Topology-based Clustering of Functional Brain Networks in an Alzheimer's Disease Cohort.

Alzheimer's disease is a progressive neurodegenerative disease with many identifying biomarkers for diagnosis. However, whole-brain phenomena, particularly in functional MRI modalities, are not fully understood nor characterized. Here we employ the novel application of topological data analysis (TDA)-based methods of persistent homology to functional brain networks from ADNI-3 cohort to perform a subtyping experiment using unsupervised clustering techniques. We then investigate variations in QT-PAD challenge features across the identified clusters. Using a Wasserstein distance kernel with a variety of clustering algorithms, we found that the 0th-homology Wasserstein distance kernel and spectral clustering yielded clusters with significant differences in whole brain and medial temporal lobe (MTL) volume, thus demonstrating an intrinsic link between whole brain functional topology and brain morphometric structure. These findings demonstrate the importance of MTL in functional connectivity and the efficacy of using TDA-based machine learning methods in network neuroscience and neurodegenerative disease subtyping.

Low-dose computed tomography scan and biopsy for assessing lung cancer prevalence and related factors in high-risk populations.

Background: Lung cancer is the second most diagnosed cancer and the leading cause of cancer death in 2020, representing approximately one in 10 (11.4 %) cancers diagnosed and one in 5 (18.0 %) deaths. There are currently very few studies evaluating the prevalence and related factors of lung cancer detected using low-dose CT scans. Objective: Evaluate the prevalence and related factors of lung cancer using low-dose CT scans in high-risk populations in Vietnam. Materials and methods: A cross-sectional analysis study of 169 high-risk patients was conducted to assess the lung cancer prevalence and related factors. Enrolled patients received a physical examination, low-dose computerized tomography scan, and biopsy if abnormalities were found through the CT scan. Univariable and Multivariable analysis through Odd Ratio (OR) to assess the related risk of lung cancer. Results: A total of 169 high-risk patients with a mean age of 62.93 ± 9.31 (years), and the majority were male (91.7 %). Of which 4 cases (2.37 %) were recorded with lung cancer, 3 cases of adenocarcinoma, and 1 case of squamous cell carcinoma. A history of smoking and Chronic Obstructive Pulmonary Disease (COPD) were associated with an increased risk of abnormalities on lung CT scans. Multivariate regression analysis revealed that smoking over 30 pack-years and COPD significantly increased the risk of abnormalities on lung CT scans, p < 0.05.100 % of lung cancer-detected cases were male and smoking ≥30 pack - years. Conclusion: The prevalence of lung cancer in the Vietnamese high-risk population was relatively high. Relative factors such as smoking ≥30 pack - years, and COPD had increased risk of CTscan abnormalities.

Clinical value of the Systemic Inflammatory Response Index for predicting acute pancreatitis severity in Vietnamese setting.

Background and Aim: Accurate prediction of severe acute pancreatitis (SAP) is crucial for timely intervention. This study focuses on the Systemic Inflammatory Response Index (SIRI) to assess its clinical value in predicting the severity of AP in the Vietnamese context. Methods: A cross-sectional prospective study was conducted with acute pancreatitis patients at a national hospital in Ho Chi Minh City. The patients were classified into nonsevere and severe groups, and the clinical characteristics were analyzed. The predictive abilities of SIRI, calculated using neutrophil × monocyte/lymphocyte, was assessed for predictive abilities. Multivariate regression and receiver operating characteristics (ROC) curves evaluated the prognostic factors and predictive accuracy. Results: Among 207 patients, 78.7% had nonsevere AP, and 21.3% had SAP. The severe group exhibited a significantly higher median SIRI (12.0) than the nonsevere group (4.9) (P < 0.001). Multivariate regression identified SIRI (odds ratio [OR] = 1.623) as an independent predictor of SAP. The ROC curve determined a SIRI cutoff of 7.82 with an area under the curve (AUC) of 0.737. Combining the SIRI and Bedside Index for Severity in Acute Pancreatitis (BISAP) score improved the predictive ability (AUC = 0.820) with increased sensitivity (90.91%) (P < 0.001). Conclusion: SIRI, particularly when combined with the BISAP score, shows significant potential to predict SAP severity in the Vietnamese clinical setting, providing valuable information for effective patient management.

Realizing the Tailored Catalytic Performances on Atomic Pt-Promoted Transition Metal Moieties Implanted Layered Double Hydroxides for Water Electrolysis.

