tbuckley/cabot-search huggingface dataset:
Sync fast and solve things—best practices for responsible digital health
Authors: Constantin Landers, Alessandro Blasimme, Effy Vayena
Journal: npj Digital Medicine (2024)

Abstract Digital health innovation is expected to transform healthcare, but it also generates ethical and societal concerns, such as privacy risks, and biases that can compound existing health inequalities. While such concerns are widely recognized, existing regulatory principles, oversight methods and ethical frameworks seem out of sync with digital health innovation. New governance and innovation best practices are thus needed to bring such principles to bear with the reality of business, innovation, and regulation. To grant practical insight into best practices for responsible digital health innovation, we conducted a qualitative study based on an interactive engagement methodology. We engaged key stakeholders ( n = 46) operating at the translational frontier of digital health. This approach allowed us to identify three clusters of governance and innovation best practices in digital health innovation: i) inclusive co-creation, ii) responsive regulation, and iii) value-driven innovation. Our study shows that realizing responsible digital health requires diverse stakeholders’ commitment to adapt innovation and regulation practices, embracing co-creation as the default modus operandi for digital health development. We describe these collaborative practices and show how they can ensure that innovation is neither slowed by overregulation, nor leads to unethical outcomes.
Comment on “Glioblastoma patients’ survival and its relevant risk factors during the pre- and post-COVID-19 pandemic: Real-world cohort study in the USA and China”
Authors: Chaofan Fan, Peng Luo, Tong Jiang, Rui Li, Xin Chen
Journal: International Journal of Surgery (2024)

aDepartment of Pulmonary and Critical Care Medicine, Zhujiang Hospital of Southern Medical University, 253 Industrial Avenue, Guangzhou, Guangdong 510282, China bDepartment of Oncology, Zhujiang Hospital of Southern Medical University, 253 Industrial Avenue, Guangzhou, Guangdong 510282, China Running title: The COVID-19 pandemic influences cancer survival. Chaofan Fan, Peng Luo Contributed equally to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital of Southern Medical University, 253 Industrial Avenue, Guangzhou, Guangdong 510282, China. E-mail address: [email protected] (X. Chen). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Identification of <i>TP53</i> germline variants in pediatric patients undergoing tumor testing: strategy and prevalence
Authors: Minjie Luo, Derek Wong, Kristin Zelley, Jinhua Wu, Jeffery Schubert, Elizabeth H Denenberg, Elizabeth A Fanning, Jiani Chen, Daniel Gallo, Netta Golenberg, Maha Patel, Laura K Conlin, Kara N Maxwell, Gerald B Wertheim, Lea F Surrey, Yiming Zhong, Garrett M Brodeur, Suzanne P MacFarland, Marilyn M Li
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background TP53 alterations are common in certain pediatric cancers, making identification of putative germline variants through tumor genomic profiling crucial for disease management. Methods We analyzed TP53 alterations in 3123 tumors from 2788 pediatric patients sequenced using tumor-only or tumor-normal paired panels. Germline confirmatory testing was performed when indicated. Somatic and germline variants were classified based on published guidelines. Results In 248 tumors from 222 patients, 284 tier 1/2 TP53 sequence and small copy number variants were detected. Following germline classification, 86.6% of 142 unique variants were pathogenic or likely pathogenic. Confirmatory testing on 118 patients revealed germline TP53 variants in 28 of them (23 pathogenic or likely pathogenic and 5 of uncertain significance), suggesting a minimum Li-Fraumeni syndrome incidence of 0.8% (23/2788) in this cohort, 10.4% (23/222) in patients with TP53 variant–carrying tumors, and 19.5% (23/118) with available normal samples. About 25% (7/28) of patients with germline TP53 variants did not meet Li-Fraumeni syndrome diagnostic or testing criteria, while 20.9% (28/134) with confirmed or inferred somatic origins did. TP53 biallelic inactivation occurred in 75% of germline carrier tumors and was also prevalent in other groups, causing an elevated tumor-observed variant allelic fraction. Somatic evidence, however, including low variant allele fraction correctly identified only 27.8% (25/90) of patients with confirmed somatic TP53 variants. Conclusion The high incidence and variable phenotype of Li-Fraumeni syndrome in this cohort highlights the importance of assessing germline status of TP53 variants identified in all pediatric tumors. Without clear somatic evidence, distinguishing somatic from germline origins is challenging. Classifying germline and somatic variants should follow appropriate guidelines.
Cancer control co-benefits of the climate-related provisions in the American Inflation Reduction Act
Authors: Kilan C Ashad-Bishop, K Robin Yabroff, Leticia Nogueira
Journal: JNCI Journal of the National Cancer Institute (2024)

