LLukas22/scidocs huggingface dataset:
Adjuvant endocrine treatment (goserelin vs tamoxifen) in pre-menopausal patients with operable node positive stage II breast cancer. A prospective randomized national multicenter study.

AIMS
To evaluate possible differences in effect on time to recurrence and overall survival in node positive pre-menopausal breast cancer patients (age < or = 50 years) receiving LHRH analogue or tamoxifen as adjuvant endocrine treatment.


METHODS
Between January 1989 and July 1994, 320 patients with node positive (pN(+)) and hormone receptor positive or receptor status unknown tumors were included and randomized in a national multicenter study to receive either tamoxifen or goserelin as adjuvant treatment for two years. Primary surgical treatment was employed according to current standards. Final follow-up was completed as of December 2000. Time to events were estimated by the Kaplan-Meier method, and compared by the log rank test. Relative risks were estimated by the Cox's proportional hazards model.


RESULTS
No differences in time to first recurrence or overall survival were observed between treatment groups. Proportions of patients in each group having a second breast cancer were also similar.


CONCLUSIONS
Standard adjuvant treatment with tamoxifen as compared to adjuvant LHRH analogue therapy employed in this group of breast cancer patients gave similar outcomes, but the number of patients was too small to formally exclude a potentially clinically relevant difference in survival.
Improving protein disorder prediction by deep bidirectional long short-term memory recurrent neural networks

Motivation
Capturing long-range interactions between structural but not sequence neighbors of proteins is a long-standing challenging problem in bioinformatics. Recently, long short-term memory (LSTM) networks have significantly improved the accuracy of speech and image classification problems by remembering useful past information in long sequential events. Here, we have implemented deep bidirectional LSTM recurrent neural networks in the problem of protein intrinsic disorder prediction.


Results
The new method, named SPOT-Disorder, has steadily improved over a similar method using a traditional, window-based neural network (SPINE-D) in all datasets tested without separate training on short and long disordered regions. Independent tests on four other datasets including the datasets from critical assessment of structure prediction (CASP) techniques and >10 000 annotated proteins from MobiDB, confirmed SPOT-Disorder as one of the best methods in disorder prediction. Moreover, initial studies indicate that the method is more accurate in predicting functional sites in disordered regions. These results highlight the usefulness combining LSTM with deep bidirectional recurrent neural networks in capturing non-local, long-range interactions for bioinformatics applications.


Availability and Implementation
SPOT-disorder is available as a web server and as a standalone program at: http://sparks-lab.org/server/SPOT-disorder/index.php .


Contact
j.hanson@griffith.edu.au or yuedong.yang@griffith.edu.au or yaoqi.zhou@griffith.edu.au.


Supplementary information
Supplementary data is available at Bioinformatics online.
Role of hepatic vein catheterisation and transient elastography in the diagnosis of idiopathic portal hypertension.

BACKGROUND
Idiopathic portal hypertension is a rare cause of portal hypertension, frequently misdiagnosed as cryptogenic cirrhosis. This study evaluates specific findings at hepatic vein catheterisation or liver stiffness in idiopathic portal hypertension.


METHODS
39 cases of idiopathic portal hypertension patients were retrospectively reviewed. Hepatic vein catheterisation and liver stiffness measurements were compared to matched patients with cirrhosis and portal hypertension, and non-cirrhotic portal vein thrombosis, included as controls.


RESULTS
Hepatic vein-to-vein communications were found in 49% idiopathic portal hypertension patients precluding adequate hepatic venous pressure gradient measurements in 12. In the remaining 27 patients, mean hepatic venous pressure gradient (HVPG) was 7.1 ± 3.1 mm Hg. Only 5 patients had HVPG≥10mmHg. HVPG was markedly lower than in cirrhosis (17 ± 3 mm Hg, p<0.001). Mean liver stiffness in idiopathic portal hypertension was 8.4 ± 3.3 kPa; significantly higher than in non-cirrhotic portal vein thrombosis (6.4 ± 2.2 kPa, p=0.009), but lower than in cirrhosis (40.9 ± 20.5 kPa, p=0.005). Only 2 idiopathic portal hypertension patients had liver stiffness >13.6 kPa.


