bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal characterization of white matter degeneration in early stages of AD
Authors: Kim Jeongchul , Jung Youngkyoo , Barcus Richard A. , Lipford Megan E. , Hughes Tim M. , Lockhart Samuel N. , Baker Laura D , Craft Suzanne , Whitlow Christopher T.
Published: June 2023

Background

White matter (WM) degeneration in older adults is often characterized unimodally by diffusion tensor imaging (DTI), T1w and T2‐FLAIR MRI. However, approaches integrating multimodal MRI information will be necessary for better understanding WM degeneration in early stages of AD.

Method

This study characterizes the longitudinal changes of WM structure among 66 participants with marked baseline white matter hyperintensity volume (WMHv > 2000 mm3). 42 cognitively normal [CN, 72±7.2y, F = 25] and 24 mild cognitive impairment [MCI, 74±5.7y, F = 14]) adults underwent longitudinal MRI (scan interval: 2.8±0.85 years) within the Wake Forest AD Research Center. DTI metrics were estimated using FMRIB’s Diffusion Toolbox, voxel‐wise volumetric changes of WM (Jacobian Determinant [JD]) were estimated from fractional anisotropy (FA) maps using SPM CAT12, and WMHv were quantified using SPM’s Lesion Segmentation Toolbox. We segmented WM into WMH and normal‐appearing WM (NAWM) to characterize different degeneration patterns by integrating multimodal MRI information. We performed a linear regression analysis of %WMHv change with cognitive status, scan interval, and baseline WMH volume as covariates.

Result

Decreased FA and increased mean diffusivity (MD) were observed in WMH regions compared with NAWM. Within WMH, interestingly, volume and FA increased, while MD decreased (p <0.001) during the longitudinal follow‐up (Figs. 1 and 2). Baseline WMHv was not significantly associated with cognitive status, but trended toward higher WMHv in MCI compared to CN (p = 0.07). Adjusted for baseline WMHv, cognitive status was associated with WMHv change (p = 0.036, MCI faster than CN, Fig. 3). While FA (p = 0.99) and MD (p = 0.16) did not change in the NAWM, volumetric change rate (JD) indicated volumetric contraction (p<0.001, Figs. 4 and 5). WMH progresses with time in older adults at risk of AD dementia by occupying neighboring NAWM regions, resulting in relative increases in FA and decreases in MD.

Conclusion

In NAWM, WM degeneration can be better characterized by volumetric contraction than white matter microstructural integrity. This observation could implicate that secondary or peripheral WM fibers may reveal more vulnerable tracts in early stages of AD. Further investigation incorporating imaging makers of blood perfusion and metabolism could better explain structural mechanisms of WM degeneration.
Understanding paradoxical lucidity: Family caregiver interpretations of lucid episodes among people with late‐stage Alzheimer’s disease and related dementias
Authors: Griffin Joan M. , Finnie Dawn , Kim Kyungmin , Lapid Maria I. , Biggar Virginia S. , Frangiosa Theresa , Gaugler Joseph
Published: June 2023

Background

Paradoxical lucidity is characterized by spontaneous mental clarity with verbal or non‐verbal communication or behavior among people with AD who had previously been thought to lack the cognitive capacity to do so. With a paucity of data available, family caregivers (FCGs) provide critical perspectives on characteristics of these episodes of lucidity (EL).

Method

Twenty‐four FCGs who witnessed at least one EL were interviewed about the experience. Qualitative data were transcribed, double coded, and analyzed to help characterize ELs.

Result

FCGs described ELs as indelible moments, possibly triggered by music, food, holidays, or impending death. The spontaneity of the EL, its duration, the connectedness with FCGs, and coherence of communication varied. Instead of seeing them as cognitive fluctuations, FCGs often assigned metaphysical meaning to ELs.

Conclusion

FCG descriptions of ELs had few common patterns, suggestions they are heterogenous. Their impact on FCGs, however, was enduring.
Decreased functional integration in higher‐order association areas in individuals with autosomal‐dominant Alzheimer’s disease: Findings from the Colombia‐Boston (COLBOS) biomarker study
Authors: Castrillon Gabriel , Bustamante Catalina , Guzman‐Velez Edmarie , Langella Stephanie , Aduen Paula , Vila‐Castelar Clara , Fox‐Fuller Joshua T , Oliveira Gabriel , Baena Ana Y. , Lopera Francisco , Quiroz Yakeel T.
Published: June 2023

Background

The disruption of brain functional connections has been linked to cognitive impairment in Alzheimer’s disease. The functional architecture of the brain can be modeled using graph theory, which provides metrics to describe both local and global network properties. Autosomal dominant Alzheimer’s disease (ADAD) provides a unique opportunity to study brain changes in preclinical AD since carriers of ADAD mutations are destined to develop dementia at young age and have a well‐characterized disease trajectory. Here, we applied a graph theory approach to examine the functional network topology in Presenilin‐1 (PSEN1) E280A carriers and non‐carriers.

Methods

A total of 43 cognitively‐unimpaired individuals (18 PSEN1 carriers, 25 non‐carriers; mean age = 36.6±5.2) from the Colombia‐Boston biomarker study were included. Participants underwent resting‐state fMRI in a 3T scanner, and a comprehensive multi‐domain neuropsychological battery. fMRI data were preprocessed using C‐PAC. Global functional connectivity (FC) was derived from the nodal strength of the Pearson correlation matrix between time‐series of 400 ROIs [Shaeffer‐2016] within 6 different functional networks [Yeo‐2011]. The strength of within‐ (z) and between‐network (h) functional integration was derived from a consensus modularity analysis [Dwyer‐2014]. Differences in cognitive variables were evaluated using Mann‐Whitney tests. Differences in FC were assessed using permutation methods: global FC using FSL‐randomize and integration parameters were based on a consensus analysis applied to random controlled matrices. Both methods were repeated 1000 times, with a p<0.05 significance threshold.

