bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellenium—a scalable and interactive visual analytics app for exploring multimodal single-cell data
Authors: Jahn Carsten , Ibrahim Mahmoud , Busch Jannis , Lin Qiong , Manchanda Himanshu , Mohr Hagen , Plischke Dan , Roider Helge G , Steffen Andreas
Published: May 2023

Multimodal single-cell sequencing data provide detailed views into the molecular biology of cells. To allow for interactive analyses of such rich data and to readily derive insights from it, new analysis solutions are required. In this work, we present Cellenium, our new scalable visual analytics web application that enables users to semantically integrate and organize all their single-cell RNA-, ATAC-, and CITE-sequencing studies. Users can then find relevant studies and analyze single-cell data within and across studies. An interactive cell annotation feature allows for adding user-defined cell types.

Availability and implementation

Source code and documentation are freely available under an MIT license and are available on GitHub (https://github.com/Bayer-Group/cellenium). The server backend is implemented in PostgreSQL, Python 3, and GraphQL, the frontend is written in ReactJS, TypeScript, and Mantine css, and plots are generated using plotlyjs, seaborn, vega-lite, and nivo.rocks. The application is dockerized and can be deployed and orchestrated on a standard workstation via docker-compose.
MRGCN: cancer subtyping with multi-reconstruction graph convolutional network using full and partial multi-omics dataset
Authors: Yang Bo , Yang Yan , Wang Meng , Su Xueping
Published: May 2023

Motivation

Cancer is a molecular complex and heterogeneous disease. Each type of cancer is usually composed of several subtypes with different treatment responses and clinical outcomes. Therefore, subtyping is a crucial step in cancer diagnosis and therapy. The rapid advances in high-throughput sequencing technologies provide an increasing amount of multi-omics data, which benefits our understanding of cancer genetic architecture, and yet poses new challenges in multi-omics data integration.

Results

We propose a graph convolutional network model, called MRGCN for multi-omics data integrative representation. MRGCN simultaneously encodes and reconstructs multiple omics expression and similarity relationships into a shared latent embedding space. In addition, MRGCN adopts an indicator matrix to denote the situation of missing values in partial omics, so that the full and partial multi-omics processing procedures are combined in a unified framework. Experimental results on 11 multi-omics datasets show that cancer subtypes obtained by MRGCN with superior enriched clinical parameters and log-rank test P-values in survival analysis over many typical integrative methods.

Availability and implementation

https://github.com/Polytech-bioinf/MRGCN.git https://figshare.com/articles/software/MRGCN/23058503.
Microchromosome fusions underpin convergent evolution of chameleon karyotypes
Authors: Mezzasalma Marcello , Streicher Jeffrey W , Guarino Fabio M , Jones Marc E H , Loader Simon P , Odierna Gaetano , Cooper Natalie
Published: May 2023

Evolutionary shifts in chromosome compositions (karyotypes) are major drivers of lineage and genomic diversification. Fusion of ancestral chromosomes is one hypothesized mechanism for the evolutionary reduction of the total chromosome number, a frequently implied karyotypic shift. Empirical tests of this hypothesis require model systems with variable karyotypes, known chromosome features, and a robust phylogeny. Here we used chameleons, diverse lizards with exceptionally variable karyotypes ($2n=20\text{-}62$), to test whether chromosomal fusions explain the repeated evolution of karyotypes with fewer chromosomes than ancestral karyotypes. Using a multidisciplinary approach including cytogenetic analyses and phylogenetic comparative methods, we found that a model of constant loss through time best explained chromosome evolution across the chameleon phylogeny. Next, we tested whether fusions of microchromosomes into macrochromosomes explained these evolutionary losses using generalized linear models. Multiple comparisons supported microchromosome fusions as the predominant agent of evolutionary loss. We further compared our results to various natural history traits and found no correlations. As such, we infer that the tendency of microchromosomes to fuse was a quality of the ancestral chameleon genome and that the genomic predisposition of ancestors is a more substantive predictor of chromosome change than the ecological, physiological, and biogeographical factors involved in their diversification.
A thiamine transporter is required for biofilm formation by Rhizobium sp. IRBG74
Authors: Ketelboeter Laura M , Mitra Shubhajit , Gyaneshwar Prasad
Published: May 2023

Rhizobium sp. IRBG74 is a nitrogen-fixing symbiont of Sesbania cannabina and a growth-promoting endophyte of rice, thus making it a good model to compare rhizobial interactions with legumes and cereals. In this report, we show that Rhizobium sp. IRBG74 forms biofilms on the roots of S. cannabina and rice. A mutant defective in biofilm formation was identified by screening a transposon mutant library. The transposon insertion was in thiQ, part of the thiBPQ operon that encodes the components of a thiamine/thiamine pyrophosphate ABC transporter. Complementation with thiBPQ partially restored biofilm formation. Addition of thiamine in growth media led to repression of thiC expression in the wild-type strain but not in the thiQ mutant. These results suggest that thiBPQ is involved in thiamine/TPP transport in Rhizobium sp. IRBG74. Using a GUS reporter, we show that the expression of thiC is significantly higher in biofilm as compared to cells in planktonic growth. Based on these results, we propose that Rhizobium sp. IRBG74 is thiamine-limited and requires thiamine transport for efficient biofilm formation and plant colonization. Thiamine synthesis in aerobic bacteria such as Rhizobium requires O2 and thus could be inhibited in the microaerobic/anaerobic conditions in biofilms.
Sequence-based mutation patterns at 41 Y chromosomal STRs in 2 548 father–son pairs
Authors: Liu Ze , Long Guannan , Lang Yubo , Liu Dahua , Zhang Biao , Yu Shaobo , Guo Fei
Published: May 2023

