Miracle-dz/UniFAR-FTUs huggingface dataset:
Robust GABAergic Regulation of the GnRH Neuron Distal Dendron

Abstract The amino acid transmitter γ-aminobutyric acid (GABA) is suspected to play an important role in regulating the activity of the gonadotropin-releasing hormone (GnRH) neurons controlling fertility. Rodent GnRH neurons have a novel dendritic compartment termed the “distal dendron” through which action potentials pass to the axon terminals and where inputs from the kisspeptin pulse generator drive pulsatile GnRH secretion. Combining Gnrh1-Cre mice with the Cre-dependent calcium sensor GCaMP6 and confocal imaging of acute brain slices, we examined whether GABA regulated intracellular calcium concentrations ([Ca2+]) in the GnRH neuron distal dendron. Short puffs of GABA on the dendron evoked either a monophasic sustained suppression of [Ca2+] or a biphasic acute elevation in [Ca2+] followed by the sustained suppression. Application of muscimol to the dendron replicated the acute elevation in [Ca2+] while baclofen generated the sustained suppression. Robust GABAB receptor-mediated inhibition was observed in 80% to 100% of dendrons recorded from females across the estrous cycle and from approximately 70% of dendrons in males. In contrast, the GABAA receptor–mediated excitation was rare in males and varied across the estrous cycle, being most prominent at proestrus. The activation of GABAB receptors potently suppressed the stimulatory effect of kisspeptin on the dendron. These observations demonstrate that the great majority of GnRH neuron distal dendrons are regulated by GABAergic inputs in a sex- and estrous cycle–dependent manner, with robust GABAB receptor-mediated inhibition being the primary mode of signaling. This provides a new, kisspeptin-independent, pathway for the regulation of pulsatile and surge modes of GnRH secretion in the rodent.
Absorption of Microwave Energy by a Spherical Nonmagnetic Metal Particle

A single particle model is used to provide simple physical insight into the absorption of microwave energy by nonmagnetic metal powders. For this, Mie theory is applied to the microwave heating of a highly conductive spherical particle of micron size. The frequency of the electromagnetic wave is 2.45 GHz. Energy absorption by the highly conductive particle arises from Joule heating by eddy currents which occur as a result of the magnetic component of the electromagnetic wave. Since the electric field component is screened out by conduction electrons, the particle ineffectively couples with this component. The necessary condition for complete separation of dielectric and magnetic losses is provided. Scaling of the induced current with particle size is considered. The region, where the single particle model is valid, is outlined.
Real-world vaccine effectiveness of mRNA vaccines for SARS-CoV-2; a test-negative case-control study in a medium-sized clinic

ABSTRACT Although nationwide immunization with SARS-CoV-2 mRNA vaccines began in February 2021, the evaluation of vaccine effectiveness (VE) using a test-negative design has not been conducted adequately in Japan. To evaluate the effectiveness of the SARS-CoV-2 mRNA vaccines, we conducted a test-negative case–control study during the periods dominated by the Delta and Omicron variants. In total, 518 and 358 adult participants with COVID-19-like symptoms were tested for the virus from August to October 2021 (Delta variant predominance) and in February 2022 (Omicron variant surge), at the Kawasaki Saiwai Clinic. During Delta variant predominance, the effectiveness of full vaccination was 90.4% (95% confidence interval [CI]: 82.1–94.8) and 97.3% (95% CI: 71.7–99.7) against all COVID-19 and moderate-to-severe disease, respectively. However, partial vaccination failed to show effectiveness against moderate-to-severe COVID-19. The effectiveness of the mRNA vaccines against all COVID-19 infection declined to 16.1% (95% CI: −81.0 to 61.1) in February 2022. Our results indicated that, although mRNA vaccines showed significant preventive effects against all COVID-19 during Delta variant predominance, these preventive effects waned during Omicron variant surge. To the best of our knowledge, this is the first study that evaluated VE in the Japanese population during both periods.
Nitrogen abundance in comet Halley