The American Inflation Reduction Act (IRA) of 2022 contains climate-related provisions that may have noteworthy implications for cancer control and prevention. This commentary assesses the potential co-benefits of the IRA for cancer control efforts, specifically policies and programs to reduce carcinogen exposure via air quality monitoring and air pollution reduction. Allocations through the IRA for air quality improvement, paired with its environmental justice provisions, hold promise for advancing cancer prevention by targeting resources to communities most susceptible to environmental hazards. Moreover, climate resilience measures dictated by the IRA are crucial for oncology professionals grappling with the dual challenges of climate change and cancer care. Climate-driven extreme weather events can exacerbate carcinogen exposure and disrupt access to cancer care, underscoring the need for resilient health-care infrastructure. The IRA's provisions for clean energy incentives and infrastructure upgrades offer oncology care institutions opportunities to mitigate emissions and bolster resilience against climate-related disruptions, ultimately improving cancer outcomes. Climate-related initiatives funded by the IRA present a unique and timely avenue to advance equitable cancer control efforts. This commentary underscores the critical intersection between climate resilience policy and oncology care, highlighting the potential to promote a healthier and more resilient future for all.
Establishing cell suitability for high-level production of licorice triterpenoids in yeast
Authors: Wentao Sun, Shengtong Wan, Chuyan Liu, Ruwen Wang, Haocheng Zhang, Lei Qin, Runming Wang, Bo Lv, Chun Li
Journal: Acta Pharmaceutica Sinica B (2024)

Yeast has been an indispensable host for synthesizing complex plant-derived natural compounds, yet the yields remained largely constrained. This limitation mainly arises from overlooking the importance of cell and pathway suitability during the optimization of enzymes and pathways. Herein, beyond conventional enzyme engineering, we dissected metabolic suitability with a framework for simultaneously augmenting cofactors and carbon flux to enhance the biosynthesis of heterogenous triterpenoids. We further developed phospholipid microenvironment engineering strategies, dramatically improving yeast's suitability for the high performance of endoplasmic reticulum (ER)-localized, rate-limiting plant P450s. Combining metabolic and microenvironment suitability by manipulating only three genes,
Quality-of-life outcomes in metastatic spinal cord compression: findings from the SCORAD trial
Authors: Peter J Hoskin, Krystyna Reczko, Memuna Rashid, Allan Hackshaw, Andre Lopes, K Hopkins, V Misra, T Holt, R McMenemin, F McKinna, M Krishnaswamy, A Bates, N O’Rourke, J Lester, T Sevitt, D Roos, G Brown, S Shibu Thomas, S Forsyth
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Purpose This article reports detailed quality-of-life data including preferred and actual place of care from SCORAD, the only large prospective randomized trial in metastatic spinal cord compression (MSCC). Methods SCORAD compared 2 doses of radiotherapy in patients with MSCC: 8 Gy single fraction and 20 Gy in 5 fractions. In total, 686 patients were randomized, of whom 590 had Health-Related Quality of Life (HRQoL) data collected at baseline and at least 1 later time point. HRQoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 supplemented with the QLU-C10D and data on place of care at weeks 1, 4, 8, and 12 postrandomization. Quality-of-Life Adjusted Survival was computed by multiplying Kaplan-Meier survival probabilities with the UK utility weights obtained from the QLU-C10D. Results Patients with a baseline physical functioning score of above 50 demonstrated a 28% reduction in the risk of death (hazard ratio [HR] = 0.72, 99% confidence interval [CI] = 0.54 to 0.95; P = .003). An increased risk of death was associated with fatigue (HR = 1.35, 99% CI = 1.03 to 1.76; P = .0040), dyspnea (HR = 1.61, 99% CI = 1.24 to 2.08; P &amp;lt; .001), and appetite loss (HR = 1.25, 99% CI = 0.99 to 1.59; P = .014). The preferred place of care for the majority was at home or with relatives (61%-74% across the 12 weeks) but achieved by only 53% at 8 weeks. Conclusions Prolonged survival in patients with MSCC was associated with better HRQoL. More than 60% of patients preferred to be cared for at home or with relatives, but only half were able to achieve this. There was no difference in HRQoL between the multifraction and single-fraction groups. Trial registration ISRCTN97555949 and ISRCTN97108008.
Using Computer-aided Optical Diagnosis and Expert Review to Evaluate Colorectal Polyps Diagnosed as Normal Mucosa in Pathology
Authors: Roupen Djinbachian, Mohammed El Mehdi El Yamani, Douglas K. Rex, Heiko Pohl, Mahsa Taghiakbari, Daniel von Renteln
Journal: Clinical Gastroenterology and Hepatology (2024)