CONCLUSIONS
Patients with idiopathic portal hypertension frequently have hepatic vein-to-vein communications and, despite unequivocal signs of portal hypertension, HVPG and liver stiffness values much lower than the cut-off for clinical significant portal hypertension in cirrhosis. These findings oblige to formally rule-out idiopathic portal hypertension in the presence of signs of portal hypertension.
Modeling of Cutting Forces Under Hard Turning Conditions Considering Tool Wear Effect

Quantitative understanding of cutting forces under hard turning conditions is impor for thermal modeling, tool life estimation, chatter prediction, and tool condition moni ing purposes. Although significant research has been documented on the model forces in the turning operation in general, turning of hardened materials involves sev distinctive process conditions, including negative tool rake angle, large tool nose ra and rapid tool wear. These process conditions warrant specific treatment in the analy cutting forces. This paper first addresses these issues by formulating an oblique formation force model through the extension of a two-dimensional (2D) mechanistic model while considering the effect of tool geometry complexities. The coefficients mechanistic force model are estimated by applying a genetic algorithm in overcomin lack of explicit normal equations. Then the forces occurring due to flank wear are m eled by extending a 2D worn tool force modeling approach into a three-dimensi analysis to accommodate the effect of low feed rate, small depth of cut, and rela large tool nose radius in hard turning. The total cutting forces are the linear summa of forces due to chip formation and forces due to flank wear. The model-predicted f match well with experimental results in the turning of hardened 52100 bearing steel u practical cutting conditions (low feed rate, small depth of cut, and gentle cutting sp using cubic boron nitride (CBN) tools under the progressive tool flank wear conditio @DOI: 10.1115/1.1852571 #
Salmonella enterica: living a double life in epithelial cells.

Intracellular bacterial pathogens can occupy a membrane-bound vacuole or live freely within the cytosol of mammalian cells. Many studies have shown that the enteric bacterium, Salmonella enterica serovar Typhimurium (S. Typhimurium), is a vacuolar pathogen. Recent data, however, have revealed that within epithelial cells there are subpopulations of vacuolar and cytosolic Salmonella. Release from the Salmonella-containing vacuole leads to transcriptional reprogramming of bacteria and their robust replication in the cytosol. Eventually, epithelial cell death via pyroptosis results in cell lysis, proinflammatory cytokine release and escape of the cytosolic bacteria into the extracellular space, providing a potential mechanism of dissemination. This review focuses on the current understanding of this newly described intracellular population of Salmonella.
Formulation and Solid State Characterization of Nicotinamide-based Co-crystals of Fenofibrate

The present investigation deals with formulation of nicotinamide-based co-crystals of fenofibrate by different methods and solid-state characterization of the prepared co-crystals. Fenofibrate and nicotinamide as a coformer in 1:1 molar ratio were used to formulate molecular complexes by kneading, solution crystallization, antisolvent addition and solvent drop grinding methods. The prepared molecular complexes were characterized by powder X-ray diffractometry, differential scanning calorimetry, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy and in vitro dissolution study. Considerable improvement in the dissolution rate of fenofibrate from optimized co-crystal formulation was due to an increased solubility that is attributed to the super saturation from the fine co-crystals is faster because of large specific surface area of small particles and prevention of phase transformation to pure fenofibrate. In vitro dissolution study showed that the formation of co-crystals improves the dissolution rate of fenofibrate. Nicotinamide forms the co-crystals with fenofibrate, theoretically and practically.
When Firmware Modifications Attack: A Case Study of Embedded Exploitation

