bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment allocation strategies for umbrella trials in the presence of multiple biomarkers: A comparison of methods
Authors: Ouma Luke Ondijo , Grayling Michael J. , Zheng Haiyan , Wason James 
Published: March 2021

AbstractUmbrella trials are an innovative trial design where different treatments are matched with subtypes of a disease, with the matching typically based on a set of biomarkers. Consequently, when patients can be positive for more than one biomarker, they may be eligible for multiple treatment arms. In practice, different approaches could be applied to allocate patients who are positive for multiple biomarkers to treatments. However, to date there has been little exploration of how these approaches compare statistically. We conduct a simulation study to compare five approaches to handling treatment allocation in the presence of multiple biomarkers – equal randomisation; randomisation with fixed probability of allocation to control; Bayesian adaptive randomisation (BAR); constrained randomisation; and hierarchy of biomarkers. We evaluate these approaches under different scenarios in the context of a hypothetical phase II biomarker‐guided umbrella trial. We define the pairings representing the pre‐trial expectations on efficacy as linked pairs, and the other biomarker‐treatment pairings as unlinked. The hierarchy and BAR approaches have the highest power to detect a treatment‐biomarker linked interaction. However, the hierarchy procedure performs poorly if the pre‐specified treatment‐biomarker pairings are incorrect. The BAR method allocates a higher proportion of patients who are positive for multiple biomarkers to promising treatments when an unlinked interaction is present. In most scenarios, the constrained randomisation approach best balances allocation to all treatment arms. Pre‐specification of an approach to deal with treatment allocation in the presence of multiple biomarkers is important, especially when overlapping subgroups are likely.
Reliability analysis of the dynamic system for the Chen model through sequential order statistics
Authors: Tyagi Abhishek , Choudhary Neha , Singh Bhupendra 
Published: March 2021

AbstractRecently, the two‐parameter Chen distribution has widely been used for reliability studies in various engineering fields. In this article, we have developed various statistical inferences on the composite dynamic system, assuming Chen distribution as a baseline model. In this dynamic system, failure of a component induces a higher load on the surviving components and thus increases component hazard rate through a power‐trend process. The classical and Bayesian point estimates of the unknown parameters of the composite system are obtained by the method of maximum likelihood and Markov chain Monte Carlo techniques, respectively. In the Bayesian framework, we have used gamma priors to obtain Bayes estimates of unknown parameters under the squared error and generalized entropy loss functions. The interval estimates of the baseline reliability function are obtained by using the Fisher information matrix and Bayesian method. A parametric hypothesis test is presented to test whether the failed components change the hazard rate function. A compact simulation study is carried out to examine the behavior of the proposed estimation methods. Finally, one real data analysis is performed for illustrative purposes.
Finite‐time adaptive neural control for nonlinear systems under state‐dependent sensor attacks
Authors: Lv Wenshun 
Published: March 2021

AbstractThis article proposes a finite‐time control scheme for a class of uncertain nonlinear systems in the presence of sensor attacks. Specifically, based on the backstepping technology and the nonlinear function approximation capability of radial basis function neural networks, we develop an adaptive controller, guaranteeing the finite‐time stability of the closed‐loop system despite sensor attacks. In particular, the unknown time‐varying state‐feedback gains caused by sensor attacks are handled by Nussbaum functions. To decrease the design difficulty of the finite‐time controller, a novel practical finite‐time stability criterion is given. Finally, two simulation examples are provided, demonstrating the effectiveness of the proposed adaptive control scheme.
Transborder Gene Flow between Canada and the USA and Fine‐Scale Population Structure of Atlantic Cod in the Broader Gulf of Maine Region
Authors: Puncher Gregory Neils , Wang Yanjun , Martin Ryan , DeCelles Gregory , Cadrin Steven X. , Zemeckis Douglas , Rowe Sherrylynn , Leblanc Nathalie M. , Parent Genevieve J. , Pavey Scott A. 
Published: March 2021

