Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimating the impact of divergent mating phenology between residents and migrants on the potential for gene flow

Abstract Gene flow between populations can allow the spread of beneficial alleles and genetic diversity between populations, with importance to conservation, invasion biology, and agriculture. Levels of gene flow between populations vary not only with distance, but also with divergence in reproductive phenology. Since phenology is often locally adapted, arriving migrants may be reproductively out of synch with residents, which can depress realized gene flow. In flowering plants, the potential impact of phenological divergence on hybridization between populations can be predicted from overlap in flowering schedules—the daily count of flowers capable of pollen exchange—between a resident and migrant population. The accuracy of this prospective hybridization estimate, based on parental phenotypes, rests upon the assumptions of unbiased pollen transfer between resident and migrant active flowers. We tested the impact of phenological divergence on resident–migrant mating frequencies in experiments that mimicked a single large gene flow event. We first prospectively estimated mating frequencies two lines of Brassica rapaselected or early and late flowering. We then estimated realized mating frequencies retrospectively through progeny testing. The two estimates strongly agreed in a greenhouse experiment, where procedures ensured saturating, unbiased pollination. Under natural pollination in the field, the rate of resident–migrant mating, was lower than estimated by phenological divergence alone, although prospective and retrospective estimates were correlated. In both experiments, differences between residents and migrants in flowering schedule shape led to asymmetric hybridization. Results suggest that a prospective estimate of hybridization based on mating schedules can be a useful, although imperfect, tool for evaluating potential gene flow. They also illustrate the impact of mating phenology on the magnitude and symmetry of reproductive isolation.
Vaccine Prices: A Systematic Review of Literature

Vaccines are among the most vital interventions to control and reduce the morbidity and mortality worldwide. In accessing vaccines, pricing is usually the single most important deciding element. However, there is a scarcity of the literature on the vaccines pricing. The current study aims to review vaccine prices from the published literature and to evaluate factors that impact the pricing of vaccines. The literature (from 2015–2020) was reviewed to identify the original research articles. Systematic searches were conducted across the five databases including, Google Scholar, PubMed, Science Direct, Scopus and Springer Link. Literature search yielded 23,626 articles, of which 7351 were screened and 7310 articles were excluded based on title and abstracts relevance. The 41 studies were selected for full text review and 4 studies were found to meet the inclusion criteria. The included studies discussed vaccine prices for childhood vaccines, for Human Papilloma Virus (HPV) in US, China and in Europe. One study detailed the various scenarios of the HPV vaccines pricing. It was found that recently introduced vaccines have higher prices owing to the involvement of technology and research for their manufacture. However, prices tended to decrease over some maturation in price and by the involvement of Global Alliance for Vaccine Initiative (GAVI) and other allies. The prices of vaccines in China were much lower than the other high-income countries and the prices offered through United Nations Children’s Fund (UNICEF), mainly due to the large scale of demand in China. The affordable prices of vaccines were related to delicate procedures involving multiple stakeholders and a shorter duration of contract. This review systematically evaluated the literature and identified key factors that could impact vaccines pricing. The prices were higher for the newly introduced vaccines into the market. However, with the price maturation, there was a decline in the pricing and affordable prices could be achieved through tender pricing and involvement of GAVI and other allies.
Reading skills deficits in people with mental illness: A systematic review and meta-analysis

Abstract Background Good reading skills are important for appropriate functioning in everyday life, scholastic performance, and acquiring a higher socioeconomic status. We conducted the first systematic review and meta-analysis to quantify possible deficits in specific reading skills in people with a variety of mental illnesses, including personality disorders (PDs). Methods We performed a systematic search of multiple databases from inception until February 2020 and conducted random-effects meta-analyses. Results The search yielded 34 studies with standardized assessments of reading skills in people with one or more mental illnesses. Of these, 19 studies provided data for the meta-analysis. Most studies (k = 27; meta-analysis, k = 17) were in people with schizophrenia and revealed large deficits in phonological processing (Hedge’s g = −0.88, p < 0.00001), comprehension (Hedge’s g = −0.96, p < 0.00001) and reading rate (Hedge’s g = −1.22, p = 0.002), relative to healthy controls; the single-word reading was less affected (Hedge’s g = −0.70, p < 0.00001). A few studies in affective disorders and nonforensic PDs suggested weaker deficits (for all, Hedge’s g < −0.60). In forensic populations with PDs, there was evidence of marked phonological processing (Hedge’s g = −0.85, p < 0.0001) and comprehension deficits (Hedge’s g = −0.95, p = 0.0003). Conclusions People with schizophrenia, and possibly forensic PD populations, demonstrate a range of reading skills deficits. Future studies are needed to establish how these deficits directly compare to those seen in developmental or acquired dyslexia and to explore the potential of dyslexia interventions to improve reading skills in these populations.
Emotional state, fatigue, functional status and quality of life in breast cancer: exploring the moderating role of psychological inflexibility

