bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluoroscopic evaluation of the influence of needle gauge on epidural spread in caudal block
Authors: Sim Woo Seog , Park Hue Jung , Kwon Ji Hye , Oh Min Seok , Jung Hyun Joo , Cho Min Kyoung , Lee Jin Young
Published: May 2019

Caudal block has limited injectate distribution to the desired lumbar level due to the relatively long distance from the injection site and reduction in the volume of injectate due to leakage into the sacral foramen. The objective of this study was to investigate the influence of needle gauge on fluoroscopic epidural spread and to assess the correlation between the spread level and analgesic efficacy in patients undergoing caudal block. We retrospectively analyzed data from 80 patients who received caudal block for lower back and radicular pain. We categorized patients based on the epidural needle gauge used into group A (23 gauge), group B (20 gauge), and group C (17 gauge). Fluoroscopic image of the final level of contrast injected through the caudal needle and pain scores before the block and 30 minutes after the block recorded using a numerical rating scale, were evaluated. Of the 80 patients assessed for eligibility, 7 were excluded. Thus, a total of 73 patients were finally analyzed. Age, sex, body mass index, diagnosis, lesion level, lesion severity, and duration of pain did not differ among the 3 groups. All patients showed cephalic spread of contrast. Contrast spread beyond L5 was seen in 26.9% of patients in group A, 41.7% in group B, 39.1% in group C, and 35.6% overall; there was no significant difference among the groups (P = .517). Analgesic efficacy was not significantly different among the groups (P = .336). The needle gauge did not influence the level of epidural spread or analgesic efficacy in caudal block.
Moderate hypercapnia may not contribute to postoperative delirium in patients undergoing bronchoscopic intervention
Authors: Cheng Qinghao , Li Lei , Yang Mingyuan , Sun Lei , Li Renjiao , Huang Rui , Ma Jun
Published: May 2019

This study aimed to investigate the risk factors and whether acute hypercapnia contributes to postoperative delirium (POD) during bronchoscopic intervention under general anesthesia or deep sedation.

A prospective study was conducted with 119 consecutive patients who had undergone bronchoscopic intervention between February 2016 and December 2016 at the Emergency General Hospital.

Twenty-eight patients (23.8%) were diagnosed with POD. The patients were divided into 2 groups: the POD (n = 28) and the control group (n = 91). The mean age of the POD group was higher than that of the control group (P < .01). All the blood gas values, PaCO2 (P < .01), PaO2 (P < .01), and PH (P < .01), were significantly different. Multivariate analyses revealed that age (P < .01), operation duration (P = .01), and PO2 (P = .01) were independent predictive factors of POD, while hypercapnia (P = .54) was established as not being a predictive factor of POD.

Age, operation duration, and PO2 were determined as independent predictive factors of POD, whereas moderate hypercapnia is not likely to contribute to POD in patients undergoing bronchoscopic intervention. Clinical Trial Registration Identifier: ChiCTR-POC-15007483.
Enhancement of in vitro proliferation and bioactivity of human anterior cruciate ligament fibroblasts using an in situ tissue isolation method and basic fibroblast growth factor culture conditions
Authors: Liu Ziming , Li Yuwan , Ren Youliang , Jin Ying , Yang Jibin , Wang Shengmin , Zhu Xizhong , Xiong Huazhang , Zou Gang , Liu Yi , Huang Wei
Published: May 2019

Background:

Previous studies have reported poor proliferation and bioactivity of human anterior cruciate ligament fibroblasts (hACLFs) after injury. As hACLFs are one of the most significant and indispensable source of seed cells in constructing tissue-engineered ligament, enhancing hACLF proliferation would offer favorable cellular-biological ability and induce the extracellular matrix secretion of hACLFs after loading on multiple types of scaffolds. Enhancing the bioactivity of hACLFs would improve tissue repair and functional recovery after tissue-engineered ligament transplantation. This study compared cells prepared by collagenase digestion and the in situ culture of tissue pieces and investigated the effect of basic fibroblast growth factor (bFGF) on hACLFs.

Methods:

Six adult patients participated in this study. Of these patients, tissues from three were compared after culture establishment through collagenase digestion or in situ tissue isolation. hACLF phenotypic characteristics were assessed, and the effect of bFGF on hACLF cultures was observed. hACLFs cultured with and without bFGF served as the experimental and control groups, respectively. Cell Counting Kit-8 was used to detect proliferation. The expression of ligament-related genes and proteins was evaluated by immunofluorescence staining, real-time polymerase chain reaction (PCR) assays, and Western blot assays.

Results:

The morphology of hACLFs isolated using the two methods differed after the 2nd passage. The proliferation of cells obtained by in situ culture was higher than that of cells obtained by collagenase digestion. hACLFs cultured with bFGF after the 3rd passage exhibited a higher proliferation rate than the controls. Immunofluorescence staining, real-time PCR, and Western blot analysis showed a significant increase in ligament-related gene and protein expression in the hACLFs cultured with bFGF.

