bluuebunny/crossref_metadata_2025 huggingface dataset:
Foreign Policy as Compensation: Why Brexit Became a Foreign and Security Policy Issue
Authors: Martill Benjamin , Mesarovich Alexander
Published: March 2024

Exogenous reform demands can put leaders in a tight spot where change runs up against structural impediments. Yet, where asymmetries in reform costs occur across domains, leaders can seek to re-frame the impetus of change from one domain to another. Such compensatory behavior is commonplace but is not adequately captured by existing research on linkage politics, forum shopping, or diversionary conflict. This article develops the concept of compensatory foreign policy, whereby leaders use foreign policy change to compensate for unviable economic reforms when they have greater capacity and choice in the former domain. Empirically, we use elite interviews to reconstruct the politics of security policy in the post-Brexit United Kingdom, showing how party leaders focused on foreign policy change when beneficial economic arrangements were precluded. Our argument contributes to recent research on linkage politics by demonstrating the conditions under which leaders seek foreign policy reforms to compensate for economic weakness.
Centralized Interactive Phenomics Resource: an integrated online phenomics knowledgebase for health data users
Authors: Honerlaw Jacqueline , Ho Yuk-Lam , Fontin Francesca , Murray Michael , Galloway Ashley , Heise David , Connatser Keith , Davies Laura , Gosian Jeffrey , Maripuri Monika , Russo John , Sangar Rahul , Tanukonda Vidisha , Zielinski Edward , Dubreuil Maureen , Zimolzak Andrew J , Panickan Vidul A , Cheng Su-Chun , Whitbourne Stacey B , Gagnon David R , Cai Tianxi , Liao Katherine P , Ramoni Rachel B , Gaziano J Michael , Muralidhar Sumitra , Cho Kelly
Published: March 2024

Objective

Development of clinical phenotypes from electronic health records (EHRs) can be resource intensive. Several phenotype libraries have been created to facilitate reuse of definitions. However, these platforms vary in target audience and utility. We describe the development of the Centralized Interactive Phenomics Resource (CIPHER) knowledgebase, a comprehensive public-facing phenotype library, which aims to facilitate clinical and health services research.

Materials and Methods

The platform was designed to collect and catalog EHR-based computable phenotype algorithms from any healthcare system, scale metadata management, facilitate phenotype discovery, and allow for integration of tools and user workflows. Phenomics experts were engaged in the development and testing of the site.

Results

The knowledgebase stores phenotype metadata using the CIPHER standard, and definitions are accessible through complex searching. Phenotypes are contributed to the knowledgebase via webform, allowing metadata validation. Data visualization tools linking to the knowledgebase enhance user interaction with content and accelerate phenotype development.

Discussion

The CIPHER knowledgebase was developed in the largest healthcare system in the United States and piloted with external partners. The design of the CIPHER website supports a variety of front-end tools and features to facilitate phenotype development and reuse. Health data users are encouraged to contribute their algorithms to the knowledgebase for wider dissemination to the research community, and to use the platform as a springboard for phenotyping.

Conclusion

CIPHER is a public resource for all health data users available at https://phenomics.va.ornl.gov/ which facilitates phenotype reuse, development, and dissemination of phenotyping knowledge.
B-1a cells scavenge NETs to attenuate sepsis
Authors: Murata Kensuke , Murao Atsushi , Tan Chuyi , Wang Ping , Aziz Monowar
Published: March 2024

B-1a cells, a regulatory subset of B lymphocytes, produce natural IgM and interleukin-10. Neutrophil extracellular traps (NETs) play a crucial role in pathogen defense, but their excessive formation during sepsis can cause further inflammation and tissue damage. In sepsis, extracellular cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern, is released to induce NET formation. We hypothesize that B-1a cells clear NETs to prevent sepsis-induced injury. Sepsis in mice was induced by injecting 1 × 107 and 5 × 107 colony-forming units of Escherichia coli intraperitoneally. After 4 and 20 h, we assessed the number of B-1a cells in the peritoneal cavity using flow cytometry. Our results showed that the number of peritoneal B-1a cells was significantly decreased in E. coli sepsis mice. Importantly, replenishing B-1a cells via intraperitoneal injection in sepsis mice significantly decreased NETs in peritoneal neutrophils. We also observed a decrease in serum inflammation and injury markers and a significant increase in the overall survival rate in B-1a cell–treated septic mice. To understand the mechanism, we cocultured bone marrow–derived neutrophils with peritoneal B-1a cells in a contact or noncontact condition using an insert and stimulated them with eCIRP. After 4 h, we found that eCIRP significantly increased NET formation in bone marrow–derived neutrophils. Interestingly, we observed that B-1a cells inhibited NETs by 67% in a contact-dependent manner. Surprisingly, when B-1a cells were cultured in inserts, there was no significant decrease in NET formation, suggesting that direct cell-to-cell contact is crucial for this inhibitory effect. We further determined that B-1a cells promoted NET phagocytosis, and this was mediated through natural IgM, as blocking the IgM receptor attenuated the engulfment of NETs by B-1a cells. Finally, we identified that following their engulfment, NETs were localized into the lysosomal compartment for lysis. Thus, our study suggests that B-1a cells decrease NET content in eCIRP-treated neutrophils and E. coli sepsis mice.
Evolutionary correspondence analysis of the semantic dynamics of frames
Authors: Baden Christian , Motta Giovanni
Published: March 2024

