bluuebunny/crossref_metadata_2025 huggingface dataset:
In situ Forming Nanoemulgel for Diabetic Retinopathy:
Development, characterization, and in vitro efficacy
assessment
Authors: Singh Soumya , Kushwaha Poonam , Gupta Sujeet
Published: February 2025

Diabetic retinopathy, the most common microvascular complication of diabetes
mellitus, is the leading cause of vision impairment worldwide. Flavonoids with
antioxidant properties have been shown to slow its progression. Myricetin, a
flavonoid polyphenolic compound, possesses antioxidant properties, but its
clinical use in ocular delivery is limited by poor aqueous solubility,
stability, and bioavailability. Recently, in situ gels have gained interest as
ocular drug delivery vehicles due to their ease of installation and sustained
drug release. This study aimed to develop a myricetin-loaded thermoresponsive in
situ nanoemulgel to enhance its efficacy in treating diabetic retinopathy.
Nanoemulsions were developed via aqueous phase titration using Sefsol 218 as the
oil phase, Kolliphore RH40 as the surfactant, and PEG 400 as the co-surfactant.
Physicochemical evaluations identified formulation batch ISG17, consisting of
10% oil phase, 30% Smix (1:2), and 60% distilled water, as the
optimal formulation. The developed in situ nanoemulgel showed significant
enhancement in corneal permeation and retention, which was further confirmed by
fluorescence microscopy. Ocular tolerability was demonstrated through corneal
hydration tests and histopathology investigations. The antioxidant potential of
the myricetin-loaded nanoemulgel was assessed using the DPPH assay. Myricetin
was found to be an efficient antioxidant, as indicated by its IC50
values compared to ascorbic acid. The MTT cell viability assay results showed
that the developed formulation effectively inhibits the proliferation of Y79
retinoblastoma cells, demonstrating comparable efficacy to the standard marketed
preparation Avastin (Bevacizumab injection). In conclusion, the nanoemulsion
formulation containing a thermoresponsive polymer for in situ gelling presents a
promising drug delivery system, offering superior therapeutic efficacy and
better patient compliance for the treatment of diabetic retinopathy.
Congenital Lung Malformations: Outcomes after Minimally Invasive and
Open Surgery in Infancy
Authors: Mayer Benjamin Friedrich Berthold , Schöneberg Leon Ole , Schunn Matthias Christian , Kagan Karl Oliver , Schäfer Jürgen , Neunhoeffer Felix , Baden Winfried , Fideler Frank , Kirschner Hans Joachim , Lieber Justus , Fuchs Jörg
Published: February 2025

The management of congenital lung malformations (CLM) remains controversial.
The aim of this study was to analyze the timing, approach, and outcomes of
surgical treatment in children with CLM.

A cohort study was conducted comparing children with CLM who underwent
thoracoscopic resection with open resection via thoracotomy. All children
were treated according to an institutionalized multidisciplinary coordinated
treatment algorithm.

Between 2002 and 2019, 68 children with CLM were treated. Thoracoscopic
resection of CLM (n=44) resulted in a statistically significant longer
operative time (mean 169 vs. 97 minutes, p=0.04) but shorter hospital stay
(mean 7.2 vs. 16.7/12 days, p=0.01) compared to thoracotomy (n=15) or after
conversion to thoracotomy (n=9). There were no major complications in either
group. At a mean follow-up of 32.2 months (range 0.5–163), patients after
thoracoscopic resection had statistically significantly fewer rip fusions
than patients after open resection (n=0 vs. 2/2, p≤0.004) and less chest
wall asymmetry than after conversion (n=0 vs. 2, p=0.004).

Thoracotomy proved to be a fast and safe surgical approach in respiratory
unstable CLM patients. In respiratory stable CLM patients, thoracoscopic
resection was feasible in early infancy with good surgical and
musculoskeletal outcomes.

Thoracoscopic resection of CLM offers advantages over resection by
thoracotomy in terms of surgical recovery and musculoskeletal function.
Therefore, it should be offered to respiratory-stable patients in
specialized centers.
Cobalt-Catalyzed Reductive Heck Cyclization Using Water as Hydrogen Donor to Access Oxindoles
Authors: Sun Li-Dong , Xiao Qian , Li Sanliang , Zhong Jian-Ji
Published: February 2025

An efficient cobalt-catalyzed intramolecular reductive Heck reaction using water as hydrogen donor for the synthesis of valuable 3,3-disubstituted oxindoles from 2-halo-N-arylacrylamides was described herein. Such an approach features operational simplicity and high functional group tolerance. Importantly, when the reaction was performed in D2O, the deuterated oxindoles could be rapidly accessed in a facile and low-cost manner.
Bioactive Molecules - via - Baylis-Hillman Chemistry
Authors: Jayathirtharao vaidya , Ch N.S. Sai Pavan Kumar
Published: February 2025

Abstract Baylis-Hillman chemistry is applied to make variety of new chemical entities for the purpose of evaluating them towards their bioactivity. Various substances synthesized via BH chemistry are subjected towards (i) antimalarial; (ii) anti-inflammatory; (iii) antidiabetic; (iv) antimicrobial; (v) anti tubercular; (vi) phosphodiesterase inhibitors; and (vii) anticancer activities. Couple of instances animal model and biology studies explored. Several hits and lead molecules are identified and their IC50 values listed. The simplicity of Baylis-Hillman chemistry provides a realistic evaluation towards pharma industries. The work presented on this subject will definitely have an impact over pharmaceutical companies.
Portal versus peripheral circulating tumor cells as prognostic biomarkers in patients with stage I-III pancreatic ductal adenocarcinoma
Authors: Prasoppokakorn Thaninee , Chaiteerakij Roongruedee , Buntho Areeya , Ingrungruanglert Praewphan , Israsena Nipan , Rittitid Wiriyaporn , Angsuwatcharakon Phonthep , Mekaroonkamol Parit , Kongkam Pradermchai , Rerknimitr Rungsun
Published: February 2025

