bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enrichment for clinical trials of early AD: Combining genetic risk factors and plasma p‐tau as screening instruments
Authors: Wang Xin , Wang Xinran , Edland Steven D. , Broce Iris J. , Dale Anders M. , Banks Sarah J. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: October 2024

AbstractINTRODUCTIONIdentifying low‐cost, minimally‐invasive screening instruments for Alzheimer's disease (AD) trial enrichment will improve the efficiency of AD trials.METHODSA total of 685 cognitively normal (CN) individuals and individuals with mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were grouped according to cutoffs of genetic risk factor (G) polygenic hazard score (PHS) and tau pathology (T) plasma phosphorylated tau‐181 (p‐tau181) into four groups: G+T+, G‐T‐, G+T‐, and G‐T+. We assessed the associations between group level and longitudinal cognitive decline and AD conversion. Power analyses compared the estimated sample size required to detect differences in cognitive decline.RESULTSThe G+T+ group was associated with faster cognitive decline and higher AD risk. Clinical trials enrolling G+T+ participants would benefit from significantly reduced sample sizes compared with similar trials using only single makers as an inclusion criterion.DISCUSSIONThe combination of two low‐cost, minimally‐invasive measures—genetics and plasma biomarkers—would be a promising screening procedure for clinical trial enrollment.Highlights
Participants with unimpaired or mildly impaired cognition were grouped based on cutoffs on genetic risk factors (G: polygenic hazardous score [PHS]) and Alzheimer's pathology (T: baseline plasma phosphorylated tau‐181 [p‐tau181]).
Participants with high PHSs and plasma p‐tau181 levels (G+T+) were at risk of faster cognitive decline and AD progression.
The combination of PHS and plasma p‐tau181 could enhance clinical trial enrichment more effectively than using single biomarkers.
Reductions in the white–gray functional connectome in preclinical Alzheimer's disease and their associations with amyloid and cognition
Authors: Xu Lyuan , Zhao Yu , Choi Soyoung , Li Muwei , Schilling Kurt G. , Zu Zhongliang , Rogers Baxter P. , Ding Zhaohua , Anderson Adam W. , Landman Bennett A. , Gore John C. , Gao Yurui ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: October 2024

AbstractBACKGROUNDThe magnitudes and patterns of alterations of the white–gray matter (WM–GM) functional connectome in preclinical Alzheimer's disease (AD), and their associations with amyloid and cognition, remain unclear.METHODSWe compared regional WM–GM functional connectivity (FC) and network properties in subjects with preclinical AD (or AD dementia) and controls (total n = 344). Their associations with positron emission tomography AV45‐measured amyloid beta (Aβ) load and modified Preclinical Alzheimer Cognitive Composite (mPACC) scores were examined.RESULTSPreclinical AD subjects showed lower FC in specific WM–GM pairs and reduced segregation of control, dorsal attention, and somatomotor networks. A major portion of the reduced FC and network segregations were linked to elevated Aβ. Reduced FC of one WM–GM pair correlated with impaired mPACC. AD dementia exhibited broader reductions and stronger associations.DISCUSSIONThe WM–GM functional connectome undergoes regional and systemic dysfunctions as early as in the preclinical stage, correlating with amyloid deposition and predicting cognitive impairment.Highlights
Preclinical Alzheimer's disease (AD) subjects showed lower functional connectivity in specific white‐gray matter (WM–GM) pairs and reduced segregations of control, dorsal attention, and somatomotor networks.
A major portion of the reduced connectivity and network segregations were linked to elevated amyloid beta load.
Only one WM–GM pair's reduced connectivity was linearly correlated with impaired cognitive composite scores.
AD dementia showed more extensive reductions in connectivity, network integration, and segregation, with stronger associations with amyloid elevation and cognitive impairment.
The WM–GM functional connectome offers a distinct perspective for understanding changes in brain functional architecture throughout the AD continuum.
Repetitive transcranial magnetic stimulation elicits weight loss and improved insulin sensitivity in type 2 diabetic rats
Authors: Chen Xuanjin , Wang Ruru , Wang Xin , Liu Ming , Liu Zhipeng , Yin Tao , Li Chen 
Published: October 2024

