bluuebunny/crossref_metadata_2025 huggingface dataset:
Volumetric analysis of the hypothalamic subunits in obstructive sleep apnea
Authors: Mohammadi Mahdi , Oghabian Mohammad Ali , Ghaderi Sadegh , Jalali Maryam , Samadi Shahram
Published: September 2024

Background

Obstructive sleep apnea (OSA) is a prevalent sleep disorder that is associated with structural brain damage and cognitive impairment. The hypothalamus plays a crucial role in regulating sleep and wakefulness. We aimed to evaluate hypothalamic subunit volumes in patients with OSA.

Methods

We enrolled 30 participants (15 patients with OSA and 15 healthy controls (HC)). Patients with OSA underwent complete overnight polysomnography (PSG) examination. All the participants underwent MRI. The hypothalamic subunit volumes were calculated using a segmentation technique that trained a 3D convolutional neural network.

Results

Although hypothalamus subunit volumes were comparable between the HC and OSA groups (lowest p = .395), significant negative correlations were found in OSA patients between BMI and whole left hypothalamus volume (R = –0.654, p = .008), as well as between BMI and left posterior volume (R = –0.556, p = .032). Furthermore, significant positive correlations were found between ESS and right anterior inferior volume (R = 0.548, p = .042), minimum SpO2 and the whole left hypothalamus (R = 0.551, p = .033), left tubular inferior volumes (R = 0.596, p = .019), and between the percentage of REM stage and left anterior inferior volume (R = 0.584, p = .022).

Conclusions

While there were no notable differences in the hypothalamic subunit volumes between the OSA and HC groups, several important correlations were identified in the OSA group. These relationships suggest that factors related to sleep apnea severity could affect hypothalamic structure in patients.
Strategic resilience nexus: Connecting pioneering and sustainability orientations
Authors: Parra‐Requena Gloria , García‐Villaverde Pedro M. , Ruiz‐Ortega María José , Córcoles‐Muñoz Mateo M.
Published: September 2024

This work analyzes, under a strategic approach, the role of organizational resilience (OR) in connecting pioneering orientation (PO) and sustainability orientation (SO), thus filling a significant and unexplored gap in the literature. The empirical study was conducted on a sample of 223 companies in the cultural tourism industry in Spain. The results show a total mediating effect of OR in the relationship between PO and SO in its economic, environmental, and social dimensions and a partial effect in the case of the cultural dimension. The study highlights the U‐shaped curvilinear relationship between PO and OR, reflecting a brake on the growth of OR when companies have a strong tendency to enter the market early. Companies should adopt the role of early followers to strengthen resilience and achieve a strong strategic commitment to sustainability.
A stretchable human lung‐on‐chip model of alveolar inflammation for evaluating anti‐inflammatory drug response
Authors: Richter Clémentine , Latta Lorenz , Harig Daria , Carius Patrick , Stucki Janick D. , Hobi Nina , Hugi Andreas , Schumacher Paul , Krebs Tobias , Gamrekeli Alexander , Stöckle Felix , Urbschat Klaus , Montalvo Galia , Lautenschläger Franziska , Loretz Brigitta , Hidalgo Alberto , Schneider‐Daum Nicole , Lehr Claus‐Michael
Published: September 2024

This study describes a complex human in vitro model for evaluating anti‐inflammatory drug response in the alveoli that may contribute to the reduction of animal testing in the pre‐clinical stage of drug development. The model is based on the human alveolar epithelial cell line Arlo co‐cultured with macrophages differentiated from the THP‐1 cell line, creating a physiological biological microenvironment. To mimic the three‐dimensional architecture and dynamic expansion and relaxation of the air‐blood‐barrier, they are grown on a stretchable microphysiological lung‐on‐chip. For validating the in vitro model, three different protocols have been developed to demonstrate the clinically established anti‐inflammatory effect of glucocorticoids to reduce certain inflammatory markers after different pro‐inflammatory stimuli: (1) an inflammation caused by bacterial LPS (lipopolysaccharides) to simulate an LPS‐induced acute lung injury measured best with cytokine IL‐6 release; (2) an inflammation caused by LPS at ALI (air‐liquid interface) to investigate aerosolized anti‐inflammatory treatment, measured with chemokine IL‐8 release; and (3) an inflammation with a combination of human inflammatory cytokines TNFα and IFNγ to simulate a critical cytokine storm leading to epithelial barrier disruption, where the eventual weakening or protection of the epithelial barrier can be measured. In all cases, the presence of macrophages appeared to be crucial to mediating inflammatory changes in the alveolar epithelium. LPS induction led to inflammatory changes independently of stretch conditions. Dynamic stretch, emulating breathing‐like mechanics, was essential for in vitro modeling of the clinically relevant outcome of epithelial barrier disruption upon TNFα/IFNγ‐induced inflammation.
PIK3CA mutational status in tissue and plasma as a prognostic biomarker in HR+/HER2− breast cancer
Authors: Terán Eduardo , Lozano Rebeca , Rodríguez César A. , Abad Mar , Figuero Luis , Muñoz José Antonio , Cigarral Belén , Rodrígues Aline , Sancho Magdalena , Gómez M. Asunción , Morchón Daniel , Montero Juan Carlos , Sayagués José María , Ludeña M. Dolores , Fonseca Emilio
Published: September 2024

Introduction

Hotspots (HS) mutations in the PIK3CA gene may lead to poorer oncological outcomes and endocrine resistance in advanced breast cancer (BC), but their prognostic role in early‐stage disease remains controversial. The overall agreement within plasma and tissue methods has not been well explored. Our aim was to correlate tissue and plasma approaches and to analyze the prognostic impact of PIK3CA mutations (PIK3CAm) in HR+/HER2− BC.

