Efficacy and safety of chemoimmunotherapy in advanced non-small cell lung cancer patients with antibiotics-induced dysbiosis: a propensity-matched real-world analysis.

PURPOSE: The gut microbiota is hypothesized as a prognostic biomarker for cancer immunotherapy. Antibiotic-induced dysbiosis negatively affects the clinical outcomes of immunotherapy. However, the effect of dysbiosis on the efficacy and safety of Chemoimmunotherapy (chemo-IOs), the frontline standard of care, in advanced non-small cell lung cancer (NSCLC) remains unknown. We aimed to compare the efficacy and safety of chemo-IOs in patients exposed to antibiotics before treatment with those of patients who were not exposed. METHODS: We retrospectively reviewed patients with advanced NSCLC treated with first-line chemo-IOs between 2018 and 2020 at the National Cancer Center Hospital. The patients were divided into two groups: those exposed to antibiotics within 30 days before induction therapy (ABx group) and those did not antibiotics (Non-ABx group). Propensity score matching was used to control for potential confounding factors. Clinical outcomes including progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were compared. RESULTS: Of 201 eligible patients, 21 were in the ABx group, and 42 were in the non-ABx group after propensity score matching. No differences in PFS or OS emerged between the two groups (ABx group vs. Non-ABx group) (PFS:7.0 months vs. 6.4 months, hazard ratio [HR] 0.89; 95% confidence interval [CI], 0.49-1.63, OS:20.4 months vs. 20.1 months, HR 0.87; 95% CI 0.44-1.71). The frequency of irAEs before propensity score matching was similar across any-grade irAEs (39.4% vs. 42.9%) or grade 3 or higher irAEs (9.1% vs. 11.3%). CONCLUSION: Antibiotic-induced dysbiosis may not affect the efficacy of chemo-IOs in patients with advanced NSCLC.

A first-in-man study of [18F] FEDAC: a novel PET tracer for the 18-kDa translocator protein.

PURPOSE: N-benzyl-N-methyl-2-[7, 8-dihydro-7-(2-[18F] fluoroethyl) -8-oxo-2-phenyl-9H-purin-9-yl] acetamide ([18F] FEDAC) is a novel positron emission tomography (PET) tracer that targets the translocator protein (TSPO; 18 kDa) in the mitochondrial outer membrane, which is known to be upregulated in various diseases such as malignant tumors, neurodegenerative diseases, and neuroinflammation. This study presents the first attempt to use [18F]FEDAC PET/CT and evaluate its biodistribution as well as the systemic radiation exposure to the radiotracer in humans. MATERIALS AND METHODS: Seventeen whole-body [18F]FEDAC PET/CT (injected dose, 209.1 ± 6.2 MBq) scans with a dynamic scan of the upper abdomen were performed in seven participants. Volumes of interest were assigned to each organ, and a time-activity curve was created to evaluate the biodistribution of the radiotracer. The effective dose was calculated using IDAC-Dose 2.1. RESULTS: Immediately after the intravenous injection, the radiotracer accumulated significantly in the liver and was subsequently excreted into the gastrointestinal tract through the biliary tract. It also showed high levels of accumulation in the kidneys, but showed minimal migration to the urinary bladder. Thus, the liver was the principal organ that eliminated [18F] FEDAC. Accumulation in the normal brain tissue was minimal. The effective dose estimated from biodistribution in humans was 19.47 ± 1.08 µSv/MBq, and was 3.60 mSV for 185 MBq dose. CONCLUSION: [18F]FEDAC PET/CT provided adequate image quality at an acceptable effective dose with no adverse effects. Therefore, [18F]FEDAC may be useful in human TSPO-PET imaging.

Engineering yeast with a light-driven proton pump system in the vacuolar membrane.

