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Measurement and Modeling of Polarized Atmosphere at the South Pole with SPT-3G
No full textWe present the detection and characterization of fluctuations in linearly polarized emission from the atmosphere above the South Pole. These measurements make use of data from the SPT-3G receiver on the South Pole Telescope in three frequency bands centered at 95, 150, and 220 GHz. We use the cross-correlation between detectors to produce an unbiased estimate of the power in Stokes I, Q, and U parameters on large angular scales. Our results are consistent with the polarized signal being produced by the combination of Rayleigh scattering of thermal radiation from the ground and thermal emission from a population of horizontally aligned ice crystals with an anisotropic distribution described by Kolmogorov turbulence. The measured spatial scaling, frequency scaling, and elevation dependence of the polarized emission are explained by this model. Polarized atmospheric emission has the potential to significantly impact observations on the large angular scales being targeted by searches for inflationary B-mode CMB polarization. We present the distribution of measured angular power spectrum amplitudes in Stokes Q and I for 4 yr of Austral winter observations, which can be used to simulate the impact of atmospheric polarization and intensity fluctuations at the South Pole on a specified experiment and observation strategy. We present a mitigation strategy that involves both downweighting significantly contaminated observations and subtracting a polarized atmospheric signal from the 150 GHz band maps. In observations with the SPT-3G instrument, the polarized atmospheric signal is a well-understood and subdominant contribution to the measured noise after implementing the mitigation strategies described here
SARS-CoV-2 infection rates and associated risk factors in healthcare workers: systematic review and meta-analysis
No full textTo protect healthcare workforce during the COVID-19 pandemic, rigorous efforts were made to reduce infection rates among healthcare workers (HCWs), especially prior to vaccine availability. This study aimed to investigate the prevalence of SARS-CoV-2 infections among HCWs and identify potential risk factors associated with transmission. We searched MEDLINE, Embase, and Google Scholar from 1 December 2019 to 5 February 2024. From 498 initial records, 190 articles were reviewed, and 63 studies were eligible. ROBINS-E tool revealed a lower risk of bias in several domains; however, some concerns related to confounding and exposure measurement were identified. Globally, 11% (95% confidence interval (CI) 9–13) of 283,932 HCWs were infected with SARS-CoV-2. Infection rates were associated with a constellation of risk factors and major circulating SARS-CoV-2 variants. Household exposure (odds ratio (OR) 7.07; 95% CI 3.93–12.73), working as a cleaner (OR 2.72; 95% CI 1.39–5.32), occupational exposure (OR 1.79; 95% CI 1.49–2.14), inadequate training on infection prevention and control (OR 1.46; 95% CI 1.14–1.87), insufficient use of personal protective equipment (OR 1.45; 95% CI 1.14–1.84), performing aerosol generating procedures (OR 1.36; 95% CI 1.21–1.52) and inadequate hand hygiene (OR 1.17; 95% CI 0.79–1.73) were associated with an increased SARS-CoV-2 infection. Conversely, history of quarantine (OR 0.23; 95% CI 0.08–0.60) and frequent decontamination of high touch areas (OR 0.52; 95% CI 0.42–0.64) were protective factors against SARS-CoV-2 infection. This study quantifies the substantial global burden of SARS-CoV-2 infection among HCWs. We underscore the urgent need for effective infection prevention and control measures, particularly addressing factors such as household exposure and occupational practices by HCWs, including cleaning staff
MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration
No full textSpecialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015. Since its conception, MIBiG has been regularly updated to expand data coverage and remain up to date with innovations in natural product research. Here, we describe MIBiG version 4.0, an extensive update to the data repository and the underlying data standard. In a massive community annotation effort, 267 contributors performed 8304 edits, creating 557 new entries and modifying 590 existing entries, resulting in a new total of 3059 curated entries in MIBiG. Particular attention was paid to ensuring high data quality, with automated data validation using a newly developed custom submission portal prototype, paired with a novel peer-reviewing model. MIBiG 4.0 also takes steps towards a rolling release model and a broader involvement of the scientific community. MIBiG 4.0 is accessible online at https://mibig.secondarymetabolites.org/
Graded changes in local functional connectivity of the cerebral cortex in young people with depression
No full textBackground Major depressive disorder (MDD) is marked by significant changes to the local synchrony of spontaneous neural activity across various brain regions. However, many methods for assessing this local connectivity use fixed or arbitrary neighborhood sizes, resulting in a decreased capacity to capture smooth changes to the spatial gradient of local correlations. A newly developed method sensitive to classical anatomo-functional boundaries, Iso-Distant Average Correlation (IDAC), was therefore used to examine depression associated alterations to the local functional connectivity of the brain. Method One-hundred and forty-seven adolescents and young adults with MDD and 94 healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI) scan. Whole-brain functional connectivity maps of intracortical neural activity within iso-distant local areas (5-10, 15-20, and 