bluuebunny/crossref_metadata_2025 huggingface dataset:
Pregabalin vs placebo to prevent chronic pain after whiplash injury in at-risk individuals: results of a feasibility study for a large randomised controlled trial
Authors: Nikles Jane , Keijzers Gerben , Mitchell Geoffrey , Farrell Scott F. , Perez Siegfried , Schug Stephan , Ware Robert S. , McLean Samuel A. , Connelly Luke B. , Sterling Michele
Published: June 2021

There are few effective treatments for acute whiplash-associated disorders (WADs). Early features of central sensitisation predict poor recovery. The effect of pregabalin on central sensitisation might prevent chronic pain after acute whiplash injury. This double blind, placebo-controlled randomised controlled trial examined feasibility and potential effectiveness of pregabalin compared with placebo for people with acute WAD. Twenty-four participants with acute WAD (<48 hours) and at risk of poor recovery (pain ≥5/10) were recruited from hospital emergency departments in Queensland, Australia, and randomly assigned by concealed allocation to either pregabalin (n = 10) or placebo (n = 14). Pregabalin was commenced at 75 mg bd, titrated to 300 mg bd for 4 weeks, and then weaned over 1 week. Participants were assessed at 5 weeks and 3, 6, and 12 months. Feasibility issues included recruitment difficulties and greater attrition in the placebo group. For the primary clinical outcome of neck pain intensity, attrition at 5 weeks was pregabalin: 10% and placebo: 36% and at 12 months was pregabalin: 10% and placebo: 43%. Pregabalin may be more effective than placebo for the primary clinical outcome of neck pain intensity at 3 months (mean difference: −4.0 [95% confidence interval −6.2 to −1.7]) on an 11-point Numerical Rating Scale. Effects were maintained at 6 months but not 12 months. There were no serious adverse events. Minor adverse events were more common in the pregabalin group. A definitive large randomised controlled trial of pregabalin for acute whiplash injury is warranted. Feasibility issues would need to be addressed with modifications to the protocol.
Gastric Hyperplastic Polyps Can Shrink After Discontinuation of Proton Pump Inhibitors
Authors: Nikaido Mitsuhiro , Miyamoto Shin’ichi , Utsumi Takahiro , Shimizu Takahiro , Nakanishi Yuki , Kumagai Ken , Teramura Mari , Setoyama Takeshi , Seno Hiroshi
Published: June 2021

Goal:

This study investigated whether gastric hyperplastic polyps (GHPs) shrink after discontinuation of proton pump inhibitor (PPI) alone.

Background:

Long-term use of PPIs has been reported to increase the incidence of GHPs, which sometimes bleed and cause anemia. We experienced a patient whose recurrent hemorrhagic GHPs associated with long-term use of PPIs had disappeared after discontinuation of PPIs.

Study:

This study was conducted retrospectively at Kyoto University Hospital. Patients with histologically confirmed GHPs who had been taking PPIs for >6 months and who had undergone a repeat endoscopy within 2 years were included. Polyp shrinkage was defined as the disappearance of polyps or a reduction of >50% in the long diameter of the largest polyp.

Results:

Six patients who discontinued PPIs were compared with 17 patients who continued PPIs. Polyp shrinkage was significantly more frequent in the PPI-discontinuation group (5/6, 83%) than in the PPI continuation group (0/17, 0%) (P<0.001). In 2 patients in the PPI-discontinuation group, the polyps completely disappeared finally.

Conclusion:

These findings suggest that discontinuation of PPIs can shrink GHPs in patients using PPIs.
Does Women’s Screening History Have Any Impact on Mammography Screening Attendance After Tailored Education?
Authors: Brevik Thea B. , Tropé Ameli , Laake Petter , Bjørkly Stål
Published: June 2021

Background:

Many ethnic minority women have low attendance at breast cancer screening.

Objectives:

This brief report explores whether women’s screening histories impact mammography screening attendance after tailored education.

Research Design:

Systematic searches were conducted in 5 databases. Randomized controlled trials of educational interventions tailored to ethnic minority women that measured attendance at mammography screening were eligible for inclusion. Data extraction and risk of bias assessment were performed independently. Data were combined in a meta-analysis by using random effects models. Heterogeneity was estimated by using I
2 statistics.

Results:

Six studies with 3521 women were eligible for inclusion. The D+L pooled risk ratio (RR) for mammography attendance for never screened participants was 1.54 (95% confidence interval, 1.24–1.91; P<0.001), with low heterogeneity (I
2=27.1%, P=0.231). The D+L pooled risk ratio for attendance for ever screened participants was 1.26 (95% confidence interval, 1.11–1.43; P<0.001), with low heterogeneity (I
2=35.5%, P=0.213).

Conclusions:

Tailored education increased attendance at mammography by 54% among never screened women and 26% among ever screened women. Although these findings must be interpreted with caution, the findings suggest that women’s screening history is an important and ignored variable that affects how effective tailored education is on mammography screening attendance.
A Collaborative Intervention Between Emergency Medicine and Infectious Diseases to Increase Syphilis and HIV Screening in the Emergency Department
Authors: Lipps Ashley A. , Bazan Jose A. , Lustberg Mark E. , Sobhanie Mohammad Mahdee , Pollak Brandon , Nandam Kushal , Koletar Susan L. , Lindsey Sommer , Dick Michael , Malvestutto Carlos
Published: June 2021

Background

Sexually transmitted infections (STIs) are a common reason for evaluation in the emergency department (ED). Given the overlapping risk factors for STIs, patients screened for gonorrhea and chlamydia should be tested for syphilis and HIV. Syphilis and HIV testing rates in the ED have been reported to be low. The study objective was to examine whether collaboration between emergency medicine (EM) and infectious disease (ID) providers improved syphilis and HIV testing in the ED.

