bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting individual muscle fatigue tolerance by resting-state EEG brain network
*
Authors: Li Zhiwei , Yi Chanlin , Chen Chunli , Liu Chen , Zhang Shu , Li Shunchang , Gao Dongrui , Cheng Liang , Zhang Xiabing , Sun Junzhi , He Ying , Xu Peng
Published: July 2022

Objective. Exercise-induced muscle fatigue is a complex physiological phenomenon involving the central and peripheral nervous systems, and fatigue tolerance varies across individuals. Various studies have emphasized the close relationships between muscle fatigue and the brain. However, the relationships between the resting-state electroencephalogram (rsEEG) brain network and individual muscle fatigue tolerance remain unexplored. Approach. Eighteen elite water polo athletes took part in our experiment. Five-minute before- and after-fatigue-exercise rsEEG and fatiguing task (i.e. elbow flexion and extension) electromyography (EMG) data were recorded. Based on the graph theory, we constructed the before- and after-task rsEEG coherence network and compared the network differences between them. Then, the correlation between the before-fatigue rsEEG network properties and the EMG fatigue indexes when a subject cannot keep on exercising anymore was profiled. Finally, a prediction model based on the before-fatigue rsEEG network properties was established to predict fatigue tolerance. Main results. Results of this study revealed the significant differences between the before- and after-exercise rsEEG brain network and found significant high correlations between before-exercise rsEEG network properties in the beta band and individual muscle fatigue tolerance. Finally, an efficient support vector regression (SVR) model based on the before-exercise rsEEG network properties in the beta band was constructed and achieved the accurate prediction of individual fatigue tolerance. Similar results were also revealed on another 30 subject swimmer data set further demonstrating the reliability of predicting fatigue tolerance based on the rsEEG network. Significance. Our study investigates the relationship between the rsEEG brain network and individual muscle fatigue tolerance and provides a potential objective physiological biomarker for tolerance prediction and the regulation of muscle fatigue.
Nonlinear MHD modeling of n
= 1 RMP-induced pedestal transport and mode coupling effects on ELM suppression in KSTAR
Authors: Kim S.K. , Pamela S. , Logan N.C. , Na Y.-S. , Lee C.Y. , Park J.-K. , Yang S.M. , Hu Q. , Becoulet M. , Huijsmans G. , Hoelzl M. , In Y. , Kim M.W. , Lee H.H. , Lee J. , Lee J.H. , Kwon O. , Kolemen E. , the JOREK Team
Published: July 2022

Fully suppressing edge-localized modes (ELMs), e.g., with resonant magnetic perturbations (RMPs), is essential to reach and sustain high-performance steady-state H-mode plasmas because large ELMs can significantly reduce the lifetime of divertor components in future tokamak reactors. RMP-driven ELM suppression in KSTAR has been modeled by coupling the neoclassical transport code PENTRC to the nonlinear 3D MHD code JOREK. We have found that the radial transport from the combined effects of the kink-peeling, tearing response, and neoclassical toroidal viscosity can explain the pedestal degradation observed in experiments. In addition, it has been found that the RMP response can increase the inter-ELM heat flux on the lower outer divertor by redistributing the heat transport between the divertor plates. In addition to the degraded pedestal, ELM suppression is also attributable to the RMP-induced mode interactions. While the linear stability of peeling-ballooning mode (PBMs) improves owing to the degraded pedestal, the PBM and RMP interaction increases the spectral transfer between edge harmonics, preventing catastrophic growth and the crash of unstable modes. Here, it turns out that the magnetic islands near the pedestal top can play a vital role in mediating the mode interactions.
Dynamics Near the Subcritical Transition of the 3D Couette Flow II: Above Threshold Case
Authors: Bedrossian Jacob , Germain Pierre , Masmoudi Nader
Published: July 2022

This is the second in a pair of works which study small disturbances to the plane, periodic 3D Couette flow in the incompressible Navier-Stokes equations at high Reynolds number Re. In this work, we show that there is constant

0
>

c
0

≪
1

0 > c_0 \ll 1

, independent of

R
e

\mathbf {Re}

, such that sufficiently regular disturbances of size

ϵ
≲

R
e

−
2

/

3
−
δ

\epsilon \lesssim \mathbf {Re}^{-2/3-\delta }

for any

δ
>
0

\delta > 0

exist at least until

t
=

c
0

ϵ

−
1

t = c_0\epsilon ^{-1}

and in general evolve to be

O
(

c
0

)

O(c_0)

due to the lift-up effect. Further, after times

t
≳

R
e

1

/

3

t \gtrsim \mathbf {Re}^{1/3}

, the streamwise dependence of the solution is rapidly diminished by a mixing-enhanced dissipation effect and the solution is attracted back to the class of “2.5 dimensional” streamwise-independent solutions (sometimes referred to as “streaks”). The largest of these streaks are expected to eventually undergo a secondary instability at

t
≈

ϵ

−
1

t \approx \epsilon ^{-1}

. Hence, our work strongly suggests, for all (sufficiently regular) initial data, the genericity of the “lift-up effect

⇒
\Rightarrow

streak growth

⇒
\Rightarrow

streak breakdown” scenario for turbulent transition of the 3D Couette flow near the threshold of stability forwarded in the applied mathematics and physics literature.
Assessment of burnout and pandemic fatigue among pharmacy leadership in the Veterans Health Administration healthcare system
Authors: Mathew Annita E , Nelson Jordan D , Rasmussen Mary , Ourth Heather
Published: July 2022

Purpose

Factors associated with burnout in Veterans Health Administration (VHA) pharmacy leadership positions were examined during the coronavirus disease 2019 (COVID-19) pandemic.

