Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationship of interfacial equilibria to interfacial activation of phospholipase A2.

The equilibrium dissociation constants for the distribution of pig pancreatic phospholipase A2, its competitive inhibitors, and their complexes at the interface of a neutral diluent are determined. The relationship between these parameters and their significance for interfacial catalysis is elaborated in terms of a model based on the relationship between the underlying equilibria. By using a combination of spectroscopic and chemical modification methods, it was possible to determine the equilibrium dissociation constant of an inhibitor bound to the interface (K') or of the inhibitor bound to the enzyme in the aqueous phase (KI) or the interface (KI*). The equilibrium dissociation constant for the free enzyme (Kd) or for the enzyme-inhibitor complex (KdI) from the interface were also obtained. These constants are shown to be thermodynamically related, i.e., K'KdKI* = KIKdI, as predicted on the basis of the cyclic equilibrium scheme (thermodynamic box) describing the distribution of the enzyme and the inhibitor between the aqueous phase and the interface at constant calcium concentration. Results show that (i) calcium is required for the binding of a substrate or inhibitor molecule to the catalytic site; (ii) the effective dissociation constant of the inhibitor-enzyme complex in the aqueous phase is considerably larger than that for the enzyme at the interface, i.e., KI >> effective KI*; (iii) KdI does not depend on the structure of the inhibitor and Kd >> KdI; and (iv) structure-activity correlations suggest that ionic interactions between a ligand and the interfacial recognition site of the enzyme are important for K', which controls the concentration of the bound inhibitor that the enzyme "sees" in the interface. These observations demonstrate that the binding of the enzyme to the interface and the binding of the inhibitor to the active site of the enzyme at the interface are two distinguishable processes. Therefore, binding of a ligand to the active site of the enzyme promotes binding of the enzyme-inhibitor complex to other amphiphiles and the interface with higher affinity. It is suggested that the primary effect of binding the enzyme to the interface is to increase its intrinsic affinity toward the active-site-directed ligands, i.e., the interfacial activation of PLA2 is of K-type.
The effect of panel membership and feedback on ratings in a two-round Delphi survey: results of a randomized controlled trial.

BACKGROUND Past observational studies of the RAND/UCLA Appropriateness Method have shown that the composition of panels affects the ratings that are obtained. Panels of mixed physicians make different judgments from panels of single specialty physicians, and physicians who use a procedure are more likely to rate it more highly than those who do not. OBJECTIVES To determine the effect of using physicians and health care managers within a panel designed to assess quality indicators for primary care and to test the effect of different types of feedback within the panel process. METHOD A two-round postal Delphi survey of health care managers and family physicians rated 240 potential indicators of quality of primary care in the United Kingdom to determine their face validity. Following round one, equal numbers of managers and physicians were randomly allocated to receive either collective (whole sample) or group-only (own professional group only) feedback, thus, creating four subgroups of two single-specialty panels and two mixed panels. RESULTS Overall, managers rated the indicators significantly higher than physicians. Second-round scores were moderated by the type of feedback received with those receiving collective feedback influenced by the other professional group. CONCLUSIONS This paper provides further experimental evidence that consensus panel judgments are influenced both by panel composition and by the type of feedback which is given to participants during the panel process. Careful attention must be given to the methods used to conduct consensus panel studies, and methods need to be described in detail when such studies are reported.
Post‐Transplant Lymphoproliferative Disorders Following Liver Transplantation: Incidence, Risk Factors and Survival

This study investigates retrospectively the incidence, risk factors and mortality of post‐transplant lymphoproliferative disorders (PTLD) in adult orthotopic liver transplant (OLT) recipients. Among 1206 OLT recipients at a single institution, 37 developed a PTLD. The incidence of PTLD was highest during the first 18 months and relatively constant thereafter with cumulative incidence of 1.1% at 18 months and 4.7% at 15 years. The risk of PTLD was approximately 10% to 15% of the risk of death without PTLD. During the first 4 years following OLT, PTLD were predominantly related to EBV, while afterward most PTLD were EBV negative. Significant risk factors for PTLD in OLT recipients were transplantation for acute fulminant hepatitis during the first 18 months following OLT (HR = 2.6, p = 0.007), and rejection therapy with high‐dose steroids (HR = 4.5, p = 0.049) and OKT3 (HR = 3.9, p = 0.016) during the previous year. Therapy with high‐dose steroids or OKT3 (HR = 3.6, p = 0.0071) were also significant risk factors for PTLD‐associated mortality. OLT recipients remain at risk for PTLD years after transplantation. The strong association of PTLD with rejection therapy and the worse post‐PTLD prognosis among recipients of rejection therapy indicate the need to balance the risk of immunosuppression against the risk of PTLD following rejection treatment.
End-stage coxarthrosis and gonarthrosis. Aetiology, clinical patterns and radiological features of idiopathic osteoarthritis.

