Miracle-dz/UniFAR-FTUs huggingface dataset:
Accuracy of COVID-19 self-tests with unsupervised nasal or nasal plus oropharyngeal self-sampling in symptomatic individuals in the Omicron period

Background Performances of rapid antigen diagnostic tests (Ag-RDTs) with nasal self-sampling, and oropharyngeal plus nasal (OP-N) self-sampling, in the Omicron period are unknown. Methods Prospective diagnostic accuracy study among 6,497 symptomatic individuals aged [≥]16 years presenting for SARS-CoV-2 testing at three test-sites. Participants were sampled for RT-PCR (reference test) and received one Ag-RDT to perform unsupervised with either nasal self-sampling (during the emergence of Omicron, and after Omicron share was >90%, phase-1) or with OP-N self-sampling (in a subsequent phase-2; Omicron share >99%). The evaluated tests were Acon Flowflex (Flowflex; phase-1 only), MP Biomedicals (MPBio), and Siemens-Healthineers Clinitest (Clinitest). Findings During phase-1, 45% of Flowflex, 29% of MPBio, and 35% of Clinitest participants were confirmatory testers (previously tested positive by a self-test at own initiative). Overall sensitivities with nasal self-sampling were 79.0% (95% CI: 74.7-82.8%) for Flowflex, 69.9% (65.1-74.4%) for MPBio, and 70.2% (65.6-74.5%) for Clinitest. Sensitivities were substantially higher in confirmatory testers (93.6%, 83.6%, and 85.7%, respectively) than in those who tested for other reasons (52.4%, 51.5%, and 49.5%, respectively). Sensitivities decreased by 6.1 (p=0.16 by Chi-square test), 7.0 (p=0.60), and 12.8 (p=0.025) percentage points, respectively, when transitioning from 29% to >95% Omicron. During phase-2, 53% of MPBio, and 44% of Clinitest participants were confirmatory testers. Overall sensitivities with OP-N self-sampling were 83.0% (78.8%-86.7%) for MPBio and 77.3% (72.9%-81.2%) for Clinitest. Comparing OP-N to nasal sampling, sensitivities were slightly higher in confirmatory testers (87.4% and 86.1%, respectively), and substantially higher in those testing for other reasons (69.3% and 59.9%, respectively). Interpretation Sensitivities of three Ag-RDTs with nasal self-sampling decreased during Omicron emergence but was only statistically significant for Clinitest. Sensitivities were substantially influenced by the proportion of confirmatory testers. Addition of oropharyngeal to nasal self-sampling improved sensitivities of MPBio and Clinitest. Funding Dutch Ministry of Health, Welfare, and Sport.
The brain mechanisms of self-identification & self-location in neurosurgical patients using virtual reality and lesion network mapping

Background and Objectives: The identification of cognitive biomarkers in preoperative counselling and their monitoring during brain surgery is of growing interest for the safe conduction of resective intracranial procedures with potential impact on the patients' personality. The conscious experience of identifying with the body (self-identification) and of where ''I'' am in space(self-location) are central for bodily self-consciousness (BSC). In a virtual reality (VR) paradigm using multisensory feedback, illusory self-identification and self-location over a virtual body can be induced, by manipulating the synchrony of visuo-tactile inputs. To date, no studies applied lesion network mapping (LNM) to investigate networks underlying BSC components with VR. Methods: Fifteen neurosurgical patients with intra-axial and extra-axial brain lesions(8 pre-resection, 9 post-resection) performed the visuo-tactile VR paradigm. Patients subjectively rated their self-identification and self-location, after being exposed to synchronous or asynchronous visuo-tactile stimulations. We applied LNM analysis using functional data from 1015 healthy subjects and determined functional connectivity patterns related to each measure. Results: In the post-surgery group, the self-identification network included the right inferior frontal, superior frontal and inferior temporal gyri. The self-location network encompassed the right parahippocampal gyrus, superior temporal gyrus, bilateral cerebellum and brainstem. No clusters survived for the pre-surgery group. Discussion: Our LNM findings reveal the existence of two distinct networks for self-identification and self-location, including structures playing key roles in self-recognition or self-other distinction as well as in spatial navigation or memory processes, respectively. Such networks should be added to the portfolio of presurgical surveillance of functions related to the sense of self to improve future surgical outcomes.
The contribution of white matter pathology, hypoperfusion, lesion load, and stroke recurrence to language deficits following acute subcortical left hemisphere stroke

