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Background Chondrosarcoma of the maxilla is extremely rare, requiring complete surgical resection with clear margins. Various surgical approaches have been used for wide surgical resection of chondrosarcomas in the head and neck region. 3D printed bone models are useful surgical and educational tools.Case A 69-year-old man presented with a grade II chondrosarcoma of the maxilla. This tumor was resected by otolaryngologists and dental surgeons using an anterior segmental maxillary osteotomy and open rhinoplasty approach with the assistance of a 3D-printed bone model.Conclusion Chondrosarcomas can be differentiated from chondromas by their higher mean apparent diffusion coefficient (ADC) on diffusion-weighted magnetic resonance imaging. The anterior segmental maxillary osteotomy and rhinoplasty approach, with ideal osteotomy and a good visual field, resulted in wide surgical safety margins, improving patient prognosis.

Abstract Background Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr

Background & Aims: Colorectal cancer (CRC) is the third most common cancer in the world. Gut microbiota has recently been implicated in the development of CRC. Actinomyces odontolyticus is one of the most abundant bacteria in the gut of patients with very early stages of CRC. A odontolyticus is an anaerobic bacterium existing principally in the oral cavity, similar to Fusobacterium nucleatum, which is known as a colon carcinogenic bacterium. Here we newly determined the biological functions of A odontolyticus on colonic oncogenesis. Methods: We examined the induction of intracellular signaling by A odontolyticus in human colonic epithelial cells (CECs). DNA damage levels in CECs were confirmed using the human induced pluripotent stem cell-derived gut organoid model and mouse colon tissues in vivo. Results: A odontolyticus secretes membrane vesicles (MVs), which induce nuclear factor kappa B signaling and also produce excessive reactive oxygen species (ROS) in colon epithelial cells. We found that A odontolyticus secretes lipoteichoic acid-rich MVs, promoting inflammatory signaling via TLR2. Simultaneously, those MVs are internalized into the colon epithelial cells, co-localize with the mitochondria, and cause mitochondrial dysfunction, resulting in excessive ROS production and DNA damage. Induction of excessive DNA damage in colonic cells by A odontolyticus-derived MVs was confirmed in the gut organoid model and also in mouse colon tissues. Conclusions: A odontolyticus secretes MVs, which cause chronic inflammation and ROS production in colonic epithelial cells, leading to the initiation of CRC.

After the Fukushima nuclear power plant accident in 2011, many types of survey meters were used, including Geiger–Müller (GM) survey meters, which have long been used to measure β-rays. Recently, however, a novel radiation survey meter that uses a plastic-scintillation sensor has been developed. Although manufacturers’ catalog data are available for these survey meters, there have been no user reports on performance. In addition, the performance of commercial plastic-scintillation survey meters has not been evaluated. In this study, we experimentally compared the performance of a plastic-scintillation survey meter with that of a GM survey meter. The results show that the two instruments performed very similarly in most respects. The GM survey meter exhibited count losses when the radiation count rate was high, whereas the plastic-scintillation survey meter remained accurate under such circumstances, with almost no count loss at high radiation rates. For measurements at background rates (i.e., low counting rates), the counting rates of the plastic-scintillation and GM survey meters were similar. Therefore, an advantage of plastic-scintillation survey meters is that they are less affected by count loss than GM survey meters. We conclude that the plastic-scintillation survey meter is a useful β-ray measuring/monitoring instrument.

The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving antigen immunotherapy (AIT) have not been fully clarified. Therefore, we started to perform house dust mite sublingual immunotherapy (HDM-SLIT) for 20 patients with atopic asthma comorbid with allergic rhinitis (AA+AR) who were already receiving ordinary treatments including inhaled corticosteroid (ICS). We examined percentages of circulating T follicular helper (cTfh) and regulatory (cTfr) cells and percentages of circulating regulatory T (cTreg) and B (cBreg) cells by FACS and we examined levels of Der-p/f sIgs by ELISA. Based on the symptom score (asthma control questionnaire: ACQ) and medication score ((global initiative for asthma: GINA) treatment step score) in patients with AA, the patients were divided into responders and non-responders. The percentage of cTfh2 cells significantly decreased and the percentage of cTfh1 cells significantly increased within the first year. Der-p/f sIgEs decreased after a transient elevation at 3 months in both groups. Notably, the percentage of cTfh2 cells and the ratio of cTfh2/cBreg cells and Der-p/f sIgEs greatly decreased in responders from 6 months to 12 months. The percentages of cTfr and cTreg cells showed significant negative correlations with the percentage of cTfh2 cells. The percentage of IL-4+ cTfh cells were significantly decreased and the percentage of IFN-γ+ cTfh cells were increased before treatment to 24 months in 6 patients examined (4 responders and 2 non-responders). We performed multi plelogistic regression analysis based on these results, the ratios of cTfh2/cTfr cells and cTfh2/cBreg cells at the start of therapy were statistically effective biomarkers for predicting the response to HDM-SLIT in patients with AA+AR.

