bluuebunny/crossref_metadata_2025 huggingface dataset:
A surprising abundance of massive quiescent galaxies at 3 <z< 5 in the first data fromJWSTCEERS
Authors: Carnall A C , McLeod D J , McLure R J , Dunlop J S , Begley R , Cullen F , Donnan C T , Hamadouche M L , Jewell S M , Jones E W , Pollock C L , Wild V
Published: February 2023

We report a robust sample of 10 massive quiescent galaxies at redshift, z > 3, selected using the first data from the JWST Cosmic Evolution Early Release Science programme. Three of these galaxies are at 4 < z < 5, constituting the best evidence to date for quiescent galaxies significantly before z = 4. These extreme galaxies have stellar masses in the range log10(M*/M⊙) = 10.1–11.1, and formed the bulk of their mass around z ≃ 10, with two objects having star formation histories that suggest they had already reached log10(M*/M⊙) > 10 by z ≳ 8. We report number densities for our sample, demonstrating that, based on the small area of JWST imaging so far available, previous work appears to have underestimated the number of quiescent galaxies at 3 < z < 4 by a factor of 3–5, due to a lack of ultra-deep imaging data at $\lambda \gt 2\, \mu$m. This result deepens the existing tension between observations and theoretical models, which already struggle to reproduce previous estimates of z > 3 quiescent galaxy number densities. Upcoming wider-area JWST imaging surveys will provide larger samples of such galaxies and more robust number densities, as well as providing opportunities to search for quiescent galaxies at z > 5. The galaxies we report are excellent potential targets for JWST NIRSpec spectroscopy, which will be required to understand in detail their physical properties, providing deeper insights into the processes responsible for forming massive galaxies and quenching star formation during the first billion years.
Proto-neutron star convection and the neutrino-driven wind: implications for the r-process
Authors: Nevins Brian , Roberts Luke F
Published: February 2023

The neutrino-driven wind from proto-neutron stars is a proposed site for r-process nucleosynthesis, although most previous work has found that a wind heated only by neutrinos cannot produce the third r-process peak. However, several groups have noted that introducing a secondary heating source within the wind can change the hydrodynamic conditions sufficiently for a strong r-process to proceed. One possible secondary heating source is gravito-acoustic waves, generated by convection inside the proto-neutron star. As these waves propagate into the wind, they can both accelerate the wind and shock and deposit energy into the wind. Additionally, the acceleration of the wind by these waves can reduce the total number of neutrino captures and thereby reduce the final electron fraction of the wind. In neutron rich conditions, all of these effects can make conditions more favourable for r-process nucleosynthesis. Here, we present a systematic investigation of the impact of these convection-generated gravito-acoustic waves within the wind on potential nucleosynthesis. We find that wave effects in the wind can generate conditions favourable for a strong r-process, even when the energy flux in the waves is a factor of 10−4 smaller than the total neutrino energy flux and the wind is marginally neutron rich. Nevertheless, this depends strongly on the radius at which the waves become non-linear and form shocks. We also find that both entropy production after shock formation and the acceleration of the wind due to stresses produced by the waves prior to shock formation impact the structure and nucleosynthesis of these winds.
Deciphering the Genetic Basis of Silkworm Cocoon Colors Provides New Insights into Biological Coloration and Phenotypic Diversification
Authors: Lu Yaru , Luo Jiangwen , An Erxia , Lu Bo , Wei Yinqiu , Chen Xiang , Lu Kunpeng , Liang Shubo , Hu Hai , Han Minjin , He Songzhen , Shen Jianghong , Guo Dongyang , Bu Nvping , Yang Ling , Xu Wenya , Lu Cheng , Xiang Zhonghuai , Tong Xiaoling , Dai Fangyin
Published: January 2023

The genetic basis of phenotypic variation is a long-standing concern of evolutionary biology. Coloration has proven to be a visual, easily quantifiable, and highly tractable system for genetic analysis and is an ever-evolving focus of biological research. Compared with the homogenized brown-yellow cocoons of wild silkworms, the cocoons of domestic silkworms are spectacularly diverse in color, such as white, green, and yellow-red; this provides an outstanding model for exploring the phenotypic diversification and biological coloration. Herein, the molecular mechanism underlying silkworm green cocoon formation was investigated, which was not fully understood. We demonstrated that five of the seven members of a sugar transporter gene cluster were specifically duplicated in the Bombycidae and evolved new spatial expression patterns predominantly expressed in silk glands, accompanying complementary temporal expression; they synergistically facilitate the uptake of flavonoids, thus determining the green cocoon. Subsequently, polymorphic cocoon coloring landscape involving multiple loci and the evolution of cocoon color from wild to domestic silkworms were analyzed based on the pan-genome sequencing data. It was found that cocoon coloration involved epistatic interaction between loci; all the identified cocoon color-related loci existed in wild silkworms; the genetic segregation, recombination, and variation of these loci shaped the multicolored cocoons of domestic silkworms. This study revealed a new mechanism for flavonoids-based biological coloration that highlights the crucial role of gene duplication followed by functional diversification in acquiring new genetic functions; furthermore, the results in this work provide insight into phenotypic innovation during domestication.
Plasticity and Stereotypic Rewiring of the Transcriptome Upon Bacterial Evolution of Antibiotic Resistance
Authors: Grézal Gábor , Spohn Réka , Méhi Orsolya , Dunai Anett , Lázár Viktória , Bálint Balázs , Nagy István , Pál Csaba , Papp Balázs
Published: January 2023

