bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative Moments of L–Functions With Small Shifts Over Function Fields
Authors: Florea Alexandra
Published: June 2023

We consider negative moments of quadratic Dirichlet $L$–functions over function fields. Summing over monic square-free polynomials of degree $2g+1$ in $\mathbb{F}_{q}[x]$, we obtain an asymptotic formula for the $k^{\textrm{th}}$ shifted negative moment of $L(1/2+\beta ,\chi _{D})$, in certain ranges of $\beta $ (e.g., when roughly $\beta \gg \log g/g $ and $k<1$). We also obtain non-trivial upper bounds for the $k^{\textrm{th}}$ shifted negative moment when $\log (1/\beta ) \ll \log g$. Previously, almost sharp upper bounds were obtained in [ 3] in the range $\beta \gg g^{-\frac{1}{2k}+\epsilon }$.
Integrating genomic prediction and genotype specific parameter estimation in ecophysiological models: overview and perspectives
Authors: Poudel Pratishtha , Naidenov Bryan , Chen Charles , Alderman Phillip D , Welch Stephen M
Published: June 2023

The Genome-to-Phenome (G2P) problem is one of the highest-priority challenges in applied biology. Ecophysiological crop models (ECM) and genomic prediction (GP) models are quantitative algorithms, which, when given information on a genotype and environment, can produce an accurate estimate of a phenotype of interest. In this article, we discuss how the GP algorithms can be used to estimate genotype-specific parameters (GSPs) in ECMs to develop robust prediction methods. In this approach, the numerical constants (GSPs) that ECMs use to distinguish and characterize crop cultivars/varieties are treated as quantitative traits to be predicted by genomic prediction models from underlying genetic information. In this article we provide information on which GP methods appear favorable for predicting different types of GSPs, such as vernalization sensitivity or potential radiation use efficiency. For each example GSP, we assess a number of GP methods in terms of their suitability using a set of three criteria grounded in genetic architecture, computational requirements, and the use of prior information. In general, we conclude that the most useful algorithms were dependent on both the nature of the particular GSP and the GP methods considered.
Should Canada adopt managed access agreements in Canada for expensive drugs?
Authors: McPhail Melanie , Bubela Tania
Published: June 2023

Drugs are increasingly authorized based on less mature evidence, leaving payors faced with significant clinical and cost-effectiveness uncertainties. As a result, payors must often choose between reimbursing a drug that may not turn out to be cost-effective (or may even be unsafe) or delaying the reimbursement of a drug that is cost-effective and offers clinical benefit to patients. Novel reimbursement decision models and frameworks, such as managed access agreements (MAAs), may address this decision challenge. Here, we provide a comprehensive overview of the legal limitations, considerations, and implications for adopting MAAs in Canadian jurisdictions. We begin with an overview of current drug reimbursement processes in Canada, terminology and definitions of the different types of MAAs, and select international experiences with MAAs. We discuss the legal barriers to MAA governance frameworks, design and implementation considerations, and legal and policy implications of MAAs. Finally, we provide recommendations to guide policy development for implementing MAAs in Canada, based on existing literature, international experience, and our legal analysis. We conclude that legal and policy barriers likely prevent the adoption of a pan-Canadian MAA governance framework. More feasible is a quasi-federal or provincial approach, building on existing infrastructure.
An unusual case of gallstone ileus within the cecum and ascending colon: a case report
Authors: Rana Asama , Hooda Zamaan , Kulkarni Sayali , Choi Karmina
Published: June 2023

Gallstone ileus is a rare cause of intestinal obstruction. Due to long-standing inflammation of the gallbladder, fistulization can occur within nearby structures, most commonly to the duodenum or hepatic flexure of the colon. Through these fistulas, a stone can migrate and result in a small bowel obstruction or a large bowel obstruction. This case exemplifies the diagnosis and treatment of gallstone ileus, along with potential complications due to stone migration. Early recognition and treatment of gallstone ileus is important, as stone migration can lead to increased mortality with delayed diagnosis.
Temperature–chemistry coupling in the evolution of gas giant atmospheres driven by stellar flares
Authors: Nicholls Harrison , Hébrard Eric , Venot Olivia , Drummond Benjamin , Evans Elise
Published: June 2023

The effect of enhanced UV irradiation associated with stellar flares on the atmospheric composition and temperature of gas giant exoplanets was investigated. This was done using a 1D radiative-convective-chemical model with self-consistent feedback between the temperature and the non-equilibrium chemistry. It was found that flare-driven changes to chemical composition and temperature give rise to prolonged trends in evolution across a broad range of pressure levels and species. Allowing feedback between chemistry and temperature plays an important role in establishing the quiescent structure of these atmospheres, and determines their evolution due to flares. It was found that cooler planets are more susceptible to flares than warmer ones, seeing larger changes in composition and temperature, and that temperature–chemistry feedback modifies their evolution. Long-term exposure to flares changes the transmission spectra of gas giant atmospheres; these changes differed when the temperature structure was allowed to evolve self-consistently with the chemistry. Changes in spectral features due to the effects of flares on these atmospheres can be associated with changes in composition. The effects of flares on the atmospheres of sufficiently cool planets will impact observations made with JWST. It is necessary to use self-consistent models of temperature and chemistry in order to accurately capture the effects of flares on features in the transmission spectra of cooler gas giants, but this depends heavily on the radiation environment of the planet.
Three low-mass companions around aged stars discovered by TESS
Authors: Lin Zitao , Gan Tianjun , Wang Sharon X , Shporer Avi , Rabus Markus , Zhou George , Psaridi Angelica , Bouchy François , Bieryla Allyson , Latham David W , Mao Shude , Stassun Keivan G , Hellier Coel , Howell Steve B , Ziegler Carl , Caldwell Douglas A , Clark Catherine A , Collins Karen A , Curtis Jason L , Faherty Jacqueline K , Gnilka Crystal L , Grunblatt Samuel K , Jenkins Jon M , Johnson Marshall C , Law Nicholas , Lendl Monika , Littlefield Colin , Lund Michael B , Lund Mikkel N , Mann Andrew W , McDermott Scott , Mishra Lokesh , Mounzer Dany , Paegert Martin , Pritchard Tyler , Ricker George R , Seager Sara , Srdoc Gregor , Sun Qinghui , Tang Jiaxin , Udry Stéphane , Vanderspek Roland , Watanabe David , Winn Joshua N , Yu Jie
Published: June 2023

