bluuebunny/crossref_metadata_2025 huggingface dataset:
549 - Laboratory parameters in adolescent patients aged 12–17 with moderate-to-severe atopic dermatitis treated with tralokinumab up to week 52: results from the phase 3 ECZTRA 6 trial
Authors: Paller Amy , Cork Michael , Hong Chih-ho , Soong Weily , Schneider Shannon , Lo Hannah , Pedersen Line Rosendahl Meldgaard , Vacko Emilia , Wollenberg Andreas
Published: February 2024

Introduction/Background

Tralokinumab, a high-affinity, monoclonal antibody that targets IL-13, is approved in the EU and Canada for adolescents (aged ≥12 years) with inadequately controlled moderate-to-severe atopic dermatitis (AD), and it does not require laboratory monitoring. The phase 3 ECZTRA 6 (NCT03526861) clinical trial demonstrated efficacy and safety up to 52 weeks in that population.

Objectives

To further characterize the safety profile of tralokinumab by evaluating laboratory parameters of adolescents in the ECZTRA 6 trial.

Methods

ECZTRA 6 subjects received tralokinumab 150mg (n=98), 300mg (n=97) or placebo (n=94) every 2 weeks (Q2W) from week 0–16 after a loading dose at week 0 (twice the subsequent dose), and then randomized to maintenance [original tralokinumab dose either Q2W or every 4 weeks (Q4W) or placebo Q2W] or open-label (tralokinumab 300mg Q2W) until week 52. Laboratory parameters included hematology, serum biochemistry, and urinalysis throughout the trial (weeks 0, 8, 16, 28, and 52).

Results

Overall (n= 289 subjects), laboratory baseline parameters were similar across treatment groups. Mean and median changes of most hematology parameters showed minor fluctuations within the normal ranges through week 52, except for eosinophils. At baseline, elevated mean eosinophil counts (>0.5 109/L) were observed for 40.8% (tralokinumab 150mg), 48.5% (tralokinumab 300mg), and 43.6% (placebo) of subjects in each respective treatment group. Some tralokinumab-treated patients had small transient increases in eosinophils (maximum mean change from baseline 0.2×109/L) before week 16. Continued treatment with tralokinumab or placebo did not correspond with further increase in eosinophil levels over time, and no adverse events of eosinophilia were reported. Mean levels of most biochemistry parameters, including electrolytes, renal and liver function parameters, and lipid panel, were within normal range at baseline, and mean and median changes showed minor fluctuations within normal ranges in all treatment arms. Mean lactate dehydrogenase levels were around or above the upper limit of normal at baseline and decreased to within the normal ranges during the trial across all groups. Overall, no clinically meaningful differences were observed in hematology, biochemistry, or urinalysis parameters between active treatment groups or placebo.

Conclusions

Similar to findings in adult trials, no meaningful changes in laboratory parameters were observed in adolescents through week 52 with tralokinumab treatment. No routine laboratory monitoring is needed for adult or adolescent AD patients treated with tralokinumab.
Liver resection versus radiofrequency ablation or trans-arterial chemoembolization for early-stage (BCLC A) oligo-nodular hepatocellular carcinoma: meta-analysis
Authors: Romano Pierluigi , Busti Marco , Billato Ilaria , D’Amico Francesco , Marchegiani Giovanni , Pelizzaro Filippo , Vitale Alessandro , Cillo Umberto
Published: February 2024

Background

The 2022 Barcelona Clinic Liver Cancer (BCLC) algorithm does not recommend liver resection (LR) in BCLC A patients with oligo-nodular (two or three nodules ≤3 cm) hepatocellular carcinoma (HCC). This sharply contrasts with the therapeutic hierarchy concept, implying a precise treatment order exists within each BCLC stage. This study aimed to compare the outcomes of LR versus radiofrequency ablation (RFA) or trans-arterial chemoembolization (TACE) in BCLC A patients.

Methods

A meta-analysis adhering to PRISMA guidelines and the Cochrane Handbook was performed. All RCT, cohort and case–control studies that compared LR versus RFA or TACE in oligo-nodular BCLC A HCC published between January 2000 and October 2023 were comprehensively searched on PubMed, Embase, the Cochrane Library and China Biology Medicine databases. Primary outcomes were overall survival (OS) and disease-free survival (DFS) at 3 and 5 years. Risk ratio (RR) was computed as a measure of treatment effect (OS and DFS benefit) to calculate common and random effects estimates for meta-analyses with binary outcome data.

Results

2601 patients from 14 included studies were analysed (LR = 1227, RFA = 686, TACE = 688). There was a significant 3- and 5-year OS benefit of LR over TACE (RR = 0.55, 95% c.i. 0.44 to 0.69, P < 0.001 and RR 0.57, 95% c.i. 0.36 to 0.90, P = 0.030, respectively), while there was no significant 3- and 5-year OS benefit of LR over RFA (RR = 0.78, 95% c.i. 0.37 to 1.62, P = 0.452 and RR 0.74, 95% c.i. 0.50 to 1.09, P = 0.103, respectively). However, a significant 3- and 5-year DFS benefit of LR over RFA was found (RR = 0.70, 95% c.i. 0.54 to 0.93, P = 0.020 and RR 0.82, 95% c.i. 0.72 to 0.95, P = 0.015, respectively). A single study comparing LR and TACE regarding DFS showed a significant superiority of LR. The Newcastle–Ottawa Scale quality of studies was high in eight (57%) and moderate in six (43%).

