bluuebunny/crossref_metadata_2025 huggingface dataset:
P16.04.B Palliative CSF diversion in symptomatic leptomeningeal metastasis: a feasibility analysis of risks and benefits
Authors: Alhalabi O T , Unterberg A W , Younsi A
Published: September 2022

Background

Leptomeningeal metastasis (LM) represents a terminal condition in a subset of patients with primary extra-cranial malignancies. With improved survival rates under novel systemic therapies for extra-cranial primary tumors, the role of cerebrospinal fluid (CSF) diversion via ventriculo-peritoneal shunts (VP-shunt) for symptom control of hydrocephalic LM is becoming increasingly important. This study hence aimed to describe this patient cohort and weigh out benefits against adverse events of palliative VP-shunt placement.

Material and Methods

A single-center retrospective analysis of all consecutive adult patients with VP-shunt placement over a period of six years was performed and clinical data (primary disease, clinical presentation, CSF diagnostics, previous therapies) in addition to surgical data (shunt devices, surgeries, and complications) and survival data were collected. Results were compared to a ‘non-oncological’ shunt cohort and statistical analyses was performed.

Results

38 patients with a median age of 53 (18-78) years (13 males, 25 females) underwent VP-Shunt placement. The most common underlying oncological conditions were breast cancer (n=21, 55%) and non-small cell lung cancer (NSCLC, n=11, 29%). The median time between primary tumor and LM diagnosis was 23 months (0 to 180 months). 14 patients (37%) presented with end-stage disease at primary tumor diagnosis, 25 (66%) patients had cranial metastases. Most patients presented with classical symptoms of intracranial hypertension and 11 patients (38%) had already received intrathecal treatment or radiotherapy before shunting. After shunting, symptom relief was achieved in 30 patients (79%) and 24 patients (63%) were eventually discharged home after surgery. Subsequently, 63% of the shunted patients underwent systemic or radiotherapy and 55% received intrathecal therapy. Revision surgery was performed for valve malfunctions and infections (n=3, 8% for either) or distal catheter malposition (n=2, 5%) but comparison with a ‘non-oncological’ shunt cohort showed no differences in complication rates. Median survival from shunting was 2.1 months (95% CI 0.5 to 3 months).

Conclusion

VP-shunt placement could relieve symptoms of intracranial hypertension secondary to LM of primary solid tumors without a higher risk of shunt complications compared to non-oncological patients, with many LM patients persuing further oncologic therapy. However, decision-making regarding VP-shunt placement in LM patients still retains a palliative nature.
P17.02.A IPAX-1: phase 1/2 study of131I-iodo-phenylalanine (131IIPA) combined with external radiation therapy as treatment for patients with relapsed glioblastoma
Authors: Pichler J , Leibetseder A , Höllmüller I , Traub-Weidinger T , Fitz F , Geinitz H , Feichtinger J , Brown T , Hayward C
Published: September 2022

Background

A novel therapeutic approach using molecularly targeted radiation is currently in development for patients with recurrent GBM. Many tumor types, including GBM, overexpress the L-type amino transporter 1 (LAT-1)4, which is able to internalize the small-molecule amino acid derivative, 4-L-[131I] iodo-phenylalanine (131I-IPA). In preclinical research, combining 131I-IPA with external radiation therapy (XRT) yielded additive cytotoxic effects. Tumoral accumulation of 131I-IPA was confirmed in a proof-of-principle study using single doses of 2-7 GBq 131I-IPA as a monotherapy or in combination with XRT in patients with recurrent GBM. The objective of the IPAX-1 study was to evaluate the safety, tolerability, dosing schedule, and preliminary efficacy of 131I-IPA in combination with second-line radiotherapy in patients with recurrent GBM.

Methods

IPAX-1 is a multi-center, open-label, single-arm, dose-finding phase 1/2 study. Key inclusion criteria: 1. Confirmed histological diagnosis of GBM with evidence of first recurrence 2. History of GBM standard therapy 3. ≥ 6 months since end of first-line XRT 4. Pathologically increased amino acid tumor uptake shown by molecular imaging 5. Current indication for repeat radiation 6. Gross tumour volume of up to 4.8 cm diameter. Treatment: In phase 1 of the study patients received intravenous 131I-IPA at a dose level of 2 GBq administered in one of three different dosing regimens: single dose group with 2 GBq before radiation, 3 (f)-fractionated-parallel group: 3 x 0.67 GBq during XRT and 3 (f)-fractionated-sequential group: 0.67 GBq x 1 → XRT → 0.67 GBq x 2. XRT is delivered in 18 fractions of 2 Gy each.

Results

10 patients were randomized; one patient with Covid related death was withdrawn from analysis. Survival from start of TLX101 therapy showed mPFS2 of 4.33 M (95% -CI 4.18 - 4.48), PFS-6: 18 % and mOS2 of 15.97 M (95% -CI 2.9 - 29.1) at data lock 09/2021. Updated results will be presented at the meeting.

