The combined use of the Charlson Comorbidity Index and National Early Warning Score 2 helps predict the prognosis of candidemia.

BACKGROUND: The National Early Warning Score 2 (NEWS2) standardizes assessment and response to acute illnesses using vital signs. Whether NEWS2 is useful in predicting the prognosis of candidemia remains to be determined. METHODS: Our study, conducted as a rigorous and retrospective analysis, examined patients with candidemia who were hospitalized between January 2014 and December 2023. We assessed candidemia severity using the Pitt Bacteremia Score (PBS) and NEWS2, while the Charlson Comorbidity Index (CCI) was used to assess underlying medical conditions. The endpoint was all-cause mortality within 30 days of candidemia onset, ensuring comprehensive evaluation of the patient's prognosis. RESULTS: Overall, 93 patients with candidemia were included. The 30-day all-cause mortality rate was 29.0 %. The area under the receiver operating characteristic curve (AUC) for CCI, PBS, and NEWS2 were 0.87 (95 % confidence interval [CI]: 0.80-0.95), 0.75 (95 % CI: 0.66-0.85), and 0.92 (95 % CI: 0.87-0.97), respectively, for predicting the 30-day mortality in patients with candidemia. The AUC values for CCI combined with PBS and NEWS2 were 0.89 (95 % CI: 0.83-0.96) and 0.96 (95 % CI: 0.93-1.00) for predicting the 30-day mortality in candidemia. Among the items that were significant in the univariate analysis, multivariate analysis showed that the combination of NEWS2 ≥ 10 and CCI ≥4 was the helpful prognostic factor for 30-day mortality. CONCLUSIONS: The combination of NEWS2 ≥ 10 and CCI ≥4 scores may be useful in predicting the risk of 30-day mortality in patients with candidemia.

False-Positive Asymmetrical Tongue Muscle 18F-FDG Uptake in Hypoglossal Nerve Paralysis Following Lymph Node Dissection in a Pediatric Patient with Malignant Rhabdoid Tumor of the Neck.

BACKGROUND: Although positron emission tomography combined with computed tomography (PET-CT) plays an important role in detecting various types of childhood malignancy, it has low positive predictive value, owing to the nonspecific uptake of 18F-fluorodeoxyglucose (FDG) by normal tissue in various benign conditions. CASE SUMMARY: A 5-year-old male patient with a malignant rhabdoid tumor originating in the left neck underwent primary tumor resection concurrently with ipsilateral lymph node dissection after receiving neoadjuvant chemotherapy consisting of cyclophosphamide, carboplatin, etoposide, vincristine, and doxorubicin. He later received the same adjuvant chemotherapy as well as proton therapy for the primary tumor. Sixteen months after completing the initial therapy, follow-up PET-CT revealed a novel area of glucose hypermetabolism in the right side of the tongue, which was suspected of being a recurrence. However, a physical examination and magnetic resonance imaging (MRI) demonstrated no evidence of tumor recurrence. The patient had a significant leftward deviation of the tongue, suggesting left hypoglossal nerve paralysis. Denervation of the ipsilateral intrinsic tongue muscles secondary to the treatment had caused atrophy in the ipsilateral muscles and compensatory hypertrophy in the contralateral muscles, which increased FDG uptake. Physicians should carefully confirm any diagnosis of a locally recurrent tumor because PET-CT often produces ambiguous findings.

Accelerated Adiabatic Passage of a Single Electron Spin Qubit in Quantum Dots.

Adiabatic processes can keep the quantum system in its instantaneous eigenstate, which is robust to noises and dissipation. However, it is limited by sufficiently slow evolution. Here, we experimentally demonstrate the transitionless quantum driving (TLQD) of the shortcuts to adiabaticity in gate-defined semiconductor quantum dots (QDs) to greatly accelerate the conventional adiabatic passage for the first time. For a given efficiency of quantum state transfer, the acceleration can be more than twofold. The dynamic properties also prove that the TLQD can guarantee fast and high-fidelity quantum state transfer. In order to compensate for the diabatic errors caused by dephasing noises, the modified TLQD is proposed and demonstrated in experiment by enlarging the width of the counterdiabatic drivings. The benchmarking shows that the state transfer fidelity of 97.8% can be achieved. This work will greatly promote researches and applications about quantum simulations and adiabatic quantum computation based on the gate-defined QDs.

