Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationship between genetic alterations and prognosis in sporadic colorectal cancer

Because chromosomal chromosomal instability (CIN) and microsatellite instability (MSI) are important genetic alterations in colorectal cancers, we classified the sporadic colorectal cancers (CRC) on the status of the CIN and MSI and explored their molecular profiles. A total of 213 colorectal tumors were collected for analysis of DNA ploidy, MSI, loss of heterozygosity (LOH), mutation of p53 (exons 5 to 9), Ki‐ras (exons 1 and 2) and BRAF (V599E). Relationships between clinicopathological variables and molecular analyses were analyzed with the χ2 test (Yates' correction). Kaplan–Meier survival curves were compared using log‐rank test. Variables with p < 0.1 were entered into the Cox regression hazard model for multivariate analysis. High microsatellite instability (MSI‐H) existed in 19 tumors (8.9%), which were more likely to be right‐sided (31.6%) with poor differentiation (26.3%). Seventy‐one (33.3%) tumors were diploid and 142 (66.7%) were aneuploid. Mutations in p53, Ki‐ras and BRAF were found in 45.1%, 41.8% and 4.2% of tumors, respectively. Based on MSI, and CIN, 3 classes were defined: (i) High microsatellite instability MSI‐H tumors: young age, high carcinoembryonic antigen (CEA) level, right colon, poorly differentiated, mucin production, high BRAF mutation, lower allelic loss and relatively good prognosis; (ii) Microsatellite stability (MSS) diploid tumors: right colon, poorly differentiated, less infiltrative tumor, mucin production, lower allelic loss and low p53, BRAF mutation; (iii) MSS aneuploid tumors: more infiltrative invasion, greater allelic loss and high p53 mutation. According to multivariate analysis, tumor stage and p53 mutation were significantly associated with disease progression. The MSS diploid and MSS aneuploid CRCs could be subtyped with p53 mutation and had different prognostic outcome and molecular profiles. The 4‐year disease‐free survival (DFS) of patients with MSS‐diploid, wild‐type p53 tumors was 67% and significantly higher than those of patients with MSS‐diploid, mutant p53 CRC (30%, p = 0.003). The same trend was found in patients with MSS‐aneuploid CRC(wild p53 vs. mutant p53, 64% vs. 41%, p = 0.009). We concluded that CIN, MSI and p53 mutation status might be used as a multiple parameter profile for the prognosis of sporadic colorectal cancer. © 2005 Wiley‐Liss, Inc.
Climate impacts of ice nucleation

[1] Several different ice nucleation parameterizations in two different General Circulation Models (GCMs) are used to understand the effects of ice nucleation on the mean climate state, and the Aerosol Indirect Effects (AIE) of cirrus clouds on climate. Simulations have a range of ice microphysical states that are consistent with the spread of observations, but many simulations have higher present-day ice crystal number concentrations than in-situ observations. These different states result from different parameterizations of ice cloud nucleation processes, and feature different balances of homogeneous and heterogeneous nucleation. Black carbon aerosols have a small (−0.06 Wm−2) and not statistically significant AIE when included as ice nuclei, for nucleation efficiencies within the range of laboratory measurements. Indirect effects of anthropogenic aerosols on cirrus clouds occur as a consequence of increasing anthropogenic sulfur emissions with different mechanisms important in different models. In one model this is due to increases in homogeneous nucleation fraction, and in the other due to increases in heterogeneous nucleation with coated dust. The magnitude of the effect is the same however. The resulting ice AIE does not seem strongly dependent on the balance between homogeneous and heterogeneous ice nucleation. Regional effects can reach several Wm−2. Indirect effects are slightly larger for those states with less homogeneous nucleation and lower ice number concentration in the base state. The total ice AIE is estimated at 0.27 ± 0.10 Wm−2 (1σ uncertainty). This represents a 20% offset of the simulated total shortwave AIE for ice and liquid clouds of −1.6 Wm−2.
Enhanced continuing care provided in parallel to intensive outpatient treatment does not improve outcomes for patients with cocaine dependence.

