Asymptomatic mature intrapericardial teratoma in an adult: a case report of a rare condition.

BACKGROUND: Benign mature teratomas are the most common type of anterior mediastinal germ cell tumor. Mature intrapericardial teratomas are generally diagnosed during infancy because of symptoms of cardiac compression. In contrast, mature adult intrapericardial teratomas are extremely rare, accounting for less than 1% of mature intrapericardial teratomas. We describe herein a case of a mature intrapericardial teratoma in an asymptomatic adult. CASE PRESENTATION: A 52-year-old woman was found by computed tomography during a health checkup to have an anterior mediastinal mass. She was asymptomatic and hemodynamically stable with no evidence of heart failure. The preoperative provisional radiological diagnosis was a mature intrapericardial teratoma. A median sternotomy revealed an approximately 5-cm diameter protruding intrapericardial mass with a smooth surface. The mass was completely resected. Histopathological examination resulted in a diagnosis of a mature intrapericardial teratoma. The patient did well and has no evidence of recurrence 5 years after surgery. CONCLUSIONS: Mature intrapericardial teratomas in adults are extremely rare. Given the risks of malignant transformation, rupture, compression of the heart, and infection, excision is indicated to prevent development of serious manifestations.

[Educational Impact of Using Three-dimentional Models for Preoperative Simulation of Segmentectomy for Medical Students].

BACKGROUND: Lung segment anatomy is complex and difficult for medical students to comprehend, so education is a challenging issue. Three-dimensional (3D) models may be a more effective teaching tool for medical students. We evaluated the usefulness of 3D models in education for segmentectomy. METHODS: Sixty-six students who participated in clinical training for thoracic surgery from November 2020 to March 2022 were included in the study. Computed tomography (CT) images, 3D-CT images, and 3D models were used to investigate students' level of understanding for each lung segment. Levels of understanding were assessed using a questionnaire administered using the interview method. The results of the questionnaire were tabulated and analyzed using the Kruskal-Wallis test. RESULTS: The response rate was 100%. Comprehension scores for all questions were highest for 3D models, followed by 3D-CT and CT. These results suggest that use of a 3D entity model may have a high educational effect. CONCLUSION: Although it is unclear whether students' comprehension was directly related to their understanding of correct anatomy, our results suggest that 3D models may be an effective way for medical students to understand lung segmentectomy.

Impact of central nervous system metastasis after complete resection of lung adenocarcinomas harboring common EGFR mutation - A real-world database study in Japan: The CReGYT-01 EGFR study.

OBJECTIVES: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. CONCLUSION: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

Salivary metabolites as potential predictive biomarkers for lung surgery complications: a retrospective cross-sectional study.

PURPOSE: Saliva is often used as a tool for identifying systemic diseases because of the noninvasive nature of its collection. Moreover, salivary metabolites can be potential predictive factors for postoperative survival. We conducted the present study to establish whether salivary metabolites can function as predictive biomarkers for lung surgery complications. METHODS: Unstimulated salivary samples were collected from 412 patients before lung surgery. Salivary metabolites were analyzed comprehensively by capillary electrophoresis mass spectrometry. Clinical data with the discriminatory ability of biomarkers were assessed to predict lung surgery complications using multivariate logistic regression analysis. The primary endpoint was the risk factors for postoperative complications of Clavien-Dindo grade ≥ III. RESULTS: Postoperative complications of Clavien-Dindo grade ≥ III developed in 36 patients (8.7%). There was no postoperative 30-day mortality. Male sex (odds ratio [OR], 3.852; 95% confidence interval CI 1.455-10.199; p = 0.007) and salivary gamma-butyrobetaine (OR, 0.809; 95% CI 0.694-0.943; p = 0.007) were identified as significant risk factors for postoperative complications of Clavien-Dindo grade ≥ III. CONCLUSION: Salivary metabolites are potential noninvasive biomarkers for predicting postoperative complications of lung surgery.

Algorithm for spin symmetry operation search.

A spin space group provides a suitable way of fully exploiting the symmetry of a spin arrangement with a negligible spin-orbit coupling. There has been a growing interest in applying spin symmetry analysis with the spin space group in the field of magnetism. However, there is no established algorithm to search for spin symmetry operations of the spin space group. This paper presents an exhaustive algorithm for determining the spin symmetry operations of commensurate spin arrangements. The present algorithm searches for spin symmetry operations from the symmetry operations of a corresponding nonmagnetic crystal structure and determines their spin-rotation parts by solving a Procrustes problem. An implementation is distributed under a permissive free software license in spinspg Version 0.1.1, available at https://github.com/spglib/spinspg.

