Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of SLC20A2 deletions in patients with primary familial brain calcification

Primary familial brain calcification (PFBC) is a rare neurological disorder. Mutations in five genes (SLC20A2, PDGFRB, PDGFB, XPR1, and MYORG) have been linked to PFBC. Here, we used SYBR green‐based real‐time quantitative polymerase chain reaction (PCR) assay and denaturing high‐performance liquid chromatography analysis to detect copy number variants (CNVs) in 20 unrelated patients with PFBC, negatively sequenced for the five known genes. We identified three deletions in SLC20A2, including a large de novo full gene deletion and two exonic deletions confined to exon 2 and exon 6, respectively. Subsequent linked‐read whole‐genome sequencing of the patient with the large deletion showed a 1.7 Mb heterozygous deletion which removed the entire coding regions of SLC20A2 as well as 21 other genes. In the family with a deletion of exon 6, a missense variant of uncertain significance (SLC20A2: p.E267Q) also co‐segregated with the disease. Functional assay showed the deletion could result in significantly impaired phosphate transport, whereas the p.E267Q variant did not. Our results confirm that deletion in SLC20A2 is a causal mechanism for PFBC and highlight the importance of functional study for classifying a rare missense variant as (likely) pathogenic.
Ablation of elongation factor 2 kinase enhances heat-shock protein 90 chaperone expression and protects cells under proteotoxic stress

Eukaryotic elongation factor 2 kinase (eEF2K) negatively regulates the elongation stage of mRNA translation and is activated under different stress conditions to slow down protein synthesis. One effect of eEF2K is to alter the repertoire of expressed proteins, perhaps to aid survival of stressed cells. Here, we applied pulsed stable isotope labeling with amino acids in cell culture (SILAC) to study changes in the synthesis of specific proteins in human lung adenocarcinoma (A549) cells in which eEF2K had been depleted by an inducible shRNA. We discovered that levels of heat-shock protein 90 (HSP90) are increased in eEF2K-depleted human cells as well as in eEF2K-knockout (eEF2K−/−) mouse embryonic fibroblasts (MEFs). This rise in HSP90 coincided with an increase in the fraction of HSP90 mRNAs associated with translationally active polysomes, irrespective of unchanged total HSP90 levels. These results indicate that blocking eEF2K function can enhance expression of HSP90 chaperones. In eEF2K−/− mouse embryonic fibroblasts (MEFs), inhibition of HSP90 by its specific inhibitor AUY922 promoted the accumulation of ubiquitinated proteins. Notably, HSP90 inhibition promoted apoptosis of eEF2K−/− MEFs under proteostatic stress induced by the proteasome inhibitor MG132. Up-regulation of HSP90 likely protects cells from protein folding stress, arising, for example, from faster rates of polypeptide synthesis due to the lack of eEF2K. Our findings indicate that eEF2K and HSPs closely cooperate to maintain proper proteostasis and suggest that concomitant inhibition of HSP90 and eEF2K could be a strategy to decrease cancer cell survival.
Sensitivity to the two peptide bacteriocin plantaricin EF is dependent on CorC, a membrane‐bound, magnesium/cobalt efflux protein

Lactic acid bacteria produce a variety of antimicrobial peptides known as bacteriocins. Most bacteriocins are understood to kill sensitive bacteria through receptor‐mediated disruptions. Here, we report on the identification of the Lactobacillus plantarum plantaricin EF (PlnEF) receptor. Spontaneous PlnEF‐resistant mutants of the PlnEF‐indicator strain L. plantarum NCIMB 700965 (LP965) were isolated and confirmed to maintain cellular ATP levels in the presence of PlnEF. Genome comparisons resulted in the identification of a single mutated gene annotated as the membrane‐bound, magnesium/cobalt efflux protein CorC. All isolates contained a valine (V) at position 334 instead of a glycine (G) in a cysteine‐β‐synthase domain at the C‐terminal region of CorC. In silico template‐based modeling of this domain indicated that the mutation resides in a loop between two β‐strands. The relationship between PlnEF, CorC, and metal homeostasis was supported by the finding that PlnEF‐resistance was lost when PlnEF was applied together with high concentrations of Mg2+, Co2+, Zn2+, or Cu2+. Lastly, PlnEF sensitivity was increased upon heterologous expression of LP965 corC but not the G334V CorC mutant in the PlnEF‐resistant strain Lactobacillus casei BL23. These results show that PlnEF kills sensitive bacteria by targeting CorC.
The surface composition of asteroid 162173 Ryugu from Hayabusa2 near-infrared spectroscopy

