bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping the Moral Terrain of Clinical Deception
Authors: Brummett Abram , Salter Erica K.
Published: February 2023

Legal precedent, professional‐society statements, and even many medical ethicists agree that some situations may call for a clinician to engage in an act of lying or nonlying deception of a patient or patient's family member. Still, the moral terrain of clinical deception is largely uncharted, and when it comes to practical guidance for clinicians, many might think that ethicists offer nothing more than the rule never to deceive. This guidance is insufficient to meet the real‐world demands of clinical practice, and this article endeavors to articulate a framework to help clinicians better navigate the ethics of clinical deceit. The framework articulates four morally relevant dimensions of a potential deceptive act that should be examined to better determine the moral justification that might be required: the target of the act, the nature of the information, the nature of the act, and the context of the act.
Deception, Pain, and Placebo: Applying the Brummett‐Salter Deception Framework
Authors: Wasserman Jason Adam
Published: February 2023

In this commentary, I explore the usefulness of the framework Abram Brummett and Erica K. Salter present in their article “Mapping the Moral Terrain of Clinical Deception.” Deception cases are divisive because they nearly always evoke the metadilemma of clinical ethics: a clash between duties (in these cases, truth telling) and consequences (whatever good might come of the lie). Here, I describe a patient case in which the clinical team considered deceiving a patient about his pain‐medicine dosage in exchange for his allowing the clinicians to properly care for his percutaneous endoscopic gastrostomy tube stoma, so as to prevent infection. Applying the framework that Brummett and Salter have developed helped our clinical team parse the numerous complex issues involved. The nuances of our case also illustrated additional ways in which the ethics of deception needs to be further refined.
Distressed Work: Chronic Imperatives and Distress in Covid‐19 Critical Care
Authors: Navuluri Neelima , Solomon Harris S. , Hargett Charles W. , Kussin Peter S.
Published: February 2023

This ethnographic study introduces the term “distressed work” to describe the emergence of chronic frictions between moral imperatives for health care workers to keep working and the dramatic increase in distress during the Covid‐19 pandemic. Interviews and observant participation conducted in a hospital intensive care unit during the Covid‐19 pandemic reveal how health care workers connected job duties with extraordinary emotional, physical, and moral burdens. We explore tensions between perceived obligations of health care professionals and the structural contexts of work. Key findings cluster around the moral imperatives of health care work and the distress that work engendered as work spaces, senses of vocation, patient and family interactions, and end‐of‐life care shifted. While the danger of working beyond limits has long been an ordinary feature of health care work, it has now become a chronic crisis. Assessing this problem in terms of distressed work and its structural contexts can better address effective, worker‐informed responses to current health care labor dilemmas.
Reproducibility of cerebral perfusion measurements using BOLD delay
Authors: Khalil Ahmed A. , Tanritanir Ayse C. , Grittner Ulrike , Kirilina Evgeniya , Villringer Arno , Fiebach Jochen B. , Mekle Ralf
Published: February 2023

BOLD delay is an emerging, noninvasive method for assessing cerebral perfusion that does not require the use of intravenous contrast agents and is thus particularly suited for longitudinal monitoring. In this study, we assess the reproducibility of BOLD delay using data from 136 subjects with normal cerebral perfusion scanned on two separate occasions with scanners, sequence parameters, and intervals between scans varying between subjects. The effects of various factors on the reproducibility of BOLD delay, defined here as the differences in BOLD delay values between the scanning sessions, were investigated using a linear mixed model. Reproducibility was additionally assessed using the intraclass correlation coefficient of BOLD delay between sessions. Reproducibility was highest in the posterior cerebral artery territory. The mean BOLD delay test–retest difference after accounting for the aforementioned factors was 1.2 s (95% CI = 1.0 to 1.4 s). Overall, BOLD delay shows good reproducibility, but care should be taken when interpreting longitudinal BOLD delay changes that are either very small or are located in certain brain regions.
Swallowing analysis in hemi‐tongue reconstruction using motor‐innervated free flaps: A cine‐magnetic resonance imaging study
Authors: Kim Young Chul , Lee Seok Joon , Park Hojin , Choi Young Jun , Jeong Woo Shik , Lee Yoon Se , Choi Kyoung Hyo , Oh Tae Suk , Choi Jong Woo
Published: February 2023

Background

This study aimed to explore the outcomes of motor‐innervated free flaps in hemi‐tongue reconstruction by assessing the tongue mobility through midsagittal images from cine‐magnetic resonance imaging.

Methods

In this retrospective study, 47 patients who underwent tongue reconstruction following hemi‐glossectomy and 10 control subjects without any surgical history were included. Patients were classified into two groups: the motor and no‐motor innervation group. Various spatial parameters related to tongue mobility that were acquired from midsagittal sections were compared during consecutive swallowing phases.

Results

Overall, the motor group showed improved functional swallowing scale compared with the no‐motor group. In case of tongue base resection, the motor group showed improved mobility of the tongue base during pharyngeal phase, whereas the no‐motor group showed increased laryngeal elevation for compensatory movement.

