Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding Aging in Place: Home and Community Features, Perceived Age-Friendliness of Community, and Intention Toward Aging in Place.

BACKGROUND AND OBJECTIVES Promoting age-friendliness of communities and supporting aging in place (AIP) are of great importance. Based on processes of belonging and agency, which suggest that person-environment interactions influence residents' evaluations and behaviors related to the environment, this study aims to examine the interrelationship between the availability of age-friendly features, perceived age-friendliness of community, and intention toward AIP. RESEARCH DESIGN AND METHODS This study used the 2015 AARP Age-Friendly Community Survey, which includes 66 home and neighborhood features under the eight domains specified by the WHO's Age-Friendly Cities Guidelines. A series of regression and mediational analyses were conducted to test hypotheses. RESULTS Overall, a greater availability of age-friendly features was positively associated with perceived age-friendliness of community and AIP intention. The relationship between age-friendly features and AIP intention was mediated by perceived age-friendliness of community (50.3% to 96% of the total effects). When perceived age-friendliness of community was introduced to models, the direct effects of housing, outdoor spaces and buildings, and transportation domains remained significant. DISCUSSION AND IMPLICATIONS Findings suggest that a greater availability of age-friendly features influences older adults' perception on their community, leading to the development of a desire to age-in-place, supporting processes of belonging and agency. Domains of housing, outdoor spaces and buildings, and transportation may be the most important features in promoting age-friendliness of community and the key determinants of aging in place. Policy makers and practitioners may need to prioritize promoting age-friendly built environment before social environment in building age-friendly communities.
Vitamin D and anti-Müllerian hormone concentration in human follicular fluid individually aspirated from all patient follicles

Abstract Objective The main aim of this prospective study was to investigate the relationship between intrafollicular vitamin D and anti-Müllerian hormone (AMH) concentration and its impact on oocyte quality and developmental competence. Methods The analysis was performed on 208 follicular fluid (FF) samples obtained from 33 patients undergoing ovarian stimulation as part of in vitro fertilization (IVF) treatment that included intracytoplasmic sperm injection. Results Our study shows that vitamin D concentration in FF varies according to the developmental stage of the oocyte and corelates with embryo development status on day 3, while AMH concentration in FF is not correlated with the developmental potential of an oocyte. We demonstrated that the levels of vitamin D and AMH were higher in FF than in serum. Moreover we showed that AMH and vitamin D levels were positively correlated in FF but not in serum. Conclusion FF-AMH levels do not appear to be a suitable as noninvasive test of the developmental potential of an oocyte, while FF-vitamin D level can be used to evaluate whether embryos obtained from particular oocytes have potential of reaching the third day of culture. However, our results encourage further research to be carried out on a larger number of patients and testing additional components found in FF such as androgens.
Structural basis for the stereospecific inhibition of the dual proline/hydroxyproline catabolic enzyme ALDH4A1 by trans‐4‐hydroxy‐L‐proline

Aldehyde dehydrogenase 4A1 (ALDH4A1) catalyzes the final steps of both proline and hydroxyproline catabolism. It is a dual substrate enzyme that catalyzes the NAD+‐dependent oxidations of L‐glutamate‐γ‐semialdehyde to L‐glutamate (proline metabolism), and 4‐hydroxy‐L‐glutamate‐γ‐semialdehyde to 4‐erythro‐hydroxy‐L‐glutamate (hydroxyproline metabolism). Here we investigated the inhibition of mouse ALDH4A1 by the six stereoisomers of proline and 4‐hydroxyproline using steady‐state kinetics and X‐ray crystallography. Trans‐4‐hydroxy‐L‐proline is the strongest of the inhibitors studied, characterized by a competitive inhibition constant of 0.7 mM, followed by L‐proline (1.9 mM). The other compounds are very weak inhibitors (approximately 10 mM or greater). Insight into the selectivity for L‐stereoisomers was obtained by solving crystal structures of ALDH4A1 complexed with trans‐4‐hydroxy‐L‐proline and trans‐4‐hydroxy‐D‐proline. The structures suggest that the 10‐fold greater preference for the L‐stereoisomer is due to a serine residue that hydrogen bonds to the amine group of trans‐4‐hydroxy‐L‐proline. In contrast, the amine group of the D‐stereoisomer lacks a direct interaction with the enzyme due to a different orientation of the pyrrolidine ring. These results suggest that hydroxyproline catabolism is subject to substrate inhibition by trans‐4‐hydroxy‐L‐proline, analogous to the known inhibition of proline catabolism by L‐proline. Also, drugs targeting the first enzyme of hydroxyproline catabolism, by elevating the level of trans‐4‐hydroxy‐L‐proline, may inadvertently impair proline catabolism by the inhibition of ALDH4A1.
Unresolved Clinical Issues in Thermal Ablation of Benign Thyroid Nodules: Regrowth at Long-Term Follow-Up

