bluuebunny/crossref_metadata_2025 huggingface dataset:
T82. THE IMPACT OF SMOKING ON LIFE EXPECTANCY IN PSYCHOTIC DISORDERS, AN ELECTRONIC CASE REGISTER COHORT STUDY
Authors: Chesney Edward , Robson Deborah , Patel Rashmi , Shetty Hitesh , Richardson Sol , Chang Chin-Kuo , McGuire Philip , McNeill Ann
Published: May 2020

Background

Schizophrenia, schizoaffective disorder and bipolar affective disorder are associated with a life expectancy at birth that is 10–20 years shorter than in the general population. The prevalence of cigarette smoking in people with these disorders is very high, but the extent to which this accounts for differences in mortality is unclear. We addressed this issue by examining the effect of smoking on life expectancy and survival in a large electronic healthcare database of patients receiving secondary mental healthcare in South East London.

Methods

Data on all patients with a diagnosis of schizophrenia, schizoaffective disorder or bipolar affective disorder from 1st January 2007 to 31st December 2018 was obtained. Smoking status was determined using unstructured text data extracted from electronic health records. Chiang’s method of abridged life tables was used to calculate estimates of life expectancy at birth according to gender and most commonly recorded smoking status. Cox proportional hazards models were used to estimate mortality risk and adjusted for a broad range of demographic and clinical variables.

Results

21,588 patients were included in the study of which 20,155 (93.4%) were classified as either smokers (16,717 [77.4%]) or non-smokers (3,438 (15.9%]). 2,434 (11.3%) participants died by the end of the observation period. In female patients, life expectancy at birth was 67.6 years in current smokers (95% CI: 66.4 to 68.8) and 74.9 years in non-smokers (95% CI: 72.8 to 77.0). In male patients, life expectancy at birth was 63.5 years in current smokers (95% CI: 62.5 to 64.5) and 68.5 years in non-smokers (95% CI: 64.4 to 72.6). Adjusted survival models showed that current smoking was associated with an increased risk of death, in both females (aHR = 1.42; 95% CI: 1.21–1.66) and males (aHR = 1.49; 95% CI: 1.25–1.79).

Discussion

Smoking may account for a substantial proportion of the reduced life expectancy in patients with psychotic disorders. Interventions to reduce tobacco smoking in patients with psychosis may therefore improve life expectancy in this group.
M24. NETWORK STRUCTURE OF PSYCHOPATHOLOGY SYMPTOMS IN A COMMUNITY SAMPLE OF YOUTH
Authors: Wang Emily , Mary Xavier Rose
Published: May 2020

Background

The field of network psychometrics has developed into a promising alternative to the common cause theory and depicts mental health disorders as arising from the interactions between individual symptoms. Currently, major depressive disorder and post-traumatic stress disorder have been the two main disorders studied using network models. In this study, we aimed to examine the network structure of psychopathology symptoms in a community youth sample to detect the most influential symptoms. We also identify influential bridge symptoms which may lead to comorbidities.

Methods

The sample (n = 2875) was taken from the Philadelphia Neurodevelopmental Cohort and comprised of youth between the ages of 11–21. 112 variables corresponding to 17 psychopathology symptom groups were used to build the network model. We estimated the network structure using a mixed graphical model. Edges were estimated using a pairwise weighted adjacency matrix with EBIC regularization at a default gamma level of 0.25. The relative influence of each node was determined using predictability and centrality measurements including node strength, closeness, and betweenness. A network was similarly created to detect the most influential bridge symptoms using community clusters.

Results

The network generated from 17 psychopathology symptom domains (comprising ADD, agoraphobia, conduct disorder, depression, generalized anxiety disorder, mania, OCD, ODD, panic disorder, phobia, psychosis, PTSD, general probes, separation anxiety, psychosis prodromal symptoms, social anxiety and suicide) had several distinct cluster regions and two independent psychosis prodromal symptom nodes. No negative associations were observed in the network. The strongest edge regression coefficient (1.593) was detected between a general screening probe asking whether the subject had received previous treatment and a psychosis variable related to hallucination.

An OCD item eliciting subject’s fear over accidentally doing something bad had the greatest average centrality measurement (2.317) followed closely by a conduct disorder item eliciting if the subject had ever threatened someone (2.254). Two depression items - irritability (2.228) and depressive mood (1.825) had the largest average bridge centrality values.

History of inpatient treatment (0.997), fear of traveling in a car (0.989) and compulsive checking (0.989) had the largest predictability values, suggesting they could potentially be effective intervention targets.

