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REVIEW
Maria Bonomi, Daniele Spada, Gian Luca Baiocchi, Andrea Celotti, Matteo Brighenti, Giulia Grizzi
Gastroesophageal adenocarcinoma (GEA) is one of the principal causes of death related to cancer globally. Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor which is found to be overexpressed or amplified in approximately 20% of GEA cases. In GEA, the identification of HER2-positive status is crucial to activate a specific anti-HER2 targeted therapy. The landmark ToGA trial demonstrated the superiority of adding trastuzumab to platinum-based chemotherapy, becoming the first-line standard of treatment...
March 30, 2024: International Journal of Molecular Sciences
#2
REVIEW
Magdalena K Scheck, Ralf D Hofheinz, Sylvie Lorenzen
Despite a decreasing incidence in Western countries, gastric cancer is among the most common cancer subtypes globally and is associated with one of the highest tumor-related mortality rates. Biomarkers play an increasing role in the treatment against gastric cancer. HER2 was one of the first biomarkers that found its way into clinical practice. Since the ToGA trial, trastuzumab has been part of first-line palliative chemotherapy in metastatic or unresectable gastric cancer. HER2-targeting agents, such as the tyrosine kinase inhibitor lapatinib, the antibody drug conjugate (ADC) trastuzumab-emtansine or dual HER2 inhibition (pertuzumab and trastuzumab), have been investigated in the second-line setting but led to negative study results...
March 29, 2024: Cancers
#3
JOURNAL ARTICLE
Junhao Wen, Bingxin Zhao, Zhijian Yang, Guray Erus, Ioanna Skampardoni, Elizabeth Mamourian, Yuhan Cui, Gyujoon Hwang, Jingxuan Bao, Aleix Boquet-Pujadas, Zhen Zhou, Yogasudha Veturi, Marylyn D Ritchie, Haochang Shou, Paul M Thompson, Li Shen, Arthur W Toga, Christos Davatzikos
The complex biological mechanisms underlying human brain aging remain incompletely understood. This study investigated the genetic architecture of three brain age gaps (BAG) derived from gray matter volume (GM-BAG), white matter microstructure (WM-BAG), and functional connectivity (FC-BAG). We identified sixteen genomic loci that reached genome-wide significance (P-value < 5×10-8 ). A gene-drug-disease network highlighted genes linked to GM-BAG for treating neurodegenerative and neuropsychiatric disorders and WM-BAG genes for cancer therapy...
March 23, 2024: Nature Communications
#4
REVIEW
Jaeyop Lee, Geoffrey Ku
The Trastuzumab for Gastric Cancer (ToGA) trial marked a pivotal moment in the adoption of trastuzumab for treating advanced human epidermal growth factor receptor 2 (HER2)-positive esophagogastric (EG) cancer. The KEYNOTE-811 trial brought to light the synergistic effect of immune modulation and HER2 targeting. Additionally, the emergence of trastuzumab deruxtecan (T-DXd) highlighted the potential of new pharmaceutical technologies to extend response, particularly for patients who have advanced beyond initial HER2-targeted therapies...
March 22, 2024: Hematology/oncology Clinics of North America
#5
JOURNAL ARTICLE
Hirokazu Takeuchi, Norimichi Higurashi, Yurika Toga
PURPOSE: The management of status epilepticus (SE) has mainly focused on the termination of ongoing SE episodes. However, long-term therapeutic strategies for the prevention of SE are lacking. This study aimed to investigate the effectiveness of prophylactic antiseizure medications (ASMs) for SEs in nonsyndromic childhood epilepsy. METHODS: This retrospective study was conducted at Jikei University Hospital. Patients <18 years of age, diagnosed with epilepsy, and experiencing three or more SE episodes within 1 year between April 1, 2017, and October 1, 2021, were included...
March 21, 2024: Brain & Development
#6
JOURNAL ARTICLE
Rachel Han, Ainhoa Madariaga, Eduardo Gonzalez-Ochoa, Adam C Smith, Lisa Wang, Stephanie Lheureux, Marjan Rouzbahman
Mucinous ovarian carcinoma is an uncommon malignancy characterized by resistance to chemotherapy and poor survival in the metastatic setting. HER2 amplification is a frequent late event in carcinogenesis, yet the incidence of HER2-low in mucinous ovarian carcinoma is unknown. Further, the optimal method for determining overexpression in these tumors is not established. We sought to assess the ASCO/CAP and ToGA trial scoring methods for HER2 IHC with correlation to FISH, p53, and mismatch repair protein status and to determine the incidence of HER2-low in mucinous ovarian carcinoma...
