bluuebunny/crossref_metadata_2025 huggingface dataset:
414 Baseline serum biomarkers do not predict dupilumab treatment response in adults with moderate-to-severe atopic dermatitis
Authors: Weidinger Stephan , Beck Lisa A , de Bruin-Weller Marjolein S   , Thyssen Jacob P , Kabashima Kenji  , Guttman-Yassky Emma , Akdis Cezmi A , Chen Zhen , Levit Noah A , Bastian Mike
Published: June 2023

Previous analyses based on short-term, phase 2 studies reported that baseline biomarkers do not correlate with clinical outcomes following dupilumab treatment in patients with atopic dermatitis (AD). This new analysis based on 16-week, phase 3 studies reports whether pretreatment levels of common serum biomarkers can predict treatment response to dupilumab in adults with moderate-to-severe AD. LIBERTY AD SOLO 1 and 2 (NCT02277743 and NCT02277769), two randomized, double-blind studies, included patients ≥18 years-old with moderate-to-severe AD treated with dupilumab 300 mg every 2 weeks or placebo for 16 weeks. Correlation between change in Eczema Area and Severity Index (EASI) and log of baseline IgE, CC chemokine ligand 17 [CCL17; previously referred to as thymus and activation-regulated chemokine (TARC)] and lactate dehydrogenase (LDH) at baseline was assessed using Spearman’s correlation coefficient (ρ). At Week 16, change in EASI showed little correlation with baseline total IgE [Spearman’s correlation coefficient (ρ) = –0.14, n = 370 for dupilumab; ρ = –0.03, n = 202 for placebo], baseline CCL17 (ρ = –0.28, n = 369 for dupilumab; ρ = –0.05, n = 201 for placebo) or baseline LDH (ρ = –0.30, n = 370 for dupilumab; ρ = –0.08, n = 202 for placebo). Overall safety was consistent with the known dupilumab safety profile. Baseline levels of total IgE, CCL17 and LDH do not predict treatment response to dupilumab, as measured by EASI, in adults with moderate-to-severe AD.
437 Treatment-emergent adverse events in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis treated with dupilumab in an open-label extension clinical trial
Authors: Paller Amy S , Siegfried Elaine C , Sidbury Robert  , Lockshin Benjamin , Cork Michael  , Pinter Andreas , Xiao Jing , Khokhar Faisal A , Bansal Ashish , Prescilla Randy 
Published: June 2023

Atopic dermatitis (AD) is a chronic systemic inflammatory disease requiring long-term management. However, availability of long-term AD treatments with an acceptable risk-benefit profile is limited in pediatric patients. This ongoing phase 3 open-label extension (OLE; NCT02612454) enrolled patients aged 6 months to 17 years with moderate-to-severe AD. Patients were treated with dupilumab (weight-based dosing): 200 mg every 4 weeks (q4w; 5–14 kg), 300 mg q4w (15–29 kg) and 200 mg q2w (30–59 kg). Here we report safety data (cutoff date July 31, 2021) for 180 patients aged 6 months to 5 years who enrolled in the OLE. Of the 180 patients reported, 122 (67.8%) completed up to 16 weeks of the study, 30 (16.7%) up to Week 52 and 15 (8.3%) up to Week 156. A total of 167 (92.8%) patients were continuing treatment at the time of data cutoff. At baseline, the mean (SD) age was 3.9 (1.3) years. One hundred and nine (60.6%) patients reported treatment-emergent adverse events (TEAEs); the most common were nasopharyngitis (12.8%), upper respiratory tract infection (11.7%) and pyrexia (11.7%). One (0.6%) patient had a treatment-related severe TEAE (urticaria) that led to study drug discontinuation. Two (1.1%) patients had serious TEAEs (anaphylactic reaction and pneumonia mycoplasmal) of severe and moderate intensity, respectively. Both serious TEAEs were unrelated to treatment. Long-term safety of dupilumab in this pediatric population was generally consistent with the known dupilumab safety profile in adults and older pediatric patients.
440 Prevalence and burden of rhinoconjunctivitis in atopic dermatitis patients: a cross-sectional study
Authors: Betaharon Isaac , Silverberg Jonathan I
Published: June 2023

