bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rostro-Caudal Specificity of Corticospinal Tract Projections in Mice
Authors: Steward Oswald , Yee Kelly M , Metcalfe Mariajose , Willenberg Rafer , Luo Juan , Azevedo Ricardo , Martin-Thompson Jacob H , Gandhi Sunil P 
Published: October 2020

Abstract
Rostro-caudal specificity of corticospinal tract (CST) projections from different areas of the cortex was assessed by retrograde labeling with fluorogold and retrograde transfection following retro-AAV/Cre injection into the spinal cord of tdT reporter mice. Injections at C5 led to retrograde labeling of neurons throughout forelimb area of the sensorimotor cortex and a region in the dorsolateral cortex near the barrel field (S2). Injections at L2 led to retrograde labeling of neurons in the posterior sensorimotor cortex (hindlimb area) but not the dorsolateral cortex. With injections of biotinylated dextran amine (BDA) into the main sensorimotor cortex (forelimb region), labeled axons terminated selectively at cervical levels. With BDA injections into caudal sensorimotor cortex (hindlimb region), labeled axons passed through cervical levels without sending collaterals into the gray matter and then elaborated terminal arbors at thoracic sacral levels. With BDA injections into the dorsolateral cortex near the barrel field, labeled axons terminated at high cervical levels. Axons from medial sensorimotor cortex terminated primarily in intermediate laminae and axons from lateral sensorimotor cortex terminated primarily in laminae III–V of the dorsal horn. One of the descending pathways seen in rats (the ventral CST) was not observed in most mice.
Diagnosis and Management of Intraabdominal Infection: Guidelines by the Chinese Society of Surgical Infection and Intensive Care and the Chinese College of Gastrointestinal Fistula Surgeons
Authors: Wu Xiuwen , Wu Jie , Wang Peige , Fang Xueling , Yu Yunsong , Tang Jianguo , Xiao Yonghong , Wang Minggui , Li Shikuan , Zhang Yun , Hu Bijie , Ma Tao , Li Qiang , Wang Zhiming , Wu Anhua , Liu Chang , Dai Menghua , Ma Xiaochun , Yi Huimin , Kang Yan , Wang Daorong , Han Gang , Zhang Ping , Wang Jianzhong , Yuan Yufeng , Wang Dong , Wang Jian , Zhou Zheng , Ren Zeqiang , Liu Yuxiu , Guan Xiangdong , Ren Jianan 
Published: October 2020

AbstractThe Chinese guidelines for IAI presented here were developed by a panel that included experts from the fields of surgery, critical care, microbiology, infection control, pharmacology, and evidence-based medicine. All questions were structured in population, intervention, comparison, and outcomes format, and evidence profiles were generated. Recommendations were generated following the principles of the Grading of Recommendations Assessment, Development, and Evaluation system or Best Practice Statement (BPS), when applicable. The final guidelines include 45 graded recommendations and 17 BPSs, including the classification of disease severity, diagnosis, source control, antimicrobial therapy, microbiologic evaluation, nutritional therapy, other supportive therapies, diagnosis and management of specific IAIs, and recognition and management of source control failure. Recommendations on fluid resuscitation and organ support therapy could not be formulated and thus were not included. Accordingly, additional high-quality clinical studies should be performed in the future to address the clinicians’ concerns.
A New Specimen for Syphilis Diagnosis: Evidence by High Loads ofTreponema pallidumDNA in Saliva
Authors: Wang Cuini , Hu Zhixiang , Zheng Xin , Ye Meiping , Liao Chunjie , Shang Mengya , Gong Weiming , Guan Zhifang , Lu Haikong , Gu Xin , Shi Mei , Zhou Pingyu 
Published: October 2020