Conclusion

The tongue reconstruction with motor‐innervated free flaps may facilitate swallowing capacity in patients with a hemi‐tongue defect combined with tongue base resection.
From Bolsonaro to Lula: The opportunity to rebuild universal healthcare in Brazil in the government transition
Authors: Chioro Arthur , Gomes Temporão José , Massuda Adriano , Costa Humberto , Castro Marcia C. , Lima Nísia Trindade de
Published: February 2023

This paper takes the government transition that took place between 2022 and 2023 in Brazil as a case study and aims to analyse how a cycle of radical right‐wing populist government acted to dismantle Brazil's national health system foundations. It describes how governance was built based on political‐clientelism and market‐privatising interests and on the adoption of long‐term fiscal austerity policies, whose results are public defunding and weakening and disorganisation of the country's national health system, with a significant worsening of health indicators and the capacity to respond to the population health needs. The lessons from recent experience in Brazil should serve as learning and a source of academic and political reflection, since there is an ongoing international movement and signs of rise of radical right‐wing populist regimes in several countries, which endanger the Democratic Rule of Law, institutions, and social policies. It allows putting into perspective how political cycles of this nature can affect national universal health systems, including those that have experienced substantial progress towards universal access and universal health coverage. Keeping in mind the Brazilian experience, it was possible to observe the progressive structuring of a radical right‐wing neo‐populism and in the sanitarian.
Forty‐seven year trend of measles in Iran: An interrupted time series analysis
Authors: Alimohamadi Yousef , Sepandi Mojtaba
Published: February 2023

Background and Aim

Measles is an acute viral infectious disease usually characterized by erythematous maculopapular rash and sometimes pneumonia, diarrhea, and Central Nervous System disturbance. The current study aimed to describe the trend of measles in Iran before and after the 1978 revolution and COVID‐19 pandemic.

Methods

In the current quasi‐experimental study, we used annual data on confirmed cases of measles in Iran, from 1974 to 2021. Data were extracted from the World Health Organization website. An interrupted time series model was used to assess the effect of different events on the incidence of measles.

Results

The trend of new cases increase every year until 1980 according to the preintervention slope of 2040 (95% confidence interval [CI] = −1965–2045; p < 0.31). After Iran's revolution, the occurrence of new cases significantly decreased (−845 [95% CI = −1262 to −432; p = 0.001]). After the COVID‐19 pandemic, the trend of new cases significantly increased (41 [95% CI = 12–70; p = 0.006]).

Conclusion

It seems that social or health‐related events are among the effective factors on the incidence of measles. But with maintaining vaccination coverage in the community and vaccination of immigrants, this fluctuation in the disease trend can be decreased.
eaQTLdb: An atlas of enhancer activity quantitative trait loci across cancer types
Authors: Yuan Jiapei , Tong Yang , Liu Xiaochuan , Li Mulin Jun , Zhang Qiang , Yang Yang
Published: February 2023

Enhancers are key regulatory elements that exert crucial roles in diverse biological processes, including tumorigenesis and cancer development. Active enhancers could produce transcripts termed enhancer RNAs (eRNAs), which could be used as an index of enhancer activity. Here, we present a versatile data portal, enhancer activity quantitative trait loci database (eaQTLdb; http://www.bioailab.com:3838/eaQTLdb), for exploring the effects of genetic variants on enhancer activity and prioritizing candidate variants across different cancer types. By leveraging the accumulated multiomics data, we systematically identified genetic variants which influence enhancer activity in different cancer types, termed as eaQTLs. We have linked the eaQTLs to hallmarks of cancer and patients' overall survival to illustrate their potential biological roles in cancer development and progression. Notably, eaQTLs associated with the infiltration abundance of 24 different immune cell types were identified and incorporated into eaQTLdb. In addition, we applied colocalization analyses to examine 59 complex diseases and traits to identify eaQTLs colocalized with diseases/traits GWAS signals. Overall, eaQTLdb, incorporating a rich resource for exploration of eaQTLs in different cancer types, will not only benefit users in prioritizing candidate genetic variants and enhancers, but also help researchers decipher the roles of eaQTLs in the dysregulated pathways of cancer and tumor immune microenvironment, opening new diagnostic and therapeutic avenues in precise medicine.
An exploration of parenting styles, cultural values, and infant development in a sample of Latin American immigrants in Canada
Authors: Hamel Kayla , Abdelmaseh Marette , Bohr Yvonne
Published: February 2023

The objective of the current research was to investigate the relationship between parenting style, culture, and infant development in a sample of Latin American mother‐infant dyads in Toronto, Canada. We examined associations between mothers’ self‐reported parenting style and infant cognitive and socioemotional development, which we compared to results from mothers belonging to two other Canadian immigrant populations. We further examined whether specific cultural correlates, including affiliation with traditional Latinx cultural beliefs familism and fatalism and acculturation, were associated with positive parenting behaviors in the Latin American sample. Across all three cultural groups, authoritative parenting predicted adaptive socio‐emotional development, an effect which differed in magnitude across groups, providing support for the hypothesis that the effect of parenting behaviors on infant development are moderated by culture. Within the Latin American sample, affiliation with the value of familism was associated with higher scores of authoritative parenting, but familism decreased as acculturation to the host culture increased. This research adds to our understanding of factors that contribute to the well‐being of Latin American families in Canada. Findings carry implications for provision of infant mental health services to Latin American immigrant families by identifying cultural variables which should be considered when providing parenting interventions to make such interventions more culturally relevant.
Research and scholarly methods: Measuring medication adherence
Authors: Shah Kanya K. , Touchette Daniel R. , Marrs Joel C.
Published: February 2023

