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Background Mobile health (m-health) tools are a promising strategy to facilitate the work of community health workers (CHWs) in low- and middle-income countries (LMICs). Despite their potential value, little is known about CHWs’ experiences working with m-health tools in their outreach activities with community members. Methods To understand the benefits of and barriers to using m-health tools for CHWs, we conducted semi-structured interviews with 57 CHWs employed in six primary care centers in São Paulo, Brazil. All CHWs had experience using a cell phone application called Geohealth for collecting health and demographic data of community members. We assessed their experiences using Geohealth and recommendations for improvements. Results CHWs described key benefits of using Geohealth as helping them save time with bureaucratic paperwork, organizing the data that they needed to collect, and by replacing sheaves of paper, reducing the weight that they carried in the field. However, there were many technical and social barriers to the successful adoption of the m-health tool. Key among these were poor quality hardware, faulty software programs, and negative community member perceptions of the m-health program. The CHWs provided valuable input as to how Geohealth could be improved to fit their needs. Conclusion m-health tools have the potential to facilitate the work of CHWs in LMICs. However, such tools must be designed and implemented thoughtfully. Technical barriers related to both hardware and software must be anticipated and addressed to maximize their efficiency and successful adoption. CHW input on the design of the tool should be sought to maximize its utility and minimize barriers to use.

The urgency for climate action is recognised by international government and healthcare organisations, including the United Nations (UN) and World Health Organisation (WHO). Climate change, biodiversity loss, and pollution negatively impact all life on earth. All populations are impacted but not equally; the most vulnerable are at highest risk, an inequity further exacerbated by differences in access to healthcare globally. The delivery of healthcare exacerbates the planetary health crisis through greenhouse gas emissions, largely due to combustion of fossil fuels for medical equipment production and operation, creation of medical and non-medical waste, and contamination of water supplies. As representatives of radiology societies from across the globe who work closely with industry, and both governmental and non-governmental leaders in multiple capacities, we advocate together for urgent, impactful, and measurable changes to the way we deliver care by further engaging our members, policymakers, industry partners, and our patients. Simultaneous challenges including global health disparities, resource allocation, and access to care must inform these efforts. Climate literacy should be increasingly added to radiology training programmes. More research is required to understand and measure the environmental impact of radiological services and inform mitigation, adaptation and monitoring efforts. Deeper collaboration with industry partners is necessary to support innovations in the supply chain, energy utilization, and circular economy. Many solutions have been proposed and are already available, but we must understand and address barriers to implementation of current and future sustainable innovations. Finally, there is a compelling need to partner with patients, to ensure that trust in the excellence of clinical care is maintained during the transition to sustainable radiology. By fostering a culture of global cooperation and rapid sharing of solutions amongst the broader imaging community, we can transform radiological practice to mitigate its environmental impact, adapt and develop resilience to current and future climate and environmental threats, and simultaneously improve access to care.

The urgency for climate action is recognised by international government and healthcare organisations, including the United Nations (UN) and World Health Organisation (WHO). Climate change, biodiversity loss, and pollution negatively impact all life on earth. All populations are impacted but not equally; the most vulnerable are at highest risk, an inequity further exacerbated by differences in access to healthcare globally. The delivery of healthcare exacerbates the planetary health crisis through greenhouse gas emissions, largely due to combustion of fossil fuels for medical equipment production and operation, creation of medical and non-medical waste, and contamination of water supplies. As representatives of radiology societies from across the globe who work closely with industry, and both governmental and non-governmental leaders in multiple capacities, we advocate together for urgent, impactful, and measurable changes to the way we deliver care by further engaging our members, policymakers, industry partners, and our patients. Simultaneous challenges including global health disparities, resource allocation, and access to care must inform these efforts. Climate literacy should be increasingly added to radiology training programmes. More research is required to understand and measure the environmental impact of radiological services and inform mitigation, adaptation and monitoring efforts. Deeper collaboration with industry partners is necessary to support innovations in the supply chain, energy utilization, and circular economy. Many solutions have been proposed and are already available, but we must understand and address barriers to implementation of current and future sustainable innovations. Finally, there is a compelling need to partner with patients, to ensure that trust in the excellence of clinical care is maintained during the transition to sustainable radiology. By fostering a culture of global cooperation and rapid sharing of solutions amongst the broader imaging community, we can transform radiological practice to mitigate its environmental impact, adapt and develop resilience to current and future climate and environmental threats, and simultaneously improve access to care.

