bluuebunny/crossref_metadata_2025 huggingface dataset:
Microscopic anatomy of the oesophagus in the southern white‐breasted hedgehog (Erinaceus concolor) a histochemical, stereological, and scanning electron microscope study
Authors: Massoud Diaa , Abumandour Mohamed , Hamdi Hamida , Morsy Kareem , El‐kott Attalla F. , Attaallah Amany , Shalaby Fatma Mohsen
Published: November 2022

The present work was designed to investigate the microscopic structure of the oesophagus in the southern white‐breasted hedgehog (Erinaceus concolor) using histochemical staining, Scanning electron microscope (SEM), and stereological procedures. Four adult males were included in our study. Serial sections of the entire length of the oesophagus were stained with aldehyde fuchsin, alcian blue (pH 2.5), Periodic acid Schiff (PAS), and Masson's trichrome. Then, the total volume of the oesophagus, and the total volume of its different layers, were estimated using Cavalieri's principle. The oesophageal epithelium was a non‐keratinized stratified squamous type. Muscularis mucosa was present as a thick layer between lamina propria and submucosa and its thickness was increased toward the stomach. Tunica submucosa was a loose connective tissue containing an oesophageal gland with PAS‐positive and AB‐positive reactions throughout the submucosa and become denser toward the stomach. The tunica muscularis consisted of two distinct striated muscle layers, and its thickness was decreased toward the stomach. On SEM images, the cervical and thoracic oesophagus showed shallow folding, while the abdominal part had deeper folds. The present findings indicate that the histological properties of the oesophagus in southern white‐breasted hedgehogs have slight similarities with rodents and considering its epithelium, submucosal glands and tunica muscularis more resemble with dog oesophagus. The obtained results may be quite helpful to improve the current knowledge of the histophysiology of the hedgehog gastrointestinal tract as a member of eulipotyplan mammals and as a pet for biologists and veterinarians.
Reporting and risk of bias of prediction models based on machine learning methods in preterm birth: A systematic review
Authors: Yang Qiuyu , Fan Xia , Cao Xiao , Hao Weijie , Lu Jiale , Wei Jia , Tian Jinhui , Yin Min , Ge Long
Published: November 2022

Introduction

There was limited evidence on the quality of reporting and methodological quality of prediction models using machine learning methods in preterm birth. This systematic review aimed to assess the reporting quality and risk of bias of a machine learning‐based prediction model in preterm birth.

Material and methods

We conducted a systematic review, searching the PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disk, VIP Database, and WanFang Data from inception to September 27, 2021. Studies that developed (validated) a prediction model using machine learning methods in preterm birth were included. We used the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement and Prediction model Risk of Bias Assessment Tool (PROBAST) to evaluate the reporting quality and the risk of bias of included studies, respectively. Findings were summarized using descriptive statistics and visual plots. The protocol was registered in PROSPERO (no. CRD 42022301623).

Results

Twenty‐nine studies met the inclusion criteria, with 24 development‐only studies and 5 development‐with‐validation studies. Overall, TRIPOD adherence per study ranged from 17% to 79%, with a median adherence of 49%. The reporting of title, abstract, blinding of predictors, sample size justification, explanation of model, and model performance were mostly poor, with TRIPOD adherence ranging from 4% to 17%. For all included studies, 79% had a high overall risk of bias, and 21% had an unclear overall risk of bias. The analysis domain was most commonly rated as high risk of bias in included studies, mainly as a result of small effective sample size, selection of predictors based on univariable analysis, and lack of calibration evaluation.

Conclusions

Reporting and methodological quality of machine learning‐based prediction models in preterm birth were poor. It is urgent to improve the design, conduct, and reporting of such studies to boost the application of machine learning‐based prediction models in preterm birth in clinical practice.
Nudging to handwash during the pandemic – The use of visual priming and salience
Authors: Prasetyo Dimas Budi , Sofyan Lury , Muchtar Pyan Amin , Dewi Dwiana Fajriati
Published: November 2022

The government has been asserting efforts to control the pandemic's infection rate by influencing people to comply with the health protocols. While these efforts aim to change people's behavior, behavior approaches like nudge are under‐utilized, which thus motivates this paper. Nudge is the form of persuasion where a simple and subtle trigger is applied to encourage expected behavior. We conducted two studies to identify the right visual cues that best increase handwashing behavior. In Study 1 (online), we created some posters with varying concepts and held an online survey with 1,648 participants. Exploiting a pre‐post design, we found that visual handwashing with foam and rhyming messages in the poster can lead to higher handwashing intention. In Study 2 (offline), we introduced four treatment types and observed the handwashing behavior of government officials and visitors using a hidden camera. With a total of 2062 people observed during the experiment, we found that while the treatment of procuring a proper facility did not yield a significant change in handwashing rate, our nudge treatment with the salient poster and salient footprints towards the sink increased the handwashing rate.
Guillain‐Barré syndrome after COVID‐19 vaccines: A Tunisian case series
Authors: Berrim Khouloud , Lakhoua Ghozlane , Zaiem Ahmed , Charfi Ons , Aouinti Imen , Kastalli Sarrah , Daghfous Riadh , El Aidli Sihem
Published: November 2022

