bluuebunny/crossref_metadata_2025 huggingface dataset:
NATO in the multi-order world
Authors: Flockhart Trine
Published: March 2024

NATO has for 75 years been a remarkably resilient organization because it has been able to change when the world changed. NATO's longevity is in large part due to a dual structure, which has enabled the alliance to oscillate between a role as a military alliance and as a community of value. The Russian invasion of Ukraine and global geopolitical shifts such as the rise of China prompted NATO to prioritize its role as a military alliance and to add a new political focus on China. However, this article demonstrates that NATO's reading of the geopolitical transformation is incomplete. NATO should recognize the new global ordering architecture as a multi-order one, which requires NATO to distinguish clearly between the ‘unbounded’ global rules-based order in which several international orders now exist and the ‘bounded’ liberal international order of which NATO is a key institution. NATO needs to develop its policies accordingly—policies governing relations within the liberal international order must be clearly anchored in liberal values and designed to defend liberal international order, while policies governing relations between international orders cannot be anchored in liberal values, but must seek rules-based cooperation in areas of shared interests.
Chinese peace and its discontents: China's peacemaking and peacekeeping in South Sudan
Authors: Patey Luke
Published: March 2024

China shows a growing commitment to peacemaking and peacekeeping overseas. Yet Chinese peace efforts have met considerable challenges across multiple conflict settings. This article seeks to understand the difficulties facing Chinese peacemaking and peacekeeping and asks how these experiences influence the future behaviour of Chinese actors towards peace and conflict issues. Previous scholarship has largely taken a state-centric perspective to explain China's engagement in peacemaking and peacekeeping. In contrast, this article harnesses an assemblage approach to reveal the diversity of Chinese actors and the significant role local actors and normative forms of power play in influencing China's broader peace efforts. In South Sudan, it finds that the political ideas advanced by warring factions and the legitimacy they placed on United Nations peacekeeping intervention, both undermined Chinese peacemaking and peacekeeping and held far-reaching effects for Chinese actors beyond the conflict. Consequently, these challenges in South Sudan pushed China's national oil company to adopt new risk management policies throughout its investments in conflict settings. The South Sudan experience also influenced China's foreign ministry by tempering its proactive approach to conflict resolution in other conflict-affected countries and to promote peacekeeper safety and support peacekeeping intelligence at the United Nations.
Pharmacokinetics, safety, and efficacy of 20% subcutaneous immunoglobulin (Ig20Gly) administered weekly or every 2 weeks in Japanese patients with primary immunodeficiency diseases: a phase 3, open-label study
Authors: Kanegane Hirokazu , Endo Akifumi , Okada Satoshi , Ohnishi Hidenori , Ishimura Masataka , Nishikomori Ryuta , Imai Kohsuke , Nonoyama Shigeaki , Muramatsu Hideki , Wada Taizo , Kuga Atsushi , Sakamoto Ko , Russo-Schwarzbaum Sharon , Chu Liang-Hui , McCoy Barbara , Li Zhaoyang , Yel Leman
Published: March 2024

This phase 3, open-label, multidose study (NCT04346108) evaluated the pharmacokinetics, safety, tolerability, and efficacy of immunoglobulin subcutaneous (human) 20% solution (Ig20Gly) administered weekly and every 2 weeks in Japanese patients with primary immunodeficiency diseases (PIDs). The study was conducted at eight study sites in Japan and enrolled patients aged ≥2 years with PIDs treated using a stable intravenous immunoglobulin dose for ≥3 months prior to the study. Patients received intravenous immunoglobulin every 3 or 4 weeks at pre-study dose (200–600 mg/kg) for 13 weeks (Epoch 1), subcutaneous Ig20Gly (50–200 mg/kg) once weekly for 24 weeks (Epoch 2), and Ig20Gly (100–400 mg/kg) every 2 weeks for 12 weeks (Epoch 3). The primary endpoint was serum total immunoglobulin G (IgG) trough levels during Epochs 2 and 3. Overall, 17 patients were enrolled (median [range] age: 24 [5–69] years; 59% male) and participated in Epochs 1 and 2; seven patients entered Epoch 3. Serum total IgG trough levels were maintained at >8 g/l: geometric means (95% confidence intervals) at the end of Epochs 2 and 3 were 8.56 (8.03–9.12) g/l and 8.39 (7.89–8.91) g/l, respectively. Related treatment-emergent adverse events were all mild in severity; the most common treatment-emergent adverse events (excluding infections) in Epochs 2 and 3 were injection site swelling (24%) and injection site erythema (18%). This is the first trial to demonstrate the efficacy and favourable safety profile of 20% subcutaneous immunoglobulin administered every 2 weeks in adult and paediatric Japanese patients with PIDs.
Gut microbiota facilitate adaptation of invasive moths to new host plants
Authors: Zhang Shouke , Song Feng , Wang Jie , Li Xiayu , Zhang Yuxin , Zhou Wenwu , Xu Letian
Published: March 2024