Methods

A questionnaire was distributed to all pharmacy executives of the VHA healthcare system. It collected demographic and employment characteristics, career satisfaction and work-related variables, indicators of burnout using validated single-item measures adapted from the Maslach Burnout Inventory, and the impact of the COVID-19 pandemic on psychosocial and work-related variables. A χ2 test with Bonferroni correction was used to evaluate the data. Burnout was defined as a score of 4 or greater on either of the 2 single-item validated statements adapted from the Maslach Burnout Inventory to assess emotional exhaustion and depersonalization.

Results

In total, 407 (of 1,027; 39.6%) VHA pharmacy leaders representing Veterans Integrated Service Network pharmacy executives, chiefs of pharmacy, associate chiefs of pharmacy, and inpatient and outpatient supervisors completed the survey. The overall prevalence of burnout was 68.6% using the aggregate measure of emotional exhaustion or depersonalization. Pharmacy leaders who worked more than 60 hours a week reported significantly greater rates of burnout than those who worked 40 to 60 hours a week (86.7% vs 66.9%, χ2 = 7.34, degrees of freedom = 1, P < 0.05). Those experiencing increased workload related to COVID-19 also reported high burnout rates (72.1%, χ2 = 16.40, degrees of freedom = 1, P < 0.001). Burnout scores were similar across groups when respondents were stratified by leadership position, gender, age, or years in position.

Conclusion

As of March 2021, two-thirds of pharmacy leaders were experiencing burnout. It is important for healthcare system leadership to identify patterns of burnout among their pharmacy leaders to ensure a productive and sustainable workforce.
GLOBE: a contrastive learning-based framework for integrating single-cell transcriptome datasets
Authors: Yan Xuhua , Zheng Ruiqing , Li Min
Published: July 2022

Integration of single-cell transcriptome datasets from multiple sources plays an important role in investigating complex biological systems. The key to integration of transcriptome datasets is batch effect removal. Recent methods attempt to apply a contrastive learning strategy to correct batch effects. Despite their encouraging performance, the optimal contrastive learning framework for batch effect removal is still under exploration. We develop an improved contrastive learning-based batch correction framework, GLOBE. GLOBE defines adaptive translation transformations for each cell to guarantee the stability of approximating batch effects. To enhance the consistency of representations alignment, GLOBE utilizes a loss function that is both hardness-aware and consistency-aware to learn batch effect-invariant representations. Moreover, GLOBE computes batch-corrected gene matrix in a transparent approach to support diverse downstream analysis. Benchmarking results on a wide spectrum of datasets show that GLOBE outperforms other state-of-the-art methods in terms of robust batch mixing and superior conservation of biological signals. We further apply GLOBE to integrate two developing mouse neocortex datasets and show GLOBE succeeds in removing batch effects while preserving the contiguous structure of cells in raw data. Finally, a comprehensive study is conducted to validate the effectiveness of GLOBE.
Coupling of Physical and Chromatographic Separation for Analyzing Cream Containing Miconazole, Mometasone Furoate and Gentamicin Sulphate
Authors: Tawakkol Shereen Mostafa , Fayez Yasmin Mohammed , Fahmy Nesma Mahmoud , Lotfy Hayam Mahmoud , Shehata Mostafa Abdel-Atty
Published: July 2022

High-performance liquid chromatographic method was developed, validated and applied for miconazole, mometasone and gentamicin in Momenta® cream. Physical separation was applied using two extraction procedures due to different solubility of the three components. First, a methanolic extract of the cream contained miconazole and mometasone was chromatographed on ODS-3 Inertsil C18 column (150 × 4.6, 5 μm) using acetonitrile: water (80:20, v/v) as a mobile phase, flow rate 1.5 mL·min−1, scanned at 230 nm, showing tR 2.817 and 6.808 min for mometasone and miconazole, respectively. Second, an aqueous extract of the cream containing gentamicin was derivatized with o-phthalaldehyde in order to enhance the gentamicin UV detection and subjected to ion pairing chromatography on Inertsil ODS-3 C18 column (150 × 4.6, 5 μm), using methanol: 0.025 M heptane sulphonic acid: glacial acetic acid (75:20:5, by volume) as a mobile phase, flow rate 0.8 mL·min−1, scanned at 330 nm where the three active gentamicin isomers were separated at tR 11.7, 15.6 and 18.3 min. Suitability of this method for quantitative estimation of the drugs was proved by validation according to ICH guidelines. The method was selective, precise and accurate so could be used for analysis of cream formulation in QC labs.
Patient-reported outcomes in the aging population of adults with congenital heart disease: results from APPROACH-IS
Authors: Moons Philip , Luyckx Koen , Thomet Corina , Budts Werner , Enomoto Junko , Sluman Maayke A , Yang Hsiao-Ling , Jackson Jamie L , Khairy Paul , Cook Stephen C , Chidambarathanu Shanthi , Alday Luis , Oechslin Erwin , Eriksen Katrine , Dellborg Mikael , Berghammer Malin , Johansson Bengt , Mackie Andrew S , Menahem Samuel , Caruana Maryanne , Veldtman Gruschen , Soufi Alexandra , Fernandes Susan M , White Kamila , Callus Edward , Kutty Shelby , Kovacs Adrienne H ,   the APPROACH-IS consortium, Alday Luis , Maisuls Héctor , Vega Betina , Menahem Samuel , Eaton Sarah , Wang Qi Feng , Larion Ruth , Budts Werner , Deyk Kristien Van , Apers Silke , Goossens Eva , Rassart Jessica , Luyckx Koen , Moons Philip , Rempel Gwen , Mackie Andrew , Ballantyne Ross , Rankin Kathryn , Norris Colleen , Taylor Dylan , Vondermuhll Isabelle , Windram Jonathan , Heggie Pamela , Lasiuk Gerri , Khairy Paul , Proietti Anna , Dore Annie , Mercier Lise-Andrée , Mongeon François-Pierre , Marcotte François , Ibrahim Reda , Mondésert Blandine , Côté Marie-Claude , Kovacs Adrienne , Oechslin Erwin , Bandyopadhyay Mimi , Soufi Alexandra , Filippo Sylvie Di , Sassolas François , Bozio André , Chareyras Cécile , Chidambarathanu Shanthi , Farzana Farida , Lakshmi Nitya , Callus Edward , Quadri Emilia , Chessa Massimo , Campioni Giovanna , Giamberti Alessandro , Enomoto Junko , Mizuno Yoshiko , Caruana Maryanne , Grech Victor , Vella Sheena , Mifsud Anabel , Borg Neville , Chircop Daniel , Balbi Matthew Mercieca , Critien Rachel Vella , Farrugia James , Gatt Yanika , Muscat Darlene , Eriksen Katrine , Estensen Mette-Elise , Dellborg Mikael , Berghammer Malin , Mattsson Eva , Strandberg Anita , Karlström-Hallberg Pia , Johansson Bengt , Kronhamn Anna-Karin , Schwerzman Markus , Thomet Corina , Huber Margrit , Wang Jou-Kou , Lu Chun-Wei , Yang Hsiao-Ling , Hua Yu Chuan , Mulder Barbara , Sluman Maayke , Post Marco , Pieper Els , Peels Kathinka , Waskowsky Marc , Veldtman Gruschen , Faust Michelle , Lozier Colin , Reed Christy , Hilfer Jamie , Daniels Curt , Jackson Jamie , Kutty Shelby , Chamberlain Carolyn , Warta Sara , Cook Stephen , Hindes Morgan , Cedars Ari , White Kamila , Fernandes Susan , Romfh Anitra , MacMillen Kirstie
Published: July 2022

