bluuebunny/crossref_metadata_2025 huggingface dataset:
No influence of threat uncertainty on fear generalization
Authors: Aslanidou Asimina , Andreatta Marta , Wong Alex H. K. , Wieser Matthias J.
Published: August 2023

Fear overgeneralization and perceived uncertainty about future outcomes have been suggested as risk factors for clinical anxiety. However, little is known regarding how they influence each other. In this study, we investigated whether different levels of threat uncertainty influence fear generalization. Three groups of healthy participants underwent a differential fear conditioning protocol followed by a generalization test. All groups learned to associate one female face (conditioned stimulus, CS+) with a female scream (unconditioned stimulus, US), whereas the other face (CS−) was not associated with the scream. In order to manipulate threat uncertainty, one group (low uncertainty, n = 26) received 80%, the second group (moderate uncertainty, n = 32) received 60%, and the third group (high uncertainty, n = 30) 40% CS‐US contingency. In the generalization test, all groups saw CS+ and CS− again along with four morphs resembling the CSs in steps of 20%. Subjective (expectancy, valence, and arousal ratings), psychophysiological (skin conductance response, SCR), and visuocortical (steady‐state visual evoked potentials, ssVEPs) indices of fear were registered. Participants expected the US according to their reinforcement schedules and the discriminative responses to CS+/CS− increased with more uncertainty in skin conductance. However, acquisition of conditioned fear was not evident in ssVEPs. During the generalization test, we found no effect of threat uncertainty in any of the measured variables, but the strength of generalization for threat expectancy ratings was positively correlated with dispositional intolerance of uncertainty. This study suggests that mere threat uncertainty does not modulate fear generalization.
Exploring the Limits of Empirical Correlations for the Design of Energy Systems With Complex Fluids: Liquid Sulfur Thermal Energy Storage as a Case Study
Authors: Oliver Madeleine C. , Shah Munjal , Martinek Janna , Nithyanandam Karthik , Ma Zhiwen , Martin Michael James
Published: August 2023

Sustainable energy technologies often use fluids with complex properties. As an example, sulfur is a promising fluid for use in thermal energy storage (TES) systems, with highly nonlinear thermophysical properties. The viscosity of liquid-phase sulfur varies by four orders of magnitude due to polymerization of sulfur rings between 400 K and 500 K, followed by depolymerization of long rigid chains, and a decrease in viscosity, as temperature increases. These properties may compromise the accuracy of long-established empirical correlations in the design of TES systems. This work uses computational fluid dynamics to compute steady-state free convection heat transfer coefficients of sulfur in concentric cylinders at temperatures between 400 K and 600 K. The results show that uneven distributions of high and low-viscosity sulfur in the system cause variations in flow patterns and highly nonlinear heat transfer coefficients as temperature gradients increase. As a result, existing empirical correlations for describing system performance become inaccurate. Comparisons of simulation results to predictions from well-established literature correlations show that deviations may surpass 50%. Nusselt versus Rayleigh number correlations for heat transfer are significantly affected by the loss of self-similarity. The analysis proves that existing correlations are not able to capture the complex properties of sulfur in this temperature range, suggesting that alternative modeling techniques are needed for the design and optimization of sulfur TES systems. These challenges are unlikely to be limited to sulfur as a working fluid or TES but will appear in a range of energy systems.
SARS-CoV-2 ORF8 accessory protein is a virulence factor
Authors: Bello-Perez M. , Hurtado-Tamayo J. , Mykytyn A. Z. , Lamers M. M. , Requena-Platek R. , Schipper D. , Muñoz-Santos D. , Ripoll-Gómez J. , Esteban A. , Sánchez-Cordón P. J. , Enjuanes L. , Haagmans B. L. , Sola I.
Published: August 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes six accessory proteins (3a, 6, 7a, 7b, 8, and 9b) for which limited information is available on their role in pathogenesis. We showed that the deletion of open reading frames (ORFs) 6, 7a, or 7b individually did not significantly impact viral pathogenicity in humanized K18-hACE2 transgenic mice. In contrast, the deletion of ORF8 partially attenuated SARS-CoV-2, resulting in reduced lung pathology and 40% less mortality, indicating that ORF8 is a critical determinant of SARS-CoV-2 pathogenesis. Attenuation of SARS-CoV-2-∆8 was not associated with a significant decrease in replication either in the lungs of mice or in organoid-derived human airway cells. An increase in the interferon signaling at early times post-infection (1 dpi) in the lungs of mice and a decrease in the pro-inflammatory and interferon response at late times post-infection, both in the lungs of mice (6 dpi) and in organoid-derived human airway cells [72 hours post-infection (hpi)], were observed. The early, but not prolonged, interferon response along with the lower inflammatory response could explain the partial attenuation of SARS-CoV-∆8. The presence of ORF8 in SARS-CoV-2 was associated with an increase in the number of macrophages in the lungs of mice. In addition, the supernatant of SARS-CoV-2-WT (wild-type)-infected organoid-derived cells enhanced the activation of macrophages as compared to SARS-CoV-2-∆8-infected cells. These results show that ORF8 is a virulence factor involved in inflammation that could be targeted in COVID-19 therapies.