Aphasia, the loss of language ability following damage to the brain, is among the most disabling and common consequences of stroke. Subcortical stroke, occurring in the basal ganglia, thalamus, and/or deep white matter can result in aphasia, often characterized by word fluency, motor speech output, or sentence generation impairments. The link between greater lesion volume and acute aphasia is well documented, but the independent contributions of lesion location, cortical hypoperfusion, prior stroke, and white matter degeneration (leukoaraiosis) remain unclear, particularly in subcortical aphasia. Thus, we aimed to disentangle the contributions of each factor on language impairments in left hemisphere acute subcortical stroke survivors. Eighty patients with acute left hemisphere subcortical stroke (less than 10 days post-onset) participated. We manually traced acute lesions on diffusion-weighted scans and prior lesions on T2-weighted scans. Leukoaraiosis was rated on T2-weighted scans using the Fazekas et al. (1987) scale. Fluid-attenuated inversion recovery (FLAIR) scans were evaluated for hyperintense vessels in each vascular territory, providing an indirect measure of hypoperfusion in lieu of perfusion-weighted imaging. Compared to subcortical stroke patients without aphasia, patients with aphasia had greater acute and total lesion volume, were older, and had significantly greater damage to the internal capsule (which did not survive controlling for total lesion volume). Patients with aphasia did not differ from non-aphasic patients by other demographic or stroke variables. Age was the only significant predictor of aphasia status in a logistic regression model. Further examination of three participants with severe language impairments suggests that their deficits result from impairment in domain-general, rather than linguistic, processes. Given the variability in language deficits and imaging markers associated with such deficits, it seems likely that subcortical aphasia is a heterogeneous clinical syndrome with distinct causes across individuals.
Effectiveness of shared medical appointments delivered in primary care for improving health outcomes in patients with long-term conditions: a systematic review of randomised controlled trials

Background: Shared medical appointments (SMAs) have the potential to address interlinked challenges of limited capacity in primary healthcare and rising prevalence of patients with multiple long-term conditions (LTCs). This review aimed to examine the effectiveness of SMAs compared to one-to-one appointments in primary care at improving health outcomes and reducing demand on healthcare services. Methods: We searched for randomised controlled trials (RCTs) of SMAs involving patients with LTCs in primary care across six databases from 2013 and added eligible papers identified from previous relevant reviews. Data were extracted and outcomes narratively synthesised, meta-analysis was undertaken where possible. Results: Twenty-three unique trials were included. SMA models varied in terms of components, mode of delivery and target population. Most trials recruited patients with a single LTC, mostly commonly diabetes (n=13), although eight trials selected patients with multiple LTCs. There was substantial heterogeneity in outcome measures which we categorised into health outcomes (biomedical indicators, psychological and well-being measures), behavioural outcomes, and resource use. Meta-analysis showed that participants in SMA groups had lower diastolic blood pressure than those in usual care (d=-0.123, 95%CI = -0.22, -0.03, k=8). No statistically significant differences were found across other outcomes. Where individual studies showed significant differences (patient self-efficacy), these trended in favour of SMAs. Compared with usual care, SMAs had no significant effect on healthcare service use. Conclusions: SMAs were at least as effective as usual care in terms of health outcomes and did not lead to increased healthcare service use in the short-term. They show some potential in improving self-efficacy which may boost self-care. To strengthen the evidence base, future studies should target standardised behavioural and health outcomes and clearly report SMA components so key behavioural ingredients can be identified. Similarly, transparent approaches to measuring costs would improve comparability between studies.
Two-stage classification of electromyogram signals from hand grasps in the transverse plane

