Article
Neurosciences
Dan-Dan Wang, Mitali Katoch, Samir Jabari, Ingmar Blumcke, David B. B. Blumenthal, De-Hong Lu, Roland Coras, Yu-Jiao Wang, Jie Shi, Wen-Jing Zhou, Katja Kobow, Yue-Shan Piao
Summary: Focal Cortical Dysplasia (FCD) is a common cause of drug-resistant focal epilepsy in children and young adults. This study investigated the DNA methylation signature of a new subtype of FCD 3D and found distinct differences in DNA methylation patterns compared to other FCD subtypes or controls. The DNA methylation signature in FCD 3D was associated with specific histopathology subtypes and biological pathways related to neurodegeneration and cytoskeleton regulation. These findings suggest the importance of DNA methylation in cortical malformations and its relevance to epilepsy.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Letter
Clinical Neurology
Juri-Alexander Witt, Albert J. Becker, Christoph Helmstaedter
Summary: In response to the review by Zawar and Kapur, we highlight the bidirectionality between epilepsy and dementia, summarize the multifactorial etiology of cognitive deficits in epilepsy, emphasize the prevalent neuropathological findings in MTLE, and state the potential adverse effects of anti-seizure medication on cognition. We conclude that the neuropsychology and neuropathology of MTLE is more complex than suggested in the review, and further studies are needed to explore the role of hyperphosphorylated tau in epilepsy patients with and without AD.
ALZHEIMERS & DEMENTIA
(2023)
Review
Oncology
Conor E. Steuer, Glenn J. Hanna, Kartik Viswanathan, James E. Bates, Azeem S. Kaka, Nicole C. Schmitt, Alan L. Ho, Nabil F. Saba
Summary: Salivary gland cancers are rare and histologically diverse tumors that can range from indolent to aggressive, causing significant morbidity and mortality. Surgical resection is the main treatment, but radiation and systemic therapy are also critical. Due to their rarity and heterogeneity, a multidisciplinary approach is best for managing these cancers. This review highlights current standards of care and exciting new research aiming to improve patient outcomes for salivary gland cancers.
CA-A CANCER JOURNAL FOR CLINICIANS
(2023)
Review
Medicine, General & Internal
Jason Weatherald, Athenais Boucly, Anthony Peters, David Montani, Krishna Prasad, Mitchell A. Psotka, Faiez Zannad, Mardi Gomberg-Maitland, Vallerie McLaughlin, Gerald Simonneau, Marc Humbert
Summary: Despite advancements in pulmonary arterial hypertension treatment, prognosis remains poor. Novel therapies targeting vascular remodeling and innovative clinical trial designs are needed to improve outcomes.
Review
Oncology
Pasquale Pisapia, Vincenzo L'Imperio, Francesca Galuppini, Elham Sajjadi, Alessandro Russo, Bruna Cerbelli, Filippo Fraggetta, Giulia D'Amati, Giancarlo Troncone, Matteo Fassan, Nicola Fusco, Fabio Pagni, Umberto Malapelle
Summary: Anatomic pathology has undergone significant changes in recent years, with molecular profiling becoming equally important in cancer diagnosis. Modern pathologists must acquire additional knowledge in predictive molecular pathology to bridge the gap between clinicians and molecular biologists, and they play a growing role in the management of cancer patients.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Review
Pharmacology & Pharmacy
Avijeet S. Chopra, Ronan Lordan, Olaf K. Horbanczuk, Atanas G. Atanasov, Ishveen Chopra, Jaroslaw O. Horbanczuk, Artur Jozwik, Linfang Huang, Vasil Pirgozliev, Maciej Banach, Maurizio Battino, Nicolas Arkells
Summary: The nutraceutical market is a multi-billion-dollar industry with significant impact, expected to grow rapidly in the future. Market opportunities and regulations drive industry development, though challenges exist in regulatory and definitional coherence internationally.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Clinical Neurology
Ingmar Blumcke, Fernando Cendes, Hajime Miyata, Maria Thom, Eleonora Aronica, Imad Najm
Summary: FCD is the most common cause of drug-resistant focal epilepsy in children and young adults, and the diagnosis relies on histopathological assessment of surgical brain tissue. Challenges exist in diagnosing FCD and its subtypes, necessitating continuous research and consensus for a reliable classification scheme. Combining clinical, imaging, histopathology, and molecular studies will help define the disease spectrum and develop specific treatment options for FCD.
