bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Drug Exposure on Resistance Selection Following Artemether‐Lumefantrine Treatment for Malaria in Children With and Without HIV in Uganda
Authors: Kay Katherine , Goodwin Justin , Ehrlich Hanna , Ou Joyce , Freeman Tracey , Wang Kaicheng , Li Fangyong , Wade Martina , French Jonathan , Huang Liusheng , Aweeka Francesca , Mwebaza Norah , Kajubi Richard , Riggs Matthew , Ruiz‐Garcia Ana , Parikh Sunil
Published: October 2022

Artemisinin‐based combination therapies (ACTs) are the primary treatment for malaria. It is essential to characterize the pharmacokinetics (PKs) and pharmacodynamics (PDs) of ACTs in vulnerable populations at risk of suboptimal dosing. We developed a population PK/PD model using data from our previous study of artemether‐lumefantrine in HIV‐uninfected and HIV‐infected children living in a high‐transmission region of Uganda. HIV‐infected children were on efavirenz‐, nevirapine‐, or lopinavir‐ritonavir‐based antiretroviral regimens, with daily trimethoprim‐sulfamethoxazole prophylaxis. We assessed selection for resistance in two key parasite transporters, pfcrt and pfmdr1, over 42‐day follow‐up and incorporated genotyping into a time‐to‐event model to ascertain how resistance genotype in relation to drug exposure impacts recurrence risk. Two hundred seventy‐seven children contributed 364 episodes to the model (186 HIV‐uninfected and 178 HIV‐infected), with recurrent microscopy‐detectable parasitemia detected in 176 episodes by day 42. The final model was a two‐compartment model with first‐order absorption and an estimated age effect on bioavailability. Systemic lumefantrine exposure was highest with lopinavir‐ritonavir, lowest with efavirenz, and equivalent with nevirapine and HIV‐uninfected children. HIV status and lumefantrine concentration were significant factors associated with recurrence risk. Significant selection was demonstrated for pfmdr1 N86 and pfcrt K76 in recurrent infections, with no evidence of selection for pfmdr1 Y184F. Less sensitive parasites were able to tolerate lumefantrine concentrations ~ 3.5‐fold higher than more sensitive parasites. This is the first population PK model of lumefantrine in HIV‐infected children and demonstrates selection for reduced lumefantrine susceptibility, a concern as we confront the threat to ACTs posed by emerging artemisinin resistance in Africa.
RETRACTED: Response of intercropping coffee (Coffea arabica L.) with banana (Musa spp.) on yield, yield components, and quality of coffee
Authors: Tehulie Nuru Seid , Nigatie Taminaw Zewdie
Published: October 2022

The coffee plant (Coffea arabica L.) is thought to have begun as an understory tree species in Ethiopia's northeastern high rain forests. Bananas (Musa spp.) are commonly intercropped with coffee to provide shade as well as food and money. However, the effect of this practice on coffee production is little known, hence the present study was initiated with the objective of evaluating the effect of intercropping coffee with banana on the yield and quality of both crops. The experiment was carried out using mature coffee intercropped with banana (var. Butezua) in different ratios in Kalu district, northeastern Ethiopia between the 2018 and 2020 cropping seasons. It was conducted in a randomized complete block design with three replications of four intercropping ratios (4C:1B, 3C:1B, 2C:1B, and 1C:1B) and two sole cropped plots (sole coffee, C; and sole banana, B). Over years, analysis of variance showed that intercropping of coffee and banana highly significantly (p < .01) influenced yield and growth parameters, such as clean coffee (a coffee free of taints and defects) yield, total plant height, number of main stem nodes, main stem internode length, number and percent of bearing primary branches, number of fruiting nodes per branch, canopy diameter, leaf length, leaf width, and leaf area of coffee trees. Similarly, coffee bean length, bean width, bean thickness, height up to the first primary branch, and number of primary branches were significantly (p < .05) affected by the treatments. In general, the results revealed that among the intercropped treatments, the staggered planting pattern (4C:1B) gave the maximum clean coffee yield (1,357.3 kg ha−1) and fresh banana fruit yield (20,482 kg ha−1) followed by the 3C:1B treatment, which gave (1,346.5 and 21,321 kg ha−1) clean coffee and green banana yields, respectively. In addition, higher mean land equivalent ratios (LER) of 1.78 and 1.61 and maximum net benefits of 316,265.50 and 302,484.00 Ethiopian birr (ETB) ha−1 were obtained from 4C:1B and 3C:1B, respectively. Therefore, it can be concluded that farmers in the Kalu area and similar agro‐ecologies can use these two ratios when practicing coffee–banana intercropping. Further intercropping studies may be required to validate the present results over locations.
Honeycomb‐Type TiO2 Films Toward a High Tolerance to Optical Paths for Perovskite Solar Cells
Authors: Bao Yaqi , Wang Dourong , Hui Wei , Gu Lei , Chao Lingfeng , Song Lin
Published: October 2022

