Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I, multicentre, dose‐escalation trial of monotherapy with milatuzumab (humanized anti‐CD74 monoclonal antibody) in relapsed or refractory multiple myeloma

CD74, expressed in multiple myeloma (MM), was evaluated as a target for immunotherapy with milatuzumab (a humanized anti‐CD74 antibody). In a multicentre dose escalation study, 25 patients with advanced MM received milatuzumab doses of 1·5 (N = 8), 4·0 (N = 9), 8·0 (N = 4) or 16·0 mg/kg (N = 4) administered twice weekly x 4. They had a median of 5 prior treatments (17 post ≥1 stem cell transplantation) and were refractory (N = 7) or relapsed (N = 18) with generally short‐lived responses to last treatment (median 4·0 months). After increasing prophylactic medications and slowing administration, infusions were well tolerated (National Cancer Institute‐Common Terminology Criteria v3 toxicity Grades 1–2) with no dose‐limiting toxicity at higher doses. Only one patient developed borderline positive human anti‐milatuzumab antibody titres of uncertain clinical significance. Although milatuzumab was rapidly cleared from circulation with little serum accumulation and low trough levels, B‐cell levels were moderately decreased with treatment (median decrease, 34%). There were no objective responses by European Group for Blood and Marrow Transplantation criteria, but 5 of 19 patients (26%) who completed treatment in this heavily pretreated and generally refractory group had stable disease for ≥3 months post‐treatment (one continuing for 17 months). Disease stabilization and evidence of pharmacodynamic activity support further development for use in combination with other agents or as a drug conjugate. (Clinicaltrials.gov identifier: NCT00421525)
Water Transport Properties of Roots and Root Cortical Cells in Proton- and Al-Stressed Maize Varieties

Root and root cell pressure-probe techniques were used to investigate the possible relationship between Al- or H+-induced alterations of the hydraulic conductivity of root cells (LPc) and whole-root water conductivity (LPr) in maize (Zea mays L.) plants. To distinguish between H+ and Al effects two varieties that differ in H+ and Al tolerance were assayed. Based on root elongation rates after 24 h in nutrient solution of pH 6.0, pH 4.5, or pH 4.5 plus 50 [mu]M Al, the variety Adour 250 was found to be H+-sensitive and Al-tolerant, whereas the variety BR 201 F was found to be H+-tolerant but Al-sensitive. No Al-induced decrease of root pressure and root cell turgor was observed in Al-sensitive BR 201 F, indicating that Al toxicity did not cause a general breakdown of membrane integrity and that ion pumping to the stele was maintained. Al reduced LPc more than LPr in Al-sensitive BR 201 F. Proton toxicity in Adour 250 affected LPr more than LPc. In this Al-tolerant variety LPc was increased by Al. Nevertheless, this positive effect on LPc did not render higher LPr values. In conclusion, there were no direct relationships between Al- or H+-induced decreases of LPr and the effects on LPc. To our knowledge, this is the first time that the influence of H+ and Al on root and root cell water relations has been directly measured by pressure-probe techniques.
A Convenient Oxidation of Natural Glycosphingolipids to Their “Ceramide Acids” for Neoglycoconjugation

