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PurposeThe Swedish Pancreatitis Cohort (SwePan) was designed to study long-term outcomes following an episode of acute pancreatitis. It can also be used to study various risk factors for developing acute pancreatitis.ParticipantsThe SwePan is a register-based nationwide matched cohort. It includes all Swedish cases of acute pancreatitis during 1990–2019. It contains 95 632 individuals with acute pancreatitis and 952 783 pancreatitis-free individuals matched on sex, age and municipality of residence. Follow-up was censored at death, emigration or end of study (31 December 2019). The dataset includes comprehensive information based on several registries, and includes diagnoses, prescribed medications and socioeconomic factors both prior to inclusion and during follow-up.Findings to dateDuring the study period, the number of cases of acute pancreatitis in Sweden has more than doubled from 1977 cases in 1990 to 4264 cases in 2019. The median age of first episode of acute pancreatitis has increased from 58 years (IQR 44–73 years) in 1990 to 64 years (IQR 49–76 years) in 2019. Cases with acute pancreatitis were generally less healthy compared with the pancreatitis-free individuals (Charlson Comorbidity Index of 0 in 59.2% and 71.4%, respectively).Future plansSwePan will be used to determine the incidence of acute pancreatitis in Sweden over time and assess long-term all-cause and cause-specific mortality after an episode of acute pancreatitis. Some examples of additional planned studies are (1) assessment of long-term risk of diabetes and (2) risk of malignancy in adjacent organs following acute pancreatitis and (3) assessment of risk factors for development of acute pancreatitis including various drugs.

Background Acute pancreatitis is a potentially life‐threatening inflammation of the pancreas, with a rising incidence in most countries. Recent studies have suggested that acute pancreatitis is associated with increased long‐term mortality. However, the extent to which this association is influenced by the development of chronic pancreatitis or comorbid conditions, such as malignant disease, remains unclear. Objective To assess the association between acute pancreatitis and long‐term all‐cause mortality. Methods The Swedish Pancreatitis Cohort (SwePan) was used, including all individuals with a first‐time episode of acute pancreatitis in Sweden between 1990 and 2019 who survived the index hospital stay and 1:10 matched pancreatitis‐free individuals from the general population. Multivariable conditional Cox proportional hazard models were used to compare mortality among individuals with acute pancreatitis compared with the matched pancreatitis‐free control group. Results In total, 89,465 individuals discharged from hospital with acute pancreatitis and 890,837 matched pancreatitis‐free individuals were followed up for 10,155,039 person‐years (mean 10.0 years). There were 33,764 (37.7%) deaths among individuals with acute pancreatitis and 265,403 (29.8%) deaths among controls. In multivariable adjusted models, mortality was increased in individuals with acute pancreatitis throughout the follow‐up period, particularly among those with severe and non‐gallstone‐related acute pancreatitis as compared to the matched controls. These results remained statistically significant after censoring the follow‐up time for recurrent acute pancreatitis or a diagnosis of chronic pancreatitis. Conclusions Acute pancreatitis was associated with increased long‐term mortality, even after adjusting for comorbidities, including cancer, and censoring for recurrent acute pancreatitis or chronic pancreatitis. Future research should assess causes of death and focus on understanding long‐term morbidity to facilitate prevention through tailored follow‐up strategies.

Background Biliary tract cancer (BTC) often goes undetected until its advanced stages, resulting in a poor prognosis. Given the anatomical closeness of the gallbladder and bile ducts to the pancreas, the inflammatory processes triggered by acute pancreatitis might increase the risk of BTC. Objective To assess the association between acute pancreatitis and the risk of BTC. Methods Using the Swedish Pancreatitis Cohort (SwePan), we compared the BTC risk in patients with a first‐time episode of acute pancreatitis during 1990–2018 to a 1:10 matched pancreatitis‐free control group. Multivariable Cox regression models, stratified by follow‐up duration, were used to calculate hazard ratios (HRs), adjusting for socioeconomic factors, alcohol use, and comorbidities. Results BTC developed in 0.94% of 85,027 acute pancreatitis patients and in 0.23% of 814,993 controls. The BTC risk notably increased within 3 months of hospital discharge (HR 82.63; 95% CI: 63.07–108.26) and remained elevated beyond 10 years of follow‐up (HR 1.82; 95% CI: 1.35–2.47). However, the long‐term risk of BTC subtypes did not increase with anatomical proximity to the pancreas, with a null association for gallbladder and extrahepatic tumors. Importantly, patients with acute pancreatitis had a higher occurrence of early‐stage BTC within 2 years of hospital discharge than controls (13.0 vs. 3.6%; p‐value <0.01). Conclusion Our nationwide study found an elevated BTC risk in acute pancreatitis patients; however, the risk estimates for BTC subtypes were inconsistent, thereby questioning the causality of the association. Importantly, the amplified detection of early‐stage BTC within 2 years after a diagnosis of acute pancreatitis underscores the necessity for proactive BTC surveillance in these patients.

