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Abstract CNS tumours encompass a diverse group of neoplasms with significant morbidity and mortality. The SHH signalling pathway plays a critical role in the pathogenesis of several CNS tumours, including gliomas, medulloblastomas and others. By influencing cellular proliferation, differentiation and migration in CNS tumours, the SHH pathway has emerged as a promising target for therapeutic intervention. Current strategies such as vismodegib and sonidegib have shown efficacy in targeting SHH pathway activation. However, challenges such as resistance mechanisms and paradoxical effects observed in clinical settings underscore the complexity of effectively targeting this pathway. Advances in gene editing technologies, particularly CRISPR/Cas9, have provided valuable tools for studying SHH pathway biology, validating therapeutic targets and exploring novel treatment modalities. These innovations have paved the way for a better understanding of pathway dynamics and the development of more precise therapeutic interventions. In addition, the identification and validation of biomarkers of SHH pathway activation are critical to guide clinical decision making and improve patient outcomes. Molecular profiling and biomarker discovery efforts are critical steps towards personalised medicine approaches in the treatment of SHH pathway-associated CNS tumours. While significant progress has been made in understanding the role of the SHH pathway in CNS tumorigenesis, ongoing research is essential to overcome current therapeutic challenges and refine treatment strategies. The integration of molecular insights with advanced technologies and clinical expertise holds great promise for developing more effective and personalised therapies for patients with SHH pathway-driven CNS tumours. Graphical Abstract

Abstract Whole-exome sequencing (WES), a ground-breaking technology, has emerged as a linchpin in neurology and neurosurgery, offering a comprehensive elucidation of the genetic landscape of various neurological disorders. This transformative methodology concentrates on the exonic portions of DNA, which constitute approximately 1% of the human genome, thus facilitating an expedited and efficient sequencing process. WES has been instrumental in advancing our understanding of neurodegenerative diseases, neuro-oncology, cerebrovascular disorders, and epilepsy by revealing rare variants and novel mutations and providing intricate insights into their genetic complexities. This has been achieved while maintaining a substantial diagnostic yield, thereby offering novel perspectives on the pathophysiology and personalized management of these conditions. The utilization of WES boasts several advantages over alternative genetic sequencing methodologies, including cost-effectiveness, reduced incidental findings, simplified analysis and interpretation process, and reduced computational demands. However, despite its benefits, there are challenges, such as the interpretation of variants of unknown significance, cost considerations, and limited accessibility in resource-constrained settings. Additionally, ethical, legal, and social concerns are raised, particularly in the context of incidental findings and patient consent. As we look to the future, the integration of WES with other omics-based approaches could help revolutionize the field of personalized medicine through its implications in predictive models and the development of targeted therapeutic strategies, marking a significant stride toward more effective and clinically oriented solutions. Graphical Abstract

ABSTRACT: Objectives: This study was performed to investigate the activity of the novel ß-lactam/ß-lactamase inhibitor combination cefepime/enmetazobactam, against recently circulating Enterobacterales isolates from Europe from 2019 to 2021. Methods: A total of 2627 isolates were collected, and antimicrobial susceptibility was determined according to the European Committee on Antimicrobial Susceptibility Testing guidelines. Isolates with phenotypic resistance to ceftriaxone and ceftazidime (but susceptible to meropenem) and isolates nonsusceptible to meropenem were screened for the presence of ß-lactamases. Results: Overall, susceptibility to third-generation cephalosporins was 77%, and 97.3% were susceptible to meropenem. Cefepime/enmetazobactam susceptibility was 97.9% (72% of these isolates were Klebsiella pneumoniae from Italy), compared with 80.0% susceptibility to piperacillin/tazobactam and 99.4% to ceftazidime/avibactam. A total of 320 isolates (12.2%) were resistant to third-generation cephalosporins but susceptible to meropenem, and virtually all (96.3%) carried an extended-spectrum ß-lactamase with or without an AmpC and these were all susceptible to cefepime/enmetazobactam. Most meropenem-nonsusceptible isolates carried a KPC (68%), which were not inhibited by cefepime/enmetazobactam but were inhibited by ceftazidime/avibactam. Additionally, most meropenem-nonsusceptible isolates carrying OXA-48 (9/12 isolates) were susceptible to cefepime/enmetazobactam. Conclusions: Cefepime/enmetazobactam was highly active against Enterobacterales isolates, especially those resistant to third-generation cephalosporins. These data suggest that cefepime/enmetazobactam could be used as a carbapenem-sparing agent to replace piperacillin/tazobactam.

Abstract Background Malaria community case management (CCM) can improve timely access to healthcare, and CCM programmes in sub-Saharan Africa are expanding from serving children under 5 years (CU5) only to all ages. This report characterizes malaria case management in the setting of an age-expanded CCM programme in Chadiza District, Zambia. Methods Thirty-three households in each of 73 eligible communities were randomly selected to participate in a household survey preceding a trial of proactive CCM (NCT04839900). All household members were asked about fever in the prior two weeks and received a malaria rapid diagnostic test (RDT); those reporting fever were asked about healthcare received. Weighted population estimates were calculated and mixed effects regression was used to assess factors associated with malaria care seeking. Results Among 11,030 (98.6%) participants with RDT results (2,357 households), parasite prevalence was 19.1% by RDT; school-aged children (SAC, 5–14 years) had the highest prevalence (28.8%). Prior fever was reported by 12.4% of CU5, 7.5% of SAC, and 7.2% of individuals ≥ 15 years. Among those with prior fever, 34.0% of CU5, 56.0% of SAC, and 22.6% of individuals ≥ 15 years had a positive survey RDT and 73.7% of CU5, 66.5% of SAC, and 56.3% of individuals ≥ 15 years reported seeking treatment; 76.7% across all ages visited a CHW as part of care. Nearly 90% (87.8%) of people who visited a CHW reported a blood test compared with 73.5% seen only at a health facility and/or pharmacy (p

Abstract Background Oesophageal cancer surgery represents a high perioperative risk of complications to patients, such as postoperative pulmonary complications (PPCs). Postoperative analgesia may influence these risks, but the most favourable analgesic technique is debated. This review aims to provide an updated evaluation of whether thoracic epidural analgesia (TEA) has benefits compared to other analgesic techniques in patients undergoing oesophagectomy surgery. Our hypothesis is that TEA reduces pain scores and PPCs compared to intravenous opioid analgesia in patients post-oesophagectomy. Methods Electronic databases PubMed, Excerpta Medica Database (EMBASE) and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomised trials of analgesic interventions in patients undergoing oesophagectomy surgery. Only trials including thoracic epidural analgesia compared with other analgesic techniques were included. The primary outcome was a composite of respiratory infection, atelectasis and respiratory failure (PPCs), with pain scores at rest and on movement as secondary outcomes. Data was pooled using random effect models and reported as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CIs). Results Data from a total of 741 patients in 10 randomised controlled trials (RCTs) from 1993 to 2023 were included. Nine trials were open surgery, and one trial was laparoscopic. Relative to intravenous opioids, TEA significantly reduced a composite of PPCs (risk ratio (RR) 3.88; 95% confidence interval (CI) 1.98–7.61; n = 222; 3 RCTs) and pain scores (0–100-mm visual analogue scale or VAS) at rest at 24 h (MD 9.02; 95% CI 5.88–12.17; n = 685; 10 RCTs) and 48 h (MD 8.64; 95% CI 5.91–11.37; n = 685; 10 RCTs) and pain scores on movement at 24 h (MD 14.96; 95% CI 5.46–24.46; n = 275; 4 RCTs) and 48 h (MD 16.60; 95% CI 8.72–24.47; n = 275; 4 RCTs). Conclusions Recent trials of analgesic technique in oesophagectomy surgery are restricted by small sample size and variation of outcome measurement. Despite these limitations, current evidence indicates that thoracic epidural analgesia reduces the risk of PPCs and severe pain, compared to intravenous opioids in patients following oesophageal cancer surgery. Future research should include minimally invasive surgery, non-epidural regional techniques and record morbidity, using core outcome measures with standardised endpoints. Trial registration Prospectively registered on PROSPERO (CRD42023484720).

