bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for failure of temporary hemiepiphysiodesis in Blount disease: a systematic review
Authors: Fan Bensen , Zhao Caixia , Sabharwal Sanjeev
Published: February 2019

There is limited information regarding the use of temporary hemiepiphysiodesis for Blount disease. We performed a systematic review of patients treated for Blount disease using either extraperiosteal staples or plates to identify characteristics affecting clinical outcome, including the need for unplanned procedures. A total of 53 patients (63 bone segments) underwent temporary hemiepiphysiodesis at a mean age of 8.8 years (1.8–14.7 years). Overall, 32/63 (51%) segments achieved neutral mechanical axis and 31/63 (49%) underwent unplanned subsequent procedures, with or without a subsequent osteotomy. On the basis of the available heterogeneous data, neither age at index surgery nor the type of implant correlated with the need for unplanned additional surgeries.
Problematic Eating Behaviors Are More Prevalent in African American Women Who Are Overweight or Obese Than African American Women Who Are Lean or Normal Weight
Authors: Opichka Katelyn , Smith Chery , Levine Allen S.
Published: February 2019

Problematic eating behaviors such as overeating and loss of control over consumption can lead to obesity. Problematic eating behaviors among women of differing body mass indexes were explored through focus group methodology, the Palatable Eating Motives Scale (PEMS), and a taste test in a sample of low-income African American women (n = 45). Women who were overweight or obese (W-O/O) reported more problematic eating behaviors including eating in the absence of hunger, frequent overeating, and increased food thoughts than women who were lean or normal weight (W-L/N). The W-O/O appear to possess more problematic eating behaviors than W-L/N.
Quantitative Multimodal Assessment of Concussion Recovery in Youth Athletes
Authors: Howell David R. , Myer Gregory D. , Brilliant Anna , Barber Foss Kim , Meehan William P.
Published: February 2019

Objective:

To evaluate recovery trajectories among youth athletes with a concussion and healthy controls across different domains using a quantitative and multifaceted protocol.

Study Design:

Prospective repeated measures.

Participants:

Youth athletes diagnosed with a concussion between the ages of 8 and 18 years were evaluated (1) within 10 days after injury, (2) approximately 3 weeks after injury, and (3) after return-to-play clearance. Control participants completed the same protocol.

Setting:

Sport concussion clinic.

Interventions:

N/A.

Main Outcome Measures:

Participants underwent a multifaceted protocol that assessed symptoms (postconcussion symptom scale [PCSS]), dual-task gait, event-related potentials (ERPs), and eye tracking.

Results:

Sixty-seven athletes participated: 36 after concussion (age = 14.0 ± 2.6 years; 44% female) and 31 controls (age = 14.6 ± 2.2 years; 39% female). Concussion symptoms were higher for the concussion group compared with controls at the first (PCSS = 31.7 ± 18.8 vs 1.9 ± 2.9; P < 0.001) and second time points (PCSS = 10.8 ± 11.2 vs 1.8 ± 3.6; P = 0.001) but resolved by the final assessment (PCSS = 1.7 ± 3.6 vs 2.0 ± 3.8; P = 0.46). The concussion group walked slower during dual-task gait than controls at all 3 tests including after return-to-play clearance (0.83 ± 0.19 vs 0.95 ± 0.15 m/s; P = 0.049). There were no between-group differences for ERP connectivity or eye tracking. Those with concussions had a decrease in ERP connectivity recovery over the 3 time points, whereas control participants' scores increased (concussion Δ = −8.7 ± 28.0; control Δ = 13.9 ± 32.2; χ2 = 14.1, P = 0.001).

Conclusions:

Concussion is associated with altered dual-task gait speeds after resolution of concussion symptoms, but ERP and eye tracking measures did not demonstrate between-group differences across time. Some objective approaches to concussion monitoring may support with identifying deficits after concussion, but further work is required to delineate the role of gait, electrophysiological, and eye tracking methods for clinical decision-making.
Reimbursement Incentives to Improve Adherence to Follow-Up of Cervical Cancer Cytology Screening Results in Peru
Authors: Ferris Daron G. , Chen Jessica , Isaac Austin , Braithwaite Evan , Beideck Elena , Mikail Nima , Krotish Debra , Waller Jennifer L.
Published: February 2019

Objective

The purpose of this study was to determine Peruvian women's attitudes toward novel reimbursement incentives used to improve adherence to obtaining cervical cytology test results.

Materials and Methods

Women presenting for cervical cancer screening in Peru completed a 34-item Investigational Review Board-approved questionnaire. The questionnaire determined their attitudes toward various reimbursement incentives to improve adherence to obtaining cervical cytology results. Descriptive statistics, generalized linear models, and Kruskal-Wallis tests were used in the analyses.

Results

Completed questionnaires were available for 997 women. Most women (51%) would be more likely to return for their Pap result if an incentive was provided, 79% (759/956) agreed that they would pay for the Pap test, and 51% (402/859) would be willing to pay 10 Soles or less. Quechua-speaking women considered follow-up more difficult (p < .0001) but were less likely to return for their Pap results (p < .0001), pay for the Pap test (p < .0001), and afford paying more than 5 Soles (p < .0001) than women who spoke Spanish or both languages. More women who earn 1000 Soles/year or less would likely return if incentivized (p < .0001), felt the incentive would help them remember to return (p = .0047), and would be willing to pay whether there was a rebate (p = .010) as compared with women earning more money.

