Miracle-dz/UniFAR-FTUs huggingface dataset:
Random Network Models to Predict the Long-Term Impact of HPV Vaccination on Genital Warts

The Human papillomaviruses (HPV) vaccine induces a herd immunity effect in genital warts when a large number of the population is vaccinated. This aspect should be taken into account when devising new vaccine strategies, like vaccination at older ages or male vaccination. Therefore, it is important to develop mathematical models with good predictive capacities. We devised a sexual contact network that was calibrated to simulate the Spanish epidemiology of different HPV genotypes. Through this model, we simulated the scenario that occurred in Australia in 2007, where 12–13 year-old girls were vaccinated with a three-dose schedule of a vaccine containing genotypes 6 and 11, which protect against genital warts, and also a catch-up program in women up to 26 years of age. Vaccine coverage were 73% in girls with three doses and with coverage rates decreasing with age until 52% for 20–26 year-olds. A fast 59% reduction in the genital warts diagnoses occurred in the model in the first years after the start of the program, similar to what was described in the literature.
DNA methylation and breast tumor clinicopathological features: The Western New York Exposures and Breast Cancer (WEB) study

ABSTRACT We evaluated the association between methylation of 9 genes, SCGB3A1, GSTP1, RARB, SYK, FHIT, CDKN2A, CCND2, BRCA1, and SFN in tumor samples from 720 breast cancer cases with clinicopathological features of the tumors and survival. Logistic regression was used to estimate odds ratios (OR) of methylation and Cox proportional hazards models to estimate hazard ratios (HR) between methylation and breast cancer related mortality. Estrogen receptor (ER) and progesterone receptor (PR) positivity were associated with increased SCGB3A1 methylation among pre- and post-menopausal cases. Among premenopausal women, compared with Stage 0 cases, cases of invasive cancer were more likely to have increased methylation of RARB (Stage I OR = 4.7, 95% CI: 1.1–19.0; Stage IIA/IIB OR = 9.7, 95% CI: 2.4–39.9; Stage III/IV OR = 5.6, 95% CI: 1.1–29.4) and lower methylation of FHIT (Stage I OR = 0.2, 95% CI: 0.1–0.9; Stage IIA/IIB OR = 0.2, 95% CI: 0.1–0.8; Stage III/IV OR = 0.6, 95% CI: 0.1–3.4). Among postmenopausal women, methylation of SYK was associated with increased tumor size (OR = 1.7, 95% CI: 1.0–2.7) and higher nuclear grade (OR = 2.0, 95% CI 1.2–3.6). Associations between methylation and breast cancer related mortality were observed among pre- but not post-menopausal women. Methylation of SCGB3A1 was associated with reduced risk of death from breast cancer (HR = 0.41, 95% CI: 0.17–0.99) as was BRCA1 (HR = 0.41, 95% CI: 0.16–0.97). CCND2 methylation was associated with increased risk of breast cancer mortality (HR = 3.4, 95% CI: 1.1–10.5). We observed differences in methylation associated with tumor characteristics; methylation of these genes was also associated with breast cancer survival among premenopausal cases. Understanding of the associations of DNA methylation with other clinicopathological features may have implications for prevention and treatment.
GENETIC VARIABILITY FOR YIELD PARAMETERS IN MAIZE (Zea Mays L.) GENOTYPES

The present study was conducted to assess the magnitude of genetic variability in maize genotypes for yield and yield components under agro climatic conditions of Peshawar valley. The experiment was conducted at NWFP Agricultural University Peshawar, during spring 2005. Significant variability was observed for cob length, grains rows cob 1 , fresh cob weight, grain moisture content, 300-grains weight and grain yield. Sarhad white had maximum cob length (16cm) while PESV-3-1 and EV-2 x Pahari had least cob length (11cm). Azam and EV-2 x Pehari had maximum number of grain rows cob -1 (16cm), while minimum grain rows cob -1 was recorded in Jalal and FRW-4 x EV-3 (13cm). Data recorded for fresh cob weight showed that genotype FRW-4 X EV-3 (Late) had maximum fresh cob weight (14.30kg) while the minimum fresh cob weight (4.4kg) was recorded for EV-2. The maximum percent grain moisture content was obtained in genotype PESV-3-3 ( 43.40%), while the minimum was obtained in the genotype EV-2 (15.00%), maximum value for 300 grain weight was shown by Azam (11.0g), while the minimum value (6.2g) was recorded in genotype FRW4 x EV-3 (Late). FRW-4 x EV-3 (Late) showed higher grain yield ha -1 with the value of 11900 kg ha -1 , while the genotype Azam had low grain yield ha -1 (1171 kg ha -1 ). The present study revealed considerable amount of diversity among the
The morphometric co‐atrophy networking of schizophrenia, autistic and obsessive spectrum disorders

