bluuebunny/crossref_metadata_2025 huggingface dataset:
MPC-1 IMMUNOHISTOLOGICAL COMPREHENSIVE ANALYSIS OF ANGIOGENIC FACTORS OTHER THAN VEGF IN GLIOBLASTOMAS IN RELATION TO THE USE OF BEVACIZUMAB
Authors: Ezaki Taketo , Tamura Ryota , Tanaka Toshihide , Miyake Keisuke , Kuranari Yuki , Yamamoto Yohei , Takei Jun , Akasaki Yasuharu , Toda Masahiro , Murayama Yuichi , Tamiya Takashi , Sasaki Hikaru
Published: December 2022

To date, few clinical observations have been reported for changes of alternative angiogenic factors (other than vascular endothelial growth factor [VEGF]) in human gliomas under bevacizumab (Bev). The elucidation of the mechanism of action and resistance is imperative to overcome resistance to Bev and develop a more effective therapy. This study aims to investigate the status and change of alternative angiogenic factors regarding Bev usage.The present study used 56 glioblastoma tissues obtained at 3 different settings: tumors of initial resection (naive Bev group), tumors resected following Bev therapy (effective Bev group), and recurrent tumors after Bev therapy (refractory/autopsied Bev group). The expression of alternative angiogenic factors including basic fibroblast growth factor (bFGF), placental growth factor (PlGF), Angiopoietin1 (Ang-1), Angiopoietin2(Ang-2) and EphrinA2 were investigated via immunohistochemistry. In large tumor vasculature (diameter >15μm), the expression of PlGF was significantly higher in the effective Bev group than naive Bev group. The expression of Ang-2 was persistently suppressed in the refractory/autopsied Bev group. In microtumor vasculature (diameter <15μm), the expression of Ang-2 was higher in the effective group than naive Bev group. The status of PlGF was similar among these three groups.We provide the first clinicopathological evidence of the status of alternative angiogenic pathway after the Bev usage. These in situ observations will help to optimize therapy.
MPC-20 CLINICAL AND MOLECULAR FEATURES OF GLIOBLASTOMAS ARISING IN THE SETTING OF LI FRAUMENI SYNDROME
Authors: Kibe Yuji , Ohka Fumiharu , Aoki Kosuke , Motomura Kazuya , Yamaguchi Junya , Maeda Sachi , Nishikawa Tomohide , Shimizu Hiroki , Saito Ryuta
Published: December 2022

Introduction

Li Fraumeni Syndrome (LFS) is a rare autosomal dominant tumor predisposition syndrome caused by germline alterations of the TP53. Brain tumors are included in LFS core cancers. Choroid plexus carcinomas and medulloblastomas tend to present in pediatric LFS patients, while gliomas tend to present in adult LFS patients. There are few previous reports about gliomas arising in the setting of LFS. Here, we report clinical and molecular features of three cases of glioblastoma arising in the setting of LFS.

Results

Mean age at diagnosis was 40 years (range: 32-45). Two patients were male. Two patients had medical history of multiple tumors and family history of brain tumors. Magnetic resonance imaging of each patients revealed a left cerebellar peduncle lesion, a right parietal lobe lesion and two lesions in the pons and right parietal lobe, respectively. Pathological diagnoses of all cases were glioblastomas, IDH-wildtype. All patients underwent chemoradiotherapy after surgery. Mean progression free survival was 10.4 months (range: 5.1-17.0). All patients were admitted to palliative care mean 17.3 months (range: 14.4-21.4) after diagnosis. All patients had heterozygous germline mutations of TP53. Genetic analysis of tumor tissues revealed TP53 mutation and PDGFRA amplification in all patients. In all cases, mutation spots of TP53 in tumor-derived DNA were consistent with those of germ line mutations. In all cases, copy number alteration of TP53 gene in tumor-derived DNA were not detected. EGFR amplification, the combination of gain of chromosome 7 and loss of chromosome 10 (7+/10-) and mutations of IDH, H3F3A, BRAF genes and TERT gene promoter were not detected in all tumor-derived DNA.

Conclusion

We experienced three cases of glioblastoma, IDH-wildtype arising in the setting of LFS. Clinical courses of all cases were poor. Notably, all tumor tissues harbored TP53 mutation and PDGFRA amplification, while no tumor tissues harbored TERTp mutation, EGFR amplification and 7+/10-.
ML-12 HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM CELL TRANSPLANTATION (HDC-ASCT) FOR THE PATIENTS WITH PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL)
Authors: Miyakita Yasuji , Inamoto Yoshihiro , Ohno Makoto , Takahashi Masamichi , Yanagisawa Shunsuke , Kawaguchi Yuki , Mukai Takayuki , Masaki Yasufumi , Fukuda Takahiro , Narita Yoshitaka
Published: December 2022

