bluuebunny/crossref_metadata_2025 huggingface dataset:
ADP-dependent glucokinase controls metabolic fitness in prostate cancer progression
Authors: Xu Hang , Li Yi-Fan , Yi Xian-Yan-Ling , Zheng Xiao-Nan , Yang Yang , Wang Yan , Liao Da-Zhou , Zhang Jia-Peng , Tan Ping , Xiong Xing-Yu , Jin Xi , Gong Li-Na , Qiu Shi , Cao De-Hong , Li Hong , Wei Qiang , Yang Lu , Ai Jian-Zhong
Published: December 2023

Background

Cell metabolism plays a pivotal role in tumor progression, and targeting cancer metabolism might effectively kill cancer cells. We aimed to investigate the role of hexokinases in prostate cancer (PCa) and identify a crucial target for PCa treatment.

Methods

The Cancer Genome Atlas (TCGA) database, online tools and clinical samples were used to assess the expression and prognostic role of ADP-dependent glucokinase (ADPGK) in PCa. The effect of ADPGK expression on PCa cell malignant phenotypes was validated in vitro and in vivo. Quantitative proteomics, metabolomics, and extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) tests were performed to evaluate the impact of ADPGK on PCa metabolism. The underlying mechanisms were explored through ADPGK overexpression and knockdown, co-immunoprecipitation (Co-IP), ECAR analysis and cell counting kit-8 (CCK-8) assays.

Results

ADPGK was the only glucokinase that was both upregulated and predicted worse overall survival (OS) in prostate adenocarcinoma (PRAD). Clinical sample analysis demonstrated that ADPGK was markedly upregulated in PCa tissues vs. non-PCa tissues. High ADPGK expression indicates worse survival outcomes, and ADPGK serves as an independent factor of biochemical recurrence. In vitro and in vivo experiments showed that ADPGK overexpression promoted PCa cell proliferation and migration, and ADPGK inhibition suppressed malignant phenotypes. Metabolomics, proteomics, and ECAR and OCR tests revealed that ADPGK significantly accelerated glycolysis in PCa. Mechanistically, ADPGK binds aldolase C (ALDOC) to promote glycolysis via AMP-activated protein kinase (AMPK) phosphorylation. ALDOC was positively correlated with ADPGK, and high ALDOC expression was associated with worse survival outcomes in PCa.

Conclusions

In summary, ADPGK is a driving factor in PCa progression, and its high expression contributes to a poor prognosis in PCa patients. ADPGK accelerates PCa glycolysis and progression by activating ALDOC-AMPK signaling, suggesting that ADPGK might be an effective target and marker for PCa treatment and prognosis evaluation.
Upregulation of brain-derived neurotrophic factor by Shiikuwasha (Citrus depressa Hayata)
Authors: Nakajima Kensuke , Okubo Shinya , Ohta Tomoe , Uto Takuhiro , Oiso Shigeru
Published: December 2023

Background

A reduction in the brain-derived neurotrophic factor (BDNF) level in the brain causes depression, whereas an increase in its level has therapeutic benefits against depression. BDNF is synthesized in various peripheral tissues and transported to the brain via the peripheral circulation across the blood–brain barrier. Therefore, substances that upregulate peripheral BDNF level may be used to prevent and treat depression. Previously, we demonstrated thatCitrus unshiupeel (Chinpi) andC. natsudaidaiincreased BDNF level in a human renal adenocarcinoma cell line ACHN, which has BDNF-producing ability. Here, we evaluated whether Shiikuwasha (C. depressaHayata), a citrus species cultivated in East Asia, can upregulate BDNF level in ACHN cells.

Methods

We evaluated the effects of test samples on BDNF production by measuring BDNF level in the medium of ACHN cells after a 24 h cultivation in the presence of test samples. TheBDNFmRNA level was measured by quantitative reverse transcription-polymerase chain reaction, and the phosphorylation level of cyclic adenosine monophosphate response element-binding protein (CREB), a transcription factor regulating BDNF expression, was determined using Western blotting.

Results

We found that methanol extracts of Shiikuwasha peel, pulp, and seed increased the BDNF level in the culture medium of ACHN cells. Shiikuwasha peel and pulp extracts also upregulatedBDNFmRNA level and phosphorylation of CREB.

Conclusions

These results suggest that Shiikuwasha includes the candidate antidepressant substances with peripheral BDNF-upregulation effect.
Dynamic updating of clinical survival prediction models in a changing environment
Authors: Tanner Kamaryn T. , Keogh Ruth H. , Coupland Carol A. C. , Hippisley-Cox Julia , Diaz-Ordaz Karla
Published: December 2023

Background

Over time, the performance of clinical prediction models may deteriorate due to changes in clinical management, data quality, disease risk and/or patient mix. Such prediction models must be updated in order to remain useful. In this study, we investigate dynamic model updating of clinical survival prediction models. In contrast to discrete or one-time updating, dynamic updating refers to a repeated process for updating a prediction model with new data. We aim to extend previous research which focused largely on binary outcome prediction models by concentrating on time-to-event outcomes. We were motivated by the rapidly changing environment seen during the COVID-19 pandemic where mortality rates changed over time and new treatments and vaccines were introduced.

