bluuebunny/crossref_metadata_2025 huggingface dataset:
30 years of life of the Heureka project
Authors: Dvořák L , Dvořáková I , Koudelková V , Gottwald S
Published: March 2024

Heureka (“Eureka” in English) is a long-term project aimed at improving physics education in lower and upper secondary schools in the Czech Republic. It began informally “from below” about 30 years ago. Since then, it has expanded to include three series of weekend seminars for physics teachers, along with various other activities such as the annual conference. The project’s proceedings are freely available on the Heureka website for teachers; many other materials can be found on the wiki for participants. Despite the restrictions due to covid pandemic, the project has continued to thrive, maintaining its inquiry-based teaching approach and active learning style even in the online environment. This paper provides more detailed information about the project, feedback from participants, and the lessons learned from the experience. We hope that this information will prove useful and inspiring for leaders of similar projects targeting physics teachers.
Developing the experimental skills of pre-service physics teachers
Authors: Juhásová Antónia , Kireš Marián
Published: March 2024

In this paper we present the focus, objectives, content and implementation of the elective course Selected Demonstration Experiments designed for physics teaching students. We map students’ personal experiences with the implementation of physics experiments in lower secondary school and high school, as well as their knowledge of the possibilities of demonstrating physical phenomena through experiments with simple tools. The continuing lack of experimentally oriented activities in physics education naturally has a negative impact on the experimental skills of physics teaching students. In this context, the prospective teacher should be able to carry out a wide range of physical experiments, demonstrations, experiments and measurements, interpret them appropriately and involve them in active perception. The lack of experimental equipment in schools for individual (or small group) student work can be at least partially overcome by the use of commonly available simple tools (plastic containers, stationery household tools, toys). Their availability is a strong motivation for individual observations, investigations and measurements at home. In the school laboratory, the teacher can easily provide such tools for frontal experiments, parallel work by groups of students or project work following observations at home. We consider and present a model of blended learning in an educational laboratory environment. In this paper we present selected ideas for physics observations and experiments with simple tools in the form of engaging video demonstrations. We have included the creation of our own educational video demonstration as a student semester project in the course presented. We present the success of achieving our learning objectives through student assessment.
Eyetracking identification of cognitive decision-making modes in STEM education - a case study
Authors: Rosiek R , Sajka M
Published: March 2024

We present a description and oculographic characterisation of task solving methods on the basis of eyetracking research carried out on a group of 60 university students, of various specialisations, within the age bracket of 20-21. We also provide preliminary answers to two questions: Does eyetracking identify cognitive decision-making modes? If so, which oculographic parameters are the most useful for this purpose? In this paper, we present a selected fragment of the results obtained from a series of tasks with a difficulty level not exceeding that of secondary school, based on a task concerning the interpretation of changes in the distance from the ground at a selected point of a carousel during its movement. In addition, the study concerns university students’ difficulties in interpreting graphs.
Path planning of complicated hierarchical thin-wall structures using multi-material additive manufacturing technology
Authors: Niu Chengcheng , Luan Congcong , Shen Hongyao , Fu Jianzhong
Published: March 2024

Multilayer thin-wall structures have demonstrated significant application potential in wearable devices, pressure vessels, and aerospace industries, with additive manufacturing (AM) poised to further unlock their capabilities. Although path planning, a crucial aspect of AM, has been extensively studied for homogeneous structures, research on path planning for heterogeneous structures remains limited. This study introduces a novel path planning algorithm, termed CPCNHTS, for generating continuous paths in complex non-rotating bodies with hierarchical thin-walled structures. CPCNHTS encompasses adaptive slicing, path offset, and robotic postprocessing techniques. The adaptive slicing method is employed to enhance the slicing model’s accuracy through volume error control. Moreover, the path offset method is designed to derive the printing path using a parallel curve of the inner contour. Identification of the inner contour is based on the curvatures and areas of single and double contours, respectively. The robotic postprocessing method is employed to convert the printing path into executable codes for multimaterial additive equipment. As a compelling application of the CPCNHTS algorithm, a limb prosthetic socket was successfully fabricated, highlighting the remarkable potential of this approach within the wearable devices domain.
Regularity of sections of CR vector bundles
Authors: Lamel Bernhard , Mir Nordine
Published: March 2024

In this note, we show that every generalized section

σ
\sigma

of a CR vector bundle

E
E

over a CR manifold

M
M

has the property that near most points of its singular support, there exists a proper abstract CR subbundle

F
⊂
E

F \subset E

which has the property that every real subbundle of

E
E

which contains the image of

σ
\sigma

also contains

F
F

.
Enhanced polygenic risk score incorporating gene–environment interaction suggests the association of major depressive disorder with cardiac and lung function
Authors: Pan Chuyu , Cheng Bolun , Qin Xiaoyue , Cheng Shiqiang , Liu Li , Yang Xuena , Meng Peilin , Zhang Na , He Dan , Cai Qingqing , Wei Wenming , Hui Jingni , Wen Yan , Jia Yumeng , Liu Huan , Zhang Feng
Published: March 2024

Background

Depression has been linked to an increased risk of cardiovascular and respiratory diseases; however, its impact on cardiac and lung function remains unclear, especially when accounting for potential gene–environment interactions.

