bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymptotic Weak Gravity Conjecture in M-theory on K3× K3
Authors: Charkaoui M , Sammani R , Saidi E H , Laamara R Ahl
Published: June 2024

The Asymptotic Weak Gravity Conjecture (WGC) has been proposed as a special case of the Tower WGC that probes infinite distances in the moduli space corresponding to weakly coupled gauge regimes. The conjecture has been studied in M-theory on a Calabi–Yau threefold (CY3) with finite volume inducing a 5D effective quantum field theory. In this paper, we extend the scope of the previous study to encompass lower dimensions, particularly we generalize the obtained 5D Asymptotic WGC to the effective field theory (EFT$_{3D}$) coupled to 3D gravity that descends from M-theory compactified on a Calabi–Yau fourfold with an emphasis on $K3\times K3$. We find that the CY4 has three fibration structures labeled as line Type-$\mathbb {T}^{2}$, surface Type-$\mathbb {S}$, and bulk Type-$\mathbb {V}$. The emergent EFT$_{3D}$ is shown to have 2+2 towers of particle states termed as the BPS $\mathcal {T}_{M_{\mathrm{k}}\rightarrow 0}^{\rm{{\small BPS}}}$ and $\mathcal {T}_{M_{\mathrm{k}}\rightarrow \infty }^{\rm{{\small BPS}}}$ as well as the non-BPS $\mathcal {T}_{M_{\mathrm{k}}\rightarrow 0}^{\rm{{\small N-BPS}}}$ and $\mathcal {T}_{M_{\mathrm{k}}\rightarrow \infty }^{\rm{{\small N-BPS}}}$. To ensure the viability of the 3D Asymptotic WGC, we give explicit calculations to thoroughly test the Swampland constraint for both the weakly and strongly gauge coupled regimes. Additional aspects, including the gauge symmetry breaking and duality symmetry, are also investigated.
Firm Networks and Asset Returns
Authors: Ramírez Carlos A
Published: June 2024

Changes in the propagation of shocks along firm networks are important to understanding aggregate and cross-sectional features of stock returns. When calibrated to match key characteristics of supplier–customer networks in the United States, a model in which firms are interlinked via enduring relationships generates long-run consumption risks, high and volatile risk premiums, and a small and stable risk-free rate. The model also matches cross-sectional patterns of portfolio returns sorted by firm centrality, a feature unaccounted for by standard asset pricing models. (JEL C67, E30, G12, L14)
The Managerial Family? Family Care Work in Germany and Spain
Authors: Lüth Laura , Zimmermann Katharina
Published: June 2024

This article engages with scholarly debates on the emergence of market logics in family life. By deploying qualitative data from couple interviews in Germany and Spain, we show how the existence of a so-called managerial family is salient among interviewees in both countries. Couples might introduce weekly family planning meetings or follow investment strategies when organizing childcare and housework. Drawing on the theoretical concept of moral economies, the article adds a macro-level institutional perspective to this picture of entrepreneurial family life by linking how couples justify their managerial practices to macro-level moral ideas and the institutional setup in which they live.
Investigation of the diversity, equity, inclusion, and belonging within the undergraduate student population within the Department of Animal Science at Iowa State University
Authors: Carlson Kelsi A , Bundy Jennifer M , Martin Michael J , Smalley Scott W , Johnson Anna K
Published: June 2024

Iowa State University (ISU) provides resources for diversity, equity, inclusion, and belonging (DEI-B) to provide students with a comfortable academic home regardless of their demographics or prior experiences. The objective of this study was to investigate undergraduate students’ DEI-B perspectives in the Department of Animal Science at ISU. One survey instrument was developed containing 14 questions that covered demographics, feelings of inclusion, comfort-seeking tools, and ways to improve DEI-B. Answer choices were either multiple choice, 1 to 5 sliding scale, or a specified text sliding scale. Eligible participants were undergraduate students enrolled in Animal or Dairy Science (n = 974). Demographics and comfort-seeking tools will be presented descriptively. Inclusion at the start and after 2 yr were compared using six different linear models. A variable was deemed significant if the P-value was ≤ 0.05. A total of 383 students (88% of total respondents) completed 50% or more of the inclusion questions. Seniors had the highest response rate. More students reported coming from a rural background. Primary species of interest was companion animals. There were no observed differences in feelings of inclusion in classes, with peers, or with faculty for hometown, admission type, ethnic group, and first generation when students started (P ≥ 0.067). There was a difference for primary species of interest (P ≤ 0.011) and with female students feeling less included (P ≤ 0.039). There were no observed differences after 2 yr in classes, with peers, or with faculty for classification year, admission type, or first generation (P ≥ 0.088). Suburban students felt the least included in classes compared to rural and urban students (P ≤ 0.036). Female students felt less included in all three categories (P ≤ 0.017). The majority of students reported having companion animal experience but almost half reported having no experience with livestock prior to ISU. A total of 51% of students said they never considered transferring to another major and 48% indicated that they plan to pursue a career in veterinary medicine. A total of 75% of students felt inclusion could be improved by creating more hands-on opportunities and 60% suggested the department provide more study space. In conclusion, the Department of Animal Science at ISU has some effective inclusion practices but needs to evolve and improve in its DEI-B practices for the undergraduate student population.
Chromatographic purification of the plasmin‐like enzyme from clamworm (Perinereis aibuhitensis Grub) and its fibrinolytic activity by metal ions
Authors: Song Tuo , Han Xinyuan , Jiang Tingting , Pu Xinyi , Wei Mingjun , Zhu Yuping , Wu Wenhui
Published: June 2024

