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"Roth, Jonathan"
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This planet rocks!
Two mismatched rovers alone on a distant planet - what could possibly go wrong? When Rover crash-lands on a rocky planet and finds Speck stranded and in need of a battery charge, the two hardly seem destined to be teammates. Rover: organized, careful and on a mission to explore the galaxy. Speck: impulsive, excitable and not sure what his mission is. Their differences are forgotten, however, when they make their first discovery: they're not alone! And suddenly their only mission is to escape from the rock creatures that are chasing them!
CHILDBOOK
Pretest with Caution
This paper discusses two important limitations of the common practice of testing for preexisting differences in trends (“pre-trends”) when using difference-in-differences and related methods. First, conventional pre-trends tests may have low power. Second, conditioning the analysis on the result of a pretest can distort estimation and inference, potentially exacerbating the bias of point estimates and under-coverage of confidence intervals. I analyze these issues both in theory and in simulations calibrated to a survey of recent papers in leading economics journals, which suggest that these limitations are important in practice. I conclude with practical recommendations for mitigating these issues.
Journal Article
Double trouble
While working on his duplication ray, Bob accidentally makes clones of himself and his alien friend Beep, and soon finds out that their doubles are evil and plan to rule the Earth.
Book
Increased hepatoprotective effects of the novel farnesoid X receptor agonist INT-787 versus obeticholic acid in a mouse model of nonalcoholic steatohepatitis
The nuclear farnesoid X receptor (FXR), a master regulator of bile acid and metabolic homeostasis, is a key target for treatment of nonalcoholic steatohepatitis (NASH). This study compared efficacy of FXR agonists obeticholic acid (OCA) and INT-787 by liver histopathology, plasma biomarkers of liver damage, and hepatic gene expression profiles in the Amylin liver NASH (AMLN) diet–induced and biopsy-confirmed Lep ob/ob mouse model of NASH. Lep ob/ob mice were fed the AMLN diet for 12 weeks before liver biopsy and subsequent treatment with vehicle, OCA, or INT-787 for 8 weeks. Hepatic steatosis, inflammation, and fibrosis (liver lipids, galectin-3, and collagen 1a1 [Col1a1], respectively), as well as plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, were assessed. Hepatic gene expression was assessed in Lep ob/ob mice that were fed the AMLN diet for 14 weeks then treated with vehicle, OCA, or INT-787 for 2 weeks. INT-787, which is equipotent to OCA but more hydrophilic, significantly reduced liver lipids, galectin-3, and Col1a1 compared with vehicle, and to a greater extent than OCA. INT-787 significantly reduced plasma ALT and AST levels, whereas OCA did not. INT-787 modulated a substantially greater number of genes associated with FXR signaling, lipid metabolism, and stellate cell activation relative to OCA in hepatic tissue. These findings demonstrate greater efficacy of INT-787 treatment compared with OCA in improving liver histopathology, decreasing liver enzyme levels, and enhancing gene regulation, suggesting superior clinical potential of INT-787 for the treatment of NASH and other chronic liver diseases.
Journal Article
Party crashers
Beep and his best friend, Bob, are accused of stealing guests' jewelry during Lani's birthday voyage on luxurious Starship Titanic, but things go downhill when Titanic plummets toward Neptune. Includes facts about Neptune.
Book
Precision mutational scanning: your multipass to the future of genetics
Massively parallel base and prime editing screens provide unparalleled interrogation of genetic variants with single-nucleotide resolution.
Journal Article
Too much space!
After being humiliated while on a field trip to Pluto, Bob, with the help of his alien friend Beep, tries to change his personality and overcome his fears (heights, darkness, space, and spiders) before the next field trip to a black hole. Includes facts about Pluto.
Book
Predictors of shunt responsiveness and outcomes in idiopathic normal pressure hydrocephalus: a retrospective cohort study
Background
Idiopathic Normal Pressure Hydrocephalus (iNPH) remains a challenging clinical diagnosis with variable treatment response.
Objectives
This study aimed to identify clinical, imaging, and CSF biomarkers associated with favorable outcomes following shunt placement.
Methods
All patients evaluated for iNPH at the Tel-Aviv Medical Center (TLVMC) between 2020 and 2022 were included. Participants underwent clinical, cognitive, and imaging assessments, high-volume lumbar puncture (LP). LP responders were referred for shunt placement, and outcomes assessed at one year.
Results
183 patients were evaluated; 167 met criteria for suspected iNPH and underwent LP. Sixty-two (37%) patients showed improvement after CSF drainage and were referred for shunting. Of these, 38 (61%) underwent shunt placement. Gait disturbance was the most common presenting symptom (68%), and more frequent in LP responders (
p
= 0.007), whereas cognitive symptoms were more common among non-responders (29.5% vs. 10%). LP responders had lower CSF total tau (t-tau) (222.6 ± 99.1 vs. 256 ± 107.1,
p
= 0.045) and protein (41.1 ± 17.1 vs. 49.1 ± 25.7,
p
= 0.032) and were more likely to exhibit a disproportionately enlarged subarachnoid-space hydrocephalus (DESH) pattern (73% vs. 46%,
p
< 0.001). Among the 38 shunted patients, 21 (55%) had a favourable outcome at one year, which was associated with lower t-tau (
p
= 0.056) and more frequent DESH (
p
= 0.026).
Conclusions
Over half of patients who underwent shunt placement experienced favorable clinical outcomes at one year. Lower t-tau and DESH pattern were associated with better outcomes.
Journal Article
Design of synthetic collagens that assemble into supramolecular banded fibers as a functional biomaterial testbed
Collagens are the most abundant proteins of the extracellular matrix, and the hierarchical folding and supramolecular assembly of collagens into banded fibers is essential for mediating cell-matrix interactions and tissue mechanics. Collagen extracted from animal tissues is a valuable commodity, but suffers from safety and purity issues, limiting its biomaterials applications. Synthetic collagen biomaterials could address these issues, but their construction requires molecular-level control of folding and supramolecular assembly into ordered banded fibers, comparable to those of natural collagens. Here, we show an innovative class of banded fiber-forming synthetic collagens that recapitulate the morphology and some biological properties of natural collagens. The synthetic collagens comprise a functional-driver module that is flanked by adhesive modules that effectively promote their supramolecular assembly. Multiscale simulations support a plausible molecular-level mechanism of supramolecular assembly, allowing precise design of banded fiber morphology. We also experimentally demonstrate that synthetic fibers stimulate osteoblast differentiation at levels comparable to natural collagen. This work thus deepens understanding of collagen biology and disease by providing a ready source of safe, functional biomaterials that bridge the current gap between the simplicity of peptide biophysical models and the complexity of in vivo animal systems.
Journal Article