bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontostriatal functional connectivity underlies self-enhancement during social evaluation
Authors: Parrish Michael H , Dutcher Janine M , Muscatell Keely A , Inagaki Tristen K , Moieni Mona , Irwin Michael R , Eisenberger Naomi I
Published: January 2022

Self-enhancement, the tendency to view oneself positively, is a pervasive social motive widely investigated in the psychological sciences. Relatively little is known about the neurocognitive mechanisms underlying this motive, specifically in social-evaluative situations. To investigate whether positive emotion regulation circuitry, circuitry involved in modulating positive affect, relates to the self-enhancement motive in social contexts, we conducted an functional magnetic resonance imaging (fMRI) study in a healthy young adult sample. We hypothesized that self-enhancement indices (state and trait self-esteem) would relate to greater functional connectivity between right ventrolateral prefrontal cortex (RVLPFC), a region implicated in emotion regulation, and the ventral striatum (VS), a region associated with reward-related affect, during a social feedback task. Following social evaluation, participants experienced stable or decreased state self-esteem. Results showed that stable state self-esteem from pre- to post-scan and higher trait self-esteem related to greater RVLPFC–VS connectivity during positive evaluation. Stable-state self-esteem also related to greater RVLPFC–VS connectivity during negative evaluation. Moreover, RVLPFC activation during all types of feedback processing and left VS activation during negative feedback processing was greater for participants with stable-state self-esteem. These findings implicate neurocognitive mechanisms underlying emotion regulation in the self-enhancement motive and highlight a pathway through which self-enhancement may restore feelings of self-worth during threatening situations.
Development and Characterization of Novel Wheat-Rye 1RS·1BL Translocation Lines with High Resistance to Puccinia striiformis f. sp. tritici
Authors: Ren Tianheng , Jiang Qing , Sun Zixin , Ren Zhenglong , Tan Feiquan , Yang Wenyi , Li Zhi
Published: January 2022

Wheat-rye 1RS·1BL translocations from ‘Petkus’ rye have contributed substantially to wheat production worldwide with their great disease resistance and yield traits. However, the resistance genes on the 1RS chromosomes have completely lost their resistance to newly emerged pathogens. Rye could widen the variation of 1RS as a naturally cross-pollinated related species of wheat. In this study, we developed three new 1RS·1BL translocation lines by crossing rye inbred line BL1, selected from Chinese landrace rye Baili, with wheat cultivar Mianyang11. These three new translocation lines exhibited high resistance to the most virulent and frequently occurring stripe rust pathotypes and showed high resistance in the field, where stripe rust outbreaks have been most severe in China. One new gene for stripe rust resistance, located on 1RS of the new translocation lines, is tentatively named YrRt1054. YrRt1054 confers resistance to Puccinia striiformis f. sp. tritici pathotypes that are virulent toward Yr9 and YrCn17. This new resistance gene, YrRt1054, is available for wheat improvement programs. The present study indicated that rye cultivars may carry additional untapped variation as potential sources of resistance.
Integrating Oncology Education Into an Entry-Level Doctor of Physical Therapy Program Using a Systematic and Comprehensive Approach
Authors: Johnson Michael , Fu Wing , Brough Colleen , Yoon Lisa
Published: January 2022

In the United States, approximately 1.9 million cancer cases will be diagnosed in 2021. The 5-year relative survival rate for all cancers increased to 67%, with an estimated 16.9 million cancer survivors as of January 2019. Physical therapists have been advocated as an integral part of the oncology team throughout the cancer survivor trajectory; therefore, student physical therapists must be prepared to provide optimal care to the ever-increasing number of oncology patients and survivors through all phases of care—prediagnosis, diagnosis, treatment, and survival. The entry-level DPT Program at Columbia University (CUDPT) offers oncology education using a unique approach. The associated curriculum and co-curriculum thread through the entire program covers all levels of Miller's pyramid and follows both the constructivist theory and the experiential learning model. This is a presentation of the CUDPT entry-level curriculum for required courses as well as specific elective opportunities that expose students to oncology. Descriptions of specific courses and electives are provided to illustrate unique design and implementation of the oncology education in CUDPT. The illustration will cover the systematic and comprehensiveness of the education, along with the diversity and customizability of the educational activities. Ideas to strengthen the curriculum are presented as well as suggestions to develop or enhance oncology education opportunities at other entry-level programs. Examples of collaboration strategies with other stakeholders within the oncology community are provided.
An Online Elective Entry-Level Physical Therapy Oncology Course Guided by Qualitative Analysis of the Student Perspective
Authors: Croarkin Earllaine , Costello Ellen
Published: January 2022

Background:

As prevalence of cancer survivors continues to grow, physical therapists will play a major role in cancer rehabilitation. To meet growing educational needs for oncology physical therapy, the George Washington University DPT program developed an online elective course. Objectives: The purpose of this study was to explore student motivation for course enrollment, student self-perceived strengths and weaknesses in oncology physical therapy, and personal learning objectives.

Design:

Retrospective qualitative analysis.

Methods:

Pre and postcourse student narrative responses, based on self-reflection, were analyzed using a general inductive approach to identify themes.

