Miracle-dz/UniFAR-FTUs huggingface dataset:
Developing Economic Models for Assessing the Cost-Effectiveness of Multiple Diagnostic Tests: Methods and Applications

Background Clinical pathways with multiple diagnostic tests are complex to model, but problematic and simplistic approaches are often used in economic evaluations. Methods We analyzed statistical methods of handling multiple diagnostic tests and provided guidance on applying these methods in economic modeling. We first introduced a statistical model to quantify the correlations between 2 tests and how those correlations can be incorporated within an economic model. We also presented the general form of conditional dependence among multiple tests. We then introduced net reclassification improvement (NRI), a measure that evaluates the added value of a new risk factor (e.g., biomarker) for risk prediction. We further provided 2 examples to illustrate the application of these methods. Results Our first example illustrated how to model an add-on test to an existing test, in the absence of a perfect reference standard. After accounting for the imperfect nature of both tests and the conditional dependence between tests, the potential health benefits from the additional test were reduced. This led to differential cost-effectiveness results when comparing models using the perfect test and conditional independence assumptions. The second example illustrated how to evaluate the added value of a new risk factor using the NRI measure. Using the new risk classification provides greater precision in risk prediction, and in the example, the strategy using the new risk classification with treatment for selected individuals led to more favorable cost-effectiveness results. Conclusions These innovative methods for handling multiple diagnostic tests have improved the methodology within the field and should be adopted to provide more accurate estimates within cost-effectiveness analyses. Highlights Economic evaluations of multiple diagnostic tests often apply problematic simplistic approaches, such as ignoring conditional dependence between 2 tests or assuming a perfect final test in the diagnostic pathway. We provided guidance on how to apply improved methods for economic modeling. We introduced methods to model conditional dependence between 2 imperfect tests. We used an example to illustrate how assumptions about perfect diagnostic test accuracy and conditional independence between tests affect cost-effectiveness. Compared with the results of the area under the receiver-operating-characteristic curve, net reclassification improvement has distinct advantages in measuring the added value of a new risk factor for model-based economic evaluation. Economic evaluations that appropriately account for the complexities of diagnostic test pathways can help decision makers ensure efficient use of resources. Graphical Abstract This is a visual representation of the abstract.
Modulation of network centrality and gray matter microstructure using multi‐session brain stimulation and memory training

Neural mechanisms of behavioral improvement induced by repeated transcranial direct current stimulation (tDCS) combined with cognitive training are yet unclear. Previously, we reported behavioral effects of a 3‐day visuospatial memory training with concurrent anodal tDCS over the right temporoparietal cortex in older adults. To investigate intervention‐induced neural alterations we here used functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) datasets available from 35 participants of this previous study, acquired before and after the intervention. To delineate changes in whole‐brain functional network architecture, we employed eigenvector centrality mapping. Gray matter alterations were analyzed using DTI‐derived mean diffusivity (MD). Network centrality in the bilateral posterior temporooccipital cortex was reduced after anodal compared to sham stimulation. This focal effect is indicative of decreased functional connectivity of the brain region underneath the anodal electrode and its left‐hemispheric homolog with other “relevant” (i.e., highly connected) brain regions, thereby providing evidence for reorganizational processes within the brain's network architecture. Examining local MD changes in these clusters, an interaction between stimulation condition and training success indicated a decrease of MD in the right (stimulated) temporooccipital cluster in individuals who showed superior behavioral training benefits. Using a data‐driven whole‐brain network approach, we provide evidence for targeted neuromodulatory effects of a combined tDCS‐and‐training intervention. We show for the first time that gray matter alterations of microstructure (assessed by DTI‐derived MD) may be involved in tDCS‐enhanced cognitive training. Increased knowledge on how combined interventions modulate neural networks in older adults, will help the development of specific therapeutic interventions against age‐associated cognitive decline.
Iliocapsularis: An exploration of the muscle and its omission in education

