bluuebunny/crossref_metadata_2025 huggingface dataset:
What is curbside consultation for the nurse practitioner?
Authors: Papermaster Amy , Champion Jane Dimmitt
Published: November 2019

Background:

Curbside or informal consultations between clinicians regarding patient care occur frequently in clinical practice. Evaluation of curbside consultation (CC) among nurse practitioners (NPs) is limited.

Purpose:

To develop an understanding of NP perceptions of the CC process.

Methodological orientation:

A qualitative descriptive design was used to assess the context of CCs among NPs. Inductive content analysis was conducted, and Atlas.ti was used to organize the data.

Sample:

Purposive sampling was used to recruit 20 NPs within primary care and specialty settings.

Conclusions:

Themes describing CC included the description of the CC process, advantages and disadvantages, documentation, legal liability, unspoken rules, and patient-centered engagement. There was a lack of consensus on the boundaries of the CC definition including difficulty in distinguishing a CC from a formal consultation. Generally, the NP acknowledges limitations and views the CC favorably as a helpful tool for receiving practical feedback and expanding learning, collegiality, and collaboration.

Implications for practice:

Findings provide insight regarding the common practice of CC in management of patients at the point of care, what it means to the NP, and a description of the breadth of the CC use. Given its potentially substantial impact on patient care, further assessment of the context of CC among NPs is obligatory.
Diaphragm protection: what should we target?
Authors: Schepens Tom , Dianti Jose
Published: November 2019

Purpose of review

Diaphragm weakness can impact survival and increases comorbidities in ventilated patients. Mechanical ventilation is linked to diaphragm dysfunction through several mechanisms of injury, referred to as myotrauma. By monitoring diaphragm activity and titrating ventilator settings, the critical care clinician can have a direct impact on diaphragm injury.

Recent findings

Both the absence of diaphragm activity and excessive inspiratory effort can result in diaphragm muscle weakness, and recent evidence demonstrates that a moderate level of diaphragm activity during mechanical ventilation improves ICU outcome. This supports the hypothesis that by avoiding ventilator overassistance and underassistance, the clinician can implement a diaphragm-protective ventilation strategy. Furthermore, eccentric diaphragm contractions and end-expiratory shortening could impact diaphragm strength as well. This review describes these potential targets for diaphragm protective ventilation.

A ventilator strategy that results in appropriate levels of diaphragm activity has the potential to be diaphragm-protective and improve clinical outcome. Monitoring respiratory effort during mechanical ventilation is becoming increasingly important.
Anti‐tumor Necrosis Factor‐alpha Exposure Impacts Vedolizumab Mucosal Healing Rates in Pediatric Inflammatory Bowel Disease
Authors: Jossen Jacqueline , Kiernan Bridget D. , Pittman Nanci , Dubinsky Marla C.
Published: November 2019

Background:

Vedolizumab (VDZ) is effective for treating both adult and pediatric onset inflammatory bowel disease (IBD). Clinical outcomes, however, have been reported to be superior in patients naïve to anti‐tumor necrosis factor (TNF). With the growing interest in endoscopic endpoints, we aimed to describe rates of mucosal healing in pediatric patients being treated with VDZ and examine the influence of anti‐TNF on outcomes.

Methods:

We conducted a retrospective review of all IBD patients ⩽21 years of age who initiated VDZ and underwent endoscopy. Primary outcome was mucosal healing (composite of endoscopic [SES‐CD] and Mayo score UC) and histological remission [Nancy index‐UC and Crohn disease (CD) histologic activity]. Descriptive statistics summarized the data. Comparisons were made for endpoints based on anti‐TNF exposure using univariate testing.

Results:

Sixty‐eight patients were included in the final analysis; 35 with UC and 33 with CD. Thirty‐two patients (22 UC and 10 CD) were anti‐TNF‐naïve and 36 patients (13 UC and 23 CD) were anti‐TNF‐exposed. The median duration on VDZ before endoscopic assessment was 49 (IQR 32–73) weeks. A total of 38% (25/66) of patients met the primary outcome of mucosal healing and did not differ between anti‐TNF‐naïve or anti‐TNF‐exposed. Endoscopic remission was achieved by 51% with significantly more anti‐TNF naïve patients reaching this endpoint (66% vs 40%, P = 0.03). Histologic remission was achieved by 42% of patients with a nonsignificant trend towards improved histologic remission rates in anti‐TNF‐naïve patients (52% vs 33%, P = 0.13).

Conclusions:

VDZ is associated with mucosal healing in pediatric IBD. Anti‐TNF exposure significantly impacted endoscopic remission, but not histologic remission in children on VDZ.
The Independent Relationships of Metacognition, Mindfulness, and Cognitive Insight to Self-Compassion in Schizophrenia
Authors: Hochheiser Jesse , Lundin Nancy B. , Lysaker Paul H.
Published: November 2019

