Miracle-dz/UniFAR-FTUs huggingface dataset:
New Brush-Type Chiral Stationary Phases for Enantioseparation of Pharmaceutical Drugs

The importance of chirality in drug development is unquestionable, with chiral liquid chromatography (LC) being the most adequate technique for its analysis. Among the various types of chiral stationary phases (CSPs) for LC, brush-type CSPs provide the base for interaction analysis of CSPs and enantiomers, which provide valuable results that can be applied to interaction studies of other CSP types. In order to analyze the influence of aromatic interactions in chiral recognition, we designed a set of ten new brush-type CSPs based on (S)-N-(1-aryl-propyl)-3,5-dinitrobenzamides which differ in the aromatic unit directly linked to the chiral center. Thirty diverse racemates, including several nonsteroidal anti-inflammatory drugs and 3-hydroxybenzodiazepine drugs, were used to evaluate the prepared CSPs. Chromatographic analysis showed that the three new CSPs separate enantiomers of a wide range of compounds and their chromatographic behavior is comparable to the most versatile brush-type CSP—Whelk-O1. The critical role of the nonbonding interactions in positioning of the analyte (naproxen) in the cleft of CSP-6, as well as the analysis of interactions that make enantioseparation possible, were elucidated using computational methods. Furthermore, the influence of acetic acid as a mobile phase additive, on this enantiorecognition process was corroborated by calculations.
Life is sweet: the cell biology of glycoconjugates

Cells are dazzling in their diversity, both within and across organisms. And yet, throughout this variety runs at least one common thread: sugars. All cells on Earth, in all domains of life, are literally covered in glycans, a term referring to the carbohydrate portion of glycoproteins and glycolipids. In spite of (or, perhaps, because of) their tremendous structural and functional complexity, glycans have historically been underexplored compared with other areas of cell biology. Recently, however, advances in experimental systems and analytical methods have ushered in a renaissance in glycobiology, the study of the biosynthesis, structures, interactions, functions, and evolution of glycans. Today, glycobiology is poised to make major new contributions to cell biology and become more fully integrated into our understanding of cell and organismal physiology.
Collision Attacks on AES-192/256, Crypton-192/256, mCrypton-96/128, and Anubis

At AES’00, a collision attack on 7-round reduced AES was proposed. In this paper, we apply this idea to seven SPN block ciphers, AES-192/256, Crypton-192/256, mCrypton-96/128, and Anubis. Applying our attacks on AES-192/256, we improve the attack result based on meet-in-the-middle attack (AES-192) and the attack result proposed in AES’00 (AES-256), respectively. Our attack result on Anubis is superior to known cryptanalytic result on it. In the cases of Crypton-192/256 and mCrypton-96/128, our attacks are applicable to 8-round reduced versions. The attack results on mCrypton-96/128 are more practical than known cryptanalytic results on them.
S3ORAM: A Computation-Efficient and Constant Client Bandwidth Blowup ORAM with Shamir Secret Sharing

Oblivious Random Access Machine (ORAM) enables a client to access her data without leaking her access patterns. Existing client-efficient ORAMs either achieve O(log N) client-server communication blowup without heavy computation, or O(1) blowup but with expensive homomorphic encryptions. It has been shown that O(log N) bandwidth blowup might not be practical for certain applications, while schemes with O(1) communication blowup incur even more delay due to costly homomorphic operations. In this paper, we propose a new distributed ORAM scheme referred to as Shamir Secret Sharing ORAM (S3ORAM), which achieves O(1) client-server bandwidth blowup and O(1) blocks of client storage without relying on costly partial homomorphic encryptions. S3ORAM harnesses Shamir Secret Sharing, tree-based ORAM structure and a secure multi-party multiplication protocol to eliminate costly homomorphic operations and, therefore, achieves O(1) client-server bandwidth blowup with a high computational efficiency. We conducted comprehensive experiments to assess the performance of S3ORAM and its counterparts on actual cloud environments, and showed that S3ORAM achieves three orders of magnitude lower end-to-end delay compared to alternatives with O(1) client communication blowup (Onion-ORAM), while it is one order of magnitude faster than Path-ORAM for a network with a moderate bandwidth quality. We have released the implementation of S3ORAM for further improvement and adaptation.
Attention bias to reward predicts behavioral problems and moderates early risk to externalizing and attention problems