Discussion

OCD and conduct disorder symptoms had the largest centrality values and are influential symptoms that could potentially be used to more effectively screen youth for mental health disorders. Depression symptoms had the largest bridge centrality values and should be targeted to prevent comorbidity of associated symptoms. Understanding psychopathology symptom networks could potentially lead to greater insights for prevention and individualizing treatments.
M36. VIRTUAL REALITY COGNITIVE BEHAVIORAL THERAPY FOR PARANOID DELUSIONS
Authors: Berkhof Maureen , van der Stouwe Elisabeth , Lestestuiver Bart , van ‘t Hag Erna , Maarten de Vos , Van der Gaag Mark , Veling Wim
Published: May 2020

Background

Seventy percent of patients with schizophrenia and other psychotic disorders has paranoid delusions. Paranoid delusions are associated with great distress, hospital admission and social isolation. Cognitive behavioral therapy (CBT) is the main psychological treatment, but the median effect size is only small to medium. Virtual reality (VR) has a great potential to improve psychological treatment of paranoid delusions. In a previous study, we found that VR based CBT (VRcbt) for paranoid delusions is effective compared to waiting list. As a next step, a direct comparison with standard CBT is needed. The aim of this project is to investigate if VRcbt is more (cost-)effective than standard CBT for treatment of paranoid delusions and improving daily life social functioning of patients with schizophrenia and related psychotic disorders. Three research questions will be addressed: 1. Does VRcbt lead to better clinical and social outcomes? 2. Are fewer treatment sessions needed to achieve meaningful clinical change? 3. Is VRcbt more cost-effective at 6 months follow-up?

Methods

A total of 106 patients with DSM-5 diagnosis of psychotic disorder and at least moderate level of paranoid ideations will be randomized to either VRcbt or standard CBT treatment for paranoid delusions. VRcbt consists of maximum 16 sessions in virtual social situations that trigger paranoid ideations and distress, delivered in an 8–12 week time frame. Standard CBT also consists of maximum 16 sessions, aiming at reappraisal of the meaning of paranoid beliefs to reduce distress and improve coping in daily life, including the use of exposure and behavioral experiments.

Participants will be interviewed and tested at baseline, post-treatment and at six months follow-up. Primary outcome is level of paranoid ideations in daily life social situations, measured with ecological momentary assessments (EMA) at semi-random moments ten times a day during seven days, before and after treatment. Every session, participants and therapists will rate level of paranoid ideation and global clinical impression.

Results

Seven mental health services throughout the Netherlands participate in this RCT. Up until now, fourteen psychologists have been trained in VRcbt and the first patients have been included in the trial.

Discussion

Comparison of VRcbt and cbt will provide information about the relative (cost-)effectiveness of VRcbt for this population. VRcbt may become the preferred psychological treatment for paranoid delusions and social anxiety in patients with psychotic disorder.
M73. DRIVING ABILITIES IN PATIENTS WITH SCHIZOPHRENIA
Authors: Pardeller Silvia , Biedermann Falko , Haibach Maria , Holzner Bernhard , Kemmler Georg , Kurzthaler Ilsemarie , Hofer Alex
Published: May 2020

Background

Driving ability is a relevant factor of individual autonomy for patients suffering from psychiatric diseases. The aim of this naturalistic study was to determine the driving ability of clinically stable outpatients with schizophrenia and to determine relevant parameters for possible deficits.

Methods

We included 50 outpatients with schizophrenia (ICD-10) between the ages of 18 and 65 who were on stable psychopharmacological treatment for at least three months. By means of the Wiener Testsystem (Schuhfried), reaction behaviour, the ability to observe and gain overview, reaction time, certainty in decision making as well as concentration and attention were tested. Symptomatology and extrapyramidal motor symptoms (EPS) were investigated by using the Positive and Negative Syndrome Scale (PANSS) and the Modified Simpson Angus Scale (MSAS), respectively.

Results

The mean PANSS score of 55.3 ± 16.2 indicated that patients were merely mildly ill at the time of study inclusion. 48% had a MSAS score ≥3. 44% had adequate driving-specific abilities. 20% showed slight psychomotor impairments, and 36 % were considered as unfit to drive. 41.1% of the patients with a valid driver’s license were not able to drive. There was a strong correlation between EPS and driving ability, while residual symptomatology was not relevant in this context.

Discussion

Personal mobility is an important aspect of quality of life in people with schizophrenia. Possible danger for the general public may be conflicting with this point of view. Our investigation suggests that EPS have a major influence on the ability to drive. The missing correlation between residual symptomatology and driving abilities, on the other hand, may be explained by low mean PANSS scores. Further studies with larger sample sizes are urgently needed to address this issue.
M89. PHARMACOLOGICAL INTERVENTIONS FOR SMOKING CESSATION AMONG PEOPLE WITH SCHIZOPHRENIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Siskind Dan , Wu Brian , Wong Tommy , Kisely Steve
Published: May 2020

Background

People living with schizophrenia are 3 times more likely to smoke than the general population, and have fewer and less successful quitting attempts. In concert with psychosocial quit interventions, there is a need for evidence based pharmacological interventions to assist people living with schizophrenia achieve smoking abstinence.

Methods

We systematically searched PubMed, PsycInfo, EMBASE and Cochrane for randomised controlled trials of pharmacological interventions for reducing smoking among people living with schizophrenia. We conducted pairwise and network meta-analyses of effectiveness of interventions for achieving abstinence and reduction in smoking. We also examined psychiatric and physical adverse events of interventions.

Results

Nineteen studies were included in the systematic review. Data was available for buproprion, varenicline and nicotine replacement therapy (NRT). Buproprion (RR 3.4, 95%CI 1.6–7.3, p=0.002), varenicline (RR 3.8, 95%CI 2.0–7.2, p<0.001) and NRT (RR 4.3, 95%CI 1.7–10.7, p=0.002) were all associated with increased rates of abstinence in pairwise meta-analyses. In a network meta-analysis varenicline was superior to buproprion (RR 2.0, 95%CI 1.0–3.9), however there was no statistically significant difference between varenicline and NRT or buproprion and NRT. Varenicline was associated with higher rates of nausea than placebo.

