bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visuomotor integration deficits are common to familial and sporadic preclinical Alzheimer’s disease
Authors: Lu Kirsty , Nicholas Jennifer M , Weston Philip S J , Stout Julie C , O’Regan Alison M , James Sarah-Naomi , Buchanan Sarah M , Lane Christopher A , Parker Thomas D , Keuss Sarah E , Keshavan Ashvini , Murray-Smith Heidi , Cash David M , Sudre Carole H , Malone Ian B , Coath William , Wong Andrew , Richards Marcus , Henley Susie M D , Fox Nick C , Schott Jonathan M , Crutch Sebastian J 
Published: January 2021

Abstract
We investigated whether subtle visuomotor deficits were detectable in familial and sporadic preclinical Alzheimer’s disease. A circle-tracing task—with direct and indirect visual feedback, and dual-task subtraction—was completed by 31 individuals at 50% risk of familial Alzheimer’s disease (19 presymptomatic mutation carriers; 12 non-carriers) and 390 cognitively normal older adults (members of the British 1946 Birth Cohort, all born during the same week; age range at assessment = 69–71 years), who also underwent β-amyloid-PET/MRI to derive amyloid status (positive/negative), whole-brain volume and white matter hyperintensity volume. We compared preclinical Alzheimer’s groups against controls cross-sectionally (mutation carriers versus non-carriers; amyloid-positive versus amyloid-negative) on speed and accuracy of circle-tracing and subtraction. Mutation carriers (mean 7 years before expected onset) and amyloid-positive older adults traced disproportionately less accurately than controls when visual feedback was indirect, and were slower at dual-task subtraction. In the older adults, the same pattern of associations was found when considering amyloid burden as a continuous variable (Standardized Uptake Value Ratio). The effect of amyloid was independent of white matter hyperintensity and brain volumes, which themselves were associated with different aspects of performance: greater white matter hyperintensity volume was also associated with disproportionately poorer tracing accuracy when visual feedback was indirect, whereas larger brain volume was associated with faster tracing and faster subtraction. Mutation carriers also showed evidence of poorer tracing accuracy when visual feedback was direct. This study provides the first evidence of visuomotor integration deficits common to familial and sporadic preclinical Alzheimer’s disease, which may precede the onset of clinical symptoms by several years.
Microbial intrusion and seasonal dynamics in the groundwater microbiome of a porous basaltic rock aquifer used as municipal water reservoir
Authors: Knobloch Stephen , Klonowski Alexandra Maria , Tómasdóttir Sigrún , Kristjánsson Bjarni Reyr , Guðmundsson Sverrir , Marteinsson Viggó Þór 
Published: January 2021

ABSTRACT
Groundwater is a key resource for safe drinking water supply. Yet unconfined aquifers can be vulnerable to microbial contamination during extreme weather events that lead to surface runoff. The current study characterises the groundwater microbiome of a porous basaltic rock aquifer in South-West Iceland used for drinking water extraction and analyses the microbial community dynamics during surface runoff. The groundwater microbial community sampled from 12 wells across the extraction area contained over 745 prokaryotic genera and was phylogenetically similar between wells and most seasons, representing a diverse but homogenous ecosystem. The largest seasonal variation in the microbial community composition was detected during a period of concurrent snow melt and high precipitation leading to surface runoff. This period was characterised by an increased abundance of soil-associated taxa in the groundwater microbiome and specifically of taxa assigned to Aeromonas and Bacillus. A field experiment simulating high surface runoff around a groundwater well confirmed the increased abundance of surface soil microorganisms in the well water, indicating vulnerability of groundwater towards surface microbial intrusion during extreme weather events. As such events are likely to increase due to climate change, novel water management tools such as microbial community analysis could help ensure drinking water safety.
Taking Constitutionalization Seriously: European IP Law, Weak Fundamental Rights and the Network of Courts
Authors: Goldhammer Michael 
Published: January 2021

