bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-Related Risk Factors for Worsened Abdominal Well-Being after Autologous Breast Reconstruction
Authors: Stone Jill P. , Bello Ricardo J. , Siotos Charalampos , Meyer Meredith L. , Sebai Mohamad E. , Payne Rachael M. , Manahan Michele A. , Cooney Damon S. , Sacks Justin M. , Broderick Kristen P. , Cooney Carisa M. , Rosson Gedge D.
Published: December 2019

Background:

Patient-reported lower satisfaction with the abdomen preoperatively is a strong predictor of undergoing DIEP flap surgery. The authors evaluated physical well-being of the abdomen before and after flap-based breast reconstruction to determine potential predictors for decreased postoperative abdominal well-being.

Methods:

The authors retrospectively analyzed an institutional breast reconstruction registry, selecting patients who underwent abdominally based autologous flap breast reconstruction from 2010 to 2015. The authors’ primary outcome was the Physical Well-being of the Abdomen domain from the BREAST-Q, measured preoperatively and at 6- and 12-month follow-up visits after final reconstruction. The authors classified two patient groups: those who experienced a clinically important worsening of Physical Well-being of the Abdomen score and those who did not. The authors used the chi-square test, t test, and Wilcoxon rank sum test, and multivariable logistic regression to identify potential predictors.

Results:

Of 142 women identified, 74 (52 percent) experienced clinically important worsening of physical well-being of the abdomen, whereas 68 (48 percent) did not. The first group experienced a 25-point (95 percent CI, 22 to 28) decrease and the latter an 8-point (95 percent CI, 5 to 10) decrease in score compared to baseline. Multivariable analysis showed an association between higher baseline score and race, with higher odds of decreased score at the 12-month follow-up. A higher baseline RAND-36 general health score, bilateral reconstruction, and a lower body mass index demonstrated a trend for clinically important worsening of physical well-being of the abdomen.

Conclusions:

More than half of flap-based breast reconstruction patients experienced clinically important worsening of abdominal well-being after final breast reconstruction. Clinicians may use these findings to identify patients at higher risk of worsened postoperative abdominal well-being.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Occurrence of Symptomatic Hypotension in Patients Undergoing Breast Free Flaps: Is Enhanced Recovery after Surgery to Blame?
Authors: Anolik Rachel A. , Sharif-Askary Banafsheh , Hompe Eliza , Hopkins Thomas J. , Broadwater Gloria , Hollenbeck Scott T.
Published: December 2019

Background:

Enhanced recovery after surgery (ERAS) initiatives improve postoperative function and expedite recovery, leading to a decrease in length of stay. The authors noted a high rate of postoperative symptomatic hypotension in patients undergoing abdominal free flap breast reconstruction and wished to explore this observation.

Methods:

Subjects undergoing abdominal free flap breast reconstruction at the authors’ institution from 2013 to 2017 were identified. The ERAS protocol was initiated in 2015 at the authors’ hospital; thus, 99 patients underwent traditional management and 138 patients underwent ERAS management. Demographics and perioperative data were collected and analyzed. Postoperative symptomatic hypotension was defined as mean arterial pressure below 80 percent of baseline with symptoms requiring evaluation.

Results:

A significantly higher rate of postoperative symptomatic hypotension was observed in the ERAS cohort compared with the traditional management cohort (4 percent versus 22 percent; p < 0.0001). Patients in the ERAS cohort received significantly less intraoperative intravenous fluid (4467 ml versus 3505 ml; p < 0.0001) and had a significantly increased amount of intraoperative time spent with low blood pressure (22 percent versus 32 percent; p =0.002). Postoperatively, the ERAS cohort had significantly lower heart rate (77 beats per minute versus 88 beats per minute; p < 0.0001) and mean arterial pressure (71 mmHg versus 78 mmHg; p < 0.0001), with no difference in urine output or adverse events.

Conclusions:

The authors report that ERAS implementation in abdominal free flap breast reconstruction may result in a unique physiologic state with low mean arterial pressure, low heart rate, and normal urine output, resulting in postoperative symptomatic hypotension. Awareness of this early postoperative finding can help better direct fluid resuscitation and prevent episodes of symptomatic hypotension.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Pediatric Tissue Expansion: Predictors of Premature Expander Removal in a Single Surgeon’s Experience with 472 Expanders
Authors: Wang Howard D. , Ibrahim Zuhaib , Quan Amy , Bai Jennifer , Ostrander Benjamin T. , Redett Richard J.
Published: December 2019

Background:

Tissue expansion is used for soft-tissue reconstruction in pediatric patients. The expansion process can be complicated by infection and extrusion, leading to premature expander removal. The aim of this study was to identify risk factors associated with premature expander removal caused by infection or extrusion in pediatric patients.

Methods:

A retrospective study of pediatric patients who underwent tissue expansion performed by the senior author (R.J.R.) over a 12-year period was performed. Predictor variables included age, sex, race, indication, anatomical location, number of expanders, serial expansion, and expander size. Bivariate and multivariate analyses were performed to identify risk factors for premature expander removal.

