bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-definition transcranial direct current stimulation enhances network segregation during spatial navigation in mild cognitive impairment
Authors: Iordan Alexandru D , Ryan Shannon , Tyszkowski Troy , Peltier Scott J , Rahman-Filipiak Annalise , Hampstead Benjamin M 
Published: January 2022

Abstract
Spatial navigation is essential for everyday life and relies on complex network-level interactions. Recent evidence suggests that transcranial direct current stimulation (tDCS) can influence the activity of large-scale functional brain networks. We characterized brain-wide changes in functional network segregation (i.e. the balance of within vs. between-network connectivity strength) induced by high-definition (HD) tDCS in older adults with mild cognitive impairment (MCI) during virtual spatial navigation. Twenty patients with MCI and 22 cognitively intact older adults (healthy controls—HC) underwent functional magnetic resonance imaging following two counterbalanced HD-tDCS sessions (one active, one sham) that targeted the right parietal cortex (center anode at P2) and delivered 2 mA for 20 min. Compared to HC, MCI patients showed lower brain-wide network segregation following sham HD-tDCS. However, following active HD-tDCS, MCI patients’ network segregation increased to levels similar to those in HC, suggesting functional normalization. Follow-up analyses indicated that the increase in network segregation for MCI patients was driven by HD-tDCS effects on the “high-level”/association brain networks, in particular the dorsal-attention and default-mode networks. HD-tDCS over the right parietal cortex may normalize the segregation/integration balance of association networks during spatial navigation in MCI patients, highlighting its potential to restore brain activity in Alzheimer’s disease.
Detecting, preventing and treating non-adherence to immunosuppression after kidney transplantation
Authors: Gandolfini Ilaria , Palmisano Alessandra , Fiaccadori Enrico , Cravedi Paolo , Maggiore Umberto 
Published: January 2022

ABSTRACT
Medication non-adherence (MNA) is a major issue in kidney transplantation and it is associated with increased risk of rejection, allograft loss, patients’ death and higher healthcare costs. Despite its crucial importance, it is still unclear what are the best strategies to diagnose, prevent and treat MNA. MNA can be intentional (deliberate refusal to take the medication as prescribed) or unintentional (non-deliberate missing the prescribed medication). Its diagnosis may rely on direct methods, aiming at measuring drug ingestions, or indirect methods that analyse the habits of patients to adhere to correct drug dose (taking adherence) and interval (time adherence). Identifying individual risk factors for MNA may provide the basis for a personalized approach to the treatment of MNA. Randomized control trials performed so far have tested a combination of strategies, such as enhancing medication adherence through the commitment of healthcare personnel involved in drug distribution, the use of electronic reminders, therapy simplification or various multidisciplinary approaches to maximize the correction of individual risk factors. Although most of these approaches reduced MNA in the short-term, the long-term effects on MNA and, more importantly, on clinical outcomes remain unclear. In this review, we provide a critical appraisal of traditional and newer methods for detecting, preventing and treating non-adherence to immunosuppression after kidney transplantation from the perspective of the practising physician.
phytochemdb: a platform for virtual screening and computer-aided drug designing
Authors: Mahmud Shafi , Paul Gobindo Kumar , Biswas Suvro , Kazi Taheruzzaman , Mahbub Shafquat , Mita Mohasana Akter , Afrose Shamima , Islam Ariful , Ahaduzzaman Sheikh , Hasan Md. Robiul , Shimu Mst. Sharmin Sultana , Promi Maria Meha , Shehab Mobasshir Noor , Rahman Ekhtiar , Sujon Khaled Mahmud , Alom Md. Wasim , Modak Anik , Zaman Shahriar , Uddin Md. Salah , Emran Talha Bin , Islam Md. Sayeedul , Saleh Md. Abu 
Published: January 2022

