Miracle-dz/UniFAR-FTUs huggingface dataset:
Cigarette smoking and histologic type of lung cancer in men.

STUDY OBJECTIVES To determine whether intensity, duration, age at initiation, and cessation of cigarette smoking act differently in the development of various histologic types of lung cancer. DESIGN A case-control study among deceased men who underwent autopsy, a procedure that involves approximately 73% of all local deaths. SETTING The Province of Trieste in northeastern Italy PARTICIPANTS Seven hundred fifty-five patients with lung cancer, including 267 with squamous cell carcinoma, 218 with small cell carcinoma, 90 with large cell carcinoma, 158 with adenocarcinoma, and 22 with other histologic types, and 755 control subjects who had died of causes other than chronic lung diseases and certain tumors. Information on smoking habits, residential history, and occupational exposure was obtained from each subject's next of kin. RESULTS Compared with nonsmokers, the odds ratio (OR) for current smokers was 13.4 for all types combined, 18.8 for squamous cell carcinoma, 14.3 for small cell carcinoma, 34.3 for large cell carcinoma, and 7.9 for adenocarcinoma. Intensity of smoking, duration, age at starting, and dose were all directly associated with all histologic types of lung cancer, although the OR was lower for adenocarcinoma than for other cell types. When results were restricted to ever smokers, exposure-response curves were similar across histologic types. The risk of lung cancer attributable to smoking was 88% for all types combined, 91% for squamous cell carcinoma, 89% for small cell carcinoma, 95% for large cell carcinoma, and 82% for adenocarcinoma. CONCLUSIONS This study confirms that cigarette smoking causes all types of lung cancer, but the proportion of cases attributable to smoking is lower for adenocarcinoma than for other types, due to a higher proportion of nonsmokers.
A Survey of Learning in Multiagent Environments: Dealing with Non-Stationarity

The key challenge in multiagent learning is learning a best response to the behaviour of other agents, which may be non-stationary: if the other agents adapt their strategy as well, the learning target moves. Disparate streams of research have approached non-stationarity from several angles, which make a variety of implicit assumptions that make it hard to keep an overview of the state of the art and to validate the innovation and significance of new works. This survey presents a coherent overview of work that addresses opponent-induced non-stationarity with tools from game theory, reinforcement learning and multi-armed bandits. Further, we reflect on the principle approaches how algorithms model and cope with this non-stationarity, arriving at a new framework and five categories (in increasing order of sophistication): ignore, forget, respond to target models, learn models, and theory of mind. A wide range of state-of-the-art algorithms is classified into a taxonomy, using these categories and key characteristics of the environment (e.g., observability) and adaptation behaviour of the opponents (e.g., smooth, abrupt). To clarify even further we present illustrative variations of one domain, contrasting the strengths and limitations of each category. Finally, we discuss in which environments the different approaches yield most merit, and point to promising avenues of future research.
Place-based network organizations and embedded entrepreneurial learning: Emerging paths to sustainability

Purpose The purpose of this paper is to develop an original six-phase model describing entrepreneurial learning in the transition of place-based enterprises toward a sustainable exploitation of natural common resources (commons). Design/methodology/approach The six-phase model proposed by this study explains the learning processes involving place-based enterprises through two important existing theories: adaptive co-management and Lachmann’s evolutionary, embedded theory of entrepreneurship. The proposed model integrates these two theories on the basis of a longitudinal case study on the fishing enterprises in an Italian marine protected area (MPA). Findings In the case study, the success factors identified by the adaptive co-management literature proved important in enabling an embedded entrepreneurial learning process consistent with Lachmann’s view. The case analysis allowed the authors to cluster these learning processes around six phases. Further, even if traditional fishing is not knowledge-intensive, this case shows the transition to a sustainable business model required intense efforts of educated institutional work and scientific research. Interestingly, the key learning processes were enabled by the emergence of a larger, networked social entity (a network form of organization) including the community of fishermen, the MPA management and a network of scientists studying the marine area ecosystem. Research limitations/implications This study is explorative and relies on a single case study. Despite this limitation, it opens up new research paths in the fields of entrepreneurship, institutional work, network organizations and adaptive management of the commons. Originality/value This study is strongly interdisciplinary; it proposes an original model based on a theoretical view that is highly innovative for organization and management studies; and addresses a relevant but overlooked issue with important societal implications.
Optimal Decomposition for Large-Scale Infrastructure-Based Wireless Networks