Bacterial evolution of antibiotic resistance frequently has deleterious side effects on microbial growth, virulence, and susceptibility to other antimicrobial agents. However, it is unclear how these trade-offs could be utilized for manipulating antibiotic resistance in the clinic, not least because the underlying molecular mechanisms are poorly understood. Using laboratory evolution, we demonstrate that clinically relevant resistance mutations in Escherichia coli constitutively rewire a large fraction of the transcriptome in a repeatable and stereotypic manner. Strikingly, lineages adapted to functionally distinct antibiotics and having no resistance mutations in common show a wide range of parallel gene expression changes that alter oxidative stress response, iron homeostasis, and the composition of the bacterial outer membrane and cell surface. These common physiological alterations are associated with changes in cell morphology and enhanced sensitivity to antimicrobial peptides. Finally, the constitutive transcriptomic changes induced by resistance mutations are largely distinct from those induced by antibiotic stresses in the wild type. This indicates a limited role for genetic assimilation of the induced antibiotic stress response during resistance evolution. Our work suggests that diverse resistance mutations converge on similar global transcriptomic states that shape genetic susceptibility to antimicrobial compounds.
The impact of nucleosome structure on CRISPR/Cas9 fidelity
Authors: Handelmann Christopher R , Tsompana Maria , Samudrala Ram , Buck Michael J
Published: February 2023

The clustered regularly interspaced short palindromic repeats (CRISPR) Cas system is a powerful tool that has the potential to become a therapeutic gene editor in the near future. Cas9 is the best studied CRISPR system and has been shown to have problems that restrict its use in therapeutic applications. Chromatin structure is a known impactor of Cas9 targeting and there is a gap in knowledge on Cas9’s efficacy when targeting such locations. To quantify at a single base pair resolution how chromatin inhibits on-target gene editing relative to off-target editing of exposed mismatching targets, we developed the gene editor mismatch nucleosome inhibition assay (GEMiNI-seq). GEMiNI-seq utilizes a library of nucleosome sequences to examine all target locations throughout nucleosomes in a single assay. The results from GEMiNI-seq revealed that the location of the protospacer-adjacent motif (PAM) sequence on the nucleosome edge drives the ability for Cas9 to access its target sequence. In addition, Cas9 had a higher affinity for exposed mismatched targets than on-target sequences within a nucleosome. Overall, our results show how chromatin structure impacts the fidelity of Cas9 to potential targets and highlight how targeting sequences with exposed PAMs could limit off-target gene editing, with such considerations improving Cas9 efficacy and resolving current limitations.
eIF4A1-dependent mRNAs employ purine-rich 5’UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation
Authors: Schmidt Tobias , Dabrowska Adrianna , Waldron Joseph A , Hodge Kelly , Koulouras Grigorios , Gabrielsen Mads , Munro June , Tack David C , Harris Gemma , McGhee Ewan , Scott David , Carlin Leo M , Huang Danny , Le Quesne John , Zanivan Sara , Wilczynska Ania , Bushell Martin
Published: February 2023

Altered eIF4A1 activity promotes translation of highly structured, eIF4A1-dependent oncogene mRNAs at root of oncogenic translational programmes. It remains unclear how these mRNAs recruit and activate eIF4A1 unwinding specifically to facilitate their preferential translation. Here, we show that single-stranded RNA sequence motifs specifically activate eIF4A1 unwinding allowing local RNA structural rearrangement and translation of eIF4A1-dependent mRNAs in cells. Our data demonstrate that eIF4A1-dependent mRNAs contain AG-rich motifs within their 5’UTR which specifically activate eIF4A1 unwinding of local RNA structure to facilitate translation. This mode of eIF4A1 regulation is used by mRNAs encoding components of mTORC-signalling and cell cycle progression, and renders these mRNAs particularly sensitive to eIF4A1-inhibition. Mechanistically, we show that binding of eIF4A1 to AG-rich sequences leads to multimerization of eIF4A1 with eIF4A1 subunits performing distinct enzymatic activities. Our structural data suggest that RNA-binding of multimeric eIF4A1 induces conformational changes in the RNA resulting in an optimal positioning of eIF4A1 proximal to the RNA duplex enabling efficient unwinding. Our data proposes a model in which AG-motifs in the 5’UTR of eIF4A1-dependent mRNAs specifically activate eIF4A1, enabling assembly of the helicase-competent multimeric eIF4A1 complex, and positioning these complexes proximal to stable localised RNA structure allowing ribosomal subunit scanning.
Clostridioides difficileBinary Toxin Binding Component Increases Virulence in a Hamster Model
Authors: Simpson Morgan , Bilverstone Terry , Leslie Jhansi , Donlan Alexandra , Uddin Md Jashim , Petri William A , Marin Natasha , Kuehne Sarah , Minton Nigel P , Petri William A
Published: January 2023

Background

Clostridioides difficile is the leading cause of hospital-acquired gastrointestinal infection, in part due to the existence of binary toxin (CDT)-expressing hypervirulent strains. Although the effects of the CDT holotoxin on disease pathogenesis have been previously studied, we sought to investigate the role of the individual components of CDT during in vivo infection.