Methods

A retrospective and unicentric analysis of PIK3CA mutational status in tissue and plasma samples by Cobas®PIK3CA Mutation Kit in patients with HR+/HER2− BC.

Results

We analyzed 225 samples from 161 patients with luminal BC. PIK3CA mutations were identified in 62 patients (38.5%), of which 39.6% were found in tissue and 11.8% in plasma. In advanced disease, plasma and tissue correlation rate was performed in 64 cases, with an overall agreement of 70.3%. Eighty patients were treated with CDK4/6 inhibitors + endocrine therapy. We observed a moderately worse progression‐free survival (PFS) in PIK3CAm versus wild‐type (WT) (24 m vs. 30 m; HR = 1.39, p = 0.26). A subanalysis was carried out based on exons 9 and 20, which showed a statistically poorer PFS in PIK3CAm exon 9 versus 20 population (9.7 m vs. 30.3 m; HR = 2.84; p = 0.024). Furthermore, detection of PIK3CAm in plasma was linked to a worse PFS vs PIK3CAm detection just in tissue (12.4 vs. 29.3; HR = 2.4; p = 0.08).

Conclusions

Our findings suggest the PIK3CA evaluation in tissue as the diagnostic method of choice, however, additional investigations are required to improve the role of liquid biopsy in the PIK3CA assessment. PIK3CAm show worse outcomes in advanced luminal BC, especially in exon 9 mutation carriers, despite visceral involvement, prior exposure to endocrine therapy or detection of PIK3CAm in plasma, with an unclear prognosis in early‐stage disease. Nonetheless, this should be validated in a prospective cohort study.
Quality and nutritional attributes of whole einkorn flour and its suitability for fresh noodle production compared to whole wheat flour
Authors: Kim Jeongeon , Moon Yujin , Kim Hyungseop , Gőksen Gűlden , Kweon Meera
Published: September 2024

Background and Objectives

This study investigated the physicochemical properties, particle size, pasting properties, phenolic acids, carotenoid content, and fresh noodle quality characteristics of whole einkorn flour (WEF) in comparison with whole wheat flour (WWF). Three WEF samples from different cultivation regions in Turkey were analyzed.

Findings

The WEFs exhibited significant variations in all quality characteristics compared to WWF, influenced by different einkorn growing environments. Phenolic acid and carotenoid contents, along with antioxidant activity, were highest in WEF1 and WEF2, highlighting their potential nutritional benefits. Noodles made from WEF3 demonstrated quality equivalent to that of WWF, although their protein content and nutritional value were relatively lower than those of WEF1 and WEF2.

Conclusions

This research demonstrates the potential of WEF for fresh noodle production with quality comparable to WWF. The nutritional value varies by cultivation area, emphasizing the importance of selecting appropriate cultivars and growing conditions for optimal results.

Significance and Novelty

This study highlights, for the first time, the nutritional value and quality characteristics of WEF influenced by growing areas, impacting its suitability, equivalent to WWF, for producing fresh noodles.
Lactic acid bacteria‐fermented Chlamydomonas reinhardtii as an innovative ingredient to produce microalgae‐enriched steamed bread
Authors: Jin Zhiqiang , Gu Yaoguang , Zhang Wen
Published: September 2024

Background and Objectives

Chlamydomonas reinhardtii (C. reinhardtii) is recognized as a sustainable source of high‐quality protein. This study aimed to assess the potential application of C. reinhardtii for producing microalgae‐fortified steamed bread. To reduce the inherent green color and volatile compounds of the microalgae, lactic acid bacteria (LAB) fermentation was applied as a pretreatment method for C. reinhardtii. Subsequently, both unfermented (unFC) and fermented C. reinhardtii (FC) were added to steamed bread formulations (4%, 8%, 12%, and 16% wheat flour substitution).

Findings

The results showed that the incorporation of unFC into steamed bread had a dose‐dependent negative impact on the dough fermentation performance and the quality of steamed bread, including volume, texture, and sensory attributes, rendering the steamed bread unacceptable. Fermentation altered the amino acid profile of C. reinhardtii, caused the color to shift from green to red (a*, −14.7 vs. 7.0), and reduced unpleasant volatile components. Further, fermentation reduced the negative impact of microalgae incorporation, especially at substitution levels of 4% and 8%, which manifested as an increased dough fermentation volume and improved bread volume with reduced crumb firmness of the steamed bread. However, in sensory analysis, the steamed bread that contained 4% FC had an overall acceptability similar to the control sample.

Conclusions

Microalgae‐enriched steamed bread could be produced by incorporating up to 4% FC to improve its nutritional profiles while maintaining overall sensory acceptability by the consumers.