Methods

A multidisciplinary team of EM and ID providers was formed to identify and address barriers to syphilis and HIV testing in the ED. Syphilis, HIV, chlamydia, and gonorrhea testing and infection rates were calculated and compared during 2 time periods: preintervention (January 1, 2012–December 30, 2017) and postintervention (November 1, 2018–November 30, 2019). We also extracted clinical and laboratory data from patients with positive syphilis and HIV results during the study period.

Results

The most commonly cited barrier to syphilis and HIV testing was concern about follow-up of positive results. Compared with the preintervention period, syphilis and HIV testing rates increased significantly in the postintervention period (incidence rate ratios, 30.70 [P < 0.0001] and 28.99 [P < 0.0001] for syphilis and HIV, respectively). The postintervention period was also associated with a significant increase in the identification of patients with positive syphilis and HIV results (incidence rate ratios, 7.02 [P < 0.0001] and 2.34 [P = 0.03], respectively).

Conclusions

Collaboration between EM and ID providers resulted in a significant increase in syphilis and HIV testing and diagnosis in the ED.
Fumarate Hydratase Deficiency Should be Considered in the Differential Diagnosis of Uterine and Extrauterine Smooth Muscle Tumors of Uncertain Malignant Potential (STUMP)
Authors: Pors Jennifer , Weiel Julianna J. , Devereaux Kelly A. , Folkins Ann K. , Longacre Teri A.
Published: June 2021

Fumarate hydratase-deficient leiomyomas (dFH leiomyomas) often display atypical pathologic features yet exhibit a benign clinical course. Recent data suggest that dFH leiomyomas may be misclassified as smooth muscle tumors of uncertain malignant potential, a category that encompasses a heterogenous subgroup of uterine neoplasms with smooth muscle differentiation and atypical features that impart ambiguity regarding their expected clinical behavior. dFH leiomyomas can be seen in the context of hereditary leiomyomatosis and renal cell carcinoma syndrome or in the sporadic setting. In this retrospective study, we sought to examine the prevalence and clinicopathologic characteristics of dFH leiomyomas in 48 tumors previously diagnosed as smooth muscle tumors of uncertain malignant potential from 38 patients. Of these 48 tumors, 3 (6.3%) occurring in 2 patients were found to be deficient for FH by immunohistochemistry, including 1 uterine and 2 extrauterine (abdominopelvic) tumors. The 3 tumors showed histologic features typical of dFH leiomyomas, including hemangiopericytoma-like vessels, edema, macronucleoli, and atypia. Neither patient developed recurrent leiomyomas or renal cell carcinoma, and both were alive without disease at last follow-up. Our data suggest that dFH leiomyomas should be considered in the differential diagnosis of smooth muscle tumors of uncertain malignant potential, even in the context of extrauterine disease. Identification of FH deficiency in these tumors supports their classification as dFH leiomyomas despite their atypical morphologic features and/or clinical presentation. Importantly, detection of dFH in these cases may identify women at increased risk for hereditary leiomyomatosis and renal cell carcinoma who would benefit from genetic counseling and consideration for FH germline testing.
Age of red blood cells is not associated with in-hospital mortality in massively transfused patients
Authors: Saadah Nicholas H. , Wood Erica M. , Bailey Michael J. , Cooper D. James , French Craig J. , Haysom Helen E. , Sparrow Rosemary L. , Wellard Cameron J. , McQuilten Zoe K.
Published: June 2021

BACKGROUND

Studies comparing mortality following massive transfusion (MT) with fresher versus longer-stored red blood cells (RBCs) have focused on trauma patients. The Australian and New Zealand Massive Transfusion Registry collects data on all adult MT cases (≥5 RBCs within 4 hours, any bleeding context, ≥18 years) at participating hospitals.

METHODS

Years 2007 to 2018 data from 29 hospitals were analyzed to quantify the association between mortality and RBC storage time in adult MT cases. We ran three logistic regression models separately on each of seven bleeding contexts, with in-hospital mortality as the outcome and, in turn, (1) mean storage time (STmean) quartiles, (2) proportion of RBCs ≥30 days old (propOLD), and (3) scalar age of blood index as predictors.

RESULTS

A total of 8,685 adult MT cases involving transfusion of 126,622 RBCs were analyzed with Australian and New Zealand data analyzed separately. Mean storage times for these cases were (by quartile in ascending order) as follows: Australia, 12.5 days (range, 3.1–15.5 days), 17.7 (15.5–19.9), 22.3 (19.9–24.9), and 29.8 (24.9–41.7); New Zealand, 11.3 days (3.6–13.7), 15.3 (13.7–16.8), 18.7 (16.8–20.7), and 24.5 (20.7–35.6). The odds ratios comparing in-hospital mortality for each quartile with that of the control first quartile (freshest blood), proportion of longer-stored (≥30 days) RBCs, and scalar age of blood index were not statistically significant across all bleeding contexts.

CONCLUSION

We find no correlation between in-hospital mortality and storage time of transfused RBCs in a large cohort of adult MT patients representing all bleeding contexts. These results are consistent with those of recent large multicenter trials.