Abstract Background The protective effectiveness of vector control in malaria relies on how the implemented tools overlap with mosquito species-specific compositions and bionomic traits. In Ethiopia, targeted entomological data enabling strategic decision-making are lacking around high-risk migrant worker camps in the lowlands and resident communities in the highlands—resulting in suboptimal malaria control strategies for both populations. This study investigates spatial and temporal mosquito behavior, generating baseline evidence that will improve malaria control for both migrant workers in the lowlands and their home communities in the highlands. Methods Hourly Centers for Disease Control and Prevention (CDC) light trap collections were performed indoors and outdoors during the peak (October to December 2022) and minor (March to May 2023) malaria transmission seasons. These seasons coincide with the post-long rain and post-short rain seasons, respectively. Eight resident households were sampled from each of four villages in the highlands and eight households/farm structures on and near farms in four villages in the lowlands. The sampling occurred between 18:00 and 06:00. Spatiotemporal vector behaviors and hourly indoor and outdoor mosquito capture rates, used as a proxy for human biting rates, were calculated for overall catches and for individual species. Adult mosquitoes were identified using morphological keys, and a subset of samples were confirmed to species by sequencing ribosomal DNA internal transcribed spacer region 2 (ITS2) and/or mitochondrial DNA cytochrome c oxidase subunit 1 (Cox1). Results In the highlands, 4697 Anopheles mosquitoes belonging to 13 morphologically identified species were collected. The predominant species of Anopheles identified in the highlands was An. gambiae sensu lato (s.l.) (n = 1970, 41.9%), followed by An. demeilloni (n = 1133, 24.1%) and An. cinereus (n = 520, 11.0%). In the lowland villages, 3220 mosquitoes belonging to 18 morphological species were collected. Anopheles gambiae s.l. (n = 1190, 36.9%), An. pretoriensis (n = 899, 27.9%), and An. demeilloni (n = 564, 17.5%) were the predominant species. A total of 20 species were identified molecularly, of which three could not be identified to species through comparison with published sequences. In highland villages, the indoor Anopheles mosquito capture rate was much greater than the outdoor rate. This trend reversed in the lowlands, where the rate of outdoor captures was greater than the indoor rate. In both highlands and lowlands, Anopheles mosquitoes showed early biting activities in the evening, which peaked between 18:00 and 21:00, for both indoor and outdoor locations. Conclusions The high diversity of Anopheles vectors and their variable behaviors result in a dynamic and resilient transmission system impacting both exposure to infectious bites and intervention effectiveness. This creates gaps in protection allowing malaria transmission to persist. To achieve optimal control, one-size-fits-all strategies must be abandoned, and interventions should be tailored to the diverse spatiotemporal behaviors of different mosquito populations. Graphical Abstract

Biodegradable polymeric coatings are being explored as a preventive strategy for orthopaedic device-related infection. In this study, titanium surfaces (Ti) were coated with poly-D,L-lactide (PDLLA, (P)), polyethylene-glycol poly-D,L-lactide (PEGylated-PDLLA, (PP20)), or multi-layered PEGylated-PDLLA (M), with or without 1 % silver sulfadiazine. The aim was to evaluate their cytocompatibility, resistance to Staphylococcus aureus biofilm formation, and their potential to enhance the susceptibility of any biofilm formed to antibiotics. Using automated high-content screening confocal microscopy, biofilm formation of a clinical methicillin-resistant Staphylococcus aureus (MRSA) isolate expressing GFP was quantified, along with isogenic mutants that were unable to form polysaccharidic or proteinaceous biofilm matrices. The results showed that PEGylated-PDLLA coatings exhibited significant antibiofilm properties, with M showing the highest effect. This inhibitory effect was stronger in S. aureus biofilms with a matrix composed of proteins compared to those with an exopolysaccharide (PIA) biofilm matrix. Our data suggest that the antibiofilm effect may have been due to (i) inhibition of the initial attachment through microbial surface components recognising adhesive matrix molecules (MSCRAMMs), since PEG reduces protein surface adsorption via surface hydration layer and steric repulsion; and (ii) mechanical disaggregation and dispersal of microcolonies due to the bioresorbable/degradable nature of the polymers, which undergo hydration and hydrolysis over time. The disruption of biofilm morphology by the PDLLA-PEG co-polymers increased S. aureus susceptibility to antibiotics like rifampicin and fusidic acid. Adding 1 % AgSD provided additional early bactericidal effects on both biofilm and planktonic S. aureus. Additionally, the coatings were cytocompatible with immune cells, indicating their potential to enhance bacterial clearance and reduce bacterial colonisation of titanium-based orthopaedic biomaterials.

Purpose: Mask selection could affect an individual's experience with positive airway pressure (PAP) treatment for obstructive sleep apnea, but there is very limited data on the impact of switching to a different mask once established on PAP therapy. This study investigated the patient's experience when switching from a previous-generation PAP mask to a new-generation mask via remote care. Methods: A new-generation mask (AirFit F30i or AirFit N30i) was successfully fitted to 215 participants during video conferencing sessions. Participants completed online questionnaires on day 1, day 3, day 7, day 30 and day 90 after mask switch to collect subjective feedback and quality of life data; objective PAP device data were also downloaded. Results: Residual apnea-hypopnea index showed statistically significant difference from baseline at day 30 (+0.2 ± 0.9/h [p = 0.026]) and day 90 (+0.2 ± 0.8/h [p = 0.006]), however unlikely to be clinically relevant. Average daily usage was significantly increased from baseline at day 30 (+0.2 ± 1.2 h/day [p = 0.010]) but not day 90 (+0.1 ± 1.0 h/day [p = 0.126]). Functional Outcomes of Sleep Questionnaire (FOSQ-10) score was significantly higher at day 90 (change from baseline to day 90: +0.48 ± 2.29 [p = 0.015]). Subjective ratings for comfort, seal, and usability of the new-generation mask were significantly better than the predefined acceptability level. Rates of PAP-related side effects were generally acceptable. Conclusion: Remote management of mask change was associated with good outcomes in terms of objective device data and patient acceptability. This approach could be used to improve the overall therapy experience for individuals requiring a PAP therapy mask change for any reason. Clinical trial registration: http://clinicaltrials.gov (NCT05262439).

Contemporary scientific discussions are increasingly focusing on Akkermansia muciniphila due to its complex influence on intestinal physiology. This article provides a comprehensive analysis of the various effects Akkermansia muciniphila has on intestinal inflammation, while also exploring its potential associations with obesity and cardiovascular diseases. A systematic literature search was conducted using PubMed, Google Scholar, and ResearchGate with the following keywords: Akkermansia muciniphila, obesity, cardiovascular risk, and inflammatory bowel diseases. The aim of our mini-review was to examine the impact of Akkermansia bacteria on the intestines, cardiovascular system, and its relationship with obesity. Through a detailed review of current literature, the article seeks to elucidate the complex interactions of Akkermansia muciniphila within the human body, highlighting its potential contributions to health improvement and medical interventions. Research indicates that Akkermansia muciniphila positively correlates with maintaining intestinal health, modulating the cardiovascular system, and aiding in weight management. However, the number of studies available is small, and the effects of Akkermansia muciniphila on human health require further research.

