bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal intravital imaging of the bone marrow for analysis of the race for the surface in a murine osteomyelitis model
Authors: Xie Chao , Ren Youliang , Weeks Jason , Rainbolt Joshua , Kenney Howard M. , Xue Thomas , Allen Faith , Shu Ye , Tay Allie J. H. , Lekkala Sashank , Yeh Shu‐Chi A. , Muthukrishnan Gowrishankar , Gill Ann L. , Gill Steven R. , Kim Minsoo , Kates Stephen L. , Schwarz Edward M.
Published: October 2023

Critical knowledge gaps of orthopedic infections pertain to bacterial colonization. The established dogma termed the Race for the Surface posits that contaminating bacteria compete with host cells for the implant post‐op, which remains unproven without real‐time in vivo evidence. Thus, we modified the murine longitudinal intravital imaging of the bone marrow (LIMB) system to allow real‐time quantification of green fluorescent protein (GFP+) host cells and enhanced cyan fluorescent protein (ECFP+) or red fluorescent protein (RFP+) methicillin‐resistant Staphylococcus aureus (MRSA) proximal to a transfemoral implant. Following inoculation with ~105 CFU, an L‐shaped metal implant was press‐fit through the lateral cortex at a 90° angle ~0.150 mm below a gradient refractive index (GRIN) lens. We empirically derived a volume of interest (VOI) = 0.0161 ± 0.000675 mm3 during each imaging session by aggregating the Z‐stacks between the first (superior) and last (inferior) in‐focus LIMB slice. LIMB postimplantation revealed very limited bacteria detection at 1 h, but by 3 h, 56.8% of the implant surface was covered by ECFP+ bacteria, and the rest were covered by GFP+ host cells. 3D volumetric rendering of the GFP+ and ECFP+ or RFP+ voxels demonstrated exponential MRSA growth between 3 and 6 h in the Z‐plane, which was validated with cross‐sectional ex vivo bacterial burden analyses demonstrating significant growth by ~2 × 104 CFU/h on the implant from 2 to 12 h post‐op (p < 0.05; r2 > 0.98). Collectively, these results show the competition at the surface is completed by 3 h in this model and demonstrate the potential of LIMB to elucidate mechanisms of bacterial colonization, the host immune response, and the efficacy of antimicrobials.
Knowledge of free radicals and antioxidants in dermatology in the general population
Authors: Dahan Serge , Khalouf Randa , Salcedo Nikki , Taieb Charles , Gassia Veronique
Published: October 2023

Background

Excessive production of free radicals may cause oxidative stress. In dermatology, free radicals are implicated in the etiopathogenesis of various dermatoses, in the onset of cutaneous neoplasias, and in the aging process. Few data are available on the knowledge about free radicals in the general population.

Objectives

To investigate knowledge of free radicals and antioxidants in a large sample of the French general population, with a particular focus on skin aging.

Methods

Data were collected through a web‐based online survey of a representative sample of the French population aged 18 years or more. The survey included seven questions on the role of free radicals in the human body, their possible risk factors, and the role of antioxidants in dermocosmetics.

Results

Data were collected on 15,050 participants, with 52.8% of men and mean age of 46.9 years. About half of the participants reported knowing free radicals, and more than half of them were aware that free radicals may be harmful to the body and cause cell oxidation. Among factors causing the production of free radicals, the most frequent answer was UV, followed by smoking, pollution, and alcohol. More than three‐quarter of participants were aware of the role of free radicals in skin aging, and about 60% of the existence of protective antioxidant treatments. Knowledge of free radicals was reported more frequently by women than men and increased with age and educational level.

Conclusions

A significant proportion of the French population seems unfamiliar with the term free radicals and antioxidants. This is perhaps due to the ambiguity that exists within the scientific community about how to prevent oxidative stress and whether these mechanisms produce clinical results.
Long latency reflexes of the median nerves in healthy adults
Authors: Winkel Antony , Cook Mark , Roberts Leslie
Published: October 2023

Introduction/Aims

Long latency reflexes (LLRs) are late responses in nerve conduction studies seen after peripheral nerve stimulation during submaximal muscle contraction. They follow a short latency reflex, also known as the H reflex, and are thought to involve transcortical pathways, providing a measure of proximal nerve and central conduction. For this reason, they have been evaluated in several central nervous system diseases, but reference values are not widely published and are mostly based on old studies with very small numbers of participants. Therefore, in this work we aim to provide comprehensive reference values for LLR testing.

Methods

LLRs were tested in a cohort of 100 healthy participants, testing the median nerve bilaterally.

Results

Mean latencies for short latency reflex (SLR), LLR1, LLR2, and LLR3 were 27.00, 38.50, 47.60, and 67.34 milliseconds, respectively. The allowable side‐to‐side difference was approximately 3 to 4 milliseconds. No significant sex‐related differences were seen. Height correlated moderately with the SLR latency, but only weakly with LLR1, LLR2, and LLR3.

