bluuebunny/crossref_metadata_2025_split huggingface dataset:
DosEmi study protocol: a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of pharmacokinetic-guided reduced dosing compared with conventional dosing of emicizumab in people with haemophilia A
Authors: Donners Anouk , van der Zwet Konrad , Egberts Antoine C G , Fijnvandraat Karin , Mathôt Ron , Kruis Ilmar , Cnossen Marjon H , Schutgens Roger , Urbanus Rolf T , Fischer Kathelijn 
Published: June 2023

IntroductionEmicizumab effectively prevents bleeding in people with haemophilia A (PwHA), but is a burden for national healthcare budgets and consequently may limit access. According to the drug label, dosing of emicizumab is based on body weight with fixed intervals of 7, 14 or 28 days, which leads to mean plasma concentrations of 55 µg/mL (SD 15 µg/mL). However, a moderate variability of concentrations and a minimal effective concentration of 30 µg/mL have been suggested in studies. Therefore, a dose of emicizumab that targets a trough concentration of 30 µg/mL is hypothesised to be equally effective as conventional dosing in the prevention of bleeding.Methods and analysisWe designed a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of bleed control of ≥6 months on conventional dosing in comparison to ≥6 months on dose intervention. This dose intervention consists of reducing the dose of emicizumab to target a trough concentrations of 30 µg/mL using individual pharmacokinetic (PK) parameters. Ninety-five PwHA aged >1 years who received conventional dosing of emicizumab for ≥12 months with good bleeding control during the last 6 months will be recruited from all Dutch haemophilia treatment centres. The study is powered to detect a clinically relevant decrease (risk difference) of 15% in the proportion of patients without treated bleeds during follow-up. Secondary endpoints are spontaneous joint or muscle bleeds, and annualised treated bleeding rates (using negative binomial regression). Cost-effectivity between conventional dosing and individualised PK-guided dosing of emicizumab will be compared.Ethics and disseminationThe DosEmi study was approved by the Medical Ethics Review Committee NedMec of the University Medical Center of Utrecht, The Netherlands. Study results will be communicated through publications in international scientific journals and presentations at (inter)national conferences.Trial registration numberEUCTR2021-004039-10-NL athttps://trialsearch.who.int.Protocol versionV.4.1 on 28 October 2022 (DosEmi protocol_V4.1; NL81112.041.22).
Codesigning a user-centred digital psychoeducational tool for youth mental well-being with families in Canada: study protocol for a sequential exploratory mixed methods study
Authors: Moss Stephana Julia , Racine Nicole , Ahmed Sofia , Birnie Kathryn , Cherak Michal S , Curran Janet A , Halperin Donna , Halperin Scott A , Harley Micaela , Hu Jia , Leppan Laura , Nickel Angie , Russell Kristine , Solis May , Smith Stacie , Soo Andrea , Stelfox Maia , Tutelman Perri R , Stelfox Henry Thomas , Fiest Kirsten M , Parsons Leigh Jeanna 
Published: June 2023

IntroductionOn 11 March 2020, WHO declared the novel coronavirus (COVID-19) disease a global pandemic. Governments globally implemented physical distancing measures and closure of public institutions that resulted in varying implications to youth mental well-being (eg, social isolation, reduced extracurricular activities). These impacts may have detrimental short-term and long-term effects on youth mental well-being; care for youth with mental health disorders was already overstretched, underfunded and fragmented before the pandemic and youth are not often considered in mental health initiatives. There is a pressing need to partner with youth and families to target and improve youth mental well-being prior to the onset of a mental health disorder, as well as to conduct research on youth mental well-being needs related to pandemic recovery. Here we present a protocol for partnering with youth and families to codesign a user-centred digital tool for youth mental well-being.Methods and analysisWe will conduct a national research study to develop a catalogue of recommendations specific to supporting youth mental well-being, and a digital tool to support youth mental well-being through three phases of work: (1) expert consultation on data related to supporting youth mental well-being existing within our Pandemic Preparedness Research Program; (2) codesign of an innovative digital tool for youth mental well-being; and (3) assessment of the tool’s usability and acceptability.Ethics and disseminationThis study has been approved by the Dalhousie Research Ethics Board (2023-6538) and the Conjoint Health Research Ethics Board (23-0039). This study will complement ongoing foundational research in youth conducted by our team that involves partnering with youth and families to understand the unique implications of the pandemic on this population.
On testing proportional odds assumptions for proportional odds models
Authors: Liu Anqi , He Hua , Tu Xin M , Tang Wan 
Published: June 2023

