Search

BackgroundWhooping cough due to Bordetella pertussis (BP) and/or B. parapertussis (BPP) is a highly contagious infection sometimes fatal for infants. Africa accounts for the largest share of cases and deaths worldwide. To evaluate pertussis circulation, we conducted a hospital-based prospective study (PS) including household contact-cases investigation (CCS) and a sero-epidemiological cross-sectional study (SECS).MethodsThe PS, in which Bordetella diagnostics (qPCR) were performed, included infants aged ≤6 months presenting with ≥5 days of cough associated with one pertussis-like symptom. CCS was performed using qPCR and serology regardless of clinical signs. In the SECS, serology was performed in children aged 3-15 years with primary pertussis immunization.ResultsStudy took place in Abidjan between April 2019 and July 2021. In the PS, 187 infants with median age of 2.8 months were enrolled. A total of 42 (22.5%) were confirmed as positive, including 29 (15.5%), 4 (2.1%) and 9 (4.8%) of BP, BPP and BP/BPP coinfections respectively. Age ConclusionOur study highlighted high circulation of pertussis. Barriers to accessing boosters recommended by WHO need to be overcome. Laboratory capacities are key at individual level and to build an effective surveillance system.

ObjectiveFor leaders of small and medium-sized enterprises (SMEs) grappling with diverse tasks and stressors, personality functioning can play a key role on stress perception and building and managing professional relationships. We investigated the relationship between SME leaders' personality functioning on the dimensions of self-perception and self-regulation on perceived stress reactivity (PSR), and symptoms of anxiety and depression.MethodsA cross-sectional sub analysis of a multi-centre RCT project was performed. A sample of N = 174 SME leaders from various sectors in southern Germany were examined on their self-rated levels of personality functioning (OPD-SQ), involving self-perception (facets: self-reflection, affect differentiation, sense of identity) and self-reflection (facets: impulse control, affect tolerance, regulation of self-esteem), with higher scores indicating lower levels of personality functioning. The outcome variables were perceived stress reactivity (PSRS) and symptoms of depression and anxiety (HADS).ResultsThe mean score for symptoms of anxiety was M = 6.13 (SD = 3.34), depression M = 4.40 (SD = 3.35), and for PSRS M = 21.39 (SD = 8.04). The mean sum score for self-perception was M = 7.71 (SD = 7.19) and for self-regulation M = 10.50 (SD = 7.09). The results of three regression models showed that higher scores for affect differentiation (rsp = .13), impulse control (rsp = .14) and regulation of self-esteem (rsp = .29) were associated with higher scores for PSR. Higher scores for affect differentiation (rsp = .17) and affect tolerance (rsp = .20) were significantly associated with higher scores for anxiety. A higher score for regulation of self-esteem (rsp = .17) was associated with higher depression scores.ConclusionThis study highlights the association between core dimensions of SME leaders' personality functioning and mental distress. The findings can be applied on interventions and health promotion and the establishment of high-quality professional relationships and leadership skills.

BackgroundStereotactic radiosurgery (SRS) is an effective therapy for brain metastases. Response is assessed with serial 1H magnetic resonance imaging (MRI). Early markers for response are desirable to allow for individualized treatment adaption. Previous studies indicated that radiotherapy might have impact on tissue sodium concentration. Thus, 23Na MRI could provide early quantification of response to SRS.PurposeWe investigated whether longitudinal detection of tissue sodium concentration alteration within brain metastases and their peritumoral tissue after SRS with 23Na MRI was feasible.Study typeProspective.PopulationTwelve patients with a total of 14 brain metastases from various primary tumors.Assessment23Na MRI scans were acquired from patients 2 days before, 5 days after, and 40 days after SRS. Gross tumor volume (GTV) and healthy-appearing regions were manually segmented on the MPRAGE obtained 2 days before SRS, onto which all 23Na MR images were coregistered. Radiation isodose areas within the peritumoral tissue were calculated with the radiation planning system. Tissue sodium concentration before and after SRS within GTV, peritumoral tissue, and healthy-appearing regions as well as the routine follow-up with serial MRI were evaluated.Statistical testsResults were compared using Student's t-test and correlation was evaluated with Pearson's correlation coefficient.ResultsWe found a positive correlation between the tissue sodium concentration within the peritumoral tissue and radiation dosage. Two patients showed local progression and a differing tissue sodium concentration evolution within GTV and the peritumoral tissue compared to mean tissue sodium concentration of the other patients. No significant tissue sodium concentration changes were observed within healthy-appearing regions.ConclusionTissue sodium concentration assessment within brain metastases and peritumoral tissue after SRS with 23Na MRI is feasible and might be able to quantify tissue response to radiation.

Equid alphaherpesviruses 1 (EHV-1) and 4 (EHV-4) are closely related and both endemic in horses worldwide. Both viruses replicate in the upper respiratory tract, but EHV-1 may additionally lead to abortion and equine herpesvirus myeloencephalopathy (EHM). We focused on antibody responses in horses against the receptor-binding glycoprotein D of EHV-1 (gD1), which shares a 77% amino acid identity with its counterpart in EHV-4 (gD4). Both antigens give rise to cross-reacting antibodies, including neutralizing antibodies. However, immunity against EHV-4 is not considered protective against EHM. While a diagnostic ELISA to discriminate between EHV-1 and EHV-4 infections is available based on type-specific fragments of glycoprotein G (gG1 and gG4, respectively), the type-specific antibody reaction against gD1 has not yet been sufficiently addressed. Starting from the N-terminus of gD1, we developed luciferase immunoprecipitation system (LIPS) assays, using gD1-fragments of increasing size as antigens, i.e. gD1_83 (comprising the first 83 amino acids), gD1_160, gD1_180, and gD1_402 (the full-length molecule). These assays were then used to analyse panels of horse sera from Switzerland (n = 60) and Iceland (n = 50), the latter of which is considered EHV-1 free. We detected only one true negative horse serum from Iceland, whereas all other sera in both panels were seropositive for both gG4 (ELISA) and gD1 (LIPS against gD1_402). In contrast, seropositivity against gG1 was rather rare (35% Swiss sera; 14% Icelandic sera). Therefore, a high percentage of antibodies against gD1 could be attributed to cross-reaction and due to EHV-4 infections. In contrast, the gD1_83 fragment was able to identify sera with type-specific antibodies against gD1. Interestingly, those sera stemmed almost exclusively from vaccinated horses. Although it is uncertain that the N-terminal epitopes of gD1 addressed in this communication are linked to better protection, we suggest that in future vaccine developments, type-common antigens should be avoided, while a broad range of type-specific antigens should be favored.

Sampling of the North Sea trawl fishery for lesser sandeel (Ammodytes marinus) showed that 96% of the catch weight consisted of the target species, and experimental sea trials demonstrated that the observed small bycatch percentages of haddock (Melanogrammus aeglefinus), mackerel (Scomber scombrus) and grey gurnard (Eutrigla gurnardus) could be significantly lowered by inserting a netting-based sorting device, an Excluder, in front of the codend. The sandeel fishery is conducted with small meshes in the codend, due to the small size and elongated body shape of this species. It is not mandatory for sandeel trawls to have any other selection devices than the small-meshed codend, and this can potentially cause problems with bycatch of unwanted species, if these are abundant on the fishing grounds. Therefore, we sampled the catch composition in this fishery and further, we compared the capture efficiency and species composition of a standard trawl, and one fitted with an additional sorting device called the Excluder. Overall, results showed small percentages of bycatch in the trips sampled and during the trials, the excluder significantly reduced the bycatches of mackerel, grey gurnard, and haddock above certain sizes. For other bycatch species results were inconclusive due to wide confidence limits affected by low bycatch numbers during the trials. The overall capture efficiency for the target species was not affected by adding the excluder in the trawl except for a significant reduction for a few semi-centimetre groups of the largest sizes of the species. These results highlight the potential of the Excluder as a bycatch reduction tool in the sandeel fishery for situations where bycatch can constitute a problem.

