bluuebunny/crossref_metadata_2025 huggingface dataset:
P17.08.B Single institutional retrospective review of re-irradiation in High Grade Gliomas in a tertiary UK centre
Authors: Manik V , Brazil L , Swampillai A , Chia K , Al-Salihi O
Published: September 2022

Background

Recurrent high grade gliomas (HGG) pose a treatment challenge as no definite guidelines exist. Re-excision could be appropriate in some cases while systemic therapy options are only a handful. We thus need to resort to the option of re-irradiation at some point but there could be a wide variety of techniques, volumes & doses to choose from due to lack of robust evidence. The UK wide BRIOCHe study for Glioblastoma Multiforme (GBM) will help in providing some standardisation. With this retrospective study, we aim to review our institutional practice with re-irradiation & our patient outcomes.

Material and Methods

Electronic health records over a period of 3 years from 1 Jun 2019 to 30 May 2021 were searched for patients with HGG that underwent a course of re-irradiation. Various patient factors, tumour & treatment factors at baseline and at recurrence and survival data were collected.

Results

Total of 8 patients received re-irradiation with all except one having a performance status of 1 at the time of treatment. Seven patients had GBM, one had transformation from baseline G2 glioma and the eighth patient had anaplastic oligodendroglioma (ODG). MGMT was methylated in 62.5% patients while IDH mutation was present only in the transformed glioma. Majority patients had radiotherapy dose of 60Gy/30 fractions with concurrent temozolomide (TMZ) at baseline to a median CTV volume of 186cc. A median of 6 cycles of TMZ were given in the adjuvant setting. Median time to recurrence from completion of adjuvant treatment was 6.7 months (range: 0.9 - 171.6 months). Most recurrences were in the same or an adjacent lobe whereas 1 patient had a multi-focal recurrence. Half the patients at recurrence underwent a re-resection. All patients had salvage chemotherapy at the time of recurrence with a median of 2 regimens and a median of 6 cycles prior to re-irradiation. All patients received a re-irradiation dose of 35Gy in 10 fractions to a median CTV volume of 149cc. The median interval from previous radiotherapy was 18.9 months (range: 11.6 - 190.5 months). The median time to progression from re-RT was 5.4 months (CI: 3.4 - 7.4) and median survival from re-RT was 7 months (CI: 6.2 - 7.8). The median overall survival since diagnosis was 35.1 months (CI: 22.2 - 48.1), one patient was lost to follow up.

Conclusion

Re-irradiation is a safe & feasible treatment option in carefully selected cases of high grade glioma.
P17.10.B Identification of mechanisms involved in the recurrence of glioblastoma by transcriptomic, proteomic and spatial profiling analysis
Authors: Ritz M , Shekarian T , Martins T , Hogan S , Schmassmann P , Burger B , Hutter G
Published: September 2022

Background

Glioblastoma (GBM) is the most aggressive and common brain tumor. Despite multimodal therapy which consists of complete tumor removal, chemo- and radiation therapy in most patients, the tumor recurs, and the overall survival of only 14 months remains very poor. To identify tumor-induced immune evasion and treatment resistance mechanisms induced during GBM recurrence, we aimed at characterizing the immunological/molecular changes in patient-matched treatment-naïve and recurrent GBM samples.

Material and Methods

Proteins and total RNA were extracted from 16 patient-matched treatment-naïve (primary) and recurrent GBM fresh frozen tumor samples. The expression of genes involved in brain immune responses were compared using Nanostring panels encompassing Cancer and Neuroinflammation genes. Proteomic was conducted using 6 patient-matched primary and recurrent tumor samples. Immunostaining was performed on a tissue microarray containing matched primary and recurrent tumor samples to identify tumor cells and microglia in order to assess spatial transcriptome of these specific cell types in situ using GeoMX technology. Moreover, correlation analysis of differentially genes and proteins with time to relapse was performed.

Results

Genes significantly differentially expressed between primary and recurrent tumors revealed genes overexpressed in recurrent tumors belonging to “FCGR-mediated Phagocytosis” and “synapse pruning” pathways. Proteomic confirmed the synaptic signalling considering overexpressed proteins. Correlation studies with the time to relapse indicated that higher expression of FCG receptors, complement molecules and synaptic components correlate with shorter time to relapse, sharing similarities with neurodegenerative/cognitive disorders such as schizophrenia and Alzheimer disease. The source for these molecules is under evaluation with the spatial transcriptomic analysis.

Conclusion

Upregulation of specific proteins such as FCG receptors, complement and synaptic components may result in more favourable conditions for tumor regrowth and may therefore be identified as negative predictors patient outcome. Interfering with these molecules may represent novel therapeutic options after initial GBM surgery.
P17.13.A Verteporfin inhibits autophagy in glioblastoma cell lines
Authors: Casati G , Giunti L , Iorio A , Marturano A , Sardi I
Published: September 2022

Background

Glioblastoma (GBM) is the most common primary brain tumor with a poor prognosis, characterized by a high cellular heterogeneity and invasiveness. Multi-drug resistance (MDR), the blood brain barrier (BEE) and DNA repair systems let the survival of tumor cells, making the treatment with chemo and radiotherapy not effective. Autophagy is a physiological mechanism that allows the recycling of damaged proteins and organelles, in order to protect the correct cell turnover. However, in GBM this process promotes survival and proliferation in stressful conditions such as after a chemo and / or radiotherapy treatment. The Hippo pathway is an extremely important molecular signaling because it is involved in various tumorigenesis processes, for instance the epithelium-mesenchymal transition (EMT), in the increase of stemness, mechanotransduction and chemoresistance.