Conclusions

In BCLC A oligo-nodular HCC patients, LR should be preferred to RFA or TACE (therapeutic hierarchy concept). Additional comparative cohort studies are urgently needed to increase the certainty of this evidence.
Bright silicon quantum dot synthesis and LED design: insights into size–ligand–property relationships from slow- and fast-band engineering
Authors: Saitow Ken-ichi
Published: February 2024

Multicolor, bright silicon quantum dots (SiQDs)—SiQDs with photoluminescence in a range of colors and quantum yields (PLQYs) of >90%—are promising heavy-metal-free light sources for full-color displays, lighting, and biomedical imaging. Colloidal SiQDs can be used to manufacture devices via printing and roll-to-roll processing. Furthermore, the in vivo use of biodegradable SiQDs and Si nanomaterials, for imaging cancer cells and as drug delivery systems, has been demonstrated. However, a large body of research demonstrates that the photoluminescence (PL) wavelength and PLQY of colloidal SiQDs are dependent not only on the SiQD particle size but also on the methods and/or procedures and chemical reagents used to synthesize them. This is because SiQDs are quite sensitive to both the intrinsic properties of Si and external factors. These intrinsic and external factors can be respectively linked to different PL mechanisms: the quantum confinement effect, which produces a slow-decaying “S”-band PL signal, and surface ligand effects, corresponding to fast-decaying “F”-band PL. This review focuses on mechanistic insights into the relationships linking the structures, ligands, and optical properties of SiQDs. Synthesis methods and the application performance of bright multicolor colloidal SiQDs, based on excellent state-of-the-art experimental and theoretical studies, are also reviewed.
The value added of machine learning to causal inference: evidence from revisited studies
Authors: Baiardi Anna , Naghi Andrea A
Published: February 2024

A new and rapidly growing econometric literature is making advances in the problem of using machine learning methods for causal inference questions. Yet, the empirical economics literature has not started to fully exploit the strengths of these modern methods. We revisit influential empirical studies with causal machine learning methods aiming to connect the econometric theory on these methods with empirical economics. We focus on the double machine learning, causal forest, and generic machine learning methods, in the context of both average and heterogeneous treatment effects. We illustrate the implementation of these methods in a variety of settings and highlight the relevance and value added relative to traditional methods used in the original studies.
Impact of coronary artery calcium on mortality and cardiovascular events in metabolic syndrome and diabetes among younger adults
Authors: Masrouri Soroush , Shapiro Michael D , Khalili Davood , Hadaegh Farzad
Published: February 2024

Aims

Whether coronary artery calcium (CAC) testing in younger individuals with metabolic syndrome (MetS) and diabetes mellitus (DM) helps predict cardiovascular disease (CVD) and death independent of traditional risk factors (RFs) remains less clear.

Methods and results

We pooled data obtained from 5174 individuals aged 38–55 years from the CARDIA (Coronary Artery Risk Development in Young Adults; n = 3047, year 20) and MESA (Multi-Ethnic Study of Atherosclerosis; n = 2127, Visit 1) studies who completed computed tomography of CAC. The mean age (SD) of participants (44.7% men) was 47.3 (4.2) years. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of CVD, coronary heart disease (CHD), and all-cause death. There were 1085 participants (21.0%) with prevalent CAC at baseline. A total of 461 (8.9%) had DM, 1025 (19.8%) had MetS without DM, and 3688 (71.3%) had neither condition. Over a median follow-up of 14.2 years, 256 (5.0%) participants died, and 304 (5.9%) CVD and 188 (3.6%) CHD events occurred. The CAC score was independently associated with incident CVD in those with DM (HR: 95% CI; 1.22: 1.08–1.38), MetS (1.18: 1.08–1.31), and neither condition (1.36: 1.26–1.46). The corresponding HRs for CAC ≥ 100 were 2.70 (1.25–5.83), 3.29 (1.87–5.79), and 6.30 (4.02–9.86), respectively. Similar associations for CHD and death were found. The impact of CAC ≥ 100 on CVD and CHD was lower in the presence of DM (P interaction < 0.05). The association of CAC with all outcomes in individuals with DM remained significant after adjusting with haemoglobin A1c levels.

Conclusion

Coronary artery calcium score is independently associated with cardiovascular events and death over nearly 15 years after screening at ages 38–55 years, with a less pronounced impact on CVD and CHD events in the presence of DM.
Automated Motive Scoring and International Crisis Behavior
Authors: Young Michael D
Published: February 2024

Although implicit motives are well established, coding for implicit motives has been a time-consuming and difficult manual process. This study (i) evaluates automated motive coding schemes for Need for Achievement, Need for Affiliation, and Need for Power, (ii) assesses the relationship between these three motives and crisis initiation, and (iii) assesses the explanatory power of other psychological variables for crisis behavior. The results establish the convergent validity of the Need for Achievement and Need for Power coding schemes with hand coding and support findings of a significant relationship between Need for Power and crisis behavior. A unit increase in Need for Power doubles the probability that a leader will initiate a crisis. Even stronger models were obtained by including other previously studied psychological variables. The scope of the dataset (154 leaders across a diverse set of 93 countries) lends weight to the findings and provides many opportunities for additional research.
A haplotype-resolved chromosome-level assembly and annotation of European hazelnut (C. avellana cv. Jefferson) provides insight into mechanisms of eastern filbert blight resistance
Authors: Talbot Samuel C , Vining Kelly J , Snelling Jacob W , Clevenger Josh , Mehlenbacher Shawn A
Published: February 2024