Medication adherence is the extent to which a patient follows prescribed directions when taking a medication. Research examining interventions relating to medication adherence is becoming increasingly important for payers, providers, and researchers to inform clinical practice and utilization policies for medications. Multiple methods exist for measuring medication adherence, and the choice of methodology should be based on research design, data availability, and study aims. In this review, common methods for measuring medication adherence in retrospective studies using claims‐based data, prospective studies using data collected by the research team in real‐time, and patient/caregiver/clinician reported approaches using survey/interview data are discussed to facilitate research and review of studies involving medication adherence. For retrospective studies, this review discusses metrics designed to calculate medication adherence based on fills or dispense dates and days supplied. Such metrics include medication possession ratio (MPR) and proportion of days covered (PDC). A brief introduction of measuring adherence to multiple medications and group‐based trajectory modeling (GBTM) is included. For assessing adherence in prospective studies, a discussion on objective observational methods, such as pill counts and therapeutic drug monitoring and specialized pill bottle or cap devices, is covered. Lastly, for studies assessing patient/caregiver/clinician reported outcomes, a discussion of how diaries, interviews, and surveys/questionnaires/interviews can be used to measure medication adherence is reviewed.
Use of the benchmark‐dose (BMD) approach to derive occupational exposure limits (OELs) for genotoxic carcinogens: N‐nitrosamines
Authors: Blum Kamila , FitzGerald Rex , Wilks Martin F. , Barle Ester Lovsin , Hopf Nancy B.
Published: February 2023

N‐Nitrosamines are potent carcinogens and considered non‐threshold carcinogens in various regulatory domains. However, recent data indicate the existence of a threshold for genotoxicity, which can be adequately demonstrated. This aspect has a critical impact on selecting the methodology that is applied to derive occupational exposure limits (OELs). OELs are used to protect workers potentially exposed to various chemicals by supporting the selection of appropriate control measures and ultimately reducing the risk of occupational cancer. Occupational exposures to nitrosamines occur during manufacturing processes, mainly in the rubber and chemical industry. The present study derives OELs for inhaled N‐nitrosamines, employing the benchmark dose (BMD) approach if data are adequate and read‐across for nitrosamines without adequate data. Additionally, benchmark dose lower confidence limit (BMDL) is preferred and more suitable point‐of‐departure (PoD) to calculate human health guidance values, including OEL. The lowest OEL (0.2 μg/m3) was derived for nitrosodiethylamine (NDEA), and nitrosopiperidine (NPIP) (OEL = 0.2 μg/m3), followed by nitrosopyrrolidine (NPYR) (0.4 μg/m3), nitrosodimethylamine (NDMA), nitrosodimethylamine (NMEA), and nitrosodipropylamine (NDPA) (0.5 μg/m3), nitrosomorpholine (NMOR) (OEL = 1 μg/m3), and nitrosodibutylamine (NDBA) (OEL = 2.5 μg/m3). Limits based on “non‐threshold” TD50 slope calculation were within a 10‐fold range. These proposed OELs do not consider skin absorption of nitrosamines, which is also a possible route of entry into the body, nor oral or other environmental sources. Furthermore, we recommend setting a limit for total nitrosamines based on the occupational exposure scenario and potency of components.
3D printed wound constructs for skin tissue engineering: A systematic review in experimental animal models
Authors: de Souza Amanda , Martignago Cintia Cristina Santi , Santo Giovanna do Espirito , Sousa Karolyne dos Santos Jorge , Cruz Matheus Almeida , Amaral Gustavo Oliva , Parisi Julia Risso , Estadella Débora , Ribeiro Daniel Araki , Granito Renata Neves , Renno Ana Claudia Muniz
Published: February 2023

Wound dressings are one of the most used treatments for chronic wounds. Moreover, 3D printing has been emerging as a promising strategy for printing 3D printed wound constructs, being able of manufacturing multi layers, with a solid 3D structure. Although all these promising effects of 3D printed wound constructs, there is still few studies and limited understanding of the interaction of these dressings with skin tissue and their effect on the process of skin wound healing. In this context, the aim of this work was to perform a systematic review of the literature to examine the effects of 3D printed wound constructs on the process of skin wound healing in animal models. The articles were selected from three databases following Medical Subject Headings (MeSH) descriptors “3D printing,” “skin,” “wound,” and “in vivo.” After the selection, exclusion and inclusion criteria, nine articles were analyzed. This review confirms the significant benefits of using 3D printed wound constructs for skin repair and regeneration. All the used inks demonstrated the ability of mimicking the structure of skin tissue and promoting cell adhesion, proliferation, migration, and mobility. Furthermore, in vivo findings showed full wound closure in most of the studies, with well‐organized dermal and epidermal layers.
Profiling ambivalence in the context of nonsuicidal self‐injury
Authors: Gray Nicole , Uren Hannah , Pemberton Ethan , Boyes Mark
Published: February 2023

Background

We aimed to identify profiles of ambivalence among individuals with a history of non‐suicidal self‐injury (NSSI) and tested whether profiles differed across various theoretically informed constructs: NSSI‐related characteristics, cognitive (outcome expectancies, self‐efficacy to resist NSSI), emotional (psychological distress, difficulties in emotion regulation), personality, and incentives to engage/not engage in NSSI.

Methods

Individuals with a lifetime history of NSSI (n = 224) reported the extent to which they wanted to and did not want to engage in NSSI and completed well‐validated measures of the constructs of interest.

Results

Latent profile analysis indicated four ambivalence profiles (avoid: n = 39; moderately ambivalent: n = 85; highly ambivalent: n = 30; approach: n = 70). The profiles differed across a number of NSSI‐related characteristics, cognitive, emotional, and incentive‐related variables. Differences between the ambivalence profiles and the avoid/approach profiles varied across constructs. For example, the ambivalence and approach profiles were similar for NSSI‐related outcome expectancies, but the ambivalence and avoidance profiles were similar for self‐efficacy to resist NSSI.

Conclusion

Findings highlight variation between the desire to engage or not engage in NSSI that are consistent with the notion of ambivalence. Understanding these differences may allow for a more person‐centered approach in treatment for NSSI.
A randomized controlled trial of enhanced mentoring program practices for children of incarcerated caregivers: Assessing impacts on youth and match outcomes
Authors: Stelter Rebecca L. , Stump Kathryn N. , Rhodes Jean E. , Kupersmidt Janis B.
Published: February 2023

Parental incarceration is an adverse childhood experience that is associated with heightened risk for negative outcomes in youth. Mentoring programs seek to mitigate this risk by providing children of incarcerated parents (COIP) with a supportive relationship that fosters positive outcomes. The current study presents findings from a longitudinal evaluation of enhanced mentoring program practices designed for supporting COIP. One thousand three hundred and thirty‐four COIP mentees, their parents or guardians, and their mentors were randomly assigned to receive either enhanced or business as usual (BAU) mentoring. Mentees who received enhanced mentoring demonstrated improved positive self‐cognitions, and reduced internalizing behavior problems, intentions to use substances, and substance use, compared with youth who received BAU mentoring. The enhancements had no impact on the quality of mentoring relationships and the enhanced matches had shorter mentoring relationships compared with BAU matches. This evaluation demonstrates that the enhanced mentoring program practices for COIP had significant, positive impacts on outcomes for this special population of youth and suggests that enhanced practices tailored to COIP should be implemented throughout the duration of the mentoring relationship to be most effective.
Do program practices matter for mentors?: How implementation of empirically supported program practices is associated with youth mentoring relationship quality
Authors: Keller Thomas E. , Drew Alison L. , Herrera Carla , Clark‐Shim Hyuny , Spencer Renée
Published: February 2023

This study investigates how the implementation of program‐level practices by formal youth mentoring programs is associated with the quality of youth mentoring relationships as contexts for youth development and also examines whether this connection is mediated by the mentor‐staff working alliance. Using data from mentors (n = 542) participating in multiple programs (n = 55), multilevel path models examined hypothesized direct and mediated effects. Parallel analyses were conducted with assessments of program practices from staff (n = 219). Greater exposure to program practices was associated with higher ratings of mentoring relationship satisfaction, commitment, and security and lower mentor‐youth relationship negativity. The mentor‐staff working alliance either partially or fully mediated these associations. Staff‐reported practices predicted mentoring relationship satisfaction and commitment without mediation by the working alliance. This study suggests program practices contribute to stronger youth mentoring relationships. The findings also highlight the mentor‐staff working alliance in supporting the development of positive mentoring relationships.
First responder perceptions of the system of care and people who use drugs: Spanning boundaries
Authors: Mendoza Natasha S. , Holmes Tasha
Published: February 2023

Addressing the beliefs of first responders about people who use drugs and the system of care with which they interact must be part and parcel to addressing the opioid crisis. Using a boundary spanning framework, we examine how first responders perceive community behavioral health. With qualitative methods, we asked: What are first responders' lived experiences on the frontlines of the opioid crisis? In sum, it is important to consider that there is a critical role that first responders could play in brokering services when they are not themselves behavioral health practitioners but are, importantly, boundary spanners.
Design, synthesis, and biological evaluation of 1,4,7,8‐tetrahydro‐5H‐furo[3,4‐b]pyrazolo[4,3‐e]pyridin‐5‐one‐based azo dyes
Authors: Kamaloddin‐Ezabadi Seyed Fakhreddin , Mahmoodi Nosrat O. , Mamaghani Manouchehr , Pasandideh‐Nadamani Meysam
Published: February 2023

Some 1,4,7,8‐tetrahydro‐5H‐furo[3,4‐b]pyrazolo[4,3‐e]pyridin‐5‐ones containing azo group were synthesized by a three‐component one‐pot reaction of a preformed azoaldehyde (AZA), tetronic acid, and 5‐aminopyrazole in ethanol in the presence of triethylamine under microwave irradiation. The structures of the products were confirmed by spectroscopic data. This method has the advantages of simpler operation to prepare a new dihydropyridines (1,4‐DHPs) ring with multi‐functional groups architecture, high efficiency, short reaction time, and exciting atom economical chemistry. All the products were evaluated regarding antibacterial activities. Some compounds exhibited potent antibacterial activity against both Gram‐negative (Escherichia coli) and Gram‐positive (Micrococcus luteus and Staphylococcus aureus) bacteria compared with erythromycin and tetracycline. The antioxidant activity (AOA) of the synthesized compounds was considered in comparison to vitamin C. Some compounds exhibited the highest AOA, even higher than vitamin C.
A second case of glutaminase hyperactivity: Expanding the phenotype with epilepsy
Authors: Rumping Lynne , Pouwels Petra J. W. , Wolf Nicole I. , Rehmann Holger , Wamelink Mirjam M. C. , Waisfisz Quinten , Jans Judith J. M. , Prinsen Hubertus C. M. T. , van de Kamp Jiddeke M. , van Hasselt Peter M.
Published: February 2023

Glutaminase (GLS) hyperactivity was first described in 2019 in a patient with profound developmental delay and infantile cataract. Here, we describe a 4‐year‐old boy with GLS hyperactivity due to a de novo heterozygous missense variant in GLS, detected by trio whole exome sequencing. This boy also exhibits developmental delay without dysmorphic features, but does not have cataract. Additionally, he suffers from epilepsy with tonic clonic seizures. In line with the findings in the previously described patient with GLS hyperactivity, in vivo 3 T magnetic resonance spectroscopy (MRS) of the brain revealed an increased glutamate/glutamine ratio. This increased ratio was also found in urine with UPLC‐MS/MS, however, inconsistently. This case indicates that the phenotypic spectrum evoked by GLS hyperactivity may include epilepsy. Clarifying this phenotypic spectrum is of importance for the prognosis and identification of these patients. The combination of phenotyping, genetic testing, and metabolic diagnostics with brain MRS and in urine is essential to identify new patients with GLS hyperactivity and to further extend the phenotypic spectrum of this disease.
Characterizing Streamline Count Invariant Graph Measures of Structural Connectomes
Authors: Newlin Nancy R. , Rheault François , Schilling Kurt G. , Landman Bennett A.
Published: February 2023

Background

While graph measures are used increasingly to characterize human connectomes, uncertainty remains in how to use these metrics in a quantitative and reproducible manner. Specifically, there is a lack of community consensus regarding the number of streamlines needed to generate connectomes.

Purpose

The purpose was to define the relationship between streamline count and graph‐measure value, reproducibility, and repeatability.

Study Type

Retrospective analysis of previously prospective study.

Population

Ten healthy subjects, 70% female, aged 25.3 ± 5.9 years.

Field Strength/Sequence

A 3‐T, T1‐weighted sequences and diffusion‐weighted imaging (DWI) with two gradient strengths (b‐values = 1200 and 3000 sec/mm2, echo time [TE] = 68 msec, repetition time [TR] = 5.4 seconds, 120 slices, field of view = 188 mm2).

Assessment

A total of 13 graph‐theory measures were derived for each subject by generating probabilistic whole‐brain tractography from DWI and mapping the structural connectivity to connectomes. The streamline count invariance from changes in mean, repeatability, and reproducibility were derived.

Statistical Tests

Paired t‐test with P value <0.05 was used to compare graph‐measure means with a reference, intraclass correlation coefficient (ICC) to measure repeatability, and concordance correlation coefficient (CCC) to measure reproducibility.

Results

Modularity and global efficiency converged to their reference mean with ICC > 0.90 and CCC > 0.99. Edge count, small‐worldness, randomness, and average betweenness centrality converged to the reference mean, with ICC > 0.90 and CCC > 0.95. Assortativity and average participation coefficient converged with ICC > 0.75 and CCC > 0.90. Density, average node strength, average node degree, characteristic path length, average local efficiency, and average clustering coefficient did not converge, though had ICC > 0.90 and CCC > 0.99. For these measures, alternate definitions that converge a reference mean are provided.

Data Conclusion

Modularity and global efficiency are streamline count invariant for greater than 6 million and 100,000 streamlines, respectively. Density, average node strength, average node degree, characteristic path length, average local efficiency, and average clustering coefficient were strongly dependent on streamline count.

Evidence Level

1.

Technical Efficacy

Stage 1.
Sulforaphane is a reversible covalent inhibitor of 3‐chymotrypsin‐like protease of SARS‐CoV‐2
Authors: Chen Zinuo , Du Ruikun , Cooper Laura , Achi Jazmin G. , Dong Meiyue , Ran Yan , Zhang Jiwei , Zhan Peng , Rong Lijun , Cui Qinghua
Published: February 2023

The ongoing pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has posed a major public health threat worldwide and emphasizes an urgent need for effective therapeutics. Recently, Ordonez et al. identified sulforaphane (SFN) as a novel coronavirus inhibitor both in vitro and in mice, but the mechanism of action remains elusive. In this study, we independently discovered SFN for its inhibitory effect against SARS‐CoV‐2 using a target‐based screening approach, identifying the viral 3‐chymotrypsin‐like protease (3CLpro) as a target of SFN. Mechanistically, SFN inhibits 3CLpro in a reversible, mixed‐type manner. Moreover, enzymatic kinetics studies reveal that SFN is a slow‐binding inhibitor, following a two‐step interaction. Initially, an encounter complex forms by specific binding of SFN to the active pocket of 3CLpro; subsequently, the isothiocyanate group of SFN as “warhead” reacts covalently to the catalytic cysteine in a slower velocity, stabilizing the SFN‐3CLpro complex. Our study has identified a new lead of the covalent 3CLpro inhibitors which has potential to be developed as a therapeutic agent to treat SARS‐CoV‐2 infection.
Nucleos(t)ide analogues altered quasispecies composition of hepatitis B virus (HBV)‐resistant mutations in serum HBV DNA and serum HBV RNA
Authors: Liao Hao , Zhang He , Shao Jinman , Li Xiaoyong , Zheng Wei V. , Li Le , Yu Guangxin , Si Lanlan , Zhou Tao , Yao Zengtao , Dai Jiuzeng , Xu Dongping , Cheng Guanxun , Qu Jiuxin , Liu Yan , Chen Junhui , Lu Fengmin
Published: February 2023

Serum hepatitis B virus (HBV) RNA is a new serological indicator reflecting viral replication with good clinical application prospects. This study aimed to clarify the dynamic changes of serum HBV RNA levels and the quasispecies of HBV RNA virus‐like particles in nucleos(t)ide analogues (NAs)‐experienced chronic hepatitis B (CHB) patients harboring NAs‐resistant mutations and their identifiable effects on NAs resistance. We included CHB patients who were on long‐term NAs treatment and with HBV DNA rebound. The longitudinally dynamics of serum HBV RNA levels were quantitatively detected, and the quasispecies differences between serum HBV DNA and serum HBV RNA were compared by high‐throughput sequencing. The effect of NAs concentration pressure on altering the resistance mutations quasispecies proportion of HBV DNA and HBV RNA in cell supernatant was analyzed in vitro. A total of 447 serum samples from 36 CHB patients treated with NAs were collected. The median follow‐up period was 47 months (about 4 years), and the longest follow‐up period was 117 months (about 10 years). Our results showed that HBV RNA could reflect virological breakthrough in 23 (64%, 23/36) patients, and serum HBV RNA rebound earlier than HBV DNA in 12 (52%, 12/23) patients. However, serum HBV RNA remained at a consistently high level and did not fluctuate significantly with the HBV DNA rebound in 6 of 36 patients. In addition, serum HBV RNA was not consistently detectable in 7 of the 36 patients, and their serum HBV RNA was undetectable even after HBV DNA had rebounded. The proportion of drug‐resistant mutations in HBV DNA was higher than that of HBV RNA by high‐throughput sequencing. The results of in vitro experiments showed that the viral strains with drug‐resistant mutation in HBV DNA in cell supernatants gradually become the dominant strains with the increase of NAs concentrations. Serum HBV RNA levels can reflect virological breakthrough in most NAs‐ treated CHB patients, but there are certain limitations. NAs alter the quasispecies composition of serum HBV DNA and serum HBV RNA, resulting in a higher detection rate of drug‐resistant mutations in serum HBV DNA than in serum HBV RNA.
Human coronavirus 3CL proteases cleave septins and disrupt Hedgehog signaling, causing ciliary dysfunction
Authors: Lee Ah Reum , Kweon Yeong Cheon , Lee Sang Min , Park Chan Young
Published: February 2023

Coronaviruses target ciliate cells causing the loss of cilia, acute rhinorrheas, and other ciliopathies. The loss of ciliary function may help the virus infect, replicate, and spread. However, the molecular mechanisms by which coronaviruses cause ciliary defects are still unclear. Herein we demonstrate how coronavirus infection and severe acute respiratory syndrome coronavirus2 3CL protease induce cilia dysfunction by targeting a host protein septin that is required for the structure and function of cilia. Further, we demonstrate that coronaviruses and 3CL protease lead to the cleavage of several septin proteins (SEPT2, ‐6, and ‐9), producing cleaved obstructive fragments. Furthermore, ectopic expression of cleaved SEPT2 fragments shows defective ciliogenesis, disoriented septin filaments, and ablated Sonic Hedgehog (SHH) signaling in a protease activity‐dependent manner. We present that the 3CLpro inhibitors are potent and prevent abnormal ciliary structures and SHH signaling. These results provide useful insights into the general mechanisms underlying ciliary defects caused by coronaviruses, which, in turn, facilitate virus spread and prove that preclinical and clinical 3CL protease inhibitors may prove useful as therapeutics for treating ciliary defects of coronaviruses.
Effect of oat β‐glucan on gel properties and protein conformation of silver carp surimi
Authors: He Xueli , Lv Yanan , Li Xuepeng , Yi Shumin , Zhao Honglei , Xu Yongxia , Li Jianrong
Published: February 2023

BACKGROUND

Polysaccharides are the most widely used additives to enhance the quality of surimi gels. Oat β‐glucan (OG), a functional polysaccharide, is known to affect the gelation characteristics of surimi. However, it has been rarely reported. Therefore, the effect of OG at different levels on gelling properties, protein conformation, and microstructures of silver carp surimi gels were investigated.

RESULTS

An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. Moreover, the incorporation of OG (0–1.0%) facilitated the unfolding of proteins, resulting in the conformational transformation from α‐helix to β‐sheet and β‐turn. Consequently, surimi–OG gels displayed a denser network structure with smaller and more uniform voids. Furthermore, partial free water in the gel network was converted into immobile water, increasing the water‐holding capacity. However, a further increase in the OG concentration (1.0–2.0%) resulted in a looser and more uneven network structure with large and numerous cavities. In addition, the whiteness of composite gels decreased with increasing content of OG.

CONCLUSION

The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. © 2023 Society of Chemical Industry.
Different diagnostic approaches for the characterization of the fungal community and Fusarium species complex composition of Italian durum wheat grain and correlation with secondary metabolite accumulation
Authors: Senatore Maria Teresa , Prodi Antonio , Tini Francesco , Balmas Virgilio , Infantino Alessandro , Onofri Andrea , Cappelletti Eleonora , Oufensou Safa , Sulyok Michael , Covarelli Lorenzo , Beccari Giovanni
Published: February 2023

BACKGROUND

The evolution of the fungal communities associated with durum wheat was assessed using different diagnostic approaches. Durum wheat grain samples were collected in three different Italian cultivation macro‐areas (north, center and south). Fungal isolation was realized by potato dextrose agar (PDA) and by deep‐freezing blotter (DFB). Identification of Fusarium isolates obtained from PDA was achieved by partial tef1α sequencing (PDA + tef1α), while those obtained from DFB were identified from their morphological characteristics (DFB + mc). The fungal biomass of eight Fusarium species was quantified in grains by quantitative polymerase chain reaction (qPCR). Fungal secondary metabolites were analyzed in grains by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Correlations between Fusarium detection techniques (PDA + tef1α; DFB + mc and qPCR) and mycotoxins in grains were assessed.

RESULTS

Alternaria and Fusarium showed the highest incidence among the fungal genera developed from grains. Within the Fusarium community, PDA + tef1α highlighted that F. avenaceum and F. graminearum were the most represented members, while, DFB + mc detected a high presence of F. proliferatum. Alternaria and Fusarium mycotoxins, principally enniatins, were particularly present in the grain harvested in central Italy. Deoxynivalenol was mainly detected in northern‐central Italy.

CONCLUSIONS

The adoption of the different diagnostic techniques of Fusarium detection highlighted that, for some species, qPCR was the best method of predicting their mycotoxin contamination in grains. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Preparation and evaluation of astaxanthin‐loaded 2‐hydroxypropyl‐beta‐cyclodextrin and Soluplus® nanoparticles based on electrospray technology
Authors: Xue Yuanyuan , Liao Youwu , Wang Haiqiao , Li Shuang , Gu Zhengqing , Adu‐Frimpong Michael , Yu Jiangnan , Xu Ximing , Smyth Hugh D. C , Zhu Yuan
Published: February 2023

BACKGROUND

Astaxanthin is a type of food‐derived active ingredient with antioxidant, antidiabetic and non‐toxicity functions, but its poor solubility and low bioavailability hinder further application in food industry. In the present study, through inclusion technologies, micellar solubilization and electrospray techniques, we prepared astaxanthin nanoparticles before optimizing the formulation to regulate the physical and chemical properties of micelles. We accomplished the preparation of astaxanthin nanoparticle delivery system based on single needle electrospray technology through use of 2‐hydroxypropyl‐β‐cyclodextrin and Soluplus® to improveme the release behavior of the nanocarrier.

RESULTS

Through this experiment, we successfully prepared astaxanthin nanoparticles with a particle size of approximately 80 nm, which was further verified with scanning electron microscopy and transmission electron microscopy. Furthermore, the encapsulation of astaxanthin molecules into the carrier nanoparticles was verified via the results of attenuated total reflectance intensity and X‐ray powder diffraction techniques. The in vitro release behavior of astaxanthin nanoparticles was different in media that contained 0.5% Tween 80 (pH 1.2, 4.5 and 6.8) buffer solution and distilled water. Also, we carried out a pharmacokinetic study of astaxanthin nanoparticles, in which it was observed that astaxanthin nanoparticle showed an effect of immediate release and significant improved bioavailability.

CONCLUSION

2‐hydroxypropyl‐β‐cyclodextrin and Soluplus® were used in the present study as a hydrophilic nanocarrier that could provide a simple way of encapsulating natural function food with repsect to improving the solubility and bioavailability of poorly water‐soluble ingredients. © 2023 Society of Chemical Industry.
Non‐destructive discrimination of homochromatic foreign materials in cut tobacco based on VIS‐NIR hyperspectral imaging
Authors: Liang Jing , Wang Yueying , Shi Yu , Huang Xiaowei , Li Zhihua , Zhang Xinai , Zou Xiaobo , Shi Jiyong
Published: February 2023

BACKGROUND

The presence of foreign materials (FM) not only reduces the commercial value of tobacco and the quality of cigarette products, but also affects the aroma and flavor of cigarettes. Existing tobacco deblending equipment has received little study with respect to homochromatic FM. In the present study, visible‐near infrared (VIS‐NIR) hyperspectral imaging technique combined with chemometrics were used to identify and visualize the homochromatic FM on the surface of thining tobacco. A comparison with conventional vision method was made to analyze the feasibility of the method. The importance of detecting FM in cut tobacco was further demonstrated by first studying the volatile organic compounds produced in cigarette mixed FM smoke and their effects on human health before conducting hyperspectral experiments.

RESULTS

The results indicated that solid‐phase microextraction and gas chromatography mass spectrometry could detect volatile organic compounds in mainstream cigarette smoke that were not cigarette components and affected consumer health. Then, spectral features of the samples were extracted from hyperspectral images for building identification models to distinguish FM from cut tobacco. The visual RGB values of cut tobacco and FM were also used for the analysis of the recognition models. The results showed that the accuracy, precision and recall reached 100.00% using the back propagation artificial neural network classification model based on the principal component analysis raw wavelengths. The visualization results based on the optimal model produced clearer localization than conventional computer vision method.

