bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Gestational Diabetes Mellitus With Neonatal Respiratory Morbidity
Authors: Werner Erika F. , Romano Megan E. , Rouse Dwight J. , Sandoval Grecio , Gyamfi-Bannerman Cynthia , Blackwell Sean C. , Tita Alan T.N. , Reddy Uma M. , Jain Lucky , Saade George R. , Iams Jay D. , Clark Erin A.S. , Thorp John M. , Chien Edward K. , Peaceman Alan M. , Swamy Geeta K. , Norton Mary E. , Casey Brian M. , Caritis Steve N. , Tolosa Jorge E. , Sorokin Yoram ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU)*
Published: January 2019

OBJECTIVE:

To assess neonatal respiratory morbidity in pregnancies with and without gestational diabetes mellitus (GDM) at imminent risk of late preterm delivery in a modern U.S. cohort.

METHODS:

Secondary analysis of a randomized placebo-controlled trial in which women with singleton pregnancies at high risk for delivery between 34 0/7 and 36 5/7 weeks of gestation were allocated to betamethasone or placebo. The primary outcome for the trial and this secondary analysis was a composite outcome of neonatal respiratory morbidity in the first 72 hours of life. Secondary outcomes included neonatal severe respiratory complications, neonatal intensive care unit (NICU) admission greater than or equal to 3 days, and hyperbilirubinemia. We examined associations between neonatal morbidities and GDM status after adjustment for baseline differences and study group allocation using modified Poisson regression. Models incorporating a product interaction term between GDM status and treatment arm (betamethasone or placebo) were also evaluated.

RESULTS:

Of the 2,831 women enrolled in the trial, 306 (10.8%) had GDM. Women with GDM were significantly older and were more likely to be parous and to have hypertensive disorders of pregnancy than those without GDM, but they were similar regarding race, gestational age at randomization (35.6 weeks) and at delivery (36.1 weeks), and study group assignment. Neonates born to women with GDM were no more likely to meet the primary outcome than those born to women without GDM, even after adjusting for differences in age, parity, and hypertensive disorders of pregnancy (12.1% vs 13.1%, adjusted RR 0.84; 95% CI 0.61–1.17), nor were they more likely to have severe respiratory complications or prolonged NICU admission.

CONCLUSION:

Maternal GDM is not associated with increased neonatal respiratory morbidity in this study population who were at high risk for late preterm birth.
Postoperative Opioid Consumption After Scheduled Compared With Unscheduled Cesarean Delivery
Authors: Prabhu Malavika , Dolisca Sarah , Wood Rachel , James Kaitlyn , Bateman Brian T. , Barth William H. , Wylie Blair J.
Published: January 2019

OBJECTIVE:

To identify characteristics associated with high inpatient daily opioid consumption after cesarean delivery.

METHODS:

This is a retrospective cohort study of all cesarean deliveries performed under neuraxial anesthesia with neuraxial morphine, at a single institution from January 1, 2015, to December 31, 2015. Women with preoperative opioid use disorder or chronic opioid use were excluded. Sociodemographic data, medical comorbidities, use of anxiolytics or antidepressants, smoking history, nonopioid substance use, intrapartum and cesarean delivery characteristics, and opioid consumption data (converted to morphine milligram equivalents) were abstracted. We defined high opioid use as a mean daily opioid consumption, standardized to the postoperative length of stay (excluding the first 24 postoperative hours to account for neuraxial morphine), greater than the 75th percentile of all opioid consumption. We used multivariable Poisson regression, stratified by whether or not cesarean delivery was scheduled, to identify characteristics associated with high opioid consumption.

RESULTS:

Among 949 women who underwent cesarean delivery, the mean (SD) and median (interquartile range) daily opioid consumption was 48.6 (22.8) and 44.6 (36.6–66.6) morphine milligram equivalents, respectively. Among those women with high opioid consumption, the mean (SD) and median (interquartile range) daily opioid consumption was 78.8 (8.5) and 78.3 (72.9–83.5) morphine milligram equivalents, respectively. Daily opioid consumption among those with high consumption was similar among women with scheduled compared with unscheduled cesarean delivery. Sociodemographic characteristics were similar among women with and without high opioid consumption. No sociodemographic, antepartum, or intrapartum characteristics were associated with high opioid consumption for either women having unscheduled or scheduled cesarean deliveries.

CONCLUSION:

For a quarter of women undergoing cesarean delivery, daily consumption of opioids is equivalent to 10 tablets of oxycodone 5 mg daily. No characteristics were associated with high opioid use for women having a scheduled or unscheduled cesarean delivery. Understanding opioid consumption after cesarean delivery is critical to managing women's postoperative pain while decreasing opioid exposure and risks of long-term opioid use disorder.
A Parent-Targeted and Mediated Video Intervention to Improve Uptake of Pain Treatment for Infants During Newborn Screening
Authors: Lavin Venegas Carolina , Taljaard Monica , Reszel Jessica , Dunn Sandra , Graham Ian D. , Harrold JoAnn , Larocque Catherine , Nicholls Becky , Nicholls Stuart , O'Flaherty Pat , Squires Janet , Stevens Bonnie , Trépanier Marie-Josée , Harrison Denise
Published: January 2019

