bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbiological Production of Polyhydroxbutyrates From Renewable Sources
Authors: Rysbek A.B. , Kurmanbayev A.A.
Published: October 2021

Plastics play an important role in our daily lives and are used for various purposes. The industry of environmentally friendly products is actively developing in our time, including bioplastics, and much attention of scientists is attracted by biodegradable polymers such as polyhydroxyalacanoates or its subspecies polyhydroxybutyrates, which are synthesized by various microorganisms as a reserve substance, and are also the most acceptable replacement for conventional synthetic plastics. However, the cost of large-scale production of such a biodegradable polymer is not competitive with its wide distribution. Studies of the microbial production of polyhydroxybutyrates should be aimed at identifying cost-effective substrates, as well as determining the appropriate strain of the body for production. These biopolymers have a number of specific properties, such as biodegradability and compatibility with living body tissue, which opens up great opportunities for their use in practice. The final product of polyhydroxybutyrates biodegradation in the environment is water and carbon dioxide, and in a living organism 3-butobutyric acid. The main focus of this review was the production of bioplastics from various economical substrates using various types of bacteria.
Prospects for The Use of Thermotolerant Microorganisms for Remediation of Oil-Contaminated Soils
Authors: Aitkeldiyeva S.A. , Faizulina E.R. , Tatarkina L.G. , Alimbetova A.V. , Auezova O.N. , Spankulova G.A.
Published: October 2021

Most of the world's oil fields are concentrated in geographic areas with high temperature conditions. One of the main problems of remediation of territories in hot climates is the fact that high temperatures reduce the viscosity of oil and, thus, accelerate its diffusion into the soil. This greatly complicates the processes of soil cover restoration using conventional methods. An alternative can be bioremediation using the oil-oxidizing microorganisms that are resistant to high temperatures and low humidity. The presented review is devoted to the analysis of studies of thermotolerant microorganisms by scientists from different countries with the aim of using them in the remediation of contaminated soils from oil and oil products. The data on the influence of the main environmental factors, such as temperature, oxygen, pH, salinity, aeration, the presence of nutrients, etc., on the viability and vital activity of thermotolerant hydrocarbon-oxidizing microorganisms are presented. Examples of biochemical and molecular genetic characteristics of thermotolerant microorganisms are given. Their taxonomic diversity is shown, and examples of the degradation of individual oil components by active strains are given.
The Study of Bacteria-Destructors of Organic Pollution from Collection of Microorganisms
Authors: Kurmanbayev A.A , Baigonussova Zh. A.
Published: October 2021

To replenish the collection of microorganisms 125 strains of oil-decomposing bacteria were isolated. 34 bacterial isolates were isolated from enrichment cultures, consuming sodium dodecyl sulfate as the only carbon source. As a result, it was found that the most active were 20 isolates. 65 isolates of microorganisms were isolated from the reservoir waters of Western Kazakhstan, oil sludge and waste waters by the method of enrichment cultures. The most active were 47 isolates. It was found that the ability to dispose of oil was greatest in the isolate, which disposed of oil by 73%.  26 isolates capable of decomposing fat were isolated from wastewater in Astana. 16 Isolates revealed the highest lipase activity.
The Gompertz model revisited and modified using reaction networks: Mathematical analysis
Authors: Markov Svetoslav Marinov
Published: October 2021

In the present work we discuss the? usage of the framework of chemical reaction networks for the construction of dynamical models and their mathematical analysis. To this end, the process of construction of reaction-network-based models via mass action kinetics is introduced and illustrated on several familiar examples,? such as the exponential (radioactive) decay, the logistic and the Gompertz models. Our final goal is to modify the reaction network of the classic Gompertz model in a natural way using certain features of the exponential decay and the logistic models. The growth function of the obtained new Gompertz-type hybrid model possesses an additional degree of freedom (one more rate parameter) and is thus more flexible when applied to numerical simulation of measurement and experimental data sets. More specifically, the ordinate (height) of the inflection point of the new generalized Gompertz model can vary in the interval (0, 1/e], whereas the respective height of the classic Gompertz model is fixed at 1/e (assuming the height of the upper asymptote is one). It is shown that? the new model is a generalization of both the classic Gompertz model and the one-step exponential decay model.? Historically the Gompertz function has been first used for statistical/insurance purposes, much later this function has been applied to simulate biological growth data sets coming from various fields of science, the reaction network approach explains and unifies the two approaches.
Experiment and Codes to Support Safety Assessments for Sodium Fast Reactors (KASOLA, SOLTEC and KARIFA)
Authors: Hering Wolfgang , Fuchs Joachim , Onea Alexandru , Perez-Martin Sara , Schaub Thomas
Published: October 2021

The experimental liquid metal loops hosted within the Karlsruhe Sodium laboratory (KASOLA) comprise a set of facilities to study liquid metal flows for various types of energy applications ranging from room temperature conditions used for education and training and fundamental research up to challenges posed by multiphysics problems such as material–fluid interactions at high temperatures. Extreme conditions, such as sodium boiling, relevant to thermo-electric conversion or fast reactor safety are covered in a dedicated small-scale facility (Karlsruhe receiver test facility (KARIFA)). The complete experimental range is complemented by system code support and computational fluid dynamics (CFD) simulation. The outcome of the experiments is used for code validation and development allowing application not only on component but also on system level. The paper presents main experimental facilities and supporting computational codes used at KASOLA.
KPC-39-Mediated Resistance to Ceftazidime-Avibactam in a Klebsiella pneumoniae ST307 Clinical Isolate
Authors: Jousset Agnès B. , Oueslati Saoussen , Emeraud Cécile , Bonnin Rémy A. , Dortet Laurent , Iorga Bogdan I. , Naas Thierry
Published: October 2021