Results

There were no group differences in cognitive variables. Compared to non‐carriers, carriers exhibited decreased local FC in higher‐order association areas, and increased connectivity in somatosensory areas. There were no group differences in the within‐network integration. Carriers showed decreased between‐network integration, especially in higher‐order association networks, mainly the default mode network (Fig.1).

Conclusions

Findings support the hypothesis that alterations of functional network topology are evident in preclinical ADAD, primarily in the higher‐order cognitive networks. Early identification of abnormalities within these networks may be useful in understanding how FC changes may lead to subsequent cognitive decline in individuals at increased risk for AD. Future work with larger samples should investigate the relationships between FC changes and the neurobiological factors underlying AD.
Chromosome 19 polygenic risk scores defined by deep learning model predict the rate of Alzheimer’ disease progression
Authors: Bae Jinhyeong , Sanjay Apoorva Bharthur , Nho Kwangsik , Saykin Andrew J. , Penchev Valentin , Apostolova Liana G.
Published: June 2023

Background

Genetic variants invariably play a crucial role in rate of disease progression. The effects of Alzheimer’s disease (AD) genetic risk factors on disease progression remains poorly understood. We developed a novel deep learning framework that could identify a personalized polygenic risk score (PRS) at the individual chromosomal level. We further used the individual’s PRS to predict the rate of cognitive decline and cerebrospinal fluid (CSF) biomarker changes.

Method

We applied a novel deep learning model to the 266,161 SNP chromosome 19 data of 313 AD and 457 cognitively unimpaired (CU) ADNI patients. The top 35 AD‐determining SNPs were determined and validated in an external dataset. Next, we used multiple regression to analyze the contribution of each combination of 3/35 SNPs to predict the rate of CSF accumulation (amyloid beta (Aβ), tau, phosphorylated tau (pTau), Aβ /tau, and Aβ/pTau) and the rate of cognitive decline in the memory, language, executive functioning, and visuospatial domains while controlling for age, sex, and education.

Result

All regression models were significant at the 0.05 level. The R‐squared adjusted values for each of the CSF models listed above were 0.917, 0.845, 0.902, 0.939, and 0.878, respectively. The majority of SNPs selected for the CSF regression models mapped to APOC1, APOC2, and TOMM40. The R‐squared adjusted values for the cognitive models were 0.188, 0.215, 0.436, and 0.266, respectively. The selected SNPs mapped to APOC1, TOMM40, VRK3, and NECTIN2. Given the less robust predictive power for cognitive change over time we increased the search to the top 150 AD SNPs. This produced R‐squared adjusted values of 0.426, 0.437, 0.607, and 0.557, respectively. The selected SNPS mapped to TOMM40, APOC1P1, ERCC1, IGSF23, ZNF556, CKM, APOC2, ZNF473, and CEACAM22P.

Conclusion

Our deep learning model PRS can successfully predict the AD cognitive and biomarker changes over time. Our model’s capability in deciphering the impact of SNPs on AD development could prove critical for early presymptomatic risk assessment and personalized therapeutic strategy approaches.
School‐based adult social support in segregated schools and late‐life cognitive function in the study of healthy aging in african americans (STAR)
Authors: Gutierrez Sirena , Whitmer Rachel A. , Soh Yenee , Peterson Rachel L. , George Kristen M , Lor Yi , Barnes Lisa L. , Mayeda Elizabeth Rose , Glymour M. Maria , Gilsanz Paola
Published: June 2023

Background

It is unclear how school segregation, a form of structural racism, affects late‐life cognition. Though segregated schools were often under‐resourced, they likely shielded Black students from interpersonal racism present at integrated schools. Social support may mediate and/or modify the relationship between school segregation and cognition.

Method

467 STAR participants aged 50+ reported if they attended a segregated school in 1st and 6th grade and received grade‐specific school‐based social support (feeling cared for by an adult at school). Baseline executive function (EF), semantic memory (SM), and verbal episodic memory (VEM) were measured using the Spanish and English Neuropsychological Assessment Scales. For each grade, linear regression models evaluated the association of segregated school attendance with each cognitive domain, sequentially adjusting for demographics, school‐based social support, and education (in pooled models). Effect modification by school‐based social support was examined through stratified models and interaction terms.

Result

The mean age was 68.2 (Table 1). Participants attending a segregated school in either grade were more likely to report school‐based social support than those in integrated schools (both p‐values<0.05; Figure 1). For each grade, attending a segregated vs integrated school was not associated with EF or VEM but was associated with lower SM (β(95% CI): ‐0.28(‐0.48, ‐0.08); Figure 2); results were similar when adjusting for social support. For each grade, effect estimates of attending a segregated school on SM and EF were smaller among those with social support than those without, though differences were not statistically significant (interaction p‐values>0.05;Table 2). In first grade, attending a segregated school was associated with SM among those without social support (β(95% CI): ‐0.40(‐0.78, ‐0.02)) but not among those with social support (β(95% CI): ‐0.10(‐0.36, 0.16)). The effect of attending a segregated school on VEM was not lower among those with social support in 1st or 6th grade than their counterparts without it. Stratified results were similar when adjusting for education.