IntroductionPostoperative complications affect up to 15% of surgical patients constituting a major part of the overall disease burden in a modern healthcare system. While several surgical risk calculators have been developed, none have so far been shown to decrease the associated mortality and morbidity. Combining deep neural networks and genomics with the already established clinical predictors may hold promise for improvement.MethodsThe UK Biobank was utilized to build linear and deep learning models for the prediction of surgery relevant outcomes. An initial GWAS for the relevant outcomes was initially conducted to select the Single Nucleotide Polymorphisms for inclusion in the models. Model performance was assessed with Receiver Operator Characteristics of the Area Under the Curve and optimum precision and recall. Feature importance was assessed with SHapley Additive exPlanations.ResultsModels were generated for atrial fibrillation, venous thromboembolism and pneumonia as genetics only, clinical features only and a combined model. For venous thromboembolism, the ROC-AUCs were 60.1% [59.6%-60.4%], 63.4% [63.2%-63.4%] and 66.6% [66.2%-66.9%] for the linear models and 51.5% [49.4%-53.4%], 63.2% [61.2%-65.0%] and 62.6% [60.7%-64.5%] for the deep learning SNP, clinical and combined models, respectively. For atrial fibrillation, the ROC-AUCs were 60.3% [60.0%-60.4%], 78.7% [78.7%-78.7%] and 80.0% [79.9%-80.0%] for the linear models and 59.4% [58.2%-60.9%], 78.8% [77.8%-79.8%] and 79.8% [78.8%-80.9%] for the deep learning SNP, clinical and combined models, respectively. For pneumonia, the ROC-AUCs were 50.1% [49.6%-50.6%], 69.2% [69.1%-69.2%] and 68.4% [68.0%-68.5%] for the linear models and 51.0% [49.7%-52.4%], 69.7% [.5%-70.8%] and 69.7% [68.6%-70.8%] for the deep learning SNP, clinical and combined models, respectively.ConclusionIn this report we presented linear and deep learning predictive models for surgery relevant outcomes. Overall, predictability was similar between linear and deep learning models and inclusion of genetics seemed to improve accuracy.

Stuttering is a speech disorder in which the flow of speech is disrupted by involuntary repetitions of sounds, syllables, words or phrases, stretched sounds or silent pauses in which the person is unable to produce sounds and sound transitions. Treatment success is the highest if stuttering is treated before the age of 6 years, before it develops into "persistent" stuttering. Stuttering treatment programs that focus directly on the speech of the child, like the Lidcombe Program, have shown to be effective in this age group. Mini-KIDS is also a treatment that focuses directly on the speech of the child. It is possible that capturing the increased brain plasticity at this age in combination with creating optimal conditions for recovery underlie these treatments' success rate. A treatment focusing on the cognitions, emotions and behaviour of the child, the social cognitive behaviour treatment (SCBT), is also frequently delivered in Belgium. In this study we want to compare, and collect data on the effectiveness, of these three treatment programs: Mini-KIDS, SCBT and the Lidcombe Program (protocol registered under number NCT05185726). 249 children will be allocated to one of three treatment groups. Stuttering specialists will treat the child (and guide the parents) with Mini-KIDS, the SCBT or the Lidcombe Program. They will be trained to deliver the programs meticulously. At 18 months after randomisation, the speech fluency of the child and the attitude of the child and parent(s) towards speech will be measured. It is expected that the three programs will achieve the same (near) zero levels of stuttering in nearly all children and a positive attitude towards speech at 18 months after the start of treatment. The amount of treatment hours to reach the (near) zero levels of stuttering will be compared between the different programmes. For families as well as for the health system this could generate important information.

The interaction between SARS-CoV-2 non-structural protein Nsp9 and the nanobody 2NSP90 was investigated by NMR spectroscopy using the paramagnetic perturbation methodology PENELOP (Paramagnetic Equilibrium vs Nonequilibrium magnetization Enhancement or LOss Perturbation). The Nsp9 monomer is an essential component of the replication and transcription complex (RTC) that reproduces the viral gRNA for subsequent propagation. Therefore preventing Nsp9 recruitment in RTC would represent an efficient antiviral strategy that could be applied to different coronaviruses, given the Nsp9 relative invariance. The NMR results were consistent with a previous characterization suggesting a 4:4 Nsp9-to-nanobody stoichiometry with the occurrence of two epitope pairs on each of the Nsp9 units that establish the inter-dimer contacts of Nsp9 tetramer. The oligomerization state of Nsp9 was also analyzed by molecular dynamics simulations and both dimers and tetramers resulted plausible. A different distribution of the mapped epitopes on the tetramer surface with respect to the former 4:4 complex could also be possible, as well as different stoichiometries of the Nsp9-nanobody assemblies such as the 2:2 stoichiometry suggested by the recent crystal structure of the Nsp9 complex with 2NSP23 (PDB ID: 8dqu), a nanobody exhibiting essentially the same affinity as 2NSP90. The experimental NMR evidence, however, ruled out the occurrence in liquid state of the relevant Nsp9 conformational change observed in the same crystal structure.

BackgroundDigital literacy refers to the capacity to critically assess digital content, use digital tools in professional settings, and operate digital devices with proficiency. The healthcare sector has rapidly digitized in the last few decades. This systematic review and meta-analysis aimed to assess the digital literacy level of health professionals in the Ethiopian health sector and identify associated factors. The study reviewed relevant literature and analyzed the data to provide a comprehensive understanding of the current state of digital literacy among health professionals in Ethiopia.MethodsThe study was examined by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Evidence was gathered from the databases of Google Scholar, Pub Med, Cochrane Library, Hinari, CINAHL, and Global Health. Consequently, five articles met the eligible criteria for inclusion. The analysis was carried out using STATA version 11. The heterogeneity was evaluated using the I2 test, while the funnel plot and Egger's regression test statistic were used to examine for potential publication bias. The pooled effect size of each trial is evaluated using a random effect model meta-analysis, which provides a 95% confidence interval.ResultA total of five articles were included in this meta-analysis and the overall pooled prevalence of this study was 49.85% (95% CI: 37.22-62.47). six variables, Monthly incomes AOR = 3.89 (95% CI: 1.03-14.66), computer literacy 2.93 (95% CI: 1.27-6.74), perceived usefulness 1.68 (95% CI: 1.59-4.52), educational status 2.56 (95% CI: 1.59-4.13), attitude 2.23 (95% CI: 1.49-3.35), perceived ease of use 2.22 (95% CI: 1.52-3.23) were significantly associated with the outcome variable.ConclusionThe findings of the study revealed that the overall digital literacy level among health professionals in Ethiopia was relatively low. The study highlights the importance of addressing the digital literacy gap among health professionals in Ethiopia. It suggests the need for targeted interventions, such as increasing monthly incomes, giving computer training, creating a positive attitude, and educational initiatives, to enhance digital literacy skills among health professionals. By improving digital literacy, health professionals can effectively utilize digital technologies and contribute to the advancement of healthcare services in Ethiopia.

This study aimed to evaluate the seroprevalence and spatial and temporal clustering of SARS-CoV-2 antibodies in household cats within 63 counties in Illinois from October 2021 to May 2023. The analysis followed a stepwise approach. First, in a choropleth point map, we illustrated the distribution of county-level seroprevalence of SARS-CoV-2 antibodies. Next, spatial interpolation was used to predict the seroprevalence in counties without recorded data. Global and local clustering methods were used to identify the extent of clustering and the counties with high or low seroprevalence, respectively. Next, temporal, spatial, and space-time scan statistic was used to identify periods and counties with higher-than-expected seroprevalence. In the last step, to identify more distinct areas in counties with high seroprevalence, city-level analysis was conducted to identify temporal and space-time clusters. Among 1,715 samples tested by serological assays, 244 samples (14%) tested positive. Young cats had higher seropositivity than older cats, and the third quarter of the year had the highest odds of seropositivity. Three county-level space-time clusters with higher-than-expected seroprevalence were identified in the northeastern, central-east, and southwest regions of Illinois, occurring between June and October 2022. In the city-level analysis, 2 space-time clusters were identified in Chicago's downtown and the southwestern suburbs of Chicago between June and September 2022. Our results suggest that the high density of humans and cats in large cities such as Chicago, might play a role in the transmission and clustering of SARS-CoV-2. Our study provides an in-depth analysis of SARS-CoV-2 epidemiology in Illinois household cats, which will aid in COVID-19 control and prevention.

