bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meeting report of the fifth annual workshop on Principles and Techniques for Improving Preclinical to Clinical Translation in Alzheimer's Disease Research
Authors: Sasner Michael , Onos Kristen D. , Territo Paul R. , Sukoff Rizzo Stacey J. 
Published: February 2024

AbstractThe fifth annual workshop on Principles and Techniques for Improving Preclinical Translation of Alzheimer's Disease Research was held in May 2023 at The Jackson Laboratory in Bar Harbor, Maine, USA. The workshop was established in 2018 to address training gaps in preclinical translational studies for Alzheimer's disease (AD). In addition to providing fundamental knowledge and hands‐on skills essential for executing rigorous in vivo studies that are designed to facilitate translation, each year the workshop aims to provide insight on state‐of‐the‐field technological advances and new resources including novel animal models, publicly available datasets, novel biomarkers, and new medical imaging tracers. This innovative and comprehensive workshop continues to deliver training for the greater AD research community in order to provide investigators and trainees with the knowledge and skillsets essential for enabling improved preclinical to clinical translation and accelerate the process of advancing safe and effective therapeutic interventions for AD.Highlights
Translational research is not typically available as a course of study at academic institutions, yet there are fundamental skillsets and knowledge required to enable successful translation from preclinical experiments to clinical efficacy.
It is important that there are resources and opportunities available to researchers planning preclinical translational experiments.
Here we present proceedings from the fifth annual NIA‐sponsored workshop focused on enabling improved preclinical to clinical translation for Alzheimer's disease research that includes didactic lectures on state‐of‐the‐field approaches and hands‐on practicums for acquiring essential translational laboratory techniques.
Timing of Biomarker Changes in Sporadic Alzheimer's Disease in Estimated Years from Symptom Onset
Authors: Li Yan , Yen Daniel , Hendrix Rachel D. , Gordon Brian A. , Dlamini Sibonginkhosi , Barthélemy Nicolas R. , Aschenbrenner Andrew J. , Henson Rachel L. , Herries Elizabeth M. , Volluz Katherine , Kirmess Kristopher , Eastwood Stephanie , Meyer Matthew , Heller Maren , Jarrett Lea , McDade Eric , Holtzman David M. , Benzinger Tammie L.S. , Morris John C. , Bateman Randall J. , Xiong Chengjie , Schindler Suzanne E. 
Published: February 2024

ObjectiveA clock relating amyloid positron emission tomography (PET) to time was used to estimate the timing of biomarker changes in sporadic Alzheimer disease (AD).MethodsResearch participants were included who underwent cerebrospinal fluid (CSF) collection within 2 years of amyloid PET. The ages at amyloid onset and AD symptom onset were estimated for each individual. The timing of change for plasma, CSF, imaging, and cognitive measures was calculated by comparing restricted cubic splines of cross‐sectional data from the amyloid PET positive and negative groups.ResultsThe amyloid PET positive sub‐cohort (n = 118) had an average age of 70.4 ± 7.4 years (mean ± standard deviation) and 16% were cognitively impaired. The amyloid PET negative sub‐cohort (n = 277) included individuals with low levels of amyloid plaque burden at all scans who were cognitively unimpaired at the time of the scans. Biomarker changes were detected 15–19 years before estimated symptom onset for CSF Aβ42/Aβ40, plasma Aβ42/Aβ40, CSF pT217/T217, and amyloid PET; 12–14 years before estimated symptom onset for plasma pT217/T217, CSF neurogranin, CSF SNAP‐25, CSF sTREM2, plasma GFAP, and plasma NfL; and 7–9 years before estimated symptom onset for CSF pT205/T205, CSF YKL‐40, hippocampal volumes, and cognitive measures.InterpretationThe use of an amyloid clock enabled visualization and analysis of biomarker changes as a function of estimated years from symptom onset in sporadic AD. This study demonstrates that estimated years from symptom onset based on an amyloid clock can be used as a continuous staging measure for sporadic AD and aligns with findings in autosomal dominant AD. ANN NEUROL 2024;95:951–965
Effect of Statin Therapy on Cardiovascular Outcome in Stroke Patients with Low Baseline Low‐Density Lipoprotein Cholesterol
Authors: Kim Yong Soo , Jeong Han‐Gil , Chang Jun Young , Kim Jun Yup , Kim Beom Joon , Bae Hee‐Joon , Han Moon‐Ku 
Published: February 2024

