bluuebunny/crossref_metadata_2025 huggingface dataset:
1542 An Audit of Rates of Lynch Testing in Confirmed Colorectal Cancer Cases
Authors: Cribb E , Liccardo F , Crisford S , Pawa N
Published: October 2021

Introduction

12% of cancers in the UK are colorectal in origin1 with 1-3% secondary to genetic mismatch repair due to Lynch syndrome2, for which the 2017 NICE guidance recommended that patients with colorectal cancer (CRC) be tested3. It increases the risk of developing other cancers such as endometrial, ovarian and small bowel1, changes the oncological treatment offered to CRC patients4,5, and prompts investigation of their relatives for the condition. In this audit we assessed our rates of trust wide Lynch testing.

Method

Patients with a diagnosis of CRC from 2017-2019 were identified from records held by our cancer services department. Histology results were obtained from an online results portal.

Results

345 were included in the analysis, 79% of which were tested for Lynch, with time taken from biopsy to results ranging from 2 to 276 days (average 45). 54% had results within 30 days, 34% between 30 and 90 days and 12% exceeded 90 days. There was no significant difference of Lynch testing rates between each year. The proportion of results returned within 30 days increased by year, with rates of 30% (2017), 55% (2018) and 71% (2019). The median days from biopsy to results also improved, from 39 to 28 and 16 days, respectively.

Conclusions

Rates and efficiency of our screening for lynch syndrome need improvement to meet the target suggested by NICE. The impact of the recent centralisation our regions pathology department on Lynch testing service provision requires further investigation.
1321 Repeat Colonoscopy: Incidence, Etiology, And Suggestions for Improvement
Authors: Bhatti K , Yousef H , Aung M
Published: October 2021

Aim

Colonoscopy is an invasive procedure. Repeating such a procedure has many implications in terms of risks, costs, increased workload and strains on hospital resources. The current study reports the incidence and aetiology of repeat colonoscopies and provides recommendations for improvement.

Method

The current study was conducted at North Cumbria Integrated Care (NCIC) hospitals over a period of 1 year (January 1st to December 31st, 2019). All patients with a label of “Repeat” by JAG software system, were included in the primary analysis. Patients with colonoscopy after 52 weeks of the index procedure, were excluded. Two authors manually assessed the validity of the data and determined “True repeat rate” and aetiology.

Results

During the study period, 4717 colonoscopies were performed, where 187 were recorded as a repeat. Manual validation showed that true repeat cases were 355/4717 (7.52%). Moreover, 5% of the system labelled cases where not true repeats rather were escalated from sigmoidoscopy to colonoscopy. Analysis of the first 1000 colonoscopies detected 72 cases. Male to female ratio was 47:25 with a mean age of 66.26 ± 11.75(SD). The causes included further management of polyps (n = 30); poor bowel preparation(n = 22); inability to proceed (n = 9); anticoagulation (n = 8) and others (n = 3). Subgroup analyses of the polyp group showed that the reasons for repeating colonoscopy in such cases were appropriate.

Conclusions

An operational definition of the ‘Repeat coloscopy’ should be clearly established. Although most of the repeat colonoscopies for “further management of polyps” are appropriate, repeat due to poor bowel preparation and anticoagulation are clearly preventable.
1579 Effect of COVID-19 pandemic on the Suspected Colorectal Cancer Pathway at a District General Hospital
Authors: Connolly T , Nicoll J , Hall C
Published: October 2021

Aim

During the initial phase of the COVID-19 pandemic the British Society of Gastroenterology and Joint Advisory Group on GI Endoscopy published guidance to halt all non-emergency endoscopy. As a result, CT was used as the first-line investigation with delayed completion endoscopy. We reviewed the efficacy of this change to determine its influence on future practice.

Method

All patients referred via the suspected colorectal cancer pathway (SCCP) to our district general hospital from 15/04/20-15/05/20 (during the initial COVID-19 lockdown) were included. Retrospective analysis of patient electronic records, radiology and endoscopy was performed. Results were analysed using χ² statistic. Significant incidental pathology was defined as non-colorectal pathology requiring referral to different speciality or further imaging.

Results

115 patients were included for analysis, mean age 68 years. 2/115 (1.7%) were found to have a colorectal malignancy on CT, with no further diagnoses following completion colonoscopy. CT imaging detected significant incidental pathology in 31/115 (27%). Subgroup analysis by presenting complaint showed significant pathology was most likely to be detected in those presenting with weight loss (13/36, 36.1%, p = 0.049) or anaemia (12/31, 38.7% p = 0.084).

Conclusions

CT is a valuable first-line investigation in SCCP patients. In this cohort, no colorectal malignancies were missed on CT that were later detected on endoscopy and 27% of scans detected significant non-colorectal incidental pathology. Weight loss was found to have a statistically significant correlation with incidental pathology. These findings suggest CT as a possible first-line investigation in patients presenting with weight loss, anaemia or in the event of delayed access to endoscopy.
Love and Imitation: Facial Mimicry and Relationship Satisfaction in Younger and Older Couples
Authors: Rohr Margund K , Salazar Kämpf Maike , Kunzmann Ute
Published: October 2021

Objectives

Social mimicry, the imitation of one’s conversation partner, is associated with empathy, liking, and affiliation. Because previous research has mainly focused on young adulthood and zero acquaintances, little is known about age differences in mimicry and its role in romantic relationships.

Methods

In this study, 37 younger and 41 older couples talked about an ongoing problem faced by one of the partners while being video-recorded. Three independent observers assessed partners’ facial mimicry. After the conversation, couples evaluated the quality of their relationship.

Results

Younger couples imitated each other more than older couples. The link between mimicry and relationship quality was mixed. While facial mimicry was not linked to subjective closeness in either younger or older couples, there was a significant positive association between mimicry and relationship satisfaction in young, but not older, couples.

