bluuebunny/crossref_metadata_2025 huggingface dataset:
CYP3A5 promotes glioblastoma stemness and chemoresistance through fine-tuning NAD+/NADH ratio
Authors: Hu Wentao , Cui Xiaoteng , Liu Hongyu , Li Ze , Chen Xu , Wang Qixue , Zhang Guolu , Wen Er , Lan Jinxin , Chen Junyi , Liu Jialin , Kang Chunsheng , Chen Ling
Published: January 2025

Background

Glioblastoma multiforme (GBM) exhibits a cellular hierarchy with a subpopulation of stem-like cells known as glioblastoma stem cells (GSCs) that drive tumor growth and contribute to treatment resistance. NAD(H) emerges as a crucial factor influencing GSC maintenance through its involvement in diverse biological processes, including mitochondrial fitness and DNA damage repair. However, how GSCs leverage metabolic adaptation to obtain survival advantage remains elusive.

Methods

A multi-step process of machine learning algorithms was implemented to construct the glioma stemness-related score (GScore). Further in silico and patient tissue analyses validated the predictive ability of the GScore and identified a potential target, CYP3A5. Loss-of-function or gain-of-function genetic experiments were performed to assess the impact of CYP3A5 on the self-renewal and chemoresistance of GSCs both in vitro and in vivo. Mechanistic studies were conducted using nontargeted metabolomics, RNA-seq, seahorse, transmission electron microscopy, immunofluorescence, flow cytometry, ChIP‒qPCR, RT‒qPCR, western blotting, etc. The efficacy of pharmacological inhibitors of CYP3A5 was assessed in vivo.

Results

Based on the proposed GScore, we identify a GSC target CYP3A5, which is highly expressed in GSCs and temozolomide (TMZ)-resistant GBM patients. This elevated expression of CYP3A5 is attributed to transcription factor STAT3 activated by EGFR signaling or TMZ treatment. Depletion of CYP3A5 impairs self-renewal and TMZ resistance of GSCs. Mechanistically, CYP3A5 maintains mitochondrial fitness to promote GSC metabolic adaption through the NAD⁺/NADH-SIRT1-PGC1α axis. Additionally, CYP3A5 enhances the activity of NAD-dependent enzyme PARP to augment DNA damage repair. Treatment with CYP3A5 inhibitor alone or together with TMZ effectively suppresses tumor growth in vivo.

Conclusion

Together, this study suggests that GSCs activate STAT3 to upregulate CYP3A5 to fine-tune NAD⁺/NADH for the enhancement of mitochondrial functions and DNA damage repair, thereby fueling tumor stemness and conferring TMZ resistance, respectively. Thus, CYP3A5 represents a promising target for GBM treatment.
Multiparametric MRI and artificial intelligence in predicting and monitoring treatment response in bladder cancer
Authors: Arita Yuki , Kwee Thomas C. , Akin Oguz , Shigeta Keisuke , Paudyal Ramesh , Roest Christian , Ueda Ryo , Lema-Dopico Alfonso , Nalavenkata Sunny , Ruby Lisa , Nissan Noam , Edo Hiromi , Yoshida Soichiro , Shukla-Dave Amita , Schwartz Lawrence H.
Published: January 2025

Bladder cancer is the 10th most common and 13th most deadly cancer worldwide, with urothelial carcinomas being the most common type. Distinguishing between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) is essential due to significant differences in management and prognosis. MRI may play an important diagnostic role in this setting. The Vesical Imaging Reporting and Data System (VI-RADS), a multiparametric MRI (mpMRI)-based consensus reporting platform, allows for standardized preoperative muscle invasion assessment in BCa with proven diagnostic accuracy. However, post-treatment assessment using VI-RADS is challenging because of anatomical changes, especially in the interpretation of the muscle layer.

MRI techniques that provide tumor tissue physiological information, including diffusion-weighted (DW)- and dynamic contrast-enhanced (DCE)-MRI, combined with derived quantitative imaging biomarkers (QIBs), may potentially overcome the limitations of BCa evaluation when predominantly focusing on anatomic changes at MRI, particularly in the therapy response setting. Delta-radiomics, which encompasses the assessment of changes (Δ) in image features extracted from mpMRI data, has the potential to monitor treatment response. In comparison to the current Response Evaluation Criteria in Solid Tumors (RECIST), QIBs and mpMRI-based radiomics, in combination with artificial intelligence (AI)-based image analysis, may potentially allow for earlier identification of therapy-induced tumor changes.

This review provides an update on the potential of QIBs and mpMRI-based radiomics and discusses the future applications of AI in BCa management, particularly in assessing treatment response.

Critical relevance statement

Incorporating mpMRI-based quantitative imaging biomarkers, radiomics, and artificial intelligence into bladder cancer management has the potential to enhance treatment response assessment and prognosis prediction.

Key Points

Quantitative imaging biomarkers (QIBs) from mpMRI and radiomics can outperform RECIST for bladder cancer treatments.

AI improves mpMRI segmentation and enhances radiomics feature extraction effectively.

Predictive models integrate imaging biomarkers and clinical data using AI tools.

Multicenter studies with strict criteria validate radiomics and QIBs clinically.

Consistent mpMRI and AI applications need reliable validation in clinical practice.

