bluuebunny/crossref_metadata_2025 huggingface dataset:
PD13 Methodologies In Economic Evaluations Of Biomarkers – A Systematic Review
Authors: Neeser Kurt , Koller Linnea , Mueller Elvira
Published: December 2022

Introduction

Diagnostic testing and patient monitoring are important to diagnose potential diseases and to evaluate treatment regimens. Since diagnosis and treatment monitoring have no intrinsic effects, an economic evaluation of biomarkers is inevitably linked to the resulting therapeutic interventions, which depend on both physicians’ decisions and diagnostic accuracy of the test (i.e., sensitivity, specificity). In this review we analyzed the methodology of economic studies evaluating the management of the five most relevant non-communicable diseases, that is, obesity, cancer, diabetes, cardiovascular and chronic respiratory diseases.

Methods

A systematic search in Medline and the National Health Service Economic Evaluation Database (NHS EED) covering the last ten years served to identify health economic analyses of biomarkers used in diagnosing / monitoring. Findings were reviewed with respect to analytical method, reported outcomes and comparability.

Results

The search yielded 680 abstracts in total out of which 280 full texts were reviewed and 77 sources included following predefined criteria. Most economic analyses (94%) evaluated the clinical outcome and costs of testing / monitoring in correlation to a corresponding intervention, 6 percent of the sources focused on the accuracy of the test or monitoring methods only. There were 61 studies that included an economic model; overall, 15 sources presented the outcome as cost per life year gained (CEA), 37 sources as cost per QALY gained (CUA), and 12 provided the outcome as both a CEA and CUA. In 16 analyses the outcome was presented in other economic terms as, for example, cost per additional case detected.

Conclusions

Determining the value of biomarkers requires consideration of the clinical consequences of a test result (incorrect treatment decisions, impact on morbidity, mortality, or quality of life) as well as the corresponding economic outcomes. Most of the identified studies considered at least one of these aspects. Results are presented in manifold ways but do not necessarily address decision makers’ needs. Thus, clear guidelines on economic evaluations of biomarkers are needed and should include broader health system views like affordability or the number of unnecessary interventions avoided.
PD21 Data Sources And Real-World Data On Medical Devices In The Brazilian Scenario
Authors: Teixeira Leidy Anne , Toscas Fotini
Published: December 2022

Introduction

The Brazilian government has made efforts in systems to generate data from medical devices (MD). This work explores the main systems and data sources in the perspective of contributing as a source to generate real world data (RDW).

Methods

Document review of relevant national data sources for MD. In addition, a structured search was carried out in EMBASE using key descriptors for RWD applied to the regulatory context and to the management of health technologies, without date or language restrictions.

Results

Eighteen primary federal government data sources for MD were identified. Not all sources are publicly accessible. Of the articles, the search returned 1,185 results, of which 29 titles were selected and 8 met the protocol’s objective. Included articles were from Europe, the United States and Canada. As in other countries, Brazil initially systematized DM administrative data to meet commercial and financial demands. With the evolution of health technology assessment methods, the use of RDW has become imperative to assess the value of MD to society. Common examples from these countries are implantable MD databases. Current challenges focus on data linkage and quality, in addition to standardized naming. The adoption of the Unique Device Identification (UDI) is one of the promising initiatives to facilitate traceability throughout the lifecycle proposed in the International Medical Device Regulators Forum (IMDRF) of which Brazil is a member. Among the systems, the following stand out: i) ConectSUS, which intends to provide access to health information centered on the patient, anywhere and at any time; ii) National implant registry that generates data on implanted prostheses and stents, surgical techniques used, the profile of patients and the health services involved.

Conclusions

This work showed the similarities between Brazil and other countries in the management of MD data throughout its life cycle, as well as mapped the national primary data sources for MD.
PD32 Cost-Utility Of Selective Internal Radiation Therapy Using Y-90 Resin Microspheres For Chemotherapy-Refractory Metastatic Colorectal Cancer In Brazil
Authors: Pollock Richard F , Shergill Suki , Brennan Victoria K , Agirrezabal Ion
Published: December 2022

Introduction

There were an estimated 55,102 new cases of colorectal cancer (CRC) in Brazil in 2020, comprising 9.3 percent of all newly diagnosed cancers, and making it the third most common cancer in the Brazilian population. Up to half of all patients with CRC will develop liver metastases, and the prognosis for these patients is poor. The objective of the present analysis was to evaluate the cost-utility of selective internal radiation therapy (SIRT) using Y-90 resin microspheres versus best supportive care (BSC) in patients with unresectable, liver-dominant, chemotherapy-refractory metastatic CRC (mCRC).

Methods

A three-state partitioned survival model was developed in Microsoft Excel to evaluate the cost-utility of SIRT using Y-90 resin microspheres versus BSC. Membership of the three model states of pre-progression, post-progression and death was governed by parametric models of Kaplan-Meier data from a retrospective, interventional study. Costs associated with SIRT using Y-90 resin microspheres, BSC, and adverse events were obtained from Brazilian sources and reported in 2021 United States dollars (USD). Future costs and effects were discounted at 5 percent. One-way and probabilistic sensitivity analyses (PSA) were performed. A willingness-to-pay threshold of USD 53,936 was used based on a 2017 review of Brazilian healthcare technology adoption.