High-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) for the patient with primary central nervous system lymphoma (PCNSL) has been used as treatment at relapse or as consolidation therapy. We report on the efficacy, safety, and future issues of HDC-ASCT. Twelve patients with PCNSL (10 males and 2 females) underwent HDC-ASCT, ranging in age from 45 to 66 years (median 58 years) and KPS from 70 to 100 (median 90) at the time of HDC-ASCT. HDC-ASCT was performed at the time of consolidation therapy (without radiation) in 7 patients, at first recurrence in 4 (including 1 without radiation), and at second recurrence in 1. Department of Neurosurgery and Neuro-Oncology (NSNO) was in charge from diagnosis to just before transplantation, Department of Hematopoietic Stem Cell Transplantation (HSCT) was in charge of HDC-ASCT, and Department of NSNO was in charge after discharge again. The conditioning regimen consisted of busulfan 3.2mg/kg/day for 4 days and thiotepa 5mg/kg/day for the 2 following days, followed by ASCT. The observation period after HDC-ASCT ranged from 2.8 to 43 months (median 16.1 months), and the hospitalization period for HDC-ASCT ranged from 26 to 38 days (median 33 days), with no serious complications. All patients have returned to society and there have been no deaths to date, but two patients (after 4.7 months and 10.9 months) had relapses, of which two were treated with tirabrutinib, and one was subsequently treated palliatively. HDC-ASCT in PCNSL is an important option to improve outcomes. Since the main focus of this treatment is Department of HSCT, it is important to have sufficient cooperation and communication among the departments from the time of tumor diagnosis until after the patient is discharged from transplantation, and it is essential to be fully aware of each role.
MET-5 OUTCOME OF MULTIDISCIPLINARY TREATMENT FOR BRAIN METASTASES IN PATIENTS WITH MELANOMA IN THE ERA OF MODERN SYSTEMIC THERAPY
Authors: Mitsuya Koichi , Deguchi Shoichi , Ito Shohei , Nakasu Yoko , Hayashi Nakamasa
Published: December 2022

Objective

Recently modern systemic therapy and stereotactic irradiation have been developed. We reviewed the therapeutic outcome of brain metastases (BM) in patients with melanoma.

Methods

Data of patients with melanoma BM were retrospectively analyzed. Patients underwent multidisciplinary treatment, whole brain radiotherapy, stereotactic irradiation, immune check point inhibitor (ICI) and/or BRAF inhibitor, therapeutic indication was discussed at cancer board. If they had 3cm over diameter, surgical resection for BM was performed, when systemic life expectancy longer than three months after control of their BM and controlled extra-CNS metastases. Radiotherapy of BM was selected with number, size and location. Overall survival was analysis with Kaplan-Meier survival curves.

Results

Eighty-four patients were treated melanoma BM between November 2004 and December 2021 at our institution. Median age was 61 years, and 54% male. Sixty-seven patients were treated BM, but 17 were selected best supportive care from progressive systemic disease. After radiotherapy, 18 patients were administrated ICI, and BRAF inhibitor 10, both ICI and BRAF inhibitor 5, cytotoxic chemotherapy 13. Median overall survival (mOS) of treatment group was 132 days (95%CI: 90-230) from the diagnosis of brain metastases, and 35 days for BSC. MOS in patients both local (radiotherapy and/or surgery for BM) and systemic therapy was longer than that of local alone (209, 64 days, p<0.0001). MOS of surgery group (n=10) was superior longer than the others (420, 92 days, p<0.0001). For treatment period, patients diagnosed BM after 2014 longer than that before 2013 (175, 117 days, p<0.0001), when ICI was started to use for melanoma in Japan.

Conclusion

Stereotactic irradiation and/or surgery supported with modern systemic therapy may be effective strategy in patients with melanoma BM. Further clinical investigations with larger cohort are needed to clarify appropriate assessments for patients with melanoma BM.
MET-9 LEPTOMENINGEAL CARCINOMATOSIS ~ ITS' ASSOCIATION WITH MOLECULAR AND PATHOLOGICAL SUBTYPES~
Authors: Iuchi Toshihiko , Hosono Junji , Setoguchi Taiki , Hasegawa Yuzo , Sakaida Tsukasa
Published: December 2022

Background

Leptomeningeal carcinomatosis (LMC) is the most difficult condition to treat brain metastases (BM), and the presence or absence of malignant cells in the cerebrospinal fluid (CSF) is important in determining treatment strategies. Here, we defined Type I LMC (CSF cytology positive) as LMC, and compared the risk of LMC in lung cancer (LC) by subtypes.

Patients and Methods

In principle, at our hospital, we confirm CSF cytology when any of the following is observed: enhanced lesion in contact with the cerebrospinal fluid cavity, cranial nerve symptoms, or concurrent hydrocephalus. Of the 833 cases of BM from LC diagnosed since 2005, 794 cases, excluding 39 cases for which molecular diagnosis was not performed, were enrolled.

Results

There existed EGFRm: 321 cases, ALK: 19 cases, without driver mutation (w/oDM): 313 cases, small cell lung cancer (SCLC): 141 cases. 1326 CSF cytological examinations were performed in 533 patients, and 162 were diagnosed as LMC. The frequency of LMC at diagnosis of BM was EGFRm: 8.7%, ALK: 5.3%, w/oDM: 3.2%, and SCLC: 0.0% (P<0.0001). The time to LMC from diagnosis of LC was significantly shorter in EGFRm than ALK (H.R.:4.89, P=0.027), w/oDM (H.R.:2.96, P<0.0001), and SCLC (H.R.:7.23, P<0.0001). The use of TKIs after diagnosis of LC in EGFRm patients did not prevent LMC (HR: 0.932, P=0.493). The time to LMC from diagnosis of BM was also shorter in EGFRm in compared with ALK (H.R.: 4.89, P=0.027), w/oDM (H.R.: 3.94, P=0.057), and SCLC (H.R.: 8.94, P<0.0001). L858R had a higher risk of LMC than Ex19deletion (HR: 1.59, P=0.037). Neither TKI use (HR: 0.989, P=0.971) nor radiotherapy (HR: 0.846, P=0.567) prevented LMC.

