tbuckley/cabot-search huggingface dataset:
Projections for prevalence of Parkinson’s disease and its driving factors in 195 countries and territories to 2050: modelling study of Global Burden of Disease Study 2021
Authors: Dongning Su, Yusha Cui, Chengzhang He, Peng Yin, Ruhai Bai, Jinqiao Zhu, Joyce S T Lam, Junjiao Zhang, Rui Yan, Xiaoqing Zheng, Jiayi Wu, Dong Zhao, Anxin Wang, Maigeng Zhou, Tao Feng
Journal: BMJ (2025)

To predict the global, regional, and national prevalence of Parkinson's disease by age, sex, year, and Socio-demographic Index to 2050 and quantify the factors driving changes in Parkinson's disease cases. Modelling study. Global Burden of Disease Study 2021. Prevalent number, all age prevalence and age standardised prevalence of Parkinson's disease in 2050, and average annual percentage change of prevalence from 2021 to 2050; contribution of population ageing, population growth, and changes in prevalence to the growth in Parkinson's disease cases; population attributable fractions for modifiable factors. 25.2 (95% uncertainty interval 21.7 to 30.1) million people were projected to be living with Parkinson's disease worldwide in 2050, representing a 112% (95% uncertainty interval 71% to 152%) increase from 2021. Population ageing (89%) was predicted to be the primary contributor to the growth in cases from 2021 to 2050, followed by population growth (20%) and changes in prevalence (3%). The prevalence of Parkinson's disease was forecasted to be 267 (230 to 320) cases per 100 000 in 2050, indicating a significant increase of 76% (56% to 125%) from 2021, whereas the age standardised prevalence was predicted to be 216 (168 to 281) per 100 000, with an increase of 55% (50% to 60%) from 2021. Countries in the middle fifth of Socio-demographic Index were projected to have the highest percentage increase in the all age prevalence (144%, 87% to 183%) and age standardised prevalence (91%, 82% to 101%) of Parkinson's disease between 2021 and 2050. Among Global Burden of Disease regions, East Asia (10.9 (9.0 to 13.3) million) was projected to have the highest number of Parkinson's disease cases in 2050, with western Sub-Saharan Africa (292%, 266% to 362%) experiencing the most significant increase from 2021. The ≥80 years age group was projected to have the greatest increase in the number of Parkinson's disease cases (196%, 143% to 235%) from 2021 to 2050. The male-to-female ratios of age standardised prevalence of Parkinson's disease were projected to increase from 1.46 in 2021 to 1.64 in 2050 globally. By 2050 Parkinson's disease will have become a greater public health challenge for patients, their families, care givers, communities, and society. The upward trend is expected to be more pronounced among countries with middle Socio-demographic Index, in the Global Burden of Disease East Asia region, and among men. This projection could serve as an aid in promoting health research, informing policy decisions, and allocating resources.
SHP2 inhibition reduces somatotroph tumor growth in a pre-clinical model
Authors: Facundo García Barberá, Florencia Picech, Laura Cecenarro, Gilda Florencia Mezger, Erica Faure, Natacha Zlocowski, Patricia Calafat, Juan Carlos De Battista, Jorge Humberto Mukdsi, Liliana del Valle Sosa, Juan Pablo Petiti
Journal: Neuro-Oncology (2025)

In somatotroph tumors, over 50% of patients do not respond satisfactorily to the octreotide (OCT) treatment. Stimulation of SSTR2 with OCT triggers anti-proliferative signaling pathways mediated by the phosphatase SHP2. This phosphatase can exercise its functions through the STAT3, with the SHP2/STAT3 subcellular localization being crucial for understanding its mechanisms of action. We investigated the expression of SHP2 in somatotrophs tumors, the role of SHP2 on cell proliferation, its effects on STAT3 phosphorylation, and SHP2/STAT3 subcellular localization, using in vitro and a pre-clinical model. Protein and mRNA expression of SHP2 were evaluated in PitNETs by bioinformatic analysis, IHC and WB. The effect of SHP099 on cell proliferation was determined in GH3 cells, patient derived tumor cells and in a PDX model. The effect of SHP2 on STAT3, AKT and ERK1/2 activation was analyzed by WB, and SHP2/STAT3 subcellular localization was evaluated by IF and MET. We observed increased SHP2 expression in somatotroph tumors being associated with invasiveness. The anti-proliferative effect of OCT and its adaptation after long-term exposure may be driven by the expression of SSTR2 and SHP2. The treatment with SHP099 decreased cell proliferation, tumor volume growth, necrosis as well as the phosphorylation of STAT3-Tyr705, AKT and ERK1/2. We have demonstrated that SHP2 is more expressed in somatotroph tumors, with its pharmacological inhibition resulting in a reduction of both in vitro and in vivo cell proliferation via STAT3 phosphorylation, making this phosphatase a novel clinical target with promising effects on somatotroph tumors.
