Investigating the uses of machine learning algorithms to inform risk factor analyses: The example of avian infectious bronchitis virus (IBV) in broiler chickens.

Infectious bronchitis virus (IBV) is a contagious coronavirus causing respiratory and urogenital disease in chickens and is responsible for significant economic losses for both the broiler and table egg layer industries. Despite IBV being regularly monitored using standard epidemiologic surveillance practices, knowledge and evidence of risk factors associated with IBV transmission remain limited. The study objective was to compare risk factor modeling outcomes between a traditional stepwise variable selection approach and a machine learning-based random forest Boruta algorithm using routinely collected IBV antibody titer data from broiler flocks. IBV antibody sampling events (n = 1111) from 166 broiler sites between 2016 and 2021 were accessed. Ninety-two geospatial-related and poultry-density variables were obtained using a geographic information system and data sets from publicly available sources. Seventeen and 27 candidate variables were screened to potentially have an association with elevated IBV antibody titers according to the manual selection and machine learning algorithm, respectively. Selected variables from both methods were further investigated by construction of multivariable generalized mixed logistic regression models. Six variables were shortlisted by both screening methods, which included year, distance to urban areas, main roads, landcover, density of layer sites and year, however, final models for both approaches only shared year as an important predictor. Despite limited significance of clinical outcomes, this work showcases the potential of a novel explorative modeling approach in combination with often unutilized resources such as publicly available geospatial data, surveillance health data and machine learning as potential supplementary tools to investigate risk factors related to infectious diseases.

Single-Mode Laser in the Telecom Range by Deterministic Amplification of the Topological Interface Mode.

Photonic integrated circuits are paving the way for novel on-chip functionalities with diverse applications in communication, computing, and beyond. The integration of on-chip light sources, especially single-mode lasers, is crucial for advancing those photonic chips to their full potential. Recently, novel concepts involving topological designs introduced a variety of options for tuning device properties, such as the desired single-mode emission. Here, we introduce a novel cavity design that allows amplification of the topological interface mode by deterministic placement of gain material within a topological lattice. The proposed design is experimentally implemented by a selective epitaxy process to achieve closely spaced Si and InGaAs nanorods embedded within the same layer. This results in the first demonstration of a single-mode laser in the telecom band using the concept of amplified topological modes without introducing artificial losses.

Phase of Topological Lattice with Leaky Guided Mode Resonance.

Topological nature in different areas of physics and electronics has often been characterized and controlled through topological invariants depending on the global properties of the material. The validity of bulk-edge correspondence and symmetry-related topological invariants has been extended to non-Hermitian systems. Correspondingly, the value of geometric phases, such as the Pancharatnam-Berry or Zak phases, under the adiabatic quantum deformation process in the presence of non-Hermitian conditions, are now of significant interest. Here, we explicitly calculate the Zak phases of one-dimensional topological nanobeams that sustain guided-mode resonances, which lead to energy leakage to a continuum state. The retrieved Zak phases show as zero for trivial and as π for nontrivial photonic crystals, respectively, which ensures bulk-edge correspondence is still valid for certain non-Hermitian conditions.

Efficacy of inactivated and RNA particle vaccines against a North American Clade 2.3.4.4b H5 highly pathogenic avian influenza virus in chickens.

