Miracle-dz/UniFAR-FTUs huggingface dataset:
Ibrutinib for the treatment of chronic lymphocytic leukemia

Introduction: Chemoimmunotherapy has improved response rates and overall survival (OS) in patients with chronic lymphocytic leukemia (CLL). Despite these advances, CLL remains an incurable disease outside of stem cell transplantation. B-cell receptor (BCR) signaling is a pivotal pathway in the pathogenesis of CLL by promoting survival and proliferation of CLL cells. Bruton's tyrosine kinase (BTK) is essential for BCR signaling and can be irreversibly inhibited by ibrutinib (PCI 32765). Areas covered: The clinical presentation and current treatment of CLL are briefly reviewed before focusing on the role of BCR signaling in the pathogenesis of CLL. The development of ibrutinib and the preclinical and clinical experience with this targeted agent in CLL are discussed. Expert opinion: Ibrutinib and other kinase inhibitors targeting BCR signaling are heralding a new era in the treatment of CLL. Efficacy and tolerability of ibrutinib are equally impressive and make it the most active monotherapy in CLL. Ibrutinib does not appear to increase the risk of infections, and the development of drug resistance is uncommon, providing a foundation for possible long-term therapy with this agent. Treatment goals and strategies will become more evident as we learn more about duration of response, mechanisms of resistance, tolerability of chronic use, and results with combination therapies.
Diagnosis and management of motor neurone disease

Motor neurone disease is a devastating illness which leads to progressive paralysis and eventual death. We will discuss the presentation of motor neurone disease in primary care and update non-specialists on progress with regards to life prolonging interventions, better control of disease symptoms, and an increased understanding of disease mechanisms. Motor neurone disease is rare but patients often are aware of it, so this review should help non-specialists reassure patients in whom it is unlikely to be the diagnosis.
Should we screen for abdominal aortic aneurysm? Yes

In January, the government announced five pilot screening programmes for aortic aneurysm in men aged 65 in England. Stephen Brearley describes the rationale for this proposal while James Johnson (doi: 10.1136/bmj.39514.494167.AD) argues that it is not without pitfalls
Effects of SDF-1α/CXCR4 on vascular smooth muscle cells and bone marrow mesenchymal cells in a rat carotid artery balloon injury model

Summary Bone marrow mensenchyme cells (BMSCs) can differentiate into endothelial progenitor cells which then migrate to injured sites for the repair of neointima, and stromal cell-derived factor-1α (SDF-1α) can mediate the migration of CXCR4 expressing stem/progenitor cells to injured sites for pair. Protein and mRNA expression of SDF-1α and CXCR4 were determined by RT-PCR, Western blot and ELISA. Immediately after common carotid artery balloon injury, the mRNA expression of SDF-1α in vascular smooth muscle cells (VSMCs) first increased and then decreased 7 days later. VSMCs transfected with SDF-1α siRNA did not express SDF-1α mRNA, but after transfection with SDF-1α siRNA, the SDF-1α content in injured VSMCs gradually returned to the baseline level. Normal BMSCs rarely expressed CXCR4 mRNA, but the CXCR4 mRNA expression on BMSCs increased significantly 4 days after common carotid artery injury and was maintained. The migration of BMSCs after artery injury was enhanced when compared with normal BMSCs, but SDF-1α siRNA transfection of VSMCs and AMD3100 treatment remarkably decreased the chemotaxis of BMSCs to VSMCs and SDF-1α, respectively. We conclude that the SDF-1α/CXCR4 axis plays an important role in the migration of BMSCs after balloon injury and can ultimately cause abnormal proliferation of the intima.
Synergistic antinociceptive interaction between aspirin and tramadol, the atypical opioid analgesic, in the rat

In order to assess a possible synergistic antinociceptive interactions, the analgesic effects of aspirin per s̀s (acetyl salicylic acid or “ASA”), a nonsteroidal anti‐inflammatory drug (NSAID), and tramadol s.c. (TRA), an atypical opioid analgesic, administered either separately or in combination were determined in a model of pain‐induced functional impairment in the rat, groups of six rats received either vehicle, ASA (175.4, 312.1, 555.1, 987.0, 1, 755.3, or 3, 121.2 μmol/kg) and TRA (21.3, 38.0, 67.5, 120.0, or 213.5 μmol/kg), or a combination of ASA and TRA (24 different combinations). This allowed us to detect the interaction profile of these combinations. The ED50 for either ASA or TRA were 1, 173.5 ± 7.4 μmol/kg and 141.5 ± 6.8 μmol/kg, respectively. The data obtained confirmed an interaction between ASA and TRA and showed antinociception that may be additive or synergistic, depending on the drug ratio administered. Furthermore, eight combinations showed various degrees of potentiation (P < .01), whereas the others (16) exhibited analgesic effects not different from that of ASA alone. The combination of ASA (3, 121.2 μmol/kg) and TRA (120.0 μmol/kg) produced the maximum analgesic effect. However, the combination of ASA (987/ μmol/kg) with TRA (120.0 μmo/kg) produced the highest potentiation effects. This study clearly showed (1) that there is an interaction between ASA and TRA and (2) which combination of these analgesic drugs produced either the maximum analgesic effect or the highest degree of potentiation in the rat. © 1995 Wiley‐Liss, Inc.
Music identification skills of children with specific language impairment.

