tbuckley/cabot-search huggingface dataset:
Niche-DE: niche-differential gene expression analysis in spatial transcriptomics data identifies context-dependent cell-cell interactions
Authors: Kaishu Mason, Anuja Sathe, Paul R. Hess, Jiazhen Rong, Chi-Yun Wu, Emma Furth, Katalin Susztak, Jonathan Levinsohn, Hanlee P. Ji, Nancy Zhang
Journal: Genome biology (2024)

Abstract Existing methods for analysis of spatial transcriptomic data focus on delineating the global gene expression variations of cell types across the tissue, rather than local gene expression changes driven by cell-cell interactions. We propose a new statistical procedure called niche-differential expression (niche-DE) analysis that identifies cell-type-specific niche-associated genes, which are differentially expressed within a specific cell type in the context of specific spatial niches. We further develop niche-LR, a method to reveal ligand-receptor signaling mechanisms that underlie niche-differential gene expression patterns. Niche-DE and niche-LR are applicable to low-resolution spot-based spatial transcriptomics data and data that is single-cell or subcellular in resolution.
Silent crisis of venous care in UK
Authors: Bruce Campbell, Daniel Carradice
Journal: BMJ (2024)

High quality evidence clearly supports the treatment of common venous diseases.Treatment of symptomatic varicose veins improves quality of life and is highly cost effective, 1-4 while early treatment of venous leg ulcers speeds healing, reduces recurrence, and potentially reduces costs. [5]6][7][8] Despite this strong evidence, and National Institute for Health and Care Excellence (NICE) guidance recommending referral of people with symptomatic primary or recurrent varicose veins, 2 access to treatment for symptomatic varicose veins is restricted in much of the UK and people who develop leg ulcers experience delay in getting the treatment they need for underlying venous disease. 9 10Preventing and treating leg ulceration is perhaps the most pressing issue.The importance of early referral and specialist treatment was highlighted in the 2019 report of the All Party Parliamentary Committee on Vascular and Venous Disease, Venous Leg Ulcers: a Silent Crisis. 10Community treatment of venous leg ulcers costs the NHS £1bn-£2bn annually, much of which could be saved by correcting the causative venous hypertension in underlying varicose veins. 8 Recognising venous skin damage-eczema, lipodermatosclerosis, pigmentation-and treating the veins before ulcers develop is recognised as particularly important, 11 and guidance from the Venous Forum of the Royal Society of Medicine recommends that anyone who develops a leg ulcer should be seen by a vascular specialist within two weeks. 12 Unfortunately, no meaningful progress has been made on meeting the parliamentary committee's 2019 recommendations, or those in its 2023 report,
ICON 2020—International Scientific Tendinopathy Symposium Consensus: the development of a core outcome set for gluteal tendinopathy
Authors: Angela M Fearon, Alison Grimaldi, Rebecca Mellor, Anthony Michael Nasser, Jane Fitzpatrick, Andreas Ladurner, Bill Vicenzino
Journal: British Journal of Sports Medicine (2024)

Gluteal tendinopathy (GT) is common and can be debilitating and challenging to manage. A lack of condition specific and appropriate outcome measures compromise evidence synthesis for treatment and limits clinical guideline development. Our objective was to develop a core outcome measurement set for GT (COS-GT). Participants were patients with GT and expert health professionals (HPs). A scoping review identified measures used in GT research, which were mapped to the nine International Scientific Tendinopathy Symposium Consensus core domains, and included in two surveys of HPs. The first survey identified the feasible and true measures for each domain. The second survey refined the list which a patient focus group then considered. Meeting online, HPs reached consensus (agreement ≥70%) on the most appropriate COS-GT measures. 34 HPs and seven patients were recruited. 57 measures were mapped to the nine core domains. Six measures did not proceed past survey one. Of those that progressed, none had adequate clinimetric properties for a COS-GT. Thus, participants decided on interim measures: the global rating of change, pain at night, time to pain onset with single limb stance, pain with stair walking, pain self-efficacy and hip abduction strength. HP participants additionally recommended that pain over the last week, the European Quality of Life-5 dimensions-5 levels and the Victorian Institute of Sport Assessment-Gluteal be considered in clinical trials, as they currently provide best easures of the relevant tendinopathy domains. In conclusion this interim COS-GT should guide outcome measure selection in clinical practice and future research trials in patients with GT.
Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices
Authors: Noehyun Myung, Hyun-Wook Kang
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer (TNBC), a highly aggressive disease with a poor prognosis. This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals, allowing for promising clinical outcomes with intensive treatment. However, the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance, limiting therapeutic efficacy and clinical benefit. Here, we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with time-programmed pulsatile release profiles. The implantable device can control the time between drug releases based on its internal microstructure design, which can be used to control dose density. The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar. Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo. Under the same dose density conditions, device-based chemotherapy shows a higher anti-cancer effect and less toxic response than intratumoral injection. We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose, number of releases, and treatment duration of the dose-dense AC (doxorubicin and cyclophosphamide) regimen preferred for TNBC treatment. Dose density modulation inhibits tumor growth, metastasis, and the expression of drug resistance-related proteins, including p-glycoprotein and breast cancer resistance protein. To the best of our knowledge, local dose-dense chemotherapy has not been reported, and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.
When I use a word . . . Lexicographic anniversaries in 2024
Authors: Jeffrey K Aronson
Journal: BMJ (2024)