Abstract
The phytochemicals of medicinal plants are regarded as a rich source of diverse chemical spaces that have been used as supplements and alternative medicines in the millennium. Even in this era of combinatorial chemical drugs, phytomedicines account for a large share of the statistics of newly approved drugs. In the field of computational aided and rational drug design, there is an urgent need to develop and build a useful phytochemical database management system with a user-friendly interface that allows proper data storage, retrieval and management. We showed ‘phytochemdb’, a manually managed database that compiles 525 plants and their corresponding 8093 phytochemicals, aiming to incorporate the activities of phytochemicals from medicinal plants. The database collects molecular formula, three-dimensional/two-dimensional structure, canonical SMILES, molecular weight, no. of heavy atoms, no. of aromatic heavy atoms, fraction Csp3, no. of rotatable bonds, no. of H-bond acceptors, no. of H-bond donors, molar refractivity, topological polar surface area, gastrointestinal absorption, Blood–Brain Barrier (BBB) permeant, P-gp substrate, CYP1A2 inhibitor, CYP2C19 inhibitor, CYP2C9 inhibitor, CYP2D6 inhibitor, CYP3A4 inhibitor, Log Kp, Ghose, Veber, Egan, Muegge, bioavailability scores, pan-assay interference compounds, Brenk, Leadlikeness, synthetic accessibility, iLOGP and Lipinski rule of five with the number of violations for each compound. It provides open contribution functions for the researchers who screen phytochemicals in the laboratory and have released their data. ‘phytochemdb’ is a comprehensive database that gathers most of the information about medicinal plants in one platform, which is considered to be very beneficial to the work of researchers on medicinal plants. ‘phytochemdb’ is available for free at https://phytochemdb.com/.
Tricuspid regurgitation: recent advances in understanding pathophysiology, severity grading and outcome
Authors: Hahn Rebecca T , Badano Luigi P , Bartko Philipp E , Muraru Denisa , Maisano Francesco , Zamorano Jose L , Donal Erwan 
Published: January 2022

Abstract
Heightened interest in tricuspid regurgitation (TR) stems from the consistent association of mortality with greater severity of TR, and a low use of surgical solutions in the setting of high in-hospital mortality attributed to the late presentation of the disease. The delay in intervention is likely related to a limited understanding of the valvular/ventricular anatomy and disease pathophysiology, along with an underestimation of TR severity by standard imaging modalities. With the rapid development of transcatheter solutions which have shown early safety and efficacy, there is a growing need to understand and accurately diagnose the valvular disease process in order to determine appropriate management solutions. The current review will describe both normal and pathologic tricuspid valvular anatomy, the classification of these anatomic substrates of TR, the strengths and limitations of the current guidelines-recommended multi-parametric echocardiographic approach and the role of multi-modality imaging, as well as the role of transcatheter device therapy in the management of the disease.
The Brides of Boko Haram: Economic Shocks, Marriage Practices, and Insurgency in Nigeria
Authors: Rexer Jonah M 
Published: January 2022

AbstractMarriage markets in rural Nigeria are characterised by bride price and polygamy. These customs may diminish marriage prospects for young men, causing them to join militant groups. Using an instrumental variables strategy, I find that marriage inequality increases civil conflict in the Boko Haram insurgency. To generate exogenous shocks to the marriage market, I exploit the fact that young women delay marriage in response to favourable pre-marital economic conditions, which increases marriage inequality primarily in polygamous villages. The same shocks that increase marriage inequality and extremist violence also lead women to marry fewer and richer husbands, generate higher average marriage expenditures, and increase insurgent abductions. The results shed light on the marriage market as an important driver of violent extremism.
What kind of EU fiscal capacity? Evidence from a randomized survey experiment in five European countries in times of corona
Authors: Beetsma Roel , Burgoon Brian , Nicoli Francesco , de Ruijter Anniek , Vandenbroucke Frank 
Published: January 2022

Abstract
Based on a conjoint survey experiment, we explore the support among European citizens for a European Union (EU) budgetary assistance instrument to combat adverse temporary or permanent economic shocks hitting Member States. Suitably designed, there is substantial support for such an EU instrument generally and across the sample countries. Support is broader when budgetary support is conditional on debt reduction in good times and on monies being spent in specific policy areas, in particular healthcare and education. Support also increases when there is a role for the European Commission in terms of monitoring and providing guidance. However, there is little support for policy packages that terminate a programme and impose fines in the case of non-compliance. Further, there is broad acceptance of programmes that entail long-run redistribution towards poorer countries. Financing the assistance through a progressive tax increase is more popular than through a flat tax increase. In general, there is substantial scope for constructing assistance packages that command majority support in all sample countries, particularly if programmes have spending conditionality and progressive tax financing.
Silent brain infarcts impact on cognitive function in atrial fibrillation
Authors: Kühne Michael , Krisai Philipp , Coslovsky Michael , Rodondi Nicolas , Müller Andreas , Beer Jürg H , Ammann Peter , Auricchio Angelo , Moschovitis Giorgio , Hayoz Daniel , Kobza Richard , Shah Dipen , Stephan Frank Peter , Schläpfer Jürg , Di Valentino Marcello , Aeschbacher Stefanie , Ehret Georg , Eken Ceylan , Monsch Andreas , Roten Laurent , Schwenkglenks Matthias , Springer Anne , Sticherling Christian , Reichlin Tobias , Zuern Christine S , Meyre Pascal B , Blum Steffen , Sinnecker Tim , Würfel Jens , Bonati Leo H. , Conen David , Osswald Stefan ,   for the Swiss-AF Investigators
Published: January 2022

