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Introduction: There is dearth of information regarding the status of patient safety culture in Bhutanese healthcare system. The aim of the study was to assess the baseline patient safety culture among the healthcare professionals working in different levels of hospitals in Bhutan. Methods: A cross-sectional study was conducted using the Hospital Survey on Patient Safety, version 2 (HSOPS2) questionnaire in 2021 in six District Hospitals (DHs), two Regional Referral Hospitals (RRHs), and one National Referral Hospital (NRH) in Bhutan. A total of 782 healthcare professionals were recruited into the study. EpiData version 3.0 and Statistical Package for Social Science (SPSS) version 28.0 were used to process data and conduct the statistical analysis on survey data including descriptive statistics and validity and reliability of survey. The internal consistency reliability of each composite measure was assessed by calculating Cronbach’s alpha score. Results: The overall level of patient safety culture was 61.28% (95% CI: 113.26, 115.27) and the percentage scores for the ten patient safety dimensions ranged from 45.13% to 82.65%. The dimension, “Teamwork within the hospital units” had the highest positive score while the dimensions, “Staffing and work pace” and “Reporting patient safety events” had the lowest positive scores. Conclusions: The healthcare professionals working in hospitals in Bhutan had average patient safety culture. To improve patient safety culture, more emphasis should be given on human resource management, patient safety event reporting system, hospital management support for patient safety and quality improvement initiatives and creating an environment that promote just and learning culture.

Introduction: To address the suicide issue in the country, the Royal Government of Bhutan implemented a three year suicide prevention action plan from 1st July 2015 to 30th June 2018. As part of that action plan a national suicide registry was established under the Ministry of Health in January 2016 to collect comprehensive national data on suicide. The purpose of this study is to generate national information on suicide by analysing the suicide cases investigated and reported to suicide registry by the Forensic Department during the first two and half years. Methods: The study is a descriptive, retrospective and quantitative analysis of the suicide cases investigated by the Forensic Department from 1st January 2016 to 30th June 2018. The variables included the characteristics of the suicide victims. Result: Majority of the victims were young adults with no or low education and were either unemployed or employed with less income. 56.7% of the victims were women. Majority of them did not have physical illness or disability. About 45% had some form of mental health issues. Majority of them experienced some form of acute stressful event prior to committing suicide. Conclusion: Improved socioeconomic conditions through gainful employment, easily accessible mental health services and social support networks as well as population with good social and emotional skills will contribute to prevention of suicide in the country.

• Average bite mass was greater when pasture allowance was greater. • Bite mass was greatest in the first hour of grazing and then declined. • No difference in bite mass was found when cows grazed low and medium pasture mass. Dry matter intake (DMI) of herbage is a product of bite rate and bite mass and is a determinant of the performance of grazing ruminants. This research tested the effect of herbage allowance and herbage mass on average bite mass of individual dairy cows grazing perennial ryegrass herbage (Lolium perenne L.). Two experiments were conducted, one in each of winter (Experiment 1) and spring (Experiment 2). In each experiment, 24 Holstein-Friesian dairy cows grazed individual perennial ryegrass plots over 10 d. In each experiment cows grazed one of six treatments: low or medium herbage mass (1900 or 2200 kg DM.ha−1 in Experiment 1 and 2200 or 3000 kg DM.ha−1 in Experiment 2) combined with either low, medium or high herbage allowance (15, 25 or 40 kg DM.cow−1.d−1 in Experiment 1 and 20, 30 or 40 kg DM.cow−1.d-1 in Experiment 2). Grazing behaviour was measured with jaw movement sensors and DMI was determined by herbage disappearance measured with a rising plate meter daily, and at hourly intervals during the first 4 h of grazing after the morning milking. Average bite mass (g DM.bite−1) per day and per hour was determined as the mass of herbage that had disappeared in each period (g.d−1 or g. h−1) divided by number of prehension bites in that period. The combined data from two experiments was analysed by Linear Mixed Model and it was found there was no effect of herbage mass (P = 0.686) on bite mass per day. However, cows offered high herbage allowance had greater (P < 0.001) bite mass per day (0.62 g DM.bite-1) than cows offered the lowest herbage allowance (0.38 g DM.bite-1) across both experiments. The effect of herbage allowance was similar across both herbage masses. Bite mass per hour was the highest (P < 0.001) in the first hour of grazing in both experiments with average bite mass per hour across two experiments in the first hour of grazing (0.69 g DM.bite−1) greater than in the second (0.40 g DM.bite−1), third (0.35 g DM.bite−1) and fourth (0.32 g DM.bite−1) hours of grazing. We conclude that herbage allowance is a significant factor in determining bite mass and should be included in models aimed at predicting bite mass and hence daily herbage intake of grazing dairy cows. [ABSTRACT FROM AUTHOR]

