Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparing individual-based approaches to modelling the self-organization of multicellular tissues

The coordinated behaviour of populations of cells plays a central role in tissue growth and renewal. Cells react to their microenvironment by modulating processes such as movement, growth and proliferation, and signalling. Alongside experimental studies, computational models offer a useful means by which to investigate these processes. To this end a variety of cell-based modelling approaches have been developed, ranging from lattice-based cellular automata to lattice-free models that treat cells as point-like particles or extended shapes. It is difficult to accurately compare between different modelling approaches, since one cannot distinguish between differences in behaviour due to the underlying model assumptions and those due to differences in the numerical implementation of the model. Here, we exploit the availability of an implementation of five popular cell-based modelling approaches within a consistent computational framework, Chaste (http://www.cs.ox.ac.uk/chaste). This framework allows one to easily change constitutive assumptions within these models. In each case we provide full details of all technical aspects of our model implementations. We compare model implementations using four case studies, chosen to reflect the key cellular processes of proliferation, adhesion, and short-and long-range signalling. These case studies demonstrate the applicability of each model and provide a guide for model usage. Authors’ contributions JO and AF conceived of the study, designed the study, coordinated the study, carried out the computational modelling and drafted the manuscript. JP contributed to the computational modelling and helped draft the manuscript. PM and DG conceived of the study, designed the study and helped draft the manuscript. All authors gave final approval for publication.
Epithelial to mesenchymal transition during gastrulation: An embryological view

Gastrulation is a developmental process to generate the mesoderm and endoderm from the ectoderm, of which the epithelial to mesenchymal transition (EMT) is generally considered to be a critical component. Due to increasing evidence for the involvement of EMT in cancer biology, a renewed interest is seen in using in vivo models, such as gastrulation, for studying molecular mechanisms underlying EMT. The intersection of EMT and gastrulation research promises novel mechanistic insight, but also creates some confusion. Here we discuss, from an embryological perspective, the involvement of EMT in mesoderm formation during gastrulation in triploblastic animals. Both gastrulation and EMT exhibit remarkable variations in different organisms, and no conserved role for EMT during gastrulation is evident. We propose that a ‘broken‐down’ model, in which these two processes are considered to be a collective sum of separately regulated steps, may provide a better framework for studying molecular mechanisms of the EMT process in gastrulation, and in other developmental and pathological settings.
The Impact of Intimate Partner Violence Exposure in Adolescence and Emerging Adulthood: A Developmental Psychopathology Approach

Despite increased attention on parental intimate partner violence (IPV) exposure, a relative paucity of research has examined the developmental consequences of this traumatic experience within a life span approach. The aim of the present study was to examine how parental IPV exposure may relate to mental health during the transition from adolescence to emerging adulthood. Furthermore, we examined whether the impact of parental IPV exposure was unique from more commonly studied maltreatment experiences, specifically neglect and physical abuse. A large, racially and ethnically diverse sample (Nbaseline = 1,042; 56% female; Mage = 15.1, SD = 0.79; 31.4% Hispanic, 29.4% White, 27.9% African American, 3.6% Asian, 7.7% biracial or other) of adolescents completed a baseline assessment for parental physical IPV exposure and maltreatment as well as measures for symptoms of depression, posttraumatic stress, and substance use, annually for 6 consecutive years. Mixed-level modeling was used to examine how parental IPV exposure was uniquely associated with different patterns of mental health across developmental epochs. Findings demonstrated a multifaceted relation with mental health. For internalizing symptoms, the effect was pronounced during adolescence, and neglect increased the risk for depression symptomatology. Meanwhile, parental-IPV-exposed adolescents were at increasing risk for substance use as they aged into adulthood. Symptom levels and trajectories were independent and distinct from maltreatment experiences. This study helps illuminate parental IPV exposure’s unique influence on well-being during vulnerable developmental periods. It also calls attention to the importance of developing suitable intervention/prevention programs to target this vulnerable population.
First record and genetic affiliation of the Balkan Snow Vole Dinaromys bogdanovi (Rodentia: Cricetidae) in Albania

