bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positioning Filgotinib in the Treatment Algorithm of Moderate to Severe Ulcerative Colitis
Authors: D’Amico Ferdinando , Magro Fernando , Peyrin-Biroulet Laurent , Danese Silvio 
Published: November 2021

AbstractBackground and AimsFilgotinib is a small molecule that selectively inhibits Janus kinase [JAK] type 1. It is already approved for the treatment of rheumatoid arthritis and is being evaluated for the management of patients with moderate to severe ulcerative colitis [UC]. The purpose of this review is to provide an overview of the currently available data on filgotinib and to define how to position this new drug in the treatment algorithm of patients with UC.MethodsThe Pubmed, Embase and Scopus databases were searched up to June 25, 2021 in order to identify studies reporting efficacy and safety data of filgotinib in patients with UC.ResultsData from a phase III study enrolling UC patients with moderate to severe disease show that filgotinib is effective with a reassuring safety profile. Filgotinib treatment is not associated with a greater risk of thrombosis and herpes zoster infections compared to other JAK inhibitors. However, animal studies reported impaired spermatogenesis and histopathological effects on male reproductive organs, making it necessary to deepen this aspect in dedicated human studies.ConclusionsFilgotinib is an effective and safe drug for treatment of both biologic-naive and biologic-experienced patients with moderate to severe UC and may soon be available.
Multicentric randomized evaluation of a tricuspid valve percutaneous repair system (clip for the tricuspid valve) in the treatment of severe secondary tricuspid regurgitation Tri.Fr Design paper
Authors: Donal Erwan , Leurent Guillaume , Ganivet Anne , Lurz Philip , Coisne Augustin , De Groote Pascal , Lafitte Stephane , Leroux Lionel , Karam Nicole , Biere Loic , Rouleau Frederic , Sportouch Catherine , Dreyfus Julien , Nejjari Mohammed , Josselin Jean-Michel , Anselmi Amedeo , Galli Elena , Bajeux Emma , Guerin Patrice , Obadia Jean-François , Trochu Jean-Noel , Oger Emmanuel 
Published: November 2021

Abstract

Aims
Tricuspid regurgitation (TR) is associated with significant morbidity and mortality. Its independent prognostic role has been repeatedly demonstrated. However, this valvular heart condition is largely undertreated because of the increased risk of surgical repair. Recently, transcatheter techniques for the treatment of TR have emerged, but their implications for the clinical endpoints are still unknown.

Methods and results
The Tri.fr trial will be a multicentre, controlled, randomized (1:1 ratio), superior, open-label, and parallel-group study conducted in 300 patients with severe secondary TR that is considered non-surgical by heart teams. Inclusion will be possible only after core laboratory review of transthoracic and transoesophageal echocardiography and after validation by the clinical eligibility committee. A description of the mechanisms of the TR will be conducted by the core laboratory. Atrial or ventricular impacts on the severity of the secondary TR will be taken into account for the randomization. The patients will be followed for 12-month, and the primary outcome will be the Packer composite clinical endpoint [combining New York Heart Association class, patient global assessment (PGA), and major cardiovascular events]. It will test the hypothesis that a tricuspid valve percutaneous repair strategy using a clip dedicated to the tricuspid valve is superior to best guideline-directed medical therapy in symptomatic patients with severe secondary TR.

Conclusion
Tri.fr will be the first randomized, academic, multicentre study testing the value of percutaneous correction in patients with severe secondary TR.
Quality improvement initiative in paediatric echocardiography laboratory in a low- to middle-income country
Authors: Mohsin Shazia , Hasan Babar , Ather Mishaal , Ali Salima Ashiq , Aslam Nadeem , Khalid Farah , Shabbir Zain Adil , Shabbir Shaan Adil , Chowdhury Devyani 
Published: November 2021

Abstract

Aims
To determine the impact of a quality improvement (QI) initiative in the area of paediatric echocardiography (echo) in a low- to middle-income country (LMIC).
Care for patients with congenital heart disease is challenging, especially in LMICs. Collaborative learning through QI projects is imperative to ensure improvement in delivery processes leading to better patient outcomes.

