bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity in treatment effects across diverse populations
Authors: Nugent Bridget M. , Madabushi Rajanikanth , Buch Barbara , Peiris Vasum , Crentsil Victor , Miller Virginia M. , Bull Jonca , R. Jenkins Marjorie 
Published: August 2021

AbstractDifferences in patient characteristics, including age, sex, and race influence the safety and effectiveness of drugs, biologic products, and medical devices. Here we provide a summary of the topics discussed during the opening panel at the 2018 Johns Hopkins Center for Excellence in Regulatory Science and Innovation symposium on Assessing and Communicating Heterogeneity of Treatment Effects for Patient Subpopulations: Challenges and Opportunities. The goal of this session was to provide a brief overview of FDA‐regulated therapeutics, including drugs, biologics and medical devices, and some of the major sources of heterogeneity of treatment effects (HTE) related to patient demographics, such as age, sex and race. The panel discussed the US Food and Drug Administration's role in reviewing and regulating drugs, devices, and biologic products and the challenges associated with ensuring that diverse patient populations benefit from these therapeutics. Ultimately, ensuring diverse demographic inclusion in clinical trials, and designing basic and clinical research studies to account for the intended patient population's age, sex, race, and genetic factors among other characteristics, will lead to better, safer therapies for diverse patient populations.
Lessons learned from 20 years of molecular biological tools in petroleum hydrocarbon remediation
Authors: Taggart Dora M. , Clark Kate 
Published: August 2021

AbstractStakeholders of petroleum hydrocarbon‐contaminated (PHC) sites aim to meet remediation goals cost‐effectively. But contaminated sites are typically complex, and when inefficient remediation strategies are implemented, time and money are wasted. Various strategies can be implemented for site remediation and almost all at some point involve a biological component. Therefore, during site characterization, seeing the complete picture by obtaining multiple lines of evidence—chemistry (concentrations of contaminants and daughter products), geochemistry (redox status, electron acceptors, electron donors), microbiology (species and their genes for catalyzing biodegradation of reactions, i.e., functional genes), and the contaminant degradation ongoing at baseline (stable isotope methods)—is critically important for selecting the best remediation strategy. Additionally, molecular biological evidence is important for monitoring treatment progress and informing decisions to retreat, change treatments, or transition to monitored natural attenuation.
Comparison of Cornell sprinkle infiltrometer and double‐ring infiltrometer methods for measuring steady infiltration rate
Authors: Lewis John , Amoozegar Aziz , McLaughlin Richard A. , Heitman Joshua L. 
Published: August 2021

AbstractInfiltration rate measurements are used to assess soil health and develop land management practices to address runoff from precipitation and irrigation. Differences in observed infiltration rates determined by available methods can be attributed to both the technique and soil property differences. The primary objective of this study was to compare two methods for measuring steady infiltration rate: the Cornell sprinkle infiltrometer (single‐ring) method (CSI), and the double‐ring infiltrometer method (DRI). Measurements were made at four sites using four replications of 13 sets of conditions (52 total paired measurements). The relationship between CSI and DRI measurements was significant (p < .001) and strong (R2 = .71). For 8 of 13 conditions, there was no difference between CSI and DRI steady infiltration rates. Variability in measurements was high (CVs ranged from 0.04 to 1.18) but similar for both methods. Both CSI and DRI results were strongly related to saturated hydraulic conductivity of the surface soil layer determined using a laboratory constant head method on intact soil cores. Overall, results suggest that estimates of steady infiltration rate determined by the CSI and standard DRI methods are comparable.
Detecting Single Molecule Deoxyribonucleic Acid in a Cell Using a Three‐Dimensionally Integrated Nanopore
Authors: Tsutsui Makusu , Yokota Kazumichi , Arima Akihide , Washio Takashi , Baba Yoshinobu , Kawai Tomoji 
Published: August 2021

