bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapport, Resistance, and Reactance
Authors: Alison Emily K. , Alison Laurence J. , Surmon-Böhr Frances , Shortland Neil D.
Published: November 2020

This chapter outlines the definition of and use of rapport, based on principles of humanistic psychology. While rapport has been recognized in countless studies as a key feature of successful interrogations, it has historically been poorly defined and operationalized. This chapter uses real-world examples to highlight what rapport is and what it is not. The chapter also highlights key concepts and strategies drawn from the motivational interviewing literature that can be successfully applied to an interrogation context. Specifically, the chapter discusses a form of interviewee resistance known as “reactance,” which can be created by an interviewer trying too hard to make someone talk.
ORBIT
Authors: Alison Laurence J. , Alison Emily K. , Surmon-Böhr Frances , Shortland Neil D.
Published: November 2020

This chapter provides a detailed overview of the Observing Rapport Based Interpersonal Techniques (ORBIT) model of interviewing and its principles. It discusses how ORBIT is unique in that it evolved out of analysis of the largest sample of real-world interrogations in the world. The authors explain how they gained access to the data and their approach to analysis and coding. The chapter then describes the ORBIT approach to building rapport and describes ORBIT’s interpersonal behavior model. It also outlines the other variables that make up the ORBIT coding framework, including their measure of detainee engagement and yield. It uses a real-world example of an interrogation with Colonel Russel Williams to show how the ORBIT model works in practice.
How to Build Rapport
Authors: Alison Laurence J. , Barrett-Pink Chloë , Surmon-Böhr Frances , Shortland Neil D. , Alison Emily K. , Christiansen Paul
Published: November 2020

This chapter examines the impact of the UK National Counter-Terrorism Training program (Alcyone). Alcyone is a 6-day course that provides the following: (1) psychological training in Observing Rapport Based Interpersonal Techniques (ORBIT), (2) input on pre-interview briefing, and (3) legislation and input on safety interviewing. Approximately 80% of the course involves scenario-based role-play with additional knowledge checks and short lecture inputs. The chapter details the analysis used to assess the program’s impact. Multivariate analysis of variance revealed that Alcyone-trained officers showed a significantly greater reliance on adaptive interpersonal skills that had been taught in the course and demonstrated significantly fewer maladaptive interpersonal behaviors that they had been taught to avoid. There was also a significant increase in the use of rapport-based behaviors and a greater extraction of information from the suspects. Although several other factors may also account for an increase in yield, the increase in all the aspects that these officers had been taught in the course provides support that the course had a positive impact. This has implications for interview training programs and for the dissemination of evidence-based practice for counterterrorism interviewing.
Regulatory Compliance of Health Warnings on Tobacco Packs in Karnataka, India
Authors: Mullapudi Somya , Kulkarni Muralidhar M , Kamath Veena G , Britton John , Moodie Crawford , Kamath Asha
Published: November 2020

Introduction

In September 2014, the Government of India introduced legislation requiring all tobacco packaging to display a health warning covering 85% (60% pictorial, 25% text) of the principal display area of the pack, of at least 4 cm in height and 3.5 cm width, with legible text in a white font on a black background and in English and/or the same Indian language as the language used on the pack. We evaluated compliance with this legislation in the Udupi district of Karnataka, India.

Methods

We procured one example of every tobacco pack of cigarettes, beedis, chewing tobacco, and snuff sold by a convenience sample of retailers in one urban and two rural areas in each of the five administrative blocks of the Udupi district between June and August 2018. For each pack we measured the size of the health warning, calculated the proportion of the pack covered, and assessed the legibility.

Results

A total of 365 packs were collected from retailers, with 357 of these branded and eight, all packs of snuff, unbranded. Warnings on 320 (87.3%) packs did not reach the legally required proportional magnitude, warnings on 140 (38.4%) packs were not legible, and warnings on 117 packs (32.1%) did not meet the language requirement. Only 45 packs (12.3%) were fully compliant.

Conclusions

Compliance with warning legislation in this district of India is low, highlighting the need for more effective enforcement.

Implications

Warnings on tobacco packaging are an important and inexpensive means of communicating the harms associated with tobacco use. However, relatively few studies have explored regulatory compliance with warnings. We collected all unique tobacco packs from 66 retailers in a district in Karnataka in India and assessed whether each met the legislative requirements in terms of warning size and proportion of the pack covered, legibility, and the language used. Of the 365 packs collected, only one in eight was compliant with the legislative requirements. This study highlights the importance of assessing warning compliance and the need for enforcement in India.
Risk of depression, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis: a multinational network cohort study
Authors: Lane Jennifer C E , Weaver James , Kostka Kristin , Duarte-Salles Talita , Abrahao Maria Tereza F , Alghoul Heba , Alser Osaid , Alshammari Thamir M , Areia Carlos , Biedermann Patricia , Banda Juan M , Burn Edward , Casajust Paula , Fister Kristina , Hardin Jill , Hester Laura , Hripcsak George , Kaas-Hansen Benjamin Skov , Khosla Sajan , Kolovos Spyros , Lynch Kristine E , Makadia Rupa , Mehta Paras P , Morales Daniel R , Morgan-Stewart Henry , Mosseveld Mees , Newby Danielle , Nyberg Fredrik , Ostropolets Anna , Woong Park Rae , Prats-Uribe Albert , Rao Gowtham A , Reich Christian , Rijnbeek Peter , Sena Anthony G , Shoaibi Azza , Spotnitz Matthew , Subbian Vignesh , Suchard Marc A , Vizcaya David , Wen Haini , Wilde Marcel de , Xie Junqing , You Seng Chan , Zhang Lin , Lovestone Simon , Ryan Patrick , Prieto-Alhambra Daniel ,   for the OHDSI-COVID-19 consortium
Published: November 2020

Objectives

Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA.

