bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Classes and Early Health Inequalities in Comprehensive Schools in Finland
Authors: Kesanto‐Jokipolvi Heidi , Seppänen Piia , Koivuhovi Satu , Siipola Mari , Autio Reija , Rimpelä Arja
Published: July 2024

BACKGROUND

The origin of inequalities in health outcomes has been explained by health selection and social causation models. Health selection processes operate particularly at school age. We study, if student allocation to teaching groups with aptitude tests (selective vs general class) differentiates adolescents by health behaviors and mental health.

METHODS

Finnish schoolchildren 12‐13 years from 12 selective classes, n = 248; 41 general classes, n = 703 answered a questionnaire on addictive products (tobacco, snus, alcohol, and energy drinks), digital media use, and mental health (health complaints, anxiety, and depression). Structural equation modeling was conducted to identify structures between outcomes, SEP (socioeconomic position), class type, and academic performance.

RESULTS

Students in the selective classes reported less addictive digital media and addictive products use than students in the general classes. Differences in academic performance or SEP between the class types did not solely explain these differences. Mental health was not related to the class type. SEP was indirectly associated with health behaviors via the class type and academic performance.

CONCLUSIONS

Selecting students to permanent teaching groups with aptitude tests differentiates students according to risky health behaviors. The impact of education policies using student grouping should also be evaluated in terms of students' health.
Early progression during or after cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy indicates poor outcome with rescue protocols in dogs with multicentric lymphoma
Authors: Parker Ashley S. , Burton Jenna H. , Curran Kaitlin M. , Wolf‐Ringwall Amber , Thamm Douglas H.
Published: July 2024

Background

Dogs with lymphoma that fail cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (CHOP) before completion of their protocol are commonly thought to have poor long‐term outcome, but no previous studies have evaluated the effect of early relapse on progression‐free interval (PFI) or overall survival time (OST) for patients undergoing rescue chemotherapy.

Objective

Correlate rescue treatment outcomes in dogs with multicentric lymphoma with outcomes after 1st‐line CHOP chemotherapy.

Methods

Data were collected from 6 previous retrospective or prospective studies in 187 dogs with multicentric lymphoma that received 1st‐line CHOP chemotherapy and then received either lomustine (CCNU), L‐asparaginase and prednisone (LAP), or rabacfosadine (RAB, Tanovea), with or without prednisone or L‐asparaginase.

Results

The PFI after initiation of CHOP chemotherapy was significantly associated with response rate postprogression, PFI, and postrescue survival time (ST) for both rescue protocols. Immunophenotype (B‐ vs T‐cell) was not significantly associated with response, PFI or OST for LAP but was significantly associated with response and PFI for RAB.

Conclusion

Dogs that experience short PFI during or after 1st‐line CHOP chemotherapy had lower response rates to rescue treatment, with shorter PFI and ST. Immunophenotype did not significantly affect outcome with LAP but was associated with PFI for RAB.
Marital strain and emotional intimacy in midlife couples: The moderating role of empathy
Authors: Carasso Ella , Segel‐Karpas Dikla
Published: July 2024

Emotional intimacy is considered a fundamental factor contributing to the quality of marital relationships. However, marital strain can often limit intimacy. Thus, our first objective was to explore the intricate interplay between spouses' sense of intimacy and the levels of marital strain experienced by both themselves and their partners. In addition, the way partners respond to the challenges posed by marital strain can be pivotal in shaping the overall dynamics. Therefore, our second objective was to investigate whether and how the empathy exhibited by partners can protect the couple from the potential adverse effects of marital strain on emotional intimacy within the relationship. 96 midlife and older heterosexual couples reported on their sense of marital strain, emotional intimacy, and their level of empathy. We used Actor‐Partner Interdependence Model (APIM) to analyze the results. Negative associations were found between marital strain and emotional intimacy for both men and women. Men's empathy moderated the relationship between women's strain and intimacy, but women's empathy did not moderate the association between men's strain and intimacy. Assessing both spouses' strain is essential for understanding marital intimacy. Men's empathy can have a meaningful role in mitigating the experienced strain on marital outcomes.
Measuring positive LGBTQ+ identity: Psychometric properties of the Turkish Lesbian, Gay, and Bisexual Positive Identity Measure
Authors: Barburoğlu Yusuf , Çürükvelioğlu‐Köksal Eda , Özgülük Üçok S. Burcu , Gandhi Yuvamathi , Lannutti Pamela J. , Randall Ashley K.
Published: July 2024

Previous research with lesbian, gay, bisexual, transgender, queer, and various sexually and gender diverse (LGBTQ+) people has largely highlighted how experiences of discrimination and marginalization, and mental health outcomes are related. However, it is important that researchers operate from a strength‐based approach to identify how aspects of one's identity may foster resilience. It is crucial that people working with LGBTQ+ individuals have empirically supported and culturally verified measures to assess such constructs. In this regard, the Lesbian, Gay, and Bisexual Positive Identity Measure (LGB‐PIM) developed by Riggle et al. (2014) was aimed to be translated into Turkish, examining its psychometric properties and validity using a sample of 450 LGBTQ+ people from Turkey. Participants' mean age was 22.44 (SD = 4.61; range = 18–47) and most of them were educated. The five‐factor structure of the LGB‐PIM and its five subscales (authenticity, community, intimacy, self‐awareness, and social justice) was validated by the findings of confirmatory factor analyses. Future researchers may wish to use LGB‐PIM in studies that are designed to understand positive aspects among LGBTQ+ individuals such as resilience and coping and their associations with any type of close relationships (i.e., romantic relationships, friendships, family relations).
The functions of laccase gene GhLAC15 in fiber colouration and development in brown‐colored cotton
Authors: Jiao Junye , Zheng Hongli , Zhou Xinping , Huang Yinshuai , Niu Qingqing , Ke Liping , Tang Shouwu , Liu Haifeng , Sun Yuqiang
Published: July 2024

