bluuebunny/crossref_metadata_2025 huggingface dataset:
Studying eruption patterns of mandibular third molars for forensic age assessment: Introducing current reference data from a population of black South Africans
Authors: Timme Maximilian , Viktorov Jan , Steffens Laurin , Streeter Adam , Karch André , Smit Chané , Robinson Liam , Bernitz Herman , Schmeling Andreas
Published: May 2024

Introduction

Evaluation of the eruption of mandibular third molars in orthopantomograms (OPGs) is a method of forensic age assessment. The objective of our study was to provide valid reference data for this trait within a population of black South Africans. The study was guided by the criteria for reference studies in age assessment.

Materials and methods

A study population from Pretoria, South Africa comprising 670 OPGs obtained from 338 black females and 332 black males aged between 15.00 and 25.97 years was analysed. All OPGs were performed for medical indication during the period from 2011 to 2022 and were retrospectively evaluated. From the 670 OPGs, a total of 1021 mandibular third molars were evaluated. The assessment of mandibular third molars was conducted using the staging scale presented by Olze et al. in 2012. Two experienced dentists evaluated the OPGs independently of each other. If the two examiners diverged in their assessments, a consensus stage was assigned.

Results

As expected, the mean, median and minimal age increased with higher stages for both teeth and both sexes. The minimum age recorded for stage D, indicating complete tooth eruption, was 15.79 years in females and 16.62 years in males.

Conclusion

As it is the case for previous reference studies in other countries, placing exclusive reliance on the evaluation of mandibular third molar eruption is inadequate for ascertaining the age of majority among Black South Africans. Future studies need to examine if our results are transferable to other countries in Sub-Saharan Africa.
JEWELFISH: 24-month results from an open-label study in non-treatment-naïve patients with SMA receiving treatment with risdiplam
Authors: Chiriboga Claudia A. , Bruno Claudio , Duong Tina , Fischer Dirk , Mercuri Eugenio , Kirschner Janbernd , Kostera-Pruszczyk Anna , Jaber Birgit , Gorni Ksenija , Kletzl Heidemarie , Carruthers Imogen , Martin Carmen , Scalco Renata S. , Fontoura Paulo , Muntoni Francesco ,   the JEWELFISH Study Group
Published: May 2024

Risdiplam is a once-daily oral, survival of motor neuron 2 (SMN2) splicing modifier approved for the treatment of spinal muscular atrophy (SMA). JEWELFISH (NCT03032172) investigated the safety, tolerability, pharmacokinetics (PK), and PK/pharmacodynamic (PD) relationship of risdiplam in non-treatment-naïve patients with SMA. JEWELFISH enrolled adult and pediatric patients (N = 174) with confirmed diagnosis of 5q-autosomal recessive SMA who had previously received treatment with nusinersen (n = 76), onasemnogene abeparvovec (n = 14), olesoxime (n = 71), or were enrolled in the MOONFISH study (NCT02240355) of the splicing modifier RG7800 (n = 13). JEWELFISH was an open-label study with all participants scheduled to receive risdiplam. The most common adverse event (AE) was pyrexia (42 patients, 24%) and the most common serious AE (SAE) was pneumonia (5 patients, 3%). The rate of AEs and SAEs decreased by > 50% from the first to the second year of treatment, and there were no treatment-related AEs that led to withdrawal from treatment. An increase in SMN protein in blood was observed following risdiplam treatment and sustained over 24 months of treatment irrespective of previous treatment. Exploratory efficacy assessments of motor function showed an overall stabilization in mean total scores as assessed by the 32-item Motor Function Measure, Hammersmith Functional Motor Scale—Expanded, and Revised Upper Limb Module. The safety profile of risdiplam in JEWELFISH was consistent with previous clinical trials of risdiplam in treatment-naïve patients. Exploratory efficacy outcomes are reported but it should be noted that the main aim of JEWELFISH was to assess safety and PK/PD, and the study was not designed for efficacy analysis.

Trial registration

The study was registered (NCT03032172) on ClinicalTrials.gov on January 24, 2017; First patient enrolled: March 3, 2017.
Assessing the quality of chest compressions with a DIY low-cost manikin (LoCoMan) versus a standard manikin: a quasi-experimental study in primary education
Authors: Peixoto-Pino Lucía , Isasi Santiago Martínez , Agra Martín Otero , Van Duijn Tina , Rico-Díaz Javier , Núñez Antonio Rodriguez , Furelos Roberto Barcala
Published: May 2024

Extending the access to cardiopulmonary resuscitation (CPR) training to a wider public is an important step in increasing survivability of out-of-hospital cardiac arrest. However, often price and maintenance of CPR manikins are barriers that prevent training at schools. This study aims to evaluate the learning of hands-only (HO) CPR by practicing with a low-cost manikin (LoCoMan) with visual qualitative feedback and to compare the results with the skills acquired by practice on a conventional manikin. A quasi-experimental study with 193 schoolchildren (10 to 12 years old) who were allocated to two groups: the LoCoMan group was taught via an integrative approach (science combined with physical education (PE)) and practiced on a handmade manikin, and a control group practiced in a traditional setting with a commercial manikin (Resusci Junior, Laerdal, Norway). All participants practiced for 1 hands-on skill session before performing a post-test on an instrumented CPR manikin. The outcomes including HO-CPR performance variables were compared between groups. The LoCoMan and control groups both achieved acceptable percentage of HO-CPR quality (57% and 71%, p = 0.004). Among 6th-graders, there were no significant differences in HO-CPR quality between LoCoMan 68% and control 71%, p = 0.66. The control group achieved better chest compression depth while the LoCoMan group showed more compressions with adequate chest recoil.

