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The Delta variant of SARS-CoV-2, first identified in India in October 2020 (1), became the dominant variant in [greater than or equal to] 130 countries worldwide during June-November 2021 (2). [...]

When encountering objects, we readily perceive not only low-level properties (e.g., color and orientation), but also seemingly higher-level ones--including aspects of physics (e.g., mass). Perhaps nowhere is this contrast more salient than in the perception of soft materials such as cloths: the dynamics of these objects (including how their three-dimensional forms vary) are determined by their physical properties such as stiffness, elasticity, and mass. Here we hypothesize that the perception of cloths and their physical properties must involve not only image statistics, but also abstract object representations that incorporate "intuitive physics". We provide behavioral and computational evidence for this hypothesis. We find that humans can visually match the stiffness of cloths with unfamiliar textures from the way they undergo natural transformations (e.g. flapping in the wind) across different scenarios. A computational model that casts cloth perception as mental physics simulation explains important aspects of this behavior. Full paper can be found at https://www.biorxiv.org/content/10.1101/2021.05.12.443806v1.

Type 2 diabetes is clinically associated with progressive necroinflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Advanced glycation end-products (AGEs) accumulate during prolonged hyperglycemia, but the mechanistic pathways that lead to accelerated liver fibrosis have not been well defined. In this study, we show that the AGEs clearance receptor AGER1 was downregulated in patients with NASH and diabetes and in our NASH models, whereas the proinflammatory receptor RAGE was induced. These findings were associated with necroinflammatory, fibrogenic, and pro-oxidant activity via the NADPH oxidase 4. Inhibition of AGEs or RAGE deletion in hepatocytes in vivo reversed these effects. We demonstrate that dysregulation of NRF2 by neddylation of cullin 3 was linked to AGER1 downregulation and that induction of NRF2 using an adeno-associated virus-mediated approach in hepatocytes in vivo reversed AGER1 downregulation, lowered the level of AGEs, and improved proinflammatory and fibrogenic responses in mice on a high AGEs diet. In patients with NASH and diabetes or insulin resistance, low AGER1 levels were associated with hepatocyte ballooning degeneration and ductular reaction. Collectively, prolonged exposure to AGEs in the liver promotes an AGER1/RAGE imbalance and consequent redox, inflammatory, and fibrogenic activity in NASH.

Total oil and grease (TOG) in water is measured in industrial process waters to determine the concentration of petroleum products present. A common application for TOG measurement is to detect a hydrocarbon leak in circulated cooling water systems. A hydrocarbon leak from a heat exchanger has a negative effect on the stable operation of upgrading and refinery units. Detecting and quantifying a hydrocarbon leak is straightforward; however, identifying the source of the leak can be very time consuming and require a lot of trial and error. In this study, a solvent‐free TOG method using ClearShot extractors and Fourier transform infrared spectroscopy (FTIR) was developed and optimized for the quantification of bitumen derived hydrocarbon analytes in water. This was further expanded upon to develop a rapid method for hydrocarbon identification in the cooling water by combining chemical fingerprinting with a discriminant analysis classification model. Following the optimized solvent‐free TOG method, chemical fingerprints for six different hydrocarbon classes in water were analyzed by FTIR. The classification model for these hydrocarbon classes was constructed using a discriminant analysis algorithm with a 100% classification rate at a TOG mass loading greater than 150 μg. The optimized solvent‐free TOG method decreases exposure risk and ergonomic strain for technologists, improving overall safety and environmental performance. The hydrocarbon fingerprinting enables rapid prediction of a leak source which reduces the time and analysis required to isolate a leak as well as reducing the cost and environmental impact associated with blowdown and purge (disposal and treatment) of contaminated water. [ABSTRACT FROM AUTHOR]

Abdominal ascites is most commonly caused by portal hypertension from liver cirrhosis. When present, portal hypertension is associated with an elevated serum-ascites albumin gradient (SAAG) ≥1.1 g/dL. In contrast, a SAAG < 1.1 g/dL suggests malignancy, tuberculosis, pancreatitis, or nephrotic syndrome. Here, we present a case of low SAAG ascites caused by epithelioid peritoneal mesothelioma in a woman with no known liver disease. The diagnosis proved elusive until diagnostic laparoscopy with biopsy was performed.