About 62,000 dead or dying common murres (Uria aalge), the trophically dominant fish-eating seabird of the North Pacific, washed ashore between summer 2015 and spring 2016 on beaches from California to Alaska. Most birds were severely emaciated and, so far, no evidence for anything other than starvation was found to explain this mass mortality. Three-quarters of murres were found in the Gulf of Alaska and the remainder along the West Coast. Studies show that only a fraction of birds that die at sea typically wash ashore, and we estimate that total mortality approached 1 million birds. About two-thirds of murres killed were adults, a substantial blow to breeding populations. Additionally, 22 complete reproductive failures were observed at multiple colonies region-wide during (2015) and after (2016-2017) the mass mortality event. Die-offs and breeding failures occur sporadically in murres, but the magnitude, duration and spatial extent of this die-off, associated with multi-colony and multi-year reproductive failures, is unprecedented and astonishing. These events co-occurred with the most powerful marine heatwave on record that persisted through 2014-2016 and created an enormous volume of ocean water (the \"Blob\") from California to Alaska with temperatures that exceeded average by 2-3 standard deviations. Other studies indicate that this prolonged heatwave reduced phytoplankton biomass and restructured zooplankton communities in favor of lower-calorie species, while it simultaneously increased metabolically driven food demands of ectothermic forage fish. In response, forage fish quality and quantity diminished. Similarly, large ectothermic groundfish were thought to have increased their demand for forage fish, resulting in greater top-predator demands for diminished forage fish resources. We hypothesize that these bottom-up and top-down forces created an \"ectothermic vise\" on forage species leading to their system-wide scarcity and resulting in mass mortality of murres and many other fish, bird and mammal species in the region during 2014-2017.

Neutrophilic granulocytes are able to release their own DNA as neutrophil extracellular traps (NETs) to capture and eliminate pathogens. DNA expulsion (NETosis) has also been documented for other cells and organisms, thus highlighting the evolutionary conservation of this process. Moreover, dysregulated NETosis has been implicated in many diseases, including cancer and inflammatory disorders. During NETosis, neutrophils undergo dynamic and dramatic alterations of their cellular as well as sub-cellular morphology whose biophysical basis is poorly understood. Here we investigate NETosis in real-time on the single-cell level using fluorescence and atomic force microscopy. Our results show that NETosis is highly organized into three distinct phases with a clear point of no return defined by chromatin status. Entropic chromatin swelling is the major physical driving force that causes cell morphology changes and the rupture of both nuclear envelope and plasma membrane. Through its material properties, chromatin thus directly orchestrates this complex biological process. Neutrophilic granulocytes release their own DNA (NETosis) as neutrophil extracellular traps to capture pathogens. Here, the authors use time-resolved fluorescence and atomic force microscopy and reveal that NETosis is highly organized into three distinct phases with a clear point of no return defined by chromatin status.

Transcription of non-segmented negative sense (NNS) RNA viruses follows a stop-start mechanism and is thought to be initiated at the genome’s very 3’-end. The synthesis of short abortive leader transcripts ( leader RNAs) has been linked to transcription initiation for some NNS viruses. Here, we identified the synthesis of abortive leader RNAs (as well as trailer RNAs) that are specifically initiated opposite to (anti)genome nt 2; leader RNAs are predominantly terminated in the region of nt ~ 60–80. Leader RNA synthesis requires hexamer phasing in the 3’-leader promoter. We determined a steady-state NP mRNA: leader RNA ratio of ~10 to 30-fold at 48 h after Ebola virus (EBOV) infection, and this ratio was higher (70 to 190-fold) for minigenome-transfected cells. Leader RNA initiation at nt 2 and the range of termination sites were not affected by structure and length variation between promoter elements 1 and 2, nor the presence or absence of VP30. Synthesis of leader RNA is suppressed in the presence of VP30 and termination of leader RNA is not mediated by cryptic gene end (GE) signals in the 3’-leader promoter. We further found different genomic 3’-end nucleotide requirements for transcription versus replication, suggesting that promoter recognition is different in the replication and transcription mode of the EBOV polymerase. We further provide evidence arguing against a potential role of EBOV leader RNAs as effector molecules in innate immunity. Taken together, our findings are consistent with a model according to which leader RNAs are abortive replicative RNAs whose synthesis is not linked to transcription initiation. Rather, replication and transcription complexes are proposed to independently initiate RNA synthesis at separate sites in the 3’-leader promoter, i.e., at the second nucleotide of the genome 3’-end and at the more internally positioned transcription start site preceding the first gene, respectively, as reported for Vesicular stomatitis virus.