Results:

A total of 139 patients with 472 expanders were included in this study. Complications occurred with 78 expanders (16.5 percent). Premature expander removal caused by infection or exposure occurred with 51 expanders (10.8 percent). In terms of location, the highest rates of premature removal occurred in the lower extremity (20.0 percent) and scalp (16.3 percent). Multivariate analysis identified younger age (0 to 6 years compared with 13 to 17 years; OR, 3.98; 95 percent CI, 1.13 to 14.08; p = 0.03), greater number of expanders (OR, 1.45; 95 percent CI, 1.03 to 2.03; p = 0.03), and lower extremity location (OR, 4.27; 95 percent CI, 1.45 to 12.53; p = 0.008) were associated with an increased odds of premature expander removal.

Conclusions:

Expander removal occurred in approximately 10 percent of tissue expanders. Odds of premature removal is increased with younger age, greater number of expanders, and lower extremity location.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.
Three-Dimensional Topographic Surface Changes in Response to Volumization of the Lateral Suborbicularis Oculi Fat Compartment
Authors: Schreiber Jillian E. , Stern Carrie S. , Jelks Elizabeth B. , Jelks Glenn W. , Tepper Oren M.
Published: December 2019

Background:

Autologous fat grafting is an increasingly preferred method for aesthetic facial rejuvenation. The authors’ group previously described the concept of “lipotopography” as topographic surface changes that occur with fat grafting to discrete facial fat compartments. The purpose of this study was to define the “augmentation zone” of the lateral suborbicularis oculi fat compartment to understand the topographical surface changes following augmentation.

Methods:

Nine cadaver hemifaces were injected with fat analogue at intervals from 1 to 4 cc. Three-dimensional photographs were taken at baseline and following each 1-cc incremental injection. The interval surface changes were calculated using three-dimensional software including perimeter, diameter, and projection.

Results:

The augmentation zone of the lateral suborbicularis oculi fat compartment was characterized by a consistent shape and boundary. The shape was an elongated oval bound superiorly by the lid-cheek junction and inferiorly at the level of the zygomaticocutaneous ligament. Vertical and horizontal diameter and perimeter showed initial increases between 1 and 2 cc and then a plateau between 2 and 3 cc. Projection changes demonstrated an initial slow increase from 1 to 2 cc injection followed by nearly linear growth from 2 to 4 cc.

Conclusions:

Three-dimensional photography and computer analysis provide tools to understand the surface anatomy change in response to fat grafting specific facial fat compartments. Targeted volumization of the lateral suborbicularis oculi fat compartment also results in a unique surface change with consistent shape and anatomical boundaries. The lid-cheek junction and zygomaticocutaneous ligament were observed to restrict the expansion of fat analogue for all injection volumes.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Psychological Resilience and Vulnerability as Mediators Between Adverse Life Events and Fatigue, Motor Dysfunction, and Paresthesia in Multiple Sclerosis
Authors: Swanepoel Isabelle , van Staden Werdie , Fletcher Lizelle
Published: December 2019

Objective

Adverse life events have been associated with exacerbating multiple sclerosis (MS) symptoms, but results have been variable, raising the question on the role of other psychological factors. This study examined the role of psychological resilience and vulnerability as mediators between adverse life events on MS symptoms.

Methods

Participants with MS (N = 1239) were aged 18 to 81 years (mean [SD] = 45.6 [10.4] years), and 84.5% were female. MS symptoms were measured by the modified Fatigue Severity Scale, modified Fatigue Assessment Scale, Motor Dysfunction Assessment Scale, Paraesthesiae Spell Duration Scale, and the Paraesthesiae Cumulative Duration Scale. Psychological measures included the Connor-Davidson Resilience Scale, Resilience Scale for Adults, Psychological Vulnerability Scale, the vulnerability section of the Defence Style Questionnaire, and the Adverse Life Events Assessment Scale. Regression analyses and structural equation modeling were performed.

Results

Adverse life events during the preceding 60 days were associated with fatigue, motor dysfunction, and paresthesia, but with small effect sizes (β from 0.07 to 0.15; p ≤ .014). A structural equation model by which resilience mediated less and vulnerability more MS symptoms after adverse life events during the preceding 60 days showed a statistically significant fit with the data of a moderate to good degree (p < .001; goodness-of-fit statistic = 0.725; root mean square error of approximation = 0.047). Vulnerability played a markedly larger role than did resilience.

Conclusion

The results suggest that psychological resilience and vulnerability play mediating roles in the relation between adverse life events and MS symptoms, but other psychological factors also need to be investigated.
Stressed-Out Oral Immunity: A Gateway From Socioeconomic Adversity to Periodontal Disease
Authors: Gomaa Noha , Glogauer Michael , Nicolau Belinda , Tenenbaum Howard , Siddiqi Arjumand , Fine Noah , Quiñonez Carlos
Published: December 2019

Objective

It has been suggested that adverse socioeconomic conditions “get under the skin” by eliciting a stress response that can trigger periodontal inflammation. We aimed to a) estimate the extent to which socioeconomic position (SEP) is associated with periodontal disease (PD) and proinflammatory oral immunity, and b) determine the contribution of psychosocial stress and stress hormones to these relationships.

Methods

In this cross-sectional study (n = 102), participants (20–59 years old) completed financial and perceived stress questionnaires and underwent full-mouth periodontal examinations. SEP was characterized by annual household income and educational attainment. Cortisol, a biological correlate of chronic stress, was assessed in hair samples. Oral immunity was characterized by assessing oral inflammatory load and proinflammatory oral neutrophil function. Blockwise Poisson and logistic regression models were applied.

