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The sequence of the DNA contains coding and non-coding regions. The role of the non-coding regions is not known and is hypothesized to maintain the structure of the DNA. This study aimed to investigate the structure of the non-coding sequences in honey bees utilizing bioinformatics. The non-coding sequences of the mtDNA of three honey bee species Apis dorosata, Apis florea, Apis cerana, and ten subspecies of Apis mellifera were investigated. Different techniques were utilized to explore the non-coding regions of these bees including sequence analysis, phylogenetic relationships, enzymatic digestion, and statistical tests. Variations in size and sequences of nucleotides were detected in the studied species and subspecies, but with the same nucleotide abundance (i.e. nucleotides A were more than T and nucleotides G were less than C). The phylogenetic tree based on the non-coding regions was partially similar to the known phylogenetic relationships between these bees. The enzymatic digestion using four restriction enzymes confirmed the results of the phylogenetic relationships. The statistical analysis based on numerical codes for nucleotides showed the absence of significant variations between the studied bees in their sequences in a similar way to results of neutrality tests. This study suggests that the non-coding regions have the same functional role in all the studied bees regardless of the number of nucleotides, and not just to maintain the structure of the DNA. This is approximately the first study to shade lights on the non-coding regions of the mtDNA of honey bees.

DNA hybridization-capture techniques allow researchers to focus their sequencing efforts on preselected genomic regions. This feature is especially useful when analys- ing ancient DNA (aDNA) extracts, which are often dominated by exogenous environ- mental sources. Here, we assessed, for the first time, the performance of hyRAD as an inexpensive and design-free alternative to commercial capture protocols to obtain authentic aDNA data from osseous remains. HyRAD relies on double enzymatic re- striction of fresh DNA extracts to produce RNA probes that cover only a fraction ofthe genome and can serve as baits for capturing homologous fragments from aDNA li- braries. We found that this approach could retrieve sequence data from horse remains coming from a range of preservation environments, including beyond radiocarbon range, yielding up to 146.5-fold on-target enrichment for aDNA extracts showing ex- tremely low endogenous content (20%¿30%), while the fraction of endogenous reads mapping on- and off-target was relatively insensi- tive to the original endogenous DNA content. Procedures based on two instead of a single round of capture increased on-target coverage up to 3.6-fold. Additionally, we used methylation-sensitive restriction enzymes to produce probes targeting hypo- methylated regions, which improved data quality by reducing post-mortem DNA dam- age and mapping within multicopy regions. Finally, we developed a fully automated hyRAD protocol utilizing inexpensive robotic platforms to facilitate capture process- ing. Overall, our work establishes hyRAD as a cost-effective strategy to recover a set of shared orthologous variants across multiple ancient samples., This project received funding from: the University Paul Sabatier IDEX Chaire d’Excellence (OURASI); the CNRS Programme de Recherche Conjoint (PRC); the CNRS International Research Project (IRP AMADEUS); the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 797449; the Russian Foundation for Basic Research, project No. 19-59-15001 “Horses and their importance in the life of the ancient population of Altai and adjacent territories: interdisciplinary research and reconstruction”; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement 681605).

Aedes mosquitoes are the most important group of vectors that transmit pathogens, including arboviruses, and cause human diseases such as dengue fever, yellow fever, Zika virus, and Chikungunya. Biosynthesis and the use of green silver nanoparticles (AgNPs) is a vital step to identify reliable and eco-friendly controls for these vectors. In this study, Aedes (Ae.) aegypti larvae (2nd and 3rd instar) were exposed to leaf extracts of Ricinus communis (Castor) and AgNPs synthesized from the extract to evaluate their larvicidal potential. Synthesized AgNPs were characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and energy-dispersive X-ray spectroscopy (XRD). Ae. aegypti larvae were treated with different concentrations (50–250 ppm) of the leaf extract and synthesized AgNPs. There were five replicates per treatment, in addition to a positive (temephos) and negative control (dechlorinated water). Mortality was recorded after 12, 24, 36, and 48 h and the data were subjected to Probit analysis. The nanoparticles were more toxic (LC50 = 46.22 ppm and LC90 = 85.30 ppm) than the plant extract (106.24 and 175.73 ppm, respectively). The leaf extracts of Ricinus communis were subjected to HPLC analysis to identify their chemical constituents. This study suggests that plant extracts and synthesized nanoparticles are excellent alternatives to hazardous chemical pesticides used to control vector mosquitoes. This is a potentially useful technique that can reduce aquatic toxicity from insecticide use.

