Miracle-dz/UniFAR-FTUs huggingface dataset:
The Membrane-bound GTPase Guf1 Promotes Mitochondrial Protein Synthesis under Suboptimal Conditions*

Recently, the bacterial elongation factor LepA was identified as critical for the accuracy of in vitro translation reactions. Extremely well conserved homologues of LepA are present throughout bacteria and eukaryotes, but the physiological relevance of these proteins is unclear. Here we show that the yeast counterpart of LepA, Guf1, is located in the mitochondrial matrix and tightly associated with the inner membrane. It binds to mitochondrial ribosomes in a GTP-dependent manner. Mutants lacking Guf1 show cold- and heat-sensitive growth defects on non-fermentable carbon sources that are especially pronounced under nutrient-limiting conditions. The cold sensitivity is explained by diminished rates of protein synthesis at low temperatures. At elevated temperatures, Guf1-deficient mutants exhibit defects in the assembly of cytochrome oxidase, suggesting that the polypeptides produced are not functional. Moreover, Guf1 mutants exhibit synthetic growth defects with mutations of the protein insertase Oxa1. These observations show a critical role for Guf1 in vivo. The observed defects in Guf1-deficient mitochondria are consistent with a function of Guf1 as a fidelity factor of mitochondrial protein synthesis.
Ultrasonic damage assessment of articular cartilage for ultrasonic drug delivery

Osteoarthritis (OA) is a common musculoskeletal disease. There are drug therapies under development, but no localized way to transfer drugs into articular cartilage (AC). Previously we showed that 20 kHz high intensity ultrasound (HIU) can deliver micro- and nano-particles into AC [1]. However, at low frequencies, cavitation may occur. Our hypothesis is that 20 MHz ultrasound pulse-echo can be used to track changes in ultrasound reflection from AC during HIU. Here we tested the feasibility of this approach for characterizing cavitation-related damage. We observed that the relative decrease in mean surface reflection coefficient at 15, 20 and 25 MHz were -40.9 +/- 7.9 %, -53.4 +/- 12.0 % and -61.1 +/- 7.1 %, respectively, during a 5-minute HIU exposure. Frequencies above 16 MHz were the most sensitive to changes induced by HIU in both samples. We propose that the change resulted from cavitation-related cratering of the AC surface and exposure of AC tissue with lower collagen content. In conclusion, the acoustic reflection coefficient of the AC surface could be a sensitive parameter to estimate damage in the AC surface during HIU exposure.
Even moderate chronic renal failure is associated with impaired acute and long‐term outcome after coronary angioplasty

SUMMARY: End‐stage renal failure requiring maintenance haemodialysis is known to be a strong independent predictor of mortality and complications after coronary interventions. In contrast, data about the outcome of patients with moderate chronic renal failure is very limited and was therefore evaluated in this study in patients with coronary angioplasty (PTCA). This was a retrospective case‐control study of 66 patients with moderate chronic renal failure who underwent PTCA, and who were matched to 66 PTCA patients with normal renal function and followed up by telephone interviews. In hospital, patients with renal failure suffered significantly more often from local complications (12.1 vs 0%, P = 0.004) and acute deterioration of renal function after PTCA (7.6 vs 0%, P = 0.023) than their matched controls. Angiographic success after PTCA was not significantly different (85 vs 83%, n.s.) as was the case with in‐hospital mortality (6.1 vs 3.0%, n.s.). During follow up (100% complete), 18 patients (27.3%) with renal failure had died compared with seven controls (10.6%; OR 3.2, P = 0.015). Even if deaths from non‐cardiac causes in three patients with renal failure were excluded, death after PTCA occurred significantly more often in the renal failure group (P = 0.015, log rang test). Multivariate analyses with stepwise logistic regression identified impaired left ventricular function (OR 2.24, 95%CI 1.33–3.77), elevated serum creatinine (OR 2.02, 95%CI 1.24–3.31) and smaller height (OR 0.91, 95%CI 0.86–0.98) to be independently associated with death. In conclusion, in this matched‐pair study, patients with chronic renal failure suffered from more in‐hospital complications and from markedly increased long‐term mortality after PTCA.
Constraint satisfaction problems in clausal form: Autarkies and minimal unsatisfiability

