Endobronchial spread of adenocarcinoma is a distinct pattern of invasion and associated with inferior clinical outcomes in lung adenocarcinoma.

AIM: The spread of lung adenocarcinoma cells into the bronchi and bronchioles is not well documented. We termed this histological finding "endobronchial spreading of adenocarcinoma" (EBSA) and investigated its prevalence and clinical significance. METHODS AND RESULTS: We reviewed 320 resected specimens from patients diagnosed with invasive adenocarcinoma, and EBSA was observed in 144 patients (45%). EBSA was significantly associated with advanced pathological stage, higher histological grade, larger tumour invasion, lymphovascular infiltration, and spread through air spaces. Patients with EBSA had significantly shorter relapse-free survival (RFS) and cancer-specific survival (CSS) in univariate analysis (P < 0.001). In a subgroup analysis of patient with small-sized (invasion size ≤30 mm) adenocarcinoma in the localized stage, EBSA was an independent inferior prognostic indicator in multivariate analysis. In a subgroup analysis of patients with small-sized Grade 1 nonmucinous adenocarcinoma (n = 61), EBSA was observed in 11 patients, and the presence of EBSA was associated with significantly shorter RFS and CSS (P = 0.026 and P = 0.001, respectively). CONCLUSION: Our results demonstrated that EBSA is a significant risk factor for disease recurrence and cancer-related deaths. EBSA can be regarded as a distinctive pattern of invasion and its recognition can be beneficial in the diagnosis of lung adenocarcinoma.

Recent treatment and prognosis in 643 patients with extramammary Paget's disease.

Information about extramammary Paget's (EMPD) treatment is limited because of the rarity of the disease. The prognosis differs between in situ EMPD and invasive EMPD; therefore, therapy should be planned according to the disease stage. We collected data on 643 EMPD cases treated between 2015 and 2019 in Japan and assessed recent trends in EMPD treatment and prognosis based on the EMPD-oriented TNM staging. Among the 643 patients, 317 had stage 0 (49.3%), 185 had stage I (28.8%), 51 had stage II (7.9%), 18 had stage IIIA (2.8%), 48 had stage IIIB (7.5%) and 24 had stage IV (3.7%) disease. Each stage showed a distinct survival curve, with the exception of stages II and IIIA. Curative surgery was most common in patients with stage 0-III disease. Chemotherapy was the first-line therapy, mainly in patients with stage IIIB and IV disease, most commonly with docetaxel (DTX), followed by DTX + tegafur gimeracil oteracil potassium (TS-1) and TS-1. Patients with local disease exhibited a 4.4% recurrence rate. Univariate analysis revealed no prognostic differences according to age, sex or primary tumour site. SLNB was not related to disease-specific survival. In multivariate analysis, female sex significantly predicted local relapse in stage 0-I (HR 3.09; 95% CI, 1.13-8.43), and initial treatment with curative surgery was significantly protective in terms of disease-specific survival in stage II-IIIA (HR, 0.17; 95% CI, 0.04-0.71) and stage IIIB-IV (HR 0.16; 95% CI, 0.05-0.51). Further clinical studies are needed to improve the prognosis of patients with stage II-IV EMPD.

Observation of the Superstructure in Fe5-xGeTe2 by X-ray Fluorescence Holography.

Fe5-xGeTe2 is a two-dimensional van der Waals material that exhibits ferromagnetic order with a high Curie temperature (TC) of around room temperature. In addition to TC, two magnetic transitions occur with decreasing temperature, and a charge-ordered state is observed at low temperatures. We employed Ge Kα X-ray fluorescence holography (XFH) for Fe5-xGeTe2 to directly investigate the local structure in the charge-ordered state, i.e., the 3×3 superstructure. The Ge Kα XFH results revealed local atomic structures around the Ge atom, thus clarifying the simultaneous locations and arrangements of the Te, Fe, and Ge atoms. The atomic positions relative to the Ge atom are useful for understanding the coexistence of the ideal 1 × 1 structure and 3×3 superstructure found in the charge-ordered state.

Pressure Dependence of the Structural and Superconducting Properties of the Bi-Based Superconductor Bi2Pd3Se2.