High-performance production of green hydrogen gas is necessary to develop renewable energy generation technology and to safeguard the living environment. This study reports a controllable engineering approach to tailor the structure of nickel-layered double hydroxides via doped and absorbed platinum single atoms (PtSA) promoted by low electronegative transition metal (Mn, Fe) moieties (PtSA-Mn,Fe-Ni LDHs). We explore that the electron donation from neighboring transition metal moieties results in the well-adjusted d-band center with the low valence states of PtSA(doped) and PtSA(ads.), thus optimizing adsorption energy to effectively accelerate the H2 release. Meanwhile, a tailored local chemical environment on transition metal centers with unique charge redistribution and high valence states functions as the main center for H2O catalytic dissociation into oxygen. Therefore, the PtSA-Mn,Fe-Ni LDH material possesses a small overpotential of 42 and 288 mV to reach 10 mA·cm-2 for hydrogen and oxygen evolution, respectively, superior to most reported LDH-based catalysts. Additionally, the mass activity of PtSA-Mn,Fe-Ni LDHs proves to be 15.45 times higher than that of commercial Pt-C. The anion exchange membrane electrolyzer stack of PtSA-Mn,Fe-Ni LDHs(+,-) delivers a cell voltage of 1.79 V at 0.5 A·cm-2 and excellent durability over 600 h. This study presents a promising electrocatalyst for a practical water splitting process.

Developmental Disruption of Mef2c in Medial Ganglionic Eminence-derived cortical inhibitory interneurons impairs cellular and circuit function.

BACKGROUND: MEF2C is strongly linked to various neurodevelopmental disorders (NDDs) including autism, intellectual disability, schizophrenia, and attention-deficit/hyperactivity. Mice constitutively lacking one copy of Mef2c, or selectively lacking both copies of Mef2c in cortical excitatory neurons, display a variety of behavioral phenotypes associated with NDDs. The MEF2C protein is a transcription factor necessary for cellular development and synaptic modulation of excitatory neurons. MEF2C is also expressed in a subset of cortical GABAergic inhibitory neurons, but its function in those cell types remains largely unknown. METHODS: Using conditional deletions of the Mef2c gene in mice, we investigated the role of MEF2C in Parvalbumin-expressing Interneurons (PV-INs), the largest subpopulation of cortical GABAergic cells, at two developmental timepoints. We performed slice electrophysiology, in vivo recordings, and behavior assays to test how embryonic and late postnatal loss of MEF2C from GABAergic interneurons impacts their survival and maturation, and alters brain function and behavior. RESULTS: Loss of MEF2C from PV-INs during embryonic, but not late postnatal, development resulted in reduced PV-IN number and failure of PV-INs to molecularly and synaptically mature. In association with these deficits, early loss of MEF2C in GABAergic interneurons lead to abnormal cortical network activity, hyperactive and stereotypic behavior, and impaired cognitive and social behavior. CONCLUSIONS: MEF2C expression is critical for the development of cortical GABAergic interneurons, particularly PV-INs. Embryonic loss of function of MEF2C mediates dysfunction of GABAergic interneurons, leading to altered in vivo patterns of cortical activity and behavioral phenotypes associated with neurodevelopmental disorders.

Automated Cytometric Gating with Human-Level Performance Using Bivariate Segmentation.

Recent advances in cytometry technology have enabled high-throughput data collection with multiple single-cell protein expression measurements. The significant biological and technical variance between samples in cytometry has long posed a formidable challenge during the gating process, especially for the initial gates which deal with unpredictable events, such as debris and technical artifacts. Even with the same experimental machine and protocol, the target population, as well as the cell population that needs to be excluded, may vary across different measurements. To address this challenge and mitigate the labor-intensive manual gating process, we propose a deep learning framework UNITO to rigorously identify the hierarchical cytometric subpopulations. The UNITO framework transformed a cell-level classification task into an image-based semantic segmentation problem. For reproducibility purposes, the framework was applied to three independent cohorts and successfully detected initial gates that were required to identify single cellular events as well as subsequent cell gates. We validated the UNITO framework by comparing its results with previous automated methods and the consensus of at least four experienced immunologists. UNITO outperformed existing automated methods and differed from human consensus by no more than each individual human. Most critically, UNITO framework functions as a fully automated pipeline after training and does not require human hints or prior knowledge. Unlike existing multi-channel classification or clustering pipelines, UNITO can reproduce a similar contour compared to manual gating for each intermediate gating to achieve better interpretability and provide post hoc visual inspection. Beyond acting as a pioneering framework that uses image segmentation to do auto-gating, UNITO gives a fast and interpretable way to assign the cell subtype membership, and the speed of UNITO will not be impacted by the number of cells from each sample. The pre-gating and gating inference takes approximately 2 minutes for each sample using our pre-defined 9 gates system, and it can also adapt to any sequential prediction with different configurations.