Conclusions:

The in situ isolation of tissue pieces enhanced hACLF proliferation in vitro, and the hACLFs exhibited phenotypic characteristics of fibroblasts. hACLFs cultured with bFGF exhibited increased hACLF bioactivity.
Is the extirpative surgery for primary tumor helpful for the patients with metastatic urothelial cancer at the time of diagnosis?
Authors: Kim Jongchan , Park Sung Yul , Elghiaty Ahmed , Jang Won Sik , Heo Ji Eun , Park Jee Soo , Choi Young Deuk , Ham Won Sik
Published: May 2019

The stagnant mortality rates for metastatic urothelial cancer (UC) have provoked efforts to find novel treatments. To test the utility of the extirpative surgery for primary tumor as an option for these patients, we investigated the perioperative and oncologic outcomes of surgery for primary tumors in metastatic UC patients.

We reviewed the medical records of 130 metastatic UC patients (bladder: 88, upper tract UC: 42) at diagnosis from November 2005 to November 2016. A total of 56 patients (surgery group) underwent chemotherapy with extirpative surgery for the primary tumor, and 74 patients (non-surgery group) received chemotherapy. We evaluated perioperative outcomes, cancer-specific survival (CSS), and overall survival (OS) using Kaplan-Meier methods and factors related to OS and CSS using Cox regression models.

Surgery group showed similar perioperative outcome and postoperative complications to those previously reported in UC patients without metastasis, and fewer urinary complications than non-surgery group. Surgery group showed better oncological outcomes than non-surgery group for median CSS (16.0 vs 10.0 months, P = 0.014) and median OS (14.0 vs 9.0 months, P = 0.043). Multivariate analysis showed Eastern Cooperative Oncology Group performance status and metastasis to liver as significant predictors of CSS and OS. Surgery was not related with OS, but a significant predictor of CSS.

Extirpative surgery for primary tumor in metastatic UC can be feasible and it might have survival benefits, especially those patients with a tolerable general condition and no liver metastasis. In addition, LT reduces the possibility of a surgical procedure towing to urinary complications.
Current approaches to cleft lip revision
Authors: Garland Katie , Matic Damir
Published: May 2019

Purpose of review

Cleft lip repair requires multidisciplinary follow-up throughout a child's life and often requires lip revision surgery in adolescence to restore function and symmetry of the lip. There is significant variability in the approaches taken for lip repair and therefore a review of current techniques and subsequent guidance to secondary cleft lip repair is warranted.

Recent findings

New methods of secondary reconstruction can be divided into superficial or muscle related. Recent suggestions for superficial reconstruction include botulinum toxin injection, silicone gel sheeting, local flap reconstruction, fat grafting, and CO2 laser ablation. Suggestions for muscular reconstruction include pedicled prolabial flaps, modified Abbe flap, and orbicularis oris eversion.

Secondary cleft lip deformities can be classified as superficial or muscle related. Superficial problems require relatively minor treatments such as laser, local scar revisions, small local flaps, mucosal excision, or fat grafting. Muscle deformities generally require total lip revision and rerepair as a first step to achieving longstanding improvements in lip esthetics and function. Cleft lip revision should only be considered in concert with the patient, be based on the patient's concerns and desires, and offered at the appropriate timeline to improve social integration and/or psychosocial wellbeing.
Effect of a Systemwide Approach to a Reduction in Central Line–Associated Bloodstream Infections
Authors: Ferrari Sarah , Taylor Kristine
Published: May 2019

Background:

Unit-based initiatives were deployed independently creating silos in practice variability across the system with little impact on reduction of central line–associated bloodstream infections (CLABSI).

Problem:

The goal was to decrease CLABSI systemwide by establishing standardized evidence-based practice (EBP) procedures to advance nursing practice.

Approach:

A new innovative method, the Ferrari Method for Practice Standardization, enhanced the quality infrastructure by merging EBP and lean methodology to translate nursing innovations into practice. Leveraging a culture of shared decision making to support autonomy, as well as collaborating interprofessionally, allowed the organization to standardize and sustain CLABSI prevention.

Outcomes:

The Ferrari Method for Practice Standardization successfully reduced CLABSI rates by 48% over a 1-year improvement cycle. Eight standardized EBP clinical procedures were developed and implemented across the organization.

Conclusion:

The implementation of the Ferrari Method for Practice Standardization swiftly moves new knowledge into clinical practice to improve outcomes. Using standardized improvement methodology, it eases the interprofessional approval processes, maximizes autonomy, and focuses on quality care.
Delivering Leadership Experiences for Master’s-Prepared Clinical Nurses via a Nurse Residency Program
Authors: Kohler Jennifer , Dixon Joanna
Published: May 2019

A new advancement model implemented at a large healthcare organization provided master’s-prepared clinical nurses the opportunity to gain leadership skills through working with a nurse residency program while being mentored by nursing professional development practitioners. The outcomes of resource allocation and growth were valuable for the organization, and master’s-prepared clinical nurses are now contributing towards the nurse residency program’s leadership roles.
Using Virtual Site Visits in the Clinical Evaluation of Nurse Practitioner Students
Authors: Harris Melodee , Rhoads Sarah J. , Rooker Janet S. , Kelly Mary Alice , Lefler Leanne , Lubin Sandra , Martel Isis L. , Beverly Claudia J.
Published: May 2019

Background

The use of telehealth technology to conduct virtual site visits is an innovative strategy for evaluating the performance of nurse practitioner (NP) students in remote settings. Although there is an abundance of studies on telehealth for the remote monitoring and assessment of patients, there are limited data on its use for evaluating NP students during clinical learning experiences.

