bluuebunny/crossref_metadata_2025 huggingface dataset:
Exact critical temperatures for snap-through of an active simply supported buckled beam under a longitudinal half sine wave temperature profile
Authors: Smith Matthew L
Published: February 2025

The buckled beam is a fundamental building block used to produce morphing structures. The advancement of responsive materials has enabled these building blocks to actively transform structures between multiple states. Often the driving stimulus is applied to these structural elements in a longitudinally nonuniform fashion. However, most models assume uniform application of the stimulus or rely on numerical results, which obscure connections between the system parameters and the system response. In this work, we examine a thermally responsive, buckled beam and consider the temperature profile to be a half sine wave along its length. This assumption makes the analysis convenient and enables the derivation of an exact expression for the critical temperature rise leading to loss of stability under a range of conditions. In addition, a very simple expression is obtained for predicting the crossover from the symmetric snap-through mode to unsymmetrical transitions between buckled states. The results give insight into system design strategies and also lay the foundation for analyzing more complex systems.
Capital cities in multi-level settings: Assessing Scottish and Welsh residents’ perceptions of London, Edinburgh and Cardiff
Authors: Vampa Davide
Published: February 2025

Devolution processes, while aiming to transfer power to sub-state entities, contribute to creating new political, administrative, and economic centres. Consequently, in multi-level systems, we observe the coexistence of state-wide and sub-state capital cities, which may be perceived differently by citizens. This article focuses on the United Kingdom and analyses the results of an original survey conducted in Scotland and Wales. In these two devolved nations, sub-state capital cities, Edinburgh and Cardiff, ‘compete’ with the UK capital, London. Respondents were asked to assess these three cities across three dimensions: the individual/value dimension, the symbolic dimension, and the integrative dimension. While, overall, both Edinburgh and Cardiff outperform London on all three dimensions, important differences exist among respondents. This study shows that far from being neutral, the role of capital cities in devolved jurisdictions can be highly politicised and is also closely associated with individual preferences for more or less decentralisation.
Co-creating research at The AI, media, and democracy lab: Reflections on the role of academia in collaborations with media partners
Authors: Cools Hannes , Helberger Natali , de Vreese Claes
Published: February 2025

This commentary explores academia’s role in co-creating research with media partners, focusing on the distinct roles and challenges that each stakeholder brings to such partnerships. Starting from the perspective of the AI, Media, and Democracy Lab, and building on the Ethical, Legal, and Societal Aspects (ELSA) approach, we share key learnings from 3 years of collaborations with (media) partners. We conclude that navigating dual roles, expectations, output alignment, and a process of knowledge sharing are important requirements for academics and (media) partners to adequately co-create research and insights. We also argue that these key lessons do not always square with how academic research is organized and funded. We underscore that changes in funding structures and the way academic research is assessed can further facilitate the co-creation of research between academic research and projects in the media sector.
Endovascular Aortic Aneurysm Repair for Abdominal Aortic Aneurysm With Type V Horseshoe Kidney
Authors: Wu Mingwei , Xiong Jiang
Published: February 2025

Purpose:

Abdominal aortic aneurysm (AAA) with concomitant Horseshoe kidney (HSK) is rare. When open surgery is not feasible, preserving the renal isthmus artery (RIA) during endovascular treatment presents a challenge.

Case report:

A 70-year-old male presented with a 57.8 mm × 54.3 mm AAA and type V HSK perfused by a 4.4 mm RIA from the inferior mesenteric artery and a 4.6 mm RIA from the aortic bifurcation. This case report describes an endovascular aortic aneurysm repair (EVAR) performed on an AAA coexisting with a type V HSK. One-year follow-up: the AAA had regressed, and the HSK remained perfused without any endoleak or increase in serum creatinine levels.

Conclusion:

The utilization of EVAR offers a feasible option for AAA combined with type V HSK, particularly in cases of high surgical risk.

Clinical Impact

In Abdominal aortic aneurysm (AAA) with type V horseshoe kidney (HSK), preserving renal isthmus arteries (RIAs) is critical when they provide a substantial portion of the HSK blood supply.When open surgery is not feasible, preserving the RIA during endovascular treatment presents a challenge.The use of EVAR, incorporating a periscope stent and embolization, provides a viable treatment option for patients with AAA and type V HSK, especially in high surgical risk cases.
Risk of postoperative bleeding and thromboembolic events in anticoagulated patients undergoing transurethral resection of bladder tumors
Authors: Scherer Thomas Paul , Dam Cici , Bieri Uwe , Eberli Daniel , Strebel Raeto
Published: February 2025

Background:

Transurethral resection of the bladder (TURB) harbors a high-risk for postoperative bleeding, especially in patients requiring anticoagulation. Recently, direct oral anticoagulants (DOACs) have become a popular alternative to vitamin K antagonists (VKAs), though their impact on TURB complications remains unclear.

Objectives:

To assess the postoperative complications of TURB from patients taking DOACs and VKAs.

Design:

Retrospective cohort study.

Materials and methods:

We retrospectively identified anticoagulated patients undergoing a TURB at our institution between 2012 and 2022 and divided them into two groups: whether they received VKA or DOAC. Follow-up of each patient was performed for 3 months. Occurrence and time to event of postoperative bleeding and thromboembolic events were recorded. A multivariable regression analysis was performed to assess risk differences.

