Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV‐1, HAART and cancer: A complex relationship

HIV infected people are at higher risk of developing cancer, although it is globally diminished in the era of highly active antiretroviral treatment (HAART). Recently, antioncogenic properties of some HAART drugs were discovered. We discuss the role of HAART in the prevention and improvement of treatment outcomes of cancers in HIV‐infected people. We describe different trends in HAART–cancer relationships: cancer‐predisposing as well as cancer‐preventing. We cover the roles of particular drug regimens in cancer prevention. We also describe the causes of cancer treatment with HAART drugs in HIV‐negative people, including ongoing clinical studies that may directly point to a possible independent anti‐oncogenic activity of HAART drugs. We conclude that despite potent antioncogenic activities of every class of HAART drugs reported in preclinical models, the evidence to date indicates that their independent clinical impact in HIV‐infected people is limited. Improved cancer prevention strategies besides HAART are needed to reduce HIV‐cancer‐related mortality.
THE BLOOD-BRAIN BARRIER (BBB) SCORE.

The blood-brain barrier (BBB) protects the brain from the toxic side-effects of drugs and exogenous molecules. However, it is crucial that medications developed for neurological disorders cross into the brain in therapeutic concentrations. Understanding the BBB interaction with drug molecules based on physicochemical property space can guide effective and efficient drug design. An algorithm, designated "BBB Score", composed of stepwise and polynomial piecewise functions, is herein proposed for predicting BBB penetration based on five physicochemical descriptors: number of aromatic rings, heavy atoms, MWHBN (a descriptor comprised of molecular weight, hydrogen bond donor and hydrogen bond acceptors), topological polar surface area and pKa. Based on statistical analyses of our results, the BBB Score outperformed (AUC = 0.86) currently employed MPO approaches (MPO: AUC = 0.61; MPO_V2: AUC = 0.67). Initial evaluation of physicochemical property space using the BBB Score is a valuable addition to currently available drug design algorithms.
6 mm short and 11 mm long implants compared in the full-arch rehabilitation of the edentulous mandible: a 3-year multicenter randomised controlled trial.

OBJECTIVE The aim of this multicenter parallel-group randomised controlled trial is to compare 6 mm short with 11 mm long implants in the rehabilitation of totally edentulous mandible in a completely comparable clinical situation, from anatomical, surgical and prosthetic point of view. MATERIAL AND METHODS 30 patients were selected in three study centers to receive a fixed full-arch mandibular rehabilitation supported by five interforaminal implants. Patients were randomly allocated, at the time of surgery, half to the test group (6 mm-length implants) and half to the control group (11 mm-length implants). No bone augmentation procedure was performed. After 3 months a screw-retained full-arch prosthesis with distal cantilevers was positioned (baseline). Peri-implant marginal bone level change (MBLc), implant and prosthesis survival rate and biological/technical complications were evaluated after 1 and 3 years. RESULTS 30 subjects (150 implants) were evaluated after 1 year and 28 (140 implants) after 3 years. No implant or prosthesis loss occurred. No significant inter-group difference for biological/technical complications was registered. No statistically significant (p>0.025) intra-group or inter-group difference in the mean MBLc values was registered. The mean MBLc were 0.01 ± 0.19 mm and -0.04 ± 0.21 mm at 1 year, and -0.10 ± 0.24 mm and 0.02 ± 0.25 mm at 3 years (test and control group, respectively). CONCLUSIONS 6 mm short implants may be a reliable option when used in the rehabilitation of total edentulous mandibles. These results need to be confirmed by longer follow-up data from well-designed randomised controlled clinical trials.
Rosuvastatin Attenuates acute nephrotoxicity through modulation of oxidative stress in Sprague Dawley rats.

