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Background: The effects of physical activity on the development of different types of cancers have not been comprehensively studied. This nationwide, population-based cohort study investigated the effects of leisure-time physical activity (LTPA) on the development of different types of cancer in Taiwanese adults. A total of 67,890 adult participants (≥ 18 y old) from five rounds (2001, 2005, 2009, 2013, and 2017) of the Taiwan National Health Interview Survey were included. LTPA was measured as the metabolic equivalent of task (MET) expenditure per week and was classified as inactive (< 1 MET-h), low (1-7.49 MET-h), or high (≥ 7.5 MET-h). The LTPA and other covariates were collected through in-person interviews at baseline. New-onset cancer was ascertained from histopathological reports. The Fine-Gray sub-distribution method, with death as a competing risk, was used to determine the impact of LTPA on incident cancer risk., Results: During the 844,337 person-years of follow-up, 4,435 individuals developed cancer. Compared to inactive adults, individuals engaging in high levels of LTPA (≥ 7.5 MET-h/week) were significantly associated with a reduced risk of developing cancer (adjusted hazard ratio [aHR] = 0.93; 95% confidence interval [CI] = 0.87-0.99). However, those with low levels of LTPA (1-7.49 MET-h/week) did not exhibit a significant association with a reduced risk of developing cancer (aHR = 1.00; 95% CI = 0.92-1.10). When considering specific types of cancers, participants with high levels of LTPA (≥ 7.5 MET-h/week) had a significantly lower risk of developing bladder cancer (aHR = 0.68; 95% CI = 0.47-0.99), cervical cancer (aHR = 0.48; 95% CI = 0.24-0.95), and thyroid cancer (aHR = 0.64; 95% CI = 0.44-0.93)., Conclusions: Our findings suggest that high LTPA (≥ 7.5 MET-h/week) is significantly associated with a low risk of incident bladder, cervical, and thyroid cancers., (© 2024. The Author(s).)

Objectives: This cohort study aimed to determine the effect of the COVID-19 pandemic on the prevalence of Metabolic syndrome (MetS) among healthcare workers at a dedicated COVID-19 hospital in Taiwan., Methods: This study recruited 397 healthcare workers who completed health checkups before and during the COVID-19 pandemic. The differences of MetS and its components prevalence before and during the COVID-19 pandemic were compared using the paired samples t-tests for normally distributed variables, and Wilcoxon signed-rank tests for non-normally distributed variables., Results: The prevalence of MetS among healthcare workers significantly increased from 20.9% to 28.7% during the pandemic (p < .001). Central obesity and hypertension were the primary contributors to the development of MetS., Conclusions: COVID-19 pandemic was associated with an increasing prevalence of MetS in healthcare workers, necessitating health-promoting measures to mitigate this risk., Competing Interests: Conflict of Interest for ALL Authors: NONE DECLARED, (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Predictors for coronavirus disease 2019 (COVID-19)-specific and non-COVID-19-specific deaths have not been extensively studied. This cohort study in Taiwan investigated predictors for COVID-19-specific and non-COVID-19-specific deaths among hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. From January to July 2022, 2196 COVID-19 patients at Taipei City Hospital were consecutively recruited in this cohort study. Among the 175 deceased COVID-19 patients, 147 (84.0%) and 28 (16.0%) had COVID-19-specific and non-COVID-19-specific deaths, respectively. After controlling for other covariates, multinomial logistic regressions showed that age ≥ 65 was significantly associated with higher risks for both COVID-19-specific, adjusted odds ratio (AOR) = 6.21; 95% confidence interval (CI) [3.12, 12.35]; and non-COVID-19-specific deaths (AOR = 6.06; 95% CI [1.34, 27.34]). Fully vaccinated individuals (AOR = 0.50; 95% CI [0.33, 0.74]) and Paxlovid recipients (AOR = 0.45; 95% CI [0.20, 0.98]) had lower COVID-19-specific death risks, while comorbid cancer or end-stage renal disease patients faced higher risks of non-COVID-19-specific deaths. Our study findings suggest that vaccination and Paxlovid treatment are crucial for reducing SARS-CoV-2-specific mortalities, while comorbid patients need careful monitoring to reduce non-COVID-19-specific deaths., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Candida is one of the common pathogens in nosocomial infections. Culture is the gold standard for diagnosing candidemia. Candida albicans is identified via the germ tube test, which uses serum as the culture medium, which is costly and time-consuming. This study was conducted to evaluate and compare a relatively simple, fast, and reliable method for the detection of Candida albicans ., Methods: We conducted this randomized case study at Taipei City Hospital (TCH) from January 2023 to August 2023, with a total of 30 specimen culture reports collected and confirmed to be cases of Candida albicans infection. A germ tube test was performed in a 37°C water bath using serum, plasma, and safe plasma products (Fresh Frozen Plasma, FFP). Further, the same procedures were repeated with the addition of 22% bovine serum albumin (BSA) to the identification/culture., Results: By adding BSA, more than 50% of the budding phenomenon was observed in 40 minutes, which shortened the diagnosis time compared with the traditional method (2-3 hours). Using BSA can shorten the identification time for early clinical medication and improve the quality of medical care., Conclusion: Using safer plasma products for germ tube test of candidiasis not only reduced the risk of infection for medical technicians but could also replace the serum used in traditional methods to increase convenience and save time. This study proposed BSA as a germ tube induction medium enhancer, which reduced the culture time, thereby enabling quicker diagnosis of C. albicans infections., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: This cohort study determines the predictors for cause-specific and timing of deaths in patients with COVID-19 in Taiwan., Methods: Patients with laboratory-confirmed COVID-19 admitted to Taipei City Hospital from January 1 to July 31, 2022, were recruited in this cohort. All patients were followed up until death, discharge from the hospital, or August 31, 2022. Early deaths within the first 2 weeks were recorded, and the cause of death was confirmed by the death certificate database of Taiwan. Predictors of cause-specific and timing of deaths of patients with COVID-19 were determined using multinomial Cox proportional hazards regression analysis., Results: Of the 195 (8.0%) patients who died during hospitalization, 147 (84.0%) had COVID-19-specific deaths. Moreover, 54.9% of the deceased patients had early death. After controlling for other covariates, patients aged ≥ 65 years had a higher risk of COVID-19-specific, non-COVID-19-specific, early, and late deaths [adjusted hazards ratio (AHR): 3.85, 6.45, 3.33, and 6.57; 95% confidence interval (CI): 1.91-7.78, 1.17-35.68, 1.51-7.36, and 2.18-19.76, respectively]. Fully vaccinated patients had a lower risk of COVID-19-specific (AHR: 0.68; 95% CI: 0.47-0.98) and early deaths (AHR: 0.54; 95% CI: 0.35-0.84), whereas comorbid patients with chronic obstructive pulmonary disease had a higher risk of non-COVID-19-specific deaths (AHR: 5.43; 95% CI: 1.73-17.03)., Conclusions: This study suggests that prioritizing COVID-19 vaccination and carefully monitoring comorbid patients during hospitalization can reduce the risk of COVID-19-specific and early deaths and non-COVID-19-specific mortalities, respectively., (© 2024. The Author(s).)

