bluuebunny/crossref_metadata_2025 huggingface dataset:
PP165 Bridging The Gap Of Health Services During The COVID-19 Pandemic Through Telemedicine
Authors: Galvan Pedro , Rivas Ronald , Recalde Luciano , Ortellado José , Arbo Carlos , Portillo Juan , Mazzoleni Juan , Hilario Enrique
Published: December 2021

Introduction

Health care for patients with chronic pathologies was scarce and limited worldwide during the COVID-19 pandemic. The challenge for clinical and biomedical engineers is to develop a bridging system to maintain the basic health services for chronic pathologies. Populations living in low-income countries did not have access to basic health services during the pandemic and depended on the scarce resources of their emergency health system. There were also equity issues between urban and rural populations. In this context, telemedicine tools should be directed toward maintaining the basic health services for patients with chronic pathologies. This study evaluated the results of a telemedicine system in remote public hospitals in Paraguay to show how health care for patients with chronic pathologies has been maintained by providing access to tertiary level diagnostic services by specialists.

Methods

This descriptive study evaluated the results of using telemedicine between 2014 and 2020 for diagnosis in remote public hospitals to bridge the gap in providing basic health services for patients with chronic pathologies during the COVID-19 pandemic.

Results

A total of 620,289 telediagnoses were performed in 67 hospitals. The 399,806 electrocardiogram diagnoses performed in 61 hospitals were normal (62%) or showed unspecified arrhythmias (13%) and sinus bradycardia (10%). The 207,597 teletomography tests performed in 12 hospitals were performed on the head because of motorcycle accidents and cerebrovascular diseases (54%), on the chest (14%), and other anatomical regions. The 12,867 electroencephalograms performed in 19 hospitals were for the antecedents of seizure (54%), evolutionary controls (14%), and headache (12%). The 19 ultrasound studies corresponded to prenatal controls.

Conclusions

Although the telemedicine tool implemented in public health to bridge the gap in basic health services for patients with chronic pathologies during the COVID-19 pandemic offered better equity in the provision of services in remote locations, a widespread use assessment should be undertaken before this tool is adopted.
PP167 Cost Effectiveness Of Universal Childhood Vaccination Against Hepatitis A
Authors: Valcarcel-Nazco Cristina , Guirado-Fuentes Carmen , García-Pérez Lidia , Linertová Renata , Mar Javier , Limia-Sánchez Aurora , Soler-Soneira Marta , Varela-Martínez Carmen , Serrano-Aguilar Pedro
Published: December 2021

Introduction

Hepatitis A (HA) is a liver disease with a low mortality rate, but it can cause debilitating symptoms and fulminant hepatitis in some cases. Its incidence is greater in geographical areas with poor sanitation and hygiene. Spain is considered a low-endemicity country, so universal childhood immunization against HA is currently not financed by the National Health System. The aim of this study was to synthesize the scientific evidence on the cost effectiveness of universal childhood vaccination against HA.

Methods

Full economic evaluations, published in the English or Spanish languages, were included if they reported outcome measures related to the prevention of HA, adverse effects, or incremental cost-effectiveness ratios (ICERs). The Medline, Embase and Cochrane Library databases were searched for articles published from the beginning of the databases to April 2018.

Results

A total of 23 economic evaluations were included: one in a country of high endemicity, nine in countries of intermediate endemicity, and 13 in countries with low endemicity. Only one Spanish study, published in 1997, was found. Studies conducted in high- and intermediate- endemicity countries concluded that a universal childhood vaccination program against HA was a cost-effective option. However, in the case of countries with low endemicity the results were heterogeneous, although most agreed that a systematic vaccination strategy would not be a cost-effective option and that the adoption of such a strategy would not be justified given the limited benefits it would offer. The results of the economic evaluations depended on parameters such as the price and duration of the vaccine effect and the program coverage.

Conclusions

In countries with low endemicity the results were heterogeneous, although most studies concluded that the implementation of a universal vaccination strategy is not justified from the point of view of cost effectiveness.
PP168 Quality-Of-Life Study For Caregivers Of People With Drug-Resistant Focal Onset Seizures
Authors: Flint India , Medjedovic Jasmina , O'Flaherty Ewa Drogon , James Samuel , Savic Natasa , Soare Alexandra , Longworth Louise
Published: December 2021

Introduction

The quality of life (QoL) of caregivers who look after individuals with drug-resistant focal-onset seizures (FOS) can be significantly affected by their caregiving responsibilities. This is widely recognized by various health technology assessment bodies, including the National Institute for Health and Care Excellence. The aim of this study was to assess the QoL and to generate health-related utility data for individuals caring for adults with drug-resistant FOS. This project will provide critical information on an often neglected and undervalued aspect of epilepsy.

Methods

An online survey including questions on sociodemographic characteristics, caregiver burden and productivity, the EQ-5D-5L, and the Care Related Quality of Life (CarerQol-7D) was administered to caregivers of individuals with drug-resistant FOS in the United Kingdom.

Results

The analysis included 86 caregivers. The majority were men aged between 25 and 34 years whose caring responsibilities ranged from 25 to 34 hours per week. In the previous 28 days, most individuals they cared for experienced four FOS, with the longest seizure-free period ranging from 6 to 15 days. The patients had previously been prescribed at least four anti-seizure medications.

