bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inequalities in accelerated cognitive decline: Resolving observational window bias using nested non‐linear regression
Authors: Clouston Sean A. P. , Hanes Douglas W. , Smith Dylan M. , Richmond Lauren L. , Richards Marcus , Link Bruce 
Published: July 2024

AbstractINTRODUCTIONLimited observational windows lead to conflicting results in studies examining educational differences in Alzheimer's disease and related dementias (ADRD) risk, due to observational window bias relative to onset of accelerated cognitive decline. This study tested a novel model to address observational window bias and tested for the presence and sources of disparities in accelerated cognitive declines due to ADRD.METHODSThe sample examined 167,314 cognitive assessments from 32,441 Health and Retirement Study participants. We implemented a parametric non‐linear nested longitudinal regression and reported multivariable‐adjusted nodal incidence ratios (aNIR).RESULTSUniversity degrees were associated with lower incidence (aNIR = 0.253, 95% confidence interval [CI] = [0.221 to 0.289], p < 0.001), while black participants had a higher incidence (aNIR = 1.995, [1.858 to 2.141], p < 0.001) of accelerated cognitive decline, adjusting for demographic, sociobehavioral, and medical risk factors. Sex‐stratified analyses identified diminished educational returns for women and increased incidence among minoritized women.DISCUSSIONAddressing observational window bias reveals large social inequalities in the onset of accelerated cognitive declines indicative of ADRD.Highlights
This study identifies observational window bias as a source of conflicting results among previous studies of educational achievement in Alzheimer's disease and related dementias (ADRD) disparities.
The study locates preclinical accelerated cognitive decline, which is indicative of ADRD while occurring 10+ years prior to symptom onset, as a site to study ADRD disparities that mitigates observational window bias.
A novel method, nested non‐linear regression, is developed to test for differences in the onset of accelerated cognitive decline.
Educational and racial/ethnic disparities are demonstrated in the onset of accelerated cognitive decline, as are their intersecting differences with sex/gender.
Assessing cognitive impairment and disability in older adults through the lens of whole brain white matter patterns
Authors: Roh Hyun Woong , Chauhan Nishant , Seo Sang Won , Choi Seong Hye , Kim Eun‐Joo , Cho Soo Hyun , Kim Byeong C. , Choi Jin Wook , An Young‐Sil , Park Bumhee , Lee Sun Min , Moon So Young , Nam You Jin , Hong Sunhwa , Son Sang Joon , Hong Chang Hyung , Lee Dongha 
Published: July 2024

AbstractINTRODUCTIONThis study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults.METHODSWe conducted an in‐depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter‐subject variability (WM‐ISV).RESULTSThe white matter pattern ensemble model, combining MRI and amyloid PET, demonstrated a significantly higher classification performance for cognitive impairment and disability. Participants with Alzheimer's disease (AD) exhibited higher WM‐ISV than participants with subjective cognitive decline, mild cognitive impairment, and vascular dementia. Furthermore, WM‐ISV correlated significantly with blood‐based biomarkers (such as glial fibrillary acidic protein and phosphorylated tau‐217 [p‐tau217]), and cognitive function and disability scores.DISCUSSIONOur results suggest that white matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision‐making and determining cognitive impairment and disability.Highlights
The ensemble model combined both magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) and demonstrated a significantly higher classification performance for cognitive impairment and disability.
Alzheimer's disease (AD) revealed a notably higher heterogeneity compared to that in subjective cognitive decline, mild cognitive impairment, or vascular dementia.
White matter inter‐subject variability (WM‐ISV) was significantly correlated with blood‐based biomarkers (glial fibrillary acidic protein and phosphorylated tau‐217 [p‐tau217]) and with the polygenic risk score for AD.
White matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision‐making processes and determining cognitive impairment and disability.
Efficient and Stable NIR‐II Phosphorescence of Metallophilic Molecular Oligomers for In Vivo Single‐Cell Tracking and Time‐Resolved Imaging
Authors: Shi Ben , Zhang Lu , Yan Kui , Ming Jiang , Chen Zi‐Han , Chen Ying , He Haisheng , Zhang Hongxin , Wang Lixin , Wang Shangfeng , Zhang Fan 
Published: July 2024