We consider the problem of generalising boolean formulas in conjunctive normal form by allowing non-boolean variables, where our goal is to maintain combinatorial properties. Requiring that a literal involves only a single variable, the most general form of literals is given by the well-known “signed literals”, however we will argue that only the most restricted form of generalised clause-sets, corresponding to “sets of no-goods” in the AI literature, maintains the essential properties of boolean conjunctive normal forms. We start our investigations by building up a solid foundation for (generalised) clause-sets, including the notion of autarky systems, the interplay between autarkies and resolution, and basic notions of (DP-)reductions. As a basic combinatorial parameter of generalised clause-sets, we introduce the (generalised) notion of deficiency, which in the boolean case is the difference between the number of clauses and the number of variables. We obtain fixed parameter tractability (FPT) of satisfiability decision for generalised clause-sets, using as parameter the maximal deficiency (over all sub-clause-sets). Another central result in the boolean case regarding the deficiency is the classification of minimally unsatisfiable clause-sets with low deficiency (MU(1), MU(2), . ). We generalise the well-known characterisations of boolean MU(1). The proofs for FPT and MU(1) are not straight-forward, but are obtained by an interplay between suitable generalisations of techniques and notions from the boolean case, and exploiting combinatorial properties of the natural translation of (generalised) clause-sets into boolean clause-sets. Of fundamental importance here is autarky theory, and we concentrate especially on matching autarkies (based on matching theory). A natural question considered here is to determine the structure of (matching) lean clause-sets, which do not admit non-trivial (matching) autarkies. Special lean clause-sets are minimally unsatisfiable (generalised) clause-sets, and we consider the generalisation to irredundant clause-sets, so that also satisfiable clause-sets can be taken into account, with a special emphasise on hitting clause-sets (which are irredundant in a very strong sense) and the generalisation to multihitting clause-sets. Supported by EPSRC Grant GR/S58393/01 1 Electronic Colloquium on Computational Complexity, Report No. 55 (2007)
Wirksamkeit der beruflichen Erwachsenenbildung

"In diesem Beitrag wird anhand von Daten aus verschiedenen Quellen (Zusatzbefragung zum Mikrozensus 1970 des Statistischen Bundesamtes, Geschaftsstatistiken der Bundesanstalt fur Arbeit sowie Wirksamkeitsanalysen des Instituts fur Arbeitsmarkt- und Berufsforschung der Bundesanstalt fur Arbeit) ein Uberblick uber die Entwicklung und die Wirksamkeit der beruflichen Erwachsenenbildung in der Bundesrepublik Deutschland ergeben. Dabei werden vor allem folgende Fragen behandelt: - Entspricht die Struktur der Teilnehmer an Masnahmen der beruf lichen Erwachsenenbildung der Intention des Gesetzgebers? - Wie hoch ist der Anteil der Personen, die eine solche Mas nahme mit Erfolg abschliesen? - In welchem Ausmas gelingt die fortbildungs- bzw. umschulungs adaquate Eingliederung in das Erwerbsleben nach Abschlus der Masnahme? Die Analyse brachte folgende Ergebnisse: 1. Etwa 40 Prozent aller Teilnehmer an Masnahmen der beruflichen Erwachsenenbildung werden durch die Bundesanstalt fur Arbeit finanziell gefordert. 2. Derzeit ist etwa ein Viertel aller mannlichen und die Halfte aller weiblichen (geforderten) Teilnehmer an beruflichen Bildungsmasnahmen vor Beginn der Masnahme arbeitslos. 3. Personen mit niedrigem allgemeinen Bildungsniveau, Frauen, altere Personen und Arbeiter sind unter den Teilnehmern an beruflichen Bildungsmasnahmen unterreprasentiert. Es zeigt sich allerdings, das die staatlich geforderte berufliche Erwachsenenbildung diese Personenkreise in uberdurchschnittlichem Mase erfast. 4. Der Anteil der Personen, die eine (staatlich geforderte) Masnahme der beruflichen Erwachsenenbildung abbrechen oder ohne Erfolg beenden, liegt bei eta 20%. 5. Insbesondere die betriebliche Einarbeitung hat sich als wirksames Mittel zur Eingliederung von Arbeitslosen in das Erwerbsleben erwiesen: Von den Teilnehmern an Masnahmen der betrieblichen Einarbeitung waren vor Beginn der Masnahme uber 50% arbeitslos, nach Abschlus der Masnahme lag der Anteil der Arbeitslosen bei etwa 1 %. 6. Ahnliche Ergebnisse zeigten sich auch bei den Fortbildungsmasnahmen mit dem Ziel der Anpassung und Vertiefung der beruflichen Kenntnisse und Fertigkeiten im Bereich der gewerblichen Berufe. 7. Von den (erfolgreichen) Teilnehmern an aufstiegsbezogenen Fortbildungsmasnahmen waren nach Abschlus der Masnahme zwischen 70 und 80 % (voll oder teilweise) fortbildungsadaquat beschaftigt. Ahnliche Erfolgsquoten zeigten sich auch bei der Umschulung Behinderter: Drei Viertel waren anschliesend im Umschulungsberuf beschaftigt. "
Reduction in Cerebral Oxygenation due to Patent Ductus Arteriosus Is Pronounced in Small-for-Gestational-Age Neonates