     Conclusion: Schoolchildren are able to build and use a low-cost manikin with visual feedback. The integrative learning approach used in this study may be a feasible alternative methodology for training and learning HO-CPR in schools when commercial manikins are not available.

What is Known:• Access to CPR training should be universal and independent of age, location, financial means, or access to qualified instructors.• Scientific societies promote the implementation of CPR in schools, so that teachers and schoolchildren can play a multiplier role in their environment, but the gap in CPR learning is related to cultural, economic factors or access to resources and materials.

What is New:• LoCoMan may be a useful device for teaching and learning CPR in schoolchildren from the age of 10 and upwards.• LOCOMAN shows that it is feasible and possible to build a low-cost manikin (about €5 in the European Region) and to integrate it into an integrative educational project, and outlines how this could be done. this approach can be an incentive for teachers to attempt teaching CPR, but also for education outside the formal environment.
Updated dendrochronology and axial variation of climatic sensitivity in Sequoiadendron giganteum
Authors: Carroll Allyson L. , Sillett Stephen C.
Published: May 2024

Key message

Dendroclimatic sensitivity varies by axial position for Sequoiadendron giganteum: negative correlations with June temperature strengthen with height, while positive correlations with snow water are strongest in the lower trunk.

Increment cores collected along trunks of mature Sequoiadendron giganteum provide new and updated ring-width chronologies ideal for assessing how height above ground affects sensitivity of radial growth to climatic variation. Chronologies from 61 living trees at nine locations across the geographic distribution span 1973 yr. Analyses of subsets of 18–44 trees reveal that correlations between radial increments and climate (temperature, water availability) vary with axial position. Negative correlations with maximum and minimum June temperature intensify with height and are strongest at the highest position analyzed (60 m above ground). Sensitivity to the hydroclimate variable of April-1 snow water equivalent is stronger at lower trunk positions (10 m) compared to breast height or the upper trunk, and a similar relationship is identified for the standardized precipitation evapotranspiration index using a 12-month window ending in September. Drought-induced low-growth years computed as radial increment relative to the mean of 10 yr before and after are more weakly expressed at breast height compared to higher on the trunk (10–60 m). Analysis of regional upper (maximum core height = 87 m) versus lower trunk (above buttress) chronologies corroborate differing inter-annual correlations with climate depending on height above ground. Accounting for axial variation in dendroclimatic sensitivity can maximize the quality of environmental reconstructions using tree rings and improve biophysical understanding of Sequoiadendron, especially in the context of an increasingly arid climate.
Same-day discharge after percutaneous coronary procedures—Structured review and comprehensive meta-analysis
Authors: Brandt Mathias C. , Alber Hannes , Berger Rudolf , Binder Ronald K. , Mascherbauer Julia , Niessner Alexander , Schmid Martin , Wernly Bernhard , Frick Matthias ,   Austrian working group of interventional cardiology
Published: May 2024

Introduction

Percutaneous coronary intervention is a well-established revascularization strategy for patients with coronary artery disease. The safety and feasibility of performing these procedures on a same-day discharge basis for selected patients has been studied in a large number of mostly nonrandomized trials. An up to date literature review should focus on trials with radial access, representing the current standard for coronary procedures in Austria and other European countries.

Methods

The aim of this consensus statement is to review the most recent evidence for the safety and feasibility of performing same-day discharge procedures in selected patients. A structured literature search was performed using prespecified search criteria, focusing on trials with radial access procedures.

Results

A total of 44 clinical trials and 4 large meta-analyses were retrieved, spanning 21 years of clinical evidence from 2001 to 2022. The outcome data from a wide range of clinical settings were unanimous in showing no negative effect on early (24 h) or late (30 day) major adverse events after same-day discharge coronary procedures. Based on nine prospective trials a comprehensive meta-analysis was compiled. Using 1‑month major adverse events data the pooled odds ratio of same-day discharge versus overnight stay procedures was 0.66 (95% confidence interval, CI 0.35–01.24;p = 0.19; I20%), indicating a noninferiority in carefully selected patients.

Conclusion

Outcome data from same-day discharge coronary intervention trials with radial access confirm the robust safety profile showing no increase in the risk of major adverse events compared to overnight stay.
Same-day discharge after percutaneous coronary procedures—Consensus statement of the working group of interventional cardiology (AGIK) of the Austrian Society of Cardiology
Authors: Brandt Mathias C. , Alber Hannes , Berger Rudolf , Binder Ronald K. , Mascherbauer Julia , Niessner Alexander , Schmid Martin , Frick Matthias ,   the Austrian working group of interventional cardiology
Published: May 2024

Introduction

Percutaneous coronary intervention is a well-established revascularization strategy for patients with coronary artery disease. Recent technical advances such as radial access, third generation drug-eluting stents and highly effective antiplatelet therapy have substantially improved the safety profile of coronary procedures. Despite several practice guidelines and a clear patient preference of early hospital discharge, the percentage of coronary procedures performed in an outpatient setting in Austria remains low, mostly due to safety concerns.

