bluuebunny/crossref_metadata_2025 huggingface dataset:
PD40 Antigen Diagnostic Tests With Self-Collection Of Biological Material For The Diagnosis Of COVID-19
Authors: Ramos Maira , Camargo Erika , Maierovitch Claudio , Elias Flávia
Published: December 2022

Introduction

The self-test for COVID-19 has been a widely used strategy in some countries, especially in the context of back to face-to-face work and educational activities. However, it is necessary to discuss the accuracy of antigen tests for the diagnosis of COVID-19.

Methods

A systematic review was carried out. The strategy was defined by the researchers using the terms “Covid-19” and “Self-testing” and their respective synonyms, including studies with data collection from 01/01/2021. Searches were carried out on October 20, 2021, in several databases.

Results

A total of 504 studies were identified, four of which were included in this review: two self-tests of nasopharyngeal collection antigen compared to reverse transcriptase polymerase chain reaction (RT-PCR); a supervised and self-collected anterior nasal smear self-test; and a study that evaluated the performance of six self-collected rapid antigen tests against quantitative RT-PCR (gargle, sputum, and spit). Saliva self-tests were found to have low sensitivity (<45%), while anterior nasal or nasopharyngeal swab self-tests had greater than 80 percent sensitivity. In all self-tests, the specificity was less than 85 percent. The diagnostic accuracy of self-tests for the different SARS-CoV-2 variants was not identified.

Conclusions

The use of self-tests as a screening strategy is recommended, being a strategy with a significant impact on the surveillance and control of SARS-CoV-2 transmission. Further studies are needed to assess: (i) accuracy considering the concern variants, (ii) safety of tests with self-collection of biological material, and (iii) disposal of biological waste.
PD41 Role Of Artificial Intelligence In Improving Access To COVID-19 Diagnosis During Pandemic
Authors: Galvan Pedro , Fusill Jose , Gonzalez Felipe , Rivas Ronald , Grossling Benicio , Ortellado Jose , Portillo Juan , Borba Julio , Hilario Enrique
Published: December 2022

Introduction

The evolution of advances in informatics, technology in medicine, and artificial intelligence (AI) offers opportunities to enhance health care during the coronavirus disease 2019 (COVID-19) pandemic. The challenge for biomedical engineers is to implement these developments in clinical practice to improve global health. Populations living in low-income countries do not have access to specialist care and quality diagnostic services for COVID-19. Therefore, an AI system based on a telemedicine platform for diagnosing COVID-19 could help mitigate the lack of highly trained radiologists at regional hospitals and serve as a triage system for rationalizing the use of reverse transcription polymerase chain reaction (RT-PCR) testing and other health resources in low-income countries. Thus, the utility of an AI system for diagnosing COVID-19 in Paraguay was investigated.

Methods

This is a descriptive multicenter observational feasibility study of an AI tool for the rapid detection of COVID-19 in chest computed tomography (CT) images of patients with respiratory difficulties who attended public hospitals across the country.

Results

Between March 2020 and August 2021, 3,514 rapid diagnostic tests were carried out on patients with respiratory disorders to rule out COVID-19 in 14 hospitals nationwide. The average age of the patients was 48.6 years (52.8% were men); the most common age ranges were 27 to 59 years, followed by older than 60 years and 19 to 26 years. The most frequent findings on the CT images were severe pneumonia, bilateral pneumonia with pleural effusion, bilateral pulmonary emphysema, diffuse ground glass opacity, hemidiaphragmatic paresis, calcified granuloma in the lower right lobe, bilateral pleural effusion, sequelae of tuberculosis, bilateral emphysema, and fibrotic changes. Overall, there was 93 percent agreement and 7 percent discordance between the AI system and the RT-PCR test results. Compared with RT-PCR testing, the AI system had a sensitivity of 93 percent and a specificity of 80 percent.

Conclusions

Paraguay has an AI-based telemedicine screening system for the rapid detection of COVID-19 that uses chest CT images of patients with respiratory conditions.
PD42 Diagnosis Of Chronic Diseases During The COVID-19 Pandemic Through Telemedicine
Authors: Galvan Pedro , Rivas Ronald , Grossling Benicio , Ortellado José , Arbo Carlos , Portillo Juan , Borba Julio , Hilario Enrique
Published: December 2022

Introduction

The diagnosis and management of chronic diseases during the coronavirus disease 2019 (COVID-19) pandemic was one of the biggest challenges facing healthcare systems globally, especially in low-income countries. Since basic health care for chronic diseases can overwhelm the capacity of conventional face-to-face healthcare services, there is growing interest in using information and communication technology and telemedicine to improve access to medical services that are often not consistently available in rural communities. In this context, telemedicine tools should be directed toward maintaining basic health services for patients with chronic conditions in rural and underserved hospitals. This study evaluated a telemedicine system in remote public hospitals in Paraguay to demonstrate how telemedicine improved access to tertiary level diagnostic services for patients with chronic conditions.

Methods

This descriptive study evaluated the use of telemedicine for diagnosing patients in remote public hospitals to improve provision of basic health services to patients with chronic disease during the COVID-19 pandemic. The type and frequency of diagnostic studies performed were determined.

