Cellular-resolution gene expression profiling in the neonatal marmoset brain reveals dynamic species- and region-specific differences.

Precise spatiotemporal control of gene expression in the developing brain is critical for neural circuit formation, and comprehensive expression mapping in the developing primate brain is crucial to understand brain function in health and disease. Here, we developed an unbiased, automated, large-scale, cellular-resolution in situ hybridization (ISH)-based gene expression profiling system (GePS) and companion analysis to reveal gene expression patterns in the neonatal New World marmoset cortex, thalamus, and striatum that are distinct from those in mice. Gene-ontology analysis of marmoset-specific genes revealed associations with catalytic activity in the visual cortex and neuropsychiatric disorders in the thalamus. Cortically expressed genes with clear area boundaries were used in a three-dimensional cortical surface mapping algorithm to delineate higher-order cortical areas not evident in two-dimensional ISH data. GePS provides a powerful platform to elucidate the molecular mechanisms underlying primate neurobiology and developmental psychiatric and neurological disorders.

Identification of compounds that preferentially suppress the growth of T-cell acute lymphoblastic leukemia-derived cells.

T-cell acute lymphoblastic leukemia (T-ALL) is one of the most frequently occurring cancers in children and is associated with a poor prognosis. Here, we performed large-scale screening of natural compound libraries to identify potential drugs against T-ALL. We identified three low-molecular-weight compounds (auxarconjugatin-B, rumbrin, and lavendamycin) that inhibited the proliferation of the T-ALL cell line CCRF-CEM, but not that of the B lymphoma cell line Raji in a low concentration range. Among them, auxarconjugatin-B and rumbrin commonly contained a polyenyl 3-chloropyrrol in their chemical structure, therefore we chose auxarconjugatin-B for further analyses. Auxarconjugatin-B suppressed the in vitro growth of five human T-ALL cell lines and two T-ALL patient-derived cells, but not that of adult T-cell leukemia patient-derived cells. Cultured normal T cells were several-fold resistant to auxarconjugatin-B. Auxarconjugatin-B and its synthetic analogue Ra#37 depolarized the mitochondrial membrane potential of CCRF-CEM cells within 3 h of treatment. These compounds are promising seeds for developing novel anti-T-ALL drugs.

Dual Image Navigation to Secure Surgical Margins in Thoracoscopic Segmentectomy.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) segmentectomy is being increasingly used for the management of non-small cell lung cancer. For non-palpable lesions, surgeons frequently find difficulty in ensuring a sufficient surgical resection margin. OBJECTIVE: The purpose of this study was to evaluate the role of intraoperative dual image navigation in combination with the infrared thoracoscopy with intravenous injection of indocyanine green (IRT-ICG) method and intraoperative computed tomography (CT) in detecting oncological margins. METHODS: This study involved 34 consecutive patients who underwent both IRT-ICG and intraoperative CT-assisted thoracoscopic segmentectomy between October 2017 and July 2021. The intersegmental line on the visceral pleura was visualized using the IRT-ICG method. The intersegmental line was marked by clipping, and an intraoperative CT scan was performed under bilateral lung ventilation. Intraoperative CT or three-dimensional CT reconstruction images were used by surgeons to confirm the correct anatomic segmental border and to secure a sufficient resection margin. RESULTS: A well-defined intersegmental line was observed in 91.2% of patients. In eight cases, the surgeon needed to make some modifications to the resection line to secure a sufficient surgical margin. The mean surgical margin assessed on gross examination by the pathologist was 23.4 ± 9.0 mm. Complete resection was achieved in all patients using this approach. CONCLUSIONS: Intraoperative dual image navigation combined with the IRT-ICG method and intraoperative CT scan enables surgeons to perform definitive VATS segmentectomy for non-palpable lesions.

Synthesis and anti-tumor activities in human leukemia-derived cells of polyenylpyrroles with a methyl group at the conjugated polyene terminus.

To develop novel drugs for treating T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) which are highly malignant hematological tumors, a series of analogs having a polyenylpyrrole structure of natural compounds (rumbrin and auxarconjugatin B) were synthesized and investigated their structure-activity relationships (SAR) of in vitro anti-T-ALL and anti-AML activities. We obtained three findings: (1) introduction of a methyl group at the conjugated polyene terminus enhanced anti-T-ALL activity, (2) analogs with a 3-chloropyrrole moiety had even higher selectivity for T-ALL cells, and (3) some analogs were effective against AML-derived cells. Among the studied compounds, 3-chloro-2-(8-ethoxycarbonylnona-1,3,5,7-tetraenyl) pyrrole 4e was the most promising candidate of T-ALL- and AML-treating drug. This study provides useful structural information for designing novel drugs treating T-ALL and AML.

