tbuckley/cabot-search huggingface dataset:
Fecal Urgency in Ulcerative Colitis: Impact on Quality of Life and Psychological Well-Being in Active and Inactive Disease States
Authors: Gaurav B. Nigam, Jimmy K. Limdi, Sebastian Bate, Shaheen Hamdy, Dipesh H. Vasant
Journal: Clinical Gastroenterology and Hepatology (2023)

Ulcerative colitis (UC) is a chronic, relapsing-and-remitting, potentially progressive form of inflammatory bowel disease (IBD) with multidimensional and often negative effects on patients' lives. Fecal urgency, the sudden and compelling desire to defecate, often accompanied by impaired bowel control leading to frequent and urgent trips to the bathroom, is a distressing symptom, experienced by more than 50% of patients with UC.
Olfactory immune response to SARS-CoV-2
Authors: Sebastian A. Wellford, E. Ashley Moseman
Journal: Cellular and Molecular Immunology (2023)

Abstract Numerous pathogens can infect the olfactory tract, yet the pandemic caused by SARS-CoV-2 has strongly emphasized the importance of the olfactory mucosa as an immune barrier. Situated in the nasal passages, the olfactory mucosa is directly exposed to the environment to sense airborne odorants; however, this also means it can serve as a direct route of entry from the outside world into the brain. As a result, olfactotropic infections can have serious consequences, including dysfunction of the olfactory system, CNS invasion, dissemination to the lower respiratory tract, and transmission between individuals. Recent research has shown that a distinctive immune response is needed to protect this neuronal and mucosal tissue. A better understanding of innate, adaptive, and structural immune barriers in the olfactory mucosa is needed to develop effective therapeutics and vaccines against olfactotropic microbes such as SARS-CoV-2. Here, we summarize the ramifications of SARS-CoV-2 infection of the olfactory mucosa, review the subsequent immune response, and discuss important areas of future research for olfactory immunity to infectious disease.
CXCR4‐Expressing Mesenchymal Stem Cells Derived Nanovesicles for Rheumatoid Arthritis Treatment
Authors: Jingjing Gan, Xiaoxuan Zhang, Guangcai Chen, Xubin Hao, Yuanjin Zhao, Lingyun Sun
Journal: Advanced Healthcare Materials (2023)

Cell membrane camouflage technology, which a demonstrated value for the bionic replication of natural cell membrane properties, is an active area of ongoing research readily applicable to nanomedicine. How to realize immune evasion, slow down the clearance from the body, and improve targeting are still worth great efforts for this technology. Herein, novel cell membrane-mimicked nanovesicles from genetically engineered mesenchymal stem cells (MSCs) are presented as a potential anti-inflammatory platform for rheumatoid arthritis (RA) management. Utilizing the synthetic biology approach, the biomimetic nanoparticles are constructed by fusing C-X-C motif chemokine receptor4 (CXCR4)-anchored MSC membranes onto drug-loaded polymeric cores (MCPNs), which make them ideal decoys of stromal cell-derived factor-1 (SDF-1)-targeted arthritis. These resulting nanocomplexes function to escape from the immune system and enhance accumulation in the established inflamed joints via the CXCR4/SDF-1 chemotactic signal axis, thereby achieving an affinity to activated macrophages and synovial fibroblasts. It is further demonstrated that the MCPNs can significantly suppress synovial inflammation and relieve pathological conditions with favorable safety properties in collagen-induced arthritis mice. These findings indicate the clinical value of MCPNs as biomimetic nanodrugs for RA therapy and related diseases.
Granular Hydrogels for Harnessing the Immune Response
Authors: Adrienne E. Widener, Abilene Roberts, Edward A. Phelps
Journal: Advanced Healthcare Materials (2023)

This review aims to understand the current progress in immune-instructive granular hydrogels and identify the key features used as immunomodulatory strategies. Published work is systematically reviewed and relevant information about granular hydrogels used throughout these studies is collected. The base polymer, microgel generation technique, polymer crosslinking chemistry, particle size and shape, annealing strategy, granular hydrogel stiffness, pore size and void space, degradability, biomolecule presentation, and drug release are cataloged for each work. Several granular hydrogel parameters used for immune modulation: porosity, architecture, bioactivity, drug release, cell delivery, and modularity, are identified. The authors found in this review that porosity is the most significant factor influencing the innate immune response to granular hydrogels, while incorporated bioactivity is more significant in influencing adaptive immune responses. Here, the authors' findings and summarized results from each section are presented and suggestions are made for future studies to better understand the benefits of using immune-instructive granular hydrogels.
Gender-affirming hormone therapy in Portugal: knowledge, safety and adherence
Authors: Rafael Baptista Santos, Carolina Lemos, Miguel Saraiva
Journal: International Journal of Transgender Health (2023)