By means of a novel methodology that can statistically derive patterns of co‐alterations distribution from voxel‐based morphological data, this study analyzes the patterns of brain alterations of three important psychiatric spectra—that is, schizophrenia spectrum disorder (SCZD), autistic spectrum disorder (ASD), and obsessive‐compulsive spectrum disorder (OCSD). Our analysis provides five important results. First, in SCZD, ASD, and OCSD brain alterations do not distribute randomly but, rather, follow network‐like patterns of co‐alteration. Second, the clusters of co‐altered areas form a net of alterations that can be defined as morphometric co‐alteration network or co‐atrophy network (in the case of gray matter decreases). Third, within this network certain cerebral areas can be identified as pathoconnectivity hubs, the alteration of which is supposed to enhance the development of neuronal abnormalities. Fourth, within the morphometric co‐atrophy network of SCZD, ASD, and OCSD, a subnetwork composed of eleven highly connected nodes can be distinguished. This subnetwork encompasses the anterior insulae, inferior frontal areas, left superior temporal areas, left parahippocampal regions, left thalamus and right precentral gyri. Fifth, the co‐altered areas also exhibit a normal structural covariance pattern which overlaps, for some of these areas (like the insulae), the co‐alteration pattern. These findings reveal that, similarly to neurodegenerative diseases, psychiatric disorders are characterized by anatomical alterations that distribute according to connectivity constraints so as to form identifiable morphometric co‐atrophy patterns.
GPCRs Direct Germline Development and Somatic Gonad Function in Planarians

Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues in response to systemic and environmental cues. Here, we investigated the role of G protein-coupled receptors (GPCRs) in this dynamic germline regulation. By genome-enabled receptor mining, we identified 566 putative planarian GPCRs and classified them into conserved and phylum-specific subfamilies. We performed a functional screen to identify NPYR-1 as the cognate receptor for NPY-8, a neuropeptide required for sexual maturation and germ cell differentiation. Similar to NPY-8, knockdown of this receptor results in loss of differentiated germ cells and sexual maturity. NPYR-1 is expressed in neuroendocrine cells of the central nervous system and can be activated specifically by NPY-8 in cell-based assays. Additionally, we screened the complement of GPCRs with expression enriched in sexually reproducing planarians, and identified an orphan chemoreceptor family member, ophis, that controls differentiation of germline stem cells (GSCs). ophis is expressed in somatic cells of male and female gonads, as well as in accessory reproductive tissues. We have previously shown that somatic gonadal cells are required for male GSC specification and maintenance in planarians. However, ophis is not essential for GSC specification or maintenance and, therefore, defines a secondary role for planarian gonadal niche cells in promoting GSC differentiation. Our studies uncover the complement of planarian GPCRs and reveal previously unappreciated roles for these receptors in systemic and local (i.e., niche) regulation of germ cell development.
The impact of interleukin-10 (IL-10) gene 4 polymorphisms on peripheral blood IL-10 variation and prostate cancer risk based on published studies