ObjectivesTo investigate whether post‐stroke statin therapy reduces subsequent major vascular events in statin‐naïve patients with pretreatment low‐density lipoprotein cholesterol (LDL‐C) below the recommended target (≤70 mg/dL for atherosclerotic stroke and ≤100 mg/dL for non‐atherosclerotic stroke) at stroke onset.MethodsPatients from an ongoing stroke registry who had an ischemic stroke between 2011 and 2020 were screened. Statin naïve patients with baseline LDL‐C below the target were assessed. The effect of post‐stroke statin therapy on major vascular events (composite of recurrent stroke, myocardial infarction, and death) was investigated using weighted Cox regression analyses using stabilized inverse probability treatment weighting.ResultsThe baseline LDL‐C level of the 1,858 patients (mean age 67.9 ± 15.3 years, 61.4% men, 13.2% atherosclerotic stroke) included in the study was 75.7 ± 17.0 mg/dL. Statins were prescribed to 1,256 (67.7%) patients (low‐to‐moderate intensity, 23.5%; high intensity, 44.1%). Post‐stroke statin therapy was associated with a lower risk of major vascular events during 1‐year follow‐up (weighted hazard ratio 0.55, 95% confidence interval 0.42–0.71). In a subgroup of patients who were at very high risk of atherosclerotic cardiovascular disease with LDL‐C <55 mg/dL or patients who were not at very high risk of atherosclerotic cardiovascular disease with LDL‐C <70 mg/dL, post‐stroke statin therapy was also associated with a reduction in major vascular events (weighted hazard ratio 0.45, 95% confidence interval 0.29–0.70). The intensity of the most beneficial statin varied by subtype of stroke.InterpretationStatin therapy may improve vascular outcomes after ischemic stroke, even in cases of LDL‐C below the target without pre‐stroke lipid‐lowering therapy. ANN NEUROL 2024;95:876–885
The distress of one‐dimensional fertility in an African family
Authors: Nwoye Augustine 
Published: February 2024

AbstractSeveral Euro‐American approaches to couple and family therapy have been instrumental in promoting successful practice of couple and family therapy in continental Africa. This article, however, describes one instance in which an African couple's distress of one‐dimensional fertility could not be resolved by drawing solely from the Euro‐American family therapy tradition. One‐dimensional fertility is defined as a crisis that arises in conditions of sonlessness or daughterlessness in a marriage, that is, in situations where there are only male or female children born to the marriage. The use of medical intervention through the prescription of drugs often worsens rather than enhances the psychological well‐being of couples who suffer from the distress of one‐dimensional fertility. Therefore, it is considered beneficial to encourage the development and recognition of psychological literature that suggests what to be done to control such a distress without recourse to the use of medication or the complicated and sensitive procedure of in vitro fertilisation. The article suggests that the leading intervention package for attending to the challenge of couples with the distress of one‐dimensional fertility entails the exercise of inducting them into the principles and practice of the fertility awareness‐based method of family planning known as the billings ovulation method that is in harmony with the African cultural perspective.
Surface characterization and Remazol Red adsorption by asymmetric polyethersulfone membranes modified by polyelectrolyte complexes
Authors: da Silva Vale Rayane , Bezerra da Silva Vanessa , Marcio Paranhos Caio , Contiero Jonas , Knauss Daniel M. 
Published: February 2024

AbstractPolyethersulfone (PES) membranes containing 4‐fluorophenyl sulfone‐terminated poly(diallylpiperidinium hexafluorophosphate)‐sulfonated poly(ethylene terephthalate) polyelectrolyte complexes (PECs) were obtained via phase inversion using three different methods that enabled the complexation of polyelectrolytes (PELs) to occur before, after, and during membrane formation. Atomic force microscopy‐infrared spectroscopy analysis revealed varying concentrations of the polyanion depending on the preparation method and confirmed the presence of PECs in the membranes, highlighting an increase in surface roughness. Zeta potential measurements demonstrated positive surface charges for the membrane comprising PES and the polycation. The reduction in zeta potential in PEC membranes corresponded with the neutralization of positive groups by sulfonated poly(ethylene terephthalate. Scanning electron microscopy micrographs depicted surface imperfections in PEC membranes, emphasizing the influence of PECs on membrane surfaces. The water contact angle decreased, indicating increased hydrophilicity in PEC membranes. Additionally, dye adsorption results showcased significant adsorption, with the membranes absorbing at least 60% of Remazol Red from an aqueous solution. Notably, the Blend membrane outperformed others, exhibiting an exceptional adsorption rate exceeding 92%.
Construction and tribological properties of poly acrylic acid‐poly(3‐(methacryloylamino)propyl) dimethyl(3‐sulfopropyl)ammonium hydroxide hydrogel coatings embedded with SiO2 nanoparticles on Ti6Al4V substrate
Authors: Deng Yaling , Nie Lei , Xu Yu , Gao Chenhong , Wu Zhe 
Published: February 2024