A new method to cleave the double bond of sphingolipids has been developed. Using limited concentrations of KMnO4 and an excess of NaIO4, in a neutral aqueous tert-butanol solvent system gave nearly quantitative yields of the oxidized product. A variety of natural glycosphingolipids (GSLs): GlcC, GalC, SGC, LC, Gb3C, Gb4C, Gg4C, Gb5C, and GM1C, gave the corresponding acids: 2-hydroxy-3-(N-acyl)-4-(O-glycosyl)-oxybutyric acids, i.e. “glycosyl ceramide acids” (GSL·CCOOH) in excellent yields (80–90%). Deacyl GSLs (dGSLs) were oxidized to acids containing the oligosaccharides devoid of hydrocarbon chains, i.e. “ceramide oligosaccharides” (dGSL·NRR1 CCOOH, where R = R1 = H; R = H, R1 = CH3CO; or R = R1 = Me). The efficacy of this method was demonstrated by transforming natural GSLs: GlcC, GalC, GalS, SGC, LC, Gb3C, and Gb4C into neoglycoproteins via coupling glycosyl ceramide acids (except GalS, which was coupled directly) to bovine serum albumin (BSA). Mass spectroscopic analysis of GalC-BSA conjugates, (GalC·CONH) n BSA and (GalS·NHCO) n BSA gave a value of 9 ± 1 and 16 ± 2 for n. Neoglycoconjugates derived from GlcC, GalC (type I and II and the behenic analog), SGC, LC, and Gb3C were recognized by the recombinant human immunodeficiency virus coat protein gp120 (rgp120). The GalS conjugate showed significantly reduced binding, and the Gb4C conjugate showed no binding. Thus, rgp120/GSL-BSA interaction requires a terminal galactose and/or glucose residue. TerminalN-acetylgalactosamine containing GSLs are not bound. The ceramide acid conjugates provide a more effective scaffold for presentation of glycone for rgp120 binding than those derived from dGSLs. The retention of receptor specificity of the glycoconjugates was validated by retention of the expected binding specificity of VT1 and VT2e for Gb3C and Gb4C conjugates, respectively. These studies open a new vista in the generation of glycoconjugates from GSLs and further emphasize the role of aglycone in glycolipid recognition.
Infectious scleritis: Clinical spectrum and management outcomes in India

In this retrospective case series, we studied the predisposing factors, causative organisms, clinical spectrum, and outcomes of 12 cases of culture-proven infectious scleritis. Nine of 12 patients had a history of preceding trauma (surgical or accidental). Past surgical history included small-incision cataract surgery (4), pterygium surgery (1), and trabeculectomy (1). Six patients had multifocal scleral abscesses due to Pseudomonas, Klebsiella, or Nocardia. Only 2 patients retained useful vision (>6/18). A poor visual acuity at presentation usually resulted in a worse visual outcome (P = 0.005). Four eyes developed phthisis. The addition of surgical intervention did not result in a significantly better visual outcome than medical management alone (P = 0.209), but resulted in a higher globe preservation rate (P = 0.045). Therefore, we concluded that infection must be ruled out in cases of scleritis with preceding history of trauma, and aggressive surgical intervention improves the anatomical outcome but does not change the visual outcome.
Abnormalities in brain systems supporting individuation and enumeration in autism

Previous work indicates that adults with autism display a decreased capacity when rapidly enumerating small sets of elements (i.e., subitizing), compared to typically developing (TD) individuals. This ability is crucial for fundamental visual functions such as object individuation and parallel processing. Thus, the deficit in autism suggests limits in these skills. To examine the neural basis of this limitation, adults with and without high functioning autism rapidly enumerated 1 to 8 randomly located squares during a neuroimaging study. Typically, adults are thought to use parallel visual processes to quantify up to three or four elements, and serial processes to enumerate more (5+) elements. We hypothesized that parietal lobe regions associated with counting would be recruited with smaller sets of elements in adults with autism, compared to TD adults. Consistent with this hypothesis, activation in parietal regions increased with smaller set sizes in adults with autism compared to TD adults. Increased activation for three elements was evident in several regions, including those thought to underlie subitizing. In addition, regions specific to the counting range in TD adults were often equally active for set sizes in the subitizing range in the adults with autism. Finally, significant deactivation was evident in TD adults, presumably reflecting relative suppression of regions specialized for competing processes, but was not apparent in adults with autism. These differences in brain function in adults with autism on a simple enumeration task suggest atypical brain organization and function that is likely to impact most visual tasks, especially those with multiple elements. Autism Res 2015. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function

Learning and memory depend on the activity-dependent structural plasticity of synapses and changes in neuronal gene expression. We show that deletion of the MEF2C transcription factor in the CNS of mice impairs hippocampal-dependent learning and memory. Unexpectedly, these behavioral changes were accompanied by a marked increase in the number of excitatory synapses and potentiation of basal and evoked synaptic transmission. Conversely, neuronal expression of a superactivating form of MEF2C results in a reduction of excitatory postsynaptic sites without affecting learning and memory performance. We conclude that MEF2C limits excessive synapse formation during activity-dependent refinement of synaptic connectivity and thus facilitates hippocampal-dependent learning and memory.
Breastfeeding initiation and duration: a 1990-2000 literature review.