The ability to update firmware is a feature that is found in nearly all modern embedded systems. We demonstrate how this feature can be exploited to allow attackers to inject malicious firmware modifications into vulnerable embedded devices. We discuss techniques for exploiting such vulnerable functionality and the implementation of a proof of concept printer malware capable of network reconnaissance, data exfiltration and propagation to general purpose computers and other embedded device types. We present a case study of the HP-RFU (Remote Firmware Update) LaserJet printer firmware modification vulnerability, which allows arbitrary injection of malware into the printer’s firmware via standard printed documents. We show vulnerable population data gathered by continuously tracking all publicly accessible printers discovered through an exhaustive scan of IPv4 space. To show that firmware update signing is not the panacea of embedded defense, we present an analysis of known vulnerabilities found in third-party libraries in 373 LaserJet firmware images. Prior research has shown that the design flaws and vulnerabilities presented in this paper are found in other modern embedded systems. Thus, the exploitation techniques presented in this paper can be generalized to compromise other embedded systems. Keywords-Embedded system exploitation; Firmware modification attack; Embedded system rootkit; HP-RFU vulnerability.
Regional Redistribution Through the U.S. Mortgage Market

Regional shocks are an important feature of the U.S. economy. Households’ ability to self-insure against these shocks depends on how they affect local interest rates. In the United States, most borrowing occurs through the mortgage market and is influenced by the presence of governmentsponsored enterprises (GSEs). We establish that despite large regional variation in predictable default risk, GSE mortgage rates for otherwise identical loans do not vary spatially. In contrast, the private market does set interest rates that vary with local risk. We use a spatial model of collateralized borrowing to show that the national interest rate policy substantially affects welfare by redistributing resources across regions. ∗First draft: April 2014. We thank Sumit Agarwal, Heitor Almeida, Tom Davidoff, John Driscoll, Matthew Kahn, Arvind Krishnamurthy, John Leahy, Tomasz Piskorski, Stijn Van Nieuwerburgh, Monika Piazzesi, David Scharfstein, Johannes Stroebel, Adi Sunderam, Francesco Trebbi, and seminar participants at Berkeley Haas, Ennaudi Institute, Federal Reserve Board, HEC, Indian School of Business, Kellogg, MIT, National University of Singapore, NBER Monetary Economics Program Meeting, Ohio State, NBER Summer Institute, Chicago Fed, Rutgers, Stanford, Toronto, UBC, UCLA, University of Chicago Booth, University of Chicago Harris, University of Illinois, University of Michigan, Wharton, the FRIC 2014 conference on financial frictions, and the NBER conference on Financing Housing Capital for helpful comments and suggestions. Any remaining errors are our own. E-mail: Erik.Hurst@chicagobooth.edu; benkeys@uchicago.edu; Amit.Seru@chicagobooth.edu; Joseph.Vavra@chicagobooth.edu.
Effects on motor development of kicking and stepping exercise in preterm infants with periventricular brain injury: a pilot study.

BACKGROUND
Preterm infants with periventricular brain injury (PBI) have a high incidence of atypical development and leg movements.


OBJECTIVE
Determine whether kicking and treadmill stepping intervention beginning at 2 months corrected age (CA) in children with PBI improves motor function at 12 months CA when compared with control subjects.


METHOD
In a multi-center pilot study for a controlled clinical trial, sixteen infants with PBI were randomly assigned to home exercise consisting of kicking and treadmill stepping or a no-training control condition. Development was assessed at 2, 4, 6, 10, and 12 months CA with the Alberta Infant Motor Scale (AIMS). At 12 months children were classified as normal, delayed, or with cerebral palsy (CP).


RESULTS
At 12 months CA 3 of 7 (43%) of the exercise group children walked alone or with one hand held versus 1 of 9 (11%) in the control group (p=0.262), but no significant differences in AIMS scores were found at any age. Half of the subjects had CP or delay; the outcomes of these infants were not improved by exercise. Compliance with the home program was lower than requested and may have affected results.


