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Fibrinogen-fibrin degradation products (DR-70) are derived from tumor cells or metastases. Our previous study reported the diagnostic values in dogs with tumors, but no research has yet to be conducted to establish DR-70 as a prognostic marker. Herein, we investigated changes in DR-70 concentrations and disease courses in dogs with tumors. Overall survival time (OST) analysis was performed in 195 dogs with tumors, stratified with a recommended cut-off (1.514 µg/mL). Continual DR-70 measurements were performed during the medical interventions of 27 dogs with neoplasms. Clinical conditions and medical records were retrospectively reviewed. According to a cut-off value, dogs with plasma DR-70 concentrations above 1.514 µg/mL had shorter survival rates than those with concentrations below this threshold. In cases with complete or partial remission in response to treatment, the DR-70 concentration was decreased compared with that at the first visit, whereas it was increased in patients with disease progression. Our study suggested that changes in DR-70 concentration can be used as a prognostic biomarker for canine neoplasms. Furthermore, increased plasma DR-70 levels might be associated with shorter survival, and DR-70 concentrations may reflect responses to medical intervention.

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Magnetars are neutron stars with extremely high magnetic fields (≳1014 gauss) that exhibit various X-ray phenomena such as sporadic subsecond bursts, long-term persistent flux enhancements and variable rotation-period derivative1,2. In 2020, a fast radio burst (FRB), akin to cosmological millisecond-duration radio bursts, was detected from the Galactic magnetar SGR 1935+2154 (refs. 3-5), confirming the long-suspected association between some FRBs and magnetars. However, the mechanism for FRB generation in magnetars remains unclear. Here we report the X-ray observation of two glitches in SGR 1935+2154 within a time interval of approximately nine hours, bracketing an FRB that occurred on 14 October 20226,7. Each glitch involved a significant increase in the magnetar's spin frequency, being among the largest abrupt changes in neutron-star rotation8-10 observed so far. Between the glitches, the magnetar exhibited a rapid spin-down phase, accompanied by an increase and subsequent decline in its persistent X-ray emission and burst rate. We postulate that a strong, ephemeral, magnetospheric wind11 provides the torque that rapidly slows the star's rotation. The trigger for the first glitch couples the star's crust to its magnetosphere, enhances the various X-ray signals and spawns the wind that alters magnetospheric conditions that might produce the FRB.

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BACKGROUND: Tumor biomarkers have used widely in clinical oncology in human medicine. Only a few studies have evaluated the clinical utility of tumor biomarkers for veterinary medicine. A test for fibrinogen and fibrin degradation products (DR-70) has been proposed as an ideal biomarker for tumors in humans. The clinical value of DR-70 for veterinary medicine however has yet to be determined. OBJECTIVES: Investigate the diagnostic value of DR-70 concentrations by comparing them between healthy dogs and dogs with tumors. ANIMALS: Two hundred sixty-three dogs with different types of tumors were included. Sixty healthy dogs also were recruited for comparison. METHODS: The DR-70 concentrations were measured in all recruited individuals by ELISA. Clinical conditions were categorized based on histopathology, cytology, ultrasound examination, radiology, clinical findings, and a combination of these tests. RESULTS: The median concentration of DR-70 was 2.130 ± 0.868 µg/mL in dogs with tumors, which was significantly higher than in healthy dogs (1.202 ± 0.610 µg/mL; P < .0001). With a cut-off of 1.514 µg/mL, the sensitivity and specificity of DR-70 were 84.03% and 78.33%, respectively. The area under curve was 0.883. The DR-70 concentration can be an effective tumor biomarker in veterinary medicine. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased DR-70 concentrations were not affected by tumor type, sex, age, or body weight. However, in dogs with metastatic mast cell tumors and oral malignant melanoma, DR-70 concentrations were significantly increased. Additional studies, including more dogs with nonneoplastic diseases, are needed to further evaluate the usefulness of DR-70 as a tumor biomarker.