Potentialities of CdZnTe Quasi-Hemispherical Detectors for Hard X-ray Spectroscopy of Kaonic Atoms at the DAΦNE Collider.

Kaonic atom X-ray spectroscopy is a consolidated technique for investigations on the physics of strong kaon-nucleus/nucleon interaction. Several experiments have been conducted regarding the measurement of soft X-ray emission (<20 keV) from light kaonic atoms (hydrogen, deuterium, and helium). Currently, there have been new research activities within the framework of the SIDDHARTA-2 experiment and EXCALIBUR proposal focusing on performing precise and accurate measurements of hard X-rays (>20 keV) from intermediate kaonic atoms (carbon, aluminum, and sulfur). In this context, we investigated cadmium-zinc-telluride (CdZnTe or CZT) detectors, which have recently demonstrated high-resolution capabilities for hard X-ray and gamma-ray detection. A demonstrator prototype based on a new cadmium-zinc-telluride quasi-hemispherical detector and custom digital pulse processing electronics was developed. The detector covered a detection area of 1 cm2 with a single readout channel and interesting room-temperature performance with energy resolution of 4.4% (2.6 keV), 3% (3.7 keV), and 1.4% (9.3 keV) FWHM at 59.5, 122.1, and 662 keV, respectively. The results from X-ray measurements at the DAΦNE collider at the INFN National Laboratories of Frascati (Italy) are also presented with particular attention to the effects and rejection of electromagnetic and hadronic background.

Model-based estimation of QT intervals of mouse fetal electrocardiogram.

BACKGROUND: Abnormal prolongation in the QT interval or long QT syndrome (LQTS) is associated with several cardiac complications such as sudden infant death syndrome (SIDS). LQTS is believed to be linked to genetic mutations which can be understood by using animal models, such as mice models. Nevertheless, the research related to fetal QT interval in mice is still limited because of challenges associated with T wave measurements in fetal electrocardiogram (fECG). Reliable measurement of T waves is essential for estimating their end timings for QT interval assessment. RESULTS: A mathematical model was used to estimate QT intervals. Estimated QT intervals were validated with Q-aortic closure (Q-Ac) intervals of Doppler ultrasound (DUS) and comparison between both showed good agreement with a correlation coefficient higher than 0.88 (r > 0.88, P < 0.05). CONCLUSION: Model-based estimation of QT intervals can help in better understanding of QT intervals in fetal mice.

Synthesis of polyenylpyrrole derivatives with selective growth inhibitory activity against T-cell acute lymphoblastic leukemia cells.

T-cell acute lymphoblastic leukemia (T-ALL) is a hardly curable disease with a high relapse rate. 20 analogs were synthesized based on the structures of two kinds of fungi-derived polyenylpyrrole products (rumbrin (1) and auxarconjugatin-B (2)) to suppress the growth of T-ALL-derived cell line CCRF-CEM and tested for growth-inhibiting activity. The octatetraenylpyrrole analog gave an IC50 of 0.27 µM in CCRF-CEM cells, while it did not affect Burkitt lymphoma-derived cell line Raji and the cervical cancer cell line HeLa, or the oral cancer cell line HSC-3 (IC50 > 10 µM). This compound will be a promising compound for developing T-ALL-specific drugs.

Development of Three-Dimensional Cell Culture Scaffolds Using Laminin Peptide-Conjugated Agarose Microgels.

Three-dimensional (3D) cell scaffolds are essential for tissue engineering. So far, various polymer hydrogels have been utilized to design 3D scaffolds as a biomaterial. In this study, we focused on a biocompatible polysaccharide, agarose, as a potential biomaterial candidate. We have previously established a laminin-derived cell adhesive peptide library, and these peptides are useful for incorporating cell adhesiveness into inert materials. We synthesized aldehyde-functionalized agarose (CHO-agarose) by (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) oxidation of agarose and developed peptide-agarose scaffolds using two laminin peptides, CGG-A99 (CGGAGTFALRGDNPQG, binds to αvß3 integrin) and CGG-AG73 (CGGRKRLQVQLSIRT, binds to syndecan). The peptides were effectively loaded onto the CHO-agarose gels via thiazolidine formation without coupling reagents. Two-dimensional (2D) cell culture assay using human dermal fibroblasts (HDFs) showed that the peptide-agarose gels have potent cell adhesion activity and promoted cell proliferation. Furthermore, we developed a simple preparation method of 3D cell culture scaffolds using peptide-agarose microgels. HDFs cultured in a 3D environment of the A99-agarose microgel scaffold exhibited cell spreading morphology and proliferated significantly. These results suggest that 3D cell culture systems using peptide-agarose microgel scaffolds are promising as a biomaterial for tissue engineering.