BackgroundAn exploratory study was performed to determine the prevalence of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs78409 [G] allele among the Hmong as a risk factor for nonalcoholic fatty liver disease (NAFLD). NAFLD/nonalcoholic steatohepatitis is the world's most common chronic liver disease and is expected to replace viral hepatitis as the leading cause of cirrhosis and potential precursor to hepatocellular carcinoma (HCC). Of all populations in California, the Hmong experience the highest risk of death from HCC and the highest prevalence of metabolic syndrome risk factors among Asians that predispose them to NAFLD. Here a genetic explanation was sought for the high rates of chronic liver disease among the Hmong. The literature pointed to the PNPLA3 rs738409 [G] allele as a potential genetic culprit.MethodsCell-free DNA was isolated from 26 serum samples previously collected in community settings. Quantitative polymerase chain reaction-based single-nucleotide polymorphism (SNP) genotyping was performed with a validated TaqMan SNP genotyping assay, and results were analyzed with TaqMan Genotyper software.ResultsThe PNPLA3 rs738409 [C>G] variant occurred at a frequency of 0.46 (12 of 26; 95% confidence interval, 0.27-0.67). This carrier rate would rank the Hmong as the third highest population in the 1000 Genomes Project.ConclusionsAlthough this small sample size limits the generalizability, the high frequency rates of this allele along with the presence of metabolic syndrome risk factors warrant further studies into the etiology of NAFLD among the Hmong. Cancer 2018;124:1583-9. © 2018 American Cancer Society.

Primary biliary cholangitis (PBC) is an autoimmune inflammatory liver disease of the interlobular bile ducts that can lead to cirrhosis and liver failure. Until recently, the only effective treatment was ursodeoxycholic acid (UDCA). However, up to 40% of PBC patients have an inadequate response to UDCA and may continue to have disease progression. Several models have been developed, including the UK-PBC and GLOBE scores, to assist in identifying patients who may benefit from second-line therapies, such as the farnesoid X receptor (FXR) agonist obeticholic acid (OCA). The addition of OCA can significantly improve serum alkaline phosphatase and total bilirubin, which are strong surrogate markers of clinical outcomes in PBC. Other alternatives, including the peroxisome proliferator-activated receptor (PPAR)-α agonists fenofibrate and bezafibrate, may also improve liver biochemistries in PBC patients with an inadequate response to UDCA, but further study is needed to demonstrate their safety and long-term efficacy. Other novel agents, including those targeting the FXR pathway and PPAR-δ agonists, have shown promising results and may alter the therapeutic landscape of PBC in the near future. For now, OCA remains the only approved second-line agent for PBC patients with an inadequate response to UDCA while results of long-term studies of its safety and clinical benefit are awaited.

Background & aimsThe hepatocyte-derived hormone fibroblast growth factor 21 (FGF21) is a hormone-like regulator of metabolism. The nicotinamide adenine dinucleotide-dependent deacetylase SIRT1 regulates fatty acid metabolism through multiple nutrient sensors. Hepatic overexpression of SIRT1 reduces steatosis and glucose intolerance in obese mice. We investigated mechanisms by which SIRT1 controls hepatic steatosis in mice.MethodsLiver-specific SIRT1 knockout (SIRT1 LKO) mice and their wild-type littermates (controls) were divided into groups that were placed on a normal chow diet, fasted for 24 hours, or fasted for 24 hours and then fed for 6 hours. Liver tissues were collected and analyzed by histologic examination, gene expression profiling, and real-time polymerase chain reaction assays. Human HepG2 cells were incubated with pharmacologic activators of SIRT1 (resveratrol or SRT1720) and mitochondrion oxidation consumption rate and immunoblot analyses were performed. FGF21 was overexpressed in SIRT1 LKO mice using an adenoviral vector. Energy expenditure was assessed by indirect calorimetry.ResultsProlonged fasting induced lipid deposition in livers of control mice, but severe hepatic steatosis in SIRT1 LKO mice. Gene expression analysis showed that fasting up-regulated FGF21 in livers of control mice but not in SIRT1 LKO mice. Decreased hepatic and circulating levels of FGF21 in fasted SIRT1 LKO mice were associated with reduced hepatic expression of genes involved in fatty acid oxidation and ketogenesis, and increased expression of genes that control lipogenesis, compared with fasted control mice. Resveratrol or SRT1720 each increased the transcriptional activity of the FGF21 promoter (-2070/+117) and levels of FGF21 messenger RNA and protein in HepG2 cells. Surprisingly, SIRT1 LKO mice developed late-onset obesity with impaired whole-body energy expenditure. Hepatic overexpression of FGF21 in SIRT1 LKO mice increased the expression of genes that regulate fatty acid oxidation, decreased fasting-induced steatosis, reduced obesity, increased energy expenditure, and promoted browning of white adipose tissue.ConclusionsSIRT1-mediated activation of FGF21 prevents liver steatosis caused by fasting. This hepatocyte-derived endocrine signaling appears to regulate expression of genes that control a brown fat-like program in white adipose tissue, energy expenditure, and adiposity. Strategies to activate SIRT1 or FGF21 could be used to treat fatty liver disease and obesity.

