Miracle-dz/UniFAR-FTUs huggingface dataset:
Successful engraftment following allogeneic stem cell transplantation with busulfan as a

Busulfan, a sulfonic acid ester, is an alkylating agent with potent toxicity for hematopoietic and sinusoidal endothelial cells. The drug was initially introduced in 1952, as a treatment modality for patients with chronic myeloid leukemia. It was only around 20 years later that this agent was first used as part of the conditioning regimen in bone marrow transplantation, substituting total body irradiation. Considering the fact that busulfan was considered as a potent myeloablative rather than immunosuppressive agent, most transplant centers used the combination of busulfan and cyclophosphamide or other alkylating agents or total body irradiation with the aim of accomplishing maximal myeloablation as well as optimal immunosuppression prior to transplantation of allogeneic stem cells. Since then, the use of busulfan spread widely and it was also used in conjunction with autologous stem cell transplantation (SCT). However, it was soon discovered that the use of busulfan could be associated with hepatic toxicity, mainly veno-occlusive disease, especially in patients undergoing allogeneic SCT. Other toxicities of the drug included electroencephalographic abnormalities and an increased risk of convulsions due to the drug penetrating into the central nervous system, inhibition of stromal cell function, occasional pulmonary toxicity and an association with increased transplant-related mortality when used at high doses for allogeneic SCT. In recent years, busulfex, an intravenous preparation of busulfan, has gradually been replacing oral busulfan in SCT regimens. Its main advantages are reduced liver toxicity and dosage assurance with predictable pharmacokinetics. Given its known myeloablative properties, busulfan was considered in many centers as the treatment of choice for myeloid disorders, however, busulfan, was never recommended as a suitable single agent in a preparative regimen for allogeneic SCT because of its limited toxicity to mature lymphocytes. Combinations of busulfan with cyclophosphamide or other All authors from the Department of Bone Marrow Transplantation & Cancer Immunotherapy, Hadassah-Hebrew University Medical Center Jerusalem 91120, Israel.
Alcohol consumption and smoking and their associations with socio-demographic characteristics, dietary patterns, and perceived academic stress in Puerto Rican college students.

OBJECTIVE College students often use different strategies, such as consuming alcohol and smoking, to cope with stress. We examined the associations between self-perceived academic stress, alcohol consumption, smoking, and dietary patterns in graduate students. METHODS A representative stratified sample of 275 students from each school of the Medical Science Campus of the University of Puerto Rico (UPR-MSC) completed a 48-item questionnaire that solicited the following: socio-demographic data, estimates of self-perceived stress, estimates of the frequency of alcohol consumption and the type(s) of alcohol consumed, details regarding smoking habits, and information associated with diet (i.e., dietary patterns). Fisher's exact test and the Chi2 test were used to assess the associations between the different study variables. RESULTS Only 3% were considered smokers (defined as > 1 cigarettes per day), with the greatest number of smokers among those aged 21-30 y (p<0.05). Smoking habits was not associated with academic load/stress or with dietary pattern. Most smokers reported that their main reason for using cigarettes was to cope with stress. About 70% of the students were considered drinkers (defined as > 0 drink/day), with a higher proportion found among women (63.5%), among those aged 21-30 years (90.6%), and among those with a low or moderate household income (p<0.05). Alcohol intake was significantly associated with academic stress, with a greater proportion of drinkers reporting experiencing moderate levels of academic stress (p<0.05), but it was not associated with dietary patterns or academic load (p>0.05). Most subjects classified as drinkers reported that alcohol consumption was not (in their experience) an effective strategy for the management of stress (81%). CONCLUSION Alcohol consumption was only associated with academic stress. No associations were found between smoking habits and academic stress/load and dietary patterns.
Oral Immunization with Recombinant Lactobacillus acidophilus Expressing espA-Tir-M Confers Protection against Enterohemorrhagic Escherichia coli O157:H7 Challenge in Mice