[Thoracoscopic Diaphragmatic Stitching for the Catamenial Pneumothorax].

A 46-year-old woman experienced an initial episode of right-sided spontaneous pneumothorax at the time of menstruation. The findings of thoracoscopic examination suggested catamenial pneumothorax. Thoracoscopic surgery revealed multiple blueberry spots on the diaphragm. Considering the patient to be premenopausal within several years and expecting postoperative hormonal therapy, we stitched all lesions without resection for detailed histopathological diagnosis. The patient is well 5 months postoperatively.

[Surgical Repair for the Ventricular Septal Perforation Following Blunt Chest Trauma;Report of a Case].

Ventricular septal perforation(VSP) after blunt chest trauma is rare. As the clinical symptoms and timing of presentation are varied, appropriate diagnosis can be difficult or delayed. An 86-year-old man presented with a traumatic VSP following a forestry injury. He showed a normal cardiac structure at the time of injury, but echocardiography after 9 days revealed VSP. He was treated successfully with surgical closure of the VSP.

Property of Human Bone Marrow Stromal Cells Derived From Bone Fragments Removed in Sagittal Split Ramus Osteotomy.

Bone tissue engineering is in the process of making the shift from bench to bed. Organ as a cell source is important for tissue engineering. The appropriate cells should be harvested without invasiveness and ethical problems. The authors focused on mandibular cortex bone fragments removed in sagittal split ramus osteotomy as a cell source for bone tissue engineering. These bone fragments were discarded after surgery until now. Bone marrow stromal cells (BMSCs) were harvested from inside of bone fragments, which is an endosteal region. Endosteal region is known to be a hematopoietic stem cell niche and harbors osteoblasts, preosteoblasts, and mesenchymal stem cells (MSCs). Bone marrow stromal cells could be cultured easily, and grew rapidly in vitro under ordinary serum-supplemented culture condition. The expression pattern of surface markers of BMSCs was the same as that of MSCs. Bone marrow stromal cells could differentiated into multiple mesenchymal lineages (osteoblasts, adipocytes, chondrocytes, and smooth muscle cells). These results indicated the existence of MSCs in BMSCs. The osteoblastic characters of BMSCs were examined more closely. Bone marrow stromal cells showed a high alkaline phosphatase activity, and expressed osteoblastic markers (PTHr, bone sialoprotein, Type I collagen, Rnut-related transcription factor 2, and osteocalcin). In transplantation experiments, BMSCs generated ectopic bone tissues on the border of hydroxyapatite scaffold without osteogenic differentiation-inducing agents such as dexamethasone (Dex) or bone morphogenetic protein. The results of this study suggest that mandibular cortex bone fragments removed in sagittal split ramus osteotomy are a good cell source for bone tissue engineering.

[Tension Hemothorax Associated with Spontaneous Rupture of the Thoracic Aorta;Report of a Case].

A 94-year-old woman was admitted to our hospital with sudden onset of chest pain without any episode of trauma. Computed tomography(CT) revealed left massive pleural effusion and extravasation of contrast medium from the side chest wall to the back. Neither aortic aneurysm nor dissection was evident. During the investigation, the patient went into hypovolemic shock. Hemothorax due to bleeding from an intercostal artery was diagnosed, and emergency surgery was performed. A 1-mm hole was detected in the descending aorta, and closed by a single suture. The final diagnosis was spontaneous rupture of the thoracic aorta. Three-dimensional CT (3D-CT), reconstructed postoperatively, revealed extravasation of the contrast medium from the descending aorta. The postoperative course was satisfactory, and the patient was discharged on the 20th postoperative day. 3D-CT may be useful for identifying the source of bleeding in such cases.

Tracheal repair with sternocleidomastoid flap in mediastinoscopic surgery for esophageal cancer.

