bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK
Authors: Shields Adrian M , Anantharachagan Ariharan , Arumugakani Gururaj , Baker Kenneth , Bahal Sameer , Baxendale Helen , Bermingham William , Bhole Malini , Boules Evon , Bright Philip , Chopra Charu , Cliffe Lucy , Cleave Betsy , Dempster John , Devlin Lisa , Dhalla Fatima , Diwakar Lavanya , Drewe Elizabeth , Duncan Christopher , Dziadzio Magdalena , Elcombe Suzanne , Elkhalifa Shuayb , Gennery Andrew , Ghanta Harichandrana , Goddard Sarah , Grigoriadou Sofia , Hackett Scott , Hayman Grant , Herriot Richard , Herwadkar Archana , Huissoon Aarnoud , Jain Rashmi , Jolles Stephen , Johnston Sarah , Khan Sujoy , Laffan James , Lane Peter , Leeman Lucy , Lowe David M , Mahabir Shanti , Lochlainn Dylan James Mac , McDermott Elizabeth , Misbah Siraj , Moghaddas Fiona , Morsi Hadeil , Murng Sai , Noorani Sadia , O’Brien Rachael , Patel Smita , Price Arthur , Rahman Tasneem , Seneviratne Suranjith , Shrimpton Anna , Stroud Catherine , Thomas Moira , Townsend Katie , Vaitla Prashantha , Verma Nisha , Williams Anthony , Burns Siobhan O , Savic Sinisa , Richter Alex G 
Published: January 2022

Abstract
In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to the hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir, and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count, and the presence of co-morbidities are additional risk factors for poor outcome in this cohort.
Causal mediation analysis with double machine learning
Authors: Farbmacher Helmut , Huber Martin , Lafférs Lukáš , Langen Henrika , Spindler Martin 
Published: January 2022

SummaryThis paper combines causal mediation analysis with double machine learning for a data-driven control of observed confounders in a high-dimensional setting. The average indirect effect of a binary treatment and the unmediated direct effect are estimated based on efficient score functions, which are robust with respect to misspecifications of the outcome, mediator, and treatment models. This property is key for selecting these models by double machine learning, which is combined with data splitting to prevent overfitting. We demonstrate that the effect estimators are asymptotically normal and $n^{-1/2}$-consistent under specific regularity conditions and investigate the finite sample properties of the suggested methods in a simulation study when considering lasso as machine learner. We also provide an empirical application to the US National Longitudinal Survey of Youth, assessing the indirect effect of health insurance coverage on general health operating via routine checkups as mediator, as well as the direct effect.
Sodium-containing acetaminophen and cardiovascular outcomes in individuals with and without hypertension
Authors: Zeng Chao , Rosenberg Lynn , Li Xiaoxiao , Djousse Luc , Wei Jie , Lei Guanghua , Zhang Yuqing 
Published: January 2022

Abstract

Aims
Previous studies have found high sodium intake to be associated with increased risks of cardiovascular disease (CVD) and all-cause mortality among individuals with hypertension; findings on the effect of intake among individuals without hypertension have been equivocal. We aimed to compare the risks of incident CVD and all-cause mortality among initiators of sodium-containing acetaminophen with the risk of initiators of non-sodium-containing formulations of the same drug according to the history of hypertension.

Methods and results
Using The Health Improvement Network, we conducted two cohort studies among individuals with and without hypertension. We examined the relation of sodium-containing acetaminophen to the risk of each outcome during 1-year follow-up using marginal structural models with an inverse probability weighting to adjust for time-varying confounders. The outcomes were incident CVD (myocardial infarction, stroke, and heart failure) and all-cause mortality. Among individuals with hypertension (mean age: 73.4 years), 122 CVDs occurred among 4532 initiators of sodium-containing acetaminophen (1-year risk: 5.6%) and 3051 among 146 866 non-sodium-containing acetaminophen initiators (1-year risk: 4.6%). The average weighted hazard ratio (HR) was 1.59 [95% confidence interval (CI) 1.32–1.92]. Among individuals without hypertension (mean age: 71.0 years), 105 CVDs occurred among 5351 initiators of sodium-containing acetaminophen (1-year risk: 4.4%) and 2079 among 141 948 non-sodium-containing acetaminophen initiators (1-year risk: 3.7%), with an average weighted HR of 1.45 (95% CI 1.18–1.79). Results of specific CVD outcomes and all-cause mortality were similar.