Background: A haemodynamically significant patent ductus arteriosus (hsPDA) reduces cerebral oxygenation in appropriate-for-gestational-age (AGA) preterm neonates. Reduced cerebral oxygenation has been associated with brain injury. Preterm small-for-gestational-age (SGA) neonates show higher cerebral oxygenation than AGA peers throughout the first postnatal days. To date, no studies have investigated the effect of hsPDA on cerebral oxygenation in preterm SGA neonates. Objective: We aimed to assess the effect of hsPDA on cerebral oxygenation in preterm SGA neonates compared to AGA peers. We hypothesised that higher baseline cerebral oxygenation would reduce the impact of hsPDA on cerebral oxygenation in preterm SGA neonates. Methods: We monitored regional cerebral oxygen saturation (rScO2) with near-infrared spectroscopy and calculated the cerebral fractional tissue oxygen extraction (cFTOE) for 72 h after birth. Retrospective analysis compared 36 preterm SGA neonates (birth weight <10th percentile, 18 with hsPDA) to 36 preterm AGA neonates (birth weight 20th to 80th percentile, 18 with hsPDA). Results: In contrast to the other groups, SGA-hsPDA neonates demonstrated a significant fall in rScO2 [69% (SEM 2.5) at 4-8 h to 61% (2.7) at 68-72 h, p < 0.001] with a concurrent rise in cFTOE [0.26 (0.026) at 4-8 h to 0.34 (0.030) at 68-72 h, p < 0.001]. Conclusions: Contrary to our hypothesis, hsPDA had a significant negative effect on cerebral oxygenation in preterm SGA neonates. Future studies should explore the potential benefits of early screening and treatment for hsPDA on long-term neurodevelopmental outcome in preterm SGA neonates.
Mastery and Depressive Symptoms: How Does Mastery Influence the Impact of Stressors From Midlife to Old Age?

Objective: The objective of this research is to study depressive symptoms (DS) among adults aged 40 to 79 years and examine how mastery influences the impact of sociodemographic, socioeconomic, and health factors on DS. Method: We used a sample of the Norwegian Life Course, Generation, and Gender (LOGG) study (N = 6,879) and analyzed how mastery influences the independent variables on DS via regression analyses. Results: Mastery affected DS directly and influenced the effects of sociodemographic, socioeconomic, and health factors on DS. There was a stronger relationship between stressors and DS among respondents with low than high mastery. DS were most prevalent among people aged 70 to 79 years. When mastery was also controlled for, the oldest group (70-79 years) had significantly fewer DS than those aged 40 to 49 years. Discussion: The influence of mastery and stressors on DS seems to vary along the life span. The result that mastery was a relatively stronger buffer against DS in midlife than in old age is discussed.
Increased quantal release of acetylcholine at the neuromuscular junction following scald injury in the rat

Following severe burns, patients frequently develop a profound resistance to nondepolarizing neuromuscular blockers. Several mechanisms have been proposed to account for this, including upregulation of nicotinic acetylcholine receptors. We investigated the effects of a 30% body surface area (BSA) scald on neuromuscular transmission in slow‐twitch soleus (SOL) and fast‐twitch extensor digitorum longus (EDL) of rats. Rats were sacrificed 72 h after the injury, a time at which sepsis is unlikely and body weight gain and core temperature have returned to normal. Further groups of rats were sham operated and either pair fed to the scalded rats or freely fed to assess the influence of food restriction. When compared with muscle from pair‐fed control rats, scald resulted in an almost 50% increase in miniature endplate potential (mEPP) frequency in both SOL and EDL. However, scald did not increase mean mEPP amplitude in SOL, although it did cause a 10% increase in EDL. Scald injury did produce a significant increase in the size of the evoked endplate potential in SOL (33%) and EDL (37%). These data indicate that a significant increase in the quantal content of evoked transmitter released in SOL (38%) and EDL (30%) occurred by 72 h after scald. Such an increase may contribute to the resistance to nondepolarizing neuromuscular blockers documented in patients following thermal injury. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 1660–1666, 1999
Targeted Antifungal Prophylaxis in Heart Transplant Recipients