We introduce and implement a novel dimension-reduction method for high-dimensional time-varying contingency-tables: the Evolutionary Correspondence Analysis (ECA). ECA enables a comparative analysis of high-dimensional, diachronic processes by identifying a small number of shared latent variables that shape co-evolving data patterns. ECA offers new opportunities for the study of complex social phenomena, such as co-evolving public debates: Its capacity to inductively extract time-varying latent variables from observed contents of evolving debates permits an analysis of meanings shared by linked sub-discourses, such as linked national public spheres or the discourses led by distinct political camps within a shared public sphere. We illustrate the utility of our approach by studying how the Greek and German right-, centre-, and left-leaning news coverage of the European financial crisis evolved between its outbreak in 2009 until its institutional containment in 2012. Comparing the use of 525 unique concepts in six German and Greek outlets with different political leaning over an extended period of time, we identify two common factors accounting for those evolving meanings and analyse how the different sub-discourses influenced one another over time. We allow the factor loadings to be time-varying, and fit to the latent factors a time-varying vector-auto-regressive model with time-varying mean.
GENIUS-MAWII: for robust Mendelian randomization with many weak invalid instruments
Authors: Ye Ting , Liu Zhonghua , Sun Baoluo , Tchetgen Tchetgen Eric
Published: March 2024

Mendelian randomization (MR) addresses causal questions using genetic variants as instrumental variables. We propose a new MR method, G-Estimation under No Interaction with Unmeasured Selection (GENIUS)-MAny Weak Invalid IV, which simultaneously addresses the 2 salient challenges in MR: many weak instruments and widespread horizontal pleiotropy. Similar to MR-GENIUS, we use heteroscedasticity of the exposure to identify the treatment effect. We derive influence functions of the treatment effect, and then we construct a continuous updating estimator and establish its asymptotic properties under a many weak invalid instruments asymptotic regime by developing novel semiparametric theory. We also provide a measure of weak identification, an overidentification test, and a graphical diagnostic tool.
Plant metabolomics
Authors: Li-Beisson Yonghua , Hirai Masami Yokota , Nakamura Yuki
Published: March 2024

Plants are a treasure trove of metabolic compounds. The chemical diversity of plant cells has developed and been maintained through evolution and metabolic regulation, and plays a crucial role in plant physiology, development, and adaption to changing environmental situations. Metabolomics, when combined with genomics and proteomics, has opened up unprecedented opportunities to address the biological importance of metabolic diversity. It has also provided an avenue for metabolic engineering to produce a particular compound of interest to meet societal and economical demands, an important effort to achieve sustainable development. This Special Issue therefore focuses on current trends in plant metabolomics research, providing examples in the development of analytical technologies, the functional study of plant metabolism, and applications to synthetic and engineering biology.
Alternative pathways leading to ascorbate biosynthesis in plants: lessons from the last 25 years
Authors: Quiñones Cherryl O , Gesto-Borroto Reinier , Wilson Rachael V , Hernández-Madrigal Sara V , Lorence Argelia
Published: March 2024

l-Ascorbic acid (AsA) is an antioxidant with important roles in plant stress physiology, growth, and development. AsA also plays an essential role in human health, preventing scurvy. Humans do not synthesize AsA, which needs to be supplied via a diet rich in fresh produce. Research efforts have provided progress in the elucidation of a complex metabolic network with at least four routes leading to AsA formation in plants. In this review, three alternative pathways, namely the d-galacturonate, the l-gulose, and the myo-inositol pathways, are presented with the supporting evidence of their operation in multiple plant species. We critically discuss feeding studies using precursors and their conversion to AsA in plant organs, and research where the expression of key genes encoding enzymes involved in the alternative pathways showed >100% AsA content increase in the transgenics and in many cases accompanied by enhanced tolerance to multiple stresses. We propose that the alternative pathways are vital in AsA production in response to stressful conditions and to compensate in cases where the flux through the d-mannose/l-galactose pathway is reduced. The genes and enzymes that have been characterized so far in these alternative pathways represent important tools that are being used to develop more climate-tolerant crops.
Comparison of markers to estimate microbial adherence and fibrolytic activity in forages after in vitro incubation
Authors: Mezzomo Mariana P , Stefanello Simone , Castro Luis A S , Kozloski Gilberto V
Published: March 2024

The aims of this study were to evaluate the relationship between attached microbial markers and degradability of forage samples incubated in vitro and to compare these microbial markers. In Trial 1, the content of 15N, purines, and phosphorus (P) as well as xylanase activity in residue of different forage species were measured after 24 h of incubation in a conventional in vitro system at pH 6.8. Trial 2 used the same procedures as those of Trial 1 except that forage samples were incubated in media with different initial pH (5.5, 6.0, 6.5, or 7.0). There was no correlation (P > 0.10) between forage degradability and either microbial marker in Trial 1. Degradability of both, bermuda and ryegrass, and the content of all markers in the incubation residues was positively affected by increased pH (P < 0.05). The content of 15N in residues was linearly related to xylanase activity (P < 0.05) but not with P or purines content. In conclusion, the nutritional potential of different forage species may not to be compared, based on the content of microbial markers in the incubation residues. In other way, within a forage species, the in vitro degradation was directly associated to either marker. However, P presents analytical advantage over other markers.
Cosmic variance suppression in radiation-hydrodynamic modelling of the reionization-era 21-cm signal
Authors: Acharya Anshuman , Garaldi Enrico , Ciardi Benedetta , Ma Qing-bo
Published: March 2024

