bluuebunny/crossref_metadata_2025 huggingface dataset:
INVESTIGATING LOCAL RECURRENCE IN SECONDARY BRAIN TUMOURS
Authors: Suppree Joshua , Jenkinson Michael D , Zakaria Rasheed
Published: September 2023

AIMS

Brain metastases result in considerable morbidity and mortality. Modern treatment strategies are increasingly omitting radiation therapy after surgical resection of these tumours. We investigated the rate of local recurrence in patients who had undergone surgery for brain metastasis in a single-institution study and compared it to the literature through a comprehensive meta-analysis.

METHOD

Patients undergoing surgery for a brain metastasis were identified and their records reviewed. Data on treatment and outcome was extracted and analysed. A systematic-review and meta-analysis, registered in PROSPERO (CRD42023391637), was conducted following the PRISMA statement.

RESULTS

The single-institution study comprised 358 cases, 40% (n=142) male and 60% (n=216) being female with a median age at surgery of 60 years (range 23-85 years). The most frequent primary cancer was lung cancer affecting 35% (n=126), followed by breast cancer (24%, n=87) and malignant melanoma (13%, n=47). Among the cases 142 underwent surgery without any adjuvant radiation. The median freedom from local recurrence at 12-months for this population was 38.3% (95% CI 13.4, 44.6). The meta-analysis encompassed three studies, with a total of 170 cases. Freedom from local recurrence at 12-months was found to be 42.4% (95% CI 34.9 - 50.1) following surgery alone.

CONCLUSIONS

We define for the first time the rates of local recurrence following surgery alone for brain metastases with a large single-centre series and a meta-analysis. As radiation is increasingly being omitted in these cases, caution should be exercised, and more investigation of the factors associated with local recurrence after surgery and how they be modified are required.
INVESTIGATING NOTCH1 PATHWAY COMPONENTS IN HISTONE 3.3 MUTANT PAEDIATRIC HIGH-GRADE GLIOMA
Authors: Emayakumaran Emayanthi , Lourdusamy Anbarasu , Layfield Robert , Haque Farhana
Published: September 2023

AIMS

High-grade gliomas (HGG) in adults and children (paediatric high-grade glioma, pHGG) differ in molecular characteristics, despite having the same morphological features. Although pHGG has a low incidence, it contributes to 40% of all brain tumour death in childhood. Histone 3 (H3) mutation is a unique feature of pHGG. The understanding the pathophysiology of these tumour are important to develop more targeted therapy for these tumours.

Our previous research has identified, increased activation of the Notch1 pathway in H3 mutated tumours. We have now explored the relationship between the Notch1 pathway components to H3 mutated pHGG. We hypothesised that The Notch1 pathway components (NICD1, HES1, HES5) are dysregulated in the Histone 3 mutant tumours in comparison to H3 wild type tumours.

METHOD

Protein expression analyses, immunofluorescence and microscopy and western blot experiments were per- formed, to assess the localization and expression of Notch1 pathway components (NICD1, HES1, HES5), using cultures H3.3 wildtype and H3.3 mutant cell lines.

RESULTS

The results show that Notch1 pathway expression differ between H3 mutant and H3 wild type tumours.

CONCLUSIONS

These results suggest that components of Notch1 pathway (HES1/HES5) are dysregulated, which may be driving tumour growth in this H3 mutated tumour. Therefore, we can explore Notch1 Pathway components as targeted therapeutic options.
PROCARBAZINE, LOMUSTINE, VINCRISTINE FOR THE SECOND LINE TREATMENT OF GLIOBLASTOMA MULTIFORME
Authors: McCormick Cecilia , Gkogkou Pinelopi , Ho Andrew
Published: September 2023

AIMS

Most patients with glioblastoma recur despite surgery and post-operative chemoradiation. The optimal second line chemotherapy regime is not known. The aim of this study was to evaluate PCV chemotherapy given as second line treatment for glioblastoma.

METHOD

Data was collected for all patients with glioblastoma treated with second line PCV between 2009 and 2021 at the Norfolk and Norwich University Hospital. All underwent surgical resection either complete or incomplete resection followed by adjuvant radiotherapy and chemotherapy according to the Stupp or Perry A protocol. All received palliative PCV chemotherapy at recurrence. The Response Assessment in Neuro-Oncology (RANO) criteria were used to assess response to palliative PCV chemotherapy. Patient and disease related characteristics were described. Disease free survival from recurrence to death and survival outcomes were estimated using Kaplan-Meir method.

RESULTS

70 patients were evaluated. Overall survival from surgery to death was 290 days (95%CI 245 to 318)

Survival from disease progression to death was 182 days (95%CI 131 to 218). Subgroup analysis was performed for patients <65years and >65years. For patients <65 years N=51, median overall survival was 199 days (95%CI 142 to 353) p value 0.1246. For those >65 years N=16, median overall survival was 130.5 days (95%CI 93 to 227)

CONCLUSIONS

Using PCV as a second line chemotherapy for patients with glioblastoma is a reasonable approach. It is well tolerated and provides benefit for patients <65 years as well as older patients.
IN VITRO MODELLING OF CROSSTALK BETWEEN PAEDIATRIC CEREBELLAR TUMOURS AND HEALTHY BRAIN TISSUE IN THE POST-SURGICAL MICROENVIRONMENT
Authors: Porter Harry , McCrorie Phoebe , Moloney Cara , Collier Pamela , Croxall Nicola , Onion David , Kotowska Anna , Scurr David , Diksin Mohammed , Grundy Richard , Rahman Ruman
Published: September 2023

AIMS

Atypical Teratoid Rhabdoid Tumours (ATRT) and Medulloblastoma are embryonal brain tumours arising in the cerebellum. Many in vitro models of paediatric brain tumours fail to recapitulate key pathophysiological characteristics. We aim to address this gap by developing a bespoke model incorporating cellular and acellular aspects of the TME.

