bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovation in sport medicine and science: a global social network analysis of stakeholder collaboration in rugby union
Authors: Erskine Natalie R , Hendricks Sharief , Jones Ben , Salie Faatiema
Published: March 2024

Objectives

To investigate the network of stakeholders involved in rugby union research across the globe.

Methods

Using author affiliations listed on scientific publications, we identified the organisations that contributed to rugby union research from 1977 to 2022 and examine collaboration through coauthorship indicators. We determined the locations and sectors of identified organisations and constructed a collaboration network. Network metrics, including degree centrality and betweenness centrality, are computed to identify influential organisations and measure intersector collaboration.

Results

There is an increase in scientific knowledge creation and collaboration between organisations for rugby union research over time. Among the sectors, the university, professional sports team and sports governing body sectors exhibit the highest intersectoral and intrasectoral density. Predominantly, influential actors are located in England, Australia, France, New Zealand, Ireland and South Africa. Australian Catholic University, Leeds Beckett University, Stellenbosch University, Swansea University, University College London and the University of Cape Town emerge as influential actors between 2016 and 2022.

Conclusions

Our study underscores the ongoing growth of scientific knowledge generation in rugby union, primarily led by organisations in tier 1 rugby-playing nations within the university sector. Intersectoral collaboration with sports governing bodies plays a crucial role, acting as a broker between sectors. However, the overall collaboration landscape between and within sectors is low. These results highlight an opportunity for improved collaboration opportunities, as the organisations driving knowledge creation have been identified.
Youth handball concussion prevention strategies: a workshop-based study with experts and end users
Authors: Sturesson Victor , Marforio Peter , Reuter Arlind , Johansson Kajsa , Ageberg Eva
Published: March 2024

Sport-related concussion (SRC) is a serious injury in youth team sports, including handball. While research on the prevention of SRC has made progress over the past 5 years, prevention strategies are lacking in handball. The aim was to explore and develop strategies focusing on information, rules and training that may prevent concussion in youth handball by incorporating knowledge from experts and end users. Using a participatory methodology, experts (physiotherapy, biomechanics: n=3) and end users (players, coaches, referees, coach educators: n=7) contributed their experience and knowledge in a 2-hour online workshop. Participants were given three videos illustrating typical high-risk concussion scenarios from handball games and a youth player’s accompanying fictional written scenario. In group discussions inspired by the brainwriting method, participants were asked to provide ideas for possible SRC prevention strategies related to information, rules and/or training. Data were collected on a digital whiteboard and analysed using reflexive thematic analysis. Three themes were derived: (1) ‘Coaches’ responsibility: raise awareness of the risk of injury and act to promote safe environments’; (2) ‘Players’ responsibility: safe defence and attack’; and (3) ‘Improvement of personal skills’. Experts and end users found information about high-risk situations and SRC symptoms, stricter rules and safe playing strategy training for goalkeepers, attacking and defending players, respectively, may effectively reduce SRC in handball. Information and stricter rules could be delivered through education and dissemination activities, whereas safe playing strategies should be trained at regular handball practice.
Building on muscles: how built environment design impacts modern sports science
Authors: Koohsari Mohammad Javad , Kaczynski Andrew T , Miyachi Motohiko , Oka Koichiro
Published: March 2024

Sports science focuses on enhancing athletes’ performance, requiring a multifaceted approach. It is evolving from a purely muscle-centred approach to an interdisciplinary one. This paper investigates built environment design science, a dimension less explored in relation to enhancing athlete performance in sports science. The discussion is divided into three categories: athlete-centric training built environment design, enhanced fan and community engagement, and improved integrative accessibility. The study also identifies future research directions, including evidence of the relative impact of the built environment, financial aspects, and performance evaluation methods. Collaboration between sports scientists and scholars in urban design, parks, transportation, landscape architecture and environmental psychology is necessary to advance this topic further.
Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars)
Authors: Malekzadeh Fatemeh , Gandomkar Abdullah , Poustchi Hossein , Etemadi Arash , Roshandel Gholamreza , Attar Armin , Abtahi Firoozeh , Sadeghi Boogar Shahrokh , Mohammadkarimi Vahid , Fattahi Mohammad Reza , Mohagheghi Abbas , Malekzadeh Reza , Sepanlou Sadaf G
Published: March 2024

Background

We aimed to investigate the effectiveness of fixed-dose combination therapy (polypill) for primary and secondary prevention of major cardiovascular diseases in a typical rural setting.

Methods

The PolyPars Study is a two-arm pragmatic cluster-randomised trial nested within the PARS cohort study, including all residents aged over 50 years in the entire district in southern Iran. The 91 villages underwent random allocation into two arms: the control arm, encompassing 45 clusters, was subjected to non-pharmacological intervention (educational training on healthy lifestyle), whereas the intervention arm, comprising 46 clusters, received the non-pharmacological interventions in conjunction with a once-daily polypill tablet. This tablet comprised two antihypertensive agents, a statin and aspirin. The primary outcome was the first occurrence of major cardiovascular events defined as a composite of hospitalisation for acute coronary syndrome (non-fatal myocardial infarction and unstable angina), fatal myocardial infarction, non-fatal and fatal stroke, sudden death and heart failure. The Cox regression model, with shared frailty, was used to account for clustering effect.