This study purported to investigate the impact of interleukin-10 (IL-10) gene 4 polymorphisms (−1082G>A, -819T>C, -592A>C and 210T>C) on peripheral blood IL-10 variation and prostate cancer (PCa) risk, with a special consideration given to various origins of between-study heterogeneity. 2 researchers independently fulfilled literature retrieval, quality assessment and information collection. Sub-grouped analyses per ethnicity, continent, design type, control source, genotyping procedure, genotype validation, age-matched status, study sample size, quality score and controls’ mean age were conducted, respectively. Total 17 unduplicated studies (patients/controls: 7561/8101) were assessable for PCa risk, and 4 unduplicated studies (1189 subjects) for peripheral blood IL-10 variation. Pooling all assessable studies identified a marginally significant association between the -1082A allele and increased PCa risk (odds ratio (OR)=1.10, 95% confidence interval [CI]: 1.00 to 1.21) (Heterogeneity I2=64.3%), and no significance was detected in sub-grouped analyses of this polymorphism. Contrastingly, the -592C allele was significantly associated with reduced PCa risk in both prospective (OR=0.85, 95% CI: 0.77 to 0.95) and population-based (OR=0.92, 95% CI: 0.84 to 1.00) studies (Heterogeneity I2=0.0% and 18.1%). Moreover, carriers of combined -592CA/CC genotypes had a significant higher level of peripheral blood IL-10 than the -592AA genotype carriers (weighted mean difference=0.45 and 0.54 mg/dL, 95% CI: 0.23 to 0.67 and 0.30 to 0.39). The above comparisons possessed a low probability of publication bias. In sum, our findings suggested that IL-10 gene -592A>C polymorphism may represent a promising candidate locus for the occurrence of PCa, and further signified a contributing role of this polymorphism in prostate carcinogenesis.
Role of Host Type IA Phosphoinositide 3-Kinase Pathway Components in Invasin-Mediated Internalization of Yersinia enterocolitica

ABSTRACT Many bacterial pathogens subvert mammalian type IA phosphoinositide 3-kinase (PI3K) in order to induce their internalization into host cells. How PI3K promotes internalization is not well understood. Also unclear is whether type IA PI3K affects different pathogens through similar or distinct mechanisms. Here, we performed an RNA interference (RNAi)-based screen to identify components of the type IA PI3K pathway involved in invasin-mediated entry of Yersinia enterocolitica, an enteropathogen that causes enteritis and lymphadenitis. The 69 genes targeted encode known upstream regulators or downstream effectors of PI3K. A similar RNAi screen was previously performed with the food-borne bacterium Listeria monocytogenes. The results of the screen with Y. enterocolitica indicate that at least nine members of the PI3K pathway are needed for invasin-mediated entry. Several of these proteins, including centaurin-α1, Dock180, focal adhesion kinase (FAK), Grp1, LL5α, LL5β, and PLD2 (phospholipase D2), were recruited to sites of entry. In addition, centaurin-α1, FAK, PLD2, and mTOR were required for remodeling of the actin cytoskeleton during entry. Six of the human proteins affecting invasin-dependent internalization also promote InlB-mediated entry of L. monocytogenes. Our results identify several host proteins that mediate invasin-induced effects on the actin cytoskeleton and indicate that a subset of PI3K pathway components promote internalization of both Y. enterocolitica and L. monocytogenes.
The Expression of Antibiotic Resistance Methyltransferase Correlates with mRNA Stability Independently of Ribosome Stalling

ABSTRACT Members of the Erm methyltransferase family modify 23S rRNA of the bacterial ribosome and render cross-resistance to macrolides and multiple distantly related antibiotics. Previous studies have shown that the expression of erm is activated when a macrolide-bound ribosome stalls the translation of the leader peptide preceding the cotranscribed erm. Ribosome stalling is thought to destabilize the inhibitory stem-loop mRNA structure and exposes the erm Shine-Dalgarno (SD) sequence for translational initiation. Paradoxically, mutations that abolish ribosome stalling are routinely found in hyper-resistant clinical isolates; however, the significance of the stalling-dead leader sequence is largely unknown. Here, we show that nonsense mutations in the Staphylococcus aureus ErmB leader peptide (ErmBL) lead to high basal and induced expression of downstream ErmB in the absence or presence of macrolide concomitantly with elevated ribosome methylation and resistance. The overexpression of ErmB is associated with the reduced turnover of the ermBL-ermB transcript, and the macrolide appears to mitigate mRNA cleavage at a site immediately downstream of the ermBL SD sequence. The stabilizing effect of antibiotics on mRNA is not limited to ermBL-ermB; cationic antibiotics representing a ribosome-stalling inducer and a noninducer increase the half-life of specific transcripts. These data unveil a new layer of ermB regulation and imply that ErmBL translation or ribosome stalling serves as a “tuner” to suppress aberrant production of ErmB because methylated ribosome may impose a fitness cost on the bacterium as a result of misregulated translation.
In Vitro and In Vivo Performance of Tissue-Engineered Tendons for Anterior Cruciate Ligament Reconstruction

