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New complex physiological findings evolve hypothesized mechanisms of Dravet syndrome

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Neural Regeneration Research 2024年第9期19卷 1867-1868页

作者： MacKenzie A.howard Department of Neurology Dell Medical SchoolAustinTXUSA Center for Learning and Memory and Department of Neuroscience University of Texas at AustinAustinTXUSA

Developmental and epileptic encephalopathies(DEEs)are neurological disorders generally involving medically intractable seizures and a diverse array of comorbid neuropsychiatric delays and deficits that may severely affect cognition,mood,sleep,social behavior,movement control,learning,and/or *** syndrome(DS),also known as Severe Myoclonic Epilepsy of Infancy.

关键词： sized finding seizures

Global Solutions to Nonconvex Problems by Evolution of Hamilton-Jacobi PDEs

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Communications on Applied Mathematics and Computation 2024年第2期6卷 790-810页

作者： howard Heaton Samy Wu Fung Stanley Osher Typal Research Typal LLCLos AngelesUSA Department of Applied Mathematics and Statistics Colorado School of MinesGoldenUSA Department Mathematics UCLALos AngelesUSA

Computing tasks may often be posed as optimization *** objective functions for real-world scenarios are often nonconvex and/or ***-of-the-art methods for solving these problems typically only guarantee convergence to local *** work presents Hamilton-Jacobi-based Moreau adaptive descent(HJ-MAD),a zero-order algorithm with guaranteed convergence to global minima,assuming continuity of the objective *** core idea is to compute gradients of the Moreau envelope of the objective(which is"piece-wise convex")with adaptive smoothing *** of the Moreau envelope(i.e.,proximal operators)are approximated via the Hopf-Lax formula for the viscous Hamilton-Jacobi *** numerical examples illustrate global convergence.

关键词： Global optimization Moreau envelope Hamilton-Jacobi Hopf-Lax-Cole-Hopf Proximals Zero-order optimization

Gastroesophageal reflux following peroral endoscopic myotomy for achalasia:Bumps in the road to success

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World Journal of Gastroenterology 2024年第29期30卷 3461-3464页

作者： David Itskoviz Stephen David howard Malnick Kaplan Medical Center Institute of Gastroenterology and HepatologyHebrew University Medical School of JerusalemRehovot 76100Israel Kaplan Medical Center Department of Internal Medicine CHebrew University Medical School of JerusalemRehovot 76100Israel

Achalasia can significantly impair the quality of *** clinical presentation typically includes dysphagia to both solids and liquids,chest pain,and *** can be delayed in patients with atypical presentations,and they might receive a wrong diagnosis,such as gastroesophageal reflux disease(GERD),owing to overlapping symptoms of both *** the cause of achalasia is poorly understood,its impact on the motility of the esophagus and gastroesophageal junction is well *** treatment modalities have been utilized,with the most common being surgical Heller myotomy with concomitant fundoplication and pneumatic balloon ***,peroral endoscopic myotomy(POEM)has gained popularity as an effective treatment for achalasia,despite a relatively high incidence of GERD occurring after treatment compared to other *** magnitude of post-POEM GERD depends on its definition and is influenced by patient and procedure-related *** longterm sequelae of post-POEM GERD are yet to be determined,but it appears to have a benign course and is usually manageable with clinically available *** risk factors for post-POEM GERD and modifying the POEM procedure in selected patients may improve the overall success of this technique.

关键词： Achalasia Per-oral endoscopic myotomy Gastroesophageal reflux Pneumatic dilatation Heller myotomy Proton pump inhibitor Acidic fermentation

Impact of Proteinuria on Liver Enzyme Levels

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Journal of Clinical and Translational Hepatology 2024年第9期12卷 759-760页

作者： David Yardeni Asif Hitawala Lilian howard Theo Heller Meryl Waldman Department of Gastroenterology and Liver Diseases Soroka University Medical CenterBeer-ShevaIsrael Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaMDUSA Kidney Diseases Branch National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaMDUSA

Dear Editors,We read with great interest the recently published article“Subnormal Serum Liver Enzyme Levels:A Review of Pathophysiology and Clinical Significance”by Youssef and colleagues.1 While much attention is given to elevations of liver enzymes,the authors highlight clinically important,often unrecognized reasons leading to low liver enzyme *** example,chronic kidney disease was cited as a cause of low serum aspartate aminotransferase(AST)proportional to the progression of the disease,but the cause(s)are not well *** is known about the possible influence of nephrotic syndrome(NS)on liver enzymes.