LEVEL OF EVIDENCE

Epidemiologic, level III; Therapeutic, level IV.
High occurrence of postintensive care syndrome identified in surgical ICU survivors after implementation of a multidisciplinary clinic
Authors: Bottom-Tanzer Samantha F. , Poyant Janelle O. , Louzada Maria T. , Ahmed Sana E. , Boudouvas Abbey , Poon Eileen , Hojman Horacio M. , Bugaev Nikolay , Johnson Benjamin P. , Van Kirk Anna Lisa , Daniel Eryn , Emoff Caroline , Mahoney Eric J.
Published: June 2021

BACKGROUND

Postintensive care syndrome (PICS) has been identified in a large proportion of medical intensive care unit survivors; however, the occurrence surgical intensive care unit (SICU) survivors is unknown. We implemented a multidisciplinary critical care outpatient clinic (CCOC) to identify the occurrence of PICS in SICU survivors.

METHODS

Seventy acute care surgery and trauma patients, 18 years or older, who remained in the SICU for 72 hours or longer at a Level I trauma center were seen in CCOC at 2 weeks, 12 weeks, and 24 weeks after hospital discharge. The CCOC staffing included a nurse coordinator, social worker, critical care pharmacist, physical therapist, and acute care surgeon who identified PICS sequelae in their respective specialties by clinical criteria and screening questionnaires.

RESULTS

Of 82 eligible patients, 70 (85.4%) were seen at least once for 116 total visits. Forty-three (61.4%) patients suffered traumatic injuries and 27 (38.6%) underwent emergent general surgery. Sixty-seven (95.7%) demonstrated at least one PICS criterion. Over all visits, 26 (37.1%) patients presented with one PICS criterion, 24 (34.3%) patients with two, and 17 (24.3%) with three. Cognitive impairment was observed in 29 (41.4%) patients, psychiatric in 30 (42.9%), and physical symptoms in 65 (92.9%). Activity Measure for Post-Acute Care scores improved from severe impairment at admission to full function by 12 weeks postdischarge, yet 6 Minute Walk Test scores remained below age-matched references through all visits. Patients expressed mild to moderate depression based on Patient Health Questionnaire-9 scores. A medication reconciliation was completed at 96.5% (112/116) of the visits with 116 total medication recommendations. By 24 weeks following discharge, only 26.4% (14/53) of previously employed patients had resumed work.

CONCLUSION

Through the successful implementation of a multidisciplinary CCOC, this study identifies an exorbitant rate of PICS among SICU survivors.

LEVEL OF EVIDENCE

Therapeutic/epidemiological, level III.
Does drainage or resection predict subsequent interventions and long-term quality of life in patients with Grade IV pancreatic injuries: A population-based analysis
Authors: Ball Chad G. , Biffl Walter L. , Vogt Kelly , Hameed S. Morad , Parry Neil G. , Kirkpatrick Andrew W. , Kaminsky Matthew
Published: June 2021

BACKGROUND

Clinical equipoise remains significant for the treatment of Grade IV pancreatic injuries in stable patients (i.e., drainage vs. resection). The literature is poor in regards to experience, confirmed main pancreatic ductal injury, nuanced multidisciplinary treatment, and long-term patient quality of life (QOL). The primary aim was to evaluate the management and outcomes (including long-term QOL) associated with Grade IV pancreatic injuries.

METHODS

All severely injured adult patients with pancreatic trauma (1995–2020) were evaluated (Grade IV injuries compared). Concordance of perioperative imaging, intraoperative exploration, and pathological reporting with a main pancreatic ductal injury was required. Patients with resection of Grade IV injuries were compared with drainage alone. Long-term QOL was evaluated (Standard Short Form-36).

RESULTS

Of 475 pancreatic injuries, 36(8%) were confirmed as Grade IV. Twenty-four (67%) underwent a pancreatic resection (29% pancreatoduodenectomy; 71% extended distal pancreatectomy [EDP]). Patient, injury and procedure demographics were similar between resection and drainage groups (p > 0.05). Pancreas-specific complications in the drainage group included 92% pancreatic leaks, 8% pseudocyst, and 8% walled-off pancreatic necrosis. Among patients with controlled pancreatic fistulas beyond 90 days, 67% required subsequent pancreatic operations (fistulo-jejunostomy or EDP). Among patients whose fistulas closed, 75% suffered from recurrent pancreatitis (67% eventually undergoing a Frey or EDP). All patients in the resection group had fistula closure by 64 days after injury. The median number of pancreas-related health care encounters following discharge was higher in the drainage group (9 vs. 5; p = 0.012). Long-term (median follow-up = 9 years) total QOL, mental and physical health scores were higher in the initial resection group (p = 0.031, 0.022 and 0.017 respectively).

CONCLUSION

The immediate, intermediate and long-term experiences for patients who sustain Grade IV pancreatic injuries indicate that resection is the preferred option, when possible. The majority of drainage patients will require additional, delayed pancreas-targeted surgical interventions and report poorer long-term QOL.