Proportional odds models are commonly used to model ordinal responses, but the proportional odds assumption may not hold in practice, leading to biased inference. Tests such as score, Wald and likelihood ratio (LR) have been proposed to evaluate the proportional odds assumption based on models without the assumption. Brant has proposed an independent binary model-based Wald-type test, and Wolfe and Gould have extended the idea to propose an LR-type test.This paper provides a brief review of the Brant and Wolfe-Gould tests for evaluating the proportional odds assumption and evaluates their performance through simulation studies and a real data example. Sample programs are provided in SAS, SPSS and Stata to facilitate the implementation of these tests using standard statistical software packages.This study highlights the importance of evaluating the proportional odds assumption when using proportional odds models for ordinal responses. The sample programs provided in this paper make it easy for researchers to apply these tests in their own analyses using standard statistical software packages.
Impact of built environment change on all-cause and cause-specific mortality: a novel longitudinal method and study
Authors: Macdonald Laura , Nicholls Natalie , Brown Denise , Mitchell Richard 
Published: June 2023

BackgroundPublic health research increasingly acknowledges the influence of built environments (BE) on health; however, it is uncertain how BE change is associated with better population health and whether BE change can help narrow health inequalities. This knowledge gap is partly due to a lack of suitable longitudinal BE data in most countries. We devised a method to quantify BE change longitudinally and explored associations with mortality. The method is replicable in any nation that captures BE vector map data.MethodsOrdnance Survey data were used to categorise small areas as having no change, loss or gain, in buildings, roads, and woodland between 2015 and 2019. We examined individual mortality records for 2012–2015 and 2016–2019, using negative binomial regression to explore associations between BE change and all-cause and cause-specific mortality, adjusting for income deprivation.ResultsBE change varied significantly by deprivation and urbanicity. Change in the BE and change in mortality were not related, however, areas that went on to experience BE change had different baseline mortality rates compared with those that did not. For example, areas that gained infrastructure already had lower mortality rates.ConclusionWe provide new methodology to quantify BE change over time across a nation. Findings provide insight into the health of areas that do/do not experience change, prompting critical perspectives on cross-sectional studies of associations between BE and health. Methods and findings applied internationally could explore the context of BE change and its potential to improve health in areas most in need beyond the UK.
Tobacco exposure primes the secretion of CCL21 positively associated with tertiary lymphoid structure and response to immunotherapy
Authors: Yin Xuewen , Wang Hui , Li Rutao , Song Xuming , Zhang Te , Liang Yingkuan , Chen Yu-Zhong , Yu Xinnian , Mao Qixing , Xia Wenjie , Chen Bing , Xu Lin , Dong Gaochao , Jiang Feng 
Published: June 2023

BackgroundIt has been reported that smoking history as a predictor of immunotherapy efficacy in patients with advanced lung cancer, however, the underlying mechanisms of this phenomenon remain largely unknown.MethodsThe patients with lung adenocarcinoma’s (LUAD) cohort and the orthotopical transplanted mouse model were used to explore the correlation between smoking status and tertiary lymphoid structure (TLS) and chemokine CCL21, respectively. Cell adhesion and co-immunoprecipitation assays were performed to explore the interaction between CD4+T cells and CD20+B cells under tobacco exposure. Chromatin immunoprecipitation-PCR was used to dissect the mechanism of upregulated CCL21 secretion in tobacco treatment. Serum CCL21 level was recorded in patients with LUAD treated with immunotherapy.ResultsHere we observed that individuals with a smoking history exhibit an increased quantity and maturation level of TLS compared with non-smokers, along with higher levels of CCL21 secretion. Tobacco exposure promoted CCL21 expression in an epithelial cell-intrinsic manner, of which BaP, the main component of tobacco, facilitated the nuclear retention of the aryl hydrocarbon receptor that occupied the promoter of CCL21. Additionally, the activated CCL21/CCR7 axis increased the CD11a expression of CD4+T cells, boosting the interaction with CD20+B cells dependent on ICAM1, which potentially induced the TLSs formation. Patients with elevated serum levels of CCL21 benefited more from immunotherapy.ConclusionsPatients with a smoking history exhibited higher levels of TLS via the CCL21-dependent mechanism, serum CCL21 was identified as a reliable biomarker for predicting the efficacy of immunotherapy.
Batching of Tasks by Users of Pseudonymous Forums: Anonymity Compromise and Protection
Authors: Goldberg Alexander , Fanti Giulia , Shah Nihar B. 
Published: June 2023