Abstract This paper presents a two-stage classification to resolve the effect of arm position changes on electromyogram (EMG) classification for hand grasps in the transverse plane. The proposed method combines the EMG signals with the signals from an inertial measurement unit in both the position and motion classification stages. To improve accuracy, we incorporate EMG data from the upper arm and shoulder with the forearm EMG signals. When evaluated on the five alternative object grasps placed on the nine positions, the proposed technique yields an average total classification error of 0.9%, which is a substantial improvement over the single-stage classification (4.3%).
Targeting DNA polymerase to DNA double-strand breaks reduces DNA deletion size and increases templated insertions generated by CRISPR/Cas9

Abstract Most insertions or deletions generated by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) endonucleases are short (<25 bp), but unpredictable on-target long DNA deletions (>500 bp) can be observed. The possibility of generating long on-target DNA deletions poses safety risks to somatic genome editing and makes the outcomes of genome editing less predictable. Methods for generating refined mutations are desirable but currently unavailable. Here, we show that fusing Escherichia coli DNA polymerase I or the Klenow fragment to Cas9 greatly increases the frequencies of 1-bp deletions and decreases >1-bp deletions or insertions. Importantly, doing so also greatly decreases the generation of long deletions, including those >2 kb. In addition, templated insertions (the insertion of the nucleotide 4 nt upstream of the protospacer adjacent motif) were increased relative to other insertions. Counteracting DNA resection was one of the mechanisms perturbing deletion sizes. Targeting DNA polymerase to double-strand breaks did not increase off-targets or base substitution rates around the cleavage sites, yet increased editing efficiency in primary cells. Our strategy makes it possible to generate refined DNA mutations for improved safety without sacrificing efficiency of genome editing.
A phase II feasibility study of carboplatin and nab‐paclitaxel for advanced non‐small cell lung cancer patients with interstitial lung disease (YLOG0114)

A standard treatment regimen for advanced non‐small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) has not been established since most clinical trials exclude such patients because of the high risk of acute exacerbation of ILD. This study aimed to prospectively investigate the efficacy and safety of carboplatin and nab‐paclitaxel as a first‐line regimen for NSCLC patients with ILD.
Comprehensive evaluation of the test for 5′‐/3′‐end mRNA unbalanced expression as a screening tool for ALK and ROS1 fusions in lung cancer

Despite the progress in the development of next‐generation sequencing (NGS), diagnostic PCR assays remain to be utilized in clinical routine due to their simplicity and low cost. Tests for 5′‐/3′‐end mRNA unbalanced expression can be used for variant‐independent detection of translocations, however, many technical aspects of this methodology require additional investigations.
Biomechanical Role of the Superior Capsule in a Rotator Cuff Sectioned and Repaired State: A Sequential Sectioning Study

Background: Individual contributions of the rotator cuff (RC) and superior capsule (SC) to prevent superior translation of the humerus are not well understood. Purpose: To evaluate the relative contributions of the SC and RC to normal and pathologic shoulder biomechanics by determining their independent effects on superior humeral translation. Study Design: Controlled laboratory study. Methods: Twelve cadaveric shoulders were tested at 0º, 45º, and 90º of abduction under 5 conditions: intact RC/SC, RC sectioned first, SC sectioned first, both structures sectioned, and RC repair. Matched pairs were randomly assigned to the second or third testing condition (RC or SC sectioned first). Specimens were tested under 2 static conditions (40-N deltoid load [balanced load], 80-N deltoid load [superiorly directed load]) and 1 dynamic condition during active abduction. A mixed-design 2-way repeated-measures analysis of variance with Bonferroni adjustments was performed to compare testing conditions. Paired t tests were used to compare specimens in the intact state versus the repaired state. Significance was set at P < . 05. Results: During balanced deltoid loading at 0° and 45º, there was significantly greater humeral translation when both structures were sectioned as compared with the intact state and with both isolated sectioned states (P < .05 for all). No significant differences were observed between or within groups at 90º of abduction. These effects remained consistent with superiorly directed loading. Dynamic testing of both groups showed a significant increase in superior translation for specimens in which the RC was deficient versus the intact state (P = .027), with no difference when the SC was sectioned. The RC repair state returned translation to values similar to the intact state at all abduction angles and loading conditions (P > .05). Conclusion: In this cadaveric study, the SC and RC played an important role in preventing superior humeral translation; however, dynamic testing suggested preferential contribution of the RC. RC repair was effective in preventing superior humeral translation, even with a sectioned SC at the level of the glenohumeral joint. Clinical Relevance: RC repair was effective in preventing superior humeral translation, even in the presence of a sectioned SC at the level of the glenohumeral joint in this cadaveric model. Our data lay the groundwork for future studies investigating the clinical effect of RC repair in an SC sectioned state.
NT‐ProBNP and high‐sensitivity troponin T as screening tests for subclinical chronic heart failure in a general population