Most newborns undergo newborn screening blood tests. Breastfeeding, skin-to-skin care, and sweet solutions effectively reduce pain; however, these strategies are inconsistently used. We conducted a 2-armed pilot randomized controlled trial in a mother-baby unit to examine the feasibility and acceptability of a parent-targeted and -mediated video demonstrating use of these pain-reducing strategies and to obtain preliminary effectiveness data on uptake of pain management. One hundred parent-newborn dyads were randomized to view the video or receive usual care (51 intervention and 49 control arm). Consent and attrition rates were 70% and 1%, respectively. All participants in the intervention arm received the intervention as planned and reported an intention to recommend the video and to use at least 1 pain treatment with breastfeeding or skin-to-skin care preferred over sucrose. In the intervention arm, 60% of newborns received at least 1 pain treatment compared with 67% in the control arm (absolute difference, −7%; 95% confidence interval, −26 to 12). The video was well accepted and feasible to show to parents. As there was no evidence of effect on the use of pain management, major modifications are required before launching a full-scale trial. Effective means to translate evidence-based pain knowledge is warranted.
Scrambler therapy: what's new after 15 years? The results from 219 patients treated for chronic pain
Authors: Ricci Marianna , Fabbri Laura , Pirotti Sara , Ruffilli Nicola , Foca Flavia , Maltoni Marco
Published: January 2019

Chronic pain is often difficult to treat, requiring a comprehensive multidisciplinary therapeutic intervention and a high level of management expertise.

This is particularly true for patients who are unresponsive to standard treatments for chronic pain, for which Scrambler Therapy (ST) is indicated. The aim of the present study was to evaluate the impact of ST on patient-reported moderate to severe chronic pain.

This was a prospective trial on 219 patients affected by chronic pain from April 2010 to March 2016. The study consisted of 2 consecutive weeks of treatment with ST (one 30-min daily session, 5 days a week) (T0, T1, T2) and a 2-week follow-up (T3, T4). Patients were asked to describe the pain using the Numeric Rating Scale (NRS) immediately prior to and after the treatment.

Two hundred nineteen patients were treated for chronic pain of different nature with mean values of 6.44 (± 2.11) at T0, 3.22 (± 2.20) at T2, and 3.19 (± 2.34) at T4. A reduction in the symptomatology from T0 to T2 was maintained throughout T4 (P value < .0001). Of the 219 patients treated with ST, 83 (37.9%) had cancer pain and 136 (62.1%) had non-cancer pain. No adverse events were reported.

Future research should focus on individual response, retreatment, and maintenance therapy. The data showed a statistically significant impact of ST, which was maintained during follow-up, on patients suffering from chronic pain of different nature.
The impact of SimMan on resident training in emergency skills
Authors: Liu Yu , Zhang Yanshu , Zhang Lei , Bai Hongliang , Wang Gang , Guo Litao
Published: January 2019

The purpose of this study was to analyze the role of SimMan in resident training of emergency skills.

Forty-five 1st year medical residents were selected for this study. All participants were divided into groups and each participant performed different roles during training. Clinical cases were selected using the tutor mode/auto mode in the SimMan computer system in order to train and assess each group. A pre-test was administered to the 45 residents before emergency medical technician (EMT) skill training. Finally, a post-test was conducted with SimMan after training. Tutors scored the student's performance and recorded the overall time for the procedure.

Before training, the overall qualification rate was 44.44%. The average score of the 9 groups was 62.78 ± 8.84 and the average 1st aid duration was 519.22 ± 34.35 seconds. After the training, the overall qualification rate was 100%. The average score of the 9 groups was 80.89 ± 7.39. The average 1st aid duration was 453.56 ± 24.40 seconds. The P values in comparing pre- and post-training data were .009, <.001 and <.001.

An integrated learning approach using SimMan as a tool for training and examination can help training residents develop emergency skills, teamwork, and communication.
Grip strength can be used to evaluate postoperative residual neuromuscular block recovery in patients undergoing general anesthesia
Authors: Pei Da-Qing , Zhou Hong-Mei , Zhou Qing-He
Published: January 2019

Background:

Residual postoperative neuromuscular blockade is an important clinical issue. Neuromuscular monitoring is usually used to evaluate neuromuscular recovery in patients undergoing general anesthesia. However, this procedure is inconvenient and not widely adopted. We aimed to examine the correlation between grip strength and train-of-four ratio (TOFr) to examine whether assessing grip strength can be used clinically to monitor residual neuromuscular blockade.

Methods:

One hundred twenty patients with ASA I or II scheduled for laparoscopic cholecystectomy under general anesthesia were enrolled in this study. All patients were randomly selected to receive standard anesthesia induction with either 0.6 mg·kg−1 rocuronium or 0.2 mg·kg−1 cisatracurium. Grip strength was tested in all patients using an electronic device before anesthesia and when TOFr values of 0.7, 0.8, and 0.9, and an hour later of TOFr value of 0.25. The time required for a change in TOFr values from 0.25 to 0.75 and 0.9 was evaluated. Spearman rank correlation analysis was performed to determine correlations between grip strength and TOFr.

