tbuckley/cabot-search huggingface dataset:
Ongoing mpox outbreak in Kamituga, South Kivu province, associated with monkeypox virus of a novel Clade I sub-lineage, Democratic Republic of the Congo, 2024
Authors: Leandre Murhula Masirika, Jean Claude Udahemuka, Leonard Schuele, Pacifique Ndishimye, Saria Otani, Justin Bengehya Mbiribindi, Jean M. Marekani, Léandre Mutimbwa Mambo, Nadine Malyamungu Bubala, Marjan Boter, David F. Nieuwenhuijse, Trudie Lang, Ernest Balyahamwabo Kalalizi, Jean Pierre Musabyimana, Frank M. Aarestrup, Marion Koopmans, Bas B. Oude Munnink, Freddy Belesi Siangoli
Journal: Eurosurveillance (2024)

Since the beginning of 2023, the number of people with suspected monkeypox virus (MPXV) infection have sharply increased in the Democratic Republic of the Congo (DRC). We report near-to-complete MPXV genome sequences derived from six cases from the South Kivu province. Phylogenetic analyses reveal that the MPXV affecting the cases belongs to a novel Clade I sub-lineage. The outbreak strain genome lacks the target sequence of the probe and primers of a commonly used Clade I-specific real-time PCR.
Differences between first‐ and second‐generation autologous platelet concentrates
Authors: Elena Calciolari, Marina Dourou, Aliye Akcali, Nikolaos Donos
Journal: Periodontology 2000 (2024)

Abstract Autologous platelet concentrates (APCs) applied alone or combined with other biomaterials are popular bioactive factors employed in regenerative medicine. The main biological rationale of using such products is to concentrate blood‐derived growth factors and cells into the wound microenvironment to enhance the body's natural healing capacity. First‐generation APC is represented by platelet‐rich plasma (PRP). While different protocols have been documented for PRP preparation, they overall consist of two cycles of centrifugation and have important limitations related to the use of an anticoagulant first and an activator afterward, which may interfere with the natural healing process and the release of bioactive molecules. The second generation of platelet concentrates is represented by leukocyte and platelet‐rich fibrin (L‐PRF). L‐PRF protocols involve a single centrifugation cycle and do not require the use of anticoagulants and activators, which makes the preparation more straight forward, less expensive, and eliminates potential risks associated with the use of activators. However, since no anticoagulant is employed, blood undergoes rapid clotting within the blood collection tube; hence, a timely management of L‐PRF is crucial. This review provides an overview on the most documented protocols for APC preparations and critically discusses the main differences between first‐ and second‐generation APCs in terms of cell content, protein release, and the formation of a 3D fibrin network. It appears evident that the inconsistency in reporting protocol parameters by most studies has contributed to conflicting conclusions regarding the efficacy of different APC formulations and has significantly limited the ability to interpret the results of individual clinical studies. In the future, the use of a standardized classification system, together with a detailed reporting on APC protocol parameters is warranted to make study outcomes comparable. This will also allow to clarify important aspects on the mechanism of action of APCs (like the role of leukocytes and centrifugation parameters) and to optimize the use of APCs in regenerative medicine.
Small Extracellular Vesicles From Infarcted and Failing Heart Accelerate Tumor Growth
Authors: Tal Caller, Itai Rotem, Olga Shaihov-Teper, Daria Lendengolts, Yeshai Schary, Ruty Shai, Efrat Glick-Saar, Dan Dominissini, Menachem Motiei, Idan Katzir, Rachela Popovtzer, Merav Nahmoud, Alex Boomgarden, Crislyn D’Souza-Schorey, Nili Naftali-Shani, Jonathan Leor
Journal: Circulation (2024)

Myocardial infarction (MI) and heart failure are associated with an increased incidence of cancer. However, the mechanism is complex and unclear. Here, we aimed to test our hypothesis that cardiac small extracellular vesicles (sEVs), particularly cardiac mesenchymal stromal cell-derived sEVs (cMSC-sEVs), contribute to the link between post-MI left ventricular dysfunction (LVD) and cancer.
Single-domain antibodies as therapeutics for solid tumor treatment
Authors: Mingkai Wang, Tianlei Ying, Yanling Wu
Journal: Acta Pharmaceutica Sinica B (2024)

