bluuebunny/crossref_metadata_2025 huggingface dataset:
Practical considerations for the use of fenfluramine to manage patients with Dravet syndrome or Lennox–Gastaut syndrome in clinical practice
Authors: Wirrell Elaine C. , Lagae Lieven , Scheffer Ingrid E. , Cross J. Helen , Specchio Nicola , Strzelczyk Adam
Published: July 2024

Fenfluramine (FFA), an antiseizure medication (ASM) with serotonergic and sigma‐1 receptor activity, is used to manage patients with developmental and epileptic encephalopathies (DEEs). It is approved in the US for treating seizures associated with Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS) in patients ≥2 years old and as add‐on therapy for seizures associated with DS and LGS in the EU, UK, and Japan in similarly aged patients. Consensus guidelines for treatment of DS have recommended FFA to be an early‐line ASM, and it has also shown efficacy in managing seizures associated with LGS. DS and LGS are DEEs associated with a range of seizure types, developmental impairments, and multiple comorbidities. Here we provide case vignettes describing 4 patients (3 DS and 1 LGS) aged 4–29 years old in whom up to 14 ASMs had previously failed, to illustrate real‐world practice issues encountered by neurologists. This review provides guidance on the use of FFA in the context of ASM polytherapy and drug–drug interactions (DDIs), behavioral issues, dose titration, and adverse events. Along with data from the clinical trial program, these case vignettes emphasize the low risk of DDIs, a generally well‐tolerated safety profile, and other seizure and nonseizure benefits (eg, improved cognition and sleep) associated with the use of FFA in DS or LGS.

Plain Language Summary

Fenfluramine is used to treat seizures in individuals with Dravet syndrome and Lennox–Gastaut syndrome, but there are a range of issues that clinicians may face when treating patients. This review highlights four patients from the authors’ everyday clinical work and offers guidance and practical considerations by neurologists with expertise in managing these complex conditions related to drug interactions, dosing, and side effects associated with fenfluramine.
Experimental study on the fracture surface morphological characteristics and permeability characteristics of sandstones with different particle sizes
Authors: Zhengzheng Cao , Xiangqian Yang , Peiding Zhang , Zhenhua Li , Feng Du , Wenqiang Wang , Huanqi Chen
Published: July 2024

To study the seepage law and sectional morphological characteristics in splitting sandstones of different grain sizes, three‐dimensional morphological scanning tests and seepage characteristics tests are conducted on the splitting rock samples of siltstone, fine‐, medium‐ and coarse‐grained sandstone, and the differences in morphological characteristics and seepage law in different grain size sandstones are compared and analyzed. The test results show that the sections of siltstone and fine‐grained sandstone have the overall morphological characteristics of “one high and one low” with large undulation, while the sections of medium‐ and coarse‐grained sandstone have a more uniform distribution and less undulation. In the relationship between pressure gradient and flow velocity, siltstone and fine‐grained sandstone are precisely characterized by the Forchheimer formula, and medium‐ and coarse‐grained sandstone are well characterized by the Izbash formula, and the fitting effect is good. The results of the study are of great reference significance for improving the cross‐sectional morphological characteristics and seepage law of the splitting rock samples.
Examining effects of a novel estrogenic perfluoro-alcohol, 1H,1H,8H,8H-Perfluorooctane-1,8-diol (FC8-diol), using the fathead minnow EcoToxChip
Authors: Santana Rodriguez Kelvin J , Villeneuve Daniel L , Cavallin Jenna E , Blackwell Brett R , Hoang John , Hofer Rachel N , Jensen Kathleen M , Kahl Michael D , Kutsi Robin N , Stacy Emma , Morshead Mackenzie L , Ankley Gerald T
Published: July 2024

In a previous in vivo study, adult male fathead minnows (Pimephales promelas) were exposed via water for 4 days to 1H,1H,8H,8H-perfluorooctane-1,8-diol (FC8-diol). The present study expands on the evaluation of molecular responses to this perfluoro-alcohol by analyzing 26 male fathead minnow liver RNA samples from that study (five from each test concentration: 0, 0.018, 0.051, 0.171, and 0.463 mg FC8-diol/L) using fathead minnow EcoToxChips Ver. 1.0. EcoToxChips are a quantitative polymerase chain reaction array that allows for simultaneous measurement of >375 species-specific genes of toxicological interest. Data were analyzed with the online tool EcoToxXplorer. Among the genes analyzed, 62 and 96 were significantly up- and downregulated, respectively, by one or more FC8-diol treatments. Gene expression results from the previous study were validated, showing an upregulation of vitellogenin mRNA (vtg) and downregulation of insulin-like growth factor 1 mRNA (igf1). Additional genes related to estrogen receptor activation including esr2a (estrogen receptor 2a) and esrrb (estrogen related receptor beta) were also affected, providing further confirmation of the estrogenic nature of FC8-diol. Furthermore, genes involved in biological pathways related to lipid and carbohydrate metabolism, innate immune response, endocrine reproduction, and endocrine thyroid were significantly affected. These results both add confidence in the use of the EcoToxChip tool for inferring chemical mode(s) of action and provide further insights into the possible biological effects of FC8-diol.
Principles, fabrication, and applications of halide perovskites‐based memristors
Authors: Cheng Xiaozhe , Dou Zhitao , Lian Hong , Qin Zhitao , Guo Hongen , Li Xifeng , Wong Wai‐Yeung , Dong Qingchen
Published: July 2024

