bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality monitoring and control for plasticization of acrylonitrile‐butadiene‐styrene regrind polymer in injection molding
Authors: Chen Jian‐Yu , Wong Liang‐Ci , Huang Ming‐Shyan
Published: December 2023

To meet net‐zero carbon emissions in injection molding, it is desirable to use regrind polymers in plastic parts fabrication. However, the quality of regrind polymer differs from virgin polymer due to the effects of temperature, pressure, and shear stress in the prior molding process. Consequently, the molded components differ in quality compared to those made from virgin material. This study investigates the feasibility of enhancing the quality consistency of regrind plastic components by controlling melt quality in plasticization. The evaluation of melt quality involves extracting two quality metrics from the pressure signal (i.e., the peak pressure and the pressure integral). They are then used to adjust the plasticization parameters as required to ensure that the weight and dimensions of the final regrind parts approach those of parts produced using virgin polymer. The experimental results show that the pressure integral effectively indicates the quality variation of the molded part during the injection molding of regrind polymer. Notably, by adjusting the back pressure, the quality of the molded part closely resembles that of the part made from virgin feedstock after six shots.
Extended detailed balance modeling toward solar cells with cement‐based radiative coolers
Authors: Cagnoni Matteo , Testa Pietro , Dolado Jorge S. , Cappelluti Federica
Published: December 2023

Reducing the temperature of a solar cell increases its efficiency and lifetime. This can be achieved by radiative cooling, a passive and simple method relying on materials that dump heat into outer space by thermal emission within the atmosphere transparency window between 8 and
. As most radiative coolers are expensive or possibly UV unstable, we have recently proposed cement‐based solutions as a robust and cost‐effective alternative. However, the assessment model used describes the cell in the radiative limit and with perfect thermal coupling to the cooler, in line with the literature. In this work, we lift these two approximations, by incorporating Auger and Shockley–Read–Hall nonradiative recombination and a finite heat transfer coefficient at the cell/cooler interface, to obtain a thermal description of the cell/cooler stack closer to reality, while preserving the universality and transparency of the detailed‐balance approach. We use this model to demonstrate that the cell performance gains provided by a radiative cooler are underestimated in the radiative limit and are hence more prominent in devices with stronger nonradiative recombination. Furthermore, we quantify the relation between cell temperature and heat transfer coefficient at the cell/cooler interface and show how this can be used to define design requirements. The extended model developed, and the resulting observations provide important guidelines toward the practical realization of novel radiative coolers for solar cells, including cement‐based ones.
Targeted improvement of plant‐based protein: Genome‐wide association mapping of a lentil (Lens culinaris Medik.) diversity panel
Authors: Johnson Nathan , Boatwright J. Lucas , Bridges William , Thavarajah Pushparajah , Kumar Shiv , Thavarajah Dil
Published: December 2023

Societal Impact Statement

The world is increasingly looking to plant‐based sources to meet its protein needs. Multiple factors are driving this progression, ranging from nutritional and ethical considerations to climate change and population growth. As a pulse crop, lentil is ideal to help meet this change in demand. However, plant‐based proteins have limiting amino acids and lower protein digestibility compared to animal‐based proteins. This research identifies genetic markers that can be used to accelerate breeding of protein quality traits in lentil to ultimately help meet the rising demand in high‐quality plant‐based protein and bolster global food and nutritional security.

Lentil (Lens culinaris Medik.) contains ~25% high‐quality protein in addition to high concentrations of prebiotic carbohydrates and micronutrients, such as folate, iron, zinc, and selenium. As animal‐based protein's economic and environmental costs rise, plant‐based protein sources, such as lentil, will become increasingly important to global food systems. Consequently, evaluating and targeting protein quality traits for genomic‐assisted breeding is a valuable objective for lentil breeding programs.

A diversity panel of 183 breeding lines was analyzed for protein quality traits, including amino acids and protein digestibility. Genotyping‐by‐sequencing (GBS) data were used to assess population structure and conduct genome‐wide association studies (GWAS). Genes in local linkage disequilibrium (LD) with significant single nucleotide polymorphism (SNP) markers were identified and categorized by homology.

Protein quality traits showed a wide range of variation. Repeatability estimates were low to moderate across traits. Twelve traits were strongly correlated with each other (r > .7). Admixture analysis identified six ancestral subpopulations, which also demonstrated clustering in principal component analysis. Ten different traits had significant SNP associations; two loci were shared across multiple traits. Twenty‐seven candidate genes, including glutathione S‐transferase, protease family, and gibberellin 2‐beta‐dioxygenase genes, were identified.

