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Infectious laryngotracheitis (ILT) is a respiratory disease affecting chickens worldwide. Unlike many countries, Switzerland does not vaccinate against ILT. This study analysed ILT samples from 21 natural outbreaks in Switzerland using restriction fragment length polymorphism (RFLP) and multiple gene sequencing. Chicken embryo origin (CEO) and tissue culture origin (TCO) vaccine strains were included as references. Both vaccine strains were distinguishable, and 14 out of 21 samples resembled the CEO vaccine. Additionally, four distinct non-vaccine-like groups were identified. Sequencing of three genes from selected Swiss samples and those from neighbouring countries revealed four phylogenetic clades. Notably, four Swiss field strains formed two unique clades, not closely related to vaccine strains or ILTV from neighbouring countries. Overall, RFLP results were supported by sequencing data. This study demonstrates the presence of both vaccine-like and wild-type ILT viruses in Switzerland, where vaccination is de facto prohibited.

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BACKGROUND: The Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) identified increased serotype 4 invasive pneumococcal disease (IPD), particularly among adults experiencing homelessness (AEH). METHODS: We quantified IPD cases during 2016-2022. Employing genomic-based characterization of IPD isolates, we identified serotype-switch variants. Recombinational analyses were used to identify the genetic donor and recipient strains that generated a serotype 4 progeny strain. We performed phylogenetic analyses of the serotype 4 progeny and serotype 12F genetic recipient to determine genetic distances. RESULTS: We identified 30 inter-related (0-21 nucleotide differences) IPD isolates recovered during 2022-2023, corresponding to a serotype 4 capsular-switch variant. This strain arose through a multi-fragment recombination event between serotype 4/ST10172 and serotype 12F/ST220 parental strains. Twenty-five of the 30 cases occurred within Oregon. Of 29 cases with known residence status, 16 occurred in AEH. Variant emergence coincided with a 2.6-fold increase (57 to 148) of cases caused by the serotype 4/ST10172 donor lineage in 2022 compared to 2019 and its first appearance in Oregon. Most serotypes showed sequential increases of AEH IPD/all IPD ratios during 2016-2022 (for all serotypes combined, 247/2198, 11.2% during 2022 compared to 405/5317, 7.6% for 2018-2019, p<0.001). Serotypes 4 and 12F each caused more IPD than any other serotypes in AEH during 2020-2022 (207 combined reported cases primarily in 4 western states accounting for 38% of IPD in AEH). CONCLUSION: Expansion and increased transmission of serotypes 4 and 12F among adults potentially led to recent genesis of an impactful hybrid "serotype-switch" variant.

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Owing to the increasing use of computers, computer-aided drug design (CADD) has become an essential component of drug discovery research. In structure-based drug design (SBDD), including inhibitor design and in silico screening of drug target molecules, concordance with wet experimental data is important to provide insights on unique perspectives derived from calculations. Fragment molecular orbital (FMO) method is a quantum chemical method that facilitates precise energy calculations. Fragmentation method makes it possible to apply the quantum chemical method to biological macromolecules for energy calculation based on the electron behavior. Furthermore, interaction energies calculated on a residue-by-residue basis via fragmentation aid in the analysis of interactions between the target and ligand molecule residues and molecular design. In this review, we outline the recent developments in SBDD and FMO methods and highlight the prospects of developing machine learning approaches for large computational data using the FMO method.

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The use of computational methods in drug discovery research has increased substantially in recent years. Computational chemistry techniques, such as quantum chemical calculations and molecular dynamics simulations, continue to be widely used. In this review, we focused on drug discovery-related studies that employ fragment molecular orbital methods. Furthermore, we focused on inhibitor discovery, protein-protein interaction analysis, including antigen-antibody interaction analysis, and integration with molecular dynamics simulations.

