bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of resveratrol for the treatment in patients with ulcerative colitis
Authors: Chen Yan-hui , Xiang Yi
Published: November 2019

Background:

This study will aim to systematically explore the efficacy of resveratrol for the treatment of patients with ulcerative colitis (UC).

Methods:

We will search the electronic databases of MEDLINE, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure up to the September 1, 2019 for randomized controlled trials (RCTs) that report on UC who have undergone resveratrol compared with other interventions. All electronic databases will be searched without restrictions of language. Two authors will independently conduct study screen, data extraction, and risk of bias assessment. Any disagreements between 2 authors will be resolved with a third author by discussion or consultation if it is necessary. RevMan 5.3 software will be applied for statistical analysis.

Results:

Outcomes include clinical remission, improvement of clinical symptoms, maintenance of remission, relapse rate, endoscopic assessment, histological assessment, quality of life, and adverse events.

Conclusion:

This study will provide most recent evidence of resveratrol for the treatment of patients with UC.

PROSPERO registration number:

PROSPERO CRD42019150849.
Thyroid-stimulating hormone is associated with nonalcoholic steatohepatitis in patients with chronic hepatitis B
Authors: Liu Liang , Li Ping , Mi Yuqiang , Liu Yonggang , Liu Yiqi , Zhang Peng
Published: November 2019

The relationship of thyroid function parameters with nonalcoholic steatohepatitis (NASH) in patients with chronic hepatitis B (CHB) remains unknown. Hence, we assessed the impact of thyroid function parameters on NASH in patients with CHB.

Consecutive patients with CHB with concurrent nonalcoholic fatty liver disease (NAFLD) were recruited. Liver histology and baseline examinations were carried out in each patient. The associated risk factors for NASH were evaluated.

A total of 361 patients with CHB with biopsy-proven NAFLD were included. There was a significant difference in the serum thyroid-stimulating hormone (TSH) level between patients with NASH and non-NASH (3.24 ± 2.00 vs 2.05 ± 1.35 mIU/L,P < .01). Moreover, the NASH prevalence in patients with euthyroidism was significantly higher than in the subclinical hypothyroidism (SCH) patients (P < .001). In multivariate analyses, higher serum concentration of TSH was significantly correlated with NASH (odds ratio [OR]: 1.69, 95% confidence interval [CI]: 1.24–2.31;P = .001). In particular, patients suffering from SCH had a higher risk of having NASH (OR: 4.28, 95% CI: 1.18–15.53;P = .027).

Elevated serum TSH level was the independent predictive factor of incident NASH in patients with CHB. Whether the thyroid function parameters should be integrated into future diagnostic scores predicting advanced diseases requires further study.
Mediation analyses of socioeconomic factors determining racial differences in the treatment of diffuse large B-cell lymphoma in a cohort of older adults
Authors: Guadamuz Jenny S. , Ozenberger Katharine , Qato Dima M. , Ko Naomi Y. , Saffore Christopher D. , Adimadhyam Sruthi , Cha Ashley S. , Moran Kellyn M. , Sweiss Karen , Patel Pritesh R. , Chiu Brian C.-H. , Calip Gregory S.
Published: November 2019

Despite near universal health coverage under Medicare, racial disparities persist in the treatment of diffuse large B-cell lymphoma (DLBCL) among older patients in the United States. Studies evaluating DLBCL outcomes often treat socioeconomic status (SES) measures as confounders, potentially introducing biases when SES factors are mediators of disparities in cancer treatment.

To examine differences in DLBCL treatment, we performed causal mediation analyses of SES measures, including: metropolitan statistical area (MSA) of residence; census-tract poverty level; and private Medicare supplementation using the Surveillance, Epidemiology and End Results-Medicare linked database between 2001 and 2011. In this retrospective cohort study of DLBCL patients ages 66+ years, we conducted a series of multivariable logistic regression analyses estimating odds ratios (OR) and 95% confidence intervals (CI) relating chemo- and/or immuno-therapy treatment and each SES measure, comparing non-Hispanic (NH)-black, Hispanic/Latino, and Asian/Pacific Islander (API) to NH-white patients.

Compared to NH-white patients, racial/ethnic minority patients had lower odds of receiving chemo- and/or immuno-therapy treatment (NH-black: OR 0.84, 95% CI 0.65, 1.08; API: OR 0.80, 95% CI 0.64, 1.01; Hispanic/Latino: OR 0.78, 95% CI 0.64, 0.96) and higher odds of lacking private Medicare supplementation and residence within an urban MSA and poor census tracts. Adjustment for SES measures as confounders nullified observed racial differences. In causal mediation analyses, between 31% and 38% of race/ethnicity differences were mediated by having private Medicare supplementation.

Providing equitable access to Medicare supplementation may reduce disparities in receipt of chemo- and/or immuno-therapy treatment in older DLBCL patients.
Intestinal Behçet disease associated with myelodysplastic syndrome accompanying trisomy 8 successfully treated with abdominal surgery followed by hematopoietic stem cell transplantation
Authors: Asano Tomoyuki , Sato Shuzo , Furuya Makiko Yashiro , Takahashi Hiroshi , Shichishima-Nakamura Akiko , Ohkawara Hiroshi , Fujiwara Tatsuo , Gunji Naohiko , Hashimoto Choichiro , Momma Tomoyuki , Saito Motonobu , Nakano Hiroshi , Watanabe Guy , Temmoku Jumpei , Fujita Yuya , Matsuoka Naoki , Kobayashi Hiroko , Watanabe Hiroshi , Mouri Mariko , Mashiyama Fumi , Sakuma Hiroko , Ohira Hiromasa , Mori Masaaki , Ikezoe Takayuki , Migita Kiyoshi
Published: November 2019

Rationale:

Intestinal Behçet disease (BD) with myelodysplastic syndrome (MDS) is a rare condition that is resistant to various immunosuppressive therapies. Several cases in which hematopoietic stem cell transplantation (HSCT) was effective for intestinal BD with MDS accompanying trisomy 8 have been reported.