Resistance to the ceftazidime (CAZ)-avibactam (AVI) combination is increasingly being reported. Here, we report a CAZ-AVI-resistant
Klebsiella pneumoniae
strain belonging to the high-risk sequence type 307 (ST307) clone and producing
Klebsiella pneumoniae
carbapenemase 39 (KPC-39), a single-amino-acid variant of KPC-3 (A172T).
Macrodomain Binding Compound MRS 2578 Inhibits Alphavirus Replication
Authors: Mattila Sari , Merilahti Pirjo , Wazir Sarah , Quirin Tania , Maksimainen Mirko M. , Zhang Yuezhou , Xhaard Henri , Lehtiö Lari , Ahola Tero
Published: October 2021

Alphaviruses are positive-strand RNA viruses causing febrile disease. Macrodomain-containing proteins, involved in ADP-ribose-mediated signaling, are encoded by both host cells and several virus groups, including alphaviruses.
Identification of a Proteasome-Targeting Arylsulfonamide with Potential for the Treatment of Chagas’ Disease
Authors: Lima Marta L. , Tulloch Lindsay B. , Corpas-Lopez Victoriano , Carvalho Sandra , Wall Richard J. , Milne Rachel , Rico Eva , Patterson Stephen , Gilbert Ian H. , Moniz Sonia , MacLean Lorna , Torrie Leah S. , Morgillo Carmine , Horn David , Zuccotto Fabio , Wyllie Susan
Published: October 2021

Phenotypic screening identified an arylsulfonamide compound with activity against
Trypanosoma cruzi
, the causative agent of Chagas’ disease. Comprehensive mode of action studies revealed that this compound primarily targets the
T. cruzi
proteasome, binding at the interface between β4 and β5 subunits that catalyze chymotrypsin-like activity.
Evolutionary Insights into the Microneme-Secreted, Chitinase-Containing High-Molecular-Weight Protein Complexes Involved in
Plasmodium
Invasion of the Mosquito Midgut
Authors: Kaur Hargobinder , Pacheco M. Andreina , Garber Laine , Escalante Ananias A. , Vinetz Joseph M.
Published: October 2021

While general mechanisms by which
Plasmodium
ookinetes invade the mosquito midgut have been studied, details regarding the interface of the ookinete, specifically its barriers to invasion, such as the proteolytic milieu, the chitin-containing, protein cross-linked peritrophic matrix, and the midgut epithelium, remain to be understood. Here, we review our knowledge of
Plasmodium
chitinases and the mechanisms by which they mediate ookinetes crossing the peritrophic matrix.
Supplemental Material: Polychromatic polarization: Boosting the capabilities of the good old petrographic microscope
Authors: Cesare Bernardo , al. et
Published: October 2021

Description of the polychromatic polarizing microscope.
Method and Equipment for Infrared and Ultrasonic Thermographic Testing of Large-Sized Complex-Shaped Composite Products
Authors: Chulkov A. O. , Nesteruk D. A. , Shagdyrov B. I. , Vavilov V. P.
Published: October 2021

The robotic equipment for and the technique of combined thermal nondestructive testing (NDT) of large-sized products by zones with subsequent data synthesis are described. The effectiveness of the combination of two methods, infrared and ultrasonic thermographic testing, is shown by the example of the developed complex-shaped reference sample with 18 simulators of production and operational defects. The developed algorithms for the synthesis of test results, including spatial “matching” of a set of thermograms and automated flaw detection and defect characterization with the use of neural networks have illustrated the effectiveness of the proposed approach for practical application.
Acquired cryptorchidism: an unexpected consequence of inguinoscrotal lymphatic malformation treated with Eppikajutsuto
Authors: Uebayashi Elena Yukie , Ohno Koichi , Iwade Tamaki , Takada Narito
Published: October 2021

Lymphatic malformation (LM) that causes inguinoscrotal swelling is extremely rare. Surgery, sclerotherapy and pharmacotherapy have been reported as possible treatment options for LM. Recently, Eppikajutsuto (TJ-28), a traditional Japanese herbal medicine has emerged as therapeutic option for LM. We report the case of a 2-year-old boy who presented with a left inguinoscrotal swelling, which was diagnosed as retroperitoneal LM extending into the left scrotum. The surgical approach was less favourable, given the risk of damaging the testicular vasculature or the spermatic cord. Therefore, the patient received medical treatment with TJ-28. As a result, a volume reduction of 83% was obtained, as well as the unexpected consequence of the left testicle retracting into the inguinal area. Laparoscopic exploration was performed and a small bulge on the internal inguinal ring was detected. The patient’s acquired cryptorchidism was subsequently treated by orchidopexy.
Acute-onset chronic inflammatory demyelinating polyneuropathy after COVID-19 infection and subsequent ChAdOx1 nCoV-19 vaccination
Authors: Suri Vinit , Pandey Shishir , Singh Jyoti , Jena Amarnath
Published: October 2021

