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Hung-Chang Liao,1,2 Cheng-Yi Huang,3,4 Ya-huei Wang5,6 1Department of Health Policy and Management, Chung Shan Medical University, Taichung, Taiwan; 2Department of Medical Management, Chung Shan Medical University Hospital, Taichung, Taiwan; 3School of Nursing, Chung Shan Medical University, Taichung, Taiwan; 4Department of Nursing, Chung Shan Medical University Hospital, Taichung, Taiwan; 5Department of Applied Foreign Languages, Chung Shan Medical University, Taichung, Taiwan; 6Department of Medical Education, Chung Shan Medical University Hospital, Taichung, TaiwanCorrespondence: Ya-huei WangDepartment of Applied Foreign Languages, Chung Shan Medical University, Taichung, TaiwanEmail yhuei@csmu.edu.twObjective: This study aimed to develop an appropriate scale accessing healthcare students’ and providers’ humanistic professional awareness (HPAS-HSP).Methods: Following a literature review, stakeholder interviews, and panel discussions for item generation, 65 items for the HPAS-HSP scale were created based on a nine-point Likert scale, with 9 indicating “strongly agree” and 1 indicating “strongly disagree.” A pilot study using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), with seven hundred twenty-five medical care students and providers in Taiwan as the total sample number of the study, was administered to examine the practicability of the HPAS-HSP scale. The statistics software SPSS and AMOS 24.0 were used to examine the psychometric properties of the scale, including internal consistency, convergent validities, discriminant validities, and exploratory and confirmatory factor analysis.Results: The EFA resulted in 21 items in three factors, with 66.221% of the total variance explained: “personal integrity and accountability” (9 items; 51.763% of the variance explained), “sensitivity to others” (6 items; 8.667% of the variance explained), and “medical professional competence” (6 items; 5.791% of the variance explained). The Cronbach’s alphas for the three subscales and the entire questionnaire ranged from 0.892 to 0.949. The CFA results yielded 20 items, with the same three factors, and demonstrated good model fit in the χ2/df ratio (1.130; p = 0.140), CFI (0.998), TFI (0.998), and RMSEA (0.013). The composite alphas ranged between 0.900 and 0.969. Convergent and discriminant validity also confirmed the stability and consistency of the scale.Conclusion: The statistical results demonstrated that the HPAS-HSP scale can be a measure to assess healthcare students’ and providers’ humanistic professional awareness.Keywords: humanistic professional awareness, healthcare students and providers, scale development, psychometric properties

A 14-year 10-month-old female requested full mouth rehabilitation with protrusive lips and hopelessly decayed maxillary left first molar and mandibular right first molar. The advantages and disadvantages of various possible treatment alternatives were thoroughly discussed. The dilemma between asymmetrical orthodontic space closure and the implant-supported prosthesis was solved by the application of autotransplantation. The treatment progressed well and resulted in satisfactory occlusion and profile.

Acceptance sampling, the most widely used technique in practice, provides rules for making decisions on product acceptance with specified quality standards. A quick-switching sampling (QSS) system,...

Purpose Cholesterol in lipoprotein(a) [Lp(a)-C] is commonly estimated as 30% of the measured Lp(a) mass. However, difficulties in the accurate measurement of Lp(a) mass, along with the inaccuracy of the 30% assumption, produce erroneous values when LDL-C is corrected for Lp(a) [LDL-CLp(a)corr]. Our aim was to develop a new formula for LDL-CLp(a)corr to reduce this error. Methods We developed a new formula to calculate Lp(a)-C from the molar measurement of Lp(a), which is Lp(a) nmol/L × 0.077 = Lp(a)-C mg/dL. The calculated Lp(a)-C is subtracted from LDL-C to obtain LDL-CLp(a)corr. The results obtained with our novel formula versus the conventional formula were compared in 440 samples from 239 participants enrolled in the BANTING study. Results With the conventional formula, approximately 7% of samples with low LDL-C resulted in negative LDL-CLp(a)corr values. With the new formula, no negative LDL-CLp(a)corr values occurred. Among groups with the highest Lp(a)/apoB ratio (p p Lp(a)corr was significantly underestimated by the conventional formula, which may result in the undertreatment of some patients. Conclusion The new formula provides more reliable estimates of LDL-CLp(a)corr than the conventional formula. Trial registration: ClinicalTrials.gov NCT02739984.

