tbuckley/cabot-search huggingface dataset:
Reply to Richard J. Wassersug, Paul F. Schellhammer, and Erik Wibowo’s Letter to the Editor re: Christoper J. Logothetis, Andrew W. Hahn. Challenging the Prevailing Therapeutic Dogma for Prostate Cancer: The Case for an Overlap Syndrome. Eur Urol 2024;85:3–7
Authors: Christopher J. Logothetis, Andrew W. Hahn
Journal: European Urology (2024)
Estimating the burden of vitiligo: a systematic review and modelling study
Authors: Jennifer Akl, Solam Lee, Hyun Jeong Ju, Rosa Parisi, Ji Yoon Kim, Jae Joon Jeon, Yeon-Woo Heo, Viktoria Eleftheriadou, Iltefat Hamzavi, Christopher E M Griffiths, Darren M Ashcroft, Venkataram Mysore, Somesh Gupta, Davinder Parsad, Henry Lim, Jung Min Bae, Khaled Ezzedine
Journal: The Lancet Public Health (2024)

Vitiligo is a chronic autoimmune disease characterised by depigmented skin patches, which can pose substantial psychosocial challenges particularly in individuals with dark skin tones. Despite its impact on quality of life, there is an absence of standardised global epidemiological data. We sought to address this gap with the present study.
Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting
Authors: Mitra K. Nadim, John A. Kellum, Lui Forni, Claire Francoz, Sumeet K. Asrani, Marlies Ostermann, Andrew S. Allegretti, Javier A. Neyra, Jody C. Olson, Salvatore Piano, Lisa B. VanWagner, Elizabeth C. Verna, Ayse Akcan-Arikan, Paolo Angeli, Justin M. Belcher, Scott W. Biggins, Akash Deep, Guadalupe Garcia-Tsao, Yuri S. Genyk, Pere Gines, Patrick S. Kamath, Sandra L. Kane-Gill, Manish Kaushik, Nuttha Lumlertgul, Etienne Macedo, Rakhi Maiwall, Sebastian Marciano, Raimund H. Pichler, Claudio Ronco, Puneeta Tandon, Juan-Carlos Q. Velez, Ravindra L. Mehta, François Durand
Journal: Journal of Hepatology (2024)

Patients with cirrhosis are prone to develop acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.
ALT to qHBsAg ratio predicts long-term HBsAg seroclearance after entecavir cessation in Chinese patients with chronic hepatitis B
Authors: Ryan Hin-Man Leung, Rex Wan-Hin Hui, Lung-Yi Mak, Xianhua Mao, Kevin Sze-Hang Liu, Danny Ka-Ho Wong, James Fung, Wai-Kay Seto, Man-Fung Yuen
Journal: Journal of Hepatology (2024)
Sensorless volumetric reconstruction of fetal brain freehand ultrasound scans with deep implicit representation
Authors: Pak-Hei Yeung, Linde S. Hesse, Moska Aliasi, Monique C. Haak, Weidi Xie, Ana I.L. Namburete
Journal: Medical Image Analysis (2024)

Three-dimensional (3D) ultrasound imaging has contributed to our understanding of fetal developmental processes by providing rich contextual information of the inherently 3D anatomies. However, its use is limited in clinical settings, due to the high purchasing costs and limited diagnostic practicality. Freehand 2D ultrasound imaging, in contrast, is routinely used in standard obstetric exams, but inherently lacks a 3D representation of the anatomies, which limits its potential for more advanced assessment. Such full representations are challenging to recover even with external tracking devices due to internal fetal movement which is independent from the operator-led trajectory of the probe. Capitalizing on the flexibility offered by freehand 2D ultrasound acquisition, we propose ImplicitVol to reconstruct 3D volumes from non-sensor-tracked 2D ultrasound sweeps. Conventionally, reconstructions are performed on a discrete voxel grid. We, however, employ a deep neural network to represent, for the first time, the reconstructed volume as an implicit function. Specifically, ImplicitVol takes a set of 2D images as input, predicts their locations in 3D space, jointly refines the inferred locations, and learns a full volumetric reconstruction. When testing natively-acquired and volume-sampled 2D ultrasound video sequences collected from different manufacturers, the 3D volumes reconstructed by ImplicitVol show significantly better visual and semantic quality than the existing interpolation-based reconstruction approaches. The inherent continuity of implicit representation also enables ImplicitVol to reconstruct the volume to arbitrarily high resolutions. As formulated, ImplicitVol has the potential to integrate seamlessly into the clinical workflow, while providing richer information for diagnosis and evaluation of the developing brain.
Advances in molecular targeted drugs in combination with CAR-T cell therapy for hematologic malignancies
Authors: Yuxian Huang, Yinjie Qin, Yingzhi He, Dezhi Qiu, Yeqin Zheng, Jiayue Wei, Lenghe Zhang, Dong‑Hua Yang, Yuhua Li
Journal: Drug Resistance Updates (2024)

