bluuebunny/crossref_metadata_2025 huggingface dataset:
Medical and nursing home costs: From cognitively unimpaired through dementia
Authors: Long Kirsten Hall , Smith Carin , Petersen Ronald , Emerson Jane , Ransom Jeanine , Mielke Michelle M. , Hass Steven , Leibson Cynthia
Published: September 2021

Introduction

Efforts to model the cost‐effectiveness of managing/modifying cognitive impairment lack reliable, objective, baseline medical, and nursing‐home (NH) costs.

Methods

A stratified‐random sample of Olmsted County, MN, residents ages 70–89 years (N = 3545), well‐characterized as cognitively unimpaired, mild cognitive impairment (MCI), or dementia, were followed forward ≤1 year in provider‐linked billing data and the Centers for Medicare & Medicaid Services NH assessments. Direct medical/nursing home/medical + NH costs were estimated. Costs were stratified by vital status and NH‐use intensity (NH days/follow‐up days [0%, 1% to 24%, 25% to 99%, and 100%]). Between‐category mean‐annual cost differences were adjusted for patient characteristics and follow‐up days.

Results

Costs/follow‐up day distributions differed significantly across cognitive categories. Mean costs/follow‐up days were 2.5 to 18 times higher for decedents versus survivors. Among all persons with MCI, <9% with any NH use accounted for 18% of all total annual medical + NH costs. Adjusted‐between‐category comparisons revealed significantly higher medical and medical + NH costs for MCI versus cognitively unimpaired.

Discussion

Cost‐effectiveness for managing/modifying both MCI and dementia should consider end‐of‐life costs and NH‐use intensity. Results can help inform cost‐effectiveness models, predict future‐care needs, and aid decision‐making by individuals/providers/payers/policymakers.
Epigenomic features related to microglia are associated with attenuated effect ofAPOEε4 on Alzheimer's disease risk in humans
Authors: Ma Yiyi , Yu Lei , Olah Marta , Smith Rebecca , Oatman Stephanie R. , Allen Mariet , Pishva Ehsan , Zhang Bin , Menon Vilas , Ertekin‐Taner Nilüfer , Lunnon Katie , Bennett David A. , Klein Hans‐Ulrich , De Jager Philip L.
Published: September 2021

Not all apolipoprotein E (APOE) ε4 carriers who survive to advanced age develop Alzheimer's disease (AD); factors attenuating the risk of ε4 on AD may exist. Guided by the top ε4‐attenuating signals from methylome‐wide association analyses (N = 572, ε4+ and ε4–) of neurofibrillary tangles and neuritic plaques, we conducted a meta‐analysis for pathological AD within the ε4+ subgroups (N = 235) across four independent collections of brains. Cortical RNA‐seq and microglial morphology measurements were used in functional analyses. Three out of the four significant CpG dinucleotides were captured by one principal component (PC1), which interacts with ε4 on AD, and is associated with expression of innate immune genes and activated microglia. In ε4 carriers, reduction in each unit of PC1 attenuated the odds of AD by 58% (odds ratio = 2.39, 95% confidence interval = [1.64,3.46],P = 7.08 × 10–6). An epigenomic factor associated with a reduced proportion of activated microglia (epigenomic factor of activated microglia, EFAM) appears to attenuate the risk of ε4 on AD.
Associations among vascular risk factors, neuroimaging biomarkers, and cognition: Preliminary analyses from the Multi‐Ethnic Study of Atherosclerosis (MESA)
Authors: Lockhart Samuel N. , Schaich Christopher L. , Craft Suzanne , Sachs Bonnie C. , Rapp Stephen R. , Jung Youngkyoo , Whitlow Christopher T. , Solingapuram Sai Kiran Kumar , Cleveland Maryjo , Williams Benjamin J. , Burke Gregory L. , Bertoni Alain , Hayden Kathleen M. , Hughes Timothy M.
Published: September 2021

Introduction

Little is known about how antecedent vascular risk factor (VRF) profiles impact late‐life brain health.

Methods

We examined baseline VRFs, and cognitive testing and neuroimaging measures (β‐amyloid [Aβ] PET, MRI) in a diverse longitudinal cohort (N = 159; 50% African‐American, 50% White) from Wake Forest's Multi‐Ethnic Study of Atherosclerosis Core.

Results

African‐Americans exhibited greater baseline Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham stroke risk profile (FSRP), and atherosclerotic cardiovascular disease risk estimate (ASCVD) scores than Whites. We observed no significant racial differences in Aβ positivity, cortical thickness, or white matter hyperintensity (WMH) volume. Higher baseline VRF scores were associated with lower cortical thickness and greater WMH volume, and FSRP and CAIDE were associated with Aβ. Aβ was cross‐sectionally associated with cognition, and all imaging biomarkers were associated with greater 6‐year cognitive decline.

Discussion

Results suggest the convergence of multiple vascular and Alzheimer's processes underlying neurodegeneration and cognitive decline.
Cognitive decline as an outcome and marker of progression toward dementia, in early preventive trials
Authors: Mura Thibault , Coley Nicola , Amieva Hélène , Berr Claudine , Gabelle Audrey , Ousset Pierre‐Jean , Vellas Bruno , Andrieu Sandrine ,   for the GuidAge/DSA study group*
Published: September 2021

Introduction

Recent Food and Drug Administration guidance endorses cognitive assessment as a possible primary endpoint for early trials for Alzheimer's disease but emphasizes the need for certainty regarding the relationship with progression to dementia.