Purpose

The purpose of this project was to understand the perspectives of NP students and faculty on the feasibility of using virtual site visits to evaluate the students' performance during clinical experiences.

Methods

Online surveys were used to collect student and faculty perspectives on the use of virtual technology during clinical site observations.

Results

Overall, students and faculty reported positive experiences with the virtual site visits.

Conclusion

Virtual site visits are feasible in most clinical settings.
Underreporting of Bloodborne Pathogen Exposures in Nursing Students
Authors: Black Thomas Lisa M.
Published: May 2019

Background

Although nursing students perform many of the same procedures as licensed nurses, students are less skillful when handling sharps and are at higher risk of injury. Low rates of bloodborne pathogen (BBP) exposure reporting are described among students in all health care disciplines.

Purpose

This study describes reporting behaviors of undergraduate nursing students who experienced a needlestick injury during a clinical practicum experience.

Methods

This study implemented a retrospective survey design to query the BBP exposure experience of nursing students in prelicensure nursing programs.

Results

Of the 4140 survey responses, 6.6% (n = 274) of respondents sustained a percutaneous BBP exposure during a clinical practicum experience, and 52% (n = 127) of these exposures were not reported. Reasons for nonreporting included fear the student would “get in trouble,” that the incident would affect the student's clinical grade, and concern about being perceived as lacking clinical skill.

Conclusions

Bridging communication gaps between students and faculty is essential to ensure that students report BBP exposures to permit access to timely triage and exposure management.
Patients' Perceptions of Experiences of Recovering From Acute Pancreatitis
Authors: Boije Karin , Drocic Amra , Engström My , Bjerså Kristofer
Published: May 2019

The incidence of registered admissions in inpatient care with a diagnosis of acute pancreatitis was 58 per 100,000 capita in Sweden during the year 2013. Although acute pancreatitis is a well-explored area, there is a demand for research from the patients' perceptions. The aim of this study was to describe patients' perceptions of recovering from acute pancreatitis. Data collection for this phenomenographical study included 16 individual semistructured interviews. Analysis was done according to the 7 steps suggested by Sjöström and Dahlgren (2002). Recovery after acute pancreatitis was perceived within 5 categories; a time of physical suffering, an emotional journey, challenges to the usual life and its good qualities, barriers and need for social support, and healthcare as an important factor. Physical and emotional symptoms influence recovery after acute pancreatitis by challenging the good things and things that are taken for granted in everyday life. Promoting factors toward good recovery was a proper support from the social network as well as healthcare providers.
Nasogastric Tube Feeding Experiences in Pediatric Oncology Patients and Their Mothers
Authors: Bicakli Derya Hopanci , Sari Hatice Yildirim , Yilmaz Medine , Cetingul Nazan , Kantar Mehmet
Published: May 2019

The aim of this qualitative research study is to reveal children's and their mothers' views and experiences related to nasogastric tube feeding, which is the most frequently performed nutrition delivery method in pediatric oncology. The present study was carried out at an university pediatric oncology inpatient service. A total of three children and 14 mothers participated in the study. The analysis of the data was conducted according to Kolcaba's Comfort Theory. The findings resulting from the content analysis were explained under four main themes: (1) physical: includes the inability to be fed orally, nasogastric tube intervention, comfort because of feeding, medication administration, and satisfaction; (2) psychospiritual: includes anxiety, fear, distorted body image, and compliance; (3) sociocultural: includes conflicts with the child about feeding and advice on feeding via the nasogastric tube to other mothers and children; and (4) environmental: includes unrestricted/freedom of feeding. Gastroenterology professionals can also provide basic counseling and resources to children and mothers about the importance of maintaining an optimal weight and of enteral nutrition.
Impact of Colonoscopy Preparation Video on Boston Bowel Preparation Scale Score
Authors: Ho Loan H. , Montealegre Jane R. , Al-Arabi Safa'a , Jibaja-Weiss Maria L. , Suarez Milena Gould
Published: May 2019

