Miracle-dz/UniFAR-FTUs huggingface dataset:
Composite Tissue Allotransplantation Immunology

Composite tissue allotransplantation (CTA) is an option recently introduced for major reconstruction of tissue defects. Since announcements of successful hand, larynx, knee, muscle, nerve, abdominal wall and, most recently, partial face transplantation, CTA has become one of the techniques used by plastic and reconstructive surgeons [1]. Clinical success in CTA is the culmination of progress in two disparate surgical disciplines: replantation and organ transplantation, a close collaboration between plastic and transplant surgeons. This joining of reconstructive and transplant surgery forces the movement of hand and facial tissue allotransplantation into the clinical arena [2]. Translation to the clinical field has shown that CTA is a viable treatment option for those who have lost extremities and suffered large tissue defects [3-5]. As with other allografts, CTA can undergo immune-mediated rejection. When compared with solid organ transplants, composite tissue allografts are histologically heterogeneous, composed of different tissue types (e.g., skin, muscle, bone, bone marrow, lymph nodes, nerve, and tendon), and express different immunogenicity of transplanted elements [6]. Currently, the most important issue for routine application of CTA to clinical practice is the need for lifelong immunosuppression [7]. The immunosuppression medications used to prevent tissue rejection in CTA are the same as those used in tens of thousands of solid organ transplant recipients. The toxicity of chronic, nonspecific immunosuppression remains a major limitation to the widespread availability of CTA and is associated with opportunistic infections, nephrotoxicity, end-organ damage, and an increased rate of malignancy [6]. Because composite tissue allograft transplantations are not life-saving procedures, much attention has been devoted to the issue of minimizing or withdrawing immunosuppression, and this would represent a significant step forward in this field [8]. Over the past five to six decades, advances in the field of transplant immunology have transformed solid organ transplantation into standard care, with excellent short term results in kidney, heart, lung, liver, and pancreas transplantation. The science of CTA is rooted in progressive thinking and the innovative solutions of plastic surgeons. Development of a tolerance regimen or new less toxic immunosuppressive protocols is essential for future acceptance of CTA [9]. With cautious optimism and healthy critiques, the science of CTA promises a bright future. This paper reviews key terminology, drug combinations, mechanisms of immunosuppression, the risks associated with CTA, and immune tolerance protocols.
Author ' s response to reviews Title : RNA viruses in community-acquired childhood pneumonia in semi-urban Nepal ; a cross-sectional study

Maria Mathisen (maria.mathisen@cih.uib.no) Tor A Strand (tor.strand@cih.uib.no) Biswa N Sharma (biswasharma@hotmail.com) Ram K Chandyo (ram.chandyo@cih.uib.no) Palle Valentiner-Branth (PVB@ssi.dk) Sudha Basnet (sudhacbasnet@gmail.com) Ramesh K Adhikari (ramesh@healthnet.org.np) Dag Hvidsten (Dag.Hvidsten@unn.no) Prakash S Shrestha (shresthaps@hotmail.com) Halvor Sommerfelt (halvor.sommerfelt@cih.uib.no)
THink: Inferring Cognitive Status from Subtle Behaviors

The Digital Clock Drawing Test is a fielded application that provides a major advance over existing neuropsychological testing technology. It captures and analyzes high precision information about both outcome and process, opening up the possibility of detecting subtle cognitive impairment even when test results appear superficially normal. We describe the design and development of the test, document the role of AI in its capabilities, and report on its use over the past seven years. We outline its potential implications for earlier detection and treatment of neurological disorders. We also set the work in the larger context of the THink project, which is exploring multiple approaches to determining cognitive status through the detection and analysis of subtle behaviors.
A Dominant-Negative Approach That Prevents Diphthamide Formation Confers Resistance to Pseudomonas Exotoxin A and Diphtheria Toxin