European hazelnut (Corylus avellana L.) is an important tree nut crop. Hazelnut production in North America is currently limited in scalability due to Anisogramma anomala, a fungal pathogen that causes Eastern Filbert Blight (EFB) disease in hazelnut. Successful deployment of EFB resistant cultivars has been limited to the state of Oregon, where the breeding program at Oregon State University (OSU) has released cultivars with a dominant allele at a single resistance locus identified by classical breeding, linkage mapping, and molecular markers. C. avellana cultivar “Jefferson” is resistant to the predominant EFB biotype in Oregon and has been selected by the OSU breeding program as a model for hazelnut genetic and genomic research. Here, we present a near complete, haplotype-resolved chromosome-level hazelnut genome assembly for “Jefferson”. This new assembly is a significant improvement over a previously published genome draft. Analysis of genomic regions linked to EFB resistance and self-incompatibility confirmed haplotype splitting and identified new gene candidates that are essential for downstream molecular marker development, thereby facilitating breeding efforts.
Online time series monitoring method of transformer based on seq2seq model
Authors: Lu Fei , Liu Fan
Published: February 2024

To monitor the operating conditions of transformers in real time and improve the monitoring accuracy of three-phase voltage, load current and power frequency of transformers, an online time series monitoring method of transformers based on the seq2seq model is proposed. The impedance, excitation current, secondary side voltage and excitation branch of the transformer are reduced to the primary side value, and the regulation coefficient of the transformer under no-load operation is calculated. By obtaining the short circuit impedance of the transformer, the short circuit impedance of the transformer is analysed. Using the coupling inductance model structure of single-phase double-winding and single-phase three-winding transformers, the parameter matrix of a single-phase double-winding transformer is established. According to the corresponding relationship between port electrical data and online monitoring information, the transformer coupling inductance model is constructed. The online time series monitoring process of the transformer is designed by using the seq2seq model, and the online time series monitoring of the transformer is realized. The experimental results show that when monitoring the three-phase voltage, load current and power frequency of the transformer, the monitoring errors are controlled below 0.5, 5 and 0.5%, respectively, which greatly improves the accuracy of online time series monitoring of the transformer.
Chronic obstructive pulmonary disease in East Africa: a systematic review and meta-analysis
Authors: Mebrahtom Guesh , Hailay Abrha , Mariye Teklewoini , Haile Teklehaimanot Gereziher , Girmay Goitom , Zereabruk Kidane , Aberhe Woldu , Tadesse Degena Bahrey
Published: February 2024

Chronic obstructive pulmonary disease (COPD) is a common lung disease that causes restricted airflow and breathing problems. Globally, COPD is the third leading cause of death and low- and middle-income countries account for the majority of these deaths. There is limited information on COPD's prevalence in East Africa. Thus the purpose of this systematic review and meta-analysis is to estimate the pooled prevalence of COPD in East Africa.A computerized systematic search using multiple databases was performed in search of relevant English articles from the inception of the databases to August 2023. All the authors independently extracted the data. R and RStudio software were used for statistical analysis. Forest plots and tables were used to represent the data. The statistical heterogeneity was evaluated using I2 statistics. There was heterogeneity between the included articles. Therefore, a meta-analysis of random effects models was used to estimate the overall pooled prevalence of COPD in East Africa. A funnel plot test was used to examine possible publication bias.The database search produced 512 papers. After checking for inclusion and exclusion criteria, 43 full-text observational studies with 68 553 total participants were found suitable for the review. The overall pooled prevalence of COPD in East Africa was 13.322%. The subgroup analysis found the COPD pooled prevalence in the different countries was 18.994%, 7%, 15.745%, 9.032%, 15.026% and 11.266% in Ethiopia, Uganda, Tanzania, Malawi, Sudan, and Kenya, respectively. Additionally, the subgroup analysis of COPD by study setting among community-based studies was 12.132% and 13.575% for hospital-based studies.According to the study's findings, approximately one of every seven individuals in East Africa has COPD, indicating a notably high prevalence of the disease. Thus governments and other stakeholders working on non-communicable disease control should place an emphasis on preventive measures to minimize the burden of COPD.
Evaluating the role of primary care pharmacy technicians in antimicrobial stewardship (AMS) and acne management using TARGET resources
Authors: Lakha Alishah , Fleming Naomi , Sonnex Kimberly , Thornley Tracey , Anderson Claire , Hand Kieran , Ashiru-Oredope Diane
Published: February 2024

Background

Inappropriate antibiotic prescribing is accelerating antimicrobial resistance (AMR) (Antibiotic resistant infections and associated deaths increase  https://www.gov.uk/government/news/antibiotic-resistant-infections-and-associated-deaths-increase). Pharmacy professionals (pharmacists and pharmacy technicians) promote good antibiotic prescribing practice. The traditional role of pharmacy technicians in supporting pharmacists and patients has expanded alongside the clinical expansion of pharmacist roles. (Boughen M, Fenn T. Practice, skill mix and education: the evolving role of pharmacy technicians in Great Britain. Pharmacy (Basel) 2020; 8(2): 50. doi:10.3390/pharmacy8020050) This paper focuses on the opinion of pharmacy technicians and their role in the review of acne management and the evaluation of the UKHSA TARGET acne ‘How to…’ review resources.

