bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of target-controlled infusion of lidocaine undergoing vocal cord polypectomy
Authors: Zhou LongYuan , Wu RuiLan , Cai Chang , Qi Yong , Bi XingHua , Hang Qi
Published: February 2022

Background:

The present study aimed to assess the efficacy and safety of general anesthesia-assisted target-controlled plasma infusion of lidocaine in patients with vocal cord polypectomy using a supporting laryngoscope.

Methods:

In total, 80 patients undergoing vocal cord polypectomy using a supporting laryngoscope were randomly divided into an intervention group and a control group; each group contained 40 subjects: both groups received general anesthesia; subjects in the intervention also received an additional 3 mg/L of lidocaine by target-controlled plasma infusion during induction and maintenance of anesthesia; heart rate (HR) mean arterial pressure (MAP), propofol and urapidil consumption (Uradil, which is a blood pressure drug that blocks alpha-1, is called Urapidi Hydrochloride Injection. It is produced by Germany, the enterprise name is Nycomed Deutschland GmbH, the import drug registration number is H20090715, and it is widely used in China), recovery time, and cough score (measured by Minogue et al's 5-grade scoring method) during extubation, and throat pain score (measured by visual analogue scale,[VAS]) after extubation and adverse events were recorded.

Results:

Significant differences were observed in HR (P < .05) and MAP (P < .05) immediately after intubation (T2), immediately after the operation starting to support laryngoscope exposure (T3), immediately after operation field adrenergic tampon hemostasis (T4), and 5 minutes after hemostasis (T5) between the 2 groups, and significant differences were also observed in HR (P < .05) before intubation (T1). Moreover, significant differences were observed in propofol consumption (P < .05), urapidil consumption (P < .05), cough score during extubation (P < .05), and throat pain score after extubation (P < .05). However, no significant difference was observed in the recovery time (P > .05). Furthermore, no adverse events were detected in either group.

Conclusion:

The results of this study showed that target-controlled plasma infusion of lidocaine can reduce propofol consumption in patients undergoing vocal cord polypectomy by supporting laryngoscopy, and the hemodynamics are more stable and reduce the coughing reaction in the wake period and throat pain after extubation without adverse events.
Global trends of researches on bone metastasis
Authors: Huang Kai
Published: February 2022

Background:

Bone metastasis (BM) has become an important health problem. In recent years, studies on BM are growing rapidly, but there were no bibliometric studies regarding BM. This study aimed to illustrate the overall knowledge structure and development trends of BM.

Methods:

Research datasets were acquired from the Web of Science database. The time span was defined as “1980–2020”. VOS viewer and Citespace software was provided to analyze the data and generate visualization knowledge maps. Annual trends of publications, distribution, H-index status, co-authorship status, and research hotspots were analyzed.

Results:

Six hundred eighty-two publications met the requirement. USA published most papers (264, 38.7%), and both total citations (13,997) and H-index (57) of USA ranked first. The most productive institution on BM is Amgen Inc. (43). Supportive Care in Cancer (24) published the most papers on BM. “Safety”, “skeletal related event”, “open label”, “management”, “health”, and “prognosis” are the research hotspots in the recent years.

Conclusion:

In this study, we conduct a systematic and comprehensive analysis on the research in BM field. The publication number was rising in recent years stably. USA contributed mostly not only in quality, but also in quantity. Amgen Inc. published the largest number of articles, Supportive Care in Cancer was the most productive journal related to BM. “Safety”, “skeletal related event”, “open label”, “management”, “health”, and “prognosis” are the research hotspots in recent years. We believe this study can not only show the global research overview in past 40 years but also point the research trend of BM in the future.
Effects of vitamin D supplementation on ovarian reserve markers in infertile women with diminished ovarian reserve
Authors: Bacanakgil Besim Haluk , İlhan Gülşah , Ohanoğlu Karolin
Published: February 2022

The purpose of this study was to evaluate the effects of vitamin D supplementation on ovarian reserve markers, including serum anti-Mullerian hormone (AMH) level, follicle-stimulating hormone (FSH) level, and antral follicle count (AFC), in infertile women with diminished ovarian reserve and vitamin D deficiency.

A prospective, nonrandomized, cross-sectional study was conducted. Women aged 18 to 41 years who were unable to become pregnant after 12 months of sexual intercourse and had normal tubal patency, partners with normal semen analysis, diminished ovarian reserve, and 25-hydroxyvitamin D [25(OH)D] deficiency were included. Eligible patients’ AFC and serum levels of AMH, FSH, 25(OH)D, 1,25-dihydroxyvitamin D [1,25(OH)D], calcium, phosphate, alkaline phosphatase, and parathormone were assessed before and after administration of 300,000 IU of vitamin D ampules. Changes in the parameter values after vitamin D supplementation were compared with the initial levels.

The study was conducted in 62 of the 142 participants. The AFC and AMH, 25(OH)D, 1,25(OH)D, phosphate (P < .01), and calcium levels (P < .05) were statistically significantly increased after vitamin D supplementation. Statistically significant decreases in FSH (P < .01) and alkaline phosphatase levels (P < .05) were observed after vitamin D supplementation. No statistically significant correlations were found between 25(OH)D level and AFC, 1,25(OH)D level, AMH level, and FSH level before and after supplementation (P > .05).

