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Inflammasomes are multiprotein platforms that control caspase-1 activation, which process the inactive precursor forms of the inflammatory cytokines IL-1β and IL-18, leading to an inflammatory type of programmed cell death called pyroptosis. Studying inflammasome-driven processes, such as pyroptosis-induced cell swelling, under controlled conditions remains challenging because the signals that activate pyroptosis also stimulate other signaling pathways. We designed an optogenetic approach using a photo-oligomerizable inflammasome core adapter protein, apoptosis-associated speck-like containing a caspase recruitment domain (ASC), to temporally and quantitatively manipulate inflammasome activation...

The immune system can control cancer progression. However, even though some innate immune sensors of cellular stress are expressed intrinsically in epithelial cells, their potential role in cancer aggressiveness and subsequent overall survival in humans is mainly unknown. Here, we show that NLR family CARD Domain Containing 4 (NLRC4) is downregulated in epithelial tumor cells of colorectal cancer (CRC) patients by using spatial tissue imaging. Strikingly, only the loss of tumor NLRC4 but not stromal is associated with poor immune infiltration (mainly dendritic and CD4+/CD8+ T cells) and accurately predicts progression to metastatic Stage IV and decrease of overall survival...

When individuals make uncertain decisions, they often evaluate the correctness of their choices in what is referred to as decision-making confidence. The outcomes of such decision-making can lead to counterfactual thinking wherein alternative possible outcomes are contemplated. This, in turn, can elicit counterfactual emotions including upward and downward counterfactual thinking, which, respectively, refer to regret and relief. Decision-making confidence and counterfactual emotions have key effects on how individuals learn from the past and prepare for the future...

In response to nutrient deprivation, bacteria activate a conserved stress response pathway called the stringent response (SR). During SR activation in Caulobacter crescentus , SpoT synthesizes the secondary messengers guanosine 5'-diphosphate 3'-diphosphate and guanosine 5'-triphosphate 3'-diphosphate (collectively known as (p)ppGpp), which affect transcription by binding RNA polymerase (RNAP) to down-regulate anabolic genes. (p)ppGpp also impacts the expression of anabolic genes by controlling the levels and activities of their transcriptional regulators...

BACKGROUND: Staphylococcus aureus is a notorious multidrug resistant pathogen prevalent in healthcare facilities worldwide. Unveiling the mechanisms underlying biofilm formation, quorum sensing and antibiotic resistance can help in developing more effective therapy for S. aureus infection. There is a scarcity of literature addressing the genetic profiles and correlations of biofilm-associated genes, quorum sensing, and antibiotic resistance among S. aureus isolates from Malaysia. METHODS: Biofilm and slime production of 68 methicillin-susceptible S...

BACKGROUND: This study aimed to assess the acceptability and attitudes of women towards human papillomavirus (HPV) self-sampling and compare the effectiveness of two delivery modes utilising face-to-face and online website for cervical cancer screening in Hong Kong. METHODS: Women aged 30-65 years were invited to participate by distributing the study information pamphlets at the specialist clinics of a regional acute hospital. Those who were interested in participating were given the option to join directly face-to-face or through an online website...

Precise medical billing is essential for decreasing hospital liability, upholding environmental stewardship and ensuring fair costs for patients. We instituted a multifaceted approach to improve the billing accuracy of our robotic-assisted thoracic surgery programme by including an educational component, updating procedure cards and removing the auto-populating function of our electronic medical record. Overall, we saw significant improvements in both the number of inaccurate billing cases and, specifically, the number of cases that overcharged patients...

Obstetric violence is an urgent global problem. Recently, several studies have appeared on obstetric violence in the Netherlands, indicating that it is a more widespread phenomenon in Dutch maternity care than commonly thought. At the same time, there has been very little public outrage over these studies. The objective of this qualitative research is to gain insight into the working and normalization of obstetric violence by focusing on the moral and epistemic injustices that both facilitate obstetric violence and make it look acceptable...

AIMS: Many transgender and gender diverse (TGD) individuals have expressed concerns about the potential for oral pre-exposure prophylaxis to affect hormonal concentrations achieved from taking gender-affirming hormone therapy (GAHT). The purpose of this study was to understand the bidirectional effects between hormone and intraerythrocytic tenofovir diphosphate concentrations when switching from tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) to tenofovir alafenamide/emtricitabine (TAF/FTC) in TGD users/nonusers of GAHT...