Results

During the study 677,023 telediagnoses were performed in 67 hospitals. The 435,568 electrocardiograms performed in 61 hospitals indicated normal physiology (60.1%), unspecified arrhythmias (10.5%), and sinus bradycardia (8.4%). The 227,360 teletomography tests performed in 12 hospitals were undertaken on the head (52.4%) because of trauma (motorcycle accidents) and cerebrovascular diseases, chest (15.8 %), and other anatomical regions. The 14,076 electroencephalograms performed in 19 hospitals were undertaken for antecedents of seizure (53.3%), disease progression controls (14.0%), and headache (12.5%). Nineteen prenatal ultrasound scans were conducted.

Conclusions

Although the results are promising for using telemedicine to bridge gaps and improve equity in the provision of basic health services for patients with chronic diseases in remote locations during the COVID-19 pandemic, a widespread use assessment should be undertaken before this tool is adopted.
PD47 Associations Of Orphan Designation And Other Drug Development-Related Factors On Rollout Times And Health-Technology-Assessment Recommendations Of New-Active-Substances
Authors: Sola-Barrado Belen , Wang Tina , McAuslane Neil
Published: December 2022

Introduction

The orphan designation has been used by the European Medicines Agency to incentivize the development of drugs treating rare diseases with high-unmet medical needs by supporting their development process and economic returns. This study evaluated the impact of the regulatory orphan designation and other drug development-related factors on the rollout times and Health-Technology-Assessment (HTA) recommendations of new active substances (NASs).

Methods

A total of 656 HTA appraisals from 6 European countries were collected for NASs that received regulatory approval between 2012 and 2020. Multivariable logistic (positive and positive with restrictions vs. negative HTA recommendation as dependent variable) and linear regression (rollout time as dependent variable) models examined associations with regulatory orphan designation, expedited process, product type (biotechnological vs chemical), and jurisdiction (France, England, Germany, Poland, Scotland and Sweden). Rollout time was defined as months elapsed from regulatory submission to HTA recommendation (mean± standard deviation).

Results

Multivariable logistic regression analysis identified disparities in HTA recommendations between countries. Every month increase in rollout time conferred a 3 percent reduction in the odds of a positive recommendation (p<0.001). Review and product type did not show associations with HTA recommendation. Interestingly, orphan products showed a 99% increase in the odds of obtaining a positive HTA recommendation compared to non-orphan (p-value=0.003). We found 244 appraisals (37%) assessing an orphan product, of which 202 (83%) received a positive HTA recommendation.

Multivariable linear regression analysis indicated that orphan products presented a 4.4-month rise in rollout time when compared to non-orphan products (p<0.001). The mean rollout time in months for orphan products were 25±12 in France, 30±15 in England, 21±9.1 in Germany, 37±16 in Poland, 25±12 in Scotland and 27±14 in Sweden.

Conclusions

Orphan designated products showed greater odds of receiving a positive HTA recommendation compared with non-orphan. A more detailed review of orphan products could result in their longer rollout time compared with non-orphan counterparts. Considerable differences were found between HTA recommendations and rollout times between jurisdictions.
PD49 Burden And Cost Of Anterior Cruciate Ligament Reconstruction And Reimbursement Of Its Treatment In Indonesia: An Observational Study
Authors: Deviandri Romy , van der Veen Hugo C , Lubis Andri MT , van den Akker-Scheek Inge , Postma Maarten
Published: December 2022

Introduction

The number of anterior cruciate ligament reconstruction (ACLR) procedures is increasing. However, the likelihood of not allocating sufficient funds for the ACLR procedure in a developing country, especially in Indonesia, is high. This study aimed to analyze costs for ACLR procedures in Indonesia’s resource-limited context, determine the burden of ACLR, and propose national prices for ACLR reimbursement.

Methods

A retrospective observational study was conducted on the cost of ACLR from a payer perspective using inpatient billing records from 1 January 2019 to 31 December 2019 from four hospitals. The national burden of ACLR was calculated and national prices for reimbursement were developed.

Results

Of the 80 ACLRs performed, 53 (66%) were isolated ACLRs and 27 (34%) were combined with meniscus treatment. The mean hospital costs incurred per ACLR procedure were USD 2,853 (IDR 40.4 million), which was mainly attributed to the orthopedic implants (USD 1,387; IDR 19.6 million). The costs of ACLR with combined meniscus treatment were estimated to be 35 percent higher than for isolated ACLR. The national burden of ACLR revealed a total budget of USD 367.4 million (IDR 5.2 trillion) per 100,000 patients for ACLR with additional meniscus treatment and USD 271.3 million (IDR 3.8 trillion) per 100,000 patients for the isolated ACLR procedure.