Abstract

Aims
We aimed to investigate the association of clinically overt and silent brain lesions with cognitive function in atrial fibrillation (AF) patients.

Methods and results
We enrolled 1227 AF patients in a prospective, multicentre cohort study (Swiss-AF). Patients underwent standardized brain magnetic resonance imaging (MRI) at baseline and after 2 years. We quantified new small non-cortical infarcts (SNCIs) and large non-cortical or cortical infarcts (LNCCIs), white matter lesions (WML), and microbleeds (Mb). Clinically, silent infarcts were defined as new SNCI/LNCCI on follow-up MRI in patients without a clinical stroke or transient ischaemic attack (TIA) during follow-up. Cognition was assessed using validated tests. The mean age was 71 years, 26.1% were females, and 89.9% were anticoagulated. Twenty-eight patients (2.3%) experienced a stroke/TIA during 2 years of follow-up. Of the 68 (5.5%) patients with ≥1 SNCI/LNCCI, 60 (88.2%) were anticoagulated at baseline and 58 (85.3%) had a silent infarct. Patients with brain infarcts had a larger decline in cognition [median (interquartile range)] changes in Cognitive Construct score [−0.12 (−0.22; −0.07)] than patients without new brain infarcts [0.07 (−0.09; 0.25)]. New WML or Mb were not associated with cognitive decline.

Conclusion
In a contemporary cohort of AF patients, 5.5% had a new brain infarct on MRI after 2 years. The majority of these infarcts was clinically silent and occurred in anticoagulated patients. Clinically, overt and silent brain infarcts had a similar impact on cognitive decline.

Clinical Trial Registration
ClinicalTrials.gov Identifier: NCT02105844, https://clinicaltrials.gov/ct2/show/NCT02105844
Predicting daily COVID-19 case rates from SARS-CoV-2 RNA concentrations across a diversity of wastewater catchments
Authors: Zulli Alessandro , Pan Annabelle , Bart Stephen M , Crawford Forrest W , Kaplan Edward H , Cartter Matthew , Ko Albert I , Sanchez Marcela , Brown Cade , Cozens Duncan , Brackney Doug E , Peccia Jordan 
Published: January 2022

AbstractWe assessed the relationship between municipality COVID-19 case rates and SARS-CoV-2 concentrations in the primary sludge of corresponding wastewater treatment facilities. Over 1700 daily primary sludge samples were collected from six wastewater treatment facilities with catchments serving 18 cities and towns in the State of Connecticut, USA. Samples were analyzed for SARS-CoV-2 RNA concentrations during a 10 month time period that overlapped with October 2020 and winter/spring 2021 COVID-19 outbreaks in each municipality. We fit lagged regression models to estimate reported case rates in the six municipalities from SARS-CoV-2 RNA concentrations collected daily from corresponding wastewater treatment facilities. Results demonstrate the ability of SARS-CoV-2 RNA concentrations in primary sludge to estimate COVID-19 reported case rates across treatment facilities and wastewater catchments, with coverage probabilities ranging from 0.94 to 0.96. Lags of 0 to 1 days resulted in the greatest predictive power for the model. Leave-one-out cross validation suggests that the model can be broadly applied to wastewater catchments that range in more than one order of magnitude in population served. The close relationship between case rates and SARS-CoV-2 concentrations demonstrates the utility of using primary sludge samples for monitoring COVID-19 outbreak dynamics. Estimating case rates from wastewater data can be useful in locations with limited testing availability, testing disparities, or delays in individual COVID-19 testing programs.
The diversity of heme sensor systems – heme-responsive transcriptional regulation mediated by transient heme protein interactions
Authors: Krüger Aileen , Keppel Marc , Sharma Vikas , Frunzke Julia 
Published: January 2022