Data on the nitrogen-containing compounds that observed spectroscopically in the coma of Comet Halley are summarized, and the elemental abundance of nitrogen in the Comet Halley nucleus is derived. It is found that 90 percent of elemental nitrogen is in the dust fraction of the coma, while in the gas fraction, most of the nitrogen is contained in NH3 and CN. The elemental nitrogen abundance in the ice component of the nucleus was found to be deficient by a factor of about 75, relative to the solar photosphere, indicating that the chemical partitioning of N2 into NH3 and other nitrogen compounds during the evolution of the solar nebula cannot account completely for the low abundance ratio N2/NH3 = 0.1, observed in the comet. It is suggested that the low N2/NH3 ratio in Comet Halley may be explained simply by physical fractionation and/or thermal diffusion. 88 refs.
Saliva‐based cell‐free DNA and cell‐free mitochondrial DNA in head and neck cancers have promising screening and early detection role

Abstract Background Cell‐free DNA (cfDNA) and cell‐free mitochondrial DNA (cf‐mtDNA) have been postulated as potential diagnostic and prognostic biomarkers for different human malignancies. Early detection of head and neck malignancies is fundamental for optimal patient management. This study, therefore, aimed to assess the utility of saliva‐based liquid biopsy as a noninvasive source of cfDNA and cf‐mtDNA for detecting head and neck cancer (HNSCC). Methods One hundred thirty‐three patients diagnosed with either oral leukoplakia (OLK) or HNSCC were compared with 137 healthy volunteers. An unstimulated whole saliva sample was collected from each participant. The absolute copy numbers of salivary cf‐mtDNA and cfDNA were quantified using Multiplex Quantitative PCR. Two diagnostic indices based on the investigated molecules were assessed for their ability to differentiate between different diagnostic categories. Results The median scores of cfDNA and cf‐mtDNA were statistically significantly higher among HNSCC patients (p < 0.05), revealing area under the curve values of 0.758 and 0.826, respectively. The associated accuracy for this test in discriminating HNSCC from other diagnostic categories was 77.37% for the cfDNA‐based index and 80.5% for the cf‐mtDNA‐based index. The median score of cfDNA was statistically significantly higher for patients with severe epithelial dysplasia (OED) compared to those with epithelial keratosis with no OED and mild OED. However, there was no significant difference between controls and OLK individuals. Conclusion cfDNA and cf‐mtDNA showed potential for use as precision medicine tools to detect HNSCC. Further multi‐centre prospective studies are warranted to assess the prognostic utility of these molecules.
Distributed Event-Triggered Quantized Fault-Tolerant Control of Linear Multiagent Systems With External Disturbances and Parameter Uncertainties

In this article, the issue of fault-tolerant leader-following consensus under a distributed dynamic event-triggered mechanism is addressed for linear multiagent systems (MASs) in the presence of unknown parameter uncertainties, external disturbances, and actuator faults, including loss of effectiveness and bias, in which the mechanism is with quantized state measurements. Due to the fact that information is transmitted via a bandwidth-limited communication network, a quantized control scheme with a uniform quantizer is introduced for leader-following consensus. In order to decrease the communication load and save the limited communication network resources, a distributed event-triggered mechanism is studied for leader-following consensus problem of linear MASs with quantized state measurements. In the presence of actuator faults, external disturbances, and unknown parameter uncertainties, an adaptive coupling gain for the controller is presented. Based on the Lyapunov function approach, the stability of the closed-loop system and the convergence of consensus errors are proved. Furthermore, the Zeno behavior is excluded for the triggering time sequences. Finally, simulation studies are given to verify the effectiveness of the proposed event-triggered fault-tolerant control scheme.
Significance of visual scene‐based learning in the hippocampal systems across mammalian species