Results

Compared with lower SEP, individuals in the middle- and higher-income categories had a significantly lower probability of PD (incidence rate ratio [IRR] = 0.5 [confidence interval {CI} = 0.3–0.7] and IRR = 0.4 [95% CI = 0.2–0.7]) and oral inflammatory load (IRR = 0.6 [95% CI = 0.3–0.8] and IRR = 0.5 [95% CI = 0.3–0.7]) and were less likely to have a proinflammatory oral immune function (odds ratio [OR] = 0.1 [95% CI = 0.0–0.7] and OR = 0.1 [95% CI = 0.0–0.9]). PD and oral immune parameters were significantly associated with financial stress and cortisol. Adjusting for financial stress and cortisol partially attenuated the socioeconomic differences in PD to IRR = 0.7 (95% CI = 0.5–0.8) and IRR = 0.6 (95% CI = 0.5–0.7) for the middle- and higher-income categories, respectively. Similar results were observed for proinflammatory immunity (OR = 0.2 [95% CI = 0.0–1.8] and OR = 0.3 [95% CI = 0.0–2.3]).

Conclusion

These findings suggest that psychosocial stress may contribute to a proinflammatory immunity that is implicated in PD pathobiology and provide insight into social-to-biological processes in oral health.
A Comparative Study on the Effects of High-Intensity Focused Electromagnetic Technology and Electrostimulation for the Treatment of Pelvic Floor Muscles and Urinary Incontinence in Parous Women: Analysis of Posttreatment Data
Authors: Silantyeva Elena , Zarkovic Dragana , Astafeva Evgeniia , Soldatskaia Ramina , Orazov Mekan , Belkovskaya Marina , Kurtser Mark ,   Academician of the Russian Academy of Sciences
Published: December 2019

Objectives

Pelvic floor muscles (PFMs) weakening and urinary incontinence (UI) represent health issues that have a negative impact on daily life. This study compares the immediate efficiency of high-intensity focused electromagnetic (HIFEM) therapy and electrostimulation for the treatment of weakened PFMs, accompanied by the UI.

Methods

Ninety-five parous women were considered for the study. Symptomatic patients received either HIFEM or electrostimulation treatment. Treated patients completed 10 therapies scheduled 2 to 3 times per week (HIFEM) or every other day (electrostimulation). Patients underwent examination by 3-dimensional transperienal ultrasound at the baseline and posttreatments. Levator-urethra gap, anteroposterior diameter, laterolateral diameter of levator hiatus, and hiatal area were measured. In addition, Pelvic Floor Disability Index 20 questionnaire and subjective evaluation of patient’s intimate health were assessed.

Results

Enrolled patients were divided into group I (n = 50, HIFEM), group II (n = 25, electrostimulation), and group III (n = 20, control) according the indication and treatment modality. Three-dimensional ultrasounds showed positive changes in dynamics of the pelvic floor posttreatment (decreased anteroposterior diameter, laterolateral diameter, and hiatal area). However, the significant (P < 0.05) changes of pelvic floor integrity were observed only in group I. In addition, group I achieved greater level of improvement in Pelvic Floor Disability Index 20 questionnaire compared with group II (52% and 18% respectively; P < 0.001). Substantially fewer patients in group I reported urine leakage after treatments.

Conclusions

Posttreatment results suggest that HIFEM technology is suitable for treatment of PFMs weakening and showed to be more effective when compared with electrostimulation in short-term. Therefore, we recommend HIFEM as treatment option for weakened PFMs and UI.
Use of Online Focus Groups for Nutrition and Health Studies
Authors: Jiang Qianzhi , Cohen Nancy L.
Published: December 2019

Online focus groups (OFGs) in health research allow researchers to gain insight into sensitive health topics, reach people with disabilities, and overcome geographic, physical, and medical limitations in data collection. The OFGs can be held synchronously in real time with all participants online simultaneously, or asynchronously, enabling participants to join at their convenience. In this article, we compare OFGs with face-to-face focus groups in nutrition and health-related research with respect to administration and data quality retrieval. As part of a multistate research project on assessment of the nutrition environment for older adults that used OFGs, the researchers' firsthand review experience and lessons learned are discussed.
Salinibius halmophilus gen. nov., sp. nov., isolated from a marine solar saltern
Authors: Ling Si-Kai , Zhang Hui , Wang Nan-Nan , Chen Guan-Jun , Du Zong-Jun
Published: December 2019

A novel Gram-stain-negative, facultatively anaerobic, flagellated and spiral-shaped bacterium, designated WDS2A16AT was isolated from a marine solar saltern in Weihai, PR China. Growth was observed at 20–40 °C (optimal 33–37 °C), 1–15 % (w/v) NaCl (optimal 3–4 %) and pH 6.0–9.0 (optimal pH 7.5). Major cellular fatty acids (>10 %) were C18 : 1ω7c and C16 : 0. Phosphatidylglycerol, diphosphatidylglycerol and an unidentified glycolipid were detected as the predominant polar lipids. The sole respiratory quinone was Q-8. The DNA G+C content of strain WDS2A16AT was 48.5 mol%. The 16S rRNA gene sequence similarities of WDS2A16AT with other species were less than 91 %. The average nucleotide identity, in silico DNA–DNA hybridization and amino acid identity of strain WDS2A16AT with the most related strain

