bluuebunny/crossref_metadata_2025 huggingface dataset:
Tentative Identification of Etazene (Etodesnitazene) Metabolites in Rat Serum and Urine by Gas Chromatography–Mass Spectrometry and Accurate Mass Liquid Chromatography–Mass Spectrometry
Authors: Grigoryev Andrej , Kavanagh Pierce , Dowling Geraldine , Rodin Igor
Published: January 2022

2-Benzylbenzimidazole derivatives comprise a small but forensically significant group of synthetic opioids. In humans, the metabolism of some members of this group is extensive, with little or none of the parent compound remaining. The recent detection of the 2-benzylbenzimidazole derivative, etazene (etodesnitazene), in products seized in Russia required the detection of its metabolites in biofluids for forensic toxicology purposes. Using gas chromatography--mass spectrometry (GC–MS) and high resolution accurate mass (HRAM) liquid chromatography–mass spectrometry (LC–MS), eight etazene metabolites were found in the urine and serum of rats. These were tentatively identified as products of N-deethylation, O-deethylation, hydroxylation or N-oxidation of benzimidazole moiety and combinations of these processes. The parent substance and its O-deethylated metabolite prevailed in rat serum, while in urine, the level of etazene was low compared to N,O-deethylated and N-deethylated with hydroxylation metabolites. Glucuronidated, sulfonated and glutathionated forms were not found. Taking into account reports on the study of the metabolism of other 2-benzylbenzimidazole derivatives in humans, it may be concluded that the mono-deethylated and mono-hydroxylated metabolites are suitable as target analytes in urine.
Computational investigation of the post-yielding behavior of 3D-printed polymer lattice structures
Authors: Fadeel Abdalsalam , Abdulhadi Hasanain , Newaz Golam , Srinivasan Raghavan , Mian Ahsan
Published: January 2022

Sandwich structures are widely used due to their light weight, high specific strength, and high specific energy absorption. Three-dimensional (3D) printing has recently been explored for creating the lattice cores of these sandwich structures. Experimental evaluation of the mechanical response of lattice cell structures (LCSs) is expensive in time and materials. As such, the finite element analysis (FEA) can be used to predict the mechanical behavior of LCSs with many different design variations more economically. Though there have been several reports on the use of FEA to develop models for predicting the post-yielding stages of 3D-printed LCSs, they are still insufficient to be a more general purpose due to the limitations associated with the lattice prediction behavior of specific features, certain geometries, and common materials along with showing sometimes poor prediction due to the computationally cheap elements out of which these models have been composed in most cases. This study focuses on the response of different LCSs at post-yielding stages based on the hexahedral elements to capture accurately the behaviors of 3D-printed polymeric lattices made of the Acrylonitrile Butadiene Styrene material. For this reason, three types of lattices such as body centered cubic, tetrahedron with horizontal struts, and pyramidal are considered. The FEA models are developed to capture the post-yielding compressive behavior of these different LCSs. These models are used to understand and provide detailed information of the failure mechanisms and relation between post-yielding deformations and the topologies of the lattice. All of these configurations were tested before experimentally during compression in the z-direction under quasi-static conditions and are compared here with the FEA results. The post-yielding behavior obtained from FEA matches reasonably well with the experimental observations, providing the validity of the FEA models.
Psychological and Neural Differences of Music Processing in Autistic Individuals: A Scoping Review
Authors: Hernandez-Ruiz Eugenia , Qi Ruowen , Welsh Emily , Wampler Madelyn , Bradshaw Liesel
Published: January 2022

Despite abundant research and clinical evidence of the effectiveness of music interventions for people in the autism spectrum, understanding of music processing in this community is limited. We explored whether research evidence of differences in music processing within the autistic community is available. We developed a scoping review to search for literature with the terms “music”, “processing,” and “autism” (and variants). We searched PubMed, CINAHL, Scopus, Web of Science, PsycInfo, Academic Search Complete, ERIC, and Music Index databases for a total of 10,857 articles, with 5,236 duplicates. The remaining 5,621 titles and abstracts were screened for eligibility by a team of four undergraduate and graduate students and the PI. Seventy-five studies were included for data extraction. Data were analyzed with descriptive statistics regarding author, study, stimulus, and participant information, and a thematic analysis of outcome and findings. Our findings are preliminary given the emerging nature of the literature, the use of mostly non-musical auditory stimuli, passive listening experiences, and underreported demographics. However, the literature shows some evidence of differences in music processing for autistic individuals, including reduced habituation to non-musical and musical stimuli; truncated, delayed, or divergent developmental trajectories; and possible compensatory higher-order mechanisms that yield similar behavioral responses even in the presence of divergent neural correlates. Music therapists are encouraged to adopt a developmental perspective, not only of general skills, but specifically of music skill development in this community, and to extrapolate these findings with caution, given the current limitations in the evidence.
The mechanical properties and fatigue responses of fiber metal nanocomposite laminates with double-edged cracks
Authors: Jen Ming-Hwa R , Hsu Li-Jen , Liang Yu-Cheng , Wu Ying-Hui
Published: January 2022

