bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Congenital Syphilis Still a Problem?—A 20-Year Retrospective Study from a Northern Portuguese Level II Hospital
Authors: Figueiredo Ana Sofia , Quintela Carolina , Cascais Mafalda , Calviño Juan , Sousa Marisa , Pereira António , Soares Isabel
Published: December 2023

Objective The incidence of syphilis and congenital syphilis has increased in recent years according to European and United States of America official data: indeed, 2019 was the second consecutive year when the number of reported cases has increased. Syphilis is a venereal disease caused by a spirochete, Treponema pallidum. Congenital syphilis is a consequence of maternal T. palidum transmission to a fetus at any stage of maternal disease, via a transplacental pathway or during labor.

Methods To investigate the incidence, characteristics, and temporal evolution of neonates with suspected congenital syphilis (proven, possible, or less likely and unlikely) or born from mothers with treated and untreated latent syphilis, we designed a retrospective and descriptive study of hospitalized neonates between 2001 and 2020, in a level II hospital located in the northern Portuguese countryside.

Results We report a total of 22 neonates, 50% female. Pregnancy was unsupervised or had inadequate surveillance in 36% of cases (n = 8), in 32% (n = 7) syphilis was not treated, and in 14% (n = 3) it was inadequately treated. All neonates studied with suspected congenital syphilis were asymptomatic and all were treated with penicillin for a mean duration of 11 days. Of the 22 neonates with suspected congenital syphilis, 20 had possible congenital infection. Social vulnerability was also an important factor present in our study group.

Conclusion Despite being an ancient disease, congenital syphilis is still a concern mostly due to the lack of adequate pregnancy surveillance and maternal/partner diagnosis and treatment.
Anterior Spinal Artery Syndrome in a 14-Year-Old Boy
Authors: Watermeyer Fabian , Stampfli Martha L. , Hahn Markus , Markart Stefan , Gessler Peter
Published: December 2023

Acute flaccid paralysis caused by anterior spinal artery syndrome (ASAS) is rare in children. It typically manifests as bilateral loss of motor function, pain, and temperature sensation below the level of occlusion, with relatively little impairment in proprioception and vibration sense. We present such a case in a 14-year-old child who presented with a sudden onset of neck pain followed by the typical symptoms of ASAS with impaired breathing due to the height of the lesion, which was found in the magnetic resonance imaging examination at the level of C1–5. An initially suspected thrombogenic cause proved inapplicable. Ultimately, despite extensive diagnosis, as in most cases of ASAS in children, the cause remains unclear.
Gaining Insights into Inherited Bleeding Disorders of Complex Etiology in Pediatric Patients: Whole-Exome Sequencing as First-Line Investigation Tool
Authors: Bandini Perla , Borràs Nina , Berrueco Ruben , Gassiot Susanna , Martin-Fernandez Laura , Sarrate Edurne , Comes Natàlia , Ramírez Lorena , Hobeich Carlos , Vidal Francisco , Corrales Irene
Published: December 2023

Introduction Investigation of the molecular basis of inherited bleeding disorders (IBD) is mostly performed with gene panel sequencing. However, the continuous discovery of new related genes underlies the limitation of this approach. This study aimed to identify genetic variants responsible for IBD in pediatric patients using whole-exome sequencing (WES), and to provide a detailed description and reclassification of candidate variants.

Material and Methods WES was performed for 18 pediatric patients, and variants were filtered using a first-line list of 290 genes. Variant prioritization was discussed in a multidisciplinary team based on genotype-phenotype correlation, and segregation studies were performed with available family members.

Results The study identified 22 candidate variants in 17 out of 18 patients (94%). Eleven patients had complete genotype-phenotype correlation, resulting in a diagnostic yield of 61%, 5 (28%) were classified as partially solved, and 2 (11%) remained unsolved. Variants were identified in platelet (ACTN1, ANKRD26, CYCS, GATA1, GFI1B, ITGA2, NBEAL2, RUNX1, SRC, TUBB1), bleeding (APOLD1), and coagulation (F7, F8, F11, VWF) genes. Notably, 9 out of 22 (41%) variants were previously unreported. Variant pathogenicity was assessed according to the American College of Medical Genetics and Genomics guidelines and reclassification of three variants based on family segregation evidence, resulting in the identification of 10 pathogenic or likely pathogenic variants, 6 variants of uncertain significance, and 6 benign or likely benign variants.

Conclusion This study demonstrated the high potential of WES in identifying rare molecular defects causing IBD in pediatric patients, improving their management, prognosis, and treatment, particularly for patients at risk of malignancy and/or bleeding due to invasive procedures.
Laparoscopic ventral hernia repair: early follow-up of a randomized controlled study of primary fascial closure before mesh placement
Authors: Silfvenius Annie U K , Lindmark Mikael E , Tall Jael V , Österberg Johanna K , Strigård Karin K , Thorell Anders , Gunnarsson Ulf S
Published: December 2023

Background

Suturing of the hernia aperture in laparoscopic ventral hernia repair has increased during the past decade. The primary aim of this is to restore the anatomy of the abdominal wall. Closure of the aperture, however, may cause additional tension in the abdominal wall which could increase postoperative pain. The aim of this study was to investigate whether suturing of the hernia aperture affects postoperative pain and hernia-site complications, including seroma, infection, pseudohernia, and mesh migration, 3 months after repair.