OBJECTIVE This study tested whether the addition of an enhanced continuing care (ECC) intervention that combined in-person and telephone sessions and began in the first week of treatment improved outcomes for cocaine-dependent patients entering an intensive outpatient program (IOP). METHOD Participants (N = 152) were randomized to IOP treatment as usual (TAU) or IOP plus 12 months of ECC. ECC included cognitive-behavioral therapy elements to increase coping skills, as well as monetary incentives for attendance. It was provided by counselors situated at a separate clinical research facility who did not provide IOP. The primary outcomes measured were (a) cocaine urine toxicology and (b) good clinical outcome, as indicated by abstinence from all drugs and from heavy alcohol use. Secondary outcomes were frequency of abstinent days, cocaine use days, and heavy drinking days. Follow-ups were conducted at 3, 6, 9, and 12 months after baseline. RESULTS Patients in ECC completed a mean of 18 sessions. Contrary to the hypotheses, patients in TAU had better scores on both the cocaine urine toxicology and the good clinical outcome measures than those in ECC, as indicated by significant Group × Time interactions (cocaine urine toxicology, p = .0025; abstinence composite, p = .017). These results were not moderated by substance use before or early in treatment or by IOP attendance. Results with the secondary outcomes also did not favor ECC over TAU. CONCLUSIONS Continuing care that is not well integrated with the primary treatment program may interfere in some way with the therapeutic process, particularly when it is implemented shortly after intake.
Comparing ESC and iPSC—Based Models for Human Genetic Disorders

Traditionally, human disorders were studied using animal models or somatic cells taken from patients. Such studies enabled the analysis of the molecular mechanisms of numerous disorders, and led to the discovery of new treatments. Yet, these systems are limited or even irrelevant in modeling multiple genetic diseases. The isolation of human embryonic stem cells (ESCs) from diseased blastocysts, the derivation of induced pluripotent stem cells (iPSCs) from patients’ somatic cells, and the new technologies for genome editing of pluripotent stem cells have opened a new window of opportunities in the field of disease modeling, and enabled studying diseases that couldn’t be modeled in the past. Importantly, despite the high similarity between ESCs and iPSCs, there are several fundamental differences between these cells, which have important implications regarding disease modeling. In this review we compare ESC-based models to iPSC-based models, and highlight the advantages and disadvantages of each system. We further suggest a roadmap for how to choose the optimal strategy to model each specific disorder.
The Interplay among Category Characteristics, Customer Characteristics, and Customer Activities on in-Store Decision Making

The authors explore product category and customer characteristics that affect consumers’ likelihood of engaging in unplanned purchases. In addition, they examine consumer activities that can exacerbate or limit these effects. The authors employ a hierarchical modeling approach to test their hypotheses using a data set of in-store intercept interviews conducted with 2300 consumers across 28 stores. The results show that category characteristics, such as purchase frequency and displays, and customer characteristics, such as household size and gender, affect in-store decision making. Moreover, although the analysis reveals that the baseline probability of an unplanned purchase is 46%, the contextual factors can drive this probability as high as 93%. The results support the predictions that list use, more frequent trips, limiting the aisles visited, limiting time spent in the store, and paying by cash are effective strategies for decreasing the likelihood of making unplanned purchases.
Mutations of the cystic fibrosis gene in patients with chronic pancreatitis