AbstractFishery managers have struggled for decades to rebuild stocks of Atlantic Cod Gadus morhua in the northwestern Atlantic Ocean, and the resolution of current fine‐scale population structure will surely help those efforts. Using double digest restriction‐site associated DNA sequencing, we analyzed 248 adult and 215 juvenile Atlantic Cod collected from areas bordering the Canada–USA boundary in 2017–2018. Chromosomal inversions from linkage group (LG) 2 and LG 7 contribute the largest amount of variance to the data set. A southwesterly decrease in the proportion of LG 1 inversion haplotypes may indicate gene flow from areas north of 45°N. Samples from both the northern Gulf of Maine and Bay of Fundy were genetically distinct from all other samples, suggesting that local spawning groups may still be active. Genetic similarities between Atlantic Cod from Browns Bank and eastern Georges Bank indicate that transborder gene flow is ongoing. These results will help to better define the stocks in order to guide the implementation of management strategies in the USA and Canada, which should consider rebuilding exhausted and genetically isolated populations.
Anodic Oxidation of Phenols: A Key Step for the Synthesis of Natural Products
Authors: Yamamoto Takashi , Saitoh Tsuyoshi , Einaga Yasuaki , Nishiyama Shigeru 
Published: March 2021

AbstractNatural products have played a significant role not only in discovery of drugs but also in development of organic chemistry by providing the synthetic challenges. Inspired by biosynthesis where enzymes catalyze a multi‐step reaction, we have investigated the natural product synthesis utilizing electrochemical reactions as the key step. Electrochemical organic synthesis, so‐called electro‐organic synthesis, enables to control the reactivity of substrates simply by tuning electrolysis conditions. In this Personal Account, we overview the recent progress of our research projects about natural product synthesis, in which anodic oxidation of phenol compounds affords the important frameworks such as diaryl ether, spirodienone, and spiroisoxazoline.
Investigation of Cyclam Based Re‐Complexes as Potential Electrocatalysts for the CO2Reduction Reaction
Authors: Gerschel Philipp , Cordes Anna L. , Bimmermann Sarah , Siegmund Daniel , Metzler‐Nolte Nils , Apfel Ulf‐Peter 
Published: March 2021

AbstractAmong the various homogenous electrocatalysts, especially Re(bpy)(CO)3Cl and [Ni(cyclam)]2+were shown to be highly efficient for the selective conversion of CO2to CO at moderate potentials. However, a purposeful combination of a ReItricarbonyl unit with a cyclam ligand hitherto received no attention. Herein, we report on a series of cyclam based Re complexes comprising the original {N4} as well as heteroatom‐altered ligand frameworks, describe their synthesis, reveal their coordination behavior and furthermore investigate their performance towards the electrochemical CO2reduction.
From $$ \mathcal{N} $$ = 4 Super-Yang-Mills on ℝℙ4 to bosonic Yang-Mills on ℝℙ2
Authors: Wang Yifan 
Published: March 2021

Abstract
We study the four-dimensional $$ \mathcal{N} $$
N
= 4 super-Yang-Mills (SYM) theory on the unorientable spacetime manifold ℝℙ4. Using supersymmetric localization, we find that for a large class of local and extended SYM observables preserving a common supercharge $$ \mathcal{Q} $$
Q
, their expectation values are captured by an effective two-dimensional bosonic Yang-Mills (YM) theory on an ℝℙ2 submanifold. This paves the way for understanding $$ \mathcal{N} $$
N
= 4 SYM on ℝℙ4 using known results of YM on ℝℙ2. As an illustration, we derive a matrix integral form of the SYM partition function on ℝℙ4 which, when decomposed into discrete holonomy sectors, contains subtle phase factors due to the nontrivial η-invariant of the Dirac operator on ℝℙ4. We also comment on potential applications of our setup for AGT correspondence, integrability and bulk-reconstruction in AdS/CFT that involve cross-cap states on the boundary.
Light rings of five-dimensional geometries
Authors: Bianchi M. , Consoli D. , Grillo A. , Morales J. F. 
Published: March 2021

Abstract
We study massless geodesics near the photon-spheres of a large family of solutions of Einstein-Maxwell theory in five dimensions, including BHs, naked singularities and smooth horizon-less JMaRT geometries obtained as six-dimensional uplifts of the five-dimensional solution. We find that a light ring of unstable photon orbits surrounding the mass center is always present, independently of the existence of a horizon or singularity. We compute the Lyapunov exponent, characterizing the chaotic behaviour of geodesics near the ‘photon-sphere’ and the time decay of ring-down modes dominating the response of the geometry to perturbations at late times. We show that, for geometries free of naked singularities, the Lyapunov exponent is always bounded by its value for a Schwarzschild BH of the same mass.
QNEC2 in deformed holographic CFTs
Authors: Ecker C. , Grumiller D. , Soltanpanahi H. , Stanzer P. 
Published: March 2021