25-30 mm) were generated to characterize local fMRI signal similarities. Results Across all spatial distances, MDD participants demonstrated greater local functional connectivity of the bilateral posterior hippocampus, retrosplenial cortex, dorsal insula, fusiform gyrus, and supplementary motor area. Local connectivity alterations in short and medium distances (5-10 and 15-20 mm) in the mid insula cortex were additionally associated with expressive suppression use, independent of depressive symptom severity. Conclusions Our study identified increased synchrony of the neural activity in several regions commonly implicated in the neurobiology of depression. These effects were relatively consistent across the three distances examined. Longitudinal investigation of this altered local connectivity will clarify whether these differences are also found in other age groups and if this relationship is modified by increased disease chronicity
Longitudinal Genomic Analysis to Fine-tune Targeted Therapy: Results of the Phase II LOGIC 2 Trial in Patients with BRAFV600-Mutant Metastatic Melanoma
No full textPURPOSE: LOGIC 2 (NCT02159066), a multicenter, open-label, two-part, phase II study, assessed encorafenib plus binimetinib combined with a third targeted agent after tumor progression on encorafenib plus binimetinib in patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma. PATIENTS AND METHODS: Adults with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma who were BRAF inhibitor/MEK inhibitor (BRAFi/MEKi) treatment-naïve or pretreated received encorafenib plus binimetinib (part I/run-in). Based on the genomic testing at disease progression following encorafenib plus binimetinib, patients were assigned to one of four treatment arms to receive encorafenib plus binimetinib with an appropriate molecularly targeted agent (ribociclib, infigratinib, capmatinib, or buparlisib; part II). The primary endpoint was best overall response; safety, biomarkers, pharmacokinetics, and other efficacy endpoints were also assessed. RESULTS: In part I/run-in, 75 BRAFi/MEKi-naïve patients and 83 BRAFi/MEKi-pretreated patients were treated; in part II, 58 patients were treated (ribociclib, n = 38; infigratinib, n = 1; capmatinib, n = 13; buparlisib, n = 6). The overall confirmed response rate was 73.3% [95% confidence interval (CI), 61.9-82.9] in BRAFi/MEKi-naïve patients, 25.3% (95% CI, 16.4-36.0) in pretreated patients, 2.6% (95% CI, 0.1-13.8) in the ribociclib arm, and 0% in the other three arms. Adverse events were manageable and consistent with the known safety profile of each drug. CONCLUSIONS: LOGIC 2 supports the use of encorafenib plus binimetinib for treatment-naïve and previously treated, locally advanced, unresectable or metastatic BRAFV600-mutant melanoma. However, adding a third targeted agent following disease progression did not show meaningful efficacy; further research is needed to identify other therapeutic targets to circumvent resistance
Global and regional disparities in access to specialist sarcoma services.
No full textAIMS: Cancer care guidelines have been developed in many subspecialities, usually in advanced health systems. However, there are notable global disparities in healthcare access, which can impact sarcoma care. Unfortunately, there is a lack of global data on this subject. Our aim was to describe access to sarcoma care based on a comprehensive global survey among orthopaedic oncologists, and assess for global as well as regional differences. METHODS: A 25-question survey was emailed to the attendees of the 2024 Birmingham Orthopaedic Oncology Meeting and included questions about the respondents' training and practice, access to sarcoma centres, and specific items for sarcoma diagnosis and treatment. For data analysis and comparison, countries were grouped geographically and per the World Bank's income classification. RESULTS: A total of 192 specialists from 47 countries completed the survey (67%). Overall, 40% declared that most patients in their country were treated in a specialized sarcoma centre. Declared access to specific diagnostic technology ranged from 69% (translocation studies) to 86% (various immunohistochemistry). Only 31% stated having access to proton therapy and 82% to all possible reconstruction methods. Compromise of ideal surgical management because of prior treatments and financial constraints was declared to have happened regularly in 40% and 17% of practices, respectively. Regions with better-developed healthcare systems had improved access to all aspects surveyed. Similar results were observed when comparing high-income countries against low- to middle-income countries. CONCLUSION: Our study highlights substantial global and regional disparities in access to sarcoma services, which could potentially impact clinical outcomes. Further studies are needed to clarify this reality
Mature forest habitat mitigates the decline of an endangered greater glider population through a widespread disturbance event
