Miracle-dz/UniFAR-FTUs huggingface dataset:
An APOBEC3 Mutational Signature in the Genomes of Human-Infecting Orthopoxviruses

Analysis of the viral lineages responsible for the 2022 monkeypox outbreak suggested that APOBEC enzymes are driving hMPXV1 evolution. Using 1,624 public sequences, we analyzed the mutations that accumulated between 2017 and the emergence of the predominant variant and those that characterize the last outbreak. ABSTRACT The ongoing worldwide monkeypox outbreak is caused by viral lineages (globally referred to as hMPXV1) that are related to but distinct from clade IIb MPXV viruses transmitted within Nigeria. Analysis of the genetic differences has indicated that APOBEC-mediated editing might be responsible for the unexpectedly high number of mutations observed in hMPXV1 genomes. Here, using 1,624 publicly available hMPXV1 sequences, we analyzed the mutations that accrued between 2017 and the emergence of the current predominant variant (B.1), as well as those that that have been accumulating during the 2022 outbreak. We confirmed an overwhelming prevalence of C-to-T and G-to-A mutations, with a sequence context (5′-TC-3′) consistent with the preferences of several human APOBEC3 enzymes. We also found that mutations preferentially occur in highly expressed viral genes, although no transcriptional asymmetry was observed. A comparison of the mutation spectrum and context was also performed against the human-specific variola virus (VARV) and the zoonotic cowpox virus (CPXV), as well as fowlpox virus (FWPV). The results indicated that in VARV genomes, C-to-T and G-to-A changes were more common than the opposite substitutions, although the effect was less marked than for hMPXV1. Conversely, no preference toward C-to-T and G-to-A changes was observed in CPXV and FWPV. Consistently, the sequence context of C-to-T changes confirmed a preference for a T in the −1 position for VARV, but not for CPXV or FWPV. Overall, our results strongly support the view that, irrespective of the transmission route, orthopoxviruses infecting humans are edited by the host APOBEC3 enzymes. IMPORTANCE Analysis of the viral lineages responsible for the 2022 monkeypox outbreak suggested that APOBEC enzymes are driving hMPXV1 evolution. Using 1,624 public sequences, we analyzed the mutations that accumulated between 2017 and the emergence of the predominant variant and those that characterize the last outbreak. We found that the mutation spectrum of hMPXV1 has been dominated by TC-to-TT and GA-to-AA changes, consistent with the editing activity of human APOBEC3 proteins. We also found that mutations preferentially affect highly expressed viral genes, possibly because transcription exposes single-stranded DNA (ssDNA), a target of APOBEC3 editing. Notably, analysis of the human-specific variola virus (VARV) and the zoonotic cowpox virus (CPXV) indicated that in VARV genomes, TC-to-TT and GA-to-AA changes are likewise extremely frequent. Conversely, no preference toward TC-to-TT and GA-to-AA changes is observed in CPXV. These results suggest that APOBEC3 proteins have an impact on the evolution of different human-infecting orthopoxviruses.
Recent Advances in Rotational Seismology

Rotational seismology is an emerging field of study concerned with all aspects of rotational motions induced by earthquakes, explosions, and ambient vibrations. Two recent monographs (Teisseyre et al. 2006; Teisseyre et al. 2008) and a Bulletin of the Seismological Society of America special issue on Rotational Seismology and Engineering Applications (Lee, Celebi et al. 2009) are useful starting points. Rotational seismology is of interest to a wide range of disciplines, including various branches of seismology, earthquake engineering, and geodesy, as well as to physicists using Earth-based observatories for detecting gravitational waves generated by astronomical sources, as predicted by Einstein in 1916. Traditionally, only translational ground motions are observed in seismology. However, we should also measure the three components of rotational motion and the six or more components of strain (Lee, Celebi et al. 2009). We will improve our understanding of the earthquake process (and the complex ground motions it generates) by developing new processing and inversion schemes including the new observables in rotations and strains. In this article we provide a summary of recent activities, some background information, and selected highlights of advances in rotational seismology and engineering applications. Following Hudnut (2005) on integrating real-time GPS with inertial sensors (including both translation and rotational), W. H. K. Lee (with K. W. Hudnut and J. R. Evans as coordinators) organized a mini-workshop on rotational seismology on February 16, 2006 (Evans et al. 2007). After the workshop, Evans and Lee contacted other groups active in rotational motions in several countries. An international working group on rotational seismology (IWGoRS) was then organized to promote investigations of rotational motions and their implications and to share experience, data, software, and results in an open Web-based environment (Todorovska et al. 2008). Anyone can join IWGoRS at http://www.rotational-seismology.org, subscribe to the mailing list, and contribute …
Priming effects of a slot machine game and amphetamine on probabilistic risk-taking in people with gambling disorder and healthy controls