Methods and results
This QI initiative was taken by a team consisting of physicians and sonographers. Problems were identified, a key driver diagram (KDD) was created, and simple process re-engineering was done using interventions based on the KDD. Metrics (five process and one outcome) were assessed to determine the effectiveness of the QI project. The process metrics assessed were comprehensiveness of exam, timeliness of reporting, diagnostic accuracy and error, and sedation adverse event rates of transthoracic echocardiograms, while a novel comprehensive echo laboratory (lab) quality score was developed as an outcome metric. Data were collected quarterly and analysed in the post-implementation phase. Significant improvement was seen in comprehensive mean score (20.4–29.7), timeliness (40–95%), and diagnostic accuracy rate (91–100%), while a decrease was seen in the diagnostic error rate (7.5–3.5%) and the sedation adverse event rate (6.8–0%), pre- vs. post-implementation. The overall quality outcome score improved from 7 to 19 and the echo lab was able to achieve adequate quality.

Conclusion
This QI initiative produced improvement in all the processes, and the overall quality of the echo lab without any substantial increase in resources or cost.
Optimal follow-up after acute pulmonary embolism: a position paper of the European Society of Cardiology Working Group on Pulmonary Circulation and Right Ventricular Function, in collaboration with the European Society of Cardiology Working Group on Atherosclerosis and Vascular Biology, endorsed by the European Respiratory Society
Authors: Klok Frederikus A. , Ageno Walter , Ay Cihan , Bäck Magnus , Barco Stefano , Bertoletti Laurent , Becattini Cecilia , Carlsen Jørn , Delcroix Marion , van Es Nick , Huisman Menno V. , Jara-Palomares Luis , Konstantinides Stavros , Lang Irene , Meyer Guy , Ní Áinle Fionnuala , Rosenkranz Stephan , Pruszczyk Piotr 
Published: November 2021

Abstract
This position paper provides a comprehensive guide for optimal follow-up of patients with acute pulmonary embolism (PE), covering multiple relevant aspects of patient counselling. It serves as a practical guide to treating patients with acute PE complementary to the formal 2019 European Society of Cardiology guidelines developed with the European Respiratory Society. We propose a holistic approach considering the whole spectrum of serious adverse events that patients with acute PE may encounter on the short and long run. We underline the relevance of assessment of modifiable risk factors for bleeding, of acquired thrombophilia and limited cancer screening (unprovoked PE) as well as a dedicated surveillance for the potential development of chronic thromboembolic pulmonary hypertension as part of routine practice; routine testing for genetic thrombophilia should be avoided. We advocate the use of outcome measures for functional outcome and quality of life to quantify the impact of the PE diagnosis and identify patients with the post-PE syndrome early. Counselling patients on maintaining a healthy lifestyle mitigates the risk of the post-PE syndrome and improves cardiovascular prognosis. Therefore, we consider it important to discuss when and how to resume sporting activities soon after diagnosing PE. Additional patient-relevant topics that require Focused counselling are travel and birth control.
Ray velocity derivatives in anisotropic elastic media – Part I: general anisotropy
Authors: Koren Zvi , Ravve Igor 
Published: November 2021