Methods

To determine the contribution of the separate components of CDT during infection, we developed strains of C difficile expressing either CDTa or CDTb individually. We then infected both mice and hamsters with these novel mutant strains and monitored them for development of severe illness.

Results

Although expression of CDTb without CDTa did not induce significant disease in a mouse model of C difficile infection, we found that complementation of a CDT-deficient C difficile strain with CDTb alone restored virulence in a hamster model of C difficile infection.

Conclusions

Overall, this study demonstrates that the binding component of C difficile binary toxin, CDTb, contributes to virulence in a hamster model of infection.
Factors Associated With Long COVID Symptoms in an Online Cohort Study
Authors: Durstenfeld Matthew S , Peluso Michael J , Peyser Noah D , Lin Feng , Knight Sara J , Djibo Audrey , Khatib Rasha , Kitzman Heather , O’Brien Emily , Williams Natasha , Isasi Carmen , Kornak John , Carton Thomas W , Olgin Jeffrey E , Pletcher Mark J , Marcus Gregory M , Beatty Alexis L
Published: February 2023

Background

Few prospective studies of Long COVID risk factors have been conducted. The purpose of this study was to determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are associated with Long COVID.

Methods

In March 26, 2020, the COVID-19 Citizen Science study, an online cohort study, began enrolling participants with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection. Adult participants who reported a positive SARS-CoV-2 test result before April 4, 2022 were surveyed for Long COVID symptoms. The primary outcome was at least 1 prevalent Long COVID symptom greater than 1 month after acute infection. Exposures of interest included age, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, variant wave, number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, and exercise.

Results

Of 13 305 participants who reported a SARS-CoV-2 positive test, 1480 (11.1%) responded. Respondents’ mean age was 53 and 1017 (69%) were female. Four hundred seventy-six (32.2%) participants reported Long COVID symptoms at a median 360 days after infection. In multivariable models, number of acute symptoms (odds ratio [OR], 1.30 per symptom; 95% confidence interval [CI], 1.20–1.40), lower socioeconomic status/financial insecurity (OR, 1.62; 95% CI, 1.02–2.63), preinfection depression (OR, 1.08; 95% CI, 1.01–1.16), and earlier variants (OR = 0.37 for Omicron compared with ancestral strain; 95% CI, 0.15–0.90) were associated with Long COVID symptoms.

Conclusions

Variant wave, severity of acute infection, lower socioeconomic status, and pre-existing depression are associated with Long COVID symptoms.
The Association Between Medication Use in Older Women with Early-Stage Operable Primary Breast Cancer and Decision Regarding Primary Treatment
Authors: Tse Natalie , Parks Ruth M , Holmes Holly M , Cheung Kwok-Leung
Published: January 2023

Background

Polypharmacy is one factor contributing to increased mortality, hospitalization, and adverse drug reactions in older adults. The aim of this study was to measure the prevalence of polypharmacy in a cohort of older women with early-stage operable primary breast cancer and the relationship of polypharmacy to primary treatment decision and functional status.

Methods

A total of 139 patients with a new diagnosis of early-stage operable primary breast cancer proven histologically were recruited as part of a prospective study. The average age was 77 years. Assessment using a cancer-specific Comprehensive Geriatric Assessment (CGA) tool was conducted within 6 weeks of diagnosis of breast cancer. Association was determined between number of medications and treatment decision and physical status as measured by the CGA outcomes. Additional analysis was performed to determine the associations above with polypharmacy defined by ≥5 daily medications, and if cardiovascular-related diseases have a role in the treatment decision.

Results

Polypharmacy was present in 48% of patients (n = 139). CGA determined that polypharmacy was associated with greater comorbidity (P < .001), reduced physical status rated by physicians (P = .009) and patients (P = .019), and reduced ability to perform activities of instrumental ADLs (P = .008). Similar findings were present in the analysis of cardiovascular-related diseases.

Conclusions

This work suggests that patients with polypharmacy are more likely to be frail. The number of medications could help us screen patients who should go on to receive full CGA.
Gradability and Comparison in Kannada
Authors: Herur Sindhu , Amritavalli R.
Published: January 2023

Gradable nouns participate in comparison without the need for a quantifier to project a degree head. Case, genitive, or dative (and of in English) can function to project a degree head; bare property concept nouns in the dative subject construction are not gradable, but their dative/genitive-marked counterparts are. Thus, one source for a category of adjectives from a universal two-category lexical base (N, V) is by the absorption of N into a degree case-head. Taking also have as be which absorbs the dative case, the stability of morphological case in Dravidian explains the lack of have and the paucity of adjectives, and thus, the inevitability of the dative subject construction.
State-Building in Historical Political Economy
Authors: Garfias Francisco , Sellars Emily A.
Published: January 2023