Synthesis of isomaltooligosaccharides using 4-O-α-d-isomaltooligosaccharylmaltooligosaccharide 1,4-α-isomaltooligosaccharohydrolase.

Isomaltooligosaccharides (IMOs), including isomaltose, are valuable oligosaccharides, and the development of methods to synthesize high-purity IMOs has long been underway. We recently discovered a novel enzyme, 4-O-α-d-isomaltooligosaccharylmaltooligosaccharide 1,4-α-isomaltooligosaccharohydrolase (IMM-4IH), that showed promise for improving the synthesis process. In this study, we establish methods for synthesizing isomaltose and IMOs consisting of a variety of degrees of polymerization from starch using IMM-4IH. With 5% substrate, by combining IMM-4IH with 1,4-α-glucan 6-α-glucosyltransferase from Bacillus globisporus N75, the yield of isomaltose was 63.0%; incorporating isoamylase and cyclomaltodextrin glucanotransferase increased the yield to 75.3%. On the other hand, by combining IMM-4IH with 1,4-α-glucan 6-α-glucosyltransferase from Paenibacillus sp. PP710, IMOs were synthesized. The inclusion of isoamylase and α-amylase led to the 136 mM IMOs, consisting of oligosaccharides from isomaltose to isomaltodecaose, from 10% starch. The development of these efficient methods will be an important contribution to the industrial production of IMOs.

Learning Curve for Thoracoscopic Individual Basilar Segmentectomy: 18-Year Experience.

BACKGROUND: Thoracoscopic anatomical individual basilar segmentectomy remains challenging owing to the deep intraparenchymal location of the hilar structures and anatomical variations. We analyzed and reported the experience and progress of thoracoscopic anatomical individual basilar segmentectomy at our university hospital. METHODS: We retrospectively examined the patients who underwent anatomical basilar segmentectomy at our institution from January 2004 to December 2021. We divided our analysis period into two parts: the first period (2004-2012) was the introductory period of video-assisted thoracoscopic surgery (VATS) segmentectomy, and the second period (2013-2021) was the maturity period of VATS segmentectomy. The learning curve of the leading surgeon in the second period was also evaluated based on the operative time and cumulative sum value of the operative time. RESULTS: Overall, 127 cases were evaluated, among whom 33 and 94 cases were assessed during the introductory and maturity periods of thoracoscopic segmentectomy, respectively. Age (P = 0.003) and Charlson comorbidity index (P = 0.002) were higher in the second period than in the first period. Use of a uniport (P = 0.006) was higher, and postoperative hospitalization duration (P = < 0.001) and operative time (P = 0.024) were shorter in the second period than in the first period. A learning curve obtained during the maturity period showed: The inflection point for the learning curve of thoracoscopic basilar segmentectomy was reached after 42 cases. CONCLUSIONS: We have demonstrated a single institution's progress and learning curve for difficult segmentectomies. This may be helpful to institutions considering performing this surgery.

Erratum: Dendritic spine formation and synapse maturation in transcription factor-induced human iPSC-derived neurons.

[This corrects the article DOI: 10.1016/j.isci.2023.106285.].

Synthesis, optical properties and crystal structure of (E,E)-1,3-(3,4:9,10-dibenzododeca-1,11-diene-5,7-diyne-1,12-di-yl)benzene.

The de-hydro-benzannulene (E,E)-1,3-(3,4:9,10-dibenzododeca-1,11-diene-5,7-diyne-1,12-di-yl)benzene, C26H16, was successfully synthesized via photocatalyst-assisted stereoselective reductive de-sulfonyl-ation of 1,3-bis-{1-phenyl-sulfonyl-2-[2-(tri-methyl-silylethyn-yl)phen-yl]ethen-yl}benzene, C44H42O4S2Si2, and subsequent desilylative cyclization of the resulting (E,E)-bis-silyl-protected dienyne, C32H34Si2. The structure of the de-hydro-benzannulene thus obtained was confirmed by single-crystal X-ray analysis; three benzene rings are connected to one another by a 1,3-butadiynylene and a pair of ethenylene arrays. Although the π-system expanded efficiently in the de-hydro-benzannulene, it was observed that the butadiynylene and ethenylene arrays were strained, showing smaller [171.3 (2)-172.6 (2) °] and larger bond angles [122.5 (2)-131.9 (2)°] than the conventional bond angles, respectively. In CHCl3, the de-hydro-benzannulene showed the longest absorption band at 377 nm. When irradiated by UV light, it emitted fluorescence at 468 nm (ΦF = 0.26) and 504 nm (ΦF = 0.24) in CHCl3 and in the powdered state, respectively.