Material and Methods

The modulation of autophagy was evaluated in GBM cell lines (U87MG, T98G and A172) exploiting a fluorescent detection that allowed the quantification of the autophagosomal activity present into the cell lines. The rate of autophagy was assessed after the cell lines pharmacological treatment with Hippo pathway inhibitors, Verteporfin 2uM (VP) for 24h, Latrunculin 0,5uM (LAT) for 3h and Cytochalasin 1uM (CIT) for 3h, with Doxorubicin 0,5uM (DOX) for 24h and with the drugs combination (DOX-VP, DOX-LAT and DOX-CIT). Moreover, the expression of the autophagy marker LC3II / I was evaluated in all three GBM cell lines by Western Blotting (WB) experiments. To perform this technique, the cells were treated with DOX and Hippo pathway inhibitors respecting the pharmacological treatment previously used. Then, the proteins were extracted, quantified and finally the WB was performed.

Results

The results obtained showed that the three GBM cell lines without any drugs were marked by high levels of autophagy, similar to the cells treated with Rapamycin, an autophagy inducer. Moreover, the autophagy rate was definitely reduced after treatment with VP and DOX-VP in all three cell lines, including the chemoresistant T98G. Conversely, the other two Hippo pathway inhibitors (LAT-CIT) and DOX did not significantly change the rate of autophagy. The expression of LC3II / I was particularly low after treatment with VP and DOX-VP in all three cell lines while the other two inhibitors did not significantly change its expression.

Conclusion

In conclusion, these data demonstrated that the three GBM cell lines (U87MG, T98G and A172) are characterized by high levels of autophagy and the inhibition of the Hippo pathway with VP and especially the combination DOX-VP reduced the activation of this protumoral molecular mechanism in GBM cell lines.
P17.15.A Neoadjuvant immunotherapy in the treatment of recurrent glioblastoma: an overview of last decade
Authors: Nogueira B V , Cyntia Fonseca Lima Rodrigues A , Almeida I M
Published: September 2022

Background

Recurrent glioblastoma (ArGB) is one of the most common primary malignant brain tumors in adults, with a poor prognosis, with low patient survival even after treatment. Because of this, several studies were carried out evaluating different therapies for the treatment of ArGB, more recently studies have emerged regarding the use of neoadjuvant immunotherapy and its possible advantages in the treatment of such patients. Therefore, the present study aims to analyze the efficacy of neoadjuvant immunotherapy and its effect on the survival of patients with recurrent glioblastoma.

Material and Methods

A search was performed in PubMed, Embase and Cochrane databases using the keywords: “Immunotherapy, “neoadjuvant” and "recurrent glioblastoma". Articles from the last 10 years were selected and those that did not meet the inclusion criteria were excluded from the research, totaling 7 selected articles.

Results

Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy after surgery, had significantly prolonged survival compared to patients who were randomized to receive adjuvant post-surgical PD-1 blockade alone. Neoadjuvant PD-1 blockade was associated with up-regulation of T cells and interferon-γ-related gene expression, but with down-regulation of cell cycle-related gene expression within the tumor, which was not observed in patients receiving adjuvant therapy. isolated.

Conclusion

Neoadjuvant immunotherapy, through a PD-1 inhibitor, in patients with ArGB, results in positive biological effects, in addition to the clinical benefit of, on average, increasing overall survival considerably due in large part to the improvement of the immune response , with no noticeable adverse effects, thus being advantageous, although these results are early and the current studies are not very comprehensive. Larger studies are needed for greater reliability and statistical relevance.
P18.01.A The applicability of established clinical and histopathological risk factors for tumor recurrence during long-term perioperative care in meningioma patients
Authors: Lüthge S , Steinbicker A , Schipmann S , Streckert E M S , Hess K , Grauer O , Paulus W , Stummer W , Brokinkel B , Spille D C
Published: September 2022

Background

Risk factors for the prediction of late-onset tumor recurrence in meningioma patients are sparse but needed to estimate duration and control intervals during long-term follow-up in meningioma patients. In this study, we therefore analyzed the value of established risk factors for postoperative meningioma recurrence for the prediction of long-term prognosis in a large, single-center series.

Material and methods

Correlations of established clinical (age, sex, tumor location, extent of resection), radiological (postoperative tumor volume) and histopathological variables (WHO grade, brain invasion) with tumor relapse were analyzed separately after 3, 5, and 10 years following microsurgery for primary diagnosed intracranial meningioma between 1991 and 2021 in uni- and multivariate analyses. The prognostic value was compared to findings in the entire cohort.

Results

Within a median follow-up of 29 months (range: 0-307 months), recurrence was observed in 141 patients (12%) after a median PFS of 36 months. PFS among the entire cohort (n=1218) at 3, 5, 10 and 15 years postoperatively were 90%, 84%, 74% and 70%, respectively. Among all patients included, skull base location (HR: 1.51, 95%CI 1.05-2.16; p=.026), Simpson ≥IV resections (HR: 2.41, 95%CI 1.52-3.84; p<.001), high-grade histology (HR: 3.70, 95%CI 2.50-5.47; p<.001) and male gender (HR: 1.46, 95%CI 1.01-2.11; p=.042) were independent risk factors for recurrence. Skull base location (HR: 1.92, 95%CI 1.17-3.17; p=.010 and HR: 2.02, 95%CI 1.04-3.95; p=.038) and high-grade histology (HR: 1.87, 95%CI 1.04-3.38; p=.038 and HR: 2.29, 95%CI 1.07-4.01; p=.034) but not subtotal resection (HR: 1.53, 95%CI .68-3.45; p=.303 and HR: 1.75, 95%CI .52-5.96; p=.369) remained independently correlated with recurrence after an event-free PFS of at least three (n=485) and five years (n=346), respectively. Similarly, postoperative tumor volume was related with recurrence in the entire cohort (p<.001) but not beyond a follow-up of ≥ three years (p>.05). In 147 patients with a follow-up of ≥ ten years, ten recurrences occurred, and no correlation was found with any of the analyzed variables.