Molecular targeted drugs and chimeric antigen receptor (CAR) T cell therapy represent specific biological treatments that have significantly improved the efficacy of treating hematologic malignancies. However, they face challenges such as drug resistance and recurrence after treatment. Combining molecular targeted drugs and CAR-T cells could regulate immunity, improve tumor microenvironment (TME), promote cell apoptosis, and enhance sensitivity to tumor cell killing. This approach might provide a dual coordinated attack on cancer cells, effectively eliminating minimal residual disease and overcoming therapy resistance. Moreover, molecular targeted drugs can directly or indirectly enhance the anti-tumor effect of CAR-T cells by inducing tumor target antigen expression, reversing CAR-T cell exhaustion, and reducing CAR-T cell associated toxic side effects. Therefore, combining molecular targeted drugs with CAR-T cells is a promising and novel tactic for treating hematologic malignancies. In this review article, we focus on analyzing the mechanism of therapy resistance and its reversal of CAR-T cell therapy resistance, as well as the synergistic mechanism, safety, and future challenges in CAR-T cell therapy in combination with molecular targeted drugs. We aim to explore the benefits of this combination therapy for patients with hematologic malignancies and provide a rationale for subsequent clinical studies.
How can trial designs better serve the needs of children and young people with juvenile idiopathic arthritis?
Authors: Freya Luling Feilding, Laura Crosby, Emily Earle, Richard Beesley, Kerry Leslie, Eilean MacDonald, Catherine Wright, Debbie Wilson, Anna Sherriffs, Teresa Duerr, Athimalaipet V Ramanan
Journal: The Lancet Rheumatology (2024)
Effects of levothyroxine in subclinical hypothyroidism and heart failure with reduced ejection fraction: An open-label randomized trial
Authors: Wenyao Wang, Xuan Zhang, Jun Gao, Xiangbin Meng, Jingjia Wang, Kuo Zhang, Jing Chen, Jiating Qi, Chunli Shao, Yi-Da Tang
Journal: Cell Reports Medicine (2024)

