bluuebunny/crossref_metadata_2025 huggingface dataset:
The miR-6240 target gene Igf2bp3 promotes myoblast fusion by enhancing myomaker mRNA stability
Authors: Huang Yuxin , Wang Wei , Fan Xinhao , Liu Xiaoqin , Liu Weiwei , Wang Zishuai , Li Yixing , Yang Yalan , Tang Zhonglin
Published: December 2024

Background

Myoblast fusion plays a crucial role in myogenesis. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) functions as an RNA N6-methyladenosine reader and exerts important roles in various biological processes. While our prior study suggested Igf2bp3 contributes to myogenesis, its molecular regulatory mechanism is largely unclear.

Methods

Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were used for gene expression analysis. siRNA and CRISPRi technologies were conducted to knockdown the expression of Igf2bp3. CRISPR/Cas9 technology was performed to knockout Igf2bp3. The Igf2bp3 overexpression vector was designed using the pcDNA3.1(+) vector. Immunofluorescence detection was employed for subcellular localization and cell differentiation analysis. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays were conducted for cell proliferation and fusion detection. The dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were utilized for regulatory mechanism analysis of Igf2bp3.

Results

The overexpression of Igf2bp3 enhances myoblast fusion while knockdown of Igf2bp3 blocks the formation of myotubes. miR-6240 promotes myoblast proliferation while preventing myoblast differentiation and fusion by targeting the 3′ untranslated rgion (UTR) of Igf2bp3. Notably, the impacts of miR-6240 mimics on myoblast proliferation, differentiation, and fusion can be effectively counteracted by the overexpression of Igf2bp3. Moreover, our findings elucidate a direct interaction between Igf2bp3 and the myoblast fusion factor myomaker (Mymk). Igf2bp3 binds to Mymk to enhance its mRNA stability. This interaction results in increased expression of Mymk and heightened myoblast fusion.

Conclusions

Our study unveils Igf2bp3 as a novel post-transcriptional regulator of myoblast fusion through the miR-6240/Mymk axis, significantly contributing to our understanding of skeletal muscle development.

Graphical Abstract
Human liver organoids are susceptible to Plasmodium vivax infection
Authors: Nitaramorn Norapat , Kobpornchai Porntida , Tongkrajang Nongnat , Chaisri Urai , Imwong Mallika , Kulkeaw Kasem
Published: December 2024

Background

The eradication of Plasmodium vivax malaria is complicated due to the presence of hypnozoites, the hidden dormant form of the parasite that is present in the liver. Currently available drug regimens are effective at killing hypnozoites but cause side effects and are difficult to administer. Studies testing drugs for liver-stage malaria remain rare and mainly rely on the use of cancerous or immortalized hepatic cells and primary hepatocytes.

Methods

Organoids were used as platform to model liver-stage vivax malaria. Hepatic endoderm cells, endothelial progenitor cells and mesenchymal cells were generated from human induced pluripotent stem cells and self-assembled into liver organoids on top of Matrigel layer. Liver characteristic and maturity were examined through genes and proteins expression of liver markers, and liver functional tests before infected with Plasmodium vivax sporozoites. The infection was then verified by the detection of parasitophorous vacuole membrane proteins, Upregulated in Infectious Sporozoite 4 (UIS4), and blood-stage infection following co-culture with human reticulocytes.

Results

Generated liver organoids showed upregulation of liver specific transcripts including hepatic nuclear factor 4A (HNF4A), alpha-fetoprotein (AFP), and albumin (ALB) which also confirmed by the protein expression. Furthermore, those organoids resembled mature hepatocytes in terms of albumin secretion, fat and glycogen storage and cytochrome activity. Following invasion of P. vivax sporozoites, PvUIS4 was detected and the hepatic merozoites could develop into ring-stage and early trophozoites in human reticulocytes. Moreover, differential expression patterns of genes involved in lipid and cholesterol synthesis were also detected.

Conclusions

Stem cell-derived liver organoids resemble mature liver cells in terms of liver functions and are susceptible to infection with P. vivax sporozoites, paving the way for studies on the mechanism of hypnozoite formation and testing of possible hypnozoitocidal drugs.
Choroid plexus aging: structural and vascular insights from the HCP-aging dataset
Authors: Sun Zhe , Li Chenyang , Zhang Jiangyang , Wisniewski Thomas , Ge Yulin
Published: December 2024

Background

The choroid plexus (ChP), a highly vascularized structure within the ventricles, is essential for cerebrospinal fluid (CSF) production and metabolic waste clearance, crucial for neurofluid homeostasis and cognitive function. ChP enlargement is seen in normal aging and neurodegenerative diseases like Alzheimer’s disease (AD). Despite its key role of in the blood-CSF barrier (BCSFB), detailed studies on age-related changes in its perfusion and microstructure remain limited.

Methods

We analyzed data from 641 healthy individuals aged between 36 and 90, using the Human Connectome Project Aging (HCP-A) dataset. Volumetric, perfusion, and diffusion metrics of the ChP were derived from structural MRI, arterial spin labeling (ASL), and diffusion-weighted imaging (DWI), respectively. Partial correlations were used to explore age-related ChP changes, and independent t-tests to examine sex differences across age decades. One-way ANOVA was employed to compare perfusion characteristics among ChP, gray matter (GM), and white matter (WM). Relationships between volume, perfusion, and diffusion were investigated, adjusting for age and sex. Additionally, the distribution of cyst-like structures within the ChP and their diffusion/perfusion MRI characteristics were analyzed across different age groups.