AbstractAmplification‐free genome analysis can revolutionize biology and medicine by uncovering genetic variations among individuals. Here, the authors report on a 3D‐integrated nanopore for electrolysis to in situ detection of single‐molecule DNA in a cell by ionic current measurements. It consists of a SiO2 multipore sheet and a SiNx nanopore membrane stacked vertically on a Si wafer. Single cell lysis is demonstrated by 106 V m−1‐level electrostatic field focused at the multinanopore. The intracellular molecules are then directly detected as they move through a sensing zone, wherein the authors find telegraphic current signatures reflecting folding degrees of freedom of the millimeter‐long polynucleotides threaded through the SiNx nanopore. The present device concept may enable on‐chip single‐molecule sequencing to multi‐omics analyses at a single‐cell level.
Exploiting dijet resonance searches for flavor physics
Authors: Bordone Marzia , Greljo Admir , Marzocca David 
Published: August 2021

Abstract
In this work, we reinterpret ATLAS and CMS dijet resonance searches to set robust constraints on all hypothetical tree-level scalar and vector mediators with masses up to 5 TeV, assuming a diquark or a quark-antiquark coupling with an arbitrary flavor composition. To illustrate the application of these general results, we quantify the permissible size of new physics in $$ {\overline{B}}_q\to {D}_q^{\left(\ast \right)+}\left\{\pi, K\right\} $$

B
¯

q

→

D
q

∗

+

π
K

consistent with the absence of signal in dijet resonance searches. Along the way, we perform a full SMEFT analysis of the aforementioned non-leptonic B meson decays at leading-order in αs. Our findings uncover a pressing tension between the new physics explanations of recently reported anomalies in these decays and the dijet resonant searches. The high-pT constraints are crucial to drain the parameter space consistent with the low-pT flavor physics data.
Chern-Simons invariants from ensemble averages
Authors: Ashwinkumar Meer , Dodelson Matthew , Kidambi Abhiram , Leedom Jacob M. , Yamazaki Masahito 
Published: August 2021

AbstractWe discuss ensemble averages of two-dimensional conformal field theories associated with an arbitrary indefinite lattice with integral quadratic formQ. We provide evidence that the holographic dual after the ensemble average is the three-dimensional Abelian Chern-Simons theory with kinetic term determined byQ. The resulting partition function can be written as a modular form, expressed as a sum over the partition functions of Chern-Simons theories on lens spaces. For odd lattices, the dual bulk theory is a spin Chern-Simons theory, and we identify several novel phenomena in this case. We also discuss the holographic duality prior to averaging in terms of Maxwell-Chern-Simons theories.
Holographic quantum tasks with input and output regions
Authors: May Alex 
Published: August 2021

Abstract
Quantum tasks are quantum computations with inputs and outputs occurring at specified spacetime locations. Considering such tasks in the context of AdS/CFT has led to novel constraints relating bulk geometry and boundary entanglement. In this article we consider tasks where inputs and outputs are encoded into extended spacetime regions, rather than the points previously considered. We show that this leads to stronger constraints than have been derived in the point based setting. In particular we improve the connected wedge theorem, appearing earlier in arXiv:1912.05649, by finding a larger bulk region whose existence implies large boundary correlation. As well, we show how considering extended input and output regions leads to non-trivial statements in Poincaré-AdS2+1, a setting where the point-based connected wedge theorem is always trivial.
Sleep disorders in people with type 2 diabetes and associated health outcomes: a review of the literature
Authors: Schipper Samantha B. J. , Van Veen Maaike M. , Elders Petra J. M. , van Straten Annemieke , Van Der Werf Ysbrand D. , Knutson Kristen L. , Rutters Femke 
Published: August 2021