Results:

Spearman rank correlation analysis indicated that there was a significant correlation between grip strength and TOFr during patient recovery from general anesthesia (correlation coefficient for grip strength recovery [r
s] = 0.886). Subgroup analysis revealed that there were no differences in mean maximum grip value recovery between patients treated with rocuronium and those treated with cisatracurium when TOFr was 0.7, 0.8, and 0.9 or when the TOFr was 0.25 after 60 minutes (all P 
>.05). Recovery of TOFr from 0.25 to 0.75 and from 0.25 to 0.9 was longer in patients treated with rocuronium than in those treated with cisatracurium (both P <.001).

Conclusion:

There was a strong correlation between grip strength and TOFr during recovery from general anesthesia. Evaluation of grip strength can be used as an additional strategy to evaluate postoperative residual neuromuscular blockade.
Predictive models composed by radiomic features extracted from multi-detector computed tomography images for predicting low- and high- grade clear cell renal cell carcinoma
Authors: He Xiaopeng , Zhang Hanmei , Zhang Tong , Han Fugang , Song Bin
Published: January 2019

To evaluate the values of conventional image features (CIFs) and radiomic features (RFs) extracted from multi-detector computed tomography (MDCT) images for predicting low- and high-grade clear cell renal cell carcinoma (ccRCC).

Two hundred twenty-seven patients with ccRCC were retrospectively recruited. Five hundred seventy features including 14 CIFs and 556 RFs were extracted from MDCT images of each ccRCC. The CIFs were extracted manually and RFs by the free software—MaZda. Least absolute shrinkage and selection operator (Lasso) was applied to shrink the high-dimensional data set and select the features. Five predictive models for predicting low- and high-grade ccRCC were constructed by the selected CIFs and RFs. The 5 models were as follows: model of minimum mean squared error (minMSE) of CIFs (CIF-minMSE), minMSE of cortico-medullary phase (CMP) of kidney (CMP-minMSE), minMSE of parenchyma phase (PP) of kidney (PP-minMSE), the combined model of CIF-minMSE and CMP-minMSE (CIF-CMP-minMSE), and the combined model of CIF-minMSE and PP-minMSE (CIF-PP-minMSE). The Lasso regression equation of each model was constructed, and the predictive values were calculated. The receiver operating characteristic (ROC) curves of predictive values of the 5 models were drawn by SPSS19.0, and the areas under the curves (AUCs) were calculated.

According to Lasso regression, 12, 19 and 10 features were respectively selected from the CIFs, RFs of CMP image and that of PP images to construct the 5 predictive models. The models ordered by their AUCs from large to small were CIF-CMP-minMSE (AUC: 0.986), CIF-PP-minMSE (AUC: 0.981), CIF-minMSE (AUC: 0.980), CMP-minMSE (AUC: 0.975), and PP-minMSE (AUC: 0.963). The maximum diameter of the largest axial section of ccRCC had a maximum weight in predicting the grade of ccRCC among all the features, and its cutoff value was 6.15 cm with a sensitivity of 0.901, a specificity of 0.963, and an AUC of 0.975.

When combined with CIFs, RFs extracted from MDCT images contributed to the larger AUC of the predictive model, but were less valuable than CIFs when used alone. The CIF-CMP-minMSE was the optimal predictive model. The maximum diameter of the largest axial section of ccRCC had the largest weight in all features.
Efficacy of perampanel for anti-N-methyl-D-aspartate receptor encephalitis
Authors: Akiyama Hisanao , Sasaki Rie , Hasegawa Yasuhiro
Published: January 2019

Rationale:

We report this 1st case because perampanel may be effective against the seizures and abnormal behavior that occur in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.

Patient concerns:

The patient was a healthy 26-year-old woman who suddenly developed seizures and exhibited abnormal behavior.

Diagnoses:

NMDAR encephalitis was diagnosed based on positive NMDAR antibody on cerebrospinal fluid analysis.

Interventions:

Treatment with anticonvulsants and sedatives was started immediately, along with steroid pulse therapy and plasmapheresis, but these measures did not adequately control the repeated seizures and abnormal behavior. However, with the addition of oral perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, the seizures and abnormal behavior promptly disappeared.

Outcomes:

The patient was transferred to the rehabilitation hospital and returned to her job.

Lessons:

It appears that perampanel rapidly eliminated these clinical features by inhibiting inflow of abnormal glutamic acid and attenuating nerve hyperexcitability by acting as a selective and noncompetitive antagonist of AMPA receptors that had increased in the postsynaptic membrane due to anti-NMDAR encephalitis. To the best of our knowledge, there are no other reports showing that perampanel was effective against anti-NMDAR encephalitis. This case suggests that perampanel may be effective against the seizures and abnormal behavior that occur in anti-NMDAR encephalitis.
Exercise training as an adjunctive therapy to montelukast in children with mild asthma
Authors: Zhang Yan-Feng , Yang Lin-Dong
Published: January 2019

Background:

This study investigated the effectiveness and safety of exercise training (ET) as an adjunctive therapy to montelukast for children with mild asthma (MA).

Methods:

A total of 72 children, ages 4 to 12 years with MA were randomly assigned to a treatment group or a control group at a ratio of 1:1. The subjects in the treatment group received ET plus montelukast, while the participants in the control group received montelukast alone. The primary endpoint was lung function, as measured by forced expiratory volume in 1 second (FEV1) and ratio between FEV1 and forced vital capacity (FEV1/FVC). The secondary endpoints included the symptom improvements, as measured by clinical assessment score, and quality of life (QoL), as assessed with Paediatric Allergic Disease Quality of Life Questionnaire (PADQLQ) scores. In addition, adverse events were also assessed during the period of this study. All outcomes were measured at baseline, at the end of 6-week treatment and 2-week follow-up after the treatment.