In this study, fibrinolytic protease was isolated and purified from Perinereis aibuhitensis Grub, and the extraction process was optimized. The properties of the enzyme, such as the amino acid composition, thermal stability, optimal temperature, and pH, were investigated. After detoxification, proteins collected from fresh Clamworm (Perinereis aibuhitensis Grub) were concentrated via ammonium sulfate precipitation. The crude protease was purified using gel filtration resin (Sephadex G‐100), anion exchange resin (DEAE‐Sepharose FF), and hydrophobic resin (Phenyl Sepharose 6FF). The molecular weight of the protease was determined by polyacrylamide gel electrophoresis (SDS‐PAGE). The optimum temperature and optimum pH of the protease were determined. The activity of crude protease in the 40–60% salt‐out section was the highest, reaching 467.53 U/mg. The optimal process for purifying crude protein involved the application of DEAE‐Sepharose FF and Phenyl Sepharose 6FF, which resulted in the isolation of a single protease known as Asp60‐D1‐P1 with the highest fibrinolytic activity; additionally, the enzyme activity was measured at 3367.76 U/mg. Analysis by Native‐PAGE and SDS‐PAGE revealed that the molecular weight of Asp60‐D1‐P1 was 44.5 kDa, which consisted of two subunits with molecular weights of 6.5 and 37.8 kDa, respectively. The optimum temperature for Asp60‐D1‐P1 was 40°C, and the optimal pH was 8.0.
Treatment options in refractory chronic spontaneous urticaria
Authors: Pathania Yashdeep Singh
Published: June 2024

Purpose of review

Chronic spontaneous urticaria (CSU) patients sometimes do not respond to second-generation antihistamine, and 10–50% patients do not even respond to four-fold the usual dose of nonsedating H1 antihistamine, which further leads to repeated courses of oral corticosteroids to abate the symptoms. There are third-line agents approved by EAACI guidelines, which include omalizumab and cyclosporine. Certain patients are even resistant to the third-line agents. In this review, various other treatment options will be discussed in patients of refractory CSU.

Recent findings

Recently, we demonstrated azathioprine as a possible third-line option, which was found noninferior to cyclosporine in antihistamine refractory CSU. There have been trials, studies, case series and reports, which suggest other putative options for refractory CSU management.

Studies on the management of refractory CSU are accumulating thereby expanding the armamentarium of dermatologists and allergologist against difficult-to-treat urticaria patients.
Reimagining Initial Certification as a Process That Begins During Residency to Support Continuous Development Across Training and Practice
Authors: Carraccio Carol , Schumacher Daniel J. , ten Cate Olle
Published: June 2024

In the United States, initial board certification remains focused on a high-stakes knowledge examination after completion of training. A more contemporary view supports a program of assessment that includes multiple types and sources of data with an emphasis on direct workplace observation to get the best picture of an individual’s performance. In this article, the authors reimagine initial certification as a continuous assessment for learning that begins in residency, focuses on both knowledge acquisition and its application, and interdigitates intentionally with the first cycle of maintenance of certification to advance learning and smooth the transition from training to practice. A more expanded view of competence, as a 3-layered construct (canonical, contextual, and personalized), supports this proposal. Canonical competence (context-independent knowledge)—best assessed through examinations of knowledge—is most heavily weighted and assessed during medical school but remains critical throughout one’s career. Contextual competence (context-dependent knowledge) is best assessed in the workplace and is key during residency and fellowship as trainees navigate a myriad of clinical work environments. Personalized competence, representing the totality of one’s unique areas of expertise, is best demonstrated during the practice years when deliberate practice experience supports the growth of personalized expertise and discoveries that advance the field. Shifting initial board certification from relying on an anxiety-provoking, high-stakes, often single moment in time-standardized examination to a nuanced approach that is part of an individual trainee’s program of assessment offers a more just and robust decision about readiness for unsupervised practice. Such a model would also sow the seeds of meaningful individualization of learning needs that begins in training, continues through practice, and lays the foundation for improving the quality of care for patients within a given practice as well as shifting the current contiguous phases of training and practice into a true continuum.
Current management of giant cell arteritis and its complications
Authors: Galli Elena , Muratore Francesco , Warrington Kenneth J.
Published: June 2024

Purpose of the review

This review provides an update on current management strategies for giant cell arteritis (GCA), emphasizing the need for alternative therapies to reduce disease relapses and mitigate glucocorticoid (GC)-related morbidity.

Recent Findings

The standard of care for GCA has traditionally involved prolonged use of GC, and recent studies are exploring faster GC tapering regimens in an effort to reduce adverse effects while maintaining disease control. Randomized clinical trials have highlighted the efficacy of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, in reducing disease flares and sparing GCs. However, the optimal treatment duration with TCZ is unknown and patients remain at risk of relapse after treatment discontinuation. An unmet therapeutic need persists for patients who are not candidates for TCZ, and for those who have inadequate response to this biologic. Therefore, investigations into alternative therapies such as targeting interleukin-17A, blocking T-cell activation or inhibiting the Janus kinase–signal transducer and activator of transcription pathway, showcase potential avenues for tailored treatments.