Given the advantages of high power conversion efficiencies (PCEs), antisolvent‐step free production, and suitability for device production in ambient conditions, perovskite solar cells (PSCs) based on ionic‐liquid solvents have attained particular research interest. To further improve device performance, light management could be optimized to increase light harvesting in the perovskite layer. Here, ordered honeycomb‐like TiO2 (Hc‐TiO2) structures with a periodicity of around 450 nm were fabricated through a sacrificial template method. With this photonic crystal structure, the control to light flow and the confinement effect for perovskite growth were achieved simultaneously in the Hc‐TiO2, leading to improved light absorption as well as preferred crystal orientation. Furthermore, a reduced trap‐state density and a well‐aligned energy level induced by the perovskite/pore interlayer facilitated the charge‐carrier extraction from the perovskite layer to electron transport layer. As a result, the structured devices performed better than the planar cells. And the angular dependent J–V sweeps show that the structured device reserved 76 % of its initial short circuit current density (Jsc), whereas the planar cell showed more than a half loss under the incident light of 40°, demonstrating a reduced downward trend in Jsc with the presence of photonic crystal structures. This occurrence also suggests that the structured PSCs in this work have a high tolerance to optical path changes.
Detection of 18‐methyl steroids: Case report on a forensic urine sample and corresponding dietary supplements
Authors: Thieme Detlef , Anielski Patricia , Rzeppa Sebastian , Wolf Clemens A. , Wolber Gerhard , Keiler Annekathrin M.
Published: October 2022

The detection of a putative 18‐methyl‐19‐nortestosterone metabolite in a forensic bodybuilder's urine sample collected as part of a criminal proceeding has triggered a follow‐up investigation. Four different dietary supplements in the possession of the suspect were examined with regard to possible precursor steroids. This led to the detection of the declared ingredient methoxydienone, which was confirmed by both, GC–MSMS and LC‐HRMSMS. As neither 18‐methyl‐testosterone, nor 18‐methyl‐19‐nortestosterone were detectable in the supplements, the possibility that the metabolite originates from methoxydienone was investigated. For this purpose, the metabolic fate of methoxydienone was studied in vitro using human HepG2 cells and in vivo by a single oral administration. While the 18‐methyl‐19‐nortestosterone metabolite was not generated by HepG2 cells incubated with methoxydienone, it was observed in the urine samples collected at 2, 6, 10 and 24 h after methoxydienone administration. Moreover, the potential binding of methoxydienone as ligand to the human androgen receptor was modelled in silico in comparison with 18‐methylnandrolone, for which androgen receptor activation had been shown in an in vitro approach before. In conclusion, we could ascribe the presence of the 18‐methyl‐19‐nortestosterone metabolite in a forensic urine sample to originate from methoxydienone present in dietary supplements. Methoxydienone was observed to slowly degrade by demethylation of the methoxy substituent in liquid solutions. While no compound‐specific intermediates were identified that allowed differentiation from other 18‐methyl steroids, the 18‐methyl‐19‐nortestosterone metabolite proved to be a suitable marker for reliable detection in doping analysis.
BeeDNA: Microfluidic environmental DNA metabarcoding as a tool for connecting plant and pollinator communities
Authors: Harper Lynsey R. , Niemiller Matthew L. , Benito Joseph B. , Paddock Lauren E. , Knittle E. , Molano‐Flores Brenda , Davis Mark A.
Published: October 2022

Pollinators are declining globally, and this loss can reduce plant reproduction, erode critical ecosystem services and resilience, and drive economic losses. Monitoring pollinator biodiversity trends is essential for adaptive conservation and management, but conventional surveys are often costly, time‐consuming, and requires considerable taxonomic expertise. Environmental DNA (eDNA) metabarcoding surveys are booming due to their rapidity, nondestructiveness, and cost efficiency. Microfluidic technology allows multiple primer sets from different markers to be used in eDNA metabarcoding for more comprehensive inventories, minimizing associated primer bias. We evaluated microfluidic eDNA metabarcoding for pollinator community monitoring in both controlled greenhouse and natural field settings. Using a variety of sampling, preservation, and extraction methods, we assessed pollinator communities with a number of markers using microfluidic metabarcoding. In greenhouse experiments, microfluidic eDNA metabarcoding detected the target bumblebee in two of four focal flower species as well as greenhouse insects in all focal flower species. In the field, numerous common regional arthropods, including some directly observed, were detected. Pollinator detection was maximized using whole flower heads preserved in ATL buffer and extracted with a modified Qiagen® DNeasy protocol for amplification with COI primers. eDNA surveillance could enhance pollinator assessment by detecting protected and endangered species and being more applicable to remote, inaccessible locations, whilst reducing survey time, effort, and expense. Microfluidic eDNA metabarcoding requires optimization to address remaining efficacy concerns, but this approach shows potential in revealing complex networks underpinning critical ecosystem functions and services, enabling more accurate assessments of ecosystem resilience.
Development of a hands‐free electrolarynx for obtaining a human‐like voice using the LPC residual wave
Authors: Takeuchi Masaki , Soejima Yutaro , Ahn Jaesol , Lee Kunhak , Takaki Ken , Ifukube Tohru , Yabu Ken‐Ichiro , Takamichi Shinnosuke , Sekino Masaki
Published: October 2022

The conventional electrolarynx (EL) restores the voice of people who have lost their voice, however, its voice sounds like a robot and it occupies user's one hand. Therefore, we developed a hands‐free wearable electrolarynx that improves the voice quality with the LPC residual wave as the vibration sound. Our device was able to reproduce sounds below 500 Hz, which is close to the fundamental frequency, but from 1700 Hz to 4000 Hz, the conventional EL continuously showed a frequency response closer to the spectrum of the user's vocal sound than our device. Thus, the periodic sound of the fundamental frequency band was found to be closer to human speech than individuality or sound quality.
Electrocatalytic Generation of Acyl Radicals and Their Applications
Authors: Zhang Haonan , Liang Sen , Wei Dengchao , Xu Kun , Zeng Chengchu
Published: October 2022

