bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Kidney Stones in Renal Pelvis Flow
Authors: Constante-Amores C. R. , Kahouadji L. , Williams J. G. , Turney B. W. , Shin S. , Chergui J. , Juric D. , Moulton D. E. , Waters S. L.
Published: December 2022

Ureteroscopy is a commonly performed medical procedure to treat stones in the kidney and ureter using a ureteroscope. Throughout the procedure, saline is irrigated through the scope to aid visibility and wash-out debris from stone fragmentation. The key challenge that this research addresses is to build a fundamental understanding of the interaction between the kidney stones/stone fragments and the flow dynamics in the renal pelvis flow. We examine the time-dependent flow dynamics inside an idealized renal pelvis in the context of a surgical procedure for kidney stone removal. Here, we examine the time-dependent evolution of these vortical flow structures in three dimensions, and incorporate the presence of rigid kidney stones. We perform direct numerical simulations, solving the transient Navier–Stokes equations in a spherical domain. Our numerical predictions for the flow dynamics in the absence of stones are validated with available experimental and numerical data, and the governing parameters and flow regimes are chosen carefully in order to satisfy several clinical constraints. The results shed light on the crucial role of flow circulation in the renal cavity and its effect on the trajectories of rigid stones. We demonstrate that stones can either be washed out of the cavity along with the fluid, or be trapped in the cavity via their interaction with vortical flow structures. Additionally, we study the effect of multiple stones in the flow field within the cavity in terms of the kinetic energy, entrapped fluid volume, and the clearance rate of a passive tracer modeled via an advection–diffusion equation. We demonstrate that the flow in the presence of stones features a higher vorticity production within the cavity compared with the stone-free cases.
Machine Learning Metamodel of a Computationally Intense LOCA Code
Authors: Conner Landon A. , Worrell Clarence L. , Liao Jun , Spring James P. , Karimi Reza A. , Marquardt Jeremy S. , Wieder Joseph D.
Published: December 2022

The nuclear power industry is increasingly identifying applications of machine learning to reduce design, engineering, manufacturing, and operational costs. In some cases, applications have been deployed and are providing value, particularly in data rich manufacturing areas. In this paper, we use machine learning to develop metamodel approximations of a computationally intense safety analysis code used to simulate a postulated loss-of-coolant accident (LOCA). Accurate metamodels run at a fraction of the computational cost (milliseconds) compared to the LOCA analysis code. Metamodels can therefore support applications requiring a high volume of runs such as optimization, uncertainty analysis, and probabilistic decision analysis, which would otherwise not be possible using the computationally intense code. In this study, training data is first generated by running the safety analysis code over a design of experiment. Exploratory data analysis is then performed followed by an initial fitting of several model forms, including neighbor-based models, tree-based models, support vector machines, and artificial neural networks. A neural network is selected as the most promising candidate and hyperparameter optimization using a genetic algorithm is performed. Finally, the resulting model, its potential applications, and areas for further research are discussed.
Multi-modal thermoacoustic instability suppression via locally resonant and Bragg bandgaps
Authors: Liu Yang , Cheng Li , Du Jingtao
Published: December 2022

Thermoacoustic instability is a common occurrence in combustors, yielding self-sustained oscillations and causing potential risk, such as severe structural damage. In this paper, modal instability suppression inside a duct is studied using periodically arranged membranes within the framework of a linear heat release n-τ model embedded into a fully coupled energy-based model. The periodic arrangement of the membranes along the duct sidewall enables locally resonant and Bragg scattering bandgaps, shown to be conducive for the stabilization of unstable thermoacoustic modes. Eigen-modes are classified into different groups, which call for specific control actions in relation with the bandgap frequencies. While multi-modal instability control of low-order modes can be achieved through the tuning of the resonant bandgaps, the densely packed modal cluster, regrouping modes featuring similar mode shapes, requires proper adjustment of the flame position for avoiding modal instability. Compared with the Bragg bandgaps, locally resonant bandgaps, which should be formed near the unstable modes even without stringent periodicity, are shown to play a decisive role in the control process. Meanwhile, strict periodicity is not necessary for the proposed control strategy, showing the practicability of the proposed control strategy. The study shows a promising route to achieve simultaneous suppression of multi-modal instability.
Effect of Elite Sport on Physical Activity Practice in the General Population: A Systematic Review
Authors: Lion Alexis , Vuillemin Anne , Léon Florian , Delagardelle Charles , van Hoye Aurélie
Published: December 2022

Background: Our study investigated the effect of elite sport on physical activity (PA) practice in the general population. Methods: Structured Boolean searches were conducted across 5 electronic databases (PubMed, JSTOR, Web of Science, SPORTDiscus, and PsycInfo) from January 2000 to August 2021. Peer-reviewed studies in English were included if the effects of hosting elite sport events, elite sport success, and elite sport role modeling on PA/sport practice in the general population were measured. Results: We identified 12,563 articles and included 36 articles. Most studies investigated the effect of hosting elite sport events (n = 27), followed by elite sport success (n = 16) and elite sport role modeling (n = 3). Most studies did not observe a positive effect of hosting elite sport events, elite sport success, or elite sport role modeling on PA/sport practice in the general population. No evidence of a lagged effect of elite sport was observed. No evidence of elite sport effects was observed according to age range and geographical scale. Conclusion: There is no evidence supporting the effect of elite sport in increasing PA or sport participation in the general population. Decision makers and policymakers should be aware of this and invest in strategies such as those recommended by the World Health Organization.
Stress signaling boosts interferon-induced gene transcription in macrophages
Authors: Boccuni Laura , Podgorschek Elke , Schmiedeberg Moritz , Platanitis Ekaterini , Traxler Peter , Fischer Philipp , Schirripa Alessia , Novoszel Philipp , Nebreda Angel R. , Arthur J. Simon C. , Fortelny Nikolaus , Farlik Matthias , Sexl Veronika , Bock Christoph , Sibilia Maria , Kovarik Pavel , Müller Mathias , Decker Thomas
Published: December 2022