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States and the third most common cancer in men and the second most common cancer among women. Early detection of localized adenocarcinoma and adenomatous polyps helps reduce the mortality related to colon cancer. According to the American Gastroenterological Association, colonoscopy (CSPY) is the gold standard in screening for CRC. To improve the results of screening, the CSPY preparation (prep) needs to be optimal. This study was undertaken to determine whether a supplemental standardized educational video on bowel preparation in the viewer's native language would improve bowel preparation at the time of CSPY. After institutional review board approval, the records of adult patients who presented to the gastroenterology clinic were reviewed. Patients who underwent a CSPY were assigned according to whether they watched a supplemental educational video on CSPY bowel preparation in their native language. This video reflects the same information provided in written and verbal form at the time of CSPY scheduling. Bowel prep was rated by the endoscopist using the Boston Bowel Preparation Scale (BBPS) and quantifies the adequacy of the preprocedure bowel prep. Participant characteristics and BBPS scores were statistically assessed for significant differences. We identified a total of 186 patients, 91 in March 2015 (pre–video intervention) and 95 in March 2016 (post–video intervention). Mean BBPS score was 7.9 and 8.54 for the March 2015 and 2016 group, respectively (p value of .0039). Although there was no statistical difference between the 2 groups with concern to gender and age, the racial makeup and BBPS score were statistically different. Multivariate analysis was performed. There was no interaction between gender or race and year effect to account for any difference in that factors' performance. Thus, it can be implied that there is not a consistent race effect but there is a consistent gender effect with females having higher success rates, regardless of video intervention (p value of .003). After controlling for both gender and race, the year effect is modestly significant (p value of .025), with the post–video subjects having higher prep success rates. A supplemental educational video incorporated into precolonoscopy teaching may provide a standardized method of effectively conveying simple bowel prep instructions in an efficient manner. This study demonstrated that using such a video produced significant results in improving the quality of bowel preparation.
Supplemental oxygen for the management of dyspnea in interstitial lung disease
Authors: Schaeffer Michele R. , Molgat-Seon Yannick , Ryerson Christopher J. , Guenette Jordan A.
Published: May 2019

Purpose of review

This article presents a summary of the evidence relating to supplemental oxygen use for the management of dyspnea in patients with interstitial lung disease (ILD).

Recent findings

In contrast to the majority of the available literature, recent findings suggest that supplemental oxygen can significantly reduce exertional dyspnea in ILD. ILD patients’ need for supplemental oxygen often surpasses the levels that the most commonly used oxygen delivery systems provide. More effective delivery of supplemental oxygen has the potential for greater relief of dyspnea. There is also evidence suggesting that indications for supplemental oxygen may differ in ILD compared with other chronic lung diseases.

Large clinical trials are needed to determine if the reductions in dyspnea with supplemental oxygen observed in the laboratory setting can translate into meaningful benefits in everyday life for patients with ILD. More effective and practical oxygen delivery systems are needed. Future guidelines should consider including recommendations addressing the potential role of supplemental oxygen for mildly hypoxemic patients with ILD as well as recommendations specific to supplemental oxygen use for exercise training in ILD.
Interdisciplinary management of chronic breathlessness
Authors: Reilly Charles C. , Brighton Lisa Jane , Maddocks Matthew
Published: May 2019

Purpose of review

Breathlessness is a common yet complex symptom of advanced disease. Effective management will most likely draw upon the skills of multiple disciplines and professions. This review considers recent advances in the management of chronic breathlessness with regards to interdisciplinary working.

Recent findings

There are growing data on interventions for chronic breathlessness that incorporate psychosocial mechanisms of action, for example, active mind–body treatments; and holistic breathlessness services that exemplify interprofessional working with professionals sharing skills and practice for user benefit. Patients value the personalized, empathetic and understanding tenor of care provided by breathlessness services, above the profession that delivers any intervention. Workforce training, decision support tools and self-management interventions may provide methods to scale-up these services and improve reach, though testing around the clinical effects of these approaches is required.

Chronic breathlessness provides an ideal context within which to realize the benefits of interdisciplinary working. Holistic breathlessness services can commit to a comprehensive approach to initial assessment, as they can subsequently deliver a wide range of interventions suited to needs as they are identified.
Multidimensional measurement of breathlessness: recent advances
Authors: Williams Marie T. , Johnston Kylie N.
Published: May 2019

Purpose of review

Breathlessness is a multidimensional sensation for which a range of instruments exists for children, youth and adults, capable or unable to self-report distress with breathing. This review presents developments and applications of multidimensional assessments of breathlessness.

Recent findings

Excluding unidimensional measures and instruments assessing the impact of breathlessness, at least eight psychometrically robust instruments exist, which comprehensively assess one or more specific domains of the sensation of breathlessness (intensity, sensory quality, affective distress). These instruments have evolved from modest beginnings (describing breathlessness in various patient cohorts) to a growing use as primary or secondary outcomes in observational, clinical, and experimental trials exploring breathlessness mechanisms and intervention effects. For adults and children unable to autonomously communicate breathing discomfort, instruments include combinations of physiological and behavioural markers of distress. Nonverbal (graphic scales) have potential use beyond paediatric applications.