Methods

Some 192 patients with a midline hernia between 2 and 8 cm in transverse diameter were included in a randomized controlled double-blinded multicentre study. Patients were randomized to mesh repair with (intervention) or without (control) suturing of the hernia aperture before mesh placement. Patients completed the Ventral Hernia Pain Questionnaire before and 3 months after surgery. Abdominal wall pain and hernia-site complications were assessed 3 months after surgery.

Results

Ninety-seven patients were randomized to the intervention group and 95 to the control group. Among all patients, median age and BMI was 56 years and 31 kg/m2 respectively. Overall pain experienced decreased by 3 months after operation (P < 0.001). There was no difference between groups regarding hernia-site complications or pain experienced during the past week (13 versus 23 patients; P = 0.111). Seroma and pseudohernia occurred in 13 and 11 patients in the intervention and control groups respectively (P = 0.975 and P = 0.977).

Conclusion

Restoration of the abdominal wall anatomy by suturing the hernia aperture before mesh placement does not increase the risk of hernia-site complication or pain 3 months after surgery. This implies that fascial suturing of the aperture can be justified if there are potential long-term benefits such as lower recurrence and/or complication rates. Registration number: ISRCTN51495042 (http://www.controlled-trials.com).
Benefit allocation of electricity–gas–heat–hydrogen integrated energy system based on Shapley value
Authors: Liu Yujiao , Li Yan , Rong Yiping , Li Guoliang , Wang Ruiqi , Zhou Haini
Published: December 2023

The integrated energy system is an important development direction for achieving energy transformation in the context of the low-carbon development era, and an integrated energy system that uses renewable energy can reduce carbon emissions and improve energy utilization efficiency. The electric power network and the natural gas network are important transmission carriers in the energy field, so the coupling relationship between them has been of wide concern. This paper establishes an integrated energy system considering electricity, gas, heat and hydrogen loads; takes each subject in the integrated energy system as the research object; analyses the economic returns of each subject under different operation modes; applies the Shapley value method for benefit allocation; and quantifies the contribution value of the subject to the alliance through different influencing factors to revise the benefit allocation value. Compared with the independent mode, the overall benefits of the integrated energy system increase in the cooperative mode and the benefits of all subjects increase. Due to the different characteristics of different subjects in terms of environmental benefits, collaborative innovation and risk sharing, the benefit allocation is reduced for new-energy subjects and increased for power-to-gas subjects and combined heat and power generation units after revising the benefit allocation, to improve the matching degree between the contribution level and the benefit allocation under the premise of increased profit for each subject. The cooperative mode effectively enhances the economic benefits of the system as a whole and individually, and provides a useful reference for the allocation of benefits of integrated energy systems. The analysis shows that the revised benefit distribution under the cooperative model increases by 3.86%, 4.08% and 3.13% for power-to-gas subjects, combined heat and power generation units, and new-energy units, respectively, compared with the independent function model.
The role of time and space in the identification of left behind regions: a case study of Denmark
Authors: Jessen Sigrid
Published: December 2023

This paper provides an overview of the state of identification of left behind regions and proposes a new methodology for identifying them. Despite increased interest in rising regional inequality, the identification of left behind regions differs greatly, complicating policymaking aimed at addressing these regional challenges. Based on the substantial literature that has emerged in recent years on left behind regions, the paper argues for the importance of both time and space as key elements when identifying left behind regions. This paper applies the proposed identification method to Denmark; it uses longitudinal data from 1980 to 2018 and includes the current wave of interregional inequality and typically adopted variables for identifying left behind regions across the literature.
High-Quality Genome Assemblies Reveal Evolutionary Dynamics of Repetitive DNA and Structural Rearrangements in the Drosophila virilis Subgroup
Authors: Flynn Jullien M , Ahmed-Braimah Yasir H , Long Manyuan , Wing Rod A , Clark Andrew G
Published: December 2023

High-quality genome assemblies across a range of nontraditional model organisms can accelerate the discovery of novel aspects of genome evolution. The Drosophila virilis group has several attributes that distinguish it from more highly studied species in the Drosophila genus, such as an unusual abundance of repetitive elements and extensive karyotype evolution, in addition to being an attractive model for speciation genetics. Here, we used long-read sequencing to assemble five genomes of three virilis group species and characterized sequence and structural divergence and repetitive DNA evolution. We find that our contiguous genome assemblies allow characterization of chromosomal arrangements with ease and can facilitate analysis of inversion breakpoints. We also leverage a small panel of resequenced strains to explore the genomic pattern of divergence and polymorphism in this species and show that known demographic histories largely predicts the extent of genome-wide segregating polymorphism. We further find that a neo-X chromosome in Drosophila americana displays X-like levels of nucleotide diversity. We also found that unusual repetitive elements were responsible for much of the divergence in genome composition among species. Helitron-derived tandem repeats tripled in abundance on the Y chromosome in D. americana compared to Drosophila novamexicana, accounting for most of the difference in repeat content between these sister species. Repeats with characteristics of both transposable elements and satellite DNAs expanded by 3-fold, mostly in euchromatin, in both D. americana and D. novamexicana compared to D. virilis. Our results represent a major advance in our understanding of genome biology in this emerging model clade.
The Epidemiology of Inflammatory Bowel Disease in Oceania: A Systematic Review and Meta-Analysis of Incidence and Prevalence
Authors: Forbes Angela J , Frampton Chris M A , Day Andrew S , Kaplan Gilaad G , Gearry Richard B
Published: December 2023

Background

Past studies have shown high rates of inflammatory bowel disease (IBD) in Australia and New Zealand (NZ). We aimed to describe the epidemiology of IBD in Australia, NZ, and the surrounding region (collectively termed Oceania) by conducting a systematic review and meta-analysis.