Conclusion

There were no clinically relevant laboratory changes over time. Urinalysis, vital signs, and ECG did not show any clinically relevant changes from baseline. There were no notable differences in safety and tolerability between groups. Injections of single or fractionated doses of 131I-IPA containing a total activity of 2 GBq in combination with XRT in patients with recurrent GBM were safe and well tolerated. Survival data look promising; extension cohort will be treated in a phase II study in Linz; phase 1/2 study in first line setting is planned.
P17.04.B Combination of Trofosfamide and Etoposide in Recurrent Glioma
Authors: Schmidt T , Agkatsev S , Feldheim J , Oster C , Blau T , Sure U , Keyvani K , Kleinschnitz C , Stuschke M , Hermann K , Deuschl C , Scheffler B , Kebir S , Glas M , Lazaridis L
Published: September 2022

Background

Disease relapse almost inevitably occurs in patients with adult-type diffuse glioma. Standard of care treatment options at tumor relapse are still not well defined. Frequently used drugs for adult-type diffuse glioma recurrence include lomustine (CCNU) and bevacizumab. Few studies indicate that the combination of trofosfamide/etoposide, given their high lipid solubility with good blood-brain barrier penetrance, may be feasible in pediatric glioblastoma patients. In this retrospective analysis, we determined tolerability and feasibility of combined trofosfamide/etoposide treatment at disease recurrence of patients with adult-type diffuse glioma.

Material and Methods

We collected clinicopathological data from adult patients with adult-type diffuse glioma treated with the combination of trofosfamide/etoposide at the Division of Clinical Neurooncology at the University Hospital Essen. Only those patients were considered eligible who received trofosfamide/etoposide treatment for more than four weeks (one course). Trofosfamide (100mg/m2/day) and Etoposide (25mg/m2/day) was administered orally in a “one week on, one week off” scheme. A cohort of patients receiving empiric treatment at the investigators’ discretion balanced for tumor entity and canonical prognostic factors (number of previous treatments, MGMT promoter methylation, IDH mutation status, KPS, age, extent of resection) served as control. We collected toxicity data as it pertained to CTCAE (Common Terminology Criteria for Adverse Events, version 5.0) and survival data to explore putative efficacy.

Results

A total of 33 patients were eligible for this analysis. In the IDH wild-type glioblastoma (n=18) subgroup, median progression-free survival (3.8 months versus 2.9 months, HR: 2.09, 95% CI: 1.010-4.312, p=0.0227; PFS-6: 39% versus 6%) and median overall survival (10.4 months versus 5.7 months, HR: 3.05, 95% CI: 1.393-6.655, p=0.0008) were significantly prolonged as compared to the control cohort. In a multivariable Cox regression analysis, treatment with trofosfamide/etoposide emerged as statistically significant prognostic marker regarding progression-free survival and overall survival. We observed high-grade adverse events (CTCAE grade≥III ) in 21 (64%) of all recurrent glioma patients with hematotoxicity comprising most adverse events (n=18, 86%). Lymphopenia was by far the most observed hematotoxic adverse event (n=13, 62%). Among non-hematologic high-grade adverse events was transaminase elevation (n=3, 14%).

Conclusion

This study provides first indication that the combination of trofosfamide/etoposide is safe in patients with adult-type diffuse gliomas and may be associated with prolonged survival in adult patients with recurrent IDH wildtype glioblastoma. Our data provide a reasonable rationale for follow-up of a larger cohort in a prospective controlled trial.
P17.12.B HOXD13 gene plays a role as a putative master epigenetic regulator in glioma recurrence and progression
Authors: Morosini N S , Sabedot T S , Cazacu S L , deCarvalho A , Noushmehr H
Published: September 2022

Background

Adult diffuse glioma is a heterogenous brain tumor group that has malignant potential and recurring properties. Glioma CpG island methylator phenotype (G-CIMP) associated with chromatin remodeling encompasses two different methylation degrees: G-CIMP-high and G-CIMP-low that have high levels of DNA methylation and loss of DNA methylation, respectively. G-CIMP-high confers a more favorable prognosis and better predictive values by altering transcriptional dynamics and inhibiting the gene expression. However, some IDH-mutant G-CIMP-high undergo a demethylation process progressing to G-CIMP-low leading to tumor recurrence and aggressiveness.

Material and Methods

We have performed Chromatin Immunoprecipitation Sequencing (ChIP-Seq) on DNA extracted from nine (9) fresh frozen primary tumor tissues belonging to G-CIMP-high group and four (4) belonging to G-CIMP-low group. We have processed the sequencing data by using FastQC (v.:0.11.5), bwa-mem (v.:0.7.15) and picard tool (v.:2.7.1). The ChIP-seq peaks and the differentially bound peaks were obtained using MACS2 (v.:2.1.1) and DiffBind (v.:3.4.11), respectively. We have integrated transcriptomic, epigenomic and genomic data to investigate the impact of H3K4me3 and H3K27ac in the epigenome of G-CIMP-low and high tumors.

Results

Initial results showed that the differentially bound H3K27ac and H3K4me3 peak gains and losses are located mainly in intronic and intergenic regions. The integration between epigenetic and transcriptomic data revealed that the promoter of the HOXD13 gene upregulated in GCIMP-low presents an active regulatory region and is enriched by H3K27ac and H3K4me3 sites. We were able to identify that GCIMP-low, in addition to presenting more downregulated genes than GCIMP-high, also has greater affinity to the H3K27ac peaks. In GCIMP-low, we identified 312 promoter regions significantly enriched by the epigenetic biomarker H3K27ac and 67 promoters with loss of affinity for H3K27ac, with the regions enriched by H3K27ac highly associated with the presence H3K4me3 marks. Functional genomic analysis targeting HOXD13 by using CRISPR in a representative glioma cell line shows that HOXD13 is critical for impairing the proliferative state that drives glioma progression.Conclusion: We mapped the enrichment of histone modifications in the TSS of differentially expressed genes in G-CIMP-high and G-CIMP-low identifying both the susceptibility of GIMP-low to interact with H3K27ac and the fact that the progression of GCIMP-high to G-CIMP-low can be explained by the association between H3K27ac gain and the inhibition of gene expression. Also, we predicted the HOXD13 gene as a putative master epigenetic regulator of the G-CIMP demethylation process and, consequently, of tumor recurrence and progression, over time.
P17.14.B Strategy of the recurrent Glioblastoma treatment. Three neuro-oncology centers study
Authors: Kalita O , Kazda T , Reguli S , Jancalek R , Fadrus P , Krska L , Slachta M , Valosek J , Vrbkova J , Hrabalek L , Smrcka M , Lipina R
Published: September 2022

