bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep learning-based protoacoustic signal denoising for proton range verification
Authors: Wang Jing , Sohn James J , Lei Yang , Nie Wei , Zhou Jun , Avery Stephen , Liu Tian , Yang Xiaofeng
Published: May 2023

Proton therapy is a type of radiation therapy that can provide better dose distribution compared to photon therapy by delivering most of the energy at the end of range, which is called the Bragg peak (BP). The protoacoustic technique was developed to determine the BP locations in vivo, but it requires a large dose delivery to the tissue to obtain a high number of signal averaging (NSA) to achieve a sufficient signal-to-noise ratio (SNR), which is not suitable for clinical use. A novel deep learning-based technique has been proposed to denoise acoustic signals and reduce BP range uncertainty with much lower doses. Three accelerometers were placed on the distal surface of a cylindrical polyethylene (PE) phantom to collect protoacoustic signals. In total, 512 raw signals were collected at each device. Device-specific stack autoencoder (SAE) denoising models were trained to denoise the noise-containing input signals, which were generated by averaging only 1, 2, 4, 8, 16, or 24 raw signals (low NSA signals), while the clean signals were obtained by averaging 192 raw signals (high NSA). Both supervised and unsupervised training strategies were employed, and the evaluation of the models was based on mean squared error (MSE), SNR, and BP range uncertainty. Overall, the supervised SAEs outperformed the unsupervised SAEs in BP range verification. For the high accuracy detector, it achieved a BP range uncertainty of 0.20 ± 3.44 mm by averaging over 8 raw signals, while for the other two low accuracy detectors, they achieved the BP uncertainty of 1.44 ± 6.45 mm and −0.23 ± 4.88 mm by averaging 16 raw signals, respectively. This deep learning-based denoising method has shown promising results in enhancing the SNR of protoacoustic measurements and improving the accuracy in BP range verification. It greatly reduces the dose and time for potential clinical applications.
An intelligence expert system for quality health monitoring of power transformers using testing attributes
Authors: Manoj Teruvai , Ranga Chilaka
Published: May 2023

Power transformers are very vital components in electrical power network. Deterioration of transformer’s insulation has significant impacts on its health condition. Hence, detailed analysis of insulation testing attributes is very important in diagnosing the transformer. It is possible with an effective decision-making system. In the present paper, a new grey relational-based fuzzy logic expert system is proposed for continuous health monitoring of power transformers. In this approach, ranking-based qualitative relational analysis is initially carried out in order to reduce large number of input attributes into three input health grades. These input grades are further integrated with a technically designed expert fuzzy rule base. Outputs of the proposed model are validated with the outputs of multi-criterion based fuzzy logic model presented in [Mharakurwa E T and Goboza R 2019 Multiparameter-based fuzzy logic health index assessment for oil-immersed power transformers Adv. Fuzzy Syst. 2019]. Testing data of 200 in-service transformers are utilised in the validation of both the models. It is observed from the comparison that similarity index of the proposed grey-fuzzy system is 92 percent. Several issues exist in regular transformer health assessment models such as the large number of rules, uncertainties, requirement of large training data, complexity issues are overcome by integrating the grey relational analysis with the fuzzy logic system. The proposed model can be easily implemented by all utilities and diagnostic experts of transformers.
Centralizing a controlled substance compliance and drug diversion prevention program within a multihospital health system
Authors: Neal Danielle , Mitchell Leah , Mieure Katherine
Published: May 2023

Purpose

Challenges with monitoring and detecting drug diversion in healthcare facilities continue to be a trending topic amid the opioid epidemic. This article aims to provide insight into the expansion of an academic medical center’s drug diversion and controlled substances compliance program. The justification and structure of a multihospital, centralized program are discussed.

Establishing dedicated controlled substances compliance and drug diversion resources has become increasingly common as awareness of the widespread healthcare impact has grown. One academic medical center recognized the value in expanding from 2 dedicated full-time equivalents (FTEs) with a scope of one facility to multiple FTEs with a scope of 5 facilities. The expansion included considering current practices at each facility, establishing the centralized team’s scope, gaining organizational support, recruiting a diverse team, and forming an effective committee structure.

Conclusion

There are multiple organizational benefits from establishing a centralized controlled substances compliance and drug diversion program, including standardization of processes, associated efficiencies, and effective risk mitigation by identifying inconsistent practices across the multifacility organization.
Standardized Photography of Female Genitalia and Anatomical Evaluations
Authors: Kang Yuanbo , Xia Zenan , Wang Sifan , Yu Nanze , Liu Zhifei , Qin Feng , Zhang Mingzi , Wang Xiaojun , Long Xiao , Zhu Lin
Published: May 2023

Background

Standardized photographic recording and anatomic evaluation are crucial to refined and comprehensive preoperative design and enhanced aesthetic effect of female genital cosmetic surgery.

Objectives

The authors aim to propose a standard photographic scheme and physical examination form for the anatomical assessment of patients undergoing female genital surgery.

Methods

The scheme containing 2 positions (standing and lithotomy positions) and 11 views (1 frontal and 2 oblique views from standing position; 6 frontal views with labia minora open and closed, pulled to the opposite side, clitoral hood pushed up, posterior fourchette stretched; 2 oblique views from lithotomy position) (2P11V) is applied to record pre- and postoperative appearance of the vulva. The evaluation form is utilized to record characteristics of different anatomical subunits during photography.

