Miracle-dz/UniFAR-FTUs huggingface dataset:
SWOG 0514: A phase II study of sorafenib (BAY 43–9006) as single agent in patients (pts) with unresectable or metastatic gallbladder cancer or cholangiocarcinomas

4639 Background: There are no standard chemotherapeutic regimens for incurable biliary adenocarcinomas. Gemcitabine and fluoropyrimidine- based chemotherapy results in occasional responses and a median survival approaching 6 months. Given the presence of b- raf mutations and overexpression of VEGF in biliary cancers, we initiated a study to evaluate the efficacy of sorafenib, a multitargeted tyrosine kinase inhibitor of c and b-Raf, VEGFR-2/3 and PDGFR, in pts with metastatic biliary cancers. Methods: Pt eligibility included adequate organ function and no prior treatment for metastatic disease. The primary end-point was objective response rate (RR). Secondary endpoints were overall survival (OS) and progression free survival (PFS). A two-stage design was used to detect a difference in the null hypothesis of 5% response probability and the alternative 20% response probability. If at least one confirmed response occurred after the first 25 pts, another 25 were to be accrued. Sorafenib was administered at 40.
Celiac disease in Saudi children with isolated short stature: is it rare or are we not screening rigorously enough?

Abstract Background Celiac disease (CeD) is an immune-mediated enteropathy induced by gluten exposure in individuals with genetic susceptibility. Short stature (SS) can be the sole clinical manifestation of CeD, in the absence of gastrointestinal (GI) symptoms. This study aimed to determine the prevalence of CeD in Saudi Arabian children with SS. Patients and methods Medical records were reviewed in a total number of 275 retrospective cases (during the period 2002–2014) of children with isolated SS from King Abdulaziz University Hospital, Jeddah. Their serum samples were tested with tissue transglutaminase (tTG) antibodies. Patients with a positive serology were scheduled for an upper endoscopy and intestinal biopsy to confirm CeD diagnosis before starting a gluten-free diet (GFD). Clinical, anthropometric and laboratory data were recorded for all patients. Results A total of 275 children with SS were included. The mean age ± standard deviation (SD) was 9.4 ± 4.0 years (range, 2.6–16.9 years) and males constituted the predominant gender group (151/275; 54.9%) over females (124/275; 45.1%). The mean ± SD height for age z score (HAZ) was −2.9 ± 1.0. Thirty-eight (13.8%) had positive serology, and 16 (5.8%) had biopsy-proven CeD. Apart from the difference in duration of delayed bone age between CeD patients and CeD-negative serology subjects (mean ± SD, 39.6 ± 10.5 vs. 18.6 ± 16.8, p = 0.02), no other major difference in other clinical or laboratory parameters was evident. Conclusions The prevalence rate of CeD in Saudi Arabian SS children was 5.8%, which is comparable to published reports of a number of other countries. Regular screening of children with SS is therefore justifiable.
Cerebrovascular Disease and Stroke