Traditionally, breathlessness has been considered as a ‘black box’ with unidimensional measures reflecting box size (intensity, unpleasantness). Multidimensional instruments reveal the composition of the black box of breathlessness allowing detailed descriptions of an individual's breathlessness experience, quantification of sensory qualities, affective distress, and emotional responses with the potential to capture change over time and treatment effects in each dimension.
Climate change effects on Black Sigatoka disease of banana
Authors: Bebber Daniel P.
Published: May 2019

Climate change has significantly altered species distributions in the wild and has the potential to affect the interactions between pests and diseases and their human, animal and plant hosts. While several studies have projected changes in disease distributions in the future, responses to historical climate change are poorly understood. Such analyses are required to dissect the relative contributions of climate change, host availability and dispersal to the emergence of pests and diseases. Here, we model the influence of climate change on the most damaging disease of a major tropical food plant, Black Sigatoka disease of banana. Black Sigatoka emerged from Asia in the late twentieth Century and has recently completed its invasion of Latin American and Caribbean banana-growing areas. We parametrize an infection model with published experimental data and drive the model with hourly microclimate data from a global climate reanalysis dataset. We define infection risk as the sum of the number of modelled hourly spore cohorts that infect a leaf over a time interval. The model shows that infection risk has increased by a median of 44.2% across banana-growing areas of Latin America and the Caribbean since the 1960s, due to increasing canopy wetness and improving temperature conditions for the pathogen. Thus, while increasing banana production and global trade have probably facilitated Black Sigatoka establishment and spread, climate change has made the region increasingly conducive for plant infection.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’. This issue is linked with the subsequent theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’.
Increased frequency of travel in the presence of cross-immunity may act to decrease the chance of a global pandemic
Authors: Thompson R. N. , Thompson C. P. , Pelerman O. , Gupta S. , Obolski U.
Published: May 2019

The high frequency of modern travel has led to concerns about a devastating pandemic since a lethal pathogen strain could spread worldwide quickly. Many historical pandemics have arisen following pathogen evolution to a more virulent form. However, some pathogen strains invoke immune responses that provide partial cross-immunity against infection with related strains. Here, we consider a mathematical model of successive outbreaks of two strains—a low virulence (LV) strain outbreak followed by a high virulence (HV) strain outbreak. Under these circumstances, we investigate the impacts of varying travel rates and cross-immunity on the probability that a major epidemic of the HV strain occurs, and the size of that outbreak. Frequent travel between subpopulations can lead to widespread immunity to the HV strain, driven by exposure to the LV strain. As a result, major epidemics of the HV strain are less likely, and can potentially be smaller, with more connected subpopulations. Cross-immunity may be a factor contributing to the absence of a global pandemic as severe as the 1918 influenza pandemic in the century since.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’. This issue is linked with the subsequent theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’.
Systematic re-annotation of 191 genes associated with early-onset epilepsy unmasks de novo variants linked to Dravet syndrome in novel SCN1A exons
Authors: Steward Charles A. , Roovers Jolien , Suner Marie-Marthe , Gonzalez Jose M. , Uszczynska-Ratajczak Barbara , Pervouchine Dmitri , Fitzgerald Stephen , Viola Margarida , Stamberger Hannah , Hamdan Fadi F. , Ceulemans Berten , Leroy Patricia , Nava Caroline , Lepine Anne , Tapanari Electra , Keiller Don , Abbs Stephen , Sanchis-Juan Alba , Grozeva Detelina , Rogers Anthony S. , Wright James , Choudhary Jyoti , Diekhans Mark , Guigó Roderic , Petryszak Robert , Minassian Berge A. , Cavalleri Gianpiero , Vitsios Dimitrios , Petrovski Slavé , Harrow Jennifer , Flicek Paul , Raymond F. Lucy , Lench Nicholas J. , De Jonghe Peter , Mudge Jonathan M. , Weckhuysen Sarah , Sisodiya Sanjay M. , Frankish Adam
Published: May 2019

The early infantile epileptic encephalopathies (EIEE) are a group of rare, severe neurodevelopmental disorders, where even the most thorough sequencing studies leave 60-65% of patients without a molecular diagnosis. Here, we explore the incompleteness of transcript models used for exome and genome analysis as one potential explanation for lack of current diagnoses. Therefore, we have updated the GENCODE gene annotation for 191 epilepsy-associated genes, using human brain-derived transcriptomic libraries and other data to build 3,550 novel putative transcript models. The extended transcriptional footprint of these genes allowed for 294 intronic or intergenic variants, found in human mutation databases, to be reclassified as exonic, while a further 70 intronic variants were reclassified as splice-site proximal. Using SCN1A as a case study due to its close phenotype/genotype correlation with Dravet syndrome, we screened 122 people with Dravet syndrome, or a similar phenotype, with a panel of novel exon sequences representing eight established genes and identified two de novo SCN1A variants that now, through improved gene annotation can be ascribed to residing among novel exons. These two (from 122 screened patients, 1.6%) new molecular diagnoses carry significant clinical implications. Furthermore, we identified a previously-classified SCN1A intronic Dravet-associated variant that now lies within a deeply conserved novel exon. Our findings illustrate the potential gains of thorough gene annotation in improving diagnostic yields for genetic disorders. We would expect to find new molecular diagnoses in our 191 genes that were originally suspected by clinicians for patients, with a negative diagnosis.
Mammary mechanobiology: mechanically-activated ion channels in lactation and involution
Authors: Stewart Teneale A. , Hughes Katherine , Stevenson Alexander J. , Marino Natascia , Ju Adler L. , Morehead Michael , Davis Felicity M.
Published: May 2019