Gynuella sunshinyii

YC6258 T were 66.1, 19.3 and 48.1 %, respectively. Comparative analysis of 16S rRNA gene sequences and phenotypic characterization indicated that strain WDS2A16AT represents a novel species in a new genus, for which the name Salinibius halmophilus gen. nov., sp. nov. is proposed. The type strain is WDS2A16AT (=KCTC 52225T=MCCC 1H00139T).
Roseomonas vastitatis sp. nov. isolated from Badain Jaran desert in China
Authors: Zhao Li-Li , Deng Yang , Sun Ye , Liu Hong-Yu , Yu Li-Yan , Zhang Yu-Qin
Published: December 2019

A Gram-stain-negative, non-motile, coccobacillus-shaped bacterium, designated CPCC 101021T, was isolated from a sandy soil sample collected from Badain Jaran desert, China. Its 16S rRNA gene sequence was closely related to those of members of the genus Roseomonas, showing high similarities with

Roseomonas hibiscisoli

THG-N2.22T (98.0 %),

Roseomonas oryzae

KCTC 42542T (97.9 %),

Roseomonas rhizosphaerae

YW11T (97.9 %) and

Roseomonas suffusca

S1T (97.8 %). In the phylogenetic tree based on 16S rRNA gene sequences, strain CPCC 101021T formed a distinct subclade with

R. oryzae

KCTC 42542T within the genus

Roseomonas

. Growth of the isolate occurred at 15–37 °C and pH 6.0–8.5, with optimal growth at 30 °C and pH 7.0. The major cellular fatty acids were C18 : 1ω7c, summed feature 8 (C16 : 1ω7c/C16 : 1ω6c), summed feature 3 (C16 : 1ω6c/C16 : 1ω7c) and C16 : 0ω6c. Q-10 was detected as the main component in the respiratory quinone system, with Q-9 as a minor component. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, an unidentified phospholipid, an unidentified aminolipid and an unidentified glycolipid were found in the polar lipid profile. The genomic DNA G+C content was 68.7 mol%. The average nucleotide identity was 84.6 % when comparing the draft genome sequences of strain CPCC 101021T with

R. oryzae

KCTC 42542T. On the basis of genotypic, chemotaxonomic and phenotypic characteristics, strain CPCC 101021T is proposed to represent a novel species of the genus

Roseomonas

with the name Roseomonas vastitatis sp. nov. Strain CPCC 101021T (=J1A743T=KCTC 62043T) is the type strain of the species.
Tessaracoccus antarcticus sp. nov., a rhodopsin-containing bacterium from an Antarctic environment and emended description of the genus Tessaracoccus
Authors: Zhou Liu-Yan , Zhang Jin-Yu , Chen Xu-Yang , Du Zong-Jun , Mu Da-shuai
Published: December 2019

A Gram-stain-positive, facultatively anaerobic bacterium, strain JDX10T, was isolated from a soil sample of Fildes Peninsula, Antarctica. Cells of the strain were irregular rod-shaped and non-motile. Cells grew at 4–40 °C (optimum, 28 °C), at pH 6.0–9.0 (optimum, 7.5) and with 0.0–3.0 % (w/v) NaCl (optimum, 1.0 %). According to phylogenetic analysis based on 16S rRNA gene sequences, strain JDX10T was associated with the genus

Tessaracoccus

, and showed highest similarities to

Tessaracoccus rhinocerotis

CCTCC AB 2013217T (97.2 %),

Tessaracoccus flavescens

SST-39T (96.9 %) and

Tessaracoccus terricola

JCM 32157T (96.9 %). The average nucleotide identity scores of strain JDX10T to

T. rhinocerotis

CCTCC AB 2013217T and

T. bendigoensis

JCM 13525T were 74.8 and 73.3 %, respectively and the Genome-to-Genome Distance Calculator scores were 19.2 and 18.7 %, respectively. The major (>10.0 %) cellular fatty acid was anteiso-C15 : 0. The predominant isoprenoid quinone was MK-10(H4). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and one unidentified glycolipid. The phylogenetic analysis and physiological and biochemical data showed that strain JDX10T should be classified as representing a novel species in the genus

Tessaracoccus

, for which the name Tessaracoccus antarcticus sp. nov. is proposed. The type strain is JDX10T (=MCCC 1H00351T=KCTC 49242T).
Bifidobacterium tibiigranuli sp. nov. isolated from homemade water kefir
Authors: Eckel Viktor P. L. , Ziegler Lisa-Marie , Vogel Rudi F. , Ehrmann Matthias
Published: December 2019