The congenital heart disease (CHD) population now comprises an increasing number of older persons in their 6th decade of life and beyond. We cross-sectionally evaluated patient-reported outcomes (PROs) in persons with CHD aged 60 years or older, and contrasted these with PROs of younger patients aged 40–59 years and 18–39 years. Adjusted for demographic and medical characteristics, patients ≥60 years had a lower Physical Component Summary, higher Mental Component Summary, and lower anxiety (Hospital Anxiety and Depression Scale-Anxiety) scores than patients in the two younger categories. For satisfaction with life, older persons had a higher score than patients aged 40–59 years.

Registration: ClinicalTrials.gov NCT02150603.
Heterologous biosynthesis of taraxerol by engineered Saccharomyces cerevisiae
Authors: Tan Jinxiu , Zhang Chuanbo , Pai Huihui , Lu Wenyu
Published: July 2022

Taraxerol is an oleanane-type pentacyclic triterpenoid compound distributed in many plant species that has good effects on the treatment of inflammation and tumors. However, the taraxerol content in medicinal plants is low, and chemical extraction requires considerable energy and time, so taraxerol production is a problem. It is a promising strategy to produce taraxerol by applying recombinant microorganisms. In this study, a Saccharomyces cerevisiae strain WKde2 was constructed to produce taraxerol with a titer of 1.85 mg·l–1, and the taraxerol titer was further increased to 12.51 mg·l–1 through multiple metabolic engineering strategies. The endoplasmic reticulum (ER) size regulatory factor INO2, which was reported to increase squalene and cytochrome P450-mediated 2,3-oxidosqualene production, was overexpressed in this study, and the resultant strain WTK11 showed a taraxerol titer of 17.35 mg·l–1. Eventually, the highest reported titer of 59.55 mg·l–1 taraxerol was achieved in a 5 l bioreactor. These results will serve as a general strategy for the production of other triterpenoids in yeast.
Individual differences and compliance intentions with COVID-19 restrictions: insights from a lockdown in Melbourne (Australia)
Authors: Auton Jaime C , Sturman Daniel
Published: July 2022

The coronavirus (COVID-19) pandemic has caused an international public health and economic crisis. Despite the COVID-19 vaccine rollout in many countries from late 2020, non-pharmaceutical interventions are still required to minimize the spread of the virus. However, notable variation in voluntary compliance with these interventions has been reported. This study investigated various individual differences associated with intentions to comply with COVID-19 restrictions during a sustained (112 day) lockdown in Melbourne (Australia) in late 2020. Participants (N = 363) completed an online survey where they responded to various socio-demographic, health and psychological questions. Participants also responded to a series of vignettes that assessed their intended behaviour in specific situations and their knowledge of the current COVID-19 restrictions. Overall, it was found that greater levels of organization predicted greater intentions to comply with the COVID-19 restrictions, while higher socio-economic status, sociability and anxiety predicted lower compliance intentions. Further, individuals previously diagnosed with COVID-19 reported lower intentions to comply with the COVID-19 restrictions. The strongest predictor of compliance intentions, however, was a greater knowledge of the current restrictions. These findings highlight that public health orders around COVID-19 restrictions should be presented in a clear and uncomplicated manner and should target specific groups to increase compliance.
Barriers to health promotion strategy work in Finnish municipalities
Authors: Leinonen Jaana , Syväjärvi Antti
Published: July 2022