IntroductionOne of the targets for the third sustainable development goals is to reduce worldwide maternal mortality ratio (MMR) to less than 70 deaths per 100,000 live births by 2030. To address issues affecting women and the newborns during childbirth and postnatal period, concerted efforts from governments and their stakeholders are crucial to maximize the use of technology to enhance frontline health professionals' skills to provide the emergency obstetric and newborn care (EmONC). However, no study has garnered nurses' and midwives' perspectives regarding the application of technology-enhanced learning approach to provide on-the-job Continuous Professional Development (CPD) and factors that may influence the application of this training approach in the Rwandan context.MethodsThe study collected data from nurses and midwives from forty (40) public health facilities in remote areas nationwide. The study applied a qualitative descriptive design to explore and describe nurses' and midwives' perspectives on the feasibility and acceptability of technology enhanced learning approaches such as e-learning, phone-based remote training, and other online methods to provide trainings in EmONC. Two focus group discussions with EmONC mentors, two with nurses and midwives were conducted. Twelve key informant interviews were conducted. Participants were selected purposively. In total, 54 individuals were included in this study. A thematic approach was used to analyse data.ResultsNurses and midwives highlighted the need to provide refresher trainings about the management of pre-eclampsia. Most of the EmONC trainings are still provided face-to-face and the use of technology enhanced learning approaches have not yet been embraced in delivering EmONC CPDs for nurses and midwives in remote areas. Nurses and midwives found the first developed prototype of smartphone app training of the EmONC acceptable as it met the midwives' expectations in terms of the knowledge and skills' gap in EmONC.ConclusionAlthough the newly developed application was found acceptable, further research involving practical sessions by nurses and midwives using the developed application is needed to garner views about the ease of use of the application, relevance of the EmONC uploaded content on the app, and needed improvements on the app to address their needs in EmONC.

[This corrects the article DOI: 10.1371/journal.pone.0282308.].

Integrating the voices of service users and providers in the design and delivery of health services increases the acceptability, relevance, and effectiveness of services. Such efforts are particularly important for youth opioid use treatments and services, which have failed to consider the unique needs of youth and families. Applying community-based participatory research (CBPR) and co-design can facilitate this process by contextualizing service user experiences at individual and community levels and supporting the collaborative design of innovative solutions for improving care. However, few studies demonstrate how to effectively integrate these methods and engage underserved populations in co-design. As such, this manuscript describes how our team wove CBPR and co-design methods to develop solutions for improving youth opioid use treatments and services in Canada. As per CBPR methods, national, provincial, and community partnerships were established to inform and support the project's activities. These partnerships were integral for recruiting service users (i.e., youth and caregivers) and service providers to co-design prototypes and support local testing and implementation. Co-design methods enabled understanding of the needs and experiences of youth, caregivers, and service providers, resulting in meaningful community-specific innovations. We used several engagement methods during the co-design process, including regular working group meetings, small group discussions, individual interviews and consultations, and feedback grids. Challenges involved the time commitment and resources needed for co-design, which were exacerbated by the COVID-19 pandemic and limited our ability to engage a diverse sample of youth and caregivers in the process. Strengths of the study included youth and caregiver involvement in the co-design process, which centered around their lived experiences; the therapeutic aspect of the process for participants; and the development of innovations that were accepted by design partners.

IntroductionMonthly intravenous infusion of broadly neutralizing monoclonal antibodies may be an attractive alternative to daily oral antiretroviral treatment for children living with HIV. However, acceptability among caregivers remains unknown.MethodsWe evaluated monthly infusion of dual bNAbs (VRCO1LS and 10-1074) as a treatment alternative to ART among children participating in the Tatelo Study in Botswana. Eligible children aged 2-5 years received 8-32 weeks of bNAbs overlapping with ART, and up to 24 weeks of bNAbs alone as monthly intravenous infusion. Using closed-ended questionnaires, we evaluated caregiver acceptability of each treatment strategy prior to the first bNAb administration visit (pre-intervention) and after the completion of the final bNAb administration visit (post-intervention).ResultsTwenty-five children completed the intervention phase of the study, and acceptability data were available from 24 caregivers at both time points. Responses were provided by the child's mother at both visits (60%), an extended family member at both visits (28%), or a combination of mother and an extended family member (12%). Caregiver acceptance of monthly bNAb infusions was extremely high both pre-and post-intervention, with 21/24 (87.5%) preferring bNAbs to ART pre-intervention, and 21/25 (84%) preferring bNAbs post-intervention. While no caregiver preferred ART pre-intervention, 2/25 preferred it post-intervention. Pre-intervention, 3 (13%) caregivers had no preference between monthly bNAbs or daily ART, and 2 (8%) had no preference post-intervention. Pre-intervention, the most common reasons for preferring bNAbs over ART were the perception that bNAbs were better at suppressing the virus than ART (n = 10) and the fact that infusions were dosed once monthly compared to daily ART (n = 9). Post-intervention, no dominant reason for preferring bNAbs over ART emerged from caregivers.ConclusionsMonthly intravenous bNAb infusions were highly acceptable to caregivers of children with HIV in Botswana and preferred over standard ART by the majority of caregivers.Clinical trial numberNCT03707977.

We investigated the social, emotional, and cognitive predictors of adherence to four health behaviors (handwashing, mask wearing, social contact limitations, and physical distancing) during one critical phase of the COVID-19 pandemic. We collected data (N = 5803, mean age = 53; 57% women) in Belgium at five time points between April and July 2021, a time during which infections evolved from high (third wave of the pandemic) to low numbers of COVID-19 cases. The results show that the social, emotional, and cognitive predictors achieved high levels of explained variance (R2 > .60). In particular, the central components of behavioral change (attitudes, intentions, control, habits, norms, and risk) were the strongest and most consistent predictors of health behaviors over time. Likewise, autonomous motivation and empathetic emotions (e.g., attentive, compassionate) had a positive impact on health behavior adherence, whereas it was the opposite for lively emotions (e.g., active, enthusiastic). These results offer policymakers actionable insights into the most potent and stable factors associated with health behaviors, equipping them with effective strategies to curtail the spread of future infectious diseases.

Previous research shows that stereotypes can distort the visual representation of groups in a top-down fashion. In the present endeavor, we tested if the compensation effect-the negative relationship that emerges between the social dimensions of warmth and competence when judging two social targets-would bias the visual representations of these targets in a compensatory way. We captured participants' near spontaneous facial prototypes of social targets by means of an unconstrained technique, namely the reverse correlation. We relied on a large multi-phase study (N = 869) and found that the expectations of the facial content of two novel groups that differed on one of the two social dimensions are biased in a compensatory manner on the facial dimensions of trustworthiness, warmth, and dominance but not competence. The present research opens new avenues by showing that compensation not only manifests itself on abstract ratings but that it also orients the visual representations of social targets.

Drought and heat are two stresses that often occur together and may pose significant risks to crops in future climates. However, the combined effects of these two stressors have received less attention than single-stressor investigations. This study used a rapid and straightforward phenotyping method to quantify the variation in 128 African eggplant genotype responses to drought, heat, and the combined effects of heat and drought at the seedling stage. The study found that the morphophysiological traits varied significantly among the 128 eggplants, highlighting variation in response to abiotic stresses. Broad-sense heritability was high (> 0.60) for chlorophyll content, plant biomass and performance index, electrolyte leakage, and total leaf area. Positive and significant relationships existed between biomass and photosynthetic parameters, but a negative association existed between electrolyte leakage and morpho-physiological traits. The plants underwent more significant stress when drought and heat stress were imposed concurrently than under single stresses, with the impact of drought on the plants being more detrimental than heat. There were antagonistic effects on the morphophysiology of the eggplants when heat and drought stress were applied together. Resilient genotypes such as RV100503, RV100501, JAMBA, LOC3, RV100164, RV100169, LOC 3, RV100483, GH5155, RV100430, GH1087, GH1087*, RV100388, RV100387, RV100391 maintained high relative water content, low electrolyte leakage, high Fv/Fm ratio and performance index, and increased biomass production under abiotic stress conditions. The antagonistic interactions between heat and drought observed here may be retained or enhanced during several stress combinations typical of plants' environments and must be factored into efforts to develop climate change-resilient crops. This paper demonstrates improvised climate chambers for high throughput, reliable, rapid, and cost-effective screening for heat and drought and combined stress tolerance in plants.

Linear regression of optical coherence tomography measurements of peripapillary retinal nerve fiber layer thickness is often used to detect glaucoma progression and forecast future disease course. However, current measurement frequencies suggest that clinicians often apply linear regression to a relatively small number of measurements (e.g., less than a handful). In this study, we estimate the accuracy of linear regression in predicting the next reliable measurement of average retinal nerve fiber layer thickness using Zeiss Cirrus optical coherence tomography measurements of average retinal nerve fiber layer thickness from a sample of 6,471 eyes with glaucoma or glaucoma-suspect status. Linear regression is compared to two null models: no glaucoma worsening, and worsening due to aging. Linear regression on the first M ≥ 2 measurements was significantly worse at predicting a reliable M+1st measurement for 2 ≤ M ≤ 6. This range was reduced to 2 ≤ M ≤ 5 when retinal nerve fiber layer thickness measurements were first "corrected" for scan quality. Simulations based on measurement frequencies in our sample-on average 393 ± 190 days between consecutive measurements-show that linear regression outperforms both null models when M ≥ 5 and the goal is to forecast moderate (75th percentile) worsening, and when M ≥ 3 for rapid (90th percentile) worsening. If linear regression is used to assess disease trajectory with a small number of measurements over short time periods (e.g., 1-2 years), as is often the case in clinical practice, the number of optical coherence tomography examinations needs to be increased.

