Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of an animal model of severe sepsis associated with respiratory dysfunction.

PURPOSE Pathophysiological studies in humans regarding sepsis are difficult to perform due to ethical and methodological concerns. In this context, animal models of sepsis can be useful to better understand this condition and to test therapeutic strategies. The purpose of this study was to characterize a feasible and clinically relevant model of sepsis in pigs that could be useful for testing different therapeutic interventions. METHODS 5 White Large pigs were anesthetized, arterial and pulmonary catheters were introduced, and sepsis was induced by fecal peritonitis. Several biochemical indicators of organ dysfunction and infectious parameters were measured. The pigs were monitored until death, when fragments of organs were removed for pathology. Three animals without peritonitis served as controls and were sacrificed 24 hours after surgery without developing significant changes in organ function. RESULTS Septic pigs survived 17 hours on average (range, 16-18 h), and Escherichia coli was recovered from blood cultures. They developed a significant decrease in left ventricular work and a nonsignificant reduction in mixed venous oxygen saturation. Respiratory dysfunction was characterized by a decrease in the PaO2/FiO2 ratio and respiratory compliance. Pathology of the lungs revealed areas of pulmonary collapse, hemorrhage, pulmonary congestion, and discrete neutrophil infiltrate. CONCLUSIONS Fecal peritonitis in pigs is a clinically relevant model of sepsis associated with acute lung injury without direct pulmonary insult. This model may prove to be useful for studying pathogenic aspects of secondary lung injury as well as for validating ventilatory or pharmacologic interventions.
4,5,6-Tri-O-acetyl-2,3-di-S-ethyl-2,3-dithio-d-allose diethyl dithioacetal

The title compound, C20H36O6S4, was obtained by ethanethiolysis of 3,5,6-tri-O-acetyl-1,2-O-isopropylidene-α-d-glucofuranose. One of the ethyl groups is disordered over two sites with refined occupancies of 0.869 (6) and 0.131 (6). Compared with the precursor, the absolute configuration of the stereocenters at positions C-3 and C-2 are inverted and maintained, respectively.
“Virus and Epidemic”: Causal Knowledge Activates Prediction Error Circuitry

Knowledge about cause and effect relationships (e.g., virus–epidemic) is essential for predicting changes in the environment and for anticipating the consequences of events and one's own actions. Although there is evidence that predictions and learning from prediction errors are instrumental in acquiring causal knowledge, it is unclear whether prediction error circuitry remains involved in the mental representation and evaluation of causal knowledge already stored in semantic memory. In an fMRI study, participants assessed whether pairs of words were causally related (e.g., virus–epidemic) or noncausally associated (e.g., emerald–ring). In a second fMRI study, a task cue prompted the participants to evaluate either the causal or the noncausal associative relationship between pairs of words. Causally related pairs elicited higher activity in OFC, amygdala, striatum, and substantia nigra/ventral tegmental area than noncausally associated pairs. These regions were also more activated by the causal than by the associative task cue. This network overlaps with the mesolimbic and mesocortical dopaminergic network known to code prediction errors, suggesting that prediction error processing might participate in assessments of causality even under conditions when it is not explicitly required to make predictions.
FD4: A framework for highly scalable load balancing and coupling of multiphase models

More and more detailed simulation codes are developed promoted by the growing capability of high performance computers and the increasing knowledge about the underlying processes. This includes multiphase and multiphysics simulations as well as the coupling of multidisciplinary models. This paper introduces the framework FD4 (Four‐Dimensional Distributed Dynamic Data structures), which enables highly scalable implementations of multiphase models. The separation of the data structures for the single phases allows the use of different partitionings and also dynamic load balancing, which is essential to efficiently utilize high performance computers. The application of FD4 for an atmospheric modeling system with a detailed description of cloud processes successfully eliminates the load imbalance with a moderate overhead of 5% at 32k processors.
Algorithm for neuropathic pain treatment: An evidence based proposal