Methods

We compared the validity of the 2‐year change (Y0–Y2) of 11 markers of neuropsychological and functional abilities for the prediction of incident dementia over the following 3 years (Y2–Y5), in 860 subjects aged 70 years or older, who consulted for memory loss and were included in the “GuidAge” prevention trial.

Results

The Free and Cued Selective Reminding Test–Free Recall (FCSRT‐FR) score showed the most predictive 2‐year change (area under the curve = 0.72 95% confidence interval = 0.64;0.81). Changes in other subscores of the FCSRT, verbal fluencies tasks, and composite cognitive score were also significantly predictive. Conversely, 2‐year change of Mini‐Mental State Examination, Trail Making test (TMT)‐A, TMT‐B, Clinical Dementia Rating Sum of Boxes, and Instrumental Activities of Daily Living scores did not significantly predict occurrence of dementia.

Conclusion

The FCSRT, the Fluency Task, and the composite cognitive score appear to be good cognitive markers of progression toward dementia in early prevention trials.
Association between Alzheimer's disease and risk of cancer: A retrospective cohort study in Shanghai, China
Authors: Ren Ru‐Jing , Huang Qiang , Xu Gang , Gu Kai , Dammer Eric B. , Wang Chun‐Fang , Xie Xin‐Yi , Chen Wen , Shao Zhen‐Yi , Chen Sheng‐Di , Wang Gang
Published: September 2021

Introduction

We investigated the association between Alzheimer's disease (AD) and the risk of cancer in the Chinese population.

Methods

In this retrospective cohort study, multivariate Cox proportional hazard regression analysis was used to determine the correlation between AD and the risk of various cancers, as shown by hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

Of 8097 AD patients, the HR for all subsequent cancers was 0.822 (95% CI, 0.728‐0.928; P = .002). Among them, three specific cancers were associated with AD: lung cancer (HR, 0.656; 95% CI, 0.494‐ 0.871; P = .004), prostate and testicular cancer (HR, 0.414; 95% CI, 0.202‐0.847; P = .016), and lymphoma (HR, 2.202; 95% CI, 1.005‐4.826; P = .049).

Conclusion

Patients with AD might have a lower chance of developing several cancers, including lung cancer and prostate and testicular cancer. Meanwhile, a positive association between AD and a higher incident rate of lymphoma was observed.
Why the cognitive “fountain of youth” may be upstream: Pathways to dementia risk and resilience through social connectedness
Authors: Perry Brea L. , McConnell Will R. , Coleman Max E. , Roth Adam R. , Peng Siyun , Apostolova Liana G.
Published: September 2021

Research suggests social connectedness may help older adults with dementia maintain cognitive functionality and quality of life. However, little is known about its specific social and biological mechanisms. This paper proposes two pathways through social bridging (i.e., cognitive enrichment through expansive social networks) and bonding (i.e., neuroendocrine benefits of integration in cohesive social networks). We provide preliminary evidence for these pathways using neuroimaging, cognitive, and egocentric social network data from the Social Networks and Alzheimer's Disease (SNAD) study (N = 280). We found that network size, density, and presence of weak ties (i.e., social bridging) moderated the association between brain atrophy and cognitive function, while marriage/cohabitation (i.e., social bonding) moderated the association between perceived stress and cognitive function. We argue that social connectedness may have downstream implications for multiple pathophysiological processes in cognitive aging, even negating existing structural damage to the brain, making it a strong candidate for clinical or policy intervention.
Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain
Authors: Logsdon Aric F. , Francis Kendra L. , Richardson Nicole E. , Hu Shannon J. , Faber Chelsea L. , Phan Bao Anh , Nguyen Vy , Setthavongsack Naly , Banks William A. , Woltjer Randy L. , Keene C. Dirk , Latimer Caitlin S. , Schwartz Michael W. , Scarlett Jarrad M. , Alonge Kimberly M.
Published: September 2021

The extracellular matrix (ECM) of the brain comprises unique glycan “sulfation codes” that influence neurological function. Perineuronal nets (PNNs) are chondroitin sulfate‐glycosaminoglycan (CS‐GAG) containing matrices that enmesh neural networks involved in memory and cognition, and loss of PNN matrices is reported in patients with neurocognitive and neuropsychiatric disorders including Alzheimer's disease (AD). Using liquid chromatography tandem mass spectrometry (LC‐MS/MS), we show that patients with a clinical diagnosis of AD‐related dementia undergo a re‐coding of their PNN‐associated CS‐GAGs that correlates to Braak stage progression, hyperphosphorylated tau (p‐tau) accumulation, and cognitive impairment. As these CS‐GAG sulfation changes are detectable prior to the regional onset of classical AD pathology, they may contribute to the initiation and/or progression of the underlying degenerative processes and implicate the brain matrix sulfation code as a key player in the development of AD clinicopathology.
Polyhexamethylene biguanide hydrochloride anchored polymeric elastic fibers with robust antibacterial performance
Authors: Gong Da‐Kai , Zhang Ao , Luo Hao , Shi Yi‐Dong , Zhang Yong , Tan Lin
Published: September 2021

