Two autopsied gastric cancer cases of rare drug-induced pneumonia associated with nivolumab plus S-1 and oxaliplatin: a case report.

Background: Drug-induced pneumonia, especially immune-related adverse events, can sometimes be fatal, and it is crucial to seize the signs for early treatment. A clinical trial (ATTRACTION-4) reported no cases of grade 4 or 5 pneumonia or interstitial lung disease associated with nivolumab plus S-1 and oxaliplatin. However, we encountered two cases of fatal pneumonia induced by this regimen. Case Description: The two patients were in their 70s, male and diagnosed gastric cancer with peritoneal dissemination. The patient of case 1 underwent surgery and adjuvant chemotherapy nine years before. The patient of case 2 was diagnosed unresectable 6 months before and chemo naïve. Both patients received nivolumab plus S-1 and oxaliplatin for the dissemination. The onset of both cases occurred after the fifth dose of the regimen, and the responses to corticosteroids were transient and limited. Computed tomography showed bilateral consolidation and ground-glass opacities, seemingly similar to an organizing pneumonia pattern. Acute and organizing stages of diffuse alveolar damage were detected histopathologically. Despite showing notable antitumor effects, both patients had indications of interstitial pneumonitis before admission, such as elevation of C-reactive protein (CRP) and Krebs von den Lungen-6 (KL-6) levels and slight lung opacity or respiratory symptoms approximately 10 days before admission. Conclusions: Patients undergoing nivolumab plus S-1 and oxaliplatin should be closely followed up with imaging, evaluation of symptom including oxygen saturation, and serological marker analysis such as lactate dehydrogenase, CRP, and KL-6. Early detection of pneumonia leads to adequate cessation of chemotherapy and early treatment, and this can prevent severe adverse events.

Estimation of Sound Transmission Loss in Nanofiber Nonwoven Fabrics: Comparison of Conventional Models and the Simplified Limp Frame Model.

Although the sound absorption coefficients of conventional and nanofiber nonwoven fabrics (NF-NWFs) have been the subject of many previous studies, few studies have considered the estimation of transmission loss. Reported herein is an experimental and theoretical study into estimating the transmission loss of NF-NWFs using four estimation models, i.e., the Rayleigh, Miki, and Komatsu models, and the simplified limp frame model (SLFM), with the model results compared against the experimental data. The transmission loss of the NF-NWF was determined from the propagation constant, and characteristic impedance was calculated using the estimation model and the transfer matrix method. The validity of each estimation method was examined by comparing its estimated values with the experimental values measured using a four-microphone impedance measurement tube. The proposed SLFM is more suitable for estimating the transmission loss of NF-NWFs than the conventional Rayleigh, Miki, and Komatsu models.

Theoretical and Experimental Analyses on the Sound Absorption Coefficient of Rice and Buckwheat Husks Based on Micro-CT Scan Data.

In this study, the sound absorption coefficients of rice and buckwheat husks were estimated. Computed tomography (CT) images were processed to determine the circumference and surface area of voids in the granular material, and the normal incident sound absorption coefficients were derived. In addition, the tortuosity, which expresses the complexity of the sound wave propagation through the structure, was measured for each material. The theoretical sound absorption coefficients were then compared to the measured sound absorption coefficients with and without consideration of the tortuosity. A correction factor was used to bring the surface area of the granular material closer to the actual surface area and observed that the tortuosity obtained theoretical values that matched the trend of the measured values. These results indicate that using CT images to estimate the sound absorption coefficient is a viable approach.

Comparison of the risk of ovarian malignancy algorithm and Copenhagen Index for the preoperative assessment of Japanese women with ovarian tumors.