This study’s aim is to increase insights into the characteristics and conditions of municipal health promotion strategy work. Specifically, we aim to find barriers connected to strategy work, that is, creating and formulating municipal health promotion strategy documents, with the following empirical research question: What perceptions do municipal health promotion strategy actors have on barriers connected to low citizen participation, narrow cross-departmental collaboration and weak goal orientation in health promotion strategy work? Empirical data comprised 22 thematics, individual interviews collected from municipal managers, sector managers and municipal health coordinators. Analysis was conducted using content analysis. This study’s findings showed that the main barriers impeding optimal strategy work conditions were administrators’ sceptical views of participation and undeveloped administrative practices in inclusive citizen participation, inadequate leadership to unite actors and facilitate collaborative strategy work practices, and challenges in integrating various views into coherent strategic goals. Also, a need for boundary-spanning leadership that strengthens mutual interaction and creates a shared understanding of health promotion to build strategic collaboration and goal-oriented strategy work was revealed. Finally, to strengthen this leadership, influencing administrators’ mindsets, behaviour and administrative culture is imperative.
Involvement of histone deacetylase CsHDA2 in regulating (E)-nerolidol formation in tea (Camellia sinensis) exposed to tea green leafhopper infestation
Authors: Gu Dachuan , Wu Shuhua , Yu Zhenming , Zeng Lanting , Qian Jiajia , Zhou Xiaochen , Yang Ziyin
Published: July 2022

Herbivore-induced plant volatiles (HIPVs) help the tea plant (Camellia sinensis) adapt to environmental stress, and they are also quality-related components of tea. However, the upstream mechanism regulating the herbivore-induced expression of volatile biosynthesis genes is unclear, especially at the level of epigenetic regulation. In this study, similar to the effects of a tea green leafhopper infestation, treatments with exogenous jasmonic acid (JA) and histone deacetylase inhibitors significantly increased the (E)-nerolidol content in tea and induced the expression of the associated biosynthesis gene CsNES. Furthermore, a key transcription factor related to JA signaling, myelocytomatosis 2 (CsMYC2), interacted with histone deacetylase 2 (CsHDA2) in vitro and in vivo. A tea green leafhopper infestation inhibited CsHDA2 expression and decreased CsHDA2 abundance. Moreover, the tea green leafhopper infestation increased H3 and H4 acetylation levels in the promoter region of CsNES, which in turn upregulated the expression of CsNES and increased the (E)-nerolidol content. In this study, we revealed the effects of histone acetylations on the accumulation of HIPVs, while also confirming that CsHDA2–CsMYC2 is an important transcriptional regulatory module for the accumulation of (E)-nerolidol induced by tea green leafhoppers. The results of this study may be useful for characterizing plant aromatic compounds and the main upstream stress-responsive signaling molecules. Furthermore, the study findings will assist researchers clarify the epigenetic regulation influencing plant secondary metabolism in response to external stress.
The use of objective assessments in the evaluation of technical skills in cardiothoracic surgery: a systematic review
Authors: Hussein Nabil , Van den Eynde Jef , Callahan Connor , Guariento Alvise , Gollmann-Tepeköylü Can , Elbatarny Malak , Loubani Mahmoud
Published: July 2022

OBJECTIVES

With reductions in training time and intraoperative exposure, there is a need for objective assessments to measure trainee progression. This systematic review focuses on the evaluation of trainee technical skill performance using objective assessments in cardiothoracic surgery and its incorporation into training curricula.

METHODS

Databases (EBSCOHOST, Scopus and Web of Science) and reference lists of relevant articles for studies that incorporated objective assessment of technical skills of trainees/residents in cardiothoracic surgery were included. Data extraction included task performed; assessment setting and tool used; number/level of assessors; study outcome and whether the assessments were incorporated into training curricula. The methodological rigour of the studies was scored using the Medical Education Research Study Quality Instrument (MERSQI).

RESULTS

Fifty-four studies were included for quantitative synthesis. Six were randomized-controlled trials. Cardiac surgery was the most common speciality utilizing objective assessment methods with coronary anastomosis the most frequently tested task. Likert-based assessment tools were most commonly used (61%). Eighty-five per cent of studies were simulation-based with the rest being intraoperative. Expert surgeons were primarily used for objective assessments (78%) with 46% using blinding. Thirty (56%) studies explored objective changes in technical performance with 97% demonstrating improvement. The other studies were primarily validating assessment tools. Thirty-nine per cent of studies had established these assessment tools into training curricula. The mean ± standard deviation MERSQI score for all studies was 13.6 ± 1.5 demonstrating high validity.

CONCLUSIONS

Despite validated technical skill assessment tools being available and demonstrating trainee improvement, their regular adoption into training curricula is lacking. There is a need to incorporate these assessments to increase the efficiency and transparency of training programmes for cardiothoracic surgeons.
Simplicity of Higher Rank TripletW-Algebras
Authors: Sugimoto Shoma
Published: July 2022

We show that the higher rank triplet $W$-algebra $W_{\sqrt {p}Q}$ is simple for $p\geq h-1$. Furthermore, we show that the $W_{\sqrt {p}Q}$-module $W_{\sqrt {p}(Q-\lambda _0)+\lambda _p}$ introduced in [21] is simple if $\sqrt {p}\lambda _p$ is in the closure of the fundamental alcove and give the decomposition as a direct sum of simple $\boldsymbol {W}_{p-h}({\mathfrak {g}})$-modules.
Sharp Bound for the Fourth Moment of Holomorphic Hecke Cusp Forms
Authors: Zenz Peter
Published: July 2022