AbstractBackgroundDNA from many pathogens can be detected in saliva. However, the presence and quantity of Treponema pallidum DNA in patients with syphilis in saliva is unknown.Methods234 patients with syphilis with different stages and 30 volunteers were enrolled. Paired saliva and plasma samples were collected from all participants. Consecutive saliva samples from 9 patients were collected every 4 hours following treatment. Treponema pallidum DNA in samples was determined by nested polymerase chain reaction (PCR) and droplet digital PCR targeting polA and Tpp47.ResultsTreponema pallidum DNA detection rates in saliva and plasma were 31.0% (9/29) and 51.7% (15/29) in primary syphilis (P = .11), 87.5% (63/72) and 61.1% (44/72) in secondary syphilis (P &lt; .001), 25.6% (21/82) and 8.5% (7/82) in latent syphilis (P = .004), and 21.6% (11/51) and 5.9% (3/51) in symptomatic neurosyphilis (P = .021), respectively. Median (range) loads of Tpp47 and polA in saliva were 627 (0–101 200) and 726 (0–117 260) copies/mL, respectively, for patients with syphilis. In plasma, however, loads of Tpp47 and polA were low: medians (range) of 0 (0–149.6) and 0 (0–176) copies/mL, respectively. Loads of T. pallidum DNA in saliva during treatment fluctuated downward; the clearance time was positively correlated with the loads of T. pallidum DNA before treatment.ConclusionsCollection of saliva is noninvasive and convenient. The high loads of T. pallidum DNA in saliva and reduction after treatment indicated that saliva can be not only a diagnostic fluid for syphilis but also an indicator of therapeutic effectiveness.
International Progress, International Order, and the Liberal International Order
Authors: Barnett Michael 
Published: October 2020

Abstract
Most explanations for the crisis of the liberal order revolve around geopolitics, globalization, economic resentment fueling new forms of populism and nationalism, and Western states following their interests away from liberal values and institutions of their creation. But international orders are produced and legitimated by both material and spiritual forces. The spirit in liberalism is moral progress defined by practices of humanity. If the Liberal International Order (LIO) is in decline, then perhaps we should consider its moral foundations. Section “Introduction” briefly introduces the question of international order, categorizes international relations theories according to the mixture of consent and coercion, and how legitimacy often refers not only to the existing order but a vision of progress. This is particularly true of the liberal international order. Section “International Order, Legitimacy, and Progress” turns to the liberal international order, progress, and the possible spiritual decline of the liberal international order. After briefly considering the liberal in international liberalism and the late 20th-century emergence of the liberal international order, I argue that one reason for its declining moral foundations is because of the pronounced individualism that resides at the heart of the contemporary international order. In other words, the sources of decline are not exogenous but rather part of liberalism. The Conclusion asks: what is next? The conjunction of the decline of the LIO and COVID-19 has complicated the debate about the future international order, and much of the conversation hinges on whether and how the United States can recover from its self-destructive tendencies and China’s intentions. But where is the spirit of moral progress and humanity in this discussion?
B-Type Natriuretic Peptide Is Associated with Indices of Left Ventricular Dysfunction in Healthy Subjects from the General Population: The Akershus Cardiac Examination 1950 Study
Authors: Lyngbakken Magnus Nakrem , Kvisvik Brede , Aagaard Erika Nerdrum , Berge Trygve , Pervez Mohammad Osman , Brynildsen Jon , Tveit Arnljot , Steine Kjetil , Røsjø Helge , Omland Torbjørn 
Published: October 2020

Abstract

Background
Concentrations of B-type natriuretic peptide (BNP) reflect myocardial distension and stress, and are associated with poor prognosis in patients with cardiovascular disease. Accordingly, we hypothesized that concentrations of BNP would be associated with indices of adverse left ventricular (LV) remodeling and early stages of LV systolic and diastolic dysfunction in healthy participants from the general population.

Methods
We measured BNP in 1757 women and 1677 men free from known coronary heart disease participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants underwent extensive cardiovascular phenotyping at baseline, including detailed echocardiography with assessment of indexed LV mass (LVMI), diastolic [tissue Doppler e’, E/e’ ratio, indexed left atrial volume (LAVI), maximal tricuspid regurgitation velocity (TRVmax), and E/A ratio], and systolic [global longitudinal strain (GLS) and LV ejection fraction (LVEF)] function.