We review recent progress in our understanding of the global cycling of mercury (Hg), including best estimates of Hg concentrations and pool sizes in major environmental compartments and exchange processes within and between these reservoirs. Recent advances include the availability of new global datasets covering areas of the world where environmental Hg data were previously lacking; integration of these data into global and regional models is continually improving estimates of global Hg cycling. New analytical techniques, such as Hg stable isotope characterization, provide novel constraints of sources and transformation processes. The major global Hg reservoirs that are, and continue to be, affected by anthropogenic activities include the atmosphere (4.4–5.3 Gt), terrestrial environments (particularly soils: 250–1000 Gg), and aquatic ecosystems (e.g., oceans: 270–450 Gg). Declines in anthropogenic Hg emissions between 1990 and 2010 have led to declines in atmospheric Hg 0 concentrations and Hg II wet deposition in Europe and the US (− 1.5 to − 2.2% per year). Smaller atmospheric Hg 0 declines (− 0.2% per year) have been reported in high northern latitudes, but not in the southern hemisphere, while increasing atmospheric Hg loads are still reported in East Asia. New observations and updated models now suggest high concentrations of oxidized Hg II in the tropical and subtropical free troposphere where deep convection can scavenge these Hg II reservoirs. As a result, up to 50% of total global wet Hg II deposition has been predicted to occur to tropical oceans. Ocean Hg 0 evasion is a large source of present-day atmospheric Hg (approximately 2900 Mg/year; range 1900–4200 Mg/year). Enhanced seawater Hg 0 levels suggest enhanced Hg 0 ocean evasion in the intertropical convergence zone, which may be linked to high Hg II deposition. Estimates of gaseous Hg 0 emissions to the atmosphere over land, long considered a critical Hg source, have been revised downward, and most terrestrial environments now are considered net sinks of atmospheric Hg due to substantial Hg uptake by plants. Litterfall deposition by plants is now estimated at 1020–1230 Mg/year globally. Stable isotope analysis and direct flux measurements provide evidence that in many ecosystems Hg 0 deposition via plant inputs dominates, accounting for 57–94% of Hg in soils. Of global aquatic Hg releases, around 50% are estimated to occur in China and India, where Hg drains into the West Pacific and North Indian Oceans. A first inventory of global freshwater Hg suggests that inland freshwater Hg releases may be dominated by artisanal and small-scale gold mining (ASGM; approximately 880 Mg/year), industrial and wastewater releases (220 Mg/year), and terrestrial mobilization (170–300 Mg/year). For pelagic ocean regions, the dominant source of Hg is atmospheric deposition; an exception is the Arctic Ocean, where riverine and coastal erosion is likely the dominant source. Ocean water Hg concentrations in the North Atlantic appear to have declined during the last several decades but have increased since the mid-1980s in the Pacific due to enhanced atmospheric deposition from the Asian continent. Finally, we provide examples of ongoing and anticipated changes in Hg cycling due to emission, climate, and land use changes. It is anticipated that future emissions changes will be strongly dependent on ASGM, as well as energy use scenarios and technology requirements implemented under the Minamata Convention. We predict that land use and climate change impacts on Hg cycling will be large and inherently linked to changes in ecosystem function and global atmospheric and ocean circulations. Our ability to predict multiple and simultaneous changes in future Hg global cycling and human exposure is rapidly developing but requires further enhancement.