Discussion

Buproprion, varenicline and NRT were all superior to placebo for achieving abstinence. Varenicline appears to be superior to buproprion for achieving abstinence, however varenicline is associated with higher rates of nausea.
M218. RELATIONSHIP BETWEEN JUMPING TO CONCLUSIONS AND OTHER COGNITIVE BIASES AND SOCIAL COGNITION IN PEOPLE WITH SCHIZOPHRENIA
Authors: Garcia-Franco Mar , Vilamala-Anton Sonia , Prat Gemma , Jose EScandell Maria , Martínez Jose Ramón , Cano Ivan , Muñoz Ana , Torras Romina , Calderón Maria , Verdaguer Marina , Call Maria , Ochoa Susana
Published: May 2020

Background

Deficits in jumping to conclusions and social cognition have been described in people with schizophrenia. The aims of the study are to relate jumping to conclusions with social cognition and other cognitive biases in people with schizophrenia attended in rehabilitation services.

Methods

A descriptive study was performed. The subjects of our study were persons from 18 to 65 years old, attended in rehabilitation services, with schizophrenia diagnoses and other diagnoses with presence of psychotic symptoms (depression, bipolar disorder, borderline disorder, delusional disease, schizoaffective, and schizotypal personality).

The variables included were JTC considered three beads tasks with different proportions: 85:15%, 60:40% and 60:40% salient task. Moreover, cognitive insight (BCIS), attributional style (IPSAQ), and Hinting Task -Theory of Mind (ToM) were assessed.

A T student analysis was done in order to compare JTC with the rest of the quantitative variables.

Results

People who jump to conclusions in the salient task scored higher in self-certainty BCIS (p=0.028), in self attribution for negative events (p=0.036) and lower in attribution to other people of negative events (p=0.028). A tendency was found between the presence of JTC and ToM (p=0.051). In the task of 85-15 only a tendency was found between presence of JTC and higher scores in the personalizing bias (p=0.079). Moreover, in the task of 60:40 a tendency was found between presence of JTC and worse performance in the ToM test (p=0.051).

Discussion

We found a relationship between jumping to conclusions and self-certainty and self-attributions for negative events; as well as, it is a tendency that higher jumping to conclusions is related with worst ToM. There are important clinic implications of this, because we know that jumping to conclusions and theory of mind is related with the formation and maintenance of delusions.
S77. ROLE OF DOPAMINE AND GLUTAMATE TRANSPORTERS IN GENERATION OF ANTIPSYCHOTIC EFFICACY
Authors: Kruyer Anna , Parrilla Carrero Jeffrey , Amato Davide
Published: May 2020

Background

Antipsychotic drugs are the first line intervention to treat psychosis in schizophrenia and D2 receptor blockade is thought to be their primary mechanism of action. However, multiple lines of evidence from human and animal studies show that D2 receptor blockade is not always correlated with markers of antipsychotic efficacy. We previously demonstrated that reduced antipsychotic efficacy occurs after chronic antipsychotic administration in rodents despite stable D2 blockade, examined using PET imaging. Instead, we found that changes in expression of the dopamine transporter (DAT) were associated with decreases in endogenous dopamine and dopamine-mediated autoinhibition. These studies have led us to examine the DAT as a critical player in generation of an antipsychotic response.

Methods

Using antisense morpholino oligonucleotides, administered for 3 consecutive days using Long Evans rats, we selectively blocked translation of DAT or GLT-1 mRNA in the core of the nucleus accumbens, a brain region critical for motor outputs in response to salient stimuli. Baseline locomotion was monitored prior to and after an acute i.p. injection of haloperidol. Next, locomotion was monitored in response to a tail pinch or acute i.p. administration of cocaine. Transporter expression was quantified during acute or chronic haloperidol treatment using confocal microscopy.

Results

We found that DAT knockdown enhanced tail pinch-induced locomotion after acute haloperidol administration. Additionally, knockdown of the glutamate transporter GLT-1 strongly enhanced locomotion induced by tail pinch or cocaine injection after antipsychotic treatment. Confocal analysis of GLT-1 expression after acute or chronic haloperidol revealed significant GLT-1 up-regulation during a time period associated with antipsychotic efficacy.

Discussion

Our findings demonstrate a cause/effect relationship between reduced DAT and the behavioral response to an acute injection of antipsychotics in rodents. In all, our data point to the importance of both dopamine and glutamate uptake in the efficacy of antipsychotic drugs and argue against a D2-centric hypothesis of antipsychotic action.
S226. DEVELOPMENT OF EARLY DETECTION AND EARLY INTERVENTION SERVICES WITHIN PSYCHIATRIC CARE IN THE CZECH REPUBLIC
Authors: Dvorakova Monika , Kondratova Lucie
Published: May 2020

Background

Early Detection (ED) and Early Intervention (EI) are specialized services aiming at early diagnosis and early treatment of psychosis. There are evidence-based effects of ED and EI services that cannot be overlooked, such as early recognition of prodromal symptoms, preventing the adverse effects of untreated psychosis, lowering the risk of hospitalization, and therefore it has become part of the ongoing mental health care reform in the Czech Republic.