Aims and objectives

To explore the impact of the TARGET resources on the capability, opportunity and motivation of pharmacy technicians in general practice in managing patients with acne.

To evaluate the usefulness of the acne ‘How to…’ review resources.

Materials and methods

A primarily quantitative study using an electronic survey asking UK-based pharmacy technicians to rate their agreement on a five-point Likert scale with 21 predefined statements, themed on the COM-B model and usefulness of the TARGET resources for acne.

Discussion

The survey found that capability and opportunity in managing acne in the group familiar with TARGET resources was higher than the group not familiar with TARGET resources. Scores for motivation in both groups were high; pharmacy technicians have the motivation to undertake infection management roles, whether or not they are familiar with the TARGET toolkit.

The acne ‘How to…’ review resources were overall rated as useful in supporting the review of patients with acne.

Conclusion

The TARGET materials are effective resources that helps to upskill pharmacy technicians in the area of AMS, increasing capability and opportunity in the management of acne.
Antimicrobial consumption in an acute NHS Trust during the COVID-19 pandemic: intervention time series analysis
Authors: Khan Sidra , Bond Stuart E , Lee-Milner Jade , Conway Barbara R , Lattyak William J , Aldeyab Mamoon A
Published: February 2024

Objective

To determine the impact of the COVID-19 pandemic on antimicrobial consumption and trends of therapeutic drugs for COVID-19 treatments, including corticosteroids, remdesivir and monoclonal antibodies (tocilizumab) from April 2017 to September 2022 in a secondary care NHS Trust in England.

Methods

A retrospective intervention time series analysis was conducted for April 2017 to September 2022 at the Mid Yorkshire Teaching NHS Trust. Data were retrieved from the pharmacy dispensing system as defined daily doses (DDDs) monthly and reported per 1000 occupied bed days (OBDs). Antimicrobial consumption and COVID-19 treatment options were measured. DDDs were calculated according to the classification of antimicrobials for systemic use (J01) and for other drugs classification. Trends for antimicrobial consumption and other therapeutic drugs for treating COVID-19 were also determined in each wave in England.

Results

During the pandemic: total antibiotic consumption decreased from 826.4 to 728.2 DDDs per 1000 OBDs (P = 0.0067); piperacillin/tazobactam use increased (P < 0.0001) and ciprofloxacin use decreased (P < 0.0001); there were no changes in Access, Watch, Reserve antibiotic use, and the proportion of antifungal consumption was consistent throughout the study. The use of total antibiotics (P = 0.024), levofloxacin (P = 0.0007), piperacillin/tazobactam (P = 0.0015) and co-amoxiclav (P = 0.0198) increased during wave one. Consumption of COVID-19 treatment drugs was highest during wave two, with 624.3 DDDs per 1000 OBDs for dexamethasone (P = 0.4441), 6.8 DDDs per 1000 OBDs for remdesivir (P < 0.0001) and 35.01 DDDs per 1000 OBDs for tocilizumab (P = 0.2544).

Discussion

This study determined the consumption of antimicrobials trends before and during the pandemic. The individual wave antimicrobial consumption indicates maximum consumption in the first wave, advocating for antimicrobial stewardship and preparedness for future pandemics.
Maternal dietary intervention during lactation impacts the maternal faecal and human milk microbiota
Authors: Sindi Azhar S , Stinson Lisa F , Gridneva Zoya , Leghi Gabriela E , Netting Merryn J , Wlodek Mary E , Muhlhausler Beverly S , Rea Alethea , Trevenen Michelle L , Geddes Donna T , Payne Matthew S
Published: February 2024

Aims

To determine the effect of a two-week reduced fat and sugar and increased fibre maternal dietary intervention on the maternal faecal and human milk (HM) microbiomes.

Methods and results

Faecal swabs and HM samples were collected from mothers (n = 11) immediately pre-intervention, immediately post-intervention, and 4 and 8 weeks post-intervention, and were analysed using full-length 16S rRNA gene sequencing. Maternal macronutrient intake was assessed at baseline and during the intervention. Maternal fat and sugar intake during the intervention were significantly lower than pre-intervention (P = <0.001, 0.005, respectively). Significant changes in the bacterial composition of maternal faeces were detected after the dietary intervention, with decreases in the relative abundance of Bacteroides caccae (P = <0.001) and increases in the relative abundance of Faecalibacillus intestinalis (P = 0.006). In HM, the diet resulted in a significant increase in Cutibacterium acnes (P = 0.001) and a decrease in Haemophilus parainfluenzae (P = <0.001). The effect of the diet continued after the intervention, with faecal swabs and HM samples taken 4 and 8 weeks after the diet showing significant differences compared to baseline.