Abstract Subduction interfaces exhibit various slip styles, including slow slip events (SSEs). We use a micromechanics‐based approach to calculate the effective rheology of a shear zone containing ellipsoidal amphibolite clasts deforming by dislocation creep within an interconnected linear‐viscous phyllosilicate‐dominated matrix. Frictional failure occurs if local stress exceeds Mohr‐Coulomb yield strength. At moderate fluid overpressure, mixed‐frictional‐viscous behavior emerges at ∼350–560°C, consistent with a broad zone of mixed fault slip behavior without requiring extreme fluid overpressures. Increasing stress in this transition zone promotes local frictional failure and raises bulk strain rate. If, however, the bulk strain rate increases by more than one order of magnitude, system‐wide frictional sliding becomes preferable. This strain rate increase is insufficient to explain the slip rates observed in geophysically detectable SSEs. Therefore, viscous matrix flow as modeled here cannot explain SSEs without either invoking dynamic weakening within a frictional‐viscous flow or a mechanism switch to dominantly frictional sliding.

Diffusion-weighted magnetic resonance imaging (DMRI) is a potential tool to assess changes in brain connectivity and microstructure resulting from physical and occupational therapy in young children with cerebral palsy. This works was carried out to assess whether DMRI can detect changes after 36 weeks of physical and occupational therapy in the microstructure and connectivity of the brains of children with cerebral palsy and determine whether imaging findings correlate with changes in clinical measures of motor function. Five children underwent anatomical MRI and DMRI and evaluations of motor function skills at baseline and after 36 weeks of intensive or once-weekly physical and occupational Perception-Action Approach therapies. Diffusion tensor imaging and constrained spherical deconvolution methods were used to calculate fractional anisotropy (FA) and fiber orientation distribution functions (fODFs), respectively. The fODFs were used to generate tractograms of the cerebrospinal tract (CST). After 36 weeks of physical and occupational therapy, all children showed increases in motor function. No changes were observed in anatomical MRI before and after therapy but CST tractography did show small differences indicating possible altered microstructure and connectivity in the brain. FA values along the CSTs, however, showed no significant changes. Reliable longitudinal DMRI can be employed in toddler-aged children with CP and DMRI has the potential to monitor neuroplastic changes in white matter microstructure. However, there is a high variability between subjects and clinical improvements were not always correlated with measures of FA along the CST.

Abstract The Eurasian Bronze Age (BA) has been described as a period of substantial human migrations, the emergence of pastoralism, horse domestication, and development of metallurgy. This study focuses on two north Eurasian sites sharing Siberian genetic ancestry. One of the sites, Rostovka, is associated with the Seima-Turbino (ST) phenomenon (~2200-1900 BCE) that is characterized by elaborate metallurgical objects found throughout Northern Eurasia. The genetic profiles of Rostovka individuals vary widely along the forest-tundra Siberian genetic cline represented by many modern Uralic-speaking populations, and the genetic heterogeneity observed is consistent with the current understanding of the ST being a transcultural phenomenon. Individuals from the second site, Bolshoy Oleni Ostrov in Kola, in comparison form a tighter cluster on the Siberian ancestry cline. We further explore this Siberian ancestry profile and assess the role of the ST phenomenon and other contemporaneous BA cultures in the spread of Uralic languages and Siberian ancestry.

Abstract The Johns Hopkins Learning Environment Scale (JHLES) was developed by Robert B. Shochet, Jorie M. Colbert and Scott M. Wright of the Johns hopkins university school of medicine and consists of 28 items used to evaluate perception of the academic environment. The objective was to translate and adapt the JHLES to Polish cultural conditions and to validate the Polish version of the tool. The JHLES questionnaire was completed by students of all years (first–fifth) of the faculties of dental medicine at the Medical University of Lublin and the Medical University of Gdańsk. The total surveyed population consisted of 597 students. The overall reliability of the tool was excellent. Confirmatory factor analysis was performed in order to confirm structural consistency with the original JHLES tool. Consequently, all indices had acceptable values (close to 1 or 0, depending on the case), and there was consistency in the results, which shows that the JHLES model is supported by the data. In the present study, the JHLES has been validated in a sample of dental students for the first time in Poland and Europe. Our study provided good evidence for the reliability and validity of the Polish version of the JHLES. In conclusion, the Polish-language version of the JHLES questionnaire is a reliable and valid instrument for analysing the learning environment for students, and its factor structure is supported by the data.

While there has been significant progress in controlling falciparum malaria in the Lao People's Democratic Republic (PDR), sporadic cases persist in southern provinces where the extent and patterns of transmission remain largely unknown. To assess parasite transmission in this area, 53 Plasmodium falciparum (Pf) positive cases detected through active test and treat campaigns from December 2017 to November 2018 were sequenced, targeting 204 highly polymorphic amplicons. Two R packages, MOIRE and Dcifer, were applied to assess the multiplicity of infections (MOI), effective MOI (eMOI), within-host parasite relatedness, and between-host parasite relatedness ([Formula: see text]). Genomic data were integrated with survey data to characterize the temporal and spatial structures of identified clusters. The positive cases were mainly captured during the focal test and treat campaign conducted in 2018, and in the Pathoomphone area, which had the highest test positivity and forest activity. About 30% of the cases were polyclonal infections, with over half of theses (63%) showing within-host relatedness greater than 0.6, suggesting that cotransmission rather than superinfection was primarily responsible for maintaining polyclonality. A large majority of cases (81%) were infected by parasites genetically linked to one or more other cases. We identified five genetically distinct clusters in forest fringe villages within the Pathoomphone district, characterized by a high degree of genetic relatedness between parasites (mean [Formula: see text] = 0.8). Four smaller clusters of 2-3 cases linked Moonlapamok and Pathoomphone districts, with an average [Formula: see text] of 0.6, suggesting cross-district transmission. Most of the clustered cases occurred within 20 km and 2 months of each other, consistent with focal transmission. Transmission clusters identified in this study confirm the role of ongoing focal parasite transmission occurring within the forest or forest-fringe in the highly mobile population.

This paper examines two competing approaches to the study of addiction: the neuroscientific model which conceives of addiction as a brain disease, and the phenomenological critique of neuroscience, which appeals to lived experience. I employ Gadamer’s rich hermeneutic contribution to the phenomenological tradition in order to generate more fruitful dialogue between these competing models. Gadamer’s critique of the leveling of language in science is employed to counter neuroscientific claims to objectivity, while his redescription of the constructive role of prejudice in understanding is employed to highlight inadequacies in the phenomenological critique of neuroscience. Ultimately, I propose a fusion of these contested horizons which can generate richer clinical practice—reimagining the role of addiction recovery as helping individuals interpret and understand their experience of addiction toward new ways of being in the world.

Neonatal male circumcision is a commonly performed procedure in the United States. Circumcisions are performed at various ages by a variety of clinical providers for multiple reasons, including religious, cultural, personal, and medical indications. In the United States, neonatal circumcision is routinely performed by non-urologic providers in the hospital within the first few days of life or as a religious ceremony on the 8th day of life. If neonatal circumcision is deferred in the hospital and subsequently not performed in the outpatient setting, it is then typically performed in the operating room under general anesthesia after 6 months of life. Neonatal circumcision is supported by both the American Academy of Pediatrics (AAP) and the American College of Obstetricians and Gynecologists (ACOG) due to the belief that the health benefits outweigh the minimal risk of the procedure. Despite this, neonatal circumcision rates have decreased in the United States in recent decades, in part due to access to the procedure, often related to changing insurance coverage. This has led to increased rates of operative circumcisions. Operative circumcisions are more costly to the healthcare system, subject the patient to cardiopulmonary and potentially neurotoxic effects of general anesthesia, and carry an increased environmental footprint, compared to neonatal circumcision. The intention of this paper is not to promote or justify circumcision for all patients, but rather to compare the clinical and environmental impact of neonatal versus operative circumcisions.