As the COVID‐19 vaccination campaign progresses worldwide, Guillain–Barré syndrome (GBS) vaccine‐related cases have been reported. We carried out a retrospective, descriptive study of GBS patients following COVID‐19 vaccine, submitted to the National Pharmacovigilance Center of Tunis during the period between March 2021 and May 2022. Our study aimed to identify epidemiological and clinical features of COVID‐19 vaccine‐associated GBS. We found 9 cases of GBS post COVID‐19 vaccination; 5 of them were excluded due to the lack of information, whereas 4 cases were included in this study. Men represented 75% (3/4) of the cases. The most frequently reported vaccine type was ChAdOx1 nCoV‐19 vaccine (n = 2 reports [50%]), Ad26.COV2.S vaccine and BNT162b2 vaccine in 1. The mean time interval from vaccination to symptom onset was 15.3 days. Clinical manifestations were different: classical GBS in two cases and GBS with unilateral facial palsy in the other 2 cases. All patients were treated with a course of intravenous immunoglobulin for 5 days. Three patients reported clinical improvement while one case (25%) showed treatment‐related fluctuations. Our observations suggest that COVID‐19 vaccines may be associated with GBS. Continuous surveillance and further studies are warranted to assess the significance of the association.
The development of number line accuracy in elementary school children: A cross‐country longitudinal study
Authors: Tikhomirova Tatiana , Malykh Artem , Lysenkova Irina , Kuzmina Yulia , Malykh Sergey
Published: November 2022

Background

Number line accuracy (NL accuracy) shows improvement over the course of a school education. However, there are practically no cross‐country longitudinal studies of NL accuracy over the whole course of elementary school.

Aims

This study investigated the developmental trajectories of NL accuracy and its types across the elementary school years in two countries—Russia and Kyrgyzstan.

Sample(s)

The analyses were carried out on the data collected from the sample of 508 schoolchildren at Grades 1, 2, 3 and 4 (aged 6.4–11.9 years) from Russia and Kyrgyzstan, who were surveyed as part of the ‘Cross‐cultural Longitudinal Analysis of Student Success’ project.

Methods

The participants were administered the ‘Number Line’ computerized test task and a paper‐and‐pencil ‘Standard Progressive Matrices’ test at the end of each academic year.

Results

During the course of the elementary school education, NL accuracy increases nonlinearly in both samples from Grade 1 to Grade 4, with a pronounced increase in the rate of improvement from the first to the second year. Cross‐country differences in NL accuracy were observed during each year of schooling as well as in the growth of NL accuracy. The development of NL accuracy is described by a model with two developmental types: (1) ‘high start and growth’ (93% of the pooled sample) and (2) ‘low start and no growth’ (7%).

Conclusions

Both NL accuracy and the rate of its growth during elementary school depend on educational conditions. Cross‐country differences in the distribution of schoolchildren by these two developmental types were statistically insignificant.
Probiotics enhances anti‐tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer
Authors: Miyake Makito , Oda Yuki , Owari Takuya , Iida Kota , Ohnishi Sayuri , Fujii Tomomi , Nishimura Nobutaka , Miyamoto Tatsuki , Shimizu Takuto , Ohnishi Kenta , Hori Shunta , Morizawa Yosuke , Gotoh Daisuke , Nakai Yasushi , Torimoto Kazumasa , Tanaka Nobumichi , Fujimoto Kiyohide
Published: November 2022

Chemotherapy drugs, such as gemcitabine and cisplatin (GC), are frequently administered to patients with advanced urothelial carcinoma, however the influence of the gut microbiota on their action is unclear. Thus, we investigated the effects of GC on the gut microbiome and determined whether oral supplementation with a probiotics mixture of Lactobacillus casei Shirota and Bifidobacterium breve enhanced the anti‐tumor immune response. After subcutaneous inoculation with MBT2 murine bladder cancer cells, syngenic C3H mice were randomly allocated into eight groups. The gut microbiome cluster pattern was altered in both the GC and oral probiotics groups (p = 0.025). Both tumor‐bearing conditions (no treatment) and GC chemotherapy influenced Pseudoclostridium, Robinsoniella, Merdimonas, and Phocea in the gut. Furthermore, comparison of the GC‐treated and GC + probiotics groups revealed an association of four methyltransferase family enzymes and two short‐change fatty acid‐related enzymes with oral probiotics use. A significant difference in tumor volume was observed between the GC and GC + probiotics groups at week 2 of treatment. Additionally, decreased recruitment of cancer‐associated fibroblasts and regulatory T cells, and activation of CD8+ T cells and dendritic cells were observed in the tumor microenvironment. Our findings reveal the positive effects of a probiotics mixture of Lactobacillus and Bifidobacterium in enhancing anti‐tumor effects through the gut–tumor immune response axis. Future clinical trials are needed to evaluate the full benefits of this novel supplement with oral probiotics in patients with advanced urothelial carcinoma.
MEK1‐dependent MondoA phosphorylation regulates glucose uptake in response to ketone bodies in colorectal cancer cells
Authors: Zhu Yemin , Xu Nannan , Wu Siming , Luan Yu , Ke Huiyi , Wu Lifang , Li Yakui , Lu Ying , Xing Xindan , Tian Na , Liu Qi , Tong Lingfeng , Hu Lei , Ji Yingning , Chen Zhangbing , Zhang Ping , Tong Xuemei
Published: November 2022