Abstract
Heme is a versatile molecule that is vital for nearly all cellular life by serving as prosthetic group for various enzymes or as nutritional iron source for diverse microbial species. However, elevated levels of heme is toxic to cells. The complexity of this stimulus has shaped the evolution of diverse heme sensor systems, which are involved in heme-dependent transcriptional regulation in eukaryotes and prokaryotes. The functions of these systems are manifold—ranging from the specific control of heme detoxification or uptake systems to the global integration of heme and iron homeostasis. This review focuses on heme sensor systems, regulating heme homeostasis by transient heme protein interaction. We provide an overview of known heme-binding motifs in prokaryotic and eukaryotic transcription factors. Besides the central ligands, the surrounding amino acid environment was shown to play a pivotal role in heme binding. The diversity of heme-regulatory systems, therefore, illustrates that prediction based on pure sequence information is hardly possible and requires careful experimental validation. Comprehensive understanding of heme-regulated processes is not only important for our understanding of cellular physiology, but also provides a basis for the development of novel antibacterial drugs and metabolic engineering strategies.
Haplotype-based inference of the distribution of fitness effects
Authors: Ortega-Del Vecchyo Diego , Lohmueller Kirk E , Novembre John 
Published: January 2022

Abstract
Recent genome sequencing studies with large sample sizes in humans have discovered a vast quantity of low-frequency variants, providing an important source of information to analyze how selection is acting on human genetic variation. In order to estimate the strength of natural selection acting on low-frequency variants, we have developed a likelihood-based method that uses the lengths of pairwise identity-by-state between haplotypes carrying low-frequency variants. We show that in some nonequilibrium populations (such as those that have had recent population expansions) it is possible to distinguish between positive or negative selection acting on a set of variants. With our new framework, one can infer a fixed selection intensity acting on a set of variants at a particular frequency, or a distribution of selection coefficients for standing variants and new mutations. We show an application of our method to the UK10K phased haplotype dataset of individuals.
Linkage disequilibrium between rare mutations
Authors: Good Benjamin H 
Published: January 2022

Abstract
The statistical associations between mutations, collectively known as linkage disequilibrium, encode important information about the evolutionary forces acting within a population. Yet in contrast to single-site analogues like the site frequency spectrum, our theoretical understanding of linkage disequilibrium remains limited. In particular, little is currently known about how mutations with different ages and fitness costs contribute to expected patterns of linkage disequilibrium, even in simple settings where recombination and genetic drift are the major evolutionary forces. Here, I introduce a forward-time framework for predicting linkage disequilibrium between pairs of neutral and deleterious mutations as a function of their present-day frequencies. I show that the dynamics of linkage disequilibrium become much simpler in the limit that mutations are rare, where they admit a simple heuristic picture based on the trajectories of the underlying lineages. I use this approach to derive analytical expressions for a family of frequency-weighted linkage disequilibrium statistics as a function of the recombination rate, the frequency scale, and the additive and epistatic fitness costs of the mutations. I find that the frequency scale can have a dramatic impact on the shapes of the resulting linkage disequilibrium curves, reflecting the broad range of time scales over which these correlations arise. I also show that the differences between neutral and deleterious linkage disequilibrium are not purely driven by differences in their mutation frequencies and can instead display qualitative features that are reminiscent of epistasis. I conclude by discussing the implications of these results for recent linkage disequilibrium measurements in bacteria. This forward-time approach may provide a useful framework for predicting linkage disequilibrium across a range of evolutionary scenarios.
Early-Life Factors as Predictors of Age-Associated Deficit Accumulation Across 17 Years From Midlife Into Old Age
Authors: Haapanen Markus J , Jylhävä Juulia , Kortelainen Lauri , Mikkola Tuija M , Salonen Minna , Wasenius Niko S , Kajantie Eero , Eriksson Johan G , von Bonsdorff Mikaela B 
Published: January 2022

Abstract

Background
Early-life exposures have been associated with the risk of frailty in old age. We investigated whether early-life exposures predict the level and rate of change in a frailty index (FI) from midlife into old age.