Background

The prognosis for patients with Glioblastoma (GBM) remains dismal. The most aggressive multimodal therapy (maximally radical and safe tumor resection, followed by the Stupp protocol oncotherapy) has yielded the best treatment outcomes. Notwithstanding the slowly prolonged patient′s overall survival, this tumor inevitable recurs. An optimal therapy of the recurrent GBM is still a controversial theme.The aim of our study is to evaluate our treatment strategy of recurrent GBM.

Material and Methods

For this study, we retrospectively selected a group of resected recurrent GBM patients in a period from June 1, 2009 to December 31, 2019, which were treated in tree Czech neuro-oncologic centers. All patients underwent early post-surgical MRI (within 72 h) to determine resection radicality. Following resection, patients received periodic checkups with MRI every 3 months until death. Patients with psedoprogession were excluded. Information about all surgeries, oncotherapies, patient clinical condition, MRI, PET/CT, and results of histological, immunohistochemical, molecular genetic, and cytogenetic investigations was gathered.We consider surgery for recurrent GBM in case, if:

1.The tumor volume increasing > 20-30% or tumor rediscovery after radiologic disappearing.

2.Clinic condition - Karnofsky score (KS) ≥ 70% and Performance status (PS) WHO ≤ gr. 2.

3.Localized tumor, without multilfocality.

4.Assumed the least tumor volume reduction > 80%.

Results

We gathered 122 patients with recurrent GBM, 98,9% of tumors was determined as wild-type, age median was 53,36 years. All patients underwent Stupp protocol oncotherapy after prime surgery. Median of OS from prime surgery was 21 months (15.8, 29.6). The best results proved a surgery of GBM recurrency proceeding more than 6 months after diagnosis. OS2 (from redo up to the death) was 7.4 months (6.41, 11.3). 43.3% of patients recalled temozolomide chemotherapy. We confirmed positive link between OS and resection radicality, negative relations between OS and a postoperative neurologic deficits. Only limited relation was presented between OS and repeated oncotherapy. Relation to the further histologic, imunohistochemic, cytogenetic and molecular markers will be discussed.

Conclusion

Due to the common unfavorable outcomes of GBM therapy, out of despair, we often decided for repeated surgery. The aim of our study was avoid ineffective surgical overtreatment. The best results of surgery yield right selected recurrent GBMs. Surgery of GBM regrown during initial oncotherapy (6 months after prime surgery) presented unsatisfactory effects. Positive effect of the surgical radicality and clinic status were confirmed. Again, necessity of second-line oncotherapy has been emerged. Supported by Ministry of Health of the Czech Republic, grant nr. NV19- 04-00281 and grant nr. NU21-03-00195
P17.16.B Additional antitumoral activity of TTFields stimulation and Chloride Intracellular Channel 1 inhibition in human glioblastoma primary culture
Authors: Mazzanti M , Castiglione S , Mercurio C A , Cannavale G , Verduci I , Cianci F
Published: September 2022

Background

Glioblastoma relapse inevitably occurs in the majority of patients after surgery. Chemo- and radiotherapy are in most cases ineffective, while Tumor Treating Fields (TTFields) therapy delays average tumor recurrence by a few months. It is widely accepted that tumor reappearance is a result of the proliferation of residual glioblastoma stem cell (GSC) subpopulation, which escaped surgery. Previous experiments demonstrated that inhibition of the membrane form of Chloride Intracellular Channel 1 (tmCLIC1) is particularly efficient to hit GSCs in glioblastoma human primary cultures. tmCLIC1 is an ideal target as it is express only in the tumor cell membranes. tmCLIC1 blockage slowdown GSC cell cycle at G1/S transition. On the contrary, TTFields act mainly during G2/M progression. The objective of our study is to test the therapeutic potential of combining TTFields exposure with the inhibition of the protein transmembrane Chloride Intracellular Channel 1 (tmCLIC1), which is crucial for GSCs proliferation.

Material and Methods

Cell preparation: human primary culture from patients’ biopsies. Stimulation device: NOVOCURE Inovitro system®. Stimulation procedure: long-term TTFields stimulation in in-vitro experiments mimics glioblastoma cells’ recrudescence. Analysis: cytofluorimetry for stem cell recognition, cell-cycle progression, and cell count.

Results

Cell growth is inhibited after the first three days of TTFields exposure. However, despite the chronic presence of TTFields stimulation in prolonged experiments, glioblastoma cells reestablish the ability to proliferate. At the end of twelve days, exponentially growing cells show an increase in stemness markers, a drop in the membrane resistance with a related increase of membrane current, and an average depolarized membrane potential. Twelve days of TTFields treatment resulted in a progressive increase in GSCs in the tumor cell population from 10% to more than 30%. Thus, experiments have been designed to combine TTFields stimulation with tmCLIC1 inhibition. This would include in the treatment of the vast majority of the glioblastoma cell population. After twelve days, the parallel antiproliferative activities show a complete impairment in cell proliferation.

