bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenomedullin peptides and precursor levels in relation to haemodynamics and prognosis after heart transplantation
Authors: Ahmed Abdulla , Kania Kriss , Abdul Rahim Hebba , Ahmed Salaheldin , Rådegran Göran
Published: May 2023

Aims

Heart failure (HF) is a frequent condition in the elderly, further complicated by associated pulmonary hypertension (PH), with impact on morbidity and mortality. Plasma proteins associated with cardiovascular disease, related to inflammation, neurohormonal changes, and myocyte stress, pathways recognized in the pathophysiology of HF, may provide information on disease severity and prognosis. We aimed to investigate such cardiovascular proteins and their relationship to haemodynamics before and 1 year after heart transplantation (HT), as well as their prognostic value in advanced HF with PH.

Methods and results

In 20 healthy controls and 67 patients with HF and PH, before and 1 year after HT, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and 18 cardiovascular proteins were analysed with proximity extension assay. Right heart catheterization was used to measure the haemodynamics of the HF patients pre‐operatively and at 1 year follow‐up after HT. Prognosis was estimated using Kaplan–Meier and Cox regression analyses. Out of 18 plasma proteins, 11 proteins including adrenomedullin peptides and precursor levels (ADM) and protein suppression of tumourigenicity 2 receptor were elevated before HT compared with healthy controls and had decreased 1 year after HT. The decrease in plasma levels 1 year after HT was towards the healthy controls' levels. The decrease in ADM levels before vs. after HT correlated with decreased mean right atrial pressure (rs = 0.61; P = 0.0077), decreased NT‐proBNP (rs = 0.75; P = 0.00025), and decreased stroke volume index (rs = −0.52; P = 0.022). High levels of pre‐operative plasma ADM were associated with worse event‐free survival (HT or death), as well as survival compared with low ADM levels (log‐rank P value = 0.023 and 0.0225, respectively). Univariable Cox regression analysis demonstrated that ADM levels were associated with survival, hazard ratio (HR) 1.007 (95% confidence interval (CI): 1.00–1.015, P = 0.049), and the association remained after adjusting for NT‐proBNP, HR 1.01 (95% CI: 1.00–1.021, P = 0.041).

Conclusions

Elevated plasma levels of ADM may be a marker of pressure/volume overload in HF patients with PH, as well as long‐term prognosis after HT. In line with previous studies, our findings additionally confirm that ADM may be a marker of venous congestion in HF. Further studies are encouraged to establish a deeper understanding of the properties of ADM and its relationship with HF and PH, in order to potentially facilitate clinical management of HF and associated PH.
How did the female fetus speak? Abortion, sex selection, and national futures in India
Authors: Saha Roy Sayantan
Published: May 2023

The debate around abortion is often constituted in terms of a tension between fetal personhood on the one hand and the right to bodily autonomy on the other. The supposed personhood of the fetus is widely invoked to restrict the right to abortion. In India however, one sees a paradoxical situation. Not only is there wide legal access to abortion, but this also exists simultaneously with an active legal imperative to protect the female fetus. How did the Indian state allow access to abortion while protecting a unique fetus? This paper argues that the question of reproduction and abortion in India is intimately tied to imaginations of national futures and risks and reproductive bodies have been entangled in those futures. The discourse around the legalization of abortion and the criminalization of sex‐selection offered differing but stark visions of national endangerment which played a critical role in authorizing different state actions targeting reproductive bodies while sustaining this paradox. This paper expands the anthropological understanding of the different grounds of abortion debates globally.
Acrylamide‐induced autophagy‐lysosomal pathway dysfunction contributing to neurotoxicity through targeting transcription factor EB
Authors: Yang Liuqing , Dong Li , Zhang Lujia , Li Daotong , Luo Yinghua , Chen Fang
Published: May 2023

Autophagy‐lysosomal pathway (ALP), a lysosome‐mediated self‐renewal process, is crucial for cell survival and death. Acrylamide (AA) is a neurotoxic compound produced during food thermal processing, and the mechanism underlying AA‐induced neurotoxicity remains elusive. In this study, we explored whether dysregulated ALP was involved in AA‐induced neurotoxicity and the underlying mechanism. We first evaluated the toxic effects of AA on the activation of apoptosis and NLRP3 pathway in human glioma U251 cells. We found that AA‐induced autophagy activation with the accumulation of an autophagy substrate P62, which implies the occurrence of autophagy‐lysosomal disorders. By using autophagy agonist PP242 and siRNA interfering ATG5, we demonstrated that ALP dysregulation contributed to AA‐induced apoptosis and NLRP3 inflammasome pathway activation. In addition, AA triggered ALP dysfunction by decreasing the expression of transcription factor EB (TFEB), and TFEB overexpression restored the lysosomal‐associated proteins and protected against AA‐induced apoptosis and inflammasome activation. Moreover, the autophagy agonist rapamycin restored AA‐induced ALP dysfunction by upregulating TFEB and prevented neurotoxicity. Overall, our study provides novel insights into the role of disrupted ALP in AA‐induced neurotoxicity and highlights that TFEB can be developed as a promising intervention target against AA‐induced neurotoxicity.
OpenMindat: Open and FAIR mineralogy data from the Mindat database
Authors: Ma Xiaogang , Ralph Jolyon , Zhang Jiyin , Que Xiang , Prabhu Anirudh , Morrison Shaunna M. , Hazen Robert M. , Wyborn Lesley , Lehnert Kerstin
Published: May 2023