The fiber metal laminates (FMLs) of hybrid Ti/APC-2 neat and nanocomposite laminates were fabricated. Geometrically symmetric and anti-symmetric double-edged cracks were cut in FMLs. From tensile tests, we received the load vs. displacement curves, stress intensity factors of mixed mode and mechanical properties. From cyclic tests, the load vs. cycles (P–N) curves, residual life and failure mechanisms were obtained. The mechanical properties of symmetrically cracked specimens were slightly lower than those of anti-symmetrically cracked counterparts. As the crack length increases and inclination angle decreases, the fatigue life decreases. The enhancement of nanopowder improved the ultimate load and fatigue life. The local stress intensity at the crack tip dominates the fatigue responses. The piece of elliptical part was observed from cyclic tests at failure. Although the attraction of two crack tips accelerated the crack growth towards each other, the delay to failure was caused by two crack tips circling around and forming a small piece of ellipse centrally.
The poetics of togetherness: Conviviality of asylum-seekers in the shadow of Hong Kong
Authors: Cheng Sealing
Published: January 2022

This article examines the radical politics of a fragile togetherness on the margins of the state. A small but diverse group of long-term asylum-seekers found themselves in a decade-long limbo in Hong Kong, confronting an increasingly hostile border regime, and met regularly to ‘do something as a group’. Despite the lack of any breakthrough and advice to break away as individual cases, they have persisted in staying ‘as a group’. Drawing on participant observation with the group, Our Lives Matter, the article analyzes the ways these protracted asylum-seekers relate to each other as social beings, the mutuality and togetherness they cultivate, and the political possibilities opened up by such interconnections. Building on the scholarship of conviviality that examines ‘togetherness-in-differnece’, I develop the concept of poetics of togetherness to understand these asylum-seekers’ conviviality as practice, ethics, and a method of being otherwise on the margins, invariably dialoguing with, disavowing, and defying the center. Could conviviality as ethical and political projects create radical alternatives? The poetics of togetherness recognizes the precarity and divisiveness on the margins, while attending to the power of sociality and interdependence, and emergent forms of engagement. The simultaneous making of social and political agents opens up alternative possibilities of being, relating, and acting in the shadow of state violence. We gain insights into the dynamics between ‘margins’ and ‘center’ by understanding these practices and ethics of communality as political and epistemic projects to challenge and possibly transform uneven power dynamics and exclusionary structures.
Subjective Measures of Workload and Sleep in Australian Army Recruits; Potential Utility as Monitoring Tools
Authors: Gibson Neil , Drain Jace R , Larsen Penelope , Williams Sean , Groeller Herbert , Sampson John A
Published: January 2022

Introduction

Subjective measures may offer practitioners a relatively simple method to monitor recruit responses to basic military training (BMT). Yet, a lack of agreement between subjective and objective measures may presents a problem to practitioners wishing to implement subjective monitoring strategies. This study therefore aims to examine associations between subjective and objective measures of workload and sleep in Australian Army recruits.

Materials and Methods

Thirty recruits provided daily rating of perceived exertion (RPE) and differential RPE (d-RPE) for breathlessness and leg muscle exertion each evening. Daily internal workloads determined via heart rate monitors were expressed as Edwards training impulse (TRIMP) and average heart rate. External workloads were determined via global positioning system (PlayerLoadTM) and activity monitors (step count). Subjective sleep quality and duration was monitored in 29 different recruits via a customized questionnaire. Activity monitors assessed objective sleep measures. Linear mixed-models assessed associations between objective and subjective measures. Akaike Information Criterion assessed if the inclusion of d-RPE measures resulted in a more parsimonious model. Mean bias, typical error of the estimate (TEE) and within-subject repeated measures correlations examined agreement between subjective and objective sleep duration.

Results

Conditional R2 for associations between objective and subjective workloads ranged from 0.18 to 0.78, P < 0.01, with strong associations between subjective measures of workload and TRIMP (0.65–0.78), average heart rate (0.57–0.73), and PlayerLoadTM (0.54–0.68). Including d-RPE lowered Akaike Information Criterion. The slope estimate between objective and subjective measures of sleep quality was not significant. A trivial relationship (r = 0.12; CI −0.03, 0.27) was observed between objective and subjective sleep duration with subjective measures overestimating (mean bias 25 min) sleep duration (TEE 41 min).

Conclusions

Daily RPE offers a proxy measure of internal workload in Australian Army recruits; however, the current subjective sleep questionnaire should not be considered a proxy measure of objective sleep measures.
NGC 1850 BH1 is another stripped-star binary masquerading as a black hole
Authors: El-Badry Kareem , Burdge Kevin B
Published: January 2022

We show that the radial velocity variable star in the black hole (BH) candidate NGC 1850 BH1 cannot be a normal ${\approx}5\hbox{-}{\rm M}_{\odot }$ subgiant, as was proposed, but is an overluminous stripped-envelope star with mass ≈1 M⊙. The result follows directly from the star’s observed radius and the orbital period–density relation for Roche lobe-filling stars: The star’s density, as constrained by the observed ellipsoidal variability, is too low for its mass to exceed ${\approx}1.5\, {\rm M}_{\odot }$. This lower mass significantly reduces the implied mass of the unseen companion and qualitative interpretation of the system, such that a normal main-sequence companion with mass $2.5\!-\!5\, {\rm M}_{\odot }$ is fully consistent with the data. We explore evolutionary scenarios that could produce the binary using mesa and find that its properties can be matched by models in which an ${\approx}5\hbox{-}{\rm M}_{\odot }$ primary loses most of its envelope to a companion and is observed in a bloated state before contracting to become a core helium burning sdOB star. This is similar to the scenario proposed to explain the binaries LB-1 and HR 6819. Though it likely does not contain a BH, NGC 1850 BH1 provides an interesting test case for binary evolution models, particularly given its membership in a cluster of known age.
What Happened before Losses of Photosynthesis in Cryptophyte Algae?
Authors: Suzuki Shigekatsu , Matsuzaki Ryo , Yamaguchi Haruyo , Kawachi Masanobu
Published: January 2022