The caregivers’ mean EQ-5D-5L score was 0.66 (range -0.19 to 1), whilst the mean CarerQol-7D score was 71 (range 21 to 100). The most affected dimension of the EQ-5D-5L was self-care, while the most affected dimension of the CarerQol-7D was physical functioning.

Conclusions

Caring for people with drug-resistant FOS has a negative impact on the QoL of caregivers, particularly in the domains of self-care and physical functioning.
PP205 The Use Of Real-World Evidence To Support National Institute For Health And Care Excellence Medical Technology Submissions
Authors: Gibson Scott , Saunders Sita , Blüher Maximilian , Hedblom Amanda Hansson , Torres Rafael Torrejon , Saunders Rhodri
Published: December 2021

Introduction

Although randomized controlled trials (RCTs) are recognized as providing the highest level of clinical evidence, few medical device RCTs are available due to underfunding or inherent challenges associated with trial design. This study examines the extent to which real-world evidence (RWE) supports the recommendations made by the National Institute for Health and Care Excellence Medical Technologies Evaluation Programme (MTEP).

Methods

All MTEP guidance documents published online prior to October 2020 were reviewed. The “case for adoption” recommendation, type of clinical data, and clinical critiques for each MTEP submission were extracted and categorized. RWE was defined as studies with neither blinding nor prospective selection or control of patient characteristics.

Results

Of the MTEP submissions reviewed, 34 of 45 (76%) received a positive recommendation. Independent of outcome, all submissions included RWE, but only 19 (42%) utilized RCT evidence (15 were recommended and four were not). Meta-analyses of RWE were used whenever possible. The most common clinical critiques in unsuccessful submissions were the following: (i) not generalizable to the United Kingdom National Health Service (NHS); (ii) low quality; (iii) likelihood of bias; (iv) trial design faults; (v) uncertain benefit; and (vi) evidence unrelated to scope.

Conclusions

This study suggests that while the use of RCTs has not always led to a positive recommendation, RWE can be valuable in decision-making. Evidence that is generalizable to the NHS, is related to the scope, and shows clear indication of benefit is more likely to positively influence MTEP decision-making.
PP219 Combining Healthcare Solutions For Cataract Surgery. An Incremental Benefit Analysis From The Perspective Of The Russian Healthcare System
Authors: O'Boyle Derek , Korolkov Artur , O'Boyle Derek , Poletaeva Victoriya , Hsiao Carine
Published: December 2021

Introduction

Rising health expenditures lead to increasing budgetary pressures, which often manifest in budget managers seeking more for the same resources or trying to maintain the status quo with less. Consequently, enablers that drive efficiencies throughout the entire care pathway have come under increasing focus. This is particularly true in the operating room (OR) setting where considerations around operational efficiency, clinical excellence, and patient-centered care pose challenging questions. While a comprehensive solution set should be formulated, small parts of the solution can be applied now to prime systems for easy integration into future solutions. The objective of this analysis was to estimate the impact of combining custom healthcare solutions for cataract surgery from the perspective of a Russian hospital.

Methods

A decision-analytic model was developed to assess the aggregated impact of combining the following products or services for cataract surgery: an intraocular lens delivery-system; process-redesign; a phacoemulsification machine; and a phaco tip. The model and underlying assumptions were validated by clinical experts. OR time-savings was chosen as the variable of efficiency underpinning the analysis. Inputs were estimated from the literature, expert opinion, and the local cost databases. Two scenarios were defined that reflected technologies commonly used in surgical practice. The model scenarios assumed that a hospital performs 2,000 cataract procedures per year, with 100 percent adoption and equal acquisition costs.

Results

Choosing a combination of healthcare solutions for cataract surgery was associated with an incremental benefit of RUB5,935,982 per year (EUR71,364) and generated an OR time saving of approximately 237 cataract procedures.

Conclusions

This analysis highlighted that, compared with treating technologies on an individual level, combining healthcare solutions commonly used for cataract surgery has the potential to drive efficiencies and cost savings for hospitals and to reduce surgical wait lists.
PP234 Analysis Of Discussions On Twitter On The Topic Of COVID-19 Tests: Exploring A Natural Language Processing Approach
Authors: Pandey Savitri , Marshall Christopher , Pokora Maria , Oyewole Anne , Craig Dawn
Published: December 2021

Introduction

Various strategies to suppress the Coronavirus have been adopted by governments across the world; one such strategy is diagnostic testing. The anxiety of testing on individuals is difficult to quantify. This analysis explores the use of soft intelligence from Twitter (USA, UK & India) in helping better understand this issue.

Methods

A total of 650,000 tweets were collected between September and October 2020, using Twitter API using hashtags such as ‘#oxymeter’, ‘#oximeter’, ‘#antibodytest’, ‘#infraredthermometer’, ‘#swabtest’, ‘#rapidtest’, and ‘#antigen’. We applied natural language processing (TextBlob) to assign sentiment and categorize the tweets by emotions and attitude. WordCloud was then used to identify the single topmost 500 words in the whole tweet dataset.

Results

Global analysis and pre-processing of the tweets indicate that 21 percent, seven percent and four percent of tweets originated from the USA, UK, and India respectively. The tweets from #antibody, #rapid, #antigen, and #swabtest were positive sentiments, whereas #oxymeter, #infraredthermometer were mostly neutral. The underlying emotions of the tweets were approximately 2.5 times more positive than negative. The most used words in the tweets included ‘hope’ ‘insurance’, ‘symptoms’, ‘love’, ‘painful’, ‘cough’, ‘fast test’, ‘wife’, and ‘kids’.

