tbuckley/cabot-search huggingface dataset:
A Phase I Study of Acapatamab, a Half-life Extended, PSMA-Targeting Bispecific T-cell Engager for Metastatic Castration-Resistant Prostate Cancer
Authors: Tanya Dorff, Lisa G. Horvath, Karen Autio, Alice Bernard-Tessier, Matthew B. Rettig, Jean-Pascal Machiels, Mehmet A. Bilen, Martijn P. Lolkema, Nabil Adra, Sylvie Rottey, Richard Greil, Nobuaki Matsubara, Daniel S.W. Tan, Alvin Wong, Hiroji Uemura, Charlotte Lemech, Johannes Meran, Youfei Yu, Mukul Minocha, Mason McComb, Hweixian Leong Penny, Vinita Gupta, Xuguang Hu, Gabor Jurida, Hosein Kouros-Mehr, Margit M. Janát-Amsbury, Tobias Eggert, Ben Tran
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Safety and efficacy of acapatamab, a prostate-specific membrane antigen (PSMA) x CD3 bispecific T-cell engager were evaluated in a first-in-human study in metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods: Patients with mCRPC refractory to androgen receptor pathway inhibitor therapy and taxane-based chemotherapy received target acapatamab doses ranging from 0.003 to 0.9 mg in dose exploration (seven dose levels) and 0.3 mg (recommended phase II dose) in dose expansion intravenously every 2 weeks. Safety (primary objective), pharmacokinetics, and antitumor activity (secondary objectives) were assessed. Results: In all, 133 patients (dose exploration, n = 77; dose expansion, n = 56) received acapatamab. Cytokine release syndrome (CRS) was the most common treatment-emergent adverse event seen in 97.4% and 98.2% of patients in dose exploration and dose expansion, respectively; grade ≥ 3 was seen in 23.4% and 16.1%, respectively. Most CRS events were seen in treatment cycle 1; incidence and severity decreased at/beyond cycle 2. In dose expansion, confirmed prostate-specific antigen (PSA) responses (PSA50) were seen in 30.4% of patients and radiographic partial responses in 7.4% (Response Evaluation Criteria in Solid Tumors 1.1). Median PSA progression-free survival (PFS) was 3.3 months [95% confidence interval (CI): 3.0–4.9], radiographic PFS per Prostate Cancer Clinical Trials Working Group 3 was 3.7 months (95% CI: 2.0–5.4). Acapatamab induced T-cell activation and increased cytokine production several-fold within 24 hours of initiation. Treatment-emergent antidrug antibodies were detected in 55% and impacted serum exposures in 36% of patients in dose expansion. Conclusions: Acapatamab was safe and tolerated and had a manageable CRS profile. Preliminary signs of efficacy with limited durable antitumor activity were observed. Acapatamab demonstrated pharmacokinetic and pharmacodynamic activity.
Authors' Reply: Platelet Count, Platelet Volume and CKD
Authors: Rajshekhar Kore, Dharmik Jadvani, John M. Arthur, Nishank Jain
Journal: Journal of the American Society of Nephrology (2024)

1Division of Nephrology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 2Renal Section, Central Arkansas Veterans Affairs Medical Center, Little Rock, Arkansas Correspondence: Dr. Nishank Jain, Division of Nephrology, Department of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 501, Little Rock, AR 72205. Email: [email protected] See related letter to the editor, "Platelet Count, Platelet Volume and CKD," on pages 249, and original article, "Platelet Count and Platelet Volume in Patients with CKD," in Vol. 34, Iss. 11, 1772–1775.
Exploring substrate–microbe interactions: a metabiotic approach toward developing targeted synbiotic compositions
Authors: Bodo Speckmann, Ellen Ehring, Jiaying Hu, Ana Rodriguez Mateos
Journal: Gut Microbes (2024)

