Miracle-dz/UniFAR-FTUs huggingface dataset:
Process Improvement for Pediatric Supportive Care

The death of a child is one of the most painful experiences a parent can endure. Highlighted in a report issued by the Institute of Medicine, there is a need to develop strategies for supporting health care workers dealing with perception, knowledge, and involvement in pediatric supportive care. Research has shown that staff members do not always feel comfortable dealing with issues of supportive care; however, after equipping them with knowledge and resources, they will provide the best pediatric supportive care for patients and their families. Most of the studies reviewed a need for communication between staff and the need for support from health care professionals as well as members of other families with critically ill children. The solution at a large academic medical teaching hospital was to educate the childrens’ hospital staff about pediatric supportive care via a computer-based learning module. Follow-up education and reminders were used to reinforce the workflow in making a supportive care consult. The number of encounters and consults were measured and found to improve once the education complete. The communication item on the Press Ganey Survey was also found to have a positive impact on the perception that the interdisciplinary team worked together to care for patients.
Adolescents' reports of their illicit alcohol purchases

Aims : The main aim of this study was to investigate self-reports of the ease with which British adolescents are able to purchase alcohol from different types of outlet. Design, setting, subjects : The study involved a classroom survey of pupils (n = 6980, ages 11-16) attending 11 secondary schools, located in four areas of England. Measures : Respondents completed a confidential questionnaire assessing alcohol purchasing behaviour, alcohol consumption and related factors. Findings : Overall, 37% of the sample were regular (weekly) drinkers, and 21% of the sample (56% of drinkers) reported buying alcohol; over 70% of drinkers had at some time attempted to buy alcohol. These figures increased linearly with age. Among the current alcohol buyers, alcohol was purchased to a roughly equal extent in off-licences, corner shops and pubs, with very little use of supermarkets; the use of pubs increased with age, while the use of other outlets, particularly corner shops decreased with age. Just over half of drinkers had been refused sale; this was reported to occur a little less frequently in corner shops than in the other types of outlet. Most of the buyers (67%) were never or very rarely asked their age; girls were less likely to be challenged on age than boys. Few respondents were familiar with the drinks industry's 'Prove-It' proof of age card. Respondents reported low levels of anxiety or guilt in relation to alcohol purchase, but tended to avoid outlets where they were likely to be challenged. Conclusions : Alcohol appears to be readily available, from a variety of different types of outlet, to under-aged adolescents who wish to purchase it. Children attempting to buy alcohol are rarely challenged on their age, and little use is being made of the 'Prove It' card, at least in the areas where this study took place.
Understanding the impact of complicated grief on combat related posttraumatic stress disorder, guilt, suicide, and functional impairment in a clinical trial of post‐9/11 service members and veterans

Complicated grief (CG) is a bereavement‐specific syndrome distinct from but commonly comorbid with posttraumatic stress disorder (PTSD). While bereavement is common among military personnel (Simon et al., 2018), there is little research on the impact of CG comorbidity on PTSD treatment outcomes.
Tabata‐style functional exercise increases resting and postprandial fat oxidation but does not reduce triglyceride concentrations

What is the central question of this study? What are the metabolic impacts of high intensity functional Tabata exercise? What is the main finding and its importance? Tabata exercise with high intensity functional movements causes increases in fasted and postprandial fat oxidation the day after exercise without altering postprandial triglyceride concentrations. These results support the usage of a Tabata‐style high intensity functional exercise to improve postprandial fat oxidation.
SlGRAS4 mediates a novel regulatory pathway promoting chilling tolerance in tomato

