bluuebunny/crossref_metadata_2025 huggingface dataset:
A cross‐sectional CBCT assessment of the relative position of one‐piece titanium‐zirconium mini‐implants placed for mandibular overdentures using non‐guided surgery
Authors: Leles Cláudio Rodrigues , de Oliveira Moura‐Neto Leuçon , Silva Jésio Rodrigues , Nascimento Lays Noleto , Curado Thalita Fernandes Fleury , Costa Nadia Lago , Schimmel Martin , McKenna Gerald
Published: July 2024

Objective

To assess the relative position of mini‐implants to retain a mandibular overdenture, according to the surgical protocol, technical and anatomical factors.

Methods

Mandibular cone‐beam computed tomography (CBCT) scans were analyzed for 73 patients who received four one‐piece titanium‐zirconium mini‐implants. Drilling was performed using a 1.6 mm needle drill and a 2.2 mm Pilot Drill, according to the bone density with a surgical stent. Post‐insertion CBCT images in DICOM format were analyzed using the E‐Vol‐DX software with BAR filters. Divergence angle between implants and between implants and the overdenture path of insertion was measured using CliniView 10.2.6 software.

Results

Divergence between implants ranged from 0° to 22.3° (mean = 4.2; SD = 3.7) in the lateral and from 0° to 26.2° (mean = 5.3; SD = 4.1) in the frontal projections (p < .001). Only 1 (0.2%) and 3 (0.7%) of the measurements were higher than 20° in the lateral and frontal views, respectively. The mean angulations between the implant and the path of insertion for the overdenture were 9.3° (SD = 7.5) and 4.0° (SD = 2.9) for the lateral and frontal views, respectively (p < .001). Regression analyses showed a significant association between the divergence of implants and the frontal view projection (p < .001), greater distance between the paired implants (p = .017), the flapped surgical protocol (p = .002), higher final insertion torque (p = .011), and deeper preparation with the needle drill (p < .001).

Conclusions

The mini‐implants were placed with low divergence angles and satisfactory parallelism. Factors including shorter distances between the implants, higher density bone, and a flapless surgical approach all contributed positively to improved parallelism of the mini‐implants.
Examining the structure of plant–lemur interactions in the face of imperfect knowledge
Authors: Tonos Jadelys , Papinot Bastien , Park Daniel S. , Raelison Mihajatiana , Ramaroson Herilantonirina , Stubbs Jessica , Razafindratsima Onja H.
Published: July 2024

Biotic interactions, such as plant–animal seed dispersal mutualisms, are essential for ecosystem function. Such interactions are threatened by the possible extinction of the animal partners. Using a data set that includes plant–lemur interactions across Madagascar, we studied the current state of knowledge of these interactions and their structure to determine which plant species are most at risk of losing dispersal services due to the loss of lemurs. We found substantial gaps in understanding of plant–lemur interactions; data were substantially skewed toward a few lemur species and locations. There was also a large gap in knowledge on the interactions of plants and small‐bodied or nocturnal lemurs and lemurs outside a few highly studied locations. Of the recorded interactions, a significant portion occurred between lemurs and endemic plants, rather than native or introduced plants. We also found that lemur species tended to primarily consume closely related plant species. Such interaction patterns may indicate the threats to Malagasy endemic plants and highlight how lemur population loss or reductions could affect plant phylogenetic diversity. When examining the impacts of lemur extinction, losing critically endangered species left 164 plant species with no known lemur frugivore partners. Despite phylogenetic patterns in lemur diet, plants for which the only known lemur frugivore is critically endangered were not closely related. These results emphasize the need for further studies to complete our knowledge on these essential interactions and to inform conservation priorities.
Designing cities for everyday nature
Authors: Visintin Casey , Garrard Georgia E. , Weisser Wolfgang W. , Baracco Mauro , Hobbs Richard J. , Bekessy Sarah A.
Published: July 2024

The motivations for incorporating nature into the design of cities have never been more compelling. Creating experiences with nature that occur every day (everyday nature) in cities could help reverse the fate of many threatened species and connect people with nature and living cultural traditions. However, this requires more than just urban greening; it involves ensuring daily doses of nature in a way that also supports nonhuman organisms. A major shift in the way nature is conceived of and is made part of the design of cities is required. Principles include reconsidering nature as a development opportunity rather than a constraint and eliminating offsetting of biodiversity site values. Processes include using biodiversity‐sensitive design frameworks and establishing meaningful professional engagement among ecologists, planners, and designers. Challenges include design obstacles, conflicts between nature and people (e.g., safety, disease, and noise) that require careful management, and socioeconomic and political considerations (e.g., Global North vs. Global South). Research to interrogate the multiple benefits of nature in cities can complement experimental interventions, ultimately supporting better urban design and creating much more resiliently built environments for people and nature.
Chronic kidney disease in type 2 diabetes: The size of the problem, addressing residual renal risk and what we have learned from the CREDENCE trial
Authors: Chaudhry Khuram , Karalliedde Janaka
Published: July 2024