Conclusion

EGFRm has a higher risk of developing LMC than other subtypes, and it is thought to be a factor in the high risk of central nervous system death in this subtype.
BT-4 PROGNOSIS OF HISTOLOGICALLY DIAGNOSED GRADE 2-3 IDH-WILD TYPE DIFFUSE GLIOMAS TREATED WITH RADIATION AND TEMOZOLOMIDE
Authors: Arita Hideyuki , Takayangi Shunsaku , Tanaka Shota , Nakamura Taishi , Shirahata Mitsuaki , Tamura Kaoru , Uduka Takeo , Nagane Motoo , Narita Yoshitaka , Ichimura Koichi
Published: December 2022

Although adult diffuse gliomas, IDH-wildtype, histologically diagnosed as grade 2-3 have been regarded as clinically equivalents with glioblastomas, the prognosis of this population has scarcely been discussed with further consideration of treatment backgrounds. This retrospective study aimed to investigate the prognosis of adult patients with IDH-wildtype diffuse gliomas histologically diagnosed as WHO grade 2-3 using a cohort with homogenous treatment background. A total of 214 IDH-wildtype cases were extracted from the collected data of the previous study investigating the prognostic significance of molecular markers (Arita, Acta Neuropathol Commun 2016). The inclusion criteria were as follows: supratentorial tumor, pretreatment Karnofsky Performance status of 70 or higher, wildtype-H3.3 status, chemoradiation therapy with temozolomide after the initial surgery. Overall survival (OS) and progression free survival (PFS) were evaluated by Kaplan-Meier methods. The histological diagnosis in this study was made based on the WHO 2016 classification, and the histological criteria is compatible with the current classification (CNS WHO5).The mean age was 62.8, 59.8 and 60.2 years in grade 2 (n=8), 3 (n=45) and 4 (n=161) case, respectively. The higher ratio of biopsy cases was associated lower grades (50% in grade 2, 22% in grade 3 and 9% in grade 4 cases). Grade 2-3 cases showed short survival (OS 24.7 months and PFS 9.7months) despite the intensive treatment of chemoradiation at the time of diagnosis. In details, OS was 41.5, 23.1 and 17.8 months in grade 2, 3 and 4 cases, respectively. PFS was 12.6, 9.7 and 8.2 months in grade 2, 3 and 4 cases, respectively. Our results revealed that IDH-wildtype grade 2-3 cases showed dismal prognosis even after the chemoradiation at the time of diagnosis. Further development of treatments is needed in this population as well as glioblastomas, IDH-wildtype.
COT-1 EXPERIENCE OF THE BRAIN TUMORS DURING PREGNANCY AT OUR HOSPITAL
Authors: Mohri Genshin , Kitano Yotarou , Matsubara Toshio , Suzuki Hidenori
Published: December 2022

Treatment for symptomatic brain tumors is rare during pregnancy, and treatment strategies vary depending on the time of pregnancy. We report three cases of brain tumor under pregnancy at our institution. Case 1 was a 37-year-old woman at 6 weeks gestation and was transported by emergency due to status epileptics. Malignant glioma of the right frontal lobe was suspected by imaging. Diagnosis was Oligodendroglioma IDH mutant grade2. Case 2 was a 41-year-old woman diagnosed with von Hippel-Lindau disease, had a history of multiple surgeries, and was image-followed for new nodular lesions. She developed gait disturbance at 23 weeks gestation, and MRI showed cyst formation in the nodular lesion, and she was referred to our hospital. The treatment was to remove the tumor after cesarean section, and at 26 weeks gestation, simultaneous tumor removal after cesarean section was performed, and both mother and baby were in good condition. Case 3 was a 35-year-old woman who became aware of visual field abnormalities at 37 weeks gestation, and pointed out a pituitary tumor. She underwent endoscopic tumor resection one week after the caesarean section. In a 2008 paper, the algorithm of the treatment guideline for brain tumors associated with pregnancy is often treated in line. Basically, the priority is given to the mother, and the treatment policy differs depending on the time of pregnancy and the condition of the mother and fetus. It is necessary to collaborate with multiple departments such as obstetrics and gynecology, anesthesiology, and pediatrics, such as whether or not pregnancy can be continued and surgical treatment is required.
COT-18 DATABASE STUDY ON TRENDS IN MEDICAL EXAMINATIONS OF PATIENTS WITH MALIGNANT BRAIN TUMORS
Authors: Hirose Yuko , Fukui Daisuke , Sunahara Nanae , Narita Yoshitaka , Horibuchi Yuzo
Published: December 2022

Background and Purpose

Glioblastoma is the most is the poorest prognosis tumor of all carcinomas. Various factors contribute to deterioration for glioblastoma such as age, KPS, and surgical removal level. The most important factors for poor prognosis are that half of patients with glioblastoma have a KPS ≤ 70 at the start of treatment because glioblastoma progresses rapidly. There have been no comprehensive reports on the trends in visits and time to initiation of treatment for patients with glioblastoma. We analyzed the actual clinical course of malignant brain tumor patients using the receipt database with the aim of raising awareness of prompt diagnosis and treatment.

Methods

Because this study included patient-visit transitions, we utilized receipt data from JMDC Inc., which can be tracked through changes of medical facilities. We analyzed for data for the period January 1, 2005, to March 31, 2022.

