Two cases of respiratory infection due to Pasteurella multocida: Acute and chronic form.

We present two cases of Pasteurella multocida (P. multocida) respiratory infection. The first case involves a 62-year-old female with abnormal chest shadows, a history of bronchial asthma, and colorectal cancer. Endobronchial ultrasound with a guide sheath (EBUS-GS) revealed granulomatous changes, and P. multocida was cultured. The second case is a 64-year-old female presenting to the emergency department with progressively worsening chest pain and dyspnea, with P. multocida detected from her sputum culture. Treatment with penicillin antibiotics resulted in symptom improvement and normalization of CT findings. These cases indicate the importance of considering P. multocida in respiratory infections, given the patients' history of pet ownership and the nonspecific imaging findings and symptoms. This highlights the necessity for accurate diagnosis and appropriate antibiotic treatment, particularly in cases where animal traumatic exposure is not detected.

The liver-to-spleen ratio is a risk factor predicting oxygen demand in COVID-19 patients.

Background: We aimed to investigate risk factors predicting oxygen demand in COVID-19 patients. Methods: Patients admitted to Shizuoka General Hospital with COVID-19 from August 2020 to August 2021 were included. First, we divided patients into groups with and without oxygen demand. Then, we compared patients' clinical characteristics and laboratory and radiological findings to determine factors predicting oxygen demand. Results: One hundred seventy patients with COVID-19 (aged 58±15 years, 57 females) were enrolled. Common comorbidities were cardiovascular diseases (47.6%), diabetes mellitus (28.8%), and dyslipidemia (26.5%). Elder age, higher body mass index, cardiovascular diseases, diabetes mellitus, lower lymphocyte count, albumin, hepatic attenuation value, and the liver-to-spleen ratio (L/S), higher D-dimer, aspartate aminotransferase, lactate dehydrogenase, troponin-T, C-reactive protein, KL-6, chest and abdominal circumference, and visceral fat were found in patients with oxygen demand. According to the multivariate logistic regression analysis, L/S, lymphocyte count, D-dimer, and abdominal circumference under the diaphragm were independent risk factors predicting oxygen demand in COVID-19 patients. Conclusions: On admission, L/S, lymphocyte count, D-dimer, and abdominal circumference were predictive factors for oxygen demand. These factors may help in the appropriate triage of COVID-19 patients in the decision to admit them to the hospital.

Privacy-Preserving Statistical Analysis of Genomic Data Using Compressive Mechanism with Haar Wavelet Transform.

To promote the use of personal genome information in medicine, it is important to analyze the relationship between diseases and the human genomes. Therefore, statistical analysis using genomic data is often conducted, but there is a privacy concern with respect to releasing the statistics as they are. Existing methods to address this problem using the concept of differential privacy cannot provide accurate outputs under strong privacy guarantees, making them less practical. In this study, for the first time, we investigate the application of a compressive mechanism to genomic statistical data and propose two approaches. The first is to apply the normal compressive mechanism to the statistics vector along with an algorithm to determine the number of nonzero entries in a sparse representation. The second is to alter the mechanism based on the data, aiming to release significant single nucleotide polymorphisms with a high probability. In this algorithm, we apply the compressive mechanism with the input as a sparse vector for significant data and the Laplace mechanism for nonsignificant data. By using the Haar wavelet transform for the compressive mechanism, we can determine the number of nonzero elements and the amount of noise. In addition, we give theoretical guarantees that our proposed methods achieve ϵ-differential privacy. We evaluated our methods in terms of accuracy and rank error compared with the Laplace and exponential mechanisms. The results show that our second method in particular can guarantee high privacy assurance as well as utility.

Electron-Deficient Benzo[de]isoquinolino[1,8-gh]quinoline Diamide π-Electron Systems.