Objectives: We perform special-need dental treatment at outpatient department (OPD), under general anesthesia (GA) when necessary, and provide domiciliary dental care. We aim to evaluate the profile and the characteristics of special needs patients (SNPs)., Materials and Methods: We consecutively enrolled 3117 SNPs from January 1, 2019 to December 31, 2022. Eighty patients with rare or genetic diseases were excluded. Demographic data were retrospectively collected., Results: There were totally 3037 SNPs (mean age: 48.2 years; range, 1-100; male-to-female ratio, 1.5); 89.1% (n = 2705) SNPs received dental care at the OPD (OPD-SNPs), 7.9% (n = 239) received dental treatment under GA, and 3.0% (n = 93) received domiciliary dental care. Among those SNPs who received dental treatment under GA (n = 239), 91.2% (n = 218) were mental/intellectual disabled, and most underwent cavity filling (69.5%) and dental extractions (56.5%). OPD-SNPs with mental/intellectual disabilities (n = 1340) received significantly more items of dental treatment than those without (n = 1365). SNPs with more severe disabilities received more fluoride application and ultrasonic scaling (both p < 0.001, trend tests). Interestingly, among OPD-SNPs with mental/intellectual disabilities (n = 1340), more severe patients received more fluoride application (p < 0.001) and ultrasonic scaling (p < 0.001) but fewer root canal treatment (p = 0.007, trend test)., Conclusions: GA benefited SNPs with more dental procedures, including invasive items. SNPs with mental/intellectual disabilities can tolerate more measures and SNPs with more severe mental/intellectual disabilities received more preventive measures but less invasive measures. Similarly, more severe SNPs with other disabilities received more preventive measures but not invasive measures., Clinical Relevance: Our findings may provide useful information for special needs dentists and for doctor-patient communication., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/purpose: Vaccination is the most important preventive measure to protect people from coronavirus disease 2019 (COVID-19). Governments worldwide have prioritized their vaccination policy against COVID-19. However, there is a lack of relevant research on Taiwanese attitudes and considerations toward COVID-19 vaccination. This study aimed to investigate the cognition, preventive behaviors, and attitudes toward COVID-19 vaccines that influence people's willingness to get vaccinated in Taiwan., Methods: From October 1 to 31, 2021, a computer-assisted telephone interview system was used to randomly select Taiwanese people to investigate their COVID-19 preventive behaviors, knowledge, and willingness to be vaccinated., Results: We included 2000 participants of whom 96.45% showed vaccination willingness. The overall mean age and knowledge scores were 48.6 years and 5.78, respectively. All of the participants chose to wear masks, and 80% chose to be vaccinated to prevent COVID-19. Compared with the non-willing vaccination participants, those with younger ages, higher incomes, and higher knowledge scores regarding masks and vaccination were more likely to be vaccinated. Furthermore, apprehensions about vaccine side effects and negative news about COVID-19 vaccines were the major reasons for vaccination hesitancy., Conclusion: To improve people's willingness to get vaccinated, the government should strive to deliver correct knowledge and refute inappropriate negative information about COVID-19 vaccination. Moreover, recommendation by physicians was an important factor for older individuals to decide on receiving the COVID-19 vaccine, and policies could be implemented from this aspect., Competing Interests: Declaration of competing interest All authors report there are no conflicts of interest to declare., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: We recently conducted a phase 2 trial (NCT028865685) evaluating intracranial efficacy of pembrolizumab for brain metastases (BM) of diverse histologies. Our study met its primary efficacy endpoint and illustrates that pembrolizumab exerts promising activity in a select group of patients with BM. Given the importance of aberrant vasculature in mediating immunosuppression, we explored the relationship between immune checkpoint inhibitor (ICI) efficacy and vascular architecture in the hopes of identifying potential mechanisms of intracranial ICI response or resistance for BM., Methods: Using Vessel Architectural Imaging, a histologically validated quantitative metric for in vivo tumor vascular physiology, we analyzed dual-echo DSC/DCE MRI for 44 patients on trial. Tumor and peri-tumor cerebral blood volume/flow, vessel size, arterial and venous dominance, and vascular permeability were measured before and after treatment with pembrolizumab., Results: BM that progressed on ICI were characterized by a highly aberrant vasculature dominated by large-caliber vessels. In contrast, ICI-responsive BM possessed a more structurally balanced vasculature consisting of both small and large vessels, and there was a trend toward a decrease in under-perfused tissue, suggesting a reversal of the negative effects of hypoxia. In the peri-tumor region, the development of smaller blood vessels, consistent with neo-angiogenesis, was associated with tumor growth before radiographic evidence of contrast enhancement on anatomical MRI., Conclusions: This study, one of the largest functional imaging studies for BM, suggests that vascular architecture is linked with ICI efficacy. Studies identifying modulators of vascular architecture, and effects on immune activity, are warranted and may inform future combination treatments., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cerebrovascular dysfunction is a significant contributor to Alzheimer's disease (AD) progression. AD mouse models show altered capillary morphology, density, and diminished blood flow in areas of tau and beta-amyloid accumulation. The purpose of this study was to examine alterations in vascular structure and their contributions to perfusion deficits in the hippocampus in AD and mild cognitive impairment (MCI). Seven individuals with AD and MCI (1 AD/6 MCI), nine cognitively intact older healthy adults, and seven younger healthy adults underwent pseudo-continuous arterial spin labeling (PCASL) and gradient-echo/spin-echo (GESE) dynamic susceptibility contrast (DSC) MRI. Cerebral blood flow (CBF), cerebral blood volume, relative vessel size index (rVSI), and mean vessel density were calculated from model fitting. Lower CBF from PCASL and SE DSC MRI was observed in the hippocampus of AD/MCI group. rVSI in the hippocampus of the AD/MCI group was larger than that of the two healthy groups (FDR- P  = 0.02). No difference in vessel density was detected between the groups. We also explored relationship of tau burden from 18 F-flortaucipir positron emission tomography and vascular measures from MRI. Tau burden was associated with larger vessel size and lower CBF in the hippocampus. We postulate that larger vessel size may be associated with vascular alterations in AD/MCI., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hyperpolarization techniques significantly enhance the sensitivity of magnetic resonance (MR) and thus present fascinating new directions for research and applications with in vivo MR imaging and spectroscopy (MRI/S). Hyperpolarized 13 C MRI/S, in particular, enables real-time non-invasive assessment of metabolic processes and holds great promise for a diverse range of clinical applications spanning fields like oncology, neurology, and cardiology, with a potential for improving early diagnosis of disease, patient stratification, and therapy response assessment. Despite its potential, technical challenges remain for achieving clinical translation. This paper provides an overview of the discussions that took place at the international workshop "New Horizons in Hyperpolarized 13 C MRI," in March 2023 at the Bavarian Academy of Sciences and Humanities, Munich, Germany. The workshop covered new developments, as well as future directions, in topics including polarization techniques (particularly focusing on parahydrogen-based methods), novel probes, considerations related to data acquisition and analysis, and emerging clinical applications in oncology and other fields., (© 2023. The Author(s).)

Aims and Objectives: To assess the prognostic accuracy of the surprise question (SQ) when used by nurses working in hospital wards to determine 1-year mortality in acutely hospitalised older patients., Background: The predictive accuracy of the SQ, when used by general nurses caring for older hospitalised patients, has not been comprehensively studied., Design: A prospective cohort study., Methods: This cohort study recruited consecutive 10,139 older patients (aged ≥65 years) who were admitted to Taipei City Hospital and were evaluated for the needs of palliative care in 2015. All patients were followed up for 12 months or until their death. The c-statistic value was calculated to indicate the predictive accuracy of the SQ and Palliative Care Screening Tool (PCST)., Results: Of all participants, 18.8% and 18.6% had a SQ response of 'no' and a PCST score ≥4, respectively. After controlling for other covariates, an SQ response of 'no' (adjusted hazard ratio [aHR], 2.05; 95% confidence interval [CI], 1.83-2.31) and a PCST score ≥4 (AHR = 1.50; 95% CI: 1.29-1.75) were found to be the independent predictors for patients' 12-month mortality. The C-statistic values of the SQ and the PCST at recognising patients in their last year of life were .663 and .670, respectively. Moreover, there was moderate concordance (k = .44) between the SQ and the PCST in predicting 12-month mortality., Conclusions: SQ response of 'no' and a PCST score ≥4 were independent predictors of 12-month mortality in older patients., Relevance to Clinical Practice: The SQ, when used by nurses working in hospital wards, is effective in identifying older patients nearing the end of life, as well as in providing advance care planning for patients., Patient or Public Contribution: Patients' palliative care needs at admission were assessed by general nurses using the SQ and PCST., (© 2024 John Wiley & Sons Ltd.)

