Biological characterization and genomic analysis of a novel bacteriophage, MopsHU1, infecting Morganella psychrotolerans.

Morganella psychrotolerans is a histamine-producing bacterium that causes histamine poisoning. In this study, we isolated and characterized a novel phage, MopsHU1, that infects M. psychrotolerans. MopsHU1 is a podovirus with a limited host spectrum. Genomic analysis showed that MopsHU1 belongs to the family Autographiviridae, subfamily Studiervirinae, and genus Kayfunavirus. Comparative analysis revealed that the MopsHU1 genome is similar to those of Citrobacter phage SH3 and Cronobacter phage Dev2. Moreover, the Escherichia coli phage K1F genome is also similar, except for its tailspike gene sequence. These results expand our understanding of the Kayfunavirus phages that infect Morganella spp. Note: The nucleotide sequence data reported here are available in the DDBJ/EMBL/GenBank database under the accession number LC799501.

Impact of timing and initial recurrence site on post-recurrence survival in resected non-small cell lung cancer.

INTRODUCTION: High recurrence rate following curative surgery for non-small cell lung cancer (NSCLC) presents a major clinical challenge. Understanding the site and timing of recurrence and their impact on post-recurrence survival (PRS) is important for optimal postoperative surveillance and therapeutic intervention. In this study, we investigated the influence of the time to recurrence (TTR) and initial recurrence site on PRS. MATERIALS AND METHODS: This multicentre prospective cohort study included patients who experienced recurrence after NSCLC resection between 2010 and 2015. The relationship between TTR and initial recurrence site, and their impact on PRS, was further evaluated. The hazard ratio (HR) for PRS was analysed using the Cox proportional hazards model. RESULTS: Among 495 patients, the median TTR was 14 (range, 1-158) months; the mode of recurrence was 11 months. Early recurrence within 6 months was observed in 17 % of patients, and 68 % of patients showed recurrence within 2 years post-surgery. The HR for PRS was the highest in patients with a TTR within 6 months, and a noticeable decline was observed after the first 6 months. The HRs of TTRs beyond 2 years were not significantly different. The liver was a significantly unfavourable prognostic site for metastases (HR 2.2; P = 0.01), and metastases frequently recurred within 6 months after surgery. The timing of brain metastasis did not significantly impact the PRS. CONCLUSION: Earlier recurrence after surgery was associated with shorter PRS. In contrast, recurrences occurring >2 years after surgery do not significantly affect PRS.

Baseline genetic abnormalities and effectiveness of osimertinib treatment in patients with chemotherapy-naïve EGFR-mutated NSCLC based on performance status.

BACKGROUND/AIM: For patients treated with osimertinib as first-line therapy, there have been no studies comparing both progression-free survival (PFS) and overall survival (OS) according to performance status (PS). Furthermore, no studies have examined differences in baseline genetic abnormalities between patients with poor and good PS. Therefore, we aimed to investigate differences in baseline genetic abnormalities and treatment effects between patients with poor and good PS who received osimertinib as the primary treatment. PATIENTS AND METHODS: This is a secondary analysis of the ELUCIDATOR study, which is a multi-center prospective observational study in Japan that assessed mechanisms underlying resistance to osimertinib as first-line treatment for advanced non-small cell lung cancer with epidermal growth factor receptor mutations. RESULTS: There were 153 and 25 patients in the good and poor PS groups, respectively. Multivariate analysis revealed no significant between-group differences in PFS (hazards ratio [HR]: 0.98, 95% confidence interval [CI]: 0.52-1.72, p = 0.946). Multivariate analysis of OS revealed that poor PS was a poor prognostic factor (HR: 2.67, 95% CI: 1.43-4.73, p = 0.003). Regarding baseline genetic abnormalities, there was a significant increase in APC-positive cases (20.0% vs. 2.2%, p = 0.009) and a trend toward more CTNNB1-positive cases in the poor PS group than in the good PS group (14.3% vs. 2.9%, p = 0.062). CONCLUSION: There was no between-group difference in PFS, although OS was significantly inferior in the poor PS group. Additionally, there was a significant increase in APC-positive cases and a trend toward more CTNNB1-positive cases in the poor PS group.

