bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Bone Turnover Associates With Lower Insulin Sensitivity in Newly Diagnosed Drug-Naïve Persons With Type 2 Diabetes
Authors: Nasser Mohamad I , Stidsen Jacob V , Højlund Kurt , Nielsen Jens Steen , Eastell Richard , Frost Morten 
Published: January 2023

Abstract

Context
Bone turnover markers (BTMs) are lower in type 2 diabetes mellitus (T2D). The relationships between bone turnover, β-cell function, and insulin sensitivity in T2D are uncertain.

Objective
To investigate if fasting levels of BTMs in persons with T2D are associated with β-cell function or insulin sensitivity.

Methods
We defined three T2D phenotypes, the insulinopenic (low β-cell function, high insulin sensitivity), the classical (low β-cell function, low insulin sensitivity), and the hyperinsulinemic (high β-cell function, low insulin sensitivity) phenotypes, in the Danish Centre for Strategic Research T2D cohort using the homeostatic model assessment. We selected age- and gender-matched subgroups to represent the three T2D phenotypes, yielding 326 glucose-lowering treatment–naïve persons with T2D. Median values of BTMs between the three T2D phenotypes were compared. Regression models were applied to assess the association between BTMs, β-cell function, and insulin sensitivity adjusted for potential confounders.

Results
Median serum levels of procollagen type I N-terminal propeptide, C-terminal telopeptide of type I collagen, and osteocalcin were higher in the insulinopenic phenotype (52.3 μg/L, IQR 41.6, 63.3; 259.4 ng/L, IQR 163.4, 347.7; and 18.0 μg/L, IQR 14.4, 25.2, respectively) compared with the classical (41.4, IQR 31.0, 51.4; 150.4 IQR 103.5, 265.1; 13.1, IQR 10.0, 17.6, respectively) and the hyperinsulinemic (43.7, IQR 32.3, 57.3; 163.3, IQR 98.9, 273.1; 15.7 IQR 10.2, 20.8, respectively) phenotypes (all P &lt; .01). These differences persisted after adjustment for age, sex, waist to hip ratio, or fasting plasma glucose (P &lt; .01).

Conclusion
BTMs are lower in newly diagnosed persons with T2D characterized by low insulin sensitivity.
Technical Nuances and Outcomes of Telescoping Pipeline Flow Diverters: A Multicenter Study
Authors: Baker Cordell M. , Hunsaker Joshua C. , Folzenlogen Zach A. , Pride Glenn L. , Case David E. , Welch Babu G. , White Jonathan A. , Roark Christopher D. , White Andrew C. , Seinfeld Joshua , Muse John , Grandhi Ramesh , Taussky Philipp 
Published: January 2023

BACKGROUND:
“Telescoping” multiple overlapping Pipeline Embolization Devices (PEDs; Medtronic) has increased their utility by allowing for more impermeable coverage and providing the ability to off-set landing zone sites and extend treatment constructs.

OBJECTIVE:
To consider the technical nuances and challenges of telescoping PEDs for the treatment of intracranial aneurysms.

METHODS:
Databases from 3 U.S. academic neurovascular centers were retrospectively queried to identify patients with intracranial aneurysms treated with multiple PED constructs. Data on patient and aneurysm characteristics, as well as outcomes including Raymond-Roy occlusion classification, modified Rankin Scale score, and complications, were gathered.

RESULTS:
Forty-six patients had 48 intracranial aneurysms treated, including 16 (33%) in whom placement of telescoping PEDs was planned. Fourteen (30%) patients presented with a ruptured aneurysm. Twenty-one aneurysms (44%) were treated with proximal extension, 13 (27%) with distal extension, and 14 (29%) with PED placement inside one another. Thirty (70%) patients had complete aneurysm occlusion at follow-up. Two (4%) patients had to be retreated. Three patients with unruptured and 1 with ruptured aneurysm had a permanent intraprocedural complication. We present descriptive cases illustrating PEDs that were placed inside one another, proximally, distally, and to improve wall apposition because of vessel tortuosity.