AbstractBackgroundType 2 diabetes (T2D) accounts for the majority of diabetes incidences and remains a widespread global chronic disorder. Apart from early lifestyle changes, intervention options for T2D are mainly pharmaceutical.MethodsRepetitive transcranial magnetic stimulation (rTMS) has been approved by the FDA as a therapeutic intervention option for major depressive disorders, with further studies also indicating its role in energy metabolism and appetite. Considering its safe and non‐invasive properties, we evaluated the effects of rTMS on systemic metabolism using T2D rats.ResultsWe observed that rTMS improved glucose tolerance and insulin sensitivity in T2D rats after a 10‐day exposure. Improved systemic insulin sensitivity was maintained after a 21‐day treatment period, accompanied by modest yet significant weight loss. Circulating serum lipid levels, including those of cholesteryl ester, tryglyceride and ceramides, were also reduced following rTMS application. RNA‐seq analyses further revealed a changed expression profile of hepatic genes that are related to sterol production and fatty acid metabolism. Altered expression of hypothalamic genes that are related to appetite regulation, neural activity and ether lipid metabolism were also implicated.ConclusionIn summary, our data report a positive impact of rTMS on systemic insulin sensitivity and weight management of T2D rats. The underlying mechanisms via which rTMS regulates systemic metabolic parameters partially involve lipid utilization in the periphery as well as central regulation of energy intake and lipid metabolism.
Nahezu unendlich lange Polymere mit Ge=Ge‐Doppelbindungen
Authors: Thömmes Anna‐Lena , Büttner Thomas , Morgenstern Bernd , Janka Oliver , Kickelbick Guido , Niebuur Bart‐Jan , Kraus Tobias , Gallei Markus , Scheschkewitz David 
Published: October 2024

AbstractTrotz erheblichen Interesses an heteroatomhaltigen konjugierten Polymeren sind Beispiele mit schwereren Elementen des p‐Blocks im Konjugationspfad rar. Die kürzlich beschriebene Metathese schwererer acyclischer Diene (HADMET) ermöglichte die Synthese eines Ge=Ge‐Doppelbindungen enthaltenden Polymers, wenn auch eines unlöslichen mit begrenztem Polymerisationsgrad. Durch Einführung langer Alkylketten erhielten wir nun lösliche Vertreter mit – nach diffusionsabhängiger NMR‐Spektroskopie (DOSY) und dynamischer Lichtstreuung (DLS) – nahezu unendlichen Polymerisationsgraden. UV/Vis und NMR‐Daten bestätigen das Vorliegen von σ,π‐Konjugation entlang der Silylen‐Phenylen‐Verknüpfungen zwischen den Ge=Ge‐Einheiten. Günstige intermolekulare Dispersionswechselwirkungen führen zu leiterartigen, zylindrischen Aggregaten, wie durch Röntgendiffraktometrie (XRD), Kleinwinkel‐Röntgenstreuung (SAXS) und DLS bestätigt. AFM‐ und TEM‐Bilder abgeschiedener dünner Schichten offenbaren eine lamellare Anordnung ausgedehnter Polymerbündel.
Asymmetric Synthesis of β‐Ketoamides by Sulfonium Rearrangement
Authors: Porte Vincent , Nascimento Vinicius R. , Sirvent Ana , Tiefenbrunner Irmgard , Feng Minghao , Kaiser Daniel , Maulide Nuno 
Published: October 2024

AbstractThe synthesis of enantioenriched α‐substituted 1,3‐dicarbonyls remains a contemporary challenge in synthesis due to their tendency to undergo racemization via keto‐enol tautomerization. Herein, we report a method to access enantioenriched β‐ketoamides by a chiral sulfinimine‐mediated [3,3]‐sigmatropic sulfonium rearrangement. The transformation displays good chirality transfer, as well as excellent chemoselectivity and functional group tolerance. Diastereoselective reduction of the ketone moiety, also achievable in one‐pot fashion, affords enantioenriched β‐hydroxyamides.
Pilot study on coke oven flue gas injection desulfurization using highly active modified calcium hydroxide desulfurizer
Authors: Liu Meng , Ding Wenxi , Chang Jingyang , Wan Jun , Liu Wei , Duan Yufeng 
Published: October 2024