Conclusions

A reimbursement incentive program designed to improve follow-up of cervical cytology test results was acceptable to most Peruvian women. Such a behavioral-modifying program may improve patient follow-up after cervical cytology testing. Implementation may reduce the morbidity and mortality of cervical cancer in remote regions of the country.
Upper gastrointestinal hemorrhage is associated with poor outcomes among patients with acute cholangitis: a nationwide analysis
Authors: Bilal Mohammad , Tayyem Obada , Saraireh Hamzeh , Chowdhry Monica , Guturu Praveen , Abougergi Marwan S.
Published: February 2019

Objective

Acute cholangitis (AC) and upper gastrointestinal hemorrhage (UGIH) are common emergencies encountered by gastroenterologists. We aimed to evaluate the impact of UGIH on in-hospital mortality, morbidity and resource utilization among patients with AC.

Patients and methods

Adult admissions with a principal diagnosis of AC were selected from the National Inpatient Sample 2010–2014. The exposure of interest was significant UGIH (requiring red blood cell transfusion). The primary outcome was in-hospital mortality. Secondary outcomes were significant UGIH’s incidence, morbidity (shock, prolonged mechanical ventilation and total parenteral nutrition), and resource utilization (length of hospital stay and total hospitalization charges and costs). Confounders were adjusted for using propensity matching and multivariate regression analysis.

Results

A total of 50 375 admissions were included in the analysis, 747 of whom developed significant UGIH. After adjusting for confounders, the adjusted odds ratio (aOR) of in-hospital mortality for patients who developed UGIH was 7.1 (95% confidence interval: 2.1–23.9, P<0.01) compared with those who did not. Significant UGIH was associated with substantial increase in morbidity [shock: aOR: 4.1 (2.1–9.3), P<0.01, prolonged mechanical ventilation: aOR: 5.8 (2.2–12.4), P<0.01, total parenteral nutrition: aOR: 4.7 (1.9–10.7), P<0.01], and resource utilization [mean adjusted difference in: length of hospital stay: 7.01 (4.72–9.29), P<0.01 and total hospitalization charges: $81 818 ($58 109–$105 527), P<0.01 and costs: $25 230 ($17 805–$32 653), P<0.01]. Similar results were obtained using multivariate regression analysis.

Conclusion

Onset of significant UGIH among patients hospitalized with AC has a detrimental effect on in-hospital mortality, morbidity and resource utilization.
Prospective Detection of Germline Mutation of Fumarate Hydratase in Women With Uterine Smooth Muscle Tumors Using Pathology-based Screening to Trigger Genetic Counseling for Hereditary Leiomyomatosis Renal Cell Carcinoma Syndrome
Authors: Rabban Joseph T. , Chan Emily , Mak Julie , Zaloudek Charles , Garg Karuna
Published: February 2019

Pathology-based screening of uterine smooth muscle tumors (uSMT) for morphology suggestive of fumarate hydratase deficiency (FH-d morphology) has been proposed as a method to identify women at increased risk for hereditary leiomyomatosis renal cell carcinoma (HLRCC) syndrome. For 5 years our clinical diagnostic practice has evaluated all women with any type of uSMT for FH-d morphology (defined, at low magnification, as staghorn shaped blood vessels and alveolar pattern edema and, at high magnification, as tumor macronucleoli surrounded by a halo and cytoplasmic eosinophilic globules) and, when present, used the pathology report to advise genetic counseling to further evaluate for HLRCC syndrome. We now report the results of this prospective screening strategy, with emphasis on the incidence and clinicopathologic features of FH-d morphology in uSMT, the rate of patient uptake of referral to genetic counseling, and the results of genetic testing for FH germline mutation. Among 2060 women with a uSMT, FH-d morphology was reported in 1.4% (30 women). Ten women elected to undergo FH genetic testing and 6 of 10 (60%) had a FH germline mutation: 5 were pathogenic mutations and 1 was a mutation variant of unknown significance. Therefore, the screening program led to a confirmed genetic diagnosis of HLRCC syndrome in 0.24% of all women with any type of uSMT. The women with a pathogenic mutation were ages 24 to 40 years. Although the majority of leiomyoma with bizarre nuclei exhibited FH-d morphology, the uSMT were conventional leiomyomas with FH-d morphology in 2 of 5 women found to have a pathogenic FH germline mutation. Relying on an abnormal FH immunostain result to trigger genetic counseling referral would have resulted in 2 of 5 (40%) cases with pathogenic FH germline mutation but normal FH immunoexpression going undetected, both of which were missense type mutations. There was no difference in the incidence of pathogenic FH germline mutation between FH-d morphology uSMT with an abnormal versus a normal FH immunostain result. Overall, this study demonstrates that prospective morphology-based screening, integrated with referral for genetic counseling, can result in the diagnosis of HLRCC syndrome in otherwise unselected women with uSMT. We conclude that this strategy should be incorporated in the routine pathologic examination of all uterine smooth muscle tumors.
Comparison of the efficacy of a bougie and stylet in patients with endotracheal intubation: A meta-analysis of randomized controlled trials
Authors: Sheu Yu-Jia , Yu Sung-Wei , Huang Tsai-Wei , Liu Feng-Lin , Lin Yen-Kuang , Tam Ka-Wai
Published: February 2019

BACKGROUND

Endotracheal intubation (ETI) is a procedure widely performed for several clinical indications. In typical ETI, an endotracheal tube is placed into a patient's trachea with the help of a malleable metal rod covered with a clear plastic sheath (called a stylet). However, another intubation aid, a bougie (also named a gum elastic bougie or endotracheal tube introducer), was also introduced in the clinical setting to improve the efficacy of conventional ETI.