Background: Anterior cruciate ligament (ACL) reconstruction is the current standard of care for ACL tears. However, the results are not consistently successful; autografts or allografts have certain disadvantages; and synthetic grafts have had poor clinical results. Purpose: To determine if recellularization of decellularized tendons combined with mechanical stimulation in a bioreactor could replicate the mechanical properties of the native ACL and be successfully used for ACL reconstruction in vivo. Study Design: Controlled laboratory study. Methods: Porcine tibialis tendons were decellularized and then recellularized with human adult bone marrow–derived stem cells. Tendons were cultured in a tissue bioreactor that provided biaxial cyclic loading for up to 7 days. To reproduce mechanical stresses similar to those experienced by the ACL within the knee joint, the tendons were subjected to simultaneous tension and torsion in the bioreactor. Expression of tendon-specific genes and newly synthesized collagen and glycosaminoglycan were used to quantify the efficacy of recellularization and dynamic bioreactor culture. The ultimate tensile load to failure and stiffness of recellularized constructs were measured after dynamic stimulation. Finally, the tissue-engineered tendons were used to reconstruct the ACL in 24 pigs, and ultimate tensile load to failure and stiffness were assessed after 3 months. Results: Dynamic bioreactor culture significantly increased the expression of tendon-specific genes, the quantity of newly synthesized collagen and glycosaminoglycan, and the ultimate tensile load and stiffness of recellularized tendons. After in vivo reconstruction, the ultimate tensile load and stiffness of the tissue-engineered tendons increased significantly up to 3 months after surgery and were within 80% of the ultimate tensile load of the natural ACL. Conclusion: This translational study indicates that recellularization and dynamic mechanical stimuli can significantly enhance matrix synthesis and ultimate tensile load of decellularized porcine tibialis tendons. This approach to tissue engineering can be very useful for ACL reconstruction and may overcome some of the disadvantages of autografts and allografts. Clinical Relevance: Dynamic bioreactor cultivation of tissue-engineered tendons may overcome the limitations of autografts and allografts.
Skin lighteners and hair relaxers as risk factors for breast cancer: results from the Ghana breast health study

Skin lighteners and hair relaxers, both common among women of African descent, have been suggested as possibly affecting breast cancer risk. In Accra and Kumasi, Ghana, we collected detailed information on usage patterns of both exposures among 1131 invasive breast cancer cases and 2106 population controls. Multivariate analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for breast cancer risk factors. Control usage was 25.8% for ever use of skin lighteners and 90.0% for use of hair relaxers for >1 year. The OR for skin lighteners was 1.10 (95% CI 0.93-1.32), with higher risks for former (1.21, 0.98-1.50) than current (0.96, 0.74-1.24) users. No significant dose-response relations were seen by duration, age at first use or frequency of use. In contrast, an OR of 1.58 (95% CI 1.15-2.18) was associated with use of hair relaxers, with higher risks for former (2.22, 1.56-3.16) than current (1.39, 1.00-1.93) users. Although numbers of burns were inconsistently related to risk, associations increased with duration of use, restricted to women who predominately used non-lye products (P for trend < 0.01). This was most pronounced among women with few children and those with smaller tumors, suggesting a possible role for other unmeasured lifestyle factors. This study does not implicate a substantial role for skin lighteners as breast cancer risk factors, but the findings regarding hair relaxers were less reassuring. The effects of skin lighteners and hair relaxers on breast cancer should continue to be monitored, especially given some biologic plausibility for their affecting risk.
Effects of the fluid rheology and surface texture on the footprint of passive droplets.