ABSTRACT Introduction The Game of Dice Task (GDT) captures probabilistic risk-taking, which is an important feature of addictions and integral to gambling disorder (GD). No research appears to have assessed effects of gambling-specific priming manipulations or the pharmacological basis of such effects on the GDT. Aims To investigate effects of slot machine gambling (Slots) and d-amphetamine (AMPH; 20 mg) on risk-taking in people with GD and healthy controls (HCs) (n = 30/group). The role of dopamine (DA) was assessed by pre-treating participants with the D2 receptor (D2R)-preferring antagonist, haloperidol (HAL; 3-mg) or mixed D1R-D2R antagonist, fluphenazine (FLU; 3-mg). Hypotheses Slots and AMPH will each increase risk-taking based on fewer (less probable) possible outcomes selected (POS) and poorer net monetary outcomes (NMO; gains minus losses) on the GDT, with stronger effects in Group GD. If DA mediates these effects, outcomes will vary with pre-treatment. Method Participants attended a pre-experimental baseline session and 4 test sessions. Antagonist Group (HAL, FLU) was manipulated between-participants. Pre-treatment (antagonist, placebo) was manipulated within-participants and counterbalanced over sessions for Slots and AMPH test phases. Moderator/mediator effects of trait and neuropsychological factors and GD severity (South Oaks Gambling Screen; SOGS) were explored via covariance. Results AMPH led to an escalation in risky POS over trial blocks in both groups, regardless of pre-treatment. Cognitive inflexibility (high perseveration-proneness) moderated this effect in Group HC. In Group GD, SOGS selectively predicted riskier POS on AMPH sessions. Group GD achieved poorer NMO vs. Group HC on the pre-experimental baseline and Placebo-Slots sessions. Group HC selectively displayed poorer NMO on the Antagonist-Slots session. Conclusions The GDT can detect behavioral and pharmacological priming effects. Cognitive inflexibility and symptom severity moderate AMPH-induced risk-taking in HC and GD participants, respectively. Sensitization-related “wanting” of risk may contribute to the latter effect in people with GD.
Prognostic factors of overall and prostate‐specific antigen‐progression‐free survival in metastatic castration‐resistant prostate cancer patients treated with 177Lu‐PSMA‐617. A single‐center prospective observational study

Metastatic castration‐resistant prostate cancer (mCRPC) is characterized by heterogeneity among patients as well as therapy responses due to diverse genetic, epigenetic differences, and resistance mechanisms. At this stage of the disease, therapy modalities should be individualized in light of the patients' clinical state, symptoms, and genetic characteristics. In this prospective study, we aimed to evaluate the outcome of patients with mCRPC treated with 177Lutetium labeled PSMA‐617 therapy (PSMA‐RLT), as well as baseline and therapy‐related parameters associated with survival.
Interaction of the Monsoon and Pacific Trade Wind System at Interannual Time Scales Part I: The Equatorial Zone

Abstract The time history of the Monsoon System over the Indian Ocean has been developed from ship observations and merged with the Wyrtki-Meyers Pacific Trade Wind field. The interaction of these two massive wind systems has been studied by a rather new empirical orthogonal function (EOF) analysis capable of detecting propagating features in the wind systems. The current study (Part I) was confined to variations within ±10° of the equator. Results show the two wind systems are strongly coupled at interannual time scales. The coupling is effected through cyclostationary pulsations and longitudinal shifts of the huge surface convergence over Indonesia. The interaction may also he thought of as the spatial expansion/contraction of the wind systems. These changes can be viewed as the transition of the Monsoon/Trade Winds between two preferred climate states. One sub-element of this apparent bimodality in the wind fields is the El Nino phenomenon. The zonal component of the combined wind fields seems to insti.
Ion densities and magnetic signatures of dust pickup at Enceladus

