tbuckley/cabot-search huggingface dataset:
Interventional Removal of Travelling Microthrombi Using Targeted Magnetic Microbubble
Authors: Yongjian Li, Zujie Gao, Xiaobing Zheng, Yunfan Pan, Jinlong Xu, Yan Li, Haosheng Chen
Journal: Advanced Healthcare Materials (2024)

Microthrombus is one of the major causes of the sequelae of Corona Virus Disease 2019 (COVID-19 and leads to subsequent embolism and necrosis. Due to their small size and irregular movements, the early detection and efficient removal of microthrombi in vivo remain a great challenge. In this work, an interventional method is developed to identify and remove the traveling microthrombi using targeted-magnetic-microbubbles (TMMBs) and an interventional magnetic catheter. The thrombus-targeted drugs are coated on the TMMBs and magnetic nanoparticles are shelled inside, which allow not only targeted adhesion onto the traveling microthrombi, but also the effective capture by the magnetic catheter in the vessel. In the proof-of-concept experiments in the rat models, the concentration of microthrombus is reduced by more than 60% in 3 min, without damaging the organs. It is a promising method for treating microthrombus issues.
‘When you do not feel comfortable in your skin, you cannot get out of it’; a qualitative interview study exploring psychosocial impact and coping strategies among patients with prurigo nodularis
Authors: Louisa Schielein, Stefanie Ziehfreund, Tilo Biedermann, Alexander Zink
Journal: British Journal of Dermatology (2024)

Prurigo nodularis (PN) is a disease associated with severe chronic pruritus and therefore causes a substantial impact on quality of life. This study aimed to explore the psychosocial burden of PN and the coping mechanisms employed by affected individuals to manage symptoms associated with the condition. In summary, patients reported a profound impact on various aspects of their lives, including mental wellbeing, relationships, self-perception, leisure activities, occupation, sleep patterns and clothing choices. Further, the disease led to social avoidance and isolation in patients.
Exosomes derived from tendon stem/progenitor cells enhance tendon-bone interface healing after rotator cuff repair in a rat model
Authors: Yanwei He, Shihao Lu, Wenbo Chen, Li Yang, Fangqi Li, Peng Zhou, Zan Chen, Renwen Wan, Zifan Zhang, Yaying Sun, Jinrong Lin, Yisheng Chen, Zhiwen Luo, Chen Xu, Shiyi Chen
Journal: Bioactive Materials (2024)

The rate of retear after surgical repair remains high. Mesenchymal stem cells (MSCs) have been extensively employed in regenerative medicine for several decades. However, safety and ethical concerns constrain their clinical application. Tendon Stem/Progenitor Cells (TSPCs)-derived exosomes have emerged as promising cell-free therapeutic agents. Therefore, urgent studies are needed to investigate whether TSPC-Exos could enhance tendon-bone healing and elucidate the underlying mechanisms. In this study, TSPC-Exos were found to promote the proliferation, migration, and expression of fibrogenesis markers in BMSCs. Furthermore, TSPC-Exos demonstrated an ability to suppress the polarization of M1 macrophages while promoting M2 macrophage polarization. In a rat model of rotator cuff repair, TSPC-Exos modulated inflammation and improved the histological structure of the tendon-bone interface, the biomechanical properties of the repaired tendon, and the function of the joint. Mechanistically, TSPC-Exos exhibited high expression of miR-21a-5p, which regulated the expression of PDCD4. The PDCD4/AKT/mTOR axis was implicated in the therapeutic effects of TSPC-Exos on proliferation, migration, and fibrogenesis in BMSCs. This study introduces a novel approach utilizing TSPC-Exos therapy as a promising strategy for cell-free therapies, potentially benefiting patients with rotator cuff tear in the future.
Disease-derived circulating extracellular vesicle preconditioning: A promising strategy for precision mesenchymal stem cell therapy
Authors: Ke Lv, Tian Wu, Shuyun Liu, Peng Lou, Pingya Zhou, Yizhuo Wang, Xiyue Zhou, Shu Zhang, Dan Du, Yanrong Lu, Meihua Wan, Jingping Liu
Journal: Acta Pharmaceutica Sinica B (2024)