Promoters of antimicrobial genes function as logic boards, integrating signals of innate immune responses. One such set of genes is stimulated by interferon (IFN) signaling, and the expression of these genes [IFN-stimulated genes (ISGs)] can be further modulated by cell stress–induced pathways. Here, we investigated the global effect of stress-induced p38 mitogen-activated protein kinase (MAPK) signaling on the response of macrophages to IFN. In response to cell stress that coincided with IFN exposure, the p38 MAPK-activated transcription factors CREB and c-Jun, in addition to the IFN-activated STAT family of transcription factors, bound to ISGs. In addition, p38 MAPK signaling induced activating histone modifications at the loci of ISGs and stimulated nuclear translocation of the CREB coactivator CRTC3. These actions synergistically enhanced ISG expression. Disrupting this synergy with p38 MAPK inhibitors improved the viability of macrophages infected with
Listeria monocytogenes
. Our findings uncover a mechanism of transcriptional synergism and highlight the biological consequences of coincident stress-induced p38 MAPK and IFN-stimulated signal transduction.
Longitudinal Study of the Effects of Flammulina velutipes Stipe Wastes on the Cecal Microbiota of Laying Hens
Authors: Wei Jiali , Xiao Huanwei , Wei Yingbo , Nguepi Tsopmejio Ivan Stève , Sun Chang , Wu Haoyuan , Jin Zhouyu , Song Hui
Published: December 2022

Dietary fiber is popularly used in poultry farming to improve host health and metabolism. Microbial composition is known to be influenced by dietary fiber use, although the exact FVW-induced changes remain unclear.
Early riser specific immune cell response by delayed-type hypersensitivity in a kidney transplant patient vaccinated against COVID-19
Authors: Barrios Yvelise , Alava-Cruz Cristina , Marrero-Miranda Domingo , Matheu Victor
Published: December 2022

We present a female kidney transplant patient under conventional immunosuppression therapy. Her humoral immunity study (anti-spike-specific antibodies) was negative after the initial regimen and the third dose of vaccination against COVID-19. The specific ex vivo cellular immune study against spike of SARS-CoV-2 by interferon gamma release assay (IGRA) also remained at non-response levels at different time points despite an optimal non-specific cell immune response assessment. However, the cellular immunity test by delayed-type hypersensitivity (DTH) with spike of SARS-CoV-2 was always positive since the vaccination scheme began. Only after COVID-19 infection has there been a seroconversion of the patient’s antibody tests along with IGRA positivity. The use of DTH test to measure the immune response could be a better and earlier parameter of the actual immune status that helps us to predict the immune response in real life. Hybrid immunity combining vaccine and natural infection could be a stronger stimulator of the specific global immune response.
Occupational exposure to respirable crystalline silica and acute myocardial infarction among men and women in Sweden
Authors: Wiebert Pernilla , Andersson Tomas , Feychting Maria , Sjögren Bengt , Plato Nils , Gustavsson Per
Published: December 2022

Objectives

Occupational exposure to respirable crystalline silica (RCS) is common. The study aimed to assess the risk for acute myocardial infarction (AMI) after long-term exposure to RCS and to explore differences in risk between men and women.

Methods

The cohort included all manual workers identified from the Swedish National Census in 1980 using data on job titles and demography altogether from five censuses from 1960 to 1990, in total 605 246 men and 480 607 women. Information on AMI was obtained from nationwide registers from 1992 to 2006. Exposure to RCS was assessed with a job-exposure matrix. HRs and 95% CIs were estimated by Cox regression, adjusted for age, socioeconomic status and urbanisation index.

Results

Among manual workers ever exposed to RCS, the adjusted risk of AMI was HR 1.29 (95% CI 1.15 to 1.46) in women, and HR 1.02 (95% CI 1.00 to 1.04) in men. In the highest quartile of cumulative exposure, the risk of AMI was HR 1.66 (95% CI 1.27 to 2.18) for women, and HR 1.06 (95% CI 1.03 to 1.10) for men, respectively. The risk of AMI increased with cumulative exposure to RCS both in women (p=0.001) and in men (p=0.016). An interaction analysis showed that the relative risk from exposure to RCS was statistically significantly lower in men than in women at similar exposure levels.

