tbuckley/cabot-search huggingface dataset:
Monokine induced by gamma interferon levels in plasma might be a diagnostic marker of Hydroa vaccniforme lymphoproliferative disorder systemic form
Authors: Tomoko Miyake, Takenobu Yamamoto, Yoji Hirai, Takahide Takahashi, Takuya Furuhashi, Hisashi Nomura, Yoshio Kawakami, Shin Morizane
Journal: Journal of the American Academy of Dermatology (2024)
A phase III randomized trial on the addition of a contact x-ray brachytherapy boost to standard neoadjuvant chemo-radiotherapy for organ preservation in early rectal adenocarcinoma: 5 year results of the OPERA trial
Authors: D. Baron, T. Pace Loscos, R. Schiappa, N. Barbet, E. Dost, S. Ben Dhia, S. Soltani, L. Mineur, I. Martel, S. Horn, C. Picardi, A. Stewart, E. Cotte, R. Coquard, G. Baudin, L. Evesque, A. Dhadda, A. Sun Myint, J.P. Gérard, J. Doyen
Journal: Annals of Oncology (2024)
Circulating tumor DNA status and dynamics predict recurrence in patients with resected extrahepatic cholangiocarcinoma
Authors: Changhoon Yoo, Hyehyun Jeong, Jae Ho Jeong, Kyu-pyo Kim, Seonmin Lee, Baek-Yeol Ryoo, Dae Wook Hwang, Jae Hoon Lee, Deog-Bog Moon, Ki-Hun Kim, Sang Soo Lee, Tae Jun Song, Dongwook Oh, Myung Ah Lee, Hong Jae Chon, Ji Sung Lee, George Laliotis, Samuel Rivero-Hinojosa, Erik Spickard, Derrick Renner, Punashi Dutta, Charuta C. Palsuledesai, Shruti Sharma, Meenakshi Malhotra, Adham Jurdi, Minetta C. Liu
Journal: Journal of Hepatology (2024)

Surgery is the only curative therapeutic option for resectable extrahepatic cholangiocarcinoma (eCCA), but recurrence is common, and prognosis is poor. There is an unmet clinical need for improved decision-making regarding adjuvant chemotherapy (ACT). Here we evaluated the usefulness of monitoring longitudinal circulating tumor DNA (ctDNA) for minimal residual disease (MRD) in patients of the STAMP trial, which compares the efficacy of adjuvant capecitabine (CAP) versus gemcitabine plus cisplatin (GemCis).
Low-dose interleukin-2 in birch pollen allergy: a phase-2 randomized double-blind placebo-controlled trial
Authors: Michelle Rosenzwajg, Alina Gherasim, Franck Dietsch, Marine Beck, Nathalie Domis, Roberta Lorenzon, Yannick Chantran, Bertrand Bellier, Eric Vicaut, Angele Soria, Frederic de Blay, David Klatzmann
Journal: Journal of Allergy and Clinical Immunology (2024)
Interventions to ensure access to and continuity of HIV care for international migrants: an evidence synthesis
Authors: Alena Kamenshchikova, Charlotte M M Peters, Christiana Nöstlinger, Brian Rice, Nathan Ford, Giovanni Ravasi, Fiona Burns, Milosz Parczewski, Christian J P A Hoebe, Nicole Dukers, Farah Seedat, Antons Mozalevskis, Linda-Gail Bekker, Jean Berchmans Tugirimana, Weiming Tang, Gifty Marley, Denis Onyango, Monica C Thormann Peynado, Teymur Noori, Sally Hargreaves
Journal: The Lancet HIV (2024)
Humanising and optimising HIV health care for refugees and asylum seekers
Authors: Claudia P Cortes, Omar Sued, William C W Wong, Annick Borquez, Charles Ssonko, Miłosz Parczewski, Jocelyn DeJong, Vonthanak Saphonn, Animesh Sinha, Báltica Cabieses
Journal: The Lancet HIV (2024)
CSF proteins of inflammation, proteolysis and lipid transport define preclinical AD and progression to AD dementia in cognitively unimpaired individuals
Authors: Marta Del Campo, Carlos Quesada, Lisa Vermunt, Carel F W Peeters, Yanaika S Hok-A-Hin, Calvin Trieu, Anouk den Braber, Inge M W Verberk, Pieter J Visser, Betty M Tijms, Wiesje M van der Flier, Charlotte E Teunissen
Journal: Molecular Neurodegeneration (2024)