Allergic rhinoconjuncitivitis can be highly symptomatic and burdensome and complicates the management of eyelid and facial dermatitis in persons with atopic dermatitis (AD). However, little is known about the prevalence, burden and predictors of allergic rhinoconjunctivitis symptoms in patients with AD, particularly among adults. This study aims to determine the prevalence and predictors of allergic rhinoconjunctivitis severity in patients with AD. A cross-sectional, dermatology practice-based study was performed at an urban academic medical center (n = 507). Atopic dermatitis severity was assessed by investigator-assessed Eczema Area and Severity Index (EASI), body surface area (BSA), investigator’s global assessment (IGA), objective-SCORing AD and patient-reported Global Assessment (PtGA). Impact of allergic rhinoconjunctivitis symptoms was assessed by Rhinoconjunctivitis Quality of Life Questionnaire. The cohort included children (<18 years; n = 36, 7.1%), young adults (18–49 years; n = 281, 55.4%) and older adults (≥50 years; n = 190, 37.5%), males (n = 219, 43.2%) and females (n = 288, 56.8%), Hispanics (n = 43, 8.5%), Blacks (n = 50, 9.9%), White non-Hispanics (n = 349, 68.8%), Asians (n = 51, 10.1%) and multiracial/other race (n = 14, 2.8%); 413 (81.5%) had private insurance. Overall, 246 (48.5%) reported a history of hay fever, and 15 (3.0%) and 416 (82.1%) of patients with AD reported having trouble with one or multiple rhinoconjunctivitis symptoms in the past 2 weeks; 30 (5.9%) and 365 (72.0%) of patients with AD had quite a bit or extreme trouble with one or multiple rhinoconjunctivitis symptoms, respectively. More severe AD overall (EASI, BSA, IGA and PtGA), as well as more severe facial dermatitis, flexural eczema and xerosis were associated with worse rhinoconjunctivitis symptoms, whereas, race, gender and presence of nummular dermatitis were generally not associated with rhinoconjunctivitis symptom severity. Quite a bit or extreme trouble from one or more rhinoconjunctivitis symptoms was reported in 39 (56.5%) patients with clear/almost clear, 85 (74.6%) mild, 135 (82.8%) moderate and 106 (84.8%) severe PtGA scores. In multivariable ordinal logistic regression models that controlled for demographics, AD severity was significantly associated with higher odds of a wide range of nasal and ocular symptoms, as well as rhinoconjunctivitis symptoms negatively impacting daily activities, causing sleep and practical problems, and negative emotions. Allergic rhinoconjunctivitis symptoms occurred in more than 4 out of 5 patients with AD overall, and almost 90% of patients with severe AD. Allergic rhinoconjunctivitis was more common in those with more severe AD, and particularly those with more severe facial dermatitis, flexural eczema and xerosis. Rhinconjunctivitis symptoms negatively impact the lives of patients with AD and warrant appropriate screening and management in clinical practice.
Report on Sino–Indian Border Disputes: International Law and International Relations Perspectives
Authors: Lone Fozia Nazir
Published: June 2023

This article is based on remarks and presentations made at two symposiums—namely, the International Online Symposium on Sino–Indian Border Disputes: A Dialogue between International Law and International Relations, and the Second International Online Symposium on The Peaceful Settlement of the Sino–Indian Boundary Dispute: A Pragmatic Multidisciplinary Framework (中國法與比較法研究中心第二次國際在線研討會—[和平解決中印邊界爭端：務實的多學科框架]). These were hosted by the City University of Hong Kong’s School of Law: Centre for Chinese and Comparative Law, in collaboration with the Public Law and Human Rights Forum, on 4 March 2021 and 9 December 2021 respectively. The article reflects on the nature of the Sino–Indian Border Dispute (SIBD) and provides transitory remarks on concepts that promote either its settlement or the mitigation/maintenance of its status quo. Based on the range of issues and variables raised by discussants regarding challenges and opportunities of the SIBD, articulated from the perspectives of international law and international relations, history, political science, geography, and more, this article emphasizes a multidisciplinary approach to SIBD settlement with a context-specific assessment of each sector.
Intraspecific variation among Chinook Salmon populations indicates physiological adaptation to local environmental conditions
Authors: Zillig Kenneth W , FitzGerald Alyssa M , Lusardi Robert A , Cocherell Dennis E , Fangue Nann A
Published: June 2023

Understanding interpopulation variation is important to predicting species responses to climate change. Recent research has revealed interpopulation variation among several species of Pacific salmonids; however, the environmental drivers of population differences remain elusive. We tested for local adaptation and countergradient variation by assessing interpopulation variation among six populations of fall-run Chinook Salmon from the western United States. Juvenile fish were reared at three temperatures (11, 16 and 20°C), and five physiological metrics were measured (routine and maximum metabolic rate, aerobic scope, growth rate and critical thermal maximum). We then tested associations between these physiological metrics and 15 environmental characteristics (e.g. rearing temperature, latitude, migration distance, etc.). Statistical associations between the five physiological metrics and 15 environmental characteristics supported our hypotheses of local adaptation. Notably, latitude was a poor predictor of population physiology. Instead, our results demonstrate that populations from warmer habitats exhibit higher thermal tolerance (i.e. critical thermal maxima), faster growth when warm acclimated and greater aerobic capacity at high temperatures. Additionally, populations with longer migrations exhibit higher metabolic capacity. However, overall metabolic capacity declined with warm acclimation, indicating that future climate change may reduce metabolic capacity, negatively affecting long-migrating populations. Linking physiological traits to environmental characteristics enables flexible, population-specific management of disparate populations in response to local conditions.
Integrated global analysis in spider flowers illuminates features underlying the evolution and maintenance of C4 photosynthesis
Authors: Zhao Wei , Li Jun , Sun Xingchao , Zheng Qiwei , Liu Jing , Hua Wei , Liu Jun
Published: June 2023