Results

During December 2015–December 2016, a total of 4415 participants aged 50–75 years were recruited (2200 participants in the intervention arm and 2215 participants in the control arm). The overall median of follow-up duration was 4.6 years (interquartile interval 4.4–4.9). The achieved adherence rate to polypill in intervention arm was 86%. In the control group, 176 (8.0%) of 2215 participants developed primary outcome, compared with 88 (4.0%) of 2200 participants in the polypill group. We found substantial reduction in risk of primary outcome both in relative and absolute scales (HR 0.50, 95% CI 0.38 to 0.65; absolute risk reduction 4.0%, 95% CI 2.5% to 5.3%). No difference in serious adverse events was observed between the two groups.

Conclusions

The fixed-dose combination therapy using polypill can safely halve the risk of major cardiovascular diseases at the population level.

Trial registration number

NCT03459560.
Modified FOLFOX6 plus bevacizumab with and without nivolumab for first-line treatment of metastatic colorectal cancer: phase 2 results from the CheckMate 9X8 randomized clinical trial
Authors: Lenz Heinz-Josef , Parikh Aparna , Spigel David R , Cohn Allen L , Yoshino Takayuki , Kochenderfer Mark , Elez Elena , Shao Spencer H , Deming Dustin , Holdridge Regan , Larson Timothy , Chen Eric , Mahipal Amit , Ucar Antonio , Cullen Dana , Baskin-Bey Edwina , Kang Tong , Hammell Amy B , Yao Jin , Tabernero Josep
Published: March 2024

Background

Standard first-line therapies for metastatic colorectal cancer (mCRC) include fluoropyrimidine-containing regimens with oxaliplatin and/or irinotecan and a biologic agent. Immunotherapy may enhance antitumor activity in combination with standard therapies in patients with mCRC. Here, we present phase 2 results of nivolumab plus standard-of-care therapy (SOC; 5-fluorouracil/leucovorin/oxaliplatin/bevacizumab) versus SOC in the first-line treatment of patients with mCRC (CheckMate 9X8).

Methods

CheckMate 9X8 was a multicenter, open-label, randomized, phase 2/3 trial. Eligible patients were at least 18 years of age with unresectable mCRC and no prior chemotherapy for metastatic disease. Patients were randomized 2:1 to receive nivolumab 240 mg plus SOC or SOC alone every 2 weeks. The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors V.1.1. Secondary endpoints included PFS by investigator assessment; objective response rate (ORR), disease control rate, duration of response, and time to response, all by BICR and investigator assessments; overall survival; and safety. Preplanned exploratory biomarker analyses were also performed.

Results

From February 2018 through April 2019, 310 patients were enrolled, of which 195 patients were randomized to nivolumab plus SOC (n=127) or SOC (n=68). At 21.5-month minimum follow-up, PFS with nivolumab plus SOC versus SOC did not meet the prespecified threshold for statistical significance; median PFS by BICR was 11.9 months in both arms (HR, 0.81 (95% CI, 0.53 to 1.23); p=0.30). Higher PFS rates after 12 months (18 months: 28% vs 9%), higher ORR (60% vs 46%), and durable responses (median 12.9 vs 9.3 months) were observed with nivolumab plus SOC versus SOC. Grade 3–4 treatment-related adverse events were reported in 75% versus 48% of patients; no new safety signals were identified.

Conclusions

The CheckMate 9X8 trial investigating first-line nivolumab plus SOC versus SOC in patients with mCRC did not meet its primary endpoint of PFS by BICR. Nivolumab plus SOC showed numerically higher PFS rates after 12 months, a higher response rate, and more durable responses compared with SOC alone, with acceptable safety. Further investigation to identify subgroups of patients with mCRC that may benefit from nivolumab plus SOC versus SOC in the first-line setting is warranted.

Trial registration number

NCT03414983.
Phase II study of nivolumab in patients with genetic alterations in DNA damage repair and response who progressed after standard treatment for metastatic solid cancers (KM-06)
Authors: Kim Ju Won , Lee Hyo Jin , Lee Ji Yoon , Park Sook Ryun , Kim Yu Jung , Hwang In Gyu , Kyun Bae Woo , Byun Jae Ho , Kim Jung Sun , Kang Eun Joo , Lee Jeeyun , Shin Sang Joon , Chang Won Jin , Kim Eun-Ok , Sa Jason K , Park Kyong Hwa
Published: March 2024

Background

Immune-modulating antibodies targeting programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have demonstrated promising antitumor efficacy in various types of cancers, especially highly mutated ones. Genetic alterations in DNA damage response and repair (DDR) genes can lead to genetic instability, often accompanied by a high tumor mutation burden (TMB). However, few studies have validated the aberration of DDR genes as a predictive biomarker for response to immune-modulating antibodies.

Methods

The KM-06 open-label, multicenter, single-arm, phase II trial evaluated the safety and efficacy of nivolumab in refractory solid cancers with DDR gene mutations assessed by clinically targeted sequencing. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or for 24 months. The primary endpoint was the objective response rate (ORR) as per RECIST V.1.1 criteria.

