Browse Articles
Discover research articles across all indexed journals
NMR Structural Characterization of SARS-CoV-2 ORF6 Reveals an N-Terminal Membrane Anchor
Tracing the spatial origins and spread of SARS-CoV-2 Omicron lineages in South Africa
Risk and prognosis of second primary malignancies in patients with follicular lymphoma in the era of rituximab: A population study based on the SEER database
Objective Follicular lymphoma (FL) patients have achieved favorable long-term survival since the introduction of rituximab. However, the development of second primary malignancies (SPMs) indicates a poor survival prognosis for FL patients, and large-scale studies in this field remain limited. This study investigates the prognostic factors for FL patients in the rituximab era, as well as the clinical characteristics, risk factors, and prognosis for patients who developed SPMs. Methods From 2000 to 2020, a total of 33,104 patients with pathologically confirmed FL were identified within the Surveillance, Epidemiology, and End Results (SEER) database. Competing-risk regression analysis was used to assess prognostic factors for lymphoma-specific survival (LSS), risk factors for developing SPMs, and prognosis in FL patients. Results Multivariate analysis identified age ≥ 40 years, Black race, unmarried status, non-urban residence, nodal lymphoma presentation, Grade 3 histology, advanced Ann Arbor stage, and B symptoms as independent adverse prognostic factors for both overall survival (OS) and LSS. Chemotherapy as initial treatment was associated with inferior LSS in FL patients. Protective factors for OS and LSS included female sex, higher income, diagnosis post-2005, diagnosis-to-treatment intervals >1 month, and receipt of radiotherapy or surgery. SPMs correlated with reduced LSS risk in FL patients. Elevated SPM incidence among patients aged>40years, and non-Hispanic ethnicity, while reduced SPM risks were observed in females, unmarried patients, those receiving non-radiotherapy initial treatment, Grade 3 cases, and patients diagnosed during 2015–2019. Notably, FL patients aged >60 years, unmarried, and those diagnosed post-2010 demonstrated heightened OS risk following SPM development. Conversely, initial radiotherapy conferred protective effects against both OS and LSS in patients with SPMs. Conclusion In this study, we conducted a large, population-based analysis across the United States to identify risk factors for the development of SPMs and to delineate prognostic indicators for FL patients in the context of rituximab therapy, along with the clinical characteristics, risk factors, and prognostic features associated with SPMs. These findings have translational implications for risk-adapted surveillance. Future studies should validate predictive models across diverse healthcare settings, elucidate molecular mechanisms of SPM pathogenesis in FL, and evaluate targeted screening interventions through prospective trials.
Homochiral versus Racemic 2D Covalent Organic Frameworks
BH3 mimetics targeting BCL-XL have efficacy in solid tumors with RB1 loss and replication stress
Abstract BH3 mimetic drugs that inhibit BCL-2, BCL-XL, or MCL-1 have limited activity in solid tumors. Through assessment of xenograft-derived 3D prostate cancer models and cell lines we find that tumors with RB1 loss are sensitive to BCL-XL inhibition. In parallel, drug screening demonstrates that disruption of nucleotide pools by agents including thymidylate synthase inhibitors sensitizes to BCL-XL inhibition, together indicating that replication stress increases dependence on BCL-XL. Mechanistically we establish that replication stress sensitizes to BCL-XL inhibition through TP53/CDKN1A-dependent suppression of BIRC5 expression. Therapy with a BCL-2/BCL-XL inhibitor (navitoclax) in combination with thymidylate synthase inhibitors (raltitrexed or capecitabine) causes marked and prolonged tumor regression in prostate and breast cancer xenograft models. These findings indicate that BCL-XL inhibitors may be effective as single agents in a subset of solid tumors with RB1 loss, and that pharmacological induction of replication stress may be a broadly applicable approach for sensitizing to BCL-XL inhibitors.