The 21-cm line emitted by neutral hydrogen is the most promising probe of the Epoch of Reionization (EoR). Multiple radio interferometric instruments are on the cusp of detecting its power spectrum. It is therefore essential to deliver robust theoretical predictions, enabling sound inference of the coeval Universe properties. The nature of this signal traditionally required the modelling of $\mathcal {O}(10^{7-8} \, {\rm Mpc}^3)$ volumes to suppress the impact of cosmic variance. However, the recently proposed Fixed & Paired (F&P) approach uses carefully crafted simulation pairs to achieve equal results in smaller volumes. In this work, we thoroughly test the applicability of and improvement granted by this technique to different observables of the 21-cm signal from the EoR. We employ radiation-magneto-hydrodynamics simulations to ensure the most realistic physical description of this epoch, greatly improving over previous studies using a seminumerical approach without accurate galaxy formation physics and radiative transfer. We estimate the statistical improvement granted by the F&P technique on predictions of the skewness, power spectrum, bispectrum, and ionized regions size distribution of the 21-cm signal at redshift 7 ≤ z ≤ 10 (corresponding to ${\ge}80{{\ \rm per\ cent}}$ of the gas being neutral). We find that the effective volume of F&P simulations is at least 3.5 times larger than traditional simulations. This directly translates into an equal improvement in the computational cost (in terms of time and memory). Finally, we confirm that a combination of different observables like skewness, power spectrum, and bispectrum across different redshifts can be utilized to maximize the improvement.
Deciphering recursive polyploidization in Lamiales and reconstructing their chromosome evolutionary trajectories
Authors: Wang Jiangli , Song Bowen , Yang Minran , Hu Fubo , Qi Huilong , Zhang Huizhe , Jia Yuelong , Li Yingjie , Wang Zhenyi , Wang Xiyin
Published: March 2024

Lamiales is an order of core eudicots with abundant diversity, and many Lamiales plants have important medicinal and ornamental values. Here, we comparatively reanalyzed 11 Lamiales species with well-assembled genome sequences and found evidence that Lamiales plants, in addition to a hexaploidization or whole-genome triplication (WGT) shared by core eudicots, experienced further polyploidization events, establishing new groups in the order. Notably, we identified a whole-genome duplication (WGD) occurred just before the split of Scrophulariaceae from the other Lamiales families, such as Acanthaceae, Bignoniaceae, and Lamiaceae, suggesting its likely being the causal reason for the establishment and fast divergence of these families. We also found that a WGT occurred ∼68 to 78 million years ago (Mya), near the split of Oleaceae from the other Lamiales families, implying that it may have caused their fast divergence and the establishment of the Oleaceae family. Then, by exploring and distinguishing intra- and intergenomic chromosomal homology due to recursive polyploidization and speciation, respectively, we inferred that the Lamiales ancestral cell karyotype had 11 proto-chromosomes. We reconstructed the evolutionary trajectories from these proto-chromosomes to form the extant chromosomes in each Lamiales plant under study. We must note that most of the inferred 11 proto-chromosomes, duplicated during a WGD thereafter, have been well preserved in jacaranda (Jacaranda mimosifolia) genome, showing the credibility of the present inference implementing a telomere-centric chromosome repatterning model. These efforts are important to understand genome repatterning after recursive polyploidization, especially shedding light on the origin of new plant groups and angiosperm cell karyotype evolution.
DNA methylation clocks for estimating biological age in Chinese cohorts
Authors: Zheng Zikai , Li Jiaming , Liu Tianzi , Fan Yanling , Zhai Qiao-Cheng , Xiong Muzhao , Wang Qiao-Ran , Sun Xiaoyan , Zheng Qi-Wen , Che Shanshan , Jiang Beier , Zheng Quan , Wang Cui , Liu Lixiao , Ping Jiale , Wang Si , Gao Dan-Dan , Ye Jinlin , Yang Kuan , Zuo Yuesheng , Ma Shuai , Yang Yun-Gui , Qu Jing , Zhang Feng , Jia Peilin , Liu Guang-Hui , Zhang Weiqi
Published: March 2024

Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation (DNAm) at specific CpG sites. However, a systematic comparison between DNA methylation data and other omics datasets has not yet been performed. Moreover, available DNAm age predictors are based on datasets with limited ethnic representation. To address these knowledge gaps, we generated and analyzed DNA methylation datasets from two independent Chinese cohorts, revealing age-related DNAm changes. Additionally, a DNA methylation aging clock (iCAS-DNAmAge) and a group of DNAm-based multi-modal clocks for Chinese individuals were developed, with most of them demonstrating strong predictive capabilities for chronological age. The clocks were further employed to predict factors influencing aging rates. The DNAm aging clock, derived from multi-modal aging features (compositeAge-DNAmAge), exhibited a close association with multi-omics changes, lifestyles, and disease status, underscoring its robust potential for precise biological age assessment. Our findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace, providing the basis for evaluating aging intervention strategies.
Flare prediction after tapering the dose of tumour necrosis factor inhibitors in patients with axial spondyloarthritis: a nationwide cohort study
Authors: Yeo Jina , Kim Ju Yeon , Park Jin Kyun , Shin Kichul , Lee Eun Young , Kim Tae-Hwan , Park Jun Won
Published: March 2024

Objectives

To develop a model for predicting flares after tapering the dose of tumour necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA).