Methods

A total of 12 mental health professionals were trained in order to provide specialised ED and EI services within three regions in the Czech Republic – Prague 8, Pilsen and Blansko. All people aged 16 to 60 years who live in a predefined catchment area and are (a) at risk of developing psychosis, (b) in the first episode of psychosis or (c) are treated with psychosis for less than 3 years, are eligible for the service. Standardised assessment tools are being used for clients’ assessment (GAF, HoNOS, PANSS and CAARMS).

Results

Three multidisciplinary ED and EI teams were established in 2019 in the Czech Republic. Psychiatrist, psychologist, nurse and social worker are involved in each team. Presented data will describe psychosocial interventions and detection activities from 1/4/2019 to 1/4/2020.

Discussion

The psychiatric care system in the Czech Republic is predominantly built on large psychiatric institutions and there is a lack of community mental health services. Since the hospitalization is usually the first contact with mental health care services, there is a high potential of ED and EI services to prevent admission and readmission to the psychiatric hospital through early recognition of prodromal symptoms and reduction of the duration of untreated psychosis.
S239. EVALUATION OF A POINT OF CARE DEVICE IN IMPROVING PHYSICAL HEALTH CHECK UPTAKE IN TWO COMMUNITY MENTAL HEALTH TEAMS
Authors: Butler Joseph , de Cassan Simone , Lennox Belinda , Turner Phillip , Glogowska Margaret , Fanshawe Tom , Hayward Gail
Published: May 2020

Background

Patients with Severe Mental Illness (SMI) have a life expectancy 15–20 years below that of the general population, mediated predominantly by the complications of poor cardiovascular health. Physical healthcare for this population is shared between General Practice (GP) and Community Mental Health Teams (CMHTs) and encompasses a NICE-recommended annual physical health check, to screen for cardiovascular complications. Audit findings in 2017 across the South of England show poor physical health check completion (38%), typically because HbA1c and Lipid Panel blood tests were omitted. Traditionally, patients are advised to attend their GP surgery for these tests, which can be a challenge for patients with SMI.

There is a growing market of POC devices able to calculate an HbA1c or Lipid Panel in rapidly from ‘fingerprick’ samples of blood at, or near the site of the patient. The Cardiovascular Monitoring in Mental Health (CARMEN) project hypothesised that test uptake would be improved by implementation of a ‘Point of Care’ (POC) blood testing device in two CMHTs.

Methods

We embedded the ‘Afinion’ device into an Early Intervention Team and an Adult Mental Health Team in Oxfordshire for six months. Training was provided to care coordinators with ongoing support to facilitate engagement with the device. We compared rates of blood test and full physical health check completion in the intervention teams to a matched early intervention team and adult mental health term in Buckinghamshire. We performed semi-structured interviews with patients receiving POC-augmented care and clinicians from the intervention teams.

Results

Data showed that whilst the Adult Mental Health team did not engage with the device and saw no change in outcomes, the Early Intervention Team did engage and increased rates of physical health check completion from 22.6% to 40.3% of their caseload per 6 months. Completion in the control CMHT was 7.8%. Similar trends were seen in rates of HbA1c and Lipid Panel completion. Qualitative interviews revealed universal patient support for POC and diverse attitudes to the role of the mental health teams in providing physical healthcare. We explored how clinicians engaged and why they didn’t engage with the device, and how access to POC modulated the therapeutic relationship.

Discussion

Our findings show that using POC for Physical Health Checks is acceptable to patients with SMI and mental health care clinicians, many of whom are from a non-clinical background. In teams where it is well adopted, POC testing can improve physical health check completion in the SMI population, although our qualitative findings highlight important considerations for maximising clinician engagement.
Effects of timing and size of meals prior to farrowing on sow and litter performance
Authors: Gourley Kiah M , Swanson Analicia J , Royall Rafe Q , DeRouchey Joel M , Tokach Mike D , Dritz Steve S , Goodband Robert D , Hastad Chad W , Woodworth Jason C
Published: May 2020

