bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical stimulation to promote muscle and motor unit force and endurance after spinal cord injury
Authors: Gordon Tessa , Tyreman Neil
Published: February 2023

Fatigue is a common feature of paralysed skeletal muscle, hindering performance when subjected to functional electrical stimulation (ES) for movement. We asked whether (1) 20 Hz ES for 5% of each day (2.5 s on and 2.5 s off for 3 h) increases tibialis anterior and medial gastrocnemius muscle and motor unit (MU) endurance after paralysis by hemisection and deafferentation (HSDA), and (2) muscle length or loading affects their isometric contractile properties. The daily 5% ES increased muscle endurance, largely independent of muscle length or loading, but to a lesser extent than the daily 50% ES (2.5 s on and 2.5 s off for 24 h). The former was effective in counteracting the decline and slowing of muscle force promoted by the 50% ES. The altered muscle properties were confirmed at the MU level in final experiments once the properties had plateaued. Fast‐fatigable MUs were converted to fatigue‐intermediate and ‐resistant MUs that finally comprised ∼80% as compared to ∼10% of the total MU number in the daily 5% ES and the control normal groups, respectively. We conclude that the daily 5% ES regimen counteracts the fatigue of paralysed muscle without compromising contractile force, and thereby, is effective in conditioning muscle for effective movement.

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Key points

We asked whether 20 Hz electrical stimulation (ES) for 5% of each day (2.5 s on and 2.5 s off for 3 h; 5% ES) preserves medial gastrocnemius and tibialis anterior muscle and MU isometric contractile forces and increases their endurance after paralysis.

Daily 5% ES promoted increased muscle endurance irrespective of the muscle length or loading but to a lesser extent than daily 50% ES (20 Hz ES 2.5 s on and 2.5 s off for 24 h).

5% ES was effective in counteracting decline and slowing of muscle force that resulted from 50% ES.

Motor units (MUs) were converted from fast fatigable to fatigue intermediate and resistant MUs, comprising ∼80% as compared to ∼10% in the control normal groups.

We conclude that the 5% ES regimen counteracts the fatigue of paralysed muscle without compromising contractile force, and thereby is effective in conditioning the muscle for effective movement.
Novel regenerative drug, SPG302 promotes functional recovery of diaphragm muscle activity after cervical spinal cord injury
Authors: Fogarty Matthew J. , Zhan Wen‐Zhi , Simmon Vincent F. , Vanderklish Peter W. , Sarraf Stella T. , Sieck Gary C.
Published: February 2023

Spinal cord hemisection at C2 (C2SH), sparing the dorsal column is widely used to investigate the effects of reduced phrenic motor neuron (PhMN) activation on diaphragm muscle (DIAm) function, with reduced DIAm activity on the injured side during eupnoea. Following C2SH, recovery of DIAm EMG activity may occur spontaneously over subsequent days/weeks. Various strategies have been effective at improving the incidence and magnitude of DIAm recovery during eupnoea, but little is known about the effects of C2SH on transdiaphragmatic pressure (Pdi) during other ventilatory and non‐ventilatory behaviours. We employ SPG302, a novel type of pegylated benzothiazole derivative, to assess whether enhancing synaptogenesis (i.e., enhancing spared local connections) will improve the incidence and the magnitude of recovery of DIAm EMG activity and Pdi function 14 days post‐C2SH. In anaesthetised Sprague‐Dawley rats, DIAm EMG and Pdi were assessed during eupnoea, hypoxia/hypercapnia and airway occlusion prior to surgery (C2SH or sham), immediately post‐surgery and at 14 days post‐surgery. In C2SH rats, 14 days of DMSO (vehicle) or SPG302 treatments (i.p. injection) occurred. At the terminal experiment, maximum Pdi was evoked by bilateral phrenic nerve stimulation. We show that significant EMG and Pdi deficits are apparent in C2SH compared with sham rats immediately after surgery. In C2SH rats treated with SPG302, recovery of eupneic, hypoxia/hypercapnia and occlusion DIAm EMG was enhanced compared with vehicle rats after 14 days. Treatment with SPG302 also ameliorated Pdi deficits following C2SH. In summary, SPG302 is an exciting new therapy to explore for use in spinal cord injuries.

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Key points

Despite advances in our understanding of the effects of cervical hemisection (C2SH) on diaphragm muscle (DIAm) EMG activity, very little is understood about the impact of C2SH on the gamut of ventilatory and non‐ventilatory transdiaphragmatic pressures (Pdi).

Recovery of DIAm activity following C2SH is improved using a variety of approaches, but very few pharmaceuticals have been shown to be effective. One way of improving DIAm recovery is to enhance the amount of latent local spared connections onto phrenic motor neurons. A novel pegylated benzothiazole derivative enhances synaptogenesis in a variety of neurodegenerative conditions.

Here, using a novel therapeutic SPG302, we show that 14 days of treatment with SPG302 ameliorated DIAm EMG and Pdi deficits compared with vehicle controls.

