bluuebunny/crossref_metadata_2025 huggingface dataset:
Possibilities for the construction of a parallel route of the European transport corridor No 9 through Romania, Bulgaria, and Greece
Authors: Tsonkov Nikolay , Petrov Kamen
Published: December 2023

The Bulgarian state is significantly behind in the development of its strategic road infrastructure. This circumstance is complemented by the deteriorated state of the already-built infrastructure in the Bulgarian state. There is a need to change the policy philosophy for managing and maintaining the strategic infrastructure in Bulgaria. It is necessary to strongly link this policy with the regional development policy, due to the similar objectives they must achieve. They are aimed at bringing Bulgarian regions closer together, and their economic and regional development based on improved connectivity between them. Achieving all this, however, is hampered by a significant deficit in the system. There is a lack of connectivity and development of the transport axes in the North-South direction. In this regard, the authors set as their main objective to analyze and assess the possibilities for the construction of a parallel route of the European transport corridor No. 9 through Romania, Bulgaria, and Greece, which includes the construction of a tunnel between the town of Troyan and the village of Karnare in the central part of the Balkan Mountains. The implementation of this project will bring economic, social, transport, and financial benefits to the Bulgarian state. The construction of the project ensures connectivity between the Balkan countries, the formation of a single European market, stimulating the development of Northern Bulgaria, and a targeted impact on the North and South-Central planning regions.
Road safety impact assessment practices and recommendations
Authors: Popova Vanina
Published: December 2023

This article reviews the practices for conducting Road Safety Impact Assessment (RIA). An overview of current research and methodologies related to this field is presented, and various aspects of the preparation of RSIA are analysed.

The DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL on road infrastructure safety management (RISM Directive) defines the procedure “road safety impact assessment” as a strategic comparative analysis of the impact of a new road or a substantial modification to the existing network on the safety performance of the road network”; The RISM Directive provides only the basic framework for conducting such analysis by just pointing out its basic elements without providing specific methodology for it. Some countries have developed their own methodologies, others not.

Although the RIA is a procedure, that was included in the initial RISM Directive (2008), Bulgaria has not yet had much experience with it, nor has a developed methodology or recommendations for it.

The main aim of this article is to review and analyse international experience in conducting road safety impact assessment and to present some recommendations about it for such procedures from national teams.

The article draws attention to the methods and tools used in the preparation of the RIA. This includes the collection and analysis of road infrastructure and traffic data, the study of previous safety analyses, modelling and simulations of the proposed measures, and the assessment of social and economic aspects.

One of the main aspects discussed in the article is the possibility of using computer models and artificial intelligence (AI) in the preparation of the RIA. AI can be applied to process large volumes of data and perform complex risk and scenario analyses. This allows practitioners to obtain more accurate and predictable results to serve as a basis for making informed road safety decisions.

In conclusion, the article emphasizes the importance of preparing Road safety impact assessment and presents different practices and methodologies that can be used in this process. The use of computer models and AI can improve the efficiency and accuracy of RSIA and contribute to achieving higher standards of road safety.
Purpose of acceleration and deceleration lanes. Comparison of the regulatory framework for the design acceleration and deceleration lanes in Bulgaria, Austria, Germany and the USA (California).
Authors: Zhelev Marin , Nikolov Valentin
Published: December 2023

The report examines and analyzes the purpose of acceleration and deceleration lanes at two-level road interchanges. For the preparation of the current report are used the regulatory framework for the design of acceleration and deceleration lanes from Bulgaria, Austria, Germany and USA – California. The design elements of the acceleration and deceleration lanes are compared in detail. Widths and lengths of lanes, merging zones, angles and slopes. The conclusions of the report are given as guidelines for good practice in the design of road interchanges at one and two levels.
Comment on “Reproducibility study of Monte Carlo simulations for nanoparticle dose enhancement and biological modeling of cell survival curves” by Velten et al [Biomed Phys Eng Express 2023;9:045004]
Authors: Rabus Hans
Published: December 2023

This comment highlights two methodological issues with the recent article by Velten et al [Biomed Phys Eng Express 2023;9:045004]: First, the approach taken in this work with a local effect model (LEM) in 2D leads to a significant overstimation of the number of radiation-induced lesions. This results in order of magnitude smaller predicted survival rates compared to the conventional LEM. Second, the dose without nanoparticles is used as the ‘macroscopic dose’ against which cell survival is plotted. However, for the considered gold concentrations, the average absorbed dose under secondary particle equilibrium is between 2 and 20 times higher with nanoparticles than without.
A fully printed sensor with optical readout for real-time flow monitoring
Authors: Barmpakos Dimitris , Apostolakis Apostolos , Pilatis Aggelos , Pagonis Dimitrios-Nikolaos , Kaltsas Grigoris
Published: December 2023

