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Nivolumab, an anti-programmed death-1 (PD-1) receptor monoclonal antibody, has proven effective in treating platinum-resistant metastatic head and neck squamous cell carcinoma. Immune-related adverse events (irAEs) are well-known complications of PD-1 inhibitors. Meanwhile, cytokine release syndrome (CRS), a life-threatening immune-related adverse event, rarely develops due to nivolumab monotherapy. Here, we report a case of a 65-year-old man with squamous cell head and neck carcinoma of an occult primary origin who developed nivolumab-associated late-onset CRS that recurred. The patient was admitted with symptoms of fatigue, fever, hypotension, and respiratory distress. The diagnosis of CRS was supported by the elevated serum levels of interleukin-6 and ferritin, and the patient responded well to high-dose methylprednisolone. CRS recurred during steroid tapering, coinciding with an increased tumor burden; however, it was successfully managed with increased steroid dosing. Early detection and treatment with steroids are essential for the management of CRS.

Objectives Patient-reported outcomes reflecting quality of life (QOL) and hope are essential targets for in-home medical care. This study examined the association between the quality of patient-centred care and both QOL and hope.Design Multicentre, cross-sectional study.Setting Twenty-nine home care clinics in the Tokyo Metropolitan Area, Nara Prefecture and Nagasaki Prefecture in Japan.Participants 200 patients receiving home medical care.Exposure Patient-centredness was measured using the Japanese version of the Primary Care Assessment Tool-Short Form (JPCAT-SF).Outcome measures The primary outcome measures were QOL, assessed using the QOL-Home Care (QOL-HC) scale, and hope, measured using the Health-Related Hope (HR-Hope) scale. Mixed-effects linear models were applied.Results A higher JPCAT-SF total score was associated with a higher QOL-HC score (adjusted mean difference per 10-point increase: 0.28, 95% CI 0.16 to 0.40). Among the JPCAT-SF domains, higher scores in first contact (0.16, 95% CI 0.08 to 0.23), longitudinality (0.20, 95% CI 0.11 to 0.29), comprehensiveness (services available) (0.12, 95% CI 0.03 to 0.20), comprehensiveness (services provided) (0.08, 95% CI 0.01 to 0.15) and community orientation (0.11, 95% CI 0.02 to 0.20) were also associated with higher QOL-HC scores. Similarly, a higher JPCAT-SF total score was associated with a higher HR-Hope score (adjusted mean difference per 10-point increase: 4.8, 95% CI 2.9 to 6.7). Additionally, higher scores in individual JPCAT-SF domains were associated with higher HR-Hope scores: first contact (2.7, 95% CI 1.3 to 4.1), longitudinality (2.5, 95% CI 0.8 to 4.2), coordination (1.2, 95% CI 0.2 to 2.3), comprehensiveness (services available: 1.8, 95% CI 0.5 to 3.2; services provided: 1.3, 95% CI 0.4 to 2.3) and community orientation (1.8, 95% CI 0.5 to 3.1).Conclusions Higher quality patient-centred care is positively associated with enhanced QOL and hope among home medical care patients. Patient-centredness should be strengthened in daily clinical practice.

Background/purpose: Following the COVID-19 pandemic, there were reports of diagnostic delays and a surge in the prevalence of advanced head and neck cancer (HNC). We conducted a retrospective study on the impact of COVID-19 on the number of newly diagnosed HNC among patients who underwent screening at our center to understand the temporal changes. Materials and methods: We investigated the Union for International Cancer Control guidelines-TNM classification, presence of subjective symptoms at the time of consultation, and initial treatment from the medical records of first-time patients with HNC who visited our head and neck surgery department during 2019–2021 and compared them with those before (2019) and after (2020–2021) the pandemic. Results: A total of 1245 patients were included in the study. The number of patients were 437, 417, and 391 in 2019, 2020, and 2021, respectively, indicating a downward trend following the pandemic. When the incidence of early (stage 0–II) and advanced (stage III–IV) HNC cancers was compared, the proportion of patients with early-stage cancer declined. Among them, significant primary tumor progression was observed in T classification. The number of patients with no subjective symptoms at initial diagnosis was decreasing significantly. Conclusion: A decrease in the proportion of HNC patients with early-stage cancer and primary tumor progression was observed after the pandemic in 2020 and 2021. The number of early-stage malignancies may have dropped due to patients’ unwillingness to visit a doctor.