Conclusions

ACLR procedures in Indonesia are underbudgeted. Adjustment of reimbursement prices for ACLR procedures is needed to facilitate access for the Indonesian people. This study showed varying cost estimates for ACLR in Indonesia, necessitating a new reimbursement system that takes various clinical and patient factors into account.
PD52 The Role Of Public Consultation In CONITEC Recommendations Between 2012 And 2020: An Introductory Analysis
Authors: Souza Andrea Brigida , Portugal Clarice , Prates Adriana , Almeida Andrija , de Pina Viana Bruna Cabral , Losco Luiza , Canuto Vania
Published: December 2022

Introduction

Public consultation is a strategy for patient and public involvement (PPI) assured by the National Committee for Health Technology Incorporation in Brazilian Public Health System (CONITEC)´s normative framework. It aims to obtain society’s views on the matters under evaluation. It is made available after CONITEC issues an initial recommendation, which will be reviewed in light of society contributions. This paper examines the cases where the final recommendations differed from the initial ones in technology assessments carried out between 2012 and 2020, taking into account the arguments used by the CONITEC Plenary to support the modification.

Methods

From a total of 361 public consultations referring to the assessment of health technologies carried out by CONITEC between 2012 and 2020, 40 final reports of health technology assessment (HTA) processes that had changes from the initial to the final recommendation were examined. Then, analytical categories were built so that justifications for the change were investigated and the interpretations produced. The empirical approach excluded public consultations regarding clinical protocols and therapeutic guidelines.

Results

It was observed that, in 39 cases, the change occurred from an unfavorable position to a favorable position for the technology incorporation. The main reasons for changing the plenary’s decision were proposals to renegotiate the prices of technologies (that generate changes in the results of economic evaluation and budget impact analysis), the receipt of new evidence and experience, and opinion arguments sent mainly by health professionals.

Conclusions

The analyzed data has shown that the changes in recommendations are mostly based on the content of contributions which led to changes in the assessment of clinical evidence, economic evaluation and budget impact. Thus, it appears that public consultation has been consolidated as a relevant instrument to inform the deliberative process in HTA in Brazilian Public Health System.
PD53 Improving Patient Involvement In The National Institute For Health And Care Excellence’s Appeals Process
Authors: Livingstone Heidi , Pitan Maria
Published: December 2022

Introduction

Involving patients in the health technology assessment (HTA) lifecycle is a core principle at the National Institute for Health and Care Excellence (NICE) that helps build public confidence in healthcare decision-making. The last stage in this lifecycle is an appeal whereby stakeholders, including patient organizations, can appeal against the HTA committee’s decision based on two specific grounds: (i) the committee has failed to act fairly or NICE has exceeded its powers; and (ii) the recommendation is unreasonable considering the evidence submitted to NICE. Improving patient involvement in the appeals process was identified as a key area from consultative work undertaken with patient organizations in 2019.

Methods

In September 2020, surveys were sent to patient organizations for their feedback. The organizations received a survey tailored to their circumstances in relation to the following four outcomes.

(i)

An appeal was lodged that: (a) resulted in an appeal hearing; or (b) did not result in an appeal hearing.

(ii)

An appeal was not lodged but the organization had received: (a) negative guidance; or (b) ‘optimized’ guidance.

Results

Sixteen responses were received across the four surveys. The key findings in priority order were as follows.

(i)

The legalist nature of appeal hearings is off-putting.

(ii)

The online appeals guide and template letter are not easy to use.

(iii)

Organizations would like more information on appeal hearings and timelines.

(iv)

Organizations would like patient-friendly materials and training on par with the support they receive for other HTA participation.

Conclusions

As a result of these findings, we are iteratively developing materials to support patient organizations, including:

•

a glossary;

•

a redesigned appeals web page with clearer timelines and a template letter;

•

a ‘Frequently Asked Questions’ document specifically for patient organizations; and

•

a video podcast from a lay appeals panel Chair explaining appeals in a patient-friendly way.

We are also including a section on appeals in our introductory training for all patient organizations participating in medicines HTAs.
PD55 Evidence-Based Practices To Support Well-Being And School Success Of Children And Youth In Out-Of-Home Care
Authors: Goulet Julie , Maltais Christine , Noël Véronique , Archambault Isabelle
Published: December 2022

Introduction

Children and youth in out-of-home care face many challenges regarding their development and general well-being. It is necessary to put in place best practices to support them where they are most vulnerable. Providing recommendations to health and social services for best practices regarding social and academic success interventions, this study puts forward a synthesis method that combines empirical data and the expertise of key practitioners in the context of Quebec social services.

Methods

A systematic review was first undertaken to identify the most effective interventions. Included studies (n = 31) were analyzed according to their methodological quality, collaboration processes, and type of care (foster home vs. residential care). To ensure the applicability of the recommendations made in the context of Quebec social services, contextual data, and clinical expertise were collected. Contextual data was gathered through local research reports, administrative data, and government documents. The expertise of multiple stakeholders was obtained in follow-up committees and semi-structured interviews (n = 4). In addition, to ensure their relevance and scope, recommended guidelines were debated in a deliberation committee.

Results

The analysis between expert, contextual and empirical data led to several recommended evidence-based practices. In accordance with expert opinions, experimental and quasi-experimental studies show that various types of collaboration are beneficial for children and youth in out-of-home care. Notably, intersectoral collaborations were warranted in more complex situations (i.e., youth in residential centers), while partnership agreement was sufficient in less complex situations (i.e., children in foster homes). However, even if effective, some interventions are difficult to apply in real life and certain considerations must be taken into account (e.g. confidentiality issues, availability of resources).