Chronic kidney disease (CKD) associated with type 2 diabetes (T2DM) is a global challenge; progression to end‐stage kidney disease (ESKD) and increased risk of cardiovascular disease (CVD) associated with advancing nephropathy are a significant source of morbidity, mortality, and healthcare expenditure. Until recently, renin‐angiotensin system (RAS) blockade was the mainstay of pharmacotherapy in diabetic kidney disease (DKD), representing a therapeutic paradigm shift towards interventions that delay disease progression independently of antihypertensive effects. However, a significant residual risk of DKD progression persisted in patients established on RAS blockade, highlighting the need for additional treatment options. Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors, originally licensed as glucose‐lowering agents in people with T2DM, serendipitously demonstrated beneficial renal and cardiovascular outcomes in clinical trials designed primarily to evaluate their cardiovascular safety. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial was the first to study the effect of SGLT2 inhibition on a primary composite renal endpoint of ESKD, doubling of serum creatinine, or renal or cardiovascular death in 4401 people with T2DM and CKD established on RAS blockade. The trial was stopped early due to efficacy, demonstrating a 30% relative risk reduction in the primary endpoint in the canagliflozin group (hazard ratio 0.70, 95% confidence interval 0.59–0.82; p = 0.00001). Through discussion of the primary analysis from CREDENCE, and selected post hoc analyses, we review the significant benefits highlighted by this landmark study, its role in shaping clinical guidelines, and in re‐establishing interest in interventions that reduce the residual risk of progression of DKD, alongside its interrelation with cardiovascular morbidity and heart failure. We also provide a brief narrative summary of key renal outcome trials since CREDENCE, which indicate emerging avenues for pharmacotherapy beyond SGLT2 inhibition.
WONOEP appraisal: Modeling early onset epilepsies
Authors: De Meulemeester Ann‐Sofie , Reid Christopher , Auvin Stéphane , Carlen Peter L. , Cole Andrew J. , Szlendak Roza , Di Sapia Rossella , Moshé Solomon L. , Sankar Raman , O'Brien Terence J. , Baulac Stéphanie , Henshall David C. , Akman Özlem , Galanopoulou Aristea S.
Published: July 2024

Epilepsy has a peak incidence during the neonatal to early childhood period. These early onset epilepsies may be severe conditions frequently associated with comorbidities such as developmental deficits and intellectual disability and, in a significant percentage of patients, may be medication‐resistant. The use of adult rodent models in the exploration of mechanisms and treatments for early life epilepsies is challenging, as it ignores significant age‐specific developmental differences. More recently, models developed in immature animals, such as rodent pups, or in three‐dimensional organoids may more closely model aspects of the immature brain and could result in more translatable findings. Although models are not perfect, they may offer a more controlled screening platform in studies of mechanisms and treatments, which cannot be done in pediatric patient cohorts. On the other hand, more simplified models with higher throughput capacities are required to deal with the large number of epilepsy candidate genes and the need for new treatment options. Therefore, a combination of different modeling approaches will be beneficial in addressing the unmet needs of pediatric epilepsy patients. In this review, we summarize the discussions on this topic that occurred during the XVI Workshop on Neurobiology of Epilepsy, organized in 2022 by the Neurobiology Commission of the International League Against Epilepsy. We provide an overview of selected models of early onset epilepsies, discussing their advantages and disadvantages. Heterologous expression models provide initial functional insights, and zebrafish, rodent models, and brain organoids present increasingly complex platforms for modeling and validating epilepsy‐related phenomena. Together, these models offer valuable insights into early onset epilepsies and accelerate hypothesis generation and therapy discovery.
A novel transformer attention‐based approach for sarcasm detection
Authors: Khan Shumaila , Qasim Iqbal , Khan Wahab , Aurangzeb Khursheed , Khan Javed Ali , Anwar Muhammad Shahid
Published: July 2024

Sarcasm detection is challenging in natural language processing (NLP) due to its implicit nature, particularly in low‐resource languages. Despite limited linguistic resources, researchers have focused on detecting sarcasm on social media platforms, leading to the development of specialized algorithms and models tailored for Urdu text. Researchers have significantly improved sarcasm detection accuracy by analysing patterns and linguistic cues unique to the language, thereby advancing NLP capabilities in low‐resource languages and facilitating better communication within diverse online communities. This work introduces UrduSarcasmNet, a novel architecture using cascaded group multi‐head attention, which is an innovative deep‐learning approach that employs cascaded group multi‐head attention techniques to enhance effectiveness. By employing a series of attention heads in a cascading manner, our model captures both local and global contexts, facilitating a more comprehensive understanding of the text. Adding a group attention mechanism enables simultaneous consideration of various sub‐topics within the content, thereby enriching the model's effectiveness. The proposed UrduSarcasmNet approach is validated with the Urdu‐sarcastic‐tweets‐dataset (UST) dataset, which has been curated for this purpose. Our experimental results on the UST dataset show that the proposed UrduSarcasmNet framework outperforms the simple‐attention mechanism and other state‐of‐the‐art models. This research significantly enhances natural language processing (NLP) and provides valuable insights for improving sarcasm recognition tools in low‐resource languages like Urdu.
The quality of the stepfather–child relationship in sole and joint physical custody
Authors: Steinbach Anja , Augustijn Lara , de Bel Vera
Published: July 2024

Objective

This study examines whether the quality of the stepfather–child relationship differs among sole physical custody (SPC) and joint physical custody (JPC) families and compares the association between the father–child and the stepfather–child relationship across the two physical custody arrangements.

Background

An increasing number of families opt for JPC after separation or divorce. Because children in JPC families spend more time with their biological father than children in mother SPC families, the question arises whether JPC affects the quality of the stepfather–child relationship.

Method

We investigated 279 SPC and 182 JPC stepfather families with children aged 1 to 14 from the Family Models in Germany study. Ordinary least squares regression models and interaction effects were estimated.