Significance and Novelty

LAB fermentation of C. reinhardtii is a feasible strategy to address the sensory and structural challenges that hinder the incorporation of algae into food products.
Pd Nanoparticle Supported on N‐Doped Carbon Derived from Sodium Alginate/Melamine Blends as Efficient Heterogeneous Catalyst for Heck Reactions
Authors: Zhou Jie , Wu Yuanyuan , Liu Yonghong , Li Na , Yang Zhen , Ying Jiadi , Ren Xiaorong , Zhang Tao , Xu Wei , Chen Jinyang , Cao Xingzhong , Yu Runsheng , Zeng Minfeng
Published: September 2024

N‐doped porous carbon shows great potential in the field of heterogenous supports due to its high porosity, large surface area, rich active sites, and strong chelation with catalytic active metals species. Herein, we successfully prepared a novel N‐doped porous carbon derived from sodium alginate/melamine blends (SAMNC) with different mass ratio through a simple carbonization and activation process. Hierarchical porous structure of the derived N‐doped carbon has been confirmed with the SEM, TEM, and N2 adsorption characterization. After Na2PdCl4 solution impregnation and further reduction process, Pd0 nanoparticles have been uniformly immobilized on the SAMNC support to produce novel Pd@SAMNC catalyst. The optimal Pd@SAMNC‐0.6 possesses a high N content (5.13%), Pd content (5.90%), large BET specific surface area of 1884.5 m2·g−1. Positron annihilation lifetime spectroscopy (PALS) investigation of the porous carbon materials provided the sub‐nano level microporous information proofs of Pd@SAMNC‐0.6 had the capability to provide more active sites for reactions than commercial Pd supported on activated carbon (Pd@AC). Pd@SAMNC‐0.6 catalyst showed superior catalytic efficiency in Heck coupling reaction between aromatic halides and alkenes and can be recycled for 17 runs without significant decrease in catalytic efficiency.
Leveraging Natural Product‐Inspired Antifungals to Investigate the Mechanism of Action of Peniciaculin A
Authors: Wilt Ingrid K. , Demeritte Adrian R. , Kim Alexander T. , Wang Weiwei , Wuest William M.
Published: September 2024

Ubiquinone mimics known as quinone outside inhibitors (QoIs) are one of the most prominent fungicides used to protect crops in the agricultural industry. Due to chemotype similarities with known QoIs, peniciaculin A, a triaryl natural product, was proposed to exhibit similar broad spectrum antifungal activity against phytopathogens. Instability of the tertiary alcohol and phenol motif, however, prompted exploration of the antifungal properties of simplified analogues to probe possible overlap in mechanism of action between the natural product and QoIs. Peniciaculin A inspired analogues mimicking known QoI scaffolds displayed broad spectrum antifungal activity while those containing scaffolds dissimilar to QoIs possessed negligible bioactivity. These activity profiles suggest peniciaculin A is likely acting as a QoI.
Programmed death‐ligand 1 expression in patients with primary or secondary myelofibrosis
Authors: Ibrahim Moayed , Murphree Catherine , Patel Kirtesh , Mastrodomenico Matthew , Saba Nakhle S. , Safah Hana , Schmid Janet , Socola Francisco
Published: September 2024

Background

It has been described in mice models that myeloproliferative neoplasm (MPN) with JAK2‐V617F mutation has an increased expression of programmed death‐ligand 1 (PD‐L1) in megakaryocytes leading to cancer immune evasion by inhibiting the T‐lymphocytes.

Aims

To quantify and compare the PD‐L1 expression on bone marrow (BM) of patients with MPN JAK2 positive, negative, and normal controls.

Methods

We collected BM of patients with MPN JAK2 positive, negative and normal controls from 1990 to 2019. We also created a scoring system to quantify PD‐L1 expression in megakaryocytes.

Results

We obtained 14 BM with JAK2 positive PMF, 5 JAK2 negative PMF, and 10 patients with normal BM biopsies. PD‐L1 expression was higher in the JAK2 positive group compared with the control group with a score of 212.6 versus 121.1 (t‐value 2.05, p‐value 0.025). In addition, the score was higher in the PMF group regardless of JAK2 mutational status when compared with the control group with score of 205.9 versus 121.1 (t‐value 2.12, p‐value 0.021). There was no difference in the PD‐L1 score between the JAK2 negative versus the control group 187.2 versus 121.1 (t‐value 1.02, p‐value 0.162).

Conclusion

These findings suggest that PMF patients with a JAK2 mutation have a higher PD‐L1 expression in megakaryocytes compared with the control group. We postulate that the combination of checkpoint and JAK2 inhibitors may be an active treatment option in JAK2 mutated PMF given the higher PD‐L1 expression.
Experiences Using Nonpharmacological Interventions for Chronic Fatigue: A Focus Group Study of Long‐Term Survivors of Young Adult Cancers With Fatigue
Authors: Stub Trine , Mathisen Marleen , Thorsen Lene , Kiserud Cecilie E. , Lie Hanne C.
Published: September 2024

Background

Cancer‐related fatigue is a common and distressing late effect of cancer that can persist for decades after treatment completion. Although negatively affecting survivors' quality of life, few, if any, efficacious interventions for persistent, or chronic, fatigue exist.

Aims

To inform future interventions, we explored how long‐term, young adult cancer survivors (YACSs) with chronic fatigue live with, and manage their fatigue over time, including their experiences with nonpharmacological interventions (NPIs) for chronic fatigue.

Methods and Results

We conducted a qualitative focus group study with 15 YACSs (13 women) with chronic fatigue, on average 7.3 years post‐diagnosis. The YACS were identified and recruited through a nationwide health survey of cancer survivors (the NOR‐CAYACS study). Systematic content analysis was used to identify recurrent themes. Analysis revealed five themes: (1) manifestation of fatigue, detailing chronic fatigue experiences; (2) impact on daily life, highlighting the necessity to balance rest and activity, affecting relationships; (3) NPIs, where walks in nature were notably beneficial; (4) barriers to fatigue management, including energy deficits, treatment‐related bodily changes, and self‐care prioritization challenges; (5) facilitators to fatigue management, emphasizing the need for regular breaks, self‐care practices, and the importance of fatigue management education.