The open data movement has brought revolutionary changes to the field of mineralogy. With a growing number of datasets made available through community efforts, researchers are now able to explore new scientific topics such as mineral ecology, mineral evolution and new classification systems. The recent results have shown that the necessary open data coupled with data science skills and expertise in mineralogy will lead to impressive new scientific discoveries. Yet, feedback from researchers also reflects the needs for better FAIRness of open data, that is, findable, accessible, interoperable and reusable for both humans and machines. In this paper, we present our recent work on building the open data service of Mindat, one of the largest mineral databases in the world. In the past years, Mindat has supported numerous scientific studies but a machine interface for data access has never been established. Through the OpenMindat project we have achieved solid progress on two activities: (1) cleanse data and improve data quality, and (2) build a data sharing platform and establish a machine interface for data query and access. We hope OpenMindat will help address the increasing data needs from researchers in mineralogy for an internationally recognized authoritative database that is fully compliant with the FAIR guiding principles and helps accelerate scientific discoveries.
Review of retrieval of aerosol optical depth to estimate particle concentration and its challenges based on spatiotemporal relationships by various spectroradiometer models
Authors: Samuel Cyril , Kumar Roshini Praveen , Gautam Sneha
Published: May 2023

This review was carried out to understand the retrieval of aerosol optical depth (AOD) datasets for estimating particle concentration and its influence on ambient air and surroundings by various models. Several studies have evaluated particle (PM10 and PM2.5) concentration profiles present in the lowest layers of the atmosphere by using AOD datasets. This study aimed at identifying consistent and precise particle estimation by various datasets retrieved by satellite‐based models for the ground‐level PM concentration. Extremities of satellite sensor data, like specific capabilities, as well as a few drawbacks are presented. Multi‐angle imaging spectroradiometer (MISR), visible infrared imaging radiometer suite (VIIRS) datasets, mixed‐effect model (MEM), and geographically weighted regression (GWR) models outperformed to estimate AOD and PM in comparison with the moderate resolution imaging spectroradiometer (MODIS) and other datasets. The improvised algorithms with higher resolution in the upcoming research would provide an even better estimation for AOD and PM.
Effect of obesity on outcomes after open laryngeal surgery including total laryngectomy: A NSQIP database analysis
Authors: Chen Tiffany , Meng Marvin L. , Hong Ellen M. , Durrant Frederick , Talmor Guy , Park Richard Chan Woo , Benson Brian
Published: May 2023

Background

The impact of obesity on outcomes after open laryngeal surgery has not been well‐described.

Methods

The NSQIP database was queried for all open laryngeal surgeries including total laryngectomies between 2005 and 2018. Outcomes of patients identified as obese or nonobese by BMI were compared.

Results

Of 1865 patients, 20.1% classified as obese. The most common operation performed was total laryngectomy with or without radical neck dissection (73.2%). Operation time and length of hospital stay were significantly less for obese patients. On multivariate analysis, obesity was associated with less bleeding transfusions occurrences (aOR, 0.395, p = 0.0052), surgical complications (aOR, 0.604, p < 0.001), and any complication (aOR, 0.730, p = 0.0019).

Conclusion

Though there may be an inverse association of obesity with complications and bleeding transfusion occurrences, as well as decreased operation time and length of hospital stay, several confounders and bias may exist; therefore, it is difficult to conclude that the obesity paradox is present.
A numerical study integrated with RSM for hydrothermal and entropy performance of porous jet impingement
Authors: Al‐damook Amer , Azzawi Itimad D. J.
Published: May 2023

The thermohydraulic and thermodynamic performance of porous jet impingement under pressure drop effect has not yet been jointly published. Thus, the novelty of this work computationally along with the response surface methodology (RSM) optimization approach considers the porous jet impingement performance linked with a pressure drop simultaneously. Also, the current study used a novel multiobjective optimum design study for various design parameters, such as porosity (ε), Darcy number (Da), and pore per inch (PPI), under numerical simulation assessment of forced laminar convection of jet impingement with full and partial metal foam. The influence of various base plate thicknesses (t = 0, 1, 2, and 3 mm), various nanofluids (Al2O3, CuO, SiO2, and ZnO), and the metal foam size percentage (W/L = 0, 0.25, 0.5, 0.75, and 1) on the improvement of the thermohydraulic and thermodynamic performance is also simulated. Results indicated that utilizing pure water and a metal foam size (W/L) of 1 along with a base plate thickness of 0 mm produced the preferable thermohydraulic and thermodynamic performance. Furthermore, according to an optimization analysis, the current study's objective for the thermohydraulic and thermodynamic performance of jet impingement can be achieved using the parameters porosity ε = 0.1, Darcy number, Da = 1, and the PPI = 15. Therefore, this investigation integrating computational fluid dynamics and RSM offers considerable innovation and useful reference for the optimum design of a porous jet impingement cooling.
A phase II trial of nifurtimox combined with topotecan and cyclophosphamide for refractory or relapsed neuroblastoma and medulloblastoma
Authors: Eslin Don , Zage Peter E. , Bergendahl Genevieve , Lewis Elizabeth , Roberts William , Kraveka Jacqueline , Mitchell Deanna , Isakoff Michael S. , Rawwas Jawhar , Wada Randal K. , Fluchel Mark , Brown Valerie I. , Ginn Kevin , Higgins Timothy , BeeravallyNagulapally Abhinav , Dykema Karl , Hanna Gina , Ferguson William , Saulnier Sholler Giselle L.
Published: May 2023