CONCLUSION:
Our data indicate a higher than expected complication rate that is likely because of the technical complexity of these cases. The case illustrations presented demonstrate the indications and challenging aspects of telescoping PEDs.
Invertebrates as models of learning and memory: investigating neural and molecular mechanisms
Authors: Rivi Veronica , Benatti Cristina , Rigillo Giovanna , Blom Joan M. C. 
Published: January 2023

ABSTRACT
In this Commentary, we shed light on the use of invertebrates as model organisms for understanding the causal and conserved mechanisms of learning and memory. We provide a condensed chronicle of the contribution offered by mollusks to the studies on how and where the nervous system encodes and stores memory and describe the rich cognitive capabilities of some insect species, including attention and concept learning. We also discuss the use of planarians for investigating the dynamics of memory during brain regeneration and highlight the role of stressful stimuli in forming memories. Furthermore, we focus on the increasing evidence that invertebrates display some forms of emotions, which provides new opportunities for unveiling the neural and molecular mechanisms underlying the complex interaction between stress, emotions and cognition. In doing so, we highlight experimental challenges and suggest future directions that we expect the field to take in the coming years, particularly regarding what we, as humans, need to know for preventing and/or delaying memory loss.
This article has an associated ECR Spotlight interview with Veronica Rivi.
Delayed Sentinel Lymph Node Dissection in Patients with a Preoperative Diagnosis of Ductal Cancer In Situ by Preoperative Injection with Superparamagnetic Iron Oxide (SPIO) Nanoparticles: The SentiNot Study
Authors: Karakatsanis Andreas , Eriksson Staffan , Pistiolis Lida , Olofsson Bagge Roger , Nagy Gyula , Man Vivian , Kwong Ava , Wärnberg Fredrik ,   the SentiNot Trialists Group, Mohammed Imad , Hersi Abdi Fatah , Jazrawi Allan , Olofsson Helena , Stålberg Peter 
Published: January 2023

Abstract
Background
Difficulty in preoperatively assessing the risk for occult invasion or surgery that precludes future accurate axillary mapping in patients with ductal cancer in situ (DCIS) account for overutilization of SLND.

Methods
Prospective, multicenter, cohort study, including women with any DCIS planned for mastectomy or DCIS grade 2 and > 20 mm, any DCIS grade 3, any mass-forming DCIS and any planned surgery. Patients received an interstitial SPIO injection during breast surgery, but no upfront SLND was performed. If invasion was identified on final pathology, delayed SLND (d-SLND) was performed separately with the coadministration of isotope ± blue dye (BD). Study outcomes were proportion of upfront SLNDs that were avoided, detection rates during d-SLND, and impact on healthcare costs.

Results
In total, 78.7% of study participants (N = 254, mean age 60 years, mean DCIS size 37.8 mm) avoided upfront SLND. On d-SLND (median 28 days, range 9–46), SPIO outperformed Tc99 with (98.2% vs. 63.6%, p < 0.001) or without BD (92.7% vs. 50.9%, p < 0.001) and had higher nodal detection rate (86.9% vs. 32.3%, p < 0.001) and with BD (93.9% vs. 41.4%, p < 0.001). Only 27.9% of all SLNs retrieved were concordant for Tc99 and SPIO. Type of breast procedure (WLE vs. oncoplastic BCT vs. mastectomy) affected these outcomes and accounted for the low performance of Tc99 (p < 0.001). d-SLND resulted in a 28.1% total cost containment for women with pure DCIS on final pathology (4190 vs. 5828 USD, p < 0.001).

Conclusions
Marking the SLN with SPIO may avoid overtreatment and allow for accurate d-SLND in patients with DCIS.
Caffeine Augments the Lactate and Interleukin-6 Response to Moderate-Intensity Exercise
Authors: ABBOTTS KIERAN SHAY STRUEBIN , EWELL TAYLOR RUSSELL , BOMAR MATTHEW CHARLES , BUTTERKLEE HANNAH MICHELLE , BELL CHRISTOPHER 
Published: January 2023

ABSTRACT

Introduction
The release of interleukin (IL)-6 from contracting skeletal muscle is thought to contribute to some of the health benefits bestowed by exercise. This IL-6 response seems proportional to exercise volume and to lactate production. Unfortunately, high volumes of exercise are not feasible for all people. Caffeine augments the magnitude of increase in circulating IL-6 in response to high-intensity and long-duration exercise. Caffeine also increases circulating concentrations of lactate during exercise. We hypothesized that caffeine, ingested before short-duration, moderate-intensity exercise, would lead to greater circulating concentrations of lactate and IL-6 in a study population comprising both male and female individuals.