A mother’s ability to produce a nutritionally-complete neonatal food source has provided a powerful evolutionary advantage to mammals. Milk production by secretory mammary epithelial cells is adaptive, its release is exquisitely timed and its own glandular stagnation with the permanent cessation of suckling triggers the programmed cell death and tissue remodeling that enables female mammals to nurse successive progeny. Both chemical and mechanical signals control epithelial expansion, function and remodeling. Despite this duality of input, however, the nature and function of mechanical forces in the mammary gland remain unknown. Here, we characterize the mammary force landscape and the capacity of luminal and basal epithelial cells to experience and exert force. We explore the molecular instruments for force-sensing in the mammary gland and the physiological requirement for PIEZO1 in lactation and involution. Our study supports the existence of a multifaceted system of chemical and mechanical sensing in the mammary gland, and a protective redundancy that ensures continued lactational competence and offspring survival.
Dentate gyrus neurons that are born at the peak of development, but not before or after, die in adulthood
Authors: Ciric Tina , Cahill Shaina P. , Snyder Jason S.
Published: May 2019

In the dentate gyrus of the rodent hippocampus, neurogenesis begins prenatally and continues to the end of life. Adult-born neurons often die in the first few weeks after mitosis, but then survive indefinitely. In contrast, neurons born at the peak of development are initially stable but can die later in adulthood. Physiological and pathological changes in hippocampal structure may therefore result from both the addition of new neurons and the loss of older neurons. However, it is unknown whether neurons born at other stages of development also undergo delayed cell death. Here, we used BrdU to label dentate granule cells that were born in rats on embryonic day 19 (E19; before the developmental peak), postnatal day 6 (P6; peak) and P21 (after the peak). We quantified BrdU+ neurons in separate groups of rats at 2 and 6 months post-BrdU injection. Consistent with previous work, there was a 15% loss of P6-born neurons between 2 and 6 months of age. In contrast, E19- or P21-born neurons were stable throughout young adulthood. Delayed death of P6-born neurons suggests they may play a unique role in hippocampal plasticity and pathology in adulthood.
Modeling binary and graded cone cell fate patterning in the mouse retina
Authors: Eldred Kiara C. , Avelis Cameron , Johnston Robert J. , Roberts Elijah
Published: May 2019

Nervous systems are incredibly diverse, with myriad neuronal subtypes defined by gene expression. How binary and graded fate characteristics are patterned across tissues is poorly understood. Expression of opsin photopigments in the cone photoreceptors of the mouse retina provides an excellent model to address this question. Individual cones express S-opsin only, M-opsin, or both S-opsin and M-opsin. These cell populations are patterned along the dorsal-ventral axis, with greater M-opsin expression in the dorsal region and greater S-opsin expression in the ventral region. Thyroid hormone signaling plays a critical role in activating M-opsin and repressing S-opsin. Here, we developed an image analysis approach to identify individual cone cells and evaluate their opsin expression from immunofluorescence imaging tiles spanning roughly 6 mm along the D-V axis of the mouse retina. From analyzing the opsin expression of ∼250,000 cells, we found that cones make a binary decision between S-opsin only and co-expression competent fates. Co-expression competent cells express graded levels of S- and M-opsins, depending nonlinearly on their position in the dorsal-ventral axis. M- and S-opsin expression display differential, inverse patterns. Using these single-cell data we developed a quantitative, stochastic model of cone cell decisions in the retinal tissue based on thyroid hormone signaling activity. The model recovers the probability distribution for cone fate patterning in the mouse retina and describes a minimal set of interactions that are necessary to reproduce the observed cell fates. Our study provides a paradigm describing how differential responses to regulatory inputs generate complex patterns of binary and graded cell fates.

Author Summary

The development of a cell in a mammalian tissue is governed by a complex regulatory network that responds to many input signals to give the cell a distinct identity, a process referred to as cell-fate specification. Some of these cell fates have binary on-or-off gene expression patterns, while others have graded gene expression that changes across the tissue. Differentiation of the photoreceptor cells that sense light in the mouse retina provides a good example of this process. Here, we explore how complex patterns of cell fates are specified in the mouse retina by building a computational model based on analysis of a large number of photoreceptor cells from microscopy images of whole retinas. We use the data and the model to study what exactly it means for a cell to have a binary or graded cell fate and how these cell fates can be distinguished from each other. Our study shows how tens-of-thousands of individual photoreceptor cells can be patterned across a complex tissue by a regulatory network, creating a different outcome depending upon the received inputs.
Impaired Social Learning Predicts Reduced Real-life Motivation in Individuals with Depression: A Computational fMRI Study
Authors: Frey Anna-Lena , McCabe Ciara
Published: May 2019

Background

Major depressive disorder is associated with altered social functioning and impaired learning, on both the behavioural and the neural level. These deficits are likely related, considering that successful social interactions require learning to predict other people’s emotional responses. Yet, there is little research examining this relation.