Patient concerns:

We report an 18-year-old female with a 7-year history of BD. Colonoscopy demonstrated a huge ulcer in the cecum. Chromosomal examination revealed a karyotype of trisomy 8 in 87% of cells. Bone marrow examination revealed dysplastic cells in multilineages.

Diagnoses:

A diagnosis of intestinal BD associated with MDS accompanying trisomy 8 was made.

Interventions:

The patient underwent ileocecal resection due to microperforations of ileocecal ulcers; she then underwent allogeneic peripheral blood stem cell transplantation (PBSCT) with her mother as a donor.

Outcomes:

After the PBSCT, the patient's symptoms due to BD (fever, oral aphthae, abdominal pain, and genital ulcers) completely disappeared, with no severe adverse events.

Lessons:

The present case demonstrates that HSCT including PBSCT might be an effective new therapeutic option for refractory intestinal BD with MDS when immunosuppressive therapy has achieved insufficient efficacy.
Successful resection of giant abdominal hemophilic pseudotumor
Authors: Liu Shuzhong , Zhou Xi , Song An , Huo Zhen , Wang Yipeng , Liu Yong
Published: November 2019

Giant abdominal hemophilic pseudotumor is exceedingly rare, thus may bring great challenges to the timely and proper diagnosis and treatment of clinicians. The only definitive management is complete removal of the abdominal hemophilic pseudotumor. The objective of this article is to report surgical treatment and follow-up outcomes of three unusual cases with giant abdominal hemophilic pseudotumor.

We describe 3 patients with giant hemophilic pseudotumor involving the abdomen who were successfully treated with tumor resection. On presentation to our institution, the patients all had signs of giant cystic lesions in abdomen, and the patients’ most outstanding complaints were aggravated abdominal pain. All of three patients underwent complete excision of abdominal hemophilic pseudotumor. The patients showed adequate pain relief compared with the previous status.

Surgical resection is the most effective treatment option for patients with giant abdominal hemophilic pseudotumor who can undergo appropriate surgical treatment. This represents a safe and reasonable approach to sustainably relieve pain and other symptoms with giant hemophilic pseudotumor in the abdomen. Perioperative coagulation factor replacement therapy is also of great significance in reducing the risks and complications.
Efficacy of automated percutaneous lumbar discectomy for lumbar disc herniation in young male soldiers
Authors: Kim Jang Hun , Lee Junki , Lee Won Jae , Shin Dong-Won , Lee Seong-Jong , Roh Haewon , Jeong Hyung Jun , Lee Tae Hoon , Kwon Woo-Keun
Published: November 2019

Lumbar disc herniation (LDH) often results in back pain and radicular pain and is frequently treated with minimally invasive non-surgical methods in Korean Armed Forces Hospitals. Automated percutaneous lumbar discectomy (APLD) has been reported to have good clinical outcomes with low complication rates; however, the clinical efficacy of APLD performed in young male soldiers is uncertain. In order to clarify the efficacy of APLD for the treatment of LDH in young male soldiers, we designed a retrospective case–control study to compare patients who received APLD with patients treated with epidural steroid injection (ESI) alone.

A total of 181 patients were enrolled and divided into the APLD (n = 92) and ESI (n = 89) groups according to the treatment modality. A simple logistic regression analysis was conducted to clarify the difference between the two. To optimize patient selection, APLD group was additionally divided for subgroup analysis into favorable (n = 59) and unfavorable (n = 33) groups based on satisfaction scales. A simple logistic analysis was also performed.

The differences between pre- and postoperative numerical rating scale of pain (P = .0027) and hospital-own satisfaction scale (P = .0045) of the APLD group were significantly better compared to those of the ESI group. In terms of subgroup analysis, single-level pathology (P = 0.244) and protruded disc (P = .0443) were associated with favorable outcomes, whereas dual pathology and extruded disc were related with unfavorable outcomes.

APLD using Dekompressor, performed in young male soldiers with back and radicular pain owing to LDH, showed better clinical outcomes compared to the ESI only therapy. Additionally, a single-level pathology with protruded disc was associated with favorable outcomes and may be indicated for treatment.
Assessment of Serum Galactomannan Test Results of Pediatric Patients With Hematologic Malignancies According to Consecutive Positivity and Threshold Level in Terms of Invasive Aspergillosis Diagnosis: Cross-Sectional Research in a Tertiary Care Hospital
Authors: Çağlar İlknur , Özkerim Duygu , Tahta Neryal , Düzgöl Mine , Bayram Nuri , Demirağ Bengü , Karapinar Tuba H. , Sorguç Yelda , Gözmen Salih , Dursun Vecihe , Oymak Yeşim , Vergin Canan , Devrim İlker
Published: November 2019