Conclusion

The additive effect of TTFields stimulation and tmCLIC1 ion channel inhibition could represent an efficacious step forward to optimize an antitumoral therapy against glioblastoma expansion.
P17.19.B Incidence of treatment-associated imaging changes in newly diagnosed MGMT promoter-methylated glioblastoma treated with cilengitide (EORTC 26071 - CENTRIC study): interim analysis
Authors: Flies C M , Friedrich M , Lohmann P , van Garderen K , Smits M , Tonn J C , Weller M , Galldiks N , Snijders T J
Published: September 2022

Background

In patients with glioblastoma, radiological recurrence of enhancing tissue after chemoradiotherapy can originate from progressive disease (PD) or from pseudoprogression/treatment-associated changes. There are no widely approved consensus criteria for treatment-associated changes. In the randomised EORTC-CENTRIC study (NCT00689221), patients with MGMT promoter-methylated glioblastoma were treated with chemoradiotherapy or chemoradiotherapy with cilengitide, an integrin inhibitor. We assessed the rate of treatment-associated changes in these groups according to the modified response assessment in neuro-oncology (RANO) criteria of 2017.

Methods

CENTRIC patients from both study arms with ≥3 follow-up MRIs were included. Preliminary PD (PPD) was defined as a ≥25% increase of the sum of perpendicular diameter (SPD) of a new or increasing lesion compared to baseline or nadir on the T1-MRI with gadolinium. Subsequent PD was defined as a second ≥25% increase of the SPD, at least 4 weeks later, or as a new lesion outside the radiation field. Treatment-associated changes were defined as stabilisation on ≥2 follow-up MRIs after PPD, each one 4 weeks later, or partial/complete regression on ≥1 follow-up MRI 4 weeks later.

Results

In total, 4,051 MRIs from 584 patients were available. This interim analysis included data on 462 patients with similar proportions in the cilengitide and control arm (50.9% and 49.1%). Due to missing MRIs or values, 128 were excluded. Of the remaining 334 patients, 157 (47%) patients showed RANO measurable disease at baseline or nadir (median SPD, 0mm2; interquartile range (IQR) 552.1 (0-552.1). After chemoradiotherapy with or without cilengitide, PPD occurred in 214 patients (64.1%) after a median time of 6.08 months after finishing radiation (IQR 11.4 (2.4-13.8), and 3.65 months after baseline or nadir (IQR 6.4 (2.1-8.5). After follow-up of these 214 patients, treatment-associated changes were diagnosed in 62 (18.6%) and PD was diagnosed in 48 (14.4%). The remaining 104 (31.1%) patients had no further follow-up MRI after PPD, mostly because a clinical decision to call PD was made. In the cilengitide group of 178 patients, 37 (20.8%) patients developed treatment-associated changes, and 23 (12.9%) patients developed PD, whereas in the control group of 156 patients, 25 (16%) patients developed treatment-associated changes, and 25 (16%) patients PD.

Conclusion

With the modified RANO criteria, the rate of treatment-associated changes was low compared to previous studies in newly diagnosed MGMT promoter-methylated glioblastoma. This rate did not change with addition of cilengitide. RANO-recommended radiological follow-up was not always awaited, which reflects clinical practice. Full data will be presented.
P18.09.A Single-session stereotactic radiosurgery for large parasellar meningiomas
Authors: Emad Eldin R M , Abdel Karim K M , Reda W A , Tawadros S R , Nabil A M , El Shehaby A M N
Published: September 2022

Background

The purpose of this study is to assess the long-term efficacy and safety of single-session stereotactic radiosurgery for large (10 cc or more) perioptic intracranial benign meningiomas.

Material and Methods

In this retrospective study we included 175 patients with large perioptic benign meningiomas (≥ 10 cc) who were treated by single-session SRS. Perioptic meningiomas were defined as meningiomas touching, compressing or within 3 mm of the optic pathway. The median tumor volume was 15 (10-57.3 cc (IQR 8.4 cc)). The median prescription dose was 12 Gy (9-14 Gy (IQR 1 Gy)).

Results

The median follow up period was 72 months (13-217 months (IQR 65 months)). The tumor control rate was 92%. The PFS at 5- and 10- years was 97% and 80%. Favorable (better/stable) visual outcome was reported in 169 patients (97%) and unfavorable (worse) outcome in 6 patients (3%). Temporary adverse radiation effects were observed in 21 patients (12%) but only 7 (4%) were symptomatic. Sixty-three patients had a blind/non-useful eye according the pre-treatment visual field examination. Visual improvement was observed in blind/non-useful eye in 17 patients (27%) while vision remained unchanged in 46 patients (73%). Ocular nerve palsy improved in 36 patients (61%). Tumor shrinkage was not a prerequisite for cranial nerve improvement.

