tbuckley/cabot-search huggingface dataset:
Antirheumatic drugs in reproduction, pregnancy, and lactation: a systematic literature review informing the 2024 update of the EULAR recommendations
Authors: Andrea Pluma, Sabrina Hamroun, Linda Rüegg, Irene Cecchi, Malte Kramer, Luis Fernando Perez-Garcia, Tania Rivero, Axel Finckh, Yvette Meissner, Frauke Förger
Journal: Annals of the Rheumatic Diseases (2025)

This study aimed to summarise and update evidence to inform the 2024 update of the European Alliance of Associations for Rheumatology recommendations for the use of antirheumatic drugs in reproduction, pregnancy, and lactation. A systematic literature review (SLR) was performed, including keywords on reproduction, adverse pregnancy outcomes (APOs), and lactation. Two appraised SLRs were the basis for the SLR on drug safety in men. If sufficient data were available, a meta-analysis was performed on maternal drug exposure and the risk of APOs. Of 6680 screened articles, 255 were included in the final analysis. In pregnancy, most evidence was available for biologic disease-modifying antirheumatic drugs (bDMARDs). Meta-analyses with adjusted risk estimates did not reveal APOs or serious infant infections to be associated with tumour necrosis factor inhibitor (TNFi) use. Data on non-TNFi bDMARDs did not raise concerns. In bDMARD-exposed infants, no serious adverse effects to rotavirus live vaccination were reported. Safety of Bacille Calmette-Guérin vaccination in TNFi-exposed infants could be a concern in the first 6 months of life. Regarding oral glucocorticoids, the SLR and meta-analysis using adjusted risk estimates found a dose-dependent association with an increased risk of preterm birth. Nonsteroidal anti-inflammatory drug use could reversibly reduce fecundability. Concerning lactation, available data on various bDMARDs was reassuring. In male patients, available evidence on methotrexate and most other drugs did not reveal adverse effects on sperm quality or birth outcomes. Cyclophosphamide remains the only drug that causes a dose-dependent irreversible infertility. This SLR provides up-to-date evidence to guide the 2024 update of the European Alliance of Associations for Rheumatology recommendations for the use of antirheumatic drugs in reproduction, pregnancy, and lactation.
A Phase 2 PBTC Study of Selumetinib for Recurrent/Progressive Pediatric Low-Grade Glioma: Strata 2, 5, and 6 with Long-term Outcomes on Strata 1, 3, and 4
Authors: Jason Fangusaro, Arzu Onar-Thomas, Tina Young Poussaint, Shelly Lensing, Azra H Ligon, Neal Lindeman, Anuradha Banerjee, Lindsay B Kilburn, Alicia Lenzen, Natasha Pillay-Smiley, Ian F Pollack, Nathan J Robison, Sonia Partap, Ibrahim Qaddoumi, Daniel Landi, David T W Jones, Clinton F Stewart, Maryam Fouladi, Ira J Dunkel
Journal: Neuro-Oncology (2025)