In this review, we highlighted the main achievements in the field of electrocatalytic generation of acyl radicals and their applications. These electrochemical strategies were introduced with an emphasis on the substrate scope, reaction limitation and underlying mechanism. The related reactions were categorized according to the pathways of acyl radical generation, including outer‐sphere electron transfer (ET), inner‐sphere ET, and hydrogen atom transfer (HAT) processes.
Nickel‐Catalyzed Cascade Cyclization‐Negishi Coupling of Redox Active Esters for the Synthesis of Pyrrolidines
Authors: Nieto‐Carmona Juan Carlos , San Román Raúl , Buñuel Elena , Cárdenas Diego J.
Published: October 2022

We have developed a Ni‐catalyzed cascade cyclization/Negishi‐coupling reaction for the formation of pyrrolidines and pyrrolidinones starting from N‐protected allylamines and acrylamides which contain a redox active ester group. The reaction provides two C−C bonds in a single operation and takes place with both alkylzinc and arylzinc bromides as nucleophiles. Activation of RAE by low valent Ni complexes involving a radical pathway followed by a fast cyclization of intermediate carbon radicals is proposed.
Copper(I)‐Catalyzed Regioselective Tandem Cyanoalkylative Cyclization of 1,5‐Dienes with Cyclobutanone Oxime Esters
Authors: Wang Panpan , Leng Yuting , Wu Yangjie
Published: October 2022

An effective strategy for construction of 1,5‐dihydro‐2H‐pyrrol‐2‐one scaffolds by a cascade of 1,5‐dienes with cyclobutanone oxime esters was developed. The reaction proceeded through radical addition, 5‐endo cyclization, and subsequent deprotonation, in which two new C−C bonds were formed. This protocol features excellent regioselectivity and a low‐cost catalyst, as well as broad substrate scope, which are expected to promote its potential applications in pharmacy and synthetic chemistry.
Application of Hilbert instantaneous spectrum on improved bolt anchoring quality detection
Authors: Li Chen , Gao Guozhong , Wang Yunsheng
Published: October 2022

The nondestructive testing technology for bolt anchoring quality based on the acoustic reflection method is developing rapidly. Hilbert transform instantaneous spectrum is frequently used. However, due to the existence of the folding phenomenon in the instantaneous phase, the accurate identification of reflected signal and the effective calculation of the anchorage compactness remain a challenge. The instantaneous frequency curve of the bolt signal is used to overcome the phase folding problem. The instantaneous frequency curve of the signal can help accurately identify the reflected signal from the bolt bottom and the position of the defect, thus accurately calculate the length of the bolt and the position of the defect. According to the analysis of the instantaneous amplitude curve of the signal, the formula for computing the bolt anchorage compactness is derived based on the correlation between the attenuation amplitude ratio of the reflected signal and the bolt anchoring quality. Research results show that difficult problems such as bolt reflection signal identification and anchorage compactness calculation are both effectively solved. The model simulation analyzes and field application examples verify the effectiveness and practicability of the methodology, which provides a robust way for the nondestructive testing of the bolt anchoring quality.
Lithium Difluoro(Oxalate)Borate‐Induced Interphase for High‐Voltage LiFe0.15Co0.85PO4@C Cathode by Solid‐State Synthesis
Authors: Sreedeep Sreekumar , Natarajan Subramanian , Lee Yun-Sung , Aravindan Vanchiappan
Published: October 2022

Herein, the effect of lithium difluoro(oxalate)borate (LiDFOB) as an electrolyte additive on the electrochemical performance of LiFe0.15Co0.85PO4@C (LFCP@C) cathode, synthesized by a scalable solid‐state synthesis method is reported. Galvanostatic studies revealed better electrochemical performance among the LFCP@C (LiDFOB: 0.5–2 wt%) in a half‐cell assembly compared to the LiFe0.15Co0.85PO4 in the absence of LiDFOB. Also, among the various concentrations of LiDFOB, the LFCP@C (LiDFOB—1.5 wt%) and LFCP@C (LiDFOB—2 wt%) are optimized as suitable candidates for further electrochemical studies owing to the high discharge capacities of 116 and 118 mAh g−1. In addition, the electrochemical impedance studies (EIS) exhibited an increase in the charge–transfer resistance (R
ct) as the amount of LiDFOB was increased, whereas a lower R
ct value is observed in the absence of additive. In addition, the diffusion coefficient calculation is calculated using the EIS data, which shows a diffusion coefficient in the order of ≈10−13 cm2 s−1. However, as the amount of LiDFOB is increased from 0 to 2 wt%, a decrease in the diffusion coefficient is observed owing to the formation of a stable and thicker passivation layer.
Channel synchronization based on deep learning
Authors: Wei Peng , Lu Ruimin , Ye Ganhua , Xie Shijun , Wang Ruidong
Published: October 2022

Aiming at the difficulty of the deep neural network (DNN) adapting to channel changes in communication systems, a channel synchronization deep neural network (CSDNN) based on deep learning (DL) is designed for realizing carrier synchronization, bit timing synchronization, and automatic gain control (AGC). By introducing a frequency‐domain cyclic convolution (FDCC) layer, the network transformed the time‐domain triangle activation into frequency domain linear activation taking FFT and IFFT matrixes as the activation function, solved the reverse gradient transmission‐blocking problems in training the time‐domain carrier synchronization neural network, effectively overcome the FFT inherent “fence” effect, and accurately compensated carrier frequency offset; By introducing a time‐domain cyclic convolution (TDCC) layer and the special frame structure design containing repetitive training sequence, the network training was completed to realize bit timing synchronization under the condition of the uncertain corresponding relationship between training data and labels. Combining phase inverse rotation dense (PIRD) layer, the network can be trained with very little training data to complete fast carrier synchronization and timing synchronization, at the same time adjust the received signal gain and suppress the jamming, which makes it is possible to train the channel synchronization deep neural network online under jamming environment, and provide a feasible way of realizing the intelligent communication system.
Education disrupted: Students beginning college during the COVID‐19 pandemic
Authors: Kinzie Jillian , Cole James
Published: October 2022