In many lineages of algae and land plants, photosynthesis was lost multiple times independently. Comparative analyses of photosynthetic and secondary nonphotosynthetic relatives have revealed the essential functions of plastids, beyond photosynthesis. However, evolutionary triggers and processes that drive the loss of photosynthesis remain unknown. Cryptophytes are microalgae with complex plastids derived from a red alga. They include several secondary nonphotosynthetic species with closely related photosynthetic taxa. In this study, we found that a cryptophyte, Cryptomonas borealis, is in a stage just prior to the loss of photosynthesis. Cryptomonas borealis was mixotrophic, possessed photosynthetic activity, and grew independent of light. The plastid genome of C. borealis had distinct features, including increases of group II introns with mobility, frequent genome rearrangements, incomplete loss of inverted repeats, and abundant small/medium/large-sized structural variants. These features provide insight into the evolutionary process leading to the loss of photosynthesis.
SIOP Ependymoma I: Final results, long-term follow-up, and molecular analysis of the trial cohort—A BIOMECA Consortium Study
Authors: Ritzmann Timothy A , Chapman Rebecca J , Kilday John-Paul , Thorp Nicola , Modena Piergiorgio , Dineen Robert A , Macarthur Donald , Mallucci Conor , Jaspan Timothy , Pajtler Kristian W , Giagnacovo Marzia , Jacques Thomas S , Paine Simon M L , Ellison David W , Bouffet Eric , Grundy Richard G
Published: January 2022

Background

SIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) of non-metastatic intracranial ependymoma in children aged 3–21 years treated with a staged management strategy. A further aim was to assess the response rate (RR) of subtotally resected (STR) ependymoma to vincristine, etoposide, and cyclophosphamide (VEC). We report final results with 12-year follow-up and post hoc analyses of recently described biomarkers.

Methods

Seventy-four participants were eligible. Children with gross total resection (GTR) received radiotherapy, whilst those with STR received VEC before radiotherapy. DNA methylation, 1q, hTERT, ReLA, Tenascin-C, H3K27me3, and pAKT status were evaluated.

Results

Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. GTR was achieved in 33/74 (44.6%) and associated with improved EFS (P = .003, HR = 2.6, 95% confidence interval (CI) 1.4–5.1). Grade 3 tumours were associated with worse OS (P = .005, HR = 2.8, 95%CI 1.3–5.8). 1q gain and hTERT expression were associated with poorer EFS (P = .003, HR = 2.70, 95%CI 1.49–6.10 and P = .014, HR = 5.8, 95%CI 1.2–28) and H3K27me3 loss with worse OS (P = .003, HR = 4.6, 95%CI 1.5–13.2). Methylation profiles showed expected patterns. 12 participants with STR did not receive chemotherapy; a protocol violation. However, best chemotherapy RR was 65.5% (19/29, 95%CI 45.7–82.1), exceeding the prespecified 45%.

Conclusions

Participants with totally resected ependymoma had the best outcomes. RR of STR to VEC exceeded the pre-specified efficacy criterion. However, cases of inaccurate stratification highlighted the need for rapid central review. 1q gain, H3K27me3 loss, and hTERT expression were all associated with poorer survival outcomes.
Migration and growth in a Schumpeterian growth model with creative destruction
Authors: Parello Carmelo Pierpaolo
Published: January 2022

This paper incorporates endogenous migration into a second-generation Schumpeterian growth model to study how migration, innovation, and growth interact with one another. The paper finds that migration always enhances the rates of innovation and growth of the receiving economy, but implementing pro-innovation policies in the receiving economy does not lead to more migration when the gap in technical knowledge between countries is fixed over time. However, when the technology gap is allowed to adjust endogenously, the paper finds that implementing pro-innovation policies in the receiving economy shrinks immigration flows and reduces the cross-country gap of technology.
Sovereign Risk, Currency Risk, and Corporate Balance Sheets
Authors: Du Wenxin , Schreger Jesse
Published: January 2022

We provide a comprehensive account of the evolution of the currency composition of sovereign and corporate external borrowing by emerging markets from 2003 to 2017. We show that a higher reliance on foreign currency debt by the corporate sector is associated with higher sovereign default risk. We introduce local currency sovereign debt and private sector currency mismatch into a standard sovereign debt model to examine how the currency composition of corporate borrowing affects the sovereign’s incentive to inflate or default. A calibration of the model generates the empirical patterns of sovereign credit risk.
Antipsychotic-Induced Weight Gain: Dose-Response Meta-Analysis of Randomized Controlled Trials
Authors: Wu Hui , Siafis Spyridon , Hamza Tasnim , Schneider-Thoma Johannes , Davis John M , Salanti Georgia , Leucht Stefan
Published: January 2022

Background

Weight gain is among the most important side-effects of antipsychotics. It is, however, unclear whether it is associated with antipsychotic doses. We aimed to fill this gap with a dose-response meta-analysis.