Results

Two hundred forty-five patients who underwent female genital surgery were enrolled in the research from October 2018 to October 2022. All the patients received preoperative and postoperative 2P11V photography with about 5-minutes’ shooting time. Various anatomical variations containing hypertrophy and prolapse of mons pubis, redundant types of labia minora and clitoral hood, incremental exposure of clitoral glans, hypo- to hypertrophy of labia majora, disappearance of interlabial groove, hypertrophy of posterior fourchette, and relation of subunits were accurately documented.

Conclusions

2P11V photographic scheme displays the isolated features of each organ and proportion relation among different parts of vulva. The standard photographic record and physical examination form offer detailed anatomical structure to surgeons and facilitate surgeons to carry out an accurate surgical design, which deserve to be promoted and applied.
Artificial intelligence-enabled microbiome-based diagnosis models for a broad spectrum of cancer types
Authors: Xu Wei , Wang Teng , Wang Nan , Zhang Haohong , Zha Yuguo , Ji Lei , Chu Yuwen , Ning Kang
Published: May 2023

Microbiome-based diagnosis of cancer is an increasingly important supplement for the genomics approach in cancer diagnosis, yet current models for microbiome-based diagnosis of cancer face difficulties in generality: not only diagnosis models could not be adapted from one cancer to another, but models built based on microbes from tissues could not be adapted for diagnosis based on microbes from blood. Therefore, a microbiome-based model suitable for a broad spectrum of cancer types is urgently needed. Here we have introduced DeepMicroCancer, a diagnosis model using artificial intelligence techniques for a broad spectrum of cancer types. Built based on the random forest models it has enabled superior performances on more than twenty types of cancers’ tissue samples. And by using the transfer learning techniques, improved accuracies could be obtained, especially for cancer types with only a few samples, which could satisfy the requirement in clinical scenarios. Moreover, transfer learning techniques have enabled high diagnosis accuracy that could also be achieved for blood samples. These results indicated that certain sets of microbes could, if excavated using advanced artificial techniques, reveal the intricate differences among cancers and healthy individuals. Collectively, DeepMicroCancer has provided a new venue for accurate diagnosis of cancer based on tissue and blood materials, which could potentially be used in clinics.
Zona pellucida family genes in Chinese pond turtle: identification, expression profiles, and role in the spermatozoa acrosome reaction
Authors: Dong Jinxiu , Pei Kejiao , Xu Wannan , Gong Mengmeng , Zhu Wenrui , Liu Siqi , Tang Min , Liu Jianjun , Xia Xingquan , Bu Xinjiang , Nie Liuwang
Published: May 2023

The zona pellucida (ZP) is an extracellular matrix that surrounds all vertebrate eggs, and it is involved in fertilization and species-specific recognition. Numerous in-depth studies of the ZP proteins of mammals, birds, amphibians, and fishes have been conducted, but systematic investigation of the ZP family genes and their role during fertilization in reptiles has not been reported to date. In this study, we identified six turtle ZP (Tu-ZP) gene subfamilies (Tu-ZP1, Tu-ZP2, Tu-ZP3, Tu-ZP4, Tu-ZPD, and Tu-ZPAX) based on whole genome sequence data from Mauremys reevesii. We found that Tu-ZP4 had large segmental duplication and was distributed on three chromosomes, and we also detected gene duplication in the other Tu-ZP genes. To evaluate the role of Tu-ZP proteins in sperm–egg binding, we assessed the expression pattern of these Tu-ZP proteins and their ability to induce the spermatozoa acrosome reaction in M. reevesii. In conclusion, this is the first report of the existence of gene duplication of Tu-ZP genes and that Tu-ZP2, Tu-ZP3, and Tu-ZPD can induce acrosome exocytosis of spermatogenesis in the reptile.
Chromosome-level genome assembly of Lilford’s wall lizard, Podarcis lilfordi (Günther, 1874) from the Balearic Islands (Spain)
Authors: Gomez-Garrido Jessica , Cruz Fernando , Alioto Tyler S , Feiner Nathalie , Uller Tobias , Gut Marta , Sanchez Escudero Ignacio , Tavecchia Giacomo , Rotger Andreu , Otalora Acevedo Katherin Eliana , Baldo Laura
Published: May 2023

The Mediterranean lizard Podarcis lilfordi is an emblematic species of the Balearic Islands. The extensive phenotypic diversity among extant isolated populations makes the species a great insular model system for eco-evolutionary studies, as well as a challenging target for conservation management plans. Here we report the first high-quality chromosome-level assembly and annotation of the P. lilfordi genome, along with its mitogenome, based on a mixed sequencing strategy (10X Genomics linked reads, Oxford Nanopore Technologies long reads and Hi-C scaffolding) coupled with extensive transcriptomic data (Illumina and PacBio). The genome assembly (1.5 Gb) is highly contiguous (N50 = 90 Mb) and complete, with 99% of the sequence assigned to candidate chromosomal sequences and >97% gene completeness. We annotated a total of 25,663 protein-coding genes translating into 38,615 proteins. Comparison to the genome of the related species Podarcis muralis revealed substantial similarity in genome size, annotation metrics, repeat content, and a strong collinearity, despite their evolutionary distance (~18–20 MYA). This genome expands the repertoire of available reptilian genomes and will facilitate the exploration of the molecular and evolutionary processes underlying the extraordinary phenotypic diversity of this insular species, while providing a critical resource for conservation genomics.
Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation
Authors: Althunayyan Aeshah M , Alborikan Sahar , Badiani Sveeta , Wong Kit , Uppal Rakesh , Patel Nikhil , Petersen Steffen E , Lloyd Guy , Bhattacharyya Sanjeev
Published: May 2023

Aims

Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery.