While GCs remain the cornerstone of therapy, TCZ emerges as a promising GC-sparing agent. Ongoing research targeting different pathways implicated in GCA pathogenesis have led to encouraging results. However, the preliminary nature of these findings necessitates larger randomized controlled trials to establish their efficacy conclusively.
Accuracy of Phantomless Calibration of Routine Computed Tomography Scans for Opportunistic Osteoporosis Screening in the Spine Clinic
Authors: Cetik Riza M. , Crawford Charles H. , Glassman Steven D. , Dimar John R. , Gum Jeffrey L. , Djurasovic Mladen , Carreon Leah Y.
Published: June 2024

Study Design.

Diagnostic accuracy study

Objective.

To establish a simple method of phantomless bone mineral density (BMD) measurement by using preoperative lumbar Computed Tomography (CT) scans, and compare the accuracy of reference tissue combinations to diagnose low BMD against uncalibrated Hounsfield units (HUs).

Summary of Background Data.

HUs are used as a measure of BMD; however, associations between HU and T-scores vary widely. Quantitative CT (qCT) scans are more accurate, but they require density calibration with an object of known density (phantom), which limits feasibility. As an emerging technique, phantomless (internal) calibration of routine CT scans may provide a good opportunity for screening.

Methods.

Patients who were scheduled to undergo lumbar surgery, with a preoperative CT scan, and a dual-energy x-ray absorptiometry (DXA) scan within six months were included. Four tissues were selected for calibration: subcutaneous adipose (A), erector spinae (ES), psoas (P) and aortic blood (AB). The HUs of these tissues were used in linear regression against ground-truth values. Calibrations were performed by using two different internal tissues at a time to maintain simplicity and in-office applicability.

Volumetric bone mineral densities (vBMD) derived from internally calibrated CT scans were analyzed for new threshold values for low bone density. Areas under the curve (AUC) were calculated with 95% confidence intervals (CI).

Results.

45 patients were included (M/F=10/35, mean age:63.3). Calibrated vBMDs had stronger correlations with DXA T-scores when compared with HUs, with L2 exhibiting the highest coefficients. Calibration by using A and ES with the threshold of 162 mg/cm3 had a sensitivity of 90% in detecting low BMD (AUC=0.671).

Conclusions.

This novel method allows simple, in-office calibration of routine preoperative CT scans without the use of a phantom. Calibration using adipose and erector spinae with a threshold of 162 mg/cm3 is proposed for low bone density screening with high sensitivity (90%).

Level of Evidence.

Level III
Kidney Outcomes and Trajectories of Tubular Injury and Function in Critically Ill Patients With and Without COVID-19
Authors: Granda Michael L. , Tian Frances , Zelnick Leila R. , Bhatraju Pavan K. , Hallowell Julia , Wurfel Mark M. , Hoofnagle Andrew , Morrell Eric , Kestenbaum Bryan
Published: June 2024

IMPORTANCE:

COVID-19 may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked contemporaneous controls or measured kidney biomarkers at a single time point.

OBJECTIVES:

To better understand mechanisms of acute kidney injury in COVID-19, we compared kidney outcomes and trajectories of tubular injury, viability, and function in prospectively enrolled critically ill adults with and without COVID-19.

DESIGN, SETTING, AND PARTICIPANTS:

The COVID-19 Host Response and Outcomes study prospectively enrolled patients admitted to ICUs in Washington State with symptoms of lower respiratory tract infection, determining COVID-19 status by nucleic acid amplification on arrival.

MAIN OUTCOMES AND MEASURES:

We evaluated major adverse kidney events (MAKE) defined as a doubling of serum creatinine, kidney replacement therapy, or death, in 330 patients after inverse probability weighting. In the 181 patients with available biosamples, we determined trajectories of urine kidney injury molecule-1 (KIM-1) and epithelial growth factor (EGF), and urine:plasma ratios of endogenous markers of tubular secretory clearance.

RESULTS:

At ICU admission, the mean age was 55 ± 16 years; 45% required mechanical ventilation; and the mean serum creatinine concentration was 1.1 mg/dL. COVID-19 was associated with a 70% greater occurrence of MAKE (relative risk 1.70; 95% CI, 1.05–2.74) and a 741% greater occurrence of KRT (relative risk 7.41; 95% CI, 1.69–32.41). The biomarker cohort had a median of three follow-up measurements. Urine EGF, secretory clearance ratios, and estimated glomerular filtration rate (eGFR) increased over time in the COVID-19 negative group but remained unchanged in the COVID-19 positive group. In contrast, urine KIM-1 concentrations did not significantly change over the course of the study in either group.

CONCLUSIONS:

Among critically ill adults, COVID-19 is associated with a more protracted course of proximal tubular dysfunction and reduced eGFR despite similar degrees of kidney injury.
Child Opportunity Index and Pediatric Extracorporeal Membrane Oxygenation Outcomes; the Role of Diagnostic Category
Authors: Alizadeh Faraz , Gauvreau Kimberlee , Barreto Jessica A. , Hall Matt , Bucholz Emily , Nathan Meena , Newburger Jane W. , Vitali Sally , Thiagarajan Ravi R. , Chan Titus , Moynihan Katie M.
Published: June 2024

OBJECTIVES:

To study the impact of social determinants of health (SDoH) on pediatric extracorporeal membrane oxygenation (ECMO) outcomes.