Methods

We developed a novel polygenic and gene–environment interaction risk score (PGIRS) integrating the major genetic effect and gene–environment interaction effect of depression-associated loci. The single nucleotide polymorphisms (SNPs) demonstrating major genetic effect or environmental interaction effect were obtained from genome-wide SNP association and SNP-environment interaction analyses of depression. We then calculated the depression PGIRS for non-depressed individuals, using smoking and alcohol consumption as environmental factors. Using linear regression analysis, we assessed the associations of PGIRS and conventional polygenic risk score (PRS) with lung function (N = 42 886) and cardiac function (N = 1791) in the subjects with or without exposing to smoking and alcohol drinking.

Results

We detected significant associations of depression PGIRS with cardiac and lung function, contrary to conventional depression PRS. Among smokers, forced vital capacity exhibited a negative association with PGIRS (β = −0.037, FDR = 1.00 × 10−8), contrasting with no significant association with PRS (β = −0.002, FDR = 0.943). In drinkers, we observed a positive association between cardiac index with PGIRS (β = 0.088, FDR = 0.010), whereas no such association was found with PRS (β = 0.040, FDR = 0.265). Notably, in individuals who both smoked and drank, forced expiratory volume in 1-second demonstrated a negative association with PGIRS (β = −0.042, FDR = 6.30 × 10−9), but not with PRS (β = −0.003, FDR = 0.857).

Conclusions

Our findings underscore the profound impact of depression on cardiac and lung function, highlighting the enhanced efficacy of considering gene–environment interactions in PRS-based studies.
Magnetic resonance imaging of placental intralobule structure and function in a preclinical nonhuman primate model
Authors: Melbourne Andrew , Schabel Matthias C , David Anna L , Roberts Victoria H J
Published: March 2024

Although the central role of adequate blood flow and oxygen delivery is known, the lack of optimized imaging modalities to study placental structure has impeded our understanding of its vascular function. Magnetic resonance imaging is increasingly being applied in this field, but gaps in knowledge remain, and further methodological developments are needed. In particular, the ability to distinguish maternal from fetal placental perfusion and the understanding of how individual placental lobules are functioning are lacking. The potential clinical benefits of developing noninvasive tools for the in vivo assessment of blood flow and oxygenation, two key determinants of placental function, are tremendous. Here, we summarize a number of structural and functional magnetic resonance imaging techniques that have been developed and applied in animal models and studies of human pregnancy over the past decade. We discuss the potential applications and limitations of these approaches. Their combination provides a novel source of contrast to allow analysis of placental structure and function at the level of the lobule. We outline the physiological mechanisms of placental T2 and T2* decay and devise a model of how tissue composition affects the observed relaxation properties. We apply this modeling to longitudinal magnetic resonance imaging data obtained from a preclinical pregnant nonhuman primate model to provide initial proof-of-concept data for this methodology, which quantifies oxygen transfer and placental structure across and between lobules. This method has the potential to improve our understanding and clinical management of placental insufficiency once validation in a larger nonhuman primate cohort is complete.
Site-selective arene C–H functionalization by cooperative metal catalysis
Authors: Nakao Yoshiaki
Published: March 2024

Efforts made over the past 3 decades have led to the development of various organic transformations that directly convert unfunctionalized C–H bonds into functional groups by metal catalysis. However, many of these transformations are restricted to specific reaction sites controlled by directing groups, which bring the metal centers into proximity with the C–H bonds being functionalized. These directing groups are typically tailored for specific C–H functionalization reactions, necessitating additional steps for their installation and removal, thereby limiting overall utility and efficiency. There is a strong desire to achieve site-selectivity control using catalysts with compounds bearing common functional groups. We have investigated catalytic Lewis-pair formations to electronically activate substrates and control the site selectivity of metal-catalyzed arene C–H functionalization. In this account, we present C–C and C–B bond-forming reactions through cooperative transition metal/Lewis acid (LA) catalysis. Common LA catalysts derived from Zn, B, and Al have been demonstrated as highly efficient co-catalysts for Ni- and Ir-catalyzed arene C–H functionalization. Steric repulsion between the LA and Ni or Ir catalysts facilitates para-selective C–H functionalization, while ligands bearing LA moieties effectively control meta-selectivity.
Incremental cost analysis model of distribution network based on economic dispatch of distributed new-energy storage system
Authors: Zhou Zhuan , Bian Jiayu , Yu Zhiyong
Published: March 2024