SARS-COV-2 predominantly results in a respiratory illness. However, it has also been associated with a wide range of neurological disorders including a broad range of immune neuropathies. These immune neuropathies associated with SARS-COV2 infection include Guillain-Barré syndrome (GBS), recurrent GBS and exacerbation of pre-existing chronic inflammatory demyelinating polyneuropathy (CIDP). We describe a case with acute-onset CIDP presenting with three relapses of demyelinating polyradiculoneuropathy, the third relapse occurring in the 8 week of illness following a previous COVID-19 infection and a recent COVID-19 vaccination with ChAdOx1 nCoV-19 and high COVID-19 antibody level. In our knowledge, this is the ever reported case of acute-onset CIDP associated with COVID-19 vaccine and high COVID-19 antibody level.
Incidence and risk factors for mortality and end-stage renal disease in people with type 2 diabetes and diabetic kidney disease: a population-based cohort study in the UK
Authors: González-Pérez Antonio , Saez Maria , Vizcaya David , Lind Marcus , Garcia Rodriguez Luis
Published: October 2021

Introduction

We aimed to determine the incidence of, and risk factors for all-cause/cardiovascular disease (CVD) mortality, and end-stage renal disease (ESRD) among people with type 2 diabetes with/without diabetic kidney disease (DKD) in the UK general population.

Research design and methods

We undertook a population-based cohort study using primary care UK electronic health records. We followed 8413 people with type 2 diabetes and DKD and a matched comparison cohort of people with type 2 diabetes without DKD. Risk factors for all-cause/CVD mortality (using both cohorts) and ESRD (DKD cohort only) were evaluated by estimating HRs with 95% CIs using Cox regression.

Results

In the DKD cohort (mean age 66.7 years, 62.4% male), incidence rates per 1000 person-years were 50.3 (all-cause mortality), 8.0 (CVD mortality) and 6.9 (ESRD). HRs (95% CIs; DKD vs comparison cohort) were 1.49 (1.35 to 1.64) for all-cause mortality and 1.60 (1.24 to 2.05) for CVD mortality. In general, higher all-cause mortality risks were seen with older age, underweight (body mass index <20 kg/m2), reduced renal function, and cardiovascular/liver disease, and lower risks were seen with being female or overweight. In the DKD cohort, higher risks of ESRD were seen with reduced renal function at baseline, high material deprivation, cancer and non-insulin glucose-lowering drugs, and a lower risk was seen with overweight (≥25 kg/m2).

Conclusions

Annually, one death will occur among every 20 people with type 2 diabetes and DKD. The identified risk factors in this study will help identify people with type 2 diabetes at most risk of death and progression of kidney disease, and help to direct effective management strategies.
Defence Medical Services’ REBOA training course
Authors: Marsden Max E R , Park C , Barratt J , Tai N , Rees P
Published: October 2021

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) enables temporary haemorrhage control and physiological stabilisation. This article describes the bespoke Defence Medical Services (DMS) training package for effectively using REBOA. The article covers how the course was designed, how the key learning objectives are taught, participant feedback and the authors’ perceptions of future training challenges and opportunities. Since the inaugural training course in April 2019, the authors have delivered six courses, training over 100 clinicians. For the first time in the UK DMS, we designed and delivered a robust specialist endovascular training programme, with demonstrable, significant increases in confidence and competence. As a result of this course, the first DMS REBOA-equipped forward surgical teams deployed in June 2019. Looking to the future, there is a requirement to develop an assessment of skill retention and the potential need for revalidation.
Application of the Ipswich Touch Test for diabetic peripheral neuropathy screening: a systematic review and meta-analysis
Authors: Zhao Nan , Xu Jingcan , Zhou Qiuhong , Li Xinyi , Chen Jiarui , Zhou Jing , Zhou Feng , Liang Jinghong
Published: October 2021

Objective

Diabetic peripheral neuropathy (DPN) is one of the most important risk factors of diabetic foot ulcers, and early screening and treatment of DPN are crucial. The Ipswich Touch Test (IPTT) is a new method for screening for DPN and, compared with traditional methods, is more simple to operate and requires no equipment. However, the screening accuracy of IPTT in patients with DPN has not been well characterised. We aim to conduct a systematic review and meta-analysis to characterise the sensitivity and specificity of IPTT compared with traditional methods and to understand the potential screening value of IPTT.

Design

Systematic review and meta-analysis.

Data sources

PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database up to 16 April 2020.

Methods

Stata V.15.1 software was used for analysis, and the screening value of IPTT in DPN was described using 10 g monofilament (10g-MF), neuropathy disability scores (NDS), Pin prick, 128 Hz tuning fork, and ankle reflex as reference standards. Sensitivity, specificity and other measures of accuracy of IPTT for screening DPN were pooled based on a quality effects model. The protocol was registered with PROSPERO (42020168420).

Results

Of the 441 records retrieved, 7 studies were evaluated for the screening value of IPTT. Five studies with 10g-MF as the reference standard were included in the meta-analysis, and the pooled sensitivity and specificity were 0.77 (95％CI 0.69–0.84) and 0.96(95％CI 0.93–0.98), respectively, and the area under curve was 0.897. Compared with vibration perception threshold, IPTT showed a sensitivity between 0.76 and 1, and a specificity between 0.90 and 0.97. Compared with NDS, IPTT showed a sensitivity between 0.53 and 1, and a specificity between 0.90 and 0.97. Compared with Pin prick, IPTT showed a sensitivity and specificity of 0.8 and 0.88, respectively. Compared with 128 Hz tuning fork, IPTT showed a sensitivity and specificity of 0.4 and 0.27, respectively. Compared with ankle reflex, IPTT had a sensitivity of 0.2 and a specificity of 0.97.

