Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment of the Acute Alcohol Withdrawal State: A Comparison of Four Drugs

T seriousness of alcohol withdrawal and its widespread occur­ rence in the 166 Veterans Administration hospitals in the 1960’s was the principal reason this pivotal study was conducted. The important work by Kaim and colleagues has endured over the years, because alcohol withdrawal still is common, potentially life threatening, and often not recognized and treated promptly and effectively. Kaim and colleagues studied the ef­ ficacy of four drugs—chlordiazepoxide (a benzodiazepine), chlorpromazine ( a n e u r o l e p t i c o r a n t i p s y c h o t i c agent), hydroxyzine (a sedating anti­ histamine), and thiamine (a vitamin)— commonly used at that time to treat alcohol withdrawal symptoms, specifi­ cally the more serious symptoms of delirium tremens and convulsions. These researchers’ results help estab­ lish the benzodiazepines as drugs of choice in treating alcohol withdrawal. To fully understand the context in which Kaim and colleagues conducted their study, it is useful to consider the state of pharmacological treatment of withdrawal at that time. D u r i n g t h e 1 9 5 0 ’ s a n d e a r l y to mid­1960’s, several initial studies suggested that promazine and chlorpro­ mazine (both antipsychotic medica­ tions) were effective in treating alcohol withdrawal. Later studies did not con­ firm these findings. Moreover, several subsequent studies suggested that the incidence of serious withdrawal symp­ toms, such as seizures and delirium, might actually be higher after adminis­ tration of these two agents (Sereny and Kalant 1965). Pharmacologically, based on today’s knowledge, compli­ cations such as confusion and delirium would be expected. These tranquilizing agents decrease the seizure threshold by making the brain more susceptible to spontaneous cellular electrical activ­ ity. The agents also have properties (i.e., anticholinergic) that disrupt cellu­ l ar commu nic atio n, re su l t i ng i n changes in body function (e.g. gas­ trointestinal disorders). C hlo rd i az ep o xid e w as a no th er medication studied by Kaim and col­ leag ues in thei r article. Chlordia­ zepoxide was marketed in 1961. It is interesting to note that in that same year, Kaim and Rostenstein (1961) opined that based on clinical evidence,
Raman Tweezers as a Diagnostic Tool of Hemoglobin-Related Blood Disorders

This review presents the development of a Raman Tweezers system for detecting hemoglobin-related blood disorders at a single cell level. The study demonstrates that the molecular fingerprint insight provided by Raman analysis holds great promise for distinguishing between healthy and diseased cells in the field of biomedicine. Herein a Raman Tweezers system has been applied to investigate the effects of thalassemia, a blood disease quite diffuse in the Mediterranean Sea region. By resonant excitation of hemoglobin Raman bands, we examined the oxygenation capability of normal, alpha- and beta-thalassemic erythrocytes. A reduction of this fundamental red blood cell function, particularly severe for beta-thalassemia, has been found. Raman spectroscopy was also used to draw hemoglobin distribution inside single erythrocytes; the results confirmed the characteristic anomaly (target shape), occurring in thalassemia and some other blood disorders. The success of resonance Raman spectroscopy for thalassemia detection reported in this review provide an interesting starting point to explore the application of a Raman Tweezers system in the analysis of several blood disorders.
MicroRNA Expression Differences in Human Hematopoietic Cell Lineages Enable Regulated Transgene Expression

Blood microRNA (miRNA) levels have been associated with and shown to participate in disease pathophysiology. However, the hematopoietic cell of origin of blood miRNAs and the individual blood cell miRNA profiles are poorly understood. We report the miRNA content of highly purified normal hematopoietic cells from the same individuals. Although T-cells, B-cells and granulocytes had the highest miRNA content per cell, erythrocytes contributed more cellular miRNA to the blood, followed by granulocytes and platelets. miRNA profiling revealed different patterns and different expression levels of miRNA specific for each lineage. miR-30c-5p was determined to be an appropriate reference normalizer for cross-cell qRT-PCR comparisons. miRNA profiling of 5 hematopoietic cell lines revealed differential expression of miR-125a-5p. We demonstrated endogenous levels of miR-125a-5p regulate reporter gene expression in Meg-01 and Jurkat cells by (1) constructs containing binding sites for miR-125a-5p or (2) over-expressing or inhibiting miR-125a-5p. This quantitative analysis of the miRNA profiles of peripheral blood cells identifies the circulating hematopoietic cellular miRNAs, supports the use of miRNA profiles for distinguishing different hematopoietic lineages and suggests that endogenously expressed miRNAs can be exploited to regulate transgene expression in a cell-specific manner.
Panel: the Need of Formats for Streaming and Storing Music-Related movement and Gesture Data