Methods

We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%.

Results

A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis.

Conclusion

HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation.

Trial registration

Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2.
Perturbations of the gut microbiome in anti-CCP positive individuals at risk of developing rheumatoid arthritis
Authors: Rooney Christopher M , Mankia Kulveer , Mitra Suparna , Moura Ines B , Emery Paul , Wilcox Mark H
Published: November 2020

Objective

Individuals with newly diagnosed RA have a distinct microbiome when compared with healthy controls. However, little is known as to when these microbiome perturbations begin. Using a prospective at-risk cohort of individuals positive for anti-citrullinated protein (anti-CCP) antibody with new onset musculoskeletal symptoms, but without clinical arthritis, we investigated for the presence of a gut dysbiosis before the onset of RA.

Methods

The gut microbiota of 25 anti-CCP positive individuals without clinical synovitis were sequenced targeting the V4 region of the 16S rRNA gene. Using a publicly available database, a control population of 44 individuals, approximately matched in age, gender, diet and ethnicity was selected for comparison, using the same sequencing methodology. Median interval between sample collection and progression to RA was 188 days. Taxonomic analysis was performed using QIIME and MEGAN, and statistical analysis using R software.

Results

There were significant differences (P =0.01) at family level in gut microbiomes of anti-CCP positive individuals vs controls. The anti-CCP positive population had an overabundance of Lachnospiraceae, Helicobacteraceae, Ruminococcaceae, Erysipelotrichaceae and Bifidobacteriaceae, among others. Five individuals progressed to RA between sample collection and analysis. Clustering of the progressor population was observed on a phylogenetic network created using a probabilistic similarity index (Goodall’s index).

Conclusions

Anti-CCP positive at-risk individuals without clinical synovitis appear to have a distinct gut microbiome compared with healthy controls. Phylogenetic clustering was observed in individuals who progressed to RA, suggesting that distinct taxa are associated with the development of RA many months before its onset.
Relationships between diuretic-related hyperuricemia and cardiovascular events: data from the URic acid Right for heArt Health study
Authors: Maloberti Alessandro , Bombelli Michele , Facchetti Rita , Barbagallo Carlo Maria , Bernardino Bruno , Rosei Enrico Agabiti , Casiglia Edoardo , Cicero Arrigo Francesco Giuseppe , Cirillo Massimo , Cirillo Pietro , Desideri Giovambattista , D’elia Lanfranco , Dell’Oro Raffaella , Ferri Claudio , Galletti Ferruccio , Giannattasio Cristina , Loreto Gesualdo , Iaccarino Guido , Lippa Luciano , Mallamaci Francesca , Masi Stefano , Mazza Alberto , Muiesan Maria Lorenza , Nazzaro Pietro , Parati Gianfranco , Palatini Paolo , Pauletto Paolo , Pontremoli Roberto , Quarti-Trevano Fosca , Rattazzi Marcello , Rivasi Giulia , Salvetti Massimo , Tikhonoff Valerie , Tocci Giuliano , Ungar Andrea , Verdecchia Paolo , Viazzi Francesca , Volpe Massimo , Virdis Agostino , Grassi Guido , Borghi Claudio
Published: November 2020

Objective:

Although the relationship between hyperuricemia and cardiovascular events has been extensively examined, data on the role of diuretic-related hyperuricemia are still scanty. The present study was designed to collect information on the relationship between diuretic-related hyperuricemia and cardiovascular events.

Methods:

The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, observational cohort study involving data on individuals recruited from all the Italy territory under the patronage of the Italian Society of Hypertension with an average follow-up period of 122.3 ± 66.9 months. Patients were classified into four groups according to the diuretic use (yes vs. no) and serum uric acid (SUA) levels (higher vs. lower than the median value of 4.8 mg/dl). All-cause death, cardiovascular deaths and first cardiovascular event were considered as outcomes.

Results:

Seventeen thousand, seven hundred and forty-seven individuals were included in the analysis. Mean age was 57.1 ± 15.2 years, men were 45.3% and SBP and DBP amounted to 144.1 ± 24.6 and 85.2 ± 13.2 mmHg. 17.2% of individuals take diuretics of whom 58% had SUA higher than median value. Patients with hyperuricemia without diuretic use served as reference group. In multivariate adjusted analysis (sex, age, SBP, BMI, glucose, total cholesterol, and glomerular filtration rate) individuals with hyperuricemia and diuretic use exhibit a similar risk for the three outcomes as compared with the reference group.

