bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mu‐opioid receptors in tachykinin‐1‐positive cells mediate the respiratory and antinociceptive effects of the opioid fentanyl
Authors: Furdui Andreea , da Silveira Scarpellini Carolina , Montandon Gaspard 
Published: November 2024

AbstractBackground and PurposeOpioid drugs are potent analgesics that carry the risk of respiratory side effects due to actions on μ‐opioid receptors (MORs) in brainstem regions that control respiration. Substance P is encoded by the Tac1 gene and is expressed in neurons regulating breathing, nociception, and locomotion. Tac1‐positive cells also express MORs in brainstem regions mediating opioid‐induced respiratory depression. We determined the role of Tac1‐positive cells in mediating the respiratory effects of opioid drugs.Experimental ApproachIn situ hybridization was used to determine Oprm1 mRNA expression (gene encoding MORs) in Tac1‐positive cells in regions regulating respiratory depression by opioid drugs. Conditional knockout mice lacking functional MORs in Tac1‐positive cells were produced and the respiratory and locomotor responses to the opioid analgesic fentanyl were assessed using whole‐body plethysmography. A tail immersion assay was used to assess the antinociceptive response to fentanyl.Key ResultsOprm1 mRNA was highly expressed (>80%) in subpopulations of Tac1‐positive cells in the preBötzinger Complex, nucleus tractus solitarius, and Kölliker–Fuse/lateral parabrachial region. Conditionally knocking out MORs in Tac1‐positive cells abolished the effects of fentanyl on respiratory rate, relative tidal volume, and relative minute ventilation compared with control mice. Importantly, the antinociceptive response of fentanyl was eliminated in mice lacking functional MORs in Tac1‐positive cells, whereas locomotor effects induced by fentanyl were preserved.Conclusions and ImplicationsOur findings suggest that Tac1‐positive cells mediate the respiratory depressive and antinociceptive effects of the opioid fentanyl, providing important insights for the development of pain therapies with reduced risk of respiratory side effects.
Orexin‐A Attenuates the Inflammatory Response in Sepsis‐Associated Encephalopathy by Modulating Oxidative Stress and Inhibiting the ERK/NF‐κB Signaling Pathway in Microglia and Astrocytes
Authors: Guo Jing , Kong Dexun , Luo Junchi , Xiong Tao , Wang Fang , Deng Mei , Kong Zhuo , Yang Sha , Da Jingjing , Chen Chaofei , Lan Jinhai , Chu Liangzhao , Han Guoqiang , Liu Jian , Tan Ying , Zhang Jiqin 
Published: November 2024

ABSTRACTBackgroundOxidative stress‐induced inflammation is a major pathogenic mechanism in sepsis‐associated encephalopathy (SAE). We hypothesized that regulation of reactive oxygen species (ROS) by the neuropeptide orexin‐A could prevent SAE‐induced oxidative stress and inflammation. Therefore, the aim of this study was to investigate the effects of orexin‐A on oxidative stress and inflammation in SAE in mice.MethodsAdult male mice were treated with orexin‐A (250 μg/kg, intranasal administration) to establish a cecal ligation perforation (CLP) model. We performed behavioral tests, observed neuronal damage in the hippocampal region, measured the levels of ROS, NOX2, and observed the structure of mitochondria by transmission electron microscopy. We then examined the inflammatory factors TNF‐α and IL‐1β, the activation of microglia and astrocytes, the expression of ERK/NF‐κB, C3, and S100A10, and the presence of A1 type astrocytes and A2 type astrocytes.ResultsOrexin‐A treatment improved cognitive performance in CLP‐induced SAE mice, attenuated neuronal apoptosis in the hippocampal region, ameliorated ROS levels and the extent of mitochondrial damage, and reduced protein expression of NOX2 in hippocampal tissue. In addition, orexin‐A treatment significantly reduced microglia and astrocyte activation, inhibited the levels of P‐ERK and NF‐κB, and reduced the release of IL‐1β and TNF‐α, which were significantly increased after CLP. Finally, Orexin‐A treatment significantly decreased the number of C3/glial fibrillary acidic protein (GFAP)‐positive cells and increased the number of S100A10/GFAP‐positive cells.ConclusionOur data suggest that orexin‐A reduces ROS expression by inhibiting CLP‐induced NOX2 production, thereby attenuating mitochondrial damage and neuronal apoptosis. Its inhibition of microglial and A1‐type astrocyte activation and inflammation was associated with the ERK/NF‐κB pathway. These suggest that orexin‐A may reduce cognitive impairment in SAE by reducing oxidative stress‐induced inflammation.
Prevention and Treatment of Alzheimer's Disease Via the Regulation of the Gut Microbiota With Traditional Chinese Medicine
Authors: Long Jinyao , Zhang Jiani , Zeng Xin , Wang Min , Wang Ningqun 
Published: November 2024