BACKGROUND: The supply of ATP is a limiting factor for cellular metabolism. Therefore, cell factories require a sufficient ATP supply to drive metabolism for efficient bioproduction. In the current study, a light-driven proton pump in the vacuolar membrane was constructed in yeast to reduce the ATP consumption required by V-ATPase to maintain the acidification of the vacuoles and increase the intracellular ATP supply for bioproduction. RESULTS: Delta rhodopsin (dR), a microbial light-driven proton-pumping rhodopsin from Haloterrigena turkmenica, was expressed and localized in the vacuolar membrane of Saccharomyces cerevisiae by conjugation with a vacuolar membrane-localized protein. Vacuoles with dR were isolated from S. cerevisiae, and the light-driven proton pumping activity was evaluated based on the pH change outside the vacuoles. A light-induced increase in the intracellular ATP content was observed in yeast harboring vacuoles with dR. CONCLUSIONS: Yeast harboring the light-driven proton pump in the vacuolar membrane developed in this study are a potential optoenergetic cell factory suitable for various bioproduction applications.

Intraoperative motor-evoked potential with tetanic stimulation changes pre- and post-hemispherotomy.

BACKGROUND: Careful examination of motor-evoked potential (MEP) findings is critical to the safety of intraoperative neuromonitoring during neurosurgery. We reviewed the intraoperative MEP findings in a pediatric patient who had undergone hemispherotomy for refractory epilepsy. CASE DESCRIPTION: The patient was a 4-year-and-2-month-old boy with extensive right cerebral hemisphere, drug-resistant epilepsy, left upper and lower extremity paralysis, and cognitive impairment. We examined intraoperative MEP results both before and after hemispherotomy. Post-hemispherotomy and MEPs were successfully elicited through transcranial electrical stimulation (TES) but not via direct cortical stimulation on the right side. Furthermore, TES on the right side, following hemispherotomy, led to a reduction in the MEP amplification effect resulting from tetanic stimulation of the left unilateral median and tibial nerves. Conversely, we observed the effects of MEP amplification during TES on the left side after tetanic stimulation of these nerves. Postoperatively, the patient underwent magnetic resonance imaging and electroencephalogram examinations, confirming the anatomical and electrophysiological completeness of the dissection. Notably, the seizures disappeared, and no apparent complications were observed. CONCLUSION: Collectively, our findings suggest that TES can still activate deep structures and elicit MEPs, even in cases where the corticospinal connections to the posterior limb of the internal capsule are entirely severed. Thalamo-cortical interactions may affect the MEP amplification, observed during tetanic stimulation. Injury to the corticospinal tracts of the white matter may be obscured on conventional MEP findings; however, it may be identified by MEP changes in tetanic stimulation.

Case report: Giant pituitary neuroendocrine tumor presented along with acute visual loss due to pituitary apoplexy after receiving COVID-19 vaccination.

Objective: A case of giant pituitary neuroendocrine tumor presented along with acute visual loss due to pituitary apoplexy after receiving a COVID-19 vaccination is reported. Case presentation: A 45-year-old man was referred for a giant pituitary tumor with bitemporal hemianopsia. A surgical procedure was planned and then delayed due to the COVID-19 outbreak in Japan, with a Pfizer/BioNTech vaccine administered while awaiting surgery. Three days after the second COVID-19 vaccination the patient noted a progressively worsening headache that caused pituitary apoplexy and then a decrease in vision. Emergency surgery was thus performed. Conclusion: Pituitary apoplexy is a rare and life-threatening complication that may occur after undergoing a COVID-19 vaccination.

Imaging Features of Ectopic Tissues and Their Complications: Embryologic and Anatomic Approach.

