Miracle-dz/UniFAR-FTUs huggingface dataset:
Plain and pain talk in palliative and hospice care: multidirectional knowledge transfer and shared decision making.

Since the beginning of time, the patient and physician have been the main actors in managing acute and chronic medical care decisions. The evolving concepts of palliative and hospice care, however, have expanded the number of professionals who have influential roles in implementing the goals and expectations onbehalf of the patient. The traditional patientYphysician dyad has its origins in the ethical principles of benevolence, where ‘‘the doctorYpatient relationship is characterized by power/knowledge inequalities and has been dominated by paternalism in Western societies. ’’ More recently, the concept of the interprofessional team healthcare delivery model as promulgated by the Institute of Medicine’s pivotal 2003 report, ‘‘Health Professions Education: A Bridge to Quality,’’ called for students and working professionals to develop and maintain 5 core competencies, including ‘‘working in interdisciplinary teams and engaging in quality improvement principles. ’’ This month’s continuing education activity (page 130) expands the dyad to a ‘‘circle of care,’’ which includes many factors or points of influence focused on the patient’s role in the management of his/her care. The goal of pain andpalliative care is tomaintain or improve the patient’s dignity and quality of life in general and, in particular, as it relates to the amelioration of acute and chronic pain in the context of wound care.
The Neddylation-Cullin 2-RBX1 E3 Ligase Axis Targets Tumor Suppressor RhoB for Degradation in Liver Cancer*

The neddylation-cullin-RING E3 ligase (CRL) pathway has recently been identified as a potential oncogenic event and attractive anticancer target; however, its underlying mechanisms have not been well elucidated. In this study, RhoB, a well known tumor suppressor, was identified and validated with an iTRAQ-based quantitative proteomic approach as a new target of this pathway in liver cancer cells. Specifically, cullin 2-RBX1 E3 ligase, which requires NEDD8 conjugation for its activation, interacted with RhoB and promoted its ubiquitination and degradation. In human liver cancer tissues, the neddylation-CRL pathway was overactivated and reversely correlated with RhoB levels. Moreover, RhoB accumulation upon inhibition of the neddylation-CRL pathway for anticancer therapy contributed to the induction of tumor suppressors p21 and p27, apoptosis, and growth suppression. Our findings highlight the degradation of RhoB via the neddylation-CRL pathway as an important molecular event that drives liver carcinogenesis and RhoB itself as a pivotal effector for anticancer therapy targeting this oncogenic pathway.
Clinical Evaluation of Wound Healing in Split-Skin Graft Donor Sites Using Microscopic Quantification of Reepithelialization

OBJECTIVE:Impaired or delayed wound healing is a common health problem. However, it remains challenging to predict whether wounds in patients will heal without complication or will have a prolonged healing time. In this study, the authors developed an objective screening tool to assess wound healing using microscopic quantification of reepithelialization in a split-thickness skin graft wound model and used this tool to identify risk factors for defective wound healing. DESIGN:Thirty patients (16 male and 14 female) were included in this prospective study. Anterior thigh skin biopsies from the donor site region of partial-thickness skin grafts were dressed with moisture-retentive dressings, and biopsies were examined on days 0, 2, 5, and 10 postoperatively by microscopy. Images were then transferred to a computer for image analysis and epithelial measurements (epithelial thickness and total reepithelialized surface). The effects of gender, age, body mass index, and smoking behavior on these wound healing parameters were determined. RESULTS:The authors found comparable results for the computer and traditional measure methods. However, the time required to perform the measurements using the semiautomated computer method was less than half the time of the traditional method. Image capturing, enhancing, and analysis with the new method required approximately 2 minutes 30 seconds, whereas the traditional methods took up to 7 minutes per image. The total size of the reepithelialized surface (P = .047) and percentage of the biopsy resurfaced with epithelia (P = .011) at day 10 were both significantly higher in male patients compared with female patients. In patients younger than 55 years, reepithelialized areas were significantly thicker than in patients older than 55 years (P = .008), whereas the size of the reepithelialized surface showed no differences. No significant differences in reepithelialization parameters were found concerning body mass index and smoking behavior. CONCLUSIONS:Both male gender and older age impair reepithelialization rate and epithelial thickness in partial-thickness skin graft donor site wounds. In contrast, body mass index and smoking behavior have not been shown to be influencing factors on reepithelialization. Thus, microscopic quantification of reepithelialization might be a suitable method for predicting complications associated with wound healing.
Population genomic analysis of Tunisian Medicago truncatula reveals candidates for local adaptation.

