Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic staging and risk factor scoring for gestational trophoblastic disease

It is proposed that a dynamic staging and risk factor scoring system is introduced for the classification of gestational trophoblastic disease as a logical development of the system presently used by the FIGO. Modern computer technology permits such change as the disease changes and particularly if it progresses. By allowing a change of both stage and risk factor score for each patient reported, a dynamic scoring system results. Moreover, such a system allows the introduction of more clinical detail than is permitted by the present FIGO system. FIGO combining its anatomic staging, first devised by Professor Song of Beijing, with the World Health Organization risk factor scoring, first devised by Professor Kenneth Bagshawe of Charing Cross Hospital, London, in 2002 was a significant progress. The most important change of the FIGO 2002 modification was that criteria were defined for the diagnosis of postmolar gestational trophoblastic neoplasia. However, hydatidiform mole still has no place in that classification. Also, the time when the staging occurs is not mandated. The present FIGO classification allows for no change in the status of the patient. A dynamic staging and risk factor scoring system would allow such changes to be recorded and, therefore, permit a more precise account of the patient's disease. A third issue is whether invasive mole should be included in the classification, as the Japanese Gynecologic Cancer Society insists is necessary. This problem may also be solved by the use of a dynamic risk factor scoring system.
Heterocyst-specific flavodiiron protein Flv3B enables oxic diazotrophic growth of the filamentous cyanobacterium Anabaena sp. PCC 7120

Significance Cyanobacterial flavodiiron proteins (FDPs) comprise a protein family with unique modular structure and photoprotective functions in an oxygenic environment. It is conceivable that FDPs have made the development of oxygenic photosynthesis possible in cyanobacteria. Here, we report the ability of specific FDPs to reduce O2 directly to water in heterocyst-forming filamentous cyanobacteria, not only to support the photosynthetic machinery, but also to prevent oxidative damage of the N2-fixing enzyme nitrogenase. Whilst in the ancient environment, N2 fixation was secured from O2 inhibition, the later increase of atmospheric O2 may have initiated an important role for FDP-mediated protection of nitrogenase in maintaining the N2-fixing activity of cyanobacteria. Flavodiiron proteins are known to have crucial and specific roles in photoprotection of photosystems I and II in cyanobacteria. The filamentous, heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120 contains, besides the four flavodiiron proteins Flv1A, Flv2, Flv3A, and Flv4 present in vegetative cells, two heterocyst-specific flavodiiron proteins, Flv1B and Flv3B. Here, we demonstrate that Flv3B is responsible for light-induced O2 uptake in heterocysts, and that the absence of the Flv3B protein severely compromises the growth of filaments in oxic, but not in microoxic, conditions. It is further demonstrated that Flv3B-mediated photosynthetic O2 uptake has a distinct role in heterocysts which cannot be substituted by respiratory O2 uptake in the protection of nitrogenase from oxidative damage and, thus, in an efficient provision of nitrogen to filaments. In line with this conclusion, the Δflv3B strain has reduced amounts of nitrogenase NifHDK subunits and shows multiple symptoms of nitrogen deficiency in the filaments. The apparent imbalance of cytosolic redox state in Δflv3B heterocysts also has a pronounced influence on the amounts of different transcripts and proteins. Therefore, an O2-related mechanism for control of gene expression is suggested to take place in heterocysts.
Phase balancing in globally connected networks of Liénard oscillators

We synthesize a feedback for a fully connected network of identical Liénard-type oscillators such that the phase-balanced equilibrium — the mode where the centroid of the coupled oscillators in polar coordinates is at the origin — is asymptotically stable, and the phase-synchronized equilibrium is unstable. Our approach hinges on a coordinate transformation of the oscillator dynamics to polar coordinates, and periodic averaging theory to simplify the examination of multiple time-scale behavior. Using Lyapunov- and linearization-based arguments, we demonstrate that the oscillator dynamics have the same radii and balanced phases in steady state for a large set of initial conditions. Numerical simulation results are presented to validate the analyses.
Solid‐state NMR studies of the molecular structure of Taxol