Objective To assess the reno-protective effect of rosuvastatin on gentamicin-induced nephrotoxicity in rats. Methods The prospective experimental study was conducted at the College of Medicine, Mustansiriya University, Baghdad, Iraq, from March to July, 2018, and comprised Sprague Dawley male rats aged 3-4 months and weighing 200-400g each. The rats were divided into 3 equal groups which were treated for 14 days. Group1 was treated with distilled water plus normal saline, Group2 with distilled water plus gentamicin, and Group3 with rosuvastatin plus gentamicin. Parameters measured were blood urea, serum creatinine, serum malondialdehyde, superoxide dismutase, glutathione reductase, neutrophil gelatinase associated lipocalin, kidney injury molecule-1, interleukin- 18 and Cystatin-c. SPSS 20 was used for data analysis. Results Of the 30 rats, there were 10(33.3%) in each of the three groups. Rosuvastatin produced significant renoprotective effect through reduction of blood urea, kidney injury molecule-1 and interleukin-18 (p<0.01) compared to the gentamicin group. Conclusions Rosuvastatin was found to be a reno-protective against gentamicin-induced nephrotoxicity through modulation of pro-inflammatory and oxidative/anti-oxidant pathways.
Molecular and mechanical signals determine morphogenesis of the cerebral hemispheres in the chicken embryo

ABSTRACT During embryonic development, the telecephalon undergoes extensive growth and cleaves into right and left cerebral hemispheres. Although molecular signals have been implicated in this process and linked to congenital abnormalities, few studies have examined the role of mechanical forces. In this study, we quantified morphology, cell proliferation and tissue growth in the forebrain of chicken embryos during Hamburger-Hamilton stages 17-21. By altering embryonic cerebrospinal fluid pressure during development, we found that neuroepithelial growth depends on not only chemical morphogen gradients but also mechanical feedback. Using these data, as well as published information on morphogen activity, we developed a chemomechanical growth law to mathematically describe growth of the neuroepithelium. Finally, we constructed a three-dimensional computational model based on these laws, with all parameters based on experimental data. The resulting model predicts forebrain shapes consistent with observations in normal embryos, as well as observations under chemical or mechanical perturbation. These results suggest that molecular and mechanical signals play important roles in early forebrain morphogenesis and may contribute to the development of congenital malformations. Highlighted Article: Using experiments and modeling, this study illustrates the importance of not only chemical morphogen gradients, but also mechanical stress distributions, in embryonic development of the cerebral hemispheres.
Reno-protective effect of berberine.

Objective To assess the reno-protective effect of berberine on diclofenac-induced acute kidney injury in rats. Methods The experimental study was conducted at the College of Medicine, Mustansiriya University, Baghdad, Iraq, from January to March 2018, and comprised Sprague Dawley male rats which were divided into 3 equal groups. Group1 rats were treated with distilled water plus normal saline for 14 days, Group2 rats were treated with distilled water plus diclofenac for 14 days and Group3 rats were treated with berberine plus diclofenac for 14 days. Parameters measured were blood urea, serum creatinine, serum malondialdehyde, superoxide dismutase, glutathione reductase, neutrophil gelatinase associated lipocalin, kidney injury molecules-1, Interleukin-18and cystatin-c. Anthropometric measurements and estimated glomerular filtration rate were also noted. SPSS 20 was used for data analysis. Results Of the 30 rats, the three groups had 10(33.3%) each. Berberine reduced blood urea, serum creatinine, malondialdehyde, neutrophil gelatinase associated lipocalin, kidney injury molecules-1 and Interleukin-18 significantly compared to diclofenac-induced acute kidney injury (p<0.01 each). Berberine improved anti-oxidant capacity through significant elevation of superoxide dismutase and glutathione reductase sera levels (p<0.01 each). Conclusions Berberine was found to be an effective agent in the attenuation of diclofenac-induced acute kidney injury through the modulation of pro-inflammatory and oxidative stress biomarkers.
Genetically Increased Telomere Length and Aging-related Traits in the UK Biobank.