In the second year of the COVID‐19 pandemic, students entering college in fall 2021 had an unprecedented culmination to high school and transition to college. This chapter explores the experience of entering college students following these unprecedented circumstances, examining high school disruptions, including changes in the learning environment and its relationship to instructional mode preferences in college, and documenting students’ sense of optimism for college, their mental and emotional health, and perceptions of academic difficulty. Results show that the educational impact of the pandemic was not uniform across student groups and will remain an important factor in these students’ educational journey.
Methods to study adult hippocampal neurogenesis in humans and across the phylogeny
Authors: Terreros‐Roncal Julia , Flor‐García Miguel , Moreno‐Jiménez Elena P. , Rodríguez‐Moreno Carla B. , Márquez‐Valadez Berenice , Gallardo‐Caballero Marta , Rábano Alberto , Llorens‐Martín María
Published: October 2022

The hippocampus hosts the continuous addition of new neurons throughout life—a phenomenon named adult hippocampal neurogenesis (AHN). Here we revisit the occurrence of AHN in more than 110 mammalian species, including humans, and discuss the further validation of these data by single‐cell RNAseq and other alternative techniques. In this regard, our recent studies have addressed the long‐standing controversy in the field, namely whether cells positive for AHN markers are present in the adult human dentate gyrus (DG). Here we review how we developed a tightly controlled methodology, based on the use of high‐quality brain samples (characterized by short postmortem delays and ≤24 h of fixation in freshly prepared 4% paraformaldehyde), to address human AHN. We review that the detection of AHN markers in samples fixed for 24 h required mild antigen retrieval and chemical elimination of autofluorescence. However, these steps were not necessary for samples subjected to shorter fixation periods. Moreover, the detection of labile epitopes (such as Nestin) in the human hippocampus required the use of mild detergents. The application of this strictly controlled methodology allowed reconstruction of the entire AHN process, thus revealing the presence of neural stem cells, proliferative progenitors, neuroblasts, and immature neurons at distinct stages of differentiation in the human DG. The data reviewed here demonstrate that methodology is of utmost importance when studying AHN by means of distinct techniques across the phylogenetic scale. In this regard, we summarize the major findings made by our group that emphasize that overlooking fundamental technical principles might have consequences for any given research field.
Relative sensitivity value (RSV): A metric for measuring input parameter influence in life cycle assessment modeling
Authors: Bhatt Akul , Abbassi Bassim
Published: October 2022

Life cycle assessment (LCA) is a commonly used tool to quantify life cycle environmental footprints of products. Uncertainty in LCA modeling, particularly from uncertainty in production practices (represented through input parameter arguments), can lead to incorrect conclusions and hamper decision-making. Characterization of uncertainty through stochastic means and sensitivity analysis is utilized in a small fraction of LCA case studies, and the majority of studies default to scenario analysis due to its lower barrier to implementation and its results are easier to interpret. In this article, we introduce a sensitivity metric, relative sensitivity value (RSV), which allows LCA practitioners to gauge the relative influence of production practices on life cycle impacts in multiple phases and impact categories. Relative sensitivity value bridges the gap between scenario analysis and global sensitivity analysis, and it allows an LCA practitioner to provide an easy-to-interpret metric for quantifying the degree to which incremental changes in production practices influences the life cycle environmental footprint. We present the methodology used to calculate RSV and provide programming code, which can be readily used by an LCA practitioner to calculate RSV for their LCA model. We demonstrate the usage of RSV through a livestock husbandry LCA case study, in which we show how RSV results may be presented and interpreted, and how conclusions regarding production practices may be drawn. Integr Environ Assess Manag 2023;19:547–555. © 2022 SETAC
Enantioselective Synthesis of [5]Helicenes Containing Two Additional Chiral Axes
Authors: Zhang Jianwei , Simon Martin , Golz Christopher , Alcarazo Manuel
Published: October 2022

A Au‐catalyzed protocol for the enantioselective synthesis of molecular architectures containing an internal [5]helicene and two peripherical axial stereogenic elements is described. While the diasteroselectivity of the double alkyne hydroarylation sequence is not optimal, and mixtures that contain similar amounts of two of the four possible diasteromeric products are obtained (one C2 and one non‐symmetric), the assembly of the C2‐symmetric isomer often occurs with high enantioselectivity (up to 98 % ee). The absolute configurations of the products obtained were determined by X‐ray crystallography. Studies on the thermal racemization of the internal [5]helicene moiety in the C2‐symmetric isomers determined the half‐life of this element to be approximately 3 h at 50 °C.
Recurrent multiple liver metastases of clear cell renal cell carcinoma with a significant response to sunitinib after nivolumab treatment
Authors: Tada Kouki , Daizumoto Kei , Takahashi Masayuki , Uehara Hisanori , Tsuda Megumi , Kusuhara Yoshito , Fukawa Tomoya , Yamamoto Yasuyo , Yamaguchi Kunihisa , Kanayama Hiro‐omi
Published: October 2022

Introduction

A case of multiple liver metastases of clear cell RCC with a significant response to sunitinib as the fifth line after nivolumab is reported.

