bluuebunny/crossref_metadata_2025 huggingface dataset:
OPTIMAL: An OPTimized Imaging Mass cytometry AnaLysis framework for benchmarking segmentation and data exploration
Authors: Hunter Bethany , Nicorescu Ioana , Foster Emma , McDonald David , Hulme Gillian , Fuller Andrew , Thomson Amanda , Goldsborough Thibaut , Hilkens Catharien M. U. , Majo Joaquim , Milross Luke , Fisher Andrew , Bankhead Peter , Wills John , Rees Paul , Filby Andrew , Merces George
Published: September 2023

Analysis of imaging mass cytometry (IMC) data and other low‐resolution multiplexed tissue imaging technologies is often confounded by poor single‐cell segmentation and suboptimal approaches for data visualization and exploration. This can lead to inaccurate identification of cell phenotypes, states, or spatial relationships compared to reference data from single‐cell suspension technologies. To this end we have developed the “OPTimized Imaging Mass cytometry AnaLysis (OPTIMAL)” framework to benchmark any approaches for cell segmentation, parameter transformation, batch effect correction, data visualization/clustering, and spatial neighborhood analysis. Using a panel of 27 metal‐tagged antibodies recognizing well‐characterized phenotypic and functional markers to stain the same Formalin‐Fixed Paraffin Embedded (FFPE) human tonsil sample tissue microarray over 12 temporally distinct batches we tested several cell segmentation models, a range of different arcsinh cofactor parameter transformation values, 5 different dimensionality reduction algorithms, and 2 clustering methods. Finally, we assessed the optimal approach for performing neighborhood analysis. We found that single‐cell segmentation was improved by the use of an Ilastik‐derived probability map but that issues with poor segmentation were only really evident after clustering and cell type/state identification and not always evident when using “classical” bivariate data display techniques. The optimal arcsinh cofactor for parameter transformation was 1 as it maximized the statistical separation between negative and positive signal distributions and a simple Z‐score normalization step after arcsinh transformation eliminated batch effects. Of the five different dimensionality reduction approaches tested, PacMap gave the best data structure with FLOWSOM clustering out‐performing phenograph in terms of cell type identification. We also found that neighborhood analysis was influenced by the method used for finding neighboring cells with a “disc” pixel expansion outperforming a “bounding box” approach combined with the need for filtering objects based on size and image‐edge location. Importantly, OPTIMAL can be used to assess and integrate with any existing approach to IMC data analysis and, as it creates .FCS files from the segmentation output and allows for single‐cell exploration to be conducted using a wide variety of accessible software and algorithms familiar to conventional flow cytometrists.
Asymmetric Synthesis of Pantolactone: Recent Advances
Authors: Du Zhi‐Hong , Lv Xiao‐Xiong , Liu Ning , Chen Fei , Yuan Meng , Da Chao‐Shan
Published: September 2023

(R)‐Pantolactone, an intermediate in the syntheses of Vitamin B5 and coenzyme A, is an important chiral molecule often used as a food additive, chiral auxiliary, and chiral starting material for organic transformations. Enantioenriched pantolactones are predominantly produced by biological fermentation and chemical synthesis approaches. Herein, we present a review of recent developments in the asymmetric synthesis of pantolactone through different methods, and systematically summarize the characteristics and advantageous features of these strategies. Among the strategies discussed herein, the direct asymmetric catalysis of glyoxylate and isobutyraldehyde with small organocatalyst molecules has attracted growing attention owing to its good step‐economy, commercially available starting materials, absence of toxic reagents, mild reaction conditions, convenient operation, and low catalyst loading. These characteristics render the direct asymmetric route to pantolactone a particularly attractive procedure. This review provides valuable guidance for the design and synthesis of enantioenriched pantolactone and its analogs.
Bilateral ictal EEG is associated with better memory outcome after hippocampal sclerosis surgery
Authors: Castro‐Lima Humberto , Passarelli Valmir , Ribeiro Elyse S , Adda Carla C , Preturlon‐Santos Ana Paula P , Jorge Carmen L , Valério Rosa , Tzu Wen Hung , Boa‐Sorte Ney , Pipek Leonardo Zumerkorn , Castro Luiz Henrique M
Published: September 2023

Objective

To compare memory outcomes after surgery for unilateral hippocampal sclerosis (HS)‐associated epilepsy in patients with unilateral and bilateral ictal electrographic involvement.

Methods

We prospectively evaluated HS patients, aged 18‐55 years and IQ ≥70. Left (L) and right (R) surgical groups underwent noninvasive video‐EEG monitoring and Wada test. We classified patients as Ipsilateral if ictal EEG was restricted to the HS side, or Bilateral, if at least one seizure onset occurred contralaterally to the HS, or if ictal discharge evolved to the opposite temporal region. Patients who declined surgery served as controls. Memory was evaluated on two occasions with Rey Auditory‐Verbal Learning Test and Rey Visual‐Design Learning Test. Baseline neuropsychological test scores were compared between groups. Pre‐ and postoperative scores were compared within each group. Reliable change index Z‐scores (RCI) were obtained using controls as references, and compared between surgical groups.