In recent decades, the microelectronics industry has developed rapidly based on the von Neumann architecture and under the guidance of Moore's law. However, as the size of electronic devices approaches the limit and power consumption increases, traditional microelectronic materials and devices are facing more and more challenges. As a new type of semiconductor material, halide perovskites (HPs) have excellent photoelectric characteristics, such as high carrier mobility, controllable band structure, etc., which have been widely used in solar cells, light emitting diodes (LEDs), photodetectors, memristors, and in other fields. Among them, the memristor, as a new type of electronic device, is very promising for in‐memory computing with low power consumption by breaking the limit of von Neumann architecture. Especially, HPs‐based memristors show outstanding photoelectric response performance, low power consumption, and flexible wearability, allowing them to hold great application potential in logical operation, polymorphic storage, and neuromorphic computing, etc. In this review, we first briefly introduce the basic characteristics and preparation methods of HPs. Secondly, the development history, device structure, and performance parameters of memristors are depicted in detail. Thirdly, the resistance mechanism and application of HPs‐based memristors are discussed. Finally, the research status and development prospects of HPs‐based memristors are outlined.
Emerging nanomedicine strategies for hepatocellular carcinoma therapy
Authors: Guo Chen , Zhang Jiayu , Cai Xiaomeng , Dou Rui , Tang Jiaruo , Huang Zhengyuan , Wang Xueting , Guo Yan , Chen Hanqing , Chen Jun
Published: July 2024

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with a range of risk factors, including viral infections, alcoholic liver disease, exposure to fungal toxins, obesity, and type 2 diabetes. Despite advancements in early detection and treatment, HCC continues to exhibit a high rate of recurrence. Patients in advanced stages have a poor prognosis, and the survival rate after cancer metastasis is notably low. Consequently, there exists an urgent necessity for novel treatment strategies. Nanomedicine possesses superior attributes, such as targeted administration and responsive drug release within the tumor microenvironment. These systems demonstrate potential in HCC treatment by facilitating the transportation of diverse therapeutic drugs. This comprehensive review aims to delve into the application of nanoparticle drug delivery systems in the management of liver tumors, with particular emphasis on formulation, targeted strategies specific to liver tumors, and various methods of drug release. By offering insights into the utilization of nanoparticle drug delivery systems in the realm of liver tumor treatment, this review endeavors to assist readers in exploring their vast potential.
Cell‐type‐specific expression analysis of liver transcriptomics with clinical parameters to decipher the cause of intrahepatic inflammation in chronic hepatitis B
Authors: Wang Jun , Li Qian , Qiu Yuanwang , Kitanovski Simo , Wang Chen , Zhang Chenxia , Li Fahong , Li Xiaoguang , Zhang Zhenfeng , Huang Lihua , Zhang Jiming , Hoffmann Daniel , Lu Mengji , Lu Hongzhou
Published: July 2024

Functional cure for chronic hepatitis B (CHB) remains challenging due to the lack of direct intervention methods for hepatic inflammation. Multi‐omics research offers a promising approach to understand hepatic inflammation mechanisms in CHB. A Bayesian linear model linked gene expression with clinical parameters, and population‐specific expression analysis (PSEA) refined bulk gene expression into specific cell types across different clinical phases. These models were integrated into our analysis of key factors like inflammatory cells, immune activation, T cell exhaustion, chemokines, receptors, and interferon‐stimulated genes (ISGs). Validation through multi‐immune staining in liver specimens from CHB patients bolstered our findings. In CHB patients, increased gene expression related to immune cell activation and migration was noted. Marker genes of macrophages, T cells, immune‐negative regulators, chemokines, and ISGs showed a positive correlation with serum alanine aminotransferase (ALT) levels but not hepatitis B virus DNA levels. The PSEA model confirmed T cells as the source of exhausted regulators, while macrophages primarily contributed to chemokine expression. Upregulated ISGs (ISG20, IFI16, TAP2, GBP1, PSMB9) in the hepatitis phase were associated with T cell and macrophage infiltration and positively correlated with ALT levels. Conversely, another set of ISGs (IFI44, ISG15, IFI44L, IFI6, MX1) mainly expressed by hepatocytes and B cells showed no correlation with ALT levels. Our study presents a multi‐omics analysis integrating bulk transcriptomic, single‐cell sequencing data, and clinical data from CHB patients to decipher the cause of intrahepatic inflammation in CHB. The findings confirm that macrophages secrete chemokines like CCL20, recruiting exhausted T cells into liver tissue; concurrently, hepatocyte innate immunity is suppressed, hindering the antiviral effects of ISGs.
Comparative proteomics uncovers low asparagine content in Plasmodium tRip‐KO proteins
Authors: Pitolli Martina , Cela Marta , Kapps Delphine , Chicher Johana , Despons Laurence , Frugier Magali
Published: July 2024