Methods

We illustrate three methods for dynamic model updating: Bayesian dynamic updating, recalibration, and full refitting. We use a simulation study to compare performance in a range of scenarios including changing mortality rates, predictors with low prevalence and the introduction of a new treatment. Next, the updating strategies were applied to a model for predicting 70-day COVID-19-related mortality using patient data from QResearch, an electronic health records database from general practices in the UK.

Results

In simulated scenarios with mortality rates changing over time, all updating methods resulted in better calibration than not updating. Moreover, dynamic updating outperformed ad hoc updating. In the simulation scenario with a new predictor and a small updating dataset, Bayesian updating improved the C-index over not updating and refitting. In the motivating example with a rare outcome, no single updating method offered the best performance.

Conclusions

We found that a dynamic updating process outperformed one-time discrete updating in the simulations. Bayesian updating offered good performance overall, even in scenarios with new predictors and few events. Intercept recalibration was effective in scenarios with smaller sample size and changing baseline hazard. Refitting performance depended on sample size and produced abrupt changes in hazard ratio estimates between periods.
Let’s talk about it: an exploration of the comparative use of three different digital platforms to gather patient-reported outcome measures
Authors: Golden Anna Hundt , Gabriel Meghan Hufstader , Russo Jon , Price Mark , Ruhmel Stephen , Nilsson Ami , Delong Patricia Shepherd , Jelsma Jennifer , Carty Michelle
Published: December 2023

Background

Patient-reported outcome (PRO) measures provide valuable evidence in clinical trials; however, poor compliance with PRO measures is a notable and long-standing problem, resulting in missing data that potentially impact the interpretation of trial results. Interactive, patient-centric platforms may increase participants’ motivation to complete PRO measures over the course of a clinical trial. Thus, the aim of this study was to evaluate and optimize the usability of 3 popular consumer technologies—a traditional app-based interface, a chatbot interface, and a speech-operated interface—that may be used to improve user engagement and compliance with PRO measures.

Methods

Participants aged 18–75 years from the general United States population tested the usability of 3 ePRO platforms: a traditional app-based interface using Datacubed Health Platform (Datacubed), a web-based chatbot interface using the Orbita platform, and a speech-operated Alexa interface using an Alexa Skill called “My Daily Wellness.” The usability of these platforms was tested with 2 PRO measures: the EQ-5D-5 L and the SF-12v2 Health Survey (SF-12v2), Daily recall. Using a crossover design, 3 cohorts of participants tested each ePRO platform daily for 1 week. After testing, interviews were conducted regarding the participants’ experience with each platform.

Results

A total of 24 adults participated in the study. The mean age of participants was 45 years (range, 21–71 years), and half were female (n = 12; 50%). Overall, participants prioritized speed, ease of use, and device portability in selecting their preferred platform. The Datacubed app met these criteria and was the preferred platform among most participants (n = 20; 83%). Participants also suggested various modifications to the platforms, such as programmable notifications, adjustable speed, and additional daily reminders.

Conclusions

These data demonstrate the importance of speed, ease of use, and device portability, features that are currently incorporated in the Datacubed app, in ePRO platforms used in future clinical trials. Additionally, the usability of ePRO platforms may be optimized by adding programmable notifications, adjustable speed, and increased daily reminders. The results of this study may be used to enhance the usability and patient centricity of these platforms to improve user compliance and engagement during clinical trials.
Fuel build-up promotes an increase in fire severity of reburned areas in fire-prone ecosystems of the western Mediterranean Basin
Authors: Fernández-Guisuraga José Manuel , Calvo Leonor
Published: December 2023

Background

Fire-vegetation feedbacks can modulate the global change effects conducive to extreme fire behavior and high fire severity of subsequent wildfires in reburn areas by altering the composition, flammability traits, and spatial arrangement of fuels. Repeated, high-severity wildfires at short return intervals may trigger long-term vegetation state transitions. However, empirical evidence about these feedbacks is absent in fire-prone ecosystems of the western Mediterranean Basin, where the response of fire activity has been enhanced by contemporary socioeconomic and land-use changes. Here, we evaluated whether fire severity differs between initial burns and subsequent wildfires in reburn areas (fire-free periods = 10–15 years) of maritime pine and Aleppo pine forests, holm oak woodlands, and shrublands in the western Mediterranean Basin, and whether there is a relationship between the severity of such interactive wildfire disturbances. We also tested how the type of ecosystem and changes in vegetation structure after the initial wildfires influence these relationships. We leveraged Landsat-based fire severity estimates for initial and last wildfires using the Relativized Burn Ratio (RBR) and Light Detection and Ranging (LiDAR) data acquired before the last wildfire.

Results

Fire severity of the last wildfire was significantly higher than that of the initial wildfire for each dominant ecosystem type in reburn areas. These differences were very pronounced in maritime pine forests and shrublands. For consistency, the same patterns were evidenced for the fire severity in reburn and first-entry areas of the last wildfire for each dominant ecosystem type. Fire severity of the last wildfire in forests and woodlands (particularly maritime pine-dominated) raised with increasing severity of the previous wildfire to a greater extent than in shrublands. Pre-fire fuel density in the lower vegetation strata (up to 4 m high in maritime and Aleppo pine forests, as well as in shrublands, and up to 2 m high in holm oak forests) was significantly higher in reburn than in first-entry areas of the last wildfire.