Highly pathogenic avian influenza virus (HPAIV) has caused widespread outbreaks in poultry in the Americas. Because of the duration and extent of these outbreaks, vaccine use may be an additional tool to limit virus spread. Three vaccines were evaluated for efficacy in chickens against a current North American clade 2.3.4.4b H5 HPAIV isolate, A/turkey/Indiana/3703-003/2022 H5N1. The vaccines included: 1) a commercial inactivated reverse genetics (rg) generated H5N1 product with a clade 2.3.4.4c H5 hemagglutinin (HA) (rgH5N1); 2) a commercial alphavirus RNA particle (RP) vaccine with the TK/IN/22 HA; and 3) an in-house inactivated rg produced vaccine with the TK/IN/22 HA and a North American lineage N9 neuraminidase (NA) (SEP-22-N9). Both inactivated vaccines were produced with HA genes that were modified to be low pathogenic and with the remaining genes from the PR8 influenza strain. All vaccines provided 100% protection against mortality and morbidity and all vaccines reduced virus shed by the oropharyngeal and cloacal routes significantly compared to sham vaccinates. However, differences were observed among the vaccines in quantities of virus shed at two- and four-days post challenge (DPC). To determine if infected birds could be identified after vaccination to aid surveillance programs, serum was collected from the RP and SEP-22-N9 vaccine groups at 7, 10, and 14 DPC to detect antibody to the NA and nucleoprotein (NP) of the challenge virus by enzyme linked lectin assay (ELLA) and ELISA. As early as 7DPC ELLA detected antibody in sera from 100% of the chickens in the RP vaccinated group and 70% of the chickens in the SEP-22-N9 vaccinated group. Antibody to the NP was detected by commercial ELISA in more than 50% of the birds in the RP vaccinated group at each time point.

Diversity and Complexity of Internally Deleted Viral Genomes in Influenza A Virus Subpopulations with Enhanced Interferon-Inducing Phenotypes.

Influenza A virus (IAV) populations harbor large subpopulations of defective-interfering particles characterized by internally deleted viral genomes. These internally deleted genomes have demonstrated the ability to suppress infectivity and boost innate immunity, rendering them promising for therapeutic and immunogenic applications. In this study, we aimed to investigate the diversity and complexity of the internally deleted IAV genomes within a panel of plaque-purified avian influenza viruses selected for their enhanced interferon-inducing phenotypes. Our findings unveiled that the abundance and diversity of internally deleted viral genomes were contingent upon the viral subculture and plaque purification processes. We observed a heightened occurrence of internally deleted genomes with distinct junctions in viral clones exhibiting enhanced interferon-inducing phenotypes, accompanied by additional truncation in the nonstructural 1 protein linker region (NS1Δ76-86). Computational analyses suggest the internally deleted IAV genomes can encode a broad range of carboxy-terminally truncated and intrinsically disordered proteins with variable lengths and amino acid composition. Further research is imperative to unravel the underlying mechanisms driving the increased diversity of internal deletions within the genomes of viral clones exhibiting enhanced interferon-inducing capacities and to explore their potential for modulating cellular processes and immunity.

Toll-like Receptor Ligands Enhance Vaccine Efficacy against a Virulent Newcastle Disease Virus Challenge in Chickens.

To enhance the efficacy of the current Newcastle disease vaccine, we have selected potential adjuvants that target well-characterized pattern recognition receptors: the toll-like receptors (TLRs). Imiquimod is a small-molecule activator of TLR7, which is a sensor of dsDNA. ODN-1826 is a mimetic of CpG DNA and ligates TLR21 (a chicken homologue of TLR9 in mammals). The activation of TLRs leads to antiviral responses, including the induction of type I interferons (IFNs). In this study, birds were vaccinated intranasally with a live LaSota strain with or without imiquimod or ODN-1826 (50 µg/bird). Two weeks after vaccination, the birds were challenged with a virulent Newcastle disease virus (chicken/CA/212676/2002). Both adjuvants (imiquimod or ODN-1826) induced higher and more uniform antibody titers among vaccinated birds compared with the live vaccine-alone group. In addition, adjuvanted vaccines demonstrated greater protective efficacy in terms of the reduction in virus-shedding titer and the number of birds shedding the challenge virus at 2 and 4 days post-challenge. A differential expression of antiviral and immune-related genes was observed among groups from tissues (Harderian gland, trachea, cecal tonsil, and spleen) collected 1 and 3 days after treatment. These results demonstrate the potential of TLR-targeted adjuvants as mucosal vaccine enhancers and warrant a further characterization of immune correlates and optimization for efficacy.

Plasma Enhanced Atomic Layer Deposition of Silicon Nitride for Two Different Aminosilane Precursors Using Very High Frequency (162 MHz) Plasma Source.

