Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of post-finasteride patients showing persistent sexual side effects and anxious/depressive symptomatology.

INTRODUCTION Observations performed in a subset of subjects treated with finasteride (an inhibitor of the enzyme 5α-reductase) for male pattern hair loss seem to indicate that sexual dysfunction as well as anxious/depressive symptomatology may occur at the end of the treatment and continue after discontinuation. AIM A possible hypothesis to explain depression symptoms after finasteride treatment might be impairment in the levels of neuroactive steroids. Therefore, neuroactive steroid levels were evaluated in paired plasma and cerebrospinal fluid samples obtained from male patients who received finasteride for the treatment of androgenic alopecia and who, after drug discontinuation, still show long-term sexual side effects as well as anxious/depressive symptomatology. METHODS The levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in three postfinasteride patients and compared to those of five healthy controls. MAIN OUTCOME MEASURES Neuroactive steroid levels in plasma and cerebrospinal fluid of postfinasteride patients and healthy controls. RESULTS At the examination, the three postfinasteride patients reported muscular stiffness, cramps, tremors, and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Severity and frequency of the anxious/depressive symptoms were quite variable; overall, all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in patients showed some interindividual differences. However, the most important finding was the comparison of their neuroactive steroid levels with those of healthy controls. Indeed, decreased levels of tetrahydroprogesterone, isopregnanolone and dihydrotestosterone and increased levels of testosterone and 17β-estradiol were reported in cerebrospinal fluid of postfinasteride patients. Moreover, decreased levels of dihydroprogesterone and increased levels of 5α-androstane-3α,17β-diol and 17β-estradiol were observed in plasma. CONCLUSION The present observations confirm that an impairment of neuroactive steroid levels, associated with depression symptoms, is still present in androgenic alopecia patients treated with finasteride despite the discontinuation of the treatment.
Microtensile Bond Strength of a Resin Cement to Silica‐Based and Y‐TZP Ceramics Using Different Surface Treatments

PURPOSE To evaluate the effects of different surface treatments on the microtensile bond strength (μTBS) of bonding between resin cement and lithia or zirconia-based ceramics using an in vitro study. MATERIALS AND METHODS Three zirconia ceramic blocks (IPS e.max ZirCAD) and three lithium disilicate ceramic blocks (IPS e.max CAD) were sintered and duplicated in resin composite. The zirconia specimens underwent various treatments (n = 1): (i) Sandblast + primer (ZiSa); (ii) sandblast + laser irradiation + primer (ZiSaLa); or (iii) laser irradiation + primer (ZiLa). The lithium disilicate specimens also underwent various treatments: (i) sandblast + HF + silane (LiSaE); (ii) sandblast + silane (LiSa); or (iii) sandblast + laser irradiation + silane (LiSaLa). The ceramic-composite blocks were cemented with resin cement and cut to produce bars with approx. 1 mm2 bonding areas. The specimens were thermocycled, and bond strength tests were performed in a universal testing machine. The fracture type was determined by observing the fractured surface under a stereomicroscope. The mean bond strengths of the specimens were statistically analyzed using one-way ANOVA and Duncan's tests (α = 0.05). RESULTS Mean comparison of the μTBS showed no significant difference between LiSaE and LiSa (p > 0.05), but significant differences between LiSaE and other groups (p ≤ 0.01). No significant differences were found between the ZiSaLa and ZiSa groups (p > 0.05). The modes of failure in all groups were mostly adhesive (57% to 80%). The mean bond strengths in laser-irradiated ceramics were significantly lower than those from other surface treatments. All ZiLa specimens debonded before testing (pretest failure). CONCLUSIONS Lithium disilicate ceramic surface treated with a combination of sandblasting and silane application provided a bond strength comparable to that provided by sandblasting in combination with acid etching and applying silane. Groups treated with laser irradiation had significantly lower bond strengths than other groups.
Effects of Acute Hypoglycemia on Motivation and Cognitive Interference in People with Type 1 Diabetes

