Miracle-dz/UniFAR-FTUs huggingface dataset:
An Inverse Agonist of Estrogen-Related Receptor Gamma, GSK5182, Enhances Na+/I− Symporter Function in Radioiodine-Refractory Papillary Thyroid Cancer Cells

Previously, we reported that an inverse agonist of estrogen-related receptor gamma (ERRγ), GSK5182, enhances sodium iodide (Na+/I−) symporter (NIS) function through mitogen-activated protein (MAP) kinase signaling in anaplastic thyroid cancer cells. This finding helped us to further investigate the effects of GSK5182 on NIS function in papillary thyroid cancer (PTC) refractory to radioactive iodine (RAI) therapy. Herein, we report the effects of ERRγ on the regulation of NIS function in RAI-resistant PTC cells using GSK5182. RAI-refractory BCPAP cells were treated with GK5182 for 24 h at various concentrations, and radioiodine avidity was determined with or without potassium perchlorate (KClO4) as an NIS inhibitor. We explored the effects of GSK5182 on ERRγ, the mitogen-activated protein (MAP) kinase pathway, and iodide metabolism-related genes. We examined whether the MAP pathway affected GSK5182-mediated NIS function using U0126, a selective MEK inhibitor. A clonogenic assay was performed to evaluate the cytotoxic effects of I-131. GSK5182 induced an increase in radioiodine avidity in a dose-dependent manner, and the enhanced uptake was completely inhibited by KClO4 in BCPAP cells. We found that ERRγ was downregulated and phosphorylated extracellular signal-regulated kinase (ERK)1/2 was upregulated in BCPAP cells, with an increase in total and membranous NIS and iodide metabolism-related genes. MEK inhibitors reversed the increase in radioiodine avidity induced by GSK5182. Clonogenic examination revealed the lowest survival in cells treated with a combination of GSK5182 and I-131 compared to those treated with either GSK518 or I-131 alone. We demonstrate that an inverse agonist of ERRγ, GSK5182, enhances the function of NIS protein via the modulation of ERRγ and MAP kinase signaling, thereby leading to increased responsiveness to radioiodine in RAI-refractory papillary thyroid cancer cells.
Violence against Women during the COVID-19 Pandemic in Mexico

This study measured the prevalence of cases of domestic violence against women and some associated factors during the COVID-19 pandemic in Mexico. Data were collected through a remote survey during 2020. The sample included 47,819 women aged 15 years and older. Jointpoint regression and logistic regression models were used. The prevalence of violence was 11.5%, which decreased in July and subsequently increased. The associated factors were being unemployed (OR = 2.01; 95%CI 1.89–2.16); being partially and totally quarantined (OR = 1.58; 95%CI 1.43–1.75 and OR = 1.47; 95%CI 1.32–1.63); being a caregiver of children; being a caregiver of elderly and/or suffering from a chronic illness (OR = 1.27; 95%CI 1.19–1.36; OR = 1.42; 95%CI 1.33–1.53; OR = 1.59; 95%CI 1.47–1.73); losing a family member to COVID-19 (OR = 1.26; 95%CI 1.13–1.41); and binge drinking (OR = 1.94; 95%CI 1.78–2.12). The confinement measures increased gender inequalities, economic problems and workload which further evidenced violence against women.
The Pursuit of the “Inside” of the Amyloid Hypothesis—Is C99 a Promising Therapeutic Target for Alzheimer’s Disease?

Aducanumab, co-developed by Eisai (Japan) and Biogen (U.S.), has received Food and Drug Administration approval for treating Alzheimer’s disease (AD). In addition, its successor antibody, lecanemab, has been approved. These antibodies target the aggregated form of the small peptide, amyloid-β (Aβ), which accumulates in the patient brain. The “amyloid hypothesis” based therapy that places the aggregation and toxicity of Aβ at the center of the etiology is about to be realized. However, the effects of immunotherapy are still limited, suggesting the need to reconsider this hypothesis. Aβ is produced from a type-I transmembrane protein, Aβ precursor protein (APP). One of the APP metabolites, the 99-amino acids C-terminal fragment (C99, also called βCTF), is a direct precursor of Aβ and accumulates in the AD patient’s brain to demonstrate toxicity independent of Aβ. Conventional drug discovery strategies have focused on Aβ toxicity on the “outside” of the neuron, but C99 accumulation might explain the toxicity on the “inside” of the neuron, which was overlooked in the hypothesis. Furthermore, the common region of C99 and Aβ is a promising target for multifunctional AD drugs. This review aimed to outline the nature, metabolism, and impact of C99 on AD pathogenesis and discuss whether it could be a therapeutic target complementing the amyloid hypothesis.
A Bibliometric Analysis on the Early Works of Dental Anxiety