Results
Study participants with the highest BNP concentrations had higher GLS, LVMI, e’, E/e’ ratio, LAVI, TRVmax, and E/A ratio. In adjusted analyses, both GLS and LVEF exhibited significant nonlinear associations with BNP, with reduced LV systolic function observed in both the low and high concentration range of BNP.

Conclusions
In healthy participants recruited from the general population, concentrations of BNP exhibit nonlinear associations with LV systolic function, and both low and high concentrations are associated with reduced LV systolic function. This supports the notion that natriuretic peptides are beneficial and elicit cardioprotective effects, and may have important implications for the interpretation of BNP measurements in the general population.
Off-target effects of sodium-glucose co-transporter 2 blockers: empagliflozin does not inhibit Na+/H+ exchanger-1 or lower [Na+]i in the heart
Authors: Chung Yu Jin , Park Kyung Chan , Tokar Sergiy , Eykyn Thomas R , Fuller William , Pavlovic Davor , Swietach Pawel , Shattock Michael J 
Published: October 2020

Abstract

Aims
Emipagliflozin (EMPA) is a potent inhibitor of the renal sodium-glucose co-transporter 2 (SGLT2) and an effective treatment for type-2 diabetes. In patients with diabetes and heart failure, EMPA has cardioprotective effects independent of improved glycaemic control, despite SGLT2 not being expressed in the heart. A number of non-canonical mechanisms have been proposed to explain these cardiac effects, most notably an inhibitory action on cardiac Na+/H+ exchanger 1 (NHE1), causing a reduction in intracellular [Na+] ([Na+]i). However, at resting intracellular pH (pHi), NHE1 activity is very low and its pharmacological inhibition is not expected to meaningfully alter steady-state [Na+]i. We re-evaluate this putative EMPA target by measuring cardiac NHE1 activity.

Methods and results
The effect of EMPA on NHE1 activity was tested in isolated rat ventricular cardiomyocytes from measurements of pHi recovery following an ammonium pre-pulse manoeuvre, using cSNARF1 fluorescence imaging. Whereas 10 µM cariporide produced near-complete inhibition, there was no evidence for NHE1 inhibition with EMPA treatment (1, 3, 10, or 30 µM). Intracellular acidification by acetate-superfusion evoked NHE1 activity and raised [Na+]i, reported by sodium binding benzofuran isophthalate (SBFI) fluorescence, but EMPA did not ablate this rise. EMPA (10 µM) also had no significant effect on the rate of cytoplasmic [Na+]i rise upon superfusion of Na+-depleted cells with Na+-containing buffers. In Langendorff-perfused mouse, rat and guinea pig hearts, EMPA did not affect [Na+]i at baseline nor pHi recovery following acute acidosis, as measured by 23Na triple quantum filtered NMR and 31P NMR, respectively.

Conclusions
Our findings indicate that cardiac NHE1 activity is not inhibited by EMPA (or other SGLT2i’s) and EMPA has no effect on [Na+]i over a wide range of concentrations, including the therapeutic dose. Thus, the beneficial effects of SGLT2i’s in failing hearts should not be interpreted in terms of actions on myocardial NHE1 or intracellular [Na+].
TopoDB: a novel multifunctional management system for laboratory animal colonies
Authors: Renschen Adam , Matsunaga Atsuko , Oksenberg Jorge R , Santaniello Adam , Didonna Alessandro 
Published: October 2020

Abstract
Animal models are widely employed in basic research to test mechanistic hypotheses in a complex biological environment as well as to evaluate the therapeutic potential of candidate compounds in preclinical settings. Rodents, and in particular mice, represent the most common in vivo models for their small size, short lifespan and possibility to manipulate their genome. Over time, a typical laboratory will develop a substantial number of inbred strains and transgenic mouse lines, requiring a substantial effort, in both logistic and economic terms, to maintain an animal colony for research purposes and to safeguard the integrity of results. To meet this need, here we present TopoDB, a robust and extensible web-based platform for the rational management of laboratory animals. TopoDB allows an easy tracking of individual animals within the colony and breeding protocols as well as the convenient storage of both genetic and phenotypic data generated in the different experiments. Altogether, these features facilitate and enhance the design of in vivo research, thus reducing the number of necessary animals and the housing costs. In summary, TopoDB represents a novel valuable tool in modern biomedical research.
Database URL: https://github.com/UCSF-MS-DCC/TopoDB
Continuation of Anti-TNF in Patients With Ulcerative Colitis in Remission Is Not Cost-effective Compared With Treatment Withdrawal: A Markov Model
Authors: Mahmoud Remi , van Lieshout Chris , Frederix Geert W J , Jharap Bindia , Oldenburg Bas 
Published: October 2020