This preclinical AD CSF proteome study identified a panel of 12-CSF markers detecting amyloid positivity and clinical progression to AD with high accuracy; some of these CSF proteins related to immune function, neurotrophic processes, energy metabolism and endolysosomal functioning (e.g., ITGB2, CLEC5A, IGFBP-1, CST3) changed before amyloid positivity is established.
KRAS mutations promote the intratumoral colonization of enterotoxigenic bacteroides fragilis in colorectal cancer through the regulation of the miRNA3655/SURF6/IRF7/IFNβ axis
Authors: Yizhen Chen, Shaolin Liu, Song Tan, Yuanyuan Zheng, Yifan Chen, Changshun Yang, Shengtao Lin, Yulong Mi, Weihua Li
Journal: Gut Microbes (2024)

KRAS mutations are associated with poor prognosis in colorectal cancer (CRC). Although the association between the gut microbiota and CRC has been extensively documented, it is unclear whether KRAS mutations can regulate the gut microbiota. Metagenomics has identified changes in the diversity of the gut microbiota in CRC due to KRAS mutations. Specifically, KRAS mutations positively correlate with the abundance of the bacteroides. Understanding how to regulate the classic carcinogenic bacterium within the bacteroides, such as enterotoxigenic bacteroides fragilis (ETBF), to enhance treatment efficacy of tumors is a key focus of research. Mechanistically, we found that the reduction of miR3655 is indispensable for KRAS mutation-promoted proliferation of CRC and the abundance of ETBF. miR3655 targets SURF6 to inhibit its transcription. Further transcriptomic sequencing revealed that SURF6 promotes intratumoral colonization of ETBF in CRC by inhibiting the nuclear translocation and transcription levels of the IRF7, affecting the activation of the IFNβ promoter. Regulating miR3655 and SURF6 can promote IFNβ secretion in CRC, directly killing ETBF. These data indicate that KRAS mutations affect the intratumoral colonization of ETBF in CRC through the miR3655/SURF6/IRF7/IFNβ axis. This provides new potential strategies for treating CRC associated with KRAS mutations or high levels of ETBF.
Reverse engineering the Gut-Brain Axis and microbiome-metabolomics for symbiotic/pathogenic balance in neurodegenerative diseases
Authors: Muhammad Usman Munir, Syed Aoun Ali, Ka Hang Karen Chung, Aleksandr Kakinen, Ibrahim Javed, Thomas Paul Davis
Journal: Gut Microbes (2024)

Deciphering the molecular communications along the gut-brain axis can help in understanding the pathophysiology of neurodegenerative diseases and exploiting the gut microbiome for therapeutics. However, gut microbes and their metabolites have a multifaceted role in mediating both brain physiology and neurodegenerative pathology. There is a lack of understanding of how and when this role is tipped in neurodegenerative diseases and what are those contributing factors, both at local (gut) and distal (neuronal) levels, that drive this imbalance. Here we have reviewed the gut microbiome and its metabolites in the context of the gut-brain axis and summarized how different factors such as gut-microbial diversity, their metabolites, the role of the native immune system and the integrity of gut epithelial and blood-brain barriers are interconnected and collectively define the involvement of gut-microbiome in neurodegenerative pathologies. It also underlines the need for multidisciplinary tools and animal models to simultaneously reflect on many of these factors and to better correlate with clinical observations and data obtained from human biopsies and fecal samples. Harnessing the gut-brain axis will herald a paradigm shift in medicine for neurodegenerative diseases and aging, emphasizing the significance of the microbiome in the broader spectrum of health and disease.
Iparomlimab (QL1604) in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) unresectable or metastatic solid tumors: a pivotal, single-arm, multicenter, phase II trial
Authors: Feng Bi, Jian Dong, Chuan Jin, Zuoxing Niu, Wenhui Yang, Yifu He, Dajun Yu, Meili Sun, Teng Wang, Xianli Yin, Ruixing Zhang, Kehe Chen, Keming Wang, Zhiwu Wang, Wei Li, Zhongtao Zhang, Hangyu Zhang, Qunyi Guo, Xin Wang, Lei Han, Xizhi Zhang, Wei Shen, Liangming Zhang, Jieer Ying, Miao Wu, Weiguo Hu, Zeng Li, Xiaofen Li, Wenlei Feng, Baihui Zhang, Lingyan Li, Xiaoyan Kang, Weijian Guo
Journal: Journal of Hematology & Oncology (2024)

