Miracle-dz/UniFAR-FTUs huggingface dataset:
Approach to cannabis use disorder in primary care: focus on youth and other high-risk users.

OBJECTIVE To review the clinical features and complications of at-risk cannabis use and cannabis use disorder, and to outline an office-based protocol for screening, identifying, and managing this disorder. SOURCES OF INFORMATION PubMed was searched for controlled trials, observational studies, and reviews on cannabis use among adolescents and young adults; cannabis-related medical and psychiatric harms; cannabis use disorder and its treatment; and lower-risk cannabis use guidelines. MAIN MESSAGE Physicians should ask all patients about cannabis use. They should ask adolescents and young adults and those at highest risk of cannabis-related harms (those with concurrent psychiatric or substance use disorders) more frequently. Physicians should also ask about cannabis use in patients who have problems that could be caused by cannabis, such as mood disorders, psychosis, and respiratory symptoms. In patients who report cannabis use, physicians should inquire about frequency and amount, tolerance and withdrawal symptoms, attempts to reduce use, and cannabis-related harms. Lower-risk cannabis users smoke, inhale, or ingest cannabis occasionally without evidence of school, work, or social dysfunction; those with problematic use often use cannabis daily or almost daily, have difficulty reducing their use, and have impaired school, work, or social functioning. Physicians should offer all patients with problematic use brief advice and counseling, focusing on the health effects of cannabis and setting a goal of abstinence (some higher-risk groups should not use cannabis at all) or reduced use, and they should provide practical strategies to reduce cannabis use. Physicians should incorporate simple motivational interviewing techniques into the counseling sessions. They should refer those patients who are unable to reduce use or who are experiencing harms from cannabis use to specialized care, while ensuring those patients remain connected to primary care. As well, physicians should give information on lower-risk cannabis use to all cannabis users. CONCLUSION Physicians should screen all patients in their practices at least once for cannabis use, especially those who have problems that might be caused by cannabis. Physicians should screen those at higher risk more often, at least annually. Lower-risk cannabis use should be distinguished from problematic use. Brief counseling should be provided to those with problematic use; these patients should be referred to specialists if they are unable to reduce or cease use.
Cytoskeletal protein P41 is required to anchor the terminal organelle of the wall‐less prokaryote Mycoplasma pneumoniae

The cell wall‐less prokaryote Mycoplasma pneumoniae approaches the minimal requirements for a cell yet produces a complex terminal organelle that mediates cytadherence and gliding motility. Here we explored the molecular nature of the M. pneumoniae gliding machinery, utilizing fluorescent protein fusions and digital microcinematography to characterize gliding‐altered mutants having transposon insertions in MPN311, encoding the cytoskeletal protein P41. Disruption of MPN311 resulted in loss of P41 and P24, the downstream gene product. Gliding ceases in wild‐type M. pneumoniae during terminal organelle development, which occurs at the cell poles adjacent to an existing structure. In contrast, terminal organelle development in MPN311 mutants did not necessarily coincide with gliding cessation, and new terminal organelles frequently formed at lateral sites. Furthermore, new terminal organelles exhibited gliding capacity quickly, unlike wild‐type M. pneumoniae. P41 and P24 localize at the base of the terminal organelle; in their absence this structure detached from the cell body of motile and dividing cells but retained gliding capacity and thus constitutes the gliding apparatus. Recombinant wild‐type P41 restored cell integrity, establishing a role for this protein in anchoring the terminal organelle to the cell body.
Circadian Blood Pressure and Heart Rate Changes in Patients in a Persistent Vegetative State After Traumatic Brain Injury

