tbuckley/cabot-search huggingface dataset:
Privacy preserving image registration
Authors: Riccardo Taiello, Melek Önen, Francesco Capano, Olivier Humbert, Marco Lorenzi
Journal: Medical Image Analysis (2024)

Image registration is a key task in medical imaging applications, allowing to represent medical images in a common spatial reference frame. Current approaches to image registration are generally based on the assumption that the content of the images is usually accessible in clear form, from which the spatial transformation is subsequently estimated. This common assumption may not be met in practical applications, since the sensitive nature of medical images may ultimately require their analysis under privacy constraints, preventing to openly share the image content. In this work, we formulate the problem of image registration under a privacy preserving regime, where images are assumed to be confidential and cannot be disclosed in clear. We derive our privacy preserving image registration framework by extending classical registration paradigms to account for advanced cryptographic tools, such as secure multi-party computation and homomorphic encryption, that enable the execution of operations without leaking the underlying data. To overcome the problem of performance and scalability of cryptographic tools in high dimensions, we propose several techniques to optimize the image registration operations by using gradient approximations, and by revisiting the use of homomorphic encryption trough packing, to allow the efficient encryption and multiplication of large matrices. We focus on registration methods of increasing complexity, including rigid, affine, and non-linear registration based on cubic splines or diffeomorphisms parameterized by time-varying velocity fields. In all these settings, we demonstrate how the registration problem can be naturally adapted for accounting to privacy-preserving operations, and illustrate the effectiveness of PPIR on a variety of registration tasks.
Characteristics and incidence of infections in patients with multiple myeloma treated by bispecific antibodies: a national retrospective study
Authors: Aurélie Jourdes, Elise Cellerin, Cyrille Touzeau, Stéphanie Harel, Blandine Denis, Guillaume Escure, Emmanuel Faure, Simon Jamard, Francois Danion, Cécile Sonntag, Florence Ader, Lionel Karlin, Sarah Soueges, Clarisse Cazelles, Clémentine de La Porte des Vaux, Laurent Frenzel, Fanny Lanternier, Xavier Brousse, Titouan Cazaubiel, Pierre Berger, Aude Collignon, Mathieu Blot, Andrea Pieragostini, Morgane Charles, Carine Chaleteix, Alexis Redor, Virginie Roland, Tom Cartau, Margaret Macro, Thomas Chalopin, Nicolas Vallet, Aurore Perrot, Guillaume Martin-Blondel
Journal: Clinical Microbiology and Infection (2024)

Bispecific antibodies (BsAbs) are an effective treatment used in relapsed or refractory multiple myeloma. Despite a well-tolerated safety profile, infectious events appear to be frequent in clinical trials. Real-world data on epidemiology, characteristics, risk factors, and outcomes of infections in patients treated with BsAb are still needed. A retrospective, multicentre study in BsAb-treated patients with multiple myeloma was performed in 14 French centres from December 2020 to February 2023. The primary objective was to describe the incidence of infections that required hospitalization, specific treatment, or adaptation in BsAb administration. Among 229 patients with multiple myeloma treated with BsAb, 153 (67%) received teclistamab, 47 (20%) received elranatamab, and 29 (13%) talquetamab. We reported a total of 234 infections, including 123 (53%) of grade of ≥3. Predominant infections affected the respiratory tract (n = 116, 50%) followed by bacteraemias (n = 36, 15%). The hospitalization rate was 56% (n = 131), and 20 (9%) infections resulted in death. Global cumulative incidence of the first infection was 70% in all patients, 73% in patients treated with B-cell maturation antigen-targeting, and 51% with GPRC5D-targeting BsAb. In univariate analyses, corticosteroids for cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with a higher risk of first infection (HR = 2.13; 95% CI, 1.38-3.28), whereas GPRC5D-targeting BsAb and anti-bacterial prophylaxis were associated with a lower risk (HR = 0.53; 95% CI, 0.3-0.94 and HR = 0.65; 95% CI, 0.46-0.9). Fine and Gray multivariate model found that only corticosteroids for CRS/ICANS were correlated with a higher risk of first infection (HR = 2.01; 95% CI, 1.27-3.19). The implementation of preventive measures that aim to mitigate the risk of infection under BsAb is pivotal, notably in patients who received corticosteroids for CRS/ICANS.
Expanding the repertoire reveals recurrent, cryptic, and hematopoietic HLA class I minor histocompatibility antigens
Authors: Kyra J. Fuchs, Marian van de Meent, M. Willy Honders, Indu Khatri, Michel G. D. Kester, Eva A. S. Koster, Georgia Koutsoumpli, Arnoud H. de Ru, Cornelis A. M. van Bergen, Peter A. van Veelen, Peter A. C. ’t Hoen, Peter van Balen, Erik B. van den Akker, J. Hendrik Veelken, Constantijn J. M. Halkes, J. H. Frederik Falkenburg, Marieke Griffioen
Journal: Blood (2024)