We report a randomized, multicenter, open-label trial (ClinicalTrials.gov: NCT03096613) to investigate the clinical benefits of levothyroxine (L-T4) administration in subclinical hypothyroidism (SCH) patients with heart failure with reduced ejection fraction (HFrEF). Overall, 117 patients were enrolled and received L-T4 plus standard HFrEF treatment (experimental group, N = 57) or standard HFrEF therapy alone (control group, N = 60). The change of 6-min walk test distance in the experimental group was significantly higher than that in the control group at 24 weeks (70.08 ± 85.76 m vs. 27.73 ± 82.00 m, mean difference [95% confidence interval (CI)] 46.90 [12.90, 80.90], p < 0.001). Improvements in New York Heart Association (NYHA) classification (p = 0.033) and thyroid function were significant. Adverse event incidence was similar between groups (risk ratio [95% CI]: 0.942 1.053 (0.424, 2.616); p = 0.628). L-T4 addition to HFrEF treatment improved activity tolerance, NYHA class, and thyroid function within 6 months, suggesting its potential for combined therapy in HFrEF patients with SCH. Future double-blind, placebo-controlled trials should be performed to confirm these results.
Extracellular vesicles derived from dendritic cells loaded with VEGF-A siRNA and doxorubicin reduce glioma angiogenesis in vitro
Authors: Parisa Shamshiripour, Mehrana Rahnama, Mehdi Nikoobakht, Vahideh Farzam Rad, Ali-Reza Moradi, Davoud Ahmadvand
Journal: Journal of Controlled Release (2024)
Poly(D,l-lactide-co-glycolide) particles are metabolised by the gut microbiome and elevate short chain fatty acids
Authors: Laura E. McCoubrey, Fabiana Ferraro, Nidhi Seegobin, Jérémy Verin, Haya A. Alfassam, Atheer Awad, Massimo Marzorati, Lynn Verstrepen, Jonas Ghyselinck, Julie De Munck, Jelle De Medts, Evi Steppe, Valerie De Vleeschhauwer, Gilles De Rocker, Alexandra Droesbeke, Melanie De Rijck, Sara Vanthoor, Frédéric Moens, Juergen Siepmann, Florence Siepmann, Simon Gaisford, Mine Orlu, Abdul W. Basit
Journal: Journal of Controlled Release (2024)

The production of short chain fatty acids (SCFAs) by the colonic microbiome has numerous benefits for human health, including maintenance of epithelial barrier function, suppression of colitis, and protection against carcinogenesis. Despite the therapeutic potential, there is currently no optimal approach for elevating the colonic microbiome's synthesis of SCFAs. In this study, poly(D,l-lactide-co-glycolide) (PLGA) was investigated for this application, as it was hypothesised that the colonic microbiota would metabolise PLGA to its lactate monomers, which would promote the resident microbiota's synthesis of SCFAs. Two grades of spray dried PLGA, alongside a lactate bolus control, were screened in an advanced model of the human colon, known as the M-SHIME® system. Whilst the high molecular weight (Mw) grade of PLGA was stable in the presence of the microbiota sourced from three healthy humans, the low Mw PLGA (PLGA 2) was found to be metabolised. This microbial degradation led to sustained release of lactate over 48 h and increased concentrations of the SCFAs propionate and butyrate. Further, microbial synthesis of harmful ammonium was significantly reduced compared to untreated controls. Interestingly, both types of PLGA were found to influence the composition of the luminal and mucosal microbiota in a donor-specific manner. An in vitro model of an inflamed colonic epithelium also showed the polymer to affect the expression of pro- and anti-inflammatory markers, such as interleukins 8 and 10. The findings of this study reveal PLGA's sensitivity to enzymatic metabolism in the gut, which could be harnessed for therapeutic elevation of colonic SCFAs.
Impact of conjugation to different lipids on the lymphatic uptake and biodistribution of brush PEG polymers
Authors: Mohammad Abdallah, Lihuan Lin, Ian K. Styles, Alexander Mörsdorf, James L. Grace, Gracia Gracia, Cornelia B. Landersdorfer, Cameron J. Nowell, John F. Quinn, Michael R. Whittaker, Natalie L. Trevaskis
Journal: Journal of Controlled Release (2024)

