bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences in multimorbidity and polypharmacy trends: A repeated cross-sectional study of older adults in Ontario, Canada
Authors: Maxwell Colleen J. , Mondor Luke , Pefoyo Koné Anna J. , Hogan David B. , Wodchis Walter P. 
Published: April 2021

Background
Multimorbidity is increasing among older adults, but the impact of these recent trends on the extent and complexity of polypharmacy and possible variation by sex remains unknown. We examined sex differences in multimorbidity, polypharmacy (5+ medications) and hyper-polypharmacy (10+ medications) in 2003 vs 2016, and the interactive associations between age, multimorbidity level, and time on polypharmacy measures.

Methods and findings
We employed a repeated cross-sectional study design with linked health administrative databases for all persons aged ≥66 years eligible for health insurance in Ontario, Canada at the two index dates. Descriptive analyses and multivariable logistic regression models were conducted; models included interaction terms between age, multimorbidity level, and time period to estimate polypharmacy and hyper-polypharmacy probabilities, risk differences and risk ratios for 2016 vs 2003. Multimorbidity, polypharmacy and hyper-polypharmacy increased significantly over the 13 years. At both index dates prevalence estimates for all three were higher in women, but a greater absolute increase in polypharmacy over time was observed in men (6.6% [from 55.7% to 62.3%] vs 0.9% [64.2%-65.1%] for women) though absolute increases in multimorbidity were similar for men and women (6.9% [72.5%-79.4%] vs 6.2% [75.9%-82.1%], respectively). Model findings showed that polypharmacy decreased over time among women aged < 90 years (especially for younger ages and those with fewer conditions), whereas it increased among men at all ages and multimorbidity levels (with larger absolute increases typically at older ages and among those with 4 or fewer conditions).

Conclusions
There are sex and age differences in the impact of increasing chronic disease burden on changes in measures of multiple medication use among older adults. Though the drivers and health consequences of these trends warrant further investigation, the findings support the heterogeneity and complexity in the evolving association between multimorbidity and polypharmacy measures in older populations.
Utility of hospitalization for elderly individuals affected by COVID-19
Authors: Costantino Giorgio , Solbiati Monica , Elli Silvia , Paganuzzi Marco , Massabò Didi , Montano Nicola , Mancarella Marta , Cortellaro Francesca , Cataudella Emanuela , Bellone Andrea , Capsoni Nicolò , Bertolini Guido , Nattino Giovanni , Casazza Giovanni 
Published: April 2021

Background
During the COVID-19 pandemic, the number of individuals needing hospital admission has sometimes exceeded the availability of hospital beds. Since hospitalization can have detrimental effects on older individuals, preference has been given to younger patients. The aim of this study was to assess the utility of hospitalization for elderly affected by COVID-19. We hypothesized that their mortality decreases when there is greater access to hospitals.

Methods
This study examined 1902 COVID-19 patients consecutively admitted to three large hospitals in Milan, Italy. Overall mortality data for Milan from the same period was retrieved. Based on emergency department (ED) data, both peak and off-peak phases were identified. The percentage of elderly patients admitted to EDs during these two phases were compared by calculating the standardized mortality ratio (SMR) of the individuals younger than, versus older than, 80 years.

Results
The median age of the patients hospitalized during the peak phase was lower than the median age during the off-peak phase (64 vs. 75 years, respectively; p <0.001). However, while the SMR for the younger patients was lower during the off-peak phase (1.98, 95% CI: 1.72–2.29 versus 1.40, 95% CI: 1.25–1.58, respectively), the SMR was similar between both phases for the elderly patients (2.28, 95% CI: 2.07–2.52 versus 2.48, 95% CI: 2.32–2.65, respectively).

Conclusions
Greater access to hospitals during an off-peak phase did not affect the mortality rate of COVID-19-positive elderly patients in Milan. This finding, if confirmed in other settings, should influence future decisions regarding resource management of health care organizations.
Benefit versus risk of chromosomal microarray analysis performed in pregnancies with normal and positive prenatal screening results: A retrospective study
Authors: Moshonov Rami , Hod Keren , Azaria Bella , Abadi-Korek Ifat , Berger Rachel , Shohat Mordechai 
Published: April 2021

