tbuckley/cabot-search huggingface dataset:
Flexible Polymer Electrodes for Stable Prosthetic Visual Perception in Mice
Authors: Corinne Orlemann, Christian Boehler, Roxana N. Kooijmans, Bingshuo Li, Maria Asplund, Pieter R. Roelfsema
Journal: Advanced Healthcare Materials (2024)

Brain interfaces that can stimulate neurons, cause minimal damage, and work for a long time will be central for future neuroprosthetics. Here, the long-term performance of highly flexible, thin polyimide shanks with several small (<15 µm) electrodes during electrical microstimulation of the visual cortex, is reported. The electrodes exhibit a remarkable stability when several billions of electrical pulses are applied in vitro. When the devices are implanted in the primary visual cortex (area V1) of mice and the animals are trained to detect electrical microstimulation, it is found that the perceptual thresholds are 2-20 microamperes (µA), which is far below the maximal currents that the electrodes can withstand. The long-term functionality of the devices in vivo is excellent, with stable performance for up to more than a year and little damage to the brain tissue. These results demonstrate the potential of thin floating electrodes for the long-term restoration of lost sensory functions.
Overall Survival From the EORTC LCG-1613 APPLE Trial of Osimertinib Versus Gefitinib Followed by Osimertinib in Advanced <i>EGFR</i>-Mutant Non–Small-Cell Lung Cancer
Authors: Jordi Remon, Benjamin Besse, Santiago Ponce Aix, Ana Callejo, Kamal Al-Rabi, Reyes Bernabe, Laurent Greillier, Margarita Majem, Noemi Reguart, Isabelle Monnet, Sophie Cousin, Pilar Garrido, Gilles Robinet, Rosario Garcia Campelo, Anne Madroszyk, Julien Mazières, Hubert Curcio, Bartosz Wasąg, Yassin Pretzenbacher, Fanny Grillet, Anne-Marie C. Dingemans, Rafal Dziadziuszko
Journal: Journal of Clinical Oncology (2024)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Osimertinib has been established as a standard of care for patients with common sensitizing EGFR-mutant advanced non–small-cell lung cancer (NSCLC) although the sequential approach (first-generation inhibitor gefitinib followed by osimertinib) has not been formally compared. The phase II APPLE trial (ClinicalTrials.gov identifier: NCT02856893 ) enrolled 156 treatment-naïve patients, and two treatment strategies were evaluated: osimertinib up front or the sequential treatment approach with gefitinib up front followed by osimertinib at the time of progression, either molecular progression (detection of plasma T790M resistance mutation) regardless of the radiologic status or just at the time of radiologic progression. Patients' characteristics were well balanced, except for the higher proportion of baseline brain metastases in the sequential approach (29% v 19%). Per protocol, 73% of patients switched to osimertinib in the sequential arm. Up-front treatment with osimertinib was associated with a lower risk of brain progression versus the sequential approach (hazard ratio [HR], 0.54 [90% CI, 0.34 to 0.86]), but a comparable overall survival was observed between both strategies (HR, 1.01 [90% CI, 0.61 to 1.68]), with the 18-month survival probability of 84% and 82.3%, respectively. The APPLE trial suggests that a sequential treatment approach is associated with more frequent progression in the brain but a similar survival in advanced EGFR-mutant NSCLC.
A Treacherous Course
Authors: Natalie Koscal, Suellen Li, Lori A. Messenger, Daniel Muller, Caren G. Solomon
Journal: New England Journal of Medicine (2024)

This Double Take video from the New England Journal of Medicine presents the case of a man with acute onset of nausea, vomiting, abdominal pain, fever, and hemoptysis. Based on a Clinical Problem-Solving article published in the Journal, the video explores the differential diagnosis based on the patient’s presenting symptoms and follows the evolution of the diagnosis as new findings arise from the diagnostic evaluation and the patient’s clinical course. For further reading, the article mentioned above, referenced in the video, is available at NEJM.org: A Treacherous Course (Jilg et al., in the March 4, 2021, issue of the Journal).
Case 4-2024: A 39-Year-Old Man with Fever and Headache after International Travel
Authors: Edward T. Ryan, Marc D. Succi, Molly L. Paras, Erik H. Klontz
Journal: New England Journal of Medicine (2024)

