bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of frequency and amplitude dependence on the cyclic degradation of polyurethane foams
Authors: Foster Moira M. , Morrison Daniel C. , Landauer Alexander K. , Herynk Mark D. , Lamberson Leslie E.
Published: June 2024

Many energy absorption applications utilize flexible polymeric foams for their viscoelastic properties. It is desired that the material will perform consistently across repeated compression cycles. This study examines the effect of fatigue at low strain rates on the viscoelasticity of open‐cell polyurethane foam. Six polyurethanes of the same base composition with two porosities (70% and 80%) and three chemical indexes (79i, 100i, and 121i) are tested. Large deformation cyclic compression of the foams is conducted on a universal testing system (UTS). These data are then post‐processed leveraging dynamic mechanical analysis Fourier transform rheology to characterize changes in the viscoelasticity of the materials over fatigue cycles. Results show that foams can increase or decrease in stiffness up to 10% over 104 cycles. Specifically, higher chemical index, higher excitation frequency, and larger excitation amplitude correlate with a more pronounced decrease in stiffness. Damping can also change by 15% and correlates with chemical index and excitation frequency. Consequently, the findings suggest that internal foam structure and bulk material properties as well as applied loading parameters affect the viscoelastic fatigue response of flexible polymeric foams.
Fluid Financing of Water Utility Infrastructure With WIFIA
Authors: Franco Sean , Carpenter Adam T.
Published: June 2024

Key Takeaways

The Water Infrastructure Finance and Innovation Act (WIFIA) is a US Environmental Protection Agency finance program that has gained bipartisan support over its decade of existence.

WIFIA is designed to accelerate nationally or regionally significant infrastructure projects by providing low‐interest loans for water projects.

Loan amounts vary across project types, but not among project types per capita.

Generally, stormwater and drinking water project types have lower loan amounts, while wastewater and reuse project types have a wider range.
Dichorionic diamniotic twin pregnancy after preimplantation genetic testing and single blastocyst transfer
Authors: Huang Qiuxiang , Yan Wei , Mao Lihua , Wang Caixia , Lin Juan , Liu Yun , Wang Zhihong
Published: June 2024

Background

In addition to the potential for multiple pregnancies, natural conception occurring in preimplantation genetic testing (PGT) increases undesired genetic risk. Some studies showed that a dichorionic diamniotic twin pregnancy after a single blastocyst transfer could be caused by embryo splitting or concurrent spontaneous conception.

Case

We describe a patient undergoing PGT who had a dichorionic diamniotic twin pregnancy after single blastocyst transfer in a natural cycle. In this case, we recommended to determine genetic status of the twins by prenatal diagnosis. The results showed that karyotype, chromosome copy number variation, and parental ACAT1 variation of the twins were all normal and similar. To investigate the origin of pregnancy, we used the genotype data of single‐nucleotide polymorphisms typical of genome‐wide association studies. Dizygotic twins were inferred by robust estimation of kinship coefficients, which confirmed the occurrence of a spontaneous conception.

Conclusions

This case strengthens the importance of genetic counseling to inform couples with reproductive genetic risk, such as those who undergo PGT, that intercourse should be avoided, especially in natural transfer cycles. Moreover, prenatal diagnosis remains essential and is strongly recommended to avoid genetic risks.
C2H2 proteins: Evolutionary aspects of domain architecture and diversification
Authors: Bonchuk Artem N. , Georgiev Pavel G.
Published: June 2024

The largest group of transcription factors in higher eukaryotes are C2H2 proteins, which contain C2H2‐type zinc finger domains that specifically bind to DNA. Few well‐studied C2H2 proteins, however, demonstrate their key role in the control of gene expression and chromosome architecture. Here we review the features of the domain architecture of C2H2 proteins and the likely origin of C2H2 zinc fingers. A comprehensive investigation of proteomes for the presence of proteins with multiple clustered C2H2 domains has revealed a key difference between groups of organisms. Unlike plants, transcription factors in metazoans contain clusters of C2H2 domains typically separated by a linker with the TGEKP consensus sequence. The average size of C2H2 clusters varies substantially, even between genomes of higher metazoans, and with a tendency to increase in combination with SCAN, and especially KRAB domains, reflecting the increasing complexity of gene regulatory networks.
Renal cell carcinoma and risk of second primary cancer: A Danish nationwide cohort study
Authors: Bengtsen Maria B. , Farkas Dóra K. , Sørensen Henrik T. , Nørgaard Mette
Published: June 2024

Aim

To examine the risk of second primary cancer in patients with incident renal cell carcinoma (RCC).

Methods

We identified all patients diagnosed with incident RCC during 1995–2019, using population‐based Danish medical registries. Patients were followed from the date of RCC diagnosis until any second primary cancer diagnosis, death, emigration, or December 31, 2019, whichever came first. We computed the absolute risk, standardized incidence ratio (SIR), and excess absolute risk of second primary cancer, with 95% confidence intervals (CIs), among patients with RCC compared to the general population.