Removing Gas from a Closed-End Small Hole by Irradiating Acoustic Waves with Two Frequencies.

Filling microstructures in the air with liquid or removing trapped gases from a surface in a liquid are required in processes such as cleaning, bonding, and painting. However, it is difficult to deform the gas-liquid interface to fill a small hole with liquid when surface tension has closed one end. Therefore, it is necessary to have an efficient method of removing gas from closed-end holes in liquids. Here, we demonstrate the gas-removing method using acoustic waves from small holes. We observed gas column oscillation by changing the hole size, wettability, and liquid surface tension to clarify the mechanism. First, we found that combining two different frequencies enabled complete gas removal in water within 2 s. From high-speed observation, about half of the removal was dominated by droplet or film formation caused by oscillating the gas column. The other half was dominated by approaching and coalescing the divided gas column. We conclude that the natural frequency of both the air column and the bubbles inside the tube are important.

A comparison between the femoral neck system and other implants for elderly patients with femoral neck fracture: A preliminary report of a newly developed implant.

BACKGROUND: Femoral neck system (FNS) is an implant for patients with femoral neck fracture. It has superior angular and rotatory stability; it is less invasive because of its established locking plate system. To the best of our knowledge, there are no studies yet concerning the clinical outcomes of elderly patients with femoral neck fracture who have been treated using the FNS. METHODS: Data of patients with femoral neck fracture aged >65 years and who had undergone internal fixation with the FNS and other implants were retrospectively analyzed in this study. The follow-up period was a minimum of six months between January 2006 and November 2020. In total, 52 patients were included in the clinical evaluations, using the FNS (group F) was 25 and using other implants (group O) was 27. Outcome measurements were surgical time, the amount of blood loss, union rate and the cases that underwent reoperation. RESULTS: The average surgical time in the group F was 42 ± 13 min (range: 26-83 min) and was shorter than that in the group O (53 ± 21 min, range: 13-111 min, P = 0.032). The average blood loss in the group F was calculated to 36 ± 25 g (range: 0-91 g), while it was 41 ± 40 g (range: 0-169 g) in group O. No significant difference among the groups. The union rate of the group F was 100%, and the reoperation rate of the group F was significantly less than that of the group O (0% vs 22%, P = 0.023). CONCLUSION: Internal fixation using the FNS can be an alternative option with shorter surgical time and lower reoperation rate for elderly patients with femoral neck fracture.

Medial Meniscal Ramp Lesion Repair Concomitant With Anterior Cruciate Ligament Reconstruction Did Not Contribute to Better Anterior Knee Stability and Structural Properties After Cyclic Loading: A Porcine Model.

