Miracle-dz/UniFAR-FTUs huggingface dataset:
Is there a safety-net effect with computer-aided detection?

Abstract. Computer-aided detection (CAD) systems are used to aid readers interpreting screening mammograms. An expert reader searches the image initially unaided and then once again with the aid of CAD, which prompts automatically detected suspicious regions. This could lead to a “safety-net” effect, where the initial unaided search of the image is adversely affected by the fact that it is preliminary to an additional search with CAD and may, therefore, be less thorough. To investigate the existence of such an effect, we created a visual search experiment for nonexpert observers mirroring breast screening with CAD. Each observer searched 100 images for microcalcification clusters within synthetic images in both prompted (CAD) and unprompted (no-CAD) conditions. Fifty-two participants were recruited for the study, 48 of whom had their eye movements tracked in real-time; the other 4 participants could not be accurately calibrated, so only behavioral data were collected. In the CAD condition, before prompts were displayed, image coverage was significantly lower than coverage in the no-CAD condition (t47 = 5.29, p < 0.0001). Observer sensitivity was significantly greater for targets marked by CAD than the same targets in the no-CAD condition (t51 = 6.56, p < 0.001). For targets not marked by CAD, there was no significant difference in observer sensitivity in the CAD condition compared with the same targets in the no-CAD condition (t51 = 0.54, p = 0.59). These results suggest that the initial search may be influenced by the subsequent availability of CAD; if so, cross-sectional CAD efficacy studies should account for the effect when estimating benefit.
The Emergence and Early Fate of the Three Rs Concept

In the 60th year since the publication of The Principles of Humane Experimental Technique by W.M.S. Russell and R.L. Burch, we visited the W.M.S. and Claire Russell Archive at the University of Nottingham to discover, or confirm, answers to certain questions: the origins of the UFAW project which led to its writing; the relationship between Russell and Burch; the project plan; the origin of the Three Rs (Replacement, Reduction, Refinement) concept; the drafting, publication and response to the appearance of the book; and the future careers of its authors. We report on our findings, though many other questions have yet to be answered.
The role of minimally invasive hepatectomy for hilar and intrahepatic cholangiocarcinoma: A systematic review of the literature

Despite the fact laparoscopic liver resections (LLR) for cholangiocarcinoma is still limited, this systematic review addressed surgical and oncological outcomes of LLR to treat both perihilar cholangiocarcinoma (pCCA) and intrahepatic cholangiocarcinoma (iCCA). Five comparative and 20 noncomparative studies were found. Regarding iCCA, LLR had lower blood loss and less need for Pringle maneuver. However, open liver resections (OLR) were performed more for major hepatectomies, with better lymphadenectomy rates and higher number of harvested lymph nodes. High heterogeneity and selection bias were suggested for iCCA studies.
Distributed and Parallel ADMM for Structured Nonconvex Optimization Problem

The nonconvex optimization problems have recently attracted significant attention. However, both efficient algorithm and solid theory are still very limited. The difficulty is even pronounced for structured large-scale problems in many real-world applications. This article proposes an application-driven algorithmic framework for structured nonconvex optimization problems with distributed and parallel techniques, which jointly handles the high dimensionality of model parameters and distributed training data. The theoretical convergence of our algorithm is established under moderate assumptions. We apply the proposed method to popular multitask applications, including a multitask reinforcement learning problem. The promising performance demonstrates our framework is effective and efficient.
Excitation and Inhibition Balance Underlying Epileptiform Activity

<italic>Objective:</italic> The phenomenon of postictal generalized EEG suppression state (PGES) — a period with suppressed activity following seizure termination and has been found to be associated with sudden unexpected death in epilepsy — remains poorly understood. This article aims to examine the how the balance of excitation and inhibition (E/I balance) affect the dynamics of seizure and PGES. <italic>Methods:</italic> A network of 1000 Izhikevich model neurons was developed and only the strengths of synaptic connections were adjusted to recreate the dynamics observed in recordings of seizure and PGES from human patients. <italic>Results:</italic> A rapid rise followed by a slow decay of dominant frequency was observed in iEEG recordings of ictal periods and reproduced in the simulated local field potential by changing the E/I balance of the model network. The rate of this dominant frequency evolution was quantified by a single measure, <inline-formula><tex-math notation="LaTeX">$\beta$</tex-math></inline-formula>, which was found to have a significant rank correlation with the duration of PGES in iEEG data and the rate of E/I balance shift in the model. <italic>Significance and Conclusion:</italic> (i) highlighting the importance of E/I balance in the dynamics of seizure and PGES; (ii) suggesting the measure, <inline-formula><tex-math notation="LaTeX">$\beta$</tex-math></inline-formula>, as a marker for PGES and the shift in E/I balance as a neural correlate for this marker.
MRP8/14 and neutrophil elastase for predicting treatment response and occurrence of flare in patients with juvenile idiopathic arthritis