The aim of this study was to establish age‐specific and sex‐specific cut‐off values for N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and high‐sensitivity troponin T (hs‐troponin T) in healthy subjects and assess cardiac biomarkers as screening tools for subclinical heart failure (HF) in a general population.
Left thoracoscopic surgery in the prone position for a bronchogenic cyst localized to the lower thoracic esophagus: A case report

A 60‐year‐old woman with an abnormality discovered during a chest X‐ray was referred to the authors' hospital for diagnosis and treatment. Upon enhanced computed tomography (CT), endoscopic ultrasonography, and magnetic resonance imaging, a tumor on the left side of the lower thoracic esophagus was detected. We diagnosed mediastinum cyst. One year after the first visit, a CT examination confirmed an increase in lesion size. Therefore, surgery was performed using a left thoracoscopic approach in the prone position. Before surgery, 3D models were used for simulation. Excision was performed without leakage of the contents. The histopathological diagnosis was a bronchogenic cyst. The left thoracoscopic surgery in the prone position is an uncommon approach but is useful for resecting tumors in the left side of the lower mediastinum. The authors were well‐prepared and able to perform safe and reliable surgery.
SGLT2 Inhibition and Uric Acid Excretion in Patients with Type 2 Diabetes and Normal Kidney Function

Visual Abstract Background and objectives Sodium-glucose transporter 2 (SGLT2) inhibitor–induced uric acid lowering may contribute to kidney-protective effects of the drug class in people with type 2 diabetes. This study investigates mechanisms of plasma uric acid lowering by SGLT2 inhibitors in people with type 2 diabetes with a focus on urate transporter 1. Design, setting, participants, & measurements We conducted an analysis of two randomized clinical trials. First, in the Renoprotective Effects of Dapagliflozin in Type 2 Diabetes study, 44 people with type 2 diabetes were randomized to dapagliflozin or gliclazide for 12 weeks. Plasma uric acid, fractional uric acid excretion, and hemodynamic kidney function were measured in the fasted state and during clamped euglycemia or hyperglycemia. Second, in the Uric Acid Excretion study, ten people with type 2 diabetes received 1 week of empagliflozin, urate transporter 1 blocker benzbromarone, or their combination in a crossover design, and effects on plasma uric acid, fractional uric acid excretion, and 24-hour uric acid excretion were measured. Results In the Renoprotective Effects of Dapagliflozin in Type 2 Diabetes study, compared with the fasted state (5.3±1.1 mg/dl), acute hyperinsulinemia and hyperglycemia significantly reduced plasma uric acid by 0.2±0.3 and 0.4±0.3 mg/dl (both P<0.001) while increasing fractional uric acid excretion (by 3.2%±3.1% and 8.9%±4.5%, respectively; both P<0.001). Dapagliflozin reduced plasma uric acid by 0.8±0.8 during fasting, 1.0±1.0 in hyperinsulinemic-euglycemic state, and 0.8±0.7 mg/dl during hyperglycemic conditions (P<0.001), respectively, whereas fractional uric acid excretion in 24-hour urine increased by 3.0%±2.1% (P<0.001) and 2.6%±4.5% during hyperinsulinemic-euglycemic conditions (P=0.003). Fractional uric acid excretion strongly correlated to fractional glucose excretion (r=0.35; P=0.02). In the Uric Acid Excretion study, empagliflozin and benzbromarone both significantly reduced plasma uric acid and increased fractional uric acid excretion. Effects of combination therapy did not differ from benzbromarone monotherapy. Conclusions In conclusion, SGLT2 inhibitors induce uric acid excretion, which is strongly linked to urinary glucose excretion and is attenuated during concomitant pharmacologic blockade of urate transporter 1. Clinical Trial registry name and registration number: Renoprotective Effects of Dapagliflozin in Type 2 Diabetes (RED), NCT02682563; SGLT2 Inhibition: Uric Acid Excretion Study (UREX), NCT05210517
Investigating possible impact, and interaction, of phytase supplementation during pre-experimental and experimental phases on assay of true phosphorus pre-caecal digestibility and total tract retention