Objectives:Endoscopist quality measures such as adenoma detection rate (ADR) and serrated polyp detection rates (SPDRs) depend on pathologist classification of histology. Although variation in pathologic interpretation is recognized, we add to the literature by quantifying the impact of pathologic variability on endoscopist performance.Methods:We used natural language processing to abstract relevant data from colonoscopy and related pathology reports performed over 2 years at four clinical sites. We quantified each pathologist's likelihood of classifying polyp specimens as adenomas or serrated polyps. We estimated the impact on endoscopists' ADR and SPDR of sending their specimens to pathologists with higher or lower classification rates.Results:We observed 85,526 colonoscopies performed by 119 endoscopists; 50,453 had a polyp specimen, which were analyzed by 48 pathologists. There was greater variation across pathologists in classification of serrated polyps than in classification of adenomas. We estimate the endoscopist's average SPDR would be 0.5% if all their specimens were analyzed by the pathologist in our sample with the lowest classification rate and 12.0% if all their specimens were analyzed by the pathologist with the highest classification rate. In contrast, the endoscopist's average ADR would be 28.5% and 42.4% if their specimens were analyzed by the pathologist with lowest and highest classification rate, respectively.Conclusions:There is significant variation in pathologic interpretation, which more substantially affects endoscopist SPDR than ADR.

Background Lymph node upstaging represents a quality criterion for standardized lymphadenectomy in lung cancer surgery. The aim of the study was to compare whether the quality of standardized lymphadenectomy in lung cancer surgery is comparable in minimally invasive (video-assisted thoracoscopic surgery) and the open approach (thoracotomy). Furthermore, factors associated with lymph node upstaging were assessed, as was its impact on overall survival and progression-free survival. Methods This retrospective study reviewed data of all patients undergoing lobectomy at the Lung Tumor Center Munich between 2011 and 2020. Inclusion factors were non-small cell lung cancer without nodal involvement (N0) or metastasis (M0) and standardized lymphadenectomy. A propensity score matched analyses was performed. Frequency of categorical outcomes was compared with Chi [ 2 ]-test, mean values with t-test. We used logistic and Cox regression models to assess factors associated with upstaging, overall survival and progression-free survival, restrictively. Results Of 1691 patients undergoing lobectomy, 637 met our inclusion criteria. After propensity score matching 198 patients remained in each group. Univariate analysis showed no significant difference in lymph node upstaging between the two groups. ( p  = 0.12). Overall affected lymph nodes ( p  = 0.45) and overall affected lymph node stations ( p  = 0.26) were not significantly different. Multivariate Cox regression analysis showed that overall survival and progression free survival were also independent of the surgical approach. L1 status was the only factor associated with progression-free survival. Conclusion Minimally invasive approaches achieves comparable lymph node upstaging in patients undergone standardized lymphadenectomy.

The fermentation characteristics of five apple and five pear varieties from non-fertilized meadow orchards (“Streuobstwiesen”) was studied. While some varieties fermented without problems, some varieties showed sluggish and stuck fermentation with high residual sugar concentration at the end of the fermentation period. A potential reason for these fermentation problems could be a poor nitrogen supply. The effect of diammonium phosphate (DAP) supplementation on the fermentation dynamics was studied over two consecutive years, with 200.0 mg/L DAP added on day 0 or day 3 of fermentation. DAP effectively prevented stuck fermentations and accelerated sluggish fermentations. In particular, in the 2021 harvest, early DAP addition reduced the fermentation time by up to 6 days. The studied pear varieties indicated a greater demand for additional nitrogen compared to apple mashes. In general, nutrient addition proved beneficial for yeast cell growth of all ten fruit mashes. These findings suggest that the correct use of DAP could enhance the fermentation process in fruit mashes with low nutrient supply, which might be crucial for producing high-quality distillates from meadow orchard fruits.

Mutations in the fused in Sarcoma ( ) gene induce cytoplasmic FUS aggregations, contributing to the neurodegenerative disease amyotrophic lateral sclerosis (ALS) in certain cases. While FUS is mainly a nuclear protein involved in transcriptional processes with limited cytoplasmic functions, it shows an additional somatodendritic localization in neurons. In this study we analyzed the localization of FUS in motoneuron synapses, these being the most affected neurons in ALS, using super-resolution microscopy to distinguish between the pre- and postsynaptic compartments. We report a maturation-based variation of FUS localization in rodent synapses where a predominantly postsynaptic FUS was observed in the early stages of synaptic development, while in mature synapses the protein was entirely localized in the axonal terminal. Likewise, we also show that at the synapse of human motoneurons derived from induced pluripotent stem cells of a healthy control, FUS is mainly postsynaptic in the early developmental stages. In motoneurons derived from ALS patients harboring a very aggressive juvenile FUS mutation, increased synaptic accumulation of mutated FUS was observed. Moreover increased aggregation of other synaptic proteins Bassoon and Homer1 was also detected in these abnormal synapses. Having demonstrated changes in the FUS localization during synaptogenesis, a role of synaptic FUS in both dendritic and axonal cellular compartments is probable, and we propose a gain-of-toxic function due to the synaptic aggregation of mutant FUS in ALS.