Purpose The microRNAs expression has emerged as a potential biomarker for the diagnosis and prognosis of prostate cancer. This study investigated the expression of miRNA-182 and miRNA-187 in prostate cancer patients and established a correlation between miRNA expression and staging of prostate cancer. Materials and Methods This prospective observational study involved patients undergoing transrectal ultrasound-guided biopsy for suspicion of prostate cancer. Pre-biopsy urine samples and prostatic core tissue samples of the patients were preserved and the miRNA-182 and miRNA-187 were studied. Results Sixty-three patients were included in this study, thirty-three patients were diagnosed with prostate cancer and thirty patients having benign histopathology were considered as controls. The expression of miRNA-182 was significantly increased (p=0.002) and miRNA-187 significantly decreased (p

Cellular secreted proteins (secretome), together with cellular membrane proteins, collectively referred to as secretory and membrane proteins (SMPs) are a large potential source of biomarkers as they can be used to indicate cell types and conditions. SMPs have been shown to be ideal candidates for several clinically approved drug regimens including for cancer. This study aimed at performing a functional analysis of SMPs within different cancer subtypes to provide great clinical targets for potential prognostic, diagnostic and the therapeutics use. Using an innovative majority decision-based algorithm and transcriptomic data spanning 5 cancer types and over 3000 samples, we quantified the relative difference in SMPs gene expression compared to normal adjacent tissue. A detailed deep data mining analysis revealed a consistent group of downregulated SMP isoforms, enriched in hematopoietic cell lineages (HCL), in multiple cancer types. HCL-associated genes were frequently downregulated in successive cancer stages and high expression was associated with good patient prognosis. In addition, we suggest a potential mechanism by which cancer cells suppress HCL signaling by reducing the expression of immune-related genes. Our data identified potential biomarkers for the cancer immunotherapy. We conclude that our approach may be applicable for the delineation of other types of cancer and illuminate specific targets for therapeutics and diagnostics.

Alongside horses, donkeys and their first-generation hybrids represent members of the Equidae family known for their social, economic and symbolic importance in protohistoric and historical France. However, their relative importance and their respective roles in different regions and time periods are difficult to assess based on textual, iconographic and archaeological evidence. This is both due to incomplete, partial and scattered historical sources and difficulties to accurately assign fragmentary archaeological remains at the proper taxonomic level. DNA- based methods, however, allow for a robust identification of the taxonomic status of ancient equine osseous material from minimal sequence data. Here, we leveraged shallow ancient DNA sequencing and the dedicated Zonkey computational pipeline to obtain the first baseline distribution for horses, mules and donkeys in France from the Iron Age to the Modern period. Our collection includes a total of 873 ancient specimens spanning 128 sites and comprising 717 horses, 100 donkeys, 55 mules and a single hinny individual. While horses were ubiquitous and the most dominant species identified, our dataset reveals the importance of mule breeding during Roman times, especially between the 1st and 3rd centuries CE (Common Era), where they represented between 20.0% and 34.2% of equine assemblages. In contrast, donkeys were almost absent from northern France as- semblages during the whole Roman period, but replaced mules in rural and urban commercial and economic centers from the early Middle Ages. Our work also identified donkeys of exceptional size during Late Antiquity, which calls for a deep reassessment of the true morphological space of past equine species. This study confirmed the general preference toward horses throughout all time periods investigated but revealed dynamic manage- ment strategies leveraging the whole breadth of equine resources in various social, geographic and temporal contexts., Pierre Clavel’s PhD position is funded by the CNRS MITI interdisciplinary programme (Mission pour les Initiatives Transverses et Interdisciplinaires). Xuexue Liu was supported by the European Union’s Horizon 2020 research and Innovation programme under the Marie Skłodowska-Curie grant agreement 101027750. Andaine Seguin-Orlando acknowledges IAST for funding from ANR under grant ANR-17-EURE-0010 (Investissements d’Avenir programme). This work was supported by the France G ́enomique Appel `a Grand Projet (ANR-10-INBS-09-08, BUCEPHALE project); the Initiative d’Excellence Chaires d’attractivit ́e, Universit ́e de Toulouse (OURASI) and the Villum Fonden miGENEPI research project. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 681605)

The maximum quantum yield of photosystem II (as reflected by variable to maximum chlorophyll a fluorescence, Fv /Fm ) is regarded as one of the most important photosynthetic parameters. The genetic basis underlying natural variation in Fv /Fm , which shows low level of variations in plants under non-stress conditions, is not easy to be exploited using the conventional gene cloning approaches. Thus, in order to answer this question, we have followed another strategy: we used genome-wide association study (GWAS) and transgenic analysis in a rice mini-core collection. We report here that four single-nucleotide polymorphisms, located in the promoter region of β-glucosidase 5 (BGlu-5), are associated with observed variation in Fv /Fm . Indeed, our transgenic analysis showed a good correlation between BGlu-5 and Fv /Fm . Thus, our work demonstrates the feasibility of using GWAS to study natural variation in Fv /Fm , suggesting that cis-element polymorphism, affecting the BGlu-5 expression level, may, indirectly, contribute to Fv /Fm variation in rice through the gibberellin signaling pathway. Further research is needed to understand the mechanism of our novel observation.

Domestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 bc3. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture., The work by G. Boeskorov is done on state assignment of DPMGI SB RAS. This project was supported by the University Paul Sabatier IDEX Chaire d’Excellence (OURASI); Villum Funden miGENEPI research programme; the CNRS ‘Programme de Recherche Conjoint’ (PRC); the CNRS International Research Project (IRP AMADEUS); the France Génomique Appel à Grand Projet (ANR-10-INBS-09-08, BUCEPHALE project); IB10131 and IB18060, both funded by Junta de Extremadura (Spain) and European Regional Development Fund; Czech Academy of Sciences (RVO:67985912); the Zoological Institute ZIN RAS (АААА-А19-119032590102-7); and King Saud University Researchers Supporting Project (NSRSP–2020/2). The research was carried out with the financial support of the Russian Foundation for Basic Research (19-59-15001 and 20-04-00213), the Russian Science Foundation (16-18-10265, 20-78-10151, and 21-18-00457), the Government of the Russian Federation (FENU-2020-0021), the Estonian Research Council (PRG29), the Estonian Ministry of Education and Research (PRG1209), the Hungarian Scientific Research Fund (Project NF 104792), the Hungarian Academy of Sciences (Momentum Mobility Research Project of the Institute of Archaeology, Research Centre for the Humanities); and the Polish National Science Centre (2013/11/B/HS3/03822). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie (grant agreement 797449). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreements 681605, 716732 and 834616).

Background The aim of this study was to determine the frequency of coronary artery anomalies (CAAs) in Tetralogy of Fallot (TOF) patients undergoing computed tomography (CT)-angiography in a tertiary care hospital. Methodology In this observational study, we included consecutive TOF patients undergoing CT-angiography without prior history of cardiac surgery or congenital heart disease. CAAs were defined based on either origin or course of the artery. Results Out of 441 TOF patients, the prevalence of CCAs was 3.6% (16), of which 13 were below 18 years of age. Anomalous left main artery was observed in six (1.4%) patients, followed by left anterior descending artery and right coronary artery, observed in four (0.9%) patients each, and two (0.5%) patients had a single coronary artery originating from the left coronary cusp with an interarterial course. Conclusions CAAs were observed in a significant number (3.6%) of TOF patients. A CT-angiographic assessment before surgical correction would help identify the exact anatomy for better surgical planning to minimize complications.

Background In underdeveloped countries, coronary artery disease (CAD) has developed into a serious health issue due to the high rates of risk factors such as obesity and smoking amongst the population. This study has been performed to find the rate of multivessel CAD (MVD) and subsequent thrombolysis in myocardial infarction (TIMI) flow grade III in patients undergoing primary percutaneous coronary intervention (PCI). Methods This transverse study was carried out involving 110 patients from the emergency department of the National Institute of Cardiovascular Diseases, Karachi, Pakistan, from August 2015 to March 2016. All patients were diagnosed as ST-segment elevation myocardial infarction (STEMI) and had gone through primary PCI. Pre-procedure angiographic findings regarding the number of vessels involved and post-procedure TIMI flow grade were assessed and analysed. Results The average age of the study sample was 56.3 ± 11.4 years. The proportion of male patients was 81.8% (n=90), and hypertension was the most prevalent risk factor followed by type II diabetes with a frequency of 67.3% (n=74) and 40.0% (n=44), respectively. Coronary angiography showed MVD in 50.0% (n=55) of the patients, of whom 34 patients had two-vessel disease, and the remaining 21 had three-vessel disease. Ninety percent (n=99) of the patients exhibited TIMI flow grade III after the procedure with no significant difference between patients with MVD and those with single-vessel disease with a rate of 87.3% (n=48/55) versus 92.7% (n=51/55, P=0.527), respectively. Conclusion Post-procedure TIMI flow grade III was accomplished in almost 90% of the subjects with or without MVD. It can be concluded that primary PCI has a significant role in the early restoration of myocardial blood flow following STEMI regardless of the vessels involved.

Most cancer care is delivered in the community, while most clinical trials exist in academic centers. We analyzed clinical trial accrual of a tertiary care cancer center and its affiliated community sites to better understand what types of trials accrued at the community sites and whether community accrual increased ethnic diversity. The institutional clinical trial database was searched for solid tumor accruals during 2018–2019. Patient’s race was abstracted, and trial’s funding source, phase, and disease type/stage were tabulated. Of 3689 accruals, 133 were at community sites, representing 26 unique trials while the main campus accrued to 93 unique trials. Community site accruals were highest for breast and colorectal cancer, but patients with less common cancers such as renal, nasopharyngeal, and gastric cancer were also accrued at community sites. Accruals occurred to randomized trials, as well as phase Ib and translational biomarker studies. Minority patients constituted 20.0% and 32.5% of community site accruals for therapeutic and non-therapeutic trials respectively, compared to 20.6% and 29.8% of main campus accruals for therapeutic and non-therapeutic trials, respectively. We conclude that community sites affiliated with an academic cancer center can accrue to a broad spectrum of clinical trials while enhancing racial diversity in participation of clinical trials. Further expansion of access to clinical trials in community sites is necessary to broaden patient access to state-of-the-art and next-generation treatment options.