Results and Discussion

The study included 493 patients with malignant neoplasms of brain, aged 18 years or older, who underwent surgery and received radiation or temozolomide. The medical departments that visited for the first time before surgery were general internal medicine, neurosurgery, followed by ophthalmologist, orthopedics, and otolaryngology. The period from the date of the first visit to surgery was 21 days for neurosurgery and 46 days for general internal medicine. The mean time from MRI to surgery was 11 days when surgery was performed at the MRI site, and 22 days when the patient was referred to another hospital after MRI. This study clarified the actual situation when patients with malignant brain tumors visit a department besides neurosurgery. In order to facilitate prompt diagnosis and treatment, it is necessary to raise awareness of the disease among the departments where patients are likely to visit for the first time.
Bio-syncretic robots composed of biological and electromechanical systems
Authors: Zhang Chuang , Yang Jia , Wang Wenxue , Liu Lianqing
Published: December 2022

Potential approaches to developing bio-syncretic robots are proposed in different dimensions, including monomial functions and closed loop systems of living cell-based sensing, intelligence, and actuation.
Pervasive hybridization during evolutionary radiation ofRhododendronsubgenusHymenanthesin mountains of southwest China
Authors: Ma Yazhen , Mao Xingxing , Wang Ji , Zhang Lei , Jiang Yuanzhong , Geng Yuying , Ma Tao , Cai Liming , Huang Shuangquan , Hollingsworth Pete , Mao Kangshan , Kang Minghui , Li Yiling , Yang Wenlu , Wu Haolin , Chen Yang , Davis Charles C , Shrestha Nawal , Ree Richard H , Xi Zhenxiang , Hu Quanjun , Milne Richard I , Liu Jianquan
Published: December 2022

Radiations are especially important for generating species biodiversity in mountainous ecosystems. The contribution of hybridization to such radiations has rarely been examined. Here, we use extensive genomic data to test whether hybridization was involved in evolutionary radiation within Rhododendron subgenus Hymenanthes, whose members show strong geographic isolation in the mountains of southwest China. We sequenced genomes for 143 species of this subgenus and 93 species of four other subgenera, and found that Hymenanthes was monophyletic and radiated during the late Oligocene to middle Miocene. Widespread hybridization events were inferred within and between the identified clades and subclades. This suggests that hybridization occurred both early and late during diversification of subgenus Hymenanthes, although the extent to which hybridization, speciation through mixing-isolation-mixing or hybrid speciation, accelerated the diversification needs further exploration. Cycles of isolation and contact in such and other montane ecosystems may have together promoted species radiation through hybridization between diverging populations and species. Similar radiation processes may apply to other montane floras in this region and elsewhere.
E-cigarette Use Patterns, Flavors, and Device Characteristics Associated With Quitting Smoking Among a U.S. sample of Adults Using E-cigarettes in a Smoking Cessation Attempt
Authors: Bold Krysten , O’Malley Stephanie , Krishnan-Sarin Suchitra , Morean Meghan
Published: December 2022

Introduction

Many adults who smoke cigarettes use e-cigarettes to try to quit smoking; however, some are not successful. Identifying factors that are associated with successfully quitting smoking using e-cigarettes is important for maximizing cigarette cessation.

Aims and Methods

Online survey data were collected in 2021 from 857 adults in the United States who reported using e-cigarettes in a recent attempt to quit smoking. Survey items assessed patterns of e-cigarette use and device characteristics (flavors, device, and nicotine) used when trying to quit smoking. Multivariable linear regression models examined characteristics associated with the longest duration of smoking abstinence when using e-cigarettes to try to quit.

Results

The average duration of smoking abstinence when using e-cigarettes during a quit attempt was 65 days (SD = 104). In the multivariable model, greater frequency of e-cigarette use when quitting and abruptly switching to e-cigarettes from cigarettes (vs. gradually reducing) were significantly associated with longer durations of abstinence (p < .001). Preference for non-tobacco (relative to tobacco) flavors and nicotine concentration were not associated with duration of abstinence, although preference for rechargeable pod and mod device types (vs. cig-a-likes) was associated with longer durations of abstinence.

Conclusions

Patterns of e-cigarette use were related to abstinence duration, which may provide guidance for adults who are using e-cigarettes to quit smoking to encourage complete substitution and maximize smoking cessation. Findings indicate that non-tobacco e-cigarette flavors and nicotine strength are not related to longer durations of cessation success for adults, which may inform tobacco regulatory policies limiting these constituents to protect public health.

Implications

This study provides important new information about the characteristics of e-cigarettes used during an attempt to quit smoking among adults across the United States and identifies factors associated with quitting success. Patterns of e-cigarette use were associated with longer durations of abstinence. In contrast, few e-cigarette characteristics were associated with abstinence. Although preference for some pod and mod device types was associated with longer abstinence duration compared to earlier cig-a-like devices, preference for non-tobacco (vs. tobacco) flavor and nicotine concentration were not associated with abstinence. Findings may help inform guidance for adults using e-cigarettes to quit smoking and support tobacco regulatory policies.
Ascorbate peroxidase 1 allows monitoring of cytosolic accumulation of effector-triggered reactive oxygen species using a luminol-based assay
Authors: Hong Xiufang , Qi Fan , Wang Ran , Jia Zhiyi , Lin Fucheng , Yuan Minhang , Xin Xiu-Fang , Liang Yan
Published: December 2022

