Slim and robust eye tracker on eyeglass temples with NIR patterned mirrors.

Eye trackers play a crucial role in the development of future display systems, such as head-mounted displays and augmented reality glasses. However, ensuring robustness and accuracy in gaze estimation poses challenges, particularly with limited space available for the transmitter and receiver components within these devices. To address the issues, we propose what we believe is a novel eye tracker design mounted on foldable temples, which not only supports accurate gaze estimation but also provides slim form-factor and unobstructed vision. Our temple-mounted eye tracker utilizes a near-infrared imaging system and incorporates a patterned near-infrared mirror for calibration markers. We present wearable prototypes of the eye tracker and introduce a unique calibration and gaze extraction algorithm by considering the mirror's spatial reflectance distribution. The accuracy of gaze extraction is evaluated through tests involving multiple users with realistic scenarios. We conclude with an evaluation of the results and a comprehensive discussion on the applicability of the temple-mounted eye tracker.

Amplification Failure by the Cepheid Xpert Xpress SARS-CoV-2 Assay due to a Single-Nucleotide Variant of the N Gene in the Omicron Variant.

BACKGROUND: Rapid identification of SARS-CoV-2 infection using molecular testing has played an important role in preventing the spread of COVID-19. However, the failure of SARS-CoV-2 N gene amplification in the Cepheid Xpert SARS-CoV-2 assay could lead to the failed detection of infections, possibly leading to spread. In this study, we examined N gene amplification failure due to a single-nucleotide variant (SNV) in the N2 region of the gene. METHODS: Xpert assay results obtained at our hospital since March 2021 were retrospectively reviewed and samples with strong E gene and failed N gene amplification were selected. Whole-genome sequencing was performed using the Illumina platform. Lineage analyses were conducted and the N2 target region of the US CDC 2019-nCoV real-time PCR primer sequence, used in PCR assays of SARS-CoV-2 infection, was compared with the reference SARS-COV-2 sequence (Wuhan-Hu-1, NC_045512.2). RESULTS: The two samples eligible for this study were classified as BA.5.2 (22B, Omicron) and included two synony-mous SNVs, C29197T and C29200T, respectively. Both variants resulted in synonymous mutation of the N gene encoding alanine. The distribution of variants varied across different countries. CONCLUSIONS: Clinical laboratories performing molecular tests targeting the N gene of SARS-CoV-2 should consider the probability of N gene amplification failure when reporting the test results.

Genetic Diagnosis of Children With Neurodevelopmental Disorders Using Whole Genome Sequencing.

BACKGROUND: Neurodevelopmental disorders (NDDs) have diverse phenotypes. Their genetic diagnoses are often challenged by difficulties of targeting causative genes due to heterogeneous genetic etiologies. The objective of this study was to perform genetic diagnosis of children with NDDs using whole genome sequencing. METHODS: This study included 78 pediatric patients with NDDs and their 152 family members for whole genome sequencing (WGS). All cases except one were families with at least two members. Seventy-five patients had previously undergone other genetic tests besides WGS. Detected variants were classified according to the guidelines of the American College of Medical Genetics and Genomics. RESULTS: Among 78 probands, 26 patients were genetically diagnosed with NDDs through WGS, showing a diagnostic rate of 33.3%. Of them, 22 cases had de novo variants (DNVs) identified through trio analysis. Of these DNVs, half were novel variants. Three structural variants, including a multiexon deletion, a contiguous gene deletion involving 13 Mb, and a retrotransposon insertion, were revealed by WGS. All cases except one had defects in different genes, consistent with the phenotypically diverse nature of NDDs. In addition, three patients were inconclusive, two of them had one likely pathogenic variant in a gene associated with autosomal recessive disease and the other one had no clinical phenotypes associated with the detected DNV. CONCLUSIONS: Our experience demonstrates the advantage of WGS in the diagnosis of NDDs, including detection of copy number variations and also the advantage of trio sequencing for interpretation of DNVs.

Whole-genome sequencing in clinically diagnosed Charcot-Marie-Tooth disease undiagnosed by whole-exome sequencing.

