bluuebunny/crossref_metadata_2025 huggingface dataset:
Routine Data Analysis of HIV Pre-Exposure Prophylaxis Use and Rates of Sexually Transmitted Infections Since Coverage of HIV Pre-Exposure Prophylaxis by the Statutory Health Insurance in Germany
Authors: Valbert Frederik , Schmidt Daniel , Kollan Christian , Dröge Patrik , Klein Melanie , Schneider Udo , Friebe Martin , Wasem Jürgen , Neumann Anja
Published: August 2024

Human immunodeficiency virus pre-exposure prophylaxis (PrEP) is considered as an effective protection against a human immunodeficiency virus (HIV) infection. However, it is still unclear, how PrEP use is associated with the incidence of sexually transmitted infections (STI) other than HIV. PrEP became reimbursable in Germany from September 1, 2019 for persons with statutory health insurance (SHI). With the EvE-PrEP study, the Federal Ministry of Health commissioned the evaluation of the effects of the new reimbursement situation in Germany. In the presented module of the EvE-PrEP study, routine data from three large German SHI funds were analyzed in anonymized form for the period January 1, 2019 to March 31, 2020. Data were analyzed regarding: Characteristics and adherence of PrEP users, treatment success of PrEP, and changes in STI incidence rates before and since PrEP use. The cooperating SHI funds collectively covered about 52% of the overall population in Germany in 2019. A total of 7102 persons with PrEP use were included into the analysis. These were predominantly male (99%), on average 37.4 years old and a high proportion of persons lived in large cities. The average quotient of PrEP daily defined doses and assumed days on PrEP was 87%. The average STI rates normalized per 100 person-years at individual level pre PrEP did not statistically significant differ compared to since PrEP (chlamydia: 17.5 vs. 17.6, gonococcal infection: 29.1 vs. 30.7, and syphilis: 14.6 vs.13.6). A large data set was used to evaluate the introduction of PrEP as a SHI benefit in Germany. A potentially suspected increase in bacterial STI incidence rates was not found. A rather high average adherence rate was observed. The very high proportion of men and people from the largest German cities among PrEP users is striking. These results could indicate barriers to PrEP access for people at risk of HIV, especially if they are women or people living in less urban areas.
Avenues for Coexistence: How Perception of Costs and Benefits Shape Attitudes towards Wolves
Authors: Lino Sofia , Carvalho João , Fonseca Carlos , Rosalino Luís Miguel
Published: August 2024

Human dimensions play a pivotal role in wolf management and conservation. To offer an informed basis to improve Human-Wolf coexistence, we explore how socio-demographic factors, fear, knowledge, and perceptions of costs and benefits of wolf presence drive human attitudes in the southern area of the Douro River, Portugal, a region inhabited by a small and endangered wolf population. We interviewed 220 people (175 from the general public, 13 hunters, and 32 livestock owners) through a semi-structured survey organized on a 5-point Likert scale. Public and hunter respondents exhibited neutral to positive attitudes, whereas livestock owners expressed negative to neutral attitudes and revealed a Not-In-My-Backyard sentiment. We found that positive attitudes were linked to a greater receptiveness to increased wolf numbers, particularly in areas of irregular wolf presence. Fear was a significant driver of public attitudes, while the presence of wolves influenced livestock owners’views. For both groups, attitudes were also influenced by perceived costs and benefits. Knowledge about wolves did not significantly influence attitudes, with scores being consistently low across groups, and the myth of reintroduction persisting. Thus, management actions should address the concerns and complaints of individuals directly affected by wolves, dispel common fears and myths, and emphasize the ecological and economic benefits of wolf presence in the territory. Media outlets can serve as strategic partners in engaging the neutral population through untargeted interventions. Prioritizing the input of all groups, including conservationists, is essential for establishing common ground and ensuring sustained coexistence.
Co-design Pedagogy for Computational Thinking Education in K-12: A Systematic Literature Review
Authors: Sunday Amos Oyelere , Agbo Friday Joseph , Suhonen Jarkko
Published: August 2024

The recent popularity of computational thinking (CT) and the desire to apply CT in our daily lives have prompted the need for a successful pedagogical technique for learning CT in K-12 education. The application of co-design pedagogical techniques has the potential to improve students’ CT learning through knowledge sharing and the creation of ideas to solve problems and develop an artifact. However, there is a limited understanding of how co-design pedagogical techniques have been explored to foster CT learning, which could hamper the successful use of co-design as a pragmatic teaching approach. This study examined the ways in which co-design pedagogical techniques have been applied in CT education by implementing a systematic literature review (PRISMA protocol) to document the review analysis. A total of 26 articles that met the inclusion criteria for this study were reviewed. Findings in this study revealed that workshops are the most utilized co-design learning setting and, as expected, the collaborative technique is the co-design pedagogical technique most frequently adopted for implementing CT in K-12 education. NetLogo is the most frequently used co-design tool for teaching and learning CT in K-12 education, and an interdependence exists between NetLogo and the Common Online Data Analysis Platform. Co-design also helps teachers develop the ability to use co-design pedagogical techniques to learn, create content, and integrate CT into their various subjects. This study contributes to practical knowledge by unraveling and advocating the use of dialogical, prompting, framing, and game-based techniques as co-design pedagogical techniques for K-12 teachers and also helps teachers identify useful co-design tools for learning CT.
Organizational Practices for the Inclusion of People with Disabilities. A Scoping Review
Authors: van Berkel Rik , Breit Eric
Published: August 2024

Purpose

The purpose of the scoping review presented in this article is to map the state-of-the-art and development of empirical research of organizational practices designed to include people with disabilities. It contributes to debates on demand-side approaches in promoting the labour-market participation of people with disabilities.