Ectopic tissue is an anatomic abnormality in which tissue develops in an area outside its normal location. It is primarily caused by abnormalities during the process of embryologic development. Although the majority of individuals with ectopic tissues remain asymptomatic, various symptoms and associated complications can occur. Failure in normal embryologic development leads to loss of normal physiologic function or may result in harmful functions such as ectopic hormonal secretion in the ectopic pituitary adenoma. Ectopic tissues may also frequently mimic tumors. For example, developmental abnormalities in the pharyngeal pouches may result in an ectopic parathyroid gland and ectopic thymus, both of which are frequently misdiagnosed as tumors. Adequate knowledge of embryology is essential for understanding the differential diagnoses of ectopic tissues and facilitating appropriate management. The authors summarize the embryologic development and pathogenesis of ectopic tissues by using illustrations to facilitate a deeper understanding of embryologic development and anatomy. Characteristic imaging findings (US, CT, MRI, and scintigraphy) are described for ectopic tissues of the brain, head, neck, thorax, abdomen, and pelvis by focusing on common conditions that radiologists may encounter in daily practice and their differential diagnoses. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

Mucoepidermoid carcinoma cured by a combination of high-frequency snare and photodynamic therapy: A case report.

Mucoepidermoid carcinoma (MEC) is a rare salivary gland tumor, accounting for 0.2% of all lung tumors. The standard treatment for MEC of the primary bronchus is surgery, although intraluminal bronchoscopic treatment has recently become an option. A 68-year-old man presented with an asymptomatic bronchial tumor in the right intermediate bronchus. The tumor was resected using a high-frequency snare (HFS) during bronchoscopy, and the specimen was pathologically diagnosed as low-grade MEC. A residual lesion was detected in the resected area by autofluorescence imaging. The tumor appeared to be localized within the subepithelial layer without metastases, and photodynamic therapy (PDT) was performed as a local treatment. The patient had no recurrence for 18 months. PDT is effective and safe for patients with centrally located early-stage lung cancer, but there are few reports of its use for rare tumors, such as MEC. In this case, PDT allowed for local control and avoided surgery, including bronchoplasty, for MEC. Combined treatment of tumor reduction by HFS and PDT of the residual lesion may be an optimal treatment for MEC of the bronchus.

Biosynthetic Gene Expression and Tissue Distribution of Diosgenin in Dioscorea japonica.

Diosgenin is an aglycone of dioscin, a major bioactive steroidal saponin found in plants, including Himalayan Paris (Paris polyphylla), fenugreek (Trigonella foenum-graecum), and yam (Dioscorea spp.). We have previously demonstrated that a species of natural yam, Dioscorea japonica, contains a promising bioactive compound diosgenin, which induces anti-carcinogenic and anti-hypertriacylglycerolemic activities. Here, we found for the first time that Japanese yam (D. japonica) bulbils are richer in diosgenin than the edible tubers (rhizomes) and leaves. LC-MS and imaging-MS analyses revealed that diosgenin accumulated in the peripheral region of D. japonica bulbils. Additionally, we performed RNA-seq analysis of D. japonica, and multiple sequence alignment identified D. japonica CYP90 (DjCYP90), the orthologous gene of CYP90G4 in P. polyphylla, CYP90B50 in T. foenum-graecum, CYP90G6 in Dioscorea zingiberensis, and CYP90G in Dioscorea villosa, which encodes a diosgenin biosynthetic rate-limiting enzyme. The expression levels of DjCYP90 were significantly upregulated in D. japonica bulbils than in its rhizomes and leaves. Since diosgenin is one of the most promising functional food factors executing several favorable bioactivities, D. japonica bulbils rich in diosgenin would be a beneficial natural resource.

Perioperative Management of Congenital Diaphragmatic Hernia Repair in a Patient With Univentricular Circulation: A Case Report.

The survival rate in congenital diaphragmatic hernia (CDH) with complex heart defects is low. Although the current consensus on the indications for surgical repair of CDH without heart defects has improved surgical outcomes, the surgical indication for CDH with complex heart defects remains unclear. Herein, we report the perioperative management of a patient with univentricular circulation who underwent CDH repair. Thus, patients with CDH complicated by univentricular anatomy may tolerate surgery depending on preserved respiratory function.

Intraoperative Ventricular Opening has No Effect on Complication Development Following BCNU Wafer Implantation for Malignant Glioma.

