bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety, Tolerability, and Pharmacokinetics of the Novel Hepatitis B Virus Expression Inhibitor GST-HG131 in Healthy Chinese Subjects: a First-in-Human Single- and Multiple-Dose Escalation Trial
Authors: Li Xiaojiao , Liu Yusi , Yao Hanxin , Wang Meng , Gao Lei , Lou Jinfeng , Mao John , Wu Wenqiang , Zhou Yixin , Tang Yanan , Yan Wenhao , Hu Yanbin , Ding Charles , Chen Shuhui , Niu Junqi , Ding Yanhua
Published: April 2022

GST-HG131, a novel dihydroquinolizinone (DHQ) compound, has been shown to reduce circulating levels of HBsAg in animals. This first-in-human trial evaluated the safety, tolerability, and pharmacokinetic profile of GST-HG131 in healthy Chinese subjects.
tRNA
fMet
Inactivating Mycobacterium tuberculosis VapBC Toxin-Antitoxin Systems as Therapeutic Targets
Authors: Chauhan Unnati , Barth Valdir C. , Woychik Nancy A.
Published: April 2022

The
Mycobacterium tuberculosis
genome contains an abundance of toxin-antitoxin (TA) systems, 50 of which belong to the VapBC family. The activity of VapC toxins is controlled by dynamic association with their cognate antitoxins—the toxin is inactive when complexed with VapB antitoxin but active when freed.
Species Distribution and Antifungal Susceptibilities of
Aspergillus
Section
Fumigati
Isolates in Clinical Samples from the United States
Authors: Badali Hamid , Cañete-Gibas Connie , McCarthy Dora , Patterson Hoja , Sanders Carmita , David Marjorie P. , Mele James , Fan Hongxin , Wiederhold Nathan P.
Published: April 2022

Aspergillus
species are capable of causing both invasive disease and chronic infections in immunocompromised patients or those with preexisting lung conditions.
Aspergillus fumigatus
is the most commonly cultured species, and there is increasing concern regarding resistance to the azoles, which are the mainstays of antifungal therapy against aspergillosis. We evaluated the species distribution and susceptibility profiles of isolates within
Aspergillus
section
Fumigati
in the United States over a 52-month period.
Molecular Basis of Functional Effects of Phosphorylation of the C-Terminal Domain of the Rabies Virus P Protein
Authors: Zhan Jingyu , Watts Ericka , Brice Aaron M. , Metcalfe Riley D. , Rozario Ashley M. , Sethi Ashish , Yan Fei , Bell Toby D. M. , Griffin Michael D. W. , Moseley Gregory W. , Gooley Paul R.
Published: April 2022

Rabies virus P protein is a multifunctional protein with critical roles in replication and manipulation of host-cell processes, including subversion of immunity. This functional diversity involves interactions of several P protein isoforms with the cell nucleus and microtubules.
Human Norovirus Triggers Primary B Cell Immune ActivationIn Vitro
Authors: Mirabelli Carmen , Jones Melissa K. , Young Vivienne L. , Kolawole Abimbola O. , Owusu Irene , Shan Mengrou , Abuaita Basel , Turula Holly , Trevino Jose G. , Grigorova Irina , Lundy Steven K. , Lyssiotis Costas A. , Ward Vernon K. , Karst Stephanie M. , Wobus Christiane E.
Published: April 2022

Human norovirus (HNoV) is the most prevalent causative agent of gastroenteritis worldwide. Infection results in a self-limiting disease that can become chronic and severe in the immunocompromised, the elderly, and infants.
Mac1-Dependent Copper Sensing Promotes
Histoplasma
Adaptation to the Phagosome during Adaptive Immunity
Authors: Ray Stephanie C. , Rappleye Chad A.
Published: April 2022

Histoplasma capsulatum
is a fungal pathogen that survives and grows within host macrophages. For successful infection,
Histoplasma
must sense and adapt to a dynamic intracellular environment over the course of an infection.
Genetic and Transcriptomic Characteristics of RhlR-Dependent Quorum Sensing in Cystic Fibrosis Isolates of Pseudomonas aeruginosa
Authors: Asfahl Kyle L. , Smalley Nicole E. , Chang Alexandria P. , Dandekar Ajai A.
Published: April 2022

The bacterial pathogen
Pseudomonas aeruginosa
can cause chronic infections that are resistant to treatment in immunocompromised individuals. Over the course of these infections, the original infecting organism adapts to the host environment.
P. aeruginosa
uses a cell-cell signaling mechanism termed quorum sensing (QS) to regulate virulence factors and cooperative behaviors.
Antitumor Activities of tRNA-Derived Fragments and tRNA Halves from Non-pathogenic Escherichia coli Strains on Colorectal Cancer and Their Structure-Activity Relationship
Authors: Cao Kai-Yue , Pan Yu , Yan Tong-Meng , Tao Peng , Xiao Yi , Jiang Zhi-Hong
Published: April 2022

While the gut microbiota has been increasingly recognized to be of vital importance for human health and disease, the current literature shows that there is a lack of attention given to non-pathogenic
Escherichia coli
strains. Moreover, the biological activities of tRNA fragments (tRFs) derived from bacteria have rarely been investigated.
Short Linear Motifs (SLiMs) in “Core” RxLR Effectors of
Phytophthora parasitica
var.
nicotianae
: a Case of PpRxLR1 Effector
Authors: Chepsergon Jane , Nxumalo Celiwe Innocentia , Salasini Brenda S. C. , Kanzi Aquillah M. , Moleleki Lucy Novungayo
Published: April 2022