Genome-wide association studies rely upon segregating natural genetic variation, particularly the patterns of polymorphism and correlation between adjacent markers. To facilitate association studies in the model legume Medicago truncatula, we present a genome-scale polymorphism scan using existing Affymetrix microarrays. We develop and validate a method that uses a simple information-criteria algorithm to call polymorphism from microarray data without reliance on a reference genotype. We genotype 12 inbred M. truncatula lines sampled from four wild Tunisian populations and find polymorphisms at approximately 7% of features, comprising 31 419 probes. Only approximately 3% of these markers assort by population, and of these only 10% differentiate between populations from saline and non-saline sites. Fifty-two differentiated probes with unique genome locations correspond to 18 distinct genome regions. Sanger resequencing was used to characterize a subset of maker loci and develop a single nucleotide polymorphism (SNP)-typing assay that confirmed marker assortment by habitat in an independent sample of 33 individuals from the four populations. Genome-wide linkage disequilibrium (LD) extends on average for approximately 10 kb, falling to background levels by approximately 500 kb. A similar range of LD decay was observed in the 18 genome regions that assort by habitat; these LD blocks delimit candidate genes for local adaptation, many of which encode proteins with predicted functions in abiotic stress tolerance and are targets for functional genomic studies. Tunisian M. truncatula populations contain substantial amounts of genetic variation that is structured in relatively small LD blocks, suggesting a history of migration and recombination. These populations provide a strong resource for genome-wide association studies.
STUDIES OF THE ETIOLOGY OF THE COMMON COLD

In recent years widespread recognition has come about of the fact that the common cold is not a simple minor infection of the upper respiratory tract which, because of its mild symptomatology, can be conveniently disregarded. The more thorough study of this disease begins to indicate that perhaps it may be the keystone of that complex structure of ills the etiologic agents of which gain entrance to the body by way of the upper respiratory tract. A complete understanding of the pathogenesis of the common cold would not only be of value in solving the nature of this malady itself but would undoubtedly throw important light on the mechanism of all respiratory infection and even perhaps on certain diseases that are not regarded as clearly respiratory in origin. Information concerning the etiology of the common cold is obviously the sine qua non of the understanding of this infection and of
Complications Associated With Retained Implants After Plate Fixation of the Pediatric Forearm