OBJECTIVE: To compare the risk of ovarian malignancy algorithm (ROMA) and Copenhagen Index (CPH-I) in their ability to distinguish epithelial ovarian cancer (EOC) and malignant ovarian tumors (MLOT) from benign ovarian tumors (BeOT) in Japanese women. METHODS: Patients with pathologically diagnosed ovarian tumors were included in this study. The study validated the diagnostic performance of ROMA and CPH-I. RESULTS: Among the 463 Japanese women included in this study, 312 had BeOT, 99 had EOC, and 52 had other MLOT. The receiver-operator characteristic (ROC) area under the curve (AUCs) of ROMA (0.89) and CPH-I (0.89) for distinguishing EOC from BeOT were significantly higher than that of CA125 (0.82) (CA 125 vs. ROMA; p = 0.002, vs. CPH-I; p < 0.001). The ROC-AUCs of ROMA (0.82) and CPH-I (0.81) for distinguishing MLOT from BeOT were significantly higher than that of CA125 (0.75) (CA 125 vs. ROMA: p = 0.003, vs. CPH-I: p < 0.001). The sensitivity (SN)/specificity (SP) of ROMA and CPH-I for distinguishing EOC from BeOT at standard cut-off points were 69%/90%, and 69%/90%, respectively, those for distinguishing MLOT from BeOT were 54%/90%, and 55%/90%, respectively. CONCLUSION: ROMA and CPH-I performed comparably well and better than CA125 in distinguishing EOC from BeOT in Japanese women. ROMA and CHP-I should be used with caution in practical situations, where all histological possibilities for must be considered, because the SNs of ROMA and CPH-I were only 54% and 55%.

Exploring Visual-Auditory Redirected Walking using Auditory Cues in Reality.

We examine the effect of auditory cues occurring in reality on redirection. Specifically, we set two hypotheses: the auditory cues emanating from fixed positions in reality (Fixed sound, FS) increase the noticeability of redirection, while the auditory cues whose positions are manipulated consistently with the visual manipulation (Redirected sound, RDS) decrease the noticeability of redirection. To verify these hypotheses, we implemented an experimental environment that virtually reproduced FS and RDS conditions using binaural recording, and then we conducted a user study ( N=18) to investigate the detection thresholds (DTs) for rotational manipulation and the sound localization accuracy of the auditory cues under FS and RDS, as well as the baseline condition without auditory cues (No sound, NS). The results show, against the hypotheses, FS gave a wider range of DTs than NS, while RDS gave a similar range of DTs to NS. Combining these results with those of sound localization accuracy reveals that, rather than the auditory cues affecting the participants' spatial perception in VR, the visual manipulation made their sound localization less accurate, which would be a reason for the increased range of DTs under FS. Furthermore, we conducted a follow-up user study ( N=11) to measure the sound localization accuracy of FS where the auditory cues were actually placed in a real setting, and we found that the accuracy tended to be similar to that of virtually reproduced FS, suggesting the validity of the auditory cues used in this study. Given these findings, we also discuss potential applications.

Diversity of aphantasia revealed by multiple assessments of visual imagery, multisensory imagery, and cognitive style.

Aphantasia-a condition wherein individuals have a reduced or absent construction of voluntary visual imagery-is diagnosed using either the Vividness of Visual Imagery Questionnaire (VVIQ) or self-identification. However, a significant discrepancy exists between the proportions of aphantasia in the populations assessed using these two criteria. It is unclear why the reported proportions differ excessively and what percentage of people cannot form visual imagery. We investigated the replicability of the proportion of people with aphantasia using both criteria in the same population of participants. Therefore, we explored the potential causes of the discrepancy and characteristics of putative aphantasia in terms of multisensory imagery, cognitive style, and face recognition ability. First, we conducted an online sampling study (Study 1: N = 2,871) using the VVIQ, self-identification of a reduction in visual imagery, Questionnaire upon Mental Imagery (QMI), and Verbalizer-Visualizer Questionnaire (VVQ). We found that 3.7 and 12.1% fulfilled the VVIQ and self-identification criteria, respectively, roughly replicating the proportions reported in previous studies. The self-identification criterion-but not the VVIQ criterion-contains items related to face recognition; hence, we suspected that face recognition ability was factor contributing to this discrepancy and conducted another online sampling study (Study 2: N = 774). We found a significant correlation between VVIQ and face recognition ability in the control group with self-identification, but not in the group defined by low VVIQ (VVIQ ≤32). As the participants in the control group with self-identification tended to exhibit moderately high VVIQ scores but low face recognition ability, we reason that the discrepancy can be partially explained by the contamination of individual differences in face recognition ability. Additional analyses of Study 1 revealed that the aphantasia group included participants who lacked all types of sensory imagery or only visual imagery in multisensory imagery and exhibited a non-specific cognitive style. This study indicates that the VVIQ alone may be insufficient to diagnose individuals who report an inability to form visual imagery. Furthermore, we highlight the importance of multiple assessments-along with the VVIQ-to better understand the diversity of imagery in aphantasia.