BackgroundMost studies on chromosomal microarray analysis (CMA) and amniocentesis risks have not evaluated pregnancies with low risk for genetic diseases; therefore, the efficacy and safety of CMA and amniocentesis in this population are unclear. This study aimed to examine the benefits and risks of prenatal genetic diagnostic tests in pregnancies having low risk for chromosomal diseases.Methods and findingsIn this retrospective study, we used clinical data from a large database of 30,830 singleton pregnancies at gestational age 16–23 weeks who underwent amniocentesis for karyotyping with or without CMA. We collected socio-demographic, medical and obstetric information, along with prenatal screening, CMA and karyotyping results. Fetal loss events were also analysed. CMA was performed in 5,837 pregnancies with normal karyotype (CMA cohort). In this cohort, 4,174 women had normal prenatal screening results and the risk for identifying genetic abnormalities with >10% risk for intellectual disability by CMA was 1:102, with no significant difference between maternal age groups. The overall post-amniocentesis fetal loss rate was 1:1,401 for the entire cohort (n = 30,830) and 1:1,945 for the CMA cohort (n = 5,837). The main limitation of this study is the relatively short follow-up of 3 weeks, which may not have been sufficient for detecting all fetal loss events.ConclusionThe low risk for post-amniocentesis fetal loss, compared to the rate of severe genetic abnormalities detected by CMA, suggests that even pregnant women with normal prenatal screening results should consider amniocentesis with CMA.
Felicidad y educación: déficits científicos y sesgos ideológicos de la “educación positiva”
Authors: Cabanas Díaz Edgar , González-Lamas Jara 
Published: April 2021

El interés generado por la “educación positiva” ha crecido de forma exponencial en las últimas dos décadas. Presentado como un nuevo movimiento científico llamado a sustituir enfoques tradicionales o remediales en materia de intervención educativa, el argumento principal del movimiento es que la felicidad y la enseñanza de habilidades positivas son factores fundamentales para prevenir problemas de salud mental, mejorar el aprendizaje o promover el rendimiento escolar. En paralelo a este crecimiento, las críticas dirigidas a la educación positiva han sido también crecientes y numerosas, destacando no sólo aquellas procedentes de terceros, sino las procedentes desde el propio movimiento. Todas estas críticas ponen en duda la solidez y la utilidad de la educación positiva. El objetivo de este trabajo es ofrecer una mirada panorámica e integradora de estas críticas con el fin de facilitar una mayor comprensión de los principales problemas y limitaciones del movimiento. Estos problemas se organizan en torno a dos bloques temáticos principales: científicos e ideológicos. Dentro de los déficits científicos, el trabajo destaca la ausencia de un marco teórico general y la falta de evidencia acumulada, las notables limitaciones conceptuales y metodológicas en torno a constructos principales y la moderada eficacia, así como la baja generalizabilidad de sus intervenciones clave. Dentro del bloque ideológico, se abordan los principales sesgos y asunciones que subyacen el movimiento, tales como el marcado carácter individualista, descontextualizado y universalista del mismo. Para terminar, el artículo concluye con una breve reflexión en torno a la educación positiva y sus implicaciones en el ámbito de la educación.
Effect of Diameter and Number of Hepatocellular Carcinomas on Survival After Resection, Transarterial Chemoembolization, and Ablation
Authors: Kawaguchi Yoshikuni , Hasegawa Kiyoshi , Hagiwara Yasuhiro , De Bellis Mario , Famularo Simone , Panettieri Elena , Matsuyama Yutaka , Tateishi Ryosuke , Ichikawa Tomoaki , Kokudo Takashi , Izumi Namiki , Kubo Shoji , Sakamoto Michiie , Shiina Shuichiro , Takayama Tadatoshi , Nakashima Osamu , Murakami Takamichi , Vauthey Jean-Nicolas , Giuliante Felice , De Carlis Luciano , Romano Fabrizio , Ruzzenente Andrea , Guglielmi Alfredo , Kudo Masatoshi , Kokudo Norihiro 
Published: April 2021

INTRODUCTION:
Most studies predicting survival after resection, transarterial chemoembolization (TACE), and ablation analyzed diameter and number of hepatocellular carcinomas (HCCs) as dichotomous variables, resulting in an underestimation of risk variation. We aimed to develop and validate a new prognostic model for patients with HCC using largest diameter and number of HCCs as continuous variables.

METHODS:
The prognostic model was developed using data from patients undergoing resection, TACE, and ablation in 645 Japanese institutions. The model results were shown after balanced using the inverse probability of treatment-weighted analysis and were externally validated in an international multi-institution cohort.