Non-photochemical quenching (NPQ) of the excited state of chlorophyll a is a major photoprotective mechanism plants utilize to survive under high light. Here, we report the impact of long-term light quality treatment on photosynthetic properties, especially NPQ in rice. We used three LED-based light regimes, i.e., red (648–672 nm), blue (438–460 nm), and “warm” white light (529–624 nm), with the incident photon flux density of 300 µmol photons m−2 s−1, the difference in the absorbed photon flux densities by leaves grown under different light quality being less than 7%. Our results show that blue light, as compared to white light, induced a significant decrease in Fv/Fm, a decreased rate of reduction of P700+ after P700 was completely oxidized; furthermore, blue light also induced higher NPQ with an increased initial speed of NPQ induction, which corresponds to the qE component of NPQ, and a lower maximum quantum yield of PSII, i.e., Y(II). In contrast, rice grown under long-term red light showed decreased Y(II) and increased NPQ, but with no change in Fv/Fm. Furthermore, we found that rice grown under either blue or red light showed decreased transcript abundance of both catalase and ascorbate peroxidase, together with an increased H2O2 content, as compared to rice grown under white light. All these data suggest that even under a moderate incident light level, rice grown under blue or red light led to compromised antioxidant system, which contributed to decreased quantum yield of photosystem II and increased NPQ.

BACKGROUND: Gastric subepithelial lesions are frequently encountered during endoscopic examinations, and the majority of them are small and asymptomatic. Among these lesions, gastrointestinal stromal tumors (GISTs) are the major concern for patients and clinicians owing to their malignant potentials. Although previous guidelines suggested periodic surveillance for such small (≤ 20 mm) lesions, several patients and clinicians have still requested or prescribed repeated examinations or radical resection, posing extra medical burdens and risks. AIM: To describe the clinical course of suspected small gastric GISTs and provide further evidence for surveillance strategy for tumor therapy. METHODS: This single-center, retrospective study was conducted at West China Hospital, Sichuan University. Consecutive patients with suspected small gastric GISTs were reviewed from November 2004 to November 2018. GIST was suspected according to endoscopic ultrasonography features: hypoechoic lesions from muscularis propria or muscularis mucosa. Eligible patients with suspected small (≤ 20 mm) GISTs were included for analysis. Patients’ demographic data, lesions’ characteristics, and follow-up medical records were collected. RESULTS: A total of 383 patients (male/female, 121/262; mean age, 54 years) with 410 suspected small gastric GISTs (1 lesion in 362 patients, 2 lesions in 16, 3 lesions in 4, and 4 lesions in 1) were included for analysis. The most common location was gastric fundus (56.6%), followed by body (29.0%), cardia (12.2%), and antrum (2.2%). After a median follow-up of 28 mo (interquartile range, 16-48; range, 3-156), 402 lesions (98.0%) showed no changes in size, and size of 8 lesions (2.0%) was increased (mean increment, 10 mm). Of the 8 lesions with size increment, endoscopic or surgical resection was performed in 6 patients (5 GISTs and 1 leiomyoma). For other 2 remaining patients, unroofing biopsy or endoscopic ultrasound-guided fine-needle aspiration was carried out (2 GISTs), while no further change in size was noted over a period of 62-64 mo. CONCLUSION: The majority of suspected small (≤ 20 mm) gastric GISTs had no size increment during follow-up. Regular endoscopic follow-up without pathological diagnosis may be highly helpful for such small gastric subepithelial lesions.

The accurate detection of changes has the potential to form a fundamental component of systems which autonomously solicit user interaction based on transitions within an input stream, for example, electrocardiogram data or accelerometry obtained from a mobile device. This solicited interaction may be utilized for diverse scenarios such as responding to changes in a patient's vital signs within a medical domain or requesting user activity labels for generating real-world labelled datasets. Within this paper, we extend our previous work on the Multivariate Online Change detection Algorithm subsequently exploring the utility of incorporating the Benjamini Hochberg method of correcting for multiple comparisons. Furthermore, we evaluate our approach against similarly light-weight Multivariate Exponentially Weighted Moving Average and Cumulative Sum based techniques. Results are presented based on manually labelled change points in accelerometry data captured using 10 participants. Each participant performed nine distinct activities for a total period of 35 minutes. The results subsequently demonstrate the practical potential of our approach from both accuracy and computational perspectives.

Cyclin-dependent kinases 4 and 6 (CDK4/6) are fundamental drivers of the cell cycle and are required for the initiation and progression of various malignancies. Pharmacological inhibitors of CDK4/6 have shown significant activity against several solid tumours. Their primary mechanism of action is thought to be the inhibition of phosphorylation of the retinoblastoma tumour suppressor, inducing G1 cell cycle arrest in tumour cells. Here we use mouse models of breast carcinoma and other solid tumours to show that selective CDK4/6 inhibitors not only induce tumour cell cycle arrest, but also promote anti-tumour immunity. We confirm this phenomenon through transcriptomic analysis of serial biopsies from a clinical trial of CDK4/6 inhibitor treatment for breast cancer. The enhanced anti-tumour immune response has two underpinnings. First, CDK4/6 inhibitors activate tumour cell expression of endogenous retroviral elements, thus increasing intracellular levels of double-stranded RNA. This in turn stimulates production of type III interferons and hence enhances tumour antigen presentation. Second, CDK4/6 inhibitors markedly suppress the proliferation of regulatory T cells. Mechanistically, the effects of CDK4/6 inhibitors both on tumour cells and on regulatory T cells are associated with reduced activity of the E2F target, DNA methyltransferase 1. Ultimately, these events promote cytotoxic T-cell-mediated clearance of tumour cells, which is further enhanced by the addition of immune checkpoint blockade. Our findings indicate that CDK4/6 inhibitors increase tumour immunogenicity and provide a rationale for new combination regimens comprising CDK4/6 inhibitors and immunotherapies as anti-cancer treatment.

