bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical and Clinical Role of Coenzyme Q10 Supplementation in
Various Pathological States
Authors: Rajesh Kumar , Khan M I , Mahesh Prasad , Kumar Srivastav Ritesh , Kumar Srivastav Shiv
Published: June 2022

Coenzyme Q10 (CoQ10) is an efficient antioxidant produced endogenously in a
living organism. It acts as an important cofactor in the electron transport
system of mitochondria and reported as a safe supplement in humans and animals
with minimal adverse effect. CoQ10 is found naturally, as a trans configuration,
chemical nomenclature of which is 2,3- dimethoxy-5- methyl-6-decaprenyle
-1,4-benzoquinone. It is found in the body in two forms. In quinone form
(oxidized form), it serves as an electron transporter that transfers the
electrons in the electron transport chain between various complexes, and in
ubiquinol form (reduced form), it serves as potent antioxidants by scavenging
free radicals or by tocopherol regeneration in the living organism. Its primary
roles include synthesis of adenosine triphosphate (ATP), stabilizes lipid
membrane, antioxidant activity, cell growth stimulation, and cell death
inhibition. CoQ10 has shown a variety of pharmacological and clinical effects
including neuroprotective, hepatoprotective, anti-atherosclerotic,
anticonvulsant, antidepressant, anti-inflammatory, antinociceptive,
cardiovascular, antimicrobial, immunomodulatory, and various effects on the
central nervous system. Present review has set about to bring updated
information regarding to clinical and preclinical activities of CoQ10, which may
be helpful to researchers to explore a new bioactive molecules for various
therapeutic application.
Entwicklung und Evaluation eines Simulators für die endoskopische Nasennebenhöhlenoperation
Authors: Pößneck Antje , Ludwig Alexandra Annemarie , Burgert Oliver , Nowatius Edgar , Maass Heiko , Çakmak Hüseyin Kemal , Dietz Andreas
Published: June 2022

Hintergrund Endoskopische Operationsverfahren haben sich als Goldstandard in der Nasennebenhöhlen-(NNH-)Chirurgie etabliert. Den sich daraus ergebenden Herausforderungen für die chirurgische Ausbildung kann durch den Einsatz von Virtuelle-Realität-(VR-)Trainingssimulatoren begegnet werden. Bislang wurde eine Reihe von Simulatoren für NNH-Operationen entwickelt. Frühere Studien im Hinblick auf den Trainingseffekt wurden jedoch nur mit medizinisch vorgebildeten Probanden durchgeführt oder es wurde nicht über dessen zeitlichen Verlauf berichtet.

Methoden Ein NNH-CT-Datensatz wurde nach der Segmentierung in ein 3-dimensionales, polygonales Oberflächenmodell überführt und mithilfe von originalem Fotomaterial texturiert. Die Interaktion mit der virtuellen Umgebung erfolgte über ein haptisches Eingabegerät. Während der Simulation wurden die Parameter Eingriffsdauer und Fehleranzahl erfasst. Zehn Probanden absolvierten jeweils eine Trainingseinheit bestehend aus je 5 Übungsdurchläufen an 10 aufeinanderfolgenden Tagen.

Ergebnisse Vier Probanden verringerten die benötigte Zeit um mehr als 60% im Verlauf des Übungszeitraums. Vier der Probanden verringerten ihre Fehleranzahl um mehr als 60%. Acht von 10 Probanden zeigten eine Verbesserung bezüglich beider Parameter. Im Median wurde im gesamten gemessenen Zeitraum die Dauer des Eingriffs um 46 Sekunden und die Fehleranzahl um 191 reduziert. Die Überprüfung eines Zusammenhangs zwischen den 2 Parametern ergab eine positive Korrelation.

Schlussfolgerung Zusammenfassend lässt sich feststellen, dass das Training am NNH-Simulator auch bei unerfahrenen Personen die Performance beträchtlich verbessert, sowohl in Bezug auf die Dauer als auch auf die Genauigkeit des Eingriffs.
Adverse Event Following Immunization (AEFI) in Children: An Analysis of Reporting in VigiAccess
Authors: Pandey Diksha , Mehta Geetika , Sachdeva Monika , Tripathi Rashmi
Published: June 2022

Introduction It is an indubitable fact that vaccination has been instrumental in the eradication and prevention of the deadliest diseases worldwide. Continuous vaccine safety surveillance is helpful to counter the negative perception and thus allay the fear of Adverse Events Following Immunization (AEFI) in the general public. VigiAccess, the WHO global database of reported side effects of medicinal products, can be accessed by the public at large. The objective of this study is to assess the characteristics of AEFIs of the commonly used vaccines in children in VigiAccess.

Materials and Methods VigiAccess was thoroughly explored for the categories, number, and types of AEFIs of commonly used vaccines among children that are reported in five continents between 2011 and 2021.

Results After a comprehensive analysis in VigiAccess, 27 kinds of AEFIs were discovered. For the nine vaccines, a total of 1,412,339 AEFIs were found. The most prevalent AEFIs were general disorder and administration site condition (436,199 or 30%). The majority of AEFIs are found in America, with Europe, Oceania, Asia, and Africa following closely behind. Girls of age from 27 days to 23 months had the highest number of AEFIs. The highest number of AEFIs was recorded in the year 2018.