AbstractThe development of highly effective bio‐lubricant coatings for arthritis treatment is extremely demanded. Herein, inspired by the efficient lubrication of articular cartilage, acrylic acid (AA) with (3‐(methacryloylamino) propyl) dimethyl (3‐sulfopropyl) ammonium hydroxide (MPDSAH) hydrogel coatings containing nanoparticles on Ti6Al4V substrate were designed and fabricated via UV grafting technology. SiO2 and SiO2 grafted with PAA polymer brushes (SiO2‐g‐PAA) were separately doped into the PAA‐PMPDSAH hydrogel. The PAA‐PMPDSAH/SiO2‐g‐PAA exhibits good tensile and compressive properties compared with PAA‐PMPDSAH/SiO2 hydrogel, with an enhancement of 183.4% in tensile modulus and 60.8% in compressive modulus. The PAA‐PMPDSAH/SiO2‐g‐PAA hydrogel coatings exhibit a low wear volume, 2.9 ± 0.16 × 106 μm3, representing a decline of 32.1% and 61.3% compared with the PAA‐PMPDSAH and PAA‐PMPDSAH/SiO2 hydrogel coatings, respectively. The antiwear performance has obviously improved. The hydrophilic PAA polymer brushes prevent the agglomeration of nanoparticles and promote homogeneously dispersion within the hydrogel. The three‐dimensional crosslinked network structure of hydrogel effectively protects the structural integrity of the polymer brushes, thereby facilitating enduring lubrication properties. This work provides a strategy for promising artificial joint lubrication in biomedical fields.
Vinyl methyl oxazolidinone as reactive diluent to overcome the solubility limitations of highly polar unsaturated polyesters
Authors: Wylezek Maciej , Kalinkin Chris , Gläser Kristin , Adermann Torben , García Romero Iván , D'Andola Giovanni , Komber Hartmut , Lorenz Reinhard , Voit Brigitte 
Published: February 2024

AbstractVinyl methyl oxazolidinone (VMOX®) is studied as a new reactive diluent (RD) for highly polar unsaturated polyesters (UPs). Molecules with special structure properties are extensively investigated as components for unsaturated polyester resins (UPRs) and thermosets, particularly for high‐temperature applications. Special diols with a cyclic structure like isosorbide and tricyclodecanedimethanol or special diols with side groups like 2‐methyl‐2‐propyl‐1,3‐propanediol and 2‐ethyl‐2‐butyl‐1,3‐propanediol can provide interesting properties. Bio‐based diols such as isosorbide and 1,3‐butanediol improve the sustainability profile. However, UPs based on such special diols have a higher polarity, limiting their solubility in styrene. This demands a RD, which provides adequate solubility and is suitable for high‐temperature applications. Therefore, our study compares the solubility of highly polar UPs based on special diols in styrene and VMOX®. UPs with different formulations, polarities, and Hansen parameters were synthesized and characterized. The solubility sphere of styrene was determined experimentally with the synthesized UPs. The influence of the special diols on the thermoset properties was investigated in dynamic mechanical analysis measurements. In conclusion, VMOX® as a RD enables full utilization of special diols properties due to the wide solubility window. Moreover, a new class of high‐temperature styrene‐free UP resin was developed.
Self‐emulsification synthesis of epoxy phosphate ester and its flame‐retardant mechanism in flexible poly(vinyl chloride)/magnesium hydroxide composites
Authors: Li Xue , Zhang Junchi , Yang Xiaoqing , Jin Yankui , Lv Zhihui , Lan Shengjie , Zhu Donghai , Dang Li 
Published: February 2024