Under what conditions do strong states under a centralized political authority emerge? This chapter presents a theoretical framework that summarizes and synthesizes insights from recent research in historical political economy on state building. The chapter examines the decision of a central authority who weighs the costs and benefits of state building by taxing the population to defend against a threat. The analysis illustrates prominent arguments in the literature, including the role of external conflict, military technology, nontax revenue, societal wealth, the technology of taxation, and fiscal legibility in state building. The chapter then considers how powerful local elites, whose interests may not align with the central authority, can shift a ruler’s willingness and ability to centralize power, drawing a connection with the literatures on intra-elite conflict and limited government. Finally, the chapter expands the framework to incorporate non-elite citizens, who can pressure elites and central authorities through the threat of rebellion from below, to discuss the role of elite-mass relations in state building.
Using Zircons to Disentangle Back-Veining and Hybridization of Diorite Dykes: an Example From the Gangdese Arc, Tibet
Authors: Weinberg Roberto F , Moyen Jean-François , Yi Jian-Kang , Zhu Di-Cheng , Nebel Oliver , Chen Shaorong , Wang Qing
Published: February 2023

Thermo-chemical modeling and chemical data suggest that the genesis of arc melts commonly involves re-melting of older intrusions, triggered by the injection of mantle-derived melts, followed by magma mixing. Remelting and mixing may lead to complex zircon populations, which can be used to gain insights into the conditions of mixing. This paper investigates a case where such processes can be studied through the compositional and thermal record provided by zircons preserved in a diorite dyke swarm that remelted host rock tonalites in the Gangdese Batholith in Tibet. Autocrystic zircons from the diorite yield consistent ages of 46 to 47 Ma even though they can be altered, having highly enriched trace elements, reaching ~1 wt % in Fe, Ca, Y, U, Th, and anomalously high values of LREE and Ti. Granitic magmas derived from the tonalite, back-veined the dykes and mixed with the dioritic mush, transferring small quantities of 77–79 Ma zircon xenocrysts. The xenocrysts are euhedral with little evidence for resorption, indicating that they were apparently stable during the process of tonalite anatexis and transfer to the diorite magma. This requires that: (i) tonalite melting occurred at low temperatures with minimal zircon dissolution, and (ii) the diorite either cooled rapidly before significant resorption of the grains or was already saturated in zircon when mixing occurred. Zircon saturation temperatures of the diorite are relatively low, indicating that xenocrystic zircons were transferred to a highly crystalline dioritic mush. This requires either liquefaction by injection of the back-veining felsic magma to allow for mixing, or pervasive throughflow of the diorite mush by the felsic magma leaving behind zircon xenocrysts. The findings suggest that the dykes triggered low-T, water-fluxed melting of the host tonalite and that these anatectic melts invaded the diorite mush initially through the interstices leading to mixing. This may have caused the breakdown of the crystalline framework leading to liquefaction and renewed magma flow. Dyking and assimilation of wall-rock through back-veining as recorded in these rocks could be common in transcrustal arcs. However, this process could be hidden due to a combination of the similarity in the isotopic and chemical nature of arc rocks and resorption of zircon xenocrysts during mixing. This process may explain some complex chemistry of arc magmatic rocks and their minerals that are not easily explained by endmember models, such as pure re-melting of older arc rocks or fractional crystallization of mantle-derived melts.
Stellate ganglion block for non-pain indications: a scoping review
Authors: Feigin Guy , Velasco Figueroa Sofia , Englesakis Marina F , D’Souza Rohan , Hoydonckx Yasmine , Bhatia Anuj
Published: February 2023

Introduction

Stellate ganglion block (SGB) is performed to relieve head, face, neck, or upper limb pain, and several non-pain indications for performing this block have emerged over the years. To date, there has been no attempt to synthesize evidence on SGB for treating non-pain indications. This scoping review presents a summary of the efficacy and adverse effects of SGB when performed for 6 non-pain indications.

Methods

This scoping review was accomplished through the use of Arksey and O’Malley framework. A literature search was conducted for relevant articles in medical databases to identify publications on SGB and specified study types. Two reviewers independently assessed the risk of bias for randomized controlled trials, nonrandomized comparative studies, and case series. Results were summarized and recommendations were made on the basis of the strength of the available evidence according to the US Preventative Services Task Force grading system.

Results

Twenty-four studies (19 randomized controlled trials and 5 nonrandomized studies) were included in this review. On the basis of the evidence, SGB is recommended for obtunding cardiovascular sympathetic stimulation, improving perfusion in limbs, and alleviating menopausal symptoms with a Grade B or C recommendation and a moderate-to-low level of certainty. There was insufficient evidence to recommend SGB for the other indications.

