tbuckley/cabot-search huggingface dataset:
Lorlatinib Versus Crizotinib in Patients With Advanced <i>ALK</i>-Positive Non–Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study
Authors: Benjamin J. Solomon, Geoffrey Liu, Enriqueta Felip, Tony S.K. Mok, Ross A. Soo, Julien Mazieres, Alice T. Shaw, Filippo de Marinis, Yasushi Goto, Yi-Long Wu, Dong-Wan Kim, Jean-François Martini, Rossella Messina, Jolanda Paolini, Anna Polli, Despina Thomaidou, Francesca Toffalorio, Todd M. Bauer
Journal: Journal of Clinical Oncology (2024)

PURPOSE Lorlatinib improved progression-free survival (PFS) and intracranial activity versus crizotinib in patients with previously untreated, advanced, ALK -positive non–small cell lung cancer (NSCLC) in the phase III CROWN study. Here, we report long-term outcomes from CROWN after 5 years of follow-up. METHODS Two hundred ninety-six patients with ALK -positive NSCLC were randomly assigned 1:1 to receive lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147). This post hoc analysis presents updated investigator-assessed efficacy outcomes, safety, and biomarker analyses. RESULTS With a median follow-up for PFS of 60.2 and 55.1 months, respectively, median PFS was not reached (NR [95% CI, 64.3 to NR]) with lorlatinib and 9.1 months (95% CI, 7.4 to 10.9) with crizotinib (hazard ratio [HR], 0.19 [95% CI, 0.13 to 0.27]); 5-year PFS was 60% (95% CI, 51 to 68) and 8% (95% CI, 3 to 14), respectively. Median time to intracranial progression was NR (95% CI, NR to NR) with lorlatinib and 16.4 months (95% CI, 12.7 to 21.9) with crizotinib (HR, 0.06 [95% CI, 0.03 to 0.12]). Safety profile was consistent with that in prior analyses. Emerging new ALK resistance mutations were not detected in circulating tumor DNA collected at the end of lorlatinib treatment. CONCLUSION After 5 years of follow-up, median PFS has yet to be reached in the lorlatinib group, corresponding to the longest PFS ever reported with any single-agent molecular targeted treatment in advanced NSCLC and across all metastatic solid tumors. These results coupled with prolonged intracranial efficacy and absence of new safety signals represent an unprecedented outcome for patients with advanced ALK -positive NSCLC and set a new benchmark for targeted therapies in cancer.
Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegeneration with an LXR agonist
Authors: Alexandra Litvinchuk, Jung H. Suh, Jing L. Guo, Karin Lin, Sonnet S. Davis, Nga Bien-Ly, Eric Tycksen, G. Travis Tabor, Javier Remolina Serrano, Melissa Manis, Xin Bao, Choonghee Lee, Megan Bosch, Enmanuel J. Perez, Carla M. Yuede, Anil G. Cashikar, Jason D. Ulrich, Gilbert Di Paolo, David M. Holtzman
Journal: Neuron (2024)
N6-methyladenosine-modified SENP1, identified by IGF2BP3, is a novel molecular marker in acute myeloid leukemia and aggravates progression by activating AKT signal via de-SUMOylating HDAC2
Authors: Diguang Wen, Hang Xiao, Yueyi Gao, Hanqing Zeng, Jianchuan Deng
Journal: Molecular Cancer (2024)

Elevated evidence suggests that the SENPs family plays an important role in tumor progression. However, the role of SENPs in AML remains unclear.
Impact and economic analysis of human T-cell lymphotropic virus type 1 (HTLV-1)-targeted antenatal screening, England and Wales, 2021
Authors: Carolina Rosadas, Milene Costa, Kátia Senna, Marisa Santos, Graham P Taylor
Journal: Eurosurveillance (2024)

