bluuebunny/crossref_metadata_2025 huggingface dataset:
Apoptosis-related factors are relevant to progression of pancreatic neuroendocrine tumors
Authors: Amano Shota , Hirashita Teijiro , Kawano Yoko , Nishida Haruto , Orimoto Hiroki , Kawamura Masahiro , Kawasaki Takahide , Masuda Takashi , Endo Yuichi , Ohta Masayuki , Daa Tsutomu , Inomata Masafumi
Published: December 2023

Background

Multidisciplinary therapy centered on antitumor drugs is indicated in patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, the criteria for selection of optimal therapeutic agents is controversial. The aim of this study was to assess the malignancy of PanNET for optimal therapeutic drug selection.

Methods

Forty-seven patients with PanNET who underwent surgery were reviewed retrospectively, and immunohistochemical characteristics, including expression of GLUT1, SSTR2a, SSTR5, Survivin, X-chromosome-linked inhibitor of apoptosis protein (XIAP), and Caspase3 in the resected specimens, were investigated. Relapse-free survival (RFS) and overall survival (OS) were evaluated with regard to the characteristics using the Kaplan–Meier method and compared with the log-rank test.

Results

GLUT1 expression showed significant correlation with sex (p = 0.036) and mitotic rate (p = 0.048). Survivin and XIAP expression showed significant correlation with T-stage (p = 0.014 and 0.009), p-Stage (p = 0.028 and 0.045), and mitotic rate (p = 0.023 and 0.007). XIAP expression also significantly influenced OS (p = 0.044).

Conclusions

Survivin and XIAP correlated with grade of malignancy, and expression of XIAP in particular was associated with a poor prognosis. Expression of these proteins may be a useful indicator to select optimal therapeutic agents in PanNET.
SPOCK1, as a potential prognostic and therapeutic biomarker for lung adenocarcinoma, is associated with epithelial-mesenchymal transition and immune evasion
Authors: Liu Yafeng , Han Tao , Wu Jing , Zhou Jiawei , Guo Jianqiang , Miao Rui , Xu Zhi , Xing Yingru , Bai Ying , Hu Dong
Published: December 2023

Background

The occurrence of epithelial-mesenchymal transition (EMT) and immune evasion is considered to contribute to poor prognosis in lung adenocarcinoma (LUAD). Therefore, this study aims to explore the key oncogenes that promote EMT and immune evasion and reveal the expression patterns, prognostic value, and potential biological functions.

Methods

Firstly, we identified gene modules associated with EMT and Tumor Immune Dysfunction and Exclusion (TIDE) through weighted gene co-expression network analysis (WGCNA). Next, we utilized differential analysis and machine learning to identify the key genes and validate them. Moreover, we analyzed the correlation between key genes and tumor microenvironment remodeling, drug sensitivity, as well as mutation frequency. Furthermore, we explored and validated their malignant biological characteristics through in vitro experiments and clinical samples. Finally, potential drugs for LUAD were screened based on CMap and validated through experiments.

Results

Firstly, WGCNA analysis revealed that red and green modules were highly correlated with EMT and TIDE. Among them, upregulated expression of SPOCK1 was observed in lung adenocarcinoma tissues and was associated with poor prognosis. Additionally, patients in the high SPOCK1 group showed more activation of malignant oncogenic pathways, higher infiltration of immunosuppressive components, and a higher frequency of mutations. The knockdown of SPOCK1 suppressed invasion and metastasis capabilities of lung adenocarcinoma cells, and the high expression of SPOCK1 was associated with low infiltration of CD8+ T cells. Therapeutic aspects, SPOCK1 can be a candidate indicator for drug sensitivity and CMap showed that VER-155008 was the drug candidate with the largest perturbation effect on the SPOCK1 expression profile. In vitro and in vivo experiments validated the cancer-inhibitory effect of VER-155008 in LUAD.

Conclusion

This study revealed through comprehensive bioinformatics analysis and experimental analysis that SPOCK1 can promote EMT and immune escape in LUAD, and it may serve as a promising candidate prognostic biomarker and therapeutic target for LUAD.
Rudolph, the kids’ ward reindeer: a scoping review of the effects of support animals on the well-being of healthcare staff
Authors: Erren Thomas C. , Wallraff Jonas , Wild Ursula , Shaw David M. , Lewis Philip
Published: December 2023

Background

Many systematic reviews identify support animals or animal assisted activity as a beneficial and standard practice in several medical disciplines for patients (children, adolescents, and adults) and residents in care homes. A variety of animals are used such as dogs, cats, ponies, horses, alpacas, reindeer, penguins, rabbits, and tarantulas. Our objective was to explore the evidence regarding effects of animal assisted activity on a further population of interest; namely, healthcare staff.

Methods

We asked the question “how do support animals in healthcare settings affect the well-being of healthcare staff?” As an addendum, we were also interested in what - possibly more unique - animals have visited healthcare settings at Christmas time in particular. We conducted a scoping literature review using PubMed and Web of Science (search as of 26 April 2023). 

Results

Twenty studies (in the USA, Australia, Europe; dogs: n = 19; cats: n = 1) since 2002 included: studies with biological measures (n = 3), longitudinal survey studies with analyses (n = 5), cross-sectional survey studies with analyses (n = 2), and cross-sectional survey studies with descriptive statistics (n = 10). Overall, animal assisted activities appear to be well-received by staff and there do not seem to be negative impacts on staff well-being.

