting the surface strain is expected an effective way to enhance the final electrocatalytic efficiency.

However, the effect of strain on the reaction is still not well understood, especially with respect to diverse reaction and/or their pathways. A suitable measure to quantify this interaction are coupling coefficients, i.e. between the applied strain and the conversion current.

We present an approach to directly quantify this coupling between elastic surface strain to the canonical reaction of methanol oxidation based on the model system of planar gold (which is commonly regarded a catalytically inactive element). Two different strategies (Fig. 1) can provide access to the desired effect. We apply a controlled sine-circled strain with fixed frequency on an elastically deformable substrate carrying the gold thin film and adopt a lock-in technique to capture the modulated synchronous electric response during the whole methanol oxidation reaction process. Through this method, we can obtain the electrocapillary coupling coefficients as functions of the applied potentials, i.e. of each individual reaction step so that the method provides an access to the underlying mechanism (composed of steps of capacitive charging, O adsorption and methanol oxidation) which is not given by common cyclic voltammetry.

The obtained results show that strain significantly modifies the electrochemical surface properties as we thought, an obvious rise of the electrochemical sign in both potential-strain (ς) and current-potential coefficient (Λ) when methanol start to oxidize.

Figure 1
Controlling Ionomer Relaxation to Improve Fuel Cell Durability
Authors: Kim Yu Seung , Langlois David A. , Lee Albert Sung Soo , Purdy Geraldine M , Hjelm Rex , Yim Sung-Dae , Lei Chao , Xu Hui
Published: February 2022

One of the key issues to resolve for the wide spread commercialization of fuel cells in automobiles is their durability.1 It is known that when a fuel cell cathode undergoes electrical potential swings, between low and high cell voltages, fuel cell degradation increases. While most studies on fuel cell cathode degradation have examined catalyst particle dissolution/agglomeration2, the impact of the interaction between catalysts and polymer electrolytes should not be overlooked.

In this presentation, we will report our approach to forming a robust interface between the catalyst and the ionomer by controlling ionomer relaxation under fuel cell operating conditions. In the first part of the presentation, we will examine the non-equilibrium thermodynamics of Nafion in liquid media by using small angle neutron scattering analysis.3 The impact of the dispersing media on electrochemical reactions in fuel cell cathodes is explored by comparing the fuel cell beginning of life performance and the performance after potential cycling.4 In the second part, we will discuss a rejuvenation process which can control ionomer relaxation, improving fuel cell durability. The rejuvenation process was accomplished by the periodic exposure of a membrane electrode assembly to a dry-N2 gas stream, thus suppressing ionomer relaxation during potential cycling accelerated stress tests.5 We will demonstrate how this technique can effectively extend the lifetime of a fuel cell by over a factor of five. The impact of the rejuvenation process conditions will also be reported.

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K. Ahluwalia, S. Arisetty, J.-K. Peng, R. Subbaraman, X. Wang, N. Kariuki, D. J. Myers, R. Mukundan, R. Borup, and O. Polevaya, J. Electrochem. Soc., 161, F291 (2014)

S. Kim, C.F. Welch, R.P. Hjelm, N.H. Mack, A. Labouriau and E.B. Orler, Macromolecules, 48, 2161 (2015).

S. Kim, C.F. Welch, N.H. Mack, R.P. Hjelm, E.B. Orler, M.E. Hawley, K.S. Lee, S.-D. Yim and C.M. Johnston, Phys. Chem. Chem. Phys., 16, 5927 (2014).