Hayabusa2 at the asteroid Ryugu Asteroids fall to Earth in the form of meteorites, but these provide little information about their origins. The Japanese mission Hayabusa2 is designed to collect samples directly from the surface of an asteroid and return them to Earth for laboratory analysis. Three papers in this issue describe the Hayabusa2 team's study of the near-Earth carbonaceous asteroid 162173 Ryugu, at which the spacecraft arrived in June 2018 (see the Perspective by Wurm). Watanabe et al. measured the asteroid's mass, shape, and density, showing that it is a “rubble pile” of loose rocks, formed into a spinning-top shape during a prior period of rapid spin. They also identified suitable landing sites for sample collection. Kitazato et al. used near-infrared spectroscopy to find ubiquitous hydrated minerals on the surface and compared Ryugu with known types of carbonaceous meteorite. Sugita et al. describe Ryugu's geological features and surface colors and combined results from all three papers to constrain the asteroid's formation process. Ryugu probably formed by reaccumulation of rubble ejected by impact from a larger asteroid. These results provide necessary context to understand the samples collected by Hayabusa2, which are expected to arrive on Earth in December 2020. Science, this issue p. 268, p. 272, p. 252; see also p. 230 Near-Earth asteroid Ryugu’s surface is dark and partially hydrated, similar to heat-processed carbonaceous meteorites. The near-Earth asteroid 162173 Ryugu, the target of the Hayabusa2 sample-return mission, is thought to be a primitive carbonaceous object. We report reflectance spectra of Ryugu’s surface acquired with the Near-Infrared Spectrometer (NIRS3) on Hayabusa2, to provide direct measurements of the surface composition and geological context for the returned samples. A weak, narrow absorption feature centered at 2.72 micrometers was detected across the entire observed surface, indicating that hydroxyl (OH)–bearing minerals are ubiquitous there. The intensity of the OH feature and low albedo are similar to thermally and/or shock-metamorphosed carbonaceous chondrite meteorites. There are few variations in the OH-band position, which is consistent with Ryugu being a compositionally homogeneous rubble-pile object generated from impact fragments of an undifferentiated aqueously altered parent body.
Effects of extremely low-frequency electromagnetic fields on B16F10 cancer cells

ABSTRACT This paper presents a method to inhibit B16F10 cancer cells using extremely low-frequency electromagnetic fields (ELF-EMFs) and to evaluate cell viability using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The study examined the effect of a natural EMF resonance frequency (7.83 Hz) and a power line frequency (60 Hz) on B16F10 cancer cells for 24 and 48 h. The B16F10 cancer cells were also exposed to sweep frequencies in several sweep intervals to quantitatively analyze the viability of cancer cells. The results yielded a 17% inhibition rate under 7.83 Hz compared with that of the control group. Moreover, sweep frequencies in narrow intervals (7.83 ± 0.1 Hz for the step 0.05 Hz) caused an inhibition rate of 26.4%, and inhibitory effects decreased as frequency sweep intervals increased. These results indicate that a Schumann resonance frequency of 7.83 Hz can inhibit the growth of cancer cells and that using a specific frequency type can lead to more effective growth inhibition.
Measures of speeding from a GPS-based travel behavior survey

Abstract Objective: Lacking information about actual driving speed on most roads in the Minneapolis–St. Paul region, we determine car speeds using observations from a Global Positioning System (GPS)-based travel survey. Speed of travel determines the likelihood and consequences of collisions. We identify the road segments where speeding occurs. This article then analyzes the relationship between link length, traveler characteristics, and speeding using GPS data collected from 152 individuals over a 7-day period as part of the Minneapolis–St. Paul Travel Behavior Inventory. Methods: To investigate the relationship, we employed an algorithm and process to accurately match the GPS data with geographic information system (GIS) databases. Comparing actual travel speed from GPS data with posted speed limits, we measure where and when speeding occurs and by whom. We posit that link length and demographics shape the decision to speed. Results: Speeding is widespread under both high speed limits (e.g., 60 mph [97 km/h]) and low speed limits (less than 25 mph [40 km/h]); in contrast, speeding is less common at 30–35 mph (48–56 km/h). The results suggest that driving patterns depend on the road type. We also find that when there are many intersections, the average link speed (and speeding) drops. Long links are conducive to speeding. Younger drivers and more educated drivers also speed more, and speeding occurs more often in the evening. Conclusions: Road design and link length (or its converse, frequency of intersections) affect the likelihood of speeding. Use of increasingly available GPS data allows more systematic empirical analysis of designs and topologies that are conducive to road safety.
Effects of Magnesium Deficiency on Mechanisms of Insulin Resistance in Type 2 Diabetes: Focusing on the Processes of Insulin Secretion and Signaling