Summary Tomato (Solanum lycopersicum L.) plants are cold‐sensitive, and the fruit are susceptible to postharvest chilling injury when stored at low temperature. However, the mechanisms underlying cold stress responses in tomato are poorly understood. We demonstrate that SlGRAS4, encoding a transcription factor induced by low temperature, promotes chilling tolerance in tomato leaves and fruit. Combined genome‐wide ChIP‐seq and RNA‐seq approaches identified among cold stress‐associated genes those being direct targets of SlGRAS4 and protein studies revealed that SlGRAS4 forms a homodimer to self‐activate its own promoter. SlGRAS4 can also directly bind tomato SlCBF promoters to activate their transcription without inducing any growth retardation. The study identifies the SlGRAS4‐regulon as a new cold response pathway conferring cold stress tolerance in tomato independently of the ICE1‐CBF pathway. This provides new track for breeding strategies aiming to improve chilling tolerance of cultivated tomatoes and to preserve sensory qualities of tomato fruit often deteriorated by storage at low temperatures.
Alternative Splicing of the SLCO1B1 Gene: An Exploratory Analysis of Isoform Diversity in Pediatric Liver

The hepatic influx transporter OATP1B1 (SLCO1B1) plays an important role in the disposition of endogenous substrates and drugs prescribed to children. Alternative splicing increases the diversity of protein products from > 90% of human genes and may be triggered by developmental signals. As concentrations of several endogenous OATP1B1 substrates change during growth and development, with this exploratory study we investigated age‐dependent alternative splicing of SLCO1B1 mRNA in 97 postmortem livers (fetus‐adolescents). Twenty‐seven splice variants were detected; 10 were confirmed by additional bioinformatic analyses and verified by quantitative polymerase chain reaction, and selected for detailed analysis based on relative abundance, association with age, and overlap with an adjacent gene. Two splice variants code for reference OATP1B1 protein, and eight code for truncated proteins. The expression of eight isoforms was associated with age. We conclude that alternative splicing of SLCO1B1 occurs frequently in children; although the functional consequences remain unknown, the data raise the possibility of a regulatory role for alternative splicing in mediating developmental changes in drug disposition.
Development of tablet personal computer-based cognitive training programs for children with developmental disabilities whose cognitive age is less than 4 years

Abstract This study was to develop tablet personal computer-based cognitive training programs for children with developmental disabilities whose cognitive age is less than 4 years. Twelve cognitive training programs (named Injini) were designed comprising cognitive domains that included attention, visual and auditory perception, memory, executive function, language, and reasoning. In addition, programs related to learning experiences, such as self-regulation, role play, learning of number, and letter/shape concepts, comparison, classification, and pattern matching, were included. Six of 12 programs comprised approximately 10 levels for each program, with different difficulty levels. Other programs consisted of universal tasks that did not have a difficulty level. To ensure that the difficulty level was appropriate, we pre-tested the pilot version of Injini among 80 children with typical development aged 18 to 41 months. After modifying the pilot version, we developed the final version and tested it among 80 children with cognitive impairment whose cognitive age was 18 to 41 months. All children were assessed using the Bayley Scales of Infant and Toddler Development to determine their development and cognitive age. The difficulty level analyses in children with typical development revealed several inappropriate results wherein the success rate did not decrease with increase in level in some programs. After adjusting the difficulty level, the analyses in children with cognitive impairment demonstrated that the success rate gradually decreased with increasing level in all programs. Cognitive training programs for children with developmental disabilities were successfully developed.
Effect of comorbid anxiety and depression in complicated grief on perceived cognitive failures

Bereavement is associated with cognitive difficulties, but it is unclear whether these difficulties are associated with normative and/or complicated grief (CG) and how comorbid depression and anxiety contribute to them. Self‐reported “minor errors in thinking” (i.e., cognitive failures) may manifest following bereavement and be differentially affected by CG, anxiety, and depression.
Evaluative conditioning of artificial grammars: Evidence that subjectively-unconscious structures bias affective evaluations of novel stimuli.