BACKGROUND Lipoprotein(a) is a presumed risk factor for atherosclerotic cardiovascular disease. Olpasiran is a small interfering RNA that reduces lipoprotein(a) synthesis in the liver. METHODS We conducted a randomized, double-blind, placebo-controlled, dose-finding trial involving patients with established atherosclerotic cardiovascular disease and a lipoprotein(a) concentration of more than 150 nmol per liter. Patients were randomly assigned to receive one of four doses of olpasiran (10 mg every 12 weeks, 75 mg every 12 weeks, 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo, administered subcutaneously. The primary end point was the percent change in the lipoprotein(a) concentration from baseline to week 36 (reported as the placebo-adjusted mean percent change). Safety was also assessed. RESULTS Among the 281 enrolled patients, the median concentration of lipoprotein(a) at baseline was 260.3 nmol per liter, and the median concentration of low-density lipoprotein cholesterol was 67.5 mg per deciliter. At baseline, 88% of the patients were taking statin therapy, 52% were taking ezetimibe, and 23% were taking a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor. At 36 weeks, the lipoprotein(a) concentration had increased by a mean of 3.6% in the placebo group, whereas olpasiran therapy had significantly and substantially reduced the lipoprotein(a) concentration in a dose-dependent manner, resulting in placebo-adjusted mean percent changes of -70.5% with the 10-mg dose, -97.4% with the 75-mg dose, -101.1% with the 225-mg dose administered every 12 weeks, and -100.5% with the 225-mg dose administered every 24 weeks (P

Tigecycline has in vitro bacteriostatic activity against a broad spectrum of bacteria, including carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the role of tigecycline in treatment of nosocomial pneumonia caused by CR-GNB remains controversial and clinical evidences are limited. We aimed to investigate the clinical benefits of tigecycline as part of the combination treatment of nosocomial CR-GNB pneumonia in intensive care unit (ICU).This multi-centre cohort study retrospectively enrolled ICU-admitted patients with nosocomial pneumonia caused by CR-GNB. Patients were categorized based on whether add-on tigecycline was used in combination with at least one anti-CR-GNB antibiotic. Clinical outcomes and all-cause mortality between patients with and without tigecycline were compared in the original and propensity score (PS)-matched cohorts. A subgroup analysis was also performed to explore the differences of clinical efficacies of add-on tigecycline treatment when combined with various anti-CR-GNB agents.We analysed 395 patients with CR-GNB nosocomial pneumonia, of whom 148 received tigecycline and 247 did not. More than 80% of the enrolled patients were infected by CR-Acinetobacter baumannii (CRAB). A trend of lower all-cause mortality on day 28 was noted in tigecycline group in the original cohort (27.7% vs. 36.0%, p = 0.088). In PS-matched cohort (102 patient pairs), patients with tigecycline had significantly lower clinical failure (46.1% vs. 62.7%, p = 0.017) and mortality rates (28.4% vs. 52.9%, p 0.001) on day 28. In multivariate analysis, tigecycline treatment was a protective factor against clinical failure (PS-matched cohort: aOR 0.52, 95% CI 0.28-0.95) and all-cause mortality (original cohort: aHR 0.69, 95% CI 0.47-0.99; PS-matched cohort: aHR 0.47, 95% CI 0.30-0.74) at 28 days. Kaplan-Meier survival analysis in subgroups of patients suggested significant clinical benefits of tigecycline when added to a colistin-included (log rank p value 0.005) and carbapenem-included (log rank p value 0.007) combination regimen.In this retrospective observational study that included ICU-admitted patients with nosocomial pneumonia caused by tigecycline-susceptible CR-GNB, mostly CRAB, tigecycline as part of a combination treatment regimen was associated with lower clinical failure and all-cause mortality rates.

This study investigates an AR (autoregressive)-filtered version of several conventional diagnostic tests for cross-sectional dependence in large mixed panels when both N and T are large, including ...

Polymerase chain reaction (PCR)-based diagnostic testing is the gold standard method for pathogen identification (ID) with recent developments enabling automated PCR tests for point-of-care (POC) use. However, multiplexed identification of several pathogens in PCR assays typically requires optics for an equivalent number of fluorescence channels, increasing instrumentation's complexity and cost. In this study, we first developed ratiometric PCR that surpassed one target per color barrier to allow multiplexed identification while minimizing optical components for affordable POC use. We realized it by amplifying pathogenic targets with fluorescently labeled hydrolysis probes with a specific ratio of red-to-green fluorophores for each bacterial species. We then coupled ratiometric PCR and automated magnetic beads-based sample preparation within a thermoplastic cartridge and a portable droplet magnetofluidic platform. We named the integrated workflow POC-ratioPCR. We demonstrated that the POC-ratioPCR could detect one out of six bacterial targets related to urinary tract infections (UTIs) in a single reaction using only two-color channels. We further evaluated POC-ratioPCR using mock bacterial urine samples spiked with good agreement. The POC-ratioPCR presents a simple and effective method for enabling broad-based POC PCR identification of pathogens directly from crude biosamples with low optical instrumentation complexity.