Children with relapsed/refractory (R/R) neuroblastoma (NB) and medulloblastoma (MB) have poor outcomes. We evaluated the efficacy of nifurtimox (Nfx) in a clinical trial for children with R/R NB and MB. Subjects were divided into three strata: first relapse NB, multiply R/R NB, and R/R MB. All patients received Nfx (30 mg/kg/day divided TID daily), Topotecan (0.75 mg/m2/dose, days 1‐5) and Cyclophosphamide (250 mg/m2/dose, days 1‐5) every 3 weeks. Response was assessed after every two courses using International Neuroblastoma Response Criteria and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. One hundred and twelve eligible patients were enrolled with 110 evaluable for safety and 76 evaluable for response. In stratum 1, there was a 53.9% response rate (CR + PR), and a 69.3% total benefit rate (CR + PR + SD), with an average time on therapy of 165.2 days. In stratum 2, there was a 16.3% response rate, and a 72.1% total benefit rate, and an average time on study of 158.4 days. In stratum 3, there was a 20% response rate and a 65% total benefit rate, an average time on therapy of 105.0 days. The most common side effects included bone marrow suppression and reversible neurologic complications. The combination of Nfx, topotecan and cyclophosphamide was tolerated, and the objective response rate plus SD of 69.8% in these heavily pretreated populations suggests that this combination is an effective option for patients with R/R NB and MB. Although few objective responses were observed, the high percentage of stabilization of disease and prolonged response rate in patients with multiply relapsed disease shows this combination therapy warrants further testing.
Management of large paravaginal hematomas with the Zhukovsky vaginal catheter
Authors: Barinov Sergey , Di Renzo Gian Carlo , Kadtsyna Тatyana , Nadezhina Еvgenia , Lazareva Оksana , Kochev Dmitry
Published: May 2023

Objective

To ameliorate the treatment of large paravaginal hematomas postpartum using the Zhukovsky vaginal catheter.

Methods

A retrospective, controlled study including puerperas with large paravaginal hematomas. To assess the effectiveness of the proposed treatment, a group of patients underwent traditional obstetric surgery. A second group of puerperas underwent an integrated approach: the surgical stage (pararectal incision) and the application of the Zhukovsky vaginal catheter. The effectiveness of treatment was assessed according to the following criteria: blood loss volume and hospital admission time.

Results

In total, 30 puerperas were included in the study; 15 in each treatment group. Large paravaginal hematomas were reported most often in primiparas (50.0%), in 36.7% were combined with rupture of the vagina and the cervix, and in 10.0% of cases an episiotomy was performed during delivery. In 40.0% of primiparas, the blood loss volume was more than 1000 mL, whereas in multiparous and in multiple pregnancies, blood loss did not exceed 1000 mL (r = –0.49; P = 0.022). In 25.0% of puerperas with a blood loss of up to 1000 mL there were no obstetric injuries; in the group with a blood loss of more than 1000 mL, 83.3% of patients had obstetric injuries. An integrated approach reduced the blood loss volume (r = –0.22; P = 0.29), compared with the traditional surgery, and reduced the hospital admission time from 12 (11.5; 13.5) days to 9 (7.5; 10.0) days (P < 0.001).

Conclusion

In patients with large paravaginal hematomas treated by an integrated approach we reported a decrease in bleeding, less risk of postoperative complications, and a reduction in the time of the hospital stay.
Hybrid‐Patch‐Alex: A new patch division and deep feature extraction‐based image classification model to detect COVID‐19, heart failure, and other lung conditions using medical images
Authors: Erdem Kenan , Kobat Mehmet Ali , Bilen Mehmet Nail , Balik Yunus , Alkan Sevim , Cavlak Feyzanur , Poyraz Ahmet Kursad , Barua Prabal Datta , Tuncer Ilknur , Dogan Sengul , Baygin Mehmet , Erten Mehmet , Tuncer Turker , Tan Ru‐San , Acharya U. Rajendra
Published: May 2023

COVID‐19, chronic obstructive pulmonary disease (COPD), heart failure (HF), and pneumonia can lead to acute respiratory deterioration. Prompt and accurate diagnosis is crucial for effective clinical management. Chest X‐ray (CXR) and chest computed tomography (CT) are commonly used for confirming the diagnosis, but they can be time‐consuming and biased. To address this, we developed a computationally efficient deep feature engineering model called Hybrid‐Patch‐Alex for automated COVID‐19, COPD, and HF diagnosis. We utilized one CXR dataset and two CT image datasets, including a newly collected dataset with four classes: COVID‐19, COPD, HF, and normal. Our model employed a hybrid patch division method, transfer learning with pre‐trained AlexNet, iterative neighborhood component analysis for feature selection, and three standard classifiers (k‐nearest neighbor, support vector machine, and artificial neural network) for automated classification. The model achieved high accuracy rates of 99.82%, 92.90%, and 97.02% on the respective datasets, using kNN and SVM classifiers.
Ethical dilemmas in infant mental health: Examples from child protection, home visiting, and medical contexts
Authors: Zeanah Charles H. , Korfmacher Jon , Lim Issak , Steier Alison , Zeanah Paula D.
Published: May 2023

Infant mental health is explicitly relational and strengths based as a field. Ethical dilemmas in infant mental health have received insufficient attention at the level of infant mental health professionals (IMHP) and other professionals caring for infants who must grapple with questions of when caregivers and infants have conflicting interests. We present composite cases drawn from North American and Australian contexts, using three systems in which such conflicts may commonly manifest: child protection, home visiting, and medical settings. The field of infant and early childhood mental health (IECMH) should begin to discuss such dilemmas and how best to balance the needs of caregivers and infants when they are not well aligned.
Pharmacokinetics and repeated dose 28‐day oral toxicity studies of acetaminophen nanosuspension
Authors: Karami Zahra , Bidgoli Sepideh Arbabi , Saghatchi Zanjani Mohammadreza , Arabshahi Peyman , Gazori Taraneh , Hamidi Mehrdad
Published: May 2023