Conclusion

This pilot study demonstrates that short-term changes in maternal diet during lactation can alter the bacterial composition of the maternal faeces and HM.
Tumor-infiltrating γδ T cells as targets of immune checkpoint blockade in melanoma
Authors: Di Simone Marta , Corsale Anna Maria , Toia Francesca , Shekarkar Azgomi Mojtaba , Di Stefano Anna Barbara , Lo Presti Elena , Cordova Adriana , Montesano Luigi , Dieli Francesco , Meraviglia Serena
Published: February 2024

Melanoma is one of the most sensitive tumors to immune modulation, and the major challenge for melanoma patients’ survival is immune checkpoint inhibitor (ICI) therapy. γδ T lymphocytes play an antitumoral role in a broad variety of tumors including melanoma and they are optimal candidates for cellular immunotherapy. Thus, a comprehensive analysis of the correlation between γδ T cells and immune checkpoint receptors in the context of melanoma was conducted, with the aim of devising an innovative combined immunotherapeutic strategy. In this study, using the GEPIA2.0 database, a significant positive correlation was observed between the expression of γδ T cell–related genes (TRGC1, TRGC2, TCRD) and immune checkpoint genes (PDCD1, HAVCR2, LAG3), highlighting the potential role of γδ T cells in the immune response within melanoma. Moreover, flow cytometry analysis unveiled a significant augmentation in the population of γδ T cells within melanoma lesions, which exhibited the expression of immune checkpoint receptors including LAG3, TIM3, and PD1. Analysis of single-cell RNA sequencing data revealed a significant enrichment and functional reprogramming of γδ T cell clusters in response to ICIs. Interestingly, the effects of ICI therapy varied between Vδ1 and Vδ2 γδ T cell subsets, with distinct changes in gene expression patterns. Last, a correlation analysis between γδ T cell abundance, immune checkpoint gene expression, and clinical outcomes in melanoma patients showed that low expression of immune checkpoint genes, including LAG3, HAVCR2, and PDCD1, was associated with improved 1-year overall survival, emphasizing the significance of these genes in predicting patient outcomes, potentially outweighing the impact of γδ T cell abundance. This study offers critical insights into the dynamic interaction between γδ T cells, immune checkpoint receptors, and melanoma, providing valuable perspectives for potential therapeutic avenues and predictive markers in this intricate interplay.
Landscape and farm environmental structure determinants of small mammal assemblages in agroecosystems of central Argentina
Authors: Alonso Rodrigo Javier , Lovera Rosario , Fernández María Soledad , Cavia Regino
Published: February 2024

Natural processes and patterns are altered by human activity at different spatial and temporal scales, affecting species assemblages and population traits, modifying mechanisms or regulating dynamics at different scales. However, little is known about the influence of landscape structure on small mammal assemblages and populations on farms. Thus, in this work, we aimed to study the effect of landscape and environmental characteristics at the farm scale on the assemblage and populations of native and introduced small mammals in pig and dairy farms located in Buenos Aires province, Argentina. Our results showed that farms in contexts of higher environmental diversity at the landscape scale have higher species richness. Our results also showed that variations in assemblage composition were associated with the quantity of water body surfaces, cattle food, small mammal refugia, and impervious surfaces at the farm scale—and with woodland, grassland, and natural vegetation cover at the landscape scale. The abundance of commensal murids was higher on farms near towns, with higher vegetation cover at the farm scale and/or in landscape contexts with fewer crops. The abundance of Akodon azarae was higher on farms with a lower amount of cattle food at the farm scale and crop patches in the landscape. The abundance of Didelphis albiventris was higher during spring on farms with a low proportion of bare ground, while that of Lutreolina crassicaudata was higher on farms with high vegetation cover and a lower number of water body surfaces. These results show the relevance of multiscale determinants in the development of ecologically based management strategies to control pest small mammals.
Altered 5-HT2A/C receptor binding in the medulla oblongata in the sudden infant death syndrome (SIDS): Part II. Age-associated alterations in serotonin receptor binding profiles within medullary nuclei supporting cardiorespiratory homeostasis
Authors: Cummings Kevin J , Leiter James C , Trachtenberg Felicia L , Okaty Benjamin W , Darnall Robert A , Haas Elisabeth A , Harper Ronald M , Nattie Eugene E , Krous Henry F , Mena Othon J , Richerson George B , Dymecki Susan M , Kinney Hannah C , Haynes Robin L
Published: February 2024

The failure of chemoreflexes, arousal, and/or autoresuscitation to asphyxia may underlie some sudden infant death syndrome (SIDS) cases. In Part I, we showed that some SIDS infants had altered 5-hydroxytryptamine (5-HT)2A/C receptor binding in medullary nuclei supporting chemoreflexes, arousal, and autoresuscitation. Here, using the same dataset, we tested the hypotheses that the prevalence of low 5-HT1A and/or 5-HT2A/C receptor binding (defined as levels below the 95% confidence interval of controls—a new approach), and the percentages of nuclei affected are greater in SIDS versus controls, and that the distribution of low binding varied with age of death. The prevalence and percentage of nuclei with low 5-HT1A and 5-HT2A/C binding in SIDS were twice that of controls. The percentage of nuclei with low 5-HT2A/C binding was greater in older SIDS infants. In >80% of older SIDS infants, low 5-HT2A/C binding characterized the hypoglossal nucleus, vagal dorsal nucleus, nucleus of solitary tract, and nuclei of the olivocerebellar subnetwork (important for blood pressure regulation). Together, our findings from SIDS infants and from animal models of serotonergic dysfunction suggest that some SIDS cases represent a serotonopathy. We present new hypotheses, yet to be tested, about how defects within serotonergic subnetworks may lead to SIDS.
The Japanese nationwide cohort data of proton beam therapy for liver oligometastasis in breast cancer patients
Authors: Yamaguchi Hisashi , Fukumitsu Nobuyoshi , Numajiri Haruko , Ogino Hiroyuki , Okimoto Tomoaki , Ogino Takashi , Suzuki Motohisa , Murayama Shigeyuki
Published: February 2024