Abstract The current study had three goals. First, we replicated recent evidence that suggests a concurrent relation between attention bias to reward and externalizing and attention problems at age 7. Second, we extended these findings by examining the relations between attention and behavioral measures of early exuberance (3 years), early effortful control (4 years), and concurrent effortful control (7 years), as well as later behavioral problems (9 years). Third, we evaluated the role of attention to reward in the longitudinal pathways between early exuberance and early effortful control to predict externalizing and attention problems. Results revealed that attention bias to reward was associated concurrently and longitudinally with behavioral problems. Moreover, greater reward bias was concurrently associated with lower levels of parent-reported effortful control. Finally, attention bias to reward moderated the longitudinal relations between early risk factors for behavioral problems (gender, exuberance, and effortful control) and later externalizing and attention problems, such that these early risk factors were most predictive of behavioral problems for males with a large attention bias to reward. These findings suggest that attention bias to reward may act as a moderator of early risk, aiding the identification of children at the highest risk for later behavioral problems.
Prevalence and clinical features of intraspinal facet cysts after decompression surgery for lumbar spinal stenosis.

OBJECT Although many cases of primary intraspinal facet cysts in the lumbar spine have been reported, there have only been a few reports of postoperative intraspinal facet cysts in the lumbar spine. The purpose of this study was to investigate the prevalence and clinical features of postoperative intraspinal facet cysts in the lumbar spine. METHODS Data from 81 patients undergoing microendoscopic posterior decompression to treat lumbar spinal stenosis were reviewed. The development of a postoperative intraspinal facet cyst was observed using MR imaging during 1 year after surgery. If the patient demonstrated a postoperative intraspinal facet cyst, additional MR imaging was performed to evaluate the natural course of the cyst. Furthermore, the authors conducted a comparative evaluation to identify the factors associated with the causes of cyst development. RESULTS A postoperative intraspinal facet cyst developed in 7 patients (8.6%) during 1 year after surgery. Spondylotic spinal stenosis, degenerative spondylolisthesis, and degenerative scoliosis were revealed before surgery in 2, 4, and 1 patient, respectively. In 5 patients, the cysts developed within 3 months after surgery. Although 3 patients exhibited symptoms caused by cyst development, all symptoms were relieved by conservative treatment. On radiographic evaluations, postoperative segmental spinal instability, including a progression of spondylolisthesis and disc degeneration, was revealed in 6 (86%) of the 7 patients. Spontaneous regression of the cysts was observed in 5 (71%) of these 7 patients. On comparative evaluation of patients with and without postoperative intraspinal facet cysts, the presence of segmental spinal instability before surgery (including degenerative spondylolisthesis) and the appearance of postoperative segmental spinal instability were related to the development of the cysts. CONCLUSIONS The prevalence of postoperative intraspinal facet cysts, including asymptomatic cysts, was 8.6% during 1 year after decompression surgery for lumbar spinal stenosis. The development of postoperative intraspinal facet cysts was related to the presence of segmental spinal instability before surgery (including degenerative spondylolisthesis) and postoperative segmental spinal instability, including a progression of spondylolisthesis and disc degeneration after surgery. A postoperative intraspinal facet cyst, which can be expected to regress spontaneously with a probability > 50%, should be recognized as one of the postoperative complications of decompression surgery for lumbar spinal stenosis.
SOBRINA Spanish study—analysing the frequency, cost and adverse events associated with overuse in primary care: protocol for a retrospective cohort study