The hippocampus and its associated cortical regions in the medial temporal lobe play essential roles when animals form a cognitive map and use it to achieve their goals. As the nature of map‐making involves sampling different local views of the environment and putting them together in a spatially cohesive way, visual scenes are essential ingredients in the formative process of cognitive maps. Visual scenes also serve as important cues during information retrieval from the cognitive map. Research in humans has shown that there are regions in the brain that selectively process scenes and that the hippocampus is involved in scene‐based memory tasks. The neurophysiological correlates of scene‐based information processing in the hippocampus have been reported as “spatial view cells” in nonhuman primates. Like primates, it is widely accepted that rodents also use visual scenes in their background for spatial navigation and other kinds of problems. However, in rodents, it is not until recently that researchers examined the neural correlates of the hippocampus from the perspective of visual scene‐based information processing. With the advent of virtual reality (VR) systems, it has been demonstrated that place cells in the hippocampus exhibit remarkably similar firing correlates in the VR environment compared with that of the real‐world environment. Despite some limitations, the new trend of studying hippocampal functions in a visually controlled environment has the potential to allow investigation of the input–output relationships of network functions and experimental testing of traditional computational predictions more rigorously by providing well‐defined visual stimuli. As scenes are essential for navigation and episodic memory in humans, further investigation of the rodents' hippocampal systems in scene‐based tasks will provide a critical functional link across different mammalian species.
Efficacy and Safety of N-Acetyl-l-Leucine in Children and Adults With GM2 Gangliosidoses

Background and Objectives GM2 gangliosidoses (Tay-Sachs and Sandhoff diseases) are rare, autosomal recessive, neurodegenerative diseases with no available symptomatic or disease-modifying treatments. This clinical trial investigated N-acetyl-l-leucine (NALL), an orally administered, modified amino acid in pediatric (≥6 years) and adult patients with GM2 gangliosidoses. Methods In this phase IIb, multinational, open-label, rater-blinded study (IB1001-202), male and female patients aged ≥6 years with a genetically confirmed diagnosis of GM2 gangliosidoses received orally administered NALL for a 6-week treatment period (4 g/d in patients ≥13 years, weight-tiered doses for patients 6–12 years), followed by a 6-week posttreatment washout period. For the primary Clinical Impression of Change in Severity analysis, patient performance on a predetermined primary anchor test (the 8-Meter Walk Test or the 9-Hole Peg Test) at baseline, after 6 weeks on NALL, and again after a 6-week washout period was videoed and evaluated centrally by blinded raters. Secondary outcomes included assessments of ataxia, clinical global impression, and quality of life. Results Thirty patients between the age of 6 and 55 years were enrolled. Twenty-nine had an on-treatment assessment and were included in the primary modified intention-to-treat analysis. The study met its CI-CS primary end point (mean difference 0.71, SD = 2.09, 90% CI 0.00, 1.50, p = 0.039), as well as secondary measures of ataxia and global impression. NALL was safe and well tolerated, with no serious adverse reactions. Discussion Treatment with NALL was associated with statistically significant and clinically relevant changes in functioning and quality of life in patients with GM2 gangliosidosis. NALL was safe and well tolerated, contributing to an overall favorable risk:benefit profile. NALL is a promising, easily administered (oral) therapeutic option for these rare, debilitating diseases with immense unmet medical needs. Trial Registration Information The trial is registered with ClinicalTrials.gov (NCT03759665; registered on November 30, 2018), EudraCT (2018-004406-25), and DRKS (DRKS00017539). The first patient was enrolled on June 7, 2019. Classification of Evidence This study provides Class IV evidence that NALL improves outcomes for patients with GM2 gangliosidoses.
The significance of a novel inflammatory biomarker, presepsin, in predicting disease prognosis in patients with COVID-19.