The debilitating nature of psychosis may be exacerbated by societal stigma and feelings of social isolation over and above positive (e.g., hallucinations) and negative (e.g., flat affect) symptoms. Thus, recovery may be facilitated by increasing self-compassion, the ability to respond with a nonjudgmental attitude of kindness toward oneself as a result of connecting with one's own inadequacies and suffering. We conducted a stepwise regression in individuals with schizophrenia-spectrum disorders (n = 92) to determine the unique contributions of cognitive variables in predicting self-compassion, such as metacognition (the ability to form complex and integrated ideas about oneself and others), mindfulness, and cognitive insight. Results indicated that increased metacognitive awareness of others and mindfulness uniquely predicted greater self-compassion (i.e., self-kindness), whereas increased cognitive insight predicted greater lack of self-compassion (i.e., self-judgment). These findings suggest the potential for mindfulness and metacognitive interventions to increase positive self-compassion and promote recovery in psychosis.
Examining the Overlap Between Moral Injury and PTSD in US Veterans and Active Duty Military
Authors: Koenig Harold G. , Youssef Nagy A. , Ames Donna , Teng Ellen J. , Hill Terrence D.
Published: November 2019

Moral injury (MI) is a syndrome thought to be separate from posttraumatic stress disorder (PTSD), yet having some overlap. To determine the overlap, we examined the relationship between MI and the four DSM-5 PTSD symptom clusters (B, C, D, E) in US veterans and active duty military (ADM). The 45-item Moral Injury Symptom Scale (MISS-M) was administered to 591 veterans and ADM who had served in a combat theater and had PTSD symptoms. PTSD symptoms were measured with the PTSD Symptom Checklist-5, which assesses the four PTSD symptom clusters. Total MISS-M scores were more strongly associated with PTSD symptom cluster D (negative cognitions and emotions) in both bivariate and multivariate analyses. Findings for a 10-item version of the MISS-M (MISS-M-SF) closely followed those of the MISS-M. Although the overlap between MI and PTSD occurs to some extent across all PTSD symptoms clusters, the largest overlap tends to be with the negative cognitions and emotions cluster.
Toxoplasmosis in a Cohort of Italian Patients With Bipolar and Psychotic Disorders
Authors: Del Grande Claudia , Schiavi Elisa , Masci Isabella , Barbuti Margherita , Maccariello Giuseppe , Massimetti Gabriele , Bruschi Fabrizio , Dell'Osso Liliana
Published: November 2019

This study investigated the seroprevalence of Toxoplasma gondii in a cohort of 101 Italian inpatients affected by mood or schizophrenia-spectrum disorders and compared clinical features between seronegative and seropositive subjects. Patients diagnosed according to DSM-5 criteria underwent clinical assessments and blood collection to test parasite-specific IgG/IgM serum levels. Twenty-eight patients (27.7%) had IgG anti–T. gondii, and none had IgM antibodies. We found higher prevalence rate in patients aged 40 years or older, as compared with younger. No significant association was detected between T. gondii and a specific diagnostic category; however, bipolar disorder (BD)-II showed the highest positivity rate (40.9%). The seropositive status was significantly associated with a lower presence of psychotic symptoms, higher number of total episodes of predominant excitatory polarity, longer illness duration, and lower severity of current episode, particularly anxiety, depressive, and withdrawal/retardation symptoms. These preliminary results seem to point out an association between chronic toxoplasmosis and a specific subtype of BD.
Investigating Fetal Growth Restriction and Perinatal Risks in Appropriate for Gestational Age Infants: Using Cohort and Within-Sibling Analyses
Authors: Cnattingius S. , Kramer M. S. , Norman M. , Ludvigsson J. F. , Fang F. , Lu D.
Published: November 2019

(Abstracted from BJOG 2019;126(7):842–850)

Fetal growth restriction, defined as fetal growth below expectations, is statistically measured by a cutoff of birthweight for gestational age. Small-for-gestational-age (SGA) birth, however, is not always linked with fetal growth restriction: SGA infants may have reached their growth potential and just be small, while larger, non-SGA infants sometimes fail to reach their growth potential.
Neonatal Outcomes of Live Births After Blastocyst Biopsy in Preimplantation Genetic Testing Cycles: A Follow-up of 1721 Children
Authors: He Hui , Jing Shuang , Lu Chang Fu , Tan Yue Qiu , Luo Ke Li , Zhang Shuo Ping , Gong Fei , Lu Guang Xiu , Lin Ge
Published: November 2019

(Abstracted from Fertil Steril 2019;112:82–88)

Blastocyst biopsy as a means of preimplantation genetic testing (PGT) continues to increase in popularity and might provide a greater number of viable cells per biopsy compared with cleavage-stage biopsy. The increased number of testable cells enables the application of comprehensive chromosome screening modalities including next-generation sequencing, as well as the combination of multiple genetic tests.
Clearance of Mycoplasma genitalium Infection With Moxifloxacin in the Presence of Quinolone Resistance–Associated Mutations
Authors: Conway Ruairi James Harwood , Cook Seamus , Malone Cassandra , Bone Simon , Hassan-Ibrahim Mohammed Osman , Soni Suneeta
Published: November 2019

We present 2 cases of Mycoplasma genitalium infection that were successfully treated with moxifloxacin despite the presence of quinolone resistance–associated mutations in these strains.
Characteristics Associated With Presence of Pediatric Mental Health Care Policies in Emergency Departments
Authors: Cree Robyn A. , So Marvin , Franks Jessica , Richards Rachel , Leeb Rebecca , Hashikawa Andrew , Krug Steven , Ludwig Lorah , Olson Lenora M.
Published: November 2019

Objectives

The majority of US children do not have access to an emergency department (ED) with a pediatric mental health care policy in place. Our objective was to understand factors associated with whether US EDs have a pediatric mental health care policy.