Results

A total of 48 patients were enrolled in the study (median age 61, 58.3% male). The most common cancer type was colorectal cancer (41.7%), followed by prostate and biliary tract cancer (8.3% each). Eight patients achieved a partial response as their best overall response, resulting in an ORR of 17.8%. The disease control rate was 60.0%. The median progression-free survival was 2.9 months. Treatment-related adverse events of any grade and grade ≥3 occurred in 44 (91.7%) and 4 (8.3%) patients, respectively. Clinically targeted sequencing data inferred both TMB and microsatellite instability (MSI). Using a TMB cut-off of 12 mut/Mb, there were significant differences in overall survival (p=0.00035), progression-free survival (p=0.0061), and the best overall response (p=0.05). In the RNA sequencing analysis, nivolumab responders showed activation of the interleukin signaling pathway. Patients who experienced early progression presented high epithelial-mesenchymal transition signaling pathway activation. The responders exhibited a marked increase in PD-1−/Ki67+CD8 T cells at the early stage of treatment (C3D1) compared with non-responders (p=0.03).

Conclusions

In this phase II trial, nivolumab demonstrated moderate efficacy and manageable toxicity in patients with solid cancer harboring DDR gene mutations. A high TMB (>12 mut/Mb) and MSI score (>2.5) determined through clinically target sequencing presented significant discriminatory power for the nivolumab response.

Trial registration number

NCT04761744.
Biomarkers for response to TIL therapy: a comprehensive review
Authors: Albarrán Fernández Víctor , Ballestín Martínez Pablo , Stoltenborg Granhøj Joachim , Borch Troels Holz , Donia Marco , Marie Svane Inge
Published: March 2024

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated durable clinical responses in patients with metastatic melanoma, substantiated by recent positive results of the first phase III trial on TIL therapy. Being a demanding and logistically complex treatment, extensive preclinical and clinical effort is required to optimize patient selection by identifying predictive biomarkers of response. This review aims to comprehensively summarize the current evidence regarding the potential impact of tumor-related factors (such as mutational burden, neoantigen load, immune infiltration, status of oncogenic driver genes, and epigenetic modifications), patient characteristics (including disease burden and location, baseline cytokines and lactate dehydrogenase serum levels, human leucocyte antigen haplotype, or prior exposure to immune checkpoint inhibitors and other anticancer therapies), phenotypic features of the transferred T cells (mainly the total cell count, CD8:CD4 ratio, ex vivo culture time, expression of exhaustion markers, costimulatory signals, antitumor reactivity, and scope of target tumor-associated antigens), and other treatment-related factors (such as lymphodepleting chemotherapy and postinfusion administration of interleukin-2).
Time to childbirth and assisted reproductive treatment in women with congenital heart disease
Authors: Jonsson Sara , Sundström-Poromaa Inger , Johansson Bengt , Alenius Dahlqvist Jenny , Christersson Christina , Dellborg Mikael , Trzebiatowska-Krzynska Alexandra , Sörensson Peder , Thilén Ulf , Wikström Anna-Karin , Bay Annika
Published: March 2024

Objective

To investigate the time to first childbirth and to compare the prevalence of assisted reproductive treatment (ART) in women with congenital heart disease (CHD) compared with women without CHD.

Methods

All women in the national register for CHD who had a registered first childbirth in the Swedish Pregnancy Register between 2014 and 2019 were identified. These individuals (cases) were matched by birth year and municipality to women without CHD (controls) in a 1:5 ratio. The time from the 18th birthday to the first childbirth and the prevalence of ART was compared between cases and controls.

Results

830 first childbirths in cases were identified and compared with 4137 controls. Cases were slightly older at the time for first childbirth (28.9 vs 28.5 years, p=0.04) and ART was more common (6.1% vs 4.0%, p<0.01) compared with controls. There were no differences in ART when stratifying for the complexity of CHD. For all women, higher age was associated with ART treatment (OR 1.24, 95% CI 1.20 to 1.28).

Conclusions

Women with and without CHD who gave birth to a first child did so at similar ages. ART was more common in women with CHD, but disease severity did not influence the need for ART. Age was an important risk factor for ART also in women with CHD and should be considered in consultations with these patients.
Searching for supermassive charged gravitinos in underground experiments
Authors: Meissner Krzysztof A. , Nicolai Hermann
Published: March 2024

We examine possible experimental signatures that may be exploited to search for stable supermassive particles with electric charges of $${{\mathcal {O}}}(1)$$

O
(
1
)

in future underground experiments, and the upcoming JUNO experiment in particular. The telltale signal providing a unique signature of such particles, would be a correlated sequence of three or more nuclear recoils along a straight line, corresponding to the motion of a non-relativistic ($$\beta \lesssim 10^{-2}$$

β
≲

10

-
2

) particle that could enter the detector from any direction. We provide some preliminary estimates for the expected event rates.
Observations of orbiting hot spots around scalarized Reissner–Nordström black holes
Authors: Chen Yiqian , Wang Peng , Yang Haitang
Published: March 2024

This paper investigates the observational signatures of hot spots orbiting scalarized Reissner–Nordström black holes, which have been reported to possess multiple photon spheres. In contrast to the single-photon sphere case, hot spots orbiting black holes with two photon spheres produce additional image tracks in time integrated images capturing a complete orbit of hot spots. Notably, these newly observed patterns manifest as a distinct second-highest peak in temporal magnitudes when observed at low inclination angles. These findings offer promising observational probes for distinguishing black holes with multiple photon spheres from their single-photon sphere counterparts.
Effect of tensile and compressive strains on the electronic structure of O-atom-doped monolayer MoS2
Authors: Jia-Xin Wang , Gui-Li Liu , Lin Wei , Gan Jiao , Guo-Ying Zhang
Published: March 2024