As improvements in the ovarian reserve markers were obtained with vitamin D supplementation, vitamin D might be considered as a fertility treatment for patients with diminished ovarian reserve and vitamin D deficiency.
Expression and prognostic impact of CD49b in human lung cancer
Authors: Tirilomi Anna , Elakad Omar , Yao Sha , Li Yuchan , Hinterthaner Marc , Danner Bernhard C. , Ströbel Philipp , Tirilomis Theodor , Bohnenberger Hanibal , von Hammerstein-Equord Alexander
Published: February 2022

Lung cancer remains the worldwide leading cause of cancer-related death. Currently, prognostic biomarkers for the detection and stratification of lung cancer are being investigated for clinical use. The surface protein cluster of differentiation 49b (CD49b) plays an important role in promoting cell proliferation and invasion in different tumor entities and blocking CD49b improved the tumor immune response. Overexpression of CD49b has been associated with unfavorable survival rates in several malignant tumor entities, such as prostate cancer, gastric cancer and colon cancer. Therefore, we aimed to analyze the protein expression of CD49b in patients with different types of lung cancer and additionally to identify the influence of CD49b on clinicopathological characteristics and overall survival.

Expression levels of CD49b were retrospective analyzed by immunohistochemistry in 92 cases of pulmonary adenocarcinoma (AC), 85 cases of squamous cell lung carcinoma (SQCLC) and 32 cases of small cell lung cancer (SCLC) and correlated with clinicopathological characteristics and patients’ overall survival.

A strong expression of CD49b was most seen in SQCLC (78%), followed by AC (48%) and SCLC (9%). All patients combined, strong expression of CD49b correlated significantly with poorer overall survival. However, an increased expression of CD49b correlated significantly with a poorer survival rate only in SQCLC. In AC and SCLC, no significant correlation could be demonstrated in this regard.

In our study, CD49b expression was associated with poor overall survival in patients with SQCLC. Accordingly, CD49b could serve as a new prognostic biomarker and, moreover, be a potential new drug target in SQCLC.
Barriers and Facilitators to Success in Undergraduate Nursing Education Among Minority Students
Authors: Osakwe Zainab Toteh , Obioha Chinedu U. , Minuti Aurelia , Atairu Minne , Osborne Jennel C.
Published: February 2022

Background:

Underrepresented minority (URM) students in nursing education are essential to address health disparities.

Purpose:

To determine barriers and facilitators to success among URM students in nursing education.

Methods:

CINAHL, PubMed, Embase, and PsycINFO were searched for English language research studies published between 1980 and 2020, which focused on barriers and facilitators to success in nursing education in the United States among URM students. Using PRISMA guidelines, 2 reviewers independently reviewed and appraised the quality of relevant articles.

Results:

Among the 4435 articles surveyed, 14 met inclusion criteria. Most studies were focused on Black and Hispanic/Latinx students, and 71% were qualitative. Barriers included social isolation, caregiving demands, lack of mentorship, and inadequate financial resources. Facilitators included mentorship, positive class and curriculum, family support, financial support, and diverse/inclusive learning environments.

Conclusions:

URM students face complex barriers to success in nursing education. Addressing these barriers requires a multilevel approach.
Assessment of Adult Women With Ovarian Masses and Treatment of Epithelial Ovarian Cancer: ASCO Resource-Stratified Guideline
Authors: Vanderpuye Verna D. , Clemenceau Jean Rene V. , Temin Sarah , Aziz Zeba , Burke William M. , Cevallos Nixon Leonardo , Chuang Linus T. , Colgan Terence J. , del Carmen Marcela G. , Fujiwara Keiichi , Kohn Elise C. , Nogales Jose Enrique Gonzáles , Konney Thomas Okpoti , Mukhopadhyay Asima , Paudel Bishnu D. , Tóth Icó , Wilailak Sarikapan , Ghebre Rahel G.
Published: February 2022

(Abstracted from JCO Glob Oncol 2021;7:1032–1066)

The lack of reliable screening modalities for ovarian cancer results in most women being diagnosed on the basis of symptomatic presentation with the majority at advanced stages. Nonspecific symptoms may be overlooked or misdiagnosed regardless of how resource-rich the health care system.
Retrograde Bladder Filling After Outpatient Gynecologic Surgery: A Systematic Review and Meta-Analysis
Authors: Thiel Peter S. , Mathur Siddhi , Zakhari Andrew , Matelski John , Walsh Chris , Murji Ally
Published: February 2022

(Abstracted from Obstet Gynecol 2021;138:647–654)

The potential for impaired bladder function after outpatient or inpatient gynecologic surgery has led many centers to require a successful voiding trial before discharge. Partially retrofilling the bladder has been investigated in various gynecologic surgery populations to reduce time spent waiting for passive filling.
Why Stuttering Occurs
Authors: Usler Evan R.
Published: February 2022

The purpose of this article is to provide a theoretical account of the experience of stuttering that incorporates previous explanations and recent experimental findings. According to this account, stuttering-like disfluencies emerge during early childhood from excessive detection of cognitive conflict due to subtle limitations in speech and language processes. For a subset of children who begin to stutter, the development of approach-avoidance motivational conflict likely contributes to a chronic reliance on cognitive control processes during speech. Consequently, maladaptive activation of right hemisphere inhibitory cortices to the basal ganglia via a hyperdirect pathway results in involuntary, episodic, and transient freezing of the motor system during speech initiation. This freeze response, consistent with defensive behavior in threatening situations, may lead to stuttering persistence, tension and struggle, maladaptive speech physiology, and feelings of anxiety and loss of control.
Immunosuppression and SARS-CoV-2 Infection in Kidney Transplant Recipients
Authors: Devresse Arnaud , De Greef Julien , Yombi Jean Cyr , Belkhir Leila , Goffin Eric , Kanaan Nada
Published: February 2022

