bluuebunny/crossref_metadata_2025 huggingface dataset:
Air pollution exposure during pregnancy and lung function in childhood: The LUIS study
Authors: Usemann Jakob , Mozun Rebeca , Kuehni Claudia E. , de Hoogh Kees , Flueckiger Benjamin , Singer Florian , Zwahlen Marcel , Moeller Alexander , Latzin Philipp ,   LUIS Study Group
Published: July 2024

Background

The adverse effects of high air pollution levels on childhood lung function are well‐known. Limited evidence exists on the effects of moderate exposure levels during early life on childhood lung function. We investigated the association of exposure to moderate air pollution during pregnancy, infancy, and preschool time with lung function at school age in a Swiss population‐based study.

Methods

Fine‐scale spatiotemporal model estimates of particulate matter with a diameter <2.5 µm (PM2.5) and nitrogen dioxide (NO2) were linked with residential address histories. We compared air pollution exposures within different time windows (whole pregnancy, first, second, and third trimester of pregnancy, first year of life, preschool age) with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) measured cross‐sectionally using linear regression models adjusted for potential confounders.

Results

We included 2182 children, ages 6−17 years. Prenatal air pollution exposure was associated with reduced lung function at school age. In children aged 12 years, per 10 µg·m−3 increase in PM2.5 during pregnancy, FEV1 was 55 mL lower (95% CI −84 to −25 mL) and FVC 62 mL lower (95% CI −96 to −28 mL). Associations were age‐dependent since they were stronger in younger and weaker in older children. PM2.5 exposure after birth was not associated with reduced lung function. There was no association between NO2 exposure and lung function.

Conclusion

In utero lung development is most sensitive to air pollution exposure, since even modest PM2.5 exposure during the prenatal time was associated with reduced lung function, most prominent in younger children.
Unveiling winter survival strategies: physiological and metabolic responses to cold stress of Monochamus saltuarius larvae during overwintering
Authors: Shi Fengming , Xing Yu , Niu Yiming , Cheng Ling , Xu Yabei , Li Xinyu , Ren Lili , Zong Shixiang , Tao Jing
Published: July 2024

BACKGROUND

Monochamus saltuarius is a destructive trunk‐borer of pine forest and an effective dispersal vector for pinewood nematode (PWN), a causative agent of pine wilt disease (PWD), which leads to major ecological disasters. Cold winter temperatures determine insect survival and distribution. However, little is known about the cold tolerance and potential physiological mechanisms of M. saltuarius.

RESULTS

We demonstrated that dead Pinus koraiensis trunks do not provide larvae with insulation. The M. saltuarius larvae are freeze‐tolerant species. Unlike most other freeze‐tolerant insects, they can actively freeze extracellular fluid at higher subzero temperatures by increasing their supercooling points. The main energy sources for larvae overwintering are glycogen and the mid‐late switch to lipid. The water balance showed a decrease in free and an increase in bound water of small magnitude. Cold stress promoted lipid peroxidation, thus activating the antioxidant system to prevent cold‐induced oxidative damage. We found eight main pathways linked to cold stress and 39 important metabolites, ten of which are cryoprotectants, including maltose, UDP‐glucose, d‐fructose 6P, galactinol, dulcitol, inositol, sorbitol, l‐methionine, sarcosine, and d‐proline. The M. saltuarius larvae engage in a dual respiration process involving both anaerobic and aerobic pathways when their bodily fluids freeze. Cysteine and methionine metabolism, as well as alanine, aspartate, and glutamate metabolism, are the most important pathways linked to antioxidation and energy production.

CONCLUSIONS

The implications of our findings may help strengthen and supplement the management strategies for monitoring, quarantine, and control of this pest, thereby contributing to controlling the further spread of PWD. © 2024 Society of Chemical Industry.
Light B Doping by Ion Implantation into High‐Purity Heteroepitaxial Diamond
Authors: Seki Yuhei , Yoshihara Minami , Kim Seong‐Woo , Koyama Koji , Hoshino Yasushi
Published: July 2024

The low‐concentration boron doping is performed from 1016 to 1018 cm−3 by ion implantation into heteroepitaxially synthesized large‐area diamond and electrical properties are investigated. Photoluminescence analysis is first carried out to clarify the optical properties of the heteroepitaxial diamond substrate. As a result, defect complexes of nitrogen‐vacancy and silicon‐vacancy are hardly detected in this substrate, suggesting that optically high‐purity diamond can be accomplished by heteroepitaxial growth. Then, the electrical properties of resistivity, mobility, carrier concentration, and conductive type by Hall effect measurements are investigated. For the samples with doping concentrations higher than 1016 cm−3, the electrical activation of implanted B acting as acceptors is confirmed. The compensation ratio for the sample with 3.5 × 1017 cm−3 concentration reaches 76%, indicating the presence of compensating donor‐like centers. With increasing the doping concentration to 3.5 × 1018 cm−3, the compensation ratio is significantly reduced to 35%. The observed mobility of the higher doped sample takes almost the ideal value observed for the sample doped by chemical vapor deposition process. It is suggested that the heteroepitaxial synthesis of large‐area and high‐purity substrates should contribute to the further development of the application to electronic, optical, and sensing devices in the future.
Investigation of the Impact of Crystalline Arsenolite Oxide Formations on Porous Gallium Arsenide
Authors: Suchikova Yana , Lysak Anastasiia , Kovachov Sergii , Konuhova Marina , Zhydachevskyy Yaroslav , Popov Anatoli I.
Published: July 2024