Graphical Abstract
Interprofessional collaborative practice in health and social care for people living with multimorbidity: a scoping review protocol
Authors: Murray Josephine-L. K. , Hernandez-Santiago Virginia , Sullivan Frank , Hornal Joanna , Badshah Farhana , Keatley Ben , Galbraith Jillian , Channer Pam , Fearfull Anne , Haddow Anne , Johnston Eleanor , Ward Maureen , O’Carroll Veronica
Published: January 2025

Background

Multimorbidity, the co-existence of two or more conditions within an individual at any one time, is globally increasing and forecasted to rise. This poses a significant challenge for current models of healthcare delivery, which are now ill-equipped to meet the future population health needs. Interprofessional collaborative practice is a specific way professionals work closely together and with patients and their families to improve patient outcomes. Evidence suggests it can improve outcomes for people living with a single condition. What remains unknown is if interprofessional collaborative practice has been used to improve the outcomes of people living with multimorbidity, and if so, to what extent?

Methods

A scoping review is proposed to identify prior peer-reviewed research and grey literature related to interprofessional collaborative practice for multimorbidity in health and social care settings.

A search strategy will identify primary, peer-reviewed research and grey literature. An initial limited search will be conducted to identify relevant existing systematic reviews. Their methods will be examined and their search terms scrutinised. A second comprehensive search will be used to interrogate four databases, looking back 10 years, seeking articles published in English, French, Spanish or Portuguese. Hand searching will be performed on all included full-text articles for any articles missing from the two steps above.

Critical data will be extracted by adapting existing data abstraction forms based on the needs of the research objectives. These forms will be piloted before use.

The results will be analysed descriptively. If appropriate, qualitative content analysis may be undertaken. Where sufficient numbers of homogeneous interventions exist, meta-analysis techniques will be applied.

Results will be presented in tabular, graphic, and diagrammatic information displays.

Discussion

This scoping review will provide an overview of the current evidence base of interprofessional collaborative practice used internationally for people living with multimorbidity in health and social care settings. These findings will provide valuable information to improve health and social care practice as well as change systems and policy to meet the population need of multimorbidity.

Systematic review registration: The protocol was submitted to Open Science Framework on 19 December 2023 and registered on OSF Registries. Registration DOI: https://doi.org/10.17605/OSF.IO/UXHG3.
Spiritual practices as coping with mothers of children with attention-deficit hyperactivity disorder: a qualitative explorative study
Authors: Vithana K. V. G. S. G. , Asurakkody T. A.
Published: January 2025

Background

Mothers of children with ADHD struggle with everyday challenges that exceed from the signs and symptoms of ADHD. They have applied different coping mechanisms, comprising spiritual practice commitments. The study aims to explore spiritual practices as a coping mechanism for mothers of children with ADHD.

Method

Qualitative exploratory research methodology was conducted with 22 mothers who were selected via purposive sampling. Semi-structured interviews were conducted, and the data were analysed via thematic analysis.

Results

The findings were discussed with three main themes and six subthemes:01) cognitive appraisal—thinking with faith and belief about higher power; 2) behavioral practices—individual practices and group approaches; and 3) support from religious leaders—common support with religious concepts and specific personnel support.

Conclusions

This study discussed the religious commitment as coping of mothers, who used them as coping mechanisms while caring for a child with ADHD. They found a variety of culturally bound religious practice methods that were reported to be perceived as effective for their mental well-being.
Mechanosensor YAP mediates bone remodeling via NF-κB p65 induced osteoclastogenesis during orthodontic tooth movement
Authors: Deng Jie , Zhang Yu-Ning , Bai Ru-Shui , Yu Ting-Ting , Zhao Yi , Liu Hao , Zhang Yun-Fan , Xu Tian-Min , Han Bing
Published: January 2025

Background

Yes-associated protein (YAP) is a crucial mechanosensor involved in mechanotransduction, but its role in regulating mechanical force-induced bone remodeling during orthodontic tooth movement (OTM) is unclear. This study aims to elucidate the relationship between mechanotransduction and mechanical force-induced alveolar bone remodeling during OTM.

Results

Our study confirms an asynchronous (temporal and spatial sequence) remodeling pattern of the alveolar bone under mechanical force during OTM. Both compression and tension activate osteoclasts recruiting to the alveolar bone, whereas no significant presence of osteoblasts in the alveolar bone at the early stages of bone remodeling. Specifically, applying different force magnitudes (10, 25, 50, 100 g) to rats’ 1st molars affected OTM distance. Force-induced alveolar bone remodeling was characterized by osteoclastogenesis and YAP activation at compressive/tensile sites on day 1 of OTM. Notably, 25 g force triggered peak YAP expression and osteoclastic activity early on. Time-course analysis revealed two YAP activity peaks on day1 and 14, contrasting with one peak of type I collagen expression on day14. In addition, RNA-sequencing highlighted increased nuclear factor kappa B (NF-κB) signaling, mineral absorption, and osteoclast differentiation at day-1 and 3. Moreover, gene expression analysis showed similar trends for NF-κB p65, YAP1, and TEA domain 1 (TEAD1) during this time. Furthermore, experiments on osteoclast cultures indicated YAP activation via large tumor suppressor (LATS) and TEAD under mechanical stimuli (compression/tension), promoting osteoclastogenesis by regulating NF-κB p65 and receptor activator of NF-κB (RANK). Inhibiting YAP with verteporfin delayed OTM by impairing force-induced osteoclastic activities in vivo and ex-vivo.