Objective: To compare surgical outcomes of acute acetabular transverse fracture using ilioinguinal and Stoppa approach. Methods: Twenty five patients who managed with ilioinguinal approach (group A) at a mean follow-up of (32.3±4.6) mo and 30 patients who managed with Stoppa approach (group B) at a mean follow-up of (29.7±3.8) mo were prospectively reviewed. The study was approved by the hospital ethical review committee (IRB approval no: 0189-2007). Patients were called for routine follow up and follow-up durations were set. End points of the study were: (1) blood loss was measured intraoperatively by measuring the blood loss in the suction drain and counting blood stained gauze and postoperatively by assessing hemoglobin after 6 h of surgery; (2) functional outcome was demonstrated using the Harris hip score; (3) reduction quality and radiological results were demonstrated by Matta scoring system. Results: Mean blood loss (intraoperatively + postoperatively) was (1 175.8±310.2) mL and (1 115.7±285.1) mL in patients operated with ilioinguinal and Stoppa approach, respectively. Mean operative time was (242.3±60.8) min and (198.9±50.3) min in patients operated with ilioinguinal and Stoppa approach, respectively. Functional outcome, radiological outcome and reduction quality showed no significant difference between two approaches. Complication rate was 36.0% in group A (9 patients) and 13.3% in group B (4 patients). Conclusions: Our study concludes that Stoppa approach allows less blood loss and operative time with fewer complications.

Summary Horse domestication revolutionized warfare and accelerated travel, trade, and the geographic expansion of languages. Here, we present the largest DNA time series for a non-human organism to date, including genome-scale data from 149 ancient animals and 129 ancient genomes (≥1-fold coverage), 87 of which are new. This extensive dataset allows us to assess the modern legacy of past equestrian civilizations. We find that two extinct horse lineages existed during early domestication, one at the far western (Iberia) and the other at the far eastern range (Siberia) of Eurasia. None of these contributed significantly to modern diversity. We show that the influence of Persian-related horse lineages increased following the Islamic conquests in Europe and Asia. Multiple alleles associated with elite-racing, including at the MSTN “speed gene,” only rose in popularity within the last millennium. Finally, the development of modern breeding impacted genetic diversity more dramatically than the previous millennia of human management., Graphical Abstract, Highlights • Two now-extinct horse lineages lived in Iberia and Siberia some 5,000 years ago • Iberian and Siberian horses contributed limited ancestry to modern domesticates • Oriental horses have had a strong genetic influence within the last millennium • Modern breeding practices were accompanied by a significant drop in genetic diversity, Genome-wide data from 278 ancient equids provide insights into how ancient equestrian civilizations managed, exchanged, and bred horses and indicate vast loss of genetic diversity as well as the existence of two extinct lineages of horses that failed to contribute to modern domestic animals.

Globally, every day, ∼2,300 children and adolescents succumb to unintentional injuries sustained from motor vehicle collisions, drowning, poisoning, falls, burns, and violence. The rate of deaths due to motor vehicle injuries in adolescents is 10.2 per 100,000 adolescents. We systematically reviewed published evidence to identify interventions to prevent unintentional injuries among adolescents aged 11–19 years. We defined unintentional injuries as a subset of injuries for which there was no evidence of predetermined intent, and the definition included motor vehicle injuries, suffocation, drowning, poisoning, burns, falls, and sports and recreation. Thirty-five studies met study eligibility criteria. The included studies focused on interventions to prevent motor vehicle injuries and sports-related injuries. Results suggest that possession of a graduated driver license (GDL) significantly reduced road accidents by 19% (relative risk [RR]: .81; 95% confidence interval [CI]: .75–.88; n = 5). There was no impact of GDL programs on incidence of injuries (RR: .78; 95% CI: .57–1.06; n = 2), helmet use (RR: 1.0; 95% CI: .98–1.02; n = 3), and seat belt use (RR: .99; 95% CI: .97–1.0; n = 3). Sports-related injury prevention interventions led to reductions in the incidence of injuries (RR: .66; 95% CI: .53–.82; n = 15), incidence of injury per hour of exposure (RR: .63; 95% CI: .47–.86; n = 5), and injuries per number of exposures (RR: .79; 95% CI: .70–.88; n = 4). Subgroup analysis according to the type of interventions suggests that training ± education and the use of safety equipment had significant impacts on reducing the incidence of injuries. We did not find any study focusing on interventions to prevent suffocation, drowning, poisoning, burns, and falls in the adolescent age group. The existing evidence is mostly from high-income countries, limiting the generalizability of these findings for low- and middle-income countries. Studies evaluating these interventions need to be replicated in a low- and middle-income country–context to evaluate effectiveness with standardized outcome measures.