Methods

Electronic databases were searched from inception to April 2023 for studies reporting incidence or prevalence rates of IBD, Crohn’s disease (CD), or ulcerative colitis (UC) in Oceania. All study designs were included. A meta-analysis calculated pooled estimates of incidence and prevalence, and a sensitivity analysis compared the pooled population-based studies with the non–population-based studies and the Australian and NZ studies separately.

Results

Nineteen incidence and 11 prevalence studies were included; 2 studies were from the Pacific Islands, with the rest coming from Australia and NZ. Pooled estimates showed high incidence rates of 19.8 (95% confidence interval [CI], 15.8-23.7) for IBD, 8.3 (95% CI, 6.9-9.8) for CD, and 7.4 (95% CI, 5.7-9.1) for CD per 100 000 person-years. CD was more common than UC in most studies. The pooled estimates for the prevalence studies were 303.3 (95% CI, 128.1-478.4) for IBD, 149.8 (95% CI, 71.0-228.5) for CD, and 142.2 (95% CI, 63.1-221.4) for UC per 100 000 persons. Studies using population-based data collection methods showed higher pooled rates for both incidence and prevalence.

Conclusions

The incidence and prevalence of IBD in Oceania is high. The studies were heterogeneous and there were several geographic areas with no information, highlighting the need for more epidemiological studies of IBD.
The Clinical Interpretation of Noninferiority Trials
Authors: Roshanov Pavel S , Khanna Reena
Published: December 2023

Noninferiority trials are designed to demonstrate that a new treatment is not unacceptably worse than a standard treatment, considering an allowable difference termed the noninferiority margin. We highlight that selection of noninferiority margins at the time of study design can be biased toward wider margins that favor noninferiority claims. We discuss a clinically oriented approach to interpretation of results with a focus on confidence intervals and recommend that readers base their judgments regarding noninferiority on margins reflecting patient values and preferences rather than those set by investigators. We provide examples from trials in inflammatory bowel diseases.
Vibrio species: development of EUCAST susceptibility testing methods and MIC and zone diameter distributions on which to determine clinical breakpoints
Authors: Karatuna Onur , Matuschek Erika , Åhman Jenny , Caidi Hayat , Kahlmeter Gunnar
Published: December 2023

Objectives

Most human infections caused by Vibrio spp. do not warrant antimicrobial treatment but in severe cases, targeted antimicrobial treatment can be lifesaving. For Vibrio spp., standardized antimicrobial susceptibility testing (AST) guidelines with EUCAST methodology are lacking. In this study, we aimed to produce data suitable for EUCAST to establish clinical MIC breakpoints and zone diameter correlates for Vibrio spp.

Methods

An intercontinental collection (N = 524) comprising five important Vibrio spp. (V. alginolyticus, V. cholerae, V. fluvialis, V. parahaemolyticus and V. vulnificus) was organized. All isolates were subjected to broth microdilution (BMD) against 11 antimicrobial agents according to ISO 20776-1 using unsupplemented Mueller–Hinton broth on freeze-dried Sensititre panels (Thermo Scientific, UK), and most isolates (n = 371) were also tested with disc diffusion according to EUCAST methodology for non-fastidious organisms.

Results

Aggregated results were used to generate MIC and zone diameter distributions and to prepare graphs of MIC-zone diameter correlation. Based on these results, the EUCAST Steering Committee determined clinical susceptible (S) and resistant (R) MIC (mg/L) breakpoints (S≤/R>) for the five Vibrio spp. for piperacillin/tazobactam (1/1), cefotaxime (0.25/0.25), ceftazidime (1/1), meropenem (0.5/0.5), ciprofloxacin (0.25/0.25), levofloxacin (0.25/0.25), azithromycin (4/4), doxycycline (0.5/0.5) and trimethoprim/sulfamethoxazole (0.25/0.25). The corresponding zone diameter breakpoints were identified.

Conclusions

We demonstrated the validity of using standard BMD and EUCAST disc diffusion methodology for AST of five Vibrio spp., and generated suitable data to allow EUCAST to determine clinical MIC and zone diameter breakpoints for five pathogenic Vibrio spp., including both non-toxigenic and toxigenic V. cholerae.
Characteristic analysis and data comparative of linear and nonlinear low-frequency sweep in vibroseis
Authors: Zhang Jian , Zhao Guoyong , Xu Leiliang , Zhang Xu , Liu Xiaohan , Zhu Jianggui
Published: December 2023