This paper identifies SNP markers associated with lentil protein quality traits. Once validated, these SNPs could accelerate lentil protein quality breeding efforts. By targeting lentil's limiting amino acids (methionine and cysteine) and protein digestibility through marker‐assisted selection, the nutritional value of lentil's protein content could be increased without the need to alter total protein content.
Evidence of direct interaction between cisplatin and the caspase‐cleaved prostate apoptosis response‐4 tumor suppressor
Authors: Raut Krishna K. , Pandey Samjhana , Kharel Gyanendra , Pascal Steven M.
Published: December 2023

Prostate apoptosis response‐4 (Par‐4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par‐4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase‐cleaved Par‐4 (cl‐Par‐4) fragment and cisplatin. Additionally, elemental analysis was conducted to quantitatively assess the binding of cisplatin to the protein, utilizing inductively coupled plasma‐optical emission spectroscopy and atomic absorption spectroscopy. Our findings provide evidence of direct interaction between cl‐Par‐4 and cisplatin, and reveal a binding stoichiometry of 1:1. This result provides insights that could be useful in enhancing the efficacy of cisplatin‐based and tumor suppressor‐based cancer therapies.
Quantitative delineation of water sources in the river Ganga using stable water isotopes
Authors: Kumar Anurag , Basu Sayak , Ajay Ajay , Jha Deepak Kumar , Sanyal Prasanta
Published: December 2023

Quantitative delineation of water sources in a large river system is essential for the sustainable use of water. In the present study, we have tested two different methodologies to estimate the contribution from different water sources in the river Ganga. The first model uses stable isotopes and physicochemical parameters of water to delineate the contribution of glacier‐melt, groundwater, and surface runoff in different stretches of the river Ganga. The end member‐based mixing model provides glacier‐melt contribution of ~31.2%, ~5.5%, and ~0.5% in the upper, middle, and lower stretch of the river Ganga. The model showed maximum contribution from groundwater (~66.3%) in the middle stretch and surface runoff (~57.2%) in the lower stretch of the river Ganga. However, the uncertainties in the estimates from the three‐component mixing model were significantly high due to temporal variability in the end member values. To provide estimates with lower uncertainty, an alternate method (discharge dependent budget estimation [DDBE]) has been proposed which delineates the contribution of groundwater and surface runoff in small segments of the river. The DDBE model confines the calculation for budget estimates to smaller segments of the river and hence leads to lower uncertainties in the results, providing improved systematic estimation of water budget for large river systems. In the present study, estimates from the DDBE model suggest that groundwater contributes ~79% of the additional water whereas the contribution from surface runoff is ~21% in the middle and lower stretch of the river Ganga. The DDBE model was successfully applied in 5 small segments along the stretch of the river Ganga and the methodology used shows great potential for systematic delineation of water sources in large river system.
Investigating the role of entrepreneurship in advancing renewable energy for sustainable development: Evidence from a System‐GMM panel data approach
Authors: Karimi Mohammad Sharif , Doostkouei Saleh Ghavidel , Shaiban Mohammed , Easvaralingam Yalini , Khan Yousaf Ali
Published: December 2023

Entrepreneurship serves as a driving force for the advancement of renewable energy. Entrepreneurs are often at the forefront of innovation, bringing new technologies and business models to the clean energy sector. This study conducts a comprehensive examination of the intricate relationship between entrepreneurship and renewable energy production in 23 developed countries throughout the period from 2000 to 2020. For this purpose, the impact of 11 sub‐index of entrepreneurship on renewable energy production has been estimated. The method is dynamic panel data with the system GMM (Generalized Method of Moments) technique. After estimating 11 entrepreneurship sub‐indices effects separately on renewable energy production, the impact of each is ranked. The findings showed that the impact rank of 11 sub‐indexes of entrepreneurship on renewable energy production is as follows: Commercial and professional infrastructure (CP), R&D transfer (RD), Physical and services infrastructure (PS), Governmental support and policies (GS), Taxes and bureaucracy (TB), Governmental programs (GP), Internal market openness (MO), Internal market dynamics (MD), Post‐school entrepreneurial education and training (PE), Basic school entrepreneurial education and training (BE), and Cultural and social norms (CS). The importance of Commercial and professional infrastructure (CP) as an entrepreneurship sub‐indices is 2 times more than R&D transfer (RD), so Commercial and professional infrastructure is vital for the development of entrepreneurship that affects the production of renewable energies. This study not only underscores the central role of entrepreneurship in driving the adoption of renewable energy but also provides essential insights into key policy measures to accelerate the transition to sustainable energy sources. It highlights the urgency of addressing environmental challenges and emphasizes the imperative for collaboration among governments, NGOs, and educational institutions to achieve these critical goals.
Infrabanking: Mobilizing capital in communist Cuba
Authors: Wig Ståle
Published: December 2023

In 2011, the Cuban government authorized banks to start offering loan credit to the country's growing number of small businesses for the first time since the beginning of the revolution. Yet in the following years, citizens have largely circumvented these services. This article draws on twenty months of fieldwork among market traders in Havana to examine why so few Cubans rely on the formal banking system to secure capital. It analyzes alternative methods people employ to organize their financial futures, by leveraging kinship ties, partnerships, friendships, property, and loan sharks, and by participating in rotating savings and credit associations. To understand the advantages these approaches offer to mobilize capital, it is crucial to grasp how people navigate their economic lives in ways that are influenced but not dictated by short‐term considerations of net profit. Nonmonetary concerns about access, time frame, and visibility lead people to raise and store wealth outside the formal banking system, constituting a domain I call infrabanking: banking practices that are too far removed from the established assumptions about banking to be perceived as part of the same phenomenon.
Estimations of value in “Belgrade's Amazonia”
Authors: Kojanić Ognjen
Published: December 2023

