tbuckley/cabot-search huggingface dataset:
Neurocognitive outcomes and functional independence in adult survivors of childhood medulloblastoma diagnosed over 3 decades
Authors: Chiara Papini, Sedigheh Mirzaei, Mengqi Xing, Ingrid Tonning Olsson, Ralph Salloum, Peter M K de Blank, Katharine R Lange, Tricia Z King, Deokumar Srivastava, Wendy M Leisenring, Rebecca M Howell, Kevin C Oeffinger, Leslie L Robison, Gregory T Armstrong, Kevin R Krull, Tara M Brinkman
Journal: Neuro-Oncology (2024)

Treatment of childhood medulloblastoma has evolved to reduce neurotoxicity while improving survival. However, the impact of evolving therapies on late neurocognitive outcomes and adult functional independence remains unknown. Adult survivors of childhood medulloblastoma (n = 505; median [minimum-maximum] age, 29 [18-46] years) and sibling controls (n = 727; 32 [18-58] years) from the Childhood Cancer Survivor Study completed surveys assessing neurocognitive problems and chronic health conditions (CHCs). Treatment exposures were categorized as historical (craniospinal irradiation [CSI] ≥ 30 Gy, no chemotherapy), standard-risk (CSI > 0 to <30 Gy + chemotherapy) and high-risk (CSI ≥ 30 Gy + chemotherapy) therapy. Latent class analysis identified patterns of functional independence using employment, independent living, assistance with routine/personal care needs, driver's license, and marital/partner status. Multivariable models estimated the risk of neurocognitive impairment in survivors versus siblings and by treatment exposure group, and associations between neurocognitive impairment, CHCs, and functional independence. Survivors in each treatment exposure group had a 4- to 5-fold elevated risk of impaired memory and task efficiency compared to siblings. Contemporary risk-based therapies did not confer lower risk compared to historical therapy. Survivors treated in the 1990s had a higher risk of memory impairment (relative risk [RR] 2.24, 95% confidence interval 1.39-3.60) compared to survivors treated in the 1970s. Sensorimotor, hearing problems, and seizures were associated with 33-34%, 25-26%, and 21-42% elevated risk of task efficiency and memory impairment, respectively. Treatment-related CHCs and neurocognitive impairment were associated with nonindependence. Despite treatment changes, long-term survivors of childhood medulloblastoma remain at risk for neurocognitive impairment, which was associated with CHCs. Neurocognitive surveillance after contemporary regimens is imperative.
Bioactive sucralfate-based microneedles promote wound healing through reprogramming macrophages and protecting endogenous growth factors
Authors: Zhicheng Le, Mayk Caldas Ramos, Yufeng Shou, Renee R. Li, Hong Sheng Cheng, Clarisse JM. Jang, Ling Liu, Chencheng Xue, Xianlei Li, Hong Liu, Chwee Teck Lim, Nguan Soon Tan, Andrew D. White, Christopher John Charles, Yongming Chen, Zhijia Liu, Andy Tay
Journal: Biomaterials (2024)
Cold versus hot snare endoscopic mucosal resection for large (≥15 mm) flat non-pedunculated colorectal polyps: a randomised controlled trial
Authors: Timothy O’Sullivan, Oliver Cronin, W Arnout van Hattem, Francesco Vito Mandarino, Julia L Gauci, Clarence Kerrison, Anthony Whitfield, Sunil Gupta, Eric Lee, Stephen J Williams, Nicholas Burgess, Michael J Bourke
Journal: Gut (2024)