Conclusions

Utilizing three sets of data, guidelines have been proposed to help health and social services to identify best practices and promote the academic development of out-of-home care children and youth.
PD58 Implementation And Assessment Of A Lung Cancer Screening Pilot Project In Québec Through Multi-Stakeholder Collaboration
Authors: Boily Gino , Bouchard Nicole , Boulanger Jim , Brie Marie-Hélène , Ezer Nicole , Guédon Aude-Christine , Hindié Valérie , Jehanno Cédric , Lehuédé Camille , Liberman Moishe , Lizotte Hélène , Massougbodji José , Nshimyumukiza Léon , Pelletier Andréa , Théberge Isabelle , Martel Simon , Truchon Catherine
Published: December 2022

Introduction

In 2019, the Québec provincial health technology assessment body (INESSS) recommended that lung cancer screening with low-dose computed tomography (LDCT) be accessible in Québec only within the context of an evaluation in the ‘real-world’ care setting. Based on this recommendation, the ministry of health (MSSS) decided, in 2020, to implement a screening pilot project and to conduct a formal evaluation, partnering with a clinical leader (principal investigator), participating hospitals, the provincial public health agency (INSPQ) and INESSS. The goal of this evaluation is to facilitate decision-making regarding the implementation of a province-wide screening program.

Methods

To support the implementation of the pilot project, algorithms and recommendations were developed to guide management of screening program participants. This material, based on Lung-RADS (Lung Computed Tomography Screening Reporting and Data System of the American College of Radiology), was developed by reviewing the literature and by consulting clinical experts. The evaluation plan proposes various indicators, focusing on six main topics: (i) costs, (ii) screening and investigation processes, (iii) clinical effectiveness and other effects on health, (iv) effects on smoking cessation, (v) organizational impact and (vi) implementation issues.

Results

INESSS has developed 12 algorithms and close to 50 recommendations for lung cancer screening and investigation, a tool for assessing lung cancer risk and a benefits/risks table. For the evaluation of the pilot project, MSSS, INSPQ and INESSS developed more than 100 indicators; short-term indicators are currently being measured and others will follow in the longer term. Since starting in June 2021, the pilot project is progressing well (as of November 28, 2021): 2,365 people have been referred, 1,272 were eligible for screening, 678 have had their first LDCT and 19 were Lung-RADS 4B or 4X. Results on indicators will help the ministry decide on the feasibility of scaling up screening to the provincial level and will highlight aspects to be improved.

Conclusions

This project shows how health technology assessment products can elicit changes in the health system, and how multi-stakeholder collaboration can actively support practice implementation and inform decision-making.
PD60 What Are The Opportunities And Challenges To Implementing Value Based Healthcare Pilots In The Brazilian Private Healthcare System?
Authors: Bernz Iara Muller , Pedro Gabriel Ogata , Tanaka Marcos , Tanaka Sandra , Nita Marcelo Eidi
Published: December 2022

Introduction

The Brazilian National Agency for private healthcare system (ANS) regulates the private healthcare system in Brazil. ANS, since 2019, has been running the pilot value-based new payment models project. In total, 13 projects were selected by ANS. This investigation aims to identify opportunities and challenges to implement value based healthcare (VBHC) in Brazil.

Methods

We interviewed managers participating in the ANS’ Value-Based Payment Models. Data were collected through semi-structured interviews during 2021. Twelve managers were invited to participate in the interview and eight accepted the invitation. The key questions were: “what are the main factors that facilitate – or limit - the transition from the fee for service model to a value-based model in the private healthcare system? And “will the payment models be scalable?” For data analysis, Bardin’s content analysis was chosen. Data validation was performed using the debriefings technique.

Results

The interviews identified two key facilitating factors: people (identified by 50% of respondents) and processes (identified by 50% of respondents). Reponses relating to people nominated the need for professionals with VBHC knowledge (33%), support of senior management (25%), support from the provider (25%) and care team (17%). Reponses relating to processes nominated the need for partnership (58%), health-driven management (25%) and results (17%). We also identified that limiting factors (49%) were: providers (39%), in details: non-support from the provider, (56%), fear of financial loss (22%) and provider only wanting profit (22%); information system (30%), with data management; culture (17%), current versus innovative models; and peoples (13%), knowledge. More than 90 percent found it to be scalable, particularly, in vertical health plans (38%), large operators (38%); and provide diagnostic services (13%). We found that non-scalable situations are those where fee for service is hegemonic in terms of payments.