Background: More research is needed to understand the knowledge, experiences, safety, and adherence of individuals on gender-affirming hormone therapy (GAHT) for gender dysphoria treatment. Aim: To assess the knowledge of the Portuguese transgender population on GAHT about the therapy, examine the experiences of those who initiated it through the Portuguese National Health System, and evaluate the safety, monitoring and adherence to hormonal therapy. Methods: Cross-sectional study with Portuguese transgender adults who had hormonal therapy. Participants completed an original questionnaire that utilized an ordinal Likert-style scale that ranged from 0 (worst result) to 6 (best result) for most items. Descriptive statistics and non-parametric tests were used to analyze both categorical and continuous variables. The level of statistical significance was set at 0.05. Results: Participants' knowledge on GAHT was rated with a median of 5 points, relying mostly on the internet for information. 14.1% felt insufficiently informed. 71.2% faced obstacles obtaining GAHT, with long waiting times being the most common. Feminizing therapy was significantly more expensive. Initial consultation was often with psychologists/sexologists, with endocrinologists commonly being the first providers of GAHT. 43.3% didn't undergo informed consent and 11.3% had no pretreatment blood tests. Only 53.2% discussed fertility with medical professionals, and of those, only 8.0% opted for it. 79.6% regularly underwent routine analyses and 87.3% were followed up in medical appointments, mainly with an endocrinologist. 6.3% of participants discontinued therapy, mostly due to adverse effects and difficulty obtaining prescriptions. Discussion: Internet sources dominated as the main information channel for GAHT, emphasizing the importance of healthcare professionals guiding patients to reliable sources. Limited healthcare provider knowledge and access barriers were identified. Primary care physicians had limited involvement, raising safety concerns. Inadequate fertility counseling and follow-up in family medicine were found. Discontinuation of therapy and nonadherence highlighted the need for comprehensive care and monitoring.
Principles for the Physician-Led Patient-Centered Medical Home and Other Approaches to Team-Based Care: A Position Paper From the American College of Physicians
Authors: Ryan Crowley, David Pugach, Margo Williams, Jason Goldman, David Hilden, Anne Furey Schultz, Micah Beachy, David Hilden, Micah Beachy, Jan K. Carney, Haidn Foster, Austin Hoeg, Matthew Hollon, Cynthia A. Jumper, Selvam Joseph Mascarenhas, Ankita Sagar, Jenny R. Silberger, Jamar Slocum, Michael Tan, Elham A. Yousef, Jason M. Goldman, Anne Furey Schultz, Leslie F. Algase, Felicia Austin-Jordan, Sarah G. Candler, Robert B. Hauger, Stuart I. Henochowicz, Ali M. Khan, Scott Manaker, Kristin Mitchell, Neha Chiruvolu Singh, Earl Stewart
Journal: Annals of Internal Medicine (2023)

Team-based care models such as the Patient-Centered Medical Home are associated with improved patient health outcomes, better team coordination and collaboration, and increased well-being among health care professionals. Despite these attributes, hindrances to wider adoption remain. In addition, some health care professionals have sought to practice independent of the physician-led health care team, potentially undermining patient access to physicians who have the skills and training to deliver whole-person, comprehensive, and longitudinal care. In this paper, the American College of Physicians reaffirms the importance of the physician-led health care team and offers policy recommendations on professionalism, payment models, training, licensure, and research to support the expansion of dynamic clinical care teams.
Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040
Authors: A.B. El-Khoueiry, J. Trojan, T. Meyer, T. Yau, I. Melero, M. Kudo, C. Hsu, T.-Y. Kim, S.-P. Choo, Y.-K. Kang, W. Yeo, A. Chopra, S. Soleymani, J. Yao, J. Neely, M. Tschaika, T.H. Welling, B. Sangro
Journal: Annals of Oncology (2023)