Kidney transplant recipients (KTRs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have an increased risk of mortality compared with the general population and hemodialysis patients. As these patients are immunosuppressed, it might seem obvious to attribute this excess mortality to the impaired immunity induced by immunosuppression. In line with this reasoning is the low immune response, both cellular and humoral, that KTRs mount in response to the anti–SARS-CoV-2 vaccine; however, acute respiratory distress syndrome associated with coronavirus disease 2019 is triggered by a state of inflammation and cytokine release syndrome that lead to pulmonary damage and increased mortality. In that context, immunosuppressive treatment dampening the immune response could, in theory, be potentially beneficial.

This review aims at analyzing the current knowledge on the impact of immunosuppressive treatment on mortality in SARS-CoV-2–infected KTRs, the optimal management of immunosuppression in the coronavirus disease 2019 era, and the vaccine response and management in immunosuppressed KTRs.
The Practice of Retransplantation for Recurrent Alcohol-associated Liver Disease in the United States Is Uncommon With Acceptable Outcomes
Authors: Cotter Thomas G. , Odenwald Matthew A. , Lieber Sarah R. , Rich Nicole E. , Im Gene , Charlton Michael , Singal Amit G. , Mitchell Mack C.
Published: February 2022

Background.

Alcohol-associated liver disease (ALD) is the leading indication for liver transplantation (LT) in the United States. Alcohol use disorder relapse can lead to graft failure and the need for liver retransplantation (re-LT). Despite the rising incidence of LT for ALD, the practice of re-LT for recurrent ALD is not well understood. We aimed to define the practice of re-LT for recurrent ALD during the last 20 y.

Methods.

Using the US national transplant registry, adults who underwent re-LT for recurrent ALD were compared with LT recipients who died from recurrent ALD and propensity score–matched re-LT recipients with non-ALD indications. All groups had at least 1-y survival of their primary graft. Kaplan-Meier analysis was used to calculate 1- and 5-y survivals.

Results.

Between 2000 and 2020, 74 re-LTs were performed for recurrent ALD (1.0% of all re-LTs). There was an increase in recurrent ALD re-LT practice from 2017 to 2020 versus 2014 to 2016 (20 versus 2). At the time of re-LT, patients with recurrent ALD had a significant decrease in body mass index (median 25.1 versus 28.8 kg/m2; P < 0.001) versus the index LT. Patient and graft survivals were similar between patients who underwent re-LT for ALD and non-ALD (56.4% versus 56.9% 5-y graft survival, P = 0.96; 62.8% versus 59.0% 5-y patient survival, P = 0.58).

Conclusions.

The practice of re-LT for recurrent ALD is uncommon in the United States. Graft and patient survivals seem to be acceptable and support the occasional practice of re-LT for recurrent ALD should the patient be deemed an appropriate candidate.
Outbreak of SARS-CoV-2 at a hospice: terminated after the implementation of enhanced aerosol infection control measures
Authors: Feathers Luke , Hinde Tracey , Bale Tammy , Hyde Jo , Bird Paul W. , Holmes Christopher W. , Tang Julian W.
Published: February 2022

Outbreaks of COVID-19 in hospices for palliative care patients pose a unique and difficult situation. Staff, relatives and patients may be possible sources and recipients of infection. We present an outbreak of COVID-19 in a hospice setting, during the UK's first pandemic wave. During the outbreak period, 26 patients and 30 staff tested SARS-CoV-2 positive by laboratory-based RT-PCR testing. Most infected staff exhibited some mild, non-specific symptoms so affected staff members may not have voluntarily self-isolated or had themselves tested on this basis. Similarly, for infected patients, most became symptomatic and were then isolated. Additional, enhanced aerosol infection control measures were implemented, including opening of all windows where available; universal masking for all staff, including in non-clinical areas and taking breaks separately; screening for asymptomatic infection among staff and patients, with appropriate isolation (at home for staff) if infected; performing a ventilation survey of the hospice facility. After these measures were instigated, the numbers of COVID-19 cases decreased to zero over the following three weeks. This outbreak study demonstrated that an accurate understanding of the routes of infection for a new pathogen, as well as the nature of symptomatic versus asymptomatic infection and transmission, is crucial for controlling its spread.
Modelling airborne transmission of SARS-CoV-2 using CARA: risk assessment for enclosed spaces
Authors: Henriques Andre , Mounet Nicolas , Aleixo Luis , Elson Philip , Devine James , Azzopardi Gabriella , Andreini Marco , Rognlien Markus , Tarocco Nicola , Tang Julian
Published: February 2022