Conclusions

Our study found that knowledge and culture management positively impacts the projects. Service providers can be limiting when they are exclusively focused on economic perspectives. The new payment model is considered scalable.
PerformingOt(h)ello: Verdi, Salvini and the Stage Manual
Authors: De Francisci Enza
Published: December 2022

This article retraces Giuseppe Verdi'sOtello(1887) to the great Italianmattatori(star actors), particularly Tommaso Salvini (1829–1915), whose ground-breaking performances of the Moor of Venice, in a translation by Giulio Carcano, coincided with the time when Verdi and his librettist, Arrigo Boito, were collaborating on theirOtello. Thegrandi attorienjoyed a reputation for realistic immediacy and impulsiveness readily associated with cultural stereotypes about Italy's perceived ‘otherness’. In the ethnographic context of nineteenth-century Italy, it is argued here that the actors’ interpretation of Shakespeare's Moor not only synthesised the multilateral cultural threads of the Jacobean Othello, but also partnered this racial alterity with a new dramatic language, which went on to influence Verdi's opera and prompt book, and, ultimately, to perpetuate an exoticised ‘brand’ of Italian artistic culture on stage at a time when Italy was fashioning its own national identity.
Development of the Residual Lesion Score for congenital heart surgery: the RAND Delphi methodology
Authors: Nathan Meena , Newburger Jane W. , Bell Margaret , Tang Alexander , Gongwer Russell , Dunbar-Masterson Carolyn , Atz Andrew M. , Bacha Emile , Colan Steven , Gaynor J. William , Kanter Kirk , Levine Jami C. , Ohye Richard , Pizarro Christian , Schwartz Steven , Shirali Girish , Tani Lloyd , Tweddell James , Gurvitz Michelle ,   for the Pediatric Heart Network Investigators
Published: December 2022

Background and Objective:

The Residual Lesion Score is a novel tool for assessing the achievement of surgical objectives in congenital heart surgery based on widely available clinical and echocardiographic characteristics. This article describes the methodology used to develop the Residual Lesion Score from the previously developed Technical Performance Score for five common congenital cardiac procedures using the RAND Delphi methodology.

Methods:

A panel of 11 experts from the field of paediatric and congenital cardiology and cardiac surgery, 2 co-chairs, and a consultant were assembled to review and comment on validity and feasibility of measuring the sub-components of intraoperative and discharge Residual Lesion Score for five congenital cardiac procedures. In the first email round, the panel reviewed and commented on the Residual Lesion Score and provided validity and feasibility scores for sub-components of each of the five procedures. In the second in-person round, email comments and scores were reviewed and the Residual Lesion Score revised. The modified Residual Lesion Score was scored independently by each panellist for validity and feasibility and used to develop the “final” Residual Lesion Score.

Results:

The Residual Lesion Score sub-components with a median validity score of ≥7 and median feasibility score of ≥4 that were scored without disagreement and with low absolute deviation from the median were included in the “final” Residual Lesion Score.

Conclusion:

Using the RAND Delphi methodology, we were able to develop Residual Lesion Score modules for five important congenital cardiac procedures for the Pediatric Heart Network’s Residual Lesion Score study.
Life meaning constructed from dignity therapy in traditional Chinese culture: A qualitative analysis of dignity therapy generativity documents
Authors: Lin Junyi , Zhang Hong , Xi Lanxin , Liu Fang , Liu Wei , Guo Qiaohong
Published: December 2022

Objectives

To examine the thematic features of dignity therapy generativity documents of advanced cancer patients receiving chemotherapy in mainland China from the perspective of meaning-making during dignity therapy.

Methods

This is a qualitative descriptive study. Content analysis was used to analyze 24 dignity therapy generativity documents derived from a quasi-experimental trial of dignity therapy for advanced cancer patients receiving chemotherapy in a daycare center at a cancer hospital in northern China.

Results

Among the 24 advanced cancer patients whose generativity documents were analyzed, 14 were male and ranged in age from 26 to 78 years (average = 50.3). Two dimensions emerged from the data: (1) the sources of meaning in life, which consisted of social relationships, things and circumstances providing meaning in life, and (2) the ultimate meaning in life, referring to finding one’s real self and realizing the purpose in life, including personal life goals, dignity and autonomy, and morality of patients.

Significance of results

The multidimensional constructs of meaning in life with distinctive traditional Chinese cultural characteristics could provide insights into dignity-conserving care for advanced cancer patients with Chinese culture and provide evidence for refining the implementation protocol of DT through intentionally addressing the ultimate meaning of patients in the therapeutic session.
DISJUNCTION AND EXISTENCE PROPERTIES IN MODAL ARITHMETIC
Authors: KURAHASHI TAISHI , OKUDA MOTOKI
Published: December 2022

We systematically study several versions of the disjunction and the existence properties in modal arithmetic. First, we newly introduce three classes
$\mathrm {B}$
,
$\Delta (\mathrm {B})$
, and
$\Sigma (\mathrm {B})$
of formulas of modal arithmetic and study basic properties of them. Then, we prove several implications between the properties. In particular, among other things, we prove that for any consistent recursively enumerable extension T of
$\mathbf {PA}(\mathbf {K})$
with
$T \nvdash \Box \bot $
, the
$\Sigma (\mathrm {B})$
-disjunction property, the
$\Sigma (\mathrm {B})$
-existence property, and the
$\mathrm {B}$
-existence property are pairwise equivalent. Moreover, we introduce the notion of the
$\Sigma (\mathrm {B})$
-soundness of theories and prove that for any consistent recursively enumerable extension of
$\mathbf {PA}(\mathbf {K4})$
, the modal disjunction property is equivalent to the
$\Sigma (\mathrm {B})$
-soundness.
Sustainability of Regional Groundwater Quality in Response to Managed Aquifer Recharge
Authors: Guo Zhilin , Fogg Graham E. , Chen Kewei , Pauloo Rich , Zheng Chunmiao
Published: December 2022