Abstract Objective To study two neutrophil activation markers, myeloid-related protein (MRP) 8/14 and neutrophil elastase (NE), for their ability to predict treatment response and flare in patients with JIA. Methods Using samples from two cohorts (I and II), we determined MRP8/14 and NE levels of 32 (I) and 81 (II) patients with new-onset, DMARD-naïve arthritis and compared patients who responded to treatment (defined as fulfilling ≥ adjusted ACRpedi50 response and/or inactive disease) with non-responders (defined as fulfilling < adjusted ACRpedi50 response and/or active disease) at 6 and 12 months. Secondly, we compared biomarker levels of 54 (I) and 34 (II) patients with clinically inactive disease who did or did not suffer from a flare of arthritis after 6 or 12 months. Receiver operating characteristic analyses were carried out to study the predictive value of MRP8/14 and NE for treatment response and flare. Results For both cohorts, baseline MRP8/14 and NE levels for patients who did or did not respond to treatment were not different. Also, MRP8/14 and NE levels were not different in patients who did or did not flare. Receiver operating characteristic analysis of MRP8/14 and NE demonstrated areas under the curve <0.7 in both cohorts. Conclusion In our cohorts, MRP8/14 and NE could not predict treatment response. Also, when patients had inactive disease, neither marker could predict flares.
Peri‐operative cardiac biomarker screening: a narrative review

Peri‐operative risk estimation has traditionally focused on assessing the likelihood of postoperative morbidity and mortality using pre‐operative functional assessment. Although this strategy is currently recommended by most major society guidelines, contemporary evidence suggests that cardiac biomarker measurement has important advantages over pre‐operative functional assessment. These advantages include superior predictive discrimination and inclusion of the postoperative course in risk estimation. In this review, we provide an overview of the evidence supporting the peri‐operative utilisation, compare risk estimation methods and discuss which patients may benefit most from cardiac biomarker screening. We also discuss protocols for biomarker screening and management of patients with abnormal results.
Trans-Endothelial Insulin Transport is Impaired in Skeletal Muscle Capillaries of Obese Male Mice

Delivery of insulin to the surface of myocytes is required for skeletal muscle (SkM) insulin action. Previous studies have shown that SkM insulin delivery is reduced in the setting of obesity and insulin resistance (IR). The key variables that control SkM insulin delivery are 1) microvascular perfusion and 2) the rate at which insulin moves across the continuous endothelium of SkM capillaries. Obesity and IR are associated with reduced insulin-stimulated SkM perfusion. Whether an impairment in trans-endothelial insulin transport (EIT) contributes to SkM IR, however, is unknown. We hypothesized that EIT would be delayed in a mouse model of diet-induced obesity (DIO) and IR. Using intravital insulin imaging, we found that DIO male mice have a ~15% reduction in EIT compared to their lean counterparts. This impairment in EIT is associated with a 45% reduction in the density of endothelial vesicles. Despite impaired EIT, hyperinsulinemia sustained delivery of insulin to the interstitial space in DIO male mice. Even with maintained interstitial insulin delivery DIO male mice still showed SkM IR, indicating severe myocyellular IR in this model. Interestingly, there was no difference in EIT, endothelial ultrastructure or SkM insulin sensitivity between lean and high fat diet-fed female mice. These results suggest that, in male mice, obesity results in damage to the capillary endothelium which limits the capacity for EIT.
Does exercise intensity affect wellness scores in a dose-like fashion?