Two Bifidobacterium strains, TMW 2.2057Tand TMW 2.1764 were isolated from two different homemade water kefirs from Germany. Both strains were oxidase- and catalase-negative and Gram-staining-positive. Cells were non-motile, irregular rods that were aerotolerant anaerobes. On basis of fructose 6-phosphate phosphoketolase activity, they were assigned to the family Bifidobacteriaceae. Comparative analysis of 16S rRNA and concatenated housekeeping genes (clpC,dnaB,dnaG,dnaJ,hsp60andrpoB) demonstrated that both strains represented a member of the genusBifidobacterium, withBifidobacterium subtileDSM 20096Tas the closest phylogenetic relative (98.35 % identity). Both strains can be distinguished using randomly amplified polymorphic DNA fingerprinting. Analysis of concatenated marker gene sequences as well as average nucleotide identity byblast(ANIb) and﻿in silicoDNA﻿–DNA hybridization (isDDH) calculations of their genome sequences confirmedBifidobacterium subtileDSM 20096Tas the closest relative (87.91 and 35.80 % respectively). All phylogenetic analyses allow differentiation of strains TMW 2.2057Tand TMW 2.1764 from all hitherto described species of the genusBifidobacteriumwith validly published names. We therefore propose a novel species with the nameBifidobacterium tibiigranuli, for which TMW 2.2057T(=DSM 108414T=LMG 31086T) is the type strain.
Comparative genomic analysis identifies X-factor (haemin)-independent Haemophilus haemolyticus: a formal re-classification of 'Haemophilus intermedius'
Authors: Harris Tegan M. , Price Erin P. , Sarovich Derek S. , Nørskov-Lauritsen Niels , Beissbarth Jemima , Chang Anne B. , Smith-Vaughan Heidi C.
Published: December 2019

The heterogeneous and highly recombinogenic genus

Haemophilus

comprises several species, some of which are pathogenic to humans. All share an absolute requirement for blood-derived factors during growth. Certain species, such as the pathogen

Haemophilus influenzae

and the commensal

Haemophilus haemolyticus

, are thought to require both haemin (X-factor) and nicotinamide adenine dinucleotide (NAD, V-factor), whereas others, such as the informally classified ‘Haemophilus intermedius subsp. intermedius’, and

Haemophilus parainfluenzae

, only require V-factor. These differing growth requirements are commonly used for species differentiation, although a number of studies are now revealing issues with this approach. Here, we perform large-scale phylogenomics of 240

Haemophilus

spp. genomes, including five ‘H. intermedius’ genomes generated in the current study, to reveal that strains of the ‘H. intermedius’ group are in fact haemin-independent

H. haemolyticus

(hiHh). Closer examination of these hiHh strains revealed that they encode an intact haemin biosynthesis pathway, unlike haemin-dependent

H. haemolyticus

and

H. influenzae

, which lack most haemin biosynthesis genes. Our results suggest that the common ancestor of modern-day

H. haemolyticus

and

H. influenzae

lost key haemin biosynthesis loci, likely as a consequence of specialized adaptation to otorhinolaryngeal and respiratory niches during their divergence from

H. parainfluenzae

. Genetic similarity analysis demonstrated that the haemin biosynthesis loci acquired in the hiHh lineage were likely laterally transferred from a

H. parainfluenzae

ancestor, and that this event probably occurred only once in hiHh. This study further challenges the validity of phenotypic methods for differentiating among

Haemophilus

species, and highlights the need for whole-genome sequencing for accurate characterization of species within this taxonomically challenging genus.
Landscape of gene expression variation of natural isolates of Cryptococcus neoformans in response to biologically relevant stresses
Authors: Yu Chen-Hsin , Chen Yuan , Desjardins Christopher A. , Tenor Jennifer L. , Toffaletti Dena L. , Giamberardino Charles , Litvintseva Anastasia , Perfect John R. , Cuomo Christina A.
Published: December 2019

Cryptococcus neoformans is an opportunistic fungal pathogen that at its peak epidemic levels caused an estimated million cases of cryptococcal meningitis per year worldwide. This species can grow in diverse environmental (trees, soil and bird excreta) and host niches (intracellular microenvironments of phagocytes and free-living in host tissues). The genetic basic for adaptation to these different conditions is not well characterized, as most experimental work has relied on a single reference strain of C. neoformans. To identify genes important for yeast infection and disease progression, we profiled the gene expression of seven C. neoformans isolates grown in five representative in vitro environmental and in vivo conditions. We characterized gene expression differences using RNA-Seq (RNA sequencing), comparing clinical and environmental isolates from two of the major lineages of this species, VNI and VNBI. These comparisons highlighted genes showing lineage-specific expression that are enriched in subtelomeric regions and in lineage-specific gene clusters. By contrast, we find few expression differences between clinical and environmental isolates from the same lineage. Gene expression specific to in vivo stages reflects available nutrients and stresses, with an increase in fungal metabolism within macrophages, and an induction of ribosomal and heat-shock gene expression within the subarachnoid space. This study provides the widest view to date of the transcriptome variation of C. neoformans across natural isolates, and provides insights into genes important for in vitro and in vivo growth stages.
Ambient pH regulates secretion of lipases in Malassezia furfur
Authors: Juntachai Weerapong , Chaichompoo Athipat , Chanarat Sittinan
Published: December 2019

Malassezia is a lipophilic cutaneous commensal yeast and associated with various skin disorders. The yeast also causes bloodstream infection via intravascular catheters and can be detected even in human gut microbiota. Ambient pH is one of the major factors that affect the physiology and metabolism of several pathogenic microorganisms. Although dynamic changes of pH environment in different parts of the body is a great challenge for Malassezia to confront, the role that ambient pH plays in Malassezia is largely unknown. In this study, we investigated the impact of ambient pH on physiology and expression of lipases in M. furfur grown under different pH conditions. The yeast was able to grow in media ranging from pH 4 to 10 without morphological alteration. Elevation in pH value enhanced the extracellular lipase activity but decreased that of intracellular lipase. The qPCR results revealed that a set of functional lipase genes, LIP3-6, were constitutively expressed regardless of pH conditions or exposure time. Based on the data, we conclude that the external pH plays a promotional role in the secretion of lipases but exerts less effect on transcription of the genes and morphology in M. furfur.
Mechanical model of muscle contraction. 1. Force-velocity relationship
Authors: Louvet S.
Published: December 2019