Background: Portal venous circulating tumor cells (CTCs) detection may better reflect vascular metastasis and predict micro-metastasis risk in PDAC than peripheral blood. We hypothesize that portal CTCs could better represent micro-metastasis and predict survival in PDAC patients.
Methods: A single-center, prospective cohort study of patients with stage I-III PDAC was conducted. Portal venous blood was obtained via EUS-guided sampling, and peripheral blood was collected on the same day. CTCs were detected using EpCAM and mucin1 antibodies and reported as cells/8mL of blood.
Results: Among 35 patients, portal and peripheral CTC detection rates were 94.3% and 82.9%, respectively. Advanced PDAC with loco-regional metastasis had higher portal CTCs than less aggressive disease (p<0.05), while peripheral CTCs showed no significant differences. During the 50-month follow-up, patients with portal CTCs≥8 had poorer survival (6.1 vs. 19.0 months, p=0.001) and patients with peripheral CTCs≥3 also had poorer survival (4.6 vs. 14.2 months, p=0.002). In multivariable analysis, both portal CTCs≥8 and peripheral CTCs≥3 showed significant adjusted associations with survival (aHRs 3.39 and 2.71; p=0.009 and 0.020).
Conclusion: Higher CTC counts in both portal and peripheral systems were significantly associated with poorer survival in stage I-III PDAC; however, only portal CTCs reflected tumor aggression and loco-regional metastasis.
Impact of margin thermal ablation after cold-forceps avulsion with snare-tip soft coagulation for non-lifting large non-pedunculated colorectal polyps
Authors: Mandarino Francesco Vito , O'Sullivan Timothy , Gauci Julia Louisa , Kerrison Clarence , Whitfield Anthony , Lam Brian , Perananthan Varan , Gupta Sunil , Cronin Oliver , Medas Renato , Tate David J , Lee Eric Y , Burgess Nicholas G , Bourke Michael J.
Published: February 2025

Background and study aims: Non-lifting large non-pedunculated colorectal polyps (NL-LNPCPs) account for 15% of LNPCP and are effectively managed by Endoscopic Mucosal Resection with adjunctive Cold-forceps Avulsion with adjuvant Snare-Tip soft coagulation (CAST). However, recurrence rates > 10% at surveillance colonoscopy is a significant limitation. We aimed to compare the outcomes of CAST with MTA versus CAST alone for NL-LNPCPs.

Patient and methods: Prospective observational data on consecutive patients with NL-LNPCPs treated by EMR and CAST at a single tertiary center was retrospectively evaluated. Two cohorts were established: the pre-MTA period (January 2012-June 2017) and the MTA period (July 2017-October 2023). The primary outcome was the residual/recurrent adenoma (RRA) rate at first surveillance colonoscopy (SC1). Secondary outcomes included RRA at SC2 and adverse events.

Results: Over 142 months, 300 patients underwent EMR and CAST for LNPCP: 103 lesions pre-MTA and 197 with MTA.
At SC1 and SC2, recurrence was lower in the MTA cohort compared to the pre-MTA cohort (5.0% vs. 18.8%, p<0.001 and 0.8% vs. 10.0%, p<0.001, respectively).
Adverse events were similar between the two cohorts [deep mural injury types III-V (pre-MTA 2.9% vs MTA 5.6%, p=0.29), delayed bleeding (pre-MTA 8.7% vs MTA 7.1%, p=0.49)].
On multivariate analysis, MTA was the only variable independently associated with a reduced likelihood of recurrence (OR 0.20, 95% CI 0.07–0.54; P = 0.001).

Conclusions: For NL-LNPCPs, MTA in combination with CAST is safe and effective and reduces recurrence at SC1 in comparison to CAST alone.
Nonsurgical Periodontal Therapy Impacts Salivary and Serum Bone Turnover Markers in Periodontitis
Authors: Javed Faraha , Zia Afaf , Khan Asad Ullah , Bey Afsha , Hakim Seema , Ateeq Hira , Yusufi Faiz Noor Khan , Salati Nasir
Published: February 2025

Objectives To assess nonsurgical periodontal therapy's (NSPT's) effect on bone turnover markers (BTMs) in periodontitis patients and compare the efficacy of saliva and serum samples in evaluating periodontal health.

Materials and Methods Sixty-five females aged 18 to 45 years were divided into control (n = 20) and test (n = 45) groups. Periodontitis patients underwent NSPT. Full mouth clinical periodontal parameters and salivary/serum BTMs (C-terminal telopeptides of type I collagen [CTX], bone-specific alkaline phosphatase [BALP], osteoprotegerin [OPG]) were recorded at baseline, 3 weeks, and 3 months post-NSPT.