Results:

A total of 167 patients (11.7%) fulfilled the inclusion criteria, of which 102 patients (61.1%) received a DOAC and 65 patients (38.9%) a VKA. Postoperative bleeding led to re-catheterization in 13 (12.8%) DOAC and 6 (9.2%) VKA patients ( p = 0.49) and re-intervention in 7 (6.9%) DOAC and 4 (6.2%) VKA patients ( p = 0.86). Blood transfusions were administered to 3 DOAC patients (2.9%), none in the VKA group. No thromboembolic events were reported.

Conclusion:

TURB carries low morbidity in anticoagulated patients. Thromboembolic events and the need for blood transfusion are infrequent. No substantial difference between the postoperative bleeding risk of patients receiving DOAC or VKA was found. All bleeding complications occurred within 2 weeks, marking it a potentially safe point in time to restart the OAC thereafter.
Performance of Three Continuous Glucose Monitoring Systems in Adults With Type 1 Diabetes
Authors: Eichenlaub Manuel , Waldenmaier Delia , Wehrstedt Stephanie , Pleus Stefan , Link Manuela , Jendrike Nina , Öter Sükrü , Haug Cornelia , Schinz Maren , Braunack-Mayer Vincent , Schneider Regula , Brandt Derek , Freckmann Guido
Published: February 2025

Background:

The performance of continuous glucose monitoring (CGM) systems is difficult to compare due to different study designs and a lack of head-to-head studies. This study evaluated the performance of FreeStyle Libre 3 (FL3), Dexcom G7 (DG7), and Medtronic Simplera (MSP) against different comparator methods and during clinically relevant glycemic scenarios.

Method:

Twenty-four adult participants with type 1 diabetes mellitus wore one sensor of each CGM system in parallel for up to 15 days. Sensors of DG7 and MSP were exchanged on days 5 and 8, respectively. Three 7-hour sessions with 15-minute comparator blood glucose–level measurements using YSI 2300 (YSI, venous), Cobas Integra (INT, venous), and Contour Next (CNX, capillary) were conducted on days 2, 5, and 15. Simultaneously, glucose-level excursions with transient hyperglycemia and hypoglycemia were induced according to a recently published testing procedure. The accuracy was evaluated using various metrics, including mean absolute relative differences (MARDs).

Results:

Compared with YSI data, the MARDs of FL3, DG7, and MSP were 11.6%, 12.0%, and 11.6%, respectively. Relative to the INT data, the corresponding MARDs were 9.5%, 9.9%, and 13.9%, respectively, and compared with CNX data, MARDs were 9.7%, 10.1%, and 16.6%, respectively. Both FL3 and DG7 showed better accuracy in the normoglycemic and hyperglycemic range, while MSP performed better in the hypoglycemic range.

Conclusions:

Performance results of all CGM systems varied depending on the comparator method. However, across comparators FL3 and DG7 tended to be more accurate compared with MSP. All CGM systems showed a lower accuracy compared with previous studies, emphasizing the need for comprehensive study design guidelines.
Effect of selective suture removal on graft astigmatism after corneal transplantation in keratoconus
Authors: Feizi Sepehr , Javadi Mohammad Ali , Karjou Zahra , Nouri Nasim , Oraeeyazdani Maryam , Khorrami Zahra , Esfandiari Hamed
Published: February 2025

Background:

Selective suture removal has been demonstrated to be effective in reducing post-keratoplasty astigmatism, while the remaining sutures are left in place. Existing studies typically focus on outcomes immediately after selective suture removal, without delving into the final suture-out keratometric astigmatism.

Objectives:

To examine the impact of selective suture removal on corneal graft astigmatism following keratoplasty in keratoconus and identify potential factors associated with the changes in graft astigmatism after suture removal.

Design:

Retrospective, comparative interventional case series.

Methods:

The study included 118 consecutive eyes of 118 cases that underwent corneal transplantation for keratoconus and had a keratometric astigmatism of ⩾4 D. One or two interrupted sutures corresponding to the steep meridian were removed per session. Patients were re-evaluated at 1 to 2-month intervals, repeating the procedure until achieving a keratometric astigmatism of <4.0 D or no interrupted sutures remained in the steep meridian.

Results:

The mean recipient age was 28.4 ± 8.4 years. A total of 234 selective suture removals were performed, with a mean of 2.0 ± 1.1 removals per eye. Pre-suture removal keratometric astigmatism significantly decreased from 6.3 ± 2.0 D to 3.91 ± 2.23 D after the completion of selective suture removal ( p < 0.001). This value was significantly increased to 5.45 ± 2.93 D after all suture removal ( p < 0.001). Higher pre-suture removal astigmatism and deep anterior lamellar keratoplasty were associated with a more favorable response to selective suture removal.

Conclusion:

Selective suture removal effectively modifies graft curvature to reduce post-keratoplasty astigmatism in keratoconus patients. However, its efficacy markedly diminishes after all sutures are removed. This procedure is particularly effective in patients with higher pre-suture removal astigmatism and those undergoing deep anterior lamellar keratoplasty.
Rescue of common and rare exon 2 skipping variants of the GAA gene using modified U1 snRNA
Authors: Peruzzo Paolo , Bergamin Natascha , Bon Martina , Cappelli Sara , Longo Alessandra , Goina Elisa , Stuani Cristiana , Buratti Emanuele , Dardis Andrea
Published: February 2025

Background

Pompe disease (PD) is an autosomal recessive lysosomal storage disorder caused by the deficient activity of acid alpha glucosidase (GAA) enzyme due to mutations in the GAA gene. As a result, undigested glycogen accumulates within lysosomes causing their dysfunction. From a clinical point of view, the disease can be classified in infantile-onset (IO) and late-onset (LO) forms. The common GAA c.-32-13T>G variant, found in 40–70% of LO-PD alleles, is a leaky splicing mutation interfering with the correct GAA exon 2 recognition by the spliceosome leading to the production of non-functional GAA transcripts. In this study, we used modified, GAA-tailored U1 snRNAs to correct the aberrant splicing determined by the c.-32-13T>G and other GAA exon 2-skipping mutations.