The structural and superconducting properties of the Bi-based compound Bi2Pd3Se2 were investigated over a wide pressure range. The prepared Bi2Pd3Se2 sample was a superconductor with a superconducting transition temperature, Tc, of approximately 3.0 K, which differed from a previous report (Tc of less than 1.0 K). At ambient pressure, the powder X-ray diffraction (XRD) pattern of the Bi2Pd3Se2 sample was consistent with that previously reported for Bi2Pd3Se2. The Rietveld method was used to refine the crystal structure, which had a space group of C2/m (No. 12), as reported previously. This compound showed no clear anomaly due to the charge-density-wave (CDW) transition, as seen from the temperature dependence of magnetic susceptibility. However, the temperature dependence of electrical resistivity indicated a clear anomaly, presumably because of the CDW transition in the low-pressure range; the CDW transition temperature was approximately 230 K. The XRD patterns of the Bi2Pd3Se2 sample were measured at 0.160-22.7 GPa, and the patterns were well analyzed by both the Le Bail and Rietveld refinement methods, showing no structural phase transitions in the above pressure range. The pressure dependence of Tc of Bi2Pd3Se2 was recorded based on the temperature dependence of the electrical resistance, which showed an almost constant Tc at 0-13.7 GPa, and the Tc-pressure (p) behavior was fully discussed.

Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant.

In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.

Characterization of carotid plaques using chemical exchange saturation transfer imaging.

PURPOSE: The preoperative assessment of carotid plaques is necessary to render revascularization safe and effective. The aim of this study is to evaluate the usefulness of chemical exchange saturation transfer (CEST)-MRI, particularly amide proton transfer (APT) imaging as a preoperative carotid plaque diagnostic tool. METHODS: We recorded the APT signal intensity on concentration maps of 34 patients scheduled for carotid endarterectomy. Plaques were categorized into group A (APT signal intensity ≥ 1.90 E-04; n = 12) and group B (APT signal intensity < 1.90 E-04; n = 22). Excised plaques were subjected to histopathological assessment and, using the classification promulgated by the American Heart Association, they were classified as intraplaque hemorrhage-positive [type VI-positive (tVI+)] and -negative [no intraplaque hemorrhage (tVI-)]. RESULTS: Of the 34 patients, 22 (64.7%) harbored tVI+- and 12 (35.3%) had tVI- plaques. The median APT signals were significantly higher in tVI+- than tIVI- patients (2.43 E-04 (IQR = 0.98-4.00 E-04) vs 0.54 E-04 (IQR = 0.14-1.09 E-04), p < .001). Histopathologically, the number of patients with tVI+ plaques was significantly greater in group A (100%, n = 12) than group B (45%, n = 22) (p < .01). The number of symptomatic patients or asymptomatic patients with worsening stenosis was also significantly greater in group A than group B (75% vs 36%, p < .01). CONCLUSION: In unstable plaques with intraplaque hemorrhage and in patients with symptoms or progressive stenosis, the ATP signals were significantly elevated. CEST-MRI studies has the potential for the preoperative assessment of the plaques' characteristics.

Constipation in patients with motor neuron disease: A retrospective longitudinal study.

Background: Constipation has been recently recognized as a complication associated with motor and autonomic dysfunction in patients with motor neuron disease (MND), typified by amyotrophic lateral sclerosis (ALS). However, the long-term characteristics of constipation remain unclear in patients with MND. We longitudinally investigated the prevalence and risk factors of constipation in a consecutive cohort of patients with MND. Methods: Data from Japanese patients with MND enrolled in a single-center registry from June 2017 to December 2021 were retrospectively investigated. The diagnosis of ALS was based on the updated Awaji criteria, and other MND subtypes were also included. The presence or absence of constipation symptoms was determined by referring to the Rome III criteria. The clinical backgrounds and symptoms of patients with and without constipation were compared. Results: Among 155 consecutive patients (female, 63; age, 66.5 ± 12.4 years), 30.3% had constipation at diagnosis and 52.9% after a median follow-up of 18 months. Univariate analysis showed that female sex, use of tracheostomy and invasive ventilation, and delivery of enteral nutrition were more frequent in the constipation group. The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale score was significantly lower in the constipation group, especially for the sub-items related to physical motor function. Multivariate analysis showed that the use of enteral nutrition was an independent risk of constipation, with an odds ratio of 3.69 (95% CI, 1.49-9.17; p = 0.005). Conclusion: Constipation had a high prevalence in patients with MND with impaired motor function. Controlling defecation is important in patients with MND, especially during enteral nutrition.