Bloodstain pattern analysis has been used in criminal investigations for more than 100 years. It provides valuable information about the events that took place prior to the formation of bloodstains at a crime scene. Forensic scientists use empirical laws to make a deduction from bloodstains, but the validity of these conclusions has been challenged in courts due to a lack of understanding of the underlying fluid mechanics. With this motivation, this thesis illustrates how mathematical modeling and numerical simulation can help gain insight into the spreading of blood droplets which eventually leads to the formation of a bloodstain. Understanding the fluid mechanics of droplet spreading and sliding has been accomplished with the help of the lubrication approximation which simplifies the Navier-Stokes equations to a more tractable form, i.e. a coupled set of non-linear partial differential equations. The resulting highly non-linear coupled set of equations is discretized using Finite-Difference. The resulting algebraic system is solved via an efficient Multigrid algorithm. These equations are modified to understand the effects of contact angle hysteresis, fluid rheology and absorptive properties of substrates on sliding dynamics. Variations in the inclination of the substrate cause the droplets to attain different advancing and receding contact angles as they slide down the incline under gravitational pull. This work explores a new way to introduce contact angle hysteresis in the numerical simulation to predict the different phases of a sliding droplet. Experiments of fluid droplet spreading/sliding on inclined surfaces have been performed to measure the terminal sliding velocity. A simplified hysteresis model has been proposed. This model automatically locates the section of the contact line which is advancing and the section which is receding which enables the application of the contact angles for the advancing and receding fronts and therefore takes into account contact angle hysteresis. A simplified analytical model is also suggested for droplets moving down the incline with near circular footprints. With the inclusion of the contact angle hysteresis, simulation results were brought in closer agreement with the experimental ones and the results from both were compared with the results from the analytical model. Blood is a shear-thinning fluid. One of the main objectives of this study is to investigate numerically the effect on the spreading and/or sliding of non-Newtonian fluid droplets on
Pregnancy-Related Mortality in the United States, 2011-2013.

OBJECTIVE To update national population-level pregnancy-related mortality estimates and examine characteristics and causes of pregnancy-related deaths in the United States during 2011-2013. METHODS We conducted an observational study using population-based data from the Pregnancy Mortality Surveillance System to calculate pregnancy-related mortality ratios by year, age group, and race-ethnicity groups. We explored 10 cause-of-death categories by pregnancy outcome during 2011-2013 and compared their distribution with those in our earlier reports since 1987. RESULTS The 2011-2013 pregnancy-related mortality ratio was 17.0 deaths per 100,000 live births. Pregnancy-related mortality ratios increased with maternal age, and racial-ethnic disparities persisted with non-Hispanic black women having a 3.4 times higher mortality ratio than non-Hispanic white women. Among causes of pregnancy-related deaths, the following groups contributed more than 10%: cardiovascular conditions ranked first (15.5%) followed by other medical conditions often reflecting pre-existing illnesses (14.5%), infection (12.7%), hemorrhage (11.4%), and cardiomyopathy (11.0%). Relative to the most recent report of Pregnancy Mortality Surveillance System data for 2006-2010, the distribution of cause-of-death categories did not change considerably. However, compared with serial reports before 2006-2010, the contribution of hemorrhage, hypertensive disorders of pregnancy, and anesthesia complications declined, whereas that of cardiovascular and other medical conditions increased (population-level percentage comparison). CONCLUSION The pregnancy-related mortality ratio and the distribution of the main causes of pregnancy-related mortality have been relatively stable in recent years.
Keratinocyte Differentiation-Dependent Human Papillomavirus Gene Regulation

Human papillomaviruses (HPVs) cause diseases ranging from benign warts to invasive cancers. HPVs infect epithelial cells and their replication cycle is tightly linked with the differentiation process of the infected keratinocyte. The normal replication cycle involves an early and a late phase. The early phase encompasses viral entry and initial genome replication, stimulation of cell division and inhibition of apoptosis in the infected cell. Late events in the HPV life cycle include viral genome amplification, virion formation, and release into the environment from the surface of the epithelium. The main proteins required at the late stage of infection for viral genome amplification include E1, E2, E4 and E5. The late proteins L1 and L2 are structural proteins that form the viral capsid. Regulation of these late events involves both cellular and viral proteins. The late viral mRNAs are expressed from a specific late promoter but final late mRNA levels in the infected cell are controlled by splicing, polyadenylation, nuclear export and RNA stability. Viral late protein expression is also controlled at the level of translation. This review will discuss current knowledge of how HPV late gene expression is regulated.