Background: Chronic hepatitis B virus (HBV) infection is still a major public health problem. In response to the World Health Organization (WHO), Tanzania implemented immunization and treatment to achieve the eradication of HBV infection by 2030. To achieve this goal, frequent updates of demographic data, antiviral therapy eligibility, and uptake are essential. We therefore evaluated demographic data, antiviral therapy eligibility, and uptake among chronically HBV-infected patients attending at Bugando Medical Centre (BMC), Tanzania. Methods: A cross-sectional study enrolled 196 chronic HBV patients from April 23, 2023, to October 10, 2023, at BMC, where 100 and 96 patients were retrospectively and prospectively enrolled, respectively. Study's ethical clearance and permission were observed by the Catholic University of Health and Allied Sciences/Bugando Medical Centre research ethics and review committee and the Bugando Medical Centre management respectively. For all patients, socio-demographic data and whole blood samples were obtained. Full blood picture, alanine and aspartate amino transferases, and HBV viral load parameters were determined. Aspartate-Platelet Ratio Index (APRI) and Fibrosis Four (FIB-4) scores were calculated according to their respective formulas. Therapy eligibility and uptake were evaluated according to the 2015 WHO HBV prevention, treatment, and care guidelines. The data were summarized and analysed using STATA version 15. Results: The median age for all patients was 39 [IQR: 32–47.5] years. Nearly all study patients, 99% (194/196), were older than 20 years old, with significant male dominance (73.5% [144/196] versus 26.5% [52/196]; p<0.0001). Anti-HBV antiviral therapy eligibility was 22.4%, while uptake was 6.8% (3/4), which was significantly lower than the WHO expectation of 80% (p <0.0001). Conclusion: Almost all chronically HBV-infected patients attending at BMC were older than 20 years old and were significantly dominated by males. Antiviral therapy uptake was remarkably lower than expected by the WHO towards combating HBV infection by 2030. [ABSTRACT FROM AUTHOR]

BackgroundGenome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome.Methods and resultsUsing samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event.ConclusionThis study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.

Throughout the humid tropics, increased land disturbance and concomitant road construction increases erosion and sediment delivery to rivers. Building road networks in developing countries is commonly a priority for international development funding based on anticipated socio-economic benefits. Yet the resulting erosion from roads, which recent studies have shown result in at least ten-fold increases in erosion rates, is not fully accounted for. While effects of road-derived sediment on aquatic ecosystems have been documented in temperate climates, little has been published on the effects of road-induced sediment on aquatic ecosystems in developing countries of the tropics. We studied periphyton biomass and macroinvertebrate communities on the deltas of Río San Juan tributaries, comparing north-bank tributaries draining undisturbed rain forest with south-bank tributaries receiving runoff from a partially-built road experiencing rapid erosion. Periphyton biomass, richness and abundance of macroinvertebrates overall, and richness and abundance of Ephemeroptera, Plecoptera and Trichoptera were higher on the north-bank tributary deltas than the south-bank tributary deltas. These findings were consistent with prior studies in temperate climates showing detrimental effects of road-derived fine sediment on aquatic organisms. A Non-Metric Multidimensional Scaling (NMDS) analysis showed the impacted community on the south-bank deltas was influenced by poorly-sorted substrate with greater proportions of fine sediment and higher water temperatures.

BackgroundFibrinogen is an essential hemostatic factor and cardiovascular disease risk factor. Early attempts at evaluating the causal effect of fibrinogen on coronary heart disease (CHD) and myocardial infraction (MI) using Mendelian randomization (MR) used single variant approaches, and did not take advantage of recent genome-wide association studies (GWAS) or multi-variant, pleiotropy robust MR methodologies.Methods and findingsWe evaluated evidence for a causal effect of fibrinogen on both CHD and MI using MR. We used both an allele score approach and pleiotropy robust MR models. The allele score was composed of 38 fibrinogen-associated variants from recent GWAS. Initial analyses using the allele score used a meta-analysis of 11 European-ancestry prospective cohorts, free of CHD and MI at baseline, to examine incidence CHD and MI. We also applied 2 sample MR methods with data from a prevalent CHD and MI GWAS. Results are given in terms of the hazard ratio (HR) or odds ratio (OR), depending on the study design, and associated 95% confidence interval (CI). In single variant analyses no causal effect of fibrinogen on CHD or MI was observed. In multi-variant analyses using incidence CHD cases and the allele score approach, the estimated causal effect (HR) of a 1 g/L higher fibrinogen concentration was 1.62 (CI = 1.12, 2.36) when using incident cases and the allele score approach. In 2 sample MR analyses that accounted for pleiotropy, the causal estimate (OR) was reduced to 1.18 (CI = 0.98, 1.42) and 1.09 (CI = 0.89, 1.33) in the 2 most precise (smallest CI) models, out of 4 models evaluated. In the 2 sample MR analyses for MI, there was only very weak evidence of a causal effect in only 1 out of 4 models.ConclusionsA small causal effect of fibrinogen on CHD is observed using multi-variant MR approaches which account for pleiotropy, but not single variant MR approaches. Taken together, results indicate that even with large sample sizes and multi-variant approaches MR analyses still cannot exclude the null when estimating the causal effect of fibrinogen on CHD, but that any potential causal effect is likely to be much smaller than observed in epidemiological studies.

Objective: For leaders of small and medium-sized enterprises (SMEs) grappling with diverse tasks and stressors, personality functioning can play a key role on stress perception and building and managing professional relationships. We investigated the relationship between SME leaders' personality functioning on the dimensions of self-perception and self-regulation on perceived stress reactivity (PSR), and symptoms of anxiety and depression. Methods: A cross-sectional sub analysis of a multi-centre RCT project was performed. A sample of N = 174 SME leaders from various sectors in southern Germany were examined on their self-rated levels of personality functioning (OPD-SQ), involving self-perception (facets: self-reflection, affect differentiation, sense of identity) and self-reflection (facets: impulse control, affect tolerance, regulation of self-esteem), with higher scores indicating lower levels of personality functioning. The outcome variables were perceived stress reactivity (PSRS) and symptoms of depression and anxiety (HADS). Results: The mean score for symptoms of anxiety was M = 6.13 (SD = 3.34), depression M = 4.40 (SD = 3.35), and for PSRS M = 21.39 (SD = 8.04). The mean sum score for self-perception was M = 7.71 (SD = 7.19) and for self-regulation M = 10.50 (SD = 7.09). The results of three regression models showed that higher scores for affect differentiation (rsp =.13), impulse control (rsp =.14) and regulation of self-esteem (rsp =.29) were associated with higher scores for PSR. Higher scores for affect differentiation (rsp =.17) and affect tolerance (rsp =.20) were significantly associated with higher scores for anxiety. A higher score for regulation of self-esteem (rsp =.17) was associated with higher depression scores. Conclusion: This study highlights the association between core dimensions of SME leaders' personality functioning and mental distress. The findings can be applied on interventions and health promotion and the establishment of high-quality professional relationships and leadership skills. [ABSTRACT FROM AUTHOR]

Background: Whooping cough due to Bordetella pertussis (BP) and/or B. parapertussis (BPP) is a highly contagious infection sometimes fatal for infants. Africa accounts for the largest share of cases and deaths worldwide. To evaluate pertussis circulation, we conducted a hospital-based prospective study (PS) including household contact-cases investigation (CCS) and a sero-epidemiological cross-sectional study (SECS). Methods: The PS, in which Bordetella diagnostics (qPCR) were performed, included infants aged ≤6 months presenting with ≥5 days of cough associated with one pertussis-like symptom. CCS was performed using qPCR and serology regardless of clinical signs. In the SECS, serology was performed in children aged 3–15 years with primary pertussis immunization. Results: Study took place in Abidjan between April 2019 and July 2021. In the PS, 187 infants with median age of 2.8 months were enrolled. A total of 42 (22.5%) were confirmed as positive, including 29 (15.5%), 4 (2.1%) and 9 (4.8%) of BP, BPP and BP/BPP coinfections respectively. Age <3 months, low BMI, apnea and inclusion period were identified as risk factors of infection. In the CCIS, 36 households were investigated, representing 158 people with median age of 21.4 years. BP and/or BPP infection was confirmed for 77/157 (49.0%). Twenty-nine households (81%) had at least one positive case. Sixty-seven (42.7%) contact cases were categorized as possibly contaminated, mainly siblings older than five years (25.4%). Twenty-seven contact cases were considered as possible contaminators, primarily mothers (26%). In the SECS, 444 people were enrolled. Two hundred and thirty-eight (53.6%) and nine (2.0%) children had received one and two boosters, respectively. A positive serology was observed in 96 (21.7%) of children and adolescents. Conclusion: Our study highlighted high circulation of pertussis. Barriers to accessing boosters recommended by WHO need to be overcome. Laboratory capacities are key at individual level and to build an effective surveillance system. [ABSTRACT FROM AUTHOR]