The carbon concentrating mechanism—C4 photosynthesis—represents a classic example of convergent evolution, but how this important trait originated and evolved remains largely enigmatic. The spider flower Gynandropsis gynandra is a valuable leafy vegetable crop and medicinal plant that has also been recognized as a C4 model species. Here we present a high-quality chromosome-scale annotated genome assembly of G. gynandra through a combination of Oxford Nanopore Technology (ONT), HiFi and Hi-C technology. The 17 super-scaffolds cover 98.66% of the estimated genome (997.61 Mb), with a contig N50 of 11.43 Mb and a scaffold N50 of 51.02 Mb. Repetitive elements occupy up to 71.91% of its genome, and over half are long terminal repeat retrotransposons (LTR-RTs) derived from recent bursts, contributing to genome size expansion. Strikingly, LTR-RT explosion also played a critical role in C4 evolution by altering expression features of photosynthesis-associated genes via preferential insertion in promoters. Integrated multiomics analyses of G. gynandra and the ornamental horticulture C3 relative Tarenaya hassleriana reveal that species-specific whole-genome duplication, gene family expansion, recent LTR–RT amplification, and more recent tandem duplication events have all facilitated the evolution of C4 photosynthesis, revealing uniqueness of C4 evolution in the Cleome genus. Moreover, high leaf vein density and heat stress resilience are associated with shifted gene expression patterns. The mode of C3-to-C4 transition found here yields new insights into evolutionary convergence of a complex plant trait. The availability of this reference-grade genomic resource makes G. gynandra an ideal model system facilitating efforts toward C4-aimed crop engineering.
Methods and Measures for Investigating Microscale Motility
Authors: Bondoc-Naumovitz Karen Grace , Laeverenz-Schlogelhofer Hannah , Poon Rebecca N , Boggon Alexander K , Bentley Samuel A , Cortese Dario , Wan Kirsty Y
Published: June 2023

Synopsis

Motility is an essential factor for an organism’s survival and diversification. With the advent of novel single-cell technologies, analytical frameworks, and theoretical methods, we can begin to probe the complex lives of microscopic motile organisms and answer the intertwining biological and physical questions of how these diverse lifeforms navigate their surroundings. Herein, we summarize the main mechanisms of microscale motility and give an overview of different experimental, analytical, and mathematical methods used to study them across different scales encompassing the molecular-, individual-, to population-level. We identify transferable techniques, pressing challenges, and future directions in the field. This review can serve as a starting point for researchers who are interested in exploring and quantifying the movements of organisms in the microscale world.
Postrelease assessment of Oobius agrili (Hymenoptera: Encyrtidae) establishment and persistence in Michigan and the Northeastern United States
Authors: Quinn Nicole F , Petrice Toby R , Schmude Jonathan M , Poland Therese M , Bauer Leah S , Rutlege Claire E , Van Driesche Roy G , Elkinton Joseph S , Duan Jian J
Published: June 2023

The emerald ash borer (EAB), Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), is an invasive woodboring pest of ash trees (Fraxinus sp.) in North America. Among the Asiatic parasitoids being released for the management of EAB in North America, Oobius agrili Zhang and Huang (Hymenoptera: Encyrtidae) is the only EAB egg parasitoid. To date, more than 2.5 million O. agrili have been released in North America; however, few studies have examined its success as a biological control agent of EAB. We conducted studies to assess O. agrili establishment, persistence, spread, and EAB egg parasitism rates in Michigan at the earliest release sites (2007–2010), as well as at more recent release sites (2015–2016) in 3 Northeastern United States (Connecticut, Massachusetts, New York). In both regions, we documented successful O. agrili establishment at all but one release site. In Michigan, O. agrili has persisted at release sites for over a decade and spread to all control sites located 0.6–3.8 km from release sites. Overall, EAB egg parasitism ranged from 1.5% to 51.2% (mean of 21.4%) during 2016–2020 in Michigan and from 2.6% to 29.2% (mean of 16.1%) during 2018–2020 in the Northeastern states. Future research efforts should focus on factors affecting the spatiotemporal variation in EAB egg parasitism rates by O. agrili, as well as its potential range in North America.
Induction of resistance, enzyme activity, and phytochemicals in canola plants treated with abscisic acid elevated based on nutrient availability: a case study on Brevicoryne brassicae L. (Hemiptera: Aphididae)
Authors: Dehghan Azita , Rounagh-Ardakani Hamed , Mohammadzadeh Ali , Mohammadzadeh Mohammad , Mohammadzadeh Mozhgan , Borzoui Ehsan
Published: June 2023

The cabbage aphid, Brevicoryne brassicae L. (Hemiptera: Aphididae), is one of the important pests of cruciferous plants throughout the world including Iran. In the present study, we grew cultivated canola plants under different fertilizers or distilled water and sprayed them with 100 µM abscisic acid (ABA) or a control solution (NaOH dissolved in water) to study (i) the antibiosis parameters of B. brassicae on these plants; (ii) the antixenosis of B. brassicae adults on these plants; (iii) the plant’s peroxidase (POD), polyphenol oxidase (PPO), and phenylalanine ammonia-lyase (PAL) activity; and (iv) the plant’s total phenolic and glucosinolate content. The results of antibiosis experiments showed that ABA and fertilizers have a profound and negative effect on the performance of B. brassicae. In the antixenosis experiment, control plants attracted a significantly higher number of adult females in comparison to treated plants. Also, B. brassicae had lower performance and preference when they were reared on the ABA-treated fertilized plants with higher levels of phenolic and glucosinolate content. These results prompted us to hypothesize that fertilizers enable canola plants to trigger a higher level of secondary metabolites. Our findings reveal that the type and level of nutrient availability may have different impacts on how the plant regulates its defense mechanisms.
The Book of the Dead in the Third Intermediate Period
Authors: Lenzo Giuseppina
Published: June 2023

This essay presents the different kinds of Books of the Dead in use during the Third Intermediate Period. Most of the Books of the Dead are from the Theban area, belonging to the clergy of Karnak, and are on papyri, but some spells were also engraved in the tombs of Lower Egypt, such as in Tanis. At the beginning of the Twenty-first Dynasty, Book of the Dead papyri in hieroglyphs generally follow the Ramesside tradition, only they are a little bit shorter and show some innovations. At the same time, other kinds of papyri appear in both hieroglyphs and hieratic, with many innovations. While hieratic became the most frequently used writing on papyri after the pontificate of Pinedjem II, hieroglyphs for the Book of the Dead do not seem to have been used after the Twenty-first Dynasty.
The “Dark Matter” of Stratification Research
Authors: Jackson Michelle , Moullin Sophie
Published: June 2023