The Mondo family transcription factor MondoA plays a pivotal role in sensing metabolites, such as glucose, glutamine, and lactic acid, to regulate glucose metabolism and cell proliferation. Ketone bodies are important signals for reducing glucose uptake. However, it is unclear whether MondoA functions in ketone body‐regulated glucose transport. Here we reported that ketone bodies promoted MondoA nuclear translocation and binding to the promoter of its target gene TXNIP. Ketone bodies reduced glucose uptake, increased apoptosis and decreased proliferation of colorectal cancer cells, which was impeded by MondoA knockdown. Moreover, we identified MEK1 as a novel component of the MondoA protein complex using a proteomic approach. Mechanistically, MEK1 interacted with MondoA and enhanced tyrosine 222, but not serine or threonine, phosphorylation of MondoA, inhibiting MondoA nuclear translocation and transcriptional activity. Ketone bodies decreased MEK1‐dependent MondoA phosphorylation by blocking MondoA and MEK1 interaction, leading to MondoA nuclear translocation, TXNIP transcription, and inhibition of glucose uptake. Therefore, our study not only demonstrated that ketone bodies reduce glucose uptake, promote apoptosis, and inhibit cell proliferation in colorectal cancer cells by regulating MondoA phosphorylation but also identified MEK1‐dependent phosphorylation as a new mechanism to manipulate MondoA activity.
Evaluation of a multidisciplinary, multimodal pain management protocol following pancreas transplantation
Authors: Lindner Brian K. , Lakhani Shahzia A. , Cooper Matthew , Nguyen Brian M. , Vranic Gayle , Yi Soo Y. , Abrams Peter
Published: November 2022

Introduction

Patients undergoing solid‐organ transplantation demonstrate pain arising from both the surgical intervention and pre‐existing comorbidities. High levels of opioid use both pre‐ and post‐transplant are associated with unfavorable transplant outcomes. Patient education, multimodal therapy, and discharge planning have all been demonstrated to reduce opioid use after transplant.

Methods

This is a single‐center, retrospective study analyzing patients before and after implementation of a multimodal, multidisciplinary pain management protocol. Morphine milligram equivalents (MMEs) use during the index transplant hospitalization and the need for opioids at discharge was compared between the pre‐ and post‐protocol groups.

Results

A total of 52 patients were included in the study, 31 in the pre and 21 in the post‐protocol groups. Inpatient MME use was reduced from 135.5 to 67.5 MMEs after protocol implementation. Additionally, the number of patients discharged on opioids following transplant decreased from 90.3% to 47.6%. Pain scores, length of stay (LOS), and return of bowel function was not different between groups.

Conclusion

The implementation of a multimodal, multidisciplinary pain management protocol significantly decreased opioid use during the post‐surgical hospitalization and in the 6 months following transplantation. A combination of non‐opioid analgesics, patient education, and discharge planning can be beneficial elements in pancreas transplant pain management.
Intuitive cooperators: Time pressure increases children's cooperative decisions in a modified public goods game
Authors: Corbit John , Dockrill Mya , Hartlin Stef , Moore Chris
Published: November 2022

There is mounting empirical evidence to suggest that adults are intuitively cooperative. When presented with a cooperative dilemma between self‐maximizing and benefitting the common good, decisions made quickly are more likely to be cooperative, whereas slow decisions tend to favor self‐interest. To investigate the ontogenetic origins of intuitive cooperation, we examined the development of intuitive cooperation in middle childhood. We presented 150 children (7–12 years of age) with an online child‐friendly public goods game where participants had a choice between giving two resources to themselves or four to their group. Participants were assigned to one of three decision time conditions; speeded, neutral, or delayed. We found that when decisions were speeded, children were more likely to cooperate compared to when decisions were unconstrained or delayed. Furthermore, children's intuitive choices only favored cooperation if they believed their peers were also cooperative. This pattern of findings held across the age range included in this study. Our findings suggest that in middle and late childhood, children are intuitively cooperative when making decisions to benefit the common good.

Highlights

Time pressure increases children's cooperation in a public goods game, compared to when decisions are delayed or unconstrained.

Between 7 and 12 years of age children engage in costly cooperation most of the time regardless of decision time.

When children believe others are generally cooperative, their intuition is to cooperate.

From middle to late childhood, intuitive decisions favor costly cooperation towards the common good.
Transition from paediatric to adult care in young people with diabetes; A structured programme from a regional diabetes service, Auckland, New Zealand
Authors: Hornung Rosalie J. , Reed Peter W. , Gunn Alistair J. , Albert Ben , Hofman Paul L. , Farrant Bridget , Jefferies Craig
Published: November 2022

Aim

To assess participation with a structured transition programme for adolescents with diabetes.

Methods

Data from a regional cohort aged less than 16 years of age with type 1 (T1) and type 2 diabetes (T2D) in Auckland, New Zealand (2006–2016). Participation was defined as opting into a structured transition programme.

Results

Five hundrend and twelve adolescents who were to be transferred to adult care (476 type 1 (T1D) and 36 type 2 (T2D)), overall participation rate of 83%, 86% (408/476) with T1D compared to 47% (17/36) with T2D. Within the cohort of T1D, participation rates for Māori and Pacific were lower (74% and 77%, respectively) than New Zealand Europeans (88%, p = 0.020 and p = 0.039, respectively). Lower socio‐economic status was associated with reduced participation (77%) compared to higher socio‐economic status (90%, p = 0.002).

