bluuebunny/crossref_metadata_2025 huggingface dataset:
RdRp-based sensitive taxonomic classification of RNA viruses for metagenomic data
Authors: Tang Xubo , Shang Jiayu , Sun Yanni
Published: January 2022

With advances in library construction protocols and next-generation sequencing technologies, viral metagenomic sequencing has become the major source for novel virus discovery. Conducting taxonomic classification for metagenomic data is an important means to characterize the viral composition in the underlying samples. However, RNA viruses are abundant and highly diverse, jeopardizing the sensitivity of comparison-based classification methods. To improve the sensitivity of read-level taxonomic classification, we developed an RNA-dependent RNA polymerase (RdRp) gene-based read classification tool RdRpBin. It combines alignment-based strategy with machine learning models in order to fully exploit the sequence properties of RdRp. We tested our method and compared its performance with the state-of-the-art tools on the simulated and real sequencing data. RdRpBin competes favorably with all. In particular, when the query RNA viruses share low sequence similarity with the known viruses ($\sim 0.4$), our tool can still maintain a higher F-score than the state-of-the-art tools. The experimental results on real data also showed that RdRpBin can classify more RNA viral reads with a relatively low false-positive rate. Thus, RdRpBin can be utilized to classify novel and diverged RNA viruses.
Feasibility of discharge within 72 hours of major colorectal surgery: lessons learned after 5 years of institutional experience with the ERAS protocol
Authors: Biondi Alberto , Mele Maria Cristina , Agnes Annamaria , Lorenzon Laura , Cintoni Marco , Rinninella Emanuele , Marincola Giuseppe , D’Ugo Domenico , Gasbarrini Antonio , Persiani Roberto
Published: January 2022

Background

Early postoperative discharge after colorectal surgery within the enhanced recovery after surgery (ERAS) guidelines has been demonstrated to be safe, although its applicability has not been universal. The primary aim of this study was to identify the predictors of early discharge and readiness for discharge in a study population.

Methods

Early discharge was defined as discharge occurring in 72 h or less after surgery. The characteristics and clinical outcomes of the patients in the early and non-early discharge groups were compared, and variables associated with early discharge were identified. Additionally, independent variables associated with the readiness for discharge within 48 h were evaluated.

Results

Of 965 patients who underwent colorectal surgery between January 2015 and July 2020, 788 were included in this study. No differences in readmission, reoperation, or 30-day mortality were observed between the early and non-early discharge groups. Both early discharge and readiness for discharge had a positive association with adherence to 80 per cent or more of the ERAS items and a negative association with the female sex, duration of surgery, drain positioning, and postoperative complications.

Conclusion

Early discharge after colorectal surgery is safe and feasible, and is not associated with a high risk of readmission or reoperation. Discharge at 48 h can be reliably predicted in a subset of patients. Future studies should collect prospective data on early discharge related to safety, as well as patients’ expectations, possible organizational issues, and effective costs reduction in Italian clinical practice.
The Development and Validation of Anti-paratuberculosis-nocardia Polypeptide Antibody [Anti-pTNP] for the Diagnosis of Crohn’s Disease
Authors: Gao Han , He Qiong , Xu Chunjin , Pang Zhi , Feng Baisui , Chen Tingting , Yang Wu , Zhou Guangxi , Wang Yufang , Li Junxiang , Su Jingling , Miao Yinglei , Zhao Ye , Liao Zhuan , Xu Can , Liu Zhanju
Published: January 2022

Background and Aims

Non-invasive biomarkers in sera of patients with inflammatory bowel disease [IBD] are not currently available for rapidly and accurately diagnosing the disease. We aimed to investigate and validate the potential roles of anti-paratuberculosis-nocardia polypeptide antibodies [anti-pTNP] in the diagnosis of IBD.

Methods

Serum samples were collected from 502 patients with diagnosed Crohn’s disease [CD], 141 patients with ulcerative colitis [UC], and 109 healthy donors. The levels of anti-pTNPs and anti-Saccharomyces cerevisiae antibodies [ASCAs] were determined by enzyme-linked immunosorbent assay. The effects of each variable on the diagnosis were analysed by receiver operating characteristic [ROC] analysis. We also performed an estimate study by first developing a clinical prediction model, with external validation in CD patients from nine IBD medical centres in China.

Results

The levels of anti-pTNPs in sera of CD patients were higher than those in UC patients and healthy donors. The positive rates of anti-pTNPs were significantly higher in ileal CD patients than in ileocolonic and colonic CD patients, and the levels of anti-pTNP IgG in perianal patients were significantly higher than those in non-perianal CD patients. Of note, anti-pTNPs and perianal diseases were important predictors for active stage of CD patients. Discriminative ability to predict active CD patients was 0.918 (95% confidence interval [CI]:0.886–0.949).