IMPORTANCE

The relevance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF8 in the pathogenesis of COVID-19 is unclear. Virus natural isolates with deletions in ORF8 were associated with wild milder disease, suggesting that ORF8 might contribute to SARS-CoV-2 virulence. This manuscript shows that ORF8 is involved in inflammation and in the activation of macrophages in two experimental systems: humanized K18-hACE2 transgenic mice and organoid-derived human airway cells. These results identify ORF8 protein as a potential target for COVID-19 therapies.
Associations between human cytomegalovirus infection and type 2 diabetes mellitus: a systematic review and meta-analysis
Authors: Wang Xiaona , Chen Jun , Cao Zhichao , Yu Xuhui
Published: August 2023

Objective

Multiple studies have reported a potential contribution of human cytomegalovirus (HCMV) to the pathogenesis of type 1 diabetes and post-transplantation diabetes. However, the association between HCMV and type 2 diabetes mellitus (T2DM) remains unclear. In this paper, we employ the meta-analysis approach to investigate the potential correlation between HCMV infection and T2DM.

Method

The data of our study were collected from PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure and WAN FANG databases from inception to November 2022. Using the Review Manager V.5.4 software, the meta-analysis was performed.

Results

A total of 18 139 patients from 22 studies were included in our analysis. In the Asian subgroup, the patients with T2DM group had a significantly higher frequency of HCMV infection and older age compared with the healthy group. In the European, the frequency of HCMV infection in the T2DM was lower than the healthy group, although this difference was not statistically significant. After adjusting for demographic factors, the adjusted OR of T2DM for risk of by HCMV status was not found to be significant (adjusted OR=1.19, 95% CI=0.88 to 1.62, p>0.05). Additionally, T2DM with vasculopathy had a significantly higher rate of HCMV infection compared with those without vasculopathy (OR=1.87, 95% CI=1.24 to 2.83, p<0.05). Among T2DM with HCMV infection, there were significant increases in fasting blood glucose levels and the proportion of CD8+ T lymphocytes. Conversely, fasting blood insulin levels, the proportion of CD4+ T lymphocyte and the CD4+/CD8+ ratio were significantly decreased compared with the healthy group.

Conclusion

At present, the available evidence does not provide a clear understanding of whether there is a significant association between T2DM and HCMV infection. Additionally, T2DM with HCMV infection exhibited significantly worse blood glucose regulation and immune markers, as well as a higher frequency of vasculopathy.

PROSPERO registration number

CRD42022342066.
Safer medicines To reduce falls and refractures for OsteoPorosis (#STOP): a study protocol for a randomised controlled trial of medical specialist-initiated pharmacist-led medication management reviews in primary care
Authors: Moles Rebekah Jane , Perry Lin , Naylor Justine M , Center Jacqueline , Ebeling Peter , Duque Gustavo , Major Gabor , White Christopher , Yates Christopher , Jennings Matthew , Kotowicz Mark , Tran Thach , Bliuc Dana , Si Lei , Gibson Kathryn , Basger Benjamin Joseph , Bolton Patrick , Barnett Stephen , Hassett Geraldine , Kelly Ayano , Bazarnik Barbara , Ezz Wafaa , Luckie Kate , Carter Stephen Ross
Published: August 2023

Introduction

Minimal trauma fractures (MTFs) often occur in older patients with osteoporosis and may be precipitated by falls risk-increasing drugs. One category of falls risk-increasing drugs of concern are those with sedative/anticholinergic properties. Collaborative medication management services such as Australia’s Home Medicine Review (HMR) can reduce patients’ intake of sedative/anticholinergics and improve continuity of care. This paper describes a protocol for an randomised controlled trial to determine the efficacy of an HMR service for patients who have sustained MTF.

Method and analysis

Eligible participants are as follows: ≥65 years of age, using ≥5 medicines including at least one falls risk-increasing drug, who have sustained an MTF and under treatment in one of eight Osteoporosis Refracture Prevention clinics in Australia. Consenting participants will be randomised to control (standard care) or intervention groups. For the intervention group, medical specialists will refer to a pharmacist for HMR focused on reducing falls risk predominately through making recommendations to reduce falls risk medicines, and adherence to antiosteoporosis medicines. Twelve months from treatment allocation, comparisons between groups will be made. The main outcome measure is participants’ cumulative exposure to sedative and anticholinergics, using the Drug Burden Index. Secondary outcomes include medication adherence, emergency department visits, hospitalisations, falls and mortality. Economic evaluation will compare the intervention strategy with standard care.

Ethics and dissemination

Approval was obtained via the New South Wales Research Ethics and Governance Information System (approval number: 2021/ETH12003) with site-specific approvals granted through Human Research Ethics Committees for each research site. Study outcomes will be published in peer-reviewed journals. It will provide robust insight into effectiveness of a pharmacist-based intervention on medicine-related falls risk for patients with osteoporosis. We anticipate that this study will take 2 years to fully accrue including follow-up.

Trial registration number

ACTRN12622000261718.
Development of a subset of the international classification of functioning, disability and health as a basis for a questionnaire for community-dwelling older adults aged 75 and above in primary care: a consensus study
Authors: Rink Laura , Tomandl Johanna , Womser Sonja , Kühlein Thomas , Sebastião Maria
Published: August 2023

Objectives

Functioning of older adults needs to be adequately described before it can become the focus of care. The International Classification of Functioning, Disability and Health (ICF) provides a basis for describing functioning. As the ICF is too extensive for daily practice in primary care, there is a need for a reduced number of categories. The aim is to develop an ICF-subset for community-dwelling older adults aged 75 and above in primary care.