Elastic fibers have been widely applied for the fabrication of biomedical textiles, artificial extracellular matrix, and functional garments, as where antibacterial property is one of the indispensable features. Herein, we developed a fresh type of non‐leaching antibacterial fiber that could effectively inactivate bacteria with durable performance to circumvent above concerns. In detail, we firstly synthesized a precursor polymer (PS‐GMA) based on styrene and glycidyl methacrylate (GMA) through free radical polymerization, then blended PS‐GMA with thermoplastic polyurethane (TPU) and processed the blend into fiber through wet spinning technology. Finally, the obtained fiber was covalently modified by polyhexamethylene biguanide hydrochloride (PHMB). The experimental results showed that the resultant fiber (named as PGPs) exhibited a strong bactericidal ability to both Staphylococcus aureus and Escherichia coli, as well as maintained excellent antibacterial properties even after ultraviolet irradiation for 7 days or 50 washing cycles. Furthermore, we explored the sterilization mechanism with respect to the bacterial morphologies and the activity of the respiratory chain dehydrogenase. In addition, the biocidal efficacy of the prepared fiber could remain approximately 100% after eight consecutive antibacterial cycles. Collectively, this work exhibited an attempt in exploitation of the intrinsically antibacterial fiber with long‐run function duration by an economical tactic.
Clustering high‐frequency financial time series based on information theory
Authors: Liu Haitao , Zou Jian , Ravishanker Nalini
Published: September 2021

Clustering large financial time series data enables pattern extraction that facilitates risk management. The knowledge gathered from unsupervised learning is useful for improving portfolio optimization and making stock trading recommendations. Most methods available in the literature for clustering financial time series are based on exploiting linear relationships between time series. However, prices of different assets (stocks) may have non‐linear relationships which may be quantified using information based measures such as mutual information (MI). To estimate the empirical mutual information between time series of stock returns, we employ a novel kernel density estimator (KDE) based jackknife mutual information estimation (JMI), and compare it with the widely‐used binning method. We then propose an average distance gradient change algorithm and an algorithm based on the average silhouette criterion that use pairwise and groupwise MI of high‐frequency financial stock returns. Through numerical studies, we provide insights into the impact of the clustering on asset allocation and risk management based on the nonlinear information structure of the US stock market.
Metabolomics reveals the role of isopentenyl group in coumarins metabolism
Authors: Ma Xiao‐fang , Zhao Qi , Cheng Yan , Yan Dong‐Mei , Zhu Wei‐Feng , Li Fei
Published: September 2021

Coumarins are a group of natural compounds commonly found in the families of Rutaceae and Umbelliferae. 7‐Isopentenyloxycoumarin (ISC), auraptene (AUR), and umbelliprenin (UM) belong to prenyloxycoumarins (PYCs), which link isopentenyl, geranyl, and farnesyl group at C7 position, respectively. The substituent of 7‐ethoxycoumarin (ETC) is the ethyl group. In this study, UPLC–ESI–QTOF–MS (ultra‐performance liquid chromatography–electrospray ionization–quadrupole time of flight–MS)‐based metabolomics was used to evaluate the in vivo and in vitro metabolism of PYCs. Results showed that ETC produced 10 known metabolites, and ISC was transformed into 17 metabolites in vivo and in vitro, which were undescribed compounds. A total of 35 AUR metabolites, including 34 undescribed metabolites were identified, and 21 metabolites were reported for the first time in UM. The results indicated that hydroxylation and N‐acetylcysteine conjugation were the common metabolic reactions for PYCs. The metabolic rates of ETC, ISC, AUR and UM were 26%, 36%, 81%, and 38%, respectively, in human liver microsome, while they were 24%, 40%, 80%, and 37%, respectively, in mouse liver microsomes. In addition, recombinant cytochrome P450s (CYPs) screening showed that CYP1A1, 2C19, 3A4, and 3A5 were the major metabolic enzymes involved in the formation of hydroxylation metabolites. Together, these results suggest that the isopentenyl group plays an important role in the metabolism of PYCs.
Motivation and learning methods of anatomy: Associations with mental well‐being
Authors: Fives Cassie , Lone Mutahira , Nolan Yvonne M.
Published: September 2021

Appropriate anatomy education for speech and language therapists is a crucial part of preparation for clinical practice. While much research has been conducted regarding the anatomical education of medical students, there is a paucity of evidence for speech and language therapy students. This study assessed the methods employed by a cohort of first‐year speech and language therapy students to learn anatomy, their perceptions of the clinical importance of anatomy and motivation to learn anatomy (using a modified version of the motivation strategies for learning questionnaire) and how this related to potential barriers to motivation such as mental well‐being (using the Warwick‐Edinburgh Mental Well‐Being Scale [WEMWBS]). Analysis revealed that 92% of students agreed or strongly agreed that a sound knowledge of anatomy is important for clinical practice, 74% agreed or strongly agreed that listening at lectures was how they primarily learned anatomy, and 91% of students agreed or strongly agreed that they worried a great deal about tests. The latter statement was negatively correlated with a number of statements on the WEMWBS. Overall, the data revealed that first‐year speech and language therapy students place importance on anatomy and its role in their future clinical practice, that they have different preferences for learning anatomy compared to medical students, and also have significant anxiety surrounding anatomy examinations. Multiple significant correlations between responses to the motivation and mental well‐being questionnaires suggest that there is a significant relationship between first‐year student motivation to learn anatomy and well‐being.
Identification and validation of RNA‐binding protein‐related gene signature revealed potential associations with immunosuppression and drug sensitivity in glioma
Authors: Chen Zhuohui , Wu Haiyue , Yang Haojun , Fan Yishu , Zhao Songfeng , Zhang Mengqi
Published: September 2021

Background

Glioma is the most common central nervous system tumor in adults, and a considerable part of them are high‐degree ones with high malignancy and poor prognosis. At present, the classification and treatment of glioma are mainly based on its histological characteristics, so studies at the molecular level are needed.