Conclusion America has the maximum, whilst Africa has the least AEFI. Few AEFIs were caused by the measles vaccination, while the majority were related to the general disorder and administration site condition. Data synchronization in VigiAccess needs to be enhanced to improve its dependability.
A Practical Approach to 6H-Indol-6-ones Enables the Formal Synthesis of γ-Lycorane
Authors: Zhan Rui , Shao Li-Dong , Chen Yang , Hu Xin-Ting , Xie Xiao-Yan , Li Dashan , Zheng Chun-Xia , Zhang You-Xi , Wang Wen-Jing
Published: June 2022

We represented herein a two-step synthesis of 1-methyl-6H-indol-6-one which is an N-containing 6/5 fused bicyclic building blocks in Amaryllidaceae alkaloids. The key step featured is a ‘one-pot’ ozonolysis/reductive amination/cyclization of allylated cyclohexa-1,3-dione to give bicyclic compounds. Moreover, the formal total synthesis of natural product γ-lycorane could be achieved through a photo-promoted cyclization/oxidation cascade reaction from the resulting bicyclic intermediate.
Orthostatic Myoclonic Jerks in a Case of Hashimoto's Encephalopathy
Authors: Singh Amit Shankar , Sidhu Arshdeep Singh
Published: June 2022

Hashimoto's encephalopathy (HE) is an uncommon syndrome with the characteristic triad of positive antithyroid antibodies (most commonly antibodies to thyroid peroxidase), response to steroids, and clinical picture presenting either as stroke-like pattern of focal neurological deficit or slowly progressive cognitive impairment. Myoclonus or tremors, seizures, and psychosis are other associated features which can be seen in HE. Herein, we report a girl with an uncommon presentation of orthostatic axial and myoclonic jerks in bilateral lower limbs in a case of HE.
Predisposing Factors for Recurrent Aphthous Stomatitis among Undergraduate Dental Students
Authors: Rahmadhany Indriasari Putri , Mahdani Fatma Yasmin , Surboyo Meircurius Dwi Condro , Parmadiati Adiastuti Endah , Cecilia Pamela Handy , Sukmawati Natasya Fauzia
Published: June 2022

Objectives The prevalence of recurrent aphthous stomatitis (RAS) among the general population worldwide is 20%. This study aims to discover any correlations between RAS predisposing factors and the gender and year of study of undergraduate dental students at the Faculty of Dental Medicine at Airlangga University.

Methods A cross-sectional analytical study using simple random sampling was performed. The respondents answered seven questions on a self-reported online questionnaire set up using Google Forms. Chi-square analyses were conducted to determine any correlation between RAS predisposing factors and the gender and year of study of the students.

Results The highest predisposing factors for RAS in undergraduate dental students were local trauma (77.7%) followed by stress (71.3%) and nutritional deficiencies (41.5%). Stress correlated strongly with the year of study (p = 0.015). There was no correlation between gender and RAS predisposing factors (p > 0.05).

Conclusion There was a correlation between stress, one of the predisposing factors for RAS, and the year of study, but there was no correlation between gender and RAS predisposing factors including local trauma, stress, nutritional deficiency, genetics, allergies, and systemic diseases.
Characteristics of School Injuries Presenting to the Emergency Department
Authors: Özdemir Serdar , Akça Hatice Şeyma , Algın Abdullah , Kokulu Kamil , Özkan Abuzer
Published: June 2022

Background School injuries account for approximately one-fifth of pediatric injuries. We aimed to investigate the frequency and severity of school injuries among school-aged children and determine clinical diagnoses and surgery requirement data.

Methods In this prospective study, children who were admitted to the emergency department due to school accidents over a 5-month period were included. Demographics, activity during trauma, mechanism of trauma, nature, severity, emergency department outcomes, and surgery requirement were evaluated.

Results The study included a total of 504 school-aged children, of whom 327 (64.9%) were male and 177 (35.1%) were female. Of the children, 426 (84.5%) had no evidence of injury or minor injury, while 78 (15.5%) had moderate or severe injury. There was a statistically significant difference between these two groups in terms of gender (p = 0.031). Of the 78 children with moderate or severe injuries, 45 had extremity fractures, 18 had lacerations, 5 had maxillofacial injuries, 4 had cerebral contusion, 1 had lung contusion, and 1 had cervical soft-tissue damage. Two patients with fractures and two with eyelid lacerations were treated surgically, and four patients with brain contusion were hospitalized for a close follow-up.

Conclusion This study revealed that the most common moderate or severe injuries in school accidents referred to emergency department were distal radius fractures and lacerations.
Severe Congenital Myopathy and Neuropathy with Congenital Cataracts due to GFER Variant: A Neuropathological Study
Authors: Sanchez-Marco Silvia Beatriz , Pierre Germaine , Sharples Peta , Love Seth , Urankar Kathryn , Hilliard Tom , Lunt Peter , Churchill Amanda , Aungraheeta Riyaad , Dallosso Anthony , Evans Julie , Williams Maggie , Majumdar Anirban
Published: June 2022

We describe the clinical, muscle and nerve biopsy, and genetic findings in a 10-year-old girl with a profound and rapid global regression. She presented during neonatal period with hypotonia, followed by weakness in the facial, bulbar, respiratory, and neck flexor muscles. She developed bilateral cataracts at 4 months of age and started to regress. Quadriceps muscle biopsy revealed extensive fiber atrophy but sparing of some, predominantly type 1, fibers. Sural nerve biopsy showed depletion of myelinated and unmyelinated fibers; most remaining myelinated fibers were of small caliber. Neuroimaging revealed global brain atrophy. Although the investigations indicated a multisystem disorder, extensive genetic and metabolic investigations were negative. She was tracheostomy- and ventilator-dependent for most of her life. The child died at 10 years of age. Further deoxyribonucleic acid analysis undertaken via whole genome sequencing revealed a novel pathogenic GFER sequence variant consistent with the patient's clinical presentation.
Solid-state performance of a meta-GGA screened hybrid density functional constructed from Pauli kinetic enhancement factor dependent semilocal exchange hole
Authors: Jana Subrata , Constantin Lucian A. , Śmiga Szymon , Samal Prasanjit
Published: June 2022