Conclusion
The initiation of sodium-containing acetaminophen was associated with increased risks of CVD and all-cause mortality among individuals with or without hypertension. Our findings suggest that individuals should avoid unnecessary excessive sodium intake through sodium-containing acetaminophen use.
Microbial biogeography of acid mine drainage sediments at a regional scale across southern China
Authors: Hao Yi-Qi , Zhao Xin-Feng , Ai Hong-Xia , Gao Shao-Ming , Teng Wen-Kai , Zheng Jin , Shu Wen-Sheng 
Published: January 2022

AbstractInvestigations of microbial biogeography in extreme environments provide unique opportunities to disentangle the roles of environment and space in microbial community assembly. Here, we reported a comprehensive microbial biogeographic survey of 90 acid mine drainage (AMD) sediment samples from 18 mining sites of various mineral types across southern China. We found that environmental selection was strong in determining the AMD habitat species pool. However, microbial alpha diversity was primarily explained by mining sites rather than environmental factors, and microbial beta diversity correlated more strongly with geographic than environmental distance at both large and small spatial scales. Particularly, the presence/absence of widespread AMD habitat generalists was only correlated with geographic distance and independent of environmental variation. These distance–decay patterns suggested that spatial processes played a more important role in determining microbial compositional variation across space; which could be explained by the reinforced impacts of dispersal limitation in less fluid, spatially structured sediment habitat with diverse pre-existing communities. In summary, our findings suggested that the deterministic assembling and spatial constraints interact to shape microbial biogeography in AMD sediments; and provided implications that spatial processes should be considered when predicting microbial dynamics in response to severe environmental change across large spatial scales.
Error estimates for finite differences approximations of the total variation
Authors: Caillaud Corentin , Chambolle Antonin 
Published: January 2022

AbstractWe present a convergence rate analysis of the Rudin–Osher–Fatemi (ROF) denoising problem for two different discretizations of the total variation. The first is the standard discretization, which induces blurring in some particular diagonal directions. We prove that in a simplified setting corresponding to such a direction, the discrete ROF energy converges to the continuous one with the rate $h^{2/3}$. The second discretization is based on dual Raviart–Thomas fields and achieves an optimal $O(h)$ convergence rate for the same quantity, for discontinuous solutions with some standard hypotheses.
Balancing Statistical Power and Risk in HIV Cure Clinical Trial Design
Authors: Lau Jillian S Y , Cromer Deborah , Pinkevych Mykola , Lewin Sharon R , Rasmussen Thomas A , McMahon James H , Davenport Miles P 
Published: January 2022

Abstract

Background
Analytical treatment interruptions (ATI) are pauses of antiretroviral therapy (ART) in the context of human immunodeficiency virus (HIV) cure trials. They are the gold standard in determining if interventions being tested can achieve sustained virological control in the absence of ART. However, withholding ART comes with risks and discomforts to trial participant. We used mathematical models to explore how ATI study design can be improved to maximize statistical power, while minimizing risks to participants.

Methods
Using previously observed dynamics of time to viral rebound (TVR) post-ATI, we modelled estimates for optimal sample size, frequency, and ATI duration required to detect a significant difference in the TVR between control and intervention groups. Groups were compared using a log-rank test, and analytical and stochastic techniques.

Results
In placebo-controlled TVR studies, 120 participants are required in each arm to detect 30% difference in frequency of viral reactivation at 80% power. There was little statistical advantage to measuring viral load more frequently than weekly, or interrupting ART beyond 5 weeks in a TVR study.