The continuous gain and loss of RxLR effectors makes the control of
Phytophthora
spp. difficult. Therefore, in this study, we endeavored to identify RxLR effectors that are highly conserved among species, also known as “core” RxLR effectors (CREs).
New Late Cretaceous paleomagnetic results from the Lhasa terrane and their implications for the suturing of India and Eurasia and the closure of the Neo-Tethys Ocean
Authors: Tong Yabo , Yang Zhenyu , Pei Junling , Li Jianfeng , Jin Shuchen , Hou Lifu , Sun Xinxin , Zhang Zijian
Published: April 2022

The forms of the margins of the Lhasa terrane and the Tethyan Himalaya prior to the collision of India and Eurasia as constrained by paleomagnetism are ambiguous due to the disordered Cretaceous paleomagnetic data from the central Lhasa terrane and the counterclockwise rotation of the Indian plate during the Cretaceous. This ambiguity has induced controversy over the processes of suturing of India and Eurasia and the closure of the Neo-Tethys Ocean. We obtained a set of high-quality Late Cretaceous paleomagnetic data from the central Lhasa terrane, which, integrated with reliable Cretaceous and Paleogene paleomagnetic data sets from the other parts of the Lhasa terrane and Tethyan Himalaya, confirmed that the southern margin of the Lhasa terrane and the northern margin of the Tethyan Himalaya were originally oriented ∼317° and ∼326°, respectively, prior to the collision of India and Eurasia. The margins of the Lhasa terrane and Tethyan Himalaya were almost consistent with the original straight fold axes of Cretaceous strata in the southern part of the Lhasa terrane, which were oriented 332.5° ± 8.5°, indicating that the subduction of the Neo-Tethys Ocean beneath Eurasia and the movement of the Tethyan Himalaya consistently maintained a stabilized direction of 62.5° ± 8.5° during the Late Cretaceous. The different kinematic characteristics of the Indian plate and Tethyan Himalaya and the overlap of the margins of the Tethyan Himalaya and Lhasa terrane during 59.0–56.0 Ma indicate that the Tethyan Himalaya was already rifted from the Indian plate prior to 62.5–59.2 Ma, and then it quasi-parallelly collided with the Lhasa terrane during 59.0– 56.0 Ma, quasi-synchronously closing the Neo-Tethys Ocean.
Looking upstream with clumped and triple oxygen isotopes of estuarine oyster shells in the early Eocene of California, USA
Authors: Kelson Julia R. , Petersen Sierra V. , Niemi Nathan A. , Passey Benjamin H. , Curley Allison N.
Published: April 2022

The δ18O of carbonate minerals that formed at Earth's surface is widely used to investigate paleoclimates and paleo-elevations. However, a multitude of hydrologic processes can affect δ18O values, including mixing, evaporation, distillation of parent waters, and carbonate growth temperatures. We combined traditional carbon and oxygen isotope analyses with clumped (Δ47) and triple oxygen isotopes (Δ′17O) analyses in oyster shells (Acutostrea idriaensis) of the Goler Formation in southern California (USA) to obtain insights into surface temperatures and δ18O values of meteoric waters during the early Eocene hothouse climate. The Δ47-derived temperatures ranged from 9 °C to 20 °C. We found a correlation between the δ18O of growth water (δ18Ogw) (calculated using Δ47 temperatures and δ18O of carbonate) and the δ13C values of shells. The Δ′17O values of shell growth waters (0.006‰–0.013‰ relative to Vienna standard mean ocean water–standard light Antarctic precipitation [VSMOW-SLAP]) calculated from Δ′17O of carbonate (−0.087‰ to −0.078‰ VSMOW-SLAP) were lower than typical meteoric waters. These isotopic compositions are consistent with oyster habitation in an estuary. We present a new triple oxygen isotope mixing model to estimate the δ18O value of freshwater supplying the estuary (δ18Ofw). The reconstructed δ18Ofw of −11.3‰ to −14.7‰ (VSMOW) is significantly lower than the δ18Ogw of −4.4‰ to −9.9‰ that would have been calculated using “only” Δ47 and δ18O values of carbonate. This δ18Ofw estimate supports paleogeographic reconstructions of a Paleogene river fed by high-elevation catchments of the paleo–southern Sierra Nevada. Our study highlights the potential for paired Δ47 and Δ′17O analyses to improve reconstructions of meteoric water δ18O, with implications for understanding ancient climates and elevations.
Supplemental Material: Late glacial–Holocene record of Southern Hemisphere westerly wind dynamics from the Falkland Islands, South Atlantic Ocean
Authors: Monteath Alistair , al. et
Published: April 2022

Tables S1–S8 (radiocarbon dates, X-ray fluorescence core-scanning values, particle size measurements, inductively coupled plasma–mass spectrometry analyses, and pollen and plant macrofossil analyses used in this study), methods, and Figures S1–S5. 
Strongyloides stercoralis hyperinfection syndrome: a known entity in an unknown provenance
Authors: Naidu Yogeeta V , Calderon Candelario Rafael A , Kett Daniel H
Published: April 2022