Methods

RNA‐seq data from The Cancer Genome Atlas (TCGA) datasets (n = 703) and Chinese Glioma Genome Atlas (CGGA) were utilized to find out the differentially expressed RNA‐binding proteins (RBPs) between normal cerebral tissue and glioma. A prediction system for the prognosis of glioma patients based on 11 RBPs was established and validated using uni‐ and multi‐variate Cox regression analyses. STITCH and CMap databases were exploited to identify putative drugs and their targets. Single sample gene set enrichment analysis (ssGSEA) was used to calculate scores of specific immune‐related gene sets. IC50 of over 20,000 compounds in 60 cancer cell lines was collected from the CellMiner database to test the drug sensitivity prediction value of the RBP‐based signature.

Results

We established a reliable prediction system for the prognosis of glioma patients based on 11 RBPs including THOC3, LSM11, SARNP, PABPC1L2B, SMN1, BRCA1, ZC3H8, DZIP1L, HEXIM2, LARP4B, and ZC3H12B. These RBPs were primarily associated with ribosome and post‐transcriptional regulation. RBP‐based risk scores were closely related to immune cells and immune function. We also confirmed the potential of the signature to predict the drug sensitivity of currently approved or evaluated drugs.

Conclusions

Differentially expressed RBPs in glioma can be used as a basis for prognosis prediction, new drugs screening and drug sensitivity prediction. As RBP‐based glioma risk scores were associated with immunity, immunotherapy may become an important treatment for glioma in the future.
Acute psychosis secondary to steroid responsive encephalopathy associated with autoimmune Hashimoto's thyroiditis
Authors: Ibrahim Shahd I. , Khalafalla Alaa M. , Safan Abeer S. , Alsaud Arwa E. , B.Batia Tala , Yassin Mohamed A.
Published: September 2021

Approach to Hashimoto thyroiditis encephalopathy.
Gastrointestinal infantile hemangioma: A rare cause of digestive tract bleeding in children to consider
Authors: Cura‐Esquivel Idalia , Velasquez‐Palacios Carlos , Núñez‐Ku Madeline
Published: September 2021

Intestinal hemangiomas are an infrequent cause of gastrointestinal bleeding and chronic anemia in infants, which diagnosis depends on high suspicion. Propranolol has been described as an effective treatment.
Mite is right: A case of infected scabies masquerading as a blistering disorder
Authors: Tameez‐ud‐din Ahsan , Tameez Ud Din Asim , Malik Ifrah
Published: September 2021

Scabies classically presents with itching and skin lesions in the interdigital spaces of hands, trunk, and genitals. Rarely, non‐classical skin lesions can result in misdiagnosis and inappropriate management of patients.
Case series: Rare cases of thyroid storm in COVID‐19 patients
Authors: Milani Nasrin , Najafpour Maryam , Mohebbi Masoud
Published: September 2021

Thyroid storm is an uncommon life‐threatening thyroid dysfunction which was observed for the first time among patients infected with Coronavirus 2019 (COVID‐19). The diagnosis and treatment of the rare thyroid distinctions such as thyroid storm in COVID‐19–infected patients should be critically considered alongside common treatments of COVID‐19 infection.
Barium‐induced pneumatosis intestinalis in a patient with anti‐synthetase syndrome
Authors: Yamamoto Shintaro , Mukai Tomoyuki , Fujita Shunichi , Morita Yoshitaka
Published: September 2021

Pneumatosis intestinalis is defined as the presence of gas in the bowel wall. The combination of the two risks, pre‐existing connective tissue diseases and barium contrast examination, may trigger pneumatosis intestinalis, albeit at a low incidence. Clinicians should be aware of the condition for proper differential diagnosis.
Ruxolitinib for treatment of polycythemia vera and myelofibrosis in patients after liver transplantation
Authors: Dold Leona , Lutz Philipp , Heine Annkristin , Weismüller Tobias J. , Strassburg Christian P. , Spengler Ulrich
Published: September 2021

Although ruxolitinib contributes to immunomodulation and can lead to severe infections, it seems a feasible treatment strategy for patients with polycythemia vera and myelofibrosis after liver transplantation.
Goblet cell carcinoma of appendix detected during surgery for ovarian tumors
Authors: Kawase Rieko , Suzuki Shunji
Published: September 2021

An appendectomy with a thorough examination of the gastrointestinal tract should be performed in women with a mucinous ovarian tumor.
A pregnant woman with a history of SLE with PPROM and severe thrombocytopenia: A case study
Authors: Farahani Masoumeh , Maghoul Arman , Nirouei Matineh , Alinia Tina
Published: September 2021

This study discusses the management of a pregnant woman with PPROM and a history of lupus. She was found to be severely thrombocytopenic which was unresponsive to prednisolone. During cesarean section, placental abruption was found and postpartum hemorrhage ensued.
Electrosynthesis of Azobenzenes Directly from Nitrobenzenes
Authors: Ma Yanfeng , Wu Shanghui , Jiang Shuxin , Xiao Fuhong , Deng Guo‐Jun
Published: September 2021