The last decade has seen the development of standards for music notation (MusicXML), audio analysis (SDIF), and sound control (OSC), but there are no widespread standards, nor structured approaches, for handling music-related movement, action and gesture data. This panel will address the needs for such formats and standards in the computer music community, and discuss possible directions for future development.
Subtilase Cytotoxin-Coding Genes in Verotoxin-Producing Escherichia coli Strains from Sheep and Goats Differ from Those from Cattle

ABSTRACT Subtilase cytotoxin (SubAB) from verotoxin (VT)-producing Escherichia coli (VTEC) strains was first described in the 98NK2 strain and has been associated with human disease. However, SubAB has recently been found in two VT-negative E. coli strains (ED 591 and ED 32). SubAB is encoded by two closely linked, cotranscribed genes (subA and subB). In this study, we investigated the presence of subAB genes in 52 VTEC strains isolated from cattle and 209 strains from small ruminants, using PCR. Most (91.9%) VTEC strains from sheep and goats and 25% of the strains from healthy cattle possessed subAB genes. The presence of subAB in a high percentage of the VTEC strains from small ruminants might increase the pathogenicity of these strains for human beings. Some differences in the results of PCRs and in the association with some virulence genes suggested the existence of different variants of subAB. We therefore sequenced the subA gene in 12 strains and showed that the subA gene in most of the subAB-positive VTEC strains from cattle was almost identical (about 99%) to that in the 98NK2 strain, while the subA gene in most of the subAB-positive VTEC strains from small ruminants was almost identical to that in the ED 591 strain. We propose the terms subAB1 to describe the SubAB-coding genes resembling that in the 98NK2 strain and subAB2 to describe those resembling that in the ED 591 strain.
Advances in clinical research in sickle cell disease

Sickle cell disease continues to cause significant morbidity and mortality despite increases in life expectancy. This review looks at recent translational research in sickle cell disease, covering the red cell membrane, the vascular endothelium, local and systemic inflammation and the potentially pivotal role of nitric oxide as a key regulator of sickle cell complications. Clinical research reviewed includes pulmonary hypertension, which is emerging as a particularly deadly scourge of adults with any haemolytic anaemia, and newer insights into older, more established complications and treatments, such as red cell transfusions, the need for and use of iron chelation and avascular necrosis. Finally, recent studies about those factors that affect the day‐to‐day lives of persons with sickle cell disease, pain and neuropsychiatric functioning, are discussed.
Nephroprotective effect of Bauhinia variegata (Linn.) whole stem extract against cisplatin-induced nephropathy in rats

The nephroprotective activity of the ethanolic extract of Bauhinia variegata (Linn.) whole stem against cisplatin-induced nephropathy was investigated by an in vivo method in rats. Acute nephrotoxicity was induced by i.p. injection of cisplatin (7 mg/kg of body weight (b.w.)). Administration of ethanol extract at dose levels of 400 and 200 mg/kg (b.w.) to cisplatin-intoxicated rats for 14 days attenuated the biochemical and histological signs of nephrotoxicity of cisplatin in a dose-dependent fashion. Ethanol extract at 400 mg/kg decreased the serum level of creatinine (0.65 ± 0.09; P<0.001) and urea (32.86 ± 5.88; P<0.001) associated with a significant increase in body weight (7.16 ± 1.10; P<0.001) and urine volume output (11.95 ± 0.79; P<0.05) as compared to the toxic control group. The ethanol extract of B. variegata at 400 mg/kg (b.w.) exhibited significant and comparable nephroprotective potential to that of the standard polyherbal drug cystone. The statistically (one-way-ANOVA followed by Tukey-Kramer multiple comparison) processed results suggested the protective action of B. variegate whole stem against cisplatin-induced nephropathy.
The insulator protein Suppressor of Hairy-wing is an essential transcriptional repressor in the Drosophila ovary