Results

The absolute 1‐ and 20‐year risks of any second primary cancer were 2.8% and 17.8%, respectively. Within 1 year after RCC diagnosis, we detected 20 excess cancer cases per 1000 person‐years (PY) (SIR, 2.3; 95% CI: 2.1–2.6). Moreover, we detected an additional four excess cancer cases per 1000 PY during 1 to <5 years of follow‐up (SIR, 1.3; 95% CI: 1.2–1.4), and 6 per 1000 PY beyond 5 years of follow‐up (SIR, 1.4; 95% CI: 1.3–1.5). The sustained elevated cancer risk beyond 1 year of follow‐up was mainly attributed to excess risk of lung and bladder cancer. The risk of second primary cancer was higher in 2006–2019 than in 1995–2005, but only during the first year of follow‐up.

Conclusion

Patients with incident RCC have a sustained 40% elevated long‐term risk of second primary cancer, compared with the general population. This increased risk is mainly attributed to lung and bladder cancer.
Comparing in vitro cytotoxic drug sensitivity in colon and pancreatic cancer using 2D and 3D cell models: Contrasting viability and growth inhibition in clinically relevant dose and repeated drug cycles
Authors: Tidwell Tia R. , Røsland Gro , Tronstad Karl Johan , Søreide Kjetil , Hagland Hanne R.
Published: June 2024

Background

In vitro drug screening that is more translatable to the in vivo tumor environment can reduce both time and cost of cancer drug development. Here we address some of the shortcomings in screening and show how treatment with 5‐fluorouracil (5‐FU) in 2D and 3D culture models of colorectal cancer (CRC) and pancreatic ductal adenocarcinomas (PDAC) give different responses regarding growth inhibition.

Methods

The sensitivity of the cell lines at clinically relevant 5‐FU concentrations was monitored over 4 days of treatment in both 2D and 3D cultures for CRC (SW948 and HCT116) and PDAC (Panc‐1 and MIA‐Pa‐Ca‐2) cell lines. The 3D cultures were maintained beyond this point to enable a second treatment cycle at Day 14, following the timeline of a standard clinical 5‐FU regimen.

Results

Evaluation after one cycle did not reveal significant growth inhibition in any of the CRC or PDAC 2D models. By the end of the second cycle of treatment the CRC spheroids reached 50% inhibition at clinically achievable concentrations in the 3D model, but not in the 2D model. The PDAC models were not sensitive to clinical doses even after two cycles. High content viability metrics point to even lower response in the resistant PDAC models.

Conclusion

This study reveals the limitations of testing drugs in 2D cancer models and short exposure in 3D models, and the importance of using appropriate growth inhibition analysis. We found that screening with longer exposure and several cycles of treatment in 3D models suggests a more reliable way to assess drug sensitivity.
Electrochemical/Electrochemiluminescence Sensors Based on Vertically‐Ordered Mesoporous Silica Films for Biomedical Analytical Applications
Authors: Fan Xue , Wu Jiayi , Zhang Tongtong , Liu Jiyang
Published: June 2024

Vertically‐ordered mesoporous silica films (VMSF, also named as silica isoporous membranes) have shown tremendous potential in the field of electroanalytical sensors due to their unique features in terms of controllable and ultrasmall nanopores, high molecular selectivity and permeability, and mechanical stability. This review will present the recent progress on the biomedical analytical applications of VMSF, focusing on the small biomolecules, diseases‐related biomarkers, drugs and cancer cells. Finally, conclusions with recent developments and future perspective of VMSF in the relevant fields will be envisioned.
COVID‐19‐induced immune thrombocytopenia management approach: A case report and literature review
Authors: Alahwal Hatem Mahmoud , Alsharif Mansour Hani , Alsharif Mada Hani , Almohammadi Abdullah Talal , Al‐Marzouki Adel Fahad , Barefah Ahmed Saleh , Bahashwan Salem Mohammad , Radhwi Osman Omer , Damanhouri Ghazi Abdullah
Published: June 2024

Key Clinical Message

Vincristine therapy can be effective in refractory Immune thrombocytopenia (ITP) following COVID‐19 vaccination. Our case report highlights the need for further research to establish standard management guidelines for COVID‐19‐vaccine‐associated ITP.

Adult immune thrombocytopenia (ITP) can occur as a rare complication following several viral infections or a rare adverse event or complication of vaccination. In this paper, we report a case of a 39‐year‐old male patient with severe refractory ITP that began 4‐weeks after receiving his third (booster) dose of the COVID‐19 vaccine (BNT162b2, Pfizer‐BioNTech). He was given oral dexamethasone 40 mg daily for 4 days followed by prednisone at 1 mg/kg (85 mg daily) for 10 days. In the following weeks, we attempted several other lines of therapy to treat his ITP, including anti‐RhD immunoglobulin, which, unfortunately, caused moderate hemolysis requiring packed red blood cell transfusion, intravenous immunoglobulin (given at a subtherapeutic dose of 0.4 g/kg for only 1 day since it was not available), rituximab, and eltrombopag. The patient, unfortunately, showed no response to any of these treatments. This was an indicator to initiate salvage therapy with vincristine 2 mg weekly for 3 weeks. The patient's platelet count started to increase remarkably during the third week of vincristine and normalized after 4 weeks. We review the findings, clinical characteristics, and management approaches that were reported in the literature regarding COVID‐19‐vaccine‐induced ITP. More in‐depth research is needed to delineate standard guidelines for the management of such cases. This report underscores the importance of resorting to vincristine and eltrombopag as great options for severe and refractory ITP related to the COVID‐19 vaccine.
Comparative study of the thermo‐catalytic reforming of agricultural and forest residue and advanced characterization of final products in a cold climate
Authors: Dhakal Bijay , Kurian Vinoj , Bhattacharjee Neelanjan , Gupta Rajender , Olfert Jason , Kostiuk Larry , Hornung Andreas , Kumar Amit
Published: June 2024