In this article, I analyze the arguments marshaled in favor of and against the project to build a new port on the Danube River in the wetland area popularly referred to as Belgrade's Amazonia. Building on scholarship on ascribing value to infrastructures and the environment, I use the term estimation to highlight ambiguity in the process of ongoing and open‐ended valuation. Estimation denotes a rough determination of value, a process of valuation based on approximation rather than measurement or enumeration. In estimations articulated by disparate social actors in this case, various economic and socioenvironmental values sometimes clashed, sometimes blended with one another. The flexibility in the use of registers of value enabled contradictory outcomes: a coalition was formed to protect Belgrade's Amazonia despite the heterogeneous arguments against the project, and later, the project's critique was co‐opted by the government. Estimations are fundamentally open to opportunistic political uses owing to their malleability, with implications for the politics of valuation with regard to infrastructures and environmental protection more broadly.
Enhanced Ion Transport Through Mesopores Engineered with Additional Adsorption of Layered Double Hydroxides Array in Alkaline Flow Batteries
Authors: Wang Pengfei , Zhang Kun , Li Hao , Hu Jing , Zheng Menglian
Published: December 2023

Efficient mass transfer in electrodes is essential for the electrochemical processes of battery charge and discharge, especially at high rates and capacities. This study introduces a 3D electrode design featuring layered double hydroxides (LDHs) nanosheets array grown in situ on a carbon felt surface for flow batteries. The mesoporous structure and surface characteristic of LDH nanosheets, especially, the hydroxyl groups forming a unique “H‐bonding‐like” geometry with ferrous cyanide ions, facilitate efficient adsorption and ion transport. Thus, the designed LDHs electrode enables the alkaline zinc‐iron flow battery to maintain a voltage efficiency of 81.6% at an ultra‐high current density of 320 mA cm−2, surpassing the values reported in previous studies. The energy efficiency remains above 84% after 375 cycles at a current density of 240 mA cm−2. Molecular dynamics simulations verify the enhanced adsorption effect of LDH materials on active ions, thus facilitating ion transport in the battery. This study provides a novel approach to improve mass transport in electrodes for alkaline flow batteries and other energy storage devices.
The design and synthesis of Prussian blue analogs as a sustainable cathode for sodium‐ion batteries
Authors: Fan Siwei , Liu Yijie , Gao Yun , Liu Yang , Qiao Yun , Li Li , Chou Shu‐Lei
Published: December 2023

Sodium‐ion batteries (SIBs) present great appeal in various energy storage systems, especifically for stationary grid storage, on account of the abundance of sources and low cost. Unfortunately, the commercialization of SIBs is mainly limited by available electrode materials, especially for the cathodes. Prussian blue analogs (PBAs), emerge as a promising alternative for their structural feasibility in the application of SIBs. Decreasing the defects (vacancies and coordinated water) is an effective strategy to achieve superior electrochemical performance during the synthetic processes. Herein, we summarize crystal structures, synthetic methods, electrochemical mechanisms, and the influences of synthesis conditions of PBAs in detail. This comprehensive overview on the current research progresses of PBAs will give guides and directions to solve the existing problems for their application in SIBs.
Cadmium‐induced global DNA hypermethylation promoting mitochondrial dynamics dysregulation in hippocampal neurons
Authors: Geng Huixia , An Qihang , Song Jie , He Dongling , Han Huimin , Wang Lai
Published: December 2023

Environmental cadmium exposure during pregnancy or adolescence can cause neurodevelopmental toxicity, lead to neurological impairment, and reduce cognitive abilities, such as learning and memory. However, the mechanisms by which cadmium causes neurodevelopmental toxicity and cognitive impairment are still not fully elucidated. This study used hippocampal neurons cultured in vitro to observe the impact of cadmium exposure on mitochondrial dynamics and apoptosis. Exposure to 5 μM cadmium causes degradation of hippocampal neuron cell bodies and axons, morphological destruction, low cell viability, and apoptosis increase. Cadmium exposure upregulates the expression of mitochondrial fission proteins Drp1 and Fis1, reduces the expression of mitochondrial fusion‐related proteins MFN1, MFN2, and OPA1, as well as reduces the expression of PGC‐1a. Mitochondrial morphology detection demonstrated that cadmium exposure changes the morphological structure of mitochondria in hippocampal neurons, increasing the number of punctate and granular mitochondria, reducing the number of tubular and reticular mitochondria, decreasing mitochondrial mass, dissipating mitochondrial membrane potential (ΔΨm), and reducing adenosine triphosphate (ATP) production. Cadmium exposure increases the global methylation level of the genome and upregulates the expression of DNMT1 and DNMT3α in hippocampal neurons. 5‐Aza‐CdR reduces cadmium‐induced genome methylation levels in hippocampal neurons, increases the number of tubular and reticular mitochondria, and promotes cell viability. In conclusion, cadmium regulates the expression of mitochondrial dynamics‐related proteins by increasing hippocampal neuron genome methylation, changing mitochondrial morphology and function, and exerting neurotoxic effects.
Curcumin attenuates diphenyl phosphate‐induced apoptosis in GC‐2spd(ts) cells through activated autophagy via the Nrf2/P53 pathway
Authors: Wei Lai , Li Siwen , Ma Yu , Ye Shuzi , Yuan Yu , Zeng Yuan , Raza Tausif , Xiao Fang
Published: December 2023