In recent years, there has been a growing interest in the development of flexible thermal flow sensing devices due to their wide-ranging applications. In this study, we present the fabrication of a screen-printed flow sensor with optical readout on a 125 μm polyethylene terephthalate substrate in a three-layer configuration. The device comprises electrodes made from a commercial silver (Ag) ink, a heating area using a commercial carbon ink, and a thermochromic (TC) layer employing a commercial ink with a standard activation temperature of 31 °C. We designed a specialized experimental setup to evaluate the performance of the optical flow sensor under static and dynamic conditions. To analyze the device’s thermal response and performance across various flow conditions, we utilized a combination of electrical measurements and infrared (IR)-optical imaging techniques. The all-printed device operates on the basis of a thermodynamic cycle frequency, which activates the TC ink, causing it to blink at a frequency related to the flow passing over the sensor. The results of our preliminary testing are highly promising, as the sensor successfully demonstrated a clear relationship between flow and optical duty cycle. This innovative device offers a contactless, low-cost, easy-to-use flow detection method and holds significant potential for various practical applications.
Drug–drug interaction prediction: databases, web servers and computational models
Authors: Zhao Yan , Yin Jun , Zhang Li , Zhang Yong , Chen Xing
Published: December 2023

In clinical treatment, two or more drugs (i.e. drug combination) are simultaneously or successively used for therapy with the purpose of primarily enhancing the therapeutic efficacy or reducing drug side effects. However, inappropriate drug combination may not only fail to improve efficacy, but even lead to adverse reactions. Therefore, according to the basic principle of improving the efficacy and/or reducing adverse reactions, we should study drug–drug interactions (DDIs) comprehensively and thoroughly so as to reasonably use drug combination. In this review, we first introduced the basic conception and classification of DDIs. Further, some important publicly available databases and web servers about experimentally verified or predicted DDIs were briefly described. As an effective auxiliary tool, computational models for predicting DDIs can not only save the cost of biological experiments, but also provide relevant guidance for combination therapy to some extent. Therefore, we summarized three types of prediction models (including traditional machine learning-based models, deep learning-based models and score function-based models) proposed during recent years and discussed the advantages as well as limitations of them. Besides, we pointed out the problems that need to be solved in the future research of DDIs prediction and provided corresponding suggestions.
Coracle—a machine learning framework to identify bacteria associated with continuous variables
Authors: Staab Sebastian , Cardénas Anny , Peixoto Raquel S , Schreiber Falk , Voolstra Christian R
Published: December 2023

We present Coracle, an artificial intelligence (AI) framework that can identify associations between bacterial communities and continuous variables. Coracle uses an ensemble approach of prominent feature selection methods and machine learning (ML) models to identify features, i.e. bacteria, associated with a continuous variable, e.g. host thermal tolerance. The results are aggregated into a score that incorporates the performances of the different ML models and the respective feature importance, while also considering the robustness of feature selection. Additionally, regression coefficients provide first insights into the direction of the association. We show the utility of Coracle by analyzing associations between bacterial composition data (i.e. 16S rRNA Amplicon Sequence Variants, ASVs) and coral thermal tolerance (i.e. standardized short-term heat stress-derived diagnostics). This analysis identified high-scoring bacterial taxa that were previously found associated with coral thermal tolerance. Coracle scales with feature number and performs well with hundreds to thousands of features, corresponding to the typical size of current datasets. Coracle performs best if run at a higher taxonomic level first (e.g. order or family) to identify groups of interest that can subsequently be run at the ASV level.

Availability and implementation

Coracle can be accessed via a dedicated web server that allows free and simple access: http://www.micportal.org/coracle/index. The underlying code is open-source and available via GitHub https://github.com/SebastianStaab/coracle.git.
Cross-frequency and inter-regional phase synchronization in explicit transitive inference
Authors: Heldmann Marcus , Rohde Lisa Suzanna , Münte Thomas F , Ye Zheng
Published: December 2023

Explicit logical reasoning, like transitive inference, is a hallmark of human intelligence. This study investigated cortical oscillations and their interactions in transitive inference with EEG. Participants viewed premises describing abstract relations among items. They accurately recalled the relationship between old pairs of items, effectively inferred the relationship between new pairs of items, and discriminated between true and false relationships for new pairs. First, theta (4–7 Hz) and alpha oscillations (8–15 Hz) had distinct functional roles. Frontal theta oscillations distinguished between new and old pairs, reflecting the inference of new information. Parietal alpha oscillations changed with serial position and symbolic distance of the pairs, representing the underlying relational structure. Frontal alpha oscillations distinguished between true and false pairs, linking the new information with the underlying relational structure. Second, theta and alpha oscillations interacted through cross-frequency and inter-regional phase synchronization. Frontal theta-alpha 1:2 phase locking appeared to coordinate spectrally diverse neural activity, enhanced for new versus old pairs and true versus false pairs. Alpha-band frontal-parietal phase coherence appeared to coordinate anatomically distributed neural activity, enhanced for new versus old pairs and false versus true pairs. It suggests that cross-frequency and inter-regional phase synchronization among theta and alpha oscillations supports human transitive inference.
Abnormal white and gray matter functional connectivity is associated with cognitive dysfunction in presbycusis
Authors: Wang Yao , Gao Yuting , Zhao Min , Hu Xin , Wang Jing , Han Yu , Wang Qinghui , Fu Xinxing , Dai Zongrui , Ren Funxin , Li Muwei , Gao Fei
Published: December 2023