Herein, the impact of arsenolite oxide (As2O3) crystallites on the structural and optical properties of porous gallium arsenide (GaAs) is examined, focusing on understanding the potential passivation effect and its influence on material stability and safety. Utilizing a comprehensive set of analytical methods, including cathodoluminescence (CL) spectroscopy, Raman scattering spectroscopy, and X‐ray diffraction, the interaction between the GaAs substrate and arsenolite crystallites is characterized. The results indicate that the crystallites do not significantly alter the electronic and optical properties of the underlying GaAs, suggesting a possible passivating effect that could enhance device performance. However, concerns regarding arsenolite's environmental stability and toxicity prompt a cautious approach to its application. Herein, the need for further research into conditions conducive to natural oxide formation, exploration of alternative passivation strategies, and development of safe and stable oxide layers is underscored. Reproducible results are necessary to confirm the differences in CL signals between samples, as the current findings are based on single measurements.
Potency Assay Variability Estimation in Practice
Authors: Li Hang , Witkos Tomasz M. , Umlauf Scott , Thompson Christopher
Published: July 2024

During the drug development process, testing potency plays an important role in the quality assessment required for the manufacturing and marketing of biologics. Due to multiple operational and biological factors, higher variability is usually observed in bioassays compared with physicochemical methods. In this paper, we discuss different sources of bioassay variability and how this variability can be statistically estimated. In addition, we propose an algorithm to estimate the variability of reportable results associated with different numbers of runs and their corresponding OOS rates under a given specification. Numerical experiments are conducted on multiple assay formats to elucidate the empirical distribution of bioassay variability.
Developmental perturbation in human embryos: Clinical and biological significance learned from time‐lapse images
Authors: Ezoe Kenji , Takahashi Tsubasa , Miki Tetsuya , Kato Keiichi
Published: July 2024

Background

Time‐lapse technology (TLT) has gained widespread adoption worldwide. In addition to facilitating the undisturbed culture of embryos, TLT offers the unique capability of continuously monitoring embryos to detect spatiotemporal changes. Although these observed phenomena play a role in optimal embryo selection/deselection, the clinical advantages of introducing TLT remain unclear. However, manual annotation of embryo perturbation could facilitate a comprehensive assessment of developmental competence. This process requires a thorough understanding of embryo observation and the biological significance associated with developmental dogma and variation. This review elucidates the typical behavior and variation of each phenomenon, exploring their clinical significance and research perspectives.

Methods

The MEDLINE database was searched using PubMed for peer‐reviewed English‐language original articles concerning human embryo development.

Main findings

TLT allows the observation of consecutive changes in embryo morphology, serving as potential biomarkers for embryo assessment. In assisted reproductive technology laboratories, several phenomena have not revealed their mechanism, posing difficulties such as fertilization deficiency and morula arrest.

Conclusion

A profound understanding of the biological mechanisms and significance of each phenomenon is crucial. Further collaborative efforts between the clinical and molecular fields following translational studies are required to advance embryonic outcomes and assessment.
Very severe oligozoospermia with AZFc microdeletion patients may affect intracytoplasmic sperm injection clinical outcomes: A propensity score matching analysis
Authors: Zhang Huan , Li Huanzhu , Ma Shujuan , Zhang Shuoping , Li Wen , Gu Yifan , Zhang Erchen , Hu Liang
Published: July 2024

Purpose

To explore whether spermatozoa from AZFc microdeletion patients affect their outcomes of intracytoplasmic sperm injection (ICSI).

Methods

Eighty‐five patients with AZFc microdeletion were recruited. A control group of one hundred and forty patients with severe oligozoospermia but without AZF microdeletion was selected using propensity score matching analysis with a 1:2 nearest neighbor algorithm ratio. The ICSI outcomes of the two groups were compared.

Results

AZFc microdeletion had lower rates of normal fertilization (73% vs. 80%, p = 0.17) and high‐quality embryos (44% vs. 58%, p = 0.07) than the control group. There was no significant difference in the clinical pregnancy rate, miscarriage rate, and live birth rate between the two groups. When the sperm concentration was <1 million/mL, the AZFc microdeletion group exhibited lower rates of fertilization (71% vs. 80%, p = 0.03), high‐quality embryo (44% vs. 58%, p = 0.02), clinical pregnancy (57% vs. 76%, p = 0.02), and live birth (49% vs. 72%, p = 0.01) than the control group. However, if sperm concentration was ≥1 million/mL, no significant differences were found.