One individual of the rare rodent Dinaromys bogdanovi (Martino, 1922) was trapped in Prokletije Mountains, northern Albania. This is the first record of this species in Albania, and morphological data and genetic affiliation are presented. Analysis of mitochondrial DNA (cytochrome b ) places this individual within the reported central phylogenetic lineage of the species. This first record has impacts for future conservation activities.
Automatic Status Updates in Exacts Global Development Process

Due to a competitive business environment and demanding customers, many companies turn to globally distributed software development and agile methodologies. Globally distributed software engineering can bring great advantages in reducing costs, reducing time to market, and give access to a larger pool of skilled resources. Agile methodologies acknowledge many of the development challenges companies face, such as changing customers requirements and the necessity to have frequent releases. Introducing agile by itself can be a challenge for a big organization, especially when a blend is made between agile and distributed development, since these have some contradictory features. The global company Exact faces some challenges when introducing agility into its business processes. This research has as a goal to introduce agile into the globally distributed development process of Exact. It is hard to introduce agile as a whole, therefore we address the biggest challenges faced within Exacts development process first. One of the main challenges faced within Exact is communication between the globally dispersed product management and product development teams. An agile practice addressing this communication challenge is to use automatic status updates and product updates generated by an automated build process. This research will explore what features of continuous integration are useful for Exact and the created system will be evaluated. The ideas presented in this thesis have not yet been tested and evaluated on a large scale, due to time restrictions. However a prototype has been tested on a small scale for one project, and the initial responses from product development and product management were positive. More important, a shift in perception occurred at product development to support a more open development process.
CYP2J2 and its metabolites (epoxyeicosatrienoic acids) attenuate cardiac hypertrophy by activating AMPKα2 and enhancing nuclear translocation of Akt1

Cytochrome P450 epoyxgenase 2J2 and epoxyeicosatrienoic acids (EETs) are known to protect against cardiac hypertrophy and heart failure, which involve the activation of 5′‐AMP‐activated protein kinase (AMPK) and Akt. Although the functional roles of AMPK and Akt are well established, the significance of cross talk between them in the development of cardiac hypertrophy and antihypertrophy of CYP2J2 and EETs remains unclear. We investigated whether CYP2J2 and its metabolites EETs protected against cardiac hypertrophy by activating AMPKα2 and Akt1. Moreover, we tested whether EETs enhanced cross talk between AMPKα2 and phosphorylated Akt1 (p‐Akt1), and stimulated nuclear translocation of p‐Akt1, to exert their antihypertrophic effects. AMPKα2−/− mice that overexpressed CYP2J2 in heart were treated with Ang II for 2 weeks. Interestingly, overexpression of CYP2J2 suppressed cardiac hypertrophy and increased levels of atrial natriuretic peptide (ANP) in the heart tissue and plasma of wild‐type mice but not AMPKα2−/− mice. The CYP2J2 metabolites, 11,12‐EET, activated AMPKα2 to induce nuclear translocation of p‐Akt1 selectively, which increased the production of ANP and therefore inhibited the development of cardiac hypertrophy. Furthermore, by co‐immunoprecipitation analysis, we found that AMPKα2β2γ1 and p‐Akt1 interact through the direct binding of the AMPKγ1 subunit to the Akt1 protein kinase domain. This interaction was enhanced by 11,12‐EET. Our studies reveal a novel mechanism in which CYP2J2 and EETs enhanced Akt1 nuclear translocation through interaction with AMPKα2β2γ1 and protect against cardiac hypertrophy and suggest that overexpression of CYP2J2 might have clinical potential to suppress cardiac hypertrophy and heart failure.
Using Time-Driven Activity-Based Costing as a Key Component of the Value Platform: A Pilot Analysis of Colonoscopy, Aortic Valve Replacement and Carpal Tunnel Release Procedures