Abstract Cattle herders and agricultural workers have been identified has key high-risk populations for malaria in northern Namibia. Population size estimates for these groups are lacking but are important for planning, monitoring and evaluating the effectiveness of targeted strategies towards malaria elimination in the region. In this analysis, we extend population size estimation methods routinely used in HIV research, specifically social mapping and multiple source capture-recapture, to the context of malaria to estimate how many cattle herders and agricultural workers lived in two regions of northern Namibia over the course of the 2019–2020 malaria season. Both methods estimated two to three times more agricultural workers than cattle herders but size estimates based on the multiple source capture-recapture method were two to three times greater than the mapping-based, highlighting important methodological considerations to apply such methods to these highly mobile populations. In particular, we compared open versus closed populations assumptions for the capture-recapture method and assessed the impact of sensitivity analyses on the procedure to link records across multiple data sources on population size estimates. Our results are important for national control programs to target their resources and consider integrating routine population size estimation of high risk populations in their surveillance activities.

Abstract Aneuploidies, and in particular, trisomies represent the most common genetic aberrations observed in human genetics today. To explore the presence of trisomies in historic and prehistoric populations we screen nearly 10,000 ancient human individuals for the presence of three copies of any of the target autosomes. We find clear genetic evidence for six cases of trisomy 21 (Down syndrome) and one case of trisomy 18 (Edwards syndrome), and all cases are present in infant or perinatal burials. We perform comparative osteological examinations of the skeletal remains and find overlapping skeletal markers, many of which are consistent with these syndromes. Interestingly, three cases of trisomy 21, and the case of trisomy 18 were detected in two contemporaneous sites in early Iron Age Spain (800-400 BCE), potentially suggesting a higher frequency of burials of trisomy carriers in those societies. Notably, the care with which the burials were conducted, and the items found with these individuals indicate that ancient societies likely acknowledged these individuals with trisomy 18 and 21 as members of their communities, from the perspective of burial practice.

Abstract Background The STRUCTURE software has gained popularity as a tool for population structure and genetic analysis. Nevertheless, formatting data to meet STRUCTURE's specific requirements can be daunting and susceptible to errors, especially when handling multilocus data. This article highlights the creation of a graphical user interface (GUI) application tailored to streamline the process of converting multiple sequence alignments into a single, cohesive file that is compatible with the STRUCTURE software. Results The application has been developed utilizing Tkinter for the GUI and Biopython for handling FASTA files. This program processes the files, pinpoints variable sites, and converts the sequences into a binary format. Subsequently, the sequences are concatenated and presented within the graphical interface's text area, enabling users to review and confirm the results. Furthermore, the program stores the concatenated results in a file, delivering a ready-to-use input for the STRUCTURE software. Conclusion This application offers an efficient and dependable solution for transforming multiple aligned FASTA files into a concatenated binary format file, which is compatible with the STRUCTURE software. With its user-friendly graphical interface and error-reduction approach, this tool proves invaluable for researchers engaged in population structure and genetic analysis.

Many organizations are developing connected worker and digital twin solutions in mixed reality as a means to quickly train new hires while simultaneously developing assistive deep learning models for quality-control mechanisms through internal documentation, diagrams, and 3D models. However, the transformation of real-life assets and processes into digital twin counterparts is a multi-step, intensive undertaking, requiring significant domain expertise and technical know-how. Therefore, we explore the architectural and technical components required to transform the most critical assets into a digital twin that yields immediate business value. Specifically, we explore the creation of digitalization architectures with re-usable components for training not only new hires but also deep neural network-based computer vision models. In this work, we present an action research case study guided by the Project Management Body of Knowledge framework. This case study was conducted in coordination with TechnipFMC, a global leader oil and gas company, on the digitalization efforts to transition into their industrial metaverse. We developed multiple architectures to bring assembly practices into a mixed reality training solution usable by trainees and editable by domain experts in real time. Further, we generate synthetic data from the same mixed reality training environments to train object detection models on industrial components and find that the photorealistic 3D models can improve mean average precision on the real-world task by +2.5 mAP.

Abstract Background A major challenge to malaria elimination is identifying and targeting populations that are harbouring residual infections and contributing to persistent transmission. In many near-elimination settings in Southeast Asia, it is known that forest-goers are at higher risk for malaria infection, but detailed information on their behaviours and exposures is not available. Methods In Aceh Province, Indonesia, a near-elimination setting where a growing proportion of malaria is due to Plasmodium knowlesi, a case–control study was conducted to identify risk factors for symptomatic malaria, characteristics of forest-goers, and key intervention points. From April 2017 to September 2018, cases and controls were recruited and enrolled in a 1:3 ratio. Cases had confirmed malaria infection by rapid diagnostic test or microscopy detected at a health facility (HF). Gender-matched controls were recruited from passive case detection among individuals with suspected malaria who tested negative at a health facility (HF controls), and community-matched controls were recruited among those testing negative during active case detection. Multivariable logistic regression (unconditional for HF controls and conditional for community controls) was used to identify risk factors for symptomatic malaria infection. Results There were 45 cases, of which 27 were P. knowlesi, 17 were Plasmodium vivax, and one was not determined. For controls, 509 and 599 participants were recruited from health facilities and the community, respectively. Forest exposures were associated with high odds of malaria; in particular, working and sleeping in the forest (HF controls: adjusted odds ratio (aOR) 21.66, 95% CI 5.09–92.26; community controls: aOR 16.78, 95% CI 2.19–128.7) and having a second residence in the forest (aOR 6.29, 95% CI 2.29–17.31 and 13.53, 95% CI 2.10–87.12). Male forest-goers were a diverse population employed in a variety of occupations including logging, farming, and mining, sleeping in settings, such as huts, tents, and barracks, and working in a wide range of group sizes. Reported use of protective measures, such as nets, hammock nets, mosquito coils, and repellents was low among forest-goers and interventions at forest residences were absent. Conclusions Second residences in the forest and gaps in use of protective measures point to key malaria interventions to improve coverage in forest-going populations at risk for P. knowlesi and P. vivax in Aceh, Indonesia. Intensified strategies tailored to specific sub-populations will be essential to achieve elimination.

To compare the capacity of native and exotic vine species established under a rainforest canopy, a comparison of growth rates and resource allocation was made amongst five exotic vine species that are serious and common invaders and two common native vine species under two light conditions reflective of edge and interior canopy conditions. All species experienced heavy reductions in growth parameters in the low-light treatment, but three exotic species showed stronger growth under the low light. All exotic species had higher plasticity in leaf morphology showing a significant increase in SLA under low light. Native vines may have a lower capacity to change leaf morphology in shade, as a result of local adaptation to edge habitats. Higher SLA under both low and high light conditions suggests that exotic vines species are able to exploit a range of forest conditions better than the native species. Three species, Anredera cordifolia, Araujia sericifera and Cardiospermum grandiflorum, appear particularly capable of invading rainforest interiors. Individuals produced few leaves, focusing resources on roots and stems suggesting a response to reach the canopy quickly. With their long-distance seed dispersal, plasticity in leaf SLA and high RGR, these species appear most likely to invade undisturbed rainforest.

Our purpose in this paper is to throw light on the tension, or even internal conflict, tertiary-level students experience when they struggle to negotiate the rhetorical norms of disciplinary writing and the changes in their authorial voice that necessarily occur in this socialization process. With this goal in mind, we designed and conducted the study to gain insights into the perceptions Management and English Philology students have as to what constitutes a convincing authorial voice and the discourse-level features employed to realize this. Twenty-six study participants created a diverse group with regards to nationality, gender, study level, disciplinary affiliation and cultural and linguistic background. Their evaluations of voice were first analyzed from their responses to a questionnaire and then expanded through interviews. The findings reveal that a reader-inclusive voice, which requires the use of de-jargonized language, clear purpose and structure, and creates room for reader’s own interpretation, is crucial for a text to be convincing. We also argue that students’ preference for reader-sensitive academic writing should be supported and encouraged through the provision of strategic academic writing pedagogy.