tRNAs are not only essential for decoding the genetic code, but their abundance also has a strong impact on the rate of protein production, folding, and on the stability of the translated messenger RNAs. Plasmodium expresses a unique surface protein called tRip, involved in the import of exogenous tRNAs into the parasite. Comparative proteomic analysis of the blood stage of wild‐type and tRip‐KO variant of P. berghei parasites revealed that downregulated proteins in the mutant parasite are distinguished by a bias in their asparagine content. Furthermore, the demonstration of the possibility of charging host tRNAs with Plasmodium aminoacyl‐tRNA synthetases led us to propose that imported host tRNAs participate in parasite protein synthesis. These results also suggest a novel mechanism of translational control in which import of host tRNAs emerge as regulators of gene expression in the Plasmodium developmental cycle and pathogenesis, by enabling the synthesis of asparagine‐rich regulatory proteins that efficiently and selectively control the parasite infectivity.
Unpaired fundus image enhancement based on constrained generative adversarial networks
Authors: Yang Luyao , Yao Shenglan , Chen Pengyu , Shen Mei , Fu Suzhong , Xing Jiwei , Xue Yuxin , Chen Xin , Wen Xiaofei , Zhao Yang , Li Wei , Ma Heng , Li Shiying , Tuchin Valery V. , Zhao Qingliang
Published: July 2024

Fundus photography (FP) is a crucial technique for diagnosing the progression of ocular and systemic diseases in clinical studies, with wide applications in early clinical screening and diagnosis. However, due to the nonuniform illumination and imbalanced intensity caused by various reasons, the quality of fundus images is often severely weakened, brings challenges for automated screening, analysis, and diagnosis of diseases. To resolve this problem, we developed strongly constrained generative adversarial networks (SCGAN). The results demonstrate that the quality of various datasets were more significantly enhanced based on SCGAN, simultaneously more effectively retaining tissue and vascular information under various experimental conditions. Furthermore, the clinical effectiveness and robustness of this model were validated by showing its improved ability in vascular segmentation as well as disease diagnosis. Our study provides a new comprehensive approach for FP and also possesses the potential capacity to advance artificial intelligence‐assisted ophthalmic examination.
T cells and macrophages jointly modulate osteogenesis of mesenchymal stromal cells
Authors: Murayama Masatoshi , Shinohara Issei , Toya Masakazu , Susuki Yosuke , Lee Max L. , Young Bill , Gao Qi , Chow Simon Kwoon‐Ho , Goodman Stuart B.
Published: July 2024

Approximately 5%–10% of fractures go on to delayed healing and nonunion, posing significant clinical, economic, and social challenges. Current treatment methods involving open bone harvesting and grafting are associated with considerable pain and potential morbidity at the donor site. Hence, there is growing interest in minimally invasive approaches such as bone marrow aspirate concentrate (BMAC), which contains mesenchymal stromal cells (MSCs), macrophages (Mφ), and T cells. However, the use of cultured or activated cells for treatment is not yet FDA‐approved in the United States, necessitating further exploration of optimal cell types and proportions for effective bone formation. As our understanding of osteoimmunology advances, it has become apparent that factors from anti‐inflammatory Mφ (M2) promote bone formation by MSCs. Additionally, M2 Mφ promote T helper 2 (Th2) cells and Treg cells, both of which enhance bone formation. In this study, we investigated the interactions among MSCs, Mφ, and T cells in bone formation and explored the potential of subsets of BMAC. Coculture experiments were conducted using primary MSCs, Mφ, and CD4+ T cells at specific ratios. Our results indicate that nonactivated T cells had no direct influence on osteogenesis by MSCs, while coculturing MSCs with Mφ and T cells at a ratio of 1:5:10 positively impacted bone formation. Furthermore, higher numbers of T cells led to increased M2 polarization and a higher proportion of Th2 cells in the early stages of coculture. These findings suggest the potential for enhancing bone formation by adjusting immune and mesenchymal cell ratios in BMAC. By understanding the interactions and effects of immune cells on bone formation, we can develop more effective strategies and protocols for treating bone defects and nonunions. Further studies are needed to investigate these interactions in vivo and explore additional factors influencing MSC‐based therapies.
Silencing UBE2K inhibits the growth of glioma cells by inducing the autophagy‐related apoptosis
Authors: Xin Zhen , Holgersson Kristian , Zhu Pengcheng , Tan Hongtu , Shi Guangyan , Szekely Laszlo , Wu Tao
Published: July 2024

Glioma is a central nervous system (CNS) malignant tumor with high heterogeneity and mortality, which severely threatens the health of patients. The overall survival of glioma patients is relatively short and it is critical to identify new molecular targets for developing effective treatment strategies. UBE2K is a ubiquitin conjugating enzyme with oncogenic function in several malignant tumors. However, whether UBE2K participates in gliomas remains unknown. Herein, in glioma cells, UBE2K was found highly expressed in U87 and U251 cells. Subsequently, U87 and U251 cells were transfected with si‐UBE2K to silence UBE2K, with the si‐NC transfection as the negative control. In both U87 and U251 cells, the cell viability was sharply reduced by transfecting si‐UBE2K for 48 and 72 h. Markedly decreased colony number, reduced number of migrated cells and invaded cells, and declined relative wound healing rate were observed in si‐UBE2K transfected U87 and U251 cells. Moreover, the Bcl‐2 level was markedly reduced, while the Bax and cleaved‐caspase‐3 levels were sharply increased in U87 and U251 cells after the si‐UBE2K transfection. Furthermore, the p62 level was signally declined, while the Beclin‐1 and LC‐3 II/I levels were greatly increased in U87 and U251 cells by the si‐UBE2K transfection. Furthermore, the facilitating effect of si‐UBE2K on the apoptosis and autophagy in U87 and U251 cells was abolished by the coculture of 3‐MA, an inhibitor of autophagy. Collectively, UBE2K facilitated the in vitro growth of glioma cells, possibly by inhibiting the autophagy‐related apoptosis, which might be a promising target for treating glioma.
Effects of substituted chalcogen atoms on excited state proton transfer reaction for 2,5‐bis(benzoxazole‐2‐yl)‐thiophene‐3,4‐diol derivatives: A theoretical study
Authors: Chen Jiahe , Zhao Jinfeng
Published: July 2024