Methods

We analyzed data from the National Pediatric Readiness Project, a nationally representative cross-sectional survey of US EDs. Nurse managers reported whether their hospitals had a policy to care for children with social/mental health concerns (n = 3612). We calculated prevalence estimates, prevalence ratios (PRs), and confidence intervals (CIs) for regional and ED characteristics (eg, rurality and types of personnel) by whether EDs had a pediatric mental health care policy.

Results

Overall, 46.2% (n = 1668/3612) of EDs had a pediatric mental health care policy. Emergency departments located in remote areas were 60% less likely to have such a policy compared with EDs in urban areas (PR, 0.4; CI, 0.3–0.5). Emergency department characteristics associated with having a pediatric mental health care policy included having a policy to transfer children with social/mental health concerns (PR, 5.4; CI, 4.7–6.2), having a policy to address maltreatment (PR, 3.4; CI, 2.6–4.4), and having nurse and physician pediatric emergency care coordinators (PR, 1.6; CI, 1.5–1.8).

Conclusions

Lower prevalence of pediatric mental health policies in rural EDs is concerning considering EDs are often the first point of contact for pediatric patients. This work highlights the importance of pediatric emergency care coordinators in fostering ED capacity to meet children's mental health needs.
Sternocleidomastoid Tendinopathy in a Pediatric Athlete
Authors: Chen Boqing , Yae Sophia , Delbert Matthew , Stitik Todd , Foye Patrick
Published: November 2019

To our knowledge, this case report describes the first known case of sternocleidomastoid tendinopathy, occurring in a pediatric athlete who had gone undiagnosed for a period of 2 yrs. She presented to our pain clinic with bilateral otalgia, occipital headaches, and occasional bouts of tinnitus and dizziness. An extensive workup by otolaryngology (ENT) including computed tomography imaging of the head, ear pressure equalization, and an attempt at therapeutic tonsillectomy left her with no diagnosis and no symptom relief. A clinical diagnosis of sternocleidomastoid tendinopathy was made at the initial visit based on history and physical examination findings, after excluding other diagnoses. Conservative treatment with physical therapy, acupuncture, and a short course of meloxicam and gabapentin resulted in total symptom resolution. This case is a unique reminder to clinicians that head, neck, and ear pain may precipitate from musculoskeletal origins. It emphasizes the importance of understanding local anatomy, obtaining a thorough history, and performing a detailed physical examination in arriving at an accurate diagnosis.
Association of Participation in the American Board of Physical Medicine and Rehabilitation Maintenance of Certification Program and Physician Disciplinary Actions
Authors: Kinney Carolyn L. , Raddatz Mikaela M. , Sliwa James A. , Driscoll Sherilyn W. , Robinson Lawrence R.
Published: November 2019

Objective

The study analyzed the relationship between participation in the American Board of Physical Medicine and Rehabilitation maintenance of certification program and the incidence of disciplinary actions by state medical boards over a physician’s career. The hypothesis is that physicians who do not maintain their board certification have a higher likelihood of state medical board disciplinary actions.

Design

This retrospective cohort study analyzed American Board of Physical Medicine and Rehabilitation maintenance of certification data from all board-certified physiatrists who were enrolled in the American Board of Physical Medicine and Rehabilitation maintenance of certification program from 1993 to 2007.

Results

Matching examination and license data were available for 4794 physicians, who received a total of 212 disciplinary action reports through the Federation of State Medical Boards. The results showed that physicians who have a lapse in completing the American Board of Physical Medicine and Rehabilitation maintenance of certification program have a 2.5-fold higher incidence of receiving a disciplinary action report through the Federation of State Medical Boards (95% confidence interval = 1.76–3.63) and had higher severity violations (χ2 = 7.14, P < 0.05) than physicians whose certificate never lapsed.

Conclusions

For physicians in physical medicine and rehabilitation, loss of board certification through failure to fulfill the maintenance of certification program requirements is associated with an increased risk of disciplinary action from a state medical licensing board.
Association of Copeptin With Sense of Coherence in Individuals With Varying Degrees of Glucose Intolerance
Authors: Madhu Sri Venkata , Aslam Mohammad , Siddiqui Azaz Ahmad , Goyal Sandeep , Mishra Brijesh Kumar
Published: November 2019

Objective

This study aimed to examine the association of serum copeptin levels, a surrogate marker of arginine-vasopressin secretion with sense of coherence (SOC) among individuals with varying degrees of glucose intolerance.

Methods

The study was conducted in 120 age- and sex-matched individuals who were divided equally into three groups. Group A included individuals with normal glucose tolerance; group B, individuals with prediabetes (impaired glucose tolerance and/or impaired fasting glucose); and group C, individuals with newly detected diabetes mellitus (NDDM). SOC, perceived stress scale (PSS), copeptin, anthropometry, glycated hemoglobin, insulin, and salivary cortisol were measured in all study participants.

Results

The SOC score was found to be significantly lower in group C compared with group A (p < .001) and group B (p = .006). The PSS score was found to be significantly higher in group C compared with group A (p = .002). No significant difference was found between PSS scores of groups B and C (p = .25). Copeptin levels were found to be significantly higher in group C compared with group A (p = .016). Copeptin levels in group C did not differ significantly from those in group B (p = .056). There was a significant negative correlation between serum copeptin levels and SOC in the NDDM group C (r = 0.31, p = .048) and overall (r = 0.19, p = .037). In multiple regression analysis, SOC emerged as the variable with the strongest association with 2-hour postprandial plasma glucose and glycated hemoglobin.