METHOD

Cerebellar tissue from a healthy human autopsy donor brain was decellularized to form cerebellar ECM and incorporated into a “blank slate” hydrogel. Spheroid-forming multi-well plates were coated with the hydrogel and used to culture patient-derived Medulloblastoma and ATRT cells in co-culture with primary human cerebellar astrocytes.

RESULTS

Tissue decellularization and retention of ECM components was demonstrated using colorimetric assays and Orbitrap Secondary Ion Mass Spectrometry. Biocompatibility of the ECM hydrogel was shown in 2D and 3D culture conditions using the CellTiter-Glo® 3D cell viability assay. Furthermore, the size and morphology of spheroids grown on the hydrogel was characterised using a high-throughput imaging and analysis methodology. Cell lines were labelled to facilitate discrimination between tumour cells and astrocytes. Optical sections of co-culture spheroids generated using confocal microscopy showed cell-cell contact between tumour cells and astrocytes. Finally, co-culture spheroids were separated by fluorescence activated cell sorting to facilitate downstream analyses on individual cell types.

CONCLUSIONS

This work presents a highly characterised model of medulloblastoma and ATRT interactions with healthy brain tissue, mimicking the immediate post-surgical microenvironment. Future work will utilise transcriptomics to assess the tumour-astrocyte crosstalk modelled using this system.
DIFFERENTIAL CELL SURFACE PROTEOMICS OF FLOTILLIN-1, HMGB1 AND AMINOPEPTIDASE IN H3 MUTATED PAEDIATRIC HIGH-GRADE GLIOMA
Authors: Walugembe Chloe , Litchfield-Williams Matthew , Snary Anya , Layfield Robert , Haque Farhana
Published: September 2023

AIMS

High-grade gliomas (HGG) are the deadliest central nervous system tumour in children. Despite this, treatment options remain elusive, leaving children with a dismal prognosis. Histone H3.3 mutations, K27M and G34V/R have been identified as the two most common recurrent somatic mutations in paediatric HGG (pHGG). These mutations are present in 50% of pHGG compared to only 1% in adults.

Our previous research on cell membrane protein analyses have identified different signature of unique and common cell membrane proteins in H3-G34R/V mutated pHGG, in comparison to H3 wild type tumour. Among these we have identified flotillin-1, HMGB1 and aminopeptidase N. Flotillin-1 promotes numerous malignancies, High mobility group box 1(HMGB1) functions as an oncogene and aminopeptidase N is a cell surface metallo- protease involved in tumour progression. We have now verified the expression and localization of these cell surface proteins in H3 mutated and wildtype tumour, in order to target them for developing novel therapeutics.

METHOD

Cell membrane proteomics were further verified though mass-spectrometric data analyses. Expression and localization of flotillin-1, HMGB1 and Aminopeptidase in H3.3 mutated pHGG cell lines in comparison to H3 wildtype glioma were analysed, using different protein expression assays including immunofluorescence microscopy and western blot assays.

RESULTS

Experimental analyses showed differential protein expression and localization of Flotillin-1, HMGB1 and Aminopeptidase and verified the mass-spectrometric proteomic data in H3-G34V pHGG, in comparison to wild- type pHGG.

CONCLUSIONS

This new knowledge will help us utilise Flotillin-1, HMGB1 and Aminopeptidase N, as potential therapeutic targets for these unique H3 mutated children’s brain tumours.
ADULT HISTONE G34 MUTANT GLIOMAS - A SINGLE CENTRE EXPERIENCE OVER 10 YEARS
Authors: Obrocki Ruth , Merve Ashirwad , Rees Jeremy
Published: September 2023

AIMS

Histone G-34-mutant (H3 G34) gliomas are rare, aggressive infiltrating tumours of the cerebral hemispheres and are classified as WHO grade 4 paediatric type diffuse high-grade glioma. They most commonly affect children and adolescents.

We describe the clinicopathological characteristics of adult H3 G34-mutant gliomas seen at the National Hospital for Neurology and Neurosurgery over the last 10 years.

METHOD

We retrospectively analyzed clinic radiological data on all cases identified from the neuropathology database. Data were extracted on patient demographics, clinical and radiological features and outcome.

RESULTS

Six patients (2 male, 4 female) were identified, The median age of onset was 26 years (range 17-38 years). One patient presented with a Motor Neurone Disease type syndrome (progressive asymmetric spastic tetraparesis and bulbar symptoms), two with cognitive decline and three with symptoms of raised intracranial pressure. All tumours were supratentorial - 2 patients had mass lesions typical of a high-grade glioma, 1 patient had imaging features consistent with an intraventricular ependymoma. 3 patients had imaging findings that suggested a non-tumour diagnosis with extensive white matter disease more in keeping with an inflammatory demyelinating process or a leucodystrophy.

The median overall survival was 23 Months (range 10 - 68 months).

