tbuckley/cabot-search huggingface dataset:
European intersocietal recommendations for the biomarker-based diagnosis of neurocognitive disorders
Authors: Giovanni B Frisoni, Cristina Festari, Federico Massa, Matteo Cotta Ramusino, Stefania Orini, Dag Aarsland, Federica Agosta, Claudio Babiloni, Barbara Borroni, Stefano F Cappa, Kristian S Frederiksen, Lutz Froelich, Valentina Garibotto, Alexander Haliassos, Frank Jessen, Anita Kamondi, Roy PC Kessels, Silvia D Morbelli, John T O'Brien, Markus Otto, Armand Perret-Liaudet, Francesca B Pizzini, Mathieu Vandenbulcke, Ritva Vanninen, Frans Verhey, Meike W Vernooij, Tarek Yousry, Mercè Boada Rovira, Bruno Dubois, Jean Georges, Oskar Hansson, Craig W Ritchie, Philip Scheltens, Wiesje M van der Flier, Flavio Nobili
Journal: The Lancet Neurology (2024)
Monitoring patients with severe traumatic brain injury
Authors: Nicolas Engrand, Loïc Miry
Journal: The Lancet Neurology (2024)

Jean-Francois Payen and colleagues report no differences between combined intracranial pressure and brain tissue oxygen pressure (PbtO2) monitoring versus intracranial pressure monitoring alone on functional outcome 6 months after severe traumatic brain injury.1 This result differs from those of previous studies showing that monitoring PbtO2 in addition to intracranial pressure was more accurate than intracranial pressure alone in detecting cerebral hypoperfusion and improved the prognosis of patients with severe traumatic brain injury.
The predictive value and clinical use of the neurological pupillary index
Authors: Michael TC Poon, Ahmed Nouby, Paul M Brennan
Journal: The Lancet Neurology (2024)

Estimating a patient's outcome after acute brain injury can inform clinical decision-making and support discussions with the patient's family. The objective of the ORANGE study,1 as stated in its protocol, was to predict poor extended Glasgow Outcome Score and mortality using the Neurological Pupil index (NPi); however, the reported analyses assessed the association of NPi with outcomes, not the actual predictive value of the NPi. The proposed NPi pathological threshold of 4 or less is based only on an association with mortality at 6 months in a multivariable Cox regression model.
Targeted delivery of polo-like kinase 1 siRNA nanoparticles using an EGFR-PEG bispecific antibody inhibits proliferation of high-risk neuroblastoma.
Authors: Amy Logan, Christopher B. Howard, Pie Huda, Kathleen Kimpton, Zerong Ma, Kristofer J. Thurecht, Joshua A. McCarroll, Ernest Moles, Maria Kavallaris
Journal: Journal of Controlled Release (2024)
Jaundice with severe leucocytosis
Authors: Sarah Haxhe, Pamela Baldin, Pierre Trefois, Violaine Havelange, Nicolas Lanthier
Journal: Journal of Hepatology (2024)

A 36-year-old Hispanic woman was admitted to the emergency department with jaundice, abdominal pain and fatigue. The patient reported daily alcohol consumption (70 units per week). Physical examination revealed jaundice, hepatosplenomegaly, high BMI (30 kg/m2) and significant bilateral oedema of the lower limbs. Complete blood count showed a severe leucocytosis with neutrophilia (white blood cell count at 48,000/μl including 85% neutrophils) associated with bicytopenia (haemoglobin at 4.3 g/dl and platelet count at 87,000/μl).
The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study
Authors: Nora Schmit, Hillary M Topazian, H Magloire Natama, Duncan Bellamy, Ousmane Traoré, M Athanase Somé, Toussaint Rouamba, Marc Christian Tahita, Massa dit Achille Bonko, Aboubakary Sourabié, Hermann Sorgho, Lisa Stockdale, Samuel Provstgaard-Morys, Jeremy Aboagye, Danielle Woods, Katerina Rapi, Mehreen S Datoo, Fernando Ramos Lopez, Giovanni D Charles, Kelly McCain, Jean-Bosco Ouedraogo, Mainga Hamaluba, Ally Olotu, Alassane Dicko, Halidou Tinto, Adrian V S Hill, Katie J Ewer, Azra C Ghani, Peter Winskill
Journal: The Lancet Infectious Diseases (2024)