Telomere length (TL) shortens over time in most human cell types and is a potential biomarker of aging. However, the causal association of TL on physical and cognitive traits that decline with age has not been extensively examined in middle-aged adults. Using a Mendelian randomization (MR) approach, we utilized genetically increased TL (GI-TL) to estimate the causal association of TL on aging-related traits among UK Biobank (UKB) participants (age 40-69 years). We manually curated 53 aging-related traits from the UKB and restricted to unrelated participants of British ancestry (n=337,522). We estimated GI-TL as a linear combination of nine TL-associated SNPs, each weighted by its previously-reported association with leukocyte TL. Regression models were used to assess the associations between GI-TL and each trait. We obtained MR estimates using the two-sample inverse variance weighted (IVW) approach. We identified 6 age-related traits associated with GI-TL (Bonferroni-corrected threshold p < 0.001): pulse pressure (PP) (p=5.2x10-14), systolic blood pressure (SBP) (p=2.9x10-15), diastolic blood pressure (DBP) (p=5.5x10-6), hypertension (p=5.5x10-11), forced expiratory volume (FEV1) (p=0.0001), and forced vital capacity (FVC) (p=3.8x10-6). Under MR assumptions, one standard deviation increase in TL (~1200 base pairs) increased PP, SBP, and DBP by 1.5, 2.3, and 0.8 mmHg, respectively, while FEV1 and FVC increased by 34.7 and 52.2 mL, respectively. The observed associations appear unlikely to be due to selection bias based on analyses including inverse probability weights and analyses of simulated data. These findings suggest that longer TL increases pulmonary function and blood pressure traits among middle-aged UKB participants.
Learning Brain Effective Connectivity Network Structure Using Ant Colony Optimization Combining With Voxel Activation Information

Learning brain effective connectivity (EC) networks from functional magnetic resonance imaging (fMRI) data has become a new hot topic in the neuroinformatics field. However, how to accurately and efficiently learn brain EC networks is still a challenging problem. In this paper, we propose a new algorithm to learn the brain EC network structure using ant colony optimization (ACO) algorithm combining with voxel activation information, named as VACOEC. First, VACOEC uses the voxel activation information to measure the independence between each pair of brain regions and effectively restricts the space of candidate solutions, which makes many unnecessary searches of ants be avoided. Then, by combining the global score increase of a solution with the voxel activation information, a new heuristic function is designed to guide the process of ACO to search for the optimal solution. The experimental results on simulated datasets show that the proposed method can accurately and efficiently identify the directions of the brain EC networks. Moreover, the experimental results on real-world data show that patients with Alzheimers disease (AD) exhibit decreased effective connectivity not only in the intra-network within the default mode network (DMN) and salience network (SN), but also in the inter-network between DMN and SN, compared with normal control (NC) subjects. The experimental results demonstrate that VACOEC is promising for practical applications in the neuroimaging studies of geriatric subjects and neurological patients.
Label‐free superresolution effect of nonlinear reverse saturation absorption thin films through difference method

Label‐free superresolution effect of nonlinear reverse saturation absorption (NRSA) thin films was investigated through difference method, where a subdiffraction‐limit spot signal was constructed by intensity subtraction of two spots obtained under different laser intensities. By using annealed InSb films as the NRSA thin films, we experimentally obtained the subdiffraction‐limit spot signal, and the optimal reduction ratio was approximately 52.5% of the original spot. Experimental results agreed well with theoretical simulations. The simulation results of a 9‐point array sample showed the capability to achieve nonfluorescence superresolution imaging using the NRSA effect.
The effectiveness of a community-based, type 2 diabetes prevention programme on health-related quality of life. The DE-PLAN study

Background and aims The DE-PLAN was a European multicenter study, with the primary objective of testing whether a community-based lifestyle modification programme could serve as a means of primary prevention for type 2 diabetes (T2D) in high-risk individuals (based on the FINDRISC questionnaire). The aim of this study was to examine the impact of a 1-year community-based lifestyle intervention on health-related quality of life (HRQOL) in individuals from four participating European centers (Athens, Barcelona, Krakow, Kaunas), through a post-hoc analysis. Materials and methods Each center was allowed to implement different intervention strategies specifically tailored to the needs of their corresponding population sample. Before and after the intervention, participants underwent clinical evaluation, anthropometric measurements, an oral glucose tolerance test and lipid profile measurements. Health-related quality of life was assessed using the validated HRQOL-15D questionnaire. A difference of ±0.015 in the 15D questionnaire score was set as the threshold of clinically meaningful change. Results Data from 786 participants (67% females, mean age 59.7±9.4 years, BMI 31.5±4.5 kg/m2) with complete data regarding the HRQOL were analyzed (Athens: 104, Barcelona: 434, Krakow: 175, Kaunas: 70). After 1 year, a significant overall improvement in HRQOL was shown, as depicted by a change of 15D score from baseline value (0.88±0.9) to post-intervention (0.90±0.87, P<0.001), achieving the threshold of clinically meaningful change. A significant weight reduction was also observed (-0.8±4.0 kg, P<0.001). In multivariate analysis, improvement in HRQOL was independently associated with lower 15D score at baseline (P<0.001) and self-reported increase in overall exercise time (P<0.001) as assessed through specifically designed trial questionnaires. Conclusion A community-based lifestyle intervention programme aiming at T2D prevention, applied on a heterogeneous population and with varied methods, was shown to improve overall health-related quality of life to a clinically meaningful degree.
Perspectives of health professionals towards deprescribing practice in Asian nursing homes: a qualitative interview study