Conclusions

IPTT shows a high degree of agreement with other commonly used screening tools for DPN screening. It can be used clinically, especially in remote areas and in primary medical institutions, and by self-monitoring patients. More high-quality studies are needed to assess and promote more effective screening practices.

PROSPERO registration number

Registration Number is CRD (42020168420).
Protecting the healthcare workforce during COVID-19: a qualitative needs assessment of employee occupational health in the US national Veterans Health Administration
Authors: Brown-Johnson Cati , McCaa Matthew D , Giannitrapani Susan , Singer Sara J , Lorenz Karl A , Yano Elizabeth M , Thanassi Wendy T , DeShields Cheyenne , Giannitrapani Karleen F
Published: October 2021

Objective

Early in the COVID-19 pandemic, US Veterans Health Administration (VHA) employee occupational health (EOH) providers were tasked with assuming a central role in coordinating employee COVID-19 screening and clearance for duty, representing entirely novel EOH responsibilities. In a rapid qualitative needs assessment, we aimed to identify learnings from the field to support the vastly expanding role of EOH providers in a national healthcare system.

Methods

We employed rapid qualitative analysis of key informant interviews in a maximal variation sample on the parameters of job type, rural versus urban and provider gender. We interviewed 21 VHA EOH providers between July and December 2020. This sample represents 15 facilities from diverse regions of the USA (large, medium and small facilities in the Mid-Atlantic; medium sites in the South; large facilities in the West and Pacific Northwest).

Results

Five interdependent needs included: (1) infrastructure to support employee population management, including tools that facilitate infection control measures such as contact tracing (eg, employee-facing electronic health records and coordinated databases); (2) mechanisms for information sharing across settings (eg, VHA listserv), especially for changing policy and protocols; (3) sufficiently resourced staffing using detailing to align EOH needs with human resource capital; (4) connected and resourced local and national leaders; and (5) strategies to support healthcare worker mental health.

Our identified facilitators for EOH assuming new challenging and dynamically changing roles during COVID-19 included: (A) training or access to expertise; (B) existing mechanisms for information sharing; (C) flexible and responsive staffing; and (D) leveraging other institutional expertise not previously affiliated with EOH (eg, chaplains to support bereavement).

Conclusions

Our needs assessment highlights local and system level barriers and facilitators of EOH assuming expanded roles during COVID-19. Integrating changes both within and across systems and with alignment of human capital will enable EOH preparedness for future challenges.
Is Indonesia achieving universal health coverage? Secondary analysis of national data on insurance coverage, health spending and service availability
Authors: Pratiwi Agnes Bhakti , Setiyaningsih Hermawati , Kok Maarten Olivier , Hoekstra Trynke , Mukti Ali Ghufron , Pisani Elizabeth
Published: October 2021

Objectives

To analyse the relationship between health need, insurance coverage, health service availability, service use, insurance claims and out-of-pocket spending on health across Indonesia.

Design

Secondary analysis of nationally representative quantitative data. We merged four national data sets: the National Socioeconomic Survey 2018, National Census of Villages 2018, Population Health Development Index 2018 and National Insurance Records to end 2017. Descriptive analysis and linear regression were performed.

Setting

Indonesia has one of the world’s largest single-payer national health insurance schemes. Data are individual and district level; all are representative for each of the country’s 514 districts.

Participants

Anonymised secondary data from 1 131 825 individual records in the National Socioeconomic Survey and 83 931 village records in the village census. Aggregate data for 220 million insured citizens.

Primary outcome measures

Health service use and out-of-pocket payments, by health need, insurance status and service availability. Secondary outcome: insurance claims.

Results

Self-reported national health insurance registration (60.6%) is about 10% lower compared with the insurer’s report (71.1%). Insurance coverage is highest in poorer areas, where service provision, and thus service use and health spending, are lowest. Inpatient use is higher among the insured than the uninsured (OR 2.35, 95% CI 2.27 to 2.42), controlling for health need and access), and poorer patients are most likely to report free inpatient care (53% in wealth quintile 1 vs 41% in Q5). Insured patients spend US$ 3.14 more on hospitalisation than the uninsured (95% CI 1.98 to 4.31), but the difference disappears when controlled for wealth. Lack of services is a major constraint on service use, insurance claims and out-of-pocket spending.

Conclusions

The Indonesian public insurance system protects many inpatients, especially the poorest, from excessive spending. However, others, especially in Eastern Indonesia cannot benefit because few services are available. To achieve health equity, the Indonesian government needs to address supply side constraints and reduce structural underfunding.
Understanding inequalities in COVID-19 outcomes following hospital admission for people with intellectual disability compared to the general population: a matched cohort study in the UK
Authors: Baksh R Asaad , Pape Sarah E , Smith James , Strydom André
Published: October 2021

Objectives

This study explores the hospital journey of patients with intellectual disabilities (IDs) compared with the general population after admission for COVID-19 during the first wave of the pandemic (when demand on inpatient resources was high) to identify disparities in treatment and outcomes.

Design

Matched cohort study; an ID cohort of 506 patients were matched based on age, sex and ethnicity with a control group using a 1:3 ratio to compare outcomes from the International Severe Acute Respiratory and emerging Infections Consortium WHO Clinical Characterisation Protocol UK.

Setting

Admissions for COVID-19 from UK hospitals; data on symptoms, severity, access to interventions, complications, mortality and length of stay were extracted.

Interventions

Non-invasive respiratory support, intubation, tracheostomy, ventilation and admission to intensive care units (ICU).