Of the 476 T1D who participated, 408 (96%) subsequently attended at least one adult service clinic (“capture”). 42% attended an adult clinic within the planned 3 months, 87% at 6 months and retention in adult clinics over 5 years of follow‐up was 78%. By contrast, the 68 young people with T1D who did not participate in the structured transition had a capture rate of 78% (p < 0.001) and retention of 63% (p = 0.036).

Conclusions

In adolescents with diabetes, a formal transition from a paediatric service was associated with high rates of adult capture and subsequent retention in adult care over a 5‐year follow‐up period. Low socio‐economic status, Māori or Pacific ethnicity and T2D were associated with reduced participation in the structured transition programme.
Machine learning for the early prediction of infants with electrographic seizures in neonatal hypoxic‐ischemic encephalopathy
Authors: Pavel Andreea M. , O'Toole John M. , Proietti Jacopo , Livingstone Vicki , Mitra Subhabrata , Marnane William P. , Finder Mikael , Dempsey Eugene M. , Murray Deirdre M. , Boylan Geraldine B. ,   ANSeR Consortium
Published: November 2022

Objective

To assess if early clinical and electroencephalography (EEG) features predict later seizure development in infants with hypoxic‐ischemic encephalopathy (HIE).

Methods

Clinical and EEG parameters <12 h of birth from infants with HIE across eight European Neonatal Units were used to develop seizure‐prediction models. Clinical parameters included intrapartum complications, fetal distress, gestational age, delivery mode, gender, birth weight, Apgar scores, assisted ventilation, cord pH, and blood gases. The earliest EEG hour provided a qualitative analysis (discontinuity, amplitude, asymmetry/asynchrony, sleep–wake cycle [SWC]) and a quantitative analysis (power, discontinuity, spectral distribution, inter‐hemispheric connectivity) from full montage and two‐channel amplitude‐integrated EEG (aEEG). Subgroup analysis, only including infants without anti‐seizure medication (ASM) prior to EEG was also performed. Machine‐learning (ML) models (random forest and gradient boosting algorithms) were developed to predict infants who would later develop seizures and assessed using Matthews correlation coefficient (MCC) and area under the receiver‐operating characteristic curve (AUC).

Results

The study included 162 infants with HIE (53 had seizures). Low Apgar, need for ventilation, high lactate, low base excess, absent SWC, low EEG power, and increased EEG discontinuity were associated with seizures. The following predictive models were developed: clinical (MCC 0.368, AUC 0.681), qualitative EEG (MCC 0.467, AUC 0.729), quantitative EEG (MCC 0.473, AUC 0.730), clinical and qualitative EEG (MCC 0.470, AUC 0.721), and clinical and quantitative EEG (MCC 0.513, AUC 0.746). The clinical and qualitative‐EEG model significantly outperformed the clinical model alone (MCC 0.470 vs 0.368, p‐value .037). The clinical and quantitative‐EEG model significantly outperformed the clinical model (MCC 0.513 vs 0.368, p‐value .012). The clinical and quantitative‐EEG model for infants without ASM (n = 131) had MCC 0.588, AUC 0.832. Performance for quantitative aEEG (n = 159) was MCC 0.381, AUC 0.696 and clinical and quantitative aEEG was MCC 0.384, AUC 0.720.

Significance

Early EEG background analysis combined with readily available clinical data helped predict infants who were at highest risk of seizures, hours before they occur. Automated quantitative‐EEG analysis was as good as expert analysis for predicting seizures, supporting the use of automated assessment tools for early evaluation of HIE.
Principles of EU criminalisation and their varied normative strength: Harm and effectiveness
Authors: Peršak Nina
Published: November 2022

The increasing legislative activity of the Union in the field of criminal law highlights the need for a normative justification of EU action in this area. The article first examines and compares the existing EU legislative grounds for criminalisation, coupled with EU criminal policy orientations, with the well‐established criminalisation grounds recognised in criminalisation theory in order to distil what the underlying substantive criminalisation principles behind EU criminal law may be. This article then scrutinises ‘effectiveness’ as the potential normative principle of EU criminalisation. It is submitted that, within EU criminal law and policy, effectiveness has become a sort of ‘hybrid criminalisation principle’, joining pragmatic with seemingly normative criminalisation‐legitimising considerations. However, the article argues that effectiveness should remain primarily conceptualised as a pragmatic criminalisation consideration, not as a normative substantive criminalisation principle that acts as the first and most important criminalisation criterion determining the content of what may be criminalised.
Political colonization of a regulatory organization in a developing country: Implications for public accountability and organizational reform
Authors: Masum Mahmud Al , Parker Lee D. , Yapa Prem W. Senarath
Published: November 2022

