bluuebunny/crossref_metadata_2025 huggingface dataset:
ESG and overcapacity governance evidence from Chinese listed firms
Authors: Ou Dingyu , Hou Siyao , Zhou Fenfang
Published: August 2024

This research examines how firms' environmental, social and governance (ESG) performance impacts their capacity utilisation using data from listed firms in China from 2009 to 2022. We find that firms' ESG performance significantly elevates their capacity utilisation with an inverted U‐shaped relationship. All three dimensions of ESG—environmental performance, social responsibility and governance—positively affect capacity utilisation, addressing gaps in enhancing firms' capacity utilisation through ESG practices. We identify an indirect transmission channel through which firms' ESG practices influence capacity utilisation, marking a pioneering discovery in our study. Using structural equation modelling (SEM), we confirm that firms' ESG practices enhance capacity utilisation by improving competitiveness and customer stickiness. Additionally, we discuss potential heterogeneity in the impact of ESG performance on capacity utilisation, considering factors such as ownership structure, industry, financial constraints and equity arrangements. Our findings provide insights for governments and companies aiming to incorporate ESG principles into their decision‐making processes to enhance capacity utilisation.
Benzimidazole–Oxadiazole Hybrids—Development in Medicinal Chemistry: An Overview
Authors: Bhat Raveendra Madhukar , Hegde Venkatraman , Budagumpi Srinivasa , Adimule Vinayak , Keri Rangappa S.
Published: August 2024

To increase the success rate of drug discovery, one practical strategy is to begin molecular hybridisation. The presence of two or more pharmacophores in a single unit leads to a pharmacological potency greater than the sum of each individual moiety's potency. Heterocyclic compounds are very widely distributed in nature and are essential for life activities. Benzimidazole and oxadiazole are privileged structures in medicinal chemistry and are widely used in drug discovery and development due to their vast biological properties. The drug‐like properties (like pharmacokinetics and pharmacodynamics) of the individual scaffolds can be improved by benzimidazole–oxadiazole chimeric molecules via a molecular hybridisation approach. Benzimidazole and oxadiazole cores can either be fused or incorporated using either functional groups/bonds. Over the last few decades, drug discovery scientists have predicted that these moieties could be interconnected to yield a novel or modified hybrid compound. Benzimidazole and oxadiazole hybrids were identified as the most potent anticancer, antimicrobial, anti‐inflammatory, antioxidant, anticonvulsant, antidepressant, antihypertensive and antitubercular agents. In this context, the present review describes the biological properties of benzimidazole–oxadiazole (1,3,4 and 1,2,4) hybrids, their possible structure–activity relationship and the mechanism of action studies presented. This review article is intended to stimulate fresh ideas in the search for rational designs of more active and less toxic benzimidazole–oxadiazole hybrid prospective therapeutic candidates, as well as more effective diagnostic agents and pathologic probes.
Remoteness‐attributable financial inequality in dental service utilization in Australian older adults: A Blinder‐Oaxaca decomposition
Authors: Ghanbarzadegan Arash , Ju Xiangqun , Sohn Woosung , Jamieson Lisa
Published: August 2024

Objective

Oral health is often overlooked in ageing health issues, despite its impact on overall health and quality of life. Older Australians, especially those in rural and remote areas, face difficulties accessing oral health services. The aim of the study was to investigate the factors that contribute to financial barriers to accessing dental services among the ageing population in Australia in relation to their residential location.

Method

The study included a weighted sample of Australian adults aged 65 years and over from a population‐based survey called the National Study of Adult Oral Health (NSAOH) conducted in 2017–18. Descriptive analysis was conducted and generated cross‐tabulation tables to investigate the distributions of the outcome, exposure and covariates, including Sex, Education level (the highest level of education), Equivalised household income, Dental insurance, Concession card ownership, Difficulty paying a dental bill and last dental visit. Blinder‐Oaxaca decomposition counterfactual analysis was used to explore the potential impact of a person's residence on their financial difficulty accessing dental services.

Results

The findings showed that 26.2% (95% CI: 24.3–29.3) of major city residents and 30.1% (95% CI: 26.9–33.3) of rural residents avoided or delayed dental visits due to cost. The decomposition analysis indicated that 53.8% of the disparities in the prevalence of avoided or delayed dental visits due to cost were explained by the selected variables, while 46.2% remained unexplained. The explanatory variable with the largest contribution was difficulty paying a $200 dental bill, accounting for 62.4% of the differences, followed by dental insurance, last dental visit and equivalised household income, which explained 42.1%, 20.8% and 14.9% of the differences, respectively.

Conclusion

Regional/remote populations experience more financial barriers to accessing dental care than major city populations and the identified factors explain a significant proportion of these disparities. Based on the study findings, recommendations include expanding public dental service coverage, evaluating concession card mechanisms and advocating for regular dental visits to mitigate disparities in dental care access.
Comparative analysis of dental implant placement accuracy: Semi‐active robotic versus free‐hand techniques: A randomized controlled clinical trial
Authors: Yang Fan , Chen Jianping , Cao Ruijue , Tang Qingwei , Liu Haiyan , Zheng Yuchen , Liu BeiLei , Huang Min , Wang Zhenshi , Ding Yude , Wang Linhong
Published: August 2024

Background

Robot‐assisted implant surgery has emerged as a novel digital technology, and the accuracy need further assessment.