Methods and results

Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01–1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00–2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment.

Conclusion

Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.
Sleep duration and its association with adiposity markers in adolescence: a cross-sectional and longitudinal study
Authors: Martínez-Gómez Jesús , Fernández-Alvira Juan Miguel , de Cos-Gandoy Amaya , Bodega Patricia , de Miguel Mercedes , Tresserra-Rimbau Anna , Laveriano-Santos Emily P , Carral Vanesa , Carvajal Isabel , Estruch Ramón , Lamuela-Raventós Rosa María , Santos-Beneit Gloria , Fuster Valentín , Fernández-Jiménez Rodrigo
Published: May 2023

Aims

Large studies linking adolescents’ objectively measured sleep duration and adiposity markers are lacking. We characterized sleep duration and its cross-sectional and longitudinal associations with adiposity markers in adolescence.

Methods and results

Seven-day accelerometry was performed in a cohort of adolescents enrolled in the SI! Program for Secondary Schools trial in Spain at approximately ages 12 (1216 adolescents, 49.6% girls), 14 (1026 adolescents, 51.3% girls), and 16 (872 adolescents, 51.7% girls) years. Participants were classified as very short sleepers (VSS; <7 h), short sleepers (SS; 7–<8 h), or recommended-time sleepers (RTS; 8–10 h). Adjusted associations between sleep duration and adiposity markers were analysed using generalized linear and Poisson models. At ∼12 years, 33.7% of adolescents met sleep recommendations, and this percentage decreased with advancing age (22.6% at ∼14 and 18.7% at ∼16 years). Compared with RTS, overweight/obesity prevalence ratios at ∼12, 14, and 16 years among SS were 1.19 [95% confidence interval (CI): 1.09–1.30], 1.41 (95% CI: 1.34–1.48), and 0.99 (95% CI: 0.77–1.26) and among VSS were 1.30 (95% CI: 1.28–1.32), 1.93 (95% CI: 1.41–2.64), and 1.32 (95% CI: 1.26–1.37). Compared with adolescents who always met sleep recommendations, the prevalence of overweight/obesity was ∼5 times higher in those never meeting recommendations or meeting them only once. Similar trends were observed for the waist-to-height ratio (P = 0.010) and fat mass index (P = 0.024).

Conclusion

Most adolescents did not meet sleep recommendations. Shorter sleep duration was independently associated with unfavourable adiposity markers, and such adverse impact was cumulative. Health promotion programmes should emphasize the importance of good sleep habits.
Emotional demands and all-cause and diagnosis-specific long-term sickness absence: a prospective cohort study in Sweden
Authors: Framke Elisabeth , Alexanderson Kristina , Sørensen Jeppe Karl , Pedersen Jacob , Madsen Ida E H , Rugulies Reiner , Farrants Kristin
Published: May 2023

Background

High emotional demands at work require sustained emotional effort and are associated with adverse health outcomes. We tested whether individuals in occupations with high emotional demands, compared with low demands, had a higher future risk of all-cause long-term sickness absence (LTSA). We further explored whether the risk of LTSA associated with high emotional demands differed by LTSA diagnoses.

Methods

We conducted a prospective, nationwide cohort study on the association between emotional demands and LTSA (>30 days) in the workforce in Sweden (n = 3 905 685) during a 7-year follow-up. Using Cox regression, we analyzed sex-stratified risks of all-cause and diagnosis-specific LTSA due to common mental disorders (CMD), musculoskeletal disorders (MSD) and all other diagnoses. Multivariable adjusted models included age, birth country, education, living area, family situation and physical work demands.

Results

Working in emotionally demanding occupations was associated with a higher risk of all-cause LTSA in women [hazard ratio (HR) = 1.92, 95% confidence interval (CI): 1.88–1.96] and men (HR = 1.23, 95% CI: 1.21–1.25). In women, the higher risk was similar for LTSA due to CMD, MSD and all other diagnoses (HR of 1.82, 1.92 and 1.93, respectively). In men, risk of LTSA due to CMD was pronounced (HR = 2.01, 95% CI: 1.92–2.11), whereas risk of LTSA due to MSD and all other diagnoses was only slightly elevated (HR of 1.13, both outcomes).