The COVID-19 pandemic has highlighted the need for a proper risk assessment of respiratory pathogens in indoor settings. This paper documents the COVID Airborne Risk Assessment methodology, to assess the potential exposure of airborne SARS-CoV-2 viruses, with an emphasis on virological and immunological factors in the quantification of the risk. The model results from a multidisciplinary approach linking physical, mechanical and biological domains, enabling decision makers or facility managers to assess their indoor setting. The model was benchmarked against clinical data, as well as two real-life outbreaks, showing good agreement. A probability of infection is computed in several everyday-life settings and with various mitigation measures. The importance of
super-emitters
in airborne transmission is confirmed: 20% of infected hosts can emit approximately two orders of magnitude more viral-containing particles. The use of masks provides a fivefold reduction in viral emissions. Natural ventilation strategies are very effective to decrease the concentration of virions, although periodic venting strategies are not ideal in certain settings. Although vaccination is an effective measure against hospitalization, their effectiveness against transmission is not optimal, hence non-pharmaceutical interventions (ventilation, masks) should be actively supported. We also propose a critical threshold to define an acceptable risk level.
Comparing aerosol number and mass exhalation rates from children and adults during breathing, speaking and singing
Authors: Archer Justice , McCarthy Lauren P. , Symons Henry E. , Watson Natalie A. , Orton Christopher M. , Browne William J. , Harrison Joshua , Moseley Benjamin , Philip Keir E. J. , Calder James D. , Shah Pallav L. , Bzdek Bryan R. , Costello Declan , Reid Jonathan P.
Published: February 2022

Aerosol particles of respirable size are exhaled when individuals breathe, speak and sing and can transmit respiratory pathogens between infected and susceptible individuals. The COVID-19 pandemic has brought into focus the need to improve the quantification of the particle number and mass exhalation rates as one route to provide estimates of viral shedding and the potential risk of transmission of viruses. Most previous studies have reported the number and mass concentrations of aerosol particles in an exhaled plume. We provide a robust assessment of the absolute particle number and mass exhalation rates from measurements of minute ventilation using a non-invasive Vyntus Hans Rudolf mask kit with straps housing a rotating vane spirometer along with measurements of the exhaled particle number concentrations and size distributions. Specifically, we report comparisons of the number and mass exhalation rates for children (12–14 years old) and adults (19–72 years old) when breathing, speaking and singing, which indicate that child and adult cohorts generate similar amounts of aerosol when performing the same activity. Mass exhalation rates are typically 0.002–0.02 ng s
−1
from breathing, 0.07–0.2 ng s
−1
from speaking (at 70–80 dBA) and 0.1–0.7 ng s
−1
from singing (at 70–80 dBA). The aerosol exhalation rate increases with increasing sound volume for both children and adults when both speaking and singing.
An exploration of the political, social, economic and cultural factors affecting how different global regions initially reacted to the COVID-19 pandemic
Authors: Tang Julian W. , Caniza Miguela A. , Dinn Mike , Dwyer Dominic E. , Heraud Jean-Michel , Jennings Lance C. , Kok Jen , Kwok Kin On , Li Yuguo , Loh Tze Ping , Marr Linsey C. , Nara Eva Megumi , Perera Nelun , Saito Reiko , Santillan-Salas Carlos , Sullivan Sheena , Warner Matt , Watanabe Aripuanã , Zaidi Sabeen Khurshid
Published: February 2022

Responses to the early (February–July 2020) COVID-19 pandemic varied widely, globally. Reasons for this are multiple but likely relate to the healthcare and financial resources then available, and the degree of trust in, and economic support provided by, national governments. Cultural factors also affected how different populations reacted to the various pandemic restrictions, like masking, social distancing and self-isolation or self-quarantine. The degree of compliance with these measures depended on how much individuals valued their needs and liberties over those of their society. Thus, several themes may be relevant when comparing pandemic responses across different regions. East and Southeast Asian populations tended to be more collectivist and self-sacrificing, responding quickly to early signs of the pandemic and readily complied with most restrictions to control its spread. Australasian, Eastern European, Scandinavian, some Middle Eastern, African and South American countries also responded promptly by imposing restrictions of varying severity, due to concerns for their wider society, including for some, the fragility of their healthcare systems. Western European and North American countries, with well-resourced healthcare systems, initially reacted more slowly, partly in an effort to maintain their economies but also to delay imposing pandemic restrictions that limited the personal freedoms of their citizens.
The role of SARS-CoV-2 aerosol transmission during the COVID-19 pandemic
Authors: Tang Julian W. , Marr Linsey C. , Li Yuguo , Eames Ian
Published: February 2022

The COVID-19 pandemic, caused by the virus SARS-CoV-2, has touched most parts of the world and devastated the lives of many. The high transmissibility coupled with the initial poor outcome for the elderly led to crushingly high fatalities. The scientific response to the pandemic has been formidable, aided by advancements in virology, computing, data analysis, instrumentation, diagnostics, engineering and infection control. This has led to improvements in understanding and has helped to challenge some established orthodoxies. Sufficient time has elapsed since the start of the COVID-19 pandemic that a clearer view has emerged about transmission and infection risks, public health responses and related societal and economic impacts. This timely volume has provided an opportunity for the science community to report on these new developments.
Chronic Intermittent Hypobaric Hypoxia Prevents Contrast-Induced Acute Kidney Injury By Modulating The HIF-1α Signaling Pathway
Authors: Yin Kai-min , Ni Yan-hui , Cao Guang-yun , Zhang Jia-yuan , Yi Bao-jun , Pang Zi-hao , Ma Hui-jie , Zhang Li
Published: February 2022