Diphtheria toxin (DT), Pseudomonas aeruginosa Exotoxin A (ETA) and cholix toxin from Vibrio cholerae share the same mechanism of toxicity; these enzymes ADP-rybosylate elongation factor-2 (EF-2) on a modified histidine residue called diphthamide, leading to a block in protein synthesis. Mutant Chinese hamster ovary cells that are defective in the formation of diphthamide have no distinct phenotype except their resistance to DT and ETA. These observations led us to predict that a strategy that prevents the formation of diphthamide to confer DT and ETA resistance is likely to be safe. It is well documented that Dph1 and Dph2 are involved in the first biochemical step of diphthamide formation and that these two proteins interact with each other. We hypothesized that we could block diphthamide formation with a dominant negative mutant of either Dph1 or Dph2. We report in this study the first cellular-targeted strategy that protects against DT and ETA toxicity. We have generated Dph2(C-), a dominant-negative mutant of Dph2, that could block very efficiently the formation of diphthamide. Cells expressing Dph2(C-) were 1000-fold more resistant to DT than parental cells, and a similar protection against Pseudomonas exotoxin A was also obtained. The targeting of a cellular component with this approach should have a reduced risk of generating resistance as it is commonly seen with antibiotic treatments.
Different underlying mechanisms for deficits in concept formation in dementia.

We investigated the different mechanisms that may underlie deficits in verbal concept formation among patients with Alzheimer's disease (AD) and ischaemic vascular dementia (IVD) associated with periventricular and deep white matter alterations. Concept formation was assessed with the WAIS-R Similarities subtest (SIM). Two types of errors were re-coded from the 0-point responses as scored by the WAIS-R manual. In set errors (e.g., dog-lion "they're alive") were coded when patients reported a very vague superordinate concept for the word pair. Out of set responses (e.g., dog-lion "the lion roars and the dog barks") were coded when a response was clearly out of mental set, i.e., when participants were unable to provide a superordinate concept for the word pair. Between-group comparisons demonstrated no difference in SIM test performance according to the scoring system described in the WAIS-R manual. Nonetheless, AD patients produced a greater proportion of in set errors, while IVD patients produced a greater proportion of out of set errors. Out of set errors were highly associated with measures of executive function, while in set errors were associated with measures related to delayed recognition memory and semantic intrusion errors. We conclude that the underlying deficits that contribute to poor concept formation differ between AD and IVD patients. In IVD impaired concept formation is related to deficits in the executive systems necessary to monitor responses and sustain mental set. In AD, by contrast, the deficit appears to be secondary to impaired verbal response selection.
Patient satisfaction with in-centre haemodialysis care: an international survey

Objectives To evaluate patient experiences of specific aspects of haemodialysis care across several countries. Design Cross-sectional survey using the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) questionnaire. Setting Haemodialysis clinics within a single provider in Europe and South America. Participants 2748 adults treated in haemodialysis. Primary and secondary outcomes The primary outcome was patient satisfaction with overall care. Secondary outcomes included patient experiences of individual aspects of dialysis care. Results 2145 (78.1%) adults responded to the questionnaire. Fewer than half (46.5% (95% CI 44.5% to 48.6%)) rated their overall care as excellent. Global perceptions of care were uninfluenced by most respondent characteristics except age and depressive symptoms; older respondents were less critical of their care (adjusted OR for excellent rating 1.44 (1.01 to 2.04)) and those with depressive symptoms were less satisfied (0.56 (0.44 to 0.71)). Aspects of care that respondents most frequently ranked as excellent were staff attention to dialysis vascular access (54% (52% to 56%)); caring of nurses (53% (51% to 55%)); staff responsiveness to pain or discomfort (51% (49% to 53%)); caring, helpfulness and sensitivity of dialysis staff (50% (48% to 52%)); and ease of reaching dialysis staff by telephone (48% (46% to 50%)). The aspects of care least frequently ranked as excellent were information provided when choosing a dialysis modality (23% (21% to 25%)), ease of seeing a social worker (28% (24% to 32%)), information provided about dialysis (34% (32% to 36%)), accuracy of information from nephrologist (eg, about prognosis or likelihood of a kidney transplant; 37% (35% to 39%)) and accuracy of nephrologists’ instructions (39% (36% to 41%)). Conclusions Haemodialysis patients are least satisfied with the complex aspects of care. Patients’ expectations for accurate information, prognosis, the likelihood of kidney transplantation and their options when choosing dialysis treatment need to be considered when planning healthcare research and practices.
Optimizing the Series Connection of Thermal Converters for AC-DC Current Calibration - Experimental Verification