Our results show that SPG302 is a compound with very promising potential for use in improving functional outcomes post‐spinal cord injury.
Predicting Nonlinear Modal Properties by Measuring Free Vibration Responses
Authors: Huang Shih-Chun , Chen Hao-Wen , Tien Meng-Hsuan
Published: February 2023

Identifying dynamical system models from measurements is a central challenge in the structural dynamics community. Nonlinear system identification, in particular, is a big challenge as there are many possible combinations of model structures, which requires expert knowledge to construct an appropriate model. Furthermore, traditional nonlinear system identification methods require a steady excitation input that is not always available in many practical applications. Recently, a technique referred to as the sparse identification of nonlinear dynamics (SINDy) algorithm was developed to discover mathematical models of general nonlinear systems. The SINDy method finds a generalized linear state-space model for an autonomous nonlinear system by analyzing the collected response data. In this work, the SINDy method is adapted and combined with the shooting method and the numerical continuation technique to form a system identification framework that can predict the nonlinear modal properties of mechanical oscillators. The proposed framework predicts the nonlinear normal modes (NNMs) of these systems by processing the noised data of the systems' free vibration response. In addition, the NNMs and the internal resonance of nonlinear systems at a high energy level can be captured using the proposed framework by processing the response data at a lower energy level. The proposed method is numerically demonstrated on a 2-degree-of-freedom mechanical oscillator. Furthermore, the effects of the measurement error and the excitation condition on NNM prediction are investigated. The NNM prediction framework presented in this paper is fairly general and is applicable to a variety of nonlinear systems.
Spin Direction of a Hemispherical Object
Authors: Wibowo Edy , Sutisna  , Ulya Naily , Rokhmat Mamat
Published: February 2023

When rotating a ball using a hand [Figs. 1(a) and (b)], the fingers that touch the ball’s outer surface will exert frictional forces on the ball. These frictional forces cause torques on the ball so that the ball spins in the same direction as the finger’s rotational direction. If the finger rotates clockwise, the ball’s rotational direction will also be clockwise and vice versa. When the ball is cut into half, it is rotated similarly to when spinning a full ball. Thus, we can easily guess that its direction of rotation will be the same as when circling a full ball. What if the ball is spun differently? The half ball is spun using one fingertip from the bottom center of the inside, as shown in Figs. 1(c) and (d). What is the direction of rotation of the half ball? Would it be the same as when the ball is rotated from the outside? It turns out that the spin direction of the half ball is the opposite of the finger’s spin direction. The same result was observed when using a pen or a stick to rotate the half ball from the center base [Fig. 1(d) and supplemental video. Finally, suppose we shift the finger’s tip to any location so that it will no longer be at the center of the bottom of the object. In that case, the half ball’s rotation direction is similar to the one of the finger or stick. Why does this happen? In this paper, the answer to this question is presented.
Simulating the Action Principle in Optics
Authors: Bari Refath
Published: February 2023

Light has a fascinating property: it always travels the path that takes the least time between any two points. This is the motivating property behind optical phenomena such as reflection and refraction. The unreasonable economic efficiency of light is captured by a single proposition: the principle of least action (PLA) in optics. Unlike reflection and refraction, which emerge from optimizing a one-dimensional function, the PLA emerges from optimizing an infinite-dimensional functional. The PLA can be difficult for students to comprehend, as the formulation of the Lagrangian is often left unexplained. To this end, this paper presents various simulations to demonstrate the action principle, including a numerical solution to a generalization of the brachistochrone problem to an arbitrary refractive profile. The interactive simulations discussed in the paper are available at Ref. 1.
Blind and visually impaired-accessible software and learning resources open a new window to the universe
Authors: Meredith Kate , Spuck Tim
Published: February 2023

In late 2016, Research Supporting Multisensory Engagement by Blind, Visually Impaired, and Sighted Students to Advance Integrated Learning of Astronomy and Computer Science [also known as Innovators Developing Accessible Tools for Astronomy (IDATA)] was funded by the National Science Foundation. IDATA explored the role of computational thinking in astronomy. Our approach partnered blind and visually impaired (BVI) and sighted middle and high school students and their teachers with undergraduate students, software engineers, astronomers, educators, and education researchers to, in part, design and develop a new BVI-accessible image analysis software tool called Afterglow Access (AgA). The goal of the IDATA project is to allow all users, regardless of visual acuity or level of astronomy knowledge, to collect and analyze their own astronomical images.
Manganese Efflux Achieved by MetA and MetB Affects Oxidative Stress Resistance and Iron Homeostasis in Riemerella anatipestifer
Authors: Guo Fang , Wang Mengying , Huang Mi , Jiang Yin , Gao Qun , Zhu Dekang , Wang Mingshu , Jia Renyong , Chen Shun , Zhao Xinxin , Yang Qiao , Wu Ying , Zhang Shaqiu , Huang Juan , Tian Bin , Ou Xumin , Mao Sai , Sun Di , Cheng Anchun , Liu Mafeng
Published: February 2023

Manganese is required for the function of many proteins in bacteria, but in excess, manganese can mediate toxicity. Therefore, the intracellular levels of manganese must be tightly controlled.
African Swine Fever Virus MGF505-7R Interacts with Interferon Regulatory Factor 9 to Evade the Type I Interferon Signaling Pathway and Promote Viral Replication
Authors: Huang Zhao , Cao Haoxuan , Zeng Fanliang , Lin Sizhan , Chen Jianglin , Luo Yi , You Jianyi , Kong Cuiying , Mai Zhanzhuo , Deng Jie , Guo Weiting , Chen Xiongnan , Wang Heng , Zhou Pei , Zhang Guihong , Gong Lang
Published: February 2023

ASF, caused by ASFV, is currently prevalent in Eurasia, with mortality rates reaching 100% in pigs. At present, there are no safe or effective vaccines against ASFV.
Draft Genome Sequences of Two Escherichia albertii Isolates Collected from Healthy Pets in Switzerland
Authors: Biggel Michael , Barmettler Karen , Treier Andrea , Muchaamba Francis , Stephan Roger
Published: February 2023