Methods

A set of constructs expressing 5 different engineered U1 snRNAs was generated. A functional splicing assay using a GAA hybrid minigene carrying different variants known to affect GAA exon 2 splicing was used to test the effect of engineered U1 snRNAs on exon 2 inclusion. The effect on endogenously expressed GAA transcript and GAA enzymatic activity was assessed by transfecting patient-derived fibroblasts bearing the common c.-32-13T>G with the best performing modified U1 snRNA.

Results

Modified U1-3, U1+1 and U1+6 snRNAs were all able to increase, in a dose-dependent manner, the inclusion of exon 2 within the transcript derived from the GAA minigene harbouring the c.-32-13T>G variant. The U1+1 was the most effective one (2,5 fold increase). Moreover, U1+1 snRNA partially rescued the correct splicing of GAA minigenes harbouring mutations that affect the 3’ss (c.-32-3C>G, c.-32-2A>G) and the 5’ss (c.546G>A, c.546G>C, c.546G>T). Notably, the treatment of patient-derived fibroblasts carrying the c.-32-13T>G mutation with the U1+1 snRNA increased the amount of normal GAA mRNA by 1,8 fold and the GAA enzymatic activity by 70%.

Conclusions

we provide the proof-of-concept for the use of modified GAA-tailored U1 snRNAs, designed to potentiate the recognition of the GAA exon 2 5’ss, as therapeutic tools to correct the aberrant transcripts carrying variants that affect exon 2 splicing, including the common c.-32-13T>G variant.
TAB2 deficiency induces dilated cardiomyopathy by promoting mitochondrial calcium overload in human iPSC-derived cardiomyocytes
Authors: Sun Wenrui , Zhang Jianchao , Li Shuang , Fu Wanrong , Liu Yangyang , Liu Mengduan , Dong Jianzeng , Zhao Xiaoyan , Li Xiaowei
Published: February 2025

Background

TGF-β-activated kinase 1 binding protein 2 (TAB2) is an intermediary protein that links Tumor necrosis factor receptor 1 (TNFR1) and other receptor signals to the TGF-β-activated kinase 1 (TAK1) signaling complex. TAB2 frameshift mutations have been linked to dilated cardiomyopathy (DCM), while the exact mechanism needs further investigation.

Methods

In this study, we generated a TAB2 compound heterozygous knockout cell line in induced pluripotent stem cells (iPSCs) derived from a healthy individual using CRISPR/Cas9 technology. IPSCs are not species-dependent, are readily accessible, and raise fewer ethical concerns.

Results

TAB2 disruption had no impact on the cardiac differentiation of iPSCs and led to confirmed TAB2 deficiency in human iPSC-derived cardiomyocytes (hiPSC-CMs). TAB2-deficient hiPSC-CMs were found to develop phenotypic features of DCM, such as distorted sarcomeric ultrastructure, decreased contractility and energy production, and mitochondrial damage at day 30 post differentiation. Paradoxically, TAB2 knockout cell lines showed abnormal calcium handling after 40 days, later than reduced contractility, suggesting that the main cause of impaired contractility was abnormal energy production due to mitochondrial damage. As early as day 25, TAB2 knockout cardiomyocytes showed significant mitochondrial calcium overload, which can lead to mitochondrial damage. Furthermore, TAB2 knockout activated receptor-interacting protein kinase 1 (RIPK1), leading to an increase in mitochondrial calcium uniporter (MCU) expression, thereby augmenting the uptake of mitochondrial calcium ions. Finally, the application of the RIPK1 inhibitor Nec-1s prevents the progression of these phenotypes.

Conclusions

In summary, TAB2 abatement cardiomyocytes mimic dilated cardiomyopathy in vitro. This finding emphasizes the importance of using a human model to study the underlying mechanisms of this specific disease. More importantly, the discovery of a unique pathogenic pathway introduces a new notion for the future management of dilated cardiomyopathy.
Collagen turnover biomarkers to predict outcome of patients with biliary cancer
Authors: Kaps Leonard , Genc Muhammed A. , Moehler Markus , Grabbe Stephan , Schattenberg Jörn M. , Schuppan Detlef , Pedersen Rasmus Sund , Karsdal Morten A. , Mildenberger Philipp , Maderer Annett , Willumsen Nicholas
Published: February 2025

Background

The collagen-rich tumor stroma plays a crucial role in biliary tract cancer (BTC). Collagen biomarkers of type I collagen (reC1M), type III collagen (PRO-C3), type IV collagen (C4G), type VIII collagen (PRO-C8), type XI collagen (PRO-C11), type XVII collagen (PRO-C17) and type VIII collagen (TUM) may be used as potential non-invasive biomarkers.