Objective: Our present study examines the complications of pediatric patients treated with plate fixation for forearm fractures. Design: Case series of pediatric patients after their forearm fracture was fixed using a plate, with the majority of patients retaining their implants. Setting: Level 1 Trauma Center. Methods: From 1999 to 2009, 58 patients between the ages of 6 and 15 years had fixation of their forearm fracture with plates. Thirty-three of these patients were available for a long-term follow-up with an average of 6.4 years. The patients were interviewed over the phone, and a physician filled out a questionnaire with regard to their clinical course. Records and x-ray data were reviewed for each patient. Factors such as implant complications, functional activity level, pain score, and clinical symptoms were studied. Results: Fractures occurred in 7.1% (2/28) of the patients who chose to retain their implants. Of the 28 patients who initially chose to leave the implants in place, 17.9% (5/28) had a partial or complete removal of the implants because of irritation. These patients reported the following symptoms: mild pain 42.3% (11/26), clicking 34.6% (9/26), ability to feel the plates 73.1% (19/26), and mild weakness 26.9% (7/26). The number of patients who reported return to the preinjury level of activity was 88.5% (23/26), and 96.2% (25/26) reported being satisfied with their clinical outcome when implants were retained. Females had a significantly greater subjective weakness of 60.0% (6/10) compared with that of males, which was 14.3% (3/21; P = 0.009) after a forearm fracture. The inability to return to the preinjury level of activity was significantly greater for females, which was 30.0% (3/10) versus 0.0% (0/21) for males (P = 0.008). Conclusions: We concluded that retaining the plates in pediatric forearm fractures does not increase the refracture rate compared with the removal from the historical rates in the literature. Patients should be warned of possible symptoms and complications that may be present with retained plates. Also, a more aggressive physical therapy may be considered for females because they were observed to have more subjective weakness and dysfunction at long-term follow-up. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Impact of Cystinosin Glycosylation on Protein Stability by Differential Dynamic Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)*

Cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by intralysosomal accumulation of cystine. The causative gene for cystinosis is CTNS, which encodes the protein cystinosin, a lysosomal proton-driven cystine transporter. Over 100 mutations have been reported, leading to varying disease severity, often in correlation with residual cystinosin activity as a transporter and with maintenance of its protein-protein interactions. In this study, we focus on the ΔITILELP mutation, the only mutation reported that sometimes leads to severe forms, inconsistent with its residual transported activity. ΔITILELP is a deletion that eliminates a consensus site on N66, one of the protein's seven glycosylation sites. Our hypothesis was that the ΔITILELP mutant is less stable and undergoes faster degradation. Our dynamic stable isotope labeling by amino acids in cell culture (SILAC) study clearly showed that wild-type cystinosin is very stable, whereas ΔITILELP is degraded three times more rapidly. Additional lysosome inhibition experiments confirmed ΔITILELP instability and showed that the degradation was mainly lysosomal. We observed that in the lysosome, ΔITILELP is still capable of interacting with the V-ATPase complex and some members of the mTOR pathway, similar to the wild-type protein. Intriguingly, our interactomic and immunofluorescence studies showed that ΔITILELP is partially retained at the endoplasmic reticulum (ER). We proposed that the ΔITILELP mutation causes protein misfolding, ER retention and inability to be processed in the Golgi apparatus, and we demonstrated that ΔITILELP carries high-mannose glycans on all six of its remaining glycosylation sites. We found that the high turnover of ΔITILELP, because of its immature glycosylation state in combination with low transport activity, might be responsible for the phenotype observed in some patients.
Rootless with undetectable meristem 1 encodes a monocot-specific AUX/IAA protein that controls embryonic seminal and post-embryonic lateral root initiation in maize.

The maize (Zea mays L.) rum1-R (rootless with undetectable meristems 1-Reference) mutant does not initiate embryonic seminal roots and post-embryonic lateral roots at the primary root. Map-based cloning revealed that Rum1 encodes a 269 amino acid (aa) monocot-specific Aux/IAA protein. The rum1-R protein lacks 26 amino acids including the GWPPV degron sequence in domain II and part of the bipartite NLS (nuclear localization sequence). Significantly reduced lateral root density (approximately 35%) in heterozygous plants suggests that the rum1-R is a semi-dominant mutant. Overexpression of rum1-R under the control of the maize MSY (Methionine SYnthase) promoter supports this notion by displaying a reduced number of lateral roots (31-37%). Functional characterization suggests that Rum1 is auxin-inducible and encodes a protein that localizes to the nucleus. Moreover, RUM1 is unstable with a half life time of approximately 22 min while the mutant rum1-R protein is very stable. In vitro and in vivo experiments demonstrated an interaction of RUM1 with ZmARF25 and ZmARF34 (Z. mays AUXIN RESPONSE FACTOR 25 and 34). In summary, the presented data suggest that Rum1 encodes a canonical Aux/IAA protein that is required for the initiation of embryonic seminal and post-embryonic lateral root initiation in primary roots of maize.
Ehd3, encoding a plant homeodomain finger-containing protein, is a critical promoter of rice flowering.