Introduction Several institutions and quality national agencies have fostered the creation of recommendations on what not to do to reduce overuse in clinical practice. In primary care, their impact has hardly been studied. The frequency of adverse events (AEs) associated with doing what must not be done has not been analysed, either. The aim of this study is to measure the frequency of overuse and AEs associated with doing what must not be done (commission errors) in primary care and their cost. Methods and analysis A coordinated, multicentric, national project. A retrospective cohort study using computerised databases of primary care medical records from national agencies and regional health services will be conducted to analyse the frequency of the overuse due to ignore the do-not-do recommendations, and immediately afterwards, depending on their frequency, a representative random sample of medical records will be reviewed with algorithms (triggers) that determine the frequency of AEs associated with these recommendations. Cost will determine by summation of the direct costs due to the consultation, pharmacy, laboratory and imaging activities according to the cases. Ethics and dissemination The study protocol has been approved by the Ethics Committee of Primary Care Research of the Valencian Community. We aim to disseminate the findings through international peer-reviewed journals and on the website (http://www.nohacer.es/). Outcomes will be used to incorporate algorithms into the electronic history to assist in making clinical decisions. Trial registration number NCT03482232; Pre-results.
Comparing Longitudinal Behavior Changes in the Primary Progressive Aphasias.

BACKGROUND Differentiating between primary progressive aphasia (PPA) variants based on the profile of language deficits can be difficult in a proportion of patients. Further, little is presently know about the pattern of longitudinal changes in behavior in PPA variants. OBJECTIVE To determine the presence of behavioral changes in the main variants of PPA: semantic (sv-PPA), nonfluent/agrammatic (nfv-PPA), and logopenic (lv-PPA), and establish the course of these changes over time. METHODS We measured behavioral changes in 73 prospectively recruited PPA (30 sv-PPA, 22 nfv-PPA, and 21 lv-PPA), as well as 33 behavioral variant frontotemporal dementia (bv-FTD) and 31 Alzheimer's disease (AD) patients, at baseline and after 1 year, using the Cambridge Behavioural Inventory Revised. All included patients had mild dementia severity at baseline. RESULTS Both at baseline and follow-up, sv-PPA exhibited significantly more behavioral disturbances of the type characteristic of bv-FTD compared with other PPA variants. 74% of sv-PPA patients with mild dementia severity exhibited at least one behavior disturbance at baseline, which increased to 84% during follow-up. Behavioral symptoms did not differ between nfv-PPA and lv-PPA groups at baseline. At follow-up, however, empathy loss was significantly more pronounced in nfv-PPA. The prevalence and course of behavioral symptoms in lv-PPA was similar to that found in AD. CONCLUSIONS sv-PPA show more prominent FTD-like behavioral disturbances compared with other PPA variants which typically emerge already early in the disease course. Empathy loss may be an important factor that helps differentiating nfv-PPA from lv-PPA. Our results may allow improved prediction of likely progression in behavioral symptoms across the PPA variants.
Aberrant Calcium Signals in Reactive Astrocytes: A Key Process in Neurological Disorders

Astrocytes are abundant cells in the brain that regulate multiple aspects of neural tissue homeostasis by providing structural and metabolic support to neurons, maintaining synaptic environments and regulating blood flow. Recent evidence indicates that astrocytes also actively participate in brain functions and play a key role in brain disease by responding to neuronal activities and brain insults. Astrocytes become reactive in response to injury and inflammation, which is typically described as hypertrophy with increased expression of glial fibrillary acidic protein (GFAP). Reactive astrocytes are frequently found in many neurological disorders and are a hallmark of brain disease. Furthermore, reactive astrocytes may drive the initiation and progression of disease processes. Recent improvements in the methods to visualize the activity of reactive astrocytes in situ and in vivo have helped elucidate their functions. Ca2+ signals in reactive astrocytes are closely related to multiple aspects of disease and can be a good indicator of disease severity/state. In this review, we summarize recent findings concerning reactive astrocyte Ca2+ signals. We discuss the molecular mechanisms underlying aberrant Ca2+ signals in reactive astrocytes and the functional significance of aberrant Ca2+ signals in neurological disorders.
Vulvar basal cell carcinoma: clinical features and treatment outcomes from a tertiary-care centre.