A 49-year-old man was admitted with altered mental status, high-grade fevers, tachycardia and leucocytosis. Cerebrospinal fluid (CSF) was purulent with a markedly elevated nucleated cell count with neutrophilic predominance, elevated protein and low glucose. CSF gram stain was negative. Patient received vancomycin, cefepime, ampicillin and acyclovir for presumed meningitis. He was intubated for protection of airway and underwent bronchoscopy. Microscopic examination of the bronchoalveolar lavage noted Strongyloides filariform larvae. Ivermectin was prescribed. Other laboratory tests showed a positive HIV test associated with a low CD4 count. Stool ova and parasite also revealed Strongyloides and repeat lumbar puncture identified larvae in the CSF. Albendazole was added for adjunctive therapy. However, the patient suffered a large intraparenchymal haemorrhage extending into the ventricles and he expired 36 days after admission.
Risk of adverse events after covid-19 in Danish children and adolescents and effectiveness of BNT162b2 in adolescents: cohort study
Authors: Kildegaard Helene , Lund Lars Christian , Højlund Mikkel , Stensballe Lone Graff , Pottegård Anton
Published: April 2022

Objectives

To assess the risk of acute and post-acute adverse events after SARS-CoV-2 infection in children and adolescents in Denmark and to evaluate the real world effectiveness of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) among adolescents.

Design

Cohort study.

Setting

Nationwide Danish healthcare registers.

Participants

All Danish people younger than 18 years who were either tested for SARS-CoV-2 using reverse transcriptase polymerase chain reaction (RT-PCR) or vaccinated with BNT162b2 to 1 October 2021.

Main outcome measures

Risk of hospital admissions (any hospital contact of ≥12 hours); intensive care unit (ICU) admissions; serious complications, including multisystem inflammatory syndrome in children (MIS-C), myocarditis, and neuroimmune disorders; and initiating drug treatment and health service use up to six months after being tested. Vaccine effectiveness in vaccine recipients compared with unvaccinated peers was evaluated as one minus the risk ratio at 20 days after the first dose and 60 days after the second dose.

Results

Of 991 682 children and adolescents tested for SARS-CoV-2 using RT-PCR in Denmark, 74 611 (7.5%) were positive. The risk of hospital admission with any variant for ≥12 hours was 0.49% (95% confidence interval 0.44% to 0.54%; 361/74 350), and 0.01% (0.01% to 0.03%; 10/73 187) of participants were admitted to an ICU within 30 days of testing positive. The risk of MIS-C within two months of SARS-CoV-2 infection was 0.05% (0.03% to 0.06%; 32/70 666), whereas no participants had myocarditis outside of MIS-C or encephalitis and fewer than five had Guillain-Barré syndrome. In the post-acute phase (1-6 months after infection), participants who tested positive for SARS-CoV-2 showed a 1.08-fold (95% confidence interval 1.06-fold to 1.10-fold) increase in rate of contacts with general practitioners compared with a reference cohort sampled among all children tested for SARS-CoV-2 during the study period. Overall, 278 649 adolescents received BNT162b2. Compared with unvaccinated adolescents, the estimated vaccine effectiveness among 229 799 adolescents vaccinated with one dose was 62% (95% confidence interval 59% to 65%) after 20 days, and among 175 176 vaccinated with two doses was 93% (92% to 94%) after 60 days during a period when delta was the dominant variant.

Conclusions

The absolute risks of adverse events after SARS-CoV-2 infection were generally low in Danish children and adolescents, although MIS-C occurred in 0.05% (32/70 666) of participants with RT-PCR confirmed SARS-CoV-2 infection. In adjusted analyses, rates of general practitioner visits were slightly increased in SARS-CoV-2 positive children and adolescents, which could indicate persisting symptoms. BNT162b2 appeared to be effective in reducing the risk of SARS-CoV-2 infection with the delta variant in adolescents.
Cohort profile: the South African HIV Cancer Match (SAM) Study, a national population-based cohort
Authors: Muchengeti Mazvita , Bartels Lina , Olago Victor , Dhokotera Tafadzwa , Chen Wenlong Carl , Spoerri Adrian , Rohner Eliane , Bütikofer Lukas , Ruffieux Yann , Singh Elvira , Egger Matthias , Bohlius Julia
Published: April 2022

Purpose

The South African HIV Cancer Match (SAM) Study is a national cohort of people living with HIV (PLWH). It was created using probabilistic record linkages of routine laboratory records of PLWH retrieved by National Health Laboratory Services (NHLS) and cancer data from the National Cancer Registry. The SAM Study aims to assess the spectrum and risk of cancer in PLWH in the context of the evolving South African HIV epidemic. The SAM Study’s overarching goal is to inform cancer prevention and control programmes in PLWH in the era of antiretroviral treatment in South Africa.

Participants

PLWH (both adults and children) who accessed HIV care in public sector facilities and had HIV diagnostic or monitoring laboratory tests from NHLS.

Findings to date

The SAM cohort currently includes 5 248 648 PLWH for the period 2004 to 2014; 69% of these are women. The median age at cohort entry was 33.0 years (IQR: 26.2–40.9). The overall cancer incidence in males and females was 235.9 (95% CI: 231.5 to 240.5) and 183.7 (181.2–186.2) per 100 000 person-years, respectively.