Discussion

This work provides normal LLR values for comparison with future studies in disease. The technique used may allow for improved evaluation of central nervous system or proximal peripheral nerve disorders.
Postprandial splenic stiffness changes on magnetic resonance elastography in a young healthy population
Authors: Obrzut Marzanna , Atamaniuk Vitaliy , Ehman Richard L. , Yin Meng , Cholewa Marian , Gutkowski Krzysztof , Domka Wojciech , Obrzut Bogdan
Published: October 2023

Magnetic resonance elastography (MRE) is an accurate noninvasive diagnostic tool for assessing the stiffness of parenchymal organs, including the spleen. However, this measurement may be biased due to postprandial changes in splenic stiffness. The aim of the current study was to evaluate postprandial changes in spleen stiffness assessed by MRE in a large sample of healthy volunteers. This was a prospective institutional research ethics board‐approved study. Healthy volunteers with no history of liver disease were recruited for an MRE test and blood draw from December 2018 to July 2019. Each participant underwent spleen MRE after at least 4 h of fasting and again 30 min after a 1000 kcal meal. Also, 14 randomly selected volunteers underwent additional MRE examinations at 1.5 and 2.5 h after food intake. The MRE data were acquired at 60 Hz using a 1.5‐T MRI scanner. The spleen stiffness was assessed using a weighted mean of stiffness values from regions of interest manually drawn on three to five spleen slices. Spearman's rank correlation, Wilcoxon signed‐rank, Friedman, and Mann–Whitney tests were used for statistical analysis. A total of 100 volunteers met the inclusion criteria and were eventually enrolled in this study (age 23 ± 2 years; 65 women). The mean spleen stiffness for the whole group increased by 7.9% (p < 0.001) from the mean ± SD value of 5.09 ± 0.63 (95% CI: 4.96–5.21) kPa in the fasting state to 5.47 ± 0.66 (95% CI 5.34–5.60) kPa 30 min after the meal and then gradually decreased. However, even 2 h 30 min after the meal, the spleen stiffness was higher than in the fasting state. This difference was statistically significant at p less than 0.001. It was concluded that meal intake results in a statistically significant elevation of spleen stiffness that persists for 2.5 h. This finding supports the recommendation for routine fasting for more than 2.5 h prior to assessing MRE‐based spleen stiffness.
Variational models for pattern formation in biomembranes—A Γ‐convergence result
Authors: Pešić Anastasija
Published: October 2023

Biological membranes are thin structures that are composed of various components. The different components often form microdomains, called lipid rafts, that are arranged in complex patterns. To explain this pattern formation, variational models based on Cahn–Hilliard‐type energies have been introduced that couple the local composition of the membrane to its local curvature, which renders the resulting functionals nonlocal. In this note, we review and extend recent qualitative results on related variational models. This includes a technique to deal with Neumann‐boundary conditions in the construction of a recovery sequence.
Curved grid‐scored foam core sandwich composites under low‐velocity impact loads: Effects of curvature, stacking sequence, and core finishing
Authors: Balıkoğlu Fatih
Published: October 2023

The objective of this paper is to experimentally investigate how material and geometric parameters, including face sheet layup, curvature, and core finishing, affect the contact force‐displacement behavior, absorbed energy, and damage modes of curved sandwich composites with grid‐scored foam under low‐velocity impact loads. An instrumented drop‐weight testing machine with a hemispherical impactor was used to perform low‐velocity impact tests at different energy levels. Angled‐ply stacking had the maximum contact force and impact resistance for low curvature radii. In the event of penetration, the impact energy absorption of all curved sandwich panels increased as the curvature increased. The core finishing influenced the contact forces of the curved and flat sandwich panels but not the penetration energy. The curvature and face sheet layups affected the delamination size and pattern. Angle‐ply and cross‐ply face sheets with the smallest and maximum radius of curvature, respectively, decreased penetration depth. The resin‐filled channels reduced foam cell impact damage and face‐core debonding. LVI penetration resistance was found to be highest for angle‐ply stacking and knife‐cut foam at small curvature radii. The proposed research will also provide naval designers with valuable insight into the impact response of sandwich structures used in curved parts of the hull and deck.

Highlights

The effect of curvature on the LVI responses varied due to face sheet layups.

Core finishing affected contact forces, but not the absorbed energy.

Curvature and face sheet layups affected the damage modes.

Resin‐filled channels limited damage area and acted as stoppers for debonding.
Low‐Loss Sr2Ti9O20‐Filled Butyl Rubber Composites for Miniaturized Flexible Microwave Substrate Applications
Authors: Muhammed Hunize C. V. , Arun Shaji B. K. , Joseph M. A. , Pradeep Anju , Murali K. P.
Published: October 2023

Low‐loss Sr2Ti9O20 (STO)/butyl rubber (BR) composites have been prepared by mixing and hot pressing. X‐ray diffraction and energy‐dispersive spectroscopy are employed to investigate the phases contained in the STO filler, and the microstructural characteristics of the composites are discovered using scanning electron microscopy. The STO/BR composites demonstrate a high relative permittivity of 10.98 and a low loss of 0.003 at 10 GHz, corresponding to an optimum filler volume fraction of 45%. In addition, a low coefficient of thermal expansion of 50.72 ppm °C−1 and a high thermal conductivity of 0.9603 W m−1 K−1 have been found for the optimum composition, with an acceptable moisture absorption of 0.071%. The obtained composites can be employed for miniaturized, flexible radio‐frequency substrate applications.
Visible‐Light‐Initiated Dehydrogenative Cyclization of o‐Aminobenzamide and Alcohols for Coproduction of Quinazolinones and Hydrogen over PtS/ZnIn2S4
Authors: Du Xiao , Wang Jiaqi , Liu Hurunqing , Yuan Rusheng , Li Zhaohui
Published: October 2023