Purpose

This study aimed to compare the accuracy of single dental implant placement between a novel semi‐active robot‐assisted implant surgery (RAIS) method and the conventional free‐hand implant surgery (FHIS) method through a multicenter, randomized controlled clinical trial.

Materials and Methods

Patients requiring single dental implant placement were recruited and randomized into RAIS and FHIS group. Deviations at the platform, apex, and angle between the planned and final implant positions were assessed in both groups. Additionally, the evaluation of instrument and surgical complications was examined.

Results

A total of 140 patients (median age: 35.35 ± 12.55 years; 43 males, 97 females) with 140 implants from four different research centers were included, with 70 patients (70 implants) in the RAIS group and 70 patients (70 implants) in the FHIS group. In the RAIS and FHIS groups, the median platform deviations were 0.76 ± 0.36 mm and 1.48 ± 0.93 mm, respectively (p < 0.001); median apex deviations were 0.85 ± 0.48 mm and 2.14 ± 1.25 mm, respectively (p < 0.001); and median angular deviations were 2.05 ± 1.33° and 7.36 ± 4.67°, respectively (p < 0.001). Similar significant difference also presented between RAIS and FHIS group in platform vertical/horizontal deviation, apex vertical/horizontal deviation. Additionally, implants with self‐tapping characteristics exhibited significantly larger deviations compared with those without self‐tapping characteristics in the RAIS group. Both RAIS and FHIS methods demonstrated comparable morbidity and safety pre‐ and post‐operation.

Conclusions

The results indicated that the RAIS method demonstrated superior accuracy in single dental implant placement compared with the FHIS method. Specifically, RAIS exhibited significantly smaller deviations in platform, apex, and angular positions, as well as platform and apex vertical/horizontal deviations.

This clinical trial was not registered prior to participant recruitment and randomization. https://www.chictr.org.cn/showproj.html?proj=195045.
Measuring the performance of Antarctic Treaty decision‐making
Authors: Gardiner Natasha Blaize , Gilbert Neil , Liggett Daniela , Bode Michael
Published: August 2024

Agreements reached at the Antarctic Treaty Consultative Meetings (ATCMs) are among the primary means for addressing Antarctic conservation and environmental protection issues. However, according to contemporary scholars, Antarctic Treaty decision‐making is becoming increasingly unresponsive to the rising environmental challenges in the region. We assessed the performance of Antarctic Treaty decision‐making by measuring the rate and diversity of decision‐making over the last 6 decades. To measure the rate, we counted the number of inputs and outputs of ATCMs and calculated the time taken for legally binding outputs to enter into force. To measure diversity, we calculated the range of topics addressed by the inputs and outputs of ATCMs. The average number of agreements reached per ATCM increased from 1961 to 2022. Although the diversity of Antarctic topics discussed at ATCMs remained consistently high, the diversity of topics on which legally binding agreements were adopted declined significantly. Antarctic issues—including those of highest priority—are now almost entirely dealt with through nonbinding, soft‐law agreements. It is plausible that this move away from binding decisions reflects a dynamic governance institution evolving to respond to new pressures. However, we suggest that the change reveals a concerning shift in decision‐making behavior and performance, unique to the treaty's history. Soft law is beneficial in some cases, but its overuse diminishes accountability and transparency, significantly reducing the parties’ abilities to understand and measure their performance, including the outcomes and impacts of decisions. Although the rate and diversity of ATCM inputs and outputs provide only a partial view of decision‐making performance, the exploration of these metrics provides a foundation for asking essential questions about the impacts of Antarctic Treaty governance on the region's environmental protection and conservation.
Partner‐Specific Adaptation in Disfluency Processing
Authors: Yoon Si On , Brown‐Schmidt Sarah
Published: August 2024

Speakers tend to produce disfluencies when naming unexpected or complex items; in turn, when perceiving disfluency, listeners tend to expect upcoming reference to items that are unexpected or complex to name. In two experiments, we examined if these disfluency‐based expectations are routine, or instead, if they adapt to the way the speaker uses disfluency in the current context in a talker‐specific manner. Participants listened to instructions to look at objects in contexts with several images, some of which lacked conventional names. We manipulated the co‐occurrence of disfluency and reference to novel versus familiar objects in a single talker situation (Experiment 1) and in a multi‐talker situation (Experiment 2). In the predictive condition, disfluent expressions referred to novel objects, and fluent expressions referred to familiar objects. In the nonpredictive condition, fluent and disfluent trials referred to either familiar or novel objects. Participants’ gaze revealed that listeners more readily predicted familiar images for fluent trials and novel images for disfluent trials in the predictive condition than in the nonpredictive condition. In sum, listeners adapted their expectations about upcoming words based on recent experience with disfluency. Disfluency is not invariably processed, but instead a cue that is flexibly interpreted depending on the local context even in a multi‐talker setting.
The impact of dynamic caudal type homeobox 2 expression on the differentiation of human trophoblast lineage during implantation
Authors: Rong Lujuan , Xiang Lifeng , Ai Zongyong , Niu Baohua , Wang Yaqing , Yin Yu , Feng Chun , Shi Gaohui , Chen Tingwei , Yang Jie , Luo Xi , Bai Yun , Zhou Xiaoting , Liu Xiaoping , Zheng Haishan , Ke Yang , Li Tianqing , Wu Ze
Published: August 2024