Results:

After 6-week treatment and 2-week follow-up, although ET plus montelukast did not show better effectiveness in improving lung function, as evaluated by the FEV1 (P > .05) and FEV1/FVC (P > .05) than montelukast alone, significant relief in clinical symptoms (P < .01), and improvement in QoL (P < .01) have achieved. Additionally, both groups had similar safety profile.

Conclusion:

The results of this study showed that ET as an adjunctive therapy to montelukast may benefit for children with MA. Further studies are still needed to warrant the results of this study.
Top 100 cited articles on infection in orthopaedics
Authors: Jiang Yu , Hu Renjing , Zhu Guoxing
Published: January 2019

Purpose:

The infection is an essential problem in the clinical practice in orthopedics. The bibliometric analysis was conducted to evaluate the top 100 cited articles on infection in orthopaedics.

Methods:

The Web of Science (WoS) Core Database was comprehensively searched from 1975 to 2017, and the literature search was limited in Science Citation Index Expanded (SCI-E). The subject terms included “infection”, “infectious”, and “infect∗”. All retrieved articles were filtrated by selecting the subspecialty of “Orthopedics”. The searching results were listed by citation times to identify the top 100 cited articles. Significant information was elicited, including the authors, journals, countries, institutions, published year, and types of publication.

Results:

A significant increase was observed in the number of annual publications focusing on infection in orthopedics worldwide. Each of the top 100 cited articles was cited more than 150 times. Total citation times was positively associated with citation times in 2016 (P <.01) and mean citation times per year (P <.01). Conversely, age of the article was negatively associated with citation times in 2016 (P <.01) and mean citation times per year (P <.01). Besides, citation times in 2016 was positively related to mean citation times per year (P <.01). The United States was the most productive country, surgery was the most popular subspecialty and Journal of Bone and Joint Surgery American Volume was the most popular journal.

Conclusion:

Infection in orthopaedics has attracted more and more researchers’ concern. As for the top 100 cited articles, there were significant relationships among total citation times, citation times in 2016 and mean citation times per year as well as age of the article. The United States was the most productive country, surgery was the most popular subspecialty and Journal of Bone and Joint Surgery American Volume was the most popular journal.
A survey on the perception and attitude change of first-line healthcare providers after child abuse education in South Korea
Authors: Paek So Hyun , Kwak Young Ho , Noh Hyun , Jung Jin Hee
Published: January 2019

We had designed an educational program for early reporting of suspected child abuse for healthcare providers in South Korea. The purpose of study was to evaluate the effectiveness of education program for health care providers as pilot study. The educational program consisted of two 2-hour-long didactic lectures and was held at 15 hospitals between July and December 2016. We conducted a survey study with physicians, nurses, emergency medical technicians, and other hospital staff. Participants completed survey questionnaires before and after the lecture and 3 months later. The questionnaire contained 3 sections: practical knowledge regarding child abuse, confidence in reporting, and willingness to report. A 10-point Likert scale was used to evaluate the responses. A total of 1103 participants working in 15 different hospitals attended the educational program. In all, 663 participants (75.5%) completed the survey with nurses at 61.7% and physicians at 22%. 26.4% had previously received education about child abuse and reporting methods, and 227 (34.2%) had experience with reporting (direct and indirect) child abuse. The score about knowledge improved from 5.28 points before to 8.03 after the educational program, and was 7.1 after 3 months (P < .001), using a 10-point Likert scale. The confidence increased from 4.76 before the program to 7.59 after it, and was 6.6 after 3 months (P < .001). The willingness to report increased from 7.46 before the program to 8.68 after it, and was 8.14 after 3 months (P < .001). Participants’ satisfaction with the education program was 8.3 points immediately after education and 7.6 points after 3 months. The recommendation index of curriculum was 8.4 points before program and 8.1 points after 3 months. The educational program on the assessment of child abuse and reporting methods increased healthcare professionals’ knowledge and confidence and improved their willingness to report suspected child abuse in a low-perception environment.
Deletion of Lats 1 and 2 in mouse pancreatic acinar cells induces pancreatic fibrosis and inflammation
Authors: Gao Ming , Liu Jun , Nipper Michael , Sharkey Francis E. , Johnson Randy L. , Crawford Howard C. , Chen Yidong , Wang Pei
Published: January 2019

Objective

The Hippo signaling pathway is known for regulating proliferation, differentiation, organ size, and tumorigenesis. Large tumor suppressor kinase 1 and 2 (LATS1&2) are the core kinases of this pathway, whose functions in both the normal pancreas and pancreatic diseases are unclear. We studied the function of LATS1&2 specifically in pancreatic acinar cells of adult mice.

Design

We generated mice with adult pancreatic acinar cell–specific deletion ofLats1&2genes by using CreER/LoxP. Pancreata were analyzed by histological examination, immunostaining, western blot, and RNA-sequencing.