关键词： Impact Liver Levels

Quantification and visualization of spatial distribution of dendrites in solid polymer electrolytes

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eScience 2024年第1期4卷 114-122页

作者： Tiancheng Yi Enyue Zhao Yuping He Tianjiao Liang howard Wang Spallation Neutron Source Science Center Dongguan 523803China Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China Neutron Science Platform Songshan Lake Materials LaboratoryDongguan 523808China Institute for Materials Research and Department of Mechanical Engineering Binghamton UniversityBinghamtonNY 13902USA Department of Materials Science and Engineering University of MarylandCollege ParkMD 20742USA

Integrating lithium metal anodes with polymer electrolytes is a promising technology for the next generation high-energy-density rechargeable *** the progress is often hindered by the dendrite growth upon cycling,quantifying three-dimensional(3D)microstructures of dendrites in polymer electrolytes is essential to better understanding of dendrite formation for the development of mitigation *** for 3D quantification and visualization of dendrites,especially those with low Li contents,are rather *** study reports quantitative measurements of the spatial distribution of Li dendrites grown in solid polymer electrolytes using 3D tomographic neutron depth profiling(NDP)with improved spatial resolution,compositional range,and data *** reveal heterogeneous distribution of Li over length scales from tens nanometers to *** most dendrites grow from the plating toward the stripping electrode with dwindling Li quantities,dendrites apparently grown from the Li-stripping electrode are also *** discovery is only possibly due to the unique combination of the high specificity and high sensitivity of the neutron activation analysis of Li isotope.

关键词： Li metal battery Solid polymer electrolytes 3D tomographic neutron depth profiling Lithium dendrite

Peri-articular elbow fracture fixations with magnesium implants and a review of current literature: A case series

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World Journal of Orthopedics 2024年第3期15卷 215-229页

作者： Christopher Fang Antony Xavier Rex Premchand Derek howard Park Dong Hao Toon Department of Orthopaedic Surgery Khoo Teck Puat HospitalNational Healthcare GroupSingapore 768828Singapore

BACKGROUND In recent years,the use of Magnesium alloy implants have gained renewed popularity,especially after the first commercially available ConformitéEuropéenne approved Magnesium implant became available(MAGNEZIX®CS,Syntellix)in *** To document our clinical and radiographical outcomes using magnesium implants in treating peri-articular elbow *** Our paper was based on a retrospective case series ***-operatively,a standardized surgical technique was utilized for insertion of the magnesium ***–operatively,clinic visits were standardized and physical exam findings,functional scores,and radiographs were obtained at each *** complications were *** Five patients with 6 fractures were recruited(2 coronoid,3 radial head and 1 capitellum).The mean patient age and length of follow up was 54.6 years and 11 months *** fractures healed,and none exhibited loss of reduction or complications requiring revision *** patient developed synovitis of the elbow joint or suffered electrolytic reactions when titanium implants were used *** Although there is still a paucity of literature available on the subject and further studies are required,magnesium implants appear to be a feasible tool for fixation of peri-articular elbow fractures with promising results in our *** In recent years,the use of Magnesium alloy implants in orthopaedic surgeries have gained renewed *** from being bioabsorbable,negating the need for implant removal,magnesium also has good osteoconductive properties[1-4].Biomechanically,it exhibits greater biomechanical strength than any pre-existing polymers,and reduces the stress-shielding effect associated with titanium and steel implants as it has a Young’s modulus closer to bone[4].Currently,the main utility of magnesium implants in the orthopaedic community is within the foot and ankle community where satisfactory results have been reported

关键词： Magnesium screw Fracture Peri-articular Elbow

Nano-revolution in hepatocellular carcinoma:A multidisciplinary odyssey-Are we there yet?

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World Journal of Hepatology 2024年第5期16卷 684-687页

作者： howard D Lee Li-Yun Yuan Department of Medicine Division of Gastrointestinal and Liver DiseasesKeck School of Medicine of University of Southern CaliforniaLos AngelesCA 90033United States