Plasma enhanced atomic layer deposition (PEALD) of silicon nitride (SiNx) using very high frequency (VHF, 162 MHz) plasma source was investigated at the process temperatures of 100, 200, and 300 °C. Two aminosilane precursors having different numbers of amino ligands, bis(tert-butylamino)silane (BTBAS) and di(sec-butylamino)silane (DSBAS), were used as Si precursors. A comparative study was also conducted to verify the effect of the number of amino ligands on the properties of SiNx film. At all process temperatures, DSBAS, having one amino ligand, performed better than BTBAS in various aspects. SiNx films deposited using DSBAS had lower surface roughness, higher film density, lower wet etch rate, improved electrical characteristics, and higher growth rate than those deposited using BTBAS. With the combination of a VHF plasma source and DSBAS with one amino ligand, the SiNx films grown at 300 °C exhibited low wet etch rates (≤2 nm/min) in a dilute HF solution (100:1 of deionized water:HF) as well as low C content below the XPS detection limit. Also, excellent step coverage close to 100% on high aspect ratio (30:1) trench structures was obtained by using VHF plasma, which could provide sufficient flux of plasma species inside the trenches in conjunction with DSBAS having fewer amino ligands than BTBAS.

Genome Sequencing and Characterization of an Avian Orthoavulavirus 1 VG/GA-like Isolate with a Unique Fusion Cleavage Site Motif.

A complete genome sequence of a VG/GA -like strain of avian orthoavulavirus 1 (AOAV-1) was identified by nontargeted next-generation sequencing of an oropharyngeal swab sample collected from a carcass of a 12-mo-old backyard chicken. The isolate has a fusion (F) protein cleavage site motif consistent with a low virulent AOAV-1, but it has a unique motif with phenylalanine at position 117 (112G-R-Q-G-R↓F117), which is typical for virulent AOAV-1 strains. The one nucleotide difference at the cleavage site compared to other low-virulence viruses made the isolate detectable by F-gene-specific real-time reverse transcription-PCR (rRT-PCR) developed as a diagnostic test to specifically detect virulent strains. The mean death time determined in eggs and intracerebral pathogenicity index determined in chickens classified the isolate as lentogenic. This is the first report of a lentogenic VG/GA-like virus with a phenylalanine residue at position 117 of the F protein cleavage site in the United States. In addition to concern for potential pathogenic shift of the virus through additional changes at the cleavage site, our finding warrants increased awareness of diagnosticians of potential false positive F-gene rRT-PCR tests.

Secuenciación y caracterización del genoma de un aislado similar a VG/GA del ortoavulavirus aviar 1 con un motivo único en el sitio de disociación del gene de fusión. Se identificó una secuencia genómica completa de una cepa similar a la cepa Villegas-Glisson/Universidad de Georgia (VG/GA) del ortoavulavirus aviar 1 (AOAV-1) mediante secuenciación no dirigida de nueva generación de una muestra de hisopo orofaríngeo recolectada de una gallina muerta de traspatio de 12 meses. El aislado tiene un motivo en el sitio de disociación de la proteína de fusión (F) consistente con un ortoavulavirus aviar de baja virulencia, pero tiene un motivo único con fenilalanina en la posición 117 (112G-R-Q-G-R↓F117), que es típico para cepas virulentas del AOAV-1. La diferencia de un nucleótido en el sitio de escisión en comparación con otros virus de baja virulencia hizo que el aislado fuera detectable mediante transcripción reversa y PCR en tiempo real en tiempo real específica del gene F (rtRT-PCR) desarrollada como una prueba de diagnóstico para detectar específicamente a las cepas virulentas. El tiempo medio de muerte determinado en huevos y el índice de patogenicidad intracerebral determinado en pollos clasificaron al aislado como lentogénico. Este es el primer informe en los Estados Unidos de un virus lentogénico similar a VG/GA con un residuo de fenilalanina en la posición 117 del sitio de disociación de la proteína F. Además de la preocupación por el posible cambio patogénico del virus a través de cambios adicionales en el sitio de disociación, nuestro contribuye con un mayor conocimiento por parte del personal de diagnóstico acerca de posibles falsos positivos en las pruebas rtRT-PCR del gene F.