S. Kim and D. Langlois, US Patent 9425461 (2016).
Rac1 regulates nucleus pulposus cell degeneration by activating the Wnt/β-catenin signaling pathway and promotes the progression of intervertebral disc degeneration
Authors: Yang Xiaoxu , Sun Yongjin , Li Xu , Zhang Wenzhi
Published: February 2022

Nucleus pulposus cell (NPC) dysfunction is considered as an important event related to intervertebral disc degeneration (IVDD). In the present study, tandem mass spectrometry (TMT) was used to detect total protein expression of nucleus pulposus (NP) in patients with IVDD and healthy controls. Bioinformatic analysis was performed to identify differentially expressed proteins that may be involved in the degeneration of NP. The results show that Rac1 may be a key protein involved in the degeneration of NP via Wnt/β-catenin pathway activation. We investigated the influence of Rac1 on IVDD degeneration and associated mechanisms. Rac1 expression increased in interleukin (IL)-1β-stimulated human NPCs, consistent with the results of TMT. The Rac1 inhibitor NSC23766 alleviated the degeneration of NPCs in vitro. Furthermore, Rac1 activated Wnt/β-catenin signaling, and the inhibition of this pathway significantly ameliorated the Rac1-mediated degenerative phenotype. NSC23766 exerted protective effects on IVDD in a puncture rat model. Taken together, these data suggest that Rac1 inhibition can delay NPC degeneration, probably through the regulation of the Wnt/β-catenin pathway. This study has the potential to advance understanding of the mechanism of occurrence of degenerative NP tissues and to provide novel strategies for slowing IVDD progression.
Manipulation of the miR-378a/mt-ATP6 regulatory axis rescues ATP synthase in the diabetic heart and offers a novel role for lncRNA Kcnq1ot1
Authors: Durr Andrya J. , Hathaway Quincy A. , Kunovac Amina , Taylor Andrew D. , Pinti Mark V. , Rizwan Saira , Shepherd Danielle L. , Cook Chris C. , Fink Garrett K. , Hollander John M.
Published: February 2022

Diabetes mellitus has been linked to an increase in mitochondrial microRNA-378a (miR-378a) content. Enhanced miR-378a content has been associated with a reduction in mitochondrial genome-encoded mt-ATP6 abundance, supporting the hypothesis that miR-378a inhibition may be a therapeutic option for maintaining ATP synthase functionality during diabetes mellitus. Evidence also suggests that long noncoding RNAs (lncRNAs), including lncRNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (Kcnq1ot1), participate in regulatory axes with microRNAs (miRs). Prediction analyses indicate that Kcnq1ot1 has the potential to bind miR-378a. This study aimed to determine if loss of miR-378a in a genetic mouse model could ameliorate cardiac dysfunction in type 2 diabetes mellitus (T2DM) and to ascertain whether Kcnq1ot1 interacts with miR-378a to impact ATP synthase functionality by preserving mt-ATP6 levels. MiR-378a was significantly higher in patients with T2DM and 25-wk-old Db/Db mouse mitochondria, whereas mt-ATP6 and Kcnq1ot1 levels were significantly reduced when compared with controls. Twenty-five-week-old miR-378a knockout Db/Db mice displayed preserved mt-ATP6 and ATP synthase protein content, ATP synthase activity, and preserved cardiac function, implicating miR-378a as a potential therapeutic target in T2DM. Assessments following overexpression of the 500-bp Kcnq1ot1 fragment in established mouse cardiomyocyte cell line (HL-1) cardiomyocytes overexpressing miR-378a revealed that Kcnq1ot1 may bind and significantly reduce miR-378a levels, and rescue mt-ATP6 and ATP synthase protein content. Together, these data suggest that Kcnq1ot1 and miR-378a may act as constituents in an axis that regulates mt-ATP6 content, and that manipulation of this axis may provide benefit to ATP synthase functionality in type 2 diabetic heart.
The therapeutic potential of exosomes derived from different cell sources in liver diseases
Authors: Pan Yun , Tan Wei-Feng , Yang Mu-Qing , Li Ji-Yu , Geller David A.
Published: February 2022