Solid‐state 13C{1H} cross‐polarization/magic angle spinning spectroscopy (CP/MAS) has been utilized to extract the molecular structure information of Taxol, which is an anti‐tumor therapeutic medicine extracted from the yew bark. The 13C signals have chemical shift values quite consistent with those measured in solution phase, and the overall chemical shift range is over 200 ppm. Notably, most of the 13C resonances of the taxane ring have two clearly resolved spectral components except the resonance peaks of C‐15, C‐16 and C‐17, which are located at the central part of the taxane ring. On the basis of our NMR data, we propose that these doublets originate from two slightly different molecular conformations of the taxane ring and still the central part of the ring remains structurally similar. Furthermore, it is demonstrated that the 13C chemical shift difference deduced from the doublet splittings can serve as a direct measure of the structural difference between the two conformations, which could possibly correlate with the anti‐tumor activity of Taxol. Copyright © 2006 John Wiley & Sons, Ltd.
A Comparative Study of the Effect of Clonidine and Tramadol for Control of Shivering Under Spinal Anesthesia

Spinal anesthesia is known to significantly impair thermoregulation through inhibiting vasomotor and shivering responses and through redistributing heat from core body to peripheral tissues with subsequent rapid hypothermia during anesthesia. Among pharmacological therapies a recent meta-analysis, reported use of Clonidine, Tramadol, pethidine, nefopam and ketamine as the most common agents. There are few studies from this region comparing Cloniidne and Tramadol, hence the present study. This was a open label randomized study conducted in a tertiary care hospital in South India, from June 2014 to November 2014. The participants were allocated to receive Clonidine (Group C; n = 40) or Tramadol (Group T; n=40). Group C (n=40) received Clonidine 0.5 μg/kg (intravenously) IV, and group T (n=40) received Tramadol 0.5 mg/kg IV. Patients who developed grade 3 or 4 shivering for at least 3 minutes after spinal anesthesia were included in the study. Student's T test has been used to find the significance of study parameters between two groups of patients, Chisquare/ 2x3 Fisher Exact test has been used to find the significance of study parameters on categorical scale between two or more groups. In the present study, it was observed that both Clonidine and Tramadol are effective in treating post spinal shivering, but the time interval from the commencement of treatment to cessation of shivering is quite less with Clonidine (P<0.01). The response rate was 100% in Clonidine group and recurrence was nil. Complications like hypotension, bradycardia, and dry mouth were observed in Clonidine group and nausea and vomiting in Tramadol group. The sedation score was higher in Clonidine group. Both Clonidine and Tramadol are effective in treating patients with post-spinal anesthesia shivering. The higher incidence of side effects of tramadol, like nausea, vomiting and dizziness, may limit its use as an anti-shivering drug.
The ACTH response to dexamethasone in PTSD.

OBJECTIVE Enhanced negative feedback and reduced adrenal output are two different models that have been put forth to explain the paradoxical observations of increased release of corticotropin-releasing factor in the face of low cortisol levels in posttraumatic stress disorder (PTSD). To discriminate between these models, the authors measured levels of adrenocorticopic hormone (ACTH) and cortisol at baseline and in response to dexamethasone in medically healthy subjects with and without PTSD. Under conditions of enhanced negative feedback inhibition, ACTH levels would not be altered relative to cortisol levels, but the ACTH response to dexamethasone would be augmented, in concert with the enhanced cortisol response to dexamethasone. In contrast, under conditions of reduced adrenal output, ACTH levels would be expected to be higher at baseline relative to cortisol levels, but the ACTH response to dexamethasone would be unchanged in PTSD relative to healthy comparison subjects. METHOD The ACTH and cortisol responses to 0.50 mg of dexamethasone were assessed in 19 subjects (15 men and four women) with PTSD and 19 subjects (14 men and five women) without psychiatric disorder. RESULTS The ACTH-to-cortisol ratio did not differ between groups before or after dexamethasone, but the subjects with PTSD showed greater suppression of ACTH (as well as cortisol) in response to dexamethasone. CONCLUSIONS The data support the hypothesis of enhanced cortisol negative feedback inhibition of ACTH secretion at the level of the pituitary in PTSD. Pituitary glucocorticoid receptor binding, rather than low adrenal output, is implicated as a likely mechanism for this effect.
Cytomegalovirus PP65 antigenemia monitoring as a guide for preemptive therapy: a cost effective strategy for prevention of cytomegalovirus disease in adult liver transplant recipients.

