tbuckley/cabot-search huggingface dataset:
Linking microbial genes to plasma and stool metabolites uncovers host-microbial interactions underlying ulcerative colitis disease course
Authors: Melanie Schirmer, Martin Stražar, Julian Avila-Pacheco, Daniel F. Rojas-Tapias, Eric M. Brown, Emily Temple, Amy Deik, Kevin Bullock, Sarah Jeanfavre, Kerry Pierce, Shen Jin, Rachele Invernizzi, Marie-Madlen Pust, Zach Costliow, David R. Mack, Anne M. Griffiths, Thomas Walters, Brendan M. Boyle, Subra Kugathasan, Hera Vlamakis, Jeffrey Hyams, Lee Denson, Clary B. Clish, Ramnik J. Xavier
Journal: Cell Host & Microbe (2024)
2024: A year to reinterpret medicine’s maladies
Authors: Kamran Abbasi
Journal: BMJ (2024)

In Jumpha Lahiri's Pulitzer prize winning book The Interpreter of Maladies Mr Kapasi is a driver and tour guide who also works as a medical translator.Kapasi's duty in the doctor's clinic is to translate without passing judgment.His passenger describes Kapasi's translation job as "romantic," something that surprises him and would equally surprise most people working in today's healthcare environment of systemwide maladies.
Instability of the HLA-E peptidome of HIV presents a major barrier to therapeutic targeting
Authors: Zoë Wallace, Tiaan Heunis, Rachel L. Paterson, Richard J. Suckling, Tressan Grant, Marcin Dembek, Jose Donoso, Jacqui Brener, Joshua Long, Wilawan Bunjobpol, Dawn Gibbs-Howe, Daniel P. Kay, Darren B. Leneghan, Luis F. Godinho, Andrew Walker, Praveen K. Singh, Andrew Knox, Sarah Leonard, Lucy Dorrell
Journal: Molecular Therapy (2024)

Naturally occurring T cells that recognize microbial peptides via HLA-E, a nonpolymorphic HLA class Ib molecule, could provide the foundation for new universal immunotherapeutics. However, confidence in the biological relevance of putative ligands is crucial, given that the mechanisms by which pathogen-derived peptides can access the HLA-E presentation pathway are poorly understood. We systematically interrogated the HIV proteome using immunopeptidomic and bioinformatic approaches, coupled with biochemical and cellular assays. No HIV HLA-E peptides were identified by tandem mass spectrometry analysis of HIV-infected cells. In addition, all bioinformatically predicted HIV peptide ligands (>80) were characterized by poor complex stability. Furthermore, infected cell elimination assays using an affinity-enhanced T cell receptor bispecific targeted to a previously reported HIV Gag HLA-E epitope demonstrated inconsistent presentation of the peptide, despite normal HLA-E expression on HIV-infected cells. This work highlights the instability of the HIV HLA-E peptidome as a major challenge for drug development. Naturally occurring T cells that recognize microbial peptides via HLA-E, a nonpolymorphic HLA class Ib molecule, could provide the foundation for new universal immunotherapeutics. However, confidence in the biological relevance of putative ligands is crucial, given that the mechanisms by which pathogen-derived peptides can access the HLA-E presentation pathway are poorly understood. We systematically interrogated the HIV proteome using immunopeptidomic and bioinformatic approaches, coupled with biochemical and cellular assays. No HIV HLA-E peptides were identified by tandem mass spectrometry analysis of HIV-infected cells. In addition, all bioinformatically predicted HIV peptide ligands (>80) were characterized by poor complex stability. Furthermore, infected cell elimination assays using an affinity-enhanced T cell receptor bispecific targeted to a previously reported HIV Gag HLA-E epitope demonstrated inconsistent presentation of the peptide, despite normal HLA-E expression on HIV-infected cells. This work highlights the instability of the HIV HLA-E peptidome as a major challenge for drug development.
Visualization Materials Using Silicon‐Based Optical Nanodisks (ViSiON) for Enhanced NIR Imaging in Ophthalmology
Authors: Jisun Ki, Hyunji Lee, Tae Geol Lee, Sang‐Won Lee, Jung‐Sub Wi, Hee‐Kyung Na
Journal: Advanced Healthcare Materials (2024)