Results

Subjective presenting symptoms such as loss of taste/smell were less frequently reported in ID patients, whereas indicators of more severe disease such as altered consciousness and seizures were more common. Controls had higher rates of cardiovascular risk factors, asthma, rheumatological disorder and smoking. ID patients were admitted with higher respiratory rates (median=22, range=10–48) and were more likely to require oxygen therapy (35.1% vs 28.9%). Despite this, ID patients were 37% (95% CI 13% to 57%) less likely to receive non-invasive respiratory support, 40% (95% CI 7% to 63%) less likely to receive intubation and 50% (95% CI 30% to 66%) less likely to be admitted to the ICU while in hospital. They had a 56% (95% CI 17% to 102%) increased risk of dying from COVID-19 after they were hospitalised and were dying 1.44 times faster (95% CI 1.13 to 1.84) compared with controls.

Conclusions

There have been significant disparities in healthcare between people with ID and the general population during the COVID-19 pandemic, which may have contributed to excess mortality in this group.
Surveillance of adverse drug reactions at an adverse drug reaction monitoring centre in Central India: a 7-year surveillance study
Authors: Sharma Megha , Baghel Ruchi , Thakur Sunil , Adwal Sandeep
Published: October 2021

Objectives

To analyse and present the occurrence and severity of spontaneous adverse drug reaction (ADR) reports prospectively registered at an ADR monitoring centre (AMC) in Central India.

Setting and data

The survey was conducted between 2013 and 2019 at an ADR Monitoring Centre in Central India. ADRs were recorded using the standard ‘Suspected ADR Reporting form’.

Outcome measures

The causality of the ADRs were categorised using the WHO causality assessment scale to assess the relationship between a drug and the occurrence of an ADR.

Results

Totally 1980 spontaneous ADRs were reported involving 960 patients and 1316 drugs prescriptions. The occurrence of ADRs was common among male patients (64%) and patients of age between 19 and 65 years (81%). Antimicrobials caused 29% ADRs, followed by drugs of antiretroviral therapy (19%). Zidovudine caused most ADRs (88%) followed by ethambutol and ciprofloxacin. The ADRs of skin and subcutaneous tissue disorders (28%) were most common among all system organ classes followed by gastrointestinal systems (18%). Four per cent of all reported ADRs were severe. A peak of ADR reports was attained in 2016 with 224 reports, which decreased to 127 in 2019.

Conclusion

A high number of ADRs caused by antimicrobials is an alarming situation, which adds up to antimicrobial resistance. Judicious use of antimicrobials is yet again proven as need of the hour. Under-reporting of ADRs is evident in our study and is a major factor for the delay in the withdrawal of drugs responsible for causing ADRs. Interventions in terms of training and feedback are suggested to encourage and improve ADR reporting.
Improving adherence to hepatitis B vaccine administration recommendations in two newborn nurseries
Authors: Germana Sarah , Krishnan Govind , McCulloch Matthew , Trinh Jane , Shaikh Sophie
Published: October 2021

Administration of the birth dose of hepatitis B vaccine is an important step in reducing perinatally acquired hepatitis B infection, yet the USA is below the Healthy People 2020 goal for rate of administration.

In response to updated Advisory Committee on Immunisation Practices recommendations to administer the dose within 24 hours of birth, we used quality improvement methodology to implement changes that would increase the vaccination rates of healthy newborns in our nurseries. The goal was to improve the proportion of infants who receive the hepatitis B vaccine within 24 hours of birth to >90% within a 2-year period, with a secondary goal of increasing vaccination rates prior to discharge from the nursery to >95%.

Multiple Plan–Do–Study–Act (PDSA) cycles were performed. Initial cycles focused on increasing nurse and provider awareness of the updated timing recommendations. Later cycles targeted nursing workflow to facilitate timely administration of the vaccine. We implemented changes at our university medical centre and community hospital newborn nurseries.

At the university medical centre nursery, both primary and secondary goals were met; the rate of hepatitis B vaccine administration within 24 hours increased from 81.7% to 96.2%, with vaccine administration prior to discharge increasing from 93.4% to 97.9%. In the community hospital nursery, the baseline rate of hepatitis B vaccine administration within 24 hours was 78.1%, and this increased to 85.8% with the interventions, falling short of the target of >90%. Vaccine administration prior to discharge increased from 87.2% to 92.0%, also not meeting the secondary target of 95%.

Interventions that facilitated workflow had additional benefit beyond education alone to improve timing and rates of hepatitis B vaccine administration in both a university medical centre and community hospital nursery.
Health-related physical fitness in patients with complaints of hand, wrist, forearm and elbow: an exploratory study
Authors: Berduszek Redmar J , Geerdink Henk , van der Sluis Corry K , Reneman Michiel F , Dekker Rienk
Published: October 2021

Objectives

Little is known about the physical fitness of patients with complaints of hand, wrist, forearm and/or elbow and its possible determinants. Aims were to assess health-related physical fitness (HRPF) in these patients, to compare HRPF with reference values of healthy persons, and to explore whether HRPF was correlated with symptom severity, upper limb function (ULF) and physical activity (PA).

Methods

Cardiorespiratory fitness, handgrip strength and body composition, self-reported symptom severity, ULF and PA were assessed in adult outpatients with complaints of hand, wrist, forearm and/or elbow diagnosed as CANS.

Results

Measurements were completed in 25 subjects (8 males) aged 46.1±14.5 years, of which 44% had specific CANS and 56% had non-specific CANS.