Alteration of autonomic nervous system regulation is known to be present in the persistent vegetative state after traumatic brain injury, termed the dysautonomic syndrome. This study assessed the circadian blood pressure and heart rate pattern and variability in the persistent vegetative state through noninvasive 24‐hour ambulatory blood pressure monitoring. The study was performed in 20 subjects: 10 patients (six men and four women; mean age, 29.5±9.9 years; range, 19–39 years) in a vegetative state (mean, 27.3±5.6 days after trauma) and 10 healthy subjects as controls (six men and four women; mean age, 28±5.7 years; range, 29–37 years). The patients showed a blood pressure nondipper pattern; 24‐hour, daytime, and nighttime values of blood pressure and heart rate were significantly higher in patients than in controls. The day‐night difference in heart rate and blood pressure was also significantly lower in patients. Finally, SD and variation coefficients were significantly lower in patients. The results show changes in the variability and circadian blood pressure and heart rate patterns in persistent vegetative state patients with dysautonomic syndrome, as an expression of the sympathetic‐parasympathetic activity imbalance in the control of vasomotor tone.
Branchio-OTO-Renal Dysplasia in Three Families

Branchio-oto-renal dysplasia, often called the BOR syndrome, in its full expression consists of 1) hearing loss of conductive, sensorineural, or mixed type; 2) preauricular pits; 3) auricular deformities; 4) lateral cervical sinuses, cysts, or fistulas; and 5) renal malformations. The condition is inherited in an autosomal dominant mode. The findings in three affected families are described, and pertinent genetic and clinical aspects are discussed. The potential seriousness of the renal and aural malformations stresses the importance of early recognition of this syndrome.
Corticotropin-Releasing Factor within the Central Nucleus of the Amygdala Mediates Enhanced Ethanol Self-Administration in Withdrawn, Ethanol-Dependent Rats

Alcohol dependence is characterized by excessive consumption, loss of control over intake, and the presence of a withdrawal syndrome, including both motivational and physical symptoms. The motivational symptoms, including anxiety, have been hypothesized to be important factors eliciting excessive drinking during abstinence. Previous work has shown that ethanol-dependent rats also display enhanced anxiety-like behaviors and enhanced ethanol self-administration during withdrawal, likely resulting from dysregulation of brain corticotropin-releasing factor (CRF) stress systems. The present study was designed to explore the brain sites within the extended amygdala [central nucleus of the amygdala (CeA), lateral bed nucleus of the stria terminalis (BNST), and nucleus accumbens shell (NAcSh)] that mediate the increased ethanol self-administration observed during withdrawal. Ethanol-dependent animals showed an increase in ethanol self-administration after acute withdrawal relative to nondependent controls. The CRF antagonist d-Phe-CRF12–41 ([d-Phe12,Nle21,38,Cα MeLeu37]-rCRF(12–41)) was administered into the CeA, lateral BNST, or NAcSh of acute-withdrawn dependent and nondependent rats. Administered into the CeA, the antagonist reduced ethanol self-administration in dependent animals, with no effect in nondependent animals. Administration of d-Phe-CRF12–41 into the lateral BNST and NAcSh was without effect on ethanol self-administration in dependent and nondependent animals. At the same time point of withdrawal, there was a decrease in CRF immunoreactivity within the CeA, suggesting an increased extracellular release of CRF during withdrawal. There was no change in CRF immunoreactivity in the BNST or NAcSh. These results indicate that CRF, specifically within the CeA, plays a role in mediating excessive ethanol consumption in ethanol-dependent animals.
Epithelial–mesenchymal transition in breast cancer lines is mediated through PDGF‐D released by tissue‐resident stem cells

Epithelial–mesenchymal transition (EMT) generates tumor cells with stem cell properties. The aim of our study was to investigate the effects of adipose tissue‐derived stem cells (ASCs) on EMT of cancer cells and to further investigate the mechanisms involved. We demonstrate that conditioned medium from ASCs induces breast cancer cells (4T1) to express mesenchymal markers such as fibronectin, alpha smooth muscle actin and vimentin. Flow cytometry analyses show that ASC‐conditioned medium promotes the expansion of CD44high/CD24low cancer stem cells. Soft agar assays using T47D, BT474 and MCF‐7 breast cancer cells reveals that ASC conditioned medium promotes the anchorage‐independent growth of cancer cells. These effects were inhibited by a neutralizing antibody against platelet‐derived growth factor‐D (PDGF‐D). Furthermore, PDGF‐D treated breast cancer cells grow faster in a mouse model, and this effect could be neutralized by a PDGF antibody. In conclusion, our data show that tissue‐resident stem cells interact with the cancer microenvironment via PDGF‐D, induce EMT in the cancer cells in a paracrine fashion, thereby increasing the number of cancer stem cells and increase tumor growth in a PDGF dependent manner. Our findings shed new light on mechanisms where local tissue‐resident stem cells are able to promote the growth of breast cancer cells. Possibly this could open up a novel selective therapeutic strategy targeting EMT pathways and the specific communication between tissue‐resident normal stem cell and cancer stem cells, assuming that the blockage of PDGF‐D pathways is critical for tumor growth but would not affect normal tissue homeostasis.
A protein-RNA interaction network facilitates the template-independent cooperative assembly on RNA polymerase of a stable antitermination complex containing the lambda N protein.