Results:

Sixteen students enrolled in the course over 2 years. Students were interested in complex patient management and understood the effect of changing survival rates in future practice. Self-perceived strengths related to oncology physical therapy were rooted in communication skills, adaptability, compassion, and empathy. Students' perceived weaknesses and objectives ranged from oncological disease and treatment to safe physical therapy interventions. Students expressed concerns related to the emotional toll working with this population; they identified areas for future self-study.

Conclusion:

This course provided additional learning experiences in the management of patients with a cancer history. As adult learners, students identified learning objectives and explored topics in a supportive, self-directed learning environment. Educational needs related to oncological medical management and provision of safe and effective physical therapy interventions and psychosocial concerns expressed by our student group are similar to those of practicing clinicians. Qualitative analysis served as a useful tool to identify future course direction.
Differential Effects of Gamma-Aminobutyric Acidergic Sedatives on Risk of Post-Extubation Delirium in the ICU: A Retrospective Cohort Study From a New England Health Care Network
Authors: Azimaraghi Omid , Wongtangman Karuna , Wachtendorf Luca J. , Santer Peter , Rumyantsev Sandra , Ahn Curie , Kiyatkin Michael E. , Teja Bijan , Sarge Todd , Subramaniam Balachundhar , Eikermann Matthias
Published: January 2022

OBJECTIVES:

To evaluate whether different gamma-aminobutyric acidergic (GABAergic) sedatives such as propofol and benzodiazepines carry differential risks of post-extubation delirium in the ICU.

DESIGN:

Retrospective cohort study.

SETTING:

Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA).

PATIENTS:

Ten thousand five hundred and one adult patients mechanically ventilated for over 24 hours.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We tested the hypothesis that benzodiazepine versus propofol-based sedation is associated with fewer delirium-free days within 14 days after extubation. Further, we hypothesized that the measured sedation level evoked by GABAergic drugs is a better predictor of delirium than the drug dose administered. The proportion of GABAergic drug-induced deep sedation was defined as the ratio of days with a mean Richmond Agitation-Sedation Scale of less than or equal to –3 during mechanical ventilation. Multivariable regression and effect modification analyses were used. Delirium-free days were lower in patients who received a high proportion of deep sedation using benzodiazepine compared with propofol-based sedation (adjusted absolute difference, –1.17 d; 95% CI, –0.64 to –1.69; p < 0.001). This differential effect was magnified in elderly patients (age > 65) and in patients with liver or kidney failure (p-for-interaction < 0.001) but not observed in patients who received a low proportion of deep sedation (p = 0.95). GABAergic-induced deep sedation days during mechanical ventilation was a better predictor of post-extubation delirium than the GABAergic daily average effective dose (area under the curve 0.76 vs 0.69; p < 0.001).

CONCLUSIONS:

Deep sedation during mechanical ventilation with benzodiazepines compared with propofol is associated with increased risk of post-extubation delirium. Our data do not support the view that benzodiazepine-based compared with propofol-based sedation in the ICU is an independent risk factor of delirium, as long as deep sedation can be avoided in these patients.
Consequences of hyperandrogenemia during pregnancy in female offspring: attenuated response to angiotensin II
Authors: Shawky Noha M. , Dalmasso Carolina , Ojeda Norma B. , Zuchowski Yvonne , Stachenfeld Nina , Alexander Barbara T. , Reckelhoff Jane F.
Published: January 2022

Background:

Polycystic ovary syndrome (PCOS) is characterized by reproductive and metabolic dysfunction, and elevated blood pressure (BP). The cardiometabolic consequences of maternal hyperandrogenemia on offspring, either as adults or with aging, have not been well studied. We previously found that male offspring of hyperandrogenemic female (HAF) rats, a model of PCOS, are normotensive but have an exaggerated pressor response to angiotensin (Ang) II.

Method:

In this study, the hypothesis was tested that adult and aging female offspring of HAF rats develop a metabolic and hypertensive phenotype. Control and HAF rats were implanted prepubertally with placebo or dihydrotestosterone pellets, which continued throughout pregnancy and lactation.

Results:

Female offspring of HAF dams had lower birth weight than female control offspring. Although female HAF offspring (aged 16–24 weeks) had no differences in intrarenal Ang II, plasma lipids or proteinuria, they did have lower intrarenal Ang (1–7) and lower nitrate/nitrite excretion than controls. Adult HAF offspring had similar baseline BP as controls, but had an attenuated pressor response to Ang II. With aging (16–20 months), female HAF offspring remained normotensive with an attenuated pressor response to Ang II and high salt diet but more proteinuria and higher intrarenal Ang(1–7) than controls.

Conclusion:

Taken together, these data suggest that female HAF offspring are protected from developing hypertension, but may be at risk for renal injury with aging. Future studies are necessary to determine whether adult and postmenopausal offspring of PCOS women are at increased risk for cardiovascular dysfunction.

Graphical abstract:
http://links.lww.com/HJH/B820
Potential to Decrease Hospital Readmission Reduction Program Penalty Through Pharmacist Discharge Visits
Authors: Zupec Jason , Smith Jennifer N. , Fernandez Natalie , Otsuka Shelley , Lucado F. Greg
Published: January 2022

Goal:

We explored how investment in pharmacist services may be beneficial for health systems at risk for Hospital Readmission Reductions Program reimbursement penalties from the Centers for Medicare & Medicaid Services. Our aim was to determine to what extent reduction in readmission penalties justifies the increased operational cost of integrating a pharmacist in the delivery of transitions of care services in the outpatient setting.