Peak oxygen consumption (VO2peak) of men was 2978±983 mL/min and of women was 1978±265 mL/min. Handgrip strength of men was 47.0±11.1 kgf and of women was 32.4±6.3 kgf. Body mass index (BMI) of men was 24.2±2.6 kg/m2and of women was 27.4±6.1 kg/m2.

VO2peak of the study sample was lower than that of healthy adults (−414±510 mL/min, p<0.001). Handgrip strength and BMI were similar to reference values.

VO2peak was correlated with PA (r=0.58, p=0.004); BMI was correlated with disability (r=0.48, p=0.022). Other correlations between HRPF and symptom severity and ULF were non-significant.

Conclusions

Patients with CANS have lower cardiorespiratory fitness, but similar handgrip strength and body composition, compared with the healthy population. Cardiorespiratory fitness was correlated with PA and BMI was correlated with disability, no other correlations were observed with symptom severity and ULF.
Predicting cardiac adverse events in patients receiving immune checkpoint inhibitors: a machine learning approach
Authors: Heilbroner Samuel Peter , Few Reed , Neilan Tomas G , Mueller Judith , Chalwa Jitesh , Charest Francois , Suryadevara Somasekhar , Kratt Christine , Gomez-Caminero Andres , Dreyfus Brian
Published: October 2021

Background

Treatment with immune checkpoint inhibitors (ICIs) has been associated with an increased rate of cardiac events. There are limited data on the risk factors that predict cardiac events in patients treated with ICIs. Therefore, we created a machine learning (ML) model to predict cardiac events in this at-risk population.

Methods

We leveraged the CancerLinQ database curated by the American Society of Clinical Oncology and applied an XGBoosted decision tree to predict cardiac events in patients taking programmed death receptor-1 (PD-1) or programmed death ligand-1 (PD-L1) therapy. All curated data from patients with non-small cell lung cancer, melanoma, and renal cell carcinoma, and who were prescribed PD-1/PD-L1 therapy between 2013 and 2019, were used for training, feature interpretation, and model performance evaluation. A total of 356 potential risk factors were included in the model, including elements of patient medical history, social history, vital signs, common laboratory tests, oncological history, medication history and PD-1/PD-L1-specific factors like PD-L1 tumor expression.

Results

Our study population consisted of 4960 patients treated with PD-1/PD-L1 therapy, of whom 418 had a cardiac event. The following were key predictors of cardiac events: increased age, corticosteroids, laboratory abnormalities and medications suggestive of a history of heart disease, the extremes of weight, a lower baseline or on-treatment percentage of lymphocytes, and a higher percentage of neutrophils. The final model predicted cardiac events with an area under the curve–receiver operating characteristic of 0.65 (95% CI 0.58 to 0.75). Using our model, we divided patients into low-risk and high-risk subgroups. At 100 days, the cumulative incidence of cardiac events was 3.3% in the low-risk group and 6.1% in the high-risk group (p<0.001).

Conclusions

ML can be used to predict cardiac events in patients taking PD-1/PD-L1 therapy. Cardiac risk was driven by immunological factors (eg, percentage of lymphocytes), oncological factors (eg, low weight), and a cardiac history.
Distinct mutational profile and immune microenvironment in microsatellite-unstable andPOLE-mutated tumors
Authors: Hwang Hee Sang , Kim Deokhoon , Choi Jene
Published: October 2021

Introduction

Mismatch repair (MMR)-deficient and DNA polymerase epsilon (POLE)-mutated tumors exhibit a high tumor mutation burden (TMB) and have been proven to be associated with good responses to immune checkpoint inhibitor treatments. However, the relationship between mutational characteristics of MMR-deficient andPOLE-mutated tumors and the spatial architecture of tumor-infiltrating lymphocytes (TILs) has not been fully evaluated.

Methods

We retrieved microsatellite instability-high (MSI-high, N=20) andPOLE-mutated (N=47) cases from the clinical next-generation sequencing cohort at Asan Medical Center. Whole-slide immunostaining for CD3, CD4, CD8, FoxP3 and PD-1 were performed with tissue samples of colorectal and gastric cancer (N=24) and the tumor-positive TIL cell densities were correlated with the tumor’s mutational features. The findings were compared with the results of similar analyses in The Cancer Genome Atlas-Colorectal Adenocarcinoma (TCGA-COADREAD) cohort (N=592).

Results

The MSI-high group showed significantly higher overall TMBs with a number of insertion/deletion (indel) mutations relative to thePOLE-mutated group (median TMB; 83.6 vs 12.5/Mb). Oncogenic/likely-oncogenicPOLEmutations were identified with ultrahypermutations (≥100 mutations/Mb) (2/47, 4.3%). ConcurrentPOLEmutations of unknown significance and MSI-high cases were identified in eight cases (8/67, 11%), and two of these colorectal cancers had multiplePOLEmutations, showing an ultramutated phenotype (378.1 and 484.4/Mb) and low indel mutation burdens with complete loss of MSH-6 or PMS-2, which was similar to the mutational profile of thePOLE-inactivated tumors. Intratumoral CD3-positive, CD4-positive, CD8-positive, FoxP3-positive and PD-1-positive TIL cell densities were more strongly correlated with the indel mutation burden than with the total TMB (correlation coefficient, 0.61–0.73 vs 0.23–0.38). In addition, PI3K/AKT/mTOR pathway mutations were commonly found in MSI-high tumors (75%) but not inPOLE-mutated tumors.

