Miracle-dz/UniFAR-FTUs huggingface dataset:
Palbociclib plus cetuximab versus placebo plus cetuximab in platinum-resistant, cetuximab-naive, HPV-unrelated head and neck cancer: A double-blind randomized phase II trial (PALATINUS).

6013 Background: Cetuximab monotherapy results in a median overall survival (OS) of approximately 6 months (mo) in platinum-resistant recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). HNSCC unrelated to human papillomavirus (HPV) is driven by hyperactivation of the CDK4/6 and cyclin D1 (CD1) regulatory complex, resulting in cell cycle progression and tumor growth, suggesting that CDK4/6 inhibition can be a rational therapeutic strategy in this setting. Palbociclib (PAL) is a selective CDK4/6 inhibitor that may reverse cetuximab resistance by countering the actions of deregulated CD1. PAL plus an epidermal growth factor receptor inhibitor synergistically reduced cell viability of HPV-unrelated HNSCC cell lines. In a single-arm, multicenter trial of platinum-resistant, cetuximab-naive, HPV-unrelated HNSCC, PAL in combination with cetuximab resulted in a median OS of 9.5 mo. Methods: In a double-blind randomized phase II trial, patients (pts) with platinum-resistant, cetuximab-naïve, HPV-unrelated HNSCC were treated with cetuximab plus either PAL (arm A) or placebo (arm B). Pts were stratified by performance status (PS) and prior immunotherapy (IT). 120 pts were required for 1:1 randomization to have ≥ 80% power to detect a hazard ratio (HR) of 0.6 (corresponding to a median OS of 10 mo in arm A and 6 mo in arm B) using a 1-sided log-rank test P=0.10). Key secondary endpoints included progression-free survival (PFS), adverse events (AEs), and p16 status. Results: Pts (n=125) were randomized (arm A, 65; arm B, 60). PS and prior IT were balanced between the arms. Median (95% CI) follow-up for OS was 15.9 (15.0–19.4) mo. Median OS was 9.7 (7.3–13.9) mo in arm A and 7.8 (6.7–10.6) mo in Arm B (stratified by PS: HR=0.82 [95% CI, 0.54–1.25], P=0.18). Median PFS was 3.9 mo in arm A and 4.6 mo in arm B (stratified by PS: HR=1.00 [0.7–1.5], P=0.5). Hematologic AEs were more common in arm A. Only 11 pts (9%) received IT after being treated on the trial. Conclusions: Among pts with platinum-resistant, HPV-unrelated HNSCC, PAL plus cetuximab resulted in a trend of prolongation of median OS compared with cetuximab. Clinical trial information: NCT02499120.
A Very Uncommon Case of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) describes a rare, progressive disease of the pulmonary vasculature, involving a group of clinical conditions that result in precapillary pulmonary hypertension (PH). PAH is characterized by proliferative vasculopathy, and subsequent right heart failure. For the past several decades research has focused on identification of underlying molecular causes of this disease. Recently, there have been a number of reported cases of patients with scurvy developing pulmonary arterial hypertension. Thus, it has been hypothesized that vitamin C deficiency results in non-hypoxic activation of hypoxia inducible transcription factors (HIF) and low nitric oxide (NO) level in the pulmonary vasculature, leading to subsequent pulmonary vasculopathy and an exaggerated pulmonary vasoconstrictive response. Immediate supplementation of vitamin C is considered the definitive treatment, preventing an otherwise fatal outcome. In this paper, we describe a patient with a fatal case of scurvy related PAH, who was admitted with ecchymosis, oral ulceration, and dyspnea.
Representasi Perlawanan Rasisme Dalam Film The Help (Analisis Semiotika Roland Barthes)

Film sebagai representasi menghadirkan kembali realita yang berkembang dalam masyarakat. Film The Help merupakan film yang menggambarkan mengenai pembantu ras kulit hitam dan orang ras kulit putih melawan tindakan diskriminasi dan rasis majikan kulit putih. Penelitian ini bertujuan untuk melihat bagaimana bentuk sikap perlawanan rasisme digambarkan dalam film The Help. Peneliti menggunakan pendekatan kualitatif dengan metode analisis semiotika Roland Barthes untuk meneliti dan mengkaji tanda-tanda dalam film The Help. Ada tiga tingkatan tanda dalam semiotika Roland Barthes, yakni tanda denotasi, tanda konotasi, dan mitos. Semiotika Roland Barthes digunakan untuk menganalisis adegan-adegan yang menampilkan perlawanan terhadap rasisme. Hasil penelitian menunjukkan bahwa bentuk-bentuk perlawanan terjadi dalam tiga bentuk kategori. Pertama, perlawanan secara individual. Kedua perlawanan secara institusional, dan ketiga adalah kesetaraan antara orang ras kulit putih dan orang ras kulit hitam. Perlawanan secara indidual terjadi dalam bentuk verbal dan non verbal. Perlawanan secara verbal terjadi dengan cara mencemooh, mengejek, berkata kasar, mengancam, mengumpat. Perlawanan secara non verbal dengan cara melotot, dahi mengernyit, menggertakkan gigi, menyilangkan lengan di dada, menatap wajah majikan, dan menerbitkan buku yang berisi tentang curahan perasaan pembantu ras kulit hitam. Perlawanan secara institusional terjadi dengan cara penggunaan kamar mandi majikan, penggunaan peralatan makan yang sama. Kesetaraan antara orang ras kulit hitam dan orang ras kulit putih dilakukan dengan cara kontak fisik, penolakan panggilan hormat, bersikap baik dan menghargai. Sebagian besar simbol-simbol perlawanan terlihat melalui tindakan tokoh dalam film The Help.
Extending postoperative opioid analgesia in dogs 1. Oral drug administration

Although opioid drugs are extensively used for postoperative analgesia in dogs, their administration is generally restricted to the period in which the animal is hospitalised. Unfortunately, this limits the ability to provide multimodal pain relief in the home environment, which may lead to inadequate analgesia and consequent ‘break-through’ pain. This article, the first in a series of two, discusses the uses and limitations of oral opioid administration for extending postoperative analgesia beyond the hospitalisation period. The second article, to be published in a subsequent issue of In Practice, will focus on the role of transdermal opioid delivery for this purpose.
Statistical analysis of sequence populations in virology and immunology (Statistische Analyse von Sequenzpopulationen in der Virologie und Immunologie)

In this thesis I have examined various topics regarding the relationship between viruses and the human immune system. I expanded and refined a tool (which can now be found as R-package SeqFeatR on C-RAN) for the analysis of sequence data and features of this sequences like HLA type or tropism (see chapter 4) and checked with this tool if there are differences between some multiple correction approaches for sequence data, and how Bayesian inference could be used in this context (see chapter 5). It could be shown that Bayesian inference is superior to the frequentistic methods for this kind of problem, because multiple correction approaches ignore the fact that different positions in a sequence alignment may be connected in the protein product of this sequence and are therefor not independent. Furthermore, I have examined sequences from HCV with a form of bootstrap algorithm to find sequence areas which can be used in unknown transmission cases in court. Two areas were found, one in the hypervariable region and the other at the end of the non-structural protein NS5B (see chapter 9). Proteasomal cleavage of alien amino acid sequences inside human cells leads to a presentation of fragments of these sequences on the surface of the cell as epitopes. To present such a fragment, not only must it bind to the MHC, but also needs to be in the correct length to be presented. Therefore viral evolution should favor those viruses, which cannot be cut into presentable epitopes. With epitope data from IEDB and predicted viral sequences which bind the MHC, I searched for amino acids inside the flanking regions around the epitope that may indicate a possible escape mutation against the proteasomal cleavage processes. Fourteen such amino acids and positions were found (see chapter 7). I created a model of HBV reverse transcriptase to check if mutations in certain positions could influence binding with the nucleotide analogue reverse transcriptase inhibitor Tenofovir. Mutations which were inside the binding pocket for Tenofovir showed, in an experimental design by the group of Mengji Lu, a decreased affinity towards the drug (see chapter 10). Together with Ralf Kuppers group I examined NGS from different types of B cells to search for almost identical sequences between those. We found similar to identical sequences from two, three and even four kinds of cells in the blood samples of both donors (see chapter 6).
A translational approach to the renin-angiotensin-aldosterone system in heart failure

The renin-angiotensin-aldosterone system (RAAS) is a well-studied neurohormonal cascade that plays key role in various homeostatic mechanisms, such as blood pressure control and tissue perfusion balance. Dysregulation of RAAS has been involved in the pathogenesis of various cardiovascular disorders. Heart failure (HF) is a very common cardiovascular disease with significant morbidity and mortality. RAAS participates in the pathogenesis of HF and it has been indicated as important therapeutic target. Angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRAs) and recently angiotensin receptor-neprilysin inhibitors (ARNIs) are the most common used RAAS-modifying therapies that significantly improved the mortality and the morbidity of patients with HF and reduced ejection fraction. On the other hand, the aforementioned therapeutic choices failed to show promising results in HF with preserved ejection fraction. This article discusses current knowledge on the role of RAAS modulation in HF and our therapeutic options.
Leishmaniasis in the Eastern Mediterranean Region

Leishmaniasis is recognized as an important public health problem in some Member States of the Eastern Mediterranean Region owing to its considerable impact on morbidity and its potential to spread in epidemics, which impose a heavy burden on national health services. The increased incidence of leishmaniasis in countries of the Region is due to several reasons including influx of nonimmune population into natural foci of transmission, changes in ecology of vectors and reservoir host, reduction in the use of residual insecticides for the control of malaria and improvements in diagnosis and reporting of positive cases
Évaluation en médecine de soins primaires chez des patients entre 15 et 45 ans de l'apport de l'auto-questionnaire SCOFF-F dans le dépistage des troubles du comportement alimentaire en comparaison aux pratiques habituelles

Rationnel : Les troubles du comportement alimentaire (TCA), frequents chez les jeunes femmes de 15 a 45 ans, sont des maladies complexes souvent associees a une errance diagnostique en soins primaires, source d'une morbi-mortalite elevee. Bien qu'il ait ete demontre qu'un depistage precoce ameliore le pronostic, les TCA sont sous-estimes par les medecins generalistes (MG) en soins primaires par manque ou meconnaissance d'instruments de depistage. L'auto-questionnaire SCOFF-F, recommande par la Haute Autorite de Sante, est un outil qui malgre une excellente sensibilite et specificite pour la detection reste meconnu et peu utilise. Objectif : Notre travail a souhaite evaluer le gain apporte par le SCOFF-F au MG dans le depistage des TCA en comparaison avec sa pratique habituelle en soin primaire chez des patients de 15 a 45 ans. Methode : Les MG ont recrute des patients de 15 a 45 ans les consultant a leur cabinet de ville quel que soient le ou les motifs de consultation. Les patients remplissaient le SCOFF-F en fin de consultation et en parallele, leur MG un questionnaire medical de 6 items portant sur le diagnostic principal et secondaire, le motif de consultation, la connaissance d'un TCA anterieur, la suspicion d'un TCA a l'issue de la visite. Resultats : 14 MG ont participe et ont recrute 210 patients. Selon les pratiques courantes, 14 (6%) patients ont ete consideres comme ayant un diagnostic probable de TCA a la fin de la consultation contre 53 (25%) identifies par le SCOFF-F (score ≥ 2/5). La discordance de depistage etait statistiquement significative (p < 0,0001) avec une optimisation du reperage d'un facteur 13. En comparaison aux patients avec un score de SCOFF-F < 2, les patients avec un SCOFF-F positif avaient un poids actuel et une taille inferieurs (p < 0,05), consultaient peu pour leur desordres ponderaux mais davantage pour des troubles digestifs (p < 0,05) associes a des troubles psychiatriques. Conclusion : Le SCOFF-F est clairement un excellent outil d'aide au depistage precoce pour les praticiens de soins primaires. Apres l'evaluation de l'acceptabilite de ce questionnaire en depistage de routine aupres des patients cibles, une meilleure diffusion de cet outil aupres des MG doit etre envisagee.
A-optimal designs for two-colour cDNA microarray experiments using the linear mixed effects model

Two-colour cDNA microarray experiments help scientist to study the expression level of thousands of genes simultaneously under different conditions. Microarray experiments have different design challenges, such as for example which mRNA samples should be co-hybridized together and which treatment should be labelled with which dye fluorescent. Therefore, a carefully designed microarray experiment to obtain efficient and reliable data so as to assure the precise estimate of parameters that are of interest is needed. The present paper is concerned with A-optimal block designs for two-colour microarray experiments, where array is treated as the experimental block. Linear mixed effects models were used to describe the experiments, by taking the arrays as random effects, when comparisons of all possible pairs of treatments are of particular interest. The numerical results show that the optimal block designs under the linear fixed effects model are not necessarily optimal under the linear mixed effects model setting.
Milieus and Sexual Difference