ViSiON (visualization materials composed of silicon-based optical nanodisks) is presented, which offers a unique optical combination of near-infrared (NIR) optical properties and biodegradability. Initially, numerical simulations are conducted to calculate the total extinction and scattering effects of ViSiON by the diameter-to-thickness ratio, predicting precise control over its scattering properties in the NIR region. A top-down patterning technique is employed to synthesize ViSiON with accurate diameter and thickness control. ViSiON with a 50 nm thickness exhibits scattering properties over 400 times higher than that of 30 nm, rendering it suitable as a contrast agent for optical coherence tomography (OCT), especially in ophthalmic applications. Furthermore, ViSiON possesses inherent biodegradability in media, with ≈95% degradation occurring after 48 h, and the degradation rate can be finely tuned based on the quantity of protein coating applied to the surface. Subsequently, the OCT imaging capability is validated even within vessels smaller than 300 µm, simulating retinal vasculature using a retinal phantom. Then, using an ex ovo chick embryo model, it is demonstrated that ViSiON enhances the strength of protein membranes by 6.17 times, thereby presenting the potential for ViSiON as an OCT imaging probe capable of diagnosing retinal diseases.
Safety and efficacy of dihydroartemisinin–piperaquine for intermittent preventive treatment of malaria in pregnant women with HIV from Gabon and Mozambique: a randomised, double-blind, placebo-controlled trial
Authors: Raquel González, Tacilta Nhampossa, Ghyslain Mombo-Ngoma, Johannes Mischlinger, Meral Esen, André-Marie Tchouatieu, Anete Mendes, Antía Figueroa-Romero, Rella Zoleko-Manego, Bertrand Lell, Heimo Lagler, Linda Stoeger, Lia Betty Dimessa, Myriam El Gaaloul, Sergi Sanz, Susana Méndez, Mireia Piqueras, Esperança Sevene, Michael Ramharter, Francisco Saúte, Clara Menendez, Frédérique Mbang Abba, Marc Bañuls, Saskia Dede Davi, Wilfrid Ndzebe Ndoumba, Maura Mazuze, Ulysse Pascale Minkobame Zaga Minko, Clara Pons-Duran, Arnau Vañó-Boira, Teodora Vaz
Journal: The Lancet Infectious Diseases (2024)
The importance of using WHO International Standards to harmonise SARS-CoV-2 serological assays
Authors: Heidi Hempel, Mark Page, Troy Kemp, Amanda Semper, Tim Brooks, Ligia A Pinto
Journal: The Lancet Microbe (2024)

The COVID-19 pandemic led to the rapid development of tests to diagnose SARS-CoV-2 infection and ascertain the prevalence of infection, along with the formulation of various treatments and vaccines. Globally, over 220 anti-SARS-CoV-2 serological assays have been developed for laboratory use, and many of these assays are currently used to assess immune responses against SARS-CoV-2. However, because these assays were independently developed by different manufacturers with different target antigens, immunoglobulin detection, technologies, and data reporting approaches, the results are not directly comparable, making it challenging to draw conclusions regarding immune responses at the population level. With deficiencies in assay validation, standardisation, and harmonisation, the inability to use and compare large datasets is becoming a major issue as serological data continue to increase. To help in addressing this issue, WHO established the first International Standard for the anti-SARS-CoV-2 immunoglobulin in late 2020. In this Personal View, we define the WHO International Standard for the anti-SARS-CoV-2 immunoglobulin, summarise the uses of primary versus secondary serology standards, recommend the use of such standards for data harmonisation, and list guidance and resources for using serology standards to improve data comparability.
Cladribine improves cutaneous manifestations, Dermatology Life Quality Index, and Mastocytosis Quality of Life of patients with mastocytosis
Authors: Hélène Bugaut, Hervé Maillard, Caroline Jacobzone, Naeda Haddad, François Le Pelletier, Frédéric Charlotte, Michel Arock, Patrice Dubreuil, Cristina Bulai Livideanu, Olivier Hermine, Stéphane Barete
Journal: Journal of the American Academy of Dermatology (2024)
A Two-color Single-molecule Sequencing Platform and Its Clinical Applications
Authors: Fang Chen, Bin Liu, Meirong Chen, Zefei Jiang, Zhiliang Zhou, Ping Wu, Meng Zhang, Huan Jin, Linsen Li, Liuyan Lu, Huan Shang, Lei Liu, Weiyue Chen, Jianfeng Xu, Ruitao Sun, Guangming Wang, Jiao Zheng, Jifang Qi, Bo Yang, Lidong Zeng, Yan Li, Hui Lv, Nannan Zhao, Wen Wang, Jinsen Cai, Yongfeng Liu, Weiwei Luo, Juan Zhang, Yanhua Zhang, Jicai Fan, Haitao Dan, Xuesen He, Wei Huang, Lei Sun, Qin Yan
Journal: Genomics Proteomics & Bioinformatics (2024)

DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years. In this study, we developed a single-molecule desktop sequencer, GenoCare 1600 (GenoCare), which utilizes amplification-free library preparation and two-color sequencing-by-synthesis chemistry, making it more user-friendly compared with previous single-molecule sequencing platforms for clinical use. Using the GenoCare platform, we sequenced an Escherichia coli standard sample and achieved a consensus accuracy exceeding 99.99%. We also evaluated the sequencing performance of this platform in microbial mixtures and coronavirus disease 2019 (COVID-19) samples from throat swabs. Our findings indicate that the GenoCare platform allows for microbial quantitation, sensitive identification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and accurate detection of virus mutations, as confirmed by Sanger sequencing, demonstrating its remarkable potential in clinical application.
Modified posterior colporrhaphy: a better technique to improve sexual function in women with vaginal laxity
Authors: Si-hong Shen, Jia-wei Chen, Meng-zhu Liu, Liao Peng, Yuan-zhuo Chen, Hong Shen, De-yi Luo
Journal: International Journal of Surgery (2024)

Shen, Si-hong MM; Chen, Jia-wei MM; Liu, Meng-zhu MM; Peng, Liao MD; Chen, Yuan-zhuo MD; Shen, Hong MD; Luo, De-yi MD, PhD Author Information
New horizons in polyp size estimation
Authors: Yuichi Mori
Journal: Endoscopy (2024)

While performing a colonoscopy for a 60-year-old gentleman on a cozy afternoon in November, you may find a relatively small adenoma in the sigmoid colon and remove it. If you estimate its size to be 10 mm, he may be back for surveillance colonoscopy in 3 years. If you estimate its size to be 9 mm, he may even be exempt from undergoing surveillance colonoscopy [11]. This makes a big difference in terms of the burden for patients, physicians, and healthcare systems. Furthermore, inconsistency in size estimation may affect treatment methods. Therefore, to deliver trustworthy endoscopy practice, we need to be very meticulous in polyp size estimation.
An emerging and promising anticancer strategy: colonization of engineered <i>Staphylococcus epidermidis</i>
Authors: Yanyan Liu, Yulong Cai
Journal: MedComm (2024)

Chen et al. 1 proposed an emerging and promising anticancer strategy that utilizes engineered skin bacteria to treat or prevent melanoma.The research shed light on the potential of microbiome to modulate host immunity and offered novel insights into the application of commensal microorganisms in human diseases.After a long period of coevolution, humans live in symbiosis with a variety of microorganisms, including gut microbes, skin symbionts, fungi, and viruses.Among them, skin microorganisms are a complex group containing bacteria, fungi, and viruses, which are involved in constituting the first protective barrier for humans. 2 It is worth mentioning that symbiotic bacteria have two roles that should not be overlooked: they are involved in the regulation of the local or systemic immune environment, and bacterial proteins can induce specific immune responses. 3or instance, in 2012, a study reported that the skin microbiota can actively control local inflammatory responses and regulate resident T lymphocyte function. 4Moreover, utilizing the immune function of the body is one of the significant tumor therapies.Based on these understandings, we would raise the question, could these interactions be used for antitumor therapy?Prof. Michael A. Fischbach's group from Stanford University explored this question and gave us the answer (Figure 1). 1 Staphylococcus epidermidis is a ubiquitous bacterium that colonizes the human skin and plays a significant
Deciphering tumor microenvironment: CXCL9 and SPP1 as crucial determinants of tumor-associated macrophage polarity and prognostic indicators
Authors: Xinming Su, Chenhao Liang, Ruixiu Chen, Shiwei Duan
Journal: Molecular Cancer (2024)

Abstract The tumor microenvironment (TME) is an intricate system comprised of tumor cells and the surrounding cellular and non-cellular components, exerting a pivotal influence on the initiation and progression of tumors. Exhibiting dynamic and diverse compositions as well as functional states across various tumors and patients, a profound comprehension of its specific internal interactions is indispensable for formulating efficacious anti-cancer treatment strategies. Extensive interactions among various immune cell types within the TME are well-documented, with their phenotypes and abundances closely linked to clinical prognoses. TME research is progressing towards greater complexity and precision, yet, to date, no representative TME biomarkers suitable for clinical applications have been definitively identified and validated. In a recent study, the collaborative actions of CXCL9 and SPP1 (CXCL9:SPP1) were found to collectively dictate the polarity of tumor-associated macrophages (TAMs) within the TME, exerting profound effects on tumor progression and treatment responses. The mutually exclusive expression of CXCL9:SPP1 in the TME not only governs TAM polarity but also exhibits strong correlations with immune cell profiles, antitumor factors, and patient outcomes, significantly influencing prognosis. This article consolidates the significance and prospects of CXCL9:SPP1 as a novel indicator for tumor development and prognosis, while also proposing future research directions and addressing potential challenges in this promising field.
Re: Randleman et al.: Subclinical keratoconus detection and characterization using motion tracking (Ophthalmology. 2023; Oct 13 :S0161-6420(23)00753-4. 2023 doi: 10.1016/j.ophtha.2023.10.011)
Authors: Mathew Francis, Abhijit Sinha Roy
Journal: Ophthalmology (2024)
A systematic review and qualitative research synthesis of the lived experiences and coping of transgender and gender diverse youth 18 years or younger
Authors: Kristiina Tyni, Matilda Wurm, Thomas Nordström, Anna Sofia Bratt
Journal: International Journal of Transgender Health (2024)