Abstract Allogeneic stem cell transplantation (alloSCT) is a curative treatment for hematological malignancies. After HLA-matched alloSCT, antitumor immunity is caused by donor T cells recognizing polymorphic peptides, designated minor histocompatibility antigens (MiHAs), that are presented by HLA on malignant patient cells. However, T cells often target MiHAs on healthy nonhematopoietic tissues of patients, thereby inducing side effects known as graft-versus-host disease. Here, we aimed to identify the dominant repertoire of HLA-I-restricted MiHAs to enable strategies to predict, monitor or modulate immune responses after alloSCT. To systematically identify novel MiHAs by genome-wide association screening, T-cell clones were isolated from 39 transplanted patients and tested for reactivity against 191 Epstein-Barr virus transformed B cell lines of the 1000 Genomes Project. By discovering 81 new MiHAs, we more than doubled the antigen repertoire to 159 MiHAs and demonstrated that, despite many genetic differences between patients and donors, often the same MiHAs are targeted in multiple patients. Furthermore, we showed that one quarter of the antigens are cryptic, that is translated from unconventional open reading frames, for example long noncoding RNAs, showing that these antigen types are relevant targets in natural immune responses. Finally, using single cell RNA-seq data, we analyzed tissue expression of MiHA-encoding genes to explore their potential role in clinical outcome, and characterized 11 new hematopoietic-restricted MiHAs as potential targets for immunotherapy. In conclusion, we expanded the repertoire of HLA-I-restricted MiHAs and identified recurrent, cryptic and hematopoietic-restricted antigens, which are fundamental to predict, follow or manipulate immune responses to improve clinical outcome after alloSCT.
Biomarker-based staging of Alzheimer disease: rationale and clinical applications
Authors: Joseph Therriault, Suzanne E. Schindler, Gemma Salvadó, Tharick A. Pascoal, Andréa Lessa Benedet, Nicholas J. Ashton, Thomas K. Karikari, Liana Apostolova, Melissa E. Murray, Inge Verberk, Jacob W. Vogel, Renaud La Joie, Serge Gauthier, Charlotte Teunissen, Gil D. Rabinovici, Henrik Zetterberg, Randall J. Bateman, Philip Scheltens, Kaj Blennow, Reisa Sperling, Oskar Hansson, Clifford R. Jack, Pedro Rosa-Neto
Journal: Nature Reviews Neurology (2024)
Is the T2MR Candida Panel a suitable alternative to the SeptiFast for the rapid diagnosis of candidemia in routine clinical practice?
Authors: Iris Camp, Astrid Füszl, Brigitte Selitsch, Ivonne Kröckel, Katharina Kovac, Martin Wahrmann, Barbara Steinlechner, Johannes Weber, Peter Schellongowski, Christian Zauner, Guerkan Sengölge, Tamara Seitz, Alexander Zoufaly, Barbara Ströbele, Stefan Fuchs, Cornelia Lass-Flörl, Heinz Burgmann, Michael Kundi, Birgit Willinger
Journal: Clinical Microbiology and Infection (2024)

Objectives The diagnosis of invasive Candida infection remains challenging due to tests with slow turnaround times or mediocre performance. T2MR is a new diagnostic tool. We investigated the diagnostic accuracy of the T2Candida® panel (T2) in comparison to blood culture (BC) and the SeptiFast® (SF) for the detection of five different Candida species among high-risk ICU patients with suspected candidemia. Methods We analysed blood samples collected from patients with suspected candidemia (177 samples from 138 patients) from August 2018 to April 2020. Blood samples were collected and analysed concurrently by BC, SF and T2Candida®. Subsequently – based on clinical and microbiological findings – patient samples were assigned to specific risk categories (proven, probable, no candidemia). Results Twenty-two samples from 17 patients were classified as proven candidemia, and 15 samples from 14 patients were classified as probable candidemia. A sensitivity of 68.2% (95% CI 45∼86%) was observed for the BC and the SF, and a sensitivity of 63.6% (95% CI 41∼83%) was observed for the T2 when only cases with proven candidemia were evaluated. For proven & probable candidemia, the sensitivity was 40.5% (95% CI 23∼58) for BC, 81.1% (95% CI 65∼92%) for SF and 73.0% (95% CI 56∼86%) for T2. Conclusions The diagnostic performance of SF and T2 was similar. For samples with proven/probable candidemia, SF and T2 had a higher sensitivity compared to BC. Used in conjunction with other diagnostic methods, T2 can replace the no longer available SF for the diagnosis of candidemia, enabling the timely initiation of a targeted antifungal therapy.
Global burden of early-onset osteoarthritis, 1990–2019: results from the Global Burden of Disease Study 2019
Authors: Qianlin Weng, Qiu Chen, Ting Jiang, Yuqing Zhang, Weiya Zhang, Michael Doherty, Junqing Xie, Ke Liu, Jiatian Li, Tuo Yang, Jie Wei, Guanghua Lei, Chao Zeng
Journal: Annals of the Rheumatic Diseases (2024)