AbstractSleep disorders are linked to development of type 2 diabetes and increase the risk of developing diabetes complications. Treating sleep disorders might therefore play an important role in the prevention of diabetes progression. However, the detection and treatment of sleep disorders are not part of standardised care for people with type 2 diabetes. To highlight the importance of sleep disorders in people with type 2 diabetes, we provide a review of the literature on the prevalence of sleep disorders in type 2 diabetes and the association between sleep disorders and health outcomes, such as glycaemic control, microvascular and macrovascular complications, depression, mortality and quality of life. Additionally, we examine the extent to which treating sleep disorders in people with type 2 diabetes improves these health outcomes. We performed a literature search in PubMed from inception until January 2021, using search terms for sleep disorders, type 2 diabetes, prevalence, treatment and health outcomes. Both observational and experimental studies were included in the review. We found that insomnia (39% [95% CI 34, 44]), obstructive sleep apnoea (55–86%) and restless legs syndrome (8–45%) were more prevalent in people with type 2 diabetes, compared with the general population. No studies reported prevalence rates for circadian rhythm sleep–wake disorders, central disorders of hypersomnolence or parasomnias. Additionally, several cross-sectional and prospective studies showed that sleep disorders negatively affect health outcomes in at least one diabetes domain, especially glycaemic control. For example, insomnia is associated with increased HbA1c levels (2.51 mmol/mol [95% CI 1.1, 4.4]; 0.23% [95% CI 0.1, 0.4]). Finally, randomised controlled trials that investigate the effect of treating sleep disorders in people with type 2 diabetes are scarce, based on a small number of participants and sometimes inconclusive. Conventional therapies such as weight loss, sleep education and cognitive behavioural therapy seem to be effective in improving sleep and health outcomes in people with type 2 diabetes. We conclude that sleep disorders are highly prevalent in people with type 2 diabetes, negatively affecting health outcomes. Since treatment of the sleep disorder could prevent diabetes progression, efforts should be made to diagnose and treat sleep disorders in type 2 diabetes in order to ultimately improve health and therefore quality of life.
Graphical abstract
Complication after Aquafilling® gel-mediated augmentation mammoplasty—galactocele formation in a lactating woman: a case report and review of literature
Authors: Loesch Julie Marie , Eniste Yasemin-Sibel , Dedes Konstantin J. , Frauchiger-Heuer Heike 
Published: August 2021

AbstractAugmentation mammoplasty using hydrogel fillers such as polyacrylamide gel (PAAG) or Aquafilling® has been performed commonly in some countries as an alternative to breast augmentation with saline or silicone implants. However, the safety of this procedure remains controversial, and many complications associated with the use of large-volume hydrogel injection have been reported in recent years. We present the case of a 33-year-old woman with a history of bilateral Aquafilling® injection augmentation mammoplasty who presented with an enlarged left breast while breastfeeding. Based on the clinical presentation and ultrasound findings, the patient underwent surgical incision as abscess formation caused by infection of the filler material could not be ruled out with certainty. Surgery revealed a galactocele with drainage of large amounts of milky fluid. Remaining filler material was removed as thoroughly as possible, and vacuum assisted wound dressing was performed. Galactocele formation in lactating women is a known complication after injection of hydrogel. Hence, it is important to be familiar with this uncommon but possibly severe complication in order to make an accurate diagnosis and initiate adequate treatment. To that end, it is recommended that patients who underwent Aquafilling® injection for breast augmentation should avoid lactation and that women intending to breastfeed should not undergo augmentation mammoplasty with injection of Aquafilling®.Level of Evidence: Level V, risk / prognostic study
Characterising cognitive heterogeneity in individuals at clinical high-risk for psychosis: a cluster analysis with clinical and functional outcome prediction
Authors: Haining Kate , Gajwani Ruchika , Gross Joachim , Gumley Andrew I. , Ince Robin A. A. , Lawrie Stephen M. , Schultze-Lutter Frauke , Schwannauer Matthias , Uhlhaas Peter J. 
Published: August 2021