Methods

The aim of this consensus statement is to provide a practical framework for the safe and effective implementation of coronary outpatient clinics in Austria. Based on a structured literature review and an in-depth analysis of available practice guidelines a consensus statement was developed and peer-reviewed within the working group of interventional cardiology (AGIK) of the Austrian Society of Cardiology.

Results

Based on the available literature same-day discharge coronary procedures show a favorable safety profile with no increase in the risk of major adverse events compared to an overnight stay. This document provides a detailed consensus in various clinical settings. The most important prerequisite for same-day discharge is, however, adequate selection of suitable patients and a structured peri-interventional and postinterventional management plan.

Conclusion

Based on the data analysis this consensus document provides detailed practice guidelines for the safe operation of daycare cathlab programs in Austria.
Hand-foot syndrome in cancer patients on capecitabine: examining prevalence, impacts, and associated risk factors at a cancer centre in Malaysia
Authors: King Teck Long , Voon Pei Jye , Yuen Kah Hay , Mohamed Noor Dzul Azri
Published: May 2024

Introduction

Hand-foot syndrome (HFS) significantly impacts quality of life in cancer patients undergoing capecitabine treatment. This study assessed capecitabine-associated HFS prevalence, its impacts on chemotherapy treatment, and identified risk factors in multiracial Malaysian patients.

Methods

We included adult cancer patients receiving capecitabine at Sarawak General Hospital for at least two cycles from April 1, 2021 to June 30, 2022. HFS rates, time to HFS, and proportions of HFS-related treatment modifications were determined. Characteristics between patients with and without HFS were compared and multivariable logistic regression was used to identify risk factors for all-grade HFS and grade ≥2.

Results

Among 369 patients, 185 (50.1%) developed HFS, with 14.6% experiencing grade ≥2 and 21.6% (40/185) underwent treatment modifications. Risk factors for all-grade HFS include older age (OR 1.03 95%CI 1.01, 1.06), prior chemotherapy (OR 2.09 95%CI 1.22, 3.58), higher capecitabine dose (OR 2.96 95%CI 1.62, 5.38), prolonged treatment (OR 1.36 95%CI 1.21, 1.51), folic acid intake (OR 3.27 95%CI 1.45, 7.35) and lower neutrophil count (OR 0.77 95%CI 0.66, 0.89). For HFS grade ≥2, older age (OR 1.04 95%CI 1.01, 1.08), female sex (OR 2.10 95%CI 1.05, 4.18), Chinese race (OR 2.10 95%CI 1.06, 4.18), and higher capecitabine dose (OR 2.62 95%CI 1.28, 5.35) are significant risk factors. Use of calcium channel blockers were associated with reduced risks of all-grade HFS (OR 0.27, 95%CI 0.12, 0.60) and grade ≥2 (OR 0.21 95%CI 0.06, 0.78).

Conclusion

This study provides real-world data on capecitabine-induced HFS in Malaysian patients and identifies risk factors that may offer insights into its understanding and management.
Longitudinal assessment of real-world patient adherence: a 12-month electronic patient-reported outcomes follow-up of women with early breast cancer undergoing treatment
Authors: Gebert Pimrapat , Hage Anna Maria , Blohmer Jens-Uwe , Roehle Robert , Karsten Maria Margarete
Published: May 2024

Background

Electronic patient-reported outcomes (ePROs) assess patients’ health status and quality of life, improving patient care and treatment effects, yet little is known about their use and adherence in routine patient care.

Aims

We evaluated the adherence of invasive breast cancer and ductal carcinoma in situ (DCIS) patients to ePROs follow-up and whether specific patient characteristics are related to longitudinal non-adherence.

Methods

Since November 2016, the Breast Center at Charité – Universitätsmedizin Berlin has implemented an ongoing prospective PRO routine program, requiring patients to complete ePROs assessments and consent to email-based follow-up in the first 12 months after therapy starts. Frequencies and summary statistics are presented. Multiple logistic regression models were performed to determine an association between patient characteristics and non-adherence.

Results

Out of 578 patients, 239 patients (41.3%, 95%CI: 37.3–45.5%) completed baseline assessment and all five ePROs follow-up during the first 12 months after therapy. On average, above 70% of those patients responded to the ePROs follow-up assessment. Adherence to the ePROs follow-up was higher during the COVID-19 pandemic than in the time periods before (47.4% (111/234) vs. 33.6% (71/211)). Factors associated with longitudinal non-adherence were younger age, a higher number of comorbidities, no chemotherapy, and a low physical functioning score in the EORTC QLQ-C30 at baseline.