The two parameters that determine the functionality of a skeletal muscle fiber are the tension (T) exerted at its two endpoints and the shortening speed (V), two mechanical characteristics. We established a relationship between T and V by developing a theoretical model of muscle contraction based on the swinging lever arm hypothesis. At the nanoscale, force and movement are generated by the myosin II heads during the working stroke (WS). The change in conformation of a myosin head during the WS is characterized by the rotation of the lever correlated to the linear displacement of the motor domain. The position of the lever is marked by the angle θ. The maximum variation of θ between the two limits θupand θdownrelating to the two positionsupanddownis usually given equal to 70°. When the angle θ is between θupand θdown, the WS is triggered in three modes, fast, slow or very slow. During the isometric tetanus plateau, θ is uniformly distributed between the two angles θup and θTseparated by a usual difference of 50°. Consequently during isometric tetanus plateau there is a 20° interval between θTand θdownwhere no head is found in WS. We link this absence to the slow detachment of the heads whose orientation of the levers is between θTand θdownduring the rise to the isometric tetanus plateau. The equation between T and V refers to these four occurrences: fast, slow or very slow initiations of the WS between θupand θdown, then slow detachment between θTand θdown. The equation is constructed from the geometric data of the myosin head and the time constants of the cross-bridge cycle reactions associated with these four events. The biphasic aspect of the curve is explained by the slow detachment that occurs only at very slow speeds. An additional term, derived from the viscosity present as soon as the velocity increases completes the equation. An adequate fit between the model and examples from the physiological literature is found (r2> 99%).
Mechanical model of muscle contraction. 5. Tension rise after phase 1 of a length step
Authors: Louvet S.
Published: December 2019

The theoretical approaches developed in accompanying Papers 1 to 3 lead to calculations of the isometric tetanus tension (T0) and the minimum tension (T1) observed at the end of phase 1 of a length step where the fiber is shortened (see Paper 4). During the next three phases, the time rise of the tension (T), from T1 to T0, is determined for any step (see Supplement S5.K). The tension T is expressed as a master equation which is the sum of five terms: (a) T1, (b) a positive or zero contribution resulting from the relaxation induced by the disappearance of the viscosity forces present during phase 1, (c) a positive contribution of elastic origin resulting from the new myosin II heads initiating a working stroke (WS) in the blank areas, (d) a negative contribution caused by the fast detachment of the heads still strongly attached and whose orientation of the levers is beyond theupposition, (e) a negative contribution caused by the slow detachment of WS heads whose orientation of the levers is close to theupposition. An agreement between the model equation and the experimental results referenced in the physiological literature is proven (r2>97.5%). The kinetics of each of the theoretical curves make it possible to distinguish phases 2, 3 and 4 characteristics of the tension rise to T0. The criteria defined to describe the tension at the end of phase 2 (T2) are applied to the master equation. There is an adequate adjustment between the theoretical and experimental T2 values for shortenings less than 8 nm in modulus (r2> 97%).
Correction of amyotrophic lateral sclerosis related phenotypes in induced pluripotent stem cell-derived motor neurons carrying a hexanucleotide expansion mutation inC9orf72by CRISPR/Cas9 genome editing using homology-directed repair
Authors: Ababneh Nidaa , Scaber Jakub , Flynn Rowan , Douglas Andrew , Turner Martin R. , Sims David , Dafinca Ruxandra , Cowley Sally A. , Talbot Kevin
Published: December 2019

The G4C2 hexanucleotide repeat expansion (HRE) inC9orf72is the commonest cause of familial amyotrophic lateral sclerosis (ALS). A number of different methods have been used to generate isogenic control lines using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 and non-homologous end-joining (NHEJ) by deleting the repeat region with the risk of creating indels and genomic instability. In this study we demonstrate complete correction of an induced pluripotent stem cell (iPSC) line derived from aC9orf72-HRE positive ALS/FTD patient using CRISPR/Cas9 genome editing and homology directed repair (HDR), resulting in replacement of the excised region with a donor template carrying the wild-type repeat size to maintain the genetic architecture of the locus. The isogenic correction of theC9orf72HRE restored normal expression and methylation at the C9orf72 locus, reduced intron retention in the edited lines, and abolished pathological phenotypes associated with theC9orf72HRE expansion in iPSC derived motor neurons (iPSMNs).

RNA sequencing of the mutant line identified 2220 differentially expressed genes compared to its isogenic control. Enrichment analysis demonstrated an over-representation of ALS relevant pathways, including calcium ion dependent exocytosis, synaptic transport and the KEGG ALS pathway, as well as new targets of potential relevance to ALS pathophysiology.