Conclusion

If the sperm concentration is <1 million/mL, AZFc microdeletion do have a detrimental effect on most outcomes of ICSI.
Liquid–Liquid Phase Separation Mediated Formation of Chiral 2D Crystalline Nanosheets of a Co‐Assembled System
Authors: Elizebath Drishya , Vedhanarayanan Balaraman , Raj Aparna , Sudarsanakumar C. , Lin Tsung‐Wu , Praveen Vakayil K.
Published: July 2024

The role of macromolecule‐macromolecule and macromolecule–H2O interactions and the resulting perturbation of the H‐bonded network of H2O in the liquid–liquid phase separation (LLPS) process of biopolymers are well‐known. However, the potential of the hydrated state of supramolecular structures (non‐covalent analogs of macromolecules) of synthetic molecules is not widely recognized for playing a similar role in the LLPS process. Herein, LLPS occurred during the co‐assembly of hydrated supramolecular vesicles (bolaamphiphile, BA1) with a net positive charge (zeta potential, ζ = +60 ± 2 mV) and a dianionic chiral molecule (disodium l‐[+]‐tartrate) is reported. As inferred from cryo‐transmission electron microscopy (TEM), the LLPS‐formed droplets serve as the nucleation precursors, dictating the structure and properties of the co‐assembly. The co‐assembled structure formed by LLPS effectively integrates the counter anion's asymmetry, resulting in the formation of ultrathin free‐standing, chiral 2D crystalline sheets. The significance of the hydrated state of supramolecular structures in influencing LLPS is unraveled through studies extended to a less hydrated supramolecular structure of a comparable system (BA2). The role of LLPS in modulating the hydrophobic interaction in water paves the way for the creation of advanced functional materials in an aqueous environment.
High‐Entropy Metal Nitride Embedded in Concave Porous Carbon Enabling Polysulfide Conversion in Lithium–Sulfur Batteries
Authors: Wang Ruirui , Jiao Jihuang , Liu Da , He Yufei , Yang Yaxiong , Sun Dalin , Pan Honge , Fang Fang , Wu Renbing
Published: July 2024

The practical implementation of lithium–sulfur batteries is severely hindered by the rapid capacity fading due to the solubility of the intermediate lithium polysulfides (LiPSs) and the sluggish redox kinetics. Herein, high‐entropy metal nitride nanocrystals (HEMN) embedded within nitrogen‐doped concave porous carbon (N‐CPC) polyhedra are rationally designed as a sulfur host via a facile zeolitic imidazolate framework (ZIF)‐driven adsorption‐nitridation process toward this challenge. The configuration of high‐entropy with incorporated metal manganese (Mn) and chromium (Cr) will optimize the d‐band center of active sites with more electrons occupied in antibonding orbitals, thus promoting the adsorption and catalytic conversion of LiPSs. While the concave porous carbon not only accommodates the volume change upon the cycling processes but also physically confines and exposes active sites for accelerated sulfur redox reactions. As a result, the resultant HEMN/N‐CPC composites‐based sulfur cathode can deliver a high specific capacity of 1274 mAh g−1 at 0.2 C and a low capacity decay rate of 0.044% after 1000 cycles at 1 C. Moreover, upon sulfur loading of 5.0 mg cm−2, the areal capacity of 5.0 mAh cm−2 can still be achieved. The present work may provide a new avenue for the design of high‐performance cathodes in Li–S batteries.
Comprehensive Understanding of Elemental Doping and Substitution of Ni‐Rich Cathode Materials for Lithium‐Ion Batteries via In Situ Operando Analyses
Authors: Byeon Yun Seong , Lee Wontae , Park Sangbin , Kim Dongil , Jung Jaewoo , Park Min‐Sik , Yoon Won‐Sub
Published: July 2024

This review explores the challenges and advancements in the development of high‐energy lithium‐ion batteries (LIBs), particularly focusing on the electrochemical and structural stability of Ni‐rich cathode materials. Despite their potential to increase the energy density of LIBs, these cathode materials encounter issues such as irreversible phase transitions and structural degradation during cycling, which ultimately affect their electrochemical performance. Elemental doping/substitution has emerged as promising strategies to address these challenges. However, the precise mechanisms underlying their performance enhancement remain unclear. The objective is to elucidate the complex reaction mechanisms triggered by doping and substitution in Ni‐rich cathode materials by employing in situ operando analyses to uncover their effects on electrochemical behavior and structural integrity during cycling. This comprehensive investigation aims to clarify the roles of elemental dopants or substituents in the crystal structures of Ni‐rich cathode materials, thereby offering valuable insights for the structural engineering of cathode materials in high‐energy LIBs. By elucidating these intricate mechanisms, this review provides a practical roadmap for future research and significantly contributes to LIB technology by guiding material design and optimization strategies in the development of advanced LIBs.
Dementia severity at incident diagnosis in a population representative sample of older Americans
Authors: Xu Shengjia , Fouladi‐Nashta Niloofar , Chen Yi , Zissimopoulos Julie
Published: July 2024

INTRODUCTION

We provide the first analysis of distribution of dementia severity at incident diagnosis for a population representative sample of older Americans.

METHODS

Using data from the Aging, Demographics, and Memory Study (ADAMS), the Health Retirement Study (HRS), and traditional Medicare claims, we estimated the Clinical Dementia Rating Scale for ADAMS respondents and applied parameter estimates to predict dementia severity for HRS respondents with claims‐based incident dementia diagnosis.

RESULTS

Seventy percent of older adults received a dementia diagnosis of mild cognitive impairment or mild dementia (early stages). Fewer individuals were diagnosed at early stages in years 2000 to 2008 (65%) compared to years 2009 to 2016 (76%). About 72% of non‐Hispanic white persons were diagnosed at early stages, compared to 63% non‐Hispanic black and 59% Hispanic persons. More males than females were diagnosed at early stages (75% vs 67%).

