bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive dysfunction and the 25‐item National Eye Institute Visual Function Questionnaire
Authors: Mozdbar Sima , Alber Jessica , Aryal Subhash , Johnson Leigh , Moroz Alina , Rashik Mohammad , Mostafavi Amir , O'Bryant Sid
Published: November 2022

Introduction

Visual function and cognitive impairment are interrelated; however, little is known about the impact of modifying treatable vision impairment on the development of cognitive dysfunction. This study examines the relationship between cognition and self‐reported visual function using the National Eye Institute's Visual Function Questionnaire (NEI VFQ).

Methods

Participants completed the NEI VFQ 25‐Item questionnaire as well as the Mini‐Mental State Examination (MMSE). Additionally, all participants were assigned a consensus clinical diagnosis based on established criteria. We used a general linear model and analysis of variance approach to compare means between multiple groups.

Results

A significant association between overall composite score on the NEI VFQ and total MMSE score was revealed (P = 0.04). On average, for every 1‐point increase in MMSE score, the overall composite score increased by 0.40 units (95% confidence interval: 0.03–0.77).

Discussion

Reduced visual function should raise concerns about cognitive decline and prompt additional assessment.
In vitro enzymatic evaluation of some pyrazolo[1,5‐a]pyrimidine derivatives: Design, synthesis, antioxidant, anti‐diabetic, anti‐Alzheimer, and anti‐arthritic activities with molecular modeling simulation
Authors: Hassan Ashraf S. , Morsy Nesrin M. , Aboulthana Wael M. , Ragab Ahmed
Published: November 2022

The strategy of utilizing nitrogen compounds in various biological applications has recently emerged as a powerful approach to exploring novel classes of therapeutics to face the challenge of diseases. A series of pyrazolo[1,5‐a]pyrimidine‐based compounds 3a–l and 5a–f were prepared by the direct cyclo‐condensation reaction of 5‐amino‐1H‐pyrazoles 1a, b with 2‐(arylidene)malononitriles and 3‐(dimethylamino)‐1‐aryl‐prop‐2‐en‐1‐ones, respectively. The structures of the new pyrazolo[1,5‐a]pyrimidine compounds were confirmed via spectroscopic techniques. The in vitro biological activities of all pyrazolo[1,5‐a]pyrimidines 3a–l and 5a–f were evaluated by assaying total antioxidant capacity, iron‐reducing power, the scavenging activity against 1‐diphenyl‐2‐picryl‐hydrazyl (DPPH) and 2, 2'‐azinobis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) radicals, anti‐diabetic, anti‐Alzheimer, and anti‐arthritic biological activities. All compounds displayed good to potent bioactivity, and three compounds 3g, 3h, and 3l displayed the most active derivatives. Among these derivatives, compound 3l exhibited the highest antioxidant (total antioxidant capacity [TAC] = 83.09 mg gallic acid/g; iron‐reducing power [IRP] = 47.93 µg/ml) and free radicals scavenging activities with (DPPH = 18.77 µg/ml; ABTS = 40.44%) compared with ascorbic acid (DPPH = 4.28 µg/ml; ABTS = 38.84%). Furthermore, compound 3l demonstrated the strongest inhibition of α‐amylase with a percent inhibition of 72.91 ± 0.14 compared to acarbose = 67.92 ± 0.09%. Similarly, it displayed acetylcholinesterase inhibition of 62.80 ± 0.06%. However, compound 3i showed a significantly higher inhibition percentage for protein denaturation and proteinase at 20.66 ± 0.00 and 26.42 ± 0.06%, respectively. Additionally, some in silico ADMET properties were predicted and studied. Finally, molecular docking simulation was performed inside the active site of α‐amylase and acetylcholinesterase to study their interactions.
Psychometric properties of the Eating Disorder Examination Questionnaire among Brazilian cisgender gay and bisexual adult men
Authors: de Oliveira Júnior Mauro Lúcio , Almeida Maurício , Santos Cleonaldo Gonçalves , Brown Tiffany A. , de Carvalho Pedro Henrique Berbert
Published: November 2022

Objective

One of the most widely used assessment tools for disordered eating attitudes and behaviors, the Eating Disorder Examination Questionnaire (EDE‐Q), has not yet been evaluated in Brazilian cisgender gay and bisexual men—an at‐risk population given the extent of minority stressors in Brazilian culture. The present study aimed to assess the psychometric properties of the EDE‐Q among Brazilian cisgender gay and bisexual adult men.

Method

The Brazilian EDE‐Q was administered to a sample of 1409 gay and bisexual adult men, along with measures of self‐objectification, body‐ideal internalization, drive for muscularity, muscle dysmorphia symptoms, and body appreciation. The factor structure of the Brazilian EDE‐Q was assessed using a two‐step, split‐sample exploratory (EFA; n = 704) and confirmatory factor analytic approach (CFA; n = 705). Additionally, convergent validity, internal consistency, and 2‐week test–retest reliability were assessed.

Results

Findings from an EFA and CFA revealed a one‐factor structure with 22 items and adequate internal consistency (ω = .92, 95% CI = [.91, .93]). Moreover, the scale demonstrated good 2‐week test–retest reliability (ICC = .86, 95% CI = [.82, .88], p < .001). The EDE‐Q scores showed positive associations with self‐objectification, body‐ideal internalization, muscle dysmorphia symptoms, and drive for muscularity, as well as a negative association with body appreciation.