The semilocal form of an exchange hole is highly useful in developing non-local range-separated hybrid density functionals for finite and extended systems. The way to construct the conventional exact exchange hole model is based on either the Taylor series expansion or the reverse engineering technique from the corresponding exchange energy functional. Although the latter technique is quite popular in the context of generalized gradient approximation (GGA) functionals, the same for the meta-GGA functionals is not so much explored. Thus, in this study, we propose a reverse-engineered semilocal exchange hole of a meta-GGA functional, which only depends on the meta-GGA ingredient α (also known as the Pauli kinetic energy enhancement factor). The model is subsequently used to design the short-range-separated meta-GGA hybrid density functional. We show that the present method can be successfully applied for several challenging problems in the context of solids, especially for which the GGA based hybrid fails drastically. This assessment proves that the present functional is quite useful for materials sciences. Finally, we also use this method for several molecular test cases, where the results are also as comparative as its base semilocal functional.
Attention and masking embedded ensemble reinforcement learning for smart energy optimization and risk evaluation under uncertainties
Authors: Sogabe Tomah , Malla Dinesh Bahadur , Chen Chih-Chieh , Sakamoto Katsuyoshi
Published: June 2022

Integrating residential-level photovoltaic energy generation and energy storage for the on-grid system is essential to reduce electricity use for residential consumption from the grid. However, reaching a reliable and optimal control policy is highly challenging due to the intrinsic uncertainties in the renewable energy sources and fluctuating demand profile. In this work, we proposed and designed an ensemble deep reinforcement learning (DRL) algorithm combined with risk evaluation to solve the energy optimization problem under uncertainties. Meanwhile, the attention and masking layer, the state-of-the-art natural language processing techniques, were incorporated into the algorithm to handle the issue of hard constraints, which are frequently encountered in the renewable energy optimization problem. To the best of our knowledge, this work is the first attempt to tackle the energy optimization problem under uncertainty using a scenario-based ensemble DRL approach with a risk evaluation. Through a well-designed single household microgrid energy management system, we found that the attention and masking layer played a crucial role in fulfilling the hard constraint. The ensemble DRL with the increased number of agents showed a significantly improved energy management policy leading to ∼75% of the cost reduction compared with those obtained by using conventional DRL with a single agent. The risk evaluation revealed that the current ensemble DRL approach possessed a high-risk/high-profit feature, which could be significantly improved by designing a risk-aware reward function in future investigations.
A model of droplet evaporation: New mathematical developments
Authors: Tonini S. , Cossali G. E. , Shchepakina E. A. , Sobolev V. A. , Sazhin S. S.
Published: June 2022

A previously developed model for mono-component droplet evaporation is revisited using new mathematical tools for its analysis. The analysis is based on steady-state mass, momentum, and energy balance equations for the vapor and air mixture surrounding a droplet. The previously obtained solution to these equations was based on the assumption that the parameter ε (proportional to the squared ratio of the diffusion coefficient and droplet radius) is equal to zero. The analysis presented in the paper is based on the method of integral manifolds, and it allowed us to present the droplet evaporation rate as the sum of the evaporation rate predicted by the model based on the assumption that ε=0 and the correction proportional to ε. The correction is shown to be particularly important in the case of small water and methanol droplets (diameters less than 5 μm) evaporating in air at low pressure (0.1 atm.). In this case, this correction could reach 35% of the original evaporation rate. In the case of evaporation of relatively large droplets (with radii more than 10 μm) in air at atmospheric and higher pressures, these corrections are shown to be small (less than 10−3 of the evaporation rate predicted by the model based on the assumption that ε=0).
The unified transform method to the high-order nonlinear Schrödinger equation with periodic initial condition
Authors: Liu Leilei , Zhang Weiguo , Xu Jian , Guo Yuli
Published: June 2022

In this paper, we study the high-order nonlinear Schrödinger equation with periodic initial conditions via the unified transform method extended by Fokas and Lenells. For the high-order nonlinear Schrödinger equation, the initial value problem on the circle can be expressed in terms of the solution of a Riemann–Hilbert problem. The related jump matrix can be explicitly expressed based on the initial data alone. Furthermore, we present the explicit solution, which corresponds to a one-gap solution.
On the Jet Structures of GRB 050820A and GRB 070125
Authors: Li Xin-Yu , He Hao-Ning , Wei Da-Ming
Published: June 2022

We present the broadband numerical modeling of afterglows for two remarkably bright long gamma-ray bursts (GRBs), GRB 050820A and GRB 070125, with a wide range of observations from the radio band to the X-ray band. In our work, we fit light curves and constrain physical parameters using a standard forward shock model from the afterglowpy Python package, considering different jet structures and the jet lateral expansion. For GRB 050820A, the constrained jet is close to a top-hat jet with an extremely small half opening angle of about 0.015 rad, and the circumburst matter density is as small as 10−7 cm−3, which suggests that this peculiar long GRB might originate from metal-poor stars with low mass-loss rates. To explain the late time optical light curves of GRB 070125, the effects of the lateral expansion and the participation factor of electrons that are accelerated by the shock have to be taken into account. The constrained results for GRB 070125 show that the jet is also close to a top-hat jet with a half opening angle of about 0.1 rad, the viewing angle is about 0.05 rad, the circumburst density is about 10 cm−3, and the participation factor is about 0.1. The jet energy of the two bursts is required to be ∼1051–1052 erg, which can be produced by a millisecond magnetar or a hyper-accreting black hole.
Short- and medium-term effect of inhaled corticosteroids on exhaled breath biomarkers in severe asthma
Authors: Alahmadi Fahad H , Wilkinson Max , Keevil Brian , Niven Rob , Fowler Stephen J
Published: June 2022