DISCUSSION

These data linkages allow population surveillance of early and equitable dementia detection in the older US population to assess clinical and policy levers to improve detection.

Highlights

For the US population 70 and older, 30% were diagnosed with dementia at a moderate or severe stage.

Fewer were diagnosed at early stages in years 2000 to 2008 compared to 2009 to 2016 (65% vs 76%).

A total of 72% of white persons were diagnosed at early stages, compared to 63% black and 59% Hispanic persons.

More males than females were diagnosed at early stages (75% vs 67%).

High wealth and education level were associated with diagnosis at early stages disease.
A Guide to Feature Importance Methods for Scientific Inference
Authors: Ewald Fiona Katharina , Bothmann Ludwig , Wright Marvin N. , Bischl Bernd , Casalicchio Giuseppe , König Gunnar
Published: July 2024

While machine learning (ML) models are increasingly used due to their high predictive power, their use in understanding the data-generating process (DGP) is limited. Understanding the DGP requires insights into feature-target associations, which many ML models cannot directly provide due to their opaque internal mechanisms. Feature importance (FI) methods provide useful insights into the DGP under certain conditions. Since the results of different FI methods have different interpretations, selecting the correct FI method for a concrete use case is crucial and still requires expert knowledge. This paper serves as a comprehensive guide to help understand the different interpretations of global FI methods. Through an extensive review of FI methods and providing new proofs regarding their interpretation, we facilitate a thorough understanding of these methods and formulate concrete recommendations for scientific inference. We conclude by discussing options for FI uncertainty estimation and point to directions for future research aiming at full statistical inference from black-box ML models.
CountARFactuals – Generating Plausible Model-Agnostic Counterfactual Explanations with Adversarial Random Forests
Authors: Dandl Susanne , Blesch Kristin , Freiesleben Timo , König Gunnar , Kapar Jan , Bischl Bernd , Wright Marvin N.
Published: July 2024

Counterfactual explanations elucidate algorithmic decisions by pointing to scenarios that would have led to an alternative, desired outcome. Giving insight into the model’s behavior, they hint users towards possible actions and give grounds for contesting decisions. As a crucial factor in achieving these goals, counterfactuals must be plausible, i.e., describing realistic alternative scenarios within the data manifold. This paper leverages a recently developed generative modeling technique – adversarial random forests (ARFs) – to efficiently generate plausible counterfactuals in a model-agnostic way. ARFs can serve as a plausibility measure or directly generate counterfactual explanations. Our ARF-based approach surpasses the limitations of existing methods that aim to generate plausible counterfactual explanations: It is easy to train and computationally highly efficient, handles continuous and categorical data naturally, and allows integrating additional desiderata such as sparsity in a straightforward manner.
D-terms in generalised complex geometry
Authors: Menet Vincent
Published: July 2024

Abstract

Generalised Complex Geometry provides a natural interpretation of the $$ \mathcal{N} $$
N
= 1 supersymmetry conditions for warped solutions of type II supergravity as differential equations on polyforms on the internal manifold. Written in this language the supersymmetry conditions correspond to calibration conditions for probe D-branes: D-string, domain-wall or space-filling branes, depending on the directions they span in the non-compact four-dimensional space. The BPS condition corresponding to the calibration of space-filling D-branes has been reformulated by Tomasiello, eliminating the explicit dependence on the metric. We generalise this derivation to the case of non-supersymmetric backgrounds violating the domain-wall and D-string calibration conditions. We use this reformulation to derive constraints that the ten-dimensional solutions with BPS space-filling sources must respect in order to dimensionally reduce to solutions of four-dimensional $$ \mathcal{N} $$
N
= 1 supergravity with non-vanishing F-terms and potentially non-vanishing D-terms. We give the equations of motion for the class of type II vacua satisfying these constraints in the language of pure spinors. We investigate how restrictive these constraints are for the class of type IIB SU(3) backgrounds with BPS space-filling O5-planes.
$$\varvec{S}$$-preclones and the Galois connection $$\varvec{{}^{S}{}\textrm{Pol}}$$–$$\varvec{{}^{S}{}\textrm{Inv}}$$, Part I
Authors: Jipsen Peter , Lehtonen Erkko , Pöschel Reinhard
Published: July 2024

We consider S-operations$$f :A^{n} \rightarrow A$$

f
:

A
n

→
A

in which each argument is assigned a signum$$s \in S$$

s
∈
S

representing a “property” such as being order-preserving or order-reversing with respect to a fixed partial order on A. The set S of such properties is assumed to have a monoid structure reflecting the behaviour of these properties under the composition of S-operations (e.g., order-reversing composed with order-reversing is order-preserving). The collection of all S-operations with prescribed properties for their signed arguments is not a clone (since it is not closed under arbitrary identification of arguments), but it is a preclone with special properties, which leads to the notion of S-preclone. We introduce S-relations$$\varrho = (\varrho _{s})_{s \in S}$$

ϱ
=

(

ϱ
s

)

s
∈
S

, S-relational clones, and a preservation property ("Equation missing"), and we consider the induced Galois connection $${}^{S}{}\textrm{Pol}$$