The aim of this study was to evaluate the diagnostic utility of serum galactomannan (GM) positivity for invasive aspergillosis (IA) in children. Positive GM results between January 2015 and August 2017 were reviewed retrospectively in children with hematologic malignancies. Single and consecutive positive GM results were evaluated according to the different galactomannan index (GMI) (>0.5, >0.7, >1.0 and >1.5) values. There were 104 positive GM results of 70 patients. IA was identified in 29 patients (41.4%) (2 proven and 27 probable). For a single positive GMI of >0.5, >0.7, >1.0, and >1.5, the numbers were 104, 76, 57, and 32 and the positive predictive values (PPVs) were 39.4%, 43.2%, 47.2%, and 50.0%, respectively. The single GM positivity at different thresholds showed no difference between the IA and non-IA group (P>0.05). For 2 consecutive positive GMI values of >0.5, >0.7, >1.0, and >1.5, the numbers were 34, 20, 13, and 4, and the PPVs were 58.8%, 65.0%, 84.6%, and 100.0%, respectively. In the IA group, positivity was higher at all thresholds (P<0.05). According to our findings, consecutive GM positivity has higher PPVs independently from the cutoff value chosen. In pediatric patients with high risk, consecutive sampling should be preferred.
A Novel Frameshift Mutation in the FGA Gene (c.196 delT) Leading to Congenital Afibrinogenemia
Authors: Aydin Köker Sultan , Köker Alper , Neerman-Arbez Marguerite , Ö. Tunçer Gökçen , Akbas Yilmaz , Kara Tugce T. , Coban Yasemin
Published: November 2019

Background:

Congenital afibrinogenemia is characterized by the absence of fibrinogen. Congenital fibrinogen disorders result from several mutations in FGA, FGB, or FGG. Their epidemiology is not well known.

Observation:

The present study reports on 2 children with congenital afibrinogenemia. The first child, a male who is now 9 years old, was diagnosed with afibrinogenemia after spontaneous intracranial bleeding at the age of 3 years. The second child is a 2-year-old female cousin of the first patient, who was diagnosed with afibrinogenemia after coagulation tests were carried out due to frequent epistaxis and mucocutaneous bleeding. At follow-up, blood samples of the patients and their parents were sent to the Department of Genetic Medicine and Development, University Medical Center, Switzerland, for polymerase chain reaction analysis. In both patients, the novel homozygous frameshift mutation in the FGA exon 3: c.196 delT was detected. The parents of the patients were both heterozygous for the same mutation.

Conclusions:

Congenital afibrinogenemia is a rare coagulation disease. The molecular epidemiology of congenital fibrinogen disorders is complex, and the identification of new mutations will help shed light on this complex molecular structure. Therefore, a genetic analysis that includes more centers is needed.
The Similarities and Differences in Transition to Practice Experiences for New-Graduate RNs and Practical Nurses in Long-term Care
Authors: Whitmore Carly , Baxter Pamela E. , Kaasalainen Sharon , Ploeg Jenny
Published: November 2019

OBJECTIVE

The aim of this study was to describe the transition-to-practice experience of new-graduate nurses (NGNs) in long-term-care (LTC) settings.

BACKGROUND

Transitioning to professional practice is a challenging time for an NGN. This experience is scarcely described for RNs outside of acute care settings and not described for the LPN.

METHODS

A qualitative case study was used to explore the described transition-to-practice experience of new-graduate RNs and LPNs in LTC.

RESULTS

This study revealed that the transition-to-practice experience of new-graduate LPNs was similar to the experience described by RNs. Differences in experience were related to leadership roles in the setting.

CONCLUSIONS

Findings contribute to new understanding of the experience of the NGN in LTC settings. This study reinforces the need for greater support for nursing graduates in this setting.
Sinus of Valsalva Aneurysms
Authors: Shaw Manish , Sharma Arun , Kumar Sanjeev
Published: November 2019

Sinuses of Valsalva aneurysms are rare cardiac anomalies with a varied clinical spectrum. The presentation may range from silent asymptomatic cases detected incidentally to catastrophic rupture. They are associated with potentially fatal complications; however, the prognosis after treatment is excellent, which mandates prompt and accurate diagnosis. Imaging is of paramount importance in diagnosis, treatment planning, and postsurgical follow-up. Echocardiography remains the initial investigation of choice; however, cardiac magnetic resonance imaging and computed tomography are being increasingly utilized as complementary imaging techniques. The latest generation multidetector computed tomography with its improved spatial and temporal resolution provides high-quality reconstructed images with reduced radiation burden. Moreover, it allows the simultaneous assessment of coronary arteries, thereby helping in mapping the ideal treatment option. Surgical repair remains the treatment of choice with percutaneous closure in selected patients.
Sebaceous Nevus of the Scalp
Authors: Goel Pedram , Wolfswinkel Erik M. , Fahradyan Artur , Tsuha Michaela , Hough Michelle , Magee William , Hammoudeh Jeffrey A. , Urata Mark M. , Howell Lori K.
Published: November 2019