Conclusion

Individuals with NDDM displayed significantly higher serum copeptin levels that inversely correlated with SOC, a global measure of stress coping ability.
Hospital Admissions Associated With Medication-Related Problems in Thai Older Patients: A Multicenter Prospective Observational Study
Authors: Dechanont Supinya , Jedsadayanmata Arom , Butthum Bodin , Kongkaew Chuenjid
Published: November 2019

Objective

The aim of the study was to estimate the prevalence rate and risk factors of medication-related problems (MRPs) leading to hospital admissions in Thai older patients.

Methods

A prospective observational study was carried out in nine hospitals in Lower Northern Thailand. Participants admitted to internal medicine units were screened for suspected MRPs by clinical pharmacists using medical record review and patient interview. Three experts evaluated suspected MRPs independently using the following four criteria: contribution of MRPs to hospital admissions, causality, severity, and preventability.

Results

Of 1776 patients admitted during the study period, 56 patients (3.2%) were deemed to have causal MRPs; 24 (42.9%) were judged as preventable. The medication groups most commonly associated with MRPs were those targeting the endocrine system, especially antidiabetic medications, such as metformin and glipizide. Preventable MRPs were usually manifest as hypoglycemia (n = 15, 62.5%). The variables that contributed to hospital admissions associated with MRPs were age (odds ratio = 1.92; 95% confidence interval [CI] = 1.06–3.47), starting a new drug within 1 week (odds ratio = 2.31; 95% CI = 1.08–4.95), or within 1 month (odds ratio = 2.17; 95% CI = 1.05–4.48).

Conclusions

Hospital admissions associated with MRPs in Thai older patients continue to burden the Thai healthcare system of which nearly half were preventable. Further studies should consider analysis of costs and include hepatic and renal function status of participants.
A comparison between the TEG 6s and TEG 5000 analyzers to assess coagulation in trauma patients
Authors: Neal Matthew D. , Moore Ernest E. , Walsh Mark , Thomas Scott , Callcut Rachael A. , Kornblith Lucy Z. , Schreiber Martin , Ekeh Akpofure Peter , Singer Adam J. , Lottenberg Lawrence , Foreman Michael , Evans Susan , Winfield Robert D. , Goodman Michael D. , Freeman Carl , Milia David , Saillant Noelle , Hartmann Jan , Achneck Hardean E.
Published: November 2019

BACKGROUND

Trauma-induced coagulopathy is a major driver of mortality following severe injury. Viscoelastic goal-directed resuscitation can reduce mortality after injury. The TEG 5000 system is widely used for viscoelastic testing. However, the TEG 6s system incorporates newer technology, with encouraging results in cardiovascular interventions. The purpose of this study was to validate the TEG 6s system for use in trauma patients.

METHODS

Multicenter noninvasive observational study for method comparison conducted at 12 US Levels I and II trauma centers. Agreement between the TEG 6s and TEG 5000 systems was examined using citrated kaolin reaction time (CK.R), citrated functional fibrinogen maximum amplitude (CFF.MA), citrated kaolin percent clot lysis at 30 minutes (CK.LY30), citrated RapidTEG maximum amplitude (CRT.MA), and citrated kaolin maximum amplitude (CK.MA) parameters in adults meeting full or limited trauma team criteria. Blood was drawn ≤1 hour after admission. Assays were repeated in duplicate. Reliability (TEG 5000 vs. TEG 6s analyzers) and repeatability (interdevice comparison) was quantified. Linear regression was used to define the relationship between TEG 6s and TEG 5000 devices.

RESULTS

A total of 475 patients were enrolled. The cohort was predominantly male (68.6%) with a median age of 49 years. Regression line slope estimates (ß) and linear correlation estimates (p) were as follows: CK.R (ß = 1.05,ρ= 0.9), CFF.MA (ß = 0.99,ρ= 0.95), CK.LY30 (ß = 1.01,ρ= 0.91), CRT.MA (TEG 6s) versus CK.MA (TEG 5000) (ß = 1.06,ρ= 0.86) as well as versus CRT.MA (TEG 5000) (ß = 0.93,ρ= 0.93), indicating strong reliability between the devices. Overall, within-device repeatability was better for TEG 6s versus TEG 5000, particularly for CFF.MA and CK.LY30.

CONCLUSION

The TEG 6s device appears to be highly reliable for use in trauma patients, with close correlation to the TEG 5000 device and equivalent/improved within-device reliability. Given the potential advantages of using the TEG 6s device at the site of care, confirmation of agreement between the devices represents an important advance in diagnostic testing.

LEVEL OF EVIDENCE

Diagnostic test, level II.
Sound sequences in birdsong: how much do birds really care?
Authors: Fishbein Adam R. , Idsardi William J. , Ball Gregory F. , Dooling Robert J.
Published: November 2019

The complex and melodic nature of many birds' songs has raised interest in potential parallels between avian vocal sequences and human speech. The similarities between birdsong and speech in production and learning are well established, but surprisingly little is known about how birds perceive song sequences. One popular laboratory songbird, the zebra finch (Taeniopygia guttata), has recently attracted attention as an avian model for human speech, in part because the male learns to produce the individual elements in its song motif in a fixed sequence. But psychoacoustic evidence shows that adult zebra finches are relatively insensitive to the sequential features of song syllables. Instead, zebra finches and other birds seem to be exquisitely sensitive to the acoustic details of individual syllables to a degree that is beyond human hearing capacity. Based on these findings, we present a finite-state model of zebra finch perception of song syllable sequences and discuss the rich informational capacity of their vocal system. Furthermore, we highlight the abilities of budgerigars (Melopsittacus undulatus), a parrot species, to hear sequential features better than zebra finches and suggest that neurophysiological investigations comparing these species could prove fruitful for uncovering neural mechanisms for auditory sequence perception in human speech.