Hippophae gyantsensis is a dioecious plant endemic to the Qinghai-Tibet Plateau and is significant for ecological restoration and sand stabilization. Its fruit is rich in bioactive compounds that offer economic potential. However, the inability to distinguish sexes before flowering and prolonged maturation hinder breeding and cultivation. We performed whole-genome resequencing on male and female plants, identified large insertion/deletion (InDel) variants, and developed two sex-specific primers (Higy&#95;04 and Higy&#95;06). These primers enable rapid, accurate PCR-based sex identification. All sex-specific sites were located on chromosome 2, suggesting its potential role as the sex chromosome. Additionally, we found a 1:1 sex ratio among offspring from the same mother plant, consistent with Mendelian inheritance, indicating that sex segregation is mainly genetically controlled. This work lays the foundation for developing molecular markers applicable across the entire genus Hippophae and contributes to understanding sex chromosome formation and adaptive evolution within the genus., Competing Interests: Declarations. Ethics approval and consent to participate: The research sample in this study is H. gyantsensis, which is not a protected plant species in China. All plant materials were collected and used with proper permissions and in compliance with relevant institutional, national, and international guidelines and legislation. Consent for publication: Not applicable. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The incidence of gallbladder cholesterol stones (GCS) increases rapidly among people living in high-altitude hypoxic environments compared to those in normoxic areas. Upregulation of hepatic hypoxia inducible factor 1α (Hif-1α) plays a key role in the formation of GCS. High plasma trimethylamine-N-oxide (TMAO) levels are positively correlated with the occurrence of GCS. We hypothesized that HIF-1α may upregulate TMAO levels by promoting the transcription of flavin-containing monooxygenase 3 (Fmo3), which eventually leads to GCS formation. Our study shows that in women, high plasma total cholesterol and apolipoprotein B were positively correlated with cholecystolithiasis and hypoxia. Hif-1α binds to the Fmo3 promoter and promotes Fmo3 expression. Hypoxia and lithogenic diet induce the expression of Hif-1α, Fmo3, TMAO and cholesterol tube transporters in the livers of mice, disturb the proportion of bile and plasma components, and induce the formation of GCS. In cell experiments, silencing Hif-1α downregulates the expression of Fmo3, TMAO and cholesterol tube transporters. In a mouse model of hypoxic cholecystolithiasis, silencing Hif-1α downregulates the expression of related genes, restores the proportion of bile and plasma lipid components, and reduces the formation of GCS. Our study shows that Hif-1α binds to the promoter region of Fmo3 and promotes Fmo3 transcription. Thus, it mediates the transcriptional activation of the TMA/Fmo3/TMAO pathway, upregulates the expression of ATP-binding cassettes (Abc) g5 and g8, and participates in the regulation of the occurrence of GCS in the plateau region., Competing Interests: Declaration of competing interest All authors have read the journal's policy on disclosure of potential conflicts of interest and have none to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The positive effects of meditation on human wellbeing are indisputable, ranging from emotion regulation improvement to stress reduction and present-moment awareness enhancement. Changes in brain activity regulate and support these phenomena. However, the heterogeneity of meditation practices and their cultural background, as well as their poor categorization limit the generalization of results to all types of meditation. Here, we took advantage of a collaboration with the very singular and precious community of the Monks and Geshes of the Tibetan University of Sera-Jey in India to study the neural correlates of the two main types of meditation recognized in Tibetan Buddhism, namely concentrative and analytical meditation. Twenty-three meditators with different levels of expertise underwent to an ecological (i.e., within the monastery) EEG acquisition consisting of an analytical and/or concentrative meditation session at "their best," and with the only constraint of performing a 5-min-long baseline at the beginning of the session. Time-varying power-spectral-density estimates of each session were compared against the baseline (i.e., within session) and between conditions (i.e., analytical vs. concentrative). Our results showed that concentrative meditation elicited more numerous and marked changes in the EEG power compared to analytical meditation, and mainly in the form of an increase in the theta, alpha and beta frequency ranges. Moreover, the full immersion in the Monastery life allowed to share the results and discuss their interpretation with the best scholars of the Monastic University, ensuring the identification of the most expert meditators, as well as to highlight better the differences between the different types of meditation practiced by each of them., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Neri, Callara, Vanello, Menicucci, Zaccaro, Piarulli, Laurino, Norbu, Kechok, Sherab and Gemignani.)