OBJECTIVES To determine and compare the aetiological background, clinical patterns and radiological features of idiopathic osteoarthritis (OA) of the hip and the knee warranting arthroplasty. METHODS A total of 402 Caucasians consecutively undergoing total hip replacement (THR) or total knee replacement (TKR) for idiopathic OA at a major centre was surveyed. RESULTS Previous joint injury was more common in the TKR group (P < 0.0001). However, both groups manifested a mixed occupational background, body mass indices similar to the general population and a predominance of females (F:M = 1.3-1.4:1). The TKR group had a significantly younger age of symptom onset (56 yr) than the THR group (61 yr) but both groups had a tendency to bilateral arthroplasty (33%), nodal involvement (54-59%), a significant excess of right-sided replacements (1.8:1, THR; 2.2:1, TKR) and similar levels of pre-operative pain and disability. Up to 40% of hips manifested acetabular dysplasia and 10% possible previous slipped upper femoral epiphyses. Eighty-five per cent with end-stage coxarthrosis or gonarthrosis had an identical pattern of radiographic disease contralaterally. CONCLUSIONS Our data suggest the importance of a constitutional tendency to idiopathic, end-stage OA, a disorder traditionally associated with environmental factors leading to 'wear and tear'.
SNARE protein expression in synaptic terminals and astrocytes in the adult hippocampus: A comparative analysis

Several evidences suggest that astrocytes release small transmitter molecules, peptides, and protein factors via regulated exocytosis, implying that they function as specialized neurosecretory cells. However, very little is known about the molecular and functional properties of regulated secretion in astrocytes in the adult brain. Establishing these properties is central to the understanding of the communication mode(s) of these cells and their role(s) in the control of synaptic functions and of cerebral blood flow. In this study, we have set‐up a high‐resolution confocal microscopy approach to distinguish protein expression in astrocytic structures and neighboring synaptic terminals in adult brain tissue. This approach was applied to investigate the expression pattern of core SNARE proteins for vesicle fusion in the dentate gyrus and CA1 regions of the mouse hippocampus. Our comparative analysis shows that astrocytes abundantly express, in their cell body and main processes, all three protein partners necessary to form an operational SNARE complex but not in the same isoforms expressed in neighbouring synaptic terminals. Thus, SNAP25 and VAMP2 are absent from astrocytic processes and typically concentrated in terminals, while SNAP23 and VAMP3 have the opposite expression pattern. Syntaxin 1 is present in both synaptic terminals and astrocytes. These data support the view that astrocytes in the adult hippocampus can communicate via regulated exocytosis and also indicates that astrocytic exocytosis may differ in its properties from action potential‐dependent exocytosis at neuronal synapses, as it relies on a distinctive set of SNARE proteins. © 2011 Wiley‐Liss, Inc.
The Impact of Benchmark Choice on US Mutual Fund Benchmark-Adjusted Performance and Ranking

This study re-visits the question of benchmark mismatch among 1281 US equity mutual funds and its impact on benchmark-adjusted fund performance and ranking. All funds report S&P500 index as a prospectus benchmark, yet 2/3 of those are placed in the Morningstar category with risk and objectives different to those of the S&P500 index. We identify ‘true’ benchmarks for those mismatched funds and find that their S&P adjusted alphas are higher than ‘true’ benchmark adjusted alphas in 61.2% of the cases. In terms of fund quartile rankings, 30% of winner funds lose that status when the prospectus benchmark is substituted with a more suited one. In the remaining performance quartiles there is no clear advantage of using S&P 500 as a prospectus benchmark. The prospectus benchmark therefore can mislead investors about fund’s relative performance. This leads us to conclude that any reference to performance in a fund’s prospectus should be treated with caution.
A lost generation? Racialization and stalled social mobility in a group of Roma migrants in the UK

The paper applies the notion of segmented assimilation to an inter-generational divide within a community of Roma migrants from Romania who settled in Manchester, UK. Drawing on long-term observations, we show how a successful trajectory of upward social mobility comes to a stall as the interplay between Roma-specific demographics (large families and traditional kin networks) and racialized policies sets a ‘mobility trap’, creating a ‘lost generation’ of young people who are unable to progress beyond the status of low-wage, vulnerable employee.
Risk Factors to Develop Ocular Surface Disease in Treated Glaucoma or Ocular Hypertension Patients