The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa.
Activity and safety of enobosarm, a novel, oral, selective androgen receptor modulator, in androgen receptor-positive, oestrogen receptor-positive, and HER2-negative advanced breast cancer (Study G200802): a randomised, open-label, multicentre, multinational, parallel design, phase 2 trial
Authors: Carlo Palmieri, Hannah Linden, Stephen N Birrell, Sally Wheelwright, Elgene Lim, Lee S Schwartzberg, Amy R Dwyer, Theresa E Hickey, Hope S Rugo, Patrick Cobb, Joyce A O'Shaughnessy, Stephen Johnston, Adam Brufsky, Wayne D Tilley, Beth Overmoyer
Journal: The Lancet Oncology (2024)

The androgen receptor is a tumour suppressor in oestrogen receptor-positive breast cancer. The activity and safety of enobosarm, an oral selective androgen receptor modulator, was evaluated in women with oestrogen receptor (ER)-positive, HER2-negative, and androgen receptor (AR)-positive disease.
Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials
Authors: Florian Wagenlehner, Caroline R Perry, Thomas M Hooton, Nicole E Scangarella-Oman, Helen Millns, Marcy Powell, Emily Jarvis, Jeremy Dennison, Amanda Sheets, Deborah Butler, John Breton, Salim Janmohamed
Journal: The Lancet (2024)
Regenerating murine CD8+ lung tissue resident memory T cells after targeted radiation exposure
Authors: Mariah Hassert, Lecia L. Pewe, Rui He, Mohammad Heidarian, Pornpoj Phruttiwanichakun, Stephanie van de Wall, Madison R. Mix, Aliasger K. Salem, Vladimir P. Badovinac, John T. Harty
Journal: The Journal of Experimental Medicine (2024)

Radiation exposure occurs during medical procedures, nuclear accidents, or spaceflight, making effective medical countermeasures a public health priority. Naïve T cells are highly sensitive to radiation-induced depletion, although their numbers recover with time. Circulating memory CD8+ T cells are also depleted by radiation; however, their numbers do not recover. Critically, the impact of radiation exposure on tissue-resident memory T cells (TRM) remains unknown. Here, we found that sublethal thorax-targeted radiation resulted in the rapid and prolonged numerical decline of influenza A virus (IAV)–specific lung TRM in mice, but no decline in antigen-matched circulating memory T cells. Prolonged loss of lung TRM was associated with decreased heterosubtypic immunity. Importantly, boosting with IAV-epitope expressing pathogens that replicate in the lungs or peripheral tissues or with a peripherally administered mRNA vaccine regenerated lung TRM that was derived largely from circulating memory CD8+ T cells. Designing effective vaccination strategies to regenerate TRM will be important in combating the immunological effects of radiation exposure.
Chikungunya seroprevalence, force of infection, and prevalence of chronic disability after infection in endemic and epidemic settings: a systematic review, meta-analysis, and modelling study
Authors: Hyolim Kang, Megan Auzenbergs, Hannah Clapham, Clara Maure, Jong-Hoon Kim, Henrik Salje, Christopher G Taylor, Ahyoung Lim, Andrew Clark, W John Edmunds, Sushant Sahastrabuddhe, Oliver J Brady, Kaja Abbas
Journal: The Lancet Infectious Diseases (2024)
Corrigendum to “3D-printed tri-element-doped hydroxyapatite/ polycaprolactone composite scaffolds with antibacterial potential for osteosarcoma therapy and bone regeneration” [Bioact. Mater. 31 (January 2024) 18–37]
Authors: Hao Huang, Lei Qiang, Minjie Fan, Yihao Liu, Anchun Yang, Dongbiao Chang, Jinsheng Li, Tong Sun, Yiwei Wang, Ruoyi Guo, Hanjie Zhuang, Xiangyu Li, Tailin Guo, Jinwu Wang, Huan Tan, Pengfei Zheng, Jie Weng
Journal: Bioactive Materials (2024)

[This corrects the article DOI: 10.1016/j.bioactmat.2023.07.004.].
Immunotherapy in melanoma: Can we predict response to treatment with circulating biomarkers?
Authors: Elena Splendiani, Zein Mersini Besharat, Alessia Covre, Michele Maio, Anna Maria Di Giacomo, Elisabetta Ferretti
Journal: Pharmacology & Therapeutics (2024)