Conclusion:

Our study showed that diuretic-related hyperuricemia carry a similar risk of cardiovascular events and all-cause mortality when compared with individuals that present hyperuricemia in absence of diuretic therapy.
The HIPARCO-2 study: long-term effect of continuous positive airway pressure on blood pressure in patients with resistant hypertension: a multicenter prospective study
Authors: Navarro-Soriano Cristina , Torres Gerard , Barbé Ferrán , Sánchez-de-la-Torre Manuel , Mañas Pedro , Lloberes Patricia , Cambriles Trinidad Díaz , Somoza María , Masa Juan F. , González Mónica , Mañas Eva , de la Peña Mónica , García-Río Francisco , Montserrat Josep María , Muriel Alfonso , Oscullo Grace , García-Ortega Alberto , Posadas Tomás , Campos-Rodríguez Francisco , Martínez-García Miguel-Ángel
Published: November 2020

Introduction:

Short-term treatment with continuous positive airway pressure (CPAP) produces a clinically significant reduction in blood pressure (BP) in patients with obstructive sleep apnea (OSA) and resistant hypertension. However, it is unknown whether this effect continues over the long-term. Our objective was to assess the effect of long-term CPAP on BP in patients with OSA and resistant hypertension.

Methods:

The study included 161 patients diagnosed with both OSA [apnea--hypopnea index (AHI) ≥15] and resistant hypertension diagnosed via 24-hour ambulatory BP measurement (24-h ABPM), in whom a second analysis via 24-h ABPM was performed at the end of the follow-up.

Results:

Patients were followed up within 59 months [interquartile range (IQR): 44–70]. CPAP treatment was prescribed to 82% of the patients (70% with good adherence to CPAP defined as use of CPAP at least 4 h/night). A comparison between the adherent group and nonadherent group (including those with CPAP not prescribed) showed that CPAP adherents had a significant drop in the 24-h BP, both systolic [−3.9 mmHg; 95% confidence interval (CI): −8.1 to 0.3] and diastolic pressure (−3.5 mmHg [95% [CI]: −6.4–0.5]), with a higher magnitude during the night (−5.5 and −4.9 mmHg, respectively). The CPAP adherent group needed a mean of 1.1 less antihypertensive drugs (particularly spironolactone). Finally, there was a positive correlation between the drop in 24-h SBP and the hours of CPAP use (r = 0.24; P = 0.01).

Conclusion:

Good adherence to long-term CPAP treatment largely succeeded in significantly reducing BP in those patients with OSA and resistant hypertension, despite the use of a lower number of antihypertensive drugs.
Prevalence, awareness, treatment and control of hypertension in Greece: EMENO national epidemiological study
Authors: Stergiou George S. , Menti Ariadni , Kalpourtzi Natasa , Gavana Magda , Vantarakis Apostolos , Chlouverakis Grigoris , Hajichristodoulou Christos , Trypsianis Grigoris , Voulgari Paraskevi V. , Alamanos Yannis , Karakosta Argiro , Touloumi Giota
Published: November 2020

Objective:

The evidence on the epidemiology of hypertension in Greece is limited. The prevalence and control of hypertension was assessed in randomly selected adults of the general population in Greece within the nationwide epidemiological study EMENO.

Method:

On the basis of 2011 census, EMENO applied a multistage stratified random sampling method involving 577 areas throughout Greece (2013–2016). Participants were assessed at home visits with standardized questionnaires, blood tests and triplicate seated blood pressure (BP) measurements (validated upper-arm automated oscillometric device Microlife BPA100 Plus). Hypertension was defined as BP at least 140/90 mmHg (average of second--third measurement) and/or use of antihypertensive drugs. Sampling weights were applied for study design and post-stratification weights to match the age/sex distribution to the general population in Greece. Nonresponse was adjusted by inverse probability weighting.

Results:

A total of 6006 individuals were recruited and 4699 with valid data were analysed [mean (SD) age 49.2 (18.6) years, men 48.6%, BMI 28.2 (5.7) kg/m2]. The prevalence of hypertension was 39.6% and was higher in men than women (42.7 vs. 36.5%, P < 0.001). Among patients with hypertension, 31.8% were unaware (men/women 39.2/23.6%, P < 0.001), 2.7% aware but untreated (men/women 2.9/2.5%, P = NS), 35.1% treated uncontrolled (32.1/38.3%, P < 0.01) and 30.5% treated controlled (25.8/35.6%, P < 0.001).