In order to demonstrate the application of terahertz time-domain ellipsometry (THz-TDE) in the characterization of wide-bandgap semiconductors, we studied two zinc oxide (ZnO) single crystals with different conductivities. The optical properties of ZnO samples with low conductivity and high conductivity are both obtained by ellipsometric parameters, while the electrical properties of ZnO sample with high conductivity are well deduced and fitted using the Drude model. These results suggest that THz-TDE can effectively obtain the optical and electrical properties of wide-gap semiconductors and can be used to characterize semiconductors with carrier densities higher than 1016 cm−3.

This study aimed to develop a method to evaluate the quality of bovine in vitro fertilized (IVF) embryos based on gene expression profiling via whole-transcriptome amplification. The expression of 11 developmentally important genes in individual bovine in vivo-derived (IVD) and IVF embryos were examined. Gene expression profiling was conducted by classifying the expression level of each gene in individual embryos as low, medium, or high. The IVF group had a higher (P < 0.01) proportion of embryos with low expression of SOX2, NANOG, and FGF4. In addition, a correlation analysis between the expression levels of each gene in individual embryos demonstrated that the relationship between gene expression differed with respect to IVD and IVF embryos. Our results suggest that the expression profiling of developmentally important genes using IVD embryos as normal controls could be a useful indicator for evaluating the quality of bovine IVF embryos.

BackgroundIn view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC. MethodsThe study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing.ResultsOf 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses. ConclusionNivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.

The flow diverter has been shown to be a safe and effective device for large cerebral aneurysms in the proximal internal carotid artery (ICA). Recently, its indication has been expanded to small- and medium-sized cerebral aneurysms in the distal segment of the ICA. In this study, we report a single-center, retrospective investigation of the safety and efficacy of the Pipeline Flex device to treat these aneurysms. Of the patients who underwent Pipeline implantation for small- and medium-sized ICA aneurysms (12 mm) at our hospital between July 2013 and October 2021, 102 patients with 104 aneurysms were included in this study. The mean age of the patients was 57.7 ± 12.1 years, and 94 (90.4%) were female. The mean aneurysmal dome diameter was 9.2 ± 2.3 mm, the mean neck diameter was 5.3 ± 1.6 mm, and the mean dome-to-neck ratio was 1.8 ± 0.5. Twenty-five patients (24.0%) had incorporated vessels from the aneurysm. Complete occlusion of the aneurysms was obtained in 96 patients (92.3%). There were no cases of parent artery stenosis or major stroke after the procedure. Absence of incorporated vessel from the aneurysm dome and adjunctive coil embolization are statistically significant factors indicating complete occlusion in multivariate analysis. The time to complete occlusion was determined earlier with the use of the Pipeline Shield (p = 0.0386) and with adjunctive coils (p = 0.0025). We showed that Pipeline implantation for small- and medium-sized aneurysms was safe and highly effective.

As of January 2021, the Surpass Streamline (SS) is the most recently approved flow diverter in Japan. A total of 28 Japanese patients, including 9 clinical trial patients, with 28 large or giant unruptured internal carotid artery (ICA) aneurysms, underwent SS embolization at Juntendo University Hospital. Procedural failure occurred in two patients due to the difficulty to navigate the device in the tortuous parent artery. Therefore, 26 patients with 26 aneurysms were available for clinical and anatomical assessments. Patients' mean age was 62.6 years (range 46-86), and 24 patients (92.3%) were female. Mean aneurysm size and neck width were 15.4 mm and 7.7 mm, respectively, with 20 saccular and 6 fusiform aneurysms. Seven aneurysms were symptomatic due to the aneurysmal mass effect. Twenty patients underwent a 6-month follow-up angiography to evaluate the degree of occlusion. Anatomical outcomes were 12 (60%) complete occlusion (CO), 4 (20%) residual neck (RN), and 4 (20%) residual aneurysm. Favorable aneurysm occlusion consisted of CO, and RN was achieved in 16 (80.0%). There were no significant device stenoses. Aneurysmal mass effect improved in one and was unchanged in eight patients. There were three device-related complications, namely, delayed aneurysm rupture, minor ischemic stroke, and device occlusion (11.5%). One patient with minor ischemic stroke fully recovered before 30 days, and our series showed 7.7% risk of major ipsilateral stroke and neurological death at 30 days. The SS embolization for large and giant unruptured ICA aneurysms offers satisfactory anatomical and clinical outcomes with a low risk of device-related complications.