Evaluative conditioning (EC) refers to the acquisition of emotional valence by an initially neutral stimulus (conditioned stimulus [CS]) after being paired with an emotional stimulus (unconditioned stimulus [US]). An important issue regards whether, when participants are unaware of the CS-US contingency, the affective valence can generalize to new stimuli that share similarities with the CS. Previous studies have shown that generalization of EC effects appears only when participants are aware of the contingencies, but we suggest that this is because (a) the contingencies typically used in these studies are salient and easy to detect consciously, and (b) the performance-based measures of awareness (so-called "objective measures"), typically used in these studies, tend to overestimate the amount of available conscious knowledge. We report a preregistered study in which participants (N = 217) were exposed to letter strings generated from two complex artificial grammars that are difficult to decipher consciously. Stimuli from one grammar were paired with positive USs, whereas those from the other grammar were paired with negative USs. Subsequently, participants evaluated new, previously unseen, stimuli from the positively conditioned grammar more positively than new stimuli from the negatively conditioned grammar. Importantly, this effect appeared even when trial-by-trial subjective measures indicated lack of relevant conscious knowledge. We provide evidence for the generalization of EC effects even without subjective awareness of the structures that enable those generalizations. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
IQGAP1 restrains T‐cell cosignaling mediated by OX40

A costimulatory signal from the tumor necrosis factor receptor (TNFR) family molecule OX40 (CD134), which is induced on activated T cells, is important for T‐cell immunity. Aberrant OX40 cosignaling has been implicated in autoimmune and inflammatory disorders. However, the molecular mechanism by which the OX40 cosignaling regulates the T‐cell response remains obscure. We found that OX40 associated with a scaffold protein, IQ motif‐containing GTPase‐activating protein 1 (IQGAP1) after ligation by its ligand OX40L. Naïve CD4+ T cells from Iqgap1−/− mice displayed enhanced proliferation and cytokine secretion upon receiving OX40 cosignaling. A C‐terminal IQGAP1 region was responsible for its association with OX40, and TNFR‐associated factor 2 (TRAF2) bridged these two proteins. The enhanced cytokine response in Iqgap1−/− T cells was restored by the expression of the C‐terminal IQGAP1. Thus, the IQGAP1 binding limits the OX40 cosignaling. Disease severity of experimental autoimmune encephalomyelitis (EAE) was significantly exacerbated in Iqgap1−/− mice as compared to wild‐type mice. Additionally, recipient mice with Iqgap1−/− donor CD4+ T cells exhibited significantly higher EAE scores than those with their wild‐type counterparts, and OX40 blockade led to a significant reduction in the EAE severity. Thus, our study defines an important component of the OX40 cosignaling that restricts inflammation driven by antigen‐activated T cells.
Comparative effectiveness of tamoxifen, toremifene, letrozole, anastrozole, and exemestane on lipid profiles in breast cancer patients

Abstract Background: Adjuvant endocrine therapy is a vital portion of postoperative comprehensive treatment for breast cancer patients. In recent years, studies have shown that endocrine therapy has a certain impact on the serum lipids of breast cancer patients, and the changes of lipid profiles may bring a series of problems. However, very few studies focus on this issue to date. The results of these studies are inconsistent, and the influence of different adjuvant endocrine modalities on lipid profiles still remains controversial. In order to better explore this issue, we conduct this network meta-analysis. Method: The protocol followed preferred reporting items for systematic reviews and meta-analyses protocols. Three main databases (PubMed, Embase, and the Cochrane Library) will be searched systematically for eligible randomized controlled trials without language restriction. In addition, a manual search of the references of relevant published studies will also be considered. Two reviewers will conduct studies selection, data extraction, and risk of bias assessment independently. The primary outcome is the variation of biochemical parameters – the serum lipid profiles (cholesterol, triglyceride, high-density lipoprotein, low low-density lipoprotein). Results: The results will provide useful information about the side effects of different adjuvant endocrine drugs on lipid profiles in postoperative breast cancer patients (estrogen receptor-positive and/or progesterone receptor-positive). Conclusion: The findings of this study will be published in a peer-reviewed journal. Prospero Registration Number: CRD42019129850.
Conversion and Stability of New Metabolites of Paralytic Shellfish Toxins under Different Temperature and pH Conditions.