Conclusion

This study offers novel insights into the lived experiences of YACSs with chronic fatigue, a subject scarcely examined in prior research. Our findings highlight the significant impact of chronic fatigue and the individualized strategies YACSs use to cope. The research emphasizes the need for personalized interventions to support chronic fatigue management, marking a critical step forward in addressing this often‐overlooked issue in survivorship care. Future research should focus on tailored approaches to improve YACSs' quality of life.
The Unified Protocol or Dialectical Behaviour Therapy? Considerations for Choosing Between Two Evidence‐Based Transdiagnostic Psychotherapies for Complex Patients
Authors: Cassiello‐Robbins Clair , Ritschel Lorie A. , Mochrie Kirk D. , Edwards‐Powell Becca , Byars Kathryn
Published: September 2024

The advent of multiple transdiagnostic treatments in recent decades has advanced the field of clinical psychology while also raising questions for clinicians and patients about how to decide between treatments and how to best deliver a chosen treatment. The purpose of this paper is to review two prominent transdiagnostic treatments that target emotion dysregulation: dialectical behaviour therapy and the unified protocol for transdiagnostic treatment for emotional disorders. First, we review the theoretical underpinnings, research support and proposed mechanisms of action for these treatments. Next, we discuss patient and therapist variables that might indicate which treatment is more appropriate for a given patient and discuss decision‐making guidelines to help make this determination with an emphasis on complex patients who may present with risk and/or clinical comorbidities. Finally, we discuss areas for future research that can help further ensure we work to match patients to the treatment that is most likely to benefit them.
A comprehensive study on in situ stress field characteristics and changes in rock mechanical properties in deep mines in northeastern Yunnan, China
Authors: Wang Hui , Sun Bangtao , Cao Cong , Yu Shibo , Wang He , Yuan Ye , Zhong Hua
Published: September 2024

The Maoping lead–zinc mining area is a significant metal mine site in northeastern Yunnan. In this study, both hydraulic fracturing in situ stress testing and ultrasonic imaging logging were first carried out in the mining area. Second, 930 focal mechanism solutions and 231 sets of stress data near the mining area were collected. Then, the variations in the type of in situ stress field, the magnitude of in situ stress, the direction of horizontal principal stress, and the ratio of lateral pressure were analyzed to characterize the distribution of the in situ stress field. On this basis, a new method using borehole breakouts and drilling‐induced fractures was proposed to determine the stress direction. Finally, the evolution of the mechanical properties of dolomite with burial depth was analyzed and the influence of rock mechanical properties on the distributions of the in situ stress field was explored. The results show that the in situ stress in the mining area is σH > σV > σh, indicating a strike–slip stress state. The in situ stress is high in magnitude, and its value increases with burial depth. The maximum and minimum horizontal lateral stress coefficients are stabilized at approximately 1.22 and 0.73, respectively. The direction of the maximum horizontal principal stress is NW, mainly ranging from N58.44° W to N59.70° W. The stress field inferred from the focal mechanism solution is in good agreement with the test results. The proportion of structural planes with dip angles between 30° and 75° exceeds 80%, and the dip direction of the structural planes is mainly NW to NWW. The line density of structural planes shows high density in shallow areas and low density in deep areas. More energy tends to be accumulated in rocks with higher elastic modulus and strength, leading to higher in situ stress levels. These findings are of significant reference for mine tunnel layout, support design optimization, and disaster prevention.
Climatic niche shifts and ecological sky‐island dynamics in Mesoamerican montane birds
Authors: Rocha‐Méndez Alberto , Prieto‐Torres David A. , Sánchez‐González Luis A. , Navarro‐Sigüenza Adolfo G.
Published: September 2024

An ongoing challenge in evolutionary and ecological research focuses on testing biogeographic hypotheses for the understanding of both species' distributional patterns and of the factors influencing range limits. In this study, we described the climatic niches of Neotropical humid montane forest birds through the analysis of factors driving their evolution at inter‐ and intraspecific levels; and tested for differences among allopatric lineages within Aulacorhynchus, Chlorospingus, Cardellina, and Eupherusa. We employed ecological niche models (ENMs) along with an ordination approach with kernel smoothing to perform niche overlap analyses and test hypotheses of niche equivalence/similarity among lineages. In addition, we described the potential distributions of each lineage during the Late Pleistocene climate fluctuations, identifying historical range expansions, connectivity, and stability. Overall, we observed differences in environmental variables influencing climatic requirements and distributional patterns for our selected species. We detected the highest values of niche overlap mainly between Eupherusa and some Chlorospingus lineages. At both interspecific and intraspecific levels, sister lineages showed non‐identical environmental niches. Our results offer weak support to a moist forest model, in which populations followed the expansion and contraction cycles of montane forests, leading to a lack of niche conservatism among lineages (they tend to occupy not identical climatic environments) throughout Mesoamerica. Therefore, historical climatic conditions may act as ecological barriers determining the distributional ranges of these species.
Macroinvertebrates but Not Diatoms Are Affected by Streamflow Alteration Below Hydropower Diversions
Authors: Spitale Daniel , Fezzi Marco , Zorzi Nadia , Slomp Elisabeth , Rigotti Sandro , Borrini Alex , Bilous Olena , Cantonati Marco
Published: September 2024