Results

The base case analysis showed that Y-90 resin microspheres would result in an increase of 0.76 QALYs versus BSC, increasing quality-adjusted life expectancy from 0.67 QALYs to 1.43 QALYs. The improvement in quality-adjusted life expectancy was accompanied by an increase in costs from USD 9,884 to USD 40,399 over the model time horizon, corresponding to an increase of USD 30,515, and yielding an incremental cost-utility ratio (ICUR) of USD 40,265 per QALY gained. PSA showed there was a 90.8 percent likelihood of cost-effectiveness at USD 53,936 per QALY gained.

Conclusions

SIRT using Y-90 resin microspheres was cost-effective versus BSC in the treatment of unresectable, liver-dominant mCRC patients and should be considered for incorporation in the Brazilian Private Healthcare System.
PD34 Neuron-specific Biomarkers Associated With Neurological Manifestations In COVID-19: An Evidence Mapping Systematic Review
Authors: Domingues Karime , Cobre Alexandre , Tonin Fernanda Stumpf , Pontarolo Roberto
Published: December 2022

Introduction

We aimed to map and synthesize the available evidence on neuron-specific biomarkers related to COVID-19.

Methods

A systematic review and qualitative evidence mapping synthesis was performed (PROSPERO-CRD42021266995). Searches were conducted in PubMed and Scopus, and complemented by manual search (July 2021). We included observational studies of any design assessing neurological biomarkers in adult patients (>18 years; with or without neurological comorbidities) diagnosed with COVID-19. Methodological quality of nonrandomized studies (case-control, cohorts) was assessed using the Newcastle-Ottawa Scale.

Results

Overall, 14 studies (n=485 patients) conducted in Sweden (n=4 articles, 28.5%), Germany (n=3; 21.4%), USA (n=3; 21.4%), Canada, France, Italy and Norway (n=1 study each) were included. The most reported neurological symptoms (n=13 studies, 92.8%) were headache, confusion, general weakness, loss of smell/taste, cognitive impairments and behavioral changes. Prevalent neurological conditions included encephalopathies, neuropathies, myopathies, and delirium; most critical cases presented cerebrovascular events (n=4 studies, 28.5%). Hypertension, diabetes, obesity, dyslipidemia, and chronic lung disease were the most reported comorbidities. Eight different neuron-specific biomarkers were found in primary studies: neurofilament-light chain – NfL (n=10 studies; 71.4%), glial fibrillary acidic-protein – GFAp (n=5; 35.7%), tau protein (n=5; 35.7%), neurofilament-heavy chain – NfH, S100B protein, ubiquitin C-terminal hydrolase L1 - UCH-L1, neuron-specific enolase and beta protein-amyloid – Aβ (n=1 study each). These biomarkers were found both in cerebrospinal fluid and blood/plasma samples even without an evident cytokine storm. In patients with COVID-19, NfL and GFAp can act as sensitive indicators of neuroaxonal and astrocytic damages, respectively. Increased levels of NfL were significantly associated with severe COVID-19, unconsciousness and longer stay in the intensive care unit (p<0.05). Studies had an overall poor to moderate methodological quality.

Conclusions

We identified eight neuron-specific biomarkers that should be further studied as prognostic factors of COVID-19. These findings can also guide the development of targeted therapies against SARS-CoV-2. Additional well-designed clinical trials are needed to strengthen this evidence and help understand the mechanisms of neurological symptoms and sequelae after COVID-19 infection.
PD35 Mortality And Risk Factors Associated With Dialysis Patients With COVID-19 In A Brazilian Supplementary Health Service
Authors: de Castro Zocrato Karina , Cruvinel Horta Maria da Glória , Camelo Ricardo Mesquita , Coelho Ribeiro Geraldo Jose , Campos Nelson Otávio Beltrão , de Oliveira Douglas Ribeiro , dos Reis Daniel Pitchon , Fernandes Mariana Ribeiro , Terenzi Cunha Patrícia Liz , Annemarie Dusanek Lélia Maria de Almeida Carvalho , Biscione Fernando Martín , Kelles Silvana
Published: December 2022

Introduction

Patients with chronic kidney disease (CKD) and COVID-19 are at high risk of adverse outcomes due to the presence of comorbidities. However, it is still unclear whether dialysis therapy is associated with a worse prognosis in patients infected with SARS-CoV-2. The objectives were to assess mortality and risk factors associated with a worse prognosis of these patients (e.g., age, sex, comorbidities, Intensive Care Admission [ICU] admission, and need for invasive mechanical ventilation [IMV]).

Methods

An observational, descriptive, retrospective study was conducted in the private healthcare maintenance organization (Unimed-BH) of Belo Horizonte and 33 surrounding cities in Brazil. We used data collected from the organization’s database. We included adult inpatients with CKD on previous dialysis therapy who tested positive for COVID-19, from February 2020 to June 2021.