Like people, words have birthdays. My definition of the birthday of a word is the year in which it first appeared in a written text, as, for example, documented in the <i>Oxford English Dictionary</i> (<i>OED</i>). Even though many words have had a conversational life preceding their written one, I count that as the fetal stage in their development. Their appearance in the world is marked by their first appearance in print. In some cases the documented birthday can be antedated by finding earlier examples of the use of the word in print; in my experience, this happens to about 10% of biomedical words. Counting anniversaries as having occurred in multiples of 50 years, I have searched for biomedical words whose birthdays fell in years ending in '24 and '74 and have found 144 of them. Among these, my favourites are "impostumation," an obsolete word for an abscess, dating from 1524, as used by William Harvey in prescriptions he wrote in 1653 and 1655 for John Aubrey; "cybrid," a word still used, although unfamiliar to many, which dates from 1974, a hybrid term for a hybrid type of cell; and "quinine," which the dictionary attests as dating from 1824, earlier examples of which can be found. There are many interesting stories to be discovered by investigating the birthdays of words.
Feasibility and oncologic efficacy of robotic vs. open liver resection for large and huge hepatocellular carcinoma
Authors: Lorenzo Bernardi, Emanuele Balzano, Davide Ghinolfi, Alessandra Cristaudi
Journal: International Journal of Surgery (2024)

Bernardi, Lorenzo Dr; Balzano, Emanuele Dr; Ghinolfi, Davide Dr; Cristaudi, Alessandra Dr Author Information
Abstract B014: KDM4B mutations in human cancers
Authors: Wesley A. Bush, Ruben C. Petreaca
Journal: Cancer Research (2024)

Abstract Homology-dependent-repair (HDR) is an essential process for the error-free correction of double-strand-breaks (DSBs). The histone demethylase KDM4B plays a role in the HDR repair process, wherein its H3K9 demethylase activity aids recruitment of repair factors such as the ATM checkpoint activator and KAT5 histone acetyltransferase and remodeler to the break site. Inhibition of KDM4B has been shown to disrupt the recruitment of ATM, and KAT5, affecting other downstream HDR factors and leading to widespread unrepaired DNA damage. Both over- and under-expression of KDM4B have implications for cancer severity, and changes in KDM4B expression have been shown to affect the expression of other oncogenes outside of the HDR pathway. We performed a pan-cancer analysis of the effects of KDM4B alterations in human cancers using data from the Catalogue of Somatic Mutations in Cancers (COSMIC). We find that KDM4B mutations occur in nearly every cancer. Further, there is a tendency of co-occurring mutations between KDM4B and several HDR genes the most significant being BRCA2. Machine learning tools did not predict any of the observed KDM4B mutations to be drivers. Our data suggests that although KDM4B does not display a driver phenotype it contributes to the destabilization of DNA damage repair machinery that causes cellular transformation and immortalization. Citation Format: Wesley A. Bush, Ruben C. Petreaca. KDM4B mutations in human cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B014.
Abstract B016: Developing diagnostic tools via mutational spectra analysis and multiomic plasma profiling from liquid biopsies to identify potential signatures in cancer in Trinidad and Tobago
Authors: Nicole Ramlachan, Samuel M. West
Journal: Cancer Research (2024)