AbstractMolecular phosphorescence in the second near‐infrared window (NIR‐II, 1000–1700 nm) holds promise for deep‐tissue optical imaging with high contrast by overcoming background fluorescence interference. However, achieving bright and stable NIR‐II molecular phosphorescence suitable for biological applications remains a formidable challenge. Herein, we report a new series of symmetric isocyanorhodium(I) complexes that could form oligomers and exhibit bright, long‐lived (7–8 μs) phosphorescence in aqueous solution via metallophilic interaction. Ligand substituents with enhanced dispersion attraction and electron‐donating properties were explored to extend excitation/emission wavelengths and enhanced stability. Further binding the oligomers with fetal bovine serum (FBS) resulted in NIR‐II molecular phosphorescence with high quantum yields (up to 3.93 %) and long‐term stability in biological environments, enabling in vivo tracking of single‐macrophage dynamics and high‐contrast time‐resolved imaging. These results pave the way for the development of highly‐efficient NIR‐II molecular phosphorescence for biomedical applications.
Indazole to 2‐Cyanoindole Scaffold Progression for Mycobacterial Lipoamide Dehydrogenase Inhibitors Achieves Extended Target Residence Time and Improved Antibacterial Activity
Authors: Sun Shan , Ginn John , Kochanczyk Tomasz , Arango Nancy , Jiang Xiuju , Huggins David J. , Bean James , Michino Mayako , Baxt Leigh , Liverton Nigel , Meinke Peter T. , Bryk Ruslana 
Published: July 2024

AbstractTuberculosis remains a leading cause of death from a single infection worldwide. Drug resistance to existing and even new antimycobacterials calls for research into novel targets and unexplored mechanisms of action. Recently we reported on the development of tight‐binding inhibitors of Mycobacterium tuberculosis (Mtb) lipoamide dehydrogenase (Lpd), which selectively inhibit the bacterial but not the human enzyme based on a differential modality of inhibitor interaction with these targets. Here we report on the striking improvement in inhibitor residence time on the Mtb enzyme associated with scaffold progression from an indazole to 2‐cyanoindole. Cryo‐EM of Lpd with the bound 2‐cyanoindole inhibitor 19 confirmed displacement of the buried water molecule deep in the binding channel with a cyano group. The ensuing hours‐long improvement in on‐target residence time is associated with enhanced antibacterial activity in axenic culture and in primary mouse macrophages. Resistance to 2‐cyanoindole inhibitors involves mutations within the inhibitor binding site that have little effect on inhibitor affinity but change the modality of inhibitor‐target interaction, resulting in fast dissociation from Lpd. These findings underscore that on‐target residence time is a major determinant of antibacterial activity and in vivo efficacy.
Photoinduced Electron Donor Acceptor Complex‐Enabled α‐C(sp3)−H Alkenylation of Amines
Authors: Lu Jianzhong , Yuan Kaiyao , Zheng Jialian , Zhang He , Chen Shuting , Ma Ji , Liu Xinyu , Tu Binbin , Zhang Guozhu , Guo Rui 
Published: July 2024

AbstractAllylic amines are prevalent and vital structural components present in many bioactive compounds and natural products. Additionally, they serve as valuable intermediates and building blocks, with wide‐ranging applications in organic synthesis. However, direct α‐C(sp3)−H alkenylation of feedstock amines, particularly for the preparation of α‐alkenylated cyclic amines, has posed a longstanding challenge. Herein, we present a general, mild, operationally simple, and transition‐metal‐free α‐alkenylation of various readily available amines with alkenylborate esters in excellent E/Z ‐ and diastereoselectivities. This method features good compatibility with water and oxygen, broad substrate scope, and excellent functional group tolerance, thereby enabling the late‐stage modification of various complex molecules. Mechanistic studies suggest that the formation of a photoactive electron donor‐acceptor complex between 2‐iodobenzamide and the tetraalkoxyborate anion, which subsequently undergoes photoinduced single electron transfer and intramolecular 1,5‐hydrogen atom transfer to generate the crucial α‐amino radicals, is the key to success of this chemistry.
Short‐cut polyisophthaloyl metaphenylene diamine fiber reinforced polyimide aerogel composites for improving thermal insulation and mechanical performance
Authors: Liu Chen , Wang Boxue , Zhang Jin , Chen Mingpeng , Liu Qingju 
Published: July 2024