Moyamoya Syndrome: Differential Diagnosis in Patients With Central Nervous System Symptoms and Hyperthyroidism.

Moyamoya syndrome, known as secondary moyamoya disease, is associated with various primary illnesses, such as brain tumor, meningitis, autoimmune disease, and thyrotoxicosis, and their relations are not clear. We report a rare case of moyamoya syndrome in a patient with Graves' disease. An 18-year-old woman was admitted to our hospital due to convulsions. She had symptoms of palpitations and fatiguability for half a year and transient numbness in her left upper extremity and dysarthria for a month. In physical findings, tachycardia and diffuse thyroid swelling were noted. A blood test revealed thyrotoxicosis and antithyroid antibody, and a diagnosis of Graves' disease was obtained. Brain magnetic resonance imaging (MRI) showed bilateral internal carotid artery occlusion. We finally diagnosed the patient with moyamoya syndrome caused by Graves' disease. Moyamoya disease or syndrome can cause symptoms like a stroke, sometimes requiring neurosurgical treatment. In our case, the therapy for Graves' disease resolved the symptoms. When diagnosing moyamoya disease, it is necessary to confirm whether there are any background diseases, such as Graves' disease.

Adjusting effective multiplicity ( M eff ) for family-wise error rate in functional near-infrared spectroscopy data with a small sample size.

Significance: The advancement of multichannel functional near-infrared spectroscopy (fNIRS) has enabled measurements across a wide range of brain regions. This increase in multiplicity necessitates the control of family-wise errors in statistical hypothesis testing. To address this issue, the effective multiplicity ( M eff ) method designed for channel-wise analysis, which considers the correlation between fNIRS channels, was developed. However, this method loses reliability when the sample size is smaller than the number of channels, leading to a rank deficiency in the eigenvalues of the correlation matrix and hindering the accuracy of M eff calculations. Aim: We aimed to reevaluate the effectiveness of the M eff method for fNIRS data with a small sample size. Approach: In experiment 1, we used resampling simulations to explore the relationship between sample size and M eff values. Based on these results, experiment 2 employed a typical exponential model to investigate whether valid M eff could be predicted from a small sample size. Results: Experiment 1 revealed that the M eff values were underestimated when the sample size was smaller than the number of channels. However, an exponential pattern was observed. Subsequently, in experiment 2, we found that valid M eff values can be derived from sample sizes of 30 to 40 in datasets with 44 and 52 channels using a typical exponential model. Conclusions: The findings from these two experiments indicate the potential for the effective application of M eff correction in fNIRS studies with sample sizes smaller than the number of channels.

Comparison of Cervical Pedicle Screw Placement Accuracy With Robotic Guidance System Versus Image Guidance System Using Propensity Score Matching.

STUDY DESIGN: A retrospective study. OBJECTIVE: To compare the accuracy of cervical pedicle screw (CPS) placement using a robotic guidance system (RGS) with that of using an image guidance system (IGS; navigation system) through propensity score matching. BACKGROUND: The RGS may provide accurate CPS placement, which may outperform IGS. However, no study has directly compared the accuracy of CPS placement with the RGS to that with the IGS. PATIENTS AND METHODS: We retrospectively reviewed the data of patients who had undergone cervical fusion surgery using CPS with the RGS or IGS. To adjust for potential confounders (patient demographic characteristics, disease etiology, and registration material), propensity score matching was performed, creating robotic guidance (RG) and matched image guidance (IG) groups. The accuracy of CPS placement from C2 to C6, where the vertebral artery runs, was evaluated on postoperative computed tomography images according to the Neo classification (grade 0 to grade 3). Furthermore, the intraoperative CPS revisions and related complications were examined. RESULTS: Using propensity score matching, 22 patients were included in the RG and matched groups each, and a total of 95 and 105 CPSs, respectively, were included in the analysis. In both the axial and sagittal planes, the clinically acceptable rate (grades 0 + 1) of CPS placement did not differ between the RG and matched IG groups (97.9% vs 94.3% and 95.8% vs 96.2%, respectively). The incidence of CPS revision was similar between the groups (2.1% vs 2.9%), and no CPS-related complications were documented. Meanwhile, the incidence of lateral breach (grades 1 + 2 + 3) was significantly lower in the RG group than in the matched IG group (1.1% vs 7.7%, P= 0.037). CONCLUSION: The RGS and IGS can equally aid in accurate and safe CPS placement in clinical settings. Nonetheless, RGS can further reduce the lateral breach, compared with IGS.