Developmental disruption of Mef2c in Medial Ganglionic Eminence-derived cortical inhibitory interneurons impairs cellular and circuit function.

MEF2C is strongly linked to various neurodevelopmental disorders (NDDs) including autism, intellectual disability, schizophrenia, and attention-deficit/hyperactivity. Mice constitutively lacking one copy of Mef2c , or selectively lacking both copies of Mef2c in cortical excitatory neurons, display a variety of behavioral phenotypes associated with NDDs. The MEF2C protein is a transcription factor necessary for cellular development and synaptic modulation of excitatory neurons. MEF2C is also expressed in a subset of cortical GABAergic inhibitory neurons, but its function in those cell types remains largely unknown. Using conditional deletions of the Mef2c gene in mice, we investigated the role of MEF2C in Parvalbumin-expressing Interneurons (PV-INs), the largest subpopulation of cortical GABAergic cells, at two developmental timepoints. We performed slice electrophysiology, in vivo recordings, and behavior assays to test how embryonic and late postnatal loss of MEF2C from GABAergic interneurons impacts their survival and maturation, and alters brain function and behavior. We found that loss of MEF2C from PV-INs during embryonic, but not late postnatal, development resulted in reduced PV-IN number and failure of PV-INs to molecularly and synaptically mature. In association with these deficits, early loss of MEF2C in GABAergic interneurons lead to abnormal cortical network activity, hyperactive and stereotypic behavior, and impaired cognitive and social behavior. Our findings indicate that MEF2C expression is critical for the development of cortical GABAergic interneurons, particularly PV-INs. Embryonic loss of function of MEF2C mediates dysfunction of GABAergic interneurons, leading to altered in vivo patterns of cortical activity and behavioral phenotypes associated with neurodevelopmental disorders.

Ru Single Atom Dispersed on MoS2/MXene for Enhanced Sulfur Reduction Reaction in Lithium-Sulfur Batteries.

The high theoretical energy density (2600 Wh kg-1) and low cost of lithium-sulfur batteries (LSBs) make them an ideal alternative for the next-generation energy storage system. Nevertheless, severe capacity degradation and low sulfur utilization resulting from shuttle effect hinder their commercialization. Herein, Single-atom Ru-doped 1T/2H MoS2 with enriched defects decorates V2C MXene (Ru-MoS2/MXene) produced by a new phase-engineering strategy employed as sulfur host to promote polysulfide adsorption and conversion reaction kinetics. The Ru single atom-doped adjusts the chemical environment of the MoS2/MXene to anchor polysulfide and acts as an efficient center to motivate the redox reaction. In addition, the rich defects of the MoS2 and ternary boundary among 1T/2H MoS2 and V2C accelerate the charge transfer and ion movements for the reaction. As expected, the Ru-MoS2/MXene/S cathode-based cell exhibits a high-rate capability of 684.3 mAh g-1 at 6 C. After 1000 cycles, the Ru-MoS2/MXene/S cell maintains an excellent cycling stability of 696 mAh g-1 at 2 C with a capacity degradation as low as 0.02% per cycle. Despite a high sulfur loading of 9.5 mg cm-2 and a lean electrolyte-to-sulfur ratio of 4.3, the cell achieves a high discharge capacity of 726 mAh g-1.

Effect of AGTR1 A1166C genetic polymorphism on coronary artery lesions and mortality in patients with acute myocardial infarction.

