bluuebunny/crossref_metadata_2025 huggingface dataset:
In-vivo and in-silico studies to identify toxicity mechanisms of permethrin with the toxicity-reducing role of ginger
Authors: Himtaş Damla , Yalçin Emine , Çavuşoğlu Kültiğin , Acar Ali
Published: January 2024

In this study, the toxic effects of permethrin on Allium cepa L. and the protective role of Zingiber officinale rhizome extract (Zoex) were investigated. In this context, 6 different groups were formed. While the control group was treated with tap water, the groups II and III were treated with 10 µg/mL and 20 µg/mL Zoex, respectively, and the group IV was treated with 100 µg/L permethrin. The protective effect of Zoex against permethrin toxicity was studied as a function of dose, and groups V and VI formed for this purpose were treated with 10 µg/mL Zoex + 100 µg/L permethrin and 20 µg/mL Zoex + 100 µg/L permethrin, respectively. After 72 h of germination, cytogenetic, biochemical, physiological, and anatomical changes in meristematic cells of A. cepa were studied. As a result, permethrin application decreased the mitotic index (MI) and increased the frequency of micronuclei (MN), and chromosomal abnormalities. The increase in malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) and the decrease in glutathione (GSH) indicate that permethrin causes oxidative damage. Compared to the control group, a 68.5% decrease in root elongation (p < 0.05) and an 81.8% decrease (p < 0.05) in weight gain were observed in the permethrin-treated group. It was found that the application of Zoex together with permethrin resulted in regression of all detected abnormalities, reduction in the incidence of anatomical damage, MN and chromosomal aberrations, and improvement in MI rates. The most significant improvement was observed in group VI treated with 20 µg/mL Zoex, and Zoex was also found to provide dose-dependent protection. The toxicity mechanism of permethrin was also elucidated by molecular docking and spectral studies. From the data obtained during the study, it was found that permethrin has toxic effects on A. cepa, a non-target organism, while Zoex plays a protective role by reducing these effects.
Effekte von Teilqualifizierungen auf Beschäftigung und Einkommen
Authors: Kruppe Thomas , Lang Julia , Osiander Christopher
Published: January 2024

Teilqualifizierungen (auch: Teilqualifikationen) sind ein relativ neues Instrument im Instrumentenkasten der aktiven Arbeitsmarktpolitik in Deutschland. Sie bieten in ausgewählten Berufsfeldern die Möglichkeit, einzelne Bausteine beruflicher Qualifikation zu erwerben. Damit sollen sie die Arbeitsmarktchancen von formal gering Qualifizierten, d. h. von Personen ohne eine abgeschlossene Berufsausbildung, verbessern und es Teilnehmenden ermöglichen, schrittweise durch das Absolvieren einzelner Modulbausteine mittelfristig einen vollwertigen Berufsabschluss zu erwerben. Bislang ist allerdings noch wenig über die empirische Verbreitung, den konkreten Einsatz und die Wirkungen von Teilqualifizierungen bekannt. Deshalb untersucht dieser Beitrag mithilfe von administrativen Daten der Bundesagentur für Arbeit und eines statistischen Matching-Ansatzes, welche Effekte Teilqualifizierungen auf Beschäftigung und Einkommen haben. Empirisch zeigt sich, dass Teilnehmende häufig nur ein Teilqualifizierungsmodul von mehreren möglichen absolvieren. Vergleicht man Teilnehmende an diesen Teilqualifizierungen mit ähnlichen nichtteilnehmenden Arbeitslosen, so findet man Beschäftigungseffekte in der Größenordnung von zehn bis fast 15 Prozentpunkten, die inhaltlich bedeutsam und statistisch signifikant sind. Effekte auf das Einkommen der Teilnehmenden sind ebenfalls positiv und substanziell. Sie können durch höhere Löhne und bessere Beschäftigungschancen getrieben sein. In Berufsfeldern, in denen sowohl Teilqualifizierungen als auch Umschulungen gefördert werden, zeigen sich ähnlich hohe Beschäftigungseffekte für beide Maßnahmentypen. Umschulungen haben aber einen etwas größeren positiven Effekt auf das erzielte Einkommen.
Acupuncture Versus Oral Medications for Acute/Subacute Non-Specific Low Back Pain: A Systematic Review and Meta-Analysis
Authors: Lin Huize , Wang Xiang , Feng Yixuan , Liu Xiaoxu , Liu Lanping , Zhu Kexin , Shen Jianghong , Zhang Pingping , Yu Jinna , Yang Tao
Published: January 2024

Purpose of Review

Pharmacologic intervention do not always achieve benefits in the treatment of acute/subacute non-specific low back pain (NSLBP). We assessed efficacy and safety of acupuncture for acute/subacute NSLBP as alternative treatment.