Methods

We searched multiple electronic databases (last update search June 2021) for all fixed-dose studies that investigated 16 second-generation antipsychotics and haloperidol in adults with acute exacerbation of schizophrenia or with negative symptoms. We estimated the dose-response curves by conducting random-effects dose-response meta-analyses. We used the restricted cubic spline to model the dose-response relationship. The primary outcome was mean weight gain in kg from baseline to endpoint, the secondary outcome was the number of patients with clinically important weight gain.

Findings

Ninety-seven studies with 333 dose arms (36 326 participants) provided data for meta-analyses. Most studies were short-term with median duration of 6 weeks (range 4 to 26 weeks). In patients with acute exacerbation, amisulpride, aripiprazole, brexpiprazole, cariprazine, haloperidol, lumateperone, and lurasidone produced mild weight gain in comparison to placebo (mean difference at any dose≤1 kg), while more significant weight gain was observed by all other drugs. For most drugs, dose-response curves showed an initial dose-related increase in weight which plateaued at higher doses, while for others there was no plateau and some even had bell-shaped curves, meaning less weight gain to be associated with higher doses.

Interpretation

Second-generation antipsychotics do not only differ in their propensity to produce weight gain, but also in the shapes of their dose-response curves. This information is important for dosing decisions in clinical practice.
Optimal spindle detection parameters for predicting cognitive performance
Authors: Adra Noor , Sun Haoqi , Ganglberger Wolfgang , Ye Elissa M , Dümmer Lisa W , Tesh Ryan A , Westmeijer Mike , Cardoso Madalena Da Silva , Kitchener Erin , Ouyang An , Salinas Joel , Rosand Jonathan , Cash Sydney S , Thomas Robert J , Westover M Brandon
Published: January 2022

Study Objectives

Alterations in sleep spindles have been linked to cognitive impairment. This finding has contributed to a growing interest in identifying sleep-based biomarkers of cognition and neurodegeneration, including sleep spindles. However, flexibility surrounding spindle definitions and algorithm parameter settings present a methodological challenge. The aim of this study was to characterize how spindle detection parameter settings influence the association between spindle features and cognition and to identify parameters with the strongest association with cognition.

Methods

Adult patients (n = 167, 49 ± 18 years) completed the NIH Toolbox Cognition Battery after undergoing overnight diagnostic polysomnography recordings for suspected sleep disorders. We explored 1000 combinations across seven parameters in Luna, an open-source spindle detector, and used four features of detected spindles (amplitude, density, duration, and peak frequency) to fit linear multiple regression models to predict cognitive scores.

Results

Spindle features (amplitude, density, duration, and mean frequency) were associated with the ability to predict raw fluid cognition scores (r = 0.503) and age-adjusted fluid cognition scores (r = 0.315) with the best spindle parameters. Fast spindle features generally showed better performance relative to slow spindle features. Spindle features weakly predicted total cognition and poorly predicted crystallized cognition regardless of parameter settings.

Conclusions

Our exploration of spindle detection parameters identified optimal parameters for studies of fluid cognition and revealed the role of parameter interactions for both slow and fast spindles. Our findings support sleep spindles as a sleep-based biomarker of fluid cognition.
Bounds of diversity: queer zoology in Europe from Aristotle to John Hunter
Authors: Brooks Ross
Published: January 2022

Zoological narratives of intersexualities (‘hermaphroditism’), transformations of sex and same-sex sexual behaviours have long played significant roles in shaping ideas about sex more generally, for good and for bad. Eclectic references to sex-variant animals in classical and medieval texts traverse nebulous boundaries between fact and fantasy. Only slowly through the early modern era did observation supersede superstition. The discovery by English naturalist John Ray in 1660, that all slugs and snails were dual-sexed, situated hermaphroditism as an integral concern of naturalists as never before. Through the 1770s and 1780s, Scottish anatomist John Hunter inaugurated a new era in the medico-scientific study of sex, establishing intersexualities and transformations of sex as primary means of theorizing sex differences more broadly but delineating an overly sharp division between ‘natural’ and ‘unnatural’ hermaphrodites. He even suggested, albeit briefly, how the division of sexes from hermaphrodite origins might have happened biologically, a question that was subsequently pursued by evolutionists including Erasmus Darwin and Charles Darwin. In contrast, zoological descriptions of same-sex sexual behaviours were published only rarely prior to the 19th century, a prevailing misunderstanding that animals did not engage in such behaviours playing important roles in shaping ‘natural law’ and Christian theology.
COVID-19 and Latinx Disparities: Highlighting the Need for Medical Schools to Consider Accepting DACA Recipients
Authors: Lucio Francisco
Published: January 2022