Research on the daily experiences of transgender and gender diverse (TGD) youth 18 years or younger is limited, making it essential to gain a comprehensive understanding of their internal and external experiences related to gender identity.
Modeling of A Bioengineered Immunomodulating Microenvironment for Cell Therapy
Authors: Simone Capuani, Jocelyn Nikita Campa‐Carranza, Nathanael Hernandez, Corrine Ying Xuan Chua, Alessandro Grattoni
Journal: Advanced Healthcare Materials (2024)

Abstract Cell delivery and encapsulation platforms are under development for the treatment of Type 1 Diabetes among other diseases. For effective cell engraftment, these platforms require establishing an immune‐protected microenvironment as well as adequate vascularization and oxygen supply to meet the metabolic demands of the therapeutic cells. Current platforms rely on 1) immune isolating barriers and indirect vascularization or 2) direct vascularization with local or systemic delivery of immune modulatory molecules. Supported by experimental data, here a broadly applicable predictive computational model capable of recapitulating both encapsulation strategies is developed. The model is employed to comparatively study the oxygen concentration at different levels of vascularization, transplanted cell density, and spatial distribution, as well as with codelivered adjuvant cells. The model is then validated to be predictive of experimental results of oxygen pressure and local and systemic drug biodistribution in a direct vascularization device with local immunosuppressant delivery. The model highlights that dense vascularization can minimize cell hypoxia while allowing for high cell loading density. In contrast, lower levels of vascularization allow for better drug localization reducing systemic dissemination. Overall, it is shown that this model can serve as a valuable tool for the development and optimization of platform technologies for cell encapsulation.
Standardised training for endoscopic mucosal resection of large non-pedunculated colorectal polyps to reduce recurrence (*STAR-LNPCP study): a multicentre cluster randomised trial
Authors: Lonne W T Meulen, Roel M M Bogie, Peter D Siersema, Bjorn Winkens, Marije S Vlug, Frank H J Wolfhagen, Martine Baven-Pronk, Michael van der Voorn, Matthijs P Schwartz, Lauran Vogelaar, Wouter H de Vos tot Nederveen Cappel, Tom C J Seerden, Wouter L Hazen, Ruud W M Schrauwen, Lorenza Alvarez Herrero, Ramon-Michel M Schreuder, Annick B van Nunen, Esther Stoop, Gijs J de Bruin, Philip Bos, Willem A Marsman, Edith Kuiper, Marc de Bièvre, Yasser A Alderlieste, Robert Roomer, John Groen, Marloes Bargeman, Monique E van Leerdam, Linda Roberts-Bos, Femke Boersma, Karsten Thurnau, Roland S de Vries, Jos M Ramaker, Frank P Vleggaar, Rogier J de Ridder, María Pellisé, Michael J Bourke, Ad A M Masclee, Leon M G Moons
Journal: Gut (2024)