ABSTRACTAlzheimer's disease (AD) is caused by a variety of factors, and one of the most important factors is gut microbiota dysbiosis. An imbalance in the gut mincrobiota have been shown to change the concentrations of lipopolysaccharide and short‐chain fatty acids. These microorganisms synthesize substances that can influence the levels of a variety of metabolites and cause multiple diseases through the immune response, fatty acid metabolism, and amino acid metabolism pathways. Furthermore, these metabolic changes promote the formation of β‐amyloid plaques and neurofibrillary tangles. Thus, the microbiota–gut–brain axis plays an important role in AD development. In addition to traditional therapeutic drugs such as donepezil and memantine, traditional Chinese medicines (TCMs) have also showed to significantly decrease the severity of AD symptoms and suppress the underlying related mechanisms. We searched for studies on the effects of different herbal monomers, single herbs, and polyherbal formulas on the gut microbiota of AD patients and identified the relevant pathways through which the gut microbiota affected AD. We conclude that improvements in the gut microbiota not only decrease the occurrence of inflammatory reactions but also reduce the deposition of central pathological products. Herbal monomers have a stronger effect on improving of central pathology. Polyherbal formulas have the most extensive effect on the gut microbiota in patients with AD. Among the effects of formulas, the anti‐inflammatory effect is the most essential and is also the main concern regarding the use of TCMs in treating AD from the viewpoint of the gut microbiota. We hope that this review will be helpful for providing new ideas for the clinical application of TCMs in the treatment of AD.
Histopathologic Comparisons of Discoid Lupus Erythematosus and Folliculotropic Mycosis Fungoides in a Series of 43 Cases
Authors: Cascardo Camilla A. , Mansour Meghan R. , Oska Sandra , Sundram Uma 
Published: November 2024

ABSTRACTBackgroundFolliculotropic mycosis fungoides (FMF) is a rare cutaneous malignancy that can be mistaken for inflammatory diseases, such as discoid lupus erythematosus (DLE), due to the variability of histopathological findings.MethodsThis study aims to provide dermatopathologists with evidence‐based histopathologic criteria to distinguish DLE from FMF by reporting overlapping and distinguishing microscopic features. Forty‐three biopsies from patients with a confirmed diagnosis of DLE or FMF were graded for the presence or absence of 18 histopathologic features.ResultsThe main histopathologic findings present in nearly all DLE and FMF biopsies were folliculocentric and folliculotropic patterns. Comedones, granulomas, and folliculitis were not prominent. Follicular hyperplasia, follicular plugging, interstitial mucin, lichenoid/interface dermatitis, and plasma cells were significantly more common in DLE biopsies, while follicular mucinosis and eosinophils were significantly more common in FMF samples. Cytologic atypia ranged from none to mild in DLE and mild to moderate in FMF. Rarely, both sets of biopsies contained epidermotropism, spongiosis, or peri‐eccrine infiltration.ConclusionWhile many histopathological features present in DLE overlap with features found in FMF, such as folliculocentrism and folliculotropism, significant differences do exist. Therefore, when diagnosing FMF, it is important to follow established criteria that differentiate this malignancy from inflammatory conditions such as DLE.
S3‐Leitlinie: Diagnostik und Therapie der epidermalen Nekrolyse (Stevens‐Johnson‐Syndrom und toxisch epidermale Nekrolyse) – Teil 2: Supportive Therapie von EN im akuten und postakuten Stadium
Authors: Paulmann Maren , Heuer Ruben , Annecke Thorsten , Behr Björn , Boch Katharina , Boos Anja M. , Brockow Knut , French Lars E. , Gille Jochen , Gundlach Verena , Hartmann Bernd , Höger Peter , Hofmann Silke C. , Klein Tobias , Lehnhardt Marcus , Liß Yvonne , Maier Philip , Mandel Philipp , Marathovouniotis Nicos , Marlok Finnja , Mittelviefhaus Hans , Pleyer Uwe , Pradeau Marie , Rall Katharina , Rieg Siegbert , Rittner Heike , Sander Frank , Schnitzler Stefan , Schut Christina , Stolle Annette , Vorobyev Artem , Wedi Bettina , Weiss Johannes , Zepp Maximilian , Ziemer Mirjana , Mockenhaupt Maja , Nast Alexander 
Published: November 2024