AbstractSchizophrenia is characterised by cognitive impairments that are already present during early stages, including in the clinical high-risk for psychosis (CHR-P) state and first-episode psychosis (FEP). Moreover, data suggest the presence of distinct cognitive subtypes during early-stage psychosis, with evidence for spared vs. impaired cognitive profiles that may be differentially associated with symptomatic and functional outcomes. Using cluster analysis, we sought to determine whether cognitive subgroups were associated with clinical and functional outcomes in CHR-P individuals. Data were available for 146 CHR-P participants of whom 122 completed a 6- and/or 12-month follow-up; 15 FEP participants; 47 participants not fulfilling CHR-P criteria (CHR-Ns); and 53 healthy controls (HCs). We performed hierarchical cluster analysis on principal components derived from neurocognitive and social cognitive measures. Within the CHR-P group, clusters were compared on clinical and functional variables and examined for associations with global functioning, persistent attenuated psychotic symptoms and transition to psychosis. Two discrete cognitive subgroups emerged across all participants: 45.9% of CHR-P individuals were cognitively impaired compared to 93.3% of FEP, 29.8% of CHR-N and 30.2% of HC participants. Cognitively impaired CHR-P participants also had significantly poorer functioning at baseline and follow-up than their cognitively spared counterparts. Specifically, cluster membership predicted functional but not clinical outcome. Our findings support the existence of distinct cognitive subgroups in CHR-P individuals that are associated with functional outcomes, with implications for early intervention and the understanding of underlying developmental processes.
Interpretation of vaccine associated neurological adverse events: a methodological and historical review
Authors: Cauchi Marija , Ball Harriet , Ben-Shlomo Yoav , Robertson Neil 
Published: August 2021

AbstractAs a result of significant recent scientific investment, the range of vaccines available for COVID-19 prevention continues to expand and uptake is increasing globally. Although initial trial safety data have been generally reassuring, a number of adverse events, including vaccine induced thrombosis and thrombocytopenia (VITT), have come to light which have the potential to undermine the success of the vaccination program. However, it can be difficult to interpret available data and put these into context and to communicate this effectively. In this review, we discuss contemporary methodologies employed to investigate possible associations between vaccination and adverse neurological outcomes and why determining causality can be challenging. We demonstrate these issues by discussing relevant historical exemplars and explore the relevance for the current pandemic and vaccination program. We also discuss challenges in understanding and communicating such risks to clinicians and the general population within the context of the ‘infodemic’ facilitated by the Internet and other media.
Severe hospital-acquired hyponatremia in acutely ill children receiving moderately hypotonic fluids
Authors: Lehtiranta Saara , Honkila Minna , Kallio Merja , Halt Kimmo , Paalanne Niko , Pokka Tytti , Tapiainen Terhi 
Published: August 2021

Abstract
Background
Hypotonic fluids have been associated with hospital-acquired hyponatremia. The incidence of life-threatening severe hyponatremia associated with hypotonic fluids has not been evaluated.

Methods
This was a population-based cohort study of 46,518 acutely ill children 15 years of age or under who visited the pediatric emergency department (ED) at Oulu University Hospital, Finland, between 2007 and 2017. We retrieved all electrolyte measurements from the comprehensive electronic laboratory system and reviewed medical records for all patients with severe hyponatremia.

Results
The overall occurrence of severe hyponatremia (serum sodium < 125 mmol/L) was found in 27 out of 46,518 acutely ill children (0.06%, 95% confidence interval 0.04–0.08%). After admission, severe hyponatremia developed in seven of 6,984 children receiving moderately hypotonic fluid therapy (0.1%, 95% confidence interval 0.04–0.2%), usually within 8 h of admission. All children who developed severe hyponatremia during hospitalization were severely ill.

Conclusion
In this register-based cohort study of children presenting to the ED, severe hyponatremia developed in one of 998 acutely ill children receiving moderately hypotonic fluid therapy.

Graphical abstract
A higher resolution version of the Graphical abstract is available as Supplementary information
Surgical management of anterior clinoidal meningiomas: consensus statement on behalf of the EANS skull base section
Authors: Starnoni D. , Tuleasca C. , Giammattei L. , Cossu G. , Bruneau M. , Berhouma M. , Cornelius J. F. , Cavallo L. , Froelich S. , Jouanneau E. , Meling T. R. , Paraskevopoulos D. , Schroeder H. , Tatagiba M. , Zazpe I. , Sufianov A. , Sughrue M. E. , Chacko Ari G. , Benes V. , González-Lopez P. , Roche Pierre-Hugues , Levivier Marc , Messerer Mahmoud , Daniel Roy T. 
Published: August 2021

Abstract
Background
The optimal management of clinoidal meningiomas (CMs) continues to be debated.