DESIGN, SETTING, AND PATIENTS:

Retrospective study of children (< 18 yr) supported on ECMO (October 1, 2015 to March 1, 2021) using Pediatric Health Information System (44 U.S. children’s hospitals). Patients were divided into five diagnostic categories: neonatal cardiac, pediatric cardiac, neonatal respiratory, pediatric respiratory, and sepsis. SDoH included the Child Opportunity Index (COI; higher indicates social advantage), race, ethnicity, payer, and U.S. region. Children without COI were excluded. Diagnostic category-specific clinical variables related to baseline health and illness severity were collected.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Children supported on ECMO experienced a 33% in-hospital mortality (2863/8710). Overall, children with lower COI, “other” race, Hispanic ethnicity, public insurance and from South or West regions had greater mortality. Associations between SDoH and ECMO outcomes differed between diagnostic cohorts. Bivariate analyses found that only pediatric cardiac patients had an association between COI or race and mortality. Multivariable logistic regression analyses examined relationships between SDoH, clinical variables and mortality within diagnostic categories. Pediatric cardiac patients had 5% increased odds of death (95% CI, 1.01–1.09) for every 10-point decrement in COI, while Hispanic ethnicity was associated with higher survival (adjusted odds ratio [aOR] 0.72 [0.57–0.89]). Children with heart disease from the highest COI quintile had less cardiac-surgical complexity and earlier cannulation. Independent associations with mortality were observed in sepsis for Black race (aOR 1.62 [1.06–2.47]) and other payer in pediatric respiratory patients (aOR 1.94 [1.23–3.06]).

CONCLUSIONS:

SDoH are statistically associated with pediatric ECMO outcomes; however, associations differ between diagnostic categories. Influence of COI was observed only in cardiac patients while payer, race, and ethnicity results varied. Further research should investigate differences between diagnostic cohorts and age groups to understand drivers of inequitable outcomes.
Trends in diffuse type of gastric cancer: focus on younger women
Authors: Corso Giovanni , Santucci Claudia , Toffolutti Federica , Pisa Eleonora , La Vecchia Carlo , Serraino Diego
Published: June 2024

Background

Gastric cancer (GC) incidence has been decreasing over the last decades; however, there are uncertainties in trends and proportional distribution of the diffuse type.

Methods

GC incidence data were extracted from the population-based Friuli Venezia Giulia Cancer Registry. GC types (diffuse vs. others) were compared in relation to age at diagnosis, calendar years, and sexes.

Results

Between 1995 and 2021, diffuse GC accounted for 10.2% of all GCs. The proportion was greater among individuals aged <45 years, 34.0% in women and 25.7% in men. An increasing proportion over time was observed, in particular in women (from 9.9% in 1995–2000 to 14.10% during 2011–2021). In the last decade (2011–2021), a decreased incidence of all GC was observed, reaching an age-standardized rate (world standard) of 1.4/100,000 for men and 1.2/100,000 for women. Rates of diffuse GC were 0.3/100,000 in younger population.

Conclusion

Although the overall GC incidence is decreasing, the percentage of diffuse GC is increasing in the younger population, particularly in women. Reasons for the increased proportion of diffuse-type GC within younger women remain uncertain, possibly related to the decreased exposure to risk factors for other GC histotypes.
Onychomatricomas: Assessing Surgical Outcomes
Authors: van de Borne Laura , Costantini Mathilde , Dehavay Florence , Richert Bertrand
Published: June 2024

BACKGROUND

Onychomatricoma (OM) is a rare benign tumor of the nail matrix. Treatment is surgical, but data are currently limited.

OBJECTIVE

To review all cases of OM operated in their department and to assess the link between the location on the nail plate, the thickness and width of the lesion, and the postoperative outcomes.

MATERIALS AND METHODS

Records of 62 patients were retrieved from their department's database over a 25-year period (1998–2023).

RESULTS

Of the 62 patients, 41 were eligible. In total, 58% of OM occupied a width of a quarter of the nail plate, 51% had a plate thinner than 3 mm, and 51% were laterally located. Of the 41 patients included, 29 had a tangential excision and 12 underwent lateral longitudinal excision. Among the tangential excision group, 71% had normal nail regrowth. Onychomatricoma thicker than 3 mm and involving the total nail plate width had a sequelae in 60% of cases.

CONCLUSION

Tangential excision of onychomatricomas allows a normal nail regrowth in 71% of cases. The risk of sequelae increases for tumors thicker than 3 mm and involving the total nail plate width. Medial or lateral location seems to have no influence.
Therapeutic manipulation of the microbiome in liver disease
Authors: Parthasarathy Gopanandan , Malhi Harmeet , Bajaj Jasmohan S.
Published: June 2024

Myriad associations between the microbiome and various facets of liver physiology and pathology have been described in the literature. Building on descriptive and correlative sequencing studies, metagenomic studies are expanding our collective understanding of the functional and mechanistic role of the microbiome as mediators of the gut-liver axis. Based on these mechanisms, the functional activity of the microbiome represents an attractive, tractable, and precision medicine therapeutic target in several liver diseases. Indeed, several therapeutics have been used in liver disease even before their description as a microbiome-dependent approach. To bring successful microbiome-targeted and microbiome-inspired therapies to the clinic, a comprehensive appreciation of the different approaches to influence, collaborate with, or engineer the gut microbiome to coopt a disease-relevant function of interest in the right patient is key. Herein, we describe the various levels at which the microbiome can be targeted—from prebiotics, probiotics, synbiotics, and antibiotics to microbiome reconstitution and precision microbiome engineering. Assimilating data from preclinical animal models, human studies as well as clinical trials, we describe the potential for and rationale behind studying such therapies across several liver diseases, including metabolic dysfunction–associated steatotic liver disease, alcohol-associated liver disease, cirrhosis, HE as well as liver cancer. Lastly, we discuss lessons learned from previous attempts at developing such therapies, the regulatory framework that needs to be navigated, and the challenges that remain.
Documenting Compliance and Symptom Reactivity for Ambulatory Assessment Methodology Following Concussion in Adolescents and Young Adults: Feasibility of the Mobile Neurocognitive Health (MNCH) Project
Authors: Elbin R. J. , Durfee Kori J. , Womble Melissa N. , Jennings Sabrina , Fedor Sheri , Dollar Christina M. , Felt John M. , Elbich Daniel B. , Hakun Jonathan G.
Published: June 2024

Objective:

Evaluate compliance, symptom reactivity, and acceptability/experience ratings for an ecological momentary assessment (EMA) protocol involving ultra-brief ambulatory cognitive assessments in adolescent and young adult patients with concussion.