Biphasic production of reactive oxygen species (ROS) has been observed in plants treated with avirulent bacterial strains. The first transient peak corresponds to pattern-triggered immunity (PTI)-ROS, whereas the second long-lasting peak corresponds to effector-triggered immunity (ETI)-ROS. PTI-ROS are produced in the apoplast by plasma membrane-localized NADPH oxidases, and the recognition of an avirulent effector increases the PTI-ROS regulatory module, leading to ETI-ROS accumulation in the apoplast. However, how apoplastic ETI-ROS signaling is relayed to the cytosol is still unknown. Here, we found that in the absence of cytosolic ascorbate peroxidase 1 (APX1), the second phase of ETI-ROS accumulation was undetectable in Arabidopsis (Arabidopsis thaliana) using luminol-based assays. In addition to being a scavenger of cytosolic H2O2, we discovered that APX1 served as a catalyst in this chemiluminescence ROS assay by employing luminol as an electron donor. A horseradish peroxidase (HRP)-mimicking APX1 mutation (APX1W41F) further enhanced its catalytic activity toward luminol, whereas an HRP-dead APX1 mutation (APX1R38H) reduced its luminol oxidation activity. The cytosolic localization of APX1 implies that ETI-ROS might accumulate in the cytosol. When ROS were detected using a fluorescent dye, green fluorescence was observed in the cytosol 6 h after infiltration with an avirulent bacterial strain. Collectively, these results indicate that ETI-ROS eventually accumulate in the cytosol, and cytosolic APX1 catalyzes luminol oxidation and allows monitoring of the kinetics of ETI-ROS in the cytosol. Our study provides important insights into the spatial dynamics of ROS accumulation in plant immunity.
ThePhytophthora sojaeeffector PsFYVE1 modulates immunity-related gene expression by targeting host RZ-1A protein
Authors: Lu Xinyu , Yang Zitong , Song Wen , Miao Jinlu , Zhao Hanqing , Ji Peiyun , Li Tianli , Si Jierui , Yin Zhiyuan , Jing Maofeng , Shen Danyu , Dou Daolong
Published: December 2022

Oomycete pathogens secrete numerous effectors to manipulate plant immunity and promote infection. However, relatively few effector types have been well characterized. In this study, members of an FYVE domain-containing protein family that are highly expanded in oomycetes were systematically identified, and one secreted protein, PsFYVE1, was selected for further study. PsFYVE1 enhanced Phytophthora capsici infection in Nicotiana benthamiana and was necessary for Phytophthora sojae virulence. The FYVE domain of PsFYVE1 had PI3P-binding activity that depended on four conserved amino acid residues. Furthermore, PsFYVE1 targeted RNA-binding proteins RZ-1A/1B/1C in N. benthamiana and soybean (Glycine max), and silencing of NbRZ-1A/1B/1C genes attenuated plant immunity. NbRZ-1A was associated with the spliceosome complex that included three important components, glycine-rich RNA-binding protein 7 (NbGRP7), glycine-rich RNA-binding protein 8 (NbGRP8), and a specific component of the U1 small nuclear ribonucleoprotein complex (NbU1–70K). Notably, PsFYVE1 disrupted NbRZ-1A–NbGRP7 interaction. RNA-seq and subsequent experimental analysis demonstrated that PsFYVE1 and NbRZ-1A not only modulated pre-mRNA alternative splicing (AS) of the necrotic spotted lesions 1 (NbNSL1) gene, but also co-regulated transcription of hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (NbHCT), ethylene insensitive 2 (NbEIN2), and sucrose synthase 4 (NbSUS4) genes, which participate in plant immunity. Collectively, these findings indicate that the FYVE domain-containing protein family includes potential uncharacterized effector types and also highlight that plant pathogen effectors can regulate plant immunity-related genes at both AS and transcription levels to promote disease.
Human threat learning is associated with gut microbiota composition
Authors: Oyarzun Javiera P , Kuntz Thomas M , Stussi Yoann , Karaman Olivia T , Vranos Sophia , Callaghan Bridget L , Huttenhower Curtis , LeDoux Joseph E , Phelps Elizabeth A
Published: December 2022

The ability to learn about threat and safety is critical for survival. Studies in rodent models have shown that the gut microbiota can modulate such behaviors. In humans, evidence showing an association with threat or extinction learning is lacking. Here, we tested whether individual variability in threat and extinction learning was related to gut microbiota composition in healthy adults. We found that threat, but not extinction learning, varies with individuals’ microbiome composition. Our results provide evidence that the gut microbiota is associated with excitatory threat learning across species.
Balancing novelty and appropriateness leads to creative associations in children
Authors: Rastelli Clara , Greco Antonino , De Pisapia Nicola , Finocchiaro Chiara
Published: December 2022

Creative problem solving is a fundamental skill of human cognition and is conceived as a search process whereby a novel and appropriate solution is generated. However, it is unclear whether children are able to balance novelty and appropriateness to generate creative solutions and what are the underlying computational mechanisms. Here, we asked children, ranging from 10 to 11 years old, to perform a word association task according to three instructions, which triggered a more appropriate (ordinary), novel (random), or balanced (creative) response. Results revealed that children exhibited greater cognitive flexibility in the creative condition compared to the control conditions, as revealed by the structure and resiliency of the semantic networks. Moreover, responses’ word embeddings extracted from pretrained deep neural networks showed that semantic distance and category switching index increased in the creative condition with respect to the ordinary condition and decreased compared to the random condition. Critically, we showed how children efficiently solved the exploration/exploitation trade-off to generate creative associations by fitting a computational reinforcement learning (RL) model that simulates semantic search strategies. Our findings provide compelling evidence that children balance novelty and appropriateness to generate creative associations by optimally regulating the level of exploration in the semantic search. This corroborates previous findings on the adult population and highlights the crucial contribution of both components to the overall creative process. In conclusion, these results shed light on the connections between theoretical concepts such as bottom-up/top-down modes of thinking in creativity research and the exploration/exploitation trade-off in human RL research.
Membrane-domain mutations in respiratory complex I impede catalysis but do not uncouple proton pumping from ubiquinone reduction
Authors: Jarman Owen D , Hirst Judy
Published: December 2022