Encedalus' plume of charged dust has been shown to strongly modify the plasma structures. Therefore, we analyze the magnetic signatures of dust to constrain the dust plume. For the first time, the mutual feedback between the nanograins and their plasma environment is investigated. Our model combines plasma simulations by means of the A.I.K.E. F. (Adaptive Ion‐Kinetic Electron‐Fluid) code with Monte Carlo simulations of the 3‐D profiles of the gas and dust plumes. Data from several instruments of Cassini are considered: the neutral plume model is in good agreement with INMS data, whereas theoretical predictions of the peak ion density are compared against CAPS data, and properties of the dust are obtained by comparing our results with MAG data from the recent E14–E19 flybys. Our main results are (1) due to the ion‐neutral chemistry, H3O+ is the predominant ion species within the plume; (2) the high nanograin densities observed by CAPS require an increased effective ionization frequency to fulfill quasi‐neutrality; (3) the nanograin pickup current makes only a minor contribution to the current systems; i.e., the major contribution of the dust arises from electron absorption; (4) the pickup of nanograins is clearly visible in the magnetic field signatures, even including the distant encounter E15; (5) MAG data indicate a southward extension of the charged dust plume of at least 4 Enceladus radii; (6) the modification of the currents by the nanograins is responsible for the surprising fact that Cassini did not detect a region with a reduced magnetic field strength.
Tropical Transition of an Unnamed, High-Latitude, Tropical Cyclone over the Eastern North Pacific

AbstractIn early November 2006, an unnamed tropical cyclone (TC) formed via the tropical transition (TT) process at 42°N over the eastern North Pacific. An extratropical cyclone (EC), developing downstream of a thinning upper-tropospheric trough over the eastern North Pacific, served as the precursor disturbance that would ultimately undergo TT. The TT of the unnamed TC was extremely unusual—occurring over ~16°C sea surface temperatures in a portion of the eastern North Pacific basin historically devoid of TC activity.This paper 1) identifies the upper- and lower-tropospheric features linked to the formation of the EC that transitions into the unnamed TC, 2) provides a synoptic overview of the features and processes associated with the unnamed TC’s TT, and 3) discusses the landfall of the weakening cyclone along the west coast of North America. As observed in previous studies of TT, the precursor EC progresses through the life cycle of a marine extratropical frontal cyclone, developing a bent-back warm fr.
“Stabilise-reduce, stabilise-reduce”: A survey of the common practices of deprescribing services and recommendations for future services

Background Public Health England recently called for the establishment of services to help people to safely stop prescribed drugs associated with dependence and withdrawal, including benzodiazepines, z-drugs, antidepressants, gabapentinoids and opioids. NICE identified a lack of knowledge about the best model for such service delivery. Therefore, we performed a global survey of existing deprescribing services to identify common practices and inform service development. Methods We identified existing deprescribing services and interviewed key personnel in these services using an interview co-produced with researchers with lived experience of withdrawal. We summarised the common practices of the services and analysed the interviews using a rapid form of qualitative framework analysis. Results Thirteen deprescribing services were included (8 UK, 5 from other countries). The common practices in the services were: gradual tapering of medications often over more than a year, and reductions made in a broadly hyperbolic manner (smaller reductions as total dose became lower). Reductions were individualised so that withdrawal symptoms remained tolerable, with the patient leading this decision-making in most services. Support and reassurance were provided throughout the process, sometimes by means of telephone support lines. Psychosocial support for the management of underlying conditions (e.g. CBT, counselling) were provided by the service or through referral. Lived experience was often embedded in services through founders, hiring criteria, peer support and sources of information to guide tapering. Conclusion We found many common practices across existing deprescribing services around the world. We suggest that these ingredients are included in commissioning guidance of future services and suggest directions for further research to clarify best practice.
Comparison between laparoscopic and abdominal radical hysterectomy for cervical adenosquamous carcinoma at stage IA2 to IIA2: A multicenter retrospective study