New studies of the treatment of neuropathic pain have increased the need for an updated review of randomized, double-blind, placebo-controlled trials to support an evidence based algorithm to treat neuropathic pain conditions. Available studies were identiﬁed using a MEDLINE and EMBASE search. One hundred and ﬁve studies were included. Numbers needed to treat (NNT) and numbers needed to harm (NNH) were used to compare efﬁcacy and safety of the treatments in different neuropathic pain syndromes. The quality of each trial was assessed. Tricyclic antidepressants and the anticonvulsants gabapentin and pregabalin were the most frequently studied drug classes. In peripheral neuropathic pain, the lowest NNT was for tricyclic antidepressants, followed by opioids and the anticonvulsants gabapentin and pregabalin. For central neuropathic pain there is limited data. NNT and NNH are currently the best way to assess relative efﬁcacy and safety, but the need for dichotomous data, which may have to be estimated retrospectively for old trials, and the methodological complexity of pooling data from small cross-over and large parallel group trials, remain as limitations.
Prevalence and associated factors of COPD among Aboriginal peoples in Canada: a cross-sectional study

Background COPD among Aboriginal peoples in Canada is a major public health concern. This study was conducted in order to determine the prevalence and association between certain risk factors and COPD among the 35-year-old or older Aboriginal peoples in Canada. Methods This is a cross-sectional study. It uses data from Statistics Canada’s Aboriginal Peoples Survey (APS), 2012. It consists of 8,117 self-identified Aboriginal peoples, aged 35 years old or older from all Canadian provinces and territories. The study outcomes centered on evaluating the prevalence and associated factors of COPD. Results This study found that 6.80% of the participants self-reported having COPD. Results of the logistic regression analysis show that COPD was significantly higher among daily smokers (odds ratio [OR], 2.28; 95% confidence interval [95% CI], 1.65–3.14), aged 55 years or older (OR, 3.04; 95% CI, 2.14–4.30), who earned $5,000–$9,999 per annum (OR, 4.21; 95% CI, 2.39–7.41) and needed health care over the past 12 months and did not receive it (OR, 1.83; 95% CI, 1.27–2.65). Conclusion The findings of our study show that COPD is strongly associated with Aboriginal peoples, who are older, smoke, have a low socioeconomic status (SES) and do not have access to health care when needed. Clinicians, health care professionals, medical/public health organizations, researchers and patients will greatly benefit from additional research in this common, serious and often overlooked disease among Aboriginal peoples in Canada.
Recognition of Double-Stranded RNA and Regulation of Interferon Pathway by Toll-Like Receptor 10

Toll-like receptor (TLR)-10 remains an orphan receptor without well-characterized ligands or functions. Here, we reveal that TLR10 is predominantly localized to endosomes and binds dsRNA in vitro at endosomal pH, suggesting that dsRNA is a ligand of TLR10. Recognition of dsRNA by TLR10 activates recruitment of myeloid differentiation primary response gene 88 for signal transduction and suppression of interferon regulatory factor-7 dependent type I IFN production. We also demonstrate crosstalk between TLR10 and TLR3, as they compete with each other for dsRNA binding. Our results suggest for the first time that dsRNA is a ligand for TLR10 and propose novel dual functions of TLR10 in regulating IFN signaling: first, recognition of dsRNA as a nucleotide-sensing receptor and second, sequestration of dsRNA from TLR3 to inhibit TLR3 signaling in response to dsRNA stimulation.
Risk factors for reduced glomerular filtration rate in a Nicaraguan community affected by Mesoamerican nephropathy.