March 4, 2024: International Journal of Gynecological Pathology
#7
JOURNAL ARTICLE
Hidetaka Wakabayashi, Shingo Kakehi, Satoko Mizuno, Tomoko Kinoshita, Sayaka Toga, Masahiro Ohtsu, Shinta Nishioka, Ryo Momosaki
OBJECTIVE: The aim is to examine the prevalence and prognosis of cachexia according to the Asian Working Group for Cachexia (AWGC) criteria in patients with sarcopenic dysphagia. METHODS: A retrospective cohort study was conducted with 271 patients diagnosed with sarcopenic dysphagia out of 467 patients enrolled in the Japanese sarcopenic dysphagia database. Cachexia was diagnosed by the AWGC criteria. The AWGC criteria includes chronic diseases, either or both weight loss (2% or more over 3-6 mo) or low BMI (<21 kg/m2 ), and at least one of the following: anorexia, decreased grip strength (<28 kg in men and <18 kg in women), or elevated C-reactive protein levels (>0...
February 6, 2024: Nutrition
#8
JOURNAL ARTICLE
George Alexias, Maria Papandreopoulou, Constantinos Togas
Work engagement represents a positive work-related state of mind characterized by three dimensions: Vigor (high levels of energy and mental resilience during work), Dedication (strong involvement in one's work), and Absorption (complete-joyous immersion in one's tasks). This study aimed to investigate work engagement and burnout in health professionals in a private healthcare unit in Greece. A cross-sectional study was conducted with a sample of 151 professionals, including doctors, nurses, administrative staff, and other health professionals involved in this setting...
January 25, 2024: International Journal of Environmental Research and Public Health
#9
JOURNAL ARTICLE
Yury V Bukhman, Phillip A Morin, Susanne Meyer, Li-Fang Chu, Jeff K Jacobsen, Jessica Antosiewicz-Bourget, Daniel Mamott, Maylie Gonzales, Cara Argus, Jennifer Bolin, Mark E Berres, Olivier Fedrigo, John Steill, Scott A Swanson, Peng Jiang, Arang Rhie, Giulio Formenti, Adam M Phillippy, Robert S Harris, Jonathan M D Wood, Kerstin Howe, Bogdan M Kirilenko, Chetan Munegowda, Michael Hiller, Aashish Jain, Daisuke Kihara, J Spencer Johnston, Alexander Ionkov, Kalpana Raja, Huishi Toh, Aimee Lang, Magnus Wolf, Erich D Jarvis, James A Thomson, Mark J P Chaisson, Ron Stewart
The blue whale, Balaenoptera musculus, is the largest animal known to have ever existed, making it an important case study in longevity and resistance to cancer. To further this and other blue whale-related research, we report a reference-quality, long-read-based genome assembly of this fascinating species. We assembled the genome from PacBio long reads and utilized Illumina/10X, optical maps, and Hi-C data for scaffolding, polishing, and manual curation. We also provided long read RNA-seq data to facilitate the annotation of the assembly by NCBI and Ensembl...
February 20, 2024: Molecular Biology and Evolution
#10
JOURNAL ARTICLE
Katheryn A Q Cousins, David J Irwin, Thomas F Tropea, Emma Rhodes, Jeffrey Phillips, Alice S Chen-Plotkin, Michael C Brumm, Christopher S Coffey, Ju Hee Kang, Tanya Simuni, Tatiana M Foroud, Arthur W Toga, Caroline M Tanner, Karl D Kieburtz, Brit Mollenhauer, Douglas Galasko, Samantha Hutten, Daniel Weintraub, Andrew D Siderowf, Kenneth Marek, Kathleen L Poston, Leslie M Shaw
BACKGROUND AND OBJECTIVES: In Parkinson disease (PD), Alzheimer disease (AD) copathology is common and clinically relevant. However, the longitudinal progression of AD CSF biomarkers-β-amyloid 1-42 (Aβ42 ), phosphorylated tau 181 (p-tau181 ), and total tau (t-tau)-in PD is poorly understood and may be distinct from clinical AD. Moreover, it is unclear whether CSF p-tau181 and serum neurofilament light (NfL) have added prognostic utility in PD, when combined with CSF Aβ42 ...