ZusammenfassungStevens‐Johnson‐Syndrom und toxisch epidermale Nekrolyse (SJS/TEN) sind seltene, in erster Linie arzneimittelinduzierte, akut lebensbedrohliche Erkrankungen der Haut und Schleimhäute. SJS und TEN werden heute als Varianten einer Krankheitsentität mit unterschiedlichem Schweregrad betrachtet, die als epidermale Nekrolyse (EN) bezeichnet wird. Die epidermale Nekrolyse geht mit hoher Morbidität und Letalität einher und stellt eine große Krankheitslast für die Betroffenen dar. Die Leitlinie „Diagnostik und Therapie der epidermalen Nekrolyse (Stevens‐Johnson‐Syndrom und toxisch epidermale Nekrolyse)“ wurde unter systematischer Berücksichtigung bestehender wissenschaftlicher Literatur und im formalen Konsensusverfahren nach dem Regelwerk der AWMF entwickelt, um klinische Entscheidungsfindungen evidenzbasiert zu unterstützen. Die interdisziplinäre Leitlinienkommission bestand aus Vertretern verschiedener Fachgesellschaften sowie aus Patientenvertretern. Die Leitlinie richtet sich an Ärzte der Fachgebiete Dermatologie, Ophthalmologie, plastische Chirurgie, Intensivmedizin sowie Kinder‐ und Jugendmedizin in Klinik und Praxis sowie an andere medizinische Fachgebiete, die an der Diagnostik und Behandlung von EN beteiligt sind. Zusätzlich richtet sich die Leitlinie an Patienten, deren Angehörige, Kostenträger und politische Entscheidungsträger. Dieser zweite Teil behandelt die Themen der supportiven Therapie in der Akutphase von EN und die ambulante Weiterbehandlung.
How Do Species Traits and Biogeographical Factors Determine the Fate of Amphibians After Long‐Term Fragmentation?
Authors: Chen Chuanwu , Zhan Chengxiu , Foufopoulos Johannes , Wang Yanping 
Published: November 2024

ABSTRACTAimIdentifying key factors that render certain species more vulnerable to fragmentation is vital for elucidating processes underlying extinction and targeting conservation priorities. However, few studies have explored the delayed ecological responses of species following isolation. To bridge the gap, we conducted comprehensive analyses of correlates of extinction vulnerability and biogeographical variation in amphibians over long‐term fragmentation.LocationZhoushan Archipelago, China.MethodsWe sampled the occupancy of amphibians on 37 land‐bridge islands. We calculated three metrics of extinction vulnerability (population extinction rate, island occupancy frequency and species nestedness ranking) for each species and correlated these variables with eight species' traits. We further explored biogeographical variations in amphibians by relating five biogeographical variables to species' probability of occurrence and calculated the threshold for the persistence of each species on islands.ResultsSpecies with low natural abundance, larger egg sizes, smaller clutch sizes or restricted geographical distributions were more likely to experience higher population extinction rates and species nestedness rankings, while lower island occupancy frequencies across islands. Although most species were found on larger islands, we observed significant increases in the occurrence probabilities with island area for five species. The estimated areas with a 50% chance of occurrence ranged from 0.39 to 199.5 km2. Interestingly, the likelihood of occurrence of Hyla chinensis (treefrog) was negatively related to distance to the mainland after controlling for the effect of area.Main ConclusionsOur study highlights the variation in the fragmentation sensitivity of amphibians. Species distribution was primarily regulated by area‐related extinction, particularly for those with ‘slow’ life history strategies or restricted ranges. Overall, management efforts should focus on species with extinction‐prone traits and landscape features that threaten the persistence of populations. Future studies should consider the sequential separation of island populations and the interaction of traits to reveal the fate of species to fragmentation.
Clinical Efficacy of CBCT and 3D‐Printed Replicas in Molar Autotransplantation: A Controlled Clinical Trial
Authors: Lejnieks Miks , Akota Ilze , Jākobsone Gundega , Neimane Laura , Uribe Sergio E. 
Published: November 2024