Background Patients with advanced hepatocellular carcinoma (aHCC) have a poor prognosis and high mortality. Nivolumab monotherapy demonstrated clinical benefit with an acceptable safety profile in patients with aHCC in the CheckMate 040 study. Five-year follow-up of the sorafenib-naive and sorafenib-experienced cohorts of CheckMate 040 are presented here. Patients and methods Patients received nivolumab monotherapy at dose levels of 0.1-10.0 mg/kg (dose-escalation phase) or 3 mg/kg (dose-expansion phase) every 2 weeks until disease progression or unacceptable toxicity. Primary endpoints were safety and tolerability (dose escalation), and objective response rate (ORR) by blinded independent central review (BICR) and by investigator per RECIST version 1.1 (dose expansion). Results Eighty sorafenib-naive and 154 sorafenib-experienced patients were treated. Minimum follow-up in both groups was 60 months. ORR per BICR was 20% (95% CI 12-30) and 14% (95% CI 9-21) in the sorafenib-naive and sorafenib-experienced groups, respectively. Responses occurred regardless of HCC etiology or baseline tumor cell programmed death ligand 1 (PD-L1) expression levels. Median overall survival (OS) was 26.6 months (95% CI 16.6-30.6) and 15.1 months (95% CI 13.0-18.2) in sorafenib-naive and sorafenib-experienced patients, respectively. The 3-year OS rates were 28% in the sorafenib-naive and 20% in the sorafenib-experienced group; 5-year OS rates were 14% and 12%, respectively. No new safety signals were identified; grade 3/4 treatment-related adverse events were observed in 33% and 21% in the sorafenib-naive and sorafenib-experienced patients, respectively. Biomarker analyses showed that baseline PD-L1 expression ≥1% was associated with higher ORR and longer OS compared with PD-L1 <1%. In the sorafenib-naive group, patients with OS ≥3 years exhibited higher baseline CD8 T-cell density compared with those with OS <1 year. Conclusion With 5 years of follow-up, nivolumab monotherapy continued to provide durable clinical benefit with manageable safety in sorafenib-naive and sorafenib-experienced patients with aHCC.
Early detection of interstitial lung disease in rheumatic diseases: A joint statement from the Portuguese Pulmonology Society, the Portuguese Rheumatology Society, and the Portuguese Radiology and Nuclear Medicine Society
Authors: A. Morais, A.C. Duarte, M.O. Fernandes, A. Borba, C. Ruano, I.D. Marques, J. Calha, J.C. Branco, J.M. Pereira, M.J. Salvador, M. Bernardes, N. Khmelinskii, P. Pinto, R Pinto-Basto, S. Freitas, S. Campainha, T. Alfaro, A. Cordeiro
Journal: Pulmonology (2023)

Interstitial lung disease (ILD) contributes significantly to morbidity and mortality in connective tissue disease (CTD). Early detection and accurate diagnosis are essential for informing treatment decisions and prognosis in this setting. Clear guidance on CTD-ILD screening, however, is lacking. To establish recommendations for CTD-ILD screening based on the current evidence. Following an extensive literature research and evaluation of articles selected for their recency and relevance to the characterization, screening, and management of CTD-ILD, an expert panel formed by six pulmonologists from the Portuguese Society of Pulmonology, six rheumatologists from the Portuguese Society of Rheumatology, and six radiologists from the Portuguese Society of Radiology and Nuclear Medicine participated in a multidisciplinary discussion to produce a joint statement on screening recommendations for ILD in CTD. The expert panel achieved consensus on when and how to screen for ILD in patients with systemic sclerosis, rheumatoid arthritis, mixed connective tissue disease, Sjögren syndrome, idiopathic inflammatory myopathies and systemic lupus erythematous. Despite the lack of data on screening for CTD-ILD, an expert panel of pulmonologists, rheumatologists and radiologists agreed on a series of screening recommendations to support decision-making and enable early diagnosis of ILD to ultimately improve outcomes and prognosis in patients with CTD.
Rewiring chaperone-mediated autophagy in cancer by a prion-like chemical inducer of proximity to counteract adaptive immune resistance
Authors: Jin Yan, Dan Liu, Jingmei Wang, Weiming You, Wenguang Yang, Siqi Yan, Wangxiao He
Journal: Drug Resistance Updates (2023)