The fundamental idea of network decomposition is to break a large-scale network into smaller parts such that the subnetworks can operate in parallel, each with a much lower dimensionality. For large-scale wireless networks, the cellular structure is based on the idea of network decomposition, where the network is decomposed into multiple subnetworks, i.e., cells, according to the coverage of each base-station (BS). Such a decomposition scheme, nevertheless, leads to strong interference among subnetworks, which becomes increasingly significant as the density of BSs grows. For the next-generation cellular network, where a massive amount of BSs need to be deployed to meet the ever-increasing demand of high data rate, it is of paramount importance to develop efficient network decomposition schemes to replace the current cellular structure. How to build such a decomposition framework, unfortunately, has remained largely unknown. This paper aims to establish a network decomposition theory for large-scale wireless networks from a graph-theoretic point of view. Specifically, we start from a novel bipartite graph representation of an infrastructure-based wireless network and show that in general the optimal network decomposition can be formulated as a graph partitioning problem. For demonstration, we focus on maximizing the number of subgraphs for a given cut ratio constraint and propose a binary search based spectral relaxation (BSSR) algorithm to solve it in two loops. The performance of the proposed BSSR algorithm is further examined and compared with the current cellular structure and BS clustering in various scenarios. Significant gains are shown to be achieved by the proposed BSSR algorithm, which corroborates that the optimal network decomposition of next-generation cellular networks should be performed based on a bipartite graph, where the geographical information of BSs and users are both included.
What can we learn? Adult outcomes in children of seriously mentally ill mothers.

PROBLEM Information is lacking about the experiences, needs of, and interventions for children of seriously mentally ill mothers. METHODS Quantitative and qualitative methods of inquiry were used to retrospectively explore the characteristics and needs of adult children of seriously mentally ill mothers. The sample (N = 40) was recruited by referral and media advertisements. Childhood variables related to attachment, family environment, and parenting were compared to adult well-being outcomes of depression, quality of life, sense of coherence, and self-esteem. Participants also responded to the question "What other question should have been included in this study about your experience as the child of a seriously mentally ill mother? " and, additionally, spontaneously added their own clarifications of their answers to the survey questions. FINDINGS It was apparent that the childhoods of participants were disruptive and often painful. Over half of the sample reported having their own diagnosis of depression in adulthood. Despite these factors, most members of the study sample were functioning well in adulthood, most often as a result of their own initiative. CONCLUSIONS A high rate of depression in adulthood and participants' own descriptions of their painful memories and experiences of childhood identifies that more can and should be done to assist children of mentally ill mothers to cope with their environments. Interventions at various times in childhood are described.
Prevalence and Risk Factors Among Minors for Online Sexual Solicitations and Interactions With Adults

The research on online child sexual victimization has mainly focused on the sexual solicitation of minors (i.e., sexual requests by an adult), with scarce information available on sexual interactions (e.g., cybersex or meeting in person) in which a minor is exploited by an adult. In the present study, we analyzed the prevalence and risk factors associated with both sexual solicitations and interactions of minors with adults. The sample included 2,731 minors between 12 and 15 years old (50.6% female). The minors completed several self-report questionnaires about sexual solicitations and interactions with adults, including possible risk factors (e.g., sociodemographic variables, Internet use, and psychological adjustment). Of the participants, 15.6% of girls and 9.3% of boys reported sexual solicitations, and 8.2% of girls and 7.4% of boys reported sexualized interactions with adults. Among the variables studied, several appeared related to both sexual solicitations and interactions: older age, having been involved in sexting, being a victim of cyberbullying, having unknown people in friends list, using chat, time spent online on a weekday, and depression symptoms. Gender (being female), using video chat, and instant messaging by computer were significant variables for sexual solicitation but not for sexual interaction; participation in online games was significant only for sexual interactions. Finally, minors reporting sexual interactions presented a higher risk profile than those reporting only sexual solicitations. These findings highlight the relevance of distinguishing between sexual solicitations and sexual interactions and suggest important avenues for prevention programs.
Heparin antagonizes cisplatin resistance of A2780 ovarian cancer cells by affecting the Wnt signaling pathway