Abstract Background PBTC-029B was a phase 2 trial evaluating efficacy of selumetinib in children with recurrent/progressive low-grade glioma. We report results of strata 2, 5, and 6 with updated survivals for strata 1, 3, and 4. Methods Stratum 2 included recurrent/progressive pilocytic astrocytoma (PA) not associated with neurofibromatosis type-1 (NF1) that screened negative for the BRAF-KIAA1549 fusion and BRAFV600E mutation. Stratum 5 enrolled non-PA that screened positive for one of the BRAF aberrations. Stratum 6 enrolled children who consented to tissue screening, but there was an assay failure. For long-term survivals, stratum 1 included non-NF1 PA positive for one of the BRAF aberrations; stratum 3 included NF1-associated pLGG; and stratum 4 included non-NF1 optic pathway/hypothalamic tumors. Results Stratum 2: among 14 evaluable patients, there was 1 partial response (PR), 7 stable disease (SD) and 6 progressive disease (PD); overall response rate (ORR) was 7.1%. Two-year progression-free survival (PFS)/overall survival (OS) were 57.1%/100%, respectively. Stratum 5: among 23 evaluable patients, there was 1 complete response (CR), 4 PR, 12 SD, and 6 PD; ORR was 21.7%. Two-year PFS/OS were 74.8%/100%, respectively. Stratum 6: among 26 evaluable patients, there were 7 PR, 14 SD, and 5 PD; ORR was 26.9%. Two-year PFS/OS were 72.0%/100%, respectively. The median follow-up for patients on strata 1, 3, and 4 without events are 60.4, 60.4, and 58.1 months, and 5-year PFS/OS were 30.8%/88.9%, 54.2%/100%, and 51.0%/100%, respectively. Conclusions Selumetinib provided stability and responses across many pLGG subgroups, and some patients achieved prolonged disease control without additional therapy.
Lysine-specific demethylase 1 controls key OSCC preneoplasia inducer STAT3 through CDK7 phosphorylation during oncogenic progression and immunosuppression
Authors: Amit Kumar Chakraborty, Rajnikant Dilip Raut, Kisa Iqbal, Chumki Choudhury, Thabet Alhousami, Sami Chogle, Alexa S Acosta, Lana Fagman, Kelly Deabold, Marilia Takada, Bikash Sahay, Vikas Kumar, Manish V Bais
Journal: International Journal of Oral Science (2025)

Abstract Oral squamous cell carcinoma (OSCC) progresses from preneoplastic precursors via genetic and epigenetic alterations. Previous studies have focused on the treatment of terminally developed OSCC. However, the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied. Our study identified lysine-specific demethylase 1 (LSD1) as a crucial promoter of OSCC, demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia. LSD1 inhibition by SP2509 disrupted cell cycle, reduced immunosuppression, and enhanced CD4+ and CD8+ T-cell infiltration. In a feline model of spontaneous OSCC, a clinical LSD1 inhibitor (Seclidemstat or SP2577) was found to be safe and effectively inhibit the STAT3 network. Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling, which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4. Notably, LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422, offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition. This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.
Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagy
Authors: Liang Chen, Pengxiao Hu, Xinhua Hong, Bin Li, Yifan Ping, ShuoMin Chen, Tianle Jiang, Haofu Jiang, Yixin Mao, Yang Chen, Zhongchen Song, Zhou Ye, Xiaoyu Sun, Shufan Zhao, Shengbin Huang
Journal: International Journal of Oral Science (2025)

Abstract Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Single-cell sequencing systematically analyzed the mechanism of Emdogain on the restoration of delayed replantation periodontal membrane
Authors: Yanyi Liu, Yuhao Peng, Lanhui Chen, Yangfan Xiang, Ximu Zhang, Jinlin Song
Journal: International Journal of Oral Science (2025)

Abstract The repair of the periodontal membrane is essential for the successful management of periodontal disease and dental trauma. Emdogain ® (EMD) is widely used in periodontal therapy due to its ability to promote repair. Despite substantial research, the cellular and molecular mechanisms underlying EMD’s effects, particularly at the single-cell resolution, remain incompletely understood. This study established a delayed tooth replantation model in rats to investigate these aspects. Tooth loss rate and degree of loosening were evaluated at 4 and 8 weeks. Micro-CT, HE staining, TRAP staining, and immunofluorescence staining were evaluated to assess EMD’s efficacy. Single-cell sequencing analyses generated single-cell maps that explored enrichment pathways, cell communication, and potential repair mechanisms. Findings indicated that EMD could reduce the rate of tooth loss, promote periodontal membrane repair, and reduce root and bone resorption. Single-cell analysis revealed that EMD promotes the importance of Vtn+ fibroblasts, enhancing matrix and tissue regeneration functions. Additionally, EMD stimulated osteogenic pathways, reduced osteoclastic activity, and promoted angiogenesis-related pathways, particularly bone-related H-type vessel expression in endothelial cells. Gene modules associated with angiogenesis, osteogenesis, and odontoblast differentiation were identified, suggesting EMD might facilitate osteogenesis and odontoblast differentiation by upregulating endothelium-related genes. Immune cell analysis indicated that EMD did not elicit a significant immune response. Cell communication analysis suggested that EMD fostered pro-regenerative networks driven by interactions between mesenchymal stem cells, fibroblasts, and endothelial cells. In conclusion, EMD proves to be an effective root surface therapy agent that supports the restoration of delayed replantation teeth.
NUP62 alleviates senescence and promotes the stemness of human dental pulp stem cells via NSD2-dependent epigenetic reprogramming
Authors: Xiping Wang, Li Wang, Linxi Zhou, Lu Chen, Jiayi Shi, Jing Ge, Sha Tian, Zihan Yang, Yuqiong Zhou, Qihao Yu, Jiacheng Jin, Chen Ding, Yihuai Pan, Duohong Zou
Journal: International Journal of Oral Science (2025)