COVID-19 revealed and magnified the preexisting health inequities faced by many vulnerable groups. The Latinx community is one of these groups and has borne the brunt of disparate rates of infection, hospitalization, and mortality associated with COVID-19. These disparities are rooted in social inequities, such as poverty and lack of access to health care, as well as health inequities associated with disparate disease and condition burdens. Moreover, the lack of an adequate Latinx physician workforce contributes to and exacerbates these inequities. The COVID-19 pandemic has intersected with the U.S. Supreme Court’s decision in the Department of Homeland Security v. Regents of the University of California case. The court’s decision in this case struck down the attempted ending of the Deferred Action for Childhood Arrivals (DACA) program, although it was settled that the government could end the program if it was done lawfully. Even though this constitutes a win for DACA recipients, the decision is a stopgap as the future of DACA recipients remains vulnerable and subject to other legal challenges and political vagaries. In a time when the need to ameliorate health inequities for the Latinx community is so pronounced, DACA recipient medical trainees could provide much-needed relief. Since the implementation of DACA, some medical schools have decided to accept DACA recipient students, but many do not. This access-limiting practice stymies a group of potential trainees who could help to increase the Latinx physician workforce, as the majority of DACA recipients are Latinx. This article argues that all medical schools should take steps to consider accepting DACA recipient applicants in line with the principles of health equity and suggests 5 recommendations for medical school admissions, support, and advocacy practices.
Comparison of fixed versus adjustable-loop device for femoral graft fixation in anterior cruciate ligament reconstruction: a retrospective cohort study
Authors: Bagherifard Abolfazl , Jabalameli Mahmoud , Rahimi Fouad , Ghaderi Mohamad Taher , Kassir Hassan Assad , Naderi Nima
Published: January 2022

Background:

Fixed-loop and adjustable-loop are two types of cortical suspension devices that are used for graft fixation in anterior cruciate ligament reconstruction (ACLR). In this study, the authors compared clinical and functional outcomes of these devices in ACLR surgery.

Methods:

In a retrospective study, 60 patients who underwent ACLR using either fixed-loop (30 patients) or adjustable-loop were included. Clinical measures were Lachman test, pivot shift test, KT-1000, lack of extension, and flexion. Functional measures were 12-item Short-Form Health Survey, including the Physical Component Summary and the Mental Component Summary, International Knee Documentation Committee score, and Lysholm-Tegner activity scale.

Results:

The mean age of the patients was 31±7.5 yr. The mean follow-up of the patients was 18.5±6.4 mo. The grading of the Lachman test, pivot shift test, and KT-1000 were not significantly different between the study groups (P=0.47, P=1, and P=0.6, respectively). Lack of extension and flexion were not significantly different between the study groups (P=0.79 and P=0.28, respectively). The Physical Component Summary, Mental Component Summary, International Knee Documentation Committee, and Lysholm-Tegner activity scale were statistically comparable between the two study groups (P=0.46, P=0.68, P=0.55, P=0.77, respectively). Graft failure (KT>5 mm) was seen in seven patients (23.3%) of the fixed-loop group and four patients (13.3%) of the adjustable-loop group (P=0.31).

Conclusions:

Clinical and functional outcomes of fixed and adjustable-loop devices are comparable when used for femoral fixation in patients undergoing ACLR.

Level of Evidence:

Level IV.
Low Inadequate Oxygen Delivery Index is Associated with Decreased Cardiac Arrest Risk in High-Risk Pediatric ICU Patients
Authors: Dewan Maya , Cooper David S. , Tegtmeyer Ken
Published: January 2022

OBJECTIVES:

To evaluate the Inadequate Oxygen Delivery Index (IDO2) in the PICU to identify patients labeled as high risk by clinician concern who will not experience a cardiac arrest.

DESIGN, SETTING, AND PARTICIPANTS:

Prospective observational cohort study in a single PICU from February 1, 2017, to May 20, 2020. All mean calculated IDO2 was collected for patients in 12-hour increments.

MEASUREMENTS AND MAIN RESULTS:

We monitored 3,087 patients over 24,505 12-hour periods. Four thousand seventeen were watcher periods—12-hour period following watcher determination to watch for clinical deterioration. Overall, there were 224 clinical deterioration events of which 21% (n = 48) were cardiopulmonary resuscitation (CPR) events. Twenty-three CPR events (48%) and 93 clinical deteriorationevents (42%) occurred during 4,017 watcher periods. Following addition of a mean IDO2 threshold less than 5 during the prewatcher period, 23 CPR events (48%) and 77 clinical deterioration events (34%) occurred during 2,958 watcher periods. Using clinical concern alone, the number needed to evaluate for CPR events was 167 watcher periods for each single CPR event and 43 watcher periods for each clinical deterioration event. With the addition of a mean IDO2 less than 5, the number needed to evaluate decreased to 125 and 38, respectively, with no change in the prediction of CPR events.

CONCLUSIONS:

The use of physiologic monitor data can be applied to clinician-activated situation awareness systems to decrease the number needed to alert and improve system efficiency.
Out-of-the-ICU Mobilization in Critically Ill Patients: The Safety of a New Model of Rehabilitation
Authors: Sasano Nobuko , Kato Yuko , Tanaka Akemi , Kusama Nobuyoshi
Published: January 2022

OBJECTIVES:

Early mobilization of ICU patients has been reported to be safe and feasible. Recently, our ICU implemented out-of-the-ICU wheelchair excursions as a daily rehabilitation practice. The aim of this study is to investigate the safety of participation in the out-of-the-ICU program for early mobilization.

DESIGN:

Retrospective cohort study.

SETTING:

Single general ICU in a tertiary teaching hospital.

PATIENTS:

Adult patients who were admitted to the ICU and underwent the out-of-the-ICU program as an early mobilization intervention was investigated.

INTERVENTIONS:

The out-of-the-ICU activities include visiting indoor area, visiting our outdoor garden, and bathing.