Excisions of scalp nevus sebaceous (NS) presents a unique challenge due to limited soft tissue laxity, hair-bearing skin, and convex surfaces which often leave the surgeon and patient underwhelmed with the reconstructive outcome. In this study, the authors conducted an institutional review board-approved retrospective review of patients who underwent excision of pathologically proven scalp primary NS from 2003 to 2017 at our institution to better define the reconstructive outcomes and options for treatment of pediatric scalp NS. 92 patients were included in the study, 54 males (58.7%) and 38 females (41.3%). The average age at surgery was 7.24 years (0.5–16.0; SD 4.7). Local tissue undermining/galeal scoring with primary closure (LTUGS) was used for lesions with average surface area of 3.6 cm2, rotational or transposition flaps (RF/TF) for lesions averaging 4.3 cm2, completed serial excision for lesions averaging 13.9 cm2, and tissue expansion (TE) for lesions averaging 21 cm2 (P <0.001). One or more poor outcomes were experienced by 35 patients (38%), with a significant difference between the surgical groups; LTUGS 37.2% (29/78), RF/TF 60% (3/5), serial excision 100% (3/3), TE 0% (0/6) (P = 0.022). Univariant binary regression analysis within the LTUGS and RF/TF groups showed that lesion size was a significant predictor of poor outcomes (P = 0.012). All specimens in this study were negative for carcinoma. Therefore, most pediatric nevus sebaceous of the scalp can be managed by a single-phase procedure though risk of poor outcomes increase with nevus size with high rates of poor outcomes even with small lesions.
Lisdexamfetamine in Pediatric Binge Eating Disorder: A Retrospective Chart Review
Authors: Guerdjikova Anna I. , Blom Thomas J. , Mori Nicole , Matthews Abigail , Cummings Tracy , Casuto Leah L. , McElroy Susan L.
Published: November 2019

Objectives

The purpose of this retrospective chart review was to evaluate lisdexamfetamine dimesylate (LDX) in the treatment of pediatric binge eating disorder (BED).

Methods

We examined the clinical records of 25 patients, 12 to 19 years of age, who were prescribed LDX and had a diagnosis of BED between 2014 and 2017.

Results

Binge eating disorder in adolescents was highly comorbid with attention deficit hyperactivity disorder, mood and anxiety disorders, and severe obesity. Fifteen participants reported some level of improvement of their BED symptoms with LDX treatment. Posttreatment body mass index (BMI) percentile was not significantly reduced, and all but 2 participants remained in their same BMI classification. Lisdexamfetamine dimesylate treatment duration was not associated with change in BMI percentile, and the medication was well tolerated.

Conclusions

Lisdexamfetamine dimesylate may have clinical utility for BED in adolescents, but randomized, placebo-controlled studies of its efficacy, tolerability, and safety in this population are needed.
Saturnispora mangrovi f.a., sp. nov. from Syhat mangrove, Saudi Arabia
Authors: El-Samawaty Abd El-Rahim M. A. , Boekhout Teun , Yassin Mohamed A. , Abdel-Wahab Mohamed A.
Published: November 2019

Strain SY-07 was isolated from decaying leaves of Avicennia marina collected from Syhat mangroves, Dammam city, Arabian Gulf, Saudi Arabia. Phylogenetic analyses of three genes [D1/D2 region of the LSU and SSU rRNA genes and internal transcribed spacer (ITS) region] showed that strain SY-07 represents a novel species of the genus Saturnispora distinct from closely related species. Saturnispora mendoncae was the most closely related species with an LSU gene sequence similarity of 89.3 % (58 nucleotide substitutions and four indels out of 578 nt), 97 % similarity for the SSU gene (42 nucleotide substitutions and 10 indels out of 1614 nt) and 88 % similarity for the ITS region (15 nucleotide substitutions and eight indels out of 430 nt). In addition, strain SY-07 differed from S. mendoncae by its ability to assimilate d-galactose (weak), d-xylose (weak), meso-erythritol (delayed), glucono-δ-lactone, citrate (delayed) and ethylamine. S. mendoncae produced persistent asci that contain two to four spherical ascospores and lacked pseudohyphae, while sexual reproduction was not observed in strain SY-07 and extensive and pseudohyphae were present. Strain SY-07 was able to grow at between 25 and 40 °C, while S. mendoncae did not grow at 37 °C. The name Saturnispora mangrovi f.a., sp. nov. is proposed for strain SY-07. The holotype is CBS 15874, with the ex-type culture AUMC 12005. The MycoBank number for Saturnispora mangrovi f.a., sp. nov. is MB 827036.
Spatiotemporal Control of CRISPR/Cas9 Function in Cells and Zebrafish using Light-Activated Guide RNA
Authors: Zhou Wenyuan , Brown Wes , Bardhan Anirban , Delaney Michael , Ilk Amber S. , Rauen Randy R. , Kahn Shoeb I. , Tsang Michael , Deiters Alexander
Published: November 2019

We developed a new method for conditional regulation of CRISPR/Cas9 activity in mammalian cells and zebrafish embryos via photochemically activated, caged guide RNAs. Caged gRNAs are generated by substituting four nucleobases evenly distributed throughout the 5’-protospacer region with caged nucleobases during synthesis. Caging confers complete suppression of gRNA:target dsDNA hybridization and rapid restoration of CRISPR/Cas9 function upon optical activation. This tool offers simplicity and complete programmability in design, high spatiotemporal specificity in cells and zebrafish embryos, excellent off to on switching, and stability by preserving the ability to form Cas9:gRNA ribonucleoprotein complexes. caged gRNAs are novel tools for conditional control of gene editing thereby enabling the investigation of spatiotemporally complex physiological events by obtaining a better understanding of dynamic gene regulation.
Cortical state transitions and stimulus response evolve along stiff and sloppy parameter dimensions, respectively
Authors: Ponce-Alvarez Adrián , Mochol Gabriela , Hermoso-Mendizabal Ainhoa , de la Rocha Jaime , Deco Gustavo
Published: November 2019