Design

The scientific basis for decision-making in our consensus study was laid by four preparatory studies, identifying potentially relevant ICF categories from four perspectives (research, patients’, experts’ and clinical perspective). The results of the preparatory phase were discussed by an international expert panel in a consensus study following the Nominal Group Technique (NGT).

Setting

An international 1-day online consensus conference.

Participants

International experts (n=7) participated in the consensus conference, meeting the following criteria: extensive expertise in the field of the ICF and/or caring for older adults, and being fluent in English.

Results

Each preparatory study yielded a different number of categories with some overlaps but also differences. The expert panel decided to: (1) restrict the subset to second-level categories and reduce the number of categories from the preparatory phase, (2) limit the subset to the component activities and participation and (3) weight the patients’ perspective as the most relevant one.

Conclusions

By using consensus techniques and the NGT, the process led to 51 second-level ICF categories to describe the functioning of community-dwelling older adults. The decisions made in the consensus conference emphasised the importance of considering the individual life situation from a more holistic perspective and addressing functioning as a focus of care. Next, the 51 categories will contribute to the development of an ICF-based questionnaire.
Psychosocial interventions for the prevention of self-harm repetition: protocol for a systematic review and network meta-analysis
Authors: Orri Massimiliano , Gifuni Anthony J , Ougrin Dennis , Boruff Jill , Cipriani Andrea , Furukawa Toshiaki A , Schaffer Dalia , Del Giovane Cinzia , Inja Ayla , Turecki Gustavo , Geoffroy Marie-Claude , Cortese Samuele
Published: August 2023

Introduction

Suicide is an important public health problem. Providing evidence-based psychosocial interventions to individuals presenting with self-harm is recognised as an important suicide prevention strategy. Therefore, it is crucial to understand which intervention is most effective in preventing self-harm repetition. We will evaluate the comparative efficacy of psychosocial interventions for the prevention of self-harm in adults.

Methods and analysis

We will perform a systematic review and network meta-analysis (NMA) of randomised controlled trials (RCTs) testing psychosocial interventions for the prevention of self-harm repetition. We will include RCTs in adults (mean age: 18 years or more) who presented with self-harm in the 6 months preceding enrolment in the trial. Interventions will be categorised according to their similarities and underpinning theoretical approaches (eg, cognitive behavioural therapy, case management). A health sciences librarian will update and adapt the search strategy from the most recent Cochrane pairwise systematic review on this topic. The searches will be performed in MEDLINE (Ovid), Embase (Ovid), PsycInfo (Ovid), CINAHL (EBSCO), Cochrane Central (Wiley), Cochrane Protocols (Wiley), LILACS and PSYNDEX from 1 July 2020 (Cochrane review last search date) to 1 September 2023. The primary efficacy outcome will be self-harm repetition. Secondary outcomes will include suicide mortality, suicidal ideation and depressive symptoms. Retention in treatment (ie, drop-outs rates) will be analysed as the main acceptability outcome. Two reviewers will independently assess the study eligibility and risk of bias (using RoB-2). An NMA will be performed to synthesise all direct and indirect comparisons. Ranked forest plots and Vitruvian plots will be used to represent graphically the results of the NMA. Credibility of network estimates will be evaluated using Confidence in NMA (CINeMA).

Ethics and dissemination

As this is the protocol for an aggregate-data level NMA, ethical approval will not be required. Results will be disseminated at national/international conferences and in peer-review journals.

Trial registration number

CRD42021273057.
Argipressin for prevention of blood loss during liver resection: a study protocol for a randomised, placebo-controlled, double-blinded trial (ARG-01)
Authors: Wisén Ellinor , Kvarnström Andreas , Sand-Bown Lena , Rizell Magnus , Pivodic Aldina , Ricksten Sven-Erik , Svennerholm Kristina
Published: August 2023

Introduction

Liver resection carries a high risk for extensive bleeding and need for blood transfusions, which is associated with significant negative impact on outcome. In malignant disease, the most common indication for surgery, it also includes increased risk for recurrence of cancer. Argipressin decreases liver and portal blood flow and may have the potential to reduce bleeding during liver surgery, although this has not been explored.

Method and analysis

ARG-01 is a prospective, randomised, placebo-controlled, double-blinded study on 248 patients undergoing liver resection at Sahlgrenska University Hospital, Sweden. Patients will be randomised to one of two parallel groups, infusion of argipressin or normal saline administered peroperatively. The primary endpoint is peroperative blood loss. Secondary outcomes include need for blood transfusion, perioperative variables, length of hospital stay, the inflammatory response, organ damage markers and complications at 30 days.

Ethics and dissemination

The study is enrolling patients since March 2022. The trial is approved by the Swedish Ethical Review Authority (Dnr 2021-03557) and the Swedish Medical Product Agency (Dnr 5.1-2021-90115). Results will be announced at scientific meetings and in international peer-reviewed journals.