Conclusions

Anti-pTNP functions as a novel biological marker for diagnosing CD and can be used to assess disease severity, particularly in those with lesion locations in the terminal ileum and stricturing and perianal diseases. A validated prediction model reveals that anti-pTNPs are useful for estimating the likelihood of active CD.
A transatlantic battle of the robes: French priests in the Haitian Revolution
Authors: Franchina Miriam
Published: January 2022

In line with reconsiderations of the importance of religion in the Age of Revolutions, this article reconstructs how French priests competed to gain control of the Church in revolutionary Saint-Domingue and navigated the ever-changing political landscapes triggered by the Haitian and French Revolutions. Priests in the Haitian Revolution were also priests in the French Revolution: divided in their visions of a Church—Gallican and constitutional, or in communion with Rome—and active on both sides of the Atlantic. Priests’ motives for cooperating with the enslaved insurgents between 1791 and 1793, and with the free cultivateurs thereafter, are here contextualized within the ongoing frictions between Rome and Paris. Their experiences offer a fruitful means to gauge the entanglements between the French and Haitian Revolution, and suggest how some Haitian revolutionaries—Louverture and King Christophe, for instance—turned to Rome as an alternative to France as a source of political legitimacy.
Impact of a guaranteed minimum income program on rural–urban migration in China
Authors: Howell Anthony
Published: January 2022

This article relies on a regression discontinuity (RD) design to estimate the impact of an unconditional cash transfer from Minimum Income Living Allowance (MLSA)—one of the largest basic income guarantee programs in the world—on the household decision to participate in rural–urban migration. The study is informed by novel survey data that provide the first and only representative information on China’s large, but understudied ethnic minority areas. Exploiting the income-based MLSA eligibility rule as an instrument, fuzzy RD estimates reveal that MLSA subsidy receipt significantly increases the likelihood that complier households participate in rural–urban migration, a finding that is robust to a batter of sensitivity tests and checks for robustness. In line with the idea that MLSA cash subsidies help to loosen household credit or risk constraints, I show that the observed positive effects are driven mainly by poor [ethnic minority] households that face relatively high perceived migration costs. Additional evidence shows that the MLSA program increases complier households’ disposable income and consumption despite having no significant effect on household investment behavior. The main findings suggest that a small cash infusion from a minimum income program like MLSA helps to promote migration-led urbanization and rural household wellbeing.
A pancreatic mass and extreme elevation of CA 19–9: a benign masquerade of cholangiocarcinoma
Authors: Hall Catherine , McLaren Mairi , Mosse Charles
Published: January 2022

Carbohydrate antigen 19–9 (CA 19–9) is a specific tumour marker for pancreato-biliary malignancy. Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition in which IgG4 deposits infiltrate various organs, including the biliary tract manifesting IgG4 sclerosing cholangitis and pseudotumours. An 83-year-old woman presented with severe obstructive jaundice, weight loss and an extreme elevation of CA 19–9 level of 3295 kU/L. Magnetic resonance cholangiopancreatography (MRCP) revealed a pancreatic mass amputating the biliary tree. Liver function tests revealed a cholestatic pattern and severe hyperbilirubinaemia (289umol/L). IgG4 level was found to be high at 7.97 g/L. After treatment with high-dose corticosteroids, repeat MRCP 2 months later revealed disappearance of the pancreatic mass. There was also normalization of the bilirubin and a dramatic decrease of CA 19–9. This case reports the highest published benign elevation of Ca19.9 level in the setting of IgG4 disease. Differentiation between cholangiocarcinoma and IgG4-RD is important, as the treatment is vastly different.
Multimodality Imaging Assessment of Anomalous Aortic Origin of the Left Main Coronary Artery Presenting With Syncope and Non-ST Elevation Myocardial Infarction
Authors: Cho Jonathan J , Fabrizio Samantha D , Tabing Ariana K , Boswell Gilbert E , Condos Gregory J
Published: January 2022

Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital abnormality associated with myocardial ischemia and sudden cardiac death. We present a case of a 20 year old previously healthy male presenting with exertional syncope and non-ST elevation myocardial infarction. Coronary computed tomography angiography showed an anomalous left main coronary artery arising from the right coronary cusp with a slit-like appearance, acute angle origin, intramural course, and a subsequent inter-arterial course between the main pulmonary artery and the proximal aorta. Cardiac magnetic resonance imaging demonstrated myocardial infarction in the distribution of the left main coronary artery. The patient underwent successful surgical correction with unroofing of the left main coronary artery. He has had no syncopal episodes or recurrence of chest pain and returned to full duty status in the United States Marine Corps. This case report demonstrates the evaluation and management of a patient with AAOCA.
Ibn ‘Arabī and Kafka on God and the Law
Authors: Lala Ismail
Published: January 2022

Although ostensibly different, Franz Kafka and the mystical theorist Muḥyī al-Dīn ibn ‘Arabī (d. 638/1240) both employ complex rhetoricity that accommodates paradox and contradiction. This study compares how their complex rhetoricity exposes the tension between the essential human need to comprehend god, and a god who is essentially apophatic. God’s apophasis, expressed as His numinous laws, inevitably comes into conflict with Man’s rationality. Through a theological/legal analysis of Kafka’s novel, The Trial, and ‘Ibn ‘Arabī’s interpretation of ‘Īsā’s (Jesus’) encounter with God on the Day of Judgement, the implications of this tension are explored. Manifested as the incompatibility of immutable divine laws and variable human affairs, and the divergent demands of the individual and the community, the epistemic crisis elicited by this tension provokes opposing reactions from Kafka’s protagonist, Josef K., and ‘Īsā. Josef K.’s demise results from his exclusive reliance on reason, while Īsā succeeds in his encounter with God because he recognizes that, even though rationality is necessary, it is limited.
Negative string tension of a higher-charge Schwinger model via digital quantum simulation
Authors: Honda Masazumi , Itou Etsuko , Kikuchi Yuta , Tanizaki Yuya
Published: January 2022