Abstract
A set of three recent decisions delivered by the CJEU – Spiegel Online,1 Pelham2 and Funke Medien3 – deepens the widespread interpretation of European IP law through the lenses of constitutionalization. While there is no unitary understanding of constitutionalization, many scholars associate it with the growing influence of fundamental rights on European IP law – both within and beyond the statutory body. In fact, the case law provides plenty of evidence on how the Charter of Fundamental Rights and proportionality – its central method – is deployed to steer the implementation of EU law by domestic courts. However, as the said decisions also show, there are still a lot of questions and frustration. While we have to acknowledge that the CJEU takes fundamental rights into account when interpreting IP law, some critics see deficits when the Court strictly rejects the idea of external limitations on exclusive copyrights. European fundamental rights are – obviously – not a trump card. This article aims to clarify some misleading aspirations by re-examining both the idea of constitutionalization and its impact on European IP law. It will argue that weak or evasive fundamental rights are not necessarily a sign of deficient constitutionalization, they might rather be the consequence thereof.
Current Topics in Marmoset Anesthesia and Analgesia
Authors: Goodroe Anna , Fitz Casey , Bakker Jaco 
Published: January 2021

Abstract
Anesthetic and analgesics are essential components of both clinical and research procedures completed in marmosets. A review of current anesthetic and analgesic regimens for marmosets has been complied to provide a concise reference for veterinarians and investigator teams. Published dose regimens for injectable and inhalant anesthetic drugs and analgesic drugs are included. Appropriate physiological monitoring is key to the success of the procedure and perianesthetic options are provided. Although recent publications have refined anesthesia and analgesia practices, our review demonstrates the continued need for evidence-based resources specific to marmosets.
Models for plasma kinetics during simultaneous therapeutic plasma exchange and extracorporeal membrane oxygenation
Authors: Puelz Charles , Danial Zach , Raval Jay S , Marinaro Jonathan L , Griffith Boyce E , Peskin Charles S 
Published: January 2021

Abstract
This paper focuses on the derivation and simulation of mathematical models describing new plasma fraction in blood for patients undergoing simultaneous extracorporeal membrane oxygenation and therapeutic plasma exchange. Models for plasma exchange with either veno-arterial or veno-venous extracorporeal membrane oxygenation are considered. Two classes of models are derived for each case, one in the form of an algebraic delay equation and another in the form of a system of delay differential equations. In special cases, our models reduce to single compartment ones for plasma exchange that have been validated with experimental data (Randerson et al., 1982, Artif. Organs, 6, 43–49). We also show that the algebraic differential equations are forward Euler discretizations of the delay differential equations, with timesteps equal to transit times through model compartments. Numerical simulations are performed to compare different model types, to investigate the impact of plasma device port switching on the efficiency of the exchange process, and to study the sensitivity of the models to their parameters.
Distribution and Temporal Dynamics of Plasmodium falciparum Chloroquine Resistance Transporter Mutations Associated With Piperaquine Resistance in Northern Cambodia
Authors: Shrestha Biraj , Shah Zalak , Morgan Andrew P , Saingam Piyaporn , Chaisatit Chaiyaporn , Chaorattanakawee Suwanna , Praditpol Chantida , Boonyalai Nonlawat , Lertsethtakarn Paphavee , Wojnarski Mariusz , Deutsch-Feldman Molly , Adams Matthew , Sea Darapiseth , Chann Soklyda , Tyner Stuart D , Lanteri Charlotte A , Spring Michele D , Saunders David L , Smith Philip L , Lon Chanthap , Gosi Panita , Sok Somethy , Satharath Prom , Rekol Huy , Lek Dysoley , Vesely Brian A , Lin Jessica T , Waters Norman C , Takala-Harrison Shannon 
Published: January 2021

Abstract

Background
Newly emerged mutations within the Plasmodium falciparum chloroquine resistance transporter (PfCRT) can confer piperaquine resistance in the absence of amplified plasmepsin II (pfpm2). In this study, we estimated the prevalence of co-circulating piperaquine resistance mutations in P. falciparum isolates collected in northern Cambodia from 2009 to 2017.

Methods
The sequence of pfcrt was determined for 410 P. falciparum isolates using PacBio amplicon sequencing or whole genome sequencing. Quantitative polymerase chain reaction was used to estimate pfpm2 and pfmdr1 copy number.

Results
Newly emerged PfCRT mutations increased in prevalence after the change to dihydroartemisinin-piperaquine in 2010, with &gt;98% of parasites harboring these mutations by 2017. After 2014, the prevalence of PfCRT F145I declined, being outcompeted by parasites with less resistant, but more fit PfCRT alleles. After the change to artesunate-mefloquine, the prevalence of parasites with amplified pfpm2 decreased, with nearly half of piperaquine-resistant PfCRT mutants having single-copy pfpm2.