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Microplastics (MPs) are particles between 1 µm and 5 mm in size, originating mainly from poor solid waste and effluent management, that can reach water bodies from various sources. In freshwater environments, the occurrence, distribution, and characterization of this new class of pollutants are still little explored, especially in Brazil. The aim of this study was to assess the occurrence of MPs, as well as the presence and concentration of polychlorinated biphenyls (PCBs) sorbed to these particles in the surface waters of the Tietê River - SP. Surface water samples were collected in duplicate during the dry and wet seasons. The identification and characterization of the MPs was carried out through visual inspection and the chemical identity of the particles was verified using Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR). For the analysis of PCBs adsorbed to the MPs, the sample extracts were analyzed by gas chromatography coupled with mass spectrometry (GC-MS). The MPs were found in concentrations ranging from 6.67 to 1530 particles m-3, with a predominance of the polymers polyethylene (PE, with 58.17 %) and polypropylene (PP, with 23.53 %). The main morphological categories identified were fragments (56.63 %), fibers (28.42 %), and transparent films (13.06 %). Higher abundances of PCBs were observed in the lower size range, between 0.106 and 0.35 mm. The total concentrations of PCBs in MPs ranged from 20.53 to 133.12 ng g-1. The results obtained here are relevant for understanding the dynamics and level of contamination of MPs and organic pollutants sorbed to these particles in the Tietê River, as well as helping with mitigation measures for the restoration and preservation of this ecosystem.

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Background: Collaborative documentation (CD) is a behavioral health practice involving shared writing of clinic visit notes by providers and consumers. Despite widespread dissemination of CD, research on its effectiveness or impact on person-centered care (PCC) has been limited. Principles of PCC planning, a recovery-based approach to service planning that operationalizes PCC, can inform the measurement of person-centeredness within clinical documentation. Objective: This study aims to use the clinical informatics approach of natural language processing (NLP) to examine the impact of CD on person-centeredness in clinic visit notes. Using a dictionary-based approach, this study conducts a textual analysis of clinic notes from a community mental health center before and after staff were trained in CD. Methods: This study used visit notes (n=1981) from 10 providers in a community mental health center 6 months before and after training in CD. LIWC-22 was used to assess all notes using the Linguistic Inquiry and Word Count (LIWC) dictionary, which categorizes over 5000 linguistic and psychological words. Twelve LIWC categories were selected and mapped onto PCC planning principles through the consensus of 3 domain experts. The LIWC-22 contextualizer was used to extract sentence fragments from notes corresponding to LIWC categories. Then, fixed-effects modeling was used to identify differences in notes before and after CD training while accounting for nesting within the provider. Results: Sentence fragments identified by the contextualizing process illustrated how visit notes demonstrated PCC. The fixed effects analysis found a significant positive shift toward person-centeredness; this was observed in 6 of the selected LIWC categories post CD. Specifically, there was a notable increase in words associated with achievement (ß=.774, P<.001), power (ß=.831, P<.001), money (ß=.204, P<.001), physical health (ß=.427, P=.03), while leisure words decreased (ß=-.166, P=.002). Conclusions: By using a dictionary-based approach, the study identified how CD might influence the integration of PCC principles within clinical notes. Although the results were mixed, the findings highlight the potential effectiveness of CD in enhancing person-centeredness in clinic notes. By leveraging NLP techniques, this research illuminated the value of narrative clinical notes in assessing the quality of care in behavioral health contexts. These findings underscore the promise of NLP for quality assurance in health care settings and emphasize the need for refining algorithms to more accurately measure PCC.

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BACKGROUND: Currently, most HIV drug resistance PCR assays amplify the protease-reverse transcriptase (PR-RT) fragment separately from the integrase (IN) fragment. The aim of this study was to develop a multiplex PCR assay that simultaneously amplifies PR-RT and IN fragments for HIV-1 drug-resistance testing. METHODS: The in-house multiplex PCR assay was evaluated on extracted total nucleic acids obtained from the National Health Laboratory Service (NHLS) and Lancet laboratories. Sanger sequencing was performed on amplicons, and HIV-1 drug-resistance mutations (DRMs) were assessed using HIV Stanford drug resistance database. RESULTS: This study tested 59 patient samples with known HIV-1 viral load and DRM results; 41 from Lancet and 18 from NHLS. In-house multiplex PCR assay detected one or both fragments in most samples but had higher sensitivity for detection of IN fragment (93.2%) compared to PR-RT fragment (83.1%). There was 100% concordance between Lancet assay versus in-house assay sequence data for IN DRMs, but lower concordance with PR-RT (87.0%). The in-house multiplex PCR assay's precision and reproducibility analysis showed ≥99.9% sequence similarity and yielded similar DRM results for both PR-RT and IN fragments. CONCLUSIONS: The in-house multiplex PCR assay demonstrated satisfactory performance and higher sensitivity for IN fragment amplification. This could be a cost-effective method for HIV-1 drug resistance testing as both PR-RT and IN fragments are successfully amplified in one reaction in most samples.