Motivated by the captivating allure of exquisitely regulated characteristics exhibited by 2‐(2‐hydroxyphenyl)‐benzoxazole and its derivatives in the domains of photochemistry and photophysics, our current endeavor primarily focuses on delving into the intricacies of photo‐induced excited state reactions for derivatives of 2,5‐bis(benzoxazol‐2‐yl)‐thiophene‐3,4‐diol (BTD). Given the profound impact of chalcogen element doping, our primary focus lies in investigating the excited state behaviors of BTD‐O, BTD‐S, and BTD‐Se fluorophores. Through simulations encompassing variations in geometry and vertical excitation charge reorganization, we unveil atomic‐electronegativity‐dependent hydrogen bonding interactions and photoexcitation‐induced charge recombination that can significantly augment the intramolecular double proton transfer (ESDPT) reaction in the excited state for BTD‐O, BTD‐S, and BTD‐Se fluorophores. By constructing potential energy surfaces and identifying transition state forms, we elucidate the ultrafast stepwise ESDPT mechanism facilitated by the low potential barriers. Moreover, we rigorously validate the chalcogen atomic electronegativity‐driven regulation of the stepwise ESDPT mechanism. We sincerely anticipate that manipulating solvent polarity will pave the way for groundbreaking advancements in luminescent materials.
Clinical outcomes in patients switching from agalsidase beta to migalastat: A Fabry Registry analysis
Authors: Pisani Antonio , Wilson Kathryn M. , Batista Julie L. , Kantola Ilkka , Ortiz Alberto , Politei Juan , Al‐Shaar Laila , Maski Manish , Crespo Ana , Ponce Elvira , Linhart Aleš
Published: July 2024

Fabry Registry data were analyzed among 83 agalsidase beta‐treated patients with Fabry disease who switched to migalastat. Outcomes (estimated glomerular filtration rate [eGFR], urine protein‐creatinine ratio [UPCR], plasma globotriaosylceramide [GL‐3], plasma globotriaosylsphingosine [lyso‐GL‐3], interventricular septal wall thickness [IVST], left posterior wall thickness [LPWT], left ventricular mass index [LVMI]) were assessed using linear mixed models to estimate annual change over time in the pre‐ and postswitch periods. eGFR decreased throughout both periods (preswitch: −0.85 mL/min/1.73 m2/year; postswitch: −1.96 mL/min/1.73 m2/year; both p < 0.0001), with steeper decline postswitch (ppre/post = 0.01) in both classic and late‐onset patients. UPCR increased significantly postswitch (ppre/post = 0.003) among classic patients and was stable in both periods among late‐onset patients. GL‐3 trajectories worsened postswitch across phenotypes (ppre/post = 0.0005 classic, 0.02 late‐onset). LPWT was stable preswitch (0.07 mm/year, p = 0.25) and decreased postswitch (−0.51 mm/year, p = 0.0005; ppre/post = 0.0009), primarily among late‐onset patients. IVST and LVMI slopes varied significantly by phenotype. Among classic patients, IVST and LVMI were stable and decreasing, respectively preswitch and increasing postswitch (ppre/post = 0.02 IVST, 0.01 LVMI). Among late‐onset patients, IVST significantly decreased postswitch (ppre/post = 0.0003); LVMI was stable over time (ppre/post = 0.89). Ultimately, eGFR and GL‐3 trajectories worsened postswitch across phenotypes, while UPCR and cardiac measures worsened among classic and stabilized/improved among late‐onset patients. These findings indicate variability in long‐term outcomes after switching from ERT to migalastat, underscoring the importance of careful monitoring.
Restoring galactose metabolism without restoring GALT rescues both compromised survival in larvae and an adult climbing deficit in a GALT‐null D. Melanogaster model of classic galactosemia
Authors: Daenzer Jennifer M. I. , Druss Jared J. , Fridovich‐Keil Judith L.
Published: July 2024