ABSTRACT Previous findings demonstrate that psychological flexibility (PF) might be a protective factor regarding distress in breast cancer patients. Our research aimed to examine the moderating effect of psychological inflexibility (PI) on the relationship between emotional state, fatigue, functional status and quality of life (QOL) in breast cancer. The research was conducted on 64 women (Mage=58.36, SD=11.30) while undergoing radiation therapy. Five moderation analyses were performed with depression, anxiety, stress (Depression Anxiety Stress Scales – 21; DASS-21), fatigue (the Fatigue Assessment Scale Serbian; FAS) and functional status (the Upper Extremity Functional Index; UEFI) as predictors, QOL (Quality of Life Instrument – Breast Cancer Patient Version; QOL-BC) as criterion and PI (Acceptance and Action Questionnaire; AAQ II) as a moderator. The significant moderating effect of PI was obtained in the relationship of QOL with the depression, anxiety, fatigue and functional status. As anxiety, depression, fatigue and functional difficulties decrease, participants who are psychologically flexible report better QOL. On the other hand, psychologically inflexible individuals consistently report impaired QOL, regardless of whether indicators of depression, anxiety, fatigue and diminished functional status are prominent or not. Our findings support the notion that PF may have an important role in the improvement of emotional state and QOL in breast cancer patients. It would be also plausible to assume that interventions aimed at modifying the capacity for PF, might be useful in coping with fatigue and functional complications, which should be explored in future studies.
A proteomic survey of microtubule-associated proteins in a R402H TUBA1A mutant mouse

Microtubules play a critical role in multiple aspects of neurodevelopment, including the generation, migration and differentiation of neurons. A recurrent mutation (R402H) in the α-tubulin gene TUBA1A is known to cause lissencephaly with cerebellar and striatal phenotypes. Previous work has shown that this mutation does not perturb the chaperone-mediated folding of tubulin heterodimers, which are able to assemble and incorporate into the microtubule lattice. To explore the molecular mechanisms that cause the disease state we generated a new conditional mouse line that recapitulates the R402H variant. We show that heterozygous mutants present with laminar phenotypes in the cortex and hippocampus, as well as a reduction in striatal size and cerebellar abnormalities. We demonstrate that homozygous expression of the R402H allele causes neuronal death and exacerbates a cell intrinsic defect in cortical neuronal migration. Microtubule sedimentation assays coupled with quantitative mass spectrometry demonstrated that the binding and/or levels of multiple microtubule associated proteins (MAPs) are perturbed by the R402H mutation including VAPB, REEP1, EZRIN, PRNP and DYNC1l1/2. Consistent with these data we show that the R402H mutation impairs dynein-mediated transport which is associated with a decoupling of the nucleus to the microtubule organising center. Our data support a model whereby the R402H variant is able to fold and incorporate into microtubules, but acts as a gain of function by perturbing the binding of MAPs.
Heart rate variability during cardiovascular reflex testing: the importance of underlying heart rate

Abstract Objectives Heart rate variability (HRV) is often measured during clinical and experimental cardiovascular reflex tests (CRT), as a reflection of cardiac autonomic modulation, despite limited characterization of the rapid responses that occur. Therefore, we evaluated the responsiveness of HRV indices in 20 healthy young adults (age, 27 ± 6 y; mass, 76.9 ± 16.8 kg; height, 1.79 ± 0.12 m) during four separate established CRT. Methods These included the [I] orthostatic challenge, [II] isometric handgrip, [III] cold pressor and [IV] cold diving reflex tests. Electrocardiogram was recorded throughout, with HRV derived from RR intervals at rest and from each CRT. On a separate day, a subgroup of participants (n=9) completed the same protocol for a second time. Results The maximal slope of heart rate change (dTdt) was significantly different between all CRT, with the orthostatic challenge producing the fastest increase (2.56 ± 0.48) and the cold pressor the fastest reduction (−1.93 ± 0.68) in heart rate. Overall HRV, reflected by Poincaré plot ratio (SD1:SD2), was significantly reduced during all CRT ([I], −0.41 ± 0.12; [II], −0.19 ± 0.05; [III], −0.36 ± 0.12; [IV], −0.44 ± 0.11; p<0.05) relative to baseline and this was reproducible in time-series. However, when HRV indices were correlated to mean-RR an exponential growth-like relationship was evident (R2 ranging from: 0.52–0.62). Conclusions These unique outcomes demonstrate that short-term alterations in HRV are evident during CRT, while indicating the importance of adjusting for, or at least reporting, underlying heart rate when interpreting such measures.
Photodynamic Therapy with Verteporfin for Chronic Central Serous Chorioretinopathy: A Review of Data and Efficacy