We investigate the effects of biaxial tensile and compressive strains on the electronic structure of O-doped monolayer MoS2 by density functional theory (DFT) in this paper. O-doped monolayer MoS2 is an exothermic reaction. The doping of O leads to the transformation of the system from direct bandgap to indirect, and the bonding of Mo and O causes a large amount of charge transfer. The application of tensile strain leads to a decrease in the stability of the doped system, and the system always maintains the nature of indirect bandgap. The degree of interatomic charge transfer and bandgap value gradually decrease with the increase of tensile strain. The application of compression strain improves the stability of the doped system, and as the compressive strain increases, the bandgap of the doped system completes the indirect–direct–indirect transformation. The bandgap value shows a trend of increasing and then decreasing. Additionally, the degree of charge transfer between atoms is strengthened.
Practical stability analysis of stochastic perturbed linear time-varying systems via integral inequality
Authors: Ezzine Faten
Published: March 2024

In this paper, we investigate the problem of stability of linear time-varying stochastic perturbed systems. We present sufficient conditions ensuring the global practical uniform exponential stability of a different class of stochastic perturbed systems based on generalized integral inequalities of Gronwall type. Finally, we provide numerical examples to prove the usefulness of the main results of this paper.
Development of Novel Hybrid Multi-Verse Optimizer with Sine Cosine Algorithm for Better Global Optimization
Authors: Son Pham Vu Hong , Trinh Nguyen Dang Nghiep
Published: March 2024

The sine cosine algorithm (SCA) and multi-verse optimizer (MVO) are the recognized optimization strategies frequently employed in numerous scientific areas. However, both SCA and MVO grapple with optimizing the transition between the exploitation and exploration mechanisms. Furthermore, MVO exhibits constraints in its exploitation capabilities. To tackle these limitations, this paper introduces a hybrid model termed SMVO, combining the advantages of both SCA and MVO. This hybrid approach seeks to harmonize exploitation and exploration stages by leveraging the unique advantages of each parent algorithm. The efficacy of SMVO was assessed using 23 benchmark test functions, revealing its competitive performance against not only SCA and MVO but also the ant lion optimization (ALO) and the dragonfly algorithm (DA). Additionally, SMVO’s applicability was further validated by successfully addressing three distinct engineering optimization challenges, underscoring its stability and promise as a global optimization tool.
NEM-GNN: DAC/ADC-less, Scalable, Reconfigurable, Graph and Sparsity-Aware Near-Memory Accelerator for Graph Neural Networks
Authors: Sundara Raman Siddhartha Raman , John Lizy , Kulkarni Jaydeep P.
Published: March 2024

Graph neural networks (GNNs) are of great interest in real-life applications such as citation networks and drug discovery owing to GNN’s ability to apply machine learning techniques on graphs. GNNs utilize a two-step approach to classify the nodes in a graph into pre-defined categories. The first step uses a combination kernel to perform data-intensive convolution operations with regular memory access patterns. The second step uses an aggregation kernel that operates on sparse data having irregular access patterns. These mixed data patterns render CPU/GPU-based compute energy-inefficient. Von Neumann based accelerators like AWB-GCN [
7
] suffer from increased data movement, as the data-intensive combination requires large data movement to/from memory to perform computations. ReFLIP [
8
] performs resistive random access memory based in-memory (PIM) compute to overcome data movement costs. However, ReFLIP suffers from increased area requirement due to dedicated accelerator arrangement, and reduced performance due to limited parallelism and energy due to fundamental issues in ReRAM-based compute. This article presents a scalable (non-exponential storage requirement), DAC/ADC-less PIM-based combination, with (i) early compute termination and (ii) pre-compute by reconfiguring SOC components. Graph and sparsity-aware near-memory aggregation using the proposed compute-as-soon-as-ready (CAR) broadcast approach improves performance and energy further. NEM-GNN achieves ∼80–230x, ∼80–300x, ∼850–1,134x, and ∼7–8x improvement over ReFLIP, in terms of performance, throughput, energy efficiency, and compute density.
Density Functional Theory Study of Lithiation and Sodiation in Sb2S3 and Sb2Se3 Anode Accompanying by S/Se Redox
Authors: Chakrabarti Shamik , Singh Arvind , Thakur A. K.
Published: March 2024

Density functional theory simulation has been performed to illuminate the mechanism of lithiation and sodiation in Sb2S3 and Sb2Se3 anodes which is accompanied by anionic S/Se redox. The lithiation and sodiation of Sb2S3 and Sb2Se3 is comprised of two steps, (a) conversion and (b) alloying -dealloying. During conversion Sb and alkaline (Li/Na) chalcogenides are formed. Voltages during the conversion reaction of lithiation and sodiation were ∼1.6 and ∼1.25 V, respectively, for both Sb2S3 and Sb2Se3. Comparison of X-ray absorption near edge spectroscopy imaging of S/Se as present in pristine chalcogenides and A2S/Se with A = Li/Na reflects the presence of S/Se redox, which is further confirmed by electronic charge density analysis. Sb acts as an active center for the second step alloying-dealloying reaction. The formation of alloy mainly occurs via formation of Li3Sb and Na3Sb, which exhibits redox peaks at 1.025 V for lithiation and 0.686 V for sodiation. As reported in earlier reports, the redox peak, at 0.95 V is found to appear due to the formation of alloy NaSb.
EMBRACE (Empowering Medical students’ skills in BReaking bAd news with Compassion and Empathy) module improves the skills of undergraduate medical students in effectively breaking the bad news: a case-control study
Authors: Arumugam Kaviya , Nandagopal Harshavardhini , Joseph Joseline , Balaji Jyotsna Needamangalam , Surapaneni Krishna Mohan
Published: March 2024