Methods

We measured the seven biomarkers of collagen turnover in sera of 72 patients with BTC at baseline and after first and second chemotherapy cycle (CTX). Markers were also assessed in sera of 50 healthy controls and compared to levels of patients at baseline. The diagnostic and prognostic value of the markers was evaluated for overall survival (OS) and progression-free survival (PFS).

Results

Patients had a median age of 65 years (IQR 57–70), while healthy controls were younger, with a median age of 46 years (IQR 38–54). The majority of patients (62%) were diagnosed with intrahepatic bile duct adenocarcinoma. Except C4G, all collagen turnover markers were significantly (p < 0.001) increased in serum from patients with BTC compared to healthy controls. PRO-C3 was the best marker to discriminate between patients with BTC and controls, reaching an area under a receiver operating characteristic (AUROC) of 0.98 (95% CI 0.95; 0.99) with a sensitivity (92%) and specificity (94%) balanced cutoff of 77.3 ng/ml. Patients with high levels (cohort separated by median split) of PRO-C8 (HR 2.85, 95% CI 1.42; 5.73) followed by C3M (HR 2.33, 95% CI 1.2; 4.5), PRO-C3 (HR 3.09, 95% CI 1.5; 6.36) and CA 19–9 (HR 2.52, 95% CI 1.37; 4.64) as reference biomarker had a shorter OS. Notably, only the novel marker PRO-C8 was also predictive of PFS (HR 3.26, 95% CI 1.53; 6.95). Associations with survival outcomes remained significant after adjusting for relevant risk factors (CA 19–9 and CEA at baseline, age, presence of metastases, weight, height and gender).

Conclusion

The collagen turnover markers PRO-C8, C3M, PRO-C3 and the established biomarker CA 19–9 were prognostic for OS in patients with BTC while only PRO-C8 was also predictive for PFS. PRO-C3 showed the best diagnostic performance to discriminate between patients with BTC and controls.

Trial registration

Trial registration number and date of registration

NCT00661830 (NCT number)

15 April 2008

Trial registry

The complete registry can found under:

https://clinicaltrials.gov/study/NCT00661830?tab=table#administrative-information (last accessed 01/2025)

Principal investigator and study sponsor

Markus Moehler, MD

Johannes Gutenberg University Mainz
Assessment of in vitro skin permeation and accumulation of phenolic acids from honey and honey-based pharmaceutical formulations
Authors: Nowak Anna , Muzykiewicz-Szymańska Anna , Perużyńska Magdalena , Kucharska Edyta , Kucharski Łukasz , Jakubczyk Karolina , Niedźwiedzka-Rystwej Paulina , Stefanowicz-Hajduk Justyna , Droździk Marek , Majtan Juraj
Published: February 2025

Background

Honey has been successfully used in wound care and cosmetics because of its effective biological properties, including antibacterial, antioxidant, and anti-inflammatory activities. Polyphenols, particularly phenolic acids, are key honey components responsible for these beneficial effects. In recent years, there has been a growing demand for natural, ecologically friendly, and biodegradable products in the modern cosmetics and wound care market. This study aimed to identify and quantify phenolic acids in four Polish honey samples of different botanical origins (heather, buckwheat, linden and rapeseed) and to assess for the first time the permeation of the identified phenolic acids through the skin and their accumulation after the application of pure honey samples, as well as honey-based hydrogel and emulsion formulations.

Methods

The honey samples’ antioxidant activity and total phenolic content were determined using the DPPH and ABTS assays and the Folin–Ciocalteu method, respectively. Phenolic acids and volatile compounds were identified and quantified in honey samples using the HPLC-UV and GC-MS method, respectively. The biocompatibility of the honey samples was evaluated using a murine fibroblast cell line (L929). A Franz-type vertical diffusion cell with porcine skin was used to assess phenolic acid’s permeation and skin accumulation from different honey-based pharmaceutical formulations. The biodegradability of the prepared formulations was also characterised.

Results

Gallic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid, coumaric acid, and 3-hydroxybenzoic acid were identified and quantified in the honey samples. Heather honey exhibited significantly higher antioxidant activity and total polyphenol content than the other honey samples. Heather, linden and buckwheat honey samples significantly decreased cell viability at concentrations of 5% and 2.5%, while rapeseed honey sample markedly reduced fibroblast viability only at 5%. Among the tested formulations - pure honey, hydrogel, and emulsion - higher skin permeation and accumulation rates of phenolic acids were observed with the prepared honey-based hydrogels than with the pure honeys and emulsions. Additionally, the prepared formulations were classified as partially biodegradable.

Conclusions

The obtained results confirmed the effectiveness of two pharmaceutical formulations in the form of a hydrogel or emulsion containing honey after applied topically. The inclusion of honey in the vehicle, in particular hydrogel increased the penetration of phenolic acids through the skin.
Immune microenvironment spatial landscapes of tertiary lymphoid structures in gastric cancer
Authors: Xie Yi , Peng Haoxin , Hu Yajie , Jia Keren , Yuan Jiajia , Liu Dan , Li Yanyan , Feng Xujiao , Li Jian , Zhang Xiaotian , Sun Yu , Shen Lin , Chen Yang
Published: February 2025

Background

Tertiary lymphoid structures (TLS) correlate with tumour prognosis and immunotherapy responses in gastric cancer (GC) studies. However, understanding the complex and diverse immune microenvironment within TLS requires comprehensive analysis.