Here, we report the genome sequences of two
Escherichia albertii
isolates recovered from a healthy dog (KBD171i) and cat (KBK128i) in Switzerland in 2022. The genome sizes of KBK128i and KBD171i were 4.7 Mbp and 4.9 Mbp, respectively.
A Versatile Nanoluciferase Reporter Reveals Structural Properties Associated with a Highly Efficient, N-Terminal Legionella pneumophila Type IV Secretion Translocation Signal
Authors: Kang Yoon-Suk , Kirby James E.
Published: February 2023

Type IV secretion systems (T4SS) are used by Gram-negative pathogens to coopt host cell function. However, the translocation signals recognized by T4SS are not fully explained by primary amino acid sequence, suggesting yet-to-be-defined contributions of secondary and tertiary structure.
Diversity and Distribution of Harmful Algal Bloom Species from Seamount to Coastal Waters in the South China Sea
Authors: Huang Hailong , Xu Shuaishuai , Li Shuangqing , Wang Xinwei , Guo Kangli , Yan Rongman , Xie Wei , Yin Kedong , Hou Shengwei , Jiang Haibo
Published: February 2023

There are a number of seamounts under the water of the South China Sea (SCS). The seamounts might play a role in shaping the biodiversity of surrounding continental coastal waters.
Polysaccharide II Surface Anchoring, the Achilles’ Heel of Clostridioides difficile
Authors: Malet-Villemagne Jeanne , Yucheng Liang , Evanno Laurent , Denis-Quanquin Sandrine , Hugonnet Jean-Emmanuel , Arthur Michel , Janoir Claire , Candela Thomas
Published: February 2023

Cell wall glycopolymers (CWGPs) in Gram-positive bacteria have been reported to be involved in several bacterial processes. CWGP anchoring to peptidoglycan is important for growth and virulence.
Compositions and ages of Early Cretaceous volcanic and plutonic rocks in central Tibet: Insights into the magmatic and uplift response to slab breakoff
Authors: Wu Hao , Liu Fei , Liu Xi-Jun , Wu Yan-Wang , Li Cai , Yang Rui
Published: February 2023

We present new zircon U-Pb ages and Hf isotope compositions as well as whole-rock major- and trace-element geochemical and Sr-Nd isotopic data for silicic plutonic and volcanic rocks from the Duolong area of central Tibet. Combined with existing data, our new data indicate that these plutonic and volcanic rocks were formed in two stages ca. 120 Ma and ca. 110 Ma, respectively, in a postcollisional extensional setting that was triggered by slab breakoff. The similar geochemical compositions of granitoids and rhyolites, combined with their close spatial and temporal relationships, suggest that they were both derived from juvenile crustal material within a single magmatic system. We propose that the two inferred crustal melting events in the Duolong area were caused by two episodes of deep mantle activity triggered by the transition of the plate subduction angle from steep to shallow in response to the ascent of buoyant continental lithosphere during slab breakoff. Furthermore, rapid surface uplift during the late Early Cretaceous caused by slab breakoff made an important contribution to the formation of the proto–Tibetan Plateau. This study provides new insights into postcollisional tectonomagmatism and plateau uplift in central Tibet triggered by slab breakoff. We propose more generally that tectonic uplift during postcollisional processes (i.e., slab breakoff and lithospheric delamination) is a major contributor to plateau uplift in collision zones.
Appendiceal adenocarcinoma is associated with better prognosis than cecal adenocarcinoma: a population-based comparative survival study
Authors: Chen George , Chen Kay , Sahyoun Laura , Zaman Saif , Protiva Petr
Published: February 2023

Objective

Although appendiceal cancer remains a rare gastrointestinal malignancy compared with colorectal cancer, incidence rates of appendiceal cancer have increased in the last two decades. Appendiceal and cecal adenocarcinomas have distinct genomic profiles, but chemotherapy protocols for these malignancies are the same and survival outcomes between them have not been compared extensively. To this end, we conducted a comparative survival analysis of appendiceal and cecal adenocarcinomas.

Design

Using the Surveillance, Epidemiology and End Results (SEER) database, we identified individuals ≥30 years of age with appendiceal or cecal adenocarcinoma from 1975 to 2016. Demographic, clinical and county-level socioeconomic data were extracted using SEER*Stat software. Survival was compared by Mantel-Haenszel log-rank test, and survival curves were generated using the Kaplan-Meier method. Relative HRs for death in the 5-year period following diagnosis were calculated using multivariable Cox regression analysis, adjusted for all other covariates. The significance level was set at p<0.05 for two-tailed tests. Data were analysed using SAS V.9.4 and R software.

Results

We identified 6491 patients with appendiceal adenocarcinoma and 99 387 patients with cecal adenocarcinoma. Multivariable Cox regression analysis demonstrated significantly higher cancer-specific and overall survival in appendiceal adenocarcinoma compared with cecal adenocarcinoma. Male sex, older age, earlier year of diagnosis, black race, single marital status, non-Hispanic ethnicity, and non-mucinous histology were associated with increased mortality rates. In addition, counties with lower percentage of individuals below the poverty line and higher colorectal cancer screening rates had better survival.