Dental anxiety has been a common phenomenon under investigation for decades. This report aimed to identify the historical roots of dental anxiety in the research literature. The literature database Web of Science Core Collection was searched to identify relevant papers on this theme. Cited reference analysis on the collected literature set was performed with CRExplorer, a dedicated bibliometric software. This analysis successfully identified the references dealing with dental anxiety in the late 1800s and early 1900s. They included essays that provided expert opinion on dental anxiety, reported semi-structured interviews to elucidate its underlying reasons, introduced psychometric scales to assess dental anxiety, and proposed theories and arguments from psychoanalytic aspects. Several references dealing with anxiety in general were also identified. To conclude, cited reference analysis was useful in revealing the historical origins of dental anxiety research. These cited references provided a concrete foundation to support subsequent dental anxiety research.
Surface Duct Height Distributions for Wallops Island, Virginia, 1985-1994.

Abstract A surface duct is defined as a layer of air adjacent to the earth's surface, in which temperature and humidity gradients cause microwave energy originating within the layer to be sufficiently refracted so that it becomes trapped into propagating along the surface. This layer then acts as a waveguide for microwave propagation and results in propagation beyond the horizon. Failure to consider such conditions may result in erroneous radar meteorological measurements. These ducts can be located by examining refractivity profiles derived from atmospheric measurements. Since 1985, over 3900 profiles of microwave refractivity have been measured using an instrumented helicopter over the Atlantic Ocean off the coast of Wallops Island, Virginia. This helicopter data acquisition system provides higher-resolution measurements than those obtained from radiosondes. This paper presents the heights and associated frequency distributions of surface ducts as determined from these profiles. The year is divided into.
Emission measures, electron densities, and nonthermal velocities from optically thin UV lines near a quiet solar limb.

Calibrated intensities and line widths are presented for 45 optically thin chromospheric and transition-zone UV lines observed in a quiet area near the solar limb. The observations were made over the wavelength range from 1175 to 1915 A with the slit spectrograph on the Skylab Apollo Telescope Mount. Three nonthermal-velocity components are derived from the transition-zone line widths: a main component of 23 km/s and two high-velocity components of 45 and 75 km/s, respectively, which contribute 5% to 10% of the averaged intensity. Absolute intensities are determined as a function of height, emission measures are obtained as functions of height as well as temperature, and electron densities are estimated from density-sensitive line ratios. The densities estimated from different sets of lines are found not to agree with each other, but the values obtained from the Si III multiplet between 1297 and 1301 A are considered to be the most reliable. An atmospheric model with inhomogeneous structures extending high above the solar surface is suggested.
Departure from independence and stationarity in a handball match

This paper analyses direct and indirect forms of dependence in the probability of scoring in a handball match, taking into account the mutual influence of both playing teams. Non-identical distribution (i.d.) and non-stationarity, which are commonly observed in sport games, are studied through the specification of time-varying parameters. The model accounts for the binary character of the dependent variable, and for unobserved heterogeneity. The parameter dynamics is specified by a first-order auto-regressive process. Data from the Handball World Championships 2001–2005 show that the dynamics of handball violate both independence and i.d. , in some cases having a non-stationary behaviour.
Systematic Full-Cycle Engineering Microbial Biofilms to Boost Electricity Production in Shewanella oneidensis