S

Pol

–$${}^{S}{}\textrm{Inv}$$

S

Inv

. The S-preclones and S-relational clones turn out to be exactly the closed sets of this Galois connection. We also establish some basic facts about the structure of the lattice of all S-preclones on A.
The Toxoplasma secreted effector TgWIP modulates dendritic cell motility by activating host tyrosine phosphatases Shp1 and Shp2
Authors: Morales Pavel , Brown Abbigale J. , Sangaré Lamba Omar , Yang Sheng , Kuihon Simon V.N.P. , Chen Baoyu , Saeij Jeroen P.J.
Published: July 2024

The obligate intracellular parasite Toxoplasma gondii causes life-threatening toxoplasmosis to immunocompromised individuals. The pathogenesis of Toxoplasma relies on its swift dissemination to the central nervous system through a ‘Trojan Horse’ mechanism using infected leukocytes as carriers. Previous work found TgWIP, a protein secreted from Toxoplasma, played a role in altering the actin cytoskeleton and promoting cell migration in infected dendritic cells (DCs). However, the mechanism behind these changes was unknown. Here, we report that TgWIP harbors two SH2-binding motifs that interact with tyrosine phosphatases Shp1 and Shp2, leading to phosphatase activation. DCs infected with Toxoplasma exhibited hypermigration, accompanying enhanced F-actin stress fibers and increased membrane protrusions such as filopodia and pseudopodia. By contrast, these phenotypes were abrogated in DCs infected with Toxoplasma expressing a mutant TgWIP lacking the SH2-binding motifs. We further demonstrated that the Rho-associated kinase (Rock) is involved in the induction of these phenotypes, in a TgWIP-Shp1/2 dependent manner. Collectively, the data uncover a molecular mechanism by which TgWIP modulates the migration dynamics of infected DCs in vitro.
In-depth Exploration of Temperature Trends in Morocco: Combining Traditional Methods of Mann Kendall with Innovative ITA and IPTA Approaches
Authors: Qadem Zohair , Tayfur Gokmen
Published: July 2024

This study examines trends in minimum and maximum temperatures at various climate stations located in different regions of Morocco for a period of five decades (1970 to 2019). Mann–Kendall, Sen’s estimator, Innovative Trend Analysis (ITA) and Innovative Polygon Trend Analysis (IPTA) were used in the analysis. The results show significant fluctuations, at different time scales, between minimum and maximum temperatures at all stations. In coastal areas, such as Rabat Sale, minimum temperatures fell during January and February while other months saw increases. Average minimum temperatures in Rabat Sale tend to fall by 0.5 °C. On the other hand, maximum temperatures in Rabat Sale rose by 0.2 °C. A decrease of 0.4 °C for Tmin and 1.6 °C for Tmax were observed in higher continental regions, such as Meknes. Other stations, such as Fez Sais (0.6 °C Tmin and 2.6 °C Tmax) and Taza (1.1 °C Tmin and 2.6 °C Tmax) showed an upward trend. Trends also vary, with notable increases in minimum and maximum temperatures, indicating different climatic dynamics according to altitude and locality. In particular, the ITA highlights a significant increase in annual maximum temperatures, with a P-value < 0.05 and trend slopes ranging from 0.0015 °C per year in Rabat Sale to 0.0076 °C per year in Taza. In addition, the IPTA results confirm diversity of upward and downward trends on monthly and seasonal scales, highlighting impact of geographical factors such as proximity to sea, topography, and continentality that contribute to formation of regional microclimates. The results highlight significant impact of climate change in Morocco.
Zero-cycles in families of rationally connected varieties
Authors: Lüders Morten
Published: July 2024

We study zero-cycles in families of rationally connected varieties. We show that for a smooth projective scheme over a henselian discrete valuation ring the restriction of relative zero cycles to the special fiber induces an isomorphism on Chow groups if the special fiber is separably rationally connected. We further extend this result to certain higher Chow groups and develop conjectures in the non-smooth case. Our main results generalise a result of Kollár (Publ. Res. Inst. Math. Sci. 40(3):689–708, 2004).
Effects of anesthesia with sevoflurane on outcome parameters in murine experimental studies
Authors: Wrba Jonas C. , Lupu Ludmila , Braumüller Sonja , Neff Thomas A. , Halbgebauer Rebecca , Palmer Annette , Huber-Lang Markus
Published: July 2024

Purpose

Multiple murine studies modelling the immuno-pathophysiological consequences of trauma, shock, burn or sepsis were performed during the last decades. Almost every animal model requires anesthesia for practical and ethical reasons. Furthermore, often, corresponding control groups involve untreated animals without or with a limited exposure to anesthetics. However, the influences of anesthetic drugs on immuno-pathophysiological reactions remain insufficiently investigated. Therefore, we aimed to closer characterize the anesthetic impact exemplified by sevoflurane on the organ performance in mice and thereby investigate the influence of anesthesia itself on major outcome parameters in animal studies.

Methods

C57/BL6 mice were subjected either to 270 min of sevoflurane narcosis or directly euthanized. Plasma, BAL-fluids, lungs, kidneys, liver and intestine were collected and examined for immunological, functional and morphological changes.