Recent studies have suggested that dogs were domesticated during the Last Glacial Maximum (LGM) in Siberia, which contrasts with previous proposed domestication centers (e.g. Europe, the Middle East, and East Asia). Ancient DNA provides a powerful resource for the study of mammalian evolution and has been widely used to understand the genetic history of domestic animals. To understand the maternal genetic history of East Asian dogs, we have made a complete mitogenome dataset of 120 East Asian canids from 38 archaeological sites, including 102 newly sequenced from 12.9 to 1 ka BP (1,000 years before present). The majority (112/119, 94.12%) belonged to haplogroup A, and half of these (55/112, 49.11%) belonged to sub-haplogroup A1b. Most existing mitochondrial haplogroups were present in ancient East Asian dogs. However, mitochondrial lineages in ancient northern dogs (northeastern Eurasia and northern East Asia) were deeper and older than those in southern East Asian dogs. Results suggests that East Asian dogs originated from northeastern Eurasian populations after the LGM, dispersing in two possible directions after domestication. Western Eurasian (Europe and the Middle East) dog maternal ancestries genetically influenced East Asian dogs from approximately 4 ka BP, dramatically increasing after 3 ka BP, and afterwards largely replaced most primary maternal lineages in northern East Asia. Additionally, at least three major mitogenome sub-haplogroups of haplogroup A (A1a, A1b, and A3) reveal at least two major dispersal waves onto the Qinghai-Tibet Plateau in ancient times, indicating eastern (A1b and A3) and western (A1a) Eurasian origins., Competing Interests: Conflict of Interest The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Purpose: To perform a descriptive epidemiologic analysis of National Basketball Association (NBA) injuries from 2016 to 2021, to evaluate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019, or COVID-19) on injury patterns and performance statistics, and to determine the effect of infection with SARS-CoV-2 on individual performance statistics., Methods: Injury epidemiology in the NBA from the 2016 to 2021 seasons was collected using a comprehensive online search. Injuries and time missed were categorized by injury location and type. Player positions and timing of injury were recorded. Performance statistics were collected including traditional game statistics and Second Spectrum (speed, distance) statistics. Comparisons were made over seasons and comparing the pre-COVID-19 pandemic seasons to the pandemic era seasons. Players diagnosed with COVID-19 were analyzed for changes in performance in the short or long term., Results: Of the 3,040 injuries captured, 1,880 (61.84%) were in the lower extremity. Guards (77.44%) and forwards (75.88%) had a greater proportion of soft-tissue injuries ( P < .001) than centers. Guards had the highest proportion of groin (3.27%, P  = .001) and hamstring (6.21%, P < .001) injuries. Despite minor differences on a per-season basis, there were no differences in injury patterns identified between pre-COVID-19 and COVID-19 eras. Of players diagnosed with COVID-19 during the NBA Bubble, there were no detriments in short- or long-term performance identified, including traditional game statistics and speed and distance traveled., Conclusions: In the NBA seasons from 2016 to 2021, most injuries were to the lower extremity. The SARS-CoV-2 pandemic did not substantially impact injury patterns in the NBA, including locations of injury and type of injury (bony or soft tissue). Furthermore, infection with SARS-CoV-2 does not appear to have a significant impact on performance in basketball-specific or speed and distance measures., Level of Evidence: Level IV, prognostic case series., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: N.K.P. reports consultant for OrthoPediatrics and educational support from Evolution Surgical, Inc. All other authors (Sachin A., A.R.G., N.C., N.T., A.P.G., J.C.M., Sameer A.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (© 2023 The Authors.)