Chaperone-mediated autophagy (CMA), a proteolytic system contributing to the degradation of intracellular proteins in lysosomes, is upregulated in tumors for pro-tumorigenic and pro-survival purposes. In this study, bioinformatics analysis revealed the co-occurrence of upregulated CMA and PD-L1 accumulation in metastatic melanoma with adaptive immune resistance (AIR) to anti-PD1 treatment, suggesting the potential therapeutic effects of rewiring CMA for PD-L1 degradation. Furthermore, this co-occurrence is attributed to IFN-γ-mediated compensatory up-regulation of PD-L1 and CMA, accompanied by enhanced macropinocytosis. Drawing inspiration from the cellular uptake of prions via macropinocytosis, a prion-like chemical inducer of proximity called SAP was engineered using self-assembly of the designed chiral peptide PHA. By exploiting sensitized macropinocytosis, SAP clandestinely infiltrates tumor cells and subsequently disintegrates into PHA, which reprograms CMA by inducing PD-L1 close to HSPA8. SAP degrades PD-L1 in a CMA-dependent manner and effectively restores the anti-tumor immune response in both allografting and Hu-PDX melanoma mouse models with AIR while upholding a high safety profile. Collectively, the reported SAP not only presents an immune reactivation strategy with clinical translational potential for overcoming AIR in cutaneous melanomas but serves as a reproducible example of precision-medicine-guided drug development that fully leverages specific cellular indications in pathological states.
Antiviral potency of long-acting islatravir subdermal implant in SHIV-infected macaques
Authors: Fernanda P. Pons-Faudoa, Nicola Di Trani, Simone Capuani, Ilaria Facchi, Anthony M. Wood, Bharti Nehete, Ashley DeLise, Suman Sharma, Kathryn A. Shelton, Lane R. Bushman, Corrine Ying Xuan Chua, Michael M. Ittmann, Jason T. Kimata, Peter L. Anderson, Pramod N. Nehete, Roberto C. Arduino, Alessandro Grattoni
Journal: Journal of Controlled Release (2023)

Treatment nonadherence is a pressing issue in people living with HIV (PLWH), as they require lifelong therapy to maintain viral suppression. Poor adherence leads to antiretroviral (ARV) resistance, transmission to others, AIDS progression, and increased morbidity and mortality. Long-acting (LA) ARV therapy is a promising strategy to combat the clinical drawback of user-dependent dosing. Islatravir (ISL) is a promising candidate for HIV treatment given its long half-life and high potency. Here we show constant ISL release from a subdermal LA nanofluidic implant achieves viral load reduction in SHIV-infected macaques. Specifically, a mean delivery dosage of 0.21 ± 0.07 mg/kg/day yielded a mean viral load reduction of -2.30 ± 0.53 log
Recent strategies for evoking immunogenic Pyroptosis in antitumor immunotherapy
Authors: Zhangxin He, Dexiang Feng, Chaoji Zhang, Zhiqian Chen, He Wang, Jianquan Hou, Shengliang Li, Xuedong Wei
Journal: Journal of Controlled Release (2024)

Pyroptosis is a specific type of programmed cell death (PCD) characterized by distinct morphological changes, including cell swelling, membrane blebbing, DNA fragmentation, and eventual cell lysis. Pyroptosis is closely associated with human-related diseases, such as inflammation and malignancies. Since the initial observation of pyroptosis in Shigella flexneri-infected macrophages more than 20 years ago, various pyroptosis-inducing agents, including ions, small molecules, and biological nanomaterials, have been developed for tumor treatment. Given that pyroptosis can activate the body's robust immune response against tumor and promote the formation of the body's long-term immune memory in tumor treatment, its status as a type of immunogenic cell death is self-evident. Therefore, pyroptosis should be used as a powerful anti-tumor strategy. However, there still is a lack of a comprehensive summary of the most recent advances in pyroptosis-based cancer therapy. Therefore, it is vital to fill this gap and inspire future drug design to better induce tumor cells to undergo pyroptosis to achieve advanced anti-tumor effects. In this review, we summarize in detail the most recent advances in triggering tumor cell immunogenic pyroptosis for adequate tumor clearance based on various treatment modalities, and highlight material design and therapeutic advantages. Besides, we also provide an outlook on the prospects of this emerging field in the next development.
Overcoming the Dilemma of In Vivo Stable Adhesion and Sustained Degradation by the Molecular Design of Polyurethane Adhesives for Bone Fracture Repair
Authors: Qiang Li, Bo Tang, Xinchang Liu, Buyun Chen, Xinling Wang, Haijun Xiao, Zhen Zheng
Journal: Advanced Healthcare Materials (2023)