Low molecular weight heparin (LMWH), the guideline based drug for prophylaxis and treatment of cancer-associated thrombosis, was recently shown to sensitize cisplatin resistant A2780cis human ovarian cancer cells for cisplatin cytotoxicity upon 24 h pretreatment with 50 μg × mL−1 of the LMWH tinzaparin in vitro, equivalent to a therapeutic dosage. Thereby, LMWH induced sensitization by transcriptional reprogramming of A2780cis cells via not yet elucidated mechanisms that depend on cellular proteoglycans. Here we aim to illuminate the underlying molecular mechanisms of LMWH in sensitizing A2780cis cells for cisplatin. Using TCF/LEF luciferase promotor assay (Top/Flash) we show that resistant A2780cis cells possess a threefold higher Wnt signaling activity compared to A2780 cells. Furthermore, Wnt pathway blockade by FH535 leads to higher cisplatin sensitivity of A2780cis cells. Glypican-3 (GPC3) is upregulated in A2780cis cells in response to LMWH treatment, probably as counter-regulation to sustain the high Wnt activity against LMWH. Hence, LMWH reduces the cisplatin-induced rise in Wnt activity and TCF-4 expression in A2780cis cells, but keeps sensitive A2780 cells unaffected. Consequently, Wnt signaling pathway appears as primary target of LMWH in sensitizing A2780cis cells for cisplatin toxicity. Considering the outstanding role of LMWH in clinical oncology, this finding appears as promising therapeutic option to hamper chemoresistance.
Membrane topology of the cyanobacterial bicarbonate transporter, BicA, a member of the SulP (SLC26A) family

Abstract We have completed the first comprehensive transmembrane topology determination for a member of the ubiquitous and important SulP/SLC26 family of coupled anion transporters found in eukaryotes and prokaryotes. The prokaryotic member that we have mapped, namely BicA from Synechococcus PCC7002, is an important Na+-dependent bicarbonate transporter that is likely to play a major role in global primary productivity via the CO2 concentrating mechanism in cyanobacteria. We experimentally determined the topology based on phoA-lacZ topology mapping combined with reference to a range of predictive models based on hydropathy analysis and positive charge distribution. The 12-TMH structure for BicA is characterized by tight turns between several pairs of TMH and it features a prominent cytoplasmically-located STAS domain that is characteristic of the SulP family. A key difference from previous predicted models is that we identify a cytoplasmic loop between helices 8 and 9 where previous models suggested a TMH. This region includes a highly conserved motif that defines the SulP family. The identification of this region as cytoplasmic, rather than transmembrane, has implications for the function and perhaps regulation of SulP family members. This finding is used to reinterpret mutagenesis data relating to highly conserved residues in this region from both plant and human SulP transporters.
Modeling DNA Double-Strand Break Repair Kinetics as an Epiregulated Cell-Community-Wide (Epicellcom) Response to Radiation Stress

