bluuebunny/crossref_metadata_2025 huggingface dataset:
Before and After Hinckley
Authors: Morse Stephen J
Published: January 2023

This chapter first considers the scope of the affirmative defence of legal insanity in the United States before John Hinckley was acquitted by reason of insanity in 1982 for attempting to assassinate President Reagan and others and the immediate aftermath of that acquittal. Since the middle of the 20th century, the tale is one of the rise and fall of the American Law Institute’s Model Penal Code test for legal insanity. The chapter then turns to the constitutional decisions of the United States Supreme Court concerning the status of legal insanity. Finally, it addresses the substantive and procedural changes that have occurred in the insanity defence since the wave of legal changes following the Hinckley decision.
And Was Made Man
Authors: Le Poidevin Robin
Published: January 2023

The doctrine of the incarnation—that God became human in Christ—is one of the most astonishing propositions ever advanced, and it is at the heart of the Christian faith. It is also a paradoxical one, in that it immediately faces the objection that, since the properties of humanity and divinity are incompatible, nothing can be both divine and human. Can the doctrine be defended against the charge of incoherence? This is the central question of this book. It is a question which has received intense attention in recent philosophy of religion, but the distinctively novel features of this book are twofold. First, it brings a range of debates in contemporary metaphysics—in particular, debates over identity, persistence, composition, embodiment, essence, mind, space, time, and necessity—to bear on the central question. Second, it defends a particularly wide-ranging version of the view of the incarnation known as the kenotic model, on which God the Son gave up, in an act of kenosis or self-emptying, certain divine characteristics in order to become human. There are certain properties traditionally ascribed to God, such as being independent of time, being disembodied, existing of necessity, and being the ground of goodness, which it apparently makes no sense to suppose could be given up: they are, it seems, held by God timelessly or eternally. This book proposes a development of the kenotic model in which kenosis could coherently be thought to apply even to these apparently unchangeable aspects of the divine.
Kenosis
Authors: Le Poidevin Robin
Published: January 2023

The fourth incarnational model, which will be the focus for the rest of the book, is the kenotic model. The development of kenoticism is briefly traced through four different variants, but the main concern is with those variants which posit a self-emptying in terms of a giving up of certain characteristic divine properties by the Son in order to become incarnate. Seven key objections to kenoticism which have been advanced by critics are presented and responded to, before a further challenge is posed: that a full kenosis would require a series of impossible transformations concerning presence, immateriality, goodness, and time. Whether the transformations in question are truly impossible is the subject of Part II (Chapters 5–8).
Divine Embodiment
Authors: Le Poidevin Robin
Published: January 2023

What is it for God the Son to become embodied? Does that require the Son to give up the divine property of omnipresence? What would it be to give up such a property? And does becoming embodied require the transformation of an immaterial being into a material one? If not, what explains the Son’s exclusive relation to the body of Christ? If so, how would such a transformation be possible? For isn’t an object’s being material or immaterial essential to that object? These questions are explored in the context of different accounts of omnipresence (in terms of occupation, identity, and power), space (relationist versus substantivalist), and embodiment (causal versus realization). The kenotic model is best placed to explain the Son’s embodiment.
Introduction
Authors: Schobert Harold
Published: January 2023

Coal is in a time of great transition. Coal can, and has in the past, provide most of the underpinnings of a modern industrial society: heat, electricity, transportation, chemical products, and metals. However, its traditional uses are waning. Renewable energy forms are steadily dropping in cost. Environmental concerns are driving closures of mines and power plants. Some financial institutions will no longer invest in coal projects. For coal to have a viable future, it is time to rethink its uses and consider coal not as a fuel but as a source of chemicals and carbon materials.
Mining
Authors: Schobert Harold
Published: January 2023

Coal needs to be removed from the ground to be used. Two strategies are available: underground mining or surface mining. Underground mining hazards include dust, gases, and water. Chronic dust inhalation leads to various debilitating conditions such as black lung disease. Some of the gases found in mines are suffocating, poisonous, or explosive. Acidic water drained from mines is an environmental problem. Surface mining can lead to environmental degradation unless appropriate reclamation regulations are followed. Despite the long history of environmental impacts, injuries, and deaths, coal mining is a fairly safe application when workplace health and safety rules and mined land reclamation laws are observed. Coal could be used without mining it by converting it to gaseous fuels underground or by extracting methane from coal seams.
Electricity
Authors: Schobert Harold
Published: January 2023

Coals are important fuels for electricity generation. Their use is declining because of competition with natural gas and renewable energy, as well as concern for carbon dioxide emissions. Electricity is produced using steam turbines to turn a generator. Many fuels and combustion methods can be used to generate the steam. Coal-fired electricity generation usually relies on burning finely pulverized coal. The boilers contain large numbers of tubes through which steam passes. The amount of coal needed to generate a kilowatt of electric power is about half that needed a century ago. Fluidized-bed combustion provides an alternative to pulverized-coal firing. Combined-cycle plants burn natural gas in a gas turbine. The hot gases leaving the gas turbine are used to generate steam for a steam turbine. Both turbines operate generators, improving plant efficiency. Direct carbon fuel cells offer a simpler, “low-hardware” technology.
Environment
Authors: Schobert Harold
Published: January 2023