Conclusions

Our results suggest that land managers should promote more fire-resistant landscapes to high fire severity by minimizing fuel build-up and thus fire hazard through pre-fire fuel reduction treatments such as prescribed burning.
Inflammatory perspectives of polycystic ovary syndrome: role of specific mediators and markers
Authors: Dey Rajen , Bhattacharya Koushik , Basak Asim Kumar , Paul Nimisha , Bandyopadhyay Raktima , Chaudhuri Gargi Ray , Purkait Mahuya Patra , Bhattacharjee Aniruddha , Bose Chaitali , Shukla Nandini , Bhaduri Rama , Roy Soumya Sinha , Syamal Alak Kumar
Published: December 2023

Polycystic ovary syndrome (PCOS) is indeed one of the most common gynecological endocrine disorders, affecting a significant number of females in their reproductive age. While the exact cause of PCOS is not fully understood, several factors are believed to contribute to its onset. The relationship between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation is complex and not fully understood. While there is evidence to suggest an association between PCOS and inflammation, the exact cause and causal nature of this relationship are still under investigation. Several inflammatory markers, including IL-6 (interleukin-6), TNF-α (tumor necrosis factor-alpha), IL-17 (interleukin-17), CRP (C-reactive protein), NLR (neutrophil-to-lymphocyte ratio), and PLR (platelet-to-lymphocyte ratio), have been studied about PCOS. These markers are substances produced by the immune system in response to inflammation. Increased levels of IL-17, IL-1, and IL-8 were correlated with PCO. CRP to albumin ratio can be employed as a precise bio-marker for PCOS. The neutrophil-to-lymphocyte ratio (NLR) indicates poor cardiovascular health and metabolic syndrome (MS) and can be considered a negative regulator for FSH which indirectly stimulates testosterone production. Platelet/lymphocyte ratio (PLR) and mean platelet volume (MPV) are also recently found to be associated with PCOS. The literature explaining the underlying mechanisms with specific inflammatory markers and how inflammation relates to PCOS will be highlighted in this review article. It will also discuss the roles of inflammation and the association of different inflammatory markers in the pathogenesis of PCOS, which may usher in a new era in the treatment approach for PCOS.
Schizophrenia and epigenetics: a comprehensive bibliometric analysis
Authors: Nour El Huda Abd Rahim , Mohd Asyraf Abdull Jalil , Norlelawati A. Talib , Siti Norain Mat Rasid , Wan Muhamad Salahudin Wan Salleh , Norainin Sofiya Azman , Mohamed Bakrim Norbaiyah
Published: December 2023

Background and objective(s)

Numerous studies have explored the association between epigenetics and schizophrenia, yielding various findings and reports. Thus, we conducted a bibliometric analysis of the studies that have investigated this association to provide an overview of the evolution of research on this topic and to determine the current status and areas for advancement in this field.

Methods

We applied several methodologies, such as keyword co-occurrence and co-authorship analysis, to the SCOPUS database to analyze the most significant authors, institutions, and countries and the most cited publications. Several analytic tools were employed, namely Bibliomagika 2.2 and Bibliomagika 1.5 Split for frequency analysis, VOSviewer for data visualization, and Biblioshiny packages from R software to perform the bibliometric analysis.

Results

A total of 397 publications were retrieved, and most were published in 2013, revealing an increasing trend over the past decade. The most productive contributors based on the number of published documents were the Alessandro Guidotti (24 publications), the University of Illinois at Chicago (21 publications), the United States of America (159 publications), and the Journal of Schizophrenia Research (22 publications). The top keywords were schizophrenia (250 occurrences), DNA methylation (174 occurrences), and epigenetics (121 occurrences).

Conclusions

The findings shed light on the research trends, country contributions, influential authors, and most active journals on the topic. This information can help researchers identify gaps and future directions in the field and can provide a platform for progressing knowledge in this field.
A prospective cohort study of severe sepsis-induced dyslipidemia and changes in D-dimer levels in children: do they affect the prognosis?
Authors: Abdelaziz Tarek A. , Mohamed Mohamed Ali Abdou , Ismail Weaam Ibrahim , Idreis Ibrahim Ali Ibrahim , Baz Eman Gamal
Published: December 2023

Background

The dyslipidemia and changes in D-dimer values that occur in children with severe sepsis remain unidentified.

Objective

The current research aimed to explore the relationship between D-dimer and lipid profile values, including total cholesterol (TC), lipoproteins, apolipoprotein A-V (Apo A-5), triglycerides (TG), and in-hospital nonsurvival in children with severe sepsis or septic shock in pediatric intensive care.

Study design

The study design is as follows: prospective cohort study.

Participants

Children with severe sepsis or septic shock who were admitted to the intensive care unit of a university pediatric hospital.

Intervention

Vital signs, sepsis assessment, pediatric sequential organ failure assessment (PSOFA) score, high-density lipoprotein (HDL), Apo A-5, TG, low-density lipoprotein (LDL), TC, D-dimer, mortality outcome, and pediatric risk of mortality (PRISM) III score were evaluated.

Outcomes

The primary outcome was in-hospital nonsurvival.