AbstractCalcium hydroxide injection desulfurization has attracted extensive attention because of its low cost and recyclable characteristics. The modified calcium hydroxide was prepared on the basis of the digestion of calcium lignosulfonate (wood calcium) aqueous solution with ethanol and used in the pilot test of flue gas injection desulfurization of the coke oven. The injection desulfurization experiment was carried out with calcium hydroxide modified by 50% ethanol and 20% ethanol+0.5% wood calcium. It was found that the injection desulfurization efficiency of the two modified calcium hydroxide was better than that of the unmodified calcium hydroxide under the same injection conditions. The desulfurization efficiency of 20% ethanol+0.5% calcium hydroxide modified by wood calcium can reach more than 93.7% under the condition of 2 and 5 times calcium to sulfur ratio. The XRF analysis of desulfurization product showed that the content of S element in unreturned desulfurization ash was only 1.28%, which increased to 4.46% after 5 times of return. BET results showed that the specific surface area of the returned desulfurization ash decreased from 35.115m2/g to 10.256m2/g and the pore volume decreased from 0.103cm3/g to 0.0433cm3/g.
Electrochemical synthesis, physical properties and corrosion behavior of electropolymerized polyaniline films developed on 316L stainless steel
Authors: de Carvalho Filho Carlos T. , Bastos Gustavo V. , de Vasconcelos Cláudia K. B. , Brito Pedro P. 
Published: October 2024

AbstractPolyaniline (PANI) films may be developed on metallic substrates by a variety of electrochemical techniques. In the present work, PANI films were electrodeposited on AISI 316L stainless steel substrates by cyclic voltammetry (CV), chronoamperometry (CA), and chronopotentiometry (CP) with the objective of comparing the efficacy of each method, based on the integrity of the developed films. Cyclic voltammetry and anodic polarization were used to determine optimal electrodeposition parameters for the development PANI films using the CA and CP methods. The structure and morphology of the coatings were characterized by scanning electron microscopy, energy‐dispersive x‐ray spectroscopy, Fourier‐transform infrared spectroscopy, and ultraviolet–visible spectroscopy. Among the evaluated techniques, CV led to the formation PANI films with the best homogeneity as well as the lowest number of defects, such as cracks or pores. Subsequently, the corrosion resistance of AISI 316L steels with and without PANI was compared in a physiological saline solution (0.9% NaCl). Potentiodynamic polarization tests indicated that the PANI‐coated samples exhibited lower corrosion current density values (0.012 vs. 0.018 μA/cm2) and lower passive current density values (0.04 vs. 0.06 μA/cm2) in comparison to the bare AISI 316L steel. Additionally, long‐term monitoring by electrochemical impedance spectroscopy revealed that PANI films consistently exhibited superior polarization resistance up to 32 days of exposure in the 0.9%NaCl solution (233,000 vs. 207,000 Ωcm2).
Effect of particle size on dissolution of different chemical components in Codonopsis pilosula
Authors: Huang Shuteng , Deng Hanxiu , Zhao Xue , Zhang Ruyue , Zhang Zhonglei , Li Ning , Zhang Jiayu 
Published: October 2024

AbstractCodonopsis pilosula (Franch.) Nannf. is a traditional herb for treating immunosuppression. C. pilosula boiling powder (CP‐BP) contains particles of a small size made from C. pilosula decoction pieces (CP‐DP). It is still unclear how changes in particle size during the decoction process affect the dissolution of various chemical components in C. pilosula. Herein, an ultra‐high‐performance liquid chromatography–quadrupole‐Exactive Orbitrap mass spectrometry technique was established to characterize the components of CP‐BP and CP‐DP decoctions. The contents of the components were evaluated based on the relative peak area, extract yield, and alcohol solubility rate. A total of 71 compounds were finally identified, and their content in the CP‐BP decoction was generally higher than that in the CP‐DP decoction. Alkaloids had the highest average content, whereas terpenoids were the most affected by changes in particle size. In addition, immunosuppression was used as model to investigate whether these changes have practical significance. The results of network pharmacology suggested that the phosphoinositide 3‐kinase (PI3K)–Akt pathway may be a potential pathway of C. pilosula for treating immunosuppression. The results of molecular docking indicated that compounds with large content variations have good docking affinity with key targets (epidermal growth factor receptor [EGFR], prostaglandin‐endoperoxide synthase 2 [PTGS2], and peroxisome proliferator‐activated receptor gamma [PPARG]). These results provide an important reference for further development and use of C. pilosula.
Novel Anti‐Tumor Effect of Natural Products from Aloe vera Resin and their In‐Vitro/In‐Silico Targeting Mechanism of Carbonic Anhydrase‐II and IX
Authors: Khan Majid , Ahsan Halim Sobia , Ur Rehman Najeeb , Khan Ajmal , Gibbons Simon , Csuk Rene , Uddin Jalal , Al‐Harrasi Ahmed 
Published: October 2024