Electroactive biofilm plays a crucial rule in the electron transfer efficiency of microbial electrochemical systems (MES). However, the low ability to form biofilm and the low conductivity of the formed biofilm substantially limit the extracellular electron transfer rate of microbial cells to the electrode surfaces in MES. To promote biofilm formation and enhance biofilm conductivity, we develop synthetic biology approach to systematically engineer Shewanella oneidensis, a model exoelectrogen, via modular manipulation of the full-cycle different stages of biofilm formation, namely, from initial contact, cell adhesion, and biofilm growth stable maturity to cell dispersion. Consequently, the maximum output power density of the engineered biofilm reaches 3.62 ± 0.06 W m−2, 39.3-fold higher than that of the wild-type strain of S. oneidensis, which, to the best our knowledge, is the highest output power density that has ever been reported for the biofilms of the genetically engineered Shewanella strains.
The Value of Current Ante Mortem Meat Inspection and Food Chain Information of Dairy Cows in Relation to Post Mortem Findings and the Protection of Public Health: A Case for a More Risk-Based Meat Inspection

In this study, the contribution of the ante mortem (AM) inspection and the food chain information (FCI) to ensuring meat safety and public health was investigated, by evaluating the slaughterhouse findings of 223,600 slaughtered dairy cows in the Netherlands. The outcome of this study was that the ante mortem (AM) and post mortem (PM) inspections have a substantial overlap, and that with regard to food safety and public health in over 99% of cases the PM could even be omitted on the basis of the AM. In this study, the data provided by the dairy farmers on the current FCI forms contributed little to nothing with regard to the outcomes of AM and PM inspection. It is concluded that current meat inspection procedures need an update and a more risk-based approach needs to be adopted. Regarding this, the AM inspection of dairy cattle should remain, because it plays an important role in ensuring food safety (e.g., by preventing contamination of the slaughter line by excessively dirty animals, or animals with abscesses), monitoring animal welfare and in detecting some important notifiable diseases. The PM inspection, however, could in many cases be omitted, provided there is a strict AM inspection complemented by a vastly improved (automated) way of obtaining reliable FCI.
The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz (RODIN) Trial: Protocol for a Double-Blinded Clinical Trial of Nelonemdaz in Patients with Hyperacute Ischemic Stroke and Endovascular Thrombectomy

Background and Purpose Nelonemdaz (Neu2000) has both selective antagonism against 2B subunit of N-methyl-D-aspartate receptor and antioxidant activity. This drug provides sufficient evidence of neuroprotection in acute cerebral ischemia/reperfusion models. This phase III trial aims to determine this effect in patients. Design The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz is a multicenter, double-blinded clinical trial. A total of 496 patients will be randomly assigned into the nelonemdaz (a total of 5,250 mg divided by 10 times for 5 days) and placebo groups. Patients will be included if they have an acute ischemic stroke (National Institutes of Health Stroke Scale score ≥8) caused by intracranial large vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score ≥4), and if they are expected to undergo endovascular thrombectomy within 12 hours after stroke onset. Endpoints The primary endpoint is a favorable shift in the modified Rankin Scale (mRS) score at 90 days after the first dose of drug. The data will be analyzed by the Cochran–Mantel–Haenszel shift test. The secondary endpoints include functional independence (mRS 0–2) at 35 and 90 days, the favorable shift of mRS at 35 days, the proportion of mRS 0 at 35 and 90 days, and the occurrence rates of symptomatic intracranial hemorrhage within 7 days. Conclusion This trial will clarify the efficacy and safety of nelonemdaz in patients with acute ischemic stroke and endovascular thrombectomy. This study has been registered at ClinicalTrials. gov (NCT05041010).
Slower-X: reduced efficiency of selection in the early stages of X chromosome evolution

Abstract Differentiated X chromosomes are expected to have higher rates of adaptive divergence than autosomes, if new beneficial mutations are recessive (the “faster-X effect”), largely because these mutations are immediately exposed to selection in males. The evolution of X chromosomes after they stop recombining in males, but before they become hemizygous, has not been well explored theoretically. We use the diffusion approximation to infer substitution rates of beneficial and deleterious mutations under such a scenario. Our results show that selection is less efficient on diploid X loci than on autosomal and hemizygous X loci under a wide range of parameters. This “slower-X” effect is stronger for genes affecting primarily (or only) male fitness, and for sexually antagonistic genes. These unusual dynamics suggest that some of the peculiar features of X chromosomes, such as the differential accumulation of genes with sex-specific functions, may start arising earlier than previously appreciated.
Inverse statistical approach in heartbeat time series