Main observation and conclusion

The electrochemical reduction strategy of nitrobenzenes is developed. The chemistry occurs under ambient conditions. The protocol uses inert electrodes and the solvent, DMSO, plays a dual role as a reducing agent. Its synthetic value has been demonstrated by the highly efficient synthesis of symmetric, unsymmetric and cyclic azo compounds.
Structurally Diverse Matrine‐Based Alkaloids with Anti‐inflammatory Effects from Sophora alopecuroides
Authors: Luo Ding , Chen Neng‐Hua , Wang Wen‐Zhi , Zhang Ji‐Hui , Li Can‐Jie , Zhuo Xue‐Fang , Tu Zhen‐Chao , Wu Zhong‐Nan , Fan Chun‐Lin , Zhang Hai‐Peng , Li Yao‐Lan , Wang Guo‐Cai , Zhang Yu‐Bo
Published: September 2021

Main observation and conclusion

A phytochemical investigation on the seeds of Sophora alopecuroides led to obtaining fourteen structurally diverse matrine‐based alkaloids (1—14), including eight new ones (1, 6, 8—12, 14). Notably, alopecuroide F (1) represents the first dimeric matrine‐type skeleton assembled via unprecedent C‐13–C‐12' connection. The new structures were determined through extensive spectroscopic data (UV, OR, HRESIMS, 1D, and 2D NMR), ECD calculations, and three instances, verified by X‐ray crystallography. Biologically, all alkaloids were evaluated for cytotoxicity against four human cancer cell lines (HepG2, A549, THP‐1, and MCF‐7) and anti‐inflammatory activities for two pro‐inflammatory cytokines (TNF‐α and IL‐6). Alopecuroide F (1) can inhibit TNF‐α and IL‐6 productions in a dose‐dependent manner, with IC50 values of 35.6 ± 0.5 and 41.7 ± 0.8 μmol/L, respectively.
Initial cancer treatment and survival in children, adolescents, and young adults with Hodgkin lymphoma: A population‐based study
Authors: Kahn Justine M. , Maguire Frances B. , Li Qian , Abrahão Renata , Flerlage Jamie E. , Alvarez Elysia , Keegan Theresa H. M.
Published: September 2021

Background

Hodgkin lymphoma (HL) is a treatable tumor affecting children, adolescents and young adults (AYAs; 15‐39 years old). Population‐based studies report worse survival for non‐White children and AYAs but have limited data on individual therapeutic exposures. This study examined overall and HL‐specific survival in a population‐based cohort of patients while adjusting for sociodemographic factors and treatment.

Methods

Data for 4807 patients younger than 40 years with HL (2007‐2017) were obtained from the California Cancer Registry. Individual treatment information was extracted from text fields; chemotherapy regimens were defined by standard approaches for pediatric and adult HL. Multivariable Cox models examined the influence of patient and treatment factors on survival.

Results

At a median follow‐up of 4.4 years, 95% of the patients were alive. Chemotherapy differed by age, with 70% of 22‐ to 39‐year‐olds and 41% of <22‐year‐olds receiving doxorubicin, bleomycin, vinblastine, and dacarbazine (P < .001). In multivariable models, older patients (22‐39 vs < 21 y; hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11‐2.10), Black (vs White patients); HR, 1.90; 95% CI, 1.25‐2.88), and Hispanic patients (HR, 1.45; 95% CI, 1.06‐1.99) experienced worse survival; among those < 21 y, Black race was associated with a 3.3‐fold increased risk of death (HR, 3.26; 95% CI, 1.43‐7.42).

Conclusions

In children and AYAs with HL, older age and non‐White race/ethnicity predicted worse survival after adjustments for treatment data. Further work is needed to identify the biological and nonbiological factors driving disparities in these at‐risk populations.
Strategies to improve diversity, equity, and inclusion in clinical trials
Authors: Kahn Justine M. , Gray Darrell M. , Oliveri Jill M. , Washington Chasity M. , DeGraffinreid Cecilia R. , Paskett Electra D.
Published: September 2021

There is a growing need for diversity, equity, and inclusion (DEI) in cancer care, particularly with respect to equal access and accrual to clinical trials. This commentary describe steps taken to address disparities in the authors' own clinical practice and proposes actions at the patient, provider, community, and institution levels to improve DEI in clinical trials.
Deciphering the minimal quantity of mouse primary cells to undergo nephrogenesis ex vivo
Authors: Rak‐Raszewska Aleksandra , Reint Ganna , Geiger Fabienne , Naillat Florence , Vainio Seppo J.
Published: September 2021

Background

Tissue organoids derived from primary cells have high potential for studying organ development and diseases in numerous organs. They recreate the morphological structure and mimic the functions of given organ while being compact in size, easy to produce, and suitable for use in various experimental setups.

Results

In this study we established the number of cells that form mouse kidney rudiments at E11.5, and generated renal organoids of various sizes from the mouse primary cells of the metanephric mesenchyme (MM). We investigated the ability of renal organoids to undergo nephrogenesis upon Wnt/ β‐catenin pathway—mediated tubule induction with a GSK‐3 inhibitor (BIO) or by initiation through the ureteric bud (UB). We found that 5000 cells of MM cells are necessary to successfully form renal organoids with well‐structured nephrons as judged by fluorescent microscopy, transmission electron microscopy (TEM), and quantitative Polymerase Chain Reaction (qPCR). These mouse organoids also recapitulated renal secretion function in the proximal tubules.