Growing demands on water supply worldwide have resulted in aquifer overdraft in many regions, especially in alluvial basins under intensive irrigation. This further leads to serious deterioration of groundwater quality. Managed aquifer recharge (MAR) has been shown to mitigate groundwater overdraft, but whether MAR can actually stabilize or reverse the ongoing declines in regional groundwater quality caused by non‐point sources has not been demonstrated. This study was intended to address the question by investigating impacts of different MAR strategies on regional groundwater quality. A geostatistical model was first used to characterize a heterogeneous alluvial aquifer system in a portion of the Tulare Lake Basin. Three‐dimensional numerical models were then employed to simulate groundwater flow and mass transport. Next, MAR strategies were applied in locations with different geological conditions or joint with different irrigation activities, and their performances were evaluated. Results demonstrate the potential of significant, long‐term benefits for regional groundwater quality by applying strategic, high‐intensity recharge operations on geologically favorable subregions. Siting MAR above the incised valley fill (IVF) deposit, a near‐surface paleochannel containing unusually coarse, high‐conductivity hydrofacies, leads to more extensive improvement in the groundwater quality in terms of salinity due to significant vertical flow and lateral outward flow from the IVF. Overall, decades would be required to alleviate groundwater quality concerns in the studied 189 km2 region. The simulations indicate that the deep concentrations remain below the secondary maximum contaminant level as the solute mass migrates downward with the prominent contribution from the attenuation via dispersion and matrix diffusion.
Hydrologic and Landscape Controls on Dissolved Organic Matter Composition Across Western North American Arctic Lakes
Authors: Kurek Martin R. , Garcia‐Tigreros Fenix , Wickland Kimberly P. , Frey Karen E. , Dornblaser Mark M. , Striegl Robert G. , Niles Sydney F. , McKenna Amy M. , Aukes Pieter J. K. , Kyzivat Ethan D. , Wang Chao , Pavelsky Tamlin M. , Smith Laurence C. , Schiff Sherry L. , Butman David , Spencer Robert G. M.
Published: December 2022

Northern high‐latitude lakes are hotspots for cycling dissolved organic carbon (DOC) inputs from allochthonous sources to the atmosphere. However, the spatial distribution of lake dissolved organic matter (DOM) is largely unknown across Arctic‐boreal regions with respect to the surrounding landscape. We expand on regional studies of northern high‐latitude DOM composition by integrating DOC concentrations, optical properties, and molecular‐level characterization from lakes spanning the Canadian Taiga to the Alaskan Tundra. Lakes were sampled during the summer from July to early September to capture the growing season. DOM became more optically processed and molecular‐level aromaticity increased northward across the Canadian Shield to the southern Arctic and from interior Alaska to the Tundra, suggesting relatively greater DOM incorporation from allochthonous sources. Using water isotopes (δ18O‐H2O), we report a weak overall trend of increasing DOC and decreasing aromaticity in lakes that were hydrologically isolated from the landscape and enriched in δ18O‐H2O, while within‐region trends were stronger and varied depending on the landscape. Finally, DOC correlated weakly with chromophoric dissolved organic matter (CDOM) across the study sites, suggesting that autochthonous and photobleached DOM were a major component of the DOC in these regions; however, some of the northernmost and wetland‐dominated lakes followed pan‐Arctic riverine DOC‐CDOM relationships, indicating strong contributions from allochthonous inputs. As many lakes across the North American Arctic are experiencing changes in temperature and precipitation, we expect the proportions of allochthonous and autochthonous DOM to respond with aquatic optical browning with greater landscape connectivity and more internally produced DOM in hydrologically isolated lakes.
Enrichment of Organic Acids in Fine Particles Over a Megacity in South China
Authors: Fu Xuewei , Zhang Runqi , Li Sheng , Fang Hua , Yu Qingqing , Song Wei , Zhang Yanli , Wang Xinming
Published: December 2022

Organic acids are abundant aerosol components that impact the hygroscopicity and multiphase processes of particulate matter, yet their changing compositions and sources are poorly understood. In this study, filter‐based PM2.5 samples were collected concurrently at three sites (urban, rural, and coastal) during the summer and winter of 2018 in the megacity Guangzhou, south China, to determine organic acids including C9–C32 fatty acids, C4–C10 dicarboxylic acids, and aromatic acids. On average, the total concentrations of the speciated organic acids were higher in winter than in summer, and were the highest at the urban site. Compared to observations at the same sites in winter 2009, average concentrations of organic acids in winter 2018 increased by 35.0%, 66.0%, and −3.2% at the urban, rural and coastal sites, while their fractions in organic matter (OM) increased by approximately 261.5%, 266.7%, and 61.1%, and their fractions in PM2.5 increased by approximately 318.2%, 308.7%, and 221.1%, respectively. Source apportionment of organic acids revealed that cooking emission and vehicle exhaust were the major sources at the urban site, plant wax and vehicle exhaust were the two largest sources at the rural site with substantial contributions from biomass burning in winter, while vehicle exhaust and ship emission were the two major sources at the coastal site. Less contributions from secondary production were retrieved in winter 2018 than in winter 2009, and the enrichment of organic acids in PM2.5 or OM was attributed to their elevated primary emissions from vehicles and ships, cooking, and plant wax.
Season‐Dependent Modulation of Pacific Meridional Mode on Tropical Cyclone Genesis Over the Western North Pacific
Authors: Fu Meiling , Wang Chao , Wu Liguang , Zhao Haikun
Published: December 2022