Case presentation

The patient was a 65‐year‐old man who underwent open nephrectomy for RCC. After the nephrectomy, he had recurrences several times, and metastasectomy had been performed for each recurrence. At 13 years after the nephrectomy, multiple liver, and lung metastases appeared. The treatment was switched to axitinib, followed by cabozantinib, then nivolumab. The best response was PR, SD, and PD for these three drugs, and treatment duration was 14, 3, and 3 months, respectively. As the fifth line, sunitinib was administered, with significant shrinkage of the multiple liver metastases, and PR has been maintained for 34 months.

Conclusion

Sunitinib after an IO‐drug showed a significant effect in spite of only slight efficacy with other VEGFR‐TKIs, which may have occurred through the alteration of the immunological microenvironment.
IntramuscularEMGclassifier for detecting myopathy and neuropathy
Authors: Jose Shobha , Selvaraj Thomas George , Samuel Kenneth , Philip Jobin T. , Nanjappan Jothiraj Sairamya , Muthu Swamy Pandian Subathra , Handiru Vikram Shenoy , Suviseshamuthu Easter S.
Published: October 2022

This article presents an automatic diagnostic system to classify intramuscular electromyography (iEMG) signals, thereby detecting neuromuscular disorders. To this end, we tailored the center symmetric local binary pattern (CSLBP) to analyze one‐dimensional (‐D) signals. In this approach, the ‐D CSLBP feature extracted from a decimated iEMG signal is fed to a combination of classifiers, which in turn assigns a set of labels to the signal, and ultimately the signal category is determined by the Boyer‐Moore majority voting (BMMV) algorithm. The proposed framework was investigated with a benchmark iEMG dataset that contains signals recorded from three different muscles:biceps brachii(BB),deltoideus(DE), andvastus medialis(VM). In a repeated ‐fold cross‐validation, CSLBP‐Combined‐Classifiers‐BMMV (CSLBP‐CC‐BMMV) achieved an average classification accuracy of %, %, and % for the iEMG signals recorded from BB, DE, and VM muscle, respectively. Interestingly, the performance of CSLBP‐CC‐BMMV surpassed the other published approaches and ensemble learning methods that are akin to our scheme in terms of classification accuracy and computational time.
Polarization clustering of biological structures with Mueller matrix parameters
Authors: Chen Yongtai , Chu Jinkui , Lin Fanlu , Jiang Bing , Liu Yadong , Huang Bo , Zhang Ran , Xin Benda , Ding Xiaohan
Published: October 2022

Mueller matrix imaging polarimetry (MMIP) is a promising technique for the characterization of biological tissues, including the classification of microstructures in pathological diagnosis. To expand the parameter space of Mueller matrix parameters, we propose new vector parameters (VPs) according to the Mueller matrix polar decomposition method. We measure invasive bladder cancer (IBC) with extensive necrosis and high‐grade ductal carcinoma in situ (DCIS) with MMIP, and the regions of cancer cells and fibrotic stroma are classified with the VPs. Then the proposed and existing VPs are mapped on the Poincaré sphere with 3D visualization, and an indicator of spatial feature is defined based on the minimum enclosing sphere to evaluate the classification capability of the VPs. For both IBC and DCIS, the results show that the proposed VPs exhibit evident contrast between the regions of cancer cells and fibrotic stroma. This study broadens the fundamental Mueller matrix parameters and helps to improve the characterization ability of the MMIP technique.
A discourse analysis of cultural humility within counseling dyads
Authors: Zhu Peitao , Isawi Dana T. , Luke Melissa M.
Published: October 2022

A growing body of empirical literature has substantiated that cultural humility (CH) contributes meaningfully to a variety of therapeutic processes and outcomes. However, no study has concretely described how CH is linguistically and discursively enacted within therapeutic exchanges. Using interactional sociolinguistic discourse analysis, we explored the sociolinguistic strategies along with three dimensions of CH: (a) cultural teachability, (b) lack of cultural arrogance, and (c) relational orientation. Participants included six pairs of cross‐racial counseling dyads. Our analyses of the session and follow‐up interview transcripts yielded a range of sociolinguistic strategies (i.e., positioning, use of reinforcement, repetition, and use of pronouns) corresponding to the CH dimensions. We discuss clinical, research, and training implications.
Race, masks, residency and concern regarding COVID‐19 transmission
Authors: Azhar Sameena , Rahman Rahbel , Wernick Laura J. , Tripathi Saumya , Cohen Margaret , Maschi Tina
Published: October 2022

To explore sociodemographic predictors for concern regarding COVID‐19 transmission and how these factors interact with the identities of others, we conducted a web‐based survey where we asked 568 respondents in the United States to indicate their level of COVID‐19 concern in response to a series of images with short vignettes of masked and unmasked individuals of different racial/ethnic backgrounds. Using a linear mixed effects model, we found that regardless of the race of the image being presented in the vignette, concern regarding COVID‐19 transmission was associated with respondents' older age (b = 0.029, p < 0.001), residing in NYC (b = 0.556, p = 0.009), being heterosexual (b = 1.075, p < 0.001), having higher levels of education, that is, completion of a Bachelor's degree (b = 1.10, p = 0.033) or graduate degree (b = 1.78, p < 0.001), and the person in the vignette being unmasked (b = 0.822, p < 0.001). Asian respondents were more likely than White respondents to be concerned regarding COVID‐19. Individuals who self‐reported themselves to be at high risk for COVID‐19 were more likely to be concerned about COVID‐19 over those who considered themselves to be low risk. These findings highlight the importance of acknowledging interactions between race, mask status, and residency in predicting COVID‐19 concern.
The role of ferroptosis in the development of acute and chronic kidney diseases
Authors: Zhou Yijun , Zhang Junlan , Guan Qingyan , Tao Xun , Wang Jinling , Li Wentong
Published: October 2022