Global agricultural and forest residues hold promise for renewable fuel production through thermo‐catalytic reforming (TCR). Limited data exists on TCR outcomes for regions known for cold conditions like Canada. This study used a 2 kg h−1 TCR unit for the intermediate pyrolysis/reforming of agricultural (wheat straw pellet, WSP) and forest (softwood pellet, SWP) residues. Maximum bio‐oil yields were 8.43% for wheat straw pellets and 7.99% for softwood pellets at 400 and 500°C reactor and reformer temperatures. Feedstock, bio‐oil, and biochar properties were analyzed through proximate and ultimate analysis. At 550°C reactor and 700°C reforming temperatures, 70.73% of the wheat straw pellet‐based gas yield contained 36.11 vol.% H2 and 11.08 vol.% CH4, giving a higher heating value (HHV) of 12.54 MJ kg−1. A high concentration of CH4 (22.02 vol.%) in the softwood pellet‐based gas gave an HHV of 17.94 MJ kg−1. The low viscosity (3.9 mPa · s−1) and total acid number (7.3 mg KOH g−1) wheat straw pellet‐based bio‐oil had an O/C molar ratio of 0.09 and an HHV of 35.80 MJ kg−1. The 400/600°C reactor/reformer temperatures gave the lowest area percentage of mono‐aromatic (16 vol.%) and polycyclic aromatic (11.20 vol.%) compounds in the softwood pellet bio‐oil. The O/C molar ratio (0.5–0.6) in softwood pellet biochar elevated the higher heating value from 32.37 to 34.57 MJ kg−1. The study results guide optimal TCR unit operation in cold climates like Canada with local feedstocks, emphasizing its notable hydrogen production over bio‐oil and biochar.
MEK inhibitors and DA‐Raf, a dominant‐negative antagonist of the Ras–ERK pathway, prevent the migration and invasion of KRAS‐mutant cancer cells
Authors: Matsuda Aoi , Masuzawa Ryuichi , Takahashi Kazuya , Takano Kazunori , Endo Takeshi
Published: June 2024

The Ras‐induced ERK pathway (Raf–MEK–ERK signaling cascade) regulates a variety of cellular responses including cell proliferation, survival, and migration. Activating mutations in RAS genes, particularly in the KRAS gene, constitutively activate the ERK pathway, resulting in tumorigenesis, cancer cell invasion, and metastasis. DA‐Raf1 (DA‐Raf) is a splicing isoform of A‐Raf and contains the Ras‐binding domain but lacks the kinase domain. Consequently, DA‐Raf antagonizes the Ras–ERK pathway in a dominant‐negative manner and can serve as a tumor suppressor that targets mutant Ras protein‐induced tumorigenesis. We show here that MEK inhibitors and DA‐Raf interfere with the in vitro collective cell migration and invasion of human KRAS‐mutant carcinoma cell lines, the lung adenocarcinoma A549, colorectal carcinoma HCT116, and pancreatic carcinoma MIA PaCa‐2 cells. DA‐Raf expression was silenced in these cancer cell lines. All these cell lines had high collective migration abilities and invasion properties in Matrigel, compared with nontumor cells. Their migration and invasion abilities were impaired by suppressing the ERK pathway with the MEK inhibitors U0126 and trametinib, an approved anticancer drug. Expression of DA‐Raf in MIA PaCa‐2 cells reduced the ERK activity and hindered the migration and invasion abilities. Therefore, DA‐Raf may function as an invasion suppressor protein in the KRAS‐mutant cancer cells by blocking the Ras–ERK pathway when DA‐Raf expression is induced in invasive cancer cells.
Cytologic features of differentiated high‐grade thyroid carcinoma: A multi‐institutional study of 40 cases
Authors: Torous Vanda F. , Jitpasutham Tikamporn , Baloch Zubair , Cantley Richard L. , Kerr Darcy A. , Liu Xiaoying , Maleki Zahra , Merkin Ross , Nosé Vania , Pantanowitz Liron , Resta Isabella Tondi , Rossi Esther D. , Faquin William C.
Published: June 2024

Background

Differentiated high‐grade thyroid carcinoma (DHGTC) is recently recognized by the World Health Organization (WHO) as a subgroup of thyroid carcinomas with high‐grade features while retaining the architectural and/or cytologic features of well‐differentiated follicular–cell‐derived tumors. The cytomorphology of DHGTC is not well documented despite potential implications for patient triage and management.

Methods

The pathology archives of six institutions were searched for cases diagnosed on resection as “high‐grade thyroid carcinoma” using WHO criteria. The fine‐needle aspiration (FNA) cohort represents a 10‐year period (2013–2023); all were reviewed to confirm DHGTC classification. The corresponding FNAs were assessed for 32 cytomorphologic features.