Any strategy for using coal for electricity generation has potentially significant impacts on the environment if steps are not taken to minimize emissions. Acid rain results from emissions of sulfur and nitrogen oxides produced during combustion. Reducing the sulfur content of the coal before it is burned or capturing sulfur oxides before they can be released are both helpful steps. Tiny ash particles suspended in the flue gases are captured by electrostatic precipitators or in baghouses. The hazardous trace element mercury can be controlled by adsorbing mercury vapors on activated carbon. A coal-fired power plant has greatly reduced emissions compared to plants of even a few decades ago. Because the dominant element in all coals is carbon, coal-fired plants will continue to emit large quantities of carbon dioxide. The carbon dioxide problem is the source of much of the pressure to reduce or eliminate the use of coal in electricity generation.
Coke
Authors: Schobert Harold
Published: January 2023

Using coals to produce coke, a fuel and reducing agent for metallurgical processes, is the second-largest application of coals, though small compared to the electricity market. Many bituminous coals soften, swell, and then resolidify when heated. The product is metallurgical coke, used worldwide in blast furnaces to produce iron. Producing a tonne of iron today requires only one-third the amount of coke used years ago, thanks to improvements in furnace technology. In the furnace, coke must react readily with the air blast, generate temperatures high enough to melt iron and slag, and yet retain enough strength to avoid being crushed by the great weight of ore, flux, and more coke above it. Sulfur and phosphorus are undesirable impurities in coke because they will enter the iron and affect its strength.
Retail Deterrence of Very High-Risk Groups
Authors: Braga Anthony A. , Cook Philip J.
Published: January 2023

Most shootings are highly concentrated among groups of criminally active individuals who use guns to settle disputes emanating from personal clashes, drug market business, ongoing gang rivalries, and other conflicts. Cities can diminish their overall gun violence problems by reducing violent victimization in these very high-risk groups through the strategic application of “carrots and sticks” or, more formally, incentives and disincentives. “Focused deterrence” programs designed to change offender behavior through a credible threat of law enforcement are effective in controlling crime. These programs gain legitimacy if coupled with social services and opportunities for targeted offenders, and they can help improve police–community relationships in disadvantaged minority communities. These multifaceted programs can be difficult to implement and sustain over extended periods. Jurisdictions must develop a strong network of willing partners, adopt accountability structures and sustainability plans, and conduct upfront and ongoing analyses of gun violence problems to customize the program to local conditions.
The anion channel SLAH3 interacts with potassium channels to regulate nitrogen–potassium homeostasis and the membrane potential in Arabidopsis
Authors: Liu Beibei , Feng Changxin , Fang Xianming , Ma Zhen , Xiao Chengbin , Zhang Shuaishuai , Liu Zhenzhen , Sun Doudou , Shi Hongyong , Ding Xiaoqin , Qiu Chenyang , Li Jia , Luan Sheng , Li Legong , He Kai
Published: January 2023

Nitrogen (N) and potassium (K) are essential macronutrients for plants. Sufficient N and K uptake from the environment is required for successful growth and development. However, how N and K influence each other at the molecular level in plants is largely unknown. In this study, we found loss-of-function mutation in SLAH3 (SLAC1 HOMOLOGUE 3), encoding a NO3− efflux channel in Arabidopsis thaliana, enhanced tolerance to high KNO3 concentrations. Surprisingly, slah3 mutants were less sensitive to high K+ but not NO3−. Addition of NO3− led to reduced phenotypic difference between wild-type and slah3 plants, suggesting SLAH3 orchestrates NO3−-K+ balance. Non-invasive Micro-test Technology analysis revealed reduced NO3− efflux and enhanced K+ efflux in slah3 mutants, demonstrating that SLAH3-mediated NO3− transport and SLAH3-affected K+ flux are critical in response to high K +. Further investigation showed that two K+ efflux channels, GORK (GATED OUTWARDLY-RECTIFYING K+ CHANNEL) and SKOR (STELAR K+ OUTWARD RECTIFIER), interacted with SLAH3 and played key roles in high K+ response. The gork and skor mutants were slightly more sensitive to high K+ conditions. Less depolarization occurred in slah3 mutants and enhanced depolarization was observed in gork and skor mutants upon K+ treatment, suggesting NO3−/K+ efflux-mediated membrane potential regulation is involved in high K+ response. Electrophysiological results showed that SLAH3 partially inhibited the activities of GORK and SKOR in Xenopus laevis oocytes. This study revealed that the anion channel SLAH3 interacts with the potassium channels GORK and SKOR to modulate membrane potential by coordinating N–K balance.
Exogenous Ca2+ promotes transcription factor phosphorylation to suppress ethylene biosynthesis in apple
Authors: Xu Yaxiu , Liu Zhi , Lv Tianxing , Wei Yun , Liu Weiting , Wei Yajing , Yang Guangxin , Liu Li , Li Tong , Wang Aide
Published: January 2023

Ethylene biosynthesis in apple (Malus domestica) fruit can be suppressed by calcium ions (Ca2+) during storage; however, the underlying mechanisms are unclear. In this study, we identified the apple transcription factor MCM1-AGAMOUS-DEFICIENS-SRF5 (MdMADS5), which functions as a transcriptional activator of the ethylene biosynthesis-related gene 1-AMINOCYCLOPROPANE-1-CARBOXYLIC ACID SYNTHASE1 (MdACS1), a partner of the calcium sensor CALCIUM-DEPENDENT PROTEIN KINASES7 (MdCDPK7). Ca2+ promoted the MdCDPK7-mediated phosphorylation of MdMADS5, which resulted in the degradation of MdMADS5 via the 26S proteasome pathway. MdCDPK7 also phosphorylated 1-AMINOCYCLOPROPANE-1-CARBOXYLIC ACID OXIDASE1 (MdACO1), the key enzyme in ethylene biosynthesis, leading to MdACO1 degradation and inhibition of ethylene biosynthesis. Our results reveal that Ca2+/MdCDPK7–MdMADS5 and Ca2+/MdCDPK7–MdACO1 are involved in Ca2+-suppressed ethylene biosynthesis, which delays apple fruit ripening. These findings provide insights into fruit ripening, which may lead to the development of strategies for extending the shelf life of fruit.
SL (2, ℤ) action on quantum field theories with U(1) subsystem symmetry
Authors: Yamaguchi Satoshi
Published: January 2023