Single-domain antibodies (sdAbs), initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs, have emerged as a promising alternative to conventional therapeutic antibodies. These sdAbs have many superior physicochemical and pharmacological properties, including small size, good solubility and thermostability, easier accessible epitopes, and strong tissue penetration. However, the inherent challenges associated with the animal origin of sdAbs limit their clinical use. In recent years, various innovative humanization technologies, including complementarity-determining region (CDR) grafting or complete engineering of fully human sdAbs, have been developed to mitigate potential immunogenicity issues and enhance their compatibility. This review provides a comprehensive exploration of sdAbs, emphasizing their distinctive features and the progress in humanization methodologies. In addition, we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment, such as sdAb-drug conjugates, multispecific sdAbs, sdAb-based delivery systems, and sdAb-based cell therapy.
Repurposing disulfiram with CuET nanocrystals: Enhancing anti-pyroptotic effect through NLRP3 inflammasome inhibition for treating inflammatory bowel diseases
Authors: Xueming Xu, Yuanfeng Han, Jiali Deng, Shengfeng Wang, Shijie Zhuo, Kai Zhao, Wenhu Zhou
Journal: Acta Pharmaceutica Sinica B (2024)

Drug repurposing offers a valuable strategy for identifying new therapeutic applications for existing drugs. Recently, disulfiram (DSF), a drug primarily used for alcohol addiction treatment, has emerged as a potential treatment for inflammatory diseases by inhibiting pyroptosis, a form of programmed cell death. The therapeutic activity of DSF can be further enhanced by the presence of Cu
Microenvironment-responsive metal-phenolic network release platform with ROS scavenging, anti-pyroptosis, and ECM regeneration for intervertebral disc degeneration
Authors: Hao Zhou, Jinpeng He, Renfeng Liu, Jun Cheng, Yuhao Yuan, Wanpu Mao, Jun Zhou, Honghui He, Qianqi Liu, Wei Tan, Cijun Shuai, Youwen Deng
Journal: Bioactive Materials (2024)

Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, and extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD. In this study, we developed a multifunctional and microenvironment-responsive metal-phenolic network release platform, termed TMP@Alg-PBA/PVA, which could treat (IL-1β)-induced IVDD. The metal-phenolic network (TA-Mn-PVP, TMP) released from this platform targeted mitochondria to efficiently scavenge ROS and reduce ECM degradation. Pyroptosis was suppressed through the inhibition of the IL-17/ERK signaling pathway. These findings demonstrate the versatility of the platform. And in a rat model of IVDD, TMP@Alg-PBA/PVA exhibited excellent therapeutic effects by reducing the progression of the disease. TMP@Alg-PBA/PVA, therefore, presents clinical potential for the treatment of IVDD.
Retraction: Cancer-Associated PP2A Aα Subunits Induce Functional Haploinsufficiency and Tumorigenicity
Authors: Wen Chen, Jason D. Arroyo, Jamie C. Timmons, Richard Possemato, William C. Hahn
Journal: Cancer Research (2024)