Diphenyl phosphate (DPhP) is one of the frequently used derivatives of aryl phosphate esters and is used as a plasticizer in industrial production. Like other plasticizers, DPhP is not chemically bound and can easily escape into the environment, thereby affecting human health. DPhP has been associated with developmental toxicity, reproductive toxicity, neurodevelopmental toxicity, and interference with thyroid homeostasis. However, understanding of the underlying mechanism of DPhP on the reproductive toxicity of GC‐2spd(ts) cells remains limited. For the first time, we investigated the effect of DPhP on GC‐2spd(ts) cell apoptosis. By decreasing nuclear factor erythroid‐derived 2‐related factor (Nrf2)/p53 signaling, DPhP inhibited autophagy and promoted apoptosis. DPhP reduced total antioxidant capacity and nuclear Nrf2 and its downstream target gene expression. In addition, we investigated the protective effects of Curcumin (Cur) against DPhP toxicity. Cur attenuated the DPhP‐induced rise in p53 expression while increasing Nrf2 expression. Cur inhibited DPhP‐induced apoptosis in GC‐2spd(ts) cells by activating autophagy via Nrf2/p53 signaling. In conclusion, our study provides new insights into the reproductive toxicity hazards of DPhP and demonstrates that Cur is an important therapeutic agent for alleviating DPhP‐induced reproductive toxicity by regulating Nrf2/p53 signaling.
Flat from anti de Sitter
Authors: Campoleoni Andrea , Delfante Arnaud , Pekar Simon , Petropoulos P. Marios , Rivera-Betancour David , Vilatte Matthieu
Published: December 2023

Abstract

Ricci-flat solutions to Einstein’s equations in four dimensions are obtained as the flat limit of Einstein spacetimes with negative cosmological constant. In the limiting process, the anti-de Sitter energy-momentum tensor is expanded in Laurent series in powers of the cosmological constant, endowing the system with the infinite number of boundary data, characteristic of an asymptotically flat solution space. The governing flat Einstein dynamics is recovered as the limit of the original energy-momentum conservation law and from the additional requirement of the line-element finiteness, providing at each order the necessary set of flux-balance equations for the boundary data. This analysis is conducted using a covariant version of the Newman-Unti gauge designed for taking advantage of the boundary Carrollian structure emerging at vanishing cosmological constant and its Carrollian attributes such as the Cotton tensor.
Non-invertible symmetries and RG flows in the two-dimensional O(n) loop model
Authors: Jacobsen Jesper Lykke , Saleur Hubert
Published: December 2023

Abstract

In a recent paper, Gorbenko and Zan [1] observed that O(n) symmetry alone does not protect the well-known renormalization group flow from the dilute to the dense phase of the two-dimensional O(n) model under thermal perturbations. We show in this paper that the required “extra protection” is topological in nature, and is related to the existence of certain non-invertible topological defect lines. We define these defect lines and discuss the ensuing topological protection, both in the context of the O(n) lattice model and in its recently understood continuum limit, which takes the form of a conformal field theory governed by an interchiral algebra.
Sinus pilonidalis—elastic ligature as an optimal outpatient treatment
Authors: Danihel Ľudovít , Černý Marián , Rajčok Matúš , Mosná Kristína , Bou Ezzeddine Jihad , Dropco Ivor , Schnorrer Milan
Published: December 2023

Background

The incidence of pilonidal sinus shows a steadily rising tendency, especially in the patient age group of up to 40 years. Treatment of this condition is often protracted involving lengthy sick leave and an increased risk of recurrence. The optimal treatment of pilonidal sinus remains open to debate, but it should focus on decreasing the length of hospitalization, promoting a rapid return to daily life, maintaining low pain levels, and keeping costs at a minimum.

Materials and methods

In our study conducted between 2017 and 2021, we focused on treatment of pilonidal sinus. We performed 50 elastic ligature procedures with a median observation time of 30 months. The patients were divided into three groups according to the characteristics of pilonidal sinus: (1) acute primary abscess; (2) acute recurrent abscess; and (3) chronic fistula.

Results

Out of a total of 50 patients with a subsequent 30-month follow-up, we observed complete recovery in 47 patients and recurrence in three patients. Return to work was possible immediately after the operation, with an average total treatment time of 1 month for complete healing of the defect.

Conclusion

The current results suggest that the technique of elastic ligature is a desirable solution for pilonidal sinus, because of the initial low costs, no need for hospitalization, and good patient tolerance.
Dose–response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial
Authors: Blüher Matthias , Rosenstock Julio , Hoefler Josef , Manuel Raymond , Hennige Anita M.
Published: December 2023

Aims/hypothesis

The aim of this study was to assess the dose–response effects of the subcutaneous glucagon receptor/glucagon-like peptide-1 receptor dual agonist survodutide (BI 456906) on HbA1c levels and bodyweight reduction.

Methods

This Phase II, multicentre, randomised, double-blind, parallel-group, placebo-controlled study, conducted in clinical research centres, assessed survodutide in participants aged 18–75 years with type 2 diabetes, an HbA1c level of 53–86 mmol/mol (7.0–10.0%) and a BMI of 25–50 kg/m2 on a background of metformin therapy. Participants were randomised via interactive response technology to receive survodutide (up to 0.3, 0.9, 1.8 or 2.7 mg once weekly [qw; dose group (DG) 1–4, respectively] or 1.2 or 1.8 mg twice weekly [DG 5 and 6, respectively]), placebo or semaglutide (up to 1.0 mg qw). Participants and all those involved in the trial conduct/analysis were blinded; the semaglutide arm was open-label. The primary endpoint was absolute change from baseline in HbA1c after 16 weeks’ treatment. The key secondary endpoint was relative change from baseline in bodyweight after 16 weeks’ treatment.