AbstractA trade‐off dilemma exists for simultaneously improving the mechanical properties and flame resistance of flexible polyvinyl chloride (fPVC)/magnesium hydroxide (MH) composites. In this study, epoxy phosphate ester (EPE), a hydrophobic surface modifier of MH, was synthesized using a self‐emulsification method. After modification, EPE was bonded to the surface of MH (MHEPE) without altering its morphology. The results of limiting oxygen index and cone calorimetry tests indicated that fPVC/MHEPE exhibited better flame retardancy and smoke suppression effects than did fPVC/MH. The peak of the heat release rate, total heat release, peak of the smoke production rate, and total smoke production of the fPVC/MHEPE composite were 206.0 kJ m−2, 45.90 MJ m−2, 0.0729 m2 s−1, and 9.88 m2, which were 8.64%, 14.00%, 27.61%, and 9.02% lower than those of the fPVC/MH composite, respectively. For the fPVC/MHEPE composite, a compact and continuous char residue formed, which could inhibit heat and flammable volatile migration between the matrix and burning zones. In the gas phase, the dilution effect of H2O vapor reduced the concentrations of O2 and flammable volatiles. The free‐radical quenching effect of ·PO and ·PO2 also played a vital role in extinguishing flame and terminating combustion. Further, the introduction of EPE improved the tensile and impact strengths of the fPVC/MH composites because of the excellent interfacial compatibility between MHEPE and the fPVC matrix. This study provides a simple and workable solution for the trade‐off dilemma, and the remarkable flame retardancy and mechanical properties of the fPVC/MHEPE composite render it a promising cable material.
Novel quinoline derivatives with broad‐spectrum antiprotozoal activities
Authors: Hartman Carla B. , Dube Phelelisiwe S. , Legoabe Lesetja J. , Van Pelt Natascha , Matheeussen An , Caljon Guy , Beteck Richard M. 
Published: February 2024

AbstractSeveral quinoline derivatives incorporating arylnitro and aminochalcone moieties were synthesized and evaluated in vitro against a broad panel of trypanosomatid protozoan parasites responsible for sleeping sickness (Trypanosoma brucei rhodesiense), nagana (Trypanosoma brucei brucei), Chagas disease (Trypanosoma cruzi), and leishmaniasis (Leishmania infantum). Several of the compounds demonstrated significant antiprotozoal activity. Specifically, compounds 2c, 2d, and 4i displayed submicromolar activity against T. b. rhodesiense with half‐maximal effective concentration (EC50) values of 0.68, 0.8, and 0.19 µM, respectively, and with a high selectivity relative to human lung fibroblasts and mouse primary macrophages (∼100‐fold). Compounds 2d and 4i also showed considerable activity against T. b. brucei with EC50 values of 1.4 and 0.4 µM, respectively.
Ligandability assessment of the C‐terminal Rel‐homology domain of NFAT1
Authors: Böttcher Jark , Fuchs Julian E. , Mayer Moriz , Kahmann Jan , Zak Krzysztof M. , Wunberg Tobias , Woehrle Simon , Kessler Dirk 
Published: February 2024

AbstractTranscription factors are generally considered challenging, if not “undruggable”, targets but they promise new therapeutic options due to their fundamental involvement in many diseases. In this study, we aim to assess the ligandability of the C‐terminal Rel‐homology domain of nuclear factor of activated T cells 1 (NFAT1), a TF implicated in T‐cell regulation. Using a combination of experimental and computational approaches, we demonstrate that small molecule fragments can indeed bind to this protein domain. The newly identified binder is the first small molecule binder to NFAT1 validated with biophysical methods and an elucidated binding mode by X‐ray crystallography. The reported eutomer/distomer pair provides a strong basis for potential exploration of higher potency binders on the path toward degrader or glue modalities.
Quinoa as phytopharmaceutical? Urinary elimination of ecdysterone after consumption of quinoa alone and in combination with spinach
Authors: Isenmann Eduard , Yuliandra Tasha , Touvleliou Konstantina , Broekmann Matthias , de la Torre Xavier , Botrè Francesco , Diel Patrick , Parr Maria Kristina 
Published: February 2024

AbstractThe phytosteroid ecdysterone is classified as an anabolic agent and has been included on the monitoring list of the World Anti‐Doping Agency since 2020. Therefore, the consumption of food rich in ecdysterone, such as quinoa and spinach, is the focus of a lively debate. Thus, the urinary excretion of ecdysterone and its metabolites in humans was investigated following quinoa consumption alone and in combination with spinach. Eight participants (four male and four female) were included, and they ingested 368 ± 61 g cooked quinoa alone and in combination with 809 ± 115 g spinach after a washout. Post‐administration urines were analyzed by LC‐MS/MS. After intake of both preparations, ecdysterone and two metabolites were excreted in the urine. The maximum concentration of ecdysterone ranged from 0.44 to 5.5 µg/mL after quinoa and from 0.34 to 4.1 µg/mL after quinoa with spinach. The total urinary excreted amount as parent drug plus metabolites was 2.61 ± 1.1% following quinoa intake and 1.7 ± 0.9% in combination with spinach. Significant differences were found in the total urinary excreted amount of ecdysterone, 14‐deoxy‐ecdysterone, and 14‐deoxy‐poststerone. Only small portions of ecdysterone from quinoa and the combination with spinach were excreted in the urine, suggesting that both quinoa and spinach are poor sources of ecdysterone in terms of bioavailability.
SNe 2019vxm and 2020tlf: two luminous type II Supernovae with signatures of circumstellar interaction
Authors: Tsvetkov Dmitry Yu , Pavlyuk Nickolay N. , Dodin Alexandr V. , Shatsky Nickolay I. , Potanin Sergey A. , Ikonnikova Nataliya P. , Burlak Marina A. , Belinskii Aleksandr A. , Volkov Igor M. , Echeistov Vsevolod A. 
Published: February 2024