We report the discovery of three transiting low-mass companions to aged stars: a brown dwarf (TOI-2336b) and two objects near the hydrogen burning mass limit (TOI-1608b and TOI-2521b). These three systems were first identified using data from the Transiting Exoplanet Survey Satellite (TESS). TOI-2336b has a radius of 1.05 ± 0.04 RJ, a mass of 69.9 ± 2.3 MJ and an orbital period of 7.71 d. TOI-1608b has a radius of 1.21 ± 0.06 RJ, a mass of 90.7 ± 3.7 MJ and an orbital period of 2.47 d. TOI-2521b has a radius of 1.01 ± 0.04 RJ, a mass of 77.5 ± 3.3 MJ, and an orbital period of 5.56 d. We found all these low-mass companions are inflated. We fitted a relation between radius, mass, and incident flux using the sample of known transiting brown dwarfs and low-mass M dwarfs. We found a positive correlation between the flux and the radius for brown dwarfs and for low-mass stars that is weaker than the correlation observed for giant planets. We also found that TOI-1608 and TOI-2521 are very likely to be spin-orbit synchronized, leading to the unusually rapid rotation of the primary stars considering their evolutionary stages. Our estimates indicate that both systems have much shorter spin-orbit synchronization time-scales compared to their ages. These systems provide valuable insights into the evolution of stellar systems with brown dwarf and low-mass stellar companions influenced by tidal effects.
Secular dynamics of stellar spin driven by planets inside Kozai–Lidov resonance
Authors: Lei Hanlun , Gong Yan-Xiang
Published: June 2023

In many exoplanetary systems with ‘hot Jupiters’, it is observed that the spin axes of host stars are highly misaligned to planetary orbital axes. In this study, a possible channel is investigated for producing such a misalignment under a hierarchical three-body system, where the evolution of stellar spin is subjected to the gravitational torque induced from the planet inside Kozai–Lidov (KL) resonance. In particular, two special configurations are explored in detail. The first one corresponds to the configuration with planets at KL fixed points, and the second one corresponds to the configurations with planets moving on KL librating cycles. When the planet is located at the KL fixed point, the corresponding Hamiltonian model is of one degree of freedom and there are three branches of libration centres for stellar spin. When the planet is moving on KL cycles, the technique of Poincaré section is taken to reveal global structures of stellar spin in phase space. To understand the complex structures, perturbative treatments are adopted to study rotational dynamics. It shows that analytical structures in phase portraits under the resonant model can agree well with numerical structures arising in Poincaré sections, showing that the complicated dynamics of stellar spin are governed by the primary resonance under the unperturbed Hamiltonian model in combination with the 2:1 (high-order and/or secondary) spin–orbit resonances.
Safety of multiple administrations of spermicidal LL-37 antimicrobial peptide into the mouse female reproductive tract
Authors: Lee Seung Gee , Kiattiburut Wongsakorn , Burke Schinkel Stephanie C , Angel Jonathan , Tanphaichitr Nongnuj
Published: June 2023

We have previously demonstrated spermicidal activity of LL-37 antimicrobial peptide on mouse/human sperm and its contraceptive effects in female mice. With its microbicidal action against Neisseria gonorrhoeae, LL-37 warrants development into a multipurpose prevention technology (MPT) agent for administering into the female reproductive tract (FRT). However, it is important to verify that multiple administrations of LL-37 do not lead to damage of FRT tissues and/or irreversible loss of fecundity. Herein, we transcervically injected LL-37 (36 µM–10× spermicidal dose) into female mice in estrus in three consecutive estrous cycles. A set of mice were sacrificed for histological assessment of the vagina/cervix/uterus 24 h after the last injection, while the second set were artificially inseminated with sperm from fertile males 1 week afterwards, and then monitored for pregnancy. Mice injected with PBS in parallel were regarded as negative controls, whereas those injected with vaginal contraceptive foam (VCF, available over the counter), containing 12.5% nonoxynol-9, served as positive controls for vaginal epithelium disruption. We demonstrated that the vagina/cervix/uterus remained normal in both LL-37-injected and PBS-injected mice, which also showed 100% resumption of fecundity. In contrast, VCF-injected mice showed histological abnormalities in the vagina/cervix/uterus and only 50% of them resumed fecundity. Similarly, LL-37 multiply administered intravaginally caused no damage to FRT tissues. While our results indicate the safety of multiple treatments of LL-37 in the mouse model, similar studies have to be conducted in non-human primates and then humans. Regardless, our study provides an experimental model for studying in vivo safety of other vaginal MPT/spermicide candidates.
RIG-I recognizes metabolite-capped RNAs as signaling ligands
Authors: Schweibenz Brandon D , Solotchi Mihai , Hanpude Pranita , Devarkar Swapnil C , Patel Smita S
Published: June 2023