Conclusions

We propose that YAP mediates alveolar bone remodeling through NF-κB p65-induced osteoclastogenesis in an asynchronous remodeling pattern during OTM. Both compression and tension activate osteoclasts recruiting to the alveolar bone at early stages of bone remodeling, offering evidence for orthodontists as a reference.
Parametric analysis on the transient two-phase wellbore model applied to the Yangyi high-temperature geothermal field
Authors: Chen Chaofan , Zhou Hongwei , Nagel Thomas , Renaud Theo , Naumov Dmitri , Kolditz Olaf , Shao Haibing
Published: January 2025

Purpose

In high-temperature geothermal fields, interpretation of the dynamic two-phase state inside the production wells under different wellhead conditions are important to effectively use the geothermal heat source. Therefore, the corresponding wellbore models must have the capability to simulate transient flow and energy state in geothermal wellbores, as well as advective and conductive heat and mass interactions with surrounding formation.

Methods

In this study, a transient two-phase wellbore model is developed and implemented in the open source software OpenGeoSys, to simulate both flow and energy state in the wellbore, as well as advective and conductive heat and mass interactions with surrounding formation. The model is first verified against analytical solutions and numerical results from the open-source simulator FloWell. The model is then further validated with well logging data from the Yangyi geothermal field in Tibet, China.

Results

Based on the simulation results of the parametric analysis, the conductive heat loss of the high-velocity geothermal production well in the Yangyi geothermal field is found to be limited and the influence can be safely neglected after 8 h of discharge. The flash point location in the wellbore moves upwards for 112 m along with the decrease in fluid enthalpy by 200 kJ/kg. In the wellbore shut-in process, the wellhead pressure decreases with decreasing velocity, while the location of the flash point does not change much. After wellbore shut-in, a two-phase state still exists in the closed wellbore, and the temperature profile is dominated by conductive heat exchange with the surrounding formation. Taking into account the impact of the feed zone, the mass flow rate of the ZK203 well in the Yangyi geothermal field increases from 122.87 to 126.26 t/h when the wellhead pressure decreases from 1.26 to 1.18 MPa.

Conclusion

The open-source two-phase wellbore model developed and implemented in this work provides preliminary insights into the transition and evolution of the two-phase state in high-temperature production wells considering advective and conductive interactions with the surrounding formation.
Advancing hospital healthcare: achieving IoT-based secure health monitoring through multilayer machine learning
Authors: Qi Ke
Published: January 2025

Background

Data based clinical decision support system is a boon for health care monitoring. Smart healthcare monitoring systems play a vital role in the early diagnosis and detection of the physical and mental health of patients. The smart clinical IoT (C-IoT) systems are data-driven and provide efficient support for this purpose.

Purpose

There is a need to have a secure, accurate, and efficient HCM system that is capable of processing large amounts of patient data for timely diagnosis and detection of various health complications. Traditional ways of migration are imprecise, less secure, and do not cover all angles necessary in the contemporary healthcare environment. Because of this, the conceptual IoT-based secure health monitoring system employs machine learning algorithms for enhanced accuracy.

Method

This study presents the conjugate applications of machine learning algorithms with the cloud-based C-IoT model systems. This model is a lightweight encryption block model that maintains provisional security for health and clinical data. It assists in patient’s health issues which are diagnosed with the existing database of the history of that patient and proper measures are taken with proper diagnosis and using this prediction model. The health status is diagnosed from the pre-historical database of the patient’s database.

Results

This cloud-based smart C-IoT system shows the results approximately with 91% accuracy while using Artificial Neural Network (ANN) algorithms. This smart C-IoT-based health issue diagnostic model is one step ahead toward the modernization of society 5.0.

Future prospects

The proposed IoT-based secure health monitoring system expands the surgeries of health care by achieving a high diagnostic accuracy of 91% employing ANN algorithms, the excellence of which is founded on data intensity with prior patient data, and the data security by lightweight encryption algorithms. Aligned with Society 5.0, it brings new, friendly, and efficient features to healthcare that replace many existing methods with better ones in terms of precision, security, and coverage.
Spatiotemporal variations in integrated trophic positions of stream macroinvertebrate communities
Authors: Ishikawa Naoto F. , Uehara Yoshitoshi , Ishida Takuya , Ikeya Tohru , Asano Satoshi , Ko Chia-Ying , Iwata Tomoya , Tayasu Ichiro , Ohkouchi Naohiko , Okuda Noboru
Published: January 2025

To understand energy and material cycles on surface Earth, it is important yet challenging to estimate trophic transfer through ecosystems. To address this issue, the integrated trophic position (iTP), defined as a biomass-weighted average TP of a given food web, is useful because the iTP can be a proxy for the configuration of ecological pyramid. Here we conducted the compound-specific nitrogen isotope analysis of amino acids for macroinvertebrate communities collected from the Ado and Yasu Rivers in the Lake Biwa watershed, Japan, to estimate their iTP values. Unlike previous studies, no clear relationships between iTP and biodiversity (Shannon index H’) were found. However, by comparing the irrigated period and the non-irrigated period within the Yasu River, the decrease in iTP values was fairly characterized by the increase in H’. A significant difference in the observed iTP values compared to those reported in the previous study suggests that the configuration of ecological pyramid in stream ecosystems is dynamic rather than static. We also found that the iTP values of stream macroinvertebrate communities (2.37 ± 0.24) (n = 43), marine mesozooplankton communities (2.33 ± 0.34) (n = 14), and animal communities with various taxonomic groups (2.42 ± 0.21) (n = 158) are all comparable with each other, suggesting that partial communities involving macroinvertebrates well represent the configuration of total ecological pyramid. This finding clearly delineates the promising performance of the iTP index for the trophic transfer of energy, which should be further explored in a variety of ecosystems.
Forecasting stock returns: the role of VIX-based upper and lower shadow of Japanese candlestick
Authors: Dai Zhifeng , Zhu Haoyang , Chang Xiaoming , Wen Fenghua
Published: January 2025