Background Human T-cell lymphotropic virus type 1 (HTLV-1) is a neglected virus that can cause severe disease and be transmitted from mother to child through breastfeeding. Avoidance of breastfeeding prevents 80% of vertical transmission. The United Kingdom (UK) is currently assessing whether HTLV-1-targeted antenatal screening should be implemented. Aim We aimed to assess the impact and cost-effectiveness of a targeted programme to prevent HTLV-1 vertical transmission in England and Wales. Methods We estimated the number of pregnant women who have high risk of HTLV-1 infection based on their or their partner’s country of birth. With data from 2021, we used a mathematical model to assess cost-effectiveness of HTLV-1 antenatal screening. We also estimated the annual number of infant infections and the number that could be prevented with screening and intervention. Results We estimate that ca 99,000 pregnant women in England and Wales have high risk of HTLV-1 infection. In the absence of screening, 74 (range: 25–211) HTLV-1 infections in infants would be expected to occur every year in England and Wales. Implementation of targeted screening would prevent 58 (range: 19–164) infant infections annually. The intervention is effective (incremental 0.00333 quality-adjusted life years (QALY)) and cost-saving (GBP −57.56 (EUR −66.85)). Conclusion Our findings support implementation of HTLV-1 targeted antenatal screening to reduce vertical transmission from mothers to infants in the UK.
Adapting response to a measles outbreak in a context of high vaccination and breakthrough cases: an example from Vaud, Switzerland, January to March 2024
Authors: Alessandro Cassini, Ludovico Cobuccio, Emmanouil Glampedakis, Pascal Cherpillod, Pierre Alex Crisinel, Francisco-Javier Pérez-Rodríguez, Monica Attinger, Dominique Bachelin, Marie Nahimana Tessemo, Mirjam Maeusezahl, Céline Gardiol, Karim Boubaker
Journal: Eurosurveillance (2024)

A measles outbreak with 51 cases occurred in the canton of Vaud, Switzerland, between January and March 2024. The outbreak was triggered by an imported case, and 37 (72.5%) subsequent cases were previously vaccinated individuals. Epidemiological investigations showed that vaccinated measles cases were symptomatic and infectious. In a highly vaccinated population, it is important to raise awareness among healthcare professionals to suspect and test for measles virus when an outbreak is declared, irrespective of the vaccination status of the patients.
PNPO–PLP axis senses prolonged hypoxia in macrophages by regulating lysosomal activity
Authors: Hiroki Sekine, Haruna Takeda, Norihiko Takeda, Akihiro Kishino, Hayato Anzawa, Takayuki Isagawa, Nao Ohta, Shohei Murakami, Hideya Iwaki, Nobufumi Kato, Shu Kimura, Zun Liu, Koichiro Kato, Fumiki Katsuoka, Masayuki Yamamoto, Fumihito Miura, Takashi Ito, Masatomo Takahashi, Yoshihiro Izumi, Hiroyuki Fujita, Hitoshi Yamagata, Takeshi Bamba, Takaaki Akaike, Norio Suzuki, Kengo Kinoshita, Hozumi Motohashi
Journal: Nature Metabolism (2024)

Abstract Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing systems inducing acute hypoxic responses, including the hypoxia-inducible factor pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here we show that pyridoxine 5′-phosphate oxidase (PNPO), which catalyses bioactivation of vitamin B6, serves as an oxygen sensor and regulates lysosomal activity in macrophages. Decreased PNPO activity under prolonged hypoxia reduced an active form of vitamin B6, pyridoxal 5′-phosphate (PLP), and inhibited lysosomal acidification, which in macrophages led to iron dysregulation, TET2 protein loss and delayed resolution of the inflammatory response. Among PLP-dependent metabolism, supersulfide synthesis was suppressed in prolonged hypoxia, resulting in the lysosomal inhibition and consequent proinflammatory phenotypes of macrophages. The PNPO–PLP axis creates a distinct layer of oxygen sensing that gradually shuts down PLP-dependent metabolism in response to prolonged oxygen deprivation.
Spatial phenotyping of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma
Authors: Sheren Younes, Ajay Subramanian, Anum Khan, Shuchun Zhao, Michael Binkley, Yasodha Natkunam
Journal: Blood Cancer Journal (2024)

Abstract Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma with sparse tumor B-cells and a favorable prognosis. Variant growth patterns of NLPHL, however, often show advanced stage, progression to T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) and a worse prognosis. We studied the tumor microenvironment (TME) of NLPHL and THRLBCL using highplex imaging and spatial profiling at the single cell level. Our findings show distinct differences in TME composition and spatial configuration that differ among typical and variant NLPHL and THRLBCL. Typical NLPHL show abundant helper T-cell subsets, while THRLBCL show abundant cytotoxic T-cells and macrophages. Tumor B-cell size and content is lowest in typical NLPHL, followed by variant NLPHL, and highest in THRLBCL, whereas an opposite trend characterized TME B-cells. CD4/CD8 double-positive T-cells are seen in all NLPHL but not in the majority of THRLBCL and are spatially distant from LP-cells and TFH-rosettes. The differences in macrophage/monocyte content in distinguishing NLPHL pattern E from THRLBCL is further corroborated in independent cohorts of cases. Our results validate the current approach to classification and in addition provide novel insights that could be leveraged to refine clinical management for patients with this spectrum of lymphomas.
Mould allergen Alt a 1 spiked with the micronutrient retinoic acid reduces Th2 response and ameliorates Alternaria allergy in <scp>BALB</scp>/c mice
Authors: Aila Fakhimahmadi, Franziska Roth‐Walter, Gerlinde Hofstetter, Markus Wiederstein, Sebastian A. Jensen, Markus Berger, Nathalie Szepannek, Rodolfo Bianchini, Isabella Pali‐Schöll, Erika Jensen‐Jarolim, Karin Hufnagl
Journal: Allergy (2024)

