Miracle-dz/UniFAR-FTUs huggingface dataset:
Time Flies—Age Grading of Adult Flies for the Estimation of the Post-Mortem Interval

The estimation of the minimum time since death is one of the main applications of forensic entomology. This can be done by calculating the age of the immature stage of necrophagous flies developing on the corpse, which is confined to approximately 2–4 weeks, depending on temperature and species of the first colonizing wave of flies. Adding the age of the adult flies developed on the dead body could extend this time frame up to several weeks when the body is in a building or closed premise. However, the techniques for accurately estimating the age of adult flies are still in their beginning stages or not sufficiently validated. Here we review the current state of the art of analysing the aging of flies by evaluating the ovarian development, the amount of pteridine in the eyes, the degree of wing damage, the modification of their cuticular hydrocarbon patterns, and the increasing number of growth layers in the cuticula. New approaches, including the use of age specific molecular profiles based on the levels of gene and protein expression and the application of near infrared spectroscopy, are introduced, and the forensic relevance of these methods is discussed.
DNA-Binding Anticancer Drugs: One Target, Two Actions

Amsacrine, an anticancer drug first synthesised in 1970 by Professor Cain and colleagues, showed excellent preclinical activity and underwent clinical trial in 1978 under the auspices of the US National Cancer Institute, showing activity against acute lymphoblastic leukaemia. In 1984, the enzyme DNA topoisomerase II was identified as a molecular target for amsacrine, acting to poison this enzyme and to induce DNA double-strand breaks. One of the main challenges in the 1980s was to determine whether amsacrine analogues could be developed with activity against solid tumours. A multidisciplinary team was assembled in Auckland, and Professor Denny played a leading role in this approach. Among a large number of drugs developed in the programme, N-[2-(dimethylamino)-ethyl]-acridine-4-carboxamide (DACA), first synthesised by Professor Denny, showed excellent activity against a mouse lung adenocarcinoma. It underwent clinical trial, but dose escalation was prevented by ion channel toxicity. Subsequent work led to the DACA derivative SN 28049, which had increased potency and reduced ion channel toxicity. Mode of action studies suggested that both amsacrine and DACA target the enzyme DNA topoisomerase II but with a different balance of cellular consequences. As primarily a topoisomerase II poison, amsacrine acts to turn the enzyme into a DNA-damaging agent. As primarily topoisomerase II catalytic inhibitors, DACA and SN 28049 act to inhibit the segregation of daughter chromatids during anaphase. The balance between these two actions, one cell cycle phase specific and the other nonspecific, together with pharmacokinetic, cytokinetic and immunogenic considerations, provides links between the actions of acridine derivatives and anthracyclines such as doxorubicin. They also provide insights into the action of cytotoxic DNA-binding drugs.
Childhood maltreatment, personality vulnerability profiles, and borderline personality disorder symptoms in adolescents

Abstract Adverse childhood experiences are significant risk factors in the development of adolescent borderline personality disorder symptoms (BPDs). Theorists have posited that two personality vulnerabilities factors, self-criticism and dependency, may inform our understanding of this relationship. However, no research has examined the associations between early negative experiences, personality vulnerabilities, and adolescent BPDs. The current study aimed to identify profiles of dependency and self-criticism to examine the associations of these profiles with cumulative forms of childhood maltreatment (CM) and BPDs as well as to explore the mediating and moderating role of vulnerable personality profiles in the relationship between cumulative CM and BPDs. Two hundred and forty-one nonclinical and clinical adolescents participated in the study (Mage = 16.37, SD = 1.84). The findings indicated three different profiles: average dependent profile, dependent and self-critical profile, and self-critical profile. Individuals in the average dependent profile presented lower levels of CM and BPDs. Mediation analyses showed that relative to the average dependent profile, a higher cumulative CM history predicted a higher probability of belonging in the dependent and self-critical profile or the self-critical profile and, in turn, this was associated with higher levels of BPDs. No moderating effects of profiles of dependency and self-criticism were found.
Milk Production, Body Weight, Body Condition Score, Activity, and Rumination of Organic Dairy Cattle Grazing Two Different Pasture Systems Incorporating Cool- and Warm-Season Forages