With the implementation of China’s carbon-peaking and carbon-neutrality strategy, new energy will achieve leapfrog growth. Due to the good economics of distributed new-energy generation, it can not only save users’ own investment, but also help to achieve local consumption of new energy. However, it will also bring about a series of incremental costs to the power grid. This paper first enumerates the concept, development status and scheduling mode of a distributed new-energy storage system. Based on the above, it establishes a new-energy power generation model and an energy storage system charging and discharging model, and proposes a global optimization scheduling model for a distributed new-energy storage system, considering the time-of-use electricity price and taking the lowest total operating cost of the distributed new-energy power generation system as the objective function. Finally, it proposes a distribution network incremental cost analysis model based on the penetration of distributed new energy. The calculation results show that the incremental cost of grid-connected distributed new energy is 1.0849, 1.2585 and 1.3473 yuan/kWh, respectively, which indicates that the global dispatching model can optimize the power consumption structure of a distributed power generation system, and has the function of peak shaving and valley filling, but the incremental cost of the distribution network will also increase.
Plasma homocysteine level, estradiol level, and brain atrophy: a Mendelian randomization study
Authors: Gao Wen , Zhu Wei-Wen , Yu Ya-Huan , Wang Juan
Published: March 2024

Objectives

Observational studies link elevated plasma homocysteine (Hcy) with vascular disease. Our aim was to assess the gender difference in the association between the plasma tHcy level and brain atrophy and identify the possible influencer. We employed Mendelian randomization (MR) to explore the causal relationship between plasma tHcy level, estradiol level, and brain atrophy.

Methods

A total of 687 patients with brain atrophy were included, and gender-specific subgroup analyses in association between tHcy and brain atrophy are conducted. From genome-wide association studies, we selected genetic variants (P < 5 × 10−8) for the plasma tHcy level and estradiol level. We investigated the degree of brain atrophy (including gray matter volume and total brain volume) in the UK biobank (n = 7,916). The inverse variance–weighted and several sensitivity MR regression analyses were carried out.

Results

The plasma tHcy level was significantly associated with brain atrophy for females, but not for males. An MR study showed that there was little evidence of the causal link between elevated plasma tHcy and brain atrophy. On the other hand, we found evidence to support causality for genetically decreased estradiol with higher risk of brain atrophy. Furthermore, genetic predisposition to elevated plasma tHcy was associated with a lower estradiol level.

Conclusions

The influence of estradiol on the association between tHcy and brain atrophy deserves further investigation.
Nuclear Medicine Imaging Tools in Fever of Unknown Origin: Time for a Revisit and Appropriate Use Criteria
Authors: Wright William F , Kandiah Sheetal , Brady Rebecca , Shulkin Barry L , Palestro Christopher J , Jain Sanjay K
Published: March 2024

Fever of unknown origin (FUO) is a clinical conundrum for patients and clinicians alike, and imaging studies are often performed as part of the diagnostic workup of these patients. Recently, the Society of Nuclear Medicine and Molecular Imaging convened and approved a guideline on the use of nuclear medicine tools for FUO. The guidelines support the use of 2-18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in adults and children with FUO. 18F-FDG PET/CT allows detection and localization of foci of hypermetabolic lesions with high sensitivity because of the 18F-FDG uptake in glycolytically active cells that may represent inflammation, infection, or neoplasia. Clinicians should consider and insurers should cover 18F-FDG PET/CT when evaluating patients with FUO, particularly when other clinical clues and preliminary studies are unrevealing.
Evaluating the effect of inequalities in oral anti-coagulant prescribing on outcomes in people with atrial fibrillation
Authors: Mulholland Ryan J , Manca Francesco , Ciminata Giorgio , Quinn Terry J , Trotter Robert , Pollock Kevin G , Lister Steven , Geue Claudia
Published: March 2024

Aims

Whilst anti-coagulation is typically recommended for thromboprophylaxis in atrial fibrillation (AF), it is often never prescribed or prematurely discontinued. The aim of this study was to evaluate the effect of inequalities in anti-coagulant prescribing by assessing stroke/systemic embolism (SSE) and bleeding risk in people with AF who continue anti-coagulation compared with those who stop transiently, permanently, or never start.

Methods and results

This retrospective cohort study utilized linked Scottish healthcare data to identify adults diagnosed with AF between January 2010 and April 2016, with a CHA2DS2-VASC score of ≥2. They were sub-categorized based on anti-coagulant exposure: never started, continuous, discontinuous, and cessation. Inverse probability of treatment weighting-adjusted Cox regression and competing risk regression was utilized to compare SSE and bleeding risks between cohorts during 5-year follow-up. Of an overall cohort of 47 427 people, 26 277 (55.41%) were never anti-coagulated, 7934 (16.72%) received continuous anti-coagulation, 9107 (19.2%) temporarily discontinued, and 4109 (8.66%) permanently discontinued. Lower socio-economic status, elevated frailty score, and age ≥ 75 were associated with a reduced likelihood of initiation and continuation of anti-coagulation. Stroke/systemic embolism risk was significantly greater in those with discontinuous anti-coagulation, compared with continuous [subhazard ratio (SHR): 2.65; 2.39–2.94]. In the context of a major bleeding event, there was no significant difference in bleeding risk between the cessation and continuous cohorts (SHR 0.94; 0.42–2.14).