Mechanisms of resistance and correlation between pre-treatment co-alterations and p-prognosis to osimertinib in chemo-naïve advanced non-small cell lung cancer.

BACKGROUND: Several patients treated with osimertinib experience progressive disease. The aim was to clarify the mechanisms underlying resistance to osimertinib. METHODS: ELUCIDATOR: A multi-centre, prospective, observational study involved chemotherapy-naive patients with advanced non-small cell lung cancer receiving osimertinib. Mutations in cancer-associated genes, detected via ultrasensitive next-generation sequencing of circulating tumour deoxyribonucleic acid samples, were collected at baseline and after progressive disease detection. These paired plasma samples were compared. RESULTS: Of 188 patients enrolled (May 2019-January 2021), 178 (119 females [67 %]) median age 74 years, were included. Patients, n = 95 (53 %) had epidermal growth factor receptor exon 19 deletion mutations. Among 115 patients with progressive disease, circulating tumour deoxyribonucleic acid levels of 85 patients were analysed. MET amplification (n = 4), TP53 mutations (n = 4), PIK3CA mutations (n = 3), BRINP3 mutation (n = 2), BRAF mutation (n = 2), APC mutation (n = 1), RET mutation (n = 1) and epidermal growth factor receptor (EGFR) resistance mutation, and C797S (n = 1) were detected. Patients with baseline TP53 mutations, with MET or EGFR amplification had shorter progression-free (PFS) and overall survival. Patients with PIK3CA mutations tended to shorter PFS. CONCLUSION: MET amplification and PIK3CA mutation mechanisms underly resistance to osimertinib in patients. Patients with coexisting mutations or amplifications at baseline had shorter PFS and overall survival.

Removal of a Metallic Stent after 9 Years of Placement That Caused Tracheal Stenosis: A Rare Case Report.

Introduction: Metallic stents are widely used to prevent airway obstruction for tracheal stenosis caused by malignant diseases. Although their efficacy has been recognized, there is no established evidence surrounding their long-term safety. We report a case of airway stenosis caused by a metallic tracheal stent. Removal of the stent to secure the airway was difficult and extremely complicated. Case Presentation: A 50-year-old male suffering from dyspnea caused by malignant lymphoma (diffuse large B-cell lymphoma) of the thyroid gland was treated with a metallic tracheal stent. After remission of the lymphoma, stenosis of the stent lumen developed gradually, and the patient complained of dyspnea. Tracheostomy could not be performed due to the metallic stent. Since the patient was unable to intubate, the stent was removed under general anesthesia with partial percutaneous cardiopulmonary support 9 years after the stent placement. Conclusion: Otolaryngologists should be aware of the possibility of severe stenosis following the long-term placement of a metallic tracheal stent.

Five-Year Overall Survival Analysis of the JIPANG Study: Pemetrexed or Vinorelbine Plus Cisplatin for Resected Stage II-IIIA Nonsquamous Non-Small-Cell Lung Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The JIPANG study is an open-label phase III trial evaluating the efficacy of pemetrexed plus cisplatin (PemP) versus vinorelbine plus cisplatin (NP) as adjuvant chemotherapy in patients with stage II-IIIA nonsquamous non-small-cell lung cancer (NSCLC). Here, we report the long follow-up overall survival (OS) data. Eligible patients were randomly assigned to receive either PemP or NP. The primary end point was recurrence-free survival (RFS), and the secondary end point included OS. This analysis was performed using data collected 5 years after the last patient enrollment. Among 804 patients enrolled, 783 patients were eligible (384 for NP and 389 for PemP). The updated median RFS was 37.5 months in the NP arm and 43.4 months in the PemP arm with a hazard ratio of 0.95 (95% CI, 0.79 to 1.14). At a median follow-up of 77.3 months, the OS rates at 3 and 5 years were 84.1% and 75.6% versus 87.0% and 75.0% with a hazard ratio of 1.04 (95% CI, 0.81 to 1.34). This long-term follow-up analysis showed that PemP had similar efficacy to NP in both RFS and OS for this population, with one of the longest OS data compared with the historical data.