Irigaray's critique of the phallocentric subject's implicit dependence on the maternal-feminine “outside” is compelling. Her postulation of nonhierarchical sexual difference gives the relational world of woman specificity and Irigaray brings the subject's worldview to earth as merely the relation of the male human to the world. But the focus of her transvaluation remains largely anthropocentric; and she maintains too many aspects of the privilege of the subject's sovereignty as proper to male subjectivity. I suggest that, we need to extend Irigaray and to think sexual difference beyond the human. Drawing from Elizabeth Grosz, Gilles Deleuze, Henri Bergson and Jakob Von Uexküll, I argue that we need to think life beyond the constitution of the organism as the continuous enmeshment of different milieus. Sexual difference is a force of differentiation that articulates relationships between organisms and organs as crucial aspects of many milieus that make up the Earth. Along with the sexually differentiated aspects of milieus, there are rhythms of difference constitutive of milieus that are not sexed. The first section of the essay describes Irigaray's conceptualization of sexual difference between humans. Then I turn to her engagement with the status of nonhuman animals in “Animal Compassion. ” I suggest her approach in this essay is too anthropocentric and move to a discussion of Uexküll's thinking on milieus as a way to extend the concepts of difference and sexual difference into posthuman contexts. The essay concludes by reading Irigaray's concept of difference with Deleuze and Bergson.
Attempted Suicides in South Korea : A Multi-Center Analysis of Causes, Methods, and Psychiatric Diagnoses of Suicidal Attempters in 2013

OBJECTIVES: To examine direct causes of attempted suicides, methods adopted to commit suicide, and psychiatric diagnoses among suicide attempters in South Korea. METHODS: A total of 1359 suicide attempters who had visited emergency department of 17 medical centers due to suicide attempt from May 2013 to Nov 2013 were interviewed using semi-structured questionnaires. RESULTS: Psychiatric symptoms were the most common cause of suicide attempts (62.2%), followed by interpersonal relationships (24.4%). Women attempted suicide more often for interpersonal reasons, whereas men were more likely to do so for financial and jobrelated reasons. Half of participants (55.8%) attempted suicide by drug intoxication, which was more prevalent among females and those who had previous history of psychiatric disease or previous suicide attempt. Men were more likely to use more lethal methods such as pesticide poisoning and gas inhalation than women. Pesticide poisoning was also prevalent among the elderly group and the rural population. Near ninety-five percent (94.5%) of participants received a psychiatric diagnosis : the most frequent diagnosis was depressive disorder. CONCLUSIONS: This is the first nationwide study of cases of attempted suicide. When stratified by age groups, gender, urbanicity, living alone or not, presence of physical illness, previous psychiatric history, and previous suicide attempt, there were significant differences with respect to causes, methods of attempted suicides and psychiatric diagnoses of suicide attempters. Language: ko
Effect of Tomato Rootstock on Hybrid and Heirloom Tomato Performance in a Midwest High Tunnel Production System

High tunnels allow vegetable growers to extend the growing season, increase crop production, and improve produce quality. Tomatoes (Solanum lycopersicum L.) are the most widely grown crops in high tunnels; however, tomato production in high tunnels can be challenging. Continuous cropping in high tunnels can increase soil-borne disease pressure and can lead to soil salinity or nutrient depletion issues. Based on preliminary research, we hypothesized that use of the rootstock ‘RST-04-106-T’ would increase yield and quality of heirloom and hybrid tomato scions compared with nongrafted plants. To test this hypothesis, our research objectives were to assess marketable yields, fruit quality and nutritional value, and plant growth of grafted and nongrafted hybrid and heirloom tomatoes in a high tunnel production system. Grafted and nongrafted ‘Cherokee Purple’ (heirloom) and ‘Mountain Fresh Plus’ (hybrid) tomatoes were grown in the same high tunnel for two seasons (7 May–20 Oct. 2015 and 29 April–7 Oct. 2016) at the Horticulture Research Station in Ames, IA. Grafted plants produced significantly more marketable fruit, although marketable and total fruit weight did not increase significantly. Individual fruit size was unaffected by grafting. Across cultivars, mean soluble solids content (SSC) in fruit was 0.3 °Brix lower in grafted plants as compared with the nongrafted control. Grafting did not affect lycopene content of fruit. Grafting increased stem diameter by an average of 0.8 mm, but overall plant biomass was unaffected. The effect of grafting on leaf chlorophyll concentration (SPAD readings) was mixed. In addition, grafting increased leaf chlorophyll concentration in ‘Cherokee Purple’ but decreased it in ‘Mountain Fresh Plus’ plants. Grafting is a valuable tool in tomato production, but the impact of ‘RST-04-106-T’ rootstock use appears to be specific to certain soil types with high incidence of bacterial wilt.
The role of doctors in smoking cessation: evidence from the Cochrane Library