Previous research showed that spontaneous neuronal activity presents sloppiness: the collective behavior is strongly determined by a small number of parameter combinations, defined as “stiff” dimensions, while it is insensitive to many others (“sloppy” dimensions). Here, we analyzed neural population activity from the auditory cortex of anesthetized rats while the brain spontaneously transited through different synchronized and desynchronized states and intermittently received sensory inputs. We showed that cortical state transitions were determined by changes in stiff parameters associated with the activity of a core of neurons with low responses to stimuli and high centrality within the observed network. In contrast, stimulus-evoked responses evolved along sloppy dimensions associated with the activity of neurons with low centrality and displaying large ongoing and stimulus-evoked fluctuations without affecting the integrity of the network. Our results shed light on the interplay among stability, flexibility, and responsiveness of neuronal collective dynamics during intrinsic and induced activity.
Differences in intake of high-fat high-sugar diet are related to variations in central dopamine in humans
Authors: Hartmann Hendrik , Pauli Larissa K. , Janssen Lieneke K. , Huhn Sebastian , Ceglarek Uta , Horstmann Annette
Published: November 2019

Obesity is associated with alterations in dopaminergic transmission and cognitive function. Recent findings from rodent studies suggest that diets rich in saturated fat and refined sugars (HFS) induce changes in the dopamine system independent of excessive body weight. However, so far the impact of HFS on the human brain has not been investigated. Here, we compared the effect of dietary dopamine depletion on dopamine dependent cognitive tasks between two groups that differ in habitual intake of dietary fat and sugar. Specifically, we used a double-blind within-subject crossover design to compare the effect of acute phenylalanine/tyrosine depletion (APTD) on a reinforcement learning and a working memory task, in two groups that are on opposite ends of the spectrum of self-reported HFS intake (low vs. high intake: LFS vs. HFS group). We tested 31 healthy young women, who were matched for BMI (mostly normal weight to overweight) and IQ. Depletion of central dopamine reduced the working memory specific performance on the operation span task (OSPAN) in the LFS, but not in the HFS group (p = 0.023, r = 0.210). Learning from positive and negative reinforcement (probabilistic selection task: PST) was increased in both diet groups after dopamine depletion (p = 0.048, r = 0.144). As secondary exploratory research question we measured peripheral dopamine precursor availability (pDAP) at baseline as an estimate for central dopamine levels. The HFS group had a significantly higher pDAP at baseline compared to the LFS group (p = .048, r = −0.355). Our data provides first evidence that the intake of HFS is associated with changes in indirect measures of central dopamine levels in humans. The observed associations are independent of body weight status, suggesting that consumption of HFS might be associated with maladaptive behaviors contributing to the development of obesity.
Epithelial Vegfa specifies a distinct endothelial population in the mouse lung
Authors: Ellis Lisandra Vila , Cain Margo P , Hutchison Vera , Flodby Per , Crandall Edward D , Borok Zea , Zhou Bin , Ostrin Edwin J , Wythe Joshua D , Chen Jichao
Published: November 2019

The lung microvasculature is essential for gas exchange and commonly considered homogeneous. We show thatVascular endothelial growth factor A(Vegfa) from the epithelium specifies a distinct endothelial cell (EC) population in the postnatal mouse lung.Vegfais predominantly expressed by alveolar type 1 (AT1) cells and locally required to specify a subset of ECs. Single cell RNA-seq identified 15-20% lung ECs as transcriptionally distinct and marked by Carbonic anhydrase 4 (Car4), which are specifically lost upon epithelialVegfadeletion. Car4 ECs, unlike bulk ECs, have extensive cellular projections and are separated from AT1 cells by a limited basement membrane without intervening pericytes. Without Car4 ECs, the alveolar space is aberrantly enlarged despite the normal appearance of myofibroblasts. Lung Car4 ECs and retina tip ECs have common and distinct transcriptional profiles. These findings support a signaling role of AT1 cells and shed light on alveologenesis.
Electrical propagation of vasodilatory signals in capillary networks
Authors: Lee Pilhwa
Published: November 2019

A computational model is developed to study electrical propagation of vasodilatory signals and arteriolar regulation of blood flow depending on the oxygen tension and agonist distribution in capillary network. The involving key parameters of endothelial cell-to-cell electrical conductivity and plasma membrane area per unit volume were calibrated with the experimental data on an isolated endothelial tube of mouse skeletal feeding arteries. The oxygen saturation parameters in terms of ATP release from erythrocytes are estimated from the data of a left anterior descending coronary blood perfusion of dog. In regard to the acetylcholine induced upstream conduction, our model shows that spatially uniform superfusion of acetylcholine attenuates the electrical signal propagation, and blocking calcium activated potassium channels suppresses that attenuation. On the other hand, local infusion of acetylcholine induces enhanced electrical propagation that corresponds to physiological relevance. In the integration of the endothelial tube and the lumped arterioles vessel model, we show that endothelial purinergic oxygen sensing of ATP released from erythrocytes and local infusion of acetylcholine are all individually effective to induce vasodilatory signals to regulate blood flow in arterioles. We have recapitulated the upstream vasomotion in arterioles from the elevated oxygen tension in the downstream capillary domain. This study is a foundation for characterizing effective pharmaceutical strategies for ascending vasodilation and oxygenation.
EXoO-Tn: Tag-n-Map the Tn Antigen in the Human Proteome
Authors: Yang Weiming , Ao Minghui , Song Angellina , Xu Yuanwei , Zhang Hui
Published: November 2019