Purpose To identify risk factors for developing ocular surface disease (OSD), to verify the prevalence of OSD, and to record efficacy of questionnaires in identifying symptoms' impact on patients' quality of life. Methods This was an observational, cross-sectional study of patients with topically treated glaucoma. Tear film break-up time (TFBUT) and punctate keratitis were evaluated; 2 quality-of-life questionnaires (National Eye Institute–Visual Function Questionnaire 25 and Glaucoma Symptom Scale) were submitted to all patients. Class of previous and current intraocular pressure (IOP)–lowering drugs, number of drugs, number of drops/day, and total and current benzalkonium chloride (BAK) exposure were collected. Results A total of 233 patients completed the study. TFBUT was abnormal in 71 (30.5%) eyes; punctate keratitis was present in 74 (31.7%). Keratitis was more frequent with increasing number of eyedrops (p=0.008) and number of instillations per day (p=0.009). Ocular surface disease was present in 97 (41.6%) patients and was statistically related to number of medications used (p=0.026). The univariate analysis pointed out that patients with OSD were older (p=0.04), had lower IOP values (p=0.03), were topically treated for more time (p<0.0001), had assumed more BAK (p<0.0001), and presented worst quality of life (p<0.01). The multivariate analysis found that OSD was related to number of medications used (p=0.002), prolonged use of preserved medications (p=0.005), and total BAK exposure (p<0.001). Conclusions There is clinical evidence that the number of medications, their prolonged use, and the total BAK exposure are risk factors to develop OSD in patients with glaucoma. To prevent OSD onset, BAK exposure and the number of topical medications should be reduced.
Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect

Significance Xeroderma pigmentosum (XP) is a genetic disorder caused by defective repair of DNA damage. Affected patients are mutated in one of eight genes and develop skin pigmentation changes, skin cancers, ocular surface abnormalities, and, in some cases, acute sunburn and neurodegeneration. The XP proteins are involved in different steps in the repair of DNA damage. Examination of 89 patients, the largest reported cohort under long-term follow-up, by the same multidisciplinary team of clinicians and scientists has revealed unexpected clinical heterogeneity dependent on the affected gene and the exact mutation. Our findings provide new insights into the mechanisms of carcinogenesis, ocular surface disease, and neurodegeneration, as well as providing improved clinical management and more definitive prognostic predictions. Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins.
Myofilament remodeling during the progression of heart failure.

BACKGROUND Myocardial failure is associated with complex, pleiotropic responses involving multiple signaling mechanisms and alterations in structure-function relationships. Myofilament proteins are a central component of these responses and may be modified in various ways, including isoform variation, phosphorylation, and degradation. METHODS AND RESULTS We have modeled the transition from compensated hypertrophy to failure using a combination of isolated heart and in vitro motility methods in the Dahl salt sensitive rat model. CONCLUSIONS Our results and prior data indicate that myosin isoform switching probably does not have major functional consequences in failing human myocardium. In contrast, a defect in the thin filament appears to play an important role in the Dahl rat and possibly in patients. The mechanism is uncertain, but preliminary data suggest altered phosphorylation of troponin I and/or T.
How Does Leader’s Support for Environment Promote Organizational Citizenship Behaviour for Environment? A Multi-Theory Perspective

Organizational citizenship behaviour for environment of employees is indispensable in realizing environmental sustainability goals of organizations. However, in the growing literature of employee green behaviour at work, scant attention has been paid on the impact of leader’s specific support for environment, and the mechanisms through which it impacts organizational citizenship behaviour for environment. Drawing upon social exchange theory, self-determination theory and theory of normative conduct, we tested the impact of leader’s support for environment, autonomous motivation for environment and perceived group’s green climate on organizational citizenship behaviour for environment in an integrated model. The sample included 313 executive level employees of green implemented textile and apparel manufacturing factories in Sri Lanka. The results of structural equation modelling showed a direct positive impact of leader’s support for environment on organizational citizenship behaviour for environment. Further, autonomous motivation for environment and perceived group’s green climate were found to be partial mediators between leader’s support for environment and organizational citizenship behaviour for environment. We discussed the theoretical implications for sustainability literature and the managerial implications for organizational practitioners in promoting organizational citizenship behaviour for environment.
Housing, Wealth, Income and Consumption: China and Homeownership Heterogeneity

Impacts on consumer spending in urban China associated with housing value, housing equity, financial assets and household income are evaluated using longitudinal data from the China Family Panel Studies (CFPS) survey. Findings suggest that the housing wealth effect on household consumption in China is much larger than has been shown for developed economies. The larger impact is prospectively related to structural limits on investing which favor real estate ownership, along with the dominant position of housing in total household wealth. We also find that a household's consumption varies across housing tenure. Homeowners having joint ownership of property on average have the highest consumption propensity, while those having sole ownership of property consume the most in response to appreciation in housing wealth.
Virtual histology and remodelling index allow in vivo identification of allegedly high-risk coronary plaques in patients with acute coronary syndromes: a three vessel intravascular ultrasound radiofrequency data analysis.