Experiences, views and perceptions of recovery following musculoskeletal trauma of patients and physiotherapists: a qualitative study
The aim of this qualitative phenomenology study using two methods (semi-structured interviews, focus groups), was to explore patients’ and physiotherapists’ views and perceptions of recovery, and what constitutes successful recovery following musculoskeletal trauma within the early stages of recovery. Participants were recruited from one major trauma centre in the United Kingdom and data collected via Microsoft Teams, or via a telephone call. Inclusion criteria for patient interviews: purposive sample of adults (≥18 years) who sustained a traumatic musculoskeletal injury, admitted as an inpatient within 4 weeks of injury, mental capacity, and able to communicate in English. Purposive sampling included age, gender, and injury characteristics. Focus group inclusion criteria: physiotherapists with experience managing patients with musculoskeletal trauma. Interviews and focus groups were informed by an evidenced based topic guide, audio recorded and transcribed verbatim. Trustworthiness of the data was strengthened using multiple strategies, e.g., member checking. Interpretative Phenomenological Analysis was used for the patient interviews and the Kreuger Framework for the focus groups. Participants included 17 patient interviews and 10 physiotherapists in two focus groups. Three themes emerged from patient interviews: understanding and impact of the accident and injuries, the early stages of recovery and physiotherapy, and healthcare and setting influences. Eight themes emerged from the focus groups: process of recovery, what is being fully recovered, it’s more than just communicating with the patient, psychological impact of trauma affecting recovery, system influences/resources for recovery, influencers to recovery, barriers to using patient reported outcome measures to evaluate recovery, and what actually is useful to measure in trauma? Recovery following musculoskeletal trauma is complex, individual and focused on returning to ‘normal’. Similarities across patient and physiotherapist views of recovery exist. Differences between participant groups were evident, centred on communication and what is important to the patient in their recovery.
A Chiral CdS Magic-Size Cluster with Enantiomerically-Biased Crystallization
Searching for dark matter with a spin-based interferometer
Abstract Axion-like particles (ALPs) arise from well-motivated extensions to the Standard Model and could account for dark matter. ALP dark matter would manifest as a field oscillating at an (as of yet) unknown frequency. The frequency depends linearly on the ALP mass and plausibly ranges from 10−22 to 10 eV/c 2. This motivates broadband search approaches. We report on a direct search for ALP dark matter with an interferometer composed of two atomic K-Rb-3He comagnetometers, one situated in Mainz, Germany, and the other in Kraków, Poland. We leverage the anticipated spatio-temporal coherence properties of the ALP field and probe all ALP-gradient-spin interactions covering a mass range of nine orders of magnitude. No significant evidence of an ALP signal is found. We thus place new upper limits on the ALP-neutron, ALP-proton and ALP-electron couplings reaching below g a N N < 10−9 GeV−1, g a P P < 10−7 GeV−1 and g a e e < 10−6 GeV−1, respectively. These limits improve upon previous laboratory constraints for neutron and proton couplings by up to three orders of magnitude.
Effect of biologic treatments on growth in children with juvenile idiopathic arthritis: A systematic review
Children with Juvenile idiopathic arthritis (JIA) often experience growth retardation due to various factors. The advent of biologic therapies has revolutionized the management of aggressive forms of JIA. This systematic review aims to provide updated insights into the impact of biologic treatments on growth retardation in pediatric JIA patients. Following PRISMA guidelines, we systematically searched Medline, Embase, and the Cochrane Library for eligible articles. Included were cohort studies, trials, and retrospective studies that evaluated growth outcomes in children with JIA receiving biologic therapy. Twelve studies published between 2003 and 2018 were analyzed, encompassing 1513 patients with a mean age of 11.4 years. Tumor necrosis factor alpha inhibitors were the predominant biologic agents used (75.8%), with a mean follow-up duration of 2 years post-biologic therapy initiation. Growth assessment criteria included Height Standard-deviation-score (HSDS), growth velocity, and height velocity (cm/year). Before biologic treatment, 15% of patients exhibited growth delay, while 75.4% had impaired growth. Following biologic therapy, growth delay decreased to 8% and impaired growth to 36.8%. Patients with systemic JIA showed lower changes in growth parameters compared to others, and no significant differences were observed between different biologic drugs. However, lower growth velocity changes were noted in patients treated with multiple biologic agents. Two studies suggested that growth catch-up was most pronounced during the first year of treatment. This systematic review highlights the potential of biologic therapies in mitigating growth impairment associated with JIA. Despite observed positive effects, further research is warranted to elucidate underlying mechanisms and optimize treatment strategies.