Results

We evaluated 64 patients. Patients were classified as: L‐Ipsilateral (9), L‐Bilateral (15), L‐Control (9), R‐Ipsilateral (10), R‐Bilateral (9), and R‐Control (12). On preoperative evaluation, memory performance did not differ among surgical groups. Right HS patients did not present postoperative memory decline. L‐Ipsilateral group presented postoperative decline on immediate (P = 0.036) and delayed verbal recall (P = 0.011), while L‐Bilateral did not decline. L‐Ipsilateral had lower RCI Z‐scores, indicating delayed verbal memory decline compared to L‐Bilateral (P = 0.012).

Significance

Dominant HS patients with bilateral ictal involvement presented less pronounced postoperative verbal memory decline compared to patients with exclusive ipsilateral ictal activity. Surgery was indicated in these patients regardless of memory impairment on neuropsychological testing, since resection of the left sclerotic hippocampus could result in cessation of contralateral epileptiform activity, and, therefore, improved memory function.
Reconnaissance Survey of Organic Contaminants of Emerging Concern in the Kabul and Swat Rivers of Pakistan
Authors: Schilling Costello Maria Christina , Asad Neelam , Haris Muhammad , Yousefi Peyman , Khan Bushra , Lee Linda S.
Published: September 2023

The Swat and Kabul rivers of northern Pakistan are within an important regional watershed that supports river-based livelihoods and is impacted by untreated effluent discharges and municipal solid waste. Evidence indicates that fish populations are decreasing in these rivers. One potential cause of poor aquatic health is pollution; therefore, we investigated the presence of contaminants of emerging concern (CECs) in the river systems. Water samples were collected in the Kabul River (n = 9) and Swat River (n = 10) during seasons of high (summer 2018) and low (winter 2019) river flow. Agrochemicals, pharmaceuticals, plasticizers, chemicals in personal care products, and hormones were quantified via liquid chromatography high-resolution mass spectrometry. In the Swat River, caffeine (18–8452 ng/L), N,N-diethyl-meta-toluamide (DEET; 16–56 ng/L), and plasticizers (13–7379 ng/L) were detected at all sites during both seasons, while butachlor (16–98 ng/L) was detected only during high flow. In the Kabul River, caffeine (12–2081 ng/L) and several plasticizers (91–722 ng/L) were detected at all sites during both seasons, while DEET (up to 97 ng/L) was detected only during high flow. During low flow, pharmaceuticals (analgesics and nonsteroidal anti-inflammatory drugs) were quantified in both rivers (up to 823 ng/L), with detection frequencies from 70% to 100% and 0% to 78% in the Swat and Kabul Rivers, respectively. Intermittent-use and natural seasonal processes (increased runoff and dilution from rainfall and snowmelt) yielded higher agrochemical concentrations and lower concentrations of continuous-use compounds (e.g., caffeine) during high flow. The present study provides the first insight into CEC concentrations in the Swat River, additional insight into the Kabul River stressors, and, overall, contaminant risks to aquatic life. Environ Toxicol Chem 2023;42:2599–2613. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

Plasticizers and other chemicals of emerging concern in Pakistan rivers are compromising aquatic ecosystems, thus potentially community livelihoods.
NN‐based method for regulating electrical impulse firing behavior of semiconductor low‐dimensional nanomaterials
Authors: Yang Jun
Published: September 2023

In the process of regulating the electrical pulse emission behavior of polyoxide‐semiconductor low‐vinamethylene material neural network (NN) by adsorption of oxidation/reduction molecules, the electrical pulse behavior in the NN is uncontrollable. In order to develop a new method to solve this problem, we analyze a regulatory method to study the emission behavior of electrical pulses by regulating the charge transfer of oxidation/reduction molecules between polymetalate semiconductors and low‐vinamethylene materials. In this paper, BP neural network is used to process and model the electrical pulse discharge behavior of semiconductor low‐vinamil materials. By establishing the neural network model, the precise control of the electrical pulse emission behavior is realized, and experiments are carried out. The experimental results in this paper show that after using the BP NN to calculate the regulation of the electrical pulse discharge behavior of low‐dimensional nanomaterials, it can be seen that the charge threshold am is 6 when no redox molecules are added. When NH3 is adsorbed, the charge threshold am is 13 according to the change ratio of the corresponding charge barrier height. Through the simulation results of pulse emission recorded by the NN, it can be seen that the amplitude and frequency of electric pulse in a molecular NN are reduced. This research provides new methodological and theoretical support for the development of novel neural networks and intelligent electronic devices based on semiconductor low‐dimensional nanomaterials.
Environmental and farming practice controls of productivity of Cyrtosperma merkusii (giant swamp taro), an underutilised wetland and potential paludiculture crop
Authors: Mendiondo Guillermina , Moko Emma M. , Sparkes Debbie L. , Rahardiyan Dino , Welham Simon J. M. , O'Reilly Patrick , Wilson Paul , Thomas Michelle L. , Ngangi Jantje , Sjögersten Sofie
Published: September 2023