Methods

We examined the prognostic impact of TLS within the tumour core (TC) of 59 GC patients undergoing immunotherapy. Multispectral fluorescence imaging was employed to evaluate variations in immune cell infiltration across different TLS sites among 110 GC patients, by quantifying immune cell density and spatial characteristics. We also generated a single-cell transcriptomic atlas of TLS-positive (n = 4) and TLS-negative (n = 8) microenvironments and performed spatial transcriptomics (ST) analysis on two samples.

Results

TLS presence in the TC significantly correlated with improved immune-related overall survival (P = 0.049). CD8+LAG-3−PD-1+TIM-3−, CD4+PD-L1+, and CD4+FoxP3− T cell densities were significantly higher in the TLS within TC compared to tumour and stromal regions. Immune cells within TLS exhibited closer intercellular proximity than those outside TLS. Five key density and spatial characteristics of immune cells within TLS in the TC were selected to develop the Density and Spatial Score risk model. Single-cell RNA sequencing revealed strong intercellular interactions in the presence of TLS within the microenvironment. However, TLS-absent environment facilitated tumour cell interactions with immune cells through MIF- and galectin-dependent pathways, recruiting immunosuppressive cells. ST analysis confirmed that T and B cells co-localise within TLS, enhancing immune response activation compared to cancer nests and exerting a strong anti-tumour effect.

Conclusions

TLS presence facilitates frequent cell-to-cell communication, forming an active immune microenvironment, highlighting the prognostic value of TLS.
Cervical pedicle screw fixation with the Tianji orthopedic surgical robot
Authors: Shen Hao , Zhou Jinlong , Yu Lipeng
Published: February 2025

Objective

To compare the accuracy and safety of implanting cervical pedicle screws (CPS) between orthopedic surgical robot-assisted technique and traditional fluoroscopy-assisted free-hand technique.

Methods

Retrospective analysis of 95 patients treated with posterior cervical spinal surgery using either Tianji orthopedic surgical robot-assisted or traditional fluoroscopy-assisted free-hand pedicle screw implantation technology from March 2021 to March 2024, including 44 cases in the orthopedic surgical robot group and 51 cases in the traditional fluoroscopy group.

Results

Compared with the traditional fluoroscopy group, the orthopedic surgical robot group had better accuracy in screw implantation that is, a higher acceptable rate of screws (p = 0.0083). In addition, compared with the traditional fluoroscopy group, postoperative hospital stay was shorter in the orthopedic surgical robot group (p = 0.0447), but operation duration was longer (p = 0.0038). There was no significant difference in intraoperative blood loss between groups (p = 0.0872). There were 2 cases of cerebrospinal fluid leakage and 1 case of decreased left handgrip strength in the traditional fluoroscopy group, while only 1 case of cerebrospinal fluid leakage occurred in the orthopedic surgical robot group.

Conclusions

In this retrospective study, the accuracy of spine surgery with CPS implantation assisted by orthopedic surgical robot is often superior to that of spine surgery using traditional fluoroscopy-guided CPS implantation technique, while maintaining comparable safety.
Metabolites and lipid species mediate the associations of adiposity in childhood and early adulthood with mammographic breast density in premenopausal women
Authors: Getz Kayla R. , Jeon Myung Sik , Liu Lili , Liu Lei , Zhang Haixiang , Luo Chongliang , Luo Jingqin , Toriola Adetunji T.
Published: February 2025

Background

Mammographic breast density (MBD), a strong predictor of breast cancer, is highly influenced by body mass index (BMI) in childhood and early adulthood, but the mechanisms underlying these associations are not fully understood. Our goal is to identify biomarkers that mediate the associations of BMI at ages 10 and 18 with MBD in premenopausal women.

Methods

This study consists of 705 premenopausal women who had their screening mammogram at Washington University in St. Louis, MO, and provided a fasting blood sample. Our comprehensive metabolomic and lipidomic profiling yielded complete data for 828 metabolites and 857 lipid species after imputation. We used Volpara to determine volumetric measures of MBD. We performed high dimensional mediation analysis using the HIMA R package, adjusted for confounders, to determine whether lipid species and metabolites mediate the associations of BMI at 10 and 18 with MBD. We applied a false discovery rate (FDR) p-value < 0.1.

Results

Four metabolites (glutamate, β-cryptoxanthin, cortolone glucuronide (1), phytanate) significantly mediated the association of BMI at 10 with volumetric percent density (VPD), and two (glutamate, β-cryptoxanthin) mediated the association of BMI at 18 with VPD. Glutamate was the strongest mediator across time points. Glutamate mediated 6.7% (FDR p-value = 0.06) and 9.3% (FDR p-value = 0.008) of the association between BMI at age 10 and 18, respectively. Four lipid species (CER(18:0), LCER(14:0), LPC(18:1), PC(18:1/18:1)), mediated the association of BMI at 10 with VPD, while five lipid species (CER(18:0), LCER(14:0), PC(18:1/18:1), TAG56:5-FA22:5, TAG52:2-FA16:0) mediated the association of BMI at 18 with VPD. The strongest mediator was PC(18:1/18:1), which mediated 9.7%, (FDR-p = 0.009) and 7.7%, (FDR-p = 0.04) of the association of BMI at age 10 and 18 with VPD, respectively.