CONCLUSION
Although not statistically significant with a small sample size, self-produced kicking and treadmill exercise may lower age at walking in infants with normal development following PBI, but improvements of the protocol to increase and document compliance are needed before a larger study is implemented.
Copper localization in Cannabis sativa L. grown in a copper-rich solution

With the aim to examine its potential as a renewable resource to decontaminate polluted soils, electron microscopy combined with X-ray microanalysis was used to investigate the localization of copper in Cannabis sativa grown in hydroponic copper-rich culture. Cu was found to accumulate preferentially in the upper leaf epidermal cells; it was also detected in spiculae and in abaxial trichomes too. Primary bast fibres seem to be not involved in copper accumulation.
Consequences of radial artery harvest: results of a prospective, randomized, multicenter trial.

IMPORTANCE
To date, no study has defined the consequences of radial artery harvest based on a large number of patients in a prospective randomized trial.


OBJECTIVE
To compare pain at the harvest site and functional changes associated with harvesting the radial artery vs saphenous vein for coronary artery bypass grafting.


DESIGN, SETTING, AND PARTICIPANTS
This study compares the consequences of radial artery harvest with saphenous vein harvest in patients undergoing elective coronary artery bypass grafting procedures in Veterans Affairs hospitals.


MAIN OUTCOMES AND MEASURES
Eleven hospitals screened 6148 patients, of whom 751 were included in this trial. We analyzed 2 variables: pain at the harvest site as measured on a scale of 0 to 100 (least to most painful) and hand performance testing. Patients included in this analysis had radial artery only (n = 80) or saphenous vein only (n = 337) harvest. Pain score, grip strength, and dexterity were measured before surgery and at 3 and 12 months after surgery. We adjusted for pain scores of the nonharvested extremity, age, whether the patient underwent endoscopic vein harvesting, and comorbid health conditions (smoking history, type 2 diabetes mellitus, hypertension, and heart failure).


RESULTS
There was a significant difference in change of pain score at 3 months from the preoperative baseline between radial artery and saphenous vein groups after adjusting for covariates (P < .001) but not at 12 months (P = .07). No significant changes occurred in grip strength or dexterity from preoperative baseline to 3 and 12 months after surgery (P > .05).


CONCLUSIONS AND RELEVANCE
The radial artery group reported significantly more pain than the saphenous vein group 3 months after surgery; however, similar levels of pain were observed in both groups at 12 months after surgery. Grip strength and manual dexterity were not changed by radial artery harvesting at 3 and 12 months.
Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety?

BACKGROUND
For the past 30 years, opioids have been used to treat chronic nonmalignant pain. This study tests the following hypotheses: (1) there is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective; and (2) the main problem associated with the safety of such treatment - assessment of the risk of addiction - has been neglected.


METHODS
Scientometric analysis of the articles representing clinical research in this area was performed to assess (1) the quality of presented evidence (type of study); and (2) the duration of the treatment phase. The sufficiency of representation of addiction was assessed by counting the number of articles that represent (1) editorials; (2) articles in the top specialty journals; and (3) articles with titles clearly indicating that the addiction-related safety is involved (topic-in-title articles).


RESULTS
Not a single randomized controlled trial with opioid treatment lasting >3 months was found. All studies with a duration of opioid treatment ≥6 months (n = 16) were conducted without a proper control group. Such studies cannot provide the consistent good-quality evidence necessary for a strong clinical recommendation. There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general. An inadequate number of chronic pain-related publications were observed with all three types of counted articles: editorials, articles in the top specialty journals, and topic-in-title articles.


CONCLUSION
There is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective. The above identified signs indicating neglect of addiction associated with the opioid treatment of chronic nonmalignant pain were present.
Opioid analgesia: perspectives on right use and utility.