Growing recognition of the potential vulnerabilities of major crop systems has spurred a growing interest in the potential of alternative crops which may be resilient to climate change and also help mitigate its effects. In Indonesia, such issues are particularly pertinent given that country's particular vulnerability to climate change impacts high dependence on agricultural livelihoods and varied topographies and growing conditions. Cyrtosperma merkusii (giant swamp taro) is a wetland plant which has historically formed part of food systems in the eastern Pacific. The plant has the potential to be cultivated as a source of starch on marginal coastal land and on peatlands with high water tables. The aim of this paper was therefore to determine site conditions that promote growth of C. merkusii and the macro and micronutrient status of the corms. Naturally, the size of the plants varied substantially among sites, with a neutral pH, and low redox and conductivity being strong edaphic predictors of corm size. Despite substantial differences in the soil properties of the different study sites, there were no significant differences in the macro and micronutrient content of the corms. Field trials showed that although the plants grew under dry land conditions, the plants grew bigger and yielded corms with greater concentrations of Fe, Mn and K under waterlogged conditions, indicating that a high‐water table is the best cultivation environment for C. merkusii. The nutrient content of the corms suggests that, although primarily a starch crop, C. merkusii could also increase the intake of Fe in populations where Fe deficiency is pervasive. We conclude that the wetland plant C. merkusii has considerable potential as a paludiculture crop in low‐lying areas of SE Asia as it was tolerant of a wide range of soil conditions and performed well when cultivated under waterlogged conditions without additional fertilisation.
A 2D seismic reflection dataset of the Caosiyao giant porphyry Mo deposit in the shallow coverage area in Jining, Inner Mongolia, China
Authors: Lin Kunqi , Zhang Zhenjie , Yang Jie , Chen Guoxiong , Wu Guopeng , Wang Yongzhi , Cheng Qiuming
Published: September 2023

Prospecting for and exploiting buried mineral deposits is currently challenging. Given their high precision and resolution, reflection seismic methods might be useful in such applications involving deep mineral deposits. However, there are few open seismic datasets available from mineral deposit exploration, especially in hardrock environments. The world‐class Caosiyao porphyry Molybdenum deposit (1.76 Mt) in the Jining area of Inner Mongolia, China, is largely covered by loess layers, which poses challenges to its exploration. Seismic reflection surveys were conducted to help delineate the deep granite porphyry intrusions and associated orebodies. This paper presents the raw seismic reflection dataset from three profiles on the Caosiyao deposit area, which can be used as a standard dataset for reflection seismic processing in shallow coverage and hardrock areas. Situated at the juxtaposition of the Khondalite Belt and the Trans‐North China Orogen in the northern North China Craton, the Jining region hosts considerable known porphyry Mo deposits. As such, this open dataset can assist in research on deep geological structures and hence increase prospecting efficiency in geologically similar areas.
Estimation of fMRI responses related to epileptic discharges using Bayesian hierarchical modeling
Authors: Cai Zhengchen , von Ellenrieder Nicolás , Koupparis Andreas , Khoo Hui Ming , Ikemoto Satoru , Tanaka Masataka , Abdallah Chifaou , Rammal Saba , Dubeau Francois , Gotman Jean
Published: September 2023

Simultaneous electroencephalography–functional MRI (EEG‐fMRI) is a unique and noninvasive method for epilepsy presurgical evaluation. When selecting voxels by null‐hypothesis tests, the conventional analysis may overestimate fMRI response amplitudes related to interictal epileptic discharges (IEDs), especially when IEDs are rare. We aimed to estimate fMRI response amplitudes represented by blood oxygen level dependent (BOLD) percentage changes related to IEDs using a hierarchical model. It involves the local and distributed hemodynamic response homogeneity to regularize estimations. Bayesian inference was applied to fit the model. Eighty‐two epilepsy patients who underwent EEG‐fMRI and subsequent surgery were included in this study. A conventional voxel‐wise general linear model was compared to the hierarchical model on estimated fMRI response amplitudes and on the concordance between the highest response cluster and the surgical cavity. The voxel‐wise model overestimated fMRI responses compared to the hierarchical model, evidenced by a practically and statistically significant difference between the estimated BOLD percentage changes. Only the hierarchical model differentiated brief and long‐lasting IEDs with significantly different BOLD percentage changes. Overall, the hierarchical model outperformed the voxel‐wise model on presurgical evaluation, measured by higher prediction performance. When compared with a previous study, the hierarchical model showed higher performance metric values, but the same or lower sensitivity. Our results demonstrated the capability of the hierarchical model of providing more physiologically reasonable and more accurate estimations of fMRI response amplitudes induced by IEDs. To enhance the sensitivity of EEG‐fMRI for presurgical evaluation, it may be necessary to incorporate more appropriate spatial priors and bespoke decision strategies.
Identifying multivariate controls of pan evaporation variations in subregions of Yangtze River Basin using multiple wavelet coherence
Authors: Yang Ronghua , He Xinguang , Li Jiajia , Zhang Cicheng , Zhang Xinping
Published: September 2023