RESULTS:
Of 77,268 patients, 43,904 patients, including 15,313 (34.9%) undergoing liver resection, 13,375 (30.5%) undergoing TACE, and 15,216 (34.7%) undergoing ablation, met the inclusion criteria. Our model (http://www.u-tokyo-hbp-transplant-surgery.jp/about/calculation.html) showed that the 5-year overall survival (OS) in patients with HCC undergoing these procedures decreased with progressive incremental increases in diameter and number of HCCs. For patients undergoing resection, the inverse probability of treatment-weighted-adjusted 5-year OS probabilities were 10%–20% higher compared with patients undergoing TACE for 1–6 HCC lesions <10 cm and were also 10%–20% higher compared with patients undergoing ablation when the HCC diameter was 2–3 cm. For patients undergoing resection and TACE, the model performed well in the external cohort.

DISCUSSION:
Our novel prognostic model performed well in predicting OS after resection and TACE for HCC and demonstrated that resection may have a survival benefit over TACE and ablation based on the diameter and number of HCCs.
Digital Watermarking using Grasshopper Optimization Algorithm
Authors: Sharma Satender , Chauhan Usha , Khanam Ruqaiya , Singh Krishna Kant 
Published: April 2021

Abstract
The advancement in computer science technology has led to some serious concerns about the piracy and copyright of digital content. Digital watermarking technique is widely used for copyright protection and other similar applications. In this paper, a technique for digital watermarking based on Discrete Cosine Transform (DCT), Discrete Wavelet Transform (DWT), and Grasshopper Optimization Algorithm (GOA) is proposed. The method computes the DWT of the cover image to obtain the sub-components of the image. The subcomponent is converted to frequency domain using DCT. The challenge is to find the optimal scaling factor to be used for watermarking. The authors have designed a GOA based technique that finds the optimized scaling factor and the coefficient for embedding the watermark. GOA makes the watermark undetectable and is invisible in the cover image. The watermark image is embedded in the cover image using these coefficients. The extraction of watermark from the cover image is done by using inverse DCT and DWT. The proposed method is compared with the other state of the art methods. The effectiveness of the proposed method is computed using Peak Signal to Noise Ratio (PSNR), Normalized Cross Correlation (NCC) and Image Fidelity (IF). The proposed method outperforms the other methods and can be effectively used for practical digital watermarking.
Investigation of the prevalence of cardiovascular risk factors in obese patients diagnosed with metabolic syndrome in childhood and examination of left ventricular function by echocardiography
Authors: Özden Güzin , Kibar Gül Ayşe Esin , Mengen Eda , Ucaktürk Ahmet , Gürsu Hazım Alper , Çetin İbrahim İlker , Kızılgün Murat 
Published: April 2021

Abstract

Objectives
The objective of this study is to investigate the cardiovascular risk factors associated with metabolic syndrome (MetS), which is increasingly becoming prevalent in childhood obesity.

Methods
A total of 113 patients, 76 of whom were between the ages of 10 and 17 (mean age: 14.5 ± 1.8 years) and diagnosed with obesity (30 non-MetS and 46 MetS using IDF) and 37 of whom constituted the control group, participated in the study. Echocardiographic examination and atherogenicity parameters (Atherogenic index of plasma [AIP: logTG/HDL], total cholesterol/HDL, and TG/HDL ratio and non-HDL) were evaluated.

Results
The most common component accompanying obese MetS was found to be hypertension and low HDL. While obesity duration, body mass index (BMI), blood pressure, fasting insulin, insulin resistance, atherogenicity parameters were determined to be significantly higher in the obese-MetS group. Echocardiography showed that while the thickness, volume, and diameter of LV end-diastolic wall, left ventricular mass (LVM), LVM index (LVMI g/m2) and relative wall thickness (RWT) were significantly high in the MetS group, however, mitral E/A ratio was significantly lower (p<0.05). Change in LV geometry consistent with concentric remodeling (increased RWT, normal LVMI) was visible in obese groups. LVM were positively significantly related to BMI, waist circumference, insulin resistance, blood pressure, LDL level, and negative to mitral E/A ratio. In the obese-MetS group, LVMI was positively correlated to office systolic BP, left atrium end-diastolic volume/index.