Statistical Analysis The study measured test group readings at three points: baseline, 3 weeks, and 3 months after NSPT. Normality was assessed using the Shapiro–Wilk test, showing a nonnormal distribution (p < 0.05). To test for significance among groups, the Kruskal–Wallis test was applied. The Friedman test, along with pairwise comparisons, was used to compare test group readings across time points. A 5% significance level was maintained. Pearson correlation measured relationships between the control and test groups and within the test group at different intervals. Multiple linear regression was conducted across time points, with plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL) set as dependent variables, and salivary and serum BALP, CTX, and OPG as independent variables. All analyses were performed using IBM SPSS version 20 and R version 3.5.2.

Results Following NSPT, significant changes were observed in all measured salivary/serum BTMs except serum BALP (p > 0.05). No significant differences noted between BTM measurements taken at 3 weeks and 3 months post-NSPT (p > 0.05). Correlations between BTMs and periodontal measurements were weak to moderate after NSPT. A multiple linear regression model explained 46.7% of the total variability for PI, 50.1% for PPD, 54.1% for CAL, and 29.3% for GI signifying association with BTMs among groups.

Conclusion NSPT results in significant changes in salivary/serum BTMs. Following NSPT, BTMs show associations with periodontal parameters, highlighting modulation of host responses. BTMs in salivary/serum samples effectively reflected periodontal health and disease status and improvements after therapy.
Effect of copper/tungsten heterophase interface on radiation resistance: insights from atomistic simulations
Authors: Chen Wen , Li Min , Fu Bao-Qin , Chen Tun , Cui Jie-Chao , Hou Qing
Published: February 2025

Nanostructured materials have demonstrated superior radiation-damage tolerance compared to their coarse-grained counterparts, contributing to the extended lifespan of nuclear materials. However, the mechanisms underlying this enhanced irradiation resistance remain unclear. In this study, we present atomistic simulations to investigate the impact of Cu/W heterophase interface on the evolution of irradiation-induced defects. The simulation results reveal that the Cu/W interfaces can act as defect sinks, effectively trapping self-interstitial atoms (SIAs). Furthermore, the interface demonstrates both the interstitial emission and interstitial transfer mechanisms, wherein the trapped W SIAs facilitate the emission of Cu atoms from the interface to the Cu side. These emitted Cu SIAs can promote defect recombination on the Cu side, leading to a reduced defect concentration in the Cu/W nano-multilayers. Consequently, these combined mechanisms contribute to a lower overall concentration of irradiation-induced defect, thereby enhancing the radiation resistance of Cu/W nano-multilayers.
Robust Quantum Gate Optimization with First-Order Derivatives of Ion-Phonon and Ion-Ion Coupling in Trapped Ions
Authors: Wang Jing-Bo
Published: February 2025

Trapped ion hardware has made significant progress recently and is now one of the leading platforms for quantum computing. To construct two-qubit gates in trapped ions, experimental manipulation approaches for ion chains are becoming increasingly prevalent. Given the restricted control technology, how implementing high-fidelity quantum gate operations is crucial. Many works in current pulse design optimization focus on ion-phonon and effective ion-ion coupling while ignoring the first-order derivatives terms expansion impacts of these two terms brought on by experiment defects. This paper proposes a novel robust quantum control optimization method in trapped ions. By introducing the first-order derivatives terms caused by the error into the optimization cost function, we generate an extremely robust Mølmer-Sørensen gate with infidelity below 10-3 under drift noise range ±10 kHz, the relative robustness achieves a tolerance of ±5%, compared to the 200 kHz frequency spacing between phonon modes, and for time noise drift, the tolerance reached to 2%. Our work reveals the vital role of the first-order derivatives terms of coupling in trapped ion pulse control optimization, especially the first-order derivatives terms of ion-ion coupling. It provides a robust optimization scheme for realizing more efficient entangled states in trapped ion platforms.
Molecular dynamics simulations of collision cascades in polycrystalline tungsten
Authors: Liu Lixia , Jiang Mingxuan , Gao Ning , Chen Yangchun , Hu Wangyu , Deng Hiuqiu
Published: February 2025

Using molecular dynamics methods, simulations of collision cascades in polycrystalline tungsten (W) have been conducted in this study, including different primary-knock-on atom (PKA) directions, grain sizes, and PKA energies between 10 and 150 keV. The results indicate that a smaller grain size leads to more defects forming in grain boundary regions during cascade processes. The impact of high-energy PKA may cause a certain degree of distortion of the grain boundaries, which has a higher probability in systems with smaller grain sizes and becomes more pronounced as the PKA energy increases. The direction of PKA can affect the formation and diffusion pathways of defects. When the PKA direction is perpendicular to the grain boundary, defects preferentially form near the grain boundary regions; by contrast, defects are more inclined to form in the interior of the grains. These results are of great significance for comprehending the changes in the performance of polycrystalline W under the high-energy fusion environments and can provide theoretical guidance for further optimization and application of W-based plasma materials.
Anomalous Hall effect in Bernal tetralayer graphene enhanced by spin-orbit interaction
Authors: Qu Zhuangzhuang , Chen Zhihao , Han Xiangyan , Wang Zhiyu , Li Zhuoxian , Liu Qianling , Zhao Wenjun , Watanabe Kenji , Taniguchi Takashi , Cheng Zhi Gang , Gan Zizhao , Lu Jianming
Published: February 2025

Spin-orbit interaction (SOI) can be introduced by the proximity effect to modulate the electronic properties of graphene-based heterostructures. In this work, we stacked trilayer WSe2 on Bernal tetralayer graphene to investigate the influence of SOI on anomalous Hall effect (AHE). In this structurally asymmetric device, by comparing the magnitude of AHE at positive and negative displacement fields, we find that AHE is strongly enhanced by bringing electrons in proximity to the WSe2 layer. Meanwhile, the enhanced AHE signal persists up to 80 K, providing important routes for topological device applications at high temperatures.
Everchanging range: how the changing environment has influenced the genetic diversity and differentiation of an iconic North American palm species
Authors: Klimova Anastasia , Landis Jacob
Published: February 2025

Background and Aims

Understanding spatial patterns of neutral and adaptive genetic variation and linking them to future climate change have become crucial in assessing the genetic vulnerability of species and developing conservation strategies. Using a combination of genomic approaches, this study aimed to explain the demographic history of Washingtonia palms, predict the adaptive potential in Washingtonia palm populations on the Baja California Peninsula (BCP) and southern California, and determine the geographical areas where climate change will have the most drastic effects.