The aim of this paper is to investigate how politically based trade union power can determine the fate of a regulatory body's organizational reform and undermine public accountability in a purportedly democratic developing country (DC). A large regulatory organization in Bangladesh was examined as a case study to uncover how political actors and power were embedded in a World Bank (WB)‐led organizational reform designed to contribute to public accountability and democracy. Interviews and media (newspaper) were utilized to identify the contestation of powers at macro‐ and micro‐levels. The explanation of reform implementation was informed by New Institutional Theory and its derived concept of institutional logics. Finding that political recruitment of the organization's senior executives made it susceptible to the pressures of political agents, the study reveals how politically supported union actions interrupted a WB‐led organizational reform that was seeking to secure democracy and public accountability. It finds that the pre‐existing institutional arrangements resurfaced over time as the political agents secured more power to restore past practices that adversely impacted public accountability. The lack (absence) of accountability in a so‐called democratic regime facilitated political interference with the regulatory governance and reforms that undermined organizational accountability to external stakeholders. The case‐study organization's institutional environment, agents, and interests were unique situational conditioners that nonetheless may be relevant to other similar public accountability organizations in DCs. The findings of the paper have important implications for policymakers who design, implement, and evaluate public accountability reforms in DCs.
Stakeholder outcome prioritization in the Biologic Abatement and Capturing Kids' Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK‐OFF JSpA) trial
Authors: Neu Emily , Sears Cora , Brandon Timothy , Kohlheim Melanie , Leal Jenny , Archie Kweli , Holland English , Holland Miles , Hameed Aamena , Khan Asad , Murphy Lynn , Murphy Sean , Neu Antoinette , Neu Jerome , Neu Justin , Richmond Rachel , Suplee Dylan , Suplee Theresa , Forrest Christopher B. , Weiss Pamela F.
Published: November 2022

Background

The Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK‐OFF JSpA) study is a randomized, pragmatic trial investigating different tumour necrosis factor inhibitor de‐escalation strategies for children with sustained inactive disease. In this project, we elicited concept rankings that aided in the selection of the patient‐reported outcome (PRO) measures that should be examined as part of the BACK‐OFF JSpA trial.

Methods

We conducted a discrete choice experiment to evaluate individuals' preferences regarding PROs. Stakeholders assessed a discrete list of 21 outcome concepts, each of which had a Patient‐Reported Outcome Measurement Information System (PROMIS) measure associated with it. PROMIS measures are self‐ or proxy‐reported instruments that are universally applicable to the general population and all chronic conditions. Stakeholders were required to make choices instead of expressing the strength of a preference.

Results

Fourteen caregivers, 12 patients (9–22 years old), 16 rheumatologists and three executives from health insurance companies completed the exercise, which took approximately 10 min. The discrete choice experiment resulted in an estimate of the relative importance of each outcome and rank. All stakeholder groups agreed that the primary PRO should be ‘Pain Interference’, a measure that evaluates the effect of pain on a child's everyday activities, including its impact on social, emotional, mental and physical functioning. Patients and caregivers were mostly aligned in their top priorities, with patients valuing physical health (50% of the top 10) whereas caregivers were more interested in mental health (60% of the top 10). Rheumatologists and health insurance executives were most interested in physical health outcomes, which were ranked 80% and 60% of their top 10 PROs, respectively. Overall, the patients had the most diverse set of prioritized outcomes, including at least one of each category in their top 10 rank order of importance. Patients were also the only stakeholders to prioritize ‘social’ health.

Conclusions

Patients and caregivers were mostly aligned in their outcome priority rankings. The rank‐order list directly informed the creation of a profile of PRO measures for our upcoming trial.

Patient or Public Contribution

Stakeholder partners helped with acquisition of data and lead parent partners helped interpret data.
Vascular endothelial growth factor‐C in activating vascular endothelial growth factor receptor‐3 and chemokine receptor‐4 in melanoma adhesion
Authors: Hlophe Yvette N. , Joubert Anna M.
Published: November 2022

Vascular endothelial growth factor‐C (VEGF‐C) binds to receptor vascular endothelial growth factor receptor‐3 (VEGFR‐3) expressed on lymphatic endothelial and melanoma cells. Binding of VEGF‐C to VEGFR‐3 enhances receptor phosphorylation that activates mitogen‐activated protein kinase (MAP‐K) and phosphatidylinositol‐3‐kinase (PI3K). These signalling pathways regulate cell migration and adhesion in response to internal or external changes.

In addition, the overexpression of VEGF‐C upregulates chemokine receptor CXCR‐4 in tumours (melanoma). CXCR‐4 is expressed on cells of the immune system (natural killer cells) and facilitates the migration of leukocytes in response to the CXCL12 ligand. The latter is expressed by lymphatic endothelial cells and by stromal cells in the tumour microenvironment (TME). The gradient established between CXCR‐4 expressed on tumour cells and CXCL12 produced by stromal and lymphatic endothelial cells enhances tumour cell metastasis.

3‐(4‐Dimethylamino‐naphthalen‐1‐ylmethylene)‐1, 3‐dihydroindol‐2‐one, MAZ‐51, is an indolinone‐based synthetic molecule that inhibits the phosphorylation of the tyrosine kinase receptor VEGFR‐3. CTCE‐9908, a CXCR‐4 antagonist derived from human CXCL12, hinders receptor phosphorylation and the subsequent signalling pathways that would be activated.

VEGF‐C is stimulated by transforming growth factor‐beta 1 (TGF‐β1), which facilitates cell–cell and cell‐matrix adhesion by regulating cadherins through the activation of focal adhesion kinase (FAK) and mediates paxillin upregulation.