Mathematical Model for Estimating the Sound Absorption Coefficient in Grid Network Structures.

Although grid network structures are often not necessarily intended to absorb sound, the gaps between the rods that make up the grid network are expected to have a sound absorption effect. In this study, the one-dimensional transfer matrix method was used to develop a simple mathematical model for accurately estimating the sound absorption coefficient of a grid network structure. The gaps in the grid network structure were approximated as the clearance between two parallel planes, and analysis units were derived to consider the exact geometry of the layers. The characteristic impedance and propagation constant were determined for the approximated gaps and treated as a one-dimensional transfer matrix. The transfer matrix obtained for each layer was used to calculate the sound absorption coefficient. The samples were fabricated from light-curing resin by using a Form2 3D printer from Formlabs. The measurement results showed that a sound absorption coefficient of 0.81 was obtained at the peak when seven layers were stacked. A sensitivity analysis was carried out to investigate the influence of the rod diameter and pitch. The simulated values tended to be close to the experimental values. The above results indicate that the mathematical model used to calculate the sound absorption coefficient is sufficiently accurate to predict the sound absorption coefficient for practical application.

Antisense Gapmers with LNA-Wings and (S)-5'-C-Aminopropyl-2'-arabinofluoro-nucleosides Could Efficiently Suppress the Expression of KNTC2.

Previously reported (S)-5'-C-aminopropyl-2'-arabinofluoro-thymidine (5ara-T) and newly synthesized (S)-5'-C-aminopropyl-2'-arabinofluoro-5-methyl-cytidine (5ara-MeC) analogs were incorporated into a series of antisense gapmers containing multiple phosphorothioate (PS) linkages and locked nucleic acids (LNAs) in their wing regions. The functional properties of the gapmers were further evaluated in vitro. Compared with the positive control, for the LNA-wing full PS gapmer without 5ara modification, it was revealed that each gapmer could have a high affinity and be thermally stable under biological conditions. Although the cleavage pattern was obviously changed; gapmers with 5ara modification could still efficiently activate E. coli RNase H1. In addition, incorporating one 5ara modification into the two phosphodiester linkages could reverse the destabilization in enzymatic hydrolysis caused by fewer PS linkages. In vitro cellular experiments were also performed, and the Lipofectamine® 2000 (LFA)+ group showed relatively higher antisense activity than the LFA-free group. KN5ara-10, which contains fewer PS linkages, showed similar or slightly better antisense activity than the corresponding full PS-modified KN5ara-3. Hence, KN5ara-10 may be the most promising candidate for KNTC2-targeted cancer therapy.

Mathematical Models and Experiments on the Acoustic Properties of Granular Packing Structures (Measurement of Tortuosity in Hexagonal Close-Packed and Face-Centered Cubic Lattices).

In this study, the sound absorption characteristics of hexagonal close-packed and face-centered cubic lattices were estimated by theoretical analysis. Propagation constants and characteristic impedances were obtained by dividing each structure into elements perpendicular to the incident direction of sound waves and by approximating each element to a clearance between two parallel planes. Consequently, the propagation constant and the characteristic impedance were treated as a one-dimensional transfer matrix in the propagation of sound waves, and the normal incident sound absorption coefficient was calculated by the transfer matrix method. The theoretical value of the sound absorption coefficient was derived by using the effective density applied to the measured tortuosity. As a result, the theoretical value was becoming closer to the measured value. Therefore, the measured tortuosity is reasonable.

Simplified Limp Frame Model for Application to Nanofiber Nonwovens (Selection of Dominant Biot Parameters).

This study aimed to discover an easy and precise prediction model for the acoustic properties of nanofiber nonwoven fabrics. For this purpose, a prediction model focusing on the two dominant parameters in the Limp frame model-bulk density and flow resistivity-was suggested. The propagation constant and characteristic impedance was generated from the effective density and effective volume modulus generated by the predictive model and treated as a one-dimensional transfer matrix. The sound absorption coefficient was then estimated using the transfer matrix approach. The trend of the normal Incident sound absorption coefficient measured and the sound absorption coefficient obtained from the predictive model were consistent. Thus, it is suggested that the predictive model for the proposed nanofiber nonwoven composite sheet is valid.