Classic galactosemia (CG) is an autosomal recessive disorder that results from profound deficiency of galactose‐1‐phosphate uridylyltransferase (GALT), the middle enzyme in the highly conserved Leloir pathway of galactose metabolism. That galactose metabolism is disrupted in patients with CG, and in GALT‐null microbial, cell culture, and animal models of CG, has been known for many years. However, whether the long‐term developmental complications of CG result from disrupted galactose metabolism alone, or from loss of some independent moonlighting function of GALT, in addition to disrupted galactose metabolism, has been posed but never resolved. Here, we addressed this question using a GALT‐null Drosophila melanogaster model of CG engineered to express uridine diphosphate (UDP)‐glucose/galactose pyrophosphorylase (UGGP), a plant enzyme that effectively bypasses GALT in the Leloir pathway by converting substrates uridine triphosphate (UTP) plus galactose‐1‐phosphate (gal‐1P) into products UDP‐galactose plus pyrophosphate (PPi). While GALT and UGGP share one substrate (gal‐1P) and one product (UDP‐galactose), they are structurally and evolutionarily unrelated enzymes. It is therefore extremely unlikely that they would also share a moonlighting function. We found that GALT‐null flies expressing UGGP showed not only partial rescue of metabolic abnormalities and acute larval sensitivity to dietary galactose, as expected, but also full rescue of an adult motor deficit otherwise seen in this model. By extension, these results may offer insights to the underlying bases of at least some acute and long‐term complications experienced by patients with CG.
Successful endoscopic submucosal dissection of an esophageal granular cell tumor in a pediatric patient: A case report and a therapeutic insight
Authors: Dogom Sara Al , Thongpiya Jerapas , Elmassry Marawan , Feist Mark , Sharma Meenu , Rateb George
Published: July 2024

Esophageal granular cell tumors (GCTs) are rare mesenchymal neoplasms that originate from the Schwann cells of the neural sheath in the esophageal wall. Esophageal GCTs represent approximately 2% of all GCTs. Most cases of esophageal GCT occur in adults with few cases reported in pediatric patients. Although typically benign, these tumors can occasionally exhibit malignant behavior, necessitating timely and appropriate intervention. Traditionally, surgical resection was considered for treatment, nonetheless, considering the invasive nature of such interventions, endoscopic approaches have been developed for diagnosis and treatment. Endoscopic approaches have been shown to lead to serious complications at times, such as incomplete resection or perforation. Here, we present a successful application of endoscopic submucosal dissection in the treatment of an adolescent female patient with esophageal GCT which was discovered during her prior esophagogastroduodenoscopy for vomiting.
Identification of water transitions using a combination of moisture sorption characteristics and dielectric properties of different parts of jasmine rice (Oryza sativa)
Authors: Changbandit Pitiwat , Santalunai Samran , Thongsopa Chanchai , Phahom Traiphop
Published: July 2024

BACKGROUND

In this work, water transition points (first transition: monolayer–multilayer water; and second transition: multilayer–free and solvent water) of different parts of jasmine rice including white rice, brown rice and bran were identified through the integration of sorption isotherm and dielectric properties data. Desorption isotherm data were fitted to four established models to select the optimal model for describing the sorption behaviors. Then, dielectric properties such as dielectric constant (ε′) and dielectric loss factor (ε″) were measured across various moisture content levels within the frequency range of 200–20 000 MHz.

RESULTS

A type III isotherm was observed for all samples and the Peleg model was the best fit with the experimental data. Monolayer moisture content of the samples, estimated using the GAB model, ranged from 3.25% to 4.17% dry basis. For dielectric properties, frequency and moisture dependencies were evident for all sample types. Moreover, the sorption isotherm models effectively described the relationship between water activity (aw) and dielectric properties as reflected by their goodness of fit, and their strong correlation through principal component analysis and Pearson's correlation results.

CONCLUSION

The first water transition occurs at aw values of 0.11, 0.12, and 0.22, while the second transition appears at aw values of 0.9, 0.9 and 0.75–0.85 for white rice, brown rice and bran, respectively. This knowledge will be useful for food processors, providing insights into the optimization of food processing and storage conditions to extend food products' shelf life. © 2024 Society of Chemical Industry.
Brown seaweed as a food ingredient contributing to an adequate but not excessive amount of iodine in the European diet. A case study with bread
Authors: Ballance Simon , Rieder Anne , Arlov Øystein , Knutsen Svein Halvor
Published: July 2024

BACKGROUND

The large amounts of iodine in brown seaweeds may contribute towards an adequate iodine intake, but also pose a food safety risk. In the current work we estimate the maximum amount of the cultivated brown seaweeds Saccharina latissima and Alaria esculenta (blanched and non‐blanched) that can be added to white loaf‐type wheat‐bread so European consumers are protected against excessive chronic intakes. We use data for high‐level consumers of bread with special ingredients added from the EFSA comprehensive European food consumption database to construct a conservative risk management model. We bake prototype seaweed bread and use the output from the model to assess exposure to iodine and trace metals. We also assess some bread quality parameters such as sensory characteristics, crumb firmness and specific volume.

RESULTS

The maximum level of iodine in bread that would mitigate the European consumer from excess intakes was 857 μg I kg−1 bread. Assuming a typical 60% wheat flour per kilogram of bread, a maximum amount of 11.3 g of dried blanched A. esculenta (115 mg I kg−1 dry weight) could be incorporated per kilogram of wheat flour into the bread recipe whilst for non‐blanched S. latissima, which contained 3500 mg I kg−1 dry weight, only a minuscule 350 mg of seaweed was the limit. For prototype breads, seaweed addition had no significant impact on the specific volume and crumb firmness. Levels of cadmium and arsenic in the bread were also of low toxicological concern.