Results

A total of 413 participants were randomised (DG1, n=50; DG2, n=50; DG3, n=52; DG4, n=50; DG5, n=51; DG6, n=50; semaglutide, n=50; placebo, n=60). The full analysis set comprised 411 treated participants (DG6, n=49; placebo, n=59). Adjusted mean (95% CI) HbA1c decreased from baseline (mean ± SD 64.7±9.2 mmol/mol [8.07±0.84%] after 16 weeks’ treatment: DG1 (n=41), −9.92 mmol/mol (−12.27, −7.56; −0.91% [−1.12, −0.69]); DG2 (n=46), −15.95 mmol/mol (−18.27, −13.63; −1.46% [−1.67, −1.25]); DG3 (n=36), −18.72 mmol/mol (−21.15, −16.29; −1.71% [−1.94, −1.49]); DG4 (n=33), −17.01 mmol/mol (−19.59, −14.43; −1.56% [−1.79, −1.32]); DG5 (n=44), −17.84 mmol/mol (−20.18, −15.51; −1.63% [−1.85, −1.42]); DG6 (n=36), −18.38 mmol/mol (−20.90, −15.87; −1.68% [−1.91, −1.45]). The mean reduction in HbA1c was similar with low-dose survodutide (DG2: −15.95 mmol/mol [−1.46%]; n=46) and semaglutide (−16.07 mmol/mol [−1.47%]; n=45). Mean (95% CI) bodyweight decreased dose-dependently up to −8.7% (−10.1, −7.3; DG6, n=37); survodutide ≥1.8 mg qw produced greater bodyweight reductions than semaglutide (−5.3% [−6.6, −4.1]; n=45). Adverse events (AEs) were reported for 77.8% of survodutide-treated participants (mainly gastrointestinal), 52.5% receiving placebo and 52.0% receiving semaglutide.

Conclusions/interpretation

Survodutide reduced HbA1c levels and bodyweight after 16 weeks’ treatment in participants with type 2 diabetes. Dose-related gastrointestinal AEs could be mitigated with slower dose escalations.

Trial registration

ClinicalTrials.gov NCT04153929 and EudraCT 2019-002390-60.

Funding

Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.

Graphical Abstract
Hyperglycaemia, diabetes and risk of fragility fractures: observational and Mendelian randomisation studies
Authors: Emanuelsson Frida , Afzal Shoaib , Jørgensen Niklas R. , Nordestgaard Børge G. , Benn Marianne
Published: December 2023

Aims/hypothesis

Fragility fractures may be a complication of diabetes, partly caused by chronic hyperglycaemia. We hypothesised that: (1) individuals with hyperglycaemia and diabetes have increased risk of fragility fracture; (2) hyperglycaemia is causally associated with increased risk of fragility fracture; and (3) diabetes and fragility fracture jointly associate with the highest risk of all-cause mortality.

Methods

In total, 117,054 individuals from the Copenhagen City Heart Study and the Copenhagen General Population Study (the Copenhagen studies) and 390,374 individuals from UK Biobank were included for observational and one-sample Mendelian randomisation (MR) analyses. Fragility fractures were defined as fractures at the hip, spine and arm (humerus/wrist), collected from national health registries. Summary data for fasting glucose and HbA1c concentrations from 196,743 individuals in the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) were combined with data on fragility fractures from the Copenhagen studies in two-sample MR analyses.

Results

Higher fasting and non-fasting glucose and HbA1c concentrations were associated with higher risk of any fragility fracture (p<0.001). Individuals with vs without diabetes had HRs for fragility fracture of 1.50 (95% CI 1.19, 1.88) in type 1 diabetes and 1.22 (1.13, 1.32) in type 2 diabetes. One-sample MR supported a causal association between high non-fasting glucose concentrations and increased risk of arm fracture in the Copenhagen studies and UK Biobank combined (RR 1.41 [1.11, 1.79], p=0.004), with similar results for fasting glucose and HbA1c in two-sample MR analyses (ORs 1.50 [1.03, 2.18], p=0.03; and 2.79 [1.12, 6.93], p=0.03, respectively). The corresponding MR estimates for any fragility fracture were 1.18 (1.00, 1.41), p=0.06; 1.36 (0.89, 2.09), p=0.15; and 2.47 (0.95, 6.43), p=0.06, respectively. At age 80 years, cumulative death was 27% in individuals with fragility fracture only, 54% in those with diabetes only, 67% in individuals with both conditions and 17% in those with neither.

Conclusions/interpretation

Hyperglycaemia and diabetes are risk factors for fragility fracture and one- and two-sample MR analyses supported a causal effect of hyperglycaemia on arm fractures. Diabetes and previous fragility fracture jointly conferred the highest risk of death in the general population.