Mesenchymal stem cell (MSC)-based therapies have emerged as promising methods for regenerative medicine; however, how to precisely enhance their tissue repair effects is still a major question in the field. Circulating extracellular vesicles (EVs) from diseased states carry diverse pathological information and affect the functions of recipient cells. Based on this unique property, we report that disease-derived circulating EV (disease-EV) preconditioning is a potent strategy for precisely enhancing the tissue repair potency of MSCs in diverse disease models. Briefly, plasma EVs from lung or kidney tissue injuries were shown to contain distinctly enriched molecules and were shown to induce tissue injury-specific gene expression responses in cultured MSCs. Disease-EV preconditioning improved the performance (including proliferation, migration, and growth factor production) of MSCs through metabolic reprogramming (such as
Pyroptosis: Induction and inhibition strategies for immunotherapy of diseases
Authors: Junjun Wu, Hong Wang, Pu Gao, Songying Ouyang
Journal: Acta Pharmaceutica Sinica B (2024)

Cell death is a central process for organismal health. Pyroptosis, namely pyroptotic cell death, is recognized as a critical type that disrupts membrane and triggers pro-inflammatory cytokine secretion
Paracetamol Combination Therapy for Back Pain and Osteoarthritis: A Systematic Review and Meta-Analyses
Authors: Zhiying Cao, Kaiyue Han, Hanting Lu, Sandalika Illangamudalige, Christina Abdel Shaheed, Lingxiao Chen, Andrew J. McLachlan, Asad E. Patanwala, Christopher G. Maher, Chung-Wei Christine Lin, Lyn March, Manuela L. Ferreira, Stephanie Mathieson
Journal: Drugs (2024)

Although paracetamol (acetaminophen) combined with other analgesics can reduce pain intensity in some pain conditions, its effectiveness in managing low back pain and osteoarthritis is unclear. This systematic review investigated whether paracetamol combination therapy is more effective and safer than monotherapy or placebo in low back pain and osteoarthritis.
The Role of <i>N</i>6-methyladenosine Modification in Gametogenesis and Embryogenesis: Impact on Fertility
Authors: Yujie Wang, Chen Yang, Hanxiao Sun, Hui Jiang, Pin Zhang, Yue Huang, Zhenran Liu, Yaru Yu, Zuying Xu, Huifen Xiang, Chengqi Yi
Journal: Genomics Proteomics & Bioinformatics (2024)

The most common epigenetic modification of messenger RNAs (mRNAs) is N6-methyladenosine (m6A), which is mainly located near the 3' untranslated region of mRNAs, near the stop codons, and within internal exons. The biological effect of m6A is dynamically modulated by methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers). By controlling post-transcriptional gene expression, m6A has a significant impact on numerous biological functions, including RNA transcription, translation, splicing, transport, and degradation. Hence, m6A influences various physiological and pathological processes, such as spermatogenesis, oogenesis, embryogenesis, placental function, and human reproductive system diseases. During gametogenesis and embryogenesis, genetic material undergoes significant changes, including epigenomic modifications such as m6A. From spermatogenesis and oogenesis to the formation of an oosperm and early embryogenesis, m6A changes occur at every step. m6A abnormalities can lead to gamete abnormalities, developmental delays, impaired fertilization, and maternal-to-zygotic transition blockage. Both mice and humans with abnormal m6A modifications exhibit impaired fertility. In this review, we discuss the dynamic biological effects of m6A and its regulators on gamete and embryonic development and review the possible mechanisms of infertility caused by m6A changes. We also discuss the drugs currently used to manipulate m6A and provide prospects for the prevention and treatment of infertility at the epigenetic level.
Incidence of peritoneal cancer after oophorectomy among <i>BRCA1</i> and <i>BRCA2</i> mutation carriers
Authors: Steven A Narod, Jacek Gronwald, Beth Karlan, Pal Moller, Tomasz Huzarski, Nadine Tung, Amber Aeilts, Andrea Eisen, Susan Randall Armel, Christian F Singer, William D Foulkes, Susan L Neuhausen, Olufunmilayo Olopade, Tuya Pal, Robert Fruscio, Kelly Metcalfe, Rebecca Raj, Michelle Jacobson, Ping Sun, Jan Lubinski, Joanne Kotsopoulos
Journal: JNCI Journal of the National Cancer Institute (2024)

To estimate the incidence of primary peritoneal cancer after preventive bilateral oophorectomy in women with a BRCA1 or BRCA2 mutation.
Enrichment of Rare Variants of Hemophagocytic Lymphohistiocytosis Genes in Systemic Juvenile Idiopathic Arthritis
Authors: Mariana Correia Marques, Danielle Rubin, Emily G. Shuldiner, Mallika Datta, Elizabeth Schmitz, Gustavo Gutierrez Cruz, Andrew Patt, Elizabeth Bennett, Alexei Grom, Dirk Foell, Marco Gattorno, John Bohnsack, Rae S. M. Yeung, Sampath Prahalad, Elizabeth Mellins, Jordi Anton, Claudio A. Len, Sheila Oliveira, Patricia Woo, Seza Ozen, Zuoming Deng, Michael J. Ombrello
Journal: Arthritis & Rheumatology (2024)