AbstractWe use the quantum null energy condition in strongly coupled two-dimensional field theories (QNEC2) as diagnostic tool to study a variety of phase structures, including crossover, second and first order phase transitions. We find a universal QNEC2constraint for first order phase transitions with kinked entanglement entropy and discuss in general the relation between the QNEC2-inequality and monotonicity of the Casini-Huertac-function. We then focus on a specific example, the holographic dual of which is modelled by three-dimensional Einstein gravity plus a massive scalar field with one free parameter in the self-interaction potential. We study translation invariant stationary states dual to domain walls and black branes. Depending on the value of the free parameter we find crossover, second and first order phase transitions between such states, and thec-function either flows to zero or to a finite value in the infrared. We present evidence that evaluating QNEC2for ground state solutions allows to predict the existence of phase transitions at finite temperature.
Mixed EW-QCD leading fermionic three-loop corrections at $$ \mathcal{O} $$(αsα2) to electroweak precision observables
Authors: Chen Lisong , Freitas Ayres 
Published: March 2021

Abstract
Measurements of electroweak precision observables at future electron-position colliders, such as the CEPC, FCC-ee, and ILC, will be sensitive to physics at multi-TeV scales. To achieve this sensitivity, precise predictions for the Standard Model expectations of these observables are needed, including corrections at the three- and four-loop level. In this article, results are presented for the calculation of a subset of three-loop mixed electroweak-QCD corrections, stemming from diagrams with a gluon exchange and two closed fermion loops. The numerical impact of these corrections is illustrated for a number of applications: the prediction of the W-boson mass from the Fermi constant, the effective weak mixing angle, and the partial and total widths of the Z boson. Two alternative renormalization schemes for the top-quark mass are considered, on-shell and $$ \overline{\mathrm{MS}} $$

MS
¯

.
Holographic KMS relations at finite density
Authors: Loganayagam R. , Ray Krishnendu , Sharma Shivam K. , Sivakumar Akhil 
Published: March 2021

Abstract
We extend the holographic Schwinger-Keldysh prescription introduced in [1] to charged black branes, with a view towards studying Hawking radiation in these backgrounds. Equivalently we study the real time fluctuations of the dual CFT held at finite temperature and finite chemical potential. We check our prescription using charged Dirac probe fields. We solve the Dirac equation in a boundary derivative expansion extending the results in [2]. The Schwinger-Keldysh correlators derived using this prescription automatically satisfy the appropriate KMS relations with Fermi-Dirac factors.
Word vector embeddings hold social ontological relations capable of reflecting meaningful fairness assessments
Authors: Izzidien Ahmed 
Published: March 2021

AbstractProgramming artificial intelligence (AI) to make fairness assessments of texts through top-down rules, bottom-up training, or hybrid approaches, has presented the challenge of defining cross-cultural fairness. In this paper a simple method is presented which uses vectors to discover if a verb is unfair (e.g., slur, insult) or fair (e.g., thank, appreciate). It uses already existing relational social ontologies inherent in Word Embeddings and thus requires no training. The plausibility of the approach rests on two premises. That individuals consider fair acts those that they would be willing to accept if done to themselves. Secondly, that such a construal is ontologically reflected in Word Embeddings, by virtue of their ability to reflect the dimensions of such a perception. These dimensions being: responsibility vs. irresponsibility, gain vs. loss, reward vs. sanction, joy vs. pain, all as a single vector (FairVec). The paper finds it possible to quantify and qualify a verb as fair or unfair by calculating the cosine similarity of the said verb’s embedding vector against FairVec—which represents the above dimensions. We apply this to Glove and Word2Vec embeddings. Testing on a list of verbs produces an F1 score of 95.7, which is improved to 97.0. Lastly, a demonstration of the method’s applicability to sentence measurement is carried out.
Routine postoperative blood tests fail to reliably predict procedure-related complications after laparoscopic cholecystectomy
Authors: Strohäker Jens , Wiegand Lisa , Beltzer Christian , Königsrainer Alfred , Ladurner Ruth , Bachmann Robert 
Published: March 2021