Gut microbiota are important in the adaptation of phytophagous insects to their plant hosts. However, the interaction between gut microbiomes and pioneering populations of invasive insects during their adaptation to new hosts, particularly in the initial phases of invasion, has been less studied. We studied the contribution of the gut microbiome to host adaptation in the globally recognized invasive pest, Hyphantria cunea, as it expands its range into southern China. The southern population of H. cunea shows effective adaptation to Metasequoia glyptostroboides and exhibits greater larval survival on Metasequoia than the original population. Genome resequencing revealed no significant differences in functions related to host adaptation between the two populations. The compatibility between southern H. cunea populations and M. glyptostroboides revealed a correlation between the abundance of several gut bacteria genera (Bacteroides, Blautia, and Coprococcus) and H. cunea survival. Transplanting the larval gut microbiome from southern to northern populations enhanced the adaptability of the latter to the previously unsuitable plant M. glyptostroboides. This research provides evidence that the gut microbiome of pioneering populations can enhance the compatibility of invasive pests to new hosts and enable more rapid adaptation to new habitats.
Patterns and mechanisms of belowground carbon responses to changes in precipitation
Authors: Chen Hongyang , Zhang Qi , Zhou Lingyan , Zhou Xuhui
Published: March 2024

It is well known that aboveground productivity usually increases with precipitation. However, how belowground carbon (C) processes respond to changes in precipitation remains elusive, although belowground net primary productivity (BNPP) represents more than one-half of NPP and soil stores the largest terrestrial C in the biosphere. This paper reviews the patterns of belowground C processes (BNPP and soil C) in response to changes in precipitation from transect studies, manipulative experiments, modeling and data integration and synthesis. The results suggest the possible existence of nonlinear patterns of BNPP and soil C in response to changes in precipitation, which is largely different from linear response for aboveground productivity. C allocation, root turnover time and species composition may be three key processes underlying mechanisms of the nonlinear responses to changes in precipitation for belowground C processes. In addition, microbial community structure and long-term ecosystem processes (e.g. mineral assemblage, soil texture, aggregate stability) may also affect patterns of belowground C processes in response to changes in precipitation. At last, we discuss implications and future perspectives for potential nonlinear responses of belowground C processes to changes in precipitation.
A systematic review and meta-analysis of sexually transmitted infections and blood-borne viruses in travellers
Authors: Shiferaw Wondimeneh , Martin Beatris Mario , Dean Judith A , Mills Deborah , Lau Colleen , Paterson David , Koh Kenneth , Eriksson Lars , Furuya-Kanamori Luis
Published: March 2024

Background

Sexually transmitted infections (STIs) and blood-borne viruses (BBVs) impose a global health and economic burden. International travellers facilitate the spread of infectious diseases, including STIs. Hence, this review assessed the prevalence/proportionate morbidity of travellers with STIs and sexually transmitted BBVs and factors associated with the infection in this population.

Methods

PubMed, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase and Cochrane Library were searched from inception of the databases until November 2022. Published analytical observational studies reporting the prevalence/proportionate morbidity of travellers with STIs and factors associated with STIs by type of traveller [i.e. tourists, business travellers, students, visiting friends or relatives (VFRs), international truck drivers, backpackers, expatriates and men who have sex with men (MSM)] were included. The selection of articles, data extraction and risk of bias assessment were conducted by two independent reviewers. Meta-analyses were conducted for each STI by clinical presentation and type of traveller.

Results

Thirty-two studies (n = 387 731 travellers) were included; 19 evaluated the proportionate morbidity of STIs among symptomatic travellers, while 13 examined the prevalence of STIs in asymptomatic travellers. The highest proportionate morbidity was found among VFRs (syphilis, 1.67%; 95% CI: 1.03–2.81%), backpackers (Chlamydia trachomatis, 6.58%; 95% CI: 5.96–7.25%) and MSM (HIV [2.50%;95% CI: 0.44–12.88%], gonorrhoea [4.17%; 95% CI: 1.1.5–13.98%], lymphogranuloma venereum [4.17%;95% CI: 1.1.5–13.98%] and HAV [20.0%; 95% CI: 14.99–26.17%]). The highest prevalence of STIs among asymptomatic were found in MSM (HIV [25.94%; 95% CI: 22.21–30.05%] and HBV [24.90%; 95% CI: 21.23–28.96%]) and backpackers (C. trachomatis, 3.92%; 95% CI: 2.72–5.32%). Short duration of the trip (<1 month), not having pre-travel consultation, travelling to Southeast Asia and being unvaccinated for HBV were identified as risk factors for STIs.

Conclusion

Strategies to prevent STIs and sexually transmitted BBVs should be discussed at pre-travel consultations, and recommendations should be prioritized in high-risk groups of travellers, such as backpackers, VFRs and MSMs. Additionally, healthcare providers should tailor recommendations for safe sex practices to individual travellers’ unique needs.
EU Directives on the internal governance of energy communities and their exclusionary effects
Authors: Hoops Björn
Published: March 2024

If already existing energy cooperatives and other citizen-led initiatives are to benefit from energy sharing and other privileges under the EU Internal Electricity Market and Renewable Energy Directives, their internal governance will have to adhere to the requirements set by these Directives. This contribution combines legal-doctrinal and empirical research on German energy communities to determine the extent to which different interpretations of the Directives respect established governance structures. It goes on to evaluate which interpretation creates the least disruptive incentives for communities to adapt their internal governance to the Directives. The contribution argues that the Directives should tolerate that energy communities pursue financial goals in addition to economic, environmental, or social benefits. It finds that the exclusion of energy companies, large enterprises, and non-local authorities from membership under the Renewable Energy Directive deters a desirable skill transfer. An exiting member should not be entitled to an immediate reimbursement, to preserve the financial viability of the community. The interpretation of autonomy and effective control should respect the indirect democracy in most communities with few active members leading the way and taking the most important decisions. Finally, the activities and size of the community should inform the interpretation of the proximity requirement.
On corrugation mode radial wavelengths of the vertical shear instability
Authors: Dang Yixuan , Cui Can , Barraza-Alfaro Marcelo
Published: March 2024