Conclusions

The study reveals moderate adherence to 12-month ePROs follow-up assessments in invasive early breast cancer and DCIS patients, with response rates ranging from 60 to 80%. Emphasizing the benefits for young patients and those with high disease burdens might further increase adherence.
Network security AIOps for online stream data monitoring
Authors: Nguyen Giang , Dlugolinsky Stefan , Tran Viet , López García Álvaro
Published: May 2024

In cybersecurity, live production data for predictive analysis pose a significant challenge due to the inherently secure nature of the domain. Although there are publicly available, synthesized, and artificially generated datasets, authentic scenarios are rarely encountered. For anomaly-based detection, the dynamic definition of thresholds has gained importance and attention in detecting abnormalities and preventing malicious activities. Unlike conventional threshold-based methods, deep learning data modeling provides a more nuanced perspective on network monitoring. This enables security systems to continually refine and adapt to the evolving situation in streaming data online, which is also our goal. Furthermore, our work in this paper contributes significantly to AIOps research, particularly through the deployment of our intelligent module that cooperates within a monitoring system in production. Our work addresses a crucial gap in the security research landscape toward more practical and effective secure strategies.
How should cardiac xenotransplantation be initiated in Japan?
Authors: Saito Shunsuke , Miyagawa Shuji , Kawamura Takuji , Yoshioka Daisuke , Kawamura Masashi , Kawamura Ai , Misumi Yusuke , Taguchi Takura , Yamauchi Takashi , Miyagawa Shigeru
Published: May 2024

The world's first clinical cardiac xenotransplantation, using a genetically engineered pig heart with 10 gene modifications, prolonged the life of a 57-year-old man with no other life-saving options, by 60 days. It is foreseeable that xenotransplantation will be introduced in clinical practice in the United States. However, little clinical or regulatory progress has been made in the field of xenotransplantation in Japan in recent years. Japan seems to be heading toward a "device lag", and the over-importation of medical devices and technology in the medical field is becoming problematic. In this review, we discuss the concept of pig-heart xenotransplantation, including the pathobiological aspects related to immune rejection, coagulation dysregulation, and detrimental heart overgrowth, as well as genetic modification strategies in pigs to prevent or minimize these problems. Moreover, we summarize the necessity for and current status of xenotransplantation worldwide, and future prospects in Japan, with the aim of initiating xenotransplantation in Japan using genetically modified pigs without a global delay. It is imperative that this study prompts the initiation of preclinical xenotransplantation research using non-human primates and leads to clinical studies.
Social determinants of antidepressant continuation during pregnancy in the USA: findings from the ABCD cohort study
Authors: Dupuis Marc , Weir Kristie Rebecca , Vidonscky Lüthold Renata , Panchaud Alice , Baggio Stéphanie
Published: May 2024

Purpose

Patients and healthcare professionals overestimate the risks of using antidepressants during pregnancy. According to current literature, approximately half of people stop taking an anti-depressant medication when they become pregnant. Discontinuing antidepressants during pregnancy increases risks of postnatal relapses. Factors like socioeconomic status, education, and planned pregnancies play a role in the decision to continue antidepressant medication, which can worsen disparities in maternal and child health. Our aim was to identify the sociodemographic factors associated with antidepressant continuation after awareness of pregnancy.

Methods

We used representative data from the Adolescent Brain Cognitive Development (ABCD) study that captures maternal medication during pregnancy. We identified women who used antidepressants before awareness of their pregnancy. We calculated crude and adjusted associations between sociodemographic factors and continuation of antidepressant medication during pregnancy. Our model included age, education, ethnicity, first language, household income, living with a partner, having planned the pregnancy, pregnancy duration and smoking during pregnancy.

Results

In total, 199 women continued antidepressants and 100 discontinued. The logistic regressions resulted in only one significant factor: first language. Native English speakers were more likely to continue medication than other mothers (adjusted OR = 14.94, 95% CI = [2.40; 291.45], p = .015).

Conclusions

Language differences were associated with continuation of antidepressants. Non-native English speakers were more likely to discontinue antidepressants, which may lead to health inequities. This finding should be taken into account to reinforce information about the limited risks of antidepressants among people with non-English speaking backgrounds in the USA.
Resin infiltration versus fluoride varnish for visual improvement of white spot lesions during multibracket treatment. A randomized-controlled clinical trial
Authors: Kashash Yamen , Hein Sascha , Göstemeyer Gerd , Aslanalp Pervin , Weyland Manon Isabelle , Bartzela Theodosia
Published: May 2024

Aims

This study aimed to evaluate the visual improvement of resin infiltration of white spot lesions (WSL) during orthodontic treatment with the multibracket appliance (MBA) compared to fluoride varnish.

Methods

Patients aged 12–17 years with at least one WSL with an International Caries Detection and Assessment System (ICDAS) score of 1–2 during an active MBA treatment were included and randomized to receive either resin infiltration (Icon) or fluoride application (Flairesse). Standardized digital images were obtained before, one-day, one-week, one-month, three-months and six-months after treatment using a DSLR camera and a matching polarization filter. A grey reference card was used for color standardization. A Matlab routine was used to measure the color difference between adjacent healthy enamel and treated WSL. The independent-samples t-test was used for intergroup and paired-samples t-test for intragroup comparison.

Results

Images of 116 teeth from 36 patients were analyzed. The ΔE for the “Icon” treated WSL was smaller (T1ICON = 5.0 ± 1.4) than in the fluoride group (T1Fluoride = 8.4 ± 3.2). Caries infiltration significantly improved the aesthetic appearance of WSL (p < 0.001), which remained satisfactory at six months (T5ICON = 5.2 ± 1.6).