Results

The quality of the stepfather–child relationship was generally high in both SPC and JPC families and did not differ between the two arrangements. The father–child relationship was positively, albeit weakly, associated with the stepfather–child relationship in both arrangements, indicating spillover effects.

Conclusion

JPC does not affect the quality of the stepfather–child relationship.

Implications

This study does not provide any evidence that JPC is an ill‐suited physical custody arrangement when considering the quality of relationships in stepfamilies.
Resilience Against All Odds: How Refugee Women From Ukraine Find Courage Through Transnational Families
Authors: Dryjanska Laura , Sanchez Jamie N. , Hagues Rachel
Published: July 2024

The recent war in Ukraine has prompted a global focus on refugees and their ability to successfully overcome adversity. This article focuses on the factors that foster resilience in women refugees. Refugee resilience depends on external environments as much as on internal strength, both of which relate to the nature of transnational families that stretch across at least two countries and rely on the family member's internal capacity to address the challenge of maintaining ties, alongside their external resources available in their circumstances. A qualitative study was conducted in November 2022 with 11 women refugees from Ukraine interviewed in Warsaw, Poland. Eight themes that contribute to resilience in women refugees were identified, including (1) family (in particular, intergenerational family solidarity), (2) community, (3) artistic expression and artisan creation, (4) connection to nature and environment, (5) access to mental health professionals, (6) work, (7) faith and spirituality and (8) hope for the future. Dominant, overarching narratives included the safety and well‐being of participants’ children, overcoming adversities for the sake of their sons and daughters and facing daily struggles related to providing for their family.
Enhanced Removal of Brine From Porous Structures by Supercritical CO2
Authors: Erramuspe Iris Beatriz Vega , Asafu‐Adjaye Osei , Rojas‐Márquez Melissa , Via Brian , Sastri Bhima , Banerjee Sujit
Published: July 2024

Supercritical CO2 (sCO2) removes water from brine held in pumice stone at levels well above the solubility of water in sCO2. The higher water removal results from a combination of passive emulsification of water in sCO2 and viscous fingering of sCO2 through the saturated pumice. This leads to higher levels of salt deposition than that expected from solubility considerations alone. These deposits could impact the injectivity of sCO2 as well as its movement in the subsurface. The finding that the water concentration in sCO2 is not necessarily capped at the solubility limit should influence the parametrization of injection models.
Histopathological assessment of the viability of hepatic alveolar echinococcosis
Authors: Robers Selina , Reinehr Michael , Haibach Lillemor , Furrer Eva , Cincera Annina , Kronenberg Philipp Andreas , Eichenberger Ramon Marc , Deplazes Peter , Deibel Ansgar , Müllhaupt Beat , Weber Achim
Published: July 2024

Aims

Infections by the larval stage of the tape worms Echinococcus multilocularis and Echinococcus granulosus s.l. are potentially fatal zoonoses affecting humans as dead‐end hosts. Histopathological evaluation of hepatic echinococcosis is an integral part of patient management, including the distinction between alveolar (AE) and cystic echinococcosis (CE), which are associated with different disease courses and treatments. To improve histopathological assessment of Echinococcus lesions, we aimed to develop robust criteria to evaluate their viability and decay.

Methods and results

Histomorphological criteria for determining parasitic viability based on the morphology of parasite structures and different stages of their decay were defined based on a clinically and molecularly defined cohort comprising 138 specimens from 112 patients (59 AE and 53 CE); 618 AE lesions were assessed for histopathological viability comparing haematoxylin and eosin (H&E) staining with mAbEm18 and mAbEm2G11 immunostaining. Moreover, parasite viability was systematically mapped in cross‐sections of five additional AE lesions. Protoscoleces in CE and AE displayed variable states of degeneration. Albendazole had no significant effect on the morphology of parasite structures. Viability assessment revealed high agreement between H&E and mAbEm18, but not mAbEm2G11 staining, suggesting mAbEm18 staining as reliable for parasite viability assessment. H&E and mAbEm18 staining displayed a central–peripheral gradient of parasite viability and decay across parasitic lesions, with decayed cystic lesions located more towards the lesion centre while the most viable cystic lesions were located more peripherally.

Conclusions

Histopathological criteria corroborated by mAbEm18 staining provide a simple and reliable tool to assess the viability of AE lesions, knowledge of which is a valuable decision‐making tool for further treatment.
Clinicopathologic and molecular study of superficial CD34‐positive fibroblastic tumours mimicking atypical fibrous histiocytoma (dermatofibroma)
Authors: Wakefield Craig B , Mertens Fredrik , Fletcher Christopher D M , Anderson William J
Published: July 2024

Aims

Superficial CD34‐positive fibroblastic tumour (SCD34FT) is an uncommon but distinctive low‐grade neoplasm of the skin and subcutis that shows frequent CADM3 expression by immunohistochemistry (IHC). In this study, prompted by an index case resembling ‘atypical fibrous histiocytoma (FH)’ that was positive for CADM3 IHC, we systematically examined a cohort of tumours previously diagnosed as ‘atypical FH’ by applying CADM3 and fluorescence in situ hybridization (FISH) for PRDM10 rearrangement, to investigate the overlap between these tumour types.