Conclusion:

The prevalence of hypertension in Greece seems to be rising and affects 40% of the adults. One-third of them are undiagnosed and only 30% are controlled with treatment. Nationwide programmes are needed to prevent hypertension and improve its awareness and control aiming at reducing the rate cardiovascular diseases.
Predicting pain: differential pain thresholds during self-induced, externally induced, and imagined self-induced pressure pain
Authors: Lalouni Maria , Fust Jens , Vadenmark-Lundqvist Viktor , Ehrsson H. Henrik , Kilteni Konstantina , Birgitta Jensen Karin
Published: November 2020

During self-induced pain, a copy of the motor information from the body's own movement may help predict the painful sensation and cause downregulation of pain. This phenomenon, called sensory attenuation, enables the distinction between self-produced stimuli vs stimuli produced by others. Sensory attenuation has been shown to occur also during imagined self-produced movements, but this has not been investigated for painful sensations. In the current study, the pressure pain thresholds of 40 healthy participants aged 18 to 35 years were assessed when pain was induced by the experimenter (other), by themselves (self), or by the experimenter while imagining the pressure to be self-induced (imagery). The pressure pain was induced on the participants left lower thigh (quadriceps femoris) using a handheld algometer. Significant differences were found between all conditions: other and self (P < 0.001), other and imagery (P < 0.001), and self and imagery (P = 0.004). The mean pressure pain threshold for other was 521.49 kPa (SE = 38.48), for self 729.57 kPa (SE = 32.32), and for imagery 618.88 kPa (SE = 26.67). Thus, sensory attenuation did occur both in the self condition and the imagery condition. The results of this study may have clinical relevance for understanding the mechanisms involved in the elevated pain thresholds seen in patients with self-injury behavior and the low pain thresholds seen in patients with chronic pain conditions. Imagery of sensory attenuation might also be used to alleviate the pain experience for patients undergoing procedural pain.
Brain imaging signature of neuropathic pain phenotypes in small-fiber neuropathy: altered thalamic connectome and its associations with skin nerve degeneration
Authors: Chao Chi-Chao , Tseng Ming-Tsung , Lin Yea-Huey , Hsieh Paul-Chen , Lin Chien-Ho (Janice) , Huang Shin-Leh , Hsieh Sung-Tsang , Chiang Ming-Chang
Published: November 2020

Small-fiber neuropathy (SFN) has been traditionally considered as a pure disorder of the peripheral nervous system, characterized by neuropathic pain and degeneration of small-diameter nerve fibers in the skin. Previous functional magnetic resonance imaging studies revealed abnormal activations of pain networks, but the structural basis underlying such maladaptive functional alterations remains elusive. We applied diffusion tensor imaging to explore the influences of SFN on brain microstructures. Forty-one patients with pathology-proven SFN with reduced skin innervation were recruited. White matter connectivity with the thalamus as the seed was assessed using probabilistic tractography of diffusion tensor imaging. Patients with SFN had reduced thalamic connectivity with the insular cortex and the sensorimotor areas, including the postcentral and precentral gyri. Furthermore, the degree of skin nerve degeneration, measured by intraepidermal nerve fiber density, was associated with the reduction of connectivity between the thalamus and pain-related areas according to different neuropathic pain phenotypes, specifically, the frontal, cingulate, motor, and limbic areas for burning, electrical shocks, tingling, mechanical allodynia, and numbness. Despite altered white matter connectivity, there was no change in white matter integrity assessed with fractional anisotropy. Our findings indicate that alterations in structural connectivity may serve as a biomarker of maladaptive brain plasticity that contributes to neuropathic pain after peripheral nerve degeneration.
Mig6 decreases hepatic EGFR activation and survival during saturated fatty acid-induced endoplasmic reticulum stress
Authors: Lutkewitte Andrew J. , Chen Yi-Chun , Hansen Jeffrey L. , Fueger Patrick T.
Published: November 2020

Hyperlipidemia associated with obesity and type 2 diabetes (T2D) promotes excess hepatic lipid storage (steatosis) and endoplasmic reticulum (ER) stress, thereby reducing hepatic cell proliferation and survival. An important receptor tyrosine kinase controlling liver proliferation and survival is the epidermal growth factor receptor (EGFR). EGFR expression and activation are decreased during steatosis in humans and several animal models of obesity. Therefore, restoring EGFR activation in obesity-induced ER stress and diabetes could restore the liver’s capacity for survival and regeneration. As an inducible feedback inhibitor of EGFR activity, mitogen-inducible gene 6 (Mig6) is a novel target for enhancing EGFR signaling during diet-induced obesity (DIO) and T2D. Thus, we hypothesized hepatic ER stress induces Mig6 expression and decreases EGFR activation during DIO and diabetes. We identified that Mig6 expression was increased during obesity-induced insulin resistance in C57Bl/6J mice fed a high fat diet. We also discovered that both pharmacological- and fatty acid-driven ER stress increased Mig6 expression and decreased EGF-mediated EGFR activation in primary rat hepatocytes and cell lines. Furthermore, siRNA-mediated Mig6 knockdown restored EGFR signaling and reduced caspase 3/7 activation during ER stress. Therefore, we conclude Mig6 is increased during ER stress in DIO, thereby reducing EGFR activation and enhancing cell death. The implications are the induction of Mig6 during DIO and diabetes may decrease hepatocyte survival, thus hindering cellular repair and regenerative mechanisms.
Population history and the differential consequences of inbreeding and outcrossing in a plant metapoplation
Authors: Fields Peter D. , Arnold Gretchen , Kniskern Joel M. , Taylor Douglas R.
Published: November 2020