Graphical Abstract
Improvement of electrical and mechanical properties of laser welded lap joints via dimensional optimization
Authors: Horváth Gábor , Körmöczi Andor , Szörényi Tamás , Geretovszky Zsolt
Published: December 2023

With the proliferation of electric drivetrains, the development and optimization of joining techniques for the fabrication of battery packs became a prime manufacturing topic. Decreasing the electrical resistance and increasing the mechanical strength of the welds at the individual cell level are of great importance not only for productivity and efficiency but also for safety and sustainability purposes. Lasers offer an advanced, highly automatable solution for battery cell joining. Usually, the optimization focuses on the laser parameters or the scanning speed. However, the most widespread battery welding geometry, the so-called lap geometry, allows alternative possibilities for joint property optimization. The novelty of our approach is that we focus on systematic experimental investigation of the effects of dimensional parameters and the layout of the weld pattern. Systematic experiments reveal that the shape and size of the weld area have substantial effect on the properties of the laser welded joint. Our results prove that a rather substantial gain can be achieved in both the electrical and mechanical properties when the weld consists of at least two parallel bead segments. We also show that it is beneficial by both means if the segments have the greatest individual length and placed apart at the maximum feasible distance. The orientation of the straight segments affects the mechanical and electrical behavior differently: strongest welds consist of weld segments oriented in parallel, while the smallest resistance can be achieved using segments oriented perpendicular to the direction of current flow, respectively.
Culturomics reveals a hidden world of vaginal microbiota with the isolation of 206 bacteria from a single vaginal sample
Authors: Abou Chacra Linda , Benatmane Amel , Iwaza Rim , Ly Claudia , Alibar Stéphane , Armstrong Nicholas , Mediannikov Oleg , Bretelle Florence , Fenollar Florence
Published: December 2023

The composition of the vaginal microbiota is known to be influenced by various factors and to be associated with several disorders affecting women’s health. Although metagenomics is currently a widely used method for studying the human microbiota, it has certain limitations, such as a lack of information on bacterial viability. It is therefore important to use culture-based methods such as culturomics. Here, we used 35 different culture conditions to comprehensively characterize the vaginal bacterial diversity of a single woman's flora. A total of 206 bacterial species, belonging to six phyla (for a little more than half to Firmicutes, followed mainly by Actinobacteria, Bacteroidetes, and Proteobacteria) and 45 families, and 2 fungal species were cultivated. While several species of lactobacilli have been isolated, a wide variety of other bacteria were also separated, including 65 never reported before in vaginal flora, including a new bacterial species, Porphyromonas vaginalis sp. nov. Extensive culture-based methods are essential to establish a comprehensive, evidence-based repertoire of bacterial viability. If combined with molecular methods, they can provide a much more thorough understanding of the vaginal microbiota and fulfil the unknown part of metagenomic studies.
The crown-of-thorns seastar species complex: knowledge on the biology and ecology of five corallivorous Acanthaster species
Authors: Uthicke Sven , Pratchett Morgan S. , Bronstein Omri , Alvarado Juan José , Wörheide Gert
Published: December 2023

Coral-eating crown-of-thorns seastars (CoTS, Acanthaster spp.) are major contributors to the coral reef crises across the Indo-Pacific region. Until recently, CoTS throughout the Indo-Pacific were regarded to be a single species, Acanthaster planci. However, genetic and morphological analyses demonstrated that there are at least four distinct species: Acanthaster benziei in the Red Sea, Acanthaster mauritiensis and A. planci in the Indian Ocean, and Acanthaster cf. solaris in the western Pacific. Acanthaster cf. ellisii in the eastern Pacific needs more taxonomic attention. Here, we review the biological knowledge for each species adapting a pragmatic geographical species definition and using a systematic literature review complemented with more focused searches for individual species. The vast majority of CoTS research (88%) was conducted on A. cf. solaris, with much of this research undertaken on the Great Barrier Reef or in Japan. Many studies of A. cf. solaris are focused on monitoring or documenting incidences of outbreaks, though there is a solid base of knowledge on larval, juvenile and adult ecology derived from field and laboratory experiments. By contrast, most of the published studies on the four remaining species simply document cases of population outbreaks. The major taxonomic bias in CoTS research constitutes a significant limitation for understanding and managing these species for two reasons. First, even for A. cf. solaris, which is the most studied species, limited fundamental knowledge of their biology and ecology constrains understanding of the drivers of outbreaks and hinders corresponding management actions for prevention and control of these events. Second, understanding and management of other species are predicated on the assumption that all CoTS species have similar biology and behaviour, an unsatisfying assumption for ecosystem management.
Enhanced Fat Graft Viability and Remodeling Using a Helium-based Radiofrequency Device to Prepare the Recipient Site
Authors: Ruff Paul G. , Sterodimas Aris
Published: December 2023

Background

Improvements to autologous fat grafting for soft tissue augmentation are needed to overcome the unpredictable volume retention. Approaches such as fat harvesting and processing, injection technique, preparation of the recipient site, and supplemental biologics are topics of ongoing research. Here, an energy-based device was investigated as a stimulatory tool for recipient site preparation for improving fat graft retention.

Objective

The objective was to measure the stimulatory responses in fat grafts after 4 weeks when using a helium-based radiofrequency device to pretreat the recipient tissue.