Abstract Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
Promoting Repigmentation after Epidermal cell suspension grafting and preVENTing the loss of melanocytes using topical ruxolitinib for vitiligo in resistant areas (PREVENT). A prospective monocentric interventional double-blind study
Authors: Pierre-Michel Dugourd, Davide Guardoli, Eric Fontas, Stephany Marie-Luce, Thierry Passeron
Journal: British Journal of Dermatology (2025)

Despite recent advances in treating vitiligo, disappointing results are still observed on difficult-to-treat areas, such as knees, elbows, wrists, hands, and feet. A prospective, monocentric, double-blinded randomized placebo-controlled study was performed to assess the efficac and safety of autologous epidermal cell suspension followed by ruxolutinib cream could repigment resistant ares. Three out of the 19 patients achieved at least 50% repigmentation with the combination approach after 24 weeks, when none was observed with the epidermal grafting alone, but most of the lesions failed to respond. These results suggest that not only the differentiation of melanocytes, but most probably also their proliferation and survival are altered in the difficult to treat areas.
Metastasis Workup for Alveolar Paratesticular Rhabdomyosarcoma
Authors: Amin Saber Tanha, Atena Aghaee, Nasrin Raeisi, Ali Zare, Salman Soltani
Journal: Clinical Nuclear Medicine (2025)

We present a 19-year-old man with alveolar paratesticular rhabdomyosarcoma (RMS) who underwent restaging with both 18 F-fluorodeoxyglucose (FDG) positron-emission tomography (﻿PET)/ computed tomography (﻿CT) and 99m Tc-fibroblast activation protein inhibitor (FAPI)-46 single-photon emission computed tomography (﻿SPECT)/CT after the initial surgery. Despite normal retroperitoneal lymph nodes on CT, 18 F-FDG PET/CT revealed a recurrent mass in the spermatic cord stump and an inguinal lymph node, which was not detected by 99m Tc-FAPI SPECT/CT. Our case highlights the superior efficacy of 18 F-FDG PET/CT compared with 99m Tc-FAPI SPECT/CT in restaging paratesticular RMS, consistent with previous studies demonstrating the utility of 18 F-FDG PET/CT in the initial staging of RMS. This report underscores the importance of selecting the optimal imaging modality for accurate disease assessment and management in this aggressive and rare tumor subtype.
Combination Therapy With 177Lu-FAPI-2286 and Tyrosine Kinase Inhibitor: A Novel Approach for Treating Metastatic Medullary Thyroid Carcinoma
Authors: Nasrin Raeisi, Amin Saber Tanha, Sajad Ataei Azimi, Kamran Aryana
Journal: Clinical Nuclear Medicine (2025)