Results

Forty cases of DHGTC with prior FNA were identified. The mean patient age was 64.2 years. The average lesion size was 4.9 cm, and the majority demonstrated a TI‐RADS score of 4 or 5 (95.2%). Three main high‐grade subsets of DHGTC based on corresponding histology included papillary thyroid carcinoma (65%), follicular carcinoma (22.5%), and oncocytic carcinoma (12.5%). Over 97% of FNA cases were classified as Bethesda category IV or above. Approximately 25% of DHGTC showed cytologic features that included marked cytologic atypia, increased anisonucleosis, large oval nuclei, mitotic activity, or necrosis (p < .05); 68% of DHGTC cases were associated with high‐risk molecular alterations. TERT mutations occurred in 41%, of which 89% of these were associated with a second mutation, usually RAS or BRAF p.V600E.

Conclusions

Cytology has a low sensitivity for DHGTC, although a subset of DHGTCs have cytologic features raising the possibility of a high‐grade thyroid carcinoma. Other findings include high‐risk molecular changes and clinicopathologic features such as older patient age and larger lesion size.
Protodefluorinated Selectfluor® Aggregatively Activates Selectfluor® for Efficient Radical C(sp3)−H Fluorination Reactions
Authors: Yakubov Shahboz , Dauth Bastian , Stockerl Willibald J. , da Silva Wagner , Gschwind Ruth M. , Barham Joshua P.
Published: June 2024

Efficient fluorination reactions are key in the late‐stage functionalization of complex molecules in medicinal chemistry, in upgrading chemical feedstocks, and in materials science. Radical C(sp3)−H fluorinations using Selectfluor® – one of the most popular fluorination agents – allow to directly engage unactivated precursors under mild photochemical or thermal catalytic conditions. However, H−TEDA(BF4)2 to date is overlooked and discarded as waste, despite comprising 95% of the molecular weight of Selectfluor®. We demonstrate that the addition of H−TEDA(BF4)2 at the start of fluorination reactions markedly promotes their rates and accesses higher overall yields of fluorinated products (~3.3 × higher on average across the cases studied) than unpromoted reactions. Several case studies showcase generality of the promotor, for photochemical, photocatalytic and thermal radical fluorination reactions. Detailed mechanistic investigations reveal the key importance of aggregation changes in Selectfluor® and H−TEDA(BF4)2 to fill gaps of understanding in how radical C(sp3)−H fluorination reactions work. This study exemplifies an overlooked reaction waste product being upcycled for a useful application.
Artificial intelligence approaches for phenotyping heart failure in U.S. Veterans Health Administration electronic health record
Authors: Shao Yijun , Zhang Sijian , Raman Venkatesh K. , Patel Samir S. , Cheng Yan , Parulkar Anshul , Lam Phillip H. , Moore Hans , Sheriff Helen M. , Fonarow Gregg C. , Heidenreich Paul A. , Wu Wen‐Chih , Ahmed Ali , Zeng‐Treitler Qing
Published: June 2024

Aims

Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD‐code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients.

Methods and results

The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP‐HF) and non‐HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF‐related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP‐HF as cases (PPV, 0.86; sensitivity, 0.86). From the ‘HF ICD‐code universe’, we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54).

Conclusions

These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.
Phenotype and outcomes according to loop diuretic use in pulmonary arterial hypertension
Authors: Savonitto Giulio , Barbisan Davide , Ameri Pietro , Lombardi Carlo Maria , Monti Simonetta , Driussi Mauro , Gentile Piero , Howard Luke , Toma Matteo , Pagnesi Matteo , Collini Valentino , Bauleo Carolina , Adamo Marianna , D'Angelo Luciana , Nalli Chiara , Giannoni Alberto , Vecchiato Veronica , Di Poi Emma , Airo Edoardo , Metra Marco , Garascia Andrea , Sinagra Gianfranco , Lo Giudice Francesco , Stolfo Davide
Published: June 2024

Aims

The use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of loop diuretics.

Methods and results

Patients diagnosed with PAH between 2001 and 2022 at seven European centres for the management of PAH. According to the median equivalent dose of furosemide in the overall cohort, patients were divided into two subgroups: no/low‐dose loop diuretic and high‐dose loop diuretic. Primary outcome was 5 year all‐cause mortality. Among the 397 patients included, 227 (57%) were treated with loop diuretics. Median daily furosemide equivalent dose was 25 mg, and accordingly patients were divided in no/low dose (i.e. ≤25 mg, n = 257, 65%) vs. high dose (i.e. >25 mg, n = 140, 35%). Patients in the high‐dose group were older, more likely to have comorbidities, and had a more severe disease according to the ESC/ERS risk category. Crude 5 year survival was significantly shorter in patients in the high‐dose group, but after adjustment for age, sex, and risk category, high loop diuretic dose was not significantly associated with the primary outcome.