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Pollution in human-made fishing ports caused by petroleum from boats, dead fish, toxic chemicals, and effluent poses a challenge to the organisms in seawater. To decipher the impact of pollution on the microbiome, we collected surface water from a fishing port and a nearby offshore island in northern Taiwan facing the Northwestern Pacific Ocean. By employing 16S rRNA gene amplicon sequencing and whole-genome shotgun sequencing, we discovered that Rhodobacteraceae, Vibrionaceae, and Oceanospirillaceae emerged as the dominant species in the fishing port, where we found many genes harboring the functions of antibiotic resistance (ansamycin, nitroimidazole, and aminocoumarin), metal tolerance (copper, chromium, iron and multimetal), virulence factors (chemotaxis, flagella, T3SS1), carbohydrate metabolism (biofilm formation and remodeling of bacterial cell walls), nitrogen metabolism (denitrification, N2 fixation, and ammonium assimilation), and ABC transporters (phosphate, lipopolysaccharide, and branched-chain amino acids). The dominant bacteria at the nearby offshore island (Alteromonadaceae, Cryomorphaceae, Flavobacteriaceae, Litoricolaceae, and Rhodobacteraceae) were partly similar to those in the South China Sea and the East China Sea. Furthermore, we inferred that the microbial community network of the cooccurrence of dominant bacteria on the offshore island was connected to dominant bacteria in the fishing port by mutual exclusion. By examining the assembled microbial genomes collected from the coastal seawater of the fishing port, we revealed four genomic islands containing large gene-containing sequences, including phage integrase, DNA invertase, restriction enzyme, DNA gyrase inhibitor, and antitoxin HigA-1. In this study, we provided clues for the possibility of genomic islands as the units of horizontal transfer and as the tools of microbes for facilitating adaptation in a human-made port environment.

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Importance: Annual administration of the influenza vaccine (fluVc) is currently the most effective method of preventing the influenza virus in older adults. However, half of adults older than 65 years remain unvaccinated in Taiwan, possibly because of concern about adverse events, such as Bell palsy (BP). Currently, studies on the association between fluVc and risk of BP are inconsistent. Objective: To determine whether the incidence of BP increases following fluVc in older adults. Design, Setting, and Participants: A self-controlled case series study design was used. Days 1 through 7, days 8 through 14, days 15 through 30, and days 31 through 60 following fluVc were identified as risk intervals, and days 61 through 180 were considered the control interval. A total of 4367 vaccinated individuals aged 65 years or older who developed BP within 6 months following fluVc were enrolled. Population-based retrospective claims data were obtained between 2010 and 2017; data were analyzed from April 2022 through September 2022. Exposure: Government-funded seasonal fluVc. Main Outcomes and Measures: The outcome of interest was BP onset in risk intervals compared with control intervals. Three or more consecutive diagnoses of BP within 60 days following fluVc were used as the definition of a patient with BP. Poisson regression was used to analyze the incidence rate ratio (IRR) of risk intervals compared with control intervals. Results: In total, 13 261 521 patients who received the fluVc were extracted from the National Health Insurance Research Database in Taiwan from January 1, 2010, to December 31, 2017. Of those, 7 581 205 patients older than 65 years old met the inclusion criteria. The number of patients with BP diagnosed within 6 months following fluVc enrolled for risk analysis was 4367 (mean [SD] age, 74.19 [5.97] years; 2349 [53.79%] female patients). The incidence rate of BP among all observed fluVc older adults was 57.87 per 100 000 person-years. The IRRs for BP on days 1 through 7, days 8 through 14, and days 15 through 30 were 4.18 (95% CI, 3.82-4.59), 2.73 (95% CI, 2.45-3.05), and 1.67 (95% CI, 1.52-1.84), respectively. However, there was no increase during days 31 through 60 (IRR, 1.06; 95% CI, 0.97-1.16). The postvaccination risk of BP was consistent across all subgroups stratified by sex, age group, and baseline conditions. Conclusions and Relevance: The present self-controlled case series indicated that the risk of BP in individuals older than 65 years increased within the first month, especially within the first week, following fluVc. But overall, the adverse event rate of BP was low, and considering the morbidity and mortality of influenza infection, the benefits of fluVc still outweigh the risks.

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Understanding integrative approaches to mental health care can improve the responsiveness of the mental health system. Complementary and alternative medicine (CAM) use is on the rise. Research documents that many mental health consumers use CAM. This exploratory study attempts to advance awareness of CAM in mental health by examining mental health consumers' usage of CAM, their experiences in discussing CAM use with providers, and how CAM use relates to mental health recovery. Results show that 72% of the sample uses such methods, and CAM use is associated with recovery. About 54% of respondents feel CAM combined with medication is more effective than medication alone, and many endorse positive beliefs about CAM. Most consumers shared CAM use with their providers, but when they did not, the main reasons were fear of provider judgment and provider attitudes being a deterrent.