Whole-genome sequencing is the most comprehensive form of next-generation sequencing method. We aimed to assess the additional diagnostic yield of whole-genome sequencing in patients with clinically diagnosed Charcot-Marie-Tooth disease when compared with whole-exome sequencing, which has not been reported in the literature. Whole-genome sequencing was performed on 72 families whose genetic cause of clinically diagnosed Charcot-Marie-Tooth disease was not revealed after the whole-exome sequencing and 17p12 duplication screening. Among the included families, 14 (19.4%) acquired genetic diagnoses that were compatible with their phenotypes. The most common factor that led to the additional diagnosis in the whole-genome sequencing was genotype-driven analysis (four families, 4/14), in which a wider range of genes, not limited to peripheral neuropathy-related genes, were analysed. Another four families acquired diagnosis due to the inherent advantage of whole-genome sequencing such as better coverage than the whole-exome sequencing (two families, 2/14), structural variants (one family, 1/14) and non-coding variants (one family, 1/14). In conclusion, an evident gain in diagnostic yield was obtained from whole-genome sequencing of the whole-exome sequencing-negative cases. A wide range of genes, not limited to inherited peripheral neuropathy-related genes, should be targeted during whole-genome sequencing.

Practical delta check limits for tumour markers in different clinical settings.

OBJECTIVES: Few studies have reported on delta checks for tumour markers, even though these markers are often evaluated serially. Therefore, this study aimed to establish a practical delta check limit in different clinical settings for five tumour markers: alpha-fetoprotein, cancer antigen 19-9, cancer antigen 125, carcinoembryonic antigen, and prostate-specific antigen. METHODS: Pairs of patients' results (current and previous) for five tumour markers between 2020 and 2021 were retrospectively collected from three university hospitals. The data were classified into three subgroups, namely: health check-up recipient (subgroup H), outpatient (subgroup O), and inpatient (subgroup I) clinics. The check limits of delta percent change (DPC), absolute DPC (absDPC), and reference change value (RCV) for each test were determined using the development set (the first 18 months, n=179,929) and then validated and simulated by applying the validation set (the last 6 months, n=66,332). RESULTS: The check limits of DPC and absDPC for most tests varied significantly among the subgroups. Likewise, the proportions of samples requiring further evaluation, calculated by excluding samples with both current and previous results within the reference intervals, were 0.2-2.9% (lower limit of DPC), 0.2-2.7% (upper limit of DPC), 0.3-5.6% (absDPC), and 0.8-35.3% (RCV99.9%). Furthermore, high negative predictive values >0.99 were observed in all subgroups in the in silico simulation. CONCLUSIONS: Using real-world data, we found that DPC was the most appropriate delta-check method for tumour markers. Moreover, Delta-check limits for tumour markers should be applied based on clinical settings.

A 20-year trend of prevalence and susceptibility to trimethoprim/sulfamethoxazole of Stenotrophomonas maltophilia in a single secondary care hospital in Korea.

Stenotrophomonas maltophilia is a Gram-negative opportunistic pathogen that can cause serious infection. We aimed to analyze the prevalence and susceptibility rates to trimethoprim/sulfamethoxazole of S. maltophilia. We conducted a retrospective study of S. maltophilia isolates from a university hospital from 2001 to 2020. Clinical information, the numbers of isolates and susceptibility rates were analyzed by year. Susceptibility rates and changes in respiratory and non-respiratory samples were compared. 1805 S. maltophilia isolates were identified, of which 81.4% (1469/1805) were from respiratory samples. There was a male predominance and 52% of the isolates were from general wards. The average susceptibility rate was 87.7% and there was no significant annual trend (P = .519). The susceptibility rate was 88.7% in respiratory samples and 84.1% in non-respiratory samples (P = .018). Susceptibility analyses using clinical data over long periods can guide the choice of antimicrobials especially for pathogen whose treatment options are limited.

Enrichment of titin-truncating variants in exon 327 in dilated cardiomyopathy and its relevance to reduced nonsense-mediated mRNA decay efficiency.