Early-onset osteoarthritis (OA) is an emerging health issue amidst the escalating prevalence of overweight and obesity. However, there are scant data on its disease, economic burden and attributable burden due to high body mass index (BMI).
Platelet dysfunction reversal with cold-stored vs room temperature–stored platelet transfusions
Authors: Valery J. Kogler, Jeffrey A. Miles, Tahsin Özpolat, S. Lawrence Bailey, Daire A. Byrne, Morgan Bawcom-Randall, Yi Wang, Hannah J. Larsen, Franklin Reed, Xiaoyun Fu, Moritz Stolla
Journal: Blood (2024)

Platelets are stored at room temperature for 5 to 7 days (room temperature-stored platelets [RSPs]). Because of frequent and severe shortages, the US Food and Drug Administration recently approved up to 14-day cold-stored platelets (CSPs) in plasma. However, the posttransfusion function of CSPs is unknown and it is unclear which donors are best suited to provide either RSPs or CSPs. In this study, we sought to evaluate the posttransfusion platelet function and its predictors for platelets stored for the maximum approved storage times (7-day RSPs and 14-day CSPs) in healthy volunteers on acetylsalicylic acid (ASA). We conducted a randomized crossover study in 10 healthy humans. Individuals donated 1 platelet unit, stored at either 22°C or 4°C based on randomization. Before transfusion, participants ingested ASA to inhibit endogenous platelets. Transfusion recipients were tested for platelet function and lipid mediators. Platelet units were tested for lipid mediators only. A second round of transfusion with the alternative product was followed by an identical testing sequence. RSPs reversed platelet inhibition significantly better in αIIbβ3 integrin activation-dependent assays. In contrast, CSPs in recipients led to significantly more thrombin generation, which was independent of platelet microparticles. Lysophosphatidylcholine-O species levels predicted the procoagulant capacity of CSPs. In contrast, polyunsaturated fatty acid concentrations predicted the aggregation response of RSPs. In summary, we provide, to our knowledge, the first efficacy data of extended-stored CSPs in plasma. Our results suggest that identifying ideal RSP and CSP donors is possible, and pave the way for larger studies in the future. This trial is registered at www.ClinicalTrials.gov as #NCT0511102.
Combining TIGIT Blockade with MDSC Inhibition Hinders Breast Cancer Bone Metastasis by Activating Antitumor Immunity
Authors: Lea Monteran, Nour Ershaid, Ye’ela Scharff, Yazeed Zoabi, Tamer Sanalla, Yunfeng Ding, Anna Pavlovsky, Yael Zait, Marva Langer, Tal Caller, Anat Eldar-Boock, Camila Avivi, Amir Sonnenblick, Ronit Satchi-Fainaro, Iris Barshack, Noam Shomron, Xiang H.-F. Zhang, Neta Erez
Journal: Cancer Discovery (2024)

Bone is the most common site of breast cancer metastasis. Bone metastasis is incurable and is associated with severe morbidity. Utilizing an immunocompetent mouse model of spontaneous breast cancer bone metastasis, we profiled the immune transcriptome of bone metastatic lesions and peripheral bone marrow at distinct metastatic stages, revealing dynamic changes during the metastatic process. We show that cross-talk between granulocytes and T cells is central to shaping an immunosuppressive microenvironment. Specifically, we identified the PD-1 and TIGIT signaling axes and the proinflammatory cytokine IL1β as central players in the interactions between granulocytes and T cells. Targeting these pathways in vivo resulted in attenuated bone metastasis and improved survival, by reactivating antitumor immunity. Analysis of patient samples revealed that TIGIT and IL1β are prominent in human bone metastasis. Our findings suggest that cotargeting immunosuppressive granulocytes and dysfunctional T cells may be a promising novel therapeutic strategy to inhibit bone metastasis. Significance: Temporal transcriptome profiling of the immune microenvironment in breast cancer bone metastasis revealed key communication pathways between dysfunctional T cells and myeloid derived suppressor cells. Cotargeting of TIGIT and IL1β inhibited bone metastasis and improved survival. Validation in patient data implicated these targets as a novel promising approach to treat human bone metastasis.
Aneuploidy Can Be an Evolutionary Diversion on the Path to Adaptation
Authors: Ilia Kohanovski, Martin Pontz, Pétra Vande Zande, Anna Selmecki, Orna Dahan, Yitzhak Pilpel, Avihu H Yona, Yoav Ram
Journal: Molecular Biology and Evolution (2024)