Methods and Results

Forty cases of atypical FH were retrieved, including CD34‐positive tumours (n = 20) and CD34‐negative tumours (n = 20). All tumours were stained for CADM3. All CADM3‐positive tumours were evaluated by FISH to assess for PRDM10 rearrangement. Eleven CD34‐positive tumours (11/20, 55%) coexpressed CADM3 and were reclassified as SCD34FT. None (0/20) of the CD34‐negative atypical FH were CADM3‐positive. Reclassified SCD34FT (10/11) arose on the lower extremity, with frequent involvement of the thigh (n = 8). Features suggestive of atypical FH were observed in many reclassified cases including variable cellularity, spindled morphology, infiltrative tumour margins, collagen entrapment, epidermal hyperpigmentation, and acanthosis. Variably prominent multinucleate giant cells, including Touton‐like forms, were also present. An informative FISH result was obtained in 10/11 reclassified tumours, with 60% (6/10) demonstrating PRDM10 rearrangement.

Conclusion

A significant subset of tumours that histologically resemble atypical FH, and are positive for CD34, coexpress CADM3 and harbour PRDM10 rearrangement, supporting their reclassification as SCD34FT. Awareness of this morphologic overlap and the application of CADM3 IHC can aid the distinction between SCD34FT and atypical FH.
Proanthocyanidin surface preconditioning of dental pulp stem cell spheroids enhances dimensional stability and biomineralization in vitro
Authors: Yang Shengyan , Leung Andy Yu Pan , Wang Zheng , Yiu Cynthia Kar Yung , Dissanayaka Waruna Lakmal
Published: July 2024

Aim

Lack of adequate mechanical strength and progressive shrinkage over time remain challenges in scaffold‐free microtissue‐based dental pulp regeneration. Surface collagen cross‐linking holds the promise to enhance the mechanical stability of microtissue constructs and trigger biological regulations. In this study, we proposed a novel strategy for surface preconditioning microtissues using a natural collagen cross‐linker, proanthocyanidin (PA). We evaluated its effects on cell viability, tissue integrity, and biomineralization of dental pulp stem cell (DPSCs)‐derived 3D cell spheroids.

Methodology

Microtissue and macrotissue spheroids were fabricated from DPSCs and incubated with PA solution for surface collagen cross‐linking. Microtissue viability was examined by live/dead staining and 3‐(4,5‐dimethylthiazol‐2‐yl)−2,5‐diphenyltetrazolium bromide (MTT) assay, with transverse dimension change monitored. Microtissue surface stiffness was measured by an atomic force microscope (AFM). PA‐preconditioned microtissues and macrotissues were cultured under basal or osteogenic conditions. Immunofluorescence staining of PA‐preconditioned microtissues was performed to detect dentin sialophosphoprotein (DSPP) and F‐actin expressions. PA‐preconditioned macrotissues were subjected to histological analysis, including haematoxylin–eosin (HE), alizarin red, and Masson trichrome staining. Immunohistochemistry staining was used to detect alkaline phosphatase (ALP) and dentin matrix acidic phosphoprotein 1 (DMP‐1) expressions.

Results

PA preconditioning had no adverse effects on microtissue spheroid viability and increased surface stiffness. It reduced dimensional shrinkage for over 7 days in microtissues and induced a larger transverse‐section area in the macrotissue. PA preconditioning enhanced collagen formation, mineralized nodule formation, and elevated ALP and DMP‐1 expressions in macrotissues. Additionally, PA preconditioning induced higher F‐actin and DSPP expression in microtissues, while inhibition of F‐actin activity by cytochalasin B attenuated PA‐induced dimensional change and DSPP upregulation.

Conclusion

PA surface preconditioning of DPSCs spheroids demonstrates excellent biocompatibility while effectively enhancing tissue structure stability and promoting biomineralization. This strategy strengthens tissue integrity in DPSC‐derived spheroids and amplifies osteogenic differentiation potential, advancing scaffold‐free tissue engineering applications in regenerative dentistry.
Dynamic bending analysis of metallized silicon nitride substrate during thermal cycling via digital image correlation
Authors: Ngo Minh Chu , Miyazaki Hiroyuki , Hirao Kiyoshi , Ohji Tatsuki , Fukushima Manabu
Published: July 2024

Digital image correlation (DIC) method was employed to analyze the dynamic bending of a metallized Si3N4 substrate in thermal cycles ranging from −40°C to 250°C. The substrate was monitored by DIC over several consecutive cycles, spanning from 0 to 2501. Three DIC measurement intervals, specifically during 999–1001, 1999–2001, and 2499–2501 cycles, were selected to analyze the bending behavior in response to temperature fluctuations. By the scanning acoustic microscope (SAM), the substrate revealed negligible delamination after 1001 cycles, light delamination after 2001 cycles, and serious delamination post‐2501 cycles. The dynamic bending remained unchanged during 999–1001 cycles. A curve with a negative bending was observed during 1999–2001 cycles, with a peak curvature of .024 mm−1 at −40°C; the negative bending intensified with a curvature reaching .050 mm−1 at −40°C during 2499–2501 cycles. The bending curve then decreased during the heating phase and returned to a non‐bent state at elevated temperatures. The bending curve reversed to positive at 250°C during thermal cycles from 2499 to 2501. The bending behavior throughout thermal cycles was discussed in relation to the asymmetric delamination observed on both sides of the substrate, as well as the distribution of delamination.
Viscous crack healing in soda–lime–magnesium–silicate–ZrO2 glass matrix composites
Authors: Blaeß Carsten , Müller Ralf
Published: July 2024