LEVEL OF EVIDENCE

Epidemiology/Prognostic, Level III.
Pregnancy, fertility concerns, and fertility preservation procedures in French breast cancer survivors in the FEERIC national study (on behalf of the Seintinelles research network)
Authors: Mangiardi-Veltin Manon , Sebbag Clara , Rousset-Jablonski Christine , Ray-Coquard Isabelle , Berkach Clémentine , Laot Lucie , Wang Yuting , Abdennebi Inès , Labrosse Julie , Sautter Camille , Toussaint Aullène , Sablone Laura , Laas Enora , Khallouch Sarah , Coussy Florence , Santulli Pietro , Chapron Charles , Bobrie Angelique , Jacot William , Sella Nadir , Dumas Elise , Sénéchal-Davin Claire , Espie Marc , Giacchetti Sylvie , Maitrot Lorraine , Plu-Bureau Geneviève , Coutant Charles , Guerin Julien , Asselain Bernard , Fumoleau Pierre , Rodrigues Manuel , Decanter Christine , Mailliez Audrey , Delrieu Lidia ,   Seintinelles research network, Reyal Fabien , Hamy Anne-Sophie
Published: June 2021

Objective

To study fertility concerns and oncofertility practices at time of breast cancer (BC) diagnosis.

Design

The FEERIC study (Fertility, Pregnancy, Contraception after BC in France) is a prospective, multicenter study.

Setting

Web-based collaborative research platform Seintinelles.

Patients

517 patients with prior BC diagnosis free from relapse and aged 18 to 43 years at inclusion (from 12th March 2018 to 27th June 2019).

Intervention

Baseline online self-administered questionnaires.

Main Outcome Measure

Fertility preservation procedures at BC diagnosis.

Results

Median age at BC diagnosis was 33.6 years and 424 patients (82.0%) received chemotherapy. Overall, 236 (45.6%) patients were offered specialized oncofertility counseling, 124 (24.0%) underwent one or more FP procedures with material preservation (oocytes n=108, 20.9%; embryos n=31, 6.0%; both oocytes and embryos n=13, 2.5%; ovarian cryopreservation n=6, 1.2%) and 78 patients received gonadotropin-releasing hormone agonists (15.1%). With a median follow-up of 26.7 months after the end of treatments,133 pregnancies (25.7%) had occurred in 85 patients (16.4%), including 20 unplanned pregnancies (15.0%). Most of the pregnancies were spontaneous (n=113, 87.6%), while 16 (12.4%) required medical interventions. Patients who had an unplanned pregnancy were less likely to have received fertility counseling (p=0.02) and contraceptive counseling (p=0.08) at BC diagnosis.

Conclusion

Most of the patients were not offered proper specialized oncofertility counseling at the time of BC diagnosis. Spontaneous pregnancies after BC were very much more frequent than pregnancies resulting from the use of cryopreserved gametes. Adequate contraceptive counseling seems as important as information about fertility and might prevent unplanned pregnancies.
Does reactogenicity after a second injection of the BNT162b2 vaccine predict spike IgG antibody levels in healthy Japanese subjects?
Authors: Takeuchi Masaaki , Higa Yukie , Esaki Akina , Nabeshima Yosuke , Nakazono Akemi
Published: June 2021

Adverse reactions are more common after the second injection of messenger RNA vaccines such as Pfizer/BioNTech’s BNT162b2. We hypothesized that the degree and severity of reactogenicity after the second injection reflects the magnitude of antibody production against the SARS CoV-2 virus spike protein (spike IgG). Blood samples were obtained from 67 healthy Japanese healthcare workers three weeks after the first injection and two weeks after the second injection of the BNT162b2 vaccine to measure spike IgG levels. Using questionnaires, we calculated an adverse event (AE) score (0-11) for each participant. The geometric mean of spike IgG titers increased from 1,047 antibody units (AU/mL) (95% CI: 855−1282 AU/mL) after the first injection to 17,378 AU/mL (14,622−20,663 AU/mL) after the second injection. The median AE score increased from 2 to 5. Spike IgG levels after the second injection were negatively correlated with age and positively correlated with spike IgG after the first injection. AE scores after the second injection were not significantly associated with log-transformed spike IgG after the second injection, when adjusted for age, sex, and log-transformed spike IgG after the first injection. Although the sample size was relatively small, reactogenicity after the second injection may not accurately reflect antibody production.
Developing and testing two arts-based knowledge translation tools for parents about pediatric acute gastroenteritis
Authors: Scott Shannon D. , Le Anne , Hartling Lisa
Published: June 2021

Characterized by vomiting, fever, abdominal pain and diarrhea, acute gastroenteritis (AGE) is a common illness in pediatric populations. In Canada, pediatric AGE accounts for 200,000 emergency visits, 20,000 hospital admissions, and 30 deaths a year. Yet, there continues to be significant practice variations in the treatment of AGE. Knowledge translation (KT) can help close the research-practice gap. In particular, art and stories are powerful mediums that cut across age, culture, language, literacy, and gender barriers.

The purpose of this study was to work with parents to develop an e-Book and whiteboard animation video for parents on pediatric AGE. Using a multi-method research process, we developed a 2 minute 57 second video and 39-page e-Book for pediatric AGE. Both tools underwent usability testing with parents in three Canadian emergency department waiting rooms in urban, rural, and remote regions. Focus groups were also conducted with parents in each of the three regions.

Overall, parents felt that digital and paper-based KT tools would be beneficial knowledge dissemination mediums. Our study showed that parents positively rated an e-Book and whiteboard animation video for pediatric AGE. These findings demonstrate how working together with key stakeholders can facilitate the development of KT tools for parents that are usable, relevant, and increase parental confidence. Furthermore, the type of KT tool developed is an important decision that may depend on parental preferences as well as when and where parents access the tools.