Titin truncating variants (TTNtvs) are the most common genetic cause of dilated cardiomyopathy (DCM). Among four regions of titin, A-band enrichment of DCM-causing TTNtvs is widely accepted but the underlying mechanism is still unknown. Meanwhile, few reports have identified exon 327 as a highly mutated A-band exon but the degree of exon 327 enrichment has not been quantitatively investigated. To find the real hotspot of DCM-causing TTNtvs, we aimed to reassess the degree of TTNtv enrichment in known titin regions and in exon 327, separately. In addition, we tried to explain exon 327 clustering in terms of nonsense-mediated mRNA decay (NMD) efficiency and a dominant negative mechanism recently proposed. Research papers focusing on TTNtvs found in patients with DCM were collected. A total of 612 patients with TTNtv-realated DCM were obtained from 10 studies. In the four regions of TTN and exon 327, the degree of TTNtvs enrichment was calculated in a way that the effect of distribution of highly expressed exons was normalized. As a result, exon 327 was the only region that showed significant enrichment for DCM-related TTNtv (p < .001). On the other hand, other A-band exons had almost the same number of TTNtv of random distribution. A review of RNAseq data revealed that the median allelic imbalance deviation of exon 327 TTNtvs was .04, indicating almost zero NMD. From these findings, we propose that the widely accepted A-band enrichment of DCM-related TTNtv is mostly attributable to exon 327 enrichment. In addition, based on the recently demonstrated dominant negative mechanism, the extremely low NMD efficiency seems to contribute to exon 327 enrichment.

A Preterm Infant with Feeding Aspiration Diagnosed with BOR Syndrome, Confirmed Case by Whole-Genome Sequencing and Structural Variant Calling.

Branchiootorenal (BOR) syndrome is a rare autosomal dominant inherited disease with a prevalence of approximately 1 in 40,000 newborns. This disease is characterized by hearing loss, preauricular pits, branchial fistulas or cysts, and renal dysplasia. We discovered a case of BOR syndrome in a premature 2-week-old female infant with a gestational age of 32 weeks and two days. She and her family had major symptoms and a family history of BOR. BOR syndrome was confirmed by whole-genome sequencing and structural variant calling, which revealed an EYA1 exon 5-6 deletion. The infant had recurrent sleep and feeding cyanosis with second branchial anomalies. Via videofluoroscopic swallowing study and a modified barium swallow test, penetration into the vocal cords was observed before and during swallowing when bottle feeding. This is the first report of a preterm infant early diagnosed with BOR syndrome in which deletion margin was accurately identified by whole-genome sequencing and structural variant calling in Republic of Korea.

Adsorption, Wetting, Growth, and Thermal Stability of the Protic Ionic Liquid Diethylmethylammonium Trifluoromethanesulfonate on Ag(111) and Au(111).

We have studied the adsorption, wetting, growth, and thermal evolution of the protic IL diethylmethylammonium trifluoromethanesulfonate ([dema][TfO]) on Au(111) and Ag(111). Ultrathin films were deposited at room temperature (RT) and at 90 K, and were characterized in situ by angle-resolved X-ray photoelectron spectroscopy. For both surfaces, we observe that independent of temperature, initially, a closed 2D wetting layer forms. While the film thickness does not increase past this wetting layer at RT, at 200 K and below, "moderate" 3D island growth occurs on top of the wetting layer. Upon heating, on Au(111), the [dema][TfO] multilayers desorb at 292 K, leaving an intact [dema][TfO] wetting layer, which desorbs intact at 348 K. The behavior on Ag(111) is much more complex. Upon heating [dema][TfO] deposited at 90 K, the [dema]+ cations deprotonate in two steps at 185 and 305 K, yielding H[TfO] and volatile [dema]0. At 355 K, the formed H[TfO] wetting layer partly desorbs (∼50%) and partly decomposes to form an F-containing surface species, which is stable up to 570 K.

Enrichment effects of ionic liquid mixtures at polarized electrode interfaces monitored by potential screening.