METHODS

This study performed a systematic review and meta-analysis of randomized controlled trials to compare the efficacy of bougie and stylet approaches in ETI. PubMed, Embase, and Cochrane Library databases were searched for studies published before November 2018. Randomized controlled trials comparing the clinical outcomes of bougie and stylet approaches in patients who underwent orotracheal intubation were included. Meta-analyses were conducted by using a random effects model, and treatment efficacy was measured by evaluating the first-attempt success rate and intubation duration.

RESULTS

A total of 5 randomized controlled trials and 1,038 patients were included. Although a bougie resulted in a better first-attempt success rate, no significant difference was observed between the approaches (risk ratios, 1.03; 95% confidence interval, 0.85–1.24). Moreover, no significant differences were observed in the intubation duration and esophageal intubation rate between the bougie and stylet approaches.

CONCLUSION

Endotracheal intubation performed with a bougie was not superior over ETI performed with a stylet. Therefore, intubation approaches should be selected by considering personal preference and clinician expertise.

LEVEL OF EVIDENCE

Systematic review and meta-analysis, level II.
Structure and function of a trauma intensive care unit: A report from the Trauma Intensive Care Unit Prevalence Project
Authors: Michetti Christopher P. , Fakhry Samir M. , Brasel Karen , Martin Niels D. , Teicher Erik J. , Liu Chang , Newcomb Anna
Published: February 2019

BACKGROUND

Specialized trauma intensive care unit (TICU) care impacts patient outcomes. Few studies describe where and how TICU care is delivered. We performed an assessment of TICU structure and function at a sample of US trauma center TICUs.

METHODS

This was a multicenter study in which participants supplied information about their trauma centers, staff, clinical protocols, processes of care, and study TICU (the ICU admitting the majority of trauma patients).

RESULTS

Forty-five Level I trauma centers trauma centers enrolled through the American Association for the Surgery of Trauma multi-institutional trials platform; 71.1% had less than 750 beds and 55.5% treated 1,000 to 2,999 trauma activations/year. The median number of hospital ICU beds was 109 [66–185]. 46.7% were “closed” ICUs, 20% were “open,” and 82.2% had mandatory intensivist consultation. 42.2% ICUs were classified as trauma (≥80% of patients were trauma), 46.7% surgical/trauma, and 11.1% medical-surgical. Trauma ICUs had a median 10 [7–12] intensivists. Intensivists were present 24 hours/day in 80% of TICUs. Centers reported a median of 8 (interquartile range [IQR], 6–10) full-time trauma surgeons, whose ICU duties comprised 25% (IQR, 20%–40%) of their clinical time and 20% (IQR, 20–33) of total work time. A median 16 (IQR, 12–23) ICU beds in use were staffed by 10 (IQR, 7–14) nurses. There was considerable variation in the number and type of protocols used and in diagnostic methods for ventilator-associated pneumonia. Daily patient care checklists were used by 80% of ICUs. While inclusion of families on rounds was performed in 91.1% of ICUs, patient- and family-centered support programs were less common.

CONCLUSION

A study of structure and function of TICUs at a sample of Level I trauma centers revealed that presence of nontrauma patients was common, critical care is a significant component of trauma surgeons' professional practice, and significant variation exists in care delivery models and protocol use. Opportunities may exist to improve care through sharing of best practices.

LEVEL OF EVIDENCE

Therapeutic/Care management, level IV.
Nondisjunction and unequal spindle organization accompany the drive ofAegilops speltoidesB chromosomes
Authors: Wu DanDan , Ruban Alevtina , Fuchs Jörg , Macas Jiri , Novák Petr , Vaio Magdalena , Zhou YongHong , Houben Andreas
Published: February 2019

Supernumerary B chromosomes (Bs), which are often preferentially inherited, deviating from usual Mendelian segregation. This chromosome drive is one of the most important features of Bs. Here we analyzed the drive mechanism ofAegilops speltoidesBs and provide direct insight into its cellular mechanism. Comparative genomics resulted in the identification of the tandem repeat AesTR-183 ofAe. speltoidesBs, which also can be found on the Bs ofAe. muticaand rye, was used to track Bs during microgametogenesis. Nondisjunction of CENH3-positive, tubulin interacting B sister chromatids and an asymmetric spindle during first pollen grain mitosis are likely components of the accumulation process. A quantitative flow cytometric approach revealed, that independent on the number of Bs present in the mother plant Bs accumulate in the generative nuclei with more than 93%. Nine of eleven tested (peri)centromeric repeats were shared by A and B chromosomes. A common origin of the drive process inPoaceaeis likely.
Sox17expression in endocardium precursor cells regulates heart development in mice
Authors: Saba Rie , Kitajima Keiko , Rainbow Lucille , Engert Sylvia , Uemura Mami , Ishida Hidekazu , Kokkinopoulos Ioannis , Shintani Yasunori , Miyagawa Shigeru , Kanai Yoshiakira , Azuma-Kanai Masami , Koopman Peter , Meno Chikara , Kenny John , Lickert Heiko , Saga Yumiko , Suzuki Ken , Sawa Yoshiki , Yashiro Kenta
Published: February 2019

The endocardium is the endothelial component of the vertebrate heart and plays a key role in heart development. Cardiac progenitor cells (CPCs) that express the homeobox geneNkx2-5give rise to the endocardium. Where, when, and how the endocardium segregates during embryogenesis have remained largely unknown, however. We now show thatNkx2-5+CPCs that express the Sry-type HMG box geneSox17specifically differentiate into the endocardium in mouse embryos. Approximately 20% to 30% ofNkx2-5+CPCs transiently expressSox17from embryonic day (E) 7.5 to E8.5.AlthoughSox17is not essential or sufficient for endocardium fate, it can bias the fate of CPCs toward the endocardium. On the other hand,Sox17expression in the endocardium is required for heart development. Deletion ofSox17specifically in the mesoderm markedly impaired endocardium development with regard to cell proliferation and behavior. The proliferation of cardiomyocytes, ventricular trabeculation, and myocardium thickening were also impaired in a non–cell-autonomous manner in theSox17mutant, resulting in anomalous morphology of the heart, likely as a consequence of down-regulation of NOTCH signaling. Changes in gene expression profile in both the endocardium and myocardium preceded the reduction in NOTCH-related gene expression in the mutant embryos, suggesting thatSox17expression in the endocardium regulates an unknown signal required for nurturing of the myocardium. Our results thus provide insight into differentiation of the endocardium and its role in heart development.

Significance

The endocardium is vital for vertebrate heart development; however, the molecular mechanisms regulating fate determination and differentiation remain largely unknown. Here, we show that a part of the earliest cardiac progenitor cells (CPCs) transiently and exclusively expressSry-type HMG box geneSox17in the mouse embryo.Sox17-expressing CPCs specifically differentiate to the endocardium.Sox17biases the fate of CPCs toward the endocardium, and regulates proliferation and cellular behavior cell autonomously. Conversely,Sox17in the endocardium regulates the myocardium non-cell autonomously. Notably,Sox17is required for the ventricular trabeculation via the NOTCH signal that is not directly induced but maintained bySox17. This study, thus, sheds light on endocardium development.
The Genetic Basis of Transcriptional and Spatial Heterogeneity of Squamous Features in Pancreatic Ductal Adenocarcinoma
Authors: Hayashi Akimasa , Fan Jun , Chen Ruoyao , Ho Yu-jui , Makohon-Moore Alvin P. , Zhong Yi , Hong Jungeui , Sakamoto Hitomi , Attiyeh Marc A. , Kohutek Zachary A. , Zhang Lance , Huang Jinlong , Boumiza Aida , Kappagantula Rajya , Baez Priscilla , Wood Laura D. , Hruban Ralph H. , Marta Lisi , Chadalavada Kalyani , Nanjangud Gouri J. , Basturk Olca , Klimstra David S. , Overholtzer Michael , Iacobuzio-Donahue Christine A.
Published: February 2019

Recent studies indicate that pancreatic cancer expression profiles are variable and largely reflect a classical or basal-type phenotype. We performed genetic sequencing, RNA-seq, and histologic review of multiregion sampled pancreatic cancers and found that squamous and squamoid features, indicators of poor prognosis, correlate with a “basal-like” expressional type. Cancers with squamous features were more likely to have truncal mutations in chromatin modifier genes and intercellular heterogeneity for MYC amplification that was associated with entosis. In most patients the basal phenotype coexisted with a glandular component, and phylogenetic studies indicated that it arose from a subclonal population in the tumor. These data provide a unifying paradigm for understanding the interrelationship of basal-type features, squamous histology, and somatic mutations in chromatin modifier genes in the context of the clonal evolution of pancreatic cancer.
Thermal cycling-hyperthermia in combination with polyphenols, epigallocatechin gallate and chlorogenic acid, exerts synergistic anticancer effect against human pancreatic cancer PANC-1 cells
Authors: Lu Chueh-Hsuan , Chen Wei-Ting , Hsieh Chih-Hsiung , Kuo Yu-Yi , Chao Chih-Yu
Published: February 2019