Conclusions

Workers in occupations with high emotional demands had a higher risk of all-cause LTSA. In women, risk of all-cause and diagnosis-specific LTSA were similar. In men, the risk was more pronounced for LTSA due to CMD.
The Lure of Technocracy? Chinese Aid and Local Preferences for Development Leadership in Africa
Authors: Huang Zhenqian , Cao Xun
Published: May 2023

Should politicians, technocrats, or the free market guide the economic development of a developing country? The historical development paths of countries vary widely. Public opinion concerning development models also differs across space and over time. Using Chinese aid data from AidData and the second round Afrobarometer survey, we study how Chinese aid affects local preferences for economic leadership in sixteen African countries, 2000–2005. Our causal identification strategy is to compare the preferences of respondents who lived near an aid project site where a Chinese project had been implemented at the time of the interview (treated group) to individuals who lived close to a site where a Chinese project would be initiated shortly after the interview (control group). We find that Chinese aid increases the local population's support for economic experts to run the economy. World Bank aid, on the other hand, has no impact on local preferences for economic leadership.
The Population Attributable Fraction of Dementia From Audiometric Hearing Loss Among a Nationally Representative Sample of Community-Dwelling Older Adults
Authors: Smith Jason R , Huang Alison R , Lin Frank R , Reed Nicholas S , Deal Jennifer A
Published: May 2023

Background

The population attributable fraction (PAF) of dementia from hearing loss (HL) in the United States is ~2% when incorporating self-reported HL measures. However, self-report might underestimate clinically significant audiometric HL among older adults. Here, we quantified PAFs of dementia from audiometric HL overall and by age, sex, and race/ethnicity groups among a nationally representative sample of community-dwelling older adults in the United States.

Methods

We used cross-sectional data from Round 11 (2021) of the National Health and Aging Trends Study, a prospective cohort study representing the U.S. Medicare population aged 65+ years (N = 2 470). We estimated model-adjusted PAFs of prevalent dementia by audiometric HL (pure-tone averages: normal hearing, <26 dB HL; mild HL, 26–40 dB HL; moderate or greater HL, ≥41 dB HL).

Results

Among eligible participants (34.8% aged ≥80 years; 55.3% female; 82.4% non-Hispanic White), 37.5% had mild, and 28.8% had moderate or greater HL. Dementia prevalence overall was 10.6%, with the PAF predominately driven by moderate or greater HL (PAF = 16.9%; 95% confidence interval [CI]: 4.1–28.7%). The PAF from any degree of HL was larger but with a wider CI (PAF = 18.7%, 95% CI: −5.3% to 40.1%). There was evidence associations differed by sex but not age or race/ethnicity; moderate or greater HL exhibited stronger associations among males (PAF = 40.5%; 95% CI: 19.5% to 57.2%) than females (PAF = 3.2%; 95% CI: −12.7% to 17.9%).

Conclusions

In a nationally representative sample of community-dwelling older adults in the United States, 17% of dementia cases were attributable to moderate or greater audiometric HL, an estimate that is eightfold higher relative to studies relying on self-reported hearing measures only.
PsERF1B-PsMYB10.1-PsbHLH3 module enhances anthocyanin biosynthesis in the flesh-reddening of amber-fleshed plum (cv. Friar) fruit in response to cold storage
Authors: Xu Ranran , Wang Yubei , Wang Limin , Zhao Zhilei , Cao Jiankang , Fu Daqi , Jiang Weibo
Published: May 2023

Flesh-reddening usually occurs in the amber-fleshed plum (Prunus salicina Lindl.) fruit during cold storage but not during ambient storage direct after harvest. It is not clear how postharvest cold signal is mediated to regulate the anthocyanin biosynthesis in the forming of flesh-reddening yet. In this study, anthocyanins dramatically accumulated and ethylene produced in the ‘Friar’ plums during cold storage, in comparison with plums directly stored at ambient temperature. Expression of genes associated with anthocyanin biosynthesis, as well as transcription factors of PsMYB10.1, PsbHLH3, and PsERF1B were strongly stimulated to upregulated in the plums in the period of cold storage. Suppression of ethylene act with 1-methylcyclopropene greatly suppressed flesh-reddening and downregulated the expression of these genes. Transient overexpression and virus-induced gene silencing assays in plum flesh indicated that PsMYB10.1 encodes a positive regulator of anthocyanin accumulation. The transient overexpression of PsERF1B, coupled with PsMYB10.1 and PsbHLH3, could further prompt the anthocyanin biosynthesis in a tobacco leaf system. Results from yeast two-hybrid and luciferase complementation assays verified that PsERF1B directly interacted with PsMYB10.1. PsERF1B and PsMYB10.1 enhanced the activity of the promoter of PsUFGT individually, and the enhancement was prompted by the co-action of PsERF1B and PsMYB10.1. Overall, the stimulation of the PsERF1B-PsMYB10.1-PsbHLH3 module mediated cold signal in the transcriptomic supervision of the anthocyanin biosynthesis in the ‘Friar’ plums. The results thereby revealed the underlying mechanism of the postharvest alteration of the flesh phenotype of ‘Friar’ plums subjected to low temperature.
Patient and researcher stakeholder preferences for use of electronic health record data: a qualitative study to guide the design and development of a platform to honor patient preferences
Authors: Morse Brad , Kim Katherine K , Xu Zixuan , Matsumoto Cynthia G , Schilling Lisa M , Ohno-Machado Lucila , Mak Selene S , Keller Michelle S
Published: May 2023

Objective

This qualitative study aimed to understand patient and researcher perspectives regarding consent and data-sharing preferences for research and a patient-centered system to manage consent and data-sharing preferences.

Materials and Methods

We conducted focus groups with patient and researcher participants recruited from three academic health centers via snowball sampling. Discussions focused on perspectives on the use of electronic health record (EHR) data for research. Themes were identified through consensus coding, starting from an exploratory framework.