The aim of this study was to explore the role of CIHH in preventing contrast-induced acute kidney injury (CI-AKI) in rats and its mechanism. Rats mean arterial pressure, heart rate, serum creatinine and blood urea nitrogen levels were measured. The kidney tissue pathological changes, superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, hypoxia inducible factor-1α, Bcl-2/adenovirus E1B-19kDa-interacting protein3 (BNIP3) , cysteiny aspartate specific protease3(caspase3) and poly(ADP-ribose) polymerase (PARP) expression levels were testing. The results showed that CIHH prevented CI-AKI group mean arterial pressure, heart rate, serum creatinine and blood urea nitrogen levels were reduced, kidney tissue SOD activity was increased, MDA levels was reduced, HIF-1α,BNIP3,caspase3 and PARP levels were increased than the CI-AKI group. This study indicates that CIHH pretreatment may have a protective effect on contrast-induced early kidney injury by activating the HIF-1α/BNIP3 signaling pathway to regulate mitochondrial autophagy and enhance cellular anti-apoptotic and renal antioxidant capacity, for the first time.
The COVID-19 Community Research Partnership: Objectives, Study Design, Baseline Recruitment, and Retention
Authors:   The COVID-19 Community Research Partnership, Sanders John
Published: February 2022

The COVID-19 Community Research Partnership (CCRP) is a multisite surveillance platform designed to characterize the epidemiology of the SARS-CoV-2 pandemic. This manuscript describes the CCRP study design and methodology. The CCRP includes two prospective cohorts, one with six health systems in the mid-Atlantic and southern United States, and the other with six health systems in North Carolina. With enrollment beginning April 2020, sites invited persons within their healthcare systems as well as community members to participate in daily surveillance for symptoms of COVID-like illnesses, testing and risk behaviors. Participants with electronic health records were also asked to volunteer data access. Subsets of participants, representative of the general population and including oversampling of populations of interest, were selected for repeated at home serology testing. By October 2021, 65,739 participants (62,261 adult and 3,478 pediatric) were enrolled with 89% providing syndromic data, 74% providing EHR data, and 70% participating in one of two serology sub-studies. An average of 62% of participants completed a daily survey at least once a week, and 55% of serology kits were returned. The CCRP provides rich regional epidemiologic data and opportunities to more fully characterize the risks and sequelae of SARS-CoV-2 infection.
Diurnal modulation of subthalamic beta oscillatory power in Parkinson’s disease patients during deep brain stimulation
Authors: van Rheede Joram J. , Feldmann Lucia K. , Busch Johannes L. , Fleming John E. , Mathiopoulou Varvara , Denison Timothy , Sharott Andrew , Kühn Andrea A.
Published: February 2022

Background

Beta band activity in the subthalamic local field potential (LFP) is correlated with Parkinson’s disease (PD) symptom severity, and is the therapeutic target and feedback signal for adaptive deep brain stimulation (aDBS). While clinically relevant beta fluctuations in PD patients are well characterised on shorter timescales and in the clinic, it is not known how beta activity evolves around the diurnal cycle, outside a clinical setting.

Objective

To characterise diurnal fluctuations in beta amplitude in PD patients receiving continuous, high frequency DBS.

Methods

We obtained chronic recordings (34±13 days) of subthalamic beta power in PD patients implanted with the Percept DBS device during high-frequency DBS, and analysed its diurnal properties. To investigate the influence of non-frequency-specific effects and artifacts, we compared beta to contralateral theta amplitude and recorded LFPs during various movements.

Results

Beta power had strong 24-hour periodicity, and time of day explained 41±9% of the variance in all long-term beta power recordings (p<0.001 in all patients). For all patients, beta activity was high during the day and reduced at night. Beta activity was not fully explained by theta activity and could show independent diurnal modulation. Movement artifacts affected the recorded LFPs, influenced band power estimates, and could have contributed to diurnal patterns in some patients.

Conclusions

Diurnal fluctuations in beta amplitude will need to be accommodated in aDBS to prevent suboptimal stimulation, particularly at night. Careful screening and/or mitigation of movement artifacts is needed to ensure that the signal is suitable for adaptive stimulation or neurophysiological investigation.
Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progenitors
Authors: Cheong Jin-Gyu , Ravishankar Arjun , Sharma Siddhartha , Parkhurst Christopher N. , Nehar-Belaid Djamel , Ma Sai , Paddock Lucinda , Fatou Benoit , Karakaslar Onur , Thibodeau Asa , Bale Michael J. , Kartha Vinay K. , Yee Jim K , Mays Minh Yen , Leyre Louise , de Paz Alexia Martinez , Daman Andrew W. , Mullett Sergio Alvarez , Robbins Lexi , LaFond Elyse , Weidman Karissa , Racine-Brzostek Sabrina , Yang He S. , Price David , Jones Brad , Schenck Edward J. , Kaner Robert J. , Chadburn Amy , Zhao Zhen , Steen Hanno , Pascual Virginia , Buenrostro Jason , Niec Rachel E. , Lief Lindsay , Ucar Duygu , Josefowicz Steven Z.
Published: February 2022

Severe coronavirus disease 2019 (COVID-19) is characterized by systemic inflammation and can result in protracted symptoms. Robust systemic inflammation may trigger persistent changes in hematopoietic cells and innate immune memory through epigenetic mechanisms. We reveal that rare circulating hematopoietic stem and progenitor cells (HSPC), enriched from human blood, match the diversity of HSPC in bone marrow, enabling investigation of hematopoiesis and HSPC epigenomics. Following COVID-19, HSPC retain epigenomic alterations that are conveyed, through differentiation, to progeny innate immune cells. Epigenomic changes vary with disease severity, persist for months to a year, and are associated with increased myeloid cell differentiation and inflammatory or antiviral programs. Epigenetic reprogramming of HSPC may underly altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.