CONCLUSION

A maximum 1–2% brown seaweed of total flour weight could be added to bread to contribute towards European consumers’ adequate iodine intake without overexposure. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
A case of miliaria profunda after excessive sweating during a summer vacation
Authors: Palacio Ariana , Medrano Cebrian Karla , Koch Lin‐Kristin , Bierhoff Erhard , Bonness Sonja , Reinhold Uwe
Published: July 2024

We present the case of an otherwise healthy 34‐year‐old man of Asian descent diagnosed with miliaria profunda after a 6‐week history of generalised anhidrosis after a trip to Mallorca in the summer.
Gut microbiota‐derived metabolite trimethylamine N‐oxide aggravates cognitive dysfunction induced by femoral fracture operation in mice
Authors: Xiong Ying , Pu Ya‐Nan , Li Li‐Ya , Su Yang , Niu Jia‐Yuan , Xiao Zhao‐Yang
Published: July 2024

An increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a role in its pathogenesis. Among these, the specific effects of trimethylamine N‐oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO‐induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ‐free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO‐related POCD and improving the quality of life for elderly patients.
Modern multiligament knee injury surgical reconstruction techniques can achieve excellent knee function and patient satisfaction, with low complication rates
Authors: Mayne Alistair I. W. , Ebert Jay R. , Edwards Peter K. , Davies Peter S. E. , Evans Robert , Aujla Randeep S. , Malik Shahbaz S. , Grant Michael J. , Dalgleish Stephen , Gohil Satyen , D'Alessandro Peter
Published: July 2024

Purpose

To report on the recovery of strength and functional capacity symmetry following multiligament knee surgical reconstruction (MLKR), as well as the capacity of athletes to return to sport.

Methods

This prospective cohort study recruited 47 patients undergoing MLKR between February 2018 and July 2021. Forty patients had full outcome assessment postoperatively at 6, 12 and 24 months and were included in the analysis, 75% were knee dislocation one injuries and 60% were injured playing sport. Patient‐reported outcome measures (PROMs) assessed included the International Knee Documentation Committee score, the Knee Outcome Survey, the Lysholm Knee Score and the Tegner Activity Scale (TAS). Patient satisfaction was also assessed. Objective assessment included assessment of active knee flexion and extension range of motion (ROM), the single (single horizontal hop for distance [SHD]) and triple (triple horizontal hop for distance [THD]) hop tests for distance and peak isokinetic knee flexor/extensor torque.

Results

All PROMs significantly improved (p < 0.001) from presurgery to 24 months postsurgery. At 24 months, 70% of patients were satisfied with their sports participation. Active knee flexion (p < 0.0001) and extension (p < 0.0001) ROM significantly improved over time, as did the limb symmetry indices (LSIs) for the SHD (p < 0.0001), THD (p < 0.0001), peak knee extensor (p < 0.0001) and flexor (p = 0.012) torque. While LSIs for the SHD, THD and knee flexor strength tended to plateau by 12 months, knee extensor strength continued to improve from 12 to 24 months.

Conclusions

The majority of patients undergoing modern MLKR surgical techniques and rehabilitation can achieve excellent knee function, with low complication rates.

Level of Evidence

Level IV.
The deltoid ligament complex is reliably visualised as four fascicles in two layers with 3D volumetric MRI in the ankles of 20 asymptomatic volunteers
Authors: Fernandez Miguel A. , Lee Justin , Calder James , Katakura Mai , Jones Mary , Dalmau‐Pastor Miki
Published: July 2024

Purpose

The anatomy of the deltoid ligament is complex. There is agreement on the presence of superficial and deep layers but the number and frequency of fascicles remains controversial. Identifying injuries to specific components of the deltoid ligament may inform decision‐making on their management. The anatomy was reviewed to establish the number and dimension of fascicles visible with three‐dimensional (3D) volumetric magnetic resonance images (MRI).

Methods

Twenty ankles from asymptomatic healthy volunteers were imaged with 3D volumetric MRI. The presence of individual fascicles was recorded and measured in 3D.

Results

The median age of participants was 26 years (range: 20–37) of which 13 (65%) were female. All 20 ankles had a deltoid ligament formed of four fascicles in two layers: three fascicles in the superficial layer; tibionavicular (mean dimensions 22.5 × 10.0 × 2.4 mm), tibiospring (16.6 × 6.7 × 1.9 mm) and tibiocalcaneal (23.8 × 4.6 × 1.8 mm) and a deep layer consisting of the tibiotalar fascicle, which could be divided into two parts: anterior tibiotalar (mean dimensions 10 × 5.6 × 4.1 mm) and the significantly larger posterior tibiotalar (14.2 × 13.8 × 17.5 mm, p < 0.01). There were no additional fascicles observed.

Conclusions

The deltoid ligament complex was consistently visualised as four fascicles (tibionavicular, tibiospring, tibiocalcaneal, tibiotalar) in two layers (superficial and deep) in all 20 ankles. The posterior part of the tibiotalar fascicle was the thickest of all the fascicles in the deltoid ligament. It is, therefore, possible to accurately identify the components of the deltoid ligament, and 3T MRI can be used to assess fascicle‐specific injury, which will guide treatment and rehabilitation.

Level of Evidence

Level III.
Delayed Facial Nerve Dysfunction Following CyberKnife® Radiosurgery for Vestibular Schwannoma
Authors: Johns J. Dixon , Ahn Peter H. , Rashid Abdul X. , Conroy Dylan R. , Chisolm Paul F. , Kim H. Jeffrey
Published: July 2024

Objective

The incidence and risk factors for facial nerve dysfunction (FND) following CyberKnife® therapy for vestibular schwannoma (VS) remain poorly understood. This study investigates whether differential radiation doses to vulnerable segments of the facial nerve may be associated with FND outcomes.