A total of 2 548 unrelated healthy father–son pairs from a Northern Han Chinese population were genotyped at 41 Y chromosomal short tandem repeat (Y-STRs) including DYS19, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS444, DYS447, DYS448, DYS449, DYS456, DYS458, DYS460, DYS481, DYS518, DYS522, DYS549, DYS533, DYS557, DYS570, DYS576, DYS593, DYS596, DYS627, DYS635, DYS643, DYS645, Y-GATA-H4, DYF387S1a/b, DYF404S1a/b, DYS385a/b, and DYS527a/b. In 2 548 father samples, 2 387 unique haplotypes were detected with the haplotype diversity and discrimination capacity values of 0.999 956 608 and 0.96 741 007. The average gene diversity (GD) value was 0.6934 with a range from 0.1051 at DYS645 to 0.9657 at DYS385a/b. When comparing alleles at 24 overlapped Y-STRs between the ForenSeq™ deoxyribonucleic acid (DNA) Signature Prep Kit on the MiSeq FGx® Forensic Genomics System and the Goldeneye® DNA ID Y Plus Kit on the Applied Biosystems™ 3730 DNA Analyzer from 308 father samples in mutational pairs, 258 alleles were detected by massively parallel sequencing (MPS) typing including 156 length-based alleles that could be obtained by capillary electrophoresis (CE) typing, 95 repeat region (RR) variant alleles and seven flanking region variant alleles. Hereof, we found 16 novel RR variant alleles and firstly identified two SNPs (rs2016239814 at DYS19 and rs2089968964 at DYS448) and one 4-bp deletion (rs2053269960 at DYS439) that had been validated by the Database of Short Genetic Variation. Sanger sequencing or MPS was employed to confirm 356 mutations from 104 468 allele transfers generated from CE, where 96.63% resulted in one-step mutations, 2.25% in two-step, and 1.12% in multi-step, and the overall ratio of repeat gains versus losses was balanced (173 gains vs. 183 losses). In 308 father–son pairs, 268 pairs occurred mutations at a single locus, 33 pairs at two loci, six pairs at three loci, and one pair at four loci. The average Y-STR mutation rate at 41 Y-STRs was ⁓3.4 × 10−3 (95% confidence intervals: 3.1 × 10−3–3.8 × 10−3). The mutation rates at DYS576 and DYS627 were higher than 1 × 10−2 in Northern Han Chinese, whilst the mutation rates at DYF387S1a/b, DYF404S1a/b, DYS449, DYS518, and DYS570 were lower than initially defined. In this study, the classical molecular factors (the longer STR region, the more complex motif and the order father) were confirmed to drive Y-STR mutation rates increased, but the length of repeat unit did not conform to the convention. Lastly, the interactive graphical and installable StatsY was developed to facilitate forensic scientists to automatically calculate allele and haplotype frequencies, forensic parameters, and mutation rates at Y-STRs.

Key points
Forages and pastures symposium: forage biodegradation: advances in ruminal microbial ecology
Authors: Osorio-Doblado A M , Feldmann K P , Lourenco J M , Stewart R L , Smith W B , Tedeschi L O , Fluharty F L , Callaway T R
Published: May 2023