River regulation due to dams and other intake structures has impacted the hydrology, water quality and biology of rivers worldwide. The release of minimum flows still represents the strategy aimed at maintaining certain aspects of the original flow patterns. However, there remains a limited understanding of the consequences of artificially induced flows on water quality and aquatic life across various types of rivers. This study was conducted in Trentino (south‐eastern Alps, Italy) in 60 perennial river reaches (400–2005 m a.s.l.), all located downstream of water abstractions for different hydropower plants. The main goal of this research was to compare the effect of different residual flows on macroinvertebrates and diatoms. The overall effect of discharge was low but still significant only for macroinvertebrates, whereas diatoms were affected mostly by the water chemistry. Both groups responded to the substrate composition and to the hydromorphology, which in turn resulted to be strongly correlated. The biotic indices, originally developed to respond to pollution, were unaffected by the flow reduction, raising concerns about the potential consequences that assessment based on this approach may have on the evaluation of ecological flow. This study emphasizes the importance of considering the broader ecological context in which flow alterations occur, particularly the interaction of hydromorphology and substrate, in understanding their impact on aquatic biota.
Testing food web theory in a large lake: The role of body size in habitat coupling in Lake Michigan
Authors: Maitland Bryan M. , Bootsma Harvey A. , Bronte Charles R. , Bunnell David B. , Feiner Zachary S. , Fenske Kari H. , Fetzer William W. , Foley Carolyn J. , Gerig Brandon S. , Happel Austin , Höök Tomas O. , Keppeler Friedrich W. , Kornis Matthew S. , Lepak Ryan F. , McNaught A. Scott , Roth Brian M. , Turschak Benjamin A. , Hoffman Joel C. , Jensen Olaf P.
Published: September 2024

The landscape theory of food web architecture (LTFWA) describes relationships among body size, trophic position, mobility, and energy channels that serve to couple heterogenous habitats, which in turn promotes long‐term system stability. However, empirical tests of the LTFWA are rare and support differs among terrestrial, freshwater, and marine systems. Further, it is unclear whether the theory applies in highly altered ecosystems dominated by introduced species such as the Laurentian Great Lakes. Here, we provide an empirical test of the LTFWA by relating body size, trophic position, and the coupling of different energy channels using stable isotope data from species throughout the Lake Michigan food web. We found that body size was positively related to trophic position, but for a given trophic position, organisms predominately supported by pelagic energy had smaller body sizes than organisms predominately supported by nearshore benthic energy. We also found a hump‐shaped trophic relationship in the food web where there is a gradual increase in the coupling of pelagic and nearshore energy channels with larger body sizes as well as higher trophic positions. This highlights the important role of body size and connectivity among habitats in structuring food webs. However, important deviations from expectations are suggestive of how species introductions and other anthropogenic impacts can affect food web structure in large lakes. First, native top predators appear to be flexible couplers that may provide food web resilience, whereas introduced top predators may confer less stability when they specialize on a single energy pathway. Second, some smaller bodied prey fish and invertebrates, in addition to mobile predators, coupled energy from pelagic and nearshore energy channels, which suggests that some prey species may also be important integrators of energy pathways in the system. We conclude that patterns predicted by the LTFWA are present in the face of species introductions and other anthropogenic stressors to a degree, but time‐series evaluations are needed to fully understand the mechanisms that promote stability.
Integrin beta‐like 1 is regulated by DNA methylation and increased in heart failure patients
Authors: Kerrigan Lauren , Edgar Kevin , Russell‐Hallinan Adam , Cappa Oisin , Glezeva Nadezhda , Galan‐Arriola Carlos , Oliver Eduardo , Ibanez Borja , Baugh John , Collier Patrick , Ledwidge Mark , McDonald Ken , Simpson David , Das Sudipto , Grieve David J. , Watson Chris J.
Published: September 2024

Aims

Dynamic alterations in cardiac DNA methylation have been implicated in the development of heart failure (HF) with evidence of ischaemic heart disease (IHD); however, there is limited research into cell specific, DNA methylation sensitive genes that are affected by dysregulated DNA methylation patterns. In this study, we aimed to identify DNA methylation sensitive genes in the ischaemic heart and elucidate their role in cardiac fibrosis.

Methods

A multi‐omics integrative analysis was carried out on RNA sequencing and methylation sequencing on HF with IHD (n = 9) versus non‐failing (n = 9) left ventricular tissue, which identified Integrin beta‐like 1 (ITGBL1) as a gene of interest. Expression of Itgbl1 was assessed in three animal models of HF; an ischaemia‐reperfusion pig model, a myocardial infarction mouse model and an angiotensin‐II infused mouse model. Single nuclei RNA sequencing was carried out on heart tissue from angiotensin‐II infused mice to establish the expression profile of Itgbl1 across cardiac cell populations. Subsequent in vitro analyses were conducted to elucidate a role for ITGBL1 in human cardiac fibroblasts. DNA pyrosequencing was applied to assess ITGBL1 CpG methylation status in genomic DNA from human cardiac tissue and stimulated cardiac fibroblasts.

Results

ITGBL1 was >2‐fold up‐regulated (FDR adj P = 0.03) and >10‐fold hypomethylated (FDR adj P = 0.01) in human HF with IHD left ventricular tissue compared with non‐failing controls. Expression of Itgbl1 was up‐regulated in three isolated animal models of HF and showed conserved correlation between increased Itgbl1 and diastolic dysfunction. Single nuclei RNA sequencing highlighted that Itgbl1 is primarily expressed in cardiac fibroblasts, while functional studies elucidated a role for ITGBL1 in cardiac fibroblast migration, evident in 50% reduced 24 h fibroblast wound closure occurring subsequent to siRNA‐targeted ITGBL1 knockdown. Lastly, evidence provided from DNA pyrosequencing supports the theory that differential expression of ITGBL1 is caused by DNA hypomethylation.