Presbycusis is characterized by high-frequency hearing loss and is closely associated with cognitive decline. Previous studies have observed functional reorganization of gray matter in presbycusis, but the information transmission between gray matter and white matter remains ill-defined. Using resting-state functional magnetic resonance imaging, we investigated differences in functional connectivity (GM-GM, WM-WM, and GM-WM) between 60 patients with presbycusis and 57 healthy controls. Subsequently, we examined the correlation between these connectivity differences with high-frequency hearing loss as well as cognitive impairment. Our results revealed significant alterations in functional connectivity involving the body of the corpus callosum, posterior limbs of the internal capsule, retrolenticular region of the internal capsule, and the gray matter regions in presbycusis. Notably, disrupted functional connectivity was observed between the body of the corpus callosum and ventral anterior cingulate cortex in presbycusis, which was associated with impaired attention. Additionally, enhanced functional connectivity was found in presbycusis between the internal capsule and the ventral auditory processing stream, which was related to impaired cognition in multiple domains. These two patterns of altered functional connectivity between gray matter and white matter may involve both bottom-up and top-down regulation of cognitive function. These findings provide novel insights into understanding cognitive compensation and resource redistribution mechanisms in presbycusis.
Effect of Daily Vitamin D Supplementation on Risk of Upper Respiratory Infection in Older Adults: A Randomized Controlled Trial
Authors: Camargo Carlos A , Schaumberg Debra A , Friedenberg Georgina , Dushkes Rimma , Glynn Robert J , Gold Diane R , Mora Samia , Lee I Min , Buring Julie E , Manson JoAnn E
Published: December 2023

Background

Among individuals with vitamin D deficiency, daily vitamin D supplementation appears to lower risk of acute respiratory infection. However, recent trials, in different populations and using different regimens, have yielded null results. We investigated the effect of daily vitamin D supplementation (vs placebo) on risk of upper respiratory infection (URI) in older adults.

Methods

The VITamin D and OmegA-3 TriaL (VITAL) is a randomized, double-blind, placebo-controlled trial of supplemental vitamin D and/or omega-3 fatty acids in generally healthy men (age ≥50 years) and women (age ≥55 years). This prespecified analysis focuses on vitamin D3 (2000 IU/day) versus placebo in the 15 804 (61%) participants with baseline serum total 25-hydroxyvitamin D level. The primary outcome was self-report of a recent URI at 1-year follow-up.

Results

Participants had a mean age of 68 years and 51% were women; 76% were non-Hispanic White, 16% Black, and 8% other race/ethnicity. The mean 25-hydroxyvitamin D level at baseline was 31 (standard deviation, 10) ng/mL, with <12 ng/mL in 2.4%. The overall effect of vitamin D supplementation on recent URI was nonsignificant (odds ratio [OR], 0.96 [95% confidence interval {CI}, .86–1.06]). In the prespecified subgroup of primary interest (<12 ng/mL and denied taking concurrent vitamin D), which had only 255 participants, vitamin D supplementation was nonsignificant (OR, 0.60 [95% CI, .28–1.30]). Statistical power to assess effect modification in other subgroups was limited.

Conclusions

In older adults not selected for vitamin D deficiency, supplemental vitamin D did not lower URI risk overall. Whether effects differ in subgroups requires further study.

Clinical Trials Registration. NCT01169259.
Outcomes and Endpoints of Postoperative Recurrence in Crohn’s Disease: Systematic Review and Consensus Conference
Authors: Hammoudi Nassim , Sachar David , D’Haens Geert , Reinisch Walter , Kotze Paulo Gustavo , Vermeire Severine , Schölmerich Jürgen , Kamm Michael A , Griffiths Anne , Panes Julian , Ghosh Subrata , Siegel Corey A , Bemelman Willem , O’Morain Colm , Steinwurz Flavio , Fleshner Phillip , Mantzaris Gerassimos J , Sands Bruce , Abreu Maria T , Dotan Iris , Turner Dan , Dignass Axel , Allez Matthieu
Published: December 2023

Background

Outcomes after ileocolonic resection in Crohn’s disease [CD] are heterogeneous, and a clear definition of postoperative recurrence remains to be determined. Our Endpoints Working Group of the International Organization for the study of Inflammatory Bowel Disease [IOIBD] aimed to standardise postoperative outcomes, to discuss which endpoints should be used for postoperative clinical trials, and to define those which could be used in trials or registries.

Methods

Based on a systematic review of the literature, recommendations and statements were drafted and sent to all IOIBD members for a first round of voting. Recommendations and statements were revised based on the voters’ comments during a consensus hybrid conference open to all IOIBD members. If no agreement was reached after two rounds of voting, the statement was excluded.

Results

In the systematic review, 3071 manuscripts were screened of which 434 were included. Sixteen recommendations were identified, of which 11 were endorsed. Recommendations and statements include that endoscopy remains the gold standard and should be used as a short-term primary endpoint in both observational cohorts and randomised controlled trials. Clinical symptoms classically used in clinical trials for luminal CD are not reliable in this specific situation. For that reason, longer-term endpoints should be based on the evidence of macroscopic inflammation assessed by imaging techniques, endoscopy, or as reflected by the presence of complications.