Copyright © 2021 The Korean Society of Radiology Laser ablation (LA) for the treatment of symptomatic benign thyroid nodules was first introduced in the early 2000s [1]. In Korea, radiofrequency ablation (RFA) began in 2002, and a large population study was published in 2008 [2]. Other thermal ablation (TA) techniques, such as microwave ablation and high-intensity focused ultrasound, are also used in clinical practice. The Korean Society of Thyroid Radiology (KSThR) published its first thyroid RFA guideline in 2012, which was revised in 2018 [3,4]. These guidelines have greatly contributed to the establishment and spread of TA worldwide. Early experiences with TA showed promising short-term results, with early studies suggesting that the primary purpose of RFA for benign thyroid nodules was debulking to reduce pressure symptoms, rather than complete ablation [5]. However, Huh et al. [6] reported regrowth of nodules from unablated peripheral regions and suggested repeat treatment with a moving-shot technique, which is a safer method of ablating peripheral portions of the nodule. As long-term follow-up results have been released, issues surrounding regrowth and multiple treatments have emerged. Thus, the need for setting new treatment goals has increased [7]. Unresolved Clinical Issues in Thermal Ablation of Benign Thyroid Nodules: Regrowth at Long-Term Follow-Up Jung Suk Sim, Jung Hwan Baek Department of Radiology, Withsim Clinic, Seongnam, Korea; Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
Unravelling cases of clozapine-related Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in patients reported otherwise: A systematic review

Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a drug-induced hypersensitivity reaction. Aims: Aim was to review reports of clozapine-related reactions fulfilling the registry of severe cutaneous adverse reaction (RegiSCAR) criteria for DRESS syndrome reported as such or otherwise, to provide a descriptive overview of demographic patterns, clinical manifestations, and DRESS course and investigate associations between demographic, DRESS parameters, and clinical outcomes. Methods: This review was conducted following preferred reporting items for systematic reviews and meta-analyses guidelines and registered with PROSPERO (registration number CRD42020156385). We searched PubMed/Embase/PsychInfo/Cochrane for reports of clozapine-related reactions meeting RegiSCAR criteria. Associations between RegiSCAR scores and time-to-recovery with demographic/clinical variables were assessed. Demographic/clinical characteristics of patients with versus without reported DRESS were compared using non-parametrical tests. Results: We identified 26 reports of 27 patients meeting RegiSCAR criteria. Males (n = 19, 70.4%) and patients with schizophrenia (n = 18, 66.7%) were mainly affected. Twelve patients (44.4%) received clozapine-monotherapy. DRESS symptoms manifested within a month after clozapine initiation (n = 24, 88.9%). Lungs and liver were the most common organs involved (n = 12, 44.4%; n = 11, 40.7%), with a mean time to recovery of 33.75 days. Clozapine rechallenge led to DRESS recurrence in four patients. Death rate was 7.4%. No associations were detected between RegiSCAR criteria or days to recovery with any demographic/clinical variables. No differences between patients with versus without reported DRESS were detected. Conclusions: Clozapine-related DRESS may be rare, but also underreported. Clinicians need to be aware of it even in patients under clozapine-monotherapy or without skin rash.
First-in-Human, Phase 1 Dose-Escalation Study of Biparatopic Anti-HER2 Antibody–Drug Conjugate MEDI4276 in Patients with HER2-positive Advanced Breast or Gastric Cancer

