bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hundred Years of Insulin Therapy: Purified Early Insulins
Authors: Lapolla Annunziata , Dalfrà Maria G. 
Published: November 2019

Background:
The discovery of insulin has changed dramatically the outcome of patients with type 1 diabetes, giving them the possibility to survive. This is of particular concern due to the fact that type 1 diabetes most frequently occurs in children who were destined to die in ketoacidosis coma.

Areas of Uncertainty:
From insulin discovery to the availability of human insulin and human insulin analogs to be used in diabetes therapy, a series of problems have arisen as the difficulty of insulin purifications, the animal insulin used by the first researches were in fact contaminated by proteins, fats, and other impurities, and the presence of side effects such as allergy, antibodies generation, and lipoatrophy.

Data Source Literature:
Data strictly related to the argument have been searched in Pub Med and used.

Results:
Starting from insulin discovery in 1921 to nowadays, significant efforts have been made by a series of researches to purify animal insulin, discover the molecular structure of human insulin, and develop methods to synthetize human insulin and then insulin analogs.

Conclusions:
The history of insulin discovery here reported is fascinating; insulin is a hormone, a product of biotechnology, a field of research that saved and save the life of many diabetic patients.
Adherence, Medical Outcomes, and Health Care Costs in Adolescents/Young Adults Following Pediatric Liver Transplantation
Authors: Lawrence Zoe E. , Martinez Mercedes , Lobritto Steven , Chen Justin , Breslin Nadine , Fox Alyson , Vittorio Jennifer 
Published: November 2019

ABSTRACTObjective:Improved outcomes after pediatric liver transplantation (LT) have led to increasing numbers of adolescent and young adult recipients entering into adult health care systems. The aim of this study was to evaluate the impact of transition from pediatric to adult health care models on medical outcomes, measures of adherence, and health care utilization for pediatric LT recipients.Methods:We evaluated the course of patients who received an LT while followed in pediatrics and transferred to an adult care provider within our institution. Data were collected from 2 years preceding and 2 years following transfer of care.Results:A total of 32 patients were eligible for analysis. Median age at time of transfer was 22.9 years (interquartile range 21.7–23.6). Nine patients (28%) died following transfer of care. There was a significant decrease in office visit adherence following transfer of care (P = 0.02). Although not achieving significance, an increase in alanine aminotransferase values, episodes of acute cellular rejection, progression to cirrhosis, evolution to chronic rejection, and hospital admission rates post transfer were found. These findings were associated with an increase in health care costs related to required interventions.Conclusions:Our study demonstrates trends toward worse health outcomes, decreased adherence, and increased health care utilization following transfer of care. These findings and poor patient survival suggest that the time around transition from pediatric to adult health care models represents a period of increased vulnerability for pediatric LT recipients. Larger, multicenter, prospective studies are needed to identify factors and interventions that affect adolescent and young adult to improve the transition process.
The Complex Relationship Among Formal Thought Disorders, Neurocognition, and Functioning in Nonacutely Ill Schizophrenia Patients
Authors: Comparelli Anna , Corigliano Valentina , Forcina Francesca , Bargagna Paride , Montalbani Benedetta , Falcone Giulia , Nardella Adele , Stampatore Lorenzo , Salzer Mark , Pompili Maurizio 
Published: November 2019

Abstract
The aims of the present study were to 1) evaluate clinical differences between patients suffering from schizophrenia (SZ) with mild versus moderate/severe formal thought disorder (FTD); 2) explore relationships between dimensions of FTD, neuropsychological domains, and global functioning; and 3) compare clinical dimensions of FTD in early and late SZ. One hundred thirty-six individuals with schizophrenia were recruited and evaluated during a nonacute phase of illness. FTD was assessed with the Thought, Language, and Communication Scale. Partial correlations, t-tests, and stepwise regression were undertaken to address the study aims. Patients with moderate/severe FTD performed worse than those with mild FTD for processing speed, reasoning and problem solving, and social cognition, and demonstrated poorer global functioning. Early SZ did not differ from late SZ in terms of negative FTD and difficulty in abstract thinking (DAT). Negative FTD was correlated with reasoning and problem solving; DAT was correlated with social cognition. All clinical dimensions of FTD, regardless of neurocognitive impairment, accounted for a significant amount of variance in global functioning. FTD predicted global functioning, regardless of neurocognitive factors. Due to their stability in different phases of the course of the disease and their strong relationship with other core variables, Neg-FTD and DAT should be investigated as an intermediate phenotype of the illness.
Effects of Physical Activity on Neurophysiological and Gene Expression Profiles in Chronic Back Pain
Authors: Kim Kyounghae , Ramesh Divya , Perry Mallory , Bernier Katherine M. , Young Erin E. , Walsh Stephen , Starkweather Angela 
Published: November 2019

Background
Despite the emphasis on exercise to reduce pain and improve function among people with chronic low back pain (cLBP), little is known about the underlying mechanism of the impact of exercise on the neurophysiological and gene transcription alterations that characterize cLBP.