Discussion

Results provide support for the use of the EDE‐Q using a one‐factor structure in Brazilian cisgender gay and bisexual adult men and give insights for future studies on eating disorders in sexual minorities in Latin America.

Public Significance

The Eating Disorder Examination Questionnaire (EDE‐Q) is one of the most widely used self‐report measures of eating disorder symptoms. However, there is a lack of research on the validity and reliability of the EDE‐Q in Latin American countries. This study evaluated the validity and reliability of the EDE‐Q in Brazilian cisgender gay and bisexual adult men. Our findings give insights for future studies on eating disorders in sexual minorities in Latin America.
Lack of evidence for a fine‐scale magnetic map sense for fall migratory Eastern North American monarch butterflies (Danaus plexippus)
Authors: Guerra Patrick A. , Parlin Adam F. , Matter Stephen F.
Published: November 2022

How first‐time animal migrants find specific destinations remains an intriguing ecological question. Migratory marine species use geomagnetic map cues acquired as juveniles to aide long‐distance migration, but less is known for long‐distance migrants in other taxa. We test the hypothesis that naïve Eastern North American fall migratory monarch butterflies (Danaus plexippus), a species that possesses a magnetic sense, locate their overwintering sites in Central Mexico using inherited geomagnetic map cues. We examined whether overwintering locations and the abundance of monarchs changed with the natural shift of Earth's magnetic field from 2004 to 2018. We found that migratory monarchs continued to overwinter at established sites in similar abundance despite significant shifts in the geomagnetic field, which is inconsistent with monarchs using fine‐scale geomagnetic map cues to find overwintering sites. It is more likely that monarchs use geomagnetic cues to assess migratory direction rather than location and use other cues to locate overwintering sites.
The effects of an obesogenic diet on behavior and cognition in zebrafish (Danio rerio): Trait average, variability, repeatability, and behavioral syndromes
Authors: Anwer Hamza , O'Dea Rose E. , Mason Dominic , Zajitschek Susanne , Klinke Annabell , Reid Madeleine , Hesselson Daniel , Noble Daniel W. A. , Morris Margaret J. , Lagisz Malgorzata , Nakagawa Shinichi
Published: November 2022

The obesity epidemic, largely driven by the accessibility of ultra‐processed high‐energy foods, is one of the most pressing public health challenges of the 21st century. Consequently, there is increasing concern about the impacts of diet‐induced obesity on behavior and cognition. While research on this matter continues, to date, no study has explicitly investigated the effect of obesogenic diet on variance and covariance (correlation) in behavioral traits. Here, we examined how an obesogenic versus control diet impacts means and (co‐)variances of traits associated with body condition, behavior, and cognition in a laboratory population of ~160 adult zebrafish (Danio rerio). Overall, an obesogenic diet increased variation in several zebrafish traits. Zebrafish on an obesogenic diet were significantly heavier and displayed higher body weight variability; fasting blood glucose levels were similar between control and treatment zebrafish. During behavioral assays, zebrafish on the obesogenic diet displayed more exploratory behavior and were less reactive to video stimuli with conspecifics during a personality test, but these significant differences were sex‐specific. Zebrafish on an obesogenic diet also displayed repeatable responses in aversive learning tests whereas control zebrafish did not, suggesting an obesogenic diet resulted in more consistent, yet impaired, behavioral responses. Where behavioral syndromes existed (inter‐class correlations between personality traits), they did not differ between obesogenic and control zebrafish groups. By integrating a multifaceted, holistic approach that incorporates components of (co‐)variances, future studies will greatly benefit by quantifying neglected dimensions of obesogenic diets on behavioral changes.
Cross validation for model selection: A review with examples from ecology
Authors: Yates Luke A. , Aandahl Zach , Richards Shane A. , Brook Barry W.
Published: November 2022

Specifying, assessing, and selecting among candidate statistical models is fundamental to ecological research. Commonly used approaches to model selection are based on predictive scores and include information criteria such as Akaike's information criterion, and cross validation. Based on data splitting, cross validation is particularly versatile because it can be used even when it is not possible to derive a likelihood (e.g., many forms of machine learning) or count parameters precisely (e.g., mixed‐effects models). However, much of the literature on cross validation is technical and spread across statistical journals, making it difficult for ecological analysts to assess and choose among the wide range of options. Here we provide a comprehensive, accessible review that explains important—but often overlooked—technical aspects of cross validation for model selection, such as: bias correction, estimation uncertainty, choice of scores, and selection rules to mitigate overfitting. We synthesize the relevant statistical advances to make recommendations for the choice of cross‐validation technique and we present two ecological case studies to illustrate their application. In most instances, we recommend using exact or approximate leave‐one‐out cross validation to minimize bias, or otherwise k‐fold with bias correction if k < 10. To mitigate overfitting when using cross validation, we recommend calibrated selection via our recently introduced modified one‐standard‐error rule. We advocate for the use of predictive scores in model selection across a range of typical modeling goals, such as exploration, hypothesis testing, and prediction, provided that models are specified in accordance with the stated goal. We also emphasize, as others have done, that inference on parameter estimates is biased if preceded by model selection and instead requires a carefully specified single model or further technical adjustments.
Successful conservative management of left ventricular assist device candidates
Authors: Havakuk Ofer , Hochstadt Aviram , Sadon Sapir , Laurel Perl Michal , Sadeh Ben , Milwidsky Assi , Ran Sapir Orly , Granot Yoav , Lupu Lior , Levi Erez , Farkash Ariel , Ben Gal Yanai , Banai Shmuel , Topilsky Yan
Published: November 2022

Aims

Clinical trials comparing LVADs vs. conservative therapy were performed before the availability of novel medications or used suboptimal medical therapy. This study aimed to report that long‐term stabilization of patients entering a left ventricular assist device (LVAD) programme is possible with the use of aggressive conservative therapy. This is important because the excellent clinical stabilization provided by LVADs comes at the expense of significant complications.