Objective Endoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with an early recurrence rate of up to 30%. We evaluated whether standardised EMR training could reduce recurrence rates in Dutch community hospitals. Design In this multicentre cluster randomised trial, 59 endoscopists from 30 hospitals were randomly assigned to the intervention group (e-learning and 2-day training including hands-on session) or control group. From April 2019 to August 2021, all consecutive EMR-treated LNPCPs were included. Primary endpoint was recurrence rate after 6 months. Results A total of 1412 LNPCPs were included; 699 in the intervention group and 713 in the control group (median size 30 mm vs 30 mm, 45% vs 52% size, morphology, site and access (SMSA) score IV, 64% vs 64% proximal location). Recurrence rates were lower in the intervention group compared with controls (13% vs 25%, OR 0.43; 95% CI 0.23 to 0.78; p=0.005) with similar complication rates (8% vs 9%, OR 0.93; 95% CI 0.64 to 1.36; p=0.720). Recurrences were more often unifocal in the intervention group (92% vs 76%; p=0.006). In sensitivity analysis, the benefit of the intervention on recurrence rate was only observed in the 20–40 mm LNPCPs (5% vs 20% in 20–29 mm, p=0.001; 10% vs 21% in 30–39 mm, p=0.013) but less evident in ≥40 mm LNPCPs (24% vs 31%; p=0.151). In a post hoc analysis, the training effect was maintained in the study group, while in the control group the recurrence rate remained high. Conclusion A compact standardised EMR training for LNPCPs significantly reduced recurrences in community hospitals. This strongly argues for a national dedicated training programme for endoscopists performing EMR of ≥20 mm LNPCPs. Interestingly, in sensitivity analysis, this benefit was limited for LNPCPs ≥40 mm. Trial registration number NTR7477.
Retrospective analysis of referrals for hypoxic challenge testing in children born preterm
Authors: Anna Howells, Mollie Riley, Martin Samuels, Paul Aurora
Journal: Thorax (2024)

Introduction Children with a history of bronchopulmonary dysplasia (BPD) may be at risk of hypoxaemia at altitude, such as during air travel. We have performed preflight hypoxic challenge testing (HCT) since 2006, incorporating British Thoracic Society (BTS) guidance since 2011, to determine which children may require oxygen during air travel. Aims We aimed to compare the outcome of HCTs in children with a history of BPD who met the 2011 BTS criteria and those who did not and, in addition to this, to interrogate the data for factors that may predict the outcome of HCT in this population. Methods We performed a retrospective analysis of data from HCTs of children with a history of BPD referred 2006–2020. Cases were excluded if the patient had a respiratory comorbidity, was still on oxygen therapy, if the test was a repeat or if the clinical record was incomplete. Descriptive and univariate analysis of the data was performed, and a binary logistic regression model was fitted. Results There were 79 HCTs, of which 24/79 (30%) did not meet BTS 2011 guidelines referral criteria. The analysis showed a greater proportion of desaturation in the group that did not meet criteria: 46% vs 27% (no statistical significance). Baseline oxygen saturations were higher in those who did not require oxygen during HCT and this variable was significant when adjusted for confounders. Conclusions This study found that the current criteria for referral for preflight testing may incorrectly identify those most at risk and highlights the need for further investigation to ensure those most at risk are being assessed prior to air travel.
Unsupervised spatially embedded deep representation of spatial transcriptomics
Authors: Hang Xu, Huazhu Fu, Yahui Long, Kok Siong Ang, Raman Sethi, Kelvin Chong, Mengwei Li, Rom Uddamvathanak, Hong Kai Lee, Jingjing Ling, Ao Chen, Ling Shao, Longqi Liu, Jinmiao Chen
Journal: Genome Medicine (2024)

Abstract Optimal integration of transcriptomics data and associated spatial information is essential towards fully exploiting spatial transcriptomics to dissect tissue heterogeneity and map out inter-cellular communications. We present SEDR, which uses a deep autoencoder coupled with a masked self-supervised learning mechanism to construct a low-dimensional latent representation of gene expression, which is then simultaneously embedded with the corresponding spatial information through a variational graph autoencoder. SEDR achieved higher clustering performance on manually annotated 10 × Visium datasets and better scalability on high-resolution spatial transcriptomics datasets than existing methods. Additionally, we show SEDR’s ability to impute and denoise gene expression (URL: https://github.com/JinmiaoChenLab/SEDR/ ).
Dopamine-independent effect of rewards on choices through hidden-state inference
Authors: Marta Blanco-Pozo, Thomas Akam, Mark E. Walton
Journal: Nature Neuroscience (2024)

Abstract Dopamine is implicated in adaptive behavior through reward prediction error (RPE) signals that update value estimates. There is also accumulating evidence that animals in structured environments can use inference processes to facilitate behavioral flexibility. However, it is unclear how these two accounts of reward-guided decision-making should be integrated. Using a two-step task for mice, we show that dopamine reports RPEs using value information inferred from task structure knowledge, alongside information about reward rate and movement. Nonetheless, although rewards strongly influenced choices and dopamine activity, neither activating nor inhibiting dopamine neurons at trial outcome affected future choice. These data were recapitulated by a neural network model where cortex learned to track hidden task states by predicting observations, while basal ganglia learned values and actions via RPEs. This shows that the influence of rewards on choices can stem from dopamine-independent information they convey about the world’s state, not the dopaminergic RPEs they produce.