OBJECTIVE: To evaluate the safety profile of bis-chloroethyl-nitrosourea (BCNU) wafer implantation after malignant glioma resection with or without ventricular opening (VO). METHODS: This single-center retrospective study included 66 consecutive patients with BCNU wafer implantation after malignant glioma resection between March 2013 and August 2021. The patients were categorized into 2 groups based on whether VO occurred during the malignant glioma resection. Fifty-eight patients had glioblastoma, and 8 had anaplastic astrocytoma or oligodendroglioma. Forty-eight patients underwent an initial treatment, and 18 underwent recurrent surgeries. Infection, hydrocephalus, subcutaneous fluid collection, chronic subdural hematoma, early seizure after surgery within 1 month, symptomatic edema surrounding the resected cavity, cyst formation, and postoperative hemorrhage were defined as adverse events (AEs). RESULTS: Thirty-three patients underwent resection with VO, and 33 without. The median survival time was 28 months in the initial treatment group and 11.5 months in the recurrent treatment group. The with and without VO groups had similar median survival times. Postoperative AEs occurred in 7/33 patients (21.2%) with VO and 10/33 (30.3%) without VO, with no difference between them (P = 0.574). CONCLUSIONS: This study showed that VO during surgery with BCNU wafer implantation might not influence the occurrence of postoperative AEs. If VO happens, BCNU wafer implantation can be performed safely with accurate closing of the ventricle.

Estimation of post-therapeutic liver reserve capacity using 99mTc-GSA scintigraphy prior to carbon-ion radiotherapy for liver tumors.

BACKGROUND: There is currently no established imaging method for assessing liver reserve capacity prior to carbon-ion radiotherapy (CIRT) for liver tumors. In order to perform safe CIRT, it is essential to estimate the post-therapeutic residual reserve capacity of the liver. PURPOSE: To evaluate the ability of pre-treatment 99mTc-galactosyl human serum albumin (99mTc-GSA) scintigraphy to accurately estimate the residual liver reserve capacity in patients treated with CIRT for liver tumors. MATERIALS AND METHODS: This retrospective study evaluated patients who were performed CIRT for liver tumors between December 2018 and September 2020 and underwent 99mTc-GSA scintigraphy before and 3 months after CIRT, and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI within 1 month before CIRT were evaluated. The maximal removal rate of 99mTc-GSA (GSA-Rmax) was analyzed for the evaluation of pre-treatment liver reserve capacity. Then, the GSA-Rmax of the estimated residual liver (GSA-RL) was calculated using liver SPECT images fused with the Gd-EOB-DTPA-enhanced MRI. GSA-RL before CIRT and GSA-Rmax at 3 months after CIRT were compared using non-parametric Wilcoxon signed-rank test and linear regression analysis. RESULTS: Overall, 50 patients were included (mean age ± standard deviation, 73 years ± 11; range, 29-89 years, 35 men). The median GSA-RL was 0.393 [range, 0.057-0.729] mg/min, and the median GSA-Rmax after CIRT was 0.369 [range, 0.037-0.780] mg/min (P = .40). The linear regression equation representing the relationship between the GSA-RL and GSA-Rmax after CIRT was y = 0.05 + 0.84x (R2 = 0.67, P < .0001). There was a linear relationship between the estimated and actual post-treatment values for all patients, as well as in the group with impaired liver reserve capacity (y = - 0.02 + 1.09x (R2 = 0.62, P = .0005)). CONCLUSIONS: 99mTc-GSA scintigraphy has potential clinical utility for estimating the residual liver reserve capacity in patients undergoing carbon-ion radiotherapy for liver tumors. TRIAL REGISTRATION: UMIN000038328, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000043545 .

Prevalence of infectious diseases in preterm infants: a 2-year follow-up from the Japan Environment and Children's Study.