The vertical shear instability (VSI) is a promising mechanism to drive turbulence in protoplanetary discs. Numerical simulations in the literature demonstrate that the VSI non-linear saturation is predominated by the linear corrugation modes. These modes possess vertical wavelengths crucially longer than radial wavelengths. This paper aims to investigate the natural radial wavelength of corrugation modes upon VSI saturation, by a series of numerical simulations conducted in Athena++ at different grid resolutions, disc aspect ratios, and viscosity parametrized by ν. We find a sign of convergence emerges at 64 cells per gas scale height for fiducial simulations, below which a continuous reduction of wavelengths with grid resolution is observed. Synthetic ALMA molecular line observations of $^{12}\rm CO(2-1)$ are performed to inspect the observability of the corrugation modes feature, which is significantly diminished with a resolution of 32 cells per scale height or above. Flared and viscous discs exhibiting longer saturation wavelengths may mitigate the observational difficulty.
A study of Be stars in the time domain – I. Spectral data and polarimetry
Authors: Castañón Esteban Adrian , Steele Iain A , Jermak Helen E
Published: March 2024

We present the first part of a spectroscopic and polarimetric study on a sample of 58 Be stars that have been measured since 1998. The aim of the study is to understand the time-scales of disc variability, formation, and dissipation as a function of the properties (mass, luminosity, and rotational velocity) of the underlying B star. In this paper, we classified the sample based on the presence of emission or absorption of the Hα line, and the shape of the peak as single or double peak, as well as noting changes between emission and non-emission states. We find a probability of ∼0.75 per cent per year that an object in the sample will undergo such a change. We also present re-derived values of the projected rotational velocities for the sample. When we compare our polarization values with those from the literature, we find that most of the stars do not show a change in the value of the polarization angle; however, a small number show significant changes which could be attributed to either disc strength (optical depth) or geometry changes. Finally, we show how, by combining the (interstellar corrected) degree of polarization and the projected rotational velocity, we can construct an inclination angle-free parameter that includes the true equatorial velocity. Using this inclination angle-independent parameter, we show that the populations of single and double peak stars are indistinguishable, giving further evidence that Be star line profiles are essentially inclination angle driven.
Impact of the Febrile Podcast and Learning Resource as an Infectious Diseases Education Platform
Authors: Dong Sara W , Stead Wendy
Published: March 2024

Background

Febrile is an infectious diseases (ID) podcast and learning platform with the aim of providing high-quality and accessible ID content for learners. We describe the use of Febrile as a resource for learning and teaching ID as well as learner satisfaction and perceived impact on clinical practice.

Methods

The Febrile platform was launched in December 2020 and includes audio podcast episodes, infographics, and detailed online summaries of adult and pediatric ID topics. Production and contributor information is summarized. Podcast, website, and social media engagement is reported from available quantitative analytics. An online anonymous survey was conducted to assess educational impact.

Results

After 3 years of operation, Febrile has produced 90 episodes and has been downloaded >460 000 times in 196 countries, with the majority of its audience (58.9%) listening from within the United States. A total of 230 participants from 30 countries and 38 US states completed the survey, of whom 79 (34.5%) were ID fellows in training and 78 (34.2%) were ID faculty physicians. Seventy-two percent of survey respondents reported visiting the website, and 82% had seen an infographic. Enhancing core ID knowledge was the primary driver for listening. Two-thirds of respondents indicated that information learned from Febrile has changed their practice, and 50% have used Febrile as a way to teach others. Febrile also led to favorable impressions of ID for those considering ID as a career.

Conclusions

Febrile is an engaging platform for ID medical education and provides a unique resource within the global ID community.
Deletion of the sugar importer gene OsSWEET1b accelerates sugar starvation-promoted leaf senescence in rice
Authors: Chen Dan , Shi Yarui , Zhang Peng , Xie Wenya , Li Shuxin , Xiao Jinghua , Yuan Meng
Published: March 2024

Leaf senescence is a combined response of plant cells stimulated by internal and external signals. Sugars acting as signaling molecules or energy metabolites can influence the progression of leaf senescence. Both sugar starvation and accumulation can promote leaf senescence with diverse mechanisms that are reported in different species. Sugars Will Eventually be Exported Transporters (SWEETs) are proposed to play essential roles in sugar transport, but whether they have roles in senescence and the corresponding mechanism are unclear. Here, we functionally characterized a sugar transporter, OsSWEET1b, which transports sugar and promotes senescence in rice (Oryza sativa L.). OsSWEET1b could import glucose and galactose when heterologously expressed in Xenopus oocytes and translocate glucose and galactose from the extracellular apoplast into the intracellular cytosol in rice. Loss of function of OsSWEET1b decreased glucose and galactose accumulation in leaves. ossweet1b mutants showed accelerated leaf senescence under natural and dark-induced conditions. Exogenous application of glucose and galactose complemented the defect of OsSWEET1b deletion-promoted senescence. Moreover, the senescence-activated transcription factor OsWRKY53, acting as a transcriptional repressor, genetically functions upstream of OsSWEET1b to suppress its expression. OsWRKY53-overexpressing plants had attenuated sugar accumulation, exhibiting a similar phenotype as the ossweet1b mutants. Our findings demonstrate that OsWRKY53 downregulates OsSWEET1b to impair its influx transport activity, leading to compromised sugar accumulation in the cytosol of rice leaves where sugar starvation promotes leaf senescence.
Bayesian calibration of quasi-static field distortions in HARMONI
Authors: Carracedo Carballal Gonzalo J , Piqueras López Javier , Pereira Santaella Miguel , Clarke Fraser
Published: March 2024