The rumen microbial ecosystem provides ruminants a selective advantage, the ability to utilize forages, allowing them to flourish worldwide in various environments. For many years, our understanding of the ruminal microbial ecosystem was limited to understanding the microbes (usually only laboratory-amenable bacteria) grown in pure culture, meaning that much of our understanding of ruminal function remained a “black box.” However, the ruminal degradation of plant cell walls is performed by a consortium of bacteria, archaea, protozoa, and fungi that produces a wide variety of carbohydrate-active enzymes (CAZymes) that are responsible for the catabolism of cellulose, hemicellulose, and pectin. The past 15 years have seen the development and implementation of numerous next-generation sequencing (NGS) approaches (e.g., pyrosequencing, Illumina, and shotgun sequencing), which have contributed significantly to a greater level of insight regarding the microbial ecology of ruminants fed a variety of forages. There has also been an increase in the utilization of liquid chromatography and mass spectrometry that revolutionized transcriptomic approaches, and further improvements in the measurement of fermentation intermediates and end products have advanced with metabolomics. These advanced NGS techniques along with other analytic approaches, such as metaproteomics, have been utilized to elucidate the specific role of microbial CAZymes in forage degradation. Other methods have provided new insights into dynamic changes in the ruminal microbial population fed different diets and how these changes impact the assortment of products presented to the host animal. As more omics-based data has accumulated on forage-fed ruminants, the sequence of events that occur during fiber colonization by the microbial consortium has become more apparent, with fungal populations and fibrolytic bacterial populations working in conjunction, as well as expanding understanding of the individual microbial contributions to degradation of plant cell walls and polysaccharide components. In the future, the ability to predict microbial population and enzymatic activity and end products will be able to support the development of dynamic predictive models of rumen forage degradation and fermentation. Consequently, it is imperative to understand the rumen’s microbial population better to improve fiber degradation in ruminants and, thus, stimulate more sustainable production systems.
Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature
Authors: Jackson Heather R , Miglietta Luca , Habgood-Coote Dominic , D’Souza Giselle , Shah Priyen , Nichols Samuel , Vito Ortensia , Powell Oliver , Davidson Maisey Salina , Shimizu Chisato , Agyeman Philipp K A , Beudeker Coco R , Brengel-Pesce Karen , Carrol Enitan D , Carter Michael J , De Tisham , Eleftheriou Irini , Emonts Marieke , Epalza Cristina , Georgiou Pantelis , De Groot Ronald , Fidler Katy , Fink Colin , van Keulen Daniëlle , Kuijpers Taco , Moll Henriette , Papatheodorou Irene , Paulus Stephane , Pokorn Marko , Pollard Andrew J , Rivero-Calle Irene , Rojo Pablo , Secka Fatou , Schlapbach Luregn J , Tremoulet Adriana H , Tsolia Maria , Usuf Effua , Van Der Flier Michiel , Von Both Ulrich , Vermont Clementien , Yeung Shunmay , Zavadska Dace , Zenz Werner , Coin Lachlan J M , Cunnington Aubrey , Burns Jane C , Wright Victoria , Martinon-Torres Federico , Herberg Jethro A , Rodriguez-Manzano Jesus , Kaforou Myrsini , Levin Michael
Published: May 2023

Background

To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections.

Methods

Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39).

Results

In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%–98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%–97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV.

Conclusions

MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.
A genomic score to predict local control among patients with brain metastases managed with radiation
Authors: Lamba Nayan , Cagney Daniel N , Catalano Paul J , Kim Dewey , Elhalawani Hesham , Haas-Kogan Daphne A , Wen Patrick Y , Wagle Nikhil , Aizer Ayal A
Published: May 2023

Background

Clinical predictors of local recurrence following radiation among patients with brain metastases (BrM) provide limited explanatory power. We developed a DNA-based signature of radiotherapeutic efficacy among patients with BrM to better characterize recurrence risk.

Methods

We identified 570 patients with 1487 BrM managed with whole-brain (WBRT) or stereotactic radiation therapy at Brigham and Women’s Hospital/Dana-Farber Cancer Institute (2013–2020) for whom next-generation sequencing panel data (OncoPanel) were available. Fine/Gray’s competing risks regression was utilized to compare local recurrence on a per-metastasis level among patients with versus without somatic alterations of likely biological significance across 84 genes. Genes with a q-value ≤ 0.10 were utilized to develop a “Brain-Radiation Prediction Score” (“Brain-RPS”).

Results

Genomic alterations in 11 (ATM, MYCL, PALB2, FAS, PRDM1, PAX5, CDKN1B, EZH2, NBN, DIS3, and MDM4) and 2 genes (FBXW7 and AURKA) were associated with decreased or increased risk of local recurrence, respectively (q-value ≤ 0.10). Weighted scores corresponding to the strength of association with local failure for each gene were summed to calculate a patient-level RPS. On multivariable Fine/Gray’s competing risks regression, RPS [1.66 (1.44–1.91, P < .001)], metastasis-associated edema [1.60 (1.16–2.21), P = .004], baseline size [1.02 (1.01–1.03), P < .001] and receipt of WBRT without local therapy [4.04 (2.49–6.58), P < .001] were independent predictors of local failure.

Conclusions

We developed a genomic score to quantify local recurrence risk following brain-directed radiation. To the best of our knowledge, this represents the first study to systematically correlate DNA-based alterations with radiotherapeutic outcomes in BrM. If validated, Brain-RPS has potential to facilitate clinical trials aimed at genome-based personalization of radiation in BrM.
A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequentialnab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer
Authors: Yang Ji-Xin , Yang Yu-Qing , Hu Wen-Yu , Yang Lu , Wu Jiang , Wen Xin-Xin , Yu Jing , Huang Mei-Ling , Xu Dong-Dong , Tie Dan-Chen , Wang Lei , Li Fan-Fan , Li Nan-Lin
Published: May 2023

Background

Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP).

Patients and Methods

Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR).

Results

Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = .01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = .02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107).

Conclusion

Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.
Immune-mediated diseases and risk of incident cardiovascular diseases: a prospective cohort study
Authors: Yu Yuetian , Sun Ying , Wang Yuying , Yu Yuefeng , Wang Bin , Chen Chi , Tan Xiao , Lu Yingli , Wang Ningjian
Published: May 2023

Objectives

Disorders of immune system may impact cardiovascular health; however, comprehensive study is lacking. We aimed to analyse the association of total and 20 individual immune-mediated diseases (IMDs) with risk of incident cardiovascular disease (CVD).