Methods

We used over 5000 single nucleotide polymorphisms from 155 individuals across 18 populations spanning the entire distribution range of Washingtonia palms on the BCP and southern California. We examined past and current genetic diversity distribution patterns and identified outliers using genetic differentiation and genotype–environment association methods. Genetic vulnerability was predicted, and species distribution modelling was utilized for the geographical regions that will be at risk under future climate scenarios.

Key Results

Demographic modelling supported a bottleneck related to the Wisconsin glaciation, which was stronger and longer in northern Washingtonia populations. Genomic diversity presented a strong relationship to geography and provided evidence for range expansions from several refugia. Gradient Forest Analysis revealed that the genetic variation was shaped primarily by variables related to latitude and temperature during the coldest quarter, indicating adaptation to local thermal environments. We found limited adaptive potential and high levels of genetic vulnerability in lowland southern and central populations. Accordingly, species distribution modelling found that the southern distribution range will be affected by climate change, particularly under a high-emissions scenario.

Conclusions

Our findings include a history of population bottleneck related to postglacial range expansion, population divergence with limited gene flow, and probable future changes in distribution under changing conditions. Under long-term climate change, southern and central lowland populations of Washingtonia will experience harsher climate conditions and strong genomic offset.
Speeding up interval estimation for R2-based mediation effect of high-dimensional mediators via cross-fitting
Authors: Xu Zhichao , Li Chunlin , Chi Sunyi , Yang Tianzhong , Wei Peng
Published: February 2025

Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed iterative Sure Independence Screening (iSIS) in two subsamples to exclude the non-mediators, followed by ordinary least squares regressions for the variance estimation. We then constructed confidence intervals based on the newly derived closed-form asymptotic distribution of the R2 measure. Extensive simulation studies demonstrated that this proposed procedure is much more computationally efficient than the resampling-based method, with comparable coverage probability. Furthermore, when applied to the Framingham Heart Study, the proposed method replicated the established finding of gene expression mediating age-related variation in systolic blood pressure and identified the role of gene expression profiles in the relationship between sex and high-density lipoprotein cholesterol level. The proposed estimation procedure is implemented in R package CFR2M.
Co-occurrence of CT-based radiological sarcopenia and frailty are related to impaired survival in surgical oncology
Authors: Weerink Linda B M , van Leeuwen Barbara L , Kwee Thomas C , Lamoth Claudine J C , van Munster Barbara C , de Bock Geertruida H
Published: February 2025

Objectives

The objective of this study was to investigate the association of radiological sarcopenia and frailty with postoperative outcomes in adult patients undergoing oncological surgery.

Methods

Data were derived from the PICNIC study, consisting of two consecutive series of patients undergoing surgical cancer treatment. Radiological sarcopenia was assessed based on CT imaging. The presence of low muscle mass and/or low muscle density was determined based on lowest quartile gender specific cut-off values. Frailty was defined by a score of ≥4 on the Groningen frailty index. Postoperative overall survival was analysed with Kaplan-Meier curves and Logrank testing. Multivariable Cox regression analyses adjusted for age and gender were performed to calculate adjusted hazard ratios (HR).

Results

A total of 372 patients were included. Median age was 69 (28-86) years, 77 patients (23.5%) were frail and radiological sarcopenia was present in 134 patients (41.0%). Combined radiological sarcopenia and frailty was present in 35 patients (10.7%). One-year (65.6% versus 87.0%) and three-year survival (31.4% versus 66.8%) were significantly worse in patients with combined radiological sarcopenia and frailty. The combined presence of radiological sarcopenia and frailty was associated with significantly decreased overall survival (HRadjusted: 2.06, 95% CI: 1.39-3.05, P < .001).

Conclusion

Co-occurrence of radiological sarcopenia and frailty is strongly related to impaired survival in surgical cancer patients.

Advances in knowledge

The combined presence of radiological sarcopenia and frailty is associated with decreased postoperative survival, strongly exceeding the effects of both risk factors separately. The use of radiological sarcopenia in addition to frailty screening can further optimize preoperative risk stratification.
Navigating neural pathways: how stimulation polarity shapes deep brain stimulation efficacy
Authors: Asadi Atefeh , Koirala Nabin , Muthuraman Muthuraman
Published: February 2025

This scientific commentary refers to ‘Neural pathway activation in the subthalamic region depends on stimulation polarity’ by Borgheai et al. (https://doi.org/10.1093/braincomms/fcaf006).
Modulating nociception networks: the impact of low-intensity focused ultrasound on thalamocortical connectivity
Authors: Mishra Arabinda , Yang Pai-Feng , Manuel Thomas J , Newton Allen T , Phipps M Anthony , Luo Huiwen , Sigona Michelle K , Dockum Allison Q , Reed Jamie L , Gore John C , Grissom William A , Caskey Charles F , Chen Li Min
Published: February 2025