OBJECTIVE This study aims at determining the significance of a novel inflammatory biomarker, presepsin, in predicting disease prognosis in patients with COVID-19. PATIENTS AND METHODS This retrospective study was concluded at the University Hospital between April and August 2020. The study involved 88 COVID-19 patients (48 men and 40 women). The patients were categorized into two groups: the patients admitted to the COVID-19 clinic, described as the moderate COVID-19 patients (Group-1; n=44), and those admitted to the internal medicine outpatient clinic, who were the mild COVID-19 patients (Group-2; n=44). The groups were compared using inflammatory markers: presepsin, C-Reactive Protein to Albumin Ratio, Neutrophil to Lymphocyte Ratio, and procalcitonin. RESULTS Serum presepsin levels (195.29 vs. 52.12 pg/ml) were significantly higher in the Group-1 compared to the Group-2 (p=0.001). The gender distribution and average age were similar in both groups (p > 0.05). While ferritin, lactate dehydrogenase, D-Dimer, platelet lymphocyte ratio, C-Reactive Protein to Albumin Ratio (p=0.001), erythrocyte sedimentation ratio, C-Reactive Protein and presepsin were significantly higher in the Group-1 compared to Group-2 (p<0.05), while hemoglobin and lymphocyte were significantly lower in the Group-1 than in Group-2 (p<0.05). CONCLUSIONS Serum presepsin levels were found to be significantly higher in moderate clinical group COVID-19 patients compared to mild group. Presepsin, a new inflammatory biomarker, may be useful in predicting the prognosis and early treatment of COVID-19 infection.
Influence of Equatorial Waves on the Genesis of Super Typhoon Haiyan (2013)

AbstractThe influence of equatorial wave disturbances on the genesis of Super Typhoon Haiyan (2013) is investigated through spectral, composite, and ensemble sensitivity analysis of various observational datasets in combination with predictions from an operational ensemble. Under the favorable large-scale environmental conditions of the Asian monsoon combined with the Madden–Julian oscillation (MJO), the incipient Haiyan develops from a cyclonic disturbance that originates from a train of westward-propagating mixed Rossby–gravity (MRG) waves. Haiyan eventually develops in the monsoon trough region at the leading edge of the moist MJO phase that has strong low-level convergence, high moisture content, and weak shear, along with high sea surface temperature. These favorable environmental conditions promote the intensification of deep moist convection that facilitates the development of the cyclonic disturbance from an MRG wave into a tropical depression, which later intensifies rapidly into Super Typhoon Ha.
Experimental Investigations on Indeterminate-Origin V- and A-Notched Jets

Experimental studies on aspect ratio of 1.5 indeterminate-origin V- and A-notched nozzles using flow visualization and hot-wire anemometry techniques are reported here. Time-sequenced flow visualization images of forced water jets at Reynolds number of 2000 show that the general vortex dynamics of the two nozzle types are largely similar despite the differences in the peak and trough configurations. In addition to vortex lines emanating from both nozzles which result in streamwise vortex pairs forming along both peak and trough locations, consistent bending of the large-scale ring vortices is also observed at some downstream distances away from both nozzle exits, which suggests some limited form of axis-switching behavior
Prognostic and clinicopathological significance of the Prognostic Nutritional Index in patients with gastrointestinal stromal tumours undergoing surgery: a meta-analysis

Objectives Previous studies have investigated the prognostic value of the Prognostic Nutritional Index (PNI) in patients with gastrointestinal stromal tumours (GISTs). However, the results have been inconsistent. We performed a meta-analysis to quantitatively determine the prognostic and clinicopathological significance of PNI in GISTs. Design This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Pooled HRs and 95% CIs were calculated to estimate the prognostic value of PNI in patients with GISTs. Combined ORs and corresponding 95% CIs were used to evaluate the association between the PNI and clinicopathological characteristics. Data sources The electronic databases PubMed, Web of Science, Embase and Cochrane Library were thoroughly searched from inception to December 2021. Eligibility criteria A random-effects model or fixed-effects model was selected based on the level of heterogeneity among the included studies. Results Eight studies comprising 2307 patients were included in this meta-analysis. A low PNI was significantly associated with worse recurrence-free survival (RFS) (HR 2.02, 95% CI 1.66 to 2.47, p<0.001) and overall survival (OS) (HR 4.35, 95% CI 1.25 to 16.83, p=0.033) in patients with GISTs. In addition, a low PNI was significantly associated with tumour size ≥5 cm (OR 1.65, 95% CI 1.21 to 2.24, p=0.002) and primary tumour site in small intestine/colorectum/extra-GISTs (OR 2.03, 95% CI 1.26 to 3.26, p=0.004). Conclusions Patients with GISTs and a lower PNI had inferior RFS and OS. Patients with GISTs and a low PNI may have a higher risk of tumour recurrence.
Collaboration between the Danish and Swedish hernia registers - a study protocol.