A total of 727 mixed parity (µ = 3.8) sows were used to evaluate the effects of timing and size of meals before farrowing on sow and litter performance. Upon entry to the farrowing house (day 113), sows were blocked by weight within parity and allotted to one of three three feeding management strategies until farrowing: (1) 2.7 kg lactation diet (1.15% standardized ileal digestible lysine and 2,153 kcal/kg net energy) once daily at 0700 hours; (2) four daily meals of 0.67 kg (0100, 0700, 1300, and 1900 hours); (3) ad libitum lactation diet and encouraged to consume feed at 0100, 0700, 1300, and 1900 hours. After farrowing, all sows were provided lactation diets fed on an ad libitum basis until weaning. Data were analyzed for treatment effects within parity category in a mixed model with block as a random effect. Feeding sows ad libitum before farrowing tended to reduce sow body weight (BW) loss (P = 0.077) and reduce backfat (BF) loss (P = 0.003) from entry into the farrowing house until weaning compared with sows fed four daily meals, with sows fed once daily intermediate. Litter gain from 24 h to weaning tended to be greater (P = 0.073) in sows fed on an ad libitum basis or four times daily prior to farrowing compared with sows fed one meal. Piglet weaning weight increased (P = 0.050) in sows fed on an ad libitum basis before farrowing, compared with those fed one meal, with those fed four times daily intermediate. There was no evidence for difference in farrowing duration, stillborn rate, colostrum yield, or 24 h piglet survival regardless of treatment. However, from 24 h after farrowing to weaning, sows fed one daily meal prior to farrowing had an increased (P = 0.012) percentage of fall-behind pigs compared with sows fed on an ad libitum basis, and increased (P = 0.027) preweaning mortality compared with sows fed four daily meals, resulting in reduced (P = 0.006) weaned percentage compared with sows fed four daily meals. There was no evidence for difference (P > 0.10) in subsequent reproductive performance regardless of treatment. In conclusion, when sows were fed on an ad libitum basis from 2 to 3 d, before farrowing there was an observed improvement in sow BW and BF maintenance during lactation, and piglet weaning weight during lactation. Increased frequency of meals prior to farrowing improved the survival of pigs to weaning compared with sows fed a single meal prior to farrowing.
Bilateral tuberculous psoas abscess
Authors: Miloudi Mouhcine , Arsalane Lamiae , Kharrab Anas , El Kamouni Youssef , Zouhair Said
Published: May 2020

The unilateral psoas abscess is a rare disease that is often caused by common germs, including

Staphylococcus aureus

. Tuberculous origin and bilateral involvement are even rarer, especially in developed countries. It may be primary or secondary to a neighbourhood focus. We report a case of bilateral tuberculous abscess of psoas in an immunocompetent patient secondary to spondylodiscitis.
A stochastic, individual-based model for the evaluation of the impact of non-pharmacological interventions on COVID-19 transmission in Slovakia
Authors: Gasparek Miroslav , Racko Michal , Dubovsky Michal
Published: May 2020

The COVID-19 pandemic represents one of the most significant healthcare challenges that humanity faces. We developed a stochastic, individual-based model of transmission of COVID-19 in Slovakia. The proposed model is based on current clinical knowledge of the disease and takes into account the age structure of the population, distribution of the population into the households, interactions within the municipalities, and interaction among the individuals travelling between municipalities. Furthermore, the model incorporates the effect of age-dependent severity of COVID-19 and realistic trajectories of patients through the healthcare system. We assess the impact of the governmental non-pharmacological interventions, such as population-wide social distancing, social distancing within specific subsets of population, reduction of travel between the municipalities, and self-quarantining of the infected individuals. We also evaluate the impact of relaxing of strict restrictions, efficacy of the simple state feedback-based restrictions in controlling the outbreak, and the effect of superspreaders on the disease dynamics. Our simulations show that non-pharmacological interventions reduce the number of infected individuals and the number of fatalities, especially when the social distancing of particularly susceptible subgroups of the population is employed along with case isolation.
Mixed Chinese herbs and Western medicine for novel coronavirus disease 2019 (COVID-19): a mixed method review
Authors: Tai Zhang Yong , Tay Louisa , Goh Robby Miguel , Zhou Rui Shu , Wong Lin Ho , Wong Pang Ong
Published: May 2020

Background: Coronavirus disease 2019 (COVID-19) is a pandemic affecting millions around
the world. There is no existing pharmaceutical treatment that is known to be effective.
Preliminary data shows that San Yao San Fang (SYSF) has clinical benefits in patients with
COVID-19. The aim of this paper is to review existing data regarding the use of formulas
within San Yao San Fang in the treatment of COVID-19
Search Strategy: We searched through 5 databases for studies on SYSF and patients with
COVID-19 through April 2020.
Eligibility Criteria: We included studies that included formulas within San Yao San Fang
with or without Western interventions against Western interventions.
Main results: We included 7 studies involving 532 patients.
SYSF combined with Western interventions improved the recovery rate of symptoms such as
fever (Risk Ratio (RR) 0.40 (95% CI 0.24 to 0.66, P < 0.01)), cough (RR 0.56 (95% CI 0.38
to 0.82, P < 0.01)) and fatigue (RR 0.61 (95% CI 0.47 to 0.78, P < 0.01)) and other symptoms
such as headache, gastrointestinal symptoms, myalgia, dyspnoea and chest tightness (RR 0.63
(95% CI 0.47 to 0.83, P < 0.01)) as compared to the control group.
SYSF combined with Western interventions reduced the duration of fever as compared to the
control group. (Mean difference (MD) -1.18 (95% CI -1.45 to -0.91, P < 0.01))
In regards to adverse events, there is no statistical difference between the treatment group and
the control group. (RR 1.62 (95% CI 0.83 to 3.17, P = 0.16)).
SYSF combined with Western interventions did not show to significantly reduce duration of
hospitalisation as compared to the control group. (MD -0.73 (95% CI -5.19 to 3.73, P = 0.75))
Conclusion: SYSF appears to be clinically effective and safe. Further research is required to
ensure the efficacy of SYSF.
An SEIARD epidemic model for COVID-19 in Mexico: mathematical analysis and state-level forecast
Authors: Avila-Ponce de León Ugo , Pérez Ángel G. C. , Avila-Vales Eric
Published: May 2020