This report reveals the effects of salt on the photosynthetic electron transport and transcriptome of the glycophyte Setaria viridis (S. viridis) and its salt-tolerant close relative halophyte Spartina alterniflora (S. alterniflora). S. viridis was unable to survive exposed to sodium chloride (NaCl) levels higher than 100 mM, in contrast, S. alterniflora could tolerate NaCl up to 550 mM, with negligible effect on gas exchange related parameters and conductance of electrons transport chain (gETC). Under salt, the prompt fluorescence (OJIP-curves) exhibits an increase in the O- and J-steps in S. viridis and much less for S. alterniflora. Flowing NaCl stress, a dramatic decline in the photosystem II (PSII) primary photochemistry was observed for S. viridis, as reflected by the drastic drop in Fv/Fm, Fv/Fo and ΦPSII; however, no substantial change was recorded for these parameters in S. alterniflora. Interestingly, we found an increase in the primary PSII photochemistry (ΦPSII) for S. alterniflora with increasing either NaCl concentration or NaCl treatment duration. The NPQ magnitude was strongly enhanced for S. viridis even at a low NaCl (50 mM); however, it remains unchangeable or slightly increased for S. alterniflora at NaCl levels above 400 mM. After NaCl treatment, we found an increase in both the proportion of oxidized P700 and the amount of active P700 in S. viridis and almost no change for S. alterniflora. Under salt, the net photosynthetic rate (A) and stomatal conductance (gs) measurements demonstrate that A decreases earlier in S. viridis, even after one week exposure to only 50 mM NaCl; in contrast, in S. alterniflora, the effect of NaCl on A and gs was minor even after exposure for two weeks to high NaCl levels. For S. viridis exposed to 50 mM NaCl for 12 d, carbon dioxide (CO2) at a concentration of 2000 μL L−1 could not fully restore A to the control (Ctrl) level. Conversely, in S. alterniflora, high CO2 can fully restore A for all NaCl treatments except at 550 mM. RNA-seq data shows a major impact of NaCl on metabolic pathways in S. viridis and we found a number of transcription factors potentially related to NaCl responses. For S. alterniflora, no major changes in the transcriptomic levels were recorded under NaCl stress. To confirm our data analysis of RNA-seq, we performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis for randomly selected four genes for each species (8 genes in total) and we found that our results (up- and/or down-regulated genes) are fully consistent and match well our RNA-seq data. Overall, this study showed drastically different photosynthetic and transcriptomic responses of a salt-tolerant C4 grass species and one salt-sensitive C4 grass species to NaCl stress, which suggests that S. alterniflora could be used as a promising model species to study salt tolerance in C4 or monocot species.

The advent of new devices, technology, machine learning techniques, and the availability of free large speech corpora results in rapid and accurate speech recognition. In the last two decades, extensive research has been initiated by researchers and different organizations to experiment with new techniques and their applications in speech processing systems. There are several speech command based applications in the area of robotics, IoT, ubiquitous computing, and different human-computer interfaces. Various researchers have worked on enhancing the efficiency of speech command based systems and used the speech command dataset. However, none of them catered to noise in the same. Noise is one of the major challenges in any speech recognition system, as real-time noise is a very versatile and unavoidable factor that affects the performance of speech recognition systems, particularly those that have not learned the noise efficiently. We thoroughly analyse the latest trends in speech recognition and evaluate the speech command dataset on different machine learning based and deep learning based techniques. A novel technique is proposed for noise robustness by augmenting noise in training data. Our proposed technique is tested on clean and noisy data along with locally generated data and achieves much better results than existing state-of-the-art techniques, thus setting a new benchmark.

Bacillus pumilus strain SCAL1 is an endophytic, thermophilic plant that was isolated from the leaf of a plant, Solanum lycopersicum L., in Sindh, Pakistan. B. pumilus strain SCAL1 has usually exhibited high resistance to environmental stresses, with a growth temperature ranging from 30 to 60°C. An approximately 3.75-Mb draft genome was assembled into 68 contigs. This research was supported by Department of Biological Sciences, Thompson Rivers University, Canada. We thank Jonathan D. Van Hamme, Department of Biological Sciences, Thompson Rivers University, for sequencing B. pumilus SCAL1 and assisting with data analysis. We thank Rachel Backer, Department of Plant Science, McGill University, for assistance with English language revisions.

To assess the functional outcome of acute primary total hip replacement in the management of complex acetabular fractures. This prospective observational study was conducted in orthopedic department of Liaquat National Hospital and Medical College, Karachi. The study was approved by the Ethics review committee of hospital (0190-2016). Patients who encountered between January 2010 to January 2016 were entered. Fifty-four patients with acetabular fractures with certain indications (marginal impaction or significant comminution (> 3 fragments) of the articular surface of the acetabulum, full-thickness articular injury to the femoral head, an associated femur neck fracture, or preexisting symptomatic osteoarthritis) were treated with primary total hip replacement. Patients were followed in outpatient clinic at regular intervals after discharge to assess the radiological union of fractures and complications. Functional outcome was evaluated after 2 years by applying Harris Hip Score. All statistical analysis was done by using SPSS version 20. All patients achieved radiological union of fractures at an average duration of 21 weeks. During the follow-up, seven complications were observed. Two patients developed superficial surgical site infection which was treated conservatively. One patient had dislocation which was reduced closely, while two patients had acetabular cup loosening which was revised. We also observed two cases of Brooker I heterotopic ossification and one case of Brooker II. At 2-year follow-up, 78% of patients had an excellent and good functional outcome according to Harris Hip score. Primary total hip replacement is a valid and reasonable one stage surgical treatment of complex acetabular fractures and in aged individuals. However, the complications are not uncommon.