Though several anti-PD-1/PD-L1 antibodies approved for monotherapy in microsatellite instability-high or mismatch repair-deficient unresectable/metastatic solid tumors, novel immunotherapy with better anti-tumor activity is needed in clinic. In this single-arm, multicenter, pivotal, phase II study, patients received iparomlimab (a novel humanized anti-PD-1 mAb, 200 mg or 3 mg/kg for patients with body weight < 40 kg, IV, Q3W) until disease progression, intolerable toxicities, withdrawal of consent, death, or up to 2 years. The primary endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC). Totally, 120 patients were enrolled, of whom 60 patients failed from prior standard therapy, were enrolled in the full analysis set (FAS). As of Jan 20, 2024, the confirmed ORR per IRRC in FAS were 50.0% (30/60; 95% CI 36.8–63.2%) patients, including 4 (6.7%) complete response (CR) and 26 (43.3%) partial response (PR). In colorectal cancer (CRC) patients in FAS, the ORR reached 57.9% (22/38; 95% CI 40.8–73.7%) per IRRC, with 3 (7.9%) CR and 19 (50.0%) PR. Furtherly, the ORRs in liver metastatic or non-liver metastatic CRC patients were 52.9% (9/17, 95% CI 27.8–77.0%) vs 61.9% (13/21, 95% CI 38.4%–81.9%). The incidence of TRAE was 90.8% (any grade) and 20.8% (grade ≥ 3). Immune-related adverse events occurred in 33.3% (any grade) and 5.0% (grade ≥ 3) of patients. No iparomlimab-related death occurred. Iparomlimab presented encouraging antitumor activity with durable response and tolerable safety profile. Trial registration ClinicalTrials.gov Identifier: NCT04326829.
Bridging the gender, climate, and health gap: the road to COP29
Authors: Kim Robin van Daalen, Laura Jung, Sara Dada, Razan Othman, Alanna Barrios-Ruiz, Grace Zurielle Malolos, Kai-Ti Wu, Ana Garza-Salas, Salma El-Gamal, Tarek Ezzine, Parnian Khorsand, Arthur Wyns, Blanca Paniello-Castillo, Sophie Gepp, Maisoon Chowdhury, Ander Santamarta Zamorano, Jess Beagley, Clare Oliver-Williams, Ramit Debnath, Ronita Bardhan, Nicole de Paula, Alexandra Phelan, Rachel Lowe
Journal: The Lancet Planetary Health (2024)

Focusing specifically on the gender-climate-health nexus, this Personal View builds on existing feminist works and analyses to discuss why intersectional approaches to climate policy and inclusive representation in climate decision making are crucial for achieving just and equitable solutions to address the impacts of climate change on human health and societies. This Personal View highlights how women, girls, and gender-diverse people often face disproportionate climate-related health impacts, particularly those who experience compounding and overlapping vulnerabilities due to current and former systems of oppression. We summarise the insufficient meaningful inclusion of gender, health, and their intersection in international climate governance. Despite the tendency to conflate gender equality with number-based representation, climate governance under the UNFCCC (1995-2023) remains dominated by men, with several countries projected to take over a decade to achieve gender parity in their Party delegations. Advancing gender-responsiveness in climate policy and implementation and promoting equitable participation in climate governance will not only improve the inclusivity and effectiveness of national strategies, but will also build more resilient, equitable, and healthier societies.
Letter to the Editor Clinical and Molecular Hepatology Correspondence on the Editorial regarding “The use of transient elastography for predicting hepatocellular carcinoma in chronic hepatitis B patients”
Authors: Mirko Zoncapè, Emmanuel A Tsochatzis
Journal: Clinical and Molecular Hepatology (2024)