Anterior hip joint musculature is classically characterized to include iliacus, psoas major, rectus femoris, and sartorius muscles. A lesser‐known muscle, iliocapsularis muscle (ICm), has made infrequent appearances in the literature for the last ~70 years, but potentially has important functional and clinical value. The purpose of this study is to review the historical prevalence of the ICm in peer‐reviewed literature (PRL), further explore the prevalence of the muscle in current anatomical textbooks (ATBs), characterize the muscle with a new series of dissections, assess the muscle's perceived importance to clinicians and educators, and comment on the possible functional significance of the muscle. The ICm was mentioned in 28 peer‐reviewed articles and the muscle was present in 518 of 521 (99%) dissected hips in 13 publications which assessed prevalence. In an audit of 30 recently published ATBs, three texts mentioned the ICm. In 28 anterior hip dissections performed in the current study, the muscle was present in all hips. Anatomy educators were surveyed to determine if the ICm was presently taught in their curricula, and clinicians of various specialties were surveyed regarding their perceptions of the ICm and its clinical relevance. The ICm inclusivity within anatomical curricula from educators reported 8.5%, while 4% of clinicians reported trainees should have an educational background of the ICm. This study confirms that while the ICm is present within PRL, and is ubiquitous amongst human‐donor dissection, the ICm is not mentioned in most ATBs and is absent in the vast majority of anatomical curricula. Lack of inclusion in curricula may lead to a perceived insignificance to currently practicing clinicians despite the potential functional importance at the hip. This discordance suggests that the ICm should be included in ATBs and anatomical curricula so that future clinicians can consider the ICm when evaluating and treating patients.
Strategies and safety considerations of booster vaccination in COVID-19

The first-generation SARS-CoV-2 vaccines have played a significant role in controlling the COVID-19 pandemic, preventing severe diseases, and reducing mortality. However, the continuous emergence of SARS-CoV-2 variants, the persistence of breakthrough infections, and the seemingly rapid decline in the protective efficacy of SARS-CoV-2 vaccines have presented additional challenges for the next phase. There is an urgent need to confirm the necessity of further booster vaccination and combination vaccine approaches. This paper summarizes the latest literature on SARS-CoV-2 variants and vaccine effectiveness and concludes that it is essential to implement booster immunization strategies. Priority should be given to high-risk groups, the elderly, and immunocompromised people. In addition, heterologous vaccination has a longer duration of effect and a broader spectrum than homologous vaccination, making it more conducive to managing the immune escape of SARS-CoV-2 variants.
‘From soil to chocolate bar’: identifying critical steps in the journey of cadmium in a Colombian cacao plantation

Abstract Regulation of maximum levels of cadmium in chocolate is an issue for cacao exportation from many parts of Latin America, including Colombia. These limits are related to the final product, but buyers often request maximum levels of Cd in the beans. However, to date, there is neither a clear understanding of the relationship between the specified levels of Cd in chocolate and cocoa derivatives and levels in harvested beans or soil nor of the effect of post-harvest processes on the levels of Cd in the final product. To address this, the fate of Cd concentration from soil to chocolate bar was followed in a single farm in Santander district, Colombia. The concentration of Cd in soils was measured using ICP-OES and correlated with soil pH, soil organic matter (SOM), and the use of P-based fertilisers. Cd concentrations were also measured in unfermented seeds, fermented and dried beans, shell, nibs, and chocolate. SOM (2.93–3.78%), soil pH (4.7–4.9), soil P concentration (120–132 mg kg−1) affect Cd availability. However, it is still unclear whether Cd concentration of P-based fertilisers (3–30 mg kg−1) is important or not. While post-harvest treatments did not affect the Cd concentration of beans (4.17 ± 0.8 mg kg−1 on average), the removal of the shell (6.57 mg kg−1) from the nibs (3.28 mg kg−1), as well as the percentage of cocoa mass used contributes to a reduction in Cd concentration in the chocolate bar (1.60 mg kg−1). This study provides clear indications on where research into mitigation measures should be focussed, as well as indicating the importance of carrying out analyses for Cd in the nib or cacao mass, rather than the whole bean, reducing Cd concentration by up to 40%. Graphical Abstract
Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism

Abstract Paternal obesity predisposes offspring to metabolic dysfunction, but the underlying mechanisms remain unclear. We investigated whether this metabolic dysfunction is associated with changes in placental vascular development and is fueled by endoplasmic reticulum (ER) stress-mediated changes in fetal hepatic development. We also determined whether paternal obesity indirectly affects the in utero environment by disrupting maternal metabolic adaptations to pregnancy. Male mice fed a standard chow or high fat diet (60%kcal fat) for 8–10 weeks were time-mated with female mice to generate pregnancies and offspring. Glucose tolerance was evaluated in dams at mid-gestation (embryonic day (E) 14.5) and late gestation (E18.5). Hypoxia, angiogenesis, endocrine function, macronutrient transport, and ER stress markers were evaluated in E14.5 and E18.5 placentae and/or fetal livers. Maternal glucose tolerance was assessed at E14.5 and E18.5. Metabolic parameters were assessed in offspring at ∼60 days of age. Paternal obesity did not alter maternal glucose tolerance but induced placental hypoxia and altered placental angiogenic markers, with the most pronounced effects in female placentae. Paternal obesity increased ER stress-related protein levels (ATF6 and PERK) in the fetal liver and altered hepatic expression of gluconeogenic factors at E18.5. Offspring of obese fathers were glucose intolerant and had impaired whole-body energy metabolism, with more pronounced effects in female offspring. Metabolic deficits in offspring due to paternal obesity may be mediated by sex-specific changes in placental vessel structure and integrity that contribute to placental hypoxia and may lead to poor fetal oxygenation and impairments in fetal metabolic signaling pathways in the liver. Summary Sentence Paternal obesity induces placental hypoxia, impairs blood vessel integrity, and is associated with changes in fetal hepatic development, underpinning postnatal metabolic compromised in offspring.
Glomerular filtration rate as a kidney outcome of diabetic kidney disease: a focus on new antidiabetic drugs

Diabetes has reached epidemic proportions, both in Korea and worldwide and is associated with an increased risk of chronic kidney disease and kidney failure (KF). The natural course of kidney function among people with diabetes (especially type 2 diabetes) may be complex in real-world situations. Strong evidence from observational data and clinical trials has demonstrated a consistent association between decreased estimated glomerular filtration rate (eGFR) and subsequent development of hard renal endpoints (such as KF or renal death). The disadvantage of hard renal endpoints is that they require a long follow-up duration. In addition, there are many patients with diabetes whose renal function declines without the appearance of albuminuria, measurement of the eGFR is emphasized. Many studies have used GFR-related parameters, such as its change, decline, or slope, as clinical endpoints for kidney disease progression. In this respect, understanding the trends in GFR changes could be crucial for developing clinical management strategies for the prevention of diabetic complications. This review focuses on the clinical implication of the eGFR-related parameters that have been used so far in diabetic kidney disease. We also discuss the use of recently developed new antidiabetic drugs for kidney protection, with a focus on the GFR as clinical endpoints.
Does Connectedness Need Satisfaction Diminish or Promote Social Goal Striving?

People pursue social goals primarily to satisfy their innate need for affiliation; however, there is no consensus regarding how the successful fulfillment of affiliation need—social connectedness—influences striving for social goals. To address this issue, we proposed a dual-pathway model postulating both a negative effect of social connectedness on social goal striving via decreased emotional distress and a positive effect via increased social self-efficacy. Six studies (total N = 1,849), using cross-sectional, experimental, and daily diary methods, provided support for this model at both the between- and within-person levels. Furthermore, by distinguishing between approach and avoidance social goal strivings, and between deficit-reduction and growth connectedness need orientations, we found that the relative strength with which each path operates differed. The dual-pathway model generates theoretical and practical implications for need satisfaction and goal striving.
Adaption of the Cancer Information Overload Scale for pandemics and assessment of infodemic levels among nurses and midwives