Tn antigen (Tn), a single N-acetylgalactosamine (GalNAc) monosaccharide attached to protein Ser/Thr residues, is found on most solid tumors yet rarely detected in adult tissues, featuring it one of the most distinctive signatures of cancers. Although it is prevalent in cancers, Tn-glycosylation sites are not entirely clear owing to the lack of suitable technology. Knowing the Tn-glycosylation sites will spur the development of new vaccines, diagnostics, and therapeutics of cancers. Here, we report a novel technology named EXoO-Tn for large-scale mapping of Tn-glycosylation sites. EXoO-Tn utilizes glycosyltransferase C1GalT1 and isotopically-labeled UDP-Gal(13C6) to tag and convert Tn to Gal(13C6)-Tn, which has a unique mass being distinguishable to other glycans. This exquisite Gal(13C6)-Tn structure is recognized by OpeRATOR that specifically cleaves N-termini of the Gal(13C6)-Tn-occupied Ser/Thr residues to yield site-containing glycopeptides. The use of EXoO-Tn mapped 947 Tn-glycosylation sites from 480 glycoproteins in Jurkat cells. Given the importance of Tn in diseases, EXoO-Tn is anticipated to have broad utility in clinical studies.
Integrating Economic dynamics into Ecological Networks: The case of fishery sustainability
Authors: Glaum Paul , Cocco Valentin , Valdovinos Fernanda S.
Published: November 2019

Summary/Abstract

Understanding and sustainably managing anthropogenic impact on ecosystems requires studying the integrated economic -ecological dynamics driving coupled human-natural systems. Here, we expand ecological network theory to study fishery sustainability by incorporating economic drivers into food-web models to evaluate the dynamics of thousands of single-species fisheries across hundreds of generated food-webs and two management strategies. Analysis reveals harvesting high population biomass species can initially support fishery persistence, but threatens long term economic and ecological sustainability by indirectly inducing extinction cascades in non-harvested species. This dynamic is exacerbated in open access fisheries where profit driven growth in fishing effort increases perturbation strength. Results demonstrate the unique insight into both ecological dynamics and sustainability garnered from considering economically dynamic fishing effort in the network.

One Sentence Summary

Integrating economic drivers into ecological networks reveal non-linear drivers of sustainability in fisheries.
Differential effects of day-night cues and the circadian clock on the barley transcriptome
Authors: Müller Lukas M. , Mombaerts Laurent , Pankin Artem , Davis Seth J. , Webb Alex A. R. , Goncalves Jorge , von Korff Maria
Published: November 2019

The circadian clock is a complex transcriptional network that regulates gene expression in anticipation of the day-night cycle and controls agronomic traits in plants. However, in crops, information on the effects of the internal clock and day-night cues on the transcriptome is limited. We analysed the diel and circadian leaf transcriptomes in the barley cultivar Bowman and derived introgression lines carrying mutations in EARLY FLOWERING 3 (ELF3), LUX1, and EARLY MATURITY 7 (EAM7). Mutations in ELF3 and LUX1 abolished circadian transcriptome oscillations under constant conditions, whereas eam7 maintained oscillations of ≈30% of the circadian transcriptome. However, day-night cues fully restored transcript oscillations in all three mutants and thus compensated for a disrupted oscillator in the arrhythmic barley clock mutants elf3 and lux1. Nevertheless, elf3 but not lux1 affected the phase of the diel oscillating transcriptome and thus the integration of external cues into the clock. Using dynamical modelling, we predicted a structure of the barley circadian oscillator and interactions of its individual components with day-night cues. Our findings provide a valuable resource for exploring the function and output targets of the circadian clock and for further investigations into the diel and circadian control of the barley transcriptome.
Anthropomorphic left ventricular mesh phantom: a framework to investigate the accuracy of SQUEEZ using Coherent Point Drift for the detection of regional wall motion abnormalities
Authors: Manohar Ashish , Colvert Gabrielle , Schluchter Andrew , Contijoch Francisco , McVeigh Elliot R.
Published: November 2019

We present an anthropomorphically accurate left ventricular (LV) phantom derived from human CT data to serve as the ground truth for the optimization and the spatial resolution quantification of a CT-derived regional strain metric (SQUEEZ) for the detection of regional wall motion abnormalities. Displacements were applied to the mesh points of a clinically derived end-diastolic LV mesh to create analytical end-systolic poses with physiologically accurate endocardial strains. Normal function as well as regional dysfunction of four sizes (1, 2/3, 1/2, and 1/3 AHA (American Heart Association) segments as core diameter), each exhibiting hypokinesia (70% reduction in strain) and subtle hypokinesia (40% reduction in strain), were simulated. Regional shortening (RSCT) estimates were obtained by registering the end-diastolic mesh to each simulated end-systolic mesh condition using a non-rigid registration algorithm. Ground-truth models of normal function and of hypokinesia were used to identify the optimal parameters in the registration algorithm, and to measure the accuracy of detecting regional dysfunction of varying sizes and severities. For normal LV function, RSCT values in all 16 AHA segments were accurate to within ±5%. For cases with regional dysfunction, the errors in RSCT around the dysfunctional region increased with decreasing size of dysfunctional tissue.
The Time Varying Networks of the Interoceptive Attention and Rest
Authors: Martínez Ana Y. , Demertzi Athena , Bauer Clemens C.C. , Gracia-Tabuenca Zeus , Alcauter Sarael , Barrios Fernando A.
Published: November 2019