We investigated the biological function of the mould allergen Alt a 1 as a carrier of micronutrients, such as the vitamin A metabolite retinoic acid (RA) and the influence of RA binding on its allergenicity in vitro and in vivo.
Large hospital outbreak caused by OXA-244-producing Escherichia coli sequence type 38, Poland, 2023
Authors: Radosław Izdebski, Marta Biedrzycka, Paweł Urbanowicz, Dorota Żabicka, Teresa Błauciak, Dorota Lechowicz, Beata Gałecka-Ziółkowska, Marek Gniadkowski
Journal: Eurosurveillance (2024)

In February 2023, Escherichia coli sequence type (ST) 38 producing oxacillinase 244 (OXA-244-Ec ST38) was detected from three patients in a hospital in western Poland. Overall, OXA-244-Ec ST38 was detected from 38 colonised patients in 13 wards between February and June 2023. The outbreak was investigated on site by an infection control team, and the bacterial isolates were characterised microbiologically and by whole genome sequencing. We could not identify the primary source of the outbreak or reconstruct the transmission sequence. In some of the 13 affected wards or their groups linked by the patients’ movement, local outbreaks occurred. The tested outbreak isolates were resistant to β-lactams (penicillins, cephalosporins, aztreonam and ertapenem) and to trimethoprim-sulfamethoxazole. Consistently, apart from bla OXA-244 , all isolates contained also the bla CMY-2 and bla CTX-M-14 genes, coding for an AmpC-like cephalosporinase and extended-spectrum β-lactamase, respectively, and genes conferring resistance to trimethoprim-sulfamethoxazole, sul2 and dfrA1 . Genomes of the isolates formed a tight cluster, not of the major recent European Cluster A but of the older Cluster B, with related isolates identified in Germany. This outbreak clearly demonstrates that OXA-244-Ec ST38 has a potential to cause hospital outbreaks which are difficult to detect, investigate and control.
Queries regarding the two papers each reporting on 1000 essential thrombocythemia patients in BCJ
Authors: Martin H. Ellis
Journal: Blood Cancer Journal (2024)

I read with interest the latest significant contributions of the Florence [1] and Mayo Clinic [2] myeloproliferative neoplasm groups to our understanding of essential thrombocytosis (ET).Their contribution of 1000 patients each, fully annotated and followed for decades, provides unique insights into the disease.I would appreciate additional information and the authors' thoughts regarding the following questions relating to the triple negative (TN) patients in the cohorts:First, was there a group of TN patients who were also negative for all passenger mutations ie who had no clonal marker at all?If so, did they have a different clinical and hematologic phenotype and/or bone marrow histologic findings to the remainder of the TN patients who did have a clonal marker?Second, the TN patients in the Florence cohort seem to have a far better prognosis regarding myelofibrosis, leukemia, and thrombosisfree survival and, to some extent, overall survival too.Could the authors postulate a reason for this, specifically, are these bone fide ET patients given their apparent more "benign course?Finally, the clinical course of the Mayo Clinic TN patients was not as favorable as those from Florence (TN patients fared better only regarding overall survival, leukemia-free survival, and arterial thrombosis-free survival).Do the authors have an explanation for this or are the findings in both cohorts "close enough" to represent an accurate natural TN ET disease course?
Impact of Extraosseous Extramedullary Disease on Outcomes of Patients with Relapsed-Refractory Multiple Myeloma receiving Standard-of-Care Chimeric Antigen Receptor T-Cell Therapy
Authors: Danai Dima, Al-Ola Abdallah, James A. Davis, Hussein Awada, Utkarsh Goel, Aliya Rashid, Shaun DeJarnette, Faiz Anwer, Leyla Shune, Shahzad Raza, Zahra Mahmoudjafari, Louis Williams, Beth Faiman, Joseph P. McGuirk, Craig S. Sauter, Nausheen Ahmed, Jack Khouri, Hamza Hashmi
Journal: Blood Cancer Journal (2024)