Simple Summary Organic dairy cows were used to evaluate the effect of two pasture production systems on milk, fat, and protein production, somatic cell score, milk urea nitrogen, body weight, body condition score, and activity and rumination. Milk production increased when cows grazed sorghum-sudangrass compared to when they grazed perennial grasses and legumes. Warm-season annual grasses may be incorporated into grazing systems for organic dairy cattle while maintaining milk production and components. Abstract Organic dairy cows were used to evaluate the effect of two organic pasture production systems (temperate grass species and warm-season annual grasses and cool-season annuals compared with temperate grasses only) across two grazing seasons (May to October of 2014 and 2015) on milk production, milk components (fat, protein, milk urea nitrogen (MUN), somatic cell score (SCS)), body weight, body condition score (BCS), and activity and rumination (min/day). Cows were assigned to two pasture systems across the grazing season at an organic research dairy in Morris, Minnesota. Pasture System 1 was cool-season perennials (CSP) and Pasture System 2 was a combination of System 1 and warm-season grasses and cool-season annuals. System 1 and System 2 cows had similar milk production (14.7 and 14.8 kg d−1), fat percentage (3.92% vs. 3.80%), protein percentage (3.21% vs. 3.17%), MUN (12.5 and 11.5 mg dL−1), and SCS (4.05 and 4.07), respectively. Cows in System 1 had greater daily rumination (530 min/day) compared to cows in System 2 (470 min/day). In summary, warm-season annual grasses may be incorporated into grazing systems for pastured dairy cattle.
Dissecting dynamics and differences of selective pressures in the evolution of human pigmentation

ABSTRACT Human pigmentation is a highly diverse and complex trait among populations and has drawn particular attention from both academic and non-academic investigators for thousands of years. Previous studies detected selection signals in several human pigmentation genes, but few studies have integrated contribution from multiple genes to the evolution of human pigmentation. Moreover, none has quantified selective pressures on human pigmentation over epochs and between populations. Here, we dissect dynamics and differences of selective pressures during different periods and between distinct populations with new approaches. We use genotype data of 19 genes associated with human pigmentation from 17 publicly available datasets and obtain data for 2346 individuals of six representative population groups from across the world. Our results quantify the strength of natural selection on light pigmentation not only in modern Europeans (0.0259/generation) but also in proto-Eurasians (0.00650/generation). Our results also suggest that several derived alleles associated with human dark pigmentation may be under positive directional selection in some African populations. Our study provides the first attempt to quantitatively investigate the dynamics of selective pressures during different time periods in the evolution of human pigmentation. This article has an associated First Person interview with the first author of the article. Summary: This study developed a novel approach to estimate selection strength over time and applied it on the evolution of human pigmentation.
Mixed micelles for enhanced oral bioavailability and hypolipidemic effect of liquiritin: preparation, in vitro and in vivo evaluation

Abstract Objectives Liquiritin, as one of the main flavonoids in Glycyrrhiza, exhibits extensive pharmacological effects, such as the anti-oxidant, anti-inflammatory, anti-tumor and so on. Herein, the aqueous solubility and oral bioavailability of liquiritin was purposely enhanced via the preparation of the mixed micelles. Methods The liquiritin-loaded micelles (LLM) were fabricated via thin-film dispersion method. The optimal LLM formulation was evaluated through physical properties including particle size (PS), encapsulation efficiency (EE) and drug loading (DL). In vitro accumulate release as well as in vivo pharmacokinetics were also evaluated. Moreover, the hypolipidemic activity of LLM was observed in the hyperlipidemia mice model. Results The LLM exhibited a homogenous spherical shape with small mean PS, good stability and high encapsulation efficiency. The accumulate release rates in vitro of the LLM were obviously higher than free liquiritin. The oral bioavailability of the formulation was heightened by 3.98 times in comparison with the free liquiritin. More importantly, LLM increased the hypolipidemic and effect of alleviating lipid metabolism disorder in hepatocytes of liquiritin in hyperlipidemia mice model. Conclusions Collectively, the improved solubility of liquiritin in water coupled with its enhanced oral bioavailability and concomitant hypolipidemic activity could be attributed to the incorporation of the drug into the mixed micelles.
Cell-phone traces reveal infection-associated behavioral change