Recent Findings

We searched PubMed, Web of Science, Embase, Cochrane Library, Scopus, Epistemonikos, CNKI, Wan Fang Database, VIP database, CBMLD, CSTJ, clinical trials, EUCTR, World WHO ICTRP, and ChiCTR for randomized controlled trials, cross-over studies, and cohort studies of NSLBP treated by acupuncture versus oral medication from inception to 23th April 2022. A total of 6 784 records were identified, and 14 studies were included 1 263 participants in this review. The results of the meta-analysis indicated that acupuncture therapy was slightly more effective than oral medication in improving pain (P < 0.00001, I2 = 92%, MD = −1.17, 95% CI [−1.61, −0.72]). According to the results of the meta-analysis, acupuncture therapy exhibited a significant advantage over oral medication with a substantial effect (P < 0.00001, I2 = 90%, SMD = −1.42, 95% CI [−2.22, −0.62]). Based on the results of the meta-analysis, acupuncture therapy was associated with a 12% improvement rate compared to oral medication in patients with acute/subacute NSLBP (P < 0.0001, I2 = 54%, RR = 1.11, 95% CI [1.05, 1.18]).

Acupuncture is more effective and safer than oral medication in treating acute/subacute NSLBP. This systematic review is poised to offer valuable guidance to clinicians treating acute/subacute NSLBP and potentially benefit the afflicted patients.

Registration

This review was registered in PROSPERO (http://www.crd.york.ac.uk/prospero) with registration number CRD42021278346.
Why do low spirits last? Investigating correlates of cumulative unhappiness using German panel data
Authors: Bittmann Felix
Published: January 2024

Experiencing states of unhappiness is normal and part of human existence. Yet, if these states occur often or for longer periods of time, this can become a large burden and greatly reduce a person’s overall quality of life. I refer to these states as cumulative unhappiness, and I empirically investigated which factors and variables are correlated with them. Using large-scale German panel data (N = 8,646; mean age = 51.7 years, SD = 10.7 years), I attempted to model the correlates of cumulative unhappiness over a period of nine years and included factors such as sociodemographic-background variables, social origin, education, income, household situation, social capital, personality traits, unemployment, and health. Bivariate analyses indicated that health and household income are the two most relevant predictors of unhappiness. In multivariate modeling using dominance analysis, I demonstrated that about 26% of the total variation of cumulative unhappiness can be explained by all independent variables together. In these analyses, the most relevant influential factors were health (14.8%), social status and income (4.0%), and social capital (3.1%). These results indicate that cumulative unhappiness can be explained to some extent.
A contribution to the urbanization and marble supply of Roman Thrace: an interdisciplinary study
Authors: Andreeva Petya , Anevlavi Vasiliki , Frerix Benjamin , Cenati Chiara , Prochaska Walter , Ladstätter Sabine , Karadimitrova Krasimira
Published: January 2024

The study of marble trade in antiquity has received a lot of scholarly attention in the last few decades; however, numerous deposits of high-quality white marble in the Thracian interior have only recently become pivotal in Bulgaria. Following the establishment of Thrace as a Roman province, investments into transport infrastructure, urban and rural construction works and monumentalizing architecture in marble have led to an increased demand for stone. Local marble quarries close to urban centres and larger imperial quarries were used for civic buildings, villas and sanctuaries. Provenance analysis of marble quarries and artefacts has established a close link between the place of origin and subsequent place of use. This multi-disciplinary study explores marble sources in the Thracian interior via various approaches such as epigraphy, archaeology, and archaeometry regarding urbanization, trade, and transportation. In this paper, we consider and investigate the Berkovitsa marble, a quarry close to Montana in northwestern Bulgaria, and present a broader framework for the marble trade of the region.
Older LGBT+ Adults and Physical Activity: A Systematic Review of Qualitative and Quantitative Data
Authors: Pistella Jessica , Baiocco Roberto , Antoniucci Chiara , Alessandri Guido , Alivernini Fabio , Borghi Anna M. , Filosa Lorenzo , Fini Chiara , Palombi Tommaso , Tavolucci Simone , Lucidi Fabio
Published: January 2024

Introduction

The present study represents the first systematic review summarizing existing publications on older sexual and gender minority (LGBT+) people's engagement with physical activity (PA) aged 65 and over.

Methods

Relevant articles were systematically searched in four scientific databases (i.e., PsychArticles, PsychInfo, Pubmed, and Web of Science) in March 2023. We included original articles published after 1968 with relevant keywords associated with “PA”, “older adults”, and “LGBT+ identity”. Of the 887 records identified, 53 articles were included in the systematic review.

Results

Studies were critically reviewed according to participants’ subjectivity considered in the publications: (a) sexual minority (LGB+) identities; (b) sexual and gender minority (LGBT+) identities; (c) transgender and gender-diverse identities; (d) gay and bisexual male identities; and (e) lesbian and bisexual female identities. The most frequent research areas, taking together all the five identity categories considered in the present review, were the differences between LGBT+ people and cis-heterosexual people, the discrimination and homophobia/transphobia in sport-related contexts, and the competent interventions and aging well in LGBT+ older adults.

Conclusions

Findings suggest a lack of information regarding PA in older LGBT+ aged 65 and over. Future research should investigate the barriers and enablers of PA in older LGBT+ people.