Pacific Meridional Mode (PMM) has been found to be significantly correlated with tropical cyclone (TC) genesis in the western North Pacific (WNP), while the seasonality in their relationship remains unknown. Here we found that their relationship experiences remarkable seasonality, with a significant positive correlation in January–April and August–December but an insignificant relationship in May–July. This seasonality stems from the diverse responses of large‐scale conditions to the different magnitude of the PMM‐related sea surface temperature (SST) warming that is dependent on the strength of trade wind in the three seasons. In January–July, strong trade wind facilitates great PMM SST warming that stimulates large‐scale ascending motion in the eastern WNP but compensated descending motion in the western WNP, favoring TC genesis in January–April because its main genesis region is in the eastern WNP. However, the main genesis region extends to the whole WNP in May–July, the inconsistent large‐scale condition anomalies across the western and eastern WNP thus lead to the insignificant relationship in May–July. In August–December, the PMM‐related SST warming and the associated ascending motion fade away due to the much‐weakened trade wind, and the favorable large‐scale ascending motion over the whole WNP is linked to the PMM‐related SST cooling induced descending motion through a modification of the Walker circulation. The results highlight the season‐dependent mechanism of PMM influencing TC genesis and have some insights for improving seasonal forecasting.
Testing Hidden Assumptions of Representativeness in Reach‐Scale Studies of Hyporheic Exchange
Authors: Becker Paige S. , Ward Adam S. , Herzog Skuyler P. , Wondzell Steven M.
Published: December 2022

Field studies of hyporheic exchange in mountain systems are often conducted using short study reaches and a limited number of observations. It is common practice to assume these study reaches represent hyporheic exchange at larger scales or different sites and to infer general relationships among potential causal mechanisms from the limited number of observations. However, these assumptions of representativeness are rarely tested. In this study, we develop numerical models from four segments of mountain streams in different geomorphologic settings and extract shorter reaches to test how representative exchange metrics are in shorter reaches compared to their reference segments. We also map the locations of the representative reaches to determine if a pattern exists based on location. Finally, we compare variance of these shorter within‐site reaches to 29 additional reaches across the same basin to understand the impacts of inferring causal mechanisms, for example, the expectation that wide and narrow valley bottoms will yield different hyporheic exchange patterns. Our results show that the location and length strategy of the study reach must be considered before assuming an exchange metric to be representative of anything other than the exact segment studied. Further, it is necessary to quantify within and between site variations before making causal inferences based on observable characteristics, such as valley width or stream morphology. Our findings have implications for future field practices and how those practices are translated into models.
Multifaceted functions of STING in human health and disease: from molecular mechanism to targeted strategy
Authors: Zhang Zili , Zhou Haifeng , Ouyang Xiaohu , Dong Yalan , Sarapultsev Alexey , Luo Shanshan , Hu Desheng
Published: December 2022

Since the discovery of Stimulator of Interferon Genes (STING) as an important pivot for cytosolic DNA sensation and interferon (IFN) induction, intensive efforts have been endeavored to clarify the molecular mechanism of its activation, its physiological function as a ubiquitously expressed protein, and to explore its potential as a therapeutic target in a wide range of immune-related diseases. With its orthodox ligand 2’3’-cyclic GMP–AMP (2’3’-cGAMP) and the upstream sensor 2’3’-cGAMP synthase (cGAS) to be found, STING acquires its central functionality in the best-studied signaling cascade, namely the cGAS–STING–IFN pathway. However, recently updated research through structural research, genetic screening, and biochemical assay greatly extends the current knowledge of STING biology. A second ligand pocket was recently discovered in the transmembrane domain for a synthetic agonist. On its downstream outputs, accumulating studies sketch primordial and multifaceted roles of STING beyond its cytokine-inducing function, such as autophagy, cell death, metabolic modulation, endoplasmic reticulum (ER) stress, and RNA virus restriction. Furthermore, with the expansion of the STING interactome, the details of STING trafficking also get clearer. After retrospecting the brief history of viral interference and the milestone events since the discovery of STING, we present a vivid panorama of STING biology taking into account the details of the biochemical assay and structural information, especially its versatile outputs and functions beyond IFN induction. We also summarize the roles of STING in the pathogenesis of various diseases and highlight the development of small-molecular compounds targeting STING for disease treatment in combination with the latest research. Finally, we discuss the open questions imperative to answer.
Tumour-infiltrating lymphocytes: from prognosis to treatment selection
Authors: Brummel Koen , Eerkens Anneke L. , de Bruyn Marco , Nijman Hans W.
Published: December 2022