HumanTestisDB: A Comprehensive Atlas of Testicular Transcriptomics and Cellular Interactions
Authors: Mengjie Wang, Laihua Li, Qing Cheng, Hao Zhang, Zhaode Liu, Yiqiang Cui, Jiahao Sha, Yan Yuan
Journal: Genomics Proteomics & Bioinformatics (2025)

Advances in single-cell technology have enabled the detailed mapping of testicular cell transcriptomes, which is essential for understanding spermatogenesis. However, the fragmented nature of age-specific data from various literature sources has hindered comprehensive analysis. To overcome this, the Human Testis Database (HumanTestisDB) was developed, consolidating multiple human testicular sequencing datasets to address this limitation. Through extensive investigation, 38 unique cell types were identified, providing a detailed perspective on cellular variety. Furthermore, the database systematically categorizes samples into eight developmental stages, offering a structured framework to comprehend the temporal dynamics of testicular development. Each stage features comprehensive maps of cell-cell interactions, elucidating the complex communication network inside the testicular microenvironment at particular developmental stages. Moreover, by facilitating comparisons of interactions among various cell types at different stages, the database permits examining alterations that transpire during critical transitions in spermatogenesis. HumanTestisDB, available at https://shalab.njmu.edu.cn/humantestisdb, offers vital insights into testicular transcriptomics and interactions, serving as an essential resource for advancing research in reproductive biology.
Chinese Position Paper on Biologic Therapy for Chronic Rhinosinusitis With Nasal Polyps
Authors: Mu Xian, Bing Yan, Xicheng Song, Jianjun Chen, Jun Tang, Yan Jiang, Lijia Wan, Wen Liu, Jinmei Xue, Zhiwei Cao, Yafeng Yu, Xiangli Yang, Li Shi, Guangke Wang, Yu Xu, Yucheng Yang, Jing Ye, Luyun Jiang, Fang Quan, Guolin Tan, Feng Liu, Zhendong Xu, Xiaowen Zhang, Jiping Li, Lizhong Su, Yi Yang, Jiangang Fan, Gang He, Li Zhu, Xiangdong Wang, Ming Wang, Shen Shen, Jian Li, Huabin Li, Xin Wei, Hongmeng Yu, Zheng Liu, Ruixia Ma, Huanhai Liu, Jianfeng Liu, Wei Lv, Qintai Yang, Dongdong Zhu, Lei Cheng, Chengshuo Wang, Luo Zhang
Journal: Allergy (2025)

Emerging biologics that selectively target key cytokines present a promising therapeutic alternative for patients suffering from severe, uncontrollable chronic rhinosinusitis with nasal polyps (CRSwNP). Despite the limited availability of registered biologics for CRSwNP treatment in China, the country is experiencing rapid development in this field. It is imperative to standardize the application of biologic agents in CRSwNP management in preparation for their future integration into the CRSwNP care pathway. The Rhinology Group, Chinese Society of Otorhinolaryngology-Head and Neck Surgery; the Rhinology Group, Chinese Medical Doctor Association of Otorhinolaryngology-Head and Neck Surgery; and the Nasal and Ocular Allergy Group, Chinese Society of Allergy have convened an expert panel consisting of principal investigators experienced in clinical trials of biologic treatment for CRSwNP. This expert panel was assembled to discuss the application of biologic agents in patients with CRSwNP in China. Additionally, the latest findings on the pathogenesis of CRSwNP, mechanisms of biologic agents, and efficacy and safety of biologic treatment in patients with CRSwNP were reviewed, with a special emphasis on research evidence from China. The expert panel reached a consensus on several critical issues, including criteria for the prescription, treatment course, and efficacy evaluation from a Chinese perspective. This position paper aims to guide Chinese physicians in the use of biologic agents for patients with CRSwNP. As our experience with biologic treatment continues to grow, this position paper will be further updated.