AbstractHuman carbonic anhydrase (hCA) plays a vital role in the development and progression of tumors in hypoxic conditions. Herein we report the hCA‐II and hCA‐IX activities of natural products isolated from Aloe vera (L.) Burm.f., to know their potential in tumors. These isolated compounds (1–10) displayed varying degrees of inhibition against hCA‐II and hCA‐IX. All the compounds showed potent activity against hCA‐IX with IC50 values in the range of 2.9–29.1 μM. While for hCA‐II, compounds 1, 2, 5–10 exhibited IC50 in the range of 4.7–23.4 μM. The most effective hCA IX and II inhibitors, 2 and 5, were chosen for in vitro mechanism studies, revealing that they are competitive inhibitors. Furthermore, when tested for their cytotoxic effect on BJ (normal) cell line, all the compounds showed no cytotoxic behavior, while on Prostate cancer cells (PC‐3), compounds 1, 3, 5, 7, and 9 exhibited significant antiproliferative activity. Molecular docking was also conducted within the hCA IX and hCA‐II active sites to observe their binding capability. Compounds 1, 5, 7, and 9 were active against both isozymes of hCA and in the PC‐3 cell line, therefore these are the best choices for further in vivo studies.
A New Diterpenoid Alkaloid with Antimicrobial Activity from Aconitum brachypodum Diels
Authors: Shu Yan , Yao Shu , Luo Yan , Yang Hua‐Juan , Wang Jia‐Peng , Cai Le 
Published: October 2024

AbstractA new C20‐denudatine‐type diterpenoid alkaloid (DA) 11S‐aconicarnine D (1) and fifteen known DAs were isolated from the lateral roots of Aconitum brachypodum Diels. Their structures were identified on the basis of extensive spectroscopic analyses, NMR calculations and DP4+ analysis. Compounds 1 and 4 exhibited antimicrobial activity against Alternaria panax with MICs of 2.00 and 8.00 μg/mL (Nystatin, 1.00 μg/mL), respectively.
Intrathecal pain pump causing delayed acute flaccid paralysis: A case report and review of the literature
Authors: Finneran Megan , Nardone Emilio 
Published: October 2024

Key Clinical MessagePatients with intrathecal catheters for pain medication infusion should be aware of the possible complication of acute flaccid paralysis. While exceedingly rare, it should prompt immediate medical attention to rule out compressive pathology requiring intervention.
Nonlinear Frequency Response Analysis of Distributed Parameter Systems with One Spatial Coordinate
Authors: Živković Luka , Petkovska Menka 
Published: October 2024

AbstractThe objective of this paper is to investigate possible strategies for applying nonlinear frequency response (NFR) analysis based on the concept of higher‐order frequency response functions to distributed parameter systems. Three approaches are presented and compared: one based on applying the existing procedure directly to the partial differential model, and two based on approximation of the distributed parameter system with a series of lumped parameter segments. One of them treats the complete series of segments integrally, while the other treats it segment by segment, so it uses only the model of a single segment. A simple example, an isothermal plug‐flow reactor with a simple reaction mechanism, is used as a case study. Pros and cons for all three approaches are given.
The Impact of the COVID‐19 Pandemic on Mental Health and Cognitive Function in Patients With Cancer: A Systematic Literature Review
Authors: Almeida Sílvia , Frasquilho Diana , Cordeiro M. Teresa , Neto Teresa , Sousa Berta , Cardoso Fátima , Oliveira‐Maia Albino J. 
Published: October 2024