We propose an SEIARD mathematical model to investigate the current outbreak of coronavirus disease (COVID-19) in Mexico. Our model incorporates the asymptomatic infected individuals, who represent the majority of the infected population (with symptoms or not) and could play an important role in spreading the virus without any knowledge. We calculate the basic reproduction number (R0) via the next-generation matrix method and estimate the per day infection, death and recovery rates. The local stability of the disease free equilibrium is established in terms of R0. A sensibility analysis is performed to determine the relative importance of the model parameters to the disease transmission. We calibrate the parameters of the SEIARD model to the reported number of infected cases and fatalities for several states in Mexico by minimizing the sum of squared errors and attempt to forecast the evolution of the outbreak until August 2020.
Estimating the true (population) infection rate for COVID-19: A Backcasting Approach with Monte Carlo Methods
Authors: Phipps Steven J. , Grafton R. Quentin , Kompas Tom
Published: May 2020

Differences in COVID-19 testing and tracing across countries, as well as changes in testing within each country overtime, make it difficult to estimate the true (population) infection rate based on the confirmed number of cases obtained through RNA viral testing. We applied a backcasting approach, coupled with Monte Carlo methods, to estimate a distribution for the true (population) cumulative number of infections (infected and recovered) for 15 countries where reliable data are available. We find a positive relationship between the testing rate per 1,000 people and the implied true detection rate of COVID-19, and a negative relationship between the proportion who test positive and the implied true detection rate. Our estimates suggest that the true number of people infected across our sample of 15 developed countries is 18.2 (5-95% CI: 11.9-39.0) times greater than the reported number of cases. In individual countries, the true number of cases exceeds the reported figure by factors that range from 1.7 (5-95% CI: 1.1-3.6) for Australia to 35.6 (5-95% CI: 23.2-76.3) for Belgium.
Extra base hits: widespread empirical support for instantaneous multiple-nucleotide changes
Authors: Lucaci Alexander G , Wisotsky Sadie R , Shank Stephen D. , Weaver Steven , Kosakovsky Pond Sergei L.
Published: May 2020

Despite many attempts to introduce evolutionary models that permit substitutions that instantly alter more than one nucleotide in a codon, the prevailing wisdom remains that such changes are rare and generally negligible (or are reflective of non-biological artifacts, such as alignment errors), and codon models continue to posit that only single nucleotide change have non-zero rates. We develop and test a simple hierarchy of codon-substitution models with non-zero evolutionary rates for only one-nucleotide (1H), one- and two-nucleotide (2H), or any (3H) codon substitutions. Using 35,000 empirical alignments, we find widespread statistical support for multiple hits: 58% of alignments prefer models with 2H allowed, and 22% – with 3H allowed. Analyses of simulated data suggest that these results are not likely to be due to simple artifacts such as model misclassification or alignment errors. Further modeling revealed that synonymous codon island jumping among codons encoding serine, especially along short branches, contributes significantly to this 3H signal. While serine codons were prominently involved in multiple-hit substitutions, there were other common exchanges contributing to better model fit. It appears that a small subset of sites in most alignments have unusual evolutionary dynamics not well explained by existing model formalisms, and that commonly estimated quantities, such as dN/dS ratios may be biased by model misspecification. Our findings highlight the need for continued evaluation of assumptions underlying workhorse evolutionary models and subsequent evolutionary inference techniques. We provide a software implementation for evolutionary biologists to assess the potential impact of extra base hits in their data in the HyPhy package.
Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals
Authors: Robbiani Davide F. , Gaebler Christian , Muecksch Frauke , Lorenzi Julio C. C. , Wang Zijun , Cho Alice , Agudelo Marianna , Barnes Christopher O. , Gazumyan Anna , Finkin Shlomo , Hagglof Thomas , Oliveira Thiago Y. , Viant Charlotte , Hurley Arlene , Hoffmann Hans-Heinrich , Millard Katrina G. , Kost Rhonda G. , Cipolla Melissa , Gordon Kristie , Bianchini Filippo , Chen Spencer T. , Ramos Victor , Patel Roshni , Dizon Juan , Shimeliovich Irina , Mendoza Pilar , Hartweger Harald , Nogueira Lilian , Pack Maggi , Horowitz Jill , Schmidt Fabian , Weisblum Yiska , Michailidis Eleftherios , Ashbrook Alison W. , Waltari Eric , Pak John E. , Huey-Tubman Kathryn E. , Koranda Nicholas , Hoffman Pauline R. , West Anthony P. , Rice Charles M. , Hatziioannou Theodora , Bjorkman Pamela J. , Bieniasz Paul D. , Caskey Marina , Nussenzweig Michel C.
Published: May 2020

During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21–5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
From cartoons to quantitative models in Golgi transport
Authors: Quiros D. Nicolas , Mayorga Luis S.
Published: May 2020