Exosomes are small nanovesicles with a size of approximately 40–120 nm that are secreted from cells. They are involved in the regulation of cell homeostasis and mediate intercellular communication. In addition, they carry proteins, nucleic acids, and lipids that regulate the biological activity of receptor cells. Recent studies have shown that exosomes perform important functions in liver diseases. This review will focus on liver diseases (drug-induced liver injury, hepatic ischemia-reperfusion injury, liver fibrosis, acute liver failure, and hepatocellular carcinoma) and summarize the therapeutic potential of exosomes from different cell sources in liver disease.
IL10 trains macrophage profibrotic function after lung injury
Authors: Bhattacharyya Aritra , Boostanpour Kaveh , Bouzidi Mohamed , Magee Liam , Chen Tian Y. , Wolters Rachel , Torre Paola , Pillai Satish K. , Bhattacharya Mallar
Published: February 2022

Cx3cr1+ monocyte-derived macrophages (moMacs) are recruited to tissues after injury and are known to have profibrotic effects, but the cell-cell interactions and specific pathways that regulate this polarization and function are incompletely understood. Here we investigate the role of moMac-derived Pdgfa in bleomycin-induced lung fibrosis in mice. Deletion of Pdgfa with Cx3cr1-CreERT2 decreased bleomycin-induced lung fibrosis. Among a panel of in vitro macrophage polarizing stimuli, robust induction of Pdgfa was noted with IL10 in both mouse and human moMacs. Likewise, analysis of single-cell data revealed high expression of the receptor IL10RA in moMacs from human fibrotic lungs. Studies with IL10-GFP mice revealed that IL10-expressing cells were increased after injury in mice and colocalized with moMacs. Notably, deletion of IL10ra with Csf1r-Cre: IL10ra fl/fl mice decreased both Pdgfa expression in moMacs and lung fibrosis. Taken together, these findings reveal a novel, IL10-dependent mechanism of macrophage polarization leading to fibroblast activation after injury.
Sex differences in TLR4 expression in SHR do not contribute to sex differences in blood pressure or the renal T cell profile
Authors: Belanger Kasey M. , Mohamed Riyaz , Webb R. Clinton , Sullivan Jennifer C.
Published: February 2022

Hypertension is a primary risk factor for the development of cardiovascular disease. Mechanisms controlling blood pressure (BP) in men and women are still being investigated; however, there is increasing evidence supporting a role for the innate immune system. Specifically, Toll-like receptors (TLRs), and TLR4 in particular, have been implicated in the development of hypertension in male spontaneously hypertensive rats (SHR). Despite established sex differences in BP control and inflammatory markers in hypertensive males and females, little is known regarding the role of TLR4 in hypertension in females. Our hypotheses were that male SHR have greater TLR4 expression compared with females, and that sex differences in TLR4 contribute to sex differences in BP and the T cell profile. To test these hypotheses, initial studies measured renal TLR4 protein expression in 13-wk-old male and female SHR. Additional SHR were implanted with telemetry devices and randomized to treatment with either IgG or TLR4 neutralizing antibodies. Untreated control male SHR have greater TLR4 protein expression in the kidney compared with females. However, treatment with TLR4 neutralizing antibody for 2 wk did not significantly alter BP in either male or female SHR. Interestingly, neutralization of TLR4 increased renal CD3+ T cells in female SHR, with no alteration in CD4+ T cells or CD8+ T cells in either sex. Taken together, our data indicate that although male SHR have greater renal TLR4 expression than females, TLR4 does not contribute to the higher BP and more proinflammatory renal T cell profile in males versus females.
Glycine receptor subunit-β-deficiency in a mouse model of spasticity results in attenuated physical performance, growth, and muscle strength
Authors: Rivares Cintia , Vignaud Alban , Noort Wendy , Koopmans Bastijn , Loos Maarten , Kalinichev Mikhail , Jaspers Richard T.
Published: February 2022