Significance Infectious disease control critically depends on surveillance and predictive modeling of outbreaks. We argue that routine mobile-phone use can provide a source of infectious disease information via the measurements of behavioral changes in call-detail records (CDRs) collected for billing. In anonymous CDR metadata linked with individual health information from the A(H1N1)pdm09 outbreak in Iceland, we observe that people moved significantly less and placed fewer, but longer, calls in the few days around diagnosis than normal. These results suggest that disease-transmission models should explicitly consider behavior changes during outbreaks and advance mobile-phone traces as a potential universal data source for such efforts. Epidemic preparedness depends on our ability to predict the trajectory of an epidemic and the human behavior that drives spread in the event of an outbreak. Changes to behavior during an outbreak limit the reliability of syndromic surveillance using large-scale data sources, such as online social media or search behavior, which could otherwise supplement healthcare-based outbreak-prediction methods. Here, we measure behavior change reflected in mobile-phone call-detail records (CDRs), a source of passively collected real-time behavioral information, using an anonymously linked dataset of cell-phone users and their date of influenza-like illness diagnosis during the 2009 H1N1v pandemic. We demonstrate that mobile-phone use during illness differs measurably from routine behavior: Diagnosed individuals exhibit less movement than normal (1.1 to 1.4 fewer unique tower locations; P<3.2×10−3), on average, in the 2 to 4 d around diagnosis and place fewer calls (2.3 to 3.3 fewer calls; P<5.6×10−4) while spending longer on the phone (41- to 66-s average increase; P<4.6×10−10) than usual on the day following diagnosis. The results suggest that anonymously linked CDRs and health data may be sufficiently granular to augment epidemic surveillance efforts and that infectious disease-modeling efforts lacking explicit behavior-change mechanisms need to be revisited.
Cow’s Milk Allergy or Gastroesophageal Reflux Disease—Can We Solve the Dilemma in Infants?

Cow’s milk allergy (CMA) and gastro-esophageal reflux disease (GERD) may manifest with similar symptoms in infants making the diagnosis challenging. While immediate reaction to cow’s milk protein indicate CMA, regurgitation, vomiting, crying, fussiness, poor appetite, sleep disturbances have been reported in both CMA and GERD and in other conditions such as functional gastrointestinal disorders, eosinophilic esophagitis, anatomic abnormalities, metabolic and neurological diseases. Gastrointestinal manifestations of CMA are often non-IgE mediated and clinical response to cow’s milk free diet is not a proof of immune system involvement. Neither for non-IgE CMA nor for GERD there is a specific symptom or diagnostic test. Oral food challenge, esophageal pH impedance and endoscopy are recommended investigations for a correct clinical classification but they are not always feasible in all infants. As a consequence of the diagnostic difficulty, both over- and under- diagnosis of CMA or GERD may occur. Quite frequently acid inhibitors are empirically started. The aim of this review is to critically update the current knowledge of both conditions during infancy. A practical stepwise approach is proposed to help health care providers to manage infants presenting with persistent regurgitation, vomiting, crying or distress and to solve the clinical dilemma between GERD or CMA.
Associations between intake of calcium, magnesium and phosphorus and risk of pancreatic cancer: a population-based, case–control study in Minnesota