We consider SL$(2,\mathbb {Z})$ action on quantum field theories with U(1) subsystem symmetry in five dimensions. This is an analog of the SL$(2,\mathbb {Z})$ action considered by E. Witten [From Fields to Strings: Circumnavigating Theoretical Physics: A Conference in Tribute to Ian Kogan, p. 1173 (2003) [arXiv:hep-th/0307041]]. We show that the exotic level-one BF theory and the exotic level-one Chern–Simons theories are trivial and almost trivial, respectively. By using this fact, we define the S operation and T operation. These operations give the SL$(2,\mathbb {Z})$ group up to a possible invertible phase that is unity within the spacetimes treated in this paper. We also demonstrate SL$(2,\mathbb {Z})$ action on the φ theory as an example.
Fractional topological charge in lattice Abelian gauge theory
Authors: Abe Motokazu , Morikawa Okuto , Suzuki Hiroshi
Published: January 2023

We construct a non-trivial $U(1)/\mathbb {Z}_q$ principal bundle on T4 from the compact U(1) lattice gauge field by generalizing Lüscher’s constriction so that the cocycle condition contains $\mathbb {Z}_q$ elements (the ’t Hooft flux). The construction requires an admissibility condition on lattice gauge field configurations. From the transition function so constructed, we have the fractional topological charge that is $\mathbb {Z}_q$ one-form gauge invariant and odd under the lattice time reversal transformation. Assuming a rescaling of the vacuum angle θ → qθ suggested from the Witten effect, our construction provides a lattice implementation of the mixed ’t Hooft anomaly between the $\mathbb {Z}_q$ one-form symmetry and the time reversal symmetry in the U(1) gauge theory with matter fields of charge $q\in 2\mathbb {Z}$ when θ = π, which was studied by Honda and Tanizaki [J. High Energy Phys. 12, 154 (2020)] in the continuum framework.
Analysis ofSOD1variants in Chinese patients with familial amyotrophic lateral sclerosis
Authors: Li H , Yuan L , Yang H , Guo Y , Zheng W , Fan K , Deng S , Gong L , Xu H , Yang Z , Cheng J , Kang M , Deng H
Published: January 2023

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, and genetic contributors exert a significant role in the complicated pathogenesis. Identification of the genetic causes in ALS families could be valuable for early diagnosis and management. The development of potential drugs for patients with genetic defects will shed new light on ALS therapy.

Aim

To identify causative variants in three Chinese families with familial ALS (FALS), reveal the pathogenic mechanism and look for the targeted drug for ALS.

Design and methods

Whole-exome sequencing and bioinformatics were used to perform genetic analysis of the ALS families. Functional analysis was performed to study the variants’ function and search for potential drug targets.

Results

Three heterozygous missense variants of the superoxide dismutase 1 gene (SOD1) were identified in families with FALS. The clinical manifestations of these patients include spinal onset, predominant lower motor neurons presentation and absence of cognitive involvement. Functional analysis showed that all three SOD1 variants led to increased reactive oxygen species (ROS) levels, reduced cell viability and formation of cytoplasmic aggregates. Remarkably, the decreased cell viability induced by variants was rescued after treatment with the ROS inhibitor N-acetylcysteine.

Conclusions

This study identified three SOD1 variants in three families with FALS. The variant SOD1 toxicity was associated with oxidative damage and aggregation, and N-acetylcysteine could rescue the decreased cell viability induced by these variants. Our findings support a pathogenic role for ROS in SOD1 deficiencies and provide a potential drug N-acetylcysteine for ALS therapy, especially in SOD1 patients with limb onset.
COVID-19 mRNA vaccine immunogenicity decay and breakthrough illness in adolescents and young adults with childhood-onset rheumatic diseases
Authors: Yeo Joo Guan , Teh Kai Liang , Chia Wan Ni , Book Yun Xin , Hoh Sook Fun , Gao Xiaocong , Das Lena , Zhang Jinyan , Sutamam Nursyuhadah , Poh Su Li , Lim Amanda Jin Mei , Tay Shi Huan , Yaung Katherine Nay , Ong Xin Mei , Leong Jing Yao , Wang Lin-Fa , Albani Salvatore , Arkachaisri Thaschawee
Published: January 2023

Objectives

To evaluate the humoral immunogenicity for 6 months after the two-dose coronavirus disease 2019 (COVID-19) mRNA vaccination in adolescents and young adults (AYAs) with childhood-onset rheumatic diseases (cRDs).

Methods

This monocentric observational study was conducted between August 2020 and March 2022. Humoral immunogenicity was assessed at 2–3 weeks after first vaccine dose and 1, 3 and 6 months after the second dose by the cPass™ severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralization antibody (nAb) assay. An inhibition signal of ≥30% defined the seroconversion threshold and the readings were calibrated against the World Health Organization International Standard for SARS-CoV-2 antibodies.