Abstract Aneuploidy is common in eukaryotes, often leading to decreased fitness. However, evidence from fungi and human tumur cells suggests that specific aneuploidies can be beneficial under stressful conditions and facilitate adaptation. In a previous evolutionary experiment with yeast, populations evolving under heat stress became aneuploid, only to later revert to euploidy after beneficial mutations accumulated. It was therefore suggested that aneuploidy is a “stepping stone” on the path to adaptation. Here, we test this hypothesis. We use Bayesian inference to fit an evolutionary model with both aneuploidy and mutation to the experimental results. We then predict the genotype frequency dynamics during the experiment, demonstrating that most of the evolved euploid population likely did not descend from aneuploid cells, but rather from the euploid wild-type population. Our model shows how the beneficial mutation supply—the product of population size and beneficial mutation rate–determines the evolutionary dynamics: with low supply, much of the evolved population descends from aneuploid cells; but with high supply, beneficial mutations are generated fast enough to outcompete aneuploidy due to its inherent fitness cost. Our results suggest that despite its potential fitness benefits under stress, aneuploidy can be an evolutionary “diversion” rather than a “stepping stone”: it can delay, rather than facilitate, the adaptation of the population, and cells that become aneuploid may leave less descendants compared to cells that remain diploid.
Smartphone keyboard dynamics predict affect in suicidal ideation
Authors: Loran Knol, Anisha Nagpal, Imogen E. Leaning, Elena Idda, Faraz Hussain, Emma Ning, Tory A. Eisenlohr-Moul, Christian F. Beckmann, Andre F. Marquand, Alex Leow
Journal: npj Digital Medicine (2024)

Abstract While digital phenotyping provides opportunities for unobtrusive, real-time mental health assessments, the integration of its modalities is not trivial due to high dimensionalities and discrepancies in sampling frequencies. We provide an integrated pipeline that solves these issues by transforming all modalities to the same time unit, applying temporal independent component analysis (ICA) to high-dimensional modalities, and fusing the modalities with linear mixed-effects models. We applied our approach to integrate high-quality, daily self-report data with BiAffect keyboard dynamics derived from a clinical suicidality sample of mental health outpatients. Applying the ICA to the self-report data (104 participants, 5712 days of data) revealed components related to well-being, anhedonia, and irritability and social dysfunction. Mixed-effects models (55 participants, 1794 days) showed that less phone movement while typing was associated with more anhedonia (β = −0.12, p = 0.00030). We consider this method to be widely applicable to dense, longitudinal digital phenotyping data.
Measuring patient’s effort on the ventilator
Authors: Rodrigo Cornejo, Irene Telias, Laurent Brochard
Journal: Intensive Care Medicine (2024)

Allowing spontaneous breathing with optimal inspiratory effort should be a priority in patients with acute respiratory failure under mechanical ventilation.Low and absent effort promote diaphragmatic dysfunction, creating difficulties in weaning, but also atelectasis and hypoxemia, while intense inspiratory efforts generate negative alveolar pressures and can induce lung (i.e., patient selfinflicted lung injury-P-SILI) and diaphragmatic injury (myotrauma) [1].Low effort even occurs despite apparently spontaneous "triggered" breaths, because assisted ventilation deliver minimal minute ventilation once triggered.The transition from controlled to assisted ventilation can be associated with vigorous efforts in patients with hypoxemic failure, difficult to control [2].In addition, lung injury and systemic inflammation are primers for P-SILI and myotrauma with excessive concentric or eccentric loading [1,3].Mechanisms of P-SILI include excessive global and regional lung stress (due to pendelluft) and increased transvascular pressure, and are directly associated with the magnitude and timing of inspiratory effort [3,4].There is also evidence of interaction between lung and other organs such as brain and kidneys.Therefore, monitoring respiratory drive and effort to adjust ventilatory settings and sedation seems necessary to achieve lung-and diaphragm-protective targets that should result in better clinical outcomes.This review describes the tools and the different parameters for monitoring respiratory effort, and suggests targets for respiratory drive and effort (Fig. 1).
New systemic treatment paradigms in resectable non-small cell lung cancer and variations in patient access across Europe
Authors: Ilias Houda, Chris Dickhoff, Carin A. Uyl-de Groot, Noemi Reguart, Mariano Provencio, Antonin Levy, Rafal Dziadziuszko, Cecilia Pompili, Massimo Di Maio, Michael Thomas, Alessandro Brunelli, Sanjay Popat, Suresh Senan, Idris Bahce
Journal: The Lancet Regional Health - Europe (2024)