Low-frequency seismic data plays a crucial role in seismic data processing and seismic wave inversion. At present, there are two methods to realize the low-frequency excitation of vibrators: one is exciting low-frequency vibrators by linear sweep signals, and the other is exciting conventional vibrators by nonlinear low-frequency sweep signals. The cost of exploration using low-frequency vibroseis is high, and it is challenging to obtain sufficient low-frequency information using traditional vibrators. To this end, this paper comparatively studies the low-frequency sweep signal characteristics and data effects of low-frequency and traditional vibrators. Therefore, three kinds of linear and nonlinear low-frequency sweep signal are designed. Theoretical analysis shows that there are certain differences between linear and nonlinear signal in design methods, signal shapes, etc., but after correlation calculations the signal spectra reflecting the seismic response and the related wavelet shapes are basically consistent. Besides, the actual force signal data shows that the linear and nonlinear harmonic distortion are basically equivalent. Finally, based on the forward simulation of three sweep signals and the comparative analysis of field test data, it can be considered that the linear and nonlinear low-frequency sweep signals of vibrators have almost the same denoising ability under the basic conditions of the spectrum and wavelet. Both can achieve low-frequency excitation and obtain rich low-frequency information, and the quality of seismic data is basically the same, so they can be applied in practical production.
Glucocorticoid-induced TNF receptor family–related protein functions as a costimulatory molecule for murine eosinophils
Authors: Narita Tomoya , Murakami Yusuke , Ishii Takashi , Muroi Masashi , Yamashita Naomi
Published: December 2023

Eosinophils are typical effector cells associated with type 2 immune responses and play key roles in the pathogenesis of allergic diseases. These cells are activated by various stimuli, such as cytokines, chemokines, and growth factors, but the regulatory mechanisms of eosinophil effector functions remain unclear. Glucocorticoid-induced tumor necrosis factor receptor family–related protein (GITR), a transmembrane protein belonging to the tumor necrosis factor (TNF) receptor superfamily, is a well-known regulatory molecule for T cell activation. Here, we show that GITR is also constitutively expressed on eosinophils and functions as a costimulatory molecule for these cells. Although degranulation was unaffected by GITR engagement of murine bone marrow–derived eosinophils, secretion of inflammatory cytokines such as interleukin (IL)-4, IL-6, and IL-13 from IL-33–activated bone marrow–derived eosinophils was augmented by anti-mouse GITR agonistic antibody (DTA-1). In conclusion, our results provide a new regulatory pathway of cytokine secretion from eosinophils in which GITR functions as a costimulatory molecule.
Rare cases of colonic schwannomas
Authors: Gazivoda Victor , Wang Donghai , Siddique Mustafa , Zeng Jiangying , Robert Marie E , Pantel Haddon , Mongiu Anne
Published: December 2023

Schwannomas of the gastrointestinal tract are rare spindle cell tumors that account for 2–6% of mesenchymal tumors. An elderly male was found to have a left colon mass on CT scan and colonoscopy with pathology of fibrotic tissue. A laparoscopic-assisted left hemi-colectomy with primary anastomosis was performed. Pathology demonstrated spindle cell neoplasm arranged in short fascicles that were strongly and diffusely positive for S100. An elderly female was found to have a submucosal lesion on surveillance colonoscopy in the proximal transverse colon. Biopsy with jumbo forceps revealed spindle cell neoplasm positive for S100. Patient underwent an uncomplicated limited non-oncologic segmental transverse colectomy. We report only the ninth case of left and sixth in the transverse colon described in the literature. As is true for other mesenchymal tumors, mucosal biopsy is usually inconclusive and deep biopsy or submucosal resection is required, making pre-operative surgical decision difficult.
The role of metabolomics in informing strategies for improving photosynthesis
Authors: Westhoff Philipp , Weber Andreas P M
Published: December 2023

Photosynthesis plays a vital role in acclimating to and mitigating climate change, providing food and energy security for a population that is constantly growing, and achieving an economy with zero carbon emissions. A thorough comprehension of the dynamics of photosynthesis, including its molecular regulatory network and limitations, is essential for utilizing it as a tool to boost plant growth, enhance crop yields, and support the production of plant biomass for carbon storage. Photorespiration constrains photosynthetic efficiency and contributes significantly to carbon loss. Therefore, modulating or circumventing photorespiration presents opportunities to enhance photosynthetic efficiency. Over the past eight decades, substantial progress has been made in elucidating the molecular basis of photosynthesis, photorespiration, and the key regulatory mechanisms involved, beginning with the discovery of the canonical Calvin–Benson–Bassham cycle. Advanced chromatographic and mass spectrometric technologies have allowed a comprehensive analysis of the metabolite patterns associated with photosynthesis, contributing to a deeper understanding of its regulation. In this review, we summarize the results of metabolomics studies that shed light on the molecular intricacies of photosynthetic metabolism. We also discuss the methodological requirements essential for effective analysis of photosynthetic metabolism, highlighting the value of this technology in supporting strategies aimed at enhancing photosynthesis.
Re-energization of AGN head–tail radio galaxies in the galaxy cluster ZwCl 0634.1+47474
Authors: Lusetti G , de Gasperin F , Cuciti V , Brüggen M , Spinelli C , Edler H , Brunetti G , van Weeren R J , Botteon A , Di Gennaro G , Cassano R , Tasse C , Shimwell T W
Published: December 2023