We study some properties of generalized global symmetry for the charge-q Schwinger model in the Hamiltonian formalism, which is the (1 + 1)D quantum electrodynamics with a charge-q Dirac fermion. This model has the $\mathbb {Z}_q\, 1$-form symmetry, which is a remnant of the electric $U(1)\, 1$-form symmetry in the pure Maxwell theory. It is known that, if we put the theory on closed space, then the Hilbert space is decomposed into q distinct sectors, called universes, and some states with higher energy density do not decay to the ground state due to the selection rule of the 1-form symmetry. Even with open boundaries, we can observe the stability of such states by seeing a negative string tension behavior, meaning that opposite charges repel each other. In order to see negative string tensions, the vacuum angle θ has to be large enough and the standard path-integral Monte Carlo method suffers from the sign problem. We develop a method based on the adiabatic state preparation to see this feature with digital quantum simulation and confirm it using a classical simulator of quantum devices. In particular, we measure the local energy density and see how it jumps between the inside and outside of the insertion of the probe charges. We explicitly see that the energy density inside is lower than that outside. This is a clear signature of the negative string tension.
On the parameterisation of a class of doubly periodic lattices of equally strong holes
Authors: Marshall J S
Published: January 2022

We construct an exact, explicit parameterisation of a class of doubly periodic lattices of equally strong holes in an infinite elastic plate that is in a state of plane stress. This parameterisation assumes no symmetries of the lattices’ holes and allows for any finite number of holes per period cell. It is stated in terms of a conformal map from a circular domain. We construct this map in terms of the integrals of the first kind that are associated with a Schottky group that is generated from this circular domain. Key to our derivation of this parameterisation is the observation that a doubly periodic lattice of equally strong holes is characterised by the property that the Schwarz functions of all of its holes’ boundaries are identical up to additive constants. We also conjecture a condition that is necessary and sufficient for the existence of the class of lattices that are described by this parameterisation, although we are only able to verify this condition numerically here. We also present a selection of examples of such lattices, computed using this parameterisation.
Experiences with Medicaid Renewal and Reauthorization Policies in the Context of Child Health and Vaccine Coverage
Authors: Holroyd Taylor A , Oloko Oladeji K , Limaye Rupali J
Published: January 2022

Difficulties complying with Medicaid recertification requirements may be responsible for a portion of Medicaid disenrollments and may impact access to preventive care. This study aimed to explore the barriers parents experienced renewing their child’s Medicaid, how those barriers impact access to healthcare, and how changes in Medicaid policy can improve child health outcomes. To understand the barriers associated with Medicaid renewal, authors conducted in-depth interviews (N = 24) with racially and demographically diverse parents living in Baltimore. They found that administrative burden, lack of awareness regarding reauthorization, challenges with navigation assistance, and lack of access to the renewal system were crucial barriers to renewing Medicaid. Many participants identified negative impacts on child health outcomes resulting from lapses in coverage, including lack of healthcare access and missed immunizations. Drawing on these findings, the authors provide recommendations for streamlining and clarifying the Medicaid renewal process in Maryland, and the role of social work policy and practice in reducing barriers to renewal.
Secular Trend in the Incidence of Conduct Disorder in China from 1990 to 2019: A Joinpoint and Age-Period-Cohort Analysis
Authors: Wang Yufeng , Huang Xueying , Li Shasha , Yue Suru , Liu Jie , Wu Jiayuan
Published: January 2022

Objective:

The aim of this study was to analyze the secular trends of conduct disorder (CD) incidence in China from 1990 to 2019 under the joinpoint analysis and the age-period-cohort framework.

Methods:

The sex-specific incidence rates of CD from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database according to the age group. The joinpoint regression and the age-period-cohort model were conducted using the average annual percent changes and relative risks as size effects, respectively.

Results:

From 1990 to 2019, age-standardized rates (ASRs) of CD incidence showed an overall increasing trend in both sexes, and this variation trend was observed in almost all age groups. The annual sex-specific ASRs were lower in China than those worldwide but were rapidly growing. Age effects were the most significant risk factor for CD, with the highest risk in adolescents aged 10 to 14 years, followed by children aged 5 to 9 years, but a relatively lower risk in adolescents aged 15 to 19 years than in other age groups. However, period and cohort effects were not statistically significant.

Conclusion:

CD incidence rates in China have been increasing in both sexes from 1990 to 2019. Further studies are necessary to explain the etiology of these increases and promote the early identification of individuals at risk for developing CD.
Azacitidine maintenance in AML post induction and posttransplant
Authors: Bewersdorf Jan Philipp , Prebet Thomas , Gowda Lohith
Published: January 2022

Purpose of review

Disease relapse remains the most common cause of death among patients with acute myeloid leukemia (AML) following induction therapy and allogeneic hematopoietic cell transplant (allo-HCT). Prolonging the duration of remission with minimal nonrelapse mortality risk is an area of unmet need for AML patients.

Recent findings

In QUAZAR AML-001 study, the oral azacitidine analogue CC-486 demonstrated an overall survival (OS) benefit when given as postremission therapy (PRT) for patients in CR1 that were ineligible to proceed to allo-HCT. Used as maintenance post allo-HCT, CC-486 has also shown safety with encouraging disease-free survival (DFS). Although a recent randomized trial of parenteral azacitidine vs. placebo post allo-HCT failed to show relapse reduction, a subsequent meta-analysis of maintenance studies posttransplant has shown good utility with this approach. Such conflicting results emphasize the need for robust study designs to identify subsets of patients that derive maximal benefits using latest tools to risk stratify relapse risk.