Template-Directed Synthesis of Recognition-Encoded Melamine Oligomers Using a Base-Filling Strategy
Divergent molecular pathways govern temperature-dependent wheat stem rust resistance genes
Abstract The wheat stem rust pathogen Puccinia graminis f. sp. tritici ( Pgt ) causes severe crop losses worldwide. Several stem rust resistance ( Sr ) genes exhibit temperature-dependent immune responses. Sr6 -mediated resistance is enhanced at lower temperatures, whereas Sr13 and Sr21 resistances are enhanced at higher temperatures. Here, we clone Sr6 using mutagenesis and resistance gene enrichment and sequencing (MutRenSeq), identifying it to encode a nucleotide-binding leucine-rich repeat (NLR) protein with an integrated BED domain. Sr6 temperature sensitivity is also transferred to wheat plants transformed with the Sr6 gene. Differential gene expression analysis of near-isogenic lines inoculated with Pgt at varying temperatures reveals that genes upregulated in the low-temperature-effective Sr6 response differ from those upregulated in the high-temperature-effective responses associated with Sr13 and Sr21 . These findings highlight divergent molecular pathways involved in temperature-sensitive immunity and inform future strategies for deployment and engineering of genetic resistance in response to a changing climate.
BGM-YOLO: An accurate and efficient detector for detecting plant disease
Given the complexity of crop growth environments in nature, where leaf backgrounds often include soil, weeds, and other plants, along with variable lighting conditions, and considering the small size of leaf spots and the wide variety of crop diseases with significant scale differences, this paper proposes a new BGM-YOLO model structure aimed at improving accuracy and inference speed. First, the GSBottleneck module is utilized to enhance the C2f module of the YOLOv8n model, leading to the introduction of the GSC2f module, which reduces computational costs and increases inference efficiency. Next, the model incorporates a multiscale bitemporal fusion module (BFM) to increase the effectiveness and robustness of feature fusion across different levels. Finally, we developed a median-enhanced spatial and channel attention block (MECS) that combines both channel and spatial attention mechanisms, effectively improving the capture and fusion of small-scale features. The experimental results demonstrate that the BGM-YOLO model achieves a 3.9% improvement in the mean average precision (mAP) over the original model. In crop disease detection tasks, the BGM-YOLO model has higher detection accuracy and a lower false negative rate, confirming its practical value in complex application scenarios.
Mechanism of Giant Magnetic Field Effect in a Red Fluorescent Protein
Estimating small area population from health intervention campaign surveys and partially observed settlement data
Abstract Effective governance requires timely and reliable small area population counts. Geospatial modelling approaches which utilise bespoke microcensus surveys and satellite-derived settlement maps and other spatial datasets have been developed to fill population data gaps in countries where censuses are outdated and incomplete. However, logistics and costs of microcensus surveys and tree canopy or cloud cover obscuring settlements in satellite images limit its wider applications in tropical rural settings. Here, we present a two-step Bayesian hierarchical modelling approach that can integrate routinely collected health intervention campaign data and partially observed settlement data to produce reliable small area population estimates. Reductions in relative error rates were 32–73% in a simulation study, and ~32% when applied to malaria survey data in Papua New Guinea. The results highlight the value of demographic data routinely collected through health intervention campaigns or household surveys for improving small area population estimates, and how biases introduced by satellite data limitations can be overcome.