Connecting thermal current converters (TCC) in series for calibration of current ac-dc difference, attention has to be paid to the various current leakages that may occur. Calculations indicate leakage error less than 2*10-6 at frequencies up to 100 kHz. Measured values show that error contributions are less than 1*10-6 at 100 kHz, which is well below the predicted value
Studying Affect Among the Chinese: The Circular Way

Past research on Chinese emotion has been plagued by the lack of a measurement map for affective feelings. In this article, I developed a fine-grained circumplex model of affective feelings that is arbitrarily defined by 12 segments. I created twelve 4-item self-report scales to measure affect felt during a clearly remembered moment (N = 395), and I cross-validated them twice with affect felt during the current moment (Ns = 269, 302). The structural and psychometric properties of these scales were strongly supported. The CIRCUM-extension procedure (M. Browne, personal communication, June 12, 1999) that places external correlates into the affective space showed that 28 of 28 mood states and 6 of 13 traits were significantly related to affect. External correlates did not clarify which of the affect dimensions were basic. The newly developed scales will serve as a useful tool in assessing affect among Chinese people and as a platform on which to extend the nomological net of affect.
The Highly Conserved Codon following the Slippery Sequence Supports −1 Frameshift Efficiency at the HIV-1 Frameshift Site

HIV-1 utilises −1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication. A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating −1 frameshifting in HIV-1. The GGG glycine codon immediately following the slippery sequence (the ‘intercodon’) contributes structurally to the start of the stem-loop but has no defined role in current models of the frameshift mechanism, as slippage is inferred to occur before the intercodon has reached the ribosomal decoding site. This GGG codon is highly conserved in natural isolates of HIV. When the natural intercodon was replaced with a stop codon two different decoding molecules—eRF1 protein or a cognate suppressor tRNA—were able to access and decode the intercodon prior to −1 frameshifting. This implies significant slippage occurs when the intercodon is in the (perhaps distorted) ribosomal A site. We accommodate the influence of the intercodon in a model of frame maintenance versus frameshifting in HIV-1.
Identification of patients with high-risk lymph node-negative colorectal cancer and potential benefit from adjuvant chemotherapy.

BACKGROUND Adjuvant chemotherapy is not indicated in lymph node-negative colorectal adenocarcinoma (CRC), even though some cases will present recurrent disease. It is important to identify a subgroup of patients with the highest risk of relapse because of the potential benefit of adjuvant chemotherapy. The objective of this study is to define the prognostic factors and describe a method for the selection of this subgroup. METHODS A retrospective cohort of 124 patients with lymph node-negative CRC with complete surgical resection was studied. Cox's proportional hazards model was used to define the prognostic factors associated with CRC-related survival and to develop a method for prediction of recurrence probability. RESULTS The cohort included 62 women and 62 men with mean age 55.8 years. The mean follow-up period was 11.7 years. T classification of the primary tumor, differentiation grade, carcinoembryonic antigen level, gender and the presence of neural invasion were significant prognostic factors according to the multivariate analysis (final model P=0.00001). Using risk ratios for these prognostic factors, we defined a high-risk group of 78 patients and a low-risk group of 46 patients with 24 and 5 recurrences, respectively (recurrence rates of 30.8% and 10.9% respectively, P=0.011). CONCLUSIONS Using these factors, a prognostic scale was developed to predict high risk of recurrence in cases of completely resected CRC and to identify them as a subgroup of patients with potential benefit of adjuvant chemotherapy.
DMSO-Free Programmed Cryopreservation of Fully Dissociated and Adherent Human Induced Pluripotent Stem Cells