Conclusions

Use of high dose of loop diuretics in PAH is associated with a higher burden of comorbidities, more severe disease, and worse survival. However, in PAH, the need of high loop diuretic dose is a marker of disease severity and not an independent prognostic factor.
Validity of a motor–cognitive dual‐task agility test in elite youth football players
Authors: Friebe David , Sieland Johanna , Both Hendrik , Giesche Florian , Haser Christian , Hülsdünker Thorben , Pfab Florian , Vogt Lutz , Banzer Winfried
Published: June 2024

Agility, as the ability to react rapidly to unforeseen events, is an essential component of football performance. However, existing agility diagnostics often do not reflect the complex motor–cognitive interaction required on the field. Therefore, this study evaluates the criterion and ecological validity of a newly developed motor–cognitive dual‐task agility approach in elite youth football players and compare it to a traditional reactive agility test. Twenty‐one male youth elite football players (age:17.4 ±0 .6; BMI:23.2 ± 1.8) performed two agility tests (reactive agility, reactive agility with integrated multiple‐object‐tracking (Dual‐Task Agility)) on the SKILLCOURT system. Performance was correlated to motor (sprint, jump), cognitive (executive functions, attention, reaction speed) and football specific tests (Loughborough soccer passing test (LSPT)) as well as indirect game metrics (coaches' rating, playing time). Reactive agility performance showed moderate correlations to attention and choice reaction times (r = 0.48−0.63), as well as to the LSPT (r = 0.51). The dual‐task agility test revealed moderate relationships with attention and reaction speed (r = 0.47−0.58), executive functions (r = 0.45−0.63), as well as the game metrics (r = 0.51−0.61). Finally, the dual‐task agility test significantly differentiated players based on their coaches' rating and playing time using a median split (p < 0.05; d = 0.8–1.28). Motor–cognitive agility performance in elite youth football players seems to be primarily determined by cognitive functions. The integration of multiple object tracking into reactive agility testing seems to be an ecologically valid approach for performance diagnostics in youth football.
Development of a novel dosing paradigm to model diazepam rescue therapy in preclinical seizure and epilepsy models
Authors: Guignet Michelle , White H. Steve , Misra Sunita N. , Carrazana Enrique , Rabinowicz Adrian L.
Published: June 2024

Diazepam is a cornerstone immediate‐use antiseizure rescue therapy that may extend the duration between seizure clusters in people living with epilepsy. However, our mechanistic understanding of intermittent rescue therapy on disease progression is limited by the lack of suitable preclinical models. Specifically, the pharmacokinetics of diazepam varies widely between humans and laboratory animals. Here, we developed a novel repeat rescue therapy dosing paradigm in rats to maintain prolonged therapeutic concentrations seen in humans. Rats received three diazepam doses separated by 1 h (0.75, 1.5, or 3 mg/kg, intraperitoneal); plasma and brains were collected at 10 min and 1, 3, or 6 h following the last dose. Plasma and brain concentrations followed a dose‐dependent increase with peak concentrations following the repeat 3 mg/kg paradigm (180 ng/mL) being equivalent to plasma levels observed in human studies with diazepam nasal spray. Increased brain‐to‐plasma ratios in this paradigm indicate that diazepam accumulation in the brain may be long‐acting at the site of action. Overall, our repeat diazepam dosing paradigm mimics drug concentrations and accumulation seen in humans, offering a preclinical tool to study the impact of benzodiazepine rescue therapy on seizure‐cluster biology in rodent models of epilepsy.

Plain language summary

There is more to learn about how diazepam works in the brains of people who use it only when they have two or more seizures in 24 h (this is called a seizure cluster). Ethical studies in animals can be used to learn more about medicines in the body. In this study, we showed that three doses of diazepam in rats give about the same amount of the drug as one dose for a person. We can now test rats with epilepsy to see how the drug might work in people who take it when needed for seizure clusters.
Cardiovascular risk factor assessment in late‐onset seizures: A study protocol to assess the value of structured intervention
Authors: Larsson David , Åsberg Signild , Sundström Johan , Frid Petrea , Zelano Johan
Published: June 2024

Objective

A growing body of evidence suggests patients with late‐onset seizures are at an increased risk of stroke, but the potential for reducing cardiovascular morbidity through risk factor screening and management is unknown. We aim to determine whether individuals with new‐onset unprovoked seizures after middle age should undergo vascular risk assessment. The long follow‐up needed to assess stroke risk and the known benefit of vascular risk factor modification make a standard RCT logistically and ethically challenging. Instead, we propose and have developed a protocol for a cluster project assessing the effect of vascular risk factor screening in an intervention trial as well as a cohort study.

Methods

Participating neurology clinics will implement standard cardiovascular risk factor assessment into the routine evaluation for individuals aged ≥50 years attending their first specialized consultation after an unprovoked seizure, excluding those with progressive brain disease. The project has two interlinked components: a prospective single group trial, in which risk factor assessment is performed and subsequent management is followed for one year; and a register‐based cohort study examining the long‐term effects of the intervention on a system level by comparing patients attending initial consultations in the 2 years after start of the study, with patients seen in the four preceding years at the same clinics.

Analysis

The primary outcome of the intervention trial is the proportion of patients receiving subsequent pharmacological treatment. The primary outcome of the cohort study is the incidence of acute stroke in the Swedish Stroke Register.

Ethics and Dissemination

Swedish Ethical Review Authority approval (which is valid for 2 years only) will be sought when funding is obtained. The results will be disseminated through peer‐reviewed scientific publications.