This article is part of the theme issue ‘What can animal communication teach us about human language?’
Some cautions regarding the phonological continuity hypothesis
Authors: Idsardi William J.
Published: November 2019

We consider the Phonological Continuity Hypothesis (PCH) of Fitch (2018) in light of a broader range of formal systems. A consideration of the learning and generalization of simple patterns such as AAB from Marcus (Marcus 2000Curr. Dir.9, 145–147(doi:10.1111/1467-8721.00080)) shows that finite-state automata defined in the standard way fail to generalize in a compatible fashion. However, pushdown automata with finite-memory limits do show compatible generalization capabilities. The third class of formal systems—tree automata—provide yet another possibility for the processing of words within sentences. We conclude that there are additional possible formal differences between sound patterns and sentence patterns, which will make testing the PCH even more difficult.

This article is part of the theme issue ‘What can animal communication teach us about human language?’
O-antigen biosynthesis gene clusters of Escherichia albertii: their diversity and similarity to Escherichia coli gene clusters and the development of an O-genotyping method
Authors: Ooka Tadasuke , Seto Kazuko , Ogura Yoshitoshi , Nakamura Keiji , Iguchi Atsushi , Gotoh Yasuhiro , Honda Mikiko , Etoh Yoshiki , Ikeda Tetsuya , Sugitani Wakana , Konno Takayuki , Kawano Kimiko , Imuta Naoko , Yoshiie Kiyotaka , Hara-Kudo Yukiko , Murakami Koichi , Hayashi Tetsuya , Nishi Junichiro
Published: November 2019

Escherichia albertii

is a recently recognized human enteropathogen that is closely related to

Escherichia coli

. In many Gram-negative bacteria, including

E. coli

, O-antigen variation has long been used for the serotyping of strains. In

E. albertii

, while eight O-serotypes unique to this species have been identified, some strains have been shown to exhibit genetic or serological similarity to known

E. coli

/

Shigella

O-serotypes. However, the diversity of O-serotypes and O-antigen biosynthesis gene clusters (O-AGCs) of

E. albertii

remains to be systematically investigated. Here, we analysed the O-AGCs of 65

E. albertii

strains and identified 40

E. albertii

O-genotypes (EAOgs) (named EAOg1–EAOg40). Analyses of the 40 EAOgs revealed that as many as 20 EAOgs exhibited significant genetic and serological similarity to the O-AGCs of known

E. coli

/

Shigella

O-serotypes, and provided evidence for the inter-species horizontal gene transfer of O-AGCs between

E. albertii

and

E. coli

. Based on the sequence variation in the wzx gene among the 40 EAOgs, we developed a multiplex PCR-based O-genotyping system for

E. albertii

(EAO-genotyping PCR) and verified its usefulness by genotyping 278

E. albertii

strains from various sources. Although 225 (80.9 %) of the 278 strains could be genotyped, 51 were not assigned to any of the 40 EAOgs, indicating that further analyses are required to better understand the diversity of O-AGCs in

E. albertii

and improve the EAO-genotyping PCR method. A phylogenetic view of

E. albertii

strains sequenced so far is also presented with the distribution of the 40 EAOgs, which provided multiple examples for the intra-species horizontal transfer of O-AGCs in

E. albertii

.
Prediction of GPI-Anchored proteins with pointer neural networks
Authors: Gíslason Magnús Halldór , Nielsen Henrik , Almagro Armenteros José Juan , Johansen Alexander Rosenberg
Published: November 2019

GPI-anchors constitute a very important post-translational modification, linking many proteins to the outer face of the plasma membrane in eukaryotic cells. Since experimental validation of GPI-anchoring signals is slow and costly, computational approaches for predicting them from amino acid sequences are needed. However, the most recent GPI predictor is more than a decade old and considerable progress has been made in machine learning since then. We present a new dataset and a novel method, NetGPI, for GPI signal prediction. NetGPI is based on recurrent neural networks, incorporating an attention mechanism that simultaneously detects GPI-anchoring signals and points out the location of their ω-sites. The performance of NetGPI is superior to existing methods with regards to discrimination between GPI-anchored proteins and other secretory proteins and approximate (±1 position) placement of the ω-site.

NetGPI is available at: https://services.healthtech.dtu.dk/service.php?NetGPI

The code repository is available at: https://github.com/mhgislason/netgpi-1.1
A new genome allows the identification of genes associated with natural variation in aluminium tolerance in Brachiaria grasses
Authors: Worthington Margaret , Perez Juan Guillermo , Mussurova Saule , Silva-Cordoba Alexander , Castiblanco Valheria , Jones Charlotte , Fernandez-Fuentes Narcis , Skot Leif , Dyer Sarah , Tohme Joe , Di Palma Federica , Arango Jacobo , Armstead Ian , De Vega Jose J
Published: November 2019