The monotonicity of color type in naturally colored cottons (NCCs) has become the main limiting factor to their widespread use, simultaneously coexisting with poor fiber quality. The synchronous improvement of fiber quality and color become more urgent and crucial as the demand for sustainable development increases. The homologous gene of wild cotton Gossypium stocksii LAC15 in G. hirsutum, GhLAC15, was also dominantly expressed in the developing fibers of brown cotton XC20 from 5 DPA (day post anthesis) to 25 DPA, especially at the secondary cell wall thickening stage (20 DPA and 25 DPA). In XC20 plants with downregulated GhLAC15 (GhLAC15i), a remarkable reduction in proanthocyanidins (PAs) and lignin contents was observed. Some of the key genes in the phenylpropane and flavonoid biosynthesis pathway were down‐regulated in GhLAC15i plants. Notably, the fiber length of GhLAC15i plants showed an obvious increase and the fiber color was lightened. Moreover, we found that the thickness of cotton fiber cell wall was decreased in GhLAC15i plants and the fiber surface became smoother compared to that of WT. Taken together, this study revealed that GhLAC15 played an important role in PAs and lignin biosynthesis in naturally colored cotton fibers. It might mediate fiber color and fiber quality by catalyzing PAs oxidation and lignin polymerization, ultimately regulating fiber colouration and development.
Garden of forking paths in ERP research – Effects of varying pre‐processing and analysis steps in an N400 experiment
Authors: Šoškić Anđela , Styles Suzy J. , Kappenman Emily S. , Ković Vanja
Published: July 2024

This study tackles the Garden of Forking Paths, as a challenge for replicability and reproducibility of ERP studies. Here, we applied a multiverse analysis to a sample ERP N400 dataset, donated by an independent research team. We analyzed this dataset using 14 pipelines selected to showcase the full range of methodological variability found in the N400 literature using systematic review approach. The selected pipelines were compared in depth by looking into statistical test outcomes, descriptive statistics, effect size, data quality, and statistical power. In this way we provide a worked example of how analytic flexibility can impact results in research fields with high dimensionality such as ERP, when analyzed using standard null‐hypothesis significance testing. Out of the methodological decisions that were varied, high‐pass filter cut‐off, artifact removal method, baseline duration, reference, measurement latency and locations, and amplitude measure (peak vs. mean) were all shown to affect at least some of the study outcome measures. Low‐pass filtering was the only step which did not notably influence any of these measures. This study shows that even some of the seemingly minor procedural deviations can influence the conclusions of an ERP study. We demonstrate the power of multiverse analysis in both identifying the most reliable effects in a given study, and for providing insights into consequences of methodological decisions.
Wetland restoration: can short‐term success criteria predict long‐term outcomes?
Authors: Adam Mathias , Cooper David J. , Jaunatre Renaud , Clément Jean‐Christophe , Gaucherand Stephanie
Published: July 2024

Worldwide wetland loss over the past 50 years has made wetland conservation a public policy priority, leading to an increase in wetland restoration programs. However, predicting long‐term restoration outcomes remains difficult. The monitoring of these programs rarely exceeds 5–10 years, forcing wetland managers to rely on short‐term success criteria that may be criticized by the scientific community. Our objective was to assess the significance of four short‐term success criteria (Carex ssp. shoot density, Salix ssp. survival, invasive species cover, and hydrologic dissimilarity to reference sites) used in a restoration program of 12 wetlands monitored for 5 years post‐restoration in predicting restoration outcomes 15 years post‐restoration. We defined the success of restoration efforts after 15 years using a cluster analysis‐based approach, and the clusters were described using principal coordinate analysis and Tukey's post hoc honest significant difference test. Finally, we assessed the pertinence of each short‐term success criteria in predicting long‐term restoration outcomes using Pearson correlation tests and spatial regressive models. Our results demonstrate that stress‐based short‐term success criteria can be reliable predictors of longer‐term success for communities with shallow water tables, whereas target‐species‐based short‐term success criteria are not. Hydrologic dissimilarity to the reference site was appropriate for willow‐sedge community outcome predictions, while invasive species cover was best for sedge community outcome predictions. For communities in drier habitats, such as the willow‐herb community, none of the tested short‐term success criteria were significant predictors of long‐term restoration outcomes, and further research is required to identify suitable short‐term success criteria.
Treatment of acute exacerbations of interstitial lung diseases with corticosteroids: Evidence?
Authors: Hung Chi F. , Raghu Ganesh
Published: July 2024

See related article
Estimation of win, loss probabilities, and win ratio based on right‐censored event data
Authors: Parner Erik T. , Overgaard Morten
Published: July 2024