Alongside an explosion in research and development related to large language models, there has been a concomitant rise in the creation of pretraining datasets-massive collections of text, typically scraped from the web. Drawing on the field of archival studies, we analyze pretraining datasets as informal archives-heterogeneous collections of diverse material that mediate access to knowledge. We use this framework to identify impacts of pretraining data creation and use beyond directly shaping model behavior and reveal how choices about what is included in pretraining data necessarily involve subjective decisions about values...

Brain-computer interfaces can enable rapid, intuitive communication for people with paralysis by transforming the cortical activity associated with attempted speech into text on a computer screen. Despite recent advances, communication with brain-computer interfaces has been restricted by extensive training data requirements and inaccurate word output. A man in his 40's with ALS with tetraparesis and severe dysarthria (ALSFRS-R = 23) was enrolled into the BrainGate2 clinical trial. He underwent surgical implantation of four microelectrode arrays into his left precentral gyrus, which recorded neural activity from 256 intracortical electrodes...

Risk taking behavior is a symptom of multiple neuropsychiatric disorders and often lacks effective treatments. Reward circuitry regions including the amygdala, orbitofrontal cortex, insula, and anterior cingulate have been implicated in risk-taking by neuroimaging studies. Electrophysiological activity associated with risk taking in these regions is not well understood in humans. Further characterizing the neural signalling that underlies risk-taking may provide therapeutic insight into disorders associated with risk-taking...

No abstract text is available yet for this article.

PURPOSE: The U.S. Food & Drug Administration has identified physical functioning (PF) as a core patient-reported outcome (PRO) in cancer clinical trials. The purpose of this study was to identify PF PRO measures (PROMs) in adult cancer populations and classify the PROMs by content covered (facets of PF) in each measure. METHODS: As part of the Patient Reports of Physical Functioning Study (PROPS) research program, we conducted a targeted literature review to identify PROMs that could be used in clinical trials to evaluate PF from the patient perspective...

To date, information on associations between motor skills and executive functions (EF) in autistic children is limited. The purpose of this study was to compare motor skills and EF performance between autistic children and typically developing (TD) children and to examine the relationships between motor skills and EF in these two groups. Forty-eight autistic children and 48 TD children aged 6 to 12 years were recruited for this study. Motor skills were measured with the Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2)...

INTRODUCTION: Persistent somatic symptoms and functional disorders (PSS/FD) are often complex conditions requiring care from multiple disciplines. One way of bringing the different disciplines together is through collaborative care. Little is known about the implementation barriers faced and relevant strategies to tackle the barriers in this field. Therefore, using expert knowledge, we aim to develop realistic strategies for dealing with implementation barriers of collaborative care in PSS/FD...

BACKGROUND: Substantial variation exists in surgeon decision making. In response, multiple specialty societies have established criteria for the appropriate use of spine surgery. Yet few strategies exist to facilitate routine use of appropriateness criteria by surgeons. Behavioral science nudges are increasingly used to enhance decision making by clinicians. We sought to design "surgical appropriateness nudges" to support routine use of appropriateness criteria for degenerative lumbar scoliosis and spondylolisthesis...

IMPORTANCE: Stroke survivors experience changes in participation level, satisfaction with participation, and participation balance, making it necessary to have a validated tool for their assessment. OBJECTIVE: To evaluate the psychometric properties of the Spanish version of the Satisfaction With Daily Occupations and Occupational Balance (SDO-OB) in stroke survivors. DESIGN: Psychometric study. SETTING: National multicenter study (rehabilitation centers, and hospitals)...

BACKGROUND: Therapeutic drug monitoring (TDM) of antipsychotics for dose titration or detection of noncompliance is not uncommon in daily practice. Normally, TDM implies measuring a drug concentration in venous blood samples. This technique is invasive and requires trained assistants and patients normally need to go to an outpatient clinic. Over the past decades, sensitivity of analytical equipment has improved leading to a growing interest in microsampling techniques. These techniques are minimally invasive, require a small volume (<100 μL), usually result in stable samples, and can be collected by the patient or a caregiver at home...

We delve into the temporal dynamics of public transportation (PT) ridership in Seoul, South Korea, navigating the periods before, during, and after the COVID-19 pandemic through a spatial difference-in-difference model (SDID). Rooted in urban resilience theory, the study employs micro-level public transportation card data spanning January 2019 to December 2023. Major findings indicate a substantial ridership decline during the severe COVID impact phase, followed by a period in the stable and post-COVID phases...