Abstract Experimental studies suggest that abnormal levels of Ca, Mg and phosphorus are implicated in pancreatic carcinogenesis. We investigated the associations between intakes of these minerals and the risk of pancreatic cancer in a case-control study conducted in 1994–1998. Cases of pancreatic cancer (n 150) were recruited from all hospitals in the metropolitan area of the Twin Cities and Mayo Clinic, Minnesota. Controls (n 459) were randomly selected from the general population and frequency matched to cases by age, sex and race. All dietary variables were adjusted for energy intake using the residual method prior to data analysis. Logistic regression was performed to evaluate the associations between intake of three nutrients examined and the risk of pancreatic cancer. Total intake of Ca (936 v. 1026 mg/d) and dietary intake of Mg (315 v. 331 mg/d) and phosphorus (1350 v. 1402 mg/d) were significantly lower in cases than in controls. After adjustment for confounders, there were not significant associations of total and dietary intakes of Ca, Mg and phosphorus with the risk of pancreatic cancer. In addition, no significant interactions exist between intakes of these minerals and total fat on pancreatic cancer risk. In conclusion, the present study does not suggest that intakes of Ca, Mg and phosphorus were significantly associated with the risk of pancreatic cancer.
Pilot Study to Characterize Middle Cerebral Artery Dynamic Response to an Acute Bout of Moderate Intensity Exercise at 3‐ and 6‐Months Poststroke

Background The primary aim of this study was to characterize the middle cerebral artery blood velocity (MCAv) dynamic response to an acute bout of exercise in humans at 3‐ and 6‐months poststroke. As a secondary objective, we grouped individuals according to the MCAv dynamic response to the exercise bout as responder or nonresponder. We tested whether physical activity, aerobic fitness, and exercise mean arterial blood pressure differed between groups. Methods and Results Transcranial Doppler ultrasound measured MCAv during a 90‐second baseline followed by a 6‐minute moderate intensity exercise bout. Heart rate, mean arterial blood pressure, and end‐tidal CO2 were additional variables of interest. The MCAv dynamic response variables included the following: baseline, time delay, amplitude, and time constant. Linear mixed model revealed no significant differences in our selected outcomes between 3‐ and 6‐months poststroke. Individuals characterized as responders demonstrated a faster time delay, higher amplitude, and reported higher levels of physical activity and aerobic fitness when compared with the nonresponders. No between‐group differences were identified for baseline, time constant, or exercise mean arterial blood pressure. In the nonresponders, we observed an immediate rise in MCAv following exercise onset followed by an immediate decline to near baseline values, while the responders showed an exponential rise until steady state was reached. Conclusions The MCAv dynamic response profile has the potential to provide valuable information during an acute exercise bout following stroke. Individuals with a greater MCAv response to the exercise stimulus reported statin use and regular participation in exercise.
Binocular Suppression in the Macaque Lateral Geniculate Nucleus Reveals Early Competitive Interactions between the Eyes

Abstract The lateral geniculate nucleus (LGN) of the dorsal thalamus is the primary recipient of the two eyes’ outputs. Most LGN neurons are monocular in that they are activated by visual stimulation through only one (dominant) eye. However, there are both intrinsic connections and inputs from binocular structures to the LGN that could provide these neurons with signals originating from the other (non-dominant) eye. Indeed, previous work introducing luminance differences across the eyes or using a single-contrast stimulus showed binocular modulation for single unit activity in anesthetized macaques and multiunit activity in awake macaques. Here, we sought to determine the influence of contrast viewed by both the non-dominant and dominant eyes on LGN single-unit responses in awake macaques. To do this, we adjusted each eye’s signal strength by independently varying the contrast of stimuli presented to the two eyes. Specifically, we recorded LGN single unit spiking activity in two awake macaques while they viewed drifting gratings of varying contrast. We found that LGN neurons of all types [parvocellular (P), magnocellular (M), and koniocellular (K)] were significantly suppressed when stimuli were presented at low contrast to the dominant eye and at high contrast to the non-dominant eye. Further, the inputs of the two eyes showed antagonistic interaction, whereby the magnitude of binocular suppression diminished with high contrast in the dominant eye, or low contrast in the non-dominant eye. These results suggest that the LGN represents a site of precortical binocular processing involved in resolving discrepant contrast differences between the eyes.
Effect of pH and water‐soluble polymers on the aqueous solubility of nimesulide in the absence and presence of β‐cyclodextrin derivatives