Policy Implications

It is mandatory to promote regular exercise to reduce health disparities between older LGBT+ individuals and their cis-heterosexual counterparts. The policy and environmental implications of the findings for older LGBT+ people are discussed.
Numerical simulation study on impact factors to dynamic filtration loss
Authors: Kong Cuilong , Sun Yuxue , Li Chengli , Zhao Jingyuan , Zhu Xiuyu
Published: January 2024

During drilling operations, naturally, fractured formations are prone to show serious mud losses, which hinder drilling and increase nonproductive time and costs. The influencing factors of dynamic fluid loss are important for optimizing drilling parameters, reducing drilling fluid loss, and protecting oil and gas reservoirs. In this study, we simulated the dynamic filtration loss of drilling fluid during drilling under formation conditions using commercial software CMG (Computer Modelling Group). The effects of filtration time, filtrate viscosity, pressure difference, internal filter cake permeability, and external filter cake permeability on filtration loss were investigated. The simulation results showed that the permeability of the external mud cake is an important factor to control the fluid loss, and the pressure consumed by the external mud cake with low permeability can account for more than 90% of the total pressure difference. When the permeability of the external mud cake is high, the permeability of the internal mud cake also has a significant influence on the dynamic fluid loss. Under formation conditions, the dynamic fluid loss of radial fluid loss is still proportional to the filtration time and pressure difference, and inversely proportional to the filtrate viscosity of drilling fluid. Under the simulated conditions, the pressure will quickly transfer to the boundary, and the formation pressure at the same position in the formation will gradually increase, while the increase is relatively small with a constant filtration rate. The results of this paper can be used to the real site for drilling optimization. This numerical analysis method can be easily applied to filtrate loss analysis, formation damage area calculation, and other radial flow-related study.
Thermal Tolerance of the Shallow-Water Ostracod Cyprideis from a Lagoon in Bahrain, Western Arabian Gulf
Authors: Prayudi Sinatrya Diko , Korin Asmaa , Kaminski Michael A.
Published: January 2024

Laboratory experiments were conducted to determine the thermal tolerance of the living ostracod Cyprideis sp. from a lagoon known as Murray’s Pool on the east coast of Bahrain, in the western Arabian Gulf. Our experimental trials, run in duplicate using a semi-controlled thermal incubator, demonstrate the resilience of the ostracod community to elevated temperatures. We observed that ostracod specimens begin to enter an inactive condition or become comatose at about 39.4 °C, and with increase in temperatures, half of the specimens died or did not recover at 51.8 °C. At 53.5 °C, total mortality is observed with no indication of recovery. These observations have implications for climate change predictions in the western Gulf region, as water temperatures in the lagoon reach 42 °C in summer, while the substrate temperatures on mud flats exposed during low tide exceed the lethal limit of the ostracods during the summer months.
Understanding and responsiveness in the trauma-informed adult ESL classroom
Authors: Wilson Victoria E. , Le Brocque Robyne , Drayton John , Hammer Sara
Published: January 2024

This paper reports the findings of a critical qualitative study on trauma-informed teaching of English as a second language (ESL) at Australian universities. Post-traumatic stress affects verbal learning, yet most ESL teachers do not receive training in trauma-informed teaching. The field has suffered from a dearth of empirical studies and absence of student voice. This study used a validated tool to measure the post-traumatic stress of 39 participants, including international students and former refugees. Twenty of these completed semi-structured interviews about the ESL learning environment, based on a framework of trauma-informed principles. Data were analysed using critical, qualitative methods through a trauma-informed lens. A major theme in the findings was the importance of ESL teachers’ understanding of students. Within this theme, four sub-themes are explored: personal engagement and attention, acceptance and understanding of the learner role, understanding the lives of students outside the classroom and an understanding of students’ cultures.
Modulation of mitochondrial activity by sugarcane (Saccharum officinarum L.) top extract and its bioactive polyphenols: a comprehensive transcriptomics analysis in C2C12 myotubes and HepG2 hepatocytes
Authors: Iwata Kengo , Ferdousi Farhana , Arai Yoshinobu , Isoda Hiroko
Published: January 2024

Age-related mitochondrial dysfunction leads to defects in cellular energy metabolism and oxidative stress defense systems, which can contribute to tissue damage and disease development. Among the key regulators responsible for mitochondrial quality control, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is an important target for mitochondrial dysfunction. We have previously reported that bioactive polyphenols extracted from sugarcane top (ST) ethanol extract (STEE) could activate neuronal energy metabolism and increase astrocyte PGC-1α transcript levels. However, their potential impact on the mitochondria activity in muscle and liver cells has not yet been investigated. To address this gap, our current study examined the effects of STEE and its polyphenols on cultured myotubes and hepatocytes in vitro. Rhodamine 123 assay revealed that the treatment with STEE and its polyphenols resulted in an increase in mitochondrial membrane potential in C2C12 myotubes. Furthermore, a comprehensive examination of gene expression patterns through transcriptome-wide microarray analysis indicated that STEE altered gene expressions related to mitochondrial functions, fatty acid metabolism, inflammatory cytokines, mitogen-activated protein kinase (MAPK) signaling, and cAMP signaling in both C2C12 myotubes and HepG2 hepatocytes. Additionally, protein–protein interaction analysis identified the PGC-1α interactive-transcription factors-targeted regulatory network of the genes regulated by STEE, and the quantitative polymerase chain reaction results confirmed that STEE and its polyphenols upregulated the transcript levels of PGC-1α in both C2C12 and HepG2 cells. These findings collectively suggest the potential beneficial effects of STEE on muscle and liver tissues and offer novel insights into the potential nutraceutical applications of this material.

Graphical Abstract
A Generalized Accelerated Failure Time Model to Predict Restoration Time from Power Outages
Authors: Jamal Tasnuba Binte , Hasan Samiul
Published: January 2024

Major disasters such as wildfire, tornado, hurricane, tropical storm, and flooding cause disruptions in infrastructure systems such as power and water supply, wastewater management, telecommunication, and transportation facilities. Disruptions in electricity infrastructure have negative impacts on sectors throughout a region, including education, medical services, financial services, and recreation. In this study, we introduced a novel approach to investigate the factors that can be associated with longer restoration time of power service after a hurricane. Considering restoration time as the dependent variable and using a comprehensive set of county-level data, we estimated a generalized accelerated failure time (GAFT) model that accounts for spatial dependence among observations for time to event data. The model fit improved by 12% after considering the effects of spatial correlation in time to event data. Using the GAFT model and Hurricane Irma’s impact on Florida as a case study, we examined: (1) differences in electric power outages and restoration rates among different types of power companies—investor-owned power companies, rural and municipal cooperatives; (2) the relationship between the duration of power outage and power system variables; and (3) the relationship between the duration of power outage and socioeconomic attributes. The findings of this study indicate that counties with a higher percentage of customers served by investor-owned electric companies and lower median household income faced power outage for a longer time. This study identified the key factors to predict restoration time of hurricane-induced power outages, allowing disaster management agencies to adopt strategies required for restoration process.
Effect of core stabilization versus rebound therapy on balance in children with cerebral palsy
Authors: AL-Nemr Alaa , Kora Alaa Noureldeen
Published: January 2024

Objective

This study aimed to compare the effect of core stabilization exercises and rebound therapy on balance in children with hemiplegic cerebral palsy (CP).

Methods

Fifty- two children of spastic hemiplegic CP aged 5 up to 8 years from both genders were assigned randomly into two groups: core stability and rebound therapy groups. Both groups received 3 sessions/week, 1.5-h training per session, for 12 successive weeks. The measurement was performed at baseline and post-treatment. Balance as a primary outcome for this study was measured by a Biodex Balance System (BBS), and knee extensor strength and functional capacity as secondary outcomes were assessed using a hand-held dynamometer, and a six-minute walk test (6MWT), respectively.

Results

All variables showed a significant improvement after intervention in each group (p < 0.0001), with significant improvement in all stability indices (overall, anteroposterior, and mediolateral) in core stability group when compared to rebound therapy group.

Conclusion

Core stability exercises and rebound therapy are recommended in the rehabilitation of children with hemiplegic CP. Core stability exercises were more effective than rebound therapy for balance improvement.

Trial registration number

NCT05739396.
Performance evaluation of a dual-chamber plant microbial fuel cell developed for electricity generation and wastewater treatment
Authors: Golzarian M. , Ghiasvand M. , Shokri S. , Bahreini M. , Kazemi F.
Published: January 2024

Plant microbial fuel cells (PMFC) have attracted great scholarly attention as a renewable energy source. These cells have three main components: anode, cathode chambers, and a proton exchange membrane. In this study, a dual-chamber plant microbial fuel cell system was designed using Cyperus papyrus and Shewanella oneidensis. The effects of various factors, including the size of the electrodes, the distance between the electrodes, and the inoculation volume of Shewanella oneidensis, on the ability of electricity generation, were scrutinized. The results indicated that increasing the size area of the electrodes from 2 × 2 to 4 × 4 and 6 × 6 cm2 caused an increase in the output voltage by 43% and 58%, respectively. The PMFC produced a maximum power of 240 mW, with a Coulombic efficiency ranging from 0.66 to 0.75%. The plant microbial fuel cell designed in this study seemed to have a high potential to remove wastewater contaminants. Based on the results, during five days of setting up the system, COD and BOD decreased by 61.75% and 93.16%, respectively, which shows that in addition to generating power, the designed PMFC had a high potential to remove wastewater contaminants.
Implantation of Adipose-Derived Mesenchymal Stromal Cells (ADSCs)-Lining Prosthetic Graft Promotes Vascular Regeneration in Monkeys and Pigs
Authors: Zuo Xiao , Han Pengfei , Yuan Ding , Xiao Ying , Huang Yushi , Li Rui , Jiang Xia , Feng Li , Li Yijun , Zhang Yaya , Zhu Ping , Wang Hongge , Wang Ning , Kang Y. James
Published: January 2024

Background:

Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem.

Method:

We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys.

Results:

Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome.

Conclusion:

This cell-based vascular graft is ready to undergo clinical trials for human patients.
Barriers and Facilitators of Healthcare Access for Autistic Children in the UK: a Systematic Review
Authors: Babalola Tonia , Sanguedolce Giulia , Dipper Lucy , Botting Nicola
Published: January 2024

Background

Individuals with autism are more likely to suffer from various physical and mental health problems and experience disparities in effectively accessing healthcare services. This review aims to identify studies that report on the experiences of autistic children, their parents/carers, and the healthcare professionals treating them; to develop an understanding of the facilitators and barriers to healthcare access in order to inform policies and practice to improve access to healthcare for autistic children in the UK.