Modulation of host glutamine anabolism enhances the sensitivity of small cell lung cancer to chemotherapy.

Small cell lung cancer (SCLC) is one of the deadliest human cancers, with a 5-year survival rate of ∼7%. Here, we performed a targeted proteomics analysis of human SCLC samples and thereby identified hypoxanthine phosphoribosyltransferase 1 (HPRT1) in the salvage purine synthesis pathway as a factor that contributes to SCLC malignancy by promoting cell survival in a glutamine-starved environment. Inhibition of HPRT1 by 6-mercaptopurine (6-MP) in combination with methotrexate (MTX), which blocks the de novo purine synthesis pathway, attenuated the growth of SCLC in mouse xenograft models. Moreover, modulation of host glutamine anabolism with the glutamine synthetase inhibitor methionine sulfoximine (MSO) in combination with 6-MP and MTX treatment resulted in marked tumor suppression and prolongation of host survival. Our results thus suggest that modulation of host glutamine anabolism combined with simultaneous inhibition of the de novo and salvage purine synthesis pathways may be of therapeutic benefit for SCLC.

Prognostic Impact of Central Nervous System Recurrence After Surgery in Patients With Epidermal Growth Factor Receptor Mutation-positive Non-small-cell Lung Cancer.

BACKGROUND/AIM: Adjuvant therapy using third-generation tyrosine kinase inhibitors (TKI) demonstrated improved central nervous system (CNS) disease-free survival after surgery in patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, the prognostic impact of CNS recurrence in surgical patients remains unknown. We evaluated the effect of CNS recurrence on post-recurrence survival (PRS) in patients with postoperatively recurrent NSCLC. PATIENTS AND METHODS: We assessed the prognostic impact of CNS recurrence using a cohort from a prospective observational study (Kyushu University Lung Surgery Group Study 2: KLSS-2). Based on data from 340 patients in whom EGFR mutations were assessed among 498 total patients in the KLSS-2 cohort, factors related to CNS recurrence and prognosis after postoperative recurrence were analyzed. RESULTS: We noted no marked differences in the presence of EGFR mutations (p=0.14) between patients with CNS recurrence and those without CNS recurrence. Among the patients tested for EGFR mutations with stage IV recurrences (n=219), survival analysis of patients with EGFR mutations showed that the CNS group had a significantly poorer PRS than the no-CNS group (MST: 36.8 vs. 43.9 months, p=0.035). In multivariate survival analysis of stage IV EGFR mutation-positive cases, recurrence in multiple organs and recurrence of brain metastases were independent poor prognostic factors (hazard ratio=2.2, p=0.029; hazard ratio=3.2, p=0.0006, respectively). CONCLUSION: Postoperative CNS recurrence was associated with a poor prognosis among patients with EGFR mutation-positive lung cancer in the period when third-generation EGFR-TKIs were not available. In EGFR mutation-positive lung cancer, prevention of CNS recurrence after surgery may improve post-recurrence prognosis.

Is radical local therapy effective in postoperative recurrent EGFR-mutated non-small cell lung cancer?

BACKGROUND: Long-term survival can be achieved with radical local therapy in some cases of postoperative recurrence of non-small cell lung cancer (NSCLC). Here, we evaluated post-recurrence survival (PRS) after treatment of postoperative recurrent epidermal growth factor receptor (EGFR) mutated NSCLC and examined the effectiveness of radical local therapy. METHODS: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data (e.g., treatment and survival outcomes) were obtained and analyzed. RESULTS: From 2010 to 2015, 505 patients with recurrent NSCLC were enrolled into the study, and 154 EGFR mutation-positive cases were included. As the initial treatment for recurrence, 111 patients (72%) received chemotherapy, 14 (9%) received chemoradiotherapy, 14 (9%) received definitive radiotherapy, and seven (5%) received surgical resection. The remaining eight patients (5%) received supportive care. The median PRS and 5-year survival rates for all cases were 64 months and 53.2%, respectively. The 5-year survival rate according to the initial treatment was as follows: supportive care, 0%; chemotherapy, 53.3% and radical local therapy, 60.1%. The six patients who received radical local treatment remained recurrence-free for more than 3 years after recurrence with only initial treatment. CONCLUSIONS: Although radical local therapy may be curative in some patients, chemotherapy including EGFR-TKI treatment is expected to provide long-term survival comparable to that of radical local therapy.