Conclusions
The large proportion of PfCRT mutants that lack pfpm2 amplification emphasizes the importance of including PfCRT mutations as part of molecular surveillance for piperaquine resistance in this region. Likewise, it is critical to monitor for amplified pfmdr1 in these PfCRT mutants, as increased mefloquine pressure could lead to mutants resistant to both drugs.
Matrix degradation and cell proliferation are coupled to promote invasion and escape from an engineered human breast microtumor
Authors: Rabie Emann M , Zhang Sherry X , Kourouklis Andreas P , Kilinc A Nihan , Simi Allison K , Radisky Derek C , Tien Joe , Nelson Celeste M 
Published: January 2021

Abstract
Metastasis, the leading cause of mortality in cancer patients, depends upon the ability of cancer cells to invade into the extracellular matrix that surrounds the primary tumor and to escape into the vasculature. To investigate the features of the microenvironment that regulate invasion and escape, we generated solid microtumors of MDA-MB-231 human breast carcinoma cells within gels of type I collagen. The microtumors were formed at defined distances adjacent to an empty cavity, which served as an artificial vessel into which the constituent tumor cells could escape. To define the relative contributions of matrix degradation and cell proliferation on invasion and escape, we used pharmacological approaches to block the activity of matrix metalloproteinases (MMPs) or to arrest the cell cycle. We found that blocking MMP activity prevents both invasion and escape of the breast cancer cells. Surprisingly, blocking proliferation increases the rate of invasion but has no effect on that of escape. We found that arresting the cell cycle increases the expression of MMPs, consistent with the increased rate of invasion. To gain additional insight into the role of cell proliferation in the invasion process, we generated microtumors from cells that express the fluorescent ubiquitination-based cell cycle indicator. We found that the cells that initiate invasions are preferentially quiescent, whereas cell proliferation is associated with the extension of invasions. These data suggest that matrix degradation and cell proliferation are coupled during the invasion and escape of human breast cancer cells and highlight the critical role of matrix proteolysis in governing tumor phenotype.
Biosynthesis of sulfonamide and sulfamate antibiotics in actinomycete
Authors: Awakawa Takayoshi , Barra Lena , Abe Ikuro 
Published: January 2021

Abstract
Sulfonamides and sulfamates are a group of organosulfur compounds that contain the signature sulfamoyl structural motif. These compounds were initially only known as synthetic antibacterial drugs but were later also discovered as natural products. Eight highly potent examples have been isolated from actinomycetes to date, illustrating the large biosynthetic repertoire of this bacterial genus. For the biosynthesis of these compounds, several distinct and unique biosynthetic machineries have been discovered, capable to generate the unique S–N bond. For the creation of novel, second generation natural products by biosynthetic engineering efforts, a detailed understanding of the underlying enzyme machinery toward potent structural motifs is crucial. In this review, we aim to summarize the current state of knowledge on sulfonamide and sulfamate biosynthesis. A detailed discussion for the secondary sulfamate ascamycin, the tertiary sulfonamide sulfadixiamycin A, and the secondary sulfonamide SB-203208 is provided and their bioactivities and mode of actions are discussed.
‘That would be dreadful’: The ethical, legal, and social challenges of sharing your Alzheimer’s disease biomarker and genetic testing results with others
Authors: Largent Emily A , Stites Shana D , Harkins Kristin , Karlawish Jason 
Published: January 2021

Abstract
Several large clinical trials are underway to discover therapies to delay or prevent the onset of dementia caused by Alzheimer’s disease (AD). A common feature of these trials is that they are testing therapies in people who do not yet have changes in memory or thinking—that is, who are cognitively unimpaired—but who have a biologically defined risk of developing dementia caused by AD. When these trials eventually succeed, it is reasonable to expect the widespread adoption of biomarker and genetic testing of cognitively unimpaired individuals into clinical practice, as well as treatment prescribed to individuals at heightened risk. Here, we report results from two qualitative studies that sought to understand with whom, why, and how individuals share their AD biomarker and genetic testing results, respectively. We found that sharing is common within the confines of close relationships. However, when sharing outside such relationships, people have multiple concerns, including stigma and discrimination. These concerns highlight the need for additional legal protections and policy changes in anticipation of the coming transformation of AD clinical care.
Recurrent intestinal obstruction due to gallstone ileus during same hospital admission: a case report and literature review
Authors: Alnahari Danah I , Almalki Sami A , Alabeidi Fahad A 
Published: January 2021