Background Antifungal prophylaxis after heart transplantation is usually targeted to high-risk recipients, but the duration is normally fixed and empirical. Our purpose was to assess the efficacy of a personalized prophylactic approach based on the duration of the risk factors. Methods In a prospective cohort, from 2003 to 2010, prophylaxis was only administered to patients with risk factors (13 of 133) and duration was personalized, starting with the risk factor and continued a median of 20 days after its resolution. Results Antifungal prophylaxis was prescribed only in 9.8% of the recipients and was effective in all but one patient who should have received a higher dose of caspofungin due to his obesity. Despite suffering an outbreak of invasive aspergillosis (IA) in the intensive care unit due to extremely high concentration of spores in the air (three cases with no personal risk factors), there was a reduction in the incidence of IA (8.6% vs. 2.2%; P=0.01) and Aspergillus-related mortality (5.75% vs. 1.5%; P=0.06). Conclusions Targeted prophylaxis for IA in heart recipients provided only to patients with risk factors and maintained for a median of 20 days after their disappearance is effective and safe. A high environmental load of Aspergillus spores in the intensive care unit would also indicate the need for antifungal prophylaxis in all exposed patients.
Impacto biomolecular de la terapia transfusional

La terapia transfusional ha evolucionado a grandes pasos para benefi cio de los pacientes. Durante la primera mitad del siglo XX las principales complicaciones eran de origen inmunologico: las reacciones hemoliticas graves por incompatibilidad de grupo o Rh se presentaban hasta en 1 de cada 500 transfusiones. Despues fueron las complicaciones infecciosas las que amenazaban la vida de los receptores. Una mejor seleccion de donadores y estudios de escrutinio de la sangre donada lograron reducir de forma notable los riesgos de infecciones asociadas con el VIH y el virus de hepatitis B y C. Actualmente, la probabilidad de una reaccion hemolitica grave por incompatibilidad es de 1 por cada 40 a 70 mil, y el riesgo de transmision de infecciones virales es bajisimo (Cuadro I). Se han comprendido mejor cuales son los cambios a nivel bioquimico, molecular e inmunologico, y como estos pueden impactar en el pronostico de los enfermos, e ironicamente, cuando los problemas inmunologicos parecian controlados, nuevas complicaciones de este tipo han sido detectadas. Los anestesiologos estamos involucrados con mucha frecuencia en el manejo de los productos hematicos, por lo que es necesario que seamos expertos en el empleo y posibles complicaciones asociadas del uso de la sangre y sus derivados. Lesion aguda pulmonar asociada con la transfusion (TRALI por sus iniciales en ingles). TRALI es una complicacion que ha sido poco reconocida y por lo mismo, poco reportada. Solo se empezo a detectar en la decada de los 90 y hasta el 2004 se desarrollaron los criterios diagnosticos que la defi nen (Cuadro II). Clinicamente se caracteriza por el desarrollo de edema pulmonar no cardiogenico dentro de las primeras seis horas de la transfusion. Su frecuencia va de 0.04 hasta el 8% de los pacientes transfundidos, dependiendo del tipo de poblacion estudiada, con la frecuencia mayor en los pacientes en estado critico(1,2). Recientemente se reporto un estudio que analiza la poblacion quirurgica no cardiaca(3), en donde la frecuencia
Infliximab Inhibits Activation and Effector Functions of Peripheral Blood T Cells in vitro from Patients with Clinically Active Ulcerative Colitis

Many patients with inflammatory bowel disease (IBD) are undergoing therapy with infliximab, an antibody specific for TNF. However, the exact mechanisms of action of infliximab are not completely understood. The aim of this study was to determine the in vitro effects of infliximab on blood T cells derived from anti‐TNF therapy–naïve ulcerative colitis (UC) patients with clinically active disease. Peripheral blood mononuclear cells were stimulated polyclonally or by antigen in the presence or absence of infliximab. The T cell phenotype was investigated by flow cytometry, cytokine secretion was determined by ELISA, and cell proliferation was determined by thymidine assay or CFSE dye. Presence of infliximab resulted in reduced expression of CD25 in CD4+ and CD8+ T cell populations and inhibited secretion of IFN‐γ, IL‐13, IL‐17A, TNF as well as granzyme A. Infliximab also suppressed CD4+ and CD8+ T cell proliferation. These effects of infliximab were recorded both in T cells activated by polyclonal and antigen‐specific stimulation. The effects of infliximab on T cell apoptosis and induction of FOXP3+CD4+ T regulatory cells were ambiguous and depended on the originating cellular source and/or the stimulation mode and strength. In conclusion, infliximab is able to reduce T cell activation as measured by CD25, proliferation and cytokine secretion in vitro from UC patients with clinically active disease. These data suggest that suppression of T cell activity may be important for infliximab‐mediated disease remission in patients with UC.
MORPHOLOGIC CHARACTERISTICS OF CHRONIC MACULAR HOLE ON OPTICAL COHERENCE TOMOGRAPHY