A number of new C-11 hydroxyl metabolites (so-called M-toxins) of paralytic shellfish toxins (PSTs) have been discovered in contaminated shellfish, and trace amounts have also been detected in some strains of PST-producing microalgae. To investigate the chemical conversion and stability of M-toxins, mussel extracts were purified with solid-phase extraction cartridges (Oasis HLB) and Bio-gel P-2 resin columns, and four partially purified M-toxin fractions were stored at different temperatures (-20℃, 4℃, 20℃) and pH values (3, 4, 5). The concentrations and profiles of M-toxins in these fractions were analyzed using LC-MS/MS for 27 weeks. Results further confirmed the chemical conversion pathway M1→M3→M5, and determined for the first time two new transformation pathways: M2→M4→M6 and neosaxitoxin (NEO)→M10. The half-lives of M1, M2, M4 and M10 were calculated using a first-order degradation kinetics model, which indicated that the degradation of all M-toxins was dependent on temperature and pH, increasing with rising temperature and pH. Compared to M4 and M10, M1 was more sensitive to temperature, followed by M2. Results suggest that M-toxins should be maintained at low temperature (-20℃) and low pH (3) for their prolonged storage. M-toxins were less stable than all the common analogues of PSTs, which may be beneficial for shellfish to achieve rapid detoxification through transformation of PSTs to M-toxins. These new findings are of significance as they enable further understanding of the metabolism of PSTs and their detoxification mechanisms in contaminated shellfish.
Recent out-of-Africa migration of human herpes simplex viruses.

Herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2) are ubiquitous human pathogens. Both viruses evolved from simplexviruses infecting African primates and they are thus thought to have left Africa during early human migrations. We analyzed the population structure of HSV-1 and HSV-2 circulating strains. Results indicated that HSV-1 populations have limited geographic structure and the most evident clustering by geography is likely due to recent bottlenecks. For HSV-2, the only level of population structure is accounted for by the so-called "worldwide" and "African" lineages. Analysis of ancestry components and nucleotide diversity, however, did not support the view that the worldwide lineage followed early humans during out-of-Africa dispersal. Although phylogeographic analysis confirmed an African origin for both viruses, molecular dating with a method that corrects for the time-dependent rate phenomenon indicated that HSV-1 and HSV-2 migrated from Africa in relatively recent times. In particular, we estimated that the HSV-2 worldwide lineage left the continent in the 18th Century, which corresponds to the height of the transatlantic slave trade, possibly explaining the high prevalence of HSV-2 in the Americas (second highest after Africa). The limited geographic clustering of HSV-1 makes it difficult to date its exit from Africa. The split between the basal clade, containing mostly African sequences, and all other strains was dated at ∼5,000 years ago. Our data do not imply that herpes simplex viruses did not infect early humans, but show that the worldwide distribution of circulating strains is the result of relatively recent events.
The Prevalence of Paraphilic Interests in the Czech Population: Preference, Arousal, the Use of Pornography, Fantasy, and Behavior

ABSTRACT The number of population-based studies focused on the prevalence of paraphilic sexual interests in men is very low and for women, the subject remains largely unexplored. The two main aims of this study are to investigate the prevalence of paraphilias and to explore sex differences in an online representative sample of Czech men and women using various dimensions of sexual experience. We collected data about sexual motivations and behavior from a representative online sample of 10,044 Czechs (5,023 men and 5,021 women). In a standardized online interview, participants answered questions about selected dimensions of sexual experience within specific paraphilic patterns: sexual preferences, sexual arousal, sexual fantasies in the past 6 months, pornography use in the past 6 months, and experience with paraphilic behaviors. Our results show that 31.3% of men (n = 1,571) and 13.6% of women (n = 683) admitted to at least one paraphilic preference. Moreover, 15.5% of men and 5% of women reported more than one paraphilic preference. Except for beating/torture and humiliation/submission, in terms of real experience with such behaviors almost all paraphilias were more common among men than among women. Our results indicate that the high prevalence of some paraphilic patterns might render their pathologization problematic.
Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS

Diabetic nephropathy (DN) is the leading cause of end‐stage kidney disease. TGF‐β1/Smad3 signalling plays a major pathological role in DN; however, the contribution of Smad4 has not been examined. Smad4 depletion in the kidney using anti‐Smad4 locked nucleic acid halted progressive podocyte damage and glomerulosclerosis in mouse type 2 DN, suggesting a pathogenic role of Smad4 in podocytes. Smad4 is upregulated in human and mouse podocytes during DN. Conditional Smad4 deletion in podocytes protects mice from type 2 DN, independent of obesity. Mechanistically, hyperglycaemia induces Smad4 localization to mitochondria in podocytes, resulting in reduced glycolysis and oxidative phosphorylation and increased production of reactive oxygen species. This operates, in part, via direct binding of Smad4 to the glycolytic enzyme PKM2 and reducing the active tetrameric form of PKM2. In addition, Smad4 interacts with ATPIF1, causing a reduction in ATPIF1 degradation. In conclusion, we have discovered a mitochondrial mechanism by which Smad4 causes diabetic podocyte injury.
Serological surveillance and clinical investigation of glanders among indigenous equines in India from 2015 to 2018.

Equine glanders is an infectious and notifiable bacterial disease caused by Burkholderia mallei. The disease has been reported in South American, African and Asian countries including India. Here, we present the outcome of glanders sero-surveillance carried out between January 2015 and December 2018 to know the status of equine glanders among different states in India. A total of 102,071 equids sera from 299 districts of twenty one states and one union territory were tested for glanders. Samples were screened with Hcp1 indirect ELISA followed by confirmatory diagnosis by CFT. During this four year surveillance, a total of 932 glanders positive cases were detected from 120 districts of 12 states. The study also revealed increasing trend of glanders from 2016 onward with maximum occurrence in Northern India. Overall sero-prevalence ranged between 0.62% (95% CI, 0.52-0.72) and 1.145% (95% CI, 1.03-1.25). Seasonal shifting from winter to summer (March to June) coincided with highest number glanders incidence with corresponding sero-prevalences of 1.2% (95% CI, 1.09-1.30). The present surveillance unveils territorial ingression of glanders to six states like Jammu & Kashmir, Gujarat, Rajasthan, Madhya Pradesh, Delhi and Tamil Nadu. In addition, re-emerging cases have been reported in Maharashtra, Haryana and Punjab after a gap of 10 years. Lack of awareness, little veterinary care and unrestricted movement of equids across state borders might have led to the introduction and establishment of the infection to these states. We believe that information from this study will provide a baseline data on glanders for devising surveillance and control strategies in India. Being a zoonotic disease, the persistence of glanders poses a potential threat to occupationally exposed humans especially equine handlers and veterinarians. Therefore, targeted surveillance of human population from each glanders outbreak is also recommended.
A functional twintron, ‘zombie’ twintrons and a hypermobile group II intron invading itself in plant mitochondria

Abstract The occurrence of group II introns in plant mitochondrial genomes is strikingly different between the six major land plant clades, contrasting their highly conserved counterparts in chloroplast DNA. Their present distribution likely reflects numerous ancient intron gains and losses during early plant evolution before the emergence of seed plants. As a novelty for plant organelles, we here report on five cases of twintrons, introns-within-introns, in the mitogenomes of lycophytes and hornworts. An internal group II intron interrupts an intron-borne maturase of an atp9 intron in Lycopodiaceae, whose splicing precedes splicing of the external intron. An invasive, hypermobile group II intron in cox1, has conquered nine further locations including a previously overlooked sdh3 intron and, most surprisingly, also itself. In those cases, splicing of the external introns does not depend on splicing of the internal introns. Similar cases are identified in the mtDNAs of hornworts. Although disrupting a group I intron-encoded protein in one case, we could not detect splicing of the internal group II intron in this ‘mixed’ group I/II twintron. We suggest the name ‘zombie’ twintrons (half-dead, half-alive) for such cases where splicing of external introns does not depend any more on prior splicing of fossilized internal introns.