Methods:

We created a mathematical model using incremental costs to evaluate the potential benefit from penalty reduction over a range of patient discharge volumes and excess readmission ratios (ERRs). The model estimates were based on the following assumptions: a national average of 13.45% of all Medicare discharges being measured by the program, an average of 40 minutes of pharmacist time per Medicare patient discharge, and a pharmacist hourly total payroll cost of $91.00 per hour.

Principal Findings:

Institutions in our model with discharge volumes ranging from 1,000 to 7,000 patients annually and an ERR of 1.1–1.3 benefited from pharmacist posthospital discharge visits, achieving a 15% reduction in early readmissions. Estimated annual net savings ranged from nearly $70,000 to just under $1,000,000. Net savings were greater for institutions with larger discharge volumes and higher initial ERRs.

Applications to Practice:

Healthcare managers overseeing transitions of care services need evidence-based strategies for reducing early readmission penalties. Our model shows that the additional cost of pharmacists providing outpatient transitions of care services could improve patient care and reduce early hospital readmission penalties. Institutions could target interventions to patients at high risk of readmission and further increase savings by limiting implementation costs.
New insights into the role of bempedoic acid and ezetimibe in the treatment of hypercholesterolemia
Authors: Pirillo Angela , Catapano Alberico L.
Published: January 2022

Purpose of review

A number of new cholesterol-lowering drugs have been recently developed and approved, enriching the pharmacological armamentarium beyond and above statins. Ezetimibe, available since two decades, and bempedoic acid, a new drug inhibiting the same biosynthetic pathway targeted by statins but at an early step, represent valuable tools for the treatment of hypercholesterolemia, particularly in specific groups of patients.

Recent findings

Bempedoic acid, either alone or in combination with ezetimibe, appears to reduce significantly LDL-C levels, an effect that has been observed also in patients with statin intolerance. A Mendelian randomization study has anticipated a protective cardiovascular effect of bempedoic acid; a randomized clinical trial is currently assessing whether the pharmacological control of hypercholesterolemia with bempedoic acid translates into a clinical benefit. Bempedoic acid, as well as ezetimibe, does not appear to induce adverse events in muscles; moreover, whereas statins are associated with a modest, although significant, increased risk of new-onset diabetes, bempedoic acid does not, at least based on the available evidence.

On the basis of available data, and while awaiting the results of the outcome trial, bempedoic acid appears to represent a valuable approach for the treatment of hypercholesterolemia, either alone or in combination in ezetimibe.
Clinicopathologic and Genetic Features of Primary T-cell Lymphomas of the Central Nervous System
Authors: Yim Jeemin , Koh Jiwon , Kim Sehui , Song Seung Geun , Bae Jeong Mo , Yun Hongseok , Sung Ji-Youn , Kim Tae Min , Park Sung-Hye , Jeon Yoon Kyung
Published: January 2022

Primary central nervous system lymphoma (PCNSL) of peripheral T-cell lineage (T-PCNSL) is rare, and its genetic and clinicopathologic features remain unclear. Here, we present 11 cases of T-PCNSL in immunocompetent individuals from a single institute, focusing on their genetic alterations. Seven cases were subject to targeted panel sequencing covering 120 lymphoma-related genes. Nine of the eleven cases were classified as peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), of which one was of γδT-cell lineage. There was one case of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma and another of extranodal natural killer (NK)/T-cell lymphoma (ENKTL) of αβT-cell lineage. The male to female ratio was 7 : 4 and the age ranged from 3 to 75 years (median, 61 y). Most patients presented with neurological deficits (n=10) and showed multifocal lesions (n=9) and deep brain structure involvement (n=9). Tumor cells were mostly small-to-medium, and T-cell monoclonality was detected in all nine evaluated cases. PTCL-NOS was CD4-positive (n=4), CD8-positive (n=3), mixed CD4-positive and CD8-positive (n=1), or CD4/CD8-double-negative (n=1, γδT-cell type). Cytotoxic molecule expression was observed in 4 (67%) of the 6 evaluated cases. Pathogenic alterations were found in 4 patients: one PTCL-NOS case had a frameshift mutation in KMT2C, another PTCL-NOS case harbored a truncating mutation in TET2, and another (γδT-cell-PTCL-NOS) harbored NRAS G12S and JAK3 M511I mutations, and homozygous deletions of CDKN2A and CDKN2B. The ENKTL (αβT-cell lineage) case harbored mutations in genes ARID1B, FAS, TP53, BCOR, KMT2C, POT1, and PRDM1. In conclusion, most of the T-PCNSL were PTCL-NOS, but sporadic cases of other subtypes including γδT-cell lymphoma, anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, and ENKTL were also encountered. Immunophenotypic analysis, clonality test, and targeted gene sequencing along with clinicoradiologic evaluation, may be helpful for establishing the diagnosis of T-PCNSL. Moreover, this study demonstrates genetic alterations with potential diagnostic and therapeutic utility in T-PCNSL.
Opioid Weaning Protocol Using Morphine Compared With Nonprotocolized Methadone Associated With Decreased Dose and Duration of Opioid After Norwood Procedure
Authors: Achuff Barbara-Jo , Lemming Katherine , Causey Jamie C. , Sembera Kerry A. , Checchia Paul A. , Heinle Jeffrey S. , Ghanayem Nancy S.
Published: January 2022

OBJECTIVES:

Opioids are used to manage pain, comfort, maintain devices, and decrease oxygen consumption around Norwood palliation (NP), but in high dose and prolonged exposure, they increase risk of tolerance and iatrogenic withdrawal syndrome (IAWS). Variability in practice for IAWS prevention potentially increases opioid dose and duration. We hypothesize that protocolized weaning with morphine (MOR) versus nonprotocolized methadone (MTD) is associated with reduction in opioid exposure.