Magnesium (Mg2+) is an essential mineral for human health and plays an important role in the regulation of glucose homeostasis and insulin actions. Despite the widespread clinical evidences for the association of Mg2+ deficiency (MgD) and type 2 diabetes mellitus (T2D), molecular mechanisms by which Mg2+ contributes to insulin resistance (IR) are still under discussion. Mg2+ regulates electrical activity and insulin secretion in pancreatic beta-cells. Intracellular Mg2+ concentrations are critical for the phosphorylation of the insulin receptor and other downstream signal kinases of the target cells. Low Mg2+ levels result in a defective tyrosine kinase activity, post-receptor impairment in insulin action, altered cellular glucose transport, and decreased cellular glucose utilization, which promotes peripheral IR in T2D. MgD triggers chronic systemic inflammation that also potentiates IR. People with T2D may end up in a vicious circle in which MgD increases IR and IR causes MgD, that requires periodic monitoring of serum Mg2+ levels.
A Patch/Dipole Hybrid-Mode Antenna for Sub-6GHz Communication

A low-profile antenna with a high gain and broad bandwidth is proposed for Sub-6GHz communication in this paper. A narrow-band patch mode and a narrow-band dipole mode are shared in one radiator and simultaneously excited to broaden the bandwidth. A compact prototype with a projection size of 0.90 λ0 × 0.78 λ0 and a profile of 0.13 λ0 (λ0 is the wavelength in the free space at the center of the operating frequency) is fabricated and measured. The measurement demonstrates an impedance bandwidth of 67.50%, covering the frequency range from 2.75 GHz to 5.45 GHz and an average gain of 8.4 dBi in the operating band of 3.0–5.0 GHz.
Rates of Cardiac Rhythm Abnormalities in Patients with CKD and Diabetes.

BACKGROUND AND OBJECTIVES Cardiac arrhythmias increase mortality and morbidity in CKD. We evaluated the rates of subclinical arrhythmias in a population with type 2 diabetes and patients with moderate to severe CKD who were not on dialysis. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS This is a prospective observational study, using continuous ambulatory cardiac monitors to determine the rate of atrial and ventricular arrhythmias, as well as conduction abnormalities in this group. RESULTS A total of 38 patients (34% women), with mean eGFR of 38±13 ml/min per 1.73 m2, underwent ambulatory cardiac monitoring for 11.2±3.9 days. The overall mean rate of any cardiac arrhythmia was 88.8 (95% confidence interval [95% CI], 27.1 to 184.6) episodes per person-year (PY). A history of cardiovascular disease was associated with a higher rate of detected arrhythmia (rate ratio, 5.87; 95% CI, 1.37 to 25.21; P<0.001). The most common arrhythmia was atrial fibrillation, which was observed in two participants with known atrial fibrillation and was a new diagnosis in four patients (11%), none of whom experienced symptoms. Overall, atrial fibrillation episodes occurred at a rate of 37.6 (95% CI, 2.4 to 112.3) per PY. Conduction abnormalities were found in eight patients (21%), a rate of 26.5 (95% CI, 4.2 to 65.5) per PY. Rates of ventricular arrhythmias were low (14.5 per PY; 95% CI, 4.3 to 32.0) and driven by premature ventricular contractions. CONCLUSIONS Cardiac rhythm abnormalities are common in patients with diabetes with moderate to severe CKD not requiring dialysis. Rates of atrial fibrillation are high and episodes are asymptomatic. Future studies are needed to determine the role of screening and upstream therapy of cardiac arrhythmias in this group.
Perinatal outcome of pregnancy after adenomyomectomy: summary of 10 cases with a brief literature review