Setting:

Outpatient concussion clinic.

Participants:

116 patients aged 13 to 25 years with concussion.

Design:

Prospective research design was used to examine compliance, symptom reactivity, and acceptability/experience for the Mobile Neurocognitive Health Project (MNCH); an EMA study of environmental exposures, symptoms, objective cognitive functioning, and symptom reactivity involving 4, daily EMA surveys (7:30 am, 10:30 am, 3:00 pm, 8:00 pm) for a period of 7 days following concussion. Overall compliance rates, symptom reactivity scores, and participant acceptability/experience ratings were described. A series of non-parametric Friedman Tests with post-hoc Wilcoxon signed-rank tests were used to examine differences in compliance and reactivity related to time of day and over the course of the protocol (first 3 days [Early Week] vs last 4 days [Late Week]).

Main Measures:

Compliance rates, symptom reactivity scores, participant experience/acceptability.

Results:

Overall median compliance was 71%, and there were significantly fewer 7:30 am surveys completed compared to the 10:30 am (Z = −4.88,P ≤ .001), 3:00 pm (Z = −4.13,P ≤ .001), and 8:00 pm (Z = −4.68, P ≤ .001) surveys. Compliance for Early Week surveys were significantly higher than Late Week (Z = −2.16,P = .009). The median symptom reactivity score was 34.39 out of 100 and was significantly higher for Early Week compared to Late Week (Z = −4.59,P ≤ .001). Ninety-nine percent (89/90) of the sample agreed that the app was easy to use, and 18% (16/90) indicated that the app interfered with their daily life.

Conclusion:

Adolescents and young adults with concussion were compliant with the MNCH EMA protocol. Symptom reactivity to the protocol was low and the majority of participants reported that the app and protocol were acceptable. These findings support further investigation into applications of EMA for use in concussion studies.
Evaluation of Anti-Glycopeptidolipid-Core Immunoglobulin A Antibody Detection for the Diagnosis of Nontuberculous Mycobacterial Cervicofacial Lymphadenitis
Authors: Willemse Samuel H. , Oomens Marjolijn A.E.M. , Karssemakers Luc H.E. , Lindeboom Jerome A. , Schreuder Willem H. , Ho Jean-Pierre T.F. , van der Kuip Martijn , Vlaming Killian E. , Kaptein Tanja M. , de Lange Jan
Published: June 2024

A multicenter cross-sectional diagnostic study was carried out including 45 children with nontuberculous mycobacterial cervicofacial lymphadenitis and controls. The tested immunoassay, detecting M. avium–specific anti-glycopeptidolipid-core immunoglobulin A antibodies, had inadequate diagnostic performance in the studied population and seems to be of no additional value in detecting cases of nontuberculous mycobacterial cervicofacial lymphadenitis.
RSV in Young Children During and After the COVID-19 Pandemic—Implications for Delaying the Age of First Infection
Authors: Hancock Zoe , Muir Peter , North Paul , Williams Philip , Veasey Nicholas , Finn Adam , Marlow Robin
Published: June 2024

Nonpharmaceutical interventions introduced in the United Kingdom’s response to the COVID-19 pandemic disrupted the transmission of other childhood infections. We report changes in seasonality, age dynamics and severity of respiratory syncytial virus infections between 2019 and 2023. These data show the potential effects of delaying respiratory syncytial virus exposure and may provide insights for the implementation of treatments preventing infection during early infancy.
Possible involvement of satellite glial cell–derived lipocalin-2 in dermatitis not itch-related behavior of atopic dermatitis model mice
Authors: Takahashi Nobuaki , Tominaga Mitsutoshi , Kamata Yayoi , Takamori Kenji
Published: June 2024

Introduction:

Atopic dermatitis (AD) is a chronic inflammatory skin disease with intractable itch. Dorsal root ganglion (DRG) plays an important role in signal transduction of itch. It has been reported that satellite glial cells (SGC) present around DRG neurons are involved in pain and itch through interactions with DRG neurons. However, it is unclear what factors in SGC are involved in inducing dermatitis and itch in DRG. In this study, we found that the expression of lipocalin-2 (LCN2) was increased in SGC of AD model NC/Nga mouse. Therefore, we also examined whether SGC-derived lipocalin-2 is involved in the induction of dermatitis and itch-related behavior in this model mice.

Materials and methods:

AD-like dermatitis was induced by the application of Dermatophagoides farinae body ointment to NC/Nga mice (AD-NC/Nga mice). Protein and gene expression in the DRG and spinal cord of AD-NC/Nga mice were examined. The effect of the LCN2 antibody on dermatitis pathology in AD-NC/Nga mice was confirmed.