Synthetically versatile electron-deficient π-electron systems are urgently needed for organic electronics, yet their design and synthesis are challenging due to the low reactivity from large electron affinities. In this work, we report a benzo[de]isoquinolino[1,8-gh]quinoline diamide (BQQDA) π-electron system. The electron-rich condensed amide as opposed to the generally-employed imide provides a suitable electronic feature for chemical versatility to tailor the BQQDA π-electron system for various electronic applications. We demonstrate an effective synthetic method to furnish the target BQQDA parent structure, and highly selective functionalization can be performed on bay positions of the π-skeleton. In addition, thionation of BQQDA can be accomplished under mild conditions. Fine-tuning of fundamental properties and supramolecular packing motifs are achieved via chemical modifications, and the cyanated BQQDA organic semiconductor demonstrates a high air-stable electron-carrier mobility.

Blood eosinophil count and FeNO to predict benralizumab effectiveness in real-life severe asthma patients.

OBJECTIVE: Benralizumab is a promising drug for severe uncontrolled asthma. This study aimed to clarify the effectiveness of benralizumab in a real-life setting. METHODS: Subjects included 24 patients with severe type 2 asthma who received benralizumab between April 2018 and July 2019. Changes in parameters, exacerbation frequency, and oral corticosteroid (OCS) use after 4 and 24 weeks of administration were examined. The parameters included the Global Evaluation of Treatment Effectiveness (GETE) scale, Asthma Control Questionnaire (ACQ), Asthma Control Test (ACT), blood eosinophils, fractional exhaled nitric oxide (FeNO), and spirometry. The response to treatment was defined as follows: for patients with exacerbations or OCS use before treatment initiation, a reduction of ≥50% in exacerbation frequency or OCS use; and for patients without exacerbations or OCS use, an improvement of ≥0.5 in ACQ scores and ≥3 in ACT scores, or of ≥10.38% in FEV1. RESULTS: Twenty-one patients completed the treatment for 24 weeks. Excellent and good GETE scales and ACQ and ACT improvement were found in 67% of the patients at 4 weeks, and the effect continued until 24 weeks. The patients' rate with exacerbations was significantly reduced compared to the previous 24 weeks before administration. In 17 patients receiving OCS, the use could be reduced or quit in 14 patients. Overall, 16 patients (76.2%) met the responder definition and could be predicted by the baseline eosinophil count and FeNO levels with the best cutoff values of 100/µL and 40 ppb, respectively. CONCLUSIONS: Blood eosinophil and FeNO could predict benralizumab effectiveness.

Efficient Differentially Private Methods for a Transmission Disequilibrium Test in Genome Wide Association Studies.

To achieve the provision of personalized medicine, it is very important to investigate the relationship between diseases and human genomes. For this purpose, large-scale genetic studies such as genome-wide association studies are often conducted, but there is a risk of identifying individuals if the statistics are released as they are. In this study, we propose new efficient differentially private methods for a transmission disequilibrium test, which is a family-based association test. Existing methods are computationally intensive and take a long time even for a small cohort. Moreover, for approximation methods, sensitivity of the obtained values is not guaranteed. We present an exact algorithm with a time complexity of 𝒪(nm) for a dataset containing n families and m single nucleotide polymorphisms (SNPs). We also propose an approximation algorithm that is faster than the exact one and prove that the obtained scores' sensitivity is 1. From our experimental results, we demonstrate that our exact algorithm is 10, 000 times faster than existing methods for a small cohort with 5, 000 SNPs. The results also indicate that the proposed method is the first in the world that can be applied to a large cohort, such as those with 106 SNPs. In addition, we examine a suitable dataset to apply our approximation algorithm. Supplementary materials are available at https://github.com/ay0408/DP-trio-TDT.

Effectiveness of a 23-valent pneumococcal polysaccharide vaccine for the prevention of pneumococcal pneumonia in the elderly with chronic respiratory diseases: a case-control study of a single center.

BACKGROUND: The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in preventing pneumococcal pneumonia has been controversial. METHODS: To evaluate the effectiveness of the PPSV23 in elderly outpatients with chronic respiratory diseases, we carried out a case-control study, including 4128 outpatients aged ≥ 65 years, in the respiratory department. RESULTS: There were 320 vaccinated patients, of which 164 were diagnosed with pneumococcal pneumonia. The adjusted odds ratio was 0.39 (95% confidence interval (CI), 0.17 to 0.89). In the subsets consisting of age groups ≥ 70 and ≥ 75 years, the adjusted odds ratio (95% CI) was respectively 0.16 (0.04 to 0.67) and 0.15 (0.02 to 1.12). CONCLUSION: This real-world study suggests that PPSV23 can be useful in preventing pneumococcal pneumonia in the elderly with chronic respiratory diseases.