TLR3 and MDA5 Knockout DF-1 cells Enhance Replication of Avian Orthoavulavirus 1.

Despite the essential role of innate immunity in defining the outcome of viral infections, the roles played by different components of the avian innate immune system are poorly delineated. Here, we investigated the potential implication of avian toll-like receptor (TLR) 3 (TLR3) and melanoma differentiation-associated (MDA) gene 5 (MDA5) receptors of double-stranded RNA (dsRNA) in induction of the interferon pathway and avian orthoavulavirus 1 (AOAV-1) replication in chicken-origin DF-1 fibroblast cells. TLR3 and MDA5 knockout (KO) DF-1 cells were generated using our avian-specific CRISPR/Cas9 system and stimulated with a synthetic dsRNA ligand polyinosinic:polycytidylic acid [poly(I:C)] or infected with AOAV-1 (previously known as Newcastle disease virus). Poly(I:C) treatment in cell culture media resulted in significant upregulation of interferon (IFN)α, IFNß, and Mx1 gene expression in wild type (WT) DF-1 cells but not in TLR3-MDA5 double KO cells. Interestingly, poly(I:C) treatment induced rapid cell degeneration in WT and MDA5 KO cells, but not in TLR3 knockout or TRL3-MDA5 double knockout (DKO) cells, directly linking poly(I:C)-induced cell degeneration to TLR3-mediated host response. The double knockout cells supported significantly higher replication of AOAV-1 virus than did the WT cells. However, no correlation between the level of virus replication and type I IFN response was observed. Our study suggests that innate immune response is host- and pathogen specific, and further investigation is needed to understand the relevance of dsRNA receptor-mediated immune responses in viral replication and pathogenesis in avian species.

Nota de investigación- En bloqueo de los genes TLR3 y MDA5 en las células DF-1 mejoran la replicación de Ortoavulavirus aviar 1. A pesar del papel esencial de la inmunidad innata en la definición del resultado de las infecciones virales, las funciones que desempeñan los diferentes componentes del sistema inmunitario innato aviar no están completamente definidas. En este estudio se investigó el posible papel del receptor aviar tipo toll (TLR) número 3 (TLR3) y los receptores de ARN de doble cadena (dsRNA del gene asociado a la diferenciación de melanoma (MDA) número 5 (MDA5) en la inducción de la vía del interferón y en la replicación del Ortoavulavirus 1 (AOAV-1) en células de fibroblastos DF-1 de origen en pollo. Las células DF-1 con los genes TLR3 y MDA5 bloqueado (KO) se generaron utilizando nuestro sistema CRISPR/Cas9 específico para aves y se estimularon con un ligando de dsRNA sintético poliinosínico: ácido policitidílico [poli(I:C)] o se infectaron con AOAV-1 (anteriormente conocido como el virus de la enfermedad de Newcastle). El tratamiento con poli(I:C) en medios de cultivo celular resultó en una regulación positiva significativa de la expresión génica de interferón (IFN)α, IFNß y Mx1 en células DF-1 de tipo silvestre (WT) pero no en células con doble bloqueo TLR3-MDA5 (DKO). Curiosamente, el tratamiento con poli(I:C) indujo una rápida degeneración celular en las células silvestres (WT) y las células con el gene MDA5 bloqueado, pero no en las células con bloqueo del gene TLR3 o con las células con doble bloqueo de TRL3-MDA5, lo que vincula directamente la degeneración celular inducida por poli(I:C) con la respuesta de la huésped mediada por TLR3. Las células con doble bloqueo soportaron una replicación significativamente mayor del Ortoavulavirus 1 que las células silvestres. Sin embargo, no se observó correlación entre el nivel de replicación del virus y la respuesta de IFN tipo I. Este estudio sugiere que la respuesta inmune innata es específica del huésped y del patógeno, y se necesita más investigación para comprender la relevancia de las respuestas inmunes mediadas por el receptor dsRNA en la replicación viral y en la patogénesis en las especies aviares.

Conformational changes in the human Cx43/GJA1 gap junction channel visualized using cryo-EM.