Changes in fecal microbiota during estrous cycle in healthy thoroughbred mares.

Gut microbiota plays a crucial role in various physiological processes, including the regulation of the reproductive system and steroid sex hormones. Throughout the normal estrous cycle of healthy mares, the levels of estradiol-17ß (E2) and progesterone (P4) in the blood exhibit periodic changes. To investigate the relationship between cyclic changes in steroid sex hormones and the gut microbiome of mares, we analyzed the fecal microbiota composition in healthy mares during the typical estrous cycle. Blood and fecal samples from five healthy mares were collected, E2 and P4 levels in serum were analyzed using radioimmunoassay (RIA), and the gut microbiome was analyzed by 16S rRNA sequencing. The overall richness and composition of the gut microbiota remained relatively stable during the normal estrous cycle in mares. The Linear Discriminant Analysis Effect Size analysis of the microbial composition during the follicular and luteal phases identified the Rhodococcus genus as differentially abundant. These findings indicate that the mare's gut microbiota's significant composition remains consistent throughout the estrous cycle. At the same time, specific low-abundance pathogenic bacteria exhibit changes that align with sexual hormonal fluctuations.

Downregulation of Histone H3.3 Induces p53-Dependent Cellular Senescence in Human Diploid Fibroblasts.

Cellular senescence is an irreversible growth arrest that acts as a barrier to cancer initiation and progression. Histone alteration is one of the major events during replicative senescence. However, little is known about the function of H3.3 in cellular senescence. Here we found that the downregulation of H3.3 induced growth suppression with senescence-like phenotypes such as senescence-associated heterochromatin foci (SAHF) and ß-galactosidase (SA-ß-gal) activity. Furthermore, H3.3 depletion induced senescence-like phenotypes with the p53/p21-depedent pathway. In addition, we identified miR-22-3p, tumor suppressive miRNA, as an upstream regulator of the H3F3B (H3 histone, family 3B) gene which is the histone variant H3.3 and replaces conventional H3 in active genes. Therefore, our results reveal for the first time the molecular mechanisms for cellular senescence which are regulated by H3.3 abundance. Taken together, our studies suggest that H3.3 exerts functional roles in regulating cellular senescence and is a promising target for cancer therapy.

Greater cervical kyphosis during flexion increases the risk of kyphotic deformity after laminoplasty in patients with cervical spondylotic myelopathy.

Kyphotic deformity following the loss of cervical lordosis can lead to unfavourable neurological recovery after cervical laminoplasty (CLP); therefore, it is essential to identify its risk factors. Recent studies have demonstrated that the dynamic parameters of the cervical spine, based on baseline flexion/extension radiographs, are highly useful to estimate the loss of cervical lordosis after CLP. However, it remains unclear whether such dynamic parameters can predict kyphotic deformity development after CLP. Hence, the present study aimed to investigate whether the dynamic parameters could predict kyphotic deformity in patients with cervical spondylotic myelopathy (CSM) after CLP. This retrospective study included 165 patients, consisting of 10 and 155 patients with and without cervical kyphosis of C2-C7 angle ≤ -10° at the final follow-up period, respectively. Among the static and dynamic parameters of the cervical spine, greater cervical kyphosis during flexion (fC2-C7 angle) demonstrated the best discrimination between these two cohorts, with an optimal cutoff value of -27.5°. Meanwhile, greater gap range of motion (gROM = flexion ROM - extension ROM ) had the highest ability to predict a loss of ≥ 10° in C2-C7 angle after CLP, with an optimal cutoff value of 28.5°. This study suggests that in patients with CSM, fC2-C7 angle ≤ -25° on baseline radiographs is a potential risk for kyphotic deformity after CLP. In clinical practice, the patients with this criterion (fC2-C7 angle ≤ -25°) along with gROM ≥ 30° are at high risk of developing significant kyphotic deformity after CLP.