No full textGlobally, forests support more than two-thirds of extant mammal species. Land clearing, logging and fire are prevalent disturbance mechanisms that reduce forest cover. However, impacts from severe storm events may also seriously impact forests and the mammals they contain. Despite predictions that storms may become more frequent and severe under anthropogenic climate change, little is known about how these disturbance events impact mammal species. In Victoria, Australia, the Wombat Forest supports a population of the endangered arboreal marsupial, the southern Greater Glider (Petauroides volans), which is isolated from the main part of the species’ distribution. A major storm event in June 2021 felled large swathes of trees, significantly impacting the Wombat Forest. We sought to investigate the effect of key habitat components on the abundance of Greater Gliders, and which factors exacerbate or mitigate the impact of the storm event on Greater Glider abundance. We monitored forty-two sites pre- and post- storm through double-observer spotlighting and applied a mark-recapture distance-sampling (MRDS) model to calculate detection probability and abundance-level parameters. The abundance of the Greater Glider was higher with increased levels of mature forest, including dead trees, and higher basal areas of food trees (Eucalyptus dalrympleana/cypellocarpa and Eucalyptus radiata). Wetter microclimates (e.g. gullies) as well as the lack of recent fire (in the preceding 40 years) also corresponded to higher abundance. The storm led to a decline in abundance of approximately a third (-39.0 % [90 % CI: −49.1 %, −27.1 %]) within sampled areas. This change in abundance is predicted to have reduced the population from 13,549 [90 % CI: 10,495, 17,776] to 8560 [90 % CI: 6489, 11,565] individuals within the Wombat Forest study area (374.6 km2). However, mature forest habitat (as indicated by the median DBH of trees) had a mitigating effect on the decline in Greater Glider abundance between pre- and post-storm surveys. This means that mature habitat not only increases Greater Glider abundance but also enhances their ability to persist through disturbance events. The predicted impacts of the storms and changing climates place the Wombat Forest population at risk of further decline. Retention of mature forest can be a strategy to maintain the density of Greater Glider populations facing future disturbance events
Making sense of the virome in light of evolution and ecology
No full textUnderstanding the patterns and drivers of viral prevalence and abundance is of key importance for understanding pathogen emergence. Over the last decade, metagenomic sequencing has exponentially expanded our knowledge of the diversity and evolution of viruses associated with all domains of life. However, as most of these 'virome' studies are primarily descriptive, our understanding of the predictors of virus prevalence, abundance and diversity, and their variation in space and time, remains limited. For example, we do not yet understand the relative importance of ecological predictors (e.g. seasonality and habitat) versus evolutionary predictors (e.g. host and virus phylogenies) in driving virus prevalence and diversity. Few studies are set up to reveal the factors that predict the virome composition of individual hosts, populations or species. In addition, most studies of virus ecology represent a snapshot of single species viromes at a single point in time and space. Fortunately, recent studies have begun to use metagenomic data to directly test hypotheses about the evolutionary and ecological factors which drive virus prevalence, sharing and diversity. By synthesizing evidence across studies, we present some over-arching ecological and evolutionary patterns in virome composition, and illustrate the need for additional work to quantify the drivers of virus prevalence and diversity
PSKH1 kinase activity is differentially modulated via allosteric binding of Ca2+ sensor proteins
No full textProtein Serine Kinase H1 (PSKH1) was recently identified as a crucial factor in kidney development and is overexpressed in prostate, lung, and kidney cancers. However, little is known about PSKH1 regulatory mechanisms, leading to its classification as a "dark" kinase. Here, we used biochemistry and mass spectrometry to define PSKH1's consensus substrate motif, protein interactors, and how interactors, including Ca2+ sensor proteins, promote or suppress activity. Intriguingly, despite the absence of a canonical Calmodulin binding motif, Ca2+-Calmodulin activated PSKH1 while, in contrast, the ER-resident Ca2+ sensor of the Cab45, Reticulocalbin, Erc55, Calumenin (CREC) family, Reticulocalbin-3, suppressed PSKH1 catalytic activity. In addition to antagonistic regulation of the PSKH1 kinase domain by Ca2+ sensing proteins, we identified UNC119B as a protein interactor that activates PSKH1 via direct engagement of the kinase domain. Our findings identify complementary allosteric mechanisms by which regulatory proteins tune PSKH1's catalytic activity and raise the possibility that different Ca2+ sensors may act more broadly to tune kinase activities by detecting and decoding extremes of intracellular Ca2+ concentrations
Dietary Zinc Limitation Dictates Lifespan and Reproduction Trade-Offs of Drosophila Mothers
No full textDietary metal ions significantly influence the lifespan and reproduction of Drosophila females. In this study, we show that not adding any of the metal ions to the diet adversely affects reproduction and lifespan. By contrast, food with no added Zn negatively impacts reproduction but does not adversely affect maternal lifespan, indicating it can dictate resource reallocation between key fitness traits. Specifically, it indicates that female flies stop producing eggs to conserve their body Zn for somatic maintenance. Although these data show that flies can sense varying dietary Zn levels to adjust their physiology, they cannot maximise egg production when faced with a choice between food with no added Zn or food with sufficient Zn to support maximum reproduction. Nonetheless, they can choose to preferentially oviposit on Zn-containing food, perhaps indicating a strategy to assure offspring survival. We also uncovered a role for the white gene in sustaining high levels of egg viability when Zn is diluted in the diet. These insights into the role of dietary metal ions, particularly Zn, point to a central role for these dietary micronutrients to indicate environmental quality and so govern trade-offs between lifespan and reproduction in flies