Article
Pharmacology & Pharmacy
Palak P. Oza, Khosrow Kashfi
Summary: Cancer is a global burden that affects premature mortality, productivity loss, healthcare expenditures, and mental health. Recent research has revealed a new role for cholesterol-lowering PCSK9 inhibitors in cancer treatment. PCSK9 is an enzyme that degrades LDL receptors, responsible for cholesterol clearance. By inhibiting PCSK9, LDL receptors are upregulated, leading to cholesterol reduction. The cholesterol-lowering effects of PCSK9 inhibitors have potential in combating cancer growth and enhancing existing anticancer therapies.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Gastroenterology & Hepatology
Sanchit Gupta, Benjamin H. Mullish, Jessica R. Allegretti
Summary: Fecal microbiota transplantation (FMT) is recommended for recurrent Clostridioides difficile infection (CDI) treatment, although it is considered investigational and poses potential risks, including multidrug-resistant organisms. Regulatory agencies have raised concerns, leading to variability in how FMT is characterized and additional screening mandates from the FDA. The evolving risk landscape of FMT warrants further examination.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Alessandro Di Minno, Monica Gelzo, Mariano Stornaiuolo, Margherita Ruoppolo, Giuseppe Castaldo
Summary: Untargeted Metabolomics and targeted Metabolomics have made significant progress in the field of life sciences, particularly in the discovery of biomarkers. Expertise in laboratory medicine and bioinformatics helps address challenges and biases in metabolite profiling. Clinical validation and profitability testing are essential steps in identifying potential biomarkers.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2021)
Review
Chemistry, Multidisciplinary
Karol Kowalski, Raymond Bair, Nicholas P. Bauman, Jeffery S. Boschen, Eric J. Bylaska, Jeff Daily, Wibe A. de Jong, Thom Dunning, Niranjan Govind, Robert J. Harrison, Murat Keceli, Kristopher Keipert, Sriram Krishnamoorthy, Suraj Kumar, Erdal Mutlu, Bruce Palmer, Ajay Panyala, Bo Peng, Ryan M. Richard, T. P. Straatsma, Peter Sushko, Edward F. Valeev, Marat Valiev, Hubertus J. J. van Dam, Jonathan M. Waldrop, David B. Williams-Young, Chao Yang, Marcin Zalewski, Theresa L. Windus
Summary: Chemists have been utilizing computers since the beginning to understand and solve complex chemical problems. With advancements in hardware and software, the field of theoretical and computational chemistry has evolved. Transitioning software from terascale to petascale and now to exascale computers presents challenges and opportunities for tackling large scientific challenges. One example highlighted is the NWCHEM and its redesign, NWCHEMEX, which is a codesign project aiming to take advantage of massively parallel computers and emerging software standards.
Review
Biochemistry & Molecular Biology
Danielle J. Beetler, Damian N. Di Florio, Ethan W. Law, Chris M. Groen, Anthony J. Windebank, Quinn P. Peterson, DeLisa Fairweather
Summary: Regenerative medicine is a new component of modern medicine that includes cellular and acellular therapies, and regulatory agencies like FDA have adapted existing frameworks and generated new ones to regulate this field. This review discusses the current state of FDA regulatory affairs in the context of stem cells and extracellular vesicles, highlighting gaps in the current system and the potential future of regulatory science in regenerative medicine. Case studies in stem cell and acellular based treatments are utilized to demonstrate the evolution of regulatory science and the ongoing efforts and challenges in these therapies.
MOLECULAR ASPECTS OF MEDICINE
(2023)
Article
Clinical Neurology
Qi Zhang, Ana Suller-Marti, Jane Jian Ding, Gansen Deng, Wenqing He, Jorge G. Burneo, Robert R. Hammond, Lee-Cyn Ang
Summary: Patients with epilepsy are at increased risk for premature death, and SUDEP is one of the main causes. This study reviewed epilepsy-related deaths from 2000 to 2018 and identified characteristics associated with SUDEP. The revised coroner act had an impact on the investigation of epilepsy-related deaths. This is the first detailed clinical-pathological study based on a Canadian cohort, reinforcing previous findings and emphasizing the importance of clinicopathological correlation in accurate classification of epilepsy-related deaths.
Editorial Material
Urology & Nephrology
Abdullah Jalal, Tingting Li
Summary: Trial data on therapeutic interventions in IgA nephropathy and lupus nephritis, along with the discovery of autoantibodies targeting nephrin in minimal change disease, can provide guidance for the management of immune-mediated glomerular diseases.
NATURE REVIEWS NEPHROLOGY
(2023)
Article
Ecology
Maximilian Mcquillan, Ren Ryba
Summary: In landscape design and ecological restoration, humans shape the landscape and express values that constantly evolve. These values have been contested throughout history and continue to be negotiated today, forming the evolving circle of landscape design. Understanding and reflecting on the values expressed in landscape design and restoration can empower practitioners to choose which values are expressed in landscapes, enabling our disciplines to address present and future challenges.