Conclusions

Indel mutation burden rather than total TMB could serve as a predictor of high TILs in both MSI-high andPOLE-mutated tumors. Multiple uncharacterized/non-pathogenicPOLEmutations occurring via MMR deficiency within MSI-high tumors may have combined pathogenic roles. A mutated PI3K/AKT/mTOR pathway may be a biomarker that can be used to stratify patients with advanced MSI-high tumors for immune therapy.
CXCR6 by increasing retention of memory CD8+ T cells in the ovarian tumor microenvironment promotes immunosurveillance and control of ovarian cancer
Authors: Muthuswamy Ravikumar , McGray AJ Robert , Battaglia Sebastiano , He Wenjun , Miliotto Anthony , Eppolito Cheryl , Matsuzaki Junko , Takemasa Tsuji , Koya Richard , Chodon Thinle , Lichty Brian D , Shrikant Protul , Odunsi Kunle
Published: October 2021

Purpose

Resident memory CD8 T cells, owing to their ability to reside and persist in peripheral tissues, impart adaptive sentinel activity and amplify local immune response, and have beneficial implications for tumor surveillance and control. The current study aimed to clarify the less known chemotactic mechanisms that govern the localization, retention, and residency of memory CD8 T cells in the ovarian tumor microenvironment.

Experimental design

RNA and protein expressions of chemokine receptors in CD8+ resident memory T cells in human ovarian tumor-infiltrating CD8+ T cells and their association with survival were analyzed. The role of CXCR6 on antitumor T cells was investigated using prophylactic vaccine models in murine ovarian cancer.

Results

Chemokine receptor profiling of CD8+CD103+ resident memory tumor-infiltrating lymphocytes in patients with ovarian cancer revealed high expression of CXCR6. Analysis of The Cancer Genome Atlas (TCGA) (ovarian cancer database revealed CXCR6 to be associated with CD103 and increased patient survival. Functional studies in mouse models of ovarian cancer revealed that CXCR6 is a marker of resident, but not circulatory, tumor-specific memory CD8+ T cells. CXCR6-deficient tumor-specific CD8+ T cells showed reduced retention in tumor tissues, leading to diminished resident memory responses and poor control of ovarian cancer.

Conclusions

CXCR6, by promoting retention in tumor tissues, serves a critical role in resident memory T cell-mediated immunosurveillance and control of ovarian cancer. Future studies warrant exploiting CXCR6 to promote resident memory responses in cancers.
Adoptive cell therapy with tumor-infiltrating lymphocytes supported by checkpoint inhibition across multiple solid cancer types
Authors: Kverneland Anders Handrup , Chamberlain Christopher Aled , Borch Troels Holz , Nielsen Morten , Mørk Sofie Kirial , Kjeldsen Julie Westerlin , Lorentzen Cathrine Lund , Jørgensen Lise Pyndt , Riis Lene Buhl , Yde Christina Westmose , Met Özcan , Donia Marco , Marie Svane Inge
Published: October 2021

Background

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has shown remarkable results in malignant melanoma (MM), while studies on the potential in other cancer diagnoses are sparse. Further, the prospect of using checkpoint inhibitors (CPIs) to support TIL production and therapy remains to be explored.

Study design

TIL-based ACT with CPIs was evaluated in a clinical phase I/II trial. Ipilimumab (3 mg/kg) was administered prior to tumor resection and nivolumab (3 mg/kg, every 2 weeks ×4) in relation to TIL infusion. Preconditioning chemotherapy was given before TIL infusion and followed by low-dose (2 10e6 international units (UI) ×1 subcutaneous for 14 days) interleukin-2 stimulation.

Results

Twenty-five patients covering 10 different cancer diagnoses were treated with in vitro expanded TILs. Expansion of TILs was successful in 97% of recruited patients. Five patients had sizeable tumor regressions of 30%–63%, including two confirmed partial responses in patients with head-and-neck cancer and cholangiocarcinoma. Safety and feasibility were comparable to MM trials of ACT with the addition of expected CPI toxicity. In an exploratory analysis, tumor mutational burden and expression of the alpha-integrin CD103 (p=0.025) were associated with increased disease control. In vitro tumor reactivity was seen in both patients with an objective response and was associated with regressions in tumor size (p=0.028).

Conclusion

High success rates of TIL expansion were demonstrated across multiple solid cancers. TIL ACTs were found feasible, independent of previous therapy. Tumor regressions after ACT combined with CPIs were demonstrated in several cancer types supported by in vitro antitumor reactivity of the TILs.

Trial registration numbers

NCT03296137, and EudraCT No. 2017-002323-25.
Grain size and organic geochemistry of recent sediments in Lingding Bay, Pearl River Delta, China: implications for sediment dispersal and depositional processes perturbed by human activities
Authors: Yuan Xiuquan , Yang Qingshu , Meadows Michael E. , Luo Xiangxin , Wang Zhanghua
Published: October 2021