Objective The association between the severity of COVID-19 and gastrointestinal (GI) bleeding is unknown. This study aimed to determine whether the severity of COVID-19 is a risk factor for GI bleeding.Design A multicentre, retrospective cohort study was conducted on hospitalised patients with COVID-19 between January 2020 and December 2021. The severity of COVID-19 was classified according to the National Institute of Health severity classification. The primary outcome was the occurrence of GI bleeding during hospitalisation. The main analysis compared the relationship between the severity of COVID-19 and the occurrence of GI bleeding. Multivariable logistic regression analysis was performed to evaluate the association between the severity of COVID-19 and the occurrence of GI bleeding.Results 12 044 patients were included. 4165 (34.6%) and 1257 (10.4%) patients had severe and critical COVID-19, respectively, and 55 (0.5%) experienced GI bleeding. Multivariable analysis showed that patients with severe COVID-19 had a significantly higher risk of GI bleeding than patients with non-severe COVID-19 (OR: 3.013, 95% CI: 1.222 to 7.427). Patients with critical COVID-19 also had a significantly higher risk of GI bleeding (OR: 15.632, 95% CI: 6.581 to 37.130). Patients with severe COVID-19 had a significantly increased risk of lower GI bleeding (OR: 10.349, 95% CI: 1.253 to 85.463), but the risk of upper GI bleeding was unchanged (OR: 1.875, 95% CI: 0.658 to 5.342).Conclusion The severity of COVID-19 is associated with GI bleeding, and especially lower GI bleeding was associated with the severity of COVID-19. Patients with severe or critical COVID-19 should be treated with caution as they are at higher risk for GI bleeding.

Intracranial germ cell tumors (IGCTs) are rare brain tumors mainly diagnosed in children and young adults. Here, the authors conduct a genome-wide association study for IGCTs, identify a risk locus at BAK1, and characterize its functional consequences.

Although hormonal induction of parturition in cattle results in the successful delivery of healthy calves, the risk of retained fetal membrane is significantly increased. In a previous study, a combination of the long-acting glucocorticoid, triamcinolone acetonide, with a high dose of betamethasone partially normalized the placentomal gene expression during parturition; however, the incidence of retained fetal membrane remained high. This study further explored placentomal dysfunction and aimed to elucidate the mechanism of retained fetal membrane in parturition-induced cows. In this study, transcriptome analysis revealed that enhanced glucocorticoid exposure normalized the expression of a substantial fraction of genes in the cotyledons. In contrast, a significant reduction in the multiple signaling pathway activities, including interferon signaling, was found in the caruncles during induced parturition. Real-time PCR showed that the expression of interferon-tau in the caruncles, but not interferon-alpha or interferon-gamma, was significantly lower in induced parturition than spontaneous parturition. Interferon-stimulated gene expression was also significantly decreased in the caruncles during induced parturition. These results indicate that interferon signaling could be important for immunological control in placentomes during parturition. Additionally, this suggests that interferon-tau might be a pivotal ligand for interferon receptors in the caruncles. This study revealed that peripheral blood leukocytes in prepartum cows transcribed interferon-tau. Macrophage infiltration in the placentome is known to participate in the detachment of the fetal membrane from the caruncle. Thus, this study raised the possibility that immune cells migrating into the caruncles at parturition may act as a source of ligands that activate interferon signaling.