Conclusions

Relevant positive effects and avenues of research are identified. Our review suggests that, but not exactly how, animal assisted activity benefits staff. Study evidence is limited with most studies being cross-sectional, descriptive, having low participant numbers, and mostly only involving dogs. Nonetheless, the evidence is mostly positive. The potential of animal assisted activities impacting positively on staff well-being warrants systematic research. Gaps in hard-fact-evidence should not deter us – especially at the festive season – to encourage work with, and systematic research regarding, support animals that provide warmth, empathy, comfort, and more in healthcare settings.
Considerations for the design of antibody drug conjugates (ADCs) for clinical development: lessons learned
Authors: López de Sá Alfonso , Díaz-Tejeiro Cristina , Poyatos-Racionero Elisa , Nieto-Jiménez Cristina , Paniagua-Herranz Lucía , Sanvicente Adrián , Calvo Emiliano , Pérez-Segura Pedro , Moreno Víctor , Moris Francisco , Ocana Alberto
Published: December 2023

Antibody–drug conjugates (ADCs) have emerged as a novel therapeutic strategy that has successfully reached patient treatment in different clinical scenarios. ADCs are formed by an antibody against a specific tumor-associated antigen (TAA), a cytotoxic payload, and a chemical linker that binds both. To this regard, most efforts have been focused on target identification, antibody design and linker optimization, but other relevant aspects for clinical development have not received the necessary attention. In this article using data from approved ADCs, we evaluated all characteristics of these agents, including payload physicochemical properties, in vitro potency, drug antibody ratio (DAR), exposure–response relationships, and clinical development strategies. We suggest that compounds with best options for clinical development include those with optimal payload physicochemical properties and cleavable linkers that would lead to a bystander effect. These modalities can facilitate the development of ADCs in indications with low expression of the TAA. Early clinical development strategies including changes in the schedule of administration with more frequent doses are also discussed in the context of an efficient strategy. In conclusion, we highlight relevant aspects that are needed for the optimal development of ADCs in cancer, proposing options for improvement.
Ankle osteoarthritis: an online survey of current treatment practices of UK‐based podiatrists and physiotherapists
Authors: Callaghan Michael J. , Gala Jinal Pravin , Roddy Edward
Published: December 2023

Background

Patients with painful ankle osteoarthritis (OA) have a mixed experience of non‐surgical management which they may attribute to a lack of guidance for clinicians on usual care treatment. Therefore, the purpose of this study was to survey the current clinical practices of UK‐based physiotherapists and podiatrists for the treatment of painful ankle osteoarthritis (OA).

Methods

UK‐based physiotherapists and podiatrists who treat patients with ankle OA completed a self‐administered online questionnaire about their professional and clinical service characteristics, diagnostic criteria, treatment aims, preferred treatment options, and treatment outcome measures. Data were collected anonymously and stored on JISC online survey. ‘Usual care’ was defined as a combination of ‘Always’, and ‘Frequently’, and ‘Not usual care’ was defined as ‘Sometimes’ ‘Rarely,’ ‘Never’, and ‘not applicable’ combined. Statistically significant differences in responses between the physiotherapists and podiatrists were analysed using X2 tests for each treatment modality. Statistical significance was set at p < 0.05.

Results

Between 1st June 2021 and 31st August 2021, 100 responses were received; 2 were invalid. Of the 98 valid responses, 63 were from physiotherapists and 35 from podiatrists. The most common treatment aims in both professions were to reduce pain (n = 87, 89%) and improve quality of life (n = 82, 84%). 50 respondents (51%) offered 3 or 4 treatment sessions and 53 respondents (54%) saw patients for 30–40 min at the first treatment session.

The five most common modalities used by physiotherapists were patient education (n = 63, 100%), teaching self‐management (n = 58, 92%), lifestyle modification (n = 54, 86%), ankle strengthening (n = 55, 87%), and proprioception exercises (n = 54, 86%). For podiatrists, these were patient education (n = 35, 100%), ankle strengthening (n = 31, 89%), activity pacing (n = 28, 80%), lifestyle modification (n = 27, 77%), and gait training (n = 27, 77%).

Conclusions

This first‐ever survey revealed physiotherapists’ and podiatrists’ current practices to treat painful ankle OA. This study provides a better understanding of how ankle OA is treated in UK current clinical practice and can inform future clinical trials to compare current practice with new treatment modalities.
Evaluating the use of paralogous protein domains to increase data availability for missense variant classification
Authors: Gunning Adam Colin , Wright Caroline Fiona
Published: December 2023

Background

Classification of rare missense variants remains an ongoing challenge in genomic medicine. Evidence of pathogenicity is often sparse, and decisions about how to weigh different evidence classes may be subjective. We used a Bayesian variant classification framework to investigate the performance of variant co-localisation, missense constraint, and aggregating data across paralogous protein domains (“meta-domains”).

Methods

We constructed a database of all possible coding single nucleotide variants in the human genome and used PFam predictions to annotate structurally-equivalent positions across protein domains. We counted the number of pathogenic and benign missense variants at these equivalent positions in the ClinVar database, calculated a regional constraint score for each meta-domain, and assessed this approach versus existing missense constraint metrics for classifying variant pathogenicity and benignity.

Results

Alternative pathogenic missense variants at the same amino acid position in the same protein provide strong evidence of pathogenicity (positive likelihood ratio, LR+  = 85). Additionally, clinically annotated pathogenic or benign missense variants at equivalent positions in different proteins can provide moderate evidence of pathogenicity (LR+  = 7) or benignity (LR+  = 5), respectively. Applying these approaches sequentially (through PM5) increases sensitivity for classifying pathogenic missense variants from 27 to 41%. Missense constraint can also provide strong evidence of pathogenicity for some variants, but its absence provides no evidence of benignity.