MEASUREMENTS AND MAIN RESULTS:

Medical records of ICU patients who participated in the out-of-the-ICU program were reviewed. The primary outcome was the occurrence rate of physical safety events, defined as unintentional removal of medical devices, patient agitation, a fall, or an injury. The secondary outcome was the occurrence rate of adverse physiologic changes, defined as hypotension, hypertension, bradycardia, tachycardia, desaturation, bradypnea, tachypnea, an increase in Fio
2, or an increase in doses of vasoactive drugs. In total, 99 adult patients participated in the program, comprising a total of 423 out-of-the-ICU sessions. Among them, one session resulted in a physical safety event, the dislodgement of a tracheostomy tube. In 23 sessions, one or two adverse physiologic changes occurred. None of these events required additional treatment nor resulted in serious sequelae.

CONCLUSIONS:

An out-of-the-ICU program can be provided safely to adult ICU patients, provided that it is supervised by a dedicated intensivist with an appropriately trained multiprofessional staff and equipment on-site. It appears to contribute to the promotion of humanizing intensive care.
Chronic hypoperfusion due to intracranial large artery stenosis is not associated with cerebral β-amyloid deposition and brain atrophy
Authors: Fan Dongyu , Li Huiyun , Chen Dongwan , Chen Yang , Yi Xu , Yang Heng , Shi Qianqian , Jiao Fangyang , Tang Yi , Li Qiming , Wang Fangyang , Wang Shunan , Jin Rongbing , Zeng Fan , Wang Yanjiang
Published: January 2022

Background:

Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans.

Methods:

We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient.

Results:

The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47–76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion.

Conclusion:

Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.
Saikosaponin D Alleviates DOX-induced Cardiac Injury In Vivo and In Vitro
Authors: Zhang Yan-Jing , Wu Si-Si , Chen Xue-Mei , Pi Jin-Kui , Cheng Yu-Fei , Zhang Yi , Wang Xiao-Jiao , Luo Dan , Zhou Jin-Han , Xu Jia-Yi , Li Xue , Wu Zhuang , Jiang Wei , Wang Xiao-Xiao
Published: January 2022

As a highly efficient anticancer agent, doxorubicin (DOX) is used for treatment of various cancers, but DOX-induced oxidative damages contribute to a degenerative irreversible cardiac toxicity. Saikosaponin D (SSD), which is a triterpenoid saponin with many biological activities including anti-inflammatory effects and antioxidant properties, provides protection against pathologic cardiac remodeling and fibrosis. In the present study, we investigated the work of SSD for DOX-induced cardiotoxicity and the involved mechanisms. We observed that DOX injection induced cardiac injury and malfunction and decreased survival rate. Besides, DOX treatment increased lactate dehydrogenase leakage, cardiomyocyte apoptosis, and myocardium fibrosis and decreased the size of cardiomyocytes. Meanwhile, all the effects were notably attenuated by SSD treatment. In vitro, we found that 1 μM SSD could enhance the proliferation of H9c2 cells and inhibit DOX-induced apoptosis. It was found that the levels of malondialdehyde (MDA) and reactive oxygen species were significantly reduced by improving the activities of the endogenous antioxidative enzymes including catalase and glutathione peroxidase. Furthermore, SSD treatment could downregulate the DOX-induced p38 phosphorylation. Our results suggested that SSD efficiently protected the cardiomyocytes from DOX-induced cardiotoxicity by inhibiting the excessive oxidative stress via p38-MAPK (mitogen-activated protein kinase, MAPK) signaling pathway.
Ivabradine and Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials
Authors: Wang Zhongsu , Wang Weizong , Li Huilin , Zhang An , Han Yi , Wang Jiangrong , Hou Yinglong
Published: January 2022

This was a meta-analysis of randomized control trials (RCTs) to evaluate the effect of ivabradine on the risk of atrial fibrillation (AF) and its effect on the ventricular rate in patients with AF. The PubMed, EMBASE, Cochrane Controlled Trials Register, and other databases were searched for RCTs on ivabradine. Thirteen trials with 37,533 patients met the inclusion criteria. The incidence of AF was significantly higher in the ivabradine treatment group than in the control group [odds ratio (OR), 1.23; 95% confidence interval (CI), 1.08–1.41], although it was reduced after cardiac surgery (OR, 0.70; 95% CI, 0.23–2.12). Regarding left ventricular ejection fraction (LVEF), ivabradine increased the risk of AF in both LVEF >40% (OR, 1.42; 95% CI, 1.24–1.63) and LVEF ≤40% subgroups (OR, 1.16; 95% CI, 0.98–1.37). The risk of AF was increased by both small and large cumulative doses of ivabradine (small cumulative dose: OR, 3.00; 95% CI, 0.48–18.93; large cumulative dose: OR, 1.05; 95% CI, 0.83–1.34). Furthermore, ivabradine may reduce the ventricular rate in patients with AF. In conclusion, we found that both large and small cumulative doses of ivabradine were associated with an increased incidence of AF, and the effect was more marked in the LVEF >40% subgroup. Nevertheless, ivabradine therapy is beneficial for the prevention of postoperative AF. Furthermore, ivabradine may be effective in controlling the ventricular rate in patients with AF, although more RCTs are needed to support this conclusion.
Hesperetin Inhibits Sphingosylphosphorylcholine-Induced Vascular Smooth Muscle Contraction by Regulating the Fyn/Rho-Kinase Pathway
Authors: Lu Qian , Kishi Hiroko , Zhang Ying , Morita Tomoka , Kobayashi Sei
Published: January 2022