Background: Stereotactic radiosurgery (SRS) is an effective therapy for brain metastases. Response is assessed with serial 1H magnetic resonance imaging (MRI). Early markers for response are desirable to allow for individualized treatment adaption. Previous studies indicated that radiotherapy might have impact on tissue sodium concentration. Thus, 23Na MRI could provide early quantification of response to SRS. Purpose: We investigated whether longitudinal detection of tissue sodium concentration alteration within brain metastases and their peritumoral tissue after SRS with 23Na MRI was feasible. Study type: Prospective. Population: Twelve patients with a total of 14 brain metastases from various primary tumors. Assessment: 23Na MRI scans were acquired from patients 2 days before, 5 days after, and 40 days after SRS. Gross tumor volume (GTV) and healthy-appearing regions were manually segmented on the MPRAGE obtained 2 days before SRS, onto which all 23Na MR images were coregistered. Radiation isodose areas within the peritumoral tissue were calculated with the radiation planning system. Tissue sodium concentration before and after SRS within GTV, peritumoral tissue, and healthy-appearing regions as well as the routine follow-up with serial MRI were evaluated. Statistical tests: Results were compared using Student's t-test and correlation was evaluated with Pearson's correlation coefficient. Results: We found a positive correlation between the tissue sodium concentration within the peritumoral tissue and radiation dosage. Two patients showed local progression and a differing tissue sodium concentration evolution within GTV and the peritumoral tissue compared to mean tissue sodium concentration of the other patients. No significant tissue sodium concentration changes were observed within healthy-appearing regions. Conclusion: Tissue sodium concentration assessment within brain metastases and peritumoral tissue after SRS with 23Na MRI is feasible and might be able to quantify tissue response to radiation. [ABSTRACT FROM AUTHOR]

Background: Associations between intraoperative hypotension (IOH) and various postoperative outcomes were shown in retrospective trials using a variety of different definitions of IOH. This complicates the comparability of these trials and makes clinical application difficult. Information about the best performing definitions of IOH regarding 30-day mortality, hospital length of stay (hLOS), and postanesthesia care unit length of stay (PACU-LOS) is missing. Methods: A retrospective cohort trial was conducted using data from patients undergoing noncardiothoracic surgery. We split the obtained dataset into two subsets. First, we used one subset to choose the best fitting definitions of IOH for the outcomes 30-day mortality, hLOS, and PACU-LOS. The other subset was used to independently assess the performance of the chosen definitions of IOH. Results: The final cohort consisted of 65,454 patients. In the shaping subset, nearly all tested definitions of IOH showed associations with the three outcomes, where the risk of adverse outcomes often increased continuously with decreasing MAP. The best fitting definitions were relative time with a MAP (mean arterial pressure) of <80 mmHg for 30-day mortality, lowest MAP for one minute for hLOS, and lowest MAP for one cumulative minute for PACU-LOS. Testing these three definitions of IOH in the independent second subset confirmed the associations of IOH with 30-day mortality, hLOS, and PACU-LOS. Conclusions: Using a data-driven approach, we identified the best fitting definitions of IOH for 30-day mortality, hLOS, and PACU-LOS. Our results demonstrate the need for careful selection of IOH definitions. Clinical trial number: n/a, EC #2245/2020 [ABSTRACT FROM AUTHOR]

The European Quality In Preclinical Data (EQIPD) consortium was born from the fact that publications report challenges with the robustness, rigor, and/or validity of research data, which may impact decisions about whether to proceed with further preclinical testing or to advance to clinical testing, as well as draw conclusions on the predictability of preclinical models. To address this, a consortium including multiple research laboratories from academia and industry participated in a series of electroencephalography (EEG) experiments in mice aimed to detect sources of variance and to gauge how protocol harmonisation and data analytics impact such variance. Ultimately, the goal of this first ever between-laboratory comparison of EEG recordings and analyses was to validate the principles that supposedly increase data quality, robustness, and comparability. Experiments consisted of a Localisation phase, which aimed to identify the factors that influence between-laboratory variability, a Harmonisation phase to evaluate whether harmonisation of standardized protocols and centralised processing and data analysis reduced variance, and a Ring-Testing phase to verify the ability of the harmonised protocol to generate consistent findings. Indeed, between-laboratory variability reduced from Localisation to Harmonisation and this reduction remained during the Ring-Testing phase. Results obtained in this multicentre preclinical qEEG study also confirmed the complex nature of EEG experiments starting from the surgery and data collection through data pre-processing to data analysis that ultimately influenced the results and contributed to variance in findings across laboratories. Overall, harmonisation of protocols and centralized data analysis were crucial in reducing laboratory-to-laboratory variability. To this end, it is recommended that standardized guidelines be updated and followed for collection and analysis of preclinical EEG data. [ABSTRACT FROM AUTHOR]

BackgroundReliably capturing sub-millimeter vessel wall motion over time, using dynamic Computed Tomography Angiography (4D CTA), might provide insight in biomechanical properties of these vessels. This may improve diagnosis, prognosis, and treatment decision making in vascular pathologies.PurposeThe aim of this study is to determine the most suitable image reconstruction method for 4D CTA to accurately assess harmonic diameter changes of vessels.MethodsAn elastic tube (inner diameter 6 mm, wall thickness 2 mm) was exposed to sinusoidal pressure waves with a frequency of 70 beats-per-minute. Five flow amplitudes were set, resulting in increasing sinusoidal diameter changes of the elastic tube, measured during three simulated pulsation cycles, using ECG-gated 4D CTA on a 320-detector row CT system. Tomographic images were reconstructed using one of the following three reconstruction methods: hybrid iterative (Hybrid-IR), model-based iterative (MBIR) and deep-learning based (DLR) reconstruction. The three reconstruction methods where based on 180 degrees (half reconstruction mode) and 360 degrees (full reconstruction mode) raw data. The diameter change, captured by 4D CTA, was computed based on image registration. As a reference metric for diameter change measurement, a 9 MHz linear ultrasound transducer was used. The sum of relative absolute differences (SRAD) between the ultrasound and 4D CTA measurements was calculated for each reconstruction method. The standard deviation was computed across the three pulsation cycles.ResultsMBIR and DLR resulted in a decreased SRAD and standard deviation compared to Hybrid-IR. Full reconstruction mode resulted in a decreased SRAD and standard deviations, compared to half reconstruction mode.Conclusions4D CTA can capture a diameter change pattern comparable to the pattern captured by US. DLR and MBIR algorithms show more accurate results than Hybrid-IR. Reconstruction with DLR is >3 times faster, compared to reconstruction with MBIR. Full reconstruction mode is more accurate than half reconstruction mode.

Telomerase reverse transcriptase (TERT) promoter mutations occur frequently in cancer, have been associated with increased TERT expression and cell proliferation, and could potentially influence therapeutic regimens for melanoma. As the role of TERT expression in malignant melanoma and the non-canonical functions of TERT remain understudied, we aimed to extend the current knowledge on the impact of TERT promoter mutations and expression alterations in tumor progression by analyzing several highly annotated melanoma cohorts. Using multivariate models, we found no consistent association for TERT promoter mutations or TERT expression with the survival rate in melanoma cohorts under immune checkpoint inhibition. However, the presence of CD4+ T cells increased with TERT expression and correlated with the expression of exhaustion markers. While the frequency of promoter mutations did not change with Breslow thickness, TERT expression was increased in metastases arising from thinner primaries. As single-cell RNA-sequencing (RNA-seq) showed that TERT expression was associated with genes involved in cell migration and dynamics of the extracellular matrix, this suggests a role of TERT during invasion and metastasis. Co-regulated genes found in several bulk tumors and single-cell RNA-seq cohorts also indicated non-canonical functions of TERT related to mitochondrial DNA stability and nuclear DNA repair. This pattern was also evident in glioblastoma and across other entities. Hence, our study adds to the role of TERT expression in cancer metastasis and potentially also immune resistance.