Methods

In this prospective cohort study, 414 495 participants (55.6% women; mean age 55.9 years) from UK Biobank with baseline assessment at 2006–10 were included. Among them, 21 784 participants had prevalent IMDs. Information on IMDs at baseline and incidence of CVDs during follow-up were recorded. Cox proportional hazard models were used to estimate the association between IMDs and CVDs risk.

Results

During the median follow-up of 12.1 years, there were 6506 cases of CVDs in participants with IMDs (29.9%) and 77 699 cases in those without IMDs (19.8%). After multivariable adjustment, participants with IMDs were significantly associated with an increased risk of total CVD [hazard ratio (HR) 1.57; 95% CI 1.52–1.61]. Among the 20 IMDs, 16 showed significant associations with CVD (all P < 0.0025 after Bonferroni correction), with HR ranging from 1.34 (1.16–1.54) for celiac disease to 2.75 (2.10–3.61) for SLE. Participants with any IMD exposure had a higher risk of all individual CVD events, with HR ranging from 1.34 (1.14–1.58) for cerebral hemorrhage to 1.80 (1.54–2.11) for pericardium diseases. IMD duration <5, 5–10 and >10 years was associated with 55%, 59% and 56% increased risk of total CVD, respectively.

Conclusion

Total and individual IMDs were associated with an increased risk of overall CVDs. It is important to consider primary prevention of CVD in patients with IMD and dysregulation of immune system in the cardiovascular health.
Belgian court of appeal rules on inheritance tax treatment of a distribution by a Liechtenstein foundation
Authors: Appermont Niels
Published: May 2023

In a judgment of 5 April 2022, the Court of Appeal of Ghent ruled on a case regarding the qualification of a distribution by Liechtenstein Stiftung under Belgian inheritance taxation. While the constitution of and the transfer of assets to a private foundation, or even a distribution by a private foundation after the death of the founder normally does not trigger Belgian inheritance taxation, the Court ultimately ruled that the distributions should be subject to inheritance taxation, based on the (perceived) existence of an ‘agreement’ between the wife of the founder, who was designated as the ‘first beneficiary’ and the second beneficiaries. This judgment raises a number of questions regarding the correct interpretation of the relevant Belgian tax provisions and the correct application of the applicable Liechtenstein legislation. This article provides an in-depth assessment of this judgment and serves as a cautionary tale for any private foundation which has a founder and/or beneficiaries resident in Belgium.
Casein and pea enriched high-protein diet attenuates arsenic provoked apoptosis in testicles of adult rats
Authors: Biswas Sagnik , Pal Priyankar , Mondal Rubia , Mukhopadhyay Prabir Kumar
Published: May 2023

Arsenic toxicity is a major health issue that also threats male reproductive system leading to impairment of fertility. The antioxidant capacity of casein and pea enriched formulated high-protein diet (FHPD) is found to be effective in different toxicity management. The present study was endeavored to investigate the mitigatory aspect of FHPD on arsenic stimulated testicular apoptosis. Adult male rats were maintained on either normal diet as control (Gr I, n = 8) and arsenic (As2O3) treated at a dose of 3 mg/kg/rat/day (Gr II, n = 8) or on isocaloric FHPD as supplemented (Gr III, n = 8) with same dose of arsenic for 30 consecutive days. Testicular histomorphometry, spermatokinetics, testicular functional marker enzymes, serum gonadotrophins, oxidative stress markers, testicular deoxyribonucleic acid (DNA) damage, and apoptosis markers were evaluated to assess the reprotoxicity of arsenic and subsequent protection by FHPD. FHPD protected the histopathological alterations and also restored normal spermatogenesis. Altered enzymatic activities of testicular functional markers like lactate dehydrogenase, γ-glutamyl transferase, acid phosphatase, and alkaline phosphatase were also regularized. FHPD also reinstated the normal level of follicle stimulating hormone (FSH), luteinising hormone (LH), and also normalized the enzymatic activities of testicular glutathione peroxidase and glutathione reductase. Testicular DNA damage was also prevented by FHPD supplementation. Testicular apoptosis marked by the altered messenger ribonucleic acid and protein expression of apoptotic markers like Bax, Bcl-2, caspase 9, and caspase 3 were also attenuated upon FHPD supplementation along with diminution of arsenic accumulation in testicular tissues. FHPD not only mitigated the adverse effects of arsenic induced gonadotoxicity but also helped in sustaining the normal reproductive functions.
Comparison of Clinical Prediction Rules in Pre-school Aged Children With Septic Hip Arthritis Due to Different Pathogens
Authors: Hagedoorn Nienke N. , Olijve Laudi , Kang Laurant , Walls Tony , Davis Joshua
Published: May 2023

Background:

Although differentiating between transient synovitis and septic hip arthritis is challenging, clinical prediction rules such as the Kocher criteria (KC) have been shown to help with the diagnosis of septic hip arthritis in children. Their performance in septic arthritis due to less virulent pathogens such as Kingella Kingae, however is unknown. We aimed to describe the performance of these clinical prediction rules in pre-school children with septic hip arthritis due to different pathogens. We hypothesised that the number of KC or modified KC met would be lower in children with septic hip arthritis caused by K. kingae, compared to those caused by Staphylococcus aureus.

