Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Patient Preferences for Treatment Outcomes in Oncology with a Focus on the Older Patient-A Systematic Review

For physicians, it is important to know which treatment outcomes are prioritized overall by older patients with cancer, since this will help them to tailor the amount of information and treatment recommendations. Older patients might prioritize other outcomes than younger patients. Our objective is to summarize which outcomes matter most to older patients with cancer. A systematic review was conducted, in which we searched Embase and Medline on 22 December 2020. Studies were eligible if they reported some form of prioritization of outcome categories relative to each other in patients with all types of cancer and if they included at least three outcome categories. Subsequently, for each study, the highest or second-highest outcome category was identified and presented in relation to the number of studies that included that outcome category. An adapted Newcastle-Ottawa Scale was used to assess the risk of bias. In total, 4374 patients were asked for their priorities in 28 studies that were included. Only six of these studies had a population with a median age above 70. Of all the studies, 79% identified quality of life as the highest or second-highest priority, followed by overall survival (67%), progression- and disease-free survival (56%), absence of severe or persistent treatment side effects (54%), and treatment response (50%). Absence of transient short-term side effects was prioritized in 16%. The studies were heterogeneous considering age, cancer type, and treatment settings. Overall, quality of life, overall survival, progression- and disease-free survival, and severe and persistent side effects of treatment are the outcomes that receive the highest priority on a group level when patients with cancer need to make trade-offs in oncologic treatment decisions

Patient Preferences for Treatment Outcomes in Oncology with a Focus on the Older Patient-A Systematic Review

For physicians, it is important to know which treatment outcomes are prioritized overall by older patients with cancer, since this will help them to tailor the amount of information and treatment recommendations. Older patients might prioritize other outcomes than younger patients. Our objective is to summarize which outcomes matter most to older patients with cancer. A systematic review was conducted, in which we searched Embase and Medline on 22 December 2020. Studies were eligible if they reported some form of prioritization of outcome categories relative to each other in patients with all types of cancer and if they included at least three outcome categories. Subsequently, for each study, the highest or second-highest outcome category was identified and presented in relation to the number of studies that included that outcome category. An adapted Newcastle-Ottawa Scale was used to assess the risk of bias. In total, 4374 patients were asked for their priorities in 28 studies that were included. Only six of these studies had a population with a median age above 70. Of all the studies, 79% identified quality of life as the highest or second-highest priority, followed by overall survival (67%), progression- and disease-free survival (56%), absence of severe or persistent treatment side effects (54%), and treatment response (50%). Absence of transient short-term side effects was prioritized in 16%. The studies were heterogeneous considering age, cancer type, and treatment settings. Overall, quality of life, overall survival, progression- and disease-free survival, and severe and persistent side effects of treatment are the outcomes that receive the highest priority on a group level when patients with cancer need to make trade-offs in oncologic treatment decisions.Experimentele farmacotherapi

Functional disability as an explanation of the associations between chronic physical conditions and 12-month major depressive episode

BACKGROUND: The link between physical conditions and mental health is poorly understood. Functional disability could explain the association of physical conditions with major depressive episode (MDE) as an intermediary factor. METHODS: Data was analyzed from a subsample (N=8796) of the European Study of the Epidemiology of Mental Disorders (ESEMeD), a cross-sectional general population survey. MDE during the last 12months was assessed using a revision of the Composite International Diagnostic Interview (CIDI 3.0). Lifetime chronic physical conditions were assessed by self-report. Functional disability was measured using a version of the World Health Organization Disability Assessment Schedule (WHODAS). The associations of physical conditions with MDE and explanation by functional disability were quantified using logistic regression. RESULTS: All physical conditions were significantly associated with MDE. The increases in risk of MDE ranged from 30% for allergy to amply 100% for arthritis and heart disease. When adjusted for physical comorbidity, associations decreased and were no longer statistically significant for allergy and diabetes. Functional disability explained between 17 and 64% of these associations, most substantially for stomach or duodenum ulcer, arthritis and heart disease. LIMITATIONS: Due to the cross-sectional nature of the study the temporal relationship of the variables could not be assessed and the amount of explanation cannot simply be interpreted as the amount of mediation. CONCLUSIONS: Our findings suggest that the association of chronic physical conditions with MDE is partly explained by functional disability. Such explanation is more pronounced for pain causing conditions and heart disease. Health professionals should be particularly aware of the increased risk of depressive disorder when patients experience disability from these conditions

Loss-of-function variants in SRRM2 cause a neurodevelopmental disorder

PURPOSE: SRRM2 encodes the SRm300 protein, a splicing factor of the SR-related protein family characterized by its serine- and arginine-enriched domains. It promotes interactions between messenger RNA and the spliceosome catalytic machinery. This gene, predicted to be highly intolerant to loss of function (LoF) and very conserved through evolution, has not been previously reported in constitutive human disease. METHODS: Among the 1000 probands studied with developmental delay and intellectual disability in our database, we found 2 patients with de novo LoF variants in SRRM2. Additional families were identified through GeneMatcher. RESULTS: Here, we report on 22 patients with LoF variants in SRRM2 and provide a description of the phenotype. Molecular analysis identified 12 frameshift variants, 8 nonsense variants, and 2 microdeletions of 66 kb and 270 kb. The patients presented with a mild developmental delay, predominant speech delay, autistic or attention-deficit/hyperactivity disorder features, overfriendliness, generalized hypotonia, overweight, and dysmorphic facial features. Intellectual disability was variable and mild when present. CONCLUSION: We established SRRM2 as a gene responsible for a rare neurodevelopmental disease

Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities.

PURPOSE: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder. METHODS: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature. RESULTS: The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss. CONCLUSION: This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities

Histone H3.3 beyond cancer: Germline mutations in<em> Histone 3 Family 3A</em> and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation