Miracle-dz/UniFAR-FTUs huggingface dataset:
Information needs and decision‐making preferences of children with cancer

Surveys discussing information needs and decision‐making preferences were administered to 50 children with cancer (ages 8–17) and 60 accompanying parents. Children wanted information on all aspects of their disease and its treatment, particularly prognosis. 76% of children wanted to be told a percent chance for cure, no matter what it was. Only 38% of parents wanted their children to be given this information (p < 0.01). 95% of patients wanted to be told if they were terminally ill. The majority felt that the treatment decision was the physician's. Although 96% of patients did not want to make their own decisions about curative therapy, 63% of adolescents (≥13) wanted to make their own decisions about palliative therapy vs. 28% of younger patients (p = 0.018). Patients felt that people should be allowed to make decisions about participation in medical research at age 14, for treatment of minor medical problems at 16, and to refuse potentially curative therapy for cancer at 17. Parents often want to shield their children from adverse information, but most children want to be fully informed about their disease. Children usually do not want to make decisions about their initial therapy, but many feel that they should decide about palliation.
Increased ribosome density associated to positively charged residues is evident in ribosome profiling experiments performed in the absence of translation inhibitors

ABSTRACT It has been proposed that polybasic peptides cause slower movement of ribosomes through an electrostatic interaction with the highly negative ribosome exit tunnel. Ribosome profiling data—the sequencing of short ribosome-bound fragments of mRNA—is a powerful tool for the analysis of mRNA translation. Using the yeast Saccharomyces cerevisiae as a model, we showed that reduced translation efficiency associated with polybasic protein sequences could be inferred from ribosome profiling. However, an increase in ribosome density at polybasic sequences was evident only when the commonly used translational inhibitors cycloheximide and anisomycin were omitted during mRNA isolation. Since ribosome profiling performed without inhibitors agrees with experimental evidence obtained by other methods, we conclude that cycloheximide and anisomycin must be avoided in ribosome profiling experiments.
IL‐22 and IL‐22 binding protein (IL‐22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections

Interleukin (IL)‐22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate immunity, tissue protection, and repair. IL‐22 may also cause inflammation and abnormal cell proliferation. The binding of IL‐22 to its receptor is competed by IL‐22 binding protein (IL‐22BP), which may limit the deleterious effects of IL‐22. The role of IL‐22 and IL‐22BP in chronic liver diseases is unknown. We addressed this question in individuals chronically infected with schistosomes or hepatitis C virus (HCV). We first demonstrate that schistosome eggs stimulate production of IL‐22 transcripts and inhibit accumulation of IL22‐BP transcripts in schistosome‐infected mice, and that schistosome eggs selectively stimulate production of IL‐22 in cultures of blood leukocytes from individuals chronically infected with Schistosoma japonicum. High IL‐22 levels in cultures correlated with protection against hepatic fibrosis and portal hypertension. To test further the implication of IL‐22/IL‐22BP in hepatic disease, we analyzed common genetic variants of IL22RA2, which encodes IL‐22BP, and found that the genotypes, AA, GG of rs6570136 (P = 0.003; odds ratio [OR] = 2), and CC, TT of rs2064501 (P = 0.01; OR = 2), were associated with severe fibrosis in Chinese infected with S. japonicum. We confirmed this result in Sudanese (rs6570136 GG [P = 0.0007; OR = 8.2], rs2064501 TT [P = 0.02; OR = 3.1]), and Brazilians (rs6570136 GG [P = 0.003; OR = 26], rs2064501 TC, TT (P = 0.03; OR = 11]) infected with S. mansoni. The aggravating genotypes were associated with high IL22RA2 transcripts levels. Furthermore, these same variants were also associated with HCV‐induced fibrosis and cirrhosis (rs6570136 GG, GA [P = 0.007; OR = 1.7], rs2064501 TT, TC (P = 0.004; OR = 2.4]). Conclusions: These results provide strong evidence that IL‐22 protects against and IL‐22BP aggravates liver fibrosis and cirrhosis in humans with chronic liver infections. Thus, pharmacological modulation of IL‐22 BP may be an effective strategy to limit cirrhosis. (Hepatology 2015;61:1321–1331)
Genital manifestation of graft-vs.-host disease: a series of case reports.