Methods:

In this retrospective multicentre study conducted in Australia and New Zealand between 2012-2016, we included children with confirmed septic hip arthritis due to S. aureus (n=29), K. kingae (n=20), other pathogens (n=32), and no pathogen identified (n=48). We applied the KC (temperature, weight-bearing, erythrocyte sedimentation rate, white blood cell count) and the modified KC (C-reactive protein added) and assessed their sensitivity for septic hip arthritis, using cut offs of KC ≥ 3 and modified KC ≥ 4.

Results:

The score of the KC and the modified KC was not lower in K. kingae compared to S. aureus (P=0.27, P=0.21). In addition, both the sensitivity for the KC (S. aureus 18/29 (62.1%); K. kingae 12/20 (60.0%)), and for the modified KC (S. aureus 18/29 (62.1%); K. kingae 12/20 (60.0%)) did not differ between K. kingae and S. aureus. Of all children with septic hip arthritis, the sensitivity of both the KC and modified KC were 56.6% (95%CI 47.6-65.3).

Conclusions:

The clinical prediction rules had comparable performance in K. kingae infections to those caused by S. aureus. Concerningly, less than 60% of the children with confirmed septic hip arthritis met the cut-off values. These prediction rules lack sensitivity to rule-out septic hip arthritis in the early assessment of pre-school aged children with acute hip pain.

Level of Evidence:

Level III Diagnostic.
Hemiepiphysiodesis for Lower Extremity Coronal Plane Angular Correction in the Distal Femur and Proximal Tibia in Children With Achondroplasia
Authors: Makarewich Christopher A. , Zhang Emily , Stevens Peter M.
Published: May 2023

Background:

Achondroplasia is the most prevalent form of skeletal dysplasia, affecting more than 250,000 individuals. Lower extremity angular deformities, particularly genu varum, are common in children with achondroplasia, often resulting in pain and limitation of function. The authors aim to determine the utility of lower extremity growth modulation with hemiepiphysiodesis in children with achondroplasia for correction of coronal plane deformities about the knee.

Methods:

The authors performed a retrospective chart review of a single center from 1/1/2000 to 12/31/2020 to identify pediatric patients with achondroplasia treated with hemiepiphysiodesis as their initial procedure at the distal femur and/or proximal tibia. Patients with adequate records and who had completed their treatment were included. Data collected included duration of treatment, complications, need for osteotomy, and radiographic measurements including initial and final mechanical axis deviation, knee mechanical axis zone, mechanical lateral distal femoral angle and medial proximal tibia angle.

Results:

Ten patients with 17 limbs met our criteria. Nine patients (15 limbs) were treated for genu varum and 1 patient (2 limbs) was treated for genu valgum. Prior to treatment, the mechanical axis fell in zone 3 in 59% of limbs and zone 2 in 41%. Average correction in mechanical axis deviation was 26.1 mm. Average change in mechanical lateral distal femoral angle was 10.3 degrees per limb, and average change in medial proximal tibia angle was 7.1 degrees per limb. Average treatment duration was 909 days. At final follow up, 81% (14/17) of limbs had the mechanical axis in zone 1, with the remaining 18% (3/17) in zone 2. No patient/limb underwent subsequent distal femur or proximal tibia osteotomy for coronal plane alignment.

Conclusions:

Children with achondroplasia can successfully be treated with hemiepiphysiodesis to correct coronal plane deformities at the distal femur and proximal tibia. Using this technique, no patient in our series required an osteotomy for genu varum/valgum.

Level of Evidence:

Therapeutic level IV, Case series.
A Simple Surgical Technique for Arthroscopic Repair of Traumatic Radial–Side Peripheral TFCC Tear
Authors: Shojaie Babak , Bazzi Nagham , Saremi Hossein
Published: May 2023

Conventionally, The Triangular Fibrocartilage Complex (TFCC) surgical procedures are complex in nature with open explorations and long hospital stays not to mention the added costs and the psychological stress for both the surgeon and the patient. Nowadays, surgical procedures are looked at in a different scope with the rapid progress of arthroscopic technology and equipment. To elaborate, here we introduce a simple surgical technique for arthroscopic repair of traumatic radial – side peripheral TFCC tear. In spite of the various surgical techniques found in the literature, we just used a k-wire and a couple of needles in order to repair Radial-sided peripheral TFCC tear. the simplicity of the current technique, adequate satisfaction and eliminating the use of a targeting device, is what sets this apart. For emphasis, this technique is less time consuming and is cost-effective with satisfactory result.
Diverse Drug Classes Partition into Human Sweat: Implications for Both Sweat Fundamentals and for Therapeutic Drug Monitoring
Authors: Ruwe Theresa , White Evyn , Zebertavage Aidan S. , Runnoe David , Fay Dan , Daumeyer Henry , Tracy Timothy S. , Uchtman Kara Fay , Begtrup Gavi , Yuan Yuchan , Heikenfeld Jason , Buggele William A.
Published: May 2023