Conclusion

Our data suggest significant inequalities in anti-coagulation prescribing, with substantial opportunity to improve initiation and continuation. Decision-making should be patient-centred and must recognize that discontinuation or cessation is associated with considerable thromboembolic risk not offset by mitigated bleeding risk.
The interkingdom horizontal gene transfer in 44 early diverging fungi boosted their metabolic, adaptive, and immune capabilities
Authors: Ciach Michał Aleksander , Pawłowska Julia , Górecki Paweł , Muszewska Anna
Published: March 2024

Numerous studies have been devoted to individual cases of horizontally acquired genes in fungi. It has been shown that such genes expand the hosts’ metabolic capabilities and contribute to their adaptations as parasites or symbionts. Some studies have provided an extensive characterization of the horizontal gene transfer (HGT) in Dikarya. However, in the early diverging fungi (EDF), a similar characterization is still missing. In order to fill this gap, we have designed a computational pipeline to obtain a statistical sample of reliable HGT events with a low false discovery rate. We have analyzed 44 EDF proteomes and identified 829 xenologs in fungi ranging from Chytridiomycota to Mucoromycota. We have identified several patterns and statistical properties of EDF HGT. We show that HGT is driven by bursts of gene exchange and duplication, resulting in highly divergent numbers and molecular properties of xenologs between fungal lineages. Ancestrally aquatic fungi are generally more likely to acquire foreign genetic material than terrestrial ones. Endosymbiotic bacteria can be a source of useful xenologs, as exemplified by NOD-like receptors transferred to Mortierellomycota. Closely related fungi have similar rates of intronization of xenologs. Posttransfer gene fusions and losses of protein domains are common and may influence the encoded proteins’ functions. We argue that there is no universal approach for HGT identification and inter- and intra-kingdom transfers require tailored identification methods. Our results help to better understand how and to what extent HGT has shaped the metabolic, adaptive, and immune capabilities of fungi.
Glycosylation as a tracer of off-target Cre-lox activation in development
Authors: Glendenning Leandre M , Reynero Kalob M , Cobb Brian A
Published: March 2024

The Cre-lox system is one of the most widely used methods for lineage-specific and inducible genome editing in vivo. However, incomplete penetrance and off-target effects due to transient promoter expression in a stem or pluripotent precursor cell can be problematic and difficult to detect, especially if the target gene is not normally present in the fully differentiated but off-target cells. Yet, the loss of the target gene through the transient expression of Cre may impact the differentiation of those cells by virtue of transient expression in a precursor population. In these situations, off-target effects in an unknown precursor cell can, at best, complicate conclusions drawn from the model, and at worst, invalidate all data generated from that knockout strain. Thus, identifying Cre-driver promoter expression along entire cell lineages is crucial to improve rigor and reproducibility. As an example, transient expression in an early precursor cell has been documented in a variety of Cre strains such as the Tie2-based Cre-driver system that is used as an “endothelial cell-specific” model 1. Yet, Tie2 is now known to be transiently expressed in a stem cell upstream of both hematopoietic and endothelial cell lineages. Here, we use the Tie2 Cre-driver strain to demonstrate that due to its ubiquitous nature, plasma membrane glycans are a useful marker of both penetrance and specificity of a Cre-based knockout.
Bacterial diversity and chemical ecology of natural product–producing bacteria from Great Salt Lake sediment
Authors: Bring Horvath Elijah R , Brazelton William J , Kim Min Cheol , Cullum Reiko , Mulvey Matthew A , Fenical William , Winter Jaclyn M
Published: March 2024

Great Salt Lake (GSL), located northwest of Salt Lake City, UT, is the largest terminal lake in the USA. While the average salinity of seawater is ~3.3%, the salinity in GSL ranges between 5% and 28%. In addition to being a hypersaline environment, GSL also contains toxic concentrations of heavy metals, such as arsenic, mercury, and lead. The extreme environment of GSL makes it an intriguing subject of study, both for its unique microbiome and its potential to harbor novel natural product–producing bacteria, which could be used as resources for the discovery of biologically active compounds. Though work has been done to survey and catalog bacteria found in GSL, the Lake’s microbiome is largely unexplored, and little to no work has been done to characterize the natural product potential of GSL microbes. Here, we investigate the bacterial diversity of two important regions within GSL, describe the first genomic characterization of Actinomycetota isolated from GSL sediment, including the identification of two new Actinomycetota species, and provide the first survey of the natural product potential of GSL bacteria.
Genomics to detect transmission of livestock-associated methicillin-resistant Staphylococcus aureus from UK pigs in abattoirs during slaughter
Authors: Anjum Muna F , Duggett Nicholas , Sheldon Ewart , Sharma Meenaxi , Smith Richard P , Teale Chris J
Published: March 2024

Background

Livestock-associated MRSA (LA-MRSA) transmission/cross-contamination can occur at abattoir through colonized pigs, increasing occupational hazards and health concerns for workers. To assess this risk we used genomics to identify LA-MRSA lineages present in batches of pigs sent to slaughter and distribution of clones.

Methods

WGS was performed on 85 LA-MRSA previously isolated from six abattoirs from 105 batches of pigs sent from 100 UK farms. spa typing and MLST were performed on all isolates. A mashtree tree was constructed to compare genomes of the LA-MRSA with 1281 global isolates from livestock and humans. A phylogenetic tree and pairwise SNP distance matrices were built from whole genomes of 109 isolates closest to those from abattoirs to compare evolutionary relationships and identify clones.