Conclusions

The finding suggests that it may be reasonable to infer that people are generally concerned about their personal and social wellbeing, wanting to keep themselves safe and perceive testing to deliver some component of that feeling of safety. There are several limitations to this study such as it was restricted to only three countries, and includes only English language tweets with a limited number of hashtags.
PP259 Invisible Resilience: The Value Of Medical Technology In Reducing Population And Health Systems’ Vulnerability To COVID-19.
Authors: Steuten Lotte , Zamora Bernarda , Lothgren Mickael , Bruce Andrew , Towse Adrian
Published: December 2021

Introduction

COVID-19 has exposed population and health systems’ vulnerability to a highly infectious disease. People with diabetes have a higher risk of COVID-19 hospitalization and death than those without. Medicines that control blood glucose reduce this risk. We quantified COVID-19 hospital admissions and deaths averted by diabetes medicines in the UK during the March-May 2020 wave.

Methods

We estimated COVID-19 hospital and intensive care unit (ICU) admissions averted and COVID-19 hospital deaths avoided by diabetes medicines, considering a counterfactual where those medicines were not available. We used published UK-data sources on diabetes prevalence, proportion of patients achieving diabetes control with medicines, COVID-19 infection risk, probabilities for COVID-19 hospital admission, subsequent ICU admission and hospital death. We calculated the relative risk reduction of controlled vs. uncontrolled diabetes on COVID-19 hospital or ICU admission (71% and 66%, respectively), and hospital death (38%) from the UK Open Safely data.

Results

Diabetes medicines are estimated to have averted 17,417 hospital admissions, 2,752 ICU-admissions and 438 hospital deaths due to COVID-19 compared to a counterfactual where those medicines had not been available in the UK.

Conclusions

Effective medicines to control diabetes contribute to population and health systems resilience against COVID-19. Health technology assessment and policy makers should recognize that adoption and usage of health technology reduces societies’ vulnerability to similar shocks.
PP409 Cost-Effectiveness Of Ruxolitinib For Patients With Myelofibrosis: A Review Of The Literature
Authors: Karakuleli Gizem , Barham Leela
Published: December 2021

Introduction

Myelofibrosis (MF) is a rare (annual incidence estimated to be 1/100,000 in Europe), chronic hematologic disorder associated with morbidity and mortality as well as the risk of evolution to acute myeloid leukemia. Ruxolitinib (Jakavi®, Novartis) is the first JAK 1/2 inhibitor approved by the FDA and EMA in 2011 in treating MF. Ruxolitinib is considered a high-cost and life-time treatment. UK-based estimates of the cost of treatment are in the region of GBP43,000/year/patient (in 2013). Against the background of the challenge of treatments for rare diseases reaching cost-effectiveness thresholds, this study identified, collected, and appraised the available evidence on the cost-effectiveness of ruxolitinib in the treatment of MF.

Methods

A systematic approach was taken to conducting the literature review. Databases searched included PubMed, EMBASE, MEDLINE, and the Cochrane Library based on search terms informed by PICO: myelofibrosis, ruxolitinib, best available therapy/standard of care, and cost-effectiveness/cost-utility/pharmacoeconomics. The search was limited to studies published in the English language. A narrative synthesis was used to evaluate studies and the CHEERS checklist to explore the quality of reporting of the cost-effectiveness analysis.

Results

The narrative synthesis included five studies conducted in the UK, Portugal, Chile, Canada, and Finland. All cost-effectiveness analyses used data from the same two large, randomized controlled, double-blind, phase III studies (COMFORT-I and -II). Ruxolitinib was compared to the best available therapy (BAT), including hydroxyurea, no medication, and prednisone/prednisolone. Perspectives and included costs varied among analyses. Markov models and discrete state cohort models were used to evaluate the cost-effectiveness and clinical benefit was measured in quality-adjusted life years (QALY) or life years (LY) gained.

These analyses estimated the base-case incremental cost-effectiveness ratios (ICER) per QALY of (converted into USD, if appropriate, at the historic average annual exchange rate) GBP44,905 in the UK (2013; USD 70,226), EUR40,000 in Portugal (2016; USD44,272), USD54,500 (2016), CAD61,444 in Canada (2012; USD61,474), and EUR42,367 in Finland (2015; USD42,027). Based upon the cost-effectiveness thresholds applied in each of these countries, ruxolitinib was found to be universally cost-effective, albeit with price adjustments as part of the wider pricing and reimbursement processes used in these countries.

Conclusions

Ruxolitinib was found to be cost-effective in treating MF informed by different types of models and from different perspectives; however, there was some uncertainty around available data due to limited data sources.
PP452 Impact Of Patient Access Schemes On Health Technology Assessment Agency Guidance For Rare Diseases In England and Scotland
Authors: Mark Karen , Manchanda Prachi , Rubinstein Judith , Inumerable Riza Veronica
Published: December 2021

Introduction

Patient access schemes (PAS) are agreements that may enable patients to access drugs or other treatments that may not be cost effective under normal circumstances. The aim of this study was to determine whether the use of PAS by the National Institute for Health and Care Excellence (NICE) and Scottish Medicines Consortium (SMC) for recommended drugs can lead to greater access to medications for rare diseases.