The win ratio has in the recent decade gained popularity for analyzing prioritized multiple event data in clinical cohort studies, in particular within cardiovascular research. The literature on estimation of the win ratio using censored event data is however sparse. The methods that have been suggested have either an insufficient adjustment of the censoring or by assuming the the win and loss probabilities are proportional over time. The assumption of proportional win and loss probabilities will often in practice not be satisfied. In this paper, we present estimates for the win ratio, and win and loss probabilities, under independent right‐censoring and derive the asymptotic distribution of the estimates. The proposed win ratio estimate does not require the assumption of proportional win and loss probabilities. The small sample properties of the proposed method are studied in a simulation study showing that the variance formula is accurate even for small samples. The method is applied on two data sets.
Age‐related changes in cheek skin movement: A case study of Japanese women
Authors: Kurosumi Motonori , Yabuzaki Jiro , Kuribayashi Mari , Mizukoshi Koji
Published: July 2024

Background

The majority of conventional studies on skin aging have focused on static conditions. However, in daily life, the facial skin we encounter is constantly in motion due to conversational expressions and changes in facial expressions, causing the skin to alter its position and shape, resulting in a dynamic state. Consequently, it is hypothesized that characteristics of aging not apparent in static conditions may be present in the dynamic state of the skin. Therefore, this study investigates age‐related changes in dynamic skin characteristics associated with facial expression alterations.

Methods

A motion capture system measured the dynamic characteristics (delay and stretchiness of skin movement associated with expression) of the cheek skin in response to facial expressions among 86 Japanese women aged between 20 and 69 years.

Results

The findings revealed an increase in the delay of cheek skin response to facial expressions (r = 0.24, p < 0.05) and a decrease in the stretchiness of the lower cheek area with age (r = 0.60, p < 0.01). An increasing variance in delay and stretchiness within the same age group was also observed with aging.

Conclusion

The findings of this study revealed that skin aging encompasses both static characteristics, such as spots, wrinkles, and sagging, traditionally studied in aging research, and dynamic aging characteristics of the skin that emerge in response to facial expression changes. These dynamic aging characteristics could pave the way for the development of new methodologies in skin aging analysis and potentially improve our understanding and treatment of aging impressions that are visually perceptible in daily life but remain unexplored.
Evolution and host-specific adaptation ofPseudomonas aeruginosa
Authors: Weimann Aaron , Dinan Adam M. , Ruis Christopher , Bernut Audrey , Pont Stéphane , Brown Karen , Ryan Judy , Santos Lúcia , Ellison Louise , Ukor Emem , Pandurangan Arun P. , Krokowski Sina , Blundell Tom L. , Welch Martin , Blane Beth , Judge Kim , Bousfield Rachel , Brown Nicholas , Bryant Josephine M. , Kukavica-Ibrulj Irena , Rampioni Giordano , Leoni Livia , Harrison Patrick T. , Peacock Sharon J. , Thomson Nicholas R. , Gauthier Jeff , Fothergill Jo L. , Levesque Roger C. , Parkhill Julian , Floto R. Andres
Published: July 2024

The major human bacterial pathogenPseudomonas aeruginosacauses multidrug-resistant infections in people with underlying immunodeficiencies or structural lung diseases such as cystic fibrosis (CF). We show that a few environmental isolates, driven by horizontal gene acquisition, have become dominant epidemic clones that have sequentially emerged and spread through global transmission networks over the past 200 years. These clones demonstrate varying intrinsic propensities for infecting CF or non-CF individuals (linked to specific transcriptional changes enabling survival within macrophages); have undergone multiple rounds of convergent, host-specific adaptation; and have eventually lost their ability to transmit between different patient groups. Our findings thus explain the pathogenic evolution ofP. aeruginosaand highlight the importance of global surveillance and cross-infection prevention in averting the emergence of future epidemic clones.
A molecular glue degrader of the WIZ transcription factor for fetal hemoglobin induction
Authors: Ting Pamela Y. , Borikar Sneha , Kerrigan John Ryan , Thomsen Noel M. , Aghania Eamon , Hinman Amelia E. , Reyes Alejandro , Pizzato Nicolas , Fodor Barna D. , Wu Fabian , Belew Muluken S. , Mao Xiaohong , Wang Jian , Chitnis Shripad , Niu Wei , Hachey Amanda , Cobb Jennifer S. , Savage Nikolas A. , Burke Ashley , Paulk Joshiawa , Dovala Dustin , Lin James , Clifton Matthew C. , Ornelas Elizabeth , Ma Xiaolei , Ware Nathaniel F. , Sanchez Carina C. , Taraszka John , Terranova Remi , Knehr Judith , Altorfer Marc , Barnes S. Whitney , Beckwith Rohan E. J. , Solomon Jonathan M. , Dales Natalie A. , Patterson Andrew W. , Wagner Jürgen , Bouwmeester Tewis , Dranoff Glenn , Stevenson Susan C. , Bradner James E.
Published: July 2024

Sickle cell disease (SCD) is a prevalent, life-threatening condition attributable to a heritable mutation in β-hemoglobin. Therapeutic induction of fetal hemoglobin (HbF) can ameliorate disease complications and has been intently pursued. However, safe and effective small-molecule inducers of HbF remain elusive. We report the discovery of dWIZ-1 and dWIZ-2, molecular glue degraders of the WIZ transcription factor that robustly induce HbF in erythroblasts. Phenotypic screening of a cereblon (CRBN)–biased chemical library revealed WIZ as a previously unknown repressor of HbF. WIZ degradation is mediated by recruitment of WIZ(ZF7) to CRBN by dWIZ-1, as resolved by crystallography of the ternary complex. Pharmacological degradation of WIZ was well tolerated and induced HbF in humanized mice and cynomolgus monkeys. These findings establish WIZ degradation as a globally accessible therapeutic strategy for SCD.
An intron endonuclease facilitates interference competition between coinfecting viruses
Authors: Birkholz Erica A. , Morgan Chase J. , Laughlin Thomas G. , Lau Rebecca K. , Prichard Amy , Rangarajan Sahana , Meza Gabrielle N. , Lee Jina , Armbruster Emily , Suslov Sergey , Pogliano Kit , Meyer Justin R. , Villa Elizabeth , Corbett Kevin D. , Pogliano Joe
Published: July 2024