Abstract Wellness questionnaires are common in monitoring systems, yet the sensitivity to variations in acute training intensity is unclear. This study examined the controlled dosage effects of differing exercise intensities on wellness variables and subsequent associations with neuromuscular performance. Participants (n = 10) completed low-, moderate- and high-intensity conditions of a 90 min simulated football match shuttle running protocol scaled relative to beep test scores. The protocols were completed in a randomised and counterbalanced fashion matched for time of day. Wellness (sleep quality, readiness to train, soreness, fatigue, stress, mood, motivation) and neuromuscular performance (maximal voluntary contraction, countermovement jump, 6 s cycle-ergometer sprint) were assessed pre-, post- and 24 h post-exercise. Heart rate (HR) and rating of perceived exertion (RPE) were recorded during, and session RPE (sRPE) after exercise. Generalised linear mixed models demonstrated main effects between conditions with increased HR, RPE and sRPE (P < 0.03; d > 0.8) responses from the low-high condition. Total and z-score wellness showed no significant differences between trials at any time-point (P > 0.05; d = 0.03–0.91). Fatigue was lower 24 h post-exercise for the low, compared to moderate and high conditions (P = 0.006–0.047; d = 1.20–1.77). Ratings of fatigue and soreness increased from pre- to 24 h post-trial (P < 0.003; d = 0.96–2.48), while total wellness and readiness to train decreased over time (P < 0.04; d = 0.91–1.86). Wellness showed limited capacity to differentiate training intensities. Practitioners should be aware while wellness may be highly practical, it may be limited to solely determine athlete accommodation of load considering the strength of association observed with the applied load.
DORN1/P2K1 and purino-calcium signalling in plants: making waves with extracellular ATP

Abstract Background and Aims Extracellular ATP governs a range of plant functions, including cell viability, adaptation and cross-kingdom interactions. Key functions of extracellular ATP in leaves and roots may involve an increase in cytosolic free calcium as a second messenger (‘calcium signature’). The main aim here was to determine to what extent leaf and root calcium responses require the DORN1/P2K1 extracellular ATP receptor in Arabidopsis thaliana. The second aim was to test whether extracellular ATP can generate a calcium wave in the root. Methods Leaf and root responses to extracellular ATP were reviewed for their possible links to calcium signalling and DORN1/P2K1. Leaves and roots of wild type and dorn1 plants were tested for cytosolic calcium increase in response to ATP, using aequorin. The spatial abundance of DORN1/P2K1 in the root was estimated using green fluorescent protein. Wild type roots expressing GCaMP3 were used to determine the spatial variation of cytosolic calcium increase in response to extracellular ATP. Key Results Leaf and root ATP-induced calcium signatures differed markedly. The leaf signature was only partially dependent on DORN1/P2K1, while the root signature was fully dependent. The distribution of DORN1/P2K1 in the root supports a key role in the generation of the apical calcium signature. Root apical and sub-apical calcium signatures may operate independently of each other but an apical calcium increase can drive a sub-apical increase, consistent with a calcium wave. Conclusion DORN1 could underpin several calcium-related responses but it may not be the only receptor for extracellular ATP in Arabidopsis. The root has the capacity for a calcium wave, triggered by extracellular ATP at the apex.
Limb‐salvage surgery with vascular reconstruction after lower extremity sarcoma resection: A systematic review and meta‐analysis

Limb‐salvage surgery with vascular reconstruction is the current standard treatment when sarcoma involves major vessels of the lower extremity. However, the low incidence of sarcoma and rarity of limb‐salvage surgery are limiting factors for the reliable study of limb‐salvage surgery. Therefore, a systematic review was conducted to establish better management of lower extremity sarcoma based on currently available evidence.
Lack of full citizenship rights linked to heightened client condom refusal among im/migrant sex workers in Metro Vancouver (2010–2018)