Conclusion

Having attended a segregated school may have both harmful and protective effects on late‐life cognition. Our findings suggest that potential harmful effects of having attended segregated schools may be diminished by the increased likelihood of school‐based social support.
Reduced temporal lobe cerebral blood flow is associated with regional white matter damage among apolipoprotein E ε4 carriers
Authors: Moore Elizabeth E. , Khan Omair A. , Shashikumar Niranjana , Pechman Kimberly R. , Liu Dandan , Houston Michelle L , Archer Derek B , Gifford Katherine A. , Landman Bennett A. , Hohman Timothy J. , Jefferson Angela L.
Published: June 2023

Background

Reduced cerebral blood flow (CBF) is a risk factor for white matter damage. Apolipoprotein E (APOE) e4, a genetic risk factor for Alzheimer’s disease and vascular health modifier, is associated with lower CBF. However, it remains unknown if lower CBF is associated with more severe white matter damage among APOE‐e4 carriers. We examine whether associations among regional CBF, cerebrovascular reactivity (CVR), and white matter integrity are modified by APOE‐e4 status in older adults.

Method

Vanderbilt Memory and Aging Project participants (n = 313, 73±7 years) underwent 3T brain MRI. Resting grey matter CBF and CVR (CBF response to hypercapnic stimulus, ΔCBF/100*ΔCO2) were quantified in regions of interest from pseudo‐continuous arterial spin labeling (ASL). Fractional anisotropy (FA) was quantified from diffusion tensor imaging in tracts of interest derived from tractography templates. Linear regressions related regional CBF and CVR to tract‐specific FA, adjusting for demographic and vascular variables, regional tissue volume, cognitive status, and APOE‐e4 status. Follow‐up models tested an APOE‐ε4 status x ASL variable interaction term.

Result

In main models, lower temporal lobe CBF was associated with lower FA in the occipital lobe, suggesting compromised white matter integrity (p = 0.02). Lower CBF and higher CVR in the occipital lobe were associated with compromised lower FA in all lobes (all p‐values<0.04). Temporal lobe CBF and CVR interacted with APOE‐e4 status, such that lower temporal lobe CBF related to lower FA in the frontal lobe (p = 0.01) and higher temporal lobe CVR related to lower FA in the frontal (p = 0.001) and temporal (p = 0.007) lobes among APOE‐e4 carriers only. Frontal lobe CVR interacted with APOE‐e4 status, such that higher CVR related to lower FA in the frontal (p<0.001) and temporal lobes (p = 0.008) in APOE‐e4 carriers only.

Conclusion

Among older adults, APOE‐e4 modifies associations between cerebral hemodynamics and white matter integrity, such that reduced CBF and greater CVR in the temporal lobe are associated with greater white matter damage in APOE‐e4 carriers. APOE‐e4 carriers may be more susceptible to changes in temporal lobe hemodynamics, and vascular changes in the temporal lobe may have a stronger impact on brain health outcomes for carriers compared to non‐carriers.
MicroRNA in Alzheimer’s Disease: Results of interaction analysis
Authors: Yashin Anatoliy I , Wu Deqing , Arbeev Konstantin , Bagley Olivia , Duan Matt , Ukraintseva Svetlana
Published: June 2023

Background

MiRNA are multifunctional molecules involved in regulating posttranscriptional expression of genes. Several studies showed that miR‐107 influences expression of the BACE1 gene in the process of Aβ production. Extracellular accumulation of Aβ is well‐known hallmark of Alzheimer’s disease (AD). The product NLRP3 gene is involved in inflammasome that induces neuroinflammation a pathological process accompanying AD. The role of miR‐107 in regulation of NRLP3 is unknown.

Method

We used logistic regression model with the interaction term to test the hypothesis that interaction of SNPs from miR‐107 with SNPs from the NLRP3 gene is associated with AD. For this we used data on genotyped individuals collected in Framingham Health Study (FHS). The Cardiovascular Health Study (CHS) was used to replicate the research findings. Linkage Disequilibrium test and clumping procedure were used to reduce the number of tests and make Bonferroni correction less conservative.

Result

In the analysis of FHS data we found that the association of the rs2926616 SNP from the miR‐107 miRNA with the rs10754557 SNP from the NLRP3 gene is positive and statistically significant. The effect size β = 0.356, p‐value 6.71E‐03. This value is smaller than the p‐value threshold calculated in accordance with Bonferroni correction 7.14E‐03. This result is replicated in the analysis of CHS data with β = 0.289, and p‐value 4.76E‐02. Using FHS data we also tested the role of interaction of SNPs from the miR‐107 with SNPs from the TLR2 gene in AD and found a pair of SNPs whose interaction has statistically significant association with AD. This finding was replicated in the analysis of the CHS data where an interaction of a pair of SNPs also showed significant association with AD. Detected SNPs from this pair were in linkage disequilibrium with the pair SNPs from the CHS data.

Conclusion

The results of these analyses indicate that one miRNA may influence several components of AD pathological development. This property may have important implications for developing efficient medications against AD. More studies are needed to evaluate miRNA involvement in different pathways of AD regulation, as well as in identifying factors capable in affecting such miRNA.
Sex differences in cerebrospinal fluid testing for Alzheimer disease biomarkers: A seven‐year retrospective analysis of real‐world experience in a dementia clinic
Authors: Krivanek Taylor , Gale Seth A
Published: June 2023

Background

At the Brigham and Women’s Hospital Alzheimer Center, approximately 1100 patients are seen annually for diagnostic evaluation. Testing cerebrospinal fluid (CSF) via lumbar puncture (LP) for biomarkers of Alzheimer disease (AD) is one of the easiest and most definitive ways to make an AD diagnosis.

