Impacts of workplace verbal aggression classified via text mining on workers' mental health.

BACKGROUND: Exposure to workplace aggression adversely affects workers' health; however, little is known regarding the impact of specific types of verbal content. AIMS: We aimed to examine the relationship between exposure to several types of aggressive words at work and the victim's depressive symptoms and sleep disturbance using text mining. METHODS: We conducted a longitudinal survey with 800 workers in wholesale and retail companies; of which, 500 responded to the follow-up survey. The Centre for Epidemiologic Studies-Depression Scale and Pittsburgh Sleep Quality Index were filled out by the participants, and their responses were analysed by logistic regression to evaluate the risk of depression or sleep problems. We collected exact aggressive words encountered at work over the past year as a dependent variable and classified it into four types using text mining, such as words criticizing one's performance. RESULTS: The follow-up rate was 63%. Exposure to words threatening one's life showed a significant relationship with the risk of depression (odds ratio [OR] = 13.94, 95% confidence interval [CI] = 1.76-110.56). The exposure to words criticizing one's job performance is significantly related to the risk of sleep disturbance (OR = 5.56, 95% CI = 2.08-14.88). CONCLUSIONS: These findings suggest that different contents of verbal aggression can have different impacts on workers' health. This indicates that not only overtly threatening and abusive language but also words related to one's performance can be a risk factor for workers, depending on how they are delivered. To mitigate the adverse effects, promoting effective communication and cultivating psychological detachment from work may be beneficial.

Clinical and Surgical Outcomes of Endoscopic Endonasal Approach for Giant Pituitary Adenomas: Analysis of Predictive Factors.

BACKGROUND: Giant pituitary adenomas (GPAs) are defined as tumors with ≥40 mm in any maximum diameter, and these tend to invade multiple intracranial compartments. Hence, treatment remains a surgical challenge. OBJECTIVE: To describe the clinical and surgical outcomes of the endoscopic endonasal approach (EEA) for GPA in a pituitary referral center in Latin America and to analyze associated predictive factors. METHODS: 37 patients with histologically-confirmed GPA treated solely through the EEA between a 2-year period were included. Preoperative and postoperative clinical and neuroimaging findings; surgical morbidity and mortality; and binary logistic regression analysis to assess predictive factors were analyzed. RESULTS: Preoperative visual impairment prevalence was 97.3%. Mean tumor volume was 32 cc and gross total resection rate was 40.5%. Favorable visual acuity and visual fields outcome rate was 75% and 82.9%, respectively. In the multivariate analysis, bilateral cavernous sinus invasion (P = 0.018) and postoperative cerebrospinal fluid (CSF) leak (P = 0.036) were associated with an unfavorable visual acuity outcome, while radiation therapy (P = 0.035) was for visual fields. Similarly, intraoperative CSF leak was a predictive factor for postoperative CSF leak (10.8%) (P = 0.042) and vascular injury (13.5%) (P = 0.048). CONCLUSIONS: In this first Mexican clinical series, we demonstrated that the EEA is a safe and effective technique for GPA, although early diagnosis and prompt intervention may promote further visual function preservation without significant endocrine morbidity.

Endothelial Insulin Resistance Exacerbates Experimental Periodontitis.

Epidemiological studies suggest that the severity of periodontitis is higher in people with diabetes than in healthy individuals. Insulin resistance might play a crucial role in the pathogenesis of multiple diabetic complications and is reportedly induced in the gingiva of rodents with type 2 diabetes; however, the molecular mechanisms underlying the pathogenesis of diabetes-related periodontitis remain unclear. Therefore, we aimed to investigate whether endothelial insulin resistance in the gingiva may contribute to the pathogenesis of periodontitis as well as elucidate its underlying molecular mechanisms. We demonstrated that insulin treatment downregulated lipopolysaccharide (LPS)-induced or tumor necrosis factor α (TNFα)-induced VCAM1 expression in endothelial cells (ECs) via the PI3K/Akt activating pathway, resulting in reduced cellular adhesion between ECs and leukocytes. Hyperglycemia-induced selective insulin resistance in ECs diminished the effect of insulin on LPS- or TNFα-stimulated VCAM1 expression. Vascular endothelial cell-specific insulin receptor knockout (VEIRKO) mice exhibited selective inhibition of the PI3K/Akt pathway in the gingiva and advanced experimental periodontitis-induced alveolar bone loss via upregulation of Vcam1, Tnfα, Mcp-1, Rankl, and neutrophil migration into the gingiva compared with that in the wild-type (WT) mice despite being free from diabetes. We also observed that insulin-mediated activation of FoxO1, a downstream target of Akt, was suppressed in the gingiva of VEIRKO and high-fat diet (HFD)-fed mice, hyperglycemia-treated ECs, and primary ECs from VEIRKO. Further analysis using ECs transfected with intact and mutated FoxO1, with mutations at 3 insulin-mediated phosphorylation sites (T24A, S256D, S316A), suggested that insulin-mediated regulation of VCAM1 expression and cellular adhesion of ECs with leukocytes was attenuated by mutated FoxO1 overexpression. These results suggest that insulin resistance in ECs may contribute to the progression of periodontitis via dysregulated VCAM1 expression and cellular adhesion with leukocytes, resulting from reduced activation of the PI3K/Akt/FoxO1 axis.