A nationwide multicenter cohort study on particle therapy was launched by the Japanese Society for Radiation Oncology in Japan in May 2016. We analyzed the outcome of proton beam therapy (PBT) for liver oligometastasis in breast cancers. Cases in which PBT was performed at all Japanese proton therapy facilities between May 2016 and February 2019 were enrolled. The patients were selected based on the following criteria: the primary cancer was controlled, liver recurrence without extrahepatic tumors and no more than three liver lesions. Fourteen females, with a median age of 57 years (range, 44–73) and 22 lesions, were included. The median lesion size, fraction (fr) size and biological effective dose were 44 (20–130) mm, 6.6 (2–8) gray (Gy) (relative biological effectiveness)/fr and 109.6 (52.7–115.2) Gy, respectively. The median follow-up period was 22.8 (4–54) months. The 1-, 2- and 3-year local control (LC) rates of liver metastasis from breast cancer were 100% for all. The 1-, 2- and 3-year overall survival rates were 85.7, 62.5 and 62.5%, respectively. The 1-, 2- and 3-year progression-free survival (PFS) rates were 50.0%, 33.3%, and 16.7%, respectively. The median PFS time was 16 months. Only one patient did not complete PBT due to current disease progression. One patient had Grade 3 radiation-induced dermatitis. None of the patients experienced radiation-induced liver failure during the acute or late phase. Owing to the low incidence of adverse events and the high LC rate, PBT appears to be a feasible option for liver oligometastasis in breast cancers.
Dural metastasis of prostate carcinoma mimicking intracranial hematoma: a case report and literature review
Authors: Kokot Klaudia , Dzierżanowski Jarosław , Krakowiak Michał , Fercho Justyna , Yuser Rami , Kosel Laura , Nowiński Eryk , Nacewicz Jacek , Modliborska Dorota , Szmuda Tomasz , Zieliński Piotr
Published: February 2024

Dural metastases of prostate adenocarcinoma are an extremely rare complication and may mimic intracranial hematoma. Preoperatively diagnosis may be difficult due to similarities in symptoms and radiological appearance. We present a 65-year-old man admitted to the ED with a history of headache, nausea, vomiting, vertigo, diplopia, as well as numbness of his left lower extremity. Past medical history confirmed metastatic prostate cancer disease. After computed tomography and contrast computed tomography, the consulting radiologist diagnosed a chronic subdural hematoma. After burr hole trephination and dural opening, tumorous mass was detected. Histopathologic samples were taken. Histopathological examination was consistent with metastatic adenocarcinoma of the prostate. Although rare, dural metastases need to be included in oncological patients presenting in the ED with symptoms and radiological imaging suggesting hematoma. Both neurooncological and neurosurgical consultations are essential in order to apply the best treatment strategy.
Mid-term outcomes of hypogastric artery embolization in endovascular aneurysm repair: a case series
Authors: Kanemura Takeyuki , Nakahara Yoshinori , Tateishi Retsu , Haba Fumiya , Ono Shunya
Published: February 2024

Hypogastric artery embolization is performed during endovascular aneurysm repair (EVAR) involving the common iliac artery. Within this case series, we have observed elevated rates of sac expansion subsequent to this intervention. April 2009 to March 2021, 22 patients underwent EVAR with hypogastric artery embolization. We evaluated the mid-term outcomes for these patients. The mean follow-up period was 57 months. We achieved a 100% technical success rate without open conversion and no hospital deaths. The rates of freedom from aneurysm expansion at 1, 3, and 5 years were 90.5%, 59.1%, and 37.5%, respectively. The percentage of sac expansion exceeding 5 mm was 54.5% (12/22). Combined endovascular aortic aneurysm repair and embolization of the hypogastric artery might be associated with a high rate of remote sac expansion. Larger trials are needed to verify risks and benefits.
Giant dilatation of pancreatic duct associated with congenital anomaly of the pancreatic ductal system and small neuroendocrine tumor
Authors: Markov Pavel , Karmazanovsky Grigory , Lysenko Andrey , Arutyunov Ovanes , Kalinin Dmitry , Burmistrov Alexander
Published: February 2024

Dilatation of the main pancreatic duct (MPD) ˃50 mm is a rare phenomenon. We present the case of successful surgical treatment a 63-year-old female patient who presented epigastric pain and weight loss of 10 kg in 6 months. Based on preoperative examination, the dilatation of MPD was 75 mm. The preliminary diagnosis was main duct intraductal papillary mucinous neoplasm. Extended pylorus-preserving pancreatoduodenectomy with resection of the body of the pancreas was performed. According to the results of pathological and immunohistochemical studies, performed by independent experts, the final diagnosis of congenital anomaly of the ductal system and neuroendocrine tumor of the accessory pancreatic duct was made.
Dorsal lunate dislocation and en bloc proximal row carpectomy: a case report
Authors: Campano Dominic , Rush Kaitlin , Gottlich Caleb , Jain Neil , Bourland Bryan , Mckee Desirae
Published: February 2024