Conclusions

Occupational exposure to RCS was related to the risk of AMI. Women were more sensitive to exposure to RCS than men.
Indigenous-led conservation in the Arctic supports global conservation practices
Authors: Buschman Victoria Q. , Sudlovenick Enooyaq
Published: December 2022

Amid growing recognition for the role of global conservation initiatives in protecting biodiversity and mitigating climate change impacts, the interest in Indigenous-led and Indigenous-centered conservation in the circumpolar Arctic is also on the rise. Through literature and practice, Indigenous communities in the Arctic are shaping the global discourse around conservation approaches, mechanisms, and strategies, and are challenging colonial conceptions of how lands, waters, and species should be used, managed, and protected. Indigenous approaches, mechanisms, and strategies often differ from those found in the global conservation toolbox and rather focus on local priorities, Indigenous knowledge, traditional practices, sovereignty, and self-determination. Direction on how conservation should evolve and overcome challenges and related burdens is best given by Indigenous communities, scholars, organizations, and governments. Valuing Indigenous knowledge and supporting community-level initiatives, strategies, and practices comes with the benefits of understanding, forwarding, and implementing community priorities, needs, and values through attention and focus on funding, Indigenous-led research and management, and mutual mentorship. In addition to benefiting conservation itself, biodiversity research conducted within Indigenous homelands has the opportunity to serve as a model for how regional, national, and international initiatives best engage with Indigenous knowledge, conservation practice, and policy development in the Arctic and beyond.
Spectrum of the S-wave fully-heavy tetraquark states
Authors: Zhang Jie , Wang Jin-Bao , Li Gang , An Chun-Sheng , Deng Cheng-Rong , Xie Ju-Jun
Published: December 2022

In present work, spectrum of the S-wave fully-heavy tetraquark states $$QQ\bar{Q}\bar{Q}$$

Q
Q

Q

¯

Q

¯

($$Q=c,b$$

Q
=
c
,
b

), i.e., $$cc\bar{c}\bar{c}$$

c
c

c

¯

c

¯

, $$bb\bar{b}\bar{b}$$

b
b

b

¯

b

¯

, $$cc\bar{b}\bar{b}$$

c
c

b

¯

b

¯

/$$bb\bar{c}\bar{c}$$

b
b

c

¯

c

¯

, $$bc\bar{c}\bar{c}$$

b
c

c

¯

c

¯

/ $$cc\bar{b}\bar{c}$$

c
c

b

¯

c

¯

, $$bb\bar{c}\bar{b}$$

b
b

c

¯

b

¯

/$$cb\bar{b}\bar{b}$$

c
b

b

¯

b

¯

, and $$bc\bar{b}\bar{c}$$

b
c

b

¯

c

¯

are systematically investigated within a nonrelativistic constituent quark model, in which the instanton-induced and one-gluon-exchange interactions are taken into account as the residual spin-dependent hyperfine interaction. Our results show that the states with $$cc\bar{c}\bar{c}$$

c
c

c

¯

c

¯

and $$bb\bar{b}\bar{b}$$

b
b

b

¯

b

¯

components could be located around 6500 MeV and 19,200 MeV, respectively. Based on our calculations, the new X(6900) state observed by LHCb may be not a ground $$cc\bar{c}\bar{c}$$

c
c

c

¯

c

¯

tetraquark state, while it could be an orbitally or radially excited state of $$cc\bar{c}\bar{c}$$

c
c

c

¯

c

¯

system. On the other hand, the recently reported X(6600) state by CMS and ATLAS can be explained as a ground $$cc\bar{c}\bar{c}$$

c
c

c

¯

c

¯

tetraquark state with spin-parity $$J^{PC} =0^{++}$$

J

PC

=

0

+
+

.
Electrochemical Uric Acid Sensors: Fundamentals and Commercial Status
Authors: Liu Yiqun , Lv Jicheng , Yang Li , Cui Yue
Published: December 2022

An abnormal level of uric acid could lead to serious diseases and complications, such as gout, renal and cardiovascular diseases. Uric acid biosensors have been developed widely for clinical applications. This work would cover the fundamentals and challenges for the development of the uric acid biosensors. The topics include the sensing principles for detecting uric acid, the types of the sensing signals and the signal generation methods, the sensing electrode materials and configurations, the enzymatic and non-enzymatic uric acid sensors, the electrochemiluminescence sensors, the modification approaches for the sensing electrodes, and the commercial status for the sensors. This review explores the fundamentals and practical applications of uric acid biosensors, addresses the current progress and future challenges, and would serve as a resource for the development of uric acid biosensors.
In Vivo Analysis of Extract of Leaves of Mistletoe as a Benalu Duku: Clinical Chemical Value Associated with Histopathology, Liver, Kidneys, and Lethal Dose Determinate
Authors: Lazuardi Mochamad , Chien Chi-Hsien , Jie-Long He , Eka Pramyrtha Hestianah
Published: December 2022

The active compounds from the leaves of Dendrophthoe pentandra L. Miq., also known as, Benalu Duku (in Indonesia), are known to contain progesterone-like compounds (PLCs). This study aims to determine the effect of giving a single dose of PLCs on liver and kidney function in rats and the dose limit that causes the death of experimental animals. The PLCs were analyzed for chemical and physical characterization and compared to a pure standard of progesterone using HPLC, IR spectrometry, thermogravimetry, and NMR. The research was carried out in two sections. In section one, thirty-five healthy adult male rats were divided into six experimental groups and a control group of five rats each. The groups received, respectively, 50 to 75 mg/kg of PLCs (i.p.). The control group was given a 0.5 mL Aqua Pro injection. Alanine aminotransferase, aspartate aminotransferase, creatinine, and blood urea nitrogen were assessed using the clinical chemistry of blood serum analysis. Cell disruptions were analyzed to determine the degeneration effects of PLCs on the liver and kidney in the experimental and control groups. In section two, thirty healthy adult male rats were divided into 6 groups, each group of 5 rats, and injected with PLCs at a dose of 0.9–2.1 g/kg BW, followed by a lethal dose test. The control groups were available for 5 individual rats at 0 g/kg BW of PLCs. Our findings indicated that PLCs have a similarity chemical and physical characterized each other compounds, then the following administration of 50 to 75 mg/kg of PLCs did not affect the parameters of clinical chemistry. Histopathology analysis of the liver and kidney revealed normal subcellular levels in the experimental group, with the nonlethal dose at 0.9 g/kg BW.
Effect of Focus on Form on Vocabulary Acquisition in Computer-Assisted Learning
Authors: Wang Qiang , Zhang Yunfeng , Kolletar-Zhu Kimberly , Xu Xiaoshu , Zhao Liang
Published: December 2022