Mycoviruses generally contain dsRNA genomes but ssRNA and ssDNA examples are known. Mycovirus diversity is increasing, and here we describe a unique example that contains four dsRNA elements nominated Aspergillus fumigatus tetramycovirus-1 (AfuTmV-1). We show for the first time (to our knowledge) that both purified AfuTmV-1 and its dsRNA are infectious for protoplasts and that the virus genome is not conventionally encapsidated and has a unique organization. Separation of the genes encoding the RNA-dependent RNA polymerase enzyme responsible for copying the viral genome and an S -adenosyl methionine-dependent methyltransferase capping enzyme on different dsRNAs is also previously unreported for a mycovirus. AfuTmV-1 appears to be intermediate between dsRNA and positive-strand ssRNA viruses, as well as between encapsidated and capsidless RNA viruses. We report the discovery and characterization of a double-stranded RNA (dsRNA) mycovirus isolated from the human pathogenic fungus Aspergillus fumigatus , Aspergillus fumigatus tetramycovirus-1 (AfuTmV-1), which reveals several unique features not found previously in positive-strand RNA viruses, including the fact that it represents the first dsRNA (to our knowledge) that is not only infectious as a purified entity but also as a naked dsRNA. The AfuTmV-1 genome consists of four capped dsRNAs, the largest of which encodes an RNA-dependent RNA polymerase (RdRP) containing a unique GDNQ motif normally characteristic of negative-strand RNA viruses. The third largest dsRNA encodes an S -adenosyl methionine–dependent methyltransferase capping enzyme and the smallest dsRNA a P-A-S–rich protein that apparently coats but does not encapsidate the viral genome as visualized by atomic force microscopy. A combination of a capping enzyme with a picorna-like RdRP in the AfuTmV-1 genome is a striking case of chimerism and the first example (to our knowledge) of such a phenomenon. AfuTmV-1 appears to be intermediate between dsRNA and positive-strand ssRNA viruses, as well as between encapsidated and capsidless RNA viruses.

While the advances in synchrotron light sources, together with the development of focusing optics and detectors, allow nanoscale ptychographic imaging of materials and biological specimens, the corresponding experiments can yield terabyte-scale volumes of data that can impose a heavy burden on the computing platform. Although graphics processing units (GPUs) provide high performance for such large-scale ptychography datasets, a single GPU is typically insufficient for analysis and reconstruction. Several works have considered leveraging multiple GPUs to accelerate the ptychographic reconstruction. However, most of these works utilize only the Message Passing Interface to handle the communications between GPUs. This approach poses inefficiency for a hardware configuration that has multiple GPUs in a single node, especially while reconstructing a single large projection, since it provides no optimizations to handle the heterogeneous GPU interconnections containing both low-speed (e.g., PCIe) and high-speed links (e.g., NVLink). In this paper, we provide an optimized intranode multi-GPU implementation that can efficiently solve large-scale ptychographic reconstruction problems. We focus on the maximum likelihood reconstruction problem using a conjugate gradient (CG) method for the solution and propose a novel hybrid parallelization model to address the performance bottlenecks in the CG solver. Accordingly, we have developed a tool, called PtyGer ( Pty chographic G PU(multipl e )-based r econstruction), implementing our hybrid parallelization model design. A comprehensive evaluation verifies that PtyGer can fully preserve the original algorithm’s accuracy while achieving outstanding intranode GPU scalability.

Proximate composition (moisture, protein, lipid and ash content) and nutritional value (fatty acid, amino acid and mineral profile) of three macroalgae (Ascophyllum nodosum, Fucus vesiculosus and Bifurcaria bifurcate) were studied. Chemical composition was significantly (p < 0.001) different among the three seaweeds. In this regard, the B. bifurcata presented the highest fat content (6.54% of dry matter); whereas, F. vesiculosus showed the highest protein level (12.99% dry matter). Regarding fatty acid content, the polyunsaturated fatty acids (PUFAs) were the most abundant followed by saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). On the other hand, the three seaweeds are a rich source of K (from 3781.35 to 9316.28 mg/100 g), Mn (from 8.28 to 1.96 mg/100 g), Na (from 1836.82 to 4575.71 mg/100 g) and Ca (from 984.73 to 1160.27 mg/100 g). Finally, the most abundant amino acid was glutamic acid (1874.47–1504.53 mg/100 dry matter), followed by aspartic acid (1677.01–800.84 mg/100 g dry matter) and alanine (985.40–655.73 mg/100 g dry matter).