Background: Brenner tumor is a rare epithelial ovarian neoplasm that accounts for 2–3% of all ovarian neoplasms. Herein, we report the first case of thoracic spinal metastasis of recurrent Brenner tumor without local recurrence.Case Description.A 70-year-old female presented with a feeling of abdominal distension. Computed tomography revealed cystic lesions in her bilateral ovaries. Blood examination revealed high CA-125 [74.9 U/ml]. We excised bilateral ovaries, uterus, and omentum. Borderline Brenner tumor was diagnosed [Ki-67 labeling index: 10 %]. Follow-up abdominal echo and CA-125 examination revealed no local recurrence. 26 months later she developed paraplegia. Magnetic resonance imaging revealed tumor in the 5th-9th thoracic vertebra and compression of spinal cord at the 6th thoracic vertebra level. Her paraplegia was progressive. We performed semi-urgent partial resection of tumor and release of spinal cord compression. Spinal metastasis from Brenner tumor was diagnosed [Ki-67 labeling index: 50–60 %]. She received adjuvant radiation of 30 Gy in 10 fractions to the 4th-10th thoracic vertebra. After radiation and rehabilitation, she was discharged home on foot. She received adjuvant radiation and chemotherapy but died 11 months after spinal surgery. An autopsy has not been performed on her, and the cause of death is unknown. Conclusion: We report the first case of thoracic metastasis of recurrent Brenner tumor without local recurrence.

This article has been withdrawn from this issue: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been withdrawn at the request of the editor and publisher. It is now available at https://doi.org/10.1016/j.gore.2022.101120The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error.

Preimplantation genomic selection combined with an in vitro embryo production system is expected as a means of accelerating genetic improvement in cattle. While micromanipulation-based biopsy approaches are often used to collect embryonic cells for genetic testing, they require expensive equipment and sophisticated skills, hindering the adoption of this system. In the present study, to develop a simple method for preimplantation genomic selection using the blastomere separation (BS) technique in bovine in vitro fertilized embryos, we examined the accuracy of single nucleotide polymorphism (SNP) genotyping and optimal cryopreservation method in demi-blastocysts produced by the BS technique. We demonstrated reliable SNP genotyping using DNA derived from demi-blastocysts. We indicated a suitable equilibrium time in vitrification solution for demi-blastocysts and succeeded obtaining pregnancies by the transfer of vitrified demi-blastocysts. In conclusion, our findings suggest that the BS technique provides a simple method for preimplantation genomic selection in bovine in vitro fertilized embryos.

A project of CO2 injection in the Ishikari coal basin (Yubari-shi, Hokkaido, Japan) since 2002 has shown that injection of CO2 into coal seams affected their permeability. Adsorption of CO2 caused swelling of the coal matrix and lowered the permeability of coal seams, probably because of closure of cleats and pores in the coal seams. However, a temporary recovery of permeability was observed after subsequent injection of N2, suggesting that some amount of adsorbed CO2 was replaced by N2 and the closure of cleats and pores were mitigated. However, the changes of mechanical properties of coal in the process are not yet fully understood. In this study, we injected CO2 and N2 into coal specimens recovered from the Ishikari coal basin and observed the changes of coal strength under hydrostatic pressure and temperatures typical of a coal basin. We conducted triaxial compressive strength tests on the coal specimens to clarify the effects of CO2 and N2 on the mechanical properties. Our results are summarized below. 1) We verified that swelling and shrinkage of the coal were associated with adsorption and desorption, respectively, of CO2. 2) The triaxial compressive strength tests showed that injection of CO2 caused decreases of peak strength and Young's modulus. 3) Both coal strength and Young's modulus recovered when previously injected CO2 was replaced by N2.

Abstract Febrile infection‐related epilepsy syndrome (FIRES) is a disease of unknown etiology, characterized by refractory frequent focal seizures, which require prolonged intensive care. We successfully treated a boy with FIRES with anti‐inflammatory and immunosuppressive therapy. This case suggests that an autoimmune mechanism may play a role in the development of FIRES.

The contraction of cardiac and skeletal muscles is regulated by Ca2+ released from the sarcoplasmic reticulum in muscle cells. Here the authors provide molecular insights into Ca2+ regulation of muscle contraction by determining the cryo-EM structures of the human cardiac muscle thin filament in the absence and presence of Ca2+.