Increased VEGF‐C protein levels stimulated by TGF‐β bound to VEGFR‐3 impact on intracellular pathways that promote tumour cell adhesion. In addition, increased VEGF‐C protein levels lead to enhanced CXCR‐4 protein expression. Therefore, effective blocking of VEGR‐3 and CXCR‐4 may inhibit tumour cell metastasis by hampering intracellular proteins promoting adhesion.
Endoscopic submucosal dissection for anastomotic lesions after colorectal surgery
Authors: Wang Li , Liu Zu‐Qiang , Liu Jing‐Zheng , Ma Li‐Yun , Li Xiao‐Qing , Yao Lu , Li Quan‐Lin , Zhou Ping‐Hong
Published: November 2022

Background

Endoscopic submucosal dissection (ESD) for anastomotic lesions is technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and effectiveness of ESD for anastomotic lesions of the lower gastrointestinal tract.

Method

We retrospectively investigated 55 patients with anastomotic lesions of the lower gastrointestinal tract who underwent ESD from February 2008 to January 2021. The lesions involving one or both sides of anastomoses were classified into the unilaterally involving anastomosis (UIA) or straddling anastomosis (SA) group, respectively. We collected clinicopathological characteristics, procedure‐related parameters and outcomes, and follow‐up data and analyzed the impact of anastomotic involvement.

Results

The mean age was 62.5 years, and the median procedure duration was 30 min. The rates of en bloc resection and R0 resection were 90.9% and 85.5%, respectively. Four patients (7.3%) experienced major adverse events (AEs). During a median follow‐up of 66 months (range 14–169), seven patients had local recurrence, and six patients had metastases. The 5‐year disease‐free survival and overall survival rates were 82.4% and 90.7%, respectively. The 5‐year disease ‐specific survival (DSS) rate was 93.3%. Compared with the UIA group, the SA group had significantly longer procedure duration, larger specimen, lower rates of en bloc resection and R0 resection, and shorter disease‐free survival (all P < 0.05). However, rates of AEs did not differ significantly between the two groups.

Conclusions

The short‐term and long‐term outcomes of ESD for colorectal anastomotic lesions were favorable. Although with technically challenging, ESD could be performed safely and effectively for lesions at the anastomoses.
Methods to expose subsurface objects of interest identified from 3D imaging: The intermediate sample preparation stage in the correlative microscopy workflow
Authors: Mitchell R. L. , Dunlop T. , Volkenandt T. , Russell J. , Davies P. , Spooner S. , Pleydell‐Pearce C. , Johnston R.
Published: November 2022

The correlative imaging workflow is a method of combining information and data across modes (e.g. SEM, X‐ray CT, FIB‐SEM), scales (cm to nm) and dimensions (2D–3D–4D), providing a more holistic interpretation of the research question. Often, subsurface objects of interest (e.g. inclusions, pores, cracks, defects in multilayered samples) are identified from initial exploratory nondestructive 3D tomographic imaging (e.g. X‐ray CT, XRM), and those objects need to be studied using additional techniques to obtain, for example, 2D chemical or crystallographic data. Consequently, an intermediate sample preparation step needs to be completed, where a targeted amount of sample surface material is removed, exposing and revealing the object of interest. At present, there is not one singular technique for removing varied thicknesses at high resolution and on a range of scales from cm to nm. Here, we review the manual and automated options currently available for targeted sample material removal, with a focus on those methods which are readily accessible in most laboratories. We summarise the approaches for manual grinding and polishing, automated grinding and polishing, microtome/ultramicrotome, and broad‐beam ion milling (BBIM), with further review of other more specialist techniques including serial block face electron microscopy (SBF‐SEM), and ion milling and laser approaches such as FIB‐SEM, Xe plasma FIB‐SEM, and femtosecond laser/LaserFIB. We also address factors which may influence the decision on a particular technique, including the composition, shape and size of the samples, sample mounting limitations, the amount of surface material to be removed, the accuracy and/or resolution of peripheral parts, the accuracy and/or resolution of the technique/instrumentation, and other more general factors such as accessibility to instrumentation, costs, and the time taken for experimentation. It is hoped that this study will provide researchers with a range of options for removal of specific amounts of sample surface material to reach subsurface objects of interest in both correlative and non‐correlative workflows.
Deep empirical risk minimization in finance: Looking into the future
Authors: Reppen Anders Max , Soner Halil Mete
Published: November 2022

Many modern computational approaches to classical problems in quantitative finance are formulated as empirical loss minimization (ERM), allowing direct applications of classical results from statistical machine learning. These methods, designed to directly construct the optimal feedback representation of hedging or investment decisions, are analyzed in this framework demonstrating their effectiveness as well as their susceptibility to generalization error. Use of classical techniques shows that over‐training renders trained investment decisions to become anticipative, and proves overlearning for large hypothesis spaces. On the other hand, nonasymptotic estimates based on Rademacher complexity show the convergence for sufficiently large training sets. These results emphasize the importance of synthetic data generation and the appropriate calibration of complex models to market data. A numerically studied stylized example illustrates these possibilities, including the importance of problem dimension in the degree of overlearning, and the effectiveness of this approach.
Clinical Application of the Roussouly Classification in the Sagittal Balance Reconstruction of 101 Adolescent Idiopathic Scoliosis Patients
Authors: Li Junyu , Zhang Yueyang , Zhang Yiqiao , Li Xinyi , Yang Zexi , Hu Panpan , Li Weishi , Zeng Yan , Wang Yongqiang , Sun Zhuoran , Zhou Siyu , Yu Miao
Published: November 2022

Purpose

Although Roussouly classification has been widely used in spinal surgery, it was mainly applied to degenerative scoliosis patients and correlational studies concerning adolescent idiopathic scoliosis (AIS) are still insufficient. This retrospective study explored the clinical application of Roussouly classification in surgeries and prognosis prediction for AIS.

