Miracle-dz/UniFAR-FTUs huggingface dataset:
Crossbridge and non‐crossbridge contributions to tension in lengthening rat muscle: force‐induced reversal of the power stroke

Lengthening of active muscle is an essential feature of animal locomotion, but the molecular processes occurring are incompletely understood. We therefore examined and modelled tension responses to ramp stretches (5% fibre length, L0) over a wide range of velocities (0.1–10 L0 s−1) of tetanized intact rat muscle fibre bundles (L0∼2 mm) with a resting sarcomere length of 2.5 μm at 20°C. Tension rose to a peak during stretch and decayed afterwards to a level which was higher than the prestretch tetanic tension. This residual force enhancement was insensitive to velocity. The tension rise during stretch showed an early transition (often appearing as an inflection) at ∼1 ms. Both the stretch (L1) and the tension rise at this transition increased in proportion to velocity. A second transition, marked by a reduction in slope, occurred at a stretch of ∼18 nm per half‐sarcomere; the rise in tension at this transition increased with velocity towards a plateau. Based on analyses of the velocity dependence of the tension and modelling, we propose that the initial steep increase in tension arises from increasing strain of all attached crossbridges and that the first transition reflects the tension loss due to the original post‐stroke heads executing a reverse power stroke. Modelling indicates that the reduction in slope at the second transition occurs when the last of the heads that were attached at the start of the ramp become detached. Thereafter, the crossbridge cycle is largely truncated, with prepower stroke crossbridges rapidly detaching at high strain and attaching at low strain, the tension being borne mainly by the prestroke heads. Analysis of the tension decay after the ramp and the velocity dependence of the peak tension suggest that a non‐crossbridge component increasingly develops tension throughout the stretch; this decays only slowly, reaching at 500 ms after the ramp ∼20% of its peak value. This is supported by the finding that, in the presence of 10 μmN‐benzyl‐p‐toluene sulphonamide (a myosin inhibitor), while isometric tension is reduced to ∼15%, and the crossbridge contribution to stretch‐induced tension rise is reduced to 30–40%, the peak non‐crossbridge contribution and the residual force enhancement remain high. We propose that the residual force enhancement is due to changes upon activation in parallel elastic elements, specifically that titin stiffens and C‐protein–actin interactions may be recruited.
What is the impact of genome-wide supported risk variants for schizophrenia and bipolar disorder on brain structure and function? A systematic review

The powerful genome-wide association studies (GWAS) revealed common mutations that increase susceptibility for schizophrenia (SZ) and bipolar disorder (BD), but the vast majority were not known to be functional or associated with these illnesses. To help fill this gap, their impact on human brain structure and function has been examined. We systematically discuss this output to facilitate its timely integration in the psychosis research field; and encourage reflection for future research. Irrespective of imaging modality, studies addressing the effect of SZ/BD GWAS risk genes (ANK3, CACNA1C, MHC, TCF4, NRGN, DGKH, PBRM1, NCAN and ZNF804A) were included. Most GWAS risk variations were reported to affect neuroimaging phenotypes implicated in SZ/BD: white-matter integrity (ANK3 and ZNF804A), volume (CACNA1C and ZNF804A) and density (ZNF804A); grey-matter (CACNA1C, NRGN, TCF4 and ZNF804A) and ventricular (TCF4) volume; cortical folding (NCAN) and thickness (ZNF804A); regional activation during executive tasks (ANK3, CACNA1C, DGKH, NRGN and ZNF804A) and functional connectivity during executive tasks (CACNA1C and ZNF804A), facial affect recognition (CACNA1C and ZNF804A) and theory-of-mind (ZNF804A); but inconsistencies and non-replications also exist. Further efforts such as standardizing reporting and exploring complementary designs, are warranted to test the reproducibility of these early findings.
Surgical complications in parenteral Subutex abusers.