Abstract Background Programmed cell death ligand-1 (PD-L1) expression on tumor cells (TCs) is associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy, although its role as a prognostic factor is controversial. This study investigates whether tumoral expression of PD-L1 is a prognostic marker in patients with recurrent and/or metastatic (R/M) HNSCC treated with standard chemotherapy. Methods This retrospective, multicenter, noninterventional study assessed PD-L1 expression on archival R/M HNSCC tissue samples using the VENTANA PD-L1 (SP263) Assay. PD-L1 high was defined as PD-L1 staining of ≥ 25% TC, with exploratory scoring at TC ≥ 10% and TC ≥ 50%. The primary objective of this study was to estimate the prognostic value of PD-L1 status in terms of overall survival (OS) in patients with R/M HNSCC. Results 412 patients (median age, 62.0 years; 79.9% male; 88.2% Caucasian) were included from 19 sites in seven countries. 132 patients (32.0%) had TC ≥ 25% PD-L1 expression; 199 patients (48.3%) and 85 patients (20.6%) had TC ≥ 10% and ≥ 50%, respectively. OS did not differ significantly across PD-L1 expression (at TC ≥ 25% cutoff median OS: 8.2 months vs TC

The present study investigated the effect of autophagy induction and cathepsin B (CTSB) inhibition on developmental competence of poor quality oocytes. Bovine cumulus oocyte complexes (COCs) were classified as good or poor according to their morphology. Autophagy activity was detected in good and poor germinal vesicle (GV) oocytes. Then E-64, a CTSB inhibitor, rapamycin (Rapa), an autophagy inducer, and combined administration was achieved during invitro maturation (IVM) of poor quality COCs followed by detection of autophagy activity. In the next experiment, E-64, Rapa, and E64 + Rapa, were added during IVM to good and poor quality COCs followed by invitro fertilization and culture for 8 days to investigate whether inhibition of CTSB and/or induction of autophagy improve embryonic development and quality. Autophagy activity was significantly lower in poor quality GV oocytes than in good quality ones. E-64, Rapa and E-64 + Rapa treatment during IVM significantly increased autophagy activity in poor quality oocytes. Addition of Rapa in good quality COCs did not increase the blastocyst rate, whereas E-64 increased the blastocyst rate and total cell number (TCN) with decreasing TUNEL-positive cells. In contrast, Rapa treatment in poor quality COCs significantly increased the blastocyst rate and TCN with decreasing TUNEL-positive cells. These results indicate oocyte quality has different responses to intracellular autophagy induction and CTSB activity control by potential autophagy and catabolic status, however, synergetic effect of autophagy induction and CTSB inhibition can increase developmental competence of both good and poor quality COCs, especially rescue effect in poor quality COCs.

Lysosomal cathepsin, in particular cathepsin B (CTSB), plays an important role in implantation, pregnancy, and embryonic development. However, little is known about the mechanism related to the dynamic status of lysosomal cathepsins in bovine oocytes and preimplantation embryos. In the present study, we investigated the dynamics of gene expression, activity, and immunolocalization of CTSB, as well as the activities of lysosome, in bovine oocytes and preimplantation embryos. After gene expression analysis of several cathepsin-related genes, transcript levels of CTSB, CTSD and CTSZ were highest in Metaphase II (MII) oocytes followed by a significant decrease from the 8-cell embryo stage. Activity of CTSB showed a significant increase in 1-cell and morula stage embryos. Lysosomal activity was also significant higher in 1-cell and morula stages, which was consistent with CTSB activities. However, immunolocalization of CTSB did not show the similar pattern of CTSB and lysosomal activities. We also found significantly higher expression levels of CTSB transcript in the trophectoderm (TE) compared to inner cell mass (ICM), whereas activity and immunolocalization of CTSB showed an opposite pattern, i.e. significantly higher in ICM than TE. These patterns were confirmed by the same analysis using separated ICM and TE. Our results suggest that lysosomal CTSB has a pivotal role during embryonic development and differentiation, especially fertilization and the differentiation period.