Methods and results

This study was a single‐centre prospective evaluation of consecutive patients with advanced heart failure (HF) fulfilling criteria for LVAD implantation based on clinical and echocardiographic characteristics, cardiopulmonary exercise test, and right heart catheterization results. Their initial therapy included inotropes, thiamine, beta‐blockers, digoxin, spironolactone, hydralazine, and nitrates followed by the introduction of novel HF therapies. Coronary revascularization and cardiac resynchronization therapy were performed when indicated, and all patients were closely followed at our outpatient clinic. During the study period, 28 patients were considered suitable for LVAD implantation (mean age 63 ± 10.8 years, 92% men, 78% ischaemic, median HF duration 4 years). Clinical stabilization was achieved and maintained in 21 patients (median follow‐up 20 months, range 9–38 months). Compared with baseline evaluation, cardiac index increased from 2.05 (1.73–2.28) to 2.88 (2.63–3.55) L/min/m2, left ventricular end‐diastolic diameter decreased from 65.5 (62.4–66) to 58.3 (53.8–62.5) mm, and maximal oxygen consumption increased from 10.1 (9.2–11.3) to 16.1 (15.3–19) mL/kg/min. Three patients died and only four ultimately required LVAD implantation.

Conclusions

Notwithstanding the small size of our cohort, our results suggest that LVAD implantation could be safely deferred in the majority of LVAD candidates.
Experimental validation, analytical investigation, and design method of tuned mass damper‐clutching inerter for robust control of structures
Authors: Wang Jingjing , Zheng Yuqiang
Published: November 2022

Inerters have significantly uplifted the cost‐effectiveness of structural control technologies. A recently proposed tuned mass damper‐clutching inerter (TMDCI) takes advantage of both mass amplification effect and energy absorption capacity of inerter which is more effective and practical than its predecessors. However, the existing study only provided numerical demonstrations while experimental evidence and analytical explanation are still lacking for in‐depth understanding of the dynamic properties and working principles of TMDCIs. In this study, the mathematical descriptions of TMDCIs are first developed and experimentally validated on a three‐story structure. The validated model is then used to analyze the influences of inerter arrangement and total inertance in inerter‐enhanced devices. With an appropriate inerter arrangement and inertance, the TMDCI shows excellent control performance regardless of the changes in the structural frequency. The reason for the strong robustness of TMDCIs is then revealed via analytical investigation of standalone TMDCIs; the harmonically forced steady‐state responses manifest that the TMDCI can be linearized as equivalent tuned mass damper‐inerters with variable parameters whose natural frequency increases with the increase of excitation frequency. Based on the analytical findings, a design method with robustness consideration is subsequently proposed and draws satisfactory TMDCI designs for both single‐degree‐of‐freedom and multi‐degree‐of‐freedom structures. The designed TMDCI outperforms the comparable devices for both impulsive and seismic response mitigation. The study provides analytical insight into the control capacity of TMDCIs and lays the groundwork for practical design of TMDCIs as an effective and robust control strategy for engineering structures.
RETRACTED: Artificial intelligence framework‐based ultra‐lightweight communication protocol for prediction of attacks in Internet of Things environment
Authors: Jammula Mounika , Vakamulla Venkata Mani , Kondoju Sai Krishna
Published: November 2022

The Internet of Things is an enhanced intelligent infrastructure that is created through the use of a number of different devices that are capable of self‐organization. Data privacy and protection are the primary problems brought up by this enormous network. In addition, the devices in the network with constrained resources are battery‐powered, thus they only have a limited capacity to store resources internally. Because of this, it is vital to discover solutions that are more resource‐optimized and connected to security in order to solve the issues that were caused by the network. The devices are being forced to maintain more complicated cryptographic algorithms for higher security. Therefore, this article proposes an integrated communication protocol that requires only symmetric key‐based cryptography with a deep learning convolutional neural network, which is employed for predicting the normal and attacked data from the input requested data. Here, the logical map is used to produce the symmetric keys due to its resistance against the attacks of key reset and device capture. This integrated model provides an ultra‐lightweight communication protocol with reduced attack detection time while enhancing the attack detection parameters such as precision, accuracy, F1‐score, and recall.
Differences in functional connectivity distribution after transcranial direct‐current stimulation: A connectivity density point of view
Authors: Tang Bohao , Zhao Yi , Venkataraman Archana , Tsapkini Kyrana , Lindquist Martin A. , Pekar James , Caffo Brian
Published: November 2022