Tumour-infiltrating lymphocytes (TILs) are considered crucial in anti-tumour immunity. Accordingly, the presence of TILs contains prognostic and predictive value. In 2011, we performed a systematic review and meta-analysis on the prognostic value of TILs across cancer types. Since then, the advent of immune checkpoint blockade (ICB) has renewed interest in the analysis of TILs. In this review, we first describe how our understanding of the prognostic value of TIL has changed over the last decade. New insights on novel TIL subsets are discussed and give a broader view on the prognostic effect of TILs in cancer. Apart from prognostic value, evidence on the predictive significance of TILs in the immune therapy era are discussed, as well as new techniques, such as machine learning that strive to incorporate these predictive capacities within clinical trials.
Unconventional exciton evolution from the pseudogap to superconducting phases in cuprates
Authors: Singh A. , Huang H. Y. , Xie J. D. , Okamoto J. , Chen C. T. , Watanabe T. , Fujimori A. , Imada M. , Huang D. J.
Published: December 2022

Electron quasiparticles play a crucial role in simplifying the description of many-body physics in solids with surprising success. Conventional Landau’s Fermi-liquid and quasiparticle theories for high-temperature superconducting cuprates have, however, received skepticism from various angles. A path-breaking framework of electron fractionalization has been established to replace the Fermi-liquid theory for systems that show the fractional quantum Hall effect and the Mott insulating phenomena; whether it captures the essential physics of the pseudogap and superconducting phases of cuprates is still an open issue. Here, we show that excitonic excitation of optimally doped Bi2Sr2CaCu2O8+δ with energy far above the superconducting-gap energy scale, about 1 eV or even higher, is unusually enhanced by the onset of superconductivity. Our finding proves the involvement of such high-energy excitons in superconductivity. Therefore, the observed enhancement in the spectral weight of excitons imposes a crucial constraint on theories for the pseudogap and superconducting mechanisms. A simple two-component fermion model which embodies electron fractionalization in the pseudogap state provides a possible mechanism of this enhancement, pointing toward a novel route for understanding the electronic structure of superconducting cuprates.
Iron-mediated ligand-to-metal charge transfer enables 1,2-diazidation of alkenes
Authors: Zhang Muliang , Zhang Jinghui , Li Qingyao , Shi Yumeng
Published: December 2022

Given the widespread significance of vicinal diamine units in organic synthesis, pharmaceuticals and functional materials, as well as in privileged molecular catalysts, an efficient and practical strategy that avoids the use of stoichiometric strong oxidants is highly desirable. We herein report the application of ligand-to-metal charge transfer (LMCT) excitation to 1,2-diazidation reactions from alkenes and TMSN3 via a coordination-LMCT-homolysis process with more abundant and greener iron salt as the catalyst. Such a LMCT-homolysis mode allows the generation of electrophilic azidyl radical intermediate from Fe–N3 complexes poised for subsequent radical addition into carbon–carbon double bond. The generated carbon radical intermediate is further captured by iron-mediated azidyl radical transfer, enabling dual carbon–nitrogen bond formation. This protocol provides a versatile platform to access structurally diverse diazides with high functional group compatibility from readily available alkenes without the need of chemical oxidants.
Exon junction complex shapes the m6A epitranscriptome
Authors: Yang Xin , Triboulet Robinson , Liu Qi , Sendinc Erdem , Gregory Richard I.
Published: December 2022

N6-methyladenosine (m6A), the most abundant modification of mRNA, is essential for normal development and dysregulation promotes cancer. m6A is highly enriched in the 3’ untranslated region (UTR) of a large subset of mRNAs to influence mRNA stability and/or translation. However, the mechanism responsible for the observed m6A distribution remains enigmatic. Here we find the exon junction complex shapes the m6A landscape by blocking METTL3-mediated m6A modification close to exon junctions within coding sequence (CDS). Depletion of EIF4A3, a core component of the EJC, causes increased METTL3 binding and m6A modification of short internal exons, and sites close to exon-exon junctions within mRNA. Reporter gene experiments further support the role of splicing and EIF4A3 deposition in controlling m6A modification via the local steric blockade of METTL3. Our results explain how characteristic patterns of m6A mRNA modification are established and uncover a role of the EJC in shaping the m6A epitranscriptome.
Exploiting ferrofluidic wetting for miniature soft machines
Authors: Sun Mengmeng , Hao Bo , Yang Shihao , Wang Xin , Majidi Carmel , Zhang Li
Published: December 2022

Miniature magnetic soft machines could significantly impact minimally invasive robotics and biomedical applications. However, most soft machines are limited to solid magnetic materials, whereas further progress also relies on fluidic constructs obtained by reconfiguring liquid magnetic materials, such as ferrofluid. Here we show how harnessing the wettability of ferrofluids allows for controlled reconfigurability and the ability to create versatile soft machines. The ferrofluid droplet exhibits multimodal motions, and a single droplet can be controlled to split into multiple sub-droplets and then re-fuse back on demand. The soft droplet machine can negotiate changing terrains in unstructured environments. In addition, the ferrofluid droplets can be configured as a liquid capsule, enabling cargo delivery; a wireless omnidirectional liquid cilia matrix capable of pumping biofluids; and a wireless liquid skin, allowing multiple types of miniature soft machine construction. This work improves small magnetic soft machines’ achievable complexity and boosts their future biomedical applications capabilities.