Ultrasound-Activated Piezoelectric Heterojunction Drives Nanozyme Catalysis to Induce Bacterial Cuproptosis-Like Death and Promote Bone Vascularization and Osseointegration
Authors: Longhai Qiu, Sushuang Ma, Ren Yang, Dengwen Zheng, Yuliang Huang, Zhengwei Zhu, Sijun Peng, Mei Li, Hua Zhong, Feng Peng
Journal: Biomaterials (2025)
En face OCT: Breakthroughs in understanding the pathoanatomy of retinal disease and clinical applications
Authors: Alessandro Feo, Prithvi Ramtohul, Andrea Govetto, Enrico Borrelli, Riccardo Sacconi, Giulia Corradetti, Giuseppe Querques, Mario R Romano, Philip J Rosenfeld, Richard F Spaide, K Bailey Freund, SriniVas Sadda, David Sarraf
Journal: Progress in Retinal and Eye Research (2025)
Gene therapy rescues brain edema and motor function in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts
Authors: Alejandro Brao, Ángela Sánchez, Irina Rodríguez, Javier Del Rey, Silvia Lope-Piedrafita, Esther Prat, Virginia Nunes, Miguel Chillón, Raúl Estévez, Assumpció Bosch
Journal: Molecular Therapy (2025)

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an ultrarare, infantile-onset leukodystrophy characterized by white matter edema for which there is no treatment. More than 70% of diagnosed cases result from biallelic loss-of-function mutations in the astrocyte-specific gene MLC1, leading to early-onset macrocephaly, cerebellar ataxia, epilepsy, and mild cognitive decline. To develop a gene therapy for MLC, we administered an adeno-associated viral vector capable of crossing the murine blood-brain barrier, delivering the human MLC1 cDNA under the control of a human astrocyte-specific promoter, to 10-month-old Mlc1-/- mice. We observed long-term astrocyte-driven expression of MLC1 up to one year after viral vector administration in all brain areas analyzed. Despite the late-stage intervention, in vivo magnetic resonance imaging revealed normalization of water accumulation. Notably, our therapy successfully reversed locomotor deficits in Mlc1-/- mice, as evidenced by improved performance in motor tests assessing cerebellar ataxia-like behaviors. Collectively, these findings not only demonstrate the sustained efficacy of our gene therapy but also highlight the reversibility of vacuolation and motor impairments in Mlc1-/- mice, suggesting that MLC patients could benefit from treatment even after symptom onset.