OBJECTIVE To review the literature on breastfeeding initiation and duration and to delineate effective strategies for promoting positive breastfeeding behaviors. DATA SOURCES Computerized searches on MEDLINE, CINAHL, and the Cochrane Library. STUDY SELECTION Articles from indexed journals relevant to the objective and published after 1990 (except for classic findings) were reviewed. Although a myriad of pertinent articles was located, referenced citations were limited to three per point. When article selection was required for a specific point, preferences were given to (a) randomized controlled trials; (b) meta-analyses; (c) studies with the largest, most representative samples; and (d) investigations conducted in North America. DATA EXTRACTION Data were extracted and organized under the following headings: benefits of breastfeeding, breastfeeding initiation and duration, personal characteristics, attitudinal and intrapersonal characteristics, hospital policies and intrapartum experience, sources of support, breastfeeding interventions, and review implications. DATA SYNTHESIS Although the health benefits of breastfeeding are well documented and initiation rates have increased over the past 20 years, most mothers wean before the recommended 6-months postpartum because of perceived difficulties with breastfeeding rather than due to maternal choice. Women least likely to breastfeed are those who are young, have a low income, belong to an ethnic minority, are unsupported, are employed full-time, decided to breastfeed during or late in pregnancy, have negative attitudes toward breastfeeding, and have low confidence in their ability to breastfeed. Support from the mother's partner or a nonprofessional greatly increases the likelihood of positive breastfeeding behaviors. Health care professionals can be a negative source of support if their lack of knowledge results in inaccurate or inconsistent advice. Furthermore, a number of hospital routines are potentially detrimental to breastfeeding. Although professional interventions that enhance the usual care mothers receive increase breastfeeding duration to 2 months, these supportive strategies have limited long-term effects. Peer support interventions also promote positive breastfeeding behaviors and should be considered. CONCLUSIONS A promising intervention is the complementation of professional services with peer support from a mother experienced in breastfeeding. This lay support appears to be an effective intervention with socially disadvantaged women.
Absentee Bidders and the Declining Price Anomaly in Wine Auctions

The anomaly is concerned with the observation that in multiple item auctions of identical objects, prices tend to decline over time. I show that in the case of wine auctions, which have been analyzed frequently, the anomaly is likely to be caused by the fact that most bids are entered by absentees, who use nonoptimal bidding strategies. Therefore, wine auctions can hardly be used to illustrate the standard multiple‐object auction model.
Efficacy and Safety of Artemether-Lumefantrine in the Treatment of Acute, Uncomplicated Plasmodium falciparum Malaria: A Pooled Analysis

Randomized trials have confirmed the efficacy and safety of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria. Data from seven studies supported by Novartis (1996–2007), including 647 adults (> 16 years of age, 83.3% completed the study) and 1,332 children (≤ 16 years of age, 89.3% completed the study) with microscopically confirmed uncomplicated P. falciparum malaria and treated with the recommended regimen of AL, were pooled. The 28-day polymerase chain reaction–corrected parasitologic cure rate (primary efficacy endpoint) was 97.1% (495 of 510) in adults and 97.3% (792 of 814) in children (evaluable population). Gametocytemia prevalence after day was 4.2% (23 of 554) in adults and 0.9% (8 of 846) in children. No noteworthy safety signals were observed. Serious adverse events occurred in 1.4% of the adults and 1.3% of the children. This study is the largest data set to date assessing AL therapy for treatment of acute uncomplicated P. falciparum malaria. Artemether-lumefantrine showed high cure rates and rapid resolution of parasitemia, fever, and gametocytemia in adults and children, and showed an excellent safety and tolerability profile.
Prevention of selenite-induced cataractogenesis by hydroalchoholic extract of Echium amoenum: An experimental evaluation of the Iranian traditional eye medication