Methods

Forty-three individuals with high (HD; N=21) and low (LD; N=22) depression scores answered questions regarding their real-life social experiences and performed a social learning task during fMRI scanning. As part of the task, subjects learned associations between name cues and rewarding (happy faces) or aversive (fearful faces) social outcomes. Using computational modelling, behavioural and neural correlates of social learning were examined and related to real-life social experiences.

Results

HD participants reported reduced motivation to engage in real-life social activities and demonstrated elevated uncertainty about social outcomes in the task. Moreover, HD subjects displayed altered encoding of social reward predictions in the insula, temporal lobe and parietal lobe. Interestingly, across all subjects, higher task uncertainty and reduced parietal prediction encoding were associated with decreased motivation to engage in real-life social activities.

Limitations

The size of the included sample was relatively small. The results should thus be regarded as preliminary and replications in larger samples are called for.

Conclusion

Taken together, our findings suggest that reduced learning from social outcomes may impair depressed individuals’ ability to predict other people’s responses in real life, which renders social situations uncertain. This uncertainty, in turn, may contribute to reduced social engagement (motivation) in depression.
De novo transcriptome analysis of dermal tissue from the rough-skinned newt, Taricha granulosa, enables investigation of tetrodotoxin expression
Authors: Glass Haley C. , Melin Amanda D. , Vamosi Steven M.
Published: May 2019

Background

Tetrodotoxin (TTX) is a potent neurotoxin used in anti-predator defense by several aquatic species, including the rough-skinned newt, Taricha granulosa. While several possible biological sources of newt TTX have been investigated, mounting evidence suggests a genetic, endogenous origin. We present here a de novo transcriptome assembly and annotation of dorsal skin samples from the tetrodotoxin-bearing species T. granulosa, to facilitate the study of putative genetic mechanisms of TTX expression.

Findings

Approximately 211 million read pairs were assembled into 245,734 transcripts using the Trinity de novo assembly method. Of the assembled transcripts, we were able to annotate 34% by comparing them to databases of sequences with known functions, suggesting that many transcripts are unique to the rough-skinned newt. Our assembly has near-complete sequence information for an estimated 83% of genes based on Benchmarking Universal Single Copy Orthologs. We also utilized other comparative methods to assess the quality of our assembly. The T. granulosa assembly was compared with that of the Japanese fire-belly newt, Cynops pyrrhogaster, and they were found to share a total of 30,556 orthologous sequences (12.9% gene set).

Conclusions

We provide a reference assembly for Taricha granulosa that will enable downstream differential expression and comparative transcriptomics analyses. This publicly available transcriptome assembly and annotation dataset will facilitate the investigation of a wide range of questions concerning amphibian adaptive radiation, and the elucidation of mechanisms of tetrodotoxin defense in Taricha granulosa and other TTX-bearing species.
mPFC Spindle Cycles Organize Sparse Thalamic Activation and Recently Active CA1 cells During non-REM Sleep
Authors: Varela C , Wilson MA
Published: May 2019

Sleep oscillations in neocortex and hippocampus are critical for the integration of new episodic memories into stable generalized representations in neocortex. However, the role of the thalamus in this process is poorly understood.

To determine the thalamic contribution to non-REM oscillations (sharp-wave ripples, SWRs; slow/delta; spindles), we recorded units and local field potentials (LFPs) simultaneously in the limbic thalamus, mPFC, and CA1 in rats. We report that the cycles of neocortical spindles provide a key temporal window that coordinates CA1 SWRs with sparse but consistent activation of thalamic units. Thalamic units were phase-locked to delta and spindles in mPFC, and fired at consistent lags with other thalamic units within spindles, while CA1 units that were active during spatial exploration were engaged in SWR-coupled spindles after behavior. The sparse thalamic firing could promote an incremental integration of recently acquired memory traces into neocortical schemas through the interleaved activation of thalamocortical cells.
PyBSASeq: a novel, simple, and effective algorithm for BSA-Seq data analysis
Authors: Zhang Jianbo , Panthee Dilip R.
Published: May 2019

Bulked segregant analysis (BSA), coupled with next generation sequencing (NGS), allows the rapid identification of both qualitative and quantitative trait loci (QTL), and this technique is referred to as BSA-Seq here. The current SNP index method and G-statistic method for BSA-Seq data analysis require relatively high sequencing coverage to detect major single nucleotide polymorphism (SNP)-trait associations, which leads to high sequencing cost. Here we developed a simple and effective algorithm for BSA-Seq data analysis and implemented it in Python, the program was named PyBSASeq. Using PyBSASeq, the likely trait-associated SNPs (ltaSNPs) were identified via Fisher’s exact test and then the ratio of the ltaSNPs to total SNPs in a chromosomal interval was used to identify the genomic regions that condition the trait of interest. The results obtained this way are similar to those generated by the current methods, but with more than five times higher sensitivity, which can reduce the sequencing cost by ~80% and makes BSA-Seq more applicable for the species with a large genome.