BACKGROUND To date very few studies have investigated the musical skills of children with specific language impairment (SLI). There is growing evidence that SLI affects areas other than language, and it is therefore reasonable to hypothesize that children with this disorder may have difficulties in perceiving musical stimuli appropriately. AIMS To compare melody and song identification skills in a group of children with SLI and in a control group of children with typical language development (TD); and to study possible correlations between music identification skills and language abilities in the SLI group. METHODS & PROCEDURES This is a prospective case control study. Two groups of children were enrolled: one meeting DSM-IV-TR(®) diagnostic criteria for SLI and the other comprising an age-matched group of children with TD. All children received a melody and a song identification test, together with a test battery assessing receptive and productive language abilities. OUTCOMES & RESULTS 30 children with SLI (mean age = 56 ± 9 months) and 23 with TD (mean age = 60 ± 10 months) were included. Melody and song identification scores among SLI children were significantly lower than those of TD children, and in both groups song identification scores were significantly higher than melody identification scores. Song identification skills bore a significant correlation to chronological age in both groups (TD: r = 0.529, p = 0.009; SLI: r = 0.506, p = 0.004). Whereas no other variables were found explaining the variability of melody or song identification scores in either group, the correlation between language comprehension and song identification in the SLI group approached significance (r = 0.166, p = 0.076). CONCLUSIONS & IMPLICATIONS The poorer music perception skills of SLI children as compared with TD ones suggests that SLI may also affect music perception. Therefore, training programmes that simultaneously stimulate via language and music may prove useful in the rehabilitation of children affected by SLI.
Avaliação morfométrica do tendão de Aquiles por ultra-sonografia

OBJETIVO: Determinar os valores normais dos diâmetros ântero-posterior e transversal do tendao de Aquiles na nossa populacao e correlaciona-los com sexo, faixa etaria, cor da pele, grupo sanguineo ABO e indice de massa corporal. MATERIAIS E METODOS: Foi feita analise ultra-sonografica de 100 tendoes de Aquiles de 50 voluntarios sadios, visando a mensuracao dos diâmetros ântero-posterior e transversal desses tendoes. Todos os exames foram realizados pelo mesmo examinador, em aparelho de ultra-sonografia com transdutor linear com frequencia de 10 MHz. RESULTADOS: Dos 50 voluntarios estudados, 25 eram do sexo masculino e 25, do sexo feminino, com a faixa etaria variando de 20 a 52 anos (media de 33,9 anos). O valor medio do diâmetro transversal do tendao de Aquiles foi de 13,3 ± 1,0 mm para o sexo feminino e 14,4 ± 1,4 mm para o sexo masculino; em relacao ao diâmetro ântero-posterior, foi de 5,4 ± 0,5 mm para o sexo feminino e 5,6 ± 0,6 mm para o sexo masculino. Os diâmetros do tendao de Aquiles foram significativamente menores no sexo feminino (p < 0,05). Nao houve diferenca estatisticamente significativa entre os diâmetros ântero-posterior e transversal em relacao a faixa etaria, grupo sanguineo e cor da pele. O grupo com indice de massa corporal de sobrepeso apresentou diâmetro transversal do tendao de Aquiles significativamente maior que do grupo com indice de massa corporal normal. CONCLUSAO: Os valores medios encontrados na nossa casuistica foram discordantes em relacao a maioria dos estudos da literatura, demonstrando ser de grande importância a padronizacao e o emprego de tabelas proprias da nossa populacao na pratica clinica diaria.
Effects of yoga on tension headache