Wide availability and easy accessibility of acetaminophen oral dosage forms increase the risk of intentional poisoning or unintentional organ toxicity, leading to a wide range of liver failure, nephrotoxicity, and neurotoxicity. In this study, an attempt was made to improve oral bioavailability and reduce the toxicity of acetaminophen using nanosuspension technology. The acetaminophen nanosuspensions (APAP‐NSs) were prepared by a nano‐precipitation method using polyvinyl alcohol and hydroxypropylmethylcellulose as stabilizers. The mean diameter of APAP‐NSs was 124 ± 3.8 nm. The dissolution profile of APAP‐NSs was significantly point‐to‐point higher than the coarse drug in simulated gastrointestinal fluids. The in vivo study revealed 1.6‐ and 2.8‐fold increases in the AUC0‐inf and Cmax of the drug, respectively, in APAP‐NSs‐receiving animals compared to the control group. Moreover, no deaths and no abnormalities in clinical signs, body weights, and necropsy findings were detected in the dose groups up to 100 mg/kg of the 28‐day repeated oral dose toxicity study in mice.
Men of color in the health professions: Proceedings from the 2022 ADEA Men of Color in the Health Professions Summit
Authors: Smith Carlos S. , Smith Patrick D. , Perez Herminio , Ester Todd V. , West Karen P.
Published: May 2023

The purpose of the American Dental Education Association (ADEA) Men of Color in the Health Professions Summit, held in August 2022 at ADEA's headquarters in Washington, DC, was to gather key thought leaders across a myriad of health professions and healthcare organizations and schools to cultivate intentional cross‐disciplinary efforts in championing the need to address the low number of men of color entering not only dental, but also medicine, pharmacy, and health‐related research careers. A pivotal follow‐up step from the inaugural ADEA President's Symposium on Men of Color in the Health Professions at the March 2022 ADEA Annual Session & Exhibition in Philadelphia, the summit brought together academic health professions leaders, government agencies, health professions associations, and other key stakeholders to develop an action plan to support men of color entering the health professions. Moving the needle forward and increasing opportunities for underrepresented men of color in the health professions requires all academic health professions to work together. Highlights of the Summit included a keynote presentation by David Satcher, MD, PhD, the 16th Surgeon General of the United States; workgroup consensus statement development; health career pathways program presentations; strategic forecasting regarding challenges and opportunities in developing a coalition of health professions organizations to support men of color in the health professions; and frameworks for exploring coalition building.
Equine mesenchymal stem cell derived extracellular vesicle immunopathology biomarker discovery
Authors: Reynolds David E. , Vallapureddy Phoebe , Morales Renee‐Tyler T. , Oh Daniel , Pan Menghan , Chintapula Uday , Linardi Renata L. , Gaesser Angela M. , Ortved Kyla , Ko Jina
Published: May 2023

The use of mesenchymal stem cells (MSCs) in human and veterinary clinical applications has become a subject of increasing importance due to their roles in immunomodulation and regenerative processes. MSCs are especially relevant in equine medicine because they may have the ability to treat prevalent musculoskeletal disorders, among other conditions. However, recent evidence suggests that the components secreted by MSCs, particularly extracellular vesicles (EVs), are responsible for these properties. EVs contain proteins and nucleic acids, which possess an active role in intercellular communication and can be used as therapeutics. However, because the intersection of equine veterinary medicine with EVs remains a relatively new field, there is a demand to identify biomarkers that can discern and enrich for therapeutic EVs, progressing their clinical efficacy. In this study, we identified and characterized 84 miRNAs, between three equine donors involved in immunomodulation in cell and EV subjects. We discovered distinct groups of shared miRNAs, like miR‐21‐5p and miR‐451a, that are abundant and enriched between the donors’ EVs, respectively. By mapping and comparing the MSC‐EV miRNA expression, we discovered many pathways that are involved in immunomodulation and tissue regenerative processes related to equine clinical applications. Therefore, the miRNAs highlighted in this article can be used as valuable biomarkers for screening MSC‐derived EVs for potential equine therapy.
Exploration of s new biomarker in osteosarcoma and association with clinical outcomes: TOP2A+cancer associated fibroblasts
Authors: Xu Yuanze , Chen Pingping , Liu Dongsong , Xu Qin , Meng Hao , Wang Xuesong
Published: May 2023

Background

Osteosarcoma (OS) is the leading malignant primary bone tumor in young adults and children and has a high mortality rate. Cancer‐associated fibroblasts (CAFs) are major components of the tumor microenvironment, influencing cancer progression and metastasis. However, there is no systematic study on the role of CAF in OS.

Methods

We collected six OS patients’ single‐cell RNA sequencing data from the TISCH database, which was processed using the Seurat package. We selected gene sets from the well‐known MSigDB database and resorted to the clusterprofiler package for gene set enrichment analysis (GSEA). The least absolute shrinkage and selection operator (LASSO) regression model was used for identification of the variables. Receiver operating characteristic and decision curve analyses were utilized for determining the efficacy of the monogram model.