Central serous chorioretinopathy represents the fourth most frequent retinal disorder, occurring especially in young age. Central serous chorioretinopathy is mainly characterized by macular serous retinal detachment and although the clinical course moves frequently toward a spontaneous resolution, the subretinal fluid may persist for a long time, thus evolving to the chronic form, and leading to a potential damage of the retinal pigment epithelium and to photoreceptors. The photodynamic therapy with verteporfin plays an important role in the armamentarium among the many therapeutic options employed in this complex retinal disorder. In this review, the authors aim to summarize data of efficacy and safety of PDT focusing especially on mechanisms of action of the PDT and providing comparative outcomes with the alternative therapeutic approaches, including especially the subthreshold laser treatment.
Echolocating bats accumulate information from acoustic snapshots to predict auditory object motion

Significance Research on visual tracking of moving stimuli has contributed to our understanding of sensory-guided behaviors; however, the processes that support auditory object tracking in natural three-dimensional environments remain largely unknown. This is important, not only to diverse groups of animals, but also to humans that rely on hearing to track objects in their environment. For visually impaired individuals, hearing is paramount for auditory object tracking and navigation, and in recent years, mobility training programs for the blind include instruction on echolocation using tongue clicks. In this work, we provide conclusive demonstration that echolocating bats use predictive strategies to track moving auditory objects, which can inform future comparative work on auditory motion processing. Unlike other predators that use vision as their primary sensory system, bats compute the three-dimensional (3D) position of flying insects from discrete echo snapshots, which raises questions about the strategies they employ to track and intercept erratically moving prey from interrupted sensory information. Here, we devised an ethologically inspired behavioral paradigm to directly test the hypothesis that echolocating bats build internal prediction models from dynamic acoustic stimuli to anticipate the future location of moving auditory targets. We quantified the direction of the bat’s head/sonar beam aim and echolocation call rate as it tracked a target that moved across its sonar field and applied mathematical models to differentiate between nonpredictive and predictive tracking behaviors. We discovered that big brown bats accumulate information across echo sequences to anticipate an auditory target’s future position. Further, when a moving target is hidden from view by an occluder during a portion of its trajectory, the bat continues to track its position using an internal model of the target’s motion path. Our findings also reveal that the bat increases sonar call rate when its prediction of target trajectory is violated by a sudden change in target velocity. This shows that the bat rapidly adapts its sonar behavior to update internal models of auditory target trajectories, which would enable tracking of evasive prey. Collectively, these results demonstrate that the echolocating big brown bat integrates acoustic snapshots over time to build prediction models of a moving auditory target’s trajectory and enable prey capture under conditions of uncertainty.
Obesity in Qatar: A Case-Control Study on the Identification of Associated Risk Factors

Obesity is an emerging public health problem in the Western world as well as in the Gulf region. Qatar, a tiny wealthy county, is among the top-ranked obese countries with a high obesity rate among its population. Compared to Qatar’s severity of this health crisis, only a limited number of studies focused on the systematic identification of potential risk factors using multimodal datasets. This study aims to develop machine learning (ML) models to distinguish healthy from obese individuals and reveal potential risk factors associated with obesity in Qatar. We designed a case-control study focused on 500 Qatari subjects, comprising 250 obese and 250 healthy individuals- the later forming the control group. We obtained the most extensive collection of clinical measurements for the Qatari population from the Qatar Biobank (QBB) repertoire, including (i) Physio-clinical Biomarkers, (ii) Spirometry, (iii) VICORDER, (iv) DXA scan composition, and (v) DXA scan densitometry readings. We developed several machine learning (ML) models to distinguish healthy from obese individuals and applied multiple feature selection techniques to identify potential risk factors associated with obesity. The proposed ML model achieved over 90% accuracy, thereby outperforming the existing state of the art models. The outcome from the ablation study on multimodal clinical datasets revealed physio-clinical measurements as the most influential risk factors in distinguishing healthy versus obese subjects. Furthermore, multiple feature ranking techniques confirmed known obesity risk factors (c-peptide, insulin, albumin, uric acid) and identified potential risk factors linked to obesity-related comorbidities such as diabetes (e.g., HbA1c, glucose), liver function (e.g., alkaline phosphatase, gamma-glutamyl transferase), lipid profile (e.g., triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol), etc. Most of the DXA measurements (e.g., bone area, bone mineral composition, bone mineral density, etc.) were significantly (p-value < 0.05) higher in the obese group. Overall, the net effect of hypothesized protective factors of obesity on bone mass seems to have surpassed the hypothesized harmful factors. All the identified factors warrant further investigation in a clinical setup to understand their role in obesity.
CDKN1B mutation and copy number variation are associated with tumor aggressiveness in luminal breast cancer