Method

A retrospective review of records at the Alzheimer Center was conducted for patients who underwent LP for CSF AD biomarkers from 2010 to 2017. During this period, 166 patients had their CSF tested. Demographic information was available for 163 patients, and test results were available for 155 patients.

Result

LPs for CSF biomarkers were more likely to be performed on men than women. 56% percent of patients tested were men, though men made up only about 47% of all patients seen at our center over this period. There was no significant difference in average age between men and women who were tested. Compared to women, tested men were more than twice as likely to identify as Hispanic or Latino and over four times as likely to identify as Black. Additionally, 41% of women received test results consistent with AD, compared to 30% of men. Between sexes, there was no significant difference in documented rationale for obtaining the test (i.e., exploratory testing vs. differentiating between neurodegenerative dementias or confirming a diagnosis).

Conclusion

Prevalence rates suggest that two‐thirds of individuals with AD in the United States are women. Thus, it is unsurprising that LP results for women at our center were more likely to indicate AD. However, since most individuals with AD or all‐cause dementia and patients treated at our center are women, the higher rate of men receiving the test was unexpected. It is unclear what is driving more men than women to be tested at our center and why women of color are much less likely to be tested. More research is needed to understand the factors behind these trends and to ensure an equitable approach to diagnostic testing for dementia.
Association of acoustic perturbation measures with dementia status: A Framingham Heart Study
Authors: Xue Chonghua , Karjadi Cody , Miller Matthew I. , Cordella Claire , Au Rhoda , Kolachalama Vijaya B.
Published: June 2023

Background

Diagnosis of dementia due to Alzheimer’s disease (AD) is a resource‐intensive process, often requiring clinical assessments and neuroimaging which may fall beyond the reach of patients in remote settings. Given the challenges of traditional dementia work‐up, identification of disease‐relevant signatures from low‐cost modalities has attracted interest as a means to improve disease detection. Here, we describe a machine learning strategy to associate acoustic perturbations in voice with dementia status using digital recordings of neuropsychological exams administered in the Framingham Heart Study (FHS).

Method

We used 118 voice recordings from 79 participants to extract jitter, shimmer, and haronics‐to‐nosie ratio (HNR) from the ComParE 2016 dataset. Each of these acoustic perturbation measures are commonly used in the clinical context to characterize pathological voice. For each voice transcript, these features were computed and and fed as input to a one‐dimensional convolutional neural network to predict dementia status. The data was randomly split in the ratio of 1:1 (at the participant‐level), where 50% of the cases were used for training and the remaining for testing. This process was repeated 10 times and the average model performance was reported. For each model run, the neural network was trained for 500 epochs without early stopping and the model obtained after the final epoch was used for testing.

Result

The mean (±std) age of the participants included in the study was 82.6±8.3 years, and 21 of them were ApoE positive. The mean (±std) area under the receiver operating characteristic curve and the mean (±std) area under the precision‐recall curve of the model classifying participants with dementia from those with normal cognition was 0.673±0.043 and 0.791±0.052, respectively (Fig. 1). Also, the mean accuracy (±std) was 0.615±0.025, the mean precision (±std) was 0.714±0.121, and the mean sensitivity/recall (±std) was 0.721±0.179.

Conclusion

Our study presents a proof‐of‐principle that deep learning on acoustic perturbation measures can predict dementia status. Further studies with additional participants and an expanded set of acoustic, speech and linguistic features are needed to evaluate the full potential of machine learning to derive disease‐relevant signatures from audio data, and potentially expand the reach of early detection and intervention efforts.
Indigenous data sovereignty in the context of big data
Authors: McLester‐Davis Lauren W. Y. , Gleason Carey E. , Blazel Hanna M. , Zuelsdorff Megan , Lambrou Nickolas H. , Parker Tassy
Published: June 2023

Background

Despite evidence that 1 of every 3 American Indian / Alaska Native (AI/AN) elders will develop dementia, they remain substantially underrepresented in Alzheimer’s disease and related dementias (ADRD) research. In our partnership with the Oneida Nation of Wisconsin, scientists from the Wisconsin Alzheimer’s Disease Research Center (ADRC) find ourselves at the intersection of two influential and opposing movements: 1) a movement to ensure Tribal data sovereignty, driven by abuse stemming from unrestricted access to AI/AN data and samples; and 2) researchers' push toward free and unfettered access to big datasets, including genetic data. National ADRD datasets include information from AI/AN participants for whom Tribal affiliation is unknown and there is little to no guidance on how to conduct research with datasets where AI/AN race is identified but Tribal affiliation is unknown. We see a need to establish guidelines for researchers utilizing ADRD big datasets and repositories containing data and samples from AI/AN of unknown Tribal affiliation.

Method

We have contacted stakeholders of ADRD research using AI/AN data of unknown Tribal affiliation, including the National Institute of Aging (NIA) Alzheimer’s Disease Research Centers Program, the NIA Office of Special Populations, the National Alzheimer’s Coordinations Center, the National Centralized Repository for Alzheimer’s Disease and Related Dementias, the National Institute of Health Tribal Health Research Office, and AI/AN scientists who are stakeholders in the use of AI/AN data. Future efforts will involve Alzheimer’s Disease genetic, biomarker sample, and data repositories, and AI/AN elders, youth, and Tribal members.