The settlement of the Tibetan Plateau epitomizes human adaptation to a high-altitude environment that poses great challenges to human activity. Here, we reconstruct a 4000-year maternal genetic history of Tibetans using 128 ancient mitochondrial genome data from 37 sites in Tibet. The phylogeny of haplotypes M9a1a, M9a1b, D4g2, G2a'c, and D4i show that ancient Tibetans share the most recent common ancestor with ancient Middle and Upper Yellow River populations around the Early and Middle Holocene. In addition, the connections between Tibetans and Northeastern Asians vary over the past 4000 years, with a stronger matrilineal connection between the two during 4000 BP-3000 BP, and a weakened connection after 3000 BP, that are coincident with climate change, followed by a reinforced connection after the Tubo period (1400 BP-1100 BP). Besides, an over 4000-year matrilineal continuity is observed in some of the maternal lineages. We also find the maternal genetic structure of ancient Tibetans is correlated to the geography and interactions between ancient Tibetans and ancient Nepal and Pakistan populations. Overall, the maternal genetic history of Tibetans can be characterized as a long-term matrilineal continuity with frequent internal and external population interactions that are dynamically shaped by geography, climate changes, as well as historical events., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Using genome-wide data of 89 ancient individuals dated to 5100 to 100 years before the present (B.P.) from 29 sites across the Tibetan Plateau, we found plateau-specific ancestry across plateau populations, with substantial genetic structure indicating high differentiation before 2500 B.P. Northeastern plateau populations rapidly showed admixture associated with millet farmers by 4700 B.P. in the Gonghe Basin. High genetic similarity on the southern and southwestern plateau showed population expansion along the Yarlung Tsangpo River since 3400 years ago. Central and southeastern plateau populations revealed extensive genetic admixture within the plateau historically, with substantial ancestry related to that found in southern and southwestern plateau populations. Over the past ~700 years, substantial gene flow from lowland East Asia further shaped the genetic landscape of present-day plateau populations. The high-altitude adaptive EPAS1 allele was found in plateau populations as early as in a 5100-year-old individual and showed a sharp increase over the past 2800 years.

Thousand-year-old Buddhist traditions have developed a wide range of methods for the subjective exploration of consciousness through meditation. Combining their subjective research with the possibilities of modern neuroscience can help us better understand the physiological mechanisms of consciousness. Therefore, we have been guided by specifically Buddhist explanations when studying the physiological mechanisms of altered states of consciousness during Buddhist meditations. In Buddhism, meditations are generally divided into two large categories: (1) one-pointed concentration and (2) analytical meditation. Maintaining both one-pointed concentration and analytical meditation on 'bodhicitta' ("the thought of awakening") and 'emptiness' is a necessary condition for transitioning into tantric practices. Tantric practices involve sophisticated visualizations of Buddhist deities, the 'energy structure' of the human body, and the visualization of the stage-by-stage process of dying accompanied with the dissolution of body elements. According to Buddhism, these meditations are characterized by the gradual withdrawal from "gross levels" of consciousness associated with the five senses. From a psychophysiological perspective, this withdrawal of sensory consciousness can be considered as the decrease of sensory stimuli recognition and attentional disengagement from the external world. We concentrated on how considered meditations affect sensory and cognitive processing of external stimuli. Auditory event-related potentials (ERPs) in the passive oddball paradigm were studied both during meditations and in a controlled state of relaxed wakefulness. It was shown with a group of 115 Buddhist monks that during meditation, mismatch negativity amplitudes, amplitudes of N1 and P2 components of ERPs to deviant stimuli, and the amplitudes of the P3a component to novel stimuli all decrease. These outcomes suggest that the considered Buddhist meditations, compared to the control state of relaxed wakefulness, are accompanied by a decrease in physiological processes responsible for maintaining attention on the outside world and recognizing changes in the stream of sensory stimuli., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study attempted to discuss the historical context and current practice of forensic medicine in South Asia. Comparisons within and between countries in South Asia, and between South Asia and the developed countries (represented by Japan and the USA) have been made to provide an insight into their distinct practice of forensic medicine. Though the formal establishment of forensic medicine in South Asia commenced at a comparable period to the developed countries, their pace of development has been considerably slow. Moreover, their ways of practice as well have evolved differently. In effect, South Asian countries follow an 'integrated service' system, whilst Japan and the USA practice 'divided service' systems to provide forensic medical services. Similarly, regarding the death investigations, most South Asian countries follow a Police-led death investigation system, whereas Japan and the USA follow a hybrid model and the Medical examiner's system of death investigation, respectively. Indeed, forensic medicine in South Asia is undeniably underdeveloped. In this paper, by highlighting the issues and challenges confronted in South Asia, key actions for prompt redressal are discussed to improve the standard of forensic medical services in South Asia., Competing Interests: The authors declare no conflict of interest., (©2022 Tottori University Medical Press.)