Background Time-driven activity-based costing (TDABC) is a methodology that calculates the costs of healthcare resources consumed as a patient moves along a care process. Limited data exist on the application of TDABC from the perspective of an anesthesia provider. We describe the use of TDABC, a bottom-up costing strategy and financial outcomes for three different medical-surgical procedures. Methods In each case, a multi-disciplinary team created process maps describing the care delivery cycle for a patient encounter using the TDABC methodology. Each step in a process map delineated an activity required for delivery of patient care. The resources (personnel, equipment and supplies) associated with each step were identified. A per minute cost for each resource expended was generated, known as the capacity cost rate, and multiplied by its time requirement. The total cost for an episode of care was obtained by adding the cost of each individual resource consumed as the patient moved along a clinical pathway. Results We built process maps for colonoscopy in the gastroenterology suite, calculated costs of an aortic valve replacement by comparing surgical aortic valve replacement (SAVR) versus transcatheter aortic valve replacement (TAVR) techniques, and determined the cost of carpal tunnel release in an operating room versus an ambulatory procedure room. Conclusions TDABC is central to the value-based healthcare platform. Application of TDABC provides a framework to identify process improvements for health care delivery. The first case demonstrates cost-savings and improved wait times by shifting some of the colonoscopies scheduled with an anesthesiologist from the main hospital to the ambulatory facility. In the second case, we show that the deployment of an aortic valve via the transcatheter route front loads the costs compared to traditional, surgical replacement. The last case demonstrates significant cost savings to the healthcare system associated with re-organization of staff required to execute a carpal tunnel release.
Connectivity, prison environment and mental health among first-time male inmates in Mexico City

ABSTRACT Research from high-income countries suggests that prison populations are affected disproportionately by mental illness. However, little research has examined mental health among prisoners in low- and middle-income countries or associations between mental health and contextual factors surrounding the prison experience among susceptible first-time inmates in these settings. The current study examines associations between connectivity, prison environment and mental health (major depression and substance use) among novice male inmates (n = 593) in three Mexico City prisons. Severe depression (46.2%), any substance use (53.8%) and heavy substance use (45.7%) were prevalent. Among key co-variates, recent visitors were protective for severe depression, conjugal visits for any substance use and prison employment for heavy substance use. Physical attacks were associated with increased prevalence of depression, sentence time served with both any and heavy substance use and overcrowding with any substance use. These findings suggest the need for routine health assessments to improve identification and treatment programmes to minimise mental health burden. Addressing demographic risk factors as well as contextual determinants, by decreasing physical violence and overcrowding and supporting outside connections for prisoners, may help improve inmate mental health.
Novel mcr-3 variant, encoding mobile colistin resistance, in an ST131 Escherichia coli isolate from bloodstream infection, Denmark, 2014

A novel variant of the plasmid-borne colistin resistance gene mcr-3 was detected on an IncHI2 plasmid in an ST131 CTX-M-55-producing Escherichia coli isolate from a Danish patient with bloodstream infection in 2014. The discovery of novel plasmid-borne genes conferring resistance to colistin is of special interest since colistin has reemerged as an important drug in the treatment of infections with multidrug-resistant Gram-negative bacteria.
Adult granulosa cell tumors of the ovary: a retrospective study of 30 cases with respect to the expression of steroid synthesis enzymes

Objective Some, but not all, granulosa cell tumors are characterized by estrogen production. This study was designed to determine whether there are clinical or pathological variations in granulosa cell tumors in relation to the expression of sex steroid synthesis enzymes. Methods Clinical symptoms, serum hormonal values, and histology of 30 granulosa cell tumor patients who underwent surgery between 2002 and 2014 were retrospectively reviewed. Results Most patients presented with abnormal genital bleeding including abnormal menstrual cycles. Eight of 16 patients older than 50 years had endometrial hyperplasia and one had endometrial cancer. Serum 17β-estradiol (E2) levels tended to be higher in patients over 50 years of age (p=0.081). Serum follicle-stimulating hormone (FSH) levels were low in all patients irrespective of serum E2 levels. Magnetic resonance imaging revealed a thicker endometrium in older as compared to younger patients (p<0.05). Tumor cells in the majority of cases were positive for inhibin α and P450 aromatase, irrespective of age and serum E2 levels. P450 17α-hydroxylase (P450c17) expression varied among cases. P450c17 was strongly positive in luteinized tumor cells and weakly positive in theca cells and fibroblasts. High E2 levels were associated with P450c17-positive cells in the tumor (p<0.05). Conclusion The expression of hormone-synthesizing enzymes divides granulosa cell tumors into 2 distinct types; tumors with P450c17-positive cells show elevated serum E2 and related clinical symptoms, while tumors without these cells show symptoms related to FSH suppression by inhibin.
Tolerance Does Not Develop Toward Liraglutide’s Glucose-Lowering Effect