Trial registration number

ClinicalTrials.gov,NCT05293041and EudraCT, 2021-001806-32
Contribution of contrast-enhanced ultrasound in the diagnosis of adnexal torsion (AGATA): protocol for a prospective comparative study
Authors: Pillot Rémi , Hossu Gabriela , Cherifi Aboubaker , Guillez Kévin , Morel Olivier , Beaumont Marine , Fijean Anne-Laure , Bertholdt Charline
Published: August 2023

Introduction

Adnexal torsion is a surgical emergency and its prognosis depends on the time elapsed prior to treatment. The diagnosis relies on pelvic ultrasound in which sensitivity remains low and may lead to misdiagnosis.

The primary objective is to evaluate the diagnostic performance of contrast-enhanced ultrasound for the diagnosis of adnexal torsion in women with suspected adnexal torsion. The secondary objectives are: (1) to describe the perfusion parameters of the ovaries by contrast-enhanced ultrasound, (2) to compare diagnostic performance of contrast ultrasound with bidimensional (2D) Doppler for the detection of adnexal torsion, (3) to describe the perfusion parameters of the ovarian as a function of the degree of adnexal torsion, (4) to compare perfusion parameters before and after ovarian detorsion and (5) to describe perfusion parameters of the ovarian by using MicroVascular Flow technique.

Methods and analysis

This is a monocentric, prospective comparative, non-randomised, open and interventional study. We hypothesise to include 30 women: 20 positive cases compared with 10 control cases. Women are informed and recruited in the emergency ward, over a period of 36 months.

The primary endpoint is the signal intensity measurement to assess sensitivity, specificity, positive and negative predictive values of contrast-enhanced ultrasound for detection of adnexal torsion in women with suspected adnexal torsion. The presence or absence of adnexal torsion is confirmed during the surgical intervention.

Ethics and dissemination

The study was approved by the French Ethics Committee, the CPP (Comité de Protection des Personnes) OUEST I on 3 July 2020 with reference number 2020T1-16. The results of this study will be published in a peer-reviewed journal and will be presented at relevant conferences.

Trial registration number

ClinicalTrials.gov registry (NCT04522219); EudraCT registry (2020-000993-27).
Exploring regional healthcare utilisation and quality of care for endometriosis in rural areas in Hesse, Germany: a mixed methods study protocol
Authors: Brauer Lara , Geraedts Max
Published: August 2023

Introduction

The need of a regional healthcare monitoring in order to evaluate quality and utilisation of health services in smaller scale is internationally and in Germany well established. Little is known about variation in healthcare in rural German areas, especially for women’s health. In particular, endometriosis is highly prevalent and known to be unsatisfactorily treated. Thus, this study aims to investigate utilisation and quality of care, the influence of structural determinants on quality and the patient’s experiences on endometriosis healthcare in rural Hesse.

Methods and analysis

We will use a mixed methods approach to ensure reliable mapping of the care situation for endometriosis patients in seven counties in Central and Eastern Hesse. First, retrospective secondary utilisation data and quality indicators will be used to describe possible regional variation in the treatment of endometriosis in the outpatient and inpatient sector. Second, we compare structural determinants of regions with quality of care. Third, we conduct qualitative, semistructured interviews with endometriosis patients on their perspective and experiences in those chosen rural regions. Data will then be analysed using descriptive statistics, small area variation analyses and multifactorial analyses of variance (ANOVAs). The interview will be interpreted using the experience-focused phenomenological approach.

Ethics and dissemination

The study has been approved by the ethics committee of Philipps-University Marburg. Utilisation data and structural determinants are anonymised and partly aggregated. The interview will use tokens for pseudonymisation to prevent the collected data from being assigned to an individual person. Also, informed consent will be obtained from patients.

The results of this study will be reported to the scientific community in peer-reviewed journals and at conferences. A summary of the key findings will be provided to the interviewed patients and theEndometriosis Association Germany.
Two-loop infrared renormalization with on-shell methods
Authors: Baratella Pietro , Maggio Sara , Stadlbauer Michael , Theil Tobias
Published: August 2023

Within the framework proposed by Caron-Huot and Wilhelm, we give a recipe for computing infrared anomalous dimensions purely on-shell, efficiently up to two loops in any massless theory. After introducing the general formalism and reviewing the one-loop recipe, we extract a practical formula that relates two-loop infrared anomalous dimensions to certain two- and three-particle phase space integrals with tree-level form factors of conserved operators. We finally provide several examples of the use of the two-loop formula and comment on some of its formal aspects, especially the cancellation of ‘one-loop squared’ spurious terms. The present version of the paper is augmented with a detailed treatment of the structure of infrared divergences in massless theories of scalars and fermions up to two loops. In the calculation we encounter divergent phase space integrals and show in detail how these cancel among each other as required by the finiteness of the anomalous dimension. As a non-trivial check of the method, we also perform the computation with a standard diagrammatic approach, finding perfect agreement.
Monte Carlo simulations of the underwater detection of illicit war remnants with neutron-based sensors
Authors: Silarski Michał , Sibczyński Paweł , Bezshyyko Oleg , Kapłon Łukasz , Kumar Vinod , Niedźwiecki Szymon , Nowakowski Marek , Moskal Paweł , Sharma Sushil , Sobczuk Franciszek
Published: August 2023