Conclusion

This is the first study to show greater survival in appendiceal adenocarcinoma compared with cecal adenocarcinoma. We also highlighted novel associations of county-level socioeconomic factors with increased mortality in appendiceal adenocarcinoma. Future efforts to develop targeted molecular therapies and reduce socioeconomic barriers to diagnosis and treatment are warranted to improve survival.
Evaluating the implementation of community engagement guidelines (EVALUA GPS project): a study protocol
Authors: Cassetti Viola , López-Ruiz María Victoria , Domínguez Marta , Gallego-Royo Alba , García Ana María , Gea-Caballero Vicente , Nuñez Catalina , Paredes-Carbonell Joan Josep , Pérula-De Torres Luis Angel , Pola-Garcia Marina ,   EvaluAGPS Research Group, Benedé Azagra Carmen Belen
Published: February 2023

Introduction

The EVALUA GPS project aims to evaluate the impact of the implementation of the National Institute for Health Care and Excellence (NICE) guideline ‘Community engagement: improving health and well-being and reducing health inequalities’ adapted to the Spanish context.

Methods and analysis

Phase I: A tool will be designed to evaluate the impact of implementing the recommendations of the adapted NICE guideline. The tool will be developed through a review of the literature on implementation of public health guidelines between 2000 and 2021 and an expert’s panel consensus. Phase II: The developed tool will be implemented in 16 community-based programmes, acting as intervention sites, and 4 controls through a quasi-experimental pre–post study. Phase III: A final online web tool, based on all previously collected information, will be developed to support the implementation of the adapted NICE guidelines recommendations in other contexts and programmes.

Data collection and analysis

Data will be collected through surveys and semistructured interviews. Quantitative and qualitative data will be analysed to identify implementation scenarios, changes in community engagement approaches, and barriers and facilitators to the implementation of the recommendations. All this information will be further synthesised to develop the online tool.

Ethics and dissemination

The proposed research has been approved by the Clinical Research Ethics Committee of Aragon. Results will be presented at national and international conferences and published in peer-reviewed open access journals. The interactive online tool (phase III) will include examples of its application from the fieldwork.
Use of mental health services in the aftermath of COVID-19 waves: a retrospective study conducted in a French Psychiatric and Neurosciences University Hospital
Authors: Perozziello Anne , Sousa Daniel , Aubriot Béatrice , Dauriac-Le Masson Valérie
Published: February 2023

Objective

The COVID-19 pandemic and the restrictive measures taken to prevent its propagation had profound effects on mental health and well-being, especially in children and young adults (<25 years old). This study aimed to analyse the medium and long-term impact of the COVID-19 pandemic on the use of the mental health services, by age groups and gender.

Design

We conducted a retrospective study using the medical and administrative information system databases of patients, between 2019 and 2021.

Setting

This study was conducted in the Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences.

Outcome measures

We reported three indicators: the number of new patients attending outpatient clinics, the number of emergency department (ED) visits and the number of hospital admissions.

Methods

We considered the weekly number of each indicator, by age groups and by gender. We also collected the reasons of ED visits and hospital admissions. The 2020 and 2021 data were compared with the same period in 2019. The evolution of the indicators over the 3 years was analysed with interrupted time-series analysis.

Results

All three indicators showed a dramatic decrease during the first lockdown period (March 2020) especially for the youngest. In 2021, the activity resumed but without reaching its prepandemic level. Moreover, mental healthcare seeking was significantly lower since the beginning of the pandemic compared with the prepandemic period for all age groups, except for young women (<25 years old). Among them, there was a higher level of mental health services use in 2021, compared with 2019: +20% of new patients at the outpatient clinics, +39% of ED visits and+17% of hospital admissions.

Conclusions

The COVID-19 pandemic has had severe consequences on populations’ mental health, especially among young women, which seem to persist months after the end of restrictive measures.
Abstracts from international emergency medicine journals
Authors: Production EMJ
Published: February 2023

Editor’s note: EMJ has partnered with the journals of multiple international emergency medicine societies to share from each a highlighted research study, as selected by their editors. This edition will feature an abstract from each publication.
Quantitative p53 immunostaining aids in the detection of prevalent dysplasia
Authors: Neyaz Azfar , Rickelt Steffen , Yilmaz Omer H , Parrack Paige H , Lu Chenyue , Yilmaz Osman , Wu Elizabeth Y , Choi Won-Tak , Gala Manish , Ting David T , Odze Robert D , Patil Deepa T , Deshpande Vikram
Published: February 2023

Aims

The lack of accepted scoring criteria has precluded the use of p53 in routine practice. We evaluate the utility of automated quantitative p53 analysis in risk stratifying Barrett’s oesophagus (BE) patients using non-dysplastic BE (NDBE) biopsies in a multicentric cohort of BE progressor (P) and non-progressor (NP) patients.

Methods

NDBE biopsies prior to the diagnosis of advanced neoplasia from 75 BE-P, and index and last surveillance biopsies from 148 BE-NP were stained for p53, and scored digitally as 1+, 2+ and 3+. A secondary cohort of 30 BE-P was evaluated.

Results

Compared with BE-NP, BE-P was predominantly men (p=0.001), ≥55 years of age (p=0.008), with longer BE segments (71% vs 33%; p<0.001). The mean number of 3+p53 positive cells and 3+ positive glands were significantly more in BE-P versus BE-NP NDBE biopsies (175 vs 9.7, p<0.001; 9.8 vs 0.1; p<0.001, respectively). At a cut-off of ≥10 p53 (3+) positive cells, the sensitivity and specificity of the assay to identify BE-P were 39% and 93%. On multivariate analysis, scoring p53 in NDBE biopsies, age, gender and length of BE were significantly associated with neoplastic progression. 54% of patients classified as prevalent dysplasia showed an abnormal p53 immunohistochemical stain. These findings were validated in the secondary cohort.