PRT with hypomethylating agents is feasible and in select population, there is a survival advantage with CC-486. Better understanding of distinct epigenetic and immunomodulatory properties of azacitidine, holds significant promise to synergize pharmacologic and cellular drivers of disease control as PRT in future AML trials.
A novel prediction model to evaluate the probability of CD4+/CD8+ cell ratio restoration in HIV-infected individuals
Authors: Li Bei , Zhang Leidan , Liu Ying , Xiao Jing , Li Cuilin , Fan Lina , Duan Yujiao , Xiao Jiang , Hao Yu , Han Junyan , Kong Yaxian , Zhao Hongxin
Published: January 2022

Background:

Our study aimed to develop a clinical prediction model to evaluate the possibility of CD4+/CD8+ ratio restoration in HIV-positive individuals.

Methods:

About 1980, HIV/AIDS patients initiated with antiretroviral treatment from 1 January 2013, to 30 December 2016, at Beijing Ditan Hospital and achieved persistent virological suppression during the 4 years follow-up were included in this study. Multivariate Cox proportional regression analysis was used to identify the independent risk factors and establish a predictive model. The model's performance was assessed using the area under the receiver operating characteristic and calibration plots.

Results:

Overall, after 4 years of treatment, a total of 455 individuals (22.98%) restored their CD4+/CD8+ ratio (≥1). The area under the receiver operating characteristic was 0.782 and 0.743 in the deriving and validation cohort, respectively. The ultimate model included five indexes: age at AIDS diagnosis, albumin, and syphilis status, and baseline CD4+ and CD8+ values. A nomogram further visualized the model, and the calibration plots indicated high agreement of predicted and observed outcomes.

Conclusion:

Our prediction model might be practical and easily applied to recognize HIV/AIDS individuals most likely to benefit from modern antiretroviral therapy.
Aging, trends in CD4+/CD8+ cell ratio, and clinical outcomes with persistent HIV suppression in a dynamic cohort of ambulatory HIV patients
Authors: Novak Richard M. , Armon Carl , Battalora Linda , Buchacz Kate , Li Jun , Ward Douglas , Carlson Kimberly , Palella Frank J.
Published: January 2022

Background:

Age blunts CD4+ lymphocyte cell count/μl (CD4+) improvements observed with antiretroviral therapy (ART)-induced viral suppression among people with HIV (PWH). Prolonged viral suppression reduces immune dysregulation, reflected by rising CD4+/CD8+ ratios (CD4+/CD8+). We studied CD4+/CD8+ over time to determine whether it predicts risk for select comorbidities and mortality among aging PWH with viral suppression.

Methods:

We studied HIV Outpatient Study (HOPS) participants prescribed ART during 2000–2018 who achieved a viral load less than 200 copies/ml on or after 1 January 2000, and remained virally suppressed at least 1 year thereafter. We modeled associations of CD4+/CD8+ with select incident comorbidities and all-cause mortality using Cox regression and controlling for demographic and clinical factors.

Results:

Of 2480 eligible participants,1145 (46%) were aged less than 40 years, 835 (34%) 40–49 years, and 500 (20%) ≥ 50 years. At baseline, median CD4+/CD8+ was 0.53 (interquartile range: 0.30–0.84) and similar among all age groups (P = 0.18). CD4+/CD8+ values and percentage of participants with CD4+/CD8+ at least 0.70 increased within each age group (P < 0.001 for all). CD4+/CD8+ increase was greatest for PWH aged less than 40 years at baseline. In adjusted models, most recent CD4+/CD8+less than 1.00 and less than 0.70 were independently associated with higher risk of non-AIDS cancer and mortality, respectively.

Conclusion:

Pretreatment immune dysregulation may persist as indicated by CD4+/CD8+ less than 0.70. Persistent viral suppression can improve immune dysregulation over time, reducing comorbidity, and mortality risk. Monitoring CD4+/CD8+ among ART-treated PWH with lower values provide a means to assess for mortality and comorbidity risk.
Chronic HIV Infection and Aging: Application of a Geroscience-Guided Approach
Authors: Masters Mary C. , Landay Alan L. , Robbins Paul D. , Tchkonia Tamar , Kirkland James L. , Kuchel George A. , Niedernhofer Laura J. , Palella Frank J.
Published: January 2022

The ability of virally suppressive antiretroviral therapy use to extend the life span of people with HIV (PWH) implies that the age of PWH will also increase. Among PWH, extended survival comes at a cost of earlier onset and increased rates of aging-associated comorbidities and geriatric syndromes, with persistent inflammation and immune dysregulation consequent to chronic HIV infection and to antiretroviral therapy use contributing to an overall decrease in health span. The geroscience hypothesis proposes that the root causes of most aging-related chronic diseases and conditions is the aging process itself. Hence, therapeutically targeting fundamental aging processes could have a greater impact on alleviating or delaying aging-associated comorbidities than addressing each disease individually. Extending the geroscience hypothesis to PWH, we speculate that targeting basic mechanisms of aging will improve overall health with age. Clinical features and pathophysiologic mechanisms of chronic diseases in PWH qualitatively resemble those seen in older adults without HIV. Therefore, drugs that target any of the pillars of aging, including metformin, rapamycin, and nicotinamide adenine dinucleotide precursors, may also slow the rate of onset of age-associated comorbidities and geriatric syndromes in PWH. Drugs that selectively induce apoptosis of senescent cells, termed senolytics, may also improve health span among PWH. Preliminary evidence suggests that senescent cell burden is increased in PWH, implying that senescent cells are an excellent therapeutic target for extending health span. Recently initiated clinical trials evaluating senolytics in age-related diseases offer insights into the design and potential implementation of similar trials for PWH.
Distinct Molecular Signatures of Aging in Healthy and HIV-Infected Individuals
Authors: Rinaldi Stefano , Pallikkuth Suresh , De Armas Lesley , Richardson Brian , Pan Li , Pahwa Rajendra , Williams Sion , Cameron Mark , Pahwa Savita
Published: January 2022

Background:

Virally suppressed chronic HIV-infected individuals on antiretroviral therapy experience similar immune impairments as HIV-uninfected elderly. However, they manifest symptoms of premature immune aging such as suboptimal responses to vaccination at a younger age. Mechanisms underlying premature immune aging are unclear.