Inhaled corticosteroids (ICS) are the mainstay of therapy in asthma, but benefits vary due to disease heterogeneity. Steroid insensitivity is a particular problem in severe asthma, where patients may require systemic corticosteroids and/or biologics. Biomarkers sensitive to ICS over a short period of time could inform earlier and more personalised treatment choices. To investigate how exhaled breath biomarkers change over two-hours and one-week following monitored ICS dosing in severe asthma patients with evidence of uncontrolled airway inflammation. Patients with severe asthma and elevated fractional exhaled nitric oxide (FeNO) (⩾45 ppb, indicative of active airway inflammation) were recruited. Exhaled breath biomarkers were evaluated using (FeNO), exhaled breath temperature (EBT), particles in exhaled air (PExA) and volatile organic compounds (VOCs). Samples were collected over 2 h following observed inhalation of 1000 mcg fluticasone propionate, and at a second visit 1 week after taking the same dose daily via an inhaler monitoring device that recorded correct actuation and inhalation. Changes in parameters over 2 h were analysed by the Friedman test and 1 week by Wilcoxon’s test (p-value for significance set at 0.05; for VOCs false discovery rate q of 0.1 by Benjamini–Hochberg method applied). 17 participants (9 male) were recruited, but three could not complete PExA and two FeNO testing, as they were unable to comply with the necessary technique; complete datasets were available from 12 (9 male) with median (interquartile range) age 45 (36–59) yrs. EBT (p < 0.05) and levels of six VOCs (q < 0.1) fell over the 2 h after high dose ICS; there were no changes in FeNO or PExA. After one week of using high dose ICS, there were falls in FeNO, EBT and two VOCs (p < 0.05), but no changes in PExA. Reduction in EBT over the short and medium term after high dose ICS may reflect airway vascular changes, and this, together with the observed changes in exhaled VOCs, merits further investigation as potential markers of ICS use and effectiveness.
Optimization of tribological behaviour of TiO2 nanoparticles reinforced AA7178 alloy matrix using ANN and Taguchi’s methodology
Authors: Bharat Nikhil , Bose P S C
Published: June 2022

The investigation of tribological behaviour of AA7178 base alloy matrix reinforced with varying weight percentage of nano TiO2 particles (0,1,2 and 3%) using artificial neural network (ANN) and Taguchi is presented in this paper. Scanning Electron Microscope(SEM) with Energy Dispersive Spectroscopy (EDAX) was used to study the microstructural as well as wear behaviour of the nanocomposite. SEM images confirm that abrasive and adhesive wear was responsible for the worn-out surface. ANN with the Taguchi model was used to obtain the best input process parameters (sliding speed, distance, load and weight percentage) to minimize the output values (Coefficient of friction and wear rate). The coefficient of friction and wear rate were mainly affected from the weight percentage of nano TiO2 by 60.95% and 57.33%, respectively. The efficiency of ANN model was better compared to Taguchi model.
Pectolinarigenin reduces the expression of sterol regulatory element-binding proteins and cellular lipid levels
Authors: Zhang Yutao , Wan Changjian , Song Zijie , Meng Wei , Wang Songhua , Lan Zhou
Published: June 2022

Sterol regulatory element–binding proteins (SREBPs) are transcription factors that have important roles in the genes involved in lipid biosynthesis. In this study, it was found that the flavonoid pectolinarigenin, reduced the activity of SRE-containing fatty acid synthase (FAS) promoter and the mRNA expressions of SREBP target genes in human hepatoma (Huh-7) cells. Moreover, compared with other flavonoids, pectolinarigenin reduced the mature forms of SREBPs in a dose-dependent manner. The insulin-induced gene (INSIG) and proteasome were not involved in the pectolinarigenin-mediated reduction of mature forms of SREBPs. Pectolinarigenin also reduced the lipid contents in vitro. These results suggest that pectolinarigenin may inhibit lipogenesis through suppressing SREBP activity, at least partially, via the formation of SREBPs mature forms, thereby reducing the expression of their downstream genes related to lipogenesis. To the best of our knowledge, this is the first work that shows how pectolinarigenin affects cellular lipid levels by affecting SREBPs.
Reflecting on community development research: how peer researchers influence and shape community action projects
Authors: Arnull Elaine , Kanjilal Mahuya
Published: June 2022

This paper explores how the selection of peer researchers influences and shapes peer research projects. It draws on two empirical studies formed from two community action projects in England. Peer research is a method for involving young people as coresearchers within their community or in specific settings such as educational environments and the two projects recruited school children of different ages and ethnic backgrounds; in both cases they were representative of the potential participant population. One project (Community House) was based in a junior school setting and concentrated on evaluating a community centre project. The second project (Knife Angel: Hear My Voice) was a youth work setting and brought together a group of young people to explore an intervention aimed at impacting crime and violence in the local community.