Therapeutic drug monitoring to optimize drug therapy typically relies on the inconvenience of repeated plasma sampling. Sweat is a potential alternative biofluid convenient for sampling. However, limited information exists regarding the range of drugs excreted in sweat and their correlation with plasma concentrations. This study evaluated drugs in sweat and plasma of an ambulatory clinical cohort. Pilocarpine-induced sweat was collected from ambulatory participants at a single instance using an absorbent nylon mesh, followed by concurrent blood sampling for ratio and correlation analyses. In a model drug study, the pharmacokinetics of acetaminophen in sweat and plasma were compared. Of the 14 drugs and 2 metabolites monitored in the clinical study, all compounds were present in sweat and plasma; however, the sweat-to-plasma ratio varied substantially across the drugs. Opioids and methocarbamol demonstrated the highest concentrations in sweat, sometimes exceeding plasma concentrations. Selected antidepressants and muscle relaxants were also detected in sweat at a 2–10-fold dilution to the plasma. Others, such as gabapentin and pregabalin, were highly diluted (>30-fold) in sweat compared with plasma. Together, these data suggest that molecular attributes, specifically hydrophobicity (logP) and charge state at physiologic pH (7.4), enable reasonable prediction of sweat-to-plasma drug correlation. These findings demonstrated that sweat could be used as an alternative biofluid for therapeutic drug monitoring. The findings also suggest that although it has been broadly accepted that small hydrophobic molecules most likely have a strong plasma correlation, there is a small window of hydrophobicity and charge state that permits sweat partitioning.
Respiratory Coinfections in Children With SARS-CoV-2
Authors: Westbrook Adrianna , Wang Tingyu , Bhakta Kushmita , Sullivan Julie , Gonzalez Mark D. , Lam Wilbur , Rostad Christina A.
Published: May 2023

Background:

As the transmission of endemic respiratory pathogens returns to prepandemic levels, understanding the epidemiology of respiratory coinfections in children with SARS-CoV-2 is of increasing importance.

Methods:

We performed a retrospective analysis of all pediatric patients 0–21 years of age who had a multiplexed BioFire Respiratory Panel 2.1 test performed at Children’s Healthcare of Atlanta, Georgia, from January 1 to December 31, 2021. We determined the proportion of patients with and without SARS-CoV-2 who had respiratory coinfections and performed Poisson regression to determine the likelihood of coinfection and its association with patient age.

Results:

Of 19,199 respiratory panel tests performed, 1466 (7.64%) were positive for SARS-CoV-2, of which 348 (23.74%) also had coinfection with another pathogen. The most common coinfection was rhino/enterovirus (n = 230, 15.69%), followed by adenovirus (n = 62, 4.23%), and RSV (n = 45, 3.507%). Coinfections with SARS-CoV-2 were most commonly observed in the era of Delta (B.1.617.2) predominance (190, 54.60%), which coincided with periods of peak rhino/enterovirus and RSV transmission. Although coinfections were common among all respiratory pathogens, they were significantly less common with SARS-CoV-2 than other pathogens, with exception of influenza A and B. Children <2 years of age had the highest frequency of coinfection and of detection of any pathogen, including SARS-CoV-2. Among children with SARS-CoV-2, for every 1-year increase in age, the rate of coinfections decreased by 8% (95% CI, 6–9).

Conclusions:

Respiratory coinfections were common in children with SARS-CoV-2. Factors associated with the specific pathogen, host, and time period influenced the likelihood of coinfection.
HSV-1 Encephalitis Presenting with Diplopia: Effects of Infection or Autoimmunity?
Authors: Elvan-Tuz Aysegul , Kaya-Guner Emine , Sarioglu Fatma Ceren , Agrali-Eroz Nesli , Baykan Muge , Karadag-Oncel Eda , Yilmaz Dilek , Olgac-Dundar Nihal
Published: May 2023

This report describes a case in which diplopia was developed as a finding of postinfectious anti–N-methyl-d-aspartate receptor encephalitis. Infectious encephalitis, especially herpes simplex virus, is essential as it is one of the triggers of autoimmune encephalitis. Even if the cases present unexpected clinical findings, we should be vigilant in terms of autoimmune processes, such as diplopia seen in our case.
Effects of Total Intravenous Versus Inhalational Anesthesia on Bleeding During Endoscopic Ear Surgery: Preliminary Results From a Case-Control Study
Authors: Molinari Giulia , Reale Marella , Alicandri-Ciufelli Matteo , Villari Domenico , Presutti Livio , Feminò Raimondo , Fernandez Ignacio Javier , Lucidi Daniela
Published: May 2023

Objective

To assess the impact of the type of maintenance anesthesia on the bleeding conditions of the surgical field and hemodynamic parameters during endoscopic ear surgery (EES), comparing totally intravenous inhalational anesthesia (TIVA) with inhalational anesthesia (IA).

Study Design

Retrospective case-control study.

Setting

Tertiary referral center.

Patients

Fifteen consecutive EES cases performed with TIVA between 2019 and 2020 at our Institution were matched to a control group of patients who underwent EES with IA in the same period. Patients with American Society of Anesthesiologists IV grade, acute otitis before surgery, congenital or acquired coagulopathies, use of anti-inflammatory drugs, or antiaggregant or anticoagulant therapy in the 5 days before the intervention were excluded.

Interventions

Both primary and revision tympanoplasty and stapes surgery were considered.