Conclusions
LVMI and atherogenicity parameters that were found to be significantly higher in obese MetS exhibit increased cardiovascular risk in childhood.
Local and CNS-Wide Astrocyte Intracellular Calcium Signaling AttenuationIn Vivowith CalExfloxMice
Authors: Yu Xinzhu , Moye Stefanie L. , Khakh Baljit S. 
Published: April 2021

Astrocytes exist throughout the CNS and affect neural circuits and behavior through intracellular Ca2+signaling. Studying the function(s) of astrocyte Ca2+signaling has proven difficult because of the paucity of tools to achieve selective attenuation. Based on recent studies, we generated and used male and female knock-in mice for Cre-dependent expression of mCherry-tagged hPMCA2w/b to attenuate astrocyte Ca2+signaling in genetically defined cellsin vivo(CalExfloxmice forCalciumExtrusion). We characterized CalExfloxmice following local AAV-Cre microinjections into the striatum and found reduced astrocyte Ca2+signaling (∼90%) accompanied with repetitive self-grooming behavior. We also crossed CalExfloxmice to astrocyte-specificAldh1l1-Cre/ERT2 mice to achieve inducible global CNS-wide Ca2+signaling attenuation. Within 6 d of induction in the bigenic mice, we observed significantly altered ambulation in the open field, disrupted motor coordination and gait, and premature lethality. Furthermore, with histologic, imaging, and transcriptomic analyses, we identified cellular and molecular alterations in the cerebellum following mCherry-tagged hPMCA2w/b expression. Our data show that expression of mCherry-tagged hPMCA2w/b with CalExfloxmice throughout the CNS resulted in substantial attenuation of astrocyte Ca2+signaling and significant behavioral alterations in adult mice. We interpreted these findings candidly in relation to the ability of CalEx to attenuate astrocyte Ca2+signaling, with regards to additional mechanistic interpretations of the data, and their relation to past studies that reduced astrocyte Ca2+signaling throughout the CNS. The data and resources provide complementary ways to interrogate the function(s) of astrocytes in multiple experimental scenarios.SIGNIFICANCE STATEMENTAstrocytes represent a significant fraction of all brain cells and tile the entire central nervous system. Unlike neurons, astrocytes lack propagated electrical signals. Instead, astrocytes are proposed to use diverse and dynamic intracellular Ca2+signals to communicate with other cells. An open question concerns if and how astrocyte Ca2+signaling regulates behavior in adult mice. We approached this problem by generating a new transgenic mouse line to achieve inducible astrocyte Ca2+signaling attenuationin vivo. We report our data with this mouse line and we interpret the findings candidly in relation to past studies and within the framework of different mechanistic interpretations.
Brain Coding of Social Network Structure
Authors: Peer Michael , Hayman Mordechai , Tamir Bar , Arzy Shahar 
Published: April 2021

Humans have large social networks, with hundreds of interacting individuals. How does the brain represent the complex connectivity structure of these networks? Here we used social media (Facebook) data to objectively map participants' real-life social networks. We then used representational similarity analysis (RSA) of functional magnetic resonance imaging (fMRI) activity patterns to investigate the neural coding of these social networks as participants reflected on each individual. We found coding of social network distances in the default-mode network (medial prefrontal, medial parietal, and lateral parietal cortices). When using partial correlation RSA to control for other factors that can be correlated to social distance (personal affiliation, personality traits. and visual appearance, as subjectively rated by the participants), we found that social network distance information was uniquely coded in the retrosplenial complex, a region involved in spatial processing. In contrast, information on individuals' personal affiliation to the participants and personality traits was found in the medial parietal and prefrontal cortices, respectively. These findings demonstrate a cortical division between representations of non-self-referenced (allocentric) social network structure, self-referenced (egocentric) social distance, and trait-based social knowledge.SIGNIFICANCE STATEMENTEach of us has a social network composed of hundreds of individuals, with different characteristics and different relations among them. How does our brain represent this complexity? To find out, we mapped participants' social connections using Facebook data and then asked them to think about individuals from their network while undergoing functional MRI scanning. We found that the position of individuals within the social network, as well as their affiliation to the participant, are mapped in the retrosplenial complex, a region involved in spatial processing. Individuals' personality traits were coded in another region, the medial prefrontal cortex. Our findings demonstrate a neural dissociation among different aspects of social knowledge and suggest a link between spatial and social cognitive mapping.
Selective degradation of synthetic polymers through enzymes immobilized on nanocarriers
Authors: Krakor Eva , Gessner Isabel , Wilhelm Michael , Brune Veronika , Hohnsen Johannes , Frenzen Lars , Mathur Sanjay 
Published: April 2021