Background: Dysphagia following Stroke is very common and percutaneous endoscopic gastrostomy (PEG) tube insertion is considered as an option to help stroke patients start feeding. The aim of our study was to investigate if Specific factors could predict mortality risk in post stroke patients who had PEG tube insertion for persistent dysphagia. The FOOD trial has shown that early PEG insertion following a stroke is associated with an increase in absolute risk of death 1.0% (95% CI -10 to 11.9; p = 0.9) and increase risk of death and poor outcome 7.8% (95% CI 0.0 to 15.5; p = 0.05). Methods: This was a retrospective study of 124 patients who had PEG tube insertion following stroke who were admitted to the stroke unit at the Royal Liverpool Hospital between 2009 to 2013. Univariable Analysis was done from time to death from date of PEG insertion analyzed using Cox’s proportional hazards method. Parsimonious multivariable model was built using backwards selection with variables dropped according to Akaike’s Information Criterion. Results: Median follow-up was 6.8 years (IQR 6.0 to 7.4 years). Median event-free survival was 1.4 years (IQR: 0.7 to 1.9 years). Co-variables included age, stroke sub-type, Charlson Co-Morbidity Index (CCI), serum albumin and BMI. Survival time was strongly correlated to: increase in age, Total anterior circulation stroke (TACS), raised CCI, low serum albumin and BMI. Age was significantly associated with time to death – risk of death was 4% higher per year increase in age. Type of stroke was significantly associated with time to death – people with TACS were 65% more likely to die than those with haemorrhagic stroke. Charlson Co-Morbidity Index was significantly associated with time to death – risk of death was 15% higher per unit increase in Charlson Co-Morbidity Index.Serum albumin was significantly associated with time to death – risk of death was 5% lower per unit increase in serum albumin. BMI was significantly associated with time to death – risk of death was 5% lower per unit increase in BMI. Conclusion: This study demonstrates a clear prognostic value of these co-variables with patients worked up for PEG insertion after stroke. Interesting find was that a combination of TACS stroke, Age >80, Albumin <30g/L, CCI >=9 and low BMI in Men had probability of upto >80 % 6 month mortality after PEG insertion. We propose that Further Multicenter research is required to determine a predictive algorithm to be used in future guidelines and management of PEG-based decisions in stroke.
The effect of intraperitoneal local anaesthetic in colonic surgery

II DEDICATION . III ACKNOWLEDGMENTS . IV PUBLICATIONS AND CONFERENCE PRESENTATIONS . VI TABLE OF CONTENTS . IX LIST OF TABLES . XII LIST OF FIGURES . XIV GLOSSARY . XVII CHAPTER 1 : INTRODUCTION . 1 CHAPTER 2 : LITERATURE REVIEW . 4 2.1. 1 Stress . 6 2.1. 2 Stimuli . 7 2.2.1 Organ dysfunction . 9 2.2.2 PSF, prolonged convalescence and functional deficit . 11 2.3.1 The Somatic Wound . 17 2.3.2 The Autonomic Wound . 19 2.4. 1 Multimodal rehabilitation . 29 2.4. 2 Pharmaco-therapeutics . 35 2.4. 3 Local anaesthetic drugs . 38 CHAPTER 3 : SYSTEMATIC REVIEW OF IPLA. 44 3.1. 1 Aims and objectives . 46 3.1. 2 Search strategy . 46 3.1. 3 Study selection . 47 3.1. 4 Study methodological assessment . 47 3.2.1 Open abdominal procedures . 53 3.2.2 Laparoscopic cholecystectomy . 60 3.2.3 Laparoscopic (non-cholecystectomy) Surgery . 77 3.3.1 Mechanism of action . 82 3.3.2 Future research . 85 2.1 Definitions . 6 2.2 The Post-operative state . 9 2.3 One patient, two wounds . 16 2.4 Current interventions . 28 2.5 Chapter Summary . 42 3.1 Methods . 46 3.2 Results . 51 3.3 Discussion . 81 3.4 Chapter Summary . 87
Observational non-randomised controlled evaluation of the effectiveness of cancer counselling centres: a study protocol

Introduction In recent years, medical treatment for cancer has improved, thereby increasing the life expectancy of patients with cancer. Hence, the focus in healthcare shifted towards analysing treatments that offer to decrease distress and improve the quality of life of patients with cancer. The psychological burden of patients with cancer originates from all kinds of psychosocial challenges related to diagnosis and treatment. Cancer counselling centres (CCounCs) try to address these concerns. However, the current literature lacks research on the effectiveness of CCounCs. This study aims to assess the effectiveness of CCounCs with regard to distress and other relevant psychosocial variables (quality of life, anxietyand so on). Methods and analysis This prospective observational study with a non-randomised control group has three measurement points: before the first counselling session (baseline, t0) and at 2 weeks and 3 months after baseline (t1, t2). Patients and their relatives who seek counselling between December 2018 and November 2020 and have sufficient German language skills will be included. The control group will be recruited at clinics and oncological outpatient centres in Hamburg. Propensity scoring will be applied to adjust for differences between the control and intervention groups at baseline. Sociodemographic data, medical data and counselling concerns are measured at baseline. Distress (distress thermometer), quality of life (Short Form-8 Health Survey, European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire-Core 30), anxiety (Generalized AnxietyDisorder-7), depression (Patient HealthQuestionnaire-9) and further psychosocial variables are assessed at all time points. With a total of 787 participants, differences between the intervention and control groups of a small effect size (f=0.10) can be detected with a power of 80%. Ethics and dissemination The study was registered prior to data collection with the German Registration of Clinical Trials in September 2018. Ethical approval was received by the local psychological ethical committee of the Center for Psychosocial Medicine at the University Medical Centre Hamburg-Eppendorf in August 2018. The results will be published in peer-reviewed journals. Trial registration number DRKS00015516; Pre-results.
An investigation of the equine epidermal growth factor system during hyperinsulinemic laminitis