Impact of the pretreatment prognostic nutritional index on the survival after first-line immunotherapy in non-small-cell lung cancer patients.

BACKGROUND: Immunotherapy has become a standard-of-care for patients with non-small-cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death-1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count. Although several groups reported its prognostic role in patients with NSCLC receiving a single ICI, there exist no reports which have demonstrated its role in the first-line ICI combined with or without chemotherapy. MATERIALS AND METHODS: Two-hundred and eighteen patients with NSCLC were included in the current study and received pembrolizumab alone or chemoimmunotherapy as the first-line therapy. Cutoff value of the pretreatment PNI was set as 42.17. RESULTS: Among 218 patients, 123 (56.4%) had a high PNI (≥42.17), while 95 (43.6%) had a low PNI (<42.17). A significant association was observed between the PNI and both the progression-free survival (PFS; hazard ratio [HR] = 0.67, 95% confidence interval [CI]: 0.51-0.88, p = 0.0021) and overall survival (OS; HR = 0.46, 95% CI: 0.32-0.67, p < 0.0001) in the entire population, respectively. The multivariate analysis identified the pretreatment PNI as an independent prognosticator for the PFS (p = 0.0011) and OS (p < 0.0001), and in patients receiving either pembrolizumab alone or chemoimmunotherapy, the pretreatment PNI remained an independent prognostic factor for the OS (p = 0.0270 and 0.0006, respectively). CONCLUSION: The PNI might help clinicians appropriately identifying patients with better treatment outcomes when receiving first-line ICI therapy.

Timing and distance of natal dispersal in Asian black bears.

Dispersal has important implications for population ecology and genetics of a species through redistribution of individuals. In most mammals, males leave their natal area before they reach sexual maturity, whereas females are commonly philopatric. Here, we investigate the patterns of natal dispersal in the Asian black bear (Ursus thibetanus) based on data from 550 bears (378 males, 172 females) captured or removed in Gunma and Tochigi prefectures on central Honshu Island, Japan in 2003-2018. We used genetic data and parentage analysis to investigate sex-biased differences in the distance of natal dispersal. We further investigated the age of dispersal using spatial autocorrelation analysis, that is, the change in the correlation between genetic and geographic distances in each sex and age group. Our results revealed that male dispersal distances (mean ± SE = 17.4 ± 3.5 km) were significantly farther than female distances (4.8 ± 1.7 km), and the results were not affected by years of mast failures, a prominent forage source for this population. Based on an average adult female home range radius of 1.8 km, 96% of the males and 50% of the females dispersed. In the spatial autocorrelation analysis, the changes in the relationship between genetic and geographic distances were more pronounced in males compared to females. Males seem to mostly disperse at age 3 regardless of mast productivity, and they gradually disperse far from their home range, but young and inexperienced males may return to their natal home range in years with poor food conditions. The results suggest that factors driving the dispersal process seem to be population structure-based instead of forage availability-based. In females, a significant genetic relationship was observed among all individuals in the group with a minimum age of 6 years within a distance of 2 km, which resulted in the formation of matrilineal assemblages.

Comparing information derived on food habits of a terrestrial carnivore between animal-borne video systems and fecal analyses methods.