Methods

A literature search took place in PsychINFO, Web of Science, Sociological Abstracts and Sociological Index. Articles included empirical studies published between 2000 and 2023.

Results

The search resulted in 10,535 unique articles of which 146 were included in the review. Organizational inclusion practices have received increasing attention in academic journals in a variety of research fields. In terms of content two groups of studies can be distinguished: hiring studies and studies focusing on organizational practices aimed at employees with disabilities. Hiring studies include studies analysing relationships between a large range of factors and actual hiring or intention to hire as well as studies of a more exploratory nature. Studies focusing on employees with disabilities look at outcomes of specific organizational practices; the conditions promoting their implementation; or explore practices in organizations employing people with disabilities.

Discussion

Based on the findings of the review three suggestions for future research are discussed: (i) internationally comparative studies; (ii) specific attention to small and medium sized enterprises in studies of inclusion; (iii) systematic reviews as follow-ups to scoping reviews.
Health-related quality of life is an independent predictor of mortality and hospitalisations in transthyretin amyloid cardiomyopathy: a prospective cohort study
Authors: Poledniczek Michael , Kronberger Christina , Willixhofer Robin , Ermolaev Nikita , Cherouny Bernhard , Dachs Theresa-Marie , Rettl René , Binder-Rodriguez Christina , Camuz Ligios Luciana , Gregshammer Bernhard , Kammerlander Andreas Anselm , Kastner Johannes , Bergler-Klein Jutta , Duca Franz , Badr Eslam Roza
Published: August 2024

Purpose

Transthyretin amyloid cardiomyopathy (ATTR-CM) is associated with severely impaired health-related quality of life (HRQL). HRQL is an independent predictor of outcome in heart failure (HF), but data on patients with ATTR-CM is scarce. This study therefore aims to evaluate the association of HRQL with outcome in ATTR-CM.

Methods

Patients from our prospective ATTR-CM registry were assessed using the Kansas City cardiomyopathy questionnaire (KCCQ), the Minnesota living with HF questionnaire (MLHFQ), and the EuroQol five dimensions questionnaire (EQ-5D). Cox regression analysis was utilised to assess the impact of HRQL on all-cause mortality.

Results

167 patients [80 years; interquartile range (IQR): 76–84; 80.8% male] were followed for a median of 27.6 (IQR: 9.7–41.8) months. The primary endpoint of all-cause mortality was met by 43 (25.7%) patients after a median period of 16.2 (IQR: 9.1–28.1) months. In a univariate Cox regression for mortality, a 10-point change in the KCCQ implied a hazard ratio (HR) of 0.815 [95%-confidence interval (CI): 0.725–0.916; p = 0.001], in the EQ-5D VAS of 0.764 (95%-CI: 0.656–0.889; p < 0.001), and 1.163 (95%-CI: 1.114–1.433; p < 0.001) in the MLHFQ. After adjustment for established biomarkers of HF, all-cause mortality was predicted independently by the EQ-5D VAS (HR: 0.8; 95%-CI: 0.649–0.986; p = 0.037; per 10 points) and the MLHFQ (HR: 1.228; 95%-CI: 1.035–1.458; p = 0.019; per 10 points).

Conclusion

HRQL is a predictor of outcome in ATTR-CM. The EQ-5D VAS and the MLHFQ predict survival independent of biomarkers of HF.
Spaziergang in die Zukunft der Altenpflege: Wie Robis die Lebensqualität von Oldies verbessern könnten
Authors: Ďuranová Lenka , Schrödel Frank , Rösner Marlene
Published: August 2024

In der Altenpflege herrscht Fachkräftemangel. Dieser beeinträchtigt Organisationen, Personal, Pflegebedürftige sowie Angehörige und erfordert innovative Lösungen. In der Berufspraxis entstand eine konkrete Forderung: Roboter, die mit den Älteren spazieren gehen. Dieser gehen wir nach. In diesem Beitrag skizzieren wir die Notwendigkeit einer Technologieinnovation in der Altenpflege aus wirtschaftspsychologischer Sicht, danach potenzielle Vorteile des begleitenden Roboters, seine Anwendungsszenarien, Hindernisse bei der Einführung und die notwendigen Entwicklungsschritte. Schließlich appellieren wir an die Praxis, die Technologieentwicklung zu unterstützen.
Thermo-Structural Coupled Finite Element Analysis of Repair Process for Steam Turbine Blade Using Laser-Directed Energy Deposition Method
Authors: Arai Masayuki , Fujita Seiji , Meng Yuxian , Izumi Taisei
Published: August 2024

This study presents a numerical additive manufacturing simulation aimed at simulating the shape recovery process of a steam turbine blade damaged by corrosion, using laser-directed energy deposition (LDED). The simulation integrates the finite element (FE) method with heat conduction and thermo-elastoplastic constitutive equations, incorporating phase transformation. The additive manufacturing process by LDED was modeled using the death-birth algorithm, wherein a deposition layer is defined as a virtual element. Its stiffness and thermal properties activated when the laser irradiation regions overlapped. In this study, the shape of the virtual element was determined based on the cross-sectional shape of the deposition layer manufactured under various laser conditions. To validate the numerical simulation results, additive manufacturing was conducted for one pass deposition in the width direction at the center of a cantilever-supported plate made of SUS304 steel, and the changes in displacement at the free edges with respect to the process time were compared. The obtained FE results are in good agreement with the experimental results. Finally, an FE simulation was performed for the shape recovery of a steam turbine blade thinned due to corrosion damage. The results revealed that the residual stress component becomes more compressive as the laser output decreases and scanning speed increases, which is advantageous for improving the fatigue strength of steam turbine blades.
Where Does Cardinality Come From?
Authors: Pantsar Markus , Assadian Bahram
Published: August 2024