In this manuscript, we consider the problem of relating functional connectivity measurements viewed as statistical distributions to outcomes. We demonstrate the utility of using the distribution of connectivity on a study of resting‐state functional magnetic resonance imaging association with an intervention. The method uses the estimated density of connectivity between nodes of interest as a functional covariate. Moreover, we demonstrate the utility of the procedure in an instance where connectivity is naturally considered an outcome by reversing the predictor/response relationship using case/control methodology. The method utilizes the density quantile, the density evaluated at empirical quantiles, instead of the empirical density directly. This improved the performance of the method by highlighting tail behavior, though we emphasize that by being flexible and non‐parametric, the technique can detect effects related to the central portion of the density. To demonstrate the method in an application, we consider 47 primary progressive aphasia patients with various levels of language abilities. These patients were randomly assigned to two treatment arms, transcranial direct‐current stimulation and language therapy versus sham (language therapy only), in a clinical trial. We use the method to analyze the effect of direct stimulation on functional connectivity. As such, we estimate the density of correlations among the regions of interest and study the difference in the density post‐intervention between treatment arms. We discover that it is the tail of the density, rather than the mean or lower order moments of the distribution, that demonstrates a significant impact in the classification. The new approach has several benefits. Among them, it drastically reduces the number of multiple comparisons compared with edge‐wise analysis. In addition, it allows for the investigation of the impact of functional connectivity on the outcomes where the connectivity is not geometrically localized.
Clinical efficacy of synbiotics in children with allergic rhinitis: An observational cohort study from a private medical center in Peru
Authors: Galvan Calle Cesar A. , Díaz Vásquez Cecilia , Muñoz Leon Ricardo , Matos Benavides Edgar E. , Verde Leon Alejandra V.
Published: November 2022

Background

Probiotics in allergic rhinitis (AR) have shown improvement in clinical and quality of life scores, whereas the role of synbiotics in the treatment of AR has been poorly investigated. The purpose of this study was to evaluate the clinical efficacy of synbiotics in children with AR.

Methods

An observational, prospective cohort study of pediatric outpatients with AR from a private medical center in Peru (2021) was conducted. At baseline, patients who were prescribed synbiotics during routine and those who were not (controls) recruited and followed up on Days 30, 60, and 90 of follow‐up. Clinical efficacy was assessed with differences in Visual Analogous Scale (VAS), Total Nasal Symptom Score (TNSS), Rhinitis Control Assessment Test (RCAT), and the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) scores between groups at follow‐up. Mean differences ± standard deviation (SD) and 95% confidence intervals (95% CI) are reported.

Results

Two hundred and fifteen participants were analyzed. Compared to controls (n = 115), those who used synbiotics (n = 100) had significantly lower VAS (mean difference 1.3; 95% CI: 0.8–1.8), TNSS (mean difference 1.1; 95% CI: 0.5–1.7) and higher RCAT scores and PRQLQ scores (mean difference 2.2; 95% CI: −3.3 to −1.2) and (mean difference 7.0; 95% CI: 3.1–10.9), respectively, at Day 90 of follow‐up

Conclusions

This paper reports significant improvement in clinical (VAS, RCAT, TNSS) and quality of life (PRQLQ) scores of small and large sizes, respectively. These preliminary findings support the need of future trials to assess the role of synbiotics in children with AR.
The modulation of macrophage subsets in celiac disease pathogenesis
Authors: Molaaghaee‐Rouzbahani Sara , Asri Nastaran , Jahani‐Sherafat Somayeh , Amani Davar , Masotti Andrea , Baghaei Kaveh , Yadegar Abbas , Mirjalali Hamed , Rostami‐Nejad Mohammad
Published: November 2022

Background

So far, limited studies have focused on the role of Macrophages (MQs) in the development or progression of celiac disease (CD). Researchers believe that increasing knowledge about the function of MQs in inflammatory disorders plays a critical role in finding a new treatment for these kinds of diseases.

Main body

CD is a permanent autoimmune intestinal disorder triggered by gluten exposure in predisposed individuals. This disorder happens due to the loss of intestinal epithelial barrier integrity characterized by dysregulated innate and adaptive immune responses. MQs are known as key players of the innate immune system that link innate and adaptive immunity. MQs of human intestinal lamina propria participate in maintaining tissue homeostasis, and also intestinal inflammation development. Previous studies suggested that gliadin triggers a proinflammatory phenotype (M1 MQ) in human primary MQs. Moreover, M2‐related immunosuppressive mediators are also present in CD. In fact, CD patients present an impaired transition from pro‐inflammatory to anti‐inflammatory responses due to inappropriate responses to gliadin peptides.

Conclusion

The M1/M2 MQs polarization balancing regulators can be considered novel therapeutic targets for celiac disease.
The effect of the US dollar exchange rate on oil prices: An oil financialization perspective
Authors: Wang Panpan , Liu Xiaoxing , Ho Tsungwu , Li Yishi
Published: November 2022

This study investigates the regime‐specific relationship between the USD exchange rate and oil prices. We embed the threshold variables of structural breaks and oil financialization into the VAR model of the dollar–oil relationship. Using daily data from 1983 to 2022, we find that a marked structural change in the dollar–oil relation exists in 2001 and that deepening oil financialization drives the structural change, making the portfolio effect the dominant effect of the dollar on oil prices. After 2001, the dollar negatively affects oil prices in both the long and short run. Furthermore, our threshold regression based on the investor self‐adaptive expectation model shows that investor expectations significantly affect the dollar–oil relationship under oil financialization. A sharp increase in USD exchange rate volatility would strengthen investors' unilateral expectation of the trend of the USD exchange rate, which further enhances the portfolio effect, resulting in an even stronger negative effect of the dollar on oil prices.
2D MXenes for controlled releases of therapeutic proteins
Authors: Seitak Aibobek , Shanti Aya , Al Adem Kenana , Farid Nouran , Luo Shaohong , Iskandarov Javad , Karanikolos Georgios N. , Liao Kin , Chan Vincent , Lee Sungmun
Published: November 2022