Results

The ChP undergoes notable changes with age, including an increase in volume (r2 = 0.2, P < 0.001), a decrease in blood flow (r2 = 0.17, P < 0.001), and elevated mean diffusivity (MD) values (r2 = 0.16, P < 0.001). Perfusion characteristics showed significant differences between the ChP, GM, and WM (P < 0.001). Both the ChP and GM exhibited age-related declines in CBF, with a more pronounced decline in the ChP. A negative correlation was observed between the age-related increase in ChP volume and the decrease in CBF, suggesting compensatory dystrophic hyperplasia in response to perfusion decline. Cyst-like structures in ChP, characterized by lower MD and reduced CBF, were found to be more prevalent in older individuals.

Conclusions

Our findings provide a detailed quantitative assessment of age-related changes in ChP perfusion and diffusion, which may affect CSF production and circulation, potentially leading to waste solute accumulation and cognitive impairment.

Grant support

This work was supported in part by the NIH U01AG052564, P30AG066512, P01AG060882, RF1 NS110041, R01 NS108491, U24 NS135568.
Development and validation of a model based on preoperative dual-layer detector spectral computed tomography 3D VOI-based quantitative parameters to predict high Ki-67 proliferation index in pancreatic ductal adenocarcinoma
Authors: Zeng Dan , Zhang Jiayan , Song Zuhua , Li Qian , Zhang Dan , Li Xiaojiao , Wen Youjia , Ren Xiaofang , Wang Xinwei , Zhang Xiaodi , Tang Zhuoyue
Published: December 2024

Objective

To develop and validate a model integrating dual-layer detector spectral computed tomography (DLCT) three-dimensional (3D) volume of interest (VOI)-based quantitative parameters and clinical features for predicting Ki-67 proliferation index (PI) in pancreatic ductal adenocarcinoma (PDAC).

Materials and methods

A total of 162 patients with histopathologically confirmed PDAC who underwent DLCT examination were included and allocated to the training (114) and validation (48) sets. 3D VOI-iodine concentration (IC), 3D VOI-slope of the spectral attenuation curves, and 3D VOI-effective atomic number were obtained from the portal venous phase. The significant clinical features and DLCT quantitative parameters were identified through univariate analysis and multivariate logistic regression. The discrimination capability and clinical applicability of the clinical, DLCT, and DLCT-clinical models were quantified by the Receiver Operating Characteristic curve (ROC) and Decision Curve Analysis (DCA), respectively. The optimal model was then used to develop a nomogram, with the goodness-of-fit evaluated through the calibration curve.

Results

The DLCT-clinical model demonstrated superior predictive capability and a satisfactory net benefit for Ki-67 PI in PDAC compared to the clinical and DLCT models. The DLCT-clinical model integrating 3D VOI-IC and CA125 showed area under the ROC curves of 0.939 (95% CI, 0.895–0.982) and 0.915 (95% CI, 0.834–0.996) in the training and validation sets, respectively. The nomogram derived from the DLCT-clinical model exhibited favorable calibration, as depicted by the calibration curve.

Conclusions

The proposed model based on DLCT 3D VOI-IC and CA125 is a non-invasive and effective preoperative prediction tool demonstrating favorable predictive performance for Ki-67 PI in PDAC.

Critical relevance statement

The dual-layer detector spectral computed tomography-clinical model could help predict high Ki-67 PI in pancreatic ductal adenocarcinoma patients, which may help clinicians provide appropriate and individualized treatments.

Key Points

Dual-layer detector spectral CT (DLCT) could predict Ki-67 in pancreatic ductal adenocarcinoma (PDAC).

The DLCT-clinical model improved the differential diagnosis of Ki-67.

The nomogram showed satisfactory calibration and net benefit for discriminating Ki-67.

Graphical Abstract
MRI analysis of relative tumor enhancement in liver metastases and correlation with immunohistochemical features
Authors: Barajas Ordonez Felix , Gottschling Sebastian , Eger Kai Ina , Borggrefe Jan , Jechorek Dörthe , Surov Alexey
Published: December 2024

Objective

Investigate the association between the relative tumor enhancement (RTE) of gadoxetic acid across various MRI phases and immunohistochemical (IHC) features in patients with liver metastases (LM) from colorectal cancer (CRC), breast cancer (BC), and pancreatic cancer (PC).

Methods

A retrospective analysis was conducted on 68 patients with LM who underwent 1.5-T MRI scans. Non-contrast and contrast-enhanced T1-weighted (T1-w) gradient echo (GRE) sequences were acquired before LM biopsy. RTE values among LM groups were compared by cancer type using analysis of variance. The relationships between RTE and IHC features tumor stroma ratio, cell count, Ki67 proliferation index, and CD45 expression were evaluated using Spearman’s rank correlation coefficients.