The innate immune receptor RIG-I recognizes 5′-triphosphate double-stranded RNAs (5′ PPP dsRNA) as pathogenic RNAs. Such RNA-ends are present in viral genomes and replication intermediates, and they activate the RIG-I signaling pathway to produce a potent interferon response essential for viral clearance. Endogenous mRNAs cap the 5′ PPP-end with m7G and methylate the 2′-O-ribose to evade RIG-I, preventing aberrant immune responses deleterious to the cell. Recent studies have identified RNAs in cells capped with metabolites such as NAD+, FAD and dephosphoCoA. Whether RIG-I recognizes these metabolite-capped RNAs has not been investigated. Here, we describe a strategy to make metabolite-capped RNAs free from 5′ PPP dsRNA contamination, using in vitro transcription initiated with metabolites. Mechanistic studies show that metabolite-capped RNAs have a high affinity for RIG-I, stimulating the ATPase activity at comparable levels to 5′ PPP dsRNA. Cellular signaling assays show that the metabolite-capped RNAs potently stimulate the innate antiviral immune response. This demonstrates that RIG-I can tolerate diphosphate-linked, capped RNAs with bulky groups at the 5′ RNA end. This novel class of RNAs that stimulate RIG-I signaling may have cellular roles in activating the interferon response and may be exploited with proper functionalities for RIG-I-related RNA therapeutics.
Deep proteome investigation of high-grade gliomas reveals heterogeneity driving differential metabolism of 5-aminolevulinic acid
Authors: Ghantasala Saicharan , Bhat Amruth , Agarwal Unnati , Biswas Deeptarup , Bhattarai Prawesh , Epari Sridhar , Moiyadi Aliasgar , Srivastava Sanjeeva
Published: June 2023

Background

Fluorescence-guided surgery (FGS) using 5-aminolevulinic acid (5-ALA) as adjunct for high-grade gliomas (HGGs) has been on the rise in recent years. Despite being largely effective, we observed multiple histologically similar sub-regions of the same tumor from a few individuals with varying protoporphyrin IX (PpIX) levels. The current study aims at understanding the proteomic changes driving differential metabolism of 5-ALA in HGGs.

Methods

Biopsies were histologically and biochemically assayed. Following this, a deep proteomics investigation was carried out using high resolution liquid chromatography—mass spectrometry (HR LC-MS) to identify protein expression in differentially fluorescing regions of HGGs.

Results

Our analysis identified 5437 proteins with high confidence. Differential analysis in the subgroup with HGGs carrying IDH mutation (IDH mt.) revealed 93 differentially regulated proteins (raw p-value ≤ 0.05 and absolute FC ≥ 1.5). Similar analysis in the IDH wild type (IDH wt.) subgroup revealed 20 differentially regulated proteins. Gene set enrichment analysis (GSEA) identified key pathways like ion channel transport, trafficking of AMPA receptors, and regulation of heme-oxygenase-1 in the IDH wt. subgroup. Pathways such as scavenging of heme, signaling by NOTCH4, negative regulation of PI3-AKT pathway, and iron uptake and transport were observed to be differentially regulated in the IDH mt. subgroup.

Conclusions

Tumor regions from the same patient exhibiting differential fluorescence following 5-ALA administration were observed to have different proteome profiles. Future studies aimed at a better molecular understanding of 5-ALA metabolism in HGGs hold the potential to increase the efficacy of FGS and the use of 5-ALA as a theragnostic tool.
Retrospective and Real-time Measures of the Quantity of E-cigarette Use: An Ecological Momentary Assessment Study
Authors: Yang James J , Ou Tzung-Shiang , Lin Hsien-Chang , Kyung Nam Joon , Piper Megan E , Buu Anne
Published: June 2023

Introduction

Quantifying e-cigarette use is challenging because of the wide variety of products and the lack of a clear, objective demarcation of a use event. This study aimed to characterize the difference between retrospective and real-time measures of the quantity of e-cigarette use and identify the covariates that may account for discrepancies between the two types of measures.

Methods

This study analyzed data from 401 college student e-cigarette users in Indiana and Texas who responded to a web survey (retrospective) and 7-day ecological momentary assessments (EMA) (real-time) on their e-cigarette use behavior, dependence symptomatology, e-cigarette product characteristics, and use contexts from Fall 2019 to Fall 2021. Generalized linear mixed models were used to model the real-time measures of quantity offset by the retrospective average quantity.

Results

Although the number of times using e-cigarettes per day seems to be applicable to both retrospective and real-time measures, the number reported via EMA was 8.5 times the retrospective report. E-cigarette users with higher e-cigarette primary dependence motives tended to report more daily nicotine consumption via EMA than their retrospective reports (ie, perceived average consumption). Other covariates that were associated with discrepancies between real-time and retrospective reports included gender, nicotine concentration, using a menthol- or fruit-flavored product, co-use with alcohol, and being with others when vaping,

Conclusions

The study found extreme under-reporting of e-cigarette consumption on retrospective surveys. Important covariates identified to be associated with higher than average consumption may be considered as potential targets for future vaping interventions.