IntroductionRecent studies have suggested associations between RNF213 variants and the formation of periventricular anastomosis among patients with moyamoya disease, leading to early onset of cerebral hemorrhage and rebleeding.Case descriptionWe report herein the case of a boy with Down syndrome and moyamoya syndrome. Exome sequencing identified a heterozygous RNF213 R4810K variant. After ischemic stroke occurred at 9 years old, indirect surgical revascularization was performed for the left cerebral hemisphere and improved ischemic symptoms and cerebral hypoperfusion, while the left choroidal anastomosis remained. At 13 years old, he presented with left thalamic hemorrhage attributed to the anterior choroidal artery, with rebleeding observed four days after the initial hemorrhage under strict blood pressure control. The patient was discharged without neurological deficits 20 days after the hemorrhagic stroke.ConclusionPresence of an RNF213 variant and choroidal anastomosis may represent risk factors for cerebral hemorrhage in patients with Down syndrome and moyamoya syndrome, as well as in patients with moyamoya disease.

Fermi-level pinning (FLP) at the metal/Ge interface makes it difficult to control the Schottky barrier height, which forces an ohmic behavior on p-Ge and a rectifying behavior on n-Ge. This study first demonstrates the rectifying behavior on polycrystalline (poly) p-Ge on a glass substrate, using sputter-deposited ZrN contacts under 350 °C process. The rectifying characteristics depend on the poly-Ge quality derived from the grain size and the defect-induced acceptor density. The highest quality Ge is formed by solid-phase crystallization (SPC) of amorphous Ge deposited at 125 °C and exhibits the lowest reverse leakage current as well as the highest hole (the lowest electron) barrier comparable to a single-crystal Ge substrate. In contrast, the Zr contact exhibits ohmic behavior, suggesting the importance of ZrN in alleviating FLP. The forward and reverse currents are determined by Ge resistance and grain boundaries in Ge, respectively. These technologies will further aid the development of electronic devices on glass or plastic substrates with low heat resistance, including n-channel thin-film transistors.

Abstract Objective Researchers have investigated human altruism toward strangers for decades, using economic games such as the dictator game (DG) in their experiments. However, factors that cause the allocating behavior exhibited by those participants willing to be recipients in the DG have not been identified and the psychological mechanism of avoiding decision-making in economic games has not been widely addressed in previous studies. This study aimed to replicate previous findings regarding the number of people who are willing to be assigned the role of recipient and their allocation behavior and to explore why they share more than people who are willing to be dictators. Results We demonstrate that there are people willing to be assigned the role of the recipient, rather than the role of the dictator during the dictator game. In addition, we find evidence indicating that people who are willing to be recipients behave more altruistically in the dictator game than those who prefer to be dictators. Based on our results, we argue that willingness to be a recipient, in relation to the psychological unwillingness to assume responsibility and reputational concerns, is a strategic consideration.

In the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects surfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy. Less is known about the impacts of gestational African-lineage ZIKV infections. Given high human immunodeficiency virus (HIV) burdens in regions where African-lineage ZIKV circulates, we evaluated whether pregnant rhesus macaques infected with simian immunodeficiency virus (SIV) have a higher risk of African-lineage ZIKV-associated birth defects. Remarkably, in both SIV+ and SIV- animals, ZIKV infection early in the first trimester caused a high incidence (78%) of spontaneous pregnancy loss within 20 days. These findings suggest a significant risk for early pregnancy loss associated with African-lineage ZIKV infection and provide the first consistent ZIKV-associated phenotype in macaques for testing medical countermeasures.

