Browse Articles

Perceived social support, marital satisfaction, and resilience in women with abortion experience through structural equation modeling

Development and application of microcapsules based on rice husk and metallurgical sludge to improve soil fertility

Pt/IrOx enables selective electrochemical C-H chlorination at high current

Single-cell data reveal heterogeneity of investment in ribosomes across a bacterial population

Dropping the baton: Cognitive biases in emergency physicians

Introduction Clinical medicine is becoming more complex and increasingly requires a team-based approach to deliver healthcare needs. This dispersion of cognitive reasoning across individuals, teams and systems (termed “distributed cognition”) means that our understanding of cognitive biases and errors must expand beyond traditional “in-the-head” individual mental models and focus on a broader “out-in-the-world” context instead. To our knowledge, no qualitative studies thus far have examined cognitive biases in clinical settings from a team-based sociocultural perspective. Our study therefore seeks to explore how cognitive biases and errors among emergency physicians (EPs) arise due to sociocultural influences and lapses in team cognition. Methodology Our study team comprised four EPs of different seniorities from three different institutions and local and international academics who provided qualitative methodological guidance. We adopted a constructivist paradigm and employed a reflexive thematic analysis approach which acknowledged our researcher reflexivity. We conducted seven focus group discussions with 25 EPs who were purposively sampled for maximum variation. Our research question was: How do sociocultural factors lead to cognitive biases and medical errors among EPs? Results Our themes coalesce around sociocultural pressures related to team psychology. In theme one, the EP is compelled by sociocultural pressures to blindly trust colleagues. In the second, the EP is obliged by cultural norms to be “nice” and neatly summarise cases into illness scripts during handovers. In the last, the EP is under immense pressure to follow conventional wisdom, comply with clinical protocols and not challenge inpatient specialists. Conclusion Cognitive biases and errors in clinical decision-making can arise due to lapses in distributed team cognition. Although this study focuses on emergency medicine, these pitfalls in team-based cognition are relevant across the entire continuum of care and across all specialties of medicine. The hyperacute nature of emergency medicine merely exacerbates and condenses these into a compressed timeframe. Indeed, similar relays are run every day in every discipline of medicine, with the same unified goal of doing the best for our patients while not committing cognitive errors and dropping the baton.

Estimating the prevalence of six common respiratory viral infections in Zhangzhou, China using nasopharyngeal swabs in adults and throat swabs in Children

SLC35A2 is a novel prognostic biomarker and promotes cell proliferation and metastasis via Wnt/β-catenin/EMT signaling pathway in breast cancer

Generalized cue reactivity in rat dopamine neurons after opioids

AbstractCue reactivity is the maladaptive neurobiological and behavioral response upon exposure to drug cues and is a major driver of relapse. A widely accepted assumption is that drugs of abuse result in disparate dopamine responses to cues that predict drug vs. natural rewards. The leading hypothesis is that drug-induced dopamine release represents a persistently positive reward prediction error that causes runaway enhancement of dopamine responses to drug cues, leading to their pathological overvaluation. However, this hypothesis has not been directly tested. Here, we develop Pavlovian and operant procedures in male rats to measure firing responses within the same dopamine neurons to drug versus natural reward cues, which we find to be similarly enhanced compared to cues predicting natural rewards in drug-naive controls. This enhancement is associated with increased behavioral reactivity to the drug cue, suggesting that dopamine neuronal activity may still be relevant to cue reactivity, albeit not as previously hypothesized. These results challenge the prevailing hypothesis of cue reactivity, warranting revised models of dopaminergic function in opioid addiction, and provide insights into the neurobiology of cue reactivity with potential implications for relapse prevention.