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Critical physical systems with large numbers of molecules can show universal and scaling behaviors. It is of interest to know whether human societies with large numbers of people can show the same behaviors. Here, we use network theory to analyze Chinese history in periods 209 BCE-23 CE and 515-618 CE) related to the Western Han-Xin Dynasty and the late Northern Wei-Sui Dynasty, respectively. Two persons are connected when they appear in the same historical event. We find that the historical networks from two periods separated about 500 years have interesting universal and scaling behaviors, and they are small-world networks; their average cluster coefficients as a function of degree are similar to the network of movie stars. In the historical networks, the persons with larger degrees prefer to connect with persons with a small degree; however, in the network of movie stars, the persons with larger degrees prefer to connect with persons with large degrees. We also find an interesting similar mechanism for the decline or collapse of historical Chinese dynasties. The collapses of the Xin dynasty (9-23 CE) and the Sui dynasty (581-618 CE) were initiated from their arrogant attitude toward neighboring states.

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Recessive PJVK mutations that cause a deficiency of pejvakin, a protein expressed in both sensory hair cells and first-order neurons of the inner ear, are an important cause of hereditary hearing impairment. Patients with PJVK mutations garner limited benefits from cochlear implantation; thus, alternative biological therapies may be required to address this clinical difficulty. The synthetic adeno-associated viral vector Anc80L65, with its wide tropism and high transduction efficiency in various inner ear cells, may provide a solution. We delivered the PJVK transgene to the inner ear of Pjvk mutant mice using the synthetic Anc80L65 vector. We observed robust exogenous pejvakin expression in the hair cells and neurons of the cochlea and vestibular organs. Subsequent morphologic and audiologic studies demonstrated significant restoration of spiral ganglion neuron density and hair cells in the cochlea, along with partial recovery of sensorineural hearing impairment. In addition, we observed a recovery of vestibular ganglion neurons and balance function to WT levels. Our study demonstrates the utility of Anc80L65-mediated gene delivery in Pjvk mutant mice and provides insights into the potential of gene therapy for PJVK-related inner ear deficits.

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The common carp is a hypoxia-tolerant fish, and the understanding of its ability to live in low-oxygen environments has been applied to human health issues such as cancer and neuron degeneration. Here, we investigated differential gene expression changes during hypoxia in five common carp organs including the brain, the gill, the head kidney, the liver, and the intestine. Based on RNA sequencing, gene expression changes under hypoxic conditions were detected in over 1800 genes in common carp. The analysis of these genes further revealed that all five organs had high expression-specific properties. According to the results of the GO and KEGG, the pathways involved in the adaptation to hypoxia provided information on responses specific to each organ in low oxygen, such as glucose metabolism and energy usage, cholesterol synthesis, cell cycle, circadian rhythm, and dopamine activation. DisGeNET analysis showed that some human diseases such as cancer, diabetes, epilepsy, metabolism diseases, and social ability disorders were related to hypoxia-regulated genes. Our results suggested that common carp undergo various gene regulations in different organs under hypoxic conditions, and integrative bioinformatics may provide some potential targets for advancing disease research.

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ABSTRACT: We presented here a 71-year-old man with a history of thyroid cancer post total thyroidectomy and 131I ablation and right renal cell carcinoma post right partial nephrectomy. He reported persistent chest tightness and pain after the first dose of the Moderna COVID-19 (mRNA-1273) vaccine. Thus, coronary heart disease was suspected, and the patient was referred for MPI (myocardial perfusion imaging). Focal 201Tl uptake in the left axillary region was found incidentally on MPI, and SPECT/CT revealed enlarged benign-looking lymph nodes. The diagnostic is in favor of reactive hyperplasia after the intramuscular injection of vaccine into left deltoid muscle.