Conclusions

We propose using structurally equivalent positions across related protein domains from different genes to augment evidence for variant co-localisation when classifying novel missense variants. Additionally, we advocate adopting a numerical evidence-based approach to integrating diverse data in variant interpretation.
Proof-of-concept recall-by-genotype study of extremely low and high Alzheimer’s polygenic risk reveals autobiographical deficits and cingulate cortex correlates
Authors: Lancaster Thomas , Creese Byron , Escott-Price Valentina , Driver Ian , Menzies Georgina , Khan Zunera , Corbett Anne , Ballard Clive , Williams Julie , Murphy Kevin , Chandler Hannah
Published: December 2023

Background

Genome-wide association studies demonstrate that Alzheimer’s disease (AD) has a highly polygenic architecture, where thousands of independent genetic variants explain risk with high classification accuracy. This AD polygenic risk score (AD-PRS) has been previously linked to preclinical cognitive and neuroimaging features observed in asymptomatic individuals. However, shared variance between AD-PRS and neurocognitive features are small, suggesting limited preclinical utility.

Methods

Here, we recruited sixteen clinically asymptomatic individuals (mean age 67; range 58–76) with either extremely low / high AD-PRS (defined as at least 2 standard deviations from the wider sample mean (N = 4504; NEFFECTIVE = 90)) with comparable age sex and education level. We assessed group differences in autobiographical memory and T1-weighted structural neuroimaging features.

Results

We observed marked reductions in autobiographical recollection (Cohen’s d =  − 1.66; PFDR = 0.014) and midline structure (cingulate) thickness (Cohen’s d =  − 1.55, PFDR = 0.05), with no difference in hippocampal volume (P > 0.3). We further confirm the negative association between AD-PRS and cingulate thickness in a larger study with a comparable age (N = 31,966, β =  − 0.002, P = 0.011), supporting the validity of our approach.

Conclusions

These observations conform with multiple streams of prior evidence suggesting alterations in cingulate structures may occur in individuals with higher AD genetic risk. We were able to use a genetically informed research design strategy that significantly improved the efficiency and power of the study. Thus, we further demonstrate that the recall-by-genotype of AD-PRS from wider samples is a promising approach for the detection, assessment, and intervention in specific individuals with increased AD genetic risk.
Predicting positron emission tomography brain amyloid positivity using interpretable machine learning models with wearable sensor data and lifestyle factors
Authors: Kimura Noriyuki , Aota Tomoki , Aso Yasuhiro , Yabuuchi Kenichi , Sasaki Kotaro , Masuda Teruaki , Eguchi Atsuko , Maeda Yoshitaka , Aoshima Ken , Matsubara Etsuro
Published: December 2023

Background

Developing a screening method for identifying individuals at higher risk of elevated brain amyloid burden is important to reduce costs and burden to patients in clinical trials on Alzheimer’s disease or the clinical setting. We developed machine learning models using objectively measured lifestyle factors to predict elevated brain amyloid burden on positron emission tomography.

Methods

Our prospective cohort study of non-demented, community-dwelling older adults aged ≥ 65 years was conducted from August 2015 to September 2019 in Usuki, Oita Prefecture, Japan. One hundred and twenty-two individuals with mild cognitive impairment or subjective memory complaints (54 men and 68 women, median age: 75.50 years) wore wearable sensors and completed self-reported questionnaires, cognitive test, and positron emission tomography imaging at baseline. Moreover, 99 individuals in the second year and 61 individuals in the third year were followed up. In total, 282 eligible records with valid wearable sensors, cognitive test results, and amyloid imaging and data on demographic characteristics, living environments, and health behaviors were used in the machine learning models. Amyloid positivity was defined as a standardized uptake value ratio of ≥ 1.4. Models were constructed using kernel support vector machine, Elastic Net, and logistic regression for predicting amyloid positivity. The mean score among 10 times fivefold cross-validation repeats was utilized for evaluation.

Results

In Elastic Net, the mean area under the receiver operating characteristic curve of the model using objectively measured lifestyle factors alone was 0.70, whereas that of the models using wearable sensors in combination with demographic characteristics and health and life environment questionnaires was 0.79. Moreover, 22 variables were common to all machine learning models.

Conclusion

Our machine learning models are useful for predicting elevated brain amyloid burden using readily-available and noninvasive variables without the need to visit a hospital.

Trial registration

This prospective study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of Oita University Hospital (UMIN000017442). A written informed consent was obtained from all participants. This research was performed based on the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.
Towards a socially vibrant city: exploring urban typologies and morphologies of the emerging “CityWalks” in Dubai
Authors: Kordi Alaa Omar , Galal Ahmed Khaled
Published: December 2023