SUMMARY
We present an original, generic and efficient approach for computing the first and second partial derivatives of ray (group) velocities along seismic ray paths in general anisotropic (triclinic) elastic media. As the ray velocities deliver the ray element traveltimes, this set of partial derivatives constructs the so-called kinematic and dynamic sensitivity kernels which are used in different key seismic modelling and inversion methods, such as two-point ray bending methods and seismic tomography. The second derivatives are useful in the solution of the above-mentioned kinematic problems, and they are essential for evaluating the dynamic properties along the rays (amplitudes and phases). The traveltime is delivered through an integral over a given Lagrangian defined at each point along the ray. In our approach, we use an arclength-related Lagrangian representing a reciprocal of the ray velocity magnitude. Although this magnitude cannot be explicitly expressed in terms of the medium properties and the ray direction components, its derivatives can still be formulated analytically using the corresponding arclength-related Hamiltonian that can be explicitly expressed in terms of the medium properties and the slowness vector components; this requires first to obtain (invert for) the slowness vector components, given the ray direction components. Computation of the slowness vector and the ray velocity derivatives is considerably simplified by using an auxiliary scaled-time-related Hamiltonian obtained directly from the Christoffel equation and connected to the arclength-related Hamiltonian by a simple scale factor. This study consists of two parts. In Part I, we consider general anisotropic (triclinic) media, and provide the derivatives (gradients and Hessians) of the ray velocity, with respect to (1) the spatial location and direction vectors and (2) the elastic model parameters. The derivatives are obtained for both quasi-compressional and quasi-shear waves, where other types of media, characterized with higher symmetries, can be considered particular cases. In Part II, we apply the theory of Part I explicitly to polar anisotropic media (transverse isotropy with tilted axis of symmetry, TTI), and obtain the explicit ray velocity derivatives for the coupled qP and qSV waves and for SH waves. The derivatives for polar anisotropy are simplified (as compared to general anisotropy), obviously yielding more effective computations. The ray velocity derivatives are tested by checking consistency between the proposed analytical formulae and the corresponding numerical ones.
How to dampen the surge of non-communicable diseases in Southeast Asia: insights from a systematic review and meta-analysis
Authors: Fritz Manuela , Fromell Hanna 
Published: November 2021

AbstractNon-communicable diseases (NCDs), such as diabetes, cancer, cardiovascular diseases and chronic respiratory diseases, have overtaken infectious diseases as the number one cause of death worldwide. The rise of these diseases is especially grave in Southeast Asia, where existing research however falls short on offering guidance on how policy can best prevent and control NCDs in the region. Additionally, low- and middle-income countries in Southeast Asia cannot directly incorporate lessons drawn from interventions in richer countries, since health system capacities and human and financial resources are thoroughly different. Preventive interventions, thus, need to correspond to local capacities and require contextual solutions. In this article, we provide a systematic review of a wide scope of NCD interventions conducted in Southeast Asia to inform about existing intervention designs and to derive sound evidence of their effectiveness. Our literature search results in 51 studies from five Southeast Asian countries from which we can extract 204 estimates. We sort the studies into six intervention categories and analyse them with respect to 23 different health and behavioural outcomes. While we find positive and significant average effects across all six types of interventions, we also document evidence of substantial publication bias. Using a meta-regression approach in which we correct for the publication bias, we instead fail to confirm positive average effects for some interventions. Especially dietary and physical activity interventions fail to achieve improvements in analysed health outcomes, while programs focusing on smoking cessation, on the take-up of preventive screening activities or educating patients on how to cope with NCDs achieve sizeable effects. We also present evidence that the size of the effect differs with the participants’ characteristics as well as with design features of the intervention. For local policymakers, the results provide important knowledge on how to address the increasing NCD burden in the coming years.
Mouse midbrain dopaminergic neurons survive loss of the PD-associated mitochondrial protein CHCHD2
Authors: Nguyen Mai K , McAvoy Kevin , Liao Szu-Chi , Doric Zak , Lo Iris , Li Huihui , Manfredi Giovanni , Nakamura Ken 
Published: November 2021

Abstract
Mutations in the mitochondrial protein CHCHD2 cause autosomal-dominant PD characterized by the preferential loss of substantia nigra dopamine (DA) neurons. Therefore, understanding the function of CHCHD2 in neurons may provide vital insights into how mitochondrial dysfunction contributes to neurodegeneration in PD. To investigate the normal requirement and function of CHCHD2 in neurons, we first examined CHCHD2 levels, and showed that DA neurons have higher CHCHD2 levels than other neuron types, both in vivo and in co-culture. We then generated mice with either a targeted deletion of CHCHD2 in DA neurons, or a deletion in the brain or total body. All three models were viable, and loss of CHCHD2 in the brain did not cause degeneration of DA neurons. Mice lacking CHCHD2 in DA neurons did display sex-specific changes to locomotor activity, but we did not observe differences in assays of muscle strength, exercise endurance, or motor coordination. Furthermore, mitochondria derived from mice lacking CHCHD2 did not display abnormalities in OXPHOS function. Lastly, resilience to CHCHD2 deletion could not be explained by functional complementation by its paralog CHCHD10, as deletion of both CHCHD10 and CHCHD2 did not cause degeneration of DA neurons in the midbrain. These findings support the hypothesis that pathogenic CHCHD2 mutations cause PD through a toxic gain-of-function, rather than loss-of-function mechanism.
Impact of fetal expression quantitative trait loci on transcriptome-wide association study of childhood leukemia
Authors: Yang Tianzhong , Mills Lauren J , Xue Haoran , Raduski Andrew , Williams Lindsay A , Spector Logan G 
Published: November 2021