The purpose of this paper is to identify the optimal XR tools for cultivating inclusion in a second language classroom that Polish language teachers know and successfully use and which female refugees from Ukraine would like to use. The article is grounded in a project aimed at bridging the substantial gap between refugee women and women with fewer opportunities within the realm of language education. It is acknowledged that women with fewer opportunities (such as migrants, refugees, and asylum seekers) have already coped with significant challenges related to relocation and other traumatic experiences. The project posits that XR tools can be employed to assist these women in acquiring new language skills. The central objective is to establish an XR environment that alleviates additional anxieties associated with Foreign Language Learning (FLL). By offering a broader array of realistic and engaging scenarios, these XR learning environments can facilitate practical activities. Such environments enable students to familiarize themselves with the nuances of language use and develop proficiency beyond the confines of a classroom setting. This approach emphasizes language application rather than rote memorization of closed-system rules. Moreover, the work focuses on standardizing terminology and methodologies through comprehensive literature and Internet research. Finally, the report highlights the latest advancements in Poland concerning the discussed issue. The project posits that XR tools can be employed to assist these women in acquiring new language skills. The central objective is to establish an XR environment that alleviates additional anxieties associated with Foreign Language Learning (FLL). By offering a broader array of realistic and engaging scenarios, these XR learning environments can facilitate practical activities. Such environments enable students to familiarize themselves with the nuances of language use and develop proficiency beyond the confines of a classroom setting. This approach emphasizes language application rather than rote memorization of closed-system rules. Moreover, the work focuses on standardizing terminology and methodologies through comprehensive literature and Internet research. Finally, the report highlights the latest advancements in Poland concerning the discussed issue.

BackgroundA number of studies have detected relationships between weather and diarrhea. Few have investigated associations with specific enteric pathogens. Understanding pathogen-specific relationships with weather is crucial to inform public health in low-resource settings that are especially vulnerable to climate change.ObjectivesOur objectives were to identify weather and environmental risk factors associated with diarrhea and enteropathogen prevalence in young children in rural Bangladesh, a population with high diarrheal disease burden and vulnerability to weather shifts under climate change.MethodsWe matched temperature, precipitation, surface water, and humidity data to observational longitudinal data from a cluster-randomized trial that measured diarrhea and enteropathogen prevalence in children 6 months-5.5 years from 2012-2016. We fit generalized additive mixed models with cubic regression splines and restricted maximum likelihood estimation for smoothing parameters.ResultsComparing weeks with 30°C versus 15°C average temperature, prevalence was 3.5% higher for diarrhea, 7.3% higher for Shiga toxin-producing Escherichia coli (STEC), 17.3% higher for enterotoxigenic E. coli (ETEC), and 8.0% higher for Cryptosporidium. Above-median weekly precipitation (median: 13mm; range: 0-396mm) was associated with 29% higher diarrhea (adjusted prevalence ratio 1.29, 95% CI 1.07, 1.55); higher Cryptosporidium, ETEC, STEC, Shigella, Campylobacter, Aeromonas, and adenovirus 40/41; and lower Giardia, sapovirus, and norovirus prevalence. Other associations were weak or null.DiscussionHigher temperatures and precipitation were associated with higher prevalence of diarrhea and multiple enteropathogens; higher precipitation was associated with lower prevalence of some enteric viruses. Our findings emphasize the heterogeneity of the relationships between hydrometeorological variables and specific enteropathogens, which can be masked when looking at composite measures like all-cause diarrhea. Our results suggest that preventive interventions targeted to reduce enteropathogens just before and during the rainy season may more effectively reduce child diarrhea and enteric pathogen carriage in rural Bangladesh and in settings with similar meteorological characteristics, infrastructure, and enteropathogen transmission.

Objectives To examine inequalities in birth before arrival (BBA) at hospitals in South West England, understand which groups are most likely to experience BBA and how this relates to hypothermia and outcomes (phase A). To investigate opportunities to improve temperature management advice given by emergency medical services (EMS) call-handlers during emergency calls regarding BBA in the UK (phase B).Design A two-phase multimethod study. Phase A analysed anonymised data from hospital neonatal records between January 2018 and January 2021. Phase B analysed anonymised EMS call transcripts, followed by focus groups with National Health Service (NHS) staff and patients.Setting Six Hospital Trusts in South West England and two EMS providers (ambulance services) in South West and North East England.Participants 18 multidisciplinary NHS staff and 22 members of the public who had experienced BBA in the UK.Results 35% (64/184) of babies conveyed to hospital were hypothermic on arrival. When compared with national data on all births in the South West, we found higher percentages of women with documented safeguarding concerns at booking, previous live births and ‘late bookers’ (booking their pregnancy >13 weeks gestation). These women may, therefore, be more likely to experience BBA. Preterm babies, babies to first-time mothers and babies born to mothers with disability or safeguarding concerns at booking were more likely to be hypothermic following BBA. Five main themes emerged from qualitative data on call-handler advice: (1) importance placed on neonatal temperature; (2) advice on where the baby should be placed following birth; (3) advice on how to keep the baby warm; (4) timing of temperature management advice and (5) clarity and priority of instructions.Conclusions Findings identified factors associated with BBA and neonatal hypothermia following BBA. Improvements to EMS call-handler advice could reduce the number of babies arriving at hospital hypothermic.

IntroductionThis paper deals with the question on how sport performances may be influenced by internal, emotional processes, which stem from outside feedback.MethodsIn terms of methods, players’ subjective performance ratings for four experimental auditory cue conditions were examined; these included both ‘positive’ and ‘negative’ stadium noise, ‘no (auditory) conditions,’ and a control/‘baseline’ condition. This resulted in a qualitative-analytic data set that was obtained succeeding each auditory cue condition using a unique football training machine (i.e., known as ‘Footbonaut’). Without having received any coaching/performance feedback, players were asked to rate and individually comment on their perceived performance ratings for each experimental auditory condition.ResultsFindings indicate stronger and more significant correlations between auditory conditions and subjective ratings compared to the non-auditory condition and its subjective rating. Furthermore, data provides initial insight into players’ emotional experiences during each of the practice conditions.DiscussionThese noteworthy findings on players’ abilities to accurately judge their performances based on selfmonitoring and intrinsic feedback are discussed from an Ecological Dynamics perspective, linked to a Nonlinear Pedagogy for coaching. Here, representative and affective learning designs for skill learning and performance preparation are presented. Finally, a hypothetical catalyst effect of auditory stadium noise on subjective performance rating is proposed.

Abstract The spread of prion‐like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern that correlates with disease severity. Clinical observation combined with complementary experimental studies has shown that Tau preformed fibrils (PFF) are prion‐like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau. While several cell surface receptors of Tau are known, they are not specific to the fibrillar form of Tau. Moreover, the underlying cellular mechanisms of Tau PFF spreading remain poorly understood. Here, it is shown that the lymphocyte‐activation gene 3 (Lag3) is a cell surface receptor that binds to PFF but not the monomer of Tau. Deletion of Lag3 or inhibition of Lag3 in primary cortical neurons significantly reduces the internalization of Tau PFF and subsequent Tau propagation and neuron‐to‐neuron transmission. Propagation of Tau pathology and behavioral deficits induced by injection of Tau PFF in the hippocampus and overlying cortex are attenuated in mice lacking Lag3 selectively in neurons. These results identify neuronal Lag3 as a receptor of pathologic Tau in the brain，and for AD and related Tauopathies, a therapeutic target.