An important goal for the producers is to stimulate the purchase intention of consumers so that the profit can be increased. An attractive warranty policy can not only represent the quality of prod...

A 28-GHz high linearity active up-conversion mixer using 28-nm CMOS is presented in this letter. To enhance the modulated output power level under high-order modulation with IM3 improvement in the high IF input power region, the second-order intermodulation (IM2) signal injection technique is adopted. The positive third-order intermodulation (IM3) signal is generated by mixing the IM2 signal and IF input signal with transistors in the transconductance stage biasing in triode region. Therefore, by combining these opposite IM3 signal at the output of transconductance stage, the IM3 distortion can be alleviated. Besides, the proposed mixer achieves an IM3 distortion improvement in a wide IF power range. The measurement results demonstrate conversion gain (CG) of −6.4 dB and output 1-dB compression point (OP1 dB) of −2.2 dBm with 19 mW. The two-tone measurement results exhibit 10.2 dBm output third-order intercept point (OIP3). Furthermore, with the modulation measured results using single-carrier 256-QAM signal, the proposed mixer also exhibits a distinguished output power enhancement when the linearizer turns on. To the best of the author’s knowledge, this design is the first demonstration and implemented of an IM2 signal injection technique in millimeter-wave frequency, which also improves the output power level of the high-order modulation measurement.

A fully integrated one-stage cascode wideband power amplifier (PA) in 65-nm CMOS technology is presented in this letter. A matching technique is leveraged to achieve broadband matching network, which provides optimum load impedance for maximum output power within a wide operating frequency range. The proposed PA shows measured results of 24.5-dBm saturated output power ( $P_{\mathrm {sat}}$ ) covering the full $Ka$ -band (26.5–40 GHz) and 38.2% output 1-dB compression point (OP1dB) fractional bandwidth (BW) from 25 to 37 GHz. To the best of the authors’ knowledge, the proposed PA demonstrates superior output power BW performance compared with the reported state-of-the-art $Ka$ -band CMOS PAs.

We report the results of a study exploring the ability to exploit molecular heterogeneity in DNA methylation for improving the performance of liquid biopsy-based screening for early-stage (I & II) non-small cell lung cancer (NSCLC). Annual low-dose CT (LDCT) screening is currently recommended for adults aged 50 or older who are at high-risk of developing lung cancer. While this approach has resulted in improvements in survival, the false positive rate of lung nodules detection by LDCT remains over 95%, leading to unnecessary invasive follow-up procedures and further points to the need for new, complementary methods to improve diagnostics performance and reduce patient risk. DNA methylation biomarkers have demonstrated considerable potential as tumor-specific biomarkers for blood-based detection of early-stage NSCLC. Nonetheless, cell-free DNA (cfDNA) assessment techniques, such as methylation-specific PCR (MSP) or bisulfite sequencing, have limited sensitivity to assess epigenetic heterogeneity of rare epiallelic variants in a cost-effective manner. Here we reported a new platform, named REM-DREAMing (Ratiometric-Encoded Multiplex Discrimination of Rare EpiAlleles by Melt), which provides a simple, low-cost solution for multiplexed assessment of loci-specific DNA methylation heterogeneity at single molecule sensitivity. The microfluidic nanoarray contains four independent but identical 10,040 nanowell modules. Methylation biomarkers are differentiated by a ratiometric fluorescence scheme and the assessment of individual epiallele species of each locus are achieved through digitization in the nanoarray and precise high-resolution melt (HRM) analysis. In this study, we explore the potential utility of REM-DREAMing as a complementary assay for improving LDCT screening of NSCLC by testing a cohort of 48 clinical samples (28 cancer and 20 control samples) of low-volume liquid biopsy specimens from patients with CT-scan indeterminant pulmonary nodules. A machine learning algorithm incorporating logistic regression models with leave-one-out cross validation was developed to identify a proper methylation density threshold of each biomarker in the panel. Evaluation of the receiver operation characteristic (ROC) curve yielded an area under the curve (AUC) of 0.97 (95% CI, 0.94-1) with 93% sensitivity at 95% specificity for the REM-DREAMing assay, compared with 93% sensitivity at 62% specificity achieved using a traditional, MSP-based approach. These results suggest that the assessment of intermolecular epigenetic heterogeneity can provide superior clinical performance for cfDNA methylation and noninvasive detection of early-stage NSCLC, in particular. Our results warrant further investigation in a larger sample cohort to validate its utility for improving routine screening of NSCLC in high-risk populations. Citation Format: Yang Zhao, Christine M. O’Keefe, James G. Herman, Thomas R. Pisanic, Tza-Huei Wang. REM-DREAMing: Low-cost digital microfluidic analysis of DNA methylation heterogeneity for enhanced, liquid biopsy-based detection of early-stage lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6510.