The treatment landscape of resectable early-stage non-small cell lung cancer (NSCLC) is set to change significantly due to encouraging results from randomized trials evaluating neoadjuvant and adjuvant immunotherapy, as well as adjuvant targeted therapy. As of January 2024, marketing authorization has been granted for four new indications in Europe, and regulatory approvals for other study regimens are expected. Because cost-effectiveness and reimbursement criteria for novel treatments often differ between European countries, access to emerging developments may lead to inequalities due to variations in recommended and available lung cancer care throughout Europe. This Series paper (i) highlights the clinical studies reshaping the treatment landscape in resectable early-stage NSCLC, (ii) compares and contrasts approaches taken by the European Medicines Agency (EMA) for drug approval to that taken by the United States Food and Drug Administration (FDA), and (iii) evaluates the differences in access to emerging treatments from an availability perspective across European countries.
Abstract B035: A compendium of syngeneic, transplantable pediatric high-grade glioma models reveals subtype-specific therapeutic vulnerabilities
Authors: Michael McNicholas, Antonella De Cola, Zahedeh Bashardanesh, Amelia Foss, Cameron Lloyd, Steven Hebert, Damien Faury, Augusto Faria Andrade, Nada Jabado, Claudia Kleinman, Manav Pathania
Journal: Cancer Research (2024)

Abstract Pediatric high-grade gliomas (pHGGs) are lethal, incurable brain tumors frequently driven by clonal mutations in histone genes. They often harbor a range of additional genetic alterations that correlate with different ages, anatomical locations, and tumor subtypes. We developed models representing 16 pHGG subtypes driven by different combinations of alterations targeted to specific brain regions. Tumors developed with varying latencies and cell lines derived from these models engrafted in syngeneic, immunocompetent mice with high penetrance. Targeted drug screening revealed unexpected selective vulnerabilities. Moreover, H3.3K27M tumors with PIK3CA, NF1 and FGFR1 mutations were more invasive and harbored distinct additional phenotypes, such as exophytic spread, cranial nerve invasion and spinal dissemination. Collectively, these models reveal that different partner alterations produce distinct effects on pHGG cellular composition, latency, invasiveness, and treatment sensitivity. Citation Format: Michael McNicholas, Antonella De Cola, Zahedeh Bashardanesh, Amelia Foss, Cameron Lloyd, Steven Hebert, Damien Faury, Augusto Faria Andrade, Nada Jabado, Claudia Kleinman, Manav Pathania. A compendium of syngeneic, transplantable pediatric high-grade glioma models reveals subtype-specific therapeutic vulnerabilities [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr B035.
Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma
Authors: Li Peng, Yanyi Jiang, Hengxing Chen, Yongqiang Wang, Qiusheng Lan, Shuiqin Chen, Zhanwang Huang, Jingyuan Zhang, Duanqing Tian, Yuntan Qiu, Diankui Cai, Jiangyun Peng, Daning Lu, Xiaoqing Yuan, Xianzhu Yang, Dong Yin
Journal: Acta Pharmaceutica Sinica B (2024)

Transcriptional dysregulation of genes is a hallmark of tumors and can serve as targets for cancer drug development. However, it is extremely challenging to develop small-molecule inhibitors to target abnormally expressed transcription factors (TFs) except for the nuclear receptor family of TFs. Little is known about the interaction between TFs and transcription cofactors in gastroesophageal adenocarcinoma (GEA) or the therapeutic effects of targeting TF and transcription cofactor complexes. In this study, we found that ETS homologous factor (EHF) expression is promoted by a core transcriptional regulatory circuitry (CRC), specifically ELF3-KLF5-GATA6, and interference with its expression suppressed the malignant biological behavior of GEA cells. Importantly, we identified Ajuba LIM protein (AJUBA) as a new coactivator of EHF that cooperatively orchestrates transcriptional network activity in GEA. Furthermore, we identified KRAS signaling as a common pathway downstream of EHF and AJUBA. Applicably, dual targeting of EHF and AJUBA by lipid nanoparticles cooperatively attenuated the malignant biological behaviors of GEA