The present study investigates the influence of the crystal volume content on viscous crack healing in glass ceramic glass sealants. To ensure constant microstructure during healing, soda–lime–magnesium silicate glass matrix composites with varied volume fractions of ZrO2 filler particles were used. Crack healing was studied on radial cracks induced by Vickers indentation, which were stepwise annealed to monitor the healing progress by confocal laser scanning microscopy. Confirming previous studies, healing of radial cracks in pure glass was found delayed by global flow phenomena like crack widening and crack edge and tip rounding to minimize the sample surface. With increasing ZrO2 filler content, these global flow phenomena were progressively inhibited whereas local flow phenomena like sharp crack tip healing could still occur. As a result, crack healing was even accelerated by filler particles up to a maximum filler content of 17 vol% whereas crack healing was fully suppressed only at 33 vol% filler content.
Selective laser sintering and spark plasma sintering of (Zr,Nb,Ta,Ti,W)C compositionally complex carbide ceramics
Authors: Trinh Lanh , Hua Zilong , Bawane Kaustubh , He Lingfeng , Malakkal Linu , Chen Xin , Wadle Luke , Lu Yongfeng , Cui Bai
Published: July 2024

Two advanced manufacturing processes, spark plasma sintering (SPS) and selective laser sintering (SLS), have been developed for synthesis of (Zr,Nb,Ta,Ti,W)C compositionally complex carbide (CCC) via reactive sintering of a powder mixture of constitute monocarbides. X‐ray diffraction analysis confirmed that the single‐phase CCC can be formed by both SPS and SLS. While a homogenous microstructure with uniform metal element distributions was developed during SPS, three‐layer microstructures with a thin TiC‐rich layer and two TaC‐rich layers along with a TiO2‐rich surface layer containing W nanoparticles were formed during SLS. In addition, cellular structures with W, Zr, and Ti element segregation and dislocations on cell boundaries were observed in the SLS‐CCC sample, indicating the effect of nonequilibrium conditions on microstructure formation during laser melting followed by rapid cooling and solidification process. Compared to the SPS‐CCC sample, the SLS‐CCC showed enhanced hardness and reduced thermal conductivity, which may be related to their unique cellular structures.
Binary transition metal oxide: A novel and efficient catalyst for the synthesis of boron nitride nanotubes
Authors: Wang Heng , Zhu Tianbin , Dai Yajie , Sang Shaobai , Li Yawei , Fu Zhengyi
Published: July 2024

A novel binary transition metal oxide (NiFe2O4) nanosphere catalyst with a diameter of 500 nm has been synthesized by the hydrothermal reaction, which can efficiently catalyze the formation of hexagonal boron nitride nanotubes (BNNTs) with high‐yield and large aspect ratio. Based on the temperature dependence of the product phase composition and microstructure, combined with results generated using single‐component catalysts, the BNNTs formation process can be summarized as follows: NiFe2O4 reacts with NH3 to generate Fe0.64Ni0.36, which dissolves to form a liquid‐phase Ni‐Fe alloy at high temperatures, where the B component in the precursor and the N atom formed by the decomposition of NH3 diffuse on the surface of the Ni‐Fe alloy; when the concentration of B and N exceed the saturation threshold, hollow BNNTs containing catalyst at the tips are precipitated. The formation process is dominated by a vapor‐liquid‐solid mechanism with tip‐growth mode, where the synergistic catalytic effect of the Ni‐Fe binary system promotes a high yield of large aspect ratio BNNTs.
Novel candidate metastasis‐associated genes for synovial sarcoma
Authors: Zhao Zhiqing , Niu Jianfang , Wang Jichuan , Zhang Ranxin , Liang Haijie , Ma Yingteng , Ferrena Alexander , Wang Wei , Yang Rui , Geller David S. , Guo Wei , Ren Tingting , Hoang Bang H. , Tang Xiaodong , Yan Taiqiang
Published: July 2024

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with poor prognosis due to late recurrence and metastasis. Metastasis is an important prognostic factor of SS. This study aimed to identify the core genes and mechanisms associated with SS metastasis. Microarray data for GSE40021 and GSE40018 were obtained from the Gene Expression Omnibus database. 186 differentially expressed genes (DEGs) were identified. The biological functions and signalling pathways closely associated with SS metastasis included extracellular matrix (ECM) organization and ECM‐receptor interaction. Gene set enrichment analysis showed that the terms cell cycle, DNA replication, homologous recombination and mismatch repair were significantly enriched in the metastasis group. Weighted gene co‐expression network analysis identified the most relevant module and 133 hub genes, and 31 crossover genes were identified by combining DEGs. Subsequently, four characteristic genes, EXO1, NCAPG, POLQ and UHRF1, were identified as potential biomarkers associated with SS metastasis using the least absolute shrinkage and selection operator algorithm and validation dataset verification analysis. Immunohistochemistry results from our cohort of 49 patients revealed visible differences in the expression of characteristic genes between the non‐metastatic and metastatic groups. Survival analysis indicated that high expression of characteristic genes predicted poor prognosis. Our data revealed that primary SS samples from patients who developed metastasis showed activated homologous recombination and mismatch repair compared to samples from patients without metastasis. Furthermore, EXO1, NCAPG, POLQ and UHRF1 were identified as potential candidate metastasis‐associated genes. This study provides further research insights and helps explore the mechanisms of SS metastasis.
The effect of the HMGB1/RAGE/TLR4/NF‐κB signalling pathway in patients with idiopathic epilepsy and its relationship with toxoplasmosis
Authors: Soytürk Hayriye , Önal Cansu , Kılıç Ümit , Türkoğlu Şule Aydın , Ayaz Erol
Published: July 2024