This paper discusses how the demographic characteristics of the peer researchers shaped, influenced and impacted the success of both community action projects. We discuss how children and young people bring their unique skills to preparing the questionnaire and dissemination. Using researcher reflexivity, we consider the methodological implications of the findings and contribute to theory building about community action and the impact of participatory research.
Presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies Among Vietnamese Healthcare Workers by Dosing Interval for ChAdOx1 nCoV-19 Vaccine
Authors: Vu Dien M , Vu Diep T B , Do Thuy T T , Olmsted Allison E , Dao Bach H , Thai Truc T , Nguyen Chi L , Le Nhung T T , Le Tuan A , Bui Hien T T , Pham Thach N , Moore Matthew R
Published: June 2022

Background

Before the SARS-CoV-2 Delta variant arrived in Vietnam, case rates suggested seroprevalence of SARS-CoV-2 was low. Beginning in March 2021, we assessed different dosing schedules and adverse events following immunization (AEFIs) for ChAdOx1 nCoV-19 vaccine among healthcare workers (HCWs).

Methods

We performed a prospective cohort study to estimate the prevalence of IgG antibodies to SARS-CoV-2 before and after ChAdOx1 nCoV-19 vaccination. We conducted antibody testing among HCWs in February 2021 (baseline), before the second dose (June–July 2021), and 1 and 3 months after the second dose. We detected antibodies to SARS-CoV-2 using Tetracore® FlexImmArray™, and surrogate neutralizing antibodies using GenScript cPass™. Neither assay can distinguish natural from vaccine-induced antibodies. We assessed AEFIs through interview post–dose 1 and 1 month post–dose 2.

Results

Before vaccination, 1/617 participants (0.16%) had antibodies to SARS-CoV-2. Of these 617, 405 were vaccinated with ChAdOx1 nCoV-19 with 4–8- (60%), 9–12- (27%), or ≥13-week (13%) intervals between the 2 doses. Three months following series completion, 99% and 97% of vaccinated participants had ≥1 sample with detectable antibodies and surrogate neutralizing antibodies against SARS-CoV-2, respectively. We observed no significant differences among those with different dosing intervals at last follow-up. All participants reported PCR testing for SARS-CoV-2 during the study; 2 (0.5%) were laboratory-confirmed. AEFIs were more frequent post–dose 1 (81%) vs post–dose 2 (21%).

Conclusions

In this population, regardless of dosing interval, ChAdOx1 nCoV-19 induced antibodies within 3 months of the second dose. These findings may offer flexibility to policymakers when balancing programmatic considerations with vaccine effectiveness.
Improved anastomotic leakage rates after the “flap and wrap” reconstruction in Ivor Lewis esophagectomy for cancer
Authors: Slaman Annelijn E , Eshuis Wietse J , van Berge Henegouwen Mark I , Gisbertz Suzanne S
Published: June 2022

Anastomotic leakage after esophagectomy has serious consequences. In Ivor Lewis esophagectomy, a shorter and possibly better vascularized gastric conduit is created than in McKeown esophagectomy. Intrathoracic anastomoses can additionally be wrapped in omentum and concealed behind the pleura (“flap and wrap” reconstruction). Aims of this observational study were to assess the anastomotic leakage incidence after transhiatal esophagectomy (THE), McKeown esophagectomy (McKeown), Ivor Lewis esophagectomy (IL) without “flap and wrap” reconstruction, and IL with “flap and wrap” reconstruction. Consecutive patients undergoing esophagectomy at a tertiary referral center between January 2013 and April 2019 were included. Primary outcome was the anastomotic leakage rate. Secondary outcomes were postoperative outcomes, mortality, and 3-year overall survival. A total of 463 patients were included. The anastomotic leakage incidence after THE (n = 37), McKeown (n = 97), IL without “flap and wrap” reconstruction (n = 39), and IL with “flap and wrap” reconstruction (n = 290) were 24.3, 32.0, 28.2, and 7.2% (P < 0.001). THE and IL with “flap and wrap” reconstruction required fewer reoperations for anastomotic leakage (0 and 1.4%) than McKeown and IL without “flap and wrap” reconstruction (6.2 and 17.9%, P < 0.001). Fewer anastomotic leakages are observed after Ivor Lewis esophagectomy with “flap and wrap” reconstruction compared to transhiatal, McKeown and Ivor Lewis esophagectomy without “flap and wrap” reconstruction. The “flap and wrap” reconstruction seems a promising technique to further reduce anastomotic leakages and its severity in esophageal cancer patients who have an indication for Ivor Lewis esophagectomy.
Older People’s Neighborhood Perceptions Are Related to Social and Emotional Loneliness and Mediated by Social Network Type
Authors: Stephens Christine , Phillips Hannah
Published: June 2022

Background and Objectives

Loneliness among older people is a public health issue; however, there is very weak support for the efficacy of individually focused interventions. A public health model, which includes the environmental influence on the formation of social networks and protection from loneliness, and theoretical approaches differentiating between social and emotional loneliness, suggest the importance of neighborhoods in preventing loneliness. This approach was used to test the influence of neighborhood factors on loneliness and the mediating role of social networks.

Research Design and Methods

A questionnaire survey of 917 people aged 60–100 years was conducted in one region of Aotearoa/New Zealand to assess loneliness, social network types, social participation, marital status, gender, health, and four aspects of neighborhood perceptions.

Results

Social and emotional loneliness scores were regressed on predicted demographic and social variables, followed by perceptions of Housing Satisfaction, Neighborhood Accessibility, Neighborhood Security, and Neighborhood Social Cohesion. Neighborhood variables added significant explanation of variance in both social and emotional loneliness. Mediation tests using PROCESS showed that the effects of all neighborhood variables were mediated by Private-Restricted or Locally Integrated Network types on Social Loneliness only.