Respiratory complex I [NADH:ubiquinone (UQ) oxidoreductase] captures the free energy released from NADH oxidation and UQ reduction to pump four protons across an energy-transducing membrane and power ATP synthesis. Mechanisms for long-range energy coupling in complex I have been proposed from structural data but not yet evaluated by robust biophysical and biochemical analyses. Here, we use the powerful bacterial model system Paracoccus denitrificans to investigate 14 mutations of key residues in the membrane-domain Nqo13/ND4 subunit, defining the rates and reversibility of catalysis and the number of protons pumped per NADH oxidized. We reveal new insights into the roles of highly conserved charged residues in lateral energy transduction, confirm the purely structural role of the Nqo12/ND5 transverse helix, and evaluate a proposed hydrated channel for proton uptake. Importantly, even when catalysis is compromised the enzyme remains strictly coupled (four protons are pumped per NADH oxidized), providing no evidence for escape cycles that circumvent blocked proton-pumping steps.
Basic kirwan injectivity and its applications
Authors: Lin Yi , Yang Xiangdong
Published: December 2022

Consider the Hamiltonian action of a torus on a transversely symplectic foliation that is also Riemannian. When the transverse hard Lefschetz property is satisfied, we establish a foliated version of the Kirwan injectivity theorem and use it to study Hamiltonian torus actions on transversely Kähler foliations. Among other things, we prove a foliated analogue of the Carrell–Liberman theorem. As an application, this confirms a conjecture raised by Battaglia–Zaffran on the basic Hodge numbers of symplectic toric quasifolds. Our methods also allow us to present a symplectic approach to the calculation of the basic Betti numbers of symplectic toric quasifolds.
Social status and the consumption of highly processed foods in Nigeria
Authors: Mekonnen Daniel A , Achterbosch Thom , Ruben Ruerd
Published: December 2022

Food has been used to define social classes and as a means of embodying the ‘good life’. Depending on the food culture and food environment, certain foods may be consumed more by the relatively higher income groups and therefore are perceived as ‘positional’. This study examines whether social status—proxied by the relative consumption expenditures (the rank in the consumption expenditure distribution) and the relative deprivation in consumption expenditures—can explain household food choices. Based on the nationally representative Nigeria General Household Panel Surveys and using fixed effects estimations, we find that consumption of highly processed foods is strongly associated with the social status of the household. We observe differences among highly processed foods consumed at home and away from home, across geographic locations and consumption expenditure terciles. The results of this study provide suggestive evidence that reducing income inequality is required to support healthier household food preferences beyond social status.
Craniofacial phenotyping by photogrammetry in Chinese prepubertal children with obstructive sleep apnea
Authors: Yuen Hoi Man , Chan Kate Ching-ching , Chu Winnie Chiu Wing , Chan Joey W Y , Wing Yun Kwok , Li Albert Martin , Au Chun Ting
Published: December 2022

Study Objectives

This study aimed to examine the craniofacial phenotype of Chinese prepubertal children with and without obstructive sleep apnea (OSA) using a quantitative photographic analysis technique and to develop a prediction model for OSA diagnosis based on the photogrammetric data. Potential ethnic differences in the association between OSA and photogrammetric data between Chinese and Caucasian children were also examined.

Methods

This was a cross-sectional study. Chinese children aged 5–12 years old, suspected to have OSA were recruited from our sleep clinic. Frontal and side photos were taken for craniofacial phenotyping by photogrammetry. Polysomnography was performed and participants were divided into three groups: non-OSA (obstructive apnea hypopnea index (OAHI) < 1/h), mild OSA (OAHI between 1/h and 5/h), and moderate-to-severe (MS) OSA (OAHI ≥ 5/h). Prediction models were built from 70% of training data using logistic regression and evaluated on the remaining 30% of test data for receiver operating characteristic (ROC) curve construction.

Results

This study included 90 participants (mean age: 8.2 ± 1.6 years, 67 males). Non-OSA, mild OSA, and MS OSA groups included 32, 31, and 27 participants, respectively. There were significant trends for an increasing maxillary-mandibular relationship angle (p = .002) and a decreasing anterior mandibular height to whole face length ratio (p < .001) with increasing OSA severity. A prediction model built with clinical measurements and the two photogrammetric features yielded an area under the ROC curve (AUC) of 0.81 (95% C.I.: 0.64–0.96).

Conclusions

Craniofacial features obtained by photogrammetry are significantly different between OSA groups in prepubertal children. Increased maxillary-mandibular relationship angle is an OSA feature found in both Asian and Caucasian children.
Increased connectivity of the anterior cingulate cortex is associated with the tendency to awakening during N2 sleep in patients with insomnia disorder
Authors: Guo Yupeng , Zou Guangyuan , Shao Yan , Chen Jie , Li Yuezhen , Liu Jiayi , Yao Ping , Zhou Shuqin , Xu Jing , Hu Sifan , Gao Jia-Hong , Zou Qihong , Sun Hongqiang
Published: December 2022

Study Objectives

To investigate the relationship between sleep transition dynamics and stage-specific functional connectivity (FC) of the anterior cingulate cortex (ACC) in patients with insomnia disorder (ID).

Methods

Simultaneous electroencephalography–functional magnetic resonance imaging (EEG–fMRI) data from 37 patients with ID and 30 well-matched healthy controls (HCs) were recorded during wakefulness and different sleep stages and subsequently analyzed. A Markov chain model was used to estimate the transition probability between each stage. The FC between the ACC (set as the seed) and voxels across the whole brain was calculated. A linear mixed effect model was used to determine the group-by-stage interaction of the seed-based connectivity. The correlation between the sleep-stage transition probability and the ACC-based connectivity was explored.