One Sentence Summary

Transcriptomic and epigenomic analysis of blood reveal sustained changes in hematopoiesis and innate immunity after COVID-19.

Graphical Abstract
Identification of Alkaloids and Related Intermediates of Dendrobium officinale by Solid-Phase Extraction Coupled with High-Performance Liquid Chromatography Tandem Mass Spectrometry
Authors: Song Cheng , Zhang Yunpeng , Manzoor Muhammad Aamir , Li Guohui
Published: February 2022

JA signaling plays a pivotal role in plant stress responses and secondary metabolism. Many studies have demonstrated that jasmonates effectively induce the expressions of alkaloid biosynthesis genes in various plants, which rendered to the accumulation of alkaloid to counteract stresses. Despite the multiple roles of jasmonate (JA) in the regulation of plant growth and different stresses, less studied involved in the regulatory role of JA in D. officinale alkaloids. A strategy for the rapid identification of alkaloid and the intermediates of D. officinale was established based on a solid-phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry method. By using SPE-HPLC-LTQ-Orbitrap method, the potential compounds were tentatively identified by aligning the accurate molecular weight with the METLIN and Dictionary of Natural Products databases. The chemical structures and main characteristic fragments of the potential compounds were further confirmed by retrieving the multistage mass spectra from the MassBank and METLIN databases.The Mass Frontier software was used to speculate the fragmentation pathway of the identified compounds. Seven alkaloids were separated and identified from D. officinale, which were mainly classified into five types (tropane alkaloids, tetrahydroisoquinoline alkaloids, quinolizidine alkaloids, piperidine alkaloids and spermidine alkaloids). Besides the alkaloids, forty-nine chemical substances, including guanidines, nucleotides, dipeptides, sphingolipids and nitrogen-containing glucosides, were concurrently identified. These findings gives the composition of chemicals currently found in D. officinale, which could provide the scientific method for the identification of alkaloids in other Dendrobium plants.
Engineering Defensin α-helix to produce high-affinity SARS-CoV-2 Spike protein binding ligands
Authors: Fernandes Leonardo Antônio , Gomes Anderson Albino , Magalhães Maria de Lourdes Borba , Ray Partha , da Silva Gustavo Felippe
Published: February 2022

The binding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein to the Angiotensin-Converting Enzyme 2 (ACE2) receptor expressed on the host cells is a critical initial step for viral infection. This interaction is blocked through competitive inhibition by soluble ACE2 protein. Therefore, developing high-affinity and cost-effective ACE2 peptidomimetic ligands that disrupt this protein-protein interaction is a promising strategy for viral diagnostics and therapy. We employed human and plant defensins, a class of small and highly stable proteins, and engineered the amino acid residues on its conformationally constrained alpha-helices to mimic the critical residues on the ACE2 helix 1 that interacts with the Spike-protein. The engineered proteins were soluble and purified to homogeneity with high yield from a bacterial expression system. The proteins demonstrated exceptional thermostability, high-affinity binding to the Spike protein with dissociation constants in the low nanomolar range, and were used in a diagnostic assay that detected SARS-CoV-2 neutralizing antibodies. This work addresses the challenge of developing helical peptidomimetics by demonstrating that defensins provide promising scaffolds to engineer alpha-helices in a constrained form for designing high-affinity ligands.

Broad audience statement

The engineered proteins developed in this study are cost-effective and highly stable reagents for SARS-CoV-2 detection. These features may allow large-scale and cost-effective production of diagnostic tests to assist COVID-19 diagnostic and prevention.
Remdesivir and GS-441524 retain antiviral activity against Delta, Omicron, and other emergent SARS-CoV-2 variants
Authors: Pitts Jared , Li Jiani , Perry Jason K. , Du Pont Venice , Riola Nicholas , Rodriguez Lauren , Lu Xianghan , Kurhade Chaitanya , Xie Xuping , Camus Gregory , Manhas Savrina , Martin Ross , Shi Pei-Yong , Cihlar Tomas , Porter Danielle P. , Mo Hongmei , Maiorova Evguenia , Bilello John P.
Published: February 2022

Genetic variation of SARS-CoV-2 has resulted in the emergence and rapid spread of multiple variants throughout the pandemic, of which Omicron is currently the predominant variant circulating worldwide. SARS-CoV-2 variants of concern or interest (VOC/VOI) have evidence of increased viral transmission, disease severity, or decreased effectiveness of vaccines and neutralizing antibodies. Remdesivir (RDV, VEKLURY®) is a nucleoside analog prodrug and the first FDA-approved antiviral treatment of COVID-19. Here we present a comprehensive antiviral activity assessment of RDV and its parent nucleoside, GS-441524, against 10 current and former SARS-CoV-2 VOC/VOI clinical isolates by nucleoprotein ELISA and plaque reduction assay.