Influence of cranium orientation on cervical sagittal alignment during radiographic examination: a radiographic analysis.

BACKGROUND CONTEXT: During the radiographic examination, the cranium orientation varies not only individually but also within the same subject, in different imaging sessions. Knowing how changes in the orientation of the cranium influences cervical sagittal alignment during the radiographic examination of the cervical spine can aid clinicians in the accurate evaluation for cervical sagittal alignment in clinical practice. PURPOSE: To radiographically examine the influence of cranium orientation on cervical sagittal alignment during radiographic examination in an asymptomatic cohort. STUDY DESIGN: A prospective radiographic study. PATIENT SAMPLE: Eighty asymptomatic volunteers (mean age, 40.4 years; 50.0% male) were enrolled. OUTCOME MEASURES: Cervical sagittal parameters including the regional slope (C1 slope, C2 slope, C5 slope, C7 slope, and T1 slope), Cobb angle (O-C1 angle, C1-C2 angle, C2-C5 angle, C5-C7 angle, and C7-T1 angle), and cranial/cervical offset (sella turcica tilt [ST tilt] and C2 tilt). METHODS: In all participants, standing lateral radiographs of the cervical spine were taken in three forward-gazing positions: anteverted-cranium (AC) position; neutral-cranium (NC) position; and retroverted-cranium (RC) position. Cervical sagittal parameters, including the regional slope, Cobb angle, and cranial/cervical offset, in these three positions were statistically compared. RESULTS: The C1 and C2 slopes were anteverted and retroverted in the AC and RC positions, respectively, compared to those in the NC position. The C5 slope, C7 slope, and T1 slope were constant among the three positions. In O-C2 and C2-C5, statistically significant differences in the regional Cobb angles were identified among the three positions; however, there were no significant differences in the C5-C7 or C7-T1 segments. Cranial and cervical offsets of ST tilt and C2 tilt increased and decreased when the cranium was anteverted and retroverted, respectively. CONCLUSIONS: The current study suggests that the adjustment of the cranium orientation when taking cervical spine radiographs is mainly controlled at the upper cervical spine of the O-C2 segment in an asymptomatic cohort. On radiograph, alignment in the upper cervical segment of O-C2 changes; accordingly, the middle cervical segment of C2-C5 can change during the adjustment of cranium orientation. However, alignment in the lower cervical segment of C5-C7 and the cervicothoracic junction of C7-T1 remains constant. Further, cranial/cervical offset increases and decreases when the cranium is anteverted and retroverted, respectively. Our results can help the accurate evaluation of cervical sagittal alignment on plain radiographs in clinical practice.

Artificial intelligence-based image-domain material decomposition in single-energy computed tomography for head and neck cancer.

PURPOSE: While dual-energy computed tomography (DECT) images provide clinically useful information than single-energy CT (SECT), SECT remains the most widely used CT system globally, and only a few institutions can use DECT. This study aimed to establish an artificial intelligence (AI)-based image-domain material decomposition technique using multiple keV-output learning of virtual monochromatic images (VMIs) to create DECT-equivalent images from SECT images. METHODS: This study involved 82 patients with head and neck cancer. Of these, the AI model was built with data from the 67 patients with only DECT scans, while 15 patients with both SECT and DECT scans were used for SECT testing. Our AI model generated VMI50keV and VMI100keV from VMI70keV equivalent to 120-kVp SECT images. We introduced a loss function for material density images (MDIs) in addition to the loss for VMIs. For comparison, we trained the same model with the loss for VMIs only. DECT-equivalent images were generated from SECT images and compared with the true DECT images. RESULTS: The prediction time was 5.4 s per patient. The proposed method with the MDI loss function quantitatively provided more accurate DECT-equivalent images than the model trained with the loss for VMIs only. Using real 120-kVp SECT images, the trained model produced precise DECT images of excellent quality. CONCLUSION: In this study, we developed an AI-based material decomposition approach for head and neck cancer patients by introducing the loss function for MDIs via multiple keV-output learning. Our results suggest the feasibility of AI-based image-domain material decomposition in a conventional SECT system without a DECT scanner.