Methods

A total of 3069 records were screened, and 24 studies were included; six quantitative, four qualitative, and fourteen mixed-methodology studies.

Results

Professional and parental knowledge about autism, sensory issues, challenging behaviour, system-level barriers, patient-provider-parent communication issues, lack of person-centred care, stigma, and culture emerged as significant barriers to accessing healthcare for autistic children.

Conclusions

Families of autistic children experience several barriers to accessing healthcare. Recommendations for those planning services and clinicians are discussed.
Variables that explain disordered eating behaviors among women: the mediating role of body dissatisfaction
Authors: Franco-Paredes Karina , Díaz-Reséndiz Felipe J. , Peláez-Fernández María Angeles , Bautista-Díaz María Leticia
Published: January 2024

Purpose

To analyze the role of body dissatisfaction in the relationships of sociocultural influences, depression, and anxiety with disordered eating behaviors (DEB) in a sample of female Mexican university students.

Methods

A nonrandom sample of 526 female Mexican university students aged 18 to 25 years completed the Questionnaire of Influence on the Aesthetic Model of Body Shape (CIMEC-26), the Hospital Anxiety and Depression Scale (HADS), the Body Shape Questionnaire (BSQ-8D) and the Eating Attitudes Test (EAT-26).

Results

Through the mean model (χ2/df (5, n = 526) = 7.298, p = .199; NFI = .996; CFI = .999; RMSEA = .030; SRMR = .011), body dissatisfaction was found to mediate the relationships of influence of advertising, influence of social models and anxiety with DEB (restrictive dieting and bulimia). The variable with the most direct effect on restrictive dieting and bulimia was the influence of advertising. Body dissatisfaction partially mediated this relationship, as the influence of advertising had a significant direct effect on restrictive dieting and bulimia. The final model of direct and indirect effects explained 43% and 22% of the variance in restrictive dieting and bulimia, respectively.

Conclusion

The present study showed that body dissatisfaction partially mediated the relationships between influence of advertising, influence of social models, and anxiety with DEB among women. Thus, these variables should be taken into account in prevention and intervention programs targeting BED. Level V: Evidence obtained from a cross-sectional descriptive study.

Level V

Evidence obtained from a cross-sectional descriptive study.
Foramen ovale as a new determinative sign for the identification of tiger (Panthera tigris) and lion (Panthera leo) skulls
Authors: Formanova Dominika , Pyszko Martin , Horak Ondrej , Sadkova Jolana , Rihova Pavla , Kubatova Anna
Published: January 2024

Tiger and lion bones are valued highly on the wildlife black market. The skeletons of the two species are very similar, but the level of protection and the laws applicable to them differ. When detecting crime in the field, it can be crucial to recognize the skeletons of these two species by their morphological features. A distinguishing feature neglected in practice is the foramen ovale at the base of the skull. A total of 112 skulls were evaluated (55 tigers and 57 lions). The orientation and appearance of the foramina ovalia were analyzed on skull photographs. Significant differences were found between tigers and lions. In lions, the foramina ovalia faced laterally and their outlets were usually at least partially hidden behind the straight edge of the os basisphenoidale from the ventral view of the skull. In most adult tigers, the foramina ovalia faced more rostrally with their outlets visible and bounded by a semi-circular edge of the os basisphenoidale. However, tiger skulls exhibited higher variability in foramina ovalia orientation than lion skulls. Like other identifying features on tiger and lion skulls, the foramen ovale was unable to distinguish all skulls with 100% confidence. Nevertheless, knowledge of this structure can help considerably in species identification.
US FDA’s Dose Optimization Postmarketing Requirements and Commitments of Oncology Approvals and the Impact on Product Labels from 2010 to 2022: An Emerging Landscape from Traditional to Novel Therapies
Authors: Gendy Joseph M. , Nomura Naomi , Stuart Jeffrey N. , Blumenthal Gideon
Published: January 2024

Background

Dose optimization is a focal point of many US Food and Drug Administration (FDA) drug approvals. We sought to understand the impact of the FDA’s Postmarketing Commitments/Postmarketing Requirements (PMCs/PMRs) on dose optimization and prescriber labeling for oncology drugs.

Methods

Publicly available information was aggregated for all FDA oncology drug approvals between January 1, 2010, and December 31, 2022. Study completion dates were compared to product labeling before and after PMC/PMR fulfillment dates to evaluate labeling changes associated with dose-related PMCs/PMRs. Data were analyzed individually (2010–2015 and 2016–2022) due to differences in available information.

Results

From 2010 to 2015, 14 of 42 (33.3%) new molecular entities (NMEs) had dose-related PMCs/PMRs, with 6 of 14 (42.9%) resulting in a relevant label change. From 2016 to 2022, of the 314 new or supplemental applications approved, 21 had dose-related PMCs/PMRs (6.7%), which trended upward over time; 71.4% of dose-related PMCs/PMRs were NMEs. Kinase inhibitors (KIs) and antibody/peptide drug conjugates (ADCs/PDCs) were the most affected drug classes. Ten of the 21 approvals with dose-related PMCs/PMRs fulfilled their dosing PMCs/PMRs, and 3 of the 10 (30%) had relevant label changes.