Implications

This is the first study that characterizes the direction and magnitude of the difference between retrospective and real-time measures of the quantity of e-cigarette use among young adults—the population most likely to use e-cigarettes. An average retrospective account of vaping events per day may significantly underestimate e-cigarette use frequency among young adults. The lack of insight into the degree of consumption among users with heavy primary dependence motives illustrates the importance of incorporating self-monitoring into cessation interventions.
Cash versus lottery video messages: online COVID-19 vaccine incentives experiment
Authors: Duch Raymond M , Barnett Adrian , Filipek Maciej , Espinosa-Brito Javier , Roope Laurence S J , Violato Mara , Clarke Philip M
Published: June 2023

During the COVID-19 pandemic, governments offered financial incentives to increase vaccine uptake. We evaluate the impact on COVID-19 vaccine uptake of cash equivalents versus being entered into lotteries. We randomly assign 1628 unvaccinated US participants into one of three 45-second informational videos promoting vaccination with messages about (a) health benefits of COVID-19 vaccines (control), (b) being entered into lotteries or (c) receiving cash equivalent vouchers. After seeing the control health information video, 16% of individuals wanted information on COVID-19 vaccination. This compared with 14% of those assigned to the lottery video (odds ratio of 0.82 relative to control: 95% credible interval, 0.58–1.17) and 22% of those assigned to the cash voucher video (odds ratio of 1.53 relative to control: 95% credible interval, 1.11–2.11). These results support greater use of cash vouchers to promote information seeking about COVID-19 vaccination and do not support the use of lottery incentives.
Age as a moderator in the interplay among locus of control, coping, and quality of life of people with chronic pain
Authors: Kłosowska Joanna , Farley Dominika , Brączyk Justyna , Buglewicz-Przewoźnik Ewa , Bąbel Przemysław
Published: June 2023

Objective

Identifying the factors that determine the quality of life of patients with chronic pain is an integral part of developing interventions to reduce the negative impact of persistent pain. Locus of control (LoC) could play an important role in adaptation to prolonged pain, but the results of studies are inconsistent. We examined the link between pain LoC and quality of life. Moreover, we investigated whether the relationship between LoC and quality of life is mediated by passive and active coping, and whether age moderates the LoC–coping relationship.

Methods

The study was cross-sectional, and variables (internal, chance and powerful-others LoC, pain coping strategies, average pain intensity, and quality of life) were assessed via questionnaires in a sample of 594 individuals (67% females) with chronic pain who were 18–72 (mean: 36) years of age.

Results

Mediation and moderated mediation analyses were conducted. Internal and external LoC were associated, respectively, with better and with worse quality of life. Passive coping mediated the association between the powerful-others dimension of LoC and poor quality of life. Additionally, indirect effects of internal LoC on quality of life via passive and active coping were found. The relationship between the powerful-others dimension of LoC and coping was stronger for middle-aged and older individuals than for younger individuals.

Conclusions

This study contributes to a better understanding of the mechanisms linking LoC with quality of life of patients with chronic pain. Depending on the age, control beliefs might translate differently into strategies used to cope with pain, and thus into quality of life.
Exploring the treatment burden of disease-modifying anti-rheumatic drug monitoring in people with rheumatoid arthritis
Authors: Ryan Sarah , Bullock Laurna , Manning Fay , A. Chew-Graham Carolyn , Paskins Zoe
Published: June 2023

Objectives

People with RA taking DMARDs require safety monitoring to identify potential side effects. The aim of this study was to explore the perspectives of patients and family members on DMARD monitoring and how the associated treatment burden could be minimized to optimize concordance and safety.

Methods

Thirteen adults with RA on DMARDs and three family members participated in semi-structured telephone interviews between July 2021 and January 2022. Data were analysed using a framework method. Findings were discussed with a group of stakeholders to develop implications for practice.

Results

Two main themes were identified: (i) making sense of drug monitoring; and (ii) work involved in drug monitoring. Participants perceived DMARDs as necessary to reduce symptoms, with drug monitoring providing an opportunity for a holistic assessment of wellbeing. Participants expressed a preference for face-to-face consultations, which allowed them to share their concerns, rather than remote, often transactional, care. The limited availability of convenient appointment times, travel requirements and parking increased the work involved for patients and family members.

Conclusion

Drug monitoring was accepted as a necessity of DMARD treatment, but increased the work for people with RA related to organizing and attending appointments. The potential for treatment burden needs to be assessed proactively by clinicians when a DMARD is commenced. Where identified, strategies for minimizing the treatment burden can form part of a shared management plan, including the offer of regular contact with health professionals, with an emphasis on person-centred care.
Azathioprine vs methotrexate in eosinophilic granulomatosis with polyangiitis: a monocentric retrospective study
Authors: Milanesi Alessandra , Delvino Paolo , Quaglini Silvana , Montecucco Carlomaurizio , Monti Sara
Published: June 2023

Objectives

To analyse the effectiveness, safety and steroid-sparing effect of AZA and MTX as induction of remission and maintenance treatment in eosinophilic granulomatosis with polyangiitis.

Methods

We retrospectively collected data from 57 patients divided into four groups according to treatment: MTX/AZA as first-line agents (MTX1/AZA1) in non-severe disease or as second-line maintenance therapy (MTX2/AZA2) in severe disease previously treated with CYC/rituximab. During the first 5 years of treatment with AZA/MTX we compared the groups according to: remission rate [defined as R1: BVAS = 0; R2: BVAS = 0 with prednisone ≤5 mg/day; R3 (MIRRA definition): BVAS = 0 with prednisone ≤3.75 mg/day], persistence on therapy, cumulative glucocorticoid (GC) dose, relapse and adverse events (AEs).