Results

Patients with ID exhibited a higher likelihood of transitioning from N2 to wakefulness than HCs. A significant group-by-stage interaction of connectivity with the bilateral ACC was observed in the cerebellar, subcortical, and cortical regions. Moreover, a significant positive correlation was found in patients with ID between the transition probability from N2 to wakefulness and the FC of the ACC with the anterior cerebellum in N2 (r = 0.48).

Conclusions

This exploratory analysis indicates that enhanced FC between the ACC and cerebellum represents a potential neural pathway underlying the greater likelihood of patients with ID waking during N2 sleep. These findings contribute to an emerging framework that reveals the link between sleep maintenance difficulty and ACC function, further highlighting the possibility that N2 sleep is a therapeutic target for meaningfully reducing sleep disruption.
Prevalence of frequent nightmares and their prospective associations with 1-year psychiatric symptoms and disorders and functioning in young adults: a large-scale epidemiological study in Hong Kong
Authors: Wong Stephanie M Y , Hui Christy L M , Cheung Vivian K W , Suen Yi Nam , Chan Sherry K W , Lee Edwin H M , Chan Kai Tai , Wong Michael T H , Chen Eric Y H
Published: December 2022

Study Objectives

No study has yet examined the prevalence of frequent nightmares in representative youth populations in Asia and how they may contribute to future mental health risks. We aimed to fill this gap using data from a large-scale household-based youth sample in Hong Kong.

Methods

Participants were consecutively recruited from a large-scale epidemiological youth mental health study in Hong Kong (n = 3132). A subset of participants were invited for a follow-up assessment after 1 year (n = 1154 in the final analyses). Frequent nightmares (≥1/week during the past month) were assessed using an item from the Pittsburgh Sleep Quality Index. Univariate analyses and multivariable logistic regression models were applied to examine the contribution of frequent nightmares at baseline to moderate-to-severe depressive and anxiety symptoms, post-traumatic stress disorder symptoms, and 30-day major depressive episode (MDE) or generalized anxiety disorder (GAD), both at baseline and follow-up. The long-term functional implications of frequent nightmares were also examined.

Results

The prevalence of frequent nightmares was 16.3%. Females were more likely to experience frequent nightmares (20.4%) compared to males (12.1%), p < 0.001. Baseline frequent nightmares were significantly associated with all four mental health outcomes at 1 year. Notably, their prospective associations with depressive and anxiety symptoms and 30-day MDE/GAD remained significant even after adjusting for external stressors, resilience, and sociodemographic characteristics. Frequent nightmares were also significantly associated with both current and 1-year functional impairments.

Conclusions

Frequent nightmares have significant long-term implications on mental health and functioning. Identifying young adults with frequent nightmares can improve early risk detection and intervention in the population.
Stochastic, individual animal systems simulation model of beef cow–calf production: development and validation
Authors: Aherin Dustin G , Weaber Robert L , Pendell Dustin L , Heier Stamm Jessica L , Larson Robert L
Published: December 2022

A stochastic, individual animal systems simulation model describing U.S. beef cow–calf production was developed and parameterized to match typical U.S. Angus genetics under cow–calf production conditions in the Kansas Flint Hills. Model simulation results were compared to available actual, multivariate U.S. cow–calf production data reported according to beef cow–calf standardized performance analysis (SPA) methodology through North Dakota State University’s CHAPS program to assess model validity. Individual animal nutrition, reproduction, growth, and health characteristics, as well as production state are determined on a daily time step. Any number of days can be simulated. These capabilities allow for decision analysis and assessment of long-run outcomes of various genetic, management, and economic scenarios regarding multiple metrics simultaneously. Parameterizing the model to match Kansas Flint Hills production conditions for the years 1995 through 2018, 32 different genetic combinations for mature cow weight and peak lactation potential were simulated with 100 iterations each. Sire mature cow weight genetics ranged from 454 to 771 kg in 45 to 46 kg increments. Sire peak lactation genetics were considered at 6.8, 9, 11.3, and 13.6 kg/d for all eight mature cow weights. Utilizing model results for the years 2000 to 2018, raw model results were assessed against actual historical cow–calf production data. Exploratory factor analysis was applied to interpret the underlying factor scores of model output relative to actual cow–calf production data. Comparing modeled herd output with CHAPS herd data, median average calf weaning age, average cow age, percent pregnant per cow exposed, and percent calf mortality per calf born of model output was 3.4 d greater, 0.2 yr greater, 1 percentage point less, and 1.7 percentage points greater, respectively. Subtracting the median CHAPS pre-weaning average daily gain from the median modeled pre-weaning average daily gain for each of the eight respective mature cow weight genetics categories, and then calculating the median of the eight values, the median difference was −0.21 kg/d. Performing the same calculation for birth weight and adjusted 205 d weaning weight, the modeled data was 4.9 and 48.6 kg lighter than the CHAPS data, respectively. Management and genetic details underlying the CHAPS data were unknown.
Effect of a multicarbohydrase containing α-galactosidase in sow lactating diets with varying energy density
Authors: Llamas-Moya Sara , Duong Tri , Petersen Grant I , Bertram Mark J , Kitt Steve J
Published: December 2022