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The development of liquid biopsy as a minimally invasive technique for tumor profiling has created a need for efficient biomarker extraction systems from body fluids. The analysis of circulating cell-free DNA (cfDNA) is especially promising, but the low amounts and high fragmentation of cfDNA found in plasma pose challenges to its isolation. While the potential of aqueous two-phase systems (ATPS) for the extraction and purification of various biomolecules has already been successfully established, there is limited literature on the applicability of these findings to short cfDNA-like fragments. This study presents the partitioning behavior of a 160 bp DNA fragment in polyethylene glycol (PEG)/salt ATPS at pH 7.4. The effect of PEG molecular weight, tie-line length, neutral salt additives, and phase volume ratio is evaluated to maximize DNA recovery. Selected ATPS containing a synthetic plasma solution spiked with human serum albumin and immunoglobulin G are tested to determine the separation of DNA fragments from the main plasma protein fraction. By adding 1.5% (w/w) NaCl to a 17.7% (w/w) PEG 400/17.3% (w/w) phosphate ATPS, 88% DNA recovery was achieved in the salt-rich bottom phase while over 99% of the protein was removed.

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BACKGROUND: The purpose of the study is to examine if prolonged thromboprophylaxis decreases the risk of thrombosis after intended curative surgery for oesophageal cancer. Study results are expected to inform a guideline for thromboprophylaxis after oesophageal cancer surgery. The perspective is to reduce morbidity and mortality in this critically ill patient group. Thrombosis is the second-most common cause of cancer death after the cancer itself. The risk of thrombosis depends on the cancer type, and upper gastrointestinal cancers are considered high risk. This risk is further increased when patients undergo surgery. However, only few studies have investigated the peri- and postoperative coagulation profile in oesophageal cancer patients. Due to this lack of knowledge, prophylaxis is currently restricted to 5000 IU (international units) low-molecular weight heparin daily from surgery until discharge from hospital (approximately 10 days), whereas patients with gastric cancer receive 30 days of treatment. The present study examines whether a 30-day treatment is superior and safe, compared with the current standard treatment. METHODS: The study is a randomised controlled trial. Inclusion is ongoing, and we aim to include 100 patients. Blood samples are drawn before and after surgery, and the coagulation is extensively examined. The primary endpoint is the difference in plasma levels of prothrombin fragment 1 + 2 (F1 + 2) 30 days after surgery between the intervention and the standard group. Furthermore, patients are examined with ultrasound to screen for asymptomatic venous thrombotic events (VTE). Secondary endpoints are incidence of bleeding, symptomatic and asymptomatic VTE and mortality 30 days 1 one year after surgery. DISCUSSION: The study will provide valuable information on the perioperative coagulation profile and VTE risk of oesophageal cancer patients. The study seeks to aid in optimising the postoperative thromboprophylaxis, and the perspective is to reduce morbidity and mortality in this at-risk patient population. TRIALS REGISTRATION: The trial was prospectively registered at the EU Clinical Trials Register with ID 2021-001335-24 on 30 June 2021 and at ClinicalTrials.gov with study identifier NCT05067153.

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Background: Interleukin-10 (IL-10) is an anti-inflammatory cytokine whose levels are elevated in patients with severe COVID-19. IL-10 polymorphisms may play a role in increasing IL-10 levels and the severity of COVID-19. This study aimed to investigate the relationship between IL-10 single nucleotide polymorphisms (SNPs) (rs1800896 [-1082 C < T], rs1800871 [-819 A > G], and rs1800872 [-592 T > G]) and the severity of COVID-19 in patients from Kermanshah Province, Iran. Methods: A total of 150 patients with mild COVID-19 (84 men and 66 women aged 40.1 ± 12.44 years) and 143 patients with severe COVID-19 (76 men and 67 women aged 61.04 ± 15.65 years) participated in this study. Blood samples were collected from the patients, DNA was extracted, and the genotype of each SNPs was determined using the polymerase chain reaction-restriction fragment length polymorphism method. Result: The results of this study did not show a significant relationship between the genotypes of the three studied SNPs and the severity of COVID-19 (p > 0.05). Conclusion: According to our findings, these SNPs were not associated with COVID-19 severity in patients in Kermanshah.