Objectives
To present a study protocol to examine the feasibility, acceptability, and initial efficacy of Problem-Solving Pain to Enhance Living Well (PROPEL) with the support of nurse consultations and wearable activity-tracking technology on self-management (SM) knowledge, skills, physical activity, and pain and to examine the differential neurophysiological and gene expression profiles in cLBP participants from pre- to post-PROPEL.

Methods
A pretest and posttest study is employed on 40 adults ages 18–60 years with cLBP who do not have serious complications and/or comorbidities that affect sensorimotor function. Participants will receive video modules focused on SM and biweekly phone consultations to facilitate symptom monitoring and problem-solving while increasing physical activity frequency and duration. Participants will be assessed for outcomes including SM skills, physical activity, and pain every 2 weeks for 12 weeks. We will examine the participants’ differential neurophysiological and gene expression profiles at 12 weeks postintervention and correlate these outcomes with the total duration of physical activity.

Results
The study began in September 2018. Of the 99 subjects that were screened, 23 were enrolled and 8 completed data collection.

Discussion
Comparing the neurophysiological and gene expression profiles of people with cLBP exposed to PROPEL could inform the development of interventions that offer personalized physical activity dosage along with general SM support. Web-based programs such as PROPEL have the potential to enhance accessibility of evidence-based interventions that improve functionality and quality of life among people living with cLBP.
Agreement and Repeatability of Noncycloplegic and Cycloplegic Wavefront-based Autorefraction in Children
Authors: Rauscher Franziska G. , Lange Heike , Yahiaoui-Doktor Maryam , Tegetmeyer Helmut , Sterker Ina , Hinz Andreas , Wahl Siegfried , Wiedemann Peter , Ohlendorf Arne , Blendowske Ralf 
Published: November 2019

SIGNIFICANCE
Increasing prevalence of refractive error requires assessment of ametropia as a screening tool in children. If cycloplegia is not an option, knowledge about the increase in uncertainty for wavefront-based autorefraction is needed. The cycloplegic agent as the principal variant presents cross-reference and allows for extraction of the influence of accommodation.

PURPOSE
The purpose of this study was to determine the repeatability, agreement, and propensity to accommodate of cycloplegic (ARc) and noncycloplegic (ARnc) wavefront-based autorefraction (ZEISS i.Profiler plus; Carl Zeiss Vision, Aalen, Germany) in children aged 2 to 15 years.

METHODS
In a clinical setting, three consecutive measurements were feasible for 145 eyes (OD) under both conditions. Data are described by spherical equivalent (M), horizontal or vertical astigmatic component (J0), and oblique astigmatic component (J45). In the case of M, the most positive value of the three measurements was chosen, whereas the mean was applied for astigmatic components.

RESULTS
Regarding agreement, differences for ARc minus ARnc were statistically significant: for M, 0.55 (0.55 D; mean [SD]; P < .001), that is, more hyperopic in cycloplegia; for J0, −0.03 (0.11 D; P = .002); and for J45, −0.03 D (SD, 0.09 D; P < .001). Regarding repeatability, astigmatic components showed excellent repeatability: SD < 0.11 D (ARnc) and SD < 0.09 D (ARc). The repeatability of M was SD = 0.57 D with a 95% interval of 1.49 D (ARnc). Under cycloplegia, this decreased to SD = 0.17 D (ARc) with a 95% interval of 0.50 D. The mean propensity to accommodate was 0.44 D from repeated measurements; in cycloplegia, this was reduced to 0.19 D.