AbstractPolyimide aerogels are often constrained by the poor mechanical performance when used as thermal insulation. In addition, there is requirement for flame retardant performance in the practical use. In this paper, a fiber‐reinforced polyimide aerogel material was prepared by compounding polyisophthaloyl metaphenylene diamine fibers with the aerogel, which present good thermal insulation and excellent mechanical properties, flame retardancy, thermal stability, and certain hydrophobicity, as well as being very lightweight. The compressive strength of the polyimide aerogel was increased from 0.34 to 0.58 MPa by using the fibers as the reinforcing phase; meanwhile, the flame‐retardant property was improved, and the limit oxygen index was increased from 33.8 to 36.5. The composite aerogel material has good potential for application in the fields of thermal insulation, building insulation, aerospace, etc.
Facile construction of recyclable heat‐resistant polymers via alkaline‐induced cation‐π cross‐linking
Authors: Yuan Rui , Huang Ying , Ma Tengning , Kang Ming , Yang Li , Liang Qianqian , Chang Guanjun 
Published: July 2024

AbstractThe cation‐π cross‐linked heat‐resistant K‐poly(N‐aryleneindole sulphone) PINSU film, which has a high glass transition temperature (Tg = 268°C) and a decomposition temperature (Td = 547°C), was prepared by soaking PINSU film in alkaline aqueous solutions. Compared with the linear polymer PINSU, the Tg and Td of the K‐PINSU were significantly enhanced. The dynamic cation‐π cross‐linking can be reversibly removed and reconstructed driven by external stimulations in the polymer network, which endows the cross‐linked K‐PINSU with cyclable behavior and excellent mechanical stability. In addition, we have successfully demonstrated that the Tg of the K‐PINSU can be nondestructively detected by monitoring the changes in fluorescence intensity.
Validating motor delays across the developmental coordination disorder‐questionnaire and the Vineland adaptive behavior scales (VABS) in children with autism spectrum disorderASD: A SPARK dataset analysis
Authors: Bhat A. N. 
Published: July 2024

AbstractMotor delays in children with autism spectrum disorder (ASD) are being increasingly recognized using a brief screening tool, called the Developmental Coordination Disorder‐Questionnaire (DCD‐Q). Further validation of these motor delays using a more robust normed, developmental measure is clearly warranted. In this analysis, a nationally representative sample from the SPARK study was used wherein parents completed the DCD‐Q and a more widely used developmental/adaptive functioning measure, called the Vineland Adaptive Behavior Scales (VABS); which comprises of various developmental domains including the motor domain (N = 2,644 completed the DCD‐Q and VABS). Eighty two percent children with ASD had a motor delay based on their DCD‐Q scores whereas 77% children with ASD had a motor delay based on their VABS motor domain scores. Approximately 70% children with ASD had concurrent motor delay on the DCD‐Q and the VABS (i.e., positive predictive value of DCD‐Q). Furthermore, there was 81.2% accuracy in reporting a risk/no risk of motor delay across both measures. Overall, these statistics align with the recent reports on proportions of children with ASD having motor delays. Parents of ~70% children with ASD are reporting motor delays that are corroborated across two different motor measures. This not only validates the motor delays reported based on the DCD‐Q but also indicates the need for concurrent motor screening using both DCD‐Q and VABS for better detection of motor delays in children with ASD. Only 10%–32% of the current SPARK sample received any physical or recreational therapies. This mismatch between presence of motor delays and the lack of access to motor services highlights the need for more motor intervention referrals for children with ASD.
Novel calibration design improves knowledge transfer across products for the characterization of pharmaceutical bioprocesses
Authors: Helleckes Laura M. , Wirnsperger Claus , Polak Jakub , Guillén‐Gosálbez Gonzalo , Butté Alessandro , von Stosch Moritz 
Published: July 2024