Toxic concentrations of aluminium cations and low phosphorus availability are the main yield-limiting factors in acidic soils, which represent half of the potentially available arable land. Brachiaria grasses, which are commonly sown as a forage in the tropics because of their resilience and low demand for nutrients, have a greater tolerance to high concentrations of aluminium cations than most other grass crops. In this work, we explored the natural variation in tolerance to aluminium cations (Al3+) between high and low tolerant Brachiaria species and characterised their transcriptional differences during stress. We also identified three QTLs associated with root vigour during Al3+ stress in their hybrid progeny. By integrating these results with a new Brachiaria reference genome, we have identified 30 genes responsible for Al3+ tolerance in Brachiaria. We also observed differential expression during stress of genes involved in RNA translation, response signalling, cell wall composition and vesicle location genes homologous to aluminium-induced proteins involved in limiting uptake or localizing the toxin. However, there was limited regulation of malate transporters in Brachiaria, which are associated with external tolerance mechanisms to Al3+ stress in other grasses. The contrasting regulation of RNA translation and response signalling suggests response phasing is critical to Al3+ tolerance.

HIGHLIGHT

We identified QTLs, genes and molecular responses in high and low tolerant Brachiaria grasses associated with aspects of response to aluminium stress, such as regulation, cell-wall composition and active transport.
Robust banded protoxylem pattern formation through microtubule-based directional ROP diffusion restriction
Authors: Jacobs Bas , Molenaar Jaap , Deinum Eva E.
Published: November 2019

In plant vascular tissue development, different cell wall patterns are formed, offering different mechanical properties optimised for different growth stages. Critical in these patterning processes are Rho of Plants (ROP) proteins, a class of evolutionarily conserved small GTPase proteins responsible for local membrane domain formation in many organisms. While the spotted metaxylem pattern can easily be understood as a result of a Turing-style reaction-diffusion mechanism, it remains an open question how the consistent orientation of evenly spaced bands and spirals as found in protoxylem is achieved. We hypothesise that this orientation results from an interaction between ROPs and an array of transversely oriented cortical microtubules that acts as a directional diffusion barrier. Here, we explore this hypothesis using partial differential equation models with anisotropic ROP diffusion and show that a horizontal microtubule array acting as a vertical diffusion barrier to active ROP can yield a horizontally banded ROP pattern. We then study the underlying mechanism in more detail, finding that it can only orient curved pattern features but not straight lines. This implies that, once formed, banded and spiral patterns cannot be reoriented by this mechanism. Finally, we observe that ROPs and microtubules together only form ultimately static patterns if the interaction is implemented with sufficient biological realism.
A genetic map of the response to DNA damage in human cells
Authors: Olivieri Michele , Cho Tiffany , Álvarez-Quilón Alejandro , Li Kejiao , Schellenberg Matthew J. , Zimmermann Michal , Hustedt Nicole , Rossi Silvia Emma , Adam Salomé , Melo Henrique , Heijink Anne Margriet , Sastre-Moreno Guillermo , Moatti Nathalie , Szilard Rachel , McEwan Andrea , Ling Alexanda K. , Serrano-Benitez Almudena , Ubhi Tajinder , Delgado-Sainz Irene , Ferguson Michael W. , Brown Grant W. , Cortés-Ledesma Felipe , Williams R. Scott , Martin Alberto , Xu Dongyi , Durocher Daniel
Published: November 2019

The response to DNA damage is critical for cellular homeostasis, tumor suppression, immunity and gametogenesis. In order to provide an unbiased and global view of the DNA damage response in human cells, we undertook 28 CRISPR/Cas9 screens against 25 genotoxic agents in the retinal pigment epithelium-1 (RPE1) cell line. These screens identified 840 genes whose loss causes either sensitivity or resistance to DNA damaging agents. Mining this dataset, we uncovered that ERCC6L2, which is mutated in a bone-marrow failure syndrome, codes for a canonical non-homologous end-joining pathway factor; that the RNA polymerase II component ELOF1 modulates the response to transcription-blocking agents and that the cytotoxicity of the G-quadruplex ligand pyridostatin involves trapping topoisomerase II on DNA. This map of the DNA damage response provides a rich resource to study this fundamental cellular system and has implications for the development and use of genotoxic agents in cancer therapy.
Physiological responses to light explain competition and facilitation in a tree diversity experiment
Authors: Kothari Shan , Montgomery Rebecca , Cavender-Bares Jeannine
Published: November 2019

Ecologists often invoke interspecific facilitation to help explain positive biodiversity-ecosystem function relationships in plant communities, but seldom test how it occurs. One mechanism through which one species may facilitate another is by ameliorating abiotic stress. Physiological experiments show that a chronic excess of light can cause stress that depresses carbon assimilation. If shading by a plant’s neighbors reduces light stress enough, it may facilitate that plant’s growth. If light is instead most often a limiting factor for photosynthesis, shading may have an adverse, competitive effect.

In a temperate tree diversity experiment, we measured stem growth rates and photosynthetic physiology in broadleaf trees across a gradient of light availability imposed by their neighbors. At the extremes, trees experienced nearly full sun (monoculture), or were shaded by nearby fast-growing conifers (shaded biculture).

Most species had slower growth rates with larger neighbors, implying a net competitive effect. On the other hand, the two most shade-tolerant species (Tilia americanaandAcer negundo) and the most shade-intolerant one (Betula papyrifera) had faster stem growth rates with larger neighbors. The two most shade-tolerant species had large increases in photoinhibition (reduced dark-acclimated Fv/Fm) across the gradient of increasing light availability, which suggests they are more vulnerable to chronic light stress. While most species had lower carbon assimilation rates in the shaded biculture treatment,T. americanahad rates up to 25% higher.T. americanaalso dropped its leaves 3-4 weeks earlier in monocultures, curtailing its growing season. We conclude that although large neighbors can cause light limitation in shade-intolerant species, they can also increase growth through abiotic stress amelioration in shade-tolerant species. Finally, in shade-intolerantB. papyrifera, we find a pattern of stem elongation in trees with larger neighbors, which may suggest that a shade avoidance response accounts for the apparent positive trend in stem volume.