Results

All abattoir isolates belonged to CC398 and were mainly of spa type t011, although other spa types were present. Phylogenetic analysis confirmed the abattoir isolates were most closely related to each other and to pig LA-MRSA from across Europe, indicating a common evolutionary origin with related lineages colonizing UK pigs.

Comparison of genomes using SNPs suggested between one and four clones were transferring between pigs from different batches. Transmission likely occurred on farm premises, during transportation, and/or within abattoirs through contact with contaminated surfaces in lairage or post-stunning.

Conclusions

Genomics forensically identified related isolates/clones circulating in pigs at slaughter, showing contamination occurs often. Results suggest that further genomic tracking will identify hotspots, and improvements in measures such as biosecurity and disinfection will help reduce risk for workers.
14-Year Epidemiologic study of Pseudomonas aeruginosa bloodstream infection incidence and resistance in the Veterans Health Administration system, 2009–2022
Authors: Hojat Leila S , Wilson Brigid M , Satlin Michael J , Perez Federico , Mojica Maria F , Singer Mendel E , Bonomo Robert A , Epstein Lauren H
Published: March 2024

Background

Multidrug resistant Pseudomonas aeruginosa (PA) represents a serious threat to hospitalized patients. Characterizing the incidence of PA infection and degree of resistance can inform empiric treatment and preventative measures.

Objectives

We sought to describe trends in incidence and resistance characteristics of PA bloodstream infections (BSI) observed within the Veterans Health Administration (VHA) system and identify factors contributing to higher observed mortality within this population.

Methods

We characterized demographic and clinical features of unique patients among the VHA population presenting with their first episode of PA-BSI between 2009 and 2022 and summarized trends related to mortality and resistance phenotype based on year and geographical location. We additionally used logistic regression analysis to identify predictors of 30-day mortality among this cohort.

Results

We identified 8039 PA-BSIs during the study period, 32.7% of which were hospital onset. Annual PA-BSI cases decreased by 35.8%, and resistance among all antimicrobial classes decreased during the study period, while the proportion of patients receiving early active treatment based on susceptibility testing results increased. Average 30-day mortality rate was 23.3%. Higher Charlson Comorbidity Index, higher mAPACHE score, VHA facility complexity 1b and hospital-onset cases were associated with higher mortality, and early active treatment was associated with lower mortality.

Conclusions

PA-BSI resistance decreased across the VHA system during the study period. Further investigation of antimicrobial stewardship measures possibly contributing to the observed decreased resistance in this cohort and identification of measures to improve on the high mortality associated with PA-BSI in the VHA population is warranted.
Identification of an novel genetic variant associated with osteoporosis: insights from the Taiwan Biobank Study
Authors: Liaw Yi-Ching , Matsuda Koichi , Liaw Yung-Po
Published: March 2024

Purpose

The purpose of this study was to identify new independent significant SNPs associated with osteoporosis using data from the Taiwan Biobank (TWBB).

Material and Methods

The dataset was divided into discovery (60%) and replication (40%) subsets. Following data quality control, genome-wide association study (GWAS) analysis was performed, adjusting for sex, age, and the top 5 principal components, employing the Scalable and Accurate Implementation of the Generalized mixed model approach. This was followed by a meta-analysis of TWBB1 and TWBB2. The Functional Mapping and Annotation (FUMA) platform was used to identify osteoporosis-associated loci. Manhattan and quantile–quantile plots were generated using the FUMA platform to visualize the results. Independent significant SNPs were selected based on genome-wide significance (P < 5 × 10−8) and independence from each other (r2 < 0.6) within a 1 Mb window. Positional, eQTL(expression quantitative trait locus), and Chromatin interaction mapping were used to map SNPs to genes.

Results

A total of 29 084 individuals (3154 osteoporosis cases and 25 930 controls) were used for GWAS analysis (TWBB1 data), and 18 918 individuals (1917 cases and 17 001 controls) were utilized for replication studies (TWBB2 data). We identified a new independent significant SNP for osteoporosis in TWBB1, with the lead SNP rs76140829 (minor allele frequency = 0.055, P-value = 1.15 × 10−08). Replication of the association was performed in TWBB2, yielding a P-value of 6.56 × 10−3. The meta-analysis of TWBB1 and TWBB2 data demonstrated a highly significant association for SNP rs76140829 (P-value = 7.52 × 10−10). In the positional mapping of rs76140829, 6 genes (HABP2, RP11-481H12.1, RNU7-165P, RP11-139 K1.2, RP11-57H14.3, and RP11-214 N15.5) were identified through chromatin interaction mapping in mesenchymal stem cells.