Results

TOP2A+CAFs was recognized as the carcinogenic CAFs subset, given its intense interaction with OS malignant cells and association with the critical cancer driver pathway. We intersected the differentially expressed genes of TOP2A+CAFs with the prognostic genes selected from 88 OS samples. The acquired gene set was selected using the LASSO regression model and integrated with clinical factors to obtain a monogram model of high prognosis predicting power (area under the curve of 5 year survival at 0.883). Functional enrichment analysis revealed the detailed difference between two risk groups.

Conclusion

We identified TOP2A+CAFs as a subset of oncogenic CAFs in OS. Based on differentially expressed genes derived from TOP2A+CAFs, combined with bulk transcriptome prognostic genes, we constructed a risk model that can efficiently predict OS prognosis. Collectively, our study may provide new insights for future studies to elucidate the role of CAF in OS.
Lifetime prevalence and adherence rate of cervical cancer screening among women living with HIV: a systematic review and meta‐analysis
Authors: Gao Xiangrong , Zhang Wanting , Sun Jingyi , Adeloye Davies , Jin Huyi , Rudan Igor , Song Peige , Jin Mingjuan
Published: May 2023

Introduction

Women living with HIV (WLWH) are more likely to develop cervical cancer. Screening and available healthcare can effectively reduce its incidence and mortality rates. We aimed to summarize the lifetime prevalence and adherence rate of cervical cancer screening among WLWH across low‐ and middle‐income countries (LMICs), and high‐income countries (HICs).

Methods

We systematically searched PubMed, Web of Science and Embase for studies published between database inception and 2 September 2022, without language or geographical restrictions. Those reporting the lifetime prevalence and/or adherence rate of cervical cancer screening among WLWH were included. Pooled estimates across LMICs and HICs were obtained using DerSimonian–Laird random‐effects models. When the number of eligible studies was greater than 10, we further conducted stratified analyses by the World Health Organization (WHO) region, setting (rural vs. urban), investigation year, screening method, type of cervical cancer screening programme, age and education level.

Results

Among the 63 included articles, 26 provided data on lifetime prevalence, 24 on adherence rate and 13 on both. The pooled lifetime prevalence in LMICs was 30.2% (95% confidence interval [CI]: 21.0–41.3), compared to 92.4% in HICs (95% CI: 89.6–94.6). The pooled adherence rate was 20.1% in LMICs (95% CI: 16.4–24.3) and 59.5% in HICs (95% CI: 51.2–67.2).

Discussion

There was a large gap in cervical cancer screening among WLWH between LMICs and HICs. Further analysis found that those in LMICs had higher lifetime prevalence in subgroups with urban settings, with older age and with higher education levels; and those in HICs had higher adherence in subgroups with younger age and with higher education levels.

Conclusions

Cervical cancer screening among WLWH falls considerably short of the WHO's goal. There should be continuous efforts to further increase screening among these women, especially those residing in the rural areas of LMICs and with lower education levels.
A Pilot Study of Ratiometric Creatine CEST MRI Assessment of Rabbit Skeletal Muscle Energy Metabolism at 3 T
Authors: Zhao Jialei , Wu Gang , Wu Qiting , Gong Pengcheng , Kuang Junfeng , Zheng Hairong , Sun Phillip Zhe , Li Ye , Wu Yin
Published: May 2023

Background

pH MRI may provide useful information to evaluate metabolic disruption following ischemia. Radiofrequency amplitude‐based creatine chemical exchange saturation transfer (CrCEST) ratiometric MRI is pH‐sensitive, which could but has not been explored to examine muscle ischemia.

Purpose

To investigate skeletal muscle energy metabolism alterations with CrCEST ratiometric MRI.

Study Type

Prospective.

Animal Model

Seven adult New Zealand rabbits with ipsilateral hindlimb muscle ischemia.

Field Strength/Sequence

3 T/two MRI scans, including MRA and CEST imaging, were performed under two B1 amplitudes of 0.5 and 1.25 μT after 2 hours of hindlimb muscle ischemia and 1 hour of reperfusion recovery, respectively.

Assessment

CEST effects of two energy metabolites of creatine and phosphocreatine (PCrCEST) were resolved with the multipool Lorentzian fitting approach. The pixel‐wise CrCEST ratio was quantified by calculating the ratio of the resolved CrCEST peaks under a B1 amplitude of 1.25 μT to those under 0.5 μT in the entire muscle.

Statistical Tests

One‐way ANOVA and Pearson's correlation. P < 0.05 was considered statistically significant.

Results

MRA images confirmed the blood flow loss and restoration in the ischemic hindlimb at the ischemia and recovery phases, respectively. Ischemic muscles exhibited a significant decrease of PCr at the ischemia (under both B1 amplitudes) and recovery phases (under B1 amplitude of 0.5 μT) and significantly increased CrCEST from normal tissues at both phases (under both B1 levels). Specifically, CrCEST decreased, and PCrCEST increased with the CrCEST ratio. Significantly strong correlations were observed among the CrCEST ratio, and CrCEST and PCrCEST under both B1 levels (r > 0.80).

Data Conclusion

The CrCEST ratio altered substantially with muscle pathological states and was closely related to CEST effects of energy metabolites of Cr and PCr, suggesting that the pH‐sensitive CrCEST ratiometric MRI is feasible to evaluate muscle injuries at the metabolic level.