Spasticity is the most common neurological disorder associated with increased muscle contraction causing impaired movement and gait. The aim of this study was to characterize the physical performance, skeletal muscle function, and phenotype of mice with a hereditary spastic mutation (B6.Cg-Glrbspa/J). Motor function, gait, and physical activity of juvenile and adult spastic mice and the morphological, histological, and mechanical characteristics of their soleus and gastrocnemius medialis muscles were compared with those of their wild-type (WT) littermates. Spastic mice showed attenuated growth, impaired motor function, and low physical activity. Gait of spastic mice was characterized by a typical hopping pattern. Spastic mice showed lower muscle forces, which were related to the smaller physiological cross-sectional area of spastic muscles. The muscle-tendon complex length-force relationship of adult gastrocnemius medialis was shifted toward shorter lengths, which was explained by attenuated longitudinal tibia growth. Spastic gastrocnemius medialis was more fatigue resistant than WT gastrocnemius medialis. This was largely explained by a higher mitochondrial content in muscle fibers and relatively higher percentage of slow-type muscle fibers. Muscles of juvenile spastic mice showed similar differences compared with WT juvenile mice, but these were less pronounced than between adult mice. This study shows that in spastic mice, disturbed motor function and gait is likely to be the result of hyperactivity of skeletal muscle and impaired skeletal muscle growth, which progress with age.
A Case of Transvaginal Small Bowel Evisceration following Hysterectomy with Discussion of Emergency Department Diagnosis and Management
Authors: Apicella Matthew , Mayrink Maximiliano , Rajadhyaksha Chetan D. , Farcy David A.
Published: February 2022

Transvaginal small bowel evisceration is a rare surgical emergency that requires urgent surgery to prevent bowel necrosis, sepsis, and death. It was first reported in 1864 by Hyernaux with less than 100 cases reported since the original publication. The overall mortality rate is reported as 5.6 percent. We present the case of a 49-year-old woman who presented to the emergency department with a chief complaint of moderate abdominal pain and vaginal bleeding for 1 hour. The patient reported that she underwent a robotic-assisted laparoscopic hysterectomy 11 weeks prior for uterine fibroids. Visual examination revealed a loop of the small bowel coming from the superior aspect of her vagina. Literature reviews have noted a higher incidence of dehiscence following robotic-assisted total laparoscopic hysterectomy. It is important for the emergency physician to make the diagnosis, initiate prompt consultation with departments of obstetrics and gynecology and general surgery, and treat for potential infection.
P2Y2 Receptor Mediated Neuronal Regeneration and Angiogenesis to Affect Functional Recovery in Rats with Spinal Cord Injury
Authors: Cheng Ruidong , Zhu Genying , Ni Chengtao , Wang Rui , Sun Peng , Tian Liang , Zhang Li , Zhang Jie , Ye Xiangming , Luo Benyan
Published: February 2022

The aim of this study was to investigate the effect of the P2Y2 receptor (P2Y2R) signaling pathway on neuronal regeneration and angiogenesis during spinal cord injury (SCI). The rats were randomly divided into 3 groups, including the sham+dimethyl sulfoxide (DMSO), SCI+DMSO, and SCI+P2Y2R groups. The SCI animal models were constructed. A locomotor rating scale was used for behavioral assessments. The apoptosis of spinal cord tissues was detected by TUNEL staining. The expression levels of P2Y2R, GFAP, nestin, Tuj1, and CD34 were detected by immunofluorescence staining, and the expression levels of TNF-α, IL-1β, and IL-6 were detected by enzyme-linked immunosorbent assay. The locomotor score in the model group was significantly lower than the sham group. The expression of P2Y2R was increased after SCI. The expression levels of TNF-α, IL-1β, and IL-6 were increased remarkably in the SCI model group compared with the sham group. The P2Y2R inhibitor relieved neuronal inflammation after SCI. Compared with the sham group, the apoptotic rate of spinal cord tissue cells in the model group was significantly increased. The P2Y2R inhibitor reduced the apoptosis of the spinal cord tissue. The expressions of CD34, Tuj1, and nestin in the model group were decreased, while the expressions of GFAP and P2Y2R were increased. The P2Y2R inhibitor reversed their expression levels. The P2Y2R inhibitor could alleviate SCI by relieving the neuronal inflammation, inhibiting the spinal cord tissue apoptosis, and promoting neuronal differentiation and vascular proliferation after SCI. P2Y2R may serve as a target for the treatment of SCI.
Application of a FL Time Series Building Model in Mobile Network Interaction Anomaly Detection in the Internet of Things Environment
Authors: Chen Haotian , Lee Sukhoon , Jeong Dongwon
Published: February 2022