Development of a radiopaque tiltmeter to improve reproducibility for Fowler's position on chest radiography.

INTRODUCTION: We have developed a novel radiopaque tiltmeter (ROT) that can indicate patient tilt during a radiography examination and display it on X-ray images. This study evaluated the effect of variation of patient tilt on the reproducibility of Fowler's position for chest radiography and the accuracy of the ROT. METHODS: We evaluated the reproducibility of Fowler's position based on changes from the first day in the central venous catheter (CVC) tip position and the cardiothoracic ratio (CTR) with and without a digital tiltmeter to verify its efficacy in patients who underwent mobile chest radiography. The ROT contains radiopaque liquid consisting of white barium sulfate solution and oil and has a scale bar of 15°-75° with increments of 15° to indicate ROT tilt. The ROT tilt was increased from 10° to 80° in increments of 10°. We then evaluated (1) the difference between the ROT tilt and the tilt measured with a digital tiltmeter, and (2) the ROT tilt displayed on the X-ray image. RESULTS: With regard to reproducibility in Fowler's position, changes in the CVC tip position were 2.8 ± 3.9 mm and 10.7 ± 10.6 mm with and without the tiltmeter, respectively (p < 0.05) and the respective rates of change in the CTR were 0.7% ± 0.6% and 4.0% ± 2.1% (p < 0.05). Differences between the ROT tilt and the tilt measured by the digital tiltmeter were within ±2.5°. All ROT tilts displayed on the X-ray images were recognized exactly as each tilt. CONCLUSION: Our novel ROT had the potential to accurately indicate patient tilt during chest radiography, which could be helpful in terms of reproducibility and precise follow-up. IMPLICATIONS FOR PRACTICE: Use of the ROT for determination of patient tilt can improve reproducibility in Fowler's position, allowing more accurate serial X-ray imaging.

A 5-kV pulse generator with a 100-kV/µs slew rate based on series-connected 1700-V SiC MOSFETs for electrical insulation tests.

This study demonstrates a high-slew-rate 5-kV pulse generator for electrical insulation tests. Electrical equipment, such as electrical actuators and traction drive motors, are exposed to severe electrical stress because recent switching inverters have high-frequency outputs with high supply voltages using wide-bandgap power devices. For an advanced electrical insulation test, a high-voltage pulse generator is required with a high slew rate; however, such generators suffer from large switching noise, followed by measurement noise, such as ground voltage fluctuations and radiation noise, hindering the detection of partial discharge (PD) phenomena. In this study, we propose a 5-kV pulse generator based on series-connected 1700-V silicon carbide (SiC) metal-oxide-semiconductor field-effect transistors (MOSFETs). Four 1700-V SiC MOSFETs are connected in series as a 5-kV SiC switching module, constituting a half-bridge configuration for the pulse generator. The obtained switching waveforms exhibit fast rise times of 48 ns under 5 kV and 6.2 ns under 400 V with a low voltage overshoot and ringing owing to superior device characteristics and reduced parasitic inductances. Because of the low switching noise, we detect a clear PD signal with a 1500-V pulse when using the fabricated pulse generator for a PD test of a twisted pair. The proposed pulse generator uses a hard switching configuration such that the pulse generator can vary the pulse width from 150 ns to DC and increase the switching pulse cycle beyond 1 MHz by changing the control signals of the SiC MOSFETs.

Absence of microsatellite instability in extramammary Paget's disease.