For many decades, it has been clear that noncognitive characteristics play an important role in processes of stratification and mobility, yet it has only been recently that the study of noncognitive characteristics has coalesced into a distinctive subfield of stratification research. Many social scientists are unfamiliar with standard measures of noncognitive characteristics and thus have not considered how basic models of the stratification and mobility process might be adapted to take account of noncognitive characteristics. This chapter provides stratification researchers with a clear introduction to noncognitive characteristics, covering measurement, theory, and the existing empirical consensus with respect to educational and occupational attainment, earnings, and mobility. It discusses outstanding theoretical and empirical challenges within the field and calls for a renewed focus on theory development in future studies of noncognitive characteristics and socioeconomic attainment.
Modelling Drift and Selection in Cultural Evolution
Authors: Bentley R. Alexander , Carrignon Simon , Ruck Damian J.
Published: June 2023

A discussion of drift versus selection in cultural evolution lies in the context of a deep investigation on the nature of cultural evolution, which can be found in the rest of this volume. Ultimately, this chapter expresses these concepts as a two-dimensional space that parameterizes a unified model of human decision-making. One dimension of this space highlights individual versus social learning, the other captures selection versus drift. At the centre of this framework sits the neutral model of cultural drift, which it is suggested here is a good null model to use for identifying cultural selection, especially in contemporary cultural contexts such as social media and whatever lies beyond. The key to any analysis using drift as a null model is to identify metrics that can be compared between models and the data, increasingly by using highly computational methods of inference to estimate the best parameter combination in replicating those metrics.
The Role of Ritual in the Evolution of Social Complexity
Authors: Whitehouse Harvey
Published: June 2023

Cultural rituals—from simple forms of greeting, leave-taking, and dining etiquette to much more elaborate ceremonies memorializing the past, appealing to supernatural beings and forces, or marking key life transitions such as weddings and funerals—have been documented in all human societies. Certain aspects of ritual are also early developing and species specific, prompting the question whether such behaviour constitutes an evolved adaptation. Moreover, rituals appear to have contributed to the rise and spread of more complex and larger-scale social formations. This chapter considers the role of ritual in the evolution of social complexity through the lens of cultural group selection theory. Seven mechanisms underlying cultural inheritance systems are considered: high-fidelity copying; conformism bias; identity markers; coordination payoffs; policing; one-to-many transmission; institutional complexity. Drawing on theories and evidence from social anthropology, history, experimental psychology, and cross-cultural surveys, it is argued that rituals have contributed to the operation of all seven mechanism in the evolution of social complexity.
Language Phylogenies
Authors: Greenhill Simon J.
Published: June 2023

Recent years have seen Bayesian phylogenetic methods from evolutionary biology applied to questions about language evolution in two major contexts. First, language phylogenies are now routinely used to make inferences and test hypotheses about human prehistory. Second, language phylogenies provide a solid backbone to test hypotheses about how aspects of language and culture have evolved in three key ways: by revealing the evolutionary dynamics, by modelling the trait history, and testing coevolutionary hypotheses. This chapter surveys this literature, presents some case studies that highlight how these tools have been and continue to be useful, and discusses some shortcomings and open problems.
Arabidopsis PLANT U-BOX44 down-regulates osmotic stress signaling by mediating Ca2+-DEPENDENT PROTEIN KINASE4 degradation
Authors: Fan Wei , Liao Xiliang , Tan Yanqiu , Wang Xiruo , Schroeder Julian I , Li Zixing
Published: June 2023

Calcium (Ca2+)-dependent protein kinases (CPKs) are essential regulators of plant responses to diverse environmental stressors, including osmotic stress. CPKs are activated by an increase in intracellular Ca2+ levels triggered by osmotic stress. However, how the levels of active CPK protein are dynamically and precisely regulated has yet to be determined. Here, we demonstrate that NaCl/mannitol-induced osmotic stress promoted the accumulation of CPK4 protein by disrupting its 26S proteasome-mediated CPK4 degradation in Arabidopsis (Arabidopsis thaliana). We isolated PLANT U-BOX44 (PUB44), a U-box type E3 ubiquitin ligase that ubiquitinates CPK4 and triggers its degradation. A calcium-free or kinase-inactive CPK4 variant was preferentially degraded compared to the Ca2+-bound active form of CPK4. Furthermore, PUB44 exhibited a CPK4-dependent negative role in the response of plants to osmotic stress. Osmotic stress induced the accumulation of CPK4 protein by inhibiting PUB44-mediated CPK4 degradation. The present findings reveal a mechanism for regulating CPK protein levels and establish the relevance of PUB44-dependent CPK4 regulation in modulating plant osmotic stress responses, providing insights into osmotic stress signal transduction mechanisms.
Default egocentrism: an MVPA approach to overlap in own and others’ socio-political attitudes
Authors: Welborn B Locke , Dieffenbach Macrina C , Lieberman Matthew D
Published: June 2023