Conclusion

Skull base tumor location and high-grade histology but not the extent of resection should be considered when planning follow-up duration and intervals following ≥5 years after meningioma surgery. Tumor relapses following more than ten years after surgery are very rare, and corresponding predictors are lacking.
P18.02.B Influence of preoperative embolization on intraoperative parameters, hospital stay and neurocognitive outcome compared to surgery alone
Authors: Pedersen M , Eibl T , Nania A , Voit-Höhne H , Schrey M , Steiner H , Holtmannspötter M
Published: September 2022

Background

Preoperative embolization of meningiomas is used to reduce intraoperative blood loss and facilitate resection. So far, a risk-benefit stratification of this additional intervention on the neurocognitive outcome is missing. This study investigates the influence of preoperative embolization with liquid Embolisate on intraoperative parameters, length of hospital stays and functional outcome.

Material and Methods

Patients treated for intracranial meningiomas at a single center between January 2019 and June 2021 were reviewed in a retrospective matched-pair analysis. Patients were matched to group A (tumor resected) and group B (preoperatively embolized and tumor resected after 2,27 ± 3,05 days). Matching criteria were tumor diameter and location (convexity, falx cerebri or skull base, frontal, parietal, occipital, temporal). Data collection included MRI (location, tumor- and necrosis volume, edema, complications), DSA (tumor blush, arterial supply), medical history, histological, surgical, clinical course, complications, and haematological parameters, as well as neurocognitive symptoms on admission and discharge from hospital.

Results

44 patients with intracranial Meningiomas were included, divides into 2 groups, each encompassing 22 patients (mean age 62,41 years, 40,5% female). The matching criteria tumor diameter (64.21 vs. 63.55 mm, p=0.725) and tumor localisation (p=0.381) showed no significant differences. There were no significant differences in postoperative hospital stay (14.41 ± 9.5 vs. 14.25 ± 16.88 days, p=0.814) and in preoperative perifocal oedema (82% vs. 82%, p=0.397). Preoperative embolization was associated with decreased intraoperative tumor bleeding (67% vs. 14%, p=0.001, PHI= 0.534), longer duration of surgery (4:58 ± 2:44 vs. 06:07 ± 03:00 hours, p=0.037), trend for decrease in perifocal oedema (p=0.052, PHI=0,498), neurocognitive improvement on discharge from hospital (23% vs. 86%, p=0.045, PHI=0.339) and decreased of epileptic seizures (preoperative 18% vs. 18% and postoperative 23% vs. 5%). There was no increase in cumulative complication rate (p=1.0) and no long-term neurocognitive impairments associated with embolization.

Conclusion

This study suggests that preoperative embolization of intracranial meningiomas significantly decreased intraoperative tumor blood loss but is also associated to an improvement on neurocognitive abilities compared to surgery alone. Importantly, complication rate is not increased. In the future, larger studies and perhaps a randomised control trial might be of value in corroborating these findings. Furthermore, the neurocognitive symptoms should be assessed in a standardised examination form, qualitative parameters such as bleeding tendency should be supplemented by quantifiable parameters, e.g., blood loss in ml.
P18.04.A Cay10603, HDAC6 inhibitor, enhances radiosensitivity in meningioma via supressing the nuclear beta-catenin accumulation
Authors: Na J , Laney R , Hanemann C
Published: September 2022

Background

Meningioma is the most frequent primary central nervous system tumour (PCNST) which account ca 36% of all PCNST. Due to the lack of efficient chemotherapy for meningioma, radiotherapy often become a first-line treatment especially when the tumour is not operable. Radiotherapy plays a crucial role in local control but its efficacy is restricted by radioresistance and by normal tissue radiation tolerance. Therefore, developing and evaluating potential radiosensitisers to enhance therapeutic efficacy are needed.Histone deacetylase (HDACs) expression is generally increased in many cancer types and regulate the expression of numerous proteins involved in tumorigenesis. Targeting HDAC using HDAC inhibitor (HDACi) represent promising radiosensitisers that affect various biological processes, such as cell survival, apoptosis, and DNA repair.

Material and Methods

We investigated whether pre-treatment with the hydroxamate-based HDAC6 inhibitor, Cay10603, impacts radiation-induced DNA double-strand break (DSB) induction, cell survival, cell cycle arrest, and cell death using immunocytochemistry, clonogenic assay, and flow cytometry in meningioma cell lines. Low concentration (100 nM) of Cay10603 was treated 24 hr prior to high energy x-ray irradiation (2 Gy) by a medical linear accelerator (LINAC). To investigate the nuclear localisation of beta-catenin, subcellular fractionation and Western Blotting were conducted.

Results

We found that tumour cells survival was synergistically decreased after combination treatment of Cay10603 and radiation. Combination therapy induced DNA damage with activation of histone gH2AX and increased G2/M arrest compared to drug or radiation alone. Both apoptotic and necrotic cell death were increased after combination therapy. To focus on the mechanisms of action of HDAC6 inhibition followed by radiation, we further investigated nuclear localisation of beta-catenin levels. The results showed the both beta-catenin and c-myc expression in the nucleus was suppressed after combination therapy.