Conclusions

We show that a significant decrease of cells used to generate renal mouse organoids in a dissociation/re‐aggregation assay, does not interfere with development, and goes toward 3Rs. This enables generation of more experimental samples with one mouse litter, limiting the number of animals used for studies.
Integration of imaging and circulating biomarkers in heart failure: a consensus document by the Biomarkers and Imaging Study Groups of the Heart Failure Association of the European Society of Cardiology
Authors: Moura Brenda , Aimo Alberto , Al‐Mohammad Abdallah , Flammer Andreas , Barberis Vassilis , Bayes‐Genis Antoni , Brunner‐La Rocca Hans‐Peter , Fontes‐Carvalho Ricardo , Grapsa Julia , Hülsmann Martin , Ibrahim Nasrien , Knackstedt Christian , Januzzi James L. , Lapinskas Tomas , Sarrias Axel , Matskeplishvili Simon , Meijers Wouter C. , Messroghli Daniel , Mueller Christian , Pavo Noemi , Simonavičius Justas , Teske Arco J. , van Kimmenade Roland , Seferovic Petar , Coats Andrew J.S. , Emdin Michele , Richards A. Mark
Published: September 2021

Circulating biomarkers and imaging techniques provide independent and complementary information to guide management of heart failure (HF). This consensus document by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) presents current evidence‐based indications relevant to integration of imaging techniques and biomarkers in HF. The document first focuses on application of circulating biomarkers together with imaging findings, in the broad domains of screening, diagnosis, risk stratification, guidance of treatment and monitoring, and then discusses specific challenging settings. In each section we crystallize clinically relevant recommendations and identify directions for future research. The target readership of this document includes cardiologists, internal medicine specialists and other clinicians dealing with HF patients.
Application of first‐order finite similitude in structural mechanics and earthquake engineering
Authors: Atar Muhammed , Davey Keith , Darvizeh Rooholamin
Published: September 2021

An important experimental approach for the testing of earthquake‐resistant structures is scaled experimentation with experimental designs impacted upon by the similitude theory of dimensional analysis. Unfortunately, the type of similitude provided by dimensional analysis seldom applies to complex structures, which is particularly problematic when scaling ratios are large. The issue is one of scale effects where the behaviour of the scaled version of any full‐size structure can be markedly different. Recently however a new theory of scaling called finite similitude has emerged in the open literature that confirms that the similitude offered by dimensional analysis is just one of a countable infinite number of alternative possibilities. The new theory of scaling raises the possibility that buildings and structures can be designed and tested in new ways and this aspect is the focus of this paper. Similitude rules for single and two scaled experiments are examined to illustrate the benefits provided by alternative forms of similitude. The two types of similitude examined are termed zeroth order and first order finite similitude, which are shown to be two forms in an infinite number of alternative possibilities efficiently defined using a recursive relationship. The theory of scaling is founded on the metaphysical concept of space scaling yet provides the means to establish all scale dependencies for structural components and high‐rise steel buildings along with buildings equipped with nonlinear‐fluid viscous dampers for resisting earthquake loading conditions. It is shown through case‐studies of increasing complexity how the new theory can be applied to reconstruct full‐scale behaviours but also revealed are some of the limitations of the new approach.
Perspectives on being a field‐based geomorphologist during pregnancy and early motherhood
Authors: Lininger Katherine B. , Rowan Ann V. , Livers Bridget , Kramer Natalie , Ruiz‐Villanueva Virginia , Sendrowski Alicia , Burrough Sallie
Published: September 2021

Many geomorphologists who are mothers find it challenging to balance field research alongside pregnancy and caring for young children. We offer perspectives on the challenges to conducting fieldwork as mothers and possible solutions, as a means of promoting conversations and highlighting issues that are less commonly considered in field‐based geomorphic research. Although every mother's experience and needs are different, we discuss strategies for conducting fieldwork, addressing childcare issues, and dealing with financial considerations. We call for our community to support geomorphologists who are pregnant or caring for young children in carrying out fieldwork to help enhance the diversity of voices and perspectives within our discipline.
Technical, economic feasibility and sensitivity analysis of solar photovoltaic/battery energy storage off‐grid integrated renewable energy system
Authors: Chaurasia Ravi , Gairola Sanjay , Pal Yash
Published: September 2021

This paper aims to reduce LCOE (levelized cost of energy), NPC (net present cost), unmet load, and greenhouse gas emissions by utilizing an optimized solar photovoltaic (SPV)/battery energy storage (BES) off‐grid integrated renewable energy system configured with a 21‐kW SPV, 5707.8 kW BES, and a 12‐kW converter system. The LCOE is reduced to 14.73% of that obtained in the diesel generator (DG)‐only system by deploying the proposed energy system and to 28.61% of that obtained in the DG/battery energy system. The NPC is reduced to 14.78% of that DG and 28.70% of that DG/battery energy system. By sensitivity analysis, it is found that LCOE decreases with the increasing inflation rate and also with the decreasing discount rate. A performance compression analysis between the designed energy system and similar recent studies has also been presented. The proposed energy system reduces diesel consumption by at least 8113 L/year and total greenhouse gas emissions by at least 21 545 kg/year in the study area. Also, 13.9% of excess energy is produced per year at only 0.02% of the unmet load percentage. These outcomes are extremely relevant for making investments in policies for supplying electricity to a residential load in a low‐load profile area.
Macroeconomic conditions and health‐related outcomes in the United States: A metropolitan and micropolitan statistical area‐level analysis between 2004 and 2017
Authors: Peng Lizhong , Chen Jie , Guo Xiaohui
Published: September 2021