Understanding the socio-political attitudes of other people is a crucial skill, yet the neural mechanisms supporting this capacity remain understudied. This study used multivariate pattern analysis to examine patterns of activity in the default mode network (DMN) while participants assessed their own attitudes and the attitudes of other people. Classification analyses indicated that common patterns in DMN regions encode both own and others’ support across a variety of contemporary socio-political issues. Moreover, cross-classification analyses demonstrated that a common coding of attitudes is implemented at a neural level. This shared informational content was associated with a greater perceived overlap between own attitude positions and those of others (i.e. attitudinal projection), such that higher cross-classification accuracy corresponded with greater attitudinal projection. This study thus identifies a possible neural basis for egocentric biases in the social perception of individual and group attitudes and provides additional evidence for self/other overlap in mentalizing.
Necessary Products for the Prevention and Treatment of Pressure Injuries: Lessons Learned That Translate Beyond the COVID-19 Pandemic
Authors: Delmore Barbara , Deppisch Michelle , Cox Jill , Newton David , Gillespie Carroll , Todd Jackie , Sonenblum Sharon Eve
Published: June 2023

OBJECTIVE

To identify the challenges encountered in obtaining the required support surfaces and products to meet pressure injury (PrI) prevention and treatment needs during COVID-19.

METHODS

The authors used SurveyMonkey to gather data on healthcare perceptions and the challenges experienced regarding specific product categories deemed necessary for PrI prevention and treatment in US acute care settings during the pandemic. They created three anonymous surveys for the target populations of supply chain personnel and healthcare workers. The surveys addressed healthcare workers’ perceptions, product requests, and the ability to fulfill product requests and meet facility protocols without substitution in the categories of support surfaces and skin and wound care supplies.

RESULTS

Respondents answered one of the three surveys for a total sample of 174 respondents. Despite specific instructions, nurses responded to the surveys designed for supply chain personnel. Their responses and comments were interesting and capture their perspectives and insights. Three themes emerged from the responses and general comments: (1) expectations differed between supply chain staff and nurses for what was required for PrI prevention and treatment; (2) inappropriate substitution with or without proper staff education occurred; and (3) preparedness.

CONCLUSIONS

It is important to identify experiences and challenges in the acquisition and availability of appropriate equipment and products for PrI prevention and treatment. To foster ideal PrI prevention and treatment outcomes, a proactive approach is required to face daily issues or the next crisis.
Challenges in treating juvenile idiopathic arthritis
Authors: Twilt Marinka , Stoustrup Peter , Rumsey Dax
Published: June 2023

Purpose of review

Juvenile idiopathic arthritis (JIA) diagnosis and classification is currently still based on clinical presentation and general laboratory tests. Some joints such as the temporomandibular joint (TMJ) and sacroiliac (SI) are hard to assess and define as actively inflamed based on clinical examination. This review addresses these difficult to assess joints and provides the latest evidence for diagnosis and treatment.

Recent findings

Recommendations on clinical examination and radiological examination are available. Recent 2021 ACR recommendations were made for TMJ arthritis and in 2019 for sacroiliitis.

New evidence to guide clinical suspicion and need for further investigations are available for these hard to assess joints. These guidelines will help healthcare providers in diagnosis and treatment assessment.
Short-term outcomes of an enhanced recovery after surgery pathway for children with congenital scoliosis undergoing posterior spinal fusion: a case–control study of 70 patients
Authors: Zhang Hanwen , Liu Haonan , Zhang Xuejun , Zhao Mengqi , Guo Dong , Bai Yunsong , Qi Xinyu , Shi Haixia , Li Duoyi
Published: June 2023

Increasing evidence demonstrates the advantages of an enhanced recovery after surgery (ERAS) protocol; however, few studies have evaluated ERAS in pediatric patients. This study aimed to evaluate the effect of ERAS in pediatric patients with congenital scoliosis. Seventy pediatric patients with congenital scoliosis underwent posterior hemivertebra resection and fusion with pedicle screws and were prospectively randomly assigned to the ERAS group (n = 35) and control group (n = 35). ERAS management comprised 15 elements including a shortened fasting time, optimized anesthesia protocol, and multimodal analgesia. The control group received traditional perioperative management. Clinical outcome was evaluated by hospital stay, surgery-related indicators, diet, pain scores, laboratory tests, and complications. The surgical outcome showed a similar correction rate in the ERAS group (84.0%) and control group (89.0%; P = 0.471). The mean fasting time was significantly shorter in the ERAS group than in the control group. Compared with the control group, the ERAS group had significantly shorter mean times to postoperative hospital stay, first anal exhaust and defecation, significantly lower mean pain scores in the first 2 days postoperatively (P < 0.05), and a significantly lower mean interleukin-6 concentration on postoperative day 1 (P < 0.001). The incidence of complications was similar in the ERAS group and control group (P > 0.05). The ERAS protocol is effective and safe for pediatric patients with congenital spinal deformity and may significantly improve the treatment efficacy compared with traditional perioperative management methods.

Levels of Evidence: III.
Mastery and Stress in Patients with Advanced or Recurrent Colorectal Cancer During Treatment: A Multicenter Cross-sectional Study
Authors: Aoki Miwa , Yamamoto Sena , Tatsumi Yukiko , Hatakeyama Akiko , Minamiguchi Yoko , Toki Masayo , Takao Ayumi , Fujikawa Naomi , Asano Kouta , Arao Harue
Published: June 2023

Background:

Mastery is a human response of gaining competence in dealing with stress and can be applied to understanding the psychological state of patients with advanced or recurrent colorectal cancer (CRC).

Objective:

To identify mastery in patients with advanced or recurrent CRC undergoing chemotherapy and examine associations between mastery and the patients’ sociodemographic characteristics, social support, and support from clinical staff.