This report should be cited as

Scott, S.D., Le, A., Hartling, L. (2021). Developing and testing two arts-based knowledge translation tools for parents about pediatric acute gastroenteritis. Internal Technical Report. ECHO Research, University of Alberta.

Available at: http://www.echokt.ca/research/technical-reports/
Microbial communities network structure across strong environmental gradients: How do they compare to macroorganisms?
Authors: Arboleda-Baena C.M , Freilich M. A , Pareja C.B , Logares R , De la Iglesia R , Navarrete S.A
Published: June 2021

The way strong environmental gradients shape multispecific assemblages has allowed us to examine a suite of ecological and evolutionary hypotheses about structure, regulation, and community responses to fluctuating environments. But whether the highly diverse co-occurring, free-living microorganisms are shaped in similar ways as macroscopic organisms, across the same gradients, has yet to be addressed in most ecosystems. The ‘everything is everywhere’ hypothesis suggests they are not, at least not to the same extent. Here we characterize the structure of intertidal microbial biofilm communities and compare the intensity of zonation at the ‘species’ level, changes in taxonomic diversity and composition at the community level, and network attributes, with those observed in co-occurring macroalgae and invertebrates. At the level of species and OTUs, for dominant macro and microorganisms respectively, microbes showed less variability across the tidal gradient than macroorganisms. At the community-level, however, microbes and macro-organisms showed similarly strong patterns of tidal zonation, with major changes in composition and relative abundances across tides. Moreover, the proportion of ‘environmental specialists’ in different tidal zones was remarkably similar in micro and macroscopic communities, and taxonomic richness and diversity followed similar trends, with lower values in the high intertidal zone. Network analyses showed similar connectivity and transitivity, despite the large differences in absolute richness between the groups. A high proportion of positive co-occurrences within all tidal zones and mostly negative links between the high and low tidal zones were observed among habitat specialist taxa of micro-and macro-organisms. Thus, our results provide partial support to the idea that microbes are less affected by environmental variability than macroscopic counterparts. At the species-level, the most common microbe species exhibit less variation across tides than most common macroscopic organisms, suggesting the former perceive a more homogeneous environment and/or are more resistant to the associated stress. At the community-level, most indicators of community and network structure across the gradient are similar between microbes and macro-organisms, suggesting that despite orders of magnitude differences in richness and size, these two systems respond to stress gradients, giving rise to zonation patterns.
MP-NeRF: A Massively Parallel Method for Accelerating Protein Structure Reconstruction from Internal Coordinates
Authors: Alcaide Eric , Biderman Stella , Telenti Amalio , Maher M. Cyrus
Published: June 2021

The conversion of proteins between internal and cartesian coordinates is a limiting step in many pipelines, such as molecular dynamics simulations and machine learning models. This conversion is typically carried out by sequential or parallel applications of the Natural extension of Reference Frame (NeRF) algorithm. This work proposes a massively parallel NeRF implementation which, depending on the polymer length, achieves speedups between 400-1200x over the previous state-of-the-art. It accomplishes this by dividing the conversion into three main phases: parallel composition of the monomer backbone, assembly of backbone subunits, and parallel elongation of sidechains; and by batching these computations into a minimal number of efficient matrix operations. Special emphasis is placed on reusability and ease of use. We open source the code (available at https://github.com/EleutherAI/mp_nerf) and provide a corresponding python package.
A habitat class to land cover translation model for mapping Area of Habitat of terrestrial vertebrates
Authors: Lumbierres Maria , Dahal Prabhat Raj , Di Marco Moreno , Butchart Stuart H. M. , Donald Paul F. , Rondinini Carlo
Published: June 2021

Area of Habitat (AOH) is defined as the ‘habitat available to a species, that is, habitat within its range’ and is produced by subtracting areas of unsuitable land cover and elevation from the range. Habitat associations are documented using the IUCN Habitats Classification Scheme, and unvalidated expert opinion has been used so far to match habitat to land-cover classes generating a source of uncertainty in AOH maps. We develop a data-driven method to translate IUCN habitat classes to land-cover based on point locality data for 6,986 species of terrestrial mammals, birds, amphibians and reptiles. We extracted the land-cover class at each point locality and matched it to the IUCN habitat class(es) assigned to each species occurring there. Then we modelled each land cover class as a function of IUCN habitat using logistic regression models. The resulting odds ratios were used to assess the strength of the association of each habitat land-cover class. We then compared the performance of our data-driven model with those from a published expert knowledge translation table. The results show that some habitats (e.g. forest and desert) could be more confidently assigned to land-cover classes than others (e.g. wetlands and artificial). We calculated the association between habitat classes and land-cover classes as a continuous variable, but to map AOH, which is in the form of a binary presence/absence, it is necessary to apply a threshold of association. This can be chosen by the user according to the required balance between omission and commission errors. We demonstrate that a data-driven translation model and expert knowledge perform equally well, but the model provides greater standardization, objectivity and repeatability. Furthermore, this approach allows greater flexibility in the use of the results and allows uncertainty to be quantified. Our model can be developed regionally or for different taxonomic groups.
Reward influences the allocation but not the availability of resources in visual working memory
Authors: Brissenden James A. , Adkins Tyler J. , Hsu Yu Ting , Lee Taraz G.
Published: June 2021