PtS/ZnIn2S4 nanocomposites are obtained via a microwave‐assisted synthesis followed by a photoreduction. The resultant PtS/ZnIn2S4 nanocomposites are used as an effective multifunctional photocatalyst for the reaction between alcohols and o‐aminobenzamide to coproduce quinazolinones and hydrogen under visible light, via a cascade alcohols/aldehydes transformation, condensation between aldehydes and o‐aminobenzamide, as well as the dehydrogenation/cyclization to produce quinazolinones. PtS acts as an efficient cocatalyst to promote the dehydrogenation of both the alcohols and the condensation intermediates for the production of quinazolinones. An almost complete conversion of o‐aminobenzamide was achieved in 24 h, with a yield of 98.8% to 2‐phenyl‐quinazline‐4(3H)‐one and quantitative hydrogen produced over PtS/ZnIn2S4 after irradiated for 24 h. The apparent quantum yield at 450 nm is determined to 15.2%. The superior activity observed over PtS/ZnIn2S4 nanocomposite as compared with that over either NiS/ZnIn2S4 or MoS2/ZnIn2S4 can be ascribed to a moderate binding between PtS and the surface adsorbed H*. This study supplies an effective, green, and atom‐economic strategy for the synthesis of quinazolinones with coproduction of hydrogen under visible light. This work also demonstrates the high potential of fabrication of metal sulfide‐based multifunctional catalysts for light‐driven one‐pot tandem/cascade reactions.
Focus on Math and Reading Test Score Inequalities
Authors: Thomas Hoben
Published: October 2023

Worldwide there has been recognition that boys’ and girls’ reading and math test score distributions are different. What has not been recognized is precisely how these distributions differ.
Theorie der Soziologie gemeinsamen Musizierens
Authors: Vollmer Theresa
Published: October 2023

Die vorliegende Promotion widmet sich der soziologischen Perspektivierung gemeinsamen Musizierens, die anhand der empirischen Untersuchung der Streichensembles vorgenommen wird. Die Wahl des Forschungsgegenstandes ist durch grundlagen- wie sozialtheoretische Erkenntnisinteressen inspiriert, die einen Beitrag zu einer beinahe anthropologischen Fragestellung leisten soll: „Wie koordinieren sich Menschen körperlich und zeichenhaft?“. Letztgenannte ist derart grundlegend formuliert, dass sie im Grunde jede Art der zwischenmenschlichen Begegnung adressiert.
Die Ethnographie der Streichensembles. Zu Wissen, Hörwelt und Klangwelt gemeinsamen Musizierens
Authors: Vollmer Theresa
Published: October 2023

Das Kapitel V widmet sich der Darstellung der Ethnographie der Streichensembles. Dieselbe ist in zwei Teile untergliedert.
Die HörKlangwelt der Soziologie gemeinsamen Musizierens
Authors: Vollmer Theresa
Published: October 2023

Die Forschungsfrage der Ethnographie gemeinsamen Musizierens lautet: „Wie machen Klassisch ausgebildete Musiker:innen mit ihren Instrumenten und Noten gemeinsam Musik in Streichensembles und erleben sie dabei?“ In diesem Kapitel werden die Ergebnisse der Untersuchung zusammengetragen und integriert, um die Forschungsfrage zu beantworten.
Evaluative audiometry after cochlear implant provision
Authors: Dziemba Oliver C. , Merz Stephan , Hocke Thomas
Published: October 2023

Background

One of the main treatment goals in cochlear implant (CI) patients is to improve speech perception. One of the target parameters is speech intelligibility in quiet. However, treatment results show a high variability, which has not been sufficiently explained so far. The aim of this noninterventional retrospective study was to elucidate this variability using a selected population of patients in whom etiology was not expected to have a negative impact on postoperative speech intelligibility.

Materials and methods

Audiometric findings of the CI follow-up of 28 adult patients after 6 months of CI experience were evaluated. These were related to the preoperative audiometric examination and evaluated with respect to a recently published predictive model for the postoperative monosyllabic score.

Results

Inclusion of postoperative categorical loudness scaling and hearing loss for Freiburg numbers in the model explained 55% of the variability in fitting outcomes with respect to monosyllabic word recognition.

Conclusion

The results of this study suggest that much of the cause of variability in fitting outcomes can be captured by systematic postoperative audiometric checks. Immediate conclusions for CI system fitting adjustments may be drawn from these results. However, the extent to which these are accepted by individual patients and thus lead to an improvement in outcome must be subject of further studies, preferably prospective.
In Search of Mercury Lost from Sediments in a Previously Contaminated Coastal Area, Harboøre Tange, Denmark
Authors: Bjerregaard Poul , Jensen Christina Lisby , Juhl Anna Victoria Rode , Markussen Alexander Jacob Rahbek , Poulsen Sanne Ravnholt
Published: October 2023