The high angular resolution monolithic optical and near-infrared Integral field spectrograph is the first light visible and near-infrared integral field spectrograph for the Extremely Large Telescope. To reach the diffraction limit of the telescope (≈ 10 mas) and maintain an optimal image quality over long exposures, an accurate measurement of geometrical distortions in the instrument’s guide star field is needed. Geometrical distortions affecting the guide stars map directly to pointing errors of the science field. The systematic contribution to the pointing error can be calibrated and removed by a corrective model. In this work, we propose a formulation of the corrective model that aims to calibrate the geometrical field distortions down to a given target residual, as well as reducing the time spent in calibrations. We also propose a calibration procedure that accounts for the uncertainties of the measurement process. We developed a tool named harmoni-pm to simulate the expected pointing error caused by geometrical distortions and validate the effectiveness of the proposed corrective model. We also relied on pseudo Zernike polynomials to formulate the model, and the Bayesian theoretical framework to study the propagation of uncertainties along the calibration process. Compared with the classical calibration algorithm, the Bayesian calibration algorithm was able to reduce the number of calibration points required to reach the same model residual. Additionally, we were able to optimize the hardware of the Geometrical Calibration Unit and reduce the time required to achieve the calibration goal.
S-Adenosyl-l-Methionine Alleviates the Senescence of MSCs Through the PI3K/AKT/FOXO3a Signaling Pathway
Authors: Shang Lipeng , Li Xiaoxia , Ding Xiaoyan , Liu Guoxiang , Pan Zhen , Chen Xiangyan , Wang Yuelei , Li Bing , Wang Ting , Zhao Robert Chunhua
Published: March 2024

Cellular senescence significantly affects the proliferative and differentiation capacities of mesenchymal stem cells (MSCs). Identifying key regulators of senescence and exploring potential intervention strategies, including drug-based approaches, are active areas of research. In this context, S-adenosyl-l-methionine (SAM), a critical intermediate in sulfur amino acid metabolism, emerges as a promising candidate for mitigating MSC senescence. In a hydrogen peroxide-induced MSC aging model (100 μM for 2 hours), SAM (50 and 100 μM) was revealed to alleviate the senescence of MSCs, and also attenuated the level of reactive oxygen species and enhanced the adipogenic and osteogenic differentiation in senescent MSCs. In a premature aging mouse model (subcutaneously injected with 150 mg/kg/day d-galactose in the neck and back for 7 weeks), SAM (30 mg/kg/day by gavage for 5 weeks) was shown to delay the overall aging process while increasing the number and thickness of bone trabeculae in the distal femur. Mechanistically, activation of PI3K/AKT signaling and increased phosphorylation of forkhead box O3 (FOXO3a) was proved to be associated with the antisenescence role of SAM. These findings highlight that the PI3K/AKT/FOXO3a axis in MSCs could play a crucial role in MSCs senescence and suggest that SAM may be a potential therapeutic drug for MSCs senescence and related diseases.
A novel technique for the removal of retained Kirschner wires utilizing a cannulated drill bit
Authors: Nadeau Elizabeth K. , Rivas Gabriella A. , Oliver Christine , Reid Kristoff
Published: March 2024

A 35 year-old male with past history of severe open femur and tibia injury presented years after fracture fixation with a symptomatic retained Kirschner wire in his proximal tibia. A cannulated drill bit was used for removal after unsuccessful attempts using hand-held instruments. This case presents a technique for removal of a k-wire retained in bone for several years. This technique can be replicated in similar settings with cannulated drill bits from other commonly used orthopaedic device companies. Intraoperative removal of k-wires can be problematic, however, this technique offers a solution that balances implant removal and limiting destruction of surrounding tissue.
Native Australian Bronze Orange Stink Bug (Musgraveia sulciventris)–Related Corneal Injury
Authors: Seshakumaran Aishwariya
Published: March 2024

The bronze orange stink bug (Musgraveia sulciventris) is an insect native to Australia that is found in citrus trees and gardens in coastal Queensland and New South Wales. The common name “stink bug” is attributed to the foul spray emitted from these insects when they are threatened. This spray can result in corneal injuries; however, human case reports of stink bug bodily fluid exposure to the eye are rare and have not been previously reported for this species. This report describes a case of the native Australian insect bronze orange stink bug causing irritant contact keratitis in the eye, which is the only reported case in the literature. Patients who garden in Queensland and New South Wales should be advised to handle these insects with care, by wearing protective eyewear and gloves when handling citrus trees or when removing them from their gardens, to minimize their risk of corneal damage if sprayed.
Partial Identification of the Effects of Sustained Treatment Strategies
Authors: Diemer Elizabeth W. , Shi Joy , Swanson Sonja A.
Published: March 2024