Visual working memory possesses strict capacity constraints which place limits on the availability of resources for encoding and maintaining information. Studies have shown that prospective rewards improve performance on visual working memory tasks, but it remains unclear whether rewards increase total resource availability or rather influence the allocation of resources without affecting availability. Participants performed a continuous report visual working memory task with oriented grating stimuli. On each trial, participants were presented with a priority cue, which signaled the item most likely to be probed, and a reward cue, which signaled the magnitude of a performance-contingent reward. We showed that rewards decreased recall error for cued items and increased recall error for non-cued items. We further demonstrated that rewards produced a tradeoff in the probability of successfully encoding a cued versus a non-cued item rather than a tradeoff in recall precision or the probability of binding errors. Lastly, we showed that rewards only affected resource allocation when participants were given the opportunity to engage proactive control prior to encoding. These findings indicate that rewards influence the flexible allocation of resources during selection and encoding in visual working memory, but do not augment total capacity.
TrackSOM: mapping immune response dynamics through sequential clustering of time- and disease-course single-cell cytometry data
Authors: Putri Givanna H. , Chung Jonathan , Edwards Davis N. , Marsh-Wakefield Felix , Dervish Suat , Koprinska Irena , King Nicholas J.C. , Ashhurst Thomas M. , Read Mark N.
Published: June 2021

Mapping the dynamics of immune cell populations over time or disease-course is key to understanding immunopathogenesis and devising putative interventions. We present TrackSOM, an algorithm which delineates cellular populations and tracks their development over a time- or disease-course of cytometry datasets. We demonstrate TrackSOM-enabled elucidation of the immune response to West Nile Virus infection in mice, uncovering heterogeneous sub-populations of immune cells and relating their functional evolution to disease severity. TrackSOM is easy to use, encompasses few parameters, is quick to execute, and enables an integrative and dynamic overview of the immune system kinetics that underlie disease progression and/or resolution.
Stochastic fluctuations drive non-genetic evolution of proliferation in clonal cancer cell populations
Authors: Ortega-Sabater Carmen , Calvo Gabriel F. , Dinić Jelena , Podolski-Renic Ana , Pesic Milica , Pérez-García Víctor M.
Published: June 2021

Evolutionary dynamics allows us to understand many changes happening in a broad variety of biological systems, ranging from individuals to complete ecosystems. It is also behind a number of remarkable organizational changes that happen during the natural history of cancers. These reflect tumour heterogeneity, which is present at all cellular levels, including the genome, proteome and phenome, shaping its development and interrelation with its environment. An intriguing observation in different cohorts of oncological patients is that tumours exhibit an increased proliferation as the disease progresses, while the timescales involved are apparently too short for the fixation of sufficient driver mutations to promote an explosive growth. Here we discuss how phenotypic plasticity, emerging from a single genotype, may play a key role and provide a ground for a continuous acceleration of the proliferation rate of clonal populations with time. We address this question by combining the analysis of real time growth of non-small-cell lung carcinoma cells (line NCI-H460) together with stochastic and deterministic mathematical models that capture proliferation trait heterogeneity in clonal populations to elucidate the contribution of phenotypic transitions on tumour growth dynamics.
The cell adhesion molecule Sdk1 shapes assembly of a retinal circuit that detects localized edges
Authors: Rochon Pierre-Luc , Theriault Catherine , Olguin Aline Giselle Rangel , Krishnaswamy Arjun
Published: June 2021

Nearly 50 different mouse retinal ganglion cell (RGC) types sample the visual scene for distinct features. RGC feature selectivity arises from its synapses with a specific subset of amacrine (AC) and bipolar cell (BC) types, but how RGC dendrites arborize and collect input from these specific subsets remains poorly understood. Here we examine the hypothesis that RGCs employ molecular recognition systems to meet this challenge. By combining calcium imaging and type-specific histological stains we define a family of circuits that express the recognition molecule Sidekick 1 (Sdk1) which include a novel RGC type (S1-RGC) that responds to local edges. Genetic and physiological studies revealed that Sdk1 loss selectively disrupts S1-RGC visual responses which result from a loss of excitatory and inhibitory inputs and selective dendritic deficits on this neuron. We conclude that Sdk1 shapes dendrite growth and wiring to help S1-RGCs become feature selective.
MCGA: a multi-strategy conditional gene-based association framework integrating with isoform-level expression profiles reveals new susceptible and druggable candidate genes of schizophrenia
Authors: Li Xiangyi , Jiang Lin , Xue Chao , Li Mulin Jun , Li Miaoxin
Published: June 2021

Linkage disequilibrium and disease-associated variants in non-coding regions make it difficult to distinguish truly associated genes from redundantly associated genes for complex diseases. In this study, we proposed a new conditional gene-based framework called MCGA that leveraged an improved effective chi-squared statistic to control the type I error rates and remove the redundant associations. MCGA initially integrated two conventional strategies to map genetic variants to genes, i.e., mapping a variant to its physically nearby gene and mapping a variant to a gene if the variant is a gene-level expression quantitative trait locus (eQTL) of the gene. We further performed a simulation study and demonstrated that the isoform-level eQTL was more powerful than the gene-level eQTL in the association analysis. Then the third strategy, i.e., mapping a variant to a gene if the variant is an isoform-level eQTL of the gene, was also integrated with MCGA. We applied MCGA to predict the potential susceptibility genes of schizophrenia and found that the potential susceptibility genes identified by MCGA were enriched with many neuronal or synaptic signaling-related terms in the Gene Ontology knowledgebase and antipsychotics-gene interaction terms in the drug-gene interaction database (DGIdb). More importantly, nine susceptibility genes were the target genes of multiple approved antipsychotics in DrugBank. Comparing the susceptibility genes identified by the above three strategies implied that strategy based on isoform-level eQTL could be an important supplement for the other two strategies and help predict more candidate susceptibility isoforms and genes for complex diseases in a multi-tissue context.
Nuclear-cytoplasmic balance: whole genome duplications induce elevated organellar genome copy number
Authors: Gyorfy Matheus Fernandes , Miller Emma R. , Conover Justin L. , Grover Corrinne E. , Wendel Jonathan F. , Sloan Daniel B. , Sharbrough Joel
Published: June 2021