Main Outcome Measures

Surgical videos were reviewed to quantify the entity of bleeding according to the Modena Bleeding Score. Hemodynamic parameters during surgery were retrospectively collected. A comparison between the two groups was performed.

Results

No statistically significant differences between the two groups in terms of bleeding were found at any of time point evaluated. The tympanomeatal flap elevation resulted in the bloodiest step in both groups. Hemodynamic parameters were similar in both groups (p > 0.05).

Conclusions

These preliminary data do not support a significant difference in bleeding conditions and hemodynamic parameters between EES patients receiving TIVA and those receiving IA. Further studies involving a higher number of patients will improve our understanding on how maintenance anesthesia with TIVA may be beneficial in terms of bleeding control as compared with IA for patients undergoing EES.
Lyrical Trends: An Analysis of Music’s (Mis) Use of Vertigo
Authors: Jiam Nicole T. , Chern Alexander , Watson Jowan , Naples James G.
Published: May 2023

Background

Popular culture and music have long served as windows into the common attitudes, trends, and issues of the time. The representation of vertigo in music has not been previously explored. The objective of this study was to analyze the portrayal of vertigo in music through content and sentiment analysis of song lyrics.

Methods

A large song lyric database was queried to identify English language song titles containing the word “vertigo.” A sentiment and content analysis of the lyrics was performed to delineate the most frequently used words, the accuracy of vertigo depictions, and emotional valence (i.e., the ratio of positive to negative references to vertigo).

Results

Between 1969 and 2022, there were a total of 54 songs specifically titled “Vertigo.” Most songs (73%) portrayed vertigo negatively, and the prevalence of negative sentiment within music increased with each decade. The three most common words being used in association with vertigo within music were “feel” (n = 97), “love” (n = 66), and “falling” (n = 57). In early decades, songs using the word vertigo misrepresented the condition and associated perceptions relative to common medical understanding. In more recent decades, vertigo was used in a way more representative of medical interpretations.

Conclusion

The depiction of vertigo in songs has changed over time, and more recently, usage has reflected Bárány Society definitions. Interestingly, the negative sentiment has also increased with time. This work provides a lyrical analysis of vertigo that may improve physician understanding of the cultural usage of this challenging symptom.
Functional Status and Quality of Life 6 Months After Extracorporeal Membrane Oxygenation Therapy for COVID-19-Related Pulmonary Failure
Authors: Guenther Sabina P. W. , Cheaban Rayan , Hoepner Lisa , Weinrautner Nicole , Kirschning Thomas , Al-Khalil Riad , Bruenger Frank , Serrano Maria R. , Barndt Iris , Wiemer Marcus , Niedermeyer Jost , Rudloff Markus , Helms Sven , Schramm René , Gummert Jan F.
Published: May 2023

Extracorporeal membrane oxygenation (ECMO) is increasingly used in COVID-19-related pulmonary failure and the number of patients recovering from COVID-19 is growing. Here, we assess survival and recovery 6 months after ECMO for COVID-19. From April 2020 to September 2021, n = 60 (60.5 [51.0–65.0] years, 23.3% female) were treated with venovenous/venoarterial ECMO for COVID-19. 41.7% were weaned off ECMO, survival-to-discharge was 40.0% (n = 24). Age (63.0 [60.0–66.8] vs. 55.0 [43.8–60.0] years, p < 0.001), vasoactive support (97.2% vs. 75.0%, p = 0.013), and pre-ECMO SOFA scores (13.0 [12.0–14.8] vs. 12.0 [10.0–13.8] p = 0.036) correlated with nonsurvival. All patients aged >65 years, with histories of neoplasia, immunocompromise, chronic renal failure, or frailty died. After 6 months, 20 were alive (6-month survival 33.3%, survival conditioned on survival-to-discharge 83.3%), with follow-up in 19. 57.9% showed no relevant, 26.3% moderate, 15.8% severe deficits. Cardiopulmonary status was satisfactory (mMRC level: 84.2% ≤2). 73.7% were independent in daily life. Cognitive impairments were frequent (52.6%). 26.3% showed moderate depression, 15.8% posttraumatic stress disorder. Social and work life were considerably affected. Extracorporeal membrane oxygenation thus can serve as salvage therapy in COVID-19, but advanced age, immunocompromise, histories of neoplasia, and frailty must be considered as relative contraindications. Age, vasoactive support, and SOFA scores assist discriminating in daily practice. Deficits after 6 months are substantial, and efforts need to focus on long-term recovery.
Chronic pain in haemophilia: assessment and analgesic treatment
Authors: De la Corte-Rodriguez Hortensia , Rodriguez-Merchan E. Carlos
Published: May 2023

People with haemophilia tend to experience pain from an early age because of venipuncture and hemarthrosis. If pain is not properly managed, it can become chronic and bedevil patients throughout their lives. Therapies are currently available that have been shown to effectively treat the different types of pain and their causes. Patients with haemophilia tend to experience either nociceptive or mixed pain. Identification of the cause of pain by means of imaging techniques, and understanding the characteristics, location and intensity of the pain, are essential for a more targeted therapeutic approach. Current data reveal that the most effective measures are administration of haematological and analgesic medication, intraarticular injections, and physical exercise. However, multimodal strategies such as lifestyle changes, physical modalities, psychological support and orthopaedic surgery can also prove of use. This article will look at the most effective analgesic measures used as a part of conservative clinical treatment. Collaborative studies are needed to better understand the nature of pain in the context of haemophilia.
Foundations of hemophilia and epidemiology
Authors: Quintana Paris Laura
Published: May 2023