Tracheal injury during mediastinoscopic esophagectomy is a life-threatening complication that is challenging to manage. However, no precise treatment has been defined. An 80-year-old male patient with upper esophageal cancer underwent a mediastinoscopic esophagectomy and gastric tube reconstruction through the posterior mediastinal route. When the esophagus was separated from the trachea using a bipolar vessel sealing system, the left side of the membranous trachea incurred a 3-cm defect 7 cm below the sternal notch. We successfully repaired the tracheal injury not by directly suturing the defect but by reinforcing it with a pedicle sternocleidomastoid flap. The gastric tube was placed over the tracheal repair for esophageal reconstruction via a posterior mediastinal route. As a result, the patient recovered well and was discharged. A sternocleidomastoid flap might be another surgical option for reinforcement flaps in tracheal injuries.

Recurrence-free survival curve for pulmonary metastasectomy in colorectal cancer plateaus at 3 years.

Pulmonary metastasectomy in colorectal cancer (CRC) has encouraging results; however, specific criteria for lung resection and the timing of resection remain undetermined. Therefore, in this study, we aimed to examine the long-term prognosis and 10-year survival rates and analyze poor prognostic factors in patients who underwent resection of pulmonary metastases from CRC. This retrospective, single-institution study included 156 patients with controlled primary CRC and metastases confined to the lungs or liver who underwent pulmonary metastasectomy between 2005 and 2022. Statistical analyses were conducted using the X2 and two-tailed Student's t test to compare variables. The receiver operating characteristic (ROC) curve was used to determine the appropriate cut-off point for tumor size as a predictive factor of survival. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and non-parametric group comparisons were performed using log-rank tests. The 5- and 10-year OS rates were 67% and 59%, respectively. Further, there was no recurrence 38 months post-surgery, and the RFS curve plateaued. Moreover, by 88 months post-surgery, no deaths occurred, and the OS curve plateaued. Multivariate analysis revealed that a pulmonary metastatic tumor >14 mm and disease-free interval <2 years indicated poor prognosis. The RFS curve for pulmonary metastasectomy may plateau approximately 3 years after surgery. Pulmonary metastasectomy can achieve long-term survival in selected patients with CRC. Furthermore, surgical resection of recurrence after pulmonary metastasectomy may lead to better results. Thus, tumor size and disease-free interval may be independent prognostic factors.

Siglec10 Expression on Tumor-associated Macrophages Is an Independent Prognostic Factor in Stage I Lung Adenocarcinoma.

BACKGROUND/AIM: Prognostic indicators for postoperative lung adenocarcinoma are elusive. The interaction between CD24 on tumor cells and sialic-acid-binding Ig-like lectin 10 (Siglec10) on tumor-associated macrophages (TAMs) is implicated in immune evasion in distinct tumors. However, the therapeutic significance of phagocytic checkpoints in lung adenocarcinoma remains unknown. We aimed to investigate the clinical relevance and prognostic significance of phagocytosis checkpoints mediated by Siglec10 in TAMs of patients with lung adenocarcinoma who underwent curative resection. PATIENTS AND METHODS: In this single-center retrospective study, we analyzed the data of 423 patients with stage I lung adenocarcinoma resected between 1999 and 2016. Tissue microarrays were constructed, and CD24, CD68, and Siglec10 immunohistochemistry was performed. Additionally, we assessed the clinical significance and prognostic associations of these markers. RESULTS: CD24 expression was higher in the Siglec10-high expression group than that in the -low expression group. Multivariate analysis showed that combined high Siglec10 and CD24 expression was an independent predictor of recurrence-free probability. The combined high Siglec10 and CD68 expression was a significant independent predictor of overall survival. Univariate analysis demonstrated that the 5-year probability of post-recurrence survival of patients with combined high Siglec10 and CD68 expression was lower than that of the other patients. CONCLUSION: High TAM Siglec10 expression and tumor CD24 expression are correlated, and the high Siglec10+CD24 combination is a major risk factor for recurrence. CD68+Siglec10 TAMs are important prognostic factors. Siglec10 expression on TAMs is essential for tumor microenvironment immunoregulation and offers a promising new immunotherapeutic approach for lung adenocarcinoma.

[Mucosa-associated lymphoid tissue (MALT) lymphoma of the lung treated by surgery and rituximab; report of a case].

We report a case of mucosa-associated lymphoid tissue (MALT) lymphoma of the lung treated by surgery and rituximab. A 47-year-old man was referred to our hospital because of the lesion in the right middle lobe, which had enlarged gradually. Chest computed tomography(CT) scanning showed an infiltrative shadow of the right middle lobe. He underwent right middle lobectomy for the MALT lymphoma whose diagnosis and treatment. The tumor was pathologically diagnosed as CD20 immunostaining was positive and the adjuvant treatment by rituximab was performed.

[Two cases of recurrent invasive mucinous adenocarcinoma of the lung showing marked responses to platinum-based chemotherapyregimens with pemetrexed and bevacizumab].