­­­­­Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma
Authors: Eugenio Morelli, Caroline Fidalgo. Ribeiro, Silvia D. Rodrigues, Claire Gao, Fabio Socciarelli, Domenico Maisano, Vanessa Favasuli, Na Liu, Katia Todoerti, Chandraditya Chakraborty, Yao Yao, Mariateresa Fulciniti, Mehmet Samur, Anil Aktas-Samur, Nicola Amodio, Marcello Turi, Francesca Barello, Johany Penailillo, Cesarina Giallongo, Alessandra Romano, Annamaria Gulla, Kenneth C. Anderson, Giorgio Inghirami, Nikhil C. Munshi, Massimo Loda
Journal: Clinical Cancer Research (2025)

In multiple myeloma (MM), tumor cells reprogram metabolic pathways to sustain growth and monoclonal immunoglobulin production. This study examines acetyl-CoA carboxylase 1 (ACC1), the enzyme driving the rate-limiting step in de novo lipogenesis (DNL), in MM metabolic reprogramming, particularly in c-MYC (MYC)-driven subtypes. ACC1 expression was evaluated across MM genetic subgroups, focusing on MYC translocations. Functional studies using ACC1 inhibitors and genetic knockdown assessed MM cell growth, lipid synthesis, and metabolic homeostasis in vitro and in vivo. The role of MYC overexpression in ACC1 sensitivity was examined, with palmitate rescue experiments. Lipidomic analysis and assessments of ER stress, protein translation, and oxidative damage elucidated underlying mechanisms. ACC1 was overexpressed in MYC-translocated MM. Its inhibition or knockdown reduced MM cell growth in vitro and in vivo, particularly in MYC-overexpressing cells. ACC1 knockdown suppressed de novo lipid synthesis, partially rescued by palmitate. Lipidomic disruptions increased cholesterol ester desaturation and altered phospholipid ratios, inducing ER stress, impaired translation, protein carbonylation, oxidative damage, and apoptosis. ACC1 is a metabolic vulnerability in MYC-driven MM. Inhibiting ACC1 disrupts lipid homeostasis, induces ER stress, and causes oxidative damage, impairing cell survival. Targeting lipid synthesis pathways, especially in MYC-dependent subtypes, offers a promising therapeutic strategy for MM.
Zanubrutinib plus Ixazomib and Dexamethasone in newly diagnosed symptomatic Waldenström macroglobulinemia:a phase II study
Authors: Wenjie Xiong, Yuting Yan, Tingyu Wang, Weiwei Sui, Ying Yu, Tengteng Yu, Rui Lyu, Yi Wang, Wei Liu, Huimin Liu, Gang An, Yan Xu, Wenyang Huang, Dehui Zou, Lugui Qiu, Shuhua Yi
Journal: Clinical Cancer Research (2025)

Waldenström macroglobulinemia (WM) is a rare type of lymphoma, with no optimal treatment. BTK inhibitor have shown promising outcomes, yet achieving deep remission (VGPR or CR) remains challenging and time-limited therapy with proteasome-inhibition has not been reported. We conducted a phase 2 clinical trial (NCT04463953) to evaluate the efficacy and safety of combining zanubrutinib, ixazomib and dexamethasone (ZID) in newly diagnosed WM patients. 27 patients were enrolled in the study. Patients received ZID induction therapy for up to six 28-days' cycles, followed by consolidation therapy up to total 24 cycles. The primary endpoint was the deep remission rate. Overall, 24 of 27 enrolled patients completed induction treatment. One patient (4.2%) achieved CR. 10 patients (41.6%) achieved VGPR. The overall, major and deep remission rates were 100%, 95.8% and 45.8%, respectively. The median time to response was 2 months (range, 1-5). Five of 22 patients had CXCR4 mutation, with no disparity in the deep remission between the patients with/without CXCR4 mutation (40% vs 50%, P=0.594). The median abnormal lymphocyte (7.6% vs 1.6%, P =0.0019) and plasma cells (0.28% to 0.02%, P =0.0306) in bone marrow were significantly reduced after treatment. With a median follow-up of 30.9 months (range, 15-42). The estimated median PFS and OS were 40 months (95% CI:35.5-44.5) and not reached, respectively, with no difference in patients with/without CXCR4mutations. The most common AE was hematological toxicity. ZID regimen might offer deep remission and provided a time-limited BTKi therarpy in WM patients<SPAN style="font-weight: 400;">. </SPAN>.