BACKGROUND Virtual histology (VH) uses intravascular ultrasound (IVUS) radiofrequency spectral analysis to locally identify the morphology and composition of atherosclerotic plaques. We sought to explore in vivo the relation between IVUS-derived thin cap fibro-atheroma (IDTCFA) and remodelling index in patients with acute coronary syndromes using IVUS-VH. METHODS AND RESULTS Twenty-one patients (63 vessels) were enrolled. When compared to cross sectional areas (CSAs) without necrotic core in contact with the lumen (NCCL), CSAs with NCCL had a larger plaque burden 42.8+/-11.5% vs. 32.8+/-11.5%, p<0.001; higher overall necrotic core content [13.8+/-10.7% vs. 2.3+/-7.9% (p<0.001)] and calcified tissue [4.7+/-6.5 vs. 0.66+/-2.1% (p<0.001)]. On average there were 2 IVUS-derived thin cap fibro-atheroma (IDTCFA) per patient. Nearly half of the IDTCFAs had positive remodelling. CONCLUSIONS CSAs with NCCL had worse morphological profiles than those with no NCCL. The simultaneous and more detailed assessment of IDTCFA and remodelling index identifies a reduced number of allegedly high-risk plaques. The findings of this study may have important clinical implications, since they shed light into a possible method of identiying potentially high-risk plaques suitable for pharmacological and/or local treatment.
Association of nasomaxillary asymmetry in children with unilateral cleft lip and palate and their parents.

OBJECTIVE It has been suggested previously that increased width of midfacial structures is associated with the development of palatal clefting. The aim of this study was to evaluate the association of transverse craniofacial asymmetry between children with unilateral cleft lip and palate (UCLP) and their parents. Specifically, we hypothesized that parental transverse craniofacial asymmetry is a risk factor associated with the development of asymmetry in children with UCLP. DESIGN Retrospective cross-sectional investigation including affected children and their noncleft parents. PATIENTS, PARTICIPANTS A total of 64 children-parent sets of data (32 child-biological mother + 32 child-biological father) were included. Subject records included posteroanterior cephalometric radiographs obtained from 29 Costa Rican families with UCLP. MAIN OUTCOME MEASURES The side of parental nasal asymmetry was significantly associated with the side of cleft in their children. For the majority of parents with children suffering from a left cleft, nasal width was larger on the left, compared with the right side. Similarly, in the majority of parents with children suffering from a right cleft, nasal width was larger on the right, compared with the left side. CONCLUSION The results suggest that unilaterally increased nasomaxillary width in parents may play a key role in the development of ipsilateral palatal clefting in their offspring, therefore underscoring the importance of craniofacial form as a genetic etiologic factor in the genesis of clefting. Better understanding of the role of craniofacial form in cleft development will ultimately allow for the assessment of risk for cleft lip and palate.
Prospective Cohort Study of Hospital Palliative Care Teams for Inpatients With Advanced Cancer: Earlier Consultation Is Associated With Larger Cost-Saving Effect.

PURPOSE Previous studies report that early palliative care is associated with clinical benefits, but there is limited evidence on economic impact. This article addresses the research question: Does timing of palliative care have an impact on its effect on cost? PATIENTS AND METHODS Using a prospective, observational design, clinical and cost data were collected for adult patients with an advanced cancer diagnosis admitted to five US hospitals from 2007 to 2011. The sample for economic evaluation was 969 patients; 256 were seen by a palliative care consultation team, and 713 received usual care only. Subsamples were created according to time to consult after admission. Propensity score weights were calculated, matching the treatment and comparison arms specific to each subsample on observed confounders. Generalized linear models with a γ distribution and a log link were applied to estimate the mean treatment effect on cost within subsamples. RESULTS Earlier consultation is associated with a larger effect on total direct cost. Intervention within 6 days is estimated to reduce costs by -$1,312 (95% CI, -$2,568 to -$56; P = .04) compared with no intervention and intervention within 2 days by -$2,280 (95% CI, -$3,438 to -$1,122; P < .001); these reductions are equivalent to a 14% and a 24% reduction, respectively, in cost of hospital stay. CONCLUSION Earlier palliative care consultation during hospital admission is associated with lower cost of hospital stay for patients admitted with an advanced cancer diagnosis. These findings are consistent with a growing body of research on quality and survival suggesting that early palliative care should be more widely implemented.