Background: Stress is an important triggering factor for tension headache. Yoga is one of the effective therapies in reducing stress levels. Studies had shown that shavasana is as effective as electromyography (EMG) biofeedback in reduction of tension headache. Aim: The aim of this study is to evaluate effect of yoga, namely yoga asana and relaxation technique on tension headache. Materials and Methods: Thirty patients diagnosed to have tension headache according to the International Headache Society Criteria II were included in this study. Patients were subjected daily to one yoga session for 1 month. Headache intensity by visual pain analogue scale (VAS) was assessed before and after yoga. Results: There was a significant reduction in VAS after yoga therapy. This study shows that yoga is beneficial in reduction of stress levels thereby reduction in tension headache. Conclusions: The results of this study suggest that yoga has a potential beneficial role in treatment for tension type headache. Further, larger studies are required to substantiate its benefits.
EEG-NeXt: A Modernized ConvNet for The Classification of Cognitive Activity from EEG

One of the main challenges in electroencephalogram (EEG) based brain-computer interface (BCI) systems is learning the subject/session invariant features to classify cognitive activities within an end-to-end discriminative setting. We propose a novel end-to-end machine learning pipeline, EEG-NeXt, which facilitates transfer learning by: i) aligning the EEG trials from different subjects in the Euclidean-space, ii) tailoring the techniques of deep learning for the scalograms of EEG signals to capture better frequency localization for low-frequency, longer-duration events, and iii) utilizing pretrained ConvNeXt (a modernized ResNet architecture which supersedes state-of-the-art (SOTA) image classification models) as the backbone network via adaptive finetuning. On publicly available datasets (Physionet Sleep Cassette and BNCI2014001) we benchmark our method against SOTA via cross-subject validation and demonstrate improved accuracy in cognitive activity classification along with better generalizability across cohorts.
Tumor angiogenesis and endometrial cancer

Increasing importance is given to the clinical significance of the new formation of vessels (angiogenesis) in the course of physiological inflammatory and neoplastic processes. Angiogenesis is best studied in the growth of malignant tumors, since cancer may be regarded as the most important angiogenesis-dependent disease. Vascular endothelial cell proliferation, migration, and capillary formation are stimulated by angiogenic growth factors, which include the proteins vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor, and eicosanoids synthesized from n-6 fatty acids. Angiogenesis plays an important role in physiological proliferation of the endometrium and formation of corpus luteum in the second half of menstrual cycle. The present study showed that microvessel counts affect prognosis of patients with endometrial cancer. Analysis of angiogenesis in endometrial cancer may be a useful biologic parameter and additional study of neovascularization is required. Tumor angiogenesis is regulated by the balance of stimulators (e.g., VEGF, bFGF) and inhibitors of angiogenesis (e.g., angiostatin, endostatin, angiostatic steroids). Measuring angiogenesis (blood vessel density) and/or its main regulators such as VEGF and bFGF in solid tumors, or the levels of these growth factors in the serum or urine provides new and sensitive markers for tumor progression, metastasis and prognosis.
Detection of Vibrio parahaemolyticus, Vibrio vulnificus and Vibrio cholerae with respect to seasonal fluctuations in temperature and plankton abundance.

Over a 1-year period, bi-monthly estuarine surface water and plankton samples (63-200 and > 200 μm fractions) were assayed by polymerase chain reaction for the prevalence of total Vibrio parahaemolyticus, V. vulnificus and V. cholerae and select genes associated with clinical strains found in each species. Neither temperature nor plankton abundance was a significant correlate of total V. parahaemolyticus; however, the prevalence of genes commonly associated with clinical strains (trh, tdh, ORF8) increased with temperature and copepod abundance (P < 0.05). The prevalence of total V. vulnificus and the siderophore-related viuB gene also increased with temperature and copepod and decapod abundance (P < 0.001). Temperature and copepod abundance also covaried with the prevalence of V. cholerae (P < 0.05), but there was no significant relationship with ctxA or other genes commonly found in clinical strains. Results show that genes commonly associated with clinical Vibrio strains were more frequently detected in association with chitinous plankton. We conclude that V. parahaemolyticus, V. vulnificus, V. cholerae and subpopulations that harbour genes common to clinical strains respond distinctly to seasonal changes in temperature as well as shifts in the taxonomic composition of discrete plankton fractions.
Effects of 2‐(1‐hydroxypentyl)‐benzoate on platelet aggregation and thrombus formation in rats