Introduction Cataract is a major health problem and characterized by cloudiness or opacification of the lens of the human eye (1,2). It is the leading cause of blindness and contributes to physiologically 50% of blindness (3). Age related cataract, affecting over 20 million of the nearly 45 million blind people worldwide with the highest incidence occurring in developing countries (1,4,5). Cataractogenesis is a multi-factorial disease associated with several risk factors such as ageing, diabetes, malnutrition, diarrhea, sunlight, smoking, hypertension, and renal failure (6,7). Free radical-induced oxidative stress is an important risk factor in the development of age-related Abstract Echium amoenum is an Iranian indigenous medicinal plant. In this research the effect of hydroalchoholic extract of this plant on sodium-selenite induced cataract formation was evaluated. Fifty five white rat pups were selected and divided into six groups. In first group (control 1) no elements injected. Second group (control 2) was received normal saline on 11-18 postpartum. Hydroalchoholic extract of Echium amoenum flower (400 mg/kg/day) intraperitonealy was injected into third group. Rats in group 4 th received sodium selenite (30 nmol/kg) on day 13 postpartum. In group 5 th , the extract was injected 2 days before selenite injection (once a day for two days). And in last group one day before selenite injection, the rats received a single dose of the extract. Cataract development was measured by slit-lamp. Lens opacification was analyzed in each group on day 7 after selenite administration. All lens in control and 3 th groups were clear. However, it was found different type of cataract grades formation in selenite group (2.2 ± 0.83). Cataract grades were 0.4 ± 0.5 and 0.6 ± 0.5 in groups 5 th and 6 th respectively. Echium amoenum extract significantly was shown a protective effect on selenite-induced cataract in rat. This effect is probably associated with antioxidant activity of this medicinal plant.
TurboFold II: RNA structural alignment and secondary structure prediction informed by multiple homologs

Abstract This paper presents TurboFold II, an extension of the TurboFold algorithm for predicting secondary structures for multiple RNA homologs. TurboFold II augments the structure prediction capabilities of TurboFold by additionally providing multiple sequence alignments. Probabilities for alignment of nucleotide positions between all pairs of input sequences are iteratively estimated in TurboFold II by incorporating information from both the sequence identity and secondary structures. A multiple sequence alignment is obtained from these probabilities by using a probabilistic consistency transformation and a hierarchically computed guide tree. To assess TurboFold II, its sequence alignment and structure predictions were compared with leading tools, including methods that focus on alignment alone and methods that provide both alignment and structure prediction. TurboFold II has comparable alignment accuracy with MAFFT and higher accuracy than other tools. TurboFold II also has comparable structure prediction accuracy as the original TurboFold algorithm, which is one of the most accurate methods. TurboFold II is part of the RNAstructure software package, which is freely available for download at http://rna.urmc. rochester.edu under a GPL license.
Potato Carboxypeptidase Inhibitor, a T-knot Protein, Is an Epidermal Growth Factor Antagonist That Inhibits Tumor Cell Growth*

Epidermal growth factor (EGF) and its receptor (EGFR) are involved in many aspects of the development of carcinomas, including tumor cell growth, vascularization, invasiveness, and metastasis. Because EGFR has been found to be overexpressed in many tumors of epithelial origin, it is a potential target for antitumor therapy. Here we report that potato carboxypeptidase inhibitor (PCI), a 39-amino acid protease inhibitor with three disulfide bridges, is an antagonist of human EGF. It competed with EGF for binding to EGFR and inhibited EGFR activation and cell proliferation induced by this growth factor. PCI suppressed the growth of several human pancreatic adenocarcinoma cell lines, both in vitro and in nude mice. PCI has a special disulfide scaffold called a T-knot that is also present in several growth factors including EGF and transforming growth factor α. PCI shows structural similarities with these factors, a fact that can explain the antagonistic effect of the former. This is the first reported example of an antagonistic analogue of human EGF.
Murine thymomas induced by fractionated-X-irradiation have specific T-cell receptor rearrangements and characteristics associated with day-15 to -16 fetal thymocytes