Complete correction of theC9orf72HRE in iPSMNs by CRISPR/Cas9 mediated HDR provides an ideal model to study the earliest effects of the hexanucleotide expansion on cellular homeostasis and the key pathways implicated in ALS pathophysiology.
QuAdTrim: Overcoming computational bottlenecks in sequence quality control
Authors: Robinson Andrew J. , Ross Elizabeth M.
Published: December 2019

With the recent torrent of high throughput sequencing (HTS) data the necessity for highly efficient algorithms for common tasks is paramount. One task for which the basis for all further analysis of HTS data is initial data quality control, that is, the removal or trimming of poor quality reads from the dataset. Here we present QuAdTrim, a quality control and adapter trimming algorithm for HTS data that is up to 57 times faster and uses less than 0.06% of the memory of other commonly used HTS quality control programs. QuAdTrim will reduce the time and memory required for quality control of HTS data, and in doing, will reduce the computational demands of a fundamental step in HTS data analysis. Additionally, QuAdTrim impliments the removal of homopolymer Gs from the 3’ end of sequence reads, a common error generated on the NovaSeq, NextSeq and iSeq100 platforms.

Availability and Implementation

The source code is freely available on bitbucket under a BSD licence, see COPYING file for details:https://bitbucket.org/arobinson/quadtrim

Contact

Andrew Robinson andrewjrobinson at gmail dot com
Flood-pulse disturbances as a threat for long-living Amazonian trees
Authors: Resende Angélica F , Piedade Maria T F , Feitosa Yuri O , Andrade Victor Hugo F , Trumbore Susan E , Durgante Flávia M , Macedo Maíra O , Schöngart Jochen
Published: December 2019

The long-living tree speciesEschweilera tenuifolia(O. Berg) Miers (Lecythidaceae) is characteristic to oligotrophic floodplain forests (igapó) influenced by a regular and predictable flood-pulse. This species preferentially occurs at macrohabitats flooded up to 10 months per year forming monodominant stands. We aimed to analyze the growth and mortality patterns of this species under pristine conditions (Jaú National Park-JNP) and in an impactedigapó(Uatumã Sustainable Development Reserve-USDR) where the downstream flood-pulse disturbance occasioned by the Balbina hydroelectric plant caused massive mortality of this species. Using a total of 91 trees (62 living and 29 dead) at the USDR and 52 (31 living and 21 dead) from JNP, we analyzed age-diameter relationships, mean passage time through 5-cm diameter classes, growth change patterns, growth ratios, clustering of mean diameter increment (MDI), and dated the year of death from each individual using radiocarbon (14C) analysis. Growth and mortality patterns were then related to climatic or anthropogenic disturbances. Our results show similar structural parameters for both studied populations regarding the estimated maximum ages of 466 years (JNP) and 498 years (USDR) and MDI, except for one single tree at the USDR with an estimated age of 820 yrs. Living trees from JNP showed distinctly altered growth after 1975, probably related to consecutive years of high annual minimum water levels. Tree mortality in the JNP occurred during different periods, probably induced by extreme hydroclimatic events. At the USDR changes in growth and mortality patterns occurred after 1983, when the Balbina dam construction started. Despite being one of the best flood-adapted tree species,E. tenuifoliaseems to be sensitive to both, long-lasting dry and wet periods induced by climatic or anthropogenic disturbances or resulting synergies among both. Even more than 30 years after the start of disturbances at the USDR, the flood-pulse alteration continues affecting both mortality and growth of this species which can potentially cause regional extinction.
PUMA: PANDA Using MicroRNA Associations
Authors: Kuijjer Marieke L. , Fagny Maud , Marin Alessandro , Quackenbush John , Glass Kimberly
Published: December 2019

Conventional methods to analyze genomic data do not make use of the interplay between multiple factors, such as between microRNAs (miRNAs) and the mRNA transcripts they regulate, and thereby often fail to identify the cellular processes that are unique to specific tissues. We developed PUMA (PANDA Using MicroRNA Associations), a computational tool that uses message passing to integrate a prior network of miRNA target predictions with protein-protein interaction and target gene co-expression information to model genome-wide gene regulation by miRNAs. We applied PUMA to 38 tissues from the Genotype-Tissue Expression (GTEx) project, integrating RNA-Seq data with two different miRNA target predictions priors, built on predictions from TargetScan and miRanda, respectively. We found that while target predictions obtained from these two different resources are considerably different, PUMA captures similar tissue-specific miRNA-target gene regulatory interactions in the different network models. Furthermore, tissue-specific functions of miRNAs, which we identified by analyzing their regulatory profiles and which we made available through a Shiny app (https://kuijjer.shinyapps.io/puma_gtex/), are highly similar between networks modeled on the two target prediction resources. This indicates that PUMA consistently captures important tissue-specific regulatory processes of miRNAs. In addition, using PUMA we identified miRNAs regulating important tissue-specific processes that, when mutated, may result in disease development in the same tissue. PUMA is available in C++, MATLAB, and Python code on GitHub (https://github.com/kuijjerlab/PUMAandhttps://github.com/kuijjerlab/PyPuma).
Mucin hydrogel glyco-modulation to investigate immune activity of mucin glycans
Authors: Yan Hongji , Hjorth Morgan , Winkeljann Benjamin , Dobryden Illia , Lieleg Oliver , Crouzier Thomas
Published: December 2019