Conclusions

Automated p53 analysis in NDBE biopsies serves as a promising tool for assessing BE neoplastic progression and risk stratification. Our study highlights the practical applicability of p53 assay to routine surveillance practice and its ability to detect prevalent dysplasia.
ANKRD22 is a potential novel target for reversing the immunosuppressive effects of PMN-MDSCs in ovarian cancer
Authors: Chen Huanhuan , Yang Keqing , Pang Lingxiao , Fei Jing , Zhu Yongliang , Zhou Jianwei
Published: February 2023

Background

Ovarian cancer is the deadliest type of malignant gynecological tumor. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are involved ovarian cancer and are closely related to adverse outcomes. However, the immunosuppressive mechanism of PMN-MDSCs remains elusive.

Methods

The types and numbers of ANKRD22-expressing cells were investigated by bioinformatics analysis and immunohistochemical staining.Ankrd22-/-C57BL/6 mice were constructed with CRISPR-Cas9 technology. Mouse PMN-MDSCs were obtained from bone marrow (BM)-derived CD11b+Ly6G+Ly6Clowcells sorted by fluorescence-activated cell sorting with treatment of GM-CSF and IL-6, and the immunosuppressive activity of PMN-MDSCs was evaluated by flow cytometry (FCM) and ELISA. The expression level of CCR2 and the exogenous glucose uptake capacity were determined by FCM. RT-qPCR was used to detectANKRD22expression in CD11b+HLA-DR-CD14-CD15+cells from human ovarian cancer tissues, and the correlations ofANKRD22expression with the clinical characteristics and prognosis of patients were evaluated by the χ2test.

Results

We identified a novel protein involved in regulating the immunosuppressive ability of PMN-MDSCs, ANKRD22.Ankrd22expression was high in mouse CD11b+Ly6G+Ly6Clowcells and could be significantly downregulated after exposure to a simulated microenvironmental stimulus. Knockout ofAnkrd22increased the expression level of CCR2 of CD11b+Ly6G+Ly6Clowcells and the immunosuppressive activity of PMN-MDSCs. BM-derived CD11b+Ly6G+Ly6Clowcells ofAnkrd22-/-mice significantly promoted the proliferation of ovarian cancer cells in tumor xenograft mouse models. Mechanistically, RNA sequencing showed thatWdfy1expression was obviously increased inAnkrd22-knockout BM-derived CD11b+Ly6G+Ly6Clowcells and that ectopic expression ofWdfy1increased the levels ofArg1,Inos,IdoandPdl1inAnkrd22+/+PMN-MDSCs derived from BM-derived CD11b+Ly6G+Ly6Clowcells. Surprisingly, an ANKRD22-activating candidate small-molecule compound attenuated the immunosuppressive activity ofAnkrd22+/+PMN-MDSCs. Finally, we found that lowANKRD22levels in CD11b+HLA-DR-CD14-CD15+cells derived from primary ovarian tissues were associated with a more advanced International Federation of Gynecology and Obstetrics stage, a higher recurrence rate, and a higher neutrophil-to-lymphocyte ratio.

Conclusions

These results suggest that ANKRD22 is a potential novel target for reversing the immunosuppressive effects of PMN-MDSCs.
Treg-selective IL-2 starvation synergizes with CD40 activation to sustain durable responses in lymphoma models
Authors: Stirm Kristin , Leary Peter , Wüst Daria , Stark Dominique , Joller Nicole , Karakus Ufuk , Boyman Onur , Tzankov Alexandar , Müller Anne
Published: February 2023

Background

Roughly half of all diffuse large B-cell lymphomas (DLBCLs) are infiltrated by large numbers of regulatory T-cells (Tregs). Although the presence of ‘effector’ Tregs in particular is associated with an inferior prognosis in patients on standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy, the role of this cell type during lymphoma initiation and progression is poorly understood.

Methods

Here, we use tissue microarrays containing prospectively collected DLBCL patient specimens, as well as data from publicly available cohorts to explore the mutational landscape of Treg-infiltrated DLBCL. We further take advantage of a model of MYC-driven lymphoma to mechanistically dissect the contribution of Tregs to lymphoma pathogenesis and to develop a strategy of Treg-selective interleukin-2 (IL-2) starvation to improve immune control of MYC-driven lymphoma.

Results

We find that all genetic DLBCL subtypes, except for one characterized by co-occurringMYD88/CD79mutations, are heavily infiltrated by Tregs. Spectral flow cytometry and scRNA-sequencing reveal the robust expression of functional and immunosuppressive markers on Tregs infiltrating MYC-driven lymphomas; notably, we find that intratumoral Tregs arise due to local conversion from naïve CD4+precursors on tumor contact. Treg ablation in Foxp3iDTRmice, or by antibody-mediated Treg-selective blockade of IL-2 signaling, strongly reduces the lymphoma burden. We identify lymphoma B-cells as a major source of IL-2, and show that the effects of Treg depletion are reversed by the simultaneous depletion of Foxp3-negative CD4+T-cells, but not CD8+T-cells or natural killer (NK) cells. The inhibition of ATP hydrolyzation and adenosine production by Tregs at least partly phenocopies the effects of Treg depletion. Treg depletion further synergizes with pro-apoptotic CD40 activation to sustain durable responses.