Pain engages multiple brain networks, with the thalamus serving as a critical subcortical hub. This study aims to explore the effects of low-intensity transcranial focused ultrasound (FUS) induced suppression on the organization of thalamocortical nociceptive networks. We employed MR-guided focused ultrasound (MRgFUS), a potential non-invasive therapy, with real-time ultrasound beam localization feedback and fMRI monitoring. We first functionally identified the focused ultrasound target at the thalamic ventroposterior lateral nucleus by mapping the whole brain blood oxygenation level-dependent responses to nociceptive heat stimulation of the hand using fMRI in each individual macaque monkey under light anesthesia. The blood oxygenation level-dependent fMRI signals from the heat-responsive thalamic ventroposterior lateral nucleus were analyzed to derive thalamocortical effective functional connectivity network using the psychophysical interaction method. Nineteen cortical regions across sensorimotor, cognitive, associative, and limbic networks exhibited strong effective functional connectivity to the thalamic ventroposterior lateral during heat nociceptive processing. Focused ultrasound-induced suppression of heat activity in the thalamic VPL altered nociceptive responses in most of the nineteen regions. Data-driven hierarchical clustering analyses of blood oxygenation level-dependent time courses across all thalamocortical ROI pairs identified two effective functional connectivity subnetworks. The concurrent suppression of thalamic heat response with focused ultrasound reorganized these subnetworks and modified thalamocortical connection strength. Our findings suggest that the thalamic ventroposterior lateral nucleus has extensive and causal connections to a wide array of cortical areas during nociceptive processing. The combination of MRgFUS with fMRI enables precise dissection and modulation of nociceptive networks in the brain, a capability that no other device-based neuromodulation methods have achieved. This presents a promising non-invasive tool for modulating pain networks with profound clinical relevance. The robust modulation of nociceptive effective functional connectivity networks by focused ultrasound strongly supports the thalamic ventroposterior lateral as a viable target for pain management strategies.
Photoinduced synthesis of ultrafine Pt nanoparticles loaded on the surface of MOFs-modified carbon materials for efficient catalytic reduction reactions
Authors: Xian Liang , Tian Xiaoxia , Liu Zhaomin , Liu Shuxin , Zhao Jiuzhou
Published: February 2025

In this paper, ultrafine platinum nanoparticles (Pt/Co-N-C) were prepared by irradiating the mixture of Co-N-C and K2[PtCl4] with near-ultraviolet (UV) light at a wavelength of 395 nm and visible light at 450 and 550 nm without adding any reducing and stabilizing agents using MOFs-modified carbon materials (Co-N-C) as the carrier. The composition and morphology of the Pt/Co-N-C catalysts were investigated using characterization tools such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and high-resolution transmission electron microscopy (HR-TEM), etc. The results showed that the Pt nanoparticles were well dispersed on the surface of the Co-N-C, with average particle sizes of about 2.39, 2.86, and 3.53 nm, respectively. In the catalytic 4-NP reduction experiments, the catalyst (Pt/Co-N-C-1) prepared under near-ultraviolet light (395 nm) irradiation showed the highest catalytic activity with a rate constant k=0.64 min-1. After five cycles, the conversion rate was still maintained at about 90%, which was highly reusable. It was demonstrated that 395 nm near-ultraviolet light was more favorable for the modulation of the distribution of the species during the hydrolysis and reduction of platinum in this reaction to form smaller-sized platinum nanocrystals, which was conducive to the catalyst to exhibit higher activity.
Clinical relevance of Thiopurine methyl transferase genotype testing for azathioprine in dermatology
Authors: Ramassamy Sivaranjini , Chandrashekar Laxmisha , Mathaiyan Jayanthi , Rajappa Medha , Devanathan Reka , Selvarathinam Sujeevan , Goud Alladi Charanraj
Published: February 2025

Background

Polymorphisms in thiopurine methyltransferase (TPMT) are a predominant cause of azathiopurine-induced leukopenia in the Western countries. The exact role of these polymorphisms in Indian population with dermatological disorders is uncertain.

Methods

We included consecutive patients on Azathioprine who were initiated for dermatological disorders from south India. Three TPMT polymorphisms (c.238 G > C, c.460 G > A, and c.719A > G) were assessed. A comparison of the proportion of adverse events to azathioprine, especially myelosuppression, was performed between those with wild-type genotype and those with TPMT polymorphisms.

Results

Of the 123 patients (61 males, mean age 46 years), 65% had autoimmune blistering disorder. Adverse event to azathioprine was noted in 25 (20.3%), of which 16 (13%) had myelosuppression, four (3.2%) each had hepatotoxicity and gastrointestinal intolerance. TPMT polymorphisms were detected amongst 13 (10.7%), of which five had experienced adverse events. The polymorphisms could explain 25% (4 out of 16) of the cases of leucopenia. The odds of developing leukopenia in TPMT polymorphism was not significant (3.63, 95% CI 0.96-13.60, p=0.055).