MEDI4276 is a biparatopic tetravalent antibody targeting two nonoverlapping epitopes in subdomains 2 and 4 of the HER2 ecto-domain, with site-specific conjugation to a tubulysin-based microtubule inhibitor payload. MEDI4276 demonstrates enhanced cellular internalization and cytolysis of HER2-positive tumor cells in vitro. This was a first-in-human, dose-escalation clinical trial in patients with HER2-positive advanced or metastatic breast cancer or gastric cancer. MEDI4276 doses escalated from 0.05 to 0.9 mg/kg (60- to 90-minute intravenous infusion every 3 weeks). Primary endpoints were safety and tolerability; secondary endpoints included antitumor activity (objective response, progression-free survival, and overall survival), pharmacokinetics, and immunogenicity. Forty-seven patients (median age 59 years; median of seven prior treatment regimens) were treated. The maximum tolerated dose was exceeded at 0.9 mg/kg with two patients experiencing dose-limiting toxicities (DLTs) of grade 3 liver function test (LFT) increases, one of whom also had grade 3 diarrhea, which resolved. Two additional patients reported DLTs of grade 3 LFT increases at lower doses (0.4 and 0.6 mg/kg). The most common (all grade) drug-related adverse events (AEs) were nausea (59.6%), fatigue (44.7%), aspartate aminotransferase (AST) increased (42.6%), and vomiting (38.3%). The most common grade 3/4 drug-related AE was AST increased (21.3%). Five patients had drug-related AEs leading to treatment discontinuation. In the as-treated population, there was one complete response (0.5 mg/kg; breast cancer), and two partial responses (0.6 and 0.75 mg/kg; breast cancer)—all had prior trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1). MEDI4276 has demonstrable clinical activity but displays intolerable toxicity at doses >0.3 mg/kg.
Leptospirosis with pulmonary haemorrhage and multiple organ failure: a case report and literature review

Pulmonary haemorrhage is an important complication of leptospirosis. We herein report an uncommon case of severe pulmonary haemorrhage and multiple organ failure caused by leptospirosis in a 49-year-old man who was previously healthy. He was a farm worker who was admitted to the hospital because of haemoptysis. He had worked in a paddy field 4 days prior to admission. Chest computed tomography revealed pulmonary haemorrhage, which rapidly deteriorated into haemorrhagic shock and multiple organ failure. Based on the patient’s possible history of contact with contaminated water and the DNA sequence of Leptospira detected in his bronchoalveolar lavage fluid, the patient was diagnosed with pulmonary haemorrhagic leptospirosis. Despite the administration of a fluid bolus, norepinephrine, broad-spectrum antibiotics, and haemostatics, and even with administration of a blood transfusion and extracorporeal life support, the pulmonary haemorrhage could not be controlled effectively. The patient eventually died of haemorrhagic shock. Leptospirosis can be a life-threatening disease despite aggressive treatment, even with extracorporeal life support. Next-generation sequencing can provide important diagnostic clues for patients with atypical leptospirotic symptoms.
Moderators of the Liking Bias in Judgments of Moral Character

Previous research found evidence for a liking bias in moral character judgments because judgments of liked people are higher than those of disliked or neutral ones. This article sought conditions moderating this effect. In Study 1 (N = 792), the impact of the liking bias on moral character judgments was strongly attenuated when participants were educated that attitudes bias moral judgments. In Study 2 (N = 376), the influence of liking on moral character attributions was eliminated when participants were accountable for the justification of their moral judgments. Overall, these results suggest that although liking biases moral character attributions, this bias might be reduced or eliminated when deeper information processing is required to generate judgments of others’ moral character.
Elevated B-type natriuretic peptide (BNP) and soluble thrombomodulin (sTM) indicates severity and poor prognosis of sepsis.