CONCLUSIONS

Adult Histone G34-mutant gliomas have a variable presentation and are associated with a prognosis similar to other high-grade gliomas. The diagnosis should be considered in the differential of patients presenting with a predominantly white matter disorder. Multi-centre studies are needed to better delineate the phenotype and prognostic features.
MATHEMATICAL MODELLING OF SURVIVAL IN LOW GRADE GLIOMAS AT MALIGNANT TRANSFORMATION
Authors: Tan Lily , Ruffle James , Rees Jeremy , Kosmin Michael , Nachev Parahkev , Hyare Harpreet
Published: September 2023

AIMS

Low grade gliomas (LGG) represent 14.6% of gliomas and may remain stable years after initial diagnosis. MRI features suggesting malignant transformation (MT) include enlargement of non-enhancing areas and increasing enhancement but have low specificity. We report the first stages of a deep learning model to predict survival using radiomic feature extraction at MT, clinical and molecular genetics.

METHOD

Retrospective analysis of all LGGs treated at our institution (2005 - 2020) with histology, molecular genetics and MRIs. 766 patients: 457 IDH mutant astrocytomas, 251 IDH mutant 1p19q co-deleted oligodendrogliomas and 58 other gliomas; 398 male, 368 female; mean age 51 years; range 16-89. MRIs underwent in-house tumour segmentation pipeline with radiomic feature extraction of whole tumour (wt), enhancing (enh), non-enhancing (ne) component and oedema components.

RESULTS

At MT, mean wt volume was 36404mm3 (SD 37213mm3) with mean 2D-diameter of 75.90mm (SD 27.23mm). Mean tissue compartmental volumes: enh 9539mm3 (SD 17578mm3), ne 26865mm3 (SD 33796mm3), and oedema 61067mm3 (SD 61535 mm3). 92 lesions contained no post-contrast enhancing tissue. Lesions were more commonly frontal or temporally based, with relative sparing of parietal and occipital lobes. No predilection for left or right hemisphere.

CONCLUSIONS

Majority of LGGs demonstrate contrast enhancing lesions at MT in a frontal or temporal spatial distribution with no hemispheric predilection. We plan to extract the MRI features at MT to build a survival model with clinical, treatment and molecular genetic data. Defining the radiological features at MT would enable prognostication and support clinical decision-making in this patient group.
INTEGRATIVE ANALYSIS OF DIFFERENTIALLY REGULATED PROTEINS IN MENINGIOMA
Authors: Shah Maryam , Banton Matthew , Adams Claire , De Assis Leandro , Sharma Vikram , Hanemann Oliver
Published: September 2023

AIMS

Meningiomas are common primary intracranial tumours that arise from meninges. loss of chromosome 22q is common genetic event observed in meningiomas. About 50% of meningiomas harbour mutations in NF2 gene that resides on chromosome 22. Moreover, frequent mutations have been observed in AKT1, KLF4, TRAF7, and SMO genes. Meningiomas are divided into different genomic subgroups that express unique proteomic profiles. This study aims to investigate genomic background of meningioma and to determine the impact of mutations on underlying protein expression to identify druggable targets.

METHOD

Total 96 meningioma samples were sequenced using Illumina TruSight Oncology 500 panel. The raw sequence data was analyzed using TSO500 App. The variant data was annotated using Cancer Genome Interpreter and ANNOVAR. Clinical enrichment analysis was performed to investigate common pathways. Genomic data was correlated with LC-MS based proteomic data to determine variants effect on downstream processes.

RESULTS

Results showed an average of 1083 total and 7 driver mutations per sample. NF2 gene was found among highly mutated genes in tumour samples. Almost all NF2 mutations were frameshift, splice site and nonsense mutations, previously reported to be associated with high rate of multiple and recurring meningiomas. Additionally, driver mutations were identified in known meningioma genes including AKT1, KLF4, and TRAF7 along with previously unpublished mutations in ERBB2, MET, ARID5B, etc. The results correlate with tumour location, grade, and histopathological subtype.

CONCLUSIONS

The study identified common as well as unique driver mutations in meningioma samples. After functional validation, novel driver mutations could further enhance personalized treatment for meningioma patients.
TITLE THE TEENAGE AND YOUNG ADULT (TYA) POPULATION (16-24YO) BENEfiT FROM HAVING SPECIALIST NURSE INPUT
Authors: Hedges Sarah , La Jessica , Robinson Charlotte , Hurwitz Victoria , Kostick Ellie , Suarez Aeron , Harding Nicola , Fukuthi Renata , Brazil Lucy , Cikurel Katia , Al-Salihi Omar , Swampillai Angela , Chia Kazumi , Manik Vishal , Bhangoo Ranjeev , Ashkan Keyoumars , Lavrador Jose Pedro , Vergani Francesco , Gullan Richard , Zebian Bassel , Bleil Cristina
Published: September 2023

AIMS

The aim of this review is to analyse the need for a specialist nurse role for the TYA patients. Having a new dedicated TYA developmental role implemented can help by identifying areas for improvement from the wider team to ensure optimal support for patient group.

METHOD

Clinic attendance over a 1-year period has been measured. Looking specifically at patients who did not attend (DNA) appointments in a monthly TYA joint surgical and oncology clinic. We have evidence engaging this age group with the creation of a nurse led weekly telephone clinic for TYA patients and have looked at the trajectory of attendees throughout the year.