Pathological assessment of colorectal polyps is considered the current reference standard for histologic diagnosis. About 10% of polyps sent to the pathology lab are returned with the diagnosis of mucosal folds, mucosal prolapse, or normal mucosa.
Simulation-based exercises to improve the performance of cosmetic consultations
Authors: Areeba Ahmed, Sarah Wilson, Rachel L. Kyllo, Eric Koza, Victoria Shi, Misha Haq, Melissa Ma, Emily Poon, Brandon Worley, Vishnu Harikumar, Ross Pearlman, Daniel I. Schlessinger, Brian A. Cahn, Murad Alam
Journal: Journal of the American Academy of Dermatology (2024)
Intermittent glucocorticoid treatment improves muscle metabolism via the PGC1α/Lipin1 axis in an aging-related sarcopenia model
Authors: Ashok D. Prabakaran, Kevin McFarland, Karen Miz, Hima Bindu Durumutla, Kevin Piczer, Fadoua El Abdellaoui Soussi, Hannah Latimer, Cole Werbrich, Hyun-Jy Chung, N. Scott Blair, Douglas P. Millay, Andrew J. Morris, Brendan Prideaux, Brian N. Finck, Mattia Quattrocelli
Journal: Journal of Clinical Investigation (2024)

Sarcopenia burdens the elderly population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are missing. The glucocorticoid prednisone remodels muscle metabolism based on frequency of intake, but its mechanisms in sarcopenia are unknown. We found that once-weekly intermittent prednisone rescued muscle quality in aged 24-month-old mice to levels comparable to young 4-month-old mice. We discovered an age- and sex-independent glucocorticoid receptor transactivation program in muscle encompassing PGC1α and its co-factor Lipin1. Treatment coordinately improved mitochondrial abundance through isoform 1 and muscle mass through isoform 4 of the myocyte-specific PGC1α, which was required for the treatment-driven increase in carbon shuttling from glucose to amino acid biogenesis. We also probed the myocyte-specific Lipin1 as non-redundant factor coaxing PGC1α upregulation to the stimulation of both oxidative and anabolic effects. Our study unveils an aging-resistant druggable program in myocytes to coordinately rescue energy and mass in sarcopenia.
Radioligand therapies in meningioma – evidence and future directions
Authors: Maximilian J Mair, Emeline Tabouret, Derek R Johnson, Erik P Sulman, Patrick Y Wen, Matthias Preusser, Nathalie L Albert
Journal: Neuro-Oncology (2024)