Low-frequency radio observations show an increasing number of radio galaxies located in galaxy clusters that display peculiar morphologies and spectral profiles. This is the result of the dynamical interaction of the galaxy with the surrounding medium. Studying this phenomenon is key to understanding the evolution of low-energy relativistic particles in the intracluster medium. We present a multifrequency study of the three head–tail (HT) radio galaxies and the radio halo in the galaxy cluster ZwCl 0634.1+4747. We make use of observations at four frequencies performed with LOFAR LBA (53 MHz), HBA (144 MHz), GMRT (323 MHz), and VLA (1518 MHz) data. The use of extremely low radio frequency observations, such as LOFAR at 53 and 144 MHz, allowed us to detect the extension of the tails up to a distance of ∼1 Mpc. We extracted spectral profiles along the tails in order to identify possible departures from a pure ageing model, such as the Jaffe–Perola (JP) model, which only involves synchrotron and inverse-Compton losses. We found clear evidence of departures from this simple ageing model, such as surface brightness enhancement and spectral flattening along all of the tails. This can be interpreted as the consequence of particle re-acceleration along the tails. Possible explanations for this behaviour include the interaction between a shock and the radio tails or a turbulence-driven re-acceleration mechanism. We show that the latter scenario is able to reproduce the characteristic features that we observed in our profiles.
An analytical theory for the resolution attainable using eclipse mapping of exoplanets
Authors: Boone Sasha , Grant David , Hammond Mark
Published: December 2023

We present an analytical theory for the resolution attainable via eclipse mapping of exoplanets, based on the Fourier components of the brightness distribution on the planetary disc. We find that the impact parameter determines which features can and cannot be seen, via the angle of the stellar edge relative to the axis of the orbit during the eclipse. We estimate the signal-to-noise ratio as a function of mapping resolution, and use this to determine the attainable resolution for a given star–planet system. We test this theory against numerical simulations and find good agreement; in particular, our predictions for the resolution as a function of stellar edge angle are accurate to the simulated data to within 10 per cent over a wide range of angles. Our prediction for the number of spatial modes that can be constrained given a light-curve error is similarly accurate. Finally, we give a list of exoplanets with the best expected resolution for observations with the NIRISS SOSS, NIRSpec G395H, and MIRI LRS instruments on JWST.
Twenty red giants with magnetic fields: a detailed analysis of their chemical composition
Authors: Lyubimkov L S , Korotin S A , Petrov D V , Poklad D B
Published: December 2023

We determined the fundamental parameters and analysed the chemical composition for 20 G and K giants within 150 pc from the Sun, for which the magnetic fields Bmax from 0.3 to 98.6 G have been detected. Abundances of 18 chemical elements from lithium (Z = 3) to hafnium (Z = 72) are derived. From infrared CN molecular lines, the nitrogen abundance and the carbon isotope ratio 12C/13C are determined. The low values 12C/13C = 7–26 for most of the giants prove that they were passed through the deep convecting mixing during the first dredge-up (FDU) evolutionary phase. Lithium is detected in spectra of 16 of 20 giants studied. The presence of lithium in atmospheres of giants passed through the deep mixing during the FDU phase contradicts the theory. The pronounced correlation between the [N/C] and [N/O] values is found, which has an evolutionary nature. A comparison of this relation with theoretical models calculated for rotating stars shows that it reflects mainly the dependence of these two values on the initial rotational velocity. The total C + N + O abundance that should be constant during the star’s evolution is found to be correlated with [Fe/H]. This correlation can be explained partially by the known [O/Fe] versus [Fe/H] relation. The anticorrelation between the [El/Fe] and [Fe/H] values for rare earth (RE) elements is obtained. The relations for both the sum C + N + O and the RE elements reflect the initial chemical composition of the giants. No marked systematic differences in the element abundances are found between the magnetic and non-magnetic giants.
Integrated proteomics spotlight the proteasome as a therapeutic vulnerability in embryonal tumors with multilayered rosettes
Authors: Dottermusch Matthias , Biabani Ali , Lempertz Tasja , Schumann Yannis , Navolic Jelena , Godbole Shweta , Obrecht Denise , Frank Stephan , Dorostkar Mario M , Voß Hannah , Schlüter Hartmut , Rutkowski Stefan , Schüller Ulrich , Neumann Julia E
Published: December 2023

Background

Embryonal tumors with multilayered rosettes (ETMR) are rare malignant embryonal brain tumors. The prognosis of ETMR is poor and novel therapeutic approaches are desperately needed. Comprehension of ETMR tumor biology is currently based on only few previous molecular studies, which mainly focused on the analyses of nucleic acids. In this study, we explored integrated ETMR proteomics.

Methods

Using mass spectrometry, proteome data were acquired from 16 ETMR and the ETMR cell line BT183. Proteome data were integrated with case-matched global DNA methylation data, publicly available transcriptome data, and proteome data of further embryonal and pediatric brain tumors.

Results

Proteome-based cluster analyses grouped ETMR samples according to histomorphology, separating neuropil-rich tumors with neuronal signatures from primitive tumors with signatures relating to stemness and chromosome organization. Integrated proteomics showcased that ETMR and BT183 cells harbor proteasome regulatory proteins in abundance, implicating their strong dependency on the proteasome machinery to safeguard proteostasis. Indeed, in vitro assays using BT183 highlighted that ETMR tumor cells are highly vulnerable toward treatment with the CNS penetrant proteasome inhibitor Marizomib.