Abstract Aim This study was conducted in three phases. Phase 1 aimed to adapt the Cancer Information Overload Scale and conduct content validity testing. Phase 2 aimed to conduct factorial validity testing of the scale. Phase 3 aimed to assess information overload and the sources of information used by nurses and midwives to keep up‐to‐date about COVID‐19. Design A cross‐sectional survey of nurses and midwives working in a metropolitan Local Health District in Sydney, Australia, was conducted from May to June 2020. Methods Adaptation of the Cancer Information Overload Scale and content validity of the modified scale (as the Pandemic Information Overload Scale) was undertaken by an expert panel comprising of senior nurses and researchers. Factorial validity and reliability of the Pandemic Information Overload Scale were evaluated using exploratory factor analyses using one subsample of the data. Using the second subsample of the data, information overload and sources of information used by nurses and midwives to keep up‐to‐date about COVID‐19 were examined. Results The Pandemic Information Overload Scale is a reliable and valid instrument for measuring information overload among nurses during a pandemic. Its internal consistency was high (α = 0.81, M = 3.84). Conclusion The 8‐item PIO scale is a brief, reliable and psychometrically sound instrument for measuring nurses' and midwives' perceptions of information overload during COVID‐19. Mean scores across this study indicated that participants were experiencing above average information overload. Implementing strategies to reduce this overload would optimize clinical decision making and promote patient safety.
Detecting subject-specific fatigue-related changes in lifting kinematics using a machine learning approach

Abstract Individual responses to fatigue have been observed in lifting kinematics, suggesting a subject-specific approach is necessary for fatigue identification. One-class support vector machines (OCSVM) may provide an objective method to classify fatigue-related kinematic changes during repetitive lifting. Participants completed a repetitive lifting protocol while motion capture recorded lifting motions. Subject-specific kinematics from participants’ first 35% of lifts trained OCSVM decision boundaries. The remaining lifts were separated into test sets and classified against the decision boundary to identify the percentage of outlier lifts within each test set. Spearman’s correlation assessed if the test sets' percentage of outlier lifts increased concurrently with participants’ rating of perceived exertion (RPE). Significant positive associations were found for participants who demonstrated evidence of fatigue, while no significant associations were found for participants who did not demonstrate evidence of fatigue. These results demonstrate the prospective efficacy of an outlier detection tool for fatigue detection during repetitive lifting. Practitioner Summary: An objective subject-specific fatigue detection method is desired for workplace tasks, such as lifting. An outlier detection machine learning approach was identified when lifting movement patterns changed from baseline throughout a repetitive lifting protocol. Participants who demonstrated an increase in outlier movement patterns had a concurrent increase in self-reported fatigue.
Malnutrition and Weight Loss as Prognostic Factors in the Survival of Patients with Gastric Cancer

Abstract Introduction There are limited prospective studies assessing the post-diagnosis nutritional status of patients with gastric cancer (GC). This study aimed to assess the association between nutritional status and three-year survival of patients with GC. Methods In this prospective study, we included all histologically confirmed GC patients admitted to the Imam Reza Hospital in Tabriz, Iran from September 2016 to October 2019. The nutritional status of patients was assessed using the Patient-Generated Subjective Global Assessment (PG-SGA) form. All patients were followed up every six months for three years. The overall survival (OS) was calculated from the diagnosis date to the date of death or last visit. Results In this study, 302 patients (mean age: 67.39 ± 12.04 years) with GC were included. The median OS was 11.00 mo, (95% CI: 80.03, 13.96). Only 28.4% of patients were well-nourished, and survived significantly longer than malnourished patients (20.5 vs. 8 mo, P = 0.01). The mortality hazard rate in patients with moderate and severe malnutrition was 2.04 times higher than well-nourished patients. Conclusion According to our results, the nutrition status of GC patients at the time of diagnosis was independently associated with their survival rate.
Lag screw osteosynthesis of simple olecranon fractures: A biomechanical comparative study