INTRODUCTION After hematopoietic stem cell transplantation (HSCT), many patients present genital graft-vs.-host disease (GVHD) that can culminate with sexual problems, which are poorly dimensioned. AIM We hope to draw attention to the need to perform genital biopsy to diagnose genital GVHD, and thus to call attention to the need to incorporate careful attention to sexual health in the treatment of these patients. METHODS Five allogeneic stem cell transplant recipients complaining of coital pain after HSCT were clinically diagnosed for genital GVHD. Genital biopsies were given for histological analysis, and microphotographs of the corresponding marked field in the slide were taken. Specimens were evaluated by the site pathologist and then sent to a reference pathologist, each blinded to the histological findings. A literature search was performed in PubMed/MEDLINE (1966-2009) for cross-sectional and cohort studies or trials related to genital GVHD. Expert opinions peer reviews and case reports were also considered. MAIN OUTCOME MEASURES HSCT, genital GVHD, genital biopsy. RESULTS The biopsy showed evidence of dilated apoptotic cells in the basal layer and detachment of the epithelial lining of the mucosa, hyalinization and thickening of collagen fibers, capillary ectasia, and mononuclear inflammatory infiltrate of the submucosa. Three patients presented vulval lesion such as leucoplasia and ulcer on the large lip. Histological analyses showed evidence of epithelial hyperplasia and influx of inflammatory cells to the epithelial surface, intercellular edema and spongiosis, apoptotic bodies on the basal layer of the epithelium, spongiosis, and nuclear vacuolization. A common treatment based on corticotherapy resulted in complete remission of coetaneous or mucous genital lesions in all five patients. CONCLUSION Genital biopsy is important to differentially diagnose GVHD and secondary symptoms due to hypoestrogenism. Prevention is the most important step in controlling the evolution GVHD in the vagina to prevent vaginal obstruction and sexual dysfunction.
Hepatitis C virus–induced reduction in miR‐181a impairs CD4+ T‐cell responses through overexpression of DUSP6

T cells play a crucial role in viral clearance or persistence; however, the precise mechanisms that control their responses during viral infection remain incompletely understood. MicroRNA (miR) has been implicated as a key regulator controlling diverse biological processes through posttranscriptional repression. Here, we demonstrate that hepatitis C virus (HCV)–mediated decline of miR‐181a expression impairs CD4+ T‐cell responses through overexpression of dual specific phosphatase 6 (DUSP6). Specifically, a significant decline of miR‐181a expression along with overexpression of DUSP6 was observed in CD4+ T cells from chronically HCV‐infected individuals compared to healthy subjects, and the levels of miR‐181a loss were found to be negatively associated with the levels of DUSP6 overexpression in these cells. Importantly, reconstitution of miR‐181a or blockade of DUSP6 expression in CD4+ T cells led to improved T‐cell responses including enhanced CD25 and CD69 expression, increased interleukin‐2 expression, and improved proliferation of CD4+ T cells derived from chronically HCV‐infected individuals. Conclusion: Since a decline of miR‐181a concomitant with DUSP6 overexpression is the signature marker for age‐associated T‐cell senescence, these findings provide novel mechanistic insights into HCV‐mediated premature T‐cell aging through miR‐181a‐regulated DUSP6 signaling and reveal new targets for therapeutic rejuvenation of impaired T‐cell responses during chronic viral infection. (Hepatology 2015;61:1163–1173)
Toxins MazF and MqsR cleave Escherichia coli rRNA precursors at multiple sites

ABSTRACT The endoribonuclease toxins of the E. coli toxin-antitoxin systems arrest bacterial growth and protein synthesis by targeting cellular mRNAs. As an exception, E. coli MazF was reported to cleave also 16S rRNA at a single site and separate an anti-Shine-Dalgarno sequence-containing RNA fragment from the ribosome. We noticed extensive rRNA fragmentation in response to induction of the toxins MazF and MqsR, which suggested that these toxins can cleave rRNA at multiple sites. We adapted differential RNA-sequencing to map the toxin-cleaved 5′- and 3′-ends. Our results show that the MazF and MqsR cleavage sites are located within structured rRNA regions and, therefore, are not accessible in assembled ribosomes. Most of the rRNA fragments are located in the aberrant ribosomal subunits that accumulate in response to toxin induction and contain unprocessed rRNA precursors. We did not detect MazF- or MqsR-cleaved rRNA in stationary phase bacteria and in assembled ribosomes. Thus, we conclude that MazF and MqsR cleave rRNA precursors before the ribosomes are assembled and potentially facilitate the decay of surplus rRNA transcripts during stress.
Poly(ADP-Ribose) polymerase inhibition improves erectile function in diabetic rats.

INTRODUCTION Erectile dysfunction (ED) is a common and hard-to-treat complication of diabetes mellitus (DM). Multiple lines of evidence have shown that poly(ADP-ribose) polymerase (PARP) activation plays an important role in neurovascular dysfunction in diabetes, which is the crucial mechanism for diabetic ED. AIM To investigate the preventive benefit of a PARP inhibitor in a rat model of ED induced by diabetes. METHODS Established streptozotocin-diabetic male Sprague-Dawley rats were given PJ-34, a selective PARP inhibitor, by oral gavage at a dose of 10 mg/kg twice daily for 8 weeks. Erectile responses under electrical stimulation of the cavernous nerve, PARP activity and reactive oxygen species (ROS) production were measured. Nitric oxide synthase (NOS) isoforms were evaluated by Western blot and real-time quantitative PCR. Nuclear factor-kappa B activition and apoptosis in corpus cavernosa (CC) were also investigated. MAIN OUTCOME MEASURES The effects of PARP inhibition on the development of diabetic ED were determined. RESULTS Diabetes markedly attenuated the erectile responses (intracavernosal pressure/mean systemic arterial blood pressure) and these were partially prevented by PJ-34 treatment. Promoted oxidative stress associated PARP activation was found in CC from vehicle-treated diabetic rats. PJ-34 blocked PARP activity and the diabetes-associated ROS generation. Decreased expression and activity of constitutive NOS (cNOS), including endothelial NOS (eNOS) and neuronal NOS (nNOS), associated with enhanced inducible NOS (iNOS) expression and activity were observed in vehicle-treated diabetic rats. Although PJ-34 had no effect on eNOS expression, it significantly prevented the decrease in nNOS expression and cNOS activity, and inhibited iNOS expression and activity in diabetic rats. PARP blockade by PJ-34 to some extent prevented diabetes-associated apoptosis and NF-κB activation. CONCLUSIONS Our results indicate that PARP activation plays an important role in the pathogenesis of diabetic ED and PARP inhibition may be a promising strategy to prevent development of diabetic ED.
Pain Assessment in Children

Although indirect, behavioural measures are the only approaches that can be used in babies, the very young, and those with severe neurological problems. Depending upon age, developmental level and sociocultural considerations, some children will be able to use scales and descriptions that are identical to adults’, such as numerical and visual analogue scales. A variety of scales featuring face scales, colour and poker chip tools and ladders have been adapted for younger children [2] . The range of tools available utilise a combination of aspects of cry, facial expression, posture, body movements and verbal expression. The limitations are that these measures may not discriminate clearly between pain and distress for other reasons. Different tools have been developed for different situations; most have been tested for reliability and validity. The behavioural changes that occur with acute pain seem to differ from those in chronic pain. All these tools are proxy measures using the parents’ or professional’s assessment, not the child’s personal experience. Body charts, drawing and play give children the opportunity to explain more about their pain in ways that might be easier for them than verbal description. Nevertheless, self-report remains the most reliable method. A detailed pain history can provide information about pain and indications as to whether it is visceral, boney or neuropathic in origin. Precipitating and relieving factors may add to the clues about origin. Since past experience of pain may be significant, it may influence pain management. For chronic pain, diaries can help provide a longterm profile. Introduction
Central obesity induces a greater risk of hepatocellular carcinoma than general obesity

cific profile of the individual patient as corresponds to so-called “personalized” or “stratified” medicine. Finally, as Yang et al. mention, if there is evidence of significant portal hypertension (esophageal varices or ascites), the evaluation of portal pressure is not needed. However, it should be noted that absence of varices or ascites does not at all indicate absence of portal hypertension, which should be confirmed by specific investigations. In that sense, we have recently shown that elastography may confirm or rule out clinically significant portal hypertension in a substantial proportion of patients. Also, in some cases, the combination of ultrasonographic findings with low platelet count may also provide proper confirmation of the risky profile. As a whole, assessment of portal pressure should be a cornerstone of the evaluation of potential candidates for surgical resection. Though key in conventional clinical practice, it is also of utmost importance in research studies. If any clinical or molecular parameter is aimed to correlate with the outcome of the patients and portal pressure consideration is not in place, the value of the findings is at risk of significant bias.
The uncoupling of catalysis and translocation in the viral RNA-dependent RNA polymerase