Conclusion

Stereotactic radiosurgery provides an effective and safe treatment option for large perioptic meningiomas.
Wildsoydb DataHub: a platform for accessing soybean multiomic datasets across multiple reference genomes
Authors: Xiao Zhixia , Wang Qianwen , Li Man-Wah , Huang Mingkun , Wang Zhili , Xie Min , Varshney Rajeev K , Nguyen Henry T , Chan Ting-Fung , Lam Hon-Ming
Published: September 2022

The Wildsoydb DataHub is an integrated interface for biologists and breeders to access soybean genomic resources easily, allowing them to fully utilize the results of genomic research.
Fluxapyroxad Resistance Mechanisms in Sclerotinia sclerotiorum
Authors: Wang Yanfen , Lu Ninghai , Wang Kuaikuai , Li Yinna , Zhang Mengli , Liu Shuang , Li Yanling , Zhou Feng
Published: September 2022

The necrotrophic pathogen Sclerotinia sclerotiorum has a global distribution and a wide host range, making it one of the most damaging and economically important of all plant pathogens. The current study found that fluxapyroxad, a typical succinate dehydrogenase inhibitor fungicide, had a strong inhibitory effect against S. sclerotiorum, with mean effective concentration for 50% inhibition (EC50) values ranging from 0.021 to 0.095 µg/ml. Further investigation of five highly resistant S. sclerotiorum mutants, with EC50 values of 12.37 to 31.36 µg/ml, found that fluxapyroxad resistance was accompanied by a certain cost to fitness. All of the mutants were found to have significantly (P < 0.05) reduced mycelial growth and altered sclerotia production in artificial culture, as well as reduced pathogenicity, compared with wild-type isolates, with one mutant completely losing the capacity to infect detached soybean leaves. Sequence analysis demonstrated that four of the mutants had point mutations leading to amino acid changes in the SsSdhB subunit of the fungicide target protein succinate dehydrogenase. In addition, two of the mutants were also found to have amino acid changes in the predicted sequence of their SsSdhD subunit, while the fifth mutant had no changes in any of its SsSdh sequences, indicating that an alternative mechanism might be responsible for the observed resistance in this mutant. No cross-resistance was found between fluxapyroxad and any of the other fungicides tested, including tebuconazole, prochloraz, dimethachlone, carbendazim, procymidone, pyraclostrobin, boscalid, fluazinam, fludioxonil, and cyprodinil, which indicates that fluxapyroxad has great potential as an alternative method of control for the Sclerotinia stem rot caused by S. sclerotiorum, and which could provide ongoing protection to the soybean fields of China.
Risk factors for decompensation and death following umbilical hernia repair in patients with end-stage liver disease
Authors: Malik Abdullah K. , Varghese Chris , Pandanaboyana Sanjay , Sen Gourab , Robinson Stuart , McPherson Stuart , Dyson Jessica , Manas Derek M. , Masson Steven , Hammond John S. ,   on behalf of the Newcastle Liver Unit
Published: September 2022

Introduction

Symptomatic umbilical hernias are a common cause of morbidity and mortality in patients with cirrhosis and end-stage liver disease (ESLD). This study set out to characterise the factors predicting outcome following repair of symptomatic umbilical hernias in ESLD at a single institution.

Methods

A retrospective review was performed of all patients with ESLD who underwent repair of a symptomatic umbilical hernia between 1998 and 2020. Overall survival was predicted using the Kaplan–Meier method. Logistic regression was used to determine predictors of decompensation and 30-day, 90-day and 1-year mortality.

Results

One-hundred-and-eight patients with ESLD underwent umbilical hernia repair (emergency n = 78, 72.2%). Transjugular shunting was performed in 29 patients (26.9%). Decompensation occurred in 44 patients (40.7%) and was predicted by emergency surgery (OR, 13.29; P = 0.001). Length of stay was shorter in elective patients compared to emergency patients (3-days vs. 7-days; P = 0.003). Thirty-day, 90-day and 1-year survival was 95.2, 93.2 and 85.4%, respectively. Model for ESLD score >15 predicted 90-day mortality (OR, 18.48; P = 0.030) and hyponatraemia predicted 1-year mortality (OR, 5.31; P = 0.047). Transjugular shunting predicted survival at 1 year (OR, 0.15; P = 0.038).

Conclusions

Repair of symptomatic umbilical hernias in patients with ESLD can be undertaken with acceptable outcomes in a specialist centre, however, this remains a high-risk intervention. Patients undergoing emergency repair are more likely to decompensate postoperatively, develop wound-related problems and have a longer length of stay. Transjugular shunting may confer a benefit to survival, but further prospective trials are warranted.
The association between temperature, heart rate, and respiratory rate in children aged under 16 years attending urgent and emergency care settings
Authors: Heal Calvin , Harvey Anna , Brown Stephen , Rowland Andrew Graeme , Roland Damian
Published: September 2022

Background and importance

Body temperature is considered an independent determinant of respiratory rate and heart rate; however, there is limited scientific evidence regarding the association. This study aimed to assess the association between temperature, and heart rate and respiratory rate in children.

Objective

The objective of this study was to validate earlier findings that body temperature causes an increase of approximately 10 bpm rise in heart rate per 1 °C rise in temperature, in children aged under 16 years old.

Design

A prospective study using anonymised prospectively collected patient data of 188 635 attendances, retrospectively extracted from electronic patient records.

Settings and participants

Four Emergency or Urgent Care Departments in the North West of England. Participants were children and young people aged 0–16 years old who attended one of the four sites over a period of 3 years.

Outcome measures and analysis

Multiple linear regression models, adjusted for prespecified confounders (including oxygen saturation, heart rate, respiratory rate, site of attendance, age), were used to examine the influence of various variables on heart rate and respiratory rate.