Comparison of Postoperative Respiratory Function Between Patients After Thoracoscopic and Open Lobectomy.

Purpose: This study aimed to compare respiratory functions of patients after thoracoscopic lobectomy (TS) with those after thoracotomy (TR). Methods: This retrospective study was conducted in two centers, one of which adapted TS as a standard procedure in 2009 and the other performs it via TR. Data on patients who underwent lobectomy for congenital lung disease between 2009 and 2021 and underwent pulmonary function test (spirometry) were collected. Results: Ten patients underwent TS and 36 underwent TR. Distribution based on sex, prenatal diagnosis, pathological diagnosis, and resected lobe were similar between the two groups. The median [interquartile range] age at procedure in the TR group was significantly smaller than that in the TS group (13 [11-18] months versus 38 [13-79] months, P = .03). The procedure duration in the TR group was significantly shorter than that in the TS group (230 [171-264] minutes versus 264 [226-420] minutes, P = .02). Pulmonary function test was conducted at the age of eight in both groups, but the interval between the procedure, and the test was significantly shorter in the TS group (TR: 7 [5-8] years versus TS: 5 [2-7] years, P = .03). The ratio of forced vital capacity compared to predicted one (TR: 86.6 [76.6-95.3] versus TS: 88.7 [86.8-89.1], P = .58) and the ratio of forced expiratory volume in 1 second against that predicted (TR: 84.0 [80.5-88.7] versus TS: 88.7 [86.8-89.1], P = .08) were not significantly different between the two groups. Conclusions: Although TR was performed earlier than TS, respiratory function was similar between the two groups.

Alpha-glycosyl isoquercitrin alleviates subchronic social defeat stress-induced depression symptoms by modulating the microbiota-gut-brain axis in mice.

AIMS: Increasing evidence suggests a link between gut microbial dysbiosis and the pathogenesis of depression. Alpha-glycosyl isoquercitrin (AGIQ), consisting of isoquercitrin and its glycosylated quercetin, has beneficial effects on the gut microbiome and brain function. Here, we detected the potential antidepressant impact of a four-week administration of AGIQ and its underlying mechanisms using a mouse model of depression. MAIN METHODS: Male C57BL/6 mice were orally administered AGIQ (0.05 % or 0.5 % in drinking water) for 28 days; subchronic social defeat stress was performed in the last 10 days. Behavior tests were conducted to assess anxiety and depressive-like behaviors. Additionally, evaluations encompassed 5-hydroxytryptamine (5-HT) levels, the gut microbiota composition, lipopolysaccharide (LPS) concentrations, short-chain fatty acids levels, and intestinal barrier integrity changes. KEY FINDINGS: AGIQ significantly alleviated depression-like behaviors and increased hippocampal 5-HT levels. Further, AGIQ mitigated stress-induced gut microbial abnormalities and reduced the levels of LPS in the serum, which affected the relative gene expression levels of 5-HT biosynthesis enzymes in vitro. Furthermore, AGIQ reversed the reduced butyrate levels in cecal contents and improved the impaired intestinal barrier by increasing the expression of colonic zonula occluden-1 (ZO-1) and occludin, thereby decreasing LPS leakage. SIGNIFICANCE: Our results suggest that AGIQ could improve stress-induced depression by regulating the gut microbiome, which inhibits LPS production and maintains the gut barrier. This is the first report on the potential effect of AGIQ on depression via the gut microbiota-brain axis, shedding new light on treatment options.

Comparing interplay effects in scanned proton therapy of lung cancer: Free breathing with various layer and volume rescanning versus respiratory gating with different gate widths.