Using data from the SAM Study, we examined national cancer incidence in PLWH and the association of different cancers with immunodeficiency. Cancers with the highest incidence rates were Kaposi sarcoma, cervix, breast, non-Hodgkin's lymphoma and eye cancer.

Future plans

The SAM Study is a unique, evolving resource for research and surveillance of malignancies in PLWH. The SAM Study will be regularly updated. We plan to enrich the SAM Study through record linkages with other laboratory data within the NHLS (eg, tuberculosis, diabetes and lipid profile data), mortality data and socioeconomic data to facilitate comprehensive epidemiological research of comorbidities among PLWH.
Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study
Authors:   Global Health Research Group on Children’s Non-Communicable Diseases Collaborative
Published: April 2022

Objectives

Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.

Design

A multicentre, international, collaborative cohort study.

Setting

91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.

Participants

Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.

Main outcome measure

All-cause mortality at 30 days and 90 days.

Results

1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001).

Conclusions

The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally.
Neuromodulation through brain stimulation-assisted cognitive training in patients with post-COVID-19 cognitive impairment (Neuromod-COV): study protocol for a PROBE phase IIb trial
Authors: Thams Friederike , Antonenko Daria , Fleischmann Robert , Meinzer Marcus , Grittner Ulrike , Schmidt Sein , Brakemeier Eva-Lotta , Steinmetz Anke , Flöel Agnes
Published: April 2022

Introduction

A substantial number of patients diagnosed with COVID-19 experience long-term persistent symptoms. First evidence suggests that long-term symptoms develop largely independently of disease severity and include, among others, cognitive impairment. For these symptoms, there are currently no validated therapeutic approaches available. Cognitive training interventions are a promising approach to counteract cognitive impairment. Combining training with concurrent transcranial direct current stimulation (tDCS) may further increase and sustain behavioural training effects. Here, we aim to examine the effects of cognitive training alone or in combination with tDCS on cognitive performance, quality of life and mental health in patients with post-COVID-19 subjective or objective cognitive impairments.

Methods and analysis

This study protocol describes a prospective randomised open endpoint-blinded trial. Patients with post-COVID-19 cognitive impairment will either participate in a 3-week cognitive training or in a defined muscle relaxation training (open-label interventions). Irrespective of their primary intervention, half of the cognitive training group will additionally receive anodal tDCS, all other patients will receive sham tDCS (double-blinded, secondary intervention). The primary outcome will be improvement of working memory performance, operationalised by an n-back task, at the postintervention assessment. Secondary outcomes will include performance on trained and untrained tasks and measures of health-related quality of life at postassessment and follow-up assessments (1 month after the end of the trainings).

Ethics and dissemination

Ethical approval was granted by the Ethics Committee of the University Medicine Greifswald (number: BB 066/21). Results will be available through publications in peer-reviewed journals and presentations at national and international conferences.

Trial registration number

NCT04944147.
Applying the health capability profile to empirically study chronic hepatitis B in rural Senegal: a social justice mixed-methods study protocol
Authors: Coste Marion , Badji Mouhamed Ahmed , Diallo Aldiouma , Mora Marion , Boyer Sylvie , Prah Jennifer J
Published: April 2022

Introduction

Despite the early implementation of hepatitis B vaccination and the ongoing decentralisation of chronic hepatitis B (CHB) care, over 10% of the Senegalese adult population lives with CHB and liver cancer remains a main cause of death. Investigating factors associated with CHB infection, prevention of CHB-related morbidity, and prevention and treatment of mortality secondary to CHB calls for a holistic and multidimensional approach. This paper presents the adaptation of the health capability profile (HCP) to a specific epidemiological issue and empirical setting: it seeks to identify and analyse inter-related abilities and conditions (health capabilities) in relation to the CHB epidemic in the rural area of Niakhar, Senegal.

Methods and analysis

This ongoing study relies on a sequential social justice mixed-methods design. The HCP is comprehensively adapted to CHB in rural Senegal and guides the design and conduct of the study. Objective and subjective data are collected at the individual level following a mixed-methods explanatory core design. The quantitative module, embedded in the ANRS12356 AmBASS cross-sectional survey (exhaustive sampling), is used to select a purposeful sampling of participants invited for one-on-one qualitative interviews. Additional data are collected at the institutional and community level through health facility surveys and an ethnography (in-depth interviews) of local and national CHB stakeholders. Data analysis adopts a synergistic approach to produce a multilayered analysis of individual HCPs and crosscutting analysis of the 15 health capabilities. The data integration strategy relies on a mixed-methods convergent core design, and will use 0–100 health capability scores as well as flow diagrams to measure and characterise levels of development and interactions among health capabilities, respectively.