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Recessive variants of the SLC26A4 gene are an important cause of hereditary hearing impairment. Several transgenic mice with different Slc26a4 variants have been generated. However, none have recapitulated the auditory phenotypes in humans. Of the SLC26A4 variants identified thus far, the p.T721M variant is of interest, as it appears to confer a more severe pathogenicity than most of the other missense variants, but milder pathogenicity than non-sense and frameshift variants. Using a genotype-driven approach, we established a knock-in mouse model homozygous for p.T721M. To verify the pathogenicity of p.T721M, we generated mice with compound heterozygous variants by intercrossing Slc26a4+/T721M mice with Slc26a4919-2A>G/919-2A>G mice, which segregated the c.919-2A > G variant with abolished Slc26a4 function. We then performed serial audiological assessments, vestibular evaluations, and inner ear morphological studies. Surprisingly, both Slc26a4T721M/T721M and Slc26a4919-2A>G/T721M showed normal audiovestibular functions and inner ear morphology, indicating that p.T721M is non-pathogenic in mice and a single p.T721M allele is sufficient to maintain normal inner ear physiology. The evidence together with previous reports on mouse models with Slc26a4 p.C565Y and p.H723R variants, support our speculation that the absence of audiovestibular phenotypes in these mouse models could be attributed to different protein structures at the C-terminus of human and mouse pendrin.

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During development, erythroid cells are generated by two waves of hematopoiesis. In zebrafish, primitive erythropoiesis takes place in the intermediate cell mass region, and definitive erythropoiesis arises from the aorta-gonad mesonephros. TALE-homeoproteins Meis1 and Pbx1 function upstream of GATA1 to specify the erythroid lineage. Embryos lacking Meis1 or Pbx1 have weak gata1 expression and fail to produce primitive erythrocytes. Nevertheless, the underlying mechanism of how Meis1 and Pbx1 mediate gata1 transcription in erythrocytes remains unclear. Here we show that Hif1α acts downstream of Meis1 to mediate gata1 expression in zebrafish embryos. Inhibition of Meis1 expression resulted in suppression of hif1a expression and abrogated primitive erythropoiesis, while injection with in vitro-synthesized hif1α mRNA rescued gata1 transcription in Meis1 morphants and recovered their erythropoiesis. Ablation of Hif1α expression either by morpholino knockdown or Crispr-Cas9 knockout suppressed gata1 transcription and abrogated primitive erythropoiesis. Results of chromatin immunoprecipitation assays showed that Hif1α associates with hypoxia-response elements located in the 3'-flanking region of gata1 during development, suggesting that Hif1α regulates gata1 expression in vivo. Together, our results indicate that Meis1, Hif1α, and GATA1 indeed comprise a hierarchical regulatory network in which Hif1α acts downstream of Meis1 to activate gata1 transcription through direct interactions with its cis-acting elements in primitive erythrocytes.

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Heart disease is the second most common cause of mortality in Taiwan, mainly coronary artery disease (CAD).Quantitative coronary blood flow has been collected by dynamic single-photon emission computed tomography (Dynamic SPECT/CT) for CAD diagnosis in previous studies. However, few studies defined the extent of left ventricle (LV) ischemia on Dynamic SPECT/CT for predicting significant coronary artery stenosis. This study evaluates the extent of LV ischemic blockage in patients suspected of CAD who were referred by cardiologists. A total of 181 patients with suspected CAD were enrolled. They underwent 99mTc-Sestamibi (MIBI) Dynamic SPECT/CT survey before cardiac intervention. Dynamic SPECT/CT has better sensitivity (88%), specificity (96%), and accuracy (94%) compared with those of semi-quantitative MIBI MPI (more than 10%). Results indicated that5% of the LV ischemic extent can yield positive PCI results (>70% stenosis in coronary arteries) compared with the moderate abnormal extent of at least 15% of LV. When the percentage of combined moderate abnormal extent and ischemia extent of LV reaches 27.3%, positive PCI results may be indicated. This study revealed Dynamic SPECT/CT has greater sensitivity, specificity, and accuracy as compared with MPI. Thus, the severity of abnormal perfusion extent of LV on Dynamic SPECT/CT might be beneficial to predict positive PCI results in patients with significant suspicion CAD.

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We present a case of CAD with anteroseptal MI after stent insertion for revascularization due to symptoms presented. MPI with dynamic SPECT/CT provided useful information in terms of flow parameters and matched territories of stenting results as well as providing coronary artery flow phenomenon underwent PCI. In this case, dynamic SPECT/CT may minimize errors with proper stents treatment, especially for controversial MPI results.