The behavior of ionic liquids (ILs) at charged interfaces is pivotal for their application in supercapacitors and electrochemical cells. Recently, we demonstrated for neat ILs that potential screening at polarized electrode interfaces shows a characteristic voltage dependence, as determined in situ by X-ray photoelectron spectroscopy. Herein, we use this fingerprint-type behavior to characterize the nature of the IL/electrode interfaces for IL mixtures of [C8C1Im][Tf2N] and [C8C1Im]Cl on Au and Pt electrodes. For Au, the IL/electrode interfaces are dominated by the Cl- anions, even down to a 0.1 mol% [C8C1Im]Cl content. In contrast, [Tf2N]- anions enrich at the IL/Pt electrode interfaces down to 10 mol% [C8C1Im][Tf2N]; only at lower concentrations does a transition to Cl- enrichment occur. These mixture studies demonstrate that even small concentrations of another IL or contamination, e.g. remaining from synthesis, can strongly influence the situation at charged IL interfaces.

Recent Progress in the Manipulation of Molecules with DC Electric Fields.

The structure and reactivity of a molecule in the condensed phase are governed by its intermolecular interactions with the surrounding environment. The multipole expansion of each molecule in the condensed phase indicates that the intermolecular interactions are essentially electrostatic (e.g., ion-dipole, dipole-dipole, dipole-quadrupole, dipole-induced dipole). The electrostatic field is a fundamental language of intermolecular communications. Therefore, understanding the influence of the electrostatic field on a molecule, that is, the mechanisms by which an electrostatic field manipulates a molecule, from the perspective of molecular structure, energy states, and dynamics is indispensable for illustrating and, by extension, controlling the chemistry in molecular systems.In this Account, we describe the recent progress made in manipulation of molecular processes using an external DC electrostatic field. An electrostatic field with unprecedentedly high strength (≤4 × 108 V/m) was applied in a controlled manner across a molecular film sample using the ice film nanocapacitor method. This field strength is comparable in magnitude to that of weak intermolecular interactions such as van der Waals interactions in the condensed phases. The samples were prepared using a thin film growing technique in vacuum to obtain the desired chemically tailored molecular systems. The examples of prepared systems included small molecules and molecular clusters isolated in cryogenic Ar matrices, frozen molecular films in amorphous or crystalline phase, and interfaces of multilayered molecular films. The response of the molecules to the external field was monitored by reflection-absorption infrared spectroscopy. This approach allowed us to investigate a variety of molecular systems with various intermolecular strength and environments under the influence of strong electrostatic fields. The range of observed molecular behaviors includes the manipulation of molecular orientation, intramolecular dynamics, and proton transfer reactions as an example of stereodynamic control of chemical reactivity. These observations improve our understanding of molecular behaviors in strong electric fields and broaden our perspective on electrostatic manipulation of molecules. This information is also relevant to a variety of research topics in physical and biological sciences where electric fields play a role in molecular and biological functions.

A Sensitive and Specific Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Quantification of Salivary Melatonin and Cortisol: Development and Comparison With Immunoassays.

Melatonin and cortisol are clinically important for diagnosing sleep and mood disorders. We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous measurement of salivary melatonin and cortisol concentrations according to the Clinical and Laboratory Standards Institute guidelines. Additionally, we compared the LC-MS/MS assay with immunoassays, ELISA (Direct Salivary Melatonin Elisa EK-DSM, Bühlmann Laboratories AG, Schönenbuch, Switzerland) and electrochemiluminescence immunoassay (Cortisol II, Roche, Mannheim, Germany), using 121 saliva samples. The LC-MS/MS assay exhibited good performance in terms of linearity, precision, accuracy, limit of detection, lower limit of quantification, extraction recovery, carry-over, and matrix effect. The LC-MS/MS assay and immunoassays showed strong correlation (Pearson's r=0.910 for melatonin, r=0.955 for cortisol), but demonstrated a significant mean bias of 23.2% (range 54.0-143.7%) for melatonin and 48.9% (range 59.7-184.7%) for cortisol. Our LC-MS/MS assay provided more sensitive and reliable salivary melatonin and cortisol quantification results compared with immunoassays.

Comparison of Three Blood Collection Tubes for 35 Biochemical Analytes: The Becton Dickinson Barricor Tube, Serum Separating Tube, and Plasma Separating Tube.