AbstractPurposeLaparoscopic cholecystectomy is a highly standardized surgical procedure with a low risk of complications. However, once complications develop, they can be life-threatening. The aim of this study was to evaluate the value of blood tests on postoperative day one regarding their potential to predict postoperative complicationsMethodsA cohort study of 1706 consecutive cholecystectomies performed at a tertiary hospital and teaching facility over a 5-year period between 2014 and 2019.ResultsPatients that had open CCE or conversion CCE were excluded. One thousand five hundred eighty-six patients were included in the final analysis that received a laparoscopic cholecystectomy (CCE). One thousand five hundred twenty-three patients had blood tests on POD 1. Forty-one complications were detected including 14 bile leaks, 2 common bile duct injuries, 13 choledocholithiasis, 9 hematomas, and 2 active bleedings. Bilirubin was elevated in 351 patients on POD 1. A drop of more than 3 mg/dl of hemoglobin was reported in 39 patients. GPT was elevated 3 × above the upper limit in 102 patients. All three tests showed a low sensitivity and specificity in detecting postoperative complications.ConclusionsEarly postoperative blood tests alone show a low specificity in detecting postoperative complications after laparoscopic CCE. Their main benefit appears to be the negative predictive value, when they are normal. Routine blood testing appears to be unnecessary and should be based on the intraoperative diagnosis and postoperative clinical findings.
Laparoscopic hand-sewn cardioplasty: an alternative procedure for end-stage achalasia
Authors: Senra Fátima , Navaratne Lalin , Acosta-Mérida Asunción , Gould Stuart , Martínez-Isla Alberto 
Published: March 2021

Abstract
Background
Primary achalasia is a rare oesophageal motor disorder characterized by the absence of swallow-induced relaxation of the lower oesophageal sphincter and diminished or absent oesophageal body peristalsis. Around 5% of these patients will develop end-stage achalasia, where oesophagectomy may be advocated. We present the laparoscopic hand-sewn cardioplasty as an alternative ‘oesophagus-preserving’ procedure in patients with end-stage achalasia.

Methods
We present a retrospective review of four patients who underwent laparoscopic hand-sewn cardioplasty. Data collected included pre-operative demographic information and investigations; and post-operative outcomes. Patients were scored pre- and post-operatively using Reflux Symptom Index, Eating Assessment Tool-10 and Voice Handicap Index-10 questionnaires.

Results
Four patients underwent laparoscopic hand-sewn cardioplasty during the study period. In one patient, it was performed as a rescue procedure during attempted myotomy following multiple perforations of friable mucosa. In the other three patients, laparoscopic hand-sewn cardioplasty was performed for end-stage achalasia. None of the patients had post-operative complications and all patients were discharged on the second post-operative day. All patients experienced improvement in swallowing symptoms (EAT-10; p = 0.03) but developed post-operative gastroesophageal reflux.

Conclusion
To our knowledge, this is the first published case series of laparoscopic hand-sewn cardioplasty for end-stage achalasia. It appears to be a safe and effective procedure for the treatment of end-stage achalasia, offering an alternative minimally invasive procedure to oesophagectomy. Laparoscopic hand-sewn cardioplasty can also be used as a ‘rescue’ procedure during myotomy in patients who have poor-quality mucosa which perforates intra-operatively or is at high risk of perforation/leaking post-operatively.
Antihormone treatment differentially regulates PSA secretion, PSMA expression and 68Ga–PSMA uptake in LNCaP cells
Authors: Mathy C. S. , Mayr T. , Kürpig S. , Meisenheimer M. , Dolscheid-Pommerich R. C. , Stoffel-Wagner B. , Kristiansen G. , Essler M. , Muders M. H. , Bundschuh R. A. 
Published: March 2021

Abstract
Background
In recent years, a variety of innovative therapeutics for castration-resistant prostate cancer have been developed, including novel anti-androgenic drugs, such as abiraterone or VPC-13566. Therapeutic monitoring of these pharmaceuticals is performed either by measuring PSA levels in serum or by imaging. PET using PSMA ligands labeled with Fluor-18 or Gallium-68 is the most sensitive and specific imaging modality for detection of metastases in advanced prostate cancer. To date, it remains unclear how PSMA expression is modulated by anti-hormonal treatment and how it correlates with PSA secretion.