The Empowering Medical students’ skills in BReaking bAd news with Compassion and Empathy (EMBRACE) module is noteworthy for its holistic approach to training medical students in the delicate art of delivering distressing news to patients. It not only incorporates the evidence-based setting, perception, invitation, knowledge, emotions, and strategy (SPIKES) method but also distinguishes itself by providing real-life conversation examples and self-assessment cases, which make the training highly relatable and practical for students to actively engage in their learning and personal development.
TNIK depletion induces inflammation and apoptosis in injured renal proximal tubule epithelial cells
Authors: Bradford Shayna T. J. , Wu Haojia , Kirita Yuhei , Chen Changfeng , Malvin Nicole P. , Yoshimura Yasuhiro , Muto Yoshiharu , Humphreys Benjamin D.
Published: March 2024

The molecular drivers of successful and failed repair in the proximal tubule after acute kidney injury (AKI) are incompletely understood. We identified Traf2 and Nck interacting kinase ( Tnik) to be exclusively expressed in failed-repair proximal tubule cells after AKI. We tested the effect of si TNIK depletion in two proximal tubule cell lines followed by bulk RNA-sequencing analysis. Our results indicate that TNIK acts to suppress inflammatory signaling and apoptosis in injured renal proximal tubule epithelial cells to promote cell survival.
Peripheral vascular function in stroke: systematic review and meta-analysis
Authors: Bartsch Bria L. , Hazen Emily M. , Montgomery Robert N. , Trieu Calvin , Britton-Carpenter Amanda J. , Billinger Sandra A.
Published: March 2024

This systematic review and meta-analysis offers invaluable insight into poststroke vascular function. Despite the inherent heterogeneity among the 28 studies analyzed, we report that peripheral vascular dysfunction, as quantified by flow-mediated dilation, exists across all stages of stroke recovery. This finding underscores the importance for interventions that focus on improving vascular health and secondary stroke prevention.
Eccentric exercise ≠ eccentric contraction
Authors: Tecchio Paolo , Raiteri Brent J. , Hahn Daniel
Published: March 2024

Apparent eccentric exercises do not result in isolated eccentric contractions, but shortening-stretch contractions at the fascicle level. The amount of fascicle shortening and stretch depends on the preactivation during the exercise and cannot be estimated from the muscle-tendon unit (MTU) or joint kinematics. As different fascicle mechanics might trigger different adaptations to eccentric exercise, muscle-tendon unit series compliance and muscle preactivation need to be considered when eccentric exercise protocols are designed.
Does Treatment with Sodium‐Glucose Cotransporter‐2 Inhibitors Affect Adherence to International Society Criteria for Diabetic Ketoacidosis in Adult Patients with Type 2 Diabetes? A Retrospective Cohort Analysis
Authors: O’Brolchain Aongus , Maletsky Joshua , Mian Ibrahim , Edwards Serena
Published: March 2024

Objective(s). Diabetic ketoacidosis (DKA) is a rare but well‐known complication of sodium‐glucose transporter inhibitor (SGLT2i) treatment in patients with type 2 diabetes. The physiological effects of SGLT2i are such that hyperglycaemia and ketonuria are no longer reliable diagnostic tools in patients treated with this class of medication. Diagnostic criteria for DKA varies between major society guidelines. The Joint British Diabetes Society (JBDS) and American Association of Clinical Endocrinology/American College of Endocrinology (AACE/ACE) have recently made changes to their diagnostic criteria to account for the effects of SGTL2i. This study sought to investigate whether treatment with SGLT2i might result in overdiagnosis of DKA and less adherence to the international diagnostic guidelines in hospitalised patients with type 2 diabetes treated with SGLT2i. Additionally, the demographics and clinical characteristics of patients with type 2 diabetes presenting with DKA were compared based on their treatment with SGLT2i at the time of diagnosis. Design. Retrospective observational study. Setting. Inpatients at two teaching hospitals in Queensland, Australia. Primary Outcome Measure(s). The number of patients meeting the Joint British Diabetes Society (JBDS) and American Association of Clinical Endocrinology/American College of Endocrinology (AACE/ACE) diagnostic criteria for DKA. Patients were divided into two groups by treatment with SGLT2i at the time of diagnosis. Participants. Adult patients (>18 years old) with type 2 diabetes diagnosed with DKA from April 2015 to January 2022. Patients without type 2 diabetes were excluded. Results. One hundred and sixty‐five patients were included in this study—comprising 94 patients in the SGLT2i cohort and 70 in the non‐SGLT2i cohort. A significantly smaller proportion of patients in the SGLT2i vs. non‐SGLT2i cohorts met both JBDS (56% vs. 72%, p = 0.035) and AACE/ACE (63% vs. 82%, p = 0.009) criteria for diagnosis of DKA. Conclusion. Patients with type 2 diabetes treated with SGLT2i may be more likely to be diagnosed with DKA despite not meeting the criteria. Despite recent adjustments to account the physiological effects of SGLT2i, significant variation in criteria between major society guidelines presents ongoing challenges to clinicians. The proportion of patients diagnosed using both JDBS and AACE/ACE were comparable, suggesting a reasonable degree of agreement.
A Potentially Ecosustainable Hazelnut/Carob-Based Spread
Authors: Principato Laura , Carullo Daniele , Gruppi Alice , Duserm Garrido Guillermo , Giuberti Gianluca , Lambri Milena , Spigno Giorgia , Bassani Andrea
Published: March 2024