INTRODUCTION There were anecdotal reports of an increase in the admissions of parenteral Subutex abusers to our hospital over the past five months. This case study aimed to analyse the surgical complications related to parenteral Subutex abuse and describe the demographics of this group of patients. METHODS We reviewed all admissions to our hospital between July and November 2005. Only parenteral Subutex abusers were included in this case study. RESULTS A total of 53 parenteral Subutex abusers were admitted during this period. 31 had surgical complications, while 22 presented with medical ones. Of the surgical patients, 12 had cellulitis and thrombophlebitis, six developed abscesses of the limbs, ten were patients with ischaemia and gangrene of the digits and limbs, one had septic arthritis, one had necrotising fasciitis, and one had a pseudoaneurysm of the femoral artery. There were no reported mortalities. Only nine patients needed surgical interventions. Most of the patients are young with a mean age of 34.2 years. There was a male predominance of 92.4 percent (49 out of 53). Malays are more frequently affected (72 percent, n=38), followed by Indians (15 percent, n=8), and Chinese (13 percent, n=7). CONCLUSION Parenteral Subutex abuse is a rising concern in Singapore. Many patients present to the surgical and orthopaedic departments for limb and vascular complications. Surgery has a limited role in their management, and most are treated conservatively and expectantly. The solution to this emerging trend requires inter-hospital and ministerial collaboration.
Simultaneous measurements of intracellular cAMP and L‐type Ca2+ current in single frog ventricular myocytes

1 The cAMP fluorescent probe FlCRhR was used to monitor changes in intracellular cAMP concentration ([cAMP]i) in isolated frog ventricular myocytes. The probe was introduced into the cell through a patch pipette which allowed simultaneous recording of the whole‐cell L‐type Ca2+ current (ICa). Ratiometric imaging was used to monitor [cAMP]i changes in response to the β‐adrenergic agonist isoprenaline (ISO) or to the direct adenylyl cyclase activator forskolin (FSK). 2 FlCRhR fluorescence was distributed in the cytosol in a striated pattern, with high fluorescence in the I‐bands and low fluorescence in the A‐bands. This pattern of distribution was mimicked by fluorescein dextran, another high molecular weight fluorescent molecule, and was therefore likely to be due to anisotropic diffusion of the probe in the cytosol due to the hindrance generated by sarcomeric proteins in the A‐bands. 3 Introduction of FlCRhR into the cell induced a small ≈70% stimulatory effect on basal ICa, attenuating about 2‐fold a subsequent response of ICa to 1‐10 μm ISO (from 400 to 200%). 4 Brief (10 s) application of a saturating concentration of ISO (1‐20 μm) to the cell induced a transient increase in both ICa and [cAMP]i. However, the [cAMP]i transient was ≈2‐fold shorter in duration than the ICa transient, i.e. ICa was still strongly enhanced when [cAMP]i had already returned to control level. This indicates that hydrolysis of cAMP by phosphodiesterases is not a rate limiting step in the recovery of ICa from ISO stimulation. 5 When the application of ISO was maintained, ICa and [cAMP]i responses followed a similar time course, with a half‐maximal response at ≈60 s. This suggests that activation of Ca2+ channels by cAMP‐dependent protein kinase occurs on a much faster time scale than the rise in [cAMP]i. 6 When the cells were exposed to FSK (13 μm), both responses of ICa and [cAMP]i were ≈2‐fold slower than with ISO. This demonstrates that the slower response of ICa to FSK is due to a slower rise in [cAMP]i rather than to some inhibitory effect of FSK on ICa or to a direct or priming effect of the stimulatory G protein Gs on Ca2+ channels. 7 Simultaneous measurements of [cAMP]i and ICa changes in intact cardiac myocytes opens the way to dissect the temporal sequence of events in the cAMP cascade mediating the response of the heart to a large number of hormones and inotropic agents.
Perceptions of Women’s Driving in Saudi Arabia: Relationship with Openness to Experience and Happiness