Evidence regarding the long-term risk of infections in preterm infants is lacking. In this study, we examined whether preterm infants developed various common childhood infections more frequently than full-term infants by the age of 2 years by analyzing data from a questionnaire completed by 67,282 mother-toddler pairs in a nationwide birth cohort study. Of the target population, 2885 (4.3%) were born prematurely. After covariate adjustment for maternal and children factors, lower respiratory tract infections appeared more frequent in preterm than in full-term infants at both 1 and 2 years (adjusted odds ratio [aOR] 1.21, 95% confidence interval [CI] 1.05-1.41, and aOR 1.27, 95% CI 1.11-1.46, respectively). However, there was no significant difference in the frequencies of lower respiratory tract infection between preterm and full-term infants after Palivizumab administration. The risk of other common infections, such as in the upper respiratory tract infection, otitis media, urinary tract infection, gastroenteritis, herpangina, hand-foot-and-mouth disease, chickenpox, influenza virus, and adenovirus infections, was not higher in preterm than in full-term infants after covariates adjustment for maternal and children factors. These findings suggest Palivizumab prophylaxis could reduce the frequencies of lower respiratory tract infection in preterm to the same level as in full-term infants.

[S-methyl-11C]-L-methionine positron emission tomography/computed tomography imaging parameters to evaluate early response for esophageal cancer with neoadjuvant carbon ion radiotherapy.

This study aimed to evaluate the uptake of the clinical effectiveness of [S-methyl-11C]-L-methionine positron emission tomography/computed tomography (MET PET/CT) in patients with esophageal cancer and to investigate MET PET/CT imaging parameters to assess early response for esophageal cancer with neoadjuvant carbon ion radiotherapy (CIRT). MET PET/CT scans were performed in nineteen patients before and 3 weeks after completion of CIRT. After Surgery, the effect of neoadjuvant CIRT was investigated by examining the relationship between each parameter of MET uptake and the histological assessment (grade and tumor residual ratio). Four parameters of MET uptake were the maximum and minimum standardized uptake values of pre and post CIRT (pre-SUVmax, pre-SUVmean, post-SUVmax, and post-SUVmean). MET PET/CT imaging of esophageal cancer was clearly demonstrated. The post-SUVmax was the most suitable parameter. When the cutoff value was set as post-SUVmax = 6.21, the sensitivity, the specificity, and the accuracy of Grades 3 were 100.0%, 63.6%, and 78.9%, respectively. And there was a positive relationship between the tumor residual ratio and post-SUVmax (R2 = 0.38, p < 0.005). MET PET/CT is clinically useful for the assessment of early response to neoadjuvant CIRT in esophageal cancer. Particularly, post-SUVmax is considered a promising PET imaging parameter.

Impact of surgical factors on delayed hyponatremia in patients with nonfunctioning pituitary adenoma after endonasal endoscopic transsphenoidal procedure.

PURPOSE: Delayed hyponatremia can occur after pituitary surgery, resulting in prolonged hospitalization. However, the influence of surgical factors after such a procedure has not been well established. The impact of surgery and related factors on delayed hyponatremia was investigated. METHODS: This was a retrospective analysis of 137 consecutive patients who underwent transsphenoidal surgery for a nonfunctioning pituitary adenoma between 2008 and 2019. Preoperative (demographics, comorbidities), intraoperative (resection extent, operation time, blood loss volume, cerebrospinal fluid leak, tumor consistency), and postoperative [hematoma, meningitis, diabetes insipidus (DI), hormonal assessment] data were collected, with statistical analysis of each factor performed. RESULTS: Among the 137 patients, delayed hyponatremia occurred in 31 (22.6%). Multivariate analysis revealed that those with hypertension had a significantly higher likelihood of avoiding delayed hyponatremia (p = 0.004). Although no correlations of direct surgical factors with delayed hyponatremia were found, multivariate analysis of indirect surgical factors showed that presence of a firm tumor, transient DI, and meningitis were significantly associated with delayed hyponatremia (p = 0.014, 0.001, and 0.047, respectively). There was also a significant association of severe hyponatremia with appearance of symptoms (p = 0.002). CONCLUSION: There was a tendency for hypertension to be associated with delayed hyponatremia avoidance, with indirect surgical factors including tumor consistency, transient DI, and meningitis found to have an influence on delayed hyponatremia. It was concluded that attention should be given to non-hypertensive patients with a firm tumor, transient DI, or meningitis after pituitary surgery, as delayed hyponatremia may occur.

