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Skeletal dysplasias (SDs) are a broad and heterogeneous group of genetic disorders primarily affecting bone and collagen development. Diastrophic dysplasia (DTD) is a rare autosomal recessive chondrodysplasia caused by biallelic variants in the SLC26A2 gene. The current study aims to assess the clinical and molecular findings in Egyptian patients with DTD. This study enrolled fifteen patients who were clinically diagnosed with DTD. Exome sequencing identified nine homozygous variants in the SLC26A2 gene across ten patients; five of these variants were novel (p.Cys78Gly, p.Leu132Pro, p.Asp177Tyr, p.Thr546Ala, and p.Leu554Phe), while four had been previously reported. Novel variants were confirmed using Sanger sequencing and were predicted to be disease-causing based on in silico analyses and structural protein modeling. The exome sequencing analysis did not reveal any additional candidate genes that could contribute to the clinical phenotype in patients with negative SLC26A4 causative variants. Our findings expand the spectrum of variants associated with DTD, which may aid in early diagnosis and counseling for affected families. Further studies are needed to confirm computational predictions of novel variants and their consequences in disease mechanisms, and to identify causative genes in the undiagnosed cases.

Science education and environmental education are important gates to prepare the next generation for our society’s current and upcoming challenges. While in the informal sector, environmental education acts independently, on the formal side, science education hosts environmental issues within its interdisciplinary context. As both educational efforts traditionally bear different emphases, the question may arise of whether formal science classes can act as an appropriate host. Against the background of the declining motivation to learn science in secondary school, possible synergies between both educational efforts may have vanished. For an investigation of such linkages between science motivation and environmental perception, we monitored adolescents’ motivation to learn sciences and their environmental values. By analyzing data from 429 Irish secondary school students, we reconfirmed existing scales by using confirmatory factor analysis (CFA) and investigated potential relations via SEM. Besides gender differences, we identified a significant relationship between positive ‘green’ attitude sets and the individual motivation to learn science—positive environmental preferences predict a high science motivation, primarily intrinsic motivation. Taking advantage of this relationship, individual motivation may find support from environmental educational initiatives with the focus on green values. Especially girls, who evidentially tend to have a lower motivation in science learning, may be addressed in that way.

Our objective was to further the understanding of the process of reintegration of childhood cancer patients after treatment and to identify factors influencing that process. Using a qualitative approach, we conducted 49 interviews with parents (n = 29 mothers, n = 20 fathers) from 31 families with a child (<18 years) with leukemia or CNS tumor. Interviews were conducted about 16 to 24 months after the end of the treatment. We used a semi-structured interview guideline and analyzed the data using content analysis. Average age of pediatric cancer patients was 5.5 years at the time of diagnosis; mean time since diagnosis was 3.5 years. Parents reported immediate impact of the disease on their children. Reintegration had gone along with delayed nursery/school enrollment or social challenges. In most cases reintegration was organized with a gradual increase of attendance. Due to exhaustion by obligatory activities, reintegration in leisure time activities was demanding and parents reported a gradual increase of activity level for their children. Parents described several barriers and facilitators influencing the reintegration process into nursery/school and leisure time activities (structural support, social support, health status, intrapersonal aspects). Although many children reintegrate well, the process takes lots of effort from parents and children. Childhood cancer survivors and their families should be supported after the end of intensive treatment to facilitate reintegration.

Purpose Immunotherapy is an evolving therapeutic approach for non-small cell lung cancer (NSCLC). This study explored factors involved in patients’ perceptions about reporting or not reporting treatment-related symptoms experienced while undergoing immunotherapy. Methods Patients receiving immunotherapy for NSCLC were recruited in the USA and Europe. Qualitative interviews were conducted to elicit treatment-related symptoms and explore patients’ reasons and motivations for either reporting or not reporting these to their medical teams. Interviews were audio-recorded, transcribed, and coded for qualitative analysis. Results Sixty-six patients were interviewed (mean age: 62 years; 55% male; 91% with stage IV NSCLC). The most frequent symptoms that patients experienced but did not report were gastrointestinal (23% of patients), respiratory (17%), and energy related (12%). The most common reasons for not reporting symptoms included a perception that they were not severe enough, being unsure whether the experiences were side effects, and deciding that the experiences were expected and could be managed without assistance. Fear of having treatment discontinued was also mentioned but was not a prominent reason. The most common reasons for reporting symptoms were to ascertain if these were normal and expected, and to let the medical team know. Patients emphasized the importance of survival over treatment burden when balancing symptoms with treatment benefits. Conclusion Patients have a range of reasons for not reporting their treatment-related symptoms when undergoing immunotherapy for NSCLC. Reasons are more strongly related to determination of the severity versus manageability of patients’ experiences of symptoms than they are to the fear of having treatment discontinued.