Alkyne-tethered oligodeoxynucleotides that allow simultaneous detection of multiple DNA/RNA targets using Raman spectroscopy.

Detection of multiple DNA/RNA targets is essential for understanding cellular function. Herein, we propose a general method for the simultaneous detection of plural nucleic acids based on surface-enhanced Raman scattering (SERS) using gold nanoparticles bearing functional oligodeoxynucleotides (ODNs) on their surface. Modified ODNs bearing an acetylene tag hybridized with their complementary ODNs on the surface of the gold nanoparticles, inducing a strong SERS signal of the acetylene tag. The addition of the target nucleic acid to the system resulted in a spontaneous displacement of the strand on the particle and dissociation of the alkyne-tagged ODN from the particle, resulting in a dramatic decrease in signal intensity. By using an alkyne tag for each of the multiple target nucleic acids, each target could be detected simultaneously. In addition, we successfully detected cellular microRNA. Different targets showed changes with different wavenumbers in the Raman spectra, allowing for the detection of multiple nucleic acids.

[Minimally Invasive Surgery for Mediastinal Diseases in Our Institute:Innovations and Surgical Practice].

Since the early 1990s, minimally invasive surgery has been introduced in many surgical fields. The progress of technology and increased interest in minimally invasive surgery has led to innovation from surgery with a large incision to complete thoracoscopic surgery in many facilities. We started thoracoscopic mediastinal surgery in 1997 and robot-assisted mediastinal surgery in 2021. Considering the approach for anterior mediastinal tumor resection, it is necessary to fully understand tumor size, tumor location, and the existence of the tumor invasion to other organs. Especially in the case of tumors located on the cranial side above the innominate vein or thymectomy with dissection of the superior pole of the thymus, ensuring surgical field visibility is essential. In our institute, from the point of cosmetics, surgical field visibility is ensured using carbon dioxide insufflation and a sternum-lifting method. Although the number of cases is limited, we report our ingenuity and actual implementation of the techniques.

High body temperature increases gut microbiota-dependent host resistance to influenza A virus and SARS-CoV-2 infection.

Fever is a common symptom of influenza and coronavirus disease 2019 (COVID-19), yet its physiological role in host resistance to viral infection remains less clear. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C increases host resistance to viral pathogens including influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High heat-exposed mice increase basal body temperature over 38 °C to enable more bile acids production in a gut microbiota-dependent manner. The gut microbiota-derived deoxycholic acid (DCA) and its plasma membrane-bound receptor Takeda G-protein-coupled receptor 5 (TGR5) signaling increase host resistance to influenza virus infection by suppressing virus replication and neutrophil-dependent tissue damage. Furthermore, the DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamsters from lethal SARS-CoV-2 infection. Moreover, we demonstrate that certain bile acids are reduced in the plasma of COVID-19 patients who develop moderate I/II disease compared with the minor severity of illness group. These findings implicate a mechanism by which virus-induced high fever increases host resistance to influenza virus and SARS-CoV-2 in a gut microbiota-dependent manner.

Revaluation of a selected segmental insufflation technique in total thoracoscopic lung segmentectomy.

We report selected insufflation technique using direct bronchial insufflation to visualize the intersegmental plane during total thoracoscopic segmentectomy. Following the transection of the bronchus using a stapler, a small incision was created in the dissected target bronchus, and direct air insufflation was performed at the small incision site. The target segment was inflated, while the preserved segments appeared to collapse, and a demarcating line was visualized between the inflated and deflated lung parenchyma. This technique quickly identifies the anatomic intersegmental plane without warranting special equipment such as jet ventilation or indocyanine green (ICG). Furthermore, this method saves time in creating inflation-deflation lines.

Dendritic spine formation and synapse maturation in transcription factor-induced human iPSC-derived neurons.

Synaptic maturation is reportedly limited in human induced pluripotent stem cell (iPSC)-derived neurons. Notably, their ability to reach postnatal-like stages and form dendritic spines has been difficult to demonstrate unless using long-term cultured organoids. Recent transcription factor (TF)-based induction methods allow the accelerated generation of differentiated neurons, which offers an unprecedented opportunity to address further progression into late developmental stages. Herein, we report on a comprehensive time-course study of TF-induced iPSC neurons cultured in vitro through an intrinsic maturation program following neurogenesis. Moreover, we determined the transcriptional and morphological sequences of key developmental events associated with spinogenesis, including the conversion of drebrin to its brain-specific isoform A and the N-methyl-D-aspartate (NMDA) receptor subunit switch. TF-induced iPSC neurons successfully acquired structural and functional synaptic maturity, which will critically expand their utility in modeling higher brain functions and disorders.