Purpose: We aimed to investigate the effect of altered metabolic syndrome (MetS) status on cancer risk., Methods: From 2002 through 2008 of the Taiwan MJ cohort, there were 111,616 adults who had repeated MetS measurements performed 3.3 years apart and were followed up for cancer incidence over 11.8 years. Cancer was confirmed based on histopathological reports., Results: Participants were categorized as MetS-free (n = 80,409; no MetS at the first or last health screening), MetS-developed (n = 9833; MetS absence at the first screening and presence at the last screening), MetS-recovered (n = 8958; MetS presence at the first screening and absence at the last screening), and MetS-persisted (n = 12,416; MetS presence at the first and last screenings). We used the Fine-Gray sub-distribution method, with death as competing risk, to determine the association between MetS changes and incident cancer risk. During 1320,796 person-years of follow-up, 5862 individuals developed cancer. The incidence rate of cancer per 1000 person-years was 3.89 in the MetS-free, 5.26 in MetS-developed, 4.61 in MetS-recovered, and 7.33 in MetS-persisted groups (P < .001). Compared with the MetS-free group, MetS-persisted individuals had a higher risk of incident cancer., Conclusions: Persistent MetS was found to be associated with a high risk of incident cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: To evaluate oral frailty features present in hospitalized older patients with aspiration pneumonia., Methods: We enrolled hospitalized patients aged ≥50 years and classified them into three groups: the community-acquired, aspiration, and non-community-acquired pneumonia groups. Oral frailty was defined as meeting three or more criteria from the following: choking, and decreased occlusal force, masticatory function, tongue-lip motor function, tongue pressure, and tongue pressure during swallowing., Results: Of 168 patients enrolled, the incidence of aspiration pneumonia was 23.9% (17/71) in patients admitted with pneumonia as the primary diagnosis. The occlusal force and masticatory function were significantly poorer and tongue pressure and tongue pressure during swallowing were significantly lower in the aspiration pneumonia group than in the other two groups. A higher number of chronic comorbidities, poor oral health, and lower tongue pressure during swallowing were significantly associated with aspiration pneumonia. A tongue pressure during swallowing of <10.32 kPa might be a cutoff point for predicting the risk of aspiration pneumonia., Conclusions: Hospitalized patients aged ≥50 years with multiple comorbidities, poor oral hygiene, and oral frailty during swallowing are at a higher risk of developing aspiration pneumonia, especially when their tongue pressure during swallowing is <10.32 kPa. Aspiration pneumonia is a preventable disease. Healthcare professionals should incorporate tongue pressure measurements or other screening tools into routine clinical practice to facilitate the early detection of this condition and intervention. Geriatr Gerontol Int 2024; 24: 351-357., (© 2023 Japan Geriatrics Society.)

The goal of this study was to investigate the origin of brain lactate (Lac) signal in the healthy anesthetized rat after injection of hyperpolarized (HP) [1- 13 C]pyruvate (Pyr). Dynamic two-dimensional spiral chemical shift imaging with flow-sensitizing gradients revealed reduction in both vascular and brain Pyr, while no significant dependence on the level of flow suppression was detected for Lac. These results support the hypothesis that the HP metabolites predominantly reside in different compartments in the brain (i.e., Pyr in the blood and Lac in the parenchyma). Data from high-resolution metabolic imaging of [1- 13 C]Pyr further demonstrated that Lac detected in the brain was not from contributions of vascular signal attributable to partial volume effects. Additionally, metabolite distributions and kinetics measured with dynamic imaging after injection of HP [1- 13 C]Lac were similar to Pyr data when Pyr was used as the substrate. These data do not support the hypothesis that Lac observed in the brain after Pyr injection was generated in other organs and then transported across the blood-brain barrier (BBB). Together, the presented results provide further evidence that even in healthy anesthetized rats, the transport of HP Pyr across the BBB is sufficiently fast to permit detection of its metabolic conversion to Lac within the brain., (© 2023 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Background: The temporality of household income level with overweight/obesity in children has not been extensively studied. Little research has been conducted to determine the impact of household income on the risk of childhood overweight/obesity over time. This population-based cohort study aimed to investigate the impact of household income on the risk of overweight/obesity over time among preschool-aged children in Taiwan., Methods: From 2009 to 2018, we recruited 1,482 preschool-aged children ( ≦ 7 y of age) from low-income households and selected age- and sex-matched controls from non-low-income households for comparison; All participants were selected from those who consistently participated in the Taipei Child Development Screening Program and were monitored for overweight/obesity using body mass index (BMI) until December 31, 2018. Low-income households were defined as those with an average monthly disposable income < 60% of the minimum standard of living expense in Taiwan. The primary outcome was childhood overweight or obesity in study participants, defined as BMI (kg/m 2 ) ≥ 85th percentile or ≥ 95th percentile, respectively. The generalized estimating equations (GEE) model was used to determine the impact of low-income households on the risk of overweight/obesity in study participants., Results: Over 21,450 person-years of follow-up, 1,782 participants developed overweight /obesity, including 452 (30.5%) and 1,330 (22.4%) children from low- and non-low-income households, respectively. The GEE model showed that the first group had a significantly higher risk of becoming overweight/obese than the other during the follow-up period (adjusted odds ratio [aOR] = 1.44, 95% CI: 1.29-1.60). Moreover, children of foreign mothers had a higher risk of becoming overweight/obese than those of Taiwanese mothers during the follow-up period (aOR = 1.51, 95% CI: 1.24-1.8). The subgroup analysis revealed a significant association between low-income households and an increased risk of overweight/obesity in children aged 2-7 years (P =.01). However, this association was not observed in children aged 0-1 years (P >.999)., Conclusions: During the follow-up period, there was a notable correlation between low-income households and an increased risk of preschool-aged children developing overweight or obesity. Implementing health promotion initiatives aimed at reducing overweight and obesity in this demographic is crucial., (© 2024. The Author(s).)

Introduction: Existing evidence evaluating the impact of change in body mass index (BMI) on the risk of all-cause and cardiovascular disease (CVD)-related mortality in older people is limited and inconsistent. This population-based cohort study evaluated the association of changes in BMI over time with all-cause and CVD-related mortality in older adults., Methods: We recruited 55,351 adults aged over 65 years between 2006 and 2011 from Taipei Elderly Health Examination Program who underwent repeated annual health examinations at 3.2-year intervals and were followed up for mortality over 5.5 years. Cox proportional hazard and Fine-Gray sub-distribution hazard models with death from non-CVD causes as the competing risk were used to determine the impact of changes in BMI status on the risk of all-cause or CVD-related mortality, respectively., Results: Over 227,967 person-years of follow-up, 4,054 participants died, including 940 (23.2%) CVD-related deaths. After adjusting for other covariates, &gt;10% decrease in BMI was significantly associated with a higher risk of all-cause (adjusted hazard ratio [AHR] = 1.93; 95% confidence interval [CI]: 1.74-2.13) and CVD-related mortality (AHR = 1.96; 95% CI: 1.60-2.40), compared with stable BMI. Sensitivity analysis showed that a &gt;10% decrease in BMI was significantly associated with a high risk of all-cause and CVD-related mortality in participants with normal weight, underweight, overweight, or obesity at baseline., Conclusion: Older adults with &gt;10% decrease in BMI are at high risk of all-cause and CVD-related mortality. Our findings suggest that older individuals experiencing a substantial reduction in BMI should undergo a thorough evaluation to minimize the risks associated with mortality., (© 2024 S. Karger AG, Basel.)