The plant genome is partitioned across three distinct subcellular compartments: the nucleus, mitochondria, and plastids. Successful coordination of gene expression among these organellar genomes and the nuclear genome is critical for plant function and fitness. Whole genome duplication events (WGDs) in the nucleus have played a major role in the diversification of land plants and are expected to perturb the relative copy number (stoichiometry) of nuclear, mitochondrial, and plastid genomes. Thus, elucidating the mechanisms whereby plant cells respond to the cytonuclear stoichiometric imbalance that follow WGDs represents an important yet underexplored question in understanding the evolutionary consequences of genome doubling. We used droplet digital PCR (ddPCR) to investigate the relationship between nuclear and organellar genome copy numbers in allopolyploids and their diploid progenitors in both wheat andArabidopsis. Polyploids exhibit elevated organellar genome copy numbers per cell, largely preserving the cytonuclear stoichiometry observed in diploids despite the change in nuclear genome copy number. To investigate the timescale over which cytonuclear stoichiometry may respond to WGD, we also estimated organellar genome copy number inArabidopsissynthetic autopolyploids and in a haploid-induced diploid line. We observed corresponding changes in organellar genome copy number in these laboratory-generated lines, indicating that at least some of the cellular response to cytonuclear stoichiometric imbalance is immediate following WGD. We conclude that increases in organellar genome copy numbers represent a common response to polyploidization, suggesting that maintenance of cytonuclear stoichiometry is an important component in establishing polyploid lineages.

Significance Statement

Whole genome duplications (WGD) have the potential to alter the stoichiometric balance between nuclear and organellar genomes. We used two separate diploid-polyploid complexes to show that plant cells with WGD exhibit elevated mitochondrial and plastid genome copy numbers, both immediately in lab-generated lines and in natural polyploids.
The benefits of herbivory outweigh the costs of bioerosion in a eutrophic coral community
Authors: Dytnerski James K. , Marshall Katie E. , Baker David M. , Russell Bayden D.
Published: June 2021

Herbivores play an integral part in maintaining the health of coral reefs by suppressing the growth of algae and accumulation of sediment and facilitating coral growth. However, in predator-depleted systems where densities of herbivores are unnaturally high, grazing can have detrimental effects on corals through excessive bioerosion. Yet, these benefits and costs are rarely investigated concurrently, especially in eutrophic systems where grazers may play a disproportionate role. We used a year-long exclusion experiment to elucidate the effect of natural densities of the dominant herbivore (the sea urchinDiadema setosum) on coral communities in a heavily fished and eutrophic system (Hong Kong, China). To assess benthic community response to grazing, we monitored the survival and growth of three locally abundant coral species (Pavona decussata, Platygyra carnosusandPoritessp.), algal and sediment accumulation, and bioerosion of coral skeletons across seasons. We found that urchins maintained our experimental coral assemblages, and when excluded, there was a 25 to 75-fold increase in algal-sediment matrix accumulation. Contrary to predictions, there was no general response of corals to urchin presence;Porites sp.survivorship increased whileP. decussatawas unaffected, and growth rates of both species was unchanged. Surprisingly,P. carnosusexperienced higher mortality and bioerosion of up to 33% of their buoyant weight when urchins were present. Therefore, under natural densities, sea urchins clear substrate of algae and sediment, increase survival, maintain growth rates and health of coral assemblages, yet can accelerate the bioerosion of species with porous skeletons following mortality.
Identification and differentiation of Pseudomonas species in field samples using an rpoD amplicon sequencing methodology
Authors: Lauritsen Jonas Greve , Hansen Morten Lindqvist , Bech Pernille Kjersgaard , Jelsbak Lars , Gram Lone , Strube Mikael Lenz
Published: June 2021

Species of the genus Pseudomonas are used for several biotechnological purposes, including plant biocontrol and bioremediation. To exploit the Pseudomonas genus in environmental, agricultural or industrial settings, the organisms must be profiled at species level as their bioactivity potential differs markedly between species. Standard 16S rRNA gene amplicon profiling does not allow for accurate species differentiation. Thus, the purpose of this study was to develop an amplicon-based high-resolution method targeting a 760 nt region of the rpoD gene enabling taxonomic differentiation of Pseudomonas species in soil samples. The method was benchmarked on a sixteen membered Pseudomonas species mock community. All 16 species were correctly and semi-quantitatively identified using rpoD gene amplicons, whereas 16S rRNA V3V4 amplicon sequencing only correctly identified one species. We analysed the Pseudomonas profile in thirteen soil samples in northern Zealand, Denmark, where samples were collected from grassland (3 samples) and agriculture soil (10 samples). Pseudomonas species represented up to 0.7% of the microbial community, of which each sampling site contained a unique Pseudomonas composition. Thirty culturable Pseudomonas strains were isolated from each grassland site and ten from each agriculture site and identified by Sanger sequencing of the rpoD gene. In all cases, the rpoD-amplicon approach identified more species than found by cultivation, including hard-to-culture non-fluorescent pseudomonads, as well as more than found by 16S rRNA V3V4 amplicon sequencing. Thus, rpoD profiling can be used for species profiling of Pseudomonas, and large scale prospecting of bioactive Pseudomonas may be guided by initial screening using this method.