Background and aims Conventional hot snare endoscopic mucosal resection (H-EMR) is effective for the management of large (≥20 mm) non-pedunculated colon polyps (LNPCPs) however, electrocautery-related complications may incur significant morbidity. With a superior safety profile, cold snare EMR (C-EMR) of LNPCPs is an attractive alternative however evidence is lacking. We conducted a randomised trial to compare the efficacy and safety of C-EMR to H-EMR. Methods Flat, 15–50 mm adenomatous LNPCPs were prospectively enrolled and randomly assigned to C-EMR or H-EMR with margin thermal ablation at a single tertiary centre. The primary outcome was endoscopically visible and/or histologically confirmed recurrence at 6 months surveillance colonoscopy. Secondary outcomes were clinically significant post-EMR bleeding (CSPEB), delayed perforation and technical success. Results 177 LNPCPs in 177 patients were randomised to C-EMR arm (n=87) or H-EMR (n=90). Treatment groups were equivalent for technical success 86/87 (98.9%) C-EMR versus H-EMR 90/90 (100%); p=0.31. Recurrence was significantly greater in C-EMR (16/87, 18.4% vs 1/90, 1.1%; relative risk (RR) 16.6, 95% CI 2.24 to 122; p&lt;0.001). Delayed perforation (1/90 (1.1%) vs 0; p=0.32) only occurred in the H-EMR group. CSPEB was significantly greater in the H-EMR arm (7/90 (7.8%) vs 1/87 (1.1%); RR 6.77, 95% CI 0.85 to 53.9; p=0.034). Conclusion Compared with H-EMR, C-EMR for flat, adenomatous LNPCPs, demonstrates superior safety with equivalent technical success. However, endoscopic recurrence is significantly greater for cold snare resection and is currently a limitation of the technique. Trial registration number NCT04138030
Most cutaneous squamous cell carcinoma recurrences occur in the first 3 years after diagnosis: A multicenter retrospective cohort study
Authors: Emily E. Granger, Nina A. Ran, Morgan K. Groover, Shlomo A. Koyfman, Allison T. Vidimos, Ashley Wysong, David R. Carr, Kathryn T. Shahwan, Kelsey E. Hirotsu, John A. Carucci, Joi B. Carter, Javier Cañueto, Fabio Muradás Girardi, Aaron R. Mangold, Divya Srivastava, David G. Brodland, John A. Zitelli, Tyler J. Willenbrink, Emily S. Ruiz
Journal: Journal of the American Academy of Dermatology (2024)
Environmental exposures associated with early childhood recurrent wheezing in the mother and child in the environment birth cohort: a time-to-event study
Authors: Kareshma Asharam, Aweke A Abebaw Mitku, Lisa Ramsay, Prakash Mohan Jeena, Rajen N Naidoo
Journal: Thorax (2024)

Background Antenatal factors and environmental exposures contribute to recurrent wheezing in early childhood. Aim To identify antenatal and environmental factors associated with recurrent wheezing in children from birth to 48 months in the mother and child in the environment cohort, using time-to-event analysis. Method Maternal interviews were administered during pregnancy and postnatally and children were followed up from birth to 48 months (May 2013–October 2019). Hybrid land-use regression and dispersion modelling described residential antenatal exposure to nitrogen dioxide (NO 2 ) and particulate matter of 2.5 µm diameter (PM 2.5 ). Wheezing status was assessed by a clinician. The Kaplan-Meier hazard function and Cox-proportional hazard models provided estimates of risk, adjusting for exposure to environmental tobacco smoke (ETS), maternal smoking, biomass fuel use and indoor environmental factors. Results Among 520 mother–child pairs, 85 (16%) children, had a single wheeze episode and 57 (11%) had recurrent wheeze. Time to recurrent wheeze (42.9 months) and single wheeze (37.8 months) among children exposed to biomass cooking fuels was significantly shorter compared with children with mothers using electricity (45.9 and 38.9 months, respectively (p=0.03)). Children with mothers exposed to antenatal ETS were 3.8 times more likely to have had recurrent wheeze compared with those not exposed (adjusted HR 3.8, 95% CI 1.3 to 10.7). Mean birth month NO 2 was significantly higher among the recurrent wheeze category compared with those without wheeze. NO 2 and PM 2.5 were associated with a 2%–4% adjusted increased wheezing risk. Conclusion Control of exposure to ETS and biomass fuels in the antenatal period is likely to delay the onset of recurrent wheeze in children from birth to 48 months.
Antibiotic pharmacokinetics in infected pleural effusions
Authors: David T Arnold, Liam Read, Oliver Waddington, Fergus W Hamilton, Sonia Patole, Jessica Hughes, Alice Milne, Alan Noel, Mark Bayliss, Nicholas A Maskell, Alasdair MacGowan
Journal: Thorax (2024)

Pleural infection is usually treated with empirical broad-spectrum antibiotics, but limited data exist on their penetrance into the infected pleural space. We performed a pharmacokinetic study analysing the concentration of five intravenous antibiotics across 146 separate time points in 35 patients (amoxicillin, metronidazole, piperacillin-tazobactam, clindamycin and cotrimoxazole). All antibiotics tested, apart from co-trimoxazole, reach pleural fluid levels equivalent to levels within the blood and well above the relevant minimum inhibitory concentrations. The results demonstrate that concerns about the penetration of commonly used antibiotics, apart from co-trimoxazole, into the infected pleural space are unfounded.
Acod1-mediated inhibition of aerobic glycolysis suppresses osteoclast differentiation and attenuates bone erosion in arthritis
Authors: Katerina Kachler, Darja Andreev, Shreeya Thapa, Dmytro Royzman, Andreas Gießl, Shobika Karuppusamy, Mireia Llerins Perez, Mengdan Liu, Jörg Hofmann, Arne Gessner, Xianyi Meng, Simon Rauber, Alexander Steinkasserer, Martin Fromm, Georg Schett, Aline Bozec
Journal: Annals of the Rheumatic Diseases (2024)