BACKGROUND To study the predictive value of B-type natriuretic peptide (BNP) and soluble thrombomodulin (sTM) in the severity stratification and prognosis evaluation of sepsis. METHODS The clinical data of 137 sepsis patients diagnosed and treated in Sichuan Provincial People's Hospital from May 2018 to November 2020 were retrospectively analyzed. Meanwhile, 121 healthy individuals were selected as the control group. Patients with sepsis were allocated into the mild group, severe group, and shock group according to the severity. According to the 28-day prognosis, the patients were allocated into the death group and survival group. The plasma BNP and serum sTM levels in different groups were compared, and their prognostic value was evaluated. RESULTS Patients with sepsis had significantly higher levels of BNP and sTM than the healthy control group (P<0.05). The levels of BNP and sTM in the mild group were significantly lower than those in the severe group and shock group, and both BNP and sTM were positively correlated with Acute Physiology and Chronic Health Status (APACHE) II score (r=0.595, 0.516, P<0.05). The levels of BNP and sTM in the death group were significantly higher than those in the survival group (P<0.05). The area under curve (AUC) of BNP combined with sTM was significantly greater than that of BNP or sTM alone for the prognosis of sepsis (P<0.05). When the cut-off value of BNP was 625.68 pg/mL, the sensitivity and specificity were 77.42% and 89.42%, respectively. When the cut-off value of sTM was 10.53 ng/mL, the sensitivity and specificity were 83.87% and 94.34%, respectively. CONCLUSIONS Patients with sepsis have significantly higher serum BNP and sTM levels which are positively correlated with the severity of the disease. Both of the 2 indexes have good prognostic value, and the predictive value is higher when combined.
Repercussions of covid-19-related national lockdown on emergency surgery department: a longitudinal cohort monocentric study.

BACKGROUND COVID-19 lockdown restrictions in conjunction with the pervasive hospital fear endured by the vast majority of the population played a fundamental role in discouraging access to emergency departments (EDs). We aimed at investigating whether and how the COVID-19 outbreak limited access to ED and affected urgent surgical activities during and immediately after the 2-month pandemic-related national lockdown. METHODS Data regarding patients who accessed to the surgical ED were retrospectively collected. Analysed time-periods included: 'Pre-COVID-19 Era', 'COVID-19 Era' considered as the period of full national lockdown and 'Post-COVID-19 Era' after easing of lockdown measures. Consecutive emergency surgical procedures and ED admissions before, during and after COVID-19-lockdown were retrieved and analysed. RESULTS There was a significant decrease in overall ED admissions and in all-specialty surgical consultations (P<0.01) throughout the outbreak. Once national lockdown was eased, we recorded a subsequent rebound 5-fold rise of emergency surgical procedures compared to COVID-19 group (P=0.011). Time-to-surgery was significantly greater in 'COVID-19 era' and 'post-COVID-19 era' compared to 'pre-COVID-19' group (22.56±4.78, 75.99±15.89 and 16.73 ±1.76 hours, respectively) (P<0.01). A raised incidence of postoperative complications emerged in the 'COVID-19 era' group (37.5%) compared to pre and post-COVID groups (9.1% and 12.5%, respectively; P<0.001). Mortality rate in the 'COVID-19 era' was 31.3% and 7.5% in 'post-COVID-19' group (<0.0001). CONCLUSIONS This study demonstrates the major reduction of emergency surgical procedures and overall ED admissions caused by COVID-19 pandemic. The raised rate of postoperative complications and mortality might be likely due to the superior severity of surgical conditions observed in the 'COVID-19 era' subjects together with a probable deferred pursuit of medical attention.
Hierarchical genetic structure in an evolving species complex: Insights from genome wide ddRAD data in Sebastes mentella

The diverse biology and ecology of marine organisms may lead to complex patterns of intraspecific diversity for both neutral and adaptive genetic variation. Sebastes mentella displays a particular life-history as livebearers, for which existence of multiple ecotypes has been suspected to complicate the genetic population structure of the species. Double digest restriction-site associated DNA was used to investigate genetic population structure in S. mentella and to scan for evidence of selection. In total, 42,288 SNPs were detected in 277 fish, and 1,943 neutral and 97 tentatively adaptive loci were selected following stringent filtration. Unprecedented levels of genetic differentiation were found among the previously defined ‘shallow pelagic’, ‘deep pelagic’ and ‘demersal slope’ ecotypes, with overall mean FST = 0.05 and 0.24 in neutral and outlier SNPs, respectively. Bayesian computation estimated a concurrent and historical divergence among these three ecotypes and evidence of local adaptation was found in the S. mentella genome. Overall, these findings imply that the depth-defined habitat divergence of S. mentella has led to reproductive isolation and possibly adaptive radiation among these ecotypes. Additional sub-structuring was detected within the ‘shallow’ and ‘deep’ pelagic ecotypes. Population assignment of individual fish showed more than 94% agreement between results based on SNP and previously generated microsatellite data, but the SNP data provided a lower estimate of hybridization among the ecotypes than that by microsatellite data. We identified a SNP panel with only 21 loci to discriminate populations in mixed samples based on a machine-learning algorithm. This first SNP based investigation clarifies the population structure of S. mentella, and provides novel and high-resolution genomic tools for future investigations. The insights and tools provided here can readily be incorporated into the management of S. mentella and serve as a template for other exploited marine species exhibiting similar complex life history traits.
Oncolytic Vaccinia Virus Gene Modification and Cytokine Expression Effects on Tumor Infection, Immune Response, and Killing