Registration Details

The study will be registered at clinicaltrials.gov.

Plain Language Summary

A first seizure in a middle‐aged or older person indicates a higher risk of stroke. It is not known whether investigating and treating blood pressure, blood cholesterol, or similar risk factors after a first seizure is an effective way to prevent stroke. A traditional clinical study would need too many patients and it would be unethical not to treat the control group. We have designed a study in which participating neurology departments change their practice to test and treat vascular risk factors. Patients are then compared to historic controls using registered data.
Magnetic micro‐fluidics in 3D microchannel at the micro‐scale: Unlocking nano‐porous electrode potential for lithium‐ion micro‐batteries
Authors: Ashraf Adeel , Manzoor Tareq , Iqbal Shaukat , Anwar Tauseef , Farooq‐i‐Azam Muhammad , Khan Zeashan , Manzoor Habib Ullah
Published: June 2024

Enhancing the nanosized‐electrolyte's characteristics in Lithium‐driven micro‐batteries (LIMBs) is indispensable to improve the overall efficiency, security, and lifespan of these energy devices, designing nano‐sized electrolyte with a wide electrochemical stability window while keeping them compatible with electrode materials is one of the improvement goals. Battery technologies must go through this optimization process in order to be used practically. A sensing mechanism to keep an eye on the health of Li‐ion energy devices through the magnetization. Magnetic micro‐fluidic patterns that change could be a sign of battery deterioration or other problems with performance. Li‐ion battery health is one application of magnetic sensing that you can do with magnetic sensing. Battery health variations and other performance problems can be found using magnetic mass transport patterns. Present study examines the effects of magnetic field on Eyring–Powel mass transport in nano‐porous channels over a stretching sheet. The principal equations exhibiting the phenomenon are transformed into non‐linear differential equation by second‐order approximation by using a similarity transformation. Furthermore, a semi‐analytic technique named optimal homotopy asymptotic method (OHAM) is used to solve the transformed Eyring–Powell model. The numerical results demonstrated the impact of variations in velocity, skin‐friction coefficient and Sherwood number for the proposed scheme.
Glutathione‐induced hydrogen sulfide enhances drought tolerance in sweet pepper (Capsicum annuum L.)
Authors: Kaya Cengiz , Uğurlar Ferhat
Published: June 2024

Glutathione (GSH) has been studied for its potential to enhance stress tolerance in plant systems, but the role of hydrogen sulfide (H2S) in GSH‐induced water stress tolerance in sweet pepper (Capsicum annuum L.) is still under investigation. This study explores how H2S and GSH modulate water stress tolerance in pepper plants, addressing a research gap. The joint effect of sodium hydrosulfide (NaHS), a donor of H2S, and GSH on water stress tolerance was determined through pre‐treatment with the H2S scavenger 0.1 mM hypotaurine (HT). Pepper seedlings were sprayed with 1.0 mM GSH or GSH + 0.2 mM NaHS once a week, with soil moisture content set at 80% and 40% for full irrigation and water stress conditions for a duration of 2 weeks. The results showed that water stress significantly reduced total plant dry weight, chlorophyll a and b content, Fv/Fm, leaf water potential, and relative water content by 50%, 56%, 33%, 27%, 52%, and 34%, while increasing hydrogen peroxide (H2O2), proline, and H2S levels by 152%, 134%, and77%, respectively. Treatment with GSH and NaHS reduced water stress‐induced H2O2 production and improved plant growth, photosynthetic traits, proline, and the activity of L‐cysteine desulfhydrase (L‐DES), leading to the generation of H2S content. GSH reduced NADPH oxidase (NOX), superoxide dismutase (SOD), and H2O2 but increased glutathione peroxidase (GPX) activities. The interaction of NaHS and GSH led to further reductions in NOX, SOD, and H2O2 values but increased GPX activity. The combined GSH and NaHS treatment increased nitric oxide (NO) production but decreased the activity of S‐nitrosoglutathione reductase (GSNOR), potentially accelerating S‐nitrosylation. Hypotaurine negated the positive impacts of GSH on water stress tolerance by reducing H2S concentration in pepper plants, but this was corrected by the concurrent application of NaHS and GSH + HT. Therefore, water stress tolerance requires H2S.
Cold‐pressed perilla seed oil: Investigating its protective influence on the gut–brain axis in mice with rotenone‐induced Parkinson's disease
Authors: Techaniyom Peerapa , Korsirikoon Chawin , Rungruang Thanaporn , Pakaprot Narawut , Prombutara Pinidphon , Mukda Sujira , Kettawan Aurawan Kringkasemsee , Kettawan Aikkarach
Published: June 2024