RESULTS

To date, nurse led clinic has had 107 individual bookings between August 2022 and February 2023. This is a devoted telephone clinic to provide holistic care.

CONCLUSIONS

There were 107 nurse lead telephone clinic appointments that were booked and attended by this patient group over 6-month period. This was protected time for which the nurse specialist was able to explore patients individual care needs in a holistic way. Figures for holistic needs assessment (eHNA) are yet to be collated; but the TYA group are now routinely offered eHNA to ensure a holistic care approach and support to this vulnerable patient group.
AN AUDIT OF STEROID-INDUCED DIABETES IN PRIMARY BRAIN TUMOUR PATIENTS
Authors: Bog Ji Yun , Lorimer Cressida , Brock Juliet , Chandy Edward
Published: September 2023

AIMS

Dexamethasone is an effective and commonly used treatment in patients with gliomas. However, it can also cause several metabolic side effects, including steroid-induced diabetes mellitus (SIDM), of which prevalence is estimated at 11-56%. We aimed to assess prevalence of SIDM in our local brain tumour population and audited adherence to recently published national guidance for monitoring and management of SIDM.

METHOD

Retrospective data review of all new primary malignant brain tumour patients seen in clinic over 12 months to assess local prevalence. Patients’ notes audited for 2 months pre- and post-adoption within the department of national guidelines focussing on how to screen and monitor for diabetes when initiating high dose steroids.

RESULTS

71 new patients seen over 12 months. 66 patients with high grade and 5 with low grade gliomas. 82% were on steroids at first oncological visit. 14% known diabetic or pre-diabetic. 7% subsequently developed SIDM.

19 patient notes audited over 2 months prior to intervention (Group 1) and 11 post intervention (Group 2). All patients were taking dexamethasone. 40% of Group 1 and 36% of Group 2 had neither HbA1c nor lab glucose checked at baseline. 1 patient in Group 1 developed SIDM.

CONCLUSIONS

Diabetes mellitus in cancer patients increases risk of infections, cardiovascular comorbidities, and can reduce effcacy of treatment, leading to preventable admissions and decreased survival rates. Prevalence of SIDM in our local population is comparable to published data. Adoption of published guidance improved baseline monitoring but needs to be embedded within acute oncology pathways across the Trust.
THE KYNURENINE PATHWAY AND ITS ROLE IN GLIOBLASTOMA CELL MIGRATION
Authors: Sirnikova Diana , Reynisson Johannes , Brüning-Richardson Anke , Kirby Catherine
Published: September 2023

AIMS

The kynurenine (Kyn) pathway plays an important role in the pathogenesis of many cancers including glioblastomas (GBMs). The enzymes, indoleamine-2,3-dioxygenase (IDO1) and tryptophan-2,3-dioxygenase (TDO2), regulate the first and rate-limiting step resulting in the formation of N-formyl-kynurenine, which is then readily converted into Kyn by kynurenine formaldehyde. Cancers expressing the IDO1 and TDO2 enzymes can produce immunosuppressive tryptophan metabolites that compromise the host immune system leading to poor patient prognosis. The inhibitors TD12, TD18 and TD34 were recently developed due to the lack of TDO2 and IDO1/TDO2 inhibitors, of which TD34 can block both IDO1 and TDO2 activity. Here, we investigated the ability of these novel inhibitors to also target cell migration in GBM as part of our ongoing research interest in this area.

METHOD

Two established brain tumour cell lines, U87 and U251 and one patient-derived cell line, E55, were used to determine IC50 values and anti-migratory concentrations by MTT for application in 2D and 3D migration/invasion assays.

RESULTS

Cell migration in all cell lines was significantly reduced in the presence of the TD12, TD18 and TD34 inhibitors. E55 appeared to be 100-fold more sensitive to drug activity; immunofluorescence analysis indicates changes in the actin cytoskeleton and cell adhesion

CONCLUSIONS

Initial results suggest that TDO2 and the IDO1 enzymes play also a role in cell migration in GBM and provide further evidence for the involvement of the Kyn pathway in the pathology of GBMs. This also supports the application of inhibitors targeting TDO2 and IDO1 as novel complementary treatment options in GBM.
Thermal annealing promoted room temperature phosphorescence: motion models and internal mechanism
Authors: Gao Yan , Lu Jie , Liao Qiuyan , Li Shuhui , Li Qianqian , Li Zhen
Published: September 2023

Thermal annealing has been proven to be an efficient method to optimize the device performance of organic and polymeric opto-electronic materials. However, no detailed information of aggregate structures was obtained for a deeper understanding of what happens during thermal annealing. Herein, through modulation of molecular configurations by tunable linkage positions, and the amplified amplitudes of molecular motions by incorporation of additional methylene units, accurate changes of aggregated structures upon thermal annealing have been achieved, accompanying with the ‘turn-on’ room temperature phosphorescence (RTP) response by about 4800- and 177-fold increase of lifetimes. The stretching and swing motion models have been proposed, which afforded an efficient way to investigate the science of dynamic aggregation in depth.
Immune-Related Adverse Event Likelihood Score Identifies “Pure” IRAEs Strongly Associated With Outcome in a Phase I-II Trial Population
Authors: Mazzarella Luca , Giugliano Federica , Nicolo Eleonora , Esposito Angela , Crimini Edoardo , Tini Giulia , Uliano Jacopo , Corti Chiara , D’Amico Paolo , Aliaga Pamela Trillo , Valenza Carmine , Repetto Matteo , Antonarelli Gabriele , Ascione Liliana , Vivanet Grazia , Berton Giachetti Pierpaolo , Minchella Ida , Belli Carmen , Locatelli Marzia , Criscitiello Carmen , Curigliano Giuseppe
Published: September 2023

Background

Immune-related adverse events (IRAE) pose a significant diagnostic and therapeutic challenge in patients treated with immune-oncology (IO) drugs. IRAEs have been suggested to correlate with better outcome, but studies are conflicting. Estimating the true incidence of IRAEs is particularly difficult in the early phase I/II trial setting. A key issue is the lack of IRAE diagnostic criteria, necessary to discriminate “pure” IRAEs from other treatment-related adverse events not sustained by an autoimmune process.