Context Glucagon-like peptide-1 receptor agonists are popular antidiabetic drugs with potent glucose-lowering effects and low risk of hypoglycemia. Animal experiments and human data indicate that tolerance develops toward at least some of their effects (e.g., gastric motility). Whether tolerance develops toward the glucose-lowering effect of glucagon-like peptide-1 receptor agonists has never been formally tested. Objective The objective of this pilot study was to test the hypothesis whether tolerance develops toward glucagon-like peptide-1 receptor agonists' glucose-lowering effect in chronic use. Design, Setting, Participants, and Intervention We conducted a single group, open-label clinical trial. Ten healthy volunteers were treated with 0.6 mg liraglutide once daily subcutaneously for 21 days. The drug's effect was quantified by serial graded glucose infusion tests, with glucose and c-peptide measured every 20 minutes and insulin secretion rate calculated. Main Outcome Measure The primary outcome was a change in the dose-response relationship between calculated insulin secretion rate and blood glucose level after acute and chronic administration of liraglutide. Results Liraglutide clearly decreased the glucose values during the graded glucose infusion test and robustly enhanced insulin secretion. For all parameters, chronic liraglutide was as effective as acute treatment in human subjects. Conclusions We conclude that our results largely refute the hypothesis of tolerance development with prolonged liraglutide use in healthy nonobese humans.
Good Distance Lattices from High Dimensional Expanders

We show a new framework for constructing good distance lattices from high dimensional expanders. For error-correcting codes, which have a similar flavor as lattices, there is a known framework that yields good codes from expanders. However, prior to our work, there has been no framework that yields good distance lattices directly from expanders. Interestingly, we need the notion of high dimensional expansion (and not only one dimensional expansion) for obtaining large distance lattices which are dense. Our construction is obtained by proving the existence of bounded degree high dimensional cosystolic expanders over any ring, and in particular over $\mathbb{Z}$. Previous bounded degree cosystolic expanders were known only over $\mathbb{F}_2$. The proof of the cosystolic expansion over any ring is composed of two main steps, each of an independent interest: We show that coboundary expansion over any ring of the links of a bounded degree complex implies that the complex is a cosystolic expander over any ring. We then prove that all the links of Ramanujan complexes (which are called spherical buildings) are coboundary expanders over any ring. We follow the strategy of [LMM16] for proving that the spherical building is a coboundary expander over any ring. Besides of generalizing their proof from $\mathbb{F}_2$ to any ring, we present it in a detailed way, which might serve readers with less background who wish to get into the field.
Effects of Switching to the Menthol Tobacco Heating System 2.2, Smoking Abstinence, or Continued Cigarette Smoking on Clinically Relevant Risk Markers: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 2)