IntroductionAppropriate management of malaria demands early health seeking behaviour upon suspicion of malaria-like symptoms. This study examined malaria treatment seeking behaviour and associated factors among international students at University of Ghana.MethodsThe study used a cross-sectional and quantitative approach. Data collection was undertaken using a structured questionnaire administered on a random sample of 264 international students. Data obtained on malaria treatment and factors influencing treatment behaviors were analyzed using IBM, SPSS Statistics version 22. Associations between individual characteristics and Malaria treatment seeking behavior was assessed by Pearson Chi-square(X2) test of independence. Binary logistic regression model was built using a backwards Wald approach, with variables retained at Wald p-value ResultsThe findings show that 35% of the respondents obtained self-prescribed antimalarial at their utmost first choice of Malaria treatment. At bivariate level, a significant relationship between Malaria health-care seeking behaviour and:- Respondents continent, X2(1, N = 264) = 7.936, p = .005; Service accessibility, X2(1, N = 264) = 7.624, p = .006; Wait time, X2(1, N = 264) = 22.514, p ConclusionThere were widespread inappropriate health-care seeking behavior for Malaria treatment among international students. Improving accessibility to malaria treatment services, reducing wait time at health facilities and the treatment cost will address inappropriate malaria treatment health seeking behaviours among the international students.

BackgroundQuarantine is one of the most effective interventions to contain an infectious disease outbreak, yet it is one of the most disruptive. We investigated the quarantine of an entire village to better understand risk communication requirements for groups.MethodsWe conducted a cross-sectional, mixed-methods survey study on a single cohort of adult residents in Neustadt am Rennsteig, Germany, six weeks after the removal of a 14-day mandatory community quarantine. The survey response rate was 33% (289/883 residents).FindingsSurvey participants reported a lack of information on the quarantine implementation process. What authorities communicated was not necessarily what residents desired to know. While inhabitants used social media and telephones to communicate with each other, the official information sources were regional radio, television, newspapers and official websites. Public health authorities did not employ social media communication to engage with their communities. Despite a lack of information, the majority of respondents stated that they had complied with the quarantine and they expressed little sympathy for those who violated the quarantine. After lifting the quarantine, many respondents continued to avoid places where they suspected a significant risk of infection, such as family and friends' homes, doctor's offices and grocery stores.InterpretationThe survey participants utilised existing social networks to disseminate vital information and stabilise its group identity and behaviour (quarantine compliance). The authorities communicated sparsely in a unidirectional, top-down manner, without engaging the community. Despite the lack of official information, the social coherency of the group contributed to considerate and compliant conduct, but participants expressed dissatisfaction with official leadership and asked for more attention.ConclusionPublic health risk communication must engage with communities more effectively. This necessitates a deeper comprehension of groups, their modes of communication and their social needs.

ObjectivesClinical, time-dependent, therapeutic and diagnostic data of patients with LUTS are highly complex. To better manage these data for therapists' and researchers' we developed the application ShinyLUTS.Material and methodsThe statistical programming language R and the framework Shiny were used to develop a platform for data entry, monitoring of therapy and scientific data analysis. As part of a use case, ShinyLUTS was evaluated for patients with non-neurogenic LUTS who were receiving Rezum™ therapy.ResultsThe final database on patients with LUTS comprised a total of 8.118 time-dependent parameters in 11 data tables. Data entry, monitoring of therapy as well as data retrieval for scientific use, was deemed feasible, intuitive and well accepted.ConclusionThe ShinyLUTs application presented here is suitable for collecting, archiving, and managing complex data on patients with LUTS. Aside from the implementation in a scientific workflow, it is suited for monitoring treatment of patients and functional results over time.

The beta-adrenergic system is a potent stimulus for enhancing cardiac output that may become deleterious when energy metabolism is compromised as in heart failure. We thus examined whether the AMP-activated protein kinase (AMPK) that is activated in response to energy depletion may control the beta-adrenergic pathway. We studied the cardiac response to beta-adrenergic stimulation of AMPKα2-/- mice or to pharmacological AMPK activation on contractile function, calcium current, cAMP content and expression of adenylyl cyclase 5 (AC5), a rate limiting step of the beta-adrenergic pathway. In AMPKα2-/- mice the expression of AC5 (+50%), the dose response curve of left ventricular developed pressure to isoprenaline (p

FAM3C/ILEI is an important factor in epithelial-to-mesenchymal transition (EMT) induction, tumor progression and metastasis. Overexpressed in many cancers, elevated ILEI levels and secretion correlate with poor patient survival. Although ILEI's causative role in invasive tumor growth and metastasis has been demonstrated in several cellular tumor models, there are no available transgenic mice to study these effects in the context of a complex organism. Here, we describe the generation and initial characterization of a Tet-ON inducible Fam3c/ILEI transgenic mouse strain. We find that ubiquitous induction of ILEI overexpression (R26-ILEIind) at weaning age leads to a shortened lifespan, reduced body weight and microcytic hypochromic anemia. The anemia was reversible at a young age within a week upon withdrawal of ILEI induction. Vav1-driven overexpression of the ILEIind transgene in all hematopoietic cells (Vav-ILEIind) did not render mice anemic or lower overall fitness, demonstrating that no intrinsic mechanisms of erythroid development were dysregulated by ILEI and that hematopoietic ILEI hyperfunction did not contribute to death. Reduced serum iron levels of R26-ILEIind mice were indicative for a malfunction in iron uptake or homeostasis. Accordingly, the liver, the main organ of iron metabolism, was severely affected in moribund ILEI overexpressing mice: increased alanine transaminase and aspartate aminotransferase levels indicated liver dysfunction, the liver was reduced in size, showed increased apoptosis, reduced cellular iron content, and had a fibrotic phenotype. These data indicate that high ILEI expression in the liver might reduce hepatoprotection and induce liver fibrosis, which leads to liver dysfunction, disturbed iron metabolism and eventually to death. Overall, we show here that the novel Tet-ON inducible Fam3c/ILEI transgenic mouse strain allows tissue specific timely controlled overexpression of ILEI and thus, will serve as a versatile tool to model the effect of elevated ILEI expression in diverse tissue entities and disease conditions, including cancer.

When we engage in internally directed cognition, like doing mental arithmetic or mind wandering, fewer cognitive resources are assigned for other activities like reacting to perceptual input-an effect termed perceptual decoupling. However, the exact conditions under which perceptual decoupling occurs and its underlying cognitive mechanisms are still unclear. Hence, the present study systematically manipulated the task type (arithmetic, visuospatial) and workload (control, low, high) of the internal task in a within-subject design and tested its effects on voluntary saccades in a target-distractor saccade task. As expected, engagement in internal tasks delayed saccades to the target. This effect was moderated by time, task, and workload: The delay was largest right after internal task onset and then decreased, potentially reflecting the intensity of internal task demands. Saccades were also more delayed for the high compared to the low workload condition in the arithmetic task, whereas workload conditions had similarly high effects in the visuospatial task. Findings suggests that perceptual decoupling of eye behavior gradually increases with internal demands on general resources and that perceptual decoupling is specifically sensitive to internal demands on visuospatial resources. The latter may be mediated by interference due to eye behavior elicited by the internal task itself. Internal tasks did not affect the saccade latency-deviation trade-off, indicating that while the internal tasks delayed the execution of the saccade, the perception of the saccade stimuli and spatial planning of the saccade continued unaffected in parallel to the internal tasks. Together, these findings shed further light on the specific mechanisms underlying perceptual decoupling by suggesting that perceptual decoupling of eye behavior increases as internal demands on cognitive resources overlap more strongly with demands of the external task.

ObjectivesProlonged or excessive stress can have a negative impact on health and well-being, and stress therefore constitutes a major public health issue. A central question is what are the main sources of stress in contemporary societies? This study examines the effects of work-related and non-work-related stressors and perceived social support on perceived stress within a causal framework.MethodsPanel data were drawn from two waves (2013 and 2017) of the population-based health survey "How are you?" conducted in the Central Denmark Region. The analytical sample comprised 9,194 subjects who had responded to both surveys. Work-related and non-work-related stressors included major life events, chronic stressors, daily hassles and lack of social support. Perceived stress was measured with the 10-item Perceived Stress Scale (PSS). Data were analysed using fixed effects regression in a fully balanced design.ResultsThe largest effects on PSS were seen in own disease, work situation and lack of social support. Other stressors affecting the perceived stress level were financial circumstances, relationship with partner, relationship with family and friends, and disease among close relatives. Most variables had a symmetrical effect on PSS.ConclusionsThe results point to the need for comprehensive policies to promote mental health that span life domains and include both the individual and the group as well as organizational and societal levels. The study indicates that there are multiple potential entry points for stress prevention and stress management. However, it also shows that disease, work situation and social support weigh heavily in the overall picture. This points to the healthcare system and workplace as key institutional venues for action.