Results:

LCN2 expression in DRG of AD-NC/Nga mice was higher than that of control NC/Nga mice. Immunohistochemical analysis revealed that LCN2 was expressed on SGC in DRG. Gene expression level of LCN2 in the DRG was significantly increased faster than in the spinal cord during the process of induction of AD-like dermatitis. LCN2 increased gene expression of MMP-9 in mouse DRG. Intrathecally administrated anti-LCN2 antibody twice a week for 3 weeks at the same time as induction of AD-like dermatitis reduced dermatitis score without inhibiting scratching behavior.

Discussion:

In conclusion, our data suggest that SGC-derived LCN2 is involved in the pathogenesis of dermatitis rather than itch-related behavior in AD-NC/Nga mice.
Prediction of sepsis among patients with major trauma using artificial intelligence: a multicenter validated cohort study
Authors: Sun Baisheng , Lei Mingxing , Wang Li , Wang Xiaoli , Li Xiaoming , Mao Zhi , Kang Hongjun , Liu Hui , Sun Shiying , Zhou Feihu
Published: June 2024

Background:

Sepsis remains a significant challenge in patients with major trauma in the ICU. Early detection and treatment are crucial for improving outcomes and reducing mortality rates. Nonetheless, clinical tools for predicting sepsis among patients with major trauma are limited. This study aimed to develop and validate an artificial intelligence (AI) platform for predicting the risk of sepsis among patients with major trauma.

Patients and methods:

This study involved 961 patients, with a prospective analysis of data from 244 patients with major trauma at our hospital and a retrospective analysis of data from 717 patients extracted from a database in the United States. The patients from our hospital constituted the model development cohort, and the patients from the database constituted the external validation cohort. The patients in the model development cohort were randomly divided into a training cohort and an internal validation cohort at a ratio of 8:2. The machine-learning algorithms used to train models included logistic regression, decision tree, extreme gradient boosting machine (eXGBM), neural network (NN), random forest, and light gradient boosting machine (LightGBM).

Results:

The incidence of sepsis for the model development cohort was 43.44%. Twelve predictors, including gender, abdominal trauma, open trauma, red blood cell count, heart rate, respiratory rate, injury severity score, sequential organ failure assessment score, Glasgow coma scale, smoking, total protein concentrations, and hematocrit, were used as features in the final model. Internal validation showed that the NN model had the highest area under the curve (AUC) of 0.932 (95% CI: 0.917–0.948), followed by the LightGBM and eXGBM models with AUCs of 0.913 (95% CI: 0.883–0.930) and 0.912 (95% CI: 0.880–0.935), respectively. In the external validation cohort, the eXGBM model (AUC: 0.891, 95% CI: 0.866–0.914) had the highest AUC value, followed by the LightGBM model (AUC: 0.886, 95% CI: 0.860–0.906), and the AUC value of the NN model was only 0.787 (95% CI: 0.751–0.829). Considering the predictive performance for both the internal and external validation cohorts, the LightGBM model had the highest score of 82, followed by the eXGBM (81) and NN (76) models. Thus, the LightGBM has emerged as the optimal model, and it was deployed online as an AI application.

Conclusions:

This study develops and validates an AI application to effectively assess the susceptibility of patients with major trauma to sepsis. The AI application equips healthcare professionals with a valuable tool to promptly identify individuals at high risk of developing sepsis. This will facilitate clinical decision-making and enable early intervention.
Comparison of long-term survival of neoadjuvant therapy plus surgery versus upfront surgery and the role of adjuvant therapy for T1b-2N0-1 esophageal cancer: a population study of the SEER database and Chinese cohort
Authors: Xia Lingling , Shi Wei , Cai Yuxin , Liao Zhengkai , Huang Zhen , Qiu Hu , Wang Jing , Chen Yongshun
Published: June 2024

Background:

For stage T1b-2N0-1 esophageal cancer, the impact of neoadjuvant therapy plus surgery (NS), surgery alone (SA), and surgery plus adjuvant therapy (ST) on cancer-specific survival (CSS) and overall survival (OS) is uncertain.

Methods:

Stage T1b-2N0-1 esophageal cancer patients from the SEER database and two Chinese cancer centers were included in this study. The Kaplan–Meier method was used to plot survival curves, which were compared using the log-rank test. Propensity score matching was used to equalize differences between the groups. Cox proportional hazards regression models were used to analyze prognostic factors. A nomogram for OS was developed after screening the variables using the Cox proportional hazards regression model and the least absolute shrinkage and selection operator. The performance of the nomogram was assessed by the Harrell concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic curve, calibration plots, and decision curve analysis.

Results:

After propensity score matching analysis, the 3-year CSS and OS rates in the NS group compared to the SA group were 80.3% versus 62.1% (P=0.016) and 75.8% versus 55.5% (P=0.006), the 3-year CSS and OS rates in the NS group compared to the ST group were 71.3% versus 68.3% (P=0.560) and 69.8% versus 62.9% (P=0.330), the 3-year CSS and OS rates in the SA group compared to the ST group were 54.6% versus 66.7% (P=0.220) and 50.2% versus 57.9% (P=0.290), respectively. The predictive nomogram for OS in T1b-2N0-1 patients ultimately incorporated five clinicopathological variables: T stage, N stage, age, examined lymph nodes, and therapy modality. The nomogram C-index for predicting OS was 0.648, 0.663, and 0.666 in the training group, external validation group-1, and external validation group-2, respectively. The 1-year, 3-year, and 5-year predicted AUC values of the OS prediction model were 0.659, 0.639, and 0.612 for the training group, and 0.786, 0.758, and 0.692 for validation group-1, and 0.805, 0.760, and 0.693 for validation group-2, respectively.