Synthesis: Both positive and negative species interactions in our experiment can be explained in large part by the photosynthetic responses of trees to the light environment created by their neighbors. We show that photosynthetic physiology can help explain the species interactions that underlie biodiversity-ecosystem function relationships. The insights that ecologists gain by searching for such physiological mechanisms may help us forecast species interactions under environmental change.
Cultivar-specific transcriptome and pan-transcriptome reconstruction of tetraploid potato
Authors: Petek Marko , Zagorščak Maja , Ramšak Živa , Sanders Sheri , Tomaž Špela , Tseng Elizabeth , Zouine Mohamed , Coll Anna , Gruden Kristina
Published: November 2019

Although the reference genome ofSolanum tuberosumGroup Phureja double-monoploid (DM) clone is available, knowledge on the genetic diversity of the highly heterozygous tetraploid Group Tuberosum, representing most cultivated varieties, remains largely unexplored. This lack of knowledge hinders further progress in potato research. In conducted investigation, we first merged and manually curated the two existing partially-overlapping DM genome-based gene models, creating a union of genes in Phureja scaffold. Next, we compiled available and newly generated RNA-Seq datasets (cca. 1.5 billion reads) for three tetraploid potato genotypes (cultivar Désirée, cultivar Rywal, and breeding clone PW363) with diverse breeding pedigrees. Short-read transcriptomes were assembled using severalde novoassemblers under different settings to test for optimal outcome. For cultivar Rywal, PacBio Iso-Seq full-length transcriptome sequencing was also performed. EvidentialGene redundancy-reducing pipeline complemented with in-house developed scripts was employed to produce accurate and complete cultivar-specific transcriptomes, as well as to attain the pan-transcriptome. The generated transcriptomes and pan-transcriptome represent a valuable resource for potato gene variability exploration, high-throughput omics analyses, and breeding programmes.
Effects of advanced age upon astrocyte-specific responses to acute traumatic brain injury in mice
Authors: Early Alexandria N. , Gorman Amy A. , Van Eldik Linda J. , Bachstetter Adam D. , Morganti Josh M.
Published: November 2019

Background

Older-age individuals are at the highest risk for disability from a traumatic brain injury (TBI). Astrocytes are the most numerous glia in the brain, necessary for brain function, yet there is little known about unique responses of astrocytes in the aged-brain following TBI.

Methods

Our approach examined astrocytes in young adult, 4-month-old, versus aged, 18-month-old mice, at 1, 3, and 7 days post-TBI. We selected these time points to span the critical period in the transition from acute injury to presumably irreversible tissue damage and disability. Two approaches were used to define the astrocyte contribution to TBI by age interaction: 1) tissue histology and morphological phenotyping, and 2) transcriptomics on enriched astrocytes from the injured brain.

Results

Aging was found to have a profound effect on the TBI-induced loss of homeostatic astrocyte function needed for maintaining water transport and edema – namely, aquaporin-4. The loss of homoeostatic responses was coupled with a progressive exacerbation of astrogliosis in the aged brain as a function of time after injury. Moreover, clasmatodendrosis, an underrecognized astrogliopathy, was found to be significantly increased in the aged brain, but not in the young brain. As a function of TBI, we observed a transitory refraction in the number of these astrocytes, which rebounded by 7 days post-injury in the aged brain. The transcriptomics found disproportionate changes in genes attributed to reactive astrocytes, inflammatory response, complement pathway, and synaptic support in aged mice following TBI compared to young mice. Additionally, our data highlight that TBI did not evoke a clear alignment with previously defined “A1/A2” dichotomy of reactive astrogliosis.

Conclusions

Overall, our findings point toward a progressive phenotype of aged astrocytes following TBI that we hypothesize to be maladaptive, shedding new insights into potentially modifiable astrocyte-specific mechanisms that may underlie increased fragility of the aged brain to trauma.
Molecular epidemiology of Escherichia coli producing CTX-M and plasmid AmpC-type β-lactamases from dairy farms identifies a dominant plasmid encoding CTX-M-32 but no evidence for transmission to humans in the same geographical region
Authors: Findlay Jacqueline , Mounsey Oliver , Lee Winnie W.Y. , Newbold Nerissa , Morley Katy , Schubert Hannah , Gould Virginia C. , Cogan Tristan A. , Reyher Kristen K. , Avison Matthew B.
Published: November 2019

Third-generation cephalosporin resistance (3GC-R) in Escherichia coli is a rising problem in human and farmed animal populations. We conducted whole genome sequencing analysis of 138 representative 3GC-R isolates previously collected from dairy farms in South West England and confirmed by PCR to carry acquired 3GC-R genes. This analysis identified blaCTX-M (131 isolates: encoding CTX-M-1, −14, −15, −32 and the novel variant, CTX-M-214), blaCMY-2 (6 isolates) and blaDHA-1 (one isolate). A highly conserved plasmid was identified in 73 isolates, representing 27 E. coli sequence types. This novel ~220 kb IncHI2 plasmid carrying blaCTX-M-32 was sequenced to closure and designated pMOO-32. It was found experimentally to be stable in cattle and human transconjugant E. coli even in the absence of selective pressure and was found by multiplex PCR to be present on 26 study farms representing a remarkable range of transmission over 1500 square kilometres. However, the plasmid was not found amongst human urinary E. coli we have recently characterised from people living in the same geographical location, collected in parallel with farm sampling. There were close relatives of two blaCTX-M plasmids circulating amongst eight human and two cattle isolates, and a closely related blaCMY-2 plasmid found in one cattle and one human isolate. However, phylogenetic evidence of recent sharing of 3GC-R strains between farms and humans in the same region was not found.