Here, we report 2 cases of recurrent invasive mucinous adenocarcinoma of the lung after surgery, which showed marked responses to platinum-based regimens with pemetrexed(PEM)and bevacizumab(BEV). The first patient was diagnosed with stage I B(p-T2N0M0)invasive mucinous adenocarcinoma, and new nodules were detected on computed tomography (CT)after 24 months of adjuvant chemotherapy with uracil/tegafur(UFT). Therefore, the patient was administered carboplatin(CBDCA; AUC 5.0), PEM(500mg/m2), and BEV(15mg/kg)for 6 courses followed by BEV(15mg/kg)for 3 courses, resulting in a complete response. The second patient was diagnosed with stage IV(p-T3N0M1)invasive mucinous adenocarcinoma, and metastases appeared after the surgery. The patient was treated with S-1 for 18 weeks, but the tumor recurred 18weeks after surgery. Therefore, the patient was administered 4 courses of cisplatin(CDDP 60mg/m2), PEM(500mg/m2), and BEV(15mg/kg)followed by 5 courses of PEM(15mg/kg)as maintenance therapy. This resulted in a good response. The first patient had grade 3 toxicities at the sixth course of combined CBDCA-PEM-BEV therapy, while the second patient did not have any adverse events throughout chemotherapy. These 2 cases showed that platinum-based regimens with PEM and BEV may be a good choice for patients with invasive mucinous adenocarcinoma of the lung.

CD44v6 downregulation as a prognostic factor for distant recurrence in resected stage I lung adenocarcinomas.

CD44 and CD44 variant isoforms have been reported as contributing factors to cancer progression. In this study, we aimed to assess whether CD44 and its variant isoforms were correlated with the prognostic factors for distant metastasis in stage I lung adenocarcinomas using tissue microarray and immunohistochemistry. In this single-center retrospective study, we analyzed the data of 490 patients with stage I lung adenocarcinoma resected between 1999 and 2016. We constructed tissue microarrays and performed immunohistochemistry for CD44s, CD44v6, and CD44v9. The risk of disease recurrence and its associations with clinicopathological risk factors were assessed. CD44v6 expression was significantly associated with recurrence. Patients with CD44v6-negative tumors had a significantly increased risk of developing distant recurrence than patients with CD44v6-positive tumors (5-year cumulative incidence of recurrence (CIR), 10.7% vs. 4.6%; P = 0.009). However, CD44v6-negative tumors were not associated with an increased risk of locoregional recurrence compared to CD44v6-positive tumors (5-year CIR, 6.0% vs. 4.0%; P = 0.39). The overall survival (OS) of patients with CD44v6-negative tumors was significantly lower than that of patients with CD44v6-positive tumors (5-year OS: 87% vs. 94%, P = 0.016). CD44v6-negative tumors were also associated with invasive tumor size and lymphovascular invasion. Even in stage I disease, tumors with negative-CD44v6 expression had more distant recurrences than those with positive-CD44v6 expression and were associated with poor prognosis in resected stage I lung adenocarcinomas. Thus, CD44v6 downregulation may be a prognostic factor for distant metastasis in stage I lung adenocarcinomas.

Investigating the association of maternal heart rate variability with fetal birth weight.

Maternal heart rate (HR) was reported to affect birth weight and birth outcomes. Low birth weight constitutes a major health problem, and it is estimated that around 15% to 20% of births worldwide are low weight. In our previous study, we discussed the presence of similarities between maternal and fetal HRs, therefore, here, we propose to develop a parameter based on maternal and fetal HR variability (HRV) to divide data into two patterns to investigate the association of fetal birth weight with maternal HR and HRV. The parameter was derived from non-invasive records of maternal and fetal electrocardiograms (ECGs) that were collected from 78 subjects (age: 22 - 44 years old, gestational age (GA): 19 - 40 weeks). The HRV parameter was calculated by first evaluating the standard deviation (SD) of the number of R peaks occurring per 2 seconds (snRpp2s). Then, the difference between maternal and fetal snRpp2s (dmf) was calculated. The correlation between our derived parameter [dmf] with GA revealed a significant correlation that suggested the dmf's association with fetal development. The association analysis results between birthweight with maternal HR and HRV per pattern showed that significant negative correlations exist between them in one pattern. Still, the same correlations were not observed in the other pattern. This study's findings emphasise maternal health's role in fetal development assessment. In addition, this study highlights the importance of developing novel factors for properly assessing fetal development and birth outcomes.