Conclusion

Most dose-related PMRs/PMCs were issued for NMEs. Of these, KIs and ADCs/PDCs were highly represented, reflecting their novelty and greater uncertainty around their safety profile. PMC/PMR issuance broadly increased over time. With the implementation of the FDA’s Project Optimus in 2021, it remains to be seen whether fewer dose-related PMCs/PMRs emerge in future due to enhanced dose optimization in the premarketing setting.
ECS: an interactive tool for data quality assurance
Authors: Sieberichs Christian , Geerkens Simon , Braun Alexander , Waschulzik Thomas
Published: January 2024

With the increasing capabilities of machine learning systems and their potential use in safety-critical systems, ensuring high-quality data is becoming increasingly important. In this paper, we present a novel approach for the assurance of data quality. For this purpose, the mathematical basics are first discussed and the approach is presented using multiple examples. This results in the detection of data points with potentially harmful properties for the use in safety-critical systems.
Assessing systematic weaknesses of DNNs using counterfactuals
Authors: Gannamaneni Sujan Sai , Mock Michael , Akila Maram
Published: January 2024

With the advancement of DNNs into safety-critical applications, testing approaches for such models have gained more attention. A current direction is the search for and identification of systematic weaknesses that put safety assumptions based on average performance values at risk. Such weaknesses can take on the form of (semantically coherent) subsets or areas in the input space where a DNN performs systematically worse than its expected average. However, it is non-trivial to attribute the reason for such observed low performances to the specific semantic features that describe the subset. For instance, inhomogeneities within the data w.r.t. other (non-considered) attributes might distort results. However, taking into account all (available) attributes and their interaction is often computationally highly expensive. Inspired by counterfactual explanations, we propose an effective and computationally cheap algorithm to validate the semantic attribution of existing subsets, i.e., to check whether the identified attribute is likely to have caused the degraded performance. We demonstrate this approach on an example from the autonomous driving domain using highly annotated simulated data, where we show for a semantic segmentation model that (i) performance differences among the different pedestrian assets exist, but (ii) only in some cases is the asset type itself the reason for this reduction in the performance.
Preparation of high-performance manganese-based pseudocapacitor material by using spent lithium-ion battery anode graphite via mechanochemical pretreatment
Authors: Dai Lujie , Li Bang , Li Jia , Xu Zhenming
Published: January 2024

The potential for recycling graphitic carbon from lithium-ion battery (LIB) anodes has been overlooked due to its relatively low economic value in applications. This study proposed to use graphene nanoplates (GNPs), which were obtained from spent lithium battery anode graphite, treated with ball-milling method, for hydrothermal synthesis of MnO2-supported graphene nanoplates (MnO2/GNPs) composites materials. The composites exhibited excellent electrochemical characterization curves, indicating ideal capacitance characteristics. The analysis of MG24-20 material showed the good impact resistance and capacity retention around 100% with capacitance of 124.6F/g at 10 mV/s, surpassed similar samples using precious metals and high-end materials, enabling the reuse of spent graphite in energy conversion and storage system for effective utility.

Graphical Abstract
Life-Course Socioeconomic Position and Mild Cognitive Impairment in Midlife: Evidence from the 1958 British Birth Cohort
Authors: Sahota Chanthie Menika , Cable Noriko , Cadar Dorina
Published: January 2024

Background

Dementia has been the leading cause of death in the UK since 2015. Increasing evidence supports an association between socioeconomic position (SEP) and dementia onset in later life. However, limited studies have examined how life-course SEP influences the development of mild cognitive impairment (MCI), an intermediate state potentially preceding dementia. Therefore, the present study aims to examine the relationship between life-course SEP and MCI amongst adults aged 50 years in Great Britain.

Methods

We employed data from the National Child Development Study (NCDS), also known as the 1958 British Birth Cohort, to determine the associations between SEP and MCI in 6590 participants. We categorised life-course measures of SEP as stable high/low or moving upward/downward over the life course. We assessed MCI at age 50 using one standard deviation below the averaged combined scores from all cognitive tests available. We then used binary logistic regression to estimate the longitudinal associations between life-course SEP and MCI.

Results

Relative to those of a high SEP across the life course, participants who moved upward, downward, or remained at a low SEP were significantly associated with 25% (95% CI 1.02–1.54, p = 0.035), 70% (95% CI 1.27–2.27, p < 0.001), and 85% (95% CI 1.50–2.29, p < 0.001), respectively, higher odds of MCI, independent of all selected covariates.

Conclusions

Lower life-course SEP was associated with significantly higher odds of MCI onset in middle life within the NCDS cohort. Public health policies targeting cognitive impairment should encompass a life-course approach to reduce socioeconomic inequalities.
Association of Paternal Age Alone and Combined with Maternal Age with Perinatal Outcomes: A Prospective Multicenter Cohort Study in China
Authors: Yin Shaohua , Zhou Yubo , Zhao Cheng , Yang Jing , Yuan Pengbo , Zhao Yangyu , Qi Hongbo , Wei Yuan
Published: January 2024