Oryza sativa (rice) flowers in response to photoperiod, and is a facultative short-day (SD) plant. Under SD conditions, flowering is promoted through the activation of FT-like genes (rice florigens) by Heading date 1 (Hd1, a rice CONSTANS homolog) and Early heading date 1 (Ehd1, with no ortholog in the Arabidopsis genome). On the other hand, under long-day (LD) conditions, flowering is delayed by the repressive function of Hd1 on FT-like genes and by downregulation of Ehd1 by the flowering repressor Ghd7 - a unique pathway in rice. We report here that an early heading date 3 (ehd3) mutant flowered later than wild-type plants, particularly under LD conditions, regardless of the Hd1-deficient background. Map-based cloning revealed that Ehd3 encodes a nuclear protein that contains a putative transcriptional regulator with two plant homeodomain (PHD) finger motifs. To identify the role of Ehd3 within the gene regulatory network for rice flowering, we compared the transcript levels of genes related to rice flowering in wild-type plants and ehd3 mutants. Increased transcription of Ghd7 under LD conditions and reduced transcription of downstream Ehd1 and FT-like genes in the ehd3 mutants suggested that Ehd3 normally functions as an LD downregulator of Ghd7 in floral induction. Furthermore, Ehd3 ghd7 plants flowered earlier and show higher Ehd1 transcript levels than ehd3 ghd7 plants, suggesting a Ghd7-independent role of Ehd3 in the upregulation of Ehd1. Our results demonstrate that the PHD-finger gene Ehd3 acts as a promoter in the unique genetic pathway responsible for photoperiodic flowering in rice.
Deep Coverage Mouse Red Blood Cell Proteome

Mice have close genetic/physiological relationships to humans, breed rapidly, and can be genetically modified, making them the most used mammal in biomedical research. Because the red blood cell (RBC) is the sole gas transporter in vertebrates, diseases of the RBC are frequently severe; much research has therefore focused on RBC and cardiovascular disorders of mouse and humans. RBCs also host malaria parasites. Recently we presented an in-depth proteome for the human RBC. Here we present directly comparable data for the mouse RBC as membrane-only, soluble-only, and combined membrane-bound/soluble proteomes (comprising, respectively, 247, 232, and 165 proteins). All proteins were identified, validated, and categorized in terms of subcellular localization, protein family, and function, and in comparison with the human RBC, were classified as orthologs, family-related, or unique. Splice isoforms were identified, and polypeptides migrating with anomalous apparent molecular weights were grouped into putatively ubiquitinated or partially degraded complexes. Overall there was close concordance between mouse and human proteomes, confirming the unexpected RBC complexity. Several novel findings in the human proteome have been confirmed here. This comparison sheds light on several open issues in RBC biology and provides a departure point for more comprehensive understanding of RBC function.
Unrestrictive Identification of Multiple Post-translational Modifications from Tandem Mass Spectrometry Using an Error-tolerant Algorithm Based on an Extended Sequence Tag Approach*S

Identification of post-translational modifications (PTMs) is important to understanding the biological functions of proteins. MS/MS is a useful tool to identify PTMs. Most existing search tools are restricted to take only a few types of PTMs as input. Here we describe a new algorithm, called MODi (pronounced “mod eye”), that rapidly searches for all known types of PTMs at once without limiting a multitude of modified sites in a peptide. MODi introduces the notion of a tag chain, a combination structure made from multiple sequence tags, that effectively localizes modified regions within a spectrum and overcomes de novo sequencing errors common in tag-based approaches. MODi showed its performance competence by identifying various types of PTMs in analysis of PTM-rich proteins such as glyceraldehyde-3-phosphate dehydrogenase and lens protein. We demonstrated that MODi innovatively manages the computational complexity of identifying multiple PTMs in a peptide, which may exist in a greater variety than usually expected. In addition, it is suggested that MODi has great potential to discover novel modifications.
Troponin level in patients with myopathies.