Commercial cocoa and hazelnut-based sweet spreads typically present a poor nutribiochemical level due to their ingredients and recipes, while nowadays, there is the need of developing sustainable food products addressing both an improved nutritional and environmental profile. The aim of this work was then to develop an innovative hazelnut/carob-based spread with potential high sustainability and nutritional profile, including the exploitation of grape-processing residues (grape skin flour and grapeseed oil) and carob pulp as cocoa surrogate. Rheological (rotational/oscillatory), oxidative, and thermal features of the spread were assessed and compared with two commercial nut-cocoa-based products. Tribology was used to mimic and evaluate the spreads’ behavior during oral consumption, and sensory profile (by quantitative descriptive analysis) was also assessed. All products exhibited a pseudoplastic behavior, with the elastic component prevailing over the viscous one. The innovative product showed the highest lubricity from both rheological and sensory analysis, thus well correlating to the obtained lowest viscosity and friction factor trends. Grapeseed oil provided a better nutritional profile, but the largest amount of unsaturated fatty acids promoted oxidation, despite the higher total phenolic content and antioxidant capacity coming from the use of carob and grape skin powders. The sensory perception investigation revealed a characteristic mouthfeel/flavor for the new spread identified having a more fluid consistency and a bitter/sour taste, together with a greater stickiness and a poorer smoothness due to a higher fiber content and solid fat absence.
Effect of Ghee Residue Powder and Pearl Millet Flour Substitution on Rheological, Textural, and Sensorial Characteristics of Eggless Muffin
Authors: G M Vinay , Singh A. K.
Published: March 2024

Bakery products are becoming an essential part of the human diet. Millets are the staple grains in Asia and African countries, and they are the super future food because of their nutritive and disease-preventive nature. Pearl millet is one of the most nutritious cereal grains, and its protein lacks gluten, which makes it a suitable base material for the preparation of gluten-free products. However, gluten is necessary because of its unique viscoelastic nature, which makes the most innovative bakery items. In this study, 50% refined wheat flour (RWF) has been replaced with pearl millet flour (PMF) to prepare a muffin, and a ghee residue is utilized to make a ghee residue powder (GRP) as a functional ingredient to replace whey protein concentrate (WPC) in the eggless muffin. Substitution of fat with GRP reduced the specific gravity of batter from 1.05 to 0.99; lightness value was considerably decreased, whereas the redness and yellowness values increased from 1.06 to 8.32 and 23.62 to 26.20, respectively. Replacement of RWF with PMF affected the lightness and specific gravity of the batter. Substitution with PMF and GRP reduced the viscosity from 13.83 Pa·s to7.08 Pa·s. Gelatinization temperature of batters varied with substitution of flour and fat with PMF and GRP. Muffin volume dramatically decreased from 56.19 to 36.84 cm3 with substitution of GRP and PMF. Weight loss was increased from 12.14 to 13.68% by substitution. The hardness and springiness were reduced with substitution. The GRP can replace fat up to 25%; thereafter, muffin’s quality characteristic reduces; hence, 50% PMF and 25% GRP combination give satisfiable muffin product.
An Aloe‐Based Composition Constituting Polysaccharides and Polyphenols Protected Mice against D‐Galactose‐Induced Immunosenescence
Authors: Yimam Mesfin , Horm Teresa , O’Neal Alexandria , Jiao Ping , Hong Mei , Jia Qi
Published: March 2024

A decline in immune response, exhibited in the form of immunosenescence and inflammaging, is an age‐associated disturbance of the immune system known to predispose the elderly to a greater susceptibility to infection and poor vaccine response. Polysaccharides and polyphenols from botanicals are known for their immune modulation effects. Here we evaluated a standardized mushroom‐based composition, UP360, from Aloe barbadensis, Poria cocos, and Rosmarinus officinalis, as a natural nutritional supplement for a balanced immune response in an accelerated aging mouse model. Immunosenescence was induced by continual subcutaneous injection of D‐galactose (D‐gal) at a dose of 500 mg/kg/day to CD‐1 mice. UP360 was administered at oral doses of 200 and 400 mg/kg to the mice starting on the 5th week of D‐gal injection. The study lasted for a total of 9 weeks. All mice were given a quadrivalent influenza vaccine at 3 µg/animal via intramuscular injection 14 days before the end of the study. A group of D‐gal‐treated mice treated at 400 mg/kg/day UP360 was kept without vaccination. Whole blood, serum, spleen homogenate, and thymus tissues were used for analysis. UP360 was found to improve the immune response as evidenced by stimulation of innate and adaptive immune responses, increase antioxidant capacity as reflected by augmented SOD and Nrf2, and preserve vital immune organs, such as the thymus, from aging‐associated damage. The findings depicted in this report show the effect of the composition in activating and maintaining homeostasis of the immune system both during active infections and as a preventive measure to help prime the immune system. These data warrant further clinical study to explore the potential application of the mushroom‐based composition as an adjunct nutritional supplement for a balanced immune response.
A Novel SMFL‐Based Assessment Method for Corrosion Nonuniformity of Rebar and Its Application in Reliability Analysis of Corroded RC Beam
Authors: Qiu Junli , Jing Yue , Zhang Weiping , Jiang Chao
Published: March 2024