Although many epidemiologic studies focus on point identification, it is also possible to partially identify causal effects under consistency and the data alone. However, the literature on the so-called “assumption-free” bounds has focused on settings with time-fixed exposures. We describe assumption-free bounds for the effects of both static and dynamic sustained interventions. To provide intuition for the width of the bounds, we also discuss a mathematical connection between assumption-free bounds and clone-censor-weight approaches to causal effect estimation. The bounds, which are often wide in practice, can provide important information about the degree to which causal analyses depend on unverifiable assumptions made by investigators.
A Novel Prolene Suture Pull-out Technique Combined with Anchor Technique for the Treatment of Tendinous Mallet Finger
Authors: Wang Fengxiong , Xiao Song , He Xiaowei , Zheng Dayin , Wu Man , Wang Xiaoting , Cai Liyun
Published: March 2024

Background:

Mallet finger deformity is a prevalent disability that causes discomfort and inconvenience to the patients. Despite the existence of various surgical approaches, surgical management remains a controversial subject.

Methods:

We retrospectively analyzed the clinical data of 26 patients with isolated tendinous mallet fingers who were admitted between January 2021 and June 2022. Among them, there were 18 men and eight women, aged between 20 and 56 years, with an average age of 38 years. The causes of injury were cutting injuries (15 cases), sports impact injuries (nine cases), and sprains (two cases). The time interval between injury and surgery ranged from 2 hours to 48 days, with an average of 12 days. During the surgical procedure, the distal interphalangeal joint was fixed in a mild dorsiflexion position using Kirschner wire. Absorbable anchors were used to assist in the reconstruction of the insertion point of the finger extensor tendon. Additionally, a 4-0 Prolene suture was used for reinforcement.

Results:

All 26 patients were followed up for a period ranging from 6 to 24 months, with an average follow-up duration of 9 months. The function of distal interphalangeal joint was preserved. According to the Crawford functional evaluation criteria, the function of the affected fingers was excellent in 15 cases, good in eight cases, fair in three cases, and poor in no cases.

Conclusions:

A novel Prolene suture pull-out technique is an effective approach to repair tendon mallet finger and reconstruct the tendon-bone anatomical unit. This treatment option provides favorable outcomes, with high rates of excellent and good functional results.
Superior Ophthalmic Vein Thrombosis Associated With Asymptomatic COVID-19 Infection
Authors: Menke Bryant A. , Ryu Christine , Chundury Rao V.
Published: March 2024

Superior ophthalmic vein thrombosis is a rare condition scarcely described in clinical literature with potentially severe consequences including permanent vision loss. This report details the case of a 70-year-old woman who presented with acute binocular horizontal diplopia, relative proptosis of the OD by 4 mm, and pain OD. On exam, visual acuity was 20/20 OD and 20/30 OS with full extraocular movements. CT revealed proptosis OD with a thrombosed superior ophthalmic varix. Evaluation for etiology of hypercoagulability was unremarkable, although the patient did have an asymptomatic COVID-19 infection 1 month prior. To the authors’ knowledge, this is the first reported case of superior ophthalmic vein thrombosis secondary to an asymptomatic COVID-19 infection.
Topical Application of Perchlorate: A Toxicity Study in Rats
Authors: Ulloa-Padilla Jan P. , Burkat Cat N. , Morgenstern Kenneth E.
Published: March 2024

Purpose:

To investigate the ocular safety profile of topical perchlorate as a potential preventive treatment for nasolacrimal obstruction associated with excessive use of radioactive iodine therapy.

Methods:

Nine Wistar male rats (18 eyes) were randomly assigned to receive an ocular application (topical eye drop on the OD, 3 times a day for 5 days) consisting of either: 1) sterile saline solution, 2) 30 mg/ml NaClO4 or 3) 30 mg/ml KClO4. The rat eyes were examined daily for corneal cloudiness/clarity, discharge, mucous secretions, conjunctival injection, eyelid erythema, and/or changes in behavior. Seven days after the first dose, the rats were euthanized and OU were harvested, fixed, embedded in paraffin, and stained with H&E and Masson’s trichrome using standard techniques.

Results:

The data collected over the 7 days revealed no behavior changes or ocular complications in any of the 3 study groups. Pathologic analysis of the corneas revealed normal findings on all groups without signs of inflammation, fibrosis, or any other abnormality, and no difference between the treated and control eyes.

Conclusions:

The findings of this study suggest that the use of topical perchlorate is safe to use on eyes in high concentrations. The efficacy of this compound in minimizing fibrosis of the nasolacrimal sac and duct warrants further study.
Determining the Degree of Perceptible Static Eyelid Asymmetry and Effect of Face Inversion: A Cross-sectional Pilot Study
Authors: Preston Frank G. , Sultan Ziyaad , Hsuan James , Hamill Kevin J. , McCormick Austin G.
Published: March 2024

Purpose:

To determine the degree of static eyelid asymmetry required to be perceptible and whether this is affected by image inversion.