Conclusions

In summary, histomorphology stipulates the proteome signatures of ETMR, and proteasome regulatory proteins are pervasively abundant in these tumors. As validated in vitro, proteasome inhibition poses a promising therapeutic option in ETMR.
The diagnostic, therapeutic, and ethical impact of artificial intelligence in modern medicine
Authors: Katwaroo Arun Rabindra , Adesh Vivek Shanker , Lowtan Amrita , Umakanthan Srikanth
Published: December 2023

In the evolution of modern medicine, artificial intelligence (AI) has been proven to provide an integral aspect of revolutionizing clinical diagnosis, drug discovery, and patient care. With the potential to scrutinize colossal amounts of medical data, radiological and histological images, and genomic data in healthcare institutions, AI-powered systems can recognize, determine, and associate patterns and provide impactful insights that would be strenuous and challenging for clinicians to detect during their daily clinical practice. The outcome of AI-mediated search offers more accurate, personalized patient diagnoses, guides in research for new drug therapies, and provides a more effective multidisciplinary treatment plan that can be implemented for patients with chronic diseases. Among the many promising applications of AI in modern medicine, medical imaging stands out distinctly as an area with tremendous potential. AI-powered algorithms can now accurately and sensitively identify cancer cells and other lesions in medical images with greater accuracy and sensitivity. This allows for earlier diagnosis and treatment, which can significantly impact patient outcomes. This review provides a comprehensive insight into diagnostic, therapeutic, and ethical issues with the advent of AI in modern medicine.
The Effect of Socioeconomic Deprivation on Radiographic Deformities in Children With Blount Disease
Authors: Benes Gregory , Ghanem Diane , Badin Daniel , Greenberg Marc , Honcharuk Erin
Published: December 2023

Background:

Blount disease can occur at any time during the growth process, primarily with a bimodal distribution in children younger than 4 years old and adolescents. The disease process most commonly presents in Black adolescents, with disease severity positively correlated with obesity. Given the known associations among race, obesity, and socioeconomic status, we investigated the relationship between the degree of social deprivation and severity of lower extremity deformities among a community-based cohort with Blount disease.

Methods:

A retrospective review of hospital records and radiographs of patients with previously untreated Blount disease was conducted. Patients were classified as having early-onset or late-onset Blount disease based on whether the lower limb deformity was noted before or after the age of 4 years. The area deprivation index (ADI), a nationally validated measure that assesses socioeconomic deprivation by residential neighborhood, was calculated for each patient as a surrogate for socioeconomic status. Higher state (range: 1 to 10) or national (range: 1 to 100) ADI corresponds to increased social deprivation. Full-length standing radiographs from index clinic visits were evaluated by 2 reviewers to measure frontal plane deformity. The association of ADI with various demographic and radiographic parameters was then analyzed.

Results:

Of the 65 patients with Blount disease, 48 (74%) children were Black and 17 (26%) were non-black children. Nineteen children (32 limbs) had early-onset and 46 children (62 limbs) had late-onset disease. Black patients had significantly higher mean state (7.6 vs. 5.4, P=0.009) and national (55.1 vs. 37.4, P=0.002) ADI values than non-black patients. Patients with severe socioeconomic deprivation had significantly greater mechanical axis deviation (66 mm vs. 51 mm, P=0.008). After controlling demographic and socioeconomic factors, the results of multivariate linear regression showed that only increased body mass index (β=0.19, 95% CI: 0.12-0.26, P<.001) and state ADI (β=0.021, 95% CI: 0.01-0.53, P=.043) were independently associated with greater varus deformity.

Conclusions:

Socioeconomic deprivation was strongly associated with increased severity of varus deformity in children with late-onset Blount disease. Our analysis suggests that obesity and socioeconomic factors are the most influential with regard to disease progression.

Level of Evidence:

Level III
Pedicle Subtraction Osteotomy Versus Multilevel Anterior Lumbar Interbody Fusion and Lateral Lumbar Interbody Fusion in the Treatment of Adult Spinal Deformity
Authors: Chi Jialun , Zhang Yi , Fontaine Andrew , Zhang Zhichang , Wang Jesse , Labaran Lawal , Li Xudong
Published: December 2023

Study Design:

Retrospective cohort study.

Objective:

The aim of this study was to compare the outcomes of pedicle subtraction osteotomy (PSO) with multilevel anterior lumbar interbody fusion (ALIF) and lateral lumbar interbody fusion (LLIF) in posterior long-segment fusion.

Background:

PSO and ALIF/LLIF are 2 techniques used to restore lumbar lordosis and correct sagittal alignment, with each holding its unique advantages and disadvantages. As there are situations where both techniques can be employed, it is important to compare the risks and benefits of both.

Patients and Methods:

Patients aged 18 years or older who underwent PSO or multilevel ALIF/LLIF with posterior fusion of 7–12 levels and pelvic fixation were identified. 1:1 propensity score was used to match PSO and ALIF/LLIF cohorts for age, sex, and relevant comorbidities, including smoking status. Logistic regression was used to compare medical and surgical outcomes. Trends and costs were generated for both groups as well.