In Fig. 2A, the same image appears to have been used to represent the B56d bands in lanes 5 and 6.In addition, the images of the B55a bands in lanes 4 and 6 appear to be the same. *The same image appears to have been used in Fig. 3C to represent the B55a band in lane 2 and in Fig. 1A to represent a distinct sample for B56a in lane 2 of the IP: FLAG panel.* In Fig. 4D, the same image seems to have been used to represent: * B55a in lanes 4, 5, and 9 and in lanes 6 and 10. * B56g in lanes 2 and 6 and in lanes 8 and 10. * B56e in lanes 1, 3, 6, and 7, in lanes 2 and 8, and in lanes 4, 5, and 9. * Ca in lanes 4 and 6. * In Fig. 5A, the same image seems to have been used to represent: * Aa in lanes 2, 3, and 5 in the right-hand panel.* B56g in lanes 1 and 4 in the left-hand panel, in lanes 1 and 2 of the right-hand panel, and in lanes 4 and 5 of the right-hand panel.* B56e in lanes 4 and 5 of the left-hand panel.* Ca in lanes 1, 2, and 3 of the right-hand panel.* In Fig. 5B, the same image seems to have been used to represent: * B55a in lanes 4 and 5 of the right-hand panel.* B56a in lanes 3 and 4 of the left-hand panel.* B56e in lanes 1 and 3 of the left-hand panel and in lanes 4 and 5 of the right-hand panel.* B56d in lanes 2, 5, and 6 of the left-hand panel and in lanes 3 and 4 of the righthand panel.* Ca in lanes 1 and 3 of the left-hand panel and in lanes 4 and 5 of the right-hand panel.* Aa in lanes 2, 3, and 4 of the right-hand panel.* In Fig. 6, the image used to represent MAPK in lanes 3 to 6 in the left-hand panel appears to be the same as the image used to represent MAPK in lanes 1 to 4 in the right-hand panel.
Retraction: Cytokines Modulate Telomerase Activity in a Human Multiple Myeloma Cell Line
Authors: Masaharu Akiyama, Teru Hideshima, Toshiaki Hayashi, Yu-Tzu Tai, Constantine S. Mitsiades, Nicholas Mitsiades, Dharminder Chauhan, Paul Richardson, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Cancer Research (2024)

This article (1) has been retracted at the request of the authors.There are concerns about the reliability of certain data arising from errors in the assembly of Figs. 2, 4, 5, 6, and 7.The image used to represent b-actin in lanes 5 and 6 in Fig. 2A was also used to represent hTERT mRNA in lanes 4 and 5 in Fig. 4B.The image used to represent b-actin in lanes 1 and 2 in Fig. 4B was also used to represent b-actin in distinct samples and treatments in both Fig. 6A (MM.1S/Dex group) in lanes 3 and 4 and Fig. 7B (right-hand panel) in lanes 3 and 4. The image used to represent b-actin in lanes 1 and 2 in Fig. 6A (MM.1S/Dex group) was also used to represent b-actin bands in distinct samples and treatments in Fig. 7B (right-hand panel) lanes 1 and 2. The image used to represent b-actin in lanes 5-9 in Fig. 4B was also used to represent b-actin bands in distinct samples and treatments in Fig. 7B in lanes 1-5 (left-hand panel).The same image was used to represent hTERT protein in distinct samples in lanes 2 and 6 of Fig. 5C.
AKTing on R Loops Makes for an ATRactive Target in Ovarian Cancer Therapy
Authors: Vijayalalitha Ramanarayanan, Philipp Oberdoerffer
Journal: Cancer Research (2024)

Abstract High-grade serous ovarian carcinoma (HGSOC) is the deadliest subtype of ovarian cancer. While PARP inhibitors (PARPi) have transformed the care of advanced HGSOC, PARPi resistance poses a major limitation to their clinical utility. DNA damage checkpoint signaling via ATR kinase can counteract PARPi-induced replication stress, making ATR an attractive therapeutic target in PARPi-resistant tumors. However, ATR inhibitor (ATRi) efficacy in the clinic is low, emphasizing the need for suitable combination treatments. In this issue of Cancer Research, Huang and colleagues uncovered cytotoxic synergism between inhibition of the PI3K/AKT pathway and ATR based on high-throughput screening for ATRi drug combinations in PARPi-resistant HGSOC cells. Dual inhibition of ATR and AKT resulted in aberrant replication stress and cell death, which was attributed in part to impaired resolution of replication-stalling RNA:DNA hybrids (R loops). The authors identified the DNA/RNA helicase DHX9 as a clinically relevant candidate effector of R loop resolution in HGSOC. AKT interacted with and recruited DHX9 to R loops, where it complemented ATR in facilitating their removal. Underlining the therapeutic potential relevance of these findings, combined inhibition of ATR and AKT caused near complete tumor regression in HGSOC xenograft models, and elevated AKT/DHX9 levels correlated with poor survival in patients with HGSOC. Of note, the genotoxic consequences of dual ATRi/AKTi treatment extended beyond PARPi-resistant tumors and are likely to affect genome integrity beyond R loops. The work by Huang and colleagues thus provides compelling rationale for the exploration of combined targeting of the AKT and ATR pathways as a potentially broadly applicable treatment of advanced HGSOC. See related article by Huang et al., p. 887
Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma
Authors: Jiwon Hong, Jung Woo Eun, Geum Ok Baek, Jae Youn Cheong, Seryoung Park, Soon Sun Kim, Hyo Jung Cho, Su Bin Lim
Journal: Clinical and Molecular Hepatology (2024)