Three modes for cryopreservation (CP) of human iPSC cells have been compared: STD: standard CP of small clumps with 10% of CPA in cryovials, ACC: dissociation of the cells with Accutase and freezing in cryovials, and PLT: programmed freezing of adherent cells in plastic multiwell dishes in a programmable freezer using one- and multistep cooling protocols. Four CPAs were tesetd: dimethyl sulfoxide (DMSO), ethylene glycol (EG), propylene glycol (PG), and glycerol (GLY). The cells in ACC and PLT were frozen and recovered after thawing in the presence of a ROCK inhibitor Y-27632 (RI). EG was less toxic w/o CP cryopreservation than DMSO and allowed much better maintenance of pluripotency after CP than PG or GLY. The cells were cryopreserved very efficiently as adherent cultures (+RI) in plates (5-6-fold higher than STD) using EG and a 6-step freezing protocol. Recovery under these conditions is comparable or even higher than ACC+RI. Conclusions. Maintenance of cell-substratum adherence is a favorable environment that mitigates freezing and thawing stresses (ComfortFreeze® concept developed by CELLTRONIX). CP of cells directly in plates in ready-to-go after thawing format for HT/HC screening can be beneficial in many SC-related scientific and commercial applications such as drug discovery and toxicity tests.
The incidence of occult malignant diseases in patients with deep venous thrombosis of the pelvis and lower limb

In 318 patients (155 men, 163 women) with an average age of 58.8 years (range 16–97 years), a retrospective study was carried out to determine the incidence of occult malignancies in patients with deep venous thrombosis affecting the pelvis and lower limb, confirmed by phlebography or duplex ultrasonography. It was found that, overall, 7.5% of all patients had occult malignant diseases, the most common being bronchial carcinoma (16%), colonic and renal carcinomas (12% each), and prostatic and pancreatic carcinoma (8% each). Of the patients with occult malignancy, 88% were older than 55 years. This fact shows that acute phlebothromboses may be a paraneoplastic early syndrome more often than was previously thought, and that patients older than 50 should always be screened for the presence of a tumor.
Central and Peripheral Corneal Thickness Measurement in Normal and Keratoconic Eyes Using Three Corneal Pachymeters

Purpose: To assess the agreement among ultrasonic pachymetry, the Galilei dual Scheimpflug analyzer, and Orbscan II for central and peripheral (Galilei vs. Orbscan) corneal thickness (CCT and PCT) measurement in normal and keratoconic eyes. Methods: In this prospective study, CCT and PCT were measured in 88 eyes of 88 refractive surgery candidates and 128 eyes of 69 keratoconic patients with ultrasonic pachymetry, the Galilei, and Orbscan II. The readings by the three instruments were compared using one-way analysis of normal variance. Agreement among the three devices was assessed using Pearson and intraclass correlation coefficients, and Bland–Altman plots. The same analyses were employed to evaluate agreement between Galilei and Orbscan II for PCT measurement. Results: In the normal group, mean CCT was 551.0±39.4, 566.9±33.5, and 565.5±40.9 μm measured by ultrasonic pachymetry, the Galilei, and Orbscan II, respectively (P<0.001). The corresponding figures in the keratoconus group were 492.0±61.7, 502.0±42.1, and 470.6±56.9 μm, respectively (P<0.001). Mean PCT was 612.5±35.3 and 640.9±38.0 μm in the normal group (P<0.001) and 567.6±35.2 and 595.1±41.4 μm in the keratoconus group (P<0.001) by the Galilei and Orbscan II, respectively. CCT and PCT measurements obtained by different devices were significantly correlated in both groups. Conclusion: To measure CCT, the Galilei and Orbscan II can be used interchangeably in normal eyes, but not in keratoconic eyes. For PCT, there is a systematic error between measurements obtained by the Galilei and Orbscan II. However, it is possible to change optical pachymeter readings into those obtained by ultrasonic pachymetry using a constant.
Chloroquine Inhibits Paracoccidioides brasiliensis Survival within Human Monocytes by Limiting the Availability of Intracellular Iron