Hyperthermia (HT) has shown feasibility and potency as an anticancer therapy. Administration of HT in the chemotherapy has previously enhanced the cytotoxicity of drugs against pancreatic cancer. However, the drugs used when conducting these studies are substantially conventional chemotherapeutic agents that may cause unwanted side effects. Additionally, the thermal dosage in the treatment of cancer cells could also probably harm the healthy cells. The purpose of this work was to investigate the potential of the two natural polyphenolic compounds, epigallocatechin gallate (EGCG) and chlorogenic acid (CGA), as heat synergizers in the thermal treatment of the PANC-1 cells. Furthermore, we have introduced a novel strategy entitled the thermal cycling-hyperthermia (TC-HT) that is capable of providing a maximum synergy and minimal side effect with the anticancer compounds. Our results demonstrate that the combination of the TC-HT and the CGA or EGCG markedly exerts the anticancer effect against the PANC-1 cells, while none of the single treatment induced such changes. The synergistic activity was attributed to the cell cycle arrest at the G2/M phase and the induction of the ROS-dependent mitochondria-mediated apoptosis. These findings not only represent the first thermal synergistic study of natural compounds in the treatment of pancreatic cancer, but also highlight the potential application of the TC-HT as an alternative strategy in anticancer treatment.
Microbiotyping the sinonasal microbiome
Authors: Bassiouni Ahmed , Paramasivan Sathish , Shiffer Arron , Dillon Matthew R , Cope Emily K , Cooksley Clare , Ali Mohammad Javed , Bleier Benjamin , Callejas Claudio , Cornet Marjolein E , Douglas Richard G , Dutra Daniel , Georgalas Christos , Harvey Richard J , Hwang Peter H , Luong Amber U , Schlosser Rodney J , Tantilipikorn Pongsakorn , Tewfik Marc A , Vreugde Sarah , Wormald Peter-John , Caporaso J Gregory , Psaltis Alkis J
Published: February 2019

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal ‘microbiotypes’ or ‘states’: the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based on geography. We also describe a potential reciprocal relationship between Corynebacterium species and Staphylococcus aureus, suggesting that a certain microbial equilibrium between various players is reached in the sinuses. We validate our approach by applying it to a separate 16S rRNA gene sequence dataset of 97 sinus swabs from a different patient cohort. Sinonasal microbiotyping may prove useful in reducing the complexity of describing sinonasal microbiota. It may drive future studies aimed at modeling microbial interactions in the sinuses and in doing so may facilitate the development of a tailored patient-specific approach to the treatment of sinus disease in the future.
Investigating on-road lane maintenance and speed regulation in post-stroke driving: a pilot case-control study
Authors: Zhou Heng , Sun Qian (Chayn) , Blane Alison , Hughes Brett , Falkmer Torbjörn , Xia Jianhong (Cecilia)
Published: February 2019

The post-stroke population is expected to rise and the cohort of post-stroke individuals who wish to return to driving is likely to rapidly increase too. Stroke can adversely affect coordination and judgement of drivers due to the executive dysfunction, which is relatively common in the post-stroke population but often undetected. Quantitatively examining vehicle control performance in post-stroke driving becomes essential to inspect whether and where post-stroke drivers are risky. To date, it is unclear as to which indicators, such as lane keeping or speed control, can differentiate driving performance of post-stroke drivers from that of normal (neurotypical) older drivers. By employing a case-control design using advanced vehicle movement tracking and analysis technology, this pilot study aimed to compare the variations in driving trajectory, lane keeping and speed control between the two groups using spatial and statistical techniques. The results showed that the mean Standard Deviation of Lane Deviation (SDLD) in post-stroke participants was higher than those of normal participants in complex driving tasks (U-turn and left turn) but almost the same in simple driving tasks (straight-line sections). No statistically significant differences were found in the speed maintenance between the post-stroke drivers and the normal adults. The findings indicate that, although older drivers can still drive as they need to after a stroke, the decline in cognitive abilities still imposes higher cognitive workload and more effort for post-stroke older drivers. Future studies can investigate post-stroke adults’ driving behaviour at more challenging driving scenarios, or design driving intervention program to improve their executive function in driving.
Identification of genetic markers for cortical areas using a Random Forest classification routine and the Allen Mouse Brain Atlas
Authors: Weed Natalie , Bakken Trygve , Graddis Nile , Gouwens Nathan , Millman Daniel , Hawrylycz Michael , Waters Jack
Published: February 2019

The mammalian neocortex is subdivided into a series of ‘cortical areas’ that are functionally and anatomically distinct, and are often distinguished in brain sections using histochemical stains and other markers of protein expression. We searched the Allen Mouse Brain Atlas, a database of gene expression, for novel markers of cortical areas. We employed a random forest algorithm to screen for genes that change expression at area borders. We found novel genetic markers for 19 of 39 areas and provide code that quickly and efficiently searches the Allen Mouse Brain Atlas.
Isolation and characterization of live yeast cells from ancient vessels as a tool in bio-archeology
Authors: Aouizerat Tzemach , Gutman Itai , Paz Yitzhak , Maeir Aren M. , Gadot Yuval , Gelman Daniel , Szitenberg Amir , Drori Elyashiv , Pinkus Ania , Schoemann Miriam , Kaplan Rachel , Ben-Gedalya Tziona , Coppenhagen-Glazer Shunit , Reich Eli , Saragovi Amijai , Lipschits Oded , Klutstein Michael , Hazan Ronen
Published: February 2019

Ancient fermented food has been studied based on recipes, residue analysis and ancient-DNA techniques and reconstructed using modern domesticated yeast. Here, we present a novel approach. We hypothesize that enriched yeast populations in fermented beverages could have become the dominant species in storage vessels and the descendants of these yeast could be isolated and studied long after. To this end, using a pipeline of yeast isolation from clay vessels developed here, we screened for yeast cells in beverage-related and non-related ancient vessels and sediments, from several archeological sites. We found that yeast cells could be successfully isolated specifically from clay containers of fermented beverages. Genomic analysis revealed that these yeast are similar to those found in traditional African beverages. Phenotypically, they grow similar to modern-beer producing yeast. Both strongly suggesting that they are descendants of the original fermenting yeast. These findings provide modern microorganisms as a new tool in bio-archeology.