Methods
Twenty healthy adults (10 men and 10 women age 25 ± 7 yr (mean ± SD)) completed 30 min of moderate-intensity cycle ergometer exercise, at an intensity corresponding to 60% peak oxygen uptake, after ingesting either caffeine (6 mg·kg−1) or placebo. Arterialized-venous blood was collected throughout each of the exercise sessions.

Results
Compared with placebo, caffeine increased circulating concentrations of lactate at the end of exercise (5.12 ± 3.67 vs 6.45 ± 4.40 mmol·L−1, P < 0.001) and after 30 min of inactive recovery (1.83 ± 1.59 vs 2.32 ± 2.09 mmol·L−1, P = 0.006). Circulating IL-6 concentrations were greatest after 30 min of inactive recovery (P < 0.001) and higher with caffeine (2.88 ± 2.05 vs 4.18 ± 2.97, pg·mL−1, P < 0.001). Secondary analysis indicated sex differences; caffeine increased the IL-6 response to exercise in men (P = 0.035) but not in women (P = 0.358).

Conclusions
In response to moderate-intensity exercise, caffeine evoked greater circulating lactate concentrations in men and women but only increased the IL-6 response to exercise in men. These novel findings suggest that for men unwilling or unable to perform high-intensity and/or long-duration exercise, caffeine may augment the health benefits of relatively short, moderate-intensity exercise.
Active Heat Acclimation Does Not Alter Muscle–Tendon Unit Properties
Authors: MORNAS ADÈLE , BROCHERIE FRANCK , GUILHEM GAËL , GUILLOTEL ARTHUR , LE GARREC SÉBASTIEN , GOUWY RITSE , GENNISSON JEAN-LUC , BEUVE STEVE , RACINAIS SÉBASTIEN 
Published: January 2023

ABSTRACT

Purpose
Heat acclimation (HA) is recommended before competing in hot and humid conditions. HA has also been recently suggested to increase muscle strength, but its effects on human’s muscle and tendon mechanical properties are not yet fully understood. This study investigated the effect of active HA on gastrocnemius medialis (GM) muscle–tendon properties.

Methods
Thirty recreationally active participants performed 13 low-intensity cycling sessions, distributed over a 17-d period in hot (HA = ~38°C, ~58% relative humidity; n = 15) or in temperate environment (CON = ~23°C, ~35% relative humidity; n = 15). Mechanical data and high-frame rate ultrasound images were collected during electrically evoked and voluntary contractions pre- and postintervention. Shear modulus was measured at rest in GM, and vertical jump performance was assessed.

Results
Core temperature decreased from the first to the last session in HA (−0.4°C ± 0.3°C; P = 0.015), while sweat rate increased (+0.4 ± 0.3 L·h−1; P = 0.010), suggesting effective HA, whereas no changes were observed in CON (both P ≥ 0.877). Heart rate was higher in HA versus CON and decreased throughout intervention in groups (both P ≤ 0.008), without an interaction effect (P = 0.733). Muscle–tendon unit properties (i.e., maximal and explosive isometric torque production, contractile properties, voluntary activation, joint and fascicular force–velocity relationship, passive muscle, and active tendon stiffness) and vertical jump performance did not show training (P ≥ 0.067) or group–training interaction (P ≥ 0.232) effects.

Conclusions
Effective active HA does not alter muscle–tendon properties. Preparing hot and humid conditions with active HA can be envisaged in all sporting disciplines without the risk of impairing muscle performance.
Clonal Kinetics and Single-Cell Transcriptional Profiles of T Cells Mobilized to Blood by Acute Exercise
Authors: ZÚÑIGA TIFFANY M. , BAKER FORREST L. , SMITH KYLE A. , BATATINHA HELENA , LAU BRANDEN , BURGESS SHANE C. , GUSTAFSON MICHAEL P. , KATSANIS EMMANUEL , SIMPSON RICHARD J. 
Published: January 2023

ABSTRACT

Purpose
Acute exercise redistributes large numbers of memory T cells, which may contribute to enhanced immune surveillance in regular exercisers. It is not known, however, if acute exercise promotes a broad or oligoclonal T-cell receptor (TCR) repertoire or evokes transcriptomic changes in “exercise-responsive” T-cell clones.

Methods
Healthy volunteers completed a graded bout of cycling exercise up to 80% V̇O2max. DNA was extracted from peripheral blood mononuclear cells collected at rest, during exercise (EX), and 1 h after (+1H) exercise, and processed for deep TCR-β chain sequencing and tandem single-cell RNA sequencing.