The trophoblast lineage differentiation represents a rate‐limiting step in successful embryo implantation. Adhesion, invasion and migration processes within the trophoblast are governed by several transcription factors. Among them, CDX2 is a critical regulator shaping the destiny of the trophoblast. While its altered expression is a linchpin initiating embryo implantation in mice, the precise influence of CDX2 on the functionality and lineage differentiation of early human trophoblast remains unclear. In this study, we employed well‐established human trophoblast stem cell (hTSC) lines with CDX2 overexpression coupled with a 3D in vitro culture system for early human embryos. We revealed that the downregulation of CDX2 is a prerequisite for syncytialization during human embryo implantation based on immunofluorescence, transcriptome analysis, CUT‐tag sequencing and the construction of 3D human trophoblast organoids. While CDX2 overexpression inhibited syncytialization, it propelled hTSC proliferation and invasive migration. CDX2 exerted its influence by interacting with CGA, PTGS2, GCM1, LEF1 and CDH2, thereby hindering premature differentiation of the syncytiotrophoblast. CDX2 overexpression enhanced the epithelial–mesenchymal transition of human trophoblast organoids. In summary, our study provides insights into the molecular characteristics of trophoblast differentiation and development in humans, laying a theoretical foundation for advancing research in embryo implantation.
Alternating electric fields transform the intricate network of tumour vasculature into orderly parallel capillaries and enhance the anti‐angiogenesis effect of bevacizumab
Authors: Shen Lin , Li Shuai , Wang Yalin , Yin Yi , Liu Yiting , Zhang Yunlei , Zheng Xuesheng
Published: August 2024

The search for effective strategies to target tumour angiogenesis remains a critical goal of cancer research. We present a pioneering approach using alternating electric fields to inhibit tumour angiogenesis and enhance the therapeutic efficacy of bevacizumab. Chicken chorioallantoic membrane, cell viability and in vitro endothelial tube formation assays revealed that electric fields with a frequency of 1000 kHz and an electric intensity of 0.6 V/cm inhibited the growth of vascular endothelial cells and suppressed tumour‐induced angiogenesis. In an animal U87MG glioma model, 1000 kHz electric fields inhibited tumour angiogenesis and suppressed tumour growth. As demonstrated by 3D vessel analysis, tumour vasculature in the control group was a stout, interwoven network. However, electric fields transformed it into slim, parallel capillaries that were strictly perpendicular to the electric field direction. This architectural transformation was accompanied by apoptosis of vascular endothelial cells and a notable reduction in tumour vessel number. Additionally, we found that the anti‐angiogenesis and tumour‐suppression effects of electric fields synergised with bevacizumab. The anti‐angiogenic mechanisms of electric fields include disrupting spindle formation during endothelial cell division and downregulating environmental angiogenesis‐related cytokines, such as interleukin‐6, CXCL‐1, 2, 3, 5 and 8, and matrix metalloproteinases. In summary, our findings demonstrate the potential of alternating electric fields (AEFs) as a therapeutic modality to impede angiogenesis and restrain cancer growth.
Comparative Efficacy and Safety of Immunotherapy on Non–Small Cell Lung Cancer Patients With Brain Metastases: A Systematic Review and Network Meta‐Analysis
Authors: Lyu Tianyi , Sun Bo , Yang Daowen , Zhao Xirui , Wang Ruoshui , Shu Xinyang , Li Demin , Chen Hong
Published: August 2024

Background

Growing evidence suggests that immunotherapy has a positive effect on non–small cell lung cancer (NSCLC) patients with brain metastases (BMs). However, it remains unclear which type of immunotherapy is more efficient. The aim of this network meta‐analysis (NMA) was to compare the efficacy and safety of different immunotherapy types and determine the optimal option.

Method

Four databases (PubMed, Cochrane Library databases, Embase, and Web of Science) and ClinicalTrial.gov were searched from inception until January 26, 2023. Randomized controlled trials (RCTs), prospective nonrandomized trials, or observational studies investigating NSCLC patients with BMs treated by immunotherapy were included. The quality of the included studies was evaluated using the Cochrane risk of bias (ROB) tool and the Newcastle‐Ottawa Scale (NOS). The efficacy of immunotherapy on NSCLC patients with BMs was evaluated using frequentist random‐effects NMA.

Result

Eleven studies from 1560 citations, encompassing 1437 participants, were included in this NMA. Statistical analysis showed that pembrolizumab (SMD = 4.35, 95% CI [2.21, 6.60]) and nivolumab+ipilimumab (SMD = 3.81, 95% CI [1.21, 6.40]) could improve overall survival (OS). Pembrolizumab (SMD = 3.32, 95% CI [2.75, 3.90]) demonstrated better effects in improving the overall response rate (ORR). No significant difference in adverse event (AE) was observed between immunotherapy and chemotherapy.

Conclusion

Our findings indicated that pembrolizumab was the most promising immunotherapy for NSCLC patients with BMs. Nivolumab+ipilimumab might be an alternative choice to improve OS.

Limitation

Inconsistency tests were not performed because of the scarcity of direct comparison. Besides, high heterogeneity was observed in our NMA.
Novel harm reduction measures at music festivals in Australia: Pilot implementation of the Emerging Drugs Network of Australia–Victoria toxicosurveillance methodology
Authors: Syrjanen Rebekka , Dutch Martin , Greene Shaun L. , Lyons Tom , McKinnon Ginny , Gerostamoulos Dimitri , Schumann Jennifer L. ,   the EDNAV Project Research Group
Published: August 2024

Introduction

Harm reduction strategies at music festivals seek to create a safer environment for patrons. The Emerging Drugs Network of Australia–Victoria (EDNAV) project is a state‐wide toxicosurveillance network that derives drug intelligence from a sample of patients presenting to hospital with illicit drug‐related toxicity. This publication describes the preliminary outcomes of conducting toxicosurveillance for critically unwell festival patrons within on‐site medical facilities.