Vertical urbanization to maximize land use in many cities has led to a shortage of urban spaces that could adequately meet people's needs. In response, CityWalk has emerged as a new urban form to solve this problem by attracting people to go from inside closed buildings to outside walks. Thus, it is promoting health, economy, and tourism. Locally in the United Arab Emirates (UAE), especially in Dubai, a limited number of CityWalks have been developed. Despite the increasing popularity of CityWalks, there has been a gap in research examining their distinct emerging urban typologies and their urban configuration. This study seeks to address this gap by first conceptualizing CityWalk as an emerging urban public space based on the exploration of global and local experiences. Second, the study categorized the morphological configuration of three selected case studies of CityWalks in Dubai using Geographic Information System (GIS) tools. These case studies represent three different developments of CityWalks in three different contexts in the UAE. First, CityWalks within the inner city's urban context are represented by ‘City Walk’ in Al Wasel. Second, CityWalks surrounded by the sea represented by 'The Walk’ in Marsa Dubai. Third, CityWalks developed next to traditional buildings represented by ‘Al Seef’ in Al Hamriya. The findings of the research investigations reveal that the emerging ‘CityWalks’ developments in each of the three different urban contexts in Dubai do not represent a single familiar urban space typology but rather a ‘harmonious’ blend of global and local urban design typologies. In addition, the urban morphological analysis of these three urban developments underscores the distinctive characteristics of each of them in terms of street network, urban form, urban compactness, land use, and shading. This contributes to better understanding of these emerging urban forms and hence pave the way for more research about their socio-economic robustness to ultimately contribute to more successful future designs of ‘CityWalks’ in Dubai and other cities in the region.
The Effects of Doxorubicin Loaded Aptamer S3-Linked DNA Tetrahedrons on Nasopharyngeal Carcinoma
Authors: Liu Xiwu , Jiang Bincan , Cheng Ailan , Guo Youwei , Wang Lei , Liu Weidong , Yin Wen , Li Yihan , Jiang Xingjun , Ren Caiping
Published: December 2023

Objective

Our research group in the early stage identified CD109 as the target of aptamer S3 in nasopharyngeal carcinoma (NPC). This study was to use S3 to connect DNA tetrahedron (DT) and load doxorubicin (Dox) onto DT to develop a targeted delivery system, and explore whether S3-DT-Dox can achieve targeted therapy for NPC.

Methods

Aptamer S3-conjugated DT was synthesized and loaded with Dox. The effects of S3-DT-Dox on NPC cells were investigated with laser confocal microscopy, flow cytometry, and MTS assays. A nude mouse tumor model was established from NPC 5-8F cells, and the in vivo anti-tumor activity of S3-DT-Dox was examined by using fluorescent probe labeling and hematoxylin–eosin staining.

Results

The synthesized S3-DT had high purity and stability. S3-DT specifically recognized 5-8F cells and NPC tissues in vitro. When the ratio of S3-DT to Dox was 1:20, S3-DT had the best Dox loading efficiency. The drug release rate reached the maximum (0.402 ± 0.029) at 48 h after S3-DT-Dox was prepared and mixed with PBS. S3-DT did not affect Dox toxicity to 5-8F cells, but reduced Dox toxicity to non-target cells. Meanwhile, S3-DT-Dox was able to specifically target the transplanted tumors and inhibit their growth in nude mice, with minor damage to normal tissues.

Conclusion

Our study highlights the ability and safety of S3-DT-Dox to target NPC cells and inhibit the development NPC.

Graphical abstract
Nuclear face of Tau: an inside player in neurodegeneration
Authors: Younas Neelam , Saleem Tayyaba , Younas Abrar , Zerr Inga
Published: December 2023

Tau (Tubulin associated unit) protein is a major hallmark of Alzheimer’s disease (AD) and tauopathies. Tau is predominantly an axonal protein with a crucial role in the stabilization and dynamics of the microtubules. Since the discovery of Tau protein in 1975, research efforts were concentrated on the pathophysiological role of Tau protein in the context of the microtubules. Although, for more than three decades, different localizations of Tau protein have been discovered e.g., in the nuclear compartments. Discovery of the role of Tau protein in various cellular compartments especially in the nucleus opens up a new fold of complexity in tauopathies. Data from cellular models, animal models, and the human brain indicate that nuclear Tau is crucial for genome stability and to cope with cellular distress. Moreover, it’s nature of nuclear translocation, its interactions with the nuclear DNA/RNA and proteins suggest it could play multiple roles in the nucleus. To comprehend Tau pathophysiology and efficient Tau-based therapies, there is an urgent need to understand whole repertoire of Tau species (nuclear and cytoplasmic) and their functional relevance. To complete the map of Tau repertoire, understanding of various species of Tau in the nucleus and cytoplasm, identification if specific transcripts of Tau, isoforms and post-translational modifications could foretell Tau’s localizations and functions, and how they are modified in neurodegenerative diseases like AD, is urgently required. In this review, we explore the nuclear face of Tau protein, its nuclear localizations and functions and its linkage with Alzheimer’s disease.
Store of value or speculative investment? Market reaction to corporate announcements of cryptocurrency acquisition
Authors: Gimenes André D. , Colombo Jéfferson A. , Yousaf Imran
Published: December 2023

In this study, we analyze the stock market reaction to 35 events associated with 32 publicly traded companies from six countries that have announced cryptocurrency acquisitions, selling, or acceptance as a means of payment. Our analysis focuses on traditional firms whose core business is unrelated to blockchain or cryptocurrency. We find that the aggregate market reaction around these events is slightly positive but statistically insignificant for most event windows. However, when we perform heterogeneity analyses, we observe significant differences in market reaction between events with high (larger CARs) and low cryptocurrency exposure (lower CARs). Multivariate regressions show that the level of exposure to cryptocurrency ("skin in the game") is a critical factor underlying abnormal returns around the event. Further analyses reveal that economically meaningful acquisitions of BTC or ETH (relative to firm's total assets) drive the observed effect. Our findings have important implications for managers, investors, and analysts as they shed light on the relationship between cryptocurrency adoption and firm value.
Evaluation of adjuvants for reducing the risk of phytotoxicity in low-volume spray of propiconazole
Authors: Teng Lijie , Gao Tuqiang , Gu Anyu , Zhang Qizhen , Hu Maolin , Hao Jianjun , Li Xiaolin , Liu Pengfei
Published: December 2023