The pathogenesis and prognosis of patients with acute myocardial infarction (AMI) may be influenced by both genetic and environmental factors. Findings on the relationship of polymorphisms in various genes encoding the renin-angiotensin-aldosterone system with coronary artery lesions and mortality in AMI patients are inconsistent. The aim of this study was to determine whether the AGTR1 A1166C genetic polymorphism affects coronary artery lesions and 1-year mortality in post-AMI patients. Patients with their first AMI admitted to Cho Ray Hospital, Vietnam, from January 2020 to August 2021 were enrolled in this prospective clinical study. All participants underwent invasive coronary angiography and were identified as having the genotypes of AGTR1 A1166C by way of a polymerase chain reaction method. All patients were followed up for all-cause mortality 12 months after AMI. The association of the AGTR1 A1166C polymorphism with coronary artery lesions and 1-year mortality was evaluated using logistic regression and Cox regression analysis, respectively. Five hundred and thirty-one AMI patients were recruited. The mean age was 63.9 ± 11.6 years, and 71.6% of the patients were male. There were no significant differences in the location and number of diseased coronary artery branches between the AA and AC+CC genotypes. The AC and CC genotypes were independently associated with ≥ 90% diameter stenosis of the left anterior descending (LAD) artery (odds ratio = 1.940; 95% confidence interval (CI): 1.059-3.552, p = 0.032). The 1-year all-cause mortality rate difference between patients with the AC and CC genotypes versus those with the AA genotype was not statistically significant (hazard ratio = 1.000, 95% CI: 0.429-2.328, p = 1.000). The AGTR1 A1166C genetic polymorphism is associated with very severe luminal stenosis of the LAD but not with mortality in AMI patients.

PaCS-Toolkit: Optimized Software Utilities for Parallel Cascade Selection Molecular Dynamics (PaCS-MD) Simulations and Subsequent Analyses.

Parallel cascade selection molecular dynamics (PaCS-MD) is an enhanced conformational sampling method conducted as a "repetition of time leaps in parallel worlds", comprising cycles of multiple molecular dynamics (MD) simulations performed in parallel and selection of the initial structures of MDs for the next cycle. We developed PaCS-Toolkit, an optimized software utility enabling the use of different MD software and trajectory analysis tools to facilitate the execution of the PaCS-MD simulation and analyze the obtained trajectories, including the preparation for the subsequent construction of the Markov state model. PaCS-Toolkit is coded with Python, is compatible with various computing environments, and allows for easy customization by editing the configuration file and specifying the MD software and analysis tools to be used. We present the software design of PaCS-Toolkit and demonstrate applications of PaCS-MD variations: original targeted PaCS-MD to peptide folding; rmsdPaCS-MD to protein domain motion; and dissociation PaCS-MD to ligand dissociation from adenosine A2A receptor.

The Association between Red Blood Cell Distribution Width and Mortality Risk after Hip Fracture: A Meta-Analysis.

Background and Objectives: Hip fractures in the elderly pose a considerable health risk and cause concern. Red blood cell distribution width (RDW) is a valuable marker for identifying patients at high risk of age-related mortality and various disorders and diseases. However, its association with poor patient outcomes following hip fractures has yet to be fully established. Hence, the purpose of this meta-analysis was to investigate and gain a better understanding of the relationship between RDW levels and the risk of mortality after hip fractures. Materials and Methods: PubMed, Embase, Web of Science, and other databases were comprehensively searched until April 2023 to identify relevant studies. The meta-analysis included observational studies finding the association between RDW at admission or preoperation and short-term and long-term mortality rates following hip fractures. The results were presented in terms of odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results: This meta-analysis included 10 studies involving 5834 patients with hip fractures. Patients with preoperative RDW of over 14.5% had higher risks of 1-year (OR: 5.40, 95% CI: 1.89-15.48, p = 0.002) and 3-month (OR: 2.91, 95% CI: 1.42-5.95, p = 0.004) mortality. Higher admission or preoperative RDW was significantly associated with an 11% higher mortality risk after 1 year (HR: 1.11, 95% CI: 1.06-1.17, p < 0.00001). Patients with higher preoperative RDW had a significantly higher risk of 6-month mortality, which was three times that of those with lower preoperative RDW (OR: 3.00, 95% CI: 1.60-5.61, p = 0.0006). Higher preoperative RDW was correlated to a higher 30-day mortality risk (OR: 6.44, 95% CI: 3.32-12.47, p < 0.00001). Conclusions: Greater RDW values at admission or before surgery were associated with a higher risk of short-term and long-term mortality following hip fractures. Because RDW can be easily measured using a routine blood test at a low cost, this parameter is promising as an indicator of mortality in elderly patients with hip fractures.