Oncolytic vaccinia viruses have promising efficacy and safety profiles in cancer therapy. Although antitumor activity can be increased by manipulating viral genes, the relative efficacy of individual modifications has been difficult to assess without side-by-side comparisons. This study sought to compare the initial antitumor activity after intravenous administration of five vaccinia virus variants of the same Western Reserve backbone and thymidine kinase gene deletion in RIP-Tag2 transgenic mice with spontaneous pancreatic neuroendocrine tumors. Tumors had focal regions of infection at 5 days after all viruses. Natural killer (NK) cells were restricted to these sites of infection, but CD8+ T cells and tumor cell apoptosis were widespread and varied among the viruses. Antitumor activity of virus VV-A34, bearing amino acid substitution A34K151E to increase viral spreading, and virus VV-IL2v, expressing a mouse IL2 variant (mIL2v) with attenuated IL2 receptor alpha subunit binding, was similar to control virus VV-GFP. However, antitumor activity was significantly greater after virus VV-A34/IL2v, which expressed mIL2v together with A34K151E mutation and viral B18R gene deletion, and virus VV-GMCSF that expressed mouse GM-CSF. Both viruses greatly increased expression of CD8 antigens Cd8a/Cd8b1 and cytotoxicity genes granzyme A, granzyme B, Fas ligand, and perforin-1 in tumors. VV-A34/IL2v led to higher serum IL2 and greater tumor expression of death receptor ligand TRAIL, but VV-GMCSF led to higher serum GM-CSF, greater expression of leukocyte chemokines and adhesion molecules, and more neutrophil recruitment. Together, the results show that antitumor activity is similarly increased by viral expression of GM-CSF or IL2v combined with additional genetic modifications.
External Quantum Efficiency Improvement with Luminescent Downshifting Layers: Experimental and Modelling

Core-shell quantum dots CdSe/ZnS and lumogen yellow organic dye are characterized by their inclusion in luminescent downshifting (LDS) layers. Layers were deposited on top of crystalline silicon cell (c-Si), dye synthesized solar cell (DSSC), and cadmium telluride (CdTe) minimodules. External quantum efficiency measurements for the solar cell/LDS devices are discussed. Experimental results were compared with an optical model developed by Rothemund, 2014.
Prehospital End-Tidal CO2: A Superior Marker for Mortality Risk in the Acutely Injured Patient

Background Emergency medical personnel must expeditiously triage acutely injured patients to the appropriate medical facility. Efficient and objective variables to facilitate this process and provide information to the receiving trauma center are needed. Currently, multiple variables are used to prognosticate injury severity and risk of mortality including vital signs, mental status, lactate, and base excess. We investigated the prehospital use of end-tidal carbon dioxide (ETCO2) as a noninvasive physiologic measure that can be obtained in the acutely injured patient. Methods We performed a retrospective analysis of 557 acutely injured patients over 2 years at a Level 1 trauma center. All patients arriving as trauma activations with ETCO2 measurements were included in analysis. End-tidal carbon dioxide measurements were categorized as low, normal, and high based on reference levels. Mortality was the primary outcome. Secondary receiver operator curves (ROC) for base excess, venous lactate, blood pressure, and venous pH were compared. We hypothesized ETCO2 levels would be able to predict mortality. Results End-tidal carbon dioxide levels conferred a mortality rate of 38%, 17.3%, and 2.9% for low, normal, and high, respectively (P < .001). Receiver operator curve analysis produced an area under the curve predictive value for ETCO2 (.748) which was superior to lactate (.660), SBP (.578), pH (.560), and base excess (.497). Discussion End-tidal carbon dioxide is a more sensitive and specific predictor of mortality in the acutely injured patient compared to venous lactate, base deficit, blood pressure, or venous pH. Additional studies are needed to determine if ETCO2 can be used as an effective prehospital adjunct to prevent mortality in acutely injured patients.