INTRODUCTION The most common laparo-endoscopic groin hernia repair techniques are TEP (total extraperitoneal) and TAPP (transabdominal preperitoneal) repair. Despite geographic proximity, Swedish surgeons distinctively favour TEP, whereas Danish surgeons prefer TAPP. The aim of this study is to analyse the risk of reoperation for recurrence after TAPP, TEP and Lichtenstein repair using data from two nationwide registers. We also aim to discuss advantages of international collaboration between nationwide registers. METHODS All groin hernia operations registered as TEP, TAPP or Lichtenstein repair in the Swedish Hernia Register and the Danish Hernia Database between January 2004 and December 2020 will be included. Cumulative hazard rate of reoperation for recurrence will be estimated using Cox-regression analyses adjusted for age and anatomy. CONCLUSION Approximately 400,000 operations are estimated to have been registered prospectively in the inclusion period in the registers. The merging of two nationwide registers was made possible owing to close cooperation between the register steering committees and by obtaining the necessary approvals. This unique collaboration between nationwide registers will make it possible to compare the risk of reoperation for recurrence after TAPP, TEP and Lichtenstein repair on an international level. In future, similar collaboration may be established to explore other outcomes such as complication rates and chronic pain. FUNDING This study protocol is financed by grants generated from Sahlgrenska University Hospital (ALF grant ALFGBG-733561, an agreement concerning research and education of doctors) and the Swedish Society of Medicine (SLS-784551). TRIAL REGISTRATION not relevant.
Spanish-speaking caregivers’ use of referential labels with toddlers is a better predictor of later vocabulary than their use of referential gestures

Variation in how frequently caregivers engage with their children is associated with variation in children’s later language outcomes. One explanation for this link is that caregivers use both verbal behaviors, such as labels, and non-verbal behaviors, such as gestures, to help children establish reference to objects or events in the world. However, few studies have directly explored whether language outcomes are more strongly associated with referential behaviors that are expressed verbally, such as labels, or non-verbally, such as gestures, or whether both are equally predictive. Here, we observed caregivers from 42 Spanish-speaking families in the US engage with their 18-month-old children during 5-min lab-based, play sessions. Children’s language processing speed and vocabulary size were assessed when children were 25 months. Bayesian model comparisons assessed the extent to which the frequencies of caregivers’ referential labels, referential gestures, or labels and gestures together, were more strongly associated with children’s language outcomes than a model with caregiver total words, or overall talkativeness. The best-fitting models showed that children who heard more referential labels at 18 months were faster in language processing and had larger vocabularies at 25 months. Models including gestures, or labels and gestures together, showed weaker fits to the data. Caregivers’ total words predicted children’s language processing speed, but predicted vocabulary size less well. These results suggest that the frequency with which caregivers of 18-month-old children use referential labels, more so than referential gestures, is a critical feature of caregiver verbal engagement that contributes to language processing development and vocabulary growth.
Three-dimensional synchrotron x-ray particle image velocimetry

There is great potential to vastly improve biological flow measurement by using a combination of synchrotron imaging and the latest experimental flow measurement techniques. In the current paper, the three-dimensional velocity field within a cylindrical tube is measured using a combination of phase-contrast x-ray imaging and particle image velocimetry (PIV). We greatly refine the techniques previously used to undertake velocity measurements with a synchrotron light source, substantially enhancing accuracy. Furthermore a PIV correlation peak analysis is developed to allow three-dimensional measurement of the velocity field.
Amplification of Inflammation by Lubricin Deficiency Implicated in Incident, Erosive Gout Independent of Hyperuricemia

In gout, hyperuricemia promotes urate crystal deposition, which stimulates the NLRP3 inflammasome and interleukin‐1β (IL‐1β)–mediated arthritis. Incident gout without background hyperuricemia is rarely reported. To identify hyperuricemia‐independent mechanisms driving gout incidence and progression, we characterized erosive urate crystalline inflammatory arthritis in a young female patient with normouricemia diagnosed as having sufficient and weighted classification criteria for gout according to the American College of Rheumatology (ACR)/EULAR gout classification criteria (the proband).