Conclusions

SGB can be considered for obtunding cardiovascular sympathetic stimulation and stress response, reducing vascular tone to improve vascular insufficiency in the limbs and perioperative hemodynamic stability, and alleviating hot flashes in menopause, in conditions refractory to conventional medical management.
Survey Attention and Self-Reported Political Behavior
Authors: Alvarez R Michael , Li Yimeng
Published: February 2023

Survey research methodology is evolving rapidly, as new technologies provide new opportunities. One of the areas of innovation regards the development of online interview best practices and the advancement of methods that allow researchers to measure the attention that respondents are devoting to the survey task. Reliable measurement of respondent attention can yield important information about the quality of the survey response. In this article, we take advantage of an innovative survey we conducted in 2018, in which we directly connect survey responses to administrative data, allowing us to assess the association between survey attention and response quality. We show that attentive survey respondents are more likely to provide accurate survey responses regarding a number of behaviors and attributes that we can validate with our administrative data. We discuss the best strategy to deal with inattentive respondents in surveys in light of our results.
PHILIP MORRIS PRODUCTS, SA v RAI STRATEGIC HOLDINGS, INC
Authors:   Patents Court
Published: February 2023

H1 Patents — European Patents — Tobacco products — “Heat Not Burn” technology — Validity — Infringement — Construction — “For use with” — The role of preferred embodiments — Person skilled in the art — Common general knowledge — Added matter — Pleadings — Obviousness — Arbitrary choices — Lack of technical contribution — Infringement — Exclusive licences
In vitro high glucose increases apoptosis, decreases nerve outgrowth, and promotes survival of sympathetic pelvic neurons
Authors: Pallas Wrenn D , Pak Elena S , Hannan Johanna L
Published: February 2023

Background

Diabetes mellitus (DM) is a common cause of erectile dysfunction (ED), yet the molecular basis of DM neurogenic ED remains unknown.

Aim

In this study we examined the impact of high glucose on survival and growth of primary cultured pelvic neurons in a rat model and assessed whether coculturing with healthy Schwann cells (SCs) can rescue pelvic neuron growth in patients with DM.

Methods

Major pelvic ganglia (MPGs) from adult male Sprague Dawley rats (n = 8) were dissociated and plated on coverslips. Neurons were exposed to high glucose (45 mM) for 24 or 48 hours and compared to time-matched controls (25 mM). Neurons were stained for neuron-specific beta-tubulin, neuronal nitric oxide synthase, vesicular acetylcholine transferase, tyrosine hydroxylase, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling) assay. Schwann cells were dissociated from MPGs of healthy male Sprague Dawley rats (n = 4) and grown to confluence. Additional Sprague Dawley rats were made diabetic with streptozotocin (50 mg/kg, n = 4), and 5 weeks later MPGs were collected from these rats, dissociated, and cocultured on healthy SCs. Neurons and SCs were stained with beta-tubulin and S100.

Outcomes

Length, branching, and survival of nitrergic, parasympathetic, and sympathetic neurons was assessed in neurons exposed to normal or high glucose concentrations, and neuron length was measured in neuron-SC coculture.

Results

The total number of neurons and the length and number of branches were significantly decreased after 24 and 48 hours of high glucose (P < .05). The percentage of nitrergic neurons decreased 10% after 24 hours and 50% after 48 hours of high glucose (P < .05). After 24 hours of high glucose, cholinergic-positive neurons were unchanged; however, these neurons decreased 30% after 48 hours (P < .05). The proportion of sympathetic neurons increased 25% after 48 hours of high glucose (P < .05). At both timepoints, there was a 2-fold increase in the total apoptotic neurons with high glucose (P < .05). Neurite outgrowth recovered to control lengths after coculture of diabetic neurons with healthy SCs (P < .05).

Clinical Translation

Glucose can be used as a tool to investigate the direct effects of DM on neuritogenesis. Our data suggest that an effective treatment for DM ED protects and repairs the penile neuronal supply.

Strengths and Limitations

Exposing MPG neurons to high glucose offers a quick and, inexpensive proxy for DM-related conditions. A limitation of our study is that our model reflects type 1 DM, whereas clinically, most diabetic ED patients have type 2 DM.

Conclusion

Culturing pelvic neurons in high glucose can be used as a tool to elucidate how to protect proerectile neurons from cell death and may lead to new therapeutic strategies for diabetic men suffering from ED.
Sleep spindles in the healthy brain from birth through 18 years
Authors: Kwon Hunki , Walsh Katherine G , Berja Erin D , Manoach Dara S , Eden Uri T , Kramer Mark A , Chu Catherine J
Published: January 2023

Study Objective

Sleep spindles are present from birth and reflect cognitive functions across the lifespan, but normative values for this cognitive biomarker across development are lacking. This study aims to establish normative spindle features over development.

Methods

All available normal 19-channel electroencephalograms from developmentally normal children between February 2002 and June 2021 in the MGH EEG lab were analyzed. Approximately, 20 000 spindles were hand-marked to train and validate an automated spindle detector across ages. Normative values for spindle rate, duration, frequency, refractory period, and interhemispheric lag are provided for each channel and each age.

Results

Sleep EEGs from 567 developmentally normal children (range 0 days to 18 years) were included. The detector had excellent performance (F1 = 0.47). Maximal spindle activity is seen over central regions during infancy and adolescence and frontopolar regions during childhood. Spindle rate and duration increase nonlinearly, with the most rapid changes during the first 4 months of life and between ages 3 and 14 years. Peak spindle frequency follows a U-shaped curve and discrete frontal slow and central fast spindles are evident by 18 months. Spindle refractory periods decrease between ages 1 and 14 years while interhemispheric asynchrony decreases over the first 3 months of life and between ages 1 and 14 years.