Conclusion

In meningioma cells, radiotherapy in combination with HDAC6 inhibitor reduces the nuclear localisation of beta-catenin and synergistically decreases cell survival. Our findings demonstrate a potential therapeutic strategy of Cay10603 to improve the radiosensitisation for meningioma cells.
P18.05.A Bevacizumab in atypical and anaplastic meningiomas: the BEMEN study
Authors: Cerretti G , Bosio A , Maccari M , Padovan M , Caccese M , Zagonel V , Lombardi G
Published: September 2022

Background

meningiomas are the most frequent primary brain tumours. The current standard treatment for atypical and anaplastic meningioma can include surgical resection and radiotherapy. Despite the high rate of relapse no systemic treatment is indicated. Few data are available regarding the effectiveness of bevacizumab (BEV) in this setting. We performed a retrospective analysis investigating the efficacy and safety of BEV in meningioma patients relapsed after receiving surgery and radiotherapy. Gene mutations were also collected

Material and Methods

we retrospectively analyzed patients treated with off-label BEV at the Veneto Institute of Oncology from July 2019 to February 2022. Major inclusion criteria were histologically-confirmed diagnosis of grade 2-3 meningioma (according to WHO 2016 classification), previous treatment with surgery and radiotherapy, no indication to further surgical reintervention or reirradiation, absence of major contraindications to the use of BEV. Data were estrapolated from local clinical records. Bevacizumab was administered at 10 or 5mg/Kg every 2 weeks (at physician’s discretion) until progressive disease/death or unacceptable toxicity. Kaplan-Meier curves were used to estimate the survival rate; CTCAE v 5.0 was used to estimate treatment-related toxicities; RANO criteria were used for radiological assessment; NGS Foundation One panel was used to examine molecular data

Results

the median follow up was 13 months (3-30 range). 26 patients were enrolled. Median age was 68 ys (29-84); male pts were 16 (61%); 61% (16 pts) with atypical meningioma, 38.5% (10 pts) with anaplastic meningioma; 27% (7 pts) had underwent 2 or more surgeries; 58% had had 2 or more RT treatments; 96.1% (25 pts) received <2 previous lines of systemic treatment. 77% (20 pts) and 23% (6) received BEV 10 and 5mg/Kg every 2 weeks, respectively. For 61% of patients (16 pts), NGS analyses were available; 62% (10 pts) harboured NF2 mutations (1 patient had a confirmed diagnosis of neurofibromatosis type 2), 23% (6 pts) CDKN2A/2B deletion, 11% (3 pts) PTEN mutation, 8% (2 pts) FGFR mutation, 8% (2 pts) JAK alteration. Overall survival (OS) rate was 82% and 62% at 6 and 12 months respectively; 6 months PFS rate was 83%. 4 patients showed PR, 11 SD, 6 PD, no patient had CR; 5 patients were not evaluable for response. Among evaluable patients the disease control rate (stability+response) was 71% and the objective response rate was 19%. Median PFS and OS were not reached19% (5 pts) experienced CTCAE grade 1 or 2 toxicity, mainly hypertension (4 pts); 1 patient experienced grade 3 hypertension.

Conclusion

BEV showed very promising activity in recurrent grade 2-3 meningioma. The treatment was well tolerated. BEV should be considered an optimal therapeutic option in this setting of meningioma patients. The NGS results might be useful in identifying targetable mutations in case of further recurrence
PHYTOCHROME-INTERACTING FACTOR 4/HEMERA-mediated thermosensory growth requires the Mediator subunit MED14
Authors: Bajracharya Abhishesh , Xi Jing , Grace Karlie F , Bayer Eden E , Grant Chloe A , Clutton Caroline H , Baerson Scott R , Agarwal Ameeta K , Qiu Yongjian
Published: September 2022

While moderately elevated ambient temperatures do not trigger stress responses in plants, they do substantially stimulate the growth of specific organs through a process known as thermomorphogenesis. The basic helix–loop–helix transcription factor PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) plays a central role in regulating thermomorphogenetic hypocotyl elongation in various plant species, including Arabidopsis (Arabidopsis thaliana). Although it is well known that PIF4 and its co-activator HEMERA (HMR) promote plant thermosensory growth by activating genes involved in the biosynthesis and signaling of the phytohormone auxin, the detailed molecular mechanism of such transcriptional activation is not clear. In this report, we investigated the role of the Mediator complex in the PIF4/HMR-mediated thermoresponsive gene expression. Through the characterization of various mutants of the Mediator complex, a tail subunit named MED14 was identified as an essential factor for thermomorphogenetic hypocotyl growth. MED14 was required for the thermal induction of PIF4 target genes but had a marginal effect on the levels of PIF4 and HMR. Further transcriptomic analyses confirmed that the expression of numerous PIF4/HMR-dependent, auxin-related genes required MED14 at warm temperatures. Moreover, PIF4 and HMR physically interacted with MED14 and both were indispensable for the association of MED14 with the promoters of these thermoresponsive genes. While PIF4 did not regulate MED14 levels, HMR was required for the transcript abundance of MED14. Taken together, these results unveil an important thermomorphogenetic mechanism, in which PIF4 and HMR recruit the Mediator complex to activate auxin-related growth-promoting genes when plants sense moderate increases in ambient temperature.
Studies on Gamma Dose Rates in Outdoor Environment and Assessment of External Exposure to Public in Stepnogorsk Area, Northern Kazakhstan
Authors: Ibrayeva Danara , Ilbekova Kuralay , Aumalikova Moldir , Kazymbet Polat , Zhumadilov Kassym , Bakhtin Meirat , Hoshi Masaharu
Published: September 2022