Connexin family proteins assemble into hexameric hemichannels in the cell membrane. The hemichannels dock together between two adjacent membranes to form gap junction intercellular channels (GJIChs). We report the cryo-electron microscopy structures of Cx43 GJICh, revealing the dynamic equilibrium state of various channel conformations in detergents and lipid nanodiscs. We identify three different N-terminal helix conformations of Cx43-gate-covering (GCN), pore-lining (PLN), and flexible intermediate (FIN)-that are randomly distributed in purified GJICh particles. The conformational equilibrium shifts to GCN by cholesteryl hemisuccinates and to PLN by C-terminal truncations and at varying pH. While GJIChs that mainly comprise GCN protomers are occluded by lipids, those containing conformationally heterogeneous protomers show markedly different pore sizes. We observe an α-to-π-helix transition in the first transmembrane helix, which creates a side opening to the membrane in the FIN and PLN conformations. This study provides basic structural information to understand the mechanisms of action and regulation of Cx43 GJICh.

Development of in ovo-compatible NS1-truncated live attenuated influenza vaccines by modulation of hemagglutinin cleavage and polymerase acidic X frameshifting sites.

Emerging avian influenza viruses pose a high risk to poultry production, necessitating the need for more broadly protective vaccines. Live attenuated influenza vaccines offer excellent protective efficacies but their use in poultry farms is discouraged due to safety concerns related to emergence of reassortant viruses. Vaccination of chicken embryos inside eggs (in ovo) induces early immunity in young chicks while reduces the safety concerns related to the use of live vaccines on farms. However, in ovo vaccination using influenza viruses severely affects the egg hatchability. We previously engineered a high interferon-inducing live attenuated influenza vaccine candidate with an enhanced protective efficacy in chickens. Here, we asked whether we could further modify this high interferon-inducing vaccine candidate to develop an in ovo-compatible live attenuated influenza vaccine. We first showed that the enhanced interferon responses induced by the vaccine is not enough to attenuate the virus in ovo. To reduce the pathogenicity of the virus for chicken embryos, we replaced the hemagglutinin cleavage site of the H7 vaccine virus (PENPKTR/GL) with that of the H6-subtype viruses (PQIETR/GL) and disrupted the ribosomal frameshifting site responsible for viral polymerase acidic X protein expression. In ovo vaccination of chickens with up to 105 median egg infectious dose of the modified vaccine had minimal effects on hatchability while protecting the chickens against a heterologous challenge virus at two weeks of age. This study demonstrates that targeted genetic mutations can be applied to further attenuate and enhance the safety of live attenuated influenza vaccines to develop future in ovo vaccines for poultry.

Frequency tunable superflash based on an electromagnetically induced transparency (EIT).

We present a new controllable superflash, a maximum transient peak at the falling edge of a square pulse, using a three-level electromagnetically induced transparency (EIT). The superflash in a two-level system occurs at a certain value of the detuning of the probe laser (Δpeak) when the optical depth (OD) of the medium is sufficiently large and constant. Here, we show the external tunability of the Δpeak for obtaining the maximum transient peak by introducing a three-level EIT. Owing to the EIT dispersion properties, we effectively tune the phase of the forward-scattered light (Es) by externally controlling the EIT coupling light intensities associated with the Rabi frequency (Ωc). When the incident light is turned off, the total transmitted field (Et) experiences an out-of-phase shift, producing a peak intensity that is three times higher than the input. We observe that this new class of superflash (Type II) occurs near the EIT window and exhibits inverse-linearity of the OD, which is in contrast with the characteristics of the previously reported two-level superflash (Type I). Furthermore, we find the quadratic nature of tunability in Δpeak(Ωc).The new tunability of the superflash by the Rabi frequency may facilitate more rapid and effective control of the superflash compared to a passive optical medium.

Application of Metaverse Service to Healthcare Industry: A Strategic Perspective.

