bluuebunny/crossref_metadata_2025 huggingface dataset:
The CARING study: Examining biological, behavioral, and genetic mechanisms in the intergenerational transmission of toxic stress
Authors: Condon Eileen M. , Scheibner Hannah R. , Kuzel Meredith , Howard Mackenzie , Cisse Mouhamadou , O'Connell Meghan , Conley Yvette , Jeon Sangchoon , Sadler Lois S. , Redeker Nancy S.
Published: May 2024

When children experience extreme or persistent stressors (e.g., maltreatment, housing insecurity, intimate partner violence), prolonged elevation of the stress‐response system can lead to disrupted development of multiple physiological systems. This response, known as toxic stress, is associated with poor physical and mental health across the life course. Emerging evidence suggests that the effects of toxic stress may be transmitted through generations, but the biological and behavioral mechanisms that link caregivers’ childhood history with the health of the children they care for remain poorly understood. The purpose of this report is to describe the research protocol for The CARING (Childhood Adversity and Resilience In the Next Generation) Study, a cross‐sectional study of caregivers with children aged 3–5 years designed to (1) examine the intergenerational transmission of toxic stress and protective factors; (2) explore three hypothesized pathways of transmission: parenting, daily routines, stressors, and supports; and (3) explore the extent to which genotypic variation in candidate genes related to caregiving and stress contribute to caregivers’ and children's susceptibility to the effects of early childhood experiences (i.e., gene × environment interactions). We expect that findings from this study will provide critical data needed to identify targets for precision health interventions, reduce health disparities related to toxic stress, and prevent cycles of adversity among families at risk.
PCDHGC3 hypermethylation as a potential biomarker of intestinal neuroendocrine carcinomas
Authors: Cubiella Tamara , Celada Lucía , San‐Juan‐Guardado Jaime , Rodríguez‐Aguilar Raúl , Suárez‐Priede Álvaro , Poch María , Dominguez Francisco , Fernández‐Vega Iván , Montero‐Pavón Pedro , Fraga Mario F , Nakatani Yoichiro , Takata So , Yachida Shinichi , Valdés Nuria , Chiara María‐Dolores
Published: May 2024

Neuroendocrine neoplasms (NENs) encompass tumors arising from neuroendocrine cells in various organs, including the gastrointestinal tract, pancreas, adrenal gland, and paraganglia. Despite advancements, accurately predicting the aggressiveness of gastroenteropancreatic (GEP) NENs based solely on pathological data remains challenging, thereby limiting optimal clinical management. Our previous research unveiled a crucial link between hypermethylation of the protocadherin PCDHGC3 gene and neuroendocrine tumors originating from the paraganglia and adrenal medulla. This epigenetic alteration was associated with increased metastatic potential and succinate dehydrogenase complex (SDH) dysfunction. Expanding upon this discovery, the current study explored PCDHGC3 gene methylation within the context of GEP‐NENs in a cohort comprising 34 cases. We uncovered promoter hypermethylation of PCDHGC3 in 29% of GEP‐NENs, with a significantly higher prevalence in gastrointestinal (GI) neuroendocrine carcinomas (NECs) compared with both pancreatic (Pan) NECs and neuroendocrine tumors (NETs) of GI and Pan origin. Importantly, these findings were validated in one of the largest multi‐center GEP‐NEN cohorts. Mechanistic analysis revealed that PCDHGC3 hypermethylation was not associated with SDH mutations or protein loss, indicating an SDH‐independent epigenetic mechanism. Clinically, PCDHGC3 hypermethylation emerged as a significant prognostic factor, correlating with reduced overall survival rates in both patient cohorts. Significantly, whereas PCDHGC3 hypermethylation exhibited a strong correlation with TP53 somatic mutations, a hallmark of NEC, its predictive value surpassed that of TP53 mutations, with an area under the curve (AUC) of 0.95 (95% CI 0.83–1.0) for discriminating GI‐NECs from GI‐NETs, highlighting its superior predictive performance. In conclusion, our findings position PCDHGC3 methylation status as a promising molecular biomarker for effectively stratifying patients with GI‐NENs. This discovery has the potential to advance patient care by enabling more precise risk assessments and tailored treatment strategies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Vancomycin: An analysis and evaluation of eight population pharmacokinetic models for clinical application in general adult population
Authors: Duong Alexandre , El Gamal Ahmed , Bilodeau Véronique , Huot Justine , Delorme Carole , Poudrette Johanne , Crevier Benoît , Marsot Amélie
Published: May 2024

Introduction

Based on the recent guidelines for vancomycin therapeutic drug monitoring (TDM), the area under the curve to minimum inhibitory concentration ratio was to be employed combined with the usage of population pharmacokinetic (popPK) model for dosing adaptation. Yet, deploying these models in a clinical setting requires an external evaluation of their performance.

Objectives

This study aimed to evaluate existing vancomycin popPK models from the literature for the use in TDM within the general patient population in a clinical setting.