Background: Deficiency of DNA mismatch repair (MMR) induces microsatellite instability (MSI). Pembrolizumab, an antibody targeting PD-1 (an immune checkpoint inhibitor), is more effective against MMR-deficient tumours than against MMR-proficient tumours. The status of MMR is a useful biomarker for predicting the effectiveness of pembrolizumab administration. Although the status of MMR has attracted attention in skin tumours, there are few reports on MSI in extramammary Paget's disease (EMPD). Objectives: To evaluate the status of MMR in patients with EMPD. Materials & Methods: One hundred one patients with EMPD were included. MMR status of the genomic DNA of each subject was analysed using Promega panel (approved as a companion diagnostic agent for the administration of pembrolizumab). Results: MSI testing showed the occurrence rates of MSI-high (more than two markers are unstable), MSI-low (one marker is unstable) and MSS (all markers are stable) tumour tissues were 0% (0/101), 1.0% (1/101) and 99.0% (100/101), respectively. Conclusion: The status of MMR may not be useful for the potential therapeutic application of pembrolizumab.

Relative contributions of large-scale and wedgelet currents in the substorm current wedge.

We examined how much large-scale and localized upward and downward currents contribute to the substorm current wedge (SCW), and how they evolve over time, using the THEMIS all-sky imagers (ASIs) and ground magnetometers. One type of events is dominated by a single large-scale wedge, with upward currents over the surge and broad downward currents poleward-eastward of the surge. The other type of events is a composite of large-scale wedge and wedgelets associated with streamers, with each wedgelet having comparable intensity to the large-scale wedge currents. Among 17 auroral substorms with wide ASI coverage, the composite current type is more frequent than the single large-scale wedge type. The dawn-dusk size of each wedgelet is ~ 600 km in the ionosphere (~ 3.2 R E in the magnetotail, comparable to the flow channel size). We suggest that substorms have more than one type of SCW, and the composite current type is more frequent.

A case of resected retroperitoneal metachronous solitary metastasis from caecal cancer.

Colorectal cancer metastasis to the retroperitoneum, especially solitary metastasis allowing curative resection, is rare. We report a case of complete resection of retroperitoneal metachronous solitary metastasis from caecal cancer without distant metastasis. An 80-year-old woman with caecal cancer underwent laparoscopic ileocaecal resection with regional lymph node dissection. According to the eighth edition of the TNM classification, the pathological diagnosis was stage IIA (T3N0M0). Six months following the surgery, computed tomography revealed a solitary mass of 2cm diameter, dorsal to the right kidney. A second procedure for the removal of the tumour was performed. The lesion was pathologically diagnosed as a metachronous solitary retroperitoneal metastasis from caecal cancer. The patient is surviving and free from recurrence 17 months following the second procedure.

mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse.

The mechanism by which the cytosolic protein Zap70 physically interacts with and phosphorylates its substrate, the transmembrane protein LAT, upon T cell receptor (TCR) stimulation remains largely obscure. In this study, we found that the pharmacological inhibition of formins, a major class of actin nucleators, suppressed LAT phosphorylation by Zap70, despite TCR stimulation-dependent phosphorylation of Zap70 remaining intact. High-resolution imaging and three-dimensional image reconstruction revealed that localization of phosphorylated Zap70 to the immune synapse (IS) and subsequent LAT phosphorylation are critically dependent on formin-mediated actin polymerization. Using knockout mice, we identify mDia1 and mDia3, which are highly expressed in T cells and which localize to the IS upon TCR activation, as the critical formins mediating this process. Our findings therefore describe previously unsuspected roles for mDia1 and mDia3 in the spatiotemporal control of Zap70-dependent LAT phosphorylation at the IS through regulation of filamentous actin, and underscore their physiological importance in TCR signaling.

Dacomitinib, a second-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) to treat non-small cell lung cancer.

Dacomitinib (PF-00299804, Vizimpro) was developed as a second-generation, oral, irreversible inhibitor of human epidermal growth factor receptor (EGFR)- 1, -2 and -4 tyrosine kinase. On September 27, 2018, the United States Food and Drug Administration (FDA) approved dacomitinib for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletion or exon 21 L858R substitution mutations. On January 8, 2019, the Ministry of Health, Labour and Welfare of Japan approved this second-generation EGFR tyrosine kinase inhibitor (TKI) for the treatment of EGFR mutation-positive inoperable or recurrent NSCLC. The European Commission also approved dacomitinib on April 3, 2019, as monotherapy for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR activating mutations. Approval of dacomitinib was based on a randomized, multicenter, open-label, active-controlled trial (ARCHER 1050; ClinicalTrials.gov Identifier NCT01774721) which demonstrated the safety and efficacy of dacomitinib compared to gefitinib in 452 patients with unresectable and metastatic NSCLC. Dacomitinib represents a powerful new treatment option compared with first-generation EGFR-TKIs. In this paper, we review the clinical and preclinical studies of dacomitinib and discuss the drug's clinical value.