Methods

Blood samples were collected from patrons who presented with severe illicit drug‐related toxicity across three festivals (2022/2023). Blood samples were analysed via liquid chromatography–tandem mass spectrometry for over 700 pharmaceutical and illicit drugs.

Results

There were 1603 individual medical encounters across the festivals, 228 of which were illicit drug related. A blood sample was collected for 24 patients, with a median age of 22 years (range 18–39 years). A median of two drugs (range 1–5 drugs) were reported and four drugs (range 0–8 drugs) were analytically confirmed per patient. The most frequently reported exposures were congruent with analytical results, 3,4‐methylenedioxymethamphetamine (reported n = 17, detected n = 20), ketamine (reported n = 9, detected n = 13) and cocaine (reported n = 9, detected n = 12). An unreported illicit drug and/or new psychoactive substance (NPS) was detected in 18 patients, including methylamphetamine (n = 10), a cathinone (n = 7), benzodiazepine‐type NPS (n = 6), N‐ethylamphetamine (n = 1), 3‐hydroxyphencyclidine (n = 1) and/or 4‐hydroxy‐N‐methyl‐N‐isopropyltryptamine (n = 1).

Discussion and Conclusions

EDNAV toxicosurveillance serves as an additional tool within a multi‐faceted approach to harm reduction at festivals. Continued data collection will allow for the characterisation of high‐risk drug use patterns to provide evidence‐based messaging to festival patrons and key stakeholders.
Ten‐year progression of obesity‐related complications in a population with overweight and obesity in the UK: A retrospective open cohort study
Authors: Pearson‐Stuttard Jonathan , Holloway Sara , Sommer Matthiessen Kasper , Thompson Andrew , Capucci Silvia
Published: August 2024

Aim

To assess the prevalence of individual obesity‐related complications (ORCs) and multimorbidity (≥ 1, ≥ 2 and ≥ 3 ORCs), and multimorbidity‐associated healthcare costs, over 10 years.

Methods

This retrospective open cohort study used Discover, a UK database of linked primary and secondary electronic health records. Adults were stratified by body mass index (BMI; overweight: 25‐< 30 kg/m2; obesity class I: 30‐< 35 kg/m2; obesity class II: 35‐< 40 kg/m2; obesity class III: ≥ 40 kg/m2). Outcomes by year since baseline were assessed for serial cross sections across the study period (1 January 2004 to 31 December 2019; the index date was the date of first eligible BMI measurement).

Results

Across 1 410 146 individuals (overweight: 1 008 101; obesity class I: 278 782; obesity class II: 80 621; obesity class III: 42 642), ORC prevalence was higher in successive BMI groups, and increases over time were generally greater for obesity relative to overweight. In those with ORC multimorbidity, both higher BMI and the presence of more ORCs were associated with higher annual per‐person healthcare costs. Costs increased over time in those individuals with obesity and one or more ORC, as well as in those with obesity and two or more ORCs.

Conclusions

Higher BMI was associated with higher baseline ORC prevalence and a greater increase in ORC prevalence over time, and with higher healthcare costs in those with multimorbidity. To reduce the burden of overweight and obesity on patients and healthcare systems, the presence, number and type of ORCs should be considered in developing effective, targeted prevention and management care pathways.
Sweetened beverages and atrial fibrillation in people with prediabetes or diabetes
Authors: Gan Xiaoqin , Ye Ziliang , Zhang Yuanyuan , He Panpan , Liu Mengyi , Zhou Chun , Zhang Yanjun , Yang Sisi , Huang Yu , Xiang Hao , Qin Xianhui
Published: August 2024

Aim

To assess the association of intake of sugar‐sweetened beverages (SSBs), artificially sweetened beverages (ASBs) and natural juices (NJs) with new‐onset atrial fibrillation (AF) in people with prediabetes or diabetes.

Methods

A total of 31 433 participants with prediabetes and diabetes from the UK Biobank were included. Information on the intake of SSBs, ASBs and NJs was accessed by 24‐hour dietary recalls from 2009 to 2012. The study outcome was new‐onset AF.

Results

During a median follow‐up of 12.0 years, 2470 (7.9%) AF cases were documented. Both the intake of SSBs (per 1 unit/day increment; adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI]: 1.04‐1.18) and ASBs (per 1 unit/day increment; adjusted HR = 1.08; 95% CI: 1.02‐1.14) were linearly and positively associated with new‐onset AF, while NJ intake was not significantly associated with new‐onset AF (per 1 unit/day increment; adjusted HR = 1.00; 95% CI: 0.93‐1.08). Accordingly, compared with non‐consumers, participants who consumed more than one unit per day of SSBs (adjusted HR = 1.30; 95% CI: 1.11‐1.53) or ASBs (adjusted HR = 1.21; 95% CI:1.05‐1.40) had an increased risk of AF. Substituting 1 unit/day of NJs for SSBs was associated with a 9% (adjusted HR = 0.91; 95% CI: 0.83‐0.99) lower risk of new‐onset AF, while replacing SSBs with ASBs was not significantly associated with new‐onset AF (adjusted HR = 0.97; 95% CI: 0.89‐1.06).