CONCLUSIONS
Wavefront-based refraction measurement results are highly repeatable and precise for astigmatic components. Noncycloplegic measurements of M show a systematic bias of 0.55 D. Cycloplegia reduces the propensity to accommodate by a factor of 2.4; for noncycloplegic repeated measurements, accommodation is controlled to a total interval of 1.49 D (95%). Without cycloplegia, results improve drastically when measurements are repeated.
Practices, Perceptions, and Attitudes in the Evaluation of Critically Ill Children for Bacteremia: A National Survey*
Authors: Woods-Hill Charlotte Z. , Koontz Danielle W. , King Anne F. , Voskertchian Annie , Colantuoni Elizabeth A. , Miller Marlene R. , Fackler James C. , Bonafide Christopher P. , Milstone Aaron M. , Xie Anping 
Published: November 2019

Objectives:
Sending blood cultures in children at low risk of bacteremia can contribute to a cascade of unnecessary antibiotic exposure, adverse effects, and increased costs. We aimed to describe practice variation, clinician beliefs, and attitudes about blood culture testing in critically ill children.

Design:
Cross-sectional electronic survey.

Setting:
Fifteen PICUs enrolled in the Blood Culture Improvement Guidelines and Diagnostic Stewardship for Antibiotic Reduction in Critically Ill Children collaborative, an investigation of blood culture use in critically ill children in the United States.

Subjects:
PICU clinicians (bedside nurses, resident physicians, fellow physicians, nurse practitioners, physician assistants, and attending physicians).

Interventions:
None.

Measurement and Main Results:
Survey items explored typical blood culture practices, attitudes and beliefs about cultures, and potential barriers to changing culture use in a PICU setting. Fifteen of 15 sites participated, with 347 total responses, 15–45 responses per site, and an overall median response rate of 57%. We summarized median proportions and interquartile ranges of respondents who reported certain practices or beliefs: 86% (73–91%) report that cultures are ordered reflexively; 71% (61–77%) do not examine patients before ordering cultures; 90% (86–94%) obtain cultures for any new fever in PICU patients; 33% (19–61%) do not obtain peripheral cultures when an indwelling catheter is in place; and 64% (36–81%) sample multiple (vs single) lumens of central venous catheters for new fever. When asked about barriers to reducing unnecessary cultures, 80% (73–90%) noted fear of missing sepsis. Certain practices (culture source and indication) varied by clinician type. Obtaining surveillance cultures and routinely culturing all possible sources (each lumen of indwelling catheters and peripheral specimens) are positively correlated with baseline blood culture rates.

Conclusions:
There is variation in blood culture practices in the PICU. Fear and reflexive habits are common drivers of cultures. These practices may contribute to over-testing for bacteremia. Further investigation of how to optimize blood culture use is warranted.
Conservative Treatment of Tendon Injuries
Authors: Yang Shu-Mei , Chen Wen-Shiang 
Published: November 2019

Abstract
Tendon injuries or tendinopathy is a common painful and disabling conditions resulting from overuse and aging. Tendinopathy remains a challenging clinical problem because response to different treatment modalities is usually unsatisfactory and recovery is slow. We performed an extensive literature review focusing on nonsurgical treatment options for tendinopathies, including nonsteroidal anti-inflammatory drugs, corticosteroid, eccentric exercise, extracorporeal shock wave therapy, therapeutic ultrasound, hyaluronic acid, platelet-rich plasma, prolotherapy, polydeoxyribonucleotide, and stem cells, aimed at providing the most updated evidence as a guideline for caregivers.
Reliability, Validity, and Sensitivity to Change of the Cochin Hand Functional Disability Scale and Testing the New 6-Item Cochin Hand Functional Disability Scale in Systemic Sclerosis
Authors: Gheorghiu Ana Maria , Gyorfi Hermina , Capotă Răzvan , Matei Alexandru , Oneaţă Raida , Bojincă Mihai , Stoica Victor , Mihai Carina 
Published: November 2019

Systemic sclerosis (SSc) is a chronic autoimmune disease causing complex hand disability. A reliable tool for hand function assessment in SSc is the Cochin Hand Functional Disability Scale (CHFS). More recently, a short-form CHFS of 6 items (CHFS-6) has been developed.

Objectives
To validate the CHFS and the new CHFS-6 in Romanian patients with SSc.

Patients and Methods
Consecutive patients with SSc who completed the CHFS were included. All patients were assessed according to the recommendations of the European Scleroderma and Research Trials and also completed the Scleroderma Health Assessment Questionnaire and the Hand Mobility in Scleroderma questionnaire. Finger range-of-motion distances were measured.