Congenital heart defects (CHDs) occur in about 1% of live births and are the leading cause of infant death due to birth defects. While there have been remarkable efforts to pursue large-scale whole-exome and genome sequencing studies on CHD patient cohorts, it is estimated that these approaches have thus far accounted for only about 50% of the genetic contribution to CHDs. We sought to take a new approach to identify genetic causes of CHDs. By combining analyses of genes that are under strong selective constraint along with published embryonic heart transcriptomes, we identified over 200 new candidate genes for CHDs. We utilized protein-protein interaction (PPI) network analysis to identify a functionally-related subnetwork consisting of known CHD genes as well as genes encoding proteasome factors, in particular POMP , PSMA6 , PSMA7 , PSMD3 , and PSMD6 . We used CRISPR targeting in zebrafish embryos to preliminarily identify roles for the PPI subnetwork genes in heart development. We then used CRISPR to create new mutant zebrafish strains for two of the proteasome genes in the subnetwork: pomp and psmd6 . We show that loss of proteasome gene functions leads to defects in zebrafish heart development, including dysmorphic hearts, myocardial cell blebbing, and reduced outflow tracts. We also identified deficits in cardiac function in pomp and psmd6 mutants. These heart defects resemble those seen in zebrafish mutants for known CHD genes and other critical heart development genes. Our study provides a novel systems genetics approach to further our understanding of the genetic causes of human CHDs.

Background Hereditary angioedema (HAE) is a genetic disorder characterized by re-occurring swelling episodes called “attacks,” usually in the limbs, face, airways, and intestinal tract. New prophylactic therapies have reduced the frequency of these attacks. This study describes results from a literature review and clinician interviews assessing patient HAE symptom experiences and timing, and then evaluates whether existing patient-reported outcome (PRO) tools adequately reflect this experience. Methods A targeted literature review as well as interviews with key opinion leaders (KOLs), were conducted to capture information about the patient experience and their symptoms. An assessment of various PROs was then conducted to determine how well they each covered HAE symptoms and impacts. Results Nineteen HAE symptoms were identified. KOLs reported that patients on prophylactic therapy experienced some symptoms indicating an attack was imminent, but then never experienced an attack. The comparison of the different PROs found that the Hereditary Angioedema Patient-Reported Outcome was the instrument that most thoroughly examined the symptoms of patients with HAE. Conclusions Given the introduction of new prophylactic therapies, further research is needed to determine the effect of being attack-free for longer periods of time on health-related quality of life.

Purpose Glioma is associated with pathologically high (peri)tumoral brain activity, which relates to faster progression. Functional connectivity is disturbed locally and throughout the entire brain, associating with symptomatology. We, therefore, investigated how local activity and network measures relate to better understand how the intricate relationship between the tumor and the rest of the brain may impact disease and symptom progression. Methods We obtained magnetoencephalography in 84 de novo glioma patients and 61 matched healthy controls. The offset of the power spectrum, a proxy of neuronal activity, was calculated for 210 cortical regions. We calculated patients’ regional deviations in delta, theta and lower alpha network connectivity as compared to controls, using two network measures: clustering coefficient (local connectivity) and eigenvector centrality (integrative connectivity). We then tested group differences in activity and connectivity between (peri)tumoral, contralateral homologue regions, and the rest of the brain. We also correlated regional offset to connectivity. Results As expected, patients’ (peri)tumoral activity was pathologically high, and patients showed higher clustering and lower centrality than controls. At the group-level, regionally high activity related to high clustering in controls and patients alike. However, within-patient analyses revealed negative associations between regional deviations in brain activity and clustering, such that pathologically high activity coincided with low network clustering, while regions with ‘normal’ activity levels showed high network clustering. Conclusion Our results indicate that pathological activity and connectivity co-localize in a complex manner in glioma. This insight is relevant to our understanding of disease progression and cognitive symptomatology.