Methods

The models under external evaluation were chosen based on a review of literature covering vancomycin popPK models developed in general adult populations. Patients' data were collected from Charles‐Le Moyne Hospital (CLMH). The external evaluation was performed with NONMEM® (v7.5). Additional analyses such as evaluating the impact of number of samples on external evaluation, Bayesian forecasting, and a priori dosing regimen simulations were performed on the best performing model.

Results

Eight popPK models were evaluated with an independent dataset that included 40 patients and 252 samples. The model developed by Goti and colleagues demonstrated superior performance in diagnostic plots and population predictive performance, with bias and inaccuracy values of 0.251% and 22.7%, respectively, and for individual predictive performance, bias and inaccuracy were −4.90% and 12.1%, respectively. When limiting the independent dataset to one or two samples per patient, the Goti model exhibited inadequate predictive performance for inaccuracy, with values exceeding 30%. Moreover, the Goti model is suitable for Bayesian forecasting with at least two samples as prior for the prediction of the next trough concentration. Furthermore, the vancomycin dosing regimen that would maximize therapeutic targets of area under the curve to minimum inhibitory concentration ratio (AUC24/MIC) and trough concentrations (Ctrough) for the Goti model was 20 mg/kg/dose twice daily.

Conclusion

Considering the superior predictive performance and potential for Bayesian forecasting in the Goti model, future research aims to test its applicability in clinical settings at CLMH, both in a priori and a posteriori scenario.
Prediction of peptide hormones using an ensemble of machine learning and similarity‐based methods
Authors: Kaur Dashleen , Arora Akanksha , Vigneshwar Palani , Raghava Gajendra P. S.
Published: May 2024

Peptide hormones serve as genome‐encoded signal transduction molecules that play essential roles in multicellular organisms, and their dysregulation can lead to various health problems. In this study, we propose a method for predicting hormonal peptides with high accuracy. The dataset used for training, testing, and evaluating our models consisted of 1174 hormonal and 1174 non‐hormonal peptide sequences. Initially, we developed similarity‐based methods utilizing BLAST and MERCI software. Although these similarity‐based methods provided a high probability of correct prediction, they had limitations, such as no hits or prediction of limited sequences. To overcome these limitations, we further developed machine and deep learning‐based models. Our logistic regression‐based model achieved a maximum AUROC of 0.93 with an accuracy of 86% on an independent/validation dataset. To harness the power of similarity‐based and machine learning‐based models, we developed an ensemble method that achieved an AUROC of 0.96 with an accuracy of 89.79% and a Matthews correlation coefficient (MCC) of 0.8 on the validation set. To facilitate researchers in predicting and designing hormone peptides, we developed a web‐based server called HOPPred. This server offers a unique feature that allows the identification of hormone‐associated motifs within hormone peptides. The server can be accessed at: https://webs.iiitd.edu.in/raghava/hoppred/.
Comparison of home‐based spirometry and oscillometry measurements in school‐age children with bronchopulmonary dysplasia
Authors: Lee Julia X. , Ryan Morgan , Mukharesh Lana , Dahlberg Suzanne E. , Sun Bob Z. , Hayden Lystra , Phipatanakul Wanda , Gaffin Jonathan
Published: May 2024

Introduction

This study compares home‐based oscillometry and spirometry for characterizing respiratory system disease in school‐aged children with bronchopulmonary dysplasia (BPD) in clinical research. We hypothesized higher rates of successful completion and abnormal cases identified through oscillometry, with correlations between device measurements.

Methods

Participants 6–12 years old with BPD in the ongoing Air Quality, Environment and Respiratory Outcomes in BPD (AERO‐BPD) study performed oscillometry followed by spirometry at two separate home visits. Parameters measured included airway resistance at 5 Hz(R5), resistance from 5 to 19 Hz(R5‐19), resonance frequency(Fres), reactance at 5 Hz(X5), area under the curve between Fres and X5(AX), forced expiratory volume in 1 second(FEV1), forced vital capacity(FVC), and FEV1/FVC. Descriptive statistics identified the proportion of successful tests, correlation in measurements, and rate of lung disease for each device.

Results

Among 76 subjects with 120 paired observations, 95% and 71% of participants successfully performed oscillometry and spirometry, respectively, at home visit one. 98% and 77% successfully performed oscillometry and spirometry, respectively, at home visit two. Odds ratios favored oscillometry (range 5.31–10.13, p < 0.01). FEV1 correlated with AX (correlation coefficient r = −0.27, p = 0.03); FEV1/FVC with AX (r = −0.32, p = 0.02); and FEV1/FVC with R5 (r = −0.37, p = 0.01). AX exhibited the highest prevalence of abnormality at 25%; other oscillometry parameters ranged from 5%–22%. Forty‐five to sixty‐four percent of participants had abnormal spirometry. Oscillometry assessments had significantly lower odds of capturing lung disease (odds ratios 0.07–0.24, p < 0.0001).