How do we acquire the notions of cardinality and cardinal number? In the (neo-)Fregean approach, they are derived from the notion of equinumerosity. According to some alternative approaches, defended and developed by Husserl and Parsons among others, the order of explanation is reversed: equinumerosity is explained in terms of cardinality, which, in turn, is explained in terms of our ordinary practices of counting. In their paper, ‘Cardinality, Counting, and Equinumerosity’, Richard Kimberly Heck proposes that instead of equinumerosity or counting, cardinality is derived from a cognitively earlier notion of just as many. In this paper, we assess Heck’s proposal in terms of contemporary theories of number concept acquisition. Focusing on bootstrapping theories, we argue that there is no evidence that the notion of just as many is cognitively primary. Furthermore, since the acquisition of cardinality is an enculturated process, the cognitive primariness of these notions, possibly including just as many, depends on various external cultural factors. Therefore, being possibly a cultural construction, just as many could be one among several notions used in the acquisition of cardinality and cardinal number concepts. This paper thus challenges those accounts which seek for a fundamental concept underlying all aspects of numerical cognition.
Flexible surface acoustic wave technology for enhancing transdermal drug delivery
Authors: Zhang Jikai , Bahar Duygu , Ong Hui Ling , Arnold Peter , Zhang Meng , Jiang Yunhong , Tao Ran , Haworth Luke , Yang Xin , Brain Chelsea , Rahmati Mohammad , Torun Hamdi , Wu Qiang , Luo Jingting , Fu Yong-Qing
Published: August 2024

Transdermal drug delivery provides therapeutic benefits over enteric or injection delivery because its transdermal routes provide more consistent concentrations of drug and avoid issues of drugs affecting kidneys and liver functions. Many technologies have been evaluated to enhance drug delivery through the relatively impervious epidermal layer of the skin. However, precise delivery of large hydrophilic molecules is still a great challenge even though microneedles or other energized (such as electrical, thermal, or ultrasonic) patches have been used, which are often difficult to be integrated into small wearable devices. This study developed a flexible surface acoustic wave (SAW) patch platform to facilitate transdermal delivery of macromolecules with fluorescein isothiocyanates up to 2000 kDa. Two surrogates of human skin were used to evaluate SAW based energized devices, i.e., delivering dextran through agarose gels and across stratum corneum of pig skin into the epidermis. Results showed that the 2000 kDa fluorescent molecules have been delivered up to 1.1 mm in agarose gel, and the fluorescent molecules from 4 to 2000 kDa have been delivered up to 100 µm and 25 µm in porcine skin tissue, respectively. Mechanical agitation, localised streaming, and acousto-thermal effect generated on the skin surface were identified as the main mechanisms for promoting drug transdermal transportation, although micro/nanoscale acoustic cavitation induced by SAWs could also have its contribution. SAW enhanced transdermal drug delivery is dependent on the combined effects of wave frequency and intensity, duration of applied acoustic waves, temperature, and drug molecules molecular weights.

Graphical Abstract

Graphical Abstract: Flexible surface acoustic wave technology for enhancing transdermal drug delivery
Optimization and Kinetic Study of Manganese Leaching from Pyrolusite Ore in Hydrochloric Acid Solutions with Oxalic Acid
Authors: Karacahan Mehmet Kayra
Published: August 2024

The leaching behavior of pyrolusite minerals was examined in hydrochloric acid solutions, including oxalic acid, to evaluate the influence of various experimental conditions. The optimum parameters for the leaching process were found in the first stage, and the process's kinetics were assessed in the second. The concentrations of oxalic acid, hydrochloric acid, and temperature were chosen as independent variables in the optimization experiments, with the central composite design used to analyze the experimental data. The optimum concentrations for oxalic acid, hydrochloric acid, and temperature were determined to be 0.75 mol/L, 1.2 mol/L, and 60 °C, respectively. The leaching rate was determined to be 97.4% for 120 min of response time in optimum situations. The kinetic assessment experiments studied the effects of solid/liquid ratio, particle size, stirring speed, and temperature on the manganese leaching rate from pyrolusite. In the studies, the leaching rate was shown to rise with increasing temperature and stirring speed, as well as with decreasing particle size and solid/liquid ratio. The kinetic analysis revealed that the leaching kinetics matched the mixed kinetic model, and a mathematical model for the leaching process was developed. This process's activation energy was determined to be 29.05 kJ/mol.