Conclusions

Both the intake of SSBs and ASBs were linearly and positively associated with new‐onset AF, while NJ intake did not show a significant association with AF in people with prediabetes or diabetes. Replacing an equivalent amount of SSB intake with NJs, but not ASBs, was associated with a lower risk of AF.
Peripheral immune profile and neutrophil‐to‐lymphocyte ratio in progressive supranuclear palsy: Case–control study and meta‐analysis
Authors: Muñoz‐Delgado Laura , Luque‐Ambrosiani Antonio , Zamora Belén Benítez , Macías‐García Daniel , Jesús Silvia , Adarmes‐Gómez Astrid , Ojeda‐Lepe Elena , Carrillo Fátima , Mir Pablo
Published: August 2024

Background and purpose

Peripheral inflammation is probably involved in the pathogenesis of progressive supranuclear palsy (PSP) and it may be a common feature with Parkinson's disease (PD). The peripheral immune profile in PSP remains unclear, as well as whether the inflammatory pathways differ from those in PD. The neutrophil‐to‐lymphocyte ratio (NLR) has been proven to be a well‐established biomarker of systemic inflammation. This study aimed to evaluate the peripheral immune profile in PSP compared with PD.

Methods

A cross‐sectional study was conducted including patients with PSP and PD and healthy controls (HCs). Leukocyte subpopulations and the NLR were measured in peripheral blood. Multivariate linear regression and post hoc tests were applied. Electronic databases were searched in November 2023 to perform meta‐analyses to clarify the peripheral immune profile in PSP.

Results

Our cohort included 121 patients with PSP, 127 patients with PD and 266 HCs. The NLR was higher in PSP and PD compared with HCs. PSP had a higher neutrophil count compared with HCs. Whilst a lower lymphocyte count was found in PD compared with HCs, the lymphocyte count did not differ between PSP and HCs. The meta‐analyses supported this immune profile.

Conclusions

PSP and PD show an increased peripheral inflammation and a higher NLR compared with HCs. Different pathogenic inflammatory mechanisms are probably involved in PSP and PD, since in PSP this altered peripheral immune profile is mainly driven by neutrophils. Understanding the neutrophils' role in PSP may allow for the development of targeted therapies.
Strangles vaccination: A current European perspective
Authors: Rendle David , Bowen Mark , Cavalleri Jessika , De Brauwere Nicolas , Grondahl Gittan , van Maanen K. , Newton J. Richard
Published: August 2024

Development of a subunit vaccine (Strangvac) from fusion of recombinant Streptococcus equi proteins offers a new tool in the management of infection with Streptococcus equi subspecies equi. Experience to date indicates that the vaccine is effective in limiting disease spread, and through inclusion of only the desired proteins needed for induction of an effective immune response, the safety profile appears far better than with previous vaccines. Published reports of the use of the vaccine are limited, and to date, vets have had limited information upon which to make informed decisions on the potential benefits of this novel vaccine. This article was developed to share the collective experience of the authors in using Strangvac and to highlight potential benefits of integrating vaccination alongside biosecurity measures in controlling ‘strangles’. This article reviews the use of vaccination prior to movement, in the face of outbreaks and also discusses use in mares and foals. Safety and the benefits of differentiating vaccinated from infected animals are also discussed. The reader should consider the level of evidence upon which the recommendations are based as it is frequently weak and limited to anecdotal reports or interpretation of unpublished data. The recommendations made are certain to be revised or replaced as new evidence comes forward but provide a basis for practitioners to implement vaccination strategies based on what is known currently. At times, the authors' recommendations deviate from those that were initially put down in the summary of product characteristics. This comes as a result of clinical experience that has been gained since the initial experimental studies were performed prior to registration. Veterinary surgeons using the vaccine outside of the regimen set down in the summary of product characteristics should be cognisant of their local legal framework and should ensure that they have informed consent to do so.
Computed tomographic findings of a nasal neuroendocrine neoplasm with intracranial extension in a horse
Authors: Giorio Maria Elisabetta , Mitchell Jordan L. , Priestnall Simon L. , Dunkel Bettina , Dash Rupert F. , Berner Dagmar
Published: August 2024

A 20‐year‐old Irish Sport Horse gelding was presented to the Royal Veterinary College Equine Referral Hospital for investigation of left‐sided epistaxis, depression and gait abnormalities of approximately 1 month duration. Physical examination and cranial nerve evaluation were unremarkable. A small amount of haemorrhagic discharge was noted from the left nostril. Gait evaluation was suggestive of proprioceptive deficits. Computed tomography (CT) identified a mass lesion within the left conchofrontal and sphenopalatine sinuses extending through the cribriform plate into the calvarium. Histopathology of the mass revealed a neuroendocrine neoplasm, for which a diagnosis of esthesioneuroblastoma was favoured. This case highlights the usefulness of CT for the identification and extent of an intracranial mass and therefore its prognosis, however, histopathological examination was necessary to confirm the diagnosis.
Artificial electric field algorithm with repulsion mechanism
Authors: Zhang Gengfei , Cheng Jiatang
Published: August 2024