ABSTRACT In Canada, im/migrant sex workers face stigma, health access barriers, and overlapping marginalisation, with end-demand law reforms in 2014 postulated to exacerbate these inequities. Yet, little quantitative evidence on how immigration status shapes HIV/STI risk exists. Drawing on community-based longitudinal cohort data (AESHA, 2010–2018), we used multivariable confounder models with logistic regression to model (1) the independent effect of precarious immigration status (any status revocable under criminal charges: permanent residency/temporary residency/undocumented) on client condom refusal, and (2) the moderating effect of precarious status on the relationship between condom refusal and exposure to end-demand law reform (2015–2018). Over this 8-year study involving 758 sex workers in Metro Vancouver, 16.0% were im/migrants, of whom 57% had precarious immigration status at baseline. 16.5% of participants experienced client condom refusal. Precarious immigration was associated with increased odds of facing condom refusal (adjusted odds ratio [AOR] 2.53, 95% confidence interval [CI] 1.37–4.68), and these odds were heightened post-end-demand law reforms (AOR 4.35, 95%CI 1.21–15.66). Our findings suggest that lack of citizenship rights may enhance barriers to safer sex negotiation and increase HIV/STI risk among sex workers, highlighting the need for sex work and immigration policy reforms.
CRISPR-Cas9/Phosphoproteomics Identifies Multiple Non-canonical Targets of Myosin Light Chain Kinase.

Prior studies have implicated myosin light chain kinase (MLCK) in the regulation of aqua-porin-2 (AQP2) in the renal collecting duct. To discover signaling targets of MLCK, we deleted the Mylk gene to obtain MLCK-null mpkCCD cells and carried out comprehensive phosphopro-teomics using the SILAC method for quantification. Immunocytochemistry and electron microscopy demonstrated a defect in pro-cessing of AQP2-containing early endosomes to late endosomes. The phosphoproteomics experiments revealed that 107 phosphopeptides were changed in abundance by MLCK deletion out of 1743 quantified over multiple replicates (29 decreased and 78 increased). One of the decreased phosphopeptides corresponded to the canonical target site in myosin regulatory light chain. Network analysis indicated that targeted phosphopro-teins clustered into distinct structural/functional groups: "acto-myosin," "signaling," "nuclear envelope," "gene transcription," "mRNA processing," "energy metabolism," "intermediate fila-ments," "adherens junctions," and "tight junctions. " There was significant overlap between the derived MLCK signaling network and a previously determined PKA signaling network. The presence of multiple proteins in the 'acto-myosin' category prompted experiments showing that MLCK deletion inhibits the normal effect of vasopressin to depolymer-ize F-actin, providing a potential explanation for the AQP2 trafficking defect. Changes in phosphorylation of multiple proteins in the nuclear envelope prompted measurement of nuclear size showing a significant increase in average nuclear volume. We conclude that MLCK is part of a multi-component signaling pathway in both cytoplasm and nucleus that includes much more than simple regulation of conven-tional non-muscle myosins through myosin regulatory light chain phosphorylation.
Environmental shedding of toxigenic Clostridioides difficile by asymptomatic carriers: A prospective observational study

Objectives To compare the burden of environmental shedding of toxigenic C. difficile among asymptomatic carriers, C. difficile infected (CDI) patients and non-carriers, in an inpatient non-epidemic setting. Methods C. difficile carriage was determined by positive toxin-B PCR from rectal swabs of asymptomatc patients. Active CDI was defined as a positive 2-step EIA/PCR test in patients with >3 unformed stools/24 hours. C. difficile environmental contamination was assessed by obtaining specimens from 10 sites in the patients’ rooms. Toxigenic strains were identified by PCR. We created a contamination scale to define the overall level of room contamination that ranged from clean to heavy contamination. Results 117 rooms were screened; 70 rooms inhabited by C. difficile carriers, 30 rooms by active CDI patients and 17 rooms by non C. difficile -carriers (Control). In the carrier rooms 29 (41%) had more than residual contamination, from which 17 (24%) were heavily contaminated. In the CDI rooms 12 (40%) had more than residual contamination from which 3 (10%) were heavily contaminated, while in the control rooms, one room (6%) had more than residual contamination and none were heavily contaminated. In a multivariate analysis, the contamination score of rooms inhabited by carriers did not differ from rooms of CDI patients, yet both were significantly more contaminated than those of none carriers OR 12.23 and 11.16 (95%CI:1.5-99.96 P=0.0195, and 1.19-104.49 p=0.035), respectively. Conclusion Here we show that C. difficile carriers’ rooms are as contaminated as those of patients with active CDI and significantly more than those of non-carriers.
Body composition in very preterm infants before discharge is associated with macronutrient intake.