This study aims to investigate the relationship between toxoplasmosis and this pathway, which may be effective in the formation of epilepsy by acting through the HMGB1/RAGE/TLR4/NF‐κB signalling pathway in patients with idiopathic epilepsy. In the study, four different experimental groups were formed by selecting Toxoplasma gondii IgG positive and negative patients with idiopathic epilepsy and healthy controls. Experimental groups were as follows: Group 1: Epilepsy+/Toxo− (E+, T−) (n = 10), Group 2: Epilepsy−/Toxo− (E−, T−) (n = 10), Group 3: Epilepsy−/Toxo+ (E−, T+) (n = 10), Group 4: Epilepsy+/Toxo+ (E+, T+) (n = 10). HMGB1, RAGE, TLR4, TLR1, TLR2, TLR3, IRAK1, IRAK2, IKBKB, IKBKG, BCL3, IL1β, IL10, 1 L8 and TNFα mRNA expression levels in the HMGB/RAGE/TLR4/NF‐κB signalling pathway were determined by quantitative simultaneous PCR (qRT‐PCR) after collecting blood samples from all patients in the groups. Statistical analysis was performed by one‐way ANOVA followed by LSD post‐hoc tests, and p < 0.05 was considered to denote statistical significance. The gene expression levels of HMGB1, TLR4, IL10, IL1B, IL8, and TLR2 were significantly higher in the G1 group than in the other groups (p < 0.05). In the G3 group, RAGE and BCL3 gene expression levels were significantly higher than in the other groups (p < 0.05). In the G4 group, however, IRAK2, IKBKB, and IKBKG gene expression levels were significantly higher than in the other groups (p < 0.05). HMGB1, TLR4, IRAK2, IKBKB, IL10, IL1B, IL1B, and IL8 in this signalling pathway are highly expressed in epilepsy patients in G1 and seizures occur with the stimulation of excitatory mechanisms by acting through this pathway. The signalling pathway in epilepsy may be activated by HMGB1, TLR4, and TLR2, which are considered to increase the level of proinflammatory cytokines. In T. gondii, this pathway is activated by RAGE and BCL3.
Summary data‐based Mendelian randomization and single‐cell RNA sequencing analyses identify immune associations with low‐level LGALS9 in sepsis
Authors: Yang Yongsan , Dong Lei , Li Yanguo , Huang Ye , Zeng Xiaoxi
Published: July 2024

Sepsis is one of the major challenges in intensive care units, characterized by the complexity of the host immune status. To gain a deeper understanding of the pathogenesis of sepsis, it is crucial to study the phenotypic changes in immune cells and their underlying molecular mechanisms. We conducted Summary data‐based Mendelian randomization analysis by integrating genome‐wide association studies data for sepsis with expression quantitative trait locus data, revealing a significant decrease in the expression levels of 17 biomarkers in sepsis patients. Furthermore, based on single‐cell RNA sequencing data, we elucidated potential molecular mechanisms at single‐cell resolution and identified that LGALS9 inhibition in sepsis patients leads to the activation and differentiation of monocyte and T‐cell subtypes. These findings are expected to assist researchers in gaining a more in‐depth understanding of the immune dysregulation in sepsis.
Deciphering lung adenocarcinoma prognosis and immunotherapy response through an AI‐driven stemness‐related gene signature
Authors: Ye Bicheng , Hongting Ge , Zhuang Wen , Chen Cheng , Yi Shulin , Tang Xinyan , Jiang Aimin , Zhong Yating
Published: July 2024

Lung adenocarcinoma (LUAD) is a leading cause of cancer‐related deaths, and improving prognostic accuracy is vital for personalised treatment approaches, especially in the context of immunotherapy. In this study, we constructed an artificial intelligence (AI)‐driven stemness‐related gene signature (SRS) that deciphered LUAD prognosis and immunotherapy response. CytoTRACE analysis of single‐cell RNA sequencing data identified genes associated with stemness in LUAD epithelial cells. An AI network integrating traditional regression, machine learning, and deep learning algorithms constructed the SRS based on genes associated with stemness. Subsequently, we conducted a comprehensive exploration of the connection between SRS and both intrinsic and extrinsic immune environments using multi‐omics data. Experimental validation through siRNA knockdown in LUAD cell lines, followed by assessments of proliferation, migration, and invasion, confirmed the functional role of CKS1B, a top SRS gene. The SRS demonstrated high precision in predicting LUAD prognosis and likelihood of benefiting from immunotherapy. High‐risk groups classified by the SRS exhibited decreased immunogenicity and reduced immune cell infiltration, indicating challenges for immunotherapy. Conversely, in vitro experiments revealed CKS1B knockdown significantly impaired aggressive cancer phenotypes like proliferation, migration, and invasion of LUAD cells, highlighting its pivotal role. These results underscore a close association between stemness and tumour immunity, offering predictive insights into the immune landscape and immunotherapy responses in LUAD. The newly established SRS holds promise as a valuable tool for selecting LUAD populations likely to benefit from future clinical stratification efforts.
Assessment of soft and hard tissue changes following micro crestal flap—Alveolar ridge preservation and augmentation at molar extraction sites in patients with stage III/IV periodontitis: A randomized controlled trial
Authors: Zhang Haoyun , Xu Tao , Wei Yiping , Wei Ning , Han Ziyao , Hu Wenjie
Published: July 2024

Aim

This study aimed to assess hard and soft tissue contour changes following micro crestal flap‐alveolar ridge preservation (MCF‐ARP) and natural healing (NH) in periodontally compromised molar extraction sites and to analyse the feasibility and need for bone augmentation during implant therapy.