With the continuous development of the social economy, mobile network is becoming more and more popular. However, it should be noted that it is vulnerable to different security risks, so it is extremely important to detect abnormal behaviors in mobile network interaction. This paper mainly introduces how to detect the characteristic data of mobile Internet interaction behavior based on IOT FL time series component model, set the corresponding threshold to screen the abnormal data, and then use K-means++ clustering algorithm to obtain the abnormal set of multiple interactive data, and conduct intersection operation on all abnormal sets, so as to obtain the final abnormal detection object set. The simulation results show that the FL time series component model of the Internet of Things is effective and can support abnormal detection of mobile network interaction behavior.
Research on Drilling and Sealing Technology for Cross Bedding of Superthick Coal Seam
Authors: Li Yao-bin , Yue Cai-Hao , Guo Xin
Published: February 2022

Gas disasters have been affecting coal mine safety production. With the gradual deepening of coal resources development, whether gas extraction meets the standard is particularly important. In view of the low extraction efficiency, through theoretical and numerical simulation combined with field measurement, the upper and lower cross bedding drilling is studied. Through the simulation and comparison of gas pressure at different extraction time and the gas pressure changes when the spacing of boreholes is 8 m, 10 m, and 12 m, the results show that, under the designed parameters, when the pressure value at the middle of the two boreholes starts to be less than 0.74 Mpa, the standard extraction time of the upper and lower cross strata boreholes is 160 days, and the most suitable spacing of boreholes is 10 m. Combined with the actual situation of Baode Mine, the extraction effect of cross drilling and parallel drilling was compared. The research shows that the predrainage effect of cross drilling is obviously better than that of parallel drilling. Cross drilling improves the predrainage effect, prolongs the action time of gas extraction by drilling, and effectively eliminates the risk of coal seam outburst.
A Case of COVID-19-Associated Pediatric Multisystem Inflammatory Syndrome in Shock Managed by Cytokine Filtration
Authors: Lalwani Priyanka , Baskaran Subashini , Uribe Diego Arango , Ramaiah Anil , Saqib Aqdas , ElMesserey Mohammed , Fathi Emad M. , Tabata Yuichi , Fink Christoph , Pallavidino Marco
Published: February 2022

Multisystem inflammatory syndrome in children (MIS-C) after COVID-19 has been recognized as a complication arising due to cytokine storm. Several management strategies including intravenous immunoglobulin and immunomodulators have been reported. This case report highlights the use of a cytokine filter (oXiris®) in the management of MIS-C. Cytokine filters eliminate cytokines and reduce the demand for vasopressors in patients with other inflammatory conditions. A 7-year-old child with prolonged fever, vomiting, hypotension, elevated inflammatory mediators, and dilatation of coronary arteries on echocardiography was found to have positive SARS-CoV-2 IgG and PCR. He was diagnosed as MIS-C and was managed in the pediatric intensive care unit. He required ventilatory support, vasopressors, and continuous renal replacement therapy (CRRT) with a cytokine filter. He showed marked improvement within 24 hours of initiating CRRT. Cytokine filters may have a potential role in the management of severely ill children due to MIS-C. To our knowledge, this is the first report of successful use of the oXiris® membrane in MIS-C. However, further case series and controlled trials are needed to establish its use in this condition.