This study is to explore a state of the art in metaverse service that is an emerging issue in applying it to the healthcare industry. The purpose of this study is to provide applicable strategic scenarios for effective metaverse service planning and implementation in healthcare settings. This study is focused on metaverse service as a business model. Thus, related literatures of metaverse service are reviewed in various aspects in healthcare industry. An exploratory approach is used to analyze current qualitative data characterizing healthcare metaverse service business positions and derive applicable strategies from business trends of current metaverse services. Several cases are examined based on the data obtained from various sources of healthcare and other related industries. This study synthesizes finding results and suggests applicable strategies of metaverse service in the healthcare industry. This study will facilitate strategic decision-making and policy-making processes to pursue a business opportunity development through an application of a metaverse service in healthcare and similar settings.

Monitoring energy balance through clinical and serum biomarkers in patients with hematologic malignancies undergoing chemotherapy.

Despite widespread concern about energy imbalance due to tumor and chemotherapy-related side effects, little is known about detailed variations in energy input, metabolic rate, and physical activity. This study explored changes in energy balance components and serum biomarkers of patients with hematologic malignancies undergoing chemotherapy. Our prospective study included 40 patients with hematologic malignancies hospitalized for chemotherapy. We measured energy balance components, physical function, and serum biomarkers at baseline and weekly after chemotherapy for 3 weeks. Significant weight loss, representing negative energy balance, occurred at 2 (p = 0.002) and 3 weeks (p < 0.001) post-chemotherapy. Statistically reduced oral intake was observed at 3 weeks post-chemotherapy (p = 0.040), and resting energy expenditure statistically decreased according to Harris-Benedict equation, but not to Penn State University equation. Physical function according to DEMMI score decreased significantly at 3 weeks post-chemotherapy (p = 0.002). Serum biomarker analysis demonstrated significant changes in albumin, total protein, CXCL13, and GDF15, with exception of leptin. Although conventional serum biomarkers (total protein and albumin) did not reach pathological states despite their statistical differences, subgroup analysis showed CXCL13 in weight loss group and GDF15 in reduced oral intake group were significantly changed. Over half of patients (65.0%, n = 26) suffered from energy imbalance associated with weight loss and reduced oral intake during chemotherapy. Serial laboratory results suggested that novel biomarkers (CXCL13, GDF15) could be correlated with cachexic state and reduced food intake. Monitoring clinical and serum biomarkers associated with energy balance together can help identify needs for nutritional support in patients with hematologic malignancies undergoing chemotherapy.

Effects of Hydrodilatation With Corticosteroid Injection and Biomechanical Properties in Patients With Adhesive Capsulitis After Breast Cancer Surgery.

OBJECTIVE: To compare the biomechanical properties of the glenohumeral joint capsule between adhesive capsulitis (AC) after breast cancer surgery and idiopathic AC and demonstrate the effects of hydrodilatation (HD) with corticosteroid injection for AC after breast cancer surgery. METHODS: Twenty-three prospective patients with AC after breast cancer surgery (BC group) and 44 retrospective patients with idiopathic AC without breast cancer (CON group) underwent HD with corticosteroid injection and home exercise training. We compared their biomechanical characteristics (capsular capacity, maximal pressure, and capsular stiffness). In the BC group, the passive range of motion (ROM) of the affected shoulder and a questionnaire (Shoulder Pain and Disability Index [SPADI]) were evaluated at baseline and 2 and 4 weeks after treatment. RESULTS: The BC group showed higher biomechanical characteristics (maximal pressure and capsular stiffness) than did the CON group. The mean maximal pressure and capsular stiffness were 519.67±120.90 mmHg and 19.69±10.58 mmHg/mL in the BC group and 424.78±104.42 mmHg and 11.55±7.77 mmHg/mL in the CON group (p=0.002 and p=0.001, respectively). And, the BC group showed significant improvements in all ROMs (abduction, flexion, and external rotation) and the SPADI pain and disability sub-scores following the treatment. CONCLUSION: The glenohumeral joint capsular stiffness was greater in the patients with AC after breast cancer surgery than in those with idiopathic AC. HD with corticosteroid injection was effective in treating AC after breast cancer surgery.

Sulfated Glucuronorhamnoxylan from Capsosiphon fulvescens Ameliorates Osteoporotic Bone Resorption via Inhibition of Osteoclastic Cell Differentiation and Function In Vitro and In Vivo.