Conclusions
Current TVR HIV cure studies are underpowered to detect statistically significant changes in frequency of viral reactivation. Alternate study designs can improve the statistical power of ATI trials.
Vaccines alone are no silver bullets: a modeling study on the impact of efficient contact tracing on COVID-19 infection and transmission in Malaysia
Authors: Baha Raja Dhesi , Abdul Taib Nur Asheila , Teo Alvin Kuo Jing , Jayaraj Vivek Jason , Ting Choo-Yee 
Published: January 2022

Abstract

Background
The computer simulation presented in this study aimed to investigate the effect of contact tracing on coronavirus disease 2019 (COVID-19) transmission and infection in the context of rising vaccination rates.

Methods
This study proposed a deterministic, compartmental model with contact tracing and vaccination components. We defined contact tracing effectiveness as the proportion of contacts of a positive case that was successfully traced and the vaccination rate as the proportion of daily doses administered per population in Malaysia. Sensitivity analyses on the untraced and infectious populations were conducted.

Results
At a vaccination rate of 1.4%, contact tracing with an effectiveness of 70% could delay the peak of untraced asymptomatic cases by 17 d and reduce it by 70% compared with 30% contact tracing effectiveness. A similar trend was observed for symptomatic cases when a similar experiment setting was used. We also performed sensitivity analyses by using different combinations of contact tracing effectiveness and vaccination rates. In all scenarios, the effect of contact tracing on COVID-19 incidence persisted for both asymptomatic and symptomatic cases.

Conclusions
While vaccines are progressively rolled out, efficient contact tracing must be rapidly implemented concurrently to reach, find, test, isolate and support the affected populations to bring COVID-19 under control.
Beyond Citation Metrics: A Pilot Scoping Review to Rapidly Characterize Article Impact
Authors: Rubinstein Matthew L 
Published: January 2022

Abstract

Background
Systematic reviews and meta-analyses (SRMAs) support evidence-based practice in laboratory medicine. However, there is little in the literature to address the challenge of globally characterizing the impact of SRMA findings and recommendations. We propose that characterization of citing studies through the structured methods of scoping review provides a meaningful window.

Content
A scoping review method characterized the impact of a test utilization SRMA’s findings and recommendations through use of a 17-item structured charting template. Following charting, we used descriptive content analysis to identify patterns of utilization, while incorporating current conceptual thinking on healthcare quality improvement.

Summary
Rapid scoping reviews support descriptive characterization of SRMA impact and linkage of studies to evolving concepts in the quality improvement literature. The approach may be especially appealing to communities of practice, e.g., to support reflective practice. This pilot suggests that primary studies that have cited the 2018 SRMA have utilized some, but not all, aspects of the 2018 SRMA.
Secrecy by Default: How Regional Trade Agreements Reshape Protection of Source Code
Authors: Słok-Wódkowska Magdalena , Mazur Joanna 
Published: January 2022

ABSTRACT
A growing number of regional trade agreements include articles prohibiting access to or the transfer of source code as a condition of the import, distribution, sale, or use of software. We challenge this new approach to protecting source code in international economic law. Using Katharina Pistor’s theory of the ‘code of capital’, we find that this approach protects source code as capital at the expense of the regulatory power of states. The new approach differs from existing ways of protecting source code as well as from the protection based on copyrights, patents, trade secrecy, and provisions on forced technology transfer. We show that it establishes the secrecy of source code by default and leaves only a small window for states to require access to source code.
Clinical characteristics of undifferentiated pleomorphic sarcoma of bone and the impact of adjuvant chemotherapy on the affected patients: a population-based cohort study
Authors: Kobayashi Hiroshi , Zhang Liuzhe , Hirai Toshihide , Tsuda Yusuke , Ikegami Masachika , Tanaka Sakae 
Published: January 2022

Abstract

Background
Clinical characteristics of undifferentiated pleomorphic sarcoma of bone are not elucidated. Herein, we clarify its clinical features and analyze the efficacy of adjuvant chemotherapy in patients with undifferentiated pleomorphic sarcoma of bone.