Conclusions

Agencies recommend the use of clinical evaluations, as in the case of luminal CD, and do not recognise primary endpoints based solely on endoscopy. This consensus has led to agreement on the need to define postoperative endoscopy-based and/or imaging-based endpoints.
Impact of smoking initiation age on nicotine dependency and cardiovascular risk factors: a retrospective cohort study in Japan
Authors: Mittal Swati , Komiyama Maki , Ozaki Yuka , Yamakage Hajime , Satoh-Asahara Noriko , Wada Hiromichi , Yasoda Akihiro , Funamoto Masafumi , Katanasaka Yasufumi , Sunagawa Yoichi , Morimoto Tatsuya , Akao Masaharu , Abe Mitsuru , Takahashi Yuko , Nakayama Takeo , Hasegawa Koji
Published: December 2023

Aims

Initiating smoking in early adolescence results in challenges with smoking cessation and is associated with high risk of cardiovascular disease. Recently, the initiation of smoking has transitioned from adolescence to young adulthood. However, there are few reports on the impact of initiating smoking at a later age. This study investigated the impact of the age of smoking initiation on nicotine dependency, smoking cessation rates, and cardiovascular risk factors, using a cut-off point of 20 years, within the Japanese population.

Methods and results

This retrospective cohort study encompassed 1382 smokers who sought smoking cessation treatment at Kyoto Medical Centre Hospital between 2007 and 2019. Clinical indicators were evaluated by adjusting for age at the time of hospital visit and sex. The smoking cessation rate was further adjusted for treatment medication. The group with a smoking initiation age of <20 years reported a higher number of cigarettes/day (P = 0.002), higher respiratory carbon monoxide levels (P < 0.001), a higher Fagerström Test for Nicotine Dependence (FTND) score (P < 0.001), and a higher Self-rating Depression Scale score (P = 0.014). They also reported lower diastolic blood pressure (P = 0.020) and a lower successful smoking cessation rate [odds ratio: 0.736, 95% confidence interval (0.569, 0.951)] than the group with a smoking initiation age of ≥20 years. When smokers were divided into four groups based on the age they started smoking, the FTND score for those who started at 20–21 years was significantly higher than the score for those who started at 22 years or older.

Conclusion

In young adulthood, initiating smoking later (beyond 20 years old) was associated with lower nicotine dependency and fewer depressive tendencies, as well as a higher success rate in smoking cessation among Japanese smokers. The results might suggest that raising the legal smoking initiation age from 20 to 22 years old or older could be effective in reducing nicotine dependency in smokers.
Job displacement and reallocation failure. Evidence from climate shocks in Morocco
Authors: Alfani Federica , Molini Vasco , Pallante Giacomo , Palma Alessandro
Published: December 2023

We investigate the impact of severe drought shocks in Morocco’s agricultural sector. Using a staggered difference-in-differences design, we estimate that climatic shocks resulted in a job displacement of approximately 6.5 percentage points for workers exposed to severe drought events. Additionally, we observe that, overall, approximately 39 per cent of these workers remained unemployed, leading to a partial reallocation failure. These effects are significant only for severe and extreme shocks, persist for at least 5 years, and are more pronounced among informal and female workers.
Metabolic syndrome and poor self-rated health as risk factors for premature employment exit: a longitudinal study among 55 016 middle-aged and older workers from the Lifelines Cohort Study and Biobank
Authors: Runge Katharina , van Zon Sander K R , Henkens Kène , Bültmann Ute
Published: December 2023

Background

Poor self-rated health (SRH) is a well-established risk factor for premature employment exit through unemployment, work disability, and early retirement. However, it is unclear whether the premature employment exit risk associated with underlying cardio-metabolic health conditions is fully captured by poor SRH. This study examines the metabolic syndrome (MetS), an early-stage risk factor for cardiovascular disease and type two diabetes mellitus, as a risk factor for premature employment exit while controlling for poor SRH.

Methods

We analyzed data from N = 55 016 Dutch workers (40–64 years) from five waves of the Lifelines Cohort Study and Biobank. MetS components were based on physical measures, blood markers, and medication use. SRH and employment states were self-reported. The associations between MetS, SRH, and premature employment exit types were analyzed using competing risk regression analysis.

Results

During 4.3 years of follow-up, MetS remained an independent risk factor for unemployment [adjusted subdistribution hazard ratio (SHR): 1.14, 95% CI: 1.03, 1.25] and work disability (adjusted SHR: 1.33, 95% CI: 1.11, 1.58) when adjusted for poor SRH, common chronic diseases related to labor market participation (i.e., cancer, musculoskeletal-, pulmonary-, and psychiatric diseases), and sociodemographic factors. MetS was not associated with early retirement.

Conclusions

Poor SRH did not fully capture the risk for unemployment and work disability associated with MetS. More awareness about MetS as a ‘hidden’ cardio-metabolic risk factor for premature employment exit is needed among workers, employers, and occupational health professionals. Regular health check-ups including MetS assessment and MetS prevention might help to prolong healthy working lives.
Gigantic animal cells suggest organellar scaling mechanisms across a 50-fold range in cell volume
Authors: Adams Alexander Nichols , Smith Bradford Julian , Raad Thomas John , Mueller Rachel Lockridge
Published: December 2023