Pembrolizumab in combination with binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer
Authors: Saranya Chumsri, Joseph J. Larson, Emily Liu, Kathleen S. Tenner, Daniel Adams, Morgan T. Weidner, Amanda N. Arnold, Dana L. Haley, Pooja Advani, Kostandinos Sideras, Alvaro Moreno-Aspitia, E. Aubrey Thompson, Edith A. Perez, Keith L. Knutson
Journal: Clinical Cancer Research (2025)

Activation of the RAS/MAPK pathway is associated with reduced tumor-infiltrating lymphocytes and poor outcomes in triple-negative breast cancer (TNBC). Previous studies demonstrated that inhibition of the MAPK pathway with a MEK inhibitor is synergistic with immune checkpoint inhibitors. We conducted a phase I/II trial of pembrolizumab and binimetinib in patients with metastatic TNBC with ≤ 3 prior lines of therapy. There were two dose levels (DL) with binimetinib at 45 mg at DL 0 and 30 mg at DL -1. The recommended phase II dose was the standard dose of pembrolizumab with binimetinib 30 mg twice daily. The objective response rate (ORR) was 30.4%, with a numerically higher ORR in patients without liver metastasis at 45.5%. Among patients who achieved objective responses, 80% had a duration of response > 12 months and ongoing even after stopping treatment (5.4 - 69.0 months). Patients with PD-L1-positive tumors (CPS ≥ 10) were more likely to respond with an ORR of 66.7%. However, clinical benefit was observed in 25% of patients with PD-L1-negative tumors. Consistent with preclinical studies, 4 out of 6 patients with clinical benefit had either increased PD-L1 or decreased p-ERK expressions in serial circulating cancer-associated macrophage-like cells (CAMLs) after starting binimetinib. Pembrolizumab and binimetinib at 30 mg are safe with manageable toxicities. Promising activity was observed in patients without liver metastases. Future larger clinical trials are warranted to further evaluate the efficacy of this chemotherapy-free combination.
Radiation Dose-Volume Effects on Negative Tumor-Draining Lymph Nodes Impacted T-Cell Activation and Prognosis in Esophageal Cancer with Chemoradiotherapy
Authors: Ihsuan Tseng, Yun Chen, Dashan Ai, Zhengfei Zhu, Weixin Zhao, Min Fan, Ling Li, Hongcheng Zhu, Fangfang Li, Yang Xu, Lu Yu, Zezhou Wang, Junqi Wang, Qi Liu, Jiaying Deng, Shengnan Hao, Qingsong Fan, Jinjun Ye, Jialiang Zhou, Chaoyang Wu, Huarong Tang, Qin Lin, Jiancheng Li, Yunhai Li, Shihong Wei, Hui Luo, Jianzhong Cao, Xiangpeng Zheng, Guang Huang, Yuwei Zheng, Bo Ping, Kuaile Zhao
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Preclinical model found that elective nodal irradiation (ENI) attenuated the efficacy of radiotherapy and radio-immunotherapy. However, limited clinical studies have explored the correlation between radiation dose-volume parameters of negative tumor draining lymph nodes (TDLNs) and T-cell activation/prognosis for cancer patients treated with definitive radio(chemo)therapy. Experimental Design: Patients with locally advanced esophageal cancer undergoing definitive chemoradiotherapy (CRT) were selected from two prospective trials. Dose-volume parameters of TDLN as well as other lymphocyte-related organs at risk (LOARs) and lymphocyte subsets such as CD3-CD19+ B cells, CD8+CD28+ T cells, and activated T cells (CD3+CD8+HLA-DR+) before and at the end of radiotherapy (RT) were collected. Logistic analysis was utilized to correlate dose-volume parameters with reductions in lymphocyte subsets. Prognosis of TDLN irradiation was investigated through Kaplan-Meier analysis and Cox hazards models. Results: Among 512 patients, the median mean dose of TDLN and negative non-TDLN was 25.6 Gy and 15.1 Gy, respectively. Multivariable analyses indicated TDLN V15 &amp;gt;50% was an independent predictor of poorer local-recurrence free survival (HR, 1.31; p=0.029) and distant-metastasis free survival (HR, 1.39; p&amp;lt;0.001), as well as greater reductions in CD3-CD19+ B cells (OR, 1.98; p=0.002), CD8+CD28+ T cells (OR, 3.42; p&amp;lt;0.001) and CD3+CD8+HLA-DR+ T cells (OR, 4.67; p=0.002) post-RT. Conclusions: A higher radiation dose-volume parameter of TDLNs in esophageal cancer patients undergoing CRT was significantly associated with suppression of T-cell activation and a worse prognosis. Limiting the percentage of TDLN V15 may be beneficial for improving the prognosis of CRT with or without PD-1 inhibitors.