Ancient genomics of horse domestication The domestication of the horse was a seminal event in human cultural evolution. Librado et al. obtained genome sequences from 14 horses from the Bronze and Iron Ages, about 2000 to 4000 years ago, soon after domestication. They identified variants determining coat color and genes selected during the domestication process. They could also see evidence of admixture with archaic horses and the demography of the domestication process, which included the accumulation of deleterious variants. The horse appears to have undergone a different type of domestication process than animals that were domesticated simply for food. Science , this issue p. 442

A monochorionic-diamniotic twin baby presented with intrauterine growth restriction and anuria. The baby was found to have bladder agenesis, a pelvic dysplastic horseshoe kidney, vertebral anomalies, a ventricular septal defect and facial dysmorphisms. It was surprising to find no abnormalities in amniotic fluid indices prenatally, suggesting the possibility of urine output that declined as the pregnancy proceeded. Some degree of twin-to-twin transfusion of amniotic fluid was also possible, which could have rescued the oligohydramnios known to be associated with kidney and urinary tract abnormalities. It was also notable that there was no abnormality in respiratory function, especially since further investigations revealed close to no kidney function. The intrauterine growth restriction (IUGR) along with the multiple anomalies found made the baby unsuitable for dialysis and transplant, and the decision of transition to palliative care was made.

Rationale: Delayed perforation of duodenal endoscopic submucosal dissection (ESD) was reported to be up to 14.3%. High invasive surgery remains the main treatment for delayed duodenal perforation. Patient concerns: A 56-year-old woman presented with abdominal pain and fever at 1st day after ESD for treating a large laterally spreading tumor in the second part of duodenum. Diagnosis: Emergent abdominal computed tomography revealed the presence of duodenal perforation. Interventions: Endoscopic purse-string technique was used to partially close the large mucosal defect. Percutaneous endoscopic gastrostomy was conducted for gastric drainage and proximal drainage of the wound. A nasointestinal decompression tube was placed for distal drainage of the wound. Outcomes: No further symptoms were noted after 5 days. Both upper gastrointestinal series and endoscopy confirmed the healing of the wound. Lessons: Partial closure of the mucosal defect followed by adequate drainage can be selected as a preferred choice for management of delayed duodenal perforation. It may also serve as an alternative for prevention of delayed perforation when complete closure of the mucosal defect is technically difficult or impossible.

The horse was domesticated only 5.5 KYA, thousands of years after dogs, cattle, pigs, sheep, and goats. The horse nonetheless represents the domestic animal that most impacted human history; providing us with rapid transportation, which has considerably changed the speed and magnitude of the circulation of goods and people, as well as their cultures and diseases. By revolutionizing warfare and agriculture, horses also deeply influenced the politico-economic trajectory of human societies. Reciprocally, human activities have circled back on the recent evolution of the horse, by creating hundreds of domestic breeds through selective programs, while leading all wild populations to near extinction. Despite being tightly associated with humans, several aspects in the evolution of the domestic horse remain controversial. Here, we review recent advances in comparative genomics and paleogenomics that helped advance our understanding of the genetic foundation of domestic horses.

Structure-based 3D-QSAR study was performed on a class of 5-benzylidene-2-phenylthiazolinones non-redox type 5-LOX inhibitors. In this study, binding pocket of 5-Lipoxygenase (pdb id 3o8y) was identified by manual docking using 15-LOX (pdb id 2p0m) as a reference structure. Additionally, most of the binding site residues were found conserved in both structures. These non-redox inhibitors were then docked into the binding site of 5-LOX. To generate reliable CoMFA and CoMSIA models, atom fit data base alignment method using docked conformation of the most active compound was employed. The q(2)cv and r(2)ncv values for CoMFA model were found to be 0.549 and 0.702, respectively. The q(2)cv and r(2)ncv values for the selected CoMSIA model comprised four descriptors steric, electrostatic, hydrophobic and hydrogen bond donor fields were found to be 0.535 and 0.951, respectively. Obtained results showed that our generated model was statistically reliable. Furthermore, an external test set validates the reliability of the predicted model by calculating r(2)pred i.e.0.787 and 0.571 for CoMFA and CoMSIA model, respectively. 3D contour maps generated from CoMFA and CoMSIA models were utilized to determine the key structural features of ligands responsible for biological activities. The applied protocol will be helpful to design more potent and selective inhibitors of 5-LOX.