BACKGROUND The aim of the study was to assess the incidence of cytomegalovirus (CMV) infection and disease in adult liver transplant recipients, using routine preemptive therapy guided by the pp65 antigenemia test. METHODS Antigenemia was monitored weekly after liver transplantation (OLTX) for the first 3 months, and once a month for another 3 months. CMV seronegative recipients were treated preemptively for the first positive antigenemia. Seropositive recipients were treated only when their antigenemia count reached a threshold of > or =100 positive cells per 200,000 leukocytes. RESULTS A total of 144 patients were included between June 1994 and April 1995, of which 137 (95%) were primary OLTX. The percentage of positive antigenemia and CMV disease was 55 and 8%, respectively. Seventy-eight (54%) patients were protocol-monitored for the entire follow-up (group 1) and received appropriate preemptive therapy, although 66 (46%) patients had protocol violation by having missed blood samples or blood drawn at unscheduled times (group 2). Using Cox's proportional hazards model, patients with a first antigenemia count of >11 leukocytes had a significantly higher rate of CMV disease compared to patients with an antigenemia count < or =11 leukocytes (RR = 7.3, 95% confidence interval = 2.2 to 24.5). In a multivariate Cox regression analysis, adjustments were made to control for: group 1 versus group 2, use of OKT3, and serology risk categories. This analysis showed that the relative rate of CMV disease was still significantly higher among patients with antigenemia count >11 leukocytes (adjusted RR = 4.9, 95% confidence interval = 1.3 to 18.1). The estimated cost of preemptive therapy was less than that of prophylaxis with i.v. (14-day course) or oral (90-day course) ganciclovir. CONCLUSIONS Preemptive therapy guided by pp65 antigenemia is a useful and cost effective strategy for prevention of CMV disease.
A reproducible model of thromboembolic stroke in mice

AN experimental mouse model of thromboembolic stroke is presented, in which standardized fibrin-rich emboli (15 0μm diameter, 1.5 mm or 4 mm length) are injected into the internal carotid artery. Injection of six or eight 1.5 mm clots (corresponding to 0.16 or 0.2 μl clot material) led to a variable decrease in laser Doppler flow (LDF), but did not result in reproducible infarcts of the middle cerebral artery (MCA) territory, as determined by triphenyltetrazolium chloride (TTC) staining 2 4 h after embolization. Injection of ten 1.5 mm clots (0.2 7 μl) or four 4 mm clots (μl), however, caused a persistent LDF decline to about 20–30% of baseline and led to reproducible infarcts covering the entire MCA territory. The method establishes a clinically relevant, reproducible stroke model for the study of molecular mechanisms of ischemic brain injury in genetically engineered mice.
Adult-onset Still disease in a patient with acute hepatitis A.

Adult-onset Still disease (AOSD) is a systemic inflammatory disease characterized by high fever accompanied by systemic manifestations, such as arthralgia, rash, lymphadenopathy, and hepatosplenomegaly. Since the term ‘‘adult-onset Still disease’’ was first used in 1971 by Bywaters, a considerable number of studies have been reported; however, its etiology remains unknown. Infectious triggers postulated to cause AOSD include echo virus, mumps, cytomegalovirus, parainfluenza, Epstein-Barr virus, influenza A, rubella virus, parvovirus B19, and hepatitis B or C. To date, an association with hepatitis Avirus (HAV) has not been reported. We report a case of AOSD in a patient with acute HAV infection.
“Contrecoup” Fracture of the Sternum

There is probably no single explanation for the general improvement. An expanded range of antibiotics and anaesthetics agents has undoubtedly helped, but probably increased understanding of the problem, crystallized by Avery Jones in 1947, has played the most important part. Summary Of 541 cases admitted suffering from gastro-duodenal haemorrhage 488 were due tG acute or chronic peptic ulceration. Of these 488 cases, 97 were treated by emergency operation. The overall mortality was 5.9%. The frequency and timing of emergency surgery are discussed. A frequency of 20% was found in this series. Comparing this with previous series from this hospital, it does not appear that the mortality rate will be reduced by resorting to surgery more often than this. The number of " immediate " operations (within 12 hours of admission) has tended to fall in this hospital, but nevertheless the dangers of delay in severe or repeated haemorrhage are stressed. It is suggested that acute ulceration often occurs in the post-gastrectomy stomach. In this series probably all the post-gastrectomy haemorrhages were from acute rather than chronic recurrent ulceration. It is argued that gastrectomy for haemorrhage from acute ulcers is often illogical and unnecessary.
X chromosome inactivation in the absence of Dicer