Introns containing homing endonucleases are widespread in nature and have long been assumed to be selfish elements that provide no benefit to the host organism. These genetic elements are common in viruses, but whether they confer a selective advantage is unclear. In this work, we studied intron-encoded homing endonuclease gp210 in bacteriophage ΦPA3 and found that it contributes to viral competition by interfering with the replication of a coinfecting phage, ΦKZ. We show that gp210 targets a specific sequence in ΦKZ, which prevents the assembly of progeny viruses. This work demonstrates how a homing endonuclease can be deployed in interference competition among viruses and provide a relative fitness advantage. Given the ubiquity of homing endonucleases, this selective advantage likely has widespread evolutionary implications in diverse plasmid and viral competition as well as virus-host interactions.
Can federal grid reforms solve the interconnection problem?
Authors: Armstrong Les , Canaan Alexa , Knittel Christopher , Metcalf Gilbert , Schittekatte Tim
Published: July 2024

Coordinated, comprehensive planning is sorely needed
Blockbuster T cells in the gut: A high-resolution view of immune modulation by the gut microbiome is presented
Authors: Nagashima Kazuki
Published: July 2024

A high-resolution view of immune modulation by the gut microbiome is presented
In Other Journals
Authors: Smith Keith T. , Jiang Di , Yeston Jake S. , Walia Ankit , Simonti Corinne N. , Lopez Bianca , Stajic Jelena
Published: July 2024

Editors’ selections from the current scientific literature
Transition from Super-Alfvénic to Sub-Alfvénic Stellar Wind Flow Passing by an Exoplanet, Using the Example of HD 209458b
Authors: Belenkaya E. S.
Published: July 2024

Depending on the distance of the exoplanet from the central star and the properties of this star, different regimes of stellar wind flow around it arise. If the exoplanet is located at a distance up to the Alfvén radius, where the wind speed is equal to the Alfvén speed, or the Alfvén Mach number $${{M}_{{\text{A}}}} = 1$$, the exoplanet generates Alfvén wings. If it is situated beyond the Alfvén radius, a comet-like magnetosphere appears, similar to that of the planets of the Solar System. The paper examines how the transition from one flow regime to another can be described on the base of a paraboloid model of the magnetospheric magnetic field using the example of exoplanet HD 209458b.
Efficacy of refrigerated gel packs for therapeutic hypothermia in neonatal retrieval: a retrospective cohort study
Authors: Morris Rachel , Harris Alex , Stewart Michael , Boland Rosemarie , Sett Arun
Published: July 2024

Objective

To determine the efficacy of refrigerated gel packs in achieving and maintaining target temperature in neonates receiving therapeutic hypothermia (TH) for hypoxic ischaemic encephalopathy during neonatal retrieval.

Design

Retrospective cohort study.

Setting

Paediatric Infant Perinatal Emergency Retrieval, Victoria, Australia.

Patients

200 neonates treated with TH during retrieval between 1 January 2015 and 31 December 2020.

Interventions

Active cooling with refrigerated gel packs or passive cooling.

Main outcome measures

The primary outcomes were the proportion of neonates who achieved therapeutic cooling rectal temperature (33–34°C) within 6 hours of birth and maintained target temperature range once TH was achieved. Secondary outcomes included need for respiratory support, inotropes, anticonvulsant therapy, sedation and survival at 7 days of life.

Results

200 neonates received TH. Median gestational age was 39 weeks and median birth weight 3300 g. 120 (60%) were actively cooled with refrigerated gel packs and the remainder passively cooled. 121 neonates (61%) reached target temperature within 6 hours and 14 (7%) after 6 hours of birth. Of those who achieved target temperature, 38% were maintained in therapeutic cooling range for the remainder of the retrieval.

Conclusions

Achieving and maintaining TH during neonatal retrieval with gel packs is challenging. Target temperature was not maintained in most neonates in this study. These findings support existing evidence favouring the use of servo-controlled cooling devices to optimise TH in the retrieval setting.
HAP-FAST: a feasibility study incorporating qualitative, mechanistic and costing sub-studies alongside a randomised pilot trial comparing chest x-ray to low-dose CT scan and empirical antibiotics to antibiotics guided by the BIOFIRE® FILM ARRAY® pneumoniapluspanel in adults with suspected non-ventilator-associated hospital-acquired pneumonia
Authors: Shafiqa Natalia , Aston Stephen , Howard Alex , Turtle Lance , Abrams Simon , Young Bridget , Sherratt Frances , Alvarez Nishio Anica , Willshaw Stephanie , Jones Ashley P , Wootton Dan G
Published: July 2024

Introduction

Non-ventilator-associated hospital-acquired pneumonia (nv-HAP) is the most common healthcare-associated infection (HCAI), is associated with high mortality and morbidity and places a major burden on healthcare systems. Diagnosis currently relies on chest x-rays to confirm pneumonia and sputum cultures to determine the microbiological cause. This approach leads to over-diagnosis of pneumonia, rarely identifies a causative pathogen and perpetuates unnecessary and imprecise antibiotic use. The HAP-FAST study aims to evaluate the feasibility of a randomised trial to evaluate the clinical impact of low-dose, non-contrast-enhanced thoracic CT scans and rapid molecular sputum analysis using the BIOFIRE® FILMARRAY® pneumoniapluspanel (FAPP) for patients suspected with nv-HAP.