This study analyzes the impact of focus on form on task-based contextual word acquisition to inform EFL vocabulary learning in a computer-assisted learning environment, with the goal of gaining a better understanding of the cognitive processes behind vocabulary acquisition. A classroom experiment was conducted at a high school in Fujian, China, to investigate two vocabulary acquisition settings for intermediate-level EFL students: maintenance rehearsal and elaborative rehearsal. The results showed that participants in the elaborative rehearsal group outperformed those who recited vocabulary in the maintenance rehearsal condition on the word recall and recognition test. The outcome also indicated that by practicing the input and output of the target words with contextual information in sentence rewriting, the focus-on-form impact of elaborative rehearsal promotes semantic and word form processing.
Wedm Process Optimization for Machining Characteristcis of AISI 52100 Grade Alloy Steel
Authors: Rath Debabrata , Chandra Padhi Pratap , Kumar Sudhir , Singh Inderjeet , Nagaprasad N. , Krishnaraj Ramaswamy
Published: December 2022

The present study deals with one of such investigations, which focuses on optimization of the different machining parameters of WEDM for AISI 52100 grade steel. For this work, a standard design of experimentation (DOE) based on Taguchi L27 orthogonal array (OA) has been used by selecting 6 different input parameters of the WEDM for optimization of two output characteristics (surface roughness (Ra) and dimensional deviation (DD). The results suggest that Pulse on Time (Ton): 1µs, Pulse off time: 18µs; Wire Feed (WF): 12mm/min, Spark Gap Set Voltage (SV): 20V, Wire Tension (WT): 1650, and Servo Feed (SF): 8units) are the best condition for the machining AISI 52100 grade steel as the roughness value (Roughness value: 1.02Ra) and dimensional deviation (Dimensional deviation: 0.02) obtained for these settings came to be least. From the result analysis of the current study, the pulse on time (Ton) was ranked at 1st, spark gap voltage came to be as 2nd rank parameter and pulse off (Toff) time was ranked 3rd, and wire tension was ranked at 4th position which significantly contributed towards the wire-EDM machining of AISI 52100 grade steel. Morphological analysis such as semi electron microscopic (SEM) analysis and 3D surface rendering also supported the observed surface and dimensional behaviour.
Continuous Monitoring Analysis of Rice Quality in Southern China Based on Random Forest
Authors: Lu Lin , Zeng Bo , Yang Shihua , Chen Mingxue , Yu Yonghong
Published: December 2022

Rice quality has received more attention, so monitoring and analysis are of great significance to rice quality. General quality indexes of rice in southern China from 2011 to 2020 were determined, including processing quality (brown rice yield, milled rice recovery, head rice yield), appearance quality (grain length, length-width ratio, chalky rice percentage, chalkiness degree, transparency), and cooking quality (alkali spreading value, gel consistency, amylose). Principal component analysis was used to distinguish the regional quality of southern rice. The results showed that amylose and chalkiness were the main contributory quality indexes of rice in South China, the upper reaches of the Yangtze River, and the middle and lower reaches of the Yangtze River. In the past decade, the total high-quality rate of rice in the South has improved. The random forest was used to determine the important influence index of rice quality. The results showed that chalkiness degree, alkali spreading value, and gel consistency were important indexes affecting the quality of southern rice, and random forest could be used as an effective approach for continuous monitoring and analysis of rice quality.
Antimicrobial Effects of Gum Arabic‐Silver Nanoparticles against Oral Pathogens
Authors: Ahmed Omnia , Sibuyi Nicole R. S. , Fadaka Adewale O. , Madiehe Abram M. , Maboza Ernest , Olivier Annette , Meyer Mervin , Geerts Greta
Published: December 2022