In light of the growing interest in-vivo deuterium metabolic imaging, hyperpolarized 13 C, 15 N, 3 He, and 129 Xe imaging, as well as 31 P spectroscopy and imaging in large animals on clinical MR scanners, we demonstrate the use of a (radio)frequency converter system to allow X-nuclear MR spectroscopy (MRS) and MR imaging (MRI) on standard clinical MRI scanners without multinuclear capability. This is not only an economical alternative to the multinuclear system (MNS) provided by the scanner vendors, but also overcomes the frequency bandwidth problem of some vendor-provided MNSs that prohibit users from applications with X-nuclei of low magnetogyric ratio, such as deuterium (6.536 MHz/Tesla) and 15 N (-4.316 MHz/Tesla). Here we illustrate the design of the frequency converter system and demonstrate its feasibility for 31 P (17.235 MHz/Tesla), 13 C (10.708 MHz/Tesla), and 15 N MRS and MRI on a clinical MRI scanner without vendor-provided multinuclear hardware., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1- 13 C]pyruvate. Biocompatible formulations of hyperpolarized [1- 13 C]pyruvate in, both, methanol-water mixtures, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected in vivo . Pyruvate-hydrate was also observed as minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe, and scalable molecular imaging., Competing Interests: Notes, Conflict of Interest Disclosures PT, CD, TT and MSR are co-founders and equity holders of Vizma Life Sciences (VLS). CD and PT are employees of VLS. EYC is an equity holder of Vizma Life Sciences. The terms of TT's arrangement have been reviewed and approved by NC State University in accordance with its policy on objectivity in research. EYC and BMG hold ownership stakes in XeUS Technologies Ltd. MSR is a founder and equity holder of Hyperfine Inc. All other authors declare that they have no competing interest.

We report several inductively coupled RF coil designs that are very easy to construct, produce high signal-to-noise ratio (SNR) and high spatial resolution while accommodating life support, anesthesia and monitoring in small animals. Inductively coupled surface coils were designed for hyperpolarized 13 C MR spectroscopic imaging (MRSI) of mouse brain, with emphases on the simplicity of the circuit design, ease of use, whole-brain coverage, and high SNR. The simplest form was a resonant loop designed to crown the mouse head for a snug fit to achieve full coverage of the brain with high sensitivity when inductively coupled to a broadband pick-up coil. Here, we demonstrated the coil's performance in hyperpolarized 13 C MRSI of a normal mouse and a glioblastoma mouse model at 4.7 T. High SNR exceeding 70:1 was obtained in the brain with good spatial resolution (1.53 mm × 1.53 mm). Similar inductively coupled loop for other X-nuclei can be made very easily in a few minutes and achieve high performance, as demonstrated in 31 P spectroscopy. Similar design concept was expanded to splitable, inductively coupled volume coils for high-resolution proton MRI of marmoset at 3T and 9.4T, to easily accommodate head restraint, vital-sign monitoring, and anesthesia delivery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background and Aims: A vegetarian diet is rich in vegetables, fruits, and soy products. Although vegetarian diet is beneficial for improving the health outcomes such as body mass index, metabolic syndrome, cardiovascular disease, and mortality rate, the association between a vegetarian diet and gout incidence is not well known., Methods and Results: We linked the MJ Health Survey Data and MJ Biodata 2000 with the National Health Insurance Research Database (NHIRD) and the National Registration of Death (2000-2018). Information on the diet was collected from the MJ Health Survey Data, and the incidence of gouty arthritis was confirmed using the NHIRD. The Kaplan-Meier survival curve and log-rank test were used to compare the differences between vegetarian and non-vegetarian participants. Cox regression models were used to estimate the risk of the incidence of gouty arthritis. Among 76,972 participants, 37,297 (48.46%) were men, 2488 (3.23%) were vegetarians and the mean age was 41.65 ± 14.13 years. The mean baseline uric acid level was 6.14 ± 1.65 mg/dL. A total of 16,897 participants developed gouty arthritis, including 16,447 (22.08%) non-vegetarians and 450 (18.9%) vegetarians over a mean follow-up of 19 years. Significant differences were observed in the Kaplan-Meier survival curves between vegetarians and non-vegetarians (log-rank p < 0.001). Vegetarians had a significantly decreased incidence of gouty arthritis compared with non-vegetarians (hazard ratio = 0.87, 95% confidence interval = 0.78-0.98, p = 0.02) after adjusting for potential confounders., Conclusion: People with a vegetarian diet had a significantly decreased risk of developing gouty arthritis compared with non-vegetarians in Taiwan., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Older patients tend to have decreased physical functions and more comorbidities than younger patients. At present, the best management for very elderly patients with lung cancer is not known. In this study, we aimed to investigate treatment and mortality risk of older adults with non-small cell cancer (NSCLC) in Taiwan., Methods: This study analyzed data from the Taiwan Cancer Registry database. Patients aged ≥80 years with newly diagnosed NSCLC between 2010 and 2017 were included. Treatment options were categorized as curative, palliative, and no treatment. Patients were followed up until death or December 31, 2020. Univariable and multivariable Cox proportional hazards models were used to estimate mortality risk, and Kaplan-Meier survival curves were drawn., Results: A total of 11 941 patients, aged ≥80 years, with newly diagnosed NSCLC between 2010 and 2017 were identified from the Taiwan Cancer Registry and followed up until 2020. The mean age was 84.4 ± 3.7 years old, and 7468 (62.54%) were men. The Kaplan-Meier survival curves showed significant differences across the three treatment options (log-rank p < 0.001). Results from multivariate Cox regression demonstrated that patients on palliative treatment (adjusted HR: 0.52, 95% CI: 0.48-0.56, p < 0.001) and curative treatment (adjusted HR: 0.45, 95% CI: 0.42-0.48, p < 0.001) had a significantly lower mortality risk than those with no treatment. The subgroup analyses stratified by cancer stages also showed consistent findings., Conclusion: Elderly patients with NSCLC had significantly decreased mortality risk when receiving curative or palliative treatment compared with those without treatment. In the future, further studies are warranted to investigate complications and quality of life of elderly patients with NSCLC during palliative or curative treatment., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

We report dissolution Dynamic Nuclear Polarization (d-DNP) of [ 15 N 3 ]metronidazole ([ 15 N 3 ]MNZ) for the first time. Metronidazole is a clinically approved antibiotic, which can be potentially employed as a hypoxia-sensing molecular probe using 15 N hyperpolarized (HP) nucleus. The DNP process is very efficient for [ 15 N 3 ]MNZ with an exponential build-up constant of 13.8 min using trityl radical. After dissolution and sample transfer to a nearby 4.7 T Magnetic Resonance Imaging scanner, HP [ 15 N 3 ]MNZ lasted remarkably long with T 1 values up to 343 s and 15 N polarizations up to 6.4 %. A time series of HP [ 15 N 3 ]MNZ images was acquired in vitro using a steady state free precession sequence on the 15 NO 2 peak. The signal lasted over 13 min with notably long T 2 of 20.5 s. HP [ 15 N 3 ]MNZ was injected in the tail vein of a healthy rat, and dynamic spectroscopy was performed over the rat brain. The in vivo HP 15 N signals persisted over 70 s, demonstrating an unprecedented opportunity for in vivo studies., (© 2023 Wiley-VCH GmbH.)