Methods

In patients treated with immune-oncology (IO) drugs in phases I-II trials at our institute, we identified high confidence (HC) or low confidence (LC) IRAEs by clinical consensus. We empirically developed an IRAE likelihood score (ILS) based on commonly available clinical data. Correlation with outcome was explored by multivariate Cox analysis. To mitigate immortal time-bias, analyses were conducted (1) at 2-month landmark and (2) modeling IRAEs as time-dependent covariate.

Results

Among 202 IO-treated patients, 29.2% developed >1 treatment-related adverse events (TRAE). Based on ILS >5, we classified patients in no IRAE (n = 143), HC IRAE (n = 24), or LC IRAE (n = 35). hazard ratios (HR) for HC were significantly lower than LC patients (HR for PFS ranging 0.24-0.44, for OS 0.18-0.23, all P < .01).

Conclusion

ILS provides a simple system to identify bona fide IRAEs, pruning for other treatment-related events likely due to different pathophysiology. Applying stringent criteria leads to lower and more reliable estimates of IRAE incidence and identifies events with significant impact on survival.
Telomere length links with physiological phenotype and breeding patterns in a long-lived seabird
Authors: Guillen-Parra Mauricio , Velando Alberto , Barcenas-Flores Rocio , Nicolás-Toledo Leticia , Torres Roxana
Published: September 2023

Telomere length (TL) is known to covary with a suite of physiological traits involved in energy balances that may influence breeding success. Thus, TL may be an indicator of individual quality, influencing mate choice and breeding strategies. In the Brown Booby (Sula leucogaster), a long-lived seabird, we investigated in a total of 72 pairs whether TL may indicate the individual physiological phenotype by examining how it relates to mitochondrial DNA copy number (mtDNAcn) and corticosterone (CORT) levels. Then, we tested if TL is associated with mating patterns by looking for covariation with skin coloration (a condition-dependent sexual trait), whether there is assortative mating by TL, and if the degree of TL similarity between partners influences an individual’s likelihood of changing mates between reproductive seasons. Because environmental conditions can have important effects on the condition and reproductive strategies of individuals, the study was performed in 2 colonies with contrasting breeding conditions. We found that TL was positively related to mtDNAcn (but not CORT levels), suggesting that individuals with shorter telomeres may have a reduced mitochondrial density. TL was reflected in sexual coloration, but only in the colony with good breeding conditions. There was positive assortative mating by TL; however, the degree of assortative mating was unrelated to the probability of mate change, which greatly varied between the 2 colonies. Our results suggest that TL is associated with the physiological phenotype of individuals and their breeding patterns. Importantly, contrasting environmental conditions influenced the link between TL and sexual coloration and the propensity of individuals to change mate, highlighting the importance of environmental variation on mating patterns.
Gender Gaps in Political Ambition on Different Levels of Policy-Making
Authors: Devroe Robin , Coffé Hilde , Vandeleene Audrey , Wauters Bram
Published: September 2023

Women consistently report lower levels of nascent political ambition than men. In this study, we investigate whether these gender differences occur to the same extent across local, national and European levels of policy-making. Using original data collected among a representative sample of young Flemish citizens aged between 18 and 35 (N = 1000), our descriptive results demonstrate a significant gender gap across all levels of policy-making, though the gap is slightly smaller at the local level. Stacked multivariate analyses confirm women’s lower levels of political ambition and show that the gender gap is significantly smaller at the local level compared with the European (but not the national) level, pointing to women’s lower levels of ambition for the European level.
Are Nonprobability Surveys Fit for Purpose?
Authors: Jerit Jennifer , Barabas Jason
Published: September 2023

Social scientists employ survey methods to explore the contours of human behavior. Today there are more opportunities to collect survey data than at any time in recent history. Yet sample quality varies dramatically due in part to the availability of nonprobability samples (NPSs) from commercial survey organizations. While these kinds of surveys have advantages in terms of cost and accessibility, the proprietary nature of the data can be problematic. In this synthesis, we describe situations in which researchers typically employ NPSs and consider whether these data are fit for purpose. Next, we discuss use cases that are not widespread but may be appropriate for these data. We conclude that potential utility of NPSs will remain out of reach unless scholars confront the tension between the operation of online survey organizations and the goals of transparent research.
Issues, Groups, or Idiots? Comparing Theories of Partisan Stereotypes
Authors: Myers C Daniel
Published: September 2023