Results

The nonsurvivors had significantly higher D-dimer levels than the survivors, with a significant cutoff level of 0.87 μg/mL (AUC: 0.85, sensitivity: 93.3%, PVN: 90.6%, accuracy: 79.0%, PVP: 72.5%, and specificity: 64.7%). D-dimer was inversely correlated with WBC count and positively correlated with patient age, PRISM III score, PSOFA score, and INR. However, nonsurvivors had higher TG levels and lower TC, HDL, LDL, and Apo A-5 levels than survivors, but this variation was insignificant. Apo A-5 levels were inversely correlated with HDL and positively correlated with TG levels.

Conclusions

This study suggests that D-dimer is a promising biomarker for severe sepsis in children, with a mortality cutoff level of 0.87 μg/mL. However, lipid profiles are not predictors of sepsis-related mortality.
Moving behavioral interventions in nursing homes from planning to action: a work system evaluation of a urinary tract infection toolkit implementation
Authors: Ford James H. , Nora Anna T. , Crnich Christopher J.
Published: December 2023

Background

Implementation evaluations based on a hybrid deductive-inductive approach provide a detailed understanding of organizational choices to introduce and implement complex interventions and may help explain implementation success or failure. However, such evaluations may not be feasible due to resource constraints. Qualitative analyses of artifacts collected for other purposes during implementation may represent a cost-effective method to understand program implementation when robust evaluations are not feasible. This study used a work systems evaluation of how nursing homes (NHs) implemented a urinary tract infection (UTI) recognition and management improvement toolkit.

Methods

Thirty NHs participated in a randomized control trial in which intervention NHs (n = 12) were assigned a clinical coach who employed a standard template to structure coach calls with the NH champion. A hybrid inductive-deductive approach, using the Systems Engineering Initiative for Patient Safety (SEIPS) model, characterized three action domains related to (1) engagement of staff and providers, (2) distribution of toolkit elements, and (3) toolkit use.

Results

A total of 369 coded segments from 148 coach notes generated by three coaches working with 18 NH champions were examined. Planned changes (n = 203) were more frequent compared to actual changes (n = 169). While most NHs quickly engaged staff and providers, which leadership appeared to support, engagement actions were hindered in some NHs due to champion instability or extended champion or medical director absences. Dissemination of materials to family and providers and distribution of tools to staff occurred quickly in 75% of NHs, although delays were encountered in some NHs, usually because of champion instability.

Conclusions

Implementing NH practice change is challenging, and studies examining actions to support planned versus actual change in this setting are limited. The application of the SEIPS model to coach notes collected during the implementation of a structured behavioral intervention to improve the recognition and management of UTI in NHs generated unique insights into the work system and how staff attempted to implement changes. This study identified several factors that interfered with progression from planning to actual change. Future studies are needed to better understand how to best support change interventions in NHs.

Trial registration

ClinicalTrials.gov, NCT03520010, Registered May 9, 2018.
Data mining twitter for COVID-19 sentiments concerning college online education
Authors: Brandon Daniel
Published: December 2023

In the last decade there has been a large increase in corporate and public reliance on social media for information, rather than on the traditional news and information sources such as print and broadcast media. People freely express their views, moods, activities, likes/dislikes on social media about diverse topics. Rather than surveys and other structured data gathering methods, text data mining is now commonly used by businesses to go through their unstructured text in the form of emails, blogs, tweets, likes, etc. to find out how their customers feel about their company and their products/services. This paper reports upon a study using Twitter (recently renamed to “X”) data to determine if meaningful and actionable information could be gained from such social media data in regard to pandemic issues and how that information compares to a traditional survey. In early 2020, the COVID-19 pandemic hit and forced colleges to move classes to an online format. While there is considerable literature in regard to using social media to communicate geo-political issues and in particular pandemics, there is not a study using social media to explore public sentiment in regard to COVID’s forcing online education upon the public. In this study, text data mining was used to gain some insight into the feeling of Twitter users in regard to the effect of COVID-19 and the switch to online education in colleges. This study found that Twitter data mining did produce actionable information similar to the traditional survey, and the study is important since its results may influence organizations to explore the use of Twitter (and possibly other social media) to obtain people’s sentiments instead of (or in addition to) traditional surveys and other traditional means of gathering such information. This paper demonstrates both the process of text data mining social media and its application to current real-world issues.
Validation of the Indonesian version of the thyroid cancer-specific quality of life as a tool to assess the quality of life among pediatric thyroid cancer patients
Authors: Azhar Yohana , Achmad Dimyati , Rudiman Reno , Candrawinata Valeska Siulinda
Published: December 2023

Background

Diagnosis and management of pediatric cancer develop a major life event that might impact psychosocial functioning and quality of life (QoL) even long after the initial therapy has been completed. Treatment outcomes have been measured in terms of survival time, but they also significantly impact survivors’ quality of life. The pediatric differentiated thyroid carcinoma survivors’ QoL has rarely been evaluated. This study aims to translate and validate the Indonesian version of the ThYCA-QoL questionnaire.