Methods

Data were obtained from the Korean College of Rheumatology Biologics and Targeted Therapy Registry. In total, 526 patients who received the standard-dose TNFi for at least 1 year and tapered their dose were included in the derivation cohort. The main outcome was a flare occurrence defined as an Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) score of ≥2.1 after 1 year of TNFi tapering. The final prediction model was validated using an independent cohort.

Results

Among 526 patients, 127 (24.1%) experienced flares. The final prediction model included negative human leucocyte antigen B27 (β = 1.088), inflammatory back pain (β = 1.072), psoriasis (β = 1.567), family history of SpA (β = 0.623), diabetes mellitus (β = 1.092), TNFi tapering by ≥50% of the standard-dose (β = 0.435), ASDAS-CRP at tapering (β = 1.029), and Bath Ankylosing Spondylitis Functional Index score at tapering (β = 0.194) as covariates. It showed an excellent discrimination performance (AUC = 0.828). According to the predictive risk, patients were classified into three groups (low-, intermediate- and high-risk). The probabilities of flares in these groups were 4.5%, 18.1% and 61.8%, respectively. The performance of the model in the validation cohort was also comparable.

Conclusion

The established prediction model accurately predicted the risk of flares after TNFi dose tapering in patients with axSpA using eight simple clinical parameters, which could be helpful to select appropriate patients for tapering their TNFi without flare in daily clinical practice.
Hydroxychloroquine in lupus or rheumatoid arthritis pregnancy and risk of major congenital malformations: a population-based cohort study
Authors: Nguyen Ngoc V , Svenungsson Elisabet , Dominicus Annica , Altman Maria , Hellgren Karin , Simard Julia F , Arkema Elizabeth V
Published: March 2024

Objectives

To assess the infant risk of major congenital malformations (MCM) associated with first-trimester exposure to hydroxychloroquine (HCQ) among mothers with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).

Methods

This population-based cohort study utilized Swedish nationwide registers and included all singleton births (2006–2021) among individuals with prevalent SLE or RA in Sweden. The exposure was filling ≥1 HCQ prescription during the first trimester. The outcome was infant MCM within 1 year of birth. Inverse probability of treatment weighting was applied to adjust for potential confounders (e.g. maternal smoking, body mass index, pregestational diabetes and corticosteroids). Modified Poisson regression models with robust variance were used to estimate risk ratios (RR) and 95% CI.

Results

We included 1007 births (453 exposed) and 2500 births (144 exposed) in the SLE and RA cohorts, respectively. The MCM risks in the SLE overall cohort, exposed and unexposed groups were 3.6%, 3.7% and 3.4%, respectively. The corresponding figures in the RA cohort were 4.4%, 5.6% and 4.3%, respectively. The adjusted RRs (95% CI) were 1.29 (0.65, 2.56) in the SLE cohort, 1.32 (0.56, 3.13) in the RA cohort and 1.30 (0.76, 2.23) in the pooled analysis. The adjusted risk difference (exposed vs unexposed) was small (0.9% in SLE and 1.3% in RA). Sensitivity analyses examining different exposure and outcome windows yielded similar findings.

Conclusion

First-trimester exposure to HCQ was not associated with a significantly increased risk of MCM. HCQ’s benefits may outweigh the risks in managing SLE or RA during pregnancy.
Can complement activation be the missing link in antiphospholipid syndrome?
Authors: Venturelli Veronica , Maranini Beatrice , Tohidi-Esfahani Ibrahim , Isenberg David A , Cohen Hannah , Efthymiou Maria
Published: March 2024

APS is an autoimmune disorder with life-threatening complications that, despite therapeutic advantages, remains associated with thrombotic recurrences and treatment failure. The role of complement activation in APS pathogenesis is increasingly recognized, specifically in obstetric APS. However, its exact role in thrombotic APS and on the severity of the disease is not yet fully elucidated. Further mechanistic studies are needed to delineate the role of complement activation in the various APS clinical manifestations with aim to identify novel markers of disease severity, together with clinical trials to evaluate the efficacy of complement inhibition in APS. This could ultimately improve risk stratification in APS, patient-tailored targeted therapy with complement inhibition identified as an adjunctive treatment. This article reviews current findings and challenges about complement activation in APS, discusses the potential role of platelet-mediated complement activation in this setting and provides an overview of clinical implications and current therapeutics.
The electric vehicle routing problem of a new mobile charging service
Authors: Ren Kanghui , Li Maosheng , Cen Xuekai , Huang Helai
Published: March 2024