Due to its outstanding performance in addressing optimization problems, artificial electric field (AEF) algorithm has garnered increasing notice in recent years. Nevertheless, numerous studies indicate that AEF is susceptible to premature convergence when the region influenced by the global optimum constitutes a small fraction of the entire solution space. By conducting micro‐level research on the particles during the evolution process of AEF, it is revealed that the primary factors influencing optimization performance are the Coulomb's electrostatic force mechanism and the fixed attenuation factor. Inspired by this observation, we propose an improved version named artificial electric field algorithm with repulsion mechanism (RMAEF). Specifically, in RMAEF, a repulsion mechanism is incorporated to make particles escape from local optima. Furthermore, an adaptive attenuation factor is employed to update dynamically Coulomb's constant. RMAEF is compared with AEF and its state‐of‐art variants under 44 test functions from CEC 2005 and CEC 2014 test suites. From the experiment results, it is obvious that among 14 benchmark functions from CEC 2005 on 30D and 50D optimization, the RMAEF algorithm exhibits superior performance on 8 and 9 functions compared with advanced variants of AEF. For CEC 2014 on 30D and 50D optimization, the RMAEF algorithm produces the best results on 11 and 12 functions, respectively. In addition, three real‐world problems are also used to verify the versatility and robustness. The results demonstrate that RMAEF outperforms its competitors in terms of overall performance.
River flow intermittence influence biodiversity–stability relationships across spatial scales: Implications for an uncertain future
Authors: Gianuca Andros T. , di Cavalcanti Victor R. , Cruz Leonardo , Floury Mathieu , Crabot Julie , Valette Laurent , Piffady Jeremy , Datry Thibault
Published: August 2024

Climate change is increasing the proportion of river networks experiencing flow intermittence, which in turn reduces local diversity (i.e., α‐diversity) but enhances variation in species composition among sites (i.e., β‐diversity), with potential consequences on ecosystem stability. Indeed, the multiscale theory of stability proposes that regional stability can be attained not only by local processes but also by spatial asynchrony among sites. However, it is still unknown whether and how scale‐dependent changes in biodiversity associated with river flow intermittence influence stability across spatial scales. To elucidate this, we here focus on multiple metacommunities of French rivers experiencing contrasting levels of flow intermittence. We clearly show that the relative contribution of spatial asynchrony to regional stability was higher for metacommunities of intermittent than perennial rivers. Surprisingly, spatial asynchrony was mainly linked to asynchronous population dynamics among sites, but not to β‐diversity. This finding was robust for both truly aquatic macroinvertebrates and for taxa that disperse aerially during their adult stages, implying the need to conserve multiple sites across the landscape to attain regional stability in intermittent rivers. By contrast, metacommunities of truly aquatic macroinvertebrates inhabiting perennial rivers were mainly stabilized by local processes. Our study provides novel evidence that metacommunities of perennial and intermittent rivers are stabilized by contrasting processes operating at different spatial scales. We demonstrate that flow intermittence enhances spatial asynchrony among sites, thus resulting in a regional stabilizing effect on intermittent river networks. Considering that climate change is increasing the proportion of intermittent rivers worldwide, our results suggest that managers need to focus on the spatial dynamics of metacommunities more than on local‐scale processes to monitor, restore, and conserve freshwater biodiversity.
Optimistic growth of marginal region plantations under climate warming: Assessing divergent drought resilience
Authors: Li Jitang , Xie Yuyang , Camarero Jesús Julio , Gazol Antonio , González de Andrés Ester , Ying Lingxiao , Shen Zehao
Published: August 2024

Given the context of significant global warming and the intensification of extreme climate events in the last century, large‐scale reforestation and afforestation have been recognized as effective strategies to mitigate the climate crisis. Since the 1970s, China has launched several afforestation programs aimed at regional ecological protection, playing an important role in reaching carbon neutrality by 2060. This study provided a detailed analysis of the growth suitability of the main planted conifers (Pinus sylvestris var. mongolica and Pinus tabulaeformis) and broadleaves (Populus spp., Robinia pseudoacacia) in the semi‐arid northern China. We compared the radial growth trends of plantations and their responses to extreme droughts from 1980 to 2018. Growth of most plantations has significantly increased over time, but broadleaves showed recent growth reductions in the past decade, which may be related to tree age and reduced soil moisture. Nevertheless, under warmer climate scenarios, the growth of plantations is forecasted to continue increasing. Broadleaves showed a better post‐drought recovery, probably linked to their anisohydric behavior, than conifers, which presented a better resistance to drought. Growth of conifers depended more on warmer temperature and better precipitation conditions during the growing season, whereas broadleaves mainly reacted to warm temperature. Additionally, pre‐drought growth levels weakened resilience components, while post‐drought precipitation compensated for drought‐induced growth deficit. Growth and resilience were negatively related to tree age, while higher stand density reduced growth. This assessment and projections of growth and drought resilience indicate the sustainability of most plantations in semi‐arid regions, but future warmer and drier conditions may lead to an uncertain future regarding forest health and reduce their carbon sink potential.
Environment and microbiome drive different microbial traits and functions in the macroscale soil organic carbon cycle
Authors: Wasner Daniel , Schnecker Joerg , Han Xingguo , Sun Yifei , Frossard Aline , Zagal Venegas Erick , Boeckx Pascal , Doetterl Sebastian
Published: August 2024