Results. One hundred and sixty-nine

AYAs with cRDs were recruited [median age 16.8 years (interquartile range, IQR 14.7–19.5), 52% female, 72% Chinese]. JIA (58%) and SLE (18%) comprised the major diagnoses. After second vaccine dose, 99% seroconverted with a median nAb titre of 1779.8 IU/ml (IQR 882.8–2541.9), declining to 935.6 IU/ml (IQR 261.0–1514.9) and 683.2 IU/ml (IQR 163.5–1400.5) at the 3- and 6-month timepoints, respectively. The diagnosis of JIA [odds ratio (OR) 10.1, 95% CI 1.8–58.4, P = 0.010] and treatment with anti-TNF-α (aTNF) (OR 10.1, 95% CI 1.5–70.0, P = 0.019) were independently associated with a >50% drop of nAb titres at 6 months. Withholding MTX or MMF did not affect the vaccine response or decay rate. The COVID-19 breakthrough infection was estimated at 18.2 cases/1000 patient-months with no clinical risk factors identified.

Conclusion

Over half of AYAs with cRDs had a significant drop in SARS-CoV-2 nAb at 6-month despite an initial robust humoral response. JIA and aTNF usage are predictors of a faster decay rate.
Urine proteomics by mass spectrometry identifies proteins involved in key pathogenic pathways in patients with juvenile dermatomyositis
Authors: Morales Melissa , Alayi Tchilabalo D , Tawalbeh Shefa M , Sydenstricker Agnes V , Spathis Rita , Kim Hanna , Nagaraju Kanneboyina , Hathout Yetrib , Rider Lisa G
Published: January 2023

Objectives

To identify and validate biomarkers in JDM patients using a multiplexing tandem mass tag urine proteome profiling approach.

Methods

First morning void urine samples were collected from JDM patients (n = 20) and healthy control subjects (n = 21) and processed for analysis using a standardized liquid chromatography-tandem mass spectrometry approach. Biomarkers with significantly altered levels were correlated with clinical measures of myositis disease activity and damage. A subset of candidate biomarkers was validated using commercially available ELISA kits.

Results

In total, 2348 proteins were detected in the samples, with 275 proteins quantified across all samples. Among the differentially altered proteins, cathepsin D and galectin-3 binding protein were significantly increased in the urine of JDM patients (adjusted P < 0.05), supporting previous findings in myositis patients. These two candidate biomarkers were confirmed with ELISAs. Cathepsin D positively correlated with Myositis Damage Index (r = 0.57, P < 0.05) and negatively correlated with the Childhood Myositis Assessment Scale (r = −0.54, P < 0.05). We also identified novel JDM candidate biomarkers involved with key features of myositis, including extracellular matrix remodelling proteins.

Conclusion

This study confirmed the presence of several proteins in the urine of JDM patients that were previously found to be elevated in the blood of myositis patients and identified novel candidate biomarkers that require validation. These results support the use of urine as a source for biomarker development in JDM.
Cannabis and male sexual health: contemporary qualitative review and insight into perspectives of young men on the internet
Authors: Shahinyan Gary K , Hu Ming-Yeah Y , Jiang Tommy , Osadchiy Vadim , Sigalos John T , Mills Jesse N , Kachroo Naveen , Eleswarapu Sriram V
Published: January 2023

Introduction

Cannabis use is increasing across the United States, yet its short- and long-term effects on sexual function remain controversial. Currently, there is a paucity of studies exploring the relationship between cannabis and men’s health.

Objectives

To summarize the available literature on cannabis and men’s health and provide insight into lay perceptions of this topic.

Methods

We performed a qualitative PubMed review of the existing literature on cannabis and men’s health according to the PRISMA guidelines. Separately, we analyzed relevant themes in online men’s health forums. We utilized a Google cloud–based platform (BigQuery) to extract relevant posts from 5 men’s health Reddit forums from August 2018 to August 2019. We conducted a qualitative thematic analysis of the posts and quantitatively analyzed them using natural language processing and a meaning extraction method with principal component analysis.

Results

Our literature review revealed a mix of animal and human studies demonstrating the negative effects of cannabis on semen parameters and varying effects on erectile function and hormone levels. In our analysis of 372 686 Reddit posts, 1190 (0.3%) included relevant discussion on cannabis and men’s health. An overall 272 posts were manually analyzed, showing that online discussions revolve around seeking answers and sharing the effects of cannabis on various aspects of sexual health and quality of life, often with conflicting experiences. Quantitative analysis revealed 1 thematic cluster related to cannabis, insecurity, and mental/physical health.

Conclusions

There is a limited number of quality human studies investigating the effects of cannabis on men’s health. Men online are uncertain about how cannabis affects their sexual health and seek more information. As the prevalence of cannabis use increases, so does the need for research in this area.
Lasiodiplodia regiae sp. nov.: A New Species Causing Canker and Dieback of Fruit Trees in China
Authors: Wang Yanfen , Xie Shunpei , Cao Jiayuan , Zhao Hang , Yin Xinming , Guo Yashuang , Xu Chao , Guo Lihua , Wu Haiyan , Zhang Meng
Published: January 2023