ABSTRACTBackground/AimTo evaluate the efficacy of the combined cone‐beam (CBCT)/3D‐replicas protocol on the clinical and radiographic outcomes of autotransplanted molars.Material and MethodsControlled clinical trial registered ISRCTN13563091 from August 2019 to September 2022. Patients aged 13–22 years requiring permanent premolar extraction and having at least one non‐erupted third molar were enrolled at the Institute of Stomatology, Stradins University, Riga, Latvia. Patients in the 3D‐replicas (n = 30) underwent maxillary CBCT scans and had 3D‐printed replicas of the third molar fabricated, while the control group (n = 28) did not. The clinical outcomes included tooth mobility, bleeding on probing, and periodontal pocket depth assessed at 3, 6, and 12 months. The radiographic outcomes included root development, obliteration, periapical status, and crown changes at 12 months.ResultsOf the 55 patients assigned to interventions, 46 completed the study. No significant differences in survival and radiographic outcomes were found between the control (n = 22) and 3D‐replica group (n = 24): root development (p = 0.3), root resorption (p = 0.057), periapical status (p = 0.7), and crown/root ratio change (p = 0.4). Logistic regression showed no significant associations between radiologic predictors (root resorption: p = 0.4; periapical status: p > 0.9; root development: p = 0.8). Significant clinical outcome predictors included total operative time (β = 0.0043, p = 0.049), Moorrees' stage (stage 4: β = −0.31, p < 0.001; stage 5: β = −0.39, p < 0.001), and four donor placement times (β = 0.93, p < 0.001), but group assignment was not a significant predictor.ConclusionsThe CBCT/3D‐replica protocol showed no significant differences in the clinical or radiological outcomes. The high success rates in both groups suggest that the protocol is valuable primarily for optimizing surgical efficiency and as a training tool for clinicians.
Bias and precision of predicted densities of overabundant kangaroo populations
Authors: Hone Jim , Snape Melissa 
Published: November 2024

SummaryValidated predictions of wildlife population density would be very useful for managers of overabundant wildlife and their effects on biodiversity. In this study such predictions were generated by modelling population dynamics of 18 non‐culled populations of Eastern Grey Kangaroos (Macropus giganteus) across small biodiversity conservation reserves in Canberra. Predictions were validated using three analyses of independent, out‐of‐sample, data from 11 populations which were non‐culled or culled. Association (analysis 1) showed observed and predicted densities were significantly positively correlated (R2 = 0.79, P = 0.045, n = 5) with unbiased slope and y intercept for non‐culled populations, though observed and predicted densities of culled populations were unrelated (R2 = 0.32, P = 0.24, n = 6). Coverage (analysis 2) showed predicted densities were within the 95% confidence interval of observed densities in five of five non‐culled populations and four of six culled populations, with one underestimate and one overestimate in the latter group. Bias (analysis 3) showed the mean bias (=observed – predicted) was 0.18 (±0.23 SE) kangaroos/ha for non‐culled and 0.08 (±0.23 SE) for culled populations. The results have been used to adjust kangaroo management approaches in Canberra as part of adaptive management.
Understanding How, Why and for Whom Link Work Interventions Promote Access in Community Healthcare Settings in the United Kingdom: A Realist Review
Authors: Golby Rebecca , Lobban Fiona , Laverty Louise , Velemis Kyriakos , Aggarwal Vishal R. , Berry Katherine , Morris Abby , Elliott Emma , Harris Rebecca , Ross Al , Chew‐Graham Carolyn A. , Budd Miranda , McGowan Linda , Shiers David , Caton Neil , Lodge Chris , French Paul , Griffiths Robert , Palmier‐Claus Jasper 
Published: November 2024

ABSTRACTIntroductionInequity in access to healthcare in the United Kingdom can have a profound impact on people's ability to manage their health problems. Link work interventions attempt to overcome the socioeconomic and structural barriers that perpetuate health inequalities. Link workers are typically staff members without professional clinical qualifications who support patients to bridge the gap between services. However, little is currently known about how and why link work interventions might be effective. This realist review attempts to understand the contexts and resultant mechanisms by which link work interventions affect access to community healthcare services.MethodsThe authors completed a systematic search of empirical literature in Embase, CINAHL, Medline, PsychInfo and SocIndex, as well as grey literature and CLUSTER searches. Context, mechanism and outcome (CMO) configurations were generated iteratively in consultation with an expert panel and grouped into theory areas.ResultsThirty‐one eligible manuscripts were identified, resulting in nine CMO configurations within three theory areas. These pertained to adequate time in time‐pressured systems; the importance of link workers being embedded across multiple systems; and emotional and practical support for link workers.ConclusionAlthough link work interventions are increasingly utilised across community healthcare settings, the contexts in which they operate vary considerably, triggering a range of mechanisms. The findings suggest that careful matching of resources to patient need and complexity is important. It affords link workers the time to develop relationships with patients, embed themselves in local communities and referring teams, and develop knowledge of local challenges.Patient or Public ContributionThe team included people with lived experience of mental health conditions and a carer who were involved at all stages of the review.
Suppressing the thermal conduction in glass–ceramic foams by controlling crystallization
Authors: Thomsen Line , Yue Yuanzheng , Østergaard Martin B. 
Published: November 2024