Results

Systemic levels of the cytokine keratinocyte chemoattractant (KC) were raised in the narcosis group, while concentrations of high mobility group box protein 1 (HMGB-1) as a major inflammatory marker were reduced. In the lungs, levels of HMGB-1 and interleukin 6 (IL-6) were reduced. In contrast, systemic concentrations of intestinal fatty acid binding-protein (i-FABP) as an intestinal damage marker were elevated. Furthermore, liver-type fatty acid binding-protein (L-FABP) levels were lower in the narcosis animals, and inflammatory markers were reduced in liver tissues. Anesthesia also ameliorated the inflammatory reaction in renal tissues, while plasma levels of urea and creatinine were elevated, reflecting either dehydration and/or impaired renal function.

Conclusion

As anesthesia with sevoflurane exhibited distinct effects in different organs, it is difficult to predict its specific impact on targets of interest in in vivo studies. Therefore, further studies are required to clarify the effects of different anesthetic drugs. Overall, the inclusion of a control group subjected to the same anesthesia protocol as the experimental groups of interest seems helpful to precisely define the inherent impact of the anesthetic when investigating immuno-pathophysiologic conditions in vivo.
Intolerance of uncertainty and psychological flexibility as predictors of mental health from adolescence to old age
Authors: Okayama Sakiko , Minihan Savannah , Andrews Jack L. , Daniels Sarah , Grunewald Karina , Richards Matthew , Wang Weike , Hasan Yasmin , Schweizer Susanne
Published: July 2024

Purpose

The COVID-19 pandemic brought with it significant social, economic and health uncertainties. These were proposed to impact young people more compared to adults, leading adolescents to report more mental health problems during the pandemic. The current study examined whether differences in cognitive risk (tolerance of uncertainty) and protective (psychological flexibility) factors accounted for age-related differences in depression and anxiety.

Methods

These associations were investigated in the COVID-19 Risks Across the Lifespan (CORAL) cohort (N = 2280, 11–89 years).

Results

The results showed that adolescents experienced greater intolerance of uncertainty and lower psychological flexibility compared to adults and older adults. Tolerance of uncertainty did not account for age-related differences in depression or anxiety. However, psychological flexibility conferred more protective advantage for anxiety in adults compared to adolescents.

Conclusion

The observed age-related differences in risk and protective factors advance our understanding of developmental vulnerabilities to depression and anxiety. Implications for mental health interventions in the context of future pandemics are discussed.
The impacts of non-perceptual cognition (NPC) on design process and ideation
Authors: Lee Ju Hyun , Ostwald Michael J.
Published: July 2024

Past research theorises that eye-closure and associated mental visualisation, which occurs during the design process, may be important for supporting creativity. Despite these claims, little empirical evidence is available about the results of mental recall in design. In response to this knowledge gap, this research reports the results of a protocol analysis of 35 designers’ creative processes, to examine the impacts of non-perceptual cognition (NPC) on design process and ideation. The results suggest that NCP events facilitate idea generation in the individual design process, confirming that ‘seeing with the mind’s eyes’ is an important process in designing. The research concludes with a discussion about the implications of the findings and its contribution to research into design and creativity.
Age-specific composition of milk microbiota in Tibetan sheep and goats
Authors: Cao Xi , Fang Yumeng , Bandan Pingcuo , Suo Langda , Jiacuo Gesang , Wu Yujiang , Cuoji Awang , Zhuoga Deqing , Chen Yulin , Ji De , Quzhen Ciren , Zhang Ke
Published: July 2024

This study investigates the dynamic changes in milk nutritional composition and microbial communities in Tibetan sheep and goats during the first 56 days of lactation. Milk samples were systematically collected at five time points (D0, D7, D14, D28, D56) post-delivery. In Tibetan sheep, milk fat, protein, and casein contents were highest on D0, gradually decreased, and stabilized after D14, while lactose and galactose levels showed the opposite trend. Goat milk exhibited similar initial peaks, with significant changes particularly between D0, D7, D14, and D56. 16S rRNA gene sequencing revealed increasing microbial diversity in both species over the lactation period. Principal coordinates analysis identified distinct microbial clusters corresponding to early (D0–D7), transitional (D14–D28), and mature (D56) stages. Core phyla, including Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, dominated the milk microbiota, with significant temporal shifts. Core microbes like Lactobacillus, Leuconostoc, and Streptococcus were common in both species, with species-specific taxa observed (e.g., Pediococcus in sheep, Shewanella in goats). Furthermore, we observed a highly shared core microbiota in sheep and goat milk, including Lactobacillus, Leuconostoc, and Streptococcus. Spearman correlation analysis highlighted significant relationships between specific microbial genera and milk nutrients. For instance, Lactobacillus positively correlated with total solids, non-fat milk solids, protein, and casein, while Mannheimia negatively correlated with protein content. This study underscores the complex interplay between milk composition and microbial dynamics in Tibetan sheep and goats, informing strategies for livestock management and nutritional enhancement.

Key points

• The milk can be classified into three types based on the microbiota composition

• The changes of milk microbiota are closely related to the variations in nutrition

• Filter out microbiota with species specificity and age specificity in the milk
Diagnostic accuracy of the Clear Cell Likelihood Score and selected MRI parameters in the characterization of indeterminate renal masses – a single-institution study
Authors: Blachura Tomasz , Matusik Patrycja S. , Kowal Aleksander , Radzikowska Julia , Jarczewski Jarosław D. , Skiba Łukasz , Popiela Tadeusz J. , Chrzan Robert
Published: July 2024

Purpose

We aimed to assess the diagnostic accuracy of the clear cell likelihood score (ccLS) and value of other selected magnetic resonance imaging (MRI) features in the characterization of indeterminate small renal masses (SRMs).