Methods:

A self-administered survey was conducted among patients with advanced or recurrent CRC receiving outpatient chemotherapy. Participants completed the Mastery of Stress Instrument, the Multidimensional Scale of Perceived Social Support, support from clinical staff, and sociodemographic characteristics.

Results:

Of 76 participants, 77.6% had a stress score of ≥58 points, indicating a stress status. They achieved, in descending order, acceptance, certainty, change, and growth among mastery processes. Social support was significantly associated with mastery and all its components, and support from clinical staff was significantly associated with mastery and certainty.

Conclusions:

Most participants reported a high level of stress, indicating that they need support to deal with stress from a mastery perspective.

Implications for Practice:

Nurses should assess the stress levels of patients with advanced or recurrent CRC and provide care based on mastery to help patients come to terms with cancer-related stress. Providing emotional and social support is necessary to promote positive change and growth.

Foundational:

This study framed the need for nursing care for stressed patients in terms of their mastery of advanced or recurrent CRC-specific stress. Social support and clinical staff support are essential for achieving such mastery.
Within-city spatial variations in long-term average outdoor oxidant gas concentrations and cardiovascular mortality: Effect modification by oxidative potential in the Canadian Census Health and Environment Cohort
Authors: Ripley Susannah , Gao Dong , Pollitt Krystal J. Godri , Lakey Pascale S. J. , Shiraiwa Manabu , Hatzopoulou Marianne , Weichenthal Scott
Published: June 2023

Background:

Health effects of oxidant gases may be enhanced by components of particulate air pollution that contribute to oxidative stress. Our aim was to examine if within-city spatial variations in the oxidative potential of outdoor fine particulate air pollution (PM2.5) modify relationships between oxidant gases and cardiovascular mortality.

Methods:

We conducted a retrospective cohort study of participants in the Canadian Census Health and Environment Cohort who lived in Toronto or Montreal, Canada, from 2002 to 2015. Cox proportional hazards models were used to estimate associations between outdoor concentrations of oxidant gases (O
x
, a redox-weighted average of nitrogen dioxide and ozone) and cardiovascular deaths. Analyses were performed across strata of two measures of PM2.5 oxidative potential and reactive oxygen species concentrations (ROS) adjusting for relevant confounding factors.

Results:

PM2.5 mass concentration showed little within-city variability, but PM2.5 oxidative potential and ROS were more variable. Spatial variations in outdoor O
x
were associated with an increased risk of cardiovascular mortality [HR per 5 ppb = 1.028, 95% confidence interval (CI): 1.001, 1.055]. The effect of O
x
on cardiovascular mortality was stronger above the median of each measure of PM2.5 oxidative potential and ROS (e.g., above the median of glutathione-based oxidative potential: HR = 1.045, 95% CI: 1.009, 1.081; below median: HR = 1.000, 95% CI: 0.960, 1.043).

Conclusion:

Within-city spatial variations in PM2.5 oxidative potential may modify long-term cardiovascular health impacts of O
x
. Regions with elevated O
x
and PM2.5 oxidative potential may be priority areas for interventions to decrease the population health impacts of outdoor air pollution.
Global blood pressure screening during the COVID-19 pandemic: results from the May Measurement Month 2021 campaign
Authors: Beaney Thomas , Wang Wei , Schlaich Markus P. , Schutte Aletta E. , Stergiou George S. , Alcocer Luis , Alsaid Jafar , Diaz Alejandro Bimbo , Hernandez-Hernandez Rafael , Ishaq Mohammad , Jozwiak Jacek , Khan Nadia , Kiru Gaia , McCardle Harsha , Odili Augustine Nonso , Pyun Wook Bum , Romero Cesar A. , Wang Jiguang , Poulter Neil R.
Published: June 2023

Background:

Raised blood pressure (BP) remains the biggest risk factor contributing to the global burden of disease and mortality, despite the COVID-19 pandemic. May Measurement Month (MMM), an annual global screening campaign aims to highlight the importance of BP measurement by evaluating global awareness, treatment and control rates among adults with hypertension. In 2021, we assessed the global burden of these rates during the COVID-19 pandemic.

Methods:

Screening sites were set up in 54 countries between May and November 2021 and screenees were recruited by convenience sampling. Three sitting BPs were measured, and a questionnaire completed including demographic, lifestyle and clinical data. Hypertension was defined as a systolic BP at least 140 mmHg and/or a diastolic BP at least 90 mmHg (using the mean of the second and third readings) or taking antihypertensive medication. Multiple imputation was used to impute the average BP when readings were missing.

Results:

Of the 642 057 screenees, 225 882 (35.2%) were classified as hypertensive, of whom 56.8% were aware, and 50.3% were on antihypertensive medication. Of those on treatment, 53.9% had controlled BP (<140/90 mmHg). Awareness, treatment and control rates were lower than those reported in MMM campaigns before the COVID-19 pandemic. Minimal changes were apparent among those testing positive for, or being vaccinated against COVID-19. Of those on antihypertensive medication, 94.7% reported no change in their treatment because of the COVID-19 pandemic.