A 39-year-old man was evaluated at the hospital during the summer because of 4 days of fever with shaking chills, headache, and fatigue after returning from travel in East Africa. A diagnosis was made.
An Oral Interleukin-23–Receptor Antagonist Peptide for Plaque Psoriasis
Authors: Robert Bissonnette, Andreas Pinter, Laura K. Ferris, Sascha Gerdes, Phoebe Rich, Ronald Vender, Megan Miller, Yaung-Kaung Shen, Arun Kannan, Shu Li, Cynthia DeKlotz, Kim Papp
Journal: New England Journal of Medicine (2024)

The use of monoclonal antibodies has changed the treatment of several immune-mediated inflammatory diseases, including psoriasis. However, these large proteins must be administered by injection. JNJ-77242113 is a novel, orally administered interleukin-23-receptor antagonist peptide that selectively blocks interleukin-23 signaling and downstream cytokine production.
Case fatality risk among individuals vaccinated with rVSVΔG-ZEBOV-GP: a retrospective cohort analysis of patients with confirmed Ebola virus disease in the Democratic Republic of the Congo
Authors: Rebecca M Coulborn, Mathieu Bastard, Nicolas Peyraud, Etienne Gignoux, Francisco Luquero, Bérengère Guai, Stephane Hans Bateyi Mustafa, Elisabeth Mukamba Musenga, Steve Ahuka-Mundeke
Journal: The Lancet Infectious Diseases (2024)
Expression of concern—Endoscopic ultrasonography-guided gastroenterostomy versus uncovered duodenal metal stenting for unresectable malignant gastric outlet obstruction (DRA-GOO): a multicentre randomised controlled trial
Authors: None The Editors of The Lancet Gastroenterology & Hepatology
Journal: The Lancet. Gastroenterology & hepatology (2024)

In December, 2023, The Lancet Gastroenterology & Hepatology published the results of the DRA-GOO trial,1 which compared endoscopic ultrasonography-guided gastroenterostomy with uncovered duodenal metal stenting for unresectable malignant gastric outlet obstruction.
Why are females less likely to be diagnosed with ADHD in childhood than males?
Authors: Joanna Martin
Journal: The Lancet Psychiatry (2024)

ADHD is less likely to be diagnosed in females than males, especially in childhood. Females also typically receive the diagnosis later than males and are less likely to be prescribed ADHD medication. Understanding why these sex differences in clinical care and treatment for ADHD occur is key to improving timely diagnosis in people affected by ADHD. This Personal View is a conceptual review synthesising literature on this topic. This publication considers potential biological explanations (eg, genetic factors), influence of diagnostic practices (eg, criteria suitability, diagnostic overshadowing, and sex-specific diagnostic thresholds), and sociocultural explanations (eg, sex differences in presentation and compensatory behaviours), for the observed sex differences in ADHD clinical practice. This Personal View also outlines future research directions for improving understanding of sex differences in recognition and diagnosis of ADHD.
Gender authorship in major American and European gastroenterology journals: the gap is still unfilled
Authors: Elisabetta Mastrorocco, Maria Terrin, Giulia Migliorisi, Benedetta Masoni, Valeria Farinola, Diletta De Deo, Silvia Ferretti, Valeria Poletti, Miriana Mercurio, Bianca Bartocci, P. Alessia Galtieri, Gaia Pellegatta, Elisa Ferrara, Silvia Carrara, Amrita Sethi, Uzma D. Siddiqui, Maria Pellisé, Antonio Facciorusso, Cesare Hassan, Alessandro Repici, Roberta Maselli
Journal: Endoscopy (2024)

The gender gap in the authorship of scientific research may affect career advancement. Our aim was to assess the potential gender gap in gastrointestinal (GI) journals.
Biomimetic nanodrug targets inflammation and suppresses YAP/TAZ to ameliorate atherosclerosis
Authors: Hui-Chun Huang, Ting-Yun Wang, Joshua Rousseau, Mark Orlando, Michelle Mungaray, Chamonix Michaud, Christopher Plaisier, Zhen Bouman Chen, Kuei-Chun Wang
Journal: Biomaterials (2024)
Hemostasis — A Balancing Act
Journal: New England Journal of Medicine (2024)