More practical differentially private publication of key statistics in GWAS.

Motivation: Analyses of datasets that contain personal genomic information are very important for revealing associations between diseases and genomes. Genome-wide association studies, which are large-scale genetic statistical analyses, often involve tests with contingency tables. However, if the statistics obtained by these tests are made public as they are, sensitive information of individuals could be leaked. Existing studies have proposed privacy-preserving methods for statistics in the χ2 test with a 3 × 2 contingency table, but they do not cover all the tests used in association studies. In addition, existing methods for releasing differentially private P-values are not practical. Results: In this work, we propose methods for releasing statistics in the χ2 test, the Fisher's exact test and the Cochran-Armitage's trend test while preserving both personal privacy and utility. Our methods for releasing P-values are the first to achieve practicality under the concept of differential privacy by considering their base 10 logarithms. We make theoretical guarantees by showing the sensitivity of the above statistics. From our experimental results, we evaluate the utility of the proposed methods and show appropriate thresholds with high accuracy for using the private statistics in actual tests. Availability and implementation: A python implementation of our experiments is available at https://github.com/ay0408/DP-statistics-GWAS. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Oscillometry as a Predictor of Exercise Tolerance in COPD.

The usefulness of the oscillometry, known as forced oscillation technique, for predicting exercise tolerance in subjects with COPD is unknown. To test the hypothesis, we investigated whether oscillometry could predict a 6-minute walking distance (6MWD) <350 m in the 6-minute walk test (6MWT).This was a prospective, observational study. Fifty-seven subjects with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between April 2015 and April 2016 (54 males; median age, 70 years; and %FEV1, 61.0%). Modified MRC dyspnea scale (mMRC), COPD Assessment Test (CAT), oscillometry, spirometry, and 6MWT were performed in a stable condition. The participants were classified into subjects with 6MWD ≥350 m or 6MWD <350 m, and the predictor of 6MWD <350 m was assessed.Of the 57 total subjects, 43 (75.4%) had a 6MWD ≥350 m, and 14 (24.6%) had a 6MWD <350 m. Between the two groups, there were significant differences in mMRC scale, GOLD stages, CAT scores, FEV1, IC, 6MWD, lowest SpO2, maximum Borg scale, respiratory resistance (Rrs), and reactance (Xrs). In multivariate regression analysis, a 6MWD <350 m was independently predicted by CAT scores (OR 1.15, 95% CI: 1.01-1.30) and inspiratory R5 (OR 6.01, 95% CI: 1.09-33.30). In receiver operating characteristic curves, the area under the curve was 0.76, 0.78, and 0.85 for CAT scores, R5, and CAT scores + R5, respectively, with the best cutoff value of 17 and 2.82 cmH20/L/s. In conclusion, the oscillatory parameter, inspiratory R5, predicted low exercise tolerance in COPD subjects.

Hybrid Rubisco with Complete Replacement of Rice Rubisco Small Subunits by Sorghum Counterparts Confers C4 Plant-like High Catalytic Activity.

Photosynthetic rate at the present atmospheric condition is limited by the CO2-fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) because of its extremely low catalytic rate (kcat) and poor affinity for CO2 (Kc) and specificity for CO2 (Sc/o). Rubisco in C4 plants generally shows higher kcat than that in C3 plants. Rubisco consists of eight large subunits and eight small subunits (RbcS). Previously, the chimeric incorporation of sorghum C4-type RbcS significantly increased the kcat of Rubisco in a C3 plant, rice. In this study, we knocked out rice RbcS multigene family using the CRISPR-Cas9 technology and completely replaced rice RbcS with sorghum RbcS in rice Rubisco. Obtained hybrid Rubisco showed almost C4 plant-like catalytic properties, i.e., higher kcat, higher Kc, and lower Sc/o. Transgenic lines expressing the hybrid Rubisco accumulated reduced levels of Rubisco, whereas they showed slightly but significantly higher photosynthetic capacity and similar biomass production under high CO2 condition compared with wild-type rice. High-resolution crystal structural analysis of the wild-type Rubisco and hybrid Rubisco revealed the structural differences around the central pore of Rubisco and the ßC-ßD hairpin in RbcS. We propose that such differences, particularly in the ßC-ßD hairpin, may impact the flexibility of Rubisco catalytic site and change its catalytic properties.