Methods:

Images of 3 volunteers were digitally manipulated to have eyelid asymmetry of 0.5 mm, 1 mm, or 1.5 mm of 3 different types, upper lid ptosis, upper lid retraction, and lower lid retraction. Forty-nine laypersons stated whether the images were symmetrical or asymmetrical. A separate inversion survey, completed by 29 clinicians, consisted of symmetrical images and 1 mm asymmetrical images, with half being inverted.

Results:

Upper lid ptosis, upper lid retraction, and lower lid retraction were not detected by most laypeople at 0.5 mm of severity (18.9%, 6.7%, 18.9% detection, respectively) but all 3 were detected by the majority of participants once asymmetry reached 1 mm severity (65.7%, 61.8%, 51.0% detection, respectively) and rose to over 70% identification at 1.5 mm (92.2%, 73.5%, 73.5% detection, respectively). Inversion of the images led to 19.7% lower rates of correct identification of asymmetrical faces compared with images presented in the correct orientation (80.7% asymmetry identified in normal images, 61.0% inverted, p < 0.001).

Conclusions:

All asymmetries were detectable by a majority of laypersons at a severity of 1 mm. Image inversion decreases a clinician’s ability to detect a 1 mm asymmetry, indicating an impaired asymmetry perception in the intraoperative view. This study provides research to counsel patients with varying degrees of eyelid asymmetry.
Knowledge mapping and research trends on perioperative neurocognitive disorder from 1990 to 2022: A bibliometric analysis
Authors: Wen Pengfei , Luo Pan , Yang Mingyi , Huang Jingyuan , Long Yunfei , Liu Lin , Xu Peng
Published: March 2024

Introduction:

Perioperative neurocognitive disorder (PND) has attracted consistently increasing attention worldwide. However, there are few bibliometric studies that systematically evaluate this field. This study aimed to visualize the knowledge structure and research trends in PND through bibliometrics to help understand the future development of basic and clinical research.

Methods:

Literature related to PND in Web of Science and PubMed from 1990 to 2022 were collected through keywords retrospectively. Additionally, the source information, citation information, etc. of these publications were extracted. Finally, bibliometric analysis was performed by visualization software and statistical software.

Results:

There were 2837 articles and reviews in total. An exponential rise in PND-related publications was observed. China had the most publication, followed by the US and Germany. The institution with the most output and citations was Harvard University (149 papers, 8966 citations). The most prominent author was Marcantonio Edward R with 66 publications and 5721 citations. The journal with the highest productivity for PND research was Frontiers in Aging Neuroscience followed by Anesthesia and Analgesia. Keywords were identified as six topics, including POD, POCD, cardiac surgery, anesthesia, orthopedic surgery, and dementia. According to keyword analysis, the most recent popular keywords in PND research were prevention, older patients, emergence delirium, orthopedic surgery, and dexmedetomidine.

Conclusions:

Publications on PND are increasing at an alarming rate from 1990 to 2022. Current research and future trends will concentrate on the prevention and treatment of PND, as well as PND associated with orthopedic surgery in older adults.
Revolutionizing neurotherapeutics: blood-brain barrier-on-a-chip technologies for precise drug delivery
Authors: Kantawala Burhan , Shariff Sanobar , Ramadan Nagham , Fawaz Violette , Hassan Youmna , Mugisha Nadine , Yenkoyan Konstantin , Nazir Abubakar , Uwishema Olivier
Published: March 2024

Introduction:

The blood-brain barrier (BBB) is a critical neurovascular unit regulating substances' passage from the bloodstream to the brain. Its selective permeability poses significant challenges in drug delivery for neurological disorders. Conventional methods often fail due to the BBB's complex structure.

Aim:

The study aims to shed light on their pivotal role in revolutionizing neurotherapeutics and explores the transformative potential of BBB-on-a-Chip technologies in drug delivery research to comprehensively review BBB-on-a-chip technologies, focusing on their design, and substantiate advantages over traditional models.

Methods:

A detailed analysis of existing literature and experimental data pertaining to BBB-on-a-Chip technologies was conducted. Various models, their physiological relevance, and innovative design considerations were examined through databases like Scopus, EbscoHost, PubMed Central, and Medline. Case studies demonstrating enhanced drug transport through BBB-on-a-Chip models were also reviewed, highlighting their potential impact on neurological disorders.

Results:

BBB-on-a-Chip models offer a revolutionary approach, accurately replicating BBB properties. These microphysiological systems enable high-throughput screening, real-time monitoring of drug transport, and precise localization of drugs. Case studies demonstrate their efficacy in enhancing drug penetration, offering potential therapies for diseases like Parkinson's and Alzheimer's.

Conclusion:

BBB-on-a-Chip models represent a transformative milestone in drug delivery research. Their ability to replicate BBB complexities, offer real-time monitoring, and enhance drug transport holds immense promise for neurological disorders. Continuous research and development are imperative to unlock BBB-on-a-Chip models' full potential, ushering in a new era of targeted, efficient, and safer drug therapies for challenging neurological conditions.
Challenges and lessons learnt in the management of an HIV-exposed neonate with gastroschisis in a resource limited setting. case report
Authors: Turyasiima Munanura , Ahmed Fadumo Mohamed , Egesa Walufu Ivan , Twesigemukama Sabinah , Kyoshabire Joan
Published: March 2024

Introduction and importance:

The incidence of congenital abdominal wall defects is increasing, but few cases have been reported in the African population.