Non-Image-Forming Functions of Intrinsically Photosensitive Retinal Ganglion Cells
Authors: Jianjun Meng, Xiaodan Huang, Chaoran Ren, Tian Xue
Journal: Annual Review of Neuroscience (2025)

Life on this planet is heavily influenced by light, the most critical external environmental factor. Mammals perceive environmental light mainly through three types of photoreceptors in the retina-rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). The latest discovered ipRGCs are particularly sensitive to short-wavelength light and have a unique phototransduction mechanism, compared with rods and cones. Piles of evidence suggest that ipRGCs mediate a series of light-regulated physiological functions such as circadian rhythms, sleep, metabolic homeostasis, mood, development, and higher cognitions, collectively known as non-image-forming vision. Recent advances in systems neuroscience, driven by modern neural circuit tools, have illuminated the structure and function of the neural pathways connecting the retina to subcortical regions, highlighting their involvement in an array of non-image-forming functions. Here we review key discoveries and recent progress regarding the neural circuit mechanisms employed by ipRGCs to regulate diverse biological functions and provide insights into unresolved scientific questions in this area.
Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols
Authors: Tricia R Cottrell, Michael T Lotze, Alaa Ali, Carlo B Bifulco, Christian M Capitini, Laura Q M Chow, Anthony R Cillo, Deborah Collyar, Leslie Cope, Julie Stein Deutsch, Genia Dubrovsky, Sacha Gnjatic, Denise Goh, Susan Halabi, Gary Kohanbash, Holden T Maecker, Saman Maleki Vareki, Sarah Mullin, Barbara Seliger, Janis Taube, Wim Vos, Joe Yeong, Kristin G Anderson, Tullia C Bruno, Codruta Chiuzan, Ivan Diaz-Padilla, Elizabeth Garrett-Mayer, Isabella C Glitza Oliva, Paola Grandi, Elizabeth G Hill, Brian P Hobbs, Yana G Najjar, Phyllis Pettit Nassi, Virgil H Simons, Sumit K Subudhi, Ryan J Sullivan, Chris H Takimoto
Journal: Journal for ImmunoTherapy of Cancer (2025)

Immunotherapy of cancer is now an essential pillar of treatment for patients with many individual tumor types. Novel immune targets and technical advances are driving a rapid exploration of new treatment strategies incorporating immune agents in cancer clinical practice. Immunotherapies perturb a complex system of interactions among genomically unstable tumor cells, diverse cells within the tumor microenvironment including the systemic adaptive and innate immune cells. The drive to develop increasingly effective immunotherapy regimens is tempered by the risk of immune-related adverse events. Evidence-based biomarkers that measure the potential for therapeutic response and/or toxicity are critical to guide optimal patient care and contextualize the results of immunotherapy clinical trials. Responding to the lack of guidance on biomarker testing in early-phase immunotherapy clinical trials, we propose a definition and listing of essential biomarkers recommended for inclusion in all such protocols. These recommendations are based on consensus provided by the Society for Immunotherapy of Cancer (SITC) Clinical Immuno-Oncology Network (SCION) faculty with input from the SITC Pathology and Biomarker Committees and the Journal for ImmunoTherapy of Cancer readership. A consensus-based selection of essential biomarkers was conducted using a Delphi survey of SCION faculty. Regular updates to these recommendations are planned. The inaugural list of essential biomarkers includes complete blood count with differential to generate a neutrophil-to-lymphocyte ratio or systemic immune-inflammation index, serum lactate dehydrogenase and albumin, programmed death-ligand 1 immunohistochemistry, microsatellite stability assessment, and tumor mutational burden. Inclusion of these biomarkers across early-phase immunotherapy clinical trials will capture variation among trials, provide deeper insight into the novel and established therapies, and support improved patient selection and stratification for later-phase clinical trials.