Very preterm infants experience poor postnatal growth relative to intrauterine growth rates but have increased %body fat (%fat). The aim of this study was to identify nutritional and other clinical predictors of infant %fat, fat mass (g) and lean mass (g) in very preterm infants during their hospital stay. Daily intakes of protein, carbohydrate, lipids and energy were recorded from birth to 34weeks postmenstrual age (PMA) in 50 infants born <32weeks. Clinical illness variables and anthropometric data were also collected. Body composition was assessed at 34-37weeks PMA using the PEA POD Infant Body Composition System. Multiple regression analysis was used to identify independent predictors of body composition (%fat, fat mass or lean mass). Birthweight, birthweight z-score and PMA were strong positive predictors of infant lean mass. After adjustment for these factors, the strongest nutrient predictors of lean mass were protein:carbohydrate ratios (102 - 318g lean mass/0.1 increase in ratio, P=0.006-0.015). Postnatal age and PMA were the strongest predictors of infant fat mass or %fat. When postnatal age and PMA were accounted for a higher intake of energy (-5.90 to -6.75 gFM/kCal/kg/d, P=0.001-0.012), protein (-75.5 to -81.0 gFM/g/kg/d, P=0.019-0.038) and carbohydrate (-27.2 to -30.0 gFM/g/kg/d, P=0.012-0.019) was associated with a lower fat mass at 34-37 weeks PMA. Higher intakes of energy, protein and carbohydrate may reduce fat accumulation in very preterm infants until at least 34-37 weeks PMA.
Influence of propofol‐based total intravenous anaesthesia on peri‐operative outcome measures: a narrative review

Propofol‐based total intravenous anaesthesia is well known for its smooth, clear‐headed recovery and anti‐emetic properties, but there are also many lesser known beneficial properties that can potentially influence surgical outcome. We will discuss the anti‐oxidant, anti‐inflammatory and immunomodulatory effects of propofol and their roles in pain, organ protection and immunity. We will also discuss the use of propofol in cancer surgery, neurosurgery and older patients.
Increased Support for Same-sex Marriage in the US: Disentangling Age, Period, and Cohort Effects

ABSTRACT Previous research established a substantial increase in support for same-sex marriage in the US, but it is unclear if this increase is due to cohort (a change that affects only the younger generation) or time period (a change that affects those of all ages). In a nationally representative sample of American adults (n = 13,483) in 1988 and 2004–2018, increased support for same-sex marriage was primarily due to time period (from 11.1% in 1988 to 66.7% in 2018). There was a smaller cohort effect, with a fairly linear increase between cohorts born in the 1960s and those born in the 1990s. Time period increases in support for same-sex marriage appeared among across gender, race, education levels, regions, and levels of religious service attendance, though differences in support still remain. The results suggest Americans of all ages modified their beliefs about same-sex marriage over time.
Cognitive-Behavioral Interventions for Gastrectomy Patients with the Early Stage of Gastric Cancer

The aim of this study was to evaluate the effect of cognitive behavior therapy for self-efficacy and psychological stress. The study subjects were gastrectomy patients with the early stage of gastric cancer, and interventions comprised of weekly counseling and journal writing. Conceptual framework of this study was based on Lazarus's Stress model (1984), and for the framework for Self-efficacy is based on the Social Learning Theory (Bandura, 1977, 1986). Three scales were employed to evaluate the effect of interventions: general self-efficacy (GSES: Sakano and Toujyou, 1986), mental stress response (SRS-18: Suzuki et al., 1997), and moods (DAMS: Fukui, 1997). Subjects were allocated to either intervention group (IG (n=14)) or to control group (CG (n= 12))and of those twenty completed the study (9 and 11, respectively). Subjects were assessed at baseline, at the time of discharge, and 1 month after discharge . Results: 1)Two sample t test revealed that IG had significantly lower SRS-18 total scores and SRS-18 subscale (depression-anxiety) scores than CG did at discharge. One month after discharge , depression-anxiety scores for IG remained significantly lower than that for CG (p<0.05). 2)Split Plot Design Repeated Measure ANOVA revealed that DAMS subscale scores (positive *1 大阪大学大学院医学系研究科保健学専攻博士後期課程 *2 大阪大学医学部保健学科 -1-