Cardiovascular diseases are the leading cause of mortality and disability worldwide. We have previously found that sphingosylphosphorylcholine (SPC) is the key molecule leading to vasospasm. We have also identified the SPC/Src family protein tyrosine kinase Fyn/Rho-kinase (ROK) pathway as a novel signaling pathway for Ca2+ sensitization of vascular smooth muscle (VSM) contraction. This study aimed to investigate whether hesperetin can inhibit the SPC-induced contraction with little effect on 40 mM K+-induced Ca2+-dependent contraction and to elucidate the underlying mechanisms. Hesperetin significantly inhibited the SPC-induced contraction of porcine coronary artery smooth muscle strips with little effect on 40 mM K+-induced contraction. Hesperetin blocked the SPC-induced translocation of Fyn and ROK from the cytosol to the membrane in human coronary artery smooth muscle cells (HCASMCs). SPC decreased the phosphorylation level of Fyn at Y531 in both VSMs and HCASMCs and increased the phosphorylation levels of Fyn at Y420, myosin phosphatase target subunit 1 at T853, and myosin light chain (MLC) at S19 in both VSMs and HCASMCs, which were significantly suppressed by hesperetin. Our results indicate that hesperetin inhibits the SPC-induced contraction at least in part by suppressing the Fyn/ROK pathway, suggesting that hesperetin can be a novel drug to prevent and treat vasospasm.
Levosimendan and Continuous Outpatient Support With Inotropes in Patients With Advanced Heart Failure: A Single-Centre Descriptive Study
Authors: Yeung Timothy , Dagan Misha , Lankaputhra Malanka , Cieslik Luke , Warner Victoria , Leet Angeline , Hare James L. , Bergin Peter , Taylor Andrew J. , Kaye David M. , Patel Hitesh C.
Published: January 2022

To describe the use of levosimendan in a quaternary referral center with a dedicated heart failure service and compare its efficacy and safety to continuous outpatient support with inotropes (COSI) among patients with advanced heart failure (AHF) who require bridge-to-decision (BTD) or bridge-to-transplant (BTT) therapy. This study was a retrospective, single-center, descriptive study of patients with AHF who received either a single levosimendan infusion or COSI between 2018 and 2021. A total of 23 patients received a levosimendan infusion, and 14 were started on COSI. Three indications for levosimendan were identified: (1) to facilitate weaning of continuous inotropes, (2) to augment diuresis in cardiorenal syndrome, and (3) as first-line therapy for cardiogenic shock in selected patients. Eighty-three percent (19 of 23) of patients who received levosimendan survived to discharge, and there were few clinically significant adverse events. Overall survival at 12 months among patients who received levosimendan was 74%. No statistically significant difference in survival was observed at 12 months (P = 0.68) or beyond (P = 0.63) between patients who received levosimendan and were discharged with a plan for BTD or BTT and those who received COSI. Levosimendan is a safe and effective short-term therapy in AHF and offers comparable long-term survival to COSI in patients who require BTD or BTT therapy.
A Glucagon-like Peptide 1 Analog Protects Mitochondria and Attenuates Hypoxia–Reoxygenation Injury in Cultured Cardiomyocytes
Authors: Kobara Miyuki , Toba Hiroe , Nakata Tetsuo
Published: January 2022

Glucagon-like peptide 1 (GLP-1) analogs improve glycemic control in diabetes and protect the heart against ischemia–reperfusion injury. However, the mechanisms underlying this protection remain unclear. Mitochondria are essential for myocyte homeostasis. Therefore, we herein examined the effects of a GLP-1 analog on mitochondria after the hypoxia–reoxygenation of rat neonatal cultured cardiomyocytes. Cardiomyocytes were subjected to hypoxia for 5 hours followed by reoxygenation for 30 minutes in the presence or absence of exendin-4 (50 nmol/L), a GLP-1 analog. Hypoxia–reoxygenation increased lactate dehydrogenase and caspase-3 activities, indicators of lethal myocyte injury and apoptosis, respectively, and exendin-4 attenuated these increases. The content of ATP in myocytes decreased after hypoxia–reoxygenation but was preserved by exendin-4. The membrane potential and shape of mitochondria were assessed using a fluorescent probe. Exendin-4 attenuated the hypoxia–reoxygenation–induced disruption of the mitochondrial membrane potential and shortening. Mitochondrial quality control–related factors, such as optic atrophy protein 1, mitofusin 2, dynamin-related protein 1, and parkin, were examined by Western blotting. Exendin-4 significantly increased the expression of the fusion proteins, optic atrophy protein 1 and mitofusin 2, and decreased that of the mitophagy-related protein, parkin, without altering dynamin-related protein 1 expression levels. Exendin-4 also preserved Akt phosphorylation levels after hypoxia–reoxygenation, whereas wortmannin, an inhibitor of the phosphoinositide 3-kinase–Akt pathway, blunted exendin-4–induced myocyte protection and its effects on mitochondrial quality control factors. In conclusion, exendin-4 protected mitochondria by preserving the phosphorylation of Akt and fusion proteins, leading to the attenuation of hypoxia–reoxygenation–induced injury in cultured myocytes.
Prevalence and Perception of Intimate Partner Violence-Related Traumatic Brain Injury
Authors: Manoranjan Branavan , Scott Taryn , Szasz Olivia Paige , Bzovsky Sofia , O'Malley Lauren , Sprague Sheila , Perera Gihan , Bhandari Mohit , Turkstra Lyn S.
Published: January 2022

Background:

Traumatic brain injury (TBI) is a serious and often undiagnosed consequence of intimate partner violence (IPV). Data on prevalence of TBI among IPV survivors are emerging, but prevalence of IPV among patients presenting to TBI clinics is unknown. Identification of IPV is important to ensure patients with TBI receive appropriate intervention and referrals.