This paper proposes a new predictor by calculating the difference between the Japanese candlestick’s upper and lower shadows (ULD) constructed from CBOE volatility index (VIX) data. ULD is a powerful predictor for future stock returns, and higher ULD leads to the subsequent decline of stock returns. Our results show that our new predictor generates R^2 values of up to 2.531% and 3.988% in-sample and out-of-sample, respectively; these values are much larger than the previous fundamental predictors. Moreover, the predictive information contained in ULD can help mean–variance investors achieve certainty equivalent return gains of as high as 327.1 basis points. Finally, the extension analysis and robustness tests indicate that recession is the primary cause of return predictability; our results are robust under different settings.
Revisiting the role of education in attitudes toward immigration in different contexts in Europe
Authors: Umansky Karen , Weber Daniela , Lutz Wolfgang
Published: January 2025

Among the individual determinants of attitudes toward immigration, the liberalising role of education is well known—those with higher levels of education tend to be more in favour of immigration. However, recent socioeconomic changes and idiosyncratic differences between European countries prompt us to reassess the role of education, given these contextual differences. Does it still apply, and is it universal? Moreover, does this relationship apply to both cultural and economic attitudes toward immigration? Using data from the European Social Survey, we analyse the role of education and socioeconomic changes in shaping economic and cultural attitudes toward immigration in 15 European countries over 16 years using a hierarchical model with cross-classified random effects. In our analysis, we distinguish between Eastern European and non-Eastern European countries. Our results indicate a robust positive and significant association between higher levels of education and more tolerant attitudes toward immigration in both aspects. However, they also reveal that the strength of this relationship varies between the two attitudes by context and region. For example, higher migrant inflow rates attenuate education’s liberalising and empowering role in shaping cultural attitudes in non-Eastern European countries but are not significant in Eastern European countries. Thus, our findings contribute to the literature examining the role of context in the established relationship between education and immigration attitudes while providing insights into regional differences.
Comparison of CT-like MRI sequences for preoperative planning of cochlear implantation using super-high-resolution CT as a reference
Authors: Puel Ulysse , Beysang Achille , Hossu Gabriella , Eliezer Michael , Assabah Bouchra , Ambarki Khalid , Gondim Teixeira Pedro Augusto , Blum Alain , Parietti-Winkler Cécile , Gillet Romain
Published: January 2025

Background

We evaluated the accuracy of magnetic resonance imaging (MRI) computed tomography (CT)-like sequences compared to normal-resolution CT (NR-CT) and super-high-resolution CT (SHR-CT) for planning of cochlear implantation.

Methods

Six cadaveric temporal bone specimens were used. 3-T MRI scans were performed using radial volumetric interpolated breath-hold (STARVIBE), pointwise-encoding time reduction with radial acquisition (PETRA), and ultrashort time of echo (UTE) sequences. CT scans were performed on two scanners for SHR-CT and NR-CT acquisitions. Two radiologists evaluated accuracy based on preimplantation metrics and the ability to identify various anatomical structures, particularly the facial recess and round window. Wilcoxon rank-sum test and intraclass correlation coefficient (ICC) were used.

Results

The facial nerve was always clearly visible (score ≥ 2) in the MRI, NR-CT, and SHR-CT scans (p ≥ 0.621). However, the chorda tympani nerve (CTN) was clearly visualized in UTE, STARVIBE, and PETRA sequences in only 33% (2/6 specimens, p = 0.016), 50% (3/6 specimens, p = 0.038), and 83% (5/6 specimens, p = 0.017) of cases, respectively, whereas it was always clearly visualized in SHR and NR-CT (p = 0.426). The round window (RW) was never visualized in MRI sequences (p ≤ 0.010), whereas it was identified in all cases in SHR and NR-CT (p = 1.000). There was a strong correlation between measurements obtained from MRI and CT modalities (ICC ≥ 0.837).

Conclusion

MRI CT-like sequences assessed the facial nerve in all cases and the CTN in up to 87% of cases. However, the detection of the RW was insufficient for surgical planning. CT and MRI measurements were in agreement.

Relevance statement

CT-like MRI sequences can image the anatomy of the facial recess and the length of the basal turn of the cochlea with similar accuracy as conventional CT, although they cannot image the round window.

Key Points

CT-like MRI sequences are not widely used in preoperative cochlear implantation imaging.

CT-like sequences can image the facial recess as well as conventional CT.

CT-like sequences can image the basal turn length of the cochlea as well as conventional CT.

Round window depiction is not possible with CT-like MRI sequences.

Graphical Abstract
Higher severity fire increases the long-term competitiveness of pyrophytes in an upland oak-pine forest, Kentucky, USA
Authors: Culbert Scott G. , Arthur Mary A. , Cotton Claudia A. , Muller Jacob J.
Published: January 2025

Background

In eastern North American forests and woodlands, formerly dominant oaks (Quercus spp. L.) and pines (Pinus spp. L.) are experiencing widespread regeneration challenges. These challenges are due to past land use and fire exclusion facilitating positive feedbacks that reduce the effectiveness of low-severity prescribed fire. High-severity fires (wildfires and potentially prescribed burns) offer promise to overcome these feedbacks and assist in ecosystem restoration. In 2010, a 670-ha mixed-severity wildfire burned in the Daniel Boone National Forest, Kentucky, USA, providing a rare opportunity to track oak-pine community recovery across a wide fire severity spectrum for 12 years. We examined the effects of burn severity on species diversity, forest structure, community assemblage, stem recruitment into the midstory (2–10 cm diameter at breast height [DBH]) and canopy (10 + cm DBH), and non-native invasive plant (NNIP) populations, and compared these effects to previous results published after 6 years post-fire.