Results

There were no significant differences in remission rates (R1) in each group (63% in MTX1 vs 75% in AZA1, P = 0.53; 91% in MTX2 vs 71% in AZA2, P = 0.23). MTX1 allowed R2 more frequently in the first 6 months compared with AZA1 (54% vs 12%, P = 0.04); no patients receiving AZA1 achieved R3 up to the first 18 months (vs 35% in MTX1, P = 0.07). The cumulative GC dose was lower for MTX2 vs AZA2 (6 g vs 10.7 g at 5 years, P = 0.03). MTX caused more AEs compared with AZA (66% vs 30%, P = 0.004), without affecting the suspension rate. No differences emerged in time-to-first relapse, although fewer patients treated with AZA2 had asthma/ENT relapses (23% vs 64%, P = 0.04).

Conclusion

A significant proportion of patients achieved remission with both MTX and AZA. MTX1 had an earlier remission on a lower GC dose but MTX2 had a better steroid-sparing effect.
5Ecocriticism
Authors: Ryan John Charles
Published: June 2023

This review of ecocritical publications in 2022 is divided into six sections: 1. Introduction: Ecocriticism in the Anthropocene; 2. Eco-modernism: The Environmental Turn in Modernist Studies; 3. Climate Criticism: Narratives of Vulnerability; 4. Cryocriticism: Biographies of Ice; 5. More-than-Human Ecocriticism: The Heterogeneities of Nature; 6. Conclusion: Ecocriticism and Transformation.
Stem Cell Therapy Enriched Fat Grafting for the Reconstruction of Craniofacial Deficits
Authors: Bourne Debra A. , Egro Francesco M. , Bliley Jacqueline , James Isaac , Haas Gretchen L. , Meyer E. Michael , Donnenberg Vera , Donnenberg Albert D. , Branstetter Barton , Coleman Sydney , Rubin J. Peter
Published: June 2023

Background:

Fat grafting is an effective treatment for craniofacial deformities. Stromal vascular fraction (SVF) is a concentrated form of adipose derived stem cells that can be isolated from fat. The aim of this clinical trial was to assess the impact of SVF enrichment on craniofacial fat grafting.

Methods:

Twelve subjects with at least two regions of craniofacial volume deficit were enrolled, and they underwent fat grafting with SVF-enriched or standard fat grafting to each area. All patients had bilateral malar regions injected with SVF-enriched graft on one side and control standard fat grafting to the contralateral side. Outcome assessments included demographic information, volume retention determined by CT scans, SVF cell populations assessed by flow cytometry, SVF cell viability, complications, and appearance ratings. Follow-up was 9 months.

Results:

All patients had improvement in appearance. There were no serious adverse events. There was no significant difference in volume retention between the SVF-enriched and control regions overall (50.3% versus 57.3%, P = 0.269) or comparing malar regions (51.4% versus 56.7%, P = 0.494). Patient age, smoking status, obesity, and diagnosis of diabetes did not impact volume retention. Cell viability was 77.4% ± 7.3%. Cellular subpopulations were 60.1% ± 11.2% adipose derived stem cells, 12.2 ± 7.0% endothelial cells, and 9.2% ± 4.4% pericytes. A strong positive correlation was found between CD146+ CD31-pericytes and volume retention (R = 0.863, P = 0.027).

Conclusions:

Autologous fat transfer for reconstruction of craniofacial defects is effective and safe, leading to reliable volume retention. However, SVF enrichment does not significantly impact volume retention.
Current status and practical considerations of artificial intelligence use in screening and diagnosing retinal diseases: Vision Academy retinal expert consensus
Authors: Chou Yu-Bai , Kale Aditya U. , Lanzetta Paolo , Aslam Tariq , Barratt Jane , Danese Carla , Eldem Bora , Eter Nicole , Gale Richard , Korobelnik Jean-François , Kozak Igor , Li Xiaorong , Li Xiaoxin , Loewenstein Anat , Ruamviboonsuk Paisan , Sakamoto Taiji , Ting Daniel S.W. , van Wijngaarden Peter , Waldstein Sebastian M. , Wong David , Wu Lihteh , Zapata Miguel A. , Zarranz-Ventura Javier
Published: June 2023

Purpose of review

The application of artificial intelligence (AI) technologies in screening and diagnosing retinal diseases may play an important role in telemedicine and has potential to shape modern healthcare ecosystems, including within ophthalmology.

Recent findings

In this article, we examine the latest publications relevant to AI in retinal disease and discuss the currently available algorithms. We summarize four key requirements underlining the successful application of AI algorithms in real-world practice: processing massive data; practicability of an AI model in ophthalmology; policy compliance and the regulatory environment; and balancing profit and cost when developing and maintaining AI models.

The Vision Academy recognizes the advantages and disadvantages of AI-based technologies and gives insightful recommendations for future directions.
Longitudinal Assessment of Retinal Nerve Fiber Layer and Ganglion Cell Complex Thicknesses in Patients With Large Optic Disc Cups and Normal Intraocular Pressure and Visual Fields
Authors: Kang Eun Jin , Jin Sang Wook
Published: June 2023

Précis:

The thicknesses of the circumpapillary retinal nerve fiber layer (cpRNFL) and ganglion cell complex (GCC) did not change during 5 years in physiological large disc cupping.

Purpose:

We evaluated longitudinal changes in the thicknesses of the cpRNFL and GCC in large disc cupping with a normal intraocular pressure (IOP) (<21 mm Hg) and visual field.