Results

During the period, 16182 patients were admitted to Unimed-BH with a diagnosis of COVID-19. Of these, 333 (2%) had dialysis CKD. Male patients were 180 (54%), age ranged from 22.85 to 95.75 years and the mean was 60.91 years. Of the 333 patients, 109 (32.7%) were admitted to the ICU, and 56 (16.8%) required IMV. Among the 14 comorbidities analysed, the mean number of comorbidities was 6, with 93 (27.9%) dyslipidaemia, 74 (22%) diabetic, 270 (81%) hypertensive, 25 (7.5%) asthmatic, 42 (12.6%) with chronic pulmonary disease (CPD) and 122 (36.6%) with congestive heart failure (CHF). There were 66 (19.8%) deaths, 29 (43.9%) were male, the mean age was 60.8 years, and 23 patients (34.8%) were elderly (>60 years). Among the patients who died, 55 (83.3%) were in the ICU and 46 (69.7%) on IMV. The mean number of comorbidities was 9.27 being 16 (24.2%) dyslipidaemia, 44 (66.6%) diabetic, 60 (90.9%) hypertensive, 5 (7%) asthmatic, 10 (15%) with CPD and 32 (48.5%) with CHF.

Conclusions

Dialysis patients appear more susceptible to unfavourable outcomes than the general population. Our findings are similar to those reported in the world literature which is still scarce. It is important to conduct more studies on this population.
PD38 Telehealth Use To Fight The COVID-19 Pandemic In A Brazilian Private Healthcare System
Authors: Ribeiro Geraldo Jose Coelho , Cruvinel Horta Maria da Glória , Camelo Ricardo Mesquita , Beltrão Campos Nelson Otávio , de Oliveira Douglas Ribeiro , de Almeida Carvalho Lélia Maria , de Castro Zocrato Karina , dos Reis Daniel Pitchon , Fernandes Mariana Ribeiro , Terenzi Cunha Patrícia Liz , Dusanek Annemarie , Biscione Fernando Martín , Kelles Silvana
Published: December 2022

Introduction

The outbreak of the COVID-19 pandemic generated the need to adapt patients’ access to health services, given the rapid and exponential increase in demand at all levels of care, making social distancing one of the few weapons available in this fight. In this scenario, telehealth proved to be a fundamental tool in tracking and guiding patients with suspected or confirmed disease. This work presents the demographic profile of the people attended, the most prevalent clinical situations in care and the clinical outcomes of the remote care.

Methods

This was an observational, descriptive, cross-sectional, retrospective study carried out at Unimed Belo Horizonte, a medical work cooperative, from March 2020 to May 2021. We analyzed anonymized data on remote care from electronic medical records provided by the operator, with the remote contacts of these patients being spontaneous.

Results

In the period evaluated, 380,663 remote calls were made, with a monthly average of 36,888 calls. Of these visits, 59.5% were carried out by women and 40.5% by men. There were, 13,211 (3.5%) consultations with patients aged 0 to 9 years, 19,933 (5.2%) 10 to 19 years, 319,882 (84%) in people aged 20 to 59 years, and 27,633 (7.3%) aged 60 years or older. There were 64,348 (17%) consultations in patients with confirmed COVID-19 and 40,997 (11%) with suspected COVID-19. There were 194,746 (51.2%) consultations due to respiratory complaints and 14% of consultations due to other causes, but whose initial care was due to signs and symptoms suggestive of COVID-19. Of people assisted remotely, 29,734 (7.8%) attended the emergency room within 3 days, while 38,685 (10.2%) sought the emergency room within 14 days. There were 2,846 (0.7%) consultations in the emergency room that resulted in the hospitalization of patients.

Conclusions

Telehealth proved to be resolute and an important tool for accessing health services during the pandemic.
PD44 Realistic Review: Theoretical Model For Monitoring And Evaluation (M&E) Of Health Technology Assessment Management
Authors: De Assis Patroclo Maria Aparecida , Elias Flávia
Published: December 2022

Introduction

Realistic Review (RR) is a methodology for systematic review proposed by Pawson (2002), to guide policy formulation. It is aimed at policy makers and decision makers and seeks to explain how a given intervention succeeds or fails in a certain context, allowing the identification of more suitable alternatives to solve problems. The objective of this study was to develop a theoretical model for Monitoring and Evaluation (M&E) of Health Technology Assessment (HTA) management.

Methods

The realistic review sought to identify aspects that influence HTA contributions. Studies were included if they provided a description of context and description of HTA contributions. Key purpose elements were extracted from selected studies and the contexts of HTA contributions were analyzed. The association between context and types and areas of contributions of HTA in different realities was synthesized. We analyzed thirty-one articles published in international journals in the area of health technology assessment and three articles on assessment policy in Brazil, nominated by experts.

Results

It was possible to identify situations that generate demands for HTA; favorable and unfavorable contexts and factors for contributions; main functions of networks; main products resulting from the application of evaluations; results and impact predicted by the action of the networks.

The logical model starts with conjunctural aspects that generate demands: economic, social and cultural. In a favorable context, the definition of priorities and debates in the negotiation arenas influence research and the policy formulation process. Networks identify evidence and contribute to knowledge management, generating products, results and impacts.

Conclusions

The use of the theoretical model created from the realistic review is a tool that allows the M&E of HTA management.
PD48 Does Unmet Need Influence The Scottish Medicines Consortium Health Technology Assessment Decisions For Rare Disease Conditions?
Authors: Mark Karen , Wahal Vishnu Priya
Published: December 2022

Introduction

The Scottish Medicines Consortium (SMC) defines end-of-life medicines as drugs used for treating conditions that usually lead to death within three years using currently available treatments. Orphan medicines are drugs used for the treatment of very rare conditions and ultra-orphan drugs are used for the treatment of extremely rare conditions. The objective of this study is to determine the influence of unmet need on SMC health technology assessment (HTA) decisions for rare disease conditions.