Ethics and dissemination

This study was approved by Senegalese and French authorities. Results dissemination through local workshops and scientific publications aim at fuelling effective policy change towards CHB-related health capability.
ON-ICE trial: Investigation of the combined effects of oxytocin and naltrexone on stress-induced and alcohol cue-induced craving in alcohol use disorder–Study protocol of a phase II randomised double-blind placebo-controlled parallel-group trial
Authors: Zimmermann Sina , Thomas Bettina C , Krisam Johannes , Limprecht Ronald , Klose Christina , Stenger Manuel , Pourbaix Madeleine , Ries Marcel , Vollstaedt-Klein Sabine , Koopmann Anne , Lenz Bernd , Kiefer Falk , Bach Patrick
Published: April 2022

Introduction

Although alcohol dependence (AD) is highly prevalent, only few medications are approved for its treatment. While currently approved medications, such as naltrexone (NTX), reduce craving and relapse risk to a certain extent, new approaches are needed to complement these pharmaca. One potential compound is oxytocin (OXY), which proved beneficial effects on alcohol craving and stress reactivity in preliminary clinical studies and synergism with NTX effects.

Methods and analysis

This clinical phase II trial is a monocentre two-armed, placebo (PLC)-controlled, 1:1 randomised, double-blind, parallel-group study. 62 participants with AD will be randomised to receive either intranasal OXY spray (24 IU) or PLC spray plus oral NTX (50 mg) for 2 days, and alcohol craving will be assessed using a validated combined stress-exposure and cue-exposure experiments and MRI. The primary outcome will be the intensity of alcohol craving, assessed using the Alcohol Urge Questionnaire (AUQ), 60 min after OXY/PLC application, directly after the stress and cue exposures. Secondary outcomes include subjective stress, negative affect, cortisol and OXY plasma levels, and neural response to alcohol and emotional cues and natural rewards. Follow-up drinking data were collected over 90 days. The primary efficacy analysis will test the difference between the verum and the PLC group in the distribution of AUQ craving scores. Appropriate statistical analysis will be used for the evaluation of the secondary outcomes.

Ethics and dissemination

This trial has been approved by the ethics committee of Heidelberg University and competent authority. All participants in the trial will provide written informed consent. The study will be conducted according to the principles of the Declaration of Helsinki and in accordance to the German Medicinal Products act. Results of this study will be disseminated in peer-reviewed scientific journals and deidentified data, and the statistical analysis plan will be made available via open-access online repositories.

Trial registration numbers

EudraCT 2021-003610-40 and NCT05093296.
Predicting outcome after cardiac resynchronisation therapy defibrillator implantation: the cardiac resynchronisation therapy defibrillator Futility score
Authors: Maille Baptiste , Bodin Alexandre , Bisson Arnaud , Herbert Julien , Pierre Bertrand , Clementy Nicolas , Klein Victor , Franceschi Frédéric , Deharo Jean-Claude , Fauchier Laurent
Published: April 2022

Background

Risk-benefit for cardiac resynchronisation therapy (CRT) defibrillator (CRT-D) over CRT pacemaker remains a matter of debate. We aimed to identify patients with a poor outcome within 1 year of CRT-D implantation, and to develop a CRT-D Futility score.

Methods

Based on an administrative hospital-discharge database, all consecutive patients treated with prophylactic CRT-D implantation in France (2010–2019) were included. A prediction model was derived and validated for 1-year all-cause death after CRT-D implantation (considered as futility) by using split-sample validation.

Results

Among 23 029 patients (mean age 68±10 years; 4873 (21.2%) women), 7016 deaths were recorded (yearly incidence rate 7.2%), of which 1604 (22.8%) occurred within 1 year of CRT-D implantation. In the derivation cohort (n=11 514), the final logistic regression model included—as main predictors of futility—older age, diabetes, mitral regurgitation, aortic stenosis, history of hospitalisation with heart failure, history of pulmonary oedema, atrial fibrillation, renal disease, liver disease, undernutrition and anaemia. Area under the curve for the CRT-D Futility score was 0.716 (95% CI: 0.698 to 0.734) in the derivation cohort and 0.692 (0.673 to 0.710) in the validation cohort. The Hosmer-Lemeshow test had a p-value of 0.57 suggesting accurate calibration. The CRT-D Futility score outperformed the Goldenberg and EAARN scores for identifying futility. Based on the CRT-D Futility score, 15.9% of these patients were categorised at high risk (predicted futility of 16.6%).

Conclusions

The CRT-D Futility score, established from a large nationwide cohort of patients treated with CRT-D, may be a relevant tool for optimising healthcare decision-making.
Body iron stores had no impact on coronary heart disease outcomes: a middle-aged male cohort from the general population with 21-year follow-up
Authors: Barywani Salim Bary , Östgärd Thunström Erik , Mandalenakis Zacharias , Hansson Per-Olof
Published: April 2022

Background

Body iron stores (BISs) have been proposed to be related to the development of cardiovascular diseases. However, results from epidemiological studies are conflicting. Knowledge on the long-term impact of BIS on cardiovascular outcomes in the general population is lacking.

Purpose

The aim of this study was to explore the relationship between BIS and coronary heart disease (CHD) including death due to CHD.

Methods

This investigation is part of ‘The Study of Men Born in 1943’, a longitudinal prospective study of men living in the city of Gothenburg, Sweden. This random population sample was examined in 1993 (all at 50 years of age at baseline). A medical examination was performed, and questionnaires were used to evaluate lifestyle factors. Biomarkers for iron stores (serum ferritin and serum transferrin receptor) was analysed from frozen blood samples in 2014. All hospital admissions were registered through national registers during the entire follow-up from 1993 to 2014. HRs were estimated by Cox proportional-hazard regression analyses.