Abstract
Gallstone ileus (GSI) is an uncommon entity that causes obstruction of the intestinal lumen due to gallstones. It affects mainly the elderly with multiple comorbidities, leading to a high mortality rate. In this case, an 81-year-old woman was admitted due to GSI. She had a recurrence after 5 days of the index surgery. Recurrent intestinal obstruction due to GSI during the same hospitalization despite complete clearance of the small bowel from stones is rare. Through our case, we will discuss management along with a review of the current evidence.
The F-box protein MIO1/SLB1 regulates organ size and leaf movement in Medicago truncatula
Authors: Zhou Shaoli , Yang Tianquan , Mao Yawen , Liu Ye , Guo Shiqi , Wang Ruoruo , Fangyue Genwang , He Liangliang , Zhao Baolin , Bai Quanzi , Li Youhan , Zhang Xiaojia , Wang Dongfa , Wang Chaoqun , Wu Qing , Yang Yuanfan , Liu Yu , Tadege Million , Chen Jianghua 
Published: January 2021

Abstract
The size of leaf and seed organs, determined by the interplay of cell proliferation and expansion, is closely related to the final yield and quality of forage and crops. Yet the cellular and molecular mechanisms underlying organ size modulation remain poorly understood, especially in legumes. Here, MINI ORGAN1 (MIO1), which encodes an F-box protein SMALL LEAF AND BUSHY1 (SLB1) recently reported to control lateral branching in Medicago truncatula, was identified as a key regulator of organ size. We show that loss-of-function of MIO1/SLB1 severely reduced organ size. Conversely, plants overexpressing MIO1/SLB1 had enlarged organs. Cellular analysis revealed that MIO1/SLB1 controlled organ size mainly by modulating primary cell proliferation during the early stages of leaf development. Biochemical analysis revealed that MIO1/SLB1 could form part of SKP1/Cullin/F-box (SCF) E3 ubiquitin ligase complex, to target BIG SEEDS1 (BS1), a repressor of primary cell division, for degradation. Interestingly, we found that MIO1/SLB1 also played a key role in pulvinus development and leaf movement by modulating cell proliferation of the pulvinus as leaves developed. Our study not only demonstrates a conserved role of MIO1/SLB1 in the control of organ size in legumes, but also sheds light on the novel function of MIO1/SLB1 in leaf movement.
Epidemiology and Outcomes of Vancomycin-Resistant Enterococcus Infections in the U.S. Military Health System
Authors: Stagliano David R , Susi Apryl , Adams Daniel J , Nylund Cade M 
Published: January 2021

ABSTRACT

Introduction
Vancomycin-resistant enterococci (VRE) are classified by the Centers for Diseases Control and Prevention as a serious antibiotic resistance threat. Our study aims to characterize the epidemiology, associated conditions, and outcomes of VRE infections among hospitalized patients in the U.S. military health system (MHS).

Materials and Methods
We performed a retrospective cohort study of patients with VRE infection using the MHS database. Cases included all patients admitted to a military treatment facility for ≥2 days from October 2008 to September 2015 with a clinical culture growing Enterococcus faecalis, Enterococcus faecium, or Enterococcus species (unspecified), reported as resistant to vancomycin. Co-morbid conditions and procedures associated with VRE infection were identified by multivariable conditional logistic regression. Patient case-mix adjusted outcomes including in-hospital mortality, length of stay, and hospitalization cost were evaluated by high-dimensional propensity score adjustment.

Results
During the seven-year study period and among 1,161,335 hospitalized patients within the MHS, we identified 577 (0.05%) patients with VRE infection. A majority of VRE infections were urinary tract infections (57.7%), followed by bloodstream (24.7%), other site/device-related (12.9%), respiratory (2.9%), and wound infections (1.8%). Risk factors for VRE infection included invasive gastrointestinal, pulmonary, and urologic procedures, indwelling devices, and exposure to 4th generation cephalosporins, but not to glycopeptides. Patients hospitalized with VRE infection had significantly higher hospitalization costs (attributable difference [AD] $135,534, P&lt;0.001), prolonged hospital stays (AD 20.44 days, P&lt;0.001, and higher in-hospital mortality (case-mix adjusted odds ratio 5.77; 95% confidence interval 4.59-7.25).