Case presentation:

We report a case of gastroschisis in a term neonate who was delivered through spontaneous vaginal delivery (SVD) in a remote health facility before transfer to a tertiary hospital in Uganda. Although there was no environmental exposure to teratogens, the major risk factor of Gastroschisis, the neonate was low birth weight, HIV-exposed, and the mother had not received folic acid supplementation during the first trimester, known risk factors of Gastroschisis. Physical examination revealed intrauterine growth restriction in addition to the findings of the abdominal wall defect.

Clinical discussion:

There were many missed opportunities in the management of this case which was marred by delayed essential care of the newborn, delayed surgical repair, and transfer to the tertiary surgical center. At the tertiary surgical center, a modified silo technique with delayed secondary closure was used to repair the defect, but the neonate still met its death before completing day 7 of life.

Conclusion:

This case of gastroschisis shows how the diagnosis and management of neonates born with major congenital structural abnormalities in resource-limited settings is still desirable due to lack of sophisticated medical care services to assist in early detection during pregnancy and early surgical intervention at birth to prevent associated mortality. We discuss the lessons learnt and provide recommendations for improvement in the care of neonates born with Abdominal Wall defects and other congenital birth defects.
Novel FOXL2 Mutation in an Ovarian Adult Granulosa Cell Tumor: Report of a Case With Diagnostic and Clinicopathologic Implications
Authors: Nagy Agnes , Niu Na , Ratner Elena , Hui Pei , Buza Natalia
Published: March 2024

Adult granulosa cell tumor, the most common malignant ovarian sex cord–stromal tumor, harbors the characteristic mutation c.402C>G (p.C134W) in the FOXL2 gene in ~90% to 95% of cases. To date, no other variants of FOXL2 mutations have been identified in these tumors. Here we report the first case of an adult granulosa cell tumor with a novel FOXL2 point mutation c.398C>T (p.A133V) presenting in a 64-year-old postmenopausal woman. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy for atypical endometrial hyperplasia and gross examination revealed an incidental 3.2 cm right ovarian mass with a solid, bright yellow, homogeneous cut surface. Microscopically, ~30% of the tumor showed a nested growth pattern composed of uniform tumor cells with oval nuclei and a moderate amount of pale cytoplasm, while the remaining areas consisted of a bland storiform fibromatous stroma. Reticulin stain demonstrated loss of the individual pericellular network within the nested areas, while the pericellular staining pattern was retained in the background stromal component. FOXL2 sequencing analysis was performed in both components and revealed a c.398C>T (p.A133V) mutation in the nested component, whereas wild-type FOXL2 sequence was identified in the fibromatous stroma. Sections from the uterus showed a low-grade endometrioid endometrial adenocarcinoma with superficial myometrial invasion. The patient underwent adjuvant vaginal cuff brachytherapy for the endometrial carcinoma and is alive and well at 8 months follow-up. This case illustrates that new FOXL2 mutations may be detected in ovarian sex cord–stromal tumors with increasing use of routine molecular testing, adding to the complexity of the pathologic diagnosis. In the right morphologic and clinical context, a FOXL2 mutation—even if it is different from the dominant hotspot mutation c.402C>G (p.C134W)—can support the diagnosis of adult granulosa cell tumor.
Allostatic Load in Childhood, Adolescence, and Young Adulthood: Are Assumptions of Measurement Invariance Warranted?
Authors: Holochwost Steven J. , Volpe Vanessa V. , Collins Abbey N. , Propper Cathi B. , Mills-Koonce W. Roger , Brown Eleanor D. , Jaffee Sara R.
Published: March 2024

Overview

Allostatic load represents the cumulative toll of chronic mobilization of the body’s stress response systems, as indexed by biomarkers. Higher levels of stress and disadvantage predict higher levels of allostatic load, which, in turn, predict poorer physical and mental health outcomes. To maximize the efficacy of prevention efforts, screening for stress- and disadvantage-associated health conditions must occur before middle age—that is, during childhood, adolescence, and young adulthood. However, this requires that models of allostatic load display properties of measurement invariance across age groups. Because most research on allostatic load has featured older adults, it is unclear if these requirements can be met.

Methods

To address this question, we fit a series of exploratory and confirmatory analytic models to data on eight biomarkers using a nationally representative sample of N = 4260 children, adolescents, and young adults drawn from the National Health and Nutrition Examination Survey dataset.

Results

Exploratory and confirmatory models indicated that, consistent with allostatic load theory, a unidimensional model was a good fit to the data. However, this model did not display properties of measurement invariance; post-hoc analyses suggested that the biomarkers included in the final confirmatory model were most strongly intercorrelated among young adults and most weakly intercorrelated among adolescents.

Conclusions

These results underscore the importance of testing assumptions about measurement invariance in allostatic load before drawing substantive conclusions about stress, disadvantage, and health by directly comparing levels of allostatic load across different stages of development, while underscoring the need to expand investigations of measurement invariance to samples of longitudinal data.
Objective and Subjective Intraindividual Variability in Sleep: Predisposing Factors and Health Consequences
Authors: Gao Chenlu , Scullin Michael K.
Published: March 2024

Objective

We investigated the factors that predispose or precipitate greater intraindividual variability (IIV) in sleep. We further examined the potential consequences of IIV on overall sleep quality and health outcomes, including whether these relationships were found in both self-reported and actigraphy-measured sleep IIV.