Results

Significant differences in RTE were observed across different MRI phases among patients with BCLM, CRCLM, and PCLM: arterial phase (0.75 ± 0.42, 0.37 ± 0.36, and 0.44 ± 0.19), portal venous phase (1.09 ± 0.41, 0.59 ± 0.44, and 0.53 ± 0.24), and venous phase (1.11 ± 0.45, 0.65 ± 0.61, and 0.50 ± 0.20). In CRCLM, RTE inversely correlated with mean Ki67 (r = −0.50, p = 0.01) in the hepatobiliary phase. Negative correlations between RTE and CD45 expression were found in PCLM and CRCLM in the portal venous phase (r = −0.69, p = 0.01 and r = −0.41, p = 0.04) and the venous phase (r = −0.65, p = 0.01 and r = −0.44, p = 0.02).

Conclusion

Significant variations in RTE were identified among different types of LM, with correlations between RTE values and IHC markers such as CD45 and Ki67 suggesting that RTE may serve as a non-invasive biomarker for predicting IHC features in LM.

Critical relevance statement

RTE values serve as a predictive biomarker for IHC features in liver metastasis, potentially enhancing non-invasive patient assessment, disease monitoring, and treatment planning.

Key Points

Few studies link gadoxetic acid-enhanced MRI with immunohistochemistry in LM.

RTE varies by liver metastasis type and correlates with CD45 and Ki67.

RTE reflects IHC features in LM, aiding non-invasive assessment.

Graphical Abstract
Enablers to high vaccination uptake among a disadvantaged minority population: a qualitative study of the Arab population of Israel
Authors: Essa-Hadad Jumanah , Jansen Danielle E.M.C. , Vervoort Johanna P.M. , Edelstein Michael
Published: December 2024

Background

Over 1.9 million Arabs live in Israel and constitute 21% of the total population. Despite being a disadvantaged minority population with wide gaps in health indicators, Arabs have higher Human Papillomavirus (HPV) and Measles, Mumps, and Rubella (MMR) vaccination rates compared with the general Jewish population.

Methods

In-depth interviews with 21 health care providers, 16 Arab mothers, and 16 teenagers were conducted to collect information about health system enablers to HPV and MMR vaccination. All interviews were conducted in Arabic by an Arab researcher, audio-recorded, transcribed, and analysed using thematic analysis of the transcripts. Themes were mapped according to the WHO Health Systems Building Block Framework.

Results

We identified several health system enablers. On the service delivery level, accessible and availability of vaccination services, delivery of vaccines through the school system and mother child clinics, and framing vaccinations as the norm were themes. Personable characteristics of the health workforce, the health care providers belonging to the same cultural group, and high levels of trust towards healthcare professionals were reported. Vaccination provided at no cost was also identified. On the leadership/governance level, the Arab community felt equal treatment and distribution of services, which was also an enabler reported. Despite high vaccine uptakes, parents and teenagers had limited knowledge regarding vaccination, particularly HPV.

Conclusions

This study highlights that a combination of good access and delivery to vaccination, delivered by a culturally competent, available, accessible respectful workforce can enable disadvantaged minorities to achieve high vaccine coverage, in particular in a cultural context where the population trusts and follows medical advice. Such evidence can serve as a basis for developing policies, interventions, and guidance to improve vaccine uptake among other underserved minority communities.
Digital nudging at the university canteen: an online study with American young adults
Authors: Andreani Giulia , Wongprawmas Rungsaran , Biasini Beatrice , Rosi Alice , Franchini Cinzia , Dolgopolova Irina , Mora Cristina , Menozzi Davide , Scazzina Francesca , Gómez Miguel I. , Roosen Jutta , Sogari Giovanni
Published: December 2024

Resource scarcity, the effects of climate change, food insecurity, and health issues related to dietary choices have prompted policymakers to develop new strategies to encourage populations to opt for healthy and sustainable (HS) diets. In this context, nudging strategies are promising tools to promote healthy and sustainable dietary behaviors. However, nudges are context-dependent as a specific nudging intervention should be employed in a specific context. This research aims at determining the effects of different nudges on students’ food choices in the context of a hypothetical online pre-ordering system of the college canteen. An experimental study was conducted in the USA with 1400 American college students (18–24 years old). We used a between-subject design with one control and three treatment groups—i.e., a HS logo to identify HS dishes, dish placement (the order in which dishes are displayed on the menu), and a combination of the two nudges. Our main results showed that the logo and logo plus placement led to a significantly increased selection of HS dishes among students who already had strong HS eating behaviors. In addition, individual characteristics (e.g., being flexitarian or vegetarian, being on a low-calorie diet, being a graduate student, and living in dormitories on college campuses) also affected their HS food choices; thus, the population traits, living conditions, and eating habits should be taken into consideration in order to establish successful nudging techniques.
Invisible walls? Stigma-related perceptions are associated with reduced help-seeking intentions for disordered eating in men
Authors: Lehe Martin S. , Halbeisen Georg , Steins-Loeber Sabine , Paslakis Georgios
Published: December 2024

Background

Eating disorders (EDs) are increasingly prevalent in men, but men remain underrepresented across many ED-specific treatment settings. Based on the idea that persistent stereotypes, prejudice and discrimination, i.e., stigma against men with EDs, could impede help-seeking behaviors, the present study investigated whether stigma-related perceptions in men are associated with reduced help-seeking intentions for a broad range of disordered eating symptoms.

Methods

N = 132 adult men participated in a cross-sectional online survey and completed questionnaires on ED psychopathology, muscle dysmorphia, orthorexic eating, stigma-related perceptions of EDs in men, and help-seeking intentions.