Background/Aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Despite identification of several biomarkers for HCC diagnosis, challenges such as low sensitivity and intratumoral heterogeneity have impeded early detection, highlighting the need for etiology-specific blood biomarkers.Methods: We generated whole-transcriptome sequencing (WTS) and targeted proteome data from buffy coat and plasma samples from HCC patients. By integrating etiological information on viral infection, we investigated the etiology-specific gene expression landscape at the blood level. Validation of differentially expressed genes (DEGs) was performed using publicly available RNA-seq datasets and qRT‒PCR with AUC analyses.Results: Differential expression analyses with multiomics data revealed distinct gene expression profiles between HBV-associated HCC and nonviral HCC, indicating the presence of etiology-specific blood biomarkers. The identified DEGs were validated across multiple independent datasets, underscoring their utility as biomarkers. Additionally, single-cell RNA-seq analysis of HCC confirmed differences in DEG expression across distinct immune cell types.Conclusions: Our buffy coat WTS data and plasma proteome data may serve as reliable sources for identifying etiology-specific blood biomarkers of HCC and might contribute to discovery of therapeutic targets for HCC across different etiologies.
Pyloric-directed therapy for gastroparesis: to cut or to relax?
Authors: Linda Zhang, Mouen A. Khashab
Journal: Endoscopy (2024)

In this issue of Endoscopy, Gonzalez et al. present the first double-blind randomized controlled trial to compare the efficacy of gastric peroral endoscopic myotomy (G-POEM) versus botulinum toxin injection (BTI) for the treatment of refractory gastroparesis [1]. Gastric peroral endoscopic myotomy (G-POEM) was first introduced in 2013 as an alternative option for patients with refractory gastroparesis [2]. Recently, two clinical trials, a large multicenter prospective trial by Vosoughi et al. [3] and a randomized sham-controlled trial by Martinek et al. [4], have evaluated the use of G-POEM in refractory gastroparesis and demonstrated a clinical success rate of 56%–70% at 12 months, with low rates of adverse events. Despite these promising results, G-POEM remains a technically challenging procedure, available only in expert centers, while BTI is widely available. Previously no study had directly compared the two endoscopic pylorus-directed therapies.
Management Consensus Guidelines for Hepatocellular Carcinoma: 2023 Update on Surveillance, Diagnosis, Systemic Treatment, and Posttreatment Monitoring by the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan
Authors: Wei Teng, Hung-Wei Wang, Shi-Ming Lin
Journal: Liver Cancer (2024)

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan established HCC management consensus guidelines in 2016 and updated them in 2023. Current recommendations focus on addressing critical issues in HCC management, including surveillance, diagnosis, systemic treatment, and posttreatment monitoring. For surveillance and diagnosis, we updated the guidelines to include the role of protein induced by vitamin K absence or antagonist II (PIVKA-II) and gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in detecting HCCs. For systemic treatment, the updated guidelines summarize the multiple choices available for targeted therapy, immune checkpoint inhibitors, and a combination of both, especially for those carcinomas refractory to or unsuitable for transarterial chemoembolization. We have added a new section, posttreatment monitoring, that describes the important roles of PIVKA-II and EOB-MRI after HCC therapy, including surgery, locoregional therapy, and systemic treatment. Through this update of the management consensus guidelines, patients with HCC may benefit from optimal diagnosis, therapeutic modalities, and posttreatment monitoring.
When I use a word . . . Medicines regulation—penicillin
Authors: Jeffrey K Aronson
Journal: BMJ (2024)