Results

Deletion ofLats1&2genes in adult pancreatic acinar cells resulted in rapid development of pancreatic inflammation and fibrosis. Loss of Lats1&2 did not directly induce acinar cell proliferation or apoptosis, but resulted in pancreatic stellate cell (PSC) activation followed by immune cell infiltration and acinar-to-ductal metaplasia. These effects were mediated by the Hippo downstream effectors YAP1/TAZ. By using neutralizing antibody to block CTGF, a YAP1/TAZ target, the inflammation and fibrosis were reduced. Our RNA-sequencing data identified upregulation of fibroinflammatory genes inLats1&2null pancreata, which may play important roles in stimulating PSC activation and promoting pancreatic fibrosis, as well as inflammation.

Conclusions

Deletion of theLats1&2genes from adult acinar cells leads to the YAP1/TAZ dependent upregulation of a fibroinflammatory program. Our results emphasize the critical role of Lats1&2 in regulating PSC activation. Our findings identify new strategies for controlling pancreatic inflammation and fibrosis in diseases such as pancreatitis and pancreatic cancer.
Relevance of the iron-responsive element (IRE) pseudotriloop structure for IRP1/2 binding and validation of IRE-like structures using the yeast three-hybrid system
Authors: Chen Shih-Cheng , Olsthoorn René C.L.
Published: January 2019

Iron-responsive-elements (IREs) are ~35-nucleotide (nt) stem-loop RNA structures located in 5′ or 3′ untranslated regions (UTRs) of mRNAs, and mediate post-transcriptional regulation by their association with IRE-binding proteins (IRPs). IREs are characterized by their apical 6-nt loop motif 5′-CAGWGH-3′ (W = A or U and H= A, C or U), the so-called pseudotriloop, of which the loop nts C1 and G5 are paired, and the none-paired C between the two stem regions. In this study, the yeast three-hybrid (Y3H) system was used to investigate the relevance of the pseudotriloop structure of ferritin light chain (FTL) for the IRE-IRP interaction and the binding affinities between variant IRE(-like) structures and the two IRP isoforms, IRP1 and 2. Mutational analysis of FTL IRE showed that deletion of the bulged-out U6 of the pseudotriloop does not significantly affect its binding to either IRP1 or 2, but substitution with C enhances binding of both IRPs. In addition, IRP1 was found more sensitive toward changes in the pseudotriloop-stabilizing C1-G5 base pair than IRP2, while mutation of the conserved G3 was lowering the binding of both IRPs. In comparison to FTL IRE other variant IREs, IRE of 5′-aminolevulinate synthase 2 (ALAS2), SLC40A1 (also known as Ferroportin-1), and endothelial PAS domain protein 1 (EPAS1) mRNA showed slightly higher, similar, and slightly weaker affinity for IRPs, respectively, while SLC11A2 IRE exhibited very weak binding to IRP1 and medium binding to IRP2, indicating the different binding modes of IRP1 and 2. Notably, α-Synuclein IRE showed no detectable binding to either IRP1 or 2. Our results indicate that Y3H represents abona fidesystem to characterize binding between IRPs and various IRE-like structures.
Incorporating prior information into signal-detection analyses across biologically informed gene-sets
Authors: Zhang Mengqi , Gelfman Sahar , McCarthy Janice , Goldstein David B. , Allen Andrew S.
Published: January 2019

Signal detection analyses are used to assess whether there is any evidence of signal within a large collection of hypotheses. For example, we may wish to assess whether there is any evidence of association with disease among a set of biologically related genes. Such an analysis typically treats all genes within the sets similarly, even though there is substantial information concerning the likely importance of each gene within each set. For example, deleterious variants within genes that show evidence of purifying selection are more likely to substantially affect the phenotype than genes that are not under purifying selection, at least for traits that are themselves subject to purifying selection. Here we improve such analyses by incorporating prior information into a higher-criticism-based signal detection analysis. We show that when this prior information is predictive of whether a gene is associated with disease, our approach can lead to a significant increase in power. We illustrate our approach with a gene-set analysis of amyotrophic lateral sclerosis (ALS), which implicates a number of gene-sets containing SOD1 and NEK1 as well as showing enrichment of small p-values for gene-sets containing known ALS genes.
SHORT COMMUNICATION: Validation of a novel milk progesterone based tool to monitor luteolysis in dairy cows. Performance on cost-effective, on-farm measured data
Authors: Adriaens Ines , Saeys Wouter , Geerinckx Katleen , De Ketelaere Bart , Aernouts Ben
Published: January 2019

INTERPRETATIVE SUMMARY

Validation of luteolysis monitoring tool Adriaens.

Recently, a novel progesterone-based monitoring algorithm using synergistic control, PMASC, was developed. This algorithm employs the known luteal dynamics of the progesterone profile to estimate the moment of luteolysis with minimal dependence on the absolute measurement values. As its value and implementability strongly dependends on the number of samples it requires to obtain the desired accuracy, its performance on cost-effective, ‘smart’ sampled and on-farm measured data is demonstrated.