AbstractGlass‐based insulating materials have attracted considerable attention owing to their tailorable properties. It is known that the thermal conductivity of glass ceramics can be greatly influenced by varying their crystallinity. However, the mechanism of such influence in glass–ceramic foams remains poorly understood. In this study, we demonstrate our new findings regarding the correlation between thermal conductivity and crystallinity in silicate glass–ceramic foams. The foams were produced by mixing ZrO2‐containing soda‐lime glass powder with CaCO3 as foaming agent and foam them using a thermochemical approach. ZrO2 was introduced as a nucleation agent. The crystallinity of the foams was varied by adjusting the heating protocol, i.e., by varying temperature, time, and number of heating cycles. The glass–ceramic foams exhibited relative crystallinities of <30%. The identity of the crystalline phases in the glass–ceramic foams varies with crystallinity. Specifically, cristobalite diminished, but devitrite grew with increasing crystallinity. It was observed that the crystallinity had a nonmonotonic impact on the thermal conductivity of the glass–ceramic foams. The optimum crystallinity for achieving the lowest thermal conductivity was 8–10%, resulting in an approximately 20% lower thermal conductivity compared to noncrystalline. Our findings have implications for the future design of glass–ceramic foams.
Prenatal drivers of microglia vulnerability in the adult
Authors: Tagliatti Erica , Bizzotto Matteo , Morini Raffaella , Filipello Fabia , Rasile Marco , Matteoli Michela 
Published: November 2024

SummaryEnvironmental insults during early development heavily affect brain trajectories. Among these, maternal infections, high‐fat diet regimens, and sleep disturbances pose a significant risk for neurodevelopmental derangements in the offspring. Notably, scattered evidence is starting to emerge that also paternal lifestyle habits may impact the offspring development. Given their key role in controlling neurogenesis, synaptogenesis and shaping neuronal circuits, microglia represent the most likely suspects of mediating the detrimental effects of prenatal insults. For some of these environmental triggers, like maternal infections, ample literature evidence demonstrates the central role of microglia, also delineating the specific transcriptomic and proteomic profiles induced by these insults. In other contexts, the analysis of microglia is still in its infancy. Fostering these studies is needed to define microglia as potential therapeutic target in the frame of disorders consequent to maternal immune activation.
Investigating the correlation of hip circumference to cardiovascular disease and type‐2 diabetes using Mendelian randomization
Authors: Liu Hongtao , Li Zhaoyu , Yan Su , Ming Shaopeng 
Published: November 2024

ABSTRACTObjectiveThis study aimed to assess the correlation between hip circumference (HC) and the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus using Mendelian randomization (MR) to overcome observational study limitations.DesignMR analysis utilized genetic variation from the MR Base in a two‐sample analysis. Three methods were employed: MR‐Egger regression, weighted median estimator, and inverse variance weighting (IVW).SettingData was acquired from MR Base, a platform summarizing genome‐wide association study (GWAS) data for MR research.Main Outcome MeasuresPublicly available summary statistics datasets from GWAS meta‐analyses were used, with HC and HC adjusted for body mass index (BMI) as exposures. Data for CVD and type 2 diabetes mellitus were obtained as outcomes.ResultsResults indicated a positive causal relationship between HC and CVD (IVW: P = 1.84e‐07, OR: 1.37, 95% CI: 1.22–1.54) as well as type 2 diabetes mellitus (IVW: P = 0.04, OR: 1.62, 95% CI: 1.02–2.56), independent of BMI. However, HC after BMI adjustment showed no significant causal relationship with CVD (IVW: P = 0.05, OR: 1.09, 95% CI: 1.00–1.19) and exhibited a negative association with type 2 diabetes mellitus (IVW: P = 0.00, OR: 0.76, 95% CI: 0.66–0.88), suggesting a protective effect against type 2 diabetes mellitus.ConclusionsAfter adjusting for BMI, adipose tissue concentrated in the hip region showed a protective effect against type 2 diabetes mellitus but not against CVD. These findings offer insights into diabetes prevention and treatment strategies, and may inform plastic surgery procedures. Further research is needed to validate these findings and explore underlying mechanisms.