The cytokine IFNγ differentially impacts on tumors upon immune checkpoint blockade (ICB). Despite our understanding of downstream signaling events, less is known about regulation of its receptor (IFNγ-R1). With an unbiased genome-wide CRISPR/Cas9 screen for critical regulators of IFNγ-R1 cell surface abundance, we identify STUB1 as an E3 ubiquitin ligase for IFNγ-R1 in complex with its signal-relaying kinase JAK1. STUB1 mediates ubiquitination-dependent proteasomal degradation of IFNγ-R1/JAK1 complex through IFNγ-R1 K285 and JAK1 K249 . Conversely, STUB1 inactivation amplifies IFNγ signaling, sensitizing tumor cells to cytotoxic T cells in vitro. This is corroborated by an anticorrelation between STUB1 expression and IFNγ response in ICB-treated patients. Consistent with the context-dependent effects of IFNγ in vivo, anti-PD-1 response is increased in heterogenous tumors comprising both wildtype and STUB1-deficient cells, but not full STUB1 knockout tumors. These results uncover STUB1 as a critical regulator of IFNγ-R1, and highlight the context-dependency of STUB1-regulated IFNγ signaling for ICB outcome. The IFNγ response pathway is associated with response to immunotherapy in cancer. Here the authors show that high levels of the IFNγ-receptor (IFNγ-R1) affect the outcome of immunotherapy in a context-dependent fashion and identify the E3 ubiquitin ligase STUB1 as a negative regulator of IFNγ-R1/JAK1 expression in cancer cells.

State and local policy-makers in the US have shown interest in transitioning electricity systems toward renewable energy sources and in mitigating harmful air pollution. However, the extent to which sub-national renewable energy policies can improve air quality remains unclear. To investigate this issue, we develop a systemic modeling framework that combines economic and air pollution models to assess the projected sub-national impacts of Renewable Portfolio Standards (RPSs) on air quality and human health, as well as on the economy and on climate change. We contribute to existing RPS cost-benefit literature by providing a comprehensive assessment of economic costs and estimating economy-wide changes in emissions and their impacts, using a general equilibrium modeling approach. This study is also the first to our knowledge to directly compare the health co-benefits of RPSs to those of carbon pricing. We estimate that existing RPSs in the 'Rust Belt' region generate a health co-benefit of $94 per ton CO2 reduced ($2-477/tCO2) in 2030, or 8¢ for each kWh of renewable energy deployed (0.2-40¢ kWh−1) in 2015 dollars. Our central estimate is 34% larger than total policy costs. We estimate that the central marginal benefit of raising renewable energy requirements exceeds the marginal cost, suggesting that strengthening RPSs increases net societal benefits. We also calculate that carbon pricing delivers health co-benefits of $211/tCO2 in 2030, 63% greater than the health co-benefit of reducing the same amount of CO2 through an RPS approach.

Gender is one of the central categories organizing children’s social world. Clear patterns of gender development have been well-documented among cisgender children (i.e., children who identify as a gender that is typically associated with their sex assigned at birth). We present a comprehensive study of gender development (e.g., gender identity and gender expression) in a cohort of 3- to 12-y-old transgender children (n = 317) who, in early childhood, are identifying and living as a gender different from their assigned sex. Four primary findings emerged. First, transgender children strongly identify as members of their current gender group and show gender-typed preferences and behaviors that are strongly associated with their current gender, not the gender typically associated with their sex assigned at birth. Second, transgender children’s gender identity (i.e., the gender they feel they are) and gender-typed preferences generally did not differ from 2 comparison groups: cisgender siblings (n = 189) and cisgender controls (n = 316). Third, transgender and cisgender children’s patterns of gender development showed coherence across measures. Finally, we observed minimal or no differences in gender identity or preferences as a function of how long transgender children had lived as their current gender. Our findings suggest that early sex assignment and parental rearing based on that sex assignment do not always define how a child identifies or expresses gender later.