Long-lasting poloidal ULF waves observed by multiple satellites and high-latitude SuperDARN radars.

Poloidal ultra-low frequency (ULF) waves between 5-10 mHz were observed by multiple satellites and three high-latitude Super Dual Auroral Radar Network (SuperDARN) radars during the recovery phase of a moderate geomagnetic storm on Jan 24-27, 2016. The long-lasting ULF waves were observed in the magnetic field and energetic particle flux perturbations during three successive passes by two Geostationary Operational Environmental Satellites (GOES) through the dayside magnetosphere, during which plasmasphere expansion and refilling were observed by two Time History of Events and Macroscale Interactions during Substorms (THEMIS) probes. The radial magnetic field oscillation was in phase (~ 180° out of phase) with the northward (southward) moving proton flux oscillation at 95 keV, consistent with high-energy drift-bounce resonance signatures of protons with second harmonic poloidal standing Alfvén waves. The longitudinal extent of the waves approached 10 hours in local time on the dayside and gradually decreased with time. High-time resolution (~ 6 s) data from three high-latitude SuperDARN radars show that the wave intensification region was localized in latitude with a radial extent of ~ 135-225 km in the subauroral ionosphere. No signature of these waves were observed by ground-based magnetometers colocated with the GOES satellites suggesting that the poloidal waves were high-m mode and thus screened by the ionosphere. During this interval one of the THEMIS probes observed a bump-on-tail ion distribution at 1-3 keV which we suggest is the source of the long-lasting second harmonic poloidal ULF waves.

Search for Boosted Dark Matter Interacting with Electrons in Super-Kamiokande.

A search for boosted dark matter using 161.9 kt yr of Super-Kamiokande IV data is presented. We search for an excess of elastically scattered electrons above the atmospheric neutrino background, with a visible energy between 100 MeV and 1 TeV, pointing back to the Galactic center or the Sun. No such excess is observed. Limits on boosted dark matter event rates in multiple angular cones around the Galactic center and Sun are calculated. Limits are also calculated for a baseline model of boosted dark matter produced from cold dark matter annihilation or decay. This is the first experimental search for boosted dark matter from the Galactic center or the Sun interacting in a terrestrial detector.

Results of a multi-institutional, randomized, non-inferiority, phase III trial of accelerated fractionation versus standard fractionation in radiation therapy for T1-2N0M0 glottic cancer: Japan Clinical Oncology Group Study (JCOG0701).

Background: We assessed the non-inferiority of accelerated fractionation (AF) (2.4 Gy/fraction) compared with standard fractionation (SF) (2 Gy/fraction) regarding progression-free survival (PFS) in patients with T1-2N0M0 glottic cancer (GC). Patients and methods: In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20-80, Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. Patients were randomly assigned to receive either SF of 66-70 Gy (33-35 fractions), or AF of 60-64.8 Gy (25-27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%. Results: Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9% (95% confidence interval [CI] 73.4-85.4) for SF and 81.7% (95% CI 75.4-87.0) for AF (difference 1.8%, 91% CI-5.1% to 8.8%; one-sided P = 0.047 > 0.045). The cumulative incidences of local failure at 3 years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms. Conclusion: Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC. Clinical trials registration: UMIN Clinical Trial Registry, number UMIN000000819.

The comparison of nasal surgery and CPAP on daytime sleepiness in patients with OSAS.

OBJECTIVE: Residual sleepiness after continuous positive airway pressure (CPAP) is a critical problem in some patients with obstructive sleep apnea syndrome (OSAS). However, nasal surgery is likely to reduce daytime sleepiness and feelings of unrefreshed sleep. The aim of this study is to clarify the effects of nasal surgery and CPAP on daytime sleepiness. METHODOLOGY: This is a retrospective and matched-case control study. The participants were consecutive 40 patients with OSAS who underwent nasal surgery (Surgery group) and 40 matched patients who were treated with CPAP (CPAP group). RESULTS: In the Surgery group, although the nasal surgery did not decrease either apnea or hypopnea, it improved oxygenation, the quality of sleep. In the CPAP Group, the CPAP treatment reduced apnea and hypopnea, and improved oxygenation, quality of sleep. The degree of relief from daytime sleepiness was different between the two groups. The improvement of Epworth Sleepiness Scale was more significant in the Surgery Group than those in the CPAP Group (Surgery from 11.0 to 5.1, CPAP from 10.0 to 6.2). DISCUSSION: These findings suggest that the results of the nasal surgery is more satisfactory for some patients with OSAS than CPAP on daytime sleepiness.