SHORT COMMUNICATION

Validation of a novel milk progesterone based tool to monitor luteolysis in dairy cows. Performance on cost-effective, on-farm measured data
Balancing sensitivity and specificity in distinguishing TCR groups by CDR sequence similarity
Authors: Thakkar Neerja , Bailey-Kellogg Chris
Published: January 2019

Repertoire sequencing is enabling deep explorations into the cellular immune response, including the characterization of commonalities and differences among T cell receptor (TCR) repertoires from different individuals, pathologies, and antigen specificities. In seeking to understand the generality of patterns observed in different groups of TCRs, it is necessary to balance how well each pattern represents the diversity among TCRs from one group (sensitivity) vs. how many TCRs from other groups it also represents (specificity). The variable complementarity determining regions (CDRs), particularly the third CDRs (CDR3s) interact with MHC-presented epitopes from putative antigens, and thus encode the determinants of recognition. We here systematically characterize the predictive power that can be obtained from CDR3 sequences, using representative, readily interpretable methods for evaluating CDR sequence similarity and then clustering and classifying sequences based on similarity. An initial analysis of CDR3s of known structure, clustered by structural similarity, helps calibrate the limits of sequence diversity among CDRs that might have a common mode of interaction with presented epitopes. Subsequent analyses demonstrate that this same range of sequence similarity strikes an appropriate specificity/sensitivity balance in distinguishing twins from non-twins based on overall CDR3 repertoires, classifying CDR3 repertoires by antigen specificity, and distinguishing general pathologies. We conclude that within this fairly broad range of sequence similarity, matching CDR3 sequences are likely to share specificities.
Large-scale proteomic analysis of human prefrontal cortex identifies proteins associated with cognitive trajectory in advanced age
Authors: Wingo Aliza P. , Dammer Eric B. , Breen Michael S. , Logsdon Benjamin A. , Duong Duc M. , Troncosco Juan C. , Thambisetty Madhav , Beach Thomas G. , Serrano Geidy E. , Reiman Eric M. , Caselli Richard J. , Lah James J. , Seyfried Nicholas T. , Levey Allan I. , Wingo Thomas S.
Published: January 2019

In advanced age, some individuals maintain a stable cognitive trajectory while others experience a rapid decline. Such variation in cognitive trajectory is only partially explained by traditional neurodegenerative pathologies. Hence, to identify new processes underlying variation in cognitive trajectory, we perform an unbiased proteome-wide association study of cognitive trajectory in a discovery (n=104) and replication cohort (n=39) of initially cognitively unimpaired, longitudinally assessed older-adult brain donors. We find 579 proteins associated with cognitive trajectory after meta-analysis. Notably, we present novel evidence for increased neuronal mitochondrial activities in cognitive stability regardless of the burden of traditional neuropathologies. Furthermore, we provide additional evidence for increased synaptic activities and decreased inflammation and apoptosis in cognitive stability. Importantly, we nominate proteins associated with cognitive trajectory, particularly the 38 proteins that act independently of neuropathologies and are also hub proteins of protein co-expression networks, as promising targets for future mechanistic studies of cognitive trajectory.
Comparing rates of introgression in parasitic feather lice with differing dispersal capabilities
Authors: Doña Jorge , Sweet Andrew D. , Johnson Kevin P.
Published: January 2019

Organisms vary in their dispersal abilities, and these differences can have important biological consequences, such as impacting the likelihood of hybridization events. However, there is still much to learn about the factors influencing hybridization, and specifically how dispersal ability affects the opportunities for hybridization. Here, using the ecological replicate system of dove wing and body lice (Insecta: Phthiraptera), we show that species with higher dispersal abilities exhibited increased genomic signatures of introgression. Specifically, we found a higher proportion of introgressed genomic reads and more reticulated phylogenetic networks in wing lice, the louse group with higher dispersal abilities. Our results are consistent with the hypothesis that differences in dispersal ability might drive the extent of introgression through hybridization.
Continent-wide structure of bacterial microbiomes of European Drosophila melanogaster suggests host-control
Authors: Wang Yun , Kapun Martin , Waidele Lena , Kuenzel Sven , Bergland Alan , Staubach Fabian
Published: January 2019

The relative importance of host-control, environmental effects, and stochasticity in the assemblage of host-associated microbiomes has been much debated. With recent sampling efforts, the underpinnings of D. melanogaster’s microbiome structure have become tractable on larger spatial scales. We analyzed the microbiome among fly populations that were sampled across Europe by the European Drosophila Population Genomics Consortium (DrosEU). We combined environmental data on climate and food-substrate, dense genomic data on host population structure, and microbiome profiling. Food-substrate, temperature, and host population-structure correlated with microbiome-structure. The microbes, whose abundance was co-structured with host populations, also differed in abundance between flies and their substrate in an independent survey, suggesting host-control. Patterns of enrichment and depletion of microbes between host and substrate were consistent with a model of host-control, where the host manipulates its microbiome for its benefit. Putative host-control was bacterial strain specific, supporting recent evidence for high specificity of D. melanogaster-microbe interaction.
Imaging the spontaneous flow of thought: Distinct periods of cognition contribute to dynamic functional connectivity during rest
Authors: Gonzalez-Castillo Javier , Caballero-Gaudes César , Topolski Natasha , Handwerker Daniel A. , Pereira Francisco , Bandettini Peter A.
Published: January 2019