In bovine placentomes, the inflammatory response is considered important for the detachment of the fetal membrane from the caruncle after parturition. Glucocorticoids, a trigger of the onset of parturition, facilitate functional maturation of placentomes via prostaglandin (PG) and estrogen production in cattle. This study investigated how exogeneous glucocorticoids, which exert immunosuppressive effects, affect placental inflammation at parturition. Placentomes were collected immediately after spontaneous or induced parturition. Parturition was conventionally induced using PGF2α or dexamethasone or with a combination of triamcinolone acetonide and high-dose betamethasone (TABET treatment). Polymerase chain reaction (PCR) array analysis indicated that 9/13 C–C motif chemokine ligands (CCLs) were upregulated > two-fold in spontaneous parturition, with CCL2 and CCL8 being highly expressed. The expressions of CCL2, CCL8, C–C motif chemokine receptor 1 (CCR1), and CCR5 in caruncles were significantly higher in spontaneous parturition than in induced parturition. Although the clinical dose of dexamethasone did not influence the expression of these CCLs and CCRs, TABET treatment increased CCR1 expression. CCL8, CCR1, CCR2, and CCR5 were localized in the caruncular epithelial cells. CCR2 was also localized in the epithelial cells of the cotyledonary villi. This study is the first report to reveal the disruption in CCL and CCR expression in bovine placentomes at induced parturition. Enhanced glucocorticoid exposure for the induction of parturition may upregulate CCR1 expression in placentomes, but the treatment does not adequately promote CCL expression. Additionally, immunohistochemistry suggested that the CCL–CCR system is involved in the functional regulation of maternal and fetal epithelial cells in placentomes at parturition.

MgtE is a Mg2+ channel conserved in organisms ranging from prokaryotes to eukaryotes, including humans, and plays an important role in Mg2+ homeostasis. The previously determined MgtE structures in the Mg2+-bound, closed-state, and structure-based functional analyses of MgtE revealed that the binding of Mg2+ ions to the MgtE cytoplasmic domain induces channel inactivation to maintain Mg2+ homeostasis. There are no structures of the transmembrane (TM) domain for MgtE in Mg2+-free conditions, and the pore-opening mechanism has thus remained unclear. Here, we determined the cryo-electron microscopy (cryo-EM) structure of the MgtE-Fab complex in the absence of Mg2+ ions. The Mg2+-free MgtE TM domain structure and its comparison with the Mg2+-bound, closed-state structure, together with functional analyses, showed the Mg2+-dependent pore opening of MgtE on the cytoplasmic side and revealed the kink motions of the TM2 and TM5 helices at the glycine residues, which are important for channel activity. Overall, our work provides structure-based mechanistic insights into the channel gating of MgtE.

Preimplantation genomic selection using genomic estimated breeding values (GEBVs) based on single nucleotide polymorphism (SNP) genotypes is expected to accelerate genetic improvement in cattle. To develop a preimplantation genomic selection system for carcass traits in Japanese Black cattle, we investigated the accuracy of genomic evaluation of carcass traits using biopsied embryonic cells (Experiment 1); we also performed an empirical evaluation for embryo transfer (ET) of vitrified GEBV-evaluated blastocysts to assess the efficiency of the preimplantation genomic selection system (Experiment 2). In Experiment 1, the mean call rate for SNP genotyping using approximately 15 biopsied cells was 98.1 ± 0.3%, whereas that for approximately 5 biopsied cells was 91.5 ± 2.4%. The mean concordance rate for called genotypes between ~15-cell biopsies and the corresponding biopsied embryos was 99.9 ± 0.02%. The GEBVs for carcass weight, ribeye area, and marbling score calculated from ~15-cell biopsies closely matched those from the corresponding calves produced by ET. In Experiment 2, a total of 208 in vivo blastocysts were biopsied (~15-cell) and the biopsied cells were processed for SNP genotyping, where 88.5% of the samples were found to be suitable for GEBV calculation. Large variations in GEBVs for carcass traits were observed among full-sib embryos and, among the embryos, some presented higher GEBVs for ribeye area and marbling score than their parents. The conception rate following ET of vitrified GEBV-evaluated blastocysts was 41.9% (13/31). These findings suggest the possible application of preimplantation genomic selection for carcass traits in Japanese Black cattle.

Abstract Background Metachronous cancer in patients with head and neck cancer (HNC) is common and is associated with a poor prognosis. We aimed to evaluate the incidence of metachronous cancer at different sites according to age at diagnosis of index HNC. Methods We collected data on 2011 patients with oral cancer, oropharynx cancer, hypopharyngeal cancer, and laryngeal cancer as index cancers using the Osaka International Cancer Institute Cancer Registry database between 2005 and 2016. Among these, we analyzed 1953 patients after excluding 5 patients who were not followed-up and 53 patients with simultaneous multiple index cancers. We evaluated the cumulative incidence of metachronous cancer in the esophagus, lung, and other sites according to age at diagnosis of the index HNC using the Kaplan–Meier method. Multivariate logistic regression analysis was performed to identify factors that influenced the incidence of metachronous cancers following HNC. Results The cumulative incidence of metachronous esophageal cancer in young patients (