Methods and analysis

The HAP-FAST feasibility study consists of a pilot randomised trial, a qualitative study, a costing analysis and exploratory analyses of clinical samples to investigate the immune-pathophysiology of HAP. Participants are identified and recruited from four acute hospitals in the Northwest of the UK. Using a Research Without Prior Consent model, the pilot trial will recruit 220 adult participants, with or without mental capacity, and with suspected HAP. HAP-FAST is a non-blinded, sequential, multiple assignment, randomised trial with two possible stages of randomisation: first, chest x-ray (CXR) or CT; second, if treated as nv-HAP, FAPP or standard microbiological processing alone (no FAPP). Pathogen-specific antibiotic guidance will be provided for FAPP results. Randomisation uses a web-based platform and followed up for 90 days. The feasibility of a future trial will be determined by assessing trial processes, outcome measures and patient and staff experiences.

Ethics and dissemination

This study has undergone combined review by the UK NHS Research Ethics Committee and Health Research Authority. Results will be disseminated via peer-reviewed journals, via the funders’ website and through a range of media to engage the public.

Trial registration number

NCT05483309.
Impact of isotype on the mechanism of action of agonist anti-OX40 antibodies in cancer: implications for therapeutic combinations
Authors: Willoughby Jane E , Dou Lang , Bhattacharya Sabyasachi , Jackson Heather , Seestaller-Wehr Laura , Kilian David , Bover Laura , Voo Kui S , Cox Kerry L , Murray Tom , John Mel , Shi Hong , Bojczuk Paul , Jing Junping , Niederer Heather , Shepherd Andrew J , Hook Laura , Hopley Stephanie , Inzhelevskaya Tatyana , Penfold Chris A , Mockridge C Ian , English Vikki , Brett Sara J , Srinivasan Roopa , Hopson Christopher , Smothers James , Hoos Axel , Paul Elaine , Martin Stephen L , Morley Peter J , Yanamandra Niranjan , Cragg Mark S
Published: July 2024

Background

OX40 has been widely studied as a target for immunotherapy with agonist antibodies taken forward into clinical trials for cancer where they are yet to show substantial efficacy. Here, we investigated potential mechanisms of action of anti-mouse (m) OX40 and anti-human (h) OX40 antibodies, including a clinically relevant monoclonal antibody (mAb) (GSK3174998) and evaluated how isotype can alter those mechanisms with the aim to develop improved antibodies for use in rational combination treatments for cancer.

Methods

Anti-mOX40 and anti-hOX40 mAbs were evaluated in a number of in vivo models, including an OT-I adoptive transfer immunization model in hOX40 knock-in (KI) mice and syngeneic tumor models. The impact of FcγR engagement was evaluated in hOX40 KI mice deficient for Fc gamma receptors (FcγR). Additionally, combination studies using anti-mouse programmed cell death protein-1 (mPD-1) were assessed. In vitro experiments using peripheral blood mononuclear cells (PBMCs) examining possible anti-hOX40 mAb mechanisms of action were also performed.

Results

Isotype variants of the clinically relevant mAb GSK3174998 showed immunomodulatory effects that differed in mechanism; mIgG1 mediated direct T-cell agonism while mIgG2a acted indirectly, likely through depletion of regulatory T cells (Tregs) via activating FcγRs. In both the OT-I and EG.7-OVA models, hIgG1 was the most effective human isotype, capable of acting both directly and through Treg depletion. The anti-hOX40 hIgG1 synergized with anti-mPD-1 to improve therapeutic outcomes in the EG.7-OVA model. Finally, in vitro assays with human peripheral blood mononuclear cells (hPBMCs), anti-hOX40 hIgG1 also showed the potential for T-cell stimulation and Treg depletion.

Conclusions

These findings underline the importance of understanding the role of isotype in the mechanism of action of therapeutic mAbs. As an hIgG1, the anti-hOX40 mAb can elicit multiple mechanisms of action that could aid or hinder therapeutic outcomes, dependent on the microenvironment. This should be considered when designing potential combinatorial partners and their FcγR requirements to achieve maximal benefit and improvement of patient outcomes.
Pass the tissue: restoring researcher access to legal human donations
Authors: Leston Meredith , De Lusignan Simon , Hobbs Richard Frederick
Published: July 2024

The sensitivity of human tissue and previous instances of misuse have, rightfully, led to the introduction of far-reaching oversight and regulatory mechanisms for accessing, storing and sharing samples. However, these restrictions, in tandem with more broad-based privacy regulations, have had the unintended consequence of obstructing legitimate requests for medical materials. This is of real detriment to ambitions for biomedical research, most notably the precision medicine agenda. As such, this paper makes the case for facilitating authorised researcher access to human tissue and associated data along practical medical ethics lines, detailing how liberating samples from unfit regulations, re-evaluating biobanks, diversifying considerations for donor benefit-risk, future proofing donor consent and flattening hierarchies of donation acceptability equate to a more cohesive and respectful means of managing biological samples and information than is achieved at present.
Predictors of a relapsing course in myelin oligodendrocyte glycoprotein antibody-associated disease
Authors: Virupakshaiah Akash , Schoeps Vinicius A , Race Jonathan , Waltz Michael , Sharayah Siefaddeen , Nasr Zahra , Moseley Carson E , Zamvil Scott S , Gaudioso Cristina , Schuette Allison , Casper Theron Charles , Rose John , Flanagan Eoin P , Rodriguez Moses , Tillema Jan-Mendelt , Chitnis Tanuja , Gorman Mark P , Graves Jennifer S , Benson Leslie A , Rensel Mary , Abrams Aaron , Krupp Lauren , Lotze Timothy E , Aaen Gregory , Wheeler Yolanda , Schreiner Teri , Waldman Amy , Chong Janet , Mar Soe , Waubant Emmanuelle
Published: July 2024