Result

We plan to develop a process through which proposed analyses that include AI/ANN data will be culturally informed and reviewed by AI/AN scientist ‐ e.g., an AI/AN Advisory Committee. This would ensure that proposals to use AI/AN data and samples from ADRD big datasets and repositories do not inflict further harm to this historically marginalized group. Moreover, the review would ensure that data sovereignty measures are addressed prior to analysis and publication.

Conclusion

We propose to convene an AI/AN Advisory Committee to guide ADRD researchers on culturally responsible management of data, samples, and genetic information collected from AI/AN participants, their Tribes, and their Nations.
68969: Comparative Study Of Neuropsychology、MRI and 18F‐FDG PET in Patients with Alzheimer’s Disease and Semantic Dementia
Authors: Ding Cong , Chen Jianwen , Zhan Yu , Zhao Li , Dong Chunbo
Published: June 2023

Background

Confusion between Alzheimer’s disease (AD) and semantic dementia (SD) in early diagnosis is common, and most previous studies have been based on clinical diagnoses without a pathological diagnosis by biomarkers.

Method

15 patients 18F‐AV 45 PET (+) with AD and 9 patients 18F‐AV 45 PET (‐) with SD enrolled. All patients underwent the following examinations: (1) Neuropsychological tests, including Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL), Boston Nomenclature Test (BNT), and Neuropsychiatric Scale table (NPI). (2) 3.0 head MRI examination, the imaging results were evaluated by MTA‐Scale, Koedam scale, and Kipps scale. (3) 18F‐FDG PET examination, PET images were quantitatively analyzed by Neuro Q software.

Result

ADL score increased in both groups, and the ADL score in the AD group was higher than that in the SD group (P = 0.035). BNT score decreased in both groups, but the BNT score in the SD group was lower than that in the AD group (P = 0.013). There were differences between the two groups in several psycho‐behavioral symptoms; delusions symptoms in the AD group were more prominent than those in the SD group (P = 0.009), and euphoria and disinhibition symptoms in the SD group were more pronounced than AD group (P = 0.015 and 0.015, respectively). The MRI atrophy rating scale showed that the left hippocampus, left frontal lobe, left anterior, and posterior temporal lobe atrophy in the SD group was more severe than that of the AD group (P = 0.018, 0.018, 0.022, and 0.044, respectively). Compared with the two groups of patients, the brain regions with significantly decreased metabolism in the AD group included the right inferior parietal lobule, right posterior cingulate gyrus, and left posterior cingulate gyrus (P = 0.037, 0.014, and 0.037, respectively); the brain regions with significantly decreased metabolism were left inferior frontal gyrus, left medial anterior temporal lobe, right medial anterior temporal lobe, left inferior lateral temporal lobe and left caudate nucleus (P = 0.017, 0.003, 0.037, 0.003, and 0.017, respectively).

Conclusion

Neuropsychology, brain structure, and brain metabolism aid in AD and SD differential diagnosis.
Tuning the properties of breathable polyurethanes through chemical crosslinking
Authors: Kerketta Anjlina , Meena Mahipal , Dwivedi Shivangi , Yadav Raju , Roy Prasun
Published: June 2023

The present work aims at improving the properties of waterproof breathable polyurethane membranes by introducing chemical crosslinks. A series of crosslinked polyurethanes were prepared by chain extension of prepolymer containing varying amounts of a triisocyanate‐based crosslinker (0–15% wt/wt). Thin polyurethane films (~40 μm) were prepared by a solution casting technique and the effect of introducing the crosslinker on thermal, mechanical characteristics was established. Crosslinking led to an increase in glass transition temperature. All crosslinked polyurethanes exhibited a sub‐ambient Tg. Both tensile and tear strengths were found to improve with crosslinking. Crosslinking (15% wt/wt) led to an increase in waterproofness from 112 ± 11 mbar to 574 ± 23 mbar, while the breathability reduced from 1246 ± 52 g/m2/day to 678 ± 32 g/m2/day. Polyurethane membranes containing 10% crosslinker exhibited an optimal balance of waterproofness and breathability, where the film was found to possess a water vapor transmission rate (WVTR) of 834 ± 37 g/m2/day with a hydrostatic pressure of 490 ± 18 mbar. This was subsequently coated on a cotton–polyester fabric to fabricate a breathable textile which was found to exhibit a WVTR of 663 ± 18 g/m2/day and a hydrostatic pressure of >3 bar, which was suitable for practical applications.
Coloration and branching of polypropylene by reactive processing
Authors: Schmidt Lucia N. , Guapacha Jorge , Quinzani Lidia M. , Failla Marcelo D.
Published: June 2023

Reactive melt processing is a known technique used to produce long‐chain branched polypropylene. It involves polyfunctional substances that act as chain‐linking agents (CA). In this work, polyfunctional amine dyes are used as CA in a novel method for simultaneously improving melt strength and fade resistance of polypropylene. Colored long‐chain branched polymer is synthesized by reactive processing of maleic anhydride grafted polypropylene (PPg) in the molten state using glycerol, basic fuchsin and disperse blue 1. Selected CA concentrations avoid gel‐like structures and impart good color intensity. FT‐IR spectroscopy confirms the reaction between PPg and the CAs while rheological characterization supports the synthesis of long‐chain branched structures. Covalent bonding of dye molecules to PPg is confirmed by both UV–visible spectroscopy and colorimetry. A maximum total color difference, ∆E*, of about 20 was measured after xylene purification. New materials show good color homogeneity and transparency with minimum bleeding after 48 hours exposure to water and ethanol.
Evaluation safety and efficacy of immune checkpoint blockers (ICB) and radiotherapy combination versus ICB in non‐small cell lung cancer patients with recurrence or metastasis: A systematic review and meta‐analysis
Authors: Zeng Yichun , Zhang Liying , Liang Yichen , Zhang Xian , Li Lei , Wang Maoqi , Guo Jingliang , Li Qiuxian , Cao Jin , Gu Juan J. , Wang Buhai
Published: June 2023

Background

Currently, immune checkpoint blockers (ICB) and radiotherapy (RT) combination therapy is broadly applied in non‐small cell lung cancer (NSCLC) patients. However, meta‐analysis about safety and efficacy of RT + ICB versus ICB has not yet been reported. To evaluate safety and efficacy of the combination therapy of ICB and RT in patients with recurrent or metastatic NSCLC and explore factors related to higher response rates, longer lifetime, and lower toxicity, meta‐analysis of previous clinical data will be presented in this article.