The reliability of corroded reinforced concrete (RC) structures relies on the accurate minimum cross‐sectional area of corroded rebar. In this study, the accurate morphologies and self‐magnetic flux leakage (SMFL) field strengths of twenty‐eight non‐uniformly corroded rebars were obtained using 3D structural light scanning and micromagnetic detection technologies, based on which three indices of the SMFL field variation ratio dH, the corrosion non‐uniformity degree dSn, and the cross‐sectional area ratio K0.25 are proposed. The statistical results show that the probability densities of dSn and K0.25 obey the Weibull distribution and Gamma distribution at the 95% confidence level, respectively, and their distribution parameters are linearly or inversely proportional to dH. The probability density distribution of the minimum cross‐sectional area of corroded rebar can be determined using indices dSn and K0.25, based on which a feasible SMFL‐based reliability assessment method of corroded RC structures is proposed. The case study of a real specific corroded RC beam shows that the reliability assessment error of the SMFL‐based method is only 1.2%, which is much lower than the 20.7% error of the existing method. This SMFL‐based method provides a novel idea that can automatically and accurately assess the effect of rebars’ corrosion non‐uniformity on the reliability of specific in‐serviceRC structures.
White Dot Syndromes: Report of Three Cases
Authors: Olazaran Leire , Jiménez Ana , González de los Mártires Pablo , Guerrero Gonzalo , Gangoitia Nerea , Salmeron Iñigo , Galarza Ane , Argüelles Ana Sofía , Elso Beatriz , Reyzabal Irene , Compains Esther , Heras Henar , López Santiago
Published: March 2024

Introduction: The term white dot syndromes has been used to refer conditions that differ in their morphology and prognosis. We report three cases of different pathologies encompassed within the white dot syndromes. Case Presentations: Case 1: A 26-year-old female presented with scotoma in her right eye. Fundus examination revealed multiple white dots that demonstrated early hyperfluorescence with late staining on FA. OCT showed discontinuities in inner segment-outer segment junction associated with columnar-shaped outer retinal hyperreflective bands. AF revealed multiple hyperautofluorescent dots around the posterior pole, compatible with multiple evanescent white dot syndrome. The symptoms improved without treatment. Case 2: A 16-year-old male presented with retinal lesions compatible with punctate inner choroidopathy in his right eye. OCT showed lesion in the outer retinal layer. FAF revealed parafoveal hypoautofluorescent dots with early hyperfluorescence and late staining on FFA. After oral corticotherapy, they progress to atrophic scars. Case 3: A 65-year-old male presented with scotoma and decreased vision in his right eye. OCT showed hyperreflectivity in the outer layer that progresses to a large atrophic plaque with foveal affectation. FAF demonstrated hyperautofluorescent placoid lesion occupying macular area, compatible with acute posterior multifocal placoid pigment epitheliopathy. Retinal lesions improved with systemic corticosteroids. Conclusion: The FAF pattern helps know the distribution of the lesions. It represents a noninvasive method that has been shown to be useful in the diagnosis and monitoring of white dot syndromes.
Las Políticas Educativas Rurales en Colombia 1990- 2018
Authors: Bohórquez Forero Juan Pablo
Published: March 2024

El presente artículo de reflexión tiene un doble objetivo. En primer lugar, se busca hacer un recorrido por las principales políticas educativas del sector rural en el periodo comprendido de 1990 a 2018, y, en segundo lugar, se pretende analizar cuáles han sido las principales tendencias de dichas políticas. Metodológicamente, se utilizó el análisis documental para la revisión de las políticas públicas; los datos fueron transcritos y categorizados, lo que facilitó el análisis de contenido. El artículo caracteriza dos tendencias fundamentales: políticas de cobertura y políticas economicistas. Las primeras buscan flexibilizar el servicio educativo para llegar a las comunidades más vulnerables y apartadas del país; mientras que las segundas buscan activar el sector rural para que sea más competitivo económicamente. Se concluye que las políticas educativas rurales tienen una idea parcializada del campo colombiano y no han representado cambios significativos
Zebrafish ApoB-Containing Lipoprotein Metabolism: A Closer Look
Authors: Moll Tabea O.C. , Farber Steven A.
Published: March 2024