AbstractModern machine learning has the potential to fundamentally change the way bioprocesses are developed. In particular, horizontal knowledge transfer methods, which seek to exploit data from historical processes to facilitate process development for a new product, provide an opportunity to rethink current workflows. In this work, we first assess the potential of two knowledge transfer approaches, meta learning and one‐hot encoding, in combination with Gaussian process (GP) models. We compare their performance with GPs trained only on data of the new process, that is, local models. Using simulated mammalian cell culture data, we observe that both knowledge transfer approaches exhibit test set errors that are approximately halved compared to those of the local models when two, four, or eight experiments of the new product are used for training. Subsequently, we address the question whether experiments for a new product could be designed more effectively by exploiting existing knowledge. In particular, we suggest to specifically design a few runs for the novel product to calibrate knowledge transfer models, a task that we coin calibration design. We propose a customized objective function to identify a set of calibration design runs, which exploits differences in the process evolution of historical products. In two simulated case studies, we observed that training with calibration designs yields similar test set errors compared to common design of experiments approaches. However, the former requires approximately four times fewer experiments. Overall, the results suggest that process development could be significantly streamlined when systematically carrying knowledge from one product to the next.
Trends in primary care blood tests prior to lung and colorectal cancer diagnosis—A retrospective cohort study using linked Australian data
Authors: Rafiq Meena , Drosdowsky Allison , Solomon Ben , Alexander Marliese , Gibbs Peter , Wright Gavin , Yeung Justin M. , Lyratzopoulos Georgios , Emery Jon 
Published: July 2024

AbstractIntroductionAbnormal results in common blood tests may occur several months before lung cancer (LC) and colorectal cancer (CRC) diagnosis. Identifying early blood markers of cancer and distinct blood test signatures could support earlier diagnosis in general practice.MethodsUsing linked Australian primary care and hospital cancer registry data, we conducted a cohort study of 855 LC and 399 CRC patients diagnosed between 2001 and 2021. Requests and results from general practice blood tests (six acute phase reactants [APR] and six red blood cell indices [RBCI]) were examined in the 2 years before cancer diagnosis. Poisson regression models were used to estimate monthly incidence rates and examine pre‐diagnostic trends in blood test use and abnormal results prior to cancer diagnosis, comparing patterns in LC and CRC patients.ResultsGeneral practice blood test requests increase from 7 months before CRC and 6 months before LC diagnosis. Abnormalities in many APR and RBCI tests increase several months before cancer diagnosis, often occur prior to or in the absence of anaemia (in 51% of CRC and 81% of LC patients with abnormalities), and are different in LC and CRC patients.ConclusionsThis study demonstrates an increase in diagnostic activity in Australian general practice several months before LC and CRC diagnosis, indicating potential opportunities for earlier diagnosis. It identifies blood test abnormalities and distinct signatures that are early markers of LC and CRC. If combined with other pre‐diagnostic information, these blood tests have potential to support GPs in prioritising patients for cancer investigation of different sites to expedite diagnosis.
Retinoic acid reduces kidney injury by regulating oxidative stress, NRF‐2, and apoptosis in hyperoxic mice
Authors: Kayalar Ozgecan , Bayrak Bertan Boran , Yildirim Merve , Yanardag Refiye , Oztay Fusun 
Published: July 2024

AbstractNuclear factor‐erythroid‐2‐related factor‐2 (NRF‐2) is a cellular resistance protein to oxidants. We investigated the effect of exogenous all‐trans retinoic acid (ATRA) on the antioxidant system and NRF‐2 in mice kidneys under hyperoxia‐induced oxidative stress. Mice were divided into four groups. Daily, two groups were given either peanut‐oil/dimethyl sulfoxide (PoDMSO) mixture or 50 mg/kg ATRA. Oxidative stress was induced by hyperoxia in the remaining groups. They were treated with PoDMSO or ATRA as described above, following hyperoxia (100% oxygen) for 72 h. NRF‐2 and active‐caspase‐3 levels, lipid peroxidation (LPO), activities of antioxidant enzymes, xanthine oxidase (XO), paraoxonase1 (PON1), lactate dehydrogenase (LDH), tissue factor (TF), and prolidase were assayed in kidneys. Hyperoxia causes kidney damage induced by oxidative stress and apoptosis. Increased LPO, LDH, TF, and XO activities and decreased PON1 and prolidase activities contributed to kidney damage in hyperoxic mice. After hyperoxia, increases in the activities of antioxidant enzymes and NRF‐2 level could not prevent this damage. ATRA attenuated damage via its oxidative stress‐lowering effect. The decreased LDH and TF activities increased PON1 and prolidase activities, and normalized antioxidant statuses are indicators of the positive effects of ATRA. We recommend that ATRA can be used as a renoprotective agent against oxidative stress induced‐kidney damage.
Complex Formation and Hydrolytic Processes of Protected Peptides Containing the −SXH− Motif in the Presence of Nickel(II) Ion
Authors: Sándor Balázs , Grenács Ágnes , Nagy Lajos , Hollóczki Oldamur , Várnagy Katalin 
Published: July 2024