Our objective was to evaluate whether there is an enrichment of rare variants in familial hemophagocytic lymphohistiocytosis (HLH)-associated genes among patients with systemic juvenile idiopathic arthritis (sJIA) with or without macrophage activation syndrome (MAS).
Development and Initial Validation of the Novel Scleroderma Clinical Trials Consortium Activity Index
Authors: Laura Ross, Dylan Hansen, Susanna Proudman, Dinesh Khanna, Ariane L. Herrick, Wendy Stevens, Murray Baron, Mandana Nikpour
Journal: Arthritis & Rheumatology (2024)

Accurate measurement of disease activity in systemic sclerosis (SSc) remains a significant clinical challenge. The Scleroderma Clinical Trials Consortium (SCTC) convened an Activity Index (AI) Working Group (WG) to develop a novel measure of disease activity (SCTC-AI).
Hunting imaging biomarkers in pulmonary fibrosis: Benchmarks of the AIIB23 challenge
Authors: Yang Nan, Xiaodan Xing, Shiyi Wang, Zeyu Tang, Federico N Felder, Sheng Zhang, Roberta Eufrasia Ledda, Xiaoliu Ding, Ruiqi Yu, Weiping Liu, Feng Shi, Tianyang Sun, Zehong Cao, Minghui Zhang, Yun Gu, Hanxiao Zhang, Jian Gao, Pingyu Wang, Wen Tang, Pengxin Yu, Han Kang, Junqiang Chen, Xing Lu, Boyu Zhang, Michail Mamalakis, Francesco Prinzi, Gianluca Carlini, Lisa Cuneo, Abhirup Banerjee, Zhaohu Xing, Lei Zhu, Zacharia Mesbah, Dhruv Jain, Tsiry Mayet, Hongyu Yuan, Qing Lyu, Abdul Qayyum, Moona Mazher, Athol Wells, Simon LF Walsh, Guang Yang
Journal: Medical Image Analysis (2024)

Airway-related quantitative imaging biomarkers are crucial for examination, diagnosis, and prognosis in pulmonary diseases. However, the manual delineation of airway structures remains prohibitively time-consuming. While significant efforts have been made towards enhancing automatic airway modelling, current public-available datasets predominantly concentrate on lung diseases with moderate morphological variations. The intricate honeycombing patterns present in the lung tissues of fibrotic lung disease patients exacerbate the challenges, often leading to various prediction errors. To address this issue, the 'Airway-Informed Quantitative CT Imaging Biomarker for Fibrotic Lung Disease 2023' (AIIB23) competition was organized in conjunction with the official 2023 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI). The airway structures were meticulously annotated by three experienced radiologists. Competitors were encouraged to develop automatic airway segmentation models with high robustness and generalization abilities, followed by exploring the most correlated QIB of mortality prediction. A training set of 120 high-resolution computerised tomography (HRCT) scans were publicly released with expert annotations and mortality status. The online validation set incorporated 52 HRCT scans from patients with fibrotic lung disease and the offline test set included 140 cases from fibrosis and COVID-19 patients. The results have shown that the capacity of extracting airway trees from patients with fibrotic lung disease could be enhanced by introducing voxel-wise weighted general union loss and continuity loss. In addition to the competitive image biomarkers for mortality prediction, a strong airway-derived biomarker (Hazard ratio>1.5, p < 0.0001) was revealed for survival prognostication compared with existing clinical measurements, clinician assessment and AI-based biomarkers.
Prey Shifts Drive Venom Evolution in Cone Snails
Authors: Thomas Lund Koch, Samuel D Robinson, Paula Flórez Salcedo, Kevin Chase, Jason Biggs, Alexander E Fedosov, Mark Yandell, Baldomero M Olivera, Helena Safavi-Hemami
Journal: Molecular Biology and Evolution (2024)