In a number of applications where anonymity is critical, users act under pseudonyms to preserve their privacy. For instance, in scientific peer review using forums like OpenReview.net, reviewers make comments on papers that are publicly viewable. Reviewers who have been assigned multiple papers operate under different pseudonyms across their papers to remain anonymous. Other examples of publicly visible tasks where users operate under pseudonyms include Wikipedia editing and cryptocurrency transactions.
In these settings, it is common for users to engage in batching - the completion of several similar tasks at the same time. Batching occurs both due to natural bursts in activity (e.g., a person visits a website and makes many comments at once) or as a productivity strategy used to streamline work.
In peer-review forums such as computer science conferences, reviewers and meta-reviewers are often assigned multiple papers. We find empirically that reviewers are highly likely to batch their comments and/or reviews across papers. In analysis of data from a top Computer Science conference with thousands of papers, reviewers, and discussion comments we find that when reviewers and meta-reviewers comment on multiple papers, they have a 30.10% chance of batching their comments within 5 minutes of one other. In comparison, any randomly chosen pair of reviewers and meta- reviewers had only a 0.66% chance of making comments on different papers within 5 minutes of each other.
Duo: A High-Throughput Reconfigurable Datacenter Network Using Local Routing and Control
Authors: Zerwas Johannes , Györgyi Csaba , Blenk Andreas , Schmid Stefan , Avin Chen 
Published: June 2023

The performance of many cloud-based applications critically depends on the capacity of the underlying datacenter network. A particularly innovative approach to improve the throughput in datacenters is enabled by emerging optical technologies, which allow to dynamically adjust the physical network topology, both in an oblivious or demand-aware manner. However, such topology engineering, i.e., the operation and control of dynamic datacenter networks, is considered complex and currently comes with restrictions and overheads.
We present Duo, a novel demand-aware reconfigurable rack-to-rack datacenter network design realized with a simple and efficient control plane. Duo is based on the well-known de Bruijn topology (implemented using a small number of optical circuit switches) and the key observation that this topology can be enhanced using dynamic ("opportunistic") links between its nodes.
In contrast to previous systems, Duo has several desired features: i) It makes effective use of the network capacity by supporting integrated and multi-hop routing (paths that combine both static and dynamic links). ii) It uses a work-conserving queue scheduling which enables out-of-the-box TCP support. iii) Duo employs greedy routing that is implemented using standard IP longest prefix match with small forwarding tables. And iv) during topological reconfigurations, routing tables require only local updates, making this approach ideal for dynamic networks.
We evaluate Duo in end-to-end packet-level simulations, comparing it to the state-of-the-art static and dynamic networks designs. We show that Duo provides higher throughput, shorter paths, lower flow completion times for high priority flows, and minimal packet reordering, all using existing network and transport layer protocols. We also report on a proof-of-concept implementation of \system's control and data plane.
Fiat Lux: Illuminating IPv6 Apportionment with Different Datasets
Authors: Hsu Amanda , Li Frank , Pearce Paul 
Published: June 2023

IPv6 adoption continues to grow, making up more than 40% of client traffic to Google globally. While the ubiquity of the IPv4 address space makes it comparably easier to understand, the vast and less studied IPv6 address space motivates a variety of works detailing methodology to collect and analyze IPv6 properties, many of which use knowledge from specific data sources as a lens for answering research questions. Despite such work, questions remain on basic properties such as the appropriate prefix size for research tasks.
Our work fills this knowledge gap by presenting an analysis of the apportionment of the IPv6 address space from the ground-up, using data and knowledge from numerous data sources simultaneously, aimed at identifying how to leverage IPv6 address information for a variety of research tasks. Utilizing WHOIS data from RIRs, routing data, and hitlists, we highlight fundamental differences in apportionment sizes and structural properties depending on data source and examination method. We focus on the different perspectives each dataset offers and the disjoint, heterogeneous nature of these datasets when taken together. We additionally leverage a graph-based analysis method for these datasets that allows us to draw conclusions regarding when and how to intersect the datasets and their utility. The differences in each dataset's perspective is not due to dataset problems but rather stems from a variety of differing structural and deployment behaviors across RIRs and IPv6 providers alike. In light of these inconsistencies, we discuss network address partitioning, best practices, and considerations for future IPv6 measurement and analysis projects.
Joint Learning and Control in Stochastic Queueing Networks with Unknown Utilities
Authors: Fu Xinzhe , Modiano Eytan 
Published: June 2023