Conclusions

Metabolites in amino acid, lipid, cofactor/vitamin, and xenobiotic super-pathways as well as lipid species across the phospholipid, neutral complex lipid and sphingolipid super-pathways mediated the associations of BMI in early-life and MBD in premenopausal women. This study offers insight into the biological mechanisms underlying the link between early-life adiposity and MBD, which can support future research into breast cancer prevention.
Merck Open Global Health Library in vitro screening against Schistosoma mansoni identified two new substances with antischistosomal activities for further development
Authors: Ueberall Monique Evelyn , Berchthold Martina , Häberli Cécile , Lindemann Sven , Spangenberg Thomas , Keiser Jennifer , Grevelding Christoph G.
Published: February 2025

Background

Schistosomiasis, which is caused by the parasite Schistosoma mansoni as well as other species of the trematode genus Schistosoma, leads to chronic inflammation and finally to liver fibrosis. If untreated, the disease can cause life-threatening complications. The current treatment of schistosomiasis relies on a single drug, praziquantel (PZQ). However, there is increasing concern about emerging resistance to PZQ due to its frequent use.

Methods

To identify potential alternative drugs for repurposing, the Open Global Health Library (OGHL) was screened in vitro, using two different screening workflows at two institutions, against adult S. mansoni couples and newly transformed schistosomula. This was followed by confirmation of the effects of the lead structures against adult worms.

Results

In vitro screening at one of the institutions identified two fast-acting substances affecting worm physiology (OGHL00022, OGHL00121). The effects of the two lead structures were investigated in more detail by confocal laser scanning microscopy and 5-ethynyl 2´-deoxyuridine (EdU) assays to assess morphological effects and stem cell effects. Both substances showed negative effects on stem cell proliferation in S. mansoni but no further morphological changes. The EC50values of both compounds were determined, with values for compound OGHL00022 of 5.955 µM for pairing stability, 10.88 µM for attachment, and 18.77 µM for motility, while the values for compound OGHL00121 were 7.088 µM for pairing stability, 8.065 µM for attachment, and 6.297 µM for motility 24 h after treatment. Furthermore, S. mansoni couples were treated in vitro with these two lead structures simultaneously to check for additive effects, which were found with respect to reduced motility. The second in vitro screening, primarily against newly transformed schistosomula and secondarily against adult worms, identified four lead structures in total (OGHL00006, OGHL00022, OGHL00169, OGHL00217). In addition, one of the tested analogues of the hits OGHL00006, OGHL00169, and OGHL00217 showed effects on both stages.

Conclusions

In two independent in vitro screening approaches against two stages of S. mansoni one common interesting structure with rapid effects was identified, OGHL00022, which provides opportunities for further development.

Graphical Abstract
Sex differences in the neuroinflammatory signaling pathway: effect of miRNAs on fatty acid synthesis in microglia
Authors: Zheng Haolin , Mizokami Akiko , Romera-Giner Sergio , Llera-Oyola Jaime , Yamawaki Yosuke , Sano Tomomi , Jimi Eijiro , García-García Francisco , Kanematsu Takashi
Published: February 2025

Background

Significant sex differences exist in the prevalence and incidence of Alzheimer’s disease (AD). Notably, testosterone has been reported to regulate cognitive functions in the brain, with low serum testosterone levels correlating with increased AD risk. However, the specific mechanisms underlying this relationship remain unclear. Recent studies have demonstrated that microglia, the primary innate immune cells in the brain, play a crucial role in AD development. Therefore, this study aimed to explore sex differences in microglial function, specifically focusing on the role of testosterone in miRNA-mediated regulation of microglial gene expression.

Methods

Microglia were isolated from pooled hippocampal tissue of five 8-month-old male and female mice. Total RNA was extracted and subjected to miRNA microarray analysis. The mouse microglial cell line MG6 was used for in vitro experiments. Following testosterone treatment, miRNA, gene, and protein expression levels were investigated. An inflammatory response was induced using lipopolysaccharide (LPS) stimulation, and subsequent p65 phosphorylation was assessed.

Results

Sex-dependent differences were observed in miRNA-mediated biological processes, with males exhibiting greater changes. Male-enriched miRNAs were associated with fatty acid synthesis and metabolism pathways. In MG6 cells, testosterone treatment upregulated the expression of several miRNAs enriched in male microglia, particularly those targeting genes related to fatty acid synthesis. Additionally, testosterone significantly reduced the gene expression of fatty acid synthase (FASN). This testosterone-induced inhibition of FASN expression attenuated NF-κB/p65 phosphorylation. Consequently, the suppression of FASN expression led to reduced expression and secretion of tumor necrosis factor-alpha following LPS stimulation in MG6 cells.

Conclusions

These findings suggest that testosterone modulates inflammation in male microglia by regulating fatty acid synthesis, potentially contributing to the observed sex differences in AD pathogenesis.
Effect of exercise training on cardiac autonomic function in type 2 diabetes mellitus: a systematic review and meta-analysis
Authors: Raje Sohini , Maiya G Arun , R Padmakumar , Prabhu Mukund A. , Nayak Krishnananda , KN Shivashankara , Shastry BA , Nataraj Megha
Published: February 2025

Background

Cardiac autonomic neuropathy (CAN) is an underdiagnosed complication of type 2 diabetes mellitus (T2DM) and is associated with cardiovascular morbidity and mortality. Cardiac autonomic reflex tests (CARTs) are the gold standard; they are non-invasive and clinically feasible for screening CAN. The objective of the present meta-analysis was to examine exercise’s effect on cardiac autonomic function using CARTs in T2DM.