AbstractIn order to develop new sustainable and reusable concepts for the degradation of omnipresent industrial plastics, immobilization of (bio)catalysts on nanocarriers offers unique opportunities for selective depolymerization and catalyst recovery. In this study, enzymes (lipase and cutinase) were covalently immobilized on carrier nanoparticles (SiO2and Fe3O4@SiO2) through 3-(aminopropyl)trimethoxysilane and glutaraldehyde linkers forming a stable bond to enzyme molecules. The presence of enzymes on the surface was confirmed by zeta potential and XPS measurements, while their degradation activity and long-term stability of up to 144 h was demonstrated by the conversion of 4-nitrophenyl acetate to 4-nitrophenol. Furthermore, enzymatic decomposition (hydrolysis/oxidation) of electrospun polycaprolactone fiber mats was verified through morphological (SEM) and weight loss studies, which evidently showed a change in the fiber morphology due to enzymatic degradation and accordingly a weight loss.Graphic abstract
The Molecular Basis of Familial Hemolytic Uremic Syndrome
Authors: CAPRIOLI JESSICA , BETTINAGLIO PAOLA , ZIPFEL PETER F. , AMADEI BARBARA , DAINA ERICA , GAMBA SARA , SKERKA CHRISTINE , MARZILIANO NICOLA , REMUZZI GIUSEPPE , NORIS MARINA 
Published: April 2021

Abstract.
The aim of the present study was to clarify whether factor H mutations were involved in genetic predisposition to hemolytic uremic syndrome, by performing linkage and mutation studies in a large number of patients from those referred to the Italian Registry for Recurrent and Familial HUS/TTP. PCR and Western blot analyses were conducted to characterize the biochemical consequences of the mutations. Five mutations in the factor H gene were identified. Three, identified in two families and in a sporadic case, are heterozygous point mutations within the most C-terminal short consensus repeat 20 (SCR20) of factor H, resulting in single amino acid substitutions. The other two mutations introduce premature stop codons that interrupt the translation of factor H. A heterozygous nonsense mutation was identified in SCR8 in one family, and a homozygous 24-bp deletion within SCR20 was identified in a Bedouin family with a recessive mode of inheritance. Reverse transcription-PCR analysis of cDNA from peripheral blood leukocytes from the Bedouin family showed that the deletion lowered factor H mRNA levels. Although heterozygous mutations were associated with normal factor H levels and incomplete penetrance of the disease, the homozygous mutation in the Bedouin family resulted in severe reduction of factor H levels accompanied by very early disease onset. These data provide compelling molecular evidence that genetically determined deficiencies in factor H are involved in both autosomal-dominant and autosomal-recessive hemolytic uremic syndrome and identify SCR20 as a hot spot for mutations in the disease. The mutations identified here give an important hint to the relevance of the C-terminus of factor H in the control of the alternative complement activation pathway.
Cardiovascular Risk Factors in Renal Transplant Patients
Authors: LIGTENBERG GERRY , HENÉ RONALD J. , BLANKESTIJN PETER J. , KOOMANS HEIN A. 
Published: April 2021

Abstract.
The hypertensive and hyperlipidemic effects of cyclosporin A (CsA) may contribute to the high cardiovascular morbidity in renal transplant patients and to the development of chronic transplant nephropathy. Tacrolimus is reported to have less effect on BP and lipids, but steroids, other drugs, and renal function may confound this. This study assessed 24-h BP and lipid profile in stable renal transplant recipients (n = 17) while they were receiving CsA, after 4 wk of receiving tacrolimus, and again after 4 wk of receiving CsA. Antihypertensives were stopped at least 3 wk before. A few patients used low-dose steroids and lipid-lowering drugs, which were not changed during the study. Mean daytime BP decreased from 149 ± 12 and 95 ± 8 mmHg to 138 ± 13 and 87 ± 9 mmHg (P < 0.001) after patients were switched to tacrolimus. Mean nighttime BP also decreased, from 140 ± 12/86 ± 7 mmHg to 132 ± 17/79 ± 10 mmHg (P < 0.05). Total and low-density lipoprotein cholesterol decreased from 6.1 ± 0.7 and 3.84 ± 0.79 mmol/L to 5.1 ± 0.8 and 2.98 ± 0.75 mmol/L (P < 0.001). Return to CsA caused an increase in BP and cholesterol to values similar as during the first CsA period. The conclusion is that tacrolimus has fewer unfavorable effects on BP and lipids than does CsA. Elective conversion from CsA to tacrolimus in stable renal transplant recipients may lead to attenuation of cardiovascular morbidity and chronic transplant nephropathy in the long term.