The phenotypic consequences of inbreeding typically result in a fitness decline proportional to the increase in the inbreeding coefficient,F. This basic assumption of a predictable, inverse relationship between fitness andFhas been questioned by a number of empirical studies. We explored the relationship between population history and inbreeding in a metapopulation of the plantSilene latifolia, for which long-term data are available for the historical size and spatial distribution of hundreds of local demes. We used a population genetic analysis to estimate gene flow and bi-parental inbreeding (FIS) in demes with different histories of spatial isolation. A controlled crossing experiment examined whether the effect of inbreeding and outcrossing on fitness-related traits varied with different histories of population size and isolation. Historically isolated demes experienced less gene flow and an increase inFIS, as well as significant inbreeding advantage and outbreeding depression for traits expressed early in life. The causes of variation in theF-fitness relationship among populations will include variance in the distribution of deleterious recessive alleles driven by aspects of population history, including population size, founder effects, gene flow, bi-parental inbreeding, and opportunities for the purging of genetic load. Our findings show that isolation and historical variation in population size likely contribute substantial variation in past inbreeding and the consequences of future inbreeding across the metapopulation.
distinct: a novel approach to differential distribution analyses
Authors: Tiberi Simone , Crowell Helena L , Samartsidis Pantelis , Weber Lukas M , Robinson Mark D
Published: November 2020

We presentdistinct, a general method for differential analysis of full distributions that is well suited to applications on single-cell data, such as single-cell RNA sequencing and high-dimensional flow or mass cytometry data. High-throughput single-cell data reveal an unprecedented view of cell identity and allow complex variations between conditions to be discovered; nonetheless, most methods for differential expression target differences in the mean and struggle to identify changes where the mean is only marginally affected.distinctis based on a hierarchical non-parametric permutation approach and, by comparing empirical cumulative distribution functions, identifies both differential patterns involving changes in the mean, as well as more subtle variations that do not involve the mean. We performed extensive bench-marks across both simulated and experimental datasets from single-cell RNA sequencing and mass cytometry data, wheredistinctshows favourable performance, identifies more differential patterns than competitors, and displays good control of false positive and false discovery rates.distinctis available as a Bioconductor R package.
Predicting direct and indirect non-target impacts of biocontrol agents using machine-learning approaches
Authors: Kotula Hannah J. , Peralta Guadalupe , Frost Carol M. , Todd Jacqui H. , Tylianakis Jason M.
Published: November 2020

Biological pest control (i.e. ‘biocontrol’) agents can have direct and indirect non-target impacts, and predicting these effects (especially indirect impacts) remains a central challenge in biocontrol risk assessment. The analysis of ecological networks offers a promising approach to understanding the community-wide impacts of biocontrol agents (via direct and indirect interactions). Independently, species traits and phylogenies have been shown to successfully predict species interactions and network structure (alleviating the need to collect quantitative interaction data), but whether these approaches can be combined to predict indirect impacts of natural enemies remains untested. Whether predictions of interactions (i.e. direct effects) can be made equally well for generalists vs. specialists and across different habitat types is also untested for consumer-prey interactions, though previous work on mutualist networks suggests that interactions among generalists may be more difficult to predict. Here, we used two machine learning techniques (random forest and k-nearest neighbour; KNN) to test whether we could accurately predict empirically-observed quantitative host-parasitoid networks using trait, abundance, and phylogenetic information. Then, we tested whether the accuracy of machine-learning-predicted interactions depended on the generality of the interacting partners or on the source (habitat type) of the training data. Finally, we used these predicted networks to generate predictions of indirect effects via shared natural enemies (i.e. apparent competition), and tested these predictions against empirically observed indirect effects between hosts. We found that random-forest models predicted host-parasitoid pairwise interactions (which could be used to predict attack of non-target host species) more successfully than KNN, and this predictive ability depended on the generality of the interacting partners, but not the source (habitat type) of data used to train the models. Further, although our machine-learning informed methods could significantly predict indirect effects, the explanatory power for both direct and indirect interactions was reasonably low. Combining machine-learning and network approaches provides a starting point for reducing risk in biocontrol.
Auxin requirements for a meristematic state in roots depend on a dual brassinosteroid function
Authors: Ackerman-Lavert M. , Fridman Y. , Matosevich R , Khandal H , Friedlander L. , Vragović K. , Ben El R. , Horev G. , Efroni I , Savaldi-Goldstein S.
Published: November 2020