ABSTRACT: Objectives: To (i) develop a methodology for using historical and comparative perspectives to inform policy and (ii) provide evidence for antimicrobial-resistance (AMR) policymaking by drawing on lessons from climate change and tobacco control. Methods: Using a qualitative design, we systematically examined two other complex, large-scale policy issues—climate change and tobacco control—to identify what relevance to AMR can be learned from how these issues have evolved over time. During 2018–2020, we employed a five-stage approach to conducting an exploratory study involving a review of secondary historical analysis, identification of drivers of change, prioritisation of the identified drivers, scenario generation and elicitation of possible policy responses. We sought to disrupt more ‘traditional’ policy and research spaces to create an alternative where, stimulated by historical analysis, academics (including historians) and policymakers could come together to challenge norms and practices and think creatively about AMR policy design. Results: An iterative process of analysis and engagement resulted in lessons for AMR policy concerning persistent evidence gaps and uncertainty, the need for cross-sector involvement and a collective effort through global governance, the demand for new interventions through more investment in research and innovation, and recognising the dynamic relationship between social change and policy to change people's attitudes and behaviours are crucial towards tackling AMR. Conclusion: We draw on new methodological lessons around the pragmatism of future- and policy-oriented approaches incorporating robust historical and comparative analysis. The study demonstrates proof of concept and offers a reproducible method to advance further methodology, including transferrable policies that could tackle health problems, such as AMR.

Abstract Background In 2020, the Zambia National Malaria Elimination Centre targeted the distribution of long-lasting insecticidal nets (LLINs) and indoor-residual spraying (IRS) campaigns based on sub-district micro-planning, where specified geographical areas at the health facility catchment level were assigned to receive either LLINs or IRS. Using data from the 2021 Malaria Indicator Survey (MIS), the objectives of this analysis were to (1) assess how well the micro-planning was followed in distributing LLINs and IRS, (2) investigate factors that contributed to whether households received what was planned, and (3) investigate how overall coverage observed in the 2021 MIS compared to the 2018 MIS conducted prior to micro-planning. Methods Households’ receipt of ≥ 1 LLIN, and/or IRS within the past 12 months in the 2021 MIS, was compared against the micro-planning area under which the households fell. GPS points for 3,550 households were overlayed onto digitized micro-planning maps in order to determine what micro-plan the households fell under, and thus whether they received their planned intervention. Mixed-effects regression models were conducted to investigate what factors affected whether these households: (1) received their planned intervention, and (2) received any intervention. Finally, coverage indicators between the 2021 and 2018 MIS were compared. Results Overall, 60.0% (95%CI 55.4, 64.4) of households under a micro-plan received their assigned intervention, with significantly higher coverage of the planned intervention in LLIN-assigned areas (75.7% [95%CI 69.5, 80.9]) compared to IRS-assigned areas (49.4% [95%CI: 44.4, 54.4]). Regression analysis indicated that households falling under the IRS micro-plan had significantly reduced odds of receiving their planned intervention (OR: 0.34 [95%CI 0.24, 0.48]), and significantly reduced odds of receiving any intervention (OR: 0.51 [95%CI 0.37, 0.72] ), compared to households under the LLIN micro-plan. Comparison between the 2021 and 2018 MIS indicated a 27% reduction in LLIN coverage nationally in 2021, while IRS coverage was similar. Additionally, between 2018 and 2021, there was a 13% increase in households that received neither intervention. Conclusions This analysis shows that although the micro-planning strategy adopted in 2020 worked much better for LLIN-assigned areas compared to IRS-assigned areas, there was reduced overall vector control coverage in 2021 compared to 2018 before micro-planning.

Abstract Background The importation of parasites across borders remains a threat to malaria elimination. The Southern African Development Community Malaria Elimination Eight (E8) established 39 border health facilities on 5 key international borders between high and low-burden countries. These clinics aimed to improve access to prevention, diagnosis, and treatment of malaria for residents in border areas and for mobile and migrant populations who frequently cross borders. Studies were conducted in each of the four high-burden E8 countries (Angola, Mozambique, Zambia, and Zimbabwe) to evaluate malaria services in border areas. Methods Cross-sectional surveys were conducted within 30 km of recently established E8 Border Health Posts. Structured questionnaires were administered to randomly selected respondents to assess malaria-related knowledge and behavior, access to malaria prevention, diagnosis and treatment of malaria, and risk factors for malaria associated with local and cross-border travel. Results Results showed that most providers followed appropriate guidelines performing blood tests when individuals presented with fever, and that nearly all those who reported a positive blood test received medication. Lack of access to health care due to distance, cost or mistrust of the provider was rare. A minority of respondents reported not receiving timely diagnosis either because they did not seek help, or because they were not offered a blood test when presenting with fever. There was a high level of correct knowledge of causes, symptoms, and prevention of malaria. A majority, of border residents had access to primary prevention against malaria through either long-lasting insecticidal nets (LLINs) or indoor residual spraying (IRS). Cross border travel was common with travellers reporting sleeping outside without protection against malaria. Conclusions The study demonstrated the importance of border health facilities in providing access to malaria services. Prevention needs to be improved for people who travel and sleep outdoors. Community health workers can play a key role in providing access to information, testing and treating malaria.

Abstract Heart rate (HR) is a crucial physiological signal that can be used to monitor health and fitness. Traditional methods for measuring HR require wearable devices, which can be inconvenient or uncomfortable, especially during sleep and meditation. Noncontact HR detection methods employing microwave radar can be a promising alternative. However, the existing approaches in the literature usually use high-gain antennas and require the sensor to face the user’s chest or back, making them difficult to integrate into a portable device and unsuitable for sleep and meditation tracking applications. This study presents a novel approach for noncontact HR detection using a miniaturized Soli radar chip embedded in a portable device (Google Nest Hub). The chip has a $$6.5 \text{ mm } \times 5 \text{ mm } \times 0.9 \text{ mm }$$ 6.5 mm × 5 mm × 0.9 mm dimension and can be easily integrated into various devices. The proposed approach utilizes advanced signal processing and machine learning techniques to extract HRs from radar signals. The approach is validated on a sleep dataset (62 users, 498 h) and a meditation dataset (114 users, 1131 min). The approach achieves a mean absolute error (MAE) of 1.69 bpm and a mean absolute percentage error (MAPE) of $$2.67\%$$ 2.67 % on the sleep dataset. On the meditation dataset, the approach achieves an MAE of 1.05 bpm and a MAPE of $$1.56\%$$ 1.56 % . The recall rates for the two datasets are $$88.53\%$$ 88.53 % and $$98.16\%$$ 98.16 % , respectively. This study represents the first application of the noncontact HR detection technology to sleep and meditation tracking, offering a promising alternative to wearable devices for HR monitoring during sleep and meditation.

The wide range of technological innovations took place in the post-millennium period and later became widely available have fundamentally reshaped the relationship between ICT infrastructure and business in the life of for-profit organizations. This is particularly true for the so-called primary (value-creating) processes. These technologies that have fundamentally transformed the way business organizations operate are collectively referred to as "Industry 4.0" technologies. A significant group of these technologies are the cloud-based solutions. By using these solutions, the users can get benefits from the ICT infrastructure through a third-party service. These services can be applications made available on a specific online interface (SaaS), or various platform elements (PaaS, for example: application servers, virtual servers, etc.) or infrastructure elements such as leased computing capacity (IaaS). By using cloud-based solutions, the customer can avoid the investment needed to run the ICT infrastructure and the additional problems rooted by the operation of ICT-infrastructure. A questionnaire survey was carried out in early 2019, in which 498 respondents voluntarily participated. The survey investigated the deployment level of ICT infrastructure among SMEs in Hungary, its information security consequences and how the management of the for-profit organizations evaluate the contribution of ICT infrastructure to the success of their business. The use of different cloud-based solutions was also measured in the mentioned questionnaire. The paper presents the research results of the prevalence of use of different cloud solutions with similar studies in the region. Furthermore, it examines whether cloud solutions have individually detectable beneficial effects on business operations, and whether synergies can be identified when multiple cloud applications are used together. Based on the qualitative results of the research and their interpretation, a broader analysis has been offered.