Conclusions

School‐aged children with BPD demonstrated higher success rates in field‐based oscillometry than spirometry. Spirometry exhibited higher rates of abnormality than oscillometry. Moderate correlation exists between device measurements.
Invariant point message passing for protein side chain packing
Authors: Randolph Nicholas Z. , Kuhlman Brian
Published: May 2024

Protein side chain packing (PSCP) is a fundamental problem in the field of protein engineering, as high‐confidence and low‐energy conformations of amino acid side chains are crucial for understanding (and designing) protein folding, protein–protein interactions, and protein‐ligand interactions. Traditional PSCP methods (such as the Rosetta Packer) often rely on a library of discrete side chain conformations, or rotamers, and a forcefield to guide the structure to low‐energy conformations. Recently, deep learning (DL) based methods (such as DLPacker, AttnPacker, and DiffPack) have demonstrated state‐of‐the‐art predictions and speed in the PSCP task. Building off the success of geometric graph neural networks for protein modeling, we present the Protein Invariant Point Packer (PIPPack) which effectively processes local structural and sequence information to produce realistic, idealized side chain coordinates using ‐angle distribution predictions and geometry‐aware invariant point message passing (IPMP). On a test set of ∼1400 high‐quality protein chains, PIPPack is highly competitive with other state‐of‐the‐art PSCP methods in rotamer recovery and per‐residue RMSD but is significantly faster.
ERegPose: An explicit regression based 6D pose estimation for snake‐like wrist‐type surgical instruments
Authors: Li Jinhua , Ma Zhengyang , Sun Xinan , Su He
Published: May 2024

Background

Accurately estimating the 6D pose of snake‐like wrist‐type surgical instruments is challenging due to their complex kinematics and flexible design.

Methods

We propose ERegPose, a comprehensive strategy for precise 6D pose estimation. The strategy consists of two components: ERegPoseNet, an original deep neural network model designed for explicit regression of the instrument's 6D pose, and an annotated in‐house dataset of simulated surgical operations. To capture rotational features, we employ an Single Shot multibox Detector (SSD)‐like detector to generate bounding boxes of the instrument tip.

Results

ERegPoseNet achieves an error of 1.056 mm in 3D translation, 0.073 rad in 3D rotation, and an average distance (ADD) metric of 3.974 mm, indicating an overall spatial transformation error. The necessity of the SSD‐like detector and L1 loss is validated through experiments.

Conclusions

ERegPose outperforms existing approaches, providing accurate 6D pose estimation for snake‐like wrist‐type surgical instruments. Its practical applications in various surgical tasks hold great promise.
Challenges and opportunities in piezoelectric polymers: Effect of oriented amorphous fraction in ferroelectric semicrystalline polymers
Authors: Rui Guanchun , Allahyarov Elshad , Zhu Zhiwen , Huang Yanfei , Wongwirat Thumawadee , Zou Qin , Taylor Philip L. , Zhu Lei
Published: May 2024

Despite extensive research on piezoelectric polymers since the discovery of piezoelectric poly(vinylidene fluoride) (PVDF) in 1969, the fundamental physics of polymer piezoelectricity has remained elusive. Based on the classic principle of piezoelectricity, polymer piezoelectricity should originate from the polar crystalline phase. Surprisingly, the crystal contribution to the piezoelectric strain coefficient d31 is determined to be less than 10%, primarily owing to the difficulty in changing the molecular bond lengths and bond angles. Instead, >85% contribution is from Poisson's ratio, which is closely related to the oriented amorphous fraction (OAF) in uniaxially stretched films of semicrystalline ferroelectric (FE) polymers. In this perspective, the semicrystalline structure–piezoelectric property relationship is revealed using PVDF‐based FE polymers as a model system. In melt‐processed FE polymers, the OAF is often present and links the crystalline lamellae to the isotropic amorphous fraction. Molecular dynamics simulations demonstrate that the electrostrictive conformation transformation of the OAF chains induces a polarization change upon the application of either a stress (the direct piezoelectric effect) or an electric field (the converse piezoelectric effect). Meanwhile, relaxor‐like secondary crystals in OAF (SCOAF), which are favored to grow in the extended‐chain crystal (ECC) structure, can further enhance the piezoelectricity. However, the ECC structure is difficult to achieve in PVDF homopolymers without high‐pressure crystallization. We have discovered that high‐power ultrasonication can effectively induce SCOAF in PVDF homopolymers to improve its piezoelectric performance. Finally, we envision that the electrostrictive OAF mechanism should also be applicable for other FE polymers such as odd‐numbered nylons and piezoelectric biopolymers.
Modulating Ionic Linkages in the Heterocyclic Sulfated Polysaccharide Carrageenan for Enhanced Selectivity Against Amelanotic Melanoma Cells
Authors: Bhatt Akanksha , Kailkhura Shashank , Shukla Aman , Kumar Sachin , Purohit Priyank , Abdellattif Magda H.
Published: May 2024