The organization of the root meristem is maintained by a complex interplay between plant hormones signaling pathways that both interpret and determine their accumulation and distribution. Brassinosteroids (BR) and auxin signaling pathways control the number of meristematic cells in the Arabidopsis root, via an interaction that appears to involve contradicting molecular outcomes, with BR promoting auxin signaling input but also repressing its output. However, whether this seemingly incoherent effect is significant for meristem function is unclear. Here, we established that a dual effect of BR on auxin, with BR simultaneously promoting auxin biosynthesis and repressing auxin transcriptional output, is essential for meristem maintenance. Blocking BR-induced auxin synthesis resulted in rapid BR-mediated meristem loss. Conversely, plants with reduced BR levels were resistant to loss of auxin biosynthesis and these meristems maintained their normal morphology despite a 10-fold decrease in auxin levels. In agreement, injured root meristems which rely solely on local auxin synthesis, regenerated when both auxin and BR synthesis were inhibited. Use of BIN2 as a tool to selectively inhibit BR signaling, revealed meristems with distinct phenotypes depending on the perturbed tissue; meristem reminiscent of BR-deficient mutants or of high BR exposure. This enabled mapping BR-auxin interactions to the outer epidermis and lateral root cap tissues, and demonstrated the essentiality of BR signaling in these tissues for meristem maintenance. BR activity in internal tissues however, proved necessary to control BR homeostasis. Together, we demonstrate a basis for inter-tissue coordination and how a critical ratio between these hormones determines the meristematic state.
COUNTEN – an AI-driven tool for rapid, and objective structural analyses of the Enteric Nervous System
Authors: Kobayashi Yuta , Bukowski Alicia , Das Subhamoy , Espenel Cedric , Gomez-Frittelli Julieta , Wagle Narayani , Bakshi Shriya , Saha Monalee , Kaltschmidt Julia A. , Venkataraman Archana , Kulkarni Subhash
Published: November 2020

Healthy gastrointestinal functions require a healthy Enteric Nervous System (ENS). ENS health is often defined by the presence of normal ENS structure. However, we currently lack a comprehensive understanding of normal ENS structure as current methodologies of manual enumeration of neurons within tissue and ganglia can only parse limited tissue regions; and are prone to error, subjective bias, and peer-to-peer discordance. Thus, there is a need to craft objective methods and robust tools to capture and quantify enteric neurons over a large area of tissue and within multiple ganglia. Here, we report on the development of an AI-driven tool COUNTEN which parses HuC/D-immunolabeled adult murine myenteric ileal plexus tissues to enumerate and classify enteric neurons into ganglia in a rapid, robust, and objective manner. COUNTEN matches trained humans in identifying, enumerating and clustering myenteric neurons into ganglia but takes a fraction of the time, thus allowing for accurate and rapid analyses of a large tissue region. Using COUNTEN, we parsed thousands of myenteric neurons and clustered them in hundreds of myenteric ganglia to compute metrics that help define the normal structure of the adult murine ileal myenteric plexus. We have made COUNTEN freely and openly available to all researchers, to facilitate reproducible, robust, and objective measures of ENS structure across mouse models, experiments, and institutions.
Habituation and goal-directed arbitration mechanisms and failures under partial observability
Authors: Sánchez-Fibla Martí
Published: November 2020

Abstract

We often need to make decisions under incomplete information (partial observability) and the brain manages to add the right minimal context to the decision-making. Partial observability may also be handled by other mechanisms than adding contextual experience / memory. We propose that parallel and sequential arbitration of Habituation (Model-Free, MF) and Goal-Directed (Model-Based, MB) behavior may be at play to deal with partial observability “on-the-fly”, and that MB may be of different types (going beyond the MF/MB dichotomy [4]). To illustrate this, we identify, describe and model with Reinforcement Learning (RL) a behavioral anomaly (an habituation failure) occurring during the so-called Hotel Elevators Rows (HER, for short) task: a prototypical partial observation situation that can be reduced to the well studied Two and One Sequence Choice Tasks. The following hypothesis are supported by RL simulation results: (1) a parallel (semi)model-based successor representation mechanism is operative while learning to habituate which detects model-based mismatches and serves as an habituation surveillance, (2) a retrospective inference is triggered to identify the source of the habituation failure (3) a model-free mechanism can trigger model-based mechanisms in states in which habituation failed. The “failures” in the title refer to: the habituation failures that need to be monitored and surveilled (1) and to the failures that we identified in prototypical state of the art Model-Based algorithms (like DynaQ) when facing partial observability. As other research on MF/MB arbitration shows, the identification of these new mechanisms could shine light into new treatments for addiction, compulsive behavior (like compulsive checking) and understand better accidents caused by habituation behaviors.
Direct Observation of the Mechanism of Antibiotic Resistance by Mix-and-Inject at the European XFEL
Authors: Pandey Suraj , Calvey George , Katz Andrea M. , Malla Tek Narsingh , Koua Faisal H. M. , Martin-Garcia Jose M. , Poudyal Ishwor , Yang Jay-How , Vakili Mohammad , Yefanov Oleksandr , Zielinski Kara A. , Bajt Saša , Awel Salah , Dörner Katerina , Frank Matthias , Gelisio Luca , Jernigan Rebecca , Kirkwood Henry , Kloos Marco , Koliyadu Jayanath , Mariani Valerio , Miller Mitchell D. , Mills Grant , Nelson Garrett , Olmos Jose L. , Sadri Alireza , Sato Tokushi , Tolstikova Alexandra , Xu Weijun , Ourmazd Abbas , Spence John H. C. , Schwander Peter , Barty Anton , Chapman Henry N. , Fromme Petra , Mancuso Adrian P. , Phillips George N. , Bean Richard , Pollack Lois , Schmidt Marius
Published: November 2020

In this study, we follow the diffusion and buildup of occupancy of the substrate ceftriaxone inM. tuberculosisβ-lactamase BlaC microcrystals by structural analysis of the enzyme substrate complex at single millisecond time resolution. We also show the binding and the reaction of an inhibitor, sulbactam, on a slower millisecond time scale. We use the ‘mix-and-inject’ technique to initiate these reactions by diffusion, and determine the resulting structures by serial crystallography using ultrafast, intense X-ray pulses from the European XFEL (EuXFEL) arriving at MHz repetition rates. Here, we show how to use the EuXFEL pulse structure to dramatically increase the size of the data set and thereby the quality and time resolution of “molecular movies” which unravel ligand binding and enzymatically catalyzed reactions. This shows the great potential for the EuXFEL as a tool for biomedically relevant research, particularly, as shown here, for investigating bacterial antibiotic resistance.