Conclusions
VRE infections carry a considerable burden for hospitalized patients given their impact on length of stay, hospitalization costs, and in-hospital mortality. Active surveillance and infection control efforts should target those identified as high-risk for VRE infection. Antimicrobial stewardship programs should focus on limiting exposure to 4th generation cephalosporins.
Enhancing Language Access: A Pilot Study to Examine the Importance of Understanding the Language Preference and Acculturalization Level in the Provision of Healthcare for Hispanics Veterans With Traumatic Brain Injury
Authors: Molina-Vicenty Irma L , Borrás-Fernandez Isabel C , Pope Charlene , Davis Boyd , Alemán-Del Toro Martha , Maldonado-Sánchez Irma , Arroyo Lillian , Jovet-Toledo Gerardo , Dismuke Clara E , Roque Alexandra , Díaz Yahaira , Resto Milagros , Rincones Alexandra , Soler-Llompart Cecilia , Acevedo Neishaliz-Díaz , Betances-Arroyo Gabriela S 
Published: January 2021

ABSTRACT

Introduction
The purpose of this pilot study was to obtain preliminary data to culturally adapt the Veteran Health Administration Traumatic Brain Injury (TBI) assessment instruments for the Hispanic Veteran population. A qualitative analysis explored the cognitive processes used by Hispanic Veterans whose preferred language was Spanish to understand a specific set of screening questions within the Initial TBI Screening, the Comprehensive TBI Evaluation, the Neurobehavioral Symptom Inventory (NSI), and the La Trobe Communication Questionnaire (LTCQ).

Materials and Methods
A certified translator completed translation of the TBI instruments, an expert panel resolved inadequate expressions of the translations, and translated instruments were back translated. Male and female Hispanic Veterans with a positive TBI screening underwent a recorded administration of the TBI instruments, including LTCQ, followed by systematic debriefing using semi-structured cognitive interviews which then underwent qualitative analysis. The Marin’s Short Acculturation Scale for Hispanics, the Tropp’s Psychological Acculturation Scale, the English-Language Proficiency Test Series, and the TBI Demographic and Language Preference interview were administered to the subjects.

Results
Fifteen subjects were enrolled for the TBI instruments intervention; 11 of them completed all the additional procedures. The TBI instruments intervention seemed to produce very few variations, indicating adequate cultural equivalence. However, the LTCQ instrument showed suggested cultural variations, but did not suggest a lack of understanding or misinterpretation. The population studied displayed preferential connectedness to the Hispanic/Latino culture and to the Spanish language. The LTCQ indicated that subjects perceived themselves as having a worse execution in terms of communication skills than historical control and TBI groups. English-Language Proficiency Test Series found that most of the subject population did not demonstrate mastery of grade-appropriate basic social and academic vocabulary in English.

Conclusion
Current findings highlight the importance of using linguistically and culturally appropriate materials upon evaluating Hispanic Veterans with a suspected TBI who have Spanish as their primary or preferred language.
The Point Digit II: Mechanical Design and Testing of a Ratcheting Prosthetic Finger
Authors: Segil Jacob L , Pulver Ben , Huddle Stephen , Weir Richard F ff , Sliker Levin 
Published: January 2021

ABSTRACT

Introduction
People with partial hand loss represent the largest population of upper limb amputees by a factor of 10. The available prosthetic componentry for people with digit loss provide various methods of control, kinematic designs, and functional abilities. Here, the Point Digit II is empirically tested and a discussion is provided comparing the Point Digit II with the existing commercially available prosthetic fingers.

Materials and Methods
Benchtop mechanical tests were performed using prototype Point Digit II prosthetic fingers. The battery of tests included a static load test, a static mounting tear-out test, a dynamic load test, and a dynamic cycle test. These tests were implemented to study the mechanisms within the digit and the ability of the device to withstand heavy-duty use once out in the field.

Results
The Point Digit II met or exceeded all geometric and mechanical specifications. The device can withstand over 300 lbs of force applied to the distal phalange and was cycled over 250,000 times without an adverse event representing 3 years of use. Multiple prototypes were utilized across all tests to confirm the ability to reproduce the device in a reliable manner.

Conclusions
The Point Digit II presents novel and exciting features to help those with partial hand amputation return to work and regain ability. The use of additive manufacturing, unique mechanism design, and clinically relevant design features provides both the patient and clinician with a prosthetic digit, which improves upon the existing devices available.