Results

During the 21 years follow-up period, 120 participants (15.2%) developed CHD and 16 patients (2%) died due to CHD. The all-cause mortality was 15.2% (n=120) including 40 cardiovascular deaths (5.1%). In a multivariable Cox regression analysis, the daily smoking, hypertension and the increased resting heart rate was independent predictors of CHD, while no significant association was found between BIS and risk of CHD.

Conclusions

In a cohort of middle-aged men from the general population with well validated and prospectively collected data, we did not find any association between serum ferritin or serum transferrin receptor as markers of BIS and CHD events after 21 years of follow-up.

Trail registration number

NCT03138122.
Prognostic value of microvascular resistance and its association to fractional flow reserve: a DEFINE-FLOW substudy
Authors: Eftekhari Ashkan , Westra Jelmer , Stegehuis Valérie , Holm Niels Ramsing , van de Hoef Tim P , Kirkeeide Richard L , Piek Jan J , Lance Gould K , Johnson Nils P , Christiansen Evald Høj
Published: April 2022

Objective

This study aimed to evaluate the prognostic value of hyperemic microvascular resistance (HMR) and its relationship with hyperemic stenosis resistance (HSR) index and fractional flow reserve (FFR) in stable coronary artery disease.

Methods

This is a substudy of the DEFINE-FLOW cohort (NCT02328820), which evaluated the prognosis of lesions (n=456) after combined FFR and coronary flow reserve (CFR) assessment in a prospective, non-blinded, non-randomised, multicentre study in 12 centres in Europe and Japan. Participants (n=430) were evaluated by wire-based measurement of coronary pressure, flow and vascular resistance (ComboWire XT, Phillips Volcano, San Diego, California, USA).

Results

Mean FFR and CFR were 0.82±0.10 and 2.2±0.6, respectively. When divided according to FFR and CFR thresholds (above and below 0.80 and 2.0, respectively), HMR was highest in lesions with FFR>0.80 and CFR<2.0 (n=99) compared with lesions with FFR≤0.80 and CFR≥2.0 (n=68) (2.92±1.2 vs 1.91±0.64 mm Hg/cm/s, p<0.001). The FFR value was proportional to the ratio between HMR and the HMR+HSR (total resistance), 95% limits of agreement (−0.032; 0.019), bias (−0.003±0.02) and correlation (r2=0.98, p<0.0001). Cox regression model using HMR as continuous parameter for target vessel failure showed an HR of 1.51, 95% CI (0.9 to 2.4), p=0.10.

Conclusions

Increased HMR was not associated with a higher rate of adverse clinical events, in this population of mainly stable patients. FFR can be equally well expressed as HMR/HMR+HSR, thereby providing an alternative conceptual formulation linking epicardial severity with microvascular resistance.

Trial registration number

NCT02328820.
Delivering surgical education: a specialist surgical society and undergraduate student collaboration
Authors: Singh Shashwat , Thiagarajah Viswan , Banerjee Rishi , Iyenger Kartik , Garg Sunil , Singh Bijayendra , Ahluwalia Raju ,   BIOS Collaborative, Shah Nilesh , Koka Ravi , Sinha Amit , Khanduja Vikas , Kotwal Rahul , Anand Sanjeev , Gill Inder , Tolat Amat , Desai Aravind
Published: April 2022

Currently, the delivery of the undergraduate medical curriculum includes various teaching, learning and assessment strategies. Self-directed learning is an important aspect of this mix and includes the use of resources, sometimes not provided by the parent University, in the student’s own time to enhance the student’s knowledge, skills and professional practice. Societies aimed at a particular specialty contain a pool of professionals that can provide undergraduate students with opportunities for further self-directed learning, development of specialty-specific core skills and exploration of research interests. This may then enhance and enlighten the students’ approach to a particular orthopaedic problem and reinforce the curriculum they are studying while providing an understanding of current areas of debate that are not part of the curriculum at present. The collaboration of postgraduate societies with undergraduate students in developing and implementing undergraduate engagement strategies is of benefit to undergraduate education, the specialty society and the collaborating students. We explore the planning and implementation of an interactive webinar series run by the British Indian Orthopaedic Society in collaboration with undergraduate students. We provide a case study of a surgical specialty society engaging with undergraduate students with synergistic effect. We pay particular attention to the benefits accrued by the specialty society and the student collaborators by this joint effort.
“Sudbury Breccia” and “Huronian Breccia”: spatial, sedimentological, and structural evidence for separate distinct breccia-forming events
Authors: Morris W.A. , Ferris G. , Slavinski H.A.
Published: April 2022