One Sentence Summary

Direct observation of fast ligand binding in a biomedically relevant enzyme at near atomic resolution with MHz X-ray pulses at the European XFEL.
Learning epistatic polygenic phenotypes with Boolean interactions
Authors: Behr Merle , Kumbier Karl , Cordova-Palomera Aldo , Aguire Matthew , Ronen Omer , Ye Chengzhong , Ashley Euan , Butte Atul J. , Arnaout Rima , Brown Ben , Priest James , Yu Bin
Published: November 2020

Detecting epistatic drivers of human phenotypes is a considerable challenge. Traditional approaches use regression to sequentially test multiplicative interaction terms involving pairs of genetic variants. For higher-order interactions and genome-wide large-scale data, this strategy is computationally intractable. Moreover, multiplicative terms used in regression modeling may not capture the form of biological interactions. Building on the Predictability, Computability, Stability (PCS) framework, we introduce the epiTree pipeline to extract higher-order interactions from genomic data using tree-based models. The epiTree pipeline first selects a set of variants derived from tissue-specific estimates of gene expression. Next, it uses iterative random forests (iRF) to search training data for candidate Boolean interactions (pairwise and higher-order). We derive significance tests for interactions, based on a stabilized likelihood ratio test, by simulating Boolean tree-structured null (no epistasis) and alternative (epistasis) distributions on hold-out test data. Finally, our pipeline computes PCS epistasis p-values that probabilisticly quantify improvement in prediction accuracy via bootstrap sampling on the test set. We validate the epiTree pipeline in two case studies using data from the UK Biobank: predicting red hair and multiple sclerosis (MS). In the case of predicting red hair, epiTree recovers known epistatic interactions surroundingMC1Rand novel interactions, representing non-linearities not captured by logistic regression models. In the case of predicting MS, a more complex phenotype than red hair, epiTree rankings prioritize novel interactions surroundingHLA-DRB1, a variant previously associated with MS in several populations. Taken together, these results highlight the potential for epiTree rankings to help reduce the design space for follow up experiments.
Prophage elements function as reservoir for antibiotic resistance and virulence genes in nosocomial pathogens
Authors: Kondo Kohei , Kawano Mitsuoki , Sugai Motoyuki
Published: November 2020

Prophages are often involved in host survival strategies and contribute toward increasing the genetic diversity of the host genome. Prophages also drive horizontal propagation of various genes as vehicles. However, there are few retrospective studies contributing to the propagation of antimicrobial resistance (AMR) and virulence factor (VF) genes by prophage. In this study, we extracted complete genome sequences of seven pathogens, including ESKAPE bacteria andEscherichia colideposited in a public database, and examined the distribution of both AMR and VF genes in certain genomic regions of prophage, including prophage-like element. We found that the ratios of AMR and VF genes greatly varied among the seven species. More than 55% ofEnterobacter cloacaestrains had VF genes, but only 0.8% ofKlebsiella pneumoniaestrains had VF genes from prophages. The prophage types carrying AMR genes were detected in a broad range of hosts, whereas prophages containing VF genes were conserved in only one or two species, suggesting that distribution patterns of prophages were different between prophages encoding AMR or VF genes. We also found that the prophage containing class 1 integrase possessed a significantly higher number of AMR genes than prophages with no class 1 integrase. Moreover, AMR genes in the prophage were located near transposase and integrase. The results of this study reveal a comprehensive picture of AMR and VF genes present in prophage elements and provide new insights into the horizontal transfer of genes associated with antimicrobial resistance and pathogenicity.

Importance

Although we believe phages play an important role in horizontal gene transfer in exchanging genetic material, we do not know the distribution of the antimicrobial resistance and/or virulence genes in prophages. We collected different prophage elements from the complete genome sequence of seven species –Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, andEnterobacter cloacae, as well asEscherichia coli–, and characterized the distribution of antimicrobial resistance and virulence genes encoded in the prophage region. While virulence genes in prophage were found to be species-specific, antimicrobial resistance genes in prophages were highly conserved in various species. Integron structure was detected within prophage regions in almost all of the genera. Maximum of 11 antimicrobial resistance genes were found in a single prophage region, suggesting that prophages act as a reservoir for antimicrobial resistance genes. Our results highlight new insights on prophages as horizontal gene carriers.
HealthCall: Smartphone Enhancement of Brief Interventions to Improve Medication Adherence Among Patients in HIV care
Authors: Hasin Deborah , Aharonovich Efrat , Zingman Barry , Stohl Malka , Walsh Claire , Elliott Jennifer C. , Fink David , Knox Justin , Durant Sean , Menchaca Raquel , Sharma Anjali
Published: November 2020

Background

Heavy drinking among People Living With HIV (PLWH) reduces antiretroviral adherence and worsens health outcomes. Lengthy interventions to reduce drinking and improve adherence are not feasible in most HIV primary care settings, and patients seldom follow referrals to outside treatment. Utilizing visual and video features of smartphone technology, we developed and tested HealthCall as an electronic (smartphone) means of increasing patient involvement in brief intervention to reduce drinking and improve medication adherence without making unfeasible demands on providers.