Background. Previous reports have revealed various endovascular intervention techniques for prosthetic femoropopliteal bypass occlusion (PFPBO); however, treatment for PFPBO remains challenging for most interventionalists and vascular surgeons because the procedure is complicated. Most of the reported techniques involve device implantation. In the present study, we performed a combination of surgical graft thrombectomy and drug-coated balloon angioplasty for PFPBO without implanting any additional devices. Furthermore, we determined the favorable long-term results of this treatment using follow-up angiography. Case Presentation. A 77-year-old man with a history of chronic kidney disease and coronary artery disease presented to our clinic with rest pain on his left leg. Seven years prior to the current consult, he underwent femoropopliteal bypass (FPB) surgery using a prosthetic graft due to in-stent occlusion of the left superficial femoral artery (SFA). Four years after surgery, a duplex ultrasound scan revealed stenosis of the proximal anastomosis site; hence, medical therapy was continued. On the current consult, diagnostic angiography revealed occlusion of the FPB and infrapopliteal vessels. In the first attempt at recanalization, the guidewire was unable to pass through the occluded SFA. Therefore, another technique was performed to revascularize the FPBO and infrapopliteal vessels. We obtained an angiography of the left leg after inserting the guiding sheath via the right common femoral artery (CFA). First, surgical thrombectomy using a Fogarty catheter via the exposed left CFA was performed. Following endovascular therapy via the right CFA, we performed drug-coated balloon angioplasty for anastomotic stenosis and recanalized occlusive infrapopliteal vessels. Restenosis was not observed on follow-up angiograms. On further follow-up angiography, there was notable regression of the residual stenosis at the proximal anastomosis of the prosthetic graft. Conclusion. This novel revascularization strategy may be a viable treatment option for PFPBO.

BackgroundFractional flow reserve (FFR) is the current gold standard for identifying myocardial ischemia in individuals with coronary artery stenosis. However, FFR is not penetrated as much worldwide due to time consumption, costs associated with adenosine, FFR-related discomfort, and complications. Resting physiological indexes may be widely accepted alternatives to FFR, while the discrepancies with FFR were found in up to 20% of lesions. The saline-induced Pd/Pa ratio (SPR) is a new simplified option for evaluating coronary stenosis. However, the clinical implication of SPR remains unclear.ObjectivesIn the present study, we aimed to compare the accuracies of SPR and resting full-cycle ratio (RFR) and to investigate the incremental value of SPR in clinical practice.MethodsIn this multicenter prospective study, 112 coronary lesions (105 patients) were evaluated by SPR, RFR, and FFR.ResultsThe overall median age was 71 years, and 84.8% were men. SPR was correlated more strongly with FFR than with RFR (r = 0.874 vs. 0.713, respectively; p < 0.001). Using FFR < 0.80 as the reference standard variable, the area under the receiver-operating characteristic (ROC) curve for SPR was superior to that of RFR (0.932 vs. 0.840, respectively; p = 0.009).ConclusionSaline-induced Pd/Pa ratio predicted FFR more accurately than RFR. SPR could be an alternative method for evaluating coronary artery stenosis and further investigation including elucidation of the mechanism of SPR is needed (225 words).

Countermeasures against Zika virus (ZIKV), including vaccines, are frequently tested in nonhuman primates (NHP). Macaque models are important for understanding how ZIKV infections impact human pregnancy due to similarities in placental development. The lack of consistent adverse pregnancy outcomes in ZIKV-affected pregnancies poses a challenge in macaque studies where group sizes are often small (4-8 animals). Studies in small animal models suggest that African-lineage Zika viruses can cause more frequent and severe fetal outcomes. No adverse outcomes were observed in macaques exposed to 1x104 PFU (low dose) of African-lineage ZIKV at gestational day (GD) 45. Here, we exposed eight pregnant rhesus macaques to 1x108 PFU (high dose) of African-lineage ZIKV at GD 45 to test the hypothesis that adverse pregnancy outcomes are dose-dependent. Three of eight pregnancies ended prematurely with fetal death. ZIKV was detected in both fetal and placental tissues from all cases of early fetal loss. Further refinements of this exposure system (e.g., varying the dose and timing of infection) could lead to an even more consistent, unambiguous fetal loss phenotype for assessing ZIKV countermeasures in pregnancy. These data demonstrate that high-dose exposure to African-lineage ZIKV causes pregnancy loss in macaques and also suggest that ZIKV-induced first trimester pregnancy loss could be strain-specific.