The multicellular signaling model (MULTISIG1) was recently introduced to simulate the kinetics of repair of DNA double-strand breaks (DSBs) that were induced in confluent (non-dividing) cultured cells by a very low radiation dose where at most a single induced DSB would be expected in a given cell nucleus. The repair kinetics was modeled as representing what is now called an epigenetically-regulated (epiregulated) cell-community-wide (epicellcom) response to radiation stress. DSB repair initiation is assumed to require a threshold number of cells with DSBs participating in intercellular stress-response signaling. The MULTISIG1 model is extended in this study to apply to moderate doses where several DSBs can occur on the same DNA molecule. The repair of multiple breaks on the same molecule is treated as sequential stochastic events. For cells of differing genetic characteristics and epigenetic statuses, relationships are provided for evaluating the relative susceptibility (RS) for DSB induction, relative repair capacity (RRC) for DSB repair, and relative epiapoptosis capacity (REC), for epigenetically regulated apoptosis. The modified MULTISIG1 model is used to characterize the expected repair kinetics for confluent, human lung fibroblasts (MRC-5 line) briefly exposed in vitro to 90-kV x-rays. Possible application of the model to biological dosimetry is also discussed.
Morphological and Histological Effects of Radiofrequency and Laser (KTP and Nd:YAG) Treatment of the Inferior Turbinates in Animals

The aim of this study was to evaluate the short and medium-term effects of radiofrequency (RF) and potassium titanyl phosphate (KTP) and neodymium-yttrium-aluminum garnet (Nd:YAG) laser treatment on the inferior turbinate mucosa in a porcine model. Following randomization, the inferior turbinates were treated either with RF submucosally or with the KTP or the Nd:YAG laser on the surface under videoendoscopic control. Tissue samples were taken at the end of postoperative weeks 1 and 6, and were evaluated macroscopically and histopathologically. Scanning electron microscopy was implemented to demonstrate the morphological changes in the respiratory epithelium. Six weeks following the RF procedure, the mucosa was intact in all cases, and the volume of the inferior turbinates was reduced in the majority of the cases. Although a volume reduction occurred in both laser groups, more complications associated with the healing procedure were noted. With hematoxylin and eosin and periodic acid–Schiff staining, intact epithelium, and submucosal glands remained after the RF procedures at the end of postoperative week 6. Following the KTP-laser intervention, necrotizing sialometaplasia and cartilage destruction occurred, and squamous metaplasia was also apparent in the Nd:YAG group. In both laser groups, dilated glands with excess mucus were seen. The scanning electron microscopic findings demonstrated that cilia were present in all cases. In conclusion, the medium-term macroscopic results were similar in all 3 groups, but the postoperative complications were less following the RF procedure. RF procedure is minimally invasive due to the submucosal intervention that leads to a painless, function preserving recovery.
Nuclear factor-kappaB mediates angiogenesis and metastasis of human bladder cancer through the regulation of interleukin-8.

PURPOSE Interleukin (IL)-8 is an important mediator of angiogenesis, tumorigenicity, and metastasis in transitional cell carcinoma (TCC) of the bladder. Nuclear factor kappaB (NF-kappaB)/relA regulates IL-8 expression in several neoplasms. The purpose of this study was to determine whether the organ microenvironment (hypoxia, acidosis) regulates the expression of IL-8 in TCC via NF-kappaB, and whether inhibition of NF-kappaB function by mutant IkappaB-alpha prevents induction of IL-8 expression. EXPERIMENTAL DESIGN IL-8 mRNA expression and protein production by human TCC cell lines (UM-UC-14, HTB-9, RT-4, KU-7 and 253J B-V) were measured by Northern blot analysis and ELISA under acidic (pH 7.35-6.0) and hypoxic (1.0% O(2)) conditions. The involvement of NF-kappaB and activator protein 1 in the regulation of IL-8 production was evaluated by electrophoretic mobility shift assay. Furthermore, the tumorigenicity and metastatic potential of UM-UC-14 cells were determined after transfection with mutant IkappaB-alpha. RESULTS We found that acidic and hypoxic conditions increased IL-8 mRNA expression and protein production by several, but not all, TCC cell lines evaluated. NF-kappaB, but not activator protein 1, was inducibly activated in UM-UC-14 under both acidic and hypoxic conditions, but not in UM-UC-14 mutant IkappaB-alpha transfectants. Tumor growth and lymph node metastasis were inhibited in UM-UC-14 mutant IkappaB-alpha transfectants compared with UM-UC-14 controls. This effect was associated with the inhibition of IL-8 production, cellular proliferation, and angiogenesis. CONCLUSIONS These results suggest that TCCs of the bladder have heterogenic responses to physicochemical changes in the microenvironment and identify NF-kappaB as a potential molecular target for therapy.
Event-related potential markers of expectation violation in an artificial grammar learning task