DESIGN:

A before-versus-after study of outcomes of patients weaned with protocolized MOR versus nonprotocolized MTD including subset analysis for those patients with complications postoperatively. Primary endpoints include daily, wean phase, and total morphine milligram equivalent (MMEq) dose, duration, and, secondarily, length of stay (LOS).

SETTING:

Quaternary-care pediatric cardiac ICU.

PATIENTS:

Neonates undergoing single-ventricle palliation.

INTERVENTIONS:

Introduction of IAWS prevention protocol.

MEASUREMENTS AND MAIN RESULTS:

Analysis included 54 patients who underwent the NP in 2017–2018 including the subset analysis of 34 who had a complicated postoperative course. The total and wean phase opioid doses for the MTD group were significantly higher than that for the MOR group: 258 versus 22 and 115 versus 6 MMEq/kg; p < 0.001. Duration of opioid exposure was 63 days in the MTD group and 12 days in MOR group (p < 0.001). Subanalysis of the complicated subset also identifies higher total and wean dose for MTD group (293 vs 41 and 116 vs 7 MMEq/kg; p < 0.001) with a longer duration (65 vs 22 days; p = 0.001). Within the subset, LOS was 55% longer in the MTD group than that in the MOR group (150 vs 67 d; p = 0.01) and not different in the uncomplicated group.

CONCLUSIONS:

After complex NP, a protocolized opioid weaning using MOR versus MTD is associated with 65% shorter opioid duration, 10-fold decreased dose, and shortened LOS.
Longitudinal Assessment of Acute Concussion Outcomes Through SMS Text (ConText Study)
Authors: Schoenfeld Robert , Drendel Amy , Ahamed Sheikh Iqbal , Thomas Danny
Published: January 2022

Objective

Mild traumatic brain injury (mTBI), or concussion, is a common health problem that has seen a recent increase in US adolescents. This study uses SMS text messaging (a mobile health [mHealth] tool) to report patient symptoms. We aim to better characterize mTBI recovery and hypothesize that this mHealth tool will have high retention rates and correlate with a conventional means of assessing symptoms, the Post-Concussion Symptom Inventory (PCSI).

Methods

A prospective observational cohort pilot study. Thirty-one pediatric patients with acute mTBI were recruited to characterize their injury and report their symptoms via text messaging. Patients reported symptoms once every 3 days for the first 21 days, then once a week for 6 weeks.

Results

There was a strong and positive correlation between the PCSI and the mHealth tool (rs = 0.875,P< 0.000, n = 22). Retention was 74% until symptom resolution and 42% until study completion. Patients with balance deficits had a significantly higher somatization score than those with normal balance (6.53 ± 3.25 vs 2.56 ± 2.30,t(22) = 3.211,P< 0.01).

Conclusions

This pilot study demonstrates that this tool is a valid and easy-to-use method of reporting pediatric mTBI symptoms—it replicates and identifies novel findings. Our results suggest that there may be a relationship between balance and the manifestation of somatic symptoms. Retention rates were lower than predicted, indicating that text messaging may not be the ideal format in this population. Text messaging may still have other applications for short-term communication/symptom measurement.
Evaluation of Related Factors of Maxillary Sinusitis After Le Fort I Osteotomy Based on Computed Tomography: A Retrospective Case-Control Study
Authors: Wang Shoupeng , Qian Yifeng , Qi Lei , Ge Weiwen , Cao Ningning , Zhang Lei , Meng Jian
Published: January 2022

Maxillary sinusitis is 1 of the postoperative complications of the Le Fort I osteotomy, this study investigated the related factors of maxillary sinusitis after Le Fort I osteotomy. A total of 23 cases, 92 controls, and 11 related factors were included in this case-control study with a 1:4 case-control ratio. The risk factors for maxillary sinusitis after Le Fort I were examined by least absolute shrinkage and selection operator multivariate conditional logistic regression and least absolute shrinkage and selection operator multivariate linear regression. The patency of maxillary sinus ostium at 6 months after surgery was significantly associated with maxillary sinusitis after Le Fort I osteotomy. Compared with the obstructed maxillary sinus ostium, the percentage of the volume of the healthy air cavity in the complete sinus cavity increased 70.7% when the maxillary sinus ostium was unobstructed, and 95% confidence interval was 0.610 to 0.805. Similarly, when the maxillary sinus ostium was wide, the percentage increased 6.0% compared with the narrow 1, and 95% confidence interval was 0.013 to 0.107. This study indicated that the patency of maxillary sinus ostium has an important impact on maxillary sinusitis after Le Fort I osteotomy. Close attention should be paid to maintain the maxillary sinus ostium and the drainage of maxillary sinuses unobstructed in a clinical setting.
International Human Xenotransplantation Inventory: A 10-year Follow-up
Authors: Hu Xiaowei , Geng Zhen , Gonelle-Gispert Carmen , Hawthrone Wayne J. , Deng Shaoping , Buhler Leo
Published: January 2022

Background.