Conclusion

The combined data implicate Tregs as a potential therapeutic target in DLBCL, especially in combination with other immunotherapies.
Adjudicated myocarditis and multisystem illness trajectory in healthcare workers post-COVID-19
Authors: Sykes Robert , Morrow Andrew J , McConnachie Alex , Kamdar Anna , Bagot C , Bayes Hannah , Blyth Kevin G , Briscoe Michael , Bulluck Heeraj , Carrick David , Church Colin , Corcoran David , Delles C , Findlay Iain , Gibson Vivienne B , Gillespie Lynsey , Grieve Douglas , Barrientos Pauline Hall , Ho Antonia , Lang N N , Lowe David J , Lennie Vera , MacFarlane Peter , Mayne Kaithlin J , Mark Patrick , McIntosh Alasdair , McGeoch Ross , McGinley Christopher , Mckee Connor , Nordin Sabrina , Payne Alexander , Rankin Alastair , Robertson Keith E , Ryan Nicola , Roditi Giles H , Sattar Naveed , Stobo David B , Allwood-Spiers Sarah , Touyz Rhian , Veldtman Gruschen , Weeden Sarah , Watkins Stuart , Welsh Paul , Wereski Ryan , Mangion Kenneth , Berry Colin
Published: February 2023

Background

We investigated the associations of healthcare worker status with multisystem illness trajectory in hospitalised post-COVID-19 individuals.

Methods and results

One hundred and sixty-eight patients were evaluated 28–60 days after the last episode of hospital care. Thirty-six (21%) were healthcare workers. Compared with non-healthcare workers, healthcare workers were of similar age (51.3 (8.7) years vs 55.0 (12.4) years; p=0.09) more often women (26 (72%) vs 48 (38%); p<0.01) and had lower 10-year cardiovascular risk (%) (8.1 (7.9) vs 15.0 (11.5); p<0.01) and Coronavirus Clinical Characterisation Consortium in-hospital mortality risk (7.3 (10.2) vs 12.7 (9.8); p<0.01). Healthcare worker status associated with less acute inflammation (peak C reactive protein 48 mg/L (IQR: 14–165) vs 112 mg/L (52–181)), milder illness reflected by WHO clinical severity score distribution (p=0.04) and shorter duration of admission (4 days (IQR: 2–6) vs 6 days (3–12)).

In adjusted multivariate logistic regression analysis, healthcare worker status associated with a binary classification (probable/very likely vs not present/unlikely) of adjudicated myocarditis (OR: 2.99; 95% CI (1.01 to 8.89) by 28–60 days postdischarge).

After a mean (SD, range) duration of follow-up after hospital discharge of 450 (88) days (range 290, 627 days), fewer healthcare workers died or were rehospitalised (1 (3%) vs 22 (17%); p=0.038) and secondary care referrals for post-COVID-19 syndrome were common (42%) and similar to non-healthcare workers (38%; p=0.934).

Conclusion

Healthcare worker status was independently associated with the likelihood of adjudicated myocarditis, despite better antecedent health. Two in five healthcare workers had a secondary care referral for post-COVID-19 syndrome.

Trial registration number

NCT04403607.
Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection
Authors: Roca-Fernandez Adriana , Wamil Malgorzata , Telford Alison , Carapella Valentina , Borlotti Alessandra , Monteiro David , Thomaides-Brears Helena , Kelly Matt , Dennis Andrea , Banerjee Rajarshi , Robson Matthew , Brady Michael , Lip Gregory Y H , Bull Sacha , Heightman Melissa , Ntusi Ntobeko , Banerjee Amitava
Published: February 2023

Background

Long COVID is associated with multiple symptoms and impairment in multiple organs. Cross-sectional studies have reported cardiac impairment to varying degrees by varying methodologies. Using cardiac MR (CMR), we investigated a 12-month trajectory of abnormalities in Long COVID.

Objectives

To investigate cardiac abnormalities 1-year post-SARS-CoV-2 infection.

Methods

534 individuals with Long COVID underwent CMR (T1/T2 mapping, cardiac mass, volumes, function and strain) and multiorgan MRI at 6 months (IQR 4.3–7.3) since first post-COVID-19 symptoms. 330 were rescanned at 12.6 (IQR 11.4–14.2) months if abnormal baseline findings were reported. Symptoms, questionnaires and blood samples were collected at both time points. CMR abnormalities were defined as ≥1 of low left or right ventricular ejection fraction (LVEF), high left or right ventricular end diastolic volume, low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. Significant change over time was reported by comparison with 92 healthy controls.

Results

Technical success of multiorgan and CMR assessment in non-acute settings was 99.1% and 99.6% at baseline, and 98.3% and 98.8% at follow-up. Of individuals with Long COVID, 102/534 (19%) had CMR abnormalities at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing CMR abnormalities at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms or clinical outcomes. At baseline, low LVEF was associated with persistent CMR abnormality, abnormal GLS associated with low quality of life and abnormal T1 in at least three segments was associated with better clinical outcomes at 12 months.

Conclusion

CMR abnormalities (left entricular or right ventricular dysfunction/dilatation and/or abnormal T1mapping), occurred in one in five individuals with Long COVID at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers could not identify CMR abnormalities in Long COVID.