Delivery to peripheral lymphatics can be achieved following interstitial administration of nano-sized delivery systems (nanoparticles, liposomes, dendrimers etc) or molecules that hitchhike on endogenous nano-sized carriers (such as albumin). The published work concerning the hitchhiking approach has mostly focussed on the lymphatic uptake of vaccines conjugated directly to albumin binding moieties (ABMs such as lipids, Evans blue dye derivatives or peptides) and their subsequent trafficking into draining lymph nodes. The mechanisms underpinning access and transport of these constructs into lymph fluid, including potential interaction with other endogenous nanocarriers such as lipoproteins, have largely been ignored. Recently, we described a series of brush polyethylene glycol (PEG) polymers containing end terminal short-chain or medium-chain hydrocarbon tails (1C2 or 1C12, respectively), cholesterol moiety (Cho), or medium-chain or long-chain diacylglycerols (2C12 or 2C18, respectively). We evaluated the association of these materials with albumin and lipoprotein in rat plasma, and their intravenous (IV) and subcutaneous (SC) pharmacokinetic profiles. Here we fully detail the association of this suite of polymers with albumin and lipoproteins in rat lymph, which is expected to facilitate lymph transport of the materials from the SC injection site. Additionally, we characterise the thoracic lymph uptake, tissue and lymph node biodistribution of the lipidated brush PEG polymers following SC administration to thoracic lymph cannulated rats. All polymers had moderate lymphatic uptake in rats following SC dosing with the lymph uptake higher for 1C2-PEG, 2C12-PEG and 2C18-PEG (5.8%, 5.9% and 6.7% dose in lymph, respectively) compared with 1C12-PEG and Cho-PEG (both 1.5% dose in lymph). The enhanced lymph uptake of 1C2-PEG, 2C12-PEG and 2C18-PEG appeared related to their association profile with different lipoproteins. The five polymers displayed different biodistribution patterns in major organs and tissues in mice. All polymers reached immune cells deep within the inguinal lymph nodes of mice following SC dosing. The ability to access these immune cells suggests the potential of the polymers as platforms for the delivery of vaccines and immunotherapies. Future studies will focus on evaluating the lymphatic targeting and therapeutic potential of drug or vaccine-loaded polymers in pre-clinical disease models.
Piezo1 channels restrain ILC2s and regulate the development of airway hyperreactivity
Authors: Benjamin P. Hurrell, Stephen Shen, Xin Li, Yoshihiro Sakano, Mohammad Hossein Kazemi, Christine Quach, Pedram Shafiei-Jahani, Kei Sakano, Homayon Ghiasi, Omid Akbari
Journal: The Journal of Experimental Medicine (2024)

Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response in highly mechanical organs. Here, we report that Piezo1 channels repress group 2 innate lymphoid cell (ILC2)–driven type 2 inflammation in the lungs. Piezo1 is induced on lung ILC2s upon activation, as genetic ablation of Piezo1 in ILC2s increases their function and exacerbates the development of airway hyperreactivity (AHR). Conversely, Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation. Mechanistically, Yoda1 inhibits ILC2 cytokine secretion and proliferation in a KLF2-dependent manner, as we found that Piezo1 engagement reduces ILC2 oxidative metabolism. Consequently, in vivo Yoda1 treatment reduces the development of AHR in experimental models of ILC2-driven allergic asthma. Human-circulating ILC2s express and induce Piezo1 upon activation, as Yoda1 treatment of humanized mice reduces human ILC2-driven AHR. Our studies define Piezo1 as a critical regulator of ILC2s, and we propose the potential of Piezo1 activation as a novel therapeutic approach for the treatment of ILC2-driven allergic asthma.
Clinicopathologic characteristics and outcomes of prostate cancer incidentally discovered at the time of radical cystoprostatectomy: a population-based cohort study
Authors: Kan Wu, Xu Liu, Yaxiong Tang, Xianding Wang, Xiang Li
Journal: International Journal of Surgery (2024)