INTRODUCTION Mesoamerican nephropathy, also known as chronic kidney disease of unknown etiology, is widespread in Pacific coastal Central America. The cause of the epidemic is unknown, but the disease may be linked to multiple factors, including diet as well as environmental and occupational exposures. As many as 50% of men in some communities have Mesoamerican nephropathy. OBJECTIVE Describe prevalence of reduced glomerular filtration rate in a region of Nicaragua suspected to harbor high rates of Mesoamerican nephropathy; and investigate potential risk factors for such reduction associated with agricultural work (such as pesticide exposure and specific agricultural tasks associated with increased heat stress); sugar consumption; and traditional factors such as age, sex, diabetes, hypertension and nephrotoxic medication use. METHODS This study uses a cross-sectional design with nested case-control analysis. Cases were individuals with estimated glomerular filtration rates of <60mL/min/1.73m2 and controls were individuals with those >90mL/min/1.73m2, estimated using serum creatinine. Data on nutrition, past medical history, medication and substance use, and agricultural behaviors and exposures were collected using medical questionnaires from June through August, 2012. Venous blood and urine samples were collected to assess hemoglobin A1c, and dipstick proteinuria, respectively; anthropometry and blood pressure measurements were made using standard techniques. Analyses were conducted using chi square, and univariate and multiple logistic regression. RESULTS Of 424 individuals in the study, 151 had an occupational history in agriculture. Prevalence of glomerular filtration rate <60mL/min/1.73m2 was 9.8% among women and 41.9% among men (male to female ratio = 4.3, p<0.0001). Proteinuria =300 mg/dL was observed in <10% of participants with decreased glomerular filtration rate. Hemoglobin A1c and use of NSAIDs were not associated with decreased glomerular filtration rate. Although systolic and diastolic blood pressure was higher among participants with decreased glomerular filtration rate (p <0.001), hypertension was uncommon. Significant agricultural risk factors for reduced glomerular filtration rate included increased lifetime days cutting sugarcane during the dry season (OR 5.86, 95% CI 2.45-14.01), nondeliberate pesticide inhalation (OR 3.31, 95% CI 1.32-8.31), and sugarcane chewing (OR 3.24, 95% CI 1.39-7.58). CONCLUSIONS Our findings demonstrate a high prevalence of chronic kidney disease not linked to traditional risk factors, and suggest it may be associated instead with occupational exposure to heat stress in conjunction with pesticide inhalation, sugarcane chewing and sugar intake during the workday.
Two novel peripheral membrane proteins, pasin 1 and pasin 2, associated with Na+,K(+)-ATPase in various cells and tissues

Purification of pig kidney Na+,K(+)-ATPase at low concentrations of SDS (0.5%) allowed copurification of several peripheral membrane proteins. Some of these associated proteins were identified as components of the membrane cytoskeleton. Here we describe two novel globular proteins of of Mr 77,000 (pasin 1) and Mr 73,000 (pasin 2) which copurify and coimmunoprecipitate with Na+,K(+)-ATPase and can be stripped off Na+,K(+)-ATPase microsomes by 1 M KCl. Pasin 1 and pasin 2 were detected by immunoblot analysis in various cells and tissues including erythrocytes and platelets. Immunostaining revealed colocalization of pasin 1 and Na+,K(+)-ATPase along the basolateral cell surface of epithelial cells of kidney tubules and parotid striated ducts (titers of pasin 2 antibodies were too weak for immunocytochemistry). In erythrocytes, pasin 1 and pasin 2 are minor components bound to the cytoplasmic surface of the plasma membrane. Pasin 1 showed the same electrophoretic mobility as protein 4.1b. However, both proteins have different isoelectric points (pasin 1, pI 6; protein 4.1, pI 7), different chymotryptic fragments, and are immunologically unrelated. Short pieces of sequence obtained from pasin 1 and pasin 2 were not found in any other known protein sequence. The occurrence of pasin 1 and pasin 2 in diverse cells and tissues and their association with Na+,K(+)-ATPase suggests a general role of these proteins in Na+,K(+)- ATPase function.
The usefulness of lean six sigma to the development of a clinical pathway for hip fractures.