The present research is the use of Heterocyclic sulfated polysaccharides, exemplified by carrageenan, with the high selective anti‐cancer against melanoma cancer. This study focuses on optimizing the ionic linkage of carrageenan to enhance its selectivity and activity against skin cancer cells with the help of cell line assays and in‐silico studies. The cytotoxicity and selectivity of the optimized derivatives were assessed in‐vitro against skin cancer cells and normal skin cells. The barium‐linked carrageenan demonstrated significantly increased selectivity against skin cancer cells with a selectivity index of 45, however, the reference drug was found with a selectivity index of 23. The selectivity of the compound 3 (Ba ion linked) was analysed through the ion dissociation energy and found that the more energy is require to dissoxiate in the ion, which signifiacnlty absorbs inside the cell because of non‐ionic form. The selectivity sequence of K+<Ca2+<Ba2+ as a targeted anti‐cancer agent. The present research unfold the importance of ion linkage of chromophore, to get the more active and selective compounds, which will be a path to get the ion activity relationship of various drugs without interfering the chromophore. The findings suggest a promising avenue for the development of targeted therapies with the change of ions, emphasizing the potential of heterocyclic sulfated polysaccharides in the field of cancer treatment with enhanced tuning of selectivity. The further scope is the gel formation of the Ba2+ carrageenan which will be the first API (Active Pharmaceuitical Ingredients) based formulation for skin cancer.
G‐Quadruplex‐Programmed Versatile Nanorobot Combined with Chemotherapy and Gene Therapy for Synergistic Targeted Therapy
Authors: Wang Qiwei , Du Yi , Zheng Jiao , Shi Lili , Li Tao
Published: May 2024

Developing synergistic targeted therapeutics to improve treatment efficacy while reducing side effects has proven promising for anticancer therapies, but how to conveniently modulate multidrug cooperation remains a challenge. Here, a novel synergistic strategy using a G‐quadruplex‐programmed versatile nanorobot (G4VN) containing two subunits of DNAzyme (DzG4) and ligand‐drug conjugates (LDCs) is proposed to precisely target tumors and then execute both gene silencing and chemotherapy. As the core module of this nanorobot, a well‐designed G4 responding to a high level of K+ in tumor microenvironment smartly kills three birds with one stone, which makes two TfR aptamers proximate to improve their efficiency of targeting tumor cells, and in situ activates a split 10–23 DNAzyme to downregulate target mRNA expression, meanwhile promotes the cell uptake of a GSH‐responsive LDCs to enhance drug efficacy. Such a design enables a potently synergistic anticancer therapy with low side effects in vivo, showing great promise for broad applications in precision disease treatment.
Regulation of Peptide Liquid–Liquid Phase Separation by Aromatic Amino Acid Composition
Authors: Netzer Amit , Baruch Leshem Avigail , Veretnik Shirel , Edelstein Ilan , Lampel Ayala
Published: May 2024

Membraneless organelles are cellular biomolecular condensates that are formed by liquid–liquid phase separation (LLPS) of proteins and nucleic acids. LLPS is driven by multiple weak attractive forces, including intermolecular interactions mediated by aromatic amino acids. Considering the contribution of π‐electron bearing side chains to protein‐RNA LLPS, systematically study sought to how the composition of aromatic amino acids affects the formation of heterotypic condensates and their physical properties. For this, a library of minimalistic peptide building blocks is designed containing varying number and compositions of aromatic amino acids. It is shown that the number of aromatics in the peptide sequence affect LLPS propensity, material properties and (bio)chemical stability of peptide/RNA heterotypic condensates. The findings shed light on the contribution of aromatics’ composition to the formation of heterotypic condensates. These insights can be applied for regulation of condensate material properties and improvement of their (bio)chemical stability, for various biomedical and biotechnological applications.
Chemical analysis and antibacterial susceptibility of some brands of amoxicillin suspension marketed in Sagamu, Ogun, Nigeria
Authors: Oresanya Ayooluwa Omobolanle , Ayodele Adekunle Olatunde , Awotuya Oluwafemi Iyanu , Fagbohun Babasola Ayodele , Olufolabo Olabanjo Katherine , Daodu Olabanji John , Olaitan James Olatunde , Kasim Lateef Saka
Published: May 2024

Poor quality medicines present a serious public health concern and have a significant impact on national clinical and economic burden. This study was carried out for comparative quality assessment of different brands of amoxicillin suspension in Sagamu community in Nigeria to determine their suitability for the therapeutic purpose. Ten brands of 125 mg/5 mL amoxicillin suspension, marketed in Sagamu community pharmacies were procured and subjected to chemical analysis using the high‐performance liquid chromatography method according to the official procedures in United State Pharmacopoeia (USP) and the microbiological analysis on different clinical isolates which include Pseudomonas aeruginosa, Escherichia coli, Streptococcus pyogene, and Staphylococcus aureus using agar disc diffusion antimicrobial susceptibility testing. The results of the high‐performance liquid chromatography revealed the percentage content of the brands A, B, C, D, E, F, G, H, I, and J to be 97.39%, 57.078%, 91.565%, 98.137%, 61.694%, 103.337%, 91.454%, 106.683%, 75.109%, and 96.895% w/v, respectively. The result of the high‐performance liquid chromatography reveals the brands (A, C, D, F, G, H, and J) had a percentage within the required range and were deemed unsuitable for therapeutic use. In the microbiological analysis, all the brands passed the antibacterial susceptibility testing except for brand (B, E, and I) which were not susceptible to S. aureus due to their zone of inhibition being less than 15 mm. Overall, this study emphasizes the importance of quality assurance in the pharmaceutical industry to ensure that only high‐quality drugs are made available to the population for optimal therapeutic benefit.
Water quality evaluation based on water quality index and multiple linear regression: A research on Hanyuan Lake in southern Sichuan Province, China
Authors: Su Kai , Peng Zhongshan , Zhu Dan , Liu Ruiqian , Wang Qin , Cao Rong , He Jun
Published: May 2024