Trial registration number

NCT04369807.
Effect of COVID-19 pandemic restrictions on chlamydia and gonorrhoea notifications and testing in Queensland, Australia: an interrupted time series analysis
Authors: Dalmau Marguerite , Ware Robert , Field Emma , Sanguineti Emma , Si Damin , Lambert Stephen
Published: February 2023

Objective

To investigate trends in testing and notifications of chlamydia and gonorrhoea during the COVID-19 pandemic in Queensland, Australia.

Methods

Statewide disease notification and testing data between 1 January 2015 and 31 December 2021 were modelled using interrupted time series. A segmented regression model estimated the pre-pandemic trend and observed effect of the COVID-19 pandemic response on weekly chlamydia notifications, monthly gonorrhoea notifications and monthly testing figures. The intervention time point was 29 March 2020, when key COVID-19 public health restrictions were introduced.

Results

There were 158 064 chlamydia and 33 404 gonorrhoea notifications and 2 107 057 combined chlamydia and gonorrhoea tests across the 72-month study period. All three studied outcomes were increasing prior to the COVID-19 pandemic. Immediate declines were observed for all studied outcomes. Directly after COVID-19 restrictions were introduced, declines were observed for all chlamydia notifications (mean decrease 48.4 notifications/week, 95% CI −77.1 to –19.6), gonorrhoea notifications among males (mean decrease 39.1 notifications/month, 95% CI −73.9 to –4.3) and combined testing (mean decrease 4262 tests/month, 95% CI −6646 to –1877). The immediate decline was more pronounced among males for both conditions. By the end of the study period, only monthly gonorrhoea notifications showed a continuing decline (mean decrease 3.3 notifications/month, p<0.001).

Conclusion

There is a difference between the immediate and sustained impact of the COVID-19 pandemic on reported chlamydia and gonorrhoea notifications and testing in Queensland, Australia. This prompts considerations for disease surveillance and management in future pandemics. Possible explanations for our findings are an interruption or change to healthcare services during the pandemic, reduced or changed sexual practices or changed disease transmission patterns due to international travel restrictions. As pandemic priorities shift, STIs remain an important public health priority to be addressed.
Subaqueous landslides associated with historical road improvements in steep glaciated terrain, Loch Lomond, western Scotland
Authors: Finlayson Andrew , Nedumpallile-Vasu Nikhil , Carter Gareth , Dakin Nicola , Cooper Rhys
Published: February 2023

Shorelines in steep glaciated terrain are focal points for development and can provide important natural corridors for transport (e.g. road, rail). However, the steep subaqueous slopes at nearshore sites present challenging ground conditions, and only in recent decades has the acquisition of continuous high-resolution bathymetric datasets become available to inform investigations. This study investigates a site in Loch Lomond, Scotland, where a reported displacement of 15 000 m
3
of rock fill occurred prior to completion and stabilization of an embankment for the A82 road, during improvement work undertaken in the 1980s. We revisit the area using new multibeam swath bathymetry, shallow sub-bottom seismic data and geomorphological mapping, as well as borehole logs from the original ground investigation. The bathymetric and seismic data provide strong evidence for older subaqueous landslide activity at the site. The data indicate that embankment construction was also associated with occurrence of subaqueous landslides, incorporating a total volume of up to 95 000 m
3
. The research demonstrates the value of nearshore geophysical datasets in steep glaciated terrain, both for understanding geomorphological response to past shoreline modifications and as part of investigations where future developments (e.g. transport, energy infrastructure) are planned.
Building Knowledge through Action: Considerations for Machine Learning in the Workplace
Authors: Lindley Siân E. , Wilkins Denise J.
Published: February 2023

Innovations in machine learning are enabling organisational knowledge bases to be automatically generated from working people's activities. The potential for these to shift the ways in which knowledge is produced and shared raises questions about what types of knowledge might be inferred from working people's actions, how these can be used to support work, and what the broader ramifications of this might be. This article draws on findings from studies of (i) collaborative actions, and (ii) knowledge actions, to explore how these actions might (i) inform automatically generated knowledge bases, and (ii) be better supported through technological innovation. We triangulate findings to develop a framework of actions that are performed as part of everyday work, and use this to explore how mining those actions could result in knowledge being explicitly and implicitly contributed to a knowledge base. We draw on these possibilities to highlight implications and considerations for responsible design.
A Novel Review Helpfulness Measure Based on the User-Review-Item Paradigm
Authors: Pajola Luca , Chen Dongkai , Conti Mauro , Subrahmanian V.S.
Published: February 2023

Review platforms are viral online services where users share and read opinions about products (e.g., a smartphone) or experiences (e.g., a meal at a restaurant). Other users may be influenced by such opinions when deciding what to buy. The usability of review platforms is currently limited by the massive number of opinions on many products. Therefore, showing only the most
helpful
reviews for each product is in the best interest of both users and the platform (e.g., Amazon). The current state of the art is far from accurate in predicting how helpful a review is. First, most existing works lack compelling comparisons as many studies are conducted on datasets that are not publicly available. As a consequence, new studies are not always built on top of prior baselines. Second, most existing research focuses only on features derived from the review text, ignoring other fundamental aspects of the review platforms (e.g., the other reviews of a product, the order in which they were submitted).