Conclusions

These data provide age- and region-specific normative values for sleep spindles across development, where measures that deviate from these values can be considered pathological. As spindles provide a noninvasive biomarker for cognitive function across the lifespan, these normative measures can accelerate the discovery and diagnosis in neurodevelopmental disorders.
Managing and preventing cross-border disputes arising with the increasingly popular use of succession substitutes
Authors: Talpis Jeffrey
Published: February 2023

As the world becomes increasingly interconnected, many people are faced with increasing challenges in the planning and execution of wealth-transfer strategies upon death when they have property in different countries. At the same time, the rising popularity of succession substitutes or, as they are called in the common law world, will substitutes or non-probate devices that transfer property at death otherwise than by succession, is increasingly posing challenges for cross-border legal disputes, particularly in the absence of uniform choice of law rules relating to succession substitutes. In this article, Professor Jeffrey Talpis reviews the existing approaches for managing and preventing cross-border disputes involving, for example, the use by parties in civil law jurisdictions of common law non-probate devices, such as acquisitions in joint tenancy, pay-on-death or transfer-on-death accounts, and revocable inter vivos trusts. The author first defines and classifies succession substitutes used in domestic laws, then examines different approaches for managing cross-border disputes involving these devices in civil law and common law jurisdictions. While the author continues to promote the adoption of an international instrument to provide uniform solutions to resolve cross-border disputes arising from the use of succession substitutes, he proposes certain suggestions that, in the interim, could assist prevention of such conflicts of law.
Ten Lessons Learned in the Implementation of Mobile, Community-Based Interprofessional Clinics
Authors: Sewell Jeanna , Watts Sarah Owens , Frugé Andrew Dandridge , Ellison Kathy Jo , Helms Kristen , Dubois Eva Jean , Myers Emily W.
Published: February 2023

Incorporation of interprofessional activities within health profession programs is critical to prepare students for practice. Faculty at our institution saw a need to incorporate interprofessional education in the nursing, pharmacy, social work, and dietetics program curricula. We collaborated with a medical school in the area to develop a mobile, community-based interprofessional clinic to deliver care and education and address the needs of older adults while also providing unique, meaningful learning opportunities for students. We describe several lessons learned from our experience of developing and implementing this interprofessional clinic.
Impact of the exposome on food allergy development
Authors: Moran Timothy P.
Published: February 2023

Purpose of review

The increasing global prevalence of food allergy indicates that environmental exposures are likely contributing to food allergy development. This review summarizes recent studies on how specific factors within the external exposome may impact the development of food allergy.

Recent findings

There is strong evidence that nonoral exposure to food allergens within the living environment is a risk factor for food sensitization and food allergy. The role of air pollution in food allergy development remains unclear, as cohort studies have not found consistent relationships between air pollutant exposure and food sensitization. Early-life microbial exposures linked to a rural lifestyle are likely protective against food allergy development, possibly through alteration of the infant microbiome. In contrast, factors associated with urbanization and decreased exposure to microbes may contribute to food allergy development. Recent studies on the role of residential greenness in food allergy development suggest either no relationship or a possible increased risk for food allergy.

The external exposome comprises a number of exposures that can modify food allergy risk. Improved understanding of how complex environmental exposures interact with genetic factors will be necessary for developing effective interventions aimed at preventing food allergy development in children.
Environment and the development of severe asthma in inner city population
Authors: Lee Julia X. , Phipatanakul Wanda , Gaffin Jonathan M.
Published: February 2023

Purpose of review

Higher asthma prevalence and morbidity are seen in inner-city areas, disproportionately affecting low-income families living in substandard housing. Children within these families experience more frequent asthma exacerbations, acute care and emergency department visits, and hospitalizations, thus characterizing severe asthma. In this review, we assess recent published literature focused on indoor and outdoor exposures that contribute to the development and morbidity of asthma.

Recent findings

Many urban environmental exposures contribute to asthma burden, including tobacco/e-cigarette smoke, pest allergens, molds, and possibly synthetic chemicals such as phthalates and bisphenol A, radon, and volatile organic compounds. Individuals living in inner-city areas also experience higher levels of air pollutants and ambient heat, further perpetuating asthma incidence and severity.

This article summarizes the latest advances and provides direction for future research on risk factors, interventions, and public policy to help alleviate the burden of asthma due to urban environment exposures.
Competencies for the Use of Artificial Intelligence–Based Tools by Health Care Professionals
Authors: Russell Regina G. , Lovett Novak Laurie , Patel Mehool , Garvey Kim V. , Craig Kelly Jean Thomas , Jackson Gretchen P. , Moore Don , Miller Bonnie M.
Published: February 2023

Purpose

The expanded use of clinical tools that incorporate artificial intelligence (AI) methods has generated calls for specific competencies for effective and ethical use. This qualitative study used expert interviews to define AI-related clinical competencies for health care professionals.