Results

The relative importance of midstory pyrophyte species (e.g., Quercus spp. and Pinus spp.) was positively related to field-measured burn severity, while mesophytes (e.g., Acer rubrum, Betula lenta) displayed a weaker negative relationship. After 12 years, higher burn severity yielded greater midstory recruitment of pyrophytes; however, this was only observed for yellow pines (P. echinata Mill., P. rigida Mill., P. virginiana Mill.) and non-oak-pine pyrophytes. Oaks’ and mesophytes’ midstory recruitment displayed no relationship with burn severity. Increased burn severity strongly increased invasive species presence, particularly Chinese silvergrass (Miscanthus sinensis Andersson).

Conclusions

Six years after fire, oak midstory recruitment was positively related to burn severity. By year 12, higher burn severity was no longer associated with oak midstory recruitment but was associated with increased recruitment and importance of other pyrophytic species, particularly yellow pines. Our results also suggest that a single high-severity fire can increase the long-term competitive status of pyrophytes relative to mesophytes. As such, higher-severity fire may be an important tool in restoring fire-adapted communities where low-severity fire lacks the ability to produce meaningful forest structure and community changes. However, NNIP proliferation in high-severity burn areas can undermine the restoration benefits we observed.
Super Absorbent Polymers (SAPs) as concentration preservers in brine deicers for enhanced ice melting capacity
Authors: Merke Gage , Hesami Maedeh , Kiran Ravi
Published: January 2025

Rock salt brine deicers are among the most prevalent solutions for ensuring safe vehicle operation in snow-prone regions. The efficiency of this solution, however, decreases at extremely low temperatures as it is diluted by melted ice. The objectives of the current study are: 1) to enhance the ice melting capacity of salt brine at extremely low temperatures (0 °C, − 10 °C, − 20 °C, and − 30 °C) using super absorbent polymers (SAPs), and 2) to measure the reduction in the skid resistance of pavements when the SAP-brine solutions are applied on the surface. Five commercially available SAPs are explored for their potential to maintain concentration during the ice melting process. Three weight fractions of SAPs are introduced into traditional sodium chloride (NaCl) brine: 5% by weight replacement of NaCl along with 5% and 10% addition of SAPs in salt brine solution. The experimental work includes quantifying swell rates and capacities of each SAP in saline solution employing a tea-bag method, measuring the ice melting capacity of brines with SAP additives using an in-house ice melting test setup, and assessing reduction in skid resistance employing British Pendulum tester. The results showed that the addition of 5% large particle-sized SAPs enhanced the ice melting capacity by up to 80% compared to the brine solution at − 30°C. Such improvement in ice melting capacity occurred by preserving the salt concentration in the SAP absorbed water. Moreover, the results of the skid resistance test revealed a negligible reduction in skid resistance (up to 2% compared with dry pavement) when 5% large-sized SAP-brine solutions are applied on both Portland Cement Concrete and asphalt pavements.
Ameliorative effect of curcuminoids in liver fibrosis rat model via regulating GIPC1 gene and modulating MMP-8/TIMP-3 balance mediated by miR-483-5p
Authors: Adel Rana Mostafa , Kamal Sara Mostafa , Sherif Eman Adel , El-shafiey Sara Hatem
Published: January 2025

Background

Liver fibrosis is a worldwide disease that develops from activation and propagation of hepatic stellate cells, and subsequent extracellular matrix accumulation. Liver fibrosis is associated with multiple pathways, however, the dysregulation of GIPC1 gene (GIPC PDZ domain containing family member 1) and disruption in the balance of MMPs (matrix metalloproteinases) and TIMPs (tissue inhibitor of metalloproteinases) remain as key factors in this disease. Curcuminoids, especially curcumin (CURC), are medicinal extracts that proved their antioxidative, anti-inflammatory, antifibrotic actions, and showed wide epigenetic regulatory effects. We aimed to explore CURC’s effect on declining the inflammatory cytokines TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin-6), TGF-β1 (transforming growth factor beta1), regulating GIPC1 expression, and adjusting MMP-8/TIMP-3 balance mediated by miRNA-483-5p (microRNA-483-5p) in TAA (thioacetamide)-induced liver fibrotic albino Wistar rat model.

Results

The attained results revealed significant regressions in livers’ relative weights, serum ALT (alanine aminotransferase), AST (aspartate aminotransferase), ALP (alkaline phosphatase) and LDH (lactate dehydrogenase), plasma PDGF (platelet-derived growth factor), liver TOC (total oxidative capacity), TNF-α, IL-6, TGF-β1, and downregulation in GIPC1 gene expression, besides, significant elevation in liver TAC (total antioxidant capacity) in CURC-treated rats. Surprisingly, significant upregulation in miRNA-483 expression was obtained in CURC-treated rats which consequentially enhanced MMP-8/TIMP-3 balance in the form of an elevation in MMP-8/reduction in TIMP-3 levels, along with confirming this novel pathway through conducting bioinformatics analysis. All these enhancements were mirrored in Annexin V/PI (Annexin V Propidium Iodide) assay as massive improvements in % of apoptotic and necrotic cells, plus, in H&E (hematoxylin and eosin) and Masson’s trichrome histopathological examinations that showed near to normal liver architecture with no collagen bands deposition.