We prove that the fourth moment of holomorphic Hecke cusp forms is bounded by a constant provided that the Generalized Riemann Hypothesis holds. We accomplish this using Watson’s formula, which translates the question in hand into a moment problem for $L$-functions that is amenable to the techniques of Soundararajan and Harper on obtaining sharp bounds for moments of the Riemann zeta function.
The Virasoro-Like Algebra of a Frobenius Manifold
Authors: Liu Si-Qi , Yang Di , Zhang Youjin , Zhou Jian
Published: July 2022

For an arbitrary calibrated Frobenius manifold, we construct an infinite dimensional Lie algebra, called the Virasoro-like algebra, which is a deformation of the Virasoro algebra of the Frobenius manifold. By using the Virasoro-like algebra we give a family of quadratic PDEs that are satisfied by the genus-zero free energy of the Frobenius manifold. We also derive, under the semisimplicity assumption, the Virasoro constraints for the corresponding abstract Hodge partition function.
A hybrid model to study how late long-term potentiation is affected by faulty molecules in an intraneuronal signaling network regulating transcription factor CREB
Authors: Emadi Ali , Ozen Mustafa , Abdi Ali
Published: July 2022

Systems biology analysis of intracellular signaling networks has tremendously expanded our understanding of normal and diseased cell behaviors and has revealed paths to finding proper therapeutic molecular targets. When it comes to neurons in the human brain, analysis of intraneuronal signaling networks provides invaluable information on learning, memory and cognition-related disorders, as well as potential therapeutic targets. However, neurons in the human brain form a highly complex neural network that, among its many roles, is also responsible for learning, memory formation and cognition. Given the impairment of these processes in mental and psychiatric disorders, one can envision that analyzing interneuronal processes, together with analyzing intraneuronal signaling networks, can result in a better understanding of the pathology and, subsequently, more effective target discovery. In this paper, a hybrid model is introduced, composed of the long-term potentiation (LTP) interneuronal process and an intraneuronal signaling network regulating CREB. LTP refers to an increased synaptic strength over a long period of time among neurons, typically induced upon occurring an activity that generates high-frequency stimulations (HFS) in the brain, and CREB is a transcription factor known to be highly involved in important functions of the cognitive and executive human brain such as learning and memory. The hybrid LTP-signaling model is analyzed using a proposed molecular fault diagnosis method. It allows to study the importance of various signaling molecules according to how much they affect an intercellular phenomenon when they are faulty, i.e. dysfunctional. This paper is intended to suggest another angle for understanding the pathology and therapeutic target discovery by classifying and ranking various intraneuronal signaling molecules based on how much their faulty behaviors affect an interneuronal process. Possible relations between the introduced hybrid analysis and the previous purely intracellular analysis are investigated in the paper as well.
HIV-1 subtype F integrase polymorphisms external to the catalytic core domain contribute to severe loss of replication capacity in context of the integrase inhibitor resistance mutation Q148H
Authors: Aulicino Paula C , Momin Zoha , Rozenszajn Mijael , Monzon Arturo , Arazi-Caillaud Solange , Bologna Rosa , Mangano Andrea , Kimata Jason T
Published: July 2022

Background

In prior studies, HIV-1 BF recombinants with subtype F integrases failed to develop resistance to raltegravir through the Q148H mutational pathway. We aimed to determine the role of subtype-specific polymorphisms in integrase on drug susceptibility, viral replication and integration.

Methods

Integrase sequences were retrieved from the Los Alamos Database or obtained from the Garrahan HIV cohort. HIV-1 infectious molecular clones with or without Q148H (+ G140S) resistance mutations were constructed using integrases of subtype B (NL4-3) or F1(BF) ARMA159 and URTR23. Integrase chimeras were generated by reciprocal exchanges of a 200 bp fragment spanning amino acids 85–150 of the catalytic core domain (CCD) of NL4-3-Q148H and either ARMA159-Q148H or URTR23-Q148H. Viral infections were quantified by p24 ELISA and Alu-gag integration PCR assay.

Results

At least 18 different polymorphisms distinguish subtype B from F1(BF) recombinant integrases. In phenotypic experiments, p24 at Day 15 post-infection was high (105–106 pg/mL) for WT and NL4-3-Q148H; by contrast, it was low (102–104 pg/mL) for both F1(BF)-Q148H + G140S viruses, and undetectable for the Q148H mutants. Compared with WT viruses, integrated DNA was reduced by 5-fold for NL4-3-Q148H (P = 0.05), 9-fold for URTR23-Q148H (P = 0.01) and 16000-fold for ARMA159-Q148H (P = 0.01). Reciprocal exchange between B and F1(BF) of an integrase CCD region failed to rescue the replicative defect of F1(BF) integrase mutants.

Conclusions

The functional impairment of Q148H in the context of subtype F integrases from BF recombinants explains the lack of selection of this pathway in vivo. Non-B polymorphisms external to the integrase CCD may influence the pathway to integrase strand transfer inhibitor resistance.
Advanced Spectrophotometric Resolution Techniques for a Spectrally Overlapping Spasmolytic Binary Mixture along with Dichloroaniline as a Toxic Impurity: Application to Content Uniformity Testing
Authors: Darweish Eman , Marzouk Hoda M , Fayez Yasmin M , Eissa Maya S
Published: July 2022

Background

Irritable bowel syndrome (IBS) is a common disorder leading to undesirable pain. Phloroglucinol (PHG) and trimethylphloroglucinol (TMG) are co-formulated as spasmolytic medication that is considered to be effective in reducing smooth muscle spasm. 3,5-Dichloroaniline (DCL) is a specified PHG pharmacopoeial impurity which needs to be monitored to avoid its toxic effects.

Objective

Different smart approaches are presented to provide simple, reliable, and economic spectrophotometric methods able to resolve the severe overlap in the spectra of PHG and TMG in their pure and pharmaceutical forms, in addition to their estimation in the presence of DCL as a toxic impurity of PHG without any need for initial separation.