Results

The median age of 105 eligible survivors was 20.88 years old. Eighty percent of the survivors were female, were married or in a relationship (86.7%), and had paid jobs or were full-time students (71.7%). The median follow-up time was 64.82 months. Cronbach-α co-efficient was > 0.70 for psychological, concentration, throat, and mouth problems. For sympathetic, neuromuscular, voice, and sensory, the scores were < 0.70, where a multi-trait scaling analysis showed that all item correlations were > 0.40. Validity was assessed using the Pearson correlation coefficient for y-QoL with r > 0.60 and p < 0.01.

Conclusions

The Indonesian ThYCA-QoL questionnaire is a reliable and valid tool to evaluate pediatric patients’ QoL after treatment. This simple assessment tool can be used to evaluate and manage pediatric thyroid cancer patients’ HRQoL.
The multidimensional benefits of eicosapentaenoic acid: from heart health to inflammatory control
Authors: Nassar Mahmoud , Jaffery Aelia , Ibrahim Bassel , Baraka Bahaaeldin , Abosheaishaa Hazem
Published: December 2023

Eicosapentaenoic acid (EPA) is an omega-3 fatty acid found in fatty fish and fish oil supplements. Over the past few decades, research has suggested that EPA has various potential health benefits, particularly for heart health.

EPA has been associated with reduced inflammation, improved cholesterol levels, and reduced blood pressure, all of which can contribute to a lower risk of heart disease. Additionally, EPA has been found to reduce the risk of blood clots, which can lead to heart attacks and strokes. This comprehensive review article aims to summarize the current state of knowledge regarding the potential health benefits of EPA. We focus on its effects on cardiovascular health, inflammation, atherosclerotic plaques, blood clots, diabetes, obesity, and cancer. Finally, we provide an overview of the recommended daily dose of EPA for optimal health benefits.

This review highlights the importance of EPA in promoting overall health and well-being and provides insights into its potential therapeutic applications.
Trabecular Bone Score as a Marker of Skeletal Fragility Across the Spectrum of Chronic Kidney Disease: A Systematic Review and Meta-analysis
Authors: Bioletto Fabio , Barale Marco , Maiorino Federica , Pusterla Alessia , Fraire Federica , Arvat Emanuela , Ghigo Ezio , Procopio Massimo
Published: December 2023

Context

The impairment of bone microarchitecture is a key determinant of skeletal fragility in patients with chronic kidney disease (CKD). The trabecular bone score (TBS) has been developed as a reliable noninvasive index of bone quality. However, its utility in this setting is still debated.

Objective

The aim of this systematic review and meta-analysis was to summarize the available evidence about TBS as a marker of skeletal fragility across the spectrum of CKD.

Methods

PubMed/Medline, EMBASE, and Cochrane Library databases were systematically searched until July 2023 for studies reporting data about TBS in patients with CKD. Effect sizes were pooled through a random-effect model.

Results

Compared to controls, lower TBS values were observed in CKD patients not on dialysis (−0.057, 95%CI:[−0.090, −0.024], P < .01), in dialysis patients (−0.106, 95%CI:[−0.141, −0.070], P < .01), and in kidney transplant recipients (KTRs) (−0.058, 95%CI:[−0.103, −0.012], P = .01). With respect to fracture risk, TBS was able to predict incident fractures in nondialysis patients at unadjusted analyses (hazard ratio [HR] per SD decrease: 1.45, 95%CI:[1.05, 2.00], P = .02), though only a nonsignificant trend was maintained when fully adjusting the model for FRAX® (HR = 1.26, 95%CI:[0.88, 1.80], P = .21). Dialysis patients with prevalent fractures had lower TBS values compared to unfractured ones (−0.070, 95% CI:[−0.111, −0.028], P < .01). Some studies supported a correlation between TBS and fracture risk in KTRs, but results could not be pooled due to the lack of sufficient data.

Conclusion

CKD patients are characterized by an impairment of bone microarchitecture, as demonstrated by lower TBS values, across the whole spectrum of kidney disease. TBS can also be helpful in the discrimination of fracture risk, with lower values being correlated with a higher risk of prevalent and incident fractures.
Brain Metastases and Leptomeningeal Disease
Authors: Kumthekar Priya , Le Rhun Emilie
Published: December 2023

OBJECTIVE

Central nervous system (CNS) metastases include brain parenchymal, spinal cord, and leptomeningeal metastases. This article discusses the diagnostic and therapeutic advances of the last decade that have improved outcomes for patients with these CNS metastases.

LATEST DEVELOPMENTS

The diagnostic tools for CNS metastases, particularly leptomeningeal disease, have evolved over the past decade with respect to advancements in CSF analysis. Multiple medical therapies are now available for brain metastasis treatment that have shown CNS efficacy, including targeted therapies and antibody-drug conjugates. Molecular testing for CNS metastases has become more common and the repertoire of molecularly targeted therapies continues to expand. Advancements in radiation therapy, including improvements in stereotactic radiation techniques, whole-brain radiation with hippocampal avoidance, and proton beam radiation, have changed the radiation management of patients with CNS metastases. New intrathecal agents are currently being tested for the management of leptomeningeal metastases.

ESSENTIAL POINTS

CNS metastases are far more common than primary brain tumors and are increasing in prevalence in the setting of improved treatments and prolonged survival in patients with systemic cancers. There have been many changes in the diagnostics and treatment of CNS metastases, yielding subsequent improvements in patient outcomes with further advancements on the horizon.
Pediatric Neuro-oncology
Authors: Malbari Fatema
Published: December 2023

Objective

This article reviews the most common pediatric brain tumors, neurocutaneous syndromes, treatment-related neurotoxicities, and the long-term outcomes of survivors.