An unhelmeted 59-year-old male involved in a motorcycle accident presented with a right dorsal lunate dislocation in the context of a polytrauma evaluation. Soft-tissue attachments were minimal across the carpus, which allowed for an en bloc proximal row carpectomy. Two-year follow-up yielded a satisfactory outcome given the high energy injury mechanism. Proximal row carpectomy is a useful tool which preserves wrist range of motion in the acute trauma setting and is durable, as demonstrated by our patient’s postoperative mobilization using a wheelchair.
The American Haskalah: Sanctifying Education in Mary Antin’s The Promised Land, Abraham Cahan’s The Rise of David Levinsky, and Anzia Yezierska’s Bread Givers
Authors: Reznick Ohad
Published: February 2024

Much has been written about European Jews’ attitudes toward secular studies. The Jewish Enlightenment, which began in Europe in the early eighteenth century, caused some Jews to broaden their knowledge by learning subjects such as geography and science. However, most Eastern European Jews remained loyal to the rabbinical authority. When many immigrated to the United States during the Progressive Era, they had to choose between maintaining the old approach toward secular education and learning secular subjects. Analyzing three Jewish immigrant texts, Mary Antin’s The Promised Land (1912), Abraham Levinsky’s The Rise of David Levinsky (1917), and Anzia Yezierska’s Bread Givers (1925), this essay argues that these books present Eastern European Jewish immigrants as treating secular education similar to the European maskilim. Exploring Biblical allusions and imagery used to portray Torah learning, this paper determines that these texts sanctify nonreligious studies. Following a centuries-old heritage of learning, they glorify the knowledge obtained in American institutions. Although the protagonists feel they are betraying their tradition, they participate in establishing a Jewish American culture based on the value of studying. While these texts often praise American education, they portray a clash between American and traditional Jewish education, suggesting that disavowing one’s traditional education is challenging.
Incidence and Risk Factors for Bone Stress Injuries in United States Air Force Special Warfare Trainees
Authors: Johnson Andrew S , Brismée Jean-Michel , Hooper Troy L , Hintz Courtney N , Hando Benjamin R
Published: February 2024

Objectives

To determine (1) the incidence rate of lower extremity (LE) bone stress injuries (BSIs) in United States Air Force Special Warfare (AFSPECWAR) trainees during the first 120 days of training, and (2) factors associated with sustaining a LE BSI.

Design

Retrospective cohort study.

Methods

AFSPECWAR Airmen (n = 2,290, mean age = 23.7 ± 3.6 years) entering an intensive 8-week preparatory course “SW-Prep” between October 2017 and May 2021. We compared anthropometric measurements, previous musculoskeletal injury (MSKI), fitness measures, and prior high-impact sports participation in those that did and did not suffer a BSI during the 120-day observation period using independent t-tests and chi-square tests. A multivariable binary logistic regression was used to determine factors associated with suffering a BSI.

Results

A total of 124 AFSPECWAR trainees suffered a BSI during the surveillance period, yielding an incidence proportion of 5.41% and an incidence rate of 1.4 BSIs per 100 person-months. The multivariate logistic regression revealed that lower 2-minute sit-up scores, no prior history of participation in a high-impact high-school sport, and a history of prior LE MSKI were associated with suffering a BSI. A receiver operator characteristic curve analysis yielded an area under the curve (AUC) of 0.727.

Conclusion

BSI incidence proportion for our sample was similar to those seen in other military settings. Military trainees without a history of high-impact sports participation who achieve lower scores on sit-ups tests and have a history of LE MSKI have a higher risk for developing a LE BSI during the first 120 days of AFSPECWAR training.
The evolution of collision debris near the ν6 secular resonance and its role in the origin of terrestrial water
Authors: Süli Á , Forgács-Dajka E
Published: February 2024

This work presents novel findings that broaden our understanding of the amount of water that can be transported to the Earth. The key innovation lies in the combined usage of smoothed particle hydrodynamics (SPH) and N-body codes to assess the role of collision fragments in water delivery. We also present a method for generating initial conditions that enables the projectile to impact at the designated location on the target’s surface with the specified velocity. The primary objective of this study is to simulate giant collisions between two Ceres-sized bodies by SPH near the ν6 secular resonance and follow the evolution of the ejected debris by numerical N-body code. With our method 6 different initial conditions for the collision were determined, and the corresponding impacts were simulated by SPH. Examining the orbital evolution of the debris ejected after collisions, we measured the amount of water delivered to the Earth, which is broadly 0.001 ocean equivalents of water, except in one case where one large body transported 7 per cent oceans of water to the planet. Based on this and taking into account the frequency of collisions, the amount of delivered water varies between 1.2 and 8.3 ocean’s worth of water, depending on the primordial disc mass. According to our results, the prevailing external pollution model effectively accounts for the assumed water content on the Earth, whether it’s estimated at 1 or 10 ocean’s worth of water.
Collimated synchrotron threads in wide-angle-tail radio galaxies: cosmic thunderbolts?
Authors: Gopal-Krishna  , Biermann Peter L
Published: February 2024