Graphical Abstract
Colour-coded decisions: an experiment on case-based decision theory
Authors: Radoc Benjamin
Published: August 2024

Decision makers typically possess limited knowledge on states of the world so that use of information from past similar experiences is reasonable. This analogical thinking is formalised by case-based decision theory (CBDT). We created a novel experimental setting to validate the predictive power of CBDT versus Bayesian reasoning. Participants encountered a salient but irrelevant cue which a Bayesian decision maker is likely to ignore but a case-based decision maker may use in assessing similarity. We find that although the irrelevant similarity cue was used, the pattern in participants’ decisions is neither case-based nor Bayesian. The results suggest that CBDT does not apply in simple decision settings where similarity cues are uninformative.
Macroscopic Traffic Modeling Using Probe Vehicle Data: A Machine Learning Approach
Authors: Jin Ling , Xu Xiaodan , Wang Yuhan , Lazar Alina , Sadabadi Kaveh Farokhi , Spurlock C. Anna , Needell Zachary , Don Duleep Rathgamage , Amirgholy Mahyar , Asudegi Mona
Published: August 2024

The macroscopic fundamental diagram (MFD) captures an orderly relationship among traffic flow, density, and speed at the network level. It is a simple yet powerful tool for modeling traffic dynamics in large urban networks with broad application in traffic control and management. However, empirically derived MFDs in urban regions require high-resolution traffic data from the network. Having the network flow and vehicular density estimated at the (granular) census tract level using vehicle probe data, we apply machine learning methods to predict the MFDs across U.S. urban areas and capture the impacts of location-specific input features on the network flow–density relationships at a large scale. The results show that, among the four tested machine learning approaches (Random Forest, XGBoost, Support Vector Machine, and Neural Network), XGBoost delivers the best performance in predicting network traffic flow based on vehicular density and location attributes. Using interaction Shapley Additive explanation (SHAP) values and partial correlation analysis, we examine the factors influencing MFD shapes across different locations. Our empirical findings reveal that across U.S. urban areas, network topology, transportation infrastructure, and land use are primary factors shaping MFD curves, while demand and trip-related factors play a lesser role. Specifically, higher ranking roads, centrality, and development levels correlate positively with network capacity and critical density, whereas negative associations are observed for network connectivity, mixed-use development, and road roughness levels.
Advances in metal–organic frameworks as adsorbents, photocatalysts and membranes: a new frontier in water purification
Authors: Kiteto Moses , Vidija Beryl , Mecha Cleophas Achisa , Mrosso Register , Chollom Martha N.
Published: August 2024

Water is an essential and irreplaceable necessity for life on earth, sustaining ecosystems, nourishing agriculture and vital for human survival. However, increasing population and industrialization has exacerbated water scarcity and pollution. The Sustainable Development Goal 6 focuses on clean water and sanitation for all; thus, water purification and conservation are key priorities globally. Rampant pollution of water sources by emerging bio-recalcitrant contaminants, often deviant of conventional treatment methods, necessitates new approaches to water treatment. In this regard, metal organic frameworks (MOFs) are gaining prominence and offer solutions in versatile applications due to their unique structural characteristics and tunable properties. This review provides a comprehensive analysis of MOFs, covering their diverse structures, types, synthesis methods and characterization techniques. We explore the application of MOFs in water purification, as adsorbents, photocatalysts, and in membrane separation. The mechanism of operation of MOFs in each application is critically evaluated. The effect of the water treatment methods on energy consumption has also been investigated. We propose that for MOFs application in water treatment to be competitive and sustainable, there is need to address key issues such as synthesis of highly selective MOFs, recovery and reuse, scalability (pilot and industrial scale), and integration with existing water treatment technologies to create synergy. We provide future perspectives on these aspects.
Geo-Political Rivalry and Anti-Immigrant Sentiment: A Conjoint Experiment in 22 Countries
Authors: WIMMER ANDREAS , BONIKOWSKI BART , CRABTREE CHARLES , FU ZHENG , GOLDER MATT , TSUTSUI KIYOTERU
Published: August 2024

Introducing an international relations perspective into the literature on anti-immigrant attitudes, we hypothesize that immigrants from rival countries will be shunned and immigrants from allied countries preferred, especially by respondents who identify more strongly with the nation. We fielded a forced-choice conjoint experiment in 22 countries, whereby respondents chose between applicants for permanent resident status with randomized attributes. We identified rival and allied countries of origin for each surveyed country, with one such pair sharing a similar racial and cultural make-up as the majority of respondents, and one pair being more dissimilar. We find that discrimination against immigrants from rival states is so pronounced that it results in a net preference for racially and culturally dissimilar immigrants. Since we fielded the surveys amidst the Russian invasion of Ukraine, we are able to leverage exogenous changes in the intensity of one rivalry, providing further evidence for the proposed mechanism.
40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice
Authors: Sun Xiaoting , Dias Liliana , Peng Chenlei , Zhang Ziyi , Ge Haoting , Wang Zejun , Jin Jiayi , Jia Manli , Xu Tao , Guo Wei , Zheng Wu , He Yan , Wu Youru , Cai Xiaohong , Agostinho Paula , Qu Jia , Cunha Rodrigo A. , Zhou Xuzhao , Bai Ruiliang , Chen Jiang-fan
Published: August 2024

The glymphatic-lymphatic system is increasingly recognized as fundamental for the homeostasis of the brain milieu since it defines cerebral spinal fluid flow in the brain parenchyma and eliminates metabolic waste. Animal and human studies have uncovered several important physiological factors regulating the glymphatic system including sleep, aquaporin-4, and hemodynamic factors. Yet, our understanding of the modulation of the glymphatic system is limited, which has hindered the development of glymphatic-based treatment for aging and neurodegenerative disorders. Here, we present the evidence from fluorescence tracing, two-photon recording, and dynamic contrast-enhanced magnetic resonance imaging analyses that 40 Hz light flickering enhanced glymphatic influx and efflux independently of anesthesia and sleep, an effect attributed to increased astrocytic aquaporin-4 polarization and enhanced vasomotion. Adenosine-A2A receptor (A2AR) signaling emerged as the neurochemical underpinning of 40 Hz flickering-induced enhancement of glymphatic flow, based on increased cerebrofluid adenosine levels, the abolishment of enhanced glymphatic flow by pharmacological or genetic inactivation of equilibrative nucleotide transporters-2 or of A2AR, and by the physical and functional A2AR–aquaporin-4 interaction in astrocytes. These findings establish 40 Hz light flickering as a novel non-invasive strategy of enhanced glymphatic flow, with translational potential to relieve brain disorders.
Dental behaviour support: can we improve qualitative research on patient experience?
Authors: Holmes Richard D.
Published: August 2024

Data sources

Databases included Embase, Medline (via OVID) and PsycINFO (via EBSCO). Studies referenced within included review articles were additionally screened for relevance.