Melanoma is the most aggressive form of skin cancer, representing approximately 4% of all cutaneous neoplasms it accounts for up to 80% of deaths. Advanced stages of melanoma involve metastatic processes and are associated with high mortality and morbidity, mainly due to the rapid dissemination and heterogeneous responses to current therapies including immunotherapy. Indeed, immune checkpoints inhibitors (ICIs), either alone or in combination with other therapies are currently used in metastatic melanoma (MM) and linked to an increase in patient survival. Of note, the number of therapeutic regimens for MM patients using ICIs has increased, highlighting a growing need for reliable biomarkers that can both predict and monitor response to ICIs. In this context, circulating biomarkers, such as DNA, RNA, proteins, and cells, have emerged due to their ability to detect disease status. Moreover, blood tests are minimally invasive and provide an attractive option to detect biomarkers, avoiding stressful medical procedures. This systematic review summarizes of this review is to evaluate the possibility of a non-invasive biomarker signature that can guide therapeutic decisions. The studies reported here offer valuable insight into how circulating biomarkers can have a role personalized treatments for melanoma patients receiving ICIs therapy, emphasizing the need for rigorous clinical trials to confirm findings and establish standardized procedures.
Self‐Assembly of 2D Polyphthalocyanine in Lysosome Enables Multienzyme Activity Enhancement to Induce Tumor Ferroptosis
Authors: Mingjie Rong, Jian Liu, Lehui Lu
Journal: Advanced Healthcare Materials (2024)

Abstract Nanozymes show great potential in facilitating tumor ferroptosis by upregulation of reactive oxygen species (ROS) and downregulation of glutathione (GSH). However, mild acidity (pH 6.5–6.9) of tumor microenvironment severely restricts the activity of nanozymes. Although lysosomes as acidic organelles (pH = 3.5–5.5) are hopeful for improving enzyme‐like activity, most reported nanozymes are not capable of effectively accumulating in the lysosomes. Herein, an acid‐responsive self‐assembly strategy based on iron phthalocyanine‐rich covalent organic framework nanosheets (COF FePc NSs) is developed, which enables lysosomal targeting aggregation of COF FePc NSs due to the existence of abundant negative hydroxyl groups and rigid structure. Meanwhile, COF FePc NSs display exceptional multienzyme‐mimic performance at lower pH to efficiently generate ROS to cause lysosome damage and apoptosis by synergistic photothermal effect. Subsequently, the released COF FePc with GSH oxidase‐mimicking activity can consume GSH to promote ferroptosis. This is the first report of a 2D COF using its own properties to achieve lysosomal self‐assembly. Overall, the work provides a new paradigm for the development of lysosome‐targeted nanosystems.
Effect of parental touch on relieving acute procedural pain in neonates and parental anxiety (Petal): a multicentre, randomised controlled trial in the UK
Authors: Annalisa G V Hauck, Marianne van der Vaart, Eleri Adams, Luke Baxter, Aomesh Bhatt, Daniel Crankshaw, Amraj Dhami, Ria Evans Fry, Marina B O Freire, Caroline Hartley, Roshni C Mansfield, Simon Marchant, Vaneesha Monk, Fiona Moultrie, Mariska Peck, Shellie Robinson, Jean Yong, Ravi Poorun, Maria M Cobo, Rebeccah Slater
Journal: The Lancet Child & Adolescent Health (2024)

Touch interventions such as massage and skin-to-skin contact relieve neonatal pain. The Parental touch trial (Petal) aimed to assess whether parental stroking of their baby before a clinically required heel lance, at a speed of approximately 3 cm/s to optimally activate C-tactile nerve fibres, provides effective pain relief.
Z-Scores or Fixed Cut-Off Values to Interpret Oscillometry: Opportunities from the LEAD Study
Authors: Sundeep Salvi, Deesha Ghorpade
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Z-Scores or Fixed Cut-Off Values to Interpret Oscillometry: Opportunities from the LEAD Study." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Decoding Serine Metabolism: Unveiling Novel Pathways for Evolving Cancer Therapies
Authors: Aristotle Lau, John Blenis, Guillermo Burgos-Barragan
Journal: Cancer Research (2024)