Abstract Background Global interest in malaria elimination has prompted research on active test and treat (TaT) strategies. Methods A systematic review and meta-analysis were conducted to assess the effectiveness of TaT strategies to reduce malaria transmission. Results A total of 72 empirical research and 24 modelling studies were identified, mainly focused on proactive mass TaT (MTaT) and reactive case detection (RACD) in higher and lower transmission settings, respectively. Ten intervention studies compared MTaT to no MTaT and the evidence for impact on malaria incidence was weak. No intervention studies compared RACD to no RACD. Compared to passive case detection (PCD) alone, PCD + RACD using standard diagnostics increased infection detection 52.7% and 11.3% in low and very low transmission settings, respectively. Using molecular methods increased this detection of infections by 1.4- and 1.1-fold, respectively. Conclusion Results suggest MTaT is not effective for reducing transmission. By increasing case detection, surveillance data provided by RACD may indirectly reduce transmission by informing coordinated responses of intervention targeting.

Abstract Aim The aim of our study was to translate and adapt the Dundee Ready Education Environment Measure (DREEM) questionnaire developed by Roff et al. to the cultural conditions in Poland and also to validate it. Studying the learning environment is beneficial because it can identify students’ perceptions of their environment and support the staff in reflecting on, planning for and combining proper teaching approaches to improve it. Methods The DREEM questionnaire was completed by students of all years (first–fifth) in the faculties of dental medicine at the Medical University of Lublin and the Medical University of Gdańsk. The total surveyed population consisted of 650 students. Validity was separated into four phases: (1) translation validity, (2) confirmatory factor analysis, (3) concurrent validity and (4) criterion-related validity. Results Our study confirmed the original structure of the DREEM tool (GFI = 0.955, AGFI = 0.951, NFI = 0.931, TLI = 0.962, CFI = 0.964, RNI = 0.964, IFI = 0.964, RFI = 0.928, PNFI = 0.885, SRMR = 0.062, RMSEA = 0.043, 90% CI = 0.041–0.046) and obtained very good reliability rates, with Cronbach’s alpha > 0.7 for all scales. Only Subscale V achieved a lower Cronbach’s alpha of > 0.5. The study was conducted using the test–retest method, which is why the intraclass correlation coefficients for reliability were also calculated; individual items showed both medium and good correspondence. Conclusions Our study provided good evidence for the reliability and validity of the Polish version of the DREEM. In conclusion, the Polish-language version of the DREEM questionnaire is a reliable and valid instrument for analysing the learning environment for dental students and its factor structure is supported by the data.

Amphibians and reptiles are among the most endangered organisms worldwide - respectively about 35% and 20% (IUCN, 2022). Their vulnerability is related to the insufficiency of ecologically optimal habitats (climatic, physico-chemical, biocenotic) for development and reproduction. The 9 species of amphibians and 7 reptiles from in the Lower Prut Area, present important ecological links in the ecosystems specific to the given area, and 5 and 3 species, respectively, are included in the Red Book of the Republic of Moldova (2015). Thus, Pelobates fuscus is Critically Endangered (CR), and pollution, and especially the drying up of lakes, would lead to the extinction of the species. The vulnerable species (VU) of Triturus cristatus and Lissotriton vulgaris will be quite affected, both by desiccation and by the lack of oxygen during the summer period. The species Bombina bombina, Hyla orientalis, Pelophylax ridibundus,Pelophylax lessonae and Bufo viridis have a wider ecological valence, which makes them less threatened by climate change, but remain linked to waters for reproduction. Reptiles prefer shady, moist, swampy, aquatic habitats, etc., but they also need sufficiently sunny places. The 3 endangered species (EN), such as Emys orbicularis, although it is omnivorous, is very rarely encountered (RR); the species of Podarcis taurica, Coluber caspius, Lacerta agilis, Lacerta viridis have a wider ecological valence and show a weak vulnerability to climate change, and the dependence on food resources of the Natrix natrix and Natrix tessellate makes them more vulnerable to the drying up of water bodies. In order to reduce the negative effects of climate change on vulnerable amphibians and reptiles, scientifically substantiated interventions are needed to rebuild habitats, to form ecological corridors connecting certain fragmented isoecohabitats, to expand the areas occupied by threatened species in various sectors, both with optimal conditions, as well as at the limit of extremes.

Each organism is characterized by a specific potential capacity to react to the influence of environmental factors, according to its genetic constitution and hereditary reaction norm. Some species can withstand large variations, others, on the contrary, very small, i.e. ecological valence is the amplitude of the variations of the conditions of existence between which a species is able to live. The totality of ecological valences constitutes the ecological spectrum of the species. In the context of the increasingly obvious manifestations, both of the climate change scenarios and the maintenance of the high level of pollution, especially with SO2, whole associations of some species of stenoic lichens may be threatened with extinction. Important is the conservation of ecobioindicator species that ensure non-instrumental ecological monitoring, promoted by the international Conventions. As a result of field expeditions from 2011-2018, 9 forest-petrophyte ecosystems were evaluated in the bordering area of the Dniester River, on the middle course segment, right bank. The altitude of the territory varies from 280-140 m, in the north, to 80-40 m, in the south. The exposure of the studied ecosystems is dominated by the northern orientation, favorable for the development of lichens. In the forest-petrophitic ecosystems the lichens from 9 protected areas belonging to 34 species were recorded. Of these 12 are rare species). It was established that for 10 species the ecological valences to the substrate, illumination and humidity are very narrow, so the ecological spectrum is very narrow. Among the 10 stenoic species 2 are included in the Red Book and 8 are Rare, so these will be the first affected in the case of changes in the environmental components.

Abstract Background Reactive case detection (RACD) or testing and treatment of close contacts of recent malaria cases, is commonly practiced in settings approaching malaria elimination, but standard diagnostics have limited sensitivity to detect low level infections. Reactive drug administration (RDA), or presumptive treatment without testing, is an alternative approach, but better understanding regarding community acceptability and operational feasibility are needed. Methods A qualitative study was conducted as part of a two-arm cluster randomized-controlled trial evaluating the effectiveness of RDA targeting high-risk villages and forest workers for reducing Plasmodium vivax and P. falciparum malaria in Thailand. Key informant interviews (KIIs) and focus group discussions (FGDs) were conducted virtually among key public health staff, village health volunteers (VHVs), and household members that implemented or received RDA activities. Transcriptions were reviewed, coded, and managed manually using Dedoose qualitative data analysis software, then underwent qualitative content analysis to identify key themes. Results RDA was well accepted by household members and public health staff that implemented it. RDA participation was driven by fear of contracting malaria, eagerness to receive protection provided by malaria medicines, and the increased access to health care. Concerns were raised about the safety of taking malaria medicines without having an illness, particularly if underlying health conditions existed. Health promotion hospital (HPH) staff implementing RDA noted its operational feasibility, but highlighted difficulty in traveling to remote areas, and requested additional travel resources and hiring more VHVs. Other challenges were highlighted including the need for additional training for VHVs on malaria activities and the inability of HPH staff to conduct RDA due to other health priorities (e.g., Covid-19). More training and practice for VHVs were noted as ways to improve implementation of RDA. Conclusions To maximize uptake of RDA, regular education and sensitization campaigns in collaboration with village leaders on the purpose and rationale of RDA will be critical. To alleviate safety concerns and increase participant safety, a rigorous pharmacovigilance program will be important. To accelerate uptake of RDA, trust between HPH staff and VHVs and the communities they serve must continue to be strengthened to ensure acceptance of the intervention. Trial registration This study was approved by the Committee on Human Research at the University of California San Francisco (19–28,060) and the local Ethics Committee for Research in Human Subjects at Tak Provincial Health office (009/63) and Kanchanaburi Provincial health office (Kor Chor 0032.002/2185). Local authorities and health officers in the provinces, districts, and villages agreed upon and coordinated the implementation of the study. All methods in this study were carried out in accordance with relevant guidelines and regulations.