Methods

Reimbursement data for rare diseases between 2004 and 2021 from health technology assessment (HTA) agencies, namely the SMC (Scotland) and NICE (England), were included. The reviews with positive HTA decisions were considered, while those with negative decisions were excluded. Several observations were made from these data and reported.

Results

Among the total positive reviews (n = 81), 43 included PAS. The inclusion of PAS in manufacturer submissions was more frequent for NICE than for the SMC (79% and 40% percent, respectively). Most of the drugs with PAS were included in the HTA guidance from both agencies. The positive NICE reviews contingent on PAS consisted of 20 drugs. For the same set of drugs, the SMC recommended 14 with PAS and one without PAS; five drugs were not assessed. Adalimumab was recommended by NICE with a PAS (base-case incremental cost-effectiveness ratio of GBP12,336 [EUR14,256]; GBP13,676 [EUR15,804]) and by the SMC without a PAS (base-case incremental cost-effectiveness ratio of GBP22,519 [EUR26,023]). Hence, without a PAS, the drug was costlier per quality-adjusted life-year for the National Health Service (NHS) Scotland.

Conclusions

PAS submissions for rare diseases are more frequent for NICE than for the SMC. With the PAS discounts, the overall cost of the drugs is reduced, resulting in cost effectiveness. The SMC approved some drugs for which NICE required a PAS to improve the economic argument. Hence, the use of PAS for these drugs could lead to potential cost-savings to the NHS Scotland.
Towards a Capability-Oriented Eco-Social Policy: Elements of a Normative Framework
Authors: Bonvin Jean-Michel , Laruffa Francesco
Published: December 2021

In this article we explore the potential of the capability approach as a normative basis for eco-social policies. While the capability approach is often interpreted as a productivist or maximalist perspective, assuming the desirability of economic growth, we suggest another understanding, which explicitly problematises the suitability of economic growth and productive employment as means for enhancing capabilities. We argue that the capability approach allows rejecting the identification of social progress with economic growth and that it calls for democratically debating the meaning of wellbeing and quality of life. We analyse the implications of this conceptualisation for the design of welfare states.
Exposure to maternal hyperglycemia and high-fat diet consumption after weaning in rats: repercussions on periovarian adipose tissue
Authors: Saullo Carolina M. , Sinzato Yuri K. , Paula Verônyca G. , Gallego Franciane Q. , Corrente José E. , Iessi Isabela L. , Volpato Gustavo T. , Damasceno Débora C.
Published: December 2021

Clinical and epidemiological studies show that maternal hyperglycemia can change the programming of offspring leading to transgenerational effects. These changes may be related to environmental factors, such as high-fat diet (HFD) consumption, and contribute to the comorbidity onset at the adulthood of the offspring. The objective of this study was to evaluate the hyperglycemic intrauterine environment, associated or not with an HFD administered from weaning to adult life on the periovarian adipose tissue of rat offspring Maternal diabetes was chemically induced by Streptozotocin. Female offsprings were randomly distributed into four experimental groups (n = 5 animals/group): Female offspring from control or diabetic mothers and fed an HFD or standard diet. HFD was prepared with lard enrichment and given from weaning to adulthood. On day 120 of life, the rats were anesthetized and sacrificed to obtain adipose tissue samples. Then, the hyperglycemic intrauterine environment and HFD fed after weaning caused a higher body weight, total fat, and periovarian fat in adult offspring, which could compromise the future reproductive function of these females. These rats showed higher adiposity index and adipocyte area, contributing to hypertrophied adipose tissue. Therefore, maternal diabetes itself causes intergenerational changes and, in association with the HFD consumption after weaning, exacerbated the changes in the adipose tissue of adult female offspring.
Planetary‐Scale Waves Seen in Thermal Infrared Images of Venusian Cloud Top
Authors: Kajiwara Naoya , Imamura Takeshi , Taguchi Makoto , Kouyama Toru
Published: December 2021

Planetary‐scale waves are thought to play a crucial role in the maintenance of the atmospheric circulation of Venus. They have been mainly studied using ultraviolet images. In this study, cloud top temperature oscillations associated with planetary‐scale waves were extracted from thermal images taken over 142 Earth days by the Longwave Infrared Camera onboard JAXA's Akatsuki spacecraft. A spectral analysis showed that multiple planetary‐scale waves overlap. The latitudinal structures of four distinct waves with periods of 3.6, 5.0, 5.4, and 6.1 days were studied. The 3.6‐day wave is considered to be a Kelvin wave and the other waves are considered to be hemispherically symmetric Rossby waves. Although the Rossby waves have similar periods, their latitudinal structures are different. The Rossby waves are considered to originate from different sources based on a comparison with analytical solutions.
Effect of Pore‐Scale Heterogeneity on Scale‐Dependent Permeability: Pore‐Network Simulation and Finite‐Size Scaling Analysis
Authors: Ghanbarian Behzad , Esmaeilpour Misagh , Ziff Robert M. , Sahimi Muhammad
Published: December 2021