A variable gain distributed amplifier (VGDA) for the Rx path of ultrawideband phased-array system is implemented in 90-nm CMOS process and presented in this letter. In order to achieve high gain and wideband with relative low dc power dissipation ( $P_{\mathrm {dc}}$ ), the combination of the conventional distributed amplifier (CDA) and the cascaded single-stage distributed amplifier (CSSDA) is utilized to the circuit. Moreover, the active variable termination resistor (AVTR) is adopted to adjust the flatness of gain. According to the experimental results, the proposed VGDA achieves a 21-dB peak gain with a 40-GHz 3-dB bandwidth (3.7–43.7 GHz), 18-dB gain control range (GCR), and 16° maximum phase variation.

Polymerase chain reaction (PCR) is by far the most commonly used method of nucleic acid amplification and has likewise been employed for a plethora of diagnostic purposes. Nonetheless, multiplexed PCR-based detection schemes have hitherto been largely limited by technical challenges associated with nonspecific interactions and other limitations inherent to traditional fluorescence-based assays. Here, we describe a novel strategy for multiplexed PCR-based analysis called Ligation-eNabled fluorescence-Coding PCR (LiNC PCR) that exponentially enhances the multiplexing capability of standard fluorescence-based PCR assays. The technique relies upon a simple, preliminary ligation reaction in which target DNA sequences are converted to PCR template molecules with distinct endpoint fluorescence signatures. Universal TaqMan probes are used to create target-specific multicolor fluorescence signals that can be readily decoded to identify amplified targets of interest. We demonstrate the LiNC PCR technique by implementing a two-color-based assay for detection of 10 ovarian cancer epigenetic biomarkers at analytical sensitivities as low as 60 template molecules with no detectable target cross-talk. Overall, LiNC PCR provides a simple and inexpensive method for achieving high-dimensional multiplexing that can be implemented in manifold molecular diagnostic applications.

This article presents the 38-GHz phased array 32-element Tx and 16-element Rx with 2-GHz IF and 5-GHz LO for fifth-generation (5G) millimeter-wave (MMW) communications. The Tx and Rx beamformers and upconverters/downconverters are fabricated in 65-nm CMOS. The PAs and LNAs near antenna ends are fabricated in 0.15- $\mu \text{m}$ GaAs pHEMT. The eight-element Tx and four-element Rx phased array printed circuit board (PCB) modules integrated with multiple integrated circuits (ICs) and endfire antennas are implemented as unit cells. Four pieces of Tx modules are vertically stacked to construct an $8\times {4}$ brick array (planar array), while four Rx modules are to construct a $4\times {4}$ array. According to 38-GHz over-the-air (OTA) measurements, the 32-element Tx shows 47.5-dBm equivalent isotropic radiated power (EIRP) at OP $_{\mathrm {1 ~dB}}$ with −35.2-dB image rejection ratio (IMRR) and −37.4-dB $\times 8$ LORR. The 16-element Rx at 38 GHz shows −4-dBm OP $_{\mathrm {1~dB}}$ with −28-dB IMRR and −36.6-dB LORR. The Tx and Rx support the beam scanning around ±60° azimuth and ±30° elevation planes. The Tx-to-Rx wireless data link demonstrates 64 quadrature amplitude modulation (QAM)/400 M-BR, 256 QAM/200 M-BR, and 512 QAM/100 M-BR in 20 m. To the best of our knowledge, this work is the first 5G 37-/39-GHz phased array Tx/Rx using the scalable brick array configuration and demonstrating competitive performances compared with previous works.