Self-adjustment and disintegration threshold of Langmuir solitons in inhomogeneous plasmas.

Dynamics of Langmuir solitons in the presence of a background density gradient is investigated numerically, including cases with steep gradients to the extent the solitons can disintegrate. The disintegration threshold is explained by regarding the electric field part of the soliton as a point mass moving along the self-generated potential well corresponding to the density cavity. On the other hand, it is demonstrated that the Langmuir solitons are robust when the density gradient is below the threshold. During the acceleration phase toward low density regions, Langmuir solitons adjust themselves to balance the electric field pressure and the negative plasma pressure by expelling the imbalanced portion as density cavities at the sound velocity. When the density gradient is below the disintegration threshold, the electric field part of the soliton bounces back and forth within the potential well suggesting the solitons have internal structures.

Fast Heating of Imploded Core with Counterbeam Configuration.

A tailored-pulse-imploded core with a diameter of 70 µm is flashed by counterirradiating 110 fs, 7 TW laser pulses. Photon emission (>40 eV) from the core exceeds the emission from the imploded core by 6 times, even though the heating pulse energies are only one seventh of the implosion energy. The coupling efficiency from the heating laser to the core using counterirradiation is 14% from the enhancement of photon emission. Neutrons are also produced by counterpropagating fast deuterons accelerated by the photon pressure of the heating pulses. A collisional two-dimensional particle-in-cell simulation reveals that the collisionless two counterpropagating fast-electron currents induce mega-Gauss magnetic filaments in the center of the core due to the Weibel instability. The counterpropagating fast-electron currents are absolutely unstable and independent of the core density and resistivity. Fast electrons with energy below a few MeV are trapped by these filaments in the core region, inducing an additional coupling. This might lead to the observed bright photon emissions.

Scaling up nano-milling of poorly water soluble compounds using a rotation/revolution pulverizer.

We previously reported that a rotation/revolution pulverizer (NP-100) could mill a small amount of a drug (0.1 g) into nanoparticles in several minutes. In this investigation, scale up from the milligram to the kilogram scale of the nano-milling process by the rotation/revolution pulverizer was studied. Phenytoin was used as a model drug with low solubility in water. After confirming the improvement of the phenytoin bioavailability by milling to nanoparticles using NP-100, scaling parameters were evaluated using NP-100 and the middle scale model of NP-100 (ARV-3000T). A theoretical equation for the specific collisional energy was adapted for wet milling; this suggested that the relative centrifugal acceleration of revolution (revolution G) and the drug concentration in the suspension were the two most important parameters. The results obtained using NP-100 and ARV-3000T correlated well when these two parameters were identical. These results were applied to the large scale model of NP-100 (ARV-10KT), where 2 kg (1 kg x 2) of phenytoin nanoparticles were obtained in 60 min. The results from PXRD and DSC indicated that the milled phenytoin by ARV-3000T and ARV-10KT maintained its crystallinity. These results suggest nano-milling using a rotation/revolution pulverizer will be widely applicable to the development of nano-medicine.

Search for Nucleon and Dinucleon Decays with an Invisible Particle and a Charged Lepton in the Final State at the Super-Kamiokande Experiment.

Search results for nucleon decays p→e^{+}X, p→µ^{+}X, n→νγ (where X is an invisible, massless particle) as well as dinucleon decays np→e^{+}ν, np→µ^{+}ν, and np→τ^{+}ν in the Super-Kamiokande experiment are presented. Using single-ring data from an exposure of 273.4 kton·yr, a search for these decays yields a result consistent with no signal. Accordingly, lower limits on the partial lifetimes of τ_{p→e^{+}X}>7.9×10^{32} yr, τ_{p→µ^{+}X}>4.1×10^{32} yr, τ_{n→νγ}>5.5×10^{32} yr, τ_{np→e^{+}ν}>2.6×10^{32} yr, τ_{np→µ^{+}ν}>2.2×10^{32} yr, and τ_{np→τ^{+}ν}>2.9×10^{31} yr at a 90% confidence level are obtained. Some of these searches are novel.