Sow productivity improvements are associated with high energetic demand due to increasing prolificity. The reproductive life and longevity of sows, and the readiness for weaning of the offspring may be impaired when sows loose significant body weight (BW) during lactation. The impact of a multicarbohydrase containing α-galactosidase on a low energy dense lactation diet was evaluated in this study. Two-hundred and eight sows (208 ± 25.2 kg) were blocked by parity and BW to one of four treatments, in which a corn-soybean meal diet was formulated to have varying levels of added fat (0, 1.5%, and 3%) to titrate an energy density model. A fourth treatment replicated the 0% added fat formulation with enzyme supplementation at 250 g/tonne. Sows were weighed individually on entry, post-farrow (by calculation) and at weaning. Daily feed intakes (ADFI) and caloric intake were used for calculation of sow feed efficiency (FE) and caloric efficiency. Litter performance was characterized at birth, and size was standardized within 24h of farrow and within treatment to ensure uniform litter sizes. Average wean weight and pre-weaning mortality were determined. Piglets were weighted individually to study litter weight distribution. Data was analyzed as a randomized completely block design, using sow as the experimental unit, treatment as the main effect, and standardized average weight and litter sizes as covariates where appropriate. Although sows fed a multicarbohydrase had lower standardized litter size (P < 0.001), average wean weight was higher in this group and equivalent to the 3% added fat treatment. Enzyme supplementation tended to reduce the proportion of light weight pigs (BW < 4.1kg) within the litter, when compared with the 0% added fat diet (P < 0.1). The multicarbohydrase tended to increased sow ADFI (P < 0.10), although sows from all treatments had equivalent caloric intakes during lactation (P > 0.1). Enzyme supplementation yielded significant improvements in sow FE (P < 0.01), similar to the 3% added fat group. Thus, the carbohydrase degrading enzyme tested in this study improved the efficiency of sows, while increasing average wean weights of the offspring, suggesting an improvement in nutrient digestion and/or metabolic efficiency from typical lactation diets.
Unsteady slipstream of a train passing through a high-speed railway tunnel with a cave
Authors: Xiong Xiaohui , Cong Rilong , Li Xiaobai , Geng Yutang , Tang Mingzan , Zhou Shujun , Na Yanling , Jiang Chongxu
Published: December 2022

The cave is of great importance for the storage of equipment and to avoid having workers in the tunnel, but it changes the tunnel section, leads to a change of slipstream and affects the safety of trains and workers. The Re-normalization group (RNG) k-ε turbulence method is used to investigate the slipstream induced by a single train passing through a double-track tunnel at 350 km/h. The slipstream in a tunnel with and without a cave is compared. The slipstream components in three directions are reported comprehensively. The results show that the existence of a cave changes the slipstream at the tail of the train. At measurement points before and after the train passes the cave, the intensity of the slipstream at the tail is mitigated; as the train passes the cave, the tail slipstream is enhanced to a certain extent. With increasing lateral distance, the peak value of the slipstream with a cave decreases faster than that without a cave. These findings suggest that the presence of a cave mitigates the slipstream intensity, but special attention should be paid to the design of ancillary facilities, especially their relative location.
Neither slugs nor snails: a molecular reappraisal of the gastropod family Velutinidae
Authors: Fassio Giulia , Stefani Matteo , Russini Valeria , Buge Barbara , Bouchet Philippe , Treneman Nancy , Malaquias Manuel António E , Schiaparelli Stefano , Modica Maria Vittoria , Oliverio Marco
Published: December 2022

The systematics of the marine mollusc family Velutinidae has long been neglected by taxonomists, mainly because their often internal and fragile shells offer no morphological characters. Velutinids are usually undersampled owing to their cryptic mantle coloration on the solitary, social or colonial ascidians on which they feed and lay eggs. In this study, we address the worldwide diversity and phylogeny of Velutinidae based on the largest molecular dataset (313 specimens) to date, accounting for > 50% of the currently accepted genera, coupled with morphological and ecological data. Velutinids emerge as a diverse group, encompassing four independent subfamily-level lineages, two of which are newly described herein: Marseniopsinae subfam. nov. and Hainotinae subfam. nov. High diversity was found at genus and species levels, with two newly described genera (Variolipallium gen. nov. and Pacifica gen. nov.) and ≥ 86 species in the assayed dataset, 58 of which are new to science (67%). Velutinidae show a remarkable morphological plasticity in shell morphology, mantle extension and chromatic patterns. This variability is likely to be the result of different selective forces, including habitat, depth and trophic interactions.
The Combination of TIM3-Based Checkpoint Blockade and Oncolytic Virotherapy Regresses Established Solid Tumors
Authors: Gowan Cody C. , Bartee Mee Y. , Flores Erica , Aksoy Bulent A. , Templeton Conor , Baillie Kati , Happe Myroslawa , Bartee Eric
Published: December 2022

T-cell immunoglobulin and mucin domain 3 (TIM3) is emerging as a potential target for antibody-based checkpoint blockade. However, the efficacy of TIM3 blockade in combination with other treatment modalities, has not been extensively studied. In the current work we combined TIM3 blockade with myxoma virus-based oncolytic virotherapy (OV). Our results demonstrate that myxoma virus’s ability to initiate an immense antitumor immune response complements the ability of TIM3 blockade to shift the tumor microenvironment to a more proinflammatory state. As a result, the combination of TIM3 blockade and OV is able to completely eradicate established disease, while neither monotherapy is effective. These data represent the first demonstration that OV can enhance the efficacy of TIM3 blockade and suggest that this treatment may need to be incorporated into more aggressive, combinatorial regimens in order to fulfill its potential as an immunotherapeutic.