Excessive osteoclast differentiation and/or bone resorptive function causes a gradual loss of bone, leading to the pathogenesis of bone diseases such as osteoporosis (OP). In this study, a sulfated glucuronorhamnoxylan polysaccharide (designated SPS-CF) of the green alga Capsosiphon fulvescens was evaluated for anti-osteoporotic activity using osteoclastic cells differentiated from RAW264.7 macrophages by receptor activator of NF-κB ligand (RANKL) treatment and ovariectomized (OVX) female mice as a postmenopausal OP model. With negligible cytotoxicity, SPS-CF (50 µg/mL) significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity, actin ring formation, and expression of matrix metalloproteinase 9 (MMP-9), cathepsin K, TRAF6, p-Pyk2, c-Cbl, c-Src, gelsolin, carbonic anhydrase II (CA II), and integrin ß3, indicating that SPS-CF inhibits the differentiation and bone resorptive function of osteoclasts. Removal of sulfate groups from SPS-CF abolished its anti-osteoclastogenic activities, demonstrating that sulfate groups are critical for its activity. Oral administration of SPS-CF (400 mg/kg/day) to OVX mice significantly augmented the bone mineral density (BMD) and serum osteoprotegerin (OPG)/RANKL ratio. These results demonstrated that SPS-CF exerts significant anti-osteoporotic activity by dampening osteoclastogenesis and bone resorption via downregulation of TRAF6-c-Src-Pyk2-c-Cbl-gelsolin signaling and augmentation of serum OPG/RANKL ratios in OVX mice, suggesting that SPS-CF can be a novel anti-osteoporotic compound for treating postmenopausal OP.

Analysis of clinical phenotypes of neuropathic symptoms in patients with type 2 diabetes: A multicenter study.

AIMS/INTRODUCTION: We investigated the classification of diabetic peripheral neuropathy (DPN) patients by subjective symptoms, and identification of the relationship between the patterns and intensities of symptoms and the clustered groups of DPN patients. MATERIALS AND METHODS: This multicenter study analyzed epidemiological data and sensory symptoms of 649 patients with DPN. Cluster analysis was carried out to identify subgroups of patients with characteristic symptom profiles. Factor analysis was carried out to investigate the symptom patterns of the clustered groups of DPN patients. RESULTS: Three clusters of patients with DPN were identified: severe symptoms with decreased quality of life (cluster 1, n = 119, 18.3%), predominantly insensate symptoms with relatively good quality of life (cluster 2, n = 318, 49.0%), and moderate pain intensity and decreased quality of life (cluster 3, n = 204, 31.4%). The frequency of symptoms on each item of the Michigan Neuropathy Screening Instrument questionnaire showed a similar distribution according to pain intensities along with the three clusters. CONCLUSIONS: Our study supports the hypothesis that diversity in sensory symptoms exists in patients with DPN. Heterogeneity in DPN patients should be taken into account for a more stratified or individualized treatment approach. Based on a multicenter study, we identified three clusters of patients with DPN. Our research supports the hypothesis that diversity in sensory symptoms exists in patients with DPN. Heterogeneity in DPN patients should be taken into account for a more stratified or individualized treatment approach.

Natural aging course of lumbar extensor muscle mass and strength in community-dwelling older women: a 1-year prospective observational study.