We retrospectively reviewed the clinical features, management and outcomes of patients diagnosed with basal cell carcinoma (BCC) of the vulva at the Gynaecological Cancer Centre, KK Women's and Children's Hospital, Singapore, between 1 January 2000 and 28 February 2014. Patients with vulvar BCC were identified from the cancer registry, and their medical records reviewed and analysed. A total of 11 patients with vulvar BCC were identified. Mean age at diagnosis was 63 (range 30¬-85) years. Ethnically, ten patients were Chinese and one was Malay. Average time from onset of symptoms to diagnosis was 13.8 (range 2-60) months. The most common presenting symptoms were lump and pruritus. All patients were managed surgically. Recurrence was noted in only one patient. Vulvar BCC, although rare, has an excellent prognosis, when managed appropriately. Histological diagnosis of all persistent papules, plaques and pigmented lesions is important for early diagnosis.
Older age and HDL-cholesterol as independent predictors of liver fibrosis assessed by BARD score.

BACKGROUND It is known that non-alcoholic fatty liver disease (NAFLD), and in particular non-alcoholic steatohepatitis, can progress to advanced fibrosis. However, pathophysiological mechanisms implicated in this evolution are not elucidated yet. We aimed to investigate the independent predictors of liver fibrosis in patients with NAFLD, determined by BARD score, one of the most used algorithms for fibrosis evaluation. METHODS This prospective study enrolled a total of 301 participants with NAFLD, as determined by a Fatty Liver Index (FLI) ≥60. All patients were categorized into two groups: with no/mild fibrosis (BARD score 1, N.=62) and with advanced fibrosis (BARD score 2, 3 and 4 N.=239). RESULTS Serum high density lipoprotein cholesterol (HDL-c), glucose and glycated hemoglobin were higher (P=0.028, P<0.001 and P=0.002, respectively), whereas serum transaminases and gamma glutamil transferase levels were lower in patients with advanced fibrosis than in those with no/mild fibrosis (P=0.010, P<0.001 and P=0.005, respectively). There were no significant differences in oxidative stress (i.e., advanced oxidant protein products and malondialdehyde) and anti-oxidative protection markers (i.e., catalase) between patients with no/mild fibrosis and advanced fibrosis. Multivariate ordinal regression analysis showed independent associations and predictions of ages (OR=1.071, 95% CI 1.004-1.097, P<0.001), and HDL-c levels (OR=2.549, 95% CI 1.087-5.989, P=0.032) on BARD score categories in patients with NAFLD. CONCLUSIONS In conclusion, we found that older age and higher HDL-c, are independent predictors for advanced liver fibrosis assessed with the BARD score. Future investigations are needed to further explore this relationship.
Swarm Chemistry

We propose swarm chemistry, a new artificial chemistry framework that uses artificial swarm populations as chemical reactants. Reaction in swarm chemistry is not determined by predefined reaction rules as commonly assumed in typical artificial chemistry studies, but is spontaneously achieved by the emergence of a new spatiotemporal pattern of collective behavior through the kinetic interaction between multiple chemical species. We developed a prototype of an interactive simulation tool with which one can explore the dynamics of swarm chemistry using an interactive evolutionary method. Several preliminary results are reported to illustrate the characteristics and effectiveness of this framework, including spontaneous segregation of distinct chemical species, production and restriction of movements, and interactive design of complex biological-looking structures.
Potential Use of the Maillard Reaction for Pharmaceutical Applications: Gastric and Intestinal Controlled Release Alginate-Albumin Beads

In this study, bovine serum albumin (BSA) and alginate (ALG) conjugates were synthesized by the Maillard reaction in order to evaluate their potential to develop controlled release drug delivery systems. The progress of the Maillard reaction was evidenced using ultraviolet (UV) absorbance, determination of BSA remaining free amino groups, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). BSA-ALG conjugates possessed enhanced and tunable viscosity, foamability and foam stability. Foam generated from BSA-ALG conjugate solution was used to prepare floating gastroretentive calcium ALG beads. Unlike traditional ALG beads, BSA-ALG foam beads were able to float and sustain the ciprofloxacin (CIP) release in gastric medium. Interestingly, intestinal beads made of ALG, BSA-ALG physical mixture and BSA-ALG conjugate resulted in different release rates and orders of indomethacin (IND) in simulated intestinal fluids; while beads based on a physical mixture of BSA-ALG resulted in a first order sustained release profile, both systems based on ALG and BSA-ALG conjugate displayed zero order sustained release profiles with IND being released at a slower rate from the conjugate beads.
Pulmonary toxicity following inhalation exposure to VX in anesthetized rats: Possible roles for compromised immunity and oxidative stress-induced lung injury