Cholesterol-binding protein TSPO2 coordinates maturation and proliferation of terminally differentiating erythroblasts.

TSPO2 (translocator protein 2) is a transmembrane protein specifically expressed in late erythroblasts and has been postulated to mediate intracellular redistribution of cholesterol. We identified TSPO2 as the causative gene for the HK (high-K+) trait with immature red cell phenotypes in dogs and investigated the effects of the TSPO2 defects on erythropoiesis in HK dogs with the TSPO2 mutation and Tspo2 knockout (Tspo2-/-) mouse models. Bone marrow-derived erythroblasts from HK dogs showed increased binucleated and apoptotic cells at various stages of maturation and shed large nuclei with incomplete condensation when cultured in the presence of erythropoietin, indicating impaired maturation and cytokinesis. The canine TSPO2 induces cholesterol accumulation in the endoplasmic reticulum and could thereby regulate cholesterol availability by changing intracellular cholesterol distribution in erythroblasts. Tspo2-/- mice consistently showed impaired cytokinesis with increased binucleated erythroblasts, resulting in compensated anemia, and their red cell membranes had increased Na,K-ATPase, resembling the HK phenotype in dogs. Tspo2-deficient mouse embryonic stem cell-derived erythroid progenitor (MEDEP) cells exhibited similar morphological defects associated with a cell-cycle arrest at the G2/M phase, resulting in decreased cell proliferation and had a depletion in intracellular unesterified and esterified cholesterol. When the terminal maturation was induced, Tspo2-/- MEDEP cells showed delays in hemoglobinization; maturation-associated phenotypic changes in CD44, CD71, and TER119 expression; and cell-cycle progression. Taken together, these findings imply that TSPO2 is essential for coordination of maturation and proliferation of erythroblasts during normal erythropoiesis.

Improved cough- and sputum-related quality of life after initiation of treatment in pulmonary tuberculosis.

BACKGROUND: Cough and sputum are the major symptoms of pulmonary tuberculosis (TB). However, the relationship between these symptoms and treatment for TB is not fully understood. The aim of this prospective study was to clarify the cough- and sputum-related quality of life (QOL) in patients with pulmonary TB before and after initiation of treatment. METHODS: The study included 85 patients with active pulmonary TB who were hospitalized from July 2014 to August 2015. They completed the Leicester Cough Questionnaire (LCQ: range 3-21, the higher the better) and the Cough and Sputum Assessment Questionnaire (CASA-Q: range 0-100, the higher the better) on admission and at discharge after 2 months of treatment. RESULTS: The LCQ and CASA-Q scores were reduced on admission. A multivariate linear regression analysis revealed that younger age, more than two cavitary lesions, and the presence of bronchial TB were associated with reduced LCQ total score. However, each score significantly improved at discharge, regardless of the initial grade of the sputum smear, site of the lesion, number of cavitary lesions, and presence of bronchial TB. The change in the mean LCQ total score was 2.28 (95% confidence interval, 1.56-3.00). The changes in the mean CASA-Q cough symptoms, cough impact, sputum symptoms, and sputum impact scores were 22.84 (18.44-27.25), 10.96 (7.20-14.71), 17.25 (13.33-21.18), and 5.25 (2.49-8.00), respectively. CONCLUSIONS: Cough- and sputum-related QOL was impaired in patients with pulmonary TB before treatment but improved after initiation of treatment regardless of the clinical characteristics.

Efficacy and Safety of Amrubicin in Non-Small-Cell Lung Cancer Patients Beyond Third-Line Therapy.