Methods
A linear mixed model analysis was performed using data from 3 measurement occasions over 17 years in participants from the Helsinki Birth Cohort Study (n = 2 000) aged 57–84 years. A 41-item FI was calculated on each occasion. Information on birth size, maternal body mass index (BMI), growth in infancy and childhood, childhood socioeconomic status (SES), and early-life stress (wartime separation from both parents) was obtained from registers and health care records.

Results
At age 57 years the mean FI level was 0.186 and the FI levels increased by 0.34%/year from midlife into old age. Larger body size at birth associated with a slower increase in FI levels from midlife into old age. Per 1 kg greater birth weight the increase in FI levels per year was −0.087 percentage points slower (95% confidence interval = −0.163, −0.011; p = 0.026). Higher maternal BMI was associated with a higher offspring FI level in midlife and a slower increase in FI levels into old age. Larger size, faster growth from infancy to childhood, and low SES in childhood were all associated with a lower FI level in midlife but not with its rate of change.

Conclusions
Early-life factors seem to contribute to disparities in frailty from midlife into old age. Early-life factors may identify groups that could benefit from frailty prevention, optimally initiated early in life.
Serum levels of C-Terminal Telopeptide (CTX) are Associated with Muscle Function in Community-Dwelling Older Adults
Authors: Kirk Ben , Lieu Nicky , Vogrin Sara , Sales Myrla , Pasco Julie A , Duque Gustavo 
Published: January 2022

Abstract

Background
Markers of bone metabolism have been associated with muscle mass and function. Whether serum cross-linked C-terminal telopeptides of type I collagen (CTX) is also associated with these measures in older adults remains unknown.

Methods
In community-dwelling older adults at high risk of falls and fractures, serum CTX (biochemical immunoassays) was used as the exposure, while appendicular lean mass (dual-energy x-ray absorptiometry) and muscle function (grip strength [hydraulic dynamometer], short physical performance battery [SPPB], gait speed, sit-to-stand, balance, Timed Up and Go [TUG]) were used as outcomes. Potential covariates including demographic, lifestyle, and clinical factors were considered in statistical models. Areas under the receiver operating characteristic (ROC) curves were calculated for significant outcomes.

Results
Two hundred and ninety-nine older adults (median age: 79 years, interquartile range: 73, 84; 75.6% women) were included. In multivariable models, CTX was negatively associated with SPPB (β = 0.95, 95% confidence interval [CI]: 0.92, 0.98) and balance (β = 0.92, 0.86, 0.99) scores, and positively associated with sit-to-stand (β = 1.02, 95% CI: 1.00, 1.05) and TUG (β = 1.03, 95% CI: 1.00, 1.05). Trend line for gait speed (β = 0.99, 95% CI: 0.98, 1.01) was in the hypothesized direction but did not reach significance. Area under the ROC curves showed low diagnostic power (&lt;0.7) of CTX in identifying poor muscle function (SPPB: 0.63; sit-to-stand: 0.64; TUG: 0.61).

Conclusions
In older adults, higher CTX levels were associated with poorer lower-limb muscle function (but showed poor diagnostic power for these measures). These clinical data build on the biomedical link between bone and muscle.
Hormonal interactions underlying parthenocarpic fruit formation in horticultural crops
Authors: Sharif Rahat , Su Li , Chen Xuehao , Qi Xiaohua 
Published: January 2022

AbstractIn some horticultural crops, such as Cucurbitaceae, Solanaceae, and Rosaceae species, fruit set and development can occur without the fertilization of ovules, a process known as parthenocarpy. Parthenocarpy is an important agricultural trait that can not only mitigate fruit yield losses caused by environmental stresses but can also induce the development of seedless fruit, which is a desirable trait for consumers. In the present review, the induction of parthenocarpic fruit by the application of hormones such as auxins (2,4 dichlorophenoxyacetic acid; naphthaleneacetic acid), cytokinins (forchlorfenuron; 6-benzylaminopurine), gibberellic acids, and brassinosteroids is first presented. Then, the molecular mechanisms of parthenocarpic fruit formation, mainly related to plant hormones, are presented. Auxins, gibberellic acids, and cytokinins are categorized as primary players in initiating fruit set. Other hormones, such as ethylene, brassinosteroids, and melatonin, also participate in parthenocarpic fruit formation. Additionally, synergistic and antagonistic crosstalk between these hormones is crucial for deciding the fate of fruit set. Finally, we highlight knowledge gaps and suggest future directions of research on parthenocarpic fruit formation in horticultural crops.