A novel mobile charging service that utilizes vehicle-to-vehicle (V2V) charging technology has recently been proposed as a supplement to fixed charging infrastructure (CI), enabling electric vehicles (EVs) to exchange electricity. This study formulates a vehicle routing problem (VRP) of vehicle-to-vehicle (V2V) charging, optimizing the routing of DVs to service RVs while taking into account their willingness to join the V2V charging platform. A mixed integer linear programming (MILP) model is established to optimize the VRP-V2V (i.e. the VRP of V2V charging), which is known to be NP-hard. To solve large-scale instances for real-world applications, we propose an adaptive large neighborhood search (ALNS) algorithm, which, when combined with the structure of the VRP-V2V problem, utilizes four local search procedures to enhance solution quality following destroy and repair operators. Results indicate that the proposed ALNS algorithm outperforms the optimization solver CPLEX in small-scale instances, and can solve large-scale instances that are infeasible using CPLEX solver. In a numerical analysis of Changsha's large-scale network, we demonstrate that the V2V platform can save an average of 33.1% on the charging cost of recharging vehicles, hence raising customer satisfaction with charging services and reducing range anxiety. The platform's profitability is also increased by using V2V charging in areas lacking fixed charging infrastructure.
A Contemporary View of Menopausal Hormone Therapy
Authors: Levy Barbara , Simon James A.
Published: March 2024

Enthusiasm for the use of hormones to ameliorate symptoms of perimenopause and menopause has waxed and waned over the years. Both treatment for symptoms and training of women's health care practitioners in the management of menopause have sharply declined since publication of the Women's Health Initiative initial results in 2002. Findings from that trial, which treated a population of older, asymptomatic patients, have been extrapolated over the past 21 years to all estrogen products, all menopausal women, and all delivery mechanisms. Our patients deserve a more nuanced, individualized approach. Conjugated equine estrogens and medroxyprogesterone acetate are no longer the predominant medications or medications of choice available for management of menopausal symptoms. All hormones are not equivalent any more than all antiseizure medications or all antihypertensives are equivalent; they have different pharmacodynamics, duration of action, and affinity for receptors, among other things, all of which translate to different risks and benefits. Consideration of treatment with the right formulation, at the right dose and time, and for the right patient will allow us to recommend safe, effective, and appropriate treatment for people with menopausal symptoms.
Association Between Intrapartum Nitrous Oxide for Labor Analgesia and Short-Term Neonatal Outcomes
Authors: Starosta Anabel , Lundsberg Lisbet , Culhane Jennifer , Partridge Caitlin , Grechukhina Olga , Son Moeun
Published: March 2024

OBJECTIVE:

To evaluate the association between intrapartum nitrous oxide use and adverse short-term neonatal outcomes.

METHODS:

This was a retrospective cohort study of individuals with singleton gestations at 35 or more weeks who attempted labor and delivered at an academic hospital between June 1, 2015, and February 28, 2020. Data were extracted from the electronic medical record using billing and diagnostic codes. Patients were classified based on whether they received no intrapartum analgesia or received nitrous oxide only. Those who received other analgesia types were excluded. The primary outcome was neonatal intensive care unit (NICU) admission. Secondary outcomes included Apgar score less than 7 at 1 minute and 5 minutes, respiratory composite outcome (including meconium aspiration syndrome, neonatal bronchopulmonary disorders, neonatal transient tachypnea, and other neonatal respiratory distress that required NICU admission), hypoglycemia, and hyperbilirubinemia. Univariable and multivariable analyses were used to estimate the association between nitrous oxide exposure intrapartum and the selected outcomes.

RESULTS:

Of 6,047 included, 4,153 (68.7%) received no analgesia, and 1,894 (31.3%) received nitrous oxide only. In comparison with individuals who received no analgesia, those who received nitrous oxide were more likely to be nulliparous, be of Black racial identity, have noncommercial insurance, and be less likely to deliver by intrapartum cesarean. The reception of nitrous oxide, compared with the reception of no analgesia, was associated with a lower likelihood of NICU admission (6.4% vs 8.1%; adjusted odds ratio [aOR] 0.77, 95% CI, 0.62–0.96) and an increased likelihood of neonatal hyperbilirubinemia (aOR 1.23, 95% CI, 1.08–1.41). Inhaled nitrous oxide exposure, in comparison with the reception of no analgesia, was not associated with the other secondary outcomes, including Apgar score less than 7 at 1 minute (odds ratio [OR] 0.74, 95% CI, 0.50–1.10) or 5 minutes (OR 0.91, 95% CI, 0.32–2.60), respiratory composite outcome (OR 0.91, 95% CI, 0.70–1.17), and hypoglycemia (OR 0.82, 95% CI, 0.64–1.05).

CONCLUSION:

In this single-center retrospective cohort of low-risk patients, intrapartum inhaled nitrous oxide, compared with the reception of no analgesia, was associated with a decreased risk for NICU admission but with an increased risk for hyperbilirubinemia; other outcomes did not differ. These findings may be used to counsel patients when considering nitrous oxide for labor analgesia.
WALANT office based endoscopic cubital tunnel release
Authors: Hoelscher Victoria , Pientka William F.
Published: March 2024

Background:

Cubital tunnel syndrome is a common condition caused by compression of the ulnar nerve around the medial elbow. Surgical treatment usually involves open in situ ulnar nerve decompression unless ulnar nerve instability is noted. Endoscopic techniques for cubital tunnel release have been developed and implemented with excellent patient and surgeon satisfaction. Endoscopic cubital tunnel release can be performed in an office based procedure room under wide awake local anesthesia no tourniquet principles. We present our setup and technique for performing an endoscopic cubital tunnel release procedure in an office based setting under local anesthesia.

