Proc Natl Acad Sci U S A
January 2025
The effects of T cell differentiation arising from immune checkpoint inhibition targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on the immunological memory response remain unclear. Our investigation into the effects of anti-CTLA-4 and anti-PD-1 on memory T cell formation in mice reveals that memory T cells generated by anti-CTLA-4 exhibit greater expansion, cytokine production, and antitumor activity than those from anti-PD-1. Notably, anti-CTLA-4 preserves more T cell factor-1 (TCF-1)+ T cells during priming, while anti-PD-1 leads to more thymocyte selection-associated high mobility group box (TOX)+ T cells.
View Article and Find Full Text PDFThe emergence of parasites partially resistant to artemisinins (ART-R) poses a significant threat to recent gains in malaria control. ART-R has been associated with PfKelch13 (K13) mutations, which differ in fitness costs. This study investigates the gametocyte production and transmission fitness of African and Asian isolates with different K13 genotypes across multiple mosquito species.
View Article and Find Full Text PDFAmyloidogenic protein aggregation is a pathological hallmark of Alzheimer's Disease (AD). As such, this critical feature of the disease has been instrumental in guiding research on the mechanistic basis of disease, diagnostic biomarkers and preventative and therapeutic treatments. Here we review identified molecular triggers and modulators of aggregation for two of the proteins associated with AD: amyloid beta and tau.
View Article and Find Full Text PDFAlthough the sternoclavicular joint shares structural similarities with the knee and hip joints as a diarthrodial joint, its biomechanics differ significantly due to its non-weight-bearing nature. Nevertheless, it is subject to considerable loading, leading to increased susceptibility to osteoarthritis, a prevalent condition characterized by the degeneration of the joint's articular surfaces and fibrocartilaginous intra-articular disc. The osteoarthritic degeneration of the fibrocartilaginous and cartilaginous surfaces of the sternoclavicular joint has been investigated, considering multiple factors.
View Article and Find Full Text PDFIntroduction: Alcohol consumption is a global health issue linked to over 200 diseases and accounts for 5.3% of all deaths annually. We aimed to determine the sociodemographic factors associated with alcohol consumption among Cambodian women and men aged 15-49 years.
View Article and Find Full Text PDFIntraductal papillary mucinous neoplasms (IPMN) are commonly detected pancreatic cysts that may transform into pancreatic ductal adenocarcinoma (PDAC). Predicting which IPMNs will progress to PDAC remains a clinical challenge. Moreover, identifying those clinically evident IPMNs for which a surveillance approach is best is a dire clinical need.
View Article and Find Full Text PDFBackground: Piperaquine, used in combination with dihydroartemisinin, has been identified as a promising partner drug for uncomplicated treatment and chemoprevention of Plasmodium falciparum malaria in Africa. In light of the earlier spread of piperaquine resistance in Southeast Asia, mediated primarily by mutations in the drug efflux transporter PfCRT, we have explored whether PfCRT mutations would represent a probable path to piperaquine resistance becoming established in Africa.
Methods: We edited PfCRT mutations known to mediate piperaquine resistance in Southeast Asia into P.
Whole genome sequencing-based methodologies have become extremely relevant for the molecular surveillance of human pathogens and are being increasingly introduced into national reference laboratory services. In this study, we describe the validation and implementation of core-genome Multi-Locus Sequence Typing (cgMLST) and whole genome single-nucleotide polymorphism (wgSNP) analysis at the Irish Mycobacteria Reference Laboratory, as a replacement for Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) typing. Concordance of clustering, discriminatory power, and ease-of-use of both WGS analytical methods were evaluated.
View Article and Find Full Text PDFAccording to global regulations on hazardous chemicals, numerous alternatives have been manufactured and used in various consumer products. Suspect and non-target analyses are advanced analytical techniques used for identifying novel contaminants. In the present study, suspect and non-target analytical approaches using a gas chromatography coupled to a time-of-flight mass spectrometer were applied to identify novel contaminants in 40 pooled serum samples from a sub-population (n = 400) of the 2015-2017 national biomonitoring program.
View Article and Find Full Text PDFPhthalates and bisphenols (BPs) are well-known endocrine disrupting chemicals (EDCs) that are widely used in diverse consumer and personal care products. Despite their vulnerability, children are frequently exposed to phthalates and BPs in their surrounding environments. Although pre-school children spend most of their time in kindergarten, no comprehensive assessment of children' exposure to EDCs has been conducted according to the type of kindergarten.
View Article and Find Full Text PDF: Temperature-sensitive (TS) mutants of TP53 are thermally unstable, unfolded, and inactive at body temperature but can be refolded and reactivated at sub-physiological temperatures. TS TP53 may be amenable for functional rescue by hypothermia or structure-stabilizing drugs, and may retain low-level transcriptional activity at 37 °C. TP53 mutations are observed in 47% of all esophageal cancers (ECs) and 25% to 40% of gastric cancers (GCs).
View Article and Find Full Text PDFJ Funct Biomater
October 2024
We hypothesized that the different post-implantation healing stages between the conventional and immediate implantations produce different amounts and tissue composition of the peri-implant bone. Thus, the objective of the current study was to examine whether the stability of dental implant systems is associated with characteristics of the interfacial bone area at different post-implanation healing periods. Mandibular molars were extracted from each beagle dog.
View Article and Find Full Text PDFBackground: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP, with limited studies comparing combined prophylactic measures and their efficacy relative to individual patient risk profiles. This study aims to perform an individual patient data meta-analysis (IPDMA) to evaluate the contribution of patient and ERCP-related risk factors to PEP development and to identify the best prophylaxis strategies according to the patient's risk profile.
Methods: We systematically searched MEDLINE, Embase, and Cochrane databases until November 2022 for randomized controlled PEP prophylaxis trials.
An important subset of meningiomas behaves aggressively and is characterized by multiple recurrences. We identify clinical, genetic, and epigenetic predictors of multiply recurrent meningiomas (MRMs) and evaluate the evolution of these meningiomas in patient-matched samples. On multivariable binomial logistic regression, MRMs were significantly associated with male sex ( = 0.
View Article and Find Full Text PDFBackground: Risk factors for pancreatic ductal adenocarcinoma (PDAC) include tobacco/alcohol abuse, genetic predisposition, insulin resistance, and pancreatic cysts. Despite these well-established risk factors and the screening of high-risk individuals, some people still develop PDAC. This study aims to explore a potential risk factor for PDAC by investigating the association between fungal toxins (FT) and environmental toxins (ET) and the disease.
View Article and Find Full Text PDFThe genetic basis of resistance to quinine (QN), a drug used to treat severe malaria, has long been enigmatic. To gain further insight, we used FRG-NOD human liver-chimeric mice to conduct a genetic cross between QN-sensitive and QN-resistant parasites, which also differ in their susceptibility to chloroquine (CQ). By applying different selective conditions to progeny pools prior to cloning, we recovered 120 unique recombinant progeny.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis (ALS) characterized by progressive degeneration of motor neurons is a debilitating disease, posing substantial challenges in both prognosis and daily life assistance. However, with the advancement of machine learning (ML) which is renowned for tackling many real-world settings, it can offer unprecedented opportunities in prognostic studies and facilitate individuals with ALS in motor-imagery tasks. ML models, such as random forests (RF), have emerged as the most common and effective algorithms for predicting disease progression and survival time in ALS.
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