There has been a lot of interest in the field of laboratory medicine regarding the use of machine learning (ML)-based prediction models. The longitudinal ML-based Serum Tumor marker-based Outcome Prediction (STOP) model was previously developed to identify non-small cell lung cancer (NSCLC) patients who do not respond to immune checkpoint inhibitor treatment. Due to significant preanalytical challenges with the NSE tumor marker, the best-performing alternative model, mSTOP model based on CEA and Cyfra 21-1, was selected for validation of its diagnostic accuracy, clinical- and financial impact. Diagnostic accuracy was based on a dual-center validation cohort of 242 metastatic NSCLC patients. The clinical and financial impact of mSTOP was investigated using a previously described Discrete Event Simulation (DES) model with under-treatment, overtreatment, and financial impact as output parameters. Finally, an ICT system and a multi-parametric QC strategy were designed to enable real-time operation and quality control of mSTOP. mSTOP identified 35.1 % of nonresponding patients, with a positive predictive value (PPV) of 84.8 %, which was comparable to CT-imaging. In combination with CT- imaging, the PPV increased to 95.7 %, identifying 19.8 % of non-responding patients. Estimated avoided overtreatment ranged from 6.7 % to 17.4 %, reflecting a financial savings of €569 to €5306 per patient, depending on the clinical mSTOP scenario used. The developed ICT system incorporated the mSTOP algorithm within the laboratory and healthcare information system. It allowed for continuous real-time mSTOP calculations. The obtained diagnostic mSTOP characteristics and their corresponding clinical and financial characteristics prompted the development of an ICT system that supports automated, real-time, clinical application.
To evaluate the impact of continuing versus stopping biologic disease-modifying anti-rheumatic drugs (bDMARDs) during the perioperative period on surgical site infections (SSIs), delayed wound healing, and disease flares in patients with inflammatory arthritis (IA) undergoing elective non-orthopaedic surgery. We conducted a systematic review of observational studies assessing the perioperative management of bDMARDs in IA patients undergoing elective non-orthopaedic surgery. Searches were conducted across seven databases and trial registries from the year 2000 onwards. Eligible studies compared outcomes in patients who continued versus stopped biologic therapy. Risk of bias was assessed using the ROBINS-I tool and due to heterogeneity data were synthesised narratively. Eight observational studies met the inclusion criteria. All studies were at moderate or serious risk of bias. Four studies compared infections with two suggesting higher infection rates in the stop biologic group. Two studies assessed delayed wound healing, both suggesting higher rates in the stop group. Disease flares were more common in patients who stopped biologics in all three of the studies reporting this outcome. No studies assessed health-related quality of life. The available observational evidence does not demonstrate a consistent increase in postoperative infection or wound complications related to biologic continuation, however, confidence in these findings is limited by serious risk of bias and outcome heterogeneity. High-quality randomised controlled trials are needed to inform the perioperative management guidelines for IA patients undergoing elective non-orthopaedic procedures.
Stigmatizing attitudes toward individuals with mental disorders represent a major barrier to treatment, recovery, and social inclusion. The present research introduces and psychometrically evaluates the German-language Stigma Toward People with Mental Disorders scale (SToP-MD) across three independent studies with distinct samples.In study 1 (N = 266), an initial item pool was developed and refined based on theoretical frameworks and exploratory factor analysis. In study 2 (N = 448), confirmatory factor analysis supported a two-factor structure comprising prejudiced stigmatization (SToP-MD-PS) and assumption of problems (SToP-MD-AP). The model demonstrated adequate fit according to conventional indices (CFI = 0.97, TLI = 0.96, SRMR = 0.07), although robust indices indicated only moderate fit (robust CFI = 0.91, robust RMSEA = 0.13). Internal consistency was good for the PS subscale (ω = 0.83) but limited for the AP subscale (ω = 0.51). In study 3 (N = 266), the scale's sensitivity to short-term change was examined following exposure to differently framed media content.As hypothesized, the SToP-MD subscales were positively associated with depression stigma (DSS) and social distance (SDI), and negatively correlated with openness and agreeableness (NEO-FFI), supporting convergent validity. Discriminant validity was partially confirmed by low or non-significant correlations with attitudes toward physically disabled individuals (ATDP), suicide-related cognitions (CCSS), and socially desirable responding (BIDR).Across all three studies, the SToP-MD demonstrated preliminary yet consistent evidence of structural and construct validity, as well as change sensitivity. It captures both overt prejudices and implicit burden assumptions, offering a nuanced assessment of public stigma toward mental disorders. The scale can serve as a valuable tool in stigma research, public health monitoring, and evaluation of interventions. Future research should extend validation to more diverse samples and test predictive and longitudinal utility.