Hemophilia, a congenital coagulopathy characterized by a deficiency in coagulation factor VIII (hemophilia A) or factor IX (hemophilia B), results in a tendency of bleeding proportional to the lacking factor. Most bleeds in patients with hemophilia occur in their joints and muscles, and because of these bleeding episodes, patients may end up developing musculoskeletal alterations resulting from hemophilic arthropathy, even receiving hemostatic treatment. The third edition of the World Federation of Hemophilia's Guidelines for the Management of Hemophilia defines 12 principles that encompass all the different types of multidisciplinary care required by people with hemophilia, one of these being clinical and epidemiological research. The expected number of patients with hemophilia across the world has been estimated at 1125 000, most of them undiagnosed, and the total number of patients with severe hemophilia at 418 000 males. Data available from medium and high-income countries show that the prevalence at birth (incidence) and the prevalence of hemophilia differ, which means that patients with hemophilia are at a disadvantage in terms of life expectancy as compared with the general population. In medium-to-high-income countries, the life expectancy disadvantage of patients with hemophilia A and B as compared with the rest of the population is 30% and 24%, respectively. This life expectancy disadvantage is much greater in countries with more limited access to treatments for hemophilia.
Trends in patient’s use of sexual health services during COVID-19 in a network of STD clinics, STD Surveillance Network, 2019- 2021
Authors: Llata Eloisa , Schumacher Christina , Grigorov Irina , Danforth Brandi , Pathela Preeti , Asbel Lenore , Nguyen Trang Quyen , Berzkalns Anna , Kreisel Kristen M.
Published: May 2023

Background

The initial years of the COVID-19 pandemic disrupted sexual healthcare clinic’s services. We describe use patterns by patient characteristics, and the use of telehealth (TH) services among a network of sexually transmitted disease (STD) clinics.

Methods

Data were collected using a survey to assess the impact of COVID-19 from March – December 2020 among seven jurisdictions who contribute STD visit-level data as part of the STD Surveillance Network. As a complement to the survey, retrospective data from January 2019 – December 2021 from these seven STD clinics in the same seven jurisdictions were examined for monthly utilization trends by overall visits, patient characteristics, and TH visits.

Results

Survey results indicated seven clinics prioritized patients for in-person visits and four jurisdictions reported urgent care centers were the most common referral location. In April 2020 (relative to April 2019) clinic visits and unique patients decreased by 68.0% and 75.8%, respectively. TH were documented in four clinics, beginning in March 2020, peaking in December 2020, and tapering until December 2021. We observed the number of clinic visits (-12.2%) and unique patients presenting for care (-27.2%)in December 2021 had yet to return to levels to that seen in December 2019.

Conclusion

STD clinics showed fragility and resiliency in their adjustment to the pandemic; allowing for the continuation of services. Overall patient census has been slow to return to pre-pandemic levels, and many patients may still not be seeking timely care. This could result in missed opportunities to screen and treat STIs and increasing the possibility of harmful sequelae.
Examining the Patterns of Mpox Vaccine Uptake in a Vulnerable Population
Authors: Zucker Roy , Wolff-Sagy Yael , Ramot Noga , Raviv Yuval , Lavie Gil , Netzer Doron , Hammerman Ariel , Arbel Ronen
Published: May 2023

Background

The current Mpox outbreak presents unique vaccination challenges in vulnerable populations. Understanding factors associated with vaccine uptake in vulnerable populations is required for a successful vaccination campaign.

Methods

This population-based cohort study was conducted in Clalit Health Services (CHS) and included all individuals eligible for the MVA vaccine. Cox proportional hazards models were used to assess the characteristics associated with uptake of the first vaccine dose.

Results

Attendance to a primary healthcare clinic in the Tel Aviv district, repeated STI screening, and the recent purchase of HIV-PrEP or PDE5 inhibitors were associated with higher vaccine adherence, while previous non-adherence with recommended vaccines, low sociodemographic status, and history of HIV were associated with lower adherence.

Conclusions

These findings highlight the need for proactive patient and healthcare provider-oriented educational campaigns to curb vaccine hesitancy, and may help direct resources toward underserved populations, hence increasing equality in vaccine enrollment.
Complications of Long-Acting Reversible Contraceptive Modalities
Authors: Irgens-Moller Nicole , Baum Carl R.
Published: May 2023

Long-acting reversible contraception has risen in popularity in recent decades and is becoming one of the more common modalities of contraception in the United States, with a growing adolescent population among its users. The 2 modalities of long-acting reversible contraception—intrauterine devices and subcutaneous hormonal implants/etonogestrel implants (referred to as Nexplanon in the US)—are beneficial for their excellent effectiveness, ease of use, and safety profile. This article reviews the pharmacology of these modalities, common complications and their presentations, and the initial evaluation and management in the pediatric emergency department setting. Where applicable, attention will be paid to problems unique to the adolescent population.