A Randomized Noninferiority Trial to Compare Enteral to Parenteral Phosphate Replacement on Biochemistry, Waste, and Environmental Impact and Healthcare Cost in Critically Ill Patients With Mild to Moderate Hypophosphatemia.

OBJECTIVES: Hypophosphatemia occurs frequently. Enteral, rather than IV, phosphate replacement may reduce fluid replacement, cost, and waste. DESIGN: Prospective, randomized, parallel group, noninferiority clinical trial. SETTING: Single center, 42-bed state trauma, medical and surgical ICUs, from April 20, 2022, to July 1, 2022. PATIENTS: Patients with serum phosphate concentration between 0.3 and 0.75 mmol/L. INTERVENTIONS: We randomized patients to either enteral or IV phosphate replacement using electronic medical record-embedded program. MEASUREMENT AND MAIN RESULTS: Our primary outcome was serum phosphate at 24 hours with a noninferiority margin of 0.2 mmol/L. Secondary outcomes included cost savings and environmental waste reduction and additional IV fluid administered. The modified intention-to-treat cohort comprised 131 patients. Baseline phosphate concentrations were similar between the two groups. At 24 hours, mean ( sd ) serum phosphate concentration were enteral 0.89 mmol/L (0.24 mmol/L) and IV 0.82 mmol/L (0.28 mmol/L). This difference was noninferior at the margin of 0.2 mmol/L (difference, 0.07 mmol/L; 95% CI, -0.02 to 0.17 mmol/L). When assigned IV replacement, patients received 408 mL (372 mL) of solvent IV fluid. Compared with IV replacement, the mean cost per patient was ten-fold less with enteral replacement ($3.7 [$4.0] vs. IV: $37.7 [$31.4]; difference = $34.0 [95% CI, $26.3-$41.7]) and weight of waste was less (7.7 g [8.3 g] vs. 217 g [169 g]; difference = 209 g [95% CI, 168-250 g]). C O2 emissions were 60-fold less for comparable phosphate replacement (enteral: 2 g producing 14.2 g and 20 mmol of potassium dihydrogen phosphate producing 843 g of C O2 equivalents). CONCLUSIONS: Enteral phosphate replacement in ICU is noninferior to IV replacement at a margin of 0.2 mmol/L but leads to a substantial reduction in cost and waste.

Triphasic Ni2 P-Ni12 P5 -Ru with Amorphous Interface Engineering Promoted by Co Nano-Surface for Efficient Water Splitting.

This research designs a triphasic Ni2 P-Ni12 P5 -Ru heterostructure with amorphous interface engineering strongly coupled by a cobalt nano-surface (Co@Nim Pn -Ru) to form a hierarchical 3D interconnected architecture. The Co@Nim Pn -Ru material promotes unique reactivities toward hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline media. The material delivers an overpotential of 30 mV for HER at 10 mA cm-2 and 320 mV for OER at 50 mA cm-2 in freshwater. The electrolyzer cell derived from Co@Nim Pn -Ru(+,-) requires a small cell voltage of only 1.43 V in alkaline freshwater or 1.44 V in natural seawater to produce 10 mA cm-2 at a working temperature of 80 °C, along with high performance retention after 76 h. The solar energy-powered electrolyzer system also shows a prospective solar-to-hydrogen conversion efficiency and sufficient durability, confirming its good potential for economic and sustainable hydrogen production. The results are ascribed to the synergistic effects by an exclusive combination of multi-phasic crystalline Ni2 P, Ni12 P5 , and Ru clusters in presence of amorphous phosphate interface attached onto cobalt nano-surface, thereby producing rich exposed active sites with optimized free energy and multi open channels for rapid charge transfer and ion diffusion to promote the reaction kinetics.

Feasibility of Embedding a Randomised Clinical Trial (RCT) into an Electronic Medical Record (EMR) for Patients Admitted to an Intensive Care Unit (ICU).

To establish the feasibility of embedding an RCT into EMR in the ICU, we evaluated the route of phosphate replacement. The EMR screened 207 patients who met the inclusion criteria from 20 April 2022 to 30 June 2022. 162 patients were randomised and 145 patients allocated to treatment. Our study showed that it was feasible to embed screening, randomisation, and treatment allocation for an RCT within an EMR in the ICU.

Truncal Plane Blocks for Implantation of Cardiac Resynchronization Devices: A Systematic Review.