Enterohemorrhagic Escherichia coli O157:H7 (EHEC O157:H7) causes hemorrhagic colitis and the formation of characteristic attaching and effacing (A/E) lesions in humans. Given the severe sequelae of EHEC O157:H7 infection, it is critical to develop effective vaccines for human use. However, for achieving this goal many hurdles need to be addressed, such as the type or subset of antigens, adjuvant, and the delivery route. We developed a candidate vaccine by inserting the bivalent antigen espA-Tir-M composed of espA and the Tir central domain into Lactobacillus acidophilus. The recombinant L. acidophilus (LA-ET) was safe in a cell model and excluded EHEC O157:H7 from LoVo cells at rates of nearly 94 and 60% in exclusion and competition assays, respectively. LA-ET inhibited the induction of A/E lesions by EHEC O157:H7 cells in vitro. Oral immunization with LA-ET induced higher levels of specific mucosal and systemic antibody responses in mice. Moreover, LA-ET enhanced interferon-γ and interleukin-4 and -10 production, which was associated with mixed helper T (Th1/Th2) cell responses, and protected against EHEC O157:H7 colonization and infection in mice at a rate of 80%. Histopathological analyses revealed that orally administered LA-ET reduced or inhibited A/E lesions and toxin-induced systemic injury. These findings demonstrate that LA-ET induces both humoral and cellular immune responses in mice and is therefore a promising vaccine against EHEC O157:H7 infection.
Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease.

BACKGROUND Pulmonary rehabilitation has become a cornerstone in the management of patients with stable Chronic Obstructive Pulmonary Disease (COPD). Systematic reviews have shown large and important clinical effects of pulmonary rehabilitation in these patients. In unstable COPD patients who have suffered from an exacerbation recently, however, the effects of pulmonary rehabilitation are less established. OBJECTIVES To assess the effects of pulmonary rehabilitation after COPD exacerbations on future hospital admissions (primary outcome) and other patient-important outcomes (mortality, health-related quality of life and exercise capacity). SEARCH STRATEGY Trials were identified from searches of CENTRAL, MEDLINE, EMBASE, PEDRO and the Cochrane Central Register of Controlled Trials. Searches were current as of July 2008. SELECTION CRITERIA Randomized controlled trials comparing pulmonary rehabilitation of any duration after exacerbation of COPD with conventional care. Pulmonary rehabilitation programmes needed to include at least physical exercise. Control groups received conventional community care without rehabilitation. DATA COLLECTION AND ANALYSIS We calculated pooled odds ratios and weighted mean differences (WMD) using fixed-effects models. We requested missing data from the authors of the primary studies. MAIN RESULTS We identified six trials including 219 patients. Pulmonary rehabilitation significantly reduced hospital admissions (pooled odds ratio 0.13 [95% CI 0.04 to 0.35], number needed to treat (NNT) 3 [95% CI 2 to 4], over 34 weeks) and mortality (pooled odds ratio 0.29 [95% CI 0.10 to 0.84], NNT 6 [95% CI 5 to 30] over 107 weeks). Effects of pulmonary rehabilitation on health-related quality of life were well above the minimal important difference (weighted mean differences for dyspnea, fatigue, emotional function and mastery domains of the Chronic Respiratory Questionnaire between 1.15 (95% CI: 0.94, 1.36) and 1.88 (95% CI:1.67, 2.09) and between -9.9 (95% CI:-18.05, -1.73) and -17.1 (95% CI: -23.55, -10.68) for total, impact and activity limitation domains of the St. Georges Respiratory Questionnaire). In all trials, pulmonary rehabilitation improved exercise capacity (60-215 meters in six-minute or shuttle walk tests). No adverse events were reported (two studies). AUTHORS' CONCLUSIONS Evidence from small studies of moderate methodological quality suggests that pulmonary rehabilitation is a highly effective and safe intervention to reduce hospital admissions and mortality and to improve health-related quality of life in COPD patients after suffering an exacerbation.
Transcutaneous electrical nerve stimulation following appendicectomy: the placebo effect.