Materials and Methods

Fifty‐six patients with 70 sites were randomized into two groups at the site level (35 sites from 31 patients in the test group and 35 sites from 29 patients in the control group). Among whom, four patients contributed one tooth to the control group and one tooth to the test group. Hard tissue indicators were measured using cone beam computed tomography performed before tooth extraction and 6 months after surgery. Soft tissue contour changes were assessed using intraoral scanning performed before and immediately after surgery and also 2 weeks and 1, 3 and 6 months after surgery.

Results

Six months after surgery, the MCF‐ARP group showed less resorption in buccal bone height (p = .032) and greater augmentation in central bone height (p = .001) and ridge width (p = .009). The mean, vertical and horizontal collapse of buccal soft tissue contour in the MCF‐ARP group were 0.95 mm (p = .010), 0.61 mm (p = .019) and 0.56 mm (p = .013) less than that in the NH group, respectively. There were significantly (p = .007) fewer sites in the MCF‐ARP group than in the NH group (0% vs. 26.7%) for staged bone augmentation and more sites that could be treated with simple implant procedure in the MCF‐ARP group than in the NH group (71.9% vs. 56.6%).

Conclusions

Compared with NH, MCF‐ARP reduced bone resorption in periodontally compromised molar extraction sites and maintained the buccal soft tissue contour. MCF‐ARP reduces the need for complex bone augmentation procedures in implant therapy. Trial registration: Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on 4 February 2022, Version 1.0.
Efficacy of long‐term low carbohydrate diets for patients with type 2 diabetes: A systematic review and meta‐analysis
Authors: Ichikawa Takahiro , Okada Hiroshi , Hironaka Junya , Nakajima Hanako , Okamura Takuro , Majima Saori , Senmaru Takafumi , Ushigome Emi , Nakanishi Naoko , Hamaguchi Masahide , Joo Erina , Shide Kenichiro , Fukui Michiaki
Published: July 2024

Aims/Introduction

Efficacy of long‐term low‐carbohydrate diets (LCD) to improve glycemic management for type 2 diabetes remains controversial. Thus, we investigated the association between long‐term LCD and glycemic control in individuals with type 2 diabetes.

Materials and Methods

We searched PubMed, Embase and the Cochrane Database for articles published up to June 2023, and included randomized controlled trials conducted on LCD interventions for >12 months in adults with type 2 diabetes. Primary outcome was the difference in glycated hemoglobin between long‐term LCD and control groups. Additionally, we evaluated the differences in changes in systolic and diastolic blood pressure, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglyceride, and weight between long‐term LCD and control groups.

Results

Six studies were identified and met the inclusion criteria. This study did not show significant differences in changes in glycated hemoglobin between long‐term LCD and control diets (standardized mean difference −0.11, 95% confidence interval −0.33 to 0.11, P = 0.32). As with glycemic control, there were no significant differences in the changes in weight loss, blood pressure, and low‐density lipoprotein cholesterol between long‐term LCD and control diets. However, long‐term LCD were associated with greater elevation in high‐density lipoprotein cholesterol (standardized mean difference 0.22, 95% confidence interval 0.04–0.41; P = 0.02) and decrease in triglyceride (standardized mean difference −0.19; 95% confidence interval −0.37 to 0.02; P = 0.03) than that in control diets.

Conclusions

Our findings suggest efficacy of long‐term LCD in treating dyslipidemia in individuals with type 2 diabetes, but do not recommend long‐term LCD for glycemic control in the individuals.
The effect of anxiety on all‐cause dementia: A longitudinal analysis from the Hunter Community Study
Authors: Khaing Kay , Dolja‐Gore Xenia , Nair Balakrishnan R. , Byles Julie , Attia John
Published: July 2024

Background

Anxiety is common, however, the effect of chronicity of anxiety on dementia has not been explored. This study aims to assess the longitudinal relationship between chronic versus resolved versus new onset anxiety, and all‐cause dementia risk.

Methods

A total of 2132 participants with mean age 76 years from the Hunter Community Study were recruited. Anxiety was measured using Kessler Psychological Distress Scale (K10). Dementia was defined as per International Classification of Disease—10 codes. The Fine–Gray subdistribution hazard model was computed to assess dementia risk, while adjusting for the competing risk of death.

Results

Chronic anxiety and new onset anxiety at follow‐up were associated with all‐cause dementia risk (HR 2.80, 95% CI 1.35–5.72 and HR 3.20, 95% CI 1.40–7.45 respectively) with an average time to dementia diagnosis of 10 years (SD = 1.7) whereas resolved anxiety was not. In subgroup analyses, these results were driven particularly by chronic and new anxiety among participants below the age of 70 years (HR 4.58, 95% CI 01.12–18.81 and HR 7.21, 95%CI 1.86–28.02 respectively). Sensitivity analyses imputing missing data and addressing reverse causation gave very similar results.