Importance

So far, most of the study of ancient organisms was based mainly on the analysis of ancient DNA. Here we show that it is possible to isolate and study microorganisms, yeast in this case, from thousands of years old clay vessels, used for fermentation. We demonstrate that it is highly likely that these cells are descendants of the original yeast strains which participated in the fermentation process and were absorbed into the pottery vessels. Moreover, we characterize the isolated yeast their genome and the beer they produce. These results open new and exciting avenues in the study of domesticated microorganisms and contribute significantly to the fields of bio and experimental –archeology that aims to reconstruct ancient artifacts and products.
The successful invasion of the European earwig across North America reflects adaptations to thermal regimes but not mean temperatures
Authors: Tourneur Jean-Claude , Meunier Joël
Published: February 2019

Understanding the mechanisms by which an introduced species adapt to newly encountered habitats is a major question in ecology. A key method to address this question is to collect data on introduced species that have successfully invaded a broad diversity of novel environments, and analyze how their life-history traits changed with these new constraints. Here, we present and analyze such a unique data set in the European earwigForficula auriculariaL, an insect that invaded North America during the last century. We conducted a common garden experiment, in which we measured 13 life-history traits in 4158 individuals from 19 populations across North America. Our results demonstrate that the successful invasion of this species came with changes in 10 of their life-history traits in response to thermal regimes (winter-summer and autumn-spring temperatures), but with no change in response to the overall mean temperatures of the invaded locations. Importantly, we show that some of these changes are by-products of novel thermal regimes, whereas others reflect adaptive strategies of females to these constraints. Overall, our findings reveal the importance of thermal regimes over mean temperatures in climate adaptation, and emphasize that studying adaptive capabilities is crucial to predict the limits of biological invasions.
The pharmacodynamic inoculum effect from the perspective of bacterial population modeling
Authors: Baeder Desiree Y. , Regoes Roland R.
Published: February 2019

Synopsis

Background

The quantitative determination of the effects of antimicrobials is essential for our understanding of pharmacodynamics and for their rational clinical application. However, common pharmacodynamic measures of antimicrobial efficacy, such as the MIC and the pharmacodynamic function, fail to capture the observed dependence of efficacy on the bacterial population size — a phenomenon called inoculum effect.

Objectives

We aimed to assess the relationship between bacterial inoculum size and pharmacodynamic parameters, and to determine the consequences of the inoculum effect on bacterial population dynamics under treatment with antimicrobials.

Methods

We used the mathematical multi-hit model to quantify the effect of the inoculum on the pharmacodynamic parameters. The model describes antimicrobial action mechanistically, which allowed us to test various hypotheses concerning the mechanistic basis of the inoculum effect.

Results

Our model showed that the inoculum effect can arise from the binding dynamics of antimicrobial molecules to bacterial targets alone and does not require enzymatic degradation of antimicrobials. With enzymatic degradation, however, the inoculum effect is more pronounced. We propose to include the inoculum effect when measuring antimicrobial efficacy, i. e. to extend the pharmacodynamic function with the inoculum effect. This extended pharmacodynamic function mimiced simple long-term population dynamics well. More complex scenarios were only captured with the mechanism-based multi-hit model. In simulations with competing antimicrobial-sensitive and -resistant bacteria, neglecting the inoculum effect lead to an overestimation of the competitive ability of the resistant strain.

Conclusions

Our work emphasizes that the pharmacodynamic function — and in general any efficacy measure, e.g. the MIC — should include information about the inoculum size on which it is based, and ideally account for the inoculum effect.
CompScore: boosting structure-based virtual screening performance by incorporating docking scoring functions components into consensus scoring
Authors: Perez-Castillo Yunierkis , Sotomayor-Burneo Stellamaris , Jimenes-Vargas Karina , Gonzalez-Rodriguez Mario , Cruz-Monteagudo Maykel , Armijos-Jaramillo Vinicio , Cordeiro M. Natália D. S. , Borges Fernanda , Sánchez-Rodríguez Aminael , Tejera Eduardo
Published: February 2019

Consensus scoring has become a commonly used strategy within structure-based virtual screening (VS) workflows with improved performance compared to those based in a single scoring function. However, no research has been devoted to analyze the worth of docking scoring functions components in consensus scoring. We implemented and tested a method that incorporates docking scoring functions components into the setting of high performance VS workflows. This method uses genetic algorithms for finding the combination of scoring components that maximizes the VS enrichment for any target. Our methodology was validated using a dataset that contains ligands and decoys for 102 targets that has been widely used in VS validation studies. Results show that our approach outperforms other methods for all targets. It also boosts the initial enrichment performance of the traditional use of whole scoring functions in consensus scoring by an average of 45%. CompScore is freely available at: http://bioquimio.udla.edu.ec/compscore/
Retrieval Practice Facilitates Judgments of Learning Through Multiple Mechanisms
Authors: Chen Xi , Zhang Mengting , Liu Xiaonan L.
Published: February 2019