The stable association of the N gene transcriptional antiterminator protein of bacteriophage lambda with transcribing RNA polymerase requires a nut site (boxA+boxB) in the nascent transcript and the Escherichia coli factors NusA, NusB, NusG, and ribosomal protein S10. We have used electrophoretic mobility shift assays to analyze the assembly of N protein, the E. coli factors, and RNA polymerase onto the nut site RNA in the absence of a DNA template. We show that N binds boxB RNA and that subsequent association of NusA with the N-nut site complex is facilitated by both boxA and boxB. In the presence of N, NusA, and RNA polymerase the nut site assembles ribonucleoprotein complexes containing NusB, NusG, and S10. The effects on assembly of mutations in boxA, boxB, NusA, and RNA polymerase define multiple weak protein-protein and protein-RNA interactions (e.g., NusB with NusG; NusA with boxB; NusA, NusB, and NusG with boxA) that contribute to the overall stability of the complex. Interaction of each component of the complex with two or more other components can explain the many observed cooperative binding associations in the DNA-independent assembly of a stable antitermination complex on RNA polymerase.
Coupled activation of the donor and the acceptor side of photosystem II during photoactivation of the oxygen evolving cluster.

Photoactivation of photosystem II has been studied in the FUD 39 mutant of Chlamydomonas reinhardtii that lacks the 23 kDa extrinsic subunit of photosystem II. We have taken advantage of the slow photoactivation rate of FUD 39, earlier demonstrated in Rova, E. M. , et al. [(1996) J. Biol. Chem. 271, 28918-28924], to study events in photosystem II during intermediate stages of the process. By measuring the EPR multiline signal, the decay of the variable fluorescence after single flashes, and electron transfer from water to the QB site, we found a good correlation between the building of a tetrameric Mn cluster, longer recombination times between QA- and the donor side of photosystem II, and the achievement of water splitting ability. An increased rate of electron transfer from QA- to the QB site on the acceptor side of photosystem II, mainly due to enhanced efficiency of binding of QB to its site, was found to precede the building of the Mn cluster. We also showed that TyrD was oxidized simultaneously with this increase in electron-transfer rate. Thus, it appears that photoactivation is sequential, with an increased rate of electron transfer on the acceptor side occurring together with the oxidation of TyrD in the first step, followed by the assembly of the Mn cluster. We suggest that a conformational change of photosystem II is induced early in the photoactivation process facilitating electron transfer from the primary donor to the acceptor side. As a consequence, TyrD, an auxiliary electron donor to P680+/TyrZ*, is oxidized. That this occurs before the Mn cluster is fully functional serves to protect photosystem II against donor side induced photodamage.
DNA VACCINATION OF BISON TO BRUCELLAR ANTIGENS ELICITS ELEVATED ANTIBODY AND IFN-γ RESPONSES