Perilla seed oil, derived from a regional plant native to northern Thailand, undergoes cold‐pressing to analyze its bioactive components, notably alpha‐linolenic acid (ALA). ALA, constituting approximately 61% of the oil, serves as a precursor for therapeutic omega‐3 fatty acids, EPA and DHA, with neurodegenerative disease benefits and anti‐inflammatory responses. This study administered different concentrations of perilla seed oil to male C57BL/6 mice, categorized as low dose (LP 5% w/w), middle dose (MP 10% w/w), and high dose (HP 20% w/w), along with a fish oil (FP 10% w/w) diet. An experimental group received soybean oil (5% w/w). Over 42 days, these diets were administered while inducing Parkinson's disease (PD) with rotenone injections. Mice on a high perilla seed oil dose exhibited decreased Cox‐2 expression in the colon, suppressed Iba‐1 microglia activation, reduced alpha‐synuclein accumulation in the colon and hippocampus, prevented dopaminergic cell death in the substantia nigra, and improved motor and non‐motor symptoms. Mice on a middle dose showed maintenance of diverse gut microbiota, with an increased abundance of short‐chain fatty acid (SCFA)‐producing bacteria (Bifidobacteria, Lactobacillus, and Faecalibacteria). A reduction in bacteria correlated with PD (Turicibacter, Ruminococcus, and Akkermansia) was observed. Results suggest the potential therapeutic efficacy of high perilla seed oil doses in mitigating both intestinal and neurological aspects linked to the gut–brain axis in PD.
Sweet pepper extract reduces fat storage in Caenorhabditis elegans by SREBP‐SCD axis based on multiomics analysis
Authors: Wang Junyi , Xu Peng , Liu Xinhua , Cao Chunxin , Sheng Yingkun , Wang Jianfeng
Published: June 2024

Sweet pepper, a globally commercialized horticultural crop, has been demonstrated to impede fat accumulation, but its mechanism remains incompletely understood. This study was designed to explore the potential mechanism of sweet pepper in reducing fat accumulation in Caenorhabditis elegans through RNA‐seq and metabolome analysis. A total of 22 metabolites were identified from sweet pepper by UHPLC‐ESI‐TOF‐MS analysis. In vivo, sweet pepper significantly inhibited α‐glucosidase activity and reduced the levels of glucose, triglycerides (TG), total cholesterol (TC), and the area stained with oil red O. Additionally, it increased body length and the number of head swings in C. elegans compared to the control group. The KEGG enrichment analysis revealed significant enrichment of the biosynthesis of unsaturated fatty acids signaling pathway among the differentially expressed genes and metabolites. Furthermore, the mRNA levels of sterol regulatory element‐binding proteins (SREBPs) ortholog SBP‐1, as well as the stearyl CoA desaturase‐1 (SCD1), including fat‐5, fat‐6, and fat‐7, were significantly decreased after treatment with sweet pepper. Collectively, sweet pepper effectively reduces fat accumulation, which is probably related to downregulating the SREBP‐SCD axis, offering new insights for future functional food development.
Inhibition of Nε‐(carboxyethyl)lysine and Nε‐(carboxymethyl)lysine formation in beef, chicken, and fish meat: A comparative study of oven frying and air frying with a marinade‐containing Micromeria fruticosa
Authors: Kılıç Altun Serap , Aydemir Mehmet Emin , Takım Kasım , Yilmaz Mustafa Abdullah
Published: June 2024

The objective of this study was to assess the impact of marinating beef, chicken, and fish with Micromeria fruticosa (M. fruticosa) on the inhibition of Nε‐(carboxyethyl)lysine (CEL) and Nε‐(carboxymethyl)lysine (CML). Furthermore, our objective was to examine how different cooking techniques, temperatures, and durations affect the creation of CEL and CML in these meat products. The study began with the characterization of M. fruticosa. Subsequently, meat samples were marinated using an M. fruticosa‐containing marinade and stored at 4 ± 1°C for 24 h. Following storage, the meats underwent cooking in an oven at 200°C for 12 min and in an air fryer at 250°C for 8 min. Subsequently, pH, color, thiobarbituric acid reactive substances (TBARS), as well as CEL and CML analyses were conducted. M. fruticosa had high levels of biological activity and bioactive content. Moreover, increasing the M. fruticosa ratio in the marinade demonstrated a reduction in TBARS, CML, and CEL formation. This study concludes that M. fruticosa can be effectively used as a marinade component for meat, inhibiting the formation of CEL and CML. In conclusion, this research underscores the significant potential of M. fruticosa in reducing the synthesis of advanced glycation end products (AGEs) during meat processing. These results not only enhance our comprehension of the complex relationship between plant extracts and meat quality but also present encouraging prospects for fostering healthier and safer cooking methods.
Identification, quantification, and antidepressant‐like evaluation of anthocyanin‐rich extracts from different dietary berries
Authors: Wang Jun , Cheng Jie , Zhu Ji‐Xiao , Xu Guang‐Hui , Huang Wei‐Feng , Yi Li‐Tao
Published: June 2024

Berries are highly valued for their rich phenolic content, particularly anthocyanins, which are known for their antioxidative properties and potential effectiveness against depression. This study identified and quantified anthocyanin profiles in blueberry, blackberry, black mulberry, and cranberry using ultra‐performance liquid chromatography–mass spectrometry (UPLC–MS), followed by in vivo evaluation of their antidepressant‐like activities. Blueberry and black mulberry showed significant levels of cyanidin‐3‐galactoside and cyanidin. Acute supplementation with these berries decreased serum corticosterone levels and increased monoamine neurotransmitters, while chronic supplementation enhanced antioxidative activity and reduced neuroinflammation in the hippocampus of mice. These findings indicate that the neurochemical, antioxidative, and anti‐inflammatory effects of blueberry and black mulberry mediate their therapeutic role against depression. Berries rich in cyanidin‐3‐galactoside and cyanidin may be valuable in developing functional foods, dietary supplements, and pharmacological formulations for mental health improvement.
Dynamics of spike transmission and suppression between principal cells and interneurons in the hippocampus and entorhinal cortex
Authors: Iwase Motosada , Diba Kamran , Pastalkova Eva , Mizuseki Kenji
Published: June 2024