Main results

Among the 235 909 patient visits (median age 5) included, the mean temperature was 37.0 (SD, 0.8). Mean heart rate and respiratory rate were 115.6 (SD, 29.0) and 26.9 (SD, 8.3), respectively. For every 1 °C increase in temperature, heart rate will on average be 12.3 bpm higher (95% CI, 12.2–12.4), after accounting for oxygen saturation, location of attendance, and age. For every 1 °C increase in temperature, there is on average a 0.3% decrease (95% CI, 0.2–0.4%) in respiratory rate.

Conclusion

In this study on children attending urgent and emergency care settings, there was an independent association between temperature and heart rate but not between temperature and respiratory rate.
Dl-3-n-butylphthalide prevents chronic restraint stress-induced depression-like behaviors and cognitive impairment via regulating CaMKII/CREB/BDNF signaling pathway in hippocampus
Authors: Shen Jun , Yang Lu , Wei Wenshi
Published: September 2022

Background

Stress is not scarce in peoples’ daily life that may result in mental diseases and cognitive impairments. Chronic restraint stress (CRS) is a well-validated animal model used to investigate the mechanism of stress-associated depression and cognitive impairments. Dl-3-n-butylphthalide (NBP) possesses anti-oxidant, anti-inflammatory and anti-apoptotic, promoting neurogenesis and neuroplasticity that exerts neuroprotective effects. However, the effects of NBP on CRS-induced depression and cognitive impairments remain unclear.

Methods

C57BL/6 male mice were randomly divided into the control group, stress group and stress+NBP group. Mice were exposed to CRS for three consecutive weeks and mice in the NBP treatment group were administered with NBP before the CRS procedure. After that, depression and cognition behaviors were evaluated followed by phosphorylation of Ca2+/calmodulin-dependent protein kinase II (p-CaMKII), phosphorylation of cAMP-response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) proteins expression, immunohistochemistry of hippocampal postsynaptic density 95 (PSD95) and synaptophysin, and hippocampal morphology.

Results

Our results showed that mice exhibited depression-like behaviors and cognitive deficits after 3 weeks exposure to CRS. Additionally, CRS downregulated CaMKII/CREB/BDNF signaling pathway, reduced PSD95 and synaptophysin expression and induced hippocampal CA1 and dentate gyrus ment significantly reversed the hippocampal pathological and molecular changes induced by CRS.

Conclusion

In conclusion, these results reveal that NBP exerts a neuroprotective effect on depression and cognitive deficit through activating CaMKII/CREB/BDNF pathway, enhancing PSD95 and synaptophysin expression and protecting hippocampal morphology.
A matter of availability: Neural representations of task-relevant stimulus features are sharper when stimuli are memorized rather than perceived
Authors: Chota Samson , Gayet Surya , Kenemans J. Leon , Olivers Chris N.L. , Van der Stigchel Stefan
Published: September 2022

Our visual environment is relatively stable over time and an optimized visual system ought to capitalize on this by not devoting any representational resources to objects that are still present. Subjective experience, however, suggests that externally available (i.e., perceived) information is more strongly represented in neural signals than memorized information. To distinguish between these possibilities, we use EEG multivariate pattern analysis to quantify the strength of representation of task-relevant features (color or spatial frequency) in anticipation of a change-detection task. Perceptual availability was manipulated between experimental blocks by either keeping the stimulus on the screen during a two second delay period (perception) or removing it shortly after its initial presentation for the same time period (memory). We find that task-relevant (i.e., attended) memorized features are more strongly represented than irrelevant features. More importantly, we find significantly weaker representations for available (perceived and attended) features than for unavailable (memorized and attended) features. Contrary to what subjective experience suggests, our findings demonstrate that vividly perceived and attended stimuli elicit weaker neural representations (in terms of detectable multivariate information) than stimuli maintained in visual working memory. We hypothesize that an efficient visual system spends little of its limited resources on the internal representation of information that is externally available anyway.
Compartmentation of Putrescine Synthesis in Plants
Authors: Joshi Kumud , Ahmed Sheaza , Ge Lingxiao , Phuntumart Vipaporn , Kalinoski Andrea , Morris Paul F.
Published: September 2022

Three plant pathways for the synthesis of putrescine have been described to date. These are the synthesis of putrescine from ornithine, by ornithine decarboxylase (ODC); and the synthesis of putrescine from arginine by arginine decarboxylase, agmatine iminohydrolase (AIH) and N-carbamoylputrescine amidohydrolase (NLP1); or arginine decarboxylase and agmatinase. Several enzymes associated with putrescine synthesis have yet to be localized. Here we showed that ODC in soybeans and rice was localized to the ER. In rice, agmatinase is localized to the mitochondria. In A. thaliana there are five isoforms of AIH and three isoforms of NLP1. Stable GFP-tagged transformants of the longest isoforms of AIH and NLP1 showed that both proteins were localized to the ER in leaves and roots of A. thaliana. Four of the isoforms of AIH and all of the isoforms of NLP1 were localized to the ER. However, AIH1.4 was localized to both the ER and the chloroplast. Combining these results with other published data, reveal that putrescine synthesis is excluded from the cytoplasm and is spatially localized to the chloroplast, ER and likely the mitochondria. Synthesis of putrescine in the ER may facilitate cell to cell transport via plasmodesmata, or secretion via vesicles. Differential expression of these pathways may enable putrescine-mediated activation of hormone-responsive genes.
Sustainability practices in manufacturing companies: analysis of an emerging economy
Authors: Rampasso Izabela Simon , Quelhas Osvaldo Luiz Gonçalves , Ganga Gilberto Miller Devós , Pavan Serafim Milena , Simão Victor Gomes , Costa Luiz Felipe M. , Anholon Rosley
Published: September 2022

Purpose

Considering the high impacts caused by manufacturers on sustainability, this research aims to analyse how Brazilian manufacturing companies deal with sustainability issues. To do this, sustainability parameters are analysed to verify possible improvement opportunities.

