Miracle-dz/UniFAR-FTUs huggingface dataset:
How Often Do Protein Genes Navigate Valleys of Low Fitness?

In order escape from local fitness peaks, a population must navigate across valleys of low fitness. How these transitions occur, and what role they play in adaptation, have been subjects of active interest in evolutionary genetics for almost a century. However, to our knowledge, this problem has never been addressed directly, by considering the evolution of a gene, or group of genes, as a whole, including the complex effects of fitness interactions among multiple loci. Here, we use a precise model of protein fitness to compute the probability P(s, Δt) that an allele, randomly sampled from a population at time t, has crossed a fitness valley of depth s during an interval [t − Δt, t] in the immediate past. We study populations of model genes evolving under equilibrium conditions consistent with those in mammalian mitochondria. From this data, we estimate that genes encoding small protein motifs navigate fitness valleys of depth 2Ns ≳ 30 with probability P ≳ 0.1 on a time scale of human evolution, where N is the (mitochondrial) effective population size. The results are consistent with recent findings for Watson–Crick switching in mammalian mitochondrial tRNA molecules.
Effect of Inflammation on the Process of Stroke Rehabilitation and Poststroke Depression

A considerable body of evidence has shown that inflammation plays an important role in the process of stroke rehabilitation and development of poststroke depression (PSD). However, the specific molecular and cellular mechanisms involved remain unclear. In this review, we summarize how neuroinflammation affects stroke rehabilitation and PSD. We mainly focus on the immune/inflammatory response, involving astrocytes, microglia, monocyte-derived macrophages, cytokines (tumor necrosis factor alpha, interleukin 1), and microRNAs (microRNA-124, microRNA 133b). This review provides new insights into the effect of inflammation on the process of stroke rehabilitation and PSD and potentially offer new therapeutic targets of stroke and PSD.
Effectiveness of Structural–Strategic Family Therapy in the Treatment of Adolescents with Mental Health Problems and Their Families

Mental health problems during adolescence constitute a major public health concern today for both families and stakeholders. Accordingly, different family-based interventions have emerged as an effective treatment for adolescents with certain disorders. Specifically, there is evidence of the effectiveness of concrete approaches of systemic family therapy on the symptoms of adolescents and family functioning in general. However, few studies have examined the effectiveness of other relevant approaches, such as structural and strategic family therapy, incorporating parent–child or parental dyadic measurement. The purpose of this study was to test the effectiveness of a structural–strategic family therapy with adolescents involved in mental health services and their families. For this purpose, 41 parents and adolescents who participated in this treatment were interviewed at pre-test and post-test, providing information on adolescent behavior problems, parental sense of competence, parental practices, parenting alliance, and family functioning. Regardless of participants’ gender, adolescents exhibited fewer internalizing and externalizing problems after the treatment. Parents reported higher family cohesion, higher satisfaction and perceived efficacy as a parent, and healthier parental practices (less authoritarian and permissive practices, as well as more authoritative ones). An interaction effect between parenting alliance and gender was found, with more favorable results for the mothers. In conclusion, this paper provides evidence of the usefulness of structural–strategic family therapy for improving family, dyadic, and individual facets in families with adolescents exhibiting mental health problems.
Genetic diversity and population structure of early-maturing tropical maize inbred lines using SNP markers

Information on genetic diversity and population structure are very important in any breeding programme for the improvement of traits of interest and the development of outstanding products for commercialization. In the present study, we assessed the genetic diversity of 94 early-maturing white and yellow tropical maize inbred lines using single nucleotide polymorphism (SNP) markers. The larger number of SNP markers used in this study allowed a clearer inference of the population structure of the 94 inbred lines. Cluster analysis resolved the inbred lines into different clusters based on their pedigree, selection history and endosperm colour. However, three heterotic groups were revealed by population structure analysis, but additional field evaluation could be more informative to confirm the heterotic groups identified. Nevertheless, wide genetic variability existed among the inbred lines making them unique with the potential to contribute new beneficial alleles to maize breeding programmes in the tropics, especially in the West and Central Africa (WCA) sub-region.
Deficient Explicit Access to Phonological Representations Explains Phonological Fluency Difficulties in Greek Children With Dyslexia and/or Developmental Language Disorder