Suppressor of Hairy-wing [Su(Hw)] is a DNA-binding factor required for gypsy insulator function and female germline development in Drosophila. The insulator function of the gypsy retrotransposon depends on Su(Hw) binding to clustered Su(Hw) binding sites (SBSs) and recruitment of the insulator proteins Centrosomal Protein 190 kD (CP190) and Modifier of mdg4 67.2 kD (Mod67.2). By contrast, the Su(Hw) germline function involves binding to non-clustered SBSs and does not require CP190 or Mod67.2. Here, we identify Su(Hw) target genes, using genome-wide analyses in the ovary to uncover genes with an ovary-bound SBS that are misregulated upon Su(Hw) loss. Most Su(Hw) target genes demonstrate enriched expression in the wild-type CNS. Loss of Su(Hw) leads to increased expression of these CNS-enriched target genes in the ovary and other tissues, suggesting that Su(Hw) is a repressor of neural genes in non-neural tissues. Among the Su(Hw) target genes is RNA-binding protein 9 (Rbp9), a member of the ELAV/Hu gene family. Su(Hw) regulation of Rbp9 appears to be insulator independent, as Rbp9 expression is unchanged in a genetic background that compromises the functions of the CP190 and Mod67.2 insulator proteins, even though both localize to Rbp9 SBSs. Rbp9 misregulation is central to su(Hw)-/- sterility, as Rbp9+/-, su(Hw)-/- females are fertile. Eggs produced by Rbp9+/-, su(Hw)-/- females show patterning defects, revealing a somatic requirement for Su(Hw) in the ovary. Our studies demonstrate that Su(Hw) is a versatile transcriptional regulatory protein with an essential developmental function involving transcriptional repression.
Diclofenac Distinguishes among Homomeric and Heteromeric Potassium Channels Composed of KCNQ4 and KCNQ5 Subunits

KCNQ4 and KCNQ5 potassium channel subunits are expressed in vascular smooth muscle cells, although it remains uncertain how these subunits assemble to form functional channels. Using patch-clamp techniques, we compared the electrophysiological characteristics and effects of diclofenac, a known KCNQ channel activator, on human KCNQ4 and KCNQ5 channels expressed individually or together in A7r5 rat aortic smooth muscle cells. The conductance curves of the overexpressed channels were fitted by a single Boltzmann function in each case (V0.5 values: −31, −44, and −38 mV for KCNQ4, KCNQ5, and KCNQ4/5, respectively). Diclofenac (100 μM) inhibited KCNQ5 channels, reducing maximum conductance by 53%, but increased maximum conductance of KCNQ4 channels by 38%. The opposite effects of diclofenac on KCNQ4 and KCNQ5 could not be attributed to the presence of a basic residue (lysine) in the voltage-sensing domain of KCNQ5, because mutation of this residue to neutral glycine (the residue present in KCNQ4) resulted in a more effective block of the channel. Differences in deactivation rates and distinct voltage-dependent effects of diclofenac on channel activation and deactivation observed with each of the subunit combinations (KCNQ4, KCNQ5, and KCNQ4/5) were used as diagnostic tools to evaluate native KCNQ currents in vascular smooth muscle cells. A7r5 cells express only KCNQ5 channels endogenously, and their responses to diclofenac closely resembled those of the overexpressed KCNQ5 currents. In contrast, mesenteric artery myocytes, which express both KCNQ4 and KCNQ5 channels, displayed whole-cell KCNQ currents with properties and diclofenac responses characteristic of overexpressed heteromeric KCNQ4/5 channels.
High prevalence of detectable deep venous thrombosis in patients with acute pulmonary embolism.

STUDY OBJECTIVES Because specific studies are unavailable, the exact prevalence of detectable "residual" deep venous thrombosis (DVT) in patients with acute pulmonary embolism (PE) is unknown. DESIGN Review of clinical records and radiologic documents of consecutive patients. SETTING Pulmonary diseases and radiology departments at a university hospital. PATIENTS All patients hospitalized in the Department of Pulmonary Diseases with a diagnosis of acute PE during a 5-year period (1984 to 1988). During this period, the diagnosis of PE was based exclusively on pulmonary angiography, and bilateral lower limb venography was routine in patients with proven acute PE. MEASUREMENTS AND RESULTS Among 228 consecutive patients with angiography-proven PE, 213 underwent bilateral lower limb venography within 48 h of the diagnosis. Venography demonstrated DVT in 174 patients (81.7%; 95% confidence interval, 76.5 to 86.9%), including 128 patients (60%) with proximal DVT. Signs or symptoms of DVT were present in only 72 patients (42%) with DVT. The prevalence of detectable DVT was significantly lower in patients with recent pelvic surgery or delivery (6 of 12, 50%) than in the other patients, whatever their individual risk factors (p < 0.05). The mean pulmonary vascular obstruction was significantly lower in patients with normal venography than in patients with detectable DVT (37.6 +/- 20.9% vs 48.4 +/- 21.7%; p = 0.007). CONCLUSIONS Lower limb venography demonstrates a high prevalence (82%) of residual DVT in patients with angiography-proven PE. These data should be taken into account in the diagnostic and therapeutic management of patients with suspected or proven PE.
Green Conversion of Agroindustrial Wastes into Chitin and Chitosan by Rhizopus arrhizus and Cunninghamella elegans Strains