Methods

The Preferred Reporting Items for Systematic Review and Meta-Analysis Checklist (PRISMA) was used. Electronic databases were systematically used to retrieve relevant studies after title and abstract screening. Studies utilizing exercise training with cardiac autonomic function (CARTs) outcomes in individuals with type 2 diabetes mellitus were included. The meta-analysis was conducted using RevMan 5.4.1, using the random effects model, and appropriate tests for heterogeneity. The Cohrane ROB-2 tool was used for randomized controlled trials (RCTs) and the ROBINS-I tool for non-RCT for risk of bias assessment were used.

Results

Three studies were included (two for meta-analysis), considering the outcome of the E:I ratio, 30:15 ratio, and Valsalva ratio. The studies did not show any influence on the E:I and 30:15 ratio in the pooled analysis with a low risk of ineffectiveness for the exercise intervention. Exercise training significantly affected the Valsalva ratio. A different type of exercise intervention was utilized in all three studies. There was a low to moderate certainty for the evidence.

Conclusion

The results indicate that further robust and high-quality randomized controlled trials utilizing cardiac autonomic reflex tests (which have clinical and physiological relevance) in type 2 diabetes mellitus are required for drawing conclusions.

Systematic review registration

PROSPERO CRD42023445561.
Global biogeography and projection of antimicrobial toxin genes
Authors: Liu Ya , Geng Yu , Jiang Yiru , Sun Jingyu , Li Peng , Li Yue-zhong , Zhang Zheng
Published: February 2025

Background

Antimicrobial toxin genes (ATGs) encode potent antimicrobial weapons in nature that rival antibiotics, significantly impacting microbial survival and offering potential benefits for human health. However, the drivers of their global diversity and biogeography remain unknown.

Results

Here, we identified 4400 ATG clusters from 149 families by correlating 10,000 samples worldwide with over 200,000 microbial genome data. We demonstrated that global microbial communities universally encode complex and diverse ATGs, with widespread differences across various habitats. Most ATG clusters were rare within habitats but were shared among habitats. Compared with those in animal-associated habitats, ATG clusters in human-associated habitats exhibit greater diversity and a greater proportion of sharing with natural habitats. We generated a global atlas of ATG distribution, identifying anthropogenic factors as crucial in explaining ATG diversity hotspots.

Conclusions

Our study provides baseline information on the global distribution of antimicrobial toxins by combining community samples, genome sequences, and environmental constraints. Our results highlight the natural environment as a reservoir of antimicrobial toxins, advance the understanding of the global distribution of these antimicrobial weapons, and aid their application in clinical, agricultural, and industrial fields.
Post-COVID-19 resurgence of scabies’ cases in the Lazio Region, Italy: a new emerging public health threat?
Authors: Spaziante Martina , Agresta Alessandro , D’Amato Maurizio , De Carli Gabriella , Tonziello Gilda , Vantaggio Valentina , Malatesta Giorgio Nicolò , Girardi Enrico , Barca Alessandra , Scognamiglio Paola , Vairo Francesco
Published: February 2025

Scabies represents a global health issue and in 2017 was added to the World Health Organization’s list of neglected tropical diseases. In European and Middle Eastern countries, cases are sporadic while recent surveillance data have pointed out an increasing incidence among vulnerable populations. Regional cases for Lazio, Italy, reported from 2017 to 2023 to the national infectious disease surveillance system were analyzed. In Lazio, just after the coronavirus disease 2019 (COVID-19) pandemic onset, a significant and immediate reduction in the incidence of scabies was recorded (− 79.6%) followed by a progressive and relevant increase (143.4% from 2020 to 2021, 142.3% from 2021 to 2022 and 170.3% from 2022 to 2023). Consistently, the number of scabies outbreaks, after a decrease following the first COVID-19 wave, has progressively increased over time, mainly due to the occurrence of outbreaks in long term facilities (750% from 2020 to 2023). The increased incidence may also be driven by the “pseudo-resistance” phenomenon (under dosed/early-discontinued treatment, suboptimal adherence, reduced drug bioavailability), but also by reduced in-vitro susceptibility to the mainly used scabicides. The rapidly evolving epidemiology of scabies in our country, as documented also in other regions, calls for a comprehensive approach to effectively address the problem.
Retention in engineering pathways: an ecological belonging intervention supports help-seeking and continued enrollment
Authors: Bahnson Matthew , Godwin Allison , Schunn Christian , McChesney Eric , DeAngelo Linda
Published: February 2025

Background

The demand for engineers in the workforce continues to rise, which requires increased retention and degree completion at the undergraduate level. Engineering educators need to better understand opportunities to retain students in engineering majors. A strong sense of belonging in engineering represents one important contributor to persistence. However, research has not investigated how academic help-seeking behaviors relate to belonging and downstream outcomes, such as persistence in engineering. Interventions to support and develop belonging show promise in increasing student retention, with particularly positive influences on women, Black, Latino/a/x, and indigenous students. As part of a larger research project, a quasi-experimental intervention to develop a classroom ecology of belonging was conducted at a large Midwestern university in a required first-year, second-semester engineering programming course. The 45-min intervention presented students with stories from past students and peers to normalize academic challenges within the ecology of the classroom as typical and surmountable with perseverance, time, and effort.

Results

With treatment (n = 737) and control (n = 689) participant responses, we investigated how the intervention condition affected students' comfort with seeking academic help and feeling safe being wrong in class as influences on belonging. Using path analysis, a form of structural equation modeling, we measured the influence of these attitudinal variables on belonging and the influence of belonging beyond a student’s grade point average on enrollment as an engineering major the following fall. The path analysis supports the importance of academic help-seeking and feeling safe to be wrong for belonging, as well as the importance of belonging on continued enrollment. A group path analysis compared the treatment and control groups and demonstrated the positive impact of the intervention on enrollment for the treatment participants.