AIMS AND OBJECTIVES The objective of this study was to show the usefulness of lean six sigma (LSS) for the development of a multidisciplinary clinical pathway. METHODS A single centre, both retrospective and prospective, non-randomized controlled study design was used to identify the variables of a prolonged length of stay (LOS) for hip fractures in the elderly and to measure the effect of the process improvements--with the aim of improving efficiency of care and reducing the LOS. RESULTS The project identified several variables influencing LOS, and interventions were designed to improve the process of care. Significant results were achieved by reducing both the average LOS by 4.2 days (-31%) and the average duration of surgery by 57 minutes (-36%). The average LOS of patients discharged to a nursing home reduced by 4.4 days. CONCLUSION The findings of this study show a successful application of LSS methodology within the development of a clinical pathway. Further research is needed to explore the effect of the use of LSS methodology at clinical outcome and quality of life.
An Empirical Analysis of Search in GSAT

We describe an extensive study of search in GSAT, an approximation procedure for propositional satisfiability. GSAT performs greedy hill-climbing on the number of satisfied clauses in a truth assignment. Our experiments provide a more complete picture of GSAT's search than previous accounts. We describe in detail the two phases of search: rapid hill-climbing followed by a long plateau search. We demonstrate that when applied to randomly generated 3-SAT problems, there is a very simple scaling with problem size for both the mean number of satisfied clauses and the mean branching rate. Our results allow us to make detailed numerical conjectures about the length of the hill-climbing phase, the average gradient of this phase, and to conjecture that both the average score and average branching rate decay exponentially during plateau search. We end by showing how these results can be used to direct future theoretical analysis. This work provides a case study of how computer experiments can be used to improve understanding of the theoretical properties of algorithms.
The Golgi-Associated Hook3 Protein Is a Member of a Novel Family of Microtubule-Binding Proteins

Microtubules are central to the spatial organization of diverse membrane-trafficking systems. Here, we report that Hook proteins constitute a novel family of cytosolic coiled coil proteins that bind to organelles and to microtubules. The conserved NH2-terminal domains of Hook proteins mediate attachment to microtubules, whereas the more divergent COOH-terminal domains mediate the binding to organelles. Human Hook3 bound to Golgi membranes in vitro and was enriched in the cis-Golgi in vivo. Unlike other cis-Golgi–associated proteins, however, a large fraction of Hook3 maintained its juxtanuclear localization after Brefeldin A treatment, indicating a Golgi-independent mechanism for Hook3 localization. Because overexpression of Hook3 caused fragmentation of the Golgi complex, we propose that Hook3 participates in defining the architecture and localization of the mammalian Golgi complex.
Computerized recruiting for clinical trials in real time.

STUDY OBJECTIVE Success of prospective studies, particularly in the emergency department, often depends on immediate identification of eligible patients to ensure timely sample collection and initiation of study interventions. We report use of a real-time automated notification system to identify potential patients for a clinical trial at the time of ED registration on the basis of information routinely collected. We hypothesize that the automated notification system improves the rate of investigator notification. METHODS We performed a prospective comparison of the notification rate by the automated notification system compared with that by ED clinicians. RESULTS In the 11 months before use of the automated notification system, the investigator was notified by ED staff for 56% of 61 potentially eligible patients. During 10 months of using the automated notification system, the investigator was paged by the automated notification system for 84% of 49 potentially eligible patients. CONCLUSION The automated notification system improves study investigator notification. Use requires online linked registration, a database, and paging systems. The automated notification system is a potentially valuable tool in the recruitment of patients for clinical trials.
Molecularly Targeted Agents as Radiosensitizers in Cancer Therapy—Focus on Prostate Cancer

As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in the treatment of various malignancies with a prominent role in the care of prostate cancer patients, and efforts to improve the therapeutic ratio of radiation by technologic and pharmacologic means have led to important advances in cancer care. One promising approach is to combine molecularly targeted systemic agents with radiotherapy to improve tumor response rates and likelihood of durable control. This review first explores the limitations of preclinical studies as well as barriers to successful implementation of clinical trials with radiosensitizers. Special considerations related to and recommendations for the design of preclinical studies and clinical trials involving molecularly targeted agents combined with radiotherapy are provided. We then apply these concepts by reviewing a representative set of targeted therapies that show promise as radiosensitizers in the treatment of prostate cancer.
Internal Distraction Resulted in Improved Patient-Reported Outcomes for Midface Hypoplasia