Results:

ALIF/LLIF utilization in posterior long fusion has been steadily increasing since 2010, whereas PSO utilization has significantly dropped since 2017. PSO was associated with an increased risk of durotomy (P < 0.001) and neurological injury (P = 0.018). ALIF/LLIF was associated with increased rates of postoperative radiculopathy (P = 0.005). Patients who underwent PSO had higher rates of pseudarthrosis within 1 and 2 years (P = 0.015; P = 0.010), 1-year hardware failure (P = 0.028), and 2-year reinsertion of instrumentation (P = 0.009). Reoperation rates for both approaches were not statistically different at any time point throughout the 5-year period. In addition, there were no significant differences in both procedural and 90-day postoperative costs.

Conclusions:

PSO was associated with higher rates of surgical complications compared with anterior approaches. However, there was no significant difference in overall reoperation rates. Spine surgeons should select the optimal technique for a given patient and the type of lordotic correction required.
Hospital Course and Complications of Subaxial Cervical Trauma Patients With Tetraplegia or Paraplegia
Authors: Scott Maxwell M. , Patel Dil V. , Lucasti Christopher , Vallee Emily K. , Clark Lindsey D. , Kowalski Joseph M.
Published: December 2023

Study Design:

A single-institution, retrospective cohort study

Objective:

The objective was to present demographic characteristics, mechanism of injuries, lengths of stay, intensive care unit (ICU) days, discharge locations, and causes of 90-day readmission for patients with subaxial spinal cord injuries resulting in paraplegia or tetraplegia.

Summary of Background Data:

Spinal cord injuries resulting in paraplegia or tetraplegia are rare injuries with debilitating outcomes. Numerous advances have occurred in caring for these patients, but patients still experience multiple complications. The severity of these injuries and numerous complications result in prolonged hospital stays and the need for extensive rehabilitation.

Methods:

Twelve patients with subaxial spinal cord injury resulting in paraplegia or tetraplegia from a level 1 adult trauma center were reviewed. The primary outcomes included hospital length of stay, ICU days, intrahospital complications, 90-day readmission rates, and discharge location. We reviewed the literature for these outcomes in spinal cord injuries.

Results:

For patients with subaxial spinal cord injuries resulting in paraplegia and tetraplegia, the average age was 36.0 years, and most were male [91.7% (11/12)]. The most common mechanism of injury was gunshot wounds[41.7% (5/12)]. Patients spent an average of 46.3 days in the hospital and 30.7 days in the ICU. Respiratory complications were the most common (9 patients). Fifty percent of patients (6/12) were discharged to the inpatient spinal cord rehab center, and 16.7% (2/12) expired while in the hospital. Two patients (20.0%) were readmitted within 90 days of discharge.

Conclusions:

Most patients with subaxial spinal cord injuries resulting in paraplegia or tetraplegia were young males with high-energy traumas. Many patients had intrahospital complications, and most were discharged to the hospital spinal rehab center. These findings likely stem from the severity of paraplegia and tetraplegia injuries and the need for rehabilitation.
Pharmacokinetic Variability of Sulthiame: The Impact of Age, Drug–Drug Interactions, and Biochemical Markers of Toxicity in Patients with Epilepsy
Authors: Heger Katrine , Kjeldstadli Kari , Ring Nelly , Aaberg Kari Modalsli , Kjeldsen Signe Flood , Burns Margrete Larsen , Johannessen Svein I. , Johannessen Landmark Cecilie
Published: December 2023

Purpose:

Sulthiame is an antiseizure medication increasingly used for epilepsy. The aim of this study was to investigate the pharmacokinetic variability of sulthiame in children and adults with epilepsy with respect to age, comedication, dose, serum concentration, and biochemical markers of toxicity in a clinical setting.

Method:

Retrospective quantitative data from the therapeutic drug monitoring (TDM) database at the Section for Clinical Pharmacology, the National Center for Epilepsy, Norway (2015–2021), were used.

Results:

TDM data from 326 patients (127 female/199 male) were included [mean age, 11.4 (range 2–44) years; mean weight, 41 (range 14–109) kg]. Interindividual pharmacokinetic variability in the concentration/(dose/body weight) (C/(D/kg)) ratio was 16-fold; intraindividual variability was up to 8-fold (coefficient of variation = 10%–78%). Young children (younger than 6 years) had a significantly lower C/(D/kg) ratio than older age groups (P < 0.05). Various comedications did not significantly affect the C/(D/kg) ratio, possibly owing to the small sample size. However, CYP2C19-mediated inhibition by sulthiame was indicated because patients using clobazam and sulthiame (n = 28) had a 3.5-fold higher N-desmethylclobazam C/(D/kg) ratio than those using neutral comedication (n = 45; P < 0.001). Patients with pH values below the adjusted normal range (7.32–7.42; n = 15) had a 33% higher sulthiame concentration than those with normal pH values (n = 22; P < 0.05). Blood gas measurements, especially pH, may serve as markers of toxicity and can be used in combination with clinical data when toxicity is suspected.