Soil microbial traits and functions play a central role in soil organic carbon (SOC) dynamics. However, at the macroscale (regional to global) it is still unresolved whether (i) specific environmental attributes (e.g., climate, geology, soil types) or (ii) microbial community composition drive key microbial traits and functions directly. To address this knowledge gap, we used 33 grassland topsoils (0–10 cm) from a geoclimatic gradient in Chile. First, we incubated the soils for 1 week in favorable standardized conditions and quantified a wide range of soil microbial traits and functions such as microbial biomass carbon (MBC), enzyme kinetics, microbial respiration, growth rates as well as carbon use efficiency (CUE). Second, we characterized climatic and physicochemical properties as well as bacterial and fungal community composition of the soils. We then applied regression analysis to investigate how strongly the measured microbial traits and functions were linked with the environmental setting versus microbial community composition. We show that environmental attributes (predominantly the amount of soil organic matter) determined patterns of MBC along the gradient, which in turn explained microbial respiration and growth rates. However, respiration and growth normalized for MBC (i.e., specific respiration and growth) were more linked to microbial community composition than environmental attributes. Notably, both specific respiration and growth followed distinct trends and were related to different parts of the microbial community, which in turn resulted in strong effects on microbial CUE. We conclude that even at the macroscale, CUE is the result of physiologically decoupled aspects of microbial metabolism, which in turn is partially determined by microbial community composition. The environmental setting and microbial community composition affect different microbial traits and functions, and therefore both factors need to be considered in the context of macroscale SOC dynamics.
Clinical and immunoserological characteristics of anti‐p200 pemphigoid: Comparisons of patients with epitope spreading and non‐epitope spreading
Authors: Wang Yuan , Li Suo , Li Zhiliang , Jing Ke , Zhang Hanmei , Liang Guirong , Sun Chao , Qian Hua , Li Xiaoguang , Feng Suying
Published: August 2024

Background

Anti‐p200 pemphigoid is a rare autoimmune subepidermal blistering disease. Although the phenomenon of epitope spreading has been reported to be common in anti‐p200 pemphigoid, the association between its clinical and immunoserological features has yet to be elucidated.

Objectives

Our aim was to compare the clinical and immunoserological characteristics of anti‐p200 pemphigoid patients with and without epitope spreading.

Methods

We performed a retrospective cohort study encompassing 30 patients with anti‐p200 pemphigoid between January 2015 and December 2022. The clinical and immunoserological characteristics of anti‐p200 pemphigoid were analyzed using combined immunoserological assays.

Results

Epitope spreading was observed in 11 of 30 patients (36.7%) with anti‐p200 pemphigoid. Compared with patients in the non‐epitope spreading group, patients in the epitope spreading group showed more heterogeneous clinical presentations (P = 0.018), a higher proportion of mucosal involvement (P = 0.003), higher Bullous Pemphigoid Disease Area Index (BPDAI) scores for skin erosions/blisters (P = 0.018), mucosal erosions/blisters (P = 0.001), activity (P = 0.017) and total scores (P = 0.022), and required a higher initial dose of prednisone for disease control (P = 0.040).

Conclusions

This study supported the idea that anti‐p200 pemphigoid was prone to epitope spreading. Anti‐p200 pemphigoid patients with epitope spreading are more likely to present heterogeneous clinical phenotypes, frequent mucosal involvement, and a more severe and recalcitrant disease course.
Validation of the Peak Pruritus‐Numerical Rating Scale in patients with chronic plaque psoriasis: results from a phase 2 study
Authors: Draelos Zoe D. , Bushmakin Andrew G. , Ghosh Pranab , Xenakis Jason , Cappelleri Joseph C.
Published: August 2024

Background

Pruritus is a common, bothersome symptom for patients with mild‐to‐moderate plaque psoriasis (PsO), yet no validated scale assesses it in this patient population. We aimed to validate the Peak Pruritus‐Numerical Rating Scale (PP‐NRS) using data from a Phase 2b study investigating the efficacy of brepocitinib in patients with mild‐to‐moderate chronic PsO.

Methods

Patients completed the PP‐NRS daily from baseline for the first 2 weeks after the dose administration and subsequently only on visit days. Test–retest reliability (intraclass correlation coefficient [ICC]), construct validity (known group validity and convergent validity), ability to detect change, and meaningful within‐patient change (MWPC) were evaluated using correlation and regression analyses.

Results

The PP‐NRS demonstrated acceptable test–retest reliability (ICC: 0.86–0.89). Known‐group evidence demonstrated that PP‐NRS scores could discriminate between different degrees of disease severity. Convergent validity was supported by significant correlation coefficients between the PP‐NRS and Patient Global Assessment (PtGA), Dermatology Life Quality Index, and Psoriasis Symptom Inventory, which generally exceeded 0.50. The ability to detect change was evidenced by an approximately linear relationship between changes in PP‐NRS and Physician Global Assessment or PtGA of psoriasis scores. The value of 2.8 was determined as the MWPC for the PP‐NRS.

Conclusions

PP‐NRS is a reliable, practical test for assessing pruritus in mild‐to‐moderate PsO clinical trials.