Serine metabolism plays a pivotal role in cancer, making it an appealing therapeutic target. Two recent studies published in Nature Metabolism and Science Translational Medicine uncovered novel players and therapeutic opportunities within this crucial metabolic pathway. Papalazarou and colleagues employed genetic tools coupled with metabolomics and high-throughput imaging to identify and characterize membrane transporters involved in serine uptake and mitochondrial import in colorectal cancer. Notably, they showed that dual inhibition of these transporters in combination with impaired serine biosynthesis reduced tumor growth in xenograft models. In a parallel study, Zhang and colleagues identified isocitrate dehydrogenase I (IDH1) as a novel regulator of serine biosynthesis in non–small cell lung cancer. Through extensive mechanistic studies, they demonstrated that IDH1 enhances the expression of the key enzymes phosphoglycerate dehydrogenase and phosphoserine aminotransferase 1 via a noncanonical function independent of its enzymatic activity. Strikingly, pharmacologic disruption of this novel function of IDH1 not only diminished tumor growth but also enhanced the anticancer efficacy of dietary serine restriction in mouse models of lung cancer. Together, these studies advance our mechanistic understanding of how cancer cells fulfill their serine requirements and reveal innovative therapeutic avenues to deprive tumors of this vital nutrient.
A quantitative systems pharmacology workflow toward optimal design and biomarker stratification of atopic dermatitis clinical trials
Authors: Natacha Go, Simon Arsène, Igor Faddeenkov, Théo Galland, Shiny Martis B., Diane Lefaudeux, Yishu Wang, Loic Etheve, Evgueni Jacob, Claudio Monteiro, Jim Bosley, Caterina Sansone, Christian Pasquali, Lorenz Lehr, Alexander Kulesza
Journal: Journal of Allergy and Clinical Immunology (2024)
When I use a word . . . Medical blue plaques in London
Authors: Jeffrey K Aronson
Journal: BMJ (2024)

In 1863 the MP William Ewart suggested that “it might be practicable... to have inscribed on those houses in London which have been inhabited by celebrated persons, the names of such persons.” Accordingly, in 1867 the first such inscriptions, which came to be known as blue plaques, were put up by the Society of Arts, commemorating Lord Byron and Napoleon III at places in London where they had lived. The society put up 35 such plaques over the next 35 years when the scheme was taken over by the London County Council, which gave way to the Greater London Council in 1965 and finally English Heritage, in 1986. Among London’s 1000 or so blue plaques several medical men and women, doctors, nurses, and other healthcare workers, are commemorated. They include Cecil Belfield-Clarke, Hannah Billig, Richard Bright, Edith Louisa Cavell, Henry Hallett Dale, Charles Darwin, Henry Havelock Ellis, Elizabeth Garrett Anderson, Thomas Hodgkin, William Hunter and his brother John, Joseph Lister, James Mackenzie, Rachel McMillan and her sister Margaret, William Marsden, Florence Nightingale, Ronald Ross, Mary Seacole, Hans Sloane, and George Frederick Still.
Association Between Neighborhood Opportunity, Allostatic Load, and All-Cause Mortality in Patients With Breast Cancer
Authors: J.C. Chen, Mohamed I. Elsaid, Demond Handley, Jesse J. Plascak, Barbara L. Andersen, William E. Carson, Timothy M. Pawlik, Naleef Fareed, Samilia Obeng-Gyasi
Journal: Journal of Clinical Oncology (2024)

PURPOSE Adverse neighborhood contextual factors may affect breast cancer outcomes through environmental, psychosocial, and biological pathways. The objective of this study is to examine the relationship between allostatic load (AL), neighborhood opportunity, and all-cause mortality among patients with breast cancer. METHODS Women age 18 years and older with newly diagnosed stage I-III breast cancer who received surgical treatment between January 1, 2012, and December 31, 2020, at a National Cancer Institute Comprehensive Cancer Center were identified. Neighborhood opportunity was operationalized using the 2014-2018 Ohio Opportunity Index (OOI), a composite measure derived from neighborhood level transportation, education, employment, health, housing, crime, and environment. Logistic and Cox regression models tested associations between the OOI, AL, and all-cause mortality. RESULTS The study cohort included 4,089 patients. Residence in neighborhoods with low OOI was associated with high AL (adjusted odds ratio, 1.21 [95% CI, 1.05 to 1.40]). On adjusted analysis, low OOI was associated with greater risk of all-cause mortality (adjusted hazard ratio [aHR], 1.45 [95% CI, 1.11 to 1.89]). Relative to the highest (99th percentile) level of opportunity, risk of all-cause mortality steeply increased up to the 70th percentile, at which point the rate of increase plateaued. There was no interaction between the composite OOI and AL on all-cause mortality ( P = .12). However, there was a higher mortality risk among patients with high AL residing in lower-opportunity environments (aHR, 1.96), but not in higher-opportunity environments (aHR, 1.02; P interaction = .02). CONCLUSION Lower neighborhood opportunity was associated with higher AL and greater risk of all-cause mortality among patients with breast cancer. Additionally, environmental factors and AL interacted to influence all-cause mortality. Future studies should focus on interventions at the neighborhood and individual level to address socioeconomically based disparities in breast cancer.
Response of a Novel KANK1::ALK Fusion to Alectinib in an Advanced Lung Adenocarcinoma: A Case Report
Authors: Quanying Tang, Tong Li, Fan Ren, Xuanguang Li, WeiBo Cao, Haochuan Yu, Fuling Mao, Cancan Cao, Lingling Zu, Song Xu
Journal: Journal of the National Comprehensive Cancer Network (2024)