Methods:

Local anesthesia is injected along the course of the ulnar nerve on the medial arm and forearm extending 10 cm proximal and distal to the medial epicondyle. After allowing approximately 30 min for appropriate vasoconstriction, the patient is placed in a supine position with the arm abducted and externally rotated position. The endoscopic cubital tunnel release is then performed.

Discussion:

Our described technique eliminates the need for placement of a prophylactic tourniquet and thereby the need for the procedure to be performed within an OR setting. It also utilizes a single-stage anesthetic administration, which facilitates ease of completion and performance in an office based setting. There is a significant cost savings when endoscopic cubital tunnel release is performed in an office-based procedure room compared to in the operating room.

Conclusions:

Office-based endoscopic cubital tunnel release can be safely performed utilizing WALANT techniques, leading to high patient satisfaction and decreased overall cost of care.

Level of Evidence:

Therapeutic IV
Extracorporeal Photopheresis as a Treatment Option for Immune-Related Adverse Events: Two Case Reports and a Prospective Study
Authors: Ruf Theresa , Rahimi Farnaz , Anz David , Tufman Amanda , Salzer Suzanna , Zierold Sarah , Tomsitz Dirk , French Lars E. , Heinzerling Lucie
Published: March 2024

The wide use of immune checkpoint inhibitors has increased the frequency of immune-related adverse events (irAEs). While many are managed with corticosteroids or hormone substitution, up to 14.9% of irAEs are steroid-refractory or steroid-dependent and thus require second-line treatment. These should reduce irAE-related morbidity and mortality and induce a few side effects of their own while maintaining the antitumor response. There is little comparative data on second-line therapies for irAEs. Two cases of irAEs could not be sufficiently managed with corticosteroids and subsequently received treatment with extracorporeal photopheresis (ECP), including one patient with immune-related erosive oral lichen planus and one patient with immune-related colitis. In both cases, the irAE resolved with ECP in combination with immunosuppressive drugs, that is 4 weeks and 10 weeks after the start of ECP, respectively. To investigate this approach, a prospective clinical study that compares ECP and other second-line therapies for the treatment of steroid-refractory and steroid-dependent irAEs with regard to immunophenotype and therapy response has been designed. ECP could be a treatment option for steroid-refractory and steroid-dependent irAEs, given its good safety profile and lack of adverse effects on antitumor response. Comparative prospective studies are needed to generate an evidence base.
Great Toe Tip Reconstruction after Severe COVID-19 Using Hemi-pulp V-Y Advancement Flap: A Case Report
Authors: Hane Rika , Akita Shinsuke , Kubo Yohei , Takei Masahiro , Mitsukawa Nobuyuki
Published: March 2024

“COVID toe,” one of the extrapulmonary disorders of coronavirus disease 2019 (COVID-19), may result in toe necrosis. In this case, we successfully reconstructed a severe COVID-19-induced defect in the great toe by using an innervated hemi-pulp V-Y advancement flap. A 48-year-old woman was diagnosed with fulminant myocarditis due to COVID-19 and received intensive care. Even after the acute phase, a skin defect measuring 10 mm × 7 mm was noted, exposing the underlying bone on her right great toe tip. Because of ulceration, she was unable to start walking training. To continue rehabilitation, we reconstructed it with the innerved hemi-pulp V-Y advancement flap. The pain improved quickly, and rehabilitation was resumed. During the 6-month follow-up period, no cosmetic or functional complications were observed. Plantar pressure measurements demonstrated favorable loading on the great toe, and it was a favorable outcome in walking function. This flap is a valuable option as one of the innervated flaps for toe-end necrosis with preserved blood flow, which helps in implementing prompt gait rehabilitation.
Demographic Characteristics, Clinical Presentations, and Risk Factors Impacting Visual Outcomes in Peripheral Ulcerative Keratitis
Authors: Singh Rohan Bir , Atta Sarah , Srikumaran Divya , Jhanji Vishal
Published: March 2024

Purpose:

To assess the demographic characteristics, ophthalmic and systemic presentations, and risk factors impacting the outcomes in patients diagnosed with peripheral ulcerative keratitis (PUK).

Methods:

This retrospective study includes patients diagnosed with PUK at a tertiary care center over 13 years. A descriptive analysis of the demographics, clinical history, and presentation was performed. A reverse risk analysis was performed to assess the PUK resolution in patients with underlying autoimmune and non-autoimmune etiologies. Finally, we evaluated the correlation between treatment duration and final best corrected visual acuity (BCVA) and continuous and categorical variables.

Results:

A total of 58 eyes of 51 patients with a mean age of 59.67 ± 13.41 years diagnosed with PUK were included in the study; 58.82% were female. The resolution duration was significantly shorter in patients with autoimmune etiologies (vs. non-autoimmune etiologies, P = 0.028) and female patients (vs. male patients, P = 0.008). The BCVA worsened in patients with non-autoimmune etiologies after treatment (P = 0.17). Despite worse BCVA at presentation in patients with underlying autoimmune etiologies, significantly better final vision outcomes were observed (P = 0.04). Linear regression analysis showed that longer treatment duration (P = 0.001; R2 = 0.1704) and worse vision (P = 0.002; R2 = 0.1502) at presentation were the primary risk factors of poor vision outcomes. Similarly, the treatment duration was significantly longer in male compared with female patients (P < 0.001; R2 = 0.2027).