The present study is based on a pilot study, which showed that the Stepnogorsk area of Northern Kazakhstan represents sources of potential contamination of the living environment. The aim of the study was measurement of outdoor gamma radiation levels, activity concentration in soil samples and assessment of external exposure to the public. According to our analysis, the highest ${\boldsymbol{H}}^{\ast}$(10) values ∼2870 nGy h−1 were detected in the Aqsu school territory, which were slightly higher than the control readings for this region. The average 226Ra, 232Th and 40K activities were 617.8 ± 3.2 Bq kg−1, 188.3 ± 2.9 Bq kg−1 and 731.5 ± 6.2 Bq kg−1, respectively. The annual effective dose received by the Aqsu population ranged from 0.08 to 3.5 mSv y−1, which was found higher by an order of magnitude than the upper annual dose limit. Changes in radiation background are an unfavourable factor for the population and may possibly become potential radiation risks for long-term effects.
Exosome from BMMSC Attenuates Cardiopulmonary Bypass-Induced Acute Lung Injury Via YAP/β-Catenin Pathway: Downregulation of Pyroptosis
Authors: Zhang Taoyuan , Lu Linhe , Li Man , Zhang Ding , Yu Peng , Zhang Xinhao , Zhang Zheng , Lei Chong
Published: September 2022

Acute lung injury (ALI) accompanied with systemic inflammatory response is an important complication after cardiopulmonary bypass (CPB). Pyroptosis, which is induced by the secretion of inflammatory factors, has been implicated in ALI. However, recent studies have suggested that bone marrow mesenchymal stem cell-derived exosomes (BMMSC-Exo) can ameliorate ALI, but the mechanism is poorly understood. Therefore, we aim to examine the effects of BMMSC-Exo in CPB-induced ALI, and its underlying mechanism. CPB rat models (male Sprague-Dawley rats) were administered BMMSC-Exo intravenously before induction of ALI. Lung tissue, bronchoalveolar lavage fluid (BALF), and alveolar macrophage (AM) were collected after the treatments for further analysis, and rat AM NR8383 cells were used for in vitro study. HE staining was performed to detect macrophage infiltration. Western blot was used to detect related proteins expression. And ELISA assay was performed to investigate secretion of inflammatory factors. These results showed that BMMSC-Exo treatment ameliorated macrophage infiltration and oxidative stress, and downregulated expression of pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and GSDMD-N, in the lung tissue and AM, as well as decreased the secretion of IL-18 and IL-1β in BALF. Moreover, BMMSC-Exo activated YAP/β-catenin signaling pathway. Overall, these findings of this study indicated that BMMSC-Exo suppressed CPB-induced pyroptosis in ALI by activating YAP/β-catenin axis, which could be a novel strategy for lung protection during CPB.
First Report of Curvularia lunata (ON246070) Causing Leaf Spot Disease of Banana from Raiganj, West Bengal, India
Authors: Chowhan P. , Chakraborty A. P.
Published: September 2022

Between December 2021 and January 2022, leaf spot disease was observed on leaves of field-grown banana plants in Sarai, Raiganj, Uttar Dinajpur District, West Bengal. Symptoms first appeared as yellowish brown spots in the middle and margin of leaves. A fungus was isolated from the infected leaf onto potato dextrose agar amended with Monocef. Based on 18S rDNA partial sequencing, the fungus was identified as Curvularia lunata. Disease symptoms developed within 5 days on inoculated detached leaves, and C. lunata was reisolated from the infected spots. This is the first report of C. lunata affecting banana from Sarai.
Adalimumab versus ustekinumab as first-line biological in moderate-to-severe Crohn’s disease: real-life cohort from a tertiary referral center
Authors: Moens Annick , Alsoud Dahham , Verstockt Bram , Sabino João , Ferrante Marc , Vermeire Séverine
Published: September 2022

Background

Therapeutic options for Crohn’s disease are growing, making the choice of first-line therapy relevant. Both adalimumab and ustekinumab are effective in moderate-to-severe Crohn’s disease. The Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year trial suggested no difference in clinical or endoscopic remission at week 52 in biological-naive Crohn’s disease patients. We explored if results withstand in the real world.

Methods

We included bio-naive Crohn’s disease patients starting adalimumab or ustekinumab between 2017 and 2020. Patients had endoscopy-proven moderate-to-severe disease [Simple Endoscopic Score for Crohn’s disease (SES-CD) ≥3]. Clinical remission was defined as Harvey Bradshaw Index (HBI) <5 or physician global assessment. Endoscopic remission (SES-CD <3) and improvement (≥50% reduction in SES-CD from baseline) were assessed at W26-52. Propensity score matching was used.

Results

A total of 68 biological-naive Crohn’s disease patients were included (32 adalimumab and 32 ustekinumab) and followed for median of (IQR) 60 (33–104) weeks. Patients had significantly higher odds of achieving endoscopic remission with adalimumab than ustekinumab [adjusted odds ratio (aOR), 2.73; confidence interval (CI), 1.12–7.36; P = 0.03]. Also, more adalimumab-treated patients achieved endoscopic response, clinical remission at week 26 and 52 (aOR, 2.24; CI, 0.94–5.71; P = 0.07; aOR, 1.26; CI, 0.36–4.51; P = 0.72; aOR, 1.58; CI, 0.54–4.88; P = 0.41, respectively). Treatment persistence was not different between groups (P = 0.44). The number of adverse events was similar.