Unmanned aerial vehicles (UAVs) have been increasingly employed for fungicide applications in plant disease control. However, due to weight limitations, the fungicides sprayed through UAVs must be in low volumes with high concentrations in many instances, which may result in potential phytotoxicity. Here we evaluate the safety of low-volume spray of chemicals on rice plants. The plants were sprayed with propiconazole emulsifiable concentrate (EC) at 250 g/L mixed with various adjuvants and applied at a low volume, which contained the fungicide at concentrations equivalent to or higher than that used in UAV application. The spray adjuvants included YS-20, Biaopu adjuvant, TriTek, Yipinsongzhi, AgriSolv-C100, and Hongyuyan. Potential phytotoxicity on rice plants was examined based on surface tension and crop growth. Additives suitable for a low-volume spray of propiconazole were also assessed on three rice varieties for phytotoxicity. The results showed that after 72 h of fungicide application at 2, 4, and 8 times the recommended dose of 7500 μg/mL for UAV spray, rice leaves exhibited abnormal growth, and the dry weight of rice significantly decreased 21 days after application. Phytotoxicity was evaluated on three rice varieties 5 days after spraying propiconazole EC at 2 × recommended dose with one of the spray adjuvants. The addition of 1% YS-20, Biaopu adjuvant, TriTek, and Yipinsongzhi significantly augmented the phytotoxicity. However, both AgriSolv-C100 and Hongyuyan significantly reduced the comprehensive index of phytotoxicity and, therefore, could be used for UAV applications.
Coping strategies and burden stress in caregivers of patients with schizophrenia and patients with bipolar disorder
Authors: Mohamed Rehab Serag , Mahmoud Nivert Zaki , Mahmoud Dalia Abdel Moneim , Eissa Mohamed Fekry , Zohdy Youssef Wael , Hafez Yassmin Shawky Rateb
Published: December 2023

Background

Mental illness has a great impact not only on patients but also on their carers as it makes them more prone to stress, interferes with their daily life activities, and can negatively affect their social, psychological, and physical health quality of life. They neglect seeking medical help that may negatively affect clinical outcome of patients and quality of their life. Therefore, it is important to evaluate the magnitude of burden on such caregivers and to investigate the coping strategies used by them in order to develop tailored biopsychosocial interventions to reduce their stress.

Objective

To assess the magnitude of burden and patterns of coping with stress in caregivers of patients with schizophrenia. To assess the magnitude of burden and patterns of coping with stress in caregivers of patients with bipolar affective disorder. To compare both the coping strategies and burden stress scores among carers of patients diagnosed with schizophrenia and bipolar patients.

Patients and methods

This cross-sectional study was done on 100 caregivers to assess burden in caregivers of schizophrenia patients and caregivers of bipolar patients, the coping style used by the caregivers of both groups and comparing between two groups.

Results

There was statistically significant difference found between bipolar group and schizophrenia group regarding coping inventory scores make fun and behavioral withdrawal, which showed higher median score in schizophrenia group than bipolar group. Burden of caring and coping with this burden, affect each other mutually. As, according to the results of our study, rural residence of caregiver, positive reassessment ≤ 12 and denial > 8 were found significantly associated with high burden in bipolar group. While employed caregivers were associated with high burden among schizophrenia group. Burden is higher in bipolar group than schizophrenia group.

Conclusion

The burden placed on caregivers has a significant impact on their capacity to offer service and care to patients. It also has an impact on how service providers adjust to and deal with their families' illnesses. Reduced caregiver load and increased awareness of the condition may help caregivers to use more flexible coping techniques.
Designing Activities to Teach Higher-Order Skills: How Feedback and Constraint Affect Learning of Experimental Design
Authors: Meir Eli , Pope Denise , Abraham Joel K. , Kim Kerry J , Maruca Susan , Palacio Jennifer
Published: December 2023

Active learning approaches enhance student learning, but what features promote optimal learning? By manipulating the design of a simulation-based tutorial on experimental design, we find specific immediate feedback has direct positive learning effects, while small changes in constraint has little effect, suggesting guidance for activity design.
Long-term Risk for Type 1 Diabetes and Obesity in Early Term Born Offspring: A Systematic Review and Meta-Analysis
Authors: Tsaitlin-Mor Lilah , Cahen-Peretz Adva , Bentov Yaakov , Ben-Shushan Tomer , Levine Hagai , Walfisch Asnat
Published: December 2023

Context

Prematurity increases the long-term risks for endocrine and metabolic morbidity of offspring, but there is uncertainty regarding the risks for early-term deliveries (370/7-386/7 weeks of gestation).

Objective

We aim to evaluate whether early-term deliveries increase the long-term risk for type 1 diabetes and obesity of offspring up to the age of 18 years compared with full-term children. PubMed, Medline, and EMBASE were searched. Observational cohort studies addressing the association between early-term delivery and long-term risk for type 1 diabetes and obesity, were included. Two independent reviewers extracted data and assessed risk of bias. Pooled relative risks (RRs) and heterogeneity were determined. Publication bias was assessed by funnel plots with Egger's regression line and contours, and sensitivity analyses were performed.

Results

Eleven studies were included following a screen of 7500 abstracts. All studies were scored as high quality according to the Newcastle–Ottawa Quality Assessment Scale. Early-term delivery was significantly associated with an increased risk for type 1 diabetes (RR 1.19, 1.13-1.25), while the association was weaker for overweight and obesity (RR 1.05, 0.97-1.12). It is challenging to determine whether the association between early-term births and long-term morbidity represents a cause and effect relationship or is attributable to confounders. Most of the included studies adjusted for at least some possible confounders.