Results

Moderator analyses showed that higher stigma-related perceptions were associated with reduced help-seeking intentions in response to increased ED symptom severity. However, this was only the case for traditionally “feminized” ED symptoms (related to thin-body ideals), but not for help-seeking with regard to muscularity-oriented, orthorexic, or avoidant/restrictive disordered eating.

Conclusions

Stigma may reduce help-seeking intentions with regard to “feminized” ED symptoms. The present findings suggest that perceptions of EDs as “women’s diseases” were associated with reduced help-seeking in men. Stigma towards men with EDs could thus be a possible barrier to help-seeking in men, highlighting the relevance of stigma-reducing interventions in clinical and community settings.
Pattern and driver of Rosa roxburghii Tratt suitability and its effect on ecological services in karst desertification control areas
Authors: Min Xiaoying , Zhang Shihao , Xiong Kangning , Wang Lin , Yang Qingxiong
Published: December 2024

The eco-industry is an effective path to achieve ecological and economic sustainable development. However, the role played by Rosa roxburghii Tratt (R. roxburghii) industry in karst desertification control still needs to be determined. In this study, we predict the suitability probability and driving variables of R. roxburghii's distribution through a Maximum Entropy model, combining climate, population, vegetation, and soil data, and conducted a sample plot survey in a high-suitability area to explore the role of the R. roxburghii industry in ecological services by using adjacent non-R. roxburghii patches as comparisons. The results showed that South China Karst, with its simultaneous rain and heat climate characteristics, was the most suitable area for the industrialization of R. roxburghii in the world. In South China Karst, the area of no, low, medium, and high suitability zones for R. roxburghii was 4.2 × 105, 6.12 × 105, 4.64 × 105, and 4.42 × 105 km2, respectively, and population distribution was the dominant variable controlling its distribution. The net primary productivity, soil conservation, water conservation, mean species abundance, and aboveground biomass of the R. roxburghii monoculture plot in the high-suitability area were significantly lower than those of adjacent non-R. roxburghii lands and forest patches. Furthermore, the monoculture had higher trade-offs between provision, regulation, and support service. This study found that the monoculture of R. roxburghii industry, dominated by human activities, failed to improve ecological services and exacerbated the trade-offs between services. Therefore, future karst desertification control still needs to follow the agroforestry development path.
Spatial structures of blue low-latitude aurora observed from Japan during the extreme geomagnetic storm of May 2024
Authors: Nanjo Sota , Shiokawa Kazuo
Published: December 2024

On May 11, 2024, an extreme G5-class geomagnetic storm triggered a spectacular and unusual display of colorful auroras in mid- to low-latitude regions all over the world. In Japan, auroras were seen not only from Hokkaido, the northernmost island, but also from the northern and central parts of Honshu, the main island. The widespread availability of commercial digital cameras among the public led to a flooding of high-resolution auroral images on social media. This study reports on the appearance of a blue-dominant aurora during a storm-time substorm on this day and its magnetic field-aligned and longitudinal structures captured by citizen scientists. Observations from two photographers at different locations revealed that the aurora was located at approximately 40 degrees magnetic latitude and magnetic local time (MLT) of 23 h, spanned about 1200 km (1-h MLT) in the longitudinal direction with three separated structures, and ranged in altitude from 400 km to at least 900 km. Simultaneous photometric measurements suggested that this blue-dominant aurora likely included emissions at 427.8 nm. While previous studies have noted the existence of emissions at 427.8 nm in low-latitude auroras, this is the first time that a blue-dominant low-latitude aurora has been spatially identified and shown to have longitudinal and field-aligned structures. Additionally, previous studies suggested that blue emissions in low-latitude auroras are produced by energetic neutral atoms from the ring current. However, identifying longitudinal and field-aligned structures in this study may need an alternative explanation.

Graphical Abstract
Can heart rate sequences from wearable devices predict day-long mental states in higher education students: a signal processing and machine learning case study at a UK university
Authors: Chen Tianhua
Published: December 2024

The mental health of students in higher education has been a growing concern, with increasing evidence pointing to heightened risks of developing mental health condition. This research aims to explore whether day-long heart rate sequences, collected continuously through Apple Watch in an open environment without restrictions on daily routines, can effectively indicate mental states, particularly stress for university students. While heart rate (HR) is commonly used to monitor physical activity or responses to isolated stimuli in a controlled setting, such as stress-inducing tests, this study addresses the gap by analyzing heart rate fluctuations throughout a day, examining their potential to gauge overall stress levels in a more comprehensive and real-world context. The data for this research was collected at a public university in the UK. Using signal processing, both original heart rate sequences and their representations, via Fourier transformation and wavelet analysis, have been modeled using advanced machine learning algorithms. Having achieving statistically significant results over the baseline, this provides a understanding of how heart rate sequences alone may be used to characterize mental states through signal processing and machine learning, with the system poised for further testing as the ongoing data collection continues.
Advancement in UV-Visible-IR camouflage textiles for concealment of defence surveillance against multidimensional combat backgrounds
Authors: Hossain Md. Anowar
Published: December 2024