We study the relationship between macroeconomic conditions and health in the United States using data from the Behavioral Risk Factor Surveillance System between 2004 and 2017. Unlike many existing studies that use state or county as the level of aggregation, our analysis uses a sample of metropolitan and micropolitan statistical areas. Our results suggest strong associations between worsening macroeconomic conditions and reduced access to care and health insurance coverage. While we do not detect any robust relationships between business cycles and health outcomes in the general population, we do find consistent evidence of worse self‐reported health during economic downturns among minorities and less‐educated individuals. In addition, there is some suggestive evidence of countercyclicality of healthier lifestyle choices. However, the findings for health behavior outcomes are not robust to adjusting for multiple hypothesis testing.
Melanoma differentiation—Associated gene 5 protects against NASH in mice
Authors: Zhang Xin , Yang Hailong , Zeng Shan , Tian Song , Hu Sha , Yang Ling , Ma Tengfei , Liu Zhen , Wan Juan , Zhong Yiming , Li Hongliang
Published: September 2021

Background and Aims

NASH is a complicated disease characterized by hepatocyte steatosis, inflammation infiltration, and liver fibrosis. Accumulating evidence suggests that the innate immunity plays a key role in NASH progression. Here, we aimed to reveal the role of melanoma differentiation–associated gene 5 (MDA5, also known as Ifih1), a conventional innate immune regulator following viral infection, in the progression of NASH and investigate its underlying mechanism.

Approach and Results

We first examined the expression of MDA5 and found that MDA5 was markedly down‐regulated in the livers with NASH in human individuals and mice models. MDA5 overexpression significantly inhibits the free fatty acid–induced lipid accumulation and inflammation in hepatocyte in vitro, whereas MDA5 knockdown promotes hepatocyte lipotoxicity. Using hepatocyte‐specific Mda5 gene knockout and transgenic mice, we found that diet‐induced hepatic steatosis, inflammation, and liver fibrosis were markedly exacerbated by Mda5 deficiency but suppressed by Mda5 overexpression. Mechanistically, we found that the activation of apoptosis signal‐regulating kinase 1 (ASK1)–mitogen‐activated protein kinase pathway was significantly inhibited by MDA5 but enhanced by MDA5 deletion. We further validated that MDA5 directly interacted with ASK1 and suppressed its N‐terminal dimerization. Importantly, blockage of ASK1 with adenovirus‐expressing dominant negative ASK1 obviously reversed the lipid accumulation and ASK1 pathway activation when Mda5 was knocked out.

Conclusions

These data indicate that MDA5 is an essential suppressor in NASH. The findings support MDA5 as a regulator of ASK1 and a promising therapeutic target for NASH.
Numerical investigation on entropy generation in the dropwise condensation inside an inclined pipe
Authors: Zolfaghari Abbas , Aminian Ehsan , Saffari Hamid
Published: September 2021

In this paper, the entropy generation analysis in dropwise condensation in an inclined pipe is carried out. As the vapor passes through the inclined pipe, the flow of the droplets occurs due to the interfacial shear and gravity. Three distinct zones considered in the numerical study include the saturated vapor flowing in the axial direction, saturated liquid traveling through the bottom of the pipe, and the condensate droplet flowing on the inner side of the pipe wall. With the aim of achieving optimal geometrical conditions of the pipe and flow, the entropy generation was calculated for various cases. The results show that the minimum entropy generation of 0.0754 W·K−1 occurs in a configuration with a diameter of 9.5 mm and an inclination angle of 1°. Finally, the Bejan number, irreversibility distribution ratio, and variation according to the flow conditions were presented.
Intra‐annual variability of urban effects on streamflow
Authors: Diem Jeremy E. , Pangle Luke A. , Milligan Richard A. , Adams Ellis A.
Published: September 2021

While considerable research has established the impacts of urbanization on streamflow, there has been little emphasis on how intra‐annual variations in streamflow can deepen the understanding of hydrological processes in urban watersheds. This study fills this critical research gap by examining, at the monthly scale, correlations between land‐cover and streamflow, differences in streamflow metrics between urban and rural watersheds, and the potential for the inflow and infiltration (I&I) of extraneous water into sewers to reduce streamflow. We use data from 90 watersheds in the Atlanta, GA region over the 2013–2019 period to accomplish our objectives. Similar to other urban areas in temperate climates, Atlanta has a soil‐water surplus in winter and a soil‐water deficit in summer. Our results show urban watersheds have less streamflow seasonality than do rural watersheds. Compared to rural watersheds, urban watersheds have a much larger frequency of high‐flow days during July–October. This is caused by increased impervious cover decreasing the importance of antecedent soil moisture in producing runoff. Urban watersheds have lower baseflows than rural watersheds during December–April but have baseflows equal to or larger than baseflows in rural watersheds during July–October. Intra‐annual variations in effluent data from wastewater treatment plants provide evidence that I&I is a major cause of the relatively low baseflows during December–April. The relatively high baseflows in urban watersheds during July–October are likely caused by reduced evapotranspiration and the inflow of municipal water. The above seasonal aspects of urban effects on streamflow should be applicable to most urban watersheds with temperate climates.
The experience of diagnostic radiography students during the early stages of the COVID‐19 pandemic – a cross‐sectional study
Authors: Lawson Jones Gaynor , York Helen , Lawal Olanrewaju , Cherrill Richard , Mercer Sarah , McCarthy Zoe
Published: September 2021

Introduction

The rationale for this study was to ascertain the impact of the COVID‐19 pandemic on Undergraduate B.Sc (Hons) Diagnostic Radiography students at the University of Hertfordshire in the UK. This would provide an ideal opportunity for students to reflect on their experience and indicate if they required additional support from the University.