Conclusion

Compared with full-term offspring, early-term delivery poses a modest risk for long-term pediatric type 1 diabetes. Our analysis supports that, whenever medically possible, elective delivery should be avoided before 39 completed weeks of gestation.
Adult-type Diffuse Gliomas
Authors: de la Fuente Macarena I.
Published: December 2023

OBJECTIVE

This article highlights key aspects of the diagnosis and management of adult-type diffuse gliomas, including glioblastomas and IDH-mutant gliomas relevant to the daily practice of the general neurologist.

LATEST DEVELOPMENTS

The advances in molecular characterization of gliomas have translated into more accurate prognostication and tumor classification. Gliomas previously categorized by histological appearance solely as astrocytomas or oligodendrogliomas are now also defined by molecular features. Furthermore, ongoing clinical trials have incorporated these advances to tailor more effective treatments for specific glioma subtypes.

ESSENTIAL POINTS

Despite recent insights into the molecular aspects of gliomas, these tumors remain incurable. Care for patients with these complex tumors requires a multidisciplinary team in which the general neurologist has an important role. Efforts focus on translating the latest data into more effective therapies that can prolong survival.
2021 World Health Organization Classification of Brain Tumors
Authors: Meredith David M. , Pisapia David J.
Published: December 2023

Objective

The classification of brain tumors is a rapidly evolving field that requires extensive integration of molecular diagnostic findings from an expanding set of platforms and assays. This article summarizes the schema presented in the 5th edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors while highlighting diagnostic molecular findings and discussing the strengths and weaknesses of commonly available testing modalities.

Latest Developments

Several major changes in practice were introduced with the 5th edition of the CNS WHO classification, including molecular grading of adult diffuse gliomas, the introduction of many new entities within the spectrum of pediatric gliomas and glioneuronal tumors, and the widespread adoption of methylation classes as useful or even necessary diagnostic criteria. Additionally, several revisions to nomenclature (eg, IDH-mutant gliomas) were introduced for simplicity and to disambiguate from other tumor types.

Essential Points

The classification of brain tumors continues to grow in complexity alongside our improved understanding of their nuanced molecular underpinnings.
Central Nervous System Lymphoma
Authors: Schaff Lauren
Published: December 2023

OBJECTIVE

This article reviews the clinical presentation, diagnostic workup, staging, and treatment of primary central nervous system (CNS) lymphoma and common manifestations of secondary CNS lymphoma.

LATEST DEVELOPMENTS

Lymphoma can arise in the CNS de novo (primary CNS lymphoma) or as the result of systemic disease (secondary CNS lymphoma). Symptoms may include focal neurologic deficits related to the disease site, cognitive decline, and symptoms of increased intracranial pressure. Standard treatment may differ based on lymphoma subtype and location. A majority of CNS lymphoma is diffuse large B-cell subtype and exhibits aggressive behavior. First-line treatment is generally methotrexate-based polychemotherapy. Response rates to treatment are high, approximately 80% to 90% for primary CNS lymphoma, but relapse is common. Consolidation approaches including myeloablative chemotherapy followed by autologous stem cell rescue, nonmyeloablative chemotherapy, radiation, and medical maintenance regimens reduce rates of relapse. The recent development of targeted agents such as Bruton tyrosine kinase inhibitors and immunomodulatory strategies have shown promise in the treatment of CNS lymphoma. Immunotherapy in the form of checkpoint inhibitors and chimeric antigen receptor T cells is being studied. More indolent forms of lymphoma may be treated with radiation or targeted therapy.

ESSENTIAL POINTS

CNS lymphoma is an uncommon but clinically meaningful manifestation of extranodal lymphoma. The diagnosis requires a high level of suspicion for rapid initiation of potentially curative treatment.
Paraneoplastic Neurologic Syndromes
Authors: Graber Jerome J.
Published: December 2023

OBJECTIVE

Progress is ongoing in understanding paraneoplastic neurologic disorders, with new syndromes and antibodies being described and more detailed evidence available to guide workup for diagnosis and treatment to improve outcomes. Many excellent reviews have summarized the molecular features of different antibodies, but this article emphasizes the clinical features of each syndrome that may help guide initial diagnosis and treatment, which often should occur before an antibody or cancer is found to confirm the diagnosis.

LATEST DEVELOPMENTS

Recent findings include updated diagnostic criteria with validated sensitivity and specificity, discovery of novel antibodies, and clinical findings that increase the likelihood of an underlying paraneoplastic disorder. Suggestive syndromes that have been recently identified include faciobrachial dystonic seizures and pilomotor auras in anti–leucine-rich glioma inactivated protein 1 encephalitis, extreme delta brush on EEG inN-methyl-d-aspartate (NMDA)-receptor encephalitis, déjà vu aura in anti–glutamic acid decarboxylase 65 (GAD65) encephalitis, and sleep disturbances in several disorders. In addition, there is confirmed utility of brain positron emission tomography (PET) and CSF markers, including carcinoembryonic antigen and oligoclonal bands, as well as improved tests for the presence of leptomeningeal cancer cells in CSF. Associations of cancer immunotherapies with paraneoplastic syndromes and herpes simplex virus encephalitis (and COVID-19) with NMDA-receptor encephalitis have been described.

ESSENTIAL POINTS

All neurologists should be aware of advances regarding paraneoplastic neurologic syndromes, as patients can present with a wide variety of neurologic symptoms and earlier diagnosis and treatment can improve outcomes.
Management of Complications in Neuro-oncology Patients
Authors: Welch Mary R.
Published: December 2023

OBJECTIVE

The purpose of this article is to familiarize the reader with the spectrum of neurologic and medical complications relevant to the care of patients with neurologic cancer while highlighting best practices to prevent morbidity and mortality. Topics include tumor-related epilepsy, vasogenic edema, complications of corticosteroid use, disruption of the hypothalamic-pituitary axis, venous thromboembolism, and opportunistic infection.