Method

In 2021, a multidisciplinary team interviewed 15 experts in the use of AI-based tools in health care settings about the clinical competencies health care professionals need to work effectively with such tools. Transcripts of the semistructured interviews were coded and thematically analyzed. Draft competency statements were developed and provided to the experts for feedback. The competencies were finalized using a consensus process across the research team.

Results

Six competency domain statements and 25 subcompetencies were formulated from the thematic analysis. The competency domain statements are: (1) basic knowledge of AI: explain what AI is and describe its health care applications; (2) social and ethical implications of AI: explain how social, economic, and political systems influence AI-based tools and how these relationships impact justice, equity, and ethics; (3) AI-enhanced clinical encounters: carry out AI-enhanced clinical encounters that integrate diverse sources of information in creating patient-centered care plans; (4) evidence-based evaluation of AI-based tools: evaluate the quality, accuracy, safety, contextual appropriateness, and biases of AI-based tools and their underlying data sets in providing care to patients and populations; (5) workflow analysis for AI-based tools: analyze and adapt to changes in teams, roles, responsibilities, and workflows resulting from implementation of AI-based tools; and (6) practice-based learning and improvement regarding AI-based tools: participate in continuing professional development and practice-based improvement activities related to use of AI tools in health care.

Conclusions

The 6 clinical competencies identified can be used to guide future teaching and learning programs to maximize the potential benefits of AI-based tools and diminish potential harms.
Doing Our Best in a Broken System: The Urgent Need for Expansion of Medication for Opioid Use Disorder Treatments in the United States
Authors: Cohen Shawn , Tilley Jess , Yocheved Avi , Sue Kimberly L.
Published: January 2023

In reply:

In this commentary, we respond to Dr Vogel and Dr Dürstelar's letter to our original piece “A Plea From People Who Use Drugs to Clinicians: New Ways to Initiate Buprenorphine Are Urgently Needed in the Fentanyl Era” published in this journal in July to August 2022. We agree with much of their comment on buprenorphine initiation and point to the need for rapid expansion of medication for opioid use disorder (OUD) treatments here in the United States. It is critical to understand the context of current buprenorphine and methadone access. We point out how the treatment of OUD with agonist therapy remains limited to methadone or buprenorphine despite an increasingly toxic drug supply within our particular legal and regulatory environment and call for urgent research and pilot programs to trial additional agonist therapies for those with opioid OUD as well as regulatory changes to increase access to both methadone and buprenorphine.
Modified Thoracolumbar Interfascial Plane Block Versus Erector Spinae Plane Block in Patients Undergoing Spine Surgeries: A Randomized Controlled Trial
Authors: Kumar Amarjeet , Sinha Chandni , Kumar Ajeet , Kumari Poonam , Kumar Abhyuday , Agrawal Prabhat , Vamshi Chethan
Published: February 2023

Background:

Lumbar spine surgery is associated with significant postoperative pain. Interfascial plane blocks, such as erector spinae plane (ESP) and thoracolumbar interfascial plane (TLIP) blocks, can play a significant role in multimodal analgesic regimens.

Methods:

Sixty patients aged 18 to 60 years undergoing elective single or double-level lumbar discectomy or primary lumbar laminoplasty were recruited into this randomized double‑blind study. All patients received general anesthesia and were randomly allocated to either modified TLIP (mTLIP) block (group M) or ESP block (group E). Postoperative and intraoperative fentanyl consumption, and postoperative pain scores, were recorded.

Results:

Total 48 h postoperative fentanyl consumption was higher in Group M (189.66±141.11 µg) than in Group E (124.16±80.83 µg; P=0.031). In the first 24 postoperative hours, fentanyl consumption was higher in Group M (150.3±120.9 µg) than in group E (89.9±65.3 µg; P=0.01) but was similar between groups in postoperative hours 24to 48 (39.0±20.2 µg versus 34.7±17.1 µg in group M and group E, respectively; P=0.37). Additional intraoperative fentanyl requirement was 57.66±21.76 µg in group M compared with 40.33±21.89 µg in group E (P<0.01). Postoperative pain scores were higher in group M than in group E at 1, 2, 4, 6, 12, and 24 hours postoperatively (P<0.001), but similar at 48 hours (P=0.164).

Conclusion:

Compared with the mTLIP block, the ESP block was associated with lower pain scores and a small decrease in perioperative fentanyl consumption in patients undergoing lumbar spine surgeries. Both blocks could form a part of a multimodal analgesic regimen in spine surgery patients.
Management of Air Leaks in the Newborn
Authors: Kastein Kim , Coe Kristi
Published: January 2023

Background:

Air leaks, especially pulmonary interstitial emphysema (PIE), are increasingly uncommon respiratory complications of the newborn. Despite PIE having a decreasing incidence, it continues to have a high morbidity and mortality rate. This makes PIE one of the most severe respiratory complications to affect a newborn. Air leaks occur when there is overdistension of the terminal airways or alveoli, which results in air dissecting into extra-alveolar spaces. Recognizing the signs of air leaks is paramount to allow for appropriate diagnosis and treatment of the newborn to improve morbidity and mortality. Treatment modalities range from positioning the newborn in the decubitus position to surgical intervention.