PURPOSE: To investigate the biomechanical efficacy of medial meniscal ramp lesion (MMRL) repair in anterior cruciate ligament (ACL) reconstruction regarding the graft protection effect after cyclic loading. METHODS: Specimens were randomized into 2 groups: (1) ACL reconstruction with unaddressed MMRL (Group U; n = 10), and (2) ACL reconstruction with repaired MMRL (Group R; n = 12). The specimens were tested cyclically (2,000 cycles, 0-40 N, 100 mm/min) in the direction of the native ACL and loaded to failure (100 mm/min) on a tensile tester. Statistically significant differences between the structural properties (length changes and anterior translations at the 100th, 500th, 1,000th, 1,500th, and 2,000th cycles, upper yield load, maximum load, linear stiffness, and elongation at failure) under cyclic loading and single-cycle loading were analyzed. RESULTS: There were no significant differences in length changes and anterior translations at the 100th, 500th, 1,000th, 1,500th, and 2,000th cycles. There were no significant differences in upper yield load (82.4 ± 31.2 N in Group U, 90.0 ± 38.5 N in Group R, P = .62), maximum load (109.9 ± 28.6 N in Group U, 124.0 ± 56.4 N in Group R, P = .48), linear stiffness (12.1 ± 4.7N/mm in Group U, 12.5 ± 4.3 N/mm in Group R, P = .84), or elongation at failure (13.5 ± 7.3 mm in Group U, 16.6 ± 7.5 mm in Group R, P = .30). CONCLUSIONS: Simultaneous MMRL repair at the time of ACL reconstruction did not decrease length changes and anterior translations during cyclic loading. In addition, simultaneous MMRL repair at the time of ACL reconstruction did not contribute to better postoperative structural properties. CLINICAL RELEVANCE: Simultaneous MMRL repair at the time of ACL reconstruction does not show a graft protective effect after cyclic loading. Graft elongation may occur during early rehabilitation.

Maturational Characterization of Mouse Cortical Neurons Three-Dimensionally Cultured in Functional Polymer FP001-Containing Medium.

The aim of the present study is to construct and characterize a novel three-dimensional culture system for mouse neurons using the functional polymer, FP001. Stereoscopically extended neurites were found in primary mouse cortical neurons cultured in the FP001-containing medium. Neurons cultured with FP001 were distributed throughout the medium of the observation range whereas neurons cultured without FP001 were distributed only on the bottom of the dish. These results demonstrated that neurons can be three-dimensionally cultured using the FP001-containing medium. The mRNA expression of the glutamatergic neuronal marker vesicular glutamate transporter 1 in neurons cultured in the FP001-containing medium were higher than that in neurons cultured in the FP001-free medium. Expression of the matured neuronal marker, microtubule-associated protein 2 (MAP2) a,b, and the synapse formation marker, Synapsin I, in neurons cultured with FP001 was also higher than that in neurons cultured without FP001. The expression pattern of MAP2a,b in neurons cultured with FP001, but not that in neurons cultured without FP001, was similar to that in the embryonic cerebral cortex. Exposure to glutamate significantly increased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction activity in neurons cultured with FP001 compared to that in neurons cultured without FP001. These results suggested that glutamatergic neurotransmission in neurons three-dimensionally cultured in the FP001-containing medium may be upregulated compared to neurons two-dimensionally cultured in the FP001-free medium. Thus, neurons with the properties close to those in the embryonic brain could be obtained by three-dimensionally culturing neurons using FP001, compared to two-dimensional culture with a conventional adhesion method.

In Vitro Reconstruction of Xenopus Oocyte Ovulation.

Progesterone is widely used to induce maturation of isolated fully grown oocytes of the African clawed frog, Xenopus laevis. However, the hormone fails to release oocytes from the layer of surrounding follicle cells. Here, we report that maturation and follicle rupture can be recapitulated in vitro by treating isolated follicular oocytes with progesterone and low doses of the matrix metalloproteinase (MMP), collagenase, which are ineffective in the absence of the steroid. Using this in vitro ovulation model, we demonstrate that germinal vesicle breakdown (GVBD) and oocyte liberation from ovarian follicles occur synchronously during ovulation. Inhibition of the MAPK pathway in these experimental settings suppresses both GVBD and follicular rupture, whereas inhibition of MMP activity delays follicular rupture without affecting GVBD. These results highlight importance of MAPK and MMP activities in the ovulation process and provide the first evidence for their involvement in the release of oocytes from ovarian follicles in frogs. The in vitro ovulation model developed in our study can be employed for further dissection of ovulation.

Interleukin-24 Transduction Modulates Human Prostate Cancer Malignancy Mediated by Regulation of Anchorage Dependence.