AbstractWe present optical spectroscopic and photometric observations of type II SNe 2019vxm and 2020tlf. The photometric monitoring of SN 2019vxm continued for 592 days, two spectra were collected. SN 2020tlf was observed for 163 days and we obtained one spectra. The maximum luminosity of both SNe is high: mag for SN 2019vxm and SN 2020tlf, respectively. SN 2019vxm displays typical for most of SNe IIn photometric evolution: long rise to the maximum and slow brightness decline with several changes of the decline rate. The light curve of SN 2020tlf shows it may be considered as an intermediate object between classes II‐P and II‐L. The spectral evolution of SN 2019vxm was typical for SNe IIn, while for SN 2020tlf only weak signs of circumstellar interaction were observed at maximum light.
Age at autism spectrum disorder diagnosis and its association with child and family characteristics in a tertiary care hospital in Malaysia
Authors: Singh Jasminder Kaur Amarjit , Ling Wong Hoi , Sivanesom Ranjini S. , Huay Cindy Chan Su , Lan Audrey Chong Shuk 
Published: February 2024

AbstractAutism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Despite the absence of a cure, early diagnosis and intensive early intervention can improve the outcomes. However, little is known about the median age at ASD diagnosis in Malaysia or the child/family characteristics associated with early diagnosis. Therefore, this study aimed to determine the median age at ASD diagnosis among Malaysian children presenting to the country's largest public tertiary neurodevelopmental center and to investigate the possible demographic, child, and family characteristics associated with an early age at diagnosis. Data were collected between February 2017 and February 2019 from a database maintained by the child development unit of the country's largest publicly funded tertiary hospital, containing data from an ethnically diverse population. Among Malaysian children attending the clinic, the median age at ASD diagnosis was 48 months. Early autism diagnosis (<36 months of age) was associated with increased severity of social communication and interaction impairments, coexisting intellectual impairment, children from high socioeconomic status families, and children who receive joint care from their families and a maid or babysitter. The study findings highlight the socioeconomic inequalities in the country, a lack of parental awareness of early ASD signs, and the presence of cultural influences on the age at diagnosis of ASD.
The association between pre‐diagnostic levels of psychological distress and adverse effects after radical prostatectomy
Authors: Nilsson Rasmus , Næss‐Andresen Thomas , Myklebust Tor Åge , Bernklev Tomm , Kersten Hege , Haug Erik Skaaheim 
Published: February 2024

AbstractObjectivesTo prospectively analyse the associations between pre‐diagnostic levels of anxiety and depression and patient‐reported urinary and sexual adverse effects after radical prostatectomy in a population‐based setting.Patients and MethodsIn three Norwegian county hospitals, men referred with a suspicion of prostate cancer were asked to fill out a patient‐reported outcome measurement (PROM) questionnaire prior to prostate biopsy. Those who later underwent radical prostatectomy were stratified into three distress groups according to their Hopkins Symptom Checklist 5‐score. Additional PROM questionnaires, including the EPIC‐26 to measure adverse effects, were collected at 6 and 12 months postoperatively. Multivariable mixed models were estimated and post hoc pairwise comparisons performed to explore differences in adverse effects between distress groups.ResultsA total of 416 men were included at baseline and of those, 365 (88%) returned questionnaires at 6 months and 360 (87%) at 12 months. After adjusting for confounders, men with high distress at baseline had worse urinary incontinence domain score (58.9 vs. 66.8, p = 0.028), more urinary bother (64.7 vs. 73.6, p = 0.04) and a higher risk of using incontinence pads (70.6% vs. 54.2%, p = 0.034) at 6 months than those with low distress. There was no difference in the sexual domain scores between distress groups postoperatively, but the high‐distress group expressed more sexual bother (24.9 vs. 37.5, p = 0.015) and the intermediate‐distress group had a greater probability of using sexual medications or devices (63.8% vs. 50.0%, p = 0.015) than the low‐distress group at 6 months. At 12 months scores generally improved slightly and differences between distress groups were less evident.ConclusionMen with higher levels of anxiety and depression before prostate biopsy report more urinary and sexual adverse effects after radical prostatectomy. This should be considered both in treatment decision‐making and during follow‐up after radical prostatectomy.