In recent years, the demand for accurate detection and identification of hazardous substances in an aquatic environment, especially in the Baltic Sea, has seen a significant rise, with a specific focus on unexploded ordnance (UXO) containing conventional explosives and various chemical agents, including, but not limited to, mustard gas, Clark I and II and other lethal compounds. These substances pose a significant threat to human health and the environment, and their identification is crucial for effective demining and environmental protection efforts. In this article, a novel approach for fast, remote, and non-destructive recognition of dangerous substances based on a SABAT sensor installed on an ROV is described. The performance of the proposed neutron-based sensor in an aquatic environment was verified based on a series of Monte Carlo simulations for mustard gas, Clark I and II, and TNT, as they are the most common chemical threats at the bottom of the Baltic Sea. The sensor’s ability to accurately discriminate hazardous and non-hazardous materials is described in the paper in terms of the ratio of chlorine to hydrogen (Cl/H), carbon to oxygen (C/O), and nitrogen to hydrogen (N/H) activation lines integrals. The authors also discussed the future directions of work to validate SABAT (Stoichiometry Analysis By Activation Techniques) sensors in the operational environment.
Ten Years into the Belt and Road Initiative in Malaysia: Shift, Continuity and Way Forward
Authors: JAMIL Nur Shahadah
Published: August 2023

After Anwar Ibrahim assumed office in November 2022, Malaysia’s China policy, including its stance towards the Belt and Road Initiative (BRI), was again thrust into the limelight. This paper analyses Malaysia’s responses towards BRI since 2013 and argues that the “shift” is not to abandon its cooperation or adjust its overall foreign policy with China, but to cater for two sets of domestic considerations – the need for development and inter-elite competition, and eventual regime legitimation.
Extending the China-Pakistan Economic Corridor to Afghanistan: Progress and Prospect
Authors: ZHANG Jie
Published: August 2023

China and Pakistan have promoted the China-Pakistan Economic Corridor (CPEC) to Afghanistan after the Taliban took over. China aims to help Afghanistan improve its security situation and expand the Belt and Road Initiative, while Pakistan hopes to expand its strategic depth in Afghanistan against India and to prevent the Tehrik-i-Taliban Pakistan from extending its influence. However, Afghanistan faces multiple challenges in the CPEC, including the turbulent security situation and intervention from the United States, India and other countries.
Making Ethics at Home in Global CS Education: Provoking Stories from the Souths
Authors: Wong-Villacres Marisol , Kutay Cat , Lazem Shaimaa , Ahmed Nova , Abad Cristina , Collazos Cesar , Elbassuoni Shady , Islam Farzana , Singh Deepa , Mayeesha Tasmiah Tahsin , Ujakpa Martin Mabeifam , Zaman Tariq , Bidwell Nicola J.
Published: August 2023

Despite the increase in university courses and curricula on the ethics of computing there are few studies about how computer science (CS) programs should account for the diverse ways ethical dilemmas and approaches to ethics are situated in cultural, philosophical, and governance systems, religions, and languages. We draw on the experiences and insights of 46 university educators and practitioners in Latin America, South-Asia, Africa, the Middle East, and Australian First Nations who participated in surveys and interviews. Our modest study seeks to prompt conversation about ethics and computing in the Global Souths and inform revisions to the Association of Computer Machinery's curricular guidelines for the Society, Ethics and Professionalism knowledge area in undergraduate CS programs. Participants describe frictions between static and anticipatory approaches to ethics in globalised regulations and formal codes of ethics and professional conduct and local practices, values, and impacts of technologies in the Global Souths. Codes and regulations are instruments for international control and their gap with local realities can cause harm, despite local efforts to compensate. However, our insights also illustrate opportunities for university teaching to link more closely to priorities, actions, and experiences in the Global Souths and enrich students’ education in the Global North.
Can Same-right-and-different-left Gestures Be Recognized with Only Right-hand Signals?
Authors: Cao Yidan , Wang Qingshan , Wang Qi , Liu Peng
Published: August 2023

Sign language serves as a bridge between the hearing-impaired and other people. Existing sensor-based approaches tend to only collect data from the dominant hand. Does this signal collection method affect the accuracy of gesture recognition, especially gestures where the dominant hand has the same movement while the non-dominant hand has different movements? The specific gestures are called same-right-and-different-left (SRDL) where the right hand is dominant. This article is the first to propose an SRDL-aware sign language recognition system. First, an SRDL discriminator based on an autoencoder and range classifier is designed to determine whether the gesture is SRDL. Second, an SRDL feature selector based on clustering relationship is presented. Multivariate variational mode decomposition and fast fourier transform are used to obtain the feature expression. Moreover, a clustering relationship algorithm is proposed to dynamically select features for every group of SRDL gestures in the feature expression. Finally, the experimental results show that the average word error rate is 14.3% and decreases by 8.5% and 12.1% compared with Signspeaker and MyoSign, respectively.
Deep Learning Approaches on Image Captioning: A Review
Authors: Ghandi Taraneh , Pourreza Hamidreza , Mahyar Hamidreza
Published: August 2023