The ability of opioids to effectively and safely control acute and cancer pain has been one of several arguments used to support extending opioid treatment to patients with chronic pain, against a backdrop of considerable caution that has been based upon fears of addiction. Of course, opioids may cause addiction, but the "principle of balance" may justify that "...efforts to address abuse should not interfere with legitimate medical practice and patient care." Yet, situations are increasingly encountered in which opioid-maintained patients are refractory to analgesia during periods of pain, or even during the course of chronic treatment. The real question is whether analgesic efficacy of opioids can be maintained over time. Overall, the evidence supporting long-term analgesic efficacy is weak. The putative mechanisms for failed opioid analgesia may be related to tolerance or opioid-induced hyperalgesia. Advances in basic sciences may help in understanding these phenomena, but the question of whether long-term opioid treatment can improve patients' function or quality of life remains a broader issue. Opioid side effects are well known, but with chronic use, most (except constipation) subside. Still, side effects can negatively affect the outcomes and continuity of therapy. This paper addresses 1) what evidence supports the long-term utility of opioids for chronic pain; 2) how side effects may alter quality of life; 3) the nature of addiction and why it is different in pain patients, and 4) on what grounds could pain medication be denied? These questions are discussed in light of patients' rights, and warrant balancing particular responsibilities with risks. These are framed within the Hippocratic tradition of "producing good for the patient and protecting from harm," so as to enable 1) more informed clinical decision making, and 2) progress towards right use and utility of opioid treatment for chronic pain.
Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial

BACKGROUND
The non-nucleoside reverse transcriptase inhibitor (NNRTI), rilpivirine (TMC278; Tibotec Pharmaceuticals, County Cork, Ireland), had equivalent sustained efficacy to efavirenz in a phase 2b trial in treatment-naive patients infected with HIV-1, but fewer adverse events. We aimed to assess non-inferiority of rilpivirine to efavirenz in a phase 3 trial with common background nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs).


METHODS
We undertook a 96-week, phase 3, randomised, double-blind, double-dummy, non-inferiority trial in 98 hospitals or medical centres in 21 countries. We enrolled adults (≥18 years) not previously given antiretroviral therapy and with a screening plasma viral load of 5000 copies per mL or more and viral sensitivity to background N(t)RTIs. We randomly allocated patients (1:1) using a computer-generated interactive web-response system to receive oral rilpivirine 25 mg once daily or efavirenz 600 mg once daily; all patients received an investigator-selected regimen of background N(t)RTIs (tenofovir-disoproxil-fumarate plus emtricitabine, zidovudine plus lamivudine, or abacavir plus lamivudine). The primary outcome was non-inferiority (12% margin on logistic regression analysis) at 48 weeks in terms of confirmed response (viral load <50 copies per mL, defined by the intent-to-treat time to loss of virologic response [TLOVR] algorithm) in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00543725.


FINDINGS
From May 22, 2008, we screened 947 patients and enrolled 340 to each group. 86% of patients (291 of 340) who received at least one dose of rilpivirine responded, compared with 82% of patients (276 of 338) who received at least one dose of efavirenz (difference 3.5% [95% CI -1.7 to 8.8]; p(non-inferiority)<0.0001). Increases in CD4 cell counts were much the same between groups. 7% of patients (24 of 340) receiving rilpivirine had a virological failure compared with 5% of patients (18 of 338) receiving efavirenz. 4% of patients (15) in the rilpivirine group and 7% (25) in the efavirenz group discontinued treatment due to adverse events. Grade 2-4 treatment-related adverse events were less common with rilpivirine (16% [54 patients]) than they were with efavirenz (31% [104]; p<0.0001), as were rash and dizziness (p<0.0001 for both) and increases in lipid levels were significantly lower with rilpivirine than they were with efavirenz (p<0.0001).


INTERPRETATION
Despite a slightly increased incidence of virological failures, a favourable safety profile and non-inferior efficacy compared with efavirenz means that rilpivirine could be a new treatment option for treatment-naive patients infected with HIV-1.


FUNDING
Tibotec.