Gut microbiota is an important modulator of human health and contributes to high inter-individual variation in response to food and pharmaceutical ingredients. The clinical outcomes of interventions with prebiotics, probiotics, and synbiotics have been mixed and often unpredictable, arguing for novel approaches for developing microbiome-targeted therapeutics. Here, we review how the gut microbiota determines the fate of and individual responses to dietary and xenobiotic compounds via its immense metabolic potential. We highlight that microbial metabolites play a crucial role as targetable mediators in the microbiota-host health relationship. With this in mind, we expand the concept of synbiotics beyond prebiotics' role in facilitating growth and engraftment of probiotics, by focusing on microbial metabolism as a vital mode of action thereof. Consequently, we discuss synbiotic compositions that enable the guided metabolism of dietary or co-formulated ingredients by specific microbes leading to target molecules with beneficial functions. A workflow to develop novel synbiotics is presented, including the selection of promising target metabolites (e.g. equol, urolithin A, spermidine, indole-3 derivatives), identification of suitable substrates and producer strains applying bioinformatic tools, gut models, and eventually human trials.
Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study
Authors: Estella de Jong, Roel Genders, Catherine A. Harwood, Adèle C. Green, Elsemieke I. Plasmeijer, Charlotte Proby, Edward Geissler, Carla Ferrándiz-Pulido, Emilie Ducroux, Sylvie Euvrard, Alexandra Geusau, Karin Jahn-Bassler, Liliane Borik-Heil, Emõke Rácz, Mirjam Nägeli, Günther F.L. Hofbauer, Stefano Piaserico, Irene Russo, Lorna Mackintosh, João Borges-Costa, Maria Angeliki-Gkini, Elisa Zavattaro, Paola Savoia, Beata Imko-Walszuk, Alicja Dębska-Slizień, Marjan Garmyn, Sofie van Kelst, Jan Ricar, Petra Cetkovska, Rubeta Matin, Ayşe Tülin Güleç, Deniz Seçkin, Chinedu Anthony Anene, Walmar R.P. Oliveira, Marius Rademaker, Jelle Goeman, Nan van Geloven, Emily Ruiz, Fadi Murad, Emily Karn, Chrysalyne D. Schmults, Jan Nico Bouwes Bavinck
Journal: Journal of the American Academy of Dermatology (2024)

Introduction Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous-cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. Methods In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. Results Of 514 SOTRs who presented with 623 primary cSCCs, 37 developed metastases with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size >2cm, clinical ulceration, poor differentiation grade, perineural invasion and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9% – 68.4%). Conclusions SOTRs have a high risk of cSCC metastases and well-established clinical and histological risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.
Methylation of GPRC5A promotes liver metastasis and docetaxel resistance through activating mTOR signaling pathway in triple negative breast cancer
Authors: Xueqi Ou, Yeru Tan, Jindong Xie, Jingping Yuan, Xinpei Deng, Ruonan Shao, Cailu Song, Xi Cao, Xiaoming Xie, Rongfang He, Yuehua Li, Hailin Tang
Journal: Drug Resistance Updates (2024)

This study aims to explore the function and mechanism of G Protein-coupled receptor class C group 5 member A (GPRC5A) in docetaxel-resistance and liver metastasis of breast cancer.
Psychedelics for alzheimer's disease-related dementia: Unveiling therapeutic possibilities and pathways
Authors: Jitendra Kumar Sinha, Anchal Trisal, Shampa Ghosh, Saurabh Gupta, Krishna Kumar Singh, Sung Soo Han, Madhumita Mahapatra, Mosleh Mohammad Abomughaid, Ali M. Abomughayedh, Abdulmajeed G. Almutary, Danish Iqbal, Rakesh Bhaskar, Prabhu Chandra Mishra, Saurabh Kumar Jha, Niraj Kumar Jha, Abhishek Kumar Singh
Journal: Ageing Research Reviews (2024)
Turning Threat to Therapy: A Nanozyme‐Patch in Surgical Bed for Convenient Tumor Vaccination by Sustained In Situ Catalysis
Authors: Zhaohui Wang, Min Dong, Yuhang Pan, Lu Zhang, Haozhuo Lei, Yuanzhe Zheng, Yanbin Shi, Shuang Liu, Nan Li, Yalong Wang
Journal: Advanced Healthcare Materials (2024)

Complete surgical resection of tumor is difficult as the invasiveness of cancer, making the residual tumor a lethal threat to patients. The situation is deteriorated by the immune suppression state after surgery, which further nourishes tumor recurrence and metastasis. Immunotherapy is promising to combat tumor metastasis, but is limited by severe toxicity of traditional immunostimulants and complexity of multiple functional units. Here, it is reported that the simple "trans-surgical bed" delivery of Cu
Unadjusted Lower Limit of Normal for Airflow Obstruction
Authors: Surya P. Bhatt, Sandeep Bodduluri, Arie Nakhmani, Elizabeth C. Oelsner
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Unadjusted Lower Limit of Normal for Airflow Obstruction." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Conservation of Affinity Rather Than Sequence Underlies a Dynamic Evolution of the Motif-Mediated p53/MDM2 Interaction in Ray-Finned Fishes
Authors: Filip Mihalič, Dahiana Arcila, Mats E Pettersson, Pouria Farkhondehkish, Eva Andersson, Leif Andersson, Ricardo Betancur-R, Per Jemth
Journal: Molecular Biology and Evolution (2024)