Conclusion

The tested TPMT polymorphisms could not predict the adverse events, particularly the haematological toxicity of azathioprine in dermatological use among the south Indian population.
Yellow Firm Papules on Bilateral Lower Extremities: A Clinicopathological Challenge
Authors: Arora Neha , Leszczynska Maria , Preston Allie , Furukawa Betsy
Published: February 2025

Miliarial gout is a rare presentation of disseminated tophaceous gout mimicking milia-like papules. This case describes the rare entity of miliarial gout and illustrates the importance of recognizing an atypical dermatologic manifestation of chronic gout.
KDM1A genetic alterations, a rare cause of primary bilateral macronodular adrenal hyperplasia, strongly associated with food-dependent Cushing's syndrome: results of its systematic germline screening in 301 index cases and genotype/phenotype correlation
Authors: Bouys Lucas , Vaduva Patricia , Jouinot Anne , Violon Florian , Vaczlavik Anna , Barat Maxime , Charchar Helaine , Chasseloup Fanny , Kamilaris Crystal , Espiard Stéphanie , Haissaguerre Magalie , Raverot Gérald , Kroiss Matthias , Berthon Annabel , Perlemoine Karine , Tauveron Igor , Guignat Laurence , Libé Rossella , Groussin Lionel , Assié Guillaume , Pasmant Eric , Reincke Martin , Borson-Chazot Françoise , Ferrière Amandine , Vantyghem Marie-Christine , Stratakis Constantine A , Kamenický Peter , Fragoso Maria Candida Barisson Villares , Chansavang Albain , Ragazzon Bruno , Bertherat Jérôme
Published: February 2025

Objective

ARMC5 is the most prevalent gene predisposing to primary bilateral macronodular adrenal hyperplasia (PBMAH), but germline KDM1A variants have been identified in the rare PBMAH associated with food-dependent Cushing's syndrome (FDCS). The purpose of this work was to assess the frequency of KDM1A variants in a large series of PBMAH patients.

Design

A total of 301 consecutive PBMAH index cases from 8 international endocrinology departments were included. Clinical, biological, and imaging data were collected retrospectively.

Results

Ten (3.3%) patients carried a germline KDM1A pathogenic or likely pathogenic variant, 60 (19.9%) carried a germline ARMC5 alteration, and 231 (76.8%) had no identified genetic predisposition. Food-dependent Cushing's syndrome was present in all patients with KDM1A variants and absent in the 2 other groups. KDM1A patients had a higher 24-h urinary free cortisol (3.0-fold upper limit of normal vs 1.36 for ARMC5 patients and 0.66 for wild-type patients, respectively, P = .0001). In accordance with FDCS pathophysiology, patients with KDM1A variants had a lower morning fasting plasma cortisol (192 nmol/L vs 407 and 428, respectively, P = .0003) and a higher midnight plasma cortisol (487 nmol/L vs 297 and 171.96, respectively, P = .0004). Morning/midnight plasma cortisol ratio below 0.65 holds 100% sensitivity and specificity for the detection of FDCS. All patients with KDM1A variants were women, vs 65% of ARMC5 patients and 67% of wild-type patients (P = .0337).

Conclusions

KDM1A germline pathogenic variants are rare in PBMAH and account for <5% of index cases. KDM1A seems constantly associated with FDCS, which can be evoked in front of a morning/midnight plasma cortisol ratio below 0.65.
Reference equations for peak oxygen uptake for treadmill cardiopulmonary exercise tests based on the NHANES lean body mass equations, a FRIEND registry study
Authors: Santana Everton J , Kim Daniel Seung , Christle Jeffrey W , Cauwenberghs Nicholas , Celestin Bettia E , Tso Jason V , Wheeler Matthew T , Ashley Euan A , Peterman James E , Gardner Christopher , Arena Ross , Harber Matthew , Kaminsky Leonard A , Kuznetsova Tatiana , Myers Jonathan N , Haddad Francois
Published: February 2025

Aims

Cardiorespiratory fitness (CRF), measured by peak oxygen uptake (VO2peak), is a strong predictor of mortality. Despite its widespread clinical use, current reference equations for VO2peak show distorted calibration in obese individuals. Using data from the Fitness Registry and the Importance of Exercise National Database (FRIEND), we sought to develop novel reference equations for VO2peak better calibrated for overweight/obese individuals - in both males and females, by considering body composition metrics.

Methods

Graded treadmill tests from 6,836 apparently healthy individuals were considered in data analysis. We used the National Health and Nutrition Examination Survey equations to estimate lean body mass (eLBM) and body fat percentage (eBF). Multivariable regression was used to determine sex-specific equations for predicting VO2peak considering age terms, eLBM and eBF.

Results

The resultant equations were expressed as VO2peak (male) = 2633.4 + 48.7✕eLBM (kg) - 63.6✕eBF (%) - 0.23✕Age2 (R2=0.44) and VO2peak (female) = 1174.9 + 49.4✕eLBM (kg) - 21.7✕eBF (%) - 0.158✕Age2 (R2=0.53). These equations were well-calibrated in subgroups based on sex, age and body mass index (BMI), in contrast to the Wasserman equation. In addition, residuals for the percent-predicted VO2peak (ppVO2) were stable over the predicted VO2peak range, with low CRF defined as < 70% ppVO2 and average CRF defined between 85-115%.