Focused attention to spontaneous sensations is a phenomenon that demands interoceptive abilities and a dynamic character of attentive processes. The lack of its control has been linked to neuropsychiatric disorders, such as illness-anxiety disorder. Regulatory strategies, like focused attention meditation, may enhance the ability to control attention particularly to body sensations, which can be reflected on functional neuroanatomy. Adopting a systems-level approach, we aimed at estimating the recurring fMRI functional connectivity (FC) patterns between regions of the dorsal attention network, default mode network, and frontoparietal network during 20 minutes of an attentional task to spontaneous sensations (Task), and at rest, before (Pre-task rs) and after the task (Post-task rs), in fifteen experienced meditators. Dynamic functional connectivity analysis was performed using sliding windows and k-means clustering on the grouped data finding five FC patterns. In both rest conditions the subjects remain longer in a low connectivity state, in contrast, during the task a higher proportion of time spent in complex organization states was preferred. Moreover, an impact over the post-task rs FC was observed as an effect of the preceding interoceptive task performance, with this remaining effect probably taking an active role in the learning process linked to cognitive training.
Recurrent Neoantigens in Colorectal Cancer as Potential Immunotherapy Targets
Authors: Chen Chao , Liu Songming , Li Bo
Published: November 2019

This study was aimed to investigate the mutations in colorectal cancer (CRC) for recurrent neoantigen identification. A total of 1,779 samples with whole exome sequencing (WES) data were obtained from 7 published CRC cohorts. Common HLA genotypes were used to predict the probability of neoantigens at high frequency mutants in the dataset. Based on the WES data, we not only obtained the most comprehensive CRC mutation landscape so far, but also found 1550 mutation sites which could be identified in at least 5 or more patients, includingKRASG12D (8%),KRASG12V (5.8%),PIK3CAE545K (3.5%),PIK3CAH1047R (2.5%) andBMPR2N583Tfs*44 (2.8%). These mutations can also be recognized by multiple common HLA molecules as potential ‘public’ neoantigens. Many of these mutations also have high mutation rates in metastatic pan-cancers, suggesting their value as therapeutic targets in different cancer types. Overall, our analysis provides recurrent neoantigens as potential cancer immunotherapy targets.
Classification of down-core foraminifera image sets using convolutional neural networks.
Authors: Marchant Ross , Tetard Martin , Pratiwi Adnya , de Garidel-Thoron Thibault
Published: November 2019

Manual identification of foraminifera species or morphotypes under stereoscopic microscopes is time-consuming for the taxonomist, and a long-time goal has been automating this process to improve efficiency and repeatability. Recent advances in computation hardware have seen deep convolutional neural networks emerge as the state-of-the-art technique for image-based automated classification. Here, we describe a method for classifying large down-core foraminifera image set using convolutional neural networks. Construction of the classifier is demonstrated on the publically available Endless Forams image set with an best accuracy of approximately 90%. A complete down-core analysis is performed for benthic species in the Holocene period for core MD02-2518 from the North Eastern Pacific, and the relative abundances compare favourably with manual counting, showing the same signal dynamics. Using our workflow opens the way to automated paleo-reconstruction based on computer image analysis, and can be employed using our labelling and classification software, ParticleTrieur.
Production of Insoluble Starch-Like Granules in Escherichia coli by Modification of the Glycogen Synthesis Pathway
Authors: White Joseph J. , Cain Natasha , French Christopher E.
Published: November 2019

While investigating the conversion of cellulosic biomass to starch-like materials for industrial use, it was observed that the overexpression of native ADP-glucose pyrophosphorylase GlgC in Escherichia coli led to the formation of insoluble polysaccharide granules within the cytoplasm, occupying a large fraction of the cell volume, as well as causing an overall increase in cellular polysaccharide content. TEM microscopy revealed that the granules did not have the lamellar structure of starch, but rather an irregular, clustered structure. On starvation, cells overexpressing GlgC appeared unable to fully degrade their polysaccharide material and granules were still clearly visible in cultures after 8 days of starvation. Interestingly, the additional overexpression of the branching enzyme GlgB eliminated the production of granules and led to a further increase in cellular polysaccharides. GlgC is generally thought to be responsible for the rate-limiting step of glycogen synthesis. Our interpretation of these results is that excess GlgC activity may cause the elongation of glycogen chains to outpace the addition of side branches, allowing the chains of adjacent glycogen molecules to reach lengths at which they spontaneously intertwine, forming dense clusters that are largely inaccessible to the host. However, upon additional upregulation of the GlgB branching enzyme, the branching of the polysaccharide is able to keep speed with the synthesis of linear chains, eliminating the granule phenotype. This study suggests potential avenues for increasing bacterial polysaccharide production and recovery.