Conclusions:

The clinical outcomes in PUK with underlying autoimmune disorders were observed to be better than non-autoimmune etiologies, which may be attributed to the early detection of the PUK-related changes and aggressive medical management. A delayed diagnosis of PUK leads to poor vision outcomes.
Prehabilitation Maximizing Functional Mobility in Patients With Cardiogenic Shock Supported on Axillary Impella
Authors: Bhardwaj Anju , Salas de Armas Ismael A. , Bergeron Amanda , Sauer R. Michelle , Gilley Christa , Reeves Kathryn , Patarroyo-Aponte Maria , Akay Mehmet H. , Patel Manish , Kumar Sachin , Patel Jayeshkumar , Marcano Juan , Nathan Sriram , Gregoric Igor D. , Kar Biswajit
Published: March 2024

Physical therapy (PT) benefits for critically ill patients are well recognized; however, little data exist on PT in patients receiving temporary mechanical circulatory support. In this single-center retrospective study (February 2017–January 2022), we analyzed 37 patients who received an axillary Impella device (Abiomed, Danvers, MA) and PT to “prehabilitate” them before durable left ventricular assist device (dLVAD) implantation. The Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility tool assessed the functional status at different points during admission. Immediately after Impella placement, the median AM-PAC score was 12.7 (interquartile range [IQR], 9–15), and the scores continued to significantly increase to 18.4 (IQR, 16–23) before dLVAD and up to 20.7 (IQR, 19–24) at discharge, indicating improved independence. No PT-related complications were reported. Thus, we hypothesize that critically ill patients initially deemed equivocal candidates may safely participate in PT while maximizing functional activities before dLVAD placement.
Squaring the Circle. Brain death and organ transplantation
Authors: Doyle Howard R.
Published: March 2024

Purpose of review

The adoption of brain death played a crucial role in the development of organ transplantation, but the concept has become increasingly controversial. This essay will explore the current state of the controversy and its implications for the field.

Recent developments

The brain death debate, long limited to the bioethics community, has in recent years burst into the public consciousness following several high-profile cases. This has culminated in the reevaluation of the Uniform Determination of Death Act (UDDA), which is in the process of being updated. Any change to the UDDA has the potential to significantly impact the availability of organs.

The current update to the UDDA introduces an element of uncertainty, one the brain death debate had not previously had.
Thoraco-abdominal normothermic regional perfusion for thoracic transplantation in the United States: current state and future directions
Authors: Bommareddi Swaroop , Lima Brian , Shah Ashish S. , Trahanas John M.
Published: March 2024

Purpose of review

To provide an update regarding the state of thoracoabdominal normothermic regional perfusion (taNRP) when used for thoracic organ recovery

Recent findings

taNRP is growing in its utilization for thoracic organ recovery from donation after circulatory death donors, partly because of its cost effectiveness. taNRP has been shown to yield cardiac allograft recipient outcomes similar to those of brain-dead donors. Regarding the use of taNRP to recover donor lungs, United Network for Organ Sharing (UNOS) analysis shows that taNRP recovered lungs are noninferior, and taNRP has been used to consistently recover excellent lungs at high volume centers. Despite its growth, ethical debate regarding taNRP continues, though clinical data now supports the notion that there is no meaningful brain perfusion after clamping the aortic arch vessels.

taNRP is an excellent method for recovering both heart and lungs from donation after circulatory death donors and yields satisfactory recipient outcomes in a cost-effective manner. taNRP is now endorsed by the American Society of Transplant Surgeons, though ethical debate continues.
Reappraisal of p16 for Determining HPV Status of Head and Neck Carcinomas Arising in HPV Hotspots
Authors: Bhardwaj Swati , Gitman Melissa , Ramirez Juan D. , Paniz-Mondolfi Alberto , Westra William H.
Published: March 2024

In an era of head and neck oncology where HPV status will soon dictate patient management, reliable HPV detection is critical. P16 immunohistochemistry (IHC) is currently recommended as the test of choice for oropharyngeal squamous cell carcinomas (OPSCCs). The purpose of this study was to determine the performance characteristics of p16 IHC based on a large clinical experience of squamous cell carcinomas (SCC) arising from HPV hot-spot regions of the head and neck. Consecutive OPSCCs, sinonasal SCCs, and metastatic SCCs of unknown primary sites were evaluated for the presence of HPV by p16 IHC and PCR-based HPV DNA testing as part of clinical care. For discrepant cases, high-risk HPV E6/E7 mRNA in situ hybridization (ISH) and, when possible, matrix-assisted laser desorption/ionization—time of flight (MALDI-TOF) mass spectrometry (MassArray) genotyping were performed. 746 cancers underwent HPV testing by p16 IHC and DNA PCR genotyping. There was a 95.6% concordance between the 2 assays. Of the 33 discrepant cases, 32 cases (4.3%) were p16 positive but HPV DNA negative. In these cases, 68% were positive for mRNA ISH, invariably related to a non-16 HPV genotype. P16 IHC had an overall accuracy of 98.8%, a sensitivity of 99.8%, and a specificity of 92.1%. P16 IHC is a sensitive and specific assay for determining HPV status. HPV DNA PCR appears vulnerable to HPV genotype diversity and is prone to missing rare non-16 genotypes. HPV mRNA ISH is a practical and reliable direct measure of HPV that may help eliminate the small number of false-positive p16 cases and avoid potential patient harm related to erroneous HPV classification.
Distinctive Pathology Associated With Focal Stenosis of the Main Pancreatic Duct Secondary to Remote Trauma
Authors: Wu Annie A. , Thompson Elizabeth D. , Cameron John L. , He Jin , Burkhart Richard A. , Burns William R. , Lafaro Kelly J. , Shubert Christopher R. , Canto Marcia I. , Fishman Elliot K. , Hruban Ralph H.
Published: March 2024