Zebrafish have become a powerful model of mammalian lipoprotein metabolism and lipid cell biology. Most key proteins involved in lipid metabolism, including cholesteryl ester transfer protein, are conserved in zebrafish. Consequently, zebrafish exhibit a human-like lipoprotein profile. Zebrafish with mutations in genes linked to human metabolic diseases often mimic the human phenotype. Zebrafish larvae develop rapidly and externally around the maternally deposited yolk. Recent work revealed that any disturbance of lipoprotein formation leads to the accumulation of cytoplasmic lipid droplets and an opaque yolk, providing a visible phenotype to investigate disturbances of the lipoprotein pathway, already leading to discoveries in MTTP (microsomal triglyceride transfer protein) and ApoB (apolipoprotein B). By 5 days of development, the digestive system is functional, making it possible to study fluorescently labeled lipid uptake in the transparent larvae. These and other approaches enabled the first in vivo description of the STAB (stabilin) receptors, showing lipoprotein uptake in endothelial cells. Various zebrafish models have been developed to mimic human diseases by mutating genes known to influence lipoproteins (eg,
ldlra
,
apoC2
). This review aims to discuss the most recent research in the zebrafish ApoB-containing lipoprotein and lipid metabolism field. We also summarize new insights into lipid processing within the yolk cell and how changes in lipid flux alter yolk opacity. This curious new finding, coupled with the development of several techniques, can be deployed to identify new players in lipoprotein research directly relevant to human disease.
Circadian and Diurnal Regulation of Cerebral Blood Flow
Authors: Webb Alastair J.S. , Klerman Elizabeth B. , Mandeville Emiri T.
Published: March 2024

Circadian and diurnal variation in cerebral blood flow directly contributes to the diurnal variation in the risk of stroke, either through factors that trigger stroke or due to impaired compensatory mechanisms. Cerebral blood flow results from the integration of systemic hemodynamics, including heart rate, cardiac output, and blood pressure, with cerebrovascular regulatory mechanisms, including cerebrovascular reactivity, autoregulation, and neurovascular coupling. We review the evidence for the circadian and diurnal variation in each of these mechanisms and their integration, from the detailed evidence for mechanisms underlying the nocturnal nadir and morning surge in blood pressure to identifying limited available evidence for circadian and diurnal variation in cerebrovascular compensatory mechanisms. We, thus, identify key systemic hemodynamic factors related to the diurnal variation in the risk of stroke but particularly identify the need for further research focused on cerebrovascular regulatory mechanisms.
Circadian Regulation of Cardiac Arrhythmias and Electrophysiology
Authors: Delisle Brian P. , Prabhat Abhilash , Burgess Don E. , Ono Makoto , Esser Karyn A. , Schroder Elizabeth A.
Published: March 2024

Circadian rhythms in physiology and behavior are ≈24-hour biological cycles regulated by internal biological clocks (ie, circadian clocks) that optimize organismal homeostasis in response to predictable environmental changes. These clocks are present in virtually all cells in the body, including cardiomyocytes. Many decades ago, clinicians and researchers became interested in studying daily patterns of triggers for sudden cardiac death, the incidence of sudden cardiac death, and cardiac arrhythmias. This review highlights historical and contemporary studies examining the role of day/night rhythms in the timing of cardiovascular events, delves into changes in the timing of these events over the last few decades, and discusses cardiovascular disease-specific differences in the timing of cardiovascular events. The current understanding of the environmental, behavioral, and circadian mechanisms that regulate cardiac electrophysiology is examined with a focus on the circadian regulation of cardiac ion channels and ion channel regulatory genes. Understanding the contribution of environmental, behavioral, and circadian rhythms on arrhythmia susceptibility and the incidence of sudden cardiac death will be essential in developing future chronotherapies.
Circadian Rhythms in Cardiovascular Metabolism
Authors: Lal Hind , Verma Suresh Kumar , Wang Yajing , Xie Min , Young Martin E.
Published: March 2024

Energetic demand and nutrient supply fluctuate as a function of time-of-day, in alignment with sleep-wake and fasting-feeding cycles. These daily rhythms are mirrored by 24-hour oscillations in numerous cardiovascular functional parameters, including blood pressure, heart rate, and myocardial contractility. It is, therefore, not surprising that metabolic processes also fluctuate over the course of the day, to ensure temporal needs for ATP, building blocks, and metabolism-based signaling molecules are met. What has become increasingly clear is that in addition to classic signal-response coupling (termed reactionary mechanisms), cardiovascular-relevant cells use autonomous circadian clocks to temporally orchestrate metabolic pathways in preparation for predicted stimuli/stresses (termed anticipatory mechanisms). Here, we review current knowledge regarding circadian regulation of metabolism, how metabolic rhythms are synchronized with cardiovascular function, and whether circadian misalignment/disruption of metabolic processes contribute toward the pathogenesis of cardiovascular disease.
Stroke in the Time of Circadian Medicine
Authors: Mergenthaler Philipp , Balami Joyce S. , Neuhaus Ain A. , Mottahedin Amin , Albers Gregory W. , Rothwell Peter M. , Saver Jeffrey L. , Young Martin E. , Buchan Alastair M.
Published: March 2024

Time-of-day significantly influences the severity and incidence of stroke. Evidence has emerged not only for circadian governance over stroke risk factors, but also for important determinants of clinical outcome. In this review, we provide a comprehensive overview of the interplay between chronobiology and cerebrovascular disease. We discuss circadian regulation of pathophysiological mechanisms underlying stroke onset or tolerance as well as in vascular dementia. This includes cell death mechanisms, metabolism, mitochondrial function, and inflammation/immunity. Furthermore, we present clinical evidence supporting the link between disrupted circadian rhythms and increased susceptibility to stroke and dementia. We propose that circadian regulation of biochemical and physiological pathways in the brain increase susceptibility to damage after stroke in sleep and attenuate treatment effectiveness during the active phase. This review underscores the importance of considering circadian biology for understanding the pathology and treatment choice for stroke and vascular dementia and speculates that considering a patient’s chronotype may be an important factor in developing precision treatment following stroke.