Objective To examine the determinants of deprescribing among health professionals in nursing homes, focusing on knowledge, practice and attitude. Design This was a qualitative study comprising semi-structured face-to-face interviews guided by 10 open-ended questions. Interviews were conducted until data saturation was achieved and no new ideas were formed. The interviews were audio-recorded, transcribed verbatim and analysed for themes. To derive themes, we employed directed content analysis of transcript data. Coding was completed using a combination of open, axial and selective coding. Setting Four nursing homes in Singapore. Participants The study involved 17 participants (comprising 4 doctors, 4 pharmacists and 9 nurses). Results Two key themes were identified, enablers and challenges. These were enablers and challenges faced by doctors, pharmacists and nurses towards deprescribing. The identified subthemes for enablers of deprescribing were: (1) awareness of medications that are unnecessary or could be targeted for deprescribing; (2) improving quality of life for patients with limited life expectancy; (3) improving communication between doctors, pharmacists and nurses; (4) systematic deprescribing practice and educational tools and (5) acknowledgement of possible benefits of deprescribing. The identified subthemes for challenges of deprescribing were: (1) symptoms not acknowledged as possibly drug-related; (2) lack of knowledge in patient’s and family members’ preferences; (3) lack of coordination between health professionals in hospitals and nursing homes and (4) limited tools for deprescribing. The development of a local guideline, mentoring nurses, case discussions, better shared decision-making and improving multidisciplinary communication, may help to support the process of deprescribing. Conclusion In conclusion, this study highlighted that deprescribing in the nursing homes is perceived by health professionals to be challenging and future research could assess how routine case studies, mentoring and better multidisciplinary communication could improve deprescribing knowledge and process in the nursing homes.
Radioactive iodine therapy for pediatric Graves’ disease: a single-center experience over a 10-year period

Abstract Introduction Only about 30% of pediatric patients with Graves’ hyperthyroidism achieve remission with medical therapy, and therefore radioactive iodine (RAI) therapy is often used as a definitive treatment. Although the goal of RAI is permanent hypothyroidism, this is not consistently achieved. We conducted a chart review to determine the factors associated with the success of RAI. We also tried to determine optimal follow-up post RAI and if there was an optimal L-thyroxine dose that would normalize the hypothyroid state quickly. Methods This is a retrospective chart review of Graves’ patients who underwent RAI between 2008 and 2017. We included age, sex, time from diagnosis, thyroid gland size, total dose of I-131 and dose in μCi/g of thyroid tissue. Patients were grouped based on outcome and analyzed using univariate and multivariate logistic regression. Follow-up thyroid levels post RAI and after starting l-thyroxine were analyzed. Results There were 78 ablations including six repeat ablations. Seventy-three percent became hypothyroid, 23% remained overtly or subclinically hyperthyroid, and 4% were euthyroid. Smaller thyroid size (36.5 vs. 47.4 g; p = 0.037) and higher dose of I-131 (242 vs. 212 μCi/g thyroid tissue; p = 0.013) were associated with a higher likelihood of hypothyroidism. Most patients remained hyperthyroid at 1 month post RAI, but by 3 months the majority became hypothyroid. There was no clear L-thyroxine dose that normalized hypothyroidism quickly. Conclusions An I-131 dose close to 250 μCi/g of thyroid tissue has a higher likelihood of achieving hypothyroidism. Testing at 2–3 months after RAI is most helpful to confirm response to RAI.
A functional regulatory variant of MYH3 influences muscle fiber-type composition and intramuscular fat content in pigs