Effects of postnatal hydrocortisone on cytokine profile in extremely preterm infants.

BACKGROUND: Systemic hydrocortisone administration has been widely used in preterm infants who are at risk of bronchopulmonary dysplasia (BPD). However, the effects of hydrocortisone on cytokine profiles have not been examined. We aimed to investigate the effects of postnatal hydrocortisone treatment on serum cytokine levels in extremely preterm infants. METHODS: This is a retrospective study of 29 extremely preterm infants born at <28 weeks of gestational age. We obtained serum from blood samples collected during an early phase (5-20 days) and a late phase (28-60 days) after birth. We measured the levels of proinflammatory cytokines (tumor necrosis factors α and ß, interleukin (IL)-1ß, and IL-6), T-helper (Th) 1 cytokines (interferon-γ, IL-2, and IL-12p70), Th2 cytokines (IL-4, IL-5, and IL-10), Th17 cytokine IL-17A, and chemokine IL-8. The cytokine levels between the early and late phases were compared between infants who received postnatal hydrocortisone and those who did not. RESULTS: Thirteen infants (45%) received systemic hydrocortisone treatment at a median age of 15 days (IQR: 10.0-21.5) after birth due to respiratory deterioration. The percentage of BPD was higher in the steroid group than in the non-steroid group (P = 0.008). The ratio of IL-6 for the late-to-early phase was significantly lower in the steroid group than in the non-steroid group (P = 0.04). The concentration of the other cytokines remained unchanged between the phases. CONCLUSIONS: Although the postnatal hydrocortisone treatment provided for respiratory deterioration did not prevent the BPD development, hydrocortisone treatment might suppress IL-6 overproduction in extremely preterm infants.

[Bentall Operation for Pregnant Women with Marfan's Syndrome].

A 35-years-old pregnant woman with Marfan's syndrome visited the emergent department. She had sudden severe back pain. She was at the 20th week of gestation. An emergent chest computed tomo-graphy scan showed Stanford type B acute aortic dissection. After admission, strict blood pressure control was started. According to aortic valve insufficiency and fluid retention with pregnancy, acute heart and respiratory failure was getting worse. It seemed risky for both mother and the fetus to continue pregnancy. After sincere and detailed discussion between the patient and our multidisciplinary medical team, the patient decided to continue pregnancy. An urgent Bentall operation was performed. A careful attention was paid for the fetus during and after the surgery. Strict blood pressure control was also continued. The mother and the 30-week-gestation newborn recovered uneventfully. During four years of follow-up, thoracic and thoraco-abdominal aortic replacement was performed. The patient survived all of these procedures without any complication.

Validation of Nuclear Pore Complex Protein-Protein Interactions by Transient Expression in Plants.

The nuclear pore complex (NPC) is the largest protein complex, consisting of multiple copies of over 30 different nucleoporins. The interactions between the nucleoporins are critical elements for the NPC functions of the nuclear envelope in plant cells. In recent years, transient expression-based validations of protein-protein interactions have been widely used in plants. Bimolecular fluorescence complementation assay and coimmunoprecipitation assays are powerful tools to identify the molecules that interact with specific proteins. Here, as an example, we describe these techniques using nucleoporin protein interactions in plants.

Linac-based stereotactic radiosurgery and fractionated stereotactic radiotherapy with a micro-multileaf collimator for brain metastasis in the primary motor cortex.