BACKGROUND: Hormone therapy and chemotherapy are not effective for castrate-resistant prostate cancer, thus development of novel treatment strategies is required. Gene therapy involving transient high-copy transfection of interleukin (IL)-24 with an adenoviral vector can exert antitumor activity; however, the effects of stable IL-24 transfection are not fully understood. The aim of this study was to investigate the effects of IL-24 overexpression in prostate cancer cells, in vitro. MATERIALS AND METHODS: DU145 cells were transfected the IL-24 gene using a retroviral vector. Apoptosis induction was investigated by the cell death detection ELISA, and the gene expression was analyzed by real time RT-PCR. RESULTS: IL-24 transduction suppressed the growth of prostate cancer and induced tumor cell apoptosis. In addition, up-regulation of epithelial markers and down-regulation of mesenchymal markers were noted, suggesting that tumor aggressiveness was reduced. CONCLUSION: Introduction of IL-24 displays antitumor activity both by induction of apoptosis and regulation of anchorage dependence.

Tandem repeats of the 5' flanking region of human MUC5AC have a role as a novel enhancer in MUC5AC gene expression.

MUC5AC is a well-known gastric differentiation marker, which has been frequently used for the classification of stomach cancer. However, the molecular mechanism of regulation of MUC5AC expression remains to be elucidated. In previous studies, we have shown that Gli regulated MUC5AC transcription through the Gli-binding motif in the 5' region of MUC5AC. Gli played important roles, but independently was not sufficient for MUC5AC expression. In this study, we analyzed a 4010 bp fragment of the 5'-flanking promoter region of the human MUC5AC gene by luciferase assay, and found a novel distal enhancer region located between -1434 bp to -3000 bp upstream from the first ATG initiation codon. This region is composed of repetitive DNA sequences 5'-TCACTCAC-3'. The strength of enhancer activities depended on the length of the repetitive region. The tandem repeats are conserved among primates, but not in other mammals. The tandem repeat regions enhanced promoter activities not only of MUC5AC but also of other genes. The enhancer effect of the tandem repeat regions was maintained even when inverted. ChIP analysis revealed that H3K9me3 binds to the tandem repeat regions. Together, our results suggest that the tandem repeat region in the MUC5AC promoter has the potential to act as a strong enhancer, and H3K9me3 may contribute to histone modifications of this region.

Gastroesophageal Reflux Disease-Related Disorders of Systemic Sclerosis Based on the Analysis of 66 Patients.

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD)-related disorders of systemic sclerosis (SSc) patients have not been adequately investigated. METHODS: Sixty-six SSc patients (5 males and 61 females; 56.6 ± 14.6 years old) who underwent esophagogastroduodenoscopy were analyzed on the basis of 16 background factors. They were additionally compared with 116 matched non-SSc subjects controlling age, sex, and use of proton pump inhibitors (PPIs). RESULTS: The mean disease duration of 66 patients was 5.1 ± 8.1 years, and their breakdown was as follows: 53 (80.3%) with GERD, 38 (57.6%) with GERD-related symptoms, and 20 (30.3%) with reflux esophagitis (RE; LA-A: 10, LA-B: 5, LA-C: 4, LA-D: 1). Use of PPI (p = 0.0455), complication of interstitial lung disease (p = 0.0242), and history of cyclophosphamide therapy (p = 0.0184) denoted significant association with GERD-related symptoms. Older age (p = 0.0211) was significantly associated with RE. None of GERD-related disorders showed any difference between 37 diffuse cutaneous SSc and 29 limited cutaneous SSc patients. The matched analysis indicated that SSc patients had higher prevalence of GERD (p < 0.0001), GERD-related symptoms (p = 0.0034), and RE (p = 0.0002). CONCLUSION: SSc patients tend to have worse GERD symptoms and severer RE. However, most SSc-associated factors did not show significant association with GERD-related disorders, indicating the difficulty in predicting GERD-related disorders among SSc patients.

Pool-based genome-wide association study identified novel candidate regions on BTA9 and 14 for oleic acid percentage in Japanese Black cattle.