Optimal regimens using recent radiotherapy (RT) equipment for bleeding gastric cancer (GC) have not been fully investigated yet. We retrospectively reviewed the clinical data of 20 patients who received RT for bleeding GC in our institution between 2016 and 2021. Three-dimensional conformal RT was performed. The effectiveness of RT was evaluated by the mean serum hemoglobin (Hb) level and the number of transfused red blood cell (RBC) units 1 month before and after RT. The median first radiation dose was a BED of 39.9 Gy. The treatment success rate was 95% and the rebleeding rate was 10.5%. There was a significant increase in the mean Hb level (8.0 ± 1.1 vs. 9.8 ± 1.3 g/dL, p = 0.01), and a significant decrease in the mean number of transfused RBC units (6.8 ± 3.3 vs. 0.6 ± 1.5 units, p < 0.01). Severe toxicity was observed in two patients (anorexia [n = 1] and gastrointestinal [GI] perforation [n = 1]). Reirradiation was attempted in three patients (for hemostasis [n = 2] and for mass reduction [n = 1]). The retreatment success rate for rebleeding was 100%. GI perforation occurred in two patients who had received hemostatic reirradiation. Palliative RT for bleeding GC using recent technology had excellent efficacy. However, it may be associated with a risk of GI perforation.

Dural arteriovenous fistula (DAVF) of the anterior condylar confluence (ACC) is a rare entity accounting for about 3.6% of all DAVFs. We report on a 63-year-old male patient who presented with pulsatile tinnitus. Angiography revealed a DAVF supplied mainly by neuromeningeal branches of bilateral ascending pharyngeal arteries and draining into the ACC. Transvenous transjugular coil embolization was performed resulting in complete obliteration of the fistula and resolution of the symptoms. Due to the complexity of this venous structure at the skull base, detailed angiographic study is crucial for proper therapeutic planning and management of the patient. We here discuss the clinico-radiological features and various treatment modalities of the ACC DAVF.

The bacterial flagellum is a motile organelle that enables bacterial movement. Here the authors explain how the structurally similar flagellum components FlgG and FlgE can give rise to distinct macrostructures—the rod and hook—through subtle differences in domain orientation attributable to a short N-terminal insertion in FlgG.

The cyclic association and dissociation of myosin with actin filament is regulated by ATP binding and hydrolysis cycles. Here the authors report the structure of mammalian skeletal muscle actomyosin rigour complex that provides insights into the ATPase-coupled reaction cycle of actomyosin.

Objective/background: The prevalence of pulmonary nontuberculous mycobacterial (pNTM) disease, including Mycobacterium avium complex (MAC), varies widely according to geographic region. However, the factors that influence regional variations in pNTM disease prevalence remain unknown. This study was undertaken to examine whether environmental or occupational factors or host traits could influence regional variations in pNTM disease prevalence. Methods: We collected laboratory data on pulmonary tuberculosis (pTB) and pNTM from two hospitals in the West Harima area of Japan and five hospitals in Kyoto City, Japan from 2012 to 2013. We estimated microbiological pNTM disease prevalence by multiplying all pTB cases in each area with the ratio of pNTM cases and pTB cases at the survey hospitals in each area. We administered a standardized questionnaire to 52 patients and 120 patients with pulmonary MAC (pMAC) disease at Ako City Hospital and Kyoto University Hospital, respectively. Results: The estimated prevalence of microbiological pNTM disease in the West Harima area (85.4/100,000 population-years) was significantly higher than that observed in Kyoto City (23.6/100,000 population-years; p < .001). According to multiple logistic regression analysis, in Ako City Hospital, primary (activities directly related to natural resources) and secondary industries (construction, mining, and manufacturing primary industry produce; odds ratio [OR] = 4.79; 95% confidence interval [CI] = 1.49−14.0; p = .007) and soil exposure (OR = 13.6; 95% CI = 4.94−45.26; p < .001) were associated with pMAC disease. Conclusion: Environmental factors, both industrial structures associated with occupational dust and environmental soil exposure, could influence the regional variations in pNTM disease prevalence.