Importance

In this work, the polysaccharide stores of Escherichia coli were altered through the addition of extra copies of the bacteria’s own polysaccharide synthesis genes. In this way, bacteria were created that produced over twice the level of storage polysaccharide as a control strain, in the form of a granule that could potentially facilitate easy harvest. Another form of mutant Escherichia coli was created that produced over seven times the normal level of storage polysaccharide, and also grew to higher cell densities in liquid culture. In addition to increasing our understanding of glycogen synthesis, it is proposed that similarly modified bacteria, grown on inexpensive waste materials, may be a useful source of starch-like polysaccharides for industrial or agricultural use. In particular, the use of cyanobacterial glycogen as a carbon source for biofuels has recently been gaining interest, and the work presented here may well be applicable in this field.
Federated queries of clinical data repositories: balancing accuracy and privacy
Authors: Yu Yun William , Weber Griffin M
Published: November 2019

Researchers use large federated clinical data networks that connect dozens of healthcare organizations to access data on millions of patients. However, because patients often receive care from multiple sites in the network, queries frequently double-count patients. Using the probabilistic streaming algorithm HyperLogLog and adding obfuscation, we developed a scalable method for estimating the number of distinct lives that match a query, which balances accuracy and privacy in a “tunable” way.
Inter-subject phase synchronization differentiates neural networks underlying physical pain empathy
Authors: Xu Lei , Bolt Taylor , Nomi Jason S. , Li Jialin , Zheng Xiaoxiao , Fu Meina , Kendrick Keith M. , Becker Benjamin , Uddin Lucina Q.
Published: November 2019

Recent approaches for understanding the neural basis of pain empathy emphasize the dynamic construction of neural networks underlying this multifaceted social cognitive process. Inter-subject phase synchronization (ISPS) is an approach for exploratory analysis of task-based fMRI data that reveals brain networks dynamically synchronized to task-features across participants. We applied ISPS to task-fMRI data assessing vicarious pain empathy in a large sample of healthy participants (n=238). The task employed physical (limb) and affective (faces) painful and corresponding non-painful visual stimuli. ISPS revealed two distinct networks synchronized during physical pain observation, one encompassing anterior insula and midcingulate regions strongly engaged in (vicarious) pain, and another encompassing parietal and inferior frontal regions associated with social cognitive processes which may further modulate and support the physical pain empathic response. No robust network synchronization was observed while processing affective pain, possibly reflecting high inter-individual variation in response to socially transmitted pain experiences. ISPS also revealed networks related to task onset or general processing of physical (limb) or affective (face) stimuli which encompassed networks engaged in object manipulation or face processing, respectively. Together, the ISPS approach permits segregation of networks engaged in different psychological processes, providing additional insight into shared neural mechanisms of empathy for physical pain, but not affective pain, across individuals.
Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque responses
Authors: Oggero S , de Gaetano M , Marcone S , Barry M , Montero-Melendez T , Cooper D. , Norling L V , Brennan E P , Godson G , Perretti M
Published: November 2019

In atherosclerosis, a chronic disease characterized by lipid accumulation, fibrosis and vascular inflammation, extracellular vesicles (EVs) are emerging as key players in different stages of disease development. Here we provide evidence that EVs released by mixed aggregates of monocytes and platelets in response to TNF-α are both CD14+ and CD41+. Tempering platelet activation with Iloprost™ impacted the quality and quantity of EV produced. Proteomics of EVs from cells activated with TNF-α alone or in presence Iloprost™ revealed distinct proteome, with selective hits like gelsolin. EVs from TNF-α stimulated monocytes augmented release of cytokines, and modulated more than 500 proteins by proteomics, when added to human atherosclerotic plaques. In contrast, EVs generated by TNF-α and Iloprost™ produced minimal plaque activation. In conclusion, attenuating platelet activation has an effect on EV composition released from monocyte/platelet aggregates with downstream modulation of their pro-inflammatory actions and contribution to the development and progression of atherosclerosis.
Comparative Genomics and Full-Length TprK Profiling ofTreponema pallidumsubsp.pallidumReinfection
Authors: Addetia Amin , Tantalo Lauren C. , Lin Michelle J. , Xie Hong , Huang Meei-Li , Marra Christina M. , Greninger Alexander L.
Published: November 2019

Developing a vaccine againstTreponema pallidumsubspeciespallidum, the causative agent of syphilis, remains a public health priority. Syphilis vaccine design efforts have been complicated by lack of an in vitroT. pallidumculture system, prolific antigenic variation in outer membrane protein TprK, and lack of functional annotation for nearly half of the genes. Understanding the genetic basis ofT. pallidumreinfection can provide insights into variation among strains that escape cross-protective immunity. Here, we present comparative genomic sequencing and deep, full-lengthtprKprofiling of twoT. pallidumisolates from blood from the same patient that were collected six years apart. Notably, this patient was diagnosed with syphilis four times, with two of these episodes meeting the definition of neurosyphilis, during this interval. Outside of the highly variabletprKgene, we identified 14 coding changes in 13 genes. Nine of these genes putatively localized to the periplasmic or outer membrane spaces, consistent with a potential role in serological immunoevasion. Using a newly developed full-lengthtprKdeep sequencing protocol, we profiled the diversity of this gene that far outpaces the rest of the genome. Intriguingly, we found that the reinfecting isolate demonstrated less diversity across eachtprKvariable region compared to the isolate from the first infection. Notably, the two isolates did not share any full-length TprK sequences. Our results are consistent with an immunodominant-evasion model in which the diversity of TprK explains the ability ofT. pallidumto successfully reinfect individuals, even when they have been infected with the organism multiple times.

Author Summary

The causative agent of syphilis,Treponema pallidumsubspeciespallidum, is capable of repeat infections in people, suggesting that the human immune response does not develop sufficiently broad or long-lasting immunity to cover treponemal diversity. Here, we examined the genomes from two blood-derived isolates ofT. pallidumderived 6 years apart from a patient who had syphilis four times during the same period to understand the genetic basis of reinfection. We found a paucity of coding changes across the genome outside of the highly variabletprKgene. Using deep profiling of the full-lengthtprKgene, we found surprisingly that the two isolates did not share any full-length TprK sequences.