Methods

The presented work includes univariate methods, derivative ratio (DR), ratio difference (RD), mean centering (MCR) and deconvulated Fourier method (DF), which were able to determine PHG and TMG simultaneously in their binary mixture. Firstly, DCL was estimated in the zero order, where the two drugs have zero absorption at 247.0 nm, and then its contribution was eliminated by applying ratio subtraction method. Multivariate chemometric partial least squares (PLS) and principal component regression (PCR) models were also applied to determine PHG and TMG simultaneously in the presence of the impurity, DCL

Results

Univariate methods were applied in the range 5.0–30.0, 2.5–25.0, and 1.0–12.0 µg/mL for PHG, TMG, and DCL, respectively. The proposed chemometric models were used in the range 6.0–14.0, 5.0–25.0 and 2.0–10.0 µg/mL for PHG, TMG, and DCL, respectively. These analytical approaches succeeded in estimating the cited drugs in their pharmaceutical formulation and assessing content uniformity of dosage units. The methods were statistically compared with a reported HPLC method, and the results revealed no significance statistical difference.

Conclusion

This work provides for the first time successful univariate and multivariate PLS and PCR methods to assess PHG and TMG in the presence of DCL as a toxic impurity along with content uniformity testing of dosage units.

Highlights

Comparative univariate and multivariate spectrophotometric analytical approaches are presented, for the first time, for estimation of spasmolytic formulation of PHG and TMG in the presence of DCL as a PHG toxic impurity. Successful application to content uniformity testing of Stopspasm® dosage form is demonstrated. A statistical study, including t-tests and one-way analysis of variance (ANOVA), was conducted.
Listening to the Patient Voice Adds Value to Cancer Clinical Trials
Authors: Brundage Michael D , Crossnohere Norah L , O’Donnell Jennifer , Cruz Rivera Samantha , Wilson Roger , Wu Albert W , Moher David , Kyte Derek , Reeve Bryce B , Gilbert Alexandra , Chen Ronald C , Calvert Melanie J , Snyder Claire
Published: July 2022

Randomized clinical trials are critical for evaluating the safety and efficacy of interventions in oncology and informing regulatory decisions, practice guidelines, and health policy. Patient-reported outcomes (PROs) are increasingly used in randomized trials to reflect the impact of receiving cancer therapies from the patient perspective and can inform evaluations of interventions by providing evidence that cannot be obtained or deduced from clinicians’ reports or from other biomedical measures. This commentary focuses on how PROs add value to clinical trials by representing the patient voice. We employed 2 previously published descriptive frameworks (addressing how PROs are used in clinical trials and how PROs have an impact, respectively) and selected 9 clinical trial publications that illustrate the value of PROs according to the framework categories. These include 3 trials where PROs were a primary trial endpoint, 3 trials where PROs as secondary endpoints supported the primary endpoint, and 3 trials where PROs as secondary endpoints contrast the primary endpoint findings in clinically important ways. The 9 examples illustrate that PROs add valuable data to the care and treatment context by informing future patients about how they may feel and function on different treatments and by providing clinicians with evidence to support changes to clinical practice and shared decision making. Beyond the patient and clinician, PROs can enable administrators to consider the cost-effectiveness of implementing new interventions and contribute vital information to policy makers, health technology assessors, and regulators. These examples provide a strong case for the wider implementation of PROs in cancer trials.
A survey of deuterated ammonia in the Cepheus star-forming region L1251
Authors: Galloway-Sprietsma Maria , Shirley Yancy L , Di Francesco James , Keown Jared , Scibelli Samantha , Sipilä Olli , Smullen Rachel
Published: July 2022

Understanding the chemical processes during starless core and prestellar core evolution is an important step in understanding the initial stages of star and disc formation. This project is a study of deuterated ammonia, o-NH2D, in the L1251 star-forming region towards Cepheus. Twenty-two dense cores (20 of which are starless or prestellar, and two of which have a protostar), previously identified by p-NH3 (1,1) observations, were targeted with the 12m Arizona Radio Observatory telescope on Kitt Peak. o-NH2D J$_{\rm {K_a} \rm {K_c}}^{\pm } =$$1_{11}^{+} \rightarrow 1_{01}^{-}$ was detected in 13 (59 per cent) of the NH3-detected cores with a median sensitivity of $\sigma _{T_{mb}} = 17$ mK. All cores detected in o-NH2D at this sensitivity have p-NH3 column densities >1014 cm−2. The o-NH2D column densities were calculated using the constant excitation temperature (CTEX) approximation while correcting for the filling fraction of the NH3 source size. The median deuterium fraction was found to be 0.11 (including 3σ upper limits). However, there are no strong, discernible trends in plots of deuterium fraction with any physical or evolutionary variables. If the cores in L1251 have similar initial chemical conditions, then this result is evidence of the cores physically evolving at different rates.
Home Smoke-Free Policies as Children Age: Urban, Rural, and Suburban Differences
Authors: Mantey Dale S , Omega-Njemnobi Onyinye , Hunt Ethan T , Lanza Kevin , Cristol Benjamin , Kelder Steven H
Published: July 2022

Introduction

Parents/guardians can effectively reduce tobacco smoking and secondhand smoke exposure among youth by adopting and enforcing rules against indoor tobacco smoking (ie, home smoke-free policies). We investigate home smoke-free policies from childhood to adolescence in the United States and across rural, suburban, and urban households.