Methods:

This retrospective, consecutive case series study included 269 eyes of 269 patients with large disc cupping and normal IOP. We analyzed patient demographics, IOP, central corneal thickness, vertical cup-to-disc ratios using color fundus photography, the thicknesses of the cpRNFL and GCC using RTVue-100, and mean deviation using visual field examinations.

Results:

The differences in IOP, vertical cup-to-disc ratios, and mean deviation between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the cpRNFL thickness were 106.5±8.5 and 105.1±9.3 μm, respectively; differences between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the GCC thickness were 82.8±9. and 81.5±9.2 μm, respectively; differences between baseline and each follow-up visit were not statistically significant.

Conclusions:

The thicknesses of the cpRNFL and GCC did not change in well-maintained optic nerve head findings with normal IOP and visual field during a 5-year follow-up period. Optical coherence tomography evaluations of the thicknesses of the cpRNFL and GCC help accurately diagnose physiological optic disc cupping.
Augmented pain-evoked primary sensorimotor cortex activation in adolescent girls with juvenile fibromyalgia
Authors: Tong Han , Maloney Thomas C. , Payne Michael F. , Suñol Maria , Dudley Jonathan A. , King Christopher D. , Ting Tracy V. , Kashikar-Zuck Susmita , Coghill Robert C. , López-Solà Marina
Published: June 2023

Juvenile fibromyalgia (JFM) is a chronic widespread pain condition that primarily affects adolescent girls. Previous studies have found increased sensitivity to noxious pressure in adolescents with JFM. However, the underlying changes in brain systems remain unclear. The aim of this study was to characterize pain-evoked brain responses and identify brain mediators of pain hypersensitivity in adolescent girls with JFM. Thirty-three adolescent girls with JFM and 33 healthy adolescent girls underwent functional magnetic resonance imaging scans involving noxious pressure applied to the left thumbnail at an intensity of 2.5 or 4 kg/cm2 and rated pain intensity and unpleasantness on a computerized Visual Analogue Scale. We conducted standard general linear model analyses and exploratory whole-brain mediation analyses. The JFM group reported significantly greater pain intensity and unpleasantness than the control group in response to noxious pressure stimuli at both intensities (P < 0.05). The JFM group showed augmented right primary somatosensory cortex (S1) activation to 4 kg/cm2 (Z > 3.1, cluster-corrected P < 0.05), and the peak S1 activation magnitudes significantly correlated with the scores on the Widespread Pain Index (r = 0.35, P = 0.048) with higher activation associated with more widespread pain. We also found that greater primary sensorimotor cortex activation in response to 4 kg/cm2 mediated the between-group differences in pain intensity ratings (P < 0.001). In conclusion, we found heightened sensitivity to noxious pressure stimuli and augmented pain-evoked sensorimotor cortex responses in adolescent girls with JFM, which could reflect central sensitization or amplified nociceptive input.
Morphine-induced osteolysis and hypersensitivity is mediated through toll-like receptor-4 in a murine model of metastatic breast cancer
Authors: Thompson Austen L. , Grenald Shaness A. , Ciccone Haley A. , Mohty Dieter , Smith Angela F. , Coleman Deziree L. , Bahramnejad Erfan , De Leon Erick , Kasper-Conella Logan , Uhrlab Jennifer L. , Margolis David S. , Salvemini Daniela , Largent-Milnes Tally M. , Vanderah Todd W.
Published: June 2023

The propensity for breast cancer to metastasize to bone is coupled to the most common complaint among breast cancer patients: bone pain. Classically, this type of pain is treated using escalating doses of opioids, which lack long-term efficacy due to analgesic tolerance, opioid-induced hypersensitivity, and have recently been linked to enhanced bone loss. To date, the molecular mechanisms underlying these adverse effects have not been fully explored. Using an immunocompetent murine model of metastatic breast cancer, we demonstrated that sustained morphine infusion induced a significant increase in osteolysis and hypersensitivity within the ipsilateral femur through the activation of toll-like receptor-4 (TLR4). Pharmacological blockade with TAK242 (resatorvid) as well as the use of a TLR4 genetic knockout ameliorated the chronic morphine-induced osteolysis and hypersensitivity. Genetic MOR knockout did not mitigate chronic morphine hypersensitivity or bone loss. In vitro studies using RAW264.7 murine macrophages precursor cells demonstrated morphine-enhanced osteoclastogenesis that was inhibited by the TLR4 antagonist. Together, these data indicate that morphine induces osteolysis and hypersensitivity that are mediated, in part, through a TLR4 receptor mechanism.
Evolving acidic microenvironments during colitis provide selective analgesic targets for a pH-sensitive opioid
Authors: Degro Claudius E. , Jiménez-Vargas Nestor Nivardo , Tsang Quentin , Yu Yang , Guzman-Rodriguez Mabel , Alizadeh Elahe , Hurlbut David , Reed David E. , Lomax Alan E. , Stein Christoph , Bunnett Nigel W. , Vanner Stephen J.
Published: June 2023