The Perspective article by Bloom, "Learning from the Bomb" (November 30 issue), 1 contains a substantial error.It references a letter from Albert Einstein, stating that Einstein was "pleading with Truman not to authorize use of the atomic bomb."In fact, the cited letter was written to President Franklin Delano Roosevelt in August 1939, long before Harry Truman was even vice president.Furthermore, the letter's text, available online, 2 served only to alert FDR as to the magnitude of atomic energy, its potential for wartime use, and the Hitler regime's interest.Discouraging U.S. investigation or development in this area is not mentioned.Indeed, Einstein encourages FDR toward "quick action" by his administration.Consequently, the Manhattan Project was created to build the bombs destined for use over Japan.
Endoscopic submucosal dissection for early esophageal squamous cell carcinoma: long-term results from a Western cohort
Authors: Ilse N. Beaufort, Charlotte N. Frederiks, Anouk Overwater, Lodewijk A.A. Brosens, Arjun D. Koch, Roos E. Pouw, Jacques J.G.H.M. Bergman, Bas L.A.M. Weusten
Journal: Endoscopy (2024)

Abstract Background Although endoscopic submucosal dissection (ESD) is established as first-choice treatment for early esophageal squamous cell carcinoma (ESCC) worldwide, most data are derived from Asian studies. We aimed to evaluate the long-term outcomes of ESD for patients with early ESCC in a Western cohort. Methods In this retrospective cohort study, patients with early ESCC amenable to ESD were included from four tertiary referral hospitals in the Netherlands between 2012 and 2017. All ESD procedures were performed by experienced endoscopists, after which the decision for additional treatment was made on a per-patient basis. Outcomes were curative resection rate, ESCC-specific survival, and overall survival. Results Of 68 included patients (mean age 69 years; 34 males), ESD was technically successful in 66 (97%; 95%CI 93%–100%), with curative resection achieved in 34/66 (52%; 95%CI 39%–64%). Among patients with noncurative resection, 15/32 (47%) underwent additional treatment, mainly esophagectomy (n = 10) or definitive chemoradiation therapy (n = 4). Endoscopic surveillance was preferred in 17/32 patients (53%), based on severe comorbidities or patient choice. Overall, 31/66 patients (47%) died during a median follow-up of 66 months; 8/31 (26%) were ESCC-related deaths. The 5-year overall and ESCC-specific survival probabilities were 62% (95%CI 52%–75%) and 86% (95%CI 77%–96%), respectively. Conclusion In this Western cohort with long-term follow-up, the effectiveness and safety of ESD for early ESCC was confirmed, although the rate of noncurative resections was substantial. Irrespective of curative status, the long-term prognosis of these patients was limited mainly due to competing mortality.
Cover Image, Volume 44, Issue 1
Authors: Monika Raab, Izabela Kostova, Samuel Peña‐Llopis, Daniela Fietz, Monika Kressin, Seyed Mohsen Aberoumandi, Evelyn Ullrich, Sven Becker, Mourad Sanhaji, Klaus Strebhardt
Journal: Cancer Communications (2024)

The cover image is based on the Original Article Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of highgrade serous ovarian cancer by Monika Raab et al., https://doi.org/10.1002/cac2.12511.
Wet environment-induced adhesion and softening of coenzyme-based polymer elastic patch for treating periodontitis
Authors: Ying Qi, Chenyu Xu, Zhuodan Zhang, Qian Zhang, Ziyang Xu, Xinrui Zhao, Yanhong Zhao, Chunyan Cui, Wenguang Liu
Journal: Bioactive Materials (2024)

Periodontitis, a common chronic inflammatory disease caused by pathogenic bacteria, can be treated with diverse biomaterials by loading drugs, cytokines or proteins. However, these biomaterials often show unsatisfactory therapeutic efficiency due to their poor adhesion, short residence time in the wet and dynamic oral cavity and emerging drug resistance. Here we report a wet-responsive methacrylated gelatin (GelMA)-stabilized co-enzyme polymer poly(α-lipoic acid) (PolyLA)-based elastic patch with water-induced adhesion and softening features. In PolyLA-GelMA, the multiple covalent and hydrogen-bonding crosslinking between PolyLA and GelMA prevent PolyLA depolymerization and slow down the dissociation of PolyLA in water, allowing durable adhesion to oral periodontal tissue and continuous release of LA-based bioactive small molecule in periodontitis wound without resorting external drugs. Compared with the undifferentiated adhesion behavior of traditional adhesives, this wet-responsive patch demonstrates a favorable periodontal pocket insertion ability due to its non-adhesion and rigidity in dry environment. In vitro studies reveal that PolyLA-GelMA patch exhibits satisfactory wet tissue adhesion, antibacterial, blood compatibility and ROS scavenging abilities. In the model of rat periodontitis, the PolyLA-GelMA patch inhibits alveolar bone resorption and accelerates the periodontitis healing by regulating the inflammatory microenvironment. This biomacromolecule-stabilized coenzyme polymer patch provides a new option to promote periodontitis treatment.
The cholera emergency
Authors: None The Lancet Gastroenterology & Hepatology
Journal: The Lancet. Gastroenterology & hepatology (2024)