Importance

Third-generation cephalosporins (3GCs) are critically important antibacterials and 3GC-resistance (3GC-R) threatens human health, particularly in the context of opportunistic pathogens such as Escherichia coli. There is some evidence for zoonotic transmission of 3GC-R E. coli through food, but little work has been done examining possible transmission (e.g. via interaction of people with the local near-farm environment). We characterised acquired 3GC-R E. coli found on dairy farms in a geographically restricted region of the United Kingdom and compared these with E. coli from people living in the same region, collected in parallel. Whilst there is strong evidence for recent farm-to-farm transmission of 3GC-R strains and plasmids – including one epidemic plasmid that has a remarkable capacity to transmit – there was no evidence that 3GC-R found on study farms had a significant impact on circulating 3GC-R E. coli strains or plasmids in the local human population.
Recombination and selection against introgressed DNA
Authors: Veller Carl , Edelman Nathaniel B. , Muralidhar Pavitra , Nowak Martin A.
Published: November 2019

DNA introgressed from one species into another is typically deleterious at many genomic loci in the recipient species. It is therefore purged by selection over time. Here, we use mathematical modeling and whole-genome simulations to study the influence of recombination on the purging of introgressed DNA. We find that aggregate recombination controls the genome-wide rate of purging in the first few generations after admixture, when purging is most rapid. Aggregate recombination is quantified by, the average recombination rate across all locus pairs, and analogous metrics. It is influenced by the number of crossovers (i.e., the map length) and their locations along chromosomes, and by the number of chromosomes and heterogeneity in their size. A comparative prediction of our analysis is that species with fewer chromosomes should purge introgressed DNA more profoundly, and therefore should exhibit a weaker genomic signal of historical introgression. With regard to patterns across the genome, we show that, in heterogametic species with autosomal recombination in both sexes, more purging is expected on sex chromosomes than on autosomes, all else equal. The opposite prediction holds for species without autosomal recombination in the heterogametic sex. Finally, we show that positive genomic correlations between local recombination rate and introgressed ancestry, as recently observed in several taxa, are likely driven not by recombination’s effect in unlinking neutral from deleterious introgressed alleles, but rather by its effect on the rate of purging of the deleterious alleles themselves.

Note on this version

An earlier version of this manuscript had two parts: (1) Calculations of the variance of genetic relatedness between individuals with particular pedigree relationships, taking into account the randomness of recombination and segregation in their pedigree. (2) An investigation of the rate of purging of introgressed DNA following admixture, based in part on results from part (1). Part (1) has since been published as Veller et al. (2020). The present manuscript has been reconfigured to focus on part (2).
Individual kinetochore-fibers locally dissipate force to maintain robust mammalian spindle structure
Authors: Long Alexandra F. , Suresh Pooja , Dumont Sophie
Published: November 2019

At cell division, the mammalian kinetochore binds many spindle microtubules that make up the kinetochore-fiber. To segregate chromosomes, the kinetochore-fiber must be dynamic and generate and respond to force. Yet, how it remodels under force remains poorly understood. Kinetochore-fibers cannot be reconstitutedin vitro, and exerting controlled forcesin vivoremains challenging. Here, we use microneedles to pull on mammalian kinetochore-fibers and probe how sustained force regulates their dynamics and structure. We show that force lengthens kinetochore-fibers by persistently favoring plus-end polymerization, not by increasing polymerization rate. We demonstrate that force suppresses depolymerization at both plus- and minus-ends, rather than sliding microtubules within the kinetochore-fiber. Finally, we observe that kinetochore-fibers break but do not detach from kinetochores or poles. Together, this work suggests an engineering principle for spindle structural homeostasis: different physical mechanisms of local force dissipation by the k-fiber limit force transmission to preserve robust spindle structure. These findings may inform how other dynamic, force-generating cellular machines achieve mechanical robustness.
Improved protein structure prediction using predicted inter-residue orientations
Authors: Yang Jianyi , Anishchenko Ivan , Park Hahnbeom , Peng Zhenling , Ovchinnikov Sergey , Baker David
Published: November 2019

The prediction of inter-residue contacts and distances from co-evolutionary data using deep learning has considerably advanced protein structure prediction. Here we build on these advances by developing a deep residual network for predicting inter-residue orientations in addition to distances, and a Rosetta constrained energy minimization protocol for rapidly and accurately generating structure models guided by these restraints. In benchmark tests on CASP13 and CAMEO derived sets, the method outperforms all previously described structure prediction methods. Although trained entirely on native proteins, the network consistently assigns higher probability tode novodesigned proteins, identifying the key fold determining residues and providing an independent quantitative measure of the “ideality” of a protein structure. The method promises to be useful for a broad range of protein structure prediction and design problems.