ABSTRACTBackgroundThe COVID‐19 pandeminc has had widespread impacts, but its specific effects on mental health and cognitive function in patients with cancer remain under‐explored.Recent FindingsData from the general population has suggested that mental health problems were frequent during the pandemic, namely during the initial stage of the outbreak. For patients with cancer, a systematic review and meta‐analysis of data published until January 2021 also showed elevated prevalence of depression and anxiety, and suggested that anxiety was more frequent than in health workers and healthy controls.ObjectiveThis systematic review aimed to synthesize existing evidence on the impact of the COVID‐19 pandemic on mental health and cognitive function in patients with cancer.MethodsStudies were identified through systematic search of three electronic bibliographic databases (PubMed, Web of Science, and EBSCOHOST) with adapted search strings. We included only peer‐reviewed, nonqualitative, original research papers, published between 2019 and 2022, and reporting on mental health and/or cognition outcomes during the COVID‐19 pandemic in adult patients with cancer.ResultsOf 3260 papers identified, 121 full text articles were retrieved and 71 met inclusion criteria. We found that patients with cancer reported high levels of psychological distress, anxiety and depression, as well as cognitive complaints during the pandemic. However, studies were not consistent in identifying these symptoms as effects of the pandemic specific for this population. In fact, longitudinal studies did not find consistent differences between pre‐ and post‐pandemic periods and, globally, patients with cancer did not report increased severity of these mental health symptoms in relation to the general population.ConclusionOverall, while the COVID‐19 pandemic may have raised mental health challenges for patients with cancer, the diagnosis of cancer and associated treatments seemed to remain the main source of concern for these patients.
Bioequivalence and Pharmacokinetic Evaluation of Regorafenib Tablets in Healthy Chinese Volunteers
Authors: Wang Zhaoyu , Zhang Yun , Liu Jingjing , Chen Xijing 
Published: October 2024

AbstractThis was a single‐center, randomized, open‐label, 2‐formulation, and 2‐cycle crossover trial conducted in 48 healthy Chinese volunteers, under fasting and fed conditions. The participants received oral doses of the test formulation (regorafenib) and reference formulation (40 mg) during each study period. Blood samples were collected before and up to 144 hours after the formulations were administered to determine changes in the pharmacokinetic parameters and adverse reactions, which were then used to evaluate bioequivalence and safety. The geometric mean ratios of maximum blood concentration, area under the plasma concentration‐time curve from time 0 to the last quantifiable concentration, and area under the plasma concentration‐time curve from time 0 to infinity for regorafenib were as follows: 94.7%, 91.4%, and 91.7%, respectively, under fasting conditions; and 94.6%, 97.7%, and 98.8%, respectively, under fed conditions. The 90% confidence intervals for the geometric mean ratios were within the 80%‐125% equivalence interval for both the fasting and fed tests. Ingesting high‐fat and high‐calorie foods increases exposure to regorafenib, leading to slower rates of absorption. The safety profiles of the 2 preparations were similar.
Relationship Between the Feeling of Emptiness and Suicide Reattempt: Conclusions From Cross‐Sectional and Longitudinal Analyses
Authors: Pemau Andres , Marin‐Martin Carolina , de la Torre‐Luque Alejandro , Ayad‐Ahmed Wala , Lopez‐Villatoro Jose Manuel , Fernandez‐Rodrigues Veronica , Mola Pablo , Carrasco Jose Luis , Diaz‐Marsa Marina 
Published: October 2024

ABSTRACTIntroductionThe feeling of emptiness is a complex subjective experience considered relevant in the suicidal process, acting as a risk factor for suicide ideation, attempts and even reattempts. However, empirical studies are still scarce.ObjectivesThis study has three objectives: to compare emptiness levels in healthy people and those with suicide attempts; to compare the emptiness level between people with a single suicide attempt and multiple suicide attempts at baseline; and to study emptiness as a risk factor for the appearance of new suicidal attempts after an index one.MethodologyIn the study, 382 healthy controls and 58 participants with a recent suicide attempt (in the past 15 days) participated. All completed the feeling of emptiness scale (FES). Information was also collected on sociodemographic characteristics and history of suicide attempts. First, the control sample scores were compared with those of the clinical sample. Later, the single attempt and reattempt groups (any amount greater than one attempt at baseline) were compared. Finally, the clinical sample was followed for 1 year and 3 months (through clinical records). Survival analysis was performed.ResultsThe clinical group obtained higher scores across the FES subscales, even when controlling for other relevant variables (p < 0.01). When comparing people with one versus several attempts, differences were also observed in all subscales except one, the reattempt group getting higher scores (p < 0.05). Regarding the survival analysis, the feeling of emptiness was significantly associated with the risk of reattempt (HR = 1.04; p < 0.05). All people who reattempted during follow‐up belonged to the reattempt group at baseline.ConclusionsPeople who have attempted suicide present higher emptiness scores. Furthermore, emptiness appears to significantly predict the occurrence of new attempts at follow‐up. The feeling of emptiness may be associated with the lack of vital meaning and disconnection from others, fundamental aspects of the ideation‐to‐action suicide models. Including emptiness in suicide assessments could increase clinicians' predictive ability.