More than 90 distinct fusion partners of ALK rearrangement have been identified. Different ALK fusions may exhibit different sensitivities to ALK tyrosine kinase inhibitors. The emergence of rare fusions poses significant challenges to targeted therapies. This study aimed to investigate the response of KANK1::ALK fusion to alectinib in an advanced lung adenocarcinoma. A novel KANK1::ALK fusion was identified by next-generation sequencing (NGS) and Ventana immunohistochemistry assessments. A 73-year-old woman who had never smoked was admitted with hemoptysis in May 2020. PET/CT revealed a nodule in the left upper lobe, with bilateral pulmonary and multiple lymph node metastases. The upper lobe nodule of the left lung was diagnosed as adenocarcinoma through bronchofiberscopy biopsy, resulting in a clinical diagnosis of stage IVA (cT1c,N3,M1a). Because the biopsy tissue was insufficient for NGS analysis, a blood-based genetic analysis was performed, revealing the presence of KRAS p.Q61R mutations. The patient received carboplatin and pemetrexed with pembrolizumab as first-line therapy, followed by maintenance therapy of pembrolizumab monotherapy. Although the tumor initially showed significant shrinkage, it unfortunately progressed further after 11 months. Subsequently, the patient was given carboplatin and pemetrexed with pembrolizumab again, but the tumor progression continued. An NGS using a rebiopsy of the left upper lobe tumor suggested a KANK1::ALK fusion. Alectinib was prescribed in January 2022, and a durable partial response was observed after 18 months. ALK rearrangements were observed in the broader spectrum of lung cancers. This study provided a potential treatment option for patients with KANK1::ALK fusions. Further studies are needed to understand the function of these fusions.
Impact of Pain on Symptom Burden in Chemotherapy-Induced Peripheral Neurotoxicity
Authors: Fawaz Mayez Mahfouz, Tiffany Li, Hannah C. Timmins, Lisa G. Horvath, Michelle Harrison, Peter Grimison, Gavin Marx, David Goldstein, Susanna B. Park
Journal: Journal of the National Comprehensive Cancer Network (2024)

Chemotherapy-induced peripheral neurotoxicity (CIPN) affects the quality of life of cancer survivors. However, the impact of pain on symptom burden remains undefined. This study aimed to define differences in the clinical symptom profile of patients with painful and nonpainful CIPN.
<i>let-7</i> miRNAs repress HIC2 to regulate BCL11A transcription and hemoglobin switching
Authors: Peng Huang, Scott A. Peslak, Vanessa Shehu, Cheryl A. Keller, Belinda Giardine, Junwei Shi, Ross C. Hardison, Gerd A. Blobel, Eugene Khandros
Journal: Blood (2024)
The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease
Authors: Rowan O. Brothers, Katherine B. Turrentine, Mariam Akbar, Sydney Triplett, Hongting Zhao, Tara M. Urner, Adam Goldman-Yassen, Richard A. Jones, Jack Knight-Scott, Sarah S. Milla, Shasha Bai, Amy Tang, R. Clark Brown, Erin M. Buckley
Journal: Blood (2024)

Abstract Voxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy combined with diffuse correlation spectroscopy were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume, and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin–labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA aged 8 to 18 years. CBFi was significantly positively correlated with ASL-MRI–measured blood flow (R2 = 0.651; P = .015). Next, a single-center, open-label pilot study was completed in 8 children with SCA aged 4 to 17 years on voxelotor, monitored before treatment initiation and at 4, 8, and 12 weeks (NCT05018728). By 4 weeks, both OEF and CBFi significantly decreased, and these decreases persisted to 12 weeks (both P &amp;lt; .05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin (Hb) concentration (P = .025), whereas the correlation between decreases in OEF and increases in Hb trended toward significance (P = .12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared with controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments. This trial was registered at www.ClinicalTrials.gov as #NCT05018728.