Abstract Objectives: The purpose of this study was the perinatal outcomes of patients who became pregnant after adenomyomectomy. Study design: The retrospective cohort study was performed involving pregnant women with a history of adenomyomectomy between 1 January 2011 and 31 December 2018. At 24–26 weeks, the patients were admitted even without symptoms or signs. When regular uterine contractions were observed, tocolysis was performed. Results: Ten patients were included. Elective and emergent cesarean section (CS) was performed in seven and three patients, respectively. Emergent CS was performed due to onset of labor (tocolytic failure) at 28, 24, and 32 weeks. Although no patients suffered uterine rupture, myometrial thinning was observed at the site corresponding to that of adenomyomectomy in three patients. Of these three patients, two required emergent CS due to tocolytic failure with cervical length (CL) shortening. In contrast, CLs were stable in the other seven patients with elective CS. Conclusions: Three patients after adenomyomectomy showed preterm delivery, and three had a very thin uterus to the extent that the fetus could be observed through the uterine wall. A short CL should be paid special attention in pregnant women with a history of adenomyomectomy.
CD47-Targeted Near-Infrared Photoimmunotherapy for Human Bladder Cancer

Purpose: Near-infrared photoimmunotherapy (NIR-PIT) is a localized molecular cancer therapy combining a photosensitizer-conjugated mAb and light energy. CD47 is an innate immune checkpoint widely expressed on bladder cancer cells, but absent from luminal normal urothelium. Targeting CD47 for NIR-PIT has the potential to selectively induce cancer cell death and minimize damage to normal urothelium. Experimental Design: The cytotoxic effect of NIR-PIT with anti-CD47-IR700 was investigated in human bladder cancer cell lines and primary human bladder cancer cells derived from fresh surgical samples. Phagocytosis assays were performed to evaluate macrophage activity after NIR-PIT. Anti-CD47-IR700 was administered to murine xenograft tumor models of human bladder cancer for in vivo molecular imaging and NIR-PIT. Results: Cytotoxicity in cell lines and primary bladder cancer cells significantly increased in a light-dose–dependent manner with CD47-targeted NIR-PIT. Phagocytosis of cancer cells significantly increased with NIR-PIT compared with antibody alone (P = 0.0002). In vivo fluorescence intensity of anti-CD47-IR700 in tumors reached a peak 24-hour postinjection and was detectable for at least 14 days. After a single round of CD47-targeted NIR-PIT, treated animals showed significantly slower tumor growth compared with controls (P < 0.0001). Repeated CD47-targeted NIR-PIT treatment further slowed tumor growth (P = 0.0104) and improved survival compared with controls. Conclusions: CD47-targeted NIR-PIT increased direct cancer cell death and phagocytosis resulting in inhibited tumor growth and improved survival in a murine xenograft model of human bladder cancer.
Electrical control of spatial resolution in mixed-dimensional heterostructured photodetectors

Significance Spatial resolution can be electrically switched between high-resolution mode (HRM) and low-resolution mode in mixed-dimensional heterostructured photodetectors, and an interference fringe with 334 nm in period can be discriminated by setting at HRM. This can be attributed to the asymmetric geometry and the gate-tunable Fermi levels of these low-dimensional materials. It reveals great potential of the mixed-dimensional architectures in future nanoelectronics and nano-optoelectronics. Low-dimensional nanomaterials, such as one-dimensional (1D) nanomaterials and layered 2D materials, have exhibited significance for their respective unique electronic and optoelectronic properties. Here we show that a mixed-dimensional heterostructure with building blocks from multiple dimensions will present a synergistic effect on photodetection. A carbon nanotube (CNT)–WSe2–graphene photodetector is representative on this issue. Its spatial resolution can be electrically switched between high-resolution mode (HRM) and low-resolution mode (LRM) revealed by scanning photocurrent microscopy (SPCM). The reconfigurable spatial resolution can be attributed to the asymmetric geometry and the gate-tunable Fermi levels of these low-dimensional materials. Significantly, an interference fringe with 334 nm in period was successfully discriminated by the device working at HRM, confirming the efficient electrical control. Electrical control of spatial resolution in CNT–WSe2–graphene devices reveals the potential of the mixed-dimensional architectures in future nanoelectronics and nano-optoelectronics.
Mosquito Small RNA Responses to West Nile and Insect-Specific Virus Infections in Aedes and Culex Mosquito Cells