In September 2017, King Salman issued a decree that granted women the right to drive. Until then, Saudi Arabia was the only country in the world that did not allow women such a right. The Crown Prince Mohammed bin Salman's Vision 2030 plans to modernize the country was a leading force towards this change, but measures to make Saudi Arabia a moderate Islamic country and reduce its dependency on oil revenues have garnered mixed reactions. This has created a need to understand the public’s opinion on women’s driving; but, no tools to measure such perceptions existed. Thus, the aim of the study was to examine the perceptions of women’s driving in Saudi Arabia by creating the ‘Women Driving Perception Scale’ (WDPS). The investigation also focuses on the relationship between such perceptions and levels of openness and happiness. With a reliability of 0.90, the WDPS showed that women are more enthusiastic about their driving than men. Further, there is a positive correlation between the WDPS, openness to experience and subjective happiness, although males score higher on happiness altogether. Factors such as marital and professional status, and women’s reasons for driving were also examined. The WDPS was useful in providing insight on the public’s perceptions and thoughts on women’s driving.
Social phobia, avoidant personality disorder and atypical depression: co-occurrence and clinical implications

Background. Increasing attention has been directed in recent years to the detection and treatment of psychiatric co-morbidity among depressed individuals. The overlap of social phobia (SP) and avoidant personality disorder (APD) has been well recognized and a relationship between these disorders and depression has been suggested. Methods. The pattern and clinical implications of co-morbidity of SP and APD with major depressive disorder (MDD), diagnosed by DSM-III-R criteria, were studied among 243 out-patients presenting with depression. Results. Overall, 26·7% of adults in our sample with MDD met criteria for SP and 28·4% for APD. Almost two-thirds of depressed adults meeting criteria for social phobia or avoidant personality disorder met criteria for both (SP+APD). Depressed adults who met criteria for both SP+APD exhibited a significantly higher proportion of atypical depression (54·8%) compared with those with neither SP nor APD (31·1%). Among depressed patients, the co-occurrence of SP with APD was also associated with an earlier age of onset of MDD, a greater number of co-morbid Axis I diagnoses, and greater impairment of social adjustment and assertiveness. Conclusions. Results confirm the overlap of SP and APD in a depressed population and the high prevalence of these disorders in MDD. They suggest that depressed individuals with both SP and APD but not SP alone are at particularly high risk for atypical depression and for social dysfunction in excess of that caused by a current major depression.
Combined Paroxetine and Clonazepam Treatment Strategies Compared to Paroxetine Monotherapy for Panic Disorder

Despite the widespread application of combined selective serotonin reuptake inhibitors (SSRI) and benzodiazepine treatment for panic disorder, there has been relatively little systematic assessment of the safety and efficacy of this therapeutic strategy. Although the limited number of studies to date suggest a more rapid onset of benefit with combined treatment, this study is the first to address the critical question of whether continued combined treatment confers superior efficacy. This study is a randomized, double-blind, three-arm study in patients with panic disorder (n = 60), comparing the efficacy and safety of paroxetine and placebo (PP), paroxetine coadministered with clonazepam followed by a tapered benzodiazepine discontinuation phase (PC-D), and ongoing combination treatment (PC-M). All treatment groups demonstrated significant improvement by endpoint. There was a significant advantage for the combined treatment groups early in treatment but, subsequently, outcome in all three groups was similar. A trend towards greater achievement of endpoint remission status for the PC-D group was attenuated when variability in baseline severity was considered. The results of this study should be interpreted in the context of a relatively moderate sample size and higher rates of early dropout. Combined treatment with paroxetine and clonazepam resulted in more rapid response than with the SSRI alone, but there was no differential benefit beyond the initial few weeks of therapy. Initiating combined treatment followed by benzodiazepine taper after a few weeks may provide early benefit while avoiding the potential adverse consequences of long-term combination therapy.
No Association between Akathisia or Parkinsonism and Suicidality in treatment-Resistant Schizophrenia

Akathisia and drug-induced Parkinsonism have traditionally beenassociated with depression and suicidality based on case study evidence. In this subanalysis, patients with treatment resistant schizophrenia were rated on the Comprehensive Psychopathological Rating Scale, Barnes Akathisia Scale and Simpson–Angus extrapyramidal side-effect scale at two time points (n = 86 at first assessment; n = 67 at secondassessment). At no time point was there any significant relationship between akathisia and depression/suicidality or distress associated with akathisia and Parkinsonism with suicidality. These preliminary findings warrant further investigation.
Recent controversies about MDR and XDR‐TB: Global implementation of the WHO shorter MDR‐TB regimen and bedaquiline for all with MDR‐TB?