The mechanisms used by Paracoccidioides brasiliensis (Pb 18) to survive into monocytes are not clear. Cellular iron metabolism is of critical importance to the growth of several intracellular pathogens, including P. brasiliensis, whose capacity to multiply in mononuclear phagocytes is dependent on the availability of intracellular iron. Chloroquine, by virtue of its basic properties, has been shown to prevent release of iron from holotransferrin by raising endocytic and lysosomal pH, and thereby interfering with normal iron metabolism. Then, in view of this, we have studied the effects of CHLOR on P. brasiliensis multiplication in human monocytes and its effect on the murine paracoccidioidomycosis. CHLOR induced human monocytes to kill P. brasiliensis. The effect of CHLOR was reversed by FeNTA, an iron compound that is soluble at neutral to alkaline pH, but not by holotransferrin, which releases iron only in an acidic environment. CHLOR treatment of Pb 18‐infected BALB/c mice significantly reduced the viable fungi recovery from lungs, during three different periods of evaluation, in a dose‐dependent manner. This study demonstrates that iron is of critical importance to the survival of P. brasiliensis yeasts within human monocytes and the CHLOR treatment in vitro induces Pb 18 yeast‐killing by monocytes by restricting the availability of intracellular iron. Besides, the CHLOR treatment in vivo significantly reduces the number of organisms in the lungs of Pb‐infected mice protecting them from several infections. Thus, CHLOR was effective in the treatment of murine paracoccidioidomycosis, suggesting the potential use of this drug in patients' treatment.
Actions of Genistein on Cystic Fibrosis Transmembrane Conductance Regulator Channel Gating

Previous studies have shown that genistein increased cystic fibrosis transmembrane conductance regulator (CFTR) channel activity in the presence of saturating concentrations of forskolin and calyculin A in intact cells. Possible molecular mechanisms for genistein's action include inhibition of tyrosine kinases, inhibition of serine/threonine protein phosphatases, or direct binding of genistein to CFTR. Since genistein inhibits several enzymes that hydrolyze ATP, and ATP hydrolysis is an intrinsic property of CFTR, we examined the effect of genistein on CFTR gating in excised inside-out patches from Hi-5 insect cells and NIH3T3 cells expressing recombinant CFTR. Genistein (50 μM) did not open phosphorylated CFTR channels by itself, but increased the ATP- induced CFTR channel current by approximately twofold. A similar magnitude of enhancement was observed when genistein was applied with PKI, a specific inhibitor of protein kinase A, or vanadate, a tyrosine phosphatase inhibitor, suggesting that inhibition of protein phosphatases or tyrosine kinases does not account for genistein's effects. The enhancement of channel current increased with increasing concentrations of genistein and reached a maximum at 35 μM genistein. At higher concentrations of genistein concentration, CFTR channel current decreased, resulting in a bell-shaped dose–response relationship. In the absence of genistein, both open- and closed-time histograms could be fitted with a single exponential function, yielding a mean open time (τO) of 0.302 ± 0.002 s, and a mean closed time (τC) of 0.406 ± 0.003 s. In the presence of 50 μM genistein, the open time histogram could be fitted with a double exponential function with τO1 = 0.429 ± 0.003 s and τO2 = 2.033 ± 0.173 s. Thus, genistein induced a prolonged open state, an effect that mimics that of nonhydrolyzable ATP analogs. Closed time analysis showed that 50 μM genistein caused a prolonged closed state with a time constant of 2.410 ± 0.035 s. We thus conclude that (a) the effects of genistein are likely caused by a direct binding of the drug to the CFTR protein, and (b) at least two binding sites are required to explain the effects of genistein: a high affinity site that decreases the closing rate and a low affinity site that reduces the opening rate.
Experience with videoconferencing between a neonatal unit and the families' home from the perspective of certified paediatric nurses

Parents of preterm-born infants need support after returning to their homes with their baby. We studied the experience of certified paediatric nurses (CPNs) with the use of videoconferencing between the neonatal intensive care unit and the families' home. Families were given a home videoconferencing unit, which allowed them to contact staff at the neonatal unit, day and night. Over a period of 12 months, ten families used the videoconferencing equipment. Families made a median of 4 telemedicine calls each (range 2–30). Narrative interviews were performed with 10 CPNs after the study ended. Qualitative thematic content analysis was applied to the interview data and one theme was identified: smoothing the transition of infants from the neonatal unit to the families' home. The CPNs found that videoconferencing helped them to assess the overall situation at home and facilitated the relationship between parents and the infant. The CPNs felt that they were able to provide security to the family. The use of videoconferencing was considered as a generally positive experience and as a tool to improve nursing care at home.