The integration of the multitude of ultrasound techniques into a "one-stop" liver clinic model will revolutionize the management of liver diseases. This approach streamlines patient care by providing immediate imaging assessment, facilitating prompt diagnosis, and expediting treatment plans. The traditional ultrasound methods of B-mode imaging and Doppler techniques have been supplemented by the newer techniques of tissue elastography, fat quantification, and contrast-enhanced ultrasound-termed multiparametric ultrasound. The deployment of these techniques to establish in more detail the underlying status of liver disease has been profound. The encompassing ultrasound techniques have allowed the ultrasound practitioner to establish a comprehensive assessment of liver disease, allowing further accurate management, and negating the need for additional, often more expensive, imaging to establish the diagnosis. This paper explores the implementation, benefits, and challenges of ultrasound-based one-stop liver clinics, emphasizing their impact on patient outcomes and healthcare efficiency. A detailed assessment of the techniques and their position in the diagnostic armamentarium is reviewed with a comprehensive overview established. CRITICAL RELEVANCE STATEMENT: Multiparametric liver ultrasound integrating B-mode, Doppler, CEUS, elastography and fat quantification provides a practical, low-cost one-stop pathway for staging chronic liver disease, assessing portal hypertension surrogates and characterizing incidental lesions, thereby speeding up treatment. KEY POINTS: Ultrasound is the first-line imaging investigation for liver disease, with established criteria on B-mode imaging for steatosis and cirrhosis. Multiparametric ultrasound integrates morphology, hemodynamics, fibrosis, steatosis, and lesion assessment. A one-stop liver ultrasound clinic accelerates decisions and reduces additional imaging.
Dance integrates physical movement with cognitive and emotional processes, offering unique benefits beyond mere exercise. While previous studies have explored the impact of dance on response inhibition, the mechanisms by which irrelevant emotional stimuli modulate inhibition in dancers remains unclear. This study investigated the role of dance in modulating response inhibition in emotional and non-emotional contexts. We compared dancers and non-dancers on two response inhibition tasks: the non-emotional stop-signal task (NESST) and the emotional stop-signal task (ESST), which examined inhibition in the presence of irrelevant emotional information. Participants also completed self-report measures of mood, affect, and behavioural inhibition and activation systems. There was no group differences emerged for inhibition on the NESST. However, in the ESST, significant main effects of group and emotion were observed along with the significant interaction effect. Dancers showed a better response inhibition than non-dancers when faced with stop signals with irrelevant happy facial expression. Within the dancer group, happy faces uniquely enhanced response inhibition compared to angry and neutral faces, indicating a distinct modulation of cognitive processing by positive emotional stimuli in dancers. Dancers also reported lower depression and stress, higher positive affect, and more balanced behavioural activation profiles. The results are interpreted through functional perspectives on how dance, by fostering eudaimonic well-being and pleasurable engagement, may enhance the efficient allocation of attention to emotional stimuli. Overall, the findings suggest that dance training is associated with better response inhibition in perceptually emotionally salient contexts, particularly when processing positive emotional faces, highlighting its potential for cognitive-emotional enhancement.