We aimed to compare the 5‐year oncological outcomes of laparoscopic/abdominal radical hysterectomy (LRH/ARH) in patients with cervical adenosquamous carcinoma at stage IA2 to IIA2 based on the 2009 or 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria.
Heterogeneous brain dynamic functional connectivity patterns in first‐episode drug‐naive patients with major depressive disorder

It remains challenging to identify depression accurately due to its biological heterogeneity. As people suffering from depression are associated with functional brain network alterations, we investigated subtypes of patients with first‐episode drug‐naive (FEDN) depression based on brain network characteristics. This study included data from 91 FEDN patients and 91 matched healthy individuals obtained from the International Big‐Data Center for Depression Research. Twenty large‐scale functional connectivity networks were computed using group information guided independent component analysis. A multivariate unsupervised normative modeling method was used to identify subtypes of FEDN and their associated networks, focusing on individual‐level variability among the patients for quantifying deviations of their brain networks from the normative range. Two patient subtypes were identified with distinctive abnormal functional network patterns, consisting of 10 informative connectivity networks, including the default mode network and frontoparietal network. 16% of patients belonged to subtype I with larger extreme deviations from the normal range and shorter illness duration, while 84% belonged to subtype II with weaker extreme deviations and longer illness duration. Moreover, the structural changes in subtype II patients were more complex than the subtype I patients. Compared with healthy controls, both increased and decreased gray matter (GM) abnormalities were identified in widely distributed brain regions in subtype II patients. In contrast, most abnormalities were decreased GM in subtype I. The informative functional network connectivity patterns gleaned from the imaging data can facilitate the accurate identification of FEDN‐MDD subtypes and their associated neurobiological heterogeneity.
Fostering Positive Views About Older Workers and Reducing Age Discrimination: A Retest of the Workplace Intergenerational Contact and Knowledge Sharing Model

Ageism toward older workers is prevalent in the labor market. The present study aimed to understand psychosocial mechanisms that may counteract this form of discrimination and help retain workers in the labor force. Using a sample of 500 Canadian younger and older workers, this study tested a model hypothesizing that intergenerational contacts and knowledge sharing practices can reduce ageist views about older adults and age-based discrimination against one’s own group, and in turn, enhance work engagement and intentions to remain in the workplace. The final model shows that knowledge sharing practices mediate the relationship between intergroup contacts and positive views about older workers as well as age-based discrimination. It also suggests that low levels of age-based discrimination increase work engagement and intentions to remain in the organization for workers of all ages. Practice and policy implications are discussed.
Mortality estimates and excess mortality in rheumatoid arthritis

Abstract Objectives To determine long-term (20 year) survival in RA patients enrolled in the Australian Rheumatology Association Database (ARAD). Methods ARAD patients with RA and data linkage consent who were diagnosed from 1995 onwards were included. Death data were obtained through linkage to the Australian National Death Index. Results were compared with age-, gender- and calendar year–matched Australian population mortality rates. Analysis included both the standardized mortality ratio (SMR) and relative survival models. Restricted mean survival time (RMST) at 20 years was calculated as a measure of life lost. Cause-specific SMRs (CS-SMRs) were estimated for International Classification of Diseases, Tenth Revision cause of death classifications. Results A total of 1895 RA patients were included; 74% were female, baseline median age 50 years (interquartile range 41–58), with 204 deaths. There was no increase in mortality over the first 10 years of follow up, but at 20 years the SMR was 1.49 (95% CI 1.30, 1.71) and the relative survival was 94% (95% CI 91, 97). The difference between observed (18.41 years) and expected (18.68 years) RMST was 4 months. Respiratory conditions were an important underlying cause of death in RA, primarily attributable to pneumonia [CS-SMR 5.2 (95% CI 2.3, 10.3)] and interstitial lung disease [CS-SMR 7.6 (95% CI 3.0, 14.7)], however, coronary heart disease [CS-SMR 0.82 (95% CI 0.42, 1.4)] and neoplasms [CS-SMR 1.2 (95% CI 0.89, 1.5)] were not. Conclusion Mortality risk in this RA cohort accrues over time and is moderately increased at 20 years of follow-up. Respiratory diseases may have supplanted cardiovascular diseases as a major contributor to this mortality gap.
Women’s attitudes about combined hormonal contraception (CHC) - induced menstrual bleeding changes - influence of personality traits in an Italian clinical sample