Objective: This study aimed to comprehensively analyze the clinical characteristics and prognosis of patients with concomitant bladder cancer (BCa) and prostate cancer (PCa) using a large population-based database. Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database (2000–2019), we identified patient with concomitant PCa at the time of radical cystoprostatectomy (RCP). Logistic regression and propensity score matching (PSM) analyses were employed to identify risk factors and mitigate confounders, respectively. Kaplan-Meier survival curves were used to estimate cancer-specific survival (CSS). Results: A total of 14,199 BCa patients undergoing RCP were identified, with 28.8% incidentally discovered to have concurrent PCa. Among them, 89.9% exhibited organ-confined (T1-2) PCa. An increased risk of concomitant tumors was observed among older age, white race, and high tumor grade of BCa. Survival analysis revealed no significant difference in CSS between patients with BCa alone and those with concurrent PCa (5-year CSS rate: 71.3% vs. 67.2%, P =0.076). Subgroup analysis and multivariable analysis, however, indicated that concurrent high-risk PCa adversely impacted survival (5-year CSS rate: 71.3% vs. 63.4%, HR 1.27, 95% CI 1.01-1.58, P =0.038) compared to solitary BCa. Notably, the presence of low/intermediate-risk PCa did not affect survival outcomes ( P =0.584). Conclusion: In conclusion, incidentally discovered PCa in RCP specimens is frequent and characterized by organ-confined presentation, lower PSA levels, and Gleason scores. Patients with concurrent high-risk PCa have a worse prognosis compared to those with solitary BCa, while the presence of low/intermediate-risk PCa does not influence oncological prognosis.
Charting the Course of Targeted α Therapy With First-in-Human, Postadministration Image-Guided Dosimetry and Response Assessment of 212Pb-VMT-α-NET in Metastatic Neuroendocrine Tumors
Authors: Navneet Singh, Nishant Rana, Parul Thakral, Dharmender Malik, Michael K. Schultz, Ishita B. Sen
Journal: Clinical Nuclear Medicine (2024)

Abstract 212 Pb emerges as a compelling in vivo α-particle generator for targeted α therapy due to its favorable half-life ( t 1/2 = 10.6 hours) aligning with the biological half-lives of small peptides and its potent α-particle emissions within the decay series. However, one of the challenges with 212 Pb is to perform appropriate image-guided dosimetry. To date, all the data have been extrapolated from its imaging analog, 203 Pb. We present the first-in-human posttherapy image-guided dosimetric estimates of a single cycle of 212 Pb VMT-α-peptide, administered in a 41-year-old woman with an advanced grade 2 NET. The patient also demonstrated partial response on treatment.
Occult SMARCA4-Deficient Undifferentiated Carcinoma Unmasked by 68Ga-FAPI-46 PET/CT
Authors: Weizhi Xu, Long Zhao, Jiayu Cai, Haojun Chen
Journal: Clinical Nuclear Medicine (2024)

Abstract SMARCA4-deficient undifferentiated tumors (SMARCA4-dUT) are rare and aggressive neoplasms commonly found in male smokers and portend a poor prognosis. In this case, we reported 18 F-FDG and 68 Ga-FAPI-46 PET/CT findings in an occult SMARCA4-dUT located in the left pulmonary hilum along with mediastinal lymph node metastases. 68 Ga-FAPI-46 PET/CT showed superiority over 18 F-FDG for detecting SMARCA4-dUT lesions. This case highlighted that 68 Ga-FAPI-46 PET/CT may be a promising imaging modality in the evaluation of SMARCA4-dUT, particularly for detecting the occult SMARCA4-dUT arising in uncommon sites.
Treatment of Bone Metastases of Breast Cancer With 177Lu-DOTA-IBA
Authors: Jia Deng, Jian Yang, Zixuan Cheng, Yue Chen
Journal: Clinical Nuclear Medicine (2024)

Bone metastasis of breast cancer often presents as osteolytic. 177 Lu-DOTA-ibandronic acid ( 177 Lu-DOTA-IBA) is a new radioactive drug for bone metastasis lesion. We report a case of recurrent intermittent pain due to bone metastasis, who demonstrated a satisfactory therapy response after 2 cycles of 177 Lu-DOTA-IBA. In addition, the patient did not have any observable adverse effects.
Incidental Detection of Synchronous Benign Hepatic and Splenic Hemangiomas on 18F-PSMA PET/CT
Authors: Mohammed Hussain Alsaleh, Ali Saleh Alkhars, Mohammed Albensaad, Abedallatif Alsharif
Journal: Clinical Nuclear Medicine (2024)