Prior studies have shown that predictions of subsequent performance (i.e., Judgments of Learning, JoLs) following practice tests are more accurate than those following re-study. The majority of studies have suggested that retrieval practice allows people to base their predictions on the current retrieval outcomes so that they assign a higher likelihood of remembering the answers with high confidence. We speculated that other information made available through retrieval practice might also be important for JoLs. In the present study, we asked participants to study word pairs and undergo either a practice test or re-study. Two testing formats (cued-recall and multiple choice) were administrated for practice tests in two separate experiments. After each practice trial, participants rated their confidence in the current retrieval accuracy (test) or confidence in acquisition (re-study), followed by a JoL rating where participants predicted their performance in the final test one day later. The results of both experiments showed that the correlation between JoL ratings and the final accuracy was higher for trials practiced with testing. Moreover, using mediation analyses, we found that this high correspondence was only partially mediated by participants’ confidence in practice tests. More importantly, the reaction time of retrieval also significantly mediated the correspondence between JoLs and the final accuracy, suggesting that participants were able to correctly base their JoLs on multiple sources of information that is made available through retrieval practice. We conclude that practice testing benefits JoLs through multiple mechanisms.
Strategies for understanding dynamic, personalized profiles of host-derived proteins and microbes from human stool
Authors: Casavant Ellen , Dethlefsen Les , Sankaran Kris , Sprockett Daniel , Holmes Susan , Relman David A. , Elias Joshua E.
Published: February 2019

Measuring host proteins through noninvasive stool-based assays opens new avenues for characterizing states of gastrointestinal health. However, the extent to which these proteins vary over time and between healthy subjects is poorly characterized. Here, we characterize technical and biological sources of variability in mass spectrometry-based measurements of host proteins in stool. We identify the proteins that most vary over time within an individual, and among different individuals. Finally, we examine and compare temporal and inter-individual variation in host protein and bacterial taxonomic profiles of the same fecal specimens. To address these issues, five self-reported healthy individuals were each sampled eight times over four weeks. First, we demonstrate that mass spectrometry-based identification and label-free quantification of stool proteins exhibit non-significant variability (p>0.05) between both technical and preparative replicates for a subset of 78 proteins, supporting the utility of this method for biomarker measurement. Second, although 13 human stool proteins varied significantly in relative abundance over time within individuals, 58 proteins varied significantly (at least four-fold) between subjects. The average pair-wise difference between individuals was greater than the average within-subject difference for both the proteome and microbiome datasets (p<0.0001). Fecal host proteins, like the traditional fecal protein marker, calprotectin, unambiguously pointed to innate and adaptive immune responses. For example, one subject’s fecal protein profile suggested a sub-clinical inflammatory state. From these data, we conclude that host-centric protein measurements in stool reveal a wide range of variation during states of apparent health, and add a valuable complementary insight into host-microbiota relationships.

IMPORTANCE

Human proteins in stool hold untapped potential for characterizing gastrointestinal health. To fully harness this potential and create a baseline of healthy stool protein abundances and identifications, it will be important to establish the extent to which these proteins might vary in the absence of disease. This study quantifies the major sources of variation in stool protein abundance data. We assessed technical, preparative, temporal, and inter-subject variability of human protein abundances in stool and found that among these sources, differences between subjects accounted for the greatest amount of variation, followed by temporal differences, and then technical factors. Our paired microbiome analysis found matching patterns of temporal and inter-subject variability. By characterizing multiple variance parameters in host stool protein abundances, our analysis helps to contextualize a wide range of future disease-focused stool studies as well as elucidate host-microbe interactions.
Epilepsy in children in Papua New Guinea: a longitudinal cohort study
Authors: Mond Casparia , Vince John D , Duke Trevor
Published: February 2019

Background

Epilepsy affects up to 1-4% of children living in low income and middle countries, however there are few studies of the problems faced by children with epilepsy in such settings.

Aim

To document the characteristics and situation for children with epilepsy in Port Moresby, an urban area in Papua New Guinea, a low-middle income country in the Western Pacific region. To describe the types of epilepsy, associated comorbidities, treatment access and barriers, the adequacy of seizure control, the quality of life and developmental opportunities, and the difficulties faced by children with epilepsy and their families.

Methods

A longitudinal cohort study, following children with epilepsy over 18-24 months. Mixed methods evaluations included assessments of seizure control, medications, neurodevelopment, and structured interviews with children and parents, and a parent-diary to record additional information.

Results

Forty-seven children with epilepsy were followed for a median of 18 months; 75% were being treated with phenobarbitone. Seizure control improved over time for some children, but inconsistent supply of phenobarbitone hindered better control. Twenty six (55%) children had some developmental delay. Children gave vivid descriptions of their experience of seizures. Most children and parents had a positive view of the future but faced many challenges including financial difficulties, fear of seizures especially at school, restriction of activity and stigma and discrimination.