Background

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described demyelinating disorder, and children represent about 50% of all cases. Almost half of the patients experience relapses, but very few studies have evaluated predictors of relapse risk, challenging clinical management. The study aimed to identify predictors at MOGAD onset that are associated with a relapsing course.

Methods

Prospectively collected data from paediatric patients with MOGAD seen by the US Network of Paediatric MS Centres were leveraged. Univariable and adjusted multivariable models were used to predict recurrent disease.

Results

We identified 326 MOGAD cases (mean age at first event 8.9 years [SD 4.3], 57% female, 77% white and 74% non-Hispanic) and 46% relapsed during a mean follow-up of 3.9 years (SD 4.1). In the adjusted multivariable model, female sex (HR 1.66, 95% CI 1.17 to 2.36, p=0.004) and Hispanic/Latino ethnicity (HR 1.77, 95% CI 1.19 to 2.64, p=0.005) were associated with a higher risk of relapsing MOGAD. Maintenance treatment initiated before a second event with rituximab (HR 0.25, 95% CI 0.07 to 0.92, p=0.037) or intravenous immunoglobulin (IVIG) (HR 0.35, 95% CI 0.14 to 0.88, p=0.026) was associated with lower risk of a second event in multivariable analyses. Conversely, maintenance steroids were associated with a higher estimated relapse risk (HR 1.76, 95% CI 0.90 to 3.45, p=0.097).

Conclusion

Sex and ethnicity are associated with relapsing MOGAD. Use of rituximab or IVIG therapy shortly after onset is associated with a lower risk of the second event. Preventive treatment after a first event could be considered for those with a higher relapse risk.
Validation of self-reported male circumcision status and genital ulcer disease among Ugandan men
Authors: Galiwango Ronald Moses , Kigozi Godfrey , Feng Xinyi , Reynolds Steven , Quinn Thomas , Kiboneka Stephen Dalton , Mpagazi Josephine , Kereba John Baptist , Nakayijja Annet , Ssekubugu Robert , Chang Larry , Kagayi Joseph , Tobian Aaron , Grabowski Mary K
Published: July 2024

Objective

Voluntary medical male circumcision (MC) is a critical tool in combination HIV prevention programmes in Africa. Self-reported MC (SrMC) status is used in HIV epidemiological surveys to assess MC coverage but is subject to response bias with limited validation. This study evaluated the utility of SrMC status as a marker of MC as well as self-reported genital lesions for genital ulcer disease (GUD) among Ugandan men.

Methods

Male participants aged 18–49 years in the cross-sectional Sexually Transmitted Infection Prevalence study, conducted between May and October 2019, responded to a questionnaire capturing SrMC status and current genital ulcer symptoms followed by clinical assessment to verify MC and presence of GUD.

Sensitivity, specificity, positive predictive value, negative predictive value and corresponding CIs (95% CI) for SrMC status and GUD were estimated.

Results

There were 853 male participants, of whom 470 (55.1%) self-reported being circumcised and 23 (2.7%) self-reported GUD (SrGUD). MC was clinically confirmed in 50.2% (n=428) of participants with sensitivity of SrMC status at 99% (95% CI: 98% to 100%) and specificity 89% (95% CI: 86% to 92%). Specificity of SrMC was lowest among persons living with HIV and viremic (>1000 copies/mL) at 72% (95% CI: 46% to 90%). 18 participants had clinically confirmed GUD, but only 12 SrGUD symptoms, corresponding to a sensitivity and specificity of 67% (95% CI: 41% to 87%) and 99% (95% CI: 98% to 99%), respectively.

Conclusions

SrMC status is a robust proxy for clinically confirmed MC status and may reliably be used to assess MC coverage in this setting. Conversely, GUD symptoms were under-reported, which may impact effective syndromic management of sexually transmitted infections and warrants further examination.
Quality, acceptability and usability of self-sampling kits used by non-healthcare professionals for STI diagnosis in Spain: a single-blind study
Authors: Gómez-Castellá Javier , Cobos Briz Marta , Nuño Néstor , Diaz Asuncion , Bru-Gorraiz Francisco Javier , Martín-Gorgojo Alejandro , Almonacid-Garrido Maria Concepción , Mir Anna , Muñoz Mario , Del Amo Julia
Published: July 2024

Objectives

Sexually transmitted infections (STIs) have markedly increased over the last decade in Spain, calling for prevention and control innovative approaches. While there is evidence indicating the effectiveness of self-sampling for STI diagnosis, no kits for this purpose have been authorised in Spain.