Abstract The incidence of central nervous system (CNS) metastases in patients with anaplastic lymphoma kinase (ALK) fusion gene‐positive (ALK+) non‐small cell lung cancer (NSCLC) is high, ranging from approximately 20%–70%. Although ALK inhibitors (ALKis) are generally effective for CNS metastases in patients with ALK+ NSCLC, relapse with CNS metastases is frequently observed. A 37‐year‐old woman with a high level of carcinoembryonic antigen was diagnosed with right lung adenocarcinoma (pathological stage IIIA) and underwent right lower lobectomy. Despite the administration of postoperative chemotherapy, her carcinoembryonic antigen (CEA) level remained elevated. Although crizotinib was administered due to the positivity for ALK fusion, brain metastases appeared at 19.0 months after the start of treatment. Treatment with alectinib following crizotinib resulted in the complete disappearance of brain metastases. However, brain metastases relapsed, and meningeal dissemination appeared at 38.3 months after the start of treatment with alectinib. Although ceritinib, brigatinib, and alectinib rechallenge were attempted, the CNS lesions worsened. Lorlatinib was then administered, resulting in the normalization of the CEA level (4.5 ng/ml) 4.1 months after the start of lorlatinib. The brain metastases and meningeal dissemination almost disappeared. The overall time from the start of crizotinib to lorlatinib is 89.5 months at present, and the patient continues to be treated with lorlatinib without relapse. Lorlatinib was effective in this case with brain metastases and meningeal dissemination after resistance to first‐ and second‐generation ALKis. Appropriate sequential treatment with first‐, second‐ and third‐generation ALKis can lead to a long‐term survival in ALK+ patients with brain metastases and meningeal dissemination.

Abstract While the significance of acquired genetic abnormalities in the initiation of hepatocellular carcinoma (HCC) has been established, the role of epigenetic modification remains unknown. Here we identified the pivotal role of histone methyltransferase G9a in the DNA damage-triggered initiation of HCC. Using liver-specific G9a-deficient (G9a ΔHep) mice, we revealed that loss of G9a significantly attenuated liver tumor initiation caused by diethylnitrosamine (DEN). In addition, pharmacological inhibition of G9a attenuated the DEN-induced initiation of HCC. After treatment with DEN, while the induction of γH2AX and p53 were comparable in the G9a ΔHep and wild-type livers, more apoptotic hepatocytes were detected in the G9a ΔHep liver. Transcriptome analysis identified Bcl-G, a pro-apoptotic Bcl-2 family member, to be markedly upregulated in the G9a ΔHep liver. In human cultured hepatoma cells, a G9a inhibitor, UNC0638, upregulated BCL-G expression and enhanced the apoptotic response after treatment with hydrogen peroxide or irradiation, suggesting an essential role of the G9a-Bcl-G axis in DNA damage response in hepatocytes. The proposed mechanism was that DNA damage stimuli recruited G9a to the p53-responsive element of the Bcl-G gene, resulting in the impaired enrichment of p53 to the region and the attenuation of Bcl-G expression. G9a deletion allowed the recruitment of p53 and upregulated Bcl-G expression. These results demonstrate that G9a allows DNA-damaged hepatocytes to escape p53-induced apoptosis by silencing Bcl-G, which may contribute to the tumor initiation. Therefore, G9a inhibition can be a novel preventive strategy for HCC.

There are currently no approved drugs to treat Zika virus (ZIKV) infection during pregnancy. Hyperimmune globulin products such as VARIZIG and WinRho are FDA-approved to treat conditions during pregnancy such as Varicella Zoster virus infection and Rh-incompatibility. We administered ZIKV-specific human immune globulin as a treatment in pregnant rhesus macaques one day after subcutaneous ZIKV infection. All animals controlled ZIKV viremia following the treatment and generated robust levels of anti-Zika virus antibodies in their blood. No adverse fetal or infant outcomes were identified in the treated animals, yet the placebo control treated animals also did not have signs related to congenital Zika syndrome (CZS). Human immune globulin may be a viable prophylaxis and treatment option for ZIKV infection during pregnancy, however, more studies are required to fully assess the impact of this treatment to prevent CZS.

Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that macaques with a prior DENV-2 exposure had a higher burden of ZIKV vRNA in maternal-fetal interface tissues as compared to DENV-naive macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with only a few effective therapeutic options. A characteristic feature of PDAC is its unique tumor microenvironment (TME), termed desmoplasia, which shows extensive fibrosis and extracellular matrix deposition, generating highly hypoxic and nutrient-deprived conditions within the tumor. To thrive in this harsh TME, PDAC undergoes extensive metabolic rewiring that includes the altered use of glucose and glutamine, constitutive activation of autophagy-lysosomal pathways, and nutrient acquisition from host cells in the TME. Notably, these properties support PDAC metabolism and mediate therapeutic resistance, including immune suppression. A deeper understanding of the unique metabolic properties of PDAC and its TME may aid in the development of novel therapeutic strategies against this deadly disease.

The APOBEC3 deaminases are potent inhibitors of virus replication and barriers to cross-species transmission. For simian immunodeficiency virus (SIV) to transmit to a new primate host, as happened multiple times to seed the ongoing HIV-1 epidemic, the viral infectivity factor (Vif) must be capable of neutralizing the APOBEC3 enzymes of the new host. Although much is known about current interactions of HIV-1 Vif and human APOBEC3s, the evolutionary changes in SIV Vif required for transmission from chimpanzees to gorillas and ultimately to humans are poorly understood. Here, we demonstrate that gorilla APOBEC3G is a factor with the potential to hamper SIV transmission from chimpanzees to gorillas. Gain-of-function experiments using SIVcpzPtt Vif revealed that this barrier could be overcome by a single Vif acidic amino acid substitution (M16E). Moreover, degradation of gorilla APOBEC3F is induced by Vif through a mechanism that is distinct from that of human APOBEC3F. Thus, our findings identify virus adaptations in gorillas that preceded and may have facilitated transmission to humans.

Interface traps (ITs) and border traps (BTs) in Al2O3/GeOx/p-Ge gate stacks were characterized using deep-level transient spectroscopy. Through evaluating the gate stacks with different GeOx thicknesses, the respective BTs in Al2O3, the Al2O3/GeOx interface region, and GeOx were detected. The density of ITs (Dit) near the midgap is lower in the metal-oxide-semiconductor (MOS) capacitors with thicker GeOx, while Dit near the valence band is lower in the MOS capacitor with thinner GeOx. The density of BTs (Nbt) in Al2O3 (6–9 × 1017 cm−3) is lower than those in GeOx (∼2 × 1018 cm−3), and the highest Nbt (∼1 × 1019 cm−3) was found in the Al2O3/GeOx interface region. Ge p-channel metal-oxide-semiconductor field-effect-transistors (MOSFETs) with Al2O3/GeOx/p-Ge gate stacks were fabricated and analyzed. We confirmed that the ITs and the BTs near the valence band edge of Ge affect the effective mobility of Ge p-MOSFETs in the high-field region.

Abstract Background The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) gene family appears only in mammalian genomes. Some A3 proteins can be incorporated into progeny virions and inhibit lentiviral replication. In turn, the lentiviral viral infectivity factor (Vif) counteracts the A3-mediated antiviral effect by degrading A3 proteins. Recent investigations have suggested that lentiviral vif genes evolved to combat mammalian APOBEC3 proteins, and have further proposed that the Vif-A3 interaction may help determine the co-evolutionary history of cross-species lentiviral transmission in mammals. Results Here we address the co-evolutionary relationship between two New World felids, the puma (Puma concolor) and the bobcat (Lynx rufus), and their lentiviruses, which are designated puma lentiviruses (PLVs). We demonstrate that PLV-A Vif counteracts the antiviral action of APOBEC3Z3 (A3Z3) of both puma and bobcat, whereas PLV-B Vif counteracts only puma A3Z3. The species specificity of PLV-B Vif is irrespective of the phylogenic relationships of feline species in the genera Puma, Lynx and Acinonyx. We reveal that the amino acid at position 178 in the puma and bobcat A3Z3 is exposed on the protein surface and determines the sensitivity to PLV-B Vif-mediated degradation. Moreover, although both the puma and bobcat A3Z3 genes are polymorphic, their sensitivity/resistance to PLV Vif-mediated degradation is conserved. Conclusions To the best of our knowledge, this is the first study suggesting that the host A3 protein potently controls inter-genus lentiviral transmission. Our findings provide the first evidence suggesting that the co-evolutionary arms race between lentiviruses and mammals has occurred in the New World.