Abstract The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T. Responses were assessed per the International Myeloma Working Group criteria. A total of 152 patients proceeded with infusion, of whom 47 (31%) had EMD (EMD group) and 105 (69%) did not (non-EMD group). Baseline patient characteristics were comparable between the two groups. The EMD group had a higher incidence of high-grade CRS, steroid and anakinra use, and thrombocytopenia on day +30 compared to the non-EMD group. In addition, the EMD group had an inferior overall response rate (58% vs 96%, p &lt; 0.00001), median progression-free survival (PFS) (5.1 vs 12.4 months; p &lt; 0.0001), and overall survival (OS) (12.2 vs 27.5 months; p = 0.00058) compared to the non-EMD group. We further subdivided the non-EMD patients into those with paramedullary disease (PMD-only group, n = 26 [17%]) and those with neither EMD nor PMD (bone marrow-contained group or BM-only group, n = 79 [52%]). Patients with PMD-only had similar median PFS (11.2 vs 13.6 months, p = 0.3798) and OS (not reached [NR] vs 27.5 months, p = 0.6446) compared to patients with BM-only disease. However, patients with EMD exhibited inferior median PFS (5.1 vs 13.6 months, p &lt; 0.0001) and OS (12.2 vs 27.5, p = 0.0008) compared to patients in the BM-only group. Treatment with SOC CAR T yielded meaningful clinical outcomes in real-world RRMM patients with extraosseous EMD, though responses and survival outcomes were suboptimal compared to patients without EMD. The presence of only EMD but not PMD was associated with significantly worse survival outcomes following the CAR T infusion.
Imatinib with intensive chemotherapy in AML with t(9;22)(q34.1;q11.2)/BCR::ABL1. A DATAML registry study
Authors: Camille Gondran, Pierre-Yves Dumas, Emilie Bérard, Audrey Bidet, Eric Delabesse, Suzanne Tavitian, Thibaut Leguay, Françoise Huguet, Cécile Borel, Edouard Forcade, François Vergez, Jean-Philippe Vial, Jean Baptiste Rieu, Nicolas Lechevalier, Isabelle Luquet, Alban Canali, Emilie Klein, Audrey Sarry, Anne-Charlotte de Grande, Arnaud Pigneux, Christian Récher, Laetitia Largeaud, Sarah Bertoli
Journal: Blood Cancer Journal (2024)

Abstract Acute myeloid leukemia (AML) with t(9;22) (q34.1; q11.2)/ BCR::ABL1 , a distinct entity within the group of AML with defining genetic abnormalities, belong to the adverse-risk group of the 2022 ELN classification. However, there is little data on outcome since the era of tyrosine kinase inhibitors. Among 5819 AML cases included in the DATAML registry, 20 patients with de novo BCR::ABL1 + AML (0.3%) were identified. Eighteen patients treated with standard induction chemotherapy were analyzed in this study. Imatinib was added to chemotherapy in 16 patients. The female-to-male ratio was 1.25 and median age was 54 years. The t(9;22) translocation was the sole chromosomal abnormality in 12 patients. Main gene mutations detected by NGS were ASXL1 , RUNX1 and NPM1 . Compared with patients with myeloid blast phase of chronic myeloid leukemia (CML-BP), de novo BCR::ABL1 + AML had higher WBC, fewer additional chromosomal abnormalities, lower CD36 or CD7 expression and no ABL1 mutations. Seventeen patients (94.4%) achieved complete remission (CR) or CR with incomplete hematologic recovery. Twelve patients were allografted in first remission. With a median follow-up of 6.3 years, the median OS was not reached and 2-year OS was 77% (95% CI: 50–91). Four out of five patients who were not transplanted did not relapse. Comparison of BCR::ABL1 + AML, CML-BP, 2017 ELN intermediate ( n = 643) and adverse-risk patients ( n = 863) showed that patients with BCR::ABL1 + AML had a significant better outcome than intermediate and adverse-risk patients. BCR::ABL1 + AML patients treated with imatinib and intensive chemotherapy should not be included in the adverse-risk group of current AML classifications.
Treatment of oligo-metastatic pancreatic ductal adenocarcinoma to the liver: is there a role for surgery? A narrative review
Authors: Felice Giuliante, Elena Panettieri, Andrea Campisi, Alessandro Coppola, Maria Vellone, Agostino M. De Rose, Francesco Ardito
Journal: International Journal of Surgery (2024)