2‐(1‐hydroxypentyl)‐benzoate (dl‐PHPB), a derivate of 3‐n‐butylphthalide (NBP), is a novel therapeutic agent for treatment of cerebral ischemia. In the present study, the antiplatelet and antithrombotic activities of dl‐PHPB were evaluated in ex vivo platelet aggregation and in vivo arteriovenous (A‐V) shunt models. dl‐PHPB inhibited platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid (AA), and collagen (COL) in a dose‐dependent manner when given orally (12.9–129.5 mg/kg). The inhibitory potency was similar to 3‐n‐butylphthalide (NBP) and aspirin (ASP). Inhibition on platelet aggregation was also observed after iv administration of dl‐PHPB (1.29–12.9 mg/kg). The time‐course of these effects showed the maximal inhibition on platelet aggregation at 1 h after oral administration and 30 min after iv injection. dl‐PHPB (12.9–129.5 mg/kg, p.o.) caused dose‐dependent inhibition of thrombus formation in the rat A‐V shunt thrombosis model. These results show that dl‐PHPB is an orally and iv antiplatelet and antithrombotic agent and may be useful for treatment of ischemia stroke. Drug Dev Res 63:174–180, (2004). © 2004 Wiley‐Liss, Inc.
t(X;14)(p22;q32)/t(Y;14)(p11;q32) CRLF2-IGH translocations from human B-lineage ALLs involve CpG-type breaks at CRLF2, but CRLF2/P2RY8 intrachromosomal deletions do not.

To the editor: Rearrangements involving the type I cytokine receptor subunit CRLF2 occur in 5% to 7% of all adult and pediatric B-cell precursor acute lymphoblastic leukemias (B-ALL) and in 60% of B-ALL in children with Down syndrome. [1][1]–[4][2] CRLF2 rearrangement places full-length CRLF2
Hope in Multiple Sclerosis: A Nursing Perspective

Abstract Feelings of hopelessness are common in patients with multiple sclerosis (MS), which poses a significant threat to an individual's independence and feelings of competence. Because hope has been shown to play an important role in health and coping during chronic illness, it is critical for the MS provider to understand the elements of hope and recognize when the person with MS is struggling with feelings of hopelessness. The MS nurse is the pivotal player in ensuring that the individual with MS maintains a sense of hope throughout the illness. In addition to providing education, counseling and referrals, the nurse can help the MS patient focus on feelings and ideas, recognize personal reasons for living, and establish both short-term and long-term goals.
A Comparative Physiochemical Properties of Esomeprazole Brands

Esomeprazole is the S-isomer of Omeprazole and it is a proton pump inhibitor (PPI). Esomepra-zole is used in acid-related disorders and it is available as several brands in the market which makes it difficult for doctors to select the effective, safe and economic one for patients. Therefore we have decided to establish pharmaceutical equivalence among the different brands of esomeprazole available in Karachi, Pakistan. In our present study different brands of esomeprazole are evaluated for weight variation, hardness and dissolution. Disintegration Test shows results for NEX 01, ESS 02, EZI 03 and they disintegrate in 1.35, 1.15 and 2.15 minutes respectively. Dissolution test demonstrate the result as NEX 01, ESS 02, EZI 03 is 100.00% for NEX, 117.87% for ESS and 80.66%. The results showed that all parameters weight-variation, hardness, dissolution of different brands of esomeprazole are in accordance with the USP limits.
Change of TGF-β1 concentration in blood serum of patients during systemic treatment of severe psoriasis

Change of TGF-β1 concentration in blood serum of patients during systemic treatment of severe psoriasis TGF-β1 is a growth factor with multiple actions, responsible for many pathological and physiological processes. Radiation of the skin with a narrowband 311 nm UVB light source is the most often used method of therapy in psoriasis treatment. The aim of the study was to compare different therapy methods on the change of TGF-β1 serum concentration during two weeks of treatment. The TGF-β1 concentration in blood serum of patients with psoriasis was statistically significantly lower than in the control group. For psoriasis treatment, narrow band 311 nm UVB phototherapy was applied to 37 patients and systemic pharmacological treatment with metothrexate, to a group of 18 patients. After two weeks, there was a significant reduction of Psoriasis Area and Severity Index (PASI) and increase of TGF-β1 serum concentration. Narrowband UVB caused a lower PASI, and higher TGF-β1 serum concentration than did pharmacological systemically treatment. Growth factor TGF-β1 had an effect on both of these processes. Lack of TGF-β1 in psoriatic skin is responsible for TH1-induced immune reactions and intensive proliferation of keratinocytes, which are typical of psoriasis. UVB radiation results in a higher TGF-β1 tissue concentration. Elevation of TGF-β1 concentration in blood serum and skin after UVB may present a possible mechanism for the positive effect of UVB in psoriasis treatment. TGF-β1 koncentrācijas pārmaiņas serumā slimniekiem ar smagu psoriāzes norisi ārstēšanas gaitā TGF-β1 ir universāls un plašas darbības spektra augšanas faktors, kurš nosaka daudzas fiziologiskas un patologiskas norises organismā. Traucējumi TGF-1 augšanas faktora darbībā vai tam pakļautajos receptoros un signālmolekulās ir saistīti ar daudzām slimībām, labdabīgu un ļaundabīgu audzēju rašanos, kā arī ar novecošanas procesiem. Ādas apstarošana ar šaura spektra UVB viļņa garumu 311 nm ir viena no visbiežāk lietojamām ārstēšanas metodēm smagas psoriāzes gadījumos. Mūsu pētījuma mērķis bija izvērtēt atšķirīgas iedarbības ārstēšanas metožu ietekmi uz TGF-1 koncentrācijas maiņu serumā slimniekiem ar smagu psoriāzi norisi. TGF-1 koncentrācija asins serumā slimniekiem ar smagu psoriāzi bija statistiski nozīmīgi zemāka salīdzinot ar klīniski veseliem indivīdiem kontrolgrupā. 37 slimniekiem tika nozīmēta 311 nm šaura spektra UVB fototerapija, 18 slimniekiem - farmakologiskā sistēmiskā ārstēšana ar metotreksātu. Pēc divu nedēļu ārstēšanas kursa PASI kritums un TGF-1 seruma koncentrācijas līmeņa palielinājums tika novērots tiem slimniekiem, kuriem tika nozīmēta šaura spektra UVB fototerapija. TGF-1 deficīts psoriātiskā ādā nosaka tai raksturīgo Th1 un Th17 limfocītu nosacītu imūno reakciju attīstību. In vitro ādas apstarošana ar UVB stimulē TGF-1 izstrādi keratinocītos un fibroblastu šūnās. TGF-1 izstrādes stimulācija ir viens no mehānismiem, kādā veidā, izmantojot UVB starojumu, tiek sasniegts ārstnieciskais efekts slimniekiem ar psoriāzi.
A decade of R-CHOP.