Concentrations of mercury in sediment and benthic invertebrate fauna of Nissum Broad, North-western Jutland, Denmark were investigated. The western coast of Nissum Broad is Harboøre Tange, along which heavy mercury contamination - caused by discharge from production of mercury containing seed dressers in the 1950 and 1960s – was documented in the 1980s. Recent investigations showed marked decreases in mercury contamination in the near shore sediments along Harboøre Tange since the 1980s and the present investigation was initiated to learn if the loss of mercury from Harboøre Tange had led to an increased mercury contamination in the neighbouring marine area, Nissum Broad. Mercury concentrations in the surface sediment correlated with the content of organic matter and the slope of the regression is a good indicator for the degree of mercury contamination. Average mercury concentrations in the upper 5 cm of the sediments ranged between 0.9 and 71 ng g− 1 dry weight (dw) with only 1 station exceeding the Background Assessment Concentration of 70 ng g− 1 dw. Average mercury concentrations in blue mussels Mytilus edulis (169–260 ng g− 1 dw) and periwinkles Littorina littorea (66–203 ng g− 1 dw) exceeded those in uncontaminated areas and the Environmental Quality Standard of approximately 100 ng g− 1 dw. Present sediment mercury concentrations in Nissum Broad are approximately half of what they were in the 1980s, rendering it unlikely that mercury lost from Harboøre Tange has been deposited there. Sediment and organism concentrations did not show any correlation.
Image‐based robotic‐arm assisted unicompartmental knee arthroplasty provides high survival and good‐to‐excellent clinical outcomes at minimum 10 years follow‐up
Authors: Zambianchi Francesco , Seracchioli Stefano , Franceschi Giorgio , Cuoghi Costantini Riccardo , Malatesta Alessandro , Barbo Giovanni , Catani Fabio
Published: October 2023

Purpose

The purpose of the present study was to determine the incidence of revision and report on clinical outcomes at a minimum of 10 years follow‐up in patients who had received a medial unicompartmental knee arthroplasty (UKA) with an three‐dimensional image‐based robotic system.

Methods

A total of 239 patients (247 knees), who underwent medial robotic‐arm assisted (RA)‐UKA at a single center between April 2011 and June 2013, were assessed. The mean age at surgery was 67.0 years (SD 8.4). Post‐operatively, patients were administered the Forgotten Joint Score‐12 (FJS‐12) and asked about their satisfaction (from 1 to 5). Post‐operative complications were recorded. Failure mechanisms, revisions and reoperations were collected. Kaplan–Meier survival curves were calculated, considering revision as the event of interest.

Results

A total of 188 patients (196 knees) were assessed at a mean follow‐up of 11.1 years (SD 0.5, range 10.0–11.9), resulting in a 79.4% follow‐up rate. Seven RA‐UKA underwent revision, resulting in a survivorship rate of 96.4% (CI 94.6%–99.2%). Causes of revision included aseptic loosening (2 cases), infection (1 case), post‐traumatic (1 case), and unexplained pain (3 cases). The mean FJS‐12 and satisfaction were 82.2 (SD 23.9) and 4.4 (SD 0.9), respectively. Majority of cases (174/196, 88.8%) attained the Patient Acceptable Symptoms State (PASS, FJS‐12 > 40.63). Male subjects had a higher probability of attaining a “forgotten joint” (p < 0.001) and high satisfaction (equal to 5, p < 0.05), when compared to females.

Conclusions

Three‐dimensional image‐based RA‐UKA demonstrated high implant survivorship and good‐to‐excellent clinical outcomes at minimum 10 years follow‐up. Pain of unknown origin represented the most common reason for RA‐UKA revision.

Level of evidence

III.
IL-10 plus the EASIX score predict bleeding events after anti-CD19 CAR T-cell therapy
Authors: Wang Xindi , Li Chenggong , Luo Wenjing , Zhang Yinqiang , Huang Zhongpei , Xu Jia , Mei Heng , Hu Yu
Published: October 2023

Chimeric antigen receptor (CAR) T-cell-associated coagulopathy can cause bleeding events. To explore risk factors for hemorrhage after CAR T-cell therapy, we retrospectively analyzed routine indicators in 56 patients with non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia who received anti-CD19 CAR T-cell therapy. Disturbance of coagulation occurred mainly within one month post infusion, especially on day 7 and 14. The cumulative incidence of bleeding events within one month was 32.8%, with the median onset of 7 (range, 0–28) days. All bleeding events were grade 1–3. Patients who experienced bleeding events within one month had longer prothrombin time, higher IL-6, higher IL-10, and lower platelets before lymphodepletion. There were also correlations among coagulation-, inflammatory-, and tumor burden-related markers. Multi-variate analysis showed IL-10 (> 7.98 pg/mL; adjusted odds ratio [OR], 13.84; 95% confidence interval [CI], 2.03–94.36; P = 0.007) and the endothelial activation and stress index (EASIX, defined as dehydrogenase [U/L] × creatinine [mg/dL] / platelets [×109 cells/L]; >7.65; adjusted OR, 7.06; 95% CI, 1.03–48.23; P = 0.046) were significant risk factors for bleeding events. IL-10 plus the EASIX defined three risk groups for bleeding events with cumulative incidence of 100% (hazard ratio [HR], 14.47; 95% CI, 2.78–75.29; P < 0.0001), 38.5% (HR, 3.68; 95% CI, 0.82–16.67; P = 0.089), and 11.8% (reference), respectively. Future studies are needed to verify the risk assessment models for bleeding events after CAR T-cell treatment in larger cohorts.
Health inequalities among young workers: the mediating role of working conditions and company characteristics
Authors: Reuter Marvin , Pischke Claudia R. , Rigo Mariann , Diehl Katharina , Spallek Jacob , Richter Matthias , Hövener Claudia , Dragano Nico
Published: October 2023

Objective

Few studies have investigated health inequalities among young workers. The objectives of this study are to assess the extent of health inequalities in a sample of job starters and to explore the contribution of job demands and organisational factors.