ABSTRACT The nucleotide addition cycle of nucleic acid polymerases includes 2 major events: the pre-chemistry active site closure leading to the addition of one nucleotide to the product chain; the post-chemistry translocation step moving the polymerase active site one position downstream on its template. In viral RNA-dependent RNA polymerases (RdRPs), structural and biochemical evidences suggest that these 2 events are not tightly coupled, unlike the situation observed in A-family polymerases such as the bacteriophage T7 RNA polymerase. Recently, an RdRP translocation intermediate crystal structure of enterovirus 71 shed light on how translocation may be controlled by elements within RdRP catalytic motifs, and a series of poliovirus apo RdRP crystal structures explicitly suggest that a motif B loop may assist the movement of the template strand in late stages of transcription. Implications of RdRP catalysis-translocation uncoupling and the remaining challenges to further elucidate RdRP translocation mechanism are also discussed.
Sexual behaviors, condom use, and sexual health of Americans over 50: implications for sexual health promotion for older adults.

INTRODUCTION In the contemporary U.S., men and women are living longer and healthier lives. As such, many people spend greater portions of their lives as sexually active individuals. Yet, little is known about the myriad of ways that older adults experience their sexual lives. AIM This study sought to assess the context and frequency of sexual behaviors, condom use, sexual pleasure, and sexual experience of men and women over age 50. METHODS Information regarding the sexual experiences of a nationally representative sample of men and women over age 50 within the past year was examined. MAIN OUTCOME MEASURES Sexual behavior over the past year was assessed in relation to several situational and contextual characteristics (e.g., event location, type of partner, health status, condom use). Participants were also asked about their experience (i.e., pleasure, arousal, pain, lubrication/erectile difficulties, and orgasm) during their most recent partnered sexual event. Bivariate or ordinal logistic regression models were used to investigate the relationship of age, health and partner status to sexual frequency and experience. RESULTS Although sizable proportions (20-30%) of both men and women remained sexually active well into their 80s age was related to a lower likelihood of solo and most partnered sexual behaviors. When controlling for age, relationship status, and health remained significant predictors of select sexual behaviors. The participant's evaluation of their most recent sexual experience in terms of arousal, erectile difficulty, and orgasm all declined with age. Health status was related to men's evaluation of the experience. Relationship status was the most consistent predictor of women's evaluation of the experience. Condom use rates remained low for participants across age groups. CONCLUSION Many older adults continue be sexually active well into advanced age (80+). Thus, providers need to be attentive to the diverse sexual health needs of older adults.
Sex difference in oral disease of millet agriculturalists from the Take-vatan lineage of the recent Bunun tribe of Taiwan

Biological anthropologists have repeatedly demonstrated a sex difference of caries prevalence in past societies and have often ascribed this difference to cultural factors related to the sexual division of labor, as well as to biological factors stemming from the female reproductive function. Even though archaeological and historical evidence can hint at the prevailing living conditions, they are not detailed enough to confirm the cultural factors influencing oral disease. For this, skeletal remains in which the prevailing subsistence patterns have been documented by cultural anthropologists must be studied. This study demonstrates sex-specific oral disease prevalence (caries, antemortem tooth loss, periapical abscess, alveolar resorption, and calculus accretion) as well as degree of dental attrition, using the recent Bunun skeletal assemblage, one of the Taiwanese aboriginals. During Japanese rule, cultural anthropologists recorded that the staple product of the Bunun tribe was foxtail millet. Males were responsible for cultivation and hunting, while females were responsible for gathering and preparing foods. The results of this study showed the relatively high morbidity of oral disease, except periapical abscess, regardless of sex. The frequency of females suffering caries and alveolar resorption was significantly greater compared to that of males, and the inverse was true for calculus. Taking into account the fact that the Bunun tribe depend greatly on vegetable foods and smoke heavily, their high morbidity of oral disease is understandable. The combination of their higher morbidity in alveolar resorption and calculus is comparable to the Southeast Asian groups chewing betel nuts documented in previous studies. The sex-specific caries prevalence is believed to be related to the Bunun’s typical and strict sexual division of labor. The inconsistency of the sex difference patterns between alveolar resorption and calculus might be related to the multifactorial origin of the alveolar resorption.
Focusing "hot" or focusing "cool": attentional mechanisms in sexual arousal in men and women.