LATEST DEVELOPMENTS

In 2021, a joint guideline from the Society for Neuro-Oncology and the European Association of Neuro-Oncology reaffirmed recommendations first established in 2000 that patients with newly diagnosed brain tumors should not be prescribed an antiseizure medication prophylactically. For those with tumor-related epilepsy, monotherapy with a non–enzyme-inducing anticonvulsant is the preferred initial treatment, and levetiracetam remains the preferred first choice. Surveys of physician practice continue to demonstrate excessive use of glucocorticoids in the management of patients with both primary and metastatic central nervous system malignancy. This is particularly concerning among patients who require checkpoint inhibitors as the efficacy of these agents is blunted by concomitant glucocorticoid use, resulting in a reduction in overall survival. Finally, direct oral anticoagulants have been shown to be safe in patients with brain tumors and are now favored as first-line treatment among those who require treatment for venous thromboembolism.

ESSENTIAL POINTS

Medical care for patients impacted by primary and secondary central nervous system malignancy is complex and requires a committed team-based approach that routinely calls upon the expertise of physicians across multiple fields. Neurologists have an important role to play and should be familiar with the spectrum of complications impacting these patients as well as the latest recommendations for management.
Neurologic Complications of Cancer Immunotherapy
Authors: Wang Nancy
Published: December 2023

Objective

Immunotherapeutic approaches have revolutionized cancer treatment with immune checkpoint inhibitors and adoptive T-cell therapy now approved to treat a variety of solid and hematologic malignancies. This article summarizes the distinctive neurologic side effects of these therapies as well as their management.

Latest Developments

Neurologic immune-related adverse events are rare but potentially serious complications of immune checkpoint inhibitors. Both peripheral and central nervous system disorders have been described, often necessitating a pause or cessation of immunotherapy. Immune effector cell–associated neurotoxicity syndrome is a potentially serious complication of chimeric antigen receptor T-cell therapy. While symptoms may be mild and self-limited, delirium, encephalopathy, seizures, focal neurologic deficits, and fulminant cerebral edema can be seen. Close neurologic monitoring is imperative. The mainstay of treatment for neurologic complications includes high-dose corticosteroids, although other immunomodulatory strategies may be used in severe or refractory cases.

Essential Points

The spectrum of neurologic complications of cancer immunotherapy is broad, encompassing both central and peripheral nervous system disorders, indolent as well as fulminant clinical presentations, and wide-ranging severity with variable response to treatment. Early identification and multidisciplinary management are crucial to balance neurologic recovery and antitumor control.
SARS Stories
Authors: Kong Belinda
Published: December 2023

In SARS Stories, Belinda Kong delves into the cultural archive of the 2003 SARS pandemic, examining Chinese-language creative works and social practices at the epicenters of the outbreak in China and Hong Kong. As the COVID-19 pandemic has highlighted issues of anti-Asian racism and sinophobia, Kong traces how Chinese people navigated the SARS pandemic and created meaning amid crisis through cultures of epidemic expression. From sentimental romances and Cantopop songs to raunchy sex comedies and crowdsourced ghost tales, unexpected and minor genres and creators of Chinese popular culture highlight the resilience and humanity of those living through the pandemic. Rather than narrating pandemic life in terms of crisis and catastrophe, Kong argues that these works highlight Chinese practices of community, care, and love amid disease. She also highlights the persistence of orientalism in anglophone accounts of SARS index patients and global reporting on COVID-era China. Kong shows how the Chinese experiences of living with SARS can reshape global feelings toward pandemic social life and foster greater fellowship in the face of pandemics.
Cognitive Behavioral Therapy Reduces Crime and Violence over Ten Years: Experimental Evidence
Authors: Blattman Christopher , Chaskel Sebastian , Jamison Julian C. , Sheridan Margaret
Published: December 2023

Several small, short-term, or nonexperimental studies show that cognitive behavioral–informed interventions reduce antisocial behaviors over one to two years, but persistence research is rare. We followed 999 high-risk men in Liberia ten years after randomization into eight weeks of low-cost, nonspecialist-led therapy; $200 cash; both; or neither. A decade later, antisocial behaviors (such as robbery and drug selling) fell 0.2 standard deviations from therapy alone—significantly greater than the one-year impacts. Meanwhile, men who received therapy plus cash were 0.25 standard deviations less antisocial—similar to one-year results. In both cases, impacts were concentrated in men exhibiting highest baseline risk. (JEL D91, K42, O15, O17)
India Is Broken: A People Betrayed, Independence to Today
Authors: Swamy Anand V.
Published: December 2023

Anand V. Swamy of Williams College reviews “India Is Broken: A People Betrayed, Independence to Today” by Ashoka Mody. The Econlit abstract of this book begins: “Presents a narrative of the modern history of India from the perspectives of successive Indian leaders, chronicling the erosion of social norms and decay of political accountability from 1947 to 2021 that have detrimentally affected the country's economy and political system.”
Παίζουμε βιβλίο; Πώς να αγαπήσουν τα παιδιά το διάβασμα
Authors: Ξανθοπούλου Βίκυ
Published: December 2023

Παίζουμε βιβλίο; Πώς να αγαπήσουν τα παιδιά το
διάβασμα
Παιδί σε κίνδυνο. Βασικά θεσμικά ζητήματα για τον εκπαιδευτικό
Authors: Ρουμελιώτου Αγγελική
Published: December 2023