Maternal and paternal age at birth is increasing globally. Maternal age may affect perinatal outcomes, but the effect of paternal age and its joint effect with maternal age are not well established. This prospective, multicenter, cohort analysis used data from the University Hospital Advanced Age Pregnant Cohort Study in China from 2016 to 2021, to investigate the separate association of paternal age and joint association of paternal and maternal age with adverse perinatal outcomes. Of 16,114 singleton deliveries, mean paternal and maternal age (± SD) was 38.0 ± 5.3 years and 36.0 ± 4.1 years. In unadjusted analyses, older paternal age was associated with increased risks of gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy, preeclampsia, placenta accreta spectrum disorders, placenta previa, cesarean delivery (CD), and postpartum hemorrhage, preterm birth (PTB), large-for-gestational-age, macrosomia, and congenital anomaly, except for small-for-gestational-age. In multivariable analyses, the associations turned to null for most outcomes, and attenuated but still significant for GDM, CD, PTB, and macrosomia. As compare to paternal age of < 30 years, the risks in older paternal age groups increased by 31–45% for GDM, 17–33% for CD, 32–36% for PTB, and 28–31% for macrosomia. The predicted probabilities of GDM, placenta previa, and CD increased rapidly with paternal age up to thresholds of 36.4–40.3 years, and then plateaued or decelerated. The risks of GDM, CD, and PTB were much greater for pregnancies with younger paternal and older maternal age, despite no statistical interaction between the associations related to paternal and maternal age. Our findings support the advocation that paternal age, besides maternal age, should be considered during preconception counseling.

Trial Registration NCT03220750, Registered July 18, 2017—Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT03220750.
Cutaneous Leishmaniasis Hampers COVID-19: A Controlled Cross-Sectional Study in High-Burden Endemic Areas of Iran
Authors: Bamorovat Mehdi , Sharifi Iraj , Shafiei Bafti Mehdi , Agha Kuchak Afshari Setareh , Aflatoonian Mohammad Reza , Karamoozian Ali , Jafarzadeh Abdollah , Amirzadeh Raheleh , Khosravi Ahmad , Babaei Zahra , Safa Farzane , Sharifi Fatemeh , Heshmatkhah Amireh
Published: January 2024

Introduction

Emerging infectious diseases such as SARS-CoV-2 can cause pandemics and create a critical risk for humans. In a previous pilot study, we reported that the immunological responses induced by cutaneous leishmaniasis (CL) could decrease the incidence and severity of COVID-19. In this large-scale case–control study, we assessed the possible relationship between mortality and morbidity of COVID-19 in healed CL persons suffering scars compared to cases without CL history.

Methods

This controlled cross-sectional study was conducted between July 2020 and December 2022 in the endemic and high-burden areas of CL in southeastern Iran. In the study, 1400 previous CL cases with scars and 1,521,329 subjects who had no previous CL were analyzed. We used R 4.0.2 to analyze the data. Firth’s bias reduction approach corresponding to the penalization of likelihood logistic regression by Jeffreys was also employed to influence the variables in the dataset. Also, a Bayesian ordinal logistic regression model was performed to explore the COVID-19 severity in both case and referent groups.

Results

The occurrence and severity rate of COVID-19 in CL scar cases are significantly less than in the non-CL control group, while in the CL scar subjects, patients with critical conditions and mortality were not observed. The morbidity (OR = 0.11, CI 0.06–0.20 and P < 0.001) and severity of COVID-19 in previous cases with CL scars were significantly diminished than that in the control group (credible interval − 2.57, − 1.62).

Conclusions

The results represented a durable negative relationship between cured CL and COVID-19 incidence and severity. Additional studies seem necessary and should be designed to further validate the true impact and underlying mechanistic action of CL on COVID-19.

Graphical abstract
Wind tunnel and numerical study of outdoor particle dispersion around a low-rise building model
Authors: Zhao Runmin , Liu Junjie , Jiang Nan , Liu Sumei
Published: January 2024

The dispersion of particulate pollutants around buildings raises concerns due to adverse health impacts. Accurate prediction of particle dispersion is important for evaluating health risks in urban areas. However, rigorous validation data using particulate tracers is lacking for numerical models of urban dispersion. Many prior studies rely on gas dispersion data, questioning conclusions due to differences in transport physics. To address this gap, this study utilized a combined experimental and computational approach to generate comprehensive validation data on particulate dispersion. A wind tunnel experiment using particulate tracers measured airflow, turbulence, and particle concentrations around a single building, providing reliable but sparse data. Validated large eddy simulation expanded the data. This combined approach generated much-needed validation data to evaluate numerical particle dispersion models around buildings. Steady Reynolds-averaged Navier–Stokes (SRANS) simulations paired with Lagrangian particle tracking (LPT), and drift-flux (DF) models were validated. SRANS had lower accuracy compared to LES for airflow and turbulence. However, in this case, SRANS inaccuracies did not prevent accurate concentration prediction when LPT or a Stokes drift-flux model were used. The algebraic drift-flux model strongly overpredicted the concentration for large micron particles, indicating proper drift modeling was essential.
Contemporary Australian Tort Law
Authors: Kyriakakis Joanna , Popa Tina , Rochford Francine , Szablewska Natalia , Zhao Xiaobo , Taliadoros Jason , O'Donovan Darren , Bautista Lowell
Published: January 2024