Abstract The transcription factor and cell cycle regulator p53 is marked for degradation by the ubiquitin ligase MDM2. The interaction between these 2 proteins is mediated by a conserved binding motif in the disordered p53 transactivation domain (p53TAD) and the folded SWIB domain in MDM2. The conserved motif in p53TAD from zebrafish displays a 20-fold weaker interaction with MDM2, compared to the interaction in human and chicken. To investigate this apparent difference, we tracked the molecular evolution of the p53TAD/MDM2 interaction among ray-finned fishes (Actinopterygii), the largest vertebrate clade. Intriguingly, phylogenetic analyses, ancestral sequence reconstructions, and binding experiments showed that different loss-of-affinity changes in the canonical binding motif within p53TAD have occurred repeatedly and convergently in different fish lineages, resulting in relatively low extant affinities (KD = 0.5 to 5 μM). However, for 11 different fish p53TAD/MDM2 interactions, nonconserved regions flanking the canonical motif increased the affinity 4- to 73-fold to be on par with the human interaction. Our findings suggest that compensating changes at conserved and nonconserved positions within the motif, as well as in flanking regions of low conservation, underlie a stabilizing selection of “functional affinity” in the p53TAD/MDM2 interaction. Such interplay complicates bioinformatic prediction of binding and calls for experimental validation. Motif-mediated protein–protein interactions involving short binding motifs and folded interaction domains are very common across multicellular life. It is likely that the evolution of affinity in motif-mediated interactions often involves an interplay between specific interactions made by conserved motif residues and nonspecific interactions by nonconserved disordered regions.
Supramolecular prodrug-like nanotheranostics with dynamic and activatable nature for synergistic photothermal immunotherapy of metastatic cancer
Authors: Yajie Li, Xueluer Mu, Wenbi Feng, Min Gao, Zigeng Wang, Xue Bai, Xiangru Ren, Yingxi Lu, Xianfeng Zhou
Journal: Journal of Controlled Release (2024)
“ERS/ESTS/ESTRO/ESR/ESTI/EFOMP statement on management of incidental findings from low dose CT screening for lung cancer.” E.L. O'Dowd, I. Tietzova, E. Bartlett,<i>et al</i>.<i>Eur Respir J</i>2023; 62: 2300533.
Journal: European Respiratory Journal (2024)
Towards a patient-centred definition for atopic dermatitis flare: a qualitative study of adults with atopic dermatitis
Authors: Katie N Dainty, Isabelle J C Thibau, Krystle Amog, Aaron M Drucker, Matthew Wyke, Wendy Smith Begolka
Journal: British Journal of Dermatology (2024)

Abstract Background The term ‘flare’ is used across multiple diseases, including atopic dermatitis (AD), to describe increased disease activity. While several definitions of an AD flare have been proposed, no single definition of AD flare is widely accepted and it is unclear what the term ‘AD flare’ means from the patient perspective. Objectives To understand AD flares from the adult patient perspective and to explore how adults with AD define an AD flare. Methods Participants were adults with AD recruited from the National Eczema Association Ambassadors programme, a volunteer patient-engagement programme. They participated in online focus groups to discuss how they describe AD flares from their perspective, how they define its start and stop, and how they relate to existing definitions of flare. Using a grounded theory approach, transcripts were analysed and coded using an iterative process to identify concepts to support a patient-centred conceptual framework of ‘flare’. Results Six 90-min focus groups of 3–8 participants each were conducted with 29 US adults (≥ 18 years of age) with AD who had at least one self-reported AD flare in the past year. When participants were presented with examples of previously published definitions of AD flare, participants found them problematic and unrelatable. Specifically, they felt that flare is hard to quantify or put on a numerical scale, definitions cannot solely be about skin symptoms and clinical verbiage does not resonate with patients’ lived experiences. Concepts identified by patients as important to a definition of flare were changes from patient’s baseline/patient’s normal, mental/emotional/social consequences, physical changes in skin, attention needed/all-consuming focus, itch–scratch–burn cycle and control/loss of control/quality of life. Figuring out the trigger that initiated a flare was an underlying concept of the experience of flare but was not considered a contributor to the definition. Conclusions The results highlight the complexity and diversity of AD flare experiences from the adult patient perspective. Previously published definitions of AD flares did not resonate with patients, suggesting a need for a patient-centred flare definition to support care conversations and AD management.
Long-term drug survival of adalimumab, infliximab, secukinumab and ustekinumab in hidradenitis suppurativa: a Danish nationwide cohort study
Authors: Hans Christian Ring, Jonathan Thorsen, Brian Kirby, John R Ingram, Nana Aviaaja Lippert Rosenø, Nikolaj Holgersen, Valdemar W Nielsen, David Nikolai Thein Aagaard, Julia-Tatjana Maul, Jashin J Wu, Jacob P Thyssen, Alexander Egeberg, Simon F Thomsen
Journal: British Journal of Dermatology (2024)