Abstract A 51-year-old man with biochemical failure after brachytherapy for prostatic adenocarcinoma (PSA 5 μg/L rising to 6.45 μg/L) underwent a PSMA PET/CT scan. The scan revealed focal 18 F-PSMA activity at the right apex suggestive of local residual or recurrent disease. In addition, 18 F-PSMA images demonstrated 2 focal 18 F-PSMA–avid liver and spleen lesions; both lesions were further evaluated by abdominal MRI, and the final radiological diagnosis was synchronous hepatic and splenic hemangiomas.
Intense PSMA Uptake in Solitary Fibrous Tumor of the Seminal Vesicle
Authors: Qian Zhao, Aisheng Dong, Huamao Ye, Changjing Zuo
Journal: Clinical Nuclear Medicine (2024)

Solitary fibrous tumor arising from the seminal vesicle is very rare. We describe 18 F-PSMA-1007 PET/CT findings in a case of prostate adenocarcinoma with a solitary fibrous tumor of the left seminal vesicle. The solitary fibrous tumor showed intense 18 F-PSMA-1007 uptake mimicking metastatic prostate adenocarcinoma. This case indicates that solitary fibrous tumor may cause false-positive result when using PSMA PET in staging of prostate cancer.
Metabolic tumor burden as a prognostic indicator after neoadjuvant chemotherapy in pancreatic cancer
Authors: Woohyung Lee, Minyoung Oh, Jae Seung Kim, Minkyu Sung, Kwangpyo Hong, Bong Jun Kwak, Yejong Park, Eunsung Jun, Ki Byung Song, Dae Wook Hwang, Jae Hoon Lee, Changhoon Yoo, Kyu-pyo Kim, Inkeun Park, Jae Ho Jeong, Heung-Moon Chang, Baek-Yeol Ryoo, Jung Bok Lee, Song Cheol Kim
Journal: International Journal of Surgery (2024)

Background: There is no standardized assessment for evaluating response although neoadjuvant chemotherapy (NAT) is widely accepted for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). This study was aimed to evaluate NAT response using positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose ( 18 F-FDG-PET/CT) parameters alongside carbohydrate antigen (CA) 19-9 levels. Methods: Patients who underwent surgery after NAT for BRPC and LAPC between 2017 and 2021 were identified. The study assessed the prognostic value of PET-derived parameters after NAT, determining cutoff values using the K-adaptive partitioning method. It created four groups based on the elevation or normalization of PET parameters and CA19-9 levels, comparing survival between these groups. Results: Of 200 eligible patients, FOLFIRINOX and gemcitabine-based NAT were administered in 167 and 34 patients, respectively (mean NAT cycles, 8.3). In a multivariate analysis, metabolic tumor volume (MTV) demonstrated the most robust performance in assessing response (HR 3.11, 95% CI 1.73-5.58, P &lt;0.001) based on cut-off value of 2.4. Patients with decreased MTV had significantly better survival than those with elevated MTV among individuals with CA19-9 levels &lt;37 IU/L (median survival; 35.5 vs. 20.9 mo, P &lt;0.001) and CA19-9 levels ≥37 IU/L (median survival; 34.3 vs. 17.8 mo, P =0.03). In patients suspected to be Lewis antigen negative, predictive performance of MTV was found to be limited ( P =0.84). Conclusion: Elevated MTV is an influential prognostic factor for worse survival, regardless of post-NAT CA19-9 levels. These results could be helpful in identifying patients with a poor prognosis despite normalization of CA19-9 levels after NAT.
Long-term survival outcomes of robotic total gastrectomy for locally advanced proximal gastric cancer: a prospective study
Authors: Qing Zhong, Yi-Hui Tang, Zhi-Yu Liu, Zhi-Quan Zhang, Qi-Chen He, Ping Li, Jian-Wei Xie, Jia-Bin Wang, Jian-Xian Lin, Jun Lu, Qi-Yue Chen, Chao-Hui Zheng, Chang-Ming Huang
Journal: International Journal of Surgery (2024)

Robotic gastrectomy is a safe and feasible approach for gastric cancer (GC); however, its long-term oncological efficacy remains unclear. The authors evaluated the long-term survival outcomes and recurrence patterns of patients with locally advanced proximal GC who underwent robotic total gastrectomy (RTG).