Conclusions

This study concludes that CURC can modulate the novel miRNA-483-5p/MMP-8/TIMP-3 pathway and regulate GIPC1 expression, thus providing new perception of CURC as an effective therapeutic agent capable of lowering inflammation and remodeling liver damage.

Graphical Abstract
Long-Term Persistence of Glycemic Dysregulation in Patients With a History of Pheochromocytoma/Paraganglioma
Authors: Fischer Alessa , Remde Hanna , Pamporaki Christina , Dischinger Ulrich , Bechmann Nicole , Robledo Mercedes , Wang Katharina , Vetter Diana , Oberholzer José , Morand Grégoire B , Mueller Simon Andreas , Huber Alexander , Fritsch Ralph , Gruber Sven , Hantel Constanze , Zitzmann Kathrin , Reincke Martin , Auernhammer Christoph J , Pacak Karel , Grossman Ashley B , Beuschlein Felix , Nölting Svenja
Published: January 2025

Context

Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors that frequently produce catecholamines. Catecholamine-induced cardiometabolic complications substantially contribute to increased morbidity and mortality in PPGL patients prior to surgical resection.

Objective

To determine whether markers of elevated cardiometabolic risk persist in patients following PPGL resection.

Methods

In this retrospective analysis of a multicenter cohort of patients with PPGLs participating in the prospective ProsPheo study and the ENS@T registry, cardiometabolic risk factors, including glycemic status, dyslipidemia, and body mass index (BMI), were assessed in patients with PPGL at diagnosis and during follow-up. Patients with a history of resected PPGL were compared to a control group with nonfunctioning adrenal adenomas from the ENS@T registry.

Results

Patients with a present PPGL or a history of PPGL (n = 188), a metastatic PPGL (n = 27), or a known susceptibility gene pathogenic variant (PV) for the development of PPGL without a history of PPGL (n = 44) were included. We compared the asymptomatic PV carriers to patients with a history of PPGL: those with a history of PPGL showed a significantly higher prevalence of hyperglycemic disorders (P = .013) compared with asymptomatic PV carriers. In patients with a history of PPGL and at least 12 months of follow-up post surgery (n = 113), the prevalence of hyperglycemic disorders (P < .001), as well as the mean HbA1c (5.63%, SD 0.43%), were significantly higher, compared to a control group with nonfunctioning adrenal adenomas (n = 76) of similar age and BMI (HbA1c 5.45%, SD 0.40%; P = .004).

Conclusion

Glycemic disturbances persist long-term after the resection of PPGL.
Abnormal Glucagon Secretion Contributes to a Longitudinal Decline in Glucose Tolerance
Authors: Mohan Sneha , Christie Hannah E , Laurenti Marcello C , Egan Aoife M , Bailey Kent R , Cobelli Claudio , Dalla Man Chiara , Vella Adrian
Published: January 2025

Context

Defects in insulin secretion and action contribute to the progression of prediabetes to diabetes. However, the contribution of α-cell dysfunction to this process has been unclear.

Objective

This work aimed to understand the relative contributions of α-cell and β-cell dysfunction to declining glucose tolerance.

Methods

A longitudinal, community-based observational study was conducted at a clinical research unit at an academic medical center. We studied 96 individuals without diabetes (age 55 ± 1 years; body mass index 27.7 ± 0.4) on 2 occasions, 3 years apart using an oral 75-g glucose challenge. Indices for insulin secretion and action were estimated using the oral minimal model. Glucagon secretion rate (GSR) was estimated by deconvolution from peripheral glucagon concentrations. Main outcome measures included glucose tolerance status (categorical variable) and then symmetrical percentage change in peak and 120-minute glucose (post oral glucose tolerance test) concentrations (continuous variables).

Results

A total of 32 individuals progressed from normal to impaired glucose tolerance (IGT) or from IGT to type 2 diabetes. The disposition index (DI) declined in the progressors (568 ± 98 vs 403 ± 65 10−4 dL/kg/min per μU/mL, baseline vs 3 years; P = .04). α-Cell suppression by glucose (δGSR/δglucose) did not change in the nonprogressors (1.5 ± 0.1 vs 1.3 ± 0.1 nmol/min/L; P = .37) but decreased (1.0 ± 0.2 vs 0.8 ± 0.2 nmol/min/L; P < .01) in those who progressed. Analysis of the entire cohort showed that DI and δGSR/δglucose were independently and inversely correlated with an increase in glycemic excursion.

Conclusion

These data show that α-cell dysfunction accompanies a decline in β-cell function as IGT or overt type 2 diabetes develops.
Regional Anesthesia Management in a Fontan Patient Presenting for Ambulatory Shoulder Surgery: A Case Report
Authors: Ranganath Yatish S. , Chung Eric , Carmony Megan , Mazurek Michael
Published: January 2025

Interscalene blocks, commonly used for shoulder surgery analgesia, often cause transient phrenic nerve palsy, leading to hemi-diaphragmatic paresis. This complication is particularly problematic in patients with pulmonary comorbidities and has been extensively investigated. However, its impact on patients with Fontan physiology remains less understood with limited representation in the literature. Hemi-diaphragmatic paresis can significantly reduce negative pressure spontaneous ventilation, leading to decreased venous return and increased pulmonary vascular resistance, which critically affects cardiac output. This case report explores regional anesthesia management in a Fontan patient undergoing shoulder surgery, emphasizing the suprascapular nerve block as an effective alternative for ambulatory patients.
Regulation of MAP2, GFAP, and calcium in the CA3 Region Following Kainic Acid Exposure to organotypic hippocampal slice culture
Authors: Husna Machlusil , Handono Kusworini , Sujuti Hidayat , Aulanni'am Aulanni'am , Rukmigarsari Ettie
Published: January 2025