Ferroptosis, a novel form of regulated cell death, is characterized by imbalance of intracellular iron and redox systems, resulting from overgeneration of toxic lipid peroxidation products. In recent years, the verified crucial role of ferroptosis has been widely concerned in rudimentary pathogenesis and development of various acute and chronic kidney disease (CKD), comprehending the potential patterns of cell death can afford more reliable bases and principles for treatment and prevention of renal disease. In this review, the regulatory mechanisms of ferroptosis were introduced and the important roles of ferroptosis in diverse renal diseases such as acute kidney injury, CKD, and renal fibrosis were outlined to illuminate the potential of restraining ferroptosis in treatment and prevention of kidney disease.
Pyruvate dehydrogenase kinase 4 promotes ubiquitin–proteasome system‐dependent muscle atrophy
Authors: Sinam Ibotombi Singh , Chanda Dipanjan , Thoudam Themis , Kim Min‐Ji , Kim Byung‐Gyu , Kang Hyeon‐Ji , Lee Jung Yi , Baek Seung‐Hoon , Kim Shin‐Yoon , Shim Bum Jin , Ryu Dongryeol , Jeon Jae‐Han , Lee In‐Kyu
Published: October 2022

Background

Muscle atrophy, leading to muscular dysfunction and weakness, is an adverse outcome of sustained period of glucocorticoids usage. However, the molecular mechanism underlying this detrimental condition is currently unclear. Pyruvate dehydrogenase kinase 4 (PDK4), a central regulator of cellular energy metabolism, is highly expressed in skeletal muscle and has been implicated in the pathogenesis of several diseases. The current study was designed to investigated and delineate the role of PDK4 in the context of muscle atrophy, which could be identified as a potential therapeutic avenue to protect against dexamethasone‐induced muscle wasting.

Methods

The dexamethasone‐induced muscle atrophy in C2C12 myotubes was evaluated at the molecular level by expression of key genes and proteins involved in myogenesis, using immunoblotting and qPCR analyses. Muscle dysfunction was studied in vivo in wild‐type and PDK4 knockout mice treated with dexamethasone (25 mg/kg body weight, i.p., 10 days). Body weight, grip strength, muscle weight and muscle histology were assessed. The expression of myogenesis markers were analysed using qPCR, immunoblotting and immunoprecipitation. The study was extended to in vitro human skeletal muscle atrophy analysis.

Results

Knockdown of PDK4 was found to prevent glucocorticoid‐induced muscle atrophy and dysfunction in C2C12 myotubes, which was indicated by induction of myogenin (0.3271 ± 0.102 vs 2.163 ± 0.192, ****P < 0.0001) and myosin heavy chain (0.3901 ± 0.047 vs. 0.7222 ± 0.082, **P < 0.01) protein levels and reduction of muscle atrophy F‐box (10.77 ± 2.674 vs. 1.518 ± 0.172, **P < 0.01) expression. In dexamethasone‐induced muscle atrophy model, mice with genetic ablation of PDK4 revealed increased muscle strength (162.1 ± 22.75 vs. 200.1 ± 37.09 g, ***P < 0.001) and muscle fibres (54.20 ± 11.85% vs. 84.07 ± 28.41%, ****P < 0.0001). To explore the mechanism, we performed coimmunoprecipitation and liquid chromatography‐mass spectrometry analysis and found that myogenin is novel substrate of PDK4. PDK4 phosphorylates myogenin at S43/T57 amino acid residues, which facilitates the recruitment of muscle atrophy F‐box to myogenin and leads to its subsequent ubiquitination and degradation. Finally, overexpression of non‐phosphorylatable myogenin mutant using intramuscular injection prevented dexamethasone‐induced muscle atrophy and preserved muscle fibres.

Conclusions

We have demonstrated that PDK4 mediates dexamethasone‐induced skeletal muscle atrophy. Mechanistically, PDK4 phosphorylates and degrades myogenin via recruitment of E3 ubiquitin ligase, muscle atrophy F‐box. Rescue of muscle regeneration by genetic ablation of PDK4 or overexpression of non‐phosphorylatable myogenin mutant indicates PDK4 as an amenable therapeutic target in muscle atrophy.
The (t−1) $(t-1)$‐chromatic Ramsey number for paths
Authors: Bucić Matija , Khamseh Amir
Published: October 2022

The following relaxation of the classical problem of determining the Ramsey number of a fixed graph has first been proposed by Erdős, Hajnal and Rado over 50 years ago. Given a graph and an integer determine the minimum number such that in any ‐coloured complete graph on vertices there is a copy of using only edges of some colours. We determine the answer precisely when is a path.
Comprehensive data of 4502 patients newly diagnosed with colorectal liver metastasis between 2015 and 2017, and prognostic data of 2427 patients newly diagnosed with colorectal liver metastasis in 2013 and 2014: Third report of a nationwide survey in Japan
Authors: Sakamoto Katsunori , Beppu Toru , Honda Goro , Kotake Kenjiro , Yamamoto Masakazu , Takahashi Keiichi , Endo Itaru , Hasegawa Kiyoshi , Itabashi Michio , Hashiguchi Yojiro , Kotera Yoshihito , Kobayashi Shin , Yamaguchi Tatsuro , Natsume Soichiro , Tabuchi Ken , Kobayashi Hirotoshi , Yamaguchi Kensei , Tani Kimitaka , Morita Satoshi , Miyazaki Masaru , Sugihara Kenichi
Published: October 2022

To improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery. The aim of the study was to evaluate transition in the characteristics and treatment strategy in CRLM patients and analyze prognostic factors using large‐scale data. The present study summarizes the data of patients newly diagnosed between 2015 and 2017 and presents prognostic data of patients newly diagnosed in 2013 and 2014. Survival curves were generated by the Kaplan–Meier method and compared by log‐rank test. Multivariate analyses were carried out using Cox proportional hazard modeling. The data of 4502 patients newly diagnosed with CRLM between 2015 and 2017 and the prognostic data of 2427 patients diagnosed in 2013 and 2014 are included. Regarding the 2013 and 2014 prognostic data, the 5‐year overall survival (OS) rates of patients who underwent hepatectomy alone was 59.8%. Multivariate analyses identified age at diagnosis of CRLM ≥70 years, concomitant extrahepatic metastasis at diagnosis of CRLM, tumor depth of primary lesion ≥subserosa/pericolic or perirectal tissue, mutant KRAS status, number of CRLM ≥5, maximum diameter of CRLM >5 cm, and surgical curability R1/R2 as independent predictors of OS. Analysis of the latest nationwide database of patients diagnosed with CRLM revealed changes in patients and oncological characteristics, a transition in treatment strategy, and different independent prognosticators to those reported previously.
Pyridazinones: A versatile scaffold in the development of potential target‐based novel anticancer agents
Authors: Singh Jyoti , Kumar Vipan , Silakari Pragati , Kumar Sandeep
Published: October 2022

Pyridazinones are important nitrogen‐rich heterocyclic core that has been driving the substantial medicinal interest due to their wide range of biological activities. This privileged scaffold forms a central core in numerous potent compounds, which results in the development of novel anticancer drugs with fruitful biological activities. The current review article summarizes the progressive development of novel pyridazinone derivatives that are targets for numerous receptors such as C‐met kinase inhibitors, PARP inhibitors, Tubulin polymerization inhibitors, Dihydro folate reductase inhibitors, B‐Raf inhibitors, Bruton tyrosine kinase inhibitors, FER tyrosine kinase inhibitors, and fibroblast growth factors receptors. It features the various simple techniques for the synthesis of pyridazinones and also highlights the mechanistic insights into the anticancer properties of pyridazinone derivatives.
Making the Case for Joint Decision‐Making in Future Multipurpose Prevention Technology (MPT) Choice: Qualitative Findings on MPT Attribute Preferences from the CUPID Study (MTN‐045)
Authors: Bhushan Nivedita L. , Musara Petina , Hartmann Miriam , Stoner Marie C. D. , Shah Shweta R. , Nabukeera Josephine , Rukundo Ivan , Mutero Prisca , Lewis Megan A. , Piper Jeanna , Shapley‐Quinn Mary Kate , Etima Juliane , Minnis Alexandra M.
Published: October 2022

Introduction

Young women in sub‐Saharan Africa account for two‐thirds of all new HIV infections and face high rates of unintended pregnancy. Multipurpose prevention technologies (MPTs) are promising products under development that are designed to simultaneously prevent HIV and unintended pregnancy. Since MPTs will be used in the context of sexual relationships, ensuring acceptability and use requires understanding the role of male partners in MPT use decision‐making.

Methods

This paper draws on qualitative data from 39 couples enrolled in the Microbicide Trials Network (MTN) 045 study, conducted in 2019–2020. Partners completed a discrete choice experiment (DCE), first separately and then jointly, to measure preferences for future MPT attributes and then completed a qualitative interview. We also draw on quantitative data from interviewer observation about who dominated the decision‐making process during the joint DCE. Content analysis was used to examine (1) how couples made decisions on existing non‐MPT HIV and pregnancy prevention products; (2) how couples made decisions on future ideal‐MPT product during the DCE; and (3) how these decision‐making processes varied by decision‐making dominance (10 male, 10 female and 19 equal) and interview type (19 joint and 20 separate).

Results

Existing non‐MPT product decisions focused on trust between partners and product attributes, while future ideal‐MPT product decisions exclusively focused on product attributes. Across existing and future products, preferences for product attributes varied by gender. Male partners were most concerned with limiting side effects impacting sexual pleasure, female partners were most concerned with limiting side effects causing physical symptoms and both were concerned with the return to fertility. Across all dominance and interview types, couples reported making decisions together and female partners were often able to negotiate with male partners for their preferred product or set of product attributes.

Conclusions

Research activities in this study provided an opportunity for couples to openly present their product attribute preferences to their partner, learn about their partner's attribute preferences, negotiate for their ideal set of attributes and ultimately choose attributes that benefited the couple without disempowering the female partner. Future research should focus on the utility of couple‐based decision‐making aids or similar tools for facilitating joint MPT decision‐making.
Systematic analysis to identify novel disease indications and plausible potential chemical leads of glutamate ionotropic receptorNMDAtype subunit 1,GRIN1
Authors: Bhardwaj Tulika , Ahmad Irshad , Somvanshi Pallavi
Published: October 2022