Design/methodology/approach

This research uses Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) and grey relational analysis (GRA) to analyse data from a survey with Brazilian professionals regarding aspects of sustainability in Brazilian manufacturers. The average score levels and the ranking of these aspects are evaluated.

Findings

Through the analysis performed, it was possible to verify that manufacturers in Brazil still have a long path to travel in the search for sustainability. Comparatively, it was observed that practices related to local communities received the lowest scores, on average. In contrast, on average, practices related to productivity and efficiency, occupational accidents and diseases, and compliance with environmental legislation received the highest scores.

Practical implications

The results presented in this paper show that there are several improvement opportunities to be sought by Brazilian manufacturing companies regarding sustainability aspects. Particular attention should be given to local community practices. Besides companies, policymakers can also use this analysis to guide their future actions, encouraging manufacturing companies to better support the local community. Researchers can use the instrument of analysis (TOPSIS and GRA) to analyse other realities and compare them with the findings presented.

Originality/value

The analysis of Brazilian manufacturing companies’ reality regarding sustainability practices and considering a model based on Global Reporting Initiative (GRI) and Brazilian Institute of Corporate Governance (IBGC) is novel in the literature. The use of TOPSIS and GRA, as well as comparing their findings, generated interesting insights for companies, policymakers and researchers. The analysis presented shows the need for more significant concern for local communities and can be used to support further debates and action plans to minimise this gap.
Leader secure-base support and organizational learning culture: synergetic effects on employee state promotion focus and approach job crafting
Authors: Tu Yan , Jiang Lixin , Long Lirong , Wang Linlin
Published: September 2022

Purpose

Leader secure-base support, consisting of leader availability, noninterference and encouragement of growth, has important implications for stimulating employee proactivity. This study is aimed at examining whether, why and when leader secure-base support may motivate employees to engage in approach job crafting behavior. Drawing upon regulatory focus theory, we propose leader secure-base support is positively associated with employee approach job crafting via employee state promotion focus. Based on cue consistency theory, we further examine the moderating role of organizational learning culture in the associations of leader secure-base support with employee state promotion focus and subsequent approach job crafting.

Design/methodology/approach

Two-wave data were collected from 281 Chinese workers. Path analyses with Mplus 7 were conducted to test the hypotheses.

Findings

As predicted, we found that leader secure-base support was positively related to employee state promotion focus and, in turn, facilitated employee approach job crafting. Moreover, organizational learning culture accentuated the impact of leader secure-base support on employee job crafting process.

Originality/value

This study is the first to examine the influence of leader secure-base support on employee job crafting. It also identifies a boundary condition for such an influence.
Differences in the organizational-commitment–rewards relationship between Chinese managers and Japanese expatriates in manufacturing companies in China
Authors: Kokubun Keisuke , Yasui Misako
Published: September 2022

Purpose

As China attracts more and more foreign enterprises today, it is getting more important to consider how to enhance the organizational commitment (OC) of host country employees. This paper aims to examine the differences in the relationship between OC and rewards among Chinese managers and Japanese expatriates who work for Japanese manufacturing companies in China.

Design/methodology/approach

Hierarchical regression analysis was used to analyze survey data gathered from 539 Chinese managers and 354 Japanese expatriates working for a total of 19 Japanese manufacturing companies in China.

Findings

The findings reveal that, for Chinese managers, role clarity had a stronger influence and autonomy had a weaker influence on OC than for Japanese expatriates. A possible reason is the ethnocentric culture of Japanese companies that leads to Japanese expatriates not sufficiently empowering local human resources. Moreover, there was no difference between senior- and junior-level Chinese managers in the association of any kind of reward with OC.

Research limitations/implications

The most significant limitation concerns its generalizability. The authors recommend that future research use other nations' expatriates as reference groups to objectively clarify the characteristics of Chinese workers, thus testing the validity of this research.

Practical implications

The results of this research may be used to reshape future human-resource-management practices in several types of the company located in China to facilitate attracting and employing the employees most able to make long-term contributions to the company.

Originality/value

Although previous research has elucidated OC–rewards relation in particular countries, it has not met the potential requirements of the expatriates who face the difference in OC–rewards relation with host country national managers. In this sense, to the best of the authors’ knowledge, this research was the first attempt to tackle this theme by contributing to the literature.
The association of physical development density, prevalence and types of microbes in colonized façade finishes in Enugu metropolis, Nigeria
Authors: Isiofia Lawrence A. , Nna Emmanuel , Uzuegbunam Francis O. , Ibem Eziyi O.
Published: September 2022

Purpose

This research examines the association of physical development density, prevalence and types of microbes in colonized façade finishes of buildings in Enugu metropolis, Nigeria.

Design/methodology/approach

Survey and experimental research designs were adopted. A total of 383 buildings were investigated with samples collected from those with colonized façade finishes. The microbes were identified using the standard procedure for genomic sequencing with descriptive statistics, and the chi-square test used to analyse the data.