Abstract

Background and Aims
Anti-tumour necrosis factor alpha [anti-TNF] treatment accounts for 31% of health care expenditures associated with ulcerative colitis [UC]. Withdrawal of anti-TNF in patients with UC in remission may decrease side effects and infections, while promoting cost containment. Approximately 36% of patients relapse within 12–24 months of anti-TNF withdrawal, but reintroduction of treatment is successful in 80% of patients. We aimed to evaluate the cost-effectiveness of continuation versus withdrawal of anti-TNF in patients with UC in remission.

Methods
We developed a Markov model comparing cost-effectiveness of anti-TNF continuation versus withdrawal, from a health care provider perspective. Transition probabilities were calculated from literature, or estimated by an expert panel of 11 gastroenterologists. Deterministic and probabilistic sensitivity analyses were performed to account for assumptions and uncertainty. The cost-effectiveness threshold was set at an incremental cost-effectiveness ratio of €80,000 per quality-adjusted life-year [QALY].

Results
At 5 years, anti-TNF withdrawal was less costly [-€10,781 per patient], but also slightly less effective [-0.04 QALY per patient] than continued treatment. Continuation of anti-TNF compared with withdrawal costs €300,390/QALY, exceeding the cost-effectiveness threshold. Continued therapy would become cost-effective if the relapse rate following anti-TNF withdrawal was ≥43% higher, or if adalimumab or infliximab [biosimilar] prices fell below €87/40 mg and €66/100 mg, respectively.

Conclusions
Continuation of anti-TNF in UC patients in remission is not cost-effective compared with withdrawal. A stop-and-reintroduction strategy is cost-saving but is slightly less effective than continued therapy. This strategy could be improved by identifying patients at increased risk of relapse.
Screening for texturing Leuconostoc and genomics behind polysaccharide production
Authors: Poulsen Vera Kuzina , Koza Anna , Al-Nakeeb Kosai , Oeregaard Gunnar 
Published: October 2020

ABSTRACT
Synthesis of polysaccharides by Leuconostoc can result in improved texture of fermented products. A total of 249 Leuconostoc strains were screened for homo-polysaccharide production and for texturing capabilities in milk. A total of six Ln. mesenteroides strains with superior texturing properties had the genetic blueprint for both homo- (HoPS) and hetero-polysaccharide (HePS) synthesis. Only one strain produced texture in milk without added sucrose, suggesting HePS synthesis via the Wzy dependent pathway. In milk acidification experiments with added sucrose, all six strains depleted the sucrose and released fructose. Thus, they can be used for both texture and possibly also for sweetness enhancement.
Development of a common scale for measuring healthy ageing across the world: results from the ATHLOS consortium
Authors: Sanchez-Niubo Albert , Forero Carlos G , Wu Yu-Tzu , Giné-Vázquez Iago , Prina Matthew , De La Fuente Javier , Daskalopoulou Christina , Critselis Elena , De La Torre-Luque Alejandro , Panagiotakos Demosthenes , Arndt Holger , Ayuso-Mateos José Luis , Bayes-Marin Ivet , Bickenbach Jerome , Bobak Martin , Caballero Francisco Félix , Chatterji Somnath , Egea-Cortés Laia , García-Esquinas Esther , Leonardi Matilde , Koskinen Seppo , Koupil Ilona , Mellor-Marsá Blanca , Olaya Beatriz , Pająk Andrzej , Prince Martin , Raggi Alberto , Rodríguez-Artalejo Fernando , Sanderson Warren , Scherbov Sergei , Tamosiunas Abdonas , Tobias-Adamczyk Beata , Tyrovolas Stefanos , Haro Josep Maria ,   the ATHLOS Consortium
Published: October 2020

Abstract

Background
Research efforts to measure the concept of healthy ageing have been diverse and limited to specific populations. This diversity limits the potential to compare healthy ageing across countries and/or populations. In this study, we developed a novel measurement scale of healthy ageing using worldwide cohorts.