The CDKN1B gene, encoding for the CDK inhibitor p27kip1, is mutated in defined human cancer subtypes, including breast, prostate carcinomas and small intestine neuroendocrine tumors. Lessons learned from small intestine neuroendocrine tumors suggest that CDKN1B mutations could be subclonal, raising the question of whether a deeper sequencing approach could lead to the identification of higher numbers of patients with mutations. Here, we addressed this question and analyzed human cancer biopsies from breast (n = 396), ovarian (n = 110) and head and neck squamous carcinoma (n = 202) patients, using an ultra‐deep sequencing approach. Notwithstanding this effort, the mutation rate of CDKN1B remained substantially aligned with values from the literature, showing that essentially only hormone receptor‐positive breast cancer displayed CDKN1B mutations in a relevant number of cases (3%). However, the analysis of copy number variation showed that another fraction of luminal breast cancer displayed loss (8%) or gain (6%) of the CDKN1B gene, further reinforcing the idea that the function of p27kip1 is important in this type of tumor. Intriguingly, an enrichment for CDKN1B alterations was found in samples from premenopausal luminal breast cancer patients (n = 227, 4%) and in circulating cell‐free DNA from metastatic luminal breast cancer patients (n = 59, 8.5%), suggesting that CDKN1B alterations could correlate with tumor aggressiveness and/or occur later during disease progression. Notably, many of the identified somatic mutations resulted in p27kip1 protein truncation, leading to loss of most of the protein or of its C‐terminal domain. Using a gene‐editing approach in a luminal breast cancer cell line, MCF‐7, we observed that the expression of p27kip1 truncating mutants that lose the C‐terminal domains failed to rescue most of the phenotypes induced by CDKN1B gene knockout, indicating that the functions retained by the C‐terminal portion are critical for its role as an oncosuppressor, at least in luminal breast cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Autophagy and Lc3-Associated Phagocytosis in Zebrafish Models of Bacterial Infections

Modeling human infectious diseases using the early life stages of zebrafish provides unprecedented opportunities for visualizing and studying the interaction between pathogens and phagocytic cells of the innate immune system. Intracellular pathogens use phagocytes or other host cells, like gut epithelial cells, as a replication niche. The intracellular growth of these pathogens can be counteracted by host defense mechanisms that rely on the autophagy machinery. In recent years, zebrafish embryo infection models have provided in vivo evidence for the significance of the autophagic defenses and these models are now being used to explore autophagy as a therapeutic target. In line with studies in mammalian models, research in zebrafish has shown that selective autophagy mediated by ubiquitin receptors, such as p62, is important for host resistance against several bacterial pathogens, including Shigella flexneri, Mycobacterium marinum, and Staphylococcus aureus. Furthermore, an autophagy related process, Lc3-associated phagocytosis (LAP), proved host beneficial in the case of Salmonella Typhimurium infection but host detrimental in the case of S. aureus infection, where LAP delivers the pathogen to a replication niche. These studies provide valuable information for developing novel therapeutic strategies aimed at directing the autophagy machinery towards bacterial degradation.
Micaryolanes A and B, Two New Caryolane‐Type Sesquiterpenoids from Marine Streptomyces sp. AH25

Caryolanes, known as β‐caryophyllene alcohols, are widely occurring sesquiterpenes in plants. From the cultures of marine Streptomyces sp. AH25, two new caryolane sesquiterpenes, micaryolanes A and B (1 and 2), together with caryolan‐1,9β‐diol (3) were isolated. Their structures were elucidated by extensive analyses of HR‐MS and NMR spectroscopic data. The absolute configurations were assigned via the CD data of the in situ formed [Rh2(OCOCF3)4] complex and supported by comparison of experimental and calculated specific rotation values. Compounds 1–3 exhibited no activities against Hep3B or MG‐63 cell lines or against Gram‐positive and Gram‐negative bacteria. The results not only enriched the caryolane family, but also proved bacteria as a productive source of terpene metabolites.
Spatial and temporal dynamics of European hake (Merluccius merluccius) in the North Sea

Catches of European hake (Merluccius merluccius) in the North Sea have increased substantially during the last decade, even though there is no directed commercial fishery of hake in this area. We analysed the spatial distributions of hake in the northern the parts of its range, (where it is less well-studied), using ICES international bottom trawl survey data from 1997 to 2015. We examine length-frequency distributions for (i) distinct modes enabling the assignment of fish into categories which likely corresponded to the ages 1, 2, and 3+ and (ii) patterns of seasonal spatial distribution for the different groups. Age categories 1 and 2 fish were most abundant in the northern North Sea, and appear to remain in the North Sea until 2 years of age, when they move into deeper waters. Their distribution has expanded into the western-central North Sea in the last decade. Age category 3+ fish were most abundant in the northern and central North Sea during summer, indicating a seasonal influx of large individuals into this area likely associated with spawning activity. The distribution of these older fish has gradually expanded westward in both seasons.