Addition of Two Substantial Side-Branch Silencers to the Interference Silencer by Incorporating a Zero-Mass Metamaterial.

Zero-mass metamaterials comprise an orifice and a thin film. The resonance between the film and the air mass of the orifice hole is caused by sound waves, which significantly decreases the transmission loss at a specific frequency. The study novelly incorporates acoustic metamaterials in the delay tube of an interference silencer. In this case, it is determined that an interference silencer and a "side-branch silencer with two different branch pipe lengths" can be realized in a single silencer. At certain frequencies, the acoustic mass of the acoustic metamaterial approaches zero, which results in an interference silencer with the full length of the delay tube applied. At other frequencies, the acoustic metamaterial acts as a rigid wall with high transmission loss, thereby reflecting sound waves at the zero-mass metamaterial location. In this case, it is a side-branch silencer with two different tube lengths, corresponding to the tube lengths from the entrance and exit of the delay tube to the zero-mass metamaterial, respectively. The incorporation of zero-mass metamaterial into an interference-type silencer can introduce the silencing effect of a side-branch silencer with two different branch tube lengths without increasing the volume of the interference-type silencer. Theoretical values were obtained using the transfer matrix. Consequently, the theoretical and experimental values were close, enabling us to predict the transmission loss of the proposed silencer.

Effect of Sheet Vibration on the Theoretical Analysis and Experimentation of Nonwoven Fabric Sheet with Back Air Space.

The purpose of this study was to improve the accuracy of the theoretical analysis of sound absorption mechanisms when a back air space is used in nonwoven fabrics. In the case of a nonwoven sheet with a back air space, it can be shown that there is a difference between the experimental results and theoretical analysis results obtained using the Miki model when the area of the nonwoven sheet is large. Therefore, in this study, the accuracy of the theoretical values was improved using the plate vibration model in conjunction with the Miki model. The experimental results showed that when the vibration of the nonwoven sheet was suppressed, the sound absorption coefficient was higher than that of the vibration-prone nonwoven sheet alone. The sound absorption coefficient at the peak frequency was increased by >0.2, especially for 3501BD. Using the support frame, the sound absorption coefficient at the peak frequencies of 3A01A and 3701B was increased to 0.99. In the theoretical analysis of a large-area, vibration-prone nonwoven fabric, in which the vibration of the nonwoven fabric was taken into account, the theoretical values were in agreement with the experimental values, and the accuracy of the theoretical values was improved. Comparing the theoretical values for nonwoven fabrics without high ventilation resistance, the sound absorption coefficient was greater when vibration was not considered. Therefore, it was suggested that the vibration of the nonwoven fabric hinders sound absorption.

Temporal and Directional Cue Effects on the Cocktail Party Problem for Patients With Listening Difficulties Without Clinical Hearing Loss.

OBJECTIVES: To evaluate the listening difficulty in a cocktail party environment in the sound field in order to better demonstrate patients' difficulties listening in noise, and to examine temporal and directional cue effects on the speech intelligibility in patients with listening difficulties in noise in comparison with control subjects. DESIGN: This study examined and analyzed 16 control subjects without any complaints of listening difficulties and 16 patients who had visited the outpatient clinic of the Department of Otolaryngology-Head and Neck Surgery, Tohoku University Hospital, with complaints of listening difficulties, especially in background crowded conditions, despite having relatively good hearing on routine audiograms and speech audiometry. Using five loudspeakers located in front of the subject and at 30° and 60° to the left and right from the front, word intelligibility for the target voice (female talker) presented from one of the loudspeakers in random order with four distractor voices (male talker) was assessed under the following cue conditions: (1) "no additional temporal/directional cue (only talker sex as a cue)"; (2) "fixed temporal cue without directional cue" (white noise bursts [cue sounds] were presented from the five loudspeakers just before word presentation at 500-ms intervals); (3) "directional + variable temporal cues" [cue sounds were presented from the loudspeaker where the next target word would be presented with a variable inter-stimulus interval [ISI] of 500, 1000, 1500, or 2000 ms between the cue sound and word presentation); and (4) "directional + fixed temporal cues" (cue sounds were presented from the loudspeaker where the next target word would be presented with a fixed ISI of 500 ms). RESULTS: The results indicated the following: (1) word intelligibility under distractors was significantly deteriorated in patients with listening difficulties compared with control subjects, although the clinical speech in noise test using the headphone system did not show any significant differences between the two groups; (2) word intelligibility under distractors for patients with listening difficulties was significantly improved with directional cues presented in advance; and (3) under most cue conditions, individual differences in word intelligibility among patients with listening difficulties were significantly correlated with their dichotic listening ability, which is one of the indicators used to assess auditory selective attention ability. CONCLUSIONS: The results of this study indicate the usefulness of the presentation of directional cues for speech comprehension in the cocktail party situation in patients with listening difficulties, as well as the importance of evaluating the degree of listening difficulties spatially in the cocktail party situation.