Image captioning is a research area of immense importance, aiming to generate natural language descriptions for visual content in the form of still images. The advent of deep learning and more recently vision-language pre-training techniques has revolutionized the field, leading to more sophisticated methods and improved performance. In this survey article, we provide a structured review of deep learning methods in image captioning by presenting a comprehensive taxonomy and discussing each method category in detail. Additionally, we examine the datasets commonly employed in image captioning research, as well as the evaluation metrics used to assess the performance of different captioning models. We address the challenges faced in this field by emphasizing issues such as object hallucination, missing context, illumination conditions, contextual understanding, and referring expressions. We rank different deep learning methods’ performance according to widely used evaluation metrics, giving insight into the current state-of-the-art. Furthermore, we identify several potential future directions for research in this area, which include tackling the information misalignment problem between image and text modalities, mitigating dataset bias, incorporating vision-language pre-training methods to enhance caption generation, and developing improved evaluation tools to accurately measure the quality of image captions.
Physiological Changes in the Levels of Anti-Cytokine Autoantibodies in Early Pregnancy Are Missing in Pregnant Women with Hashimoto’s Thyroiditis
Authors: Erdő-Bonyár Szabina , Simon Diána , Bajnok Anna , Nörenberg Jasper , Serény-Litvai Tímea , Várnagy Ákos , Kovács Kálmán , Hantosi Eszter , Mezősi Emese , Berki Tímea
Published: August 2023

T helper type 1 (Th1) and inflammatory cytokines play essential roles in early pregnancy and also in the pathogenesis of Hashimoto’s thyroiditis (HT). Changes in the serum level of autoantibodies to cytokines, which may be able to modulate their availability and actions have been described in several autoimmune disorders. Yet, no data are available on anti-cytokine autoantibodies either during early pregnancy or in patients with HT. The aim of the study was to measure autoantibodies to inflammatory-, Th1- and Th22-cytokines in serum samples in healthy pregnancy (HP) and in pregnant women with HT (HTP). As pathological autoantibodies are hallmarks of HT, in addition we also measured anti-B-cell activator factor (BAFF) autoantibodies. The measurement was carried out with a Luminex multiplex assay and the Luminex MAGPIX Instrument, age-matched healthy women (HC) and women with HT (HT) were used as controls. In the first trimester of HP, anti-TNFα, anti-IL-8, and anti-IFNγ autoantibodies were significantly decreased, while autoantibodies to BAFF were significantly elevated compared to the HC. However, these alterations were not present in the HTP. Moreover, the levels of autoantibodies to IL-22 and TNFα were significantly increased in HTP compared to the HP. All differences in the levels of the investigated autoantibodies could be detected in the first trimester of pregnancies except for anti-IL-22 autoantibodies. According to our results we can conclude that alterations in the levels of autoantibodies to inflammatory and Th1 cytokines are physiological in the first trimester of pregnancy and their disturbance can be associated with autoimmune conditions such as HT.
An Integrated Approach to Scheduling B-CAVs in Container Terminals considering Battery Management
Authors: Wang Shuo , Luo Jiliang , Wu Weimin , Zhang Dahai , Zhang Tao
Published: August 2023

With the aim of promoting environmental sustainability and enhancing transport efficiency, battery-powered connected and automated vehicles (B-CAVs) are employed to replace diesel-powered ones in horizontal transport systems (HTSs) of container terminals. The operational efficiency of an HTS can be increased by the cooperation of B-CAVs. However, it is time-consuming to charge them. Therefore, their battery management becomes a critical issue of a transport schedule. To run container terminals more economically and efficiently, this work proposes an integrated scheduling approach to B-CAVs tasks’ dispatch and route planning, where battery management is taken into account. An integer programming model is constructed with the goal of minimizing the total travel distance. Then, a sustainable charging policy is designed to ensure the consistent transport capacity of an HTS. Furthermore, a congestion-free path plan-based improved genetic algorithm is presented to obtain a near-optimal plan for dispatching B-CAVs to perform transporting and charging operations. A series of experiments are carried out to verify the effectiveness and efficiency of our approach.
Outcomes of Pain Management Training for the Fourth- and Fifth-Year Medical Students
Authors: Saeki Ayano , Takao Yumiko , Suzuki Keiichiro , Hirose Munetaka
Published: August 2023

Pain management is a major medical issue. However, current medical education in Japan is inadequate with regard to training students to properly assess patients with acute and chronic pain and plan their treatment. Therefore, starting in 2019, Hyogo Medical University established a multidisciplinary educational system to better train medical students to provide pain care. The course, called clinical pain study, is offered to fourth- and fifth-year medical students. Fourth-year students learn the scientific aspects of pain through clinical practice. In this study, we assessed students’ understanding of pain management based on the results of pretests and posttests performed before and after their practicum. These tests were administered from November 2019 to April 2022 to 263 fourth- and fifth-year medical students who took the clinical pain study class. The test results were compared in terms of the percentage of correct answers and the total score for each question using McNemar’s chi-square test and paired t-tests, respectively. The results showed a significant improvement in the mean of the total score, confirming the improvement in medical students’ knowledge (6.43 vs. 7.35 points;

p
<
0.001

). Based on the results, overall, pain education at the university has had positive outcomes and will therefore be continued in the future.
Hormonal-Receptors-Positive and HER2-Negative Patients with Metastatic Breast Cancer Treated with First-Line Palbociclib and Hormonal Therapy: Impact of First-Cycle Neutropenia and Dose Reduction on Therapeutic Outcome
Authors: Elnaghi Khaled Abd Elaziz Ahmed , Alghanmi Hosam Ali , Elsamany Shereef Ahmed , Almarzoki Fathia , Elsafty Mohamed , Jaffal Mohammad
Published: August 2023