The global RNA-binding protein RbpB is a regulator of polysaccharide utilization in Bacteroides thetaiotaomicron

AbstractParamount to human health, symbiotic bacteria in the gastrointestinal tract rely on the breakdown of complex polysaccharides to thrive in this sugar-deprived environment. Gut Bacteroides are metabolic generalists and deploy dozens of polysaccharide utilization loci (PULs) to forage diverse dietary and host-derived glycans. The expression of the multi-protein PUL complexes is tightly regulated at the transcriptional level. However, how PULs are orchestrated at translational level in response to the fluctuating levels of their cognate substrates is unknown. Here, we identify the RNA-binding protein RbpB and a family of noncoding RNAs as key players in post-transcriptional PUL regulation. We demonstrate that RbpB interacts with numerous cellular transcripts, including a paralogous noncoding RNA family comprised of 14 members, the FopS (family of paralogous sRNAs). Through a series of in-vitro and in-vivo assays, we reveal that FopS sRNAs repress the translation of SusC-like glycan transporters when substrates are limited—an effect antagonized by RbpB. Ablation of RbpB in Bacteroides thetaiotaomicron compromises colonization in the mouse gut in a diet-dependent manner. Together, this study adds to our understanding of RNA-coordinated metabolic control as an important factor contributing to the in-vivo fitness of predominant microbiota species in dynamic nutrient landscapes.

Incident duration prediction through integration of uncertainty and risk factor evaluation: A San Francisco incidents case study

Predicting incident duration and understanding incident types are essential in traffic management for resource optimization and disruption minimization. Precise predictions enable the efficient deployment of response teams and strategic traffic rerouting, leading to reduced congestion and enhanced safety. Furthermore, an in-depth understanding of incident types helps in implementing preventive measures and formulating strategies to alleviate their influence on road networks. In this paper, we present a comprehensive framework for accurately predicting incident duration, with a particular emphasis on the critical role of street conditions and locations as major incident triggers. To demonstrate the effectiveness of our framework, we performed an in-depth case study using a dataset from San Francisco. We introduce a novel feature called "Risk" derived from the Risk Priority Number (RPN) concept, highlighting the significance of the incident location in both incident occurrence and prediction. Additionally, we propose a refined incident categorization through fuzzy clustering methods, delineating a unique policy for identifying boundary clusters that necessitate further modeling and testing under varying scenarios. Each cluster undergoes a Multiple Criteria Decision-Making (MCDM) process to gain deeper insights into their distinctions and provide valuable managerial insights. Finally, we employ both traditional Machine Learning (ML) and Deep Learning (DL) models to perform classification and regression tasks. Specifically, incidents residing in boundary clusters are predicted utilizing the scenarios outlined in this study. Through a rigorous analysis of feature importance using top-performing predictive models, we identify the "Risk" factor as a critical determinant of incident duration. Moreover, variables such as distance, humidity, and hour demonstrate significant influence, further enhancing the predictive power of the proposed model.

The Hira complex regulates Gli3R-dependent transcription in Hedgehog signaling and medulloblastoma cell growth and migration

TILTomorrow today: dynamic factors predicting changes in intracranial pressure treatment intensity after traumatic brain injury