Following the recommendations by a panel of experts gathered by the World Health Organization in 2005, an inventory was established to collect practices of human xenotransplantation worldwide (www.humanxenotransplant.org). The website was activated in October 2006, in collaboration with the International Xenotransplantation Association, the University Hospital Geneva, and the World Health Organization. A first report on the collected xenotransplantation activities was published in 2010 in the journal Transplantation. In 2020, the website was redesigned, and its hosting and management were transferred to the Sichuan Provincial People’s Hospital.

Methods.

We collected information from publications in scientific journals, presentations at international congresses, the internet, and declarations of International Xenotransplantation Association members on xenotransplantation procedures in humans performed over the past 10 y.

Results.

A total of 5 new applications of human xenotransplantation were identified, with pig as source animal in all applications. The procedures involved transplantation of islets of Langerhans, skin, cornea, and choroid plexus cells. The treatments were performed in China, United States, New Zealand, and Argentina. No major complications or deaths were reported.

Conclusions.

Several clinical applications of cell or tissue xenotransplantation are ongoing around the world. Compared with the previous reported period (1995–2010, with 29 activities, mostly without governmental regulation), the recent number of clinical activities was reduced, and all were officially approved. This information should be used to inform healthcare officials, staff, and the public with the objective of encouraging good practices based on internationally harmonized guidelines driven by initiatives such as the Changsha Communiqué.
Barriers to the use of methylphenidate in paediatric neuro-oncology services
Authors: Hagan Alexander J. , Bailey Simon , Verity Sarah J.
Published: January 2022

Background

The increasing effectiveness of childhood cancer treatment has resulted in a greater number of children surviving previously incurable central nervous system tumours. This growing population of survivors report significant treatment-related difficulties, including attentional impairment associated with poor long-term intellectual development, academic attainment, and health-related quality of life. Clinical findings show benefit to attention and executive functions following methylphenidate administration. The current project explored barriers associated with use of methylphenidate in paediatric neuro-oncology services in the UK.

Method

Qualitative data was gathered by semi-structured questionnaire sent to clinical psychologists/neuropsychologists in 19 of the 21 NHS primary treatment oncology centres in the UK in May 2018. Thematic analytic methods were used to explore the data.

Results

11 responses were received from primary treatment centres. Knowledge of the evidence base for methylphenidate in paediatric brain injury was limited. This was primarily attributable to the inadequate resource of psychology into many primary treatment centres, limiting provision to service to a restricted proportion of the patient group. Psychologists reported an interest in exploring the utility of methylphenidate in their patient group. Respondents highlighted the need for provision of accessible research summaries and treatment protocols addressing the potential use of psychostimulants, stating that these would support their team to consider expanding the interventions offered.

Conclusions

The development of shared resources for clinicians will be important in supporting the application of research findings to clinical practice. We anticipate national collaboration will support the advancement of intervention for the growing clinical population of long-term survivors.
The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein
Authors: Peacock Thomas P. , Brown Jonathan C. , Zhou Jie , Thakur Nazia , Sukhova Ksenia , Newman Joseph , Kugathasan Ruthiran , Yan Ada W.C. , Furnon Wilhelm , De Lorenzo Giuditta , Cowton Vanessa M. , Reuss Dorothee , Moshe Maya , Quantrill Jessica L. , Platt Olivia K. , Kaforou Myrsini , Patel Arvind H. , Palmarini Massimo , Bailey Dalan , Barclay Wendy S.
Published: January 2022

The SARS-CoV-2 Omicron/BA.1 lineage emerged in late 2021 and rapidly displaced the Delta variant before being overtaken itself globally by, the Omicron/BA.2 lineage in early 2022. Here, we describe how Omicron BA.1 and BA.2 show a lower severity phenotype in a hamster model of pathogenicity which maps specifically to the spike gene. We further show that Omicron is attenuated in a lung cell line but replicates more rapidly, albeit to lower peak titres, in human primary nasal cells. This replication phenotype also maps to the spike gene. Omicron spike (including the emerging Omicron lineage BA.4) shows attenuated fusogenicity and a preference for cell entry via the endosomal route. We map the altered Omicron spike entry route and partially map the lower fusogenicity to the S2 domain, particularly the substitution N969K. Finally, we show that pseudovirus with Omicron spike, engineered in the S2 domain to confer a more Delta-like cell entry route retains the antigenic properties of Omicron. This shows a distinct separation between the genetic determinants of these two key Omicron phenotypes, raising the concerning possibility that future variants with large antigenic distance from currently circulating and vaccine strains will not necessarily display the lower intrinsic severity seen during Omicron infection.
In vitro evaluation of therapeutic antibodies against a SARS-CoV-2 Omicron B.1.1.529 isolate
Authors: Touret Franck , Baronti Cécile , Bouzidi Hawa Sophia , de Lamballerie Xavier
Published: January 2022