Background. CDK 4/6 inhibitors with hormonal therapy are the standard first-line therapy in metastatic hormonal receptors (HR)-positive and HER2-negative breast cancer. This study aims to assess the impact of neutropenia with 1st cycle, dose reduction, HER2-low status, and other clinicopathological factors on survival outcomes with the first-line palbociclib and hormonal therapy. Patients and Methods. In this retrospective study, we recruited patients with metastatic HR-positive and HER2-negative breast cancer. Neutropenia with 1st cycle, palbociclib dose reduction in addition to different clinicopathological and survival data were checked in patients’ medical records. Survival outcomes were compared according to the abovementioned factors. Results. We recruited 150 patients who received first-line palbociclib with hormonal therapy. 86% of patients developed 1st cycle neutropenia which was more common in patients with high Ki67. Dose reduction was recorded in 46.7% of patients and it was more common in patients with higher Allred scores (scores 7–8). The median progression-free survival (PFS) of the study group was 22 months. No significant difference was observed in PFS according to the 1st cycle of neutropenia or grade of neutropenia. Similarly, no difference in PFS according to palbociclib dose reduction and HER2 low status was observed. Only the Allred score and having a single site of metastasis had an independent significant relation with PFS. The median overall survival (OS) of the study group was 39 months. No significant difference was observed in OS according to the 1st cycle neutropenia, grade of neutropenia, palbociclib dose reduction, and HER2-low status. Only the Allred score and having a single site of metastasis had an independent significant relation with OS. In addition, no difference was observed in PFS and OS according to ECOG PS (2 vs. 0-1) or menopausal status. Conclusion. No significant impact of the 1st cycle neutropenia, dose reduction, having ECOG PS2, menopausal status, or HER2 low status on survival outcome was observed. Survival outcome was significantly better in patients with single metastatic sites and higher ER-Allred scores.
A Sensitive Method for Detecting Beauveria bassiana, an Insecticidal Biocontrol Agent, Population Dynamics, and Stability in Different Substrates
Authors: Gu Zepei , Chen Lijie , Zhang Weixing , Su Pin , Zhang Deyong , Du Xiaohua , Peng Qianze , Liu Zhuoxin , Liao Xiaolan , Liu Yong
Published: August 2023

Beauveria bassiana is a well-known insecticidal biocontrol agent. Despite its broad field applications, its survival, colonization, and stability under field conditions remained unclear, mainly due to the lack of a quick and reliable detection method. In this study, we developed a quantitative real-time PCR technology to monitor the stability and population dynamics of B. bassiana in different substrates (water, soil, and on the cotton leaves surface), different spores of B. bassiana applied on Chinese cabbage leaves surface, and the lethality of Pieris rapae spraying with different spores of B. bassiana. Our results showed a decreased concentration of B. bassiana DNA in all three substrates from the 1st day till 9th day of post inoculation (dpi) period, possibly due to the death of B. bassiana. After this decrease, a quick and significant rebound of B. bassiana DNA concentration was observed, starting from the 11th dpi in all three substrates. The B. bassiana DNA concentration reached the plateau at about 13th dpi in water and 17th dpi in the soil. On cotton leaves surface, the B. bassiana DNA concentration reached the highest level at the 17th dpi followed by a small decline and then stabilized. This increase of DNA concentration suggested recovery of B. bassiana growth in all three substrates. We found that the most suitable killing effectiveness of P. rapae was the 1.0 × 107 spores/mL of B. bassiana. In summary, we have established a detection technology that allows a fast and reliable monitoring for the concentration and stability of B. bassiana under different conditions. This technology can benefit and help us in the development of proper management strategies for the application of this biocontrol agent in the field.
FDA Approval Summary: Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma
Authors: Telaraja Deepti , Kasamon Yvette L. , Collazo Justin S. , Leong Ruby , Wang Kun , Li Ping , Dahmane Elyes , Yang Yuching , Earp Justin , Grimstein Manuela , Rodriguez Lisa R. , Theoret Marc R. , Gormley Nicole J.
Published: August 2023

In January 2023, the FDA granted accelerated approval to pirtobrutinib for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. Approval was based on BRUIN, a single-arm study of pirtobrutinib monotherapy in patients with B-cell malignancies. Efficacy was based on independent review committee–assessed overall response rate (ORR) supported by durability of response in 120 patients with relapsed or refractory MCL who had received a prior BTK inhibitor and received the approved pirtobrutinib dosage of 200 mg once daily. The ORR was 50% [95% confidence interval (CI), 41–59], and the complete response rate was 13% (95% CI, 7–20), with an estimated median duration of response of 8.3 months. The most common nonhematologic adverse reactions were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Warnings and Precautions in labeling include infection, hemorrhage, cytopenias, atrial arrhythmias, and second primary malignancies. Postmarketing studies were required to evaluate longer-term safety of pirtobrutinib and to verify the clinical benefit of pirtobrutinib. This article summarizes key aspects of the regulatory review, including the indication statement, efficacy and safety considerations, and postmarketing requirements.
BCL2 Inhibition Reveals a Dendritic Cell–Specific Immune Checkpoint That Controls Tumor Immunosurveillance
Authors: Zhao Liwei , Liu Peng , Mao Misha , Zhang Shuai , Bigenwald Camille , Dutertre Charles-Antoine , Lehmann Christian H.K. , Pan Hui , Paulhan Nicolas , Amon Lukas , Buqué Aitziber , Yamazaki Takahiro , Galluzzi Lorenzo , Kloeckner Benoit , Silvin Aymeric , Pan Yuhong , Chen Hui , Tian Ai-Ling , Ly Pierre , Dudziak Diana , Zitvogel Laurence , Kepp Oliver , Kroemer Guido
Published: August 2023