This study aims to understand the changes in the water quality of Hanyuan Lake and to show these changes over time. In this study, monthly sampling was conducted at three sampling sites in Hanyuan Lake, and water samples were measured for water quality indicators in the laboratory according to the methods specified in the Environmental Quality Standards for Surface Water (GB3838‐2002). Based on the monitoring data from January to December 2019, the WQI comprehensive evaluation method was used to conduct multiple linear stepwise regression analysis, extract key indicators, and establish the WQImin model. The results show that according to the WQI comprehensive evaluation method, the WQI values of Hanyuan Lake are all above 90, and the grade is excellent. The overall water quality of Hanyuan Lake is excellent, and most of the water quality indexes reach the Class I standard in the Environmental Quality Standards for Surface Water (GB3838‐2002). WQImin1 (R2 = 0.86, p < 0.001, PE = 4.28) as the best WQImin model. In this study, a model with fewer parameters was established by multiple linear regression method, which is conducive to better monitoring of water quality at monitoring stations while saving costs.

Practitioner Points

According to the WQI comprehensive evaluation method, the WQI values of Hanyuan Lake are all above 90, the rating is excellent.

From January 2019 to September 2020, the monthly change trend of each section is roughly the same, showing a trend of first decreasing, then rising, then decreasing, and finally rising and flattening.

The WQImin model was developed to completely describe the change in the water body.
Replicating Current Procedural Terminology code assignment of rhinology operative notes using machine learning
Authors: Cheng Christopher P. , Sicard Ryan , Vujovic Dragan , Vasan Vikram , Choi Chris , Lerner David K. , Iloreta Alfred‐Marc
Published: May 2024

Objectives

Documentation and billing are important and time‐consuming parts of an otolaryngologist's work. Given advancements in machine learning (ML), we evaluated the ability of ML algorithms to use operative notes to classify rhinology procedures by Current Procedural Terminology (CPT®) code. We aimed to assess the potential for ML to replicate rhinologists' completion of their administrative tasks.

Study Design

Retrospective cohort study.

Setting

Urban tertiary hospital.

Methods

A total of 594 operative notes from rhinological procedures across six CPT codes performed from 3/2017 to 4/2022 were collected from 22 otolaryngologists. Text was preprocessed and then vectorized using CountVectorizer (CV), term frequency‐inverse document frequency, and Word2Vec. The Decision Tree, Support Vector Machine, Logistic Regression and Naïve Bayes (NB) algorithms were used to train and test models on operative notes. Model‐classified CPT codes were compared to codes assigned by operating surgeons. Model performance was evaluated by area under the receiver operating characteristic curve (ROC‐AUC), precision, recall, and F1‐score.

Results

Performance varied across vectorizers and ML algorithms. Across all performance metrics, CV and NB was most overall the best combination of vectorizer and ML algorithm across CPT codes and produced the single best AUC, 0.984.

Conclusions

In otolaryngology applications, the performance of basic ML algorithms varies depending on the context in which they are used. All algorithms demonstrated their ability to classify CPT codes well as well as the potential for using ML to replicate rhinologists' completion of their administrative tasks.
Technical details of robotic pancreatojejunostomy using a modified Blumgart anastomosis: Thread manipulation using gauze and an assisted port
Authors: Uchida Yuichiro , Takahara Takeshi , Mizumoto Takuya , Nishimura Akihiro , Mii Satoshi , Iwama Hideaki , Kojima Masayuki , Kato Yutaro , Uyama Ichiro , Suda Koichi
Published: May 2024

Backgrounds

Pancreatojejunostomy is a technically demanding procedure during robotic pancreaticoduodenectomy (RPD). Modified Blumgart anastomosis (mBA) is a common method for the pancreatojejunostomy; however, the technical details for robotic mBA are not well established. During RPD, we performed a mBA for the pancreatojejunostomy using thread manipulation with gauze and an additional assist port.

Methods

Patients who underwent robotic pancreatoduodenectomy at Fujita Health University from November 2009 to May 2023 were retrospectively investigated, and technical details for the robotic‐modified Blumgart anastomosis were demonstrated.

Results

Among 78 patients who underwent RPD during the study period, 33 underwent robotic mBA. Postoperative pancreatic fistula (POPF) occurred in six patients (18%). None of the patients suffered POPF Grade C according to the international study group of pancreatic surgery definition. The anastomotic time for mBA was 80 min (54–125 min).