Methods

A literature search on patients with recurrent or metastatic NSCLC treated with RT + ICB versus ICB was performed using the Cochrane Library, Embase and PubMed up to December 10, 2022. Suitable quality assessment checklists were selected corresponding to various types of research studies. Comparative and single‐arm studies were analyzed using Stata 14.0.

Results

10 comparative studies and 15 arms of combination therapy were included for this meta‐analysis. RT significantly improved objective response rate (ORR), disease control rate (DCR), and overall survival (OS) and progression‐free survival (PFS) of ICB (I‐square value (I2) = 0.00%, odds ratio (OR) 1.28, 95% confidence interval (CI) 1.09–1.49, I2 = 0.00%, OR 1.12, 95% CI 1.00–1.25, I2 = 42.1%, OR 0.81, 95% CI 0.72–0.92, I2 = 34.5%, OR 0.80, and 95% CI 0.71–0.89, respectively). Toxicity between combination therapy and ICB monotherapy did not significantly differ in any grade or in ≥3 grade of tr‐AEs (I2 = 0.00%, OR 1.05, 95% CI 0.91–1.22, I2 = 0.00%, OR 1.46, 95% CI 0.90–2.37, respectively). Subgroup analyses based on single‐arm studies showed that applications of SRS/SBRT, PD‐1 inhibitor, and administration of ICB after RT were conducive to a better DCR, longer OS and mild adverse events (heterogeneity between groups (HBG) all p < 0.05).

Conclusion

RT can significantly improve ORR, DCR, OS, and PFS of ICB in patients with recurrent or metastatic NSCLC without increasing toxicity. PD‐1 inhibitor following SRS/SBRT could be the best option to maximally benefit the patients.
Multiple types of distress are prospectively associated with increased risk of ovarian cancer
Authors: Roberts Andrea L. , Ratanatharathorn Andrew , Chibnik Lori , Kubzansky Laura D. , Tworoger Shelley S.
Published: June 2023

Background

Few modifiable risk factors for epithelial ovarian cancer have been identified. We and other investigators have found that individual psychosocial factors related to distress are associated with higher risk of ovarian cancer. The present study examined whether co‐occurring distress‐related factors are associated with ovarian cancer risk.

Methods

Five distress‐related factors were measured repeatedly over 21 years of follow‐up: depression, anxiety, social isolation, widowhood, and, in a subset or women, posttraumatic stress disorder (PTSD). Cox proportional hazards models estimate relative risks (RR) and 95% confidence intervals (CI) of ovarian cancer for a time‐updated count of distress‐related factors, in age‐adjusted models, then further adjusted for ovarian cancer risk factors and behavior‐related health risk factors.

Results

Across 1,193,927 person‐years of follow‐up, 526 incident ovarian cancers occurred. Women with ≥3 versus no distress‐related psychosocial factors demonstrated increased ovarian cancer risk (HRage‐adjusted = 1.71; 95% CI = 1.16, 2.52). No significant difference in ovarian cancer risk was observed in women with one or two versus no distress‐related psychosocial factors. In the subsample with PTSD assessed, ≥3 versus no distress‐related psychosocial factors was associated with twofold greater ovarian cancer risk (HRage‐adjusted = 2.08, 95% CI = 1.01, 4.29). Further analysis suggested that women at highest ovarian cancer risk had PTSD co‐occurring with any other distress‐related factor (HR = 2.19, 95% CI = 1.20, 4.01). Adjusting for cancer risk factors and health behaviors minimally impacted risk estimates.

Conclusions

Presence of multiple indicators of distress was associated with risk of ovarian cancer. When including PTSD as an indicator of distress, the association was strengthened.
Predictive significance of lymphocyte level and neutrophil‐to‐lymphocyte ratio values during radiotherapy in cervical cancer treatment
Authors: Zhao Mengli , Gao Zhongrong , Gu Xiaowei , Yang Xiaojing , Wang Shanshan , Fu Jie
Published: June 2023

Objective

The objective of this research was to analyze the prognostic significance of the minimum count of lymphocytes (LY) and the corresponding ratio of neutrophil‐to‐lymphocyte (NLR) in cervical cancer (CC) patients receiving radiotherapy.

Methods

We retrospectively collected data from 202 CC patients who received concurrent chemoradiotherapy or radiotherapy alone at our hospital. Statistical methods including the Kaplan–Meier method, log‐rank test and the Cox proportional hazards model were included to examine survival differences and identify independent factors that may affect overall survival (OS) and progression‐free survival (PFS).

Results

The research enrolled a total of 202 patients. Patients with higher LY levels and lower NLR values during radiotherapy had significantly better survival prognosis than those with lower LY levels and higher NLR values. Multivariate COX regression analysis revealed that FIGO stage I, pathological types of SqCC, absence of lymph node metastasis, concurrent chemoradiotherapy, higher LY levels during radiotherapy, and lower NLR values before radiotherapy were independently associated with poorer PFS. Similarly, FIGO stage I, absence of lymph node metastasis and lower NLR values during and before radiotherapy were independently linked with poorer OS.