February 2024: Neurology
#11
JOURNAL ARTICLE
Maria Kryza-Lacombe, Michelle T Kassel, Philip S Insel, Emma Rhodes, David Bickford, Emily Burns, Meryl A Butters, Duygu Tosun, Paul Aisen, Rema Raman, Susan Landau, Andrew J Saykin, Arthur W Toga, Clifford R Jack, Robert Koeppe, Michael W Weiner, Craig Nelson, R Scott Mackin
OBJECTIVES: Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aβ) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD...
January 25, 2024: International Psychogeriatrics
#12
JOURNAL ARTICLE
Masafumi Yamaguchi, Yukihiro Sera, Hanae Toga-Yamaguchi, Hirokazu Kanegane, Yusuke Iguchi, Kingo Fujimura
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency and bone marrow failure. The depletion of SBDS protein by RNA interference has been shown to cause inhibition of cell proliferation in several cell lines. However, the precise mechanism by which the loss of SBDS leads to inhibition of cell growth remains unknown. To evaluate the impaired growth of SBDS-knockdown cells, we analyzed Epstein-Barr virus-transformed lymphoblast cells (LCLs) derived from two patients with SDS (c...
January 19, 2024: International Journal of Hematology
#13
Zhijian Yang, Junhao Wen, Guray Erus, Sindhuja T Govindarajan, Randa Melhem, Elizabeth Mamourian, Yuhan Cui, Dhivya Srinivasan, Ahmed Abdulkadir, Paraskevi Parmpi, Katharina Wittfeld, Hans J Grabe, Robin Bülow, Stefan Frenzel, Duygu Tosun, Murat Bilgel, Yang An, Dahyun Yi, Daniel S Marcus, Pamela LaMontagne, Tammie L S Benzinger, Susan R Heckbert, Thomas R Austin, Shari R Waldstein, Michele K Evans, Alan B Zonderman, Lenore J Launer, Aristeidis Sotiras, Mark A Espeland, Colin L Masters, Paul Maruff, Jurgen Fripp, Arthur Toga, Sid O'Bryant, Mallar M Chakravarty, Sylvia Villeneuve, Sterling C Johnson, John C Morris, Marilyn S Albert, Kristine Yaffe, Henry Völzke, Luigi Ferrucci, Nick R Bryan, Russell T Shinohara, Yong Fan, Mohamad Habes, Paris Alexandros Lalousis, Nikolaos Koutsouleris, David A Wolk, Susan M Resnick, Haochang Shou, Ilya M Nasrallah, Christos Davatzikos
Brain aging is a complex process influenced by various lifestyle, environmental, and genetic factors, as well as by age-related and often co-existing pathologies. MRI and, more recently, AI methods have been instrumental in understanding the neuroanatomical changes that occur during aging in large and diverse populations. However, the multiplicity and mutual overlap of both pathologic processes and affected brain regions make it difficult to precisely characterize the underlying neurodegenerative profile of an individual from an MRI scan...
December 30, 2023: medRxiv
#14
Udit Nindra, Victoria Bray, Deme Karikios, Mohsen Shafiei, Shalini Subramaniam, Pei Ding, Steven Kao, Abhijit Pal
BACKGROUND: Local Australian guidelines for the optimal management of stage III unresectable NSCLC are lacking. The American Society of Clinical Oncology (ASCO) guidelines recommend consolidation durvalumab for all patients with unresectable stage III NSCLC irrespective of their PD-L1 expression or driver mutation status. The European Society of Medical Oncology (ESMO) differs, with consolidation durvalumab only recommended in those patients whose tumours express PD-L1. METHODS: Due to differing global guidelines we conducted an Australia and New Zealand wide survey of medical oncologists specialising in thoracic cancer to determine the variations in patterns of prescribing durvalumab in stage III unresectable NSCLC...
January 17, 2024: Oncology
#15
JOURNAL ARTICLE
Yasutaka Kawasaki, Kazuaki Nishiki, Masafumi Nojiri, Ryo Kato, Shohei Shinomiya, Taku Oikawa, Takeshi Ishizaki, Hirohisa Toga, Shiro Mizuno
BACKGROUND: Sarcopenia, characterized by skeletal muscle atrophy and physical inactivity, is a manifestation of chronic obstructive pulmonary disease (COPD) and is associated with a poor prognosis. The serum creatinine (Cr)/cystatin C (CysC) ratio has been proposed as a marker of sarcopenia, given its correlation with total skeletal muscle mass, and as a prognostic indicator in COPD. This study aimed to evaluate the usefulness of the serum Cr/CysC ratio as a prognostic determinant in these patients...