Aims: To examine the effect of acute hypoglycemia on motivation and cognitive interference in adult humans with type 1 diabetes. Methods: A hyperinsulinemic glucose clamp was used to either maintain euglycemia (arterialized blood glucose 4.5 mmol/L) or induce hypoglycemia (2.6 mmol/L) in 16 adults with type 1 diabetes, each of whom were studied on 2 separate occasions in a counterbalanced order. During each study condition, the subjects completed parallel tests of cognitive function. The Dundee Stress State Questionnaire (DSSQ) was administered before and after the cognitive function tests. Results: Hypoglycemia decreased task-relevant (P = 0.03) and increased task-irrelevant (P = 0.02) interference. Self-focus of attention was much higher after hypoglycemia than euglycemia (P = 0.02). Motivation declined to a similar extent during the euglycemia and hypoglycemia conditions (P = 0.07). Hypoglycemia produced a negative mood state with a significant fall in energy levels (P = 0.03) and a concomitant rise in anxiety level (P = 0.05). The subjective perception of concentration was unaffected during hypoglycemia (P = 0.14), and the scores for control and confidence did not fall (P = 0.19). Conclusions: In people with type 1 diabetes, hypoglycemia causes a state of heightened self-awareness and distraction during active mental activity. This is likely to leave fewer processing resources available to allow completion of cognitive tasks. Acute hypoglycemia induces a state of significant worry and anxiety that is likely to affect the social, personal, and work activities of people with diabetes.
Taming hyperactive hDNase I: Stable inducible expression of a hyperactive salt‐ and actin‐resistant variant of human deoxyribonuclease I in CHO cells

While the most common causes of clonal instability are DNA copy number loss and silencing, toxicity of the expressed protein(s) may also induce clonal instability. Human DNase I (hDNase I) is used therapeutically for the treatment of cystic fibrosis (CF) and may have potential benefit for use in systemic lupus erythematosus (SLE). hDNase I is an endonuclease that catalyzes degradation of extracellular DNA and is inhibited by both salt and G‐actin. Engineered versions of hDNase I, bearing multiple point mutations, which renders them Hyperactive, Salt‐ and Actin‐Resistant (HSAR‐hDNase I) have been developed previously. However, constitutive expression of HSAR‐hDNase I enzymes has been very challenging and, despite considerable efforts and screening thousands of clones, no stable clone capable of constitutive expression had been obtained. Here, we developed a regulated expression system for stable expression of an HSAR‐hDNase I in Chinese Hamster Ovary (CHO) cells. The HSAR‐hDNase I clones were stable and, upon induction, expressed enzymatically functional protein. Our findings suggest that degradation of host's DNA mediated by HSAR‐hDNase I during cell division is the likely cause of clonal instability observed in cells constitutively expressing this protein. Purified HSAR‐hDNase I was both hyperactive and resistant to inhibition by salt and G‐actin, resulting in an enzyme having ca. 10‐fold greater specific activity and the potential to be a superior therapeutic agent to wild type (WT) hDNase I. Furthermore, the ability to regulate hDNase I expression has enabled process development improvements that achieve higher cell growth and product titers while maintaining product quality. © 2017 American Institute of Chemical Engineers Biotechnol. Prog. , 32:523–533, 2017
Identification of integrin receptors on cultured human bone cells

The interactions of bone cells with their surrounding extracellular microenvironment may be mediated by integrins, a family of heterodimeric glycoproteins consisting of α and β subunits that noncovalently interact to form cell‐substratum adhesion receptors. We previously described the integrins on calvarial bone cells in rats with use of polyclonal antibodies against some integrin subunits. In the present study, we expanded this initial characterization by employing a more complete panel of monoclonal antibodies to identify integrins on human bone cells. Minced fragments of trabecular bone obtained during total knee arthroplasty were grown in culture until bone cells became confluent. The cells then were dissociated, plated again, grown to confluence, and assayed for alkaline phosphatase activity, response of cyclic adenosine monophosphate to stimulation with parathyroid hormone, and osteocalcin content. The percentage of the cells that adhered to various substrates was measured; 60–70% adhered to type‐I collagen, fibronectin, vitronectin, and poly‐D‐lysine; 40–50% adhered to type‐IV collagen, laminin, and gelatin; and only 10% adhered to fibrinogen. Flow cytometric analysis with anti‐integrin monoclonal antibodies and sodium dodecyl sulfate‐polyacryamide gel electrophoresis analysis of immunoprecipitates of the human bone cells revealed high levels of α1β1, α3β1, α5β1, and αVβ5 integrins and much lower levels of α2β1, α4β1, αVβ1, and αVβ3 integrins. This description of the integrin repertoire of cultured human bone cells represents the first step toward an understanding of the role played by integrins in the growth, maintenance, and repair of bone.
The effect of body condition on metabolic changes associated with intake of food by the cow