Background and Purpose: Although leisure-time physical activity (PA) has established health benefits in older adults, it is equivocal if exercising in environments with high levels of PM 2.5 concentrations is equally beneficial for them. To explore the independent and joint associations of ambient PM 2.5 and PA with all-cause mortality among adults aged 60 or older and to assess the modifying effect of age (60-74 years vs. 75+ years) on the joint associations., Methods: A prospective cohort study based on the MJ Cohort repeat examinations (2005-2016) and the Taiwan Air Quality Monitoring Network and death registry linkages (2005-2022). We included MJ Cohort participants aged 60 or more at baseline who attended the health check-ups at least twice (n = 21,760). Metabolic equivalent hours per week (MET-h/week) of leisure-time PA were computed. Multivariable adjusted associations were examined using time-varying Cox proportional hazard models., Results: There were 3539 all-cause deaths over a mean follow-up of 12.81 (SD = 3.67) years. Ambient PM 2.5 and physical inactivity are both independently associated with all-cause mortality. The joint associations of PA and PM 2.5 concentrations with all-cause mortality differed in the young-old (60-74 years) and the older-old (75+ years) (P for interaction = 0.01); Higher levels of long-term PM 2.5 exposures (≥25 μg/m 3 ) had little influence on the associations between PA and mortality in the young-old (HR = 0.68 (0.56-0.83) and HR = 0.72 (0.59-0.88) for participants with 7.5-<15 and 15+ MET-h/week respectively) but eliminated associations between exposure and outcome in the older-old (HR = 0.91 (0.69-01.21) and HR = 1.02 (0.76-1.38) for participants with 7.5-<15 and 15+ MET-h/week)., Conclusion: Long-term exposures to higher PM 2.5 concentrations may eliminate the beneficial associations of PA with all-cause mortality among adults aged 75 and over., Competing Interests: Declaration of competing interest The authors do not have any conflict of interest to report., (Copyright © 2023. Published by Elsevier Inc.)

T1 relaxation times of the 14 T1 phantom spheres that make up the standard International Society for Magnetic Resonance in Medicine (ISMRM)/National Institute of Standards and Technology (NIST) system phantom are reported at 7 T. T1 values of six of the 14 T1 spheres at 7 T (with T1 > 270 ms) have been reported previously, but, to the best of our knowledge, not all of the T1s of the 14 T1 spheres at 7 T have been reported before. Given the increasing number of 7-T MRI systems in clinical settings and the increasing need for T1 phantoms that cover a wide range of T1 relaxation times to evaluate rapid T1 mapping techniques at 7 T, it is of high interest to obtain accurate T1 values for all the ISMRM/NIST T1 spheres at 7 T. In this work, T1 relaxation time was measured on a 7-T MRI scanner using an inversion-recovery spin-echo pulse sequence and derived by curve fitting to a signal equation that exhibits insensitivity to B 1 + inhomogeneity. Day-to-day reproducibility was within 0.4% and differences between two different RF coils within 1.5%. T1s of a subset of the 14 spheres were also measured by NMR at 7 T for comparison, and the T1 results were consistent between the MRI and NMR measurements. T1 measurements performed at 3 T on the same 14 spheres using the same sequence and fitting method yielded good agreement (mean percentage difference of -0.4%) with the reference T1 values available from the NIST, reflecting the accuracy of the reported technique despite being without the standard phantom housing. We found that the T1 values of all 14 NiCl 2 spheres are consistently lower at 7 T than at 3 T. Although our results were well reproduced, this study represents initial work to quantify the 7-T T1 values of all 14 NIST T1 spheres outside of the standard housing and does not warrant reproducibility of the ISMRM/NIST system phantom as a whole. A future study to assess the T1 values of a version of the ISMRM/NIST system phantom that fits inside typical commercial coils at 7 T will be very helpful. Nonetheless, the details on our acquisition and curve-fitting methods reported here allow the T1 measurements to be reproduced elsewhere. The T1 values of all 14 spheres reported here will be valuable for the development of quantitative MR fingerprinting and rapid T1 mapping for a large variety of research projects, not only in neuroimaging but also in body MRI, musculoskeletal MRI, and gadolinium contrast-enhanced MRI, each of which is concerned with much shortened T1., (© 2022 John Wiley & Sons Ltd.)

Aim: To examine whether changes in metabolic syndrome (MetS) status over time are associated with risk of all-cause and cardiovascular disease related (CVD) mortality., Methods: This prospective cohort study consisted of 544,749 individuals who participated in a self-funded comprehensive health surveillance program offered by Taiwan MJ Health Management Institution between 1998 and 2016. We included 236,216 adults who had at least two repeated MetS measures 5.9 (4.6) years apart and were followed up for mortality over 18.8 (5.2) years. Participants were classified according to the change in their MetS status as follows: MetS-free at both time points (n = 173,116), MetS-developed (n = 22,607), MetS-recovered (n = 13,616), and MetS-persistent (n = 26,877). Multivariable Cox proportional hazards model was used to determine the association between change in MetS status and risk of all-cause and CVD mortality., Results: Over the 4,436,842 person-years follow-up period, 14,226 participants died, including 2671 (19%) of CVD-related causes. The crude CVD mortality rate per 1000 person-years in the study groups were MetS-free, 0.32; MetS-developed, 0.75; MetS-recovered, 1.22; and MetS-persistent, 2.00 (P < 0.001). Compared to the persistent MetS group, participants in the MetS-recovered group had a lower risk of all-cause (adjusted hazard ratio [aHR], 0.87; 95%CI, 0.82-0.92) and CVD mortality (aHR, 0.81; 95% confidence interval [CI], 0.71-0.93). Development of MetS increased the risk for all-cause (aHR, 1.11; 95%CI, 1.05-1.17) and CVD mortality (aHR, 1.22; 95%CI, 1.07-1.39), compared to the MetS-free group., Conclusion: Recovery from MetS was significantly associated with a lower risk of all-cause and CVD mortality, whereas development of MetS was associated with increased risk., Competing Interests: Declaration of Competing Interest We declare no competing interests., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Glucose metabolism is impaired in brain aging and several neurological conditions. Beneficial effects of ketones have been reported in the context of protecting the aging brain, however, their neurophysiological effect is still largely uncharacterized, hurdling their development as a valid therapeutic option. In this report, we investigate the neurochemical effect of the acute administration of a ketone d-beta-hydroxybutyrate (D-βHB) monoester in fasting healthy participants with ultrahigh-field proton magnetic resonance spectroscopy (MRS). In two within-subject metabolic intervention experiments, 7 T MRS data were obtained in fasting healthy participants (1) in the anterior cingulate cortex pre- and post-administration of D-βHB (N = 16), and (2) in the posterior cingulate cortex pre- and post-administration of D-βHB compared to active control glucose (N = 26). Effect of age and blood levels of D-βHB and glucose were used to further explore the effect of D-βHB and glucose on MRS metabolites. Results show that levels of GABA and Glu were significantly reduced in the anterior and posterior cortices after administration of D-βHB. Importantly, the effect was specific to D-βHB and not observed after administration of glucose. The magnitude of the effect on GABA and Glu was significantly predicted by older age and by elevation of blood levels of D-βHB. Together, our results show that administration of ketones acutely impacts main inhibitory and excitatory transmitters in the whole fasting cortex, compared to normal energy substrate glucose. Critically, such effects have an increased magnitude in older age, suggesting an increased sensitivity to ketones with brain aging., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Purpose: New generation of receptor tyrosine kinase inhibitors (RTKIs) have shown to improve survival in many solid tumors. However, an imaging biomarker is needed for patient selection and prediction of treatment response. This study evaluates the use of quantitative changes of HER3 on 68  Ga-NOTA-HER3P1 PET/MRI for prediction of early response to pan-RTKIs in gastric cancer (GCa)., Procedures: GCa cell lines were evaluated for expression of RTKs, and downstream signaling pathways (AKT and MAPK). Cell viability was assessed following 24-72 h of treatment with 0.01-1 µmol/L of afatinib, a pan-RTKI. HER3-expressing afatinib-sensitive (NCI-N87) and resistant cells (SNU16) were selected for evaluation of changes in RTKs expression and downstream pathways, with 24-72 h of 0.1 µmol/L afatinib treatment. 68  Ga-NOTA-HER3P1 PET/MRI was performed in subcutaneous NCI-N87 and SNU16 xenografts (nu:nu, n = 12/group) at baseline and 4 days after afatinib treatment (10 mg/kg, PO, daily). Temporal changes in PET measures were correlated to HER3 expression in tumors, tumor growth rate, and treatment response., Results: With afatinib therapy, NCI-N87 cells showed increased total HER3 expression, and reduction of other RTKs and downstream nodes within 72 h, while SNU16 cells showed no significant change in total HER3 and downstream nodes. 68  Ga-HER3P1 PET/MRI showed increased uptake in NCI-N87 and no significant change in SNU16 tumors (day 4 vs. baseline SUV mean : 3.8 ± 0.7 vs. 1.6 ± 0.6, p < 0.05 in NCI-N87, and 1.5 ± 0.7 vs. 1.7 ± 0.7, p > 0.05 in SNU16). These findings were in concordance with HER3 expression in histopathological analyses and tumor growth over 3 weeks of treatment (mean tumor volume in treated vs. control: 11 ± 17 mm 3 vs. 293 ± 79 mm 3 , p < 0.001 in NCI-N87, and 238 ± 91 mm 3 vs. 282 ± 35 mm 3 , p > 0.05 in SNU16)., Conclusions: Quantitative changes in HER3 PET could be used to predict response to pan-RTKI within few days after initiation of treatment and can help with personalizing GCa management., (© 2022. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Background: The risk of ischemic heart disease (IHD) due to the impact of gonadotropin-releasing hormone (GnRH) agonists among female patients with breast cancer remains a controversy., Methods: Information from the Registry for Catastrophic Illness, the National Health Insurance Research Database (NHIRD), and the Death Registry Database in Taiwan were analyzed. Female patients with breast cancer were selected from the Registry for Catastrophic Illness from January 1, 2000, to December 31, 2018. All the breast cancer patients were followed until new-onset IHD diagnosis, death, or December 31, 2018. A Kaplan-Meier survival curve was drawn to show the difference between patients treated with and without GnRH agonists. The Cox regression analysis was used to investigate the effects of GnRH agonists and the incidence of IHD., Results: A total of 172,850 female patients with breast cancer were recognized with a mean age of 52.6 years. Among them, 6071(3.5%) had received GnRH agonist therapy. Kaplan-Meier survival curves showed a significant difference between patients with and without GnRH therapy (log-rank p < 0.0001). Patients who received GnRH therapy had a significantly decreased risk of developing IHD than those without GnRH therapy (HR = 0.18; 95% CI = 0.14-0.23). After adjusting for age, treatment, and comorbidity, patients who received GnRH therapy still had a significantly lower risk of developing IHD (AHR = 0.5, 95% CI = 0.39-0.64)., Conclusion: The study showed that the use of GnRH agonists for breast cancer treatment was significantly associated with a reduced risk of IHD. Further research is required to investigate the possible protective effect of GnRH on IHD., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