Methods

We analyze data from the BIBB/BAuA Youth Employment Survey 2012. The cross-sectional survey includes a representative sample of 3214 German employees, apprentices, and trainees aged 15–24 years. Individuals were grouped by their years of schooling into low (< 12 years) and high levels of education (≥ 12 years). Regression analysis estimated the link between education and four health outcomes: self-rated health, number of health events, musculoskeletal symptoms, and mental health problems over the last 12 months. Counterfactual mediation analysis tested for indirect effects of education via working conditions (i.e., physical and psychosocial job demands) and company characteristics (i.e., company size, health prevention measures, financial situation, downsizing). All analyses were adjusted for age, sex, nationality, region, working hours, job tenure, employment relationship, and economic sector.

Results

Highly educated workers reported better self-rated health (b = 0.24, 95% CI 0.18–0.31) and lower numbers of health events (Rate Ratio (RR) = 0.74, 95% CI 0.67–0.82), musculoskeletal symptoms (RR = 0.73, 95% CI 0.66–0.80) and mental health problems (RR = 0.84, 95% CI 0.76–0.93). Total job demands explained between 21.6% and 87.2% of the educational differences (depending on health outcome). Unfavourable company characteristics were associated with worse health, but showed no or only small mediation effects.

Conclusions

Health inequalities are already present at the early working career due to socio-economically stratified working hazards. To enhance prevention measures that aim at reducing inequalities in workplace health, we propose shifting attention towards earlier stages of life.
Epigenetic modifications evidenced by isolation of proteins on nascent DNA and immunofluorescence in hydroxyurea-treated root meristem cells of Vicia faba
Authors: Żabka Aneta , Gocek Natalia , Polit Justyna Teresa , Maszewski Janusz
Published: October 2023

Main conclusion

By implementation of the iPOND technique for plant material, changes in posttranslational modifications of histones were identified in hydroxyurea-treated root meristem cells of Vicia.

Replication stress (RS) disrupts or inhibits replication forks and by altering epigenetic information of the newly formed chromatin can affect gene regulation and/or spatial organisation of DNA. Experiments on Vicia faba root meristem cells exposed to short-term treatment with 3 mM hydroxyurea (HU, an inhibitor of DNA replication) were aimed to understand epigenetic changes related to RS. To achieve this, the following histone modifications were studied using isolation of proteins on nascent DNA (iPOND) technique (for the first time on plant material) combined with immunofluorescence labeling: (i) acetylation of histone H3 at lysine 56 (H3K56Ac), (ii) acetylation of histone H4 at Lys 5 (H4K5Ac), and (iii) phosphorylation of histone H3 at threonine 45 (H3T45Ph). Certainly, the implementation of the iPOND method for plants may prove to be a key step for a more in-depth understanding of the cell's response to RS at the chromatin level.
A novel reinforcement learning-based reptile search algorithm for solving optimization problems
Authors: Ghetas Mohamed , Issa Mohamed
Published: October 2023

This work proposes a novel reptile search algorithm (RSA) to solve optimization problems called reinforcement reptile search algorithm (RLRSA). The basic RSA performs exploitation through highly walking in the first half of searching process while the exploration phase is executed through the hunting phase in the second half. Therefore, the algorithm is not able to balance exploration and exploitation and this behavior results in trapping in local optima. A novel learning method based on reinforcement learning and Q-learning model is proposed to balance the exploitation and exploration phases when the solution starts deteriorating. Furthermore, the random opposite-based learning (ROBL) is introduced to increase the diversity of the population and so enhance the obtained solutions. Twenty-three typical benchmark functions, including unimodal, multimodal and fixed-dimension multimodal functions, were employed to assess the performance of RLRSA. According to the findings, the RLRSA method surpasses the standard RSA approach in the majority of benchmark functions evaluated, specifically in 12 out of 13 unimodal functions, 9 out of 13 multimodal functions, and 8 out of 10 fixed multimodal functions. Furthermore, the RLRSA is applied to vessel solve pressure and tension/compression spring design problems. The results show that RLRSA significantly found the solution with minimum cost. The experimental results reveal the superiority of the RLRSA compared to RSA and other optimization methods in the literature.
Identification of monogenic diabetes in an Australian cohort using the Exeter maturity-onset diabetes of the young (MODY) probability calculator and next-generation sequencing gene panel testing
Authors: De Sousa Sunita M. C. , Wu Kathy H. C. , Colclough Kevin , Rawlings Lesley , Dubowsky Andrew , Monnik Melissa , Poplawski Nicola , Scott Hamish S. , Horowitz Michael , Torpy David J.
Published: October 2023

Aims

This study aims to describe the prevalence of monogenic diabetes in an Australian referral cohort, in relation to Exeter maturity-onset diabetes of the young (MODY) probability calculator (EMPC) scores and next-generation sequencing with updated testing where relevant.

Methods

State-wide 5-year retrospective cohort study of individuals referred for monogenic diabetes genetic testing.

Results

After excluding individuals who had cascade testing for a familial variant (21) or declined research involvement (1), the final cohort comprised 40 probands. Incorporating updated testing, the final genetic result was positive (likely pathogenic/pathogenic variant) in 11/40 (27.5%), uncertain (variant of uncertain significance) in 8/40 (20%) and negative in 21/40 (52.5%) participants. Causative variants were found in GCK, HNF1A, MT-TL1 and HNF4A. Variants of uncertain significance included a novel multi-exonic GCK duplication. Amongst participants with EMPC scores ≥ 25%, a causative variant was identified in 37%. Cascade testing was positive in 9/10 tested relatives with diabetes and 0/6 tested relatives with no history of diabetes.