Conclusion

WSL infiltration management during orthodontic treatment was superior to topical fluoridation in not only arresting the enamel lesions but also significantly improving the aesthetic appearance of demineralized regions around the brackets.

Clinical relevance

WSL treatment in orthodontic patients is usually initiated after debonding. Research has shown that the earlier WSL is treated, the better the aesthetic outcome. There is limited data on the efficacy of resin infiltration of WSL during orthodontic treatment.
Treatment strategy for HER2-negative advanced gastric cancer: salvage-line strategy for advanced gastric cancer
Authors: Nishida Naohiro , Sakai Daisuke , Satoh Taroh
Published: May 2024

After immune checkpoint inhibitor (ICI) comes into third-line treatment of advanced gastric cancer, the therapeutic strategy has been dramatically changed. Recent first-line regimen, which consists of ICI and chemotherapeutic agents, prolonged progression-free survival, and subsequent treatment options enabled continuous treatment beyond second-line therapy. Moreover, the advent of vascular endothelial growth factor (VEGF)-targeted agents including angiogenesis inhibitors and TKIs provides an opportunity of considering the interaction between ICI and anti-VEGF agents, and facilitating novel treatment proposal. Although clinical benefit of prolonged VEGF blockade after disease progression has not been confirmed in gastric cancer, combination therapy of cytotoxic agents and anti-VEGF agent, such as irinotecan plus ramucirumab demonstrated favorable objective response rate and progression-free survival in third- or later-line setting. In this review, we discuss recent progress and future directions of later-line treatments of HER2-negative advancer gastric cancer.
Genetic differentiation of wild boar populations in a region affected by African swine fever
Authors: Simon Uta , Gerhards K , Becker S , Willems H , Friedrichs V , Forth JH , Calvelage S , Blome S , Reiner Gerald
Published: May 2024

In the European Union, African swine fever (ASF) affects wild boar (Sus scrofa) populations in several Member States. Knowledge of population connectivity is important for the implementation of control measures, in particular the establishment of effective barriers. Population genetic comparisons of neighbouring populations can be very helpful in this respect. The present study investigated the genetic differentiation of wild boar in eastern Germany. This region has been affected by ASF since September 2020. A total of 1,262 wild boars from 31 hunting grounds (populations) in ASF-affected and ASF-free districts were sampled over a total area of almost 100,000 km². The study area encompassed a network of geographical factors that promote (roads, rivers, cities) or inhibit (natural areas, habitat corridors) genetic differentiation between wild boar populations. The genetic differentiation of the areas was based on 12 microsatellite markers. Three different Bayesian algorithms were used to analyse the data. The results were combined into a common approach with 9 clusters. Based on the cluster distribution in each population, the connectivity between the areas was quantified. The strongest differentiation was found along an imaginary line along the lower Elbe valley through Berlin and the A11 freeway to the Szczecin Lagoon. In contrast, the Mecklenburg Lake District and the south-east of the study area showed strong connectivity between areas. The special features of the landscapes along the lower Elbe valley, which was assessed as highly connective, and the high barrier effect of the A11 freeway in contrast to the other freeways in the study area show that barrier effects cannot be generalised in principle, but are actually determined by the circumstances of individual structures. The results of the connectivity analysis were compared with the distribution of viral lineages and variants. The genotypes of the wild boar populations and the ASFV lineages and variants showed a good explanatory approach for the observed disease dynamics in the study area. The newly gained knowledge on barriers and regionally different connectivity between wild boar populations can support considerations and measures for the containment of ASF in the affected areas by improving the understanding of wild boar dispersal dynamics.
Incivility is systematically associated with indicators of health, stress, well-being, and the psychosocial work environment
Authors: Hasson Dan , Villaume Karin
Published: May 2024

Aim

Incivility is one of the most intrusive forms of antisocial behavior in the workplace. Using a newly constructed, single-item measure of incivility, the aim of the current study was to assess the possible prevalence of incivility in a sample from the Swedish retail industry, and to investigate possible associations between prevalence of incivility and a multitude of indicators of health, stress, well-being, and the psychosocial work environment.

Subject and methods

A total of 1014 (20%) individuals enrolled in the cross-sectional study and responded to a questionnaire, partially or fully. We conducted t-tests to assess possible differences in the indicators between those responding “Yes” versus “No” regarding prevalence of incivility at their workplace.

Results

Incivility at work was related to statistically significant differences in mean values in 32 out of 33 key indicators of health, well-being, stress, recovery, and the psychosocial work environment. Those reporting a prevalence of incivility systematically exhibited worse ratings.