To investigate the neural correlates of artificial grammar learning, we recorded the electroencephalogram while experimental participants listened to phonological sequences. We compared event-related potential responses to expectancy violations in two participant conditions; training and a no-training control group. During the test phase, participants in both types of training heard ill-formed sequences. This allowed us to explore the relationship among expectancy violations because of three aspects of a stimulus: physical characteristics, the mental representation of the vocabulary of an artificial grammar, and learned patterns of sequential regularities. Unexpected phonological elements in the test sequences elicited N2b/Pb components. Difference waveforms demonstrated that training had a significant effect on the event-related potential response to deviant items.
Evolution of human papillomavirus type 18: an ancient phylogenetic root in Africa and intratype diversity reflect coevolution with human ethnic groups

Papillomaviruses are an ideal model system for the study of DNA virus evolution. On several levels, phylogenetic trees of papillomaviruses reflect the relationship of their hosts. Papillomaviruses isolated from remotely related vertebrates form major branches. One branch of human papillomaviruses (HPVs) includes an ape and two monkey papillomaviruses, possibly because the diversification of the viruses predated the separation of the infected-primate taxa. This hypothesis predicts that the root of the evolution of some if not all HPV types should point to Africa, since humans evolved from nonhuman primates in this continent. We tested this hypothesis and compared the genomic sequences of HPV type 18 (HPV-18) isolates from four continents. Diversity within HPV-18 correlates with patterns of the evolution and spread of Homo sapiens: HPV-18 variants, just like HPV-16 variants, are specific for the major human races, with maximal diversity in Africa. Outgroup rooting of the HPV-18 tree against HPV-45, which is closely related to HPV-18, identifies African HPV-18 variants at the root of the tree. The identification of an African HPV-45 isolate further reduces the evolutionary distance between HPV-18 and HPV-45. HPV-18 variants from Amazonian Indians are the closest relatives to those from Japanese and Chinese patients and suggest that a single point mutation in the phylogenetically evaluated genomic segment represents at least 12,000 years of evolution. We estimate that diversity within HPV-18 and probably within other HPV types evolved over a period of more than 200,000 years and that diversity between HPV types evolved over several million years.
In the backwater of convective dialysis: decreased 25-hydroxyvitamin D levels following the switch to online hemodiafiltration.

BACKGROUND/AIMS Vitamin D deficiency and elevated serum fibroblast growth factor-23 (FGF23) levels are hallmark features and surrogate markers of adverse clinical outcomes in patients with chronic kidney disease (CKD). Convection of molecules over the dialysis membrane during online hemodiafiltration (ol-HDF) increases the removal of larger waste molecules compared with traditional high-flux hemodialysis (HD). The primary aim of this study was to explore the long-term impact of ol-HDF on serum 25(OH)D and FGF23. METHOD An observational, prospective, noncomparator study including 35 patients who were switched from HD to ol-HDF. Serum 25(OH)D and FGF23 were measured at baseline (i.e., time of switch to ol-HDF) and at 6, 12, and 24 months. RESULTS At follow-up time points, there was a significant reduction in serum 25(OH)D compared with baseline (p<0.0001) whereas FGF23 was unaltered (p>0.05). The decrease in 25(OH)D was more prominent in individuals with higher baseline 25(OH)D levels. CONCLUSION Ol-HDF may lower systemic 25(OH)D levels by convective mechanisms although the clinical significance remains unknown. Further controlled studies are warranted to replicate these findings in larger patient cohorts.