We present an investigation on heart cycle time series, using inverse statistical analysis, a concept borrowed from studying turbulence. Using this approach, we studied the distribution of the exit times needed to achieve a predefined level of heart rate alteration. Such analysis uncovers the most likely waiting time needed to reach a certain change in the rate of heart beat. This analysis showed a significant difference between the raw data and shuffled data, when the heart rate accelerates or decelerates to a rare event. We also report that inverse statistical analysis can distinguish between the electrocardiograms taken from healthy volunteers and patients with heart failure.
Radiation damage measurements in room-temperature semiconductor radiation detectors

The literature of radiation damage measurements on cadmium zinc telluride (CZT), cadmium telluride (CT), and mercuric iodide is reviewed and supplemented in the case of CZT by new alpha particle data. CZT strip detectors exposed to intermediate energy proton fluences exhibit increased interstrip leakage after 1010 p/cm2 and significant bulk leakage after 1012 p/cm2. CZT exposed to 200 MeV protons shows a two-fold loss in energy resolution after a fluence of 5 X 109 p/cm2 in thick planar devices but little effect in 2 mm devices. No energy resolution effects were noted from moderated fission spectrum neutrons after fluences up to 1010 n/cm2, although activation was evident. Exposures of CZT to 5 MeV alpha particle at fluences up to 1.5 X 1010 (alpha) /cm2 produced a near linear decrease in peak position with fluence and increases in FWHM beginning at about 7.5 X 109 (alpha) /cm2.
Aligner-D: Leveraging In-DRAM Computing to Accelerate DNA Short Read Alignment

DNA short read alignment task has become a major sequential bottleneck to humongous amounts of data generated by next-generation sequencing platforms. In this paper, an energy-efficient and high-throughput Processing-in-Memory (PIM) accelerator based on DRAM (named Aligner-D) is presented to execute DNA short-read alignment with the state-of-the-art BWT alignment algorithm. We first present the PIM design that utilizes DRAM’s internal high parallelism and throughput. It converts each DRAM array to a potent processing unit for alignment tasks. The proposed Aligner-D can efficiently execute the bulk bit-wise XNOR-based matching operation required by the alignment task with only 3-transistor/col overhead. We then introduce a highly parallel and customized read alignment algorithm based on BWT that supports both exact and inexact match tasks. Next, we present how to map the correlated data of the alignment task to utilize the parallelism from both new hardware and algorithm maximumly. The experimental results demonstrate that Aligner-D obtains <inline-formula> <tex-math notation="LaTeX">$\sim 4\times $ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$\sim 2.45\times $ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$\sim 3.26\times $ </tex-math></inline-formula>, and <inline-formula> <tex-math notation="LaTeX">$\sim 1.65\times $ </tex-math></inline-formula> improvement, respectively, compared with other in-memory computing platforms: Ambit (Seshadri et al., 2017), DRISA-1T1C (Li et al., 2017), DRISA-3T1C (Li et al., 2017), and ReDRAM (Angizi and Fan, 2019). As for DNA short read alignment, Aligner-D boosts the alignment throughput per Watt by <inline-formula> <tex-math notation="LaTeX">$\sim 20104\times $ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$\sim 3522\times $ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$\sim 927\times $ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$\sim 88\times $ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$\sim 5.28\times $ </tex-math></inline-formula>, and <inline-formula> <tex-math notation="LaTeX">$\sim 2.34\times $ </tex-math></inline-formula>, over ReCAM, CPU, GPU, FPGA, Ambit, and DRISA, respectively.
Role of light chain clearance in the recovery of renal function in multiple myeloma: another point of view