Conclusion:

The high yield of untreated or inadequately treated hypertension in MMM 2021 confirms the need for systematic BP screening where it does not currently exist.
Association of oral montelukast with reduced odds of developing exudative age-related macular degeneration
Authors: Matsumiya Wataru , Karaca Irmak , Pham Brandon Huy , Akhavanrezayat Amir , Uludag Gunay , Yasar Cigdem , Ghoraba Hashem , Mobasserian Azadeh , Regenold Jonathan , Halim Muhammad Sohail , Sepah Yasir J. , Do Diana V. , Chong Victor , Nguyen Quan Dong
Published: June 2023

Purpose:

This study was conducted to evaluate the association of oral montelukast, selective antagonism for cysteinyl leukotriene receptor 1, with reduced odds of exudative age-related macular degeneration (exAMD) development.

Methods:

This case-control study was conducted using Institutional Cohort Finder tool, and included 1913 patients with exAMD (ICD: H35.32 and 362.52) and 1913 age- and gender-matched control subjects without exAMD. Sub-analysis among 1913 exAMD and 324 non-exudative AMD was also conducted.

Results:

A total of 47 (2.5%) exAMD cases were identified to have a history of oral montelukast use prior to exAMD diagnosis, compared to 84 (4.4%) controls. Montelukast usage was significantly associated with reduced odds of exAMD in the multivariable analysis (adjusted OR: 0.50, 95% CI: 0.31 – 0.80) as well as NSAID usage (adjusted OR: 0.69). Caucasian race, history of smoking, non-exudative macular degeneration in either eye were also found to have significant relationship with increased odds of exAMD. In the sub-analysis, montelukast usage showed significant association with reduced odds of developing exAMD from non-exudative AMD (adjusted OR: 0.53 95% CI: 0.29 – 0.97) as well as the presence of atopic disease (adjusted OR: 0.60).

Conclusion:

The study results suggested that oral montelukast is linked to reduced odds of exAMD development.
Cadaveric Evaluation of the Canalicular-Lacrimal Sac-Mucosal Folds and Clinical Implications
Authors: Lim Blanche Xiao Hong , Gungab Alexander Gerard Nino L. , Boniao Emmanuel Lee Ong , Sundar Gangadhara , Ali Mohammad Javed
Published: June 2023

Purpose:

The purpose is to study the anatomical variations of the characteristic mucosal folds at the canalicular-lacrimal sac junction and their potential clinical implications.

Methods:

Twelve lacrimal drainage systems of six fresh frozen Caucasian cadavers were studied to assess the openings of the common canaliculus into the lacrimal sac. A standard endoscopic dacryocystorhinostomy was performed until complete lacrimal sac marsupialization and reflection of the flaps. All specimens were subjected to clinical assessment of lacrimal patency via irrigation. A high-definition nasal endoscopy assessed the internal common opening and the mucosal folds in its close vicinity. Probing at the internal common opening was performed to aid in the assessment of the folds. Videography and photo documentation was performed.

Results:

All 12 specimens had a single common canalicular opening. Ten of the 12 specimens (83.3%) were noted to have canalicular/lacrimal sac-mucosal folds (CLS-MF). Anatomical variations were noted across these 10 specimens and included inferior 180° (n = 6), anterior 270° (n = 2), posterior 180° (n = 1), and 360° CLS-MF (n = 1). Cases were randomly chosen to demonstrate the clinical implications of misinterpreting them as canalicular obstructions or the potential to cause an inadvertent false passage.

Conclusion:

The inferior 180° was the most common CLS-MF noted in the cadaveric study. It is helpful for clinicians to recognize the prominent CLS-MF and their clinical implications intraoperatively. Further fundamental work is needed to characterize the anatomy and the possible physiological role of CLS-MFs.
Characteristics of Retrobulbar Hemorrhage Presentation in the Emergency Department
Authors: Tram Justin K. , Pauze Denis R. , Wladis Edward J.
Published: June 2023

Purpose:

To describe demographic and clinical features of emergency department patients presenting with fracture-associated (FA) or fracture-independent retrobulbar hemorrhage (RBH).

Methods:

The Nationwide Emergency Department Sample database 2018 and 2019 was used to compare demographic and clinical features of patients with fracture-independent RBH and FA RBH.

Results:

A total of 444 fracture-independent and 359 FA RBH patients were identified. Demographics such as age distribution, gender, and payer type differed significantly, with young (21–44 years), privately insured males more likely to develop FA RBH and the elderly (65+ years) more likely to develop fracture-independent RBH. Prevalence of hypertension and anticoagulation did not differ, but substance use and ocular-related injuries were more prevalent in the FA RBH.

Conclusion:

Presentations of RBH differ in demographic and clinical features. Further research is needed to explore trends and guide decision-making in the emergency department.
Optimizing liver transplant prioritization for hepatocellular carcinoma through risk stratification
Authors: Norman Joshua , Mehta Neil , Kwong Allison
Published: June 2023

Purpose of review

In the United States, candidates with hepatocellular carcinoma (HCC) meeting standardized qualifying criteria receive similar priority on the liver transplant waiting list through Model for End-Stage Liver Disease exception points, without consideration of the dropout risk or relative expected benefit from liver transplantation. A more nuanced allocation scheme for HCC is needed to better represent the individual urgency for liver transplant and optimize organ utility. In this review, we discuss the development of HCC risk prediction models for practical use in liver allocation.

Recent findings

HCC is a heterogenous disease that requires improved risk stratification for patients who fall within current transplant eligibility criteria. Several models have been proposed, though none have been adopted in clinical practice or liver allocation to date, due to various limitations.