Abstract Objectives We investigated the attitudes to change the frequency of menstrual bleeding by using combined hormonal contraception (CHC). Personality characteristics were also explored. Methods We conducted a cross-sectional study in two university hospitals in northern Italy. Current, past and never CHC users (n = 545; age 18–44 years) completed a self-administered semi-structured questionnaire and the Ten-Item Personality Inventory (TIPI). Results Forty-five percent of responders (n = 301) would prefer to change their bleeding frequency by using CHC. A flexible regimen was the preferred choice (n = 80; 33%) followed by extended regimens to bleed every 3 months (n = 54; 22%) or to never bleed (n = 43; 18%). The main positive reasons were to avoid dysmenorrhea (43%) and have more freedom in sexual (36%) and active (35%) life, whereas the main reason for a negative attitude was ‘menstrual rhythm is natural’ (59%). Age had a significant influence on women’s willingness to change menstrual frequency by using CHC [>39 years (57%), 30–39 years (31%) and <30 years (46%)] (χ2: 9.1; p = 0.01). Never users significantly reported a more negative attitude (71%) in comparison with past (51%) and current users (49%) (χ2: 18.7; p = 0.001). Personality traits played a role, with higher scores of openness (p = 0.005) and extraversion (p = 0.001) in women with a positive attitude. Conclusions Almost half of our study sample reported a preference for changing their menstrual pattern by using CHC. Flexibility was the preferred choice across age and use of CHC. Personality characteristics (openness and extroversion) might influence attitudes toward CHC-induced menstrual bleeding changes.
Utility of Abbreviated Small Bowel Follow Through Study in the Management of Small Bowel Obstruction

Introduction Small bowel obstruction is a common surgical complaint. Most small bowel obstructions are managed successfully nonoperatively. Unanimous guidelines for nonoperative management of small bowel obstruction do not exist. Methods A standardized protocol for water-soluble contrast administration and abbreviated small bowel follow through imaging was implemented in January of 2021. A retrospective chart review identified 111 patients admitted for SBO from 6/2019 to 9/2019 for a control group. A planned follow-up review identified 158 patients managed according to the new protocol from 3/2021 to 10/2021. The primary outcome was in-hospital length of stay. Standard statistical analyses were performed and pre-specified. Results Before implementation of the standardized protocol patients that were managed strictly nonoperatively, the mean length of stay (LOS) was 8.3 days. After implementation, the average LOS was 4.8 (P < .0001). Comparatively, patients admitted after protocol implementation were more likely to undergo CT scan with PO contrast on admission (98.1% vs 90.1%; P < .005), undergo NG tube decompression (84.7% vs 68.5%; P < .005), and undergo water-soluble contrast with abbreviated or formal SBFT (75.3% vs 37.8%; P < .0001). Conclusion Implementation of a standardized protocol utilizing abbreviated SBFT with water-soluble contrast for the management of SBO at our institution resulted in a decrease in the average length of stay for patients definitively managed in a nonoperative fashion.
Majorization and the Birthday Inequality

which is greater than 0.5 even if there are only 23 people in the room. Probability instructors are fond of demonstrating this fact in class by asking the students to announce their birthdays until a match is discovered. The authors are courageous enough to try the demonstration in classes with 30 or more students so that the probability of a match is at least 0.706. Recently, however, we got worried. The probabilities given above are based on the assumption that a randomly chosen individual is just as likely to have a birthday on, say, October 1 as on January 10. In other words, the assumption is that