We assessed the microbial and chemical qualities and microbiomes of 14 mustard pickle products coded sequentially from A to N and sold in traditional Taiwanese markets. The results showed that the aerobic plate count and lactic acid bacteria count of commercially available mustard pickle products were 2.18-4.01 and <1.0-3.77 log CFU/g, respectively. Moreover, no coliform bacteria, Escherichia coli , Staphylococcus aureus , Salmonella spp., or Listeria monocytogenes were detected in any of the samples. Analysis of the chemical quality showed that the sulfite content of all samples exceeded 30 ppm, which is the food additive limit in Taiwan. Furthermore, the mean contents of eight biogenic amines in the mustard pickle product samples were below 48.0 mg/kg. The results of high-throughput sequencing showed that the dominant bacterial genera in sample A were Proteus spp. (25%), Vibrio (25%), and Psychrobacter (10%), in sample C they were Weissella (62%) and Lactobacillus (15%), in sample E it was Lactobacillus (97%), and in sample J it was Companilactobacillus (57%). Mustard pickle product samples from different sources contained different microbiomes. The dominant bacterial family was Lactobacillaceae in all samples except for sample A. In contrast, the microbiome of sample A mainly consisted of Morganellaceae and Vibrionaceae , which may have resulted from environmental contamination during storage and sales. The result of this work suggests it may be necessary to monitor sulfite levels and potential sources of bacterial contamination in mustard pickle products, and to take appropriate measures to rule out any public health risks.

This study aimed to assess the use of the high-hydrostatic-pressure (HHP) method (200-600 MPa, 5 min) for bleaching mustard pickle products as an alternative to the conventional method of sulfite addition. The aerobic plate count (APC) and lactic acid bacteria count (LAB) of the samples decreased with the increase in pressure, and the yeast count decreased to no detectable levels. Next, compared with the control group (no high-pressure treatment) the L * (lightness), W (whiteness), Δ E (color difference), and texture (hardness and chewiness) of the HHP-processed samples, which increased significantly with increasing pressure, while the a* (redness) and b* (yellowness) values decreased slightly. This indicates that HHP processing gave the mustard pickle a harder texture and a brighter white color and appearance. Furthermore, when the mustard pickle was treated with HHP 400 and 600 MPa for 5 min and stored at 25 °C for 60 days, it was found that the APC and LAB counts in the HHP-processed group recovered rapidly and did not differ from those in the control group (the non-HHP treated group) but significantly delayed the growth of yeast, the increase in pH value, and total volatile basic nitrogen (TVBN). The high-throughput sequencing (HTS) analysis revealed that the predominant bacterial genera in the non-HHP-treated mustard pickle were Lactiplantibacillus (74%), Lactilactobacillus (12%), and Levilactobacillus (6%); after 60 days of storage, Companilactobacillus (80%) became dominant. However, after 60 days of storage, Lactiplantibacillus (92%) became dominant in the samples processed at 400 MPa, while Levilactobacillus (52%), Pediococcus (17%), and Lactiplantibacillus (17%) became dominant in the samples processed at 600 MPa. This indicated that the HHP treatment changed the lactic acid bacterial flora of the mustard pickle during the storage period. Overall, it is recommended to treat the mustard pickle with HHP above 400 MPa for 5 min to improve its texture and color and delay the deterioration of quality during storage. Therefore, HHP technology has the potential to be developed as a treatment technique to replace the addition of sulfite.

Background/purpose: Latent tuberculosis infection (LTBI) treatment is challenging in long-term care facilities (LTCFs) residents due to the occurrence of medical complexities. However, factors associated with treatment interruption have not been extensively studied. This retrospective cohort study aimed to determine LTBI-associated factors and treatment interruption in LTCF residents and employees in Taiwan., Methods: From May 2017 through September 2020, the residents and employees of 20 LTCFs in Taipei, Taiwan, were screened for LTBI by using QuantiFERON-TB Gold In-Tube test. The LTBI individuals underwent directly observed preventive therapy (DOPT), including regimens of 9-month daily isoniazid (9H) and 3-month weekly isoniazid plus rifapentine (3HP). All the LTBI cases were followed up till treatment completion, death, or treatment interruption., Results: Among 2207 LTCF subjects, 16.8% had LTBI. After controlling for other covariates, residents of public facilities had a significantly higher LTBI prevalence than those of private facilities (adjusted odds ratio [AOR] = 1.43; 95% confidence interval [CI]: 1.08-1.88). Among 264 LTBI cases receiving preventive therapy, 52 (19.7%) had treatment interruption. LTBI cases receiving 3HP were less likely to have treatment interruption than those receiving 9H (AOR = 0.22; 95% CI: 0.07-0.71)., Conclusions: LTCF residents, particular those living in public facilities, had a high LTBI prevalence. 3HP with DOPT is considered the priority regimen for preventive therapy among LTBI cases in LTCFs., Competing Interests: Declaration of competing interest No conflict of interest exists for the author., (Copyright © 2021. Published by Elsevier B.V.)