Synthesis, gene silencing activity, thermal stability, and serum stability of siRNA containing four (S)-5'-C-aminopropyl-2'-O-methylnucleosides (A, adenosine; U, uridine; G, guanosine; and C, cytidine).

Herein, we report the synthesis of (S)-5'-C-aminopropyl-2'-O-methyladenosine and (S)-5'-C-aminopropyl-2'-O-methylguanosine phosphoramidites and the properties of small interfering RNAs (siRNAs) containing four (S)-5'-C-aminopropyl-2'-O-methylnucleosides (A, adenosine; U, uridine; G, guanosine; and C, cytidine). The siRNAs containing (S)-5'-C-aminopropyl-nucleosides at the 3'- and 5'-regions of the passenger strand were well tolerated for RNA interference (RNAi) activity. Conversely, the (S)-5'-C-aminopropyl modification in the central region of the passenger strand decreased the RNAi activity. Furthermore, the siRNAs containing three or four consecutive (S)-5'-C-aminopropyl-2'-O-methylnucleosides at the 3'- and 5'-regions of the passenger strand exhibited RNAi activity similar to that of the corresponding 2'-O-methyl-modified siRNAs. Finally, it was observed that (S)-5'-C-aminopropyl modifications effectively improved the serum stability of the siRNAs, compared with 2'-O-methyl modifications. Therefore, (S)-5'-C-aminopropyl-2'-O-methylnucleosides would be useful for improving the serum stability of therapeutic siRNA molecules without affecting their RNAi activities.

Auditory Subjective-Straight-Ahead Blurs during Significantly Slow Passive Body Rotation.

This paper reports on the deterioration in sound-localization accuracy during listeners' head and body movements. We investigated the sound-localization accuracy during passive body rotations at speeds in the range of 0.625-5 °/s. Participants were asked to determine whether a 30-ms noise stimuli emerged relative to their subjective-straight-ahead reference. Results indicated that the sound-localization resolution degraded with passive rotation, irrespective of the rotation speed, even at speeds of 0.625 °/s.

Isolation of new derivatives of the 20-membered macrodiolide bispolide from Kitasatospora sp. MG372-hF19.

New three macrocyclic diolides, named bispolides C-E (1-3), were isolated from a fermentation broth of the actinomycete strain MG372-hF19, which produces an indole glycoside and leptomycins as we reported previously. The absolute structures of compounds 1-3 were elucidated by NMR and X-ray crystallography. Compounds 1-3 diverge from the known nine bispolides in their different alkylation patterns on the 20-membered macrocyclic diolide skeleton and the side chain in their planar structures. Furthermore, compounds 1-3 exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci and cytotoxic activity against human cancer cell lines. Among them, compound 3 has the most potent biological activities against bacteria and tumor cells. Additionally, using a membrane-potential-sensitive fluorescence probe, we found that compounds 1-3 and elaiophylin have a similar effect on membrane potential in A549 human lung cancer cells.

Loudness functions for patients with functional hearing loss.