Methods

Fifty patients with indeterminate SRMs discovered on MRI between 2012 and 2023 were included. The ccLS for the characterization of clear cell renal cell carcinoma (ccRCC) was calculated and compared to the final diagnosis (ccRCC vs. ‘all other’ masses).

Results

The ccLS = 5 had a satisfactory accuracy of 64.0% and a very high specificity of 96.3%; however, its sensitivity of 26.1% was relatively low. Receiver operating curve (ROC) analysis revealed that from the selected MRI features, only T1 ratio and arterial to delayed enhancement (ADER) were good discriminators between ccRCC and other types of renal masses (area under curve, AUC = 0.707, p = 0.01; AUC = 0.673, p = 0.03; respectively). The cut-off points determined in ROC analysis using the Youden index were 0.73 (p = 0.01) for T1 ratio and 0.99 for ADER (p = 0.03). The logistic regression model demonstrated that ccLS = 5 and T1 ratio (OR = 15.5 [1.1-218.72], p = 0.04; OR = 0.002 [0.00-0.81], p = 0.04) were significant predictors of ccRCC.

Conclusions

The ccLS algorithm offers an encouraging method for the standardization of imaging protocols to aid in the diagnosis and management of SRMs in daily clinical practice by enhancing detectability of ccRCC and reducing the number of unnecessary invasive procedures for benign or indolent lesions. However, its diagnostic performance needs multi-center large cohort studies to validate it before it can be incorporated as a diagnostic algorithm and will guide future iterations of clinical guidelines. The retrospective nature of our study and small patient population confined to a single clinical center may impact the generalizability of the results; thus, future studies are required to define whether employment of the T1 ratio or ADER parameter may strengthen the diagnostic accuracy of ccRCC diagnosis.

Graphical Abstract
Patient Weight and Chemoprophylaxis in Abdominoplasty: Does It Result in More Bleeding Events?
Authors: Ibrahim Ahmed , Steinvall Ingrid , Elawa Sherif , Ellabban Mohamed A. , Mohamed Mostafa K. , Elmasry Moustafa , Abdelrahman Islam
Published: July 2024

Background

Bariatric surgery has gained popularity in recent decades as an effective treatment for obesity. Abdominoplasty is one of the most often performed aesthetic procedures all over the world. In post-bariatric patients undergoing abdominoplasty, the diameter size and number of the abdominal wall perforators increase proportionally with increased body weight. Postoperative complications that may occur are haematoma, and venous thromboembolism (VTE). In plastic surgery procedures VTE prophylaxis grades vary due to the lack of consensus and clear guidelines. The aim of this study was to explore the frequency of postoperative bleeding and VTE in patients undergoing abdominoplasty and to explore the risk factors associated with major bleeding.

Methods

A retrospective single-centre study of adult patients who were operated on by abdominoplasty between 2011 and 2020. Chemoprophylaxis including low molecular weight heparin (LMHW) was recommended when the operating time exceeded 2 h.

Results

A total of 102 patients were included. There were no patients with VTE. Eight patients were re-operated for major haematoma. The weight loss (peak weight to weight before the abdominoplasty) was 14.4 kg larger in the re-operation group (p = 0.03). Eighty-eight percent in the re-operation group and 67% in the other group were treated with LMWH (p = 0.43). Multivariable logistic regression showed that with each decrease from the peak in BMI kg/m2 the risk of re-operation for major haematoma was increased by 22% (p = 0.02).

Conclusion

Abdominoplasty in patients after massive weight loss has a higher risk of postoperative bleeding. Having a clear protocol for chemoprophylaxis should be considered.

Level of Evidence III

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Comprehensive meta-analysis of surgical procedure for congenital diaphragmatic hernia: thoracoscopic versus open repair
Authors: Shibuya Soichi , Paraboschi Irene , Giuliani Stefano , Tsukui Takafumi , Matei Andreea , Olivos Maricarmen , Inoue Mikihiro , Clarke Simon A. , Yamataka Atsuyuki , Zani Augusto , Eaton Simon , De Coppi Paolo
Published: July 2024

Purpose

Previous studies have shown a higher recurrence rate and longer operative times for thoracoscopic repair (TR) of congenital diaphragmatic hernia (CDH) compared to open repair (OR). An updated meta-analysis was conducted to re-evaluate the surgical outcomes of TR.

Methods

A comprehensive literature search comparing TR and OR in neonates was performed in accordance with the PRISMA statement (PROSPERO: CRD42020166588).

Results

Fourteen studies were selected for quantitative analysis, including a total of 709 patients (TR: 308 cases, OR: 401 cases). The recurrence rate was higher [Odds ratio: 4.03, 95% CI (2.21, 7.36), p < 0.001] and operative times (minutes) were longer [Mean Difference (MD): 43.96, 95% CI (24.70, 63.22), p < 0.001] for TR compared to OR. A significant reduction in the occurrence of postoperative bowel obstruction was observed in TR (5.0%) compared to OR (14.8%) [Odds ratio: 0.42, 95% CI (0.20, 0.89), p = 0.02].