It is well-established that children with dyslexia and/or Developmental Language Disorder (hereafter children with DDLD) perform poorly on phonological tasks compared to typically developing (TD) children. However, there has been some debate as to whether their phonological deficit arises directly from an impairment in phonological representations, or instead from deficient access to (intact) phonological representations. This study tested the Degraded Phonological Representations Hypothesis and the Deficient Phonological Access Hypothesis using a task that is not often used with children with DDLD, namely phonological fluency. Both hypotheses predict that children with DDLD will retrieve fewer items than their TD peers in the phonological fluency task. However, while the Degraded Phonological Representations Hypothesis predicts smaller clusters of phonologically related items in children with DDLD, the Deficient Phonological Access Hypothesis predicts that the two groups will not differ in cluster size. How phonological fluency performance related to children’s language, literacy, and phonological skills was investigated. Further, the specificity of a phonological fluency deficit in children with DDLD was tested using a nonverbal (design) fluency task. Sixty-six children with DDLD aged 7–12 years and 83 TD children aged 6–12 years, all monolingual Greek speakers, were tested on three phonological fluency categories, on nonverbal IQ, language, literacy, and phonological tasks, and on a design fluency task. The DDLD group produced significantly fewer correct responses and fewer switches compared to the TD group, but the two groups showed similar clustering and average cluster size. After controlling for age, children’s language, literacy, and phonological skills significantly predicted the number of correct responses produced. The two groups did not differ significantly on the number of unique designs generated in the design fluency task. Furthermore, children with DDLD showed poorer phonological fluency performance relative to their TD peers even after design fluency performance was controlled, demonstrating the specificity of their phonological fluency deficit. This study adds to the theoretical debate on the locus of the phonological deficit in dyslexia and DLD. The findings support the hypothesis that the phonological deficit in dyslexia and DLD lies in deficient explicit access to intact phonological representations.
Fully Biodegradable Composites: Thermal, Flammability, Moisture Absorption and Mechanical Properties of Natural Fibre-Reinforced Composites with Nano-Hydroxyapatite

Natural fibre-reinforced poly(lactic acid) (PLA) laminates were prepared by a conventional film stacking method from PLA films and natural fabrics with a cross ply layup of [0/90/0/90/0/90], followed by hot compression. Natural fibre (NF) nano-hydroxyapatite (nHA) filled composites were produced by the same manufacturing technique with matrix films that had varying concentrations of nHA in the PLA. Their flammability, thermal, moisture absorption and mechanical properties were analysed in terms of the amount of nHA. The flame behavior of neat PLA and composites evaluated by the UL-94 test demonstrated that only the composite containing the highest quantity of nHA (i.e., 40 wt% nHA in matrix) was found to achieve an FH-1 rating and exhibited no recorded burn rate, whereas other composites obtained only an FH-3. The thermal degradation temperature and mass residue were also observed, via thermogravimetric analysis, to increase when increasing concentrations of nHA were added to the NF composite. The tensile strength, tensile modulus and flexural modulus of the neat resin were found to increase significantly with the introduction of flax fibre. Conversely, moisture absorption was found to increase and mechanical properties to decrease with both the presence of NF and increasing concentrations of nHA, and subsequent mechanical properties experienced an obvious reduction.
Effects of economic crisis on air quality in Ioannina, Greece