Παιδί σε κίνδυνο.Βασικά θεσμικά ζητήματα για τον
εκπαιδευτικό
A Handful of Traditional Songs
Authors: Παπάς Νείλος
Published: December 2023

Το άρθρο περιγράφει την εκτέλεση και πραγματοποίηση ενός ευρωπαϊκού project μέσω του καινοτόμου προγράμματος eTwinning και σε συνεργασία με ευρωπαίους εταίρους, όπως η Πορτογαλία, η Τουρκία, η Ρουμανία και η Λιθουανία. Η προσπάθεια αυτή ήταν κάτι το μοναδικό για το σχολείο μας, καθώς για πρώτη φορά παιδιά της Πρωτοβάθμιας Eκπαίδευσης όλων των τάξεων θα έπαιρναν μέρος σε κάτι καινούργιο και ξένο προς αυτά αλλά ταυτόχρονα δημιουργικό και ευχάριστο προς αυτό. Πολύ σημαντική ήταν η βοήθεια και η υποστήριξη τόσο του Διευθυντή του Σχολείου καθώς και όλου του εκπαιδευτικού προσωπικού, που συνέβαλε σε αυτή τη μοναδική προσπάθεια, έτσι ώστε να πραγματοποιηθούν όλες οι απαραίτητες δράσεις για την υλοποίηση του προγράμματος. Το κέρδος από αυτό το καινοτόμο πρόγραμμα είναι σημαντικό, καθώς τα παιδιά γνώρισαν και τραγούδησαν παραδοσιακά τραγούδια από την Ελλάδα, άκουσαν τραγούδια άλλων χωρών, ήρθαν σε επικοινωνία με μαθητές από άλλες χώρες, κάτι που θα τους μείνει για πάντα ως μία ευχάριστη εμπειρία στη ζωή τους.
Η εννοιολόγηση και η συμβολοποιήση των γνωστικών πεδίων του μαθητή μέσω της χρήσης πολλάπλων σημειωτικών συστημάτων για την δόμηση επιστημονικού περιεχομένου
Authors: Γεωργακοπούλου Ελένη
Published: December 2023

Η παρούσα διδακτορική διατριβή μελετά τους νοητικούς μηχανισμούς που διαμορφώνουν οι μαθητές/τριες για την κατανόηση των επιστημονικών εννοιών και κατά πόσον τα πολλαπλά σημειωτικά συστήματα διευκολύνουν την αναπαράσταση επιστημονικών εννοιών. Συγκεκριμένα, η εν λόγω ερευνητική μελέτη εστιάζει στον τρόπο με τον οποίο ο μαθητής κατασκευάζει γνωστικά σχήματα μέσω σημειωτικών πόρων, τα οργανώνει σε ένα ευρύτερο νοητικό πλαίσιο και κατασκευάζει γνωστικά πεδία. Επιχειρείται να μελετηθεί ποιος συνδυασμός σημειωτικών συστημάτων είναι πιο αποτελεσματικός από άλλους και με ποια σειρά, ώστε οι μαθητές να κατανοήσουν τις επιστημονικές έννοιες. Η παρούσα μελέτη λαμβάνει υπόψη ότι το προτεινόμενο θεωρητικό μοντέλο μπορεί να εφαρμοστεί σε κάθε θεματικό πεδίο. Με αυτό τον τρόπο φωτίζονται πτυχές της μαθησιακής διαδικασίας, καθώς συνδυάζονται διαφορετικά σημειωτικά συστήματα και καταγράφονται οι διαδικασίες των μαθητών για την κατασκευή της γνώσης. Τα αποτελέσματα της έρευνας δείχνουν ότι: α/ το λεκτικό σύστημα αναπαράστασης παραμένει κυρίαρχο και απαραίτητο για την κατανόηση επιστημονικών εννοιών. Παρόλα αυτά, ο μαθητής φαίνεται να δυσκολεύεται να κατανοεί όλα τα στοιχεία των λεκτικών αναπαραστάσεων στο επίπεδο συνειδητού και συμβολικού, επομένως οι λεκτικές αναπαραστάσεις βοηθούν στην κατανόηση εννοιών αλλά όχι στην ερμηνεία και στην παραγωγή νοήματος. β/ οι οπτικές αναπαραστάσεις βοηθούν τον μαθητή να σχηματοποιήσει τις επιστημονικές έννοιες και να δράσει σε αφηρημένο επίπεδο. Ενισχύουν τις γνωστικές δεξιότητες της κωδικοποίησης, αλλά μόνες τους δεν οικοδομούν νέα γνώση. γ/ οι μαθητές φαίνεται να δυσκολεύονται να προσδιορίσουν τις διαδικασίες που ακολουθούν για να κατανοήσουν τις επιστημονικές έννοιες, δ/ Οι οπτικές αναπαραστάσεις βοηθούν περισσότερο στη διδασκαλία συγκεκριμένων εννοιών και βοηθούν τους μαθητές να αναγνωρίσουν τις γνωστικές διαδικασίες που ακολουθούν. ε/ Οι μαθητές φαίνεται να προτιμούν πρώτα τα οπτικά σημειωτικά συστήματα και μετά τις λεκτικές τους εξηγήσεις ως κείμενα, καθώς οι οπτικοί σημειωτικοί πόροι είναι πιο αφηρημένα σχήματα, αλλά επιτρέπουν στους μαθητές να σκεφτούν πιο βαθιά, καθώς ενεργοποιούν ανώτερες γνωστικές διαδικασίες.