Background: Periostin and squamous cell carcinoma antigen (SCCA) are involved in the pathogenesis of asthma. Acute bronchitis due to respiratory syncytial virus (RSV) infection during infancy exhibits an asthma-like pathogenesis, suggesting that it may be associated with the subsequent development of asthma. However, the mechanism by which RSV infection leads to development of asthma has not yet been fully elucidated. Methods: Infants younger than 36 months were enrolled and classified into three groups. Group I included patients hospitalized with RSV-induced bronchitis. These patients were further stratified into two sub-groups according to whether the criteria for the modified Asthma Predictive Index (mAPI) had been met: Group I consisted of mAPI (+) and mAPI (−) patients; Group II included patients with food allergy as a positive control group; and Group III included children with no allergy as a negative control group. Serum periostin and SCCA levels were measured in the groups. This study was registered as a clinical trial (UMIN000012339). Results: We enrolled 14 subjects in Group I mAPI (+), 22 in Group I mAPI (−), 18 in Group II, and 18 in Group III. In Group I, the serum periostin and SCCA levels were significantly higher during the acute phase compared with the recovery phase. However, no significant differences were found between Group I mAPI (+) and mAPI (−). Conclusions: The serum periostin and SCCA levels increased during acute RSV bronchitis. Both periostin and SCCA may play a role in the pathogenesis of acute bronchitis due to RSV. Keywords: Infants, Periostin, Respiratory syncytial virus, Squamous cell carcinoma antigen, T-helper 2 cell cytokines

Zika virus (ZIKV) and dengue virus (DENV) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world. The rapid emergence of ZIKV in the Americas in 2015 and 2016, and its recent associations with Guillain-Barré syndrome, birth defects, and fetal loss have led to the hypothesis that DENV infection induces cross-reactive antibodies that influence the severity of secondary ZIKV infections. It has also been proposed that pre-existing ZIKV immunity could affect DENV pathogenesis. We examined outcomes of secondary ZIKV infections in three rhesus and fifteen cynomolgus macaques, as well as secondary DENV-2 infections in three additional rhesus macaques up to a year post-primary ZIKV infection. Although cross-binding antibodies were detected prior to secondary infection for all animals and cross-neutralizing antibodies were detected for some animals, previous DENV or ZIKV infection had no apparent effect on the clinical course of heterotypic secondary infections in these animals. All animals had asymptomatic infections and, when compared to controls, did not have significantly perturbed hematological parameters. Rhesus macaques infected with DENV-2 approximately one year after primary ZIKV infection had higher vRNA loads in plasma when compared with serum vRNA loads from ZIKV-naive animals infected with DENV-2, but a differential effect of sample type could not be ruled out. In cynomolgus macaques, the serotype of primary DENV infection did not affect the outcome of secondary ZIKV infection.

Silicosis is an occupational lung disorder caused by inhalation of silica dust. It not only causes respiratory disorders but also affects other organs. We report an extremely rare case of silicosis complicated by pericarditis in an 83-year-old male. He had been working as a coal miner and was diagnosed with silicosis at the age of 63. Because he had experienced repeated pericardial effusions, he was referred for a surgical pericardial biopsy to elucidate the cause of his repeated pericardial effusion and to perform pericardial fenestration. Thoracoscopic surgery was performed. The pericardium was resected, and a drain was placed in the left thoracic cavity. Histopathological examination revealed the pericardial degeneration due to silicosis, suggesting that pericarditis and pericardial effusion are related to silicosis. The operation was successful, and he experienced no recurrence of pericardial effusion at the 7-month follow-up.

Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome and its infection leads to the onset of several disorders such as the depletion of peripheral CD4+ T cells and immune activation. HIV-1 is recognized by innate immune sensors that then trigger the production of type I interferons (IFN-Is). IFN-Is are well-known cytokines eliciting broad anti-viral effects by inducing the expression of anti-viral genes called interferon-stimulated genes (ISGs). Extensive in vitro studies using cell culture systems have elucidated that certain ISGs such as APOBEC3G, tetherin, SAM domain and HD domain-containing protein 1, MX dynamin-like GTPase 2, guanylate-binding protein 5, and schlafen 11 exert robust anti-HIV-1 activity, suggesting that IFN-I responses triggered by HIV-1 infection are detrimental for viral replication and spread. However, recent studies using animal models have demonstrated that at both the acute and chronic phase of infection, the role of IFN-Is produced by HIV or SIV infection in viral replication, spread, and pathogenesis, may not be that straightforward. In this review, we describe the pluses and minuses of HIV-1 infection stimulated IFN-I responses on viral replication and pathogenesis, and further discuss the possibility for therapeutic approaches.