Metabolic changes are crucially involved in osteoclast development and may contribute to bone degradation in rheumatoid arthritis (RA). The enzyme aconitate decarboxylase 1 (Acod1) is known to link the cellular function of monocyte-derived macrophages to their metabolic status. As osteoclasts derive from the monocyte lineage, we hypothesised a role for Acod1 and its metabolite itaconate in osteoclast differentiation and arthritis-associated bone loss.
Efficacy and safety of first-line biological DMARDs in rheumatoid arthritis patients with chronic kidney disease
Authors: Yusuke Yoshimura, Masayuki Yamanouchi, Hiroki Mizuno, Daisuke Ikuma, Ryo Koizumi, Shigekazu Kurihara, Yuki Oba, Tatsuya Suwabe, Yuichiro Sawada, Hisashi Kamido, Hisashi Sugimoto, Masato Mizuta, Akinari Sekine, Eiko Hasegawa, Yoshifumi Ubara, Naoki Sawa
Journal: Annals of the Rheumatic Diseases (2024)

To evaluate the efficacy and safety of first-line biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) with chronic kidney disease (CKD), including those undergoing haemodialysis (HD).
Final outcome analysis from the phase II TUXEDO-1 trial of trastuzumab-deruxtecan in HER2-positive breast cancer patients with active brain metastases
Authors: Rupert Bartsch, Anna Sophie Berghoff, Julia Furtner, Maximilian Marhold, Elisabeth Sophie Bergen, Sophie Roider-Schur, Maximilian Johannes Mair, Angelika Martina Starzer, Heidrun Forstner, Beate Rottenmanner, Marie-Bernadette Aretin, Karin Dieckmann, Zsuzsanna Bago-Horvath, Helmuth Haslacher, Georg Widhalm, Aysegül Ilhan-Mutlu, Christoph Minichsdorfer, Thorsten Fuereder, Thomas Szekeres, Leopold Oehler, Birgit Gruenberger, Georg Pfeiler, Christian Singer, Ansgar Weltermann, Luzia Berchtold, Matthias Preusser
Journal: Neuro-Oncology (2024)

Brain metastases (BM) are a devastating complication of HER2-positive metastatic breast cancer (BC) and treatment strategies providing optimized local and systemic disease control are urgently required. The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) over trastuzumab emtansine but data regarding intracranial activity is limited. In the primary outcome analysis of TUXEDO-1, a high intracranial response rate (RR) was reported with T-DXd. Here, we report the final PFS and OS results.
Contained hepatic vascular injuries following liver trauma: a retrospective monocentric study and review of the literature
Authors: Sébastien Frey, Imad Bentellis, Jacques Sedat, Florent Poirier, Patrick Baque, Damien Massalou
Journal: International Journal of Surgery (2024)

Over the past thirty years, there has been a major shift in the management of liver trauma. Contained hepatic vascular injuries (CHVI), including pseudoaneurysms and arteriovenous fistulas, are often feared because of the risk of secondary hemorrhage. However, little is known about CHVI. There are no guidelines for their management. Our aim was to validate the risk factors for CHVI, to identify the associated morbidities, and to establish a management protocol.
Unlocking the therapeutic potential: odyssey of induced pluripotent stem cells (iPSC) in precision cell therapies
Authors: Popat Mohite, Roshan Dave, Arati Budhar, Shubham Munde, Abhijeet Puri, Shruti Bagchi Ghosh, Taha Alqahtani, Humood Al Shmrany, Ajoy Kumer, Bikram Dhara
Journal: International Journal of Surgery (2024)