To identify risk factors for distal adding-on (AO) in Lenke 1 C/2 C AIS patients with the lowest instrumented vertebra (LIV) at the lumbar apex vertebra (LAV). This study included 60 Lenke 1 C/2 C AIS patients undergoing posterior spinal fusion with LIV at LAV and > 2 years follow-up. Patients were categorized into AO (n = 17) and non-AO (n = 43) groups. Radiographic analysis assessed thoracic/lumbar curve flexibility, apical vertebral translation (AVT), LAV rotation/tilt, coronal balance, Harrington stable zone on anteroposterior(AP)and concave-side bending films, and LAV/AV + 1 disc opening/closing status. Clinical outcomes used SRS-22. Statistical comparison was performed. The AO group exhibited significantly poorer preoperative thoracic curve flexibility, greater coronal imbalance toward the lumbar convex side, larger lumbar AVT, smaller Harrington stable zones, and fewer patients with favorable LAV/AV + 1 disc status. Logistic regression identified thoracic flexibility, Harrington stable zone on concave-side bending, and disc status as significant AO predictors. Optimal thresholds for selecting LAV as LIV were thoracic flexibility > 47.4% ,concave-side bending Harrington zone > 84.9% ,and favorable opening/closing status of the LAV/AV + 1 disc .At final follow-up, the AO group had larger lumbar Cobb angle and AVT with lower correction rates, but SRS-22 scores showed no significant difference. For Lenke 1 C/2 C AIS, terminating LIV at LAV is feasible when thoracic flexibility is good (> 47.4%), the LAV/AV + 1 disc status is favorable, and the Harrington stable zone on concave-side bending is large (> 84.9%).
Psychopathy involves disruptions in affiliation and threat sensitivity, but these are hard to disentangle behaviorally. This preregistered study (independent sample Ns = 175 and 173) used clinical-forensic and transdiagnostic measures relevant to psychopathy and an adapted interpersonal distance task. Participants indicated preferred proximity to different targets ranging in affiliation and threat after describing each target in their own words. As expected, participants preferred closer proximity to affiliative targets (e.g., a friend) versus threatening ones (e.g., a thief). However, psychopathic traits did not predict interpersonal proximity preferences. Notably, psychopathic traits (Factor 2; antagonism) were linked to response inconsistency, suggesting task disengagement. Exploratory findings showed that participants high in antagonism used more negative language to describe strangers, suggesting hostile attribution bias; however, this was unrelated to task behavior. Overall, the task did not reveal clear socioemotional differences linked to psychopathy. More engaging, ecologically valid methods are needed to better assess affiliation and threat processing in psychopathy.
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Immunotherapy has transformed the treatment landscape of advanced and metastatic non-small cell lung cancer, providing durable survival benefits for a subset of patients. Despite widespread adoption of immune checkpoint inhibitors as frontline therapy, the optimal duration of treatment remains uncertain. Current practice often limits therapy to 2 years or continues indefinitely until progression based on landmark clinical trials that arbitrarily chose these timepoints, and it is not biologically based. Unfortunately, there is still limited prospective or clinical trial evidence to guide such decisions. Retrospective studies have suggested that discontinuation at 2 years may not compromise outcomes, but also raise concerns about balancing efficacy with cumulative toxicities and financial burden. This review provides updated data and ongoing trials seeking to answer these questions, along with potential emerging biomarkers, including circulating tumor DNA (ctDNA) and imaging with positron emission tomography/computed tomography that can help risk-stratify and guide and refine treatment strategies.
Single-fraction stereotactic ablative radiotherapy (SABR) is a curative treatment option for patients with early lung cancer. We undertook a feasibility study to assess whether simulation, planning and treatment could be undertaken within a single day and whether this expedited pathway was acceptable to patients. A multidisciplinary team of radiation oncologists, radiation therapists and medical physicists developed a workflow to permit all aspects of planning and treatment to be conducted within a single working day. All aspects of the pathway were timed. Prescription dose was 30 Gray. Patients completed an Experience Survey within two weeks of treatment. The study would be deemed successful if it met both dual primary endpoints of feasibility (7/10 patients treated within 8 working hours) and patient satisfaction (7/10 expressing overall satisfaction). Ten patients were treated. These included 6 women and 4 men. Median age was 76.5 and 9 patients had been deemed to be medically inoperable. Median time from commencement of CT simulation to end of treatment was 6 h 50 min (IQR 6 h 42 m - 7 h 4 m); 9/10 patients were treated within the target 8-hour window. All 10 patients expressed overall satisfaction with the service. All 10 felt it was more convenient than our usual treatment pathway would have been. Same-day single-fraction SABR is feasible and acceptable to patients. This pathway should be considered for those who live a significant distance from treatment centres or who have other difficulties in attending for multiple visits.