A long‐standing issue in subsurface hydrology and many other related disciplines has been the scaling problem. Although the effect of length scale has been known for years, inconsistent results have been reported in the literature. Experimental data mostly indicate that the permeability k should increase with increasing sample volume, whereas simulations and some theoretical predictions appear to imply the opposite. In this paper, we use the concept of finite‐size scaling to propose a vigorous theoretical framework for addressing the effect of length scale on the permeability. We simulate fluid flow in 12 synthetic and 4 Fontainebleau pore networks to investigate the effect of small‐scale heterogeneities, such as pore‐throat size distribution and pore connectivity. Simulations were carried out for 10 pore coordination numbers, namely, Z = 1.5, 1.65, 1.75, 2, 3, 3.25, 3.5, 4, 5, and 6. For the synthetic pore networks we find a transition in the scale dependence of the permeability, with our results indicating that the permeability increases with the scale for larger pore coordination numbers, whereas the opposite is true for smaller Z. In Fontainebleau pore networks, on the other hand, the trends are decreasing permeabilities regardless of Z. Although the plot of the permeability versus the network size for each pore network appears scattered, through finite‐size scaling analysis the data collapse onto a single quasi‐universal curve. Our results demonstrate that finite‐size scaling analysis is a powerful approach for addressing the effect of length scale on the permeability.
Lateral Flow and Contributing Area Control Vegetation Cover in a Semiarid Environment
Authors: Svoray Tal , Sela Shai , Chen Li , Assouline Shmuel
Published: December 2021

Semiarid ecosystems attract attention, because they support the life of large human populations, while functioning under growing threats of degradation due to global climate change that may lead to reduced productivity and possibly irreversible desertification. Empirical support is consequently highly sought after to validate the soil‐moisture‐biomass relationship at the local scale in these ecosystems. Combining physically based models and a database of 32 years of field and remotely sensed data, we examined the effect of soil‐moisture content (SMC) on vegetation cover and patch size distribution in the heterogenous semiarid Lehavim LTER in the Negev Desert, Israel. Results from numerical solutions of flow equations in the shallow soil layer allowed predictions of distributions of SMC as the outcome of vertical and lateral water fluxes. The association of vertical fluxes with patch size distribution and vegetation cover did not support the notion that direct rainfall is sufficient for the shrubs' survival in drought conditions. However, re‐infiltration of downslope runoff, generated in sealed bare intershrub soil area, significantly contributed to the water available to supporting shrub patches. Accordingly, our approach determines potential vegetation cover in semiarid areas, due to the dependency on contributing area and rainfall‐infiltration‐runoff processes. This underscores the fact that, additionally to infiltration from direct rainfall, run‐on contribution controls vegetation cover in semiarid environments. We therefore suggest that estimations of shrub resilience to water stress should consider scenarios involving surface sealing, rainfall duration and intensity, and contributing area size—each in accordance with the contribution of lateral flows to the water available to shrubs.
CCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression
Authors: Liao Qing , Ren Yun , Yang Yuyi , Zhu Xiaohui , Zhi Yunfei , Zhang Yujie , Chen Yi , Ding Yanqing , Zhao Liang
Published: December 2021

LIM and SH3 protein 1 (LASP1) is a metastasis-related protein reported to enhance tumor progression in colorectal cancer (CRC). However, the underlying mechanism is still elusive. The chaperonin protein containing TCP1 (CCT) is a cellular molecular chaperone complex, which is necessary for the correct folding of many proteins. It contains eight subunits, CCT1-8. CCT8 is overexpressed in many cancers, however, studies on CCT8 are limited and its role on CRC development and progression remains elusive. In this study, we confirmed that CCT8 and LASP1 can interact with each other and express positively in CRC cells. CCT8 could recover the ability of LASP1 to promote the invasion of CRC; CCT8 could significantly promote the proliferation, invasion, and metastasis of colorectal cells in vivo and in vitro. Mechanically, CCT8 inhibited the entry of WTp53 into the nucleus, and there was a negative correlation between the expression of CCT8 and the nuclear expression of WTp53 in clinical colorectal tissues. CCT8 promoted the cell cycle evolution and EMT progression of CRC by inhibiting the entry of WTp53 into the nucleus. Clinically, CCT8 was highly expressed in CRC. More importantly, the overall survival of CRC patients with high expression of CCT8 was worse than that of patients with low expression of CCT8. These findings indicate that as LASP1-modulated proteins, CCT8 plays a key role in promoting the progression of colorectal cancer, which provides a potential target for clinical intervention in patients with colorectal cancer.
Precision synthesis of reducing-end thiol-modified cellulose enabled by enzyme selection
Authors: Zhong Chao , Nidetzky Bernd
Published: December 2021