Conclusion

In a real-world cohort of biological-naive Crohn’s disease patients, adalimumab was superior to ustekinumab in achieving endoscopic remission. No differences in clinical remission at W26-52 or treatment persistence were observed. Both adalimumab and ustekinumab remain good options as first-line biologicals in moderate-to-severe Crohn’s disease.
Endoscopic submucosal dissection: a country dissemination experience and outcomes
Authors: Rodríguez-Carrasco Marta , Libânio Diogo , Pimentel-Nunes Pedro , Barreiro Pedro , Ferreira Anibal , Küttner-Magalhães Ricardo , Pinho Rolando , Boal Carvalho Pedro , Areia Miguel , Lage Jorge , Serrano Miguel , Silva João , Dias-Pereira António , Carvalho Laura , Cadime Ana Teresa , Cotter José , Carvalho João , Pedroto Isabel , Gonçalves Raquel , Chagas Cristina , Dinis-Ribeiro Mário
Published: September 2022

Objective

An increasing use of endoscopic submucosal dissection (ESD) has been reported in Western countries, although some differences in training schemes and outcomes have been described. We aimed to report the training model, implementation, and outcomes of ESD in Portugal.

Methods

All endoscopists trained at our center from our country (n = 9) were invited to a survey regarding: (a) training period; (b) ESD outcomes and (c) implementation of ESD in each respective center.

Results

All endoscopists completed the survey. Learning ESD was centered on human ESD assistance in a high-volume center during a median time of 6 months and complemented mainly by hands-on courses (89%). During the surveyed period, a total of 1229 ESD were performed, mostly in gastric locations (74%). Median complete R0 and curative resection rate were 92% (IQR, 81–96.8) and 87% (IQR, 74–93.3), respectively, and median perforation rate was 0.89% (IQR, 0.25–6.22). The main limitations encountered during the implementation of ESD were related to the lack of initial mentoring or insufficient expertise to progress to more difficult lesions.

Conclusion

Learning ESD through participation in hands-on courses and visiting high-volume centers seems to be adequate to achieve a good competence at the initial stage of ESD, which in fact is in consonance with the European Society of Gastrointestinal Endoscopy recommendations. However, mentoring is essential for technical progression, and this represents the fundamental barrier during the adoption of ESD, which may be overcome by increasing hands-on training in animal or artificial simulators, but preferably with the implementation of a structured training program.
High sustained virologic response rate after 8 weeks of direct-acting antivirals in cancer patients with chronic hepatitis C virus
Authors: Yibirin Marcel , Hosry Jeff , Yepez Guevara Eduardo , Granwehr Bruno P. , Jiang Ying , Mustafayev Khalis , Angelidakis Georgios , Torres Harrys A.
Published: September 2022

Objective

There is no prospective data on 8 weeks of direct-acting antivirals (DAA) therapy with glecaprevir/pibrentasvir (GLE/PIB) or ledipasvir/sofosbuvir (LDV/SOF) in hepatitis C virus (HCV)-infected patients with different types of malignancies. This study evaluated the efficacy and safety with 8 weeks of DAA therapy in cancer patients with chronic HCV infection.

Methods

Patients treated with DAAs at our center during 2014–2021 were included in a prospective observational study. Efficacy (sustained virologic response at 12 weeks; SVR12) and safety [adverse events and clinically significant drug-drug interactions (DDIs)] were assessed.

Results

We included 47 patients. Most were men (29; 62%), white (33; 70%), non-cirrhotic (45; 96%), and with HCV genotype 1 (38; 85%). None of the patients had HCC. The SVR12 rate was 96% (45/47; 95% CI: 86–99%) for the entire study cohort, 100% [17/17; 95% CI: 82–100%] for the patients treated with GLE/PIB and 93% [28/30; 95% CI: 79–98%] for the patients treated with LDV/SOF. Fisher’s exact test showed no significant difference in SVR12 rates between the regimens (P = 0.53). No patients had serious adverse events (grade 3–4) or treatment discontinuation. Among the 17 patients who received concomitant cancer therapy, no DDIs occurred.

Conclusion

Eight weeks of DAA therapy is highly effective and safe in HCV-infected patients with different types of malignancies and may grant access to investigational cancer therapy, broadening treatment options.
Disrupted interhemispheric functional connectivity in primary angle-closure glaucoma: a functional MRI study: voxel-mirrored homotopic connectivity in primary angle-closure glaucoma patients
Authors: Tong Yan , Zhong Yu Lin , Liu Hui , Huang Xin
Published: September 2022