Results

We held two focus groups with patients (n = 12 patients) and two with researchers (n = 8 researchers). We identified two patient themes (1–2), one theme common to patients and researchers (3), and two researcher themes (4–5). Themes included (1) motivations for sharing EHR data, (2) perspectives on the importance of data-sharing transparency, (3) individual control of personal EHR data sharing, (4) how EHR data benefits research, and (5) challenges researchers face using EHR data.

Discussion

Patients expressed a tension between the benefits of their data being used in studies to benefit themselves/others and avoiding risk by limiting data access. Patients resolved this tension by acknowledging they would often share their data but wanted greater transparency on its use. Researchers expressed concern about incorporating bias into datasets if patients opted out.

Conclusions

A research consent and data-sharing platform must consider two competing goals: empowering patients to have more control over their data and maintaining the integrity of secondary data sources. Health systems and researchers should increase trust-building efforts with patients to engender trust in data access and use.
Computer-Aided Design of Eco-Friendly Imprinted Polymer Decorated Sensors Augmented by Self-Validated Ensemble Modeling Designs for the Quantitation of Drotaverine Hydrochloride in Dosage Form and Human Plasma
Authors: E. Mostafa Aziza , Eissa Maya S , Elsonbaty Ahmed , Attala Khaled , A. Abdel Salam Randa , M. Hadad Ghada , Abdelshakour Mohamed A
Published: May 2023

Background

Computationally designed molecular imprinted polymer (MIP) incorporation into electrochemical sensors has many advantages to the performance of the designed sensors. The innovative self-validated ensemble modeling (SVEM) approach is a smart machine learning-based (ML) technique that enables the design of more accurate predictive models using smaller data sets.

Objective

The novel SVEM experimental design methodology is exploited here exclusively to optimize the composition of four eco-friendly PVC membranes augmented by a computationally designed magnetic molecularly imprinted polymer to quantitatively determine drotaverine hydrochloride (DVN) in its combined dosage form and human plasma. Furthermore, the application of hybrid computational simulations such as molecular dynamics and quantum mechanical calculations (MD/QM) is a time-saving and eco-friendly provider for the tailored design of the MIP particles.

Method

Here, for the first time, the predictive power of ML is assembled with computational simulations to develop four PVC-based sensors decorated by computationally designed MIP particles using four different experimental designs known as central composite, SVEM-LASSO, SVEM-FWD, and SVEM-PFWD. The pioneering AGREE approach further assessed the greenness of the analytical methods, proving their eco-friendliness.

Results

The proposed sensors showed decent Nernstian responses toward DVN in the range of 58.60–59.09 mV/decade with a linear quantitative range of 1 × 10−7 – 1 × 10−2 M and limits of detection in the range of 9.55 × 10−8 to 7.08 × 10−8 M. Moreover, the proposed sensors showed ultimate eco-friendliness and selectivity for their target in its combined dosage form and spiked human plasma.

Conclusions

The proposed sensors were validated in accordance with International Union of Pure and Applied Chemistry (IUPAC) recommendations, proving their sensitivity and selectivity for drotaverine determination in dosage form and human plasma.

Highlights

This work presents the first ever application of both the innovative SVEM designs and MD/QM simulations in the optimization and fabrication of drotaverine-sensitive and selective MIP-decorated PVC sensors.
Green Easily Implemented Spectrophotometric Methods for Concurrent Determination of Ephedrine Hydrochloride and Naphazoline Nitrate in Nasal Preparations Containing Methylparaben
Authors: Abdelfatah Rehab M , Magdy Maimana A
Published: May 2023

Background

Spectrophotometric resolution of a mixture of several drugs is considered a cheaper, simpler, and more versatile alternative compared to costly chromatographic instruments.

Objective

The work aims to resolve the interfering spectra of ephedrine hydrochloride, naphazoline nitrate, and methylparaben in nasal preparations using smart spectrophotometric methods.

Method

In our work, derivative and dual-wavelength methods were combined to eliminate this interference, under the name of derivative dual-wavelength method. Other methods, namely successive derivative subtraction and chemometric analysis, were also able to eliminate this interference. The methods have proven their applicability as they follow the International Conference on Harmonization (ICH) requirements regarding repeatability, precision, accuracy, selectivity, and linearity. Eco-scale, GAPI, and AGREE tools were used to estimate the possible environmental effects of the methods.

Results

Acceptable results for repeatability, precision, accuracy, selectivity, and linearity were obtained. Limit of detection (LOD) values were 2.2 for ephedrine and 0.3 for naphazoline. The correlation coefficients were above 0.999. The methods were proven to be safe for application.

Conclusions

The introduced methods are cheap and easily implemented compared to chromatographic techniques. They can be used in purity-checking of raw material and estimation of concentrations in market formulations. The replacement of the published chromatographic techniques with our developed methods is useful when needing to save money, effort, and time.