Methods
We constituted a task force comprising the members of the EANS skull base committee along with international experts to derive recommendations for the management of these tumors. The data from the literature along with contemporary practice patterns were discussed within the task force to generate consensual recommendations.

Results and conclusion
This article represents the consensus opinion of the task force regarding pre-operative evaluations, patient’s counselling, surgical classification, and optimal surgical strategy. Although this analysis yielded only Class B evidence and expert opinions, it should guide practitioners in the management of patients with clinoidal meningiomas and might form the basis for future clinical trials.
Goal-driven active learning
Authors: Bougie Nicolas , Ichise Ryutaro 
Published: August 2021

AbstractDeep reinforcement learning methods have achieved significant successes in complex decision-making problems. In fact, they traditionally rely on well-designed extrinsic rewards, which limits their applicability to many real-world tasks where rewards are naturally sparse. While cloning behaviors provided by an expert is a promising approach to the exploration problem, learning from a fixed set of demonstrations may be impracticable due to lack of state coverage or distribution mismatch—when the learner’s goal deviates from the demonstrated behaviors. Besides, we are interested in learning how to reach a wide range of goals from the same set of demonstrations. In this work we propose a novel goal-conditioned method that leverages very small sets of goal-driven demonstrations to massively accelerate the learning process. Crucially, we introduce the concept of active goal-driven demonstrations to query the demonstrator only in hard-to-learn and uncertain regions of the state space. We further present a strategy for prioritizing sampling of goals where the disagreement between the expert and the policy is maximized. We evaluate our method on a variety of benchmark environments from the Mujoco domain. Experimental results show that our method outperforms prior imitation learning approaches in most of the tasks in terms of exploration efficiency and average scores.
Unilateral Blinking: Insights from Stereo-EEG and Tractography
Authors: Kaufmann Elisabeth , Bartkiewicz Joanna , Fearns Nicholas , Ernst Katharina , Vollmar Christian , Noachtar Soheyl 
Published: August 2021

AbstractTo study the neuroanatomical correlate of involuntary unilateral blinking in humans, using the example of patients with focal epilepsy. Patients with drug resistant focal epilepsy undergoing presurgical evaluation with stereotactically implanted EEG-electrodes (sEEG) were recruited from the local epilepsy monitoring unit. Only patients showing ictal unilateral blinking or unilateral blinking elicited by direct electrical stimulation were included (n = 16). MRI and CT data were used for visualization of the electrode positions. In two patients, probabilistic tractography with seeding from the respective electrodes was additionally performed. Three main findings were made: (1) involuntary unilateral blinking was associated with activation of the anterior temporal region, (2) tractography showed widespread projections to the ipsilateral frontal, pericentral, occipital, limbic and cerebellar regions and (3) blinking was observed predominantly in female patients with temporal lobe epilepsies. Unilateral blinking was found to be associated with an ipsilateral activation of the anterior temporal region. We suggest that the identified network is not part of the primary blinking control but might have modulating influence on ipsilateral blinking by integrating contextual information.
Plasma membrane glycosphingolipid signaling: a turning point
Authors: Chiricozzi Elena 
Published: August 2021

AbstractPlasma membrane interaction is highly recognized as an essential step to start the intracellular events in response to extracellular stimuli. The ways in which these interactions take place are less clear and detailed. Over the last decade my research has focused on developing the understanding of the glycosphingolipids-protein interaction that occurs at cell surface. By using chemical synthesis and biochemical approaches we have characterized some fundamental interactions that are key events both in the immune response and in the maintenance of neuronal homeostasis. In particular, for the first time it has been demonstrated that a glycolipid, present on the outer side of the membrane, the long-chain lactosylceramide, is able to directly modulate a cytosolic protein. But the real conceptual change was the demonstration that the GM1 oligosaccharide chain is able, alone, to replicate numerous functions of GM1 ganglioside and to directly interact with plasma membrane receptors by activating specific cellular signaling. In this conceptual shift, the development and application of multidisciplinary techniques in the field of biochemistry, from chemical synthesis to bioinformatic analysis, as well as discussions with several national and international colleagues have played a key role.