PURPOSE: We investigated interplay effects and treatment time (TT) in scanned proton therapy for lung cancer patients. We compared free-breathing (FB) approaches with multiple rescanning strategies and respiratory-gating (RG) methods with various gating widths to identify the superior irradiation technique. METHODS: Plans were created with 4/1, 2/2, and 1/4 layered/volume rescans of FB (L4V1, L2V2, and L1V4), and 50%, 30%, and 10% gating widths of the total respiratory curves (G50, G30, and G10) of the RG plans with L4V1. We calculated 4-dimensional dynamic doses assuming a constant sinusoidal curve for six irradiation methods. The reconstructed doses per fraction were compared with planned doses in terms of dose differences in 99% clinical-target-volume (CTV) (ΔD99%), near-maximum dose differences (ΔD2%) at organs-at-risk (OARs), and TT. RESULTS: The mean/minimum CTV ΔD99% values for FB were -1.0%/-4.9%, -0.8%/-4.3%, and -0.1%/-1.0% for L4V1, L2V2, and L1V4, respectively. Those for RG were -0.3%/-1.7%, -0.1%/-1.0%, and 0.0%/-0.5% for G50, G30, and G10, respectively. The CTV ΔD99% of the RGs with less than 50% gate width and the FBs of L1V4 were within the desired tolerance (±3.0%), and the OARs ΔD2% for RG were lower than those for FB. The mean TTs were 90, 326, 824, 158, 203, and 422 s for L4V1, L2V2, L1V4, G50, G30, and G10, respectively. CONCLUSIONS: FB (L4V1) is the most efficient treatment, but not necessarily the optimal choice due to interplay effects. To satisfy both TT extensions and interplay, RG with a gate width as large as possible within safety limits is desirable.

Influence of repeated mastitis on the milk production and metabolic status in the subsequent lactation period of dairy cattle.

Recurrent mastitis poses a common challenge on dairy farms. While the impact of repeated mastitis within the same lactation has been investigated, the difference from one lactation to the next, particularly concerning the change of milk and blood metabolites, remains unclear. This study aimed to examine the difference in milk yield, milk composition, and metabolic status in the subsequent lactation between healthy and repeated mastitis in the previous lactation. The study population comprised 50 cows chosen from 400 cows, with 25 having no history of mastitis and 25 experiencing mastitis more than three times during the last lactation. Following dry-off and calving, all cows initiated a new lactation, during which no mastitis was diagnosed until the sample collection period. In the group exposed to repeated mastitis, a significant decrease in milk fat levels was observed in the subsequent lactation, while no change was observed in milk somatic cell count (SCC). Milk collected from cows that had experienced repeated mastitis in the previous lactation exhibited significant increases in the levels of free amino acids, namely valine, proline, and alanine. However, no difference in plasma levels of these amino acids was noted. These results indicate that individuals exposed to repeated mastitis have persistent milk quality changes even after dry-off. Biomarker analysis suggested that the milk valine and proline showed a moderate biomarker potential on Kappa coefficients to characterize cows that have experienced repeated mastitis. Furthermore, the results of biomarker combinations for valine and proline provided the highest specificity (100 %), positive likelihood ratio (infinity), and substantial biomarker potential on kappa coefficients (0.68). These findings significantly enhance our understanding of the pathobiology and etiology of recurrent mastitis and provide a biomarker to characterize cows that have experienced repeated mastitis in the past.

Histology of Bronchiolar Tumor Spread Through Air Spaces.

The clinical significance of lung tumor spread through air spaces (STAS) has been extensively studied, and is recognized as a unique pattern of invasion. Previous studies of STAS have focused primarily on STAS in alveolar spaces, whereas STAS in the bronchiolar spaces (bronchiolar STAS) has been described in only a few case reports only. Here, we examined 306 cases of primary lung adenocarcinoma and found that bronchiolar STAS was present in 18%. Bronchiolar STAS was associated with an inferior prognosis, more advanced stage, and higher histologic grade. No significant difference in clinicopathological factors or prognosis was observed between cases with bronchiolar STAS and those with alveolar STAS alone. Notably, bronchiolar STAS often occurred simultaneously with alveolar STAS and endobronchial spread of adenocarcinoma, particularly when bronchiolar STAS was present outside the main tumor. We also identified cases where bronchiolar STAS and endobronchial spread of adenocarcinoma occurred simultaneously in the same bronchi or bronchioles located outside the main tumor, as well as cases with bronchiolar STAS adjacent to intrapulmonary metastatic nodules. Our results highlight the significant role of bronchiolar STAS in the aerogenous spread of adenocarcinoma cells. Bronchiolar STAS can be regarded as a histologic variant of alveolar STAS. This study also supports the idea that STAS is not a tissue processing artifact, but a true biological process with clinical implications, offering histologic evidence of aerogenous spread in lung adenocarcinoma.