Purpose: To investigate the morphologic characteristics of chronic macular holes (MHs) using optical coherence tomography. Methods: We retrospectively reviewed optical coherence tomographic images of consecutive patients who had been diagnosed with MH. Chronic MH was defined as MH that was observed without being surgically treated for at least 1 year. Optical coherence tomographic parameters were compared between chronic and acute MH. Results: Thirteen eyes of 13 patients were classified as chronic MH, and 67 eyes of 67 patients were classified as controls. While the basal hole diameter of chronic MH was not different from that of controls (P = 0.146), the minimum hole diameter (781.8 &mgr;m) of chronic MH was larger than that of controls (448.4 &mgr;m; P < 0.001). The hole height and MH index were smaller in the chronic MH group (380.6 &mgr;m; 0.31) than in control group (469.9 &mgr;m, 0.53; P = 0.033, P = 0.003). Intraretinal fluid was less frequently observed in chronic MH than in controls (P < 0.001). Retinal pigment epithelial atrophy was only observed in chronic MH. Conclusion: Chronic MH has features distinct from those of acute symptomatic MH on optical coherence tomography. These findings provide useful insight for the differentiation of chronic MH from acute MH.
A Discharge Planning Template for the Electronic Medical Record Improves Scheduling of Neurology Follow-up for Comanaged Seizure Patients.

OBJECTIVE We examined whether the addition of a standardized discharge planning template (DPT) for the electronic medical record facilitated scheduling of outpatient neurology follow-up appointments in children hospitalized with seizures. METHODS We reviewed medical records of patients discharged from a children's hospital with a diagnosis of seizures between January 2012 and June 2013. The study cohort included children who were admitted to the hospitalist service with neurology service comanagement. To facilitate interdisciplinary communication around discharge planning, a DPT was added to the neurology consult note in July 2012. Multivariate regression was used to determine whether the postimplementation time period was associated with the primary outcome (scheduling of outpatient neurology follow-up before discharge). RESULTS The final cohort included 300 patients, of whom 101 (34%) were discharged before implementation of the DPT, and 199 (66%) were discharged postimplementation of the DPT. The odds of having a neurology follow-up appointment scheduled before discharge was significantly higher after implementation of the DPT (adjusted odds ratio 2.8, 95% confidence interval 1.7-4.8) and for weekday as compared with weekend discharges (adjusted odds ratio 2.2, 95% confidence interval 1.2-3.9). CONCLUSIONS A discharge planning template for the electronic medical record can standardize the flow of discharge-related information between disciplines and may help expedite transitional care planning for hospitalized children, especially those with multiple consultants involved in their care. Given the inherent barriers to arranging outpatient services over the weekend, additional strategies may be necessary to enhance transitional care planning for patients going home over the weekend.
Isolation and characterization of a UV-sensitive mutator (mutB1) mutant of Haemophilus influenzae

The mutB1 mutant of Haemophilus influenzae is very sensitive to UV radiation but only slightly sensitive to methylmethane sulfonate or N-methyl-N'-nitro-N-nitrosoguanidine. Cultures of mutB1 cells contain high numbers of spontaneous mutants and show hypermutability after exposure to the latter mutagen. Normally high-efficiency transforming markers, as well as low-efficiency ones, transform mutB1 recipients at similarly low efficiencies. Significant host cell reactivation was observed when mutB1 cells were exposed to UV-damaged phage; however, these mutants showed a decrease in phage recombination. This mutant did not degrade its DNA following exposure to UV. It is speculated that the mutB1 mutation is similar to the Escherichia coli uvrD mutation.
Progression from allergic sensitization to asthma

Asthma is one of the atopic diseases strongly associated with allergy. High aeroallergen exposure in the immediate postnatal period has been associated with higher risk of sensitization and chronic asthma. It is proposed that following in utero allergen sensitization, postnatal high dose allergen exposure localizes inflammation to the airways. In association with adjuvantizing effects of some virus infections, eosinophils and neutrophils are recruited which contribute to epithelial damage and the initiation of the remodelling process. Eventually, the latter processes lead to sufficient airway narrowing to manifest as the first symptoms of asthma. Thus, the immunopathology of asthma is fully established by the time of first symptoms and future strategies will need to identify those at risk of developing the disease before irreversible changes in the airways are established.