Rounded argillite clasts within the lower Gowganda Formation of the Huronian Supergroup near Whitefish Falls, Ontario, have been historically mapped as Sudbury Breccia, implying that their formation was initiated by the Sudbury meteorite impact event. Alternative genetic models proposed to explain the breccia at Whitefish Falls include formation through intrusion of diabase into wet sediment accompanied by soft-sediment deformation events. Outcrops in the Whitefish Falls area contain clear evidence for early post-depositional fracturing: flow of argillites into brittle fractured sandstones. Linking these geological processes suggests that the formation of the breccia at Whitefish Falls was generated by faulting of the Huronian sedimentary basin during the sedimentation of the Gowganda argillites. Using a GIS approach to compare the distribution of known breccia bodies with mapped lithology and structure, it is apparent that the term Sudbury Breccia has been applied to two types of breccias. First, true Sudbury Breccia, which is characterised by rounded heterogeneous clasts in an aphanitic matrix, is only found in proximity to the Sudbury Impact crater. The distribution of the second, primarily sediment derived, type of breccia, as seen at Whitefish Falls, is strongly associated with mapped faults and regional-scale basement discontinuities, as defined by gravity and magnetic data. Since this type of breccia is present throughout the entire Huronian sedimentary sequence, the term “Huronian Breccia” is more appropriate. This breccia is not the result of a single geological event but rather episodes of fault activity, as the geometry of the Huronian basin evolved over time.
Syntheses of D-glucamine and N-methyl-D-glucamine modified chitosan for boron adsorption
Authors: Kurashina Masashi , Li Haoyuan , Shiba Keita , Morishita Yuta , Shibata Kazuki , Yasuzawa Mikito , Quyen Ho Hong
Published: April 2022

Two types of biodegradable chitosan-base boron adsorbents were synthesized by introducing D-glucamine and N-methyl-D-glucamine functional groups. Structural analysis was carried out using 1H-NMR. The maximum boron adsorption values were 3.5 mg g[Formula: see text] (equilibrium concentration, [Formula: see text] ppm), and 7.3 mg g[Formula: see text] ([Formula: see text] ppm) for D-glucamine and N-methyl-D-glucamine type chitosan adsorbents, respectively. The obtained boron adsorption capacity of N-methyl-D-glucamine modified chitosan was found to be 7.3 mg g[Formula: see text] ([Formula: see text] ppm) higher than that of the boron absorbent Amberlite IRA743. Thus, the biodegradable [Formula: see text]-methyl-D-glucamine-modified chitosan synthesized in this study is expected to be useful as a commercial product.
High-Performance 32-Bit Parallel Hybrid Adder Design Using RNS and Hybrid PTL/CMOS Logic
Authors: Khairnar Avadhoot , Chauhan Bhavuk , Sharma Geetanjali , Joshi Amit M.
Published: April 2022

Adders are one of the essential blocks of Arithmetic Logic Unit (ALU), addressing the memory, table indices and many more such types of applications. The speed of the adder unit more often decides the performance of CPU (Central Processing Unit) and GPU (Graphics Processing Unit) for graphics applications. The high-speed design is a very important performance parameter speed that too with less implementation area and low power consumption. In this paper, the author proposes a novel 32-bit Residue Hybrid Adder (RHA) using the Residue Number System (RNS) and implemented using a Hybrid CMOS/PTL logic style. An RNS has the advantage of representing a large integer using a set of few smaller integers to make computation more efficient and effective. On the other side, parallel prefix adders provide faster execution time as it performs the operation in parallel. With our paper, it is evident that RHA gives better performance in terms of delay, power consumption and area for arithmetic operations. The experimental analysis has been performed using the EDA tool on 45-nm CMOS technology. The power, delay and power delay product (PDP) performance parameters are compared with the existing adders and the results show that, thanks to smaller modules, proposed units have both smaller area and delay by up to 45% and 41%, and, consequently, they allow achieving up to over 46% power saving, respectively.
OPTIMAL CONTROL OF GENETIC DIVERSITY IN THE MORAN MODEL WITH POPULATION GROWTH
Authors: BONNEUIL NOËL
Published: April 2022

In the Moran model of drift and selection of a mutant allele with population growth, instead of examining the consequences of pre-specified selection and population growth, the coexistence of the wild allele and the mutant allele becomes the maximization of the expected sojourn time in a given set. The process is controlled by the additional mortality of the mutant and by population growth. This makes it possible to retroactively assign fitness values as functions of the constraints, thus guiding a conservation policy or the achievement of a wishful proportion of mutants. This also gives the optimal conditions that have allowed an observed coexistence.
IMPACT OF INDIUM DOPING ON ZnO THIN FILM SUBJECTED TO APPROPRIATE UHV TREATMENT CHARACTERIZED BY XPS, XRD, AND PL TECHNIQUES
Authors: HAMEURLAINE EDHAWYA , GUEZZOUL M’HAMED , BOUSLAMA M’HAMMED , OUERDANE ABDELLAH , DERRI AMIRA , BEDROUNI MAHMOUD , BENSASSI KADDA BENMOHKTAR , BAIZID ABDELHAK , ABDELKRIM MAHFOUD , KHAROUBI BACHIR
Published: April 2022

The chemical composition, crystalline structure and optical properties of un-doped ZnO (UZO) and indium (6%)-doped ZnO (IZO) thin films grown on Si substrate were studied using X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and photoluminescence (PL) techniques. The results are complementary and confirm each other. The surface is cleaned using checked ultra-high vacuum (UHV) treatment (argon ion sputtering followed by successive heating). For IZO, the XPS analysis displays that the indium incorporates in the ZnO matrix to form the In-O-Zn-type chemical bonds. The PL of UZO reveals structural defects, including oxygen interstitial (Oi), oxygen vacancies (VO), zinc vacancies (VZn) and interstitial zinc (Zni), and they decrease with the In doping and UHV treatment. For IZO, the PL measurements show the great interest of UHV treatment to stimulate the incorporation of indium into the ZnO matrix. There is an increase in the UV emission intensity and improvement of its physical structure. The In (6%) doping of ZnO is convenient to compensate the zinc vacancies (VZn), eliminate Zni and VO, and ensure the structural homogeneity of IZO film. All the detected peaks of the XRD patterns are matched to the wurtzite crystalline structure for both UZO and IZO thin films grown mainly along the (002) orientation plane.
RELATIONSHIP BETWEEN MICROSTRUCTURE, MECHANICAL PROPERTIES AND WEAR BEHAVIOR OF FRICTION STIR PROCESSED AZ31B ALLOY UNDER VARIOUS MEDIUM
Authors: SANKAR R. , RATHINASURIYAN C. , PUVIYARASAN M. , KUMAR V. S. SENTHIL
Published: April 2022