Highlights

The three components of a decongestant nasal preparation were determined using cheap, green, and versatile spectrophotometric methods that keep the advantages of chromatographic techniques, including accuracy, reproducibility, and selectivity.
55 Investigating the Potential Benefits of an Immunostimulant (Mycobacterium Cell Wall Fraction) Treatment on Increased Pregnancy Success of Embryo Transfer Recipients
Authors: Vidlund Trinity , Pancini Stefania , Goncherenko Guillermo , Dias Nicholas W , Craun Hannah , Klonicke Zachary , Hinshaw Randall , Switzer Matthew , Giles Ryan , Mercadante Vitor R G
Published: May 2023

Modulating the vaginal and uterine microbiome through the use of immunostimulants has the potential to improve fertility in cattle. The object of this study was to evaluate the potential benefits of an immunostimulant, mycobacterium cell wall fraction (MCWF), to increase pregnancy success of embryo transfer (ET) recipients. The three main objectives of this study were: determining if injecting ET recipient cows with MCWF increased proportion of cows with a corpus luteum (CL) on ET day, identifying differences in CL volume and progesterone concentration at the time of ET, and determining if ET recipients that received MCWF have greater pregnancy rate. A total of 926 beef cows at eight different locations were enrolled in this study. Primiparous and multiparous cattle were enrolled in a 7-day CO-Synch + CIDR estrous synchronization protocol. During this protocol, cows received an injection of GnRH (100-μg) at CIDR (controlled internal drug release) insertion [d -9], a prostaglandin F2α injection (25 mg), and CIDR removal [d-2] followed by another injection of GnRH (100 μg; d 0) within 60-66 hours after CIDR removal. At each location at (d 0), cows were sorted based on BCS and days post-partum and randomly assigned to one of two treatments: 1) MCWF- a single intramuscular injection (5 mL) of MCWF at (d 0; Amplimune, NovaVive Inc.; n = 452) or 2) Control- a single intramuscular injection (5 mL) of saline (n = 474). Seven days after (d 7), cows were examined by ultrasonography to determine if a CL was present. Recipient cows that had a CL received ET with a frozen or fresh in vivo or in vitro produced embryo in the ipsilateral uterine horn to the CL, with embryo type and grade balanced between treatments. Blood samples were collected in one location (n = 98) for analysis of plasma concentration of progesterone on (d 7) ET day. Pregnancy diagnosis was then performed by ultrasonography between 30 and 90 days of gestation. Data were analyzed using the GLIMMIX and MIXED procedures of SAS. Cow BCS and days postpartum were similar (P > 0.10) between treatments (5.5 ± 0.6 and 103 ± 14 days, respectively). Recipient cow utilization rate was similar between treatments (P = 0.49; 81.2 ± 0.42%). At the time of ET MCWF had larger CL than Control cows (5,768.6 ± 133.7 and 5,408.0 ± 128.5 mm3, respectively, P = 0.03). and increased progesterone concentration (2.68 ± 0.17 and 2.18 ± 0.14 ng/mL, respectively, P = 0.01). However, pregnancy rate to ET was similar (P = 0.922) between treatments (60.9 and 61.3 ± 0.05% for Control and MCWF, respectively). In conclusion, treatment of ET recipient cows with MCWF increased CL volume and concentration of progesterone at the time of ET but failed to generate greater pregnancy rates.
129 Case Study: Passage Dynamics of Whole Cottonseed in Beef Cattle
Authors: Underwood Anna G , Martin Steve , Greene Wayne , Smith William B
Published: May 2023

Whole cottonseed (WCS) has long been a viable supplement in southern beef production systems, but new cultivars and ginning innovations have renewed interest in its use. Ad libitum supplementation of WCS, however, leads to increased fat intake, potentially resulting in reduced fiber digestibility. However, gestating and lactating beef cows have been observed to have adequate or optimum performance under supplementation scenarios as much as 3.6 kg∙animal-1∙day-1. It has been hypothesized that WCS may pass through the gastrointestinal tract without being digested, thereby not interfering with whole diet digestibility. Thus, our objective was to conduct an observational screening of beef cattle offered near ad libitum levels of WCS for passage dynamics. In this case study, we sampled beef cattle (approximately 1,000 head) at a farm in central Alabama offered an average of 3.6 kg WCS∙animal-1∙day-1. Cattle were divided by age and stage of production across seven pastures varying in forage base. Fresh manure samples (n = 22) were collected at random from the herd. Fecal samples were sorted by wet sieving to recover undigested seed material. Counts were conducted to determine whole or fractional seed remaining. Data were analyzed using SAS v. 9.4. Across samples, recovered WCS were approximately normally distributed (W = 0.83) with a mean of 3.3 seed per sample and a range of 2 to 76. Fractional WCS recovered were normally distributed (W = 0.92) with a mean of 31.9 parts per sample and a range of 0 to4. On average, WCS recovered accounted for 0.34 g per sample, or 5.0% of the DM recovered. While caution should be used in broad interpretation of these observational results, there is sufficient evidence to suggest that high levels of WCS supplementation may seed to decreased digestive efficiency (evidenced by undigested seed in manure). These observations serve as a basis for further investigation in designed experiments to evaluate WCS digestion and passage dynamics.
158 Evaluating Lipopolysaccharide-Induced Behavioral and Immune Response Differences in Sheep Divergently Bred for Parasite Resistance
Authors: Bentley Kelsey , Wright Donald L , Greiner Scott P , Bowdridge Scott A
Published: May 2023