Enzyme-catalyzed iterative β-1,4-glycosylation of β-glycosides is promising for bottom-up polymerization of reducing-end-modified cello-oligosaccharide chains. Self-assembly of the chains from solution yields crystalline nanocellulose materials with properties that are tunable by the glycoside group used. Cellulose chains with a reducing-end thiol group are of interest to install a controllable pattern of site-selective modifications into the nanocellulose material. Selection of the polymerizing enzyme (cellodextrin phosphorylase; CdP) was pursued here to enhance the synthetic precision of β-1-thio-glucose conversion to generate pure “1-thio-cellulose” (≥95%) unencumbered by plain (unlabeled) cellulose resulting from enzymatic side reactions. The CdP from Clostridium stercorarium (CsCdP) was 21 times more active on β-1-thio-glucose (0.17 U/mg; 45 °C) than the CdP from Clostridium cellulosi (CcCdP), and it lacked hydrolase activity, which is substantial in CcCdP, against the α-d-glucose 1-phosphate donor substrate. The combination of these enzyme properties indicated that CsCdP is a practical catalyst for 1-thio-cellulose synthesis directly from β-1-thio-glucose (8 h; 25 mol% yield) that does not require a second enzyme (cellobiose phosphorylase), which was essential when using the less selective CcCdP. The 1-thio-cellulose chains had an average degree of polymerization of ∼10 and were assembled into highly crystalline cellulose II crystallinity material.
A crystalline radical cation derived from Thiele’s hydrocarbon with redox range beyond 1 V
Authors: Loh Ying Kai , Vasko Petra , McManus Caitilín , Heilmann Andreas , Myers William K. , Aldridge Simon
Published: December 2021

Thiele’s hydrocarbon occupies a central role as an open-shell platform for new organic materials, however little is known about its redox behaviour. While recent synthetic approaches involving symmetrical carbene substitution of the CPh2 termini yield isolable neutral/dicationic analogues, the intervening radical cations are much more difficult to isolate, due to narrow compatible redox ranges (typically < 0.25 V). Here we show that a hybrid BN/carbene approach allows access to an unsymmetrical analogue of Thiele’s hydrocarbon 1, and that this strategy confers markedly enhanced stability on the radical cation. 1•+ is stable across an exceptionally wide redox range (> 1 V), permitting its isolation in crystalline form. Further single-electron oxidation affords borenium dication 12+, thereby establishing an organoboron redox system fully characterized in all three redox states. We perceive that this strategy can be extended to other transient organic radicals to widen their redox stability window and facilitate their isolation.
MVA vector expression of SARS-CoV-2 spike protein and protection of adult Syrian hamsters against SARS-CoV-2 challenge
Authors: Meseda Clement A. , Stauft Charles B. , Selvaraj Prabhuanand , Lien Christopher Z. , Pedro Cyntia , Nuñez Ivette A. , Woerner Amy M. , Wang Tony T. , Weir Jerry P.
Published: December 2021

Numerous vaccine candidates against SARS-CoV-2, the causative agent of the COVID-19 pandemic, are under development. The majority of vaccine candidates to date are designed to induce immune responses against the viral spike (S) protein, although different forms of S antigen have been incorporated. To evaluate the yield and immunogenicity of different forms of S, we constructed modified vaccinia virus Ankara (MVA) vectors expressing full-length S (MVA-S), the RBD, and soluble S ectodomain and tested their immunogenicity in dose-ranging studies in mice. All three MVA vectors induced spike-specific immunoglobulin G after one subcutaneous immunization and serum titers were boosted following a second immunization. The MVA-S and MVA-ssM elicited the strongest neutralizing antibody responses. In assessing protective efficacy, MVA-S-immunized adult Syrian hamsters were challenged with SARS-CoV-2 (USA/WA1/2020). MVA-S-vaccinated hamsters exhibited less severe manifestations of atypical pneumocyte hyperplasia, hemorrhage, vasculitis, and especially consolidation, compared to control animals. They also displayed significant reductions in gross pathology scores and weight loss, and a moderate reduction in virus shedding was observed post challenge in nasal washes. There was evidence of reduced viral replication by in situ hybridization, although the reduction in viral RNA levels in lungs and nasal turbinates did not reach significance. Taken together, the data indicate that immunization with two doses of an MVA vector expressing SARS-CoV-2 S provides protection against a stringent SARS-CoV-2 challenge of adult Syrian hamsters, reaffirm the utility of this animal model for evaluating candidate SARS-CoV-2 vaccines, and demonstrate the value of an MVA platform in facilitating vaccine development against SARS-CoV-2.
Thermal characteristics of longitudinal fin with Fourier and non-Fourier heat transfer by Fourier sine transforms
Authors: Souayeh Basma , Abro Kashif Ali
Published: December 2021

The quest for high-performance of heat transfer components on the basis of accommodating shapes, smaller weights, lower costs and little volume has significantly diverted the industries for the enhancement of heat dissipation with variable thermal properties of fins. This manuscript proposes the fractional modeling of Fourier and non-Fourier heat transfer of longitudinal fin via non-singular fractional approach. The configuration of longitudinal fin in terms of one dimension is developed for the mathematical model of parabolic and hyperbolic heat transfer equations. By considering the Fourier and non-Fourier heat transfer from longitudinal fin, the mathematical techniques of Fourier sine and Laplace transforms have been invoked. An analytic approach is tackled for handling the governing equation through special functions for the fractionalized parabolic and hyperbolic heat transfer equations in longitudinal fin. For the sake of comparative analysis of parabolic verses hyperbolic heat conduction of fin temperature, we depicted the distinct graphical illustrations; for instance, 2-dimensional graph, bar chart, contour graphs, heat graph, 3-dimensional graphs and column graphs on for the variants of different rheological impacts of longitudinal fin.
Tuberculosis trend among native and foreign-born people over a 17 year period (2004–2020) in a large province in Northern Italy
Authors: Marchese Valentina , Rossi Luca , Formenti Beatrice , Magoni Michele , Caruana Anna , Sileo Claudio , Lanfredini Laura , Castelli Francesco , Matteelli Alberto
Published: December 2021