OBJECTIVE:Several studies have reported an increased frequency of cystic fibrosis gene mutations in idiopathic but not in alcoholic chronic pancreatitis. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis has not been analyzed. The aim of our study was to determine the frequency of cystic fibrosis gene mutations in patients with chronic pancreatitis with long-term follow-up and to see whether patients with mutations have a clinically different natural course compared to those without mutations.METHODS:Eighty two patients with chronic pancreatitis and 11 patients with recurrent acute pancreatitis of our well defined pancreatitis cohort were screened for the 31 most common cystic fibrosis gene mutations. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis was assessed.RESULTS:A cystic fibrosis gene mutation was detected in five of 49 patients with alcoholic chronic pancreatitis (10.2%; 2.3 times the expected frequency) and in three of 14 patients with idiopathic-juvenile chronic pancreatitis (21.4%; 4.8 times the expected frequency). No mutations were found in the remaining patients with chronic pancreatitis of rare causes, hereditary pancreatitis, and recurrent acute pancreatitis. The frequency of pancreatic calcifications was significantly higher in patients with alcoholic chronic pancreatitis without mutations. This result was not confirmed in patients with idiopathic-juvenile chronic pancreatitis. The duration of pain and the frequency of exocrine and endocrine insufficiency was comparable in both subgroups irrespective of the mutation status.CONCLUSION:Our data indicate a significantly increased frequency of cystic fibrosis gene mutations both in patients with alcoholic and idiopathic-juvenile chronic pancreatitis. The natural course was similar in patients with mutations compared to those without mutations.
Partner choice creates competitive altruism in humans

Reciprocal altruism has been the backbone of research on the evolution of altruistic behaviour towards non-kin, but recent research has begun to apply costly signalling theory to this problem. In addition to signalling resources or abilities, public generosity could function as a costly signal of cooperative intent, benefiting altruists in terms of (i) better access to cooperative relationships and (ii) greater cooperation within those relationships. When future interaction partners can choose with whom they wish to interact, this could lead to competition to be more generous than others. Little empirical work has tested for the possible existence of this ‘competitive altruism’. Using a cooperative monetary game with and without opportunities for partner choice and signalling cooperative intent, we show here that people actively compete to be more generous than others when they can benefit from being chosen for cooperative partnerships, and the most generous people are correspondingly chosen more often as cooperative partners. We also found evidence for increased scepticism of altruistic signals when the potential reputational benefits for dishonest signalling were high. Thus, this work supports the hypothesis that public generosity can be a signal of cooperative intent, which people sometimes ‘fake’ when conditions permit it.
Blocks+: a non-redundant database of protein alignment blocks derived from multiple compilations

MOTIVATION As databanks grow, sequence classification and prediction of function by searching protein family databases becomes increasingly valuable. The original Blocks Database, which contains ungapped multiple alignments for families documented in Prosite, can be searched to classify new sequences. However, Prosite is incomplete, and families from other databases are now available to expand coverage of the Blocks Database. RESULTS To take advantage of protein family information present in several existing compilations, we have used five databases to construct Blocks+, a unified database that is built on the PROTOMAT/BLOSUM scoring model and that can be searched using a single algorithm for consistent sequence classification. The LAMA blocks-versus-blocks searching program identifies overlapping protein families, making possible a non-redundant hierarchical compilation. Blocks+ consists of all blocks derived from PROSITE, blocks from Prints not present in PROSITE, blocks from Pfam-A not present in PROSITE or Prints, and so on for ProDom and Domo, for a total of 1995 protein families represented by 8909 blocks, doubling the coverage of the original Blocks Database. A challenge for any procedure aimed at non-redundancy is to retain related but distinct families while discarding those that are duplicates. We illustrate how using multiple compilations can minimize this potential problem by examining the SNF2 family of ATPases, which is detectably similar to distinct families of helicases and ATPases. AVAILABILITY http://blocks.fhcrc. org/
Effects of methamphetamine on trauma patients: A cause of severe metabolic acidosis?