Letter to the Editor Clinical and Molecular Hepatology Correspondence on the Editorial regarding "The use of transient elastography for predicting hepatocellular carcinoma in chronic hepatitis B patients"
Hard-to-treat autoimmune hepatitis and primary biliary cholangitis: The dawn of a new era of pharmacological treatment
Authors: Atsumasa Komori, Yuki Kugiyama
Journal: Clinical and Molecular Hepatology (2024)

Patients with hard-to-treat autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC) are defined a posteriori as those who do not show a sufficient response or are intolerant to pharmacological treatments, thus not achieving biochemical surrogate endpoints that are associated with long-term liver-related-event-free survival. The absence of a recently harmonized definition of 'complete biochemical response within 6 months (CBR≤6M)', which is defined as the normalization of serum transaminase and IgG levels below the upper limit of normal (ULN) at ≤6 months after treatment initiation is regarded as hard-to-treat AIH. The implementation of CBR≤6M, in turn, has been facilitating clinical trials, e.g., between azathioprine and mycophenolate mofetil, to reconsider appropriate first-line steroid sparing agents, leading to a reduction in the number of hard-to-treat AIH cases. Regarding PBC, one of the disseminated definitions of hard-to-treat patients is the absence of POISE criteria, which are evaluated at 12 months with serum alkaline phosphatase and bilirubin levels, after the introduction of ursodeoxycholic acid. Hard-to-treat PBC not meeting the POISE criteria has very recently been the target population for the U.S. FDA-approved second-line drugs, elafibranor and seladelpar. In future pharmacological treatment of AIH and PBC, the primary objective for AIH is likely to focus on lowering the number of hard-to-treat patients with personalized steroid sparing treatment regimens. A challenging goal in PBC treatment is the further optimization of treatment surrogate endpoints, even to the stricter ALP normalization, with which an indication of second- or later-line drugs might be expanded, but could ultimately lengthen patients' long-term survival.
Nano Plasma Membrane Vesicle‐Lipid Nanoparticle Hybrids for Enhanced Gene Delivery and Expression
Authors: Claudio Luca Alter, Claudia Lotter, Ramya Deepthi Puligilla, Jan Stephan Bolten, Jaroslaw Sedzicki, Jason Marchese, Valentin Schittny, Francesca Rucci, Michael Beverly, Cornelia G. Palivan, Pascal Detampel, Tomaž Einfalt, Jörg Huwyler
Journal: Advanced Healthcare Materials (2024)

Lipid nanoparticles (LNPs) have emerged as the leading nonviral nucleic acid (NA) delivery system, gaining widespread attention for their use in COVID-19 vaccines. They are recognized for their efficient NA encapsulation, modifiability, and scalable production. However, LNPs face efficacy and potency limitations due to suboptimal intracellular processing, with endosomal escape efficiencies (ESE) below 2.5%. Additionally, up to 70% of NPs undergo recycling and exocytosis after cellular uptake. In contrast, cell-derived vesicles offer biocompatibility and high-delivery efficacy but are challenging to load with exogenous NAs and to manufacture at large-scale. To leverage the strengths of both systems, a hybrid system is designed by combining cell-derived vesicles, such as nano plasma membrane vesicles (nPMVs), with LNPs through microfluidic mixing and subsequent dialysis. These hybrids demonstrate up to tenfold increase in ESE and an 18-fold rise in reporter gene expression in vitro and in vivo in zebrafish larvae (ZFL) and mice, compared to traditional LNPs. These improvements are linked to their unique physico-chemical properties, composition, and morphology. By incorporating cell-derived vesicles, this strategy streamlines the development process, significantly enhancing the efficacy and potency of gene delivery systems without the need for extensive screening.
Genetically determined telomere length in monoclonal gammopathy of undetermined significance, multiple myeloma risk and outcome
Authors: Matteo Giaccherini, Alyssa I Clay-Gilmour, Romano Liotti, Angelica Macauda, Manuel Gentiluomo, Elizabeth E Brown, Mitchell J Machiela, Stephen J Chanock, Michelle A T Hildebrandt, Aaron D Norman, Elisabet Manasanch, S Vincent Rajkumar, Jonathan N Hofmann, Sonja I Berndt, Parveen Bhatti, Graham G Giles, Elad Ziv, Shaji K Kumar, Nicola J Camp, Wendy Cozen, Susan L Slager, Federico Canzian, Federica Gemignani, Celine M Vachon, Daniele Campa
Journal: Blood Cancer Journal (2024)
Hepatitis E as a trigger for Acute-on-Chronic Liver Failure
Authors: Maria Buti, Juan Carlos Ruiz-Cobo, Rafael Esteban, Mar Riveiro-Barciela
Journal: Clinical and Molecular Hepatology (2024)