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Chronic obstructive pulmonary disease (COPD) is the most prevalent lung disease, and macrophages play a central role in the inflammatory response in COPD. We here report a comprehensive characterization of circulating short non-coding RNAs (sncRNAs) in plasma from patients with COPD. While circulating sncRNAs are increasingly recognized for their regulatory roles and biomarker potential in various diseases, the conventional RNA sequencing (RNA-seq) method cannot fully capture these circulating sncRNAs due to their heterogeneous terminal structures. By pre-treating the plasma RNAs with T4 polynucleotide kinase, which converts all RNAs to those with RNA-seq susceptible ends (5'-phosphate and 3'-hydroxyl), we comprehensively sequenced a wide variety of non-microRNA sncRNAs, such as 5'-tRNA halves containing a 2',3'-cyclic phosphate. We discovered a remarkable accumulation of the 5'-half derived from tRNAValCAC in plasma from COPD patients, whereas the 5'-tRNAGlyGCC half is predominant in healthy donors. Further, the 5'-tRNAValCAC half activates human macrophages via Toll-like receptor 7 and induces cytokine production. Additionally, we identified circulating rRNA-derived fragments that were upregulated in COPD patients and demonstrated their ability to induce cytokine production in macrophages. Our findings provide evidence of circulating, immune-active sncRNAs in patients with COPD, suggesting that they serve as inflammatory mediators in the pathogenesis of COPD.

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Short-range MEMS-based (Micro Electronical Mechanical System) LiDAR provides precise point cloud datasets for rock fragment surfaces. However, there is more vibrational noise in MEMS-based LiDAR signals, which cannot guarantee that the reconstructed point cloud data are not distorted with a high compression ratio. Many studies have illustrated that wavelet-based clustered compressive sensing can improve reconstruction precision. The k-means clustering algorithm can be conveniently employed to obtain clusters; however, estimating a meaningful k value (i.e., the number of clusters) is challenging. An excessive quantity of clusters is not necessary for dense point clouds, as this leads to elevated consumption of memory and CPU resources. For sparser point clouds, fewer clusters lead to more distortions, while excessive clusters lead to more voids in reconstructed point clouds. This study proposes a local clustering method to determine a number of clusters closer to the actual number based on GMM (Gaussian Mixture Model) observation distances and density peaks. Experimental results illustrate that the estimated number of clusters is closer to the actual number in four datasets from the KEEL public repository. In point cloud compression and recovery experiments, our proposed approach compresses and recovers the Bunny and Armadillo datasets in the Stanford 3D repository; the experimental results illustrate that our proposed approach improves reconstructed point clouds' geometry and curvature similarity. Furthermore, the geometric similarity increases to 0.9 above in our complete rock fragment surface datasets after selecting a better wavelet basis for each dimension of MEMS-based LiDAR signals. In both experiments, the sparsity of signals was 0.8 and the sampling ratio was 0.4. Finally, a rock outcrop point cloud data experiment is utilized to verify that the proposed approach is applicable for large-scale research objects. All of our experiments illustrate that the proposed adaptive clustered compressive sensing approach can better reconstruct MEMS-based LiDAR point clouds with a lower sampling ratio.

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Agrin is essential for neuromuscular junction (NMJ) formation and maintenance. The C-terminal agrin fragment (CAF), generated by neurotrypsin-mediated cleavage of agrin, has been gaining attention as a potential biomarker for sarcopenia. We investigated serum CAF levels in myasthenia gravis (MG), a NMJ disorder. Compared to healthy controls, serum CAF levels were significantly elevated in acetylcholine receptor antibody-positive MG (AChR-MG) patients, but not in muscle-specific kinase antibody-positive MG patients. In AChR-MG, baseline and post-treatment CAF levels inversely correlated with post-treatment MG activities of daily living scores, suggesting that elevated CAF levels may reflect protective mechanisms against AChR-MG pathogenesis, such as improved NMJ regeneration.