Dental caries is considered one of the most prevalent oral diseases worldwide, with a high rate of morbidity among populations. It is a chronic infectious disease with a multifactorial etiology that leads to the destruction of the dental tissues. Due to their antimicrobial, anti‐inflammatory, antifungal, and antioxidant properties; silver nanoparticles (AgNPs) are incorporated in dental products to help prevent infectious oral diseases. In this study, the antimicrobial effects of AgNPs synthesized using Gum Arabic extracts (GAE) were examined. The GA‐AgNPs were synthesized and characterized using ultraviolet‐visible (UV‐Vis) spectrophotometer, dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. The antimicrobial activity of the GA‐AgNPs was evaluated on Streptococcus sanguinis (S. sanguinis), Streptococcus mutans (S. mutans), Lactobacillus acidophilus (L. acidophilus), and Candida albicans (C. albicans) using agar disc diffusion and microdilution assays. The antibiofilm of GA‐AgNPs was evaluated on the surface of human tooth enamel that had been exposed to S. mutans with and without the GA‐AgNPs using scanning electron microscopy (SEM). GA‐AgNPs were spherical in shape with a particle size distribution between 4 and 26 nm. The GA‐AgNPs exhibited antimicrobial activity against all the tested oral microbes, with GA‐AgNPs_0.4g having higher antimicrobial activity. The GA‐AgNPs_0.4g inhibited S. mutans adhesion and biofilm formation on the surface of the tooth enamel. Therefore, this study supports the prospective implementation of the plant extract‐mediated AgNPs in dental healthcare.
Understanding Daily, Emotional, and Physical Burdens and Needs of Parents Caring for Children with Type 1 Diabetes
Authors: Saßmann Heike , Kim-Dorner Su-Jong , Berndt Verena , Biester Torben , Dehn-Hindenberg Andrea , Heidtmann Bettina , Jorch Norbert , Lilienthal Eggert , Nellen-Hellmuth Nicole , Neu Andreas , Schaaf Katja , Ziegler Ralph , Lange Karin
Published: December 2022

Aims. To investigate (1) daily, emotional, and physical caregiving burdens in parents of children with type 1 diabetes, (2) the sociodemographic and clinical predictors of three burdens, and (3) support measures that parents wish to receive. Methods. The study was a multicenter cross-sectional survey conducted in nine German pediatric diabetes centers. A questionnaire assessing three types of burdens and wishes for support was distributed to parents with a child with type 1 diabetes visiting one of the pediatric centers for a routine check-up. Results. Data from 1,107 parents (83% mothers) were analyzed. Parents reported significantly higher emotional burdens compared to daily and physical burdens (

p
<
0.0001

). Mothers felt more burdened than fathers did. Parents of younger children reported higher daily and physical burdens compared to the parents of older children, and similarly, parents of technology users reported higher daily and physical burdens compared to the parents of nontechnology users. However, emotional burdens did not differ in both comparisons. Other demographic factors (i.e., parent’s age, migration status, and single-parent family status) predicted high levels of daily or physical burdens, but only HbA1c level and the parent’s gender (mother) predicted a high emotional burden. Independent of the level of burden, 78% of parents wanted additional diabetes training. Conclusion. Despite parents reporting high emotional burdens in connection with diabetes care, HbA1c and the gender of the reporting parent were the only risk factors. As the child gets older, parents’ daily and physical distress decrease but not the emotional burden. Diabetes training including regularly offered booster sessions as well as low-threshold interventions for mental health issues and practical self-care skills is recommended to provide continuous support for parents.
Impaired SARS-CoV-2 Variant Neutralization and CD8+ T-cell Responses Following 3 Doses of mRNA Vaccines in Myeloma: Correlation with Breakthrough Infections
Authors: Azeem Maryam I. , Nooka Ajay K. , Shanmugasundaram Uma , Cheedarla Narayanaiah , Potdar Sayalee , Manalo Renee Julia , Moreno Alberto , Switchenko Jeffrey M. , Cheedarla Suneethamma , Doxie Deon Bryant , Radzievski Roman , Ellis Madison Leigh , Manning Kelly E. , Wali Bushra , Valanparambil Rajesh M. , Maples Kathryn T. , Baymon Essence , Kaufman Jonathan L. , Hofmeister Craig C. , Joseph Nisha S. , Lonial Sagar , Roback John D. , Sette Alessandro , Ahmed Rafi , Suthar Mehul S. , Neish Andrew S. , Dhodapkar Madhav V. , Dhodapkar Kavita M.
Published: December 2022

Patients with multiple myeloma (MM) mount suboptimal neutralizing antibodies (nAb) following 2 doses of SARS-CoV-2 mRNA vaccines. Currently, circulating SARS-CoV-2 variants of concern (VOC) carry the risk of breakthrough infections. We evaluated immune recognition of current VOC including BA.1, BA.2, and BA.5 in 331 racially representative patients with MM following 2 or 3 doses of mRNA vaccines. The third dose increased nAbs against WA1 in 82%, but against BA variants in only 33% to 44% of patients. Vaccine-induced nAbs correlated with receptor-binding domain (RBD)–specific class-switched memory B cells. Vaccine-induced spike-specific T cells were detected in patients without seroconversion and cross-recognized variant-specific peptides but were predominantly CD4+ T cells. Detailed clinical/immunophenotypic analysis identified features correlating with nAb/B/T-cell responses. Patients who developed breakthrough infections following 3 vaccine doses had lower live-virus nAbs, including against VOC. Patients with MM remain susceptible to SARS-CoV-2 variants following 3 vaccine doses and should be prioritized for emerging approaches to elicit variant-nAb and CD8+ T cells.

Significance:

Three doses of SARS-CoV-2 mRNA vaccines fail to yield detectable VOC nAbs in nearly 60% and spike-specific CD8+ T cells in >80% of myeloma patients. Patients who develop breakthrough infections following vaccination have low levels of live-virus nAb.