When individuals picture the two parties, what do they think of? Given the dominant understanding of partisanship as a social identity, understanding the content of these mental images—individuals’ stereotypes of the two parties—is essential, as stereotypes play an important role in how identity affects attitudes and behaviors, perceptions of others, and inter-group relations. The existing literature offers three answers to this question: one that claims that people picture the two parties in terms of their constituent social groups, a second that claims that people picture the two parties in terms of policy positions, and a third that claims that people view the two parties in terms of individual traits they associate with partisans. While not mutually exclusive, these theories have different implications for the effects of partisanship and the roots of partisan animosity. This paper adjudicates between these theories by employing a new method that measures stereotype content at the collective and individual level using a conjoint experiment. An important advantage of the conjoint measure is that it allows for the direct comparison of the importance of different attributes, and different kinds of attributes, to the stereotype. Using a pre-registered 2,909-person survey, I evaluate the relative importance of issues, groups, and traits to stereotypes of partisans. I find strong evidence that issue positions and ideological labels are the central elements of partisan stereotypes. I also find that individuals who hold issue- or ideology-based stereotypes are more affectively polarized than those whose stereotypes are rooted in groups or traits.
Harmonic And Neutral Spherical Elastic Inhomogeneities with A Functionally Graded Interphase Layer
Authors: Wang Xu , Schiavone Peter
Published: September 2023

We study the elastic field in a three-phase composite composed of an internal spherical homogeneous elastic inhomogeneity, an intermediate functionally graded interphase layer and an outer unbounded homogeneous elastic matrix subjected to an arbitrary uniform remote loading. The shear modulus of the interphase layer obeys a power law distribution along the radial direction. We accomplish the design of harmonic and neutral spherical elastic inhomogeneities. Specifically, the shear modulus of the matrix can be judiciously chosen in such a way that the insertion of the harmonic spherical inhomogeneity does not disturb the original constant mean stress in the surrounding matrix. The shear modulus of the matrix and relative thickness of the interphase can also be suitably chosen such that the insertion of the neutral spherical inhomogeneity does not disturb the original uniform deviatoric stresses in the surrounding matrix.
Influence of sex hormone use on sleep architecture in a transgender cohort
Authors: Morssinkhof Margot W L , van der Werf Ysbrand D , van den Heuvel Odile A , van den Ende Daan A , van der Tuuk Karin , den Heijer Martin , Broekman Birit F P
Published: September 2023

Study Objectives

Sex differences in sleep architecture are well-documented, with females experiencing longer total sleep time, more slow wave sleep (SWS), and shorter Rapid Eye Movement (REM) sleep duration than males. Although studies imply that sex hormones could affect sleep, research on exogenous sex hormones on sleep architecture is still inconclusive. This study examined sleep architecture changes in transgender individuals after 3 months of gender-affirming hormone therapy (GAHT).

Methods

We assessed sleep architecture in 73 transgender individuals: 38 transmasculine participants who started using testosterone and 35 transfeminine participants who started using estrogens and antiandrogens. Sleep architecture was measured before GAHT and after 3 months of GAHT for 7 nights using an ambulatory single-electrode sleep EEG device. Changes in sleep architecture were analyzed using linear mixed models, and non-normally distributed outcomes were log-transformed and reported as percentages.

Results

In transmasculine participants, SWS decreased by 7 minutes (95% CI: −12; −3) and 1.7% (95% CI: −3%; −0.5%), REM sleep latency decreased by 39% (95% CI: −52%; −22%) and REM sleep duration increased by 17 minutes (95% CI: 7; 26) after 3 months of GAHT. In transfeminine participants, sleep architecture showed no significant changes after 3 months of GAHT.

Conclusions

Sleep architecture changes after 3 months of masculinizing GAHT in line with sleep in cisgender males, while it shows no changes after feminizing GAHT. The sex-specific nature of these changes raises new questions about sex hormones and sleep. Future research should focus on studying possible underlying neural mechanisms and clinical consequences of these changes.
Clinical profile of infants with late onset sepsis admitted in a North East Indian tertiary care center: insights into the uncharted
Authors: Niranjana Sugunan , Singh Chongtham Shyamsunder , Devi Khuraijam Ranjana , Singh O Okendrajit , Smilie Chabungbam , Nandeibam Sareet Kumari
Published: September 2023

Objectives

To assess the clinical profile of infants with late onset sepsis admitted in a tertiary care hospital in North-East India.

Methods

Prospective observational study was carried out in Department of Paediatrics, Regional Institute of Medical Sciences hospital during a period of 2 years (September 2019–August 2021).

Results

A total of 109 patients were included in the study, of which 80 were community-acquired and 29 infants were hospital-acquired cases of late onset sepsis (LOS). The major risk factors were low socioeconomic status, prematurity, low birth weight, a history of intervention (mechanical ventilation, umbilical venous catheter, total parenteral nutrition, resuscitation) and lack of exclusive breastfeeding. The most common presenting features were decreased feeding, lethargy and respiratory distress. Blood cultures were positive in 33% of patients. Klebsiella was the most common hospital-acquired pathogen while Escherichia coli was the most common isolate in community-acquired cases. Thrombocytopenia was the most common complication. The in-hospital mortality rate was 13.7%.