In this study, temporal variations of pan evaporation (PE) and its optimal combination of controlling factors are investigated in the subregions of Yangtze River Basin (YRB) by using multiple wavelet coherence (MWC). For this purpose, the YRB is firstly divided into nine relatively homogeneous PE subregions by combining empirical orthogonal functions with fuzzy C‐means clustering. After regionalization, temporal variations of regional PE are analysed in each of subregions. Results reveal that regional annual PE has an upward trend in all subregions, and seasonal PE in almost the subregions for four different seasons. The wavelet transform coherence (WTC) analysis shows that vapour pressure deficit (VPD) is the primary controlling factor of PE variations in all subregions. In single factor analysis, VPD, sunshine duration (SSD) and 0 cm ground temperature (ZGT) have a higher covariance with PE than other influencing factors. For two‐factor analysis, the APS (air pressure)‐VPD combination, and for three‐factor analysis, the AWS (average wind speed)‐ ZGT‐VPD combination are the most common best explanatory variables on PE variations. A comparison of the results from the WTC and MWC indicates that PE variations can be explained more accurately by one, two, or three controlling factors. The combination of factors that optimally explains PE variations largely varies with subregions but with VPD as a dominant factor either alone or in combination for all subregions. Moreover, the optimal factor combination for a subregion is not necessarily combined by the first, second and/or third dominant factors for that subregion. Our results can provide useful insights into how multiple temporal dependency of PE is linked with meteorological factors in subregions of the YRB, particularly for PE modelling under changing climate conditions.
Alteration of indicator gut microbiota in patients with chronic sinusitis
Authors: Michalik Michał , Podbielska‐Kubera Adrianna , Basińska Anna Maria , Szewc Monika , Gałęcka Mirosława , Schwiertz Andreas
Published: September 2023

Background

Many factors influence the composition of the sinus microflora. The microbial balance is most disturbed by the use of antibacterial agents. Superinfections caused by more than one pathogen may then occur. Despite treatment, including surgery and long‐term antibiotic therapy, many patients with sinusitis do not experience significant relief from their symptoms. It has been hypothesized that an imbalance in the gut microbiota may also be responsible for the chronicity of sinusitis. Our goal was therefore to identify selected gut indicator bacteria that play a role in immunity in patients with chronic sinusitis. In addition, compare the number of selected bacteria in two groups of patients: with chronic sinusitis and with chronic rhinosinusitis (CRS) with concomitant diseases and/or symptoms other than CRS.

Results

Significantly decreased numbers of Bifidobacterium spp. and Faecalibacterium prauznitzi bacteria were observed in patients from the G1 group. The majority of patients from this group (12 out of 13) had a significantly decreased number of Bifidobacterium and Akkermansia muciniphila bacteria, which are involved in the nutrition and regeneration of gut epithelium cells and have anti‐inflammatory properties. In group G2 (patients with chronic sinusitis and symptoms of comorbidities) a decreased number of F. prausnitzii, Bifidobacterium spp., A. muciniphila and Lactobacillus spp. bacteria was observed. A small percentage of patients in this group showed overgrowth of yeast‐like fungi.

Conclusion

Although the more research is needed, possibly the gut microbiota indicator bacteria number analyses might enable to plan personalized prebiotic and probiotic treatment, which could support intestine microbiota and mucosal immunity patients suffering from chronic sinusitis.
Finance and local economic growth: New evidence from China
Authors: Chen Jingzhu , Ji Yuemei
Published: September 2023

We study the relationship between finance and growth using a sample of 275 Chinese cities from 2009 to 2018. We exclude bank loans to local governments through the local government financing vehicles (LGFVs) and construct a better financial development index which measures the level of loans extended by banks to enterprises and households. We find that financial development in the form of a higher loan‐to‐GDP ratio leads to lower economic growth. This negative relationship between finance and growth may be attributed to various mechanisms, including discrimination in bank lending, housing market bubbles, and an imbalance in growth between real and financial sectors.
Using a crop water stress index to determine water use efficiency in a raspberry crop in the Mediterranean Central Chile
Authors: Vargas‐Castro Catherine , Mattar Cristian , Seguel Oscar , Moletto‐Lobos Ítalo
Published: September 2023

Water availability is projected to decrease in Mediterranean Central Chile, necessitating sustainable production strategies based on improved irrigation management. This study focuses on estimating water use efficiency (WUE) in raspberry crops at two validation sites using remote sensing and soil irrigation data. By employing the crop water stress index (CWSI), we demonstrate the potential of this tool in enhancing irrigation management and establishing sustainable production practices. The results demonstrate the successful estimation of actual evapotranspiration (ETa) using the Operational Simplified Surface Energy Balance (SSEBop) model (coefficient of determination [R2] = 0.92; root mean square error [RMSE] = 0.97 mm day−1), while the CWSI indicated high stress levels after 5 days of irrigation. Moreover, validation at two sites reveals significant differences in applied irrigation, with sites A and B receiving 17,097 and 3760 m3 ha−1, respectively, while the average water demand is close to 5300 m3 ha−1. These variations result in discrepancies in WUE, with values of 0.79 and 3.64 kg m−3. By integrating remote sensing indices and soil data, this study proposes that maintaining an 85% ETa rate during noncritical periods can enhance WUE. This work demonstrates the potential use of a water stress index to monitor crops in the Chilean central zone for efficient water resource use under future scarcity scenarios.
Anti‐Proliferative Effect of the Kinase Inhibitor K252a on Human Prostatic Carcinoma Cell Lines
Authors: DELSITE ROBERT , DJAKIEW DANIEL
Published: September 2023