Methods

In Study 1, 699 US adults completed a Sleep Intra-Individual Variability Questionnaire and self-reported psychosocial, sleep quality, and health outcomes. In Study 2, 100 university students wore actigraphy and completed psychosocial, sleep, and health surveys at multiple timepoints.

Results

In cross-sectional analyses that controlled for mean sleep duration, predisposing/precipitating factors to greater IIV were being an underrepresented racial/ethnic minority (Study 1: F = 13.95, p < .001; Study 2: F = 7.03, p = .009), having greater stress (Study 2: r values ≥ 0.32, p values ≤ .002) or trait vulnerability to stress (Study 1: r values ≥ 0.15, p values < .001), and showing poorer time management (Study 1: r values ≤ −0.12, p values ≤ .004; Study 2: r values ≤ −0.23, p values ≤ .028). In addition, both studies showed that greater sleep IIV was associated with decreased overall sleep quality, independent of mean sleep duration (Study 1: r values ≥ 0.20, p values < .001; Study 2: r values ≥ 0.33, p values ≤ .001). Concordance across subjective and objective IIV measures was modest (r values = 0.09–0.35) and similar to concordance observed for subjective-objective mean sleep duration measures.

Conclusion

Risk for irregular sleep patterns is increased in specific demographic groups and may be precipitated by, or contribute to, higher stress and time management inefficiencies. Irregular sleep may lead to poor sleep quality and adverse health outcomes, independent of mean sleep duration, underscoring the importance of addressing sleep consistency.
Establishing Nursing-Sensitive Quality Indicators for the Central Sterile Supply Department: A Modified Delphi Study
Authors: Hu Ruixue , Chen Yanhua , Hu Juan , Yi Liangying
Published: March 2024

Background and Objectives:

Previous studies have shown that improving quality management in the central sterile supply department (CSSD) is an effective measure to control and decrease hospital-acquired infections. This study aimed to establish nursing-sensitive quality indicators for CSSD nursing in China.

Methods:

We drafted nursing-sensitive quality indicators on the basis of the Structure-Process-Outcome model, and then conducted 2 rounds of consultation with experts using a modified Delphi method to determine the indicators and scientific methods of measurement.

Results:

We identified five CSSD nursing-sensitive quality indicators. Recovery rates of the 2 rounds of valid questionnaires were 100%. Expert authority coefficients were 0.810 and 0.902, respectively. Kendall's coefficients of concordance were 0.168 and 0.210, respectively (P < .05).

Conclusion:

Evidence-based nursing-sensitive quality indicators for the CSSD were established.
How do stochastic processes and genetic threshold effects explain incomplete penetrance and inform causal disease mechanisms?
Authors: Jenkins Dagan
Published: March 2024

Incomplete penetrance is the rule rather than the exception in Mendelian disease. In syndromic monogenic disorders, phenotypic variability can be viewed as the combination of incomplete penetrance for each of multiple independent clinical features. Within genetically identical individuals, such as isogenic model organisms, stochastic variation at molecular and cellular levels is the primary cause of incomplete penetrance according to a genetic threshold model. By defining specific probability distributions of causal biological readouts and genetic liability values, stochasticity and incomplete penetrance provide information about threshold values in biological systems. Ascertainment of threshold values has been achieved by simultaneous scoring of relatively simple phenotypes and quantitation of molecular readouts at the level of single cells. However, this is much more challenging for complex morphological phenotypes using experimental and reductionist approaches alone, where cause and effect are separated temporally and across multiple biological modes and scales. Here I consider how causal inference, which integrates observational data with high confidence causal models, might be used to quantify the relative contribution of different sources of stochastic variation to phenotypic diversity. Collectively, these approaches could inform disease mechanisms, improve predictions of clinical outcomes and prioritize gene therapy targets across modes and scales of gene function.

This article is part of a discussion meeting issue ‘Causes and consequences of stochastic processes in development and disease’.
Transcriptional priming and chromatin regulation during stochastic cell fate specification
Authors: Ordway Alison J. , Helt Rina N. , Johnston Robert J.
Published: March 2024

Stochastic cell fate specification, in which a cell chooses between two or more fates with a set probability, diversifies cell subtypes in development. Although this is a vital process across species, a common mechanism for these cell fate decisions remains elusive. This review examines two well-characterized stochastic cell fate decisions to identify commonalities between their developmental programmes. In the fly eye, two subtypes of R7 photoreceptors are specified by the stochastic ON/OFF expression of a transcription factor,
spineless
. In the mouse olfactory system, olfactory sensory neurons (OSNs) randomly select to express one copy of an olfactory receptor (OR) gene out of a pool of 2800 alleles. Despite the differences in these sensory systems, both stochastic fate choices rely on the dynamic interplay between transcriptional priming, chromatin regulation and terminal gene expression. The coupling of transcription and chromatin modifications primes gene loci in undifferentiated neurons, enabling later expression during terminal differentiation. Here, we compare these mechanisms, examine broader implications for gene regulation during development and posit key challenges moving forward.

This article is part of a discussion meeting issue ‘Causes and consequences of stochastic processes in development and disease’.