Methods
Prognostic factors and estimated disease-specific survival in 247 patients with primary undifferentiated pleomorphic sarcoma of bone were identified from a registry in Japan. The effect of adjuvant chemotherapy was evaluated in localized resectable cases, and the characteristics of the two groups treated with or without chemotherapy were adjusted using propensity score matching.

Results
The 5-year disease-specific survival rates were 47.4% in the entire cohort and 56.4 and 16.9% in the M0 and M1 groups, respectively. Multivariate disease-specific survival analysis revealed that metastasis on initial presentation and age ≥ 65 years were poor prognostic factors. Overall, 132 localized and resectable primary lesions were extracted. Adjuvant chemotherapy administration was a favorable prognostic factor (hazard ratio: 0.43, P = 0.04), and it significantly prolonged disease-specific survival compared with no adjuvant chemotherapy (5-year disease-specific survival: 78.8% vs. 51.8%, P = 0.008). Adjuvant chemotherapy prolonged disease-specific survival in patients with tumor size &lt;8 cm (5-year disease-specific survival: 100% vs. 54.6%, P = 0.02); however, its efficacy decreased in those with tumor size ≥8 cm (5-year disease-specific survival: 68.7% vs. 42%, P = 0.09). After propensity score matching, adjuvant chemotherapy was significantly associated with good disease-specific survival (P = 0.02).

Conclusions
Metastasis in the initial presentation was the poorest prognostic factor. On evaluating localized and resectable cases only, adjuvant chemotherapy significantly improved disease-specific survival, although its effect decreased in cases with large tumors.
Political Bioethics
Authors: Gregg Benjamin 
Published: January 2022

AbstractIf bioethical questions cannot be resolved in a widely acceptable manner by rational argument, and if they can be regulated only on the basis of political decision-making, then bioethics belongs to the political sphere. The particular kind of politics practiced in any given society matters greatly: it will determine the kind of bioethical regulation, legislation, and public policy generated there. I propose approaching bioethical questions politically in terms of decisions that cannot be “correct” but that can be “procedurally legitimate.” Two procedures in particular can deliver legitimate bioethical decisions, once combined: expert bioethics committees and deliberative democracy. Bioethics so understood can exceed bioethics as a moral project or as a set of administrative principles to regulate medical practice; it can now aspire to a democratic project that involves ordinary citizens as far as reasonably possible. I advance this argument in four steps: (1) using the example of human germline gene editing, (2) I propose a general understanding of proceduralism, and (3) then combine two types and (4) conclude with a defense of majoritarian proceduralism. I develop this argument in terms of one example: germline gene editing.
Impacts of phosphatidylglycerol on plastid gene expression and light induction of nuclear photosynthetic genes
Authors: Fujii Sho , Kobayashi Koichi , Lin Ying-Chen , Liu Yu-chi , Nakamura Yuki , Wada Hajime 
Published: January 2022

Abstract
Phosphatidylglycerol (PG) is the only major phospholipid in the thylakoid membrane of chloroplasts. PG is essential for photosynthesis, and loss of PG in Arabidopsis thaliana results in severe defects of growth and chloroplast development, with decreased chlorophyll accumulation, impaired thylakoid formation, and down-regulation of photosynthesis-associated genes encoded in nuclear and plastid genomes. However, how the absence of PG affects gene expression and plant growth remains unclear. To elucidate this mechanism, we investigated transcriptional profiles of a PG-deficient Arabidopsis mutant pgp1-2 under various light conditions. Microarray analysis demonstrated that reactive oxygen species (ROS)-responsive genes were up-regulated in pgp1-2. However, ROS production was not enhanced in the mutant even under strong light, indicating limited impacts of photooxidative stress on the defects of pgp1-2. Illumination to dark-adapted pgp1-2 triggered down-regulation of photosynthesis-associated nuclear-encoded genes (PhANGs), while plastid-encoded genes were constantly suppressed. Overexpression of GOLDEN2-LIKE1 (GLK1), a transcription factor gene regulating chloroplast development, in pgp1-2 up-regulated PhANGs but not plastid-encoded genes along with chlorophyll accumulation. Our data suggest a broad impact of PG biosynthesis on nuclear-encoded genes partially via GLK1 and a specific involvement of this lipid in plastid gene expression and plant development.
Investigation of Cases (II)
Authors: de Pablo Alfonso Lamadrid , Kellerbauer Manuel 
Published: January 2022