Background: Physician well-being is critical for optimal care, but rates of psychological distress among surgical trainees are rising. Although numerous efforts have been made, the perceived efficacy of well-being interventions is not well understood., Study Design: This qualitative thematic study included online questionnaires to Program Directors (PDs) and residents at 16 ACGME-accredited General Surgery residency programs. PDs reported active well-being interventions for surgical residents or those under consideration at their institutions. Residents shared perspectives of available well-being interventions through open-ended responses. Conventional content analysis was used to analyze responses., Results: Fifteen PDs, or their proxies (94% response rate), responded. Responses revealed that a majority of available well-being interventions are focused on changing the individual experience rather than the underlying workplace. PD decision-making around well-being interventions is often not based on objective data. Three hundred residents (34% response rate) responded. Of available interventions, those that increase control (eg advanced and flexible scheduling), increase support (eg mentorship), and decrease demand (eg work hour limits) were consistently identified as beneficial, but interventions perceived to increase demand (eg held during unprotected time) were consistently identified as not beneficial. Group social activities, cognitive skills training, and well-being committees were variably seen as beneficial (increasing support) or not (increasing demand)., Conclusions: Our findings underscore the prevalence of individual-based well-being interventions and the paucity of system-level changes. This may explain, in part, the persistence of distress among residents despite abundant effort, highlighting the imperative for system-level transformation., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Brain glioma is the most common primary tumour of the central nervous system. Complete surgical removal of the brain glioma is virtually impossible. Chemotherapy is still an important treatment for brain glioma. However, blood-brain barrier (BBB) and vasculogenic mimicry (VM) channels remain two hindrances in regular treatments. Herein, we developed a novel nanoscaled dual targeting daunorubicin plus rofecoxib liposomes which could transport across the BBB, and eliminate brain glioma cells along with the VM channels. The liposomes were modified with two functional materials, and showed round in shape with a diameter about 120 nm. Evaluations were performed on human brain glioma U87MG cells in vitro and on intracranial brain glioma-bearing nude mice. The dual targeting liposomes demonstrated a long circulatory effect in the blood system, were able to transport across the BBB, and were accumulated into the brain. The results indicated that the dual targeting daunorubicin plus rofecoxib liposomes could inhibit the brain glioma VM channels and exhibited a significant efficacy in the treatment of intracranial glioma-bearing nude mice. The mechanisms are related to down regulations MMP-2, MMP-9, FAK and HIF-α. Hence, the established dual targeting liposomes could be a potential formulation to treat the brain glioma along with eliminating VM channels.