MXenes belong to a new class of two dimensional (2D) functional nanomaterials, mainly encompassing transition‐metal carbides, nitrides and carbonitrides, with unique physical, chemical, electronic and mechanical properties for various emerging applications across different fields. To date, the potentials of MXenes for biomedical application such as drug delivery have not been thoroughly explored due to the lack of information on their biocompatibility, cytotoxicity and biomolecule‐surface interaction. In this study, we developed novel drug delivery system from MXene for the controlled release of a model therapeutic protein. First, the structural, chemical and morphological properties of as synthesized MXenes were probed with electron microscopy and X‐ray diffraction. Second, the potential cytotoxicity of MXene toward the proliferation and cell morphology of murine macrophages (RAW 264.7) were evaluated with MTT assays and electron microscopy, respectively. Moreover, the drug loading capacities and sustained release capabilities of MXene were assessed in conjunction with machine learning approaches. Our results demonstrated that MXene did not significantly induce cellular toxicity at any concentration below 1 mg/ml which is within the range for effective dose of drug delivery vehicle. Most importantly, MXene was efficiently loaded with FITC‐catalase for subsequently achieving controlled release under different pHs. The release profiles of catalase from MXene showed higher initial rate under basic buffer (pH 9) compared to that in physiological (pH 7.4) and acidic buffers (pH 2). Taken together, the results of this study lead to a fundamental advancement toward the use of MXene as a nanocarrier for therapeutic proteins in drug delivery applications.
Protein Kinase G2 Is Essential for Skeletal Homeostasis and Adaptation to Mechanical Loading in Male but Not Female Mice
Authors: Kalyanaraman Hema , Pal China Shyamsundar , Cabriales Justin A. , Moininazeri Jafar , Casteel Darren E. , Garcia Julian J. , Wong Van W. , Chen Albert , Sah Robert L. , Boss Gerry R. , Pilz Renate B.
Published: November 2022

We previously showed that the NO/cGMP/protein kinase G (PKG) signaling pathway positively regulates osteoblast proliferation, differentiation, and survival in vitro, and that cGMP-elevating agents have bone-anabolic effects in mice. Here, we generated mice with an osteoblast-specific (OB) knockout (KO) of type 2 PKG (gene name Prkg2) using a Col1a1(2.3 kb)-Cre driver. Compared to wild type (WT) littermates, 8-week-old male OB Prkg2-KO mice had fewer osteoblasts, reduced bone formation rates, and lower trabecular and cortical bone volumes. Female OB Prkg2-KO littermates showed no bone abnormalities, despite the same degree of PKG2 deficiency in bone. Expression of osteoblast differentiation- and Wnt/β-catenin-related genes was lower in primary osteoblasts and bones of male KO but not female KO mice compared to WT littermates. Osteoclast parameters were unaffected in both sexes. Since PKG2 is part of a mechano-sensitive complex in osteoblast membranes, we examined its role during mechanical loading. Cyclical compression of the tibia increased cortical thickness and induced mechanosensitive and Wnt/β-catenin-related genes to a similar extent in male and female WT mice and female OB Prkg2-KO mice, but loading had a minimal effect in male KO mice. We conclude that PKG2 drives bone acquisition and adaptation to mechanical loading via the Wnt/β-catenin pathway in male mice. The striking sexual dimorphism of OB Prkg2-KO mice suggests that current U.S. Food and Drug Administration-approved cGMP-elevating agents may represent novel effective treatment options for male osteoporosis. © 2022 American Society for Bone and Mineral Research (ASBMR).
Knockdown of hsa_circ_0043691 restrains the progression of gastric cancer by decoying miR‐1294 to target pre‐leukemia transcription factor 3
Authors: Wu Jing , Gong Pan , Jiang Zhiyong
Published: November 2022

Background

Circular RNAs (circRNAs) have been found to render pivotal effects in gastric cancer (GC). However, the effect of hsa_circ_0043691 in GC still needs to be further unveiled.

Methods

The contents of hsa_circ_0043691, miR‐1294, and pre‐leukemia transcription factor 3 (PBX3) were examined using qRT‐PCR or Western blot assay. In vitro colony formation, transwell, wound healing, flow cytometry, tube formation assays, glutaminolysis corresponding kit and in vivo Xenograft mice model were utilized to evaluate cell functions. The relationship between miR‐1294 and hsa_circ_0043691 or PBX3 was further verified.

Results

The levels of hsa_circ_0043691 and PBX3 were upregulated, whereas miR‐1294 expression was diminished in GC tissues and cells. Hsa_circ_0043691 deficiency significantly inhibited GC cell progression and glutaminolysis metabolism. Mechanistically, hsa_circ_0043691 was directly bound to miR‐1294 to modulate PBX3 expression. Besides, silencing of hsa_circ_0043691 impeded tumor growth in vivo.