Methods

A prospective single-blind cross-sectional study carried out between November and December 2022 in an STI clinic in Madrid, Spain, to determine the validity, feasibility and acceptability of self-sampling kits used by non-healthcare professionals from vagina, pharynx, rectum and urethra to diagnose
Chlamydia trachomatis
(CT) and
Neisseria gonorrhoeae
(NG). Self-samples were compared with samples collected by healthcare professional (HC samples) and analysed by PCR. Frequency of CT and NG diagnosis by sample type was compared using McNemar’s test for paired data. Sensitivity and specificity of self-samples for CT and NG diagnosis were also calculated.

Results

306 self-samples from 51 participants were analysed. 80% were men with median age of 33 (IQR: 28–38) years. Self-samples and HC samples showed no significant statistical differences in CT and NG diagnosis. Self-samples had a sensitivity of 81% for CT and 93% for NG, with a specificity of 97% for CT and 95% for NG. More than 90% of participants had no difficulty understanding the kit instructions and 71% expressed high levels of satisfaction with the self-sampling kit.

Conclusion

Self-sampling kits for CT and NG diagnosis can be safely and effectively used by non-healthcare professionals in Spain. National strategies for STI prevention and control should prioritise self-sampling strategies.
Antibiotic pharmacokinetics in infected pleural effusions
Authors: Arnold David T , Read Liam , Waddington Oliver , Hamilton Fergus W , Patole Sonia , Hughes Jessica , Milne Alice , Noel Alan , Bayliss Mark , Maskell Nicholas A , MacGowan Alasdair
Published: July 2024

Pleural infection is usually treated with empirical broad-spectrum antibiotics, but limited data exist on their penetrance into the infected pleural space. We performed a pharmacokinetic study analysing the concentration of five intravenous antibiotics across 146 separate time points in 35 patients (amoxicillin, metronidazole, piperacillin-tazobactam, clindamycin and cotrimoxazole). All antibiotics tested, apart from co-trimoxazole, reach pleural fluid levels equivalent to levels within the blood and well above the relevant minimum inhibitory concentrations. The results demonstrate that concerns about the penetration of commonly used antibiotics, apart from co-trimoxazole, into the infected pleural space are unfounded.
Differences in body condition and hepatic cellular metabolism among distinct populations of cestode-infected pumpkinseed sunfish (Lepomis gibbosus)
Authors: Sabbagh Sofia , Mélançon Vincent , Breton Sophie , Binning Sandra Ann
Published: July 2024

Host populations can vary in the prevalence and intensity of their parasites, which may influence the impacts of infection on host physiology and health. Parasite-induced effects on hosts may be due to underlying changes in cellular energy metabolism, predominantly driven by the mitochondria. However, limited research has been conducted on understanding variation in host–parasite interactions across populations. We sampled three wild populations of pumpkinseed sunfish ( Lepomis gibbosus (Linnaeus, 1758)), two of which are infected by cestodes, to study correlations among infection intensity, host body condition, and key metabolic enzyme activities in liver tissue. In both infected populations, cestode infection was associated with reduced hepatic lipid metabolism and increased hepatic lactic fermentation. Interestingly, Lake Cromwell fish showed a decrease in body condition, electron transport system activity, and antioxidant activity with cestode intensity, whereas the contrary was observed for Lake Long fish. This suggests that Lake Long fish could be boosting their immune system and food intake to better tolerate infection, unlike Cromwell fish. This study not only highlights how different populations can vary in their response to parasite infections but also the importance of accounting for infection when studying animal physiology.
Boundary spanners catalyze cultural and prescribed fire in western Canada
Authors: Hoffman Kira M. , Copes-Gerbitz Kelsey , Dickson-Hoyle Sarah , Bourbonnais Mathieu , Axelson Jodi , Cardinal Christianson Amy , Daniels Lori D. , Gray Robert W. , Holub Peter , Mauro Nicholas , Minocher Dinyar , Pascal Dave
Published: July 2024

Western Canada is increasingly experiencing impactful and complex wildfire seasons. In response, there are urgent calls to implement prescribed and cultural fire as a key solution to this complex challenge. Unfortunately, there has been limited investment in individuals and organizations that can navigate this complexity and work to implement collaborative solutions across physical, cognitive, and social boundaries. In the wildfire context, these boundaries manifest as jurisdictional silos, a lack of respect for certain forms of knowledge, and a disconnect between knowledge and practice. Here, we highlight the important role of “boundary spanners” in building trust, relationships, and capacity to enable collaboration, including through five case studies from western Canada. As individuals and organizations who actively work across and bridge boundaries between diverse actors and knowledge systems, we believe that boundary spanners can play a key role in supporting proactive wildfire management. Boundary spanning activities include: convening workshops, hosting joint training exercises, supporting knowledge exchange and communities of practice, and creating communication tools and resources. These activities can help overcome unevenly valued knowledge, lack of trust, and outdated policies. We need collaborative approaches to implement prescribed and cultural fire, including a strong foundation for the establishment of boundary spanning individuals and organizations.
Band gap generation in cantilever beams through periodic material removal
Authors: González Vania , Robin Olivier , Meruane Viviana
Published: July 2024