Conclusions

Our GWAS analysis using the Taiwan Biobank dataset unveils rs76140829 in the VTI1A gene as a key risk variant associated with osteoporosis. This finding expands our understanding of the genetic basis of osteoporosis and highlights the potential regulatory role of this SNP in mesenchymal stem cells.
Mouse mandibular–derived osteoclast progenitors have differences in intrinsic properties compared with femoral–derived progenitors
Authors: Clark Rachel , Park Soo Y , Bradley Elizabeth W , Mansky Kim , Tasca Amy
Published: March 2024

Craniofacial osteoclasts are essential for site–specific processes such as alveolar bone resorption, tooth eruption, and orthodontic tooth movement. Much of the current understanding of osteoclast development and function comes from studies using long bone–derived cells. Minimal investigation has been done to explore skeletal site differences. The overall goal of this study was to determine if mandibular– and femoral–derived osteoclasts represent distinct populations. To test this hypothesis, bone marrow cells were initially analyzed from the mandible and femur of 2–month–old mice. It was shown that mandibular–derived osteoclasts have enhanced size (mm2) compared with femoral–derived osteoclasts. Since bone marrow macrophages are a heterogenous population, we additionally selected for monocytes and demonstrated that mandibular–derived monocytes also form osteoclasts with increased size compared with femoral–derived monocytes. Osteoclast precursor populations from both skeletal sites were analyzed by flow cytometry. A newly described Ly6CHigh+ population as well as the Ly6Cint population was increased in the mandibular–derived cells. The difference in differentiation potential between monocyte cultures suggests that the increase in the Ly6CHigh+ population may explain the enhanced differentiation potential in mandibular–derived cells. Monocyte genes such as Pu.1, C/ebp-a, and Prdm1 are increased in expression in mandibular–derived monocytes compared with femoral–derived monocytes. As expected with enhanced differentiation, osteoclast genes including Nfatc1, Dc-stamp, Ctsk, and Rank are upregulated in mandibular–derived osteoclast precursors. Future studies will determine how changes in the environment of the mandible lead to changes in percentages of osteoclast progenitors and their differentiation potential.
Round-up of English patent litigation 2023
Authors: Cook Trevor
Published: March 2024

2023 saw 15 decisions, concerning 22 patents, in inter partes proceedings in which patent infringement and/or validity was in issue. 6 patents were held to be valid and infringed, 9 not to be infringed and 9 to be invalid, all but 3 on the ground of obviousness. 2023 also saw 6 Court of Appeal decisions in such proceedings, in 3 of which the trial judge was reversed on validity - in two cases in favour of the patentee.
Publish and perish: mental health among communication and media scholars
Authors: Hanitzsch Thomas , Markiewitz Antonia , Bødker Henrik
Published: March 2024

Studies point to a significantly higher prevalence of mental health issues among academics compared to most other working populations. However, we know relatively little about the situation within the field of media and communication studies. Based on an international survey of 1028 researchers within this field, we found mental health issues to be widespread. Early career researchers, women, and those in nonpermanent positions were significantly more strongly affected by these issues than scholars in later career stages, men, and those in permanent employment. Academics in our field worry most about structural aspects of their work, most notably about publication pressure and future career prospects. We argue that while our findings are somewhat aligned with results from or across other fields, they are still worrisome. We thus argue for the need to start a conversation about how to reduce the mental burden, especially for young and early career researchers.
(008) Are Vibrators Equally Effective among Women Engaged in Partnered and Solo Sexually Activity?
Authors: Dubinskaya A , Jakson F , Kohli P , Shoureshi P , Eilber K
Published: March 2024

Introduction

Solo sexual activity is a solo stimulation of one’s genitals and other body areas for sexual pleasure. Treatment methods for Female Sexual Dysfunction (FSD), developed to date are usually assessed in the context of partnered sexual activity. There is a growing need to compare the effect of therapeutic interventions, like vibrators, among women engaged in only solo sexual activity and partnered sexual activity.

Objective

The aim of this study was to assess the effect of routine vibrator use on sexual health among women engaged in only solo and partnered sexual activity.

Methods

This was a prospectively pilot study of sexually active women aged 18 and 99 who presented for consultation to our urogynecological clinic with pelvic floor and/or sexual health concerns. Women were offered a bullet vibrator and instructed to use it according to the protocol. Participants’ demographics, health data, sexual practices, frequency of solo and partnered sexual activity, as well as Female Sexual Function Index (FSFI) were assessed at the initial visit and after three months of intervention. We used descriptive statistics and a paired-sample t-test to determine the effect of vibrator use on sexual function.

Results

Among 61 women enrolled in this study, 60.6% (n=37) were engaged in partnered sexual activity and 39.3% (n=24) were only solo sexually active. Participants were predominantly white (80.3%), with a mean age of 54.7 ± 16.3. There were no significant differences in demographics and pelvic floor disorders (prolapse, urinary incontinence) between the two groups. Vibrator use among women in a solo group did not show significant improvement in sexual response cycle domains (p>0.05). However, the score statistical trend was noted across all the domains. Women engaged in partnered sexual activity had significant improvement in desire (p=0.03), arousal (p=0.03), orgasm (p=0.05), and the total score (p=0.03) with vibrator use. The study completion was higher among women involved in partnered sexual activity 94.6% (n=35) than women who only engaged in solo sexual activity 58.3%(n=14).

Conclusions

No significant differences in demographics and pelvic health were noted between women engaged in solo sexual activity and women engaged in partnered sexual activity. Vibrator therapy produces significant improvement in desire, arousal, and orgasm domains, as well as total score among women in partnered sexual activities, also more represented in this pilot study.