ABSTRACT: Members of the K252 family of kinase inhibitors have been demonstrated to inhibit a number of neurotrophin‐mediated cellular responses, and to preferentially inhibit the activity of neurotrophin receptors. In this study, we examined the effects of K252a and K252b on the growth of human prostate carcinoma cells, whose growth is, in part, mediated by a prostatic nerve growth factor (NGF)‐ like protein(s). K252a inhibited [3H]thymidine incorporation by three androgen‐independent prostate tumor cell lines (TSU‐pr1, DU‐145, and PC‐3), under basal growth conditions, and in response to growth stimulation by human prostatic stromal (hPS) cell proteins and serum. K252b, which does not readily penetrate cell membranes, had no significant effect on [3H]thymidine incorporation by the prostate tumor cell lines. The decrease in [3H]thymidine incorporation by the cell lines in response to K252a did not appear to be the result of K252a cytotoxicity at concentrations as high as 100 nM, as measured by the Trypan blue assay for cell viability. Treatment of cells for 25 hours with 100 nM K252a resulted in accumulation of TSU‐pr1, DU‐145, and PC‐3 cells in G0/G1, concurrent with a substantial decrease in cells synthesizing DNA. Treatment of androgen‐responsive LNCaP prostatic carcinoma cells for 25 hours with 100 nM K252a also resulted in a significant decrease in DNA synthesis. Human recombinant NGF‐mediated phosphorylation of a 140‐kDa Trk NGF receptor in the TSU‐pr1 cell line was inhibited by treatment with 100 nM K252a. Hence, K252a inhibition of Trk phosphorylation most probably contributed, in part, to the inhibition of prostate tumor cell growth in vitro. These results suggest that the mechanism of K252a action may be useful in the design of potential therapies for prostate cancer treatment.
Differential Expression of Clusterin in the Testis and Epididymis of Postnatal and Germ Cell Deficient Mice
Authors: AHUJA HARLEEN SINGH , TENNISWOOD MARTIN , ZAKERI ZAHRA E
Published: September 2023

ABSTRACT:Clusterin is found in a wide variety of tissues and is expressed in a number of physiological and pathological contexts. It is expressed constitutively in the adult male reproductive tract, specifically the testes and caput of the epididymis. The gene is also induced during apoptotic cell death in the kidney and hormone‐dependent tissues such as the prostate and mammary gland. The mechanisms controlling the expression of clusterin gene expression in these tissues are still unknown, although it has been suggested that interactions between the Sertoli cells and germ cells in the testis, or epithelial cells and germ cells in the epididymis, may be required for clusterin expression. To investigate the importance of germ cells in the induction of clusterin expression in these tissues, we have usedin situhybridization to determine the developmental regulation and germ cell dependence of clusterin expression in the reproductive tract of the normal and germ cell deficient male mice. Clusterin mRNA is present in the supporting cells in the testes of normal mice and in both atrichosis (at) and dominant spotting mutant (Wv) mice, both of which are germ cell deficient. On the other hand, the expression of clusterin in the epididymis appears to be at least partially dependent of the presence of germ cells, because segmental localization of clusterin mRNA within the caput of the epididymis that is seen in normal mice is disrupted in theatandWvmutants. In these germ cell deficient mutants, the steady‐state level of clusterin mRNA, which is repressed in segment 1 and 2 of the adult wild type mouse, is expressed at levels similar to those seen at days 7 and 17 during the development of the normal epididymis.
Reassessing growth vulnerability
Authors: Cho Dooyeon , Rho Seunghwa
Published: September 2023

This paper replicates the results of Adrian et al. (American Economic Review, 2019) that GDP growth volatility is mainly driven by the lower quantiles of the distribution which is predicted by the financial condition. It extends their study by estimating the model with the IVX‐QR estimator of Lee (Journal of Econometrics, 2016) and double weighted estimator of Cai et al. (Journal of Econometrics, 2022) considering that the financial condition index is highly serially correlated. Both models are estimated with the smoothed estimating equation approach of Kaplan and Sun (Econometric Theory, 2017). The results show that the findings of Adrian et al. (American Economic Review, 2019) are robust to possible bias due to the existence of persistent predictors. The out‐of‐sample forecasting exercises suggest that methods that are robust to the existence of persistent predictors can improve forecasting performance at the lower quantiles of the GDP growth distribution.
Magnetic hydrogel applications in articular cartilage tissue engineering
Authors: Taghizadeh Saeed , Tayebi Lobat , Akbarzadeh Majid , Lohrasbi Parvin , Savardashtaki Amir
Published: September 2023

Articular cartilage defects afflict millions of individuals worldwide, presenting a significant challenge due to the tissue's limited self‐repair capability and anisotropic nature. Hydrogel‐based biomaterials have emerged as promising candidates for scaffold production in artificial cartilage construction, owing to their water‐rich composition, biocompatibility, and tunable properties. Nevertheless, conventional hydrogels typically lack the anisotropic structure inherent to natural cartilage, impeding their clinical and preclinical applications. Recent advancements in tissue engineering (TE) have introduced magnetically responsive hydrogels, a type of intelligent hydrogel that can be remotely controlled using an external magnetic field. These innovative materials offer a means to create the desired anisotropic architecture required for successful cartilage TE. In this review, we first explore conventional techniques employed for cartilage repair and subsequently delve into recent breakthroughs in the application and utilization of magnetic hydrogels across various aspects of articular cartilage TE.
Effect of Hepatic Impairment on the Pharmacokinetics of Nirmatrelvir/Ritonavir, the First Oral Protease Inhibitor for the Treatment of COVID‐19
Authors: Singh Ravi Shankar P. , LaBadie Robert R. , Toussi Sima S. , Shi Haihong , Berg Jolene Kay , Neutel Joel M. , Aggarwal Sudeepta
Published: September 2023