Background: Both internal and external distraction devices have been used successfully in correcting midface hypoplasia. Although the indication for surgery and the osteotomy techniques may be similar, deciding when to use internal versus external devices has not been studied. The authors studied patient-reported outcomes with FACE-Q and functional surveys for internal and external devices for midface distraction patients. Methods: Patients who underwent distraction advancement after Le Fort I and Le Fort III were surveyed using the FACE-Q survey and a functional survey. Equal groups of internal and external device patients were compared (n = 64). Data recorded included: sex, age, follow-up, diagnosis, operating room time, expected blood loss, length of stay, distraction length, consolidation time, and complications. Results: Internal and external device groups were similar with regards to patient diagnosis, operative time, expected blood loss, distraction length but consolidation times differed (internal = 3.6 versus external = 1.1 months). For FACE-Q appearance appraisal, there were similarities in domain and scale. For the functional survey (airway/breathing, ocular/vision, occlusion/eating, speech/articulation), there was also similar scoring. However, internal device patients had superior FACE-Q scores for Quality of Life: Social Function (80.9 versus 68.9), Early Life Impact (92.9 versus 62.4), Dental Anxiety (70.2 versus 48.3), Psychological Well-being (87.8 versus 68.6); and Decision Satisfaction (81.2 versus 56.9) and Outcome Satisfaction (91.0 versus 84.7). Conclusions: Internal and external midface distraction patients had similar patient-reported outcomes for appearance and functional improvement; however, internal device patients were more satisfied with their quality of life and their decision to undergo the procedure.
When seeing outweighs feeling: a role for prefrontal cortex in passive control of negative affect in blindsight

Affective neuroscience has been strongly influenced by the view that a ‘feeling’ is the perception of somatic changes and has consequently often neglected the neural mechanisms that underlie the integration of somatic and other information in affective experience. Here, we investigate affective processing by means of functional magnetic resonance imaging in nine cortically blind patients. In these patients, unilateral postgeniculate lesions prevent primary cortical visual processing in part of the visual field which, as a result, becomes subjectively blind. Residual subcortical processing of visual information, however, is assumed to occur in the entire visual field. As we have reported earlier, these patients show significant startle reflex potentiation when a threat-related visual stimulus is shown in their blind visual field. Critically, this was associated with an increase of brain activity in somatosensory-related areas, and an increase in experienced negative affect. Here, we investigated the patients’ response when the visual stimulus was shown in the sighted visual field, that is, when it was visible and cortically processed. Despite the fact that startle reflex potentiation was similar in the blind and sighted visual field, patients reported significantly less negative affect during stimulation of the sighted visual field. In other words, when the visual stimulus was visible and received full cortical processing, the patients’ phenomenal experience of affect did not closely reflect somatic changes. This decoupling of phenomenal affective experience and somatic changes was associated with an increase of activity in the left ventrolateral prefrontal cortex and a decrease of affect-related somatosensory activity. Moreover, patients who showed stronger left ventrolateral prefrontal cortex activity tended to show a stronger decrease of affect-related somatosensory activity. Our findings show that similar affective somatic changes can be associated with different phenomenal experiences of affect, depending on the depth of cortical processing. They are in line with a model in which the left ventrolateral prefrontal cortex is a relay station that integrates information about subcortically triggered somatic responses and information resulting from in-depth cortical stimulus processing. Tentatively, we suggest that the observed decoupling of somatic responses and experienced affect, and the reduction of negative phenomenal experience, can be explained by a left ventrolateral prefrontal cortex-mediated inhibition of affect-related somatosensory activity.