Significance Statement

BSA-Seq can be utilized to rapidly identify DNA polymorphismtrait associations, and PyBSASeq allows the detection of such associations at much lower sequencing coverage than the current methods, leading to lower sequencing cost and making BSA-Seq more accessible to the research community and more applicable to the species with a large genome.
OPTIMOS PRIME: An R package for autoecological (optima and tolerance range) data calculation
Authors: Sathicq María Belén , Nicolosi Gelis María Mercedes , Cochero Joaquín
Published: May 2019

Calculation of autoecological data, such as optima and tolerance ranges to environmental variables, can be useful to establish the distribution and abundance of the species. These calculations, although mathematically not complex, can be prone to error when using a large database.

We present an R package (“optimos.prime”) that uses species’ abundance data and environmental data to calculate the optimum value and tolerance range of each species to each environmental factor, by weighted average. Additionally, the package can create caterpillar plots to show the results.

Using sample data from a phytoplankton database, we exemplify the use of the R package and its functions. A stand-alone version for Windows is also provided, and source code and documents are freely available on GitHub to encourage collaborative work.
An Accurate Bioinformatics Tool For Anti-Cancer Peptide Generation Through Deep Learning Omics
Authors: Kaushik Aman Chandra , Li Mengyang , Wei Dong-Qing
Published: May 2019

The Anti-cancer targets play crucial role in signalling processes of cells. We have developed an Anti-Cancer Scanner (ACS) tool for identification of Anti-cancer targets in form of peptides. ACS tool also allows fast fingerprinting of the Anti-cancer targets of significance in the current bioinformatics research. There are tools currently available which predicts the above-mentioned features in single platform. In the present work, we have compared the features predicted by ACS with other on-line available methods and evaluated the performance of the ACS tool. ACS scanned the Anti-cancer target protein sequences provided by the user against the Anti-cancer target data-sets. It has been developed in PERL language and it is scalable having an extensible application in bioinformatics with robust coding architecture. It achieves a prediction accuracy of 95%, which is much higher than the existing tools.
Nuclear actin regulates inducible transcription by enhancing RNA polymerase II clustering
Authors: Wei Mian , Fan Xiaoying , Ding Miao , Li Ruifeng , Shao Shipeng , Hou Yingping , Meng Shaoshuai , Tang Fuchou , Li Cheng , Sun Yujie
Published: May 2019

Gene expression in response to external stimuli underlies a variety of fundamental cellular processes. However, how the transcription machinery is regulated under these scenarios is largely unknown. Here, we discover a novel role of nuclear actin in inducible transcriptional regulation using next-generation transcriptome sequencing and super-resolution microscopy. The RNA-seq data reveal that nuclear actin is required for the establishment of the serum-induced transcriptional program. Using super-resolution imaging, we found a remarkable enhancement of RNA polymerase II (Pol II) clustering upon serum stimulation and this enhancement requires the presence of nuclear actin. To study the molecular mechanisms, we firstly observed that Pol II clusters co-localized with the serum-response genes and nuclear actin polymerized in adjacent to Pol II clusters upon serum stimulation. Furthermore, N-WASP and Arp2/3 are reported to interact with Pol II, and we demonstrated N-WASP is required for serum-enhanced Pol II clustering. Importantly, using an optogenetic tool, we revealed that N-WASP phase-separated with the carboxy-terminal domain of Pol II and nuclear actin. In addition to serum stimulation, we found nuclear actin also essential in enhancing Pol II clustering upon interferon-γ treatment. Taken together, our work unveils nuclear actin promotes the formation of transcription factory on inducible genes, acting as a general mechanism underlying the rapid response to environmental cues.
CLADES: a programmable sequence of reporters for lineage analysis
Authors: Garcia-Marques Jorge , Yang Ching-Po , Espinosa-Medina Isabel , Koyama Minoru , Lee Tzumin
Published: May 2019

We present CLADES (Cell Lineage Access Driven by an Edition Sequence), a technology for cell lineage studies based on CRISPR/Cas9. CLADES relies on a system of genetic switches to activate and inactivate reporter genes in a pre-determined order. Targeting CLADES to progenitor cells allows the progeny to inherit a sequential cascade of reporters, coupling birth order with reporter expression. This gives us temporal resolution of lineage development that can be used to deconstruct an extended cell lineage by tracking the reporters expressed in the progeny. When targeted to the germ line, the same cascade progresses across animal generations, marking each generation with the corresponding combination of reporters. CLADES thus offers an innovative strategy for making programmable cascades of genes that can be used for genetic manipulation or to record serial biological events.

One Sentence Summary

A sequence of reporters for lineage analysis