Setting:

The study site was University of Miami Miller School of Medicine.

Methods:

In this study, we aimed to identify molecular signatures of aging in HIV-infected (HIV) individuals compared with age-matched healthy control (HC) participants. Transcriptomic profiles of peripheral blood mononuclear cells collected cross-sectionally from study participants were evaluated using RNA sequencing, and genes and pathways associated with age and HIV status were identified and compared between study groups. Generalized linear modeling was used to identify transcriptional signatures associated with age.

Results:

Despite that fewer differentially expressed genes between young (<40 yrs) and old (>59 yrs) were observed in the HIV group, metabolic and innate immune activation pathways were associated with increasing age in both HIV and HC. Age was also associated with pathways involved with T-cell immune activation in HC and with interferon signaling pathways in HIV. We observed signs of precocious immune aging at the transcriptional level in HIV and defined a transcriptional perturbation associated with innate immunity and glucose metabolism induced by aging in both HC and HIV.

Conclusion:

In this study, we identified distinct molecular signatures predictive of age in HIV versus HC, which suggest precocious immune aging in HIV. Overall, our results highlight the molecular pathways of immune aging in both HC and HIV that may be targeted for additional mechanistic insights or in a therapeutic setting.
Resilience and Frailty in People Living With HIV During the COVID Era: Two Complementary Constructs Associated With Health-Related Quality of Life
Authors: Guaraldi Giovanni , Milic Jovana , Barbieri Sara , Marchiò Tommaso , Caselgrandi Agnese , Volpi Sara , Aprile Emanuele , Belli Michela , Venuta Maria , Mussini Cristina
Published: January 2022

Background:

Resilience is defined as an individual's positive adaptation to stressors. The COVID-19 pandemic represents a generalized stressor which may affect differently people living with HIV (PLWH). The objective of this study was to characterize resilience in PLWH with particular regarding the identification of frailty-resilience phenotypes, which may differently affect health-related quality of life (HR-QoL).

Methods:

This was an observational study of PLWH attending Modena HIV Metabolic Clinic. Frailty was assessed in 2019, before the onset of the COVID-19 pandemic by using 37-Item frailty index ranging from 0 to 1. The frailty index score was categorized as fit (<0.25) or frail (>0.25). In January 2021, PLWH were offered to complete a set of electronic questionnaires including the CD-RISC-25 for resilience and EQ-5D5L and SF-36 for HR-QoL. Resilience was defined as CD-RISC-25 score >75.7 (ranging from 0 to 100).

Results:

Of 800 PLWH reached by mail, 575 (72%) completed the questionnaires. The median age and HIV duration were 54.5 and 24.3 years, respectively. Impaired resilience was associated with loneliness [odds ratio (OR = 2.39; 1.20 to 4.76, P < 0.001)]. Predictors for EQ-5D5L <89.7% were the phenotypes “frail/nonresilient” [OR = 5.21, 95% confidence interval (CI): 2.62 to 10.33] and “fit/nonresilient” (OR = 5.48, 95% CI: 2.8 to 10.74). Predictors for SF-36 <64.40 were the phenotypes “frail/nonresilient” (OR = 7.43, 95% CI: 2.57 to 21.22) and “fit/nonresilient” (OR = 6.27, 95% CI: 2.17 to 18.16). Both models were corrected for age, sex, HIV duration, and nadir CD4.

Conclusions:

Resilience characterizes the well-being of PLWH during the COVID-19 crisis. This construct is complementary to frailty in the identification of clinical phenotypes with different impacts on HR-QoL.
Quantification of CD4 Recovery in Early-Treated Infants Living With HIV
Authors: Schröter Juliane , Anelone Anet J. N. , de Boer Rob J.
Published: January 2022

Background:

Perinatally HIV-acquired infants benefit from an early antiretroviral treatment initiation. Thanks to a short viral exposure time, their immune system can be maintained or reconstituted, allowing a “normal” immune development.

Methods:

In this study, we mathematically modeled and quantified individual CD4+ T-cell reconstitution of a subset of 276 children who started treatment within 6 months of age and achieved sustained viral suppression. Considering natural age differences in CD4+ T-cell dynamics, we fitted distances to age-matched healthy reference values with a linear model approaching an asymptote.

Results:

Depleted CD4+ percentages (CD4%) and CD4+ counts (CD4ct) restored healthy levels during treatment. CD4ct recovered with a median rate of 4 cells/µL/d, and individual recovery rates were correlated negatively with their initial CD4ct. CD4 values at onset of treatment decrease with age, whereas recovery times and levels seem to be age-independent. CD4 recovery correlates positively with viral suppression, and the stabilization of CD4 levels usually occurs after viral suppression. CD4 levels stabilize within 3–13 months after treatment initiation. The recovery dynamics of the CD4% is comparable with those of the CD4ct.