Improved HCC risk stratification for liver transplant candidates is needed to more accurately represent their urgency for transplant, with continued attention to the potential impact on post-liver transplant outcomes. Plans to implement a continuous distribution model for liver allocation in the United States may provide an opportunity to re-consider a more equitable allocation scheme for patients with HCC.
Inpatient rehabilitation for acute presentations of motor functional neurological disorder (FND): A retrospective cohort study
Authors: Polich Ginger , Zalanowski Stacey , Lewis Julie Maney , Sugarman Sarah , Christopulos Kanella , Hebb Caitlin , Perez David L. , Baslet Gaston , Shah Priyanca , Herman Seth
Published: June 2023

Objective

Patients with Functional Neurological Disorder (FND) involving the motor system (e.g., functional weakness, functional gait) may acutely present to the hospital for new-onset symptoms. For some, symptoms may remain severe enough at the time of hospital discharge to qualify for an inpatient rehabilitation facility (IRF) stay.

Design

Data were extracted via retrospective chart review on FND patients (n = 22) admitted to an IRF between September 2019 and May 2022. Demographic and clinical data, including admission and discharge physical and occupational therapy measurements on the IRF-Patient Assessment Instrument (IRF-PAI), were recorded and analyzed.

Results

Symptom duration was less than one week for nearly two-thirds of the cohort. Following an approximately two-week length of stay, patients showed statistically significant changes in admission to discharge measures of self-care, transfers, ambulation, and balance. More than 95% of patients were able to be discharged home. The presence or absence of comorbid depression, anxiety, or PTSD did not impact outcomes.

Conclusions

For a subset of patients with persistent motor symptoms following an acute hospital admission for a new diagnosis of FND, a relatively short IRF stay was associated with significant clinical gains.
The structural basis of the talin–KANK1 interaction that coordinates the actin and microtubule cytoskeletons at focal adhesions
Authors: Li Xingchen , Goult Benjamin Thomas , Ballestrem Christoph , Zacharchenko Thomas
Published: June 2023

Adhesion between cells and the extracellular matrix is mediated by heterodimeric (
αβ
) integrin receptors that are intracellularly linked to the contractile actomyosin machinery. One of the proteins that control this link is talin, which organizes cytosolic signalling proteins into discrete complexes on β-integrin tails referred to as focal adhesions (FAs). The adapter protein KANK1 binds to talin in the region of FAs known as the adhesion belt. Here, we adapted a non-covalent crystallographic chaperone to resolve the talin–KANK1 complex. This structure revealed that the talin binding KN region of KANK1 contains a novel motif where a β-hairpin stabilizes the α-helical region, explaining both its specific interaction with talin R7 and high affinity. Single point mutants in KANK1 identified from the structure abolished the interaction and enabled us to examine KANK1 enrichment in the adhesion belt. Strikingly, in cells expressing a constitutively active form of vinculin that keeps the FA structure intact even in the presence of myosin inhibitors, KANK1 localizes throughout the entire FA structure even when actomyosin tension is released. We propose a model whereby actomyosin forces on talin eliminate KANK1 from talin binding in the centre of FAs while retaining it at the adhesion periphery.
Evaluation and validation of a commercial ELISA versus the in vitro toxin neutralization assay for determination of diphtheria anti-toxin in human serum
Authors: Kitamura Noriko , Endo Akira , Le Lien T. , Nguyen Trieu B. , Do Hung T. , Toizumi Michiko , Yoshida Lay-Myint , Mori Yoshio , Rose Samuel , Efstratiou Androulla , Fry Norman K. , Litt David
Published: June 2023

Introduction. Diphtheria is a potentially life-threatening infection and remains endemic in many low- and middle-income countries (LMICs). A reliable, low-cost method for serosurveys in LMICs is warranted to estimate the accurate population immunity to control diphtheria.

Hypothesis/Gap Statement. The correlation between the ELISA results against diphtheria toxoid and the gold standard diphtheria toxin neutralization test (TNT) values is poor when ELISA values are <0.1 IU ml−1, which results in inaccurate estimates of susceptibility in populations when ELISA is used for measuring antibody levels.

Aim. To explore methods to accurately predict population immunity and TNT-derived anti-toxin titres from ELISA anti-toxoid results.

Methodology. A total of 96 paired serum and dried blood spot (DBS) samples collected in Vietnam were used for comparison of TNT and ELISA. The diagnostic accuracy of ELISA measurement with reference to TNT was assessed by area under the receiver operating characteristic (ROC) curve (AUC) and other parameters. Optimal ELISA cut-off values corresponding to TNT cut-off values of 0.01 and 0.1 IU ml−1 were identified by ROC analysis. A method based on the multiple imputation approach was also applied to estimate TNT measurements in a dataset that only included ELISA results. These two approaches were then applied to ELISA results previously generated from 510 subjects in a serosurvey in Vietnam.

Results. The ELISA results on DBS samples showed a good diagnostic performance compared to TNT. The cut-off values for ELISA measurement corresponding to the TNT cut-off values of 0.01 IU ml−1 were 0.060 IU ml−1 in serum samples, and 0.044 IU ml−1 in DBS samples. When a cut-off value of 0.06 IU ml−1 was applied to the 510 subject serosurvey data, 54 % of the population were considered susceptible (<0.01 IU ml−1). The multiple imputation-based approach estimated that 35 % of the population were susceptible. These proportions were much larger than the susceptible proportion estimated by the original ELISA measurements.

Conclusion. Testing a subset of sera by TNT combined with ROC analysis or a multiple imputation approach helps to adjust ELISA thresholds or values to assess population susceptibility more accurately. DBS is an effective low-cost alternative to serum for future serological studies for diphtheria.