Methods

Alcohol-dependent patients at a large urban HIV clinic were randomized to one of three groups: (1) Motivational Interviewing (MI) plus HealthCall (n=39), (2) NIAAA Clinician’s Guide (CG) plus HealthCall (n=38), or (3) CG-only (n=37). Baseline interventions targeting drinking reduction and medication adherence were ∼25 minutes, with brief (10-15 min) booster sessions at 30 and 60 days. HealthCall involved daily use of the smartphone for 3-5 min/day, covering drinking, medication adherence, and other aspects of the prior 24 hours. Our outcome, assessed at 30 and 60 days, and 3, 6 and 12 months, was ART adherence (using unannounced phone pill-count method; possible adherence scores: 0%-100%). Analysis: generalized linear mixed models with pre-planned contrasts.

Results

Study retention was excellent (85%-94% across timepoints) and unrelated to treatment arm or patient characteristics. ART adherence was generally high throughout follow-up, with some decline by 12 months. Although both CG+HealthCall and MI+HealthCall evidenced benefits early in follow-up, by 6 months, ART adherence was 11% better among patients in CG+HealthCall than in CG-only (p=0.03) and 9% better than among patients in MI+HealthCall (p=0.07). Efficacy differed slightly by gender (p=.09).

Conclusion

HealthCall paired with CG resulted in better ART adherence than CG alone. MI+HealthCall’s early benefits diminished over time. Given the importance of ART adherence and drinking reduction among PLWH, and the low costs and time required for HealthCall, pairing HealthCall with brief interventions within HIV clinics merits widespread consideration.
Chromosome structure due to phospho-mimetic H2A modulates DDR through increased chromatin mobility
Authors: Fernandez Fabiola Garcia , Lemos Brenda , Khalil Yasmine , Batrin Renaud , Haber James E. , Fabre Emmanuelle
Published: November 2020

In budding yeast and mammals, double strand breaks trigger global chromatin mobility together with the rapid phosphorylation of the histone H2A over an extensive region of the chromatin. To assess the role of H2A phosphorylation in this response to DNA damage, we have constructed strains where H2A has been mutated to the phospho-mimetic H2A-S129E. We show that H2A-S129E mutant increases global motion of chromosomes even in the absence of DNA damage. The intrinsic chromatin mobility of H2A-S129E is not due to checkpoint activation, histone degradation or kinetochore anchoring. Rather, the increased intra-chromosomal distances observed in H2A-S129E mutant are consistent with chromatin structural changes. In this context, the Rad953BP1-dependent-checkpoint becomes dispensable. The increase in chromatin dynamics is favorable to NHEJ of a single double-strand break but is accompanied by a sharp decrease in inter-chromosomal translocation rates. We propose that changes in chromosomal conformation due to H2A phosphorylation are sufficient to modulate the DDR and maintain genome integrity.
QSM Reconstruction Challenge 2.0: Design and Report of Results
Authors: Bilgic Berkin , Langkammer Christian , Marques José P. , Meineke Jakob , Milovic Carlos , Schweser Ferdinand
Published: November 2020

Purpose

The aim of the second quantitative susceptibility mapping (QSM) reconstruction challenge (Oct 2019, Seoul, Korea) was to test the accuracy of QSM dipole inversion algorithms in simulated brain data.

Methods

A two-stage design was chosen for this challenge. The participants were provided with datasets of multi-echo gradient echo images synthesized from two realisticin silicohead phantoms using an MR simulator. At the first stage, participants optimized QSM reconstructions without ground-truths available to mimic the clinical setting. At the second stage, ground-truths were provided for parameter optimization.Submissions were evaluated using eight numerical metrics and visual ratings.

Results

A total of 98 reconstructions were submitted for stage 1 and 47 submissions for stage 2. Iterative methods had the best quantitative metric scores, followed by deep-learning and direct inversion methods. Priors derived from magnitude data improved the metric scores. Algorithms based on iterative approaches and Total Variation (and its derivatives) produced the best overall results. The reported results and analysis pipelines have been made public to allow researchers to compare new methods to the current state of the art.

Conclusion

The synthetic data provides a consistent framework to test the accuracy and robustness of QSM algorithms in the presence of noise, calcifications and minor voxel dephasing effects. Total Variation-based algorithmsproduced the best results along all metrics. Future QSM challenges should asses if this good performance with synthetic datasets translates to more realistic scenarios, where background fields and dipole-incompatible phase contributions are included.