Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of back pain, its effect on functional ability and health-related quality of life in lower limb amputees secondary to trauma or tumour: a comparison across three levels of amputation

Background and Objectives: The prevalence of back pain and its effect on function and health-related quality of life across three levels of lower limb amputation secondary to trauma or tumour was studied. Study design: Cross-sectional survey. Methods: Forty-six lower limb amputees, aged 19–78 years, participated. The Roland Morris disability questionnaire (RMDQ) and the short form 36 health survey (SF-36) were used. Results: Participants reported more back pain after amputation than before (p < 0.001). There was a significant association between back pain daily or several times/week and severe or moderate disability reporting on the RMDQ (p = 0.003). On the SF-36, the group as a whole scored significantly lower in health-related quality of life with regard to physical functioning, role physical, bodily pain, general health, social functioning and the physical component summary (PCS), and significantly higher in the mental component summary (MCS) compared to normative Swedish data. When all three levels of amputation were compared, no statistically significant differences were found in the RMDQ or SF-36 results. Conclusions: There was a high prevalence of back pain after amputation. Almost all participants having back pain daily or several times per week reported severe or moderate disability on the RMDQ. The group as a whole scored significantly lower for health-related quality of life in the PCS and significantly higher in the MCS compared to normative Swedish data. Clinical relevance The high prevalence of back pain, and the significant association between back pain daily or several times per week and severe or moderate disability on the RMDQ, and the negative correlation between RMDQ and SF-36, may have clinical relevance with regard to rehabilitation and follow-up of lower limb amputation.
Clear Sky Visibility Has Decreased over Land Globally from 1973 to 2007

Visibility in the clear sky is reduced by the presence of aerosols, whose types and concentrations have a large impact on the amount of solar radiation that reaches Earth's surface. Here we establish a global climatology of inverse visibilities over land from 1973 to 2007 and interpret it in terms of changes in aerosol optical depth and the consequent impacts on incident solar radiation. The aerosol contribution to “global dimming,” first reported in terms of strong decreases in measured incident solar radiation up to the mid-1980s, has monotonically increased over the period analyzed. Since that time, visibility has increased over Europe, consistent with reported European “brightening,” but has decreased substantially over south and east Asia, South America, Australia, and Africa, resulting in net global dimming over land.
Laptop Programs for Students

With the continuing decline in costs of technology, programs are proliferating worldwide to put networked laptop computers into the hands of millions of students on a routine basis. The reasons policy-makers support these programs are based on economic arguments, equity concerns, and widespread interest in education reform. Studies of laptop programs in schools report that they increase students' engagement in school, improve technology skills, and have positive effects on students' writing. However, evidence of the effectiveness of large-scale laptop programs in other learning domains is scarce. Research in many nations suggests that laptop programs will be most successful as part of balanced, comprehensive initiatives that address changes in education goals, curricula, teacher training, and assessment.
Use of digital technologies for nasal prosthesis manufacturing

Background and aim: Digital technology is becoming more accessible for common use in medical applications; however, their expansion in prosthetic and orthotic laboratories is not large because of the persistent image of difficult applicability to real patients. This article aims to offer real example in the area of human facial prostheses. Technique: This article describes the utilization of optical digitization, computational modelling, rapid prototyping, mould fabrication and manufacturing of a nasal silicone prosthesis. This technical note defines the key points of the methodology and aspires to contribute to the introduction of a certified manufacturing procedure. Discussion: The results show that the used technologies reduce the manufacturing time, reflect patient’s requirements and allow the manufacture of high-quality prostheses for missing facial asymmetric parts. The methodology provides a good position for further development issues and is usable for clinical practice. Clinical relevance Utilization of digital technologies in facial prosthesis manufacturing process can be a good contribution for higher patient comfort and higher production efficiency but with higher initial investment and demands for experience with software tools.
Mechanically Activated Integrin Switch Controls α5β1 Function

The cytoskeleton, integrin-mediated adhesion, and substrate stiffness control a common set of cell functions required for development and homeostasis that are often deranged in cancer. The connection between these mechanical elements and chemical signaling processes is not known. Here, we show that α5β1 integrin switches between relaxed and tensioned states in response to myosin II–generated cytoskeletal force. Force combines with extracellular matrix stiffness to generate tension that triggers the integrin switch. This switch directly controls the α5β1-fibronectin bond strength through engaging the synergy site in fibronectin and is required to generate signals through phosphorylation of focal adhesion kinase. In the context of tissues, this integrin switch connects cytoskeleton and extracellular matrix mechanics to adhesion-dependent motility and signaling pathways.
Structural Basis of Transcription: Backtracked RNA Polymerase II at 3.4 Angstrom Resolution