Latest Developments

In the era of molecular diagnostics, the classification, management, and prognostication of pediatric brain tumors and neurocutaneous syndromes has been refined, resulting in advancements in patient management. Molecular diagnostics have been incorporated into the most recent World Health Organization 2021 classification. This knowledge has allowed for novel therapeutic approaches targeting the biology of these tumors with the intent to improve overall survival, decrease treatment-related morbidity, and improve quality of life. Advances in management have led to better survival, but mortality remains high and significant morbidity persists. Current clinical trials focus on tumor biology targeted therapy, deescalation of therapy, and multimodal intensified approaches with targeted therapy in more high-risk tumors.

Essential Points

Molecular diagnostics for pediatric brain tumors and neurocutaneous syndromes have led to novel therapeutic approaches targeting the biology of these tumors with the goals of improving overall survival and decreasing treatment-related morbidity. Further understanding will lead to continued refinement and improvement of tumor classification, management, and prognostication.
Utopia of the Uniform
Authors: Petrović Tanja
Published: December 2023

The compulsory service for young men in the Yugoslav People’s Army (JNA) created bonds across ethnic, religious, and social lines. These bonds persisted even after the horrific violence of the 1990s, in which many of these men found themselves on opposite sides of the front lines. In Utopia of the Uniform, Tanja Petrovic draws on memories and material effects of dozens of JNA conscripts to show how their experience of military service points to futures, forms of collectivity, and relations between the state and the individual different from those that prevailed in the post-Yugoslav reality. Petrovic argues that the power of repetitive, ritualized, and performative practices that constituted military service in the JNA provided a framework for drastically different men to live together and befriend each other. While Petrovic and her interlocutors do not idealize the JNA, they acknowledge its capacity to create interpersonal relationships and affective bonds that brought the key political ideas of collectivity, solidarity, egalitarianism, education, and comradeship into being.
Bacterial Brain Abscesses Expand Despite Effective Antibiotic Treatment: A Process Powered by Osmosis Due to Neutrophil Cell Death
Authors: Dahlberg Daniel , Holm Sverre , Sagen Ellen Margaret Lund , Michelsen Annika Elisabet , Stensland Maria , de Souza Gustavo Antonio , Müller Ebba Gløersen , Connelly James Patrick , Revheim Mona-Elisabeth , Halvorsen Bente , Hassel Bjørnar
Published: December 2023

BACKGROUND AND OBJECTIVES:

A bacterial brain abscess is an emergency and should be drained of pus within 24 hours of diagnosis, as recently recommended. In this cross-sectional study, we investigated whether delaying pus drainage entails brain abscess expansion and what the underlying mechanism might be.

METHODS:

Repeated brain MRI of 47 patients who did not undergo immediate pus drainage, pus osmolarity measurements, immunocytochemistry, proteomics, and 18F-fluorodeoxyglucose positron emission tomography.

RESULTS:

Time from first to last MRI before neurosurgery was 1 to 14 days. Abscesses expanded in all but 2 patients: The median average increase was 23% per day (range 0%-176%). Abscesses expanded during antibiotic therapy and even if the pus did not contain viable bacteria. In a separate patient cohort, we found that brain abscess pus tended to be hyperosmolar (median value 360 mOsm; range 266-497; n = 14; normal cerebrospinal fluid osmolarity is ∼290 mOsm). Hyperosmolarity would draw water into the abscess cavity, causing abscess expansion in a ballooning manner through increased pressure in the abscess cavity. A mechanism likely underlying pus hyperosmolarity was the recruitment of neutrophils to the abscess cavity with ensuing neutrophil cell death and decomposition of neutrophil proteins and other macromolecules to osmolytes: Pus analysis showed the presence of neutrophil proteins (protein-arginine deiminases, citrullinated histone, myeloperoxidase, elastase, cathelicidin). Previous studies have shown very high levels of osmolytes (ammonia, amino acids) in brain abscess pus. 18F-fluorodeoxyglucose positron emission tomography showed focal neocortical hypometabolism 1 to 8 years after brain abscess, indicating long-lasting damage to brain tissue.

CONCLUSION:

Brain abscesses expand despite effective antibiotic treatment. Furthermore, brain abscesses cause lasting damage to surrounding brain tissue. These findings support drainage of brain abscesses within 24 hours of diagnosis.
Neuroprotective Effects of Artificial Cerebrospinal Fluid: Analysis of Brainstem Auditory–Evoked Potential Monitoring During Microvascular Decompression in 117 Consecutive Patients
Authors: Kobayashi Masahito , Hirata Sachiko , Fujimaki Takamitsu
Published: December 2023

BACKGROUND AND OBJECTIVES:

To study the efficacy of irrigation with artificial cerebrospinal fluid (aCSF) for protection of cranial nerves during surgery; the time required for recovery of brainstem auditory–evoked potentials (BAEPs) that would reflect cochlear function was analyzed in comparison with that for saline irrigation.