Conclusions

The derived VO2peak reference equations provided physiologically explainable and were well-calibrated across the spectrum of age, sex and BMI. These equations will yield more accurate VO2peak evaluation, particularly in obese individuals.
Depletion of mitochondrial CypD in endothelial and smooth muscle cells attenuates vascular dysfunction and hypertension
Authors: Dikalova Anna , Ao Mingfang , Lantier Louise , Gutor Sergey , Dikalov Sergey
Published: February 2025

Hypertension is a major risk factor of cardiovascular disease affecting nearly half of adult population, but only 25% patients have their blood pressure under control. Hypertension is associated with mitochondrial dysfunction; however, its molecular mechanisms and causative role are still elusive. Understanding these mechanisms is important to develop new therapies. Cyclophilin D (CypD) promotes mitochondrial swelling and dysfunction. The objective of this study is to test if CypD depletion attenuates vascular dysfunction and hypertension. To test this hypothesis, we used endothelial-specific and smooth muscle-specific CypD knockout mice in angiotensin II model of vascular dysfunction and hypertension. Our results show that depletion of endothelial CypD prevents angiotensin II-induced impairment of endothelial-dependent vasorelaxation, preserves endothelial nitric oxide and mitochondrial respiration, reduces hypertension, vascular oxidative stress and vascular metabolic glycolytic-switch compared with wild-type littermates. Depletion of smooth muscle CypD slightly reduces angiotensin II-induced hypertension, partially attenuates reduction in vascular nitric oxide and vasorelaxation, abolishes vascular superoxide overproduction, diminishes angiotensin II-induced vascular glycolysis, hypertrophy and fibrosis. Our data showed an intriguing “metabolic” and “redox” crosstalk between endothelial and smooth muscle cells. Depletion of endothelial CypD reduces not only angiotensin II-induced endothelial glycolysis but also attenuates smooth muscle cell glycolytic switch. Interestingly, depletion of smooth muscle CypD was also not limited to the effect on smooth muscle glycolysis, but it also reduced endothelial cell glycolysis. Vascular oxidative stress was inhibited both in EcCypDKO and SmcCypDKO mice, therefore, cell-specific CypD depletion had a “global” antioxidant effect on the entire vasculature. Our results support a novel function of mitochondrial CypD in regulation of superoxide production and metabolism of vascular smooth muscle and endothelial cells which affect endothelial barrier and smooth muscle vascular functions. We suggest that blocking vascular CypD reduces vascular oxidative stress, improves vascular metabolism and vascular function which may be beneficial in cardiovascular disease.
Loneliness as a risk factor for time to care home entry for older adults receiving community care
Authors: Rickman Sam , Fernandez Jose-Luis , Malley Juliette
Published: February 2025

Background and Objectives

International efforts to contain long-term care costs have prioritised personal care. However, reductions in services aimed at addressing loneliness or promoting social participation may affect demand for long-term care facilities. Research on the impact of loneliness on entry to residential or nursing care is based on survey data, which under-represents those with highest needs. Administrative records include such individuals and, unlike surveys, contain continuous data on service receipt, enabling accurate modelling of time to care home entry.

Research Design and Methods

We use administrative data for 1,101 individuals receiving care in a London local authority. We extract loneliness from free text notes using a large language model and model its impact on care home entry five years after assessment, controlling for needs and demographics. We use logistic regression and a competing risks survival model to measure time until care home entry.

Results

The odds ratio for care home entry associated with loneliness is 1.45 with logistic regression (95% CI 1.04 – 2.01). The hazard ratio is 1.32 (95% CI 1.01 – 1.72) with a cause-specific model, and 1.39 (95% CI 1.08 - 1.79) using the Fine & Gray method. Among those most likely to enter a care home, the median time to entry is 9 months (95% CI 228 - 328 days) earlier for those who are lonely.

Discussion and Implications

The hazard ratio of loneliness on care home entry is around the magnitude associated with gender, ethnicity or living alone. However, loneliness is modifiable. Reductions to services for social participation, such as day centres, are likely to cause an increase in loneliness. We demonstrate that for those with the highest needs, loneliness is a significant risk factor for time until care home entry. Policymakers seeking to delay care home entry should consider the impact of services for loneliness.
Pilot Randomized Controlled Trial of the Feasibility of a Mobile App-Delivered Mindfulness-Based Intervention for Caregiver Stress
Authors: Plys Evan , Seward Morgan , Allen Elizabeth M , Tatar Raquel G , Huberty Jennifer , Vranceanu Ana-Maria
Published: February 2025

Background and Objectives

We tested feasibility and preliminary benefits of a free mobile app-delivered mindfulness-based intervention for stress among dementia caregivers (i.e., Healthy Minds Program for Caregivers [HMP-C]).

Research Design and Methods

Single-blind Stage 1b pilot randomized controlled trial compared 12 weeks of HMP-C (n = 47) with a dose-matched education podcast control (n = 48; Wellness App [WA]). T-tests examined between-group differences.

Results

Feasibility benchmarks were met for acceptability (90% eligible enrolled), demand (95% completed post-tests), and data collection (100% measures complete). Treatment satisfaction was sufficient for HMP-C. Adherence was lower than benchmarks (>52.5 minutes weekly) for HMP-C (57%) and WA (59%). Mechanistic targets of mindfulness (p < .001; d = -1.21) and positive aspects of caregiving (p < .001; d = -0.92) showed large pre-post improvements in the HMP-C group. Mechanistic validity was established through significant correlations between change in stress and change in mindfulness (r =-.40, p =.006) and positive aspects of caregiving (r =-.49, p =.001). Pre-post improvements in HMP-C were not statistically significantly compared with WA for stress (p = .097; d = -0.35), depression (p = .110; d = -0.34), or anxiety (p = .237; d = -0.25).