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This dataset provides real-world last-mile delivery routes from a logistics company, offering valuable resources for research in route optimization and logistics. The dataset addresses a substantial gap between theoretical route planning and routing performed by drivers who often do not follow the proposed routes. The dataset comprises 19,497 pairs of routes, including both planned routes, generated by human dispatchers employing heuristic optimization tools, and the routes that the drivers eventually followed in practice. The routes were completed by 400 unique drivers, covering 10,864 unique locations. In the dataset, the routes are presented as sequences of stops, where each stop is a separate row in the presented datafile. The dataset includes detailed information on routes, stops and drivers' identifiers, timing, and distance measurements. It allows for a deeper analysis of driver behavior patterns, factors of route deviations, and their impact on delivery performance.
Preparing samples for analysis by mass spectrometry (MS) can be laborious and challenging. Hyphenated separation tools are convenient but costly and require much attention. Here, we present a facile low-cost online MS method for analysis of complex samples. It relies on a standard unmodified electrospray ionization (ESI) source, which incorporates polyether ether ketone tubing connected to a grounded metal union or diverter valve. The sample is infused by a syringe pump, and the flow is stopped. During the stopped-flow stage, ionic species are spontaneously separated due to the electric field between the ESI capillary and the grounded element. The flow is then restarted, and the separated species pass to the ion source. The signals of analytes are enhanced with respect to the signals obtained during direct infusion. This enhancement is attributed to the microseparation of analyte and matrix ions occurring in the sample flow line section. The signal change factors ranged from 0.74 to 295. The reported intrinsic property of ESI─operated in a run-stop-run sequence─has broad applicability in analysis of metabolites, peptides, and proteins in complex matrices. Given the tens of thousands of ESI-MS systems used worldwide, this fundamental finding could have broad applicability.
What is this plain language review about?This review describes findings from FINEARTS-HF, a study that assessed finerenone (or KERENDIA®) for treating heart failure with mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF). In FINEARTS-HF, HFmrEF was defined as an ejection fraction between 40% and 49%, meaning the heart pumps out less blood than usual. HFpEF was defined as an ejection fraction of 50% or more, meaning the heart’s main pumping chamber (the left ventricle) is too stiff and unable to relax properly between beats, which increases pressure inside the heart, causing symptoms of heart failure.What did the researchers want to find out?Researchers investigated whether finerenone (as opposed to placebo) could reduce the chance of heart failure events or deaths from heart-related or blood circulation causes in people with HFmrEF or HFpEF who were already receiving standard heart failure treatment.What were the results?During their time in the study (about 32 months), people who took finerenone were 16% less likely to experience heart failure events or death from heart-related or blood circulation causes than those who took placebo. The results were similar in men and women, people of different ages, people with different medical conditions, and people taking other medications for heart failure.Side effects were mostly similar except that more people taking finerenone (1 in 7) had potassium levels that were too high versus those who took placebo (1 in 14), and more people taking placebo (1 in 10) had potassium levels that were too low versus those who took finerenone (1 in 25). Having potassium levels that are too high or too low can lead to heart rhythm problems, and in severe cases, the heart can suddenly stop beating. There were no deaths in the study due to high or low potassium levels. Potassium-related side effects can be managed with regular monitoring of laboratory potassium levels (part of a structured follow-up plan), changes in diet, and/or changing other medications.What do the results of FINEARTS-HF mean?These results show that finerenone can help stop heart failure from worsening, reduce the risks of hospital or emergency room admissions, and reduce the risk of death in people with HFmrEF or HFpEF. These results are important because there are currently fewer treatment options for HFmrEF or HFpEF than another type of heart failure where ejection fraction is reduced to less than 40% (HFrEF).