This review explores the application of induced pluripotent stem cells (iPSCs) in regenerative medicine. The therapeutic significance of iPSC-derived cell therapy within regenerative medicine, emphasizes their reprogramming process and crucial role in cellular differentiation while setting the purpose and scope for the comprehensive exploration of iPSC-derived cell therapy. The subsequent sections intricately examine iPSC-derived cell therapy, unravelling the diverse derivatives of iPSCs and striking a delicate balance between advantages and limitations in therapeutic applications. Mechanisms of action, revealing how iPSC-derived cells seamlessly integrate into tissues, induce regeneration, and contribute to disease modeling and drug screening advancements is discussed. The analysis extends to clinical trials, shedding light on outcomes, safety considerations, and ethical dimensions. Challenges and concerns, including the risk of tumorigenesis and scalability issues, are explored. The focus extends to disease-specific applications, showcasing iPSC-derived cell therapy as a promising avenue for various medical conditions, supported by illustrative case studies. Future directions and research needs are outlined, identifying areas for further exploration, safety considerations and potential enhancements that will shape the future landscape of iPSC-derived therapies. In conclusion, this review provides significant understanding of iPSC-derived cell therapy's status, that contemplates the implications for regenerative medicine and personalized treatment using iPSCs, offering a comprehensive perspective on the evolving field within the confines of a dynamic and promising scientific frontier.
A 10-year mono-center study on patients with burns ≥70% TBSA: prediction model construction and multi-center validation: retrospective cohort
Authors: Runzhi Huang, Yuntao Yao, Linhui Li, Xirui Tong, Yifan Liu, Junqiang Li, Dayuan Xu, Minjuan Wu, Zhengyan Chang, Long Xu, Shuyuan Xian, Sujie Xie, Wei Zhang, Jianyu Lu, Yuwei Lu, Bingnan Lu, Siqiao Wang, Weijin Qian, Hanlin Sun, Minghao Jin, Jie Huang, Yiting Yang, Yushu Zhu, Yuanan Li, Xinya Guo, Minyi Gu, Luofeng Jiang, Pengfei Luo, Shichu Xiao, Shizhao Ji
Journal: International Journal of Surgery (2024)

Burn injuries with ≥70% total body surface area (TBSA) are especially acute and life-threatening, leading to severe complications and terrible prognosis, while a powerful model for prediction of overall survival (OS) is lacked. The objective of this study is to identify prognostic factors for the OS of patients with burn injury ≥70% TBSA, construct and validate a feasible predictive model.
Low-to-moderate alcohol consumption is associated with increased fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease
Authors: David Marti-Aguado, José Luis Calleja, Eduardo Vilar-Gomez, Paula Iruzubieta, Juan Carlos Rodríguez-Duque, María Del Barrio, Laura Puchades, Jesus Rivera-Esteban, Christie Perelló, Angela Puente, Concepción Gomez-Medina, Desamparados Escudero-García, Miguel A. Serra, Ramon Bataller, Javier Crespo, María Teresa Arias-Loste
Journal: Journal of Hepatology (2024)
Developing a gender affirming health response for trans and gender diverse Australians: a qualitative study
Authors: Isabella K. Windt, Amy B. Mullens, Joseph Debattista, Melinda Stanners, Annette Brömdal
Journal: International Journal of Transgender Health (2024)

Introduction As trans and gender diverse populations experience disproportionately higher rates of discrimination, violence, mental health challenges, unemployment, and financial hardship, it is important to develop an evidence-based public health response for trans and gender diverse people seeking gender-affirming surgery (GAS). Resourcing and pathways for access vary across Australian states, with little research exploring the experiences of trans and gender-diverse people seeking GAS in Australia.
Engineering biomimetic silk fibroin hydrogel scaffolds with “organic-inorganic assembly” strategy for rapid bone regeneration
Authors: Renjie Liang, Rui Li, Weidong Mo, Xianzhu Zhang, Jinchun Ye, Chang Xie, Wenyue Li, Zhi Peng, Yuqing Gu, Yuxuan Huang, Shufang Zhang, Xiaozhao Wang, Hongwei Ouyang
Journal: Bioactive Materials (2024)

Although natural polymers have been widely used in constructing bone scaffolds, it still remains challenging to fabricate natural polymer-derived bone scaffolds with biomimetic mechanical properties as well as outstanding osteogenic properties for large-size and weight-bearing bone defects regeneration. Herein, an "organic-inorganic assembly" strategy is developed to construct silk fibroin (SF)-based bone scaffolds with the aforementioned merits. After secondary structure reshuffling, the 3.3-fold increment of β-sheet structures in SF hydrogel resulted in a 100-fold improvement of mineral-assembly efficacy via influencing the ion adsorption process and providing templates for mineral growth. Notably, abundant minerals were deposited within the hydrogel and also on the surface, which indicated entire mineral-assembly, which ensured the biomimetic mechanical properties of the digital light processing 3D printed SF hydrogel scaffolds with haversian-mimicking structure.
Macrophage-derived extracellular vesicles regulate skeletal stem/progenitor Cell lineage fate and bone deterioration in obesity
Authors: Chen He, Chen Hu, Wen-Zhen He, Yu-Chen Sun, Yangzi Jiang, Ling Liu, Jing Hou, Kai-Xuan Chen, Yu-Rui Jiao, Mei Huang, Min Huang, Mi Yang, Qiong Lu, Jie Wei, Chao Zeng, Guang-Hua Lei, Chang-Jun Li
Journal: Bioactive Materials (2024)

Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue and the underlying mechanisms are still unclear. Here, we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles, leading to a switch in skeletal stem/progenitor cell (SSPC) differentiation between osteoblasts and adipocytes and bone deterioration. Bone marrow macrophage (BMM)-secreted extracellular vesicles (BMM-EVs) from obese mice induced bone deterioration (decreased bone volume, bone microstructural deterioration, and increased adipocyte numbers) when administered to lean mice. Conversely, BMM-EVs from lean mice rejuvenated bone deterioration in obese recipients. We further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates, miR-140 (with the function of promoting adipogenesis) and miR-378a (with the function of enhancing osteogenesis) coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Pparα-Abca1 axis. BMM miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration, while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean mice. BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration. More importantly, we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system, and this approach rescued bone deterioration in obese mice. Thus, our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.
The long but necessary road to responsible use of large language models in healthcare research
Authors: Jethro C. C. Kwong, Serena C. Y. Wang, Grace C. Nickel, Giovanni E. Cacciamani, Joseph C. Kvedar
Journal: npj Digital Medicine (2024)

Large language models (LLMs) have shown promise in reducing time, costs, and errors associated with manual data extraction. A recent study demonstrated that LLMs outperformed natural language processing approaches in abstracting pathology report information. However, challenges include the risks of weakening critical thinking, propagating biases, and hallucinations, which may undermine the scientific method and disseminate inaccurate information. Incorporating suitable guidelines (e.g., CANGARU), should be encouraged to ensure responsible LLM use.
Competing interests: digital health and indigenous data sovereignty
Authors: Ashley Cordes, Marieke Bak, Mataroria Lyndon, Maui Hudson, Amelia Fiske, Leo Anthony Celi, Stuart McLennan
Journal: npj Digital Medicine (2024)

Digital health is increasingly promoting open health data. Although this open approach promises a number of benefits, it also leads to tensions with Indigenous data sovereignty movements led by Indigenous peoples around the world who are asserting control over the use of health data as a part of self-determination. Digital health has a role in improving access to services and delivering improved health outcomes for Indigenous communities. However, we argue that in order to be effective and ethical, it is essential that the field engages more with Indigenous peoples´ rights and interests. We discuss challenges and possible improvements for data acquisition, management, analysis, and integration as they pertain to the health of Indigenous communities around the world.
Off-the-shelf CAR-NK cells targeting immunogenic cell death marker ERp57 execute robust antitumor activity and have a synergistic effect with ICD inducer oxaliplatin
Authors: Liuhai Zheng, Huifang Wang, Jihao Zhou, Guangwei Shi, Jingbo Ma, Yuke Jiang, Zhiyu Dong, Jiexuan Li, Yuan-Qiao He, Dinglan Wu, Jichao Sun, Chengchao Xu, Zhijie Li, Jigang Wang
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Chimeric antigen receptor natural killer (CAR-NK) therapy holds great promise for treating hematologic tumors, but its efficacy in solid tumors is limited owing to the lack of suitable targets and poor infiltration of engineered NK cells. Here, we explore whether immunogenic cell death (ICD) marker ERp57 translocated from endoplasmic reticulum to cell surface after drug treatment could be used as a target for CAR-NK therapy. Methods To target ERp57, a VHH phage display library was used for screening ERp57-targeted nanobodies (Nbs). A candidate Nb with high binding affinity to both human and mouse ERp57 was used for constructing CAR-NK cells. Various in vitro and in vivo studies were performed to assess the antitumor efficacy of the constructed CAR-NK cells. Results We demonstrate that the translocation of ERp57 can not only be induced by low-dose oxaliplatin (OXP) treatment but also is spontaneously expressed on the surface of various types of tumor cell lines. Our results show that G6-CAR-NK92 cells can effectively kill various tumor cell lines in vitro on which ERp57 is induced or intrinsically expressed, and also exhibit potent antitumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the antitumor activity of G6-CAR-NK92 cells is synergistically enhanced by the low-dose ICD-inducible drug OXP. Conclusion Collectively, our findings suggest that ERp57 can be leveraged as a new tumor antigen for CAR-NK targeting, and the resultant CAR-NK cells have the potential to be applied as a broad-spectrum immune cell therapy for various cancers by combining with ICD inducer drugs.