Discussion and Implications

These findings highlight the importance of neighborhood factors in relation to feelings of loneliness and the recognition of social network types as mediators of these relationships for social loneliness. The aspects of neighborhoods that prevent loneliness provide directions for planners and prevention programs. Interventions to prevent social loneliness can usefully and practicably focus on the housing and neighborhood environment.
High Neutralizing Antibody Levels Against Severe Acute Respiratory Syndrome Coronavirus 2 Omicron BA.1 and BA.2 After UB-612 Vaccine Booster
Authors: Guirakhoo Farshad , Wang Shixia , Wang Chang Yi , Kuo Hui Kai , Peng Wen Jiun , Liu Hope , Wang Lixia , Johnson Marina , Hunt Adam , Hu Mei Mei , Monath Thomas P , Rumyantsev Alexander , Goldblatt David
Published: June 2022

The highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has caused high rates of breakthrough infections in those previously vaccinated with ancestral strain coronavirus disease 2019 (COVID-19) vaccines. Here, we demonstrate that a booster dose of UB-612 vaccine candidate delivered 7–9 months after primary vaccination increased neutralizing antibody levels by 131-, 61-, and 49-fold against ancestral SARS-CoV-2 and the Omicron BA.1 and BA.2 variants, respectively. Based on the receptor-binding domain protein binding antibody responses, the UB-612 third-dose booster may lead to an estimated approximately 95% efficacy against symptomatic COVID-19 caused by the ancestral strain. Our results support UB-612 as a potential potent booster against current and emerging SARS-CoV-2 variants.
Pharmacodynamic evaluation of piperacillin/tazobactam versus meropenem against extended-spectrum β-lactamase-producing and non-producing Escherichia coli clinical isolates in a hollow-fibre infection model
Authors: Islam Kamrul , Sime Fekade B , Wallis Steven C , Bauer Michelle J , Forde Brian M , Harris Patrick , Shirin Tahmina , Habib Zakir H , Flora Meerjady S , Roberts Jason A
Published: June 2022

Background

Urosepsis caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. Carbapenems are commonly recommended for the treatment of ESBL infections; however, to minimize the emergence of carbapenem resistance, interest in alternative treatments has heightened.

Objectives

This study compared pharmacodynamics of piperacillin/tazobactam versus meropenem against ESBL-producing and non-producing E. coli clinical isolates.

Methods

E. coli isolates, obtained from national reference laboratory in Bangladesh, were characterized by phenotypic tests, WGS, susceptibility tests and mutant frequency analysis. Three ESBL-producing and two non-producing E. coli were exposed to piperacillin/tazobactam (4.5 g, every 6 h and every 8 h, 30 min infusion) and meropenem (1 g, every 8 h, 30 min infusion) in a hollow-fibre infection model over 7 days.

Results

Piperacillin/tazobactam regimens attained ∼4–5 log10 cfu/mL bacterial killing within 24 h and prevented resistance emergence over the experiment against ESBL-producing and non-producing E. coli. However, compared with 8 hourly meropenem, the 6 hourly piperacillin/tazobactam attained ∼1 log10 lower bacterial kill against one of three ESBL-producing E. coli (CTAP#173) but comparable killing for the other two ESBL-producing (CTAP#168 and CTAP#169) and two non-producing E. coli (CTAP#179 and CTAP#180). The 6 hourly piperacillin/tazobactam regimen attained ∼1 log10 greater bacterial kill compared with the 8 hourly regimen against CTAP#168 and CTAP#179 at 24 h.

Conclusions

Our study suggests piperacillin/tazobactam may be a potential alternative to carbapenems to treat urosepsis caused by ESBL-producing E. coli, although clinical trials with robust design are needed to confirm non-inferiority of outcome.
Identification of Chemical Constituents in Zhizhu Pills Based on UPLC-QTOF-MSE
Authors: Zheng Wei , Gao Ruxi , Wang Fanyi , Shan Guoshun , Gao Hui
Published: June 2022

Background

Zhizhu pills (ZZP) are a traditional Chinese medicine (TCM) prescription, mainly used for clinically treating digestive diseases such as functional dyspepsia, constipation, and peptic ulcer. However, the chemical constituents of ZZP have rarely been reported.

Objective

To establish an ultrahigh-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UPLC-QTOF-MSE) method for the identification of chemical constituents in ZZP, including individual herbs and a complicated Chinese medicinal formula.

Methods

The extracts of ZZP and its individual herb samples were analyzed by a UPLC-QTOF-MSE method on an ACQUITY UPLC HSS T3 column (100 × 2.1 mm id, 1.8 μm particle size) using a gradient elution of 0.1% formic acid in acetonitrile - 0.1% formic acid water (v/v) at a constant flow rate of 0.4 mL/min. With the MSE technique, both precursor ion and fragmentation information of compounds can be simultaneously acquired by alternating between low and high collision energy during a single chromatographic run. The data were analyzed on UNIFI.

Results

A total of 154 compounds, including 67 flavonoids, 17 coumarins, 11 terpenoids, 10 alkaloids, six limonoids, six sequiterpene lactones, and 37 other components, were ultimately identified based on accurate masses and fragmentation patterns in ZZP and its individual herbs.

Conclusions

This paper summarized fragmentation patterns of flavonoids, sequiterpene lactones, alkaloids, coumarins, and limonoids. A rapid, accurate, and comprehensive UPLC-QTOF-MSE method has been developed for the identification of chemical compounds and applied to simultaneously evaluate the quality and effectiveness of ZZP.