Target detection of defence technologies is being rapidly upgraded with modern surveillance technologies. The latest techniques of surveillance are already being implemented for defence applications. Self-protection and hiding from opposing forces are the key principles for the protection of special team in defence. Camouflage textiles aim to create confusing objects for target detection of military personnel. These textiles are applied for military protection such as clothing, weapons, vehicles and location hiding nets/tents. The urgent need for camouflage textiles has been formulated with a technical solution and implementation of the right camouflage materials for concealment of defence target signature against dry leaves, green leaves and tree bark-woodland combat background; water-marine combat background; sand-desertland combat background; stone-stoneland combat background; snow-snowland combat background; sky combat background; ice-iceland combat background; and concrete-concreteland combat background (DGTWSICB) in ultraviolet–visible-infrared (UV–Vis-IR) spectrums. This hypothesis of optical and surveillance engineering, digital imaging and hyperspectral imaging has been coalesced for the advancement of UV–Vis-IR-DGTWSICB camouflage textile technology. The principle of camouflage engineering has been approached by broader spectrum probes in UV–Vis-IR rather than Vis ranges only. Furthermore, camouflage materials, camouflage weapon designs, and formulations of camouflage textiles have been proposed for multidimensional CBs-DGTWSICB. The electromagnetic spectrum, reflection, electron energy, photonic signal and imaging mechanism in UV–Vis-IR have been presented for optical engineering of concealment, detection, recognition and identification of target signature against DGTWSICB. The spectrum relationship of camouflage materials and DGTWSICB materials has been illustrated and compared in UV–Vis-IR spectrums. Camouflage material design, method design and spectral design; textile colorants and technologies; adaptive camouflage; techniques for camouflage textile assessment for digital camera and hyperspectral camera imaging; image processing techniques; and a hierarchical model have been demonstrated for augmentation of camouflage textiles in UV–Vis-IR illumination. Therefore, the anticipated design of camouflage textiles may enhance high-performance innovation for modern surveillance of military protection related to digital camera, hyperspectral camera and radar. This hypothesis includes advanced guidelines for the advanced design of camouflage textiles for multidimensional CBs-DGTWSICB. The challenges, limitations, innovation and defence applications of camouflage engineering for multidimensional combat backgrounds have been coalesced for concealment, detection, recognition and identification of defence target signature.
INDEPSO-ISPSM Consensus on Peritoneal Malignancies: Management of Colorectal Peritoneal Metastases
Authors: Patel Swapnil , Sheshadri Ramakrishnan Ayloor , Saklani Avanish , SP Somashekhar , Kumar Rohit , Singh Shivendra , Sukumar Vivek , Bhatt Aditi
Published: December 2024

PURPOSE

This manuscript reports the results of the Indian Network for Development of Peritoneal Surface Oncology and Indian Society of Peritoneal Surface Malignancies (INDEPSO-ISPSM) consensus that aimed to provide recommendations for some important aspects management of patients with colorectal peritoneal metastases (CPM) and address some issues unique to India.

METHODS

The modified Delphi technique was used with two rounds of voting. There were 29 questions on nine main topics—the role of cytoreductive surgery (CRS), patient selection for CRS, preoperative workup, role of systemic chemotherapy (SC), CPM with other visceral metastases, molecular profile, hyperthermic intraperitoneal chemotherapy (HIPEC) and other modalities of intraperitoneal chemotherapy (IPC), prophylactic/preventive strategies, and surveillances after CRS. A consensus was achieved if anyone option received >70 votes (strong consensus >90%).

RESULTS

Forty-eight surgical (n = 41) and gastrointestinal (n = 7) oncologists were invited; 44 agreed to participate. The response rate was 95.4% (42/44) in round 1 and 93.1% (41/44) in round 2. Overall, a consensus was achieved on 23/29 (79.3%) questions (strong consensus on 6/29 [20.6%]). The panel strongly recommended considering surgery for limited CPM with limited liver metastases (92.5%), not altering the surgical approach in patients with
KRAS
mutations (91.67%), and limiting the use of IPC for unresectable CPM outside clinical trials (95%). Adjuvant SC was recommended for all patients undergoing CRS (89.47%). CRS is a therapeutic option for selected patients with CPM including those with metachronous CPM (79.49) and signet ring cell cancers (76.92%). HIPEC was recommended outside clinical trials only for patients with peritoneal cancer index 11-15(80%).

CONCLUSION

The panel recommended CRS for most indications but was very selective in recommending HIPEC and IPC outside clinical trials. These recommendations should be a useful resource in clinical decision making for clinicians treating CPM in India and regions with a similar sociodemographic background.
Clinical and Preclinical Activity of EGFR Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer Harboring
BRAF
Class 3 Mutations
Authors: Di Federico Alessandro , Angelicola Stefania , Frascino Mariateresa , Siracusa Irene , Bisanti Beatrice , Ruzzi Francesca , Semprini Maria Sofia , De Jonge Hugo , De Giglio Andrea , Sperandi Francesca , Brocchi Stefano , Melotti Barbara , Giunchi Francesca , Gruppioni Elisa , Altimari Annalisa , Lollini Pier-Luigi , Ardizzoni Andrea , Palladini Arianna , Gelsomino Francesco
Published: December 2024

PURPOSE

Patients with tumors harboring
BRAF
class 3 mutations lack targeted therapies. These mutations are characterized by low/absent BRAF kinase domain activation and are believed to amplify already active RAS signaling, potentially triggered by receptor tyrosine kinases like EGFR.