Findings

The results revealed a 64% prevalence of microbial colonization and a significant association between this and physical development density with 71.0% of the colonized buildings located in high-density neighbourhoods of the metropolis. The sequencing also showed 24 different microbes with Trichophyton tonsurans, Trichophyton mentagrophytes and Trichoderma harzianum species being the most common in the colonized façade finishes.

Practical implications

The research informs building professionals and owners of the specific microbes involved in the colonization of façade finishes of buildings in high-density urban areas. It also provides a clue about the nature of damages and defects associated with microbial colonization of building façades and the type of biocide additives required for the production of microbial-resistant façade finishes in the hot-humid tropical environment of Nigeria and beyond.

Originality/value

The study has shown that there is a significant relationship between the intensity of urban land use and microbial colonization of façade finishes of buildings. It also identified some new or less known microbes responsible for the biodeterioration of façade finishes and the effects this has on the buildings and public health in the hot-humid tropics of Enugu, Southeast Nigeria.
How are economic policy uncertainty shocks transmitted to capital structure? Chinese evidence
Authors: Li Xiao-Ming , Qiu Mei
Published: September 2022

Purpose

The purpose of this paper is to investigate the mechanism of transmitting economic policy uncertainty (EPU) shocks to capital structure.

Design/methodology/approach

The authors adopt a novel approach that bridges the asset pricing implications of EPU and the debt-financing decisions of Chinese firms by introducing a variable “policy-risk-induced equity return” (PRER). PRER is the product of the EPU beta and the EPU shock. Differentiating firms as per the signs of the EPU beta helps to shed light on the deep questions of whether their respective leverage targets and speeds of adjustment are different and how the targets and speeds are determined.

Findings

The empirical evidence shows that it is the equity market that channels EPU shocks to capital structure through PRER in China. Firms with positive (negative) EPU betas have PRER impact negatively (positively) the leverage target, conforming to the market-timing theory. EPU and non-policy uncertainty shocks cause the speed of adjustment to change over time. Overall, the intertemporal relation between EPU and leverage is negative. These results are robust to alternative leverage measures and after controlling for non-policy uncertainty shocks and conventional firm characteristics and have implications for academic research, policymaking, market stability, and corporate financing.

Originality/value

This study is the first to probe for, and provide insights into, the underlying reason why EPU impacts capital structure by connecting asset pricing to corporate financing for a large sample of Chinese publicly traded firms.
Occupational segregation, microaggression, social exclusion, and turnover intentions: mediating and moderating impact of social invisibility and felt obligation
Authors: Batool Sadia , Kashif Muhammad
Published: September 2022

Purpose

This study investigates occupational segregation, microaggression, and social exclusion as antecedents of social invisibility to predict employee intentions to leave. Furthermore, the authors question whether felt obligation moderates the relationship between social invisibility and intentions to leave. Finally, researchers explore various forms of occupational segregation, miscoaggression, and social exclusion from employee's perspective.

Design/methodology/approach

Two studies are conducted. Study 1 is quantitative where the data were collected from 273 nurses employed in various hospitals in Pakistan. Study 2 is qualitative where twelve confirmatory interviews were conducted to enrich our contextual understanding of the proposed relationships. The quantitative data are analyzed using partial least square methods via SmartPLS. The qualitative data analysis is based on a content analysis of interviews.

Findings

Surprisingly, occupational segregation does not predict social invisibility. Moreover, the relationship between occupational segregation and intentions to leave is not mediated via social invisibility. The issues such as social hierarchy and high power distance are reflected via the findings of the qualitative study.

Practical implications

The results provide insightful strategies to counter feelings of social invisibility among individuals performing those jobs which are considered stigmatized occupations.

Originality/value

This study uniquely presents three antecedents of social invisibility, its mediating role, and the moderation of felt obligation between social invisibility and intentions to leave.
Forecasting office rents with ensemble models – the case for European real estate markets
Authors: von Ahlefeldt-Dehn Benedict , Cajias Marcelo , Schäfers Wolfgang
Published: September 2022

Purpose

Commercial real estate and office rental values, in particular, have long been the focus of research. Several forecasting frameworks for office rental values in multivariate and univariate fashions have been proposed. Recent developments in time series forecasting using machine learning and deep learning methods offer an opportunity to update traditional univariate forecasting frameworks.

Design/methodology/approach

With the aim to extend research on univariate rent forecasting a hybrid methodology combining both ARIMA and a neural network model is proposed to exploit the unique strengths of both methods in linear and nonlinear modelling. N-BEATS, a deep learning algorithm that has demonstrated state-of-the-art forecasting performance in major forecasting competitions, are explained. With the ARIMA model, it is jointly applied to the office rental dataset to produce forecasts for four-quarters ahead.

Findings

When the approach is applied to a dataset of 21 major European office cities, the results show that the ensemble model can be an effective approach to improve the prediction accuracy achieved by each of the models used separately.

Practical implications

Real estate forecasting is essential for assessing the value of managing portfolios and for evaluating investment strategies. The approach applied in this paper confirms the heterogeneity of real estate markets. The application of mixed modelling via linear and nonlinear methods decreases the uncertainty of abrupt changes in rents.

Originality/value

To the best of the authors' knowledge, no such application of a hybrid model updating classical statistical forecasting with a deep learning neural network approach in the field of commercial real estate rent forecasting has been undertaken.