Abstract The nerve agent VX is one of the most deadly threat agents available in weapons stockpiles for intentional release. While mostly considered a percutaneous toxicant, it can be fatal when aerosolized. The objective of this study was to investigate toxic responses in the lung up to two weeks following a single 10-minute exposure to inhaled VX. Anesthetized rats were exposed singly and only once to VX. The nebulization rate in this system was 0.2–0.3 ml per minute with the delivery of a consistent particle size of 2.1 µm. Following exposure, all rats were removed from the ventilator and allowed to recover in the glovebox for 10–15 minutes. Results showed that inhaled VX altered several respiratory parameters and caused increased lung resistance up to 6 h post-exposure (PE). There was a trending increase in SOD and xanthine oxidoreductase (XOR) activities, both of which are indicative of oxidative stress. Based on increased lung tissue p38 signaling, MAP kinase expression was activated after VX exposure. IL-6 expression was also increased at 6 h post-inhalation for the 31.6 mg/m3 exposed group. Innate survival response mechanisms in rats may be present due to increased lung tissue mRNA AChE expression 6 h after exposure. Immunohistochemistry showed reduced staining for surfactant D and increased expression of iNOS, indicating that the activation of •NO precursor pathways. Bronchoalveloar lavage fluid (BALF) results from 1 h to 2 weeks PE show that inflammatory cells are highly active as evidenced by the increased production of cytokines and chemokines. This is the first study linking VX-induced lung injury to a possible innate survival amplification of AChE and possibly compromised immune function. These results could supplement medical treatment strategies with regard to therapeutic approaches against VX inhalational challenge.
Inhibition of endothelial Progenitor Cells Inhibition in the first 24 hours of an Acute Ischemic Cerebrovascular Event.

BACKGROUND Endothelial progenitor cells may have a role in ongoing endothelial repair. Impaired mobilization or depletion of these cells may contribute to progression of vascular disease. Our hypothesis was that endothelial progenitor cells would be suppressed in patients with acute cerebrovascular event based on our previous study that found severe endothelial dysfunction in those patients. OBJECTIVES To study the ability of patients with acute stroke to build colonies of endothelial progenitor cells. METHODS We studied the number of colony-forming units of endothelial progenitor cells (CFU-EPCs) from the peripheral blood of 22 male patients with a first-time acute stroke (age 58.09 ± 9.8 years) and 13 healthy men (34 ± 6.7 years), 8 female patients with a first-time acute stroke (54.6 ± 10.3 years) and 6 healthy women (38.3 ± 11.6 years). Endothelium-dependent function was assessed by high-resolution ultrasonography of the brachial artery that measured the change in diameter of the artery by flow-mediated diameter percent change (FMD%). All patients had strokes demonstrated by a brain computed tomography (CT) scan done on admission. Peripheral blood was drawn soon after admission and was processed for endothelial progenitor cells in culture. RESULTS Thirty patients without known cardiovascular risk factors and who did not take any medications were admitted with a first-time acute stroke. All demonstrated a strong correlation between CFU-EPCs grown in culture and endothelial dysfunction (r = 0.827, P < 0.01). Endothelial dysfunction with an FMD% of -2.2 ± 9.7% was noted in male patients vs. 17.5 ± 6.8% in healthy males (P = 0.0001), and -7.2 ± 10.1% in female patients vs. 25.1 ± 7.1% in healthy females (P = 0.0001). CFU-EPCs were 5.5 ± 6.3 in men with stroke vs. 23.75 ± 5.3 in healthy males (P = 0.0001), and 7.6 ± 4.9 in women with stroke vs. 22.25 ± 6.7 in healthy females (P = 0.0004).