Methods

Using an autologous fat grafting mouse model, the inguinal fat pad was grafted in a small cranial pocket after either a saline injection alone (control) or a saline injection followed by pretreatment (treated). The fat pad was resected after 4 weeks, sectioned and stained with immunofluorescence markers to investigate tissue remodeling.

Results

Pretreatment resulted in higher viability of adipocytes, a higher concentration of viable ASCs in areas of adipose tissue regeneration, and localized macrophages in the areas of regeneration when compared to the control. There was no observable difference in vascularity or angiogenesis. The staining for ASCs was higher in the pretreated group in comparison with the control group (5.0% vs. 3.3%, p=0.36) when using a pixel classifier in QuPath in the viable adipose tissue regions.

Conclusions

The use of a helium-based radiofrequency device as a pretreatment tool appears to increase the viability of the adipose tissue likely due to higher concentration of ASCs. The apparent increase in viable ASCs may be due to enhanced proliferation or paracrine recruitment of these cells in response to the helium-based radiofrequency treatment.

No Level Assigned

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Bullet List of Important Points:

Pretreatment of the fat graft recipient site increases the viability of the adipose tissue after 4 weeks in comparison with the control grafts.

The increased viability is likely due to the observed increase in adipose-derived stem cells in the pretreated group.

Pretreatment enhanced the adipose tissue remodeling as colocalization of adipose-derived stem cells and macrophages showed an active remodeling, whereas the control group exhibited more necrotic and fibrotic tissue.
Effectiveness of tixagevimab/cilgavimab in patients with hematological malignancies as a pre-exposure prophylaxis to prevent severe COVID-19: a Czech retrospective multicenter study
Authors: Demel Ivo , Skopal David , Šafránková Eliška , Rozsívalová Petra , Jindra Pavel , Šrámek Jiří , Turková Adéla , Vydra Jan , Labská Klára , Vedrová Jana , Čerňan Martin , Szotkowski Tomáš , Móciková Heidi , Hynková Lenka , Šušol Ondrej , Kováčová Ingrid , Belada David , Hájek Roman
Published: December 2023

Despite lower virulence, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) still poses a relevant threat for immunocompromised patients. A retrospective multicentric study was conducted to evaluate the efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) with a 6-month follow-up for preventing severe COVID-19 in adult patients with hematology malignancy. Among the 606 patients in the cohort, 96 (16%) contracted COVID-19 with a median of 98.5 days after Evusheld administration. A total of 75% of patients had asymptomatic or mild severity of COVID-19, while just 25% of patients with SARS-CoV-2 positivity had to be hospitalized. Two patients (2%) died directly, and one patient (1%) in association with COVID-19. Eight patients (1.3%) of every cohort experienced adverse events related to Evusheld, mostly grade 1 and of reversible character. It was found that complete vaccination status or positive seroconversion was not associated with lower risk of COVID-19 infection. Previous treatment with an anti-CD20 monoclonal antibody was associated with higher rates of COVID-19, while previous treatment with anti-CD38 monoclonal antibody was not, as was the case for recipients of hematopoietic stem cell transplantation or CAR-T cell therapy. Presence of other comorbidities was not associated with more severe COVID-19. The results support the growing evidence for Evusheld’s efficacy against severe COVID-19 in patients with hematology malignancies.
Safe use of contrast media in myasthenia gravis: systematic review and updated European Society of Urogenital Radiology Contrast Media Safety Committee guidelines
Authors: Geenen Remy W. F. , Roditi Giles , Bellin Marie-France , Bertolotto Michele , Brismar Torkel , Correas Jean-Michel , Dekkers Ilona A. , Heinz-Peer Gertraud , Mahnken Andreas H. , van der Molen Aart J. , Quattrocchi Carlo C. , Radbuch Alexander , Reimer Peter , Sebastià Maria , Stacul Fulvio , Romanini Laura , Clément Olivier ,   on behalf of the Contrast Media Safety Committee
Published: December 2023

Objectives

It is uncertain whether modern iodine-based or gadolinium-based contrast media (CM) administration can lead to increased symptoms in patients with myasthenia gravis.

Methods

A systematic search in Medline was conducted for studies describing the symptomatology of myasthenia gravis patients before and after receiving intravenous (IV) CM and having a matched control group of myasthenia gravis patients who did not receive IV CM.

Results

Three retrospective studies were selected with a total of 374 myasthenia gravis patients who received iodine-based CM and a total of 313 myasthenia gravis patients who underwent unenhanced CT and served as controls. Pooling of the data from the three retrospective studies showed that in 23 of 374 patients, increased symptoms after iodine-based CM administration were described (6.1%). Increased symptomatology also occurred in 11 of 313 patients after unenhanced CT (3.5%). When looking more deeply into the data of the three studies, conflicting results were found, as two articles did not find any relationship between CM and myasthenia gravis symptoms. The remaining study only found a significant increase in symptomatology within 1 day after CT scanning: seven patients (6.3%) in the contrast-enhanced CT group and one patient (0.6%) in the unenhanced CT group (p = 0.01).

Conclusions

There is limited evidence on the relationship between CM and myasthenia gravis symptoms. In the vast majority of myasthenia gravis patients, CM are safe. Probably, in less than 5% of the patients, iodine-based CM administration may lead to increased severity of the symptoms within the first 24 h after administration.