Lingding Bay (LDB), on the Pearl River Delta (PRD) of southern China, is a typical example of a large river mouth that is strongly affected by anthropogenic perturbations that have changed the boundary conditions of hydro- and sediment dynamic processes. An analysis of recent sedimentary patterns can shed light on the role of anthropogenic impacts on delta evolution. In this study, we collected surficial sediments from the LDB in December 2016 (dry season) and August 2017 (flood season) to analyze their grain size and organic geochemical compositions, with the aim of investigating recent depositional patterns in the bay and evaluating human impacts. The results reveal two major mud depocenters in the northeastern and southwestern parts of the bay, which are characterized by high values of grain-size end member 1 (EM1) and increased contributions of terrestrial organic carbon in the flood season. We propose that this sedimentary pattern is a manifestation of a system regime shift due to the strengthening of the fluvial function in fluvial-tide interactions and associated changes in the suspended sediment dispersal routine. We suggest that these changes are a result of recently intensified human activities, such as coastal land reclamation and sand mining. Coarsening of the surficial sediments in the LDB in the dry season and a marked increase in the terrestrial organic contribution at the mouth of the LDB indicates the redistribution of fine-grained sediments by waves and currents and increased mud export from the LDB in response to the shallowing of the bay.
Photocatalytic degradation of Eosin B dye in aqueous solution by cadmium oxide nanoparticles
Authors: Naz Falak , Saeed Khalid
Published: October 2021

Cadmium oxide (CdO) and potassium (K) doped CdO nanoparticles (NPs) were synthesized by the chemical co-precipitation method and were used as photocatalysts for the degradation of Eosin B dye. The X-ray diffraction results presented that the crystallite size of undoped CdO and K doped CdO NPs were 43.74 and 42.31 nm, respectively. The morphological study and percent composition of synthesized undoped CdO and K doped CdO NPs was done by scanning electron microscope and energy dispersive X-ray analysis. The formation of NPs was confirmed by Fourier transform infrared spectroscopy. The precursor decomposition to CdO after annealing at ∼500 °C was studied by thermogravimetric analysis. The undoped CdO and K doped CdO nanoparticles degraded about 80% and 90% of the dye, respectively, in 140 min. The maximum degradation efficiency of the dye was achieved at a pH of 4, dye initial concentration of 15 ppm, catalyst dose of 20 mg, and a temperature of 45 °C. The degradation efficiency observed for recovered undoped CdO and recovered doped CdO nanoparticles was found to be 63% and 77%, respectively.
Predictive modeling to study lifestyle politics with Facebook likes
Authors: Praet Stiene , Van Aelst Peter , van Erkel Patrick , Van der Veeken Stephan , Martens David
Published: October 2021

“Lifestyle politics” suggests that political and ideological opinions are strongly connected to our consumption choices, music and food taste, cultural preferences, and other aspects of our daily lives. With the growing political polarization this idea has become all the more relevant to a wide range of social scientists. Empirical research in this domain, however, is confronted with an impractical challenge; this type of detailed information on people’s lifestyle is very difficult to operationalize, and extremely time consuming and costly to query in a survey. A potential valuable alternative data source to capture these values and lifestyle choices is social media data. In this study, we explore the value of Facebook “like” data to complement traditional survey data to study lifestyle politics. We collect a unique dataset of Facebook likes and survey data of more than 6500 participants in Belgium, a fragmented multi-party system. Based on both types of data, we infer the political and ideological preference of our respondents. The results indicate that non-political Facebook likes are indicative of political preference and are useful to describe voters in terms of common interests, cultural preferences, and lifestyle features. This shows that social media data can be a valuable complement to traditional survey data to study lifestyle politics.
Bottom-Up Forces in Agroecosystems and Their Potential Impact on Arthropod Pest Management
Authors: Han Peng , Lavoir Anne-Violette , Rodriguez-Saona Cesar , Desneux Nicolas
Published: October 2021

Bottom-up effects are major ecological forces in crop–arthropod pest–natural enemy multitrophic interactions. Over the past two decades, bottom-up effects have been considered key levers for optimizing integrated pest management (IPM). Irrigation, fertilization, crop resistance, habitat manipulation, organic management practices, and landscape characteristics have all been shown to trigger marked bottom-up effects and thus impact pest management. In this review, we summarize current knowledge on the role of bottom-up effects in pest management and the associated mechanisms, and discuss several key study cases showing how bottom-up effects practically promote natural pest control. Bottom-up effects on IPM also contribute to sustainable intensification of agriculture in the context of agricultural transition and climate change. Finally, we highlight new research priorities in this important area. Together with top-down forces (biological control), future advances in understanding ecological mechanisms underlying key bottom-up forces could pave the way for developing novel pest management strategies and new optimized IPM programs.
Hepatocellular Carcinoma Immunotherapy
Authors: Sperandio Rubens Copia , Pestana Roberto Carmagnani , Miyamura Beatriz Viesser , Kaseb Ahmed O.
Published: October 2021

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the third leading cause of cancer-related death worldwide. Single-agent anti-PD-1 immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in early-phase trials, a finding that was not confirmed in phase III studies. The combination of atezolizumab (an anti-PD-L1 ICI) with bevacizumab (an anti-VEGF antibody) was approved as first-line therapy in 2020, however, with significant improvement in response rate, progression-free survival, and overall survival in comparison with the previous standard of care, sorafenib. Numerous ongoing clinical trials are assessing ICIs in combination with each other or with targeted agents, and also in earlier stages with local therapies. This review summarizes the latest concepts in the use of ICIs for the management of HCC.
The Immune Response in Multiple Sclerosis
Authors: Rodríguez Murúa Sofía , Farez Mauricio F. , Quintana Francisco J.
Published: October 2021

Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative disease that affects the central nervous system (CNS). MS is characterized by immune dysregulation, which results in the infiltration of the CNS by immune cells, triggering demyelination, axonal damage, and neurodegeneration. Although the exact causes of MS are not fully understood, genetic and environmental factors are thought to control MS onset and progression. In this article, we review the main immunological mechanisms involved in MS pathogenesis.