Conclusion

Minimum LY value and its corresponding NLR during radiotherapy serve as prognostic factors for CC.
Influence of pathogens on host genome and epigenome in development of head and neck cancer
Authors: Desai Sanket
Published: June 2023

Background

Head and neck cancer (HNSCC) is a heterogeneous group of cancers, affecting multiple regions such as oral cavity, pharynx, larynx, and nasal region, each showing a distinct molecular profile. HNSCC accounts for more than 6 million cases worldwide, soaring mainly in the developing countries.

Recent findings

The aetiology of HNSCC is complex and multifactorial, involving both genetic and environmental factors. The critical role of microbiome, which includes bacteria, viruses, and fungi, is under spotlight due to the recent reports on their contribution in the development and progression of HNSCC. This review focuses on the effect of opportunistic pathogens on the host genome and epigenome, which contributes to the disease progression. Drawing parallels from the host‐pathogen interactions observed in other tumour types arising from the epithelial tissue such as colorectal cancer, the review also calls attention to the potential explorations of the role of pathogens in HNSCC biology and discusses the clinical implications of microbiome research in detection and treatment of HNSCC.

Conclusion

Our understanding of the genomic effects of the microbes on the disease progression and the mechanistic insights of the host‐pathogen interaction will pave way to novel treatment and preventive approaches in HNSCC.
Human mesenchymal stem‐derived extracellular vesicles improve body growth and motor function following severe spinal cord injury in rat
Authors: Nakazaki Masahito , Lankford Karen L. , Yamamoto Hideaki , Mae Yoshiyuki , Kocsis Jeffery D.
Published: June 2023

Background

Spinal cord injury (SCI) in young adults leads to severe sensorimotor disabilities as well as slowing of growth. Systemic pro‐inflammatory cytokines are associated with growth failure and muscle wasting. Here we investigated whether intravenous (IV) delivery of small extracellular vesicles (sEVs) derived from human mesenchymal stem/stromal cells (MSC) has therapeutic effects on body growth and motor recovery and can modulate inflammatory cytokines following severe SCI in young adult rats.

Methods

Contusional SCI rats were randomized into three different treatment groups (human and rat MSC‐sEVs and a PBS group) on day 7 post‐SCI. Functional motor recovery and body growth were assessed weekly until day 70 post‐SCI. Trafficking of sEVs after IV infusions in vivo, the uptake of sEVs in vitro, macrophage phenotype at the lesion and cytokine levels at the lesion, liver and systemic circulation were also evaluated.

Results

An IV delivery of both human and rat MSC‐sEVs improved functional motor recovery after SCI and restored normal body growth in young adult SCI rats, indicating a broad therapeutic benefit of MSC‐sEVs and a lack of species specificity for these effects. Human MSC‐sEVs were selectively taken up by M2 macrophages in vivo and in vitro, consistent with our previous observations of rat MSC‐sEV uptake. Furthermore, the infusion of human or rat MSC‐sEVs resulted in an increase in the proportion of M2 macrophages and a decrease in the production of the pro‐inflammatory cytokines tumour necrosis factor‐alpha (TNF‐α) and interleukin (IL)‐6 at the injury site, as well as a reduction in systemic serum levels of TNF‐α and IL‐6 and an increase in growth hormone receptors and IGF‐1 levels in the liver.

Conclusions

Both human and rat MSC‐sEVs promote the recovery of body growth and motor function after SCI in young adult rats possibly via the cytokine modulation of growth‐related hormonal pathways. Thus, MSC‐sEVs affect both metabolic and neurological deficits in SCI.
Neuroblastoma in uncommon age group – A case series diagnosed on cytology
Authors: Dharmalingam Priya , Chenniappan Aparna Devi , Alashetty Soumya , Bidadi Lingappa Kavitha , Patil Okaly Geeta V.
Published: June 2023

Background

Neuroblastoma is the most common extracranial malignant neoplasm in early childhood. It is rare in the adult population.

Aims and Objectives

We aimed to study the incidence of neuroblastoma in the uncommon age group diagnosed on cytology.

Materials and Methods

A prospective descriptive study spanning 2 years from December 2020 to January 2022 was done, in which neuroblastoma cases diagnosed by Fine needle aspiration cytology aged >12 years were collected. The clinical, cytomorphological and immunohistochemical findings were studied. Histopathological correlation was done wherever available.

Results

We identified three cases of neuroblastoma during this period. Two cases were middle‐aged adults, and one was an adolescent. All cases presented with abdominal masses and revealed small round cell tumor on cytology. Two cases fell into undifferentiated category and one case fell into the poorly differentiated subtype. All cases were positive for neuroendocrine markers. Histopathological correlation was available in two cases. MYC N amplification was absent in all cases.