Abstract Introduction Modified-risk tobacco products are expected to reduce exposure to harmful and potentially harmful constituents of cigarette smoke, and ultimately reduce the health burden of smoking-related diseases. Clinically relevant risk markers of smoking-related diseases inform about the risk profile of new tobacco products in the absence of in-market epidemiological data. The menthol Tobacco Heating System 2.2 (mTHS) is a modified-risk tobacco product in development as an alternative to cigarettes (conventional cigarettes [CCs]). Methods In this parallel-group study, Japanese adult smokers (23–65 years; ≥10 mCCs/day) were randomized to mTHS, menthol CCs (mCC), or smoking abstinence (SA) for 5 days in confinement and 85 days in ambulatory settings. Endpoints included biomarkers of exposure to harmful and potentially harmful constituents and clinically relevant risk markers of smoking-related diseases. Results One-hundred and sixty participants were randomized to the mTHS (n = 78), mCC (n = 42), and SA (n = 40) groups. Switching to the mTHS was associated with reductions in biomarkers of exposure compared with continuing mCCs. Reductions in 8-epi-prostaglandin F2α (biomarker of oxidative stress), 11-dehydro-thromboxane B2 (biomarker of platelet activation), soluble intracellular adhesion molecule-1 (biomarker of endothelial function), and an increase in high-density lipoprotein cholesterol (biomarker of lipid metabolism) and forced expiratory volume in 1 second (biomarker of lung function) occurred in the mTHS group compared with the mCC group. The changes in the mTHS group approached those in the SA group. Conclusions Switching from mCCs to mTHS was associated with improvements in clinically relevant risk markers linked to mechanistic pathways involved in smoking-related diseases. Implications In this three-way randomized study, switching from menthol cigarettes to mTHS for 5 days in confinement and 85 days in ambulatory settings was associated with reductions in biomarkers of exposure to cigarette smoke, and changes were observed in clinically relevant biomarkers of oxidative stress (8-epi-prostaglandin F2α), platelet activity (11-dehydro-thromboxane B2), endothelial function (soluble intracellular adhesion molecule-1), lipid metabolism (high-density lipoprotein cholesterol) and lung function (forced expiratory volume in 1 second), similar to the SA group. The results suggest that switching to the mTHS has the potential to reduce the adverse health effects of conventional cigarettes.
Reduced Rapid Eye Movement Density in Parkinson Disease: A Polysomnography-Based Case-Control Study.

STUDY OBJECTIVES To explore rapid eye movement density (RD) in patients with idiopathic Parkinson disease (IPD) and to investigate its usefulness as surrogate marker of excessive daytime sleepiness, a frequent complaint in IPD patients. METHODS Retrospective polysomnography study on 81 subjects without dementia: 29 patients with early stage IPD (disease duration ≤ 3 y), 21 patients with middle- stage IPD (disease duration > 3 and < 8 y) and 31 healthy controls (HC). Rapid eye movement (REM) sleep was defined as any REM episode with > 3 min of continuous REM sleep. RD was defined as number of ocular movements per minute of REM sleep. Patients with early stage IPD and HC fulfilled the PD-specific sleepiness questionnaires Parkinson's Disease Sleep Scale (PDSS) and the Nonmotor Symptoms Questionnaire for Parkinson's disease (NMSQuest). RESULTS RD was lower in patients with IPD than in HC. The difference was most significant between patients with middle stage IPD and HC (P = 0.001), and most prominent for the third REM episode, again when comparing patients with middle stage IPD and HC (P = 0.03). RD was independent from sex, age, and other sleep parameters. In early stage IPD, RD correlated with the PDSS score (r = -0.63, P = 0.001) and the sleep-related questions of the NMSQuest score (r = 0.48, P = 0.017). CONCLUSIONS REM density is reduced in patients with IPD and correlates with subjective scores on sleep impairment. As an indicator of persistent high sleep pressure, reduced RD in IPD is eligible as a biomarker of excessive daytime sleepiness in IPD. It possibly reflects direct involvement of the brainstem REM generation sites by the disease process. RD is a promising new tool for sleep research in IPD.
How Do Programmers Maintain Concurrent Code?

Concurrent programming is pervasive in nowadays software development. Many programmers believe that concurrent programming is difficult, and maintaining concurrency code is error-prone. Although researchers have conducted empirical studies to understand concurrent programming, they still rarely study how programmers maintain concurrent code. To the best of our knowledge, only a recent study explored the modifications on critical sections, and many related questions are still open. In this paper, we conduct an empirical study to explore how programmers maintain concurrent code. We analyze more concurrency-related commits and explore more issues such as the change patterns of maintaining concurrent code than the previous study. We summarize five change patterns according to our analysis on 696 concurrency-related commits. We apply our change patterns to three open source projects, and synthesize three pull requests. Until now, two of them have been accepted. Our results can be useful for programmers to maintain concurrent code and for researchers to implement treating techniques.