Objective:

To determine the proportion of women 18 years and older presenting to an acquired brain injury (ABI) clinic with confirmed or suspected concussion who reported experiencing IPV in the last 12 months or their lifetime.

Methods:

Single-center cross-sectional cohort study. Proportion of IPV-related TBI or head, neck, or facial) injuries were determined using a modified HELPS Brain Injury Screening Tool and the Neurobehavioral Symptom Inventory.

Results:

Of the 97 women approached, 50 were enrolled in the study. The average age was 46.1 years and 32 women (64.0%) reported a relationship history with a violent partner; 12-month prevalence of IPV was 26.5% and lifetime prevalence was 44.0%. Within their lifetime, all (44.0%) who reported an IPV history reported emotional abuse, 24.0% reported physical abuse, and 18.0% sexual abuse. HELPS responses indicated a high potential of lifetime IPV-related TBI for 29.2%, most commonly from being hit in the face or head (20.8%).

Conclusion:

Implementation of IPV screening in community-based ABI clinics is a pivotal step toward understanding the potential scope of TBI and addressing the wide range of somatic, cognitive, and affective symptoms experienced by IPV survivors. IPV screening also will lead to timely referral and follow-up and increase patient safety after discharge from rehabilitation.
Interobserver Agreement for Classifying Infections in Patients with Decompensated Cirrhosis Based on Centers for Disease Control and Prevention Criteria
Authors: Ren Haotang , Yao Junjie , Zhao Ruihong , Gong Kai , Sun Shanshan , Yu Xia , Shen Wei , Duan Jinnan , Sheng Jifang , Shi Yu
Published: January 2022

Background:

Bacterial infections are common in patients with decompensated cirrhosis, largely owing to bacterial translocation and cirrhosis-associated immune dysfunction. This study aims to determine the reliability for classifying infections in patients with decompensated cirrhosis based on the Centers for Disease Control and Prevention (CDC) criteria.

Methods:

The patients with decompensated cirrhosis with suspicious infection in a registered prospective cohort of cirrhosis from May 1, 2014 to February 25, 2015 in the ward of First Affiliated Hospital of Zhejiang University were retrospectively identified. Agreement assessment was conducted focusing on site of infection, the possibility of infection, and pathogens of infection on both system level and specific diagnosis level. A subgroup analysis was performed based on with/without acute-on-chronic liver failure (ACLF).

Results:

A total of 402 infectious episodes among 351 patients were enrolled for consistency analysis. The overall agreement for site of infection was 94% (378/402) (k = 0.90, 95% CI 0.86–0.94) on system level and 86% (346/402) (k = 0.84, 95% CI 0.80–0.88) on specific diagnosis level. On possibility of infection, the overall agreement was 81% (306/378) (weighted k = 0.71, 95% CI 0.65–0.77), with 84% (224/267) (weighted k = 0.75, 95% CI 0.63–0.87) in patients with ACLF and 80% (70/88) (weighted k = 0.68, 95% CI 0.60–0.76) in patients without ACLF, respectively. On pathogens of infection, the overall agreement was 72% (60/83) (k = 0.70, 95% CI 0.60–0.80) among most frequent infections.

Conclusion:

The agreement for classifying infections in patients with decompensated cirrhosis based on CDC criteria is acceptable overall, suggesting that it can be a useful tool for clinical management in patients with decompensated cirrhosis with suspicious infections.
Advances in Therapy for Atopic Dermatitis
Authors: Zhou Nina , Bilimoria Sara , Lio Peter A.
Published: January 2022

Atopic dermatitis (AD) is the most common chronic inflammatory skin condition in the world, characterized by epidermal barrier dysfunction, increased pathogen ingress, dysbiosis, and chronic inflammation. Patients with AD are at an increased risk of other comorbidities including skin infections, sleep disorders, and psychosocial morbidities that have significant impacts on quality of life and warrant more advanced therapeutics. A number of Th2 cytokines and the JAK-STAT pathway have been identified as playing critical roles in the pathogenesis of AD resulting in a rich pipeline of agents that target these factors.

In this brief clinical review, we examine the evidence available for novel agents in Phase II and Phase III studies as potential treatments to broaden the therapeutic options, especially for patients with moderate-to-severe AD.
Epidermolysis Bullosa Simplex
Authors: Sadighi Tammy , Swayne Cheryl
Published: January 2022

Epidermolysis bullosa simplex (EBS) is a rare autosomal dominant, genetic condition where bullous lesions, larger than 0.5 cm, affect an area of the skin that is exposed to mechanical friction or minor trauma. Prevention of the bullous lesions starts with family and patient education, with infants requiring greater care and control of their environment. Every individual with EBS will have a treatment plan specifically tailored to the severity and extent of skin involvement. This article provides a comprehensive overview of EBS, including diagnostic approach, preventative considerations, and current treatments.