Methods
We analyzed modulation of PSMA-mRNA and protein expression, 68Ga–PSMA uptake and regulation of PSA secretion by abiraterone or VPC-13566 in LNCaP cells in vitro.

Results
We found that abiraterone and VPC-13566 upregulate PSMA protein and mRNA expression but block PSA secretion in LNCaP cells. Both anti-androgens also enhanced 68Ga–PSMA uptake normalized by the number of cells, whereas abiraterone and VPC-13566 reduced 68Ga–PSMA uptake in total LNCaP monolayers treated due to cell death.

Conclusion
Our data indicate that PSA secretion and PSMA expression are differentially regulated upon anti-androgen treatment. This finding might be important for the interpretation of 68Ga–PSMA PET images in monitoring therapies with abiraterone and VPC-13566 in prostate cancer patients, but needs to be validated in vivo.
Historical reconfigurations of a social–ecological system adapting to economic, policy and climate changes in the French Alps
Authors: Bruley Enora , Locatelli Bruno , Vendel François , Bergeret Agnès , Elleaume Nicolas , Grosinger Julia , Lavorel Sandra 
Published: March 2021

AbstractTo ensure their quality of life, people adapt to multiple changes by maintaining or transforming the structure and functions of their socio-ecological systems (SES). A better understanding of mechanisms underpinning SES adaptation, especially the contribution of changes in human–nature interactions, is crucial to facilitate adaptation to future challenges. Using a chronosystemic timeline and based on literature, archives and local knowledge of inhabitants, we explored the past trajectory of a mountain SES (Pays de la Meije, French Alps) since 1900 by analysing drivers, impacts and responses. We hypothesised that adaptation has occurred through changes in the co-production of nature’s contributions to people (NCP). We identified four historical periods of combined changes in agriculture and tourism with associated changes in NCP. Results show which and how drivers of changes have influenced NCP co-production, how NCP have been mobilised in adaptive responses and how human and natural capitals involved in NCP co-production have been reconfigured for adaptation. We show that drivers of change have been mainly exogenous and out of the control of local actors, like public policies, markets and consumption patterns. These drivers can directly impact the capitals involved in NCP co-production like amount of workforce, knowledge or skills, creating not only threats but also opportunities for the livelihood of the local community. Depending on the intensity of capital reconfiguration and the type of NCP involved, adaptive responses range from resistance to transformation of the governance system and socio-economic sectors. This analysis highlights existing path dependencies that could hinder future adaptation.
Sauerbruch, STARPAHC, and SARS: Historical Perspectives on Readiness and Barriers in Telemedicine
Authors: Reifegerste Doreen , Harst Lorenz , Otto Lena 
Published: March 2021

Abstract
Aim
Telemedicine is a promising solution to extend traditional health care services. Even though mainly discussed during the past two decades, its roots go back into the past century and even further, considering the use of bonfires to warn other villages of diseases. Insights from historical cases can therefore be useful for the ongoing discussion regarding the successful implementation of telemedicine.

Subject and Methods
We analyzed three historical telemedicine cases (varying regarding time and place) and extracted their success factors and barriers as well as assessed their maturity by using the Telemedicine Community Readiness Model (TCRM). Evidence-based categories of success factors and barriers as well as the TCRM’s dimensions were used as deductive categories to analyze the study material’s content.

Results
The analysis showed that the readiness for telemedicine is higher when the technology is the only option to access health care services. In all three cases, core readiness played a central role. However, the health sector, existing technology, and finance were barriers present at all times, while during pandemics, some barriers are only temporarily removed, for example, by putting legal issues on hold. The analyzed cases were all on lower levels of maturity as they mainly represent pilot tests or exceptional circumstances.

Conclusion
Results indicate the important core functions in telemedicine initiatives as well as the diversity of their circumstances. Insights from such historical meta-perspectives can, for example, help to strengthen the sustainability of the increased use of telemedicine during the COVID-19 pandemic and scale up current telemedicine projects.