Purpose:

To summarize current evidence on the pathophysiology, risk factors, diagnosis, treatment, and management of PIE and pneumothorax.

Data Sources:

Two databases were systematically reviewed with key words later. Articles in English with date restrictions from 2016 to current were included.

Study Selection:

Inclusion criteria of randomized controlled trials, case studies/reports, and review articles were utilized. Twenty articles, primarily case reports and studies, were reviewed.

Data Extraction:

Guidelines for data abstraction were followed via independent extraction by a single observer.

Results:

Qualitative results were utilized to formulate current treatment of air leaks.

Implications for Practice:

This article provides guidance for frontline neonatal providers on current treatment and management of air leaks in the newborn population.
Resilience in Family Caregivers of Asian Older Adults With Dementia
Authors: Duangjina Thitinan , Fink Anne M. , Gruss Valerie
Published: February 2023

Asian family caregivers of older adults with dementia have stressful caregiving situations over long periods; they must become resilient to recover from adversity. A conceptual definition of resilience specific to Asian family caregivers is important for understanding their caregiving phenomena and the relationships with mental health and psychological well-being. The purpose of this concept analysis was to define resilience in family caregivers of Asian older adults with dementia using Walker and Avant's method. The findings of the analysis will guide future research about the modifiable factors that will prevent negative health outcomes in this population of caregivers.
Ogilvie Syndrome in Patients With Traumatic Pelvic and/or Acetabular Fractures: A Retrospective Cohort Study
Authors: Jensen Lasse Rehné , Possfelt-Møller Emma , Nielsen Allan Evald , Singh Upender Martin , Svendsen Lars Bo , Penninga Luit
Published: February 2023

Objectives:

To assess the incidence, risk factors, and clinical outcomes of Ogilvie syndrome (OS) in patients with pelvic and/or acetabular fractures.

Design:

Retrospective cohort study.

Setting:

Level 1 trauma center.

Patients:

One thousand sixty patients with pelvic and/or acetabular fractures treated at Rigshospitalet, Copenhagen, between 2009 and 2020.

Intervention:

Interventions comprised the treatment of pelvic and/or acetabular fractures with emergency external and/or internal fixation.

Main Outcome Measurements:

Outcomes included diagnosis of OS, perioperative complications, ICU stay and length, length of admission, and mortality.

Results:

We identified 1060 patients with pelvic and/or acetabular fractures. Of these, 25 patients were diagnosed with OS perioperatively, corresponding to incidences of 1.6%, 2.7%, and 2.6% for acetabular, pelvic, and combined fractures, respectively. Risk factors included congestive heart failure, diabetes, concomitant traumatic lesions, head trauma, fractures of the cranial vault and/or basal skull, retroperitoneal hematomas and spinal cord injuries, and emergency internal fixation and extraperitoneal packing. Six (24%) patients underwent laparotomy, and all patients had ischemia or perforation of the cecum for which right hemicolectomy was performed. Ogilvie syndrome was associated with a significant increase in nosocomial infections, sepsis, pulmonary embolism, ICU stay, and prolonged hospital admission.

Conclusion:

Ogilvie syndrome in patients with pelvic and/or acetabular fractures is associated with increased risk of perioperative complications and prolonged hospital and ICU stays, resulting in an increased risk of morbidity and mortality.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
A Staged Protocol for Treatment of High-Energy Tongue-Type Calcaneus Fractures: Surgical Technique and Case Series
Authors: Goodnough L. Henry , Bunzel Eli W. , Benirschke Stephen K. , Githens Michael F.
Published: February 2023

Displaced tongue-type calcaneus fractures are frequently associated with severe soft tissue injuries, and urgent relief of the displaced tongue fragment on the posterior soft tissues is essential to preventing soft tissue complications. If there is a complex articular injury, the soft tissue envelope often needs time for swelling to resolve to allow for a safe open anatomic reduction because premature open reduction internal fixation is often associated with increased complications. We have found that in high-energy tongue-type calcaneus fractures with complex articular injuries, a staged protocol consisting of initial percutaneous reduction and fixation with later definitive reconstruction is soft tissue friendly, allows early restoration of calcaneal morphology, and affords extensile approaches for eventual reconstruction. The purpose of this study was to describe our protocol of staged treatment of high-energy tongue-type calcaneus fractures, along with postoperative surgical outcomes, in a case series of 53 patients.

Our series of patients had a high rate of intra-articular injury with marked initial displacement (mean Bohler angle −8.4 ± 20.8 degrees). They were treated initially with percutaneous reduction and fixation at median 1 day postinjury (interquartile range [IQR] 0–1) and definitively at median 16 days postinjury (IQR 10–33). In this series, 2 of 53 (3.8%) patients developed a deep wound infection.

In high-energy tongue-type calcaneus fractures at risk for soft tissue compromise or with a significantly displaced tongue fragment without initial soft tissue compromise, we found that staged management represents a feasible management strategy to mitigate risk of soft tissue complications and therefore helps facilitate safe definitive open treatment.