Katahdin lambs with decreased post weaning worm egg count estimated breeding values (PWEC EBV) generated greater antibody in response to vaccination and survive better to weaning. Thus, lambs with decreased PWEC values may be more disease resistant and immunocompetent. To test this hypothesis, parasite-resistant St. Croix sheep, (STC, n = 10), and parasite-susceptible Suffolk sheep (SUF, n = 10) were compared with Katahdin sheep divergent in PWEC EBV (HiKAT, n = 10; LoKAT, n = 10) and challenged with lipopolysaccharide (LPS). Sheep were intravenously administered LPS at a dose of 2.5 ug/kg; blood and body temperature data were collected hourly. Behavioral observations were recorded during sampling and videos within pens were obtained 30 min after blood collection. An increase of body temperature by 1 ºC was observed in all groups. Interestingly, STC and SUF temperature peaked at 4 hours whereas LoKAT and HiKAT both peaked at 6 hours. One metric of behavior recorded from video was Sheep Grimace Score (SGS; 1 = normal; 7 = extremely abnormal). Peak SGS in all groups was 3 hours after LPS administration. Main effects of group on SGS indicated a stepwise increase with STC having the least SGS (1.25) and SUF greatest score (2.45) and both groups of Katahdin sheep intermediate (1.65 LoKAT, 2.00 HiKAT; P < 0.001). Evaluation of “return to normal” (RTN), when SGS scores average between 0 and, revealed that STC and LoKAT RTN segregated from the other groups and this occurred at 5.1 and 6.6 hours after LPS treatment, respectively. HiKAT and SUF RTN was at 9.3 and 9.6 hours, respectively. Average SGS RTN in STC and LoKAT were significantly less than HiKAT and SUF (P < 0.01), indicating segregation in behavior. Typical behaviors associated with LPS response, such as fever and ill-behaviors, can be attributed to the rapid and systemic influx of proinflammatory cytokines like tumor necrosis factor alpha (TNFα). Analysis of circulating TNFα revealed similar segregation whereas STC and LoKAT have early TNFα peak at 4 hours and then gradually decline, HiKAT and SUF peak at 9hrs and remain elevated to2hrs. The transition period between these two disparate groups is 6 hours post LPS administration. Thus, TNFα was evaluated before (-2 to 6 hours) and post (7 to 12hours) TNFα shift. With STC sheep having greater TNFα before (45.96 pg/mL, P < 0.001) and SUF sheep having greater TNFα post (47.51 pg/mL, P < 0.001) indicating that despite similar average TNFα there exists timing differences of TNFα that correspond with SGS. These differences are mirrored in the production of TNFα in LoKAT and HiKAT sheep. Taken together these data indicate that early resolvement of TNFα cytokine production within the parasite-resistant groups (STC and LoKAT) is associated with reduced duration of sick behaviors.
Screening as Governmental Technology: The Nationwide Collection of Mental Health Data on Students in South Korea
Authors: Shin Youjung
Published: May 2023

In 2012, all the students in South Korea from elementary to high school went through the government’s mental health screening. From a historical perspective, this paper examines why and how the Korean government launched the mass screening of students’ mental health and what enabled this nationwide data collection. By analyzing its driving forces, this paper reveals the ecology of power being forged at the intersection of multinational pharmaceutical companies, mental health experts, and the Korean government in the 2000s. The paper argues that, against the backdrop of the growing market for multinational pharmaceutical companies in South Korea, the rise in school violence became the catalyst for bringing old and new governmental tools, plans, and resources, putting all students under mental health screening. It shows the continuity as well as the transformation of developmental governmentality in a broader social change of South Korea under the influence of globalization. By doing so, the paper illuminates the shaping of the governmental technology – which was developed rather than imported and deployed rather than recommended – that enabled the nationwide collection of students’ data in the context of globalizing and politicizing ideas and practices in mental health.
Looking back: a review of policy implications for exercise oncology
Authors: Kennedy Mary A , Potiaumpai Melanie , Maitin-Shepard Melissa , Wilson Christopher M , Campbell Anna , Schwartz Anna L , Gorzelitz Jessica , Caru Maxime , Grimmett Chloe , Schmitz Kathryn H
Published: May 2023

The evidence to support the benefits of exercise for people living with and beyond cancer is robust. Still, exercise oncology interventions in the United States are only eligible for coverage by third-party payers within the restrictions of cancer rehabilitation settings. Without expanded coverage, access will remain highly inequitable, tending toward the most well-resourced. This article describes the pathway to third-party coverage for 3 programs that address a chronic disease and utilize exercise professionals: the Diabetes Prevention Program, Supervised Exercise Training for Peripheral Artery Disease, and Cancer Rehabilitation. Lessons learned will be applied toward expanding third-party coverage for exercise oncology programming.
Evaluation of Clinical Case Definitions for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Young Children
Authors: Englund Janet A , Cohen Rachel A , Bianco Veronique , Domachowske Joseph B , Langley Joanne M , Madhi Shabir A , Zaman Khalequ , Bueso Agustin , Ceballos Ana , Cousin Luis , Gandhi Sanjay , Gruselle Olivier , Jose Lisa , Klein Nicola P , Koen Anthonet , Puthanakit Thanyawee , Shi Meng , Silas Peter , Tangsathapornpong Auchara , Teeratakulpisarn Jamaree , Vesikari Timo , Haars Gerco , Leach Amanda , Stoszek Sonia K , Dieussaert Ilse
Published: May 2023

Background

Various case definitions of respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) are currently proposed. We assessed the performance of 3 clinical case definitions against the World Health Organization definition recommended in 2015 (WHO 2015).