Conclusions:

In early-treated children with successful viral suppression, the CD4 depletion is typically mild and CD4+ T cells tend to “fully” recover in numbers.
Evaluation of a Public Health Referral System to Re-Engage Individuals Living With HIV Who Have Interrupted Antiretroviral Therapy in British Columbia, Canada
Authors: Moore David M. , Kremer Hayden , Wang Lu , Lepik Katherine J. , Li Jenny , Salters Kate , Montaner Julio S. G. , Tam Clara , Kling Rakel , Bharmal Aamir , Goodison Karin , Pakhomova Tatiana , Barrios Rolando
Published: January 2022

Background:

In 2016, the British Columbia HIV/AIDS Drug Treatment Program modified its prescriber alert system for antiretroviral therapy (ART) interruptions to include referrals to regional public health nursing teams for direct outreach support for those who remain off treatment for 4 months or longer. We evaluated clinically relevant outcomes of this Re-Engagement and Engagement in Treatment for Antiretroviral Interrupted and Naïve populations (RETAIN) initiative, in comparison to previous time-periods.

Methods:

We analyzed ART interruptions triggering alerts in pre-RETAIN (July 2013-April 2016) and post-RETAIN periods (May 2016–October 2017) with follow-up continuing until October 2018. We compared the proportions of those who restarted ART and achieved viral suppression in pre-RETAIN and post-RETAIN periods and the time to ART restart using generalized estimating equations. Cox proportional hazards modelling was used to examine associations with time-to-ART-restart.

Results:

A total of 1805 individuals experienced ART interruptions triggering 3219 alerts; 2050 in pre-RETAIN and 1169 in post-RETAIN periods. Participants were predominantly men (74%) and had a median duration of ART of 5 years. Among persons who remained interrupted >4 months after an ART interruption alert was sent, the median time from interruption to ART re-initiation declined from 8.7 months to 7.4 months (P < 0.001) from pre-to post-RETAIN periods. Interruptions in the post-RETAIN era were associated with an increased hazard of restarting ART (adjusted hazard ratio 1.51; 95% CI: 1.34 to 1.69).

Conclusions:

Public health referrals shortened the length of ART interruptions after alerts sent to prescribers had not resulted in re-engagement. Similar programs should be considered in other jurisdictions.
Simultaneous extraction of proteins and carbohydrates, including
phenolics, antioxidants, and macamide B from Peruvian maca (Lepidium
meyenii Walp.)
Authors: You Ji Young , Joung Ji An , Baek Seo Jun , Chen Jinlong , Choi Joon Ho
Published: January 2022

Maca (Lepidium meyenii Walp.) has been used for nutritional and
traditional purposes, owing to its chemical composition and the presence of
bioactive compounds. This study aimed to develop and optimize a maceration-based
method for the simultaneous extraction of total phenolic compounds (TPCs), total
flavonoids (TFs), radical-scavenging activity (RSA), soluble proteins (SPs),
total sugars (TSs), reducing sugars (RSs), and macamide B from maca using 95%
ethanol and acidified ethanol. The effects of extraction parameters, including
temperature, solvent-to-solid ratio, time, and acid concentration, on the
extraction yield of TPCs, TFs, RSA, SPs, TSs, RSs, and macamide B were
investigated. Optimal extraction was achieved at 40-60°C for 5-7.5 h with
the solvent-to-solid ratio of 100:10. The addition of hydrochloric acid (HCl) to
ethanol significantly improved the extraction yield, and maximum extraction was
achieved using 1 N HCl in ethanol. The RSA of the ethanolic extracts showed a
significant linear correlation (p<0.001) with total extraction yield,
TPCs, SPs, and TSs. These results imply that polyphenolic compounds,
SPs/peptides, and polysaccharides are important determinants for the antioxidant
function of maca. The optimized condition may be employed in nutraceutical
industries to extract bioactive compounds from maca.
Physicochemical and sensory properties of hamburger steak made with
venison
Authors: Lee Nan-Hee , Choi Ung-Kyu
Published: January 2022

Industrial production of processed meat products using venison requires
optimization of quality attributes. In this study, physicochemical and sensory
properties of hamburger steaks made with venison were evaluated. The crude
protein content increased significantly but the crude fat content decteased in
proportion to the venison content. The saturated fatty acid content increased as
the venison content increased. Both monounsaturated fatty acids and
polyunsaturated fatty acids decreased with increasing venison contents. The
oleic acid content was the highest, followed by palmitic acid, stearic acid, and
linoleic acid. The free amino acid content increased in proportion to the amount
of venison added. The most abundant amino acids in the three types of steaks
were alanine, glutamic acid, glycine and leucine. In result of sensory
evaluation, the preference for hamburger steak made with 100% venison was
relatively high among samples except flavor. This results confirmed that the
sensory properties of hamburger steak made with venison are superior to those of
pork, and thus industrialized venison production is promising.
Nutritional components and physiological activities of
Petasites japonicus solvent extracts
Authors: Eom Hyun-Ju , Shin Hyun Young , Jeong Yu Yeong , Kwon Nu Ri , Kim Ki Hyun , Kim In Jae , Yu Kwang-Won
Published: January 2022