Metastable Ti–Nb alloys are promising bone-implant materials due to improved mechanical biofunctionality and biocompatibility. To overcome increasing bacterial infection risk, alloying with antibacterial elements is a promising strategy. This study investigates the effect of minor gallium (Ga) additions (4, 8 wt% Ga) to as-cast and solution-treated β-type Ti–45Nb-based alloy (96(Ti–45Nb)-4Ga, 92(Ti–45Nb)-8Ga (wt.%)) on corrosion and passive film properties, as well as cytocompatibility and antibacterial activity. The electrochemical properties were evaluated by potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and Mott-Schottky analyses in phosphate-buffered saline (PBS). X-ray photoelectron spectroscopy (XPS) was performed to analyze the chemical composition of passive films. Early adhesion and viability of macrophages and Staphylococcus aureus were assessed by nucleocounting and colony-forming unit counting, respectively. The results showed that high corrosion resistance and passive film properties of Ti–45Nb are retained and even slightly improved with Ga. EIS results revealed that Ga addition improves the passive film resistance. XPS measurements of 92(Ti–45Nb)-8Ga show that the passive film contains Ti-, Nb- and Ga-based oxides, implying the formation of mixed (Ti–Nb-Ga) oxides. In addition, marginal Ga ion release rate was detected under free corrosion conditions. Therefore, it can be assumed that Ga species may contribute to passive film formation on Ga-containing alloys. The 92(Ti–45Nb)-8Ga elicited an antibacterial effect against S. aureus compared to cp-Ti at 4 h. Moreover, Ga-containing alloys showed good cytocompatibility with THP-1 macrophages at 24 h. In conclusion, it was demonstrated that Ga additions to Ti–45Nb are beneficial to corrosion resistance and showed promising initial host and bacterial interactions.

This paper attempts to analyse the technique of assimilation of classical Chinese writing into the Japanese literary tradition of the early medieval period. The author’s main focus is one of the three styles used by Japanese authors of the time, namely the mixed Japanese-Chinese style (the so-called wakan konkō buntai). It was used in various prose genres, including travel diaries. Referring to the text of Kaidōki (Records of [a journey along] the seacoast road), a Japanese travel account from the early 13th century, the author shows on the selected source material how, in accordance with Bakhtin’s understanding of heteroglossia, a dialogue occurs on the level of Chinese and Japanese writing and how intertextual relations can influence the formation of the style of a literary work. As can be noted, the historical and literary borrowings from the Chinese tradition (the rich Sino-Japanese vocabulary and the prosaised poems originally composed in classical Chinese) enriched the semantic layer of the Japanese text. This was also reflected in the style of the work, which, despite its “crabbedness” and the fact that it was shaped by the experience of borrowed but also native polyphony, seems to be the optimal way to express it.

We analyze the results of the test of π/2 qubit rotations on a public quantum computer provided by IBM. We measure a single qubit rotated by π/2 about a random axis, and we accumulate vast statistics of the results. The test performed on different devices shows systematic deviations from the theoretical predictions, which appear at level 10–3. Some of the differences, beyond 5 standard deviations, cannot be explained by simple corrections due to nonlinearities of pulse generations. The magnitude of the deviation is comparable with the randomized benchmarking of the gate, but we additionally observe a pronounced parametric dependence. We discuss other possible reasons for the deviations, including states beyond the single-qubit space. The deviations have a similar structure for various devices used at different times, so they can also serve as a diagnostic tool to eliminate imperfect gate implementations and a faithful description of the involved physical systems.

This study demonstrates that changes in mindfulness predict subsequent changes in well-being in a data set including individuals who recently engaged in psychedelic use.

Sirtuin 6 (SIRT6) is an NAD+-dependent histone H3 deacetylase that is prominently found associated with chromatin, attenuates transcriptionally active promoters and regulates DNA repair, metabolic homeostasis and lifespan. Unlike other sirtuins, it has low affinity to free histone tails but demonstrates strong binding to nucleosomes. It is poorly understood how SIRT6 docking on nucleosomes stimulates its histone deacetylation activity. Here, we present the structure of human SIRT6 bound to a nucleosome determined by cryogenic electron microscopy. The zinc finger domain of SIRT6 associates tightly with the acidic patch of the nucleosome through multiple arginine anchors. The Rossmann fold domain binds to the terminus of the looser DNA half of the nucleosome, detaching two turns of the DNA from the histone octamer and placing the NAD+ binding pocket close to the DNA exit site. This domain shows flexibility with respect to the fixed zinc finger and moves with, but also relative to, the unwrapped DNA terminus. We apply molecular dynamics simulations of the histone tails in the nucleosome to show that in this mode of interaction, the active site of SIRT6 is perfectly poised to catalyze deacetylation of the H3 histone tail and that the partial unwrapping of the DNA allows even lysines close to the H3 core to reach the enzyme.

BackgroundAlthough melanoma survival rates have improved in recent years, survivors remain at risk of recurrence, second primary cancers, and keratinocyte carcinomas. The National Comprehensive Cancer Network recommends skin examinations by a physician every 3 to 12 months. Regular thorough skin self-examinations (SSEs) are recommended for survivors of melanoma to promote the detection of earlier-stage, thinner melanomas, which are associated with improved survival and lower treatment costs. Despite their importance, less than a quarter of survivors of melanoma engage in SSEs. ObjectivePreviously, our team developed and evaluated a web-based, fully automated intervention called mySmartSkin (MSS) that successfully improved SSE among survivors of melanoma. Enhancements were proposed to improve engagement with and outcomes of MSS. The purpose of this paper is to describe the rationale and methodology for a type-1 hybrid effectiveness-implementation randomized trial evaluating the enhanced MSS versus control and exploring implementation outcomes and contextual factors. MethodsThis study will recruit from state cancer registries and social media 300 individuals diagnosed with cutaneous malignant melanoma between 3 months and 5 years after surgery who are currently cancer free. Participants will be randomly assigned to either enhanced MSS or a noninteractive educational web page. Surveys will be collected from both arms at baseline and at 3, 6, 12, and 18 months to assess measures of intervention engagement, barriers, self-efficacy, habit, and SSE. The primary outcome is thorough SSE. The secondary outcomes are the diagnosis of new or recurrent melanomas and sun protection practices. ResultsMultilevel modeling will be used to examine whether there are significant differences in survivor outcomes between MSS and the noninteractive web page over time. Mixed methods will evaluate reach, adoption, implementation (including costs), and potential for maintenance of MSS, as well as contextual factors relevant to those outcomes and future scale-up. ConclusionsThis trial has the potential to improve outcomes in survivors of melanoma. If MSS is effective, the results could guide its implementation in oncology care and nonprofit organizations focused on skin cancers. International Registered Report Identifier (IRRID)RR1-10.2196/52689

Mangrove forests are essential on the Amazon coast, as local communities widely use their wood. However, it is still necessary to understand the mechanical properties of wood typical of mangroves. Our main objective was to understand the influence of density on mechanical properties. Then, we tested the hypothesis that wood density has a stronger influence on the mechanical properties of R. mangle trees. Five trees of each dominant mangrove species were cut, and the mechanical properties of wood from these species were analyzed according to ASTM D143-14. Rhizophora mangle wood presented the highest average values compared to other mangrove species for mechanical properties (ρ12% = 1031.6 kg m-3; fv0 = 21.8 Mpa; fc0 = 79.6 Mpa; fM = 190.0 Mpa; EM0 = 18.8 Gpa), as well as for resistance and rigidity. Wood from mangrove trees on the Amazon coast has the same trend of mechanical properties as trees from Asian mangroves. Avicennia germinans and Laguncularia racemosa have a moderate rating. Rhizophora mangle stands out for presenting the highest values of these properties, with the species of Rhizophoraceae being considered the most resistant wood among mangrove species worldwide.