Evidence Level

2

Technical Efficacy Stage

1
Whether the updates of dynamical processes can improve the performance of BCC‐CSM model to reproduce the long‐range correlation of the daily temperature?
Authors: He Wenping , Zhao Shanshan , Wan Shiquan , Jiang Yundi
Published: May 2023

Many studies have shown that the climate system has the long‐range correlation (LRC) characteristics, which provide a good test bed for evaluating the performance of climate models. In this study, the LRC characteristics of the observed surface daily temperature data in China is first analysed by detrended fluctuation analysis. It is found that the daily temperature records, including daily mean temperature (Tmean), daily maximum temperature (Tmax), and daily minimum temperature (Tmin), all exhibit LRC characteristics with scaling exponents more than 0.6 in most of China. Then, the performances of two different versions for the Beijing Climate Center Climate System Model (BCC‐CSM), namely, BCC‐CSM1.1m in CMIP5 and BCC‐CMS2‐MR in CMIP6, are quantitatively evaluated by comparing the differences of the LRC characteristics between the observations and the simulations. The results indicate that BCC‐CSM2‐MR performs better than BCC‐CSM1.1(m) in western Northwest China, most of south of the middle and lower reaches of Yangtze River, North China, central Inner Mongolia for the daily Tmean and Tmax. As far as the daily Tmin is concerned, BCC‐CSM1.1(m) performs better than BCC‐CSM2‐MR in western South China and southern Xinjiang, and the performance of BCC‐CSM2‐MR in CMIP6 has not been significant improved. Compared with BCC‐CSM1.1(m), BCC‐CSM2‐MR cannot significantly improve the simulations for the LRC characteristics of the three daily temperature variables in central and eastern Qinghai‐Tibet plateau, and the areas of between lower reaches of Yellow River and Yangtze River.
Rainfall onset and cessation over Mozambique and relationship with sea surface temperature and atmospheric patterns
Authors: Manhique A. J. , Reason C. J. C. , Barimalala R.
Published: May 2023

Mozambique is highly dependent on subsistence agriculture. Thus a climatology of rainfall onset and cessation is derived together with their interannual variability and trends using gridded daily data and station data. Mean onset is found to occur from early to mid‐November over southernmost regions, mid‐ to late November over central regions and late November to early December over the northern and coastal regions while cessation is from mid to late March over southern and late March to early April over most of central and northern Mozambique. The two gridded datasets showed differences (~30 days) in rainfall onset and cessation dates over southern Mozambique with standard deviations of 20–35 days. Timing of early onset over northern and central Mozambique appears associated with both zonal and meridional moisture convergence and tropical extratropical cloud bands, while timing of late onset is associated with southeast moisture fluxes from the subtropical South Indian Ocean and uplift over the landmass. Early (late) onset appears to be linked to La Niña (El Niño), particularly over central Mozambique. Rainfall cessation over most of Mozambique tends to be early (late) during El Niño (La Niña) summers. The relationship of ENSO with onset and cessation over large areas in Mozambique may help farmers and other user groups in planning their activities for the rainy season.
Validity of the Global Leadership Initiative on Malnutrition criteria using calf circumference in the prediction of in‐hospital mortality in older surgical patients: A secondary analysis of a cohort study
Authors: Beretta Mileni V. , Rodrigues Ticiana d. C. , Steemburgo Thais
Published: May 2023

Background

Malnutrition is a prevalent condition among older patients and is associated with worse clinical outcomes. Methods such as the Subjective Global Assessment (SGA), the Mini Nutritional Assessment Long Form (MNA‐LF), and the Global Leadership Initiative on Malnutrition (GLIM) diagnose malnutrition early. This study aimed to evaluate the performance and validity of these instruments to predict the length of hospital stay (LOS) and in‐hospital mortality in older surgical patients.

Methods

This prospective cohort study was performed in hospitalized older surgical patients. In the first 48 h of admission, general data were collected, and patients were evaluated by SGA, MNA‐LF, and GLIM using calf circumference (CC) and mid‐upper arm circumference (MUAC) as phenotypic criteria for nutrition diagnoses. Accuracy tests and regression analysis adjusted for sex, type of surgery, and the Charlson Comorbidity Index adjusted for age were performed to assess the criterion validity of instruments to predict LOS and mortality.

Results

A total of 214 patients (age 75.4 ± 6.6 years, 57.3% men, and 71.1% admitted to elective surgery) were evaluated. Malnutrition was diagnosed in 39.7% (SGA), 63% (MNA‐LF), 41.6% (GLIMCC), and 32.1% (GLIMMUAC) of patients. GLIMCC had the best accuracy (AUC = 0.70; 95% CI, 0.63–0.79) and sensitivity (95.8%) to predict in‐hospital mortality. In the adjusted analysis, malnutrition, according to SGA, MNA‐LF, and GLIMCC, increased the risk of in‐hospital mortality by 3.12 (95% CI, 1.08–11.34), 4.51 (95% CI, 1.29–17.61), and 4.83 (95% CI, 1.52–15.22), respectively.

Conclusion

GLIMCC had the best performance and satisfactory criterion validity to predict in‐hospital mortality in older surgical patients.
Mineralogy of the LAR 12095 Martian shergottite as determined by micro‐Raman and micro‐X‐ray fluorescence spectroscopies
Authors: Huidobro Jennifer , Aramendia Julene , García‐Florentino Cristina , Población Iratxe , Castro Kepa , Arana Gorka , Madariaga Juan Manuel
Published: May 2023