Nirmatrelvir, a novel, potent, orally bioavailable severe acute respiratory syndrome coronavirus 2 main protease inhibitor, coadministered with ritonavir for pharmacokinetic (PK) enhancement is licensed for the treatment of mild to moderate COVID‐19 in individuals at increased risk of progression to severe disease. Cytochrome P450 3A4 is the primary metabolic enzyme responsible for nirmatrelvir metabolism; however, when cytochrome P450 3A4 is inhibited by ritonavir, nirmatrelvir is primarily excreted, unchanged, in urine. Because of intended use of nirmatrelvir among individuals with hepatic impairment, this Phase 1 study (NCT05005312) evaluated the effects of hepatic impairment on nirmatrelvir PK parameters to assess the potential need for any dose adjustments in this population. Participants with normal hepatic function or moderate hepatic impairment (n = 8 each) were administered a single 100‐mg nirmatrelvir dose, with 100 mg of ritonavir administered 12 hours before, together with, and 12 and 24 hours after nirmatrelvir. Nirmatrelvir median plasma concentrations and systemic exposure measured by area under the plasma concentration–time curve from time zero extrapolated to infinite time and maximum observed plasma concentration values were comparable in both groups. Nirmatrelvir/ritonavir had an acceptable safety profile in both groups, and no clinically significant changes in laboratory measurements, vital signs, or electrocardiogram assessments were observed. Based on these results, no dose adjustment is deemed necessary in patients with moderate hepatic impairment and, by extension, in patients with mild hepatic impairment.
The right not to know: Non‐disclosure of primary genetic test results and genetic counselors' response
Authors: Murphy Claire , Sturm Sarah , McKenna Meghan Juliana , Ormond Kelly E.
Published: September 2023

As part of clinical genetic counseling practice, patients may request that their primary genetic test results be disclosed to someone else, such as a relative or referring provider, or request that results be disclosed to no one (non‐disclosure). In making these requests, patients employ the ethical principle of the “right not to know,” which argues that autonomous individuals can choose not to know relevant health information. Although the right not to know has been well‐studied in medicine in general, and in the return of genomic secondary findings, we are not aware of other studies that have explored the return of primary genetic test results when patients request non‐disclosure or disclosure to another individual. This study aimed to describe common clinical scenarios in which these requests occur, how genetic counselors respond, and what ethical considerations they employ in their decision‐making process. We recruited participants from the National Society of Genetic Counselors' (NSGC) “Student Research Surveys and Reminders” listserv and conducted semi‐structured interviews with 11 genetic counselors in the United States who described genetic counseling cases where this occurred. Interviews were transcribed and coded inductively, and themes were identified. Case details varied, but in our study data the requests for non‐disclosure were most commonly made by patients with poor, often oncologic, prognoses who requested their test results be disclosed to a family member instead of themselves. Genetic counselors considered similar factors in deciding how to respond to these requests: patient autonomy, medical actionability of results for the patient and family, the relationship between the patient and the person to whom results might be disclosed, and legal or practical concerns. Genetic counselors often made decisions on a case‐by‐case basis, depending on how relevant each of these factors were. This study adds to the growing body of literature regarding patients' “right not to know” and will hopefully provide guidance for genetic counselors who experience this situation in clinical practice.
The binding profile of SARS‐CoV‐2 with human leukocyte antigen polymorphisms reveals critical alleles involved in immune evasion
Authors: Zhan Yan , Ye Ling , Ouyang Qianying , Yin Jiye , Cui Jiajia , Liu Ke , Guo Chengxian , Zhang Haibo , Zhai Jingbo , Zheng Chunfu , Guo Aoxiang , Sun Bao
Published: September 2023

The COVID‐19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), astonished the world and led to millions of deaths. Due to viral new mutations and immune evasion, SARS‐CoV‐2 ranked first in transmission and influence. The binding affinity of human leukocyte antigen (HLA) polymorphisms to SARS‐CoV‐2 might be related to immune escape, but the mechanisms remained unclear. In this study, we obtained the binding affinity of SARS‐CoV‐2 strains with different HLA proteins and identified 31 risk alleles. Subsequent structural predictions identified 10 active binding sites in these HLA proteins that may promote immune evasion. Particularly, we also found that the weak binding ability with HLA class I polymorphisms could contribute to the immune evasion of Omicron. These findings suggest important implications for preventing the immune evasion of SARS‐CoV‐2 and providing new insights for the vaccine design.
Associated factors and outcomes of crossover from a laser sheath to a bidirectional rotational mechanical sheath during transvenous lead extraction
Authors: Isawa Tsuyoshi , Honda Taku , Yamaya Kazuhiro , Toyoda Shigeru , Taguri Masataka
Published: September 2023

Background

During transvenous lead extraction (TLE), a GlideLight laser sheath (Philips) cannot always be advanced over the lead, and crossover to the Evolution system (i.e., an Evolution RL sheath or Evolution Shortie RL sheath [Cook Medical]) is required. We aimed to determine the associated factors and outcomes of such device crossover.

Methods

This observational study included 112 patients who underwent TLE. The patients were divided into crossover and non‐crossover groups. Outcomes and associated factors of crossover were evaluated.