MATERIALS AND METHODS

Two patients with
BRAF
class 3–mutated metastatic non–small-cell lung cancer (NSCLC) were treated with erlotinib at our Institution after failure of standard therapies. Two cell lines were established from patients with
BRAF
class 3–mutated NSCLC, and their sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKIs) was assessed using
EGFR-
mutated,
BRAF
class 1 and 2–mutated, and
KRAS
-mutated NSCLC cell lines as controls.

RESULTS

Patient 1, a 60-year-old male with BRAF
D594N
-mutated NSCLC, achieved complete response to erlotinib after progression on first- and second-line chemotherapy. Patient 2, a 60-year-old female with BRAF
D594G
-mutated NSCLC, achieved partial response to erlotinib after progression on first-line chemoimmunotherapy. High baseline phosphorylated EGFR values and reduced EGFR activation following erlotinib were observed in
BRAF
class 3–mutated and
EGFR
-mutated cell lines, but not in
BRAF
class 1–mutated,
BRAF
class 2–mutated, or
KRAS
-mutated lines. Erlotinib inhibited 2-dimensional growth in
BRAF
class 3–mutated cell lines (IC
50
6.33 and 7.11 µM) and in the
BRAF
class 2–mutated cell line (IC
50
5.51 µM), albeit at higher concentrations than in
EGFR
-mutated lines, whereas it showed no effect on
BRAF
class 1–mutated (IC
50
, >25 µM) or
KRAS
-mutated (IC
50
, >25 µM) lines. These findings were corroborated by 3-dimensional and sphere formation assays. In the Cancer Cell Line Encyclopedia,
BRAF
class 3–mutated NSCLC cell lines showed greater sensitivity to EGFR-TKIs compared with
BRAF
class 2–mutated and
KRAS
-mutated lines.

CONCLUSION

BRAF
class 3 mutations in NSCLC may identify a novel targetable population sensitive to EGFR-TKIs.
Ethnic Differences in Characteristics of Women Diagnosed With Early Gestational Diabetes: Findings From the TOBOGM Study
Authors: Yuen Lili , Wong Vincent , Immanuel Jincy , Hague William M , Cheung N Wah , Teede Helena , Hibbert Emily , Nolan Christopher J , Peek Michael , Flack Jeff R , McLean Mark , Sweeting Arianne , Kautzky-Willer Alexandra , Harreiter Jürgen , Gianatti Emily , Mohan Viswanathan , Backman Helena , Simmons David
Published: December 2024

Objective

To compare the prevalence and clinical characteristics of early gestational diabetes (eGDM) and associated birth outcomes among women of different ethnic groups.

Methods

This is a secondary analysis of an international, multicenter randomized controlled trial of treating eGDM among pregnant women with GDM risk factors enrolled at < 20 weeks’ gestation. GDM diagnosis was made using WHO-2013 criteria. Ethnicity was classified by self-identification. While Europids required at least one risk factor for recruitment, for others, ethnicity itself was a risk factor.

Results

Among women of Europid (n = 1567), South Asian (SA: n = 971), East and South-East Asian (ESEA: n = 498), Middle Eastern (ME: n = 242), and Māori and Pasifika (MP: n = 174) ethnicities; MP (26.4%) had the highest eGDM crude prevalence compared with Europid (20.3%), SA (24.7%), ESEA (22.3%), and ME (21.1%) (P < .001). Compared with Europid, the highest eGDM adjusted odds ratio (aOR) was seen in SA (2.43 [95% CI 1.9-3.11]) and ESEA (aOR 2.28 [95% CI 1.68-3.08]); in late GDM, SA had the highest prevalence (20.4%: aOR 2.16 [95% CI 1.61-2.9]). Glucose patterns varied between ethnic groups and ESEA were predominantly diagnosed with eGDM through post-glucose load values, while all other ethnic groups were mainly diagnosed on fasting glucose values. There were no differences in the eGDM composite primary outcome or neonatal and pregnancy-related hypertension outcomes between the ethnic groups.

Conclusion

In women with risk factors, eGDM was most prevalent in SA and ESEA women, particularly identified by the post-glucose load samples. These findings suggest an early oral glucose tolerance test should particularly be performed in women from these ethnic groups.
The Causal Effect of Increasing Area-Level Income on Birth Outcomes and Pregnancy-Related Health: Estimates From the Marcellus Shale Boom Economy
Authors: Martin Molly A. , Green Tiffany L. , Chapman Alexander
Published: December 2024

Income is positively correlated with pregnancy health and birth outcomes, but the causal evidence for this association is limited. Leveraging a natural experiment based on the Pennsylvania boom economy created by the extraction of natural gas from the Marcellus Shale geological formation, we test whether area-level income gains impact birth outcomes (birth weight, gestational length, and preterm birth) and pregnancy health (prepregnancy and prenatal smoking, prepregnancy weight status, gestational weight gain, and the timing and adequacy of prenatal care). We append tax data to birth certificate data and compare health outcomes before and after the boom for births occurring in school districts above the Marcellus Shale. We also explore income effects with a subsample of siblings and test for nonlinear income effects by considering preboom district poverty rates. Using instrumented difference-in-differences models, we find that plausibly exogenous income gains increase the likelihood of having adequate prenatal care in the full sample. In the sibling sample, income gains decrease the likelihood of low birth weight but increase the likelihood of prepregnancy underweight among birthing parents. Results are statistically significant in initially high-poverty districts. We thus affirm prior findings of a causal effect of income on birth weight and prenatal care use but find minimal area-level income effects on other pregnancy-related health behaviors and birth outcomes.
Should They Compete or Should They Cooperate? The View of Agency Theory
Authors: Fleckinger Pierre , Martimort David , Roux Nicolas
Published: December 2024