To the Editor: Measurement of troponin levels have been used in the diagnosis in patients with acute myocardial infarct (MI). The troponin complex is a group of proteins present in striate muscle and myocardium. The complex consists of 3 subunits TnT, located in actin filaments, TnI that affects myosinactin interactions, and TnC that binds divalent calcium ions. These subunits can be separated by immunologic techniques. The myocardium contains troponin T (CTnT) and I (CTnI) isoforms, but not troponin C. CTnI and CTnT are used in the diagnosing of acute myocardial infarction as their elevation are more sensitive than the CKMB. We studied 25 patients with primary myopathies and elevated CK. Troponin levels were ordered without specifying the type. Patients included 8 with muscular dystrophy, 10 with polymyositis, and 4 with rhabdomyolysis. Eighteen patients had measurements of CTnT and 15 had measurements of CTnI. Both isoforms were measured in 8. CTnT was elevated in 50% of the patients that had this isoform measured, but CTnI was elevated in only 2 of the 15 (13%) in which this was measured. Of those that had both isoform measured, CTnT was elevated in 4, but none had TnI elevation. Of the 4 patients with rhabdomyolysis, 2 had CTnI measured, and it was elevated in one. Two patients had CTnI measured, and this was elevated in both correlating with elevated CK levels. Although both CTnT and CTnI are elevated in muscle damage, the raise of CTnI has been reported to be more specific and sensitive for myocardial damage, but the choice of which isoform is measured depends on the cost, rather than their specificity. Our findings indicate that both CTnT and CTnI, particularly CTnT, can be elevated in patients with myopathies without acute MI. Thus, we also concluded that cardiac troponin I is more specific to detect myocardial injury in myopathies. We cannot rule out that some patients, particularly those with rhabdomyolysis, had acute myocardial damage causing CTnI elevation. Our data should be taken into consideration in an acute setting in patients with myopathies and elevated CK, as elevated troponin levels might not necessarily indicate an acute MI. When ordering troponin levels for the diagnosis of MI, particularly in patients with myopathies, CTnI should be used.
Interplay between calcium signalling and early signalling elements during defence responses to microbe- or damage-associated molecular patterns.

While diverse microbe- or damage-associated molecular patterns (MAMPs/DAMPs) typically trigger a common set of intracellular signalling events, comparative analysis between the MAMPs flg22 and elf18 revealed MAMP-specific differences in Ca(2+) signalling, defence gene expression and MAMP-mediated growth arrest in Arabidopsis thaliana. Such MAMP-specific differences are, in part, controlled by BAK1, a kinase associated with several receptors. Whereas defence gene expression and growth inhibition mediated by flg22 were reduced in bak1 mutants, BAK1 had no or minor effects on the same responses elicited by elf18. As the residual Ca(2+) elevations induced by diverse MAMPs/DAMPs (flg22, elf18 and Pep1) were virtually identical in bak1 mutants, a differential BAK1-mediated signal amplification to attain MAMP/DAMP-specific Ca(2+) amplitudes in wild-type plants may be hypothesized. Furthermore, abrogation of reactive oxygen species (ROS) accumulation, either in the rbohD mutant or through inhibitor application, led to loss of a second Ca(2+) peak, demonstrating a feedback effect of ROS on Ca(2+) signalling. Conversely, mpk3 mutants showed a prolonged accumulation of ROS but this did not significantly impinge on the overall Ca(2+) response. Thus, fine-tuning of MAMP/DAMP responses involves interplay between diverse signalling elements functioning both up- or downstream of Ca(2+) signalling.