Olecranon fractures are most frequently stabilized by tension band wiring (TBW), which unfortunately leads to relevant implant removal rates due to K-wire migration and soft tissue irritation. As lag screw osteosynthesis (LSO) might be a gentle and effective alternative in simple fracture patterns, the goal of the present study was to biomechanically compare LSO with TBW in simple olecranon fractures at a cadaver model. A simple olecranon fracture (Mayo type IIA) was created in eight pairs of human cadaver elbows, which were pairwise fixed by either TBW or two transcortical 4.0 mm lag screws. Biomechanical testing was conducted as a pulling force, applied to the triceps tendon in a 90° position. First, cyclic loading between 10 and 300 N was performed for 50,000 cycles. Afterward, maximum load was raised by 0.02 N/cycle until construct failure, what was defined as displacement >2 mm. Besides fracture displacement, failure cycle and failure load, the modes of failure were analyzed. Within the first five cycles, there was no significant difference in displacement (median TBW: 0.2 mm; LSO: 0.5 mm; p = 0.091). Both after 2000 (median TBW: 0.2 mm; LSO: 0.6 mm; p = 0.042) and after 20,000 cycles (median TBW: 0.4 mm; LSO: 0.9 mm; p = 0.027), the difference was significant. Failure cycle (median TBW: 72,639 cycles; LSO: 43,429 cycles; p = 0.017) and failure load (median TBW: 702 N; LSO: 303 N; p = 0.025) differed significantly as well. TBW mostly (6/8) failed at the lock of the cerclage wire, whereas most LSO constructs (5/8) failed as a pullout of the proximal fragment. In conclusion, to our biomechanical findings at human cadaver specimens, simple olecranon fractures treated by LSO show higher dislocation rates and lower failure loads compared to conventional TBW and mostly fail by pullout of the proximal fragment.
Gene knockdown of HCN2 ion channels in the ventral tegmental area reduces ethanol consumption in alcohol preferring rats

ABSTRACT Background: Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) ionic channels are known to play a key role in the control of neuron excitability and have been proposed as a molecular target of ethanol. Previous studies in rats have shown that gene-induced overexpression of the HCN2 channel in the ventral tegmental area (VTA) increases the rewarding effects of ethanol and its intake by the animals. Objective: The aim of this work was to study the effects of VTA HCN2 gene knockdown in the voluntary ethanol consumption of alcohol-preferring UChB rats. Methods: Two lentiviral vectors were generated; LV-siRNA-HCN2, coding for a siRNA that elicited >95% reduction of HCN2 protein levels in vitro, and a control vector coding for a scrambled siRNA sequence. Female UChB naïve rats (n = 14) were microinjected into the VTA with LV-siRNA-HCN2 or the scrambled control vector (n = 11). Four days after, animals were given a daily free access to 10% ethanol and water for 10 days. Results: Rats treated with the LV-siRNA-HCN2 vector showed a ~ 70% reduction (p < .001) in their ethanol preference and ethanol intake compared to control animals. No changes were observed in the total fluid intake of both groups. HCN2 levels in the VTA were measured by Western blot showing a reduction of 40% (p < .05) in the rats injected with LV-siRNA-HCN2, compared to control animals. Conclusion: These results show that knockdown of HCN2 ionic channels in the VTA of UChB rats markedly reduces their voluntary ethanol intake, supporting the idea that HCN2 channels may constitute a therapeutic target for alcohol use disorders.
Frictional analysis of deep-groove ball bearings with varying circumference radial preloads

Circumference radial preload due to the interference fit is of a great significant influence on rolling frictional power loss of bearing and service life of machinery. In this article, an analytical method where circumference radial preload is first involved is presented for determining the value of rolling friction power loss of ball bearing (SKF-6205). The experiments under different operating conditions for the bearing were carried out which verify the validity of our proposal. The work described in this article can be regarded as a foundation for the accuracy thermal modeling and friction power loss analysis of the deep-groove ball bearings in machinery.