What is the most efficient way of designing incentives in an organization? Over the past five decades, agency theory has provided various answers to this crucial question. This line of research suggests that, depending on the organizational context, the optimal approach to providing incentives may involve either relying on collective compensations or, conversely, employing relative performance evaluations. In the first scenario, cooperation among agents is the key aspect of the organization. In the second, competition prevails. This paper provides a comprehensive overview of this extensive literature with the aim of understanding the conditions under which one or the other type of incentive schemes is more desirable for the principal of the organization. To this end, we use a flexible and versatile model capable of addressing a wide range of scenarios characterized by different technologies, information constraints, and behavioral norms. ( JEL C70, D62, D82, D83, D86, L12, M54)
Soviet Mathematics and Economic Theory in the Past Century: A Historical Reappraisal
Authors: Boldyrev Ivan
Published: December 2024

What are the effects of authoritarian regimes on scholarly research in economics? And how might economic theory survive ideological pressures? This article addresses these questions by focusing on the mathematization of economics over the past century and drawing on the history of Soviet science. Mathematics in the USSR remained internationally competitive and generated many ideas that were taken up and played important roles in economic theory. These same ideas, however, were disregarded or adopted only in piecemeal fashion by Soviet economists, despite the efforts of influential scholars to change the economic research agenda. The article draws this contrast into sharper focus by exploring the work of Soviet mathematicians in optimization, game theory, and probability theory that was used in Western economics. While the intellectual exchange across the Iron Curtain did help advance the formal modeling apparatus, economics could only thrive in an intellectually open environment absent under Soviet rule. (JEL B23, B24, B30, C02)
The Divine Economy: How Religions Compete for Wealth, Power, and People
Authors: Becker Sascha O.
Published: December 2024

Sascha O. Becker of Monash University and University of Warwick reviews “The Divine Economy: How Religions Compete for Wealth, Power, and People” by Paul Seabright. The Econlit abstract of this book begins: “Presents a platform model of religious movements, discussing how the competition for members and resources between such movements shapes what is possible for them and their political backers.”
The Awareness of Dental Erosion and Its Causes and Protective Factors Among a General Adult Population of Trinidad and Tobago
Authors: Marchan Shivaughn , Johnson Tenille , Cumberbatch Anamia , Hinds Zari , Joseph Keanna , Coldero Larry
Published: December 2024

Introduction Given the worldwide prevalence of tooth wear and wear related to dental erosion a baseline understanding of the knowledge of populations related to erosive wear is required to maximize public health campaigns developed to address this condition. This research investigated the awareness of dental erosion, its causes, and protective factors among the general adult population of Trinidad and Tobago. Methods An anonymous de-novo questionnaire, developed using Google Forms and aligned with the CHERRIES framework for web-based surveys, was subjected to face validity to ensure the inclusion of content relevant to erosive tooth wear and clarity of items intended for a general population. The questionnaire was deployed on social media platforms (Facebook) and groups (WhatsApp Community Groups) specific to groups in Trinidad and Tobago for four months. Data was entered into SPSS (Version 29) and analyzed using cross-tabulations and Chi-squared tests. Results Of the 210 respondents, 39.2% had previously been diagnosed with tooth wear, 43.1 % believed they could identify erosive wear and 42.1% believed they could differentiate between predominantly erosive wear and dental caries. Sixty-two point nine percent of respondents identified sensitivity as a symptom of erosive tooth wear. Chi-squared tests on cross-tabulated data showed significant relationships between age and GERD causing erosive wear (p=0.03), heartburn causing erosive wear (p=0.049), eating disorders causing erosive wear (p=0.009), disorders with excessive vomiting causing erosive wear (p=0.005), excessive wine consumption (p=0.004). There were no significant statistical significances for cross-tabulated data on sex and the responses on causative factors. Conclusions Respondents were generally knowledgeable about the various types of foods, beverages, and medical conditions that may cause dental erosion but were unfamiliar with other factors that may influence erosion or protect against dental erosion.
Network and sentiment analysis of Enron emails
Authors: Belay Natnael
Published: December 2024

Background The objective of the research was to analyze e-mails exchanged at Enron, a power company that declared bankruptcy in 2001 following an investigation into unethical operations regarding their financials. Methods Like other researchers, we identify the “most important” employees and detect “communities” using network science methods. In addition, because previous work required that 10 e-mails be sent and received for an e-mail relationship to exist, we analyzed the effect of different “thresholds” on the results. We also performed sentiment analyses on the e-mails to evaluate whether sentiment changed over time. Results We find that the “importance” of a person depends on the centrality measure used; while the communities we detected resembled the formal organizational structure of the company. In addition, we found that centrality results were very dependent on the “threshold” used. Finally, analysis of email sentiment over time = do not give insight into the financial wellbeing of Enron. Conclusion Our results provide insight into how information flowed through Enron, who the key employees were, and e-mail sentiment before and after the crisis.
High-performance large-area terahertz detector based on the WTe2 film of Weyl semimetal with a subwavelength zigzag line array
Authors: Wang Yifei , Jia Erse , Peng Zhongze , Chen Run , Chai Lu , Hu Minglie
Published: December 2024