Methods

The reimbursement data between 2004 and 2021 from SMC for rare disease conditions were included. These data were categorized based on the presence of an unmet need, that is, drugs considered under the orphan or ultra-orphan process, or those that fulfilled SMC end-of-life criteria. A chi square test was conducted to determine an association between the presence of an unmet need and the HTA decision. HTAs without a decision were excluded.

Results

A total of 91 HTAs were included in the analysis of which, 57.1 percent (n = 52) were recommended, and 42.9 percent (n = 39) were not recommended. Out of the recommended reviews, 32.7 percent (n = 17) addressed an unmet need and 67.3 percent (n = 35) did not. Recommended drugs had positive clinical evidence and high cost-effectiveness or the submission of a patient access scheme while negative decisions were associated with lower or uncertain cost-effectiveness. The chi square test result showed no association between the presence of an unmet need and the HTA decision (p = 0.315).

Conclusions

Unmet need does not influence the SMC HTA decisions for rare disease conditions. Economic elements were the driving factors in the decision-making process.
PD56 Conceptual Issues In The Valuation Of Health States In Children
Authors: Shah Koonal , Lipman Stefan , McNamara Simon , Mott David , Reckers-Droog Vivian , Schneider Paul , Coates Lizzie
Published: December 2022

Introduction

Assessing the cost utility of health technologies for pediatric patients requires robust utility values for child health states, but the methods for valuing these pediatric health states are much less established than those for valuing adult health states. This is partly because the elicitation of preferences for child health states poses many normative, ethical, and practical challenges.

Methods

This presentation examines the conceptual issues in the valuation of health states in children by addressing the following questions.

(i)

Normative theories of health state values: What are we attempting to elicit?

(ii)

Sources of preferences: Whose preferences should we elicit, and from which perspective?

(iii)

Valuation methodologies: How should we elicit preferences?

(iv)

Attaching different values to child and adult health: Is a lack of consistency problematic?

To answer these questions, we used desk research (non-systematic literature reviews) and findings from a two-part workshop held in April 2021. The workshop included 25 participants with expertise in health economics, health state valuation, child health, health technology assessment (HTA) decision-making, and ethics.

Results

We identified a lack of consensus on what is being elicited for both adults and children. Many HTA agencies recommend that the public be involved in utility generation exercises, but some criteria for defining who constitutes a member of the public exclude children. Of the many candidate sample types, perspectives, and methodologies, only a few were deemed relevant, acceptable, and feasible for use in the child health context. In addition, there were diverging views on whether it is possible to compare and integrate adult and child value sets with different properties.

Conclusions

Several questions remain to be answered before the public and other stakeholders can have confidence in child health state valuation protocols. We propose a research agenda, including both empirical and conceptual work, to inform future methodological development and to help HTA agencies make recommendations about how child utility values should be generated.
Collective labour rights of police officers: Global labour constitutionalism and militaristic labour constitutionalism
Authors: Litor Lilach
Published: December 2022

Collective labour rights, including the right to organize and strike, were recognized in the principles of the International Labour Organization (ILO) as fundamental rights. Despite their importance, different countries enacted legislation that included a ban on police organization in trade unions or a ban just on police strikes. The right of police officers to organize and strike is of particular importance nowadays at a time of increased public scrutiny and large-scale protests over incidents of extra-judicial killing by police. There is a need to recognize collective rights for police officers in order to improve working conditions and organizational justice at work for them as a way of moderating officers’ perspectives of public hostility and improving their capability to carry out their duties. Another benefit of recognizing a right to organize is the union’s capacity to advance important values, including avoiding racism and violence and assuring the compliance of individual officers with the ethics and code of conduct expected from police officers. This article seeks to address the unique topic of the linkage between the collective labour rights of police officers and varieties of constitutionalism in these critical times. It introduces two potential approaches in this regard: (1) global labour constitutionalism; and (2) militaristic labour constitutionalism. The former implements international standards set by the ILO as a basis for constitutionalism while the latter emphasizes domestic issues and the need to maintain the public order and security of citizens. The article examines the possibility of applying global labour constitutionalism as a basis for recognizing collective rights for police officers.
Tomato and bell pepper tolerance to preemergence herbicides applied posttransplant in plasticulture production
Authors: Buzanini Ana C. , Boyd Nathan S.
Published: December 2022

Preemergence (PRE) herbicides are often banded over the entire top of raised beds for broadleaf and grass control in plasticulture vegetable production systems. However, broadleaf and grass weeds may emerge from the planting holes and tears in the plastic mulch. Banded application results in herbicides applied where no holes occur, and therefore, where they are not needed. Our objective is to identify herbicides that do not harm transplanted crops when directed at transplant holes after transplant (POST) with the aim to reduce off-target applications. Therefore, we evaluated tomato and pepper tolerance to PRE herbicides applied to transplant holes 2 wk after transplant and the subsequent effects on crop tolerance and weed density. Halosulfuron, S-metolachlor, metribuzin, and pendimethalin did not injure tomato transplants, reduce height, or reduce yield. Fomesafen caused some tomato injury (7%) but had no effect on other measured parameters in Trial I. All PRE herbicides injured peppers by ≥19%, although no effect on yield was observed. Overall, halosulfuron, S-metolachlor, metribuzin, and pendimethalin can be safely applied to tomato transplant holes 2 wk after transplant with no significant crop injury nor effects on final yield, but none of the evaluated herbicides are safe for use on pepper crops.
Twenty Years of NSF Funding Show Racial Disparities
Authors: Duncombe Jenessa
Published: December 2022