Conclusion

Robotic mBA resulted in reasonable outcomes. We propose that mBA could be used as one of the standard methods for robotic pancreatojejunosotomy.
Higher-derivative corrections to flavoured BPS black hole thermodynamics and holography
Authors: Cassani Davide , Ruipérez Alejandro , Turetta Enrico
Published: May 2024

Abstract

A Cardy-like regime of the four-dimensional superconformal index has been shown to be governed by ’t Hooft anomalies and to single out a large-N saddle carrying the Bekenstein-Hawking entropy of dual supersymmetric black holes in AdS5. For the universal index where no flavour fugacities are turned on, this correspondence has been improved by matching the first subleading corrections to the saddle-point action with the four-derivative corrections to the black hole action in minimal gauged supergravity, as well as the respective corrected entropies. Here, we extend this match by including flavour symmetries. We consider five-dimensional gauged supergravity with vector multiplet and four-derivative couplings, and provide an effective theory reproducing the ’t Hooft anomalies of the R- and flavour symmetries of generic holographic superconformal field theories at next-to-leading order in the large-N expansion. Then we focus on a specific model dual to ℂ3/ℤν quiver gauge theories, where the ’t Hooft anomaly coefficients receive simple but sufficiently generic corrections. In this model, we evaluate the four-derivative corrections to the on-shell action of the supersymmetric multi-charge black hole, showing agreement with the flavoured Cardy-like formula from the index. We give a prediction for the corrected entropy of the supersymmetric black hole and discuss the general validity of our results. Taking the limit of infinite AdS5 radius, we also obtain four-derivative corrections to the action and entropy of supersymmetric asymptotically flat black holes.
A neutrino floor for the Migdal effect
Authors: Herrera Gonzalo
Published: May 2024

Abstract

Neutrino-nucleus scatterings in the detector could induce electron ionization signatures due to the Migdal effect. We derive prospects for a future detection of the Migdal effect via coherent elastic solar neutrino-nucleus scatterings in liquid xenon detectors, and discuss the irreducible background that it constitutes for the Migdal effect caused by light dark matter-nucleus scatterings. Furthermore, we explore the ionization signal induced by some neutrino electromagnetic and non-standard interactions on nuclei. In certain scenarios, we find a distinct peak on the ionization spectrum of xenon around 0.1 keV, in clear contrast to the Standard Model expectation.
A bone remodeling approach encoding the effect of damage and a diffusive bio-mechanical stimulus
Authors: Addessi Daniela , D’Annibale Francesco , Placidi Luca , Giorgio Ivan
Published: May 2024

The paper focuses on the effect of damage on the bone remodeling process. This is a crucial, although complex, aspect. A one-dimensional continuous deformable body is employed to model living bone tissue. The model incorporates the bone functional adaptation through an evolution law for an effective elastic modulus driven by mechanical feedback via a mechano-transduction diffusive signal. This type of information transduction, i.e., diffusion, is essential for the model to take into account remodeling in the case of minor injury or pathology-affected regions where there is no signal production. In addition, the model is able to also take into account potential tissue damage that may evolve over time according to a suitable evolution law. To illustrate the capability of the model to describe the mentioned complex coupled phenomena, numerical tests have been performed encompassing high external loads causing the onset of damage and cyclic loading for healing. The numerical simulations carried out via finite-element analyses yield insights into the mechanisms of bone remodeling, with the final goal of aiding clinical decisions and implant designs for bone health and repair. Overall, a key aspect of the paper is to highlight the feasibility of modeling the evolution in bone elasticity arising from the combined effect of damage and remodeling.
Existence and nonexistence of solutions for the mean curvature equation with weights
Authors: Filippucci Roberta , Zheng Yadong
Published: May 2024

In this paper we study existence and nonexistence of positive radial solutions of a Dirichlet problem for the prescribed mean curvature operator with weights in a ball with a suitable radius. Because of the presence of different weights, possibly singular or degenerate, the problem under consideration appears rather delicate, it requires an accurate qualitative analysis of the solutions, as well as the use of Liouville type results based on an appropriate Pohozaev type identity. In addition, sufficient conditions for global solutions to be oscillatory are given.
Simultaneous quantification of terpenes and cannabinoids by reversed-phase LC-APCI-MS/MS in Cannabis sativa L. samples combined with a subsequent chemometric analysis
Authors: Raeber Justine , Poetzsch Michael , Schmidli Anina , Favrod Sina , Steuer Christian
Published: May 2024

Cannabis sativa L. has been the most discussed medicinal plant in recent years. In particular, the dynamic shift from a formerly illicit and tightly controlled substance to a plant recognized for both medicinal and recreational purposes has brought C. sativa into the global spotlight. Due to the ongoing international legalization processes, fast and convenient analytical methods for the quality control of C. sativa flowers for medicinal and recreational purposes are of tremendous interest. In this study, we report the development and validation of a liquid chromatography-tandem mass spectrometry (LC–MS/MS)-based method applying atmospheric pressure chemical ionization (APCI) to fully quantify 16 terpenes and 7 cannabinoids including their acidic forms by a single chromatographic method. The method presented here is unique and simple, as it eliminates the need for derivatization reactions and includes the unconventional analysis of volatile compounds by liquid chromatography. Samples were prepared by a simple and fast ethanolic extraction. Separation was accomplished within 25 min on a reversed-phase C18 column. Method validation was conducted according to international guidelines regarding selectivity, accuracy, precision, robustness, and linearity. Detection was done in multiple reaction monitoring, which allowed the simultaneous quantification of co-eluting analytes applying two selective mass transitions. In addition, due to reproducible in-source decarboxylation, the acidic forms of cannabinoids were reliably quantified using mass transitions of the neutral forms. The accuracy given as the bias was below 15% for all analytes. Matrix effects for cannabinoids were studied by spiking Humulus lupulus extracts with the analytes at varying concentrations. APCI did not show susceptibility toward ion suppression or enhancement. In addition, the recovery effect after spiking was between 80 and 120% for terpenes. Further, 55 authentic C. sativa extracts were fully quantified, and the obtained results for the terpene profiles were compared to state-of-the-art gas chromatography coupled to flame ionization detection. Comparable results were achieved, emphasizing the method’s applicability for cannabinoids and terpenes. Further, acquired metabolite patterns for C. sativa samples were studied, identifying a relationship between cannabinoid and terpene patterns, as well as the abundance of myrcene in CBD-dominant C. sativa strains.