Background Neurodegeneration due to neurotoxicity is one of the phenomena in temporal lobe epilepsy. Experimentally, hippocampal excitotoxicity process can occur due to kainic acid exposure, especially in the CA3 area. Neuronal death, astrocyte reactivity and increased calcium also occur in hippocampal excitotoxicity, but few studies have investigated immediate effect after kainic acid exposure. The organotypic hippocampal slice culture (OHSC) is a useful model for studying the neurodegeneration process, but there are still many protocol differences. In this study, minor modifications were made in the OHSC protocol. Methods OHSC was obtained from three healthy wild type Wistar rats aged P10. Healthy culture slices were obtained and lasted up to 10 days in vitro (DIV 10). Bath application of kainic acid for 48 hours in DIV 10 followed by observation of its initial effects on neurons, astrocytes, and calcium via the expression of MAP2, GFAP, and intracellular calcium imaging, subsequently. Results After 48 h of kainic acid administration, there was a significant increase in intracellular calcium intensity (p = 0.006 < α), accompanied by a significant decrease in MAP2 (p = 0.003 < α) and GFAP (p = 0.010 < α) expression. Conclusion These findings suggest early neuronal and astrocyte damage at the initial onset of hippocampal injury. This implies that astrocyte damage occurs early before an increase in GFAP that characterizes reactive astrogliosis found in other studies. Damage to neurons and astrocytes may be associated with increased intracellular calcium. It is necessary to develop further research regarding regulation of calcium, MAP2, and GFAP at a spatial time after exposure to kainic acid and strategies to reduce damage caused by excitotoxicity.
Computational Study Protocol: Leveraging Synthetic Data to Validate a Benchmark Study for Differential Abundance Tests for 16S Microbiome Sequencing Data
Authors: Kohnert Eva , Kreutz Clemens
Published: January 2025

Background Synthetic data’s utility in benchmark studies depends on its ability to closely mimic real-world conditions and reproduce results obtained from experimental data. Building on Nearing et al.’s study (1), who assessed 14 differential abundance tests using 38 experimental 16S rRNA datasets in a case-control design, we are generating synthetic datasets that mimic the experimental data to verify their findings. We will employ statistical tests to rigorously assess the similarity between synthetic and experimental data and to validate the conclusions on the performance of these tests drawn by Nearing et al. (1). This protocol adheres to the SPIRIT guidelines, demonstrating how established reporting frameworks can support robust, transparent, and unbiased study planning. Methods We replicate Nearing et al.’s (1) methodology, incorporating synthetic data simulated using two distinct tools, mirroring the 38 experimental datasets. Equivalence tests will be conducted on a non-redundant subset of 46 data characteristics comparing synthetic and experimental data, complemented by principal component analysis for overall similarity assessment. The 14 differential abundance tests will be applied to synthetic and experimental datasets, evaluating the consistency of significant feature identification and the number of significant features per tool. Correlation analysis and multiple regression will explore how differences between synthetic and experimental data characteristics may affect the results. Conclusions Synthetic data enables the validation of findings through controlled experiments. We assess how well synthetic data replicates experimental data, try to validate previous findings with the most recent versions of the DA methods and delineate the strengths and limitations of synthetic data in benchmark studies. Moreover, to our knowledge this is the first computational benchmark study to systematically incorporate synthetic data for validating differential abundance methods while strictly adhering to a pre-specified study protocol following SPIRIT guidelines, contributing to transparency, reproducibility, and unbiased research.
Nieformalna edukacja dorosłych dla dobra dziecka na przykładzie społeczności poznańskich „Łejerów” .
Authors: Sadowska Katarzyna
Published: January 2025

Celem niniejszego opracowania jest ukazanie wybranych problemów nieformalnej edukacji dorosłych na przykładzie istniejącej już niemalże 50 lat poznańskiej pedagogiki „łejerskiej” skoncentrowanej na potrzebach dziecka. Za edukację nieformalną dorosłych przyjmuje się proces uczenia się osób dorosłych dokonujący się przede wszystkim w sposób nieformalny i przebiegający w naturalnych warunkach ich codziennej aktywności. Wśród technik badawczych zastosowanych w procesie odpowiedzi na pytanie badawcze: „Jak przebiega nieformalna edukacja dorosłych w aspekcie uwrażliwienia ich na potrzeby dziecka (na przykładzie „łejerskiej” pedagogiki i „łejerskiej” społeczności)?”, zastosowano analizę źródeł zastanych (opracowań, komunikatów prasowych, materiałów prywatnych Jerzego Hamerskiego oraz stron internetowych powiązanych z „Łejerami”) i źródeł wywołanych, w tym wywiadów realizowanych w roku szkolnym 2023/ 2024 przez autorkę z Jerzym Hamerskim – założycielem „Łejerów”. Zastosowano ponadto obserwację uczestniczącą – autorka w roku szkolnym 2023/2024 brała udział w wydarzeniach społeczności Szkoły Podstawowej nr 83 w Poznaniu. Badania umiejscowione zostały w paradygmacie badań jakościowych. Pedagodzy „łejerscy” od początku swojej działalności wpisują się w koncepcję „nowego dziecka” akcentując na każdym kroku postulat poznawania dzieciństwa i dziecka poprzez zrozumienie dziecięcej percepcji świata. Celem pedagogów „łejerskich” jest więc nie tylko upowszechnianie konstruktu „nowego dziecka”, ale i edukacja dorosłych osób w zakresie potrzeb, możliwości i problemów nurtujących młodych ludzi.
Kształcenie osób skazanych w szkołach i placówkach poza instytucją penitencjarną. Ujęcie ilościowe
Authors: Jarzębińska Aneta
Published: January 2025