Pancreatic ductal adenocarcinoma (PDAC) is a prognostically unfavorable malignancy that presents with distant metastases at the time of diagnosis in half of patients. Even if patients with metastatic PDAC have not been traditionally considered candidates for surgery, an increasing number of researchers have been investigating the efficacy of surgical treatment for patients with liver-only oligometastases from PDAC, showing promising results in extremely selected patients, mainly with metachronous metastases after perioperative chemotherapy. Nevertheless, a standardized definition of oligometastatic disease should be adopted and additional investigations focusing on the role of perioperative chemotherapy and tumor biology are warranted to reliably assess the role of resection for PDAC metastatic to the liver.
In vivo expression of an mRNA encoded multi-mechanistic mAb combination against Staphylococcus aureus and protection in disease model
Authors: Christine Tkaczyk, Michael Newton, Mun Mun Patnaik, George Thom, Martin Strain, Adam Gamson, Olalekan Daramola, Andal Murthy, Julie Douthwaite, Oleg Stepanov, Elin Boger, Haitao Yang, Mark T Esser, Ashley Lidwell, Antonio DiGiandomenico, Luis Santos, Bret R Sellman
Journal: Molecular Therapy (2024)

Single monoclonal antibodies (mAbs) can be expressed in vivo through gene delivery of their mRNA formulated with lipid nanoparticles (LNPs). However, delivery of a mAb combination could be challenging due to the risk of heavy and light variable chain mispairing. We evaluated the pharmacokinetics of a three mAb combination against Staphylococcus aureus first in single chain variable fragment scFv-Fc and then in immunoglobulin G 1 (IgG1) format in mice. Intravenous delivery of each mRNA/LNP or the trio (1 mg/kg each) induced functional antibody expression after 24 h (10-100 μg/mL) with 64%-78% cognate-chain paired IgG expression after 3 days, and an absence of non-cognate chain pairing for scFv-Fc. We did not observe reduced neutralizing activity for each mAb compared with the level of expression of chain-paired mAbs. Delivery of the trio mRNA protected mice in an S. aureus-induced dermonecrosis model. Intravenous administration of the three mRNA in non-human primates achieved peak serum IgG levels ranging between 2.9 and 13.7 μg/mL with a half-life of 11.8-15.4 days. These results suggest nucleic acid delivery of mAb combinations holds promise and may be a viable option to streamline the development of therapeutic antibodies.
Letter to the editor: a commentary on ‘successful robotic kidney transplantation for surgeons with no experience in minimally invasive surgery: a single institution experience’
Authors: Yiqi Huang, Yanling Zhang, Sanmeizi Xie
Journal: International Journal of Surgery (2024)

aDepartment of Nephrology, Shaoxing Second Hospital, Shaoxing, Zhejiang, 312000, China bIntensive Care Unit, Shaoxing Second Hospital, Shaoxing, Zhejiang, 312000, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Intensive Care Unit, Shaoxing Second Hospital, Shaoxing, Zhejiang, 312000, China. E-mail address: [email protected] (S. Xie). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
A commentary on ‘characterization of research trends and prospects on hepatic echinococcosis over the past forty years: a bibliometric analysis’
Authors: Yanlong Shi, Feilong Zhou, Xinhao Li, Fei Jiang
Journal: International Journal of Surgery (2024)

aHepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210003, China bDepartment of General Surgery, Fuyang Hospital of Anhui Medical University, Fuyang, Anhui Province, 236000, China Yanlong Shi, Feilong Zhou, Xinhao Li contributed equally to this work and shared the first authorship. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: No.99, Huangshan Road, Fuyang, Anhui Province, 236000, China. E-mail address: [email protected] (F. Jiang). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Retraction notice to “Liposomal valinomycin mediated cellular K+ leak promoting apoptosis of liver cancer cells” [Journal of Controlled Release 337 (2021) 317–328]
Authors: Qian-Wen Zhang, Mirza Muhammad Faran Ashraf Baig, Tian-Qi Zhang, Ting-Ting Zhai, Xiang Qin, Xing-Hua Xia
Journal: Journal of Controlled Release (2024)
Letter to the Editor: Balancing scientific vigilance and Psychological impact in the management of New COVID-19 variants
Authors: Shidong Wang, Dan Shan
Journal: International Journal of Surgery (2024)

aDepartment of Respiratory Medicine, Shaoxing Second Hospital, Zhejiang, China bClinical Science Institute, University Hospital Galway, Galway, Ireland We declare no competing interests. Not applicable: (Our submission is a letter-to-the-editor) Authorship: Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding Author Address: Clinical Science Institute, University Hospital Galway, Newcastle Road, Galway, H91 YR71, Ireland, Tel: +353 091-495-0743. E-mail address: [email protected] (D. Shan). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/