Delta and Omicron variants remained susceptible to RDV and GS-441524, with EC50values 0.31 to 0.62-fold of those observed against the ancestral WA1 isolate. All other tested variants exhibited EC50values ranging from 0.15 to 2.3-fold of the observed EC50values against WA1. Analysis of nearly 6 million publicly available variant isolate sequences confirmed that Nsp12, the RNA-dependent RNA polymerase (RdRp) target of RDV and GS-441524, is highly conserved across variants with only 2 prevalent changes (P323L and G671S). Using recombinant viruses, both RDV and GS-441524 retained potency against all viruses containing frequent variant substitutions or their combination. Taken together, these results highlight the conserved nature of SARS-CoV-2 Nsp12 and provide evidence of sustained SARS-CoV-2 antiviral activity of RDV and GS-441524 across the tested variants. The observed pan-variant activity of RDV supports its continued use for the treatment of COVID-19 regardless of the SARS-CoV-2 variant.
High-intensity interval or circuit-based strength training effects on physical and cognitive functioning for community-dwelling older adults: A systematic review protocol
Authors: Morgan Ashley , Noguchi Kenneth S , Tang Ada , Heisz Jennifer , Thabane Lehana , Richardson Julie
Published: February 2022

Background

High-intensity interval or circuit-based strength training utilizes brief intense periods of strengthening exercises interspersed with rest/light activity or performed in a continuous circuit. The physical and cognitive effects of this time-efficient approach in community-dwelling older adults have not been systematically reviewed.

Objectives

To determine the effects of high-intensity interval or circuit-based strength training interventions on physical and cognitive functioning for community-dwelling older adults, and the associated adherence, retention, and adverse event rates.

Methods

Six databases will be searched from inception to November 2021; MEDLINE, EMBASE, CINAHL, AgeLine, SPORTDiscus, and Web of Science. To assess physical and/or cognitive functioning effects, randomized and quasi-randomized controlled trials (RCTs and Q-RCTs) of high-intensity interval or circuit-based strengthening interventions in community-dwelling older adults, utilizing any comparator, will be included. The above criteria will be extended to include non-randomized study designs to assess adherence, retention, and adverse events. All screening, data extraction and risk of bias will be assessed by two independent reviewers. Risk of bias will be assessed utilizing the Cochrane RoB 2 tool for randomized and ROBINS-I for non-randomized studies. Qualitative synthesis will be used to present information on adherence, retention, and adverse event rates. Qualitative and/or quantitative synthesis will be used to present physical and cognitive functioning effects depending on which method is deemed appropriate for the various outcomes.

Conclusion

This systematic review will be the first to summarize the physical and/or cognitive effects, adherence, retention, and adverse events reported in high-intensity interval and circuit-based strengthening interventions for community-dwelling older adults.

Systematic review registration number

CRD42021284010
Acoel single-cell atlas reveals expression dynamics and heterogeneity of a pluripotent stem cell population
Authors: Hulett Ryan E. , Kimura Julian O. , Bolaños D. Marcela , Luo Yi-Jyun , Ricci Lorenzo , Srivastava Mansi
Published: February 2022

Pluripotent adult stem cell populations underlie whole-body regeneration in many distantly related animal lineages. These collectively pluripotent populations of cells share some features across species, such as the expression of piwi and other germline-related genes. Studies of how these cells operate during regeneration are needed in diverse systems to determine how underlying cellular and molecular mechanisms of renewal and differentiation compare. Here, we sought to characterize stem cells and their dynamics in the acoel Hofstenia miamia, a highly regenerative marine worm with a piwi-expressing stem cell population called neoblasts. Transcriptome profiling at single cell resolution revealed cell types shared across postembryonic stages, including stem cells and differentiated cell types such as neural, epidermal, muscle, and digestive cells. Reconstruction of single-cell differentiation trajectories followed by functional studies confirmed that neoblasts are the source of differentiated cells and identified transcription factors needed for the formation of major cell types. Next, analysis of single-cell transcriptomes from regenerating worms showed that both differentiated cells and stem cells dynamically alter gene expression in response to amputation. Further analysis of the stem cells recovered subpopulations of neoblasts, each with specific transcriptional profiles suggesting that the majority of neoblasts are specialized to differentiated lineages, reflecting putatively lineage-primed progenitors. Notably, neoblast subsets in Hofstenia were identifiable consistently across postembryonic stages and also displayed differential expression dynamics in response to wounding. Altogether, these data suggest that whole-body regeneration is accomplished by the coordination of cells with distinct and dynamic transcriptomic profiles through time. Furthermore, the data generated here will enable the study of how this coordination is achieved, enhancing our understanding of pluripotent stem cells and their evolution across metazoans.
False-Positive IRESes from Hoxa9 and other genes resulting from errors in mammalian 5’ UTR annotations
Authors: Akirtava Christina , May Gemma E. , McManus C. Joel
Published: February 2022