CEL NAUKOWY:
Celem artykułu jest analiza liczby osadzonych, którzy po 1997 roku uczęszczali do szkół i innych placówek kształcenia na wolności w kontekście ogólnej liczby osadzonych słuchaczy i osadzonych uczestników kursów.
PROBLEM i METODY BADAWCZE:
Pierwszy problem badawczy dotyczył określenia ogólnej liczby osadzonych – słuchaczy szkół. Formułując drugi problem zamierzano ustalić, jaki udział w ogólnej liczbie słuchaczy mieli ci, którzy uczęszczali do szkół na wolności. Podobny schemat miały dwa kolejne problemy a odnoszące się do liczby osadzonych uczestniczących w kursach. Piąty z problemów badawczych dotyczył liczby osadzonych, którzy kształcąc się korzystali z przepustek w celu konsultacji lub zdania egzaminów. Badanie przeprowadzono z zastosowaniem metody analizy danych zastanych. Danymi były natomiast: a) opracowane przez Służbę Więzienną analizy wyników dydaktyczno-resocjalizacyjnych uzyskanych przez szkoły funkcjonujące w zakładach karnych i aresztach śledczych za lata szkolne od 1999/2000 do 2022/2023; b) opracowane przez Ministerstwo Sprawiedliwości oraz Służbę Więzienną informacje o wykonywaniu kary pozbawienia wolności i tymczasowego aresztowania, począwszy od 1999 roku.
WYNIKI ANALIZY NAUKOWEJ:
W kilku ostatnich latach osób osadzonych, które uczestniczyły w formalnym kształceniu na wolności, było zdecydowanie mniej, niż wcześniej i mniejszy był ich udział w ogólnej liczbie osadzonych słuchaczy czy uczestników kursów. Spostrzeżenie dotyczy zwłaszcza słuchaczy szkół systemu oświaty poza jednostkami penitencjarnymi i studiujących. 
WNIOSKI, REKOMENDACJE I APLIKACYJNE ZNACZENIE WPŁYWU BADAŃ:
Ze względu na wskazane w artykule unikatowe walory kształcenia osób osadzonych na wolności warto to rozwiązanie propagować. Jednak należy tworzyć warunki dla jego wdrażania, głównie przygotowując społeczeństwo w toku edukacji do zrozumienia potrzeb osób niedostosowanych.
Wykład inauguracyjny Johanna Philippa Breyne’a w gdańskiej Societas Litteraria
Authors: Pękacka-Falkowska Katarzyna
Published: January 2025

Pierwszym prywatnym towarzystwem naukowym w Gdańsku była założona w 1720 r. Societas Litteraria Cuius Symbolum Virtutis et Scientiarum Incrementa. Stowarzyszenie, początkowo nakierowane na humaniora, zmieniło swój profil badawczy w 1721 r. po przyjęciu do grona członków doktora filozofii i medycyny Johanna Philippa Breyne’a. W wykładzie inauguracyjnym o charakterze manifestu programowego uczony wytyczył na kolejne sześć lat główne kierunki rozwoju towarzystwa, przesuwając główny ciężar jego zainteresowań z historii i prawa na przyrodoznawstwo. W artykule zarysowano wybrane okoliczności udanych i nieudanych prób powoływania towarzystw naukowych w Gdańsku do 1720 r. oraz zaprezentowano treść inauguracyjnego wykładu J.P. Breyne’a z 1721 r.
The Impact of Intermittent Fasting: Enhancing Health and Mitigating Disease Risks
Authors: Grzelak Alicja
Published: January 2025

Introduction: Intermittent fasting (IF) has emerged as a popular dietary intervention for its potential health benefits, including weight management, metabolic improvement, and reduced risk of chronic diseases. The practice alternates periods of eating and fasting, influencing physiological processes and offering an alternative to traditional calorie-restrictive diets.
Purpose of Work: This paper aims to investigate the efficacy of IF as a revolutionary approach to maintaining health and mitigating the risks associated with chronic diseases. By analyzing contemporary research, the paper seeks to elucidate the underlying mechanisms and broader health implications of IF.
State of Knowledge: Existing studies suggest that IF positively affects metabolic markers, enhances insulin sensitivity, and promotes autophagy—a cellular repair mechanism crucial for longevity and disease prevention. Emerging evidence links IF to improved cardiovascular health, reduced inflammation, and enhanced cognitive functions. However, variability in outcomes due to age, gender, and fasting protocols highlights the need for tailored approaches and further research.
Material and methods: The research methodology entailed establishing the study aims, undertaking a systematic review of the literature, and implementing a structured process to screen pertinent studies. The investigation involved a comprehensive search across scientific databases, including PubMed and Google Scholar.
Summary: Intermittent fasting represents a transformative paradigm in health and nutrition science. While preliminary findings are promising, more robust longitudinal studies are required to establish standardized protocols and validate its therapeutic potential across diverse populations. This paper underscores the promise of IF as a strategic tool in the prevention and management of chronic diseases.