AbstractPractices for controlling intracranial pressure (ICP) in traumatic brain injury (TBI) patients admitted to the intensive care unit (ICU) vary considerably between centres. To help understand the rational basis for such variance in care, this study aims to identify the patient-level predictors of changes in ICP management. We extracted all heterogeneous data (2008 pre-ICU and ICU variables) collected from a prospective cohort (n = 844, 51 ICUs) of ICP-monitored TBI patients in the Collaborative European NeuroTrauma Effectiveness Research in TBI study. We developed the TILTomorrow modelling strategy, which leverages recurrent neural networks to map a token-embedded time series representation of all variables (including missing values) to an ordinal, dynamic prediction of the following day’s five-category therapy intensity level (TIL(Basic)) score. With 20 repeats of fivefold cross-validation, we trained TILTomorrow on different variable sets and applied the TimeSHAP (temporal extension of SHapley Additive exPlanations) algorithm to estimate variable contributions towards predictions of next-day changes in TIL(Basic). Based on Somers’ Dxy, the full range of variables explained 68% (95% CI 65–72%) of the ordinal variation in next-day changes in TIL(Basic) on day one and up to 51% (95% CI 45–56%) thereafter, when changes in TIL(Basic) became less frequent. Up to 81% (95% CI 78–85%) of this explanation could be derived from non-treatment variables (i.e., markers of pathophysiology and injury severity), but the prior trajectory of ICU management significantly improved prediction of future de-escalations in ICP-targeted treatment. Whilst there was no significant difference in the predictive discriminability (i.e., area under receiver operating characteristic curve) between next-day escalations (0.80 [95% CI 0.77–0.84]) and de-escalations (0.79 [95% CI 0.76–0.82]) in TIL(Basic) after day two, we found specific predictor effects to be more robust with de-escalations. The most important predictors of day-to-day changes in ICP management included preceding treatments, age, space-occupying lesions, ICP, metabolic derangements, and neurological function. Serial protein biomarkers were also important and may serve a useful role in the clinical armamentarium for assessing therapeutic needs. Approximately half of the ordinal variation in day-to-day changes in TIL(Basic) after day two remained unexplained, underscoring the significant contribution of unmeasured factors or clinicians’ personal preferences in ICP treatment. At the same time, specific dynamic markers of pathophysiology associated strongly with changes in treatment intensity and, upon mechanistic investigation, may improve the timing and personalised targeting of future care.

Hypoxia-tolerant polymeric photosensitizer prodrug for cancer photo-immunotherapy

Intratumor heterogeneity of EGFR expression mediates targeted therapy resistance and formation of drug tolerant microenvironment

AbstractEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used to treat non-small cell lung cancers with EGFR mutations, but drug resistance often emerges. Intratumor heterogeneity is a known cause of targeted therapy resistance and is considered a major factor in treatment failure. This study identifies clones of EGFR-mutant non-small cell lung tumors expressing low levels of both wild-type and mutant EGFR protein. These EGFR-low cells are intrinsically more tolerant to EGFR inhibitors, more invasive, and exhibit an epithelial-to-mesenchymal-like phenotype compared to their EGFR-high counterparts. The EGFR-low cells secrete Transforming growth factor beta (TGFβ) family cytokines, leading to increased recruitment of cancer-associated fibroblasts and immune suppression, thus contributing to the drug-tolerant tumor microenvironment. Notably, pharmacological induction of EGFR using epigenetic inhibitors sensitizes the resistant cells to EGFR inhibition. These findings suggest that intrinsic drug resistance can be prevented or reversed using combination therapies.

Self /other recognition and distinction in adolescents with anorexia nervosa: A pilot study using a double mirror paradigm

Background Abnormalities in body perception in patients affected by anorexia nervosa have been widely studied, but without explicit reference to their relationship to others and the social processes involved. Yet, there are a several arguments supporting impairments in interpersonal relationships in these patients. Notably, some evidence suggests that self/other distinction (SOD), the ability to distinguish one’s own body, actions and mental representations from those of others could be impaired. But research remains scarce in this area. Material and methods A single-centre, prospective pilot study was conducted to investigate, for the first time, self-recognition and SOD in seven adolescents with anorexia nervosa compared with matched healthy controls (HCs) using the "Alter Ego"TM double mirror paradigm. This innovative device allows the progressive morphing of one’s own face to that of another and vice versa between two subjects that interact on opposite sides of the device. Two judgement criteria were used: 1) M1: the threshold at which subjects start to recognize their own face during other-to-self morphing, and 2) M2: the threshold at which subjects start to recognize the other’s face during self-to-other morphing. In a second part, SOD was reassessed during five different sensorimotor tasks aimed at increasing body self-consciousness in participants with anorexia nervosa. Results The results showed that the participants with anorexia nervosa exhibited earlier self-recognition in the other-to-self sequence and delayed other-recognition in the self-to-other sequence. Furthermore, in contrast with that of HCs, the critical threshold for switching between self and other varied with the direction of morphing in anorexia nervosa participants. Finally, when participants with anorexia were seated in a chair with a backrest and footrest strengthening the median axis of their body, the self-recognition threshold (M1) increased significantly, approaching that of controls. Conclusions Although additional research is needed to replicate the results of this pilot study, it revealed the first behavioural evidence of altered SOD in individuals affected by anorexia nervosa through an embodied, semiecological face-recognition paradigm. The relationships between anomalies in body perception and alterations in interpersonal relationships are discussed within an integrative framework from phenomenology to neuroscience, and new research and therapeutic perspectives are presented.