Conclusions

TR remains associated with higher recurrence rates and longer operative times. However, the reduced risk of postoperative bowel obstruction suggests potential long-term benefits. This study emphasizes the importance of meticulous patient selection for TR to mitigate detrimental effects on patients with severe disease.
Ulcerative colitis in a transgender woman with a sigmoid neovagina: a case report
Authors: Sadeghi Anahita , Bahrami Hezaveh Ehsan , Ali Asgari Ali
Published: July 2024

Background

Sex reassignment surgery (SRS) is a necessary step in transitioning into the desired gender for male-to-female transgender individuals. This study focuses on a rare complication developed following SRS, aiming to highlight potential complications associated with this procedure.

Case presentation

This report describes a 49-year-old transgender woman with a history of SRS who developed bloody diarrhea and neovaginal bleeding 10 years later. A colonoscopy revealed features compatible with ulcerative colitis, which was confirmed by a biopsy.

Conclusions

The unpredictable clinical course of this phenomenon may prompt surgeons to reconsider the use of a rectosigmoid colon to create a neovagina. This case report underscores the necessity of long-term monitoring for gastrointestinal complications in transgender women post-SRS when a rectosigmoid colon segment is utilized for neovaginal construction.
Can geroscience be translated into healthcare?
Authors: Ferrucci Luigi , Tanaka Toshiko , Polidori M. Cristina
Published: July 2024

As an introduction to this special issue on geroscience, the present work focuses on the complexity of disentangling biomolecular mechanisms of aging from biopsychosocial causes of accelerated aging. Due to this complexity, the biomolecular aging hallmarks of frailty and multimorbidity as predominant aging phenotypes in geriatrics reflect single aspects of the aging process. A possible approach to facilitate the integration of geroscience into healthcare might be to consider aging as the dynamic ratio between damage accumulation at the molecular and cellular level and resilience as strategies that prevent or repair such damage. There is a large body of evidence to show that geroscience has the potential to change healthcare; however, reaching a consensus and translating the best tool to measure aging needs more research on 1) the sensitivity of biomarkers to interventions and 2) the relationship between changes in biomarkers and changes in health trajectories.
Identification of retinal oligomeric, citrullinated, and other tau isoforms in early and advanced AD and relations to disease status
Authors: Shi Haoshen , Mirzaei Nazanin , Koronyo Yosef , Davis Miyah R. , Robinson Edward , Braun Gila M. , Jallow Ousman , Rentsendorj Altan , Ramanujan V. Krishnan , Fert-Bober Justyna , Kramerov Andrei A. , Ljubimov Alexander V. , Schneider Lon S. , Tourtellotte Warren G. , Hawes Debra , Schneider Julie A. , Black Keith L. , Kayed Rakez , Selenica Maj-Linda B. , Lee Daniel C. , Fuchs Dieu-Trang , Koronyo-Hamaoui Maya
Published: July 2024

This study investigates various pathological tau isoforms in the retina of individuals with early and advanced Alzheimer’s disease (AD), exploring their connection with disease status. Retinal cross-sections from predefined superior-temporal and inferior-temporal subregions and corresponding brains from neuropathologically confirmed AD patients with a clinical diagnosis of either mild cognitive impairment (MCI) or dementia (n = 45) were compared with retinas from age- and sex-matched individuals with normal cognition (n = 30) and non-AD dementia (n = 4). Retinal tau isoforms, including tau tangles, paired helical filament of tau (PHF-tau), oligomeric-tau (Oligo-tau), hyperphosphorylated-tau (p-tau), and citrullinated-tau (Cit-tau), were stereologically analyzed by immunohistochemistry and Nanostring GeoMx digital spatial profiling, and correlated with clinical and neuropathological outcomes. Our data indicated significant increases in various AD-related pretangle tau isoforms, especially p-tau (AT8, 2.9-fold, pS396-tau, 2.6-fold), Cit-tau at arginine residue 209 (CitR209-tau; 4.1-fold), and Oligo-tau (T22+, 9.2-fold), as well as pretangle and mature tau tangle forms like MC-1-positive (1.8-fold) and PHF-tau (2.3-fold), in AD compared to control retinas. MCI retinas also exhibited substantial increases in Oligo-tau (5.2-fold), CitR209-tau (3.5-fold), and pS396-tau (2.2-fold). Nanostring GeoMx analysis confirmed elevated retinal p-tau at epitopes: Ser214 (2.3-fold), Ser396 (2.6-fold), Ser404 (2.4-fold), and Thr231 (1.8-fold), particularly in MCI patients. Strong associations were found between retinal tau isoforms versus brain pathology and cognitive status: a) retinal Oligo-tau vs. Braak stage, neurofibrillary tangles (NFTs), and CDR cognitive scores (ρ = 0.63–0.71), b) retinal PHF-tau vs. neuropil threads (NTs) and ABC scores (ρ = 0.69–0.71), and c) retinal pS396-tau vs. NTs, NFTs, and ABC scores (ρ = 0.67–0.74). Notably, retinal Oligo-tau strongly correlated with retinal Aβ42 and arterial Aβ40 forms (r = 0.76–0.86). Overall, this study identifies and quantifies diverse retinal tau isoforms in MCI and AD patients, underscoring their link to brain pathology and cognition. These findings advocate for further exploration of retinal tauopathy biomarkers to facilitate AD detection and monitoring via noninvasive retinal imaging.