METHODS:

This retrospective study included 117 consecutive patients (95 women, mean age 51.5 ± 11.4 year) who underwent microvascular decompression for hemifacial spasm. During surgery, BAEPs were monitored to avoid damage to the auditory pathways. When a delayed latency of >1 ms or a decrease in amplitude of >50% was detected in BAEP wave V, surgical maneuvers were halted, and the operative field was irrigated with saline or aCSF. Saline was used for irrigation in 58 patients and aCSF in the other 59. The time required for BAEP recovery at the first halt in each patient was analyzed, and the results were compared between the groups.

RESULTS:

Surgical procedures were interrupted because of BAEP latency delays or decreases in amplitude in 51 of the patients in the saline group and 54 in the aCSF group. In both groups, the latencies and amplitudes recovered significantly with time and both recovered earlier after aCSF irrigation than after saline irrigation. Hearing outcome was not significantly different between 2 groups.

CONCLUSION:

aCSF is effective for protection of cochlear nerve and promotes recovery from transient dysfunction during surgery. The protective effect may be attributed to multiple factors including conditioned pH, electrolyte composition, glucose, and microelements, such as magnesium and phosphate.
Women Neurosurgeons Worldwide: Characterizing the Global Female Neurosurgical Workforce
Authors: Vaca Silvia D. , Theologitis Marinos , Zygourakis Corinna C.
Published: December 2023

BACKGROUND AND OBJECTIVES:

As the global neurosurgical workforce expands, so do the contributions of women neurosurgeons. Recent studies highlighted pioneering women leaders in neurosurgery and provided invaluable perspectives into the proportion of women neurosurgeons in regions across the world. To provide a broad perspective of global trends, this study aims to characterize the global female neurosurgical workforce and evaluate its association with countries' economic status, broader physician workforce, and global gender gap index (GGGI).

METHODS:

A literature search included studies dated 2016–2023 characterizing the neurosurgical workforce. Total neurosurgeons, neurosurgeons per capita, and percent of women neurosurgeons by country were collected or calculated from available data. Countries were stratified by World Health Organization (WHO) region, World Bank economic classification, WHO physician workforce, and GGGI. Poisson regressions and Spearman correlation tests were performed to evaluate the association between each country's percent of women neurosurgeons and their economic classification, WHO physician workforce, and GGGI.

RESULTS:

Neurosurgical workforce data were obtained for 210 nations; world maps were created demonstrating neurosurgeons per capita and proportion of women neurosurgeons. Africa had the fewest neurosurgeons (1296) yet highest percentage of women neurosurgeons (15%). A total of 94 of 210 (45%) countries met the minimum requirement of neurosurgeons needed to address neurotrauma. Compared with low-income countries, upper-middle–income and high-income countries had 27.5 times greater the rate of neurosurgeons per capita but only 1.02 and 2.57 times greater percentage of women neurosurgeons, respectively (P < .001). There was a statistically significant association between GGI and women neurosurgeons (P < .001) and a weak correlation between proportion of women in physician workforce and women neurosurgeons (P = .019, rho = 0.33).

CONCLUSION:

Much progress has been made in expanding the neurosurgical workforce and the proportion of women within it, but disparities remain. As we address the global neurosurgeon deficit, improving recruitment and retention of women neurosurgeons through mentorship, collaboration, and structural support is essential.
A Randomized Phase III Trial of Complete Mesocolic Excision Compared with Conventional Surgery for Right Colon Cancer: Interim Analysis of a Nationwide Multicenter Study of the Italian Society of Surgical Oncology Colorectal Cancer Network (CoME-in trial)
Authors: Degiuli Maurizio , Aguilar Aridai H. Resendiz , Solej Mario , Azzolina Danila , Marchiori Giulia , Corcione Francesco , Bracale Umberto , Peltrini Roberto , Di Nuzzo Maria M. , Baldazzi Gianandrea , Cassini Diletta , Sica Giuseppe S. , Pirozzi Brunella , Muratore Andrea , Calabrò Marcello , Jovine Elio , Lombardi Raffaele , Anania Gabriele , Chiozza Matteo , Petz Wanda , Pizzini Paolo , Persiani Roberto , Biondi Alberto , Reddavid Rossella
Published: December 2023

Background

Although complete mesocolic excision (CME) is supposed to be associated with a higher lymph node (LN) yield, decreased local recurrence, and survival improvement, its implementation currently is debated because the evidence level of these data is rather low and still not supported by randomized controlled trials.

Method

This is a multicenter, randomized, superiority trial (NCT04871399). The 3-year disease-free survival (DFS) was the primary end point of the study. The secondary end points were safety (duration of operation, perioperative complications, hospital length of stay), oncologic outcomes (number of LNs retrieved, 3- and 5-year overall survival, 5-year DFS), and surgery quality (specimen length, area and integrity rate of mesentery, length of ileocolic and middle-colic vessels). The trial design required the LN yield to be higher in the CME group at interim analysis.

Results

Interim data analysis is presented in this report. The study enrolled 258 patients in nine referral centers. The number of LNs retrieved was significantly higher after CME (25 vs. 20; p = 0.012). No differences were observed with respect to intra- or post-operative complications, postoperative mortality, or duration of surgery. The hospital stay was even shorter after CME (p = 0.039). Quality of surgery indicators were higher in the CME arm of the study. Survival data still were not available.