Results

Overall, 57 (50.9%) patients required crossover to the Evolution system (crossover group), whereas 55 (49.1%) patients did not require crossover (non‐crossover group). Clinical success rate was similar between the two groups (98.3% vs. 100%; p = 1.00). No major intraprocedural complications related to powered sheaths occurred. Multivariate logistic regression analysis results showed that dwell time of the oldest extracted lead (per year) (odds ratio [OR]: 1.18, 95% confidence interval [CI]: 1.02–1.36; p = .026), number of leads extracted per procedure (OR: 7.23, 95% CI: 1.74–29.99; p = .007), and use of a femoral approach (OR: 21.09, 95% CI: 2.33–190.67; p = .007) were associated factors of crossover. The cutoff for crossover was 7.7 years from the implant (sensitivity 90.5%, specificity 64.9%, area under the curve 0.80).

Conclusions

Both groups showed a high rate of clinical success. Switching to the Evolution system may facilitate a safe and effective TLE when a laser sheath does not advance despite laser activation.
Evaluation of Post‐Intervention Outcomes in Patients with Empty Nose Syndrome
Authors: Kim Do Hyun , Kim Sung Won , Basurrah Mohammed Abdullah , Hwang Se Hwan
Published: September 2023

Objectives

To conduct a systematic review and meta‐analysis of published articles to assess the impact of inferior turbinate/meatus augmentation in patients diagnosed with empty nose syndrome (ENS).

Data Sources

PubMed, Cochrane database, Embase, Web of Science, SCOPUS, and Google Scholar.

Review Methods

Six databases were searched to December 2022. We retrieved studies evaluating improvements in refractory ENS‐related symptoms based on various patient‐reported outcome measures after inferior turbinate/meatus augmentation.

Results

As a result of meta‐analysis, Sinonasal Outcome Test, Empty Nose Syndrome 6‐Item Questionnaire (ENS6Q), and depression scores were measured at 1 week; 1, 3, and 6 months; and later than 12 months after intervention for patients with ENS. All scores revealed significant symptom improvement. By reference to the minimal clinically important difference of the ENS6Q (6.25), inferior turbinate/meatus augmentation relieved the nasal symptoms of ENS in the long term. Although the improvements in anxiety scores at 1 week (0.4133 [−0.3366; 1.1633], 0.00, I2 = NA) and 1 month (0.4525 [−0.0529; 0.9579], I2 = 0.0%) were not statistically significant, the scores differed significantly at 3 months (0.7351 [0.4143; 1.0559], I2 = 28.4%), 6 months (0.8297 [0.6256; 1.0337], I2 = 37.2%), and longer than 12 months (0.7969 [0.4768; 1.1170], I2 = 0.0%).

Conclusion

These data and analysis suggest that performing inferior turbinate/meatus augmentation on ENS patients may improve not only nasal symptom scores but also accompanying psychological problems such as anxiety and depression. Laryngoscope, 134:2005–2011, 2024
Rational of topical photodynamic therapy (PDT) with 5‐aminolevulinic acid (5‐ALA) for treatment of endocervical canal low‐grade squamous intraepithelial lesion with high‐risk human papillomavirus infection
Authors: Yuan Lin‐Jing , He Ke , Zhu Cai‐Xia , Cao Tie‐Feng , He Mian
Published: September 2023

Background

The detection and continuous monitoring of low‐grade squamous intraepithelial lesions (LSIL) within the endocervical canal pose considerable challenges, and the effectiveness of ablation treatment is also constrained. In this context, the potential efficacy of 5‐aminolevulinic acid photodynamic therapy (5‐ALA PDT) in targeting these concealed lesions merits exploration. The present study undertakes a comprehensive analysis of the clinical effectiveness and safety aspects associated with the utilization of 5‐ALA PDT.

Methods

A retrospective analysis was conducted on a cohort of 13 patients who were diagnosed with LSIL within the endocervical canal, concomitant with high‐risk human papillomavirus (hrHPV) infection. These patients were subjected to treatment with 5‐ALA PDT and subsequently monitored over a period of 3−6 months following the intervention.

Results

The study cohort comprised 13 patients, among whom 4 presented with isolated lesions within the endocervical canal, 5 exhibited LSIL involving both the endocervical canal and the cervix vaginal portion, 3 displayed LSIL within the endocervical canal in conjunction with vaginal involvement, and 1 patient demonstrated lesions across all three of these anatomical sites. All identified lesions underwent therapeutic intervention via 5‐ALA PDT. Before treatment initiation, 9 patients returned positive results in the liquid‐based cytologic test (LBC), 4 displayed concurrent multiple hrHPV infections, and 5 manifested infections specifically with HPV 16/18. Subsequent to the application of 5‐ALA PDT, regression was observed in the LBC results of all patients, with only 3 individuals retaining a singular type of hrHPV infection. Adverse reactions following treatment encompassed mild aberrant vaginal secretions and mild to moderately pronounced distending abdominal discomfort, all of which were remitted within a span of 7 days.