Petasites japonicus (PJ) has been used traditionally as the
treatment or the prophylaxis of migraine and tension headache in Asia. In the
present study, to we compared the characteristics of PJ powder and extracts
obtained by various methods utilize the PJ as a functional material. PJ powder
by freeze-drying possessed 6.61% water content, 4.51% crude fat, 23.75% crude
protein, 18.62% crude ash, 46.97% carbohydrates, and crude fiber 39.22%. It
contained a particularly high potassium content in mineral. Among different
extraction methods, extracts of 50% (PJ-50E) or 70% ethanol (PJ-70E) showed the
highest total polyphenol content and antioxidant activity, while cold-water
extraction (PJ-WE) showed the lowest. However, when the α-glucosidase
inhibitory were analyzed, PJ-WE was highest while the treatment extracted
ethanol were not active at all. In anti-inflammatory activity by RAW 264.7 and
HaCaT cells, PJ-WE showed significantly higher inhibitory activity in comparison
to those of the other extract. In conclusion, it is considered that the
water-extraction method is better than other extraction methods for practical
preparation of functional materials with high α-glucosidase inhibitory
and anti-inflammatory activities from PJ.
Effect of grain raw materials on the quality characteristics of
‘Kaoliang’ spirit
Authors: Seo Hwa-Rang , Jeong Seok-Tae , Iim Bo-Ra , Kang JI-Eun , Kang Heui-Yun , Yun Sun-Il
Published: January 2022

This study was carried out to investigate the quality characteristics of
‘Kaoliang’ spirit by grain materials for developing the
Korean-style ‘Kaoliang’ spirit. Each grain was crushed for solid
fermentation, and re-fermentation was performed three times in total. There was
no significant difference in temperature during solid fermentation by different
grains, but it rose to up to 31°C until the first two days of
fermentation, and then the fermentation was completed while maintaining
27°C. Agglomeration occurred in solid fermentation using wheat, resulting
in lower work efficiency than other grains. The total acids increased after
fermentation, and was the highest at 0.77% in distilled spirit using sorghum,
and the major organic acids were lactic acid and acetic acid. A lot of glycerol
and glucose were detected, and after three re-fermentation, all sugars were
converted to ethanol. Through three re-fermentation, ethanol was the highest in
distilled spirit using corn and barley. The volatile compounds, ethyl acetate,
ethyl butyrate, and ethyl lactate, were detected at the high level in distilled
spirit using sorghum, and the highest ethyl caproate component in using wheat.
Therefore, this study proposed to use the mixed grain materials, sorghum and
wheat, in order to increase the production of ethyl caproate, the main aroma
compound in ‘Kaoliang’ spirit.
Antioxidant activity and neuroprotective effect of ethyl acetate fraction of Lonicera japonica on H2O2-induced oxidative stress
Authors: Jeong Hye Rin , Kim Jong Min , Kang Jin Yong , Moon Jong Hyun , Kim Min Ji , Lee Hyo Lim , Go Min Ji , Gu Su Yeon , Kim Hyun Jin , Heo Ho Jin
Published: January 2022

Lonicera japonica are commonly used in herbal medicine for the antipyretic, detoxicant and anti-inflammatory actions. In this study, the in vitro antioxidant activity and neuronal protective effects of the ethyl acetate fraction of L. japonica (EFLJ) on H2O2-induced hippocampal HT22 and human neuroblastoma MC-IXC cells were evaluated. The 40% ethanolic extracts of L. japonica showed higher total phenolic and flavonoid contents than those of other ethanolic extracts. EFLJ showed higher 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 1,1-dphenyl-2-picrlhydrazyl (DPPH) radical scavenging activities than those of other fractions. EFLJ exhibited significant antioxidant activity, as determined by ferric reducing/antioxidant power (FRAP) assay, and showed inhibitory effects on malondialdehyde (MDA) production. EFLJ inhibited acetylcholinesterase (AChE) activity. In addition, EFLJ inhibited the production of reactive oxygen species and increased cell viability in H2O2-induced HT22 and MC-IXC cells, as determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and 2’,7’- dichlorofluorescein diacetate (DCF-DA) assays. The main phenolic compounds in EFLJ identified by ultra-high performance liquid chromatography-quadrupole time of flight/mass spectrometry (UPLC-QTOF/MS) were chlorogenic acid, quercetin pentoside, luteolin-7-glucoside, 3,4-dicaffeoylquinic acid, 1,3-dicaffeoylquinic acid and 1,4- dicaffeoylquinic acid. These results suggested that EFLJ includes various compounds with considerable antioxidant activity and neuronal protective effects against oxidative stress-induced cellular cytotoxicity. Therefore, EFLJ is a valuable functional food material for the prevention and improvement of neurodegenerative disorders.
Cognition improving effect of the compositions prepared with extracts of Wongam, Sorghum bicolor (L.) Moench and pupae of Bombyx mori L.
Authors: Lee Seung-Eun , Park Saet-Byul , Kweon Hae-Yong , Park Jeong-Yong , Lee Ji-Yeon , Jo You-Young , Lee Jeonghoon , Jang Gwi-Yeong , Choi Su-Ji , Kim Dong-Hwi
Published: January 2022

Dementia including Alzheimer’s disease, is a severe neurodegenerative disorder characterized by progressive cognitive deficits as major symptom. The compositions (BBGS171) including extracts from root of Wongam (a Glycyrriza cultivar), seed of Sorghum bicolor (L.) pupae of Moench and Bombyx mori L. was selected based on preliminary experiments on the ability to improve cognition function in vitro. BBGS171 showed inhibitory activity on cholinesterases, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuchE) and inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-treated BV2 cells (a microglial cell line). The Y-maze test and passive avoidance test (PAT) were used to evaluate the behavior of an animal model of scopolamine-induced cognitive impairment. Rats administered BBGS171 (EM, extract mixture) in the diet showed better spontaneous alteration and escape latency than those of control rats. Levels of hippocampal choline acetyltransferase (ChAT) and serum acetylcholine (ACh) were significantly higher in the BBGS171 diet group than in the control group. Expression levels of brain-derived neurotrophic factor (BDNF) and extracellular signal-regulated kinase (ERK) 1/2 in the hippocampus of the BBGS171 diet group were also higher than those of control group. These results suggest that BBGS171 (EM) could ameliorate cognition impairment and showed potential as a useful functional material.
“General anxiety and depression are associated with the physical activity and social interaction levels: Study in Argentinean university students during the COVID-19 outbreak”
Authors: Barbuzza Alejo , Benedetti Pedro , Goyeneche Celina , Reppucci Victoria , Moscato Franco , Butavand Daniela Ramirez , Katche Cynthia , Medina Jorge Horacio , Moncada Diego , Viola Haydée , Ballarini Fabricio
Published: January 2022