In recent years, animal-borne video cameras have been used to identify the food habits of many species. However, the usefulness and difficulties of identifying food habits from animal-borne video cameras have not been sufficiently discussed in terrestrial mammals, especially large omnivores. The aim of this study is to compare the video analysis of foraging behavior by Asian black bears (Ursus thibetanus) acquired by camera collars with estimates from fecal analysis. We attached GPS collars equipped with video cameras to four adult Asian black bears in the Okutama mountains in central Japan from May to July 2018 and analyzed video clips for foraging behavior. Simultaneously, we collected bear feces in the same area to determine food habits. We found that using video analyses was advantageous to recognize foods, such as leaves or mammals, that were physically crushed or destroyed while bears chewed and digested foods, which are difficult to identify to species using fecal analyses. On the other hand, we found that camera collars are less likely to record food items that are infrequently or quickly ingested. Additionally, food items with a low frequency of occurrence and short foraging time per feeding were less likely to be detected when we increased the time between recorded clips. As one of the first applications of the video analysis method for bears, our study shows that video analysis can be an important method for revealing individual differences in diet. Although video analysis may have limitations for understanding the general foraging behavior of Asian black bears at the present stage, the accuracy of food habit data from camera collars can be improved by using it in combination with established techniques such as microscale behavior analyses.

A worldwide perspective on large carnivore attacks on humans.

Large carnivores have long fascinated human societies and have profound influences on ecosystems. However, their conservation represents one of the greatest challenges of our time, particularly where attacks on humans occur. Where human recreational and/or livelihood activities overlap with large carnivore ranges, conflicts can become particularly serious. Two different scenarios are responsible for such overlap: In some regions of the world, increasing human populations lead to extended encroachment into large carnivore ranges, which are subject to increasing contraction, fragmentation, and degradation. In other regions, human and large carnivore populations are expanding, thus exacerbating conflicts, especially in those areas where these species were extirpated and are now returning. We thus face the problem of learning how to live with species that can pose serious threats to humans. We collected a total of 5,440 large carnivore (Felidae, Canidae, and Ursidae; 12 species) attacks worldwide between 1950 and 2019. The number of reported attacks increased over time, especially in lower-income countries. Most attacks (68%) resulted in human injuries, whereas 32% were fatal. Although attack scenarios varied greatly within and among species, as well as in different areas of the world, factors triggering large carnivore attacks on humans largely depend on the socioeconomic context, with people being at risk mainly during recreational activities in high-income countries and during livelihood activities in low-income countries. The specific combination of local socioeconomic and ecological factors is thus a risky mix triggering large carnivore attacks on humans, whose circumstances and frequencies cannot only be ascribed to the animal species. This also implies that effective measures to reduce large carnivore attacks must also consider the diverse local ecological and social contexts.

Gut microbiota diversity and specific composition during immunotherapy in responders with non-small cell lung cancer.

Cancer immunotherapy including immune checkpoint inhibitors (ICI) has revolutionized non-small cell lung cancer (NSCLC) therapy. Recently, the microbiota status "before" initiation of ICI therapy has been emphasized as a predictive biomarker in patients undergoing ICI therapy. However, the microbiota diversity and composition "during" ICI therapy is unknown. This multicenter, prospective observational study analyzed both saliva and feces from 28 patients with NSCLC. We performed 16S ribosomal RNA gene sequencing, then analyzed associations of oral and gut microbiota diversity or composition with ICI response. At the genus level, the alpha diversity of the gut microbiota was significantly greater in responders (n = 17) than in non-responders (n = 11) (Chao 1, p = 0.0174; PD whole tree, p = 0.0219; observed species, p = 0.0238; Shannon, p = 0.0362), while the beta diversity of the gut microbiota was significantly different (principal coordinates analysis, p = 0.035). Compositional differences in the gut microbiota were observed between the two groups; in particular, g_Blautia was enriched in responders, whereas o_RF32 order unclassified was enriched in non-responders. The progression-free survival (PFS) of patients enriched gut microbiota of g_Blautia was significantly longer [median survival time (MST): not reached vs. 549 days, p = 0.0480] and the PFS of patients with gut microbiota of o_RF32 unclassified was significantly shorter (MST: 49 vs. 757 days, p = 0.0205). There were no significant differences between groups in the oral microbiota. This study revealed a strong association between gut microbiota diversity and ICI response in NSCLC patients. Moreover, specific gut microbiota compositions may influence the ICI response. These findings might be useful in identifying biomarkers to predict ICI response.

Carcass detection and consumption by facultative scavengers in forest ecosystem highlights the value of their ecosystem services.