Conclusion:

For patients with stage T1b-2N0-1 esophageal cancer, neoadjuvant therapy significantly improves prognosis compared to surgery alone, those presenting with positive lymph nodes after upfront surgery can achieve survival benefits from adjuvant therapy.
Simulator Verification Is Potentially Beneficial for the Fitting of Softband Bone Conduction Hearing Devices in Young Children
Authors: Sun Le , Ping Lu , Fan Xinmiao , Wang Jian , Chen Xiaowei
Published: June 2024

Hypothesis

The current study employed a skull-simulator verification method to assess whether the output of softband bone conduction hearing devices (BCHDs) at the manufacturer's default settings deviated widely from the target determined by the fitting formula.

Background

Real ear analysis is utilized for the verification of the fitting of air conduction hearing devices (ACHDs) in a variety of institutions. This procedure, however, has not been used in the fitting of BCHDs, largely due to the difficulty of testing the output of these devices to temporal bones. Despite the availability of skull simulators, they have not been utilized clinically to measure BCHD output.

Materials and Methods

This prospective, single-center study enrolled 42 subjects, aged 3 months to 10 years, with microtia-atresia–associated mild-to-severe bilateral conductive hearing loss. Hearing sensitivity was evaluated behaviorally by pure tone audiometry (PTA) in 22 subjects 4 years or older (the PTA group), and by auditory brainstem response (ABR) in 20 subjects younger than 4 years (the ABR group). Following 6 months of subjects wearing the prescribed softband BCHDs, their dial level (DL) thresholds were reassessed while using their own BCHDs, configured with zero gain across all frequencies, functioning solely as a bone vibrator. These DL thresholds were inputted into the fitting formula, desired sensation level–bone conduction devices (DSL-BCD) for children, to obtain the target values of BCHD output. The simulator output of the BCHD programmed at the manufacturer's default setting was measured in response to speech presented at 55, 65, and 80 dB SPL, followed by gain adjustment based on the differences between the simulator output and the target. Aided speech intelligibility index (SII) was measured before and after the gain adjustment.

Results

The softband BCHDs at the manufacturer's settings generally had lower output than the prescribed target values. This difference was larger at low frequencies and low levels. Across the 12 points tested (four frequencies from 500 to 4000 Hz multiplied by three levels), 22 (52.3%) and 42 (100%) BCHDs had deviations of +7 and +5 dB, respectively, at one point or more. The gain adjustments reduced the deviation and improved the SII values at the two lower levels of speech presented.

Conclusion

The simulator output of softband bone conduction hearing devices (BCHDs) with the manufacturer's settings may exhibit significant deviations from the formula. Objective output verification should be considered a beneficial step in BCHD fitting and is recommended when applicable.
The Role of Asymmetry Values, Gain, and Pathological Saccades of the Video Head Impulse Test (vHIT) in Sudden Sensorineural Hearing Loss
Authors: Qian Yi , Kang Houyong , Zhong Shixun , Tao Chen , Zuo Wenqi , Lei Yan , Jiang Lizhu
Published: June 2024

Objective

The purpose of this study was to evaluate the value of asymmetry values, gain, and pathological saccades of the video head impulse test (vHIT) in sudden sensorineural hearing loss (SSNHL).

Study Design

Retrospective study.

Setting

Tertiary referral center.

Patients

A total of 226 individuals diagnosed with unilateral definite SSNHL were hospitalized. The assessment included a comprehensive evaluation of medical history, pure-tone test, acoustic impedance, positional test, video nystagmography (VNG), vHIT, vestibular evoked myogenic potentials (VEMPs) and magnetic resonance.

Interventions

vHIT, VNG, cVEMP, oVEMP. Statistical analysis was performed with SPSS version 22.0 for Windows.

Main Outcome Measures

The asymmetry values, gain, and pathological saccades of the vHIT.

Results

The abnormal gain of vHIT in anterior, horizontal, and posterior canal in SSNHL patients with vertigo were revealed in 20 of 112 (17.9%), 24 of 112 (21.4%), and 60 of 112 (53.6%), respectively. The vHIT pathological saccades (overt + covert) of anterior, horizontal, and posterior canal in SSNHL patients with vertigo were observed in 5 of 112 (4.6%), 52 of 112 (46.4%), and 58 of 112 (51.8%), respectively. Multivariate analysis indicated that the prognosis of patients with vertigo was correlated with vHIT gain of posterior canal, pathological saccade in horizontal canal, asymmetric ratio of horizontal canal gain, asymmetric ratio of posterior canal gain, Canal paresis (%) on caloric test and spontaneous nystagmus.

Conclusion

In the vHIT of patients with SSNHL with vertigo, the posterior canal is most easily affected. Reduced gain of posterior canal, pathological saccade of horizontal canal, and larger asymmetric gain of posterior canal and horizontal canal may be negative prognostic factors.
Optimal Chest Compression Point During Pediatric Resuscitation: Implications for Pediatric Resuscitation Practice by CT Scans*
Authors: Eimer Christine , Huhndorf Monika , Sattler Ole , Feth Maximilian , Jansen Olav , Gräsner Jan-Thorsten , Lorenzen Ulf , Albrecht Martin , Grünewald Matthias , Reifferscheid Florian , Seewald Stephan
Published: June 2024

OBJECTIVES:

Current European guidelines for pediatric cardiopulmonary resuscitation (CPR) recommend the lower half of the sternum as the chest compression point (CP). In this study, we have used thoracic CT scans to evaluate recommended and optimal CP in relation to cardiac anatomy and structure.