Objective Presentation of a trauma patient with severe unexplained metabolic acidosis, possibly attributable to the vasoconstrictive properties of smokable “crystal” methamphetamine. In addition, a review of trauma registry data was undertaken to determine the effects of methamphetamine on trauma patients. Design Case report and retrospective case-control study. Setting Urban tertiary teaching hospital. Patients Two controls were obtained for each case controlling for age, Injury Severity Score, and mechanism of injury. Patients ≥16 yrs of age with a urine toxicology screen positive for methamphetamine were included. Measurements and Main Results Data were obtained from the trauma registry for the period of January 1994 to June 1995. Trauma patients using methamphetamine had a significantly lower blood alcohol level compared with the control group. Otherwise, there were no significant differences detected in vital signs, laboratory values, procedures, treatment, or outcome between the two groups. Details regarding one patient who presented with severe life-threatening acidosis are presented. Conclusions Trauma patients with recent use of smokable methamphetamine may present with severe acidosis requiring urgent attention and treatment. This acidosis may exaggerate the severity of the actual injury. However, urine testing for methamphetamine does not identify patients who may harbor this acidosis.
COVID-19, new challenges to human safety: a global review

In the context of sustainable human development, human safety has gradually shifted from traditional state and political conflict to social conflict and horizontal inequality, and the pandemic has exacerbated this variation risk. This narrative review includes literature from 40 countries on five continents since 2020, explored and tidy up the impacts of pandemics on human safety based on three perspectives: personal safety, family safety and social safety, refined the macroscopic concept of human safety. The comprehensibility of the global review conclusions is enhanced by combining it with Maslow’s hierarchy of needs. Finally, some novel and comparative results are included to broaden the understanding of the impact of the pandemic, and help policymaker better understand human safety changes from a new perspective.
Three odorant binding proteins may regulate the behavioural response of Chrysopa pallens to plant volatiles and the aphid alarm pheromone (E)‐β‐farnesene

Artificial Chrysopa pallens release is a well‐known method for suppressing aphids, but it is difficult to establish lacewing populations in the field. Understanding the functions of C. pallens odorant‐binding proteins (CpalOBPs) and behavioural responses of C. pallens to plant volatiles and aphid alarm pheromone (E)‐ß‐farnesene has important implications for population establishment after lacewing release. Based on our previous study, five antennae‐enriched CpalOBPs were selected. Sequence alignment and phylogenetic analysis revealed that these five CpalOBPs were Classic OBPs and separated into different clades. Of them, CpalOBP10 clustered in the same clade with aphid OBP7, which mediates the perception of green leaf volatiles and (E)‐ß‐farnesene. Ligand‐binding assays showed 31 compounds, including plant‐derived compounds, pest‐induced volatiles and (E)‐ß‐farnesene, had high binding affinities for at least one of these five CpalOBPs. Of the 31 compounds, the pest‐induced volatiles (Z)−3‐hexenyl hexanoate and 2‐hexyl‐1‐decanol, used in host location by the black bean aphid, elicited significant attractive behavioural responses from C. pallens. Conversely, (E)‐ß‐farnesene elicited strongly repellent behavioural responses. It is conceivable that C. pallens utilizes plant‐derived compounds, pest‐induced volatiles and (E)‐ß‐farnesene as foraging cues. Our studies provide new insights into the interrelationships amongst C. pallens, its prey and the host plants. Compounds that elicited significant behavioural responses from C. pallens were also identified.
A Multiagent Reinforcement Learning Algorithm with Non-linear Dynamics

Several multiagent reinforcement learning (MARL) algorithms have been proposed to optimize agents' decisions. Due to the complexity of the problem, the majority of the previously developed MARL algorithms assumed agents either had some knowledge of the underlying game (such as Nash equilibria) and/or observed other agents actions and the rewards they received. We introduce a new MARL algorithm called theWeighted Policy Learner (WPL), which allows agents to reach a Nash Equilibrium (NE) in benchmark 2-player-2-action games with minimum knowledge. Using WPL, the only feedback an agent needs is its own local reward (the agent does not observe other agents actions or rewards). Furthermore, WPL does not assume that agents know the underlying game or the corresponding Nash Equilibrium a priori. We experimentally show that our algorithm converges in benchmark two-player-two-action games. We also show that our algorithm converges in the challenging Shapley's game where previous MARL algorithms failed to converge without knowing the underlying game or the NE. Furthermore, we show that WPL outperforms the state-of-the-art algorithms in a more realistic setting of 100 agents interacting and learning concurrently. An important aspect of understanding the behavior of a MARL algorithm is analyzing the dynamics of the algorithm: how the policies of multiple learning agents evolve over time as agents interact with one another. Such an analysis not only verifies whether agents using a given MARL algorithm will eventually converge, but also reveals the behavior of the MARL algorithm prior to convergence. We analyze our algorithm in two-player-two-action games and show that symbolically proving WPL's convergence is difficult, because of the non-linear nature of WPL's dynamics, unlike previous MARL algorithms that had either linear or piece-wise-linear dynamics. Instead, we numerically solve WPL's dynamics differential equations and compare the solution to the dynamics of previous MARL algorithms.
A Monte Carlo Study of the Forecasting Performance of Empirical Setar Models