Results
Seventy patients, 63 female and 7 male patients (age median, 53.0 years; interquartile range [IQR], 21.0 years), were included. Twenty seven had diffuse cutaneous involvement (dcSSc). Median CHFS and CHFS-6 at baseline were 25.0 (IQR, 37.0) and 8.0 (IQR, 13.0), respectively.
The internal consistency (Cronbach α = 0.96, respectively, 0.90, in all 70 patients) and test-retest reliability (intraclass correlation coefficient = 0.98 for both, in 38 patients) of both CHFS and CHFS-6 were excellent. The CHFS-6 had a very high correlation with the CHFS. There were moderate to good correlations with Hand Mobility in Scleroderma, Scleroderma Health Assessment Questionnaire, and the anthropometric measurements (construct validity). In patients with early dcSSc with a second evaluation, we found good to moderate sensitivity to change (standardized response mean of 0.8 and effect size of 0.4 for CHFS, and standardized response mean of 1.1 and effect size of 0.6 for CHFS-6).

Conclusions
The CHFS and CHFS-6 are valid and easy-to-use tools for hand involvement in SSc, which can be used in clinical or research setting.
Altered motoneuron properties contribute to motor deficits in a rabbit hypoxia ischemia model of cerebral palsy
Authors: Steele P. , Cavarsan C. F. , Dowaliby L. , Westefeld M. , Drobyshevsky A. , Gorassini M. A. , Quinlan K. A. 
Published: November 2019

AbstractCerebral palsy (CP) is caused by a variety of factors attributed to early brain damage, resulting in permanently impaired motor control, marked by weakness and muscle stiffness. To find out if altered physiology of spinal motoneurons (MNs) could contribute to movement deficits, we performed whole cell patch clamp in neonatal rabbit spinal cord slices after developmental injury at 79% gestation. After preterm hypoxia-ischemia (HI), rabbits are born with motor deficits consistent with a spastic phenotype including hypertonia and hyperreflexia. There is a range in severity, thus kits are classified as severely affected, mildly affected, or unaffected based on modified Ashworth scores and other behavioral tests. At postnatal day (P)0-5, we recorded electrophysiological parameters of 40 MNs in transverse spinal cord slices using whole cell patch clamp. Using a multivariate analysis of neuronal parameters, we found significant differences between groups (severe, mild, unaffected and sham control MNs), age (P0 to P5) and spinal cord region (cervical to sacral). Severe HI MNs showed more sustained firing patterns, depolarized resting membrane potential, and a higher threshold for action potentials. These properties could contribute to both muscle stiffness and weakness, respectively, hallmarks of spastic CP. Interestingly altered persistent inward currents (PICs) and morphology in severe HI MNs would dampen excitability (reduced normalized PIC amplitude and increased dendritic length). In summary, changes we observed in spinal MN physiology likely contribute to severity of the phenotype including weakness and hypertonia, and therapeutic strategies for CP could target excitability of spinal MNs.Key PointsPhysiology of neonatal spinal motoneurons is altered after in utero hypoxia-ischemic injuryIn motoneurons from severely affected animals there is more sustained firing (lower ΔI values), a depolarized resting potential, but a higher voltage threshold for action potential firing.Altered motoneuron excitability could contribute directly to muscle stiffness and spasticity in cerebral palsy.
Primary human macrophages are polarized towards pro-inflammatory phenotypes in alginate hydrogels
Authors: Delcassian Derfogail , Malecka Anna A. , Opoku Donaldson , Palomares Cabeza Virginia , Merry Catherine , Jackson Andrew M. 
Published: November 2019

AbstractDysregulated macrophage function is implicated in a wide range of disorders. In vitro hydrogel culture systems are often used as matrices to model and explore the effect of various external stimuli on macrophage polarization and behaviour. Here, we show that 3D alginate hydrogels are not “macrophage inert” and instead help to direct the maturation of primary human macrophages towards specific phenotypes. We compared polarization of M1-like and M2-like cells activated on planar substrates or in 3D alginate hydrogels (with or without adhesion motifs (RGD)). We show that culture in 3D alginate systems selectively alters M2 polarisation following activation; cells show a 2.6-fold increase in CD86 expression compared to cells matured on planar controls, and increase IL1β cytokine secretion even in response to an M2-like stimulus (LPS alone in the absence of IFNγ). Our results suggest that alginate materials may intrinsically stimulate M2 macrophages to acquire a unique polarization state (resembling M2b), characterized by enhanced expression of CD86 and IL1β secretion while retaining low IL12 and high IL10 secretion typical for M2 macrophages. This has important implications for researchers using alginate hydrogels to study macrophage behavior in culture and co-culture systems, as alginate itself may induce direct phenotypic changes independently or in conjunction with other stimuli.
Seed plant families with diverse mycorrhizal states have higher diversification rates
Authors: Mujica María Isabel , Burin Gustavo , Pérez María Fernanda , Quental Tiago 
Published: November 2019