The emergence and rapid spread of the Omicron variant of SARS-CoV-2, which has more than 30 substitutions in the spike glycoprotein, compromises the efficacy of currently available vaccines and therapeutic antibodies. Using a clinical strain of the Omicron variant, we analyzed the neutralizing power of eight currently used monoclonal antibodies compared to the ancestral B.1 BavPat1 D614G strain. We observed that six of these antibodies have lost their ability to neutralize the Omicron variant. Of the antibodies still having neutralizing activity, Sotrovimab/Vir-7831 shows the smallest reduction in activity, with a factor change of 3.1. Cilgavimab/AZD1061 alone shows a reduction in efficacy of 15.8, resulting in a significant loss of activity for the Evusheld cocktail (42.6 fold reduction) in which the other antibody, Tixagevimab, does not retain significant activity against Omicron. Our results suggest that the clinical efficacy of the initially proposed doses should be rapidly evaluated and the possible need to modify doses or propose combination therapies should be considered.
A dual-receptor mechanism between integrins and ACE2 widens SARS-CoV-2 tissue tropism
Authors: Nader Danielle , Gressett Timothy E. , Hossen Md Lokman , Chapagain Prem , Kerrigan Steven W. , Bix Gregory
Published: January 2022

In addition to the ACE2 receptor, SARS-CoV-2 binds to integrins to gain host cell entry and trigger pro-inflammatory integrin-mediated signalling cascades. Integrins, therefore, are likely candidates for a dual-receptor mechanism with ACE2 to explain the increased infectivity seen in SARS-CoV-2 models. As integrins are primarily expressed in vasculature and persistent vasculopathy is seen in COVID-19, examining the role of endothelial integrin involvement is crucial in uncovering the pathophysiology of SARS-CoV-2.
Reduced Pathogenicity of the SARS-CoV-2 Omicron Variant in Hamsters
Authors: McMahan Katherine , Giffin Victoria , Tostanoski Lisa H. , Chung Benjamin , Siamatu Mazuba , Suthar Mehul S. , Halfmann Peter , Kawaoka Yoshihiro , Piedra-Mora Cesar , Martinot Amanda J. , Kar Swagata , Andersen Hanne , Lewis Mark G. , Barouch Dan H.
Published: January 2022

The SARS-CoV-2 Omicron (B.1.1.529) variant has proven highly transmissible and has outcompeted the Delta variant in many regions of the world1. Early reports have also suggested that Omicron may result in less severe clinical disease in humans. Here we show that Omicron is less pathogenic than prior SARS-CoV-2 variants in Syrian golden hamsters. Infection of hamsters with the SARS-CoV-2 WA1/2020, Alpha, Beta, or Delta strains led to 4-10% weight loss by day 4 and 10-17% weight loss by day 6, as expected2,3. In contrast, infection of hamsters with two different Omicron challenge stocks did not result in any detectable weight loss, even at high challenge doses. Omicron infection still led to substantial viral replication in both the upper and lower respiratory tracts and pulmonary pathology, but with a trend towards higher viral loads in nasal turbinates and lower viral loads in lung parenchyma compared with WA1/2020 infection. These data suggest that the SARS-CoV-2 Omicron variant may result in more robust upper respiratory tract infection but less severe lower respiratory tract clinical disease compared with prior SARS-CoV-2 variants.
Druggable redox pathways against M. abscessus in cystic fibrosis patient-derived airway organoids
Authors: Leon-Icaza Stephen Adonai , Bagayoko Salimata , Vergé Romain , Iakobachvili Nino , Ferrand Chloé , Aydogan Talip , Bernard Celia , Dafun Angelique Sanchez , Murris-Espin Marlène , Mazières Julien , Bordignon Pierre Jean , Mazères Serge , Bernes-Lasserre Pascale , Ramé Victoria , Lagarde Jean-Michel , Marcoux Julien , Bousquet Marie Pierre , Chalut Christian , Guilhot Christophe , Clevers Hans , Peters Peter J. , Molle Virginie , Lugo-Villarino Geanncarlo , Cam Kaymeuang , Berry Laurence , Meunier Etienne , Cougoule Céline
Published: January 2022

Mycobacterium abscessus(Mabs) drives life-shortening mortality in cystic fibrosis (CF) patients, primarily because of its resistance to chemotherapeutic agents. To date, our knowledge on the host and bacterial determinants driving Mabs pathology in CF patient lung remains rudimentary. Here, we used human airway organoids (AOs) microinjected with smooth (S) or rough (R-)Mabs to evaluate bacteria fitness, host responses to infection, and new treatment efficacy. We show that S Mabs formed biofilm, R Mabs formed cord serpentines and displayed a higher virulence. While Mabs infection triggers enhanced oxidative stress, pharmacological activation of antioxidant pathways resulted in better control of Mabs growth. Genetic and pharmacological inhibition of the CFTR is associated with better growth and higher virulence of S and R Mabs. Finally, pharmacological activation of antioxidant pathways inhibited Mabs growth and improved efficacy in combination with cefoxitin, a first line antibiotic. In conclusion, we have established AOs as a suitable human system to decipher mechanisms of CF-driven respiratory infection by Mabs and propose antioxidants as a potential host-directed strategy to improve Mabs infection control.
Quality assessment of anatomical MRI images from Generative Adversarial Networks: human assessment and image quality metrics
Authors: Treder Matthias S. , Codrai Ryan , Tsvetanov Kamen A.
Published: January 2022

Background

Generative Adversarial Networks (GANs) can synthesize brain images from image or noise input. So far, the gold standard for assessing the quality of the generated images has been human expert ratings. However, due to limitations of human assessment in terms of cost, scalability, and the limited sensitivity of the human eye to more subtle statistical relationships, a more automated approach towards evaluating GANs is required.