Abstract Bone adhesive is a promising candidate to revolutionize the clinical treatment of bone repairs. However, several drawbacks have limited its further clinical application, such as unreliable wet adhesive performance leading to fixation failure and poor biodegradability inhibiting bone tissue growth. By incorporating catechol groups and disulfide bonds into polyurethane (PU) molecules, an injectable and porous PU adhesive is developed with both superior wet adhesion and biodegradability to facilitate the reduction and fixation of comminuted fractures and the subsequent regeneration of bone tissue. The bone adhesive can be cured within a reasonable time acceptable to a surgeon, and then the wet bone adhesive strength is near 1.30 MPa in 1 h. Finally, the wet adhesive strength to the cortical bone will achieve about 1.70 MPa, which is also five times more than nonresorbable poly(methyl methacrylate) bone cement. Besides, the cell culture experiments also indicate that the adhesives show excellent biocompatibility and osteogenic ability in vitro. Especially, it can degrade in vivo gradually and promote fracture healing in the rabbit iliac fracture model. These results demonstrate that this ingenious bone adhesive exhibits great potential in the treatment of comminuted fractures, providing fresh insights into the development of clinically applicable bone adhesives.
Determinants of Impaired Peak Oxygen Uptake in Breast Cancer Survivors: JACC: CardioOncology Primer
Authors: Stephen J. Foulkes, Mark J. Haykowsky, Todd Li, Jing Wang, Megan Kennedy, Amy A. Kirkham, Richard B. Thompson, D. Ian Paterson, Andre La Gerche, Edith Pituskin
Journal: JACC CardioOncology (2023)

• Exercise intolerance is common among breast cancer survivors. • Exercise intolerance in breast cancer survivors is related to cardiac, vascular, and skeletal muscle impairments. • Holistic rehabilitation or pharmacological therapies are needed to address these impairments.
Comparison of OLGA and OLGIM as predictors of gastric cancer in a Latin American population: the ECHOS Study
Authors: Gonzalo Latorre, Felipe Silva, Isabella Montero, Miguel Bustamante, Eitan Dukes, Javier Uribe, Oscar Corsi Sotelo, Diego Reyes, Eduardo Fuentes-López, Margarita Pizarro, Patricio Medel, Javiera Torres, Juan Carlos Roa, Sebastián Pizarro, Pablo Achurra, Andrés Donoso, Ignacio Wichmann, Alejandro H Corvalán, Javier Chahuan, Roberto Candia, Carlos Agüero, Robinson Gonzalez, Jose Ignacio Vargas, Alberto Espino, M Constanza Camargo, Shailja C Shah, Arnoldo Riquelme
Journal: Gut (2023)
Elevated ferritin, mediated by IL-18 is associated with systemic inflammation and mortality in acute respiratory distress syndrome (ARDS)
Authors: Puja Mehta, Romit J Samanta, Katherine Wick, Rebecca C Coll, Thea Mawhinney, Patrick G McAleavey, Andrew J Boyle, John Conlon, Manu Shankar-Hari, Angela Rogers, Carolyn S Calfee, Michael A Matthay, Charlotte Summers, Rachel Clare Chambers, Daniel Francis McAuley, Cecilia M O'Kane
Journal: Thorax (2023)

Background Inflammatory subphenotypes have been identified in acute respiratory distress syndrome (ARDS). Hyperferritinaemia in sepsis is associated with hyperinflammation, worse clinical outcomes, and may predict benefit with immunomodulation. Our aim was to determine if raised ferritin identified a subphenotype in patients with ARDS. Methods Baseline plasma ferritin concentrations were measured in patients with ARDS from two randomised controlled trials of simvastatin (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction-2 (HARP-2); discovery cohort, UK) and neuromuscular blockade (ROSE; validation cohort, USA). Results were analysed using a logistic regression model with restricted cubic splines, to determine the ferritin threshold associated with 28-day mortality. Results Ferritin was measured in 511 patients from HARP-2 (95% of patients enrolled) and 847 patients (84% of patients enrolled) from ROSE. Ferritin was consistently associated with 28-day mortality in both studies and following a meta-analysis, a log-fold increase in ferritin was associated with an OR 1.71 (95% CI 1.01 to 2.90) for 28-day mortality. Patients with ferritin &gt;1380 ng/mL (HARP-2 28%, ROSE 24%) had a significantly higher 28-day mortality and fewer ventilator-free days in both studies. Mediation analysis, including confounders (acute physiology and chronic health evaluation-II score and ARDS aetiology) demonstrated a statistically significant contribution of interleukin (IL)-18 as an intermediate pathway between ferritin and mortality. Conclusions Ferritin is a clinically useful biomarker in ARDS and is associated with worse patient outcomes. These results provide support for prospective interventional trials of immunomodulatory agents targeting IL-18 in this hyperferritinaemic subgroup of patients with ARDS.