BACKGROUND: There are no standard cytotoxic treatments for non-small-cell lung cancer (NSCLC) patients beyond third-line therapy. The purpose of this study was to evaluate the efficacy and safety of amrubicin in pretreated NSCLC patients. METHODS: The records of NSCLC patients who received amrubicin monotherapy as a third or later line of chemotherapy at Shizuoka General Hospital between April 2007 and March 2015 were retrospectively reviewed. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 3.0. RESULTS: Overall, 69 patients were enrolled in this study; 16 patients were female and the median age was 67 years. The median number of treatment cycles was 3. The response rate was 7.2%, and the disease control rate was 63.8%. The median progression-free survival was 2.8 months. The median overall survival was 7.7 months. Hematological toxicities of ≥ grade 3 included leukopenia (59.4%) and neutropenia (62.3%). Non-hematological toxicities of ≥ grade 2 included anorexia (27.5%) and fatigue (24.6%). CONCLUSION: Although hematological toxicities were severe, these results suggested that amrubicin in NSCLC patients beyond third-line therapy shows sufficient clinical benefit.

Photoinduced Electron Transfer-Regulated Protein Labeling With a Coumarin-Based Multifunctional Photocrosslinker.

We developed a novel diazirine-based photolabeling agent having a (coumarin-4-yl)methyl ester scaffold, which exhibited multiple photochemical properties of crosslinking, fluorogenicity and cleavage. These properties can be kinetically regulated via photoinduced electron transfer between diazirine and coumarin moieties. The C-O bond of (coumarin-4-yl)methyl ester can be cleaved via photochemical excitation of coumarin moiety, that function has been initially quenched by the diazirine moiety. Upon diazirine photolysis with 365-nm light, interacting protein was stably captured with photoactivatable ligand probe. Then, the unlocked cleavage function was activated with 313 nm light, and the reaction was accelerated in a weakly-basic solution. The crosslinked protein could be selectively isolated with attachment of a small coumarin tag on the surface. This multi-functional labeling agent has a great potential to facilitate LC-MS/MS-based protein identification.

Zigzag-Elongated Fused π-Electronic Core: A Molecular Design Strategy to Maximize Charge-Carrier Mobility.

Printed and flexible electronics requires solution-processable organic semiconductors with a carrier mobility (µ) of ≈10 cm2 V-1 s-1 as well as high chemical and thermal durability. In this study, chryseno[2,1-b:8,7-b']dithiophene (ChDT) and its derivatives, which have a zigzag-elongated fused π-electronic core (π-core) and a peculiar highest occupied molecular orbital (HOMO) configuration, are reported as materials with conceptually new semiconducting π-cores. ChDT and its derivatives are prepared by a versatile synthetic procedure. A comprehensive investigation reveals that the ChDT π-core exhibits increasing structural stability in the bulk crystal phase, and that it is unaffected by a variation of the transfer integral, induced by the perpetual molecular motion of organic materials owing to the combination of its molecular shape and its particular HOMO configuration. Notably, ChDT derivatives exhibit excellent chemical and thermal stability, high charge-carrier mobility under ambient conditions (µ ≤ 10 cm2 V-1 s-1), and a crystal phase that is highly stable, even at temperatures above 250 °C.

Forced oscillation technique as a predictor of FEV1 improvement in asthma.

The usefulness of the forced oscillation technique (FOT) for predicting the treatment outcomes in untreated asthmatic patients is unknown. We investigated whether FOT could predict an improvement in FEV1 following treatment. FOT, spirometry, and fractional exhaled nitric oxide were performed in 31 outpatients before and after undergoing a minimum of two months combination therapy of inhaled corticosteroids and long-acting ß2-agonists. The patients were classified as responders or nonresponders to treatment based on the presence or absence of a 10% improvement in the FEV1. The responders to the treatment regimen exhibited lower FEV1, FEV1/FVC, FEF25-75%, and higher respiratory resistance at 5Hz (R5), as well as a difference between R5 and R20 (R5-R20) at baseline compared to the nonresponders. In the multivariate logistic regression analyses, a change in FEV1 greater than 10% was independently predicted by the R5 (adjusted odds ratio: 15.9). The ROC curve analyses revealed that the area under the curve for R5 (0.731) was larger than that of the other parameters. Thus, R5 is a forced oscillatory parameter and predicts an improvement in FEV1 following treatment.