A 3-y-3-mo old male child presented with massive hypertrophy and bluish-purple discoloration of the left upper limb and adjacent chest wall of 3 mo duration. There was no h/o fever, weight loss, painful large joint swelling, or any bleeding manifestations. He had spindle like nonprogressive, painless swelling of all fingers of the left hand since infancy. The child was moribund with microangiopathic hemolytic anemia, thrombocytopenia, and consumptive coagulopathy without sepsis. He received multiple transfusions of fresh frozen plasma (FFP), platelets, and packed RBC. Paradoxical worsening of symptoms with platelet transfusions and radiological evidences led to the diagnosis of a very rare congenital multifocal vascular tumor, kaposiform hemangioendothelioma (KHE) with Kasabach-Merritt phenomenon (KMP). The index case of KHE was multifocal with cutaneous lesions, osteolytic bony lesions of all phalanx and metacarpals of the left hand, and intrathoracic extension. It was successfully managed with a combination of steroid, vincristine and sirolimus., (© 2021. Dr. K C Chaudhuri Foundation.)

Modern feces samples of the endangered red panda (Ailurus fulgens) were examined using multiproxy analysis to characterize the dietary patterns in their natural habitat in India. An abundance of Bambusoideae phytoliths and leaves (macrobotanical remains) provide direct evidence of their primary dietary plants. In contrast, Bambusoideae pollen is sporadic or absent in the pollen assemblages. An abundance of Lepisorus spores and its leaves along with broadleaved taxa, Betula, Engelhardtia, and Quercus are indicative of other important food sources. Average δ 13 C values (- 29.6‰) of the red panda feces indicate typical C 3 type of plants as the primary food source, while the, δ 15 N values vary in narrow range (3.3-5.1‰) but conspicuously reveal a seasonal difference in values most likely due to differing metabolic activities in summer and winter. The multiproxy data can provide a baseline for the reconstruction of the palaeodietary and palaeoecology of extinct herbivores at both regional and global scales., (© 2021. The Author(s).)

Bats represent the largest dietary radiation in a single mammalian order, and have become an emerging model group for studying dietary evolution. Taste receptor genes have proven to be molecular signatures of dietary diversification in bats. For example, all 3 extant species of vampire bats have lost many bitter taste receptor genes (Tas2rs) in association with their dietary shift from insectivory to sanguivory. Indeed, only 8 full-length Tas2rs were identified from the high-quality genome of the common vampire bat (Desmodus rotundus). However, it is presently unknown whether these bitter receptors are functional, since the sense of taste is less important in vampire bats, which have an extremely narrow diet and rely on other senses for acquiring food. Here, we applied a molecular evolutionary analysis of Tas2rs in the common vampire bat compared with non-vampire bats. Furthermore, we provided the first attempt to deorphanize all bitter receptors of the vampire bat using a cell-based assay. We found that all Tas2r genes in the vampire bat have a level of selective pressure similar to that in non-vampire bats, suggesting that this species must have retained some bitter taste functions. We demonstrated that 5 of the 8 bitter receptors in the vampire bat can be activated by some bitter compounds, and observed that the vampire bat generally can not detect naturally occurring bitter compounds examined in this study. Our study demonstrates functional retention of bitter taste in vampire bats as suggested by cell-based functional assays, calling for an in-depth study of extra-oral functions of bitter taste receptors., (© 2020 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Lung cancer is a kind of malignant tumour characterized as uncontrolled cell growth in lung. These malignant cell growth can spread beyond the lung by process of metastasis into other tissues or parts of the body. In this study, we developed dequalinium (DQA) modified paclitaxel plus ligustrazine micelles to destroy vasculogenic mimicry (VM) channels and inhibit tumour metastasis. In vitro assays showed that the targeting micelles with centralized particle size distribution showed not only vigoroso cytotoxicity on A549 cells but also strong inhibition on VM channels and tumour metastasis. Mechanism studies indicated that the DQA modified paclitaxel plus ligustrazine micelles could down-regulate the expressions of VEGF, MMP2, TGF-β1 and E-cadherin in A549 cells. In vivo assays indicated that the targeting drug-loaded micelles could enhance the accumulation of chemotherapeutic drugs at tumour sites and exhibit strong tumour inhibitory activity with negligible toxicity. Hence, the DQA modified paclitaxel plus ligustrazine micelles developed in this study may provide a potential strategy for treatment of NSCLC.