CONCLUSION

The present study revealed that the VIS‐NIR hyperspectral imaging technology had advantage in the detection and localization of FM on the surface of thinning tobacco, which provided a foundation for improving the quality and safety of cut tobacco production. © 2023 Society of Chemical Industry.
Artificial intelligence to investigate predictors and prognostic impact of time to surgery in colon cancer
Authors: Alaimo Laura , Moazzam Zorays , Woldesenbet Selamawit , Lima Henrique A. , Endo Yutaka , Munir Muhammad M. , Azap Lovette , Ruzzenente Andrea , Guglielmi Alfredo , Pawlik Timothy M.
Published: February 2023

Background and Objectives

The role of time to surgery (TTS) for long‐term outcomes in colon cancer (CC) remains ill‐defined. We sought to utilize artificial intelligence (AI) to characterize the drivers of TTS and its prognostic impact.

Methods

The National Cancer Database was utilized to identify patients diagnosed with non‐metastatic CC between 2004 and 2018. AI models were employed to rank the importance of several sociodemographic, facility, and tumor characteristics in determining TTS, and postoperative survival.

Results

Among 518 983 patients, 137 902 (26.6%) received intraoperative diagnosis of CC (TTS = 0), while 381 081 (74.4%) underwent elective surgery (TTS > 0) with median TTS of 19.0 days (interquartile range [IQR]: 7.0−33.0). An AI model, identified tumor stage, receipt of adequate lymphadenectomy, histologic grade, lymphovascular invasion, and insurance status as the most important variables associated with TTS = 0. Conversely, the type and location of treating facility and receipt of adjuvant therapy were among the most important variables for TTS > 0. Notably, TTS was among the most important variables associated with survival, and TTS > 3 weeks was associated with an incremental increase in mortality risk.

Conclusions

The identification of factors associated with TTS can help stratify patients most likely to suffer poor outcomes due to prolonged TTS, as well as guide quality improvement initiatives related to timely surgical care.
Efficacy and Safety of Ultrasound‐Guided Percutaneous Ablation for Adrenal Metastases
Authors: Zhong Huohu , Wang Zecheng , Liu Yingchao , Ke Helin , Liu Piaopiao , Lian Xihua , Xu Zhenhong
Published: February 2023

Objectives

To assess the efficacy and safety of ultrasound‐guided percutaneous ablation (US‐PA) for adrenal metastases (AMs) using a meta‐analysis.

Methods

A systematic search of PubMed, Cochrane, Web of Science, and Embase electronic databases was performed to identify studies on US‐PA for AM. Seven studies published between January 2000 and August 2022 were analyzed, which resulted in a sample size of 140 patients. Both random effects and common effects meta‐analysis models were used to analyze the following efficacy and safety outcomes: the first and secondary technical success rate, 1‐year overall survival rates, 1‐year local tumor control rate, incidence rate of intraoperative hypertensive crises, and major complications. The subgroup analysis was performed to explore the origin of heterogeneity.

Results

Among 140 patients from 7 studies included in this meta‐analysis: 51 (36.43%) underwent radiofrequency ablation (RFA), and 89 (63.57%) underwent microwave ablation (MWA). Pooled data analysis revealed that the first and secondary technical success rates were 85% (95% confidence interval [CI], 73–96) and 99% (95% CI, 96–100), the 1‐year overall survival rate was 83% (95% CI, 71–93), the 1‐year local tumor control rate was 83% (95% CI, 75–90), and the incidence rate of intraoperative hypertensive crises was 14% (95% CI, 8–20). The overall rate of major complications was 3.6%. In the subgroup analysis, lower heterogeneity was indicated to be associated with mean tumor size and ablation type.

Conclusions

This meta‐analysis showed that US‐PA can be both effective and safe for AM in terms of overall survival, technical success rate, and local control for AM.
Pulmonary Congestion on Lung Ultrasound Predicts Increased Risk of 30‐Day Readmission in Heart Failure Patients
Authors: Cohen Allison , Li Timmy , Maybaum Simon , Fridman David , Gordon Miles , Shi Dorothy , Nelson Mathew , Stevens Gerin R.
Published: February 2023

Objectives

Heart failure exacerbations are a common cause of hospitalizations with a high readmission rate. There are few validated predictors of readmission after treatment for acute decompensated heart failure (ADHF). Lung ultrasound (LUS) is sensitive and specific in the assessment of pulmonary congestion; however, it is not frequently utilized to assess for congestion before discharge. This study assessed the association between number of B‐lines, on LUS, at patient discharge and risk of 30‐day readmission in patients hospitalized for acute decompensated heart failure (ADHF).

Methods

This was a single‐center prospective study of adults admitted to a quaternary care center with a diagnosis of ADHF. At the time of discharge, the patient received an 8‐zone LUS exam to evaluate for the presence of B‐lines. A zone was considered positive if ≥3 B‐lines was present. We assessed the risk of 30‐day readmission associated with the number of lung zones positive for B‐lines using a log‐binomial regression model.

Results

Based on data from 200 patients, the risk of 30‐day readmission in patients with 2–3 positive lung zones was 1.25 times higher (95% CI: 1.08–1.45), and in patients with 4–8 positive lung zones was 1.50 times higher (95% CI: 1.23–1.82, compared with patients with 0–1 positive zones, after adjusting for discharge blood urea nitrogen, creatinine, and hemoglobin.

Conclusion

Among patients admitted with ADHF, the presence of B‐lines at discharge was associated with a significantly increased risk of 30‐day readmission, with greater number of lung zones positive for B‐lines corresponding to higher risk.