Targeting the acidified inflammatory microenvironment with pH-sensitive opioids is a novel approach for managing visceral pain while mitigating side effects. The analgesic efficacy of pH-dependent opioids has not been studied during the evolution of inflammation, where fluctuating tissue pH and repeated therapeutic dosing could influence analgesia and side effects. Whether pH-dependent opioids can inhibit human nociceptors during extracellular acidification is unexplored. We studied the analgesic efficacy and side-effect profile of a pH-sensitive fentanyl analog, (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), during the evolution of colitis induced in mice with dextran sulphate sodium. Colitis was characterized by granulocyte infiltration, histological damage, and acidification of the mucosa and submucosa at sites of immune cell infiltration. Changes in nociception were determined by measuring visceromotor responses to noxious colorectal distension in conscious mice. Repeated doses of NFEPP inhibited nociception throughout the course of disease, with maximal efficacy at the peak of inflammation. Fentanyl was antinociceptive regardless of the stage of inflammation. Fentanyl inhibited gastrointestinal transit, blocked defaecation, and induced hypoxemia, whereas NFEPP had no such side effects. In proof-of-principle experiments, NFEPP inhibited mechanically provoked activation of human colonic nociceptors under acidic conditions mimicking the inflamed state. Thus, NFEPP provides analgesia throughout the evolution of colitis with maximal activity at peak inflammation. The actions of NFEPP are restricted to acidified layers of the colon, without common side effects in normal tissues.N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide could provide safe and effective analgesia during acute colitis, such as flares of ulcerative colitis.
Minority hair tax: pricing bias in haircare products
Authors: Sow Yacine N. , Onalaja-Underwood Amanda A. , Jackson Tiaranesha K. , Taylor Susan C. , Ogunleye Temitayo A.
Published: June 2023

Background:

Black haircare is an estimated $2.51-billion-dollar industry. Black women spend 9 times more on ethnic hair products than non-Black consumers. The haircare industry has adapted to these market trends by developing products catering to the needs of “natural hair,” referring to curly to tightly coiled hair texture that has not been chemically straightened with a relaxer. Anecdotally, natural haircare products are relatively expensive.

Objective:

We aimed to investigate texture-based price differences for haircare products targeting coily/curly compared to straight hair types.

Methods:

Data were collected in August 2022 from 6 brands available on www.amazon.com. After stratifying the data by manufacturer, hair texture, and average price/oz, we used 2 sample t-test with equal variances to examine cost differences.

Results:

Overall, there was a significant difference in average price/oz between all coily/curly and straight hair products, with coily/curly hair products being more expensive. When stratified by manufacturer, one leading US manufacturer sold coily/curly hair products at a higher price ($0.66/oz ±$0.05) compared with straight hair products ($0.46/oz ±$0.04), t
14 = 2.8967, P < 0.0134.

Limitations:

A small sample size of only shampoos and conditioners were analyzed, which may not represent the number of haircare products that consumers use.

Conclusion:

Pricing policies should ensure that all individuals have access to effective, affordable haircare products. Dermatologists should also be cognizant of pricing differences to direct patients with natural hair to fairly priced products.
Urolithiasis in patients with inflammatory bowel disease: A systematic review and meta-analysis of 13,339,065 individuals
Authors: Abdulrhman Aldukhayel , Alsweed Adil , Alotaibi May Rashed , Aldakhil Abdullah Yousef , Alahmadi Shahad Fahad , Albishri Saud Musallum , Alhmed Nurah Ibrahem
Published: June 2023

Background:

This study aimed to summarize the current literature regarding the prevalence of renal stones in patients with inflammatory bowel disease (IBD). Moreover, we aimed to evaluate the risk factors of urolithiasis in patients with IBD and the difference between patients with IBD and healthy controls in terms of urinary profile.

Methods:

On February 23, 2022, a computerized search was conducted on PubMed, OVID via MEDLINE, Web of Science, and Scopus using relevant keywords. Three independent reviewers performed 2-stage screening and data extraction. The National Institutes of Health tools were employed for quality assessment. Review Manager 5.4 software was used to calculate the mean difference (MD) between IBD patients and non-IBD in terms of urine profile using the Inverse-variance model and to estimate the odds ratio of reported risk factors for renal stones with the Generic Inverse-Variance model.

Results:

Thirty-two articles (n = 13,339,065 patients) were included. The overall prevalence of renal stones in patients with IBD was 6.3%, 95% Confidence interval (4.8%–8.3%). The prevalence of urolithiasis was more common in Chron’s disease vs Ulcerative colitis (7.9% vs 5.6%) and in old studies (1964–2009) than in more recent studies (2010–2022) (7.3% vs 5.2%), respectively. Compared to non-IBD patients, patients with IBD were associated with significantly lower urine volume (MD = −518.84 mL/day, P < .00001), calcium 24-hour urine (MD = −28.46 mg/day, P < .0001), citrate 24-hour urine (MD = −144.35 mg/day, P < .00001), sodium 24-hour urine (MD = −23.72 mg/day, P = .04), and magnesium 24-hour urine (MD = −33.25 mg/day, P < .00001).

Conclusion:

The overall prevalence of renal stones in patients with IBD was comparable to the general population. Patients with Chron’s disease were associated with a higher prevalence of urolithiasis compared to Ulcerative colitis. Drugs that induce renal calculi should be stopped in high-risk patients.
Case report: Gitelman syndrome with diabetes: Confirmed by both hydrochlorothiazide test and genetic testing
Authors: Yang Luyang , Fan Jinmeng , Liu Yunfeng , Ren Yi , Liu Zekun , Fu Hairui , Qi Hao , Yang Jing
Published: June 2023

Rationale:

Gitelman syndrome (GS) is an autosomal recessive tubulopathy caused by mutations of the SLC12A3 gene. It is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. Hypokalemia, hypomagnesemia, and increased renin-angiotensin-aldosterone system (RAAS) activity can cause glucose metabolism dysfunction. The diagnosis of GS includes clinical diagnosis, genetic diagnosis and functional diagnosis. The gene diagnosis is the golden criterion while as functional diagnosis is of great value in differential diagnosis. The hydrochlorothiazide (HCT) test is helpful to distinguish GS from batter syndrome, but few cases have been reported to have HCT testing.