New method

We investigated to what extent visual quality can be assessed using image quality metrics and we used group analysis and spatial independent components analysis to verify that the GAN reproduces multivariate statistical relationships found in real data. Reference human data was obtained by recruiting neuroimaging experts to assess real Magnetic Resonance (MR) images and images generated by a Wasserstein GAN. Image quality was manipulated by exporting images at different stages of GAN training.Results: Experts were sensitive to changes in image quality as evidenced by ratings and reaction times, and the generated images reproduced group effects (age, gender) and spatial correlations moderately well. We also surveyed a number of image quality metrics which consistently failed to fully reproduce human data. While the metrics Structural Similarity Index Measure (SSIM) and Naturalness Image Quality Evaluator (NIQE) showed good overall agreement with human assessment for lower-quality images (i.e. images from early stages of GAN training), only a Deep Quality Assessment (QA) model trained on human ratings was sensitive to the subtle differences between higher-quality images.

Conclusions

We recommend a combination of group analyses, spatial correlation analyses, and both distortion metrics (SSIM, NIQE) and perceptual models (Deep QA) for a comprehensive evaluation and comparison of brain images produced by GANs.
Demonstration of a common DPhe7 to DNal(2’)7 peptide ligand antagonist switch for the melanocortin-3 and melanocortin-4 receptors identifies systematic mischaracterization of the pharmacological properties of melanocortin peptides
Authors: Gimenez Luis E , Noblin Terry A. , Williams Savannah Y. , Bagchi Satarupa Mullick , Ji Ren-Lei , Tao Ya-Xiong , Jeppesen Claus B. , Conde-Frieboes Kilian W. , Sawyer Tomi K. , Grieco Paolo , Cone Roger D.
Published: January 2022

Melanocortin peptides containing a D-naphthylalanine residue in position 7 (DNal(2’)7), reported as melanocortin-3 receptor (MC3R) subtype-specific agonists in two separate publications, were found to lack significant MC3R agonist activity. The cell lines used at the University of Arizona for pharmacological characterization of these peptides, consisting of HEK293 cells stably transfected with human melanocortin receptor subtypes MC1R, MC3R, MC4R, or MC5R, were then obtained and characterized by quantitative PCR. While the MC1R cell line correctly expressed only the hMCR1, the three other cell lines were mischaracterized with regard to receptor subtype expression. Demonstration that a D-naphthylalanine residue in position 7, irrespective of the melanocortin peptide template, results primarily in antagonism of the MC3R and MC4R, then allowed us to search the published literature for additional errors. The erroneously characterized DNal(2’)7-containing peptides date back to 2003; thus, our analysis suggests that systematic mischaracterization of the pharmacological properties of melanocortin peptides occurred.
An integrated approach to protein discovery and detection from complex biofluids
Authors: Luu Gordon T. , Ge Chang , Tang Yisha , Li Kailiang , Cologna Stephanie M. , Burdette Joanna E. , Su Judith , Sanchez Laura M.
Published: January 2022

Ovarian cancer, a leading cause of cancer related deaths among women, has been notoriously difficult to routinely screen for and diagnose early. Researchers and clinicians continue to seek routinely usable, non-invasive, screening methods as early detection significantly improves survival. Biomarker screening is ideal; however, currently available ovarian cancer biomarkers lack desirable sensitivity and specificity. Furthermore, the most fatal forms, high grade serous cancers often originate in the fallopian tube; therefore, sampling from the vaginal environment provides more proximal sources for tumor detection. To address these shortcomings and leverage proximal sampling, we developed an untargeted mass spectrometry microprotein profiling method and identified a signature of cystatin A, validated this protein in an animal model, and sought to overcome the limits of detection inherent to mass spectrometry by demonstrating that cystatin A is present at 100 pM concentrations using a label-free microtoroid resonator. The findings highlight the potential utility for early-stage detection where cystatin A levels would be low.

Significance Statement

It is now clear that high-grade serous ovarian cancer can originate in the fallopian tube epithelium. These tumors colonize the ovary and then metastasize throughout the peritoneum. This discovery has raised important, and yet unaddressed, questions how we might be able to detect and screen for this deadly disease for which there is no routine screening. We have leveraged vaginal lavages from a murine model of the disease as a complex biological fluid for untargeted discovery of microproteins using mass. We improved our limits of detection by conjugating a cystatin A antibody to the surface of a microtoroid resonator to allow us to specifically detect cystatin A from vaginal lavages at early time points across biological replicates.
Calculation of centralities in protein kinase A
Authors: Kornev Alexandr P. , Aoto Phillip C. , Taylor Susan S.
Published: January 2022

Topological analysis of amino acid networks is a common method that can help to understand the roles of individual residues. The most popular approach for network construction is to create a connection between residues if they interact. These interactions are usually weighted by absolute values of correlation coefficients or mutual information. Here we argue that connections in such networks have to reflect levels of cohesion within the protein instead of a simple fact of interaction between residues. If this is correct, an indiscriminate combination of correlation and anti-correlation, as well as the all-inclusive nature of the mutual information metrics, should be detrimental for the analysis. To test our hypothesis, we studied amino acid networks of the protein kinase A created by Local Spatial Pattern alignment, a method that can detect conserved patterns formed by Cα-Cβ vectors. Our results showed that, in comparison with the traditional methods, this approach is more efficient in detecting functionally important residues. Out of four studied centrality metrics, Closeness centrality was the least efficient measure of residue importance. Eigenvector centrality proved to be ineffective as the spectral gap values of the networks were very low due to the bilobal structure of the kinase. We recommend using joint graphs of Betweenness centrality and Degree centrality to visualize different aspects of amino acid roles.