Conclusions

ITGBL1 is a gene that is mainly expressed in fibroblasts, plays an important role in cardiac fibroblast migration, and whose expression is significantly increased in the failing heart. The mechanism by which increased ITGBL1 occurs is through DNA hypomethylation.
Innate T‐cell‐derived IL‐17A/F protects from bleomycin‐induced acute lung injury but not bleomycin or adenoviral TGF‐β1‐induced lung fibrosis in mice
Authors: Moog Marie T. , Baltes Melina , Röpke Tina , Aschenbrenner Franziska , Maus Regina , Stolper Jennifer , Jonigk Danny , Prinz Immo , Kolb Martin , Maus Ulrich A.
Published: September 2024

The pathobiology of IL‐17 in lung fibrogenesis is controversial. Here we examined the role of IL‐17A/F in bleomycin (BLM) and adenoviral TGF‐β1‐induced lung fibrosis in mice. In both experimental models, WT and IL17af−/− mice showed increased collagen contents and remodeled lung architecture as assessed by histopathological examination, suggesting that IL‐17A/F is dispensable for lung fibrogenesis. However, IL17af−/− mice responded to the BLM challenge with perturbed lung leukocyte subset recruitment. More specifically, bleomycin triggered angiocentric neutrophilic infiltrations of the lung accompanied by increased mortality of IL17af−/− but not WT mice. WT bone marrow transplantation failed to correct this phenotype in BLM‐challenged IL17af−/− mice. Conversely, IL17a/f−/− bone marrow transplantation → WT did not perturb lung leukocytic responses upon BLM. At the same time, IL17af−/− mice treated with recombinant IL‐17A/F showed an attenuated lung inflammatory response to BLM. Together, the data show that the degree of BLM‐driven acute lung injury was critically dependent on the presence of IL‐17A/F, while in both models, the fibrotic remodeling process was not.
Review on Synthesis Methods of Carbon Nanotubes as Activated Carbon Composites Based on Biomass for Supercapacitors in Electric Vehicles
Authors: Wiyono Apri , Mohd Zulkifli Nurin Wahidah , Wan Daud Wan Mohd Ashri , Sukrawan Yusep , Anggrainy Rani , Syafrinaldy Ade , Nolandy Henry , Abidin Asroful , Sukarno Ragil , Aziz Muhammad
Published: September 2024

Biomass can be converted into carbon through carbonization processes (pyrolysis and hydrothermal carbonization) and activation (physical and chemical). The resulting carbon has a high potential as a supercapacitor electrode material due to its porous structure, which supports rapid ion transport. Various methods have been developed to extract or transform biomass into porous carbon. One of the newly developed nanocarbon materials is carbon nanotubes (CNTs) because they have advantages in terms of mechanical, physical, chemical, and electrical properties. This review discusses various kinds of CNT synthesis as activated carbon composites for supercapacitors. The synthesis of these CNTs can be conducted through chemical and physical methods, including arc discharge, laser vaporization, and chemical vapor deposition (CVD). This work reviews various methods of CNT synthesis and analyzes the best methods to be used as composites for supercapacitors for electric vehicles. It is concluded that CVD is the best method for synthesizing CNTs. Its main advantage is that CNTs can be used directly without purification unless the catalyst particles need to be removed. However, further experimental studies are required to find the most optimal conditions for each composite from a type of mesoporous activated carbon and CNTs in terms of preparation and performance outcome.
An adaptive low‐rank group sparse model based on edge‐preserving for eliminating mixed noise in SRTM
Authors: Fan Xiao , Zhang Hongming , Yang Qinke , Liu Baoyuan , Ge Chenyu , Yan Zhuang , Sun Yuwei , Ni Jincheng , Yuan Linlin , Huang Xiaoxing
Published: September 2024

The Shuttle Radar Topography Mission (SRTM) is a digital representation of the terrain surface morphology that contains rich terrain information and is widely used in environmental analyses. However, SRTM is adversely affected by mixed noise, which typically include random and stripe noise. Mixed noise results in the significant loss of topographic information, which reduce the validity of related research. To eliminate mixed noise in SRTM data, we propose an adaptive low‐rank group sparse model based on edge preservation (ALGS_EP) to remove mixed noise from datasets. The method relies on a low‐rank group sparse model that considers the gradient features of the terrain. It calculates a terrain factor to adapt the noise elimination model to terrain changes. Additionally, it integrates with the edge structure of elevation data and applies a double‐gradient constraint to preserve the structural details of the elevation data. The proposed model, built upon the alternating direction multiplier method framework, enhances the traditional weighted kernel paradigm minimization algorithm by introducing variable weights that adjust according to the gradient of elevation data during iterations. Additionally, it incorporates the correlation between strip noise and residual data blocks when computing the iteration count, ensuring an iterative solution approach that converges to the optimal solution. We used ALGS_EP to process global SRTM 1 data and published a higher‐quality and higher‐precision elevation dataset. The elevation data noise before and after noise elimination were statistically analyzed. Simulated and empirical results show that the model is highly robust and more effective than existing methods in both visual and quantitative evaluations. The noise elimination rate was 97.6%, compared to the original data. Therefore, this research was valuable for applications that use digital elevation model as an important data layer.
Deep Dive Into Churn Prediction in the Banking Sector: The Challenge of Hyperparameter Selection and Imbalanced Learning
Authors: Gkonis Vasileios , Tsakalos Ioannis
Published: September 2024