In this work, the geochemical characterization of the olivine‐phyric Martian shergottite LAR 12095 was performed by using two complementary analytical techniques: micro‐Raman and micro‐energy dispersive X‐ray fluorescence spectroscopies. Thanks to this methodology, olivine, pyroxene, and ilmenite were detected as primary minerals from Mars. Maskelynite, hematite, anatase, chromite, merrillite, oxidized mackinawite, pyrrhotite, elemental sulfur, marcasite, jarosite, epsomite, and gypsum were classified as secondary minerals. The major novelty of this work is that alterations under anaerobic and aerobic conditions of S‐bearing minerals can be appreciated. In this sense, primary sulfides were altered to secondary sulfides, elemental sulfur and sulfates under the oxygen‐free Martian atmosphere. However, in the Earth's oxidizing atmosphere, primary sulfides are weathered to iron oxides, such as hematite. In addition, it should be highlighted that the presence of ilmenite, mackinawite, elemental sulfur, and jarosite has been reported for the first time in this meteorite.
Preparation of β‐cyclodextrin covalent organic framework‐immobilized poly(glycidyl methacrylate) nanoparticle‐coated open tubular capillary electrochromatography column for chiral separation
Authors: Huo Hongyi , Guan Jin , Huang Ziwei , Long Ke , Zhang Dongxiang , Shi Shuang , Yan Feng
Published: May 2023

A new enantioselective open‐tubular capillary electrochromatography was developed employing poly(glycidyl methacrylate) nanoparticles/β‐cyclodextrin covalent organic frameworks chemically immobilized on the inner wall of the capillary as a stationary phase. A pretreated silica‐fused capillary reacted with 3‐aminopropyl‐trimethoxysilane followed by poly(glycidyl methacrylate) nanoparticles and β‐cyclodextrin covalent organic frameworks through a ring‐opening reaction. The resulting coating layer on the capillary was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The electroosmotic flow was studied to evaluate the variation of the immobilized columns. The chiral separation performance of the fabricated capillary columns was validated by the analysis of the four racemic proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, and omeprazole. The influences of bonding concentration, bonding time, bonding temperature, buffer type and concentration, buffer pH, and applied voltage on the enantioseparation of four proton pump inhibitors were investigated. Good enantioseparation efficiencies were achieved for all enantiomers. In the optimum conditions, the enantiomers of four proton pump inhibitors were fully resolved within 10 min with high resolutions of 9.5–13.9. The column‐to‐column and inter‐ to intra‐day repeatability of the fabricated capillary columns through relative standard deviation were found better than 9.54%, exhibiting satisfactory stability and repeatability of the fabricated capillary columns.
Dispersive solid‐phase extraction of alkaloids and polyphenols using borate hypercrosslinked polymers
Authors: Liu Xiaobing , Wang Pan , Hu Kai , Li Lixin , Yang Cheng , Chen Zhihong , Zeng Huahui , Zhang Zhenqiang
Published: May 2023

In this study, a borate hyper‐crosslinked polymer was synthesized by crosslinking 1‐naphthalene boric acid and dimethoxymethane via the Friedel‐Crafts reaction. The prepared polymer exhibits excellent adsorption performance toward alkaloids and polyphenols with maximum adsorption capacities ranging from 25.07 to 39.60 mg/g. Adsorption kinetics and isotherms model results indicated the adsorption was a monolayer and chemical process. Under the optimal extraction conditions, a sensitive method was established for the simultaneous quantification of alkaloids and polyphenols in green tea and Coptis chinensis by coupling with the proposed sorbent and ultra‐high performance liquid chromatography detection. The proposed method exhibited a wide linear range of 5.0–5000.0 ng/ml with R2 ≥ 0.99, a low limit of detection (0.66–11.25 ng/ml), and satisfactory recoveries (81.2%–117.4%). This work provides a simple and convenient candidate for the sensitive determination of alkaloids and polyphenols in green tea and complex herbal products.
Mulberry Posterior Inferior Nasal Turbinate Is Associated with a Lower Pharyngeal pH Environment
Authors: Javorská Zuzana , Zeleník Karol , Lukáčová Kristína , Taimrová Renata , Vrtková Adéla , Hránková Viktória , Lubojacký Jakub , Formánek Martin , Tedla Miroslav
Published: May 2023

Objectives

Mulberry‐like changes of the posterior inferior nasal turbinate (MPINT) can lead to nasal obstruction. Extraesophageal reflux (EER) characterized by lower pH causes mucosal inflammation and therefore can contribute to sinonasal pathologies. No prior studies have objectively examined the possible association between acidic pH and MPINT formation. Therefore, this study is aimed to investigate the 24‐h pharyngeal pH value in patients with MPINT.

Study design

Prospective case–control multi‐center study.

Methods

Fifty‐five patients with chronic EER symptoms were included in the study. They filled in questionnaires aimed at reflux and sinonasal symptoms (RSI®, SNOT‐22) and underwent video endoscopy evaluating the laryngeal findings (RFS®) and the presence or absence of the MPINT. And, 24‐h oropharyngeal pH monitoring was used to detect the acidic pH environment in the pharynx.

Results

Out of the 55 analyzed patients, 38 had the MPINT (group 1), and in 17 patients, the MPINT was absent (group 2). Based on the pathological RYAN Score, in 29 (52.7%) patients, severe acidic pH drops were detected. In group 1, the acidic pH drops were diagnosed significantly more often (68.4%) compared with those in group 2 (p = 0.001). Moreover, in group 1, a significantly higher median total percentage of time spent below pH 5.5 (p = 0.005), as well as a higher median number of events lasting more than 5 min (p = 0.006), and higher median total number of events with pH drops (p = 0.017) were observed.

Conclusion

In this study, the MPINT was significantly more often present in patients with acidic pH events detected by 24‐h oropharyngeal pH monitoring. Acidic pH in the pharynx might lead to MPINT formation.