Author Summary

Protein structures can be viewed as networks of residues with some of them being a part of highly interconnected hubs and some being connectors between the hubs. Analysis of these networks can be helpful for understanding of possible roles of single amino acids. In this paper, we challenged existing methods for the creation of such networks. A traditional way is to connect residues if they can interact. We propose that residues should be connected only if they retain their mutual positions in space during molecular dynamic simulation, that is they move cohesively. We show that this approach improves the efficiency of the analysis indicating that a significant revision of the existing views on amino acid networks is necessary.
Trait variation between and within Andes and coastal mountain ranges in the iconic South American treeAraucaria araucanain Chile
Authors: McIntosh Mariah , González-Campos Jorge , Demaree Patrick , Toro-Salamanca Omayra , Ipinza Roberto , Bustamante-Sánchez Marcela A. , Hasbún Rodrigo , Nelson Cara R.
Published: January 2022

As global commitments to restoration are underway, science is needed to support capacity to achieve meaningful gains for ecosystems and human communities. In Chile, identification and generation of appropriate plant material is a barrier to achieving major restoration goals under the Paris Climate Agreement. Understanding genetic differentiation among plant populations is needed to maximize restoration success. ForAraucaria araucana, a highly threatened iconic South American tree, this information is greatly needed to guide restoration and conservation efforts because this species occurs across a strong climate gradient. We grew seedlings from 12 populations ofA. araucanaacross its range in Chile in a common garden to assess regional (coastal versus Andes mountain ranges) and population variation in key plant traits and relate this variation to environmental variables. We demonstrate thatA. araucanais differentiated within regions and populations across its range in Chile by a suite of traits, particularly branch number and length (showing plant architectural differences) and needle width (showing leaf investment differences). We show that this variation is at least partly explained by climate and soil variables, with the most variation explained by differences between regions in temperature annual range. Thus, we recommend that restoration efforts focus on conserving genetic variation among and within regions and their populations and preventing the translocations of genotypes between coastal and Andes populations.
The determination of induction motor losses in steel taking into account its saturation
Authors: Zagirnyak Mykhaylo , Ogar Vita , Chenchevoi Volodymyr , Yatsiuk Rostyslav
Published: January 2022

Purpose

This paper aims to work out a method for calculating losses in induction motor steel taking into account its saturation.

Design/methodology/approach

The theory of electric machines is applied during the analysis of induction motor equivalent circuits. The theory of Fourier series is used to determine the harmonic components of voltage, current and power. Instantaneous power theory and trigonometric transformations are used to solve algebraic and differential equations and their systems. The methods of approximation and interpolation are applied to obtain analytical expressions from the experimental data. Experimental research was carried out to verify the reliability of theoretical provisions and research results.

Findings

A method for assessing an induction machine steel as a function of the generalized electromotive force has been proposed. It allows taking into account higher harmonics of the current, which are caused by the presence of nonlinearity of an induction motor magnetic circuit.

Practical implications

The obtained results can be used in calculating the energy characteristics and operating modes of an induction motor, as well as in the construction of control systems.

Originality/value

A method for determining the losses in the stator steel of an induction motor, using a generalized electromotive force, has been proposed for the first time. It enables taking into account the currents flowing both in the stator circuit and in the rotor circuit.
A model for mobile curation services in academic libraries
Authors: Yi Yong Jeong , Hwang Barun , Kim Donghun
Published: January 2022

Purpose

To better respond to user needs for personalized information services in the context of academic libraries, this study aims at developing a prototype to provide mobile curation services by using the concept of content curation.

Design/methodology/approach

This study used a mobile application software development process, which consisted of five phases: user and organizational requirements, architecture design, navigation design, page design and implementation and usability testing. Usability testing was conducted with a total of 20 college students by online surveys at a university.

Findings

Meta-analysis identified key user needs: diversification of services, more personalized services, active communication with librarians, quality improvement of information and interface improvement. User and organizational requirements derived four main service modules – namely, Curation Services, Live Chat, My Page and My Log. Usability testing regarding ease of use, perceived usefulness and satisfaction indicated that participants were satisfied with the prototype.

Research limitations/implications

The study extends the discussion of quality academic library services by introducing the concept of content curation that uses the advantages of mobile technologies to overcome existing limitations in library services insufficient for meeting individual user needs.

Originality/value

Although many studies have discussed mobile library services, few studies have focused on developing a system for such services. The model developed in the study fills the research gap. Above all, the key modules specified by the prototype – Curation Services, Live Chat, My Page and My Log services – are expected to improve existing research and learning support services currently offered by academic libraries.