Results
The number of unique clones and unique rearrangements was decreased at EX compared with rest (P < 0.01) and +1H (P < 0.01). Productive clonality was increased compared with rest (P < 0.05) and +1H (P < 0.05), whereas Shannon’s Index was decreased compared with rest (P < 0.05) and +1H (P < 0.05). The top 10 rearrangements in the repertoire were increased at EX compared with rest (P < 0.05) and +1H (P < 0.05). Cross-referencing TCR-β sequences with a public database (VDJdb) revealed that exercise increased the number of clones specific for the most prevalent motifs, including Epstein–Barr virus, cytomegalovirus, and influenza A. We identified 633 unique exercise-responsive T-cell clones that were mobilized and/or egressed in response to exercise. Among these clones, there was an upregulation in genes related to cell death, cytotoxicity, and activation (P < 0.05).

Conclusions
Acute exercise promotes an oligoclonal T-cell repertoire by preferentially mobilizing the most dominant clones, several of which are specific to known viral antigens and display differentially expressed genes indicative of cytotoxicity, activation, and apoptosis.
Heatwave 1987: the Piraeus versus Athens case
Authors: Geronikolou Stella , Zimeras Stelios , Tsitomeneas Stephanos , Chrousos George P 
Published: January 2023

Background: Heatwaves represent the main indices of climate change, while mortality is one of the established markers of their human effects. Populations adapt to temperature variations/challenges differently for unknown reasons. Thus, heatwave evaluations should be enriched by historical context and local data, to allow better precision and prediction. Methods: The mortality data for 1987 were collected from the Piraeus municipality registry, whereas data for Athens were obtained from literature retrieved from PUBMED. Ambient characteristics were derived from Geronikolou’s 1991 thesis and the reports of national organizations. From the death events, the odds ratio and relative risk in Athens compared to the Piraeus 1987 event were calculated. Finally, a simple neural network proposed the dominant ambient parameter of the heatwave phenomenon in each place. Results: The 1987 heatwave was more lethal (seven-fold) in Athens than in Piraeus and was found to be dependent on nitric oxide (NO) concentration (with probability 0.999). In the case of Piraeus in 1987, ozone characterized the phenomenon. Conclusions: The odds of dying due to a heatwave are highly dependent on lifestyle, population sensitivity to preventive measures and public health policy, while the phenomenon was mainly moderated by ozone in Piraeus in 1987, and NO in Athens irrespective of year.
Subcellular protein localisation of Trypanosoma brucei bloodstream form-upregulated proteins maps stage-specific adaptations
Authors: Halliday Clare , Dean Samuel , Sunter Jack Daniel , Wheeler Richard J. 
Published: January 2023

Background: Genome-wide subcellular protein localisation in Trypanosoma brucei, through our TrypTag project, has comprehensively dissected the molecular organisation of this important pathogen. Powerful as this resource is, T. brucei has multiple developmental forms and we previously only analysed the procyclic form. This is an insect life cycle stage, leaving the mammalian bloodstream form unanalysed. The expectation is that between life stages protein localisation would not change dramatically (completely unchanged or shifting to analogous stage-specific structures). However, this has not been specifically tested. Similarly, which organelles tend to contain proteins with stage-specific expression can be predicted from known stage specific adaptations but has not been comprehensively tested. Methods: We used endogenous tagging with mNG to determine the sub-cellular localisation of the majority of proteins encoded by transcripts significantly upregulated in the bloodstream form, and performed comparison to the existing localisation data in procyclic forms. Results: We have confirmed the localisation of known and identified the localisation of novel stage-specific proteins. This gave a map of which organelles tend to contain stage specific proteins: the mitochondrion for the procyclic form, and the endoplasmic reticulum, endocytic system and cell surface in the bloodstream form. Conclusions: This represents the first genome-wide map of life cycle stage-specific adaptation of organelle molecular machinery in T. brucei.
EXPORT OF AGRO-INDUSTRIAL PRODUCTS OF RUSSIA: NEW OPPORTUNITIES AND DEVELOPMENT PROBLEMS
Authors: Butakova Marina M. , Sokolova Olga N. , Churina Larisa I. 
Published: January 2023