Stepping Back to Go Forward Insight into the mechanism of transcription has come from crystal structures of actively transcribing RNA polymerase II complexes in the pre- and posttranslocation states. RNA polymerase also backtracks on the DNA template. Backtracking by only a few residues is reversible, but longer backtracking leads to arrest that is relieved by cleavage of the transcript by the transcription elongation factor SII (TFIIS). Now Wang et al. (p. 1203) report x-ray structures of backtracked ternary complexes and of a backtracked complex bound to a noncleaving mutant of TFIIS. The structures show a defined one-residue, backtracked state supporting the idea that RNA polymerase oscillates between backward and forward motion during active transcription. Mismatched residues disfavor forward translocation, increasing the lifetime of the backtracked state and facilitating cleavage by TFIIS. Thus, TFIIS-induced cleavage is likely to provide an important proofreading function during transcription. A backtracked RNA polymerase II reveals how the enzyme proofreads the RNA transcript. Transcribing RNA polymerases oscillate between three stable states, two of which, pre- and posttranslocated, were previously subjected to x-ray crystal structure determination. We report here the crystal structure of RNA polymerase II in the third state, the reverse translocated, or “backtracked” state. The defining feature of the backtracked structure is a binding site for the first backtracked nucleotide. This binding site is occupied in case of nucleotide misincorporation in the RNA or damage to the DNA, and is termed the “P” site because it supports proofreading. The predominant mechanism of proofreading is the excision of a dinucleotide in the presence of the elongation factor SII (TFIIS). Structure determination of a cocrystal with TFIIS reveals a rearrangement whereby cleavage of the RNA may take place.
LXR Regulates Cholesterol Uptake Through Idol-Dependent Ubiquitination of the LDL Receptor

Idolizing Cholesterol Control The low-density lipoprotein receptor (LDLR) removes LDL, the so-called “bad” cholesterol particles, from the blood through a mechanism that involves LDL binding and internalization into liver cells. Because the LDLR plays a pivotal role in heart disease risk, there is substantial interest in understanding how its expression is regulated, and a large body of previous work has established the importance of transcriptional control. A new study identifies a signaling pathway that appears to regulate the LDLR at the level of protein degradation. Zelcer et al. (p. 100, published online 11 June) show that a sterol-responsive transcription factor called LXR induces the expression of Idol (for inducible degrader of the LDLR), a protein that triggers ubiquitination of the receptor and targets it for degradation. Activation of this pathway suppresses cellular uptake of LDL and, in a mouse model, leads to higher plasma LDL levels, raising the possibility that the pathway could be targeted pharmacologically to control plasma cholesterol levels. Cholesterol metabolism is regulated by a signaling pathway that targets the LDL receptor for degradation. Cellular cholesterol levels reflect a balance between uptake, efflux, and endogenous synthesis. Here we show that the sterol-responsive nuclear liver X receptor (LXR) helps maintain cholesterol homeostasis, not only through promotion of cholesterol efflux but also through suppression of low-density lipoprotein (LDL) uptake. LXR inhibits the LDL receptor (LDLR) pathway through transcriptional induction of Idol (inducible degrader of the LDLR), an E3 ubiquitin ligase that triggers ubiquitination of the LDLR on its cytoplasmic domain, thereby targeting it for degradation. LXR ligand reduces, whereas LXR knockout increases, LDLR protein levels in vivo in a tissue-selective manner. Idol knockdown in hepatocytes increases LDLR protein levels and promotes LDL uptake. Conversely, adenovirus-mediated expression of Idol in mouse liver promotes LDLR degradation and elevates plasma LDL levels. The LXR-Idol-LDLR axis defines a complementary pathway to sterol response element–binding proteins for sterol regulation of cholesterol uptake.
Synchronous Hyperactivity and Intercellular Calcium Waves in Astrocytes in Alzheimer Mice

Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium was globally elevated in the astrocytic network, but was independent of proximity to individual plaques. Time-lapse imaging revealed that calcium transients in astrocytes were more frequent, synchronously coordinated across long distances, and uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-β plaques, originating near plaques and spreading radially at least 200 micrometers. Thus, although neurotoxicity is observed near amyloid-β deposits, there exists a more general astrocyte-based network response to focal pathology.
Adult Human Müller Glia Cells Are a Highly Efficient Source of Rod Photoreceptors