Summary: Mantle cell lymphoma (MCL) is a B‐cell non‐Hodgkin lymphoma characterised by a heterogeneous clinical course. Patients can often receive sequential treatments, yet these typically yield diminishing periods of disease control, raising questions about optimal therapy sequencing. Novel agents, such as chimeric antigen receptor T‐cell therapies and bispecific antibodies, show promise in relapsed MCL, but are often reserved for later treatment lines, which may underserve patients with aggressive disease phenotypes who die early in the treatment journey. To assess the problem of patient attrition from lymphoma‐related death limiting sequential treatment, we performed a multicentre retrospective cohort analysis of 389 patients treated at Australian and UK centres over a 10‐year period. Deaths from MCL increased after each treatment line, with 7%, 23% and 26% of patients dying from uncontrolled MCL after first, second and third lines respectively. Patients with older age at diagnosis and early relapse after induction therapy were at particular risk of death after second‐line treatment. This limitation of sequential treatment by lymphoma‐related death provides support for the trial of novel therapies in earlier treatment lines, particularly in high‐risk patient populations. [ABSTRACT FROM AUTHOR]

Our experience of time is strikingly plastic: Depending on contextual factors, the same objective duration can seem to fly by or drag on. Perhaps the most direct demonstration of such subjective time dilation is the oddball effect: when seeing identical objects appear one after another, followed by an "oddball" (e.g., a disc that suddenly grows in size, in a sequence of otherwise static discs), observers experience this oddball as having lasted longer than its nonoddball counterparts. Despite extensive work on this phenomenon, a surprisingly foundational question remains unasked: What actually gets dilated? Beyond the oddball, are the objects just before (or just after) the oddball also dilated? As in previous studies, observers viewed sequences of colored discs, one of which could be the oddball—and subsequently reproduced the oddball's duration. Unlike previous studies, however, there were also critical trials in which observers instead reproduced the duration of the disc immediately before or after the oddball. A clear pattern emerged: oddball-induced time dilation extended to the post-oddball disc, but not the pre-oddball disc. Whence this temporal asymmetry? We suggest that an oddball's sudden appearance may induce uncertainty about what will happen next, heightening attention until after the uncertainty is resolved. [ABSTRACT FROM AUTHOR]