Abstract
Transcriptome-wide association studies increase the yield of loci associated with disease phenotypes by focusing on expression quantitative trait loci (eQTL). The major source of eQTL data for is the Gene and Tissue Expression (GTEx) project, which is comprised entirely of adults, mainly those &gt;50 years of age at death. Since gene expression levels differ by developmental stage, it is not clear whether eQTLs derived from adult data sources are best suited for use in young-onset diseases such as pediatric cancers. To fill in this knowledge gap, we performed a large-scale eQTL mapping analysis in the GenCord study with newborn samples and compared it with GTEx. Under matched conditions, we found around 80% of the eQTLs in one study can be replicated in the other. However, among all eQTLs identified in GenCord (GTEx), 584 (1045) showed statistically significant differences in effect sizes in GTEx (GenCord). We further investigated how using fetal eQTL data can facilitate the genetic association study of acute lymphoblastic leukemia. GenCord and GTEx identified the same genetic loci with statistical significance; however, the overall association pattern was only weakly correlated. Our paper demonstrates age-differential eQTLs and shows their potential influence on childhood leukemia research.
Repetitive Transcranial Magnetic Stimulation for Generalized Anxiety Disorder: A Systematic Literature Review and Meta-Analysis
Authors: Parikh Tapan K , Strawn Jeffrey R , Walkup John T , Croarkin Paul E 
Published: November 2021

Abstract

Background
Anxiety disorders such as generalized anxiety disorder (GAD) impact 10% of the US population, and many patients do not completely respond to first-line treatments (e.g., selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and psychotherapy). Given the dearth of evidence for non-pharmacologic, non-psychotherapeutic interventions, we performed a systematic review and meta-analysis of repetitive transcranial magnetic stimulation (rTMS) in adults with GAD.

Methods
A systematic literature review using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted. Pre- and post-treatment anxiety scores were extracted, and a random-effects meta-analysis was conducted to determine the magnitude of improvement (standardized mean difference). Standard assessments of heterogeneity (e.g., Q-statistic, I2, and τ 2) and publication bias were performed.

Results
The initial search resulted in 3194 citations, of which 6 studies were included in the meta-analysis. In total, 152 patients were studied, including 97 patients who received active treatment and 55 who received sham treatment, and heterogeneity was modest (I2 13.32, Q = 5.77). In patients with GAD, rTMS produced a standardized mean difference of −1.857 (confidence interval: −2.219 to −1.494; P &lt; .001) with a prediction interval of −2.55 to −1.16.

Conclusions
The results suggest a robust effect of rTMS in GAD in the context of limited, heterogenous studies. Rigorously designed, randomized controlled trials of rTMS for GAD and related anxiety disorders are urgently needed. These studies will provide opportunities for biomarker development and integration of concurrent evidence-based psychotherapy to maximize results.
Behaviour of infinite chains described by Laurent operators: first/second-order equations
Authors: Liu Dongmei , Liu Liu , Lu Yufeng 
Published: November 2021

Abstract
This paper investigates the behaviour of infinite chains of kinematic points described by scalar Laurent operators with first/second-order linear differential equations. Some conditions on the initial states of these infinite chains are given to ensure that the corresponding solutions converge. In particular, a necessary and sufficient condition for the convergence of the first-order system is derived by using ergodic theory.
A hybrid Shewhart chart for visualizing and learning from epidemic data
Authors: Parry Gareth , Provost Lloyd p , Provost Shannon m , Little Kevin , Perla Rocco j 
Published: November 2021

Abstract

Objective
As the globe endures the coronavirus disease 2019 (COVID-19) pandemic, we developed a hybrid Shewhart chart to visualize and learn from day-to-day variation in a variety of epidemic measures over time.