Analytical meditation and monastic debate are contemplative practices engaged in by Tibetan Buddhist monastics that have up to now been largely unexplored in Western contemplative science. The highly physical form of contemplative debating plays an important role in the monastic curriculum. Based on discussions and recorded interviews Tibetan monastic teachers and senior students at Sera Jey Monastic University and preliminary experiments, we outline an initial theory that elucidates the psychological mechanisms underlying this practice. We then make predictions about the potential effects of this form of debating on cognition and emotion. On the basis of initial observations, we propose that successful debating requires skills that include reasoning and critical thinking, attentional focus, working memory, emotion regulation, confidence in your own reasoning skills, and social connectedness. It is therefore likely that the many cumulative hours of debate practice over 20+ years of monastic training helps to cultivate these very skills. Scientific research is needed to examine these hypotheses and determine the role that monastic debate may play in terms of both psychological wellbeing and educational achievement., (© 2019 Elsevier B.V. All rights reserved.)

Many large carnivores occupy a wide geographic distribution, and face threats from habitat loss and fragmentation, poaching, prey depletion, and human wildlife-conflicts. Conservation requires robust techniques for estimating population densities and trends, but the elusive nature and low densities of many large carnivores make them difficult to detect. Spatial capture-recapture (SCR) models provide a means for handling imperfect detectability, while linking population estimates to individual movement patterns to provide more accurate estimates than standard approaches. Within this framework, we investigate the effect of different sample interval lengths on density estimates, using simulations and a common leopard (Panthera pardus) model system. We apply Bayesian SCR methods to 89 simulated datasets and camera-trapping data from 22 leopards captured 82 times during winter 2010-2011 in Royal Manas National Park, Bhutan. We show that sample interval length from daily, weekly, monthly or quarterly periods did not appreciably affect median abundance or density, but did influence precision. We observed the largest gains in precision when moving from quarterly to shorter intervals. We therefore recommend daily sampling intervals for monitoring rare or elusive species where practicable, but note that monthly or quarterly sample periods can have similar informative value. We further develop a novel application of Bayes factors to select models where multiple ecological factors are integrated into density estimation. Our simulations demonstrate that these methods can help identify the "true" explanatory mechanisms underlying the data. Using this method, we found strong evidence for sex-specific movement distributions in leopards, suggesting that sexual patterns of space-use influence density. This model estimated a density of 10.0 leopards/100 km2 (95% credibility interval: 6.25-15.93), comparable to contemporary estimates in Asia. These SCR methods provide a guide to monitor and observe the effect of management interventions on leopards and other species of conservation interest.

Background: Altitudinal migration systems are poorly understood. Recent advances in animal telemetry which enables tracking of migrants across their annual cycles will help illustrate unknown migration patterns and test existing hypotheses. Using telemetry, we show the existence of a complex partial altitudinal migration system in the Himalayas and discuss our findings to help better understand partial and altitudinal migration., Methodology/principal Findings: We used GPS/accelerometer tags to monitor the migration of Satyr tragopan (Tragopan satyra) in the Bhutan Himalayas. We tagged 38 birds from 2009 - 2011 and found that tragopans are partially migratory. Fall migration lasted from the 3(rd) week of September till the 3(rd) week of November with migrants traveling distances ranging from 1.25 km to 13.5 km over 1 to 32 days. Snowfall did not influence the onset of migration. Return migration started by the 1(st) week of March and lasted until the 1(st) week of April. Individuals returned within 4 to 10 days and displayed site fidelity. One bird switched from being a migrant to a non-migrant. Tragopans displayed three main migration patterns: 1) crossing multiple mountains; 2) descending/ascending longitudinally; 3) moving higher up in winter and lower down in summer. More females migrated than males; but, within males, body size was not a factor for predicting migrants., Conclusions/significance: Our observations of migrants traversing over multiple mountain ridges and even of others climbing to higher elevations is novel. We support the need for existing hypotheses to consider how best to explain inter- as well as intra-sexual differences. Most importantly, having shown that the patterns of an altitudinal migration system are complex and not a simple up and down slope movement, we hope our findings will influence the way altitudinal migrations are perceived and thereby contribute to a better understanding of how species may respond to climate change.

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.