Penicillin has a history that antedates its discovery by Alexander Fleming in London and its isolation and purification by Howard Florey, Ernst Chain, and Norman Heatley in Oxford. Before that it had been used as a raw broth of <i>Penicillium</i> organisms in local treatment of infections such as furuncles and conjunctivitis. After its introduction for parenteral administration and its manufacture in the USA during the second world war, shortage led to its being misused in dilute solutions, as described in Graham Greene's film treatment for Carol Reed's film <i>The Third Man</i> (1949), later published as a novella. The use of penicillin in the UK during the war had been governed by the Control of Penicillin Order No. 731, established under the Defence Regulations, a set of wartime emergency regulations, promulgated under the Emergency Powers (Defence) Act 1939. The order made its sale a criminal offence, unless it had been prescribed by a doctor. In 1947, largely because of concern about the emergence of resistant organisms through the use of low doses and the marketing of many types of non-parenteral formulations, the Penicillin Order was replaced by the Penicillin Act, which restricted the sale and supply of penicillin to duly qualified medical practitioners, registered dental practitioners, or registered veterinary surgeons, and to registered pharmacists or authorised sellers of poisons.
Physician associates: Doctors express anger over RCP extraordinary general meeting
Authors: Abi Rimmer
Journal: BMJ (2024)

Doctors have expressed concerns over the way a meeting at the Royal College of Physicians to discuss issues related to physician associates was conducted. On 13 March the college held an extraordinary general meeting (EGM) to discuss growing concerns among its members and fellows about physician associates (PAs). The college has hosted the Faculty of Physician Associates, the professional membership body for the UK's PAs, since 2015. During the meeting RCP president Sarah Clarke chaired a debate on five motions (box 1) covering PAs' scope of practice, accountability, evaluation, impact on training opportunities, and pace and scale of rollout. RCP fellows have until Wednesday 20 March to vote in a ballot on the motions. Box 1 ### Motions debated at RCP extraordinary general meeting10 #### 1. Scope of practice Physician associates are not doctors. They should not be regarded as replacements for doctors, and they should never replace a doctor on a rota. They are valued healthcare professionals who participate in patient care in addition to the rest of the wider multidisciplinary team. #### 2. Accountability This EGM notes the current legal restrictions on who can prescribe medication or request ionising radiation and reminds all medically qualified membership categories of the college that they remain responsible for any such decisions by others that they may be asked to endorse. #### 3. Evaluation This EGM calls on the RCP to contribute actively to generating an evidence base and evaluation framework around the introduction of PAs, addressing (for example) clinical outcomes, cost effectiveness, safety, the patient experience, staff wellbeing and interrelationships, and implications for the healthcare workforce. … RETURN TO TEXT
Deep learning-assisted detection and segmentation of intracranial hemorrhage in noncontrast computed tomography scans of acute stroke patients: a systematic review and meta-analysis
Authors: Ping Hu, Tengfeng Yan, Bing Xiao, Hongxin Shu, Yilei Sheng, Yanze Wu, Lei Shu, Shigang Lv, Minhua Ye, Yanyan Gong, Miaojing Wu, Xingen Zhu
Journal: International Journal of Surgery (2024)

Deep learning (DL)-assisted detection and segmentation of intracranial hemorrhage stroke in noncontrast computed tomography (NCCT) scans are well-established, but evidence on this topic is lacking.
Machine learning based peri-surgical risk calculator for abdominal related emergency general surgery: a multicenter retrospective study
Authors: Biao Chen, Weiyong Sheng, Zhixin Wu, Bingqing Ma, Nan Cao, Xushu Li, Jia Yang, Xiaowei Yuan, Lizhao Yan, Gaobo Zhu, Yuanhong Zhou, Zhonghua Huang, Meiwei Zhu, Xuehui Ding, Hansong Du, Yanqing Wan, Xuan Gao, Xing Cheng, Peng Xu, Teng Zhang, Kaixiong Tao, Xiaoming Shuai, Ping Cheng, Yong Gao, Jinxiang Zhang
Journal: International Journal of Surgery (2024)

Currently, there is a lack of ideal risk prediction tools in the field of emergency general surgery (EGS). The American Association for the Surgery of Trauma recommends developing risk assessment tools specifically for EGS-related diseases. In this study, we sought to utilize machine learning (ML) algorithms to explore and develop a web-based calculator for predicting five perioperative risk events of eight common operations in EGS.