A year has passed since WHO classified the global resurgence of cholera as a grade 3 emergency—their highest emergency level. Now, in the first situation report of 2024, they provide a fuller picture of the outbreak—there were more than 667 000 cases and 4000 deaths in 2023, surpassing numbers in 2022. Cholera has re-emerged in at least 30 countries. 17 of these are in the WHO African Region, with DR Congo, Zimbabwe, and Sudan reporting around 1000 new cases every week.
Challenges in the diagnosis and treatment of inflammatory bowel disease in Latin America
Authors: Domingo Balderramo, Abel Botelho Quaresma, Pablo A Olivera, Mariane Christina Savio, Maria Paz Gimenez Villamil, Remo Panaccione, Siew C Ng, Gilaad G Kaplan, Paulo Gustavo Kotze
Journal: The Lancet. Gastroenterology & hepatology (2024)
Manufactured scarcity and the allocation of scarce resources
Authors: Mitchell Berger
Journal: The Lancet (2024)

I appreciated the discussion by Ezekiel J Emanuel and Govind Persad,1 but would like to raise three considerations. First, although the authors claim, "A consensus exists on what ethical values are relevant to addressing the challenges of allocating scarce medical resources within and among countries",1 such arguably broad consensus did not always translate into clear and fair prioritisation criteria during the COVID-19 pandemic. For instance, at times during the COVID-19 pandemic, governments and various advisory commissions and panels developed criteria that neglected some individuals most at risk of developing the infection, including people with intellectual or developmental disabilities and mental illness.
Offline: Is there still time?
Authors: Richard Horton
Journal: The Lancet (2024)

"Earth boiled in 2023—will it happen again in 2024?", ran a recent headline in Nature. The question was understandable. 2023 was the hottest year ever recorded. The tone of the article was doom-laden—"climate researchers look ahead with trepidation". Is drenching readers with forecasts of apocalypse the best way to encourage action? Hannah Ritchie does not think so. In Not the End of the World: How We Can Be the First Generation to Build a Sustainable Planet (2024), which runs against the modern tide of catastrophist thinking, Ritchie argues that creating an ambience of anxiety, dread, and pessimism is precisely the wrong way to mobilise society to take climate change (she is no climate denialist) seriously.
Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection
Authors: Gregory W. Albers, Mouhammad Jumaa, Barbara Purdon, Syed F. Zaidi, Christopher Streib, Ashfaq Shuaib, Navdeep Sangha, Minjee Kim, Michael T. Froehler, Neil E. Schwartz, Wayne M. Clark, Charles E. Kircher, Ming Yang, Lori Massaro, Xiao-Yu Lu, Gregory A. Rippon, Joseph P. Broderick, Ken Butcher, Maarten G. Lansberg, David S. Liebeskind, Amre Nouh, Lee H. Schwamm, Bruce C.V. Campbell
Journal: New England Journal of Medicine (2024)

Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P=0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.)
Efficacy of Wolbachia-mediated sterility to reduce the incidence of dengue: a synthetic control study in Singapore
Authors: Jue Tao Lim, Somya Bansal, Chee Seng Chong, Borame Dickens, Youming Ng, Lu Deng, Caleb Lee, Li Yun Tan, Grace Chain, Pei Ma, Shuzhen Sim, Cheong Huat Tan, Alex R Cook, Lee Ching Ng
Journal: The Lancet Microbe (2024)