Forecasting customer churn has long been a major issue in the banking sector because the early identification of customer exit is crucial for the sustainability of banks. However, modeling customer churn is hampered by imbalanced data between classification classes, where the churn class is typically significantly smaller than the no‐churn class. In this study, we examine the performance of deep neural networks for predicting customer churn in the banking sector, while incorporating various resampling techniques to overcome the challenges posed by imbalanced datasets. In this work we propose the utilization of the APTx activation function to enhance our model’s forecasting ability. In addition, we compare the effectiveness of different combinations of activation functions, optimizers, and resampling techniques to identify configurations that yield promising results for predicting customer churn. Our results offer dual insights, enriching the existing literature in the field of hyperparameter selection, imbalanced learning, and churn prediction, while also revealing that APTx can be a promising component in the field of neural networks.
Halide perovskite memristors for optoelectronic memory and computing applications
Authors: Zhang Xiaohan , Wang Yue , Zhao Xiaoning , Wang Zhongqiang , Shan Xuanyu , Xu Haiyang , Liu Yichun
Published: September 2024

Halide perovskites are considered as promising memristive materials for next‐generation optoelectronic devices. This review concisely summarizes the recent development of halide perovskite memristors and highlights their advancements in optoelectronic applications: light‐induced low power switches, optoelectronic logic operations, optoelectronic neuromorphic computation, and artificial vision systems. Finally, we address the challenges and future development prospects of halide perovskites‐based memristors. This review highlights the promising potential of halide perovskite materials for future optoelectronic memory and computing applications.
Impact of accelerated biological aging and genetic variation on esophageal adenocarcinoma: Joint and interaction effect in a prospective cohort
Authors: Zhao Renjia , Yuan Huangbo , Chen Shuaizhou , Xu Kelin , Zhang Tiejun , Liu Zhenqiu , Jiang Yanfeng , Suo Chen , Chen Xingdong
Published: September 2024

Accelerated biological aging may be associated with increased risk of esophageal adenocarcinoma (EAC). However, its relationship with genetic variation, and its effect on improving risk population stratification, remains unknown. We performed an exposome association study to determine potential associated factors associated with EAC. To quantify biological age and its difference from chronological age, we calculated the BioAge10 and Biological Age Acceleration (BioAgeAccel) based on chronological age and nine biomarkers. Multivariable Cox regression models for 362,310 participants from the UK Biobank with a median follow‐up of 13.70 years were performed. We established a weighted polygenic risk score (wPRS) associated with EAC, to assess joint and interaction effects with BioAgeAccel. Four indicators were used to evaluate their interaction effects, and we fitted curves to evaluate the risk stratification ability of BioAgeAccel. Compared with biologically younger participants, those older had higher risk of EAC, with adjusted HR of 1.79 (95%CI: 1.52–2.10). Compared with low wPRS and biologically younger group, the high wPRS and biologically older group had a 4.30‐fold increase in HR (95% CI: 2.78–6.66), at meanwhile, 1.15‐fold relative excess risk was detected (95% CI: 0.30–2.75), and 22% of the overall EAC risk was attributable to the interactive effects (95% CI: 12%–31%). The 10‐year absolute incidence risk indicates that biologically older individuals should begin screening procedures 4.18 years in advance, while youngers can postpone screening by 4.96 years, compared with general population. BioAgeAccel interacted positively with genetic variation and increased risk of EAC, it could serve as a novel indicator for predicting incidence.
A Cascade U‐Net With Transformer for Retinal Multi‐Lesion Segmentation
Authors: Zheng Haiyang , Liu Feng
Published: September 2024

Diabetic retinopathy (DR) is an important cause of blindness. If not diagnosed and treated in a timely manner, it can lead to irreversible vision loss. The diagnosis of DR relies heavily on specialized ophthalmologists. In recent years, with the development of artificial intelligence a number of diagnostics using this technique have begun to appear. One method for diagnosing diseases in this field is to segment four common kinds of lesions from color fundus images, including: exudates (EX), soft exudates (SE), hemorrhages (HE), and microaneurysms (MA). In this paper, we propose a segmentation model for DR based on deep learning. The main part of the model consists of two layers of improved U‐Net network based on transformer, corresponding to the two stages of coarse segmentation and fine segmentation, respectively. The model can segment four common kinds of lesions from the input color fundus image at the same time. To validate the performance of our proposed model, we test our model on three public datasets: IDRiD, DDR, and DIARETDB1. The test results show that our proposed model achieves competitive results compared with the existing methods in terms of PR‐AUC, ROC‐AUC, Dice, and IoU, especially for lesions segmentation of SE and MA.
Remediation strategies for student pharmacists with socio‐behavioral issues in the experiential curriculum: A case series
Authors: Dayer Lindsey , Heldenbrand Seth
Published: September 2024

Background and purpose

This manuscript describes two successful student remediation plans for an introductory pharmacy practice experience (IPPE) and an advanced pharmacy practice experience (APPE). Both students were not successful on rotation due to socio‐behavioral and professionalism deficits.

Educational activity and setting

An IPPE and an APPE remediation student case will be presented in which a student exhibited socio‐behavioral issues in the experiential curriculum that lead to an individual educational plan (IEP) for each student.

Findings

An IPPE student and an APPE student successfully completed an assigned IEP focusing on socio‐behavioral and professionalism remediation and both went on to successfully complete further experiential rotations.