AbstractInteractions between metal ions and proteins are considered reversible, such as the coordination of a metal ion to a protein or enzyme, but irreversible processes like the oxidative reactions, aggregation or hydrolytic processes may occur. In the presence of Ni(II)‐ions selective hydrolysis of the peptides containing the −SXH− or −TXH− motif was observed. Since the side chain of histidine serves as the metal ion binding site for many native proteins, and very often histidine is present in a −SXH− or −TXH− sequence, to study the complex formation and hydrolytic processes in presence of nickel(II) ion four peptides were synthesised: Ac‐SKHM‐NH2, A3SSH‐NH2, A4SSH‐NH2, AAAϵKSH‐NH2. The Ni(II)‐induced hydrolysis of Ac‐SKHM‐NH2 peptide occurs rapidly in alkaline medium already at room temperature. In two peptides containing −SSH− sequence on the C‐termini, the N‐terminal part is the major binding site for the nickel(II) ion, but the formation of dinuclear complexes was also observed. In the [Ni2LH−6]2− complex of hexapeptide, the coordination sphere of the metal ions is saturated with deprotonated Ser‐O−, which does not result in hydrolysis of the peptide. For A4SSH‐NH2, both Ni(II) ions fulfill the conditions for hydrolysis, which was confirmed by HPLC analyses at pH ≈8.2 and 25 °C.
Left main coronary artery aneurysm occlusion presenting as myocardial infarction with cardiogenic shock: Patient saved by securing left anterior descending artery at cost the of other vessels
Authors: Chandra Sharad , Choudhary Rajeev Krishna , Shukla Ayush , Chaudhary Gaurav , Mahalawat Somya , Nagar Saurabh , Sharma Akhil 
Published: July 2024

Key Clinical MessageCoronary artery aneurysms and ST‐segment elevation myocardial infarction are rare in clinical practice, presenting a management challenge. To the best of our knowledge, this case appears to be the first successful percutaneous treatment of a completely obstructed aneurysmal left main coronary artery.
Diagnostic and therapy of an early‐stage primary leiomyosarcoma of the sigmoid colon: A case report
Authors: Fickenscher M. , Gvozdenovic N. , Ponsel O. 
Published: July 2024

Key Clinical MessagePrimary leiomyosarcoma of the colon is a very rare tumor entity. Because of unspecific findings, diagnostic can be challenging. Most cases are diagnosed in advanced stages with poor overall survival. Unclear histological findings of smooth muscle cell tissue in colon biopsies together with a tumor of the colon wall in computed tomography (CT) imaging should lead to the differential diagnosis of primary colonic leiomyosarcoma and further diagnostic procedures.AbstractPrimary colonic leiomyosarcoma is an extremely rare tumor entity arising from smooth muscle cells in the colon wall. Only 0.1% of all colorectal malignancies are leiomyosarcomas. Most patients are diagnosed in advanced disease stages. The overall survival rates are low, and recurrence rates are high. Only few data regarding the outcome in localized early disease stages are available. We report the case of an early‐stage primary leiomyosarcoma of the sigmoid colon treated with surgical resection. We present the case of a 53‐year‐old male patient who underwent a colonoscopy due to intermittent rectal bleeding. Colonoscopy revealed an intraluminal polypoid growing tumor in the sigmoid colon. A biopsy was performed with inconclusive histological results. A CT scan revealed a process in the sigmoid colon with wall thickening; there was no evidence of metastatic lesions. After laparoscopic oncological resection of the sigmoid colon, histological examination surprisingly revealed a localized high‐grade leiomyosarcoma. Primary leiomyosarcoma of the colon is a rare tumor entity and diagnostic can be challenging. Only a few patients with colonic leiomyosarcoma diagnosed in localized early disease stages and treated with complete surgical resection have been reported in the literature. These patients seem to have a better prognosis with longer overall survival. Because of unspecific diagnostic findings and the lack of symptoms in early disease stages, interdisciplinary collaborations between gastroenterologists, radiologists, pathologists, and surgeons are crucial for early diagnosis and treatment.