A 48-year-old man diagnosed with symptomatic metastatic medullary thyroid carcinoma (MTC) presented with dyspnea and a right neck mass which was identified as a metastatic lymph node. Despite initial treatments with sorafenib and chemotherapy, his condition continued to worsen. Evaluation using 99m Tc-FAPI-46 scintigraphy showed favorable uptake in both primary tumor and its metastases, leading to enrollment in a clinical trial for a combination therapy involving sorafenib and 177 Lu-FAPI-2286. After four cycles of this treatment, the patient experienced significant improvement in symptoms, along with notable reductions in serum calcitonin and carcinoembryonic antigen (CEA) levels. This case underscores the potential effectiveness of 177 Lu-FAPI-2286 in managing advanced MTC when conventional therapies prove ineffective.
18F-FDG PET/MRI in Multiple System Atrophy–Parkinsonian Type (MSA-P)
Authors: Faizullah Mashriqi, Alessandro di Rocco, Ana M. Franceschi
Journal: Clinical Nuclear Medicine (2025)

A 64-year-old woman presented with a progressive movement disorder for 4 years, characterized by freezing of gait and left lower extremity discoordination. DaTScan performed 1 year after the presentation was abnormal and consistent with Parkinsonian syndrome. The patient went on to suffer from orthostatic symptomatology resulting in loss of consciousness. She also suffered from urinary incontinence and nocturia. The patient then underwent 18 F-FDG brain PET/MRI, which demonstrated markedly decreased tracer uptake in the bilateral putamina, with accompanying putaminal atrophy, marginal T2-hyperintensity (putaminal rim sign), and central T2* hypointensity. Collectively the imaging findings and clinical presentation are compatible with multiple system atrophy, parkinsonian type (MSA-P).
Brain FDG PET Findings Mimicking Limbic-predominant Age-related TDP-43 Encephalopathy
Authors: Pei Ing Ngam, Yoshimi Anzai, Satoshi Minoshima
Journal: Clinical Nuclear Medicine (2025)

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently recognized neurodegenerative disorder that frequently affects elderly patients and is often misdiagnosed as Alzheimer’s disease. It typically presents with mild memory impairment and disproportionate hippocampal atrophy. FDG PET commonly shows distinct medial temporal lobe hypometabolism, which differs from Alzheimer’s disease. We report a case with FDG PET findings suggestive of LATE; however, CT and MRI revealed hippocampal sulcus remnant cysts instead of hippocampal atrophy. This highlights the critical importance of correlative imaging in distinguishing LATE from other conditions with similar PET findings.
Monoclonal gammopathy of thrombotic significance
Authors: Laurence Mainville, David Coitoru
Journal: British Journal of Dermatology (2025)

Monoclonal gammopathy of thrombotic significance (MGTS) presented with progressive painful purpuric plaques, progressive thrombocytopenia, and acral necrosis in a 64-year-old man. Recognition of MGTS by dermatologists as part of the differential diagnosis of microvascular occlusion syndromes is crucial to guide patients’ care. Management should focus on early recognition of the underlying heamatologic neoplasm, surveillance of thrombotic complications, and initiation of cytoreductive therapy.
Differences in psychologists’ cognitive traits are associated with scientific divides
Authors: Justin Sulik, Nakwon Rim, Elizabeth Pontikes, James Evans, Gary Lupyan
Journal: Nature Human Behaviour (2025)

Abstract Scientific research is often characterized by schools of thought. We investigate whether these divisions are associated with differences in researchers’ cognitive traits such as tolerance for ambiguity. These differences may guide researchers to prefer different problems, tackle identical problems in different ways, and even reach different conclusions when studying the same problems in the same way. We surveyed 7,973 researchers in psychological sciences and investigated links between what they research, their stances on open questions in the field, and their cognitive traits and dispositions. Our results show that researchers’ stances on scientific questions are associated with what they research and with their cognitive traits. Further, these associations are detectable in their publication histories. These findings support the idea that divisions in scientific fields reflect differences in the researchers themselves, hinting that some divisions may be more difficult to bridge than suggested by a traditional view of data-driven scientific consensus.
Palliative Care and Advanced Cardiovascular Disease in Adults: Not Just End-of-Life Care: A Scientific Statement From the American Heart Association
Authors: Lucinda J. Graven, Lisa Kitko, Martha Abshire Saylor, Larry Allen, Angela Durante, Lorraine S. Evangelista, Amy Fiedler, James Kirkpatrick, Lakeisha Mixon, Rachel Wells
Journal: Circulation (2025)