Cell biology is evolving to become a more formal and quantitative science. In particular, several mathematical models have been proposed to address Golgi self-organization and protein and lipid transport. However, most scientific articles about the Golgi apparatus are still using static cartoons to represent their findings that miss the dynamism of this organelle. In this report, we show that schematic drawings of Golgi trafficking can be easily translated into an Agent-Based Model (ABM) using the Repast platform. The simulations generate an active interplay among cisternae and vesicles rendering quantitative predictions about Golgi stability and transport of soluble and membrane-associated cargoes. The models can incorporate complex networks of molecular interactions and chemical reactions by association with COPASI, a software that handles Ordinary Differential Equations. The strategy described provides a simple, flexible, and multiscale support to analyze Golgi transport. The simulations can be used to address issues directly linked to the mechanism of transport or as a way to incorporate the complexity of trafficking to other cellular processes that occur in dynamic organelles.
PhylSim: A New Phylogenetic Tool for Modeling Trait Evolution and Speciation
Authors: Spivakovsky P. , Lio P. , Clark M. S.
Published: May 2020

We present a new software tool in R, the PhylSim package, which allows the user to simulate trait evolution on a phylogeny, while varying the speciation rate and evolutionary model over the course of the simulation. In particular, the user can specify any number of regimes, with a different speciation rate for each regime, or set the speciation rate to vary when the value of a trait exceeds a certain threshold. The evolutionary model can also be varied as many times as necessary over the course of the simulation, to account for traits tending toward different optima at different periods in evolutionary history. We illustrate the use of the package with an example, a simulation of the adaptive radiation of Antarctic notothenioids in the Southern Ocean.
Disease responses of hexaploid spring wheat (Triticum aestivum) culms exhibiting premature senescence (dead heads) associated withFusarium pseudograminearumcrown rot
Authors: Knight N. L. , Macdonald B. , Percy C. , Sutherland M. W.
Published: May 2020

Hexaploid spring wheat (Triticum aestivum) may exhibit significant crown rot disease responses to infection byFusarium pseudograminearum, with a range of susceptibility levels available in commercial cultivars. Dry conditions during grain-fill may lead to the expression of prematurely senescing culms, which typically fail to set grain. Assessment of hexaploid spring wheat plants exhibiting both non-senescent and prematurely senescent culms was performed using visual discolouration,Fusarium pseudograminearumbiomass, vascular colonisation and quantification of wheat DNA in culm sections sampled at three different heights above the crown and at the peduncle. A comparison of these parameters at four time points from milk development, when senescent culms are first observed, to maturity was conducted. Samples from six commercial cultivars were collected in 2014 from Narrabri and Tamworth, New South Wales and Wellcamp, Queensland. Prematurely senescent culms exhibited greater visual discolouration,Fusarium pseudograminearumbiomass and vascular colonisation than non-senescent culms in each cultivar. Colonisation of xylem and phloem tissue was extensive in the basal portions of prematurely senescent culms (36 to 99%), and suggests significant impacts on water and nutrient movement during crown rot disease. Maturation coincided with significant changes inFusarium pseudograminearumbiomass and vascular colonisation. Wheat DNA content varied among cultivars, culm conditions, culm sections and sampling times. The variation in the severity of disease states between culms of the same plant suggests that the timing of initiation of infection in individual culms may vary.
Phylogenetic origin and sequence features of MreB from the wall-less swimming bacteria Spiroplasma
Authors: Takahashi Daichi , Fujiwara Ikuko , Miyata Makoto
Published: May 2020

Spiroplasma are wall-less bacteria which belong to the phylum Tenericutes that evolved from Firmicutes including Bacillus subtilis. Spiroplasma swim by a mechanism unrelated to widespread bacterial motilities, such as flagellar motility, and caused by helicity switching with kinks traveling along the helical cell body. The swimming force is likely generated by five classes of bacterial actin homolog MreBs (SMreBs 1-5) involved in the helical bone structure. We analyzed sequences of SMreBs to clarify their phylogeny and sequence features. The maximum likelihood method based on around 5,000 MreB sequences showed that the phylogenetic tree was divided into several radiations. SMreBs formed a clade adjacent to the radiation of MreBH, an MreB isoform of Firmicutes. Sequence comparisons of SMreBs and Bacillus MreBs were also performed to clarify the features of SMreB. Catalytic glutamic acid and threonine were substituted to aspartic acid and lysine, respectively, in SMreB3. In SMreBs 2 and 4, amino acids involved in inter- and intra-protofilament interactions were significantly different from those in Bacillus MreBs. A membrane-binding region was not identified in most SMreBs 1 and 4 unlike many walled-bacterial MreBs. SMreB5 had a significantly longer C-terminal region than the other MreBs, which possibly forms a protein-protein interaction. These features may support the functions responsible for the unique mechanism of Spiroplasma swimming.
Loss of the conserved Alveolate kinase MAPK2 decouplesToxoplasmacell growth from the cell cycle
Authors: Hu Xiaoyu , O’Shaughnessy William J. , Beraki Tsebaot G. , Reese Michael L.
Published: May 2020