Conclusion

Hsa_circ_0043691 knockdown repressed GC malignant phenotypes by miR‐1294/PBX3 axis, which exhibited a novel therapeutic target for GC treatment.
Glucose and mannose analogs inhibit KSHV replication by blocking N‐glycosylation and inducing the unfolded protein response
Authors: Schlesinger Mariana , McDonald Christian , Ahuja Anuj , Alvarez Canete Carolina Alejandra , Nuñez del Prado Zelmira , Naipauer Julian , Lampidis Theodore , Mesri Enrique A.
Published: November 2022

Kaposi's sarcoma‐associated herpesvirus (KSHV) is the etiological agent for Kaposi's sarcoma (KS), an HIV/AIDS‐associated malignancy. Effective treatments against KS remain to be developed. The sugar analog 2‐deoxy‐
d‐glucose (2‐DG) is an anticancer agent that is well‐tolerated and safe in patients and was recently demonstrated to be a potent antiviral, including KSHV and severe acute respiratory syndrome coronavirus 2. Because 2‐DG inhibits glycolysis and N‐glycosylation, identifying its molecular targets is challenging. Here we compare the antiviral effect of 2‐DG with 2‐fluoro‐deoxy‐
d‐glucose, a glycolysis inhibitor, and 2‐deoxy‐fluoro‐
d‐mannose (2‐DFM), a specific N‐glycosylation inhibitor. At doses similar to those clinically achievable with 2‐DG, the three drugs impair KSHV replication and virion production in iSLK.219 cells via downregulation of viral structural glycoprotein expression (K8.1 and gB), being 2‐DFM the most potent KSHV inhibitor. Consistently with the higher potency of 2‐DFM, we found that
d‐mannose rescues KSHV glycoprotein synthesis and virus production, indicating that inhibition of N‐glycosylation is the main antiviral target using
d‐mannose competition experiments. Suppression of N‐glycosylation by the sugar drugs triggers ER stress. It activates the host unfolded protein response (UPR), counteracting KSHV‐induced inhibition of the protein kinase R‐like endoplasmic reticulum kinase branch, particularly activating transcription factor 4 and C/EBP homologous protein expression. Finally, we demonstrate that sugar analogs induce autophagy (a prosurvival mechanism) and, thus, inhibit viral replication playing a protective role against KSHV‐induced cell death, further supporting their direct antiviral effect and potential therapeutic use. Our work identifies inhibition of N‐glycosylation leading to ER stress and UPR as an antienveloped virus target and sugar analogs such as 2‐DG and the newly identified 2‐DFM as antiviral drugs.
Gender and Ethnic Diversity in Academic Facial Plastic Surgery
Authors: Chou David W. , Layfield Eleanor , Prasad Karthik , Shih Charles , Brandstetter Kathleyn
Published: November 2022

Objective

Characterize academic facial plastic surgeons by demographics, time in practice, academic productivity, and faculty position.

Study Type

Cross‐sectional study.

Methods

Facial plastic surgery faculty in US otolaryngology residencies with a title of assistant professor, associate professor, or professor were identified. Demographics and academic data were obtained from public profiles and Scopus.

Results

One hundred sixty‐eight surgeons were identified. Females comprised 25.6%. Most surgeons were White (69.6%), followed by Asian (25%), Hispanic (3.6%), and Black (1.8%). Mean h‐index was similar between sexes when controlling for years in practice (1.13 vs. 1.14, p = 0.575). Female representation was greater among early‐career surgeons (41%) than among mid‐ or late‐career surgeons (24% and 13%, respectively) (p = 0.006). The correlation of years in practice with academic title was similar between sexes. There was no difference in h‐index (p = 0.384) or distribution of academic positions (p = 0.658) between White and non‐White surgeons. There was no statistical difference in full professorship (p = 1.0) or research productivity (p = 0.974) between late‐career White and non‐White academic facial plastic surgeons. There was no statistical difference in promotion from assistant professorship (p = 0.506) or research productivity (p = 0.857) between White and non‐White surgeons in practice for over 5 years.

Conclusion

Female representation in academic facial plastic surgery is low, though greater gender parity among younger surgeons suggests an improving trend. Hispanic and Black surgeons remain significantly underrepresented in the field. Although increased diversity is needed in academic facial plastic surgery, established minority surgeons have experienced similar research productivity and advancement through academic ranks as their majority counterparts.

Level of Evidence

N/A Laryngoscope, 133:1869–1874, 2023
Twelve years of assessing the quality of preimplantation genetic testing for monogenic disorders
Authors: Deans Zandra C. , Biricik Anil , De Rycke Martine , Harton Gary L. , Hornak Miroslav , Khawaja Farrah , Moutou Céline , Traeger‐Synodinos Jan , Renwick Pamela
Published: November 2022

Objective

Genomics Quality Assessment has provided external quality assessments (EQAs) for preimplantation genetic testing (PGT) for 12 years for eight monogenic diseases to identify sub‐optimal PGT strategies, testing and reporting of results, which can be shared with the genomics community to aid optimised standards of PGT services for couples.

Method

The EQAs were provided in two stages to mimic end‐to‐end protocols. Stage 1 involved DNA feasibility testing of a couple undergoing PGT and affected proband. Participants were required to report genotyping results and outline their embryo testing strategy. Lymphoblasts were distributed for mock embryo testing for stage 2. Submitted clinical reports and haplotyping results were assessed against peer‐ratified criteria. Performance was monitored to identify poor performance.

Results

The most common testing methodology was short tandem repeat linkage analysis (59%); however, the adoption of single nucleotide polymorphism‐based platforms was observed and a move from blastomere to trophectoderm testing. There was a variation in testing strategies, assigning marker informativity and understanding test limitations, some clinically unsafe. Critical errors were reported for genotyping and interpretation.