Study selection

This review focused upon qualitative research studies and their use of dental behaviour support (DBS) tools to support dental care. Included studies were restricted to those in English and published since 1997. Screening of studies involved several authors according to pre-agreed inclusion and exclusion criteria. In the event of disagreement, a third author mediated the collaborative discussion.

Data extraction and synthesis

Included studies first provided baseline study information including the type of qualitative research, the population studied and details of the type(s) of DBS under investigation. Then the qualitative data generated by each study, together with any interpretation provided by the authors, was entered onto bespoke data collection forms. A thematic synthesis approach was adopted. The authors generated new themes supported by selected quotations. The methodological quality of each included study was explored through a recognised tool and the level of confidence provided by each study was informed by the GRADE-CERQual assessment process.

Results

Twenty-three studies were included. Most studies used semi-structured interviews, followed by focus groups and a small number of video diaries. For most studies, the focus was upon the dental care of children with a good proportion of these exploring dental general anaesthesia (DGA). Indeed, DGA was the most studied DBS technique. Whilst some studies explored adults’ experiences of DBS, none of the included studies centred upon medically compromised or older adults. The review authors identified five themes following data synthesis. These themes included the following areas (abridged and modified from the review paper): trust; information sharing; control and autonomy; perceived treatment success and failure of DBS techniques; and the longer-term impact of DBS techniques upon patients.

Conclusions

Qualitative research has more to offer our understanding of DBS techniques and the impact they have upon patient care experience. There is a need for research to explore a wider range of DBS techniques used in isolation or in combination. Patient reported experiences of care should be considered in the development of outcome measures and any related DBS Core Outcome Set.
Diagnostic utility of DNA methylation analysis in genetically unsolved pediatric epilepsies and CHD2 episignature refinement
Authors: LaFlamme Christy W. , Rastin Cassandra , Sengupta Soham , Pennington Helen E. , Russ-Hall Sophie J. , Schneider Amy L. , Bonkowski Emily S. , Almanza Fuerte Edith P. , Allan Talia J. , Zalusky Miranda Perez-Galey , Goffena Joy , Gibson Sophia B. , Nyaga Denis M. , Lieffering Nico , Hebbar Malavika , Walker Emily V. , Darnell Daniel , Olsen Scott R. , Kolekar Pandurang , Djekidel Mohamed Nadhir , Rosikiewicz Wojciech , McConkey Haley , Kerkhof Jennifer , Levy Michael A. , Relator Raissa , Lev Dorit , Lerman-Sagie Tally , Park Kristen L. , Alders Marielle , Cappuccio Gerarda , Chatron Nicolas , Demain Leigh , Genevieve David , Lesca Gaetan , Roscioli Tony , Sanlaville Damien , Tedder Matthew L. , Gupta Sachin , Jones Elizabeth A. , Weisz-Hubshman Monika , Ketkar Shamika , Dai Hongzheng , Worley Kim C. , Rosenfeld Jill A. , Chao Hsiao-Tuan ,   Undiagnosed Diseases Network, Neale Geoffrey , Carvill Gemma L. ,   University of Washington Center for Rare Disease Research, Wang Zhaoming , Berkovic Samuel F. , Sadleir Lynette G. , Miller Danny E. , Scheffer Ingrid E. , Sadikovic Bekim , Mefford Heather C.
Published: August 2024

Sequence-based genetic testing identifies causative variants in ~ 50% of individuals with developmental and epileptic encephalopathies (DEEs). Aberrant changes in DNA methylation are implicated in various neurodevelopmental disorders but remain unstudied in DEEs. We interrogate the diagnostic utility of genome-wide DNA methylation array analysis on peripheral blood samples from 582 individuals with genetically unsolved DEEs. We identify rare differentially methylated regions (DMRs) and explanatory episignatures to uncover causative and candidate genetic etiologies in 12 individuals. Using long-read sequencing, we identify DNA variants underlying rare DMRs, including one balanced translocation, three CG-rich repeat expansions, and four copy number variants. We also identify pathogenic variants associated with episignatures. Finally, we refine the CHD2 episignature using an 850 K methylation array and bisulfite sequencing to investigate potential insights into CHD2 pathophysiology. Our study demonstrates the diagnostic yield of genome-wide DNA methylation analysis to identify causal and candidate variants as 2% (12/582) for unsolved DEE cases.
The unusual structural properties and potential biological relevance of switchback DNA
Authors: Madhanagopal Bharath Raj , Talbot Hannah , Rodriguez Arlin , Louis Jiss Maria , Zeghal Hana , Vangaveti Sweta , Reddy Kaalak , Chandrasekaran Arun Richard
Published: August 2024