Mitogen-activated protein kinases (MAPKs) are a conserved family of protein kinases that regulate signal transduction, proliferation, and development throughout eukaryotes. The Apicomplexan parasiteToxoplasma gondiiexpresses three MAPKs. Two of these, ERK7 and MAPKL1, have been respectively implicated in the regulation of conoid biogenesis and centrosome duplication. The third kinase, MAPK2, is specific to and conserved throughout Alveolata, though its function is unknown. We used the auxin-inducible degron system to determine phenotypes associated with MAPK2 loss-of-function inToxoplasma. We observed that parasites lacking MAPK2 failed to duplicate their centrosomes and therefore did not initiate daughter-cell budding, which ultimately led to parasite death. MAPKL2-deficient parasites initiated, but did not complete DNA replication, and arrested prior to mitosis. Surprisingly, the parasites continued to grow in size and to replicate their Golgi, mitochondria, and apicoplasts. We found that the failure in centrosome duplication is distinct from the phenotype caused by depletion of MAPKL1. As we did not observe MAPK2 localization at the centrosome at any point in the cell cycle, our data suggest MAPK2 regulates a process at a distal site that is required for completion of centrosome duplication and initiation of parasite mitosis.

Importance

Toxoplasma gondiiis a ubiquitous intracellular protozoan parasite that can cause severe and fatal disease in immunocompromised patients and the developing fetus. Rapid parasite replication is critical for establishing a productive infection. Here, we demonstrate that aToxoplasmaprotein kinase called MAPK2 is conserved throughout Alveolata and essential for parasite replication. We found that parasites lacking MAPK2 protein were defective in the initiation of daughter cell budding and were rendered inviable. Specifically, TgMAPK2 appears to be required for centrosome replication at the basal end of the nucleus, and its loss causes arrest early in parasite division. MAPK2 is unique to Alveolata and not found in metazoa, and likely is a critical component of an essential parasite-specific signaling network.
Functional Connectivity of the Precuneus Reflects Effectiveness of Visual Restitution Training in Chronic Hemianopia
Authors: Halbertsma Hinke N. , Elshout Joris A. , Bergsma Douwe P. , Norris David G. , Cornelissen Frans W. , van den Berg Albert V. , Haak Koen V.
Published: May 2020

Visual field defects in chronic hemianopia can improve through visual restitution training, yet not all patients benefit equally from this long and exhaustive process. Here, we asked if resting-state functional connectivity prior to visual restitution could predict training success. In two training sessions of eight weeks each, 20 patients with chronic hemianopia performed a visual discrimination task by directing spatial attention towards stimuli presented in either hemifield, while suppressing eye movements. We examined two effects: a sensitivity change in the attended (trained) minus the unattended (control) hemifield (i.e., a training-specific improvement), and an overall improvement (i.e., a total change in sensitivity after both sessions). We then identified five visual resting-state networks and evaluated their functional connectivity in relation to both training effects. We found that the functional connectivity strength between the anterior Precuneus and the Occipital Pole Network was positively related to the attention modulated (i.e., training-specific) improvement. No such relationship was found for the overall improvement or for the other visual networks of interest. Our finding suggests that the anterior Precuneus plays a role in training-induced visual field improvements. The resting-state functional connectivity between the anterior Precuneus and the Occipital Pole Network may thus serve as an imaging-based biomarker that quantifies a patient’s potential capacity to direct spatial attention. This may help to identify hemianopia patients that are most likely to benefit from visual restitution training.
The plate-to-rod transition in trabecular bone loss is elusive
Authors: Felder A. A. , Monzem S. , De Souza R. , Javaheri B. , Mills D. , Boyde A. , Doube M.
Published: May 2020

Changes in trabecular micro-architecture are key to our understanding of osteoporosis. Previous work focusing on structure model index (SMI) measurements have concluded that disease progression entails a shift from plates to rods in trabecular bone, but SMI is heavily biased by bone volume fraction. As an alternative to SMI, we proposed the Ellipsoid Factor (EF) as a continuous measure of local trabecular shape between plate-like and rod-like extremes. We investigated the relationship between EF distributions, SMI and bone volume fraction of the trabecular geometry in a murine model of disuse osteoporosis as well as from human vertebrae of differing bone volume fraction. We observed a moderate shift in EF median (at later disease stages in mouse tibia) and EF mode (in the vertebral samples with low bone volume fraction) towards a more rod-like geometry, but not in EF maximum and minimum. These results support the notion that the plate to rod transition does not coincide with the onset of bone loss and is considerably more moderate, when it does occur, than SMI suggests. A variety of local shapes not straightforward to categorise as rod or plate exist in all our trabecular bone samples.
NanoCLUST: a species-level analysis of 16S rRNA nanopore sequencing data
Authors: Rodríguez-Pérez Héctor , Ciuffreda Laura , Flores Carlos
Published: May 2020

NanoCLUST is an analysis pipeline for classification of amplicon-based full-length 16S rRNA nanopore reads. It is characterized by an unsupervised read clustering step, based on Uniform Manifold Approximation and Projection (UMAP), followed by the construction of a polished read and subsequent Blast classification. Here we demonstrate that NanoCLUST performs better than other state-of-the-art software in the characterization of two commercial mock communities, enabling accurate bacterial identification and abundance profile estimation at species level resolution.

Availability and implementation

Source code, test data and documentation of NanoCLUST is freely available athttps://github.com/genomicsITER/NanoCLUSTunder MIT License.

Contact

cflores@ull.edu.es