The largest cells are orders of magnitude bigger than the smallest cells. Organelle content scales to maintain cell function, with different organelles increasing in volume, length, or number as cells increase in size. Scaling may also reflect functional demands placed on organelles by increased cell size. Amphibians exhibit exceptional diversity in cell size. Using transmission electron microscopy, we analyzed 3 species whose enterocyte cell volumes range from 228 to 10,593 μm3. We show that nuclear volume increases by an increase in radius while mitochondrial volume increases by an increase in total network length; the endoplasmic reticulum and Golgi apparatus, with their complex shapes, are intermediate. Notably, all 4 organelle types increase in total volume proportional to cell volume, despite variation in functional (i.e., metabolic, transport) demands. This pattern suggests that organellar building blocks are incorporated into more or larger organelles following the same rules across species that vary ~50-fold in cell sizes, consistent with a “limited precursor” model for organellar scaling that, in turn, assumes equivalent cytoplasmic concentrations of organellar building block proteins. Taken together, our results lead us to hypothesize that salamanders have evolved increased biosynthetic capacity to maintain functional protein concentrations despite huge cell volumes.
Seasonality in land–ocean connectivity and local processes control sediment bacterial community structure and function in a High Arctic tidal flat
Authors: Handler Eleanor R , Andersen Sebastian D J , Gradinger Rolf , McGovern Maeve , Vader Anna , Poste Amanda E
Published: December 2023

Climate change is altering patterns of precipitation, cryosphere thaw, and land–ocean influxes, affecting understudied Arctic estuarine tidal flats. These transitional zones between terrestrial and marine systems are hotspots for biogeochemical cycling, often driven by microbial processes. We investigated surface sediment bacterial community composition and function from May to September along a river–intertidal–subtidal–fjord gradient. We paired metabarcoding of in situ communities with in vitro carbon-source utilization assays. Bacterial communities differed in space and time, alongside varying environmental conditions driven by local seasonal processes and riverine inputs, with salinity emerging as the dominant structuring factor. Terrestrial and riverine taxa were found throughout the system, likely transported with runoff. In vitro assays revealed sediment bacteria utilized a broader range of organic matter substrates when incubated in fresh and brackish water compared to marine water. These results highlight the importance of salinity for ecosystem processes in these dynamic tidal flats, with the highest potential for utilization of terrestrially derived organic matter likely limited to tidal flat areas (and times) where sediments are permeated by freshwater. Our results demonstrate that intertidal flats must be included in future studies on impacts of increased riverine discharge and transport of terrestrial organic matter on coastal carbon cycling in a warming Arctic.
Genomic Tools in Biological Invasions: Current State and Future Frontiers
Authors: McGaughran Angela , Dhami Manpreet K , Parvizi Elahe , Vaughan Amy L , Gleeson Dianne M , Hodgins Kathryn A , Rollins Lee A , Tepolt Carolyn K , Turner Kathryn G , Atsawawaranunt Kamolphat , Battlay Paul , Congrains Carlos , Crottini Angelica , Dennis Tristan P W , Lange Claudia , Liu Xiaoyue P , Matheson Paige , North Henry L , Popovic Iva , Rius Marc , Santure Anna W , Stuart Katarina C , Tan Hui Zhen , Wang Cui , Wilson Jonathan
Published: December 2023

Human activities are accelerating rates of biological invasions and climate-driven range expansions globally, yet we understand little of how genomic processes facilitate the invasion process. Although most of the literature has focused on underlying phenotypic correlates of invasiveness, advances in genomic technologies are showing a strong link between genomic variation and invasion success. Here, we consider the ability of genomic tools and technologies to (i) inform mechanistic understanding of biological invasions and (ii) solve real-world issues in predicting and managing biological invasions. For both, we examine the current state of the field and discuss how genomics can be leveraged in the future. In addition, we make recommendations pertinent to broader research issues, such as data sovereignty, metadata standards, collaboration, and science communication best practices that will require concerted efforts from the global invasion genomics community.
Negative Selection on a SOD1 Mutation Limits Canine Degenerative Myelopathy While Avoiding Inbreeding
Authors: Ukawa Hisashi , Akiyama Noriyoshi , Yamamoto Fumiko , Ohashi Ken , Ishihara Genki , Matsumoto Yuki
Published: December 2023

Several hundred disease-causing mutations are currently known in domestic dogs. Breeding management is therefore required to minimize their spread. Recently, genetic methods such as direct-to-consumer testing have gained popularity; however, their effects on dog populations are unclear. Here, we aimed to evaluate the influence of genetic testing on the frequency of mutations responsible for canine degenerative myelopathy and assess the changes in the genetic structure of a Pembroke Welsh corgi population from Japan. Genetic testing of 5,512 dogs for the causative mutation in superoxide dismutase 1 (SOD1) (c.118G>A (p.E40K)) uncovered a recent decrease in frequency, plummeting from 14.5% (95/657) in 2019 to 2.9% (24/820) in 2022. Weir and Cockerham population differentiation (FST) based on genome-wide single-nucleotide polymorphism (SNP) of 117 selected dogs detected the SNP with the highest FST located in the intron of SOD1 adjacent to the c.118G>A mutation, supporting a selection signature on SOD1. Further genome-wide SNP analyses revealed no obvious changes in inbreeding levels and genetic diversity between the 2019 and 2022 populations. Our study highlights that genetic testing can help inform improved mating choices in breeding programs to reduce the frequency of risk variants and avoid inbreeding. This combined strategy could decrease the genetic risk of canine degenerative myelopathy, a fatal disease, within only a few years.
Exploring the Intersectionality of Place and Gender Among Older Adults in Ghana: An Examination of Women’s Disability Disadvantage
Authors: Burns Shane D , Best Latrica E , Amoatey Solomon
Published: December 2023

Background and Objectives

Ghana’s older adult population is growing rapidly and is projected to double by 2050. It is well-documented that social, health, and housing factors influence segmented aging trajectories that lead to disparate rates of disability. However, little is known about how the intersection of place (i.e., urban and rural) and gender (i.e., woman and man) inform rates of disability among older Ghanaians. We seek to examine this gap in the literature through an intersectional approach.