Methods

In this prospective cohort study conducted in 8 countries, 2401 children were followed up for 2 years from birth. Suspected LRTIs were detected via active and passive surveillance, followed by in-person clinical evaluation including single timepoint respiratory rate and oxygen saturation (by pulse oximetry) assessment, and nasopharyngeal sampling for RSV testing by polymerase chain reaction. Agreement between case definitions was evaluated using Cohen’s κ statistics.

Results

Of 1652 suspected LRTIs, 227 met the WHO 2015 criteria for RSV-LRTI; 73 were classified as severe. All alternative definitions were highly concordant with the WHO 2015 definition for RSV-LRTI (κ: 0.95–1.00), but less concordant for severe RSV-LRTI (κ: 0.47–0.82). Tachypnea was present for 196/226 (86.7%) WHO 2015 RSV-LRTIs and 168/243 (69.1%) LRTI/bronchiolitis/pneumonia cases, clinically diagnosed by nonstudy physicians. Low oxygen saturation levels were observed in only 55/226 (24.3%) WHO 2015 RSV-LRTIs.

Conclusions

Three case definitions for RSV-LRTI showed high concordance with the WHO 2015 definition, while agreement was lower for severe RSV-LRTI. In contrast to increased respiratory rate, low oxygen saturation was not a consistent finding in RSV-LRTIs and severe RSV-LRTIs. This study demonstrates that current definitions are highly concordant for RSV-LRTIs, but a standard definition is still needed for severe RSV-LRTI.

Clinical trial registration

NCT01995175.
Multi-isocenter VMAT craniospinal irradiation using feasibility dose–volume histogram-guided auto-planning technique
Authors: Zhang Yun , Huang Yuling , Lin Jiafan , Ding Shenggou , Gong Xiaochang , Liu Qiegen , Gong Changfei
Published: May 2023

This study aims to propose a novel treatment planning methodology for multi-isocenter volumetric modulated arc therapy (VMAT) craniospinal irradiation (CSI) using the special feasibility dose–volume histogram (FDVH)-guided auto-planning (AP) technique. Three different multi-isocenter VMAT -CSI plans were created, including manually based plans (MUPs), conventional AP plans (CAPs) and FDVH-guided AP plans (FAPs). The CAPs and FAPs were specially designed by combining multi-isocenter VMAT and AP techniques in the Pinnacle treatment planning system. Specially, the personalized optimization parameters for FAPs were generated using the FDVH function implemented in PlanIQ software, which provides the ideal organs at risk (OARs) sparing for the specific anatomical geometry based on the valuable assumption of the dose fall-off. Compared to MUPs, CAPs and FAPs significantly reduced the dose for most of the OARs. FAPs achieved the best homogeneity index (0.092 ± 0.013) and conformity index (0.980 ± 0.011), while CAPs were slightly inferior to the FAPs but superior to the MUPs. As opposed to MUPs, FAPs delivered a lower dose to OARs, whereas the difference between FAPs and CAPs was not statistically significant except for the optic chiasm and inner ear_L. The two AP approaches had similar MUs, which were significantly lower than the MUPs. The planning time of FAPs (145.00 ± 10.25 min) was slightly lower than that of CAPs (149.83 ± 14.37 min) and was substantially lower than that of MUPs (157.92 ± 16.11 min) with P < 0.0167. Overall, introducing the multi-isocenter AP technique into VMAT-CSI yielded positive outcomes and may play an important role in clinical CSI planning in the future.
Participant- and Disease-Related Factors as Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Clinical Trial: A Multivariable Regression Analysis
Authors: Martin-Loeches Ignacio , Shorr Andrew F , Kollef Marin H , Du Jiejun , Losada Maria C , Paschke Amanda , DeRyke C Andrew , Wong Michael , Jensen Erin H , Chen Luke F
Published: May 2023

Background

In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was noninferior to piperacillin/tazobactam in treating hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. This post hoc analysis was conducted to determine independent predictors of efficacy outcomes in the RESTORE-IMI 2 trial, to assist in treatment decision making.

Methods

A stepwise multivariable regression analysis was conducted to identify variables that were independently associated with day 28 all-cause mortality (ACM), favorable clinical response at early follow-up (EFU), and favorable microbiologic response at end of treatment (EOT). The analysis accounted for the number of baseline infecting pathogens and in vitro susceptibility to randomized treatment.

Results

Vasopressor use, renal impairment, bacteremia at baseline, and Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scores ≥15 were associated with a greater risk of day 28 ACM. A favorable clinical response at EFU was associated with normal renal function, an APACHE II score <15, no vasopressor use, and no bacteremia at baseline. At EOT, a favorable microbiologic response was associated with IMI/REL treatment, normal renal function, no vasopressor use, nonventilated pneumonia at baseline, intensive care unit admission at randomization, monomicrobial infections at baseline, and absence of Acinetobacter calcoaceticus-baumannii complex at baseline. These factors remained significant after accounting for polymicrobial infection and in vitro susceptibility to assigned treatment.

Conclusions

This analysis, which accounted for baseline pathogen susceptibility, validated well-recognized patient- and disease-related factors as independent predictors of clinical outcomes. These results lend further support to the noninferiority of IMI/REL to piperacillin/tazobactam and suggests that pathogen eradication may be more likely with IMI/REL.

Clinical Trials Registration

NCT02493764.