1. Changes in concentrations of metabolites in blood and rumen fluid were measured in cows when fat and when thin and when given hay and concentrates at a restricted level or ad lib. 2. When fed ad lib. , cows consumed 24% more food when thin than when fat. 3. Concentrations in rumen fluid of acetate and propionate after feeding at both levels did not differ significantly between fat and thin cows. 4. Concentrations in blood of the lipogenic substrates acetate and 3-hydroxybutyrate did not differ between fat and thin cows after feeding, but glucose concentration fell more rapidly in thin cows especially when fed ad lib. Propionate rose more in thin cows than in fat cows when fed ad lib. Non-esterified fatty acids were higher in fat cows before feeding, but fell to similar levels to those in thin cows after feeding. 5. The results are interpreted as indicating a more rapid rate of fatty acid synthesis in adipose tissue of thin cows. This in turn tends to lower blood levels of fatty acid precursors and so enhance the rate of their absorption from the rumen. This in turn permits higher intake of food before short-term chemical regulators of intake start to operate.
Regulation of the Sequential Processing of Semliki Forest Virus Replicase Polyprotein*

The replication of most positive-strand RNA viruses and retroviruses is regulated by proteolytic processing. Alphavirus replicase proteins are synthesized as a polyprotein, called P1234, which is cleaved into nsP1, nsP2, nsP3, and nsP4 by the carboxyl-terminal protease domain of nsP2. The cleavage intermediate P123+nsP4 synthesizes minus-strand copies of the viral RNA genome, whereas the completely processed complex is required for plus-strand synthesis. To understand the mechanisms responsible for this sequential proteolysis, we analyzed in vitro translated Semliki Forest virus polyproteins containing noncleavable processing sites or various deletions. Processing of each of the three sites in vitro required a different type of activity. Site 3/4 was cleaved in trans by nsP2, its carboxyl-terminal fragment Pro39, and by all polyprotein proteases. Site 1/2 was cleaved in cis with a half-life of about 20–30 min. Site 2/3 was cleaved rapidly in trans but only after release of nsP1 from the polyprotein exposing an “activator” sequence present in the amino terminus of nsP2. Deletion of amino-terminal amino acids of nsP2 or addition of extra amino acid residues to its amino terminus specifically inhibited the protease activity that processes the 2/3 site. This sequence of delayed processing of P1234 would explain the accumulation of P123 plus nsP4, the early short-lived minus-strand replicase. The polyprotein stage would allow correct assembly and membrane association of the RNA-polymerase complex. Late in infection free nsP2 would cleave at site 2/3 yielding P12 and P34, the products of which, nsP1–4, are distributed to the plasma membrane, nucleus, cytoplasmic aggregates, and proteasomes, respectively.
E-shaped patch antennas for high-speed wireless networks

Thin, broad-band, E-shaped microstrip patch antennas (ESPAs), operating in the 5-6 GHz frequency range, are presented. They are intended for high-speed (IEEE 802.11a, 54 Mb/s) wireless computer local area networks (WLAN) and other wireless communication systems. They are suitable for WLAN adaptor cards in the PCMCIA (also known as PC) format, allowing users of current notebook computers to upgrade to this high-speed wireless standard at a low cost. Importantly, our antennas are thin enough to be accommodated in a PCMCIA card of standard 5-mm thickness, without making the antenna end thicker than the card itself. Two different closely spaced antenna pairs are also presented for diversity. A new ESPA configuration with a microstrip feed is presented for easy integration with microwave transceivers. In all cases, within the two IEEE 802.11a WLAN bands (5.15-5.35 GHz and 5.725-5.825 GHz), the reflection coefficient at the antenna input is <-10 dB and in both antenna pairs, mutual coupling between the two antennas is <-20 dB.
Nephrotoxicity—What Do We Know and What Don't We Know?