Brucella abortus remains a threat to the health and well-being of livestock in states bordering the Greater Yellowstone Area. During the past several years, cohabitation of infected wildlife with cattle has jeopardized the brucellosis-free status of Idaho, USA; Wyoming, USA; and Montana, USA. Current livestock B. abortus vaccines have not proven to be efficacious in bison (Bison bison) or elk (Cervus elaphus nelsoni). One problem with the lack of vaccine efficacy may stem from the failure to understand wildlife immune responses to vaccines. In an attempt to understand their immune responses, bison were vaccinated with eukaryotic DNA expression vectors encoding the Brucella periplasmic protein, bp26, and the chaperone protein, trigger factor (TF). These DNA vaccines have previously been shown to be protective against Brucella infection in mice. Bison were immunized intramuscularly at weeks 0, 2, and 4 with bp26 and TF DNA vaccines plus CpG adjuvant or empty vector (control) plus CpG. Blood samples were collected before vaccination and at 8, 10, and 12 wk after primary vaccination. The results showed that bison immunized with bp26 and TF DNA vaccines developed enhanced antibody, proliferative T cell, and interferon-gamma (IFN-γ) responses upon in vitro restimulation with purified recombinant bp26 or TF antigens, unlike bison immunized with empty vector. Flow cytometric analysis revealed that the percentages of CD4+ and CD8+ T lymphocytes from the DNA-vaccinated groups were significantly greater than they were for those bison given empty vector. These data suggest that DNA vaccination of bison may elicit strong cellular immune responses and serve as an alternative for vaccination of bison for brucellosis.
A STUDY TO DETERMINE THE CHARACTERISTICS OF GENERATION Y IN TURKEY: A SURVEY ON SCHOOL ADMINISTRATORS

ÖZ Bu çalışmada Türkiye‟de Y kuşağının nasıl tanımlandığı araştırılmaktadır. Yapılan literatür taramasında, Türkiye‟deki Y kuşağını tanımlamak için genellikle yurtdışı çalışmaların referans alındığı ve yurtdışında geliştirilen ölçeklerin kullanıldığı tespit edilmiştir. Araştırmada Türkiye‟deki Y kuşağının özelliklerini belirlemek amacıyla Ekşili ve Antalyalı (2016) tarafından geliştirilen dört boyuttan oluşan “Türkiye‟de Y Kuşağı Algısı Ölçeği” kullanılmıştır. Ölçek Y kuşağı ile yakın iletişim halinde olan lise yöneticilerine uygulanmıştır. Antalya ili merkez ilçelerini kapsayan araştırmanın analizleri 211 anket ile yapılmıştır. Sonuçta okul yöneticilerinin Y kuşağını yoğun teknoloji kullanan, orta düzeyde proaktif, yüksek düzeyde depresif benmerkezci olmakla birlikte yüksek düzeyde sosyal bir yapıya sahip bireyler olarak tanımladıkları ortaya çıkmıştır. Bu sonuçlar, proaktiflik ve depresif benmerkezcilik noktasında Türkiye‟deki Y kuşağı özelliklerinin yabancı akranlarından farklılaştığını göstermektedir. Anahtar Kelimeler: Kuşaklar, Y Kuşağı, Türkiye‟de Y Kuşağı, Kültürlerarası Farklılaşma, Lise Yöneticileri
Variable Transcriptional Activity of Endogenous Retroviruses in Human Breast Cancer

ABSTRACT Human endogenous retroviruses (HERVs) account for up to 9% of the human genome and include more than 800 elements related to betaretroviruses. While mouse mammary tumor virus (MMTV) is the accepted etiological agent of mammary tumors in mice, the role of retroviral elements in human breast cancer remains elusive. Here, we performed a comprehensive microarray-based analysis of overall retroviral transcriptional activities in 46 mammary gland tissue specimens representing pairs of nonmalignant and tumor samples from 23 patients. An analysis of nonmalignant tissue samples revealed a distinct, mammary gland-specific HERV expression profile that consists of 18 constitutively active HERV taxa. For corresponding tumor samples, a general trend toward lower levels of HERV transcription was observed, suggesting common regulatory mechanisms. In various subsets of patients, however, increased transcript levels of single class I HERV families (HERV-T, HERV-E, and HERV-F) and several class II families, including HML-6, were detected. An analysis of transcribed HML-6 sequences revealed either the activation of some or the increased activity of several proviral loci. No evidence for MMTV or human MMTV-like virus transcripts was found, indicating that transcriptionally active, MMTV analogous, exogenous viruses were not present in the breast cancer samples analyzed.
Involvement of Clp protease activity in modulating the Bacillus subtilisσW stress response