Conclusion

The findings are in line with previous research. Although this study cannot infer causality, the profoundly systematic results indicate that the prevalence of workplace incivility is a bothersome problem that should be addressed. A single item about the prevalence of workplace incivility seems to be a feasible indicator of associations to a wide range of health-, stress-, well-being-, and psychosocially oriented work-related variables.
Clinical and genetic characteristics of carriers of the TP53 c.541C > T, p.Arg181Cys pathogenic variant causing hereditary cancer in patients of Arab-Muslim descent
Authors: Arnon Johnathan , Zick Aviad , Maoz Myriam , Salaymeh Nada , Gugenheim Ahinoam , Marouani MazalTov , Mor Eden , Hamburger Tamar , Saadi Nagam , Elia Anna , Ganz Gael , Fahham Duha , Meirovitz Amichay , Kadouri Luna , Meiner Vardiella , Yablonski-Peretz Tamar , Shkedi-Rafid Shiri
Published: May 2024

TP53 pathogenic variants cause Li-Fraumeni syndrome (LFS), with some variants causing an attenuated phenotype. Herein, we describe the clinical phenotype and genetic characteristics of carriers of NM_000546.6 (TP53): c.541C > T, (p.Arg181Cys) treated at Hadassah Medical Center. We retrospectively examined our genetic databases to identify all carriers of TP53 p.Arg181Cys. We reached out to carriers and their relatives and collected clinical and demographic data, lifestyle factors, carcinogenic exposures as well as additional blood samples for genetic testing and whole exome sequencing. Between 2005 and 2022 a total of 2875 cancer patients underwent genetic testing using genetic panels, whole exome sequencing or targeted TP53 assays. A total of 30 cancer patients, all of Arab-Muslim descent, were found to be carriers of TP53 p.Arg181Cys, the majority from Jerusalem and Hebron, two of which were homozygous for the variant. Carriers were from 24 distinct families of them, 15 families (62.5%) met updated Chompret criteria for LFS. Median age of diagnosis was 35 years-old (range 1–69) with cancers characteristic of LFS (16 Breast cancer; 6 primary CNS tumors; 3 sarcomas) including 4 children with choroid plexus carcinoma, medulloblastoma, or glioblastoma. A total of 21 healthy carriers of TP53 p.Arg181Cys were identified at a median age of 39 years-old (range 2–54)—19 relatives and 2 additional pediatric non-cancer patients, in which the finding was incidental. We report a shared haplotype of 350kb among carriers, limited co-morbidities and low BMI in both cancer patients and healthy carriers. There were no demographic factors or carcinogenic exposures unique to carriers who developed malignancy. Upon exome analysis no other known pathogenic variants in cancer predisposing genes were identified. TP53 p.Arg181Cys is a founder pathogenic variant predominant to the Arab-Muslim population in Jerusalem and Hebron, causing attenuated-LFS. We suggest strict surveillance in established carriers and encourage referral to genetic testing for all cancer patients of Arab-Muslim descent in this region with LFS-associated malignancies as well as family members of established carriers.
Screening for pancreatic cancer in high-risk individuals using MRI: optimization of scan techniques to detect small lesions
Authors: Boekestijn Bas , Feshtali Shirin , Vasen Hans , van Leerdam Monique E. , Bonsing Bert A. , Mieog J. Sven D. , Wasser Martin N.
Published: May 2024

Pancreatic cancer has a dismal prognosis in the general population. However, early detection and treatment of disease in high-risk individuals can improve survival, as patients with localized disease and especially patients with lesions smaller than 10 mm show greatly improved 5-year survival rates. To achieve early detection through MRI surveillance programs, optimization of imaging is required. Advances in MRI technologies in both hardware and software over the years have enabled reliable detection of pancreatic cancer at a small size and early stage. Standardization of dedicated imaging protocols for the pancreas are still lacking. In this review we discuss state of the art scan techniques, sequences, reduction of artifacts and imaging strategies that enable early detection of lesions. Furthermore, we present the imaging features of small pancreatic cancers from a large cohort of high-risk individuals. Refinement of MRI techniques, increased scan quality and the use of artificial intelligence may further improve early detection and the prognosis of pancreatic cancer in a screening setting.
Early stress exposure on zebrafish development: effects on survival, malformations and molecular alterations
Authors: Valcarce David G. , Sellés-Egea Alba , Riesco Marta F. , De Garnica María-Gracia , Martínez-Fernández Beatriz , Herráez María Paz , Robles Vanesa
Published: May 2024

The effects of stress during early vertebrate development can be especially harmful. Avoiding stressors in fish larvae is essential to ensure the health of adult fish and their reproductive performance and overall production. We examined the consequences of direct exposure to successive acute stressors during early development, including their effects on miR-29a and its targets, survival, hatching and malformation rates, larval behaviour and cartilage and eye development. Our aim was to shed light on the pleiotropic effects of early-induced stress in this vertebrate model species. Our results showed that direct exposure to successive acute stressors during early development significantly upregulated miR-29a and downregulated essential collagen transcripts col2a1a, col6a2 and col11a1a, decreased survival and increased malformation rates (swim bladder, otoliths, cardiac oedema and ocular malformations), promoting higher rates of immobility in larvae. Our results revealed that stress in early stages can induce different eye tissular architecture and cranioencephalic cartilage development alterations. Our research contributes to the understanding of the impact of stressful conditions during the early stages of zebrafish development, serving as a valuable model for vertebrate research. This holds paramount significance in the fields of developmental biology and aquaculture and also highlights miR-29a as a potential molecular marker for assessing novel larval rearing programmes in teleost species.
Postglacial evolution of the Lake Constance shelf and its relation to a 10-km long chain of submerged Neolithic mounds
Authors: Perler Dominic , Benguerel Simone , Brem Hansjörg , Gilliard Florence , Hornung Jens , Keiser Thomas , Leuzinger Urs , Schaller Sebastian , Szidat Sönke , Vogel Hendrik , Wessels Martin , Anselmetti Flavio S.
Published: May 2024