Nephrotoxicity is the development of functional or structural kidney damage after exposure to one or more of a wide variety of drugs, other treatments or exogenous toxins, and may lead to a variety of functional consequences and structural lesions. Nephrotoxicity is important as it may occur in a substantial proportion of children treated with certain drugs and occasionally lead to severe renal impairment that may prevent the delivery of optimal anticancer treatment and/or reduce the quality of life of long-term survivors. This article describes what is currently known about nephrotoxicity occurring in children treated for malignancy by summarizing published information about the clinical characteristics and long-term outcome of, and the risk factors for the development of, ifosfamide and platinum-induced renal toxicity. Published guidelines for the evaluation and surveillance of nephrotoxicity, and the still incomplete understanding of its pathogenesis, are also outlined. Many gaps in our knowledge of nephrotoxicity are highlighted, including the lack of detailed knowledge about its overall incidence and very long-term impact, the nephrotoxic potential of new drugs, the efficacy of surveillance protocols, the relevance of proteinuria as a component of nephrotoxicity, and our current inability to reliably predict or prevent many episodes of nephrotoxicity.
Symptomatic Relief is Related to Serum Free Triiodothyronine Concentrations during Follow-up in Levothyroxine-Treated Patients with Differentiated Thyroid Cancer.

AIM Patients on levothyroxine-treatment frequently have complaints although TSH is within the reference range. Moreover, FT3 is often low in these patients. The clinical significance of this disequilibrium is studied here. PATIENTS, METHODS We conducted a retrospective longitudinal study including 319 patients with differentiated thyroid carcinoma on LT4-medication (1.8 [1.6,2.1] µg/kg body weight). Patients were followed at 2309 visits for at median 63 [46,81] months. Association of reported complaints during follow-up with changes in thyroid parameters were analysed using a generalised linear mixed model accounting for within-variability and intra-subject correlations. RESULTS 26% of patients expressed hypothyroid and 9.7% hyperthyroid complaints at any one visit, rates per visit being 6.5% and 2%, respectively. During follow-up, median changes in spans were as follows, LT4-dose 0.49 [IQR 0.29,0.72] µg/kg, FT3 1.77 [1.25,2.32] pmol/l, FT4 9.80 [6.70,12.8] pmol/l and TSH 1.25 [0.42,2.36] mIU/l. While rates of both hypothyroid or hyperthyroid symptoms were significantly related to all three thyroid parameters, the relationship of hypothyroid symptoms with FT3 extended to a below reference TSH range. Hypothyroid symptom relief was associated with both a T4 dose giving TSH-suppression below the lower reference limit and FT3 elevated further into the upper half of its reference range. In multivariable analysis, relationships between complaints and FT3 concentrations remained significant after adjusting for gender, age and BMI. CONCLUSION Residual hypothyroid complaints in LT4-treated patients are specifically related to low FT3 concentrations. This supports an important role of FT3 for clinical decision making on dose adequacy, particularly in symptomatic athyreotic patients.
13q14 Deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia

Deletion at 13q14 is detected by fluorescence in situ hybridization (FISH) in about 50% of chronic lymphocytic leukemia (CLL). Although CLL with 13q deletion as the sole cytogenetic abnormality (del13q‐only) usually have good prognosis, more aggressive clinical courses are documented for del13q‐only CLL carrying higher percentages of 13q deleted nuclei. Moreover, deletion at 13q of different sizes have been described, whose prognostic significance is still unknown. In a multi‐institutional cohort of 342 del13q‐only cases and in a consecutive unselected cohort of 265 CLL, we investigated the prognostic significance of 13q deletion, using the 13q FISH probes locus‐specific identifier (LSI)‐D13S319 and LSI‐RB1 that detect the DLEU2/MIR15A/MIR16‐1 and RB1 loci, respectively. Results indicated that both percentage of deleted nuclei and presence of larger deletions involving the RB1 locus cooperated to refine the prognosis of del13q‐only cases. In particular, CLL carrying <70% of 13q deleted nuclei with deletions not comprising the RB1 locus were characterized by particularly long time‐to‐treatment. Conversely, CLL with 13q deletion in <70% of nuclei but involving the RB1 locus, or CLL carrying 13q deletion in ≥70% of nuclei, with or without RB1 deletions, collectively experienced shorter time‐to‐treatment. A revised flowchart for the prognostic FISH assessment of del13q‐only CLL, implying the usage of both 13q probes, is proposed. © 2011 Wiley‐Liss, Inc.
Quantitative time-course metabolomics in human red blood cells reveal the temperature dependence of human metabolic networks