The purpose of the study is to use the voxel-mirrored homotopic connectivity (VMHC) technique to explore the pattern of the interhemispheric functional connectivity in patients with primary angle-closure glaucoma (PACG). The interhemispheric functional connectivity was compared between 31 individuals with PACG and 31 healthy controls closely matched with sex, age, and educational level using the VMHC technique. Significant differences in VMHC between two groups were selected to be classification features for classifying individuals with PACG from healthy controls using the support vector machine algorithm of the machine learning. We used the permutation test analysis to assess the classification performance. In addition, the Pearson analysis was applied to explore the relationship between changed VMHC and clinical varieties in patients with PACG. Compared with healthy controls, individuals with PACG exhibited significantly lower VMHC signal values in the right calcarine, right cuneus, right superior occipital gyrus, and right postcentral gyrus [voxel level: P < 0.001, Gaussian random field correction, cluster level: P < 0.05]. Moreover, the results displayed that the total accuracy, sensitivity, and specificity of the machine learning classification were 0.758, 0.710, and 0.807, respectively (P < 0.001, nonparametric permutation test). The findings demonstrated that there is disturbed interhemispheric resting-state functional connectivity in the vision-related brain areas of individuals with PACG; and the VMHC variability can classify individuals with PACG from healthy controls with high accuracy, which provided novel evidence for understanding the neuropathological mechanism of PACG.
Jack of all trades: genome assembly of Wild Jack and comparative genomics of Artocarpus
Authors: Patil Ajinkya Bharatraj , Vajja Sai Samhitha , Raghavendra S. , Satish B.N. , Kushalappa C.G. , Vijay Nagarjun
Published: September 2022

Known as breadfruits for their diverse nutritious fruits, the Artocarpus (Moraceae) genus is prized for its high-quality timber, medicinal value, and economic importance. Breadfruits are native to Southeast Asia but have been introduced to other continents. The most commonly cultivated species areArtocarpus heterophyllus(Jackfruit) andArtocarpus altilis(Breadfruit). With numerous smaller but nutritionally comparable fruits on a large tree,Artocarpus hirsutus, also called “Wild jack” or “Ayani” is an elusive forest species endemic to Indian Western Ghats. In this study, we sequenced and assembled the whole genome ofArtocarpus hirsutussampled from sacred groves of Coorg, India. We compared our Wild jack genome with previously published Jackfruit and Breadfruit genomes to decipher demography and evolution. Demographic history reconstruction indicates a stronger effect of habitat rather than phylogeny on the population histories of these plants. Repetitive genomic regions, especially LTR Copia, strongly affected the demographic trajectory ofA. heterophyllus. Upon further investigation, we found a recent lineage-specific accumulation of LTR Copia inA. heterophyllus, which results in its larger genome size. Gene family evolution and signatures of selection identified multiple genes from starch, sucrose metabolism, plant hormone signal transduction, etc., inArtocarpusspecies. Our comparative genomic framework provides important insights by incorporating endemic species such as the Wild jack.
Predictive neural representations of naturalistic dynamic input
Authors: de Vries Ingmar E.J. , Wurm Moritz F.
Published: September 2022

Adaptive behavior such as social interaction requires our brain to predict unfolding external dynamics. While theories assume such dynamic prediction, empirical evidence is limited to static snapshots and indirect consequences of predictions. We present a dynamic extension to representational similarity analysis that uses temporally variable models to capture neural representations of unfolding events. We applied this approach to source-reconstructed magnetoencephalography (MEG) data of healthy human subjects and demonstrate both lagged and predictive neural representations of observed actions. Predictive representations exhibit a hierarchical pattern, such that high-level abstract stimulus features are predicted earlier in time, while low-level visual features are predicted closer in time to the actual sensory input. By quantifying the temporal forecast window of the brain, this approach allows investigating predictive processing of our dynamic world. It can be applied to other naturalistic stimuli (e.g., film, soundscapes, music, motor planning/execution, social interaction) and any biosignal with high temporal resolution.
The tea plant (Camellia sinensis) FLOWERING LOCUS C-like gene CsFLC1 is correlated with bud dormancy and triggers early flowering in Arabidopsis
Authors: Liu Ying , Dreni Ludovico , Zhang Haojie , Zhang Xinzhong , Li Nana , Zhang Kexin , Di Taimei , Wang Lu , Yang Yajun , Hao Xinyuan , Wang Xinchao
Published: September 2022

Flowering and bud dormancy are crucial stages in the life cycle of perennial angiosperms in temperate climates. MADS-box family genes are involved in many plant growth and development processes. Here, we identified 3 MADS-box genes in tea plant belonging to the FLOWERING LOCUS C (CsFLC) family. We monitored CsFLC1 transcription throughout the year and found that CsFLC1 was expressed at a higher level during the winter bud dormancy and flowering phases. To clarify the function of CsFLC1, we developed transgenic Arabidopsis thaliana plants heterologously expressing 35S::CsFLC1. These lines bolted and bloomed earlier than the WT (Col-0), and the seed germination rate was inversely proportional to the increased CsFLC1 expression level. RNA-seq of 35S::CsFLC1 transgenic Arabidopsis showed that many genes responding to ageing, flower development and leaf senescence were affected, and phytohormone-related pathways were especially enriched. According to the results of hormone content detection and RNA transcript level analysis, CsFLC1 controls flowering time possibly by regulating SOC1, AGL42, SEP3 and AP3 and hormone signalling, accumulation and metabolism. Our results suggest that CsFLC1 might play dual roles in flowering and winter bud dormancy and provide new insight into the molecular mechanisms of FLC in tea plants as well as other plant species.

Highlight

Three FLOWERING LOCUS C-like genes were identified in tea plants, among them CsFLC1 played dual roles in flowering and winter bud dormancy.
Ecological corridors homogenize plant root endospheric mycobiota
Authors: Hu Jie , Vandenkoornhuyse Philippe , Khalfallah Fadwa , Causse-Védrines Romain , Mony Cendrine
Published: September 2022

Ecological corridors have been shown to promote species coexistence in fragmented habitats where dispersal limits species fluxes. The corridor concept was developed and investigated mainly by focusing on macroorganisms while microorganisms, the invisible majority of biodiversity, have been disregarded.