This nationwide cohort study included 452 patients (873 treatment series) and reported drug survival data on patients with hidradenitis suppurativa treated with biologics such as adalimumab, infliximab, ustekinumab and secukinumab. The median drug survival time for adalimumab was approximately 8 months, but bio-naïve patients had a significantly longer drug survival time compared with non-naïve patients.
Positive Selection Drives <i>cis-</i>regulatory Evolution Across the Threespine Stickleback Y Chromosome
Authors: Daniel E Shaw, Alice Shanfelter Naftaly, Michael A White
Journal: Molecular Biology and Evolution (2024)

Abstract Allele-specific gene expression evolves rapidly on heteromorphic sex chromosomes. Over time, the accumulation of mutations on the Y chromosome leads to widespread loss of gametolog expression, relative to the X chromosome. It remains unclear if expression evolution on degrading Y chromosomes is primarily driven by mutations that accumulate through processes of selective interference, or if positive selection can also favor the down-regulation of coding regions on the Y chromosome that contain deleterious mutations. Identifying the relative rates of cis-regulatory sequence evolution across Y chromosomes has been challenging due to the limited number of reference assemblies. The threespine stickleback (Gasterosteus aculeatus) Y chromosome is an excellent model to identify how regulatory mutations accumulate on Y chromosomes due to its intermediate state of divergence from the X chromosome. A large number of Y-linked gametologs still exist across 3 differently aged evolutionary strata to test these hypotheses. We found that putative enhancer regions on the Y chromosome exhibited elevated substitution rates and decreased polymorphism when compared to nonfunctional sites, like intergenic regions and synonymous sites. This suggests that many cis-regulatory regions are under positive selection on the Y chromosome. This divergence was correlated with X-biased gametolog expression, indicating the loss of expression from the Y chromosome may be favored by selection. Our findings provide evidence that Y-linked cis-regulatory regions exhibit signs of positive selection quickly after the suppression of recombination and allow comparisons with recent theoretical models that suggest the rapid divergence of regulatory regions may be favored to mask deleterious mutations on the Y chromosome.
<i>Bridge</i>: A New Algorithm for Rooting Orthologous Genes in Large-Scale Evolutionary Analyses
Authors: Leonardo R S Campos, Sheyla Trefflich, Diego A A Morais, Danilo O Imparato, Vinicius S Chagas, Ricardo D’Oliveira Albanus, Rodrigo J S Dalmolin, Mauro A A Castro
Journal: Molecular Biology and Evolution (2024)