Quantification of the relative abundance of genetic traits has broad applications for biomarker discovery, diagnostics, and assessing gene expression in biological research. Relative quantification of genes is traditionally done with the 2(−ΔΔCT) method using quantitative real-time polymerase chain reaction (qPCR) data, which is often limited in resolution beyond orders of magnitude difference. The latest techniques for quantification of nucleic acids employ digital PCR or microarrays which involve lengthy sample preparation and complex instrumentation. In this work, we describe a quantitative ratiometric regression PCR (qRR-PCR) method for computing relative abundance of genetic traits in a sample with high resolution from a single duplexed real-time quantitative PCR assay. Instead of comparing the individual cycle threshold (Ct) values as is done for the 2(−ΔΔCT) method, our qRR-PCR algorithm leverages the innate relationship of co-amplified PCR targets to measure their relative quantities using characteristic curves derived from the ratios of normalized qPCR fluorescence curves. We demonstrate the utility of this technique for discriminating the fractional abundance of mixed alleles with resolution below 5%.

In the face of the global threat from drug-resistant superbugs, there remains an unmet need for simple and accessible diagnostic tools that can perform important antibiotic susceptibility testing against pathogenic bacteria and guide antibiotic treatments outside of centralized clinical laboratories. As a potential solution to this important problem, we report herein the development of a microwell array-based resazurin-aided colorimetric antibiotic susceptibility test (marcAST). At the core of marcAST is a ready-to-use microwell array device that is preassembled with custom titers of various antibiotics and splits bacterial samples upon a simple syringe injection step to initiate AST against all antibiotics. We also employ resazurin, which changes from blue to pink in the presence of growing bacteria, to accelerate and enable colorimetric readout in our AST. Even with its simplicity, marcAST can accurately measure the minimum inhibitory concentrations of reference bacterial strains against common antibiotics and categorize the antibiotic susceptibilities of clinically isolated bacteria. With more characterization and refinement, we envision that marcAST can become a potentially useful tool for performing AST without trained personnel, laborious procedures, or bulky instruments, thereby decentralizing this important test for combating drug-resistant superbugs.

This study analyzes how the characters in Lee Unkrich and Adrian Molina’s animated film Coco, mainly Mamá Imelda, Héctor, and Miguel, manage their emotional responses when they are facing loss, bereavement, or other significant changes in their lives. The study uses Elisabeth Kübler-Ross’s five-stage model of grief to analyze how these characters go through the grieving process. Moreover, in order to suggest how those who are grieving can enter into positive states of mind, the study expands on Kübler-Ross’s original model by incorporating a positive mindset of hope. In dialogue with Unkrich and Molina’s film, the study uses Kübler-Ross’s ideas to explore coping mechanisms that can help manage difficult times in life, while also suggesting the benefits of maintaining a positive mindset through hope.

Purpose: The current paradigm in the development of high-grade serous ovarian carcinoma (HGSC) proposes that the majority of HGSCs arise from precursor serous tubal intraepithelial carcinoma (STIC) lesions of the fallopian tube. Here we survey genome-wide methylation in HGSC precursor lesions to identify genomic regions that exhibit high-specificity differential hypermethylation for potential use as biomarkers for detecting STIC and HGSC at stages when curative intervention likely remains feasible. Experimental Design: We first identified quality control criteria for performing reliable methylomic analysis of DNA-limited tubal precursor lesions with the Illumina Infinium MethylationEPIC array. We then used this platform to compare genome-wide methylation among 12 STICs with paired adjacent-normal epithelia, one p53 signature lesion and two samples of concurrent HGSC. The resulting methylomic data were analyzed by unsupervised hierarchical clustering and multidimensional analysis. Regions of high-confidence STIC-specific differential hypermethylation were identified using selective bioinformatic criteria and compared with published MethylationEPIC data from 23 HGSC tumors and 11 healthy fallopian tube mucosae. Results: Unsupervised analysis showed that STICs largely clustered with HGSCs, but were clearly distinct from adjacent-normal fallopian tube epithelia. Forty-two genomic regions exhibited high-confidence STIC-specific differential hypermethylation, of which 17 (40.5%) directly overlapped with HGSC-specific differentially methylated regions. Methylation at these shared loci was able to completely distinguish STIC and HGSC samples from normal and adjacent-normal specimens. Conclusions: Our results suggest that most STICs are epigenetically similar to HGSCs and share regions of differential hypermethylation that warrant further evaluation for potential use as biomarkers for early detection of ovarian HGSC. See related commentary by Ishak and De Carvalho, p. 6083