Conclusions

Interim data show that CME for right colon cancer in referral centers is safe and feasible and does not increase perioperative complications. The study documented with evidence that quality of surgery and LN yield are higher after CME, and this is essential for continuation of patient recruitment and implementation of an optimal comparison.

Trial registration The trial was registered at ClinicalTrials.gov with the code NCT04871399 and with the acronym CoME-In trial.
Intergenerational Mobility in American History: Accounting for Race and Measurement Error
Authors: Ward Zachary
Published: December 2023

A large body of evidence finds that relative mobility in the US has declined over the past 150 years. However, long-run mobility estimates are usually based on White samples and therefore do not account for the limited opportunities available for nonwhite families. Moreover, historical data measure the father’s status with error, which biases estimates toward greater mobility. Using linked census data from 1850 to 1940, I show that accounting for race and measurement error can double estimates of intergenerational persistence. Updated estimates imply that there is greater equality of opportunity today than in the past, mostly because opportunity was never that equal. (JEL J15, J62, N31, N32)
Taking It to the Limit: Effects of Increased Student Loan Availability on Attainment, Earnings, and Financial Well-Being
Authors: Black Sandra E. , Denning Jeffrey T. , Dettling Lisa J. , Goodman Sarena , Turner Lesley J.
Published: December 2023

Growing reliance on student loans and repayment difficulties have raised concerns of a student debt crisis in the United States, but little is known about the effects of student borrowing on human capital and long-run financial well-being. We use variation induced by recent expansions in federal loan limits combined with administrative data-sets to identify the effects of increased access to student loans on credit-constrained students’ educational attainment, earnings, debt, and loan repayment. Increased student loan availability raises student debt and improves degree completion, later-life earnings, and student loan repayment, while having no effect on homeownership or other types of debt. (JEL G51, I22, I23, I26, J24)
Detecting Mother-Father Differences in Spending on Children: A New Approach Using Willingness-to-Pay Elicitation
Authors: Dizon-Ross Rebecca , Jayachandran Seema
Published: December 2023

This paper tests whether mothers and fathers differ in their spending on daughters relative to sons by comparing their willingness to pay (WTP) for specific goods for their children. This method, which we apply in Uganda, offers more precision than the standard method of examining expenditure effects of mothers’ versus fathers’ income. We find that fathers have a lower WTP for their daughters’ than their sons’ human capital but mothers do not. Altruism plays a role: fathers’ but not mothers’ WTP for goods that simply bring joy to their daughters is lower than their WTP for such goods for sons. (JEL D64, G51, J12, J13, J16, O12)
The Global Infrastructure Gap: Potential, Perils, and a Framework for Distinction
Authors: Gardner Camille , Henry Peter Blair
Published: December 2023

In 2015, the World Bank claimed that rich-country private capital could: (i) close the infrastructure services gap in poor countries, (ii) achieve the sustainable development goals, and (iii) make money by moving from “billions to trillions” of investment in poor-country infrastructure. Our framework distinguishes those poor countries in which the Bank’s claim is tenable from those where it is not. For a given poor country, the framework reveals that investing a dollar in infrastructure is efficient if the social rate of return on infrastructure clears two hurdles: (a) the social rate of return on private capital in the poor country, and (b) the social rate of return on private capital in rich countries. Applying the framework to the only comprehensive, cross-country dataset of social rates of return on infrastructure indicates that in 1985 just 7 of 53 poor countries cleared the dual hurdles in both paved roads and electricity. (JEL H43, H54, L94, O13, O18, Q01)
Degree of organ damage and inflammatory markers in sepsis mice models inducted by various doses of lipopolysaccharides
Authors: - Arifin , Purwanto Bambang , Indarto Dono , Wasita Brian , Sumanjar Tatar , Poncorini Eti , - Soetrisno
Published: December 2023

Background Sepsis is a life-threatening disease, and animal models of sepsis are minimal. This study aims to find the optimal dose of LPS to make a sepsis mouse model by examining the presence of target organ damage. Methods This study used 30 mice divided into four groups. The control group (3 mice) injected 0.5 cc NaCl 0.9% intraperitoneally (i.p.). Group A (9 mice) was injected with lipopolysaccharides (LPS) 0.125 mg/kg B.W. i.p. given on the first and second day, group B (9 mice) was injected with LPS 0.15 mg/kg B.W. i.p. given on the first and second days, and group C (9 mice) was injected by LPS 0.3 mg/kg B.W. single dose i.p. On the third, fourth, and fifth days, the termination of each group of three mice and examination of the NF-κB, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), alanine aminotransferase (ALT), the expression of NF-κB in the liver and kidneys, and histopathology in the liver and kidneys were conducted. Results NF-κB, C-reactive protein (CRP), alanine aminotransferase (ALT), NF-κB examinations, and tumor necrosis factor-α (TNF-α) in all treatment groups increased when compared with the control. The highest degree of histopathological features of the kidneys and liver and the results of immunohistochemistry examinations on the liver and kidneys were shown in group C. Conclusions The optimal dose of LPS to make a sepsis mouse model was 0.3 mg/kgB.W with the most severe target organ damage dan significant increased of inflammatory markers.