Tort law is a dynamic area of Australian law, offering individuals the opportunity to seek legal remedies when their interests are infringed. Contemporary Australian Tort Law introduces the fundamentals of tort law in Australia today in an accessible, student-friendly way. This edition retains the logical coverage of key aspects of tort law and has been thoroughly updated to cover recent case law and legal developments. The chapter on defamation has been comprehensively updated to reflect recent amendments to uniform legislation and its application in common law. Self-assessment tools throughout the text encourage students to test and apply their knowledge of key concepts. These features include case questions and review questions throughout each chapter, as well as longer end-of-chapter hypothetical problems which consolidate students' application of key concepts to realistic contemporary scenarios. Written by a team of teaching experts, Contemporary Australian Tort Law is an engaging resource for students new to studying tort law.
The Mediation of Autocratic Regimes: How Local Officials Shaped Authoritarian Systems in Rwanda and Sudan
Authors: Desrosiers Marie-Eve , Mahé Anne-Laure
Published: January 2024

Local state officials impact authoritarian systems through the mediation they perform. Desrosiers and Mahé argue that these local functionaries fulfill a number of mediating functions, including translating and representing authoritarian systems at the local level. By enacting these two roles, however, local officials do not straightforwardly reproduce the system. Instead, their interpretations and choices fundamentally influence the imprint authoritarianism has on society, from how the regime is experienced at the local level to its groundings and resilience. They demonstrate this argument by looking at pre-genocide Rwanda and Sudan under President Omar al-Bashir.
Impact of Non-Motor Symptoms on Quality of Life in Patients with Early-Onset Parkinson’s Disease
Authors: Patwardhan Ameya , Kamble Nitish , Bhattacharya Amitabh , Holla Vikram , Yadav Ravi , Pal Pramod Kumar
Published: January 2024

Background:

Early-onset Parkinson’s disease (EOPD) refers to patients with Parkinson’s disease (PD) whose age at disease onset is less than 50 years. Literature on the non-motor symptoms (NMS) in these patients is very limited in the Indian context. We aimed to study the NMS in patients with EOPD and its impact on the quality of life (QoL).

Methods:

We included 124 patients with EOPD with a mean age at disease onset between 21 and 45 years and 60 healthy controls (HC). NMS were assessed using validated scales, and the QoL domains were evaluated using the PD QoL–39 scale (PDQ-39).

Results:

The mean age at disease onset in EOPD patients was 37.33 ± 6.36 years. Majority of the patients were male (66.12%). The average disease duration was 6.62 ± 5.3 years. EOPD patients exhibited a significantly higher number of NMS per patient (7.97 ± 4.69) compared to HC (1.3 ± 1.39; p < 0.001). The most common NMS reported were urinary dysfunction, body pain, poor sleep quality, constipation, anxiety, depression, cognitive impairment, and REM sleep behavior disorder. The total NMS burden correlated with the QoL measures. Distinctive patterns of QoL subdomain involvement were identified, with sleep/fatigue, mood/cognition, and urinary dysfunction independently influencing QoL metrics.

Conclusions:

Our study provides valuable insights into the NMS profile and its impact on QoL in patients with EOPD, addressing an important knowledge gap in the Indian context. By understanding the specific NMS and their influence on QoL, healthcare professionals can develop targeted interventions to address these symptoms and improve the overall QoL.
The stable cohomology of self-equivalences of connected sums of products of spheres
Authors: Stoll Robin
Published: January 2024

We identify the cohomology of the stable classifying space of homotopy automorphisms (relative to an embedded disk) of connected sums of

${\mathrm {S}^{k}} \times {\mathrm {S}^{l}}$

, where

$3 \le k < l \le 2k - 2$

. The result is expressed in terms of Lie graph complex homology.
Complexity as Epistemic Oppression: Writing People with Intellectual Disabilities Back into Philosophical Conversations
Authors: Monteleone Rebecca
Published: January 2024

Formal Language

In this essay, I reflect on the systematic exclusion of people with intellectual disabilities from philosophy even as their personhood is subject to ongoing philosophical debates. Theorizing this disenfranchisement as a form of epistemic oppression, I consider it in the context of the invalidation of disabled perspectives more broadly and characteristics of knowledge-production that confer credibility in philosophy. I end with a call for transformation through the framework of disability justice. I include an Easy Read summary, a plain language companion, and discussion questions, which restate my argument in simplified language and invite dialogue, demonstrating how philosophy might resist epistemic gatekeeping and imagine knowledge-production otherwise.

Plain Language

This essay is about philosophy and intellectual disability (ID). People with ID do not get to do philosophy very much. Some reasons they are left out are:

–

Disabled people are not believed when they talk about their lives.

–

The way we write in philosophy makes it hard for people with ID to join.

I think we should change how we do philosophy. I wrote a summary that is easy to read. I wrote questions to talk about together. I want to think about how to do philosophy better.

Easy Read Summary

Philosophers are thinkers.They think about how the world is and how it should be.They think about intellectual disability (ID).Some thinkers say people with intellectual disabilities (ID) are worth less than other people.Most people with intellectual disabilities (ID) do not get to say what they think.We can change how we think by including people with intellectual disabilities (ID).We can believe what people with intellectual disabilities (ID) say about their lives.We can write and speak in simple ways.We can give people help thinking and making decisions.We can include people who do not speak or write.We can think as a community.