Synthetic DNA motifs form the basis of nucleic acid nanotechnology. The biochemical and biophysical properties of these motifs determine their applications. Here, we present a detailed characterization of switchback DNA, a globally left-handed structure composed of two parallel DNA strands. Compared to a conventional duplex, switchback DNA shows lower thermodynamic stability and requires higher magnesium concentration for assembly but exhibits enhanced biostability against some nucleases. Strand competition and strand displacement experiments show that component sequences have an absolute preference for duplex complements instead of their switchback partners. Further, we hypothesize a potential role for switchback DNA as an alternate structure in sequences containing short tandem repeats. Together with small molecule binding experiments and cell studies, our results open new avenues for switchback DNA in biology and nanotechnology.
Allosteric inhibition of CFTR gating by CFTRinh-172 binding in the pore
Authors: Gao Xiaolong , Yeh Han-I , Yang Zhengrong , Fan Chen , Jiang Fan , Howard Rebecca J. , Lindahl Erik , Kappes John C. , Hwang Tzyh-Chang
Published: August 2024

Loss-of-function mutations of the CFTR gene cause the life-shortening genetic disease cystic fibrosis (CF), whereas overactivity of CFTR may lead to secretory diarrhea and polycystic kidney disease. While effective drugs targeting the CFTR protein have been developed for the treatment of CF, little progress has been made for diseases caused by hyper-activated CFTR. Here, we solve the cryo-EM structure of CFTR in complex with CFTRinh-172 (Inh-172), a CFTR gating inhibitor with promising potency and efficacy. We find that Inh-172 binds inside the pore of CFTR, interacting with amino acid residues from transmembrane segments (TMs) 1, 6, 8, 9, and 12 through mostly hydrophobic interactions and a salt bridge. Substitution of these residues lowers the apparent affinity of Inh-172. The inhibitor-bound structure reveals re-orientations of the extracellular segment of TMs 1, 8, and 12, supporting an allosteric modulation mechanism involving post-binding conformational changes. This allosteric inhibitory mechanism readily explains our observations that pig CFTR, which preserves all the amino acid residues involved in Inh-172 binding, exhibits a much-reduced sensitivity to Inh-172 and that the apparent affinity of Inh-172 is altered by the CF drug ivacaftor (i.e., VX-770) which enhances CFTR’s activity through binding to a site also comprising TM8.
Orexin neurons mediate temptation-resistant voluntary exercise
Authors: Tesmer Alexander L. , Li Xinyang , Bracey Eva , Schmandt Cyra , Polania Rafael , Peleg-Raibstein Daria , Burdakov Denis
Published: August 2024

Despite the well-known health benefits of physical activity, many people underexercise; what drives the prioritization of exercise over alternative options is unclear. We developed a task that enabled us to study how mice freely and rapidly alternate between wheel running and other voluntary activities, such as eating palatable food. When multiple alternatives were available, mice chose to spend a substantial amount of time wheel running without any extrinsic reward and maintained this behavior even when palatable food was added as an option. Causal manipulations and correlative analyses of appetitive and consummatory processes revealed this preference for wheel running to be instantiated by hypothalamic hypocretin/orexin neurons (HONs). The effect of HON manipulations on wheel running and eating was strongly context-dependent, being the largest in the scenario where both options were available. Overall, these data suggest that HON activity enables an eat–run arbitration that results in choosing exercise over food.
A Reinforcement Learning approach to study climbing plant behaviour
Authors: Nasti Lucia , Vecchiato Giacomo , Heuret Patrick , Rowe Nicholas P. , Palladino Michele , Marcati Pierangelo
Published: August 2024

A plant’s structure is the result of constant adaptation and evolution to the surrounding environment. From this perspective, our goal is to investigate the mass and radius distribution of a particular plant organ, namely the searcher shoot, by providing a Reinforcement Learning (RL) environment, that we call Searcher-Shoot, which considers the mechanics due to the mass of the shoot and leaves. We uphold the hypothesis that plants maximize their length, avoiding a maximal stress threshold. To do this, we explore whether the mass distribution along the stem is efficient, formulating a Markov Decision Process. By exploiting this strategy, we are able to mimic and thus study the plant’s behavior, finding that shoots decrease their diameters smoothly, resulting in an efficient distribution of the mass. The strong accordance between our results and the experimental data allows us to remark on the strength of our approach in the analysis of biological systems traits.
Variation of temperature increase rate in the Northern Hemisphere according to latitude, longitude and altitude: the Turkey example
Authors: Şevgin Fatih , Öztürk Ali
Published: August 2024

Global climate change notably influences meteorological variables such as temperature, affecting regions and countries worldwide. In this study, monthly average temperature data spanning 73 years (1950–2022) were analyzed for 28 stations in the city centers across seven regions of Turkey. The station warming rates (SWR) were calculated for selected stations and the overall country using Singular Spectrum Analysis (SSA) and Least Square Polynomial Fit (LSPF) methods. The temperature trend in Turkey exhibited a decline until the late 1970s, followed by a continuous rise due to global warming. Between 1980 and 2022, the average SWR in Turkey was found to be 0.52 °C/decade. The SWR was determined to be the lowest in Antakya (0.28 °C/decade) and the highest in Erzincan (0.69 °C/decade). The relationship between SWR and latitude, longitude, altitude, and distance to Null Island (D2NI) was explored through linear regression analysis. Altitude and D2NI were found to be the most significant variables, influencing the SWR. For altitude, the correlation coefficient (R) was 0.39 with a statistically significant value (p) of 0.039. For D2NI, R, and p values were 0.39 and 0.038, respectively. Furthermore, in the multiple regression analysis involving altitude and D2NI, R and p values were determined to be 0.50 and 0.029, respectively. Furthermore, the collinearity analysis indicates no collinearity between altitude and D2NI, suggesting that their effects are separated in the multiple regression.
Evaluation of filler activation for sustainable FRP composite by studying properties, mechanism, and stability
Authors: Naguib Hamdy M.
Published: August 2024