Orthology information has been used for searching patterns in high-dimensional data, allowing transferring functional information between species. The key concept behind this strategy is that orthologous genes share ancestry to some extent. While reconstructing the history of a single gene is feasible with the existing computational resources, the reconstruction of entire biological systems remains challenging. In this study, we present Bridge, a new algorithm designed to infer the evolutionary root of orthologous genes in large-scale evolutionary analyses. The Bridge algorithm infers the evolutionary root of a given gene based on the distribution of its orthologs in a species tree. The Bridge algorithm is implemented in R and can be used either to assess genetic changes across the evolutionary history of orthologous groups or to infer the onset of specific traits in a biological system.
Caring for babies born with epidermolysis bullosa
Authors: Celia Moss
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof Caring for babies born with epidermolysis bullosa Get access Celia Moss Celia Moss Conceptualization, Writing - original draft, Writing - review & editing Department of Dermatology, Birmingham Women's and Children's Hospitals NHS Foundation TrustUniversity of Birmingham College of Medical and Dental Sciences, Birmingham, UK Email: celia.moss@nhs.net https://orcid.org/0000-0003-1773-4011 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae048, https://doi.org/10.1093/bjd/ljae048 Published: 02 February 2024 Article history Received: 26 January 2024 Accepted: 26 January 2024 Published: 02 February 2024 Corrected and typeset: 04 March 2024
Breastfeeding decreases the risk of developing psoriasis through to early adulthood
Authors: Debojyoti Das, Joana Thimjo, Andrea Lebena, Annie Guo, Charlotta Enerbäck, Johnny Ludvigsson
Journal: British Journal of Dermatology (2024)

Abstract Background Psoriasis is a genetically determined systemic skin disease, although environmental trigger factors are required for disease manifestation. Some of these triggers, such as stress, infections and drug exposure, have been identified. Objectives To explore the role of early nutrition as a risk factor for the development of psoriasis. Methods Parents in the All Babies in Southeast Sweden (ABIS) prospective birth cohort (n = 16 415) answered questionnaires at birth and when their children were aged 1 and 3 years. A diagnosis of psoriasis was determined from the Swedish National Patient Register and National Drug Prescription Register. Statistical analyses were conducted using custom-written R scripts. Results Individuals breastfed for &amp;lt; 4 months and who received infant formula before 4 months of age had a higher risk of psoriasis [odds ratio (OR) 1.84 (P = 0.02) and OR 1.88 (P = 0.02), respectively]. At the 3-year follow-up, the increased consumption of fish, especially from the Baltic Sea, increased the risk of psoriasis (OR 9.61; P = 0.003). In addition, the risk of psoriasis increased following the consumption of a large volume of milk (OR 2.53; P = 0.04). Conclusions Our study underscores, for the first time, the impact of very early nutrition on the manifestation of psoriasis through early adulthood. Exclusive breastfeeding for 4 months appears to be protective.
Detection of α-papillomaviruses in extragenital cutaneous squamous cell carcinomas
Authors: Morgane Weiss, Valentine M Ferré, Lydia Deschamps, Diane Evrard, Clémentine Gonthier, Charlotte Charpentier, Florence Brunet-Possenti
Journal: British Journal of Dermatology (2024)

Previous studies have demonstrated that human papillomaviruses (HPVs) of the beta genus can contribute to the onset of cutaneous carcinomas in organ transplant recipients. In contrast, there are limited data related to the oncogenicity of alpha (α)-HPVs in the skin. Herein, we explore the characteristics of three cutaneous squamous cell carcinomas presenting α-HPV infection occurring in patients with HIV, in order to determine the role of α-HPV in these skin cancers.
Endoscopic ultrasound-guided access using a lumen-apposing metal stent for the management of duodenal bleeding in a Roux-en-Y anatomy after gastric bypass
Authors: Anna Fichtl, Leonard Elad, Marko Kornmann, Thomas Seufferlein, Martin Müller, Martin Wagner, Benjamin M. Walter
Journal: Endoscopy (2024)

A 54-year-old woman with obesity presented to our hospital with symptoms of severe gastrointestinal bleeding. She had undergone bariatric robotic Roux-en-Y gastric bypass 4 months previously. Endoscopic examination revealed no signs of active bleeding in the gastric remnant, but signs of upper gastrointestinal bleeding were evident through the afferent jejunal loop, leading us to suspect that the bleeding originated from the bypassed stomach. After interdisciplinary discussion we decided on an endoscopic ultrasound (EUS)-guided approach to re-enter the bypassed stomach ([Video 1]).
Endoscopic ultrasound gastroenterostomy: how to avoid inadvertent gastrocolostomy
Authors: Jimil Shah, Abhirup Chatterjee, Vaneet Jearth, Anupam K. Singh
Journal: Endoscopy (2024)

Endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE) is a commonly used modality in patients with gastric outlet obstruction, with results equivalent to surgical gastrojejunostomy [1] [2]. Inadvertent gastrocolostomy is a rare but major complication of EUS-GE [3]. As the transverse colon is a mobile structure, it can overlap the jejunal loop, and failure to identify this can lead to inadvertent gastrocolostomy [3].