Methods

This clinical research selected 101 AIS patients who received surgeries between August 2005 and November 2019. Whole spine standing radiographs were obtained for each patient preoperatively, postoperatively, and at the last follow‐up (>24 months). All patients were classified into “theoretical types” and “current types.” Patients were further divided into mismatch or match groups based on the consistency of their current type and theoretical type. The main parameters include: proximal junctional angle (PJA), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), fixed thoracic kyphosis (TK), global TK, fixed lumbar lordosis (LL), global LL, thoracic tilt, proximal thoracic alignment (PTA), lumbar tilt, spino‐sacral angle (SSA), and spinal tilt (ST).

Results

A total of 47.5% of AIS patients were subject to a preoperative mismatch of Roussouly classification. There was a significant difference in PI‐LL between the preoperative mismatch and match groups (p = 0.008). There was a significant difference in the rate of PI‐LL deformity between the match and mismatch groups with a preoperative mismatch (p = 0.037). A significant difference in thoracic tilt was observed between the postoperative mismatch and match groups (p = 0.019). The preoperative mismatch group has a higher risk of postoperative PI‐LL malformation than match group (OR = 2.303, 95% CI: 1.026, 5.165). When mismatch occurred postoperatively, there were significant differences between groups in the rate of pelvic deformity (p = 0.002) and PI‐LL deformity (p = 0.025) at the last follow‐up. Compared with the postoperative match group, mismatch group had an increased risk of pelvic deformity (OR = 5.029, 95% CI: 1.618, 15.629) and PJK deformity (OR = 3.017, 95% CI: 1.709, 11.375) at the last follow‐up. Short Form‐36 and Scoliosis Research Society 22 score of the match group was significantly higher than that of the mismatch group at the last follow‐up.

Conclusion

The Roussouly classification mismatch before or after operation leads to increased risks of PI‐LL deformity and pelvis deformity postoperatively or at the follow‐up, which seriously worsens the clinical symptoms and prognosis of patients. Therefore, recovering to the theoretical type in Roussouly classification may effectively improve patients' prognosis.
Ethylene‐mediated regulation of coleoptile elongation in rice seedlings
Authors: Yin Cui‐Cui , Huang Yi‐Hua , Zhang Xun , Zhou Yang , Chen Shou‐Yi , Zhang Jin‐Song
Published: November 2022

Rice is an important food crop in the world and the study of its growth and plasticity has a profound influence on sustainable development. Ethylene modulates multiple agronomic traits of rice as well as abiotic and biotic stresses during its lifecycle. It has diverse roles, depending on the organs, developmental stages and environmental conditions. Compared to Arabidopsis (Arabidopsis thaliana), rice ethylene signalling pathway has its own unique features due to its special semiaquatic living environment and distinct plant structure. Ethylene signalling and responses are part of an intricate network in crosstalk with internal and external factors. This review will summarize the current progress in the mechanisms of ethylene‐regulated coleoptile growth in rice, with a special focus on ethylene signaling and interaction with other hormones. Insights into these molecular mechanisms may shed light on ethylene biology and should be beneficial for the genetic improvement of rice and other crops.
Challenges and future scope of exosomes in the treatment of cardiovascular diseases
Authors: Ranjan Prabhat , Colin Karen , Dutta Roshan Kumar , Verma Suresh Kumar
Published: November 2022

Exosomes are nanosized vesicles that carry biologically diverse molecules for intercellular communication. Researchers have been trying to engineer exosomes for therapeutic purposes by using different approaches to deliver biologically active molecules to the various target cells efficiently. Recent technological advances may allow the biodistribution and pharmacokinetics of exosomes to be modified to meet scientific needs with respect to specific diseases. However, it is essential to determine an exosome's optimal dosage and potential side effects before its clinical use. Significant breakthroughs have been made in recent decades concerning exosome labelling and imaging techniques. These tools provide in situ monitoring of exosome biodistribution and pharmacokinetics and pinpoint targetability. However, because exosomes are nanometres in size and vary significantly in contents, a deeper understanding is required to ensure accurate monitoring before they can be applied in clinical settings. Different research groups have established different approaches to elucidate the roles of exosomes and visualize their spatial properties. This review covers current and emerging strategies for in vivo and in vitro exosome imaging and tracking for potential studies.