A recent bathymetric survey of Lake Constance revealed ~ 170 mounds composed of loosely deposited rocks aligned in a ~ 10-km long chain along the southern Swiss shoreline in a water depth of 3–5 m. The mounds are 10–30 m in diameter and up to 1.5 m high. Over their entire length of occurrence, the mounds are estimated to be composed of ~ 60 million individual boulders, with a total weight of ~ 78,000 t. A ground penetrating radar (GPR) survey showed that the mounds are not linked to the glacial substrate but were rather deposited artificially on the edge of a prograding shelf composed of Holocene lake sediments. Here, we present the results of a coring campaign with four piston cores along a GPR transect across one of the mounds. The cores recovered the full Holocene sedimentary succession all the way into the basal till that is overlain by lacustrine sediments dating back to ~ 14,400 cal. yrs BP. The four cores are merged into a ~ 12.4-m long composite section reflecting continuous sedimentation from the siliciclastic-dominated Late Glacial to the carbonate-rich Late Holocene. The stratigraphic horizon representing the mound’s construction was radiocarbon-dated to ~ 5600–5300 cal. yrs BP, placing them in the Neolithic period. This age was confirmed by radiocarbon dating of wood samples collected during underwater excavation of the mounds. Geochemical analysis of the Holocene sedimentary succession shows generally high carbonate contents (average of 69%). The interval from 5750 to 4950 cal. yrs BP, a part of the mound period, is characterized by a Holocene minimum in carbonate content (average of 57%) and by larger mean grain sizes. Comparing these values to those from a recent surface-sediment depth transect indicates that this was a period of rather low lake levels, which might have favoured mound construction. Correlations to nearby archaeological sites and to the general West-Central European lake-level record indicates that the mounds likely were built during a short phase of low lake levels during a general trend of climatic cooling followed by a lake-level transgression.
Should vegans have children? A response to Räsänen
Authors: Austin-Eames Louis
Published: May 2024

Joona Räsänen argues that vegans ought to be anti-natalists and therefore abstain from having children. More precisely, Räsänen claims that vegans who accept a utilitarian or rights-based argument for veganism, ought to, by parity of reasoning, accept an analogous argument for anti-natalism. In this paper, I argue that the reasons vegans have for refraining from purchasing animal products do not commit them to abstaining from having children. I provide novel arguments to the following conclusion: while there is good reason to believe that factory farming results in a net disutility and involves treating non-human animals as mere means, there is not good reason to believe that having children results in a net disutility or involves treating the children as mere means. Subsequently, I respond to what I take to be Räsänen’s underlying reasoning—that vegans are committed to abstaining from other practices which cause unnecessary suffering. I respond by arguing that this is plausibly false as various practices which cause unnecessary suffering are likely permissible, whereas factory farming is not.
Stochastic Partial Differential Equations and Invariant Manifolds in Embedded Hilbert Spaces
Authors: Bhaskaran Rajeev , Tappe Stefan
Published: May 2024

We provide necessary and sufficient conditions for stochastic invariance of finite dimensional submanifolds for solutions of stochastic partial differential equations (SPDEs) in continuously embedded Hilbert spaces with non-smooth coefficients. Furthermore, we establish a link between invariance of submanifolds for such SPDEs in Hermite Sobolev spaces and invariance of submanifolds for finite dimensional SDEs. This provides a new method for analyzing stochastic invariance of submanifolds for finite dimensional Itô diffusions, which we will use in order to derive new invariance results for finite dimensional SDEs.
Automatic evolutionary design of quantum rule-based systems and applications to quantum reinforcement learning
Authors: Cuéllar Manuel P. , Pegalajar M. C. , Cano C.
Published: May 2024

Explainable artificial intelligence is a research topic whose relevance has increased in recent years, especially with the advent of large machine learning models. However, very few attempts have been proposed to improve interpretability in the case of quantum artificial intelligence, and many existing quantum machine learning models in the literature can be considered almost as black boxes. In this article, we argue that an appropriate semantic interpretation of a given quantum circuit that solves a problem can be of interest to the user not only to certify the correct behavior of the learned model, but also to obtain a deeper insight into the problem at hand and its solution. We focus on decision-making problems that can be formulated as classification tasks and propose a method for learning quantum rule-based systems to solve them using evolutionary optimization algorithms. The approach is tested to learn rules that solve control and decision-making tasks in reinforcement learning environments, to provide interpretable agent policies that help to understand the internal dynamics of an unknown environment. Our results conclude that the learned policies are not only highly explainable, but can also help detect non-relevant features of problems and produce a minimal set of rules.
Oxidative stress and DNA alteration on the earthworm Eisenia fetida exposed to four commercial pesticides
Authors: Campani Tommaso , Casini Silvia , Maccantelli Andrea , Tosoni Filippo , D’Agostino Antonella , Caliani Ilaria
Published: May 2024