Scavenging is a common feeding behavior that provides ecosystem services by removing potentially infectious waste from the landscape. The importance of facultative scavenging is often overlooked, but likely becomes especially important in ecosystems without obligate scavengers. Here, we investigated the ecological function of vertebrate facultative scavengers in removing ungulate carcasses from Japanese forests that lack obligate scavengers. We found that mammals detected carcasses first more often than birds, and that raccoon dogs (Nyctereutes procyonoides) were the most frequent scavenger to first detect carcasses. However, we found no evidence of there being species that signal the location of carrion to other species via social cues. Instead, higher temperatures promoted earlier detection of the carcasses by scavengers, likely related to increased olfactory signals. The carcasses were completely consumed on average in 7.0 days, reasonably similar to other systems regardless of habitat, indicating that facultative scavengers are providing ecosystem services. Larger carcasses tended to take longer to deplete, but carcasses were consumed faster in warmer temperatures. Our results indicate that facultative scavengers were capable of consuming carrion and contributing ecosystem services in a forest ecosystem that lacks obligate scavengers.

Chronological analysis of the gut microbiome for efficacy of atezolizumab-based immunotherapy in non-small cell lung cancer: Protocol for a multicenter prospective observational study.

BACKGROUND: Cancer immunotherapy with immune checkpoint inhibitors (ICIs) is an innovative treatment for non-small cell lung cancer (NSCLC). Recently, the specific composition of the gut microbiome before initiation of cancer immunotherapy has been highlighted as a predictive biomarker in patients undergoing cancer immunotherapy, mainly in the US or Europe. However, the fact gut microbiome status is completely different in races or countries has been revealed. In addition, how the microbiome composition and diversity chronologically change during cancer immunotherapy is still unclear. METHODS: This multicenter, prospective observational study will analyze the association between the gut microbiome and therapeutic response in NSCLC patients who received atezolizumab-based immunotherapy. The aim of the present study is to clarify not only how the specific composition of the gut microbiome influences clinical response in NSCLC patients but the chronological changes of gut microbiota during atezolizumab-based immunotherapy. The gut microbiota will be analyzed using 16S rRNA gene sequencing. The main inclusion criteria are as follows: (1) Pathologically- or cytologically-confirmed stage IV or postoperative recurrent NSCLC. (2) Patients ≥20 years old at the time of informed consent. (3) Planned to treat with atezolizumab-based immunotherapy combined with platinum-based chemotherapy (cohort 1) and monotherapy (cohort 2) as a first immunotherapy. (4) Patients to provide fecal samples. A total of 60 patients will be enrolled prospectively. Enrollment will begin in 2020 and the final analyses will be completed by 2024. DISCUSSION: This trial will provide more evidence of how gut microbiota composition and diversity chronologically change during cancer immunotherapy and contribute to the development of biomarkers to predict ICI response as well as biotic therapies which enhance the ICI response.

Survival after recurrence following surgical resected non-small cell lung cancer: A multicenter, prospective cohort study.

Objectives: The optimal treatment for recurrent non-small cell lung cancer (NSCLC) has not been standardized. In this prospective cohort study, we evaluated post-recurrence survival (PRS) after treatment of recurrent NSCLC and identified prognostic factors after recurrence. Methods: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data, such as treatment and survival outcomes, were obtained every 3 months. Results: From 2010 to 2015, 505 cases were enrolled, and 495 cases were analyzed. As initial treatment for recurrence, 263 patients (53%) received chemotherapy, 46 (9%) received chemoradiotherapy, 98 (20%) had definitive radiotherapy, 14 (3%) received palliative radiotherapy, and 31 (6%) underwent surgical resection. The remaining 43 patients (9%) received supportive care. The median PRS and 5-year survival rates for all cases were 30 months and 31.9%, respectively. The median PRS according to the initial treatment was as follows: supportive care, 8 months; palliative radiotherapy, 16 months; definitive radiotherapy, 30 months; chemotherapy, 31 months; chemoradiotherapy, 35 months; and surgery, not reached. A multivariate analysis showed that the age, gender, performance status, histology presence of symptoms, duration from primary surgery to recurrence, and number of recurrent foci were independent prognostic factors for PRS. Conclusions: The PRS of patients with recurrent NSCLC was different depending on the patient's background characteristics and initial treatment for recurrence.