DESIGN:

Analysis of routinely acquired thoracic CT scans acquired from 2000 to 2020.

SETTING:

Single-center pediatric department in a German University Hospital.

PATIENTS:

Imaging data were obtained from 290 patients of 3–16 years old.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We measured and analyzed 14 thoracic metrics in each thoracic CT scan. In 44 of 290 (15.2%) scans, the recommended CP did not match the level of the cardiac ventricles. Anatomically, the optimal CP was one rib or one vertebral body lower than the recommended CP, that is, the optimal CP was more caudal to the level of the body of the sternum in 67 of 290 (23.1%) scans. The recommended compression depth appeared reasonable in children younger than 12 years old. At 12 years old or older, the maximum compression depth of 6 cm is less than or equal to one-third of the thoracic depth.

CONCLUSIONS:

In this study of thoracic CT scans in children 3–16 years old, we have found that optimal CP for CPR appears to be more caudal than the recommended CP. Therefore, it seems reasonable to prefer to use the lower part of the sternum for CPR chest compressions. At 12 years old or older, a compression depth similar to that used in adults—6 cm limit—may be chosen.
LINE-1 ORF1p is a Promising Biomarker in Cervical Intraepithelial Neoplasia Degree Assessment
Authors: Karkas Réka , Abdullah Khaldoon Sadiq Ahmed , Kaizer László , Ürmös Ádám , Raya May , Tiszlavicz Lilla , Pankotai Tibor , Nagy István , Mátés Lajos , Sükösd Farkas
Published: June 2024

Cervical intraepithelial neoplasia (CIN) represents a spectrum of preinvasive squamous lesions within the cervical epithelium, whose identification is a diagnostic challenge due to subtle histomorphological differences among its categories. This study explores ORF1p, a nucleic acid-binding protein derived from long interspersed nuclear element-1 (LINE-1), as a potential biomarker for enhancing CIN diagnosis. A comprehensive analysis of 143 cervical specimens, encompassing CIN I (n=20), CIN II (n=46), CIN III (n=14), invasive cancer (n=32), and nondysplastic cases (normal cervical epithelia (n=24) and atrophy (n=7) were conducted. ORF1p, Ki67, and p16 expressions were evaluated using immunohistochemistry. ORF1p immunopositivity was detected in the vast majority [110/112 (98.2%)] of dysplastic and neoplastic (CIN and invasive cancer) specimens, whereas 19/24 (79.2%) of normal cervical specimens lacked ORF1p expression. The observed pattern of ORF1p expression showed a progressively increasing extent and intensity with advancing CIN grades. CIN I exhibited mild ORF1p expression in the lower one or two-thirds of the cervical epithelium [14/16 (87.5%)], whereas CIN II demonstrated moderate to strong ORF1p expression spanning the lower two-thirds [29/46 (63.0%)]. Pronounced transepithelial ORF1p immunopositivity characterized CIN III cases [13/14 (92.8%)] and cervical cancer [30/32 (93.8%)]. These findings propose ORF1p as a valuable indicator even for detecting CIN I, effectively discerning them from normal cervical tissue (p < 0.0001). Our findings underscore the potential of ORF1p as an early diagnostic marker for cervical neoplasia.
Proximal Interphalangeal Joint Arthroplasty for Osteoarthritis: A Long-Term Follow-Up
Authors: Notermans Bo J. W. , Teunissen Joris S. , Hoogendam Lisa , de Boer Luitzen H. L. , Selles Ruud W. ,   Hand-Wrist Study Group, van der Heijden Brigitte E. P. A.
Published: June 2024

Background:

Previously published research describes short-term outcomes after proximal interphalangeal (PIP) joint arthroplasty; however, long-term outcomes are scarce. Therefore, the authors evaluated patient-reported outcomes and complications after a follow-up of at least 5 years following PIP joint arthroplasty.

Methods:

The authors used prospectively gathered data from patients undergoing PIP joint arthroplasty with silicone or surface replacement implants. Time points included preoperatively, 1 year postoperatively, and at least 5 years postoperatively. The authors were able to include 74 patients. Primarily, the authors focused on patient satisfaction with the treatment outcome, measured using a validated 5-point Likert scale. Secondary outcomes included the questions of whether patients would undergo the same surgery again, the assessment of factors associated with satisfaction or dissatisfaction, the Michigan Hand Outcomes Questionnaire score, and the number of reoperations.

Results:

The mean follow-up was 7 ± 1.2 years (range, 5 to 11 years). Patient satisfaction was excellent in 14 patients (19%), good in 17 patients (23%), reasonable in 18 patients (24%), moderate in 10 patients (14%), and poor in 15 patients (20%). Seventy-three percent of patients (n = 54) would undergo the same procedure again. The authors found no factors associated with satisfaction or dissatisfaction. All Michigan Hand Outcomes Questionnaire scores improved significantly in the first year after surgery and did not deteriorate afterward. Sixteen fingers (16%) required a reoperation, of which 3 (4%) needed a prosthesis replacement.

Conclusions:

Patient satisfaction with treatment outcomes 7 years after PIP implant surgery ranges from moderate to good for many patients, with a notable proportion expressing dissatisfaction. Patient-reported outcomes improve primarily within the first year and remain stable at 5 years or more.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.