OBJECTIVES: To compare the loudness functions (loudness ratings as a function of sound level) obtained from patients diagnosed as having functional hearing loss (FHL) with those for patients with sensorineural hearing loss (SNHL) and healthy volunteers. DESIGN: Loudness functions for a 1000 Hz tone for patients with FHL and SNHL were assessed based on the categorical loudness scaling method. The data were compared with control data obtained in our facilities. STUDY SAMPLE: 18 patients (33 ears) with FHL and 10 patients (19 ears) with SNHL. RESULTS: For patients with SNHL and healthy volunteers, loudness increased progressively with increasing sound level above the audiometric threshold, with no exceptions. However, for about 70% of the patients with FHL, a different type of loudness function was obtained; the thresholds determined from the loudness function, which were defined as the minimum sound levels at which loudness could be judged, were 10 dB or more lower than the audiometric threshold (>10 dB), and/or the loudness ratings were elevated for a sound at the audiometric threshold. CONCLUSIONS: The results support the hypothesis that patients with FHL often make threshold judgments based on a certain loudness.

Estimation of the Acoustic Properties of the Random Packing Structures of Granular Materials: Estimation of the Sound Absorption Coefficient Based on Micro-CT Scan Data.

In this study, the sound absorption properties of randomly packed granular materials were estimated. Generally, it is difficult to construct a general mathematical model for the arrangement of randomly packed granular materials. Therefore, in this study, an attempt was made to estimate the sound absorption coefficient using a theoretical analysis by introducing data from computed tomography (CT) scans, as the tomographic images of CT scans correspond to the slicing and elemental division of packing structures. In the theoretical analysis, the propagation constants and characteristic impedances in the voids were obtained by approximating each tomographic image as a void between two parallel planes. The derived propagation constants and characteristic impedances were then treated as a one-dimensional transfer matrix in the propagation of sound waves, and the transfer matrix method was used to calculate the normal incident sound absorption coefficient. The theoretical value of the sound absorption coefficient was derived using the effective density to which the measured tortuosity was applied. As a result, for the theoretical values considering the tortuosity, in many cases, the theoretical values were close to the measured values. For the theoretical values, when both the surface area and tortuosity were considered, the peak sound absorption frequency moved to a lower frequency and was in general agreement with the measured values.

Theoretical and experimental analyses of acoustic characteristics of fine-grain powder considering longitudinal vibration and boundary layer viscosity.

There was a previous study to derive the sound absorption coefficient of the powder layers comprising powder particles with a diameter of a few tens of µm. According to this previous method, the impact of air viscosity at the boundary layer generated in the pores between the powder particles is neglected. Therefore, precision is not guaranteed when the particle diameter is relatively large or when the density is relatively high. In the present study, to obtain the sound absorption coefficient of the powder layer more accurately, in addition to the above-described longitudinal vibration mode, the energy damping property of the boundary layer viscosity was calculated using the transfer-matrix method. As a result, when the longitudinal vibration mode and boundary layer viscosity were considered, the theoretical value tended to be closer to the experimental value than when only the longitudinal vibration was considered.

Extracellular vesicles shed from gastric cancer mediate protumor macrophage differentiation.

BACKGROUND: Peritoneal dissemination often develops in gastric cancer. Tumor-associated macrophages (TAMs) are present in the peritoneal cavity of gastric cancer patients with peritoneal dissemination, facilitating tumor progression. However, the mechanism by which macrophages differentiate into tumor-associated macrophages in the peritoneal cavity is not well understood. In this study, the interplay between gastric cancer-derived extracellular vesicles (EVs) and macrophages was investigated. METHODS: The association between macrophages and EVs in peritoneal ascitic fluid of gastric cancer patients, or from gastric cancer cell lines was examined, and their roles in differentiation of macrophages and potentiation of the malignancy of gastric cancer were further explored. RESULTS: Immunofluorescent assays of the ascitic fluid showed that M2 macrophages were predominant along with the cancer cells in the peritoneal cavity. EVs purified from gastric cancer cells, as well as malignant ascitic fluid, differentiated peripheral blood mononuclear cell-derived macrophages into the M2-like phenotype, which was demonstrated by their morphology and expression of CD163/206. The macrophages differentiated by gastric cancer-derived EVs promoted the migration ability of gastric cancer cells, and the EVs carried STAT3 protein. CONCLUSION: EVs derived from gastric cancer play a role by affecting macrophage phenotypes, suggesting that this may be a part of the underlying mechanism that forms the intraperitoneal cancer microenvironment.