Conclusion

Low socioeconomic status, low birth weight, prematurity, invasive interventions and lack of exclusive breastfeeding are the major risk factors of LOS. The clinical signs and symptoms are varied and subtle. The mean C-reactive protein in the hospital-acquired group was significantly higher as compared to the community-acquired group. There is substantial morbidity and mortality, resulting in an increased toll on resources, therefore, an aggressive preventive and treatment approach is recommended for late onset sepsis.
Top of the food chains: an ecological network of the marine Paja Formation biota from the Early Cretaceous of Colombia reveals the highest trophic levels ever estimated
Authors: Cortés Dirley , Larsson Hans C E
Published: September 2023

The Mesozoic Marine Revolution restructured the world’s ocean biodiversity into the complex marine ecosystems of today. This revolution began during the Triassic but the origin of this complexity is poorly understood due to a lack of detailed ecosystem reconstructions throughout time. We present the first site-specific ecological network for a marine Mesozoic fauna based on the Early Cretaceous Paja Formation biota of Colombia that preserves numerous, large-bodied, predatory marine reptiles. The trophic food-web was quantitatively reconstructed based on inferred trophic interactions of marine producers, consumers, and large apex predators. Compared to well-studied Caribbean reef ecosystem networks, the Paja biota network is missing a great proportion of benthic invertebrates and fishes, despite its rich higher trophic levels. We hypothesize that the ammonites from the Paja biota either mirrored the diversity represented by some fishes today or established a novel trophic unit with no living analogue. Recalibrating the Paja biota network to trophic analogues in the Caribbean, such as sea turtles, estimates that the largest Paja marine reptile hyper-apex predators occupied trophic levels a full tier higher than any extant marine apex predator. The Paja biota network is a starting point to tracing the evolution of marine ecosystems across the Mesozoic Marine Revolution.
Characteristics and prognostic factors of adult patients with osteosarcoma from the SEER database
Authors: Deng Guanghua , Chen Pingbo
Published: September 2023

Osteosarcoma is the most common bone malignancy. There are many studies on the prognostic factors of children and adolescents, but the characteristics and prognostic factors of adult osteosarcoma are rarely studied. The aim of this study was to construct a nomogram for predicting the prognosis of adult osteosarcoma. Information on all osteosarcoma patients aged ≥ 18 years from 2004 to 2015 was downloaded from the surveillance, epidemiology and end results database. A total of 70% of the patients were included in the training set and 30% of the patients were included in the validation set. Univariate log-rank analysis and multivariate cox regression analysis were used to screen independent risk factors affecting the prognosis of adult osteosarcoma. These risk factors were used to construct a nomogram to predict 3-year and 5-year prognosis in adult osteosarcoma. Multivariate cox regression analysis yielded 6 clinicopathological features (age, primary site, tumor size, grade, American Joint Committee on Cancer stage, and surgery) for the prognosis of adult osteosarcoma patients in the training cohort. A nomogram was constructed based on these predictors to assess the prognosis of adult patients with osteosarcoma. Concordance index, receiver operating characteristic and calibration curves analyses also showed satisfactory performance of the nomogram in predicting prognosis. The constructed nomogram is a helpful tool for exactly predicting the prognosis of adult patients with osteosarcoma, which could enable patients to be more accurately managed in clinical practice.
Analysis of the improvement in monocular amblyopia visual acuity caused by the changes in non-amblyopia visual acuity in 74 adults
Authors: Guo Yong , Yan Hong , Guo Chenjun , Zhang Dan , Wang Jue , Li Yan , Yang Yuhuan
Published: September 2023

To observe the clinical phenomenon of amblyopia vision improvement in patients with monocular amblyopia over 18 years old after non-amblyopia diseases, analyze the conditions and causes of vision improvement, explore the plasticity of the adult optic nerve, and provide a clinical basis for the treatment of adult amblyopia. A total of 74 patients with monocular amblyopia combined with non-amblyopia visual acuity decline from 2018 to 2021 were collected. The patient’s age, initial best-corrected visual acuity (BCVA), pattern visual evoked potential examination results, and visual acuity regression were recorded. The BCVA of amblyopia was recorded every 3 months using an early treatment of diabetic retinopathy study visual acuity chart. In the 3rd month, BCVA increased by 16.2%, reaching 98% in the 9th month and 100% in the 12th months. According to the age of patients, the group aged 18 to 35 years was better than the group aged 35 to 60 years, whereas the group aged 35 to 60 years was better than the group aged over 60 years (P < .05). According to the comparison of initial visual acuity, the BCVA of the < 5 letter group was lower than that of the other 2 groups (P < .05). According to the pattern visual evoked potential results, the peak time of the < 10 ms group was better than that of the 10 to 20 ms group; the 10 to 20 ms group was better than that of the > 20 ms group; the peak decrease of the < 30% group was better than that of the 30% to 50% group; and the 30% to 50% group was better than that of the > 50% group (P < .05). The visual acuity regression of amblyopia in the 0.5 to 1-year group was higher than that in the other 2 groups (P < .05). This study confirms that adult amblyopia can still be cured under certain conditions. This visual plasticity is related to age, initial visual acuity, and excitability of the visual center. This study provides new clinical evidence and diagnostic ideas for the study of the pathogenesis of adult amblyopia.
Case control study: G-allele of rs4244165 in JAK1 gene correlated with high-level brief psychiatric rating scale in bipolar patients
Authors: Benkortbi Elouaer Akila Ahlem Elouaer , Ben Mohamed Bochra , Zaafrane Ferid , Gaha Lotfi , Bel Hadj Jrad Tensaout Besma
Published: September 2023