This article is highlighted in the In This Issue feature, p. 101
Antibody Binding and Neutralization of Live SARS-CoV-2 Variants Including BA.4/5 Following Booster Vaccination of Patients with B-cell Malignancies
Authors: Chang Andres , Akhtar Akil , Lai Lilin , Orellana-Noia Victor M. , Linderman Susanne L. , McCook-Veal Ashley A. , Switchenko Jeffrey M. , Saini Manpreet , Valanparambil Rajesh M. , Blum Kristie A. , Allen Pamela B. , Lechowicz Mary Jo , Romancik Jason T. , Ayers Amy , Leal Alyssa , O'Leary Colin B. , Churnetski Michael C. , Baird Katelin , Kives Melissa , Wrammert Jens , Nooka Ajay K. , Koff Jean L. , Dhodapkar Madhav V. , Suthar Mehul S. , Cohen Jonathon B. , Ahmed Rafi
Published: December 2022

Patients with non–Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL) elicit inadequate antibody responses after initial SARS-CoV-2 vaccination and remain at high risk of severe COVID-19 disease. We investigated IgG, IgA, and IgM responses after booster vaccination against recent SARS-CoV-2 variants including Omicron BA.5 in 67 patients. Patients had lower fold increase and total anti-spike binding titers after booster than healthy individuals. Antibody responses negatively correlated with recent anti-CD20 therapy and low B-cell numbers. Antibodies generated after booster demonstrated similar binding properties against SARS-CoV-2 variants compared with those generated by healthy controls with lower binding against Omicron variants. Importantly, 43% of patients showed anti-Omicron BA.1 neutralizing antibodies after booster and all these patients also had anti-Omicron BA.5 neutralizing antibodies. Patients with NHL/CLL demonstrated inferior antibody responses after booster vaccination, particularly against Omicron variants. Prioritization of prophylactic and treatment agents and vaccination of patients and close contacts with updated vaccine formulations are essential.

Significance:

Limited data exist on antibody responses against current SARS-CoV-2 variants after booster vaccination in patients with NHL/CLL. We showed inferior antibody responses against Omicron variants after booster vaccination in these patients but some generated anti-Omicron titers. This stresses the importance of vaccinating patients with updated formulations.
The Clinical Utility and Cost of Routine Staging Exam under Anesthesia for Oral Cavity Squamous Cell Carcinoma
Authors: Hamdi Osama A. , Dougherty Michael I. , Rasamny Jk J. , Greyson Mark A. , Christophel John J. , Shonka Jr. David C. , Fedder Katherine L. , Jameson Mark J. , Garneau Jonathan C.
Published: December 2022

Introduction: The standard complete evaluation of patients with head and neck squamous cell carcinoma (HNSCC) has included a staging exam under anesthesia (EUA) since the 1970s. The EUA for all sites of HNSCC has historically consisted of panendoscopy for the purpose of diagnostic biopsy, accurate staging of primary disease, and identification of second primary tumors. However, due to the accessibility of the oral cavity, the sole purpose of EUA for tumors of this site is to identify second primary tumors. Since the EUA became the gold standard for evaluation of HNSCC, there have been significant advancements in less invasive technologies such as CT, PET-CT, MRI, and fiberoptic examination. In this study, we sought to determine the value to patient care and cost-effectiveness of EUA in patients with oral cavity squamous cell carcinoma (OCSCC). Methods: A retrospective chart review identified 77 patients who underwent EUA for OCSCC. Results: The most common subsites were the oral tongue and floor of mouth (59.7% and 24.7% respectively). All underwent direct laryngoscopy, 94.8% underwent esophagoscopy, and 20.8% underwent flexible transnasal examination in clinic prior to EUA. For 90.9% of patients, the EUA did not change initial T-staging based on clinical examination and imaging. The remaining 9.1% of patients were upstaged after EUA, however this change did not impact the treatment plan. Second primary tumors were identified in 3.9% of patients, all were found in either the oral cavity or oropharynx, and were also identified with clinical examination or imaging. Analysis of patient charges determined an average cost of $8,022.93 per patient under the current paradigm involving EUA, however with a new algorithm eliminating mandatory EUA average cost decreases to $1,448.44. Conclusion: Formal EUA has historically been the gold standard for all HNSCC tumors. However, when performed for cases of oral cavity carcinoma, it is safe and cost effective to limit its use to select clinical scenarios.
Connexin 43 across the Vasculature: Gap Junctions and Beyond
Authors: Sedovy Meghan W. , Leng Xinyan , Leaf Melissa R. , Iqbal Farwah , Payne Laura Beth , Chappell John C. , Johnstone Scott R.
Published: December 2022

Connexin 43 (Cx43) is essential to the function of the vasculature. Cx43 proteins form gap junctions that allow for the exchange of ions and molecules between vascular cells to facilitate cell-to-cell signaling and coordinate vasomotor activity. Cx43 also has intracellular signaling functions that influence vascular cell proliferation and migration. Cx43 is expressed in all vascular cell types, although its expression and function vary by vessel size and location. This includes expression in vascular smooth muscle cells (vSMC), endothelial cells (EC), and pericytes. Cx43 is thought to coordinate homocellular signaling within EC and vSMC. Cx43 gap junctions also function as conduits between different cell types (heterocellular signaling), between EC and vSMC at the myoendothelial junction, and between pericyte and EC in capillaries. Alterations in Cx43 expression, localization, and post-translational modification have been identified in vascular disease states, including atherosclerosis, hypertension, and diabetes. In this review, we discuss the current understanding of Cx43 localization and function in healthy and diseased blood vessels across all vascular beds.
The Effectiveness of Metacognitive Therapy Compared to Behavioral Activation for Severely Depressed Outpatients: A Single-Center Randomized Trial
Authors: Schaich Anja , Outzen Janne , Assmann Nele , Gebauer Carlotta , Jauch-Chara Kamila , Alvarez-Fischer Daniel , Hüppe Michael , Wells Adrian , Schweiger Ulrich , Klein Jan Philipp , Fassbinder Eva
Published: December 2022