Methods

Patients were identified who underwent CyberKnife® radiosurgery for VS at a single institution. Basic demographics, tumor characteristics, and facial nerve function were collected. Total radiation doses to tumor, internal auditory canal (IAC), and labyrinthine segment of facial nerve (LSFN) were evaluated.

Results

Six out of 64 patients experienced FND following CyberKnife® treatment for VS (9.38%, 6/64). Patients with FND were compared to those without FND (control). Of the 64 patients, complete radiation records were obtained for 30 patients (6 FND vs. 24 control). There were no significant differences in demographic or tumor characteristics between control and FND cohorts. More severe FND (HB ≥ 4) had significantly larger tumors (3.74 vs. 1.27 cm3, p = 0.037) with directionally decreased time to FND (3.50 vs. 33.5 months, p = 0.106) than patients with HB < 4, respectively. There were directionally, nonsignificant differences between maximum radiation doses to the LSFN (2492.4 vs. 2557.0 cGy, p = 0.121) and IAC (2877.3 vs. 2895.5 cGy, p = 0.824) between the control and FND cohorts, respectively.

Conclusions

FND may represent an underrecognized sequelae of CyberKnife® radiosurgery for VS that can occur many months following treatment. Further studies are needed to elucidate the effect of differential radiation exposure to the facial nerve with FND following treatment.

Level of Evidence

3 (Retrospective Cohort Study) Laryngoscope, 134:5080–5086, 2024
Insight into the spatial nature of the urban sprawl phenomenon in European capitals
Authors: Grabowska Wiktoria , Kukulska‐Kozieł Anita , Noszczyk Tomasz
Published: July 2024

This research provides a brief insight into the spatial nature of urban sprawl in functional urban areas (FUAs) of European capitals, as opposed to most investigations into urban growth that focus on case studies. Its purpose is to identify European capitals that grow the most and characterize the spatial aspect of urban sprawl and dynamics of ensuing land‐cover change between 2006, 2012, and 2018. We employed open data from the Urban Atlas, which we processed with spatial analyses and the NUASI (Normalized Urban Atlas Sprawl Indicator) to quantify the scale of urban sprawl in the investigated areas. The results demonstrate the most dynamic growth for Central and Eastern European and Iberian Peninsula capitals, while it seems to be slowing down in other Western European and Balkan countries. Moreover, we found out that FUAs of European capitals differ in terms of the scale and pace of uncontrolled urban sprawl. The results of our comparative analyses are relevant to urban development because they can identify areas exhibiting various scales and paces of urban sprawl to take targeted actions depending on the needs defined by decision‐makers and strategies.
Nonendemic rhinoscleroma: An unusual manifestation of the trachea
Authors: Celidonio Joseph , Bahethi Rohini , Malhotra Raj , Sangappa Suchitra , Kaye Rachel
Published: July 2024

Objectives

Rhinoscleroma is classically described as a chronic granulomatous disease caused by Klebsiella rhinoscleromatis which primarily affects the nose and nasopharynx. When present, tracheal manifestations will be seen late in the disease course rather than on initial presentation. We describe a rare case of nonendemic rhinoscleroma that presented with tracheal lesions as an initial manifestation of disease.

Methods

Case report and literature review.

Results

An 88‐year‐old male presented with longstanding dysphonia. Flexible laryngoscopy demonstrated a septal perforation and diffuse glottic lesions. CT neck demonstrated a nonobstructive polypoid tracheal lesion and mucosal thickening of the paranasal sinuses. Biopsy confirmed an atypical lympho‐histiocytic proliferation and microorganisms within macrophages on Grocott methenamine silver and Steiner stains consistent with rhinoscleroma. He was referred for rheumatology and pulmonology consultation.

Conclusion

Systemic diseases rarely affect the trachea, and even less frequently is a tracheal lesion identified as the initial manifestation of disease. The most common systemic diseases that affect the trachea include relapsing polychondritis, granulomatosis with polyangiitis, amyloidosis, and inflammatory bowel disease. The literature surrounding nasolaryngotracheal rhinoscleroma is limited, especially in nonendemic areas. It is necessary to include unusual etiologies of airway lesions in the differential diagnosis, which warrants comprehensive airway evaluation including biopsy.

Level of Evidence

4.
Integrated Resonant Electro‐Optic Comb Enabled by Platform‐Agnostic Laser Integration
Authors: Luntadila Lufungula Isaac , Shams‐Ansari Amirhassan , Renaud Dylan , Op de Beeck Camiel , Cuyvers Stijn , Poelman Stijn , Billet Maximilien , Roelkens Gunther , Lončar Marko , Kuyken Bart
Published: July 2024