White principal investigators won a disproportionate share of National Science Foundation funding between 1996 and 2016, according to an analysis of public data.
A Forest, for the Trees
Authors: Micalizio Caryl-Sue
Published: December 2022

Arrays of technologies and innovative research are helping scientists better understand forests, fires, and the future of our shared landscape.
Last Tree Standing
Authors: Donovan Robin
Published: December 2022

Refugia repopulate forests after fires, but climate change is making these woodlands increasingly unpredictable.
Short‐Term and Long‐Term Variations in Seismic Velocity at Shallow Depths of the Overriding Plate West of the Japan Trench
Authors: Tonegawa T. , Takagi R. , Sawazaki K. , Shiomi K.
Published: December 2022

Long‐term and short‐term temporal variations in seismic velocity have been investigated using seismic interferometry, and significant short‐term changes are typically recognized as velocity reductions caused by large earthquakes. In this study, using a dense network of ocean bottom seismometers (Seafloor Observation Network for Earthquakes and Tsunamis along the Japan Trench: S‐net), we measured temporal variations in seismic velocity at the top of the overriding plate in the region between the Japanese Islands and the Japan Trench. We detected abrupt velocity reductions due to the nearby Mw 7‐class earthquakes in 2016 and 2021, and gradual velocity increases mainly observed near the trench. The sudden velocity reductions due to the shallow earthquake in 2016 within the overriding plate are large above the hypocenter, while those due to the three deep earthquakes in 2021 are large near the trench, although these earthquakes occurred far from the trench. The three earthquakes are located at the top of and within the subducting oceanic crust of the Pacific Plate. The spatial distributions of the velocity reductions for the four earthquakes are consistent with those of the peak ground velocities (PGVs). This indicates that for the three deep earthquakes, seismic waves trapped within the descending Pacific Plate reach to the trench, and the trapped waves induce large PGVs, and hence substantially reducing the velocity. Long‐term variations observed near the trench are possibly caused by the recovery process of coseismic velocity reductions due to large earthquakes and/or fluid migration induced by the tectonic stress field in the region.
Contrasting Annual and Summer Phosphorus Export Using a Hybrid Bayesian Watershed Model
Authors: Karimi K. , Miller J. W. , Sankarasubramanian A. , Obenour D. R.
Published: December 2022

Nutrient pollution is a widespread environmental problem that degrades water quality worldwide. Addressing this issue calls for characterizing nutrient sources and retention rates, especially in seasons when water quality problems are most severe. Hybrid (statistical‐mechanistic) watershed models have been used to quantify nutrient loading from various source categories. However, these models are generally developed for long‐term average conditions, limiting their ability to assess temporal drivers of nutrient loading. They also have not been calibrated for season‐specific estimates of loading and retention rates. To address these issues, we developed a hybrid watershed model that incorporates interannual variability in land use and precipitation as temporal drivers of phosphorus loading and transport. We calibrate the hybrid watershed model within a Bayesian hierarchical framework on both an annual and summer basis over a multi‐decadal period (1982–2017). For our study area in the North Carolina Piedmont region (USA), we find that urban lands developed before 1980 are the largest contributor of phosphorus (per unit area), especially under dry conditions. Seasonally, summer phosphorus export rates are generally found to be lower than corresponding annual rates (kg/ha/mo), while in‐stream retention is found to be elevated in summer. In addition, we find that precipitation has a substantially larger influence on phosphorus export from agricultural lands than other source types, especially in summer, and that antecedent (May) precipitation significantly influences summer phosphorus export. Overall, our approach provides a data‐driven and probabilistic line of evidence to support watershed phosphorus management across different sources and seasons.
The effect of aging on glucose metabolism improvement after Roux-en-Y gastric bypass in type 2 diabetes rats
Authors: Chen Weijie , Yin Haixin , Xiao Jianchun , Liu Wei , Qu Qiang , Gong Fengying , He Xiaodong
Published: December 2022

Background

This study aimed to investigate the effect of aging on glucose metabolism improvement after Roux-en-Y gastric bypass (RYGB) in rat models with type 2 diabetes mellitus (T2DM).

Methods

Twenty aged Goto-Kakizaki rats were randomly assigned into RYGB-A group and sham RYGB (SR-A) group, and 10 adult Goto-Kakizaki rats also accept RYGB procedures (RYGB-Y). Glucose metabolism, resting energy expenditure (REE), glucagon-like peptide-1 (GLP-1) and total bile acid level were measured.