Conclusions:

This study revealed the extensive intraindividual and interindividual pharmacokinetic variability of sulthiame, with age as a contributing factor. Sulthiame has clinically relevant interactions with clobazam. The use of TDM and pH as a biochemical marker may contribute to individualized and safe sulthiame treatment.
Bronchoscopic Electrocautery Versus Adrenaline and Cold Saline Instillation for Prophylactic Haemostasis Prior to Biopsy of Endobronchial Lesions (BEVACS)
Authors: Shahul S Aneesa , Chauhan Nishant Kumar , Dutt Naveen , Chakraborti Amartya , Elhence Poonam , Jalandra Ramniwas
Published: December 2023

Background:

Flexible bronchoscopy-guided endobronchial biopsy (EBB) is routinely performed as an outpatient daycare procedure. Bleeding after EBB is a common complication, that at times disrupts the procedure and can rarely lead to a catastrophe. We aimed to compare the efficacy of prebiopsy prophylactic bronchoscopic electrocautery with adrenaline and cold saline instillation in achieving hemostasis in patients with endobronchial lesions with a higher risk of bleeding during EBB.

Methods:

In this open-label, randomized controlled trial, 60 patients with endobronchial lesions were randomized to either the prophylactic electrocautery arm or the adrenaline and cold saline arm. Postbiopsy endobronchial bleed was quantified in millimeters using the Visual Analog Scale (VAS) and graded as per the British Thoracic Society grading system. Electrocautery-induced tissue damage was graded by the pathologist as “no damage,” “mild,” “moderate,” and “severe.”

Results:

The median VAS score of bleeding was 6.14 mm (interquartile range: 8 mm) in the electrocautery arm and 10.17 mm (interquartile range: 7 mm) in the adrenaline and cold saline arm. Though the difference in the VAS score of bleeding between the two groups was statistically significant, there was no significant difference in the proportion of grade 2 or higher bleeding.

Conclusion:

No difference in postbiopsy bleed was observed between the application of electrocautery or instillation of cold saline plus adrenaline before biopsy of those endobronchial lesions which were likely to bleed more after biopsy. Although controlled prophylactic electrocautery using 15 watts did not impair the quality of EBB specimens, a higher wattage may change this observation, as well as the bleeding quantity.
Effectiveness of Integrated Mindfulness-Based Fitness Training Program in Ameliorating Physical Symptoms and Survivor Concerns in Patients With Breast Cancer
Authors: Chang Yun-Chen
Published: December 2023

Background

Patients with breast cancer typically experience both mental and physical distress after aggressive treatments. Some studies have explored the use of integrated interventions, such as mindfulness-based or exercise-based approaches, to reduce these symptoms. However, the results of these studies have been conflicting.

Objective

The aim of this study was to evaluate the effectiveness of an integrated mindfulness-based fitness training (MBFT) program in addressing overactive bladder, fear of cancer recurrence, and female sexual function in patients with breast cancer.

Methods

Fifty patients with breast cancer were either assigned to an 8-week MBFT group or a waitlist control group. The postintervention and preintervention scores were compared using descriptive analysis of the data set, as well as paired and independentttests.

Results

There was no significant improvement in overactive bladder symptoms. Significant differences were observed in survivor concerns for items related to future diagnostic tests (t= 2.667,P= .024; 95% confidence interval [CI], 0.120–1.335), another type of cancer (t= 2.667,P= .024; 95% CI, 0.120–1.335), cancer coming back (t= 4.183,P= .002; 95% CI, 0.297–0.975), dying (t= 2.609,P= .026; 95% CI, 0.093–1.180), and my health (t= 2.887,P= .016; 95% CI, 0.104–0.805). A significant difference was found in the item measuring overall sexual life satisfaction (t= −3.162,P= .013) and sexual desire (MBFT vs waitlist control group, 2.00 vs 1.18;P= .023).

Conclusion

Mindfulness-based fitness training interventions were effective in enhancing the well-being of patients with breast cancer by reducing fear of recurrence and enhancing sexual function. These findings support the use of MBFT as complementary therapy.

Implications for Practice

Healthcare providers should carefully assess the individual needs and preferences of each patient and tailor interventions accordingly. In addition, integrating multiple approaches may be more effective in reducing distress.
Causal association of the brain structure with the risk of knee osteoarthritis: A large-scale genetic correlation study
Authors: Ruan Zhe , Lin Shaohai , Liu Zhi , Chen Peng , Xie Tongtong , Meng Li , Long Haitao , Zhao Shushan
Published: December 2023

Objectives

Observational studies have shown the association between knee osteoarthritis (KOA) and neurological disorders with alterations in brain imaging-derived phenotypes (BIDPs). This study aimed at investigating whether alterations in brain structure are correlated with the occurrence of KOA.

Methods

Based on the summary data from two large scale genome-wide association studies (GWASs), we performed a bidirectional two-sample Mendelian randomization (MR) analysis using single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to determine the potential causal relationships between KOA and BIDPs.

Results

We identified the genetic correlations of 152 BIDPs with KOA using linkage disequilibrium score regression. MR analysis revealed that increased volume but decreased intensity-contrast of bilateral nucleus accumbens (NAc), as well as increased left paracentral area was positively causally associated with KOA risk. For the IDPs of structural connectivity, we identified causal associations between multiple increased DTI parameter indicators of corticospinal tract (CST) and KOA. Inversely, KOA was positively correlated with the thickness and intensity-contrast of the rostral anterior cingulate, as well as the intensity-contrast of caudal anterior cingulate, insula cortex, and the grey matter volume of pallidum.

Conclusion

Our study supported bidirectional causal associations between KOA and BIDPs, which may provide new insights into the interaction of KOA with structural alterations in the nervous system.