Research Design and Methods

Using logistic regression with Wave 1 (2007/2008) data from the World Health Organization’s Study on global AGEing and adult health (SAGE) Ghana, we investigate the prevalence of reporting activities of daily living (ADL) disability among respondents ages 50+ (n = 4,106). To document gender differences by place, we compute separate adjusted odds ratio models among urban and rural respondents. We also control for health, social, and housing factors that might explain gender differences.

Results

Compared to urban men, urban women’s ADL disability disadvantage was explained by marital status, particularly widowhood. In contrast, rural women consistently reported an ADL disability disadvantage when compared to rural men. Additionally, we found that the morbidity profiles of those who reported ADL disability differed by place and that certain ADL difficulties (i.e., bed transferring and toileting) were especially common among women respondents.

Discussion and Implications

Women, regardless of urban or rural residence, were especially vulnerable to ADL disability. Marital status, particularly widows, explained the difference in disability risk between urban men and urban women. This finding suggests that urban women’s risk of ADL disability is attenuated during the partnership. Also, we speculate that varied morbidity associations with ADL disability are due to different stressors in urban versus rural environments. These findings also generate further interest in about rural women’s disability disadvantage.
DrugSim2DR: systematic prediction of drug functional similarities in the context of specific disease for drug repurposing
Authors: Wu Jiashuo , Li Ji , He Yalan , Huang Junling , Zhao Xilong , Pan Bingyue , Wang Yahui , Cheng Liang , Han Junwei
Published: December 2023

Background

Traditional approaches to drug development are costly and involve high risks. The drug repurposing approach can be a valuable alternative to traditional approaches and has therefore received considerable attention in recent years.

Findings

Herein, we develop a previously undescribed computational approach, called DrugSim2DR, which uses a network diffusion algorithm to identify candidate anticancer drugs based on a drug functional similarity network. The innovation of the approach lies in the drug–drug functional similarity network constructed in a manner that implicitly links drugs through their common biological functions in the context of a specific disease state, as the similarity relationships based on general states (e.g., network proximity or Jaccard index of drug targets) ignore disease-specific molecular characteristics. The drug functional similarity network may provide a reference for prediction of drug combinations. We describe and validate the DrugSim2DR approach through analysis of data on breast cancer and lung cancer. DrugSim2DR identified some US Food and Drug Administration–approved anticancer drugs, as well as some candidate drugs validated by previous studies in the literature. Moreover, DrugSim2DR showed excellent predictive performance, as evidenced by receiver operating characteristic analysis and multiapproach comparisons in various cancer datasets.

Conclusions

DrugSim2DR could accurately assess drug–drug functional similarity within a specific disease context and may more effectively prioritize disease candidate drugs. To increase the usability of our approach, we have developed an R-based software package, DrugSim2DR, which is freely available on CRAN (https://CRAN.R-project.org/package=DrugSim2DR).
The quality of telemedicine consultations for sexually transmitted infections in China
Authors: Si Yafei , Xue Hao , Liao Huipeng , Xie Yewei , Xu Dong (Roman) , Smith M Kumi , Yip Winnie , Cheng Weibin , Tian Junzhang , Tang Weiming , Sylvia Sean
Published: December 2023

The burden of sexually transmitted infections (STIs) continues to increase in developing countries like China, but the access to STI care is often limited. The emergence of direct-to-consumer (DTC) telemedicine offers unique opportunities for patients to directly access health services when needed. However, the quality of STI care provided by telemedicine platforms remains unknown. After systemically identifying the universe of DTC telemedicine platforms providing on-demand consultations in China in 2019, we evaluated their quality using the method of unannounced standardized patients (SPs). SPs presented routine cases of syphilis and herpes. Of the 110 SP visits conducted, physicians made a correct diagnosis in 44.5% (95% CI: 35.1% to 54.0%) of SP visits, and correctly managed 10.9% (95% CI: 5.0% to 16.8%). Low rates of correct management were primarily attributable to the failure of physicians to refer patients for STI testing. Controlling for other factors, videoconference (vs SMS-based) consultation mode and the availability of public physician ratings were associated with higher-quality care. Our findings suggest a need for further research on the causal determinants of care quality on DTC telemedicine platforms and effective policy approaches to promote their potential to expand access to STI care in developing countries while limiting potential unintended consequences for patients.
A 49-bp deletion of PmAP2L results in a double flower phenotype in Prunus mume
Authors: Liu Weichao , Zheng Tangchun , Qiu Like , Guo Xiaoyu , Li Ping , Yong Xue , Li Lulu , Ahmad Sagheer , Wang Jia , Cheng Tangren , Zhang Qixiang
Published: December 2023