Conclusions

Contemporary genetic testing produces a high yield of positive results in individuals with clinically suspected monogenic diabetes and their relatives with diabetes, highlighting the value of genetic testing for this condition. An EMPC score cutoff of ≥ 25% correctly yielded a positive predictive value of ≥ 25% in this multiethnic demographic. This is the first Australian study to describe EMPC scores in the Australian clinic setting, albeit a biased referral cohort. Larger studies may help characterise EMPC performance between ethnic subsets, noting differences in the expected probability of monogenic diabetes relative to type 2 diabetes.
Generation climate crisis, COVID-19, and Russia–Ukraine-War: global crises and mental health in adolescents
Authors: Lass-Hennemann Johanna , Sopp M. Roxanne , Ruf Norma , Equit Monika , Schäfer Sarah K. , Wirth Benedikt E. , Michael Tanja
Published: October 2023

Climate change, COVID-19, and the Russia-Ukraine War are some of the great challenges of our time. These global crises affect young people in a particularly vulnerable phase of their lives. The current study aimed to assess the impact of these crises on mental health (depression, anxiety, and health-related quality of life) in secondary school students in Germany. Furthermore, we assessed known predictors of mental health, such as socio-economic factors, individual life stressors, and resilience factors (self-efficacy, expressive flexibility) as covariates. In our sample of 3998 pupils, pandemic- and climate-related distress were linked to greater depression and anxiety and reduced health-related quality of life. War-related distress was associated with greater anxiety. Critically, these associations remained significant after controlling for all covariates, supporting the incremental predictive value of the crises measures. The study reveals a significant impact of the crises on the mental health of the current generation of adolescents. As such it suggests that mental health policies should include interventions that help youth to cope with the stress caused by the crises.
A preliminary model for optimal control of moisture content in unsaturated soils
Authors: Berardi Marco , Difonzo Fabio V. , Guglielmi Roberto
Published: October 2023

In this paper we introduce an optimal control approach to Richards’ equation in an irrigation framework, aimed at minimizing water consumption while maximizing root water uptake. We first describe the physics of the nonlinear model under consideration, and then develop the first-order necessary optimality conditions of the associated boundary control problem. We show that our model provides a promising framework to support optimized irrigation strategies, thus facing water scarcity in irrigation. The characterization of the optimal control in terms of a suitable relation with the adjoint state of the optimality conditions is then used to develop numerical simulations on different hydrological settings, that support the analytical findings of the paper.
Pseudoreplication in Primate Communication Research: 10 Years On
Authors: Whitehouse J. , Clark P. R. , Micheletta J. , Liebal K. , Slocombe K. E. , Waller B. M.
Published: October 2023

Pseudoreplication is the statistical error of collecting numerous datapoints from a single unit (such as an individual), which are not independent, and applying statistical methods that assume independence of data. Importantly, pseudoreplication increases the chances of Type 1 errors (i.e., false positives), bringing findings and conclusions based on pseudoreplicated analyses into question. Ten years ago, Waller et al. (2013) published a paper highlighting the prevalence of statistical pseudoreplication throughout the nonhuman primate communication literature. In this current study, we examined the literature published since the original publication (between 2009 and 2020; 348 papers) to assess whether pseudoreplication is still as widespread as it was, if it has become more problematic, or if the field is beginning to overcome this issue. We find that there has been a significant decrease in pseudoreplication over the past ten years (38.6% then, compared with 23.0% now). This reduction in pseudoreplication appears to be associated with an increase in the use of multilevel models throughout primatology (which allow for nonindependent data to be nested appropriately). Pseudoreplication was historically more prevalent in research using observational (vs. experimental) methods and those working with wild (vs. captive) primates. However, these biases do not seem to exist in more recent literature with a more comparable likelihood of pseudoreplication seen across the field regardless of methods. Although these current findings relate specifically to primate communication research, we think they will translate broadly across nonhuman communication research, and throughout biology. We continue to emphasise the need to monitor these issues, as although now seen at much lower rates, pseudoreplication is still present and therefore potentially impacting the accuracy of findings.
Regularising Inverse Problems with Generative Machine Learning Models
Authors: Duff M. A. G. , Campbell N. D. F. , Ehrhardt M. J.
Published: October 2023

Deep neural network approaches to inverse imaging problems have produced impressive results in the last few years. In this survey paper, we consider the use of generative models in a variational regularisation approach to inverse problems. The considered regularisers penalise images that are far from the range of a generative model that has learned to produce images similar to a training dataset. We name this familygenerative regularisers. The success of generative regularisers depends on the quality of the generative model and so we propose a set of desired criteria to assess generative models and guide future research. In our numerical experiments, we evaluate three common generative models, autoencoders, variational autoencoders and generative adversarial networks, against our desired criteria. We also test three different generative regularisers on the inverse problems of deblurring, deconvolution, and tomography. We show that restricting solutions of the inverse problem to lie exactly in the range of a generative model can give good results but that allowing small deviations from the range of the generator produces more consistent results. Finally, we discuss future directions and open problems in the field.
Molecular mechanism of paraquat-induced ferroptosis leading to pulmonary fibrosis mediated by Keap1/Nrf2 signaling pathway
Authors: Yang Xiaoxia , Xiao Ping , Shi Xiaofeng
Published: October 2023