Equine laminitis is a disease of the digital epidermal lamellae typified by epidermal cell proliferation and structural collapse. Most commonly the disease is caused by hyperinsulinemia, although the pathogenesis is incompletely understood. Insulin can activate the epidermal growth factor (EGF) system in other species and the present study tested the hypothesis that upregulation of EGF receptor (EGFR) signalling is a key factor in laminitis pathophysiology. First, we examined lamellar tissue from healthy Standardbred horses and those with induced hyperinsulinemia and laminitis for EGFR distribution and quantity using immunostaining and gene expression, respectively. Phosphorylation of EGFR was also quantified. Next, plasma EGF concentrations were compared in healthy and insulin-infused horses, and in healthy and insulin-dysregulated ponies before and after feeding. The EGFR were localised to the secondary epidermal lamellae, with stronger staining in parabasal, rather than basal, cells. No change in EGFR gene expression occurred with laminitis, although the receptor showed some phosphorylation. No difference was seen in EGF concentrations in horses, but in insulin-dysregulated ponies mean, post-prandial EGF concentrations were almost three times higher than in healthy ponies (274 ± 90 vs. 97.4 ± 20.9 pg/mL, P = 0.05). Although the EGFR does not appear to play a major pathogenic role in hyperinsulinemic laminitis, the significance of increased EGF in insulin-dysregulated ponies deserves further investigation.
Real-world effectiveness of smoking cessation strategies for young and older adults: Findings from a nationally representative cohort.

INTRODUCTION Young adults have high combustible cigarette and e-cigarette use rates, and low utilization of evidence-based smoking cessation strategies compared to older adults. It is unknown whether young adults who try to quit smoking without assistance, with evidence-based strategies, or with e-cigarettes, are equally successful compared to older adults. METHODS This analysis used a population-based sample from the Population Assessment of Tobacco and Health (PATH) Study of young adult (aged 18-24, n=745) and older adult (aged 25-64, n=2,057) established cigarette smokers at Wave 1 (2013-2014) who reported having made a quit attempt at Wave 2 (2014-2015). Cessation strategies were: behavioral therapy, pharmacotherapy, product substitution, 2+ strategies, and unassisted. Logistic regression estimated associations between cessation strategy and short-term cessation status at Wave 2 (quit, no quit); multinomial logistic regression predicted long-term cessation patterns at Waves 2 and 3 (sustained quit, temporary quit, delayed quit, no quit). RESULTS No cessation strategy (ref: unassisted) significantly predicted short-term cessation. No cessation strategy (ref: unassisted) significantly predicted long-term cessation patterns for young adults. Substitution with e-cigarettes predicted short-term cessation for older daily smokers of ≥ 5 cigarettes/day (AOR: 1.70; 95% CI: 1.08, 2.67) but did not predict long-term cessation patterns. CONCLUSIONS Despite differences in cessation strategy use between young and older adult smokers, strategy effectiveness largely did not differ by age group. No strategy examined, including e-cigarettes, was significantly associated with successful cessation for young adults. More work is needed to identify effective interventions that help young adult smokers quit. IMPLICATIONS Neither behavioral support, pharmacotherapy, nor product substitution was associated with short-term cessation for young or older adults compared to quitting unassisted.Neither behavioral support, pharmacotherapy, nor product substitution was associated with longer-term cessation for young or older adults compared to quitting unassisted.Substitution with e-cigarettes predicted short-term cessation for older daily smokers of ≥ 5 cigarettes/day but was not associated with longer-term cessation.
Key stakeholders and their perceptions of the current position and viability of independent prep schools