This article examines the role of doctors in assisting patients who smoke to quit, using evidence from Cochrane systematic reviews of randomised trials. Doctors may help such patients by providing advice, referring patients for counselling and support and by offering pharmacological therapy. Complementary therapies used for smoking cessation include hypnotherapy and acupuncture, but there is a lack of evidence that these interventions have a specific effect in aiding cessation. The number needed to treat (NNT) for simple advice to unselected smokers is 50 - 120. Based on a median no-treatment clinical trial quit rate of 7.5%, the NNT for nicotine replacement therapy is 23 (95% CI 20 to 27), for the antidepressant Bupropion 18 (95% CI 14 to 23), and for the nicotinic partial agonist Varenicline 10 (95% CI 7 to 14). These numbers compare favourably with other preventive healthcare interventions. There remains wide variations in the extent to which these interventions are available in different healthcare systems.
Oxycodone as a Component of Multimodal Analgesia Post‐Caesarean Section in Australia and New Zealand

There is a perception that oral oxycodone is becoming a popular choice for post‐caesarean section analgesia. There are a lack of published data quantifying the use of oxycodone and other drugs for post‐caesarean section analgesia in Australasian practice.
Selective Amino Acid-Only in Vivo NMR: A Powerful Tool To Follow Stress Processes

In vivo NMR of small 13C-enriched aquatic organisms is developing as a powerful tool to detect and explain toxic stress at the biochemical level. Amino acids are a very important category of metabolites for stress detection as they are involved in the vast majority of stress response pathways. As such, they are a useful proxy for stress detection in general, which could then be a trigger for more in-depth analysis of the metabolome. 1H–13C heteronuclear single quantum coherence (HSQC) is commonly used to provide additional spectral dispersion in vivo and permit metabolite assignment. While some amino acids can be assigned from HSQC, spectral overlap makes monitoring them in vivo challenging. Here, an experiment typically used to study protein structures is adapted for the selective detection of amino acids inside living Daphnia magna (water fleas). All 20 common amino acids can be selectively detected in both extracts and in vivo. By monitoring bisphenol-A exposure, the in vivo amino acid-only approach identified larger fluxes in a greater number of amino acids when compared to published works using extracts from whole organism homogenates. This suggests that amino acid-only NMR of living organisms may be a very sensitive tool in the detection of stress in vivo and is highly complementary to more traditional metabolomics-based methods. The ability of selective NMR experiments to help researchers to “look inside” living organisms and only detect specific molecules of interest is quite profound and paves the way for the future development of additional targeted experiments for in vivo research and monitoring.
Action of ear acupuncture in people with chronic pain in the spinal column: a randomized clinical trial 1

ABSTRACT Objectives: to assess the action of ear acupuncture on disability and tissue temperature in people with chronic pain in the spinal column. Method: a clinical trial with a sample of 110 people, randomized into three groups: Treatment, Placebo and Control. The assessment instruments were the Rolland Morris Disability Questionnaire (RMDQ) and a thermographic camera, administered before the first treatment session, one week after and 15 days after (follow-up) the fifth session of ear acupuncture. In the analysis of the data, the Kruskal Wallis, Student-Newman Keuls and Wilcoxon tests were applied. Results: there was a significant reduction in disability in the Treatment and Placebo groups between the initial and final assessments (p<0.05) and between the initial assessments and follow-up (p<0.05). In the final assessment, the Treatment group presented improvement of disability when compared with the Placebo and Control groups (p<0.05). There was an increase in mean tissue temperature of the dorsal region between the initial and follow-up assessments in Treatment and Control groups (p<0.05), and between the final assessments and follow-up in the Treatment and Placebo groups (p<0.05). Conclusion: ear acupuncture was efficacious in reducing disability and increasing tissue temperature in people with chronic pain in the spinal column. Brazilian Register of Clinical Trials (RBR-5X69X2).