There is growing evidence that Müller glia cells (MGCs) might act as regenerative elements in injured retinas of fishes and amniotes. However, their differentiation potential in humans is yet unknown. We isolated Müller glia from adult human retinas and propagated them in vitro revealing for the first time their ability to differentiate into rod photoreceptors. These results were also confirmed with mice retinas. Here, we describe conditions by which human MGCs adopt a rod photoreceptor commitment with a surprising efficiency as high as 54%. Functional characterization of Müller glia‐derived photoreceptors by patch‐clamp recordings revealed that their electrical properties are comparable to those of adult rods. Interestingly, our procedure allowed efficient derivation of MGC cultures starting from both injured and degenerating and postmortem human retinas. Human transplanted Müller glia‐derived photoreceptors integrate and survive within immunodeficient mouse retinas. These data provide evidence that Müller glia retains an unpredicted plasticity and multipotent potential into adulthood, and it is therefore a promising source of novel therapeutic applications in retinal repair. STEM CELLS 2011;29:344–356
Concise Review: Stem Cells for the Treatment of Cerebellar‐Related Disorders

Embryonic neural transplants have become clinically relevant over the past 25 years for their possible application in the treatment of cerebellum‐related neurodegenerative diseases. While highlighting the important role that fetal neural progenitors have in meeting these challenges, we define rationales for all types of cell therapy involving adult stem cells as well as human embryonic stem cells (hESC) and human induced pluripotent stem (iPS) cells. The recent advances in the field of hESC and iPS cells, including their capacity for differentiation toward regional specific neural lineages, could open a new era of transplantation in cell‐based therapy for cerebellar ataxias. STEM Cells 2011;29:564–569
Seismic Evidence for Sharp Lithosphere-Asthenosphere Boundaries of Oceanic Plates

Detection of the presence of melt at variable depth beneath two oceanic plates reveals the vertical extent of old oceanic plates. Boundary Issues of the Lithosphere The depth of Earth's tectonic plates is defined by the lithosphere-aesthenosphere boundary (LAB), but its seismic signature is more subtle compared with other deeper boundaries within Earth (see the Perspective by Romanowicz). Under oceanic plates, the LAB is often defined by where temperatures are hot enough to cause some melting. This boundary has been hard to detect in older oceanic plates, but it is important for understanding how these plates thicken with age or distance from ocean ridges, and for assessing heat flow through the oceanic crust. Kawakatsu et al. (p. 499) use a detailed seismic array to detect a seismic velocity reduction beneath the Philippine Sea and Pacific plates. The data imply that 5%, or less, melt forms horizontal layers, and that oceanic plate thicknesses do indeed deepen with age. Rychert and Shearer (p. 495) used 15 years of seismic data to explore the global distribution of an anomaly imaged by conversion of pressure waves to shear waves (waves associated with a sharp velocity drop). The data reveal a broad signal at depths of 70 kilometers (km) beneath ocean islands to 95 km beneath Precambrian shields. It is not clear whether this boundary is the lithosphere-aesthenosphere boundary or a layer with a distinct horizontal fabric. The mobility of the lithosphere over a weaker asthenosphere constitutes the essential element of plate tectonics, and thus the understanding of the processes at the lithosphere-asthenosphere boundary (LAB) is fundamental to understand how our planet works. It is especially so for oceanic plates because their relatively simple creation and evolution should enable easy elucidation of the LAB. Data from borehole broadband ocean bottom seismometers show that the LAB beneath the Pacific and Philippine Sea plates is sharp and age-dependent. The observed large shear wave velocity reduction at the LAB requires a partially molten asthenosphere consisting of horizontal melt-rich layers embedded in meltless mantle, which accounts for the large viscosity contrast at the LAB that facilitates horizontal plate motions.
Origin and Radiation of the Earliest Vascular Land Plants

Colonization of the land by plants most likely occurred in a stepwise fashion starting in the Mid-Ordovician. The earliest flora of bryophyte-like plants appears to have been cosmopolitan and dominated the planet, relatively unchanged, for some 30 million years. It is represented by fossilized dispersed cryptospores and fragmentary plant remains. In the Early Silurian, cryptospore abundance and diversity diminished abruptly as trilete spores appeared, became abundant, and underwent rapid diversification. This change coincides approximately with the appearance of vascular plant megafossils and probably represents the origin and adaptive radiation of vascular plants. We have obtained a diverse trilete spore occurrence from the Late Ordovician that suggests that vascular plants originated and diversified earlier than previously hypothesized, in Gondwana, before migrating elsewhere and secondarily diversifying.
ESSENTIAL ADVANCE CARE PLANNING: DEACTIVATION OF IMPLANTABLE CARDIOVERTER DEFIBRILLATORS (ICDS) AT END OF LIFE