The preoperative assessment of thoracic wall adhesions using four-dimensional computed tomography.

OBJECTIVE: Pleural adhesions are challenging during lung cancer surgery and may be associated with a long surgery time and excessive blood loss due to pleural adhesiolysis. We used preoperative four-dimensional computed tomography to quantitatively assess parietal pleural adhesions and determine its diagnostic accuracy. METHODS: A total of 216 patients with lung cancer underwent four-dimensional computed tomography during the study period. Pleural adhesions were subsequently confirmed by surgery in 85 of these patients, whereas 126 patients had no adhesions. The movements of the tumor or target vessels (α) was tracked. Receiver-operating characteristic curve analysis was used to identify the relationship between adhesions and (α). RESULTS: The movement of (α) was smaller in patients with adhesions than in those without adhesions. The greater the adhesion, the shorter the movement distance (p < 0.001). Receiver-operating characteristic curve analysis demonstrated an area under the curve for the moving (α) point at 0.71 (95% confidence interval: 0.62-0.80) in the upper lung field and at 0.75 (95% confidence interval: 0.64-0.85) in the lower field. To identify adhesions, a cut off of 11.3 mm (sensitivity = 43.6%, specificity = 93.2%) in the upper lung field and a cut off of 41.2 mm (sensitivity = 71.4%, specificity = 66.0%) in the lower lung field were established. CONCLUSIONS: Four-dimensional computed tomography is a novel and helpful modality for predicting the presence of parietal pleural adhesions. To obtain robust evidence, further accumulation of cases and re-examination of the analysis methods are needed.

Residual middle lobectomy after right upper or lower lobectomy: indications and outcome.

OBJECTIVES: Residual middle lobectomy after upper lobectomy and lower lobectomy differs in their indications and perioperative outcomes. Therefore, we aimed to evaluate the indications and perioperative outcomes of residual middle lobectomy after upper and lower lobectomy. METHODS: The data of 14 patients who underwent residual middle lobectomy after upper or lower lobectomy between January 1997 and December 2021 were extracted and analyzed. RESULTS: Overall, six patients underwent residual middle lobectomy after upper lobectomy. The indication was second primary lung cancer in five patients and local recurrence in the hilar lymph node between the middle and lower lobar bronchi in one patient. However, one patient was treated with the R2 operation. The remaining eight patients underwent residual middle lobectomy after lower lobectomy. The indication was second primary lung cancer and bronchopleural fistula or stenosis in two and six patients, respectively. No postoperative 90-day mortality was observed. CONCLUSIONS: Residual middle lobectomy for second lung cancer after upper lobectomy is difficult because of severe hilar adhesions. Simultaneous resection of hilar structures or pulmonary artery and parenchyma might be an option. Residual middle lobectomy could be a treatment option for bronchopleural fistula or stenosis after lower lobectomy.

Cloning and sequence analysis of 4-O-α-d-isomaltooligosaccharylmaltooligosaccharide 1,4-α-isomaltooligosaccharohydrolase from Sarocladium kiliense U4520.

A novel enzyme, 4-O-α-d-isomaltooligosaccharylmaltooligosaccharide 1,4-α-isomaltooligosaccharohydrolase (IMM-4IH), was previously discovered from Sarocladium kiliense U4520. In order to identify the factors underlying the unique substrate specificity of IMM-4IH, we endeavored to determine the amino acid sequence of the enzyme. By comparing the partial amino acid sequence of the enzyme to whole genome sequencing data of S. kiliense U4520, the IMM-4IH gene was estimated. The putative gene was expressed in Pichia pastoris, and its activity and properties were found to be consistent with those of the native enzyme. Comparing the amino acid sequence of IMM-4IH with those in the CAZy database led to classification in the glycoside hydrolase family 49 (GH49). Several amino acids important for catalysis (Asp406, Asp425, and Asp426) and substrate recognition at subsites + 1 and -3 were estimated by multiple sequence alignment analysis. These results provide important information for characterizing IMM-4IH and other GH49 enzymes.

Thoracoscopic Lateral Basal Segmentectomy Based on Dissection Along the Intersegmental Veins.

In the conventional method of lateral basal (S9) segmentectomy, the intersegmental plane is first divided between the superior segment and the anterior segment, then the S9 segment is removed from the other basilar segments. We show here our modified method of thoracoscopic S9 segmentectomy based on dissection along the intersegmental veins. Our technique is unique in that we do not divide the intersegmental plane between the superior segment and the anterior segment. The merits are that it avoids additional parenchymal splitting from the superior segment and that it may be used when an incomplete interlobar fissure is present.