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Background: Tumor markers such as serum carcinoembryonic antigen (CEA) and cytokeratin fragment 19 (CYFRA 21-1) are utilized for assessing the effectiveness of chemotherapy in non-small cell lung cancer (NSCLC) patients. Yet, it remains uncertain whether these markers can reliably forecast responses to combined chemoimmunotherapy. Our study aimed to examine the significance and effectiveness of these markers in predicting responses among NSCLC patients undergoing combined chemoimmunotherapy. Methods: This two-part observational study involved patients with NSCLC who were treated with combined chemoimmunotherapy in Japanese hospitals. An initial retrospective study of these patients, with serum CEA and CYFRA 21-1 as prognostic factors for combined chemoimmunotherapy outcomes, served as a discovery cohort. Patients in a subsequent prospective study served as a validation cohort, where we assessed the prognostic accuracy of CEA and CYFRA 21-1 cut-off points determined by the discovery cohort. Results: In total, 121 patients treated with combined chemoimmunotherapy were included, with 44 and 77 patients in the discovery and validation cohorts, respectively. Serum CYFRA 21-1 levels >3.0 ng/mL were significantly associated with progression-free survival (PFS) in both the discovery and validation cohorts (P=0.01, P=0.04, respectively). PFS did not differ significantly by CEA levels (P=0.21). Conclusions: After combined chemoimmunotherapy treatment, serum CYFRA 21-1 stands out as a potentially valuable biomarker for predicting the prognosis of NSCLC.

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BACKGROUND: Jasminum sambac, a widely recognized ornamental plant prized for its aromatic blossoms, exhibits three flora phenotypes: single-petal ("SP"), double-petal ("DP"), and multi-petal ("MP"). The lack of detailed characterization and comparison of J. sambac mitochondrial genomes (mitogenomes) hinders the exploration of the genetic and structural diversity underlying the varying floral phenotypes in jasmine accessions. RESULTS: Here, we de novo assembled three mitogenomes of typical phenotypes of J. sambac, "SP", "DP", and "MP-hutou" ("HT"), with PacBio reads and the "HT" chloroplast (cp) genome with Illumina reads, and verified them with read mapping and fluorescence in situ hybridization (FISH). The three mitogenomes present divergent sub-genomic conformations, with two, two, and four autonomous circular chromosomes ranging in size from 35.7 kb to 405.3 kb. Each mitogenome contained 58 unique genes. Ribosome binding sites with conserved AAGAAx/AxAAAG motifs were detected upstream of uncanonical start codons TTG, CTG and GTG. The three mitogenomes were similar in genomic content but divergent in structure. The structural variations were mainly attributed to recombination mediated by a large (~ 5 kb) forward repeat pair and several short repeats. The three jasmine cp. genomes showed a well-conserved structure, apart from a 19.9 kb inversion in "HT". We identified a 14.3 kb "HT"-specific insertion on Chr7 of the "HT" nuclear genome, consisting of two 7 kb chloroplast-derived fragments with two intact ndhH and rps15 genes, further validated by polymerase chain reaction (PCR). The well-resolved phylogeny suggests faster mitogenome evolution in J. sambac compared to other Oleaceae species and outlines the mitogenome evolutionary trajectories within Lamiales. All evidence supports that "DP" and "HT" evolved from "SP", with "HT" being the most recent derivative of "DP". CONCLUSION: The comprehensive characterization of jasmine organelle genomes has added to our knowledge of the structural diversity and evolutionary trajectories behind varying jasmine traits, paving the way for in-depth exploration of mechanisms and targeted genetic research.

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Purpose: Multiple loose bodies (LBs) are often found in patients with varus ankle osteoarthritis (OA). This study aimed to investigate the characteristics of extra-articular posterior ankle LBs in patients with varus ankle OA. We also sought to determine whether there were variations in the characteristics of LBs according to the degree of ankle OA. Methods: We retrospectively reviewed 50 patients who had appeared posterior extraarticular LBs on preoperative ankle imaging among the patients who underwent operative treatment for varus ankle OA from March 2011 to February 2023. We categorized the entire patient cohort into four groups according to the degree of ankle arthritis (Takakura stage II, IIIA, IIIB, and IV). Size, number, and location of LBs were evaluated using preoperative computed tomography and magnetic resonance imaging. Results: 142 LBs were identified (mean size: 11.5 mm); 76.8% were located within the flexor hallucis longus (FHL) tendon sheath, 20.4% in the posterior recess, and 2.8% in the flexor digitorum longus tendon sheath. Average LB size was significantly larger in Takakura stage IIIB and IV patients (p < .05), and the LB number was significantly lower in stage II patients (p = .013). Conclusion: Extra-articular posterior LBs in varus ankle OA are predominantly located within the FHL tendon sheath and were larger in Takakura stages IIIB and IV patients.Level of Evidence: Level III. Retrospective comparative study.