Tuberculosis (TB) is now the biggest infectious disease killer worldwide. Although the estimated incidence of TB has marginally declined over several years, it is out of control in some regions including in Africa. The advent of multidrug‐resistant TB (MDR‐TB) and extensively drug‐resistant TB (XDR‐TB) threatens to further destabilize control in several regions of the world. Drug‐resistant TB constitutes a significant threat because it underpins almost 25% of global TB mortality, is associated with high morbidity, is a threat to healthcare workers and is unsustainably costly to treat. The advent of highly resistant TB with emerging bacillary resistance to newer drugs has raised further concern. Encouragingly, in addition to preventative strategies, several interventions have recently been introduced to curb the drug‐resistant TB epidemic, including newer molecular diagnostic tools, new (bedaquiline and delamanid) and repurposed (linezolid and clofazimine) drugs and shorter and individualized treatment regimens. However, there are several controversies that surround the use of new drugs and regimens, including whether, how and to what extent they should be used, and who specifically should be treated so that outcomes are optimally improved without amplifying the burden of drug resistance, and other potential drawbacks, thus sustaining effectiveness of the new drugs. The equipoise surrounding these controversies is discussed and some recommendations are provided.
Calcite microneedle arrays produced by inorganic ion-assisted anisotropic dissolution of bulk calcite crystal.

Besides studies on the mineralization process, research on the demineralization of minerals provides another way to understand the crystallization mechanism of biominerals and fabricate crystals with complicated morphologies. The formation of ordered arrays of c-axis-oriented calcite microneedles with a tri-symmetric structure and lengths of more than 20 μm was realized on a large scale for the first time through anisotropic dissolution of calcite substrates in undersaturated aqueous solution in the presence of ammonium salts. The lengths and the aspect ratios of the calcite microneedles can be tuned by simply changing the concentrations of the ammonium salts and the dissolution time. The shape of the transverse cross sections of the calcite microneedles obtained in the presence of NH4 Cl and NH4 Ac is almost regularly triangular. The tri-symmetric transverse cross-section geometry of the calcite microneedles could be attributed to the tri-symmetric feature of rhombohedral calcite atomic structures, the synergetic interactions between electrostatic interaction of ammonium ions and dangling surface carbonate groups, and the ion incorporation of halide ions.
Self-assessment via a blended-learning strategy to improve performance in an accounting subject

The General Accounting subject is on the curricula of five different bachelor’s degrees offered in the Faculty of Economics and Business at the University of Granada (UGR), Spain. In a coordinated way, all the lecturers involved in this subject have generated interactive materials and a methodology that allows students to undertake online self-assessment activities that are very similar to the final exam. Following a blended-learning methodology, General Accounting combines classroom education techniques with the use of information and communication technology (ICT) tools, and the students work to improve their grades. In the 2012/13 academic year, students on two of the degrees were consulted about their overall satisfaction with using this platform. From the results, we can highlight the positive appraisal of the interestingness and usefulness of activities on the platform. We also obtained a positive correlation between the students’ access to the activities and the grades obtained in them, and the final grades obtained in the subject. La asignatura Contabilidad general se imparte en cinco titulaciones de grado que se ofertan en la Facultad de Ciencias Económicas y Empresariales de la Universidad de Granada. Los profesores de la asignatura han generado, de forma coordinada, materiales educativos en línea asociados a una metodología que permite que los estudiantes realicen cada año actividades de autoevaluación similares a las que están disponibles en la asignatura en su evaluación para conseguir el título de grado. Siguiendo la metodología blended-learning, que combina técnicas de educación presenciales con el uso de herramientas TIC, los estudiantes trabajan en la materia y mejoran en sus resultados académicos. En el presente curso se ha consultado a estudiantes de dos de los grados sobre la satisfacción general en el uso de la plataforma. De los resultados obtenidos, podemos destacar la valoración positiva de los estudiantes respecto a la utilidad de las actividades planteadas a través de la plataforma, así como su interés; también cabe reseñar la correlación positiva hallada entre el acceso a la plataforma y las calificaciones en los ejercicios de autoevaluación, y la calificación final de la asignatura.
Azathioprine or 6-mercaptopurine for inducing remission of Crohn's disease.