Conclusion

It differs from pediatric neuroblastoma due to the lack of classical histomorphological features and molecular alterations. Adult‐onset neuroblastomas carry a worse prognosis than childhood tumors.
Adoption and feeding of fieldfare nestlings and fledglings by European blackbird
Authors: Wysocki Dariusz , Wawryniuk Katarzyna , Cieślińska Karolina , Wojczulanis‐Jakubas Katarzyna
Published: June 2023

Interspecific adoption is an intriguing topic in behavioral and evolutionary ecology. As it is a rare phenomenon, seldom documented in the literature, reports of interspecific adoption based on solid data are particularly valuable. A long‐term and extensive monitoring programme involving a local population of European blackbirds (Turdus merula, hereafter blackbird) has yielded, among other things, observations of alloparental behavior exhibited by blackbirds toward fieldfare (Turdus pilaris) nestlings (a single nest, the first‐ever record) and fledglings (12 cases in all). We discuss the observations in the context of the available literature.
Benefits of the four‐day workweek
Authors: Freebairn‐Smith Laura
Published: June 2023

In this month's column, which is adapted from my forthcoming book, Abundance Leaders: Creating Energy, Joy, and Productivity in an Unsettled World, which Wiley is releasing in the fall of 2023, I will discuss the four‐day work week.
Current and preservice teachers' views and beliefs regarding martial arts and the inclusion of martial arts in Australian school settings: A cross‐sectional study
Authors: Burt Louis , Riley Nicholas , Eather Narelle
Published: June 2023

Purpose

This study investigates views and beliefs of current and preservice teachers regarding martial arts (MA) and the inclusion of martial arts in schools.

Methods

Participants completed an anonymous, 28‐item questionnaire made available online via Qualtrics (August–November 2020). Data was analysed using SPSS software to compare mean scores by sex, and between qualified teachers and preservice teachers. Qualitative data in the form of quotes was drawn upon and used to complement the quantitative results.

Results

Results indicate teachers and preservice teachers view MA as a worthwhile and beneficial activity for school‐aged students, and support the inclusion of MA into school settings.

Conclusion

These findings may be useful to inform policy and practice in schools, and the development of teacher education programs, professional development courses, and school‐based education programs utilizing MA to meet physical education learning outcomes.
A case of retroperitoneal liposarcoma extending through the inguinal canal to the thigh and lesser trochanter
Authors: Maekawa Takahiro , Yamamoto Yoshiyuki , Kato Taigo , Hatano Koji , Kawashima Atsunari , Fukuhara Shinichiro , Imamura Ryoichi , Nonomura Norio
Published: June 2023

Introduction

Liposarcoma is the most common retroperitoneal soft tissue tumor. Liposarcomas are often asymptomatic and are discovered after they become huge. Surgical resection is the first‐line treatment for retroperitoneal liposarcoma, but the surrounding organs are often resected with the liposarcoma.

Case presentation

A man saw a hospital with a complaint of left lower abdominal distention, and a left retroperitoneal mass was noted on imaging examination. The patient was referred to our hospital. The mass extended from the retroperitoneum through the inguinal canal to the thigh and involved the femoral nerve and psoas major muscle. A well‐differentiated liposarcoma was suspected, and an open surgical resection was performed. Complete resection of a retroperitoneal liposarcoma extending to the thigh was achieved without postoperative complications.

Conclusion

Treatment strategies for huge retroperitoneal liposarcomas are important to balance antitumor efficacy and postoperative quality of life.
Reflective functioning and mother–infant relationships among mothers with Borderline Personality Disorder post‐therapy
Authors: Osborne Jo , Mattiske Julie , Winter Amelia , Sved Williams Anne
Published: June 2023

The stressful nature of parenting infants exacerbates the characteristics of Borderline Personality Disorder (BPD). Consequently, mothers with BPD tend to be emotionally dysregulated, respond impulsively to their infants, and have poorer mother–infant relationships. Few parenting interventions target the specific skill deficits observed in mothers with BPD. This study explored the differences in parental reflective functioning (PRF) and mother–infant relationship quality at baseline and following a 24‐week, group parenting intervention for mothers with BPD. PRF and mother‐infant relationship quality were assessed from quantitative (N = 23) and qualitative (N = 32) perspectives. Quantitative data (Parental Reflective Functioning Questionnaire) showed a significant improvement in one of the three subscales, Interest and Curiosity, between baseline and post‐intervention, and a significant moderate positive association between the subscale Certainty of Mental States and maternal‐infant interaction quality post‐intervention. Improvements in mother‐infant relationship quality were not evident from the observational measure, Nursing Child Assessment Satellite Teaching scale. In contrast, semi‐structured interview qualitative data found maternal improvements in parental reflection, coping strategies implemented post‐intervention, and quality of mother–infant relationships. Overwhelmingly positive intervention feedback suggested perceived maternal benefits of group format and skills taught. Future studies with larger sample sizes would allow further clarification of such parenting interventions for mothers with BPD.
Quantitative phase imaging of living red blood cells combining digital holographic microscopy and deep learning
Authors: Zhao Jiaxi , Liu Lin , Wang Tianhe , Zhang Jing , Wang Xiangzhou , Du Xiaohui , Hao Ruqian , Liu Juanxiu , Liu Yi , Liu Yong
Published: June 2023

Digital holographic microscopy as a non‐contacting, non‐invasive, and highly accurate measurement technology, is becoming a valuable method for quantitatively investigating cells and tissues. Reconstruction of phases from a digital hologram is a key step in quantitative phase imaging for biological and biomedical research. This study proposes a two‐stage deep convolutional neural network named VY‐Net, to realize the effective and robust phase reconstruction of living red blood cells. The VY‐Net can obtain the phase information of an object directly from a single‐shot off‐axis digital hologram. We also propose two new indices to evaluate the reconstructed phases. In experiments, the mean of the structural similarity index of reconstructed phases can reach 0.9309, and the mean of the accuracy of reconstructions of reconstructed phases is as high as 91.54%. An unseen phase map of a living human white blood cell is successfully reconstructed by the trained VY‐Net, demonstrating its strong generality.