We study the optimal control problem in stochastic queueing networks with a set of job dispatchers connected to a set of parallel servers with queues. Jobs arrive at the dispatchers and get routed to the servers following some routing policy. The arrival processes of jobs and the service processes of servers are stochastic with unknown arrival rates and service rates. Upon the completion of each job from dispatcher un at server sm, a random utility whose mean is unknown is obtained. We seek to design a control policy that makes routing decisions at the dispatchers and scheduling decisions at the servers to maximize the total utility obtained by the end of a finite time horizon T. The performance of policies is measured by regret, which is defined as the difference in total expected utility with respect to the optimal dynamic policy that has access to arrival rates, service rates and underlying utilities.
We first show that the expected utility of the optimal dynamic policy is upper bounded by T times the solution to a static linear program, where the optimization variables correspond to rates of jobs from dispatchers to servers and the feasibility region is parameterized by arrival rates and service rates. We next propose a policy for the optimal control problem that is an integration of a learning algorithm and a control policy. The learning algorithm seeks to learn the optimal extreme point solution to the static linear program based on the information available in the optimal control problem. The control policy, a mixture of priority-based and Joint-the-Shortest-Queue routing at the dispatchers and priority-based scheduling at the servers, makes decisions based on the graphical structure induced by the extreme point solutions provided by the learning algorithm. We prove that our policy achieves logarithmic regret whereas application of existing techniques to the optimal control problem would lead to Ω(√T)-regret. The theoretical analysis is further complemented with simulations to evaluate the empirical performance of our policy.
JS Capsules: A Framework for Capturing Fine-grained JavaScript Memory Measurements for the Mobile Web.
Authors: Naseer Usama , Benson Theophilus A. 
Published: June 2023

Understanding the resource consumption of the mobile web is an important topic that has garnered much attention in recent years. However, existing works mostly focus on the networking or computational aspects of the mobile web and largely ignore memory, which is an important aspect given the mobile web's reliance on resource-heavy JavaScript.
In this paper, we propose a framework, called JS Capsule, for characterizing the memory of JavaScript functions and, using this framework, we investigate the key browser mechanics that contribute to the memory overhead. Leveraging our framework on a testbed of Android mobile phones, we conduct measurements of the Alexa top 1K websites. While most existing frameworks focus on V8 --- the JavaScript engine used in most popular browsers --- in the context of memory, our measurements show that the memory implications of JavaScript extends far beyond V8 due to the cascading effects that certain JavaScript calls have on the browser's rendering mechanics. We quantify and highlight the direct impact that website DOM have on JavaScript memory overhead and present, to our knowledge, the first root-cause analysis to dissect and characterize their impact on JavaScript memory overheads.
Mars: Near-Optimal Throughput with Shallow Buffers in Reconfigurable Datacenter Networks
Authors: Addanki Vamsi , Avin Chen , Schmid Stefan 
Published: June 2023

The performance of large-scale computing systems often critically depends on high-performance communication networks. Dynamically reconfigurable topologies, e.g., based on optical circuit switches, are emerging as an innovative new technology to deal with the explosive growth of datacenter traffic. Specifically, periodic reconfigurable datacenter networks (RDCNs) such as RotorNet (SIGCOMM 2017), Opera (NSDI 2020) and Sirius (SIGCOMM 2020) have been shown to provide high throughput, by emulating a complete graph through fast periodic circuit switch scheduling.
However, to achieve such a high throughput, existing reconfigurable network designs pay a high price: in terms of potentially high delays, but also, as we show as a first contribution in this paper, in terms of the high buffer requirements. In particular, we show that under buffer constraints, emulating the high-throughput complete graph is infeasible at scale, and we uncover a spectrum of unvisited and attractive alternative RDCNs, which emulate regular graphs, but with lower node degree than the complete graph.
We present Mars, a periodic reconfigurable topology which emulates a d-regular graph with near-optimal throughput. In particular, we systematically analyze how the degree~d can be optimized for throughput given the available buffer and delay tolerance of the datacenter. We further show empirically that Mars achieves higher throughput compared to existing systems when buffer sizes are bounded.
The M/M/k with Deterministic Setup Times
Authors: Williams Jalani K. , Harchol-Balter Mor , Wang Weina 
Published: June 2023

Capacity management, whether it involves servers in a data center, or human staff in a call center, or doctors in a hospital, is largely about balancing a resource-delay tradeoff. On the one hand, one would like to turn off servers when not in use (or send home staff that are idle) to save on resources. On the other hand, one wants to avoid the considerable setup time required to turn an off server back on. This paper aims to understand the delay component of this tradeoff, namely, what is the effect of setup time on average delay in a multi-server system?
Surprisingly little is known about the effect of setup times on delay. While there has been some work on studying the M/M/k with Exponentially-distributed setup times, these works provide only iterative methods for computing mean delay, giving little insight as to how delay is affected by k, by load, and by the setup time. Furthermore, setup time in practice is much better modeled by a Deterministic random variable, and, as this paper shows, the effect of a Deterministic setup time is nothing like that of an Exponentially-distributed setup time.
This paper provides the first analysis of the M/M/k with Deterministic setup times. We prove a lower bound on the effect of setup on delay. Our result is a simple algebraic formula which provides insight into how delay scales with the input parameters. For more details, see the full paper.