The double flower is an important trait with substantial ornamental value. While mutations in PETALOSA TOE-type or AG (AGAMOUS) genes play a crucial role in enhancing petal number in ornamental plants, the complete mechanism underlying the formation of double flowers remains to be fully elucidated. Through the application of bulked segregant analysis (BSA), we identified a novel gene, APETALA2-like (PmAP2L), characterized by a 49-bp deletion in double-flowered Prunus mume. β-Glucuronidase (GUS) staining and luciferase reporter assays confirmed that the 49-bp deletion in PmAP2L reduced its binding with Pmu-miRNA172a. Phylogenetic analysis and microsynteny analysis suggested that PmAP2L was not a PETALOSA TOE-type gene, and it might be a new gene controlling the formation of double flower in P. mume. Subsequently, overexpression of PmAP2L-D in tobacco led to a significant rise in the number of stamens and the conversion of stamens to petals. Furthermore, silencing of the homologue of RC5G0530900 in rose significantly reduced the number of petals. Using transient gene expression in P. mume flower buds, we determined the functional differences between PmAP2L-D and PmAP2-S in controlling flower development. Meanwhile, DNA-affinity purification sequencing (DAP-seq), yeast hybrid assays and luciferase reporter assays indicated that PmAP2L negatively regulated the floral organ identity genes by forming a repressor complex with PmTPL and PmHDA6/19. Overall, these findings indicate that the variation in PmAP2L is associated with differences in the regulation of genes responsible for floral organ identity, providing new insights into the double-flower trait and double-flower breeding in plants.
Deciphering the intricate hierarchical gene regulatory network: unraveling multi-level regulation and modifications driving secondary cell wall formation
Authors: Wei Zhigang , Wei Hairong
Published: December 2023

Wood quality is predominantly determined by the amount and the composition of secondary cell walls (SCWs). Consequently, unraveling the molecular regulatory mechanisms governing SCW formation is of paramount importance for genetic engineering aimed at enhancing wood properties. Although SCW formation is known to be governed by a hierarchical gene regulatory network (HGRN), our understanding of how a HGRN operates and regulates the formation of heterogeneous SCWs for plant development and adaption to ever-changing environment remains limited. In this review, we examined the HGRNs governing SCW formation and highlighted the significant key differences between herbaceous Arabidopsis and woody plant poplar. We clarified many confusions in existing literatures regarding the HGRNs and their orthologous gene names and functions. Additionally, we revealed many network motifs including feed-forward loops, feed-back loops, and negative and positive autoregulation in the HGRNs. We also conducted a thorough review of post-transcriptional and post-translational aspects, protein–protein interactions, and epigenetic modifications of the HGRNs. Furthermore, we summarized how the HGRNs respond to environmental factors and cues, influencing SCW biosynthesis through regulatory cascades, including many regulatory chains, wiring regulations, and network motifs. Finally, we highlighted the future research directions for gaining a further understanding of molecular regulatory mechanisms underlying SCW formation.
A surgically salvaged case: emergency Root-Commando procedure for infective endocarditis and chronic dissecting aneurysm of the sinus of Valsalva
Authors: Nosaka Yu , Kato Hiroki , No Hironari
Published: December 2023

The Commando procedure for infective endocarditis is a high-risk intervention. However, infective endocarditis involving the intervalvular fibrosa is fatal in the absence of surgery. A 41-year-old man with no medical history visited a doctor with chest pain and dyspnoea. Ascending aortic dissection and vegetation on the mitral valve were noted on echocardiography, so he was transferred to our hospital. The diagnosis was dissecting aneurysm of the sinus of Valsalva and acute heart failure due to aortic regurgitation, mitral regurgitation and infective endocarditis. We decided on emergency surgery. Intraoperatively, we confirmed abscess extending to the left atrial roof and destruction of the intervalvular fibrosa, so we performed the Root-Commando procedure. The patient was saved and discharged 47 days after transfer to our hospital through the reoperation on postoperative day 30.
Epidemiology, clinical outcomes and risk factors of third-generation cephalosporin-resistant Escherichia coli hospitalized infections in remote Australia—a case–control study
Authors: Camilleri Shayne , Tsai Danny , Langham Freya , Ullah Shahid , Chiong Fabian
Published: December 2023

Background

Incidence of third-generation cephalosporin-resistant (3GCR) Escherichia coli infections has increased in remote Australia from 2012 to 2018.

Objectives

To describe the epidemiology of 3GCR E. coli in Central Australia.

Methods

A case–control study was conducted in the primary Central Australian hospital. Patient characteristics, antibiotic usage and clinical outcomes were compared between adult hospitalizations with 3GCR and susceptible E. coli isolates in 2018–19. Poisson regression was used to compare the incidence of 3GCR hospitalizations between Indigenous and non-Indigenous individuals. Patient characteristics and antibiotic usage were tested for associations with 3GCR isolates using univariate analysis.