Synaptic excitation and inhibition are essential for neuronal communication. However, the variables that regulate synaptic excitation and inhibition in the intact brain remain largely unknown. Here, we examined how spike transmission and suppression between principal cells (PCs) and interneurons (INTs) are modulated by activity history, brain state, cell type, and somatic distance between presynaptic and postsynaptic neurons by applying cross‐correlogram analyses to datasets recorded from the dorsal hippocampus and medial entorhinal cortex (MEC) of 11 male behaving and sleeping Long Evans rats. The strength, temporal delay, and brain‐state dependency of the spike transmission and suppression depended on the subregions/layers. The spike transmission probability of PC–INT excitatory pairs that showed short‐term depression versus short‐term facilitation was higher in CA1 and lower in CA3. Likewise, the intersomatic distance affected the proportion of PC–INT excitatory pairs that showed short‐term depression and facilitation in the opposite manner in CA1 compared with CA3. The time constant of depression was longer, while that of facilitation was shorter in MEC than in CA1 and CA3. During sharp‐wave ripples, spike transmission showed a larger gain in the MEC than in CA1 and CA3. The intersomatic distance affected the spike transmission gain during sharp‐wave ripples differently in CA1 versus CA3. A subgroup of MEC layer 3 (EC3) INTs preferentially received excitatory inputs from and inhibited MEC layer 2 (EC2) PCs. The EC2 PC–EC3 INT excitatory pairs, most of which showed short‐term depression, exhibited higher spike transmission probabilities than the EC2 PC–EC2 INT and EC3 PC–EC3 INT excitatory pairs. EC2 putative stellate cells exhibited stronger spike transmission to and received weaker spike suppression from EC3 INTs than EC2 putative pyramidal cells. This study provides detailed comparisons of monosynaptic interaction dynamics in the hippocampal–entorhinal loop, which may help to elucidate circuit operations.
Temperature distribution in stretching/shrinking fin with variable parameters
Authors: Sharma Priti , Singh Surjan , Upadhyay Subrahamanyam
Published: June 2024

In this paper, we consider a mathematical model, which has a unique mechanism of heat transfer in the stretching/shrinking straight fin with an exponential profile. The thermal conductivity, internal heat generation, and heat transfer coefficient are considered temperature‐dependent. Heat is exposed to the surroundings by convection and radiation. The governing differential equation and boundary conditions are presented in a dimensionless form. In our study, we considered variable surface emissivity, that is, a constant, and the linear function of a temperature. The convective heat transfer parameter is considered a power‐low type. The novelty of this work is the application of temperature‐dependent surface emissivity, and the problem is solved by the Legendre wavelet collocation method. A comparative analysis of the present results in the context of previous findings is presented in the form of a table for validation and found exactly the same. The impacts of distinct variables are presented in the form of figures and discussed in detail. The present analysis is focused on real‐world applications and offers valuable insights for improving the design of fins.
HIV in pregnant woman and children: Mother‐to‐child transmission of HIV in the Brazilian land border from 2010 to 2021
Authors: de Lannoy Leonor Henriette , Fuentes Anderson , Santos Patrícia C. , Coelho Ronaldo , Miranda Angélica Espinosa
Published: June 2024

Objective

The aim of the present study was to analyze the profile and trends of HIV mother‐to‐child transmission (MTCT) in the Brazilian land border strip (LBS).

Methods

This was a quantitative, ecological, and cross‐sectional study using secondary data available in the information systems of the Brazilian Ministry of Health. All cases reported in the Notifiable Diseases Information System between 2010 and 2021 were studied.

Results

Between 2010 and 2021, 275 children were born infected through MTCT, and 6076 pregnant women were living with HIV in the Brazilian LBS. HIV detection rates in pregnant women increased in all border arcs. The northern arc experienced the highest increase (19.6%), followed by the central arc (11.4%), and the southern arc (6.1%). Despite historically high detection rates, the southern arc exhibited the smallest increase. While MTCT rate decreased by 37.7% in the border area, the central arc showed no statistically significant reduction. In 2021, the average age of pregnant women was 26.2 years, 25.7% had up to 8 years of schooling, and 55.8% identified as non‐white. The majority (92.8%) received antenatal care, and 59.7% were diagnosed with HIV before prenatal care. The use of prophylactic antiretroviral therapy during prenatal care occurred in 69.6% of pregnant women, and infant prophylaxis was provided within first 24 h to 43.6% of live births.

Conclusion

The results indicate progress in reducing MTCT cases in Brazilian LBS. Disparities in HIV detection rates may be influenced by differences in testing uptake, despite mandatory testing for all babies. It is crucial to continue implementing strategies to reach these women and ensure equitable access to healthcare services for MTCT prevention.