Tuberculosis (TB) incidence should decline by 20% in the Europe in 2015–2020, in line with End-TB milestones. We retrospectively evaluated TB notifications in the province of Brescia from 2004 to 2020. Cases were classified per patient origin and entitlement to Health Assistance for foreign born people: Italians (ITA), Foreigners permanently entitled (PEF) or Temporarily Entitled (TEF) to Health Regional Assistance. Poisson regression analysis was performed to assess associations between incidence and age, sex, continent of origin and year of notification. Overall 2279 TB cases were notified: 1290 (56.6%) in PEF, 700 (30.7%) in ITA and 289 (12.7%) in TEF. Notifications declined from 15.2/100,000 in 2004 to 6.9/100,000 in 2020 (54.6% reduction, temporary increase in 2013–2018 for TEF). Age (Incidence Risk Ratio, IRR, 1.02, 1.019–1.024 95%CI), sex (IRR 1.22, 1.12–1.34 95%CI), and continent of origin were positively associated with notifications (IRR 34.8, 30.8–39.2 95%CI for Asiatic, and IRR 20.6, 18.1–23.4 95%CI for African origin), p < 0.001. Notification decline was sharper in 2020, especially among TEF. End-TB milestone for 2020 was reached, but foreigners continue to represent a high risk group for the disease. Discontinuation of services due to the COVID-19 pandemic was associated with a sharp decrease in TB notification in 2020.
Modulation of magnetoencephalography alpha band activity by radiofrequency electromagnetic field depicted in sensor and source space
Authors: Wallace Jasmina , Yahia-Cherif Lydia , Gitton Christophe , Hugueville Laurent , Lemaréchal Jean-Didier , Selmaoui Brahim
Published: December 2021

Several studies reported changes in spontaneous electroencephalogram alpha band activity related to radiofrequency electromagnetic fields, but findings showed both an increase and a decrease of its spectral power or no effect. Here, we studied the alpha band modulation after 900 MHz mobile phone radiofrequency exposure and localized cortical regions involved in these changes, via a magnetoencephalography (MEG) protocol with healthy volunteers in a double-blind, randomized, counterbalanced crossover design. MEG was recorded during eyes open and eyes closed resting-state before and after radiofrequency exposure. Potential confounding factors, known to affect alpha band activity, were assessed as control parameters to limit bias. Entire alpha band, lower and upper alpha sub-bands MEG power spectral densities were estimated in sensor and source space. Biochemistry assays for salivary biomarkers of stress (cortisol, chromogranin-A, alpha amylase), heart rate variability analysis and high-performance liquid chromatography for salivary caffeine concentration were realized. Results in sensor and source space showed a significant modulation of MEG alpha band activity after the radiofrequency exposure, with different involved cortical regions in relation to the eyes condition, probably because of different attention level with open or closed eyes. None of the control parameters reported a statistically significant difference between experimental sessions.
Operando acoustic emission monitoring of degradation processes in lithium-ion batteries with a high-entropy oxide anode
Authors: Schweidler Simon , Dreyer Sören Lukas , Breitung Ben , Brezesinski Torsten
Published: December 2021

In recent years, high-entropy oxides are receiving increasing attention for electrochemical energy-storage applications. Among them, the rocksalt (Co0.2Cu0.2Mg0.2Ni0.2Zn0.2)O (HEO) has been shown to be a promising high-capacity anode material. Because high-entropy oxides constitute a new class of electrode materials, systematic understanding of their behavior during ion insertion and extraction is yet to be established. Here, we probe the conversion-type HEO material in lithium half-cells by acoustic emission (AE) monitoring. Especially the clustering of AE signals allows for correlations of acoustic events with various processes. The initial cycle was found to be the most acoustically active because of solid-electrolyte interphase formation and chemo-mechanical degradation. In the subsequent cycles, AE was mainly detected during delithiation, a finding we attribute to the progressive crack formation and propagation. Overall, the data confirm that the AE technology as a non-destructive operando technique holds promise for gaining insight into the degradation processes occurring in battery cells during cycling.
Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients
Authors: Loucera Carlos , Peña-Chilet María , Esteban-Medina Marina , Muñoyerro-Muñiz Dolores , Villegas Román , Lopez-Miranda Jose , Rodriguez-Baño Jesus , Túnez Isaac , Bouillon Roger , Dopazo Joaquin , Quesada Gomez Jose Manuel
Published: December 2021

COVID-19 is a major worldwide health problem because of acute respiratory distress syndrome, and mortality. Several lines of evidence have suggested a relationship between the vitamin D endocrine system and severity of COVID-19. We present a survival study on a retrospective cohort of 15,968 patients, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020. Based on a central registry of electronic health records (the Andalusian Population Health Database, BPS), prescription of vitamin D or its metabolites within 15–30 days before hospitalization were recorded. The effect of prescription of vitamin D (metabolites) for other indication previous to the hospitalization was studied with respect to patient survival. Kaplan–Meier survival curves and hazard ratios support an association between prescription of these metabolites and patient survival. Such association was stronger for calcifediol (Hazard Ratio, HR = 0.67, with 95% confidence interval, CI, of [0.50–0.91]) than for cholecalciferol (HR = 0.75, with 95% CI of [0.61–0.91]), when prescribed 15 days prior hospitalization. Although the relation is maintained, there is a general decrease of this effect when a longer period of 30 days prior hospitalization is considered (calcifediol HR = 0.73, with 95% CI [0.57–0.95] and cholecalciferol HR = 0.88, with 95% CI [0.75, 1.03]), suggesting that association was stronger when the prescription was closer to the hospitalization.
Denaturation of the SARS-CoV-2 spike protein under non-thermal microwave radiation
Authors: Afaghi Pooya , Lapolla Michael Anthony , Ghandi Khashayar
Published: December 2021