Artificial intelligence-derived gut microbiome as a predictive biomarker for therapeutic response to immunotherapy in lung cancer: protocol for a multicentre, prospective, observational study.

INTRODUCTION: Immunotherapy is the fourth leading therapy for lung cancer following surgery, chemotherapy and radiotherapy. Recently, several studies have reported about the potential association between the gut microbiome and therapeutic response to immunotherapy. Nevertheless, the specific composition of the gut microbiome or combination of gut microbes that truly predict the efficacy of immunotherapy is not definitive. METHODS AND ANALYSIS: The present multicentre, prospective, observational study aims to discover the specific composition of the gut microbiome or combination of gut microbes predicting the therapeutic response to immunotherapy in lung cancer using artificial intelligence. The main inclusion criteria are as follows: (1) pathologically or cytologically confirmed metastatic or postoperative recurrent lung cancer including non-small cell lung cancer and small cell lung cancer; (2) age≥20 years at the time of informed consent; (3) planned treatment with immunotherapy including combination therapy and monotherapy, as the first-line immunotherapy; and (4) ability to provide faecal samples. In total, 400 patients will be enrolled prospectively. Enrolment will begin in 2021, and the final analyses will be completed by 2024. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review board of each participating centre in 2021 (Kyushu Cancer Center, IRB approved No. 2021-13, 8 June 2021 and Kyushu Medical Center, IRB approved No. 21-076, 31 August 2021). Study results will be disseminated through peer-reviewed journals and national and international conferences. TRIAL REGISTRATION NUMBER: UMIN000046428.

Broad host range bacteriophage, EscoHU1, infecting Escherichia coli O157:H7 and Salmonella enterica: Characterization, comparative genomics, and applications in food safety.

Shiga toxin-producing Escherichia coli and Salmonella enterica are important pathogens worldwide. Bacteriophages can be effectively used to reduce the incidence of foodborne pathogens. The host recognition systems of phages are highly specific, with the host range of a common phage being limited to the species or strain level. Here, we characterized a novel broad-host-range phage, EscoHU1, that infects several bacterial species, including E. coli and S. enterica, and evaluated its antimicrobial potential to inhibit E. coli O157:H7 and S. Typhimurium growth in food systems. The adsorption of EscoHU1 on E. coli was faster than that on S. Typhimurium; however, the one-step growth curves of EscoHU1 in both species were similar. Genomic analysis of EscoHU1 revealed that this phage has long direct terminal repeats at both ends of the genome, and phylogenetic analysis of the terminase large subunit confirmed that EscoHU1 belongs to the genus Epseptimavirus. Comparative analysis of structural proteins indicated a diversity of proteins related to the host range (receptor-binding proteins and L-shaped tail fibers). Challenge tests using beef and milk demonstrated the antimicrobial effects of EscoHU1 in inhibiting the growth of E. coli O157:H7 and S. Typhimurium in the food system. However, the antimicrobial effect of EscoHU1 on S. Typhimurium was lower than that on E. coli O157:H7. These results suggest that the novel broad-host-range phage EscoHU1 may serve as an effective antimicrobial agent to reduce food poisoning caused by E. coli O157:H7 and S. Typhimurium.

Robot-assisted thoracic surgery for intercostal cavernous hemangioma.

Intercostal cavernous hemangioma is extremely rare among benign vascular tumors. Achieving a definitive diagnosis preoperatively by radiographic examination alone is difficult; surgical resection is usually needed. Occasional cases are found as giant tumors, and some grow substantially during observation without treatment. Such tumors require extended surgical resection; however, small tumors can be completely resected by tumor extirpation alone. Thus, immediate surgical resection while the tumor is small might help to avoid invasive surgery. We herein describe cases of intercostal cavernous hemangioma with no invasion to the surrounding tissues, successfully treated by complete tumor resection using robot-assisted thoracic surgery.