This study aimed to assess the clinical outcomes of linear accelerators (linac)-based, stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for brain metastasis in the primary motor cortex (BMPMC). Thirty-five consecutive patients with BMPMC who were treated by linac-based SRS or fSRT between January 2012 and March 2020 were analyzed. BMPMC was defined as a tumor located in the precentral gyrus on gadolinium-enhanced magnetic resonance imaging (MRI) and T2-weghted imaging (T2WI). In total, 35 patients with 37 metastases were analyzed. The median follow-up time was 13 (range: 1-97) months. The tumor volume was 0.05-26.5 (median: 0.62) cm3. All patients were treated with SRS or fSRT using 35 Gy with 7 Gy per fraction daily. The median survival time (MST) was 16.9 months. The pretreatment KPS and RPA class significantly differed in terms of MST on the log-rank tests. Seven symptomatic patients had hemiparesis before SRS or fSRT. All symptomatic patients, except one with facial paresis and one who died within 3 months, experienced improvement at a 3 month follow-up. None of the patients presented with persistent radiation injury at the final follow-up. Two patients presented with grade 3 radiation-related central nervous system necrosis, which was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. In BMPMC, SRS and fSRT had good tumor control and did not cause serious complications. Therefore, they are suitable treatment options with an acceptable safety profile.

Comprehensive analysis of peptide-coding genes and initial characterization of an LRR-only microprotein in Marchantia polymorpha.

In the past two decades, many plant peptides have been found to play crucial roles in various biological events by mediating cell-to-cell communications. However, a large number of small open reading frames (sORFs) or short genes capable of encoding peptides remain uncharacterized. In this study, we examined several candidate genes for peptides conserved between two model plants: Arabidopsis thaliana and Marchantia polymorpha. We examined their expression pattern in M. polymorpha and subcellular localization using a transient assay with Nicotiana benthamiana. We found that one candidate, MpSGF10B, was expressed in meristems, gemma cups, and male reproductive organs called antheridiophores. MpSGF10B has an N-terminal signal peptide followed by two leucine-rich repeat (LRR) domains and was secreted to the extracellular region in N. benthamiana and M. polymorpha. Compared with the wild type, two independent Mpsgf10b mutants had a slightly increased number of antheridiophores. It was revealed in gene ontology enrichment analysis that MpSGF10B was significantly co-expressed with genes related to cell cycle and development. These results suggest that MpSGF10B may be involved in the reproductive development of M. polymorpha. Our research should shed light on the unknown role of LRR-only proteins in land plants.

Salvage Surgical Resection after Linac-Based Stereotactic Radiosurgery for Newly Diagnosed Brain Metastasis.

BACKGROUND: This study aimed to assess the clinical outcomes of salvage surgical resection (SSR) after stereotactic radiosurgery and fractionated stereotactic radiotherapy (SRS/fSRT) for newly diagnosed brain metastasis. METHODS: Between November 2009 and May 2020, 318 consecutive patients with 1114 brain metastases were treated with SRS/fSRT for newly diagnosed brain metastasis at our hospital. During this study period, 21 of 318 patients (6.6%) and 21 of 1114 brain metastases (1.9%) went on to receive SSR after SRS/fSRT. Three patients underwent multiple surgical resections. Twenty-one consecutive patients underwent twenty-four SSRs. RESULTS: The median time from initial SRS/fSRT to SSR was 14 months (range: 2-96 months). The median follow-up after SSR was 17 months (range: 2-78 months). The range of tumor volume at initial SRS/fSRT was 0.12-21.46 cm3 (median: 1.02 cm3). Histopathological diagnosis after SSR was recurrence in 15 cases, and radiation necrosis (RN) or cyst formation in 6 cases. The time from SRS/fSRT to SSR was shorter in the recurrence than in the RNs and cyst formation, but these differences did not reach statistical significance (p = 0.067). The median survival time from SSR and from initial SRS/fSRT was 17 and 74 months, respectively. The cases with recurrence had a shorter survival time from initial SRS/fSRT than those without recurrence (p = 0.061). CONCLUSIONS: The patients treated with SRS/fSRT for brain metastasis need long-term follow-up. SSR is a safe and effective treatment for the recurrence, RN, and cyst formation after SRS/fSRT for brain metastasis.