A large-area terahertz detector based on a subwavelength zigzag line array on the Weyl semimetal film of WTe2 was designed and prepared. A high-performance device, on account of the combination of the absorption characteristic of Weyl semimetals for long-wave photons with low energy and the enhancement effect of the localized surface plasmon by virtue of a subwavelength zigzag line array structure, has been demonstrated by a numerical simulation and experimental verification. A high-performance detection ability of a large 3.8 mm square area for a 0.1 THz wave at room temperature was verified. The characteristic parameters of the detection ability for the device with a 70 µm line width of WTe2 under the bias voltage of 20 V were obtained with a photocurrent responsivity (R
i
) of 9.51mAW−1, a noise equivalent power (NEP) of 89.3pWHz−1/2, and a detectivity (D∗) of 4.25×109cmHz1/2W−1.
Spectrally encoded flow cytometry using few-mode fiber collection
Authors: Friedman Reut , Yelin Dvir
Published: December 2024

In fiber-based confocal microscopy, using two separate fibers for illumination and collection enables the use of a few-mode fiber to achieve an effect similar to opening the pinhole in a conventional confocal microscope. In some Fourier-domain applications, however, or when a spectral measurement is involved, the coherent light detection would lead to noticeable spectral modulation artifacts that result from differential mode delay, an effect caused by the multimode propagation in the collection fiber. After eliminating these artifacts by using mode-dependent polarization control, we demonstrate effective spectrally encoded imaging with improved signal efficiency and lower speckle noise, and only a minor, negligible reduction in lateral and axial resolutions.
A high-resolution two-step evolution experiment in yeast reveals a shift from pleiotropic to modular adaptation
Authors: Kinsler Grant , Li Yuping , Sherlock Gavin , Petrov Dmitri A.
Published: December 2024

Evolution by natural selection is expected to be a slow and gradual process. In particular, the mutations that drive evolution are predicted to be small and modular, incrementally improving a small number of traits. However, adaptive mutations identified early in microbial evolution experiments, cancer, and other systems often provide substantial fitness gains and pleiotropically improve multiple traits at once. We asked whether such pleiotropically adaptive mutations are common throughout adaptation or are instead a rare feature of early steps in evolution that tend to target key signaling pathways. To do so, we conducted barcoded second-step evolution experiments initiated from 5 first-step mutations identified from a prior yeast evolution experiment. We then isolated hundreds of second-step mutations from these evolution experiments, measured their fitness and performance in several growth phases, and conducted whole genome sequencing of the second-step clones. Here, we found that while the vast majority of mutants isolated from the first-step of evolution in this condition show patterns of pleiotropic adaptation—improving both performance in fermentation and respiration growth phases—second-step mutations show a shift towards modular adaptation, mostly improving respiration performance and only rarely improving fermentation performance. We also identified a shift in the molecular basis of adaptation from genes in cellular signaling pathways towards genes involved in respiration and mitochondrial function. Our results suggest that the genes in cellular signaling pathways may be more likely to provide large, adaptively pleiotropic benefits to the organism due to their ability to coherently affect many phenotypes at once. As such, these genes may serve as the source of pleiotropic adaptation in the early stages of evolution, and once these become exhausted, organisms then adapt more gradually, acquiring smaller, more modular mutations.
Whole brain functional connectivity: Insights from next generation neural mass modelling incorporating electrical synapses
Authors: Forrester Michael , Petros Sammy , Cattell Oliver , Lai Yi Ming , O’Dea Reuben D. , Sotiropoulos Stamatios , Coombes Stephen
Published: December 2024

The ready availability of brain connectome data has both inspired and facilitated the modelling of whole brain activity using networks of phenomenological neural mass models that can incorporate both interaction strength and tract length between brain regions. Recently, a new class of neural mass model has been developed from an exact mean field reduction of a network of spiking cortical cell models with a biophysically realistic model of the chemical synapse. Moreover, this new population dynamics model can naturally incorporate electrical synapses. Here we demonstrate the ability of this new modelling framework, when combined with data from the Human Connectome Project, to generate patterns of functional connectivity (FC) of the type observed in both magnetoencephalography and functional magnetic resonance neuroimaging. Some limited explanatory power is obtained via an eigenmode description of frequency-specific FC patterns, obtained via a linear stability analysis of the network steady state in the neigbourhood of a Hopf bifurcation. However, direct numerical simulations show that empirical data is more faithfully recapitulated in the nonlinear regime, and exposes a key role of gap junction coupling strength in generating empirically-observed neural activity, and associated FC patterns and their evolution. Thereby, we emphasise the importance of maintaining known links with biological reality when developing multi-scale models of brain dynamics. As a tool for the study of dynamic whole brain models of the type presented here we further provide a suite of C++ codes for the efficient, and user friendly, simulation of neural mass networks with multiple delayed interactions.