The current educational position and viability of the standalone preparatory (prep) school in England is examined through the perceptions of three sets of key stakeholders: parents, prep Heads, and senior school Heads. This type of school has been in existence for centuries and today forms a unique part of the independent education sector, but it is believed to be under threat due to declining numbers and school closures. The research used purposive and convenience sampling to identify case studies and face-to-face interviews were conducted with the key stakeholders. The case studies were selected from the Greater London area (deemed urban) and the Rest of England (deemed rural). Parents and Heads from eight prep schools and six senior schools were interviewed. The key stakeholders expressed their views with regard to the benefits (or otherwise) of prep schools and the pupils educated in them, the clients and the competition of such establishments. The study examines the issues currently facing the prep school as identified by the key stakeholders and considers whether these issues pose a potential threat to the sector’s viability. These risks are also considered in comparison to some broader trends affecting the education market in general. The research highlighted a large number of similarities across stakeholder views across geographical locations and noted the emergence of a new type of client. A second strand to the London market was identified which had a different purpose behind their choosing of a prep school. While no single threat is likely to be fatal to the prep school, a number of threats have appeared which, in combination risk a long, slow demise of this type of school. Although pupil numbers have plateaued over recent years, the emergence of the new customer, together with a willingness to adapt and to address at least some of the threats being faced, could be enough to ensure the survival of prep schools. However evidence of tension between education and the market was evident and could in itself impact on such a school.
Report of seven cases and review of the literature

v" Seven cases of pituitary abscess are presented and the relevant world literature is reviewed. An enlarged sella co-existing with bacterial meningitis, or bacterial meningitis coinciding with a known or suspected pituitary tumor should suggest the diagnosis of pituitary abscess. Visual field defects should evoke similar suspicion when present in a patient with meningitis. This reasoning enabled us to make the first reported preoperative diagnosis of pituitary abscess. Therefore, in the management of purulent meningitis, we recommend the following: first, skull films are mandatory; second, if the sella turcica is abnormal, the correct presumptive diagnosis is pituitary abscess; and third, if prompt improvement does not follow appropriate antibiotic therapy, the suspected abscess should be explored and drained via the transsphenoidal approach.
Fatty acid profile of milk

Quality, processing ability and sensory properties of milk are highly correlated with content and composition of milk fat. Biologically active lipid substances are primarily saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs; linoleic acid; C18:2 n-6) and polyunsaturated fatty acids (PUFAs; α-linolenic acid; C18:3 n-3). PUFAs with 20C, mainly docosahexaenoic acid (DHA; C20:5 n-3) and eicosapentaenoic acid (EPA; SC22:6 n-3), are precursors of eicosanoids, which regulate various physiological processes. Fatty acid composition depends on many different factors, such as animal species, breed, season, lactation stage, geographical location, and diet. Goat and sheep milk are rich in the medium chain fatty acids, caproic (C6:0), caprylic (C8:0) and capric (C10:0), which is the reason for the specific aroma of those kinds of milk. Goat and sheep milk have more conjugated linoleic acid, and usually lower n-6/n-3 ratios, with higher amounts of α-linolenic acid, compared to cow milk. Compared to goat and cow milk, sheep milk has the lowest amounts of lauric (C12:0), myristic (C14:0) and palmitic (C16:0) acids i.e. fatty acids associated with negative effects on human health. The addition of forage, especially fresh grass, to dairy animal diets enhances the proportion of unsaturated fatty acids in milk fat compared to SFAs and increases the amount of conjugated linoleic acid.
ASSESSMENT OF THE RISK OF DEFICIENCY IN POPULATIONS AND OPTIONS FOR ITS CONTROL