Schizophrenia is a mental illness affecting the normal lifestyle of adults and early adolescents incurring major symptoms as jumbled speech, involvement in everyday activities eventually got reduced, patients always struggle with attention and memory, reason being both the genetic and environmental factors responsible for altered brain chemistry and structure, resulting in schizophrenia and associated orphan diseases. The network biology describes the interactions among genes/proteins encoding molecular mechanisms of biological processes, development, and diseases. Besides, all the molecular networks, protein‐protein Interaction Networks have been significant in distinguishing the pathogenesis of diseases and thereby drug discovery. The present meta‐analysis prioritizes novel disease indications viz. rare and orphan diseases associated with target Glutamate Ionotropic Receptor NMDA Type Subunit 1, GRIN1 using text mining knowledge‐based tools. Furthermore, ZINC database was virtually screened, and binding conformation of selected compounds was performed and resulted in the identification of Narciclasine (ZINC04097652) and Alvespimycin (ZINC73138787) as potential inhibitors. Furthermore, docked complexes were subjected to MD simulation studies which suggests that the identified leads could be a better potential drug to recuperate schizophrenia.
Nomogram Estimating Vessels Encapsulating Tumor Clusters in Hepatocellular Carcinoma From Preoperative Gadoxetate Disodium‐Enhanced MRI
Authors: Chen Fang‐Ming , Du Mingzhan , Qi Xiumin , Bian Linjie , Wu Danping , Zhang Shuang‐Lin , Wang Jitao , Zhou Yongping , Zhu Xiaoli
Published: October 2022

Background

Vessels encapsulating tumor clusters (VETC) pattern is a novel microvascular pattern associated with poor outcomes of hepatocellular carcinoma (HCC). Preoperative estimation of VETC has potential to improve treatment decisions.

Purpose

To develop and validate a nomogram based on gadoxetate disodium‐enhanced MRI for estimating VETC in HCC and to evaluate whether the estimations are associated with recurrence after hepatic resection.

Study Type

Retrospective.

Population

A total of 320 patients with HCC and histopathologic VETC pattern assessment from three centers (development cohort:validation cohort = 173:147).

Field Strength/Sequence

A3.0  T/turbo spin‐echo T2‐weighted, spin‐echo echo‐planar diffusion‐weighted, and 3D T1‐weighted gradient‐echo sequences.

Assessment

A set of previously reported VETC‐ and/or prognosis‐correlated qualitative and quantitative imaging features were assessed. Clinical and imaging variables were compared based on histopathologic VETC status to investigate factors indicating VETC pattern. A regression‐based nomogram was then constructed using the significant factors for VETC pattern. The nomogram‐estimated VETC stratification was assessed for its association with recurrence.

Statistical Tests

Fisher exact test, t‐test or Mann–Whitney test, logistic regression analyses, Harrell's concordance index (C‐index), nomogram, Kaplan–Meier curves and log‐rank tests. P value < 0.05 was considered statistically significant.

Results

Pathological VETC pattern presence was identified in 156 patients (development cohort:validation cohort = 83:73). Tumor size, presence of heterogeneous enhancement with septations or with irregular ring‐like structures, and necrosis were significant factors for estimating VETC pattern. The nomogram incorporating these indicators showed good discrimination with a C‐index of 0.870 (development cohort) and 0.862 (validation cohort). Significant differences in recurrence rates between the nomogram‐estimated high‐risk VETC group and low‐risk VETC group were found (2‐year recurrence rates, 50.7% vs. 30.3% and 49.6% vs. 31.8% in the development and validation cohorts, respectively).

Data Conclusion

The nomogram integrating gadoxetate disodium‐enhanced MRI features was associated with VETC pattern preoperatively and with postoperative recurrence in patients with HCC.

Evidence Level

4

Technical Efficacy

Stage 2
Preoperative Assessment of MRI‐Invisible Early‐Stage Endometrial Cancer With MRI‐Based Radiomics Analysis
Authors: Jiang Xiaoting , Song Jiacheng , Zhang Aining , Cheng Wenjun , Duan Shaofeng , Liu Xisheng , Chen Ting
Published: October 2022

Background

Radiomics‐based analyses have demonstrated impact on studies of endometrial cancer (EC). However, there have been no radiomics studies investigating preoperative assessment of MRI‐invisible EC to date.

Purpose

To develop and validate radiomics models based on sagittal T2‐weighted images (T2WI) and T1‐weighted contrast‐enhanced images (T1CE) for the preoperative assessment of MRI‐invisible early‐stage EC and myometrial invasion (MI).

Study Type

Retrospective.

Population

One hundred fifty‐eight consecutive patients (mean age 50.7 years) with MRI‐invisible endometrial lesions were enrolled from June 2016 to March 2022 and randomly divided into the training (n = 110) and validation cohort (n = 48) using a ratio of 7:3.

Field Strength/Sequence

3‐T, T2WI, and T1CE sequences, turbo spin echo.

Assessment

Two radiologists performed image segmentation and extracted features. Endometrial lesions were histopathologically classified as benign, dysplasia, and EC with or without MI. In the training cohort, 28 and 20 radiomics features were selected to build Model 1 and Model 2, respectively, generating rad‐score 1 (RS1) and rad‐score 2 (RS2) for evaluating MRI‐invisible EC and MI.

Statistical Tests

The least absolute shrinkage and selection operator logistic regression method was used to select radiomics features. Mann–Whitney U tests and Chi‐square test were used to analyze continuous and categorical variables. Receiver operating characteristic curve (ROC) and decision curve analysis were used for performance evaluation. The area under the ROC curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were calculated. A P‐value <0.05 was considered statistically significant.

Results

Model 1 had good performance for preoperative detecting of MRI‐invisible early‐stage EC in the training and validation cohorts (AUC: 0.873 and 0.918). In addition, Model 2 had good performance in assessment of MI of MRI‐invisible endometrial lesions in the training and validation cohorts (AUC: 0.854 and 0.834).

Data Conclusion

MRI‐based radiomics models may provide good performance for detecting MRI‐invisible EC and MI.

Evidence Level

3

Technical Efficacy

Stage 2