The induction of Bacillus subtilis genes controlled by the extracytoplasmic function alternative sigma factor σW is strongly impaired in a strain deleted for the ClpP peptidase gene and in a double knockout of the ClpX and ClpE ATPase genes. Truncated soluble forms of the σW anti‐sigma factor RsiW are stabilized in a clpP minus strain as revealed by the green fluorescent reporter protein fused to the N‐terminus of RsiW and by pulse‐chase experiments. Conserved alanine residues are present in the transmembrane region of RsiW, and mutations in these positions abolish induction of σW‐controlled genes. Following alkaline shock, a truncated cytoplasmic form of RsiW is detectable in a strain expressing a triple alanine mutant allele of rsiW. These data point to a mechanism where the trans‐membrane segment of RsiW contains a cryptic proteolytic tag that is uncovered as a result of intramembrane proteolysis of RsiW by RasP (YluC). After RasP‐clipped RsiW is detached from the membrane, this proteolytic tag becomes crucial for the complete degradation of RsiW by cytoplasmic proteases and the release of σW. ClpXP plays a major role in this third proteolytic step of stress‐induced degradation of RsiW. Overexpression of SsrA‐tagged green fluorescent protein as a ClpXP substrate protein reduces alkali induction of a σW‐controlled gene by a factor of about three, indicating that a titration mechanism is able to tune the σW‐mediated stress response to the cellular state.
Withdrawing low risk women from cervical screening programmes: mathematical modelling study.

Abstract Objective: To evaluate the impact of policies for removing women before the recommended age of 64 from screening programmes for cervical cancer in the United Kingdom. Design: A mathematical model of the clinical course of precancerous lesions which accounts for the influence of infection with the human papillomavirus, the effects of screening on the progression of disease, and the accuracy of the testing procedures. Two policies are compared: one in which women are withdrawn from the programme if their current smear is negative and they have a recent history of regular, negative results and one in which women are withdrawn if their current smear test is negative and a simultaneous test is negative for exposure to high risk types of human papillomavirus. Setting: United Kingdom cervical screening programme. Main outcome measures: The incidence of invasive cervical cancer and the use of resources. Results: Early withdrawal of selected women from the programme is predicted to give rise to resource savings of up to 25% for smear tests and 18% for colposcopies when withdrawal occurs from age 50, the youngest age considered in the study. An increase in the incidence of invasive cervical cancer, by up to 2 cases/100 000 women each year is predicted. Testing for human papillomavirus infection to determine which women should be withdrawn from the programme makes little difference to outcome. Conclusions: This model systematically analyses the consequences of screening options using available data and the clinical course of precancerous lesions. If further audit studies confirm the model's forecasts, a policy of early withdrawal might be considered. This would be likely to release substantial resources which could be channelled into other aspects of health care or may be more effectively used within the cervical screening programme to counteract the possible increase in cancer incidence that early withdrawal might bring.
Taming Nationalism? Political Community Building in the Post-Soviet Baltic States

Contents: Introduction Post-Soviet Baltic nationalisms in theories and case studies Nation building or nation killing? Experiencing and remembering Soviet population policies Post-Soviet Estonia: from restoration to integration? Post-Soviet Latvia: minority rights and the majority's insecurity Post-Soviet Lithuania: pragmatic inclusiveness and fear of uncertain loyalty Remembering the "Soviet Genocide" in the Independent Baltic States Conclusion Bibliography Index.
A fault-tolerant protocol for providing the exactly-once property of mobile agents

Mobile agent technology has been proposed for various fault-sensitive application areas, including electronic commerce, systems management and active messaging. Due to the autonomy of mobile agents, there is no natural instance that monitors the progress of an agent's execution. As a result, agents may be lost or blocked due to node crashes or network partitioning even if there are other nodes available that could continue processing. In this paper, we describe a protocol that provides exactly-once semantics of agent execution and additionally reduces the blocking probability of agents by introducing observer nodes for monitoring the progress of agents. This protocol is based on conventional transactional technology such as defined by X/Open DTP or CORBA OTS. It is being implemented in Mole, a mobile agent system developed at Stuttgart University.