Hyperconserved genomic sequences have great promise for understanding core biological processes. It has been recently proposed that scores of hyperconserved transcript leaders (hTLs) encode Internal Ribosome Entry Sites (IRESes) that drive cap-independent translation in part via interactions with ribosome expansion segments. However, the direct functional significance of such interactions has not yet been definitively demonstrated. We provide evidence that the putative IRESes previously reported in Hox gene hTLs are rarely included in transcript leaders. Instead, these regions function independently as transcriptional promoters. In addition, we find the proposed RNA structure of the putative Hoxa9 IRES is not conserved. Instead, sequences previously shown to be essential for putative IRES activity encode a hyperconserved transcription factor binding site (E-box) that contributes to its promoter activity by binding to the transcription factors USF1 and USF2. Similar E-box sequences enhance the promoter activities of other putative Hoxa gene IRESes. Moreover, we provide evidence that the vast majority of hTLs with putative IRES activity overlap transcriptional promoters, enhancers, and 3’ splice sites that are most likely responsible for their reported IRES activities. These results argue strongly against recently reported widespread IRES-like activities from hTLs and contradict proposed interactions between ribosomal expansion segment ES9S and putative IRESes. Furthermore, our work underscores the importance of accurate transcript annotations, controls in bicistronic reporter assays, and the power of synthesizing publicly available data from multiple sources.
Assessing Quantitative MRI Techniques using Multimodal Comparisons
Authors: Carter Francis , Anwander Alfred , Goucha Thomás , Adamson Helyne , Friederici Angela D. , Lutti Antoine , Gauthier Claudine J , Weiskopf Nikolaus , Bazin Pierre-Louis , Steele Christopher J
Published: February 2022

The study of brain structure and change in neuroscience is commonly conducted using macroscopic morphological measures of the brain such as regional volume or cortical thickness, providing little insight into the microstructure and physiology of the brain. In contrast, quantitative MRI allows the monitoring of microscopic brain change non-invasively in-vivo, and provides normative values for comparisons between tissues, regions, and individuals. To support the development and common use of qMRI for cognitive neuroscience, we analysed a set of qMRI metrics (R1, R2*, Magnetization Transfer saturation, Proton Density saturation, Fractional Anisotropy, Mean Diffusivity) in 101 healthy young adults. Here we provide a comprehensive descriptive analysis of these metrics and their linear relationships to each other in grey and white matter to develop a more complete understanding of the relationship to tissue microstructure. Furthermore, we provide evidence that combinations of metrics may uncover informative gradients across the brain by showing that lower variance components of PCA may be used to identify cortical gradients otherwise hidden within individual metrics. We discuss these results within the context of microstructural and physiological neuroscience research.
CD8 T Cell Memory Inflation is Driven by Latent CMV Infection of Lymphatic Endothelial Cells
Authors: Munks Michael W. , Rott Katherine , Nesterenko Pavlo A. , Smart Savannah M. , Williams Venasha , Tatum Angela , Xu George , Smith Tameka , Murray Susan E. , Hill Ann B.
Published: February 2022

CMV, a ubiquitous herpesvirus, elicits an extraordinarily large T cell response that is sustained or increases over time, a phenomenon termed ‘memory inflation.’ Remarkably, even latent, non-productive infection can drive memory inflation. Despite intense research on this phenomenon, the infected cell type(s) involved are unknown. To identify the responsible cell type(s), we designed a Cre-lox murine CMV (MCMV) system, where a spread-deficient (ΔgL) virus expresses recombinant SIINFEKL only in Cre+ host cells. We found that latent infection of endothelial cells (ECs), but not dendritic cells (DCs) or hepatocytes, was sufficient to drive CD8 T cell memory inflation. Infection of Lyve-1-Cre and Prox1-CreERT2 mice revealed that amongst EC subsets, infection of lymphatic ECs was sufficient. Genetic ablation of β2m on lymphatic ECs did not prevent inflation, suggesting another unidentified cell type can also present antigen to CD8 T cells during latency. This novel system definitively shows that antigen presentation by lymphatic ECs drives robust CD8 T cell memory inflation.

Active T cell immunosurveillance during latent CMV infection results in T cell ‘memory inflation.’ A novel Cre-lox genetic system for cell-specific antigen expression reveals that lymphatic ECs, but not DCs or hepatocytes, can drive CD8 T cell memory inflation.
Targeting NAAA counters dopamine neuron loss and symptom progression in mouse models of Parkinson’s disease
Authors: Palese Francesca , Pontis Silvia , Realini Natalia , Torrens Alexa , Ahmed Faizy , Assogna Francesca , Pellicano Clelia , Bossù Paola , Spalletta Gianfranco , Green Kim , Piomelli Daniele
Published: February 2022

The lysosomal cysteine hydrolase N-acylethanolamine acid amidase (NAAA) deactivates the lipidderived mediator palmitoylethanolamide (PEA), an endogenous PPAR-α agonist that is critically involved in the control of inflammation and nociception. In this study, we asked whether NAAA-regulated PEA signaling might contribute to the pathogenesis of Parkinson’s disease (PD), a neurodegenerative disorder characterized by progressive loss of nigrostriatal dopamine neurons. Analyses of postmortem brain cortex and premortem blood-derived exosomes found elevated levels of NAAA expression in persons with PD compared to age-matched controls. Furthermore, in vitro experiments showed that the dopaminergic neurotoxins, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), enhanced NAAA expression and lowered PEA content in human SH-SY5Y cells. A similar effect was observed in dopamine neurons and, subsequently, in microglia following 6-OHDA injection in mice. Importantly, deletion of the Naaa gene or pharmacological inhibition of NAAA activity markedly attenuated both dopamine neuron death and parkinsonian symptoms in mice treated with 6-OHDA or MPTP. The results identify NAAA-regulated PEA signaling as a control node for dopaminergic neuron survival and a potential target for therapeutic intervention in PD.