Methods

An online anonymous cross‐sectional survey was deployed to all year groups (n = 283) during the first nationwide lockdown in May 2020, eliciting qualitative responses on questions about the effect of the pandemic; emotions experienced; support required and consideration of their choice of a career in the health sector.

Results

Two hundred and one students responded to the survey, with many having experienced the illness or loss of a loved one. Trying to balance family commitments and study was a concern to some students, as well as struggling with the financial burden of job losses or furlough. Many students commented that educational support was a requirement with the move to online teaching and assessment. The main focus of student responses was the emotions that they had experienced, many of which were negative. Anxiety and fear were commonly expressed feelings, along with sadness and feelings of isolation. A small number of students reported feeling grateful, happy and relieved. An overwhelming majority of respondents commented that they were proud to be healthcare students and they were resolute in wanting to continue the course and join the frontline of the NHS workforce.

Conclusion

Some students have been deeply affected by their experiences of the pandemic, and University support mechanisms should be refined to better assist with their ongoing challenges.
Diagnostic accuracy of severe periodontitis case definitions: Comparison of the CDC/AAP, EFP/AAP, and CPI criteria
Authors: Brito Liana F. , Taboza Zuila A. , Silveira Virginia R. , Teixeira Ana K. , Rego Rodrigo O.
Published: September 2021

Background

This cross‐sectional study aimed to evaluate the diagnostic accuracy of severe periodontitis by three different case definitions.

Methods

Patients aged >35 years (n = 243, mean age = 47.8 ± 9.3 years) were evaluated by periodontal examinations and classified in patients with severe periodontitis according to the case definition proposed by the Centers for Disease Control and Prevention (CDC) in collaboration with the American Academy of Periodontology (AAP)—CDC/AAP, the new periodontal disease classification proposed jointly by the AAP and the European Federation of Periodontology (EFP/AAP), and the Community Periodontal Index (CPI). The primary outcome was to compare the diagnostic accuracy of severe periodontitis between the three case definitions. Sensitivity (SS), specificity (SP), and area under the receiver operating characteristic (ROC) curve were used to analyze the accuracy.

Results

The proportion of subjects presenting the most severe definitions of each classification was: severe periodontitis (CDC/AAP) = 47.3%, type III and IV periodontitis (EFP/AAP) = 43.2% and CPI code 4 = 44.4%. When comparing the CDC/AAP case definitions with the EFP/AAP classification, SS, SP, and ROC of 81.7%, 91.4%, and 0.866 (CI, 95%: 0.816 to 0.916), respectively, were obtained. Similarly, when comparing CDC/AAP to CPI code 4, SS, SP, and ROC of 81.7%, 89.1%, and 0.854 (CI, 95%: 0.802 to 0.906), respectively, were obtained. When type III and IV periodontitis (EFP/AAP) was compared with CPI code 4, the values were 92.4%, 92%, and 0.922 (CI, 95%: 0.883 to 0.961), respectively.

Conclusions

The EFP/AAP classification and the CPI demonstrated high diagnostic accuracy with the CDC/AAP case definition to diagnose severe periodontitis.
A 3‐Decade, Single‐Center Experience of Liver Transplantation for Cholangiocarcinoma: Impact of Era, Tumor Size, Location, and Neoadjuvant Therapy
Authors: Ito Takahiro , Butler James R. , Noguchi Daisuke , Ha Minah , Aziz Antony , Agopian Vatche G. , DiNorcia Joseph , Yersiz Hasan , Farmer Douglas G. , Busuttil Ronald W. , Hong Johnny C. , Kaldas Fady M.
Published: September 2021

Liver transplantation (LT) for cholangiocarcinoma (CCA) remains limited to a small number of centers. Although the role of neoadjuvant therapy (NAT) has been explored over time, an in‐depth analysis of NAT strategies remains limited. Furthermore, controversy exists regarding acceptable tumor size during patient selection for LT. This study explores the impact of era, tumor size, and NAT strategy on LT outcomes for CCA. We conducted a retrospective review of 53 patients with CCA treated with LT from 1985 to 2019; 19 hilar CCA (hCCA) and 30 intrahepatic CCA (iCCA) were included. The relative contributions of varying NAT (neoadjuvant chemotherapy [NAC], neoadjuvant local therapy [NALT], and combined NAC and NALT [NACLT]) as well as the implication of tumor size and era were analyzed. The primary endpoint was overall survival (OS). Compared with the old era (1985‐2007), 5‐year OS in patients who underwent LT in the recent era (2008‐2019) showed a superior trend. The 5‐year OS from initial treatment in patients receiving NACLT for hCCA and iCCA were 88% and 100% versus 9% and 41% in patients without it, respectively (P = 0.01 for hCCA; P = 0.02 for iCCA), whereas NAC or NALT alone did not show significant differences in OS versus no NAT (P > 0.05). Although 33 patients had large‐size tumors (hCCA ≥ 30 mm, n = 12, or iCCA ≥ 50 mm, n = 21), tumor size had no impact on survival outcomes. Outcomes of LT for CCA seem to have improved over time. Multimodal NAT is associated with improved survival in LT for both iCCA and hCCA regardless of tumor size.