The temperature dependence of biological processes has been studied at the levels of individual biochemical reactions and organism physiology (e.g. basal metabolic rates) but has not been examined at the metabolic network level. Here, we used a systems biology approach to characterize the temperature dependence of the human red blood cell (RBC) metabolic network between 4 and 37 °C through absolutely quantified exo- and endometabolomics data. We used an Arrhenius-type model (Q10) to describe how the rate of a biochemical process changes with every 10 °C change in temperature. Multivariate statistical analysis of the metabolomics data revealed that the same metabolic network-level trends previously reported for RBCs at 4 °C were conserved but accelerated with increasing temperature. We calculated a median Q10 coefficient of 2.89 ± 1.03, within the expected range of 2–3 for biological processes, for 48 individual metabolite concentrations. We then integrated these metabolomics measurements into a cell-scale metabolic model to study pathway usage, calculating a median Q10 coefficient of 2.73 ± 0.75 for 35 reaction fluxes. The relative fluxes through glycolysis and nucleotide metabolism pathways were consistent across the studied temperature range despite the non-uniform distributions of Q10 coefficients of individual metabolites and reaction fluxes. Together, these results indicate that the rate of change of network-level responses to temperature differences in RBC metabolism is consistent between 4 and 37 °C. More broadly, we provide a baseline characterization of a biochemical network given no transcriptional or translational regulation that can be used to explore the temperature dependence of metabolism.
Text-message-based drinking assessments and brief interventions for young adults discharged from the emergency department.

BACKGROUND Brief interventions have the potential to reduce heavy drinking in young adults who present to the emergency department (ED), but require time and resources rarely available. Text-messaging (TM) may provide an effective way to collect drinking data from young adults after ED discharge as well as to provide immediate feedback and ongoing support for behavior change. The feasibility of screening young adults in the ED, recruiting them for a TM-based interventional trial, collecting weekly drinking data through TM, and the variance in drinking outcomes remains unknown. METHODS Young adults in 3 urban EDs (n = 45; aged 18 to 24 years, 54% women) identified as hazardous drinkers by the Alcohol Use Disorders Identification Test-Consumption score were randomly assigned to weekly TM-based feedback with goal setting (Intervention), weekly TM-based drinking assessments without feedback (Assessment), or control. Participants in the Intervention group who reported ≥5 (for men) and ≥4 (for women) maximum drinks during any one 24-hour period were asked whether they would set a goal to reduce their drinking the following week. We describe the interaction with TM and goal setting. We also describe the heavy drinking days (HDDs), drinks per drinking day (DPDD) using timeline follow-back procedure at baseline and 3 months. RESULTS We screened 109 young adults over 157 hours across 24 unique days and 52 (48%; 95% CI 38 to 50) screened positive for hazardous drinking. Of these, 45 (87%; 95% CI 74 to 94) met inclusion criteria, were enrolled and randomized, and 6 (13%; 95% CI 5 to 27) did not complete 3-month web-based follow-up; 88% (95% CI 84 to 91) of weekly TM-based drinking assessments were answered, with 77% (95% CI 58 to 90) of participants responding to all 12 weeks. Agreeing to set a goal was associated with a repeat HDD 36% (95% CI 17 to 55) of the time compared with 63% (95% CI 44 to 81) when not willing to set a goal. At 3 months, participants that were exposed to the TM-based intervention had 3.4 (SD 5.4) fewer HDDs in the last month and 2.1 (SD 1.5) fewer DPDD when compared to baseline. CONCLUSIONS TM can be used to assess drinking in young adults and can deliver brief interventions to young adults discharged from the ED. TM-based interventions have the potential to reduce heavy drinking among young adults but larger studies are needed to establish efficacy.