The PE_PGRS gene family in Mycobacterium tuberculosis exhibits extensive sequence variability across genotypes, which is consistent with antigenic divergence. Here we investigate how Mtb-despite lacking horizontal gene transfer-balances genomic stability with adaptive plasticity. Comparative analysis of 88 bacterial genomes reveals that PE_PGRS genes exhibit features facilitating mutability, including a significantly elevated CGGC tetramer density (mean 4.97 per 100 nt; range 1.7-7.4) compared with the genome-wide average (1.62 per 100 nt; p = 0.011) and depleted in out-of-frame stop codons, potentially conferring robustness to 1-nt and 2-nt frameshifts. Computational predictions suggest that CGGC motifs may promote secondary DNA structures, potentially destabilizing replication and contributing to replication errors, while the scarcity of out-of-frame stop codons allows continued translation beyond frameshifts, leading to changes in protein sequence and length. This dual organization may contribute to the observed adaptability of M. tuberculosis and could highlight a broader principle by which some pathogens evolve under strong constraints on horizontal gene transfer. We propose that CGGC-rich regions may function as programmed mutational hotspots across a wide range of microorganisms.
Genetically encoded calcium indicators such as GCaMP enable us to monitor neuronal activities from living animals at synaptic levels as well as at whole-brain levels. However, the genetic variation of GCaMP transgenic rats is limited compared with the various demands for neuroscience studies on rats. We established two transgenic rat lines: one expressing Cre recombinase under the control of the Thy1 promoter and another knock-in line carrying a floxed STOP cassette followed by GCaMP8 inserted into the β-actin locus. We mated these two transgenic rats and produced the Thy1-Cre-driven GCaMP8-expressing rats. Approximately 80% of cortical neurons were positive for the GCaMP immunoreactivity. The GCaMP8-expressing rats were subjected to transcranial calcium imaging from the auditory cortex under anesthesia. With this simple procedure, we were able to detect the maximum responses to 68 dB click sounds;ΔF/F0 = 1.2%. The rise time reaching the peak response was approximately 150 ms, and the half decay time was about 150 ms. These results suggest that the present GCaMP8-expressing rats as well as their parental transgenic rat strains offer a new tool for cortical macro-imaging and functional mapping with the transcranial approach.
Birth defects are a significant contributor to neonatal and under-five deaths. The majority of birth defects, once diagnosed, need multidisciplinary referrals. A Birth Defect Clinic (BDC) was therefore initiated as a one-stop clinic where all concerned specialists are available at the same place and time. An integrated approach to managing birth defects can possibly improve patient care and outcomes. The objective of the study was to evaluate the effectiveness of a multidisciplinary BDC in managing antenatally diagnosed congenital anomalies. A retrospective study of 1549 antenatal patients counseled at the BDC was conducted. Data on epidemiology, prognosis, management options, and follow-up outcomes were analyzed. The most common anomalies diagnosed were of the genitourinary system (35.95%), followed by cardiovascular system (21.82%), central nervous system (19.75%), and gastrointestinal (7.74%) anomalies. 61.8% of patients could be contacted for postnatal follow-up, with 21.5% not undergoing any postnatal evaluation. 12.58% of patients underwent Medical Termination of Pregnancy. The BDC provides a comprehensive and integrated approach to managing birth defects, improving patient care and outcomes.
Alterations in motor inhibition (MI) may be involved in the homotypic and heterotypic developmental pathways of substance use disorders (SUDs) and related conditions (e.g., binge drinking). However, no studies have clarified the neuro-behavioral correlates of MI across the various conditions (e.g., ADHD and major depressive disorder in childhood/adolescence) constituting developmental trajectories of SUDs and related problems, especially within a self-regulation conceptual framework. A multi-method meta-analysis (i.e., voxel-based, network, and multilevel) of MI tasks (i.e., Go/No-Go; Stop Signal) was conducted. Neuroimaging (fMRI) and event-related potential (ERP) data were analyzed. The study included children and adolescents with ADHD, adolescents with major depressive disorder, and subjects with SUDs and related conditions. Sixty-eight studies (fMRI: 42; ERPs: 26) were included. The analysis showed a shared increased responsiveness of the rostral anterior cingulate cortex among conditions of interest during "No-Go" trials compared to healthy controls (HCs). Reduced N200/P300 waves, together with increased reaction times in response to MI task experimental conditions, were found among conditions of interest compared to HCs. Network meta-analysis results showed that distinct patterns of neural activity linked to different self-regulation domains differentiated these clinical conditions from one another. Common and distinct patterns of neuro-behavioral responses associated with self-regulation mechanisms, especially regarding MI, should be considered key latent dimensions involved in the homotypic and heterotypic developmental pathways of SUDs and related problems.