Small RNA mediated responses are essential for antiviral defence in mosquitoes, however, they appear to differ per virus-vector combination. To further investigate the diversity of small RNA responses against viruses in mosquitoes, we applied a small RNA deep sequencing approach on five mosquito cell lines: Culex tarsalis CT cells, Aedes albopictus U4.4 and C6/36 cells, Ae. aegypti Aag2 cells (cleared from cell fusing agent virus and Culex Y virus (CYV) by repetitive dsRNA transfections) and Ae. pseudoscutellaris AP-61 cells. De novo assembly of small RNAs revealed the presence of Phasi Charoen-like virus (PCLV), Calbertado virus, Flock House virus and a novel narnavirus in CT cells, CYV in U4.4 cells, and PCLV in Aag2 cells, whereas no insect-specific viruses (ISVs) were detected in C6/36 and AP-61 cells. Next, we investigated the small RNA responses to the identified ISVs and to acute infection with the arthropod-borne West Nile virus (WNV). We demonstrate that AP-61 and C6/36 cells do not produce siRNAs to WNV infection, suggesting that AP-61, like C6/36, are Dicer-2 deficient. CT cells produced a strong siRNA response to the persistent ISVs and acute WNV infection. Interestingly, CT cells also produced viral PIWI-interacting (pi)RNAs to PCLV, but not to WNV or any of the other ISVs. In contrast, in U4.4 and Aag2 cells, WNV siRNAs, and pi-like RNAs without typical ping-pong piRNA signature were observed, while this signature was present in PCLV piRNAs in Aag2 cells. Together, our results demonstrate that mosquito small RNA responses are strongly dependent on both the mosquito cell type and/or the mosquito species and family of the infecting virus.
Saffron (Crocus sativus L.) in Ocular Diseases: A Narrative Review of the Existing Evidence from Clinical Studies

Saffron (Crocus sativus L.) and its main constituents, i.e., crocin and crocetin, are natural carotenoid compounds, which have been reported to possess a wide spectrum of properties and induce pleiotropic anti-inflammatory, anti-oxidative, and neuroprotective effects. An increasing number of experimental, animal, and human studies have investigated the effects and mechanistic pathways of these compounds in order to assess their potential therapeutic use in ocular diseases (e.g., in age related macular degeneration, glaucoma, and diabetic maculopathy). This narrative review presents the key findings of published clinical studies that examined the effects of saffron and/or its constituents in the context of ocular disease, as well as an overview of the proposed underlying mechanisms mediating these effects.
Utility and safety of endobronchial ultrasound‐guided transbronchial needle aspiration and endoscopic ultrasound with an echobronchoscope‐guided fine needle aspiration in children with mediastinal pathology

Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) and endoscopic ultrasound with an echobronchoscope‐guided fine needle aspiration (EUS‐B‐FNA) are useful modalities in the evaluation of mediastinal pathologies in adults. However, sparse data are available in children.
The influence of night-time electronic device use on subsequent sleep and propensity to be physically active the following day

ABSTRACT This study investigated the effect of acute night-time blue-light exposure through electronic device use on sleep quality/quantity, exercise motivation and perceived exertion during exercise the following day. In a randomised, crossover design, 14 participants read a book on an iPad (light) or a hard-copy book (control) one hour before bedtime. Small but not significant differences in perceived sleep quality and quantity and measured sleep efficiency were found between light and control trials, suggesting that sleep may be negatively affected following one night of electronic device use. This did not impact motivation to exercise or perceived exertion during exercise the following day.
A Systematic Review of Data Collection Techniques Used to Measure Preschool Children’s Knowledge of and Preference for Physical Activity

Background: Early childhood has been identified as a crucial period in which children develop physical activity preferences and behaviors. Both the knowledge of and preferences for physical activity are key proximal indicators of activity choices in children. Thus, accurate data collection tools are required to measure these variables. This review evaluates the data collection techniques that have been utilised to assess preschool children’s knowledge of and preference for physical activity, and examines the validity and reliability of existing techniques. Methods: A systematic search for relevant studies published from 1980 through to December 2017 was conducted via ProQuest, CINAHL, Embase, Scopus, ERIC, PubMed, MEDLINE, and ScienceDirect. Results: Fourteen studies were eligible for inclusion in the review. The identified studies employed a limited but disparate range of techniques to assess children’s physical activity knowledge and preferences. Findings reveal that four techniques were consistently used across the reviewed studies, including: interviews, structured play-based activities, questionnaires, and observations. Only four out of 14 included studies reported the assessment of the validity of the data collection tool used, and six reported testing the measures for at least one type of reliability. Conclusion: There is a need for validated and reliable measures to assess children’s knowledge of and preference for physical activity. Greater consideration is required to align data collection techniques with the characteristics, needs and abilities of this study population.