The Barricor tube (Becton Dickinson [BD], Sunnyvale, CA, USA) was recently developed to mechanically separate plasma by increasing the centrifugation rate. We compared the Barricor tube with existing serum- and plasma-based tubes based on 35 biochemical analytes and preanalytical turnaround time (TAT). Blood samples were collected from 30 healthy volunteers in a Barricor tube, serum separating tube (SST, Vacutainer SST II Tube 8.5 mL, #368972; BD), or plasma separating tube (PST, Vacutainer PST Tube 8.0 mL, #367964; BD) in random order. Next, 27 chemistry analytes, six immunochemistry analytes, and two cardiac markers were compared using Passing-Bablok regression and the Bland-Altman method. Preanalytical TAT was measured for each tube. The Barricor tube exhibited bias exceeding the desirable limit for nine and four analytes compared with the SST and PST, respectively. The Barricor tube lactate dehydrogenase value showed a bias of -10.29% and -9.86% compared with that of the SST and PST, respectively. The preanalytical TAT of Barricor tube was 8.8 minutes, which was the shortest among the three tubes. The clinical performance of the Barricor tube was equivalent to that of the SST and PST for most analytes, with an apparent advantage in preanalytical TAT. When using the Barricor tube, the reference range needs to be changed for some analytes that exceed the desirable bias limit.

Electric Field Effect on Condensed-Phase Molecular Systems. X. Interconversion Dynamics and Vibrational Stark Effect of Hydrogen Chloride Clusters in an Argon Matrix.

In this study, the effect of a strong (≤4 × 108 V·m-1) dc electric field on hydrogen chloride (HCl) dimers and trimers isolated in a solid argon matrix has been investigated using the ice film nanocapacitor and reflection-absorption infrared spectroscopy methods. The H-Cl vibrational bands of the HCl dimers showed a linear Stark frequency shift and an increased intensity under the applied electric field, and these changes were reversible with the electric field strength. This behavior indicated that the dimers were reoriented by the applied electric field. The reorientation occurred via tunneling inversion of individual HCl subunits of the dimer, which interconverted the proton-accepting and -donating HCl subunits, as observed for the heterodimers HCl-DCl and DCl-HCl. The interconversion of dimers could occur even at low electric field strength (∼107 V·m-1) and was almost complete above the field strength of 1.0 × 108 V·m-1. In contrast, the asymmetric H-Cl stretching bands of the HCl trimers exhibited Stark broadening under the influence of the electric field without a shift in frequency or change in intensity. This behavior indicated that the cyclic structure of the HCl trimer was stable even when subjected to a strong electric field. The Stark sensitivity factor (Δµ) of H-Cl vibrations was deduced from the Stark effect analysis of the HCl dimer and trimer bands, which gave the following: ΔµD1 = 2.3 ± 0.2 cm-1/(108 V·m-1) for the proton-acceptor subunit of the dimer, ΔµD2 = 5.1 ± 0.5 cm-1/(108 V·m-1) for the proton-donor subunit of the dimer, and ΔµT = 4.5 ± 0.5 cm-1/(108 V·m-1) for the asymmetric stretching vibration of the cyclic trimer.

Temperature-Dependent Surface Enrichment Effects in Binary Mixtures of Fluorinated and Non-Fluorinated Ionic Liquids.

Using angle-resolved X-ray photoelectron spectroscopy (ARXPS), we investigate the topmost nanometers of various binary ionic liquid (IL) mixtures at different temperatures in the liquid state. The mixtures consist of ILs with the same [PF6 ]- anion but two different cations, namely 3-methyl-1-(3,3,4,4,4-pentafluorobutyl)imidazolium hexafluorophosphate, [PFBMIm][PF6 ], and 1-butyl-3-methylimidazolium hexafluorophosphate, [C4 C1 Im][PF6 ], with 10, 25, 50 and 75 mol % content of [PFBMIm][PF6 ]. We observe a preferential enrichment of the fluorinated chain in the topmost layer, relative to the bulk composition, which is most pronounced for the lowest content of [PFBMIm][PF6 ]. Upon cooling the mixtures stepwise from 95 °C until surface charging effects in XPS indicate solidification, we observe a pronounced increase in surface enrichment of the fluorinated chain with decreasing temperature in the liquid state. In contrast to the mixtures with lower [PFBMIm][PF6 ] contents, cooling the 75 mol % mixture additionally shows an abrupt decrease of the fluorinated chain signal before complete solidification occurs, which is assigned to partial precipitation effects.