ABSTRACT 1. Two experiments were conducted to investigate whether the use of phytase in the pre-experimental or experimental phases of true pre-caecal phosphorus digestibility (TPD) assay influenced the assayed TPD values. In experiments 1 and 2, broiler chickens were randomly allocated to 12 treatments in a 2 × 2 × 3 factorial arrangement. The factors were pre-experimental phytase supplementation (+ or -), experimental phase phytase supplementation (+ or -) with varying soybean meal inclusion levels (450, 560, or 670 g/kg). 2. The diets in the pre-experimental phase were based on maize-soybean meal, whereas the diet used during the experimental phase was semi-purified, with soybean meal as the only source of P. Both TPD and true phosphorus retention (TPR) were determined using regression for the P output (g/kg, dry matter basis), pre-caecal or total tract, against P intake (g/kg). Data for TPD and TPR were analysed as a 2 × 2 factorial (with or without pre-experimental or experimental phase phytase). 3. In both experiments 1 and 2, there were no significant effects for pre-experimental phytase supplementation nor interaction of pre- and experimental phytase supplementation on any of the pre-caecal digestibility responses. Phytase supplementation during the experimental phase increased (P < 0.01) pre-caecal P digestibility and retention, as well as digestible and retained P intake, and decreased (P < 0.01) P output. 4. In experiment 1, pre- and experimental phytase supplementation increased (P < 0.01) the coefficient of TPR. In experiment 2, there was no significant effect of pre-experimental phytase supplementation on coefficient of pre-caecal TPD. However, phytase supplementation in the experimental phase increased (P < 0.01) the coefficient of pre-caecal TPD. 5. In conclusion, whether or not phytase was supplemented to a P-adequate diet in the pre-experimental phase of the TPD assay, it had no influence on assayed TPD or TPR value.
Arterial Spin Labeling for Pediatric Central Nervous System Diseases: Techniques and Clinical Applications

Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) are techniques used to evaluate brain perfusion using MRI. DSC requires dynamic image acquisition with a rapid administration of gadolinium-based contrast agent. In contrast, ASL obtains brain perfusion information using magnetically labeled blood water as an endogenous tracer. For the evaluation of brain perfusion in pediatric neurological diseases, ASL has a significant advantage compared to DSC, CT, and single-photon emission CT/positron emission tomography because of the lack of radiation exposure and contrast agent administration. However, in ASL, optimization of several parameters, including the type of labeling, image acquisition, background suppression, and postlabeling delay, is required, because they have a significant effect on the quantification of cerebral blood flow (CBF). In this article, we first review recent technical developments of ASL and age-dependent physiological characteristics in pediatric brain perfusion. We then review the clinical implementation of ASL in pediatric neurological diseases, including vascular diseases, brain tumors, acute encephalopathy with biphasic seizure and late reduced diffusion (AESD), and migraine. In moyamoya disease, ASL can be used for brain perfusion and vessel assessment in pre- and post-treatment. In arteriovenous malformations, ASL is sensitive to detect small degrees of shunt. Furthermore, in vascular diseases, the implementation of ASL-based time-resolved MR angiography is described. In neoplasms, ASL-derived CBF has a high diagnostic accuracy for differentiation between low- and high-grade pediatric brain tumors. In AESD and migraine, ASL may allow for accurate early diagnosis and provide pathophysiological information.