In this paper we investigate the multi-period forecast performance of a number of empirical self exciting threshold autoregressive (SETAR) models that have been proposed in the literature for modeling exchange rates and GNP, amongst other variables. An indicator of when such models are likely to forecast well is suggested based on the serial dependence of regimes, as a means of distinguishing between types of nonlinearities that can be exploited for improved fit versus those that contribute to a better (relative to linear models) out-of-sample forecast performance. In our study the indicator provides a reasonable guide to those models which embody nonlinearities that may yield improved conditional mean forecasts.
Study of Leishmania major-infected macrophages by use of lipophosphoglycan-specific monoclonal antibodies

Leishmania major infection of macrophages is followed by a time-dependent appearance of lipophosphoglycan (LPG) that can be detected on the surface of infected cells by monoclonal antibodies. The origin of these LPG epitopes is probably the intracellular amastigote. LPG epitopes could be detected on the amastigote and the infected macrophage by a number of monoclonal antibodies directed to several distinct determinants on the phosphoglycan moiety. The macrophage-expressed LPG may be modified because, unlike the parasite LPG as expressed on promastigotes or amastigotes, it could not be radiolabeled by galactose oxidase or periodate treatment of infected cells followed by reduction with 3H-labeled sodium borohydride. Some LPG epitopes displayed on the macrophage may be anchored with glycosylphosphatidylinositol, and some may be in the water-soluble phosphoglycan form bound to macrophage integrins involved in its specific recognition. The water-soluble population could be released from the infected macrophage by gentle protease treatment.
Carcinogenesis in Swiss mice by isonicotinic acid hydrazide.

Administration of 0.1% isonicotinic acid hydrazide (INH) in drinking water to 9-week-old Swiss mice for the remainder of their lifetime resulted in the enhancement of pulmonary adenomas. The incidence rose from 14 to 53% in the females and from 10 to 42% in the males, as compared with the controls. The incidence of other tumors in these animals was not increased.
Topographical relationship of the facial and vestibulocochlear nerves in the subarachnoid space and internal auditory canal.

PURPOSE Our purpose was to investigate the topographical relationship of the facial and vestibulocochlear nerves from the brain stem through the internal auditory canal. METHODS We dissected 15 formalin-fixed cadaveric heads and performed MR examinations in 35 healthy subjects in order to examine the topographical relationship of the facial and vestibulocochlear nerves. The cadaveric dissections and the in vivo MR imaging findings were compared indirectly. RESULTS The relationship between the facial and vestibulocochlear nerves showed some variation among individuals and according to the location of the nerves within the cisterns or canal. Near the brain stem, 53% of the vestibulocochlear nerves were partially segmented on MR images. The vestibulocochlear nerve was completely divided into separate nerves only in the most lateral portion of the canal, except in three cadaveric dissections, in which separation of the superior vestibular nerve was seen near the brain stem. The facial and cochlear nerves were of similar size on 36% of the MR images. The superior vestibular nerve was larger than the inferior vestibular nerve on 81% of the MR images. CONCLUSION The appearance of the facial and vestibulocochlear nerves was variable but followed certain consistent patterns.