Traditional methods for generating band gaps in beams usually involve adding periodic elements like tuned mass dampers or masses, or applying complex geometrical changes. This research suggests a subtraction-based method achieved by removing material in the thickness direction through straightforward machining operations, thus forming periodic cells. The numerical studies start with band gap analysis, using periodic theory to assess different periodic cell configurations. This is followed by numerical and experimental studies on cantilever beams, each containing a set number of these periodic cells. Non-contact vibration measurements are conducted on one plain and six machined aluminum beams using a multipoint laser vibrometer and an automated impact hammer. The experimental findings corroborate the band gaps predicted by the numerical model, confirming the effectiveness of this approach. The study notes that the optimal periodicity of the cells and the contrast in thickness vary with the beam’s dimensions, and that the thickness contrast markedly affects the quantity, width, and intensity of the resulting band gaps. These results indicate that (1) periodic material removal in beam-like structures allows improved vibration reduction while mass is reduced, and (2) manufacturing can play a key role in vibration control in simple structures.
Driving voltage frequency and electrode material effects on electromagnetic radiation of the surface dielectric barrier discharge in the air
Authors: Pekárek Stanislav
Published: July 2024

The electrical discharges are, among others, accompanied by the emission of electromagnetic waves of various frequencies. We studied this emission for the surface dielectric barrier discharge in the air. We used the discharge with one strip-driven electrode and a sinusoidal driving voltage of frequencies 5 and 10 kHz. From the spectra of emitted waves in the frequency band up to 3 GHz, we found that this type of discharge emits the radiation of frequencies below 500 MHz. In this frequency band, we focused on the effect of the driving voltage frequency and driven electrode material on the spectra of these waves. It was found that emitted radiation is distributed in several packages of frequencies, and an increase in the driving voltage frequency or voltage increases the power level of emitted radiation. Compared with the radiation spectrum of the discharge with an aluminium-driven electrode in the spectrum of the discharge with the copper-driven electrode, new peaks of various power levels and the shift of certain radiation frequencies to lower values appear. To understand the underlying mechanism of the discharge electromagnetic waves emission, we focused on the correlation between the electric component of emitted EMWs and the discharge electrical parameters as a function of time and discharge voltage.

Graphical abstract
An intelligent solar-assisted 1kW Lithium–Bromide vapor absorption system
Authors: Lal Murari , Sadhu P. K. , Das Soumya
Published: July 2024

A ground-breaking solution that combines solar thermal energy and lithium-bromide vapor absorption technology to produce energy-efficient cooling and heating is the Intelligent Solar Assist 1[Formula: see text]kW Lithium Bromide Vapor Absorption system. This cutting-edge system uses the sun’s energy to power the absorption cycle, offering environmentally friendly and economically viable thermal management. Solar thermal collectors, a lithium bromide absorption chiller, a thermal energy storage device, and sophisticated control algorithms comprise the system’s main parts. Sunlight is captured and converted by solar thermal collectors into thermal energy, which is then used to produce the necessary heat for the lithium bromide absorption chiller. This chiller uses the absorption refrigeration cycle to efficiently cool or heat the specified area or process. When intelligent control algorithms are incorporated, the system performs and operates more effectively and efficiently. These algorithms regulate the thermal energy storage unit and optimize the use of solar energy, delivering a constant and dependable supply of cooling or heating as needed. Advanced monitoring and diagnostics features are also built into the system, allowing for remote control and in-the-moment performance evaluation. Disadvantages are ethical issues, lack of generalization, interpretability and complexity, scalability and processing resources, and scientific agreement. A novel Chimp-based recurrent model (CbRM) has been planned to be designed to predict the desired efficiency from the Evacuated Tube Collector (ETC) to overcome this issue. Comparing the Intelligent Solar Assist system to conventional heating and cooling systems, several benefits must be had. It minimizes greenhouse gas emissions, lessens reliance on traditional energy sources, and promotes a more sustainable future. The system also saves money using solar energy, lowering power costs and enhancing energy efficiency. Moreover, the proposed system implementation is done in Matlab. The method achieves the high efficiency of ETC in the range of about 0.9% which increases by 0.3% and the higher rate of COP was about 9.5% which increases up to 6%, as the increased concentration level of the strong solution was about 6.5% it was nearly 5% increase. The parameters in the suggested model were compared to the current parameters for the comparison analysis, and it was discovered that the proposed model had superior presenting efficiency.
Modelling transport pathways of faults with low hydraulic connectivity in mudstones with low swelling capacity
Authors: Ohno Hirokazu , Ishii Eiichi , Takeda Masaki
Published: July 2024

Faults in some deep mudstones have poor hydraulic connectivity owing to high normal stress on the fault planes. Designing a method for modelling solute transport pathways in such faults/fractures using available data is a critical issue vis-à-vis the safety assessment of radioactive waste disposal. In this study, faults in deep siliceous mudstones with low swelling capacity are investigated using cross-hole hydraulic and tracer tests between two boreholes. The water pressures observed during the hydraulic test are reproduced via hydraulic simulations, assuming a one-dimensional (1D) flow channel with a length 8–80 times the linear distance (4.5 m) between the two borehole test sections. This flow channel length indicates a tortuosity remarkably higher than that previously reported in discrete fracture network simulations and laboratory experiments using a single fracture (i.e. 1–5). Advection–dispersion simulations using a pipe model with a tortuosity of 8–80 reproduces a time series of tracer concentrations observed during the tracer test. The radius of the pipe simulated in the tracer test was 7–39 times the flow channel radius estimated via the hydraulic test, which is in agreement with the ratio of 5–20 previously reported based on
in situ
tracer and hydraulic tests of faulted/fractured rocks. The simulated longitudinal dispersivity is 1/9–1/20 of the estimated flow path lengths, in agreement with the laboratory and field tracer study values. These results indicate that transport pathways in faults with low hydraulic connectivity can be modelled using a highly tortuous 1D pipe flow path.