Aims and Methods

We analyzed 2019–2020 National Survey of Children’s Health data from n = 5,955 parents of youth aged 0–17, living at home with a tobacco smoker in the United States (U.S). Geographical categories were: rural, suburban, and urban. Home smoke-free policy reflected prohibiting tobacco smoking inside the home. Weighted logistic regressions examined the (1) association between youth age and home smoke-free policies, (2) interaction between geographic category and youth age, and (3) differing associations between youth age and home smoke-free policies by geography. Models controlled for youth race, ethnicity, sex, parental education, household annual income, and home structure.

Results

Approximately 13.2% of U.S. households with a smoker did not have a home smoke-free policy. Stratified analyses found one-year increase in youth age was associated with lower odds of having a home smoke-free policy in rural (aOR:0.91; 95%CI: 0.87–0.95) and urban (aOR: 0.96; 95%CI: 0.92–1.00; p = .039), but not suburban (aOR:1.00; 95%CI: 0.95–1.05) households, controlling for covariates.

Conclusion

Odds of having a smoke-free home in the U.S. declined significantly in rural (9% per year) and urban (4%) but not suburban (0%) households. We quantify declines in home smoke-free policies as children age and identify geographic disparities for this environmental determinant of health.

Implications

Health promotion efforts targeting secondhand smoke prevention is needed, particularly for parents of older youth. Furthermore, there is a clear geographic bias in secondhand smoke exposure among all youth particularly older youth. Tailored interventions are needed to address geographic disparities in secondhand smoke exposure among rural and urban youth.
Reducing agency and social costs by keeping kids in school and out of the justice system: A cost–benefit analysis of the Philadelphia Police School Diversion Program
Authors: NeMoyer Amanda , Mai Chris , Kreimer Rena , Le TuQuynh , Pollard Angela , Goldstein Naomi E S
Published: July 2022

Growing recognition of the school-to-prison pipeline and its associated detrimental effects has spurred efforts aimed at reducing the rate of school-based arrests across the United States. One such initiative, the Philadelphia Police School Diversion Program, has demonstrated promising findings related to reduced numbers of school-based arrests and improved school outcomes among youth. However, without information about the financial costs and benefits associated with program operation, stakeholders may be hesitant to implement similar programming in other localities. Therefore, we conducted a cost–benefit analysis of the Philadelphia Police School Diversion Program. Results indicated that this diversion program produced approximately $1.6 million in inflation-adjusted net benefit in its first year of operation and approximately $1.9 million in inflation-adjusted net benefit in its fifth year of operation. Findings may inform decisions about program replication in other jurisdictions where stakeholders seek alternative school policing strategies.
Remaking the Sustainable Development Goals: relational Indigenous epistemologies
Authors: Waldmüller Johannes M , Yap Mandy , Watene Krushil
Published: July 2022

While the Sustainable Development Goals (SDGs) were inclusive in their design, the reliance on official measurement infrastructures has upheld narrow definitions of both the terms of sustainability and development. Indigenous and non-Indigenous “governance beyond the state” approaches call these definitions into question. They highlight that disaggregated official data are unable to fully reflect alternative grounds and aspirations of living sustainably with the environment and non-human world. Relational Indigenous epistemologies and practices contribute to alternative epistemic infrastructures. In this paper, three examples from the Andean-Pacific region provide an alternative lens through which to reconceptualize and remake the SDG landscape. Together this suite of cases highlights the importance of bottom-up articulation processes, knowledge inclusion, and alternative epistemic harmonization for operationalizing the SDGs. In particular, we highlight the urgent need to renegotiate the relationship between Indigenous communities and the global measurement infrastructure in order to pursue and realize global sustainability goals.
Comparative physiological and transcriptome analysis reveals the potential mechanism of selenium accumulation and tolerance to selenate toxicity of Broussonetia papyrifera
Authors: Chen Qiangwen , Yu Li , Chao Wei , Xiang Juan , Yang Xiaoyan , Ye Jiabao , Liao Xiaoli , Zhou Xian , Rao Shen , Cheng Shuiyuan , Cong Xin , Xiao Bo , Xu Feng
Published: July 2022

Broussonetia papyrifera is an important fodder tree that is widely distributed in China. Enhancing the selenium (Se) content in B. papyrifera may help to improve the nutritional value of the feed. In this study, sodium selenite and selenate were foliar applied to investigate the mechanisms of Se tolerance and accumulation in B. papyrifera. The results showed that both Se forms significantly increased the total Se content, and the proportion of organic Se was significantly higher in the sodium selenite treatment than in the control. In addition, the soluble sugar, phenolic acid and flavonoid contents and antioxidant enzyme activities were increased by exogenous Se. The de novo RNA sequencing results showed that 644 and 1804 differentially expressed genes were identified in the selenite and selenate comparison groups, respectively. Pathway enrichment analysis demonstrated that 24 of the 108 pathways were significantly enriched, of which sulfur assimilation genes in the sodium selenite-treated groups were upregulated, whereas Se conjugation and transporter genes, such as SBP1, PCS, GSTs, ABCs and GPX, were significantly induced under selenate treatment. The hub genes identified by weighted-gene co-expression network analysis further confirmed that sulfur assimilation, conjugation and transporter genes might play a vital role in Se assimilation and tolerance. From this, a model of Se metabolism in B. papyrifera was proposed based on the above physiological and RNA sequencing data. This study is the first study to report that B. papyrifera has a strong ability to accumulate and tolerate exogenous Se, thereby providing a foundation for further characterization of the accumulation and tolerance mechanism of B. papyrifera. Our findings can provide technical support for producing Se-enriched fodder.
Sexual Mixing by HIV Status and Pre-exposure Prophylaxis Use Among Men Who Have Sex With Men: Addressing Information Bias
Authors: Maloney Kevin M. , Benkeser David , Sullivan Patrick S. , Kelley Colleen , Sanchez Travis , Jenness Samuel M.
Published: July 2022

Background:

Population-level estimates of sexual network mixing for parameterizing prediction models of pre-exposure prophylaxis (PrEP) effectiveness are needed to inform prevention of HIV transmission among men who have sex with men (MSM). Estimates obtained by egocentric sampling are vulnerable to information bias due to incomplete respondent knowledge.