Mucins are multifunctional glycosylated proteins that are increasingly investigated as building blocks of novel biomaterials. Once assembled into hydrogels (Muc gels), mucins were shown to modulate the recruitment and activation of immune cells and avoid fibrous encapsulationin vivo. However, nothing is known about the early immune response to Muc gels. This study characterizes the response of macrophages, important orchestrators of the material-mediated immune response, over the first 7 days in contact with Muc gels. The role of mucin-bound sialic acid sugar residues was investigated by first enzymatically cleaving the sugar, then assembling the mucin variants into covalently crosslinked hydrogels with rheological and surface nanomechanical properties similar to non-modified Muc gels. Results with THP1 and human primary peripheral blood monocytes-derived macrophages were strikingly consistent and showed that Muc gels transiently activate the expression of both pro-inflammatory and anti-inflammatory cytokines and cell surface markers, with a maximum on the first day and loss of the effect after 7 days. The activation was sialic acid-dependent for a majority of the markers followed. The pattern of gene expression, protein expression, and functional measurements did not strictly correspond to M1 or M2 macrophage phenotypes. This study highlights the complex early events in macrophage activation in contact with mucin materials and the importance of sialic acid residues in such a response. The enzymatic glyco-modulation of Muc gels appears as a useful tool to help understand the biological functions of specific glycans on mucins which can further inform on their use in various biomedical applications.
Ignoring correlated activity causes a failure of retinal population codes under moonlight conditions
Authors: Ruda Kiersten , Zylberberg Joel , Field Greg D.
Published: December 2019

The retina encodes visual stimuli across light intensities spanning 10-12 orders of magnitude from starlight to sunlight. To accommodate this enormous range, adaptation alters retinal output, changing both the signal and noise among populations of retinal ganglion cells (RGCs). Here we determine how these light level-dependent changes in signal and noise impact decoding of retinal output. In particular, we consider the importance of accounting for noise correlations among RGCs to optimally read out retinal activity. We find that at moonlight conditions, correlated noise is greater and assuming independent noise severely diminished decoding performance. In fact, assuming independence among a local population of RGCs produced worse decoding than using a single RGC, demonstrating a failure of population codes when correlated noise is substantial and ignored. We generalize these results with a simple model to determine the signal and noise conditions under which this failure of population processing can occur. This work elucidates the circumstances in which accounting for noise correlations is necessary to take advantage of population-level codes and shows that sensory adaptation can strongly impact decoding requirements on downstream brain areas.
Chromatin regulatory dynamics of early human small intestinal development using a directed differentiation model
Authors: Hung Yu-Han , Huang Sha , Dame Michael K. , Yu Qianhui , Yu Qing Cissy , Zeng Yi Arial , Camp J. Gray , Spence Jason R. , Sethupathy Praveen
Published: December 2019

Background

The establishment of the small intestinal (SI) lineage during human embryogenesis is critical for the proper development of neonatal gut functions, including nutrient absorption and immune defense. The chromatin dynamics and regulatory networks that drive human SI lineage formation and regional patterning are essentially unknown. To fill this knowledge void, we apply a cutting-edge genomic technology to a state-of-the-art human model of early SI development. Specifically, we leverage chromatin run-on sequencing (ChRO-seq) to define the landscape of active promoters, enhancers, super enhancers, and gene bodies across distinct stages of directed differentiation of human pluripotent stem cells (hPSCs) into SI spheroids with regional specification.

Results

Through comprehensive ChRO-seq analysis we identify candidate stage-specific chromatin activity states, novel markers, and enhancer hotspots during the directed differentiation process. Moreover, we propose a detailed transcriptional network associated with SI lineage formation or initial regional patterning. Among our findings is a unique pattern of enhancer activity and transcription at HOX gene loci that is previously undescribed. Analysis of single cell RNA-seq data from human fetal SI at early developmental time points shed further light on the unique HOX gene temporal dynamics that underlies SI regional patterning.

Conclusions

Overall, the results lead to a new proposed working model for the regulatory underpinnings of human SI lineage formation and regional patterning, thereby adding a novel dimension to the literature that has thus far relied almost exclusively on non-human models.
Compensatory mutation can drive gene regulatory network evolution
Authors: Wang Yifei , Richards Marios , Dorus Steve , Priest Nicholas K. , Bryson Joanna J.
Published: December 2019

Gene regulatory networks underlie every aspect of life; better understanding their assembly would better our understanding of evolution more generally. For example, evolutionary theory typically assumed that low-fitness intermediary pathways are not a significant factor in evolution, yet there is substantial empirical evidence of compensatory mutation. Here we revise theoretical assumptions to explore the possibility that compensatory mutation may drive rapid evolutionary recovery. Using a well-establishedin silicomodel of gene regulatory networks, we show that assuming only that deleterious mutations are not fatal, compensatory mutation is surprisingly frequent. Further, we find that it entails biases that drive the evolution of regulatory pathways. In our simulations, we find compensatory mutation to be common during periods of relaxed selection, with 8-15% of degraded networks having regulatory function restored by a single randomly-generated additional mutation. Though this process reduces average robustness, proportionally higher robustness is found in networks where compensatory mutations occur close to the deleterious mutation site, or where the compensatory mutation results in a large regulatory effect size. This location- and size-specific robustness systematically biases which networks are purged by selection for network stability, producing emergent changes to the population of regulatory networks. We show that over time, large-effect and co-located mutations accumulate, assuming only that episodes of relaxed selection occur, even very rarely. This accumulation results in an increase in regulatory complexity. Our findings help explain a process by which large-effect mutations structure complex regulatory networks, and may account for the speed and pervasiveness of observed occurrence of compensatory mutation, for example in the context of antibiotic resistance, which we discuss. If sustained byin vitroexperiments, these results promise a significant breakthrough in the understanding of evolutionary and regulatory processes.