Background

Due to the coronavirus disease 2019 (COVID-19), the planet is going through a historical time of exceptional concern and uncertainty, which impacts people’s mental health. Here, we explored the levels of depression and Generalized Anxiety Disorder (GAD) and their relation with the degree of physical activity and social interaction during the pandemic.

Methods

We performed a structured survey containing the PHQ-9 and GAD-7 tests to evaluate depressive symptoms and GAD levels. We also asked about weekly physical activity and the level of social interaction. We surveyed two groups of University students in the Buenos Aires Metropolitan Area: an internal group from the Instituto Tecnológico de Buenos Aires (ITBA), and an external group of students from multiple universities. The survey was conducted in late October/early-November 2020, after a peak of contagions. Some of the participants were surveyed again in January 2021, during academic holidays and after a valley of contagion, for longitudinal analysis

Results

Our data show that men and women of both groups exhibited a significant positive linear correlation between depression and GAD levels. Moreover, low levels of depression and anxiety were associated with performing physical activity for more than two days a week and to longer periods of social interaction. Finally, the second survey revealed a decrease of the symptoms.

Conclusions

Our results suggest that performing regular physical activity and avoiding long periods of social isolation gave benefits to mental health. We suggest that public policies could consider protecting these behaviors under health and safety standards.
RelCoVax®, a two antigen subunit protein vaccine candidate against SARS-CoV-2 induces strong immune responses in mice
Authors: Phatarphekar Abhishek , Vidyadhar Reddy G. E. C. , Gokhale Abhiram , Karanam Gopala , Kuchroo Pushpa , Shinde Ketaki , Masand Girish , Pagare Shyam , Khadpe Nilesh , Pai Sangita S. , Vijayan Vijita , Ramnath R. L. , Reddy K. Pratap , Rao Praveen , Rao S. Harinarayana , Ramana Venkata
Published: January 2022

The COVID-19 pandemic has spurred an unprecedented movement to develop safe and effective vaccines against the SARS-CoV-2 virus to immunize the global population. The first set of vaccine candidates that received emergency use authorization targeted the spike (S) glycoprotein of the SARS-CoV-2 virus that enables virus entry into cells via the receptor binding domain (RBD). Recently, multiple variants of SARS-CoV-2 have emerged with mutations in S protein and the ability to evade neutralizing antibodies in vaccinated individuals. We have developed a dual RBD and nucleocapsid (N) subunit protein vaccine candidate named RelCoVax® through heterologous expression in mammalian cells (RBD) and E. coli (N). The RelCoVax® formulation containing a combination of aluminum hydroxide (alum) and a synthetic CpG oligonucleotide as adjuvants elicited high antibody titers against RBD and N proteins in mice after a prime and boost dose regimen administered 2 weeks apart. The vaccine also stimulated cellular immune responses with a potential Th1 bias as evidenced by increased IFN-γ release by splenocytes from immunized mice upon antigen exposure particularly N protein. Finally, the serum of mice immunized with RelCoVax® demonstrated the ability to neutralize two different SARS-CoV-2 viral strains in vitro including the Delta strain that has become dominant in many regions of the world and can evade vaccine induced neutralizing antibodies. These results warrant further evaluation of RelCoVax® through advanced studies and contribute towards enhancing our understanding of multicomponent subunit vaccine candidates against SARS-CoV-2.
RAB18 is a key regulator of GalNAc conjugated siRNA induced silencing in Hep3B cells
Authors: Lu Jiamiao , Swearingen Elissa , Hardy Miki , Collins Patrick , Wu Bin , Yuan Eric , Lu Daniel , Li Chi-Ming , Wang Songli , Ollmann Michael
Published: January 2022

Small interfering RNAs (siRNA) therapeutics have developed rapidly in recent years, despite the challenges associated with delivery of large, highly charged nucleic acids. Delivery of siRNA therapeutics to the liver has been established, with conjugation of siRNA to N-acetylgalactosamine (GalNAc) providing durable gene knockdown in hepatocytes following subcutaneous injection. GalNAc binds the asialoglycoprotein receptor (ASGPR) that is highly expressed on hepatocytes and exploits this scavenger receptor to deliver siRNA across the plasma membrane by endocytosis. However, siRNA needs to access the RNA-induced silencing complex (RISC) in the cytoplasm to provide effective gene knockdown and the entire siRNA delivery process is very inefficient, likely due to steps required for endosomal escape, intracellular trafficking, and stability of siRNA. To reveal the cellular factors limiting delivery of siRNA therapeutics, we performed a pooled, genome wide knockout screen based on delivery of GalNAc conjugated siRNA targeting the HPRT1 gene in the human hepatocellular carcinoma line Hep3B. Our primary pooled genome wide knockout screen identified candidate genes that when knocked out significantly enhanced siRNA efficacy in Hep3B cells. Follow-up studies indicate that knockout of one gene in particular, RAB18, improved siRNA efficacy.