The aim is to develop new fiber-reinforced polymer (FRP) water pipe by activating fiber glass (FG) by vinyltriethoxysilane (VS) getting vinylsilane-activated FG (AFG) for filling vinylester (VE) via continuous winding to make a novel VE-AFG composite. The novelty of this work is the activation of fiber glass by vinylsilane as a single filler in vinylester and compounding them via a two-dimensional continuous winding process for the first time. The crosslinking occurred in the AFG/VE/curing agent system after activation. The activated composites increased thermal stability; 25% VE-AGF increased the degradation temperatures at 10%, 25%, and 50% weight loss by 73.3%, 10%, and 7.2%. With the activated 20% composite, values of axial strength, hoop strength, and hardness were developed by 6.3%, 2%, and 8.7%, respectively. The decay resistance to different microorganisms was increased with VE-AFG composites as a result of a sharp decrease in biodegradability percentages. The activated composites are stable toward water absorption; the least percentage was recorded by 25% VE-AFG, which minimized the water absorptivity by more than 62%. The reported characterization sentence approves enhancement of thermal, physical, and mechanical stability of sustainable vinylester-fiber glass composites manufactured by continuous winding; this is recommended for application in water pipe systems.
Clinical relevance of critical plasma homocysteine levels in predicting rupture risk for small and medium-sized intracranial aneurysms
Authors: Lu Wang , Shiwei Yan , Aimin Li , Kang Xie
Published: August 2024

Plasma homocysteine (Hcy) has been globally recognized as an independent risk factor for various neurovascular diseases. In this study, the authors investigated the relationship between critical Hcy concentration and the risk of rupture in intracranial aneurysms (IAs). This study collected data from 423 patients with both ruptured and unruptured IAs. We compared demographic data, vascular rupture risk factors, and laboratory test results between the two groups. Multivariable logistic regression analysis was employed to determine the correlation between critical plasma Hcy levels and the risk of rupture in small to medium-sized IAs. A total of 330 cases of ruptured intracranial aneurysms (RIA) and 93 cases of unruptured intracranial aneurysms (UIA) were included. Univariate analysis revealed statistically significant differences between the ruptured and unruptured groups in terms of hypertension, hyperlipidemia, plasma Hcy levels, and IA morphology (all P < 0.05). Multivariable logistic regression analysis indicated that hypertension (odds ratio [OR] 0.504; 95% confidence interval [CI] 0.279–0.911; P = 0.023), hyperlipidemia (OR 1.924; 95% CI 1.079–3.429; P = 0.027), and plasma Hcy levels (OR 1.420; 95% CI 1.277–1.578; P < 0.001) were independently associated with the rupture of small to medium-sized IAs, all with statistical significance (P < 0.05). Our study suggests that critical plasma Hcy levels are an independent risk factor for increased rupture risk in small to medium-sized intracranial aneurysms. Therefore, reducing plasma Hcy levels may be considered a valuable strategy to mitigate the risk of intracranial vascular abnormalities rupture and improve patient prognosis.
Synthesis and preclinical testing of a selective beta-subtype agonist of thyroid hormone receptor ZTA-261
Authors: Nambo Masakazu , Nishiwaki-Ohkawa Taeko , Ito Akihiro , Ariki Zachary T. , Ito Yuka , Kato Yuuki , Yar Muhammad , Yim Jacky C. -H. , Kim Emily , Sharkey Elizabeth , Kano Keiko , Mishiro-Sato Emi , Okimura Kosuke , Maruyama Michiyo , Ota Wataru , Furukawa Yuko , Nakayama Tomoya , Kobayashi Misato , Horio Fumihiko , Sato Ayato , Crudden Cathleen M. , Yoshimura Takashi
Published: August 2024

Background

Thyroid hormones (TH) regulate the basal metabolic rate through their receptors THRα and THRβ. TH activates lipid metabolism via THRβ, however, an excess amount of TH can lead to tachycardia, bone loss, and muscle wasting through THRα. In recent years, TH analogs that selectively bind to THRβ have gained attention as new agents for treating dyslipidemia and obesity, which continue to pose major challenges to public health worldwide.

Methods

We developed a TH analog, ZTA-261, by modifying the existing THRβ-selective agonists GC-1 and GC-24. To determine the THRβ-selectivity of ZTA-261, an in vitro radiolabeled TH displacement assay was conducted. ZTA-261 was intraperitoneally injected into a mouse model of high-fat diet-induced obesity, and its effectiveness in reducing body weight and visceral fat, and improving lipid metabolism was assessed. In addition, its toxicity in the liver, heart, and bone was evaluated.

Results

ZTA-261 is more selective towards THRβ than GC-1. Although ZTA-261 is less effective in reducing body weight and visceral fat than GC-1, it is as effective as GC-1 in reducing the levels of serum and liver lipids. These effects are mediated by the same pathway as that of T3, a natural TH, as evidenced by similar changes in the expression of TH-induced and lipid metabolism-related genes. The bone, cardiac, and hepatotoxicity of ZTA-261 are significantly lower than those of GC-1.