The paper considers the export problem of the agro-industrial products of Russia. The research relevance lies in the competition conditions in the world food markets. The paper aims to study the impact of the development of exports of agricultural products on the stability of the Russian economy.
Considering the strengthening of the position of agricultural products export in the structure of Russian exports, the paper aims to assess the problems and identify new opportunities for the development of agricultural products exports based on an analysis of its dynamics and structure.
The authors applied the methods of economic-statistical analysis to identify patterns in the dynamics and structure of exports of agricultural products. During the research, the dynamics and structure of agricultural exports were analyzed. The authors also calculated the average export price for the enlarged product groups. They concluded that (1) the share of agricultural exports in the structure of Russian exports is growing and (2) that there is a need to increase its efficiency through government support measures. New opportunities for the export of agricultural products in the world market arise with (1) an increase of the competitiveness of products, (2) the development of new sales markets, (3) a stable position of exporters, (4) the efficient production of agricultural products by national producers.
Currently, it is possible only if state support for export activities is combined with the initiatives of the agriculture entrepreneurs. The paper will be useful for regional and federal governments, the scientific community, and anyone interested in Russian export issues.
ON THE PROBLEM OF THE DEVELOPMENT OF ‘SUSTAINABLE’ AGRICULTURE IN MODERN ECONOMIC REALITIES
Authors: Amirova Elmira F. , Gavrilyeva Nadezhda K. , Romanishina Tatyana S. , Asfandiarova Rima A. 
Published: January 2023

Sustainability of agriculture is one of the main directions of development of the industry, which today has a high relevance due to the fact that the industry itself, on the one hand, uses land as the main resource, on the other hand, there is a significant amount of waste in the production of agricultural products, which worsen the environment. Accordingly, the relevance of the topic under consideration is determined by the need to solve the problem of finding a balance between the need to intensify the level of agricultural production and the preservation of environmental well-being. The purpose of the work is to consider the problematic aspects of the development of “sustainable” agriculture in modern economic realities and identify ways to solve certain problems. In the course of the research, the works of various specialists in the field under consideration were analyzed, on the basis of which a review of the author’s positions regarding the problem under consideration was conducted.
According to the results of the study, the following conclusion was made: the direction analysis of the sustainable agriculture development showed that in modern conditions it is necessary to focus on a set of indicators that will assess the level of decline in environmental well-being in a particular region and determine the directions of reducing the harmful impact of agriculture on the environment.
However, taking into account the complex nature of agricultural systems and multidimensional sustainability issues, a single change in agriculture (for example, the introduction of a new technology or a new policy) can lead to multiple cascading impacts on three aspects of sustainability, and therefore some of the performance indicators may improve and others may worsen. Thus, understanding the compromises and synergies between indicators is crucial for policy makers when developing strategies aimed at ensuring sustainability.
Data-Driven COVID-19 Vaccine Development for Janssen
Authors: Bertsimas Dimitris , Li Michael Lingzhi , Liu Xinggang , Xu Jennings , Khan Najat 
Published: January 2023

The COVID-19 pandemic has spurred extensive vaccine research worldwide. One crucial part of vaccine development is the phase III clinical trial that assesses the vaccine for safety and efficacy in the prevention of COVID-19. In this work, we enumerate the first successful implementation of using machine learning models to accelerate phase III vaccine trials, working with the single-dose Johnson & Johnson vaccine to predictively select trial sites with naturally high incidence rates (“hotspots”). We develop DELPHI, a novel, accurate, policy-driven machine learning model that serves as the basis of our predictions. During the second half of 2020, the DELPHI-driven site selection identified hotspots with more than 90% accuracy, shortened trial duration by six to eight weeks (approximately 33%), and reduced enrollment by 15,000 (approximately 25%). In turn, this accelerated time to market enabled Janssen’s vaccine to receive its emergency use authorization and realize its public health impact earlier than expected. Several geographies identified by DELPHI have since been the first areas to report variants of concern (e.g., Omicron in South Africa), and thus DELPHI’s choice of these areas also produced early data on how the vaccine responds to new threats. Johnson & Johnson has also implemented a similar approach across its business including supporting trial site selection for other vaccine programs, modeling surgical procedure demand for its Medical Device unit, and providing guidance on return-to-work programs for its 130,000 employees. Continued application of this methodology can help shorten clinical development and change the economics of drug development by reducing the level of risk and cost associated with investing in novel therapies. This will allow Johnson & Johnson and others to enable more effective delivery of medicines to patients. Funding: This work was funded by Janssen Research & Development, LLC.