Bipolar disorder (BD) is a chronic and clinically complex disease, characterized by pathological disturbances in mood and energy. Cytokines can access the brain and their signaling pathways affect brain functions, such as neurotransmitter metabolism, neuroendocrine function, neural/synaptic plasticity, and mood neural circuitry. JAK 1 is the most common phosphorylation protein combined with the tyrosine kinase cytokine receptors; therefore, we investigated the association between the Janus family kinase 1 (JAK1) gene polymorphisms (rs2780895, rs4244165, and rs17127024) and susceptibility to BD. The case study population included 93 patients diagnosed with BD and 112 healthy controls, selected from the central coastal region of Tunisia. Polymerase chain reaction-restriction fragment length polymorphism was used to investigate these 3 JAK1 polymorphisms. We compared the sociodemographic and clinical parameters of 3 genotypes of this single nucleotide polymorphisms rs2780895, rs4244165, and rs17127024 of the JAK1 gene. The frequencies of the 3 genotypes were similar in the patient and control groups. One-way analysis of variance revealed a significant variation in rs4244165. After hospitalization, the average of the brief psychiatric rating scale score was significantly higher for the wild-type GG genotype than that for the double-mutation TT genotype (31.23% vs 22.85%, P = .043). The least significant difference post hoc test also showed a significant difference between the GG and TT genotypes at both hospital admission (P = .001) and after hospitalization (P = .012), with the GG genotype being associated with a higher brief psychiatric rating scale score. Haplotypic analysis revealed that the wild-type haplotype with the highest frequency (46.62%) was CTG. Our results showed no association between the 3 studied positions and bipolar disorder. However, the G-allele of rs4244165 in JAK1 is associated with the highest level of the brief psychiatric rating scale in patients with bipolar disorder. The JAK/signal transducer and activator of transcription pathway is an interesting therapeutic route that requires further investigations. Studying their regulatory regions can provide a clearer picture of all the interactions involved in the regulation of genetic expression in response to treatment.
Expression and clinical significance of METTL3 in colorectal cancer
Authors: Li Hui , Liu Zhilin , Wang Haitao
Published: September 2023

Methyltransferase-like 3 (METTL3) belongs to the class I MTase family, and it has been proved that METTL3 is highly expressed in a variety of tumors and promotes tumor progression. Our previous studies have shown that METTL3 is highly expressed in gastric cancer tissues compared with para-cancer tissues, and its expression level is negatively correlated with good postoperative prognosis of patients. To explore the expression of METTL3 in colorectal cancer (CRC) tissue and the relationship between METTL3 and the clinicopathologic features and prognosis of CRC patients. The expression of METTL3 in cancer tissues and adjacent tissues of 180 patients with colorectal cancer was analyzed by tissue microarray and immunohistochemistry. The clinicopathologic features of patients with different METTL3 expression levels were analyzed. The expression level of METTL3 in colorectal cancer tissues was higher than that in adjacent tissues (P < .05). There were statistically significant differences in the expression of METTL3 in clinical stage, survival time and distant metastasis (all P < .05). The expression level of METTL3 in colorectal cancer tissues with tumor-node-metastasis stage III and IV and distant metastasis was higher than that in clinical stage I and II and without distant metastasis (P < .05). Patients with high METTL3 expression had a higher overall mortality rate compared to patients with low METTL3 expression, and the difference was statistically significant (P < .05). Univariate Cox regression analysis suggested that tumor distant metastasis, vascular invasion, pathological grade, lymph node metastasis and METTL3 expression level were risk factors for overall survival in CRC patients (all P < .05). Multivariate Cox regression analysis suggested that low pathological grade (hazard ratio = 1.695, 95% confidence interval: 1.116–2.274, P = .005) and high METTL3 expression (hazard ratio = 2.156, 95% confidence interval: 1.587–2.725, P < .001) could be used as independent risk factors for prognosis assessment. The expression of METTL3 was increased in colorectal cancer, and METTL3 was closely related to clinical stage, distant metastasis and prognosis of colorectal cancer.
Current state of interventional procedures to treat pernicious placenta previa accompanied by placenta accreta spectrum: A review
Authors: Zhao Hu , Wang Qiong , Han Mou , Xiao Xue
Published: September 2023

Pernicious placenta previa (PPP) accompanied by placenta accreta spectrum (PAS) is a life-threatening placental implantation that causes a variety of complications, including antepartum hemorrhage, postpartum hemorrhage, hemorrhagic shock, preterm birth, and neonatal asphyxia. Along with continuous improvements in medical technology, interventional procedures have been widely used to prevent intraoperative hemorrhage associated with PPP. The commonly used interventional procedures include abdominal aorta clamping, prophylactic balloon occlusion of the internal or common iliac arteries, and uterine artery embolization. The above-mentioned interventional procedures have their respective advantages and disadvantages. The best procedure for different situations continues to be debated considering the complex pattern of blood supply to the uterus in patients with PPP. The specific choice of interventional procedure depends on the clinical situation of the patient with PPP. For grade III PAS, the need for uterine artery embolization is assessed based on blood loss and preoperative hemostatic effect following abdominal aorta clamping. Repair or hysterectomy may be performed following uterine artery embolization if there is a hybrid operating room for grade III PAS patients with extensive sub-serosal penetration of the uterus and repair difficulty. For grade II PAS (shallow placental implantation), prophylactic balloon occlusion may not be necessary before surgery. Uterine artery embolization can be performed in case of postoperative hemorrhage.