Dicer is central to the RNA interference (RNAi) pathway, because it is required for processing of double-stranded RNA (dsRNA) precursors into small RNA effector molecules. In principle, any long dsRNA could serve as a substrate for Dicer. The X inactive specific transcript (Xist) is an untranslated RNA that is required for dosage compensation in mammals. It coats and silences 1 of the 2 X chromosomes in female cells and initiates a chromosomewide change in chromatin structure that includes the recruitment of Polycomb proteins, but it is largely unknown how Xist RNA mediates these processes. To investigate a potential link between the RNAi pathway and X inactivation, we generated and analyzed Dicer-deficient embryonic stem (ES) cells. In the absence of Dicer, coating by Xist RNA, initiation of silencing, and recruitment of Polycomb proteins occur normally. Dicer ablation had modest effects on the steady-state levels of spliced Xist RNA. Together our data indicate that the RNAi machinery is not essential for the initiation of X inactivation.
A multivariate model of ErbB network composition predicts ovarian cancer cell response to canertinib

Identifying the optimal treatment strategy for cancer is an important challenge, particularly for complex diseases like epithelial ovarian cancer (EOC) that are prone to recurrence. In this study we developed a quantitative, multivariate model to predict the extent of ovarian cancer cell death following treatment with an ErbB inhibitor (canertinib, CI‐1033). A partial least squares regression model related the levels of ErbB receptors and ligands at the time of treatment to sensitivity to CI‐1033. In this way, the model mimics the clinical problem by incorporating only information that would be available at the time of drug treatment. The full model was able to fit the training set data and was predictive. Model analysis demonstrated the importance of including both ligand and receptor levels in this approach, consistent with reports of the role of ErbB autocrine loops in EOC. A reduced multi‐protein model was able to predict CI‐1033 sensitivity of six distinct EOC cell lines derived from the three subtypes of EOC, suggesting that quantitatively characterizing the ErbB network could be used to broadly predict EOC response to CI‐1033. Ultimately, this systems biology approach examining multiple proteins has the potential to uncover multivariate functions to identify subsets of tumors that are most likely to respond to a targeted therapy. Biotechnol. Bioeng. 2012;109: 213–224. © 2011 Wiley Periodicals, Inc.
Calcium/calmodulin signaling controls osteoblast growth and differentiation

Ca2+ is a ubiquitous intracellular messenger responsible for controlling numerous cellular processes including fertilization, mitosis, neuronal transmission, contraction and relaxation of muscles, gene transcription, and cell death. At rest, the cytoplasmic Ca2+ concentration [Ca2+]i is approximately 100 nM, but this level rises to 500–1,000 nM upon activation. In osteoblasts, the elevation of [Ca2+]i is a result of an increase in the release of Ca2+ from endoplasmic reticulum and/or extracellular Ca2+ influx through voltage gated Ca2+ channels. Many of the cellular effects of Ca2+ are mediated by the Ca2+ binding protein, calmodulin (CaM). Upon binding up to four calcium ions, CaM undergoes a conformational change, which enables it to bind to specific proteins eliciting a specific response. Calmodulin kinase II (CaMKII) is a major target of the Ca2+/CaM second messenger system. Once bound to Ca2+/CaM, the multimeric CaMKII is released from its autoinhibitory status and maximally activated, which then leads to an intraholoenzyme autophosphorylation reaction. Calcineurin (Cn) is another major target protein that is activated by Ca2+/CaM. Cn is a serine‐threonine phosphatase that consists of a heterodimeric protein complex composed of a catalytic subunit (CnA) and a regulatory subunit (CnB). Upon activation, Cn directly binds to, and dephosphorylates nuclear factor of activated T cells (NFAT) transcription factors within the cytoplasm allowing them to translocate to the nucleus and participate in the regulation of gene expression. This review will examine the potential mechanisms by which calcium, CaM, CaMKII, and Cn/NFAT control osteoblast proliferation and differentiation. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.
Unstable Lysogeny and Pseudolysogeny in Vibrio harveyi Siphovirus-Like Phage 1