Brain functional connectivity (FC) changes have been measured across seconds using fMRI. This is true for both rest and task scenarios. Moreover, it is well accepted that task engagement alters FC, and that dynamic estimates of FC during and before task events can help predict their nature and performance. Yet, when it comes to dynamic FC (dFC) during rest, there is no consensus about its origin or significance. Some argue that rest dFC reflects fluctuations in on-going cognition, or is a manifestation of intrinsic brain maintenance mechanisms, which could have predictive clinical value. Conversely, others have concluded that rest dFC is mostly the result of sampling variability, head motion or fluctuating sleep states. Here, we present novel analyses suggesting that rest dFC is influenced by short periods of distinct mental processing, and that the cognitive nature of such mental processes can be inferred blindly from the data. As such, several different behaviorally relevant whole-brain FC configurations may occur during a single rest scan even when subjects were continuously awake and displayed minimal motion. In addition, using low dimensional embeddings as visualization aids, we show how FC states—commonly used to summarize and interpret resting dFC—can accurately and robustly reveal periods of externally imposed tasks; however, they may be less effective in capturing periods of distinct cognition during rest.
Role of Disulfide Bonds and Topological Frustration in the Kinetic Partitioning of Lysozyme Folding Pathways
Authors: Muttathukattil Aswathy N. , Singh Prashant Chandra , Reddy Govardhan
Published: January 2019

Disulfide bonds in proteins can strongly influence the folding pathways by constraining the conformational space. Hen egg white lysozyme has four disulfide bonds and is widely studied for its antibacterial properties. Experiments on lysozyme infer that the protein folds through a fast and a slow pathway. However, the reasons for the kinetic partitioning in the folding pathways are not completely clear. Using a coarse-grained protein model and simulations, we show that two out of the four disulfide bonds, which are present in theα-domain of lysozyme, are responsible for the slow folding pathway. In this pathway, a kinetically trapped intermediate state, which is close to the native state is populated. In this state, the orientation ofα-helices present in theα-domain are misaligned relative to each other. The protein in this state has to partially unfold by breaking down the inter-helical contacts between the misaligned helices to fold to the native state. However, the topological constraints due to the two disulfide bonds present in theα-domain make the protein less flexible, and it is trapped in this conformation for hundreds of milliseconds. On disabling these disulfide bonds, we find that the kinetically trapped intermediate state and slow folding pathway disappear. Simulations mimicking the folding of protein without disulfide bonds in oxidative conditions show that the native disulfide bonds are formed as the protein folds indicating that folding guides the formation of disulfide bonds. The sequence of formation of the disulfide bonds is Cys64-Cys80 → Cys76-Cys94 → Cys30-Cys115 → Cys6-Cys127. Any disul-fide bond, which forms before its precursor in the sequence has to break and follow the sequence for the protein to fold. These results show that lysozyme also serves as a very good model system to probe the role of disulfide bonds and topological frustration in protein folding. The predictions from the simulations can be verified by single molecule fluorescence resonance energy transfer (FRET) or single molecule pulling experiments, which can probe heterogeneity in the folding pathways.
Computational Analysis Revealed Five Novel Mutations in HumanIL2RGgene Related to X-SCID
Authors: Mohammed Tamadur Babiker Abbas , Ali Asma Ali Hassan , Elemam Areeg ElsirAbdelgadir , Altayb Wala Omer Mohammed , Abbas Tebyan Ameer Abdelhameed , Hassan Mohamed Ahmed Salih
Published: January 2019

Background

X linked severe combined immunodeficiency (X-SCID) is a life-threatening disorder. It is due to mutation of the interleukin two receptor gamma-chain (IL2RG) gene. Nonsynonymous SNPs (nsSNPs) are the most common polymorphism, known to be deleterious or disease-causing variations because they alter protein sequence, structure, and function. Objective: is to reveal the effect of harmful SNPs in the function and structure of IL2RG protein.

Method

Data on IL2RG was investigated from dbSNP/NCBI database. Prediction of damaging effect was done using sift, polyphen, provean and SNAP2.more software were used for more analysis: phd-snp, and and go, Pmut, Imutant.modeling was done using chimera and project hope. Gene interaction was done by gene mania.3UTR prediction was done using polymiRTS software.

Result

The in-silico prediction identified 1479 SNPs within IL2RG gene out of which 253 were coding SNPs, 50 took place in the miRNA 3 UTR, 21 occurred in 5 UTR region and 921 occurred in intronic regions. a total of 12 missense nsSNPs were found to be damaging by both a sequence homology-based tool (SIFT) and a structural homology-based method (PolyPhen), Five of them were novel; rs1322436793(G305R), rs1064794027(C182Y), rs111033620(G114D), rs193922347 (Y105C) and rs1293196743(Y91C), Two SNPs(Rs144075871andrs191726889) out of 50 in the 3UTR region were predicted to disrupt miRNAs binding sites and affect the gene expression.