Cardiovascular disease remains a leading cause of morbidity and mortality in adults despite recent scientific advancements. Although people are living longer lives, there may be an adverse impact on quality of life, necessitating a greater need for palliative care services and support. Palliative care for adults with advanced cardiovascular disease has the potential to significantly improve quality of life for individuals living with cardiovascular disease and their informal care partners. Effective communication, shared decision-making, age-friendly care principles, and advance care planning are vital components of palliative care and support comprehensive and holistic care throughout the advanced cardiovascular disease trajectory and across care settings. Current evidence highlights the benefits of palliative care in managing symptoms, reducing psychological distress, and supporting both people with cardiovascular disease and their care partners. However, significant gaps exist in palliative care research related to non–heart failure populations, care partner outcomes, and palliative care implementation in diverse populations. This scientific statement (1) discusses the application of effective communication, shared decision-making, age-friendly care, and advance care planning in advanced cardiovascular disease palliative care; (2) provides a summary of recent evidence related to palliative care and symptom management, quality of life, spiritual and psychological support, and bereavement support in individuals with advanced cardiovascular disease and their care partners; (3) discusses issues involving diversity, equity, and inclusion in cardiovascular disease palliative care; (4) highlights the ethical and legal concerns surrounding palliative care and implanted cardiac devices; and (5) provides strategies for palliative care engagement in adults with advanced cardiovascular disease for the care team.
Novel Truncated Peptide Derived From circCDYL Exacerbates Cardiac Hypertrophy
Authors: Mengyang Li, Wei Ding, Xinyu Fang, Yu Wang, Peiyan Wang, Lin Ye, Shuo Miao, Lin Song, Xiang Ao, Qi Li, Jianxun Wang
Journal: Circulation Research (2025)

BACKGROUND: Circular RNAs (circRNAs) have been gradually revealed to regulate the progression of heart disease in depth, showing their clinical significance. However, a mass of cardiac circRNAs still has not been functionally characterized. We aimed to explore the potential candidates that are involved in pathological cardiac hypertrophy. METHODS: Public substantial RNA-sequencing data of cardiac circRNAs were utilized to search the cardiac hypertrophy–related circRNAs. Cardiomyocyte hypertrophy in vitro was induced by Ang II (angiotensin II) treatment. Mice were subjected to Ang II infusion to induce cardiac hypertrophy in vivo. Gain-of-function and loss-of-function assays were conducted to detect the effect of RNAs or proteins in cardiac hypertrophy. RESULTS: A circRNA derived from the cdyl (chromodomain Y-like) gene was screened out and named circCDYL. Our results showed that the expression of circCDYL in primary rat cardiomyocytes was significantly induced by Ang II. Gain-of-function and loss-of-function assays demonstrated that circCDYL effectively promoted cardiomyocyte hypertrophy in vitro. CircCDYL could encode a ≈100-aa truncated CDYL peptide (tCDYL-100), whose sequence highly overlaps that of full-length CDYL. The translation of tCDYL-100 was activated by N6-methylation of circCDYL under prohypertrophic stimulation. tCDYL-100 fulfilled the prohypertrophic of circCDYL. Mechanistically, tCDYL-100 competed with CDYL for binding REST (RE1-silencing transcription factor) and further disrupted the formation of REST-CDYL-EHMT2 (euchromatic histone-lysine N-methyltransferase 2) transcriptional repression complex, resulting in transcriptional activation of rhoa and nppb . Silence of circCDYL in mouse hearts could inhibit Ang II–induced cardiac hypertrophy, while forced expression of tCDYL-100 could cause cardiac hypertrophy. CONCLUSIONS: In summary, our study uncovered an important circRNA-derived peptide and a regulatory mechanism on transcription mediated by N6-methyladenosine-circRNA-histone methylation in pathological cardiac hypertrophy.