Acute hepatitis E virus (HEV) infection is typically self-limiting and has a favourable prognosis. However, certain populations such as patients with pre-existing chronic liver disease may experience severe manifestations, including progression to acute-on-chronic liver failure (ACLF). Among viral hepatitis types, hepatitis A, E, and B are major causes of ACLF. Active screening and early diagnosis of HEV infection in patients with cirrhosis, especially those who develop ACLF, can improve management and enable timely antiviral therapy. Preventive measures, including HEV vaccination for high-risk groups, could reduce the morbidity and mortality associated with hepatitis E.
Neuromuscular Regeneration of Volumetric Muscle Loss Injury in Response to Agrin‐Functionalized Tissue Engineered Muscle Grafts and Rehabilitative Exercise
Authors: Eszter Mihaly, Neha Chellu, Shama R. Iyer, Eileen Y. Su, Dallas E. Altamirano, Shaquielle T. Dias, Warren L. Grayson
Journal: Advanced Healthcare Materials (2024)

Neuromuscular deficits compound the loss of contractile tissue in volumetric muscle loss (VML). Two avenues for promoting recovery are neuromuscular junction (NMJ)-promoting substrates (e.g., agrin) and endurance exercise. Although mechanical stimulation enhances agrin-induced NMJ formation, the two modalities have yet to be evaluated combinatorially. It is hypothesized that the implantation of human myogenic progenitor-seeded tissue-engineered muscle grafts (hTEMGs) in combination with agrin treatment and/or exercise will enhance neuromuscular recovery after VML. The hTEMGs alone transplant into VML defects promote significant regeneration with minimal scarring. A sex-appropriate, low-intensity continuous running exercise paradigm increases acetylcholine receptor (AChR) cluster density in male mice twofold relative to hTEMG alone after 7 weeks of treadmill training (p < 0.05). To further promote neuromuscular recovery, agrin is incorporated into the scaffolds via covalent tethering. In vitro, agrin increases the proliferation of hMPs, and trends toward greater myogenic maturity and AChR clustering. Upon transplantation, both hTEMGs + agrin and hTEMGs + exercise induce near 100% recovery of muscle mass and increase twitch and tetanic force output (p > 0.05). However, agrin treatment in combination with exercise produces no additional benefit. These data highlight the unprecedented regenerative potential of using hTEMGs together with either agrin or exercise supplementation to treat VML injuries.
Actuating Extracellular Matrices Decouple the Mechanical and Biochemical Effects of Muscle Contraction on Motor Neurons
Authors: Angel Bu, Ferdows Afghah, Nicolas Castro, Maheera Bawa, Sonika Kohli, Karina Shah, Brandon Rios, Vincent Butty, Ritu Raman
Journal: Advanced Healthcare Materials (2024)