Patients undergoing subcutaneous implantable cardioverter-defibrillator (S-ICD) placement can experience significant perioperative pain. General anesthesia is traditionally used for S-ICD placement and is associated with increased risk. Truncal plane blocks (TPBs) and sedation offer an alternative for adequate analgesia while avoiding hemodynamic compromise related to general anesthesia. A comprehensive evidence search utilized PubMed, CINAHL, Google Scholar, EBSCOhost, US National Library of Medicine Clinical Trials, and Medline Complete databases and the evidence examined the efficacy of TPBs in S-ICD placement. The quality of evidence was assessed using the guidelines described in the Johns Hopkins Nursing Evidence-Based Practice Model. Three randomized-controlled trials, four nonrandomized experimental studies, two nonexperimental studies, and three case studies totaling 379 patients were reviewed. Ultrasound-guided TPBs with sedation demonstrated superior analgesic efficacy for S-ICD procedures. Hemodynamics marginally deviated from baseline values and were well tolerated by patients. The evidence suggests that TPBs provide adequate analgesia during intraoperative and postoperative periods. TPBs are effective in reducing pain scores and opioid consumption postoperatively. Although there were no significant changes in hemodynamic values, more research should be conducted to evaluate the effects on intraoperative hemodynamics.

An Ultra-Flexible Sodium-Ion Full Cell with High Energy/Power Density and Unprecedented Structural Stability.

Futuristic wearable electronics desperately need power sources with similar flexibility and durability. In this regard, the authors, therefore, propose a scalable PAN-PMMA blend-derived electrospinning protocol to fabricate free-standing electrodes comprised of cobalt hexacyanoferrate nanocube cathode and tin metal organic framework-derived nanosphere anode, respectively, for flexible sodium-ion batteries. The resulting unique inter-networked nanofiber mesh offers several advantages such as robust structural stability towards repeated bending and twisting stresses along with appreciable electronic/ionic conductivity retention without any additional post-synthesis processing. The fabricated flexible sodium ion full cells deliver a high working voltage of 3.0 V, an energy density of 273 Wh·kg-1 , and a power density of 2.36 kW·kg-1 . The full cells retain up to 86.73% of the initial capacity after 1000 cycles at a 1.0 C rate. After intensive flexibility tests, the full cells also retain 78.26% and 90.78% of the initial capacity after 1000 bending and twisting cycles (5 mm radius bending and 40o axial twisting), respectively. This work proves that the proposed approach can also be employed to construct similar robust, free-standing nanofiber mesh-based electrodes for mass-producible, ultra-flexible, and durable sodium ion full cells with commercial viability.

Impact of health risk factors on healthcare resource utilization, work-related outcomes and health-related quality of life of Australians: a population-based longitudinal data analysis.

Background: Health risk factors, including smoking, excessive alcohol consumption, overweight, obesity, and insufficient physical activity, are major contributors to many poor health conditions. This study aimed to assess the impact of health risk factors on healthcare resource utilization, work-related outcomes and health-related quality of life (HRQoL) in Australia. Methods: We used two waves of the nationally representative Household, Income, and Labor Dynamics in Australia (HILDA) Survey from 2013 and 2017 for the analysis. Healthcare resource utilization included outpatient visits, hospitalisations, and prescribed medication use. Work-related outcomes were assessed through employment status and sick leave. HRQoL was assessed using the SF-6D scores. Generalized estimating equation (GEE) with logit or log link function and random-effects regression models were used to analyse the longitudinal data on the relationship between health risk factors and the outcomes. The models were adjusted for age, sex, marital status, education background, employment status, equilibrium household income, residential area, country of birth, indigenous status, and socio-economic status. Results: After adjusting for all other health risk factors covariates, physical inactivity had the greatest impact on healthcare resource utilization, work-related outcomes, and HRQoL. Physical inactivity increased the likelihood of outpatient visits (AOR = 1.60, 95% CI = 1.45, 1.76 p < 0.001), hospitalization (AOR = 1.83, 95% CI = 1.66-2.01, p < 0.001), and the probability of taking sick leave (AOR = 1.31, 95% CI = 1.21-1.41, p < 0.001), and decreased the odds of having an above population median HRQoL (AOR = 0.48, 95% CI = 0.45-0.51, p < 0.001) after adjusting for all other health risk factors and covariates. Obesity had the greatest impact on medication use (AOR = 2.02, 95% CI = 1.97-2.29, p < 0.001) after adjusting for all other health risk factors and covariates. Conclusion: Our study contributed to the growing body of literature on the relative impact of health risk factors for healthcare resource utilization, work-related outcomes and HRQoL. Our results suggested that public health interventions aim at improving these risk factors, particularly physical inactivity and obesity, can offer substantial benefits, not only for healthcare resource utilization but also for productivity.