Conclusion

Comprehensive care for children with epilepsy requires a good knowledge of the individual patient - including their seizure type and comorbidities, their family, and their strengths and vulnerabilities. It requires long term follow up, with a dedicated team of health professionals to provide support.
The use of mixture-density networks in the emulation of complex epidemiological individual-based models
Authors: Davis Christopher N , Hollingsworth T Deirdre , Caudron Quentin , Irvine Michael A
Published: February 2019

Complex, highly computational, individual-based models are abundant in epidemiology. For epidemics such as macro-parasitic diseases, detailed modelling of human behaviour and pathogen life-cycle are required in order to produce accurate results. This can often lead to models that are computationally-expensive to analyse and perform model fitting, and often require many simulation runs in order to build up sufficient statistics. Emulation can provide a more computationally-efficient output of the individual-based model, by approximating it using a statistical model. Previous work has used Gaussian processes in order to achieve this, but these can not deal with multi-modal, heavy-tailed, or discrete distributions. Here, we introduce the concept of a mixture density network (MDN) in its application in the emulation of epidemiological models. MDNs incorporate both a mixture model and a neural network to provide a flexible tool for emulating a variety of models and outputs. We develop an MDN emulation methodology and demonstrate its use on a number of simple models incorporating both normal, gamma and beta distribution outputs. We then explore its use on the stochastic SIR model to predict the final size distribution and infection dynamics. MDNs have the potential to faithfully reproduce multiple outputs of an individual-based model and allow for rapid analysis from a range of users. As such, an open-access library of the method has been released alongside this manuscript.

Author summary

Infectious disease modellers have a growing need to expose their models to a variety of stakeholders in interactive, engaging ways that allow them to explore different scenarios. This approach can come with a considerable computational cost that motivates providing a simpler representation of the complex model. We propose the use of mixture density networks as a solution to this problem. These are highly flexible, deep neural network-based models that can emulate a variety of data, including counts and over-dispersion. We explore their use firstly through emulating a negative-binomial distribution, which arises in many places in ecology and parasite epidemiology. We then explore the approach using a stochastic SIR model. We also provide an accompanying Python library with code for all examples given in the manuscript. We believe that the use of emulation will provide a method to package an infectious disease model such that it can be disseminated to the widest audience possible.
MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation
Authors: Tournier J-Donald , Smith Robert , Raffelt David , Tabbara Rami , Dhollander Thijs , Pietsch Maximilian , Christiaens Daan , Jeurissen Ben , Yeh Chun-Hung , Connelly Alan
Published: February 2019

MRtrix3 is an open-source, cross-platform software package for medical image processing, analysis and visualization, with a particular emphasis on the investigation of the brain using diffusion MRI. It is implemented using a fast, modular and flexible general-purpose code framework for image data access and manipulation, enabling efficient development of new applications, whilst retaining high computational performance and a consistent command-line interface between applications. In this article, we provide a high-level overview of the features of the MRtrix3 framework and general-purpose image processing applications provided with the software.
Large-scale brain network dynamics provide a measure of psychosis and anxiety in 22q11.2 deletion syndrome
Authors: Zöller Daniela , Sandini Corrado , Karahanoğlu Fikret Işik , Padula Maria Carmela , Schaer Marie , Eliez Stephan , Van De Ville Dimitri
Published: February 2019

Prodromal positive psychotic symptoms and anxiety are two strong risk factors for schizophrenia in 22q11.2 deletion syndrome (22q11DS). The analysis of large-scale brain network dynamics during rest is promising to investigate aberrant brain function and identify potentially more reliable biomarkers. We retrieved and examined dynamics of large-scale functional brain networks using innovation-driven co-activation patterns (iCAPs) and probed into functional signatures of prodromal psychotic symptoms and anxiety. Patients with 22q11DS had shorter activation in cognitive brain networks and longer activation in emotion processing networks. Functional signatures of prodromal psychotic symptoms confirmed an implication of cingulo-prefrontal salience network activation duration and coupling. Functional signatures of anxiety un-covered an implication of amygdala activation and coupling, indicating differential roles of dorsal and ventral sub-divisions of anterior cingulate and medial prefrontal cortices. These results confirm that the dynamic nature of brain network activation contains essential function to develop clinically relevant imaging markers of psychosis vulnerability.
Ion Condensation onto Ribozyme is Site-Specific and Fold-Dependent
Authors: Hori Naoto , Denesyuk Natalia A. , Thirumalai D.
Published: February 2019

The highly charged RNA molecules, with each phosphate carrying a single negative charge, cannot fold into well-defined architectures with tertiary interactions, in the absence of ions. For ribozymes, divalent cations are known to be more efficient than monovalent ions in driving them to a compact state although often Mg2+ ions are needed for catalytic activity. Therefore, how ions interact with RNA is relevant in understanding RNA folding. It is often thought that the most of the ions are territorially and non-specifically bound to the RNA, as predicted by the counterion condensation (CIC) theory. Here, we show using simulations of Azoarcus ribozyme, based on an accurate coarse-grained Three Site Interaction (TIS) model, with explicit divalent and monovalent cations, that ion condensation is highly specific and depends on the nucleotide position. The regions with high coordination between the phosphate groups and the divalent cations are discernible at very low concentrations when the ribozyme does not form tertiary interactions. Surprisingly, these regions also contain the secondary structural elements that nucleate subsequently in the self-assembly of RNA, implying that ion condensation is determined by the architecture of the folded state. These results are in sharp contrast to interactions of ions (monovalent and divalent) with rigid charged rods in which ion condensation is uniform and position independent. The differences are explained in terms of the dramatic non-monotonic shape fluctuations in the ribozyme as it folds with increasing Mg2+ or Ca2+ concentration.