December 21, 2023: Respiratory Investigation
#16
JOURNAL ARTICLE
Sara Nutley, Binh K Nguyen, Robert Scott Mackin, Philip S Insel, Duygu Tosun, Meryl Butters, Paul Aisen, Rema Raman, Andrew J Saykin, Arthur W Toga, Clifford Jack, Michael W Weiner, Craig Nelson, Michelle Kassel, Maria Kryza-Lacombe, Joseph Eichenbaum, Rachel L Nosheny, Carol A Mathews
Hoarding disorder (HD) is a debilitating neuropsychiatric condition that affects 2%-6% of the population and increases in incidence with age. Major depressive disorder (MDD) co-occurs with HD in approximately 50% of cases and leads to increased functional impairment and disability. However, only one study to date has examined the rate and trajectory of hoarding symptoms in older individuals with a lifetime history of MDD, including those with current active depression (late-life depression; LLD). We therefore sought to characterize this potentially distinct phenotype...
November 23, 2023: American Journal of Geriatric Psychiatry
#17
JOURNAL ARTICLE
Samantha L Cohen, Jeong Woo Choi, Arthur W Toga, Nader Pouratian, Dominique Duncan
Elevated β oscillations (13-35 Hz) are characteristic pathophysiology in Parkinson's Disease (PD). Cortical thinning has also been reported in the disease, however the relationship between these biomarkers of PD has not been established. By comparing electrophysiological measurements with cortical thickness, this study aims to reveal the pathoetiology of disease and symptoms in PD. Preoperative magnetic resonance imaging (MRI) and intraoperative local field potentials (LFPs) were collected from 34 subjects diagnosed with PD...
July 2023: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
#18
JOURNAL ARTICLE
Ioannis Triantafyllakis, Maria Saridi, Aikaterini Toska, Eleni N Albani, Constantinos Togas, Dimitrios K Christodoulou, Konstantinos H Katsanos
OBJECTIVE: Aim: The aim of the study was to investigate the incidence of IBD in gastrointestinal surgery patients and record the disease's characteristics and treatment. PATIENTS AND METHODS: Materials and Methods: A search was carried out in the archives of the gastroenterology clinics of the University General Hospital of Ioannina and the General Hospital of Ioannina "G. Hatzikosta" in Greece. All cases of operated patients from 1980 to 2018 were examined. The duration of the study was 4 months...
2023: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
#19
REVIEW
Ying Li, Lei Yan, Lingyu Hou, Xiaoya Zhang, Hanping Zhao, Chengkun Yan, Xianhuang Li, Yuanhe Li, Xiaoan Chen, Xiaorong Ding
PURPOSE: Chronic low back pain (CLBP) is an aging and public health issue that is a leading cause of disability worldwide and has a significant economic impact on a global scale. Treatments for CLBP are varied, and there is currently no study with high-quality evidence to show which treatment works best. Exercise therapy has the characteristics of minor harm, low cost, and convenient implementation. It has become a mainstream treatment method in clinics for chronic low back pain. However, there is insufficient evidence on which specific exercise regimen is more effective for chronic non-specific low back pain...
2023: Frontiers in Public Health
#20
JOURNAL ARTICLE
Susanne Klein-Scory, Swetlana Ladigan-Badura, Thomas Mika, Berlinda Verdoodt, Andrea Tannapfel, Michael Pohl, Roland Schroers, Alexander Baraniskin
Gastric carcinomas are among the most common cancers in Germany, with approximately 18,000 new cases per year. About 10 years ago, based on results of the Trastuzumab for gastric cancer (ToGA) trial, the addition of the monoclonal antibody trastuzumab to a platinum-fluoropyrimidine chemotherapy backbone became the standard-of-care 1st-line therapy for human epidermal growth factor receptor 2 ( HER2 )-positive gastric cancers. Only patients with primary HER2 gene amplification benefit from this therapy. Thus, accurate HER2 gene amplification detection is predictive and critical for therapy selection...
November 2023: Heliyon
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