Background/purpose: Predictors for out-of-hospital cardiac arrest (OHCA) in COVID-19 patients remain unclear. We identified the predictors for OHCA and in-hospital mortality among such patients in community isolation centers., Methods: From May 15 to June 20, 2021, this cohort study recruited 2555 laboratory-confirmed COVID-19 patients admitted to isolation centers in Taiwan. All patients were followed up until death, discharge from the isolation center or hospital, or July 16, 2021. OHCA was defined as cardiac arrest confirmed by the absence of circulation signs and occurring outside the hospital. Multinomial logistic regressions were used to determine factors associated with OHCA and in-hospital mortality., Results: Of the 37 deceased patients, 7 (18.9%) had OHCA and 30 (81.1%) showed in-hospital mortality. The mean (SD) time to OHCA was 6.6 (3.3) days from the symptom onset. After adjusting for demographics and comorbidities, independent predictors for OHCA included age ≥65 years (adjusted odds ratio [AOR]: 13.24, 95% confidence interval [CI]: 1.85-94.82), fever on admission to the isolation center (AOR: 12.53, 95% CI: 1.68-93.34), and hypoxemia (an oxygen saturation level below 95% on room air) (AOR: 26.54, 95% CI: 3.18-221.73). Predictors for in-hospital mortality included age ≥65 years (AOR: 10.28, 95% CI: 2.95-35.90), fever on admission to the isolation centers (AOR: 7.27, 95% CI: 1.90-27.83), and hypoxemia (AOR: 29.87, 95% CI: 10.17-87.76)., Conclusions: Time to OHCA occurrence is rapid in COVID-19 patients. Close monitoring of patients' vital signs and disease severity during isolation is important, particularly for those with older age, fever, and hypoxemia., Competing Interests: Declaration of competing interest No conflict of interest exists for the author., (Copyright © 2022. Published by Elsevier B.V.)

Hepatocellular carcinoma (HCC) surveillance can detect the early stage of tumors and lead to improved survival. Adherence to guideline-concordant HCC surveillance is crucial in at-risk populations, including patients with hepatic C virus (HCV) cirrhosis. This study was conducted to identify patient and provider factors associated with nonadherence to HCC surveillance in patients with HCV cirrhosis. Data were primarily obtained from the Taiwan National Health Insurance Research Database for the 2000 to 2015 period. Adult patients newly diagnosed as having HCV cirrhosis between 2003 and 2012 were enrolled. Each patient was followed up for 3 years and until the end of 2015. Annual HCC surveillance was defined as the uptake of an abdominal ultrasound and alpha-fetoprotein (AFP) test annually during the 3-years follow-up. Nonannual surveillance was defined as the lack of an annual abdominal ultrasound and AFP test during the same 3-years period. Multinomial logistic regression models were applied to determine factors influencing adherence or nonadherence to annual HCC surveillance. We included a total of 4641 patients with HCV cirrhosis for analysis. Of these patients, only 14% adhered to annual HCC surveillance. HCC surveillance improved in later years, compared with the earlier phases of the study period. Patients with HCV cirrhosis comorbid with coronary artery disease (CAD) or chronic obstructive pulmonary disease (COPD) or those with a relatively high number of comorbidities had a significantly higher likelihood of nonadherence. Patients who primarily received care from internists were significantly less likely to exhibit nonadherence to annual HCC surveillance compared with patients receiving care from physicians of other specialties. Patients who primarily received care from physicians practicing in larger hospitals were significantly less likely to exhibit nonadherence. HCC surveillance rates remain unacceptably low among high-risk patients, and our findings may be helpful in the development of effective interventions to increase HCC surveillance. The effective incorporation of HCC surveillance into routine visits for other chronic comorbidities, particularly for CAD or COPD, may be crucial for increasing HCC surveillance., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: Physical activity improves insulin resistance, inhibits inflammation, and decreases the incidence of cardiovascular disease. These are major causes of death in patients with diabetes., Methods: The Taiwan National Health Interview Survey collected baseline characteristics of socioeconomic level, education, marriage, and health behaviour, including leisure time physical activity in 2001, 2005, 2009, and 2013. The National Health Insurance research dataset 2000-2016 contained detailed information on medical conditions, including all comorbidities. All-cause and cardiovascular deaths were confirmed by the National Death Registry., Results: A total of 4859 adults with type 2 diabetes were included in the analysis; 2389 (49 %) were men and the mean±SD age was 60±13 years. Kaplan-Meier curve of all-cause (log-rank P<0.001) and cardiovascular death (log-rank P=0.038) categorized by leisure-time physical activity showed a significant difference. The multivariable Cox regression model showed that those who had more leisure time physical activity had a significantly lower risk of all-cause death than those with no physical activity (physical activity of 1-800 MET-min/week HR = 0.66, 95% CI: 0.54-0.81, physical activity of >800 MET-min/week HR = 0.67, 95% CI: 0.56-0.81). A significant trend was also observed (P <0.001). Similar results were also observed for cardiovascular mortality (physical activity of 1-800 MET-min/week HR = 0.54, 95% CI: 0.36-0.84, physical activity of >800 MET-min/week HR = 0.78, 95% CI: 0.55-1.13)., Conclusion: For those with diabetes, increased leisure-time physical activity significantly reduced risk of all-cause and cardiovascular death. Further research is warranted to determine the proper prescription for physical activity to prolong healthy life., (Copyright © 2022. Published by Elsevier Masson SAS.)

Background: Hospice care involves improving quality of end-of-life (EOL) care and respecting patients' preferences regarding EOL treatment. However, the impact of hospice care services on the utilization of life-sustaining treatments during EOL care in patients with life-limiting diseases has not been extensively studied. Objectives: This nationwide cohort study aimed to determine the impact of hospice care services on the utilization of life-sustaining treatments during the last 3 months of life among people living with HIV/AIDS (PLWHA) in Taiwan. Methods: From 2000 to 2018, we identified adult PLWHA from Taiwan centers for disease control HIV Surveillance System. HIV-infected individuals were defined as positive HIV-1 Western blot. Life-sustaining treatments included cardiopulmonary resuscitation, intubation, mechanical ventilation support, and defibrillation. The association of hospice care services with the utilization of life-sustaining treatments was determined using multiple logistic regression. Results: Of 5691 PLWHA, 2595 (45.9%) subjects utilized life-sustaining treatments during the last 3 months of life. After adjusting for other covariates, PLWHA with hospice care services were less likely to receive life-sustaining treatments during the last 3 months of life than those without the services (adjusted odds ratio [AOR] = .50, 95% confidence interval [CI]: .37-.66). Considering the type of life-sustaining treatments, hospice care services were associated with lower likelihood of receiving cardiopulmonary resuscitation (AOR = .22, 95% CI: .13-.39), endotracheal intubation (AOR = .48, 95% CI: .35-.65), and mechanical ventilation support (AOR = .56, 95% CI: .42-.75). Conclusion: Hospice care services were associated with a lower utilization of life-sustaining treatments during the last 3 months of life among PLWHA.

Purpose: To evaluate the use of hyperpolarized [1- 13 C]pyruvate magnetic resonance spectroscopic imaging (HP- 13 C MRSI) for quantitative measurement of early changes in glycolytic metabolism and its ability to predict response to pan-tyrosine kinase inhibitor (Pan-TKI) therapy in gastric cancer (GCa)., Procedures: Pan-TKI afatinib-sensitive NCI-N87 and resistant SNU16 human GCa cells were assessed for GLUT1, hexokinase-II (HKII), lactate dehydrogenase (LDHA), phosphorylated AKT (pAKT), and phosphorylated MAPK (pMAPK) at 0-72 h of treatment with 0.1 μM afatinib. Subcutaneous NCI-N87 tumor-bearing nude mice underwent [ 18 F]FDG PET/MRI and HP- 13 C MRSI at baseline and 4 days after treatment with afatinib 10 mg/kg/day or vehicle (n = 10/group). Changes in PET and HP- 13 C MRSI metabolic parameters were compared between the two groups. Imaging findings were correlated with tumor growth and histopathology over 3 weeks of treatment., Results: In vitro analysis showed a continuous decrease in LDHA, pAKT, and pMAPK in NCI-N87 compared to SNU16 cells within 72 h of treatment with afatinib, without a significant change in GLUT1 and HKII in either cell type. [ 18 F]FDG PET of NCI-N87 tumors showed no significant change in PET measures at baseline and day 4 of treatment in either treatment group (SUVmean day 4/day 0: 2.7 ± 0.42/2.34 ± 0.38, p = 0.57 in the treated group vs. 1.73 ± 0.66/2.24 ± 0.43, p = 0.4 in the control group). HP- 13 C MRSI demonstrated significantly decreased lactate-to-pyruvate ratio (L/P) in treated tumors (L/P day 4/day 0: 0.83 ± 0.30/1.10 ± 0.20, p = 0.012 vs. 0.94 ± 0.20/0.98 ± 0.30, p = 0.75, in the treated vs. control group, respectively). Response to afatinib was confirmed with decreased tumor size over 3 weeks (11.10 ± 16.50 vs. 293.00 ± 79.30 mm 3 , p < 0.001, treated group vs. control group, respectively) and histopathologic evaluation., Conclusions: HP- 13 C MRSI is a more representative biomarker of early metabolic changes in response to pan-TKI in GCa than [ 18 F]FDG PET and could be used for early prediction of response to targeted therapies., (© 2022. World Molecular Imaging Society.)