Disclosure

No.
(020) Does Climate Impact IPP Infection Risk? Assessment of Temperature and Dew Point on IPP Infections
Authors: Hammad Muhammed Alaa Moukhtar , Barham David , Pyrgidis Nikolaos , Swerdloff Daniel , Miller Jake , Amini Eliad , Andrianne Robert , Burnett Arthur , Gross Kelli , Hatzichirstodoulou Georgios , Yafi Faysal A , Gross Martin
Published: March 2024

Introduction

Variations in climate have been associated with greater risk of surgical site infections, urinary tract infections, and changes in the skin microbiome. Although the pathogenic organisms for inflatable penile prosthesis (IPP) infections are commonly skin flora, limited data exists on the impact of climate on IPP infections. We sought to evaluate the impact of climate on the pathogenic organisms of IPP infections in a large international, multicenter cohort.

Objectives

To assess whether the time of the year, during which surgery was performed, affected device infections.

Methods

We performed a multi-institutional, retrospective study of patients undergoing IPP surgery. We then evaluated whether the month or season, during which surgery was performed, affected device infections. Additionally, we assessed the effect of temperature, dew point, and humidity on the microorganisms involved in implant infections. Infections were classified as Gram positive, Gram negative, or mixed (including a combination of Gram positive, Gram negative, and/or fungi). A univariate logistic regression analysis was undertaken.

Results

A total of 5289 patients with a mean age of 62.2 ± 10.8 years received IPP placement. A total of 103 (1.9%) infections were recorded. Overall, 38 (36.9%) infections were caused by Gram positive bacteria. An increase in temperature was associated with a higher risk of infection with Gram positive bacteria (OR: 1.03, 95% CI: 1 to 1.07, p = 0.035). No statistically significant differences were recorded in terms of season (p = 0.19) and month (p = 0.29).

Conclusion

Higher temperature is associated with greater risk of Gram positive infections whereas lower temperature and dew point were associated with a higher risk of mixed infections. These findings may help surgeons tailor antibiotic prophylaxis based on local climate.

Disclosure

No.
(266) Examining the Experience of Sexual Dysfunction and Spiritual Abuse among Cisgender Muslim Women in North America
Authors: Rahman S , Mohajir N , Ceesay H , Lamba A , Khayr Y , Bdaiwi M , Akhthar W , Spitz G
Published: March 2024

Introduction

Muslim women are an underrepresented and underserved population in North America who often do not seek care for their sexual traumas and sexual difficulties. In order to better serve this population with minimal bias, it is important for healthcare providers to understand their vast experiences with spiritual abuse and sexual dysfunction, as well as reasons for not seeking healthcare related to sexual dysfunction.

Objective

To understand the experiences of cisgender Muslim women in North America with regards to sexual function, sexual abuse and spiritual abuse.

Methods

To investigate these topics, a survey was administered to 771 Muslims between the ages of 18–45 who live in the US and Canada 2020. The majority of respondents were heterosexual females, were part of the Sunni sect of Islam, had a bachelor’s degree or higher, and were of South Asian, Asian, Middle Eastern, or Arab ancestry. Aspects of sexual functioning such as the frequency of sexual desire, arousal during sexual intercourse, achievement of orgasm, and pain during or after vaginal penetration were assessed.

Results

Of the 158 respondents who reported having experienced sexual pain, only 34.4% sought healthcare for this problem. The most commonly cited reasons included fear or shame, unawareness, doubt that the situation would improve, and resolution of the pain on its own. 530 participants were asked if religion or spirituality have been used to: force them to make decisions they are opposed to (76.4%), force them to engage in a non-consensual sexual act (14.6%), isolate from others (57.9%), minimize the abuse they experienced (48.7%), or prevent them from speaking out against abuse (53.9%).

Conclusions

This data provides insight into a Muslim cohort’s frequency of sexual burdens which include dysfunction and abuse. Understanding how spiritual abuse can influence patients’ familial, romantic, and sexual relationships may help providers to administer culturally competent care to Muslim patients.

Disclosure

No.
(284) Replacing Malfunctioning Penile Prosthesis
Authors: Majela M , Talib Alzubaidi R , Leiva Ruiz M
Published: March 2024

Introduction

Erectile sexual dysfunction shows a high incidence in the world population. The three-piece penile prosthesis implant has become the standard goal for the surgical correction, showing efficacy, patient satisfaction and a low incidence of complications. Implant malfunction is a cause that often requires a second surgical intervention. Live surgery video is shown showing the technical details of implant replacement in a single surgical procedure.

Objective

show step by step the surgical technique for the replacement of the three-piece penile prosthetic implant.

Methods

Video presentation

Results

The malfunction of the implant is shown during live surgery

Conclusions

Studies are needed to clarify the causes of implant malfunction. Modification of the physical-chemical components of the implant is needed to improve its integrity and durability.