ABSTRACT Background Acute kidney injury (AKI) in patients with multiple myeloma (MM) requiring renal replacement treatment (RRT) is associated with high morbidity and mortality. Early reduction of serum free light chains (FLC) using both targeted therapy against MM and intensive hemodialysis (IHD) may improve renal outcomes. We evaluated the effectiveness of two different RRT techniques on renal recovery in an MM patient population: standard dialysis procedure vs IHD with either polymethylmethacrylate (PMMA) or hemodiafiltration with endogenous reinfusion (HFR). Methods This was a multicentric retrospective study with severe AKI related to MM, between 2011 and 2018. Twenty-five consecutive patients with AKI secondary to MM requiring RRT were included. Patients that underwent IHD received six dialysis sessions per week during the first 14 days (PMMA vs HFR). All patients were diagnosed with de novo MM or first relapsed MM. Primary outcome was renal recovery defined as dialysis-free at 6 months follow-up. Results A total of 25 patients were included. Seventeen patients received IHD and eight standard dialysis. All patients were treated with targeted therapy, 84% bortezomib-based. Of the 25 patients included, 14 (56%) became dialysis independent. We observed a higher proportion of patients who received IHD in the group who recovered kidney function compared with those who remained in HD (92.9% vs 36.4%, P = .007). In our study, the use of IHD to remove FLC had a statistically significant association with renal recovery compared with the standard dialysis group (P = .024). Conclusion Early reduction of FLC with IHD as an adjuvant treatment along with MM-targeted therapy may exert a positive impact on renal recovery.
Multialtitude Observations of a Coronal Jet during the Third Whole Sun Month Campaign

On 1999 August 26, a coronal jet occurred at the northwest limb near a sigmoid active region (AR 8668) that was the target for a joint observation plan (SOHO joint observing program 106) during the third Whole Sun Month Campaign. This jet was observed by several instruments at the limb (SOHO/CDS, SOHO/EIT, TRACE, and Mauna Loa Solar Observatory CHIP and PICS) and at 1.64 R☉ (SOHO/UVCS). At the limb, this jet event displayed both low- and high-temperature components. Both high- and low-temperature components were evident during the early phase (first 20 minutes) of the event. However, the low-temperature component is maintained for ~1 hr after the higher temperature component is gone. There is a second brightening (a possible second jet) seen by EIT and TRACE about 50 minutes after the onset of the first jet. The line-of-sight motion at the limb began with a 300 km s-1 redshift and evolved to a 200 km s-1 blueshift. At 1.64 R☉, the intensities of Lyα and Lyβ in the jet increased by a factor of several hundred compared with the background corona. The C III λ977 line also brightened significantly. This indicates low-temperature [~(1-2) × 105 K] emission in the jet, while the intensities of O VI λ1032 and O VI λ1037 increased by as much as a factor of 8. The UVCS data show evidence of heating at the early phase of the event. The Doppler shift in the lines indicates that the line-of-sight (LOS) velocity in the jet started from ~150 km s-1 in blueshift and ended at ~100 km s-1 in redshift. This LOS motion seen at 1.64 R☉ was apparently opposite to what was observed when the jet emerged from the limb. The Doppler dimming analysis indicates that the radial outflow speed correlates with the magnitude of the LOS speed. Interestingly, UVCS observations at 2.33 and 2.66 R☉ show no trace of the jet and SOHO/LASCO observations also yield no firm detection. We find that a simple ballistic model can explain most of the dynamical properties of this jet, while the morphology and the thermal properties agree well with reconnection-driven X-ray jet models.
Monotone Regression and Density Function Estimation at a Point of Discontinuity

Pointwise limit distribution results are given for the isotonic regression estimator at a point of discontinuity. The cases treated are independent data, - and f -mixing data and subordinated Gaussian long range dependent data. Pointwise limit results for the nonparametric maximum likelihood estimator of a monotone density are given at a point of discontinuity, for independent data. The limit distributions are non-standard and differ from the ones obtained for differentiable regression and density functions.
Generalized Lorentz-Lorenz formulas for microstructured materials

In this work the homogenization approach recently proposed in [M. Silveirinha, Phys. Rev. B 75, 115104 (2007)] is applied to derive the analog of the classical Lorentz-Lorenz formula in a generic dielectric crystal, considering the effects of frequency and spatial dispersion. In particular, we obtain a rigorous formula for the interaction constants that relate the local fields with the macroscopic fields and the induced dipole moments, when the response of the particles is described by only the dipole-type terms. To illustrate the application of the results, we homogenize a material formed by plasmonic spheres, demonstrating that the spatial dispersion effects are of crucial importance near the plasmonic resonance.