Methods:

We estimated patterns of serosorting and PrEP sorting among MSM in the United States using data from a 2017–2019 egocentric sexual network study. Respondents served as proxies to report the HIV status and PrEP use of recent sexual partners. We contrasted results from a complete-case analysis (unknown HIV and PrEP excluded) versus a bias analysis with respondent-reported data stochastically reclassified to simulate unobserved self-reported data from sexual partners.

Results:

We found strong evidence of preferential partnering across analytical approaches. The bias analysis showed concordance between sexual partners of HIV diagnosis and PrEP use statuses for MSM with diagnosed HIV (39%; 95% simulation interval: 31, 46), MSM who used PrEP (32%; 21, 37), and MSM who did not use PrEP (83%; 79, 87). The fraction of partners with diagnosed HIV was higher among MSM who used PrEP (11%; 9, 14) compared with MSM who did not use PrEP (4%; 3, 5). Comparatively, across all strata of respondents, the complete-case analysis overestimated the fractions of partners with diagnosed HIV or PrEP use.

Conclusions:

We found evidence consistent with HIV and PrEP sorting among MSM, which may decrease the population-level effectiveness of PrEP. Bias analyses can improve mixing estimates for parameterization of transmission models.
Homogeneity in the Instrument-exposure Association and Point Estimation Using Binary Instrumental Variables
Authors: Hartwig Fernando Pires , Wang Linbo , Davey Smith George , Davies Neil Martin
Published: July 2022

Background:

Interpreting instrumental variable results often requires further assumptions in addition to the core assumptions of relevance, independence, and the exclusion restriction.

Methods:

We assess whether instrument-exposure additive homogeneity renders the Wald estimand equal to the average derivative effect (ADE) in the case of a binary instrument and a continuous exposure.

Results:

Instrument-exposure additive homogeneity is insufficient for ADE identification when the instrument is binary, the exposure is continuous, and the effect of the exposure on the outcome is nonlinear on the additive scale. For a binary exposure, the exposure-outcome effect is necessarily additive linear, so the homogeneity condition is sufficient.

Conclusions:

For binary instruments, instrument-exposure additive homogeneity identifies the ADE if the exposure is also binary. Otherwise, additional assumptions (such as additive linearity of the exposure-outcome effect) are required.
Adenomyosis and fertility: does adenomyosis impact fertility and does treatment improve outcomes
Authors: French Hannah M. , Zhang Wenjia , Movilla Peter R. , Isaacson Keith B. , Morris Stephanie N.
Published: July 2022

Purpose of review

Adenomyosis has recently been associated with infertility. Relief of bleeding and pain has been demonstrated with medical and surgical therapy. Less is known about reproductive outcomes after treatment.

Recent findings

Imaging findings during infertility evaluation can be suggestive of adenomyosis without pathologic evaluation. Among women with infertility undergoing assisted reproductive technologies (ART), adenomyosis is associated with lower live birth rates and clinical pregnancy rates. Treatment with gonadotropin releasing hormone (GnRH) modulators prior to frozen embryo transfer may increase the live birth rate and clinical pregnancy rate among women with adenomyosis. Pregnancy has been documented following image-guided adenomyosis ablation; however, the reproductive impact is not well established. Pregnancy following excisional procedures appears to be well tolerated, although may carry a higher risk of uterine rupture compared with pregnancy following myomectomy. It is not clear if ablative therapy or resection increases pregnancy rates.

Adenomyosis is associated with lower embryo implantation rates and ongoing pregnancy rates. Adenomyotic changes in the uterus can be seen by ultrasound and MRI. GnRH modulators may be useful for women with adenomyosis undergoing ART. Additional prospective data is warranted to determine the optimal medical or surgical therapy for women with adenomyosis desiring conception.

Video abstract Supplementary digital content, http://links.lww.com/COOG/A78.
Training for the future
Authors: Ghidei Luwam , Frishman Gary N.
Published: July 2022

Purpose of review

The aim of this study was to review the evolving field of Reproductive Endocrinology and Infertility (REI) and describe the current and future challenges REI fellowship programmes in the United States are facing.

Recent findings

The field of REI continues to rapidly evolve largely due to the tremendous advances within the assisted reproductive technologies (ARTs). Alongside this evolution, there is a lessening emphasis on graduates being proficient in all aspects of REI. Ongoing revisions to the REI fellowship structure reflect these changes in technology and contemporary practice patterns.

REI is a rapidly evolving field and fellowship training is continually adapting to meet the changing landscape of our field.
Radiofrequency ablation methods for uterine sparing fibroid treatment
Authors: Baxter Briana L. , Seaman Sierra J. , Arora Chetna , Kim Jin Hee
Published: July 2022

Purpose of review

This article provides a clinical review of radiofrequency ablation (RFA) for the treatment of uterine leiomyomas.

Recent findings

RFA is an effective and durable treatment for fibroids with sustained improvements in fibroid volume, bleeding, and patient reported outcomes with low reintervention rates. Although fertility data is limited, it is overall positive and may represent a uterine conserving and fertility preserving treatment modality.

RFA is a safe and effective uterine preserving treatment option for symptomatic leiomyomas.