In this editorial we comment on the review by Zhou et al reviewing the landscape of nanomedicine in the treatment of hepatocellular carcinoma(HCC).We focus on the immense potential of nanotechnology,particularly ligand-receptor mediated nanotherapy,in revolutionizing the treatment landscape of *** advan-cements in multidisciplinary treatment,HCC remains a significant global health ***-mediated nanotherapy offers the opportunity for precise drug delivery to tumor sites,targeting specific receptors overexpressed in HCC cells,thereby enhancing efficacy and minimizing side *** drug resistance and aggressive tumor biology is facilitated by nanomedicine,bypassing traditional hurdles encountered in *** include targeting glypican-3,asialoglycoprotein,transferrin receptor or folic acid receptors,capitalizing on their over-expression in tumor *** ability for multi-receptor targeting through dual-ligand nanoparticle modification holds the prospect of further enhancement in specificity and efficacy of directed ***,challenges including immune responses,reproducibility in nanoparticle synthesis,and production scalability *** directions involve refining targeting strategies,improving drug release mechanisms,and streamlining production processes to enable personalized and multifunctional ***,the integration of nanotherapy in HCC treatment holds immense promise,but continued partnership and effort are needed in offering hope for more effective,precise,and accessible clinical care in the management of HCC.

关键词： Hepatocellular carcinoma Nanomedicine Ligand-receptor mediated nanotherapy Precision medicine Personalized medicine Targeting

From non-alcoholic fatty liver disease to metabolic-associated steatotic liver disease:Rationale and implications for the new terminology

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World Journal of Hepatology 2024年第6期16卷 863-866页

作者： Stephen David howard Malnick Doron Zamir Department of Internal Medicine C Kaplan Medical CenterRehovot 76100Israel Department of Internal Medicine D Barzilai Medical CenterAshkelon 7830604Israel

Non-alcoholic fatty liver disease(NAFLD)was the term first used to describe hepatic steatosis in patients with the metabolic syndrome who did not consume excess amounts of *** liver disease(ALD)has many similarities to NAFLD in both pathogenesis and *** entity is now the most prevalent chronic liver disease worldwide as a consequence of the epidemic of *** to incorporate the importance of the metabolic syndrome in the development of steatosis resulted in the renaming of NAFLD as metabolic-associated fatty liver *** new term,however,has the disadvantage of the use of terms that may be perceived as *** terms fatty and non-alcoholic have negative connotations in many *** addition,non-alcoholic is not usually a term applicable to pediatric cases of hepatic ***,an international collaborative effort,with participants from 56 countries,after a global consultation process,recommended to change the nomenclature to steatotic liver disease-including metabolic dysfunction-associated steatotic liver disease,metabolic-associated steatohepatitis and metabolic dysfunction-associated *** new terminology is consistent with most of the previously published epidemiological studies and will have a major impact on research into diagnosis,prognosis and treatment.

关键词： Non-alcoholic fatty liver disease Steatosis metabolic-associated steatotic liver disease Nomenclature

The NORE1A/RASSF5 Tumor Suppressor Forms a Complex with GSK-3β to Regulate β-Catenin

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Journal of Biosciences and Medicines 2024年第8期12卷 60-75页

作者： M. Lee Schmidt howard Donninger Geoffrey J. Clark Department Pharmacology and Toxicology University of Louisville Louisville USA US Worldmeds LouisvilleUSA Department of Medicine University of Louisville Louisville USA Experimental Therapeutics Program James Graham Brown Cancer Center University of Louisville Louisville USA

NORE1A (RASSF5) is a tumor suppressor of the RASSF family that is often down-regulated in human tumors. NORE1A has multiple roles in controlling cellular homeostasis, one of them being regulating levels of β-catenin by binding and modulating the ubiquitin ligase substrate recognition factor β-TrCP. β-catenin is a major executor of the Wnt pathway. The ubiquitin SCF-β-TrCP ligase complex acts on a phospho-degron site in β-catenin that can be phosphorylated by GSK-3β. We now show that in addition to binding β-TrCP, NORE1A also promotes the phosphorylation of the β-catenin phospho-degron by complexing with the kinase GSK-3β. Indeed, NORE1A enhances the formation of a GSK-3β/β-TrCP complex. A structural mutant of NORE1A that retains β-TrCP binding but will no longer interact with GSK-3β inhibits the β-catenin degrading action of NORE1A. The GSK-3β interaction with NORE1A plays an important role in the biology of NORE1A as a GSK-3β inhibitor blocks NORE1A induced senescence. Thus, we identify a new role for the tumor suppressor NORE1A: The regulation of GSK-3β. GSK-3β has many other substrates including multiple transcription factors and co-activators such as p53 and the Hippo component TAZ. The work implies that NORE1A may be able to influence all of them via this new kinase scaffolding interaction.

关键词： RAS NORE1A RASSF5 GSK-3β Beta Catenin HIPPO