Level of Evidence

3 Laryngoscope, 134:62–68, 2024
Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies
Authors: Shen Jinze , Wang Qurui , Mao Yunan , Gao Wei , Duan Shiwei
Published: May 2023

Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted therapy of the p53 signaling pathway is still in its early stages and only a few drugs or treatments have entered clinical trials, the development of new drugs and ongoing clinical trials are expected to lead to the widespread use of p53 signaling‐targeted therapy in cancer treatment in the future. TRIAP1 is a novel p53 downstream inhibitor of apoptosis. TRIAP1 is the homolog of yeast mitochondrial intermembrane protein MDM35, which can play a tumor‐promoting role by blocking the mitochondria‐dependent apoptosis pathway. This work provides a systematic overview of recent basic research and clinical progress in the p53 signaling pathway and proposes that TRIAP1 is an important therapeutic target downstream of p53 signaling.
Multiscale Monte Carlo simulations of gold nanoparticle dose‐enhanced radiotherapy II. Cellular dose enhancement within macroscopic tumor models
Authors: Martinov Martin P. , Fletcher Elizabeth M. , Thomson Rowan M.
Published: May 2023

Background

Gold NanoParticle (GNP) dose‐enhanced radiation therapy (GNPT) requires consideration of physics across macro‐ to microscopic length scales, however, this presents computational challenges that have limited previous investigations.

Purpose

To develop and apply multiscale Monte Carlo (MC) simulations to assess variations in nucleus and cytoplasm dose enhancement factors (n,cDEFs) over tumor‐scale volumes.

Methods

The intrinsic variation of n,cDEFs (due to fluctuations in local gold concentration and cell/nucleus size variation) are estimated via MC modeling of varied cellular GNP uptake and cell/nucleus sizes. Then, the Heterogeneous MultiScale (HetMS) model is implemented in MC simulations by combining detailed models of populations of cells containing GNPs within simplified macroscopic tissue models to evaluate n,cDEFs. Simulations of tumors with spatially uniform gold concentrations (5, 10, or 20 mgAu/gtissue) and spatially varying gold concentrations eluted from a point are performed to determine n,cDEFs as a function of distance from the source for 10 to 370 keV photons. All simulations are performed for three different intracellular GNP configurations: GNPs distributed on the surface of the nucleus (perinuclear) and GNPs packed into one or four endosome(s).

Results

Intrinsic variations in n,cDEFs can be substantial, for example, if GNP uptake and cell/nucleus radii are varied by 20%, variations of up to 52% in nDEF and 25% in cDEF are observed compared to the nominal values for uniform cell/nucleus size and GNP concentration. In HetMS models of macroscopic tumors, subunity n,cDEFs (i.e., dose decreases) can occur for low energies and high gold concentrations due to attenuation of primary photons through the gold‐filled volumes, for example, n,cDEF<1 is observed 3 mm from a 20 keV source for the four endosome configuration. In HetMS simulations of tumors with spatially uniform gold concentrations, n,cDEFs decrease with depth into the tumor as photons are attenuated, with relative differences between GNP models remaining approximately constant with depth in the tumor. Similar initial n,cDEF decreases with radius are seen in the tumors with spatially varying gold concentrations, but the n,cDEFs for all of the GNP configurations converge to a single value for each energy as gold concentration reaches zero.

Conclusions

The HetMS framework has been implemented for multiscale MC simulations of GNPT to compute n,cDEFs over tumor‐scale volumes, with results demonstrating that cellular doses are highly sensitive to cell/nucleus size, GNP intracellular distribution, gold concentration, and cell position in tumor. This work demonstrates the importance of proper choice of computational model when simulating GNPT scenarios and the need to account for intrinsic variations in n,cDEFs due to variations in cell/nucleus size and gold concentration.
A multiparametric alternative to short inversion‐time inversion recovery for imaging inflammation: T2water and fat fraction measurement using chemical shift–encoded turbo spin‐echo MRI
Authors: Gollifer Ruaridh M. , Bray Timothy J. P. , Kruezi Ariona , Markus Julia , Choida Varvara , Hall‐Craggs Margaret A. , Bainbridge Alan
Published: May 2023

Purpose

Short‐inversion‐time inversion‐recovery MRI is used widely for imaging bone and soft‐tissue inflammation in rheumatic inflammatory diseases, but there is no widely available quantitative equivalent of this sequence. This limits our ability to objectively assess inflammation and distinguish it from other processes. To address this, we investigate the use of the widely available Dixon turbo spin echo (TSE Dixon) sequence as a practical approach to simultaneous water‐specific T2 (T2water) and fat fraction (FF) measurement.

Methods

We use a series of TSE Dixon acquisitions with varying effective TEs (TEeff) to quantify T2water and FF. The validity of this approach is assessed in a series of phantom and in vivo experiments, with reference values provided by Carr‐Purcell‐Meiboom‐Gill acquisitions, MRS, and phantoms. The effect of inflammation on parameter values is evaluated in patients with spondyloarthritis.

Results

The T2water estimates obtained from TSE Dixon were accurate compared with the reference values from Carr‐Purcell‐Meiboom‐Gill and spectroscopy in both fat‐free environments and in the presence of fat. FF measurements with T2water correction from TSE Dixon were accurate from 0% to 60% FF and were not confounded by T2water variations. In vivo imaging produced good quality images that were artifact free, produced plausible T2 values, separating and quantifying the effect of inflammation on T2water and FF.

Conclusion

The T2water and FF measurements based on TSE Dixon with effective TE increments are accurate over a range of T2 and FF values and could provide a widely available quantitative alternative to the short‐inversion‐time inversion‐recovery sequence for imaging inflamed tissue.