Muscle development and lipid accumulation in muscle critically affect meat quality of livestock. However, the genetic factors underlying myofiber-type specification and intramuscular fat (IMF) accumulation remain to be elucidated. Using two independent intercrosses between Western commercial breeds and Korean native pigs (KNPs) and a joint linkage-linkage disequilibrium analysis, we identified a 488.1-kb region on porcine chromosome 12 that affects both reddish meat color (a*) and IMF. In this critical region, only the MYH3 gene, encoding myosin heavy chain 3, was found to be preferentially overexpressed in the skeletal muscle of KNPs. Subsequently, MYH3-transgenic mice demonstrated that this gene controls both myofiber-type specification and adipogenesis in skeletal muscle. We discovered a structural variant in the promotor/regulatory region of MYH3 for which Q allele carriers exhibited significantly higher values of a* and IMF than q allele carriers. Furthermore, chromatin immunoprecipitation and cotransfection assays showed that the structural variant in the 5′-flanking region of MYH3 abrogated the binding of the myogenic regulatory factors (MYF5, MYOD, MYOG, and MRF4). The allele distribution of MYH3 among pig populations worldwide indicated that the MYH3 Q allele is of Asian origin and likely predates domestication. In conclusion, we identified a functional regulatory sequence variant in porcine MYH3 that provides novel insights into the genetic basis of the regulation of myofiber type ratios and associated changes in IMF in pigs. The MYH3 variant can play an important role in improving pork quality in current breeding programs.
Risk Factors for Mortality Due to Ventilator-Associated Pneumonia in a Chinese Hospital: A Retrospective Study

Background As a common nosocomial infection, ventilator-associated pneumonia (VAP) often has high mortality. This study aimed to assess the risk factor for mortality owing to VAP. Material/Methods This retrospective clinical audit study screened medical records between the period of January 2014 and December 2017. All patients under mechanical ventilation MV) for ≥72 hours were screened against previously reported diagnostic criteria for VAP. The medical records were obtained for cases of documented diagnosis of VAP. Results In all, 145 patients (5.0%) diagnosed with VAP were included in the study; the morbidity of VAP was 19.5 episodes per 1000 days of MV. The 30-day mortality rate was 42.8%. Univariate logistic analysis showed that elevated neutrophil-to-lymphocyte ratio (NLR), high blood urea nitrogen/albumin (BUN/ALB) ratio, Multidrug-resistant organism infection, and a higher sequential organ failure assessment (SOFA) score were risk factors for mortality caused by VAP. In the second multivariate analysis, elevated NLR levels (P=0.038), high BUN/ALB ratio (P=0.016), multidrug-resistant organism infections (P=0.036), and a higher SOFA score (P<0.001) were still associated with the 30-day mortality rate. Conclusions The 30-day mortality rate of VAP was high. Blood NLR and BUN/ALB levels can be used as risk factors to assess the 30-day VAP-related mortality to help clinicians improve the prognosis of VAP.
Identification and characterization of primordial germ cells in a vocal learning Neoaves species, the zebra finch

The zebra finch has been used as a valuable vocal learning animal model for human spoken language. It is representative of vocal learning songbirds specifically, which comprise half of all bird species, and of Neoaves broadly, which comprise 95% of all bird species. Although transgenesis in the zebra finch has been accomplished, it is with a very low efficiency of germ‐line transmission and far from the efficiency with a more genetically tractable but vocal nonlearning species, the chicken (a Galloanseriformes). To improve germ‐line transmission in the zebra finch, we identified and characterized its primordial germ cells (PGCs) and compared them with chicken. We found striking differences between the 2 species, including that zebra finch PGCs were more numerous, more widely distributed in early embryos before colonization into the gonads, had slower timing of colonization, and had a different developmental gene‐expression program. We improved conditions for isolating and culturing zebra finch PGCs in vitro and were able to transfect them with gene‐expression vectors and incorporate them into the gonads of host embryos. Our findings demonstrate important differences in the PGCs of the zebra finch and advance the first stage of creating PGC‐mediated germ‐line transgenics of a vocal learning species. —Jung, K. M. , Kim, Y. M. , Keyte, A. L. , Biegler, M. T. , Rengaraj, D. , Lee, H. J., Mello, C. V. , Velho, T. A. F. , Fedrigo, O. , Haase, B. , Jarvis, E. D. , Han, J. Y. Identification and characterization of primordial germ cells in a vocal learning Neoaves species, the zebra finch. FASEB J. 33, 13825‐13836 (2019). www.fasebj. org