Paraquat (PQ) is a widely used and highly toxic pesticide that is often actively ingested and causes pulmonary fibrosis in patients. Ferroptosis is a regulated form of non-apoptotic cell death associated with iron-dependent lipid peroxidation. Previous studies have shown that ferroptosis is involved in the occurrence and development of acute lung injury (ALI). In this study, a model rat with inflammatory response, oxidative stress, lipid peroxidation, and pulmonary fibrosis was successfully established by PQ administration. The occurrence of ferroptosis in PQ model rats was confirmed by TUNEL staining, iron ion detection, and Ferroptosis related biomarkers detection. Western blotting (WB) and real-time PCR (RT-PCR) showed that the expression of Keap1 was significantly up-regulated and the expression of Nrf2 was significantly down-regulated in the lung tissue of PQ rats. Further transcriptomics and proteomics confirmed: (1) Enrichment of molecular processes related to iron ion binding; (2) Keap1 may promote Nrf2 ubiquitination and lead to Nrf2 degradation; (3) There is functional enrichment in ferroptosis related pathways. Our results suggest that PQ can regulate Keap1/Nrf2 signaling pathway, leading to increased lipid peroxidation and abnormal iron uptake, thereby inducing iron death and exacerbating the progression of pulmonary fibrosis. Our study provides new insights into PQ-induced pulmonary fibrosis.

Graphical abstract
Neuroprotective Effects of Melittin Against Cerebral Ischemia and Inflammatory Injury via Upregulation of MCPIP1 to Suppress NF-κB Activation In Vivo and In Vitro
Authors: Xing Xing , Zhang Xiangjian , Fan Jingyi , Zhang Cong , Zhang Lan , Duan Ruisheng , Hao Hongyu
Published: October 2023

Melittin, a principal constituent of honeybee venom, exhibits diverse biological effects, encompassing anti-inflammatory capabilities and neuroprotective actions against an array of neurological diseases. In this study, we probed the prospective protective influence of melittin on cerebral ischemia, focusing on its anti-inflammatory activity. Mechanistically, we explored whether monocyte chemotactic protein-induced protein 1 (MCPIP1, also known as ZC3H12A), a recently identified zinc-finger protein, played a role in melittin-mediated anti-inflammation and neuroprotection. Male C57/BL6 mice were subjected to distal middle cerebral artery occlusion to create a focal cerebral cortical ischemia model, with melittin administered intraperitoneally. We evaluated motor functions, brain infarct volume, cerebral blood flow, and inflammatory marker levels within brain tissue, employing quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and western blotting. In vitro, an immortalized BV-2 microglia culture was stimulated with lipopolysaccharide (LPS) to establish an inflammatory cell model. Post-melittin exposure, cell viability, and cytokine expression were examined. MCPIP1 was silenced using siRNA in LPS-induced BV-2 cells, with the ensuing nuclear translocation of nuclear factor-κB assessed through cellular immunofluorescence. In vivo, melittin enhanced motor functions, diminished infarction, fostered blood flow restoration in ischemic brain regions, and markedly inhibited the expression of inflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α, and nuclear factor-κB). In vitro, melittin augmented MCPIP1 expression in LPS-induced BV-2 cells and ameliorated inflammation-induced cell death. The neuroprotective effect conferred by melittin was attenuated upon MCPIP1 knockdown. Our findings establish that melittin-induced tolerance to ischemic injury is intrinsically linked with its anti-inflammatory capacity. Moreover, MCPIP1 is, at the very least, partially implicated in this process.
Can computerized rumen mucosal colorimetry serve as an effective field test for managing subacute ruminal acidosis in feedlot cattle?
Authors: Voulgarakis Nikolaos , Gougoulis Dimitrios , Psalla Dimitra , Papakonstantinou Georgios , Katsoulos Panagiotis-Dimitrios , Katsoulis Konstantinos , Angelidou-Tsifida Mariana , Athanasiou Labrini , Papatsiros Vasilleios , Christodoulopoulos Georgios
Published: October 2023

Subacute ruminal acidosis (SARA) is one of the major nutritional disorders in the dairy and beef industries, leading to significant financial losses. Diagnosing SARA is challenging due to the need to evaluate multiple parameters, such as milk fat/protein ratio, ruminal lactate, and hemogram, instead of relying on a single definitive symptom or diagnostic method. This study aimed to evaluate the effectiveness of computerized rumen colorimetry in detecting SARA in beef cattle. Over one year, 75 cattle aged 8–10 months from five farms were periodically monitored for rumen pH prior to slaughter. Samples of rumen wall and rumen content were obtained at slaughter for analysis. The study found a positive correlation coefficient between rumen pH and color components, particularly for Red (0.853) and color lightness (L) (0.862). The darkening of the rumen epithelium’s color was attributed to the effect of rumen pH on the keratinized layer of the epithelium. Furthermore, an increase in the thickness of ruminal epithelium layers, particularly non-keratinized and total epithelium, was observed in animals with a history of SARA. It is possible that the lower rumen pH increases the rate of replacement of the keratinized epithelium, and the non-keratinized epithelium overgrows to compensate for the need to of produce keratinized layers. In conclusion, computerized rumen colorimetry shows promise as a reliable method for managing SARA in bovine farms by monitoring the condition in the slaughterhouse. Further research is needed to evaluate its effectiveness in detecting SARA in live animals.
Free and Interfacial Boundaries in Individual-Based Models of Multicellular Biological systems
Authors: Germano Domenic P. J. , Zanca Adriana , Johnston Stuart T. , Flegg Jennifer A. , Osborne James M.
Published: October 2023