BackgroundDue to the absence of available therapeutics and good vaccines, vector control solutions are needed to mitigate the spread of dengue. Matings between male Aedes aegypti mosquitoes infected with the wAlbB strain of Wolbachia and wildtype females yield non-viable eggs. We evaluated the efficacy of releasing wAlbB-infected A aegypti male mosquitoes to suppress dengue incidence.MethodsIn this synthetic control study, we conducted large-scale field trials in Singapore involving release of wAlbB-infected A aegypti male mosquitoes for dengue control via vector population suppression, from epidemiological week (EW) 27, 2018, to EW 26, 2022. We selected two large towns (Yishun and Tampines) to adopt an expanding release strategy and two smaller towns (Bukit Batok and Choa Chu Kang) to adopt a targeted-release approach. Releases were conducted two times a week in high-rise public housing estates. All intervention and control locations practised the same baseline dengue control protocol. The main outcome was weekly dengue incidence rate caused by any dengue virus serotype. We used incidence data collected by the Singapore Ministry of Health to assess the efficacy of the interventions. To compare interventions, we used the synthetic control method to generate appropriate counterfactuals for the intervention towns using a weighted combination of 30 control towns between EW 1, 2014 and EW 26, 2022.FindingsOur study comprised an at-risk population of 607 872 individuals living in intervention sites and 3 894 544 individuals living in control sites. Interventions demonstrated up to 77·28% (121/156, 95% CI 75·81–78·58) intervention efficacy despite incomplete coverage across all towns until EW 26, 2022. Intervention efficacies increased as release coverage increased across all intervention sites. Releases led to 2242 (95% CI 2092–2391) fewer cases per 100 000 people in intervention sites during the study period. Secondary analysis showed that these intervention effects were replicated across all age groups and both sexes for intervention sites.InterpretationOur results demonstrated the potential of Wolbachia-mediated incompatible insect technique for strengthening dengue control in tropical cities, where dengue burden is the greatest.FundingSingapore Ministry of Finance, Ministry of Sustainability, and the National Environment Agency, and the Singapore National Robotics Program.
Targeting TACC3 Induces Immunogenic Cell Death and Enhances T-DM1 Response in HER2-Positive Breast Cancer
Authors: Mustafa Emre Gedik, Ozge Saatci, Nathaniel Oberholtzer, Meral Uner, Ozge Akbulut-Caliskan, Metin Cetin, Mertkaya Aras, Kubra Ibis, Burcu Caliskan, Erden Banoglu, Stefan Wiemann, Ayşegül Üner, Sercan Aksoy, Shikhar Mehrotra, Ozgur Sahin
Journal: Cancer Research (2024)

Trastuzumab emtansine (T-DM1) was the first and one of the most successful antibody-drug conjugates (ADC) approved for treating refractory HER2-positive breast cancer. Despite its initial clinical efficacy, resistance is unfortunately common, necessitating approaches to improve response. Here, we found that in sensitive cells, T-DM1 induced spindle assembly checkpoint (SAC)-dependent immunogenic cell death (ICD), an immune-priming form of cell death. The payload of T-DM1 mediated ICD by inducing eIF2α phosphorylation, surface exposure of calreticulin, ATP and HMGB1 release, and secretion of ICD-related cytokines, all of which were lost in resistance. Accordingly, ICD-related gene signatures in pretreatment samples correlated with clinical response to T-DM1-containing therapy, and increased infiltration of antitumor CD8+ T cells in posttreatment samples was correlated with better T-DM1 response. Transforming acidic coiled-coil containing 3 (TACC3) was overexpressed in T-DM1-resistant cells, and T-DM1 responsive patients had reduced TACC3 protein expression whereas nonresponders exhibited increased TACC3 expression during T-DM1 treatment. Notably, genetic or pharmacologic inhibition of TACC3 restored T-DM1-induced SAC activation and induction of ICD markers in vitro. Finally, TACC3 inhibition in vivo elicited ICD in a vaccination assay and potentiated the antitumor efficacy of T-DM1 by inducing dendritic cell maturation and enhancing intratumoral infiltration of cytotoxic T cells. Together, these results illustrate that ICD is a key mechanism of action of T-DM1 that is lost in resistance and that targeting TACC3 can restore T-DM1-mediated ICD and overcome resistance.
Correction: The Primary-Secondary Care Partnership to Improve Outcomes in Chronic Kidney Disease (PSP-CKD) Study: A Cluster Randomized Trial in Primary Care
Journal: Journal of the American Society of Nephrology (2024)

Journal of the American Society of Nephrology ():10.1681/ASN.0000000000000295, February 08, 2024. | DOI: 10.1681/ASN.0000000000000295