Introduction: Major depressive disorder (MDD) is a highly prevalent and disabling disorder. This study examines two psychotherapy methods for MDD, behavioral activation (BA), and metacognitive therapy (MCT), when applied as outpatient treatments to severely affected patients. Methods: The study was conducted in a tertiary outpatient treatment center. Patients with a primary diagnosis of MDD (N = 122) were included in the intention-to-treat sample (55.7% female, mean age 41.9 years). Participants received one individual and one group session weekly for 6 months (M). Assessments took place at baseline, pretreatment, mid-treatment (3 M), post-treatment (6 M), and follow-up (12 M). The primary outcome was depressive symptomatology assessed by the Hamilton Rating Scale for Depression at 12 M follow-up. Secondary outcomes included general symptom severity, psychosocial functioning, and quality of life. Results: Linear mixed models indicated a change in depressive symptoms (F(2, 83.495) = 12.253, p < 0.001) but no between-group effect (F(1, 97.352) = 0.183, p = 0.670). Within-group effect sizes were medium for MCT (post-treatment: d = 0.610; follow-up: d = 0.692) and small to medium for BA (post-treatment: d = 0.636, follow-up: d = 0.326). In secondary outcomes, there were improvements (p ≤ 0.040) with medium to large within-group effect sizes (d ≥ 0.501) but no between-group effects (p ≥ 0.304). Response and remission rates did not differ between conditions at follow-up (response MCT: 12.9%, BA: 13.3%, remission MCT: 9.7%, BA: 10.0%). The deterioration rate was lower in MCT than in BA (χ21 = 5.466, p = 0.019, NTT = 7.4). Discussion: Both MCT and BA showed symptom reductions. Remission and response rates were lower than in previous studies, highlighting the need for further improvements in adapting/implementing treatments for severely affected patients with MDD.
Critical Appraisal of Limitations in the Current Definition/Classification of Uremic Toxins
Authors: Husain-Syed Faeq , Vanholder Raymond , Rosner Mitchell H. , Kawanishi Hideki , Sirich Tammy Lisa , Ronco Claudio
Published: December 2022

Progress in the identification and characterization of uremic retention solutes has refined our understanding of the pathophysiology of the uremic syndrome. Furthermore, the evolution of dialysis and other techniques designed to remove uremic retention solutes offers opportunities to provide a more personalized and targeted treatment for patients with chronic kidney disease (CKD) with an aim to improve outcomes. Considering these developments, a consensus report was recently published that readdressed the 2003 definition and classification of uremic toxins and formulated recommendations for future research to enhance the understanding of uremic retention solutes. In the present work, the authors of a work group that contributed to the consensus report provide a more detailed rationale for the recommendations related to their theme “Critical appraisal of limitations in the current definition/classification of uremic toxins.” In summary, the authors propose that the current definition of uremic toxins should remain organized on hemodialysis strategies, membranes, and removal patterns since hemodialysis is the most frequently applied therapeutic strategy to reduce their concentration in advanced CKD. Nevertheless, the work group also acknowledges that any classification based on cutoff values and/or molecular spatial configurations is arbitrary and will likely need to be changed with therapeutic advancements. Furthermore, the current physicochemical classification might be extended to reflect the degree of toxicity of a specific toxin that is likely to support more personalized and targeted dialysis prescriptions and improve the outcomes for patients with CKD.
Impact of the Introduction of a Public Taxi Ride in Rural South Korea on Levels of Healthcare Utilization among Elderly Patients with Diabetes
Authors: Choi Mingee , Kim Woorim , Kim Dae Hyun , Shin Jaeyong
Published: December 2022

Introduction: A nine-cent public taxi ride service was introduced to improve public transportation in the rural county of Seocheon, which has an ageing population. This study investigated the effect of this policy on the levels of healthcare utilization in individuals with diabetes aged 65 years or above. Methods: The Korea National Health Insurance System claims data from January 2006 to May 2013 (pre-intervention) and June 2013 to December 2014 (post-intervention) were used. The treatment group consisted of patients residing in Seocheon, and the control group consisted of patients residing in neighbouring areas with a similar demographic composition. The difference-in-difference approach was used to estimate differences in levels of healthcare utilization between the treatment and control groups before and after the intervention period. Results: The introduction of public taxi transportation service was associated with an increase in outpatient visits. Specifically, the number of outpatient visits to public health centres increased, whereas those to tertiary hospitals decreased. The number of inpatient visits to general hospitals also increased. Conclusion: The results of this study confirm a relationship between the introduction of public taxi transportation services and increased healthcare utilization in older patients with diabetes in rural areas. These findings are noteworthy considering the importance of continuous care in managing chronic diseases.
Embasamento político das concepções e práticas referentes às drogas no Brasil
Authors: Souza Jacqueline de , Kantorski Luciane Prado
Published: December 2022