Modern agriculture is mainly based on the use of pesticides to protect crops but their efficiency is very low, in fact, most of them reach water or soil ecosystems causing pollution and health hazards to non-target organisms. Fungicide triazoles and strobilurins based are the most widely used and require a specific effort to investigate toxicological effects on non-target species. This study evaluates the toxic effects of four commercial fungicides Prosaro® (tebuconazole and prothioconazole), Amistar®Xtra (azoxystrobin and cyproconazole), Mirador® (azoxystrobin) and Icarus® (Tebuconazole) on Eisenia fetida using several biomarkers: lipid peroxidation (LPO), catalase activity (CAT), glutathione S-transferase (GST), total glutathione (GSHt), DNA fragmentation (comet assay) and lysozyme activity tested for the first time in E. fetida. The exposure to Mirador® and AmistarXtra® caused an imbalance of ROS species, leading to the inhibition of the immune system. AmistarXtra® and Prosaro®, composed of two active ingredients, induced significant DNA alteration, indicating genotoxic effects. This study broadened our knowledge of the effects of pesticide product formulations on earthworms and showed the need for improvement in the evaluation of toxicological risk deriving from the changing of physicochemical and toxicological properties that occur when a commercial formulation contains more than one active ingredient and several unknown co-formulants.
The role of environmental tax on the environmental quality in EU counties: evidence from panel vector autoregression approach
Authors: Savranlar Buket , Ertas Seyyid Ali , Aslan Alper
Published: May 2024

This study intends to analyze the influence of environmental taxes on pollution in EU-27 nations. Furthermore, energy from renewable sources consumption and urbanization are employed to clarify CO2 emissions in this study that tests the EKC hypothesis. According to the findings, an increase in environmental taxes reduces CO2 emissions by 0.14%. Also, the data supported the validity of the EKC concept. The findings of the causality test demonstrated that there is a bidirectional causal link between CO2 emissions and environmental taxes. These results reflect that environmental tax revenues contribute to sustainability as an effective policy tool in EU countries. Policies regarding environmental tax enforcement come to the fore in terms of both keeping the balance in economic activities and serving sustainability.
Correlation of fabric parameters and characteristic features of granular material behaviour in DEM in constitutive modelling
Authors: Khayyer Farid , Rahman Md Mizanur , Karim Md Rajibul
Published: May 2024

The anisotropic microstructure of granular materials has a profound effect on their macroscopic behaviour and can be characterised using a fabric tensor. To include of fabric in the critical state theory (CST), anisotropic critical state theory (ACST) was proposed by modifying the state parameter $$(\psi )$$

(
ψ
)

of CST to a fabric-dependent dilatancy state parameter $$(\upzeta )$$

(
ζ
)

. Noteworthy that $$\uppsi$$
ψ
showed a very strong correlation with characteristic features (e.g. instability, phase transformation and characteristic state) of macroscopic behaviour and, as a result, it has been adopted in many constitutive models. While $$\upzeta$$
ζ
aided the inclusion of fabric in ACST models, the correlation between $$\upzeta$$
ζ
and characteristic features has not been evaluated in detail yet, although a large number of works are found on micromechanics and fabric only. In this study, a large number of discrete element method simulations for drained and undrained triaxial were conducted to evaluate the correlation between $$\upzeta$$
ζ
and characteristic features. To this purpose, the correlation between stress ratio and both classic and dilatancy state parameter ($$\psi$$
ψ
and $$\upzeta$$
ζ
) were studied in important characteristic features (e.g. instability, phase transformation and characteristic state). It was found that this correlation was improved using $$\upzeta$$
ζ
which might be due to the inclusion of fabric in our model. This observation is new and significant for inclusion of fabric evolution in constitutive modelling.
The Effects of Fingolimod (FTY720) on Leukocyte Subset Circulation cannot be Behaviourally Conditioned in Rats
Authors: Jakobs Marie , Hörbelt-Grünheidt Tina , Hadamitzky Martin , Bihorac Julia , Salem Yasmin , Leisengang Stephan , Christians Uwe , Schniedewind Björn , Schedlowski Manfred , Lückemann Laura
Published: May 2024

Suppression of immune functions can be elicited by behavioural conditioning using drugs such as cyclosporin A or rapamycin. Nevertheless, little is known about the underlying mechanisms and generalisability of this phenomenon. Against this background, the present study investigated whether the pharmacological properties of fingolimod (FTY720), an immunosuppressive drug widely applied to treat multiple sclerosis, can be conditioned in rats by means of taste-immune associative learning. For this purpose, a conditioned taste avoidance paradigm was used, pairing the presentation of a novel sweet drinking solution (saccharin or sucrose) as conditioned stimulus (CS) with therapeutically effective doses of FTY720 as unconditioned stimulus (US). Subsequent re-exposure to the CS at a later time point revealed that conditioning with FTY720 induced a mild conditioned taste avoidance only when saccharin was employed as CS. However, on an immunological level, neither re-exposure with saccharin nor sucrose altered blood immune cell subsets or splenic cytokine production. Despite the fact that intraperitonally administered FTY720 could be detected in brain regions known to mediate neuro-immune interactions, the present findings show that the physiological action of FTY720 is not inducible by mere taste-immune associative learning. Whether conditioning generalises across all small-molecule drugs with immunosuppressive properties still needs to be investigated with modified paradigms probably using distinct sensory CS. Moreover, these findings emphasize the need to further investigate the underlying mechanisms of conditioned immunomodulation to assess the generalisability and usability of associative learning protocols as supportive therapies in clinical contexts.

Graphical Abstract