RESTORATION ECOLOGY
(2023)
Article
Clinical Neurology
Yueqiu Sun, Daniel Friedman, Patricia Dugan, Manisha Holmes, Xiaojing Wu, Anli Liu
Summary: This study aimed to explore the application of machine learning algorithms in responsive neurostimulation therapy to assess the clinical response to changes in neurostimulation parameters. By analyzing the data and training models, it was found that high gamma power was one of the most informative features, and individual circadian patterns of seizure activity could guide model building.
JOURNAL OF CLINICAL NEUROPHYSIOLOGY
(2023)
Article
Clinical Neurology
Jacqueline French, Victor Biton, Hina Dave, Kamil Detyniecki, Michael A. Gelfand, Hui Gong, Kore Liow, Terence J. O'Brien, Ahmed Sadek, Bree DiVentura, Brittany Reich, Jouko Isojarvi
Summary: This study demonstrated that Staccato alprazolam administered via a breath-actuated device can rapidly terminate epileptic seizures in hospitalized patients. The next step is to conduct a Phase 3 confirmatory study to further evaluate the efficacy and safety of Staccato alprazolam for seizure termination in an outpatient setting.
Article
Clinical Neurology
Dominique F. Leitner, Ziyan Lin, Zacharia Sawaged, Evgeny Kanshin, Daniel Friedman, Sasha Devore, Beatrix Ueberheide, Julia W. Chang, Gary W. Mathern, Jasper J. Anink, Eleonora Aronica, Thomas Wisniewski, Orrin Devinsky
Summary: This study used whole exome sequencing (WES), RNAseq, and proteomics to investigate the molecular mechanisms in Rasmussen encephalitis (RE) compared to non-RE epilepsy (PWE) and a control group. The results showed activated immune signaling pathways and involvement of dendritic and natural killer cells in RE. Additionally, HLA variants may contribute to susceptibility to RE.
Article
Clinical Neurology
Russell Nightscales, Sarah Barnard, Juliana Laze, Zhibin Chen, Gerard Tao, Clarissa Auvrez, Shobi Sivathamboo, Mark J. Cook, Patrick Kwan, Daniel Friedman, Samuel F. Berkovic, Wendyl D'Souza, Piero Perucca, Orrin Devinsky, Terence J. O'Brien
Summary: This study aimed to investigate the association between lamotrigine and sudden unexpected death in epilepsy (SUDEP). The retrospective, nested case-control study included 101 SUDEP cases and 199 living epilepsy controls from Australia and the USA. The results showed no increased risk of SUDEP associated with the use of lamotrigine or other sodium channel modulating anti-seizure medications.
Review
Clinical Neurology
Wesley T. Kerr, Stephane Auvin, Serge Van der Geyten, Christopher Kenney, Gerald Novak, Nathan B. Fountain, Caitlin Grzeskowiak, Jacqueline A. French
Summary: Well-designed placebo-controlled clinical trials are crucial for the development of new epilepsy treatments, but the design has remained unchanged for decades. Concerns have been raised by patients, clinicians, regulators, and innovators about the challenges of recruiting for trials, partly due to the static design of maintaining participants on add-on placebo for long periods of time when there are more therapy options available. Time-to-event trials, although having potential limitations, have been suggested as a promising mechanism to make trials more patient-friendly and reduce placebo exposure.
Article
Clinical Neurology
Wesley T. Kerr, Hai Chen, Mariana Figuera Losada, Christopher Cheng, Tiffany Liu, Jaqueline French
Summary: Selection criteria for clinical trials in medication-resistant epilepsy aim to ensure safety and limit variability, but it is increasingly difficult to recruit subjects. This study investigated the impact of these criteria on recruitment at an academic epilepsy center. The majority of patients were excluded due to insufficient seizure frequency. A small proportion of patients were eligible based on common criteria, but may not be representative of the overall population.
Article
Clinical Neurology
Dominique F. Leitner, Yik Siu, Aryeh Korman, Ziyan Lin, Evgeny Kanshin, Daniel Friedman, Sasha Devore, Beatrix Ueberheide, Aristotelis Tsirigos, Drew R. Jones, Thomas Wisniewski, Orrin Devinsky
Summary: High-fat and low-carbohydrate diets, such as the modified Atkins diet (MAD), can reduce seizure frequency in treatment-resistant epilepsy patients. These diets mimic fasting and induce high levels of ketone bodies, potentially shifting brain energy production and impacting neuronal and astrocyte metabolism.