Graphical Abstract
The Causal Relationship between PCSK9 Inhibitors and Osteoporosis Based on Drug-Targeted Mendelian Combined Mediation Analysis
Authors: Zhang Naidan , Ji Chaixia , Liu Li , Ye Ermei , Yuan Chengliang
Published: May 2024

PCSK9 inhibitors have been shown to lower serum low density lipoprotein cholesterol (LDL-C) levels and are considered integral in the treatment of cardiovascular diseases. However, the potential association between PCSK9 inhibitors and osteoporosis is unclear now. In this study, drug-targeted mendelian randomization (MR) was utilized in conjunction with mediation analysis including bone mineral density (BMD), total 25-hydroxyvitamin D (T25(OH)D) levels and calcium supplementation to investigate the causal relationship between PCSK9 inhibitors and osteoporosis. The LDL-C level was chosen as the exposure variable in a sample size of 173,082 individuals. We conducted a MR analysis on the relationship between PCSK9 inhibitors and osteoporosis, elucidating the mediators involved. Utilizing the inverse variance weighted (IVW) method, we found the risk of osteoporosis was reduced by 0.6% in those who used PCSK9 inhibitors compared with non-users (OR: 0.994, 95%CI: 0.991–0.998, P < 0.001). In people aged 30–45 years, the risk of low BMD was 1.176 times higher among PCSK9 inhibitor users compared to non-users (OR: 1.176, 95%CI: 1.017–1.336, P = 0.045). Conversely, people aged 45–60 years who used PCSK9 inhibitors had a 14.9% lower risk of low BMD compared to non-users (OR: 0.851, 95%CI: 0.732–0.968, P = 0.007). Mediation analysis revealed that 43.33% of the impact of PCSK9 inhibitors on osteoporosis was mediated through BMD levels, with the remaining 56.67% being a direct effect. Effects of PCSK9 inhibitors on BMD levels varied in different ages. In addition, the risk of high serum T25(OH)D levels were 1.091 times among PCSK9 inhibitor users compared to non-users (OR: 1.091, 95%CI: 1.065–1.112, P < 0.001), providing valuable insights for clinicians.
Dissecting the role of soybean rhizosphere-enriched bacterial taxa in modulating nitrogen-cycling functions
Authors: Wang Tianshu , Gao Miao , Shao Weiwei , Wang Li , Yang Chunyan , Wang Xing , Yao Shuihong , Zhang Bin
Published: May 2024

Crop roots selectively recruit certain microbial taxa that are essential for supporting their growth. Within the recruited microbes, some taxa are consistently enriched in the rhizosphere across various locations and crop genotypes, while others are unique to specific planting sites or genotypes. Whether these differentially enriched taxa are different in community composition and how they interact with nutrient cycling need further investigation. Here, we sampled bulk soil and the rhizosphere soil of five soybean varieties grown in Shijiazhuang and Xuzhou, categorized the rhizosphere-enriched microbes into shared, site-specific, and variety-specific taxa, and analyzed their correlation with the diazotrophic communities and microbial genes involved in nitrogen (N) cycling. The shared taxa were dominated by Actinobacteria and Thaumarchaeota, the site-specific taxa were dominated by Actinobacteria in Shijiazhuang and by Nitrospirae in Xuzhou, while the variety-specific taxa were more evenly distributed in several phyla and contained many rare operational taxonomic units (OTUs). The rhizosphere-enriched taxa correlated with most diazotroph orders negatively but with eight orders including Rhizobiales positively. Each group within the shared, site-specific, and variety-specific taxa negatively correlated with bacterial amoA and narG in Shijiazhuang and positively correlated with archaeal amoA in Xuzhou. These results revealed that the shared, site-specific, and variety-specific taxa are distinct in community compositions but similar in associations with rhizosphere N-cycling functions. They exhibited potential in regulating the soybean roots’ selection for high-efficiency diazotrophs and the ammonia-oxidizing and denitrification processes. This study provides new insights into soybean rhizosphere-enriched microbes and their association with N cycling.

Key points

• Soybean rhizosphere affected diazotroph community and enriched nifH, amoA, and nosZ.

• Shared and site- and variety-specific taxa were dominated by different phyla.