Disclosure

No.
(292) Relationship Between Race, Gleason Score, and Testosterone Levels in Men with Prostate Cancer
Authors: Marciano O , Nordgren R , Raheem O
Published: March 2024

Introduction

It has been known in the literature that Black men are disproportionately affected by prostate cancer in the United States. Various mechanistic pathways have been evaluated including PSA and/or testosterone levels (T) in this at-risk population. Based on prior studies, low PSA is suggested to be predictive of low testosterone independent of prostate cancer pathology. In this study, we aim to evaluate the correlation between race and PSA/T levels in men diagnosed with prostate cancer.

Objective

To further study the relationship between testosterone, PSA, and race in men with prostate cancer.

Methods

An IRB approved database was utilized to obtain values for prostate cancer patients. Prostate cancer patients who had testosterone, PSA, and Gleason scores (GS) were included in our cohort with demographic information. Patients were stratified by PSA category. Low testosterone was defined as T<300 ng/dL, and very low T as 0–200 ng/dL.

Results

In our cohort of 653 prostate cancer patients, the mean age was 66 years. The cohort included 34% African American (AA), 62% White, and 4% other. AA men had a median PSA of 8.0 ng/mL, compared to 0.8 ng/mL in white men (p<0.001). For AA men with GS (8–10) and PSA>4, proportions were: very low T (27%), low T (24%) and normal T (49%). For GS (8–10) and PSA<2, very low T (35%), low T (22%) and normal T (43 %) (p<0.05). For White men with GS (8–10) and PSA>4, very low T (33%), low T (17%) and normal T (50%). For GS (8–10) and PSA<2, very low T (37%), low T (20%) and normal (43%) (p<0.05). In GS (8–10), logistic regression demonstrated neither race nor PSA category were statistically significant predictors of low T.

Conclusions

Our results show that despite significantly higher PSA among AA men with prostate cancer, there was no statistically significant difference in T and GS 8–10 prostate cancer. This finding highlights that racial variation may influence PSA but not GS prostate cancer or T level. Further studies are warranted to elucidate the correlation between PSA and T in higher-risk populations.

Disclosure

No.
Introducing the Condor Array Telescope – IV. A possible nova super-remnant surrounding the putative recurrent nova KT Eridani
Authors: Shara Michael M , Lanzetta Kenneth M , Garland James T , Gromoll Stefan , Valls-Gabaud David , Walter Frederick M , Webb John K , Kniazev Alexei , Townsend Lee , Darnley Matthew J , Healy-Kalesh Michael , Corral-Santana Jesus , Schmidtobreick Linda
Published: March 2024

Just 10 recurrent novae (RNe) – which erupt repeatedly on time-scales shorter than one century – are known in our Galaxy. The most extreme RN known (located in the Andromeda galaxy), M31N 2008-12a, undergoes a nova eruption every year, and is surrounded by a vast nova ‘super-remnant’, 134 pc in extent. Simulations predict that all RNe should be surrounded by similar vast shells, but previous searches have failed to detect them. KT Eri has recently been suggested to be a RN, and we have used the Condor Array Telescope to image its environs through multiple narrow-band filters. We report the existence of a large (∼50-pc diameter), H $\, \alpha$-bright shell centred on KT Eri, exactly as predicted. This strongly supports the claim that KT Eri is the 11th Galactic recurrent nova, and only the second nova known to be surrounded by a super-remnant. SALT spectra of the super-remnant demonstrate that its velocity width is consistent with that of M31-2008-12a.
METTL3 as a master regulator of translation in cancer: mechanisms and implications
Authors: Esteva-Socias Margalida , Aguilo Francesca
Published: March 2024

Translational regulation is an important step in the control of gene expression. In cancer cells, the orchestration of both global control of protein synthesis and selective translation of specific mRNAs promote tumor cell survival, angiogenesis, transformation, invasion and metastasis. N6-methyladenosine (m6A), the most prevalent mRNA modification in higher eukaryotes, impacts protein translation. Over the past decade, the development of m6A mapping tools has facilitated comprehensive functional investigations, revealing the involvement of this chemical mark, together with its writer METTL3, in promoting the translation of both oncogenes and tumor suppressor transcripts, with the impact being context-dependent. This review aims to consolidate our current understanding of how m6A and METTL3 shape translation regulation in the realm of cancer biology. In addition, it delves into the role of cytoplasmic METTL3 in protein synthesis, operating independently of its catalytic activity. Ultimately, our goal is to provide critical insights into the interplay between m6A, METTL3 and translational regulation in cancer, offering a deeper comprehension of the mechanisms sustaining tumorigenesis.
The role of radiotherapy in immunotherapy strategies in the central nervous system
Authors: Gallitto Matthew , Pan Peter C , Chan Michael D , Milano Michael T , Wang Tony J C
Published: March 2024

The clinical efficacy and relative tolerability of adverse effects of immune checkpoint immunotherapy have led to its increasingly routine use in the management of multiple advanced solid malignancies. Radiation therapy (RT) is well-known to have both local and distant immunomodulatory effects, which has led to extensive investigation into the synergism of these 2 therapies. While the central nervous system (CNS) has historically been thought to be a sanctuary site, well-protected by the blood–brain barrier from the effects of immunotherapy, over the last several years studies have shown the benefits of these drugs, particularly in metastatic disease involving the CNS. This review explores current progress and the future of combination therapy with immune checkpoint inhibitors and RT.