Abstract Emerging in vivo evidence suggests that repeated muscle contraction, or exercise, impacts peripheral nerves. However, the difficulty of isolating the muscle‐specific impact on motor neurons in vivo, as well as the inability to decouple the biochemical and mechanical impacts of muscle contraction in this setting, motivates investigating this phenomenon in vitro. This study demonstrates that tuning the mechanical properties of fibrin enables longitudinal culture of highly contractile skeletal muscle monolayers, enabling functional characterization of and long‐term secretome harvesting from exercised tissues. Motor neurons stimulated with exercised muscle‐secreted factors significantly upregulate neurite outgrowth and migration, with an effect size dependent on muscle contraction intensity. Actuating magnetic microparticles embedded within fibrin hydrogels enable dynamically stretching motor neurons and non‐invasively mimicking the mechanical effects of muscle contraction. Interestingly, axonogenesis is similarly upregulated in both mechanically and biochemically stimulated motor neurons, but RNA sequencing reveals different transcriptomic signatures between groups, with biochemical stimulation having a greater impact on cell signaling related to axonogenesis and synapse maturation. This study leverages actuating extracellular matrices to robustly validate a previously hypothesized role for muscle contraction in regulating motor neuron growth and maturation from the bottom‐up through both mechanical and biochemical signaling.
Impact of lenalidomide-bortezomib-dexamethasone induction on patients with newly diagnosed multiple myeloma and renal impairment: Results from the Connect® MM Registry
Authors: Sikander Ailawadhi, Hans C. Lee, James Omel, Kathleen Toomey, James W. Hardin, Cristina J. Gasparetto, Sundar Jagannath, Robert M. Rifkin, Brian G. M. Durie, Mohit Narang, Howard R. Terebelo, Prashant Joshi, Ying-Ming Jou, Jorge Mouro, Edward Yu, Rafat Abonour
Journal: Blood Cancer Journal (2024)

Limited data exist on the effects of induction treatment in patients with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI), who may also be ineligible for autologous stem cell transplant. This analysis investigated the impact of lenalidomide-bortezomib-dexamethasone (RVd) induction on renal function in patients from the Connect® MM Registry based on transplant status. Eligible patients were aged ≥18 years with symptomatic MM diagnosed ≤2 months before enrollment. Patients in this analysis received front-line RVd for ≥3 cycles and were grouped by transplant status and baseline renal function. As of August 4, 2021, 344 transplanted and 289 non-transplanted patients had received RVd for ≥3 cycles at induction. Improved renal function was observed at 3, 6, and 12 months in patients with all severities of RI at baseline. In patients with >60 and ≤60 creatinine clearance mL/min at baseline, median progression-free survival was 49.4 months and 47.6 months in transplanted patients and 35.7 months and 29.1 months in non-transplanted patients, respectively. These results provide real-world evidence that patients with NDMM and RI who receive front-line RVd for ≥3 cycles may have improved renal function regardless of transplant status, with renal function no longer affecting the long-term outcome. Clinical trial information: NCT01081028.
A simplified, two-factor clinical prognostic scoring system for patients with newly diagnosed Hodgkins Lymphoma
Authors: Charanpreet Singh, Lekshmon Ks, Arihant Jain, Deepesh Lad, Alka Khadwal, Rajender Basher, Amanjit Bal, Radhika Srinivasan, Subhash Varma, Pankaj Malhotra, Gaurav Prakash
Journal: Blood Cancer Journal (2024)
SpottedPy quantifies relationships between spatial transcriptomic hotspots and uncovers environmental cues of epithelial-mesenchymal plasticity in breast cancer
Authors: Eloise Withnell, Maria Secrier
Journal: Genome biology (2024)

Spatial transcriptomics is revolutionizing the exploration of intratissue heterogeneity in cancer, yet capturing cellular niches and their spatial relationships remains challenging. We introduce SpottedPy, a Python package designed to identify tumor hotspots and map spatial interactions within the cancer ecosystem. Using SpottedPy, we examine epithelial-mesenchymal plasticity in breast cancer and highlight stable niches associated with angiogenic and hypoxic regions, shielded by CAFs and macrophages. Hybrid and mesenchymal hotspot distribution follows transformation gradients reflecting progressive immunosuppression. Our method offers flexibility to explore spatial relationships at different scales, from immediate neighbors to broader tissue modules, providing new insights into tumor microenvironment dynamics.