Coordination of cell behaviour is key to a myriad of biological processes including tissue morphogenesis, wound healing, and tumour growth. As such, individual-based computational models, which explicitly describe inter-cellular interactions, are commonly used to model collective cell dynamics. However, when using individual-based models, it is unclear how descriptions of cell boundaries affect overall population dynamics. In order to investigate this we define three cell boundary descriptions of varying complexities for each of three widely used off-lattice individual-based models: overlapping spheres, Voronoi tessellation, and vertex models. We apply our models to multiple biological scenarios to investigate how cell boundary description can influence tissue-scale behaviour. We find that the Voronoi tessellation model is most sensitive to changes in the cell boundary description with basic models being inappropriate in many cases. The timescale of tissue evolution when using an overlapping spheres model is coupled to the boundary description. The vertex model is demonstrated to be the most stable to changes in boundary description, though still exhibits timescale sensitivity. When using individual-based computational models one should carefully consider how cell boundaries are defined. To inform future work, we provide an exploration of common individual-based models and cell boundary descriptions in frequently studied biological scenarios and discuss their benefits and disadvantages.
Insights on the Cesàro operator: shift semigroups and invariant subspaces
Authors: Gallardo-Gutiérrez Eva A. , Partington Jonathan R.
Published: October 2023

A closed subspace is invariant under the Cesàro operator $${\cal C}$$
C
on the classical Hardy space $${H^2}(\mathbb{D})$$

H
2

(
D
)
if and only if its orthogonal complement is invariant under the C0-semigroup of composition operators induced by the affine maps $${\varphi _t}(z) = {e^{ - t}}z + 1 - {e^{ - t}}$$

φ
t

(
z
)
=

e

−
t

z
+
1
−

e

−
t

for t ≥ 0 and $$z =\mathbb{D}$$
z
=
D
. The corresponding result also holds in the Hardy spaces Hp($$\mathbb{D}$$
D
) for 1 < p < ∞. Moreover, in the Hilbert space setting, by linking the invariant subspaces of $${\cal C}$$
C
to the lattice of the closed invariant subspaces of the standard right-shift semigroup acting on a particular weighted L2-space on the line, we exhibit a large class of non-trivial closed invariant subspaces and provide a complete characterization of the finite codimensional ones, establishing, in particular, the limits of such an approach towards describing the lattice of all invariant subspaces of $${\cal C}$$
C
. Finally, we present a functional calculus argument which allows us to extend a recent result by Mashreghi, Ptak and Ross regarding the square root of $${\cal C}$$
C
and discuss its invariant subspaces.
Removing lead from water with carboxylate dendrimers and magnetic nanoparticles modified with carboxylate dendrimers
Authors: Rincón-Montón David , Martínez-Salvador David , Sánchez-Nieves Javier , Gómez Rafael , de la Mata F. Javier , Cano Jesús
Published: October 2023

Contamination of water with heavy metals as lead (Pb2+) is a relevant problematic issue. In this work, we have tested different types of dendritic materials for lead removal from water and further recovery. The systems employed are magnetic nanoparticles (MNP) modified with monocarboxylate and dendritic carboxylate ligands, and they are compared to pristine MNP and carbosilane dendrimers. They are all effective at removing Pb2+, but the key variations are in their recyclability. The usage of a filtering membrane was required for dendrimers, which was significantly degraded by the acidic media. In terms of MNP, those that were covered by dendritic molecules were clearly less damaged in acidic media. Finally, isotherm analysis revealed that Pb2+ interacts differently with unmodified and modified MNP.
Assessment of genotoxicity, mutagenicity, and cytotoxicity of diclofenac and sulfamethoxazole at environmental concentrations on Vicia faba
Authors: Drzymała J. , Kalka J.
Published: October 2023

The contamination of the environment with pharmaceuticals and their residues has become a global issue. The main objective of study was to assess the genotoxicity, mutagenicity, and cytotoxicity of two drugs, diclofenac, sulfamethoxazole, and their binary mixture. The research focused on conducting a micronucleus assay using Vicia faba in water and soil environments. In the experiment, several parameters were monitored: mitotic index, presence of micronuclei, and chromosomal aberrations. The antioxidant enzymes activity in the plants leaves was measured. The concentrations of the drugs used in the analysis were representative of those currently detectable in the environment. The results indicated that diclofenac and sulfamethoxazole caused a reduction in the mitotic index by 45% and 47% in hydroponic, and 46% and 22% in soil cultures, respectively. Micronuclei and chromosomal aberrations were observed at the tested environmental concentrations (0.008–0.5 mg L−1). In the case of the drug mixture, the observed toxic effects in both cultivation were less significant than the predicted effects based on the Concentration Addition and Independent Action models. The tested compounds had an impact on the activity of enzymes. Even at environmental concentrations, the pharmaceuticals caused changes in catalase activity, with an average decrease of 39% in water and 10% in soil cultures, and in superoxide dismutase activity, showing an increase of 286% and 1835%, respectively. Overall, this study highlights the potential adverse effects of pharmaceutical contamination, even at low environmental concentrations. The findings underscore the importance of monitoring the presence of pharmaceutical residues to minimize their impact on ecosystems.