Abstract Meningiomas are the most common intracranial neoplasms in adults. While most meningiomas are cured by resection, further treatment by radiotherapy may be needed, particularly in WHO grades 2 and 3 tumors which have an increased risk of recurrence, even after conventional therapies. Still, there is an urgent need for novel therapeutic strategies after the exhaustion of local treatment approaches. Radionuclide therapies combine the specificity of tumor-specific antibodies or ligands with the cytotoxic activity of radioactive emitters. Alongside this, integrated molecular imaging allows for a noninvasive assessment of predictive biomarkers as treatment targets. Whereas the concept of “theranostics” has initially evolved in extracranial tumors such as thyroid diseases, neuroendocrine tumors, and prostate cancer, data from retrospective case series and early phase trials underscore the potential of this strategy in meningioma. This review aims to explore the available evidence of radionuclide treatments and ongoing clinical trial initiatives in meningioma. Moreover, we discuss optimal clinical trial design and future perspectives in the field, including compound- and host-specific determinants of the efficacy of “theranostic” treatment approaches.
BTK drives neutrophil activation for sterilizing antifungal immunity
Authors: Jigar V. Desai, Marissa A. Zarakas, Andrew L. Wishart, Mark Roschewski, Mariano A. Aufiero, Agnes Donkò, Gustaf Wigerblad, Neta Shlezinger, Markus Plate, Matthew R. James, Jean K. Lim, Gulbu Uzel, Jenna R.E. Bergerson, Ivan Fuss, Robert A. Cramer, Luis M. Franco, Emily S. Clark, Wasif N. Khan, Daisuke Yamanaka, Georgios Chamilos, Jamel El-Benna, Mariana J. Kaplan, Louis M. Staudt, Thomas L. Leto, Steven M. Holland, Wyndham H. Wilson, Tobias M. Hohl, Michail S. Lionakis
Journal: Journal of Clinical Investigation (2024)

We describe a previously-unappreciated role for Bruton's tyrosine kinase (BTK) in fungal immune surveillance against aspergillosis, an unforeseen complication of BTK inhibitors (BTKi) used for treating B-cell lymphoid malignancies. We studied BTK-dependent fungal responses in neutrophils from diverse populations, including healthy donors, BTKi-treated patients, and X-linked agammaglobulinemia patients. Upon fungal exposure, BTK was activated in human neutrophils in a TLR2-, Dectin-1-, and FcγR-dependent manner, triggering the oxidative burst. BTK inhibition selectively impeded neutrophil-mediated damage to Aspergillus hyphae, primary granule release, and the fungus-induced oxidative burst by abrogating NADPH oxidase subunit p40phox and GTPase RAC2 activation. Moreover, neutrophil-specific Btk deletion in mice enhanced aspergillosis susceptibility by impairing neutrophil function, not recruitment or lifespan. Conversely, GM-CSF partially mitigated these deficits by enhancing p47phox activation. Our findings underline the crucial role of BTK signaling in neutrophils for antifungal immunity and provide a rationale for GM-CSF use to offset these deficits in susceptible patients.
The time-lagged impact of microaggressions at work on the emotional exhaustion of transgender and gender diverse employees
Authors: Daniel Cancela, Sarah E. Stutterheim, Sjir Uitdewilligen, Ute R. Hülsheger
Journal: International Journal of Transgender Health (2024)

Background Despite the widespread adoption of workplace protections for transgender and gender diverse (TGD) individuals, past research has suggested that microaggressions still occur. Previous literature indicates that microaggressions have a deleterious and cumulative impact on mental health. However, little is known about how microaggressions affect TGD employees over time.
A systematic comparison of deep learning methods for Gleason grading and scoring
Authors: Juan P. Dominguez-Morales, Lourdes Duran-Lopez, Niccolò Marini, Saturnino Vicente-Diaz, Alejandro Linares-Barranco, Manfredo Atzori, Henning Müller
Journal: Medical Image Analysis (2024)