Obscurin is a giant muscle protein (>800 kDa) featuring multiple signalling domains, including an SH3-DH-PH domain triplet from the Trio-subfamily of guanosine nucleotide exchange factors (GEFs). While previous research suggests that these domains can activate the small GTPases RhoA and RhoQ in cells, in vitro characterization of these interactions using biophysical techniques has been hampered by the intrinsic instability of obscurin GEF domains. To study substrate specificity, mechanism and regulation of obscurin GEF function by individual domains, we successfully optimized recombinant production of obscurin GEF domains and found that MST-family kinases phosphorylate the obscurin DH domain at Thr5798. Despite extensive testing of multiple GEF domain fragments, we did not detect any nucleotide exchange activity in vitro against 9 representative small GTPases. Bioinformatic analyses show that obscurin differs from other Trio-subfamily GEFs in several important aspects. While further research is necessary to evaluate obscurin GEF activity in vivo, our results indicate that obscurin has atypical GEF domains that, if catalytically active at all, are subject to complex regulation.

BackgroundThe differentiation of minimal-fat-or low-fat-angiomyolipomas from other renal lesions is clinically challenging in conventional computed tomography. In this work, we have assessed the potential of grating-based x-ray phase-contrast computed tomography (GBPC-CT) for visualization and quantitative differentiation of minimal-fat angiomyolipomas (mfAMLs) and oncocytomas from renal cell carcinomas (RCCs) on ex vivo renal samples.Materials and methodsLaboratory GBPC-CT was performed at 40 kVp on 28 ex vivo kidney specimens including five angiomyolipomas with three minimal-fat (mfAMLs) and two high-fat (hfAMLs) subtypes as well as three oncocytomas and 20 RCCs with eight clear cell (ccRCCs), seven papillary (pRCCs) and five chromophobe RCC (chrRCC) subtypes. Quantitative values of conventional Hounsfield units (HU) and phase-contrast Hounsfield units (HUp) were determined and histogram analysis was performed on GBPC-CT and grating-based attenuation-contrast computed tomography (GBAC-CT) slices for each specimen. For comparison, the same specimens were imaged at a 3T magnetic resonance imaging (MRI) scanner.ResultsWe have successfully matched GBPC-CT images with clinical MRI and histology, as GBPC-CT presented with increased soft tissue contrast compared to absorption-based images. GBPC-CT images revealed a qualitative and quantitative difference between mfAML samples (58±4 HUp) and oncocytomas (44±10 HUp, p = 0.057) and RCCs (ccRCCs: 40±12 HUp, p = 0.012; pRCCs: 43±9 HUp, p = 0.017; chrRCCs: 40±7 HUp, p = 0.057) in contrast to corresponding laboratory attenuation-contrast CT and clinical MRI, although not all differences were statistically significant. Due to the heterogeneity and lower signal of oncocytomas, quantitative differentiation of the samples based on HUp or in combination with HUs was not possible.ConclusionsGBPC-CT allows quantitative differentiation of minimal-fat angiomyolipomas from pRCCs and ccRCCs in contrast to absorption-based imaging and clinical MRI.

Misinformation has emerged as a major societal concern. But why do citizens contribute to the dissemination of falsehoods online? This article investigates this question by focusing on the role of motivated reasoning and, in particular, perceptions of group-based conflict. It examines the effect of perceived conflict on the endorsement of false news in the context of a regional conflict between Russia and the West as experienced by Ukrainian citizens. In our survey experiment, a sample of Ukrainians (N = 1,615) was randomly assigned to read negative false news stories about Russia, the European Union or Tanzania–a country with no stakes in the conflict. The results show that higher perceived conflict between Ukraine and Russia makes Ukrainians less likely to endorse false news targeting the European Union, but more likely to endorse false news that paint a negative picture of Russia. This finding extends the support for motivated reasoning theory beyond Western contexts investigated so far. Importantly, the effects of conflict perceptions remain strong after controlling for group identity and political knowledge of participants. These results advance our understanding of why false information is disseminated and point to the importance of conflict de-escalation to prevent the diffusion of falsehoods.

Valvometry techniques used to monitor bivalve gaping activity have elucidated numerous relationships with environmental fluctuations, along with biological rhythms ranging from sub-daily to seasonal. Thus, a precise understanding of the natural activity of bivalves (i.e., not exposed to stressful environmental variations) is necessary as a baseline for detecting abnormal behaviors (deviations). This knowledge is also needed to reliably interpret observations of bivalve gaping behavior and associated biological processes (e.g., respiration, nutrition) acquired over time-limited periods. With this in mind, we investigated the natural daily gaping activity of the great scallop (Pecten maximus) by continuously monitoring 35 individuals in several individual tanks and in situ (Bay of Saint-Brieuc, Brittany, France) using fully autonomous Hall effect sensors. Our results revealed a circadian cycle (τ = 24.0h) in scallop gaping activity. Despite significant inter-individual variability in mean opening and cycle amplitude, almost all individuals (87.5%) exhibited nocturnal activity, with valves more open at night than during the day. A shift in light regime in the tanks triggered an instantaneous change in opening pattern, indicating that light levels strongly determine scallop activity. Based on the opening status of scallops, we also identified several gaping behaviors deviating from the regular daily pattern (lack of rhythmicity, high daytime opening), potentially reflecting physiological weakness. While further long-term studies are required to fully understand the natural activity of scallops, these findings pave the way for studies focused on the scallop response to external factors and introduce further research into the detection of abnormal behaviors. Coupling observations of diel valve gaping cycles with other daily variations in organismal and environmental parameters could help explain mechanisms driving the growth patterns of scallops observed in their shell striations. From a technical perspective, our field-based monitoring demonstrates the suitability of autonomous valvometry sensors for studying mobile subtidal bivalve activity in remote offshore environments.

ObjectivesTo assess the benefits and harms of cannabinoids in participants with pain.DesignSystematic review of randomised clinical trials with meta-analysis, Trial Sequential Analysis, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Data sourcesThe Cochrane Library, MEDLINE, Embase, Science Citation Index, and BIOSIS.Eligibility criteria for selecting studiesPublished and unpublished randomised clinical trials comparing cannabinoids versus placebo in participants with any type of pain.Main outcome measuresAll-cause mortality, pain, adverse events, quality of life, cannabinoid dependence, psychosis, and quality of sleep.ResultsWe included 65 randomised placebo-controlled clinical trials enrolling 7017 participants. Fifty-nine of the trials and all outcome results were at high risk of bias. Meta-analysis and Trial Sequential Analysis showed no evidence of a difference between cannabinoids versus placebo on all-cause mortality (RR 1.20; 98% CI 0.85 to 1.67; P = 0.22). Meta-analyses and Trial Sequential Analysis showed that cannabinoids neither reduced acute pain (mean difference numerical rating scale (NRS) 0.52; 98% CI -0.40 to 1.43; P = 0.19) or cancer pain (mean difference NRS -0.13; 98% CI -0.33 to 0.06; P = 0.1) nor improved quality of life (mean difference -1.38; 98% CI -11.81 to 9.04; P = 0.33). Meta-analyses and Trial Sequential Analysis showed that cannabinoids reduced chronic pain (mean difference NRS -0.43; 98% CI -0.72 to -0.15; P = 0.0004) and improved quality of sleep (mean difference -0.42; 95% CI -0.65 to -0.20; P = 0.0003). However, both effect sizes were below our predefined minimal important differences. Meta-analysis and Trial Sequential Analysis indicated that cannabinoids increased the risk of non-serious adverse events (RR 1.20; 95% CI 1.15 to 1.25; P < 0.001) but not serious adverse events (RR 1.18; 98% CI 0.95 to 1.45; P = 0.07). None of the included trials reported on cannabinoid dependence or psychosis.ConclusionsCannabinoids reduced chronic pain and improved quality of sleep, but the effect sizes are of questionable importance. Cannabinoids had no effects on acute pain or cancer pain and increased the risks of non-serious adverse events. The harmful effects of cannabinoids for pain seem to outweigh the potential benefits.