Abstract A controlled trial was undertaken to compare the efficacy of transcutaneous electrical nerve stimulation (TENS) with standard intramuscular opiate analgesia in the management of postoperative pain following appendicectomy. Consecutive patients undergoing emergency appendicectomy were randomised into control, sham TENS and active TENS groups. There was a significant decrease in pain severity and analgesic intake in both active and sham TENS groups when compared with the control group (P less than 0.01). No difference was demonstrated in pain severity between active and sham TENS groups but the active TENS group required slightly less analgesia. These results suggest that the major benefit of TENS in the postappendicectomy patient is due to its 'placebo effect' and its use in this situation cannot be recommended.
Westerdykella reniformis sp. nov., producing the antibiotic metabolites melinacidin IV and chetracin B

Westerdykella reniformis Ebead & Overy sp. nov. is described based on morphology and phylogenetic analyses using ITS, nLSU rDNA, and β-tubulin gene sequences. Westerdykella reniformis is characterized by the production of cleistothecioid ascomata, containing small globose to subglobose asci with 32, aseptate, dark colored, pronouncedly reniform ascospores having a concave central groove. The isolate was obtained from a red alga (Polysiphonia sp.) collected from the tidal zone in Canada at low tide. Organic extracts enriched in extrolites, obtained from fermentation on a rice-based media, inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), S. warneri, and Proteus vulgaris. Presented here is the identification of the compounds responsible for the observed antimicrobial activity, the taxonomic description of W. reniformis, and a dichotomous key to the known species of Westerdykella based on macro- and micromorphological characters.
Effects of long‐term low oxygen tension in human chondrosarcoma cells

The cell‐based therapies could be potential methods to treat damaged cartilage tissues. Instead of native hyaline cartilage, the current therapies generate mainly weaker fibrocartilage‐type of repair tissue. A correct microenvironment influences the cellular phenotype, and together with external factors it can be used, for example, to aid the differentiation of mesenchymal stem cells to defined types of differentiated adult cells. In this study, we investigated the effect of long‐term exposure to 5% low oxygen atmosphere on human chondrosarcoma HCS‐2/8 cells. This atmosphere is close to normal oxygen tension of cartilage tissue. The proteome was analyzed with label‐free mass spectrometric method and further bioinformatic analysis. The qRT‐PCR method was used to gene expression analysis, and ELISA and dimethylmethylene blue assays for type II collagen and sulfated glycosaminoglycan measurements. The 5% oxygen atmosphere did not influence cell proliferation, but enhanced slightly ACAN and COL2A1 gene expression. Proteomic screening revealed a number of low oxygen‐induced protein level responses. Increased ones included NDUFA4L2, P4HA1, NDRG1, MIF, LDHA, PYGL, while TXNRD1, BAG2, TXN2, AQSTM1, TNFRSF1B, and EPHX1 decreased during the long‐term low oxygen atmosphere. Also a number of proteins previously not related to low oxygen tension changed during the treatment. Of those S100P, RPSS26, NDUFB11, CDV3, and TUBB8 had elevated levels, while ALCAM, HLA‐B, EIF1, and ACOT9 were lower in the samples cultured at low oxygen tension. In conclusion, low oxygen condition causes changes in the cellular amounts of several proteins.
Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors

The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation. SOX10 and melanocytic markers were negative in all cases tested. In contrast, a control group of classic LPF displayed bland, monomorphic histology and lacked S100 protein immunoreactivity. To define the pathogenetic abnormalities in these seemingly distinctive groups, we performed RNA sequencing for fusion gene discovery in 2 cases each, followed by screening for any novel alterations identified in a larger cohort representing both entities. The 2 index LPF-like neural tumors (LPF-NT) showed TPR-NTRK1 and TPM3-NTRK1 gene fusions, which were further validated by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Subsequent FISH screening of 14 LPF-NT identified recurrent NTRK1 gene rearrangements in 10 (71%) cases. Of the NTRK1-negative LPF-NT cases, 1 case each showed ROS1 and ALK gene rearrangements. In contrast, none of the 25 classic LPFs showed NTRK1 gene rearrangements, although regional abnormalities were noted in the 1q21-22 region by FISH in a majority of cases. Furthermore, NTRK1 immunostaining was positive only in NTRK1-rearranged S100-positive LPF-NT but negative in classic LPF. These results suggest that NTRK1 oncogenic activation through gene fusion defines a novel and distinct subset of soft tissue tumors resembling LPF, but displaying cytologic atypia and a neural immunophenotype, provisionally named LPF-like neural tumors.
Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives

Almost 25 years after the first report that glutamate can activate receptors coupled to heterotrimeric G-proteins, tremendous progress has been made in the field of metabotropic glutamate receptors. Now, eight members of this family of glutamate receptors, encoded by eight different genes that share distinctive structural features have been identified. The first cloned receptor, the metabotropic glutamate (mGlu) receptor mGlu1 has probably been the most extensively studied mGlu receptor, and in many respects it represents a prototypical subtype for this family of receptors. Its biochemical, anatomical, physiological, and pharmacological characteristics have been intensely investigated. Together with subtype 5, mGlu1 receptors constitute a subgroup of receptors that couple to phospholipase C and mobilize Ca2+ from intracellular stores. Several alternatively spliced variants of mGlu1 receptors, which differ primarily in the length of their C-terminal domain and anatomical localization, have been reported. Use of a number of genetic approaches and the recent development of selective antagonists have provided a means for clarifying the role played by this receptor in a number of neuronal systems. In this article we discuss recent advancements in the pharmacology and concepts about the intracellular transduction and pathophysiological role of mGlu1 receptors and review earlier data in view of these novel findings. The impact that this new and better understanding of the specific role of these receptors may have on novel treatment strategies for a variety of neurological and psychiatric disorders is considered.
Comparative Effectiveness and Safety of Monodrug Therapies for Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia

AbstractA wide array of drugs are available for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH), but the evidence for the comparative effectiveness is controversial.The objective of this study is to evaluate the comparative effectiveness and safety of monodrug therapies for BPH.Data sources are MEDLINE, EMBASE, and the Cochrane Library.We included randomized controlled trials that compared &agr;-blockers, 5-alpha reductase inhibitors (5ARIs), muscarinic receptor antagonists (MRAs), phosphodiesterase-5 inhibitor (PDE5-Is), or placebo for the treatment of BPH.Comparative effectiveness and safety were pooled by both traditional meta-analysis and network meta-analysis. Summary effect size was calculated as mean difference (MD) and relative risk (RR), together with the 95% confidence intervals (CIs). This study included 58,548 participants from 124 trials in total. When compared with placebo, &agr;-blockers, 5ARIs, and PDE5-Is reduced International Prostate Symptom Score (IPSS) by −1.35 to −3.67 points and increased peak urinary flow rate (PUF) by −0.02 to 1.95 mL/s, with doxazosin (IPSS: MD, −3.67[−4.33 to −3.02]; PUF: MD, 1.95[1.61 to 2.30]) and terazosin (IPSS: MD, −3.37 [−4.24 to −2.50]; PUF: MD, 1.21[0.74 to 1.66]) showing the greatest improvement. The improvement in the IPSS was comparable among tamsulosin, alfuzosin, naftopidil, silodosin, dutasteride, sildenafil, vardenafil, and tadalafil. The incidence of total adverse events and withdraws due to adverse events were generally comparable among various agents.In conclusion, &agr;-blockers, 5ARIs, and PDE5-Is are effective for BPH, with doxazosin and terazosin appearing to be the most effective agents. Drug therapies for BPH are generally safe and well-tolerated, with no major difference regarding the overall safety profile.
Properties of Local Nondeterminism of Gaussian and Stable Random Fields and Their Applications

In this survey, we flrst review various forms of local nondeterminism and sectorial local nondeterminism of Gaussian and stable random flelds. Then we give su‐cient conditions for Gaussian random flelds with stationary increments to be strongly locally nondeterministic (SLND). Finally, we show some applications of SLND in studying sample path properties of (N;d)-Gaussian random flelds. The class of random flelds to which the results are applicable includes fractional Brownian motion, the Brownian sheet, fractional Brownian sheets and so on. Running head: Local Nondeterminism of Gaussian Random Fields 2000 AMS Classiflcation Numbers: Primary 60G15, 60G17, 60G60. Secondary 60G18, 28A80, 28A78.
Computational Biology Resources Lack Persistence and Usability