OBJECTIVES To determine the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn's disease. SEARCH STRATEGY Studies were selected using the MEDLINE data base (1966 - December 1997), abstracts from major gastrointestinal meetings and references from published articles and reviews. The Cochrane Controlled Trials Register and the Inflammatory Bowel Disease Review Group Trials Register was also searched. SELECTION CRITERIA Eight randomized placebo controlled trials of azathioprine and 6-mercaptopurine therapy in adult patients were identified: five dealt with active disease and three had multiple therapeutic arms. DATA COLLECTION AND ANALYSIS Data were extracted by three independent observers based on the intention to treat principle. Each study was given a quality score based on predetermined criteria. Extracted data were converted to 2X2 tables (response versus no response and antimetabolite versus placebo) and then synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel ('Odds Ratio' in MetaView). MAIN RESULTS The odds ratio of a response to azathioprine or 6-mercaptopurine therapy compared with placebo in active Crohn's disease was 2.36 (95% CI 1.57-3.53). This corresponded to a number needed to treat of about 5 to observe an effect of therapy in one patient. When the two trials using 6-mercaptopurine in active disease were excluded from the analysis, the odds ratio of response was 2.04 (CI 1.24 - 3.35). Treatment >/= 17 weeks increased the odds ratio of a response to 2.51 (CI 1.63-3. 88). A steroid sparing effect was seen with an odds ratio of 3.86 (CI 2.14 - 6.96), corresponding to a number needed to treat of about 3 to observe steroid sparing in one patient. Adverse events requiring withdrawal from a trial, principally allergy, leukopenia, pancreatitis, and nausea were increased on therapy with an odds ratio of 3.01 (CI 1.30 - 6.96). The number needed to treat to observe one adverse event in one patient treated with azathioprine or 6-mercaptopurine was 14. REVIEWER'S CONCLUSIONS Azathioprine and 6-mercaptopurine are effective therapy for inducing remission in active Crohn's disease. The odds ratio of response increases after >/= 17 weeks of therapy, suggesting that there is a minimum length of time for a trial of azathioprine or 6-mercaptopurine therapy. Adverse events were more common among patients on therapy.
Alteration in Auxin Homeostasis and Signaling by Overexpression Of PINOID Kinase Causes Leaf Growth Defects in Arabidopsis thaliana

In plants many developmental processes are regulated by auxin and its directional transport. PINOID (PID) kinase helps to regulate this transport by influencing polar recruitment of PIN efflux proteins on the cellular membranes. We investigated how altered auxin levels affect leaf growth in Arabidopsis thaliana. Arabidopsis mutants and transgenic plants with altered PID expression levels were used to study the effect on auxin distribution and leaf development. Single knockouts showed small pleiotropic growth defects. Contrastingly, several leaf phenotypes related to changes in auxin concentrations and transcriptional activity were observed in PID overexpression (PIDOE) lines. Unlike in the knockout lines, the leaves of PIDOE lines showed an elevation in total indole-3-acetic acid (IAA). Accordingly, enhanced DR5-visualized auxin responses were detected, especially along the leaf margins. Kinematic analysis revealed that ectopic expression of PID negatively affects cell proliferation and expansion rates, yielding reduced cell numbers and small-sized cells in the PIDOE leaves. We used PIDOE lines as a tool to study auxin dose effects on leaf development and demonstrate that auxin, above a certain threshold, has a negative affect on leaf growth. RNA sequencing further showed how subtle PIDOE-related changes in auxin levels lead to transcriptional reprogramming of cellular processes.