Article
Clinical Neurology
Adam C. Gravitis, Uilki Tufa, Katherine Zukotynski, David L. Streiner, Daniel Friedman, Juliana Laze, Yotin Chinvarun, Orrin Devinsky, Richard Wennberg, Peter L. Carlen, Berj L. Bardakjian
Summary: Previous case-control studies were unable to identify ECG features associated with SUDEP risk, leading to the development of a novel metric called alpha. This study used Single Spectrum Analysis, Independent Component Analysis, and cross-frequency phase-phase coupling to assess SUDEP risk and found that alpha was higher in SUDEP patients and predictive of SUDEP risk.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
P. Emanuela Voinescu, McKenna Kelly, Jacqueline A. French, Cynthia Harden, Anne Davis, Connie Lau, Alexa Ehlert, Stephanie Allien, Emma Osterhaus, Sarah Barnard, Rishabh Jain, Page B. Pennell
Summary: This study examined the occurrence and distribution of catamenial epilepsy patterns in women with epilepsy not receiving hormonal therapies. The results showed that out of 89 women enrolled, 23 were eligible for analysis, with 12 meeting criteria for catamenial epilepsy. App-based tracking proved to be a useful tool in determining catamenial patterns.
Article
Clinical Neurology
Wesley T. T. Kerr, Advith S. S. Reddy, Sung Hyun Seo, Neo Kok, William C. C. Stacey, John M. M. Stern, Page B. B. Pennell, Jacqueline A. A. French
Summary: This study aimed to assess the changes in recruitment and retention challenges in clinical trials for focal onset epilepsy over time. A systematic analysis of randomized clinical trials was conducted to evaluate changes in participant numbers, trial sites, and countries since 1990. The study also analyzed the proportion of participants who completed each trial phase and the reasons for early trial exit. The findings highlight increasing challenges with participant recruitment and retention, as well as an increasing placebo response, emphasizing the need for changes in clinical trial design.
Article
Clinical Neurology
Jacob Pellinen, Heath Pardoe, Stefan Sillau, Sarah Barnard, Jacqueline French, Robert Knowlton, Daniel D. Lowenstein, Gregory Cascino, Simon Glynn, Graeme Jackson, Jerzy Szaflarski, Chris J. Morrison, Kimford Meador, Ruben Kuzniecky, Human Epilepsy Project Investigators
Summary: This study found that people with newly treated focal epilepsy and learning difficulties have lower brain tissue volume to intracranial volume, suggesting that developmental factors are an important marker of neuroanatomical changes in focal epilepsy. There were also independent associations between brain volume, age, and sex in the study population.
Article
Clinical Neurology
Jonah Fox, Sarah Barnard, Shruti H. Agashe, Manisha G. Holmes, Barry Gidal, Pavel Klein, Bassel W. Abou-Khalil, Jacqueline French, Human Epilepsy Project Investigators
Summary: More than one third of patients with focal epilepsy remain on monotherapy with their initial prescribed ASM. Approximately three out of five patients transition to monotherapy with another ASM, while approximately two out of five end up on polytherapy. Patients stay on lamotrigine for a longer duration compared to levetiracetam when it is prescribed as the initial monotherapy.
Article
Pharmacology & Pharmacy
Jessica M. Barry, Jacqueline A. French, Page B. Pennell, Ashwin Karanam, Cynthia L. Harden, Angela K. Birnbaum
Summary: This study aims to investigate the complexity of maintaining seizure control with lamotrigine during pregnancy and evaluate the potential risks of different dosing scenarios. The results suggest that some dosing regimens may increase seizure risk or toxicity. Early clearance changes during pregnancy may require therapeutic drug monitoring to determine whether the patient belongs to the low clearance change group or the high clearance change group.
Article
Clinical Neurology
Levente Hadady, Michael R. Sperling, Juan Luis Alcala-Zermeno, Jacqueline A. French, Patricia Dugan, Lara Jehi, Daniel Fabo, Peter Klivenyi, Guido Rubboli, Sandor Beniczky
Summary: This study conducted external validation of previously published epilepsy surgery prediction tools using a large independent multicenter dataset and found that these tools can effectively stratify patients for surgery and freedom from disabling seizures.
Article
Psychology, Clinical
Margaret Miller, Ryan Honomichl, Brittany Lapin, Thomas Hogan, Nicholas Thompson, William B. Barr, Daniel Friedman, Erica Sieg, Stephan Schuele, Selin Yagci Kurtish, Cigdem ozkara, Katia Lin, Samuel Wiebe, Lara Jehi, Robyn M. Busch
Summary: This study aimed to evaluate subjective memory complaints in patients with epilepsy using the Memory Assessment Clinics Self-Rating Scale (MAC-S) and to create a shorter version - the Memory Assessment Clinics Scale for Epilepsy (MAC-E). Through various analyses, a five-factor structure was identified and the MAC-E was reduced from 49 to 30 items.
CLINICAL NEUROPSYCHOLOGIST
(2022)