Abstract Cancer, especially lung cancer is a leading cause of nosocomial deaths worldwide. Non-small cell lung cancer (NSCLC) has a five-year survival rate of only 24%. Early diagnoses markedly improves survival with personalized cancer therapies using non-invasive techniques for asymptomatic detection of mutational spectrum-related by genotyping NSCLC patients, even prior to symptoms. Analysis of conformational change in proteins due to mutations in oncogenes allow for mutation-specific treatment with specialized cancer drugs. In addition, tumor mutational burden (TMB) is a promising predictive biomarker for cancer immunotherapy as high TMB patients respond better to immune checkpoint inhibitors cancer drugs. Treatment planning for non-small cell lung cancer generally requires testing for EGFR, ALK, ROS1, BRAF, MET, RET and KRAS gene alterations or whole genome analysis to assess TMB. The Caribbean region remains disadvantaged by the lack of available genetic testing mainly due to accessibility. We propose the genotyping of 30 stage III-IV NSCLC patients via next-generation sequencing (NGS) to improve personalized therapies. Through the analysis of tumor-specific alterations amongst a complete mutation spectrum analysis, including single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs), and methylation alterations, we would generate data to be used as an accurate form of cancer genotyping for diagnostic purposes. We intend to include these genes as biomarkers in a mutational spectrum analysis, to be collated into a predictive DNA assay to be used for the first time as a diagnostic/prognostic tool in a medically underserved community. We intend to also identify TMB-high patients without cost-prohibitive whole genome sequencing by focusing on DNA damage repair (DDR) genes. There is an increasing utilization of agnostic testing which involves the analysis of all potentially actionable genes across all tumor and cancer types. The invention of genomic-tailored specialized cancer treatments has resulted in a spectacular improvement in disease outcomes for a significant portion of cancer patients, which we hope to offer to improve clinical outcomes and prognosis in the racially diverse population of Trinidad and Tobago. Citation Format: Nicole Ramlachan, Samuel M. West. Developing diagnostic tools via mutational spectra analysis and multiomic plasma profiling from liquid biopsies to identify potential signatures in cancer in Trinidad and Tobago [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B016.
Abstract A033: The ING5 epigenetic reader regulates a subset of DNA repair genes to maintain genomic integrity
Authors: Arthur E Dantas, Buthaina Al-Shueili, Mahbod Djamshidi, Karl Riabowol
Journal: Cancer Research (2024)

Abstract The ING family of epigenetic histone code readers (ING1-5) recognize the H3K4Me3 epigenetic mark to target histone acetyltransferase (HAT) or histone deacetylase (HDAC) complexes to regulate local acetylation levels and affect transcription. We and others have shown that ING5 promotes stem cell character in normal and in cancer stem cells and that loss of ING5 promotes stem cell differentiation. Examination of an ING5 knockout (KO) mouse model showed increased levels of DNA damage in different tissues, and particularly in the male germ line. ING5 mouse embryo fibroblasts (MEFs) also show a &amp;gt;2-fold increase in cells containing gH2AX foci in the absence of exogenous DNA damaging agents. Examining the transcriptomes of ING5 KO and wild-type littermate MEFs indicates that several genes encoding key DNA repair proteins such as those acting in homologous recombination (BRCA1 and BRCA2) and base excision repair (PARP1) are repressed several-fold and ING5 KO MEFs show increased sensitivity to the PARP inhibitor olaparib. Given that ING5 functions to help maintain stem cell character in normal and in cancer stem cells, we propose that ING5 serves a role in maintaining a high level of DNA repair capability in stem cell populations to preserve genomic integrity. Citation Format: Arthur E Dantas, Buthaina Al-Shueili, Mahbod Djamshidi, Karl Riabowol. The ING5 epigenetic reader regulates a subset of DNA repair genes to maintain genomic integrity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A033.
Microinstrumentation for Brain Organoids
Authors: Devan Patel, Saniya Shetty, Chris Acha, Itzy E. Morales Pantoja, Alice Zhao, Derosh George, David H. Gracias
Journal: Advanced Healthcare Materials (2024)

Brain organoids are three-dimensional aggregates of self-organized differentiated stem cells that mimic the structure and function of human brain regions. Organoids bridge the gaps between conventional drug screening models such as planar mammalian cell culture, animal studies, and clinical trials. They can revolutionize the fields of developmental biology, neuroscience, toxicology, and computer engineering. Conventional microinstrumentation for conventional cellular engineering, such as planar microfluidic chips; microelectrode arrays (MEAs); and optical, magnetic, and acoustic techniques, has limitations when applied to three-dimensional (3D) organoids, primarily due to their limits with inherently two-dimensional geometry and interfacing. Hence, there is an urgent need to develop new instrumentation compatible with live cell culture techniques and with scalable 3D formats relevant to organoids. This review discusses conventional planar approaches and emerging 3D microinstrumentation necessary for advanced organoid-machine interfaces. Specifically, this article surveys recently developed microinstrumentation, including 3D printed and curved microfluidics, 3D and fast-scan optical techniques, buckling and self-folding MEAs, 3D interfaces for electrochemical measurements, and 3D spatially controllable magnetic and acoustic technologies relevant to two-way information transfer with brain organoids. This article highlights key challenges that must be addressed for robust organoid culture and reliable 3D spatiotemporal information transfer.
Implementation of cloud computing in the German healthcare system
Authors: M. Putzier, T. Khakzad, M. Dreischarf, S. Thun, F. Trautwein, N. Taheri
Journal: npj Digital Medicine (2024)