Conclusion

Chronic and new anxiety were associated with increased risk of all‐cause dementia, and this association was significant in those 70 years and younger. However, the resolved anxiety at follow‐up reduced the risk, similar to that of the non‐exposed group. These results suggest that timely management of anxiety may be a viable strategy in reducing the risk of dementia.
Bone microstructure as an indicator of digging ability in moles (Talpidae, Eulipotyphla)
Authors: Nakai Daichi , Yokohata Yasushi
Published: July 2024

Talpid moles (Talpidae, Eulipotyphla) are mammals highly specialised in burrowing using their forelimbs. Fossoriality has allowed moles to expand their ecological niche by enabling access to subterranean resources and spaces. This specialisation in burrowing has led to adaptations in the forelimb bones of moles for humeral rotation digging, a distinctive strategy unparalleled among other diggers. While bone robustness has been examined in moles through external morphology, the adaptation of bone microstructure to digging strategy remains unclear. Based on two assumptions, (1) the humerus of moles is subjected to a torsional load due to humeral rotation digging, and (2) the magnitude of torsional load correlates with the compactness of the substrate in which the individuals can dig, we hypothesised that humeral rotation digging influences bone microstructure. Comparative analyses of transverse sections from the humeri and femora of three mole species (Mogera imaizumii, Mogera wogura and Urotrichus talpoides; Talpidae) and an outgroup eulipotyphlan (Suncus murinus; Soricidae) revealed that (1) vascular canals distributed in the humeri of moles align more predominantly circumferential along the bone walls, indicating an adaptation to the torsion generated by humeral rotation digging, and (2) the laminarity of vascular canals, particularly in Mogera species compared with Urotrichus, potentially reflects differences in the magnitude of load due to substrate compactness during digging. The aligned vascular canals are distinctive traits not observed in mammals employing other digging strategies. This suggests that vascular canal laminarity can be an indicator of not only humeral rotation digging in fossorial animals, but also the variation of eco‐spaces in talpid species.
Concentrated growth factor intradermal injection assisted super‐thin flap expansion for repairing skin defects: A randomized, single blinded, split‐site study
Authors: Liang Rongzhou , Yang Sifen , Song Meihua , Kuang Baizeng , Li Kun , Huang Danli , Wang Chunmei
Published: July 2024

Background

The super‐thin skin flap formed by skin and soft tissue expansion has large area and good ductility, so it can be used to repair skin defects. However, because the flap is thin, the blood flow in the dermis of the super‐thin expanded flap is weakened, and flap rupture and necrosis after secondary flap transfer may occur.

Objective

To compare the skin thickness difference between the expanded ultrathin flaps injected with concentrated growth factor (CGF) and the blank group or saline group.

Methods

From June 2021 to December 2023, 10 patients (44 sites) with large‐area scars or skin tumors were treated, and a single center half randomized controlled trial was conducted. The test site of expander implantation was divided into three groups: intradermal injection of CGF group, normal saline group and blank group. The same amount of expansion was performed every 1–2 weeks, and CGF or normal saline was injected into the dermis every 4 weeks, a total of three times. After 2–3 months of expansion, color Doppler ultrasound was used to measure the skin thickness of each group.

Results

Compared with the blank group, the skin thickness of CGF group was 1.75 ± 0.08 mm, and that of BLA blank group was 1.42 ± 0.07 mm, with statistically significant difference (p < 0.0001); In the other group, compared with the saline group, the skin thickness of the CGF group was 1.54 ± 0.08 mm, and the average skin thickness of the saline group was 1.40 ± 0.08 mm, with significant difference between the two groups (p = 0.0067).

Conclusion

CGF intradermal injection can increase the skin thickness of super‐thin skin flap in the process of soft tissue expansion, which is a safe and effective auxiliary method of skin expansion.
Comparison of therapeutic agents' short‐term effects on facial and scalp actinic keratosis: A network meta‐analysis
Authors: Gupta Aditya K. , Bamimore Mary A. , Wang Tong , Polla Ravi Shruthi , Haas‐Neil Sandor , Martin George , Piguet Vincent , Talukder Mesbah
Published: July 2024

Background

Care for actinic keratosis (AK) can be improved with more knowledge on the relative of effect of indicated therapies.

Objectives

Using network meta‐analyses, we quantitatively determined the comparative “short‐term” effects of interventions in adults with facial and scalp AK.

Methods

On February 28, 2023, evidence from the peer‐reviewed literature was systematically obtained from OVID, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. We analyzed data from studies published in English, of a trial design, and investigating the effect of an actinic keratosis monotherapy. Patient complete clearance, patient partial clearance or lesion‐specific clearance across adults were analyzed at 8–12 weeks after therapy. Patient complete clearance pertained to proportion of participants who experienced complete clearance of actinic keratosis lesions; patient partial clearance corresponded to percentage of subjects who achieved at least 75% clearance of actinic keratosis lesions; lesion‐specific clearance represented the percentage of all lesions that were cleared. In the main (i.e., base) analyses, nodes were analyzed only at the level of the agent.

Results

Data from a total of 84 studies were used—across which 22 active agents were identified. Estimates of interventions' surface under the cumulative ranking curve rankings and (pairwise) relative effects were estimated. Across the three outcomes, fluorouracil 5% was ranked the most effective.

Conclusions

Our work is the first to provide information on covariate‐adjusted relative effects of actinic keratosis therapies— including the more recently reported treatments—for the face and scalp; this knowledge may help physicians and patients make more informed decisions.