The aqueous solubility of nimesulide in the absence and presence of β‐cyclodextrin (β‐CD) and its alkyl derivatives hydroxypropyl‐β‐CD and methyl‐β‐CD was studied. We also investigated the effect of water‐soluble polymers, hydroxypropylmethyl‐cellulose, sodium‐carboxymethyl‐cellulose, polyvinyl‐ pyrrolidone and polyethyleneglycol on the solubilization efficacy and complexation ability of cyclodextrins with nimesulide. The solubility of nimesulide in the absence and presence of cyclodextrins and polymers was studied using a phase solubility technique combined with a spectrophotometric method. The study was carried out at 25°C and pH values of 6.0 and 7.0. Conditions in terms of polymer concentration and polymer heating with and without sonication were optimized. Values of the solubility enhancement factor of nimesulide in the presence of each cyclodextrin and in the absence and presence of each polymer were determined and the formation constants, K, of the inclusion complexes formed calculated. β‐CDs increased the aqueous solubility of nimesulide in the following order: methyl‐β‐CD > β‐CD > hydroxypropyl‐β‐CD. Addition of hydroxypropylmethyl‐cellulose at a concentration of 0.1% (w/v) had the greatest influence on complexation of all three β‐CDs with nimesulide, while preheating of the polymer at 70°C under sonication resulted in an additional two‐fold increase in the aqueous solubility of the drug. Sodium‐ carboxymethyl‐cellulose, polyvinylpyrrolidone and polyethyleneglycol had minor effects on the aqueous solubility of nimesulide. Thus β‐CD, hydroxypropyl‐β‐CD and methyl‐β‐CD are proposed as good solubilizing agents for nimesulide in the presence and absence of hydroxypropylmethyl‐ cellulose in order to enhance its oral bioavailability.
Increased risk of subclinical atherosclerosis and metabolic syndrome in patients with vitiligo: a real association or a coincidence?

Inflammatory and autoimmune skin diseases such as vitiligo may be associated with systemic disorders, including endocrine and cardiovascular diseases, due to some similarities in the pathogenesis. It was aimed to evaluate metabolic syndrome and subclinical atherosclerosis in patients with vitiligo. Seventy patients with nonsegmental vitiligo and 70 age‐matched and gender‐matched healthy controls participated in the study. These participants were investigated for metabolic syndrome criteria. The mean intima‐media thickness of the common carotid artery (MIMT‐CCA) of the subjects was measured for assessment of subclinical atherosclerosis. Metabolic syndrome and subclinical atherosclerosis were significantly more frequent in vitiligo patients compared with the controls (P = .006 and P = .002, respectively). In addition, metabolic syndrome and subclinical atherosclerosis had positive, significant correlations with the severity and duration of vitiligo (P = .031 and r = .482; P < .01, respectively). Our study suggested that patients with vitiligo, especially those with more chronic and severe disease or concomitant metabolic syndrome, are at a higher risk of developing cardiovascular diseases. Therefore, early diagnosis and treatment of metabolic syndrome in patients with vitiligo to prevent cardiovascular complications were recommended.
A Robust Lane Detection Model Using Vertical Spatial Features and Contextual Driving Information

The quality of detected lane lines has a great influence on the driving decisions of unmanned vehicles. However, during the process of unmanned vehicle driving, the changes in the driving scene cause much trouble for lane detection algorithms. The unclear and occluded lane lines cannot be clearly detected by most existing lane detection models in many complex driving scenes, such as crowded scene, poor light condition, etc. In view of this, we propose a robust lane detection model using vertical spatial features and contextual driving information in complex driving scenes. The more effective use of contextual information and vertical spatial features enables the proposed model more robust detect unclear and occluded lane lines by two designed blocks: feature merging block and information exchange block. The feature merging block can provide increased contextual information to pass to the subsequent network, which enables the network to learn more feature details to help detect unclear lane lines. The information exchange block is a novel block that combines the advantages of spatial convolution and dilated convolution to enhance the process of information transfer between pixels. The addition of spatial information allows the network to better detect occluded lane lines. Experimental results show that our proposed model can detect lane lines more robustly and precisely than state-of-the-art models in a variety of complex driving scenarios.