This study presents a simple, accurate, and selective bioanalytical method of bevacizumab detection from plasma samples based on aptamer affinity purification⁻high-temperature reversed-phased liquid chromatography (HT-RPLC) with fluorescence detection. Bevacizumab in plasma samples was purified using magnetic beads immobilized with an anti-idiotype DNA aptamer for bevacizumab. The purified bevacizumab was separated with HT-RPLC and detected with its native fluorescence. Using aptamer affinity beads, bevacizumab was selectively purified and detected as a single peak in the chromatogram. HT-RPLC achieved good separation for bevacizumab with a sharp peak within 10 min. The calibration curves of the two monoclonal antibodies ranged from 1 to 50 μg/mL and showed good correlation coefficients (r2 > 0.999). The limit of detection (LOD) and lower limit of quantification (LLOQ) values for bevacizumab were 0.15 and 0.51 μg/mL, respectively. The proposed method was successfully applied to the bioanalysis of the plasma samples obtained from the patients with lung cancer and may be extended to plan optimal therapeutic programs and for the evaluation of biological equivalencies in the development of biosimilars.

Stress granules (SGs) are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV) induced SGs depending on activation of protein kinase R (PKR). MuV infection strongly induced interferon (IFN)-λ1, 2 and 3, and IFN-β through activation of IFN regulatory factor 3 (IRF3) via retinoic acid inducible gene-I (RIG-I) and the mitochondrial antiviral signaling (MAVS) pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen-1, and significantly increased the levels of MuV-induced IFN-λ1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-λ1) mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection.

We performed first-principles-based calculations of density of states, electrical conductivity, Seebeck coefficient, and thermal conductivity of a p-type half-Heusler compounds (ZrCoSb) to identify the alloy composition that gives rise to a high thermoelectric figure-of-merit. The strategy here is to substitute constituent atoms of ZrCoSb with lighter or heavier homologous element to reduce thermal conductivity without appreciably altering electrical properties. The density-of-states calculations reveal that substitution of Sb does not singnificantly alter the electronic states near Fermi level. The small influence on electrical properties was also confirmed by performing calculations for ZrCoBi, where the power factor is slightly larger than that of ZrCoSb. The effect of alloying on thermal conductivity reduction was quantified by equilibrium molecular dynamics simulations of ZrCoSb1-xBix with force fields obtained from first principles. With increasing alloy fraction x, thermal conductivity rapidly reduces to less than 15% of that of ZrCoSb and nearly saturates above x～20%, suggesting ZrCoSb0.8Bi0.2 to be a reasonable alloy composition for high thermoelectric performance.

The development of novel fertilization treatments, including in vitro fertilization and intracytoplasmic injection, has made pregnancy possible regardless of the level of activity of the spermatozoa; however, the etiology of male-factor infertility is poorly understood. Multiple studies, primarily through the use of transgenic animals, have contributed to a list of candidate genes that may affect male infertility in humans. We examined single nucleotide polymorphisms (SNPs) as a cause of male infertility in an analysis of spermatogenesis-specific genes.We carried out the prevalence of SNPs in the coding region of phosphoglycerate mutase 4 (PGAM4) on the X chromosome by the direct sequencing of PCR-amplified DNA from male patients. Using RT-PCR and western blot analyses, we identified that PGAM4 is a functional retrogene that is expressed predominantly in the testes and is associated with male infertility. PGAM4 is expressed in post-meiotic stages, including spermatids and spermatozoa in the testes, and the principal piece of the flagellum and acrosome in ejaculated spermatozoa. A case-control study revealed that 4.5% of infertile patients carry the G75C polymorphism, which causes an amino acid substitution in the encoded protein. Furthermore, an assay for enzymatic activity demonstrated that this polymorphism decreases the enzyme's activity both in vitro and in vivo.These results suggest that PGAM4, an X-linked retrogene, is a fundamental gene in human male reproduction and may escape meiotic sex chromosome inactivation. These findings provide fresh insight into elucidating the mechanisms of male infertility.