Importance

A high throughput sequence-based method for profiling of Pseudomonas species in soil microbiomes was developed and identified more species than 16S rRNA gene sequencing or cultivation. Pseudomonas species are used as biocontrol organisms and plant-growth promoting agents, and the method will allow tracing of specific species of Pseudomonas as well as enable screening of environmental samples for further isolation and exploitation.
Enhanced virus translation enables miR-122-independent Hepatitis C Virus propagation
Authors: Panigrahi Mamata , Palmer Michael A , Wilson Joyce A
Published: June 2021

The 5’UTR of the Hepatitis C Virus genome forms RNA structures that regulate virus replication and translation. The region contains a viral internal ribosomal entry site and a 5’ terminal region. Binding of the liver specific miRNA, miR-122, to two conserved binding sites in the 5’ terminal region regulates viral replication, translation, and genome stability, and is essential for efficient virus replication, but its precise mechanism of its action is still under debate. A current hypothesis is that miR-122 binding stimulates viral translation by facilitating the viral 5’ UTR to form the translationally active HCV IRES RNA structure. While miR-122 is essential for detectable virus replication in cell culture, several viral variants with 5’ UTR mutations exhibit low level replication in the absence of miR-122. We show that HCV mutants capable of replicating independently of miR-122 also replicate independently of other microRNAs generated by the canonical miRNA synthesis pathway. Further, we also show that the mutant genomes display an enhanced translation phenotype that correlates with their ability to replicate independently of miR-122. Finally, we provide evidence that translation regulation is the major role for miR-122, and show that miR-122-independent HCV replication can be rescued to miR-122-dependent levels by the combined impacts of 5’ UTR mutations that stimulate translation, and by stabilizing the viral genome by knockdown of host exonucleases and phosphatases that degrade the genome. Thus, we provide a model suggesting that translation stimulation and genome stabilization are the primary roles for miR-122 in the virus life cycle.

IMPORTANCE

The unusual role of miR-122 in promoting HCV propagation is incompletely understood but is essential for an HCV infection. To better understand its role, we have analyzed HCV mutants capable of replicating independently of miR-122. Our data show that the ability of viruses to replicate independently of miR-122 correlates with enhanced virus translation, but that genome stabilization is required to restore efficient HCV replication. This suggests that viruses must gain both abilities to escape the need for miR-122 and impacts the possibility that HCV can evolve to replicate outside of the liver.
Synthetic Cooling Agents in US-marketed E-cigarette Refill Liquids and Popular Disposable E-cigarettes: Chemical Analysis and Risk Assessment
Authors: Jabba Sairam V. , Erythropel Hanno C. , Torres Deyri Garcia , Delgado Lauren A. , Woodrow Jackson G. , Anastas Paul T. , Zimmerman Julie B. , Jordt Sven-Eric
Published: June 2021

Background

Menthol, through its cooling and pleasant sensory effects, facilitates smoking and tobacco product initiation, resulting in the high popularity of mint/menthol-flavored E-cigarettes. More recently, E-cigarette vendors started marketing synthetic cooling agents as additives that impart a cooling effect but lack a characteristic minty odor. Knowledge about content of synthetic coolants in US-marketed E-cigarette products and associated health risks is limited.

Methods

E-liquid vendor sites were searched with the terms “koolada”, “kool/cool”, “ice”, or WS-3/WS-23, denoting individual cooling agents, and relevant refill E-liquids were purchased. “Ice” flavor varieties of Puffbar, the most popular disposable E-cigarette brand, were compared with non-”Ice” varieties. E-liquids were characterized, and synthetic coolants quantified using GC/MS. Margin of exposure (MOE), a risk assessment parameter, was calculated to assess the risk associated with synthetic coolant exposure from E-cigarette use.

Results

WS-3 was detected in 24/25 refill E-liquids analyzed. All Puffbar flavor varieties contained either WS-23 (13/14) or WS-3 (5/14), in both “Ice”- and non-”Ice” flavors. Modeling consumption of WS-3 from vaped E-liquids, resulted in MOEs below the safe margin of 100 for most daily use scenarios. MOEs for WS-23 were <100 for 10/13 Puffbar flavors in all use scenarios. Puffbar power specifications are identical to Juul devices.

Conclusions

Synthetic cooling agents (WS-3/WS-23) were present in US-marketed E-cigarettes, at levels that may result in consumer exposures exceeding safety thresholds set by regulatory agencies. Synthetic coolants are not only found in mint-or menthol-flavored products, but also in fruit- and candy-flavored products, including popular disposable E-cigarette products such as Puffbar.

Implications

Synthetic cooling agents are widely used in “kool/cool”- and “ice”-flavored E-liquids and in E-liquids without these labels, both as a potential replacement for menthol or to add cooling ‘notes’ to non-menthol flavors. These agents may be used to bypass current and future regulatory limits on menthol content in tobacco products, and not just E-cigarettes. Since synthetic cooling agents are odorless, they may not fall under the category of “characterizing flavor”, potentially circumventing regulatory measures based on this concept. Regulators need to consider the additional health risks associated with exposure to synthetic cooling agents.