Abstract The aim of this study was to investigate the regime of air pollution in Ioannina, NW Greece during the years of Greek financial crisis. Annual, weekly and daily patterns for PM10, PM2.5, NO2, O3 and Benzene were defined in order to reveal the sources of air pollutants in Ioannina and the time periods of probable episodes. The quality of air was characterized according to the European Environment Agency’s European Air Quality Index, separately for winter and summer, while it was examined if and in what extend the thresholds of European Directives for each pollutant have been exceeded. The air quality in Ioannina was found to be “Good” as far as NO2 and O3 were concerned. In contrast, there were many cases with “Poor” and “Very Poor” conditions related to PM10 and PM2.5 levels, mainly during winter and autumn, caused by wood burning for residential heating. The mean annual concentrations of all pollutants did not exceed EU’s standards, but from 2011 onwards, the number of cases with PM10 mean daily concentration above threshold surpassed the number of permitted exceedences of EU directives.
Social Support Network Types and Depressive Symptoms Among Community-Dwelling Older Adults in South Korea

The purposes of this study were to derive empirical types of social support networks in a sample of 1000 community-dwelling, older Koreans 65 years of age or older and examine which types of social support network are associated with a lower risk of depressive symptoms. Depressive symptom was assessed using the Korean version of the Geriatric Depression Scale–Short Form. Using K-means cluster analysis, we identified 4 social support network types: friend, family, restricted, and diverse. Multivariate linear regression analysis revealed that diverse and family support networks were protective against depressive symptoms, whereas restricted support networks were least. Encouraging older people to develop a variety of social support networks with family and friends may help prevent depressive symptoms in the community-dwelling elderly. These findings extended prior studies and provided valuable information on how to prevent depressive symptoms of the community-dwelling elderly.
Codon Usage Bias Analysis of Citrus tristeza virus: Higher Codon Adaptation to Citrus reticulata Host

Citrus tristeza virus (CTV), a member of the aphid-transmitted closterovirus group, is the causal agent of the notorious tristeza disease in several citrus species worldwide. The codon usage patterns of viruses reflect the evolutionary changes for optimization of their survival and adaptation in their fitness to the external environment and the hosts. The codon usage adaptation of CTV to specific citrus hosts remains to be studied; thus, its role in CTV evolution is not clearly comprehended. Therefore, to better explain the host–virus interaction and evolutionary history of CTV, the codon usage patterns of the coat protein (CP) genes of 122 CTV isolates originating from three economically important citrus hosts (55 isolate from Citrus sinensis, 38 from C. reticulata, and 29 from C. aurantifolia) were studied using several codon usage indices and multivariate statistical methods. The present study shows that CTV displays low codon usage bias (CUB) and higher genomic stability. Neutrality plot and relative synonymous codon usage analyses revealed that the overall influence of natural selection was more profound than that of mutation pressure in shaping the CUB of CTV. The contribution of high-frequency codon analysis and codon adaptation index value show that CTV has host-specific codon usage patterns, resulting in higheradaptability of CTV isolates originating from C. reticulata (Cr-CTV), and low adaptability in the isolates originating from C. aurantifolia (Ca-CTV) and C. sinensis (Cs-CTV). The combination of codon analysis of CTV with citrus genealogy suggests that CTV evolved in C. reticulata or other Citrus progenitors. The outcome of the study enhances the understanding of the factors involved in viral adaptation, evolution, and fitness toward their hosts. This information will definitely help devise better management strategies of CTV.
Large Cell Neuroendocrine Carcinoma of the Prostate: A Systematic Review and Pooled Analysis