Abstract With the advent of artificial intelligence and Big Data - projects, the necessity for a transition from analog medicine to modern-day solutions such as cloud computing becomes unavoidable. Even though this need is now common knowledge, the process is not always easy to start. Legislative changes, for example at the level of the European Union, are helping the respective healthcare systems to take the necessary steps. This article provides an overview of how a German university hospital is dealing with European data protection laws on the integration of cloud computing into everyday clinical practice. By describing our model approach, we aim to identify opportunities and possible pitfalls to sustainably influence digitization in Germany.
Digital remote monitoring for screening and early detection of urinary tract infections
Authors: Alexander Capstick, Francesca Palermo, Kimberley Zakka, Nan Fletcher-Lloyd, Chloe Walsh, Tianyu Cui, Samaneh Kouchaki, Raphaella Jackson, Martin Tran, Michael Crone, Kirsten Jensen, Paul Freemont, Ravi Vaidyanathan, Magdalena Kolanko, Jessica True, Sarah Daniels, David Wingfield, Ramin Nilforooshan, Payam Barnaghi
Journal: npj Digital Medicine (2024)

Abstract Urinary Tract Infections (UTIs) are one of the most prevalent bacterial infections in older adults and a significant contributor to unplanned hospital admissions in People Living with Dementia (PLWD), with early detection being crucial due to the predicament of reporting symptoms and limited help-seeking behaviour. The most common diagnostic tool is urine sample analysis, which can be time-consuming and is only employed where UTI clinical suspicion exists. In this method development and proof-of-concept study, participants living with dementia were monitored via low-cost devices in the home that passively measure activity, sleep, and nocturnal physiology. Using 27828 person-days of remote monitoring data (from 117 participants), we engineered features representing symptoms used for diagnosing a UTI. We then evaluate explainable machine learning techniques in passively calculating UTI risk and perform stratification on scores to support clinical translation and allow control over the balance between alert rate and sensitivity and specificity. The proposed UTI algorithm achieves a sensitivity of 65.3% (95% Confidence Interval (CI) = 64.3–66.2) and specificity of 70.9% (68.6–73.1) when predicting UTIs on unseen participants and after risk stratification, a sensitivity of 74.7% (67.9–81.5) and specificity of 87.9% (85.0–90.9). In addition, feature importance methods reveal that the largest contributions to the predictions were bathroom visit statistics, night-time respiratory rate, and the number of previous UTI events, aligning with the literature. Our machine learning method alerts clinicians of UTI risk in subjects, enabling earlier detection and enhanced screening when considering treatment.
Influence of age, socioeconomic status, and location on the infant gut resistome across populations
Authors: Dhrati V. Patangia, Ghjuvan Grimaud, Shaopu Wang, R. Paul Ross, Catherine Stanton
Journal: Gut Microbes (2024)

Antibiotic resistance is a growing global concern, with many ecological niches showing a high abundance of antibiotic resistance genes (ARGs), including the human gut. With increasing indications of ARGs in infants, this study aims to investigate the gut resistome profile during early life at a wider geographic level. To achieve this objective, we utilized stool samples data from 26 studies involving subjects aged up to 3 years from different geographical locations. The 32,277 Metagenome Assembled Genomes (MAGs) previously generated from shotgun sequencing reads from these studies were used for resistome analysis using RGI with the CARD database. This analysis showed that the distribution of ARGs across the countries in our study differed in alpha diversity and compositionally. In particular, the abundance of ARGs was found to vary by socioeconomic status and healthcare access and quality (HAQ) index. Surprisingly, countries having lower socioeconomic status and HAQ indices showed lower ARG abundance, which was contradictory to previous reports. Gram-negative genera, including Escherichia, Enterobacter, Citrobacter, and Klebsiella harbored a particularly rich set of ARGs, which included antibiotics that belong to the Reserve, Access or Watch category, such as glycopeptides, fluoroquinolones, sulfonamides, macrolides, and tetracyclines. We showed that ARG abundance exponentially decreased with time during the first 3 years of life. Many highly ARG-abundant species including Escherichia, Klebsiella, Citrobacter species that we observed are well-known pathobionts found in the infant gut in early life. High abundance of these species and a diverse range of ARGs in their genomes point toward the infant gut, acting as an ARG reservoir. This is a concern and further studies are needed to examine the causal effect and its consequences on long-term health.
Responding to Medical Errors — Implementing the Modern Ethical Paradigm
Authors: Thomas H Gallagher, Allen Kachalia
Journal: New England Journal of Medicine (2024)

Audio Interview Interview with Thomas Gallagher on historical and current ethical approaches to responding to harmful medical errors. 17m 25s Download AbstractUnder communication and resolution programs, health care providers aim to minimize suffering and promote learning when patient harm occurs. Doing so is especially challenging when harm was due to an error.