Conclusion

EQA provides an overview of the standard of preimplantation genetic testing‐M clinical testing and identifies areas of improvement for accurate detection of high‐risk embryos.
Fetal cerebral ventriculomegaly: What do we tell the prospective parents?
Authors: Giorgione Veronica , Haratz Karina Krajden , Constantini Shlomi , Birnbaum Roee , Malinger Gustavo
Published: November 2022

Fetal cerebral ventriculomegaly is a relatively common finding, observed during approximately 1% of obstetric ultrasounds. In the second and third trimester, mild (≥10 mm) and severe ventriculomegaly (≥15 mm) are defined according to the measurement of distal lateral ventricles that is included in the routine sonographic examination of central nervous system. A detailed neurosonography and anatomy ultrasound should be performed to detect other associated anomalies in the central nervous system and in other systems, respectively. Fetal MRI might be useful when neurosonography is unavailable or suboptimal. The risk of chromosomal and non‐chromosomal genetic disorders associated with ventriculomegaly is high, therefore invasive genetic testing, including microarray, is recommended. Screening for prenatal infections, in particular cytomegalovirus and toxoplasmosis, should also be carried out at diagnosis. The prognosis is determined by the severity of ventriculomegaly and/or by the presence of co‐existing abnormalities. Fetal ventriculoamniotic shunting in progressive isolated severe ventriculomegaly is an experimental procedure. After delivery, ventricular‐peritoneal shunting or ventriculostomy are the two available options to treat hydrocephalus in specific conditions with similar long‐term outcomes. A multidisciplinary fetal neurology team, including perinatologists, geneticists, pediatric neurologists, neuroradiologists and neurosurgeons, can provide parents with the most thorough prenatal counseling. This review outlines the latest evidence on diagnosis and management of pregnancies complicated by fetal cerebral ventriculomegaly.
Boron‐doped polysilicon using spin‐on doping for high‐efficiency both‐side passivating contact silicon solar cells
Authors: Park HyunJung , Kim Jinsol , Choi Dongjin , Lee Sang‐Won , Kang Dongkyun , Lee Hae‐Seok , Kim Donghwan , Kim Munho , Kang Yoonmook
Published: November 2022

This study focuses on boron‐doped p+polysilicon (poly‐Si) passivating contacts using spin‐on doping (SOD). Experimental conditions, including annealing conditions, SOD concentration, and poly‐Si thickness, were controlled to improve passivation. Based on the analysis results, the passivation quality mainly changes with indiffusion and doping concentration, causing Auger recombination and field effects. Meanwhile, grain size also influences the passivation quality but showed marginal characteristics. Through further optimization using an etch back and diffusion barrier, the efficiency of the flat reference solar cell was improved to 17.5% with an open‐circuit voltage of 695 mV using a p+ poly‐Si contact emitter, the highest reported efficiency using SOD on saw‐damage‐etched surfaces. This study includes a detailed analysis of SOD p+ poly‐Si and shows promising results with potential for application in tandem devices. Furthermore, the cell efficiency is expected to increase by controlling the doping profile and application of textured surfaces, selective emitters, and forming gas annealing (FGA).
Registration of Arkot 1005, Arkot 1015, and Arkot 1019 cotton germplasm lines
Authors: Bourland Fred , Jones Don
Published: November 2022

Arkot 1005 (Reg. no. GP‐1127, PI 700852), Arkot 1015 (Reg. no. GP‐1128, PI 700853), and Arkot 1019 (Reg. no. GP‐1129, PI 700854) are conventional cotton (Gossypium hirsutum L.) germplasm lines released by the Arkansas Agricultural Experiment Station in April 2022. The lines were compared with UA48 and UA222 (check cultivars) in replicated field tests at four Arkansas sites over 5 yr. Over these tests, lint yields of the three lines did not differ from each other and were greater than UA48. Lint yield of Arkot 1015 was greater than UA222, while lint yields of Arkot 1005 and Arkot 1019 were equal to UA222. Performance in regional tests indicates that the lines have wide adaptation. The lint yields of Arkot 1015 and Arkot 1019 were attributed to producing more (and smaller) seed per area and less lint per seed (lint index) than UA222. Arkot 1005 produced higher lint index than the other two lines and the two check cultivars. Seed per area for Arkot 1005 was higher than UA48, equal to UA222, and lower than Arkot 1015 and Arkot 1019. Leaf pubescence, stem pubescence, and bract trichome density of the three lines were intermediate between UA222 and UA48. All three lines displayed high resistance to bacterial blight and were similar to UA222 and UA48 in their response to other diseases. Arkot 1015 was more resistant to tarnished plant bug (TPB) than Arkot 1005, Arkot 1019, and UA48, but all were more susceptible to TPB than UA222. Compared with the other lines and check cultivars, Arkot 1005 and Arkot 1019 displayed higher and lower, respectively, resistance to seed deterioration. Fiber quality of Arkot 1019 was superior to UA48, UA222, and the other lines. Fiber quality of Arkot 1005 and Arkot 1015 was superior to UA222.
The association between pre‐existing asthma and reduced risk of death among children and adolescents hospitalized with COVID‐19 in Brazil
Authors: Oliveira Maria C. L. , Colosimo Enrico A. , Vasconcelos Mariana A. , Martelli‐Júnior Hercílio , Mak Robert H. , Silva Ludmila R. , Pinhati Clara C. , Simões e Silva Ana C. , Oliveira Eduardo A.
Published: November 2022

Objective

There have been conflicting reports on the relationship between asthma and COVID‐19 severity. This study aimed to compare the risk of death among children with asthma and healthy peers hospitalized due to COVID‐19.