Results

RYGB could significantly improve glucose metabolism in aged diabetic rats. The fasting blood glucose level in the RYGB-A group decreased from 15.8 ± 1.1 mmol/l before surgery to 12.3 ± 1.5 mmol/l 16 weeks after surgery (P < 0.01), and the AUCOGTT value decreased from 2603.9 ± 155.4 (mmol/l) min to 2299.9 ± 252.8 (mmol/l) min (P = 0.08). The decrease range of fasting blood glucose in the RYGB-A group was less than that in the RYGB-Y group (20.5% ± 6.5% vs. 40.6% ± 10.6%, P < 0.01), so is the decrease range of AUCOGTT value (11.6% ± 14.8% vs. 38.5% ± 8.3%, P < 0.01). Moreover, at the 16th postoperative week, the increase range of REE of the RYGB-A group was lower than that of the RYGB-Y group (15.3% ± 11.1% vs. 29.1% ± 12.1%, P = 0.04). The increased range of bile acid of the RYGB-A group was less than that of the RYGB-Y group (80.2 ± 59.3 % vs.212.3 ± 139.0 %, P < 0.01). The GLP-1 level of the RYGB-A group was less than that of the RYGB-Y group (12.8 ± 3.9 pmol/L vs. 18.7 ± 5.6 pmol/L, P = 0.02). There was no significant difference between the RYGB-A group and the RYGB-Y group in the level of the triiodothyronine level.

Conclusions

RYGB could induce a glucose metabolism improvement in aged diabetic rats, and aging might moderate the effect of RYGB.
Monitoring the 5′UTR landscape reveals isoform switches to drive translational efficiencies in cancer
Authors: Weber Ramona , Ghoshdastider Umesh , Spies Daniel , Duré Clara , Valdivia-Francia Fabiola , Forny Merima , Ormiston Mark , Renz Peter F. , Taborsky David , Yigit Merve , Bernasconi Martino , Yamahachi Homare , Sendoel Ataman
Published: December 2022

Transcriptional and translational control are key determinants of gene expression, however, to what extent these two processes can be collectively coordinated is still poorly understood. Here, we use Nanopore long-read sequencing and cap analysis of gene expression (CAGE-seq) to document the landscape of 5′ and 3′ untranslated region (UTR) isoforms and transcription start sites of epidermal stem cells, wild-type keratinocytes and squamous cell carcinomas. Focusing on squamous cell carcinomas, we show that a small cohort of genes with alternative 5′UTR isoforms exhibit overall increased translational efficiencies and are enriched in ribosomal proteins and splicing factors. By combining polysome fractionations and CAGE-seq, we further characterize two of these UTR isoform genes with identical coding sequences and demonstrate that the underlying transcription start site heterogeneity frequently results in 5′ terminal oligopyrimidine (TOP) and pyrimidine-rich translational element (PRTE) motif switches to drive mTORC1-dependent translation of the mRNA. Genome-wide, we show that highly translated squamous cell carcinoma transcripts switch towards increased use of 5′TOP and PRTE motifs, have generally shorter 5′UTRs and expose decreased RNA secondary structures. Notably, we found that the two 5′TOP motif-containing, but not the TOP-less,RPL21transcript isoforms strongly correlated with overall survival in human head and neck squamous cell carcinoma patients. Our findings warrant isoform-specific analyses in human cancer datasets and suggest that switching between 5′UTR isoforms is an elegant and simple way to alter protein synthesis rates, set their sensitivity to the mTORC1-dependent nutrient-sensing pathway and direct the translational potential of an mRNA by the precise 5′UTR sequence.
PCNA regulates primary metabolism by scaffolding metabolic enzymes
Authors: Røst Lisa M. , Ræder Synnøve B. , Olaisen Camilla , Søgaard Caroline K. , Sharma Animesh , Bruheim Per , Otterlei Marit
Published: December 2022

The essential roles of proliferating cell nuclear antigen (PCNA) as a scaffold protein in DNA replication and repair are well established, while its cytosolic roles are less explored. Two metabolic enzymes, alpha-enolase (ENO1) and 6-phosphogluconate dehydrogenase (6PGD), both contain PCNA interacting motifs. Mutation of the PCNA interacting motif APIM in ENO1 (F423A) impaired its binding to PCNA and resulted in reduced cellular levels of ENO1 protein, reduced growth rate, reduced glucose consumption, and reduced activation of AKT. Metabolome and signalome analysis reveal large consequences of impairing the direct interaction between PCNA and ENO1. Metabolites above ENO1 in glycolysis accumulated while lower glycolytic and TCA cycle metabolite pools decreased in the APIM-mutated cells; however, their overall energetic status were similar to parental cells. Treating haematological cancer cells or activated primary monocytes with a PCNA targeting peptide drug containing APIM (ATX-101) also lead to a metabolic shift characterized by reduced glycolytic rate. In addition, we show that ATX-101 treatments reduced the ENO1 - PCNA interaction, the ENO1, GAPDH and 6PGD protein levels, as well as the 6PGD activity. Here we report for the first time that PCNA acts as a scaffold for metabolic enzymes, and thereby act as a direct regulator of primary metabolism.
Real-world use of defibrotide for veno-occlusive disease/sinusoidal obstruction syndrome: the DEFIFrance Registry Study
Authors: Mohty Mohamad , Blaise Didier , Peffault de Latour Régis , Labopin Myriam , Bourhis Jean Henri , Bruno Benedicte , Ceballos Patrice , Detrait Marie , Gandemer Virginie , Huynh Anne , Izadifar-Legrand Faezeh , Jubert Charlotte , Labussière-Wallet Hélène , Lebon Delphine , Maury Sébastien , Paillard Catherine , Pochon Cécile , Renard Cecile , Rialland Fanny , Schneider Pascale , Sirvent Anne , Asubonteng Kobby , Guindeuil Gwennaëlle , Yakoub-Agha Ibrahim , Dalle Jean-Hugues
Published: December 2022