Patient concerns:

A 51-year-old Chinese woman presented to emergency department because of intermittent fatigue for more than 10 years.

Diagnoses:

Laboratory test results showed hypokalemia, hypomagnesemia, hypocalciuria and metabolic alkalosis. The HCT test showed no response. Using next-generation and Sanger sequencing, we identified 2 heterozygous missense variants (c.533C > T:p.S178L and c.2582G > A:p.R861H) in the SLC12A3 gene. In addition, the patient was diagnosed with type 2 diabetes mellitus 7 years ago. Based on these findings, the patient was diagnosed with GS with type 2 diabetic mellitus (T2DM).

Interventions:

She was given potassium and magnesium supplements, and dapagliflozin was used to control her blood glucose.

Outcomes:

After treatments, her fatigue symptoms were reduced, blood potassium and magnesium levels were increased, and blood glucose levels were well controlled.

Lessons:

When GS is considered in patients with unexplained hypokalemia, the HCT test can be used for differential diagnosis, and genetic testing can be continued to confirm the diagnosis when conditions are available. GS patients often have abnormal glucose metabolism, which is mainly caused by hypokalemia, hypomagnesemia, and secondary activation of RAAS. When a patient is diagnosed with GS and type 2 diabetes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) can be used to control the blood glucose level and assist in raising blood magnesium.
Prevalence and risk factors for severe linezolid-associated thrombocytopenia in pediatric patients: An analysis of a public database
Authors: Yang Shibo , Guo Wencheng , Chen Ming , Hu Jindong , Feng Nana , Ju Mohan , Qian Yiyi
Published: June 2023

Linezolid is widely used in various clinical settings. Studies have revealed that it may cause thrombocytopenia in adults. However, the correlation between the use of linezolid and thrombocytopenia in pediatric patients is still unclear. This study aimed to identify the impact of Linezolid on the occurrence of thrombocytopenia in children. A retrospective observational study was conducted using data on patients treated with linezolid from the Pediatric Intensive Care clinical database. Univariate and multiple logistic regression analyses were performed to identify the risk factors of linezolid-related severe thrombocytopenia. A total of 134 patients were included. The prevalence of severe thrombocytopenia was 8.96% (12/134). Univariate analysis indicated that the severe thrombocytopenia group showed significantly higher proportion of concomitant carbapenem (75% vs 44.3%; P < .05) and piperacillin/tazobactam (25% vs 6.6%; P < .05) than that of the non-severe thrombocytopenia group. Multivariate analysis also revealed that the occurrence of severe thrombocytopenia was significantly associated with concurrent use of carbapenem (odd ratio = 4.058; 95% confidence interval: 1.012–16.274; P = .048) and piperacillin/tazobactam (odd ratio = 5.335; 95% confidence interval: 1.117–25.478; P = .036). 75% of patients (9/12) developed severe thrombocytopenia within the first 7 days of linezolid use. The concomitant use of carbapenem and piperacillin/tazobactam was associated with an increased probability of severe thrombocytopenia in pediatric patients undergoing linezolid treatment. Further prospective clinical studies are required, and more detailed mechanisms of blood toxicity in pediatric patients must be investigated.
A Comparison of the 1918 and 2019 Pandemics in the United States
Authors: Baldwin Kathleen M. , Gray Shara
Published: June 2023

There are eerie similarities between the 1918 Spanish influenza and 2019 COVID-19 pandemics that are somewhat surprising and disheartening, given that the time interval between the 2 pandemics is more than 100 years. This article covers the national response, etiology and pathophysiology, disease course and treatments, nursing shortages, healthcare responses, sequelae following infections, and economic and social impacts of both pandemics. Understanding the development and course of both pandemics will inform clinical nurse specialists about the changes that need to be made to be better prepared to recognize the changes that need to be made to prepare for the next pandemic.
Self-efficacy in Clinical Nurse Specialists During the COVID-19 Pandemic
Authors: Greenwood Wendy D. , Bishop Pamela
Published: June 2023

Purpose

The purpose of this study was to examine the perceived self-efficacy of the clinical nurse specialist working in the United States during the COVID-19 pandemic and explore whether there was any difference in self-efficacy based on practice focus (spheres of impact) and if differences existed between self-efficacy and demographics.

Design

This study used a nonexperimental, correlational, cross-sectional design utilizing a voluntary, anonymous, 1-time survey administered through Qualtrics (Qualtrics, Provo, UT).

Methods

The National Association of Clinical Nurse Specialists and 9 state affiliates distributed the electronic survey starting late October 2021 through January 2022. Survey content consisted of demographics and the General Self-efficacy Scale, which measures the individual’s perceived ability to cope and execute tasks when faced with hardship or adversity. Sample size was 105.

Results

Results included a high perception of self-efficacy of the clinical nurse specialist working during the pandemic, no statistical significance in practice focus, and a statistically significant difference in the scores of self-efficacy for participants with previous infectious disease experience compared with those without experience.

Conclusions

Clinical nurse specialists with previous infectious disease experience can guide policy, be utilized in multifaceted roles to support future infectious disease outbreaks, and develop training to prepare and support clinicians during crises such as pandemics.