Canker and dieback are serious fungal diseases of woody plants that can cause huge economic losses to orchards. The purpose of this study was to classify and assess the pathogenicity of fungal species associated with canker and dieback on fruit trees growing in Henan Province, China. In total, 150 isolates of Botryosphaeriaceae were obtained from six different fruit trees exhibiting typical symptoms of stem canker, branch dieback, and gummosis. Morphological examinations and phylogenetic analysis of ITS, tef1, tub2, and rpb2 revealed two Botryosphaeriaceae species, which are Botryosphaeria dothidea and a novel species, Lasiodiplodia regiae, respectively. Using Koch's postulates, we confirmed that the different isolates of L. regiae can cause disease in their original hosts. The pathogenicity tests showed that L. regiae can cause canker, dieback, and gummosis symptoms in four different hosts, indicating a relatively wider host range. Moreover, 10 L. regiae isolates exhibited similar symptoms but different levels of virulence on shoots of peach trees under field conditions. This study demonstrated that L. regiae was a new causal agent of canker and dieback of six fruit tree species, which could be a serious risk to the orchard industry in China. Furthermore, the findings provide a foundation for further epidemiological studies and the development of management strategies.
Prescription Drug Misuse with Alcohol Coingestion among US Adolescents: Youth Experiences, Health-related Factors, and Other Substance Use Behaviors
Authors: Ford Jason A. , McCabe Sean Esteban , Schepis Ty S.
Published: January 2023

Background

While alcohol use and prescription drug misuse (PDM) are common among adolescents, there is relatively little research on coingestion. This is disquieting as polysubstance use has become a major contributing factor in drug overdose deaths among young people in the United States.

Methods

The current research uses multiple years of data from the National Survey on Drug Use and Health (2015–2019) to assess characteristics associated with coingestion among adolescents aged 12 to 17 years (N = 57,352). Multinomial logistic regression analysis is used to identify characteristics associated with past 30-day PDM with and without alcohol coingestion. The primary objective is to determine how youth experiences with parents, involvement in conventional activities, religiosity, social support, and school status are associated with coingestion.

Results

Among adolescents who report past 30-day PDM, 18.6% coingest with alcohol and 77.5% of adolescents who coingest report at least one substance use disorder. Several youth experiences were significantly associated with opioid coingestion including increased conflict with parents (relative risk ratio [RRR], 1.27; 95% confidence interval [CI], 1.07–1.48), lower levels of religiosity (RRR, 0.72; 95% CI, 0.52–0.98), less social support (RRR, 0.36; 95% CI, 0.18–0.69), and not being in school (RRR, 3.86; 95% CI, 1.33–11.17). In addition, emergency department visits, depression, and other substance use behaviors were also significantly associated with coingestion.

Conclusions

Findings demonstrate a strong connection between coingestion and substance use disorder among US adolescents. The findings from the current study can inform prevention and intervention efforts by identifying youth experiences and health-related factors that are associated with coingestion.
Resilient Mothering
Authors: Tuthill Emily L. , Maltby Ann E. , Odhiambo Belinda C. , Akama Eliud , Dawson-Rose Carol , Weiser Sheri D.
Published: January 2023

Efficacious strategies can now prevent the transmission of HIV from mother to child. However, transmission rates remain unacceptably high, especially in sub-Saharan Africa. Understanding women's perinatal transitions can inform interventions to support adherence to preventive strategies. Therefore, we applied Transitions Theory in a longitudinal qualitative study to explore perinatal transitions among women living with HIV in western Kenya. We conducted in-depth interviews with 30 women living with HIV at 3 key time points and, using our findings, described the theory's concepts in terms of participants' experiences. We then proposed theory-based interventions that could support smooth transition processes and positive outcomes.
Transition in the Context of Parental Participation in Caring for Infants in Neonatal Intensive Care Units
Authors: Oh Won-Oak , Lee Anna , Heo Yoo-Jin
Published: January 2023

While participating in the care for a baby in a neonatal intensive care unit, parents experience a transition in which they adapt to changes and reconstruct their roles and identities. However, there is no clear explanation for this concept of transition. The purpose of this study was to clarify this concept using Rodgers' evolutionary approach. The identified attributes of the concept were a process of learning, repeated undulating emotions, balancing a caring relationship with nurses, and embracing new roles and responsibilities. The findings can provide a knowledge base for future research aimed at enhancing nurses' understanding of transition and promoting parental participation.
Harmine suppresses the malignant phenotypes and PI3K activity in breast cancer
Authors: Yao Pengmei , Yao Penghua , Ku Xiaoxia , Yang Jing
Published: January 2023

Breast cancer remains a serious threaten to the women’s health, discovery of potent treatment would help to improve the outcomes of breast cancer patients. Harmine extracted from Peganum harmala L, has been reported to exert tumor suppressive activity in several malignancies. Our objective was to demonstrate the effects of harmine on the malignant phenotypes of breast cancer cells. Breast cancer cell lines (MDA-MB-231, SKBR3, and MCF-7) and human normal breast cell line MCF-10A were employed in the present study. The MTT and colony formation assays were applied to the detection of cell viability and proliferation. Wound healing and transwell assays were performed to evaluate the alterations of cell migration and invasion after harmine treatment. Flow cytometry was applied to assess the effect of harmine in inducing cell apoptosis. Furthermore, western blotting assay was used to detect the biomarkers of epithelial-mesenchymal transition and phosphatidylinositol 3 kinase (PI3K) signaling pathway. The tumorigenesis ability was detected by subcutaneous implantation. Harmine dose-dependently suppressed the viability and proliferative capacity of breast cancer cells. Flow cytometry showed that harmine induced apoptosis in MCF-7 and MDA-MB-231 cells. In addition, harmine effectively inhibited the migration and invasion abilities of breast cancer cells. Western blotting indicated harmine significantly promoted E-cadherin and PTEN expression, while suppressed N-cadherin, vimentin, PI3K, p-mTOR, and AKT levels. Interfering the PTEN expression by siRNA partly rescued the activity of PI3K signaling pathway. Moreover, harmine injection also suppressed the tumorigenesis of breast cancer cells. Our results suggested that Hermine could suppress multiple malignant phenotypes and inhibit PI3K signaling, which supports that harmine might be a potential tumor-suppressive natural compound against breast cancer.
Improving Postpartum and Long-Term Health After an Adverse Pregnancy Outcome: Examining Interventions From a Health Equity Perspective
Authors: DITOSTO JULIA D. , ROYTMAN MAYA V. , DOLAN BRIGID M. , KHAN SADIYA S. , NIZNIK CHARLOTTE M. , YEE LYNN M.
Published: January 2023