Highlights

A total of 154 compounds were ultimately identified in ZZP and its individual herbs by UPLC-QTOF-MSE; the fragmentation patterns of flavonoids, sequiterpene lactones, alkaloids, coumarins, and limonoids in ZZP and its individual herbs are summarized.
How copper can impact pig growth: comparing the effect of copper sulfate and monovalent copper oxide on oxidative status, inflammation, gene abundance, and microbial modulation as potential mechanisms of action
Authors: Forouzandeh Asal , Blavi Laia , Pérez Jose Francisco , D’Angelo Matilde , González-Solé Francesc , Monteiro Alessandra , Stein Hans H , Solà-Oriol David
Published: June 2022

The beneficial effect of elevated concentrations of copper (Cu) on growth performance of pigs has been already demonstrated; however, their mechanism of action is not fully discovered. The objective of the present experiment was to investigate the effects of including Cu from copper sulfate (CuSO4) or monovalent copper oxide (Cu2O) in the diet of growing pigs on oxidative stress, inflammation, gene abundance, and microbial modulation. We used 120 pigs with initial body weight (BW) of 11.5 ± 0.98 kg in 2 blocks of 60 pigs, 3 dietary treatments, 5 pigs per pen, and 4 replicate pens per treatment within each block for a total of 8 pens per treatment. Dietary treatments included the negative control (NC) diet containing 20 mg Cu/kg and 2 diets in which 250 mg Cu/kg from CuSO4 or Cu2O was added to the NC. On day 28, serum samples were collected from one pig per pen and this pig was then euthanized to obtain liver samples for the analysis of oxidative stress markers (Cu/Zn superoxide dismutase, glutathione peroxidase, and malondialdehyde, MDA). Serum samples were analyzed for cytokines. Jejunum tissue and colon content were collected and used for transcriptomic analyses and microbial characterization, respectively. Results indicated that there were greater (P < 0.05) MDA levels in the liver of pigs fed the diet with 250 mg/kg CuSO4 than in pigs fed the other diets. The serum concentration of tumor necrosis factor-alpha was greater (P < 0.05) in pigs fed diets containing CuSO4 compared with pigs fed the NC diet or the diet with 250 mg Cu/kg from Cu2O. Pigs fed diets containing CuSO4 or Cu2O had a greater (P < 0.05) abundance of genes related to the intestinal barrier function and nutrient transport, but a lower (P < 0.05) abundance of pro-inflammatory genes compared with pigs fed the NC diet. Supplementing diets with CuSO4 or Cu2O also increased (P < 0.05) the abundance of Lachnospiraceae and Peptostreptococcaceae families and reduced (P < 0.05) the abundance of the Rikenellaceae family, Campylobacter, and Streptococcus genera in the colon of pigs. In conclusion, adding 250 mg/kg of Cu from CuSO4 or Cu2O regulates genes abundance in charge of the immune system and growth, and promotes changes in the intestinal microbiota; however, Cu2O induces less systemic oxidation and inflammation compared with CuSO4.
Lost in Transition: A Significant Correction in Aldus Manutius’s Psalterion (1496/98)
Authors: Della Rocca De Candal Geri
Published: June 2022

Aldus Manutius (c. 1450–1515), one of the best-known printers of Renaissance Venice, was very eager to promote his editions as offering the highest editorial and typographical standards. But not even Aldus was immune to misprinting: in his Greek Psalterion (1496/98), for instance, an entire line of text went missing between gatherings. The error was spotted while the sheets were still being printed, resulting in two major types of corrections: stop-press (c. 15%), and manuscript (c. 85%), with the latter type often—but not always—in Aldus’s own hand. The article examines the actions taken by the Aldine press to tackle this major misprint, and address the question of how typographical flaws help us understand early printing practices.
Spectrum synthesis for radially pulsating stars with shocked atmospheres
Authors: Jeffery C Simon
Published: June 2022

spec_puls describes a suite of computer programs to simulate the emergent spectrum from a radially pulsating star. It combines a Christy-type non-linear pulsation code with classical stellar atmosphere codes. The principal aim is to interpret the dynamical spectrum of the radially pulsating extreme helium star V652 Herculis (V652 Her), which shows a strong shock at minimum radius. The components are general enough to treat other classes of radial pulsation. The theoretical spectrum from a shocked pulsation model shows line doubling, with the blue component emerging at standstill velocity and accelerating blueward. The doubling phase depends on line depth and parent ion. The behaviour of line cores post-shock points to a drop in the ionization temperature, although the gas temperature in the model remains high. Shock compression leads to phase-dependent strengthening of Stark-broadened line wings, with the far wings responding first. With velocity-, temperature-, and pressure-sensitive diagnostics, detailed tomography of the pulsation-driven shock in V652 Her seems possible. Even when no shock is present, the dynamical spectrum is significantly different from a model in hydrostatic equilibrium. Using the quasi-static approximation (e.g. at maximum radius) may lead to a considerable underestimate of the star’s mean effective temperature and surface gravity.
Gamma-ray light curves and spectra of classical novae
Authors: Leung Shing-Chi , Siegert Thomas
Published: June 2022