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Role of ZnO and MgO interfaces on the growth and optoelectronic properties of atomic layer deposited Zn1−xMgxO films
Authors: Gnanasambandan Poorani , Adjeroud Noureddine , Leturcq Renaud
Published: November 2022

Zn1−xMgxO films with very precise Mg content are of strong interest for the development of buffer layers on copper-indium-gallium-sulfide solar cells. Atomic layer deposition (ALD) has been successfully used for buffer layers with appropriate electronic properties; however, a good understanding of the growth properties of the ternary oxide is still lacking. Here, we investigate the role of the ZnO/MgO interface on the growth and resulting optoelectronic properties by varying the supercycle parameters (pulse ratio and bilayer period) of the ALD process. We demonstrate that the growth of the MgO layer is enhanced by the ZnO surface, describing the interplay between ZnO and MgO interfaces on the growth of Zn1−xMgxO films. The optical properties of the film not only depend on the Mg content but also on the bilayer period at a given Mg content. More specifically, the bandgap for a given Mg composition is high for the smallest bilayer period 5, starts decreasing slightly for bilayer periods between 10 and 20 due to the increase in thickness of the ZnO layer and confinement effects, and falls to a bandgap of ZnO as the bilayer period increases further >40. With the change in Zn1−xMgxO films from well-mixed to multilayer material as the bilayer period is varied, we illustrate that the optical properties of Zn1−xMgxO can be tuned effectively without largely altering the composition. Probing the effect of the bilayer period on the ternary oxides by ALD is a useful tool in understanding the mixing and interplay of binary materials that can be applied for many other materials.
Genetic slippage after sex maintains diversity for parasite resistance in a natural host population
Authors: Ameline Camille , Voegtli Felix , Andras Jason , Dexter Eric , Engelstädter Jan , Ebert Dieter
Published: November 2022

Although parasite-mediated selection is a major driver of host evolution, its influence on genetic variation for parasite resistance is not yet well understood. We monitored resistance in a large population of the planktonic crustacean
Daphnia magna
over 8 years, as it underwent yearly epidemics of the bacterial pathogen
Pasteuria ramosa
. We observed cyclic dynamics of resistance: Resistance increased throughout the epidemics, but susceptibility was restored each spring when hosts hatched from sexual resting stages. Host resting stages collected across the year showed that largely resistant host populations can produce susceptible sexual offspring. A genetic model of resistance developed for this host-parasite system, based on multiple loci and strong epistasis, is in partial agreement with our findings. Our results reveal that, despite strong selection for resistance in a natural host population, genetic slippage after sexual reproduction can be a strong factor for the maintenance of genetic diversity of host resistance.
Diabetic hyperglycemia promotes primary tumor progression through glycation-induced tumor extracellular matrix stiffening
Authors: Wang Wenjun , Hapach Lauren A. , Griggs Lauren , Smart Kyra , Wu Yusheng , Taufalele Paul V. , Rowe Matthew M. , Young Katherine M. , Bates Madison E. , Johnson Andrew C. , Ferrell Nicholas J. , Pozzi Ambra , Reinhart-King Cynthia A.
Published: November 2022

Diabetes mellitus is a complex metabolic disorder that is associated with an increased risk of breast cancer. Despite this correlation, the interplay between tumor progression and diabetes, particularly with regard to stiffening of the extracellular matrix, is still mechanistically unclear. Here, we established a murine model where hyperglycemia was induced before breast tumor development. Using the murine model, in vitro systems, and patient samples, we show that hyperglycemia increases tumor growth, extracellular matrix stiffness, glycation, and epithelial-mesenchymal transition of tumor cells. Upon inhibition of glycation or mechanotransduction in diabetic mice, these same metrics are reduced to levels comparable with nondiabetic tumors. Together, our study describes a novel biomechanical mechanism by which diabetic hyperglycemia promotes breast tumor progression via glycating the extracellular matrix. In addition, our work provides evidence that glycation inhibition is a potential adjuvant therapy for diabetic cancer patients due to the key role of matrix stiffening in both diseases.
Pointed-end processive elongation of actin filaments by
Vibrio
effectors VopF and VopL
Authors: Kudryashova Elena , Ankita  , Ulrichs Heidi , Shekhar Shashank , Kudryashov Dmitri S.
Published: November 2022

According to the cellular actin dynamics paradigm, filaments grow at their barbed ends and depolymerize predominantly from their pointed ends to form polar structures and do productive work. We show that actin can elongate at the pointed end when assisted by
Vibrio
VopF/L toxins, which act as processive polymerases. In cells, processively moving VopF/L speckles are inhibited by factors blocking the pointed but not barbed ends. Multispectral single-molecule imaging confirmed that VopF molecules associate with the pointed end, actively promoting its elongation even in the presence of profilin. Consequently, VopF/L can break the actin cytoskeleton’s polarity by compromising actin-based cellular processes. Therefore, actin filament design allows processive growth at both ends, which suggests unforeseen possibilities for cellular actin organization, particularly in specialized cells and compartments.
Chiroptical activity of gas-phase propylene oxide predicting the handedness of interstellar circular polarization in the presolar nebula
Authors: Garcia Adrien D. , Topin Jérémie , Bocková Jana , Jones Nykola C. , Hoffmann Søren V. , Meinert Cornelia
Published: November 2022

Propylene oxide, the first chiral molecule recently detected in the interstellar medium, has once again raised the question whether biomolecular chirality might have cosmic origins. However, accurate chiroptical properties of propylene oxide in the ultraviolet spectral range necessary to suggest possible asymmetric synthetic routes in the gas phase are scarce. Here, we report on the first experimental measurements of the anisotropy spectra of gas-phase propylene oxide in the vacuum ultraviolet spectral range. Our experimental results provide novel insights into the handedness of interstellar circular polarization at the dawn of molecular evolution of our star- and planet-forming region. Besides the fundamental importance of this new investigation for understanding the origin and evolution of homochirality on Earth, our high-resolution experimental electronic circular dichroism data will inspire new efforts in quantum computational spectroscopy.