White matter lesions (WML) have been linked to cognitive decline in aging as well as in Alzheimer's disease. While hypoperfusion is frequently considered a cause of WMLs due to the resulting reduction in oxygen availability to brain tissue, such reductions could also be caused by impaired oxygen exchange. Here, we tested the hypothesis that venous hyperintense signal (VHS) in arterial spin labeling (ASL) magnetic resonance imaging (MRI) may represent a marker of impaired oxygen extraction in aging older adults. In participants aged 60-80 years (n = 30), we measured cerebral blood flow and VHS with arterial spin labeling, maximum oxygen extraction fraction (OEF max ) with dynamic susceptibility contrast, and WML volume with T 1 -weighted MRI. We found a significant interaction between OEF max and VHS presence on WML volume ( p  = 0.02), where lower OEF max was associated with higher WML volume in participants with VHS, and higher OEF max was associated with higher WML volume in participants without VHS. These results indicate that VHS in perfusion-weighted ASL data may represent a distinct cerebrovascular aging pattern involving oxygen extraction inefficiency as well as hypoperfusion.

Background: New direct-acting antiviral therapies have revolutionized hepatitis C virus (HCV) infection therapy. Nonetheless, once liver cirrhosis is established, the risk of hepatocellular carcinoma (HCC) still exists despite virus eradication. Late HCV diagnosis hinders timely access to HCV treatment. Thus, we determined trends and risk factors associated with late HCV among patients with a diagnosis of HCC in Taiwan., Methods: We conducted a population-based unmatched case-control study. 2008-2018 Claims data were derived from the Taiwan National Health Insurance Research Database. Individuals with an initial occurrence of liver cancer between 2012 and 2018 were included. The late HCV group were referred as individuals who were diagnosed with HCC within 3 years after HCV diagnosis. The control group were referred as individuals who were diagnosed more than 3 years after the index date. We used multivariable logistic models to explore individual- and provider-level risk factors associated with a late HCV diagnosis., Results: A decreasing trend was observed in the prevalence of late HCV-related HCC diagnosis between 2012 and 2018 in Taiwan. On an individual level, male, elderly patients, patients with diabetes mellitus (DM), and patients with alcohol-related disease had significantly higher risks of late HCV-related HCC diagnosis. On a provider level, patients who were mainly cared for by male physicians, internists and family medicine physicians had a significantly lower risk of late diagnosis., Conclusions: Elderly and patients who have DM and alcohol related disease should receive early HCV screening. In addition to comorbidities, physician factors also matter. HCV screening strategies shall take these higher risk patients and physician factors into consideration to avoid missing opportunities for early intervention., (© 2022. The Author(s).)

As one of the highest energy consumer organs in the body, the heart requires tremendous amount of adenosine triphosphate (ATP) to maintain its continuous mechanical work. Fatty acids, glucose, and ketone bodies are the primary fuel source of the heart to generate ATP with perturbations in ATP generation possibly leading to contractile dysfunction. Cardiac metabolic imaging with magnetic resonance imaging (MRI) plays a crucial role in understanding the dynamic metabolic changes occurring in the failing heart, where the cardiac metabolism is deranged. Also, targeting and quantifying metabolic changes in vivo noninvasively is a promising approach to facilitate diagnosis, determine prognosis, and evaluate therapeutic response. Here, we summarize novel MRI techniques used for detailed investigation of cardiac metabolism in heart failure including magnetic resonance spectroscopy (MRS), hyperpolarized MRS, and chemical exchange saturation transfer based on evidence from preclinical and clinical studies and to discuss the potential clinical application in heart failure., Competing Interests: Conflict of interest: Y.Y. is supported by grant from National Institute of Health (1R21JM137227). C.T.N. is supported by grants from National Institute of Health (R01 HL151704, R01 HL159010, R01 HL135242). W.H.W.T. is a consultant for Sequana Medical A.G., Cardiol Therapeutics Inc, and Genomics plc and has received honorarium from Springer Nature for authorship/editorship and American Board of Internal Medicine for exam writing committee participation, all unrelated to the contents of this paper. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. We apologize to all authors whose relevant work could not be cited due to space limitations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background/purpose: This population-based study aimed to compare the accuracy of Rapid antigen detection (RAD) and reverse transcription-polymerase chain reaction (RT-PCR) assays for diagnosing individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the COVID-19 outbreak in Taipei, from May to June 2021., Methods: In response to the outbreak of COVID-19 in mid-May 2021, Taipei City Hospital set up 12 citywide proactive community testing (PCT) stations for early identification of infected individuals from May 17 to June 20, 2021. Individuals with RAD positivity were isolated and later confirmed by RT-PCR. The c-statistic value was estimated to indicate the level of diagnostic accuracy of RAD tests., Results: Of the 33,798 individuals who were evaluated for SARS-CoV-2 infection, 4.4% tested positive for RAD. There was a moderate concordance (kappa = 0.67) between the RAD tests and RT-PCR assay for identifying infectious individuals. The c-statistic value of the RAD test for the diagnosis of SARS-CoV-2 infection was 0.8. There was a positive linear trend between the accuracy of the RAD tests and the prevalence of SARS-CoV-2 infection in the study population (β = 0.04; p = .03). As the cycle threshold value decreased, the sensitivity rate of the RAD tests increased (p < .001). After implementation of the PCT program, the prevalence of COVID-19 decreased from 8.4% to 3.3% (p < .001)., Conclusion: Proactive community testing for SARS-CoV-2 infection using RAD tests could rapidly identify and quarantine the most infectious patients in the early phase of COVID-19 outbreak., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Rice bran and soybean residue are high in nutrients and active ingredients. They are used as media in the solid-state fermentation of Wolfiporia cocos . They not only reduce raw material costs, but also raise the economic value and applications of soybean residues and rice bran. After 30 days of fermentation, the moisture content (w.b.) of the W. cocos product was approximately 40%, requiring it to be pasteurized and dried later. The objective of this research is to use radio frequency (RF) rapid heating technology to pasteurize and dry the solid-state fermented product. A 500 g bag of solid-state fermented W. cocos product took only 30 and 200 s at the RF electrode gap of 15 cm to pasteurize and reduce the moisture content (w.b.) below 15%, respectively; therefore, the methods can be used instead of the traditional 60 min autoclave sterilization and 100 min hot air drying at 45 °C. After RF treatment, the fermented W. cocos product was white, indicating that browning was prevented; the product contained 5.03% mycelium, 9.83% crude polysaccharide, 4.43% crude triterpene, 3.54 mg gallic acid equivalent/g dry weight (DW) of total polyphenols, and 0.38 mg quercetin equivalent/g DW of flavonoid contents and showed a good antioxidant capacity.