Purpose: Acetabular fractures are mainly caused by high energy trauma. Surgical fixation of these fractures requires extensive surgical exposure which increases the length of operation and blood loss as well. This may increase the risk of surgical site infection. Our aim is to evaluate the prevalence of surgical site infections and the risk factors associated with it so as to minimize its chances. Materials and Methods: A total of 261 patients who underwent acetabular fracture surgery were retrospectively reviewed. Patients were divided into 2 groups, with or without surgical site infection. Factors examined include patients` gender, age, body mass index (BMI), time between injury and surgery, operative time, estimated blood loss, number of packed red blood cell transfused, length of total intensive care unit (ICU) stay, fracture type, surgical approach, smoking status, patients` comorbids and associated injuries. Results: Fourteen patients (5.4%) developed surgical site infection. Out of 14 infections, 4 were superficial and 10 were deep. The factors that were found to be associated with surgical site infection following acetabular fracture fixation were prolonged operation time, increased BMI, prolonged ICU stay, larger amount of packed red blood cell transfused and associated genitourinary and abdominal trauma. Conclusion: In our study, we conclude that measures should be undertaken to attenuate the chances of surgical site infection in this major surgery by considering the risk factors significantly associated with it.

Purpose: Acetabular fractures are mainly caused by trauma and the incidence is rising in developing countries. Initially these fractures were managed conservatively, due to lack of specialized and dedicated acetabulum surgery centres. Our aim is to study the radiological and functional outcomes of surgical management of acetabular fractures in tertiary care hospital. Materials and Methods: Total 50 patients were enrolled. The patients with acetabular fractures were enrolled between the years 2012 to 2014. Patients were evaluated clinically with Harris hip score (HHS) and radiologically with Matta outcome grading. The factors examined include age, gender, fracture pattern, time between injury and surgery, initial displacement and quality of reduction on the final outcome. Results: There were 34 males and 16 females. Mean age was 44.20±11.65 years while mean duration of stay was 9.28±2.36 days. Duration of follow-up was 24 months. Most common mechanism of injury was motor vehicle accident (n=37, 74.0%). Open reduction and internal fixation of fractures were performed using reconstruction plates. Mean HHS at 24 months was 82.36±8.55. The clinical outcome was acceptable (excellent or good) in 35 (70.0%) cases and not acceptable (fair or poor) in 15 (30.0%) cases. The radiological outcome was anatomical in 39 (78.0%) cases, congruent in 5 (10.0%) cases, incongruent in 6 (12.0%) cases. Conclusion: Study results indicated that mechanism of injury, time between injury and surgery, initial degree of displacement and quality of reduction had significant effect on functional as well as radiological outcome.

Revisiting the origins of modern horses The domestication of horses was very important in the history of humankind. However, the ancestry of modern horses and the location and timing of their emergence remain unclear. Gaunitz et al. generated 42 ancient-horse genomes. Their source samples included the Botai archaeological site in Central Asia, considered to include the earliest domesticated horses. Unexpectedly, Botai horses were the ancestors not of modern domestic horses, but rather of modern Przewalski's horses. Thus, in contrast to current thinking on horse domestication, modern horses may have been domesticated in other, more Western, centers of origin. Science , this issue p. 111

Many mental health disorders emerge in late childhood and early adolescence and contribute to the burden of these disorders among young people and later in life. We systematically reviewed literature published up to December 2015 to identify systematic reviews on mental health interventions in adolescent population. A total of 38 systematic reviews were included. We classified the included reviews into the following categories for reporting the findings: school-based interventions (n = 12); community-based interventions (n = 6); digital platforms (n = 8); and individual-/family-based interventions (n = 12). Evidence from school-based interventions suggests that targeted group-based interventions and cognitive behavioral therapy are effective in reducing depressive symptoms (standard mean difference [SMD]: −.16; 95% confidence interval [CI]: −.26 to −.05) and anxiety (SMD: −.33; 95% CI: −.59 to −.06). School-based suicide prevention programs suggest that classroom-based didactic and experiential programs increase short-term knowledge of suicide (SMD: 1.51; 95% CI: .57–2.45) and knowledge of suicide prevention (SMD: .72; 95% CI: .36–1.07) with no evidence of an effect on suicide-related attitudes or behaviors. Community-based creative activities have some positive effect on behavioral changes, self-confidence, self-esteem, levels of knowledge, and physical activity. Evidence from digital platforms supports Internet-based prevention and treatment programs for anxiety and depression; however, more extensive and rigorous research is warranted to further establish the conditions. Among individual- and family-based interventions, interventions focusing on eating attitudes and behaviors show no impact on body mass index (SMD: −.10; 95% CI: −.45 to .25); Eating Attitude Test (SMD: .01; 95% CI: −.13 to .15); and bulimia (SMD: −.03; 95% CI: −.16 to .10). Exercise is found to be effective in improving self-esteem (SMD: .49; 95% CI: .16–.81) and reducing depression score (SMD: −.66; 95% CI: −1.25 to −.08) with no impact on anxiety scores. Cognitive behavioral therapy compared to waitlist is effective in reducing remission (odds ratio: 7.85; 95% CI: 5.31–11.6). Psychological therapy when compared to antidepressants have comparable effect on remission, dropouts, and depression symptoms. The studies evaluating mental health interventions among adolescents were reported to be very heterogeneous, statistically, in their populations, interventions, and outcomes; hence, meta-analysis could not be conducted in most of the included reviews. Future trials should also focus on standardized interventions and outcomes for synthesizing the exiting body of knowledge. There is a need to report differential effects for gender, age groups, socioeconomic status, and geographic settings since the impact of mental health interventions might vary according to various contextual factors.