The radiologic finding of focal stenosis of the main pancreatic duct is highly suggestive of pancreatic cancer. Even in the absence of a mass lesion, focal duct stenosis can lead to surgical resection of the affected portion of the pancreas. We present four patients with distinctive pathology associated with non-neoplastic focal stenosis of the main pancreatic duct. The pathology included stenosis of the pancreatic duct accompanied by wavy, acellular, serpentine-like fibrosis, chronic inflammation with foreign body–type giant cell reaction, and calcifications. In all cases, the pancreas toward the tail of the gland had obstructive changes including acinar drop-out and interlobular and intralobular fibrosis. Three of the four patients had a remote history of major motor vehicle accidents associated with severe abdominal trauma. These results emphasize that blunt trauma can injure the pancreas and that this injury can result in long-term complications, including focal stenosis of the main pancreatic duct. Pathologists should be aware of the distinct pathology associated with remote trauma and, when the pathology is present, should elicit the appropriate clinical history.
A proposal for a simplified measure of HIV preexposure prophylaxis prevention-effective adherence in self-report questionnaires
Authors: Fraser Doug , Holt Martin , Ong Jason J. , Bourne Christopher , Chan Curtis , Grulich Andrew E. , Bavinton Benjamin R.
Published: March 2024

Evaluating HIV preexposure prophylaxis (PrEP) use and HIV risk events concurrently remains challenging. We developed a single question method for measuring prevention-effective adherence with PrEP in self-report questionnaires. In a questionnaire completed by 409 gay and bisexual men, 46% reported condomless anal sex that was not covered by their own PrEP use, and this was more common among younger, lower-income participants. Refining this questionnaire item could improve measurement of prevention-effective adherence.
Evaluation of the Efficacy of Three Times Titanium Plate Gradual Fixation Method in the Treatment of Extracapsular Condylar Fractures
Authors: Wu Shiyan , Zhang Wenbin , Shi Jun
Published: March 2024

Objective:

An improved method of treating inwardly dislocated mandibular extracapsular condylar fracture—three times titanium plate gradual fixation method was introduced, and the clinical efficacy of this method was evaluated.

Methods:

Twenty patients with extracapsular condylar fractures who underwent surgical treatment using the three times titanium plate gradual restoration and fixation method in the Department of Oral Craniomaxillofacial Surgery of the Ninth People’s Hospital of Shanghai from November 2020 to June 2023 were selected as the study subjects.

Results:

After condylar restoration 22 sides reached healing and 1 side was basically healed; in 3 months after the operation, the degree of opening the mouth and the type of the opening of the mouth reached normal, and 1 case had mildly poor occlusion, which required to be further adjusted through orthodontics, and there was no temporomandibular function disorder or facial nerve function damage.

Conclusion:

Three times of gradual fixation with a titanium plate can make the condylar process achieve precise and stable repositioning, and make the surgical process orderly, and it is a kind of reliable fixation method for extracapsular condylar fractures.
A Comparison of U.S. Individual and Family Plan Medication Coverage for Overactive Bladder
Authors: Gaddam Neha G. , Wallace Megan B. , Dieter Alexis A.
Published: March 2024

Importance

There is strong evidence for long-term cognitive effects with anticholinergic use. Differences in insurance coverage of anticholinergics and beta-3 agonists hinder individualization of overactive bladder (OAB) treatment.

Objectives

The aims of the study were to assess individual and family health insurance plan coverage for select OAB medications and to compare coverage of preferred medications to those with a greater risk of cognitive dysfunction.

Study Design

This cross-sectional study analyzed formularies for the top 7 U.S. medical insurers. Coverage tiers were assessed for the following 7 OAB medications: (1) oxybutynin instant-release 5 mg, (2) oxybutynin extended-release 5 mg, (3) solifenacin 5 mg, (4) trospium instant-release 20 mg, (5) trospium extended-release 60 mg, (6) mirabegron 25 mg, and (7) vibegron 75 mg. Coverage was compared between nonpreferred (oxybutynin, solifenacin) and preferred medications (trospium, mirabegron, vibegron). Coverage scores, representing a weighted average based on coverage tier frequency relative to the number of plans investigated for each state or insurer, were generated with a lower coverage score indicating better coverage (range, 0.2–1.0).

Results

A total of 2,780 insurance plans from 41 states representing a 47% market share for the individual and family marketplace were evaluated. Oxybutynin IR had the best coverage score across insurers (0.2) while vibegron had the worst (0.92). Preferred medications were more often designated to higher tiers with worse coverage compared with nonpreferred medications (P< 0.001). Less concordance in coverage between insurers was noted for anticholinergics with greater bladder specificity and for extended-release formulations.

Conclusions

Despite risks with anticholinergics, beta-3 agonists were more expensive across all insurers highlighting the need for expanded coverage of preferred medications to avoid cognitive dysfunction when undergoing treatment for OAB.