Gestational diabetes mellitus and hypertensive disorders in pregnancy are adverse pregnancy outcomes (APOs) that affect 15% of pregnancies in the United States. These APOs have long-term health implications, with greater risks of future cardiovascular and chronic disease later in life. In this manuscript, we review the importance of timely postpartum follow-up and transition to primary care after APOs for future disease prevention. We also discuss interventions to improve postpartum follow-up and long-term health after an APO. In recognizing racial and ethnic disparities in APOs and chronic disease, we review important considerations of these interventions through a health equity lens.
Nutraceuticals in the Prevention and Therapeutic Treatment of Cardiovascular and Cerebrovascular Disease
Authors: Fleenor Bradley S. , Carlini Nicholas A. , Martens Christopher R.
Published: January 2023

Purpose:

This review overviews and highlights arterial stiffening as a key physiological process and target for the prevention and/or lowering of cardio- and cerebrovascular disease (collectively CVD) risk.

Methods:

We identified nutraceutical approaches from randomized controlled trials and discussed the associated mechanisms by which these compounds lower age-related arterial stiffness. Age-related CVD are the leading cause of mortality in modernized societies. Arterial dysfunction, specifically stiffening of the large elastic arteries during midlife, is a key physiological process resulting in increased CVD risk. Current pharmaceutical approaches for lowering age-related arterial stiffness have limited efficacy, thus highlighting the need to identify novel approaches for lowering arterial stiffness and thereby CVD risk. Lifestyle interventions are a historical first-line approach to prevent and/or lower the adverse arterial stiffening effects observed with aging. Nutraceutical interventions, defined as a food or part of a food providing health benefits, are a nonpharmacological, novel lifestyle approach to lower age-associated arterial stiffness. Therefore, identifying nutraceutical approaches to lower CVD risk is clinically significant.

This review provides a basic, yet essential, understanding for emerging nutraceutical strategies for the prevention and therapeutic treatment of CVD.
Association between renal sympathetic denervation and arterial stiffness: the ASORAS study
Authors: Zeijen Victor J.M. , Feyz Lida , Kardys Isabella , Geleijnse Marcel L. , Van Mieghem Nicolas M. , Zijlstra Felix , Lafeber Melvin , Van Der Geest Rob J. , Hirsch Alexander , Daemen Joost
Published: January 2023

Objectives:

Renal sympathetic denervation (RDN) reduces blood pressure (BP). However, one out of three patients does not exhibit a significant BP response to the therapy. This study investigates the association between noninvasive vascular stiffness indices and RDN-mediated BP reduction.

Methods:

In this prospective, single-arm pilot study, patients with systolic office BP at least 140 mmHg, mean 24-h systolic ambulatory blood pressure (ABP) at least 130 mmHg and at least three prescribed antihypertensive drugs underwent radiofrequency RDN. The primary efficacy endpoint was temporal evolution of mean 24-h systolic ABP throughout 1-year post RDN (measured at baseline and 3–6–12 months). Effect modification was studied for baseline ultrasound carotid–femoral and magnetic resonance (MR) pulse wave velocity (PWV), MR aortic distensibility, cardiac MR left ventricular parameters and clinical variables. Statistical analyses were performed using linear mixed-effects models, and effect modification was assessed using interaction terms.

Results:

Thirty patients (mean age 62.5 ± 10.7 years, 50% women) with mean 24-h ABP 146.7/80.8 ± 13.7/12.0 mmHg were enrolled. Following RDN, mean 24-h systolic ABP changed with −8.4 (95% CI: −14.5 to −2.3) mmHg/year (P = 0.007). Independent effect modifiers were CF-PWV [+2.7 (0.3 to 5.1) mmHg/year change in outcome for every m/s increase in CF-PWV; P = 0.03], daytime diastolic ABP [−0.4 (−0.8 to 0.0) mmHg/year per mmHg; P = 0.03], age [+0.6 (0.2 to 1.0) mmHg/year per year of age; P = 0.006], female sex [−14.0 (−23.1 to −5.0) mmHg/year as compared with men; P = 0.003] and BMI [+1.2 (0.1 to 2.2) mmHg/year per kg/m2; P = 0.04].

Conclusion:

Higher CF-PWV at baseline was associated with a smaller reduction in systolic ABP following RDN. These findings could contribute to improve identification of RDN responders.
INVESTIGATION OF INCIDENCE AND CAUSES OF ACUTE VISION LOSS DURING ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DURING A FOUR-YEAR FOLLOW-UP
Authors: Machida Akira , Oishi Akio , Tsuiki Eiko , Maekawa Yuki , Kurihara Junko , Hirata Yuki , Machida Eriko , Kitaoka Takashi
Published: January 2023

Purpose:

To investigate the incidence, risk factors, and outcomes of patients with age-related macular degeneration who experienced acute vision loss despite periodic injections of anti–vascular endothelial growth factor treatment for 4 years.