Fatty acid composition is an important indicator of beef quality. The objective of this study was to search the potential candidate region for fatty acid composition. We performed pool-based genome-wide association studies (GWAS) for oleic acid percentage (C18:1) in a Japanese Black cattle population from the Hyogo prefecture. GWAS analysis revealed two novel candidate regions on BTA9 and BTA14. The most significant single nucleotide polymorphisms (SNPs) in each region were genotyped in a population (n = 899) to verify their effect on C18:1. Statistical analysis revealed that both SNPs were significantly associated with C18:1 (p = .0080 and .0003), validating the quantitative trait loci (QTLs) detected in GWAS. We subsequently selected VNN1 and LYPLA1 genes as candidate genes from each region on BTA9 and BTA14, respectively. We sequenced full-length coding sequence (CDS) of these genes in eight individuals and identified a nonsynonymous SNP T66M on VNN1 gene as a putative candidate polymorphism. The polymorphism was also significantly associated with C18:1, but the p value (p = .0162) was higher than the most significant SNP on BTA9, suggesting that it would not be responsible for the QTL. Although further investigation will be needed to determine the responsible gene and polymorphism, our findings would contribute to development of selective markers for fatty acid composition in the Japanese Black cattle of Hyogo.

A New Cell Separation Method Based on Antibody-Immobilized Nanoneedle Arrays for the Detection of Intracellular Markers.

Focusing on intracellular targets, we propose a new cell separation technique based on a nanoneedle array (NNA) device, which allows simultaneous insertion of multiple needles into multiple cells. The device is designed to target and lift ("fish") individual cells from a mixed population of cells on a substrate using an antibody-functionalized NNA. The mechanics underlying this approach were validated by force analysis using an atomic force microscope. Accurate high-throughput separation was achieved using one-to-one contacts between the nanoneedles and the cells by preparing a single-cell array in which the positions of the cells were aligned with 10,000 nanoneedles in the NNA. Cell-type-specific separation was realized by controlling the adhesion force so that the cells could be detached in cell-type-independent manner. Separation of nestin-expressing neural stem cells (NSCs) derived from human induced pluripotent stem cells (hiPSCs) was demonstrated using the proposed technology, and successful differentiation to neuronal cells was confirmed.

Web application for genetic modification flux with database to estimate metabolic fluxes of genetic mutants.

Computational analysis of metabolic fluxes is essential in understanding the structure and function of a metabolic network and in rationally designing genetically modified mutants for an engineering purpose. We had presented the genetic modification flux (GMF) that predicts the flux distribution of a broad range of genetically modified mutants. To enhance the feasibility and usability of GMF, we have developed a web application with a metabolic network database to predict a flux distribution of genetically modified mutants. One hundred and twelve data sets of Escherichia coli, Corynebacterium glutamicum, Saccharomyces cerevisiae, and Chinese hamster ovary were registered as standard models.

Atrophic gastritis and enlarged gastric folds diagnosed by double-contrast upper gastrointestinal barium X-ray radiography are useful to predict future gastric cancer development based on the 3-year prospective observation.

BACKGROUND: Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is the standard gastric cancer screening method in Japan. Atrophic gastritis and enlarged gastric folds are considered the two major features of Helicobacter pylori-induced chronic gastritis, but the clinical meaning of evaluating them by UGI-XR has not been elucidated. METHODS: We analyzed healthy UGI-XR examinees without a history of gastrectomy, previous Helicobacter pylori eradication and usage of gastric acid suppressants. RESULTS AND CONCLUSIONS: Of the 6433 subjects, 1936 (30.1 %) had atrophic gastritis and 1253 (19.5 %) had enlarged gastric folds. During the 3-year prospective observational follow-up, gastric cancer developed in seven subjects, six of whom (85.7 %) had atrophic gastritis with H. pylori infection and five of whom (71.4 %) had enlarged gastric folds with H. pylori infection. The Kaplan-Meier method with log-rank testing revealed that both UGI-XR-based atrophic gastritis (p = 0.0011) and enlarged gastric folds (p = 0.0003) are significant predictors for future gastric cancer incidence.