Methods
In the Ageing Trajectories of Health-Longitudinal Opportunities and Synergies (ATHLOS) project, data from 16 international cohorts were harmonized. Using ATHLOS data, an item response theory (IRT) model was used to develop a scale with 41 items related to health and functioning. Measurement heterogeneity due to intra-dataset specificities was detected, applying differential item functioning via a logistic regression framework. The model accounted for specificities in model parameters by introducing cohort-specific parameters that rescaled scores to the main scale, using an equating procedure. Final scores were estimated for all individuals and converted to T-scores with a mean of 50 and a standard deviation of 10.

Results
A common scale was created for 343 915 individuals above 18 years of age from 16 studies. The scale showed solid evidence of concurrent validity regarding various sociodemographic, life and health factors, and convergent validity with healthy life expectancy (r = 0.81) and gross domestic product (r = 0.58). Survival curves showed that the scale could also be predictive of mortality.

Conclusions
The ATHLOS scale, due to its reliability and global representativeness, has the potential to contribute to worldwide research on healthy ageing.
The Block-and-Lock Strategy for Human Immunodeficiency Virus Cure: Lessons Learned from Didehydro–Cortistatin A
Authors: Li Chuan , Mori Luisa , Valente Susana T 
Published: October 2020

Abstract
Antiretroviral therapy effectively controls human immunodeficiency virus (HIV) infection. However, a reservoir of latently infected cells persists under suppressive therapy, constituting a major barrier to an HIV cure. The block-and-lock approach to a functional cure aims at the transcriptional and epigenetic silencing of proviruses, blocking viral reactivation in the absence of therapy, preventing disease progression and transmission, despite the presence of detectable integrated proviruses. This approach has been put forward for exploration based on the activity of didehydro–cortistatin A, an inhibitor of the HIV transcriptional activator Tat. Here we review the mechanisms by which didehydro–cortistatin A inhibition of Tat’s feedback loop transcriptional amplification results in epigenetic silencing of the HIV promoter, and we discuss the benefits and limitations of the block-and-lock approach for an HIV cure.
Implementation of a learning healthcare system for sickle cell disease
Authors: Miller Robin , Coyne Erin , Crowgey Erin L , Eckrich Dan , Myers Jeffrey C , Villanueva Raymond , Wadman Jean , Jacobs-Allen Sidnie , Gresh Renee , Volchenboum Samuel L , Kolb E Anders 
Published: October 2020

ABSTRCTObjectiveUsing sickle cell disease (SCD) as a model, the objective of this study was to create a comprehensive learning healthcare system to support disease management and research. A multidisciplinary team developed a SCD clinical data dictionary to standardize bedside data entry and inform a scalable environment capable of converting complex electronic healthcare records (EHRs) into knowledge accessible in real time.Materials and MethodsClinicians expert in SCD care developed a data dictionary to describe important SCD-associated health maintenance and adverse events. The SCD data dictionary was deployed in the EHR using EPIC SmartForms, an efficient bedside data entry tool. Additional data elements were extracted from the EHR database (Clarity) using Pentaho Data Integration and stored in a data analytics database (SQL). A custom application, the Sickle Cell Knowledgebase, was developed to improve data analysis and visualization. Utilization, accuracy, and completeness of data entry were assessed.ResultsThe SCD Knowledgebase facilitates generation of patient-level and aggregate data visualization, driving the translation of data into knowledge that can impact care. A single patient can be selected to monitor health maintenance, comorbidities, adverse event frequency and severity, and medication dosing/adherence.ConclusionsDisease-specific data dictionaries used at the bedside will ultimately increase the meaningful use of EHR datasets to drive consistent clinical data entry, improve data accuracy, and support analytics that will facilitate quality improvement and research.