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We recently introduced calix[n]naphth[m]arenes as a novel class of deep-cavity hybrid macrocycles constituted by phenol (n) and naphthalene (m) units. In this study, we report the synthesis, conformational analysis, spectroscopic properties, and solid-state structures of calix[4]naphth[4]arene (C4N4) and its permethylated analog (C4N4-Me), thereby expanding the calix[n]naphth[m]arene family. C4N4 was synthesized through a 2 + 2 fragment coupling macrocyclization under acidic conditions, where the solvent played a crucial role in selectively forming the C4N4 derivative. The X-ray structure of C4N4 reveals a chair-like 1,2,3,4-alternate conformation characterized by two opposing 3/4-cone moieties stabilized by intramolecular hydrogen bonds. In contrast, the X-ray structure of C4N4-Me exhibits a 1,3,5,7-alternate conformation.

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Accurate assessment of fragment abundance within a genome is crucial in clinical genomics applications such as the analysis of copy number variation (CNV). However, this task is often hindered by biased coverage in regions with varying guanine-cytosine (GC) content. These biases are particularly exacerbated in hybridization capture sequencing due to GC effects on probe hybridization and polymerase chain reaction (PCR) amplification efficiency. Such GC content-associated variations can exert a negative impact on the fidelity of CNV calling within hybridization capture panels. In this report, we present panelGC, a novel metric, to quantify and monitor GC biases in hybridization capture sequencing data. We establish the efficacy of panelGC, demonstrating its proficiency in identifying and flagging potential procedural anomalies, even in situations where instrument and experimental monitoring data may not be readily accessible. Validation using real-world datasets demonstrates that panelGC enhances the quality control and reliability of hybridization capture panel sequencing.

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Perforation of the skin by fragment impact is a key determinant of the severity of an injury and incapacitation during modern asymmetric warfare. Computational models validated against experimental data are thus desired for simulating the responses of a skin simulant against fragment impact. Toward this end, experiments and concurrent computational modeling were used to investigate the dynamic responses of the skin simulant against fragment impact. Fragment simulating projectiles (FSPs) of masses 1.10 g and 2.79 g were considered herein, and the responses of the skin simulant were investigated in terms of the threshold velocity, energy density, peak displacement, and failure mechanisms. The results illustrate numerous salient aspects. The skin simulant failure involved cavity shearing followed by elastic hole enlargement, and these results were sensitive to the strain rate. The best agreement between the simulated and experimental results was achieved when the input stress-strain curves to the simulation were based on the full spectrum of strain rates. When a single stress-strain curve corresponding to a specific strain rate was used as the input, the threshold velocity and peak displacement of the skin simulant were either underpredicted or overpredicted depending on the strain rate considered. The threshold velocity was also sensitive to the input failure strain; here, the best agreement was obtained when the failure strain was based on the theoretical limiting strain. When the FSP materials were changed to plastics, the threshold velocities increased by up to 33%; however, the energy densities and generated stresses exceeded the contusion and laceration thresholds of the skin.

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Acute appendicitis is an ordinary surgical emergency, typically attributed to luminal obstruction by fecaliths or lymphoid hyperplasia. However, ingested foreign bodies as an etiology are rare but increasingly recognized, particularly in pediatric patients. We present the case of a 9-year-old male patient who presented to the emergency department with symptoms consistent with acute appendicitis. Further investigation revealed the presence of a bone fragment within the appendix, leading to acute inflammation. Foreign body ingestion should be considered in pediatric patients with acute appendicitis. This case report underscores the importance of comprehensive clinical evaluation and appropriate diagnostic imaging modalities in guiding optimal treatment strategies.