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Recessive variants of the SLC26A4 gene are globally a common cause of hearing impairment. In the past, cell lines and transgenic mice were widely used to investigate the pathogenicity associated with SLC26A4 variants. However, discrepancies in pathogenicity between humans and cell lines or transgenic mice were documented for some SLC26A4 variants. For instance, the p.C565Y variant, which was reported to be pathogenic in humans, did not exhibit functional pathogenic consequences in cell lines. To address the pathogenicity of p.C565Y, we used a genotype-based approach in which we generated knock-in mice that were heterozygous (Slc26a4+/C565Y), homozygous (Slc26a4C565Y/C565Y), and compound heterozygous (Slc26a4919-2A>G/C565Y) for this variant. Subsequent phenotypic characterization revealed that mice with these genotypes demonstrated normal auditory and vestibular functions, and normal inner-ear morphology and pendrin expression. These findings indicate that the p.C565Y variant is nonpathogenic for mice, and that a single p.C565Y allele is sufficient to maintain normal inner-ear physiology in mice. Our results highlight the differences in pathogenicity associated with certain SLC26A4 variants between transgenic mice and humans, which should be considered when interpreting the results of animal studies for SLC26A4-related deafness.

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Giant radio pulses (GRPs) are sporadic bursts emitted by some pulsars that last a few microseconds and are hundreds to thousands of times brighter than regular pulses from these sources. The only GRP-associated emission outside of radio wavelengths is from the Crab Pulsar, where optical emission is enhanced by a few percentage points during GRPs. We observed the Crab Pulsar simultaneously at x-ray and radio wavelengths, finding enhancement of the x-ray emission by 3.8 ± 0.7% (a 5.4σ detection) coinciding with GRPs. This implies that the total emitted energy from GRPs is tens to hundreds of times higher than previously known. We discuss the implications for the pulsar emission mechanism and extragalactic fast radio bursts.

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Hypoxia-inducible factors (HIFs) and survivin (Birc5) genes are often considered important cancer drug targets for molecularly targeted therapy, as both genes play important roles in the cellular differentiation and development of neuronal cells. Pathway enrichment analysis is predominantly applied when interpreting the correlated behaviors of activated gene clusters. Traditional enrichment analysis is evaluated via p-values only, regardless of gene expression fold-change levels, gene locations, and possible hidden interactions within a pathway. Here, we combined these factors to retrieve significant pathways, as compared with traditional approaches. We performed RNA-seq analyses on Birc5a and HIF2α knocked down in zebrafish during the embryogenesis stage. Regarding Birc5a, two additional biological pathways, sphingolipid metabolism and herpes simplex infection, were identified; whereas for HIF2α, four biological pathways were re-identified, including ribosome biogenesis in eukaryotes, proteasome, purine metabolism, and complement and coagulation cascades. Our proposed approaches identified additional significant pathways directly related to cell differentiation or cancer, also providing comprehensive mechanisms for designing further biological experiments.

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Esophageal squamous cell carcinoma (ESCC) is a major cancer prevalent in Asian males. Pretreatment tumor burden can be prognostic for ESCC. We studied the prognostic value of metabolic parameters of 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) and the serum squamous cell carcinoma antigen (SCC-Ag) level in node-negative stage II ESCC patients. Eighteen males underwent staging evaluation were included. The volume-based metabolic parameters derived from 18F-FDG PET/CT, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were obtained using the PET Volume Computer Assisted Reading application. The Spearman correlation coefficients were calculated to assess the relationship between metabolic parameters and pretreatment serum SCC-Ag levels. Based on the 5-year follow-up, patients were sub-divided into the demised and the stable groups. Potential prognostic value was assessed by independent t-test and the Mann-Whitney U test. The association of overall survival was assessed using univariate and multivariate Cox regression analyses. The demised group showed significant higher values in serum SCC-Ag, as well as in MTV and TLG, but not SUVmax and SUVmean. The SUVmax, MTV, TLG, and serum SCC-Ag showed significant association with overall survival. Our findings suggest potential usage of pretreatment volume-based metabolic parameters of 18F-FDG PET/CT and serum SCC-Ag as prognostic factors for node-negative stage II ESCC patients.

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ABSTRACT: 99mTc-TRODAT-1 SPECT/CT has been used to evaluate parkinsonian disorders. We present an interesting case of a 63-year-old woman with progressive tremulousness over the left side of the body for 6 months. Bilateral thalamic glioma with reduced uptake was shown on 99mTc-TRODAT-1 SPECT/CT. Secondary parkinsonism was impressed in this case.

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