Plates of AZ31B were friction stir processed in three different environments, such as liquid nitrogen, water and air with a rotational speed of 1200[Formula: see text]rpm and feed rate of 90[Formula: see text]mm/min. Microstructural studies were carried out using optical and electron microscopes, phase identification was performed using X-ray diffraction, and all specimens were tested for hardness, tensile and wear. An examination of wear debris morphology was carried out. Under cryogenic, water and air mediums, grain refinement was achieved at 1.89, 2.23 and 18.23[Formula: see text]μm, respectively. The specimen using cryogenic medium displayed greater tensile strength and elongation than the water medium. Dissolution of consistently refined grains and secondary Mg17 Al12 particles was observed after FSP underwater and cryogenic medium, resulting in a significant increase in microhardness. This surface hardening produced a significant benefit for the friction and wear behavior of the magnesium as measured by pin-on-disc configuration using a universal tribometer. With a cryogenic cooling medium, the friction coefficient is reduced by approximately 23% and the wear rate is reduced by 8% in comparison to AFSP.
Personalized Recommendation Method of Entrepreneurial Service Information Based on Blockchain
Authors: Guo Shuzhe , Zhu Xiaolei , Liu Yang , Han Jianwei
Published: April 2022

In order to improve the effect of personalized recommendation of entrepreneurial service information, this paper combines blockchain technology to improve personalized recommendation algorithm. Moreover, for these four types of incentive mechanisms, this paper establishes corresponding income models, and further derives the optimal weights for each type of incentive mechanism. Finally, this paper designs a personalized recommendation system of entrepreneurial service information based on blockchain, and verifies the performance of the personalized recommendation system of entrepreneurial service information based on blockchain, and evaluates its data mining and recommendation effects based on simulation research. Through experimental research, we know that the personalized recommendation system of entrepreneurial service information based on blockchain can provide entrepreneurs with more reliable information services.
Effective Integration of ZigBee Communication Technology and Internet of Things Technology
Authors: Zhang Lili
Published: April 2022

ZigBee technology is a representative standard of wireless communication technology with very low complexity, short distance, low rate, low power consumption and low cost. Internet of Things technology is the development trend. In order to achieve the effective integration of ZigBee communication technology and Internet of Things technology, improve the real-time transmission efficiency and form an exclusive communication system. This paper carries out wireless voice communication through the integration of ZigBee technology and Internet of Things technology, and puts forward the research topic of wireless voice communication. The ZigBee technology and the Internet of Things are organically integrated through the clustering algorithm, the shortcomings of the Internet of Things technology are solved by using the advantages of ZigBee, the relevant model is constructed, the designed relevant algorithms are grouped, and the efficiency of the fused algorithm is compared with the algorithm before the fusion. The experimental results show that in the packet delivery rate experiment, the delivery rate of the algorithm is very high, and the speed can reach 97% at 20m/s. At the same time, the experimental results also show that the control overhead of the AODV protocol is significantly greater than that of the AODVjr protocol, and the AODV protocol can save at least 16% of the cost compared with the AODVjr protocol. And when the speed increases to a certain extent, the difference in control overhead between the two will become larger and larger.
On decay of entropy solutions to multidimensional conservation laws in the case of perturbed periodic initial data
Authors: Panov Evgeny Yu.
Published: April 2022

Under a precise genuine nonlinearity assumption we establish the decay of entropy solutions of a multidimensional scalar conservation law with merely continuous flux and with initial data being a sum of periodic function and a function vanishing at infinity (in the sense of measure).
Cooperative Technology Innovation Factors Identification and Analysis in the Manufacturing Virtual Industry Cluster
Authors: Chen Yiming , Wei Qiannan , Huang Xinyi , Deng Shaohong
Published: April 2022

A manufacturing virtual industry cluster (MVIC) is a complex system composed of multiple companies or organizations. In MVIC, there are many influencing factors on cooperative technology innovation, and the factors are interrelated. Companies in MVIC need to clarify the action mechanism of various influencing factors when conducting cooperative technology innovation. Based on literature research, 13 main influencing factors of cooperative technology innovation in MVIC are identified. The hierarchical structure model and driving power-dependence matrix of the influencing factors are constructed by the Interpretation Structure Model (ISM) and Matrix of Cross Impact Multiplication Applied to a Classification (MICMAC) method (the cross-effect matrix multiplication) to clarify the influence mechanism of each influencing factor on the cooperative technology innovation in MVIC. Strategic suggestions for promoting cooperative technology innovation in MVIC are proposed.