Methods

We carried out an analysis of all pediatric patients 2–19 years of age with asthma and COVID‐19 registered in Influenza Epidemiological Surveillance Information System‐Gripe, a Brazilian nationwide surveillance database, between February 2020 and March 2022. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk using the cumulative incidence function.

Results

Among 30,405 hospitalized children with COVID‐19, 21,340 (70.2%) had no comorbidities, 6444 (21.2%) had comorbidities other than asthma, 2165 (7.1%) had asthma, and 465 (1.5%) had asthma with other comorbidities. The estimated probability of a fatal outcome for each group was 4.1%, 14.9%, 2.1%, and 10.7%, respectively. After adjustment, children with asthma had a 60% reduction in the hazard of death than healthy peers (hazard ratio [HR] = 0.39, 95% confidence interval [CI], 0.29–0.53, p < 0.0001). Among children with asthma and no other comorbidities, two covariates were independently associated with in‐hospital mortality, age ≥12 years, HR = 4.0, 95% CI, 2.5–6.4), and low oxygen saturation at admission (HR = 2.3, 95% CI, 1.4–3.2).

Conclusion

Children with asthma and no comorbidities had a lower risk of death compared with healthy peers after controlling for clinical and demographic confounding factors.
Quantifying the effects of lossy compression on energies calculated from molecular dynamics trajectories
Authors: Roe Daniel R. , Brooks Bernard R.
Published: November 2022

Molecular dynamics (MD) simulations are now able to routinely reach timescales of microseconds and beyond. This has led to a corresponding increase in the amount of MD trajectory data that needs to be stored, particularly when those trajectories contain explicit solvent molecules. As such, it is desirable to be able to compress trajectory data while still retaining as much of the original information as possible. In this work, we describe compressing MD trajectory data using the NetCDF4/HDF5 file format, making use of quantization of the original positions to achieve better compression ratios. We also analyze the affect this has on both the resulting positions and the energies calculated from post‐processing these trajectories, and recommend an optimal level of quantization. Overall we find the NetCDF4/HDF5 format to be an excellent choice for storing MD trajectory data in terms of speed, compressibility, and versatility.
Differential responses to taxanes and PARP inhibitors in ATM‐ versus BRCA2‐mutated metastatic castrate‐resistant prostate cancer
Authors: Su Christopher T. , Nizialek Emily , Berchuck Jacob E. , Vlachostergios Panagiotis J. , Ashkar Ryan , Sokolova Alexandra , Barata Pedro C. , Aggarwal Rahul R. , McKay Rana R. , Agarwal Neeraj , McClure Heather M. , Nafissi Nellie , Bryce Alan H. , Sartor Oliver , Sayegh Nicolas , Cheng Heather H. , Adra Nabil , Sternberg Cora N. , Taplin Mary‐Ellen , Cieslik Marcin , Alva Ajjai S. , Antonarakis Emmanuel S.
Published: November 2022

Background

PARP (poly(ADP‐ribose) polymerase) inhibitors (PARPi) are now standard of care in metastatic castrate‐resistant prostate cancer (mCRPC) patients with select mutations in DNA damage repair (DDR) pathways, but patients with ATM‐ and BRCA2 mutations may respond differently to PARPi. We hypothesized that differences may also exist in response to taxanes, which may inform treatment sequencing decisions.

Methods

mCRPC patients (N = 158) with deleterious ATM or BRCA2 mutations who received taxanes, PARPi, or both were retrospectively identified from 11 US academic centers. Demographic, treatment, and survival data were collected. Kaplan−Meier analyses were performed and Cox hazard ratios (HR) were calculated for progression‐free survival (PFS) as well as overall survival (OS), from time of first taxane or PARPi therapy.

Results

Fifty‐eight patients with ATM mutations and 100 with BRCA2 mutations were identified. Fourty‐four (76%) patients with ATM mutations received taxane only or taxane before PARPi, while 14 (24%) received PARPi only or PARPi before taxane. Patients with ATM mutations had longer PFS when taxane was given first versus PARPi given first (HR: 0.74 [95% confidence interval [CI]: 0.37−1.50]; p = 0.40). Similarly, OS was longer in patients with ATM mutations who received taxane first (HR: 0.56 [CI: 0.20−1.54]; p = 0.26). Among patients with BRCA2 mutations, 51 (51%) received taxane first and 49 (49%) received PARPi first. In contrast, patients with BRCA2 mutations had longer PFS when PARPi was given first versus taxane given first (HR: 0.85 [CI: 0.54−1.35]; p = 0.49). Similarly, OS was longer in patients with BRCA2 mutations who received PARPi first (HR: 0.75 [CI: 0.41−1.37]; p = 0.35).

Conclusions

Our retrospective data suggest differential response between ATM and BRCA2 mutated prostate cancers in terms of response to PARPi and to taxane chemotherapy. When considering the sequence of PARPi versus taxane chemotherapy for mCRPC with DDR mutations, ATM, and BRCA2 mutation status may be helpful in guiding choice of initial therapy.