Venom systems are complex traits that have independently emerged multiple times in diverse plant and animal phyla. Within each venomous lineage there typically exists interspecific variation in venom composition where several factors have been proposed as drivers of variation, including phylogeny and diet. Understanding these factors is of broad biological interest and has implications for the development of antivenom therapies and venom-based drug discovery. Because of their high species richness and the presence of several major evolutionary prey shifts, venomous marine cone snails (genus Conus) provide an ideal system to investigate drivers of interspecific venom variation. Here, by analyzing the venom gland expression profiles of ∼3,000 toxin genes from 42 species of cone snail, we elucidate the role of prey-specific selection pressures in shaping venom variation. By analyzing overall venom composition and individual toxin structures, we demonstrate that the shifts from vermivory to piscivory in Conus are complemented by distinct changes in venom composition independent of phylogeny. In vivo injections of venom from piscivorous cone snails in fish further showed a higher potency compared with venom of nonpiscivores demonstrating a selective advantage. Together, our findings provide compelling evidence for the role of prey shifts in directing the venom composition of cone snails and expand our understanding of the mechanisms of venom variation and diversification.
Selfing Promotes Spread and Introgression of Segregation Distorters in Hermaphroditic Plants
Authors: Hongru Wang, Léo Planche, Vladimir Shchur, Rasmus Nielsen
Journal: Molecular Biology and Evolution (2024)

Abstract Segregation distorters (SDs) are genetic elements that distort the Mendelian segregation ratio to favor their own transmission and are able to spread even when they incur fitness costs on organisms carrying them. Depending on the biology of the host organisms and the genetic architecture of the SDs, the population dynamics of SDs can be highly variable. Inbreeding is considered an effective mechanism for inhibiting the spread of SDs in populations, and can evolve as a defense mechanism against SDs in some systems. However, we show that inbreeding in the form of selfing in fact promotes the spread of SDs acting as pollen killers in a toxin–antidote system in hermaphroditic plants by two mechanisms: (i) By reducing the effective recombination rate between killer and antidote loci in the two-locus system and (ii) by increasing the proportion of SD alleles in individual flowers, rather than in the general gene-pool. We also show that in rice (Oryza sativa L.), a typical hermaphroditic plant, all molecularly characterized SDs associated with pollen killing were involved in population hybridization and have introgressed across different species. Paradoxically, these loci, which are associated with hybrid incompatibility and can be thought of as Bateson–Dobzhansky–Muller incompatibility loci are expected to reduce gene-flow between species, in fact cross species boundaries more frequently than random loci, and may act as important drivers of introgression.
Watch and wait in rectal cancer patients with residual mucin on magnetic resonance imaging following neoadjuvant therapy
Authors: Sean J Judge, Parisa Malekzadeh, Marina J Corines, Marc J Gollub, Natally Horvat, Mithat Gonen, Leonard Saltz, Andrea Cercek, Paul Romesser, Christopher Crane, Jinru Shia, Iris Wei, Maria Widmar, Emmanouil Pappou, Garrett M Nash, J Joshua Smith, Philip B Paty, Julio Garcia-Aguilar, Martin R Weiser
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Neoadjuvant therapy leads to a clinical complete response in a considerable proportion of patients with locally advanced rectal cancer, allowing for possible nonoperative management. The presence of mucin on magnetic resonance imaging (MRI) after neoadjuvant therapy leads to uncertainty about residual disease and appropriateness of a watch-and-wait strategy in patients with no evidence of disease on proctoscopy (endoscopic clinical complete response). Methods MRI reports for locally advanced rectal cancer patients seen between July 2016 and January 2020 at Memorial Sloan Kettering Cancer Center were queried for presence of mucin in the tumor bed on MRI following neoadjuvant therapy. Clinicodemographic, pathologic, and outcome data were compiled and analyzed. Results Of 71 patients with mucin on posttreatment MRI, 20 had a clinical complete response, and 51 had abnormalities on endoscopy and/or physical exam. One patient with a clinical complete response opted out of watch-and-wait; thus, 19 (27%) patients entered watch-and-wait, and 52 (73%) patients were planned for surgery (non–watch-and-wait). Of the 19 watch-and-wait patients, 15 (79%) have had no local regrowth with median follow-up of 50 months (range = 29-76 months), while 4 (21%) experienced regrowth between 9 and 29 months after neoadjuvant therapy. Of the 52 patients who were planned to have surgery (non–watch-and-wait), 49 underwent resection while 3 developed metastatic disease that precluded curative-intent surgery. Of the 49 patients who underwent surgery, 5 (10%) had a pathologic complete response (including the patient with an endoscopic clinical complete response). Conclusions The presence of mucin after neoadjuvant therapy for locally advanced rectal cancer does not preclude watch-and-wait management in otherwise appropriate candidates who achieve an endoscopic clinical complete response.
The risk and benefit profiles of US-eligible lung cancer screening attendees vs nonattendees
Authors: Elizabeth Y Zhang, Li C Cheung, Hormuzd A Katki, Barry I Graubard, Ahmedin Jemal, Anil K Chaturvedi, Rebecca Landy
Journal: JNCI Journal of the National Cancer Institute (2024)