We developed a phenotypic screening platform for the functional exploration of dendritic cells (DC). Here, we report a genome-wide CRISPR screen that revealed BCL2 as an endogenous inhibitor of DC function. Knockout of BCL2 enhanced DC antigen presentation and activation as well as the capacity of DCs to control tumors and to synergize with PD-1 blockade. The pharmacologic BCL2 inhibitors venetoclax and navitoclax phenocopied these effects and caused a cDC1-dependent regression of orthotopic lung cancers and fibrosarcomas. Thus, solid tumors failed to respond to BCL2 inhibition in mice constitutively devoid of cDC1, and this was reversed by the infusion of DCs. Moreover, cDC1 depletion reduced the therapeutic efficacy of BCL2 inhibitors alone or in combination with PD-1 blockade and treatment with venetoclax caused cDC1 activation, both in mice and in patients. In conclusion, genetic and pharmacologic BCL2 inhibition unveils a DC-specific immune checkpoint that restrains tumor immunosurveillance.

Significance:

BCL2 inhibition improves the capacity of DCs to stimulate anticancer immunity and restrain cancer growth in an immunocompetent context but not in mice lacking cDC1 or mature T cells. This study indicates that BCL2 blockade can be used to sensitize solid cancers to PD-1/PD-L1–targeting immunotherapy.

This article is featured in Selected Articles from This Issue, p. 2293
Human Rights and the Global Plastics Treaty to Protect Health, Ocean Ecosystems and Our Climate
Authors: O’Meara Noreen
Published: August 2023

The global plastics pollution crisis has multiple visible and invisible effects on marine, land and air environments. Fossil fuel-based plastics production is projected to triple by 2060, driving a plastics lifecycle that exacerbates climate change, contaminates ecosystems and poses risks to human rights, especially the human right to health. Existing governance measures help tackle plastics waste pollution but cannot effectively address its systemic nature. Drafting a Global Plastics Treaty, due for adoption in 2025, is an opportunity to design ambitious international plastics governance. This article argues for a human rights-based approach to the proposed treaty’s framing and substance by integrating, in particular, the human right to health, supplemented by the human right to a healthy environment. Embedding human rights considerations through a precautionary and preventative approach, shifting responsibility to polluters and showing concern for intergenerational equity would combat plastics pollution, accelerate climate action, protect ocean ecosystems and safeguard human rights.
Regular Treadmill Exercise Improves the Spinal Cord Injury Repair in a Rat Model Treated with Menstrual Blood Stem Cells and Curcumin-Loaded Nanocomposite Hydrogel: An In Vitro and In Vivo Study
Authors: Cong Rui , Li Fenglei
Published: August 2023

In the current study, the synergistic healing efficacy of regular treadmill exercise and administration of menstrual blood stem cells and curcumin-loaded calcium alginate hydrogel was investigated. In Vitro studies were used to characterize the hydrogel system In Vitro.
Various validation methods including BBB assay, histopathological examinations, and gene expression studies were used to assess the healing efficacy of different groups. Study showed that treadmill exercise and the hydrogels loaded with both menstrual blood stem cells and curcumin significantly
improved the spinal cord injury repair through upregulation of pro-healing genes.
HOXD9 Stimulates the Process of Colorectal Carcinoma by Regulating KLK9
Authors: Ai Chunlong , Xu Zhi , Wang Yujue , Huang Baolei , Tai Jiandong
Published: August 2023

Colorectal carcinoma (CRC) is a common tumor in the digestive system. This study aims to elucidate the possible relationship between abnormally expressed HOXD9 and the malignant process of CRC. HOXD9 levels were analyzed in CRC and adjacent non-tumoral tissues to evaluate its prognostic
value in CRC patients. Knockdown of HOXD9 was performed, and the proliferative and migratory capacities of LoVo and LS513 cells were assessed using CCK-8, transwell, and wound healing assays. Bioinformatic analysis and dual-luciferase reporter assay revealed the interaction between HOXD9 and
KLK9. Rescue experiments were conducted to elucidate the co-regulation of HOXD9 and KLK9 on CRC cell behaviors. HOXD9 was upregulated in CRC tissues, and high level of HOXD9 predicted poor prognosis in CRC patients. HOXD9 was identically upregulated in CRC cell lines, especially LoVo and LS513
cells, which were used for generating HOXD9 knockdown models by transfection of sh-HOXD9. Knockdown of HOXD9 weakened proliferative and migratory capacities in CRC cells. KLK9 was the target binding HOXD9, which was downregulated in CRC tissues and cell lines. Knockdown of KLK9 reversed the
inhibited proliferative and migratory capacities in CRC cells owing to HOXD9 knockdown. Highly expressed HOXD9 in CRC tissues is closely linked to the prognosis. HOXD9 stimulates CRC cells to proliferate and migrate by upregulating KLK9.