Chapter 1: Overview of Zinc Nutrition S99 1.1 Biological functions of zinc S99 1.2 Tissue zinc distribution and reserves S99 1.3 Zinc metabolism S100 1.4 Importance of zinc for human health S101 1.5 Human zinc requirements S105 1.5. 1 Adult men S106 1.5. 2 Adult women S109 1.5. 3 Children S110 1.5. 4 Pregnancy S111 1.5. 5 Lactation S112 1.6 Dietary sources of zinc and suggested revisions of Recommended Daily Intakes S112 1.6. 1 Dietary sources of zinc and factors affecting the proportion of zinc available for absorption . S112 1.6. 2 Revised estimates of dietary requirements and recommended intakes for zinc S114 1.7 Zinc toxicity S118 1.8 Causes of zinc deficiency and groups at high risk S121 1.9 Summary S123
Identification of p62 as interaction partner of ARTD9: is ARTD9 degraded by autophagy?

Das B-aggressive Lymphomprotein (BAL1/ARTD9) wurde als prognostischen Marker fur den Verlauf von diffus grosszelligem B-Zell Lymphom identifiziert, dem meistdiagnostizierten Lymphom bei Erwachsenen. Als macroARTD enthalt ARTD9 zwei macro Domanen und eine ADP-ribosyltransferasen-Domane, und gehort somit zu den diphterietoxin-ahnlichen ADP- ribosyltransferasen (ARTDs). Ziel dieser Arbeit war es, Interaktionspartner von macroARTD Proteinen zu identifizieren und funktionell zu charakterisieren. Unter Verwendung eines unvoreingenommenen Immunprazipitationsverfahrens und mit Hilfe von Glutathion S- Transferase (GST) Pulldowns wurden Interaktionspartner der gesamtprotein- als auch der macro-Domanen-spezifischen BAL-Komplexe unter physiologischen Bedingungen untersucht. Anschliessend wurden interagierende Proteine mit Massenspektrometrie identifiziert und mittels Westernblot validiert. Das Protein p62, das an der selektiven Autophagie zentral beteiligt ist, wurde als spezifischer Interaktionspartner der ARTD9 macro Domanen gefunden. p62 ist in mehreren menschlichen Tumoren hochreguliert. Daher wurde der Effekt induzierter Autophagie auf ARTD9 untersucht. Wir stellten fest, dass die Menge an ARTD9 abnimmt, wenn Autophagie durch Hungern in A549 Zellen ausgelost wird. Dieser Effekt konnte mit p62 siRNA aufgehoben werden, jedoch nicht mit beclin-1 siRNA. Diese Resultate zeigen, dass ARTD9 durch p62-abhangige aber beclin-1 unabhangige selektive Autophagie abgebaut wird. B-aggressive lymphoma 1 protein (BAL1/ARTD9) was described as prognostic marker for the progression of diffuse large B-cell lymphoma, the most common lymphoid cancer in humans. As a macroARTD, BAL1/ARTD9 contains 2 macro and an ADP-ribosyltransferase domain, the signature of diphteria toxin-like ADP-ribosyltransferases (ARTDs). The aim of this study was to identify and functionally characterize interaction partners of the macroARTD proteins. Using an unbiased glutathione S-transferase (GST) pull-down and co- immunoprecipitation approach, full length and macro domain specific interaction partners of BAL complexes were investigated under physiological conditions. Subsequently, protein interaction partners were identified by mass spectrometry and validated by western blot. Among other proteins, p62, a signaling hub involved in selective autophagy, was found as specific interaction partner of the ARTD9 macro domains. p62 is up-regulated in several human tumors. Therefore the effect of autophagy induction on ARTD9 was investigated. We discovered that ARTD9 levels are decreased upon induction of autophagy by starvation in A549 cells. is effect was abolished by p62 but not beclin-1 siRNA. These results revealed that ARTD9 is degraded by p62 dependent but beclin-1 independent selective autophagy.
Does current thyroid cancer staging accurately reflect the impact of lymph node metastases on survival in younger patients

Department of Surgery, Duke University Medical Center, DUMC 3704, Durham, NC 27710, USA Duke Clinical Research Institute, 2400 Pratt St, Durham, NC 27705, USA *Author for correspondence: Tel. : +1 919 668 1767; Fax: +1 919 684 6044; Julie.sosa@duke.edu