Innovation in computational biology research is predicated on the availability of published methods and computational resources. These resources facilitate the generation of new hypotheses and observations both on the part of the creators and the scientists who use them. These methods and resources include Web servers, databases, and software, both complex and simple, that implement a specific procedure or algorithm. Usually, a resource is maintained by the laboratory in which it was initially developed. We would assert that there is a growing level of frustration among scientists who attempt to use many of these resources and find that they no longer exist or are not properly maintained. Whether you agree or disagree with this statement and the evidence that follows, we welcome your thoughts and invite you to add a Comment to this article to share your own experiences and perspectives. It is timely to visit this situation in more detail. The International Society for Computational Biology (ISCB) is reviewing its position on software sharing, and this journal is now doing the same (the views expressed here are not necessarily those of the journal—this is a personal perspective and not an editorial). To help us gain a better understanding of the resource situation, we took on two simple experiments: first, a review of the persistence of Web servers, and, second, an experience creating a metaserver—a Web site where users can come and run a variety of methods to compare results. Here is what we found.
Speech Recognition as Feature Extraction for Speaker Recognition

Information from speech recognition can be used in various ways in state-of-the-art speaker recognition systems. This includes the obvious use of recognized words to enable the use of text-dependent speaker modeling techniques when the words spoken are not given. Furthermore, it has been shown that the choice of words and phones itself can be a useful indicator of speaker identity. Also, recognizer output enables higher-level features, in particular those related to prosodic properties of speech. Finally, we discuss the use of mere by-products of word recognition, such as subword unit alignments, pronunciations, and speaker adaptation transforms to derive powerful nonstandard features for speaker modeling. We present specific techniques and results from SRI's NIST speaker recognition evaluation system.
Serum levels of Th2 chemokines, CCL17, CCL22, and CCL27, were the important markers of severity in infantile atopic dermatitis

Atopic dermatitis (AD) is considered to be Th2 cell‐mediated disorder. In most infants with AD, AD may be induced by food allergy. In the early stage of infantile AD, it is unclear whether there are changes in serum Th2 chemokines or in Th2 chemokine production by peripheral blood mononuclear cells (PBMC). Thirty‐four patients with AD were examined (mean age, 4.5 months; female:male, 18:16). Ten age‐matched infants with no history of allergic disease were used as controls. Thirty of these 34 patients were sensitized with ovalbumin (OVA; radioallergrosolvent score of >2). Serum levels of CCL17, CCL22, and CCL27 were measured with enzyme‐linked immunosolvent assay (ELISA) kits and their correlation with the severity of skin lesions, defined by the scoring atopic dermatitis (SCORAD) index, was analyzed. The amounts of TNF‐α, CCL17, CCL22, and CCL27 in the culture supernatants of PBMC from OVA‐sensitized AD infants after stimulation with OVA were estimated with ELISA kits. Elevated serum CCL17, CCL22, and CCL27 levels significantly correlated with SCORAD index (r = 0.7181, p < 0.001; r = 0.5354, p < 0.005; r = 0.8312, p < 0.0001, respectively). CCL22 levels produced by PBMC from OVA‐sensitized infants with AD reflected serum CCL22 levels. Only six of 30 OVA‐sensitized patients in whom the skin signs increased immediately after OVA intake showed markedly high titers of TNF‐α produced by PBMC after stimulation with OVA. These high TNF‐α titers correlated significantly with serum CCL27 levels (r = 0.7181, p < 0.001). Serum concentrations of CCL17, CCL22, and CCL27 correlate well with the extent and intensity of AD in infants. Of the three Th2 chemokines examined, serum CCL27 correlated most significantly with the severity of AD. Thus, the peripheral immune responses of infantile AD patients are skewed to a Th2 dominant bias.