Abstract
This chapter explores formal investigative measures in general, requests for information, and interviews. The European Commission is empowered to investigate possible infringements of Articles 101 and 102 of the Treaty on the Functioning of the European Union (TFEU) and, where appropriate, impose penalties on undertakings and associations of undertakings. To this end, it performs the activities both of fact-finding and evaluation. Often, the Commission needs to take investigatory steps to establish with certainty the existence of the suspected infringements. In that respect, its central role in the application of the principles laid down in Articles 101 and 102 TFEU has been maintained and its powers of investigation granted under Regulation 17 have been further strengthened. As before, its two principal instruments are requests for information and on-site inspections. In addition, the Commission has been explicitly empowered to conduct interviews of natural or legal persons.
Infringement Decisions and Penalties
Authors: Sauer Ralf , Kellerbauer Manuel 
Published: January 2022

Abstract
This chapter discusses infringement decisions and penalties. There is no specific requirement for the European Commission as to the way in which it structures competition decisions, but they must meet the requirements contained in Article 296 of the Treaty on the Functioning of the European Union (TFEU). The basic layout of decisions applying Articles 101 and 102 TFEU consists of (i) a title; (ii) a preamble referencing the legal basis; (iii) recitals that contain a summary of the various procedural steps, an account of the facts, a legal assessment of those facts, as well as, where applicable, an explanation of the level of any sanctions (fines, penalty payments); and (iv) the Articles of the decision, known as the operative part or simply the ‘decision’. The operative part sets out the finding of an infringement and its duration for specific addressees (legal entities), the remedies required by the Commission, the amounts of any sanctions with arrangements for their payment, and an indication that the decision shall be enforceable pursuant to Article 299 TFEU. The chapter then focuses on infringement decisions, with particular attention paid to the operative part. This also includes declaratory decisions, orders to bring an infringement to an end and the imposition of remedies, as well as fines and periodic penalty payments imposed on undertakings for infringements of the substantive provisions of Articles 101 and 102 TFEU.
General Issues
Authors: Araujo Boyd Marcos , Lingen Nicolas von 
Published: January 2022

Abstract
This chapter studies the scope of the Merger Control Regulation. Council Regulation (EC) 139/2004 on the control of concentrations between undertakings (Merger Control Regulation or MCR) sets out a common merger control in all Member States of the European Union. It is based on the necessity of ensuring that corporate transactions do not distort competition between undertakings, while ensuring a level playing field between undertakings operating in the different Member States. In parallel to the Merger Control Regulation, Article 57 of the Agreement on the European Economic Area (EEA Agreement) extends the merger control regime to the geographic ambit of the European Economic Area. Under the EEA Agreement, if a concentration meets the turnover thresholds of the Merger Control Regulation, the European Commission has sole competence to decide on the concentration. Concentrations with an ‘EFTA [European Free Trade Association] dimension’ as defined in Article 57 of the EEA Agreement and not having an EU dimension are dealt with by the EFTA Surveillance Authority (ESA). However, to date, no such concentrations have been notified to the EFTA Surveillance Authority. Where the Commission handles cases as a consequence of its competence under the EEA Agreement, ESA and the competition authorities of the EFTA States are involved in the proceedings.