Discussion and Implications

The current study demonstrated feasibility and mechanistic target engagement and validity for HMP-C. As expected in an underpowered feasibility trial, clinical outcomes did not improve more than control, but trends favored HMP-C. Together, findings demonstrate that a fully powered Stage 2 trial is warranted to test the efficacy of HMP-C compared with WA.
An analytical form of the pore-emanating crack model in 3-D with implications for the uniaxial compressive strength of sandstone
Authors: Wadsworth Fabian B , Vasseur Jérémie , Heap Michael J
Published: February 2025

The uniaxial compressive strength ${\sigma _c}$ of rocks is a key material property in a wide range of applications. Models for ${\sigma _c}$ typically either require numerical solutions, restricting their wide utility, or are empirical and therefore confined to a specific case. Here, we study the theoretical pore-emanated crack model and provide an analytical emulator function that matches the 2-D and 3-D solutions to a high degree of accuracy over all porosities, $\phi $. A key input to both the full solution and to our emulator functions is the pore radius, assumed in the model to be circular or spherical, in a porous rock. In most porous lithologies, including sandstone, the notion of a pore radius is poorly defined since they are built from compacted or lithified grains. And so here we explore statistical methods to find a characteristic pore length scale, ${l_2}$, from an initial particle radius; this method is provided as an easy-to-use supplementary tool. We advocate for the use of our 3-D function ${\sigma _c} \approx 1.57{K_{{\bf{Ic}}}}/( {{\phi ^{0.43}}\sqrt {\pi {l_2}} } )$, where ${K_{{\bf{Ic}}}}$ is the fracture toughness of the solid matrix. A compilation of ${K_{{\bf{Ic}}}}$ values for minerals and rocks allows us to explore the effect of this parameter and to make recommendations for appropriate values in the model. We compare our simple emulator function for ${\sigma _c}$ with existing data sets across a wide range of sandstones to demonstrate the utility of this law for applied cases. We find that our function performs particularly well for relatively low porosity sandstones ($\phi \mathbin{\lower.3ex\hbox{$\buildrel<\over {\smash{\scriptstyle\sim}\vphantom{_x}}$}} 0.15$) representative of mature basin systems from a diagenetic point of view; we discuss alternative models that are more appropriate for higher porosity sandstones.
Comparison of the functional properties between tapioca resistant maltodextrin and commercial prebiotics
Authors: Namkieat Pichamon , Borompichaichartkul Chaleeda , Phumsombat Putthapong , Ayuni Dwi , Sapwarobol Suwimol
Published: February 2025

This study examined the prebiotic potential of tapioca resistant maltodextrin (TRM), a novel non-viscous, soluble resistant starch, and compared it to commercial prebiotics (inulin, fructooligosaccharides (FOS), and konjac glucomannan hydrolysate (KGMH). This is the first study to reveal the prebiotic activity of TRM compared to commercial prebiotics. The prebiotic activity score (PAS) was used to measure a prebiotic’s ability to promote probiotic growth and inhibit pathogens. Probiotic strains, including Lactobacillus acidophilus DDS-1®, Lactobacillus rhamnosus LGG®, Lactobacillus salivarius B37, Lactobacillus paracasei 431®, Bifidobacterium longum UABI-14, and Bifidobacterium breve M16V, along with the pathogen Escherichia coli ATCC 25922, were cultured in media supplemented with 1% inulin, FOS, KGMH, TRM, or glucose. Cultures were incubated at 37 °C for 72 hours, with bacterial counts and pH levels measured at baseline and after 12, 24, 48, and 72 h. Viable cell counts after simulated gastrointestinal digestion were also assessed. Our results showed that TRM had the highest PAS for L. rhamnosus LGG® at 24 and 72 hours and L. salivarius B37 at 48 h. Bifidobacterium strains showed no significant differences in PAS between TRM and other prebiotics. TRM demonstrated high viability for L. salivarius B37 and L. paracasei 431® after digestion, suggesting its potential use as a prebiotic.
Development of chickpea beverages through enzymatic treatments: from rapid visco analyzer to pilot plant production
Authors: Ruiz-Zambrano Nidia Leticia , Gasparre Nicola , Pérez-Carrillo Esther , Rosell Cristina M
Published: February 2025

Plant-based beverage production generally involves enzymatic treatments to overcome technological challenges. Thus, this research aimed to evaluate the potential use of the Rapid Visco Analyser (RVA) to simulate pilot plant (PP) conditions and determine the enzyme(s) and enzyme-concentrations to be used in PP for beverage production using chickpea flour. α-Amylase-TA, maltogenase-MA and amyloglucosidase-AMG were tested individually and in combination at three concentrations. Chickpea suspensions with 3% protein, equivalent to milk contribution, were produced at laboratory scale in RVA while simulating PP. Highest viscosity reductions was obtained with the highest enzymatic activity (TA.3 = 1.21 CU/g flour; MA.3 = 0.15 CU/g flour; AMG.3 = 0.69 mg of glucose released/g flour). TA was the most effective in reducing final viscosity and increasing free sugars, particularly combined with TA + MA + AMG. RVA findings were validated in PP-production using TA.3 + MA.3 + AMG.3. Viscosity decreased from 50,697 ± 8,907 cP observed in the control to 4,505 ± 171 cP when using TA.3 + MA.3 + AMG.3. Due to homogenization, the whiteness index was higher for PP beverages (67–71) than for RVA suspensions (65–67). This study demonstrates the potential of using RVA as a tool to optimize enzyme concentrations for chickpea beverage production and the successful scale-up of the process to PP-level.