Results

A total of 889 E. coli isolates were identified, of which 187 (21%) were 3GCR. The incidence of 3GCR E. coli infection was 2.15 per 1000 person-years, with an incidence rate ratio of 6.8 (95% CI 4.6–10.1) between Indigenous and non-Indigenous individuals. When compared with the control group, 3GCR E. coli infections were associated with a higher Charlson comorbidity index (CCI ≥3 in 30.7% versus 15.0%, P < 0.001) and were more commonly healthcare associated (52.4% versus 26.7%, P < 0.001). A higher 1 year mortality was observed in the 3GCR group after adjustment for comorbidity (OR = 4.43, P = 0.002), but not at 30 days (2.4% versus 0.0%, P = 0.2). The 3GCR group used more antibiotics in the past 3 months (OR = 5.75, P < 0.001) and 12 months (OR = 3.65, P < 0.001).

Conclusions

3GCR E. coli infections in remote Australia disproportionally affect Indigenous peoples and are associated with a high burden of comorbidities and antibiotic use. Strategies to enhance antimicrobial stewardship should be considered in this remote setting.
Patient-Centric Quantitative Microsampling for Accurate Determination of Urine Albumin to Creatinine Ratio (UACR) in a Clinical Setting
Authors: Löfgren Lars , von Euler Chelpin Marianne , Bhat Maria , Althage Magnus , Hober Andreas , Edfors Fredrik , Ruckh Tim , Challis Benjamin , Davidsson Pia , Miliotis Tasso
Published: December 2023

Background

Developing and implementing new patient-centric strategies for drug trials lowers the barrier to participation for some patients by reducing the need to travel to research sites. In early chronic kidney disease (CKD) trials, albuminuria is the key measure for determining treatment effect prior to pivotal kidney outcome trials.

Methods

To facilitate albuminuria sample collection outside of a clinical research site, we developed 2 quantitative microsampling methods to determine the urinary albumin to creatinine ratio (UACR). Readout was performed by LC-MS/MS.

Results

For the Mitra device the within-batch precision (CV%) was 2.8% to 4.6% and the between-batch precision was 5.3% to 6.1%. Corresponding data for the Capitainer device were 4.0% to 8.6% and 6.7% to 9.0%, respectively. The storage stability at room temperature for 3 weeks was 98% to 103% for both devices. The recovery for the Mitra and Capitainer devices was 104% (SD 7.0%) and 95 (SD 7.4%), respectively. The inter-assay comparison of UACR assessment generated results that were indistinguishable regardless of microsampling technique. The accuracy based on LC-MS/MS vs analysis of neat urine using a clinical chemistry analyzer was assessed in a clinical setting, resulting in 102 ± 8.0% for the Mitra device and 95 ± 10.0% for the Capitainer device.

Conclusions

Both UACR microsampling measurements exhibit excellent accuracy and precision compared to a clinical chemistry analyzer using neat urine. We applied our patient-centric sampling strategy to subjects with heart failure in a clinical setting. Precise UACR measurements using quantitative microsampling at home would be beneficial in clinical drug development for kidney therapies.
Standing up to problematic content on social media: which objection strategies draw the audience’s approval?
Authors: Zhao Pengfei , Bazarova Natalie N , DiFranzo Dominic , Hui Winice , Kizilcec René F , Margolin Drew
Published: December 2023

Problematic content on social media can be countered through objections raised by other community members. While intended to deter offenses, objections can influence the surrounding audience observing the interaction, leading to their collective approval or disapproval. The results of an experiment manipulating seven types of objections against common types of offenses indicate audiences’ support for objections that implore via appeals and disapproval of objections that threaten the offender, as they view the former as more moral, appropriate, and effective compared to the latter. Furthermore, audiences tend to prefer more benign and less threatening objections regardless of the offense severity (following the principle of “taking the high road”) instead of objections proportionate to the offense (“an eye for an eye”). Taken together, these results show how objections to offensive behaviors may impact collective perceptions on social media, paving the way for interventions to foster effective objection strategies in social media discussions.
Reliability assessment of methylthioadenosine phosphorylase immunohistochemistry as a surrogate biomarker for CDKN2A homozygous deletion in adult-type IDH-mutant diffuse gliomas
Authors: Gundogdu Fatma , Babaoglu Berrin , Soylemezoglu Figen
Published: December 2023

According to the 2021 World Health Organization classification of brain tumors, astrocytomas containing a CDKN2A/B homozygous deletion (HD) are designated as grade 4 even when no microvascular proliferation and/or necrosis is present. In this study, we aimed to investigate the relationship between CDKN2A HD and loss of methylthioadenosine phosphorylase (MTAP) expression in adult-type IDH-mutant gliomas and to assess the sensitivity and specificity of MTAP immunohistochemistry (IHC) along with interobserver agreement as a surrogate biomarker for CDKN2A HD. Eighty-eight astrocytomas and 71 oligodendrogliomas cases that were diagnosed between 2014 and 2021 at Hacettepe University were selected and tissue microarrays were conducted to perform CDKN2A fluorescence in situ hybridization and MTAP IHC. Twenty-five (15.7%) cases harbored CDKN2A HD. MTAP loss was detected in 28 (15.7%) cases by the first observer and 27 (17%) cases by the second observer. The sensitivity and specificity of MTAP were calculated as 88% and 95.52%-96.27% for 2 observers. A very good/perfect agreement was noted between the observers (Cohen kappa coefficient = 0.938). Intratumoral heterogeneity was observed in 4 cases. MTAP IHC was found to be a reliable surrogate biomarker as a possible alternative to CDKN2A HD identification with a high sensitivity and specificity along with high interobserver agreement.