Discussion

There is little guidance in the literature regarding experiential education remediation procedures, especially for students who are unsuccessful due to socio‐behavioral issues (e.g., professionalism, communication, lack of self‐awareness). This paper describes benefits and barriers associated with this type of student educational plan.

A targeted, yet individualized remediation plan including a student assessment and reflection of experiential rotation deficits and presentation to experiential faculty has helped students with a metacognitive understanding of performing better on rotation in the future and allowed for successful completion of future experiential rotations.
Implicit Flow Cytometric Diagnosis of Classic Hodgkin Lymphoma Using CD3+CD4+CD26− T‐Cells
Authors: Gravenmier Curtis , Song Jinming , Shao Haipeng
Published: September 2024

Background

Flow cytometry is not routinely performed in clinical laboratories for the diagnosis of classic Hodgkin lymphoma (CHL).

Methods

Fourteen cases of CHL and 132 cases of the control group were studied by 10‐color flow cytometry, with markers including CD3, CD4, CD7, CD8, and CD26, as well as calculated parameters such as the CD4:CD8 ratio, percent CD3+CD4+CD26− T‐cells of CD3+CD4+ T‐cells, percent CD3+CD4+CD26− T‐cells of total events, CD7 coefficient of variation among CD3+CD4+CD26− T‐cells, and CD7 median fluorescence intensity of CD3+CD4+CD26− T‐cells relative to CD3+CD8+ T‐cells.

Results

CHL cases showed a median percent CD3+CD4+CD26− of CD3+CD4+ T‐cells of 72.3% with range from 41.1% to 94.4%, median percent CD3+CD4+CD26− T‐cells of total events of 17.4% with range from 4.6% to 52.5%, CD7 coefficient of variation among CD3+CD4+CD26− T‐cells less than 100%, and CD7 median fluorescence intensity of CD3+CD4+CD26− T‐cells relative to CD3+CD8+ T‐cells of 1.7 with range from 0.4 to 3.5. In the control group, every entity showed some degree of overlap with CHL in terms of these parameters. A “Hodgkin score” was thus constructed to enhance separation of CHL from other entities. A threshold Hodgkin score of 15.35 achieved a sensitivity of 78.6% and specificity of 96.2% in the diagnosis of CHL. Incorporating the Hodgkin score into a simple algorithm raises the specificity to 100%.

Conclusion

In this study, we used flow cytometry to demonstrate increased CD3+CD4+CD26− T‐cells in CHL, and derived a Hodgkin score for the diagnosis of CHL.
Neuromuscular impairment at different stages of human sarcopenia
Authors: Sarto Fabio , Franchi Martino V. , McPhee Jamie S. , Stashuk Daniel W. , Paganini Matteo , Monti Elena , Rossi Maira , Sirago Giuseppe , Zampieri Sandra , Motanova Evgeniia S. , Valli Giacomo , Moro Tatiana , Paoli Antonio , Bottinelli Roberto , Pellegrino Maria A. , De Vito Giuseppe , Blau Helen M. , Narici Marco V.
Published: September 2024

Background

Degeneration of the motoneuron and neuromuscular junction (NMJ) and loss of motor units (MUs) contribute to age‐related muscle wasting and weakness associated with sarcopenia. However, these features have not been comprehensively investigated in humans. This study aimed to compare neuromuscular system integrity and function at different stages of sarcopenia, with a particular focus on NMJ stability and MU properties.

Methods

We recruited 42 young individuals (Y) (aged 25.98 ± 4.6 years; 57% females) and 88 older individuals (aged 75.9 ± 4.7 years; 55% females). The older group underwent a sarcopenia screening according to the revised guidelines of the European Working Group on Sarcopenia in Older People 2. In all groups, knee extensor muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and MU potential properties by intramuscular electromyography (iEMG). MU number estimate (iMUNE) and blood samples were obtained. Muscle biopsies were collected in a subgroup of 16 Y and 52 older participants.

Results

Thirty‐nine older individuals were non‐sarcopenic (NS), 31 pre‐sarcopenic (PS) and 18 sarcopenic (S). A gradual decrease in quadriceps force, cross‐sectional area and appendicular lean mass was observed across the different stages of sarcopenia (for all P < 0.0001). Handgrip force and the Short Physical Performance Battery score also showed a diminishing trend. iEMG analyses revealed elevated near fibre segment jitter in NS, PS and S compared with Y (Y vs. NS and S: P < 0.0001; Y vs. PS: P = 0.0169), suggestive of age‐related impaired NMJ transmission. Increased C‐terminal agrin fragment (P < 0.0001) and altered caveolin 3 protein expression were consistent with age‐related NMJ instability in all the older groups. The iMUNE was lower in all older groups (P < 0.0001), confirming age‐related loss of MUs. An age‐related increase in MU potential complexity was also observed. These observations were accompanied by increased muscle denervation and axonal damage, evinced by the increase in neural cell adhesion molecule‐positive fibres (Y vs. NS: P < 0.0001; Y vs. S: P = 0.02) and the increase in serum concentration of neurofilament light chain (P < 0.0001), respectively. Notably, most of these MU and NMJ parameters did not differ when comparing older individuals with or without sarcopenia.

Conclusions

Alterations in MU properties, axonal damage, an altered innervation profile and NMJ instability are prominent features of the ageing of the neuromuscular system. These neuromuscular alterations are accompanied by muscle wasting and weakness; however, they appear to precede clinically diagnosed sarcopenia, as they are already detectable in older NS individuals.