This article sets out a method for producing chitin and chitosan by Cunninghamella elegans and Rhizopus arrhizus strains using a green metabolic conversion of agroindustrial wastes (corn steep liquor and molasses). The physicochemical characteristics of the biopolymers and antimicrobial activity are described. Chitin and chitosan were extracted by alkali-acid treatment, and characterized by infrared spectroscopy, viscosity and X-ray diffraction. The effectiveness of chitosan from C. elegans and R. arrhizus in inhibiting the growth of Listeria monocytogenes, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella enterica, Escherichia coli and Yersinia enterocolitica were evaluated by determining the minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC). The highest production of biomass (24.60 g/L), chitin (83.20 mg/g) and chitosan (49.31 mg/g) was obtained by R. arrhizus. Chitin and chitosan from both fungi showed a similar degree of deacetylation, respectively of 25% and 82%, crystallinity indices of 33.80% and 32.80% for chitin, and 20.30% and 17.80% for chitosan. Both chitin and chitosan presented similar viscosimetry of 3.79–3.40 cP and low molecular weight of 5.08 × 103 and 4.68 × 103 g/mol. They both showed identical MIC and MBC for all bacteria assayed. These results suggest that: agricultural wastes can be produced in an environmentally friendly way; chitin and chitosan can be produced economically; and that chitosan has antimicrobial potential against pathogenic bacteria.
Predictors of Mortality and Limb Loss in Necrotizing Soft Tissue Infections

Necrotizing soft tissue infections (NSTIs) require prompt diagnosis and treatment. Early identification of patients at greatest risk of limb amputation and death may help in targeting aggressive medical and surgical management. The aim of this study was to assess predictors of limb loss and mortality in patients with NSTI based on admission variables. We performed a retrospective review of two hospitals that care for a large volume of patients with NSTI. Univariate and multi-variable analyses were used to determine the association of admission biochemical markers to limb loss and mortality. Of 174 patients with NSTI, there were 19 deaths (10.9%) and 42 required amputations (24.1%). Multivariable logistic regression analysis revealed that only arterial lactate was predictive for both mortality (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1 to 2.0; P = 0.009) and limb loss (OR, 1.3; 95% CI, 1.0 to 1.7; P = 0.02). In patients with a suspected NSTI, an arterial lactate should be ordered early on to guide aggressive therapeutic interventions and to provide information with regard to long-term outcomes of amputation and death that is needed for early discussion with the patient and family.
Peptide-Specific Antibody Measurement in the Sera of Immunized Mice , C 5 a Level in Plasma , and C 5 aR Levels in Lymph Nodes After immunization of

The anaphylatoxin C5a, generated by activation of the innate immunity complement component C5, is a potent protein fragment. Binding of C5a to the guanine nucleotidebinding protein (G-protein)-coupled C5a receptor (C5aR) present in immune-inflammatory cells, including monocytes, macrophages, neutrophils, and T cells, leads to proinflammatory activation. C5a exerts its effect by activating the C5aR. The C5aR, also known as complement component 5aR-1 (C5AR1) or cluster of differentiation 88 (CD88), belongs to the rhodopsinlike receptor superfamily, characterized by 7 hydrophobic, transmembrane helical regions connected by 3 extracellular and 3 intracellular loops. Among the innate immune components, C5, C5a, and C5aR are abundant and suggested to play critical roles in atherogenesis. Atherosclerosis is increasingly recognized as a complex chronic inflammatory disease of the arterial walls, as evidenced by the presence of inflammatory cells, activated immune cells, and cytokines in lesions, all of which indicate involvement of the immune system. Monocyte-to-macrophage differentiation and low– density lipoprotein (LDL) oxidation play a pivotal role in early atherogenesis. Macrophages are key players in many aspects of human physiology and disease, including atherosclerosis. By taking up modified LDL (oxidized or acetylated), monocytederived macrophages are turned into fat-loaded macrophages residing in the vessel wall, furthering the local inflammatory response and leading to progression of the atherosclerotic plaque. Both innate and adaptive immunities play roles in various stages of atherosclerosis. The binding of C5a to the C5aR is postulated to occur via a 2-site binding mechanism. The basic core of C5a is thought to interact with acidic residues in the receptor amino (N)-terminus, whereas the carboxyl (C)-terminal domain of C5a binds in a pocket formed by largely hydrophobic residues within the transmembrane helices (cylinders 1–7) of the C5aR. In addition, residues between 1 and 35 in the N-terminal domain of C5aR are essential for the interaction with the chemotaxis inhibitory protein of
Converging evidence for the relevance of alternative sets: data from NPs with focus sensitive particles in German