Background: Large cell neuroendocrine carcinoma (LCNEC) of the prostate is an extremely rare entity, and the clinicopathological course, potential effective treatment, and prognosis are yet to be elucidated. Materials and Methods: A systematic search in Pubmed, Embase, and Ovid from inception to January 2019 was conducted. We reviewed each individual case of prostatic LCNEC and summarized specific features and outcomes for this rare pathologic entity. Results: Thirteen studies with a total of 20 patients (mean age: 70.3, range 43–87) were included in our review. Seventeen patients harbored primary LCNEC of the prostate, of which 9 patients were diagnosed with de novo carcinoma, and 8 patients were with a history of prostatic adenocarcinoma treated with hormonal therapy (mean duration: 2.9 years, range 2–5). The other 3 patients were diagnosed with metastatic LCNEC originating from lung (2 cases) and bladder (1 case). All patients met the diagnostic criteria of the typical morphological features as well as immunohistochemical staining results. Nearly all primary de novo LCNEC of the prostate were at a late stage at initial diagnosis. The pattern of distant metastasis resembled that of prostatic adenocarcinoma with the most common sites as bone spread (8/16, 50%). Most patients received systematic chemotherapy after diagnosis; however, the prognosis remained poor and patients deteriorated rapidly but with exception. Three reported cases in the context of de novo LCNEC admixed with prostatic adenocarcinoma kept sustained response to androgen deprivation therapy (ADT) and achieved obviously better survival outcomes compared with other patients. Conclusions: LCNEC of the prostate is a rare entity that mostly occurs after long-standing hormonal therapy of prostatic adenocarcinoma. The prognosis was universally poor irrespective of the systematic chemotherapy. However, patients of de novo tumor mixed with prostatic adenocarcinoma may respond to ADT and harbor a better outcome than those of pure de novo or post-ADT LCNEC of the prostate.
Effects of Normothermic Machine Perfusion Conditions on Mesenchymal Stromal Cells

Ex-situ normothermic machine perfusion (NMP) of transplant kidneys allows assessment of kidney quality and targeted intervention to initiate repair processes prior to transplantation. Mesenchymal stromal cells (MSC) have been shown to possess the capacity to stimulate kidney repair. Therefore, the combination of NMP and MSC therapy offers potential to repair transplant kidneys. It is however unknown how NMP conditions affect MSC. In this study the effect of NMP perfusion fluid on survival, metabolism and function of thawed cryopreserved human (h)MSC and porcine (p)MSC in suspension conditions was studied. Suspension conditions reduced the viability of pMSC by 40% in both perfusion fluid and culture medium. Viability of hMSC was reduced by suspension conditions by 15% in perfusion fluid, whilst no differences were found in survival in culture medium. Under adherent conditions, survival of the cells was not affected by perfusion fluid. The perfusion fluid did not affect survival of fresh MSC in suspension compared to the control culture medium. The freeze-thawing process impaired the survival of hMSC; 95% survival of fresh hMSC compared to 70% survival of thawed hMSC. Moreover, thawed MSC showed increased levels of reactive oxygen species, which indicates elevated levels of oxidative stress, and reduced mitochondrial activity, which implies reduced metabolism. The adherence of pMSC and hMSC to endothelial cells was reduced after the thawing process, effect which was particularly profound in in the perfusion fluid. To summarize, we observed that conditions required for machine perfusion are influencing the behavior of MSC. The freeze-thawing process reduces survival and metabolism and increases oxidative stress, and diminishes their ability to adhere to endothelial cells. In addition, we found that hMSC and pMSC behaved differently, which has to be taken into consideration when translating results from animal experiments to clinical studies.
Non-verbal speech cues as objective measures for negative symptoms in patients with schizophrenia

Negative symptoms in schizophrenia are associated with significant burden and possess little to no robust treatments in clinical practice today. One key obstacle impeding the development of better treatment methods is the lack of an objective measure. Since negative symptoms almost always adversely affect speech production in patients, speech dysfunction have been considered as a viable objective measure. However, researchers have mostly focused on the verbal aspects of speech, with scant attention to the non-verbal cues in speech. In this paper, we have explored non-verbal speech cues as objective measures of negative symptoms of schizophrenia. We collected an interview corpus of 54 subjects with schizophrenia and 26 healthy controls. In order to validate the non-verbal speech cues, we computed the correlation between these cues and the NSA-16 ratings assigned by expert clinicians. Significant correlations were obtained between these non-verbal speech cues and certain NSA indicators. For instance, the correlation between Turn Duration and Restricted Speech is -0.5, Response time and NSA Communication is 0.4, therefore indicating that poor communication is reflected in the objective measures, thus validating our claims. Moreover, certain NSA indices can be classified into observable and non-observable classes from the non-verbal speech cues by means of supervised classification methods. In particular the accuracy for Restricted speech quantity and Prolonged response time are 80% and 70% respectively. We were also able to classify healthy and patients using non-verbal speech features with 81.3% accuracy.
Neutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of Plasmodium falciparum into human erythrocytes