Conclusions

Within the context of LSIL within the endocervical canal in association with hrHPV infection, the findings affirm the efficacy and safety of 5‐ALA PDT as a viable therapeutic modality.
Customer benefits and value creation in streaming services marketing: a managerial cognitive capability approach
Authors: Chen Yi‐Min , Liu Hsin‐Hsien , Chiu Yu‐Chun
Published: September 2023

Customer value analysis and management is a key theoretical and empirical issue in marketing management and strategic management. However, little is known about the influence of customer benefit on customer value from the microfoundations of the dynamic capabilities perspective. Currently, a boom in online video and music streaming services is changing the entertainment industry structure. Thus, marketing managers in the fast‐growing streaming services industry should have dynamic managerial capabilities to anticipate other service elements that customers consider valuable. Based on managerial cognitive dynamic capabilities, this research explored the influences of customer‐perceived functional benefit, experiential benefit, financial benefit, and psychosocial benefit on perceived instrumental and terminal values. General linear model (GLM) and fuzzy‐set qualitative comparative analysis (fsQCA) were conducted to gain a more nuanced understanding of how different customers’ perceived benefits have different impacts on perceived value. The findings illuminate complex benefit configurations that drive perceived instrumental and terminal values and contribute to the development of value creation and its drivers. The proposed framework can help managers develop managerial cognitive dynamic capabilities by increasing their understanding of the impact of different perceived benefits on value creation for different types of customers.
Characterization of concomitant gradient fields and their effects on image distortions using a low‐field point‐of‐care Halbach‐based MRI system
Authors: de Vos Bart , Remis Rob F. , Webb Andrew G.
Published: September 2023

Purpose

Concomitant gradient fields have been extensively studied at clinical field strengths. However, their effects have not yet been modeled for low‐field point‐of‐care (POC) systems. The purpose of this work is to characterize the effects associated with concomitant fields for POC Halbach‐array‐based systems.

Methods

The concomitant fields associated with a cylindrical gradient coils designed for a transverse and a signal model including the tilting effect of the effective magnetic field are derived. The formalism is used to simulate and predict concomitant field related distortions. A 46‐mT Halbach‐array‐based system with a maximum gradient strength of 15 mT/m is used to verify the model using two‐dimensional spin‐echo sequences.

Results

The simulations and experimental results are in good agreement with the derived equations. The fundamental characteristics of the concomitant field equations are different to conventional MRI systems: Image distortions occur primarily in the transverse directions and a cross‐term only exists when applying transverse gradient pulses simultaneously.

Conclusion

The level of image warping in the frequency encoding direction is insignificant for the POC systems discussed here. However, when trying to achieve short echo‐times by using strong phase encoding and readout‐dephasing gradients, the combination can result in image warping and blurring which should be accounted for in image interpretation.
Simultaneous perfusion, diffusion, T2*, and T1 mapping with MR fingerprinting
Authors: Fan Hongli , Bunker Lisa , Wang Zihan , Durfee Alexandra Zezinka , Lin Doris , Yedavalli Vivek , Ge Yulin , Zhou Xiaohong Joe , Hillis Argye E. , Lu Hanzhang
Published: September 2023

Purpose

Quantitative mapping of brain perfusion, diffusion, T2*, and T1 has important applications in cerebrovascular diseases. At present, these sequences are performed separately. This study aims to develop a novel MRI technique to simultaneously estimate these parameters.

Methods

This sequence to measure perfusion, diffusion, T2*, and T1 mapping with magnetic resonance fingerprinting (MRF) was based on a previously reported MRF‐arterial spin labeling (ASL) sequence, but the acquisition module was modified to include different TEs and presence/absence of bipolar diffusion‐weighting gradients. We compared parameters derived from the proposed method to those derived from reference methods (i.e., separate sequences of MRF‐ASL, conventional spin‐echo DWI, and T2* mapping). Test–retest repeatability and initial clinical application in two patients with stroke were evaluated.

Results

The scan time of our proposed method was 24% shorter than the sum of the reference methods. Parametric maps obtained from the proposed method revealed excellent image quality. Their quantitative values were strongly correlated with those from reference methods and were generally in agreement with values reported in the literature. Repeatability assessment revealed that ADC, T2*, T1, and B1+ estimation was highly reliable, with voxelwise coefficient of variation (CoV) <5%. The CoV for arterial transit time and cerebral blood flow was 16% ± 3% and 25% ± 9%, respectively. The results from the two patients with stroke demonstrated that parametric maps derived from the proposed method can detect both ischemic and hemorrhagic stroke.

Conclusion

The proposed method is a promising technique for multi‐parametric mapping and has potential use in patients with stroke.
Farmers' green technology adoption: Implications from government subsidies and information sharing
Authors: Hong Xianpei , Chen Ying‐Ju , Gong Yeming , Wang Hua
Published: September 2023

While the previous literature on green technology adoption has not fully considered information sharing, we consider the impact of demand information sharing on the adoption of green technologies by risk‐averse farmers in a vertical agricultural supply chain. We find that government subsidies and information sharing do not always promote farmers' adoption of green technologies. The accuracy of the information plays a vital role in promoting farmers' adoption of green technologies; however, the increased green technology adoption induced by more accurate information may be detrimental to farmer welfare in the presence of production diseconomies. Information sharing can reduce the amount of government subsidies for promoting green technology adoption, thereby suggesting the substitutable role of information and monetary instruments. Nonetheless, information‐sharing may lead to lower water savings and thus should be adopted with caution. Risk aversion has a nontrivial impact on agricultural technology adoption: farmers are more likely to adopt traditional agricultural technologies when their risk aversion is either very low or very high. Finally, we validate our decision model with U.S. Department of Agriculture cotton production data and propose management insights to help farmers make appropriate adoption decisions under information asymmetry and risk‐averse attitudes.