In vitro assays identified thiohydantoins with anti-trypanosomatid activity and molecular modelling studies indicated possible selective CYP51 inhibition

Assessment of the efficacy of on-demand tegoprazan therapy in gastroesophageal reflux disease through a randomized controlled trial

Deciphering the effect of UM171 on human hematopoietic progenitor cell fate through clonal analysis

Dynamics of specialization in neural modules under resource constraints

AbstractThe brain is structurally and functionally modular, although recent evidence has raised questions about the extent of both types of modularity. Using a simple, toy artificial neural network setup that allows for precise control, we find that structural modularity does not in general guarantee functional specialization (across multiple measures of specialization). Further, in this setup (1) specialization only emerges when features of the environment are meaningfully separable, (2) specialization preferentially emerges when the network is strongly resource-constrained, and (3) these findings are qualitatively similar across several different variations of network architectures. Finally, we show that functional specialization varies dynamically across time, and these dynamics depend on both the timing and bandwidth of information flow in the network. We conclude that a static notion of specialization is likely too simple a framework for understanding intelligence in situations of real-world complexity, from biology to brain-inspired neuromorphic systems.

Comparison of core temperature using tracheal thermometer and pulmonary artery catheter in adult patients undergoing coronary artery bypass graft surgery

Background Monitoring core temperature is important for patients under anesthesia. Esophageal and pulmonary artery blood temperatures can be used for measuring core temperature during general anesthesia. However, these methods pose challenges, especially when the placement of an esophageal thermometer and pulmonary artery catheter (PAC) is either impractical or not the preferred approach. An endotracheal tube (ETT) with a thermometer on the cuff allows for the measurement of tracheal temperature, providing a suitable alternative to core temperature measurement. This study aimed to assess the clinical reliability and accuracy of the thermometer in the ETT in comparison to the core temperature measured using a PAC. Methods Eleven patients who underwent coronary artery bypass graft (CABG) surgery were enrolled in this study. The patients were intubated using an ETT equipped with a thermometer on the cuff, and a PAC was inserted. Temperature measurements of both the trachea and pulmonary artery blood were recorded at 5-minute intervals for 1 hour before starting cardiopulmonary bypass. The agreement between the two temperature measurement methods was investigated using the Bland-Altman plot with multiple measurements per subject, and the correlation was evaluated using the concordance correlation coefficient (CCC). Results Eleven patients with a total of 143 pairs of data were included for analysis. The mean difference between the tracheal and pulmonary artery temperatures was −0.10°C. The 95% limit of agreement (LoA), calculated as ± 1.96 standard deviation, ranged from −0.35°C to 0.15°C. The 95% confidence interval for the lower and upper LoA was −0.51°C to −0.27°C and 0.07°C to 0.31°C, respectively. The maximum allowed difference (Δ) was set at 0.5°C. The majority of temperature differences fell within the LoA and were well below the maximum allowed difference. The CCC was 0.95, which indicates a substantial strength of agreement. Conclusions The agreement between the tracheal and pulmonary artery temperature measurements using the ETT thermometer and pulmonary artery catheter, respectively, was found to be clinically reliable and accurate. Therefore, the tracheal temperature measurement can effectively represent the core temperature of the patients. Employing an ETT equipped with a thermometer on the cuff can serve as a reliable and independent method for measuring core temperature. Trial registration Clinical trial registration number: NCT05595616.