The WAT (wide-angle-tail) radio galaxies ESO 137-006 and 3C338 show radio filaments including some extending between the two radio tails. If, in analogy to the Parker solar wind model, jets carry a powerful relativistic electric current, the continuity equation shows that slow return current responding to a temporal variation in jet power would inevitably lead to a localized short-lived charging-up, i.e. a temporary patch of electric field. Progenitors of the observed radio filaments are the relic jets left by repeated episodes of nuclear activity and pushed sideways by the ram pressure, though remaining connected to the broad radio lobes. The Debye shielding distance, for energetic particles with a p−2-distribution of momentum p, allows a very large Debye scale at the highest energies, approaching the radio galaxy scale, with a huge total energy content. Here, we propose that discharges dissipating the transient patches of electric fields through the filaments illuminate them. Our proposal is based on gradient drift currents within the bipolar jets, allowing for drift speeds approaching the speed of light. We sketch a scenario how a discharge current sometimes gets manifested as a radio filament connecting opposite lobes/tails of a WAT radio galaxy.
Extending MeCP2 interactome: canonical nucleosomal histones interact with MeCP2
Authors: Ortega-Alarcon David , Claveria-Gimeno Rafael , Vega Sonia , Kalani Ladan , Jorge-Torres Olga C , Esteller Manel , Ausio Juan , Abian Olga , Velazquez-Campoy Adrian
Published: February 2024

MeCP2 is a general regulator of transcription involved in the repression/activation of genes depending on the local epigenetic context. It acts as a chromatin regulator and binds with exquisite specificity to gene promoters. The set of epigenetic marks recognized by MeCP2 has been already established (mainly, cytosine modifications in CpG and CpA), as well as many of the constituents of its interactome. We unveil a new set of interactions for MeCP2 with the four canonical nucleosomal histones. MeCP2 interacts with high affinity with H2A, H2B, H3 and H4. In addition, Rett syndrome associated mutations in MeCP2 and histone epigenetic marks modulate these interactions. Given the abundance and the structural/functional relevance of histones and their involvement in epigenetic regulation, this new set of interactions and its modulating elements provide a new addition to the ‘alphabet’ for this epigenetic reader.
Selection-free precise gene repair using high-capacity adenovector delivery of advanced prime editing systems rescues dystrophin synthesis in DMD muscle cells
Authors: Wang Qian , Capelletti Sabrina , Liu Jin , Janssen Josephine M , Gonçalves Manuel A F V
Published: February 2024

Prime editors have high potential for disease modelling and regenerative medicine efforts including those directed at the muscle-wasting disorder Duchenne muscular dystrophy (DMD). However, the large size and multicomponent nature of prime editing systems pose substantial production and delivery issues. Here, we report that packaging optimized full-length prime editing constructs in adenovector particles (AdVPs) permits installing precise DMD edits in human myogenic cells, namely, myoblasts and mesenchymal stem cells (up to 80% and 64%, respectively). AdVP transductions identified optimized prime-editing reagents capable of correcting DMD reading frames of ∼14% of patient genotypes and restoring dystrophin synthesis and dystrophin-β-dystroglycan linkages in unselected DMD muscle cell populations. AdVPs were equally suitable for correcting DMD iPSC-derived cardiomyocytes and delivering dual prime editors tailored for DMD repair through targeted exon 51 deletion. Moreover, by exploiting the cell cycle-independent AdVP transduction process, we report that 2- and 3-component prime-editing modalities are both most active in cycling than in post-mitotic cells. Finally, we establish that combining AdVP transduction with seamless prime editing allows for stacking chromosomal edits through successive delivery rounds. In conclusion, AdVPs permit versatile investigation of advanced prime editing systems independently of their size and component numbers, which should facilitate their screening and application.
Pleasure, Pain, and Pluralism about Well-Being
Authors: Lin Eden
Published: February 2024

Pluralistic theories of well-being might appear unable to accommodate just how important pleasure and pain are to well-being. Intuitively, there is a finite limit to how well your life can go for you if it goes badly enough hedonically (e.g. because you never feel any pleasure and you spend two years in unrelenting agony). But if there is some basic good distinct from pleasure, as any pluralistic theory must claim, then it seems that you could be made arbitrarily well off by being given enough of that good even if your life is hedonically terrible. My aim is to defend pluralistic theories against this objection. After replying to the simplest version of it, I will answer a more sophisticated version of it that has recently been leveled by Theron Pummer.
The impact of the COVID-19 pandemic on childhood obesity rates, by Health Board area, in Wales, UK
Authors: Beynon Claire , Davies Llion
Published: February 2024

Background

The aim of this study was to examine the possible impact of the coronavirus pandemic on rates of children living with obesity and severe obesity, by Health Board area in Wales.

Methods

The pre-pandemic data consisted of all children included in the Wales Childhood Measurement Programme (2014/15–2018/19). The 2021/22 Child Measurement Programme data were used as the post-pandemic data set. Body mass index for obesity and severe obesity were calculated as 95th and 99.6th centiles, respectively.

Results

Of the 163 277 children measured pre-pandemic (2014/15 to 2018/19), the overall prevalence of children with obesity and severe obesity were 12.1 and 3.2%, respectively. In the post-pandemic year (2021/22), obesity increased to 15.5% and severe obesity increased to 4.8%, with clear deprivation differentials (noting one of the seven Health Boards was unable to submit data post-pandemic). Two Health Boards had significantly higher rates of obesity post-pandemic compared to pre-pandemic. Increased levels of severe obesity were observed in all Health Boards with available data.

Conclusion

The post-pandemic rise in obesity and severe obesity in young children living in Wales demonstrates a need for more work on the prevention of obesity and severe obesity, targeting the early years and areas of socio-economic disadvantage.