Conclusions

Computational analysis of SNPs has become a very valuable tool in order to discriminate neutral SNPs from damaging SNPs. This study revealed 5 novel nsSNPs in the IL2RG gene by using different software and 21 SNPs in 3UTR. These SNPs could be considered as important candidates in causing diseases related to IL2RG mutation and could be used as diagnostic markers.
A simple linearization method unveils hidden enzymatic assay interferences
Authors: Pinto Maria Filipa , Ripoll-Rozada Jorge , Ramos Helena , Watson Emma E. , Franck Charlotte , Payne Richard J. , Saraiva Lucília , José Barbosa Pereira Pedro , Pastore Annalisa , Rocha Fernando , Martins Pedro M.
Published: January 2019

Enzymes are among the most important drug targets in the pharmaceutical industry. The bioassays used to screen enzyme modulators can be affected by unaccounted interferences such as time-dependent inactivation and inhibition effects. Using procaspase-3, caspase-3, and α-thrombin as model enzymes, we show that some of these effects are not eliminated by merely ignoring the reaction phases that follow initial-rate measurements. We thus propose a linearization method (LM) for detecting spurious changes of enzymatic activity based on the representation of progress curves in modified coordinates. This method is highly sensitive to signal readout distortions, thereby allowing rigorous selection of valid kinetic data. The method allows the detection of assay interferences even when their occurrence is not suspected a priori. By knowing the assets and liabilities of the bioassay, enzymology results can be reported with enhanced reproducibility and accuracy. Critical analysis of full progress curves is expected to help discriminating experimental artifacts from true mechanisms of enzymatic inhibition.
Distinguishing the signatures of local environmental filtering and regional trait range limits in the study of trait-environment relationships
Authors: Denelle Pierre , Violle Cyrille , Munoz François
Published: January 2019

Understanding the imprint of environmental filtering on community assembly along environmental gradients is a key objective of trait-gradient analyses. Depending on local constraints, this filtering generally entails that species departing from an optimum trait value have lower abundances in the community. The Community-Weighted Mean (CWM) and Variance (CWV) of trait values are then expected to depict the optimum and intensity of filtering, respectively. However, the trait distribution within the regional species pool and its limits can also affect local CWM and CWV values apart from the effect of environmental filtering. The regional trait range limits are more likely to be reached in communities at the extremes of environmental gradients. Analogous to the mid-domain effect in biogeography, decreasing CWV values in extreme environments can then represent the influence of regional trait range limits rather than stronger filtering in the local environment. We name this effect the “Trait-Gradient Boundary Effect” (TGBE). First, we use a community assembly framework to build simulated communities along a gradient from a species pool and environmental filtering with either constant or varying intensity while accounting for immigration processes. We demonstrate the significant influence of TGBE, in parallel to environmental filtering, on CWM and CWV at the extremes of the environmental gradient. We provide a statistical tool based on Approximate Bayesian Computation to decipher the respective influence of local environmental filtering and regional trait range limits. Second, as a case study, we reanalyze the functional composition of alpine plant communities distributed along a gradient of snow cover duration. We show that leaf trait convergence found in communities at the extremes of the gradient reflect an influence of trait range limits rather than stronger environmental filtering. These findings challenge correlative trait-environment relationships and call for more explicitly identifying the mechanisms responsible of trait convergence/divergence along environmental gradients.
Preformed Chromatin Topology Assists Transcriptional Robustness ofShhduring Limb Development
Authors: Paliou Christina , Guckelberger Philine , Schöpflin Robert , Heinrich Verena , Esposito Andrea , Chiariello Andrea M. , Bianco Simona , Annunziatella Carlo , Helmuth Johannes , Haas Stefan , Jerković Ivana , Brieske Norbert , Wittler Lars , Timmermann Bernd , Nicodemi Mario , Vingron Martin , Mundlos Stefan , Andrey Guillaume
Published: January 2019

Long-range gene regulation involves physical proximity between enhancers and promoters to generate precise patterns of gene expression in space and time. However, in some cases proximity coincides with gene activation, whereas in others preformed topologies already exist before activation. In this study, we investigate the preformed configuration underlying the regulation of theShhgene by its unique limb enhancer, theZRS, in vivoduring mouse development. Abrogating the constitutive transcription covering theZRSregion led to a shift within theShh-ZRScontacts and a moderate reduction inShhtranscription. Deletion of the CTCF binding sites around theZRSresulted in a loss of theShh-ZRSpreformed interaction and a 50% decrease inShhexpression but no phenotype, suggesting an additional, CTCF-independent mechanism of promoter-enhancer communication. This residual activity, however, was diminished by combining the loss of CTCF binding with a hypomorphic ZRS allele resulting in severeShhloss-of-function and digit agenesis. Our results indicate that the preformed chromatin structure of theShhlocus is sustained by multiple components and acts to reinforce enhancer-promoter communication for robust transcription.
Temporal changes in species composition affect a ubiquitous species’ views of patch quality
Authors: Bledsoe Ellen K. , Ernest S. K. Morgan
Published: January 2019

Metacommunity theory, particularly the patch dynamics archetype, suggests that an organism’s perspective of patch quality can depend solely on the local competitive environment. Across landscapes, however, shifts in species composition often co-occur with shifts in habitat, making it difficult to disentangle the role of competitors and environment on assessments of patch quality. Using 26 years of rodent community time-series data, we show that perception of patch quality by a small, ubiquitous granivore (Chaetodipus penicillatus) shifted with both spatial and temporal changes in species composition. In the mid-1990s,C. baileyi, a novel competitor, colonized and the study site.C. penicillatuspatch preference shifted with increasing abundance ofC. baileyi, including corresponding changes in estimated survival, probability of movement between patches, and the arrival of new individuals in patches. Changes in energy use on patches due to the establishment ofC. baileyipoint to a potential mechanism for the differences in patch quality perceived byC. penicillatus. These results demonstrate that experimental time-series data can be used to examine how changes in species composition and, specifically, changes in the competitive landscape, can affect perception of patch quality and patch preference.