Methods:

This retrospective cohort study included patients who were diagnosed with treatment-naive neovascular age-related macular degeneration and completed a 4-year follow-up. The incidence and risk factors for the occurrence of three or more lines of visual loss at every checkup were investigated.

Results:

The analysis included 76 eyes of 76 patients. Acute vision loss occurred in 30 eyes (39.5%) over 4 years. Lower baseline best-corrected visual acuity and disrupted ellipsoid zone were independent predictors of vision loss occurrence. Although the causes and timing of visual acuity loss varied, retinal pigment epithelium tears were observed only in the first year. Most patients (86.7%) who experienced vision loss recovered their vision to pre-loss levels at least once; however, the final best-corrected visual acuity was worse than that in the group that did not experience acute vision loss.

Conclusion:

Approximately half of the patients with age-related macular degeneration experienced acute vision loss during a 4-year follow-up, despite continuous anti–vascular endothelial growth factor treatment. Most patients recovered from vision losses temporarily; however, they experienced worse visual outcomes subsequently.
Anticoagulation and Thrombotic Events in the Multisystem Inflammatory Syndrome in Children: Experience of a Single-center Cohort and Review of the Literature
Authors: Pegoraro Francesco , Lasagni Donatella , Trapani Sandra , Mastrolia Maria V. , Simonini Gabriele , Indolfi Giuseppe , Resti Massimo
Published: January 2023

The multisystem inflammatory syndrome in children (MIS-C) is a severe clinical entity affecting the coagulative system; although thromboembolic events (TEs) are not common, most patients receive anticoagulation.

We retrospectively assessed patients below 18 years admitted with MIS-C at Meyer Children’s Hospital (Florence, Italy). Data on baseline clinical and laboratory presentation, treatment, and outcome, including differences between patients with and without thrombotic prophylaxis, were analyzed.

Thirty-two children 1 to 15 years were included. Seventeen patients (53.1%) required intensive care admission, 2 (8.7%) had obesity, 7 (30.4%) a central venous catheter, and 14 (43.8%) an impaired cardiac function. Twelve patients (37.5%) received prophylactic anticoagulation: they had more frequent cardiac involvement (91.7 vs. 50%, P=0.02) and higher ferritin levels (median 1240 vs. 501.5 ng/mL, P<0.001). No differences were found in median d-dimers between the 2 groups. Twenty-one patients (65.6%) had d-dimers >5×upper limit of normal but the indication for anticoagulation was not driven by d-dimers. No patient had hemorrhagic events and only 1 patient (3.1%) had a superficial thrombotic event (under thromboprophylaxis).

Our series and the available literature data on MIS-C and thromboembolic events suggest that TEs are a rare complication of MIS-C that is frequently associated with high d-dimer values. However, also in MIS-C, the well-established risk factors of pediatric TEs (ie, older age, central venous catheter, obesity, and cancer) should guide thromboembolic risk assessment.
Implementing a Fall Prevention Initiative in Nurse-Facilitated Annual Wellness Visits
Authors: Quinlan Sharon , Ryer Suzanne
Published: January 2023

Background:

Falls are the leading cause of injury-related death and disability in community-dwelling older adults.

Local Problem:

Evidence-based fall prevention activities in primary care, including nurse-facilitated wellness visits, have been limited. Barriers including patient engagement and adherence exist.

Method:

A quality improvement project integrating components of the Centers for Disease Control and Prevention's Stopping Elder Accidents, Deaths & Injury (STEADI) was introduced by registered nurses during older adult annual wellness visits.

Intervention:

Nurses assessed risk and implemented patient-centered fall prevention plans including follow-up.

Results:

A total of 522 patients were screened, with 21% (n = 111) having increased fall risk. Of these, 78% (n = 87) engaged in home safety, gait, strength, and balance assessments and the majority (n = 83; 95%) participated in fall prevention plans of care. At 2-week follow-up, patients' self-reported adherence was 74% for gait/strength/balance and 67% for home safety.

Conclusion:

An expanded primary care team model shows promise for promoting fall prevention behaviors.
Treatment Strategy for Condyle/Ramus Deficiency Using 3D Virtual Surgery and CAD/CAM Technologies; Total Joint Replacement or Inverted-L Osteotomy
Authors: Maeng Ji Youn , Ha Sung-Ho , Baek Seung-Hak , Choi Jin-Young
Published: January 2023

Objective:

To introduce a guideline for selecting proper surgical modalities for correction of skeletal Class II malocclusion with moderate-to-severe vertical height deficiency (VHD) of the condyle/ramus complex (CRC) using bimaxillary surgery in conjunction with total joint replacement (TJR) or inverted-L osteotomy (ILO) assisted by 3D virtual surgical planning and CAD/CAM technologies.

Cases:

Four cases of severe skeletal Class II patients with moderate-to-severe VHD of CRC were presented. They underwent bimaxillary surgery using Le Fort I osteotomy in the maxilla and TJR or ILO in the mandible, with the help of virtual surgical planning (VSP) and computer-aided design/computer-aided manufacturing (CAD/CAM)-printed surgical guides and osteosynthesis plates. Guidelines are as follows: (1) if a patient has a moderate degree of VHD and the function of the temporomandibular joint (TMJ) is normal, ILO would be preferred for vertical elongation of the ramus; (2) if a patient has congenitally small condyle or severe condylar resorption, TJR would be preferred to resolve severe VHD of CRC; and (3) when a patient has a metal allergy, foreign body reaction or anatomic limitations (ie, thin cranial base cortex for fossa fixation), ILO would be a better option than TJR.