Conclusions

The analyses demonstrate the importance of academic help-seeking in students’ sense of belonging in the classroom with implications for identifying effective tools to improve students’ sense of belonging through supporting help-seeking behaviors.
Intracranial desmoid tumor simulating a trigeminal schwannoma: case report and literature review
Authors: Fernandes Beatrice Silva , Vasconcelos Jessica Fernandes , Goncalves Paulo Eduardo , de Souza Junior Joilson Francisco , Gurgel Ricardo Queiroz , Oliveira Arthur Maynart Pereira
Published: February 2025

Background

Desmoid tumor (DT) is a non-encapsulated and locally aggressive benign neoplasm. Although it does not have malignant behavior, it has a high capacity for local growth. Intracranial DTs are extremely rare and constitute a major diagnostic and therapeutic challenge. In these cases, neurosurgical intervention is the best option and should be performed early; however, it is still little discussed in the literature.

Case presentation

We report the case of a 50-year-old male patient, complaining of pain in the region of the right ear and discomfort in the region of the maxilla on the same side for 5 months. Contrast-enhanced magnetic resonance image (MRI) of the skull base and face showed a homogeneous contrast uptake lesion in the region of Meckel’s cave extending inferiorly to the infratemporal fossa with an intracranial and extracranial portion. The patient underwent partial resection of the lesion. The anatomopathological examination showed an infiltrative fibroproliferative lesion (“desmoid-like”), and immunohistochemistry showed myofibroblastic differentiation leading to the possibility of DT. Despite two attempts, the difficult related to skull base location and local invasiveness and the sarcomatous transformation our patient evolved with death 23 months after the diagnosis.

Conclusions

Intracranial DT is a rare and difficult-to-control condition, because despite being considered benign, its infiltrative nature becomes a challenge in neurosurgical management. Neurosurgery has a positive impact on the quality of life of these patients, considering the improvement of symptoms and the possibility of making a more appropriate diagnosis.
The role of simultaneous stereotactic biopsy and radiofrequency ablation in the management of brain neoplasms in countries with limited financial resources
Authors: Mahmoud Mohamed Ashraf , El Gayar Abdelrahman , El Molla Shafik T , Radwan Hesham , El Serry Tarek H , Al Abyad Ashraf
Published: February 2025

Background

Heat can help control the progression of intra-axial cerebral neoplasms in selected cases. RF (Radiofrequency) is available and cost effective in resource-limited settings. RF stereotactic heat was delivered simultaneously with the biopsy in brain tumors.

Objective

We evaluated the safety and feasibility of stereotactic RF ablation of intra-axial brain neoplasms during stereotactic brain biopsy procedure.

Methods

Twenty-two adult patients were treated with interstitial hyperthermia by RF plus stereotactic brain tumor biopsy in Ain shams University Hospitals from 2022 to 2024. Follow-up for tumor progression was done over a period of 12 months.

Results

A total of 22 participants have been enrolled; follow-up period was 12 months. There were 12 (54.5%) females and 10 (45.5%) males. The mean and median ages were 53.6 years (range 25–72) and 54 years, respectively. 72.6% had at least a single baseline comorbidity. From the ablated tumors, 17 were primary, 4 were metastatic, and 1 was in-field necrosis. Median tumor volume was 6 cm3 and mean was 10.2 cm3 (range, 0.5–40 cm3). The one-year estimated survival rate was 86.6%, and this was impacted by disease etiology.

Conclusions

Results from this study demonstrate that RF ablation is a safe technique that it can be used simultaneously with stereotactic biopsy in selected cases of intra-axial brain neoplasms. A potential trend of longer progression-free interval of tumor is presumed in the cases. In resource-limited settings, RF ablation can be a safe and available alternative to LITT (Laser Interstitial Thermocoagulative Therapy) that can deliver heat to intracranial tumors.
The effect of mild-stage Alzheimer’s disease on the acoustic parameters of voice
Authors: Arslan-Sarımehmetoğlu Emel , Barmak Elife
Published: February 2025

Objective

Our study aimed to reveal the differences by comparing the objective and subjective voice features of individuals diagnosed with mild-stage Alzheimer’s disease (AD) with those with normal cognitive abilities.

Methods

The study comprised 51 participants, who were divided into two groups: those with AD (study group, n = 28) and those with normal cognitive abilities (control group, n = 23). In the objective voice assessments of the participants, s/z ratio, maximum phonation time (MPT), F0, F1, F2, F3, jitter, shimmer, and NHR values were examined. The Voice Handicap Index-10 (VHI-10) and Voice-Related Quality of Life Scale (V-RQOL) were employed for the subjective assessments.

Results

In both males and females, the jitter and shimmer values in the study group were considerably higher than those in the control group (p < 0.000). The MPT of male participants in the study group was significantly lower than that of male participants in the control group (p < 0.036). Regarding VHI-10 and V-RQOL, the groups showed no statistically significant variation (p > 0.005).

Conclusion

Differences in shimmer, jitter, and MPT values based on gender among individuals with mild-stage AD indicate an impact on voice quality. It is suggested that clinicians should consider voice parameters during the assessment and intervention processes for mild-stage AD.