abstract Recent psycholinguistic studies on the reality of alternative sets in processing focus NPs have shown that focus particles like ‘only’ play a special role in activating the mental representation of alternatives to focused nouns. In this paper we present a new corpus study which provides converging evidence to support psycholinguistic findings and suggests that alternatives preceded by a focus particle are not only more activated in experimental contexts, but are also more likely to be discussed in the subsequent context. To this end we develop and evaluate inter-annotator agreement on two novel annotation tasks in naturally occurring German corpus data: recognition of nominal alternatives in general without any context, and recognition of alternatives in the context of sentence pairs. We show that while annotators agree poorly on the first, they agree strongly on the second. We also develop a concept of ‘alternative density’, the number of alternatives realized in a sentence following a target NP, and present a mixed-effects model showing a very significant rise in density after the presence of German nur ‘only’ independently of other factors.
Separation of harmonic sounds using multipitch analysis and iterative parameter estimation

A signal processing method for the separation of concurrent harmonic sounds is described. The method is based on a two-stage approach. First, a multipitch estimator is applied to find initial sound parameters which are reliable, but inaccurate and static. In a second stage, more accurate and time-varying sinusoidal parameters are estimated in an iterative procedure, which imposes certain constraints for the amplitudes and frequencies between the components of each sound. The proposed algorithm makes it possible to reconstruct separated sounds that are perceptually close to the original ones before mixing. Experimental data comprised sung vowels and 26 musical instruments. Sound separation was performed for random sound mixtures ranging from one to six simultaneous sounds. The system is able to produce meaningful results in all polyphonies, the quality of separated sounds gradually degrading along with the polyphony.
Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association

Cardiovascular disease (CVD) is the leading global cause of death, accounting for 17.3 million deaths per year. Preventive treatment that reduces CVD by even a small percentage can substantially reduce, nationally and globally, the number of people who develop CVD and the costs of caring for them. This American Heart Association presidential advisory on dietary fats and CVD reviews and discusses the scientific evidence, including the most recent studies, on the effects of dietary saturated fat intake and its replacement by other types of fats and carbohydrates on CVD. In summary, randomized controlled trials that lowered intake of dietary saturated fat and replaced it with polyunsaturated vegetable oil reduced CVD by ≈30%, similar to the reduction achieved by statin treatment. Prospective observational studies in many populations showed that lower intake of saturated fat coupled with higher intake of polyunsaturated and monounsaturated fat is associated with lower rates of CVD and of other major causes of death and all-cause mortality. In contrast, replacement of saturated fat with mostly refined carbohydrates and sugars is not associated with lower rates of CVD and did not reduce CVD in clinical trials. Replacement of saturated with unsaturated fats lowers low-density lipoprotein cholesterol, a cause of atherosclerosis, linking biological evidence with incidence of CVD in populations and in clinical trials. Taking into consideration the totality of the scientific evidence, satisfying rigorous criteria for causality, we conclude strongly that lowering intake of saturated fat and replacing it with unsaturated fats, especially polyunsaturated fats, will lower the incidence of CVD. This recommended shift from saturated to unsaturated fats should occur simultaneously in an overall healthful dietary pattern such as DASH (Dietary Approaches to Stop Hypertension) or the Mediterranean diet as emphasized by the 2013 American Heart Association/American College of Cardiology lifestyle guidelines and the 2015 to 2020 Dietary Guidelines for Americans.