BACKGROUND: Although the loss of skeletal limb muscle mass and muscle strength in the elderly have been demonstrated, the aging process of the back muscles to maintain core stability is not well known. This 1-year prospective observational study aimed to investigate the natural aging course of the lumbar extensor muscles (LEMs) compared with the extremity muscles and determine whether muscle strength or mass decreases more in community-dwelling older women. METHODS: Twenty-four older urban-dwelling women aged 70 years or older were initially enrolled. Their demographic variables, conventional and spinal sarcopenia indices, and functional outcome parameters were evaluated. We also measured back extensor strength, radiological parameters for spinal sagittal balance on whole-spine radiography, and volumetric parameters of the LEM on computed tomography. RESULTS: After the exclusion of 6 subjects, 18 older women were finally analyzed. All variables related to extremity muscle mass, muscle strength, physical performance, and LEM volume declined over the study period, but the changes were insignificant. However, back extensor strength decreased significantly (median, first, and third quartile: 35.20 [30.80, 44.00] N to 31.40 [29.25, 37.90] N, P = 0.026). Among spinal sagittal balance-related parameters, lumbar lordosis (44.25 [39.30, 47.35]° to 43.15 [31.43, 45.75]°, P = 0.043) and sagittal vertical axis (33.85 [3.57, 58.75] mm to 45.15 [25.35, 58.68] mm, P = 0.004) showed significant changes during the study. CONCLUSIONS: When the natural aging course of LEM in women aged 70 years or older was observed for 1 year, muscle mass decreased less than back extensor strength and spinal sagittal balance. Measurements of back extensor strength and spinal sagittal balance are necessary for the clinical evaluation of spinal aging.

Nanomaterial-Embedded DNA Films on 2D Frames.

Recently, 3D printing has provided opportunities for designing complex structures with ease. These printed structures can serve as molds for complex materials such as DNA and cetyltrimethylammonium chloride (CTMA)-modified DNA that have easily tunable functionalities via the embedding of various nanomaterials such as ions, nanoparticles, fluorophores, and proteins. Herein, we develop a simple and efficient method for constructing DNA flat and curved films containing water-soluble/thermochromatic dyes and di/trivalent ions and CTMA-modified DNA films embedded with organic light-emitting molecules (OLEM) with the aid of 2D/3D frames made by a 3D printer. We study the Raman spectra, current, and resistance of Cu2+-doped and Tb3+-doped DNA films and the photoluminescence of OLEM-embedded CTMA-modified DNA films to better understand the optoelectric characteristics of the samples. Compared to pristine DNA, ion-doped DNA films show noticeable variation of Raman peak intensities, which might be due to the interaction between the ion and phosphate backbone of DNA and the intercalation of ions in DNA base pairs. As expected, ion-doped DNA films show an increase of current with an increase in bias voltage. Because of the presence of metallic ions, DNA films with embedded ions showed relatively larger current than pristine DNA. The photoluminescent emission peaks of CTMA-modified DNA films with OLEMRed, OLEMGreen, and OLEMBlue were obtained at the wavelengths of 610, 515, and 469 nm, respectively. Finally, CIE color coordinates produced from CTMA-modified DNA films with different OLEM color types were plotted in color space. It may be feasible to produce multilayered DNA films as well. If so, multilayered DNA films embedded with different color dyes, ions, fluorescent materials, nanoparticles, proteins, and drug molecules could be used to realize multifunctional physical devices such as energy harvesting and chemo-bio sensors in the near future.

The immediate impact of physical function and quality of life after hematopoietic stem cell transplantation.

PURPOSE: Although hematopoietic stem cell transplantation (HSCT) is a curative treatment for hematologic malignancies, HSCT survivors often experience declined physical function and quality of life (QoL). However, the physical function and QoL changes in acute post-transplant patients remain unclear. This study aimed to investigate the impact of HSCT on physical function. METHOD: This retrospective control study included 107 HSCT patients. Physical function was evaluated weekly from admission to discharge using the de Morton Mobility Index (DEMMI). Impaired physical function was defined as a baseline raw ordinal DEMMI score of < 17 and a decrease of ≥ 2 points. We collected the Visual Analog Scale (VAS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Zung Self-rating Depression Scale (SDS) at enrollment and discharge. RESULTS: Based on the DEMMI scores, 41 patients (38.3%) showed impaired physical function. A notable decrease in the DEMMI score was found in the first week after HSCT. In the EORTC QLQ-C30, physical function differed between the groups at admission and discharge. The good physical function group showed better cognitive function and social function. For the SDS, the impaired physical function group showed significantly higher depression at discharge. CONCLUSION: A third of the patients showed physical impairment during the acute transplant period. Patients with low physical function suffered more from depression and lower QoL. Evaluating patients' pre-transplant physical function and early detection is needed as impaired physical function mainly occurs at 1 week post-transplant.