ClinicalTrials.gov identifier

NCT03850483.
Living in LALA land? Forty years of attenuating Fc effector functions
Authors: Hale Geoff
Published: August 2024

The Fc region of antibodies is vital for most of their physiological functions, many of which are engaged through binding to a range of Fc receptors. However, these same interactions are not always helpful or wanted when therapeutic antibodies are directed against self‐antigens, and can sometimes cause catastrophic adverse reactions. Over the past 40 years, there have been intensive efforts to “silence” unwanted binding to Fc‐gamma receptors, resulting in at least 45 different variants which have entered clinical trials. One of the best known is “LALA” (L234A/L235A). However, neither this, nor most of the other variants in clinical use are completely silenced, and in addition, the biophysical properties of many of them are compromised. I review the development of different variants to see what we can learn from their biological properties and use in the clinic. With the rise of powerful new uses of antibody therapy such as bispecific T‐cell engagers, antibody‐drug conjugates, and checkpoint inhibitors, it is increasingly important to optimize the Fc region as well as the antibody binding site in order to achieve the best combination of safety and efficacy.
Accuracy of self‐reported treated hypertension in the women's health initiative: Comparisons with medication inventories
Authors: LaMonte Michael J. , Milton Grace M. , Miller Connor R. , Hovey Kathleen M. , Soliman Ahmed , Millen Amy E. , Wactawski‐Wende Jean
Published: August 2024

Few studies have reported on the accuracy of self‐reported hypertension history among older postmenopausal women, which was this study's objective. Participants were postmenopausal women enrolled in the Osteoporosis and Periodontal Disease (OsteoPerio) study, an ancillary investigation of the Women's Health Initiative Observational Study (WHI‐OS) at the Buffalo, New York, clinical site. Participants self‐reported their history of physician diagnosed hypertension treated with medication at WHI‐OS enrollment (1993–1998; n = 1342, mean age 63 years), then 3 years later at OsteoPerio enrollment (1997–2001; n = 1342), and again at OsteoPerio Year 5 follow‐up (2002–2005; n = 1020). At each time point, medication inventories were recorded and served as the criterion with which self‐report was compared in the present study. Physician diagnosed‐treated hypertension was also self‐reported annually on mailed health update questionnaires in the WHI‐OS and were compared against medication inventory at the subsequent clinic exam. Of those participants who self‐reported a history of hypertension at WHI enrollment, OsteoPerio enrollment, and OsteoPerio Year 5 follow‐up, 41.2%, 90.3%, and 94.4%, respectively, had anti‐hypertensive pills in their medication inventory. Across the three time points, sensitivity and specificity ranged from 0.72 to 0.98 and from 0.85 to 0.95, and kappa coefficients ranged from 0.52 to 0.79 when comparing self‐report with medication inventory. For self‐reported newly physician‐diagnosed and treated hypertension on the annual health update questionnaire, 88.4% and 95.2% of those reporting hypertension had anti‐hypertensive pills in the subsequent medication inventory. In general, sensitivity and kappa were lower in women aged ≥70 versus < 70 years and in those with history of cardiovascular disease and diabetes compared to those without these comorbidities. In this cohort of postmenopausal women, self‐reported physician diagnosed and treated hypertension demonstrated moderate to high accuracy when compared against anti‐hypertensive medication use documented by pill inventory, particularly for those who were younger and managing fewer comorbidities.
The evolving process of ferroptosis in thyroid cancer: Novel mechanisms and opportunities
Authors: Yin Lin , Luo Xiaodan , Zhang Xian , Cheng Bomin
Published: August 2024

Thyroid cancer (TC) is a prevalent endocrine malignancy, with a significant increase in incidence worldwide. Ferroptosis is a novel form of programmed cell death, primarily caused by iron overload and reactive oxygen species (ROS)‐dependent accumulation of lipid peroxides. The main manifestations of cellular ferroptosis are rupture of the outer membrane, crumpling of the mitochondria and shrinkage or disappearance of the mitochondrial cristae, thus leading to cell death. Ferroptosis is an important phenomenon in tumour progression, with crosstalk with tumour‐associated signalling pathways profoundly affecting tumour progression, immune effects and treatment outcomes. The functions and mechanisms of ferroptosis in TC have also attracted increasing attention, mainly in terms of influencing tumour proliferation, invasion, migration, immune response, therapeutic susceptibility and genetic susceptibility. However, at present, the tumour biology of the morphological, biological and mechanism pathways of ferroptosis is much less deep in TC than in other malignancies. Hence, in this review, we highlighted the emerging role of ferroptosis in TC progression, including the novel mechanisms and potential opportunities for diagnosis and treatment, as well as discussed the limitations and prospects. Ferroptosis‐based diagnostic and therapeutic strategies can potentially provide complementary management of TCs.
Langerhans cells: Central players in the pathophysiology of atopic dermatitis
Authors: Pan Yi , Hochgerner Mathias , Cichoń Małgorzata Anna , Benezeder Theresa , Bieber Thomas , Wolf Peter
Published: August 2024

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide. AD is a highly complex disease with different subtypes. Many elements of AD pathophysiology have been described, but if/how they interact with each other or which mechanisms are important in which patients is still unclear. Langerhans cells (LCs) are antigen‐presenting cells (APCs) in the epidermis. Depending on the context, they can act either pro‐ or anti‐inflammatory. Many different studies have investigated LCs in the context of AD and found them to be connected to all major mechanisms of AD pathophysiology. As APCs, LCs recruit other immune cells and shape the immune response, especially adaptive immunity via polarization of T cells. As sentinel cells, LCs are primary sensors of the skin microbiome and are important for the decision of immunity versus tolerance. LCs are also involved with the integrity of the skin barrier by influencing tight junctions. Finally, LCs are important cells in the neuro‐immune crosstalk in the skin. In this review, we provide an overview about the many different roles of LCs in AD. Understanding LCs might bring us closer to a more complete understanding of this highly complex disease. Potentially, modulating LCs might offer new options for targeted therapies for AD patients.