Clinical relevance statement

Be aware that intravenous administration of iodine-based contrast media can lead to an increase of symptoms in patients with myasthenia gravis within the first 24 h. This can probably happen in less than 5% of the patients.

Key Points

• It is unclear whether modern contrast media can lead to increased symptoms in myasthenia gravis patients after intravenous administration.

• There seems to be a small risk of increased myasthenia gravis symptoms within 24 h after intravenous administration of iodine-based contrast media, probably in less than 5% of the administrations.

• Gadolinium-based contrast media are safe for patients with myasthenia gravis.
LD block disorder-specific pleiotropic roles of novel CRHR1 in type 2 diabetes and depression disorder comorbidity
Authors: del Bosque-Plata Laura , Amin Mutaz , González-Ramírez Ricardo , Wu Rongling , Postolache Teodor T. , Vergare Michael , Gordon Derek , Gragnoli Claudia
Published: December 2023

Major depressive disorder (MDD) and type 2 diabetes (T2D) are complex disorders whose comorbidity can be due to hypercortisolism and may be explained by dysfunction of the corticotropin-releasing hormone receptor 1 (CRHR1) and cortisol feedback within the hypothalamic–pituitary–adrenal axis (HPA axis). To investigate the role of the CRHR1 gene in familial T2D, MDD, and MDD-T2D comorbidity, we tested 152 CRHR1 single-nucleotide-polymorphisms (SNPs), via 2-point parametric linkage and linkage disequilibrium (LD; i.e., association) analyses using 4 models, in 212 peninsular families with T2D and MDD. We detected linkage/LD/association to/with MDD and T2D with 122 (116 novel) SNPs. MDD and T2D had 4 and 3 disorder-specific novel risk LD blocks, respectively, whose risk variants reciprocally confirm one another. Comorbidity was conferred by 3 novel independent SNPs. In silico analyses reported novel functional changes, including the binding site of glucocorticoid receptor-alpha [GR-α] on CRHR1 for transcription regulation. This is the first report of CRHR1 pleiotropic linkage/LD/association with peninsular familial MDD and T2D. CRHR1 contribution to MDD is stronger than to T2D and may antecede T2D onset. Our findings suggest a new molecular-based clinical entity of MDD-T2D and should be replicated in other ethnic groups.
Increasing age of multiple sclerosis onset from 1920 to 2022: a population-based study
Authors: Habbestad A. , Willumsen J. S. , Aarseth J. H. , Grytten N. , Midgard R. , Wergeland S. , Myhr K. M. , Torkildsen Ø.
Published: December 2023

Objective

To study the age at onset of relapsing–remitting multiple sclerosis (RRMS) during the past century.

Methods

This is a population-based cohort study of persons diagnosed with RRMS in Hordaland, Møre, and Romsdal counties, Western Norway, from 1920 to 2022. Individual patient data were available and assessed from previously conducted prevalence and incidence studies in addition to hospital records up until October 31, 2022. Participants were categorized according to onset period and analyzed for temporal trends in age at onset, time from onset to diagnosis, and distribution of onset over time.

Results

We identified 3364 persons with confirmed RRMS. The mean age at onset significantly increased (p < 0.001) throughout the study period, despite a decrease in time from symptom onset to diagnosis (p < 0.001). The proportion of persons with MS onset after 50 years of age increased from 2.6% before 1970 to 11.9% after 2010. We also found a trend toward a bimodal distribution of age at onset that peaked at around 30 years and 40–45 years of age in the latest period.

Conclusion

Age at onset of MS significantly increased throughout the study period. This was mainly due to an increasing number of persons with MS, predominantly female, experiencing onset after 40–45 years of age. This bimodal distribution could indicate different susceptibility periods of MS or changes in exposure to risk factors during the observation period.
In silico optical modulation of spiral wave trajectories in cardiac tissue
Authors: Hussaini Sayedeh , Majumder Rupamanjari , Krinski Valentin , Luther Stefan
Published: December 2023

Life-threatening cardiac arrhythmias such as ventricular tachycardia and fibrillation are common precursors to sudden cardiac death. They are associated with the occurrence of abnormal electrical spiral waves in the heart that rotate at a high frequency. In severe cases, arrhythmias are combated with a clinical method called defibrillation, which involves administering a single global high-voltage shock to the heart to reset all its activity and restore sinus rhythm. Despite its high efficiency in controlling arrhythmias, defibrillation is associated with several negative side effects that render the method suboptimal. The best approach to optimize this therapeutic technique is to deepen our understanding of the dynamics of spiral waves. Here, we use computational cardiac optogenetics to study and control the dynamics of a single spiral wave in a two-dimensional, electrophysiologically detailed, light-sensitive model of a mouse ventricle. First, we illuminate the domain globally by applying a sequence of periodic optical pulses with different frequencies in the sub-threshold regime where no excitation wave is induced. In doing so, we obtain epicycloidal, hypocycloidal, and resonant drift trajectories of the spiral wave core. Then, to effectively control the wave dynamics, we use a method called resonant feedback pacing. In this approach, each global optical pulse is applied when the measuring electrode positioned on the domain registers a predefined value of the membrane voltage. This enables us to steer the spiral wave in a desired direction determined by the position of the electrode. Our study thus provides valuable mechanistic insights into the success or failure of global optical stimulation in executing efficient arrhythmia control.