SARS-CoV-2, the virus that causes COVID-19, is still a widespread threat to society. The spike protein of this virus facilitates viral entry into the host cell. Here, the denaturation of the S1 subunit of this spike protein by 2.45 GHz electromagnetic radiation was studied quantitatively. The study only pertains to the pure electromagnetic effects by eliminating the bulk heating effect of the microwave radiation in an innovative setup that is capable of controlling the temperature of the sample at any desired intensity of the electromagnetic field. This study was performed at the internal human body temperature, 37 °C, for a relatively short amount of time under a high-power electromagnetic field. The results showed that irradiating the protein with a 700 W, 2.45 GHz electromagnetic field for 2 min can denature the protein to around 95%. In comparison, this is comparable to thermal denaturation at 75 °C for 40 min. Electromagnetic denaturation of the proteins of the virus may open doors to potential therapeutic or sanitation applications.
Stakes and expertise modulate conformity in economic choice
Authors: Greenberg Jordanne , Liljeholm Mimi
Published: December 2021

The influences of expertise and group size on an individual’s tendency to align with a majority opinion have been attributed to informational and normative conformity, respectively: Whereas the former refers to the treatment of others’ decisions as proxies for outcomes, the latter involves positive affect elicited by group membership. In this study, using a social gambling task, we pitted alignment with a high- vs. low-expertise majority against a hypothetical monetary reward, thus relating conformity to a broader literature on valuation and choice, and probed the countering influence of a high-expertise minority opinion. We found that the expertise of a countering minority group significantly modulated alignment with a low-expertise majority, but only if such alignment did not come at a cost. Conversely, participants’ knowledge of payoff probabilities predicted the degree of majority alignment only when a high-expertise majority endorsed a more costly option. Implications for the relative influences of expertise and stakes on conformity are discussed.
Characteristics and impact of aged coal ash with slag emplaced in a karst cave: the case of Divaška jama, Slovenia
Authors: Oarga-Mulec Andreea , Skok Sara , Simčič Tatjana , Mulec Janez
Published: December 2021

A mixture of coal bottom ash and slag, with a fraction of fly ash (CAFAS) from steam locomotives, was placed in the cave Divaška jama to delimit and level tourist trails. Emplacement began in 1914 and carried on for several decades. The CAFAS mixed with other cave material gradually changed its structure and appearance. Currently the concentration of some elements in the CAFAS (As, Cu, Hg, Ni, Pb, Zn), and also to a lesser extent in cave sediments (Cr, Cu, Ni), indicates a possibly harmful effect on sediment-associated biota based on ecotoxicological assays. Compared to the cave sediment, the CAFAS contains distinctly different mineral phases and presents a different source of radioactivity. Microbial metabolic activity of CAFAS is low, 0.22 μl O2/gDW h, but higher than that of cave sediment. The present environmental hazards from CAFAS are estimated to be low. Whereas the emplacement of CAFAS was seen initially a long-term solution for waste disposal and management of the cave, it turned out that CAFAS enriches the underground environment with inorganic and organic compounds and disperses pollution into the cave ecosystem. After its removal from the cave, the CAFAS should be investigated thoroughly due to its susceptibility to alteration.
Longitudinal changes in complete avascular area assessed using anterior segmental optical coherence tomography angiography in filtering trabeculectomy bleb
Authors: Kido Ai , Akagi Tadamichi , Ikeda Hanako Ohashi , Kameda Takanori , Suda Kenji , Miyake Masahiro , Hasegawa Tomoko , Numa Shogo , Tsujikawa Akitaka
Published: December 2021

Optical coherence tomography angiography (OCTA) is a new technique for non-invasive imaging of blood vessels, allowing combined evaluation of both deep and surface vessels. The purpose of this study was to evaluate the post-trabeculectomy longitudinal changes in complete avascular area (CAA) of filtering blebs using anterior segment (AS-) OCTA and their association with surgical outcomes. This study included 57 eyes of 53 patients who had undergone trabeculectomy with mitomycin C. AS-OCTA images of filtering bleb were acquired at 3 and 6 months after trabeculectomy, and at 1 month in possible cases. CAAs, regions where complete blood flow was not depicted in AS-OCTA images, were evaluated for their presence, extent, and change over time. CAAs were detected in 37 eyes (65%) and 33 eyes (58%) at 3 and 6 months postoperatively, respectively. The extent of CAAs reduced over time after surgery in most cases. No parameters related to CAAs were significantly associated with surgical success (i.e., intraocular pressure (IOP) ≤ 12 mmHg and IOP reduction > 20% without medication). In conclusion, although it is difficult to predict surgical success by CAA itself, AS-OCTA may be useful for the objective evaluation of the vascularity of filtering blebs.