Context
Countries and localities have reported daily data representing the progression of COVID-19 conditions and measures, with trajectories mapping along the classic epidemiological curve. Settings have experienced different patterns over time within the epidemic: pre-exponential growth, exponential growth, plateau or descent and/ or low counts after descent. Decision-makers need a reliable method for rapidly detecting transitions in epidemic measures, informing curtailment strategies and learning from actions taken.

Methods
We designed a hybrid Shewhart chart describing four ‘epochs’ ((i) pre-exponential growth, (ii) exponential growth, (iii) plateau or descent and (iv) stability after descent) of the COVID-19 epidemic that emerged by incorporating a C-chart and I-chart with a log-regression slope. We developed and tested the hybrid chart using international data at the country, regional and local levels with measures including cases, hospitalizations and deaths with guidance from local subject-matter experts.

Results
The hybrid chart effectively and rapidly signaled the occurrence of each of the four epochs. In the UK, a signal that COVID-19 deaths moved into exponential growth occurred on 17 September, 44 days prior to the announcement of a large-scale lockdown. In California, USA, signals detecting increases in COVID-19 cases at the county level were detected in December 2020 prior to statewide stay-at-home orders, with declines detected in the weeks following. In Ireland, in December 2020, the hybrid chart detected increases in COVID-19 cases, followed by hospitalizations, intensive care unit admissions and deaths. Following national restrictions in late December, a similar sequence of reductions in the measures was detected in January and February 2021.

Conclusions
The Shewhart hybrid chart is a valuable tool for rapidly generating learning from data in close to real time. When used by subject-matter experts, the chart can guide actionable policy and local decision-making earlier than when action is likely to be taken without it.
Bombs and Babies: Exposure to Terrorism and Fertility Choices in Nigeria
Authors: Rotondi Valentina , Rocca Michele 
Published: November 2021

AbstractThe aim of terrorism all over the world is to have fear rule over people’s lives. The consequences of terrorist attacks, however, are substantially different across contexts. In this paper we study the association between exposure to Boko Haram’s attacks and households’ fertility choices in Nigeria. We hypothesise that households exposed to terrorism increase their number of children as a way to insure against future unexpected shocks. We test this hypothesis using geolocalised panel data linked to information on terrorist attacks that occurred in the region. Consistent with our hypothesis, terrorism is found to increase fertility (proxied by the number of surviving children per household): a one standard deviation increase in the number of fatalities increases the probability that a household hit by terrorism has a newborn by $1\%$. This association is robust to the use of difference-in-differences and instrumental variables models—and therefore can be given a causal interpretation.
Space Suits and Gas Masks: Mary Ann Scherr and an Alternative View of Personal Technology
Authors: Perkov Kayleigh C 
Published: November 2021

Abstract
The development of commercial, wearable biosensors since the 1970s has been promoted as a rhetoric of optimization, in which one’s body can be improved through harnessing information. The wearable biosensor can therefore be understood as a tool of biomedicalization, in which patients are turned into consumers and health is a personal responsibility. This paper argues for a radical alternative vision of biosensors through an unexpected precursor, the American metalsmith Mary Ann Scherr (1921–2016). In the early 1970s Scherr debuted a series of ‘body monitoring’ jewellery. This jewellery responded both to a cybernetic notion of technological control as well a burgeoning ecological movement that positioned the body as porous—and therefore vulnerable—to its environment. A product of the studio craft and industrial design worlds, Scherr married function with a keen appreciation for adornment and sensuality. Scherr’s body monitors offer an alternative vision to the rhetoric of optimization, one that balances a desire for control through information with an emphasis on embodied form born through a sensual attention to physical experience.