The CORFIS ("Community-Based Cardiovascular Risk Factors Intervention Strategies") program was piloted in community clinics in Malaysia to address the lack of health education in chronic disease management. The stages of change model was applied in a multicenter quasi-experimental design to evaluate adherence to advocated behaviors in CORFIS patients with hypertension. Based on submitted diet and exercise records (n = 209), adherence to sodium reduction, regular exercise, and increasing fruit and vegetable intake behaviors were quantified against weight, waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) changes. Patients were categorized at 6 months into nonadherent/N-A (Precontemplation, Contemplation, and Preparation), newly adherent/NA (Action) and totally adherent/TA (Maintenance) groups. Self-reported adherence records did not meet recommended targets for healthful behaviors, but clinical benefits were achieved by adherent groups as indicated by effect size (Cohen's d) comparisons. SBP reduction was associated with adherence to sodium reduction in NA (d = 0.60, p < 0.001) and TA (d = 0.45, p < 0.001) compared to N-A (d = 0.13, p > 0.05). Marginally increasing fruit and vegetable consumption (? = 0.41 servings) resulted in sizeable reductions in weight for NA (d = 0.81, p < 0.001) > TA (d = 0.54, p < 0.001) > N-A (d = 0.21, p > 0.05) and in WC for NA (d = 0.68, p < 0.00) > TA (d = 0.53, p < 0.001) > N-A (d = 0.52, p > 0.05). Exercise behavior was least successful as pedometer counting was below 10,000 steps but sizeable weight and WC reductions were largest for NA (d = 0.71 and 0.79, respectively) > TA (d = 0.60 and 0.53, respectively) > N-A (d = 0.33 and 0.35, respectively). Patients reporting a shift to positive stages of change behaviors enjoyed clinically beneficial reductions in SBP, DBP, weight, and WC.

Background: Universal leucocyte depletion reduces the risk of transfusion‐transmitted cytomegalovirus; however, many clinicians still prescribe cytomegalovirus seronegative units. Aim: Our retrospective study aims to confirm the low risk of transfusion‐transmitted cytomegalovirus with leucocyte depletion alone and demonstrate the ongoing variability in cytomegalovirus seronegative transfusion prescribing. Methods: Over a 9‐year period (July 2009–July 2018), occurrences of transfusion transmitted cytomegalovirus in cytomegalovirus seronegative donor/recipient haemopoietic stem cell transplant pairs were compared at one allogeneic haemopoietic stem cell transplant centre providing cytomegalovirus seronegative blood products and leucocyte depletion (double prevention) versus another providing leucocyte depletion only (single prevention). Retrospective chart audit identified patient demographics, blood product exposure and cytomegalovirus infection by polymerase chain reaction. A separate audit examined cytomegalovirus seronegative blood product ordering in a broader range of hospital types. Results: We identified 122 and 66 cytomegalovirus‐negative donor/recipient haemopoietic stem cell transplant pairs using double and single transfusion prevention strategy respectively. Transfusion exposure to red cells and pooled platelets was similar, although more apheresis platelets were used in the double prevention group. The cytomegalovirus infection rate was 3 (2.4%) and zero in the double and single prevention groups respectively. Cytomegalovirus seronegative unit ordering was not limited to hospitals with obstetric or neonatal populations, suggesting ongoing reliance of cytomegalovirus seronegative units outside this population. Conclusions: The analysis suggests a double prevention strategy does not provide additional protection against transfusion‐transmitted cytomegalovirus. There is ongoing variability in the acceptance of leucocyte depletion alone despite the low risk of cytomegalovirus infection. [ABSTRACT FROM AUTHOR]

Due to cultural and linguistic barriers, as well as a fear of deportation, undocumented immigrant students have remained an invisible group face in the existing school system. We provide specific strategies for school counselors to consider in advocating social justice and in facilitating empowerment of undocumented immigrant students through group work. A case vignette is presented to highlight challenges confronting undocumented immigrants and to offer strategies for school counselors as specialists in group work to address the unique educational and psychological needs of undocumented immigrant students.

We typically think of intuitive physics in terms of high-level cognition, but might aspects of physics also be extracted during lower-level visual processing? Might we not only think about physics, but also see it? We explored this using multiple tasks in online adult samples with objects covered by soft materials—as when you see a chair with a blanket draped over it—where you must account for the physical interactions between cloth, gravity, and object. In multiple change-detection experiments (n = 200), observers from an online testing marketplace were better at detecting image changes involving underlying object structure versus those involving only the superficial folds of cloths—even when the latter were more extreme along several dimensions. And in probe-comparison experiments (n = 100), performance was worse when both probes (vs. only one) appeared on image regions reflective of underlying object structure (equating visual properties). This work collectively shows how vision uses intuitive physics to recover the deeper underlying structure of scenes. [ABSTRACT FROM AUTHOR]