In this article, we first carefully review the most relevant works in the area published during the last 20 years. We then propose the User-Review-Item (URI) paradigm, a novel abstraction for modeling the problem that moves the focus of the feature engineering from the review to the platform level. We empirically validate the URI paradigm on a dataset of products from six Amazon categories with 270 trained models: on average, classifiers gain +4% in F1-score when considering the whole review platform context. In our experiments, we further emphasize some problems with the helpfulness prediction task: (1) the users’ writing style changes over time (i.e., concept drift), (2) past models do not generalize well across different review categories, and (3) past methods to generate the ground truth produced unreliable helpfulness scores, affecting the model evaluation phase.
Exploring Myocardial Ischemia‐Reperfusion Injury Mechanism of Cinnamon by Network Pharmacology, Molecular Docking, and Experiment Validation
Authors: Xue Tao , Xue Yan , Fang Yangyue , Lu Chuanghong , Fu Yu , Lai Zefeng , Qin Xiaojun , Huang Feng , Zeng Zhiyu , Huang Jianping
Published: February 2023

Myocardial ischemia‐reperfusion injury (MIRI) is a common complication of acute myocardial infarction that seriously endangers human health. Cinnamon, a traditional Chinese medicine, has been used to counteract MIRI as it has been shown to possess anti‐inflammatory and antioxidant properties. To investigate the mechanisms of action of cinnamon in the treatment of MIRI, a deep learning‐based network pharmacology method was established to predict potential active compounds and targets. The results of the network pharmacology showed that oleic acid, palmitic acid, beta‐sitosterol, eugenol, taxifolin, and cinnamaldehyde were the main active compounds, and phosphatidylinositol‐3 kinase (PI3K)/protein kinase B (Akt), mitogen‐activated protein kinase (MAPK), interleukin (IL)‐7, and hypoxia‐inducible factor 1 (HIF‐1) are promising signaling pathways. Further molecular docking tests revealed that these active compounds and targets exhibited good binding abilities. Finally, experimental validation using a zebrafish model demonstrated that taxifolin, the active compound of cinnamon, has a potential protective effect against MIRI.
Enhanced Multiset Consensus Protocol Based on PBFT for Logistics Information Traceability
Authors: Zhang Linchao , Hang Lei , Kim Dohyeun
Published: February 2023

In the recent years, the global logistics industry has greatly driven the development of the world economy. At the same time, a large amount of data information is generated. Due to the frequent occurrence of logistics information leakage and forgery, it is necessary to find solutions that can accurately trace logistics information and ensure the security and authenticity of logistics information. The birth of blockchain technology has transformed the logistics industry from quantitative change to qualitative change. The technical characteristics of blockchain technology, such as distributed storage ideas, decentralization, immutability, and complex encryption consensus algorithm, endow it with a wide range of application prospects in the logistics industry. This paper proposes an enhanced multiset consensus algorithm based on PBFT (practical Byzantine fault tolerance) for logistics information traceability and storage on the logistics blockchain. The application of the proposed multi-set consensus algorithm in the topology structure composed of multiple sets can improve the consensus efficiency of logistics information in the blockchain. We improve consensus capability and transaction speed, avoid redundant consensus message packets occupying a large bandwidth, and efficiently process logistics information generated at any time. We ensure the traceability of logistics information and achieve efficient and accurate traceability, and the efficiency and security of the proposed algorithm are analyzed. This paper aims to solve the problems of traceability, trustworthiness, and efficient processing of blockchain applications in logistics information to operate the logistics network efficiently. This paper compares the proposed algorithm with the PBFT-related expansion algorithm regarding bandwidth occupation, delay, and throughput. The results show that the MPBFT consensus algorithm significantly improves the efficiency of the logistics blockchain network.
Hyaluronic Acid Dissolving Microneedles and Nonablative Fractional Laser for Infraorbital Wrinkles: A Prospective, Randomized, Split‐Face Study
Authors: Yang Yutong , Yan Jia , Shi Lei , Zhang Linglin , Liu Xiaojing , Long Fuquan , Wang Peiru , Wang Xiuli
Published: February 2023

Background. Recently, hyaluronic acid dissolving microneedles (HA‐DMNs) have been widely used in antiwrinkle research studies. However, the comparison of HA‐DMNs with nonablative fractional laser (NAFL), which is regarded as the gold standard in the treatment of facial wrinkles, is still lacking. Objective. The purpose was to compare the therapeutic effects and adverse effects of HA‐DMNs and NAFL on infraorbital wrinkles. Methods. A prospective, randomized, split‐face trial was performed with HA‐DMNs on one side and NAFL on the other. The wrinkle numbers, photo‐numeric scores, and VISIA assessment scores were compared at baseline and 2, 4, 8, and 12 weeks post‐treatment. Reflectance confocal microscopy (RCM) was used to monitor collagen fibers. Adverse effects and subjects’ satisfaction scores were evaluated using scales. Results. The final analysis included 28 patients. The wrinkle numbers and photo‐numeric scores decreased on both the HA‐DMNs side and the NAFL side in week‐2, 4, 8, and 12. The VISIA scores decreased on the HA‐DMNs side in week‐8 and on the NAFL side in week‐2. There were no significant differences in these indexes between the two sides. The RCM images demonstrated a similar increase in collagen density on the two sides. Burning, erythema, edema, and crust scores were higher on the NAFL side than on the HA‐DMNs side. There was no significant difference in the subjects’ satisfaction scores of the two sides. Conclusion. HA‐DMNs are effective treatment options for infraorbital rejuvenation. From the change of wrinkle numbers and scores, HA‐DMNs provided comparable efficacy as NAFL in an observation period of 12 weeks. Meanwhile, HA‐DMNs offered a more favorable adverse effect profile than NAFL therapy. Mild but persistent pain, erythema, and edema during the HA‐DMNs therapy are noteworthy and require improvement.