Diagnostic Performance of the GENEDIA MTB/NTM Detection Kit for Detecting Mycobacterium tuberculosis and Nontuberculous Mycobacteria With Sputum Specimens.

The GENEDIA MTB/NTM Detection Kit (GENEDIA MTB/NTM; Green Cross Medical Science Corp., Chungbuk, Korea) is a multiplex real-time PCR assay used for differential identification of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM). While the importance of differential identification of MTB/NTM is recognized, there is limited data on the performance of GENEDIA MTB/NTM assay to date. A total of 687 consecutive sputum specimens were cultured and analyzed with the GENEDIA MTB/NTM and GENEDIA MTB assays. Nineteen specimens (2.8%) were MTBC-positive, and 69 (10.0%) were NTM-positive based on mycobacterial culture. All specimens showed concordant results for MTBC using both assays, with a kappa value of 1.00, overall sensitivity of 63.2% (12/19), and specificity of 100% (668/668). The overall NTM sensitivity and specificity were 23.2% (16/69) and 99.7% (616/618) for GENEDIA MTB/NTM. The association between NTM-positivity using GENEDIA MTB/NTM and the diagnosis of NTM pulmonary disease was not statistically significant. In conclusion, the two real-time PCR assays showed similar diagnostic performance for MTBC detection. However, the sensitivity for NTM detection was lower than that for MTBC detection.

Potential Screening at Electrode/Ionic Liquid Interfaces from In Situ X-ray Photoelectron Spectroscopy.

A new approach to investigate potential screening at the interface of ionic liquids (ILs) and charged electrodes in a two-electrode electrochemical cell by in situ X-ray photoelectron spectroscopy has been introduced. Using identical electrodes, we deduce the potential screening at the working and the counter electrodes as a function of applied voltage from the potential change of the bulk IL, as derived from corresponding core level binding energy shifts for different IL/electrode combinations. For imidazolium-based ILs and Pt electrodes, we find a significantly larger potential screening at the anode than at the cathode, which we attribute to strong attractive interactions between the imidazolium cation and Pt. In the absence of specific ion/electrode interactions, asymmetric potential screening only occurs for ILs with different cation and anion sizes as demonstrated for an imidazolium chloride IL and Au electrodes, which we assign to the different thicknesses of the electrical double layers. Our results imply that potential screening in ILs is mainly established by a single layer of counterions at the electrode.

Few layer 2D pnictogens catalyze the alkylation of soft nucleophiles with esters.

Group 15 elements in zero oxidation state (P, As, Sb and Bi), also called pnictogens, are rarely used in catalysis due to the difficulties associated in preparing well-structured and stable materials. Here, we report on the synthesis of highly exfoliated, few layer 2D phosphorene and antimonene in zero oxidation state, suspended in an ionic liquid, with the native atoms ready to interact with external reagents while avoiding aerobic or aqueous decomposition pathways, and on their use as efficient catalysts for the alkylation of nucleophiles with esters. The few layer pnictogen material circumvents the extremely harsh reaction conditions associated to previous superacid-catalyzed alkylations, by enabling an alternative mechanism on surface, protected from the water and air by the ionic liquid. These 2D catalysts allow the alkylation of a variety of acid-sensitive organic molecules and giving synthetic relevancy to the use of simple esters as alkylating agents.

Entropy-Driven Spontaneous Reaction in Cryogenic Ice: Dissociation of Fluoroacetic Acids.

Chemical reactions are extremely difficult to occur in ice at low temperature, where atoms and molecules are frozen in position with minimal thermal energy and entropy. Contrary to this general behavior, certain weak acids including fluoroacetic acids dissociate spontaneously and more efficiently in cryogenic ice than in aqueous solution at room temperaure. The enhanced reactivity of weak acids is an unexpected consequence of proton-transfer equilibrium in ice. The configurational entropy of protons in ice shifts the acid dissociation equilibrium forward. This configurational entropy, although a solid-state property, is comparatively large in magnitude with the entropy of vaporization and can effectively drive proton-transfer reactions in ice.