• Rhizosphere-enriched taxa were similarly associated with N-cycle functions.
Peroperative Cooling in Rhinoplasty: Does it Differ?
Authors: Turhal Goksel , Berber Veysel , Isler Efe , Gode Sercan
Published: May 2024

The main causes of ecchymosis and edema are osteotomy (bone manipulation), dissection of subcutaneous tissue, and skin manipulation in the rhinoplasty procedure. Eyelid edema following surgery can potentially affect visual acuity, particularly during the initial twenty-four hours after the procedure. These may also delay the patient’s return to their normal social life therefore hampering their quality of life. Various surgical and medical methods have been reported to address these issues. This study aimed to compare the effects of using cold saline (0–4 °C) versus room temperature saline (20–25 °C) irrigation throughout the surgery on postoperative edema, ecchymosis, and pain. Fifty patients who underwent open-approach primary rhinoplasty between August 2022 and August 2023 at a tertiary academic center were included. Fifty patients were randomly divided into two groups depending on using cold saline (0–4 °C) (group 1) or room temperature saline (20–25 °C) (group 2) during surgical site irrigation. Patients were assessed for pain, edema, and bruising using a VAS (Visual Analog Scale) on the second and seventh postoperative days. Visual analog score (VAS) was used for subjective outcome analyses. Each patient scored the severity of their periorbital ecchymosis on day two and seven. Periorbital ecchymosis was also evaluated on the second and seventh postoperative days using the SPREE (Surgeon Periorbital Rating of Edema and Ecchymosis) scale. On the second postoperative day, the VAS pain score in group 1, where cold water was used, was found to be statistically and significantly different from the control group (group 2) (p < 0.05). However, there was no statistically significant difference between both groups when comparing the VAS pain scores on the seventh postoperative day. Regarding the VAS ecchymosis score on the seventh postoperative day, there was a statistically significant difference favoring group 1 (p < 0.05). The SPREE scale data also indicated that group 1 had significantly lower scores on the seventh day (p < 0.05). While the SPREE scores on the second day were lower in group 1 than in group 2, this difference did not reach statistical significance (p = 0.061). The findings from our study show that cold saline irrigation may contribute to intraoperative hemostasis by inducing local vasoconstriction. We observed that intraoperative bleeding decreased with the use of cold saline. This approach has the potential to improve patient satisfaction and overall quality of life by reducing postoperative ecchymosis without significantly increasing the cost of the surgical procedure.

Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Comparison of Resorption in Autogenous Dorsal Onlay Cartilage Grafts: An Experimental Study
Authors: Öner Fatih , Kozan Günay
Published: May 2024

Objectives

The present study was designed to compare the graft resorption characteristics of autogenous cartilage from the septum, auricle, and costal in the superficial muscular aponeurotic system of the nasal dorsum of the rabbit model.

Methods

Equal-sized perichondrium-free septal, auricular, and costal cartilage grafts were collected from fifteen New Zealand white rabbits. Cartilage grafts were taken at the scale of two grafts from each animal’s ear, two from its costal part, and one from its septum. Costal cartilage grafts that were shaped with a micro-motor device and monopolar electrocautery, elastic cartilage grafts that were shaped with a micro-motor device and monopolar electrocautery, and septal cartilage grafts that were shaped with a scalpel were all implanted into the dorsum of rabbit’s noses to create five groups. All autogenous cartilage tissues were removed 3 months later. Cartilages were evaluated for histological features, graft mass, and chondrocyte density resorption.

Results

The elastic cartilage group, where electrocautery was used to shape the cartilage, had a higher resorption score than the other groups. The costal cartilage graft shaped with a micro-motor was also observed to have the best cartilage regeneration score.

Conclusion

We observed that the resorption of costal cartilage was lower than that of ear and septum cartilage. It was determined that micro-motor application for the shaping process caused less resorption and stimulated more regeneration than cautery application.

Level of Evidence III

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Soil chemical properties associated with penguin carrion in Barton Peninsula, King George Island, Antarctica
Authors: Zaini Nur Adilla , Ismail Siti Sofo , Low Van Lun , Mahmud Mohd Hafizi , Houssaini Jamal , Lee Won Young , Heo Chong Chin
Published: May 2024

Carrion decomposition has a significant impact on soil chemical profiles. However, soil nutrient research associated with animal carcasses in Antarctica has been relatively scarce, and the effect of penguin carrion decomposition on soil chemical composition is largely unknown. We aimed to determine Antarctica’s soil chemistry profiles associated with penguin carrion. Soil samples were collected from a penguin rookery near King Sejong Station, Barton Peninsula, King George Island, Antarctica. Dry combustion methods were used to identify soil nitrogen and sulfur, while ammonia, nitrate, and phosphate were determined colorimetrically using a spectrophotometer. In addition, total carbon, pH, electrical conductivity, soil moisture, and soil porosity were also determined. Overall, soil chemical properties were not significantly different between the stages of decomposition and the sampling locations. These findings suggest that nutrients from penguin carrion disperse and leach in limited quantities into the soil, probably due to the active scavenging activities by vertebrate scavengers and the slower decomposition rate resulting from cold temperatures in the Antarctic region.