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic cell transplantation (HCT) conditioning. The DEFIFrance post-marketing registry study evaluated effectiveness and safety in patients who received defibrotide. It collected retrospective/prospective patient data from 53 French HCT centres from July 2014 to March 2020. Primary endpoints were survival and complete response (CR; total serum bilirubin <2 mg/dL, multiorgan failure resolution) at Day 100 post-HCT among patients with severe/very severe VOD/SOS. A secondary endpoint was evaluation of treatment-emergent serious adverse events (TESAEs) of interest. Of 798 patients analysed, 251 and 81 received defibrotide treatment for severe/very severe VOD/SOS and mild/moderate VOD/SOS post-HCT, respectively; 381 received defibrotide for VOD/SOS prophylaxis. In patients with severe/very severe VOD/SOS post-HCT, Kaplan–Meier–estimated CR at Day 100 was 74% (95% confidence interval [CI]: 66%, 81%). At Day 100, 137/251 (55%) were alive and in CR. Kaplan–Meier–estimated Day 100 post-HCT survival was 61% (95% CI: 55%, 67%) in patients with severe/very severe VOD/SOS. TESAEs of interest occurred in 29% of these patients; VOD/SOS-related mortality at 12 months was 15%. DEFIFrance represents the largest collection of real-world data on post-registration defibrotide use, supporting the real-world utility of defibrotide for patients with severe/very severe VOD/SOS post-HCT.
Electroreductive coupling of benzaldehyde by balancing the formation and dimerization of the ketyl intermediate
Authors: Yu Jia , Zhang Peng , Li Lulu , Li Kailang , Zhang Gong , Liu Jia , Wang Tuo , Zhao Zhi-Jian , Gong Jinlong
Published: December 2022

Electroreductive coupling of biomass-derived benzaldehyde offers a sustainable approach to producing value-added hydrobenzoin. The low efficiency of the reaction mainly ascribes to the mismatch of initial formation and subsequent dimerization of ketyl intermediates (Ph-CH = O → Ph-C·-OH → Ph-C(OH)-C(OH)-Ph). This paper describes a strategy to balance the active sites for the generation and dimerization of ketyl intermediates by constructing bimetallic Pd/Cu electrocatalysts with tunable surface coverage of Pd. A Faradaic efficiency of 63.2% and a hydrobenzoin production rate of up to 1.27 mmol mg−1h−1(0.43 mmol cm−2h−1) are achieved at −0.40 Vvs. reversible hydrogen electrode. Experimental results and theoretical calculations reveal that Pd promotes the generation of the ketyl intermediate, and Cu enhances their dimerization. Moreover, the balance between these two sites facilitates the coupling of benzaldehyde towards hydrobenzoin. This work offers a rational strategy to design efficient electrocatalysts for complex reactions through the optimization of specified active sites for different reaction steps.
Evolutionary rescue of resistant mutants is governed by a balance between radial expansion and selection in compact populations
Authors: Aif Serhii , Appold Nico , Kampman Lucas , Hallatschek Oskar , Kayser Jona
Published: December 2022

Mutation-mediated treatment resistance is one of the primary challenges for modern antibiotic and anti-cancer therapy. Yet, many resistance mutations have a substantial fitness cost and are subject to purifying selection. How emerging resistant lineages may escape purifying selection via subsequent compensatory mutations is still unclear due to the difficulty of tracking such evolutionary rescue dynamics in space and time. Here, we introduce a system of fluorescence-coupled synthetic mutations to show that the probability of evolutionary rescue, and the resulting long-term persistence of drug resistant mutant lineages, is dramatically increased in dense microbial populations. By tracking the entire evolutionary trajectory of thousands of resistant lineages in expanding yeast colonies we uncover an underlying quasi-stable equilibrium between the opposing forces of radial expansion and natural selection, a phenomenon we term inflation-selection balance. Tailored computational models and agent-based simulations corroborate the fundamental nature of the observed effects and demonstrate the potential impact on drug resistance evolution in cancer. The described phenomena should be considered when predicting multi-step evolutionary dynamics in any mechanically compact cellular population, including pathogenic microbial biofilms and solid tumors. The insights gained will be especially valuable for the quantitative understanding of response to treatment, including emerging evolution-based therapy strategies.
Accurate temperature diagnostics for matter under extreme conditions
Authors: Dornheim Tobias , Böhme Maximilian , Kraus Dominik , Döppner Tilo , Preston Thomas R. , Moldabekov Zhandos A. , Vorberger Jan
Published: December 2022

The experimental investigation of matter under extreme densities and temperatures, as in astrophysical objects and nuclear fusion applications, constitutes one of the most active frontiers at the interface of material science, plasma physics, and engineering. The central obstacle is given by the rigorous interpretation of the experimental results, as even the diagnosis of basic parameters like the temperature T is rendered difficult at these extreme conditions. Here, we present a simple, approximation-free method to extract the temperature of arbitrarily complex materials in thermal equilibrium from X-ray Thomson scattering experiments, without the need for any simulations or an explicit deconvolution. Our paradigm can be readily implemented at modern facilities and corresponding experiments will have a profound impact on our understanding of warm dense matter and beyond, and open up a variety of appealing possibilities in the context of thermonuclear fusion, laboratory astrophysics, and related disciplines.
Association of plasma cystatin C with all-cause and cause-specific mortality among middle-aged and elderly individuals: a prospective community-based cohort study
Authors: Wu Jinhua , Liang Yuemei , Chen Rong , Xu Linli , Ou Zejin , Liang Haiying , Zhao Lina
Published: December 2022