Health-related quality of life in patients with extremity bone sarcoma after surgical treatment: a systematic review.

PURPOSE: We conducted a systematic review of studies reporting on measurement of health-related quality of life (HRQoL), with a special focus on the use of the preference-weighted instruments, in patients with extremity bone sarcoma treated with limb-salvage surgery or amputation. METHODS: We searched MedLine, Embase, Cochrane Library and Web of Science for English-language studies reporting on HRQoL of patients with bone sarcoma from inception to 28 August 2023. All records found were independently reviewed by two reviewers. We used the Newcastle-Ottawa Scale (NOS) and the CONSORT 2010 checklist to assess the quality of the cohort and randomised studies, respectively. RESULTS: The search identified 1225 records, of which 16 studies were included for data extraction. Only one study used a preference-weighted instrument for measuring HRQoL in a small sample of patients (n = 28). Ten studies used the generic SF-36 questionnaire, but no preference-weighted HRQoL based on SF-6D was derived from the SF-36 scores. Most studies comparing HRQoL between amputation and limb-salvage surgery reported no significant differences. Twelve cohort studies scored six or more out of nine points based on the NOS. The only randomised study scored 54% on the CONSORT 2010 checklist. CONCLUSIONS: The approaches used to measure HRQoL were inconsistent and outcome scores varied substantially. Only one study used preference-weighted instruments for HRQoL measurement. Future research into the surgical treatment of extremity bone sarcoma should consider the use of preference-weighted instruments to measure HRQoL, which will therefore enable economic evaluation for the growing orthopaedic armamentarium of novel surgical interventions. REGISTRATION: This systematic review was registered with the PROSPERO International prospective register of systematic reviews (CRD42021282380).

Telehealth in oncology: a cost analysis to evaluate the financial impact of implementing regional trial hubs within a phase 3 cancer clinical trial.

This cost analysis, from a societal perspective, compared the cost difference of a networked teletrial model (NTTM) with four regional hubs versus conventional trial operation at a single metropolitan specialist centre. The Australian phase 3 cancer interventional randomised controlled trial included 152 of 328 regional participants (patient enrolment 2018-2021; 6-month primary end point). The NTTM significantly reduced (AU$2155 per patient) patient travel cost and time and lost productivity.

Shifts in attention drive context-dependent subspace encoding in anterior cingulate cortex during decision making.

Attention is a cognitive faculty that selects part of a larger set of percepts, driven by cues such as stimulus saliency, internal goals or priors. The enhancement of the attended representation and inhibition of distractors have been proposed as potential neural mechanisms driving this selection process. Yet, how attention operates when the cue has to be internally constructed from conflicting stimuli, decision rules, and reward contingencies, is less understood. Here we recorded from populations of neurons in the anterior cingulate cortex (ACC), an area implicated in ongoing error monitoring and correction during decision conflicts, in a challenging attention-shifting task. In this task, mice had to attend to the rewarded modality when presented identical auditory and visual stimuli in two contexts without direct external cues. In the ACC, the irrelevant stimulus continuously became less decodable than the relevant stimulus as the trial progressed to the decision point. This contrasted strongly with our previous findings in V1 where both relevant and irrelevant stimuli were equally decodable throughout the trial. Using analytical tools and a recurrent neural network (RNN) model, we found that the linearly independent representation of stimulus modalities in ACC was well suited to context-gated suppression of a stimulus modality. We demonstrated that the feedback structure of lateral connections in the RNN consisted of excitatory interactions between cell ensembles representing the same modality and mutual inhibition between cell ensembles representing distinct stimulus modalities. Using this RNN model showing signatures of context-gated suppression, we predicted that the level of contextual modulation of individual neurons should be correlated with their relative responsiveness to the two stimulus modalities used in the task. We verified this prediction in recordings from ACC neurons but not from recordings from V1 neurons. Therefore, ACC effectively operates on low-dimensional neuronal subspaces to combine stimulus related information with internal cues to drive actions under conflict.