BackgroundThe dose-limiting effect of CT-assessed low skeletal muscle mass (LSMM) measured at the level of the third cervical vertebra has been found in head and neck cancer patients receiving high-dose cisplatin chemoradiotherapy. The aim of this study was to investigate the predictive factors for dose-limiting toxicities (DLTs) using low-dose weekly chemoradiotherapy.Materials and methodsHead and neck cancer patients receiving definite chemoradiotherapy with weekly 40 mg/m2 body surface area (BSA) cisplatin or paclitaxel 45 mg/m2 BSA and carboplatin AUC2 were consecutively included and retrospectively analysed. Skeletal muscle mass was assessed using the muscle surface at the level of the third cervical vertebra in pretherapeutic CT scans. After stratification for LSMM DLT, acute toxicities and feeding status during the treatment were examined.ResultsDose-limiting toxicity was significantly higher in patients with LSMM receiving cisplatin weekly chemoradiotherapy. For paclitaxel/carboplatin, no significance regarding DLT and LSMM could be found. Patients with LSMM had significantly more dysphagia before treatment, although feeding tube placement before treatment was equal in patients with and without LSMM.ConclusionsLSMM is a predictive factor for DLT in head and neck patients treated with low-dose weekly chemoradiotherapy with cisplatin. For paclitaxel/carboplatin, further research must be carried out.

Meiotic recombination is a crucial cellular process, being one of the major drivers of evolution and adaptation of species. In plant breeding, crossing is used to introduce genetic variation among individuals and populations. While different approaches to predict recombination rates for different species have been developed, they fail to estimate the outcome of crossings between two specific accessions. This paper builds on the hypothesis that chromosomal recombination correlates positively to a measure of sequence identity. It presents a model that uses sequence identity, combined with other features derived from a genome alignment (including the number of variants, inversions, absent bases, and CentO sequences) to predict local chromosomal recombination in rice. Model performance is validated in an inter-subspecific indica x japonica cross, using 212 recombinant inbred lines. Across chromosomes, an average correlation of about 0.8 between experimental and prediction rates is achieved. The proposed model, a characterization of the variation of the recombination rates along the chromosomes, can enable breeding programs to increase the chances of creating novel allele combinations and, more generally, to introduce new varieties with a collection of desirable traits. It can be part of a modern panel of tools that breeders can use to reduce costs and execution times of crossing experiments.

Lipoprotein(a), also known as Lp(a), is an LDL-like particle composed of apolipoprotein(a) (apo(a)) bound covalently to apolipoprotein B100. Plasma concentrations of Lp(a) are highly heritable and vary widely between individuals. Elevated plasma concentration of Lp(a) is considered as an independent, causal risk factor of cardiovascular disease (CVD). Targeted mass spectrometry (LC-SRM/MS) combined with stable isotope-labeled recombinant proteins provides robust and precise quantification of proteins in the blood, making LC-SRM/MS assays appealing for monitoring plasma proteins for clinical implications. This study presents a novel quantitative approach, based on proteotypic peptides, to determine the absolute concentration of apo(a) from two microliters of plasma and qualified according to guideline requirements for targeted proteomics assays. After optimization, assay parameters such as linearity, lower limits of quantification (LLOQ), intra-assay variability (CV: 4.7%) and inter-assay repeatability (CV: 7.8%) were determined and the LC-SRM/MS results were benchmarked against a commercially available immunoassay. In summary, the measurements of an apo(a) single copy specific peptide and a kringle 4 specific peptide allow for the determination of molar concentration and relative size of apo(a) in individuals.

Introduction Two next-generation pneumococcal conjugate vaccines (PCVs), a 15- and a 20-valent PCV (PCV15 and PCV20), have recently been licensed for use in adults, and PCV15 has also been licensed in children. We developed a dynamic transmission model specific for Germany, with the aim to predict carriage prevalence and invasive pneumococcal disease (IPD) burden for serotypes included in these vaccines. Methods The model allows to follow serotype distributions longitudinally both in the absence and presence of PCV vaccinations. We considered eight age cohorts and seven serotype groups according to the composition of different pneumococcal vaccines. This comprises the additional serotypes contained in PCV15 and PCV20 but not in PCV13. Results The model predicted that by continuing the current vaccine policy (standard vaccination with PCV13 in children and with PPSV23 in adults) until 2031, IPD case counts due to any serotype in children Conclusions We conclude that introduction of next-generation PCVs for adults may prevent a substantial and increasing proportion of adult IPDs, with PCV20 having the potential to provide the broadest protection against pneumococcal disease.

In immersive Virtual Reality (VR), users can experience the subjective feeling of embodiment for the avatar representing them in a virtual world. This is known to be strongly supported by a high Sense of Agency (SoA) for the movements of the avatar that follows the user. In general, users do not self-attribute actions of their avatar that are different from the one they actually performed. The situation is less clear when actions of the avatar satisfies the intention of the user despite distortions and noticeable differences between user and avatar movements. Here, a within-subject experiment was condutected to determine wether a finger swap helping users to achieve a task would be more tolerated than one penalizing them. In particular, in a context of fast-paced finger movements and with clear correct or incorrect responses, we swapped the finger animation of the avatar (e.g. user moves the index finger, the avatar moves the middle one) to either automatically correct for spontaneous mistakes or to introduce incorrect responses. Subjects playing a VR game were asked to report when they noticed the introduction of a finger swap. Results based on 3256 trials (∼24% of swaps noticed) show that swaps helping users have significantly fewer odds of being noticed (and with higher confidence) than the ones penalizing users. This demonstrates how the context and the intention for motor action are important factors for the SoA and for embodiment, opening new perspectives on how to design and study interactions in immersive VR.

Nod-Like Receptor Pyrin domain-containing protein 6 (NLRP6), a member of the Nucleotide-oligomerization domain-Like Receptor (NLR) family of proteins, assembles together with the ASC protein to form an inflammasome upon stimulation by bacterial lipoteichoic acid and double-stranded DNA. Besides its expression in myeloid cells, NLRP6 is also expressed in intestinal epithelial cells where it may contribute to the maintenance of gut homeostasis and negatively controls colorectal tumorigenesis. Here, we report that NLRP6 is very faintly expressed in several colon cancer cell lines, detected only in cytoplasmic small dots were it colocalizes with ASC. Consequently, it is very hardly detected by standard western-blotting techniques by several presently available commercial antibodies which, in contrast, highly cross-react with a protein of 90kDa that we demonstrate to be unrelated to NLRP6. We report here these results to caution the community not to confuse the 90kDa protein with the endogenous human NLRP6.

The overall goal of this study is to explore the rollout of the community health policy in Guinea in the context of decentralization, and the role of decision space (the decision authority, capacities, and accountability of local officials) in explaining gaps between the policy's conceptualization and actual implementation. The implementation research study will employ a sequential explanatory mixed-methods design. The study will be conducted in 27 communes purposefully selected across the country and include communes where the national community health policy is fully, partially, and not yet being implemented. The quantitative component, based on a survey questionnaire and secondary data, will use ordinary least squares (OLS) multiple regression to compare maternal and child health (MCH) coverage indicators according to the level of policy implementation in the commune. An interrupted time series analysis will be conducted to assess changes in routine MCH service delivery indicators associated with implementation of the community health policy, comparing indicators from one year prior to implementation. OLS regression will be conducted to assess the association between decision space and MCH indicators; all analyses will be carried out in Stata. Findings from the quantitative study will be used to inform the key qualitative questions and areas to explore in greater depth, to develop the interview and focus group guides, and to generate an initial codebook. Qualitative data will be double coded in NVivo by two qualitative analysts, and results generated using thematic analysis. Findings from the quantitative and qualitative components will be integrated and triangulated for interpretation and reporting. Findings and recommendations of this study will inform revisions to the National Community Health Policy to improve its rollout and effectiveness.

ObjectiveRezum is a minimal invasive surgical treatment for patients with lower urinary tract symptoms (LUTS) related to benign prostatic enlargement (BPE). The aim of our study was to assess safety and efficacy of the Rezum procedure in a consecutive series of patients.Material and methodsA retrospective study was performed in a single tertiary care hospital in patients undergoing Rezum procedure between 2018 and 2020. All patients that underwent intervention because of drug-refractory moderate to severe LUTS were assessed. Descriptive outcomes such as symptoms scores (IPSS, IPSS-QoL), peak flow in uroflowmetry (Qmax), post-micturition residual urine volume (PVR) and prostate volume (PVol) were analysed.ResultsIn total, 92 Rezum procedures were performed in the observational period. All interventions were competed without device- or procedure relates adverse events. Patients achieved a significant symptom relief as measured in IPSS (50% reduction, pConclusionRezum therapy is safe and effective and can be considered a viable treatment option for BPH related LUTS.