Prostate cancer is the second most frequent cancer in men worldwide after lung cancer. Its diagnosis is based on the identification of the Gleason score that evaluates the abnormality of cells in glands through the analysis of the different Gleason patterns within tissue samples. The recent advancements in computational pathology, a domain aiming at developing algorithms to automatically analyze digitized histopathology images, lead to a large variety and availability of datasets and algorithms for Gleason grading and scoring. However, there is no clear consensus on which methods are best suited for each problem in relation to the characteristics of data and labels. This paper provides a systematic comparison on nine datasets with state-of-the-art training approaches for deep neural networks (including fully-supervised learning, weakly-supervised learning, semi-supervised learning, Additive-MIL, Attention-Based MIL, Dual-Stream MIL, TransMIL and CLAM) applied to Gleason grading and scoring tasks. The nine datasets are collected from pathology institutes and openly accessible repositories. The results show that the best methods for Gleason grading and Gleason scoring tasks are fully supervised learning and CLAM, respectively, guiding researchers to the best practice to adopt depending on the task to solve and the labels that are available.
The interferon story continues: EORTC CLTG study explores pegylated interferon α-2a’s role in treating mycosis fungoides/Sézary syndrome
Authors: Rudolf Stadler
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript The Interferon story continues: EORTC CLTG Study Explores Pegylated Interferon Alpha-2α's Role in Treating Mycosis Fungoides/Sézary Syndrome Get access Rudolf Stadler Rudolf Stadler University Department for Dermatology, Venerology, Allergology and Phlebology, Skin Cancer Center, Johannes Wesling Medical Center, UKRUB, University of Bochum, Minden, Germany Email:rudolf.stadler@ruhr-uni-bochum.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae188, https://doi.org/10.1093/bjd/ljae188 Published: 04 May 2024 Article history Received: 20 April 2024 Revision received: 22 April 2024 Accepted: 02 May 2024 Published: 04 May 2024
Deceptive pigment changes in neoadjuvant sonidegib therapy for basal cell carcinoma
Authors: Shenxi Zhang, Menglong Ran
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript Deceptive Pigment Changes in Neoadjuvant Sonidegib Therapy for Basal Cell Carcinoma Get access Shenxi Zhang, Shenxi Zhang Department of Dermatology and Venereology, Peking University First Hospital, Beijing, ChinaKey Laboratory of Molecular Diagnosis on Dermatoses; National Clinical Research Center for Skin and Immune Diseases; NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China https://orcid.org/0000-0001-9223-416X Search for other works by this author on: Oxford Academic Google Scholar Menglong Ran Menglong Ran Department of Dermatology and Venereology, Peking University First Hospital, Beijing, ChinaKey Laboratory of Molecular Diagnosis on Dermatoses; National Clinical Research Center for Skin and Immune Diseases; NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China Corresponding author: Menglong Ran, MD. Email:rss-47@163.com https://orcid.org/0000-0002-5962-207X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae187, https://doi.org/10.1093/bjd/ljae187 Published: 04 May 2024 Article history Received: 10 January 2024 Revision received: 25 April 2024 Accepted: 02 May 2024 Published: 04 May 2024
Preparation of NIR‐II Polymer Nanoprobe Through Twisted Intramolecular Charge Transfer and Förster Resonance Energy Transfer of NIR‐I Dye
Authors: Bin Xia, Feng Ren, Xiaopeng Ma, Zheng‐Chuan Yang, Zhi‐Lin Jiang, Wei‐Wei Fang, Ning‐Wei Wang, Jin‐Long Hu, Wei‐Duo Zhu, Tao He, Qing Li, Bao‐Qiang Cao, Zhen Li
Journal: Advanced Healthcare Materials (2024)

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.