Initial results of the first randomized trial evaluating the addition of rituximab to CHOP for DLBCL were reported in December 2000, ushering in the new millennium by delivering on the promise of targeted therapy. [1][1] In this issue of Blood , Coiffier et al—having reached a median follow-up of
Generation of a CRISPR database for Yersinia pseudotuberculosis complex and role of CRISPR-based immunity in conjugation.

The clustered regularly interspaced short palindromic repeat - CRISPR-associated genes (CRISPR-Cas) system is used by bacteria and archaea against invading conjugative plasmids or bacteriophages. Central to this immunity system are genomic CRISPR loci that contain fragments of invading DNA. These are maintained as spacers in the CRISPR loci between direct repeats and the spacer composition in any bacterium reflects its evolutionary history. We analysed the CRISPR locus sequences of 335 Yersinia pseudotuberculosis complex strains. Altogether 1902 different spacer sequences were identified and these were used to generate a database for the spacer sequences. Only ∼10% of the spacer sequences found matching sequences. In addition, surprisingly few spacers were shared by Yersinia pestis and Y. pseudotuberculosis strains. Interestingly, 32 different protospacers were present in the conjugative plasmid pYptb32953. The corresponding spacers were identified from 35 different Y. pseudotuberculosis strains indicating that these strains had encountered pYptb32953 earlier. In conjugation experiments, pYptb32953-specific spacers generally prevented conjugation with spacer-positive and spacer-free strains. However, some strains with one to four spacers were invaded by pYptb32953 and some spacer-free strains were fully resistant. Also some spacer-positive strains were intermediate resistant to conjugation. This suggests that one or more other defence systems are determining conjugation efficiency independent of the CRISPR-Cas system.
Ex vivo maintenance of hematopoietic stem cells by quiescence induction through Fbxw7α overexpression.

Cell-cycle quiescence in hematopoietic stem cells (HSCs) is essential for maintaining stemness by protecting cells from differentiation or senescence. F-box and WD-40 domain protein 7 (Fbxw7) maintains HSCs and suppresses leukemogenesis by mediating ubiquitin-dependent degradation of cell-cycle activators and oncoproteins. Fbxw7α was shown to be the preferentially expressed Fbxw7 isoform in primitive HSCs. Forced Fbxw7α expression in lineage marker Sca-1(+)c-Kit(+) cells led to cell-cycle dormancy by reducing the protein levels of the Fbxw7 substrates c-Myc, Notch1, and phosphorylated S6 (a key downstream element of mTOR). Hypoxia, an essential factor for HSC quiescence, suppressed c-Myc in an Fbxw7α-dependent manner. Fbxw7α-overexpressing lineage marker Sca-1(+)c-Kit(+) cells sustained high reconstitution capacities during in vitro culture. These data suggest that Fbxw7α sustains HSC dormancy through c-Myc, Notch1, and the mTOR pathways. The modulation of Fbxw7α expression or activity represents a promising new tool for ex vivo HSC maintenance.