Combining an experimental corridor-mesocosm design with high-throughput amplicon sequencing, we analyzed the effect of corridors on the dynamics of endospheric fungal assemblages associated with plant roots at metric scale over two years (i.e. at five time points).

We show that the plant symbiotic compartment was sensitive to corridor effects when the corridors were set up at a small spatial scale. The endospheric mycobiota of connected plants displayed higher species richness, lower beta-diversity, and a more deterministic assembly than the mycobiota of isolated plants. These effects became more pronounced with the development of host plants.

Biotic corridors composed of host plants may thus play a key role in the spatial dynamics of microbial community and may influence microbial diversity and related ecological functions.
Neural responses to movie naturalistic stimuli are related to listening demand in cochlear implant users
Authors: Xiu Bowen , Paul Brandon T. , Chen Joseph , Le Trung , Lin Vincent , Dimitrijevic Andrew
Published: September 2022

There is a weak relationship between clinical and self-reported speech perception outcomes in cochlear implant (CI) listeners. Such poor correspondence may be due to differences in clinical and “real-world” listening environments and stimuli. Speech sounds in the real world are often accompanied by visual cues, background environmental noise and is generally in the context of a connected conversation. The aims of this study were to determine if brain responses to naturalistic speech could index speech perception and listening demand in CI users. Accordingly, we recorded high density EEG while CI users listened/watched a naturalistic stimulus (i.e., the television show, “The Office”). We used continuous EEG to quantify “speech neural tracking” (i.e., TRFs, temporal response functions) to the television show audio track and additionally 8–12 Hz (alpha) brain rhythms commonly related to listening effort. Background noise at three different signal-to-noise ratios (SNRs), +5, +10, and +15 dB were presented to vary the difficulty of following the television show mimicking a natural noisy environment. The task included an additional condition of audio-only (no video). After each condition, participants subjectively rated listening demand and the degree of words and conversations they felt they could understand. Fifteen CI users reported progressively higher degrees of listening demand and less words and conversation with increasing background noise. Listening demand and conversation understanding in the audio-only condition was comparable to that of the highest noise condition (+5 dB). The addition of the background noise reduced the degree of speech neural tracking. Mixed effect modeling showed that listening demand and conversation understanding were correlated to cortical speech tracking such that high demand and low conversation understanding lower associated with lower amplitude TRFs. In the high noise condition, greater listening demand was negatively correlated to parietal alpha power such that higher demand was related to lower alpha power. No significant correlations were observed between TRF/alpha and clinical speech perception scores. These results are similar to previous findings showing little relationship between speech perception and quality of life in CI users. However, the physiological responses to complex natural speech may anticipate aspects of quality-of-life measures such as self-perceived listening demand.
Optimization and deoptimization of codons in SARS-CoV-2 and the implications for vaccine development
Authors: Wu Xinkai , Shan Kejia , Zan Fuwen , Tang Xiaolu , Qian Zhaohui , Lu Jian
Published: September 2022

The spread of Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 coronavirus, has progressed into a global pandemic. To date, thousands of genetic variants have been identified across SARS-CoV-2 isolates from patients. Sequence analysis reveals that the codon usage of viral sequences decreased over time but fluctuated from time to time. In this study, through evolution modeling, we found that this phenomenon might result from the virus’ preference for mutations during transmission. Using dual luciferase assays, we further discovered that the deoptimization of codons on viruses might weaken protein expression during the virus evolution, indicating that the choice of codon usage might play important role in virus fitness. Finally, given the importance of codon usage in protein expression and particularly for mRNA vaccine, we designed several omicron BA.2.12.1 and BA.4/5 spike mRNA vaccine candidates based on codon optimization, and experimentally validated their high levels of expression. Our study highlights the importance of codon usage in virus evolution and mRNA vaccine development.
Tracking canopy gap dynamics across four sites in the Brazilian Amazon
Authors: Gorgens Eric Bastos , Keller Michael , Jackson Toby D , Marra Daniel Magnabosco , Reis Cristiano Rodrigues , de Almeida Danilo Roberti Alves , Coomes David A. , Ometto Jean Pierre
Published: September 2022

Background information to give context to the study

Canopy gaps are the most evident manifestation of how disturbances disrupt forest landscapes. The size distribution and return frequency of gaps, and subsequent recovery processes, determine whether the old-growth state can be reached.

The aim or research question

We used remote sensing metrics to compare the disturbance regime of four Amazon regions based on the size distribution of gaps, their dynamics and geometric characteristics.

A brief summary of the methodology used

We assessed gap dynamics at four sites in the central, central eastern, southeastern, and northeastern regions of the Brazilian Amazon using repeated airborne laser scanning surveys. We developed a novel analysis to quantify four possible stages of gap dynamics: formation, expansion, persisting and recovering. For that, we overlapped layers of gap locations from two consecutive airborne laser scanning surveys.

Key results with some significance measures

The gap fraction in our study sites varied between 1.26% to 7.84%. All the sites have similar proportion of gaps among size classes. What notably changed between sites was not the gap size-distribution, but the relative importance of stages of gap dynamics. Growing and persisting rates were greatest in the site with the stronger seasonal variation in climate, lower annual precipitation, higher mean wind speed and higher solar radiation.

The conclusions, which address the main aims

The concept of stability reflects the tendency of a system to quickly return to a position of equilibrium when disturbed. We showed that gap dynamics varied among sites, with one example of low recovery rate contrasted to three other sites with faster recovery. Our results support that such as assessing the size distribution of gaps, investigating their return frequency and severity is crucial for understanding forest dynamics at the landscape and regional scales.