INTRODUCTION Knowledge about the regulation of sexual emotion may add to the understanding of sexual problems such as diminished sexual desire and hypersexuality. AIM To investigate the regulation of sexual arousal by means of attentional focus in healthy sexually functional men and women. METHOD Using a habituation design with attentional strategies, it was investigated whether a focus on hot, emotional information of sexual stimuli would sustain or amplify sexual responses, whereas a focus on cool, cognitive information would weaken sexual responses. MAIN OUTCOME MEASURES Genital response (in women measured by vaginal photoplethysmography assessing vaginal pulse amplitude, and in men measured by mechanical penile strain gauge assessing penile circumference) and subjective report of sexual arousal and absorption. RESULTS Attenuation of sexual feelings by attentional focus was observed, with stronger sexual feelings under the hot focus condition than under the cool focus condition. Also, sexual feelings diminished during repeated erotic stimulation, and increased with the introduction of novel stimulation, indicating habituation and novelty effects. Contrary to the expectations, the hot attentional focus did not preclude habituation of sexual arousal. CONCLUSIONS Attentional focus has substantial regulatory effects on subjective sexual arousal. Taking a participant and emotion-oriented focus rather than a spectator and stimulus-oriented focus while viewing erotic stimuli, enhances feelings of sexual arousal. Implications for the treatment of hypoactive sexual desire, sexual arousal disorder, and hypersexuality are discussed, as well as future directions for studying regulation of sexual emotion.
Valproic acid‐induced hepatotoxicity in alpers syndrome is associated with mitochondrial permeability transition pore opening‐dependent apoptotic sensitivity in an induced pluripotent stem cell model

Valproic acid (VPA) is widely used to treat epilepsy, migraine, chronic headache, bipolar disorder, and as adjuvant chemotherapy, but potentially causes idiosyncratic liver injury. Alpers‐Huttenlocher syndrome (AHS), a neurometabolic disorder caused by mutations in mitochondrial DNA polymerase gamma (POLG), is associated with an increased risk of developing fatal VPA hepatotoxicity. However, the mechanistic link of this clinical mystery remains unknown. Here, fibroblasts from 2 AHS patients were reprogrammed to induced pluripotent stem cells (iPSCs) and then differentiated to hepatocyte‐like cells (AHS iPSCs‐Hep). Both AHS iPSCs‐Hep are more sensitive to VPA‐induced mitochondrial‐dependent apoptosis than controls, showing more activated caspase‐9 and cytochrome c release. Strikingly, levels of both soluble and oligomeric optic atrophy 1, which together keep cristae junctions tight, are reduced in AHS iPSCs‐Hep. Furthermore, POLG mutation cells show reduced POLG expression, mitochondrial DNA (mtDNA) amount, mitochondrial adenosine triphosphate production, as well as abnormal mitochondrial ultrastructure after differentiation to hepatocyte‐like cells. Superoxide flashes, spontaneous bursts of superoxide generation, caused by opening of the mitochondrial permeability transition pore (mPTP), occur more frequently in AHS iPSCs‐Hep. Moreover, the mPTP inhibitor, cyclosporine A, rescues VPA‐induced apoptotic sensitivity in AHS iPSCs‐Hep. This result suggests that targeting mPTP opening could be an effective method to prevent hepatotoxicity by VPA in AHS patients. In addition, carnitine or N‐acetylcysteine, which has been used in the treatment of VPA‐induced hepatotoxicity, is able to rescue VPA‐induced apoptotic sensitivity in AHS iPSCs‐Hep. Conclusion: AHS iPSCs‐Hep are more sensitive to the VPA‐induced mitochondrial‐dependent apoptotic pathway, and this effect is mediated by mPTP opening. Toxicity models in genetic diseases using iPSCs enable the evaluation of drugs for therapeutic targets. (Hepatology 2015;61:1730‐1739)