Purpose To describe symptoms and side effects experienced by patients with advanced non-small cell lung cancer (NSCLC), assess how patients allocate sensations (i.e. symptoms or side effects) to either the disease or its treatment, and evaluate how patients balance side effects with treatment benefits. Methods Qualitative sub-studies were conducted as part of two clinical trials in patients treated for advanced NSCLC (AURA [NCT01802632]; ARCTIC [NCT02352948]). Results Interviews were conducted with 23 patients and 19 patients in the AURA and ARCTIC sub-studies, respectively. The most commonly experienced symptoms/side effects were respiratory (81% of patients), digestive (76%), pain and discomfort (76%), energy-related (71%), and sensory (62%). Patients identified a sensation as a treatment side effect if they had not experienced it before, if there was a temporal link between the sensation and receipt of treatment, and/or if their doctors consistently told or asked them about it in relation to side effects. Themes that emerged when patients talked about their cancer treatment and its side effects related to the serious nature of their advanced disease and their treatment expectations. Patients focused on treatment benefits, wanting a better quality of life, being hopeful, not really having a choice, and not thinking about side effects. Conclusions In these two qualitative sub-studies, patients with advanced NSCLC valued the benefits of their treatment regardless of side effects that they experienced. Patients weighed their options against the seriousness of their disease and expressed their willingness to tolerate their side effects in return for receiving continued treatment benefits.

The severe geomagnetic effects of solar storms or coronal mass ejections (CMEs) are to a large degree determined by their propagation direction with respect to Earth. There is a lack of understanding of the processes that determine their non-radial propagation. Here we present a synthesis of data from seven different space missions of a fast CME, which originated in an active region near the disk centre and, hence, a significant geomagnetic impact was forecasted. However, the CME is demonstrated to be channelled during eruption into a direction +37±10° (longitude) away from its source region, leading only to minimal geomagnetic effects. In situ observations near Earth and Mars confirm the channelled CME motion, and are consistent with an ellipse shape of the CME-driven shock provided by the new Ellipse Evolution model, presented here. The results enhance our understanding of CME propagation and shape, which can help to improve space weather forecasts. Coronal mass ejections from the Sun play an important role in space weather, yet a full understanding of their behaviour remains elusive. Towards this aim, Möstl et al . present a suite of observations showing that an ejection was channelled away from its source region, explaining incorrect forecasts.

N. gonorrhoeae , which causes the sexually transmissible infection gonorrhoea, remains a significant public health threat globally, with challenges posed by increasing transmission and antimicrobial resistance (AMR). The COVID-19 pandemic introduced exceptional circumstances into communicable disease control, impacting the transmission of gonorrhoea and other infectious diseases. Through phylogenomic and phylodynamic analysis of 5881  N. gonorrhoeae genomes from Australia, we investigated N. gonorrhoeae transmission over five years, including a time period during the COVID-19 pandemic. Using a novel cgMLST-based genetic threshold, we demonstrate persistence of large N. gonorrhoeae genomic clusters over several years, with some persistent clusters associated with heterosexual transmission. We observed a decline in both N. gonorrhoeae transmission and genomic diversity during the COVID-19 pandemic, suggestive of an evolutionary bottleneck. The longitudinal, occult transmission of N. gonorrhoeae over many years further highlights the urgent need for improved diagnostic, treatment, and prevention strategies for gonorrhoea. Genome sequencing data can be used to infer transmission dynamics for pathogens of public health concern such as N. gonorrhoeae . Here, the authors sequence and analyse 5881 genomes from Victoria, Australia from 2017–2021, and assess impacts of COVID-19 restrictions on transmission.