Background Implantable cardioverter defibrillators (ICDs) reduce mortality in patients with certain cardiac conditions and are widely used in contemporary cardiac care. Increasingly, patients with ICDs are referred to palliative care services for management either of cardiac conditions, related co-morbidities or unrelated diseases. An ICD can have the defibrillator component deactivated thus avoiding futile and painful electrical shocks to the dying patient. Developing a strategy to sensitively manage deactivation of ICDs is an essential component of contemporary end of life/advance care planning. Aim To develop a strategy to ensure timely defibrillator deactivation in palliative patients across all environments of care. Methods Following a literature search concerning deactivation of ICDs, issues were explored in clinical meetings and workshop sessions. Stakeholders including cardiologists/electro-physiologists, specialist palliative care clinicians, general practitioners, lawyers, ethicists and patient liaison representatives drafted the strategy. Results The strategy was endorsed by Queensland Health, documented as a Clinical Practice Guideline and disseminated. It includes components relating to patient/relative wishes and history taking, communication between stakeholders, clinical alert notifications, procedures for emergency deactivation of devices, consent and documentation processes. Magnets for emergency use are located in palliative care units and doctors' medical bags. Discussion This inclusive strategy has decreased the risk of futile shocks in palliative patients in part by emphasising a particular component of advance care planning. It has been used successfully in acute, community and residential aged care settings. Conclusion Palliative care services need to adapt to contemporary clinical advances and incorporate such advances into the patients' advance care plans.
Quantification of rectifications for the Northwestern University Flexible Sub-Ischial Vacuum Socket

Background: The fit and function of a prosthetic socket depend on the prosthetist’s ability to design the socket’s shape to distribute load comfortably over the residual limb. We recently developed a sub-ischial socket for persons with transfemoral amputation: the Northwestern University Flexible Sub-Ischial Vacuum Socket. Objective: This study aimed to quantify the rectifications required to fit the Northwestern University Flexible Sub-Ischial Vacuum Socket to teach the technique to prosthetists as well as provide a computer-aided design–computer-aided manufacturing option. Study Design: Development project. Methods: A program was used to align scans of unrectified and rectified negative molds and calculate shape change as a result of rectification. Averaged rectifications were used to create a socket template, which was shared with a central fabrication facility engaged in provision of Northwestern University Flexible Sub-Ischial Vacuum Sockets to early clinical adopters. Feedback regarding quality of fitting was obtained. Results: Rectification maps created from 30 cast pairs of successfully fit Northwestern University Flexible Sub-Ischial Vacuum Sockets confirmed that material was primarily removed from the positive mold in the proximal-lateral and posterior regions. The template was used to fabricate check sockets for 15 persons with transfemoral amputation. Feedback suggested that the template provided a reasonable initial fit with only minor adjustments. Conclusion: Rectification maps and template were used to facilitate teaching and central fabrication of the Northwestern University Flexible Sub-Ischial Vacuum Socket. Minor issues with quality of initial fit achieved with the template may be due to inability to adjust the template to patient characteristics (e.g. tissue type, limb shape) and/or the degree to which it represented a fully mature version of the technique. Clinical relevance Rectification maps help communicate an important step in the fabrication of the Northwestern University Flexible Sub-Ischial Vacuum Socket facilitating dissemination of the technique, while the average template provides an alternative fabrication option via computer-aided design–computer-aided manufacturing and central fabrication.
A Functional Role for Transposases in a Large Eukaryotic Genome

Editing the Genome The ciliate Oxytricha trifallax has an unusual genome with the coding regions of genes (the exons) scattered through the genome. The exons are then somehow knitted together following transcription prior to their translation into proteins. As part of this process Oxytricha eliminates all transposable elements, stripping the genome down to 5% of the original germline DNA during development. Nowacki et al. (p. 935, published online 16 April) show that germline-limited transposases appear to be important for these large-scale DNA rearrangements. The ciliate Oxytricha expresses transposase genes to influence thousands of DNA rearrangements required for proper development. Despite comprising much of the eukaryotic genome, few transposons are active, and they usually confer no benefit to the host. Through an exaggerated process of genome rearrangement, Oxytricha trifallax destroys 95% of its germline genome during development. This includes the elimination of all transposon DNA. We show that germline-limited transposase genes play key roles in this process of genome-wide DNA excision, which suggests that transposases function in large eukaryotic genomes containing thousands of active transposons. We show that transposase gene expression occurs during germline-soma differentiation and that silencing of transposase by RNA interference leads to abnormal DNA rearrangement in the offspring. This study suggests a new important role in Oxytricha for this large portion of genomic DNA that was previously thought of as junk.