The US Preventive Services Task Force (USPSTF) recommend lung cancer screening for individuals aged 50-80 years with at least 20 pack-years and no more than 15 quit-years, but uptake is low. The risk and benefit profiles of screening attendees are unknown; consequently, the impact and lost opportunity of ongoing lung cancer screening in the United States remains unclear.
Tadalafil for Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction: A Randomized Controlled Phase 3 Study
Authors: Marius M. Hoeper, Britta Oerke, Max Wissmüller, Hanno Leuchte, Christian Opitz, Michael Halank, Hans-Juergen Seyfarth, Stephan Baldus, Johann Bauersachs, Michael Böhm, Hossein-Ardeschir Ghofrani, Stavros Konstantinides, Karen M. Olsson, Rolf Wachter, Carolyn S.P. Lam, Behnaz Aminossadati, Stephan Rosenkranz
Journal: Circulation (2024)

We assessed the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension. In the double-blind PASSION study (Phosphodiesterase-5 Inhibition in Patients With Heart Failure With Preserved Ejection Fraction and Combined Post- and Pre-Capillary Pulmonary Hypertension), patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension were randomized 1:1 to receive tadalafil at a target dose of 40 mg or placebo. The primary end point was the time to the first composite event of adjudicated heart failure hospitalization or all-cause death. Secondary end points included all-cause mortality and improvements in New York Heart Association functional class or ≥10% improvement in 6-minute walking distance from baseline. Initially targeting 372 patients, the study was terminated early because of disruption in study medication supply. At that point, 125 patients had been randomized (placebo: 63; tadalafil: 62,). Combined primary end-point events occurred in 20 patients (32%) assigned to placebo and 17 patients (27%) assigned to tadalafil (hazard ratio, 1.02 [95% CI, 0.52-2.01]; P=0.95). There was a possible signal of higher all-cause mortality in the tadalafil group (hazard ratio, 5.10 [95% CI, 1.10-23.69]; P=0.04). No significant between-group differences were observed in other secondary end points. Serious adverse events occurred in 29 participants (48%) in the tadalafil group and 35 (56%) in the placebo group. The PASSION trial, terminated prematurely due to study medication supply disruption, does not support tadalafil use in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension, with potential safety concerns and no observed benefits in primary and secondary end points. URL: https://www.clinicaltrialsregister.eu/; Unique identifier: 2017-003688-37. URL: https://drks.de; Unique identifier: DRKS -DRKS00014595.
Rapid Adaptation and Interspecific Introgression in the North American Crop Pest <i>Helicoverpa zea</i>
Authors: Henry L North, Zhen Fu, Richard Metz, Matt A Stull, Charles D Johnson, Xanthe Shirley, Kate Crumley, Dominic Reisig, David L Kerns, Todd Gilligan, Tom Walsh, Chris D Jiggins, Gregory A Sword
Journal: Molecular Biology and Evolution (2024)

Insect crop pests threaten global food security. This threat is amplified through the spread of nonnative species and through adaptation of native pests to control measures. Adaptations such as pesticide resistance can result from selection on variation within a population, or through gene flow from another population. We investigate these processes in an economically important noctuid crop pest, Helicoverpa zea, which has evolved resistance to a wide range of pesticides. Its sister species Helicoverpa armigera, first detected as an invasive species in Brazil in 2013, introduced the pyrethroid-resistance gene CYP337B3 to South American H. zea via adaptive introgression. To understand whether this could contribute to pesticide resistance in North America, we sequenced 237 H. zea genomes across 10 sample sites. We report H. armigera introgression into the North American H. zea population. Two individuals sampled in Texas in 2019 carry H. armigera haplotypes in a 4 Mbp region containing CYP337B3. Next, we identify signatures of selection in the panmictic population of nonadmixed H. zea, identifying a selective sweep at a second cytochrome P450 gene: CYP333B3. We estimate that its derived allele conferred a ∼5% fitness advantage and show that this estimate explains independently observed rare nonsynonymous CYP333B3 mutations approaching fixation over a ∼20-year period. We also detect putative signatures of selection at a kinesin gene associated with Bt resistance. Overall, we document two mechanisms of rapid adaptation: the introduction of fitness-enhancing alleles through interspecific introgression, and selection on intraspecific variation.