We report here that specific T-cell receptor rearrangements were observed in fractionated-X-irradiation-induced murine leukemias. Consistent gamma-chain rearrangements, limited beta-chain rearrangements, and no detectable alpha-chain rearrangements were observed. Gene expression studies revealed that, in comparison with normal thymus tissue, expression of alpha T-cell receptor genes was lower in the thymomas, beta expression was much higher but approximately equal to that of normal thymocytes, and gamma expression was significantly increased. After coupling these data with those from analyses using reagents against other surface markers, such as Lyt-2, L3T4, H-2, IL-2R and MEL-14, we concluded that the target T cells for fractionated-X-irradiation-induced transformation resemble fetal thymocytes from days 15 and 16 of gestation.
The contribution of GABA-mediated inhibitory mechanisms to visual response properties of neurons in the kitten's striate cortex

The effect of the microiontophoretic administration of the GABA antagonist bicuculline methiodide (BMI) on the responses of striate cortical neurons to light stimulation was investigated in kittens ranging in age between 11 and 28 d. The orientation sensitivity of the majority of the 88 neurons tested for this parameter decreased (40%) or was eliminated (18%) following the administration of BMI. Changes were seen in all layers and in all neuronal types, and the proportions of neurons that changed their orientation specificity were about the same during the second, third, and fourth postnatal weeks. Twenty-eight percent of the neurons were not affected in their orientation sensitivity by BMI. These neurons were recorded at all postnatal ages; they were located preferentially in layers IV and VI; and they had unimodal, bimodal, or ON-OFF mixed receptive fields. The remaining 14% of the neurons were initially unresponsive or responded in an erratic way to visual stimulation. These neurons became responsive and even exhibited orientation-specific responses during administration of BMI. The majority (56%) of direction-specific neurons became direction- nonspecific after the administration of BMI. Seventeen percent preserved some direction specificity, whereas 27% did not show any change at all. The effects of BMI on direction sensitivity were seen at all postnatal ages and on all neuronal types throughout layers III-VI. The majority of neurons unaffected by BMI in their direction sensitivity resided in layer VI. In those cases where orientation sensitivity was reduced, direction sensitivity (if present) was usually diminished as well. However, some neurons were found in which only 1 of the 2 parameters was significantly changed by BMI. The spatial structure of the receptive field, as revealed by stationary stimulation, was changed significantly by BMI in about half the neurons tested. A straightforward correlation between the alteration of orientation and/or direction sensitivity and changes in receptive-field structure was not found. The results demonstrate that, in the immature striate cortex, receptive-field properties of many neurons are determined by inhibitory processes mediated by GABA, which may also dictate the actual visual responsiveness of the neurons. The dissociations in the effects of BMI on orientation sensitivity, direction sensitivity, and receptive-field substructure indicate that the synaptic organization responsible for the various functional parameters is unlikely to be the same.
The sensitivity of a PDA‐based psychomotor vigilance task to sleep restriction in 10‐year‐old girls

The impact of sleep restriction on sustained attention in children has not been well quantified. To address this shortcoming, this study tested the sensitivity of a 5‐min personal digital assistant‐psychomotor vigilance task (PDA‐PVT) to sleep restriction in 14 female children [mean (SD) age = 10.6 ± 0.3 years]. The children underwent PDA‐PVT trials at regular intervals both before and after a sleep restriction (5 h time‐in‐bed) and a control (10 h time‐in‐bed) condition. Sleep restriction was associated with longer mean response times and increased number of lapses. These results are consistent with findings in the adult literature suggesting an association between inadequate sleep and impaired functioning. In conclusion, the 5‐min PDA‐PVT is sensitive to sleep restriction in pre‐adolescent female children supporting the utility of the PDA‐PVT for examining the impact of sleep deprivation on daytime functioning in children.