Conclusions

ZTA-261, a highly selective and less toxic THRβ agonist, has the potential to be used as a drug for treating diseases related to lipid metabolism.
Dye-doped cellulose nanocrystals as novel dusting powders for visualizing latent fingerprints
Authors: Yao Xu , Li Guo-Rui , Wang Jiu-Jiang , Tang Cheng , Li Da-Wu , You Nan , Mao Wei , Li Zhan-Chao , Zhang Si-Qi
Published: August 2024

Green fluorescent curcumin-doped cellulose nanocrystals obtained by anchoring curcumin on cellulose nanocrystals exhibit better performances for detecting high-level features of ridges of fresh and non-fresh latent fingerprints on various substrates.
Photocatalytic functionalization of white phosphorus with aryl bromides and chlorides
Authors: Gawron Martin , Rückel Jannes , Wolf Robert
Published: August 2024

The photocatalytic functionalization of white phosphorus (P4) is achieved with cheap and abundant aryl bromides and chlorides, thus overcoming a significant obstacle in the chemistry of this important feedstock molecule.
Divergent synthesis of δ-valerolactones and furanones via palladium or copper-catalyzed α-hydroxycyclopropanol ring opening cyclizations
Authors: de Andrade Horn Pedro , Collins Michael J. E. , Gudeman Cyrus C. , Fresh Alexandra A. , Dai Mingji
Published: August 2024

Divergent approaches were developed to synthesize δ-valerolactones or furanones via a palladium or copper-catalyzed α-hydroxycyclopropanol ring opening cyclizations, respectively.
Quantum and statistical state-to-state studies of cold Ar + H2+ collisions
Authors: Konings Maarten , González-Lezana Tomás , Camps Simen , Loreau Jérôme
Published: August 2024

We present new state-to-state scattering cross sections and initial-state selected rate coefficients for the 36Ar (1S) + H2+ (X2Σg+,v = 0,j) reactive system for collision energies up to 0.1 eV.
Insights from Li and Zn systems for advancing Mg and Ca metal batteries
Authors: Kim Jinyoung , Kim Minkwan , Lee Jimin , An Jiwoo , Yang Seonmo , Ahn Hyo Chul , Yoo Dong-Joo , Choi Jang Wook
Published: August 2024

This review presents the progress and future direction of Mg and Ca metal batteries with a focus on electrolyte and solid–electrolyte–interphase engineering, by drawing lessons from the more extensively researched Li and Zn metal batteries.
Cation distribution: a descriptor for hydrogen evolution electrocatalysis on transition-metal spinels
Authors: Gomaa Aya K. , Zonkol Maram G. , Khedr Ghada E. , Allam Nageh K.
Published: August 2024

The distribution of cations in spinel structures significantly influences their hydrogen evolution reaction (HER) catalytic activity, as it affects the material's electronic properties, stability, and surface characteristics.
Beyond theory-driven discovery: introducing hot random search and datum-derived structures
Authors: Pickard Chris J.
Published: August 2024

Ephemeral Data-Derived Potential (EDDP)-driven long high-temperature anneals combined with AIRSS, termed as hot-AIRSS, enable the exploration of low-energy configurations of complex materials.
Increasing the diversity of nylonases for poly(ester amide) degradation
Authors: de Witt Jan , Ostheller Maike-Elisa , Jensen Kenneth , van Slagmaat Christian A. M. R. , Polen Tino , Seide Gunnar , Thies Stephan , Wynands Benedikt , Wierckx Nick
Published: August 2024

This study extents the sequence space of 6-aminohexanoate endohydrolases (NylC) for future enzyme engineering strategies to boost their nylonase activities, while in parallel novel polymers were designed to align biodegradability and performance.
Continuous production of 1,2-pentanediol from furfuryl alcohol over highly stable bimetallic Ni–Sn alloy catalysts
Authors: Nimbalkar Ajaysing S. , Oh Kyung-Ryul , Hong Do-Young , Park Byung Gyu , Lee Maeum , Hwang Dong Won , Awad Ali , Upare Pravin P. , Han Seung Ju , Hwang Young Kyu
Published: August 2024

A bimetallic NiSn/ZnO catalyst converts biomass-derived furfuryl alcohol into 1,2-PDO continuously, yielding 91.0% over 400 hours.
Enhancing multi-type coal quality prediction accuracy with fusion spectra and classification models using NIRS and XRF techniques
Authors: Zhang Zhedong , Li Jiaxuan , Gao Rui , Zhao Yang , Zhang Yan , Zhang Lei , Ye Zefu , Zhu Zhujun , Zhang Peihua , Yin Wangbao , Jia Suotang
Published: August 2024

The various analytical indices of coal are important criteria for evaluating the quality of commercial coal.
Three-dimensional inertial focusing based impedance cytometer enabling high-accuracy characterization of electrical properties of tumor cells
Authors: Ni Chen , Yang Mingqi , Yang Shuai , Zhu Zhixian , Chen Yao , Jiang Lin , Xiang Nan
Published: August 2024

A microfluidic impedance cytometer based on 3D inertial focusing acquires high SNR and low CV impedance signals for the high-accuracy electrical characterization and identification of tumor cells.
Eco-friendly, sustainable, and safe energy storage: a nature-inspired materials paradigm shift
Authors: Bertaglia Thiago , Costa Carlos M. , Lanceros-Méndez Senentxu , Crespilho Frank N.
Published: August 2024

This work demonstrates how nature-inspired and derived approaches can significantly impact energy storage. Also, it provides a workflow to accelerate the development of these technologies, helping these batteries move closer to market readiness.
A step towards a green and sustainable method to understand the effect of glucose on a silica filled natural rubber composite
Authors: Bera Abhijit , Yamano Masaki , Kawahara Seiichi , Chattopadhyay Santanu
Published: August 2024

In the present scenario, the world is concerned about producing more environmentally friendly and sustainable products by reducing the carbon footprint, especially in elastomer products.