The nucleosynthesis in classical novae, in particular that of radioactive isotopes, is directly measurable by its γ-ray signature. Despite decades of observations, MeV γ-rays from novae have never been detected – neither individually at the time of the explosion, nor as a result of radioactive decay, nor the diffuse Galactic emission from the nova population. Thanks to recent developments in modelling of instrumental background for MeV telescopes such as INTEGRAL/SPI and Fermi/GBM, the prospects to finally detect these elusive transients are greatly enhanced. This demands for updated and refined models of γ-ray spectra and light curves of classical novae. In this work, we develop numerical models of nova explosions using sub- and near-Chandrasekhar CO white dwarfs as the progenitor. We study the parameter dependence of the explosions, their thermodynamics and energetics, as well as their chemical abundance patterns. We use a Monte Carlo radiative transfer code to compute γ-ray light curves and spectra, with a focus on the early time evolution. We compare our results to previous studies and find that the expected 511-keV-line flash at the time of the explosion is heavily suppressed, showing a maximum flux of only $10^{-9}\, \mathrm{ph\, cm^{-2}\, s^{-1}}$ and thus making it at least one million times fainter than estimated before. This finding would render it impossible for current MeV instruments to detect novae within the first day after the outburst. Nevertheless, our time-resolved spectra can be used for retrospective analyses of archival data, thereby improving the sensitivity of the instruments.
Excess Mortality Attributable to Hospital-Acquired Antimicrobial-Resistant Infections: A 2-Year Prospective Surveillance Study in Northeast Thailand
Authors: Lim Cherry , Teparrukkul Prapit , Nuntalohit Somboon , Boonsong Somsamai , Nilsakul Jiraphorn , Srisamang Pramot , Sartorius Benn , White Nicholas J , Day Nicholas P J , Cooper Ben S , Limmathurotsakul Direk
Published: June 2022

Background

Quantifying the excess mortality attributable to antimicrobial-resistant (AMR) bacterial infections is important for assessing the potential benefit of preventive interventions and for prioritization of resources. However, there are few data from low- and middle-income countries.

Methods

We conducted a 2-year prospective surveillance study to estimate the excess mortality attributable to AMR infections for all types of hospital-acquired infection (HAI), and included bacterial species that were both locally relevant and included in the World Health Organization priority list. Twenty-eight-day mortality was measured. Excess mortality and population attributable fraction (PAF) of mortality caused by AMR infections compared to antimicrobial-susceptible (AMS) infections, adjusted for predefined confounders, were calculated.

Results

We enrolled 2043 patients with HAIs. The crude 28-day mortality of patients with AMR and AMS infections was 35.5% (491/1385) and 23.1% (152/658), respectively. After adjusting for prespecified confounders, the estimated excess mortality attributable to AMR infections was 7.7 (95% confidence interval [CI], 2.2–13.2) percentage points. This suggests that 106 (95% CI, 30–182) deaths among 1385 patients with AMR infections might have been prevented if all of the AMR infections in this study were AMS infections. The overall PAF was 16.3% (95% CI, 1.2%–29.1%). Among the bacteria under evaluation, carbapenem-resistant Acinetobacter baumannii was responsible for the largest number of excess deaths. Among all types of infection, urinary tract infections were associated with the highest number of excess deaths, followed by lower respiratory tract infections and bloodstream infections.

Conclusions

Estimating and monitoring excess mortality attributable to AMR infections should be included in national action plans to prioritize targets of preventive interventions.

Clinical Trials Registration

NCT03411538.
The Relationship Between Antibiotic Agent and Mortality in Patients With Febrile Neutropenia due to Staphylococcal Bloodstream Infection: A Multicenter Cohort Study
Authors: Aleissa Muneerah M , Gonzalez-Bocco Isabel H , Zekery-Saad Sara , Kubiak David W , Zhang Eric M , Signorelli Jessie , Hammond Sarah P , Mohareb Amir M , Luskin Marlise R , Manne-Goehler Jennifer , Marty Francisco M
Published: June 2022

Background

Methicillin-susceptible Staphylococcus aureus (MSSA) is a common cause of bloodstream infection (BSI) in patients with febrile neutropenia, but treatment practices vary, and guidelines are not clear on the optimal regimen.

Methods

We conducted a multicenter retrospective cohort study of MSSA BSI in febrile neutropenia. We divided patients into 3 treatment groups: (1) broad-spectrum beta-lactams (ie, piperacillin-tazobactam, cefepime, meropenem); (2) narrow-spectrum beta-lactams (ie, cefazolin, oxacillin, nafcillin); and (3) combination beta-lactams (ie, both narrow- and broad-spectrum). We used multivariable logistic regression to compare 60-day mortality and bacteremia recurrence while adjusting for potential confounders.

Results

We identified 889 patients with MSSA BSI, 128 of whom had neutropenia at the time of the index culture: median age 56 (interquartile range, 43–65) years and 76 (59%) male. Of those, 56 (44%) received broad-spectrum beta-lactams, 30 (23%) received narrow-spectrum beta-lactams, and 42 (33%) received combination therapy. After adjusting for covariates, including disease severity, combination therapy was associated with a significantly higher odds for 60-day all-cause mortality compared with broad spectrum beta-lactams (adjusted odds ratio [aOR], 3.39; 95% confidence interval [CI], 1.29–8.89; P = .013) and compared with narrow spectrum beta-lactams, although the latter was not statistically significant (aOR, 3.30; 95% CI, .80–13.61; P = .071).

Conclusions

Use of combination beta-lactam therapy in patients with MSSA BSI and febrile neutropenia is associated with a higher mortality compared with treatment with broad-spectrum beta-lactam after adjusting for potential confounders. Patients in this study who transitioned to narrow-spectrum beta-lactam antibiotics did not have worse clinical outcomes compared with those who continued broad-spectrum beta-lactam therapy.