An effective vaccine is a priority for malaria control and elimination. The leading candidate in the Plasmodium falciparum blood stage is PfRh5. PfRh5 assembles into trimeric complex with PfRipr and PfCyRPA in the parasite, and this complex is essential for erythrocyte invasion. In this study, we show that antibodies specific for PfRh5 and PfCyRPA prevent trimeric complex formation. We identify the EGF‐7 domain on PfRipr as a neutralising epitope and demonstrate that antibodies against this region act downstream of complex formation to prevent merozoite invasion. Antibodies against the C‐terminal region of PfRipr were more inhibitory than those against either PfRh5 or PfCyRPA alone, and a combination of antibodies against PfCyRPA and PfRipr acted synergistically to reduce invasion. This study supports prioritisation of PfRipr for development as part of a next‐generation antimalarial vaccine.
Perceived distress, personality characteristics, coping strategies and psychosocial impairments in a national German multicenter cohort of patients with Crohn’s disease and ulcerative colitis

Abstract Background and aims This study examined differences in personality, psychological distress, and stress coping in inflammatory bowel disease (IBD) depending on type of disease and disease activity. We compared patients suffering from Crohn’s disease (CD) and ulcerative colitis (UC) with controls. While the literature is replete with distinctive features of the pathogenesis of IBD, the specific differences in psychological impairments are not well studied. Methods In this German national multicenter study, participants were recruited from 32 centers. Two hundred ninety-seven questionnaires were included, delivering vast information on disease status and psychological well-being based on validated instruments with a total of 285 variables. Results CD patients were more affected by psychological impairments than patients suffering from UC or controls. Importantly, patients with active CD scored higher in neuroticism (p < 0.01), psychological distress (p < 0.001) and maladaptive stress coping (escape, p = 0.03; rumination, p < 0.03), but less need for social support (p = 0.001) than controls. In contrast, patients suffering from active UC showed psychological distress (p < 0.04) and maladaptive coping (avoidance, p < 0.03; escape, p = 0.01). Patients in remission seemed to be less affected. In particular, patients with UC in remission were not inflicted by psychological impairments. The group of CD patients in remission however, showed insecurity (p < 0.01) and paranoid ideation (p = 0.04). Conclusions We identified specific aspects of psychological impairment in IBD depending on disease and disease activity. Our results underscore the need for psychological support and treatment particularly in active CD.
On the influence of the shoulder kinematic chain on joint kinematics and musculotendon lengths during wheelchair propulsion estimated from multibody kinematics optimization.

Multibody kinematic optimization is frequently used to assess shoulder kinematics during manual wheelchair (MWC) propulsion but multiple kinematics chains are available. It is hypothesized that these different kinematic chains affect marker tracking, shoulder kinematics and resulting musculotendon (MT) lengths. In this study, shoulder kinematics and MT lengths obtained from four shoulder kinematic chains (open-loop thorax-clavicle-scapula-humerus (M1), closed-loop with contact ellipsoid (M2), scapula rhythm from regression equations (M3), and a single ball-and- socket joint between the thorax and the humerus (M4) were compared. Right-side shoulder kinematics from seven subjects were obtained with 34 reflective markers and a scapula locator using an optoelectronic motion capture system while propelling on a MWC simulator. Data was processed based on the four models. Results showed the impact of shoulder kinematic chains on all studied variables. Marker reconstruction errors were found similar between M1 and M2 and lower than for M3 and M4. Few degrees of freedom (DoF) were noticeably different between M1 and M2, but all shoulder DoFs were significantly affected between M1 and M4. As a consequence of differences in joint kinematics, MT lengths were affected by the kinematic chain definition. The contact ellipsoid (M2) was found as a good trade-off between marker tracking and penetration avoidance of the scapula. The regression-based model (M3) was less efficient due to limited humerus elevation during MWC propulsion, as well as the ball-and-socket model (M4) which appeared not suitable for upper limbs activities, including MWC propulsion.