AbstractA crucial innovation in plant evolution was the association with soil fungi during land colonization. Today, this symbiotic interaction is present in most plants species and can be classified in four types: arbuscular (AM), Ecto (EM), Orchid (OM) and Ericoid Mycorrhiza (ER). Since the AM ancestral state, some plants lineages have switched partner (EM, OM and ER) or lost the association (no-association: NM). Evolutionary transitions to a novel mycorrhizal state (MS) might allow plant lineages to access new resources, enhancing diversification rates. However, some clades are not restricted to one MS, and this variability might promote diversification. In this study we address the relationship between MS and diversification rates of seed plant families. For this, we used the recently published FungalRoot database, which compiled data for 14,870 species and their mycorrhizal partners. We assigned a MS to each plant family, calculated the MS heterogeneity and estimated their diversification rates using the method-of-moments. Families with mixed MS had the highest diversification rates and there was a positive relationship between MS heterogeneity and diversification rates. These results support the hypothesis that MS lability promotes diversification and highlight the importance of the association with soil fungi for the diversification of plants.
Real-time sampling of travelers shows intestinal colonization by multidrug-resistant bacteria to be a dynamic process with multiple transient acquisitions
Authors: Kantele Anu , Kuenzli Esther , Dunn Steven J , Dance David AB , Newton Paul N , Davong V , Mero Sointu , Pakkanen Sari H , Neumayr Andreas , Hatz Christoph , Snaith Ann , Kallonen Teemu , Corander Jukka , McNally Alan 
Published: November 2019

AbstractBackgroundAntimicrobial resistance (AMR) is highly prevalent in low- and middle-income countries (LMIC). International travel contributes substantially to the global spread of intestinal multidrug-resistant gram-negative (MDR-GN) bacteria. Of the 100 million annual visitors to LMIC, 30–70% become colonized by MDR-GN bacteria. The phenomenon has been well documented, but since sampling has only been conducted after travelers’ return home, data on the actual colonization process are scarce. We aimed to characterize colonization dynamics by exploring stool samples abroad on a daily basis while visiting LMIC.MethodsA group of 20 European volunteers visiting Lao People’s Democratic Republic for three weeks provided daily stool samples and filled in daily questionnaires. Acquisition of extended-spectrum beta-lactamase-producing gram-negative bacteria (ESBL-GN) was examined by selective stool cultures followed by whole-genome sequencing (WGS) of isolates.ResultsWhile colonization rates were 70% at the end of the study, daily sampling revealed that all participants had acquired ESBL-GN at some time point during their overseas stay, the colonization status varying day by day. WGS analysis ascribed the transient pattern of colonization to sequential acquisition of new strains, resulting in a loss of detectable colonization by the initial MDR-GN strains. All but one participant acquired multiple strains (n=2–7). Of the total of 83 unique strains identified (53 E. coli, 10 Klebsiella, 20 other ESBL-GN species), some were shared by as many as four subjects.ConclusionsThis is the first study to characterize in real time the dynamics of acquiring MDR-GN during travel. Our data show multiple transient colonization events indicative of constant microbial competition.
Genomic encryption of digital data stored in synthetic DNA
Authors: Grass Robert N. , Heckel Reinhard , Dessimoz Christophe , Stark Wendelin J. 
Published: November 2019

ABSTRACTToday, we can read human genomes and store digital data robustly in synthetic DNA. Here we report a strategy to intertwine these two technologies to enable the secure storage of valuable information in synthetic DNA, protected with personalized keys. We show that genetic short tandem repeats (STRs) contain sufficient entropy to generate strong encryption keys, and that only one technology, DNA sequencing, is required to simultaneously read key and data. Using this approach, we experimentally generated 80 bit strong keys from human DNA, and used such a key to encrypt 17kB of digital information stored in synthetic DNA. Finally, the decrypted information was recovered perfectly from a single massively parallel sequencing run.