ABSTRACT Exposure of Vibrio harveyi (strain VH1114) to V. harveyi siphovirus-like phage 1 (VHS1) resulted in the production of a low percentage of lysogenized clones of variable stability. These were retrieved most easily as small colonies within dot plaques. Analysis revealed that VHS1 prophage was most likely carried by VH1114 as an episome rather than integrated into the host chromosome. In the late exponential growth phase, lysogenized VH1114 continuously produced VHS1 but also gave rise to a large number of cured progeny. The absence of phage DNA in the cured progeny was confirmed by the absence of VHS1 DNA in Southern blot and PCR assays. Curiously, these very stable, cured subclones did not show the parental phenotype of clear plaques with VHS1 but instead showed turbid plaques, both in overlaid lawns and in dot plaque assays. This phenotypic difference from the original parental isolate suggested that transient lysogeny by VHS1 had resulted in a stable genetic change in the cured clones. Such clones may be called pseudolysogens (i.e., false lysogens), since they have undergone transient lysogeny and have retained some resistance to full lytic phage development, despite the loss of viable or detectable prophage.
Histologic changes in clinically normal breasts at postmortem examination.

IN A PREVIOUS publication 1 we reported that severe epithelial hyperplasia of the large ducts was found in 69% of breasts removed for carcinoma and in only 16% of breast tissue diagnosed as "fibrocystic disease. " Having defined and used our own criteria for the micropathological characterization of benign breast changes associated with carcinoma of the breast and "fibrocystic disease" of the breast, it became necessary to ascertain the frequency of these changes in clinically normal breasts. This study was undertaken to determine the breast changes in 100 consecutive autopsies of women 20 years of age and older with clinically normal breasts. Methods and Results This histologic study, as our previous study, evaluated severe epithelial hyperplasia of the large ducts, the small ducts, and the acini. The presence or absence of fibrosis, sclerosing adenosis, papillomas, apocrine changes, and cysts was noted. The detailed criteria for microscopic changes was described in a
Protein modification by the lipid peroxidation product 4‐hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients

We report increased modification of proteins by 4‐hydroxynoneal (HNE), a product of membrane lipid peroxidation, in the lumbar spinal cord of sporadic amyotrophic lateral sclerosis (ALS) patients versus that of neurologically normal controls. By immunohistochemistry, HNE‐protein modification was detected in ventral horn motor neurons, and immunoprecipitation analysis revealed that one of the proteins modified by HNE was the astrocytic glutamate transporter EAAT2. Given that the function of proteins modified by HNE can be severely compromised as previously demonstrated for glutamate transporters in cortical synaptosome preparatations, our findings suggest a scenario in which oxidative stress leads to the production of HNE, impairment of gluatmate transport, and excitotoxic motor neuron degeneration in ALS.
Stop mutations in exon 6 of the choroideremia gene, CHM, associated with preservation of the electroretinogram.

1. Rosenblatt DS, Aspler AL, Shevell MI, Fenton WA, Seashore MR. Clinical heterogeneity and prognosis in combined methylmalonic aciduria and homocystinuria (cblC). J Inherit Metab Dis. 1997;20:528-538. 2. Robb RM, Dowton SB, Fulton AB, Levy HL. Retinal degeneration in B12 disorder associated with methylmalonic aciduria and sulfur amino acid abnormalities. Am J Ophthalmol. 1984; 97:691-696. 3. Cooper LL, Hansen RM, Darras BT, et al. Rod photoreceptor function in children with mitochondrial disorders. Arch Ophthalmol. 2002; 120:1055-1062. 4. Fulton AB, Hansen RM. The development of scotopic sensitivity. Invest Ophthalmol Vis Sci. 2000; 41:1588-1596. 5. Fulton AB, Hansen R, Westall CA. Development of ERG responses: the ISCEV rod, maximal and cone responses in normal subjects. Doc Ophthalmol. 2003;107:235-241.