Better survival with lobectomy versus. sublobar resection in patients with hypermetabolic c-stage IA lung cancer on positron emission tomography/computed tomography.

OBJECTIVES: The clinical trial showed that sublobar resection was not inferior to lobectomy in terms of disease-free survival in patients with peripherally located non-small cell lung cancer ≤ 2 cm. However, it is not clear whether sublobar resection is indicated for all types of c-stage IA lung cancer. The purpose of this study was to clarify whether sublobar resection is indicated for c-stage IA hypermetabolic lung cancer. METHODS: Patients with c-stage IA lung cancer who underwent F-18 fluorodeoxyglucose positron emission tomography/computed tomography and lobectomy or sublobar resection were assessed. Of these, patients had a maximum standardized uptake value ≥ 3.0 on positron emission tomography/computed tomography were evaluated. We compared survival rates after lobectomy versus sublobar resection. Propensity score matching was performed to balance patient characteristics between groups. RESULTS: Between April 2004 and March 2023, 723 patients underwent lobectomy or sublobar resection and had a maximum standardized uptake value ≥ 3.0 on positron emission tomography/computed tomography. Lobectomy and sublobar resection were performed in 532 (73.6%) and 191 (26.4%) patients, respectively. Both the 5-year overall and disease-free survival rates were worse after sublobar resection compared with lobectomy (62.3% vs 79.9% and 53.9% vs 70.3%, respectively). After propensity score matching, the 5-year overall and disease-free survival rates remained worse after sublobar resection compared with lobectomy (60.7% vs 75.2% and 51.6% vs 67.7%, respectively). CONCLUSIONS: Patients with c-stage IA hypermetabolic lung cancer with standardized uptake value ≥ 3.0 on positron emission tomography/computed tomography had a worse prognosis after sublobar resection than after lobectomy.

Quantitative evaluation of striatal uptake ratios using an adaptive template registration method for 123I-ioflupane dopamine transporter SPECT.

INTRODUCTION: 123I-FP-CIT (123I-Ioflupane) SPECT shows strong accumulation in the striatum, but morphological standardization is challenging due to low accumulation outside the striatum, particularly in subjects with marked striatal decline. In this study, morphological standardization without MRI was achieved using the adaptive template registration (ATR) method to create a subject-specific optimized template with weighted images of normal-type and egg-shape-type templates. The accuracy of a quantitative method for calculating the ratio with nonspecific accumulation in the occipital lobe was evaluated by placing voxels-of-interest (VOI) on standardized images, particularly targeting the striatum. METHODS: The average images of eight subjects, demonstrating normal-type and egg-shape-type tracer accumulation in 123I-Ioflupane SPECT, were utilized as normal and disease templates, respectively. The study included 300 subjects that underwent both 123I-Ioflupane SPECT and MRI for the diagnosis of suspected Parkinson's disease or for exclusion diagnosis. Morphological standardization of SPECT images using structural MRI (MRI-based method) was considered the standard of truth (SOT). Three morphological standardizations without MRI were conducted. The first involved conventional morphological standardization using a normal template (fixed template method), the second employed the ATR method, with a weighted template, and the third used the split-ATR method, processing the left and right striatum separately to address asymmetrical accumulation. VOIs were set on the striatum, caudate, putamen as regions of specific accumulation, and on the occipital lobe as a reference region for nonspecific accumulation. RESULTS: Results showed significant and robust linearity in the striatal accumulation ratios for all templates when compared with the occipital lobe accumulation ratio when using the MRI-based method. Comparing intra-class correlations for different linearities, the ATR method and split-ATR method demonstrated higher linearity in the striatum, caudate, and putamen. The split-ATR method showed similar improvements, although more linearity than some of the ATR methods; the effectiveness of the Split-ATR method may vary by image quality, and further validation of its effectiveness in diverse asymmetric accumulation cases seemed warranted. CONCLUSION: The use of optimized templates, such as the ATR and split-ATR methods, improved reproducibility in fully automated processing and demonstrated superior linearity compared to that of MRI-based method, in the ratio to the occipital lobe. The ATR method, which enables morphological standardization when using SPECT images only, proved highly reproducible for clinical quantitative analysis of striatal accumulation, facilitating its clinical use.

Comparison of segmentectomy and wedge resection for cT1cN0M0 non-small cell lung cancer.

OBJECTIVE: Sublobar resection is considered a standard surgical procedure for early non-small cell lung cancer, although the survival of patients undergoing sublobar resection for clinical T1cN0M0 non-small cell lung cancer remains unclear. This study aimed to compare survival between segmentectomy and wedge resection for clinical T1cN0M0 non-small cell lung cancer. METHODS: This retrospective study included patients who had undergone curative surgery for cT1cN0M0 stage IA3 non-small cell lung cancer. The overall and recurrence-free survival rates of 91 patients who underwent segmentectomy or wedge resection were compared. RESULTS: Thirty-nine (42.9%) and 52 patients (57.1%) were included in the segmentectomy and wedge resection groups, respectively. The median length of follow-up was 6.0 years (95% confidence interval 4.2 - - years) (Kaplan-Meier estimate). The 5 year overall survival rates were not significantly different between the segmentectomy and wedge resection groups (67.7% vs 52.0%, P = 0.132). The 5 year recurrence-free survival rate was worse in the wedge resection group than in the segmentectomy group (66.6% vs 46.9%, P = 0.047). In univariable analysis, spread through air spaces (hazard ratio, 5.889; 95% confidence interval, 2.357-14.715; P < 0.001) was an important prognostic factor for recurrence-free survival in the wedge resection group. CONCLUSIONS: The overall survival of patients who underwent segmentectomy for clinical T1cN0M0 non-small cell lung cancer was not significantly different from that of patients who underwent wedge resection. However, patients with cT1cN0M0 non-small cell lung cancer who underwent wedge resection tended to have a worse recurrence-free survival prognosis than those who underwent segmentectomy.

Magnetic parity violation and parity-time-reversal-symmetric magnets.

Parity-time-reversal symmetry (PTsymmetry), a symmetry for the combined operations of space inversion (P) and time reversal (T), is a fundamental concept of physics and characterizes the functionality of materials as well asPandTsymmetries. In particular, thePT-symmetric systems can be found in the centrosymmetric crystals undergoing the parity-violating magnetic order which we call the odd-parity magnetic multipole order. While this spontaneous order leavesPTsymmetry intact, the simultaneous violation ofPandTsymmetries gives rise to various emergent responses that are qualitatively different from those allowed by the nonmagneticP-symmetry breaking or by the ferromagnetic order. In this review, we introduce candidates hosting the intriguing spontaneous order and overview the characteristic physical responses. Various off-diagonal and/or nonreciprocal responses are identified, which are closely related to the unusual electronic structures such as hidden spin-momentum locking and asymmetric band dispersion.

Erratum: Attenuation of postprandial blood glucose in humans consuming isomaltodextrin: carbohydrate loading studies.

[This corrects the article DOI: 10.1080/16546628.2017.1325306.].

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.

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.

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.].

[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.

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.

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.