We investigated the associations of plasma cystatin C with all-cause and cause-specific mortality risk and identified potential modifying factors affecting these associations in middle-aged and elderly people (≥ 50 years). This community-based prospective cohort study included 13,913 individuals aged ≥ 50 years from the Health and Retirement Study. Cox proportional hazard models were used to estimate the associations between cystatin C concentrations and the risk of all-cause and cardiovascular and cancer mortality after adjustment for sociodemographic characteristics, lifestyle factors, self-reported medical history, and other potential confounding factors. During a total of 71,988 person-years of follow-up (median: 5.8 years; interquartile range 3.3–7.6 years), 1893 all-cause deaths were documented, including 714 cardiovascular-related and 406 cancer-related deaths. The comparisons of the groups with the highest (quartile 4) and lowest (quartile 1) cystatin C concentrations revealed that the adjusted hazard ratios and 95% confidence intervals were 1.92 (1.62–2.28) for all-cause mortality, 1.98 (1.48–2.65) for cardiovascular mortality, and 1.62 (1.13–2.32) for cancer mortality. The associations of cystatin C concentrations with all-cause, cardiovascular and cancer mortality did not differ substantially when participants were stratified by sex, age, BMI, current smoking status, current alcohol consumption, and regular exercise (all P for interactions > 0.05). Our study indicates that an elevated plasma cystatin C concentration is associated with an increased risk of all-cause, cardiovascular and cancer mortality both men and women among the middle-aged and elderly individuals.
Effect of Populus nigra spring and autumn leaves extract on Capsicum annuum infected with pepper mild mottle virus
Authors: Gharib H. A. , Mandour A. M.
Published: December 2022

Capsicum annuum is one of the main vegetable crops for the local market and exportation in Egypt. In this concern, pepper mild mottle virus (PMMoV) infection caused a significant decrease in Capsicum sp. leading to large economic losses. An isolate of PMMoV was obtained from naturally infected pepper plants, exhibiting different patterns of mottling, leaf distortion, yellowing, and stunting of leaves. The virus was identified. The molecular detection of PMMoV was done using RT-PCR with specific primers designed for coat protein genes. An RT-PCR product (474) bp of the coat protein gene of (PMMoV) was cloned. The target of the investigation was the effect of spring and autumn ethanol extracts of Populus nigra leaves on C. annuum seedling growth and infected C. annuum with (PMMoV) under greenhouse conditions. The experimental data showed that treated spring leaf extract of P. nigra enhanced infected C. annuum seedling growth parameters and fruit quality compared to uninfected seedlings. P. nigra spring leaf extract containing some allo-chemicals had a negative effect on uninfected seedlings. P. nigra autumn leaf extract significantly improved the growth and fruit quality of infected C. annuum seedlings compared to the control.
Preparation and characterization of carex meyeriana Kunthcellulose nanofibers by electrospinning
Authors: Sun Ying , Yu Yang , Li Duanxin , Kong Weishuai , Yang Feng
Published: December 2022

The cellulose of carex meyeriana kunth (CMKC) was used as raw material, and the spinning solution was prepared by combining with polyacrylonitrile (PAN). The nano-cellulose fiber of carex meyeriana kunth (CMKN) was prepared by electrospinning. Used to remove methylene blue dye (MB) in aqueous solution. In the electrospinning experiment, the addition of CMKC was in the range of 5% ~ 25%, the feed rate of spinning parameters was set in the range of 0.2 ~ 1.0 mL/h, the distance from the needle tip to the collecting plate was in the range of 10 ~ 25 cm, and the voltage was changed in the range of 15 ~ 25 kV. The obtained CMKN was characterized by scanning electron microscope, X-ray diffraction (XRD) and Fourier transform infrared spectroscopy. The MB removal rate was evaluated in the dye removal experiment, and the effects of CMKN on MB removal rate under the factors of CMKC dosage, temperature, shock time and MB initial concentration were discussed. The optimum process conditions were determined by response surface methodology. The results show that the prepared fibers are superfine fibers with nanometer diameter, and the spun nanofibers have smooth surface, high overall orientation and strong uniformity. The adsorption kinetics of prepared CMKN accords with quasi-second order model, and the adsorption isotherm accords with Langmuir model. The maximum dye removal rate of CMKN is 63.24%.
Judgment of duration and passage of time in prospective and retrospective conditions and its predictors for short and long durations
Authors: Martinelli Natalia , Droit-Volet Sylvie
Published: December 2022

The study investigated participants' verbal duration judgment and judgment of passage of time (PoT) when presented with an image for a few seconds (20 to 45 s) or minutes (80 to 180 s) with prospective and retrospective temporal judgment instruction, with their level of attention devoted to time tested. Their self-reported levels of emotion and attention were also assessed, as well as their individual impulsivity traits. Structural equation analyses showed that the best predictor of PoT judgment was emotion (boredom) regardless of duration range. For duration judgment, the best predictor for short durations was attention-related factors. However, for long durations, these factors ceased to be significant and were replaced by emotion, in the same way as for the PoT judgment. Indeed, these analyses suggested that duration judgment and PoT judgment were related for long durations of more than one minute, whereas they were not related for short durations of a few seconds.