Trata-se de reflexão teórica que tem como eixo a concepção da problemática das drogas nas políticas públicas brasileiras. Tal reflexão foi sistematizada a partir dos documentos: Política Nacional sobre Drogas e Política do Ministério da Saúde para Atenção Integral aos Usuários de Álcool e outras Drogas. O objetivo é mostrar o panorama do modo como tais políticas orientam as ações da sociedade e, sobretudo, dos serviços de saúde no tocante ao uso e usuários de substâncias psicoativas no Brasil, bem como apresentar um quadro sobre a estruturação nacional dos órgãos relacionados às políticas públicas nesse setor, além disso, ressaltar os principais parâmetros que subsidiam a Política do Ministério da Saúde para Atenção Integral aos Usuários de Álcool e outras Drogas, possibilitando a visualização do lócus que ela ocupa na Política Nacional.
Osteoprotegerin and Ischemic Stroke Prognosis: A Prospective Multicenter Study and Mendelian Randomization Analysis
Authors: Zhu Zhengbao , Guo Daoxia , Zhang Kaixin , Yang Pinni , Jia Yiming , Shi Mengyao , Peng Yanbo , Chen Jing , Wang Aili , Xu Tan , Zhang Yonghong , He Jiang
Published: December 2022

Background:

Osteoprotegerin was implicated in vascular injury and inflammatory responses, but its prognostic value in ischemic stroke remained unclear. We aimed to prospectively investigate the association between plasma osteoprotegerin and ischemic stroke prognosis combined with a Mendelian randomization analysis.

Methods:

Our prospective study follows the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) reporting guideline. We measured baseline plasma osteoprotegerin levels for 3490 ischemic stroke patients recruited between August 2009 and May 2013 in 26 hospitals across China. The primary outcome was a composite outcome of death and major disability at 3 months after ischemic stroke.

Results:

After adjustment for age, sex, admission National Institutes of Health Stroke Scale score, and other important covariates, elevated osteoprotegerin levels were associated with increased risks of primary outcome (odds ratio, 1.40 [95% CI, 1.05–1.88]), death (hazard ratio, 2.05 [95% CI, 1.04–4.08]), and composite outcome of death and vascular events (hazard ratio, 2.00 [95% CI, 1.15–3.48]) when 2 extreme quartiles were compared. Each 1-SD higher log-osteoprotegerin was associated with a 18% (95% CI, 6%–32%) increased risk of primary outcome, 69% (95% CI, 31%–118%) increased risk of death, and 53% (95% CI, 24%–89%) increased risk of composite outcome of death and vascular events, respectively. Multiple-adjusted spline regression model showed a linear association of osteoprotegerin with primary outcome (
P
for linearity <0.001). Adding osteoprotegerin to conventional risk factors did not significantly improve discriminatory power (C statistics, 0.817 versus 0.818;
P
=0.232) but did slightly improve the risk reclassification of primary outcome (net reclassification improvement: 13.68%,
P
<0.001; integrated discrimination improvement: 0.23%,
P
=0.039). In Mendelian randomization analysis, genetically determined high plasma osteoprotegerin was associated with increased risk of primary outcome (odds ratio, 5.74 [95% CI, 1.12–29.44];
P
=0.036).

Conclusions:

Elevated plasma osteoprotegerin was associated with poor prognosis of ischemic stroke, and genetically determined high plasma osteoprotegerin was associated with an increased risk of primary outcome in Mendelian randomization analysis.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01840072.
Morphological and anatomical analyses clarify the species definition of Ceratozamia latifolia Miq. (Zamiaceae) and lead to the description of a new species: Ceratozamia reesii
Authors: VOVIDES ANDREW P. , PÉREZ-FARRERA MIGUEL ANGEL , SALINAS-RODRÍGUEZ MARÍA MAGDALENA , GALICIA SONIA , DÍAZ-JIMÉNEZ PEDRO , CALONJE MICHAEL , GUTIÉRREZ-ORTEGA JOSÉ SAID
Published: December 2022

The cycad Ceratozamia latifolia was first described by Miquel in 1847 based on plant of unknown provenance cultivated in Hortus Botanicus in Amsterdam which was obtained from Belgium, and for which no type specimen was collected or preserved. The description was based on a juvenile plant, lacked a detailed explanation of the species’ characteristics, and had no accompanying illustrations. Since then, the concept of C. latifolia long time remained as a nomen dubium, often referring to a species probably from Veracruz, Mexico. However, the neotypification of C. latifolia in 1986 linked the poor description of C. latifolia to a known population from San Luis Potosí (SLP), Mexico. This neotypification brought complications to the taxonomy of the genus: 1) Because the neotype population belonged to the then recently described species C. microstrobila, C. microstrobila fell into synonymy with C. latifolia due to nomenclatural priority. 2) Because the neotypification of the name was part of a paper focused on nomenclature, no description, circumscription, or formal synonymizations were made, leaving the correct application of the name C. latifolia unclear. This ambiguity led taxonomists and horticulturists to identify plants from different populations of SLP as C. latifolia, even though the morphological differences among populations were clear. In this study, we focus in a group of populations from the Municipality of Xilitla, SLP, that were considered to be C. latifolia since 1980s. However, when comparing the morphology between wild C. latifolia plants and the plants from Xilitla, they differ in multiple vegetative and reproductive traits. Here, we present morphological and anatomical data to demonstrate that these populations from Xilitla do not correspond to the current concept of C. latifolia or to the southern neighbors C. chamberlainii or C. fuscoviridis, but rather they belong to a new species that we describe as C. reesii sp. nov.