The field of integrated photonics has significantly impacted numerous fields including communication, sensing, and quantum physics owing to the efficiency, speed, and compactness of its devices. However, the reliance on off‐chip bulk lasers compromises the compact nature of these systems. While silicon photonics and III‐V platforms have established integrated laser technologies, emerging demands for ultra‐low optical loss, wider bandgaps, and optical nonlinearities necessitate other platforms. Developing integrated lasers on less mature platforms is arduous and costly due to limited throughput or unconventional process requirements. In response, a novel platform‐agnostic laser integration technique is proposed, utilizing a singular design and process flow, applicable without modification to a diverse range of platforms. Leveraging a two‐step micro‐transfer printing method, nearly identical laser performance is achieved across platforms with refractive indices between 1.7 and 2.5. Experimental validation demonstrates strikingly similar laser characteristics between devices processed on lithium niobate and silicon nitride platforms. Furthermore, the integration of a laser with a resonant electro‐optic comb generator on the thin‐film lithium niobate platform is showcased, producing over 80 comb lines spanning 12 nm. This versatile technique transcends platform‐specific limitations, facilitating applications like microwave photonics, handheld spectrometers, and cost‐effective Lidar systems, across multiple platforms.
Functional Impact of the FADS1 rs174546 Single Nucleotide Polymorphism on Serum Lipid Levels: Insights from Molecular Mechanisms and Therapeutic Perspectives in Korean Population
Authors: Lee Kyun‐Hee , Kim Soon‐Hee , Park Sunmin , Jang Hyun‐Jun , Kim Min Jung , Yang Hye Jeong , Hur Haeng Jeon , Kim Jin Hee , Kim Myung‐Sunny
Published: July 2024

Scope

Single nucleotide polymorphisms (SNP) in the fatty acid desaturase 1 (FADS1) gene is suggested as risk factor of metabolic diseases in genome‐wide association studies (GWAS). This study hypothesized that FADS1_rs174546T associates with serum triglycerides (TG) in Korean Genome and Epidemiology Study (KoGES). In addition, functional study of SNP genotypes in cultured cells is performed.

Methods and results

FADS1_rs174546T is associated with high level of serum TG (effect size of variant: 6.48 ± 1.84 mg dL−1) in Korean individuals (normotriglyceridemia, n = 5128; hypertriglyceridemia, n = 3714). Functional study in cells with FADS1_rs174546T, shows reduced transcriptional activity, when compared with rs174546C. MiR‐6728‐3p, which is predicted to bind with rs174546T, decreases transcriptional activity of rs174546T but not in rs174546C, and it is reversed by miR‐6728‐3p inhibitor. Formononetin is selected as binding molecule to 3′‐UTR of FADS1 and increases luciferase activity in both rs174546 (C/T). Moreover, formononetin compensates for the reduced luciferase activity by rs174546T and miR‐6728‐3p. Formononetin also increases endogenous FADS1 expression and long‐chain polyunsaturated fatty acid (LC‐PUFA) ratio.

Conclusion

FADS1_rs174546T is a crucial risk factor for hypertriglyceridemia in the Koreans potentially through the interaction with miR‐6728‐3p. Formononetin can be a potent dietary intervention to prevent and improve hypertriglyceridemia in both rs174546 (C/T) populations.
Measuring psychological distress using the 12‐item general health questionnaire and the six‐item Kessler psychological distress scale. Psychometric comparison and equipercentile equating of the two scales
Authors: Lundin Andreas , Muwonge Joseph Junior , Lalouni Maria , Åhlén Johan
Published: July 2024

Objectives

This study aimed to examine if the General Health Questionnaire (GHQ)‐12 and Kessler 6 (K6) assess the same underlying construct and to develop a score conversion table for the two scales.

Methods

A random sample of 4303 people who completed both the GHQ‐12 and K6 in 2021 were analyzed. Exploratory bifactor analysis evaluated if both scales measured the same construct, and Rasch analysis assessed item severities. The scales were transformed using Equipercentile equivalence for comparability and score conversion. Agreement was estimated with Cohen's Kappa coefficient, along with raw positive and negative agreement.

Results

We found that the two scales measure the same phenomenon to the extent that they can be made equivalent. Conversion tables between GHQ‐12 and K6 are presented. Applying the commonly used cut‐off of ≥3 on the GHQ‐12 bi‐modal scoring, we found that the best corresponding cut‐off on the K6 would be ≥8. The prevalence of psychological distress was then 22% with GHQ‐12% and 21% with K6.

Conclusions

The GHQ‐12 and K6 measure the same construct and corresponding cut‐off scores on one scale were found for the other scale. This is valuable for longitudinal studies or time series where one scale has replaced the other scale.
Multi‐scale mechanics of polydisperse granular materials: From micro‐scale and wave propagation experiments to DEM analysis
Authors: Reddy Nallala S. C. , He Huan , Senetakis Kostas
Published: July 2024

This paper presents a multiscale experimental study integrated with numerical simulations examining the mechanics of polydisperse granular mixtures composed of coarse‐grained particles mixed with varying percentages of fines. The study includes macroscale wave propagation tests using bender elements on isotopically compressed granular samples to investigate the stiffness variation with changes in size ratio (SR) and fines content (FC). Empirical equations were developed to predict stiffness based on the experimental data, using the concept of equivalent void ratio to represent the influence of void ratio on stiffness. A newly introduced parameter called size disparity indicator was used to consider the coupled effects of size disparity and fines content on stiffness. Microscale assessment of the individual contacting grains revealed that stiffness (at grain scale) is affected by changes in grain size, even when the SR is less than 6, however, the experimental observations of the shear modulus behavior from the macroscale test results reveal minimal effect of FC. Furthermore, numerical simulations using the discrete element method were conducted on the polydisperse granular mixtures to demonstrate the coupled effect of SR and FC on the structural matrix formation, thereby influencing the force transfer among contacts resulting in varying stiffness behavior. Our findings provide valuable insights into the behavior of polydisperse granular mixtures in engineering applications.