Results:

TJR or ILO using VSP and CAD/CAM-printed surgical guides, wafers, and customized plates can provide a proper selection of the surgical plan, accurate transfer of surgical plans to actual surgical procedures, and esthetic improvement of the facial profile.

Conclusion:

This guideline based on the degree of VHD and functional aspects of CRC might help clinicians to select effective surgical modality for correction of skeletal Class II malocclusion with moderate-to-severe VHD of CRC.
Vibrio amylolyticus sp. nov. and Vibrio gelatinilyticus sp. nov., two marine bacteria isolated from surface seawater of Qingdao
Authors: Zhang Pingping , Wang Xiaolei , Liu Ronghua , Zhu Xiaoyu , Zhao Wenbin , Zhang Xiao-Hua
Published: January 2023

Two Gram-stain-negative, oxidase-positive, facultative anaerobic and rod-shaped motile bacteria, designated strains ZSDZ34 and ZSDE26, were isolated from offshore surface seawater collected near Qingdao. Phylogenetic analysis based on 16S rRNA gene sequences placed ZSDE26T and ZSDZ34T within the genus

Vibrio

, family

Vibrionaceae

, class

Gammaproteobacteria

. Strain ZSDE26T was most closely related to

Vibrio gallaecicus

VB 8.9T with 97.3 % sequence similarity, whereas ZSDZ34T was most closely related to

Vibrio aestuarianus

subsp.

cardii

DSM 109723T with 97.8 % sequence similarity. Strain ZSDE26T grew with 1–5 % (w/v) NaCl (optimum, 4 %), at 16–28 °C (optimum, 28 °C) and at pH 6.0–9.0 (optimum, pH 7.0). Growth of strain ZSDZ34T occurred with 1–6 % (w/v) NaCl (optimum, 3 %), at 16–37 °C (optimum, 28 °C) and at pH 6.0–9.0 (optimum, pH 7.0). Both strains shared the same major fatty acid components (more than 10 % of total fatty acids) of summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c), summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c) and C16 : 0. Additionally, strain ZSDZ34T contained a higher proportion of iso-C16 : 0. The DNA G+C contents of strains ZSDE26T and ZSDZ34T were 42.8 and 44.5 mol%, respectively. On the basis of the results of polyphasic analysis, ZSDE26T and ZSDZ34T are considered to represent novel species within the genus

Vibrio

, for which the names Vibrio amylolyticus sp. nov. (type strain, ZSDE26T=KCTC 82890T=MCCC 1K06290T) and Vibrio gelatinilyticus sp. nov. (type strain, ZSDZ34T=KCTC 82888T=MCCC 1K06292T) are proposed, respectively.
Robust single membrane protein tweezers
Authors: Kim Seoyoon , Lee Daehyo , Wijesinghe W.C. Bhashini , Min Duyoung
Published: January 2023

Single-molecule tweezers, such as magnetic tweezers, are powerful mechanical manipulation tools that can probe nm-scale structural changes in a single membrane protein under force. However, the weak molecular tethers used in the tweezers limit a long time, repetitive mechanical manipulation because of their force-induced bond breakage. Here, using the metal-free click chemistry of dibenzocyclooctyne (DBCO) cycloaddition and the rapid, strong binding of traptavidin to dual biotins (2xbiotin), we developed robust single-molecule tweezers that can perform thousands of force applications on a single membrane protein. By applying up to 50 pN for each cycle, which is sufficiently high for most biological processes, we were able to observe repetitive forced unfolding for a designer membrane protein up to approximately 1000 times on average. Monte Carlo simulations showed that the average error of the unfolding kinetic values rapidly decays to 1.8% at 200-time pulling, indicating that our method can quickly produce reliable statistics. The approach established here is also applicable to highly polar DNA molecules, permitting the nanomechanical manipulation of diverse biomolecular systems.
Hippocampal area CA2 controls seizure dynamics, interictal EEG abnormalities and social comorbidity in mouse models of temporal lobe epilepsy
Authors: Lisgaras Christos Panagiotis , Oliva Azahara , Mckenzie Sam , LaFrancois John , Siegelbaum Steven A. , Scharman Helen E.
Published: January 2023

Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures, abnormal activity between seizures, and impaired behavior. CA2 pyramidal neurons (PNs) are potentially important because inhibiting them with a chemogenetic approach reduces seizure frequency in a mouse model of TLE. However, whether seizures could be stopped by timing inhibition just as a seizure begins is unclear. Furthermore, whether inhibition would reduce the cortical and motor manifestations of seizures are not clear. Finally, whether interictal EEG abnormalities and TLE comorbidities would be improved are unknown. Therefore, real-time optogenetic silencing of CA2 PNs during seizures, interictal activity and behavior were studied in 2 mouse models of TLE. CA2 silencing significantly reduced seizure duration and time spent in convulsive behavior. Interictal spikes and high frequency oscillations were significantly reduced, and social behavior was improved. Therefore, brief focal silencing of CA2 PNs reduces seizures, their propagation, and convulsive manifestations, improves interictal EEG, and ameliorates social comorbidities.

HIGHLIGHTS

Real-time CA2 silencing at the onset of seizures reduces seizure duration

When CA2 silencing reduces seizure activity in hippocampus it also reduces cortical seizure activity and convulsive manifestations of seizures

Interictal spikes and high frequency oscillations are reduced by real-time CA2 silencing

Real-time CA2 silencing of high frequency oscillations (>250Hz) rescues social memory deficits of chronic epileptic mice