Discussion

Overall, the results suggest that facial mimicry is a social process that becomes less prevalent and might differ in their function as individuals age.
PSIII-24 Poor gestational nutrition impacts sheep offspring growth but not feed efficiency
Authors: Tillquist Nicole M , Reiter Amanda S , Kawaida Mia Y , Smith Brandon I , Reed Sarah A , Zinn Steven A , Govoni Kristen E
Published: October 2021

The objective was to determine the effects of poor maternal nutrition during gestation on growth and feed efficiency of offspring. We hypothesized that body weights (BW) would decrease and residual feed intake (RFI) would increase (reduced feed efficiency) in offspring of restricted- and over-fed ewes. Forty-six multiparous Dorset ewes pregnant with twins were fed 100%, 60% or 140% of NRC requirements from d 30 of gestation until parturition. Offspring are referred to as CON (n = 10 ewes; 12 rams), RES (n = 13 ewes; 21 rams), and OVER (n = 16 ewes; 13 rams), respectively. Lamb BW were measured weekly from birth to d 28 and biweekly until d 252 of age. Starting at d 167±13.6, daily intake of a complete pelleted feed was recorded using a Super SmartFeed (C-lock Inc., Rapid City, SD) over a 77 d- feeding period. Average BW were taken two days before, at mid-point, and two days after the feeding trial period and RFI was calculated for each animal. Rams were euthanized at d 284±12 and body morphometrics, loin eye area (LEA), back fat thickness, and organ weights were collected. From birth to d 252, ram lambs were 5.4 kg heavier (P < 0.001) than ewe lambs. Control ewe lambs were 4.3 kg heavier than RES and OVER (P < 0.05) from birth to 9 months and CON rams were 4.7 kg heavier (P < 0.01) than RES. Rams (-0.17) were more efficient than ewes (0.23; P < 0.01); however, no dietary treatment difference was observed (P ≥ 0.57). No differences in muscle mass, LEA, and adipose deposition were observed (P ≥ 0.41). These data indicate that poor maternal diet during gestation impacts offspring growth but not RFI. Further investigation is warranted to determine if differences in BW are a result of metabolic alterations impacted by poor maternal nutrition during gestation.
PSII-4 Effect of increased ruminal propionate on the expression of hepatic gluconeogenic genes in cattle on a finishing ration
Authors: McConnell Hunter L , Rathert Abigail R , Foote Andrew P
Published: October 2021

The objective of this experiment was to ascertain if supplementing calcium propionate (CaP) in varying amounts would result in the increased expression of genes related to glucose metabolism in the liver. The study utilized cannulated Holstein steers (n = 6) in a 3 × 6 Latin rectangle with three 15-d periods. The treatments were as follows: Control (no CaP), low propionate (100 g/d CaP), and high propionate (300 g/d CaP). The treatments were administered in halves twice a day through rumen cannulas. The steers were provided with ad libitum finishing ration, using Insentec feeders to record feed intake and unrestricted access to water. Liver biopsies were taken on d15 of each period, a day after a glucose tolerance test, and flash frozen. RNA was extracted from the liver tissue, reverse transcribed for cDNA, and analyzed through quantitative real-time PCR. Five target genes involved in gluconeogenesis were analyzed and included solute carrier family 16 member 1 (SLC16A1), phosphoenolpyruvate carboxykinase 1 (PCK1), phosphoenolpyruvate carboxykinase 2 (PCK2), glucose-6-phosphatase (G6PC), and solute carrier family 2 member 2 (SLC2A2). Data were analyzed using a mixed model with treatment, period, and their interaction included as fixed effects and steer as a random effect. There was no treatment effect on hepatic gene expression (P ≥ 0.57). SLC16A1 showed a negative, correlation with d7 plasma lactate concentration (r = -0.84, P < 0.001) and a negative relationship with fasting plasma lactate concentration (r = -0.55, P = 0.028). SLC2A2 tended to show a positive correlation with fasting plasma glucose (r = 0.44, P = 0.09), fasting plasma lactate concentration (r = 0.43, P = 0.09), and glucose area under the curve (r = 0.46, P = 0.07). These data indicate that increased propionate may not have an impact on hepatic gene expression.
Trabectedin for recurrent WHO grade 2 or 3 meningioma: A randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG)
Authors: Preusser Matthias , Silvani Antonio , Le Rhun Emilie , Soffietti Riccardo , Lombardi Giuseppe , Sepulveda Juan Manuel , Brandal Petter , Brazil Lucy , Bonneville-Levard Alice , Lorgis Veronique , Vauleon Elodie , Bromberg Jacoline , Erridge Sara , Cameron Alison , Lefranc Florence , Clement Paul M , Dumont Sarah , Sanson Marc , Bronnimann Charlotte , Balaná Carmen , Thon Niklas , Lewis Joanne , Mair Maximilian J , Sievers Philipp , Furtner Julia , Pichler Josef , Bruna Jordi , Ducray Francois , Reijneveld Jaap C , Mawrin Christian , Bendszus Martin , Marosi Christine , Golfinopoulos Vassilis , Coens Corneel , Gorlia Thierry , Weller Michael , Sahm Felix , Wick Wolfgang
Published: October 2021

Background

No systemic treatment has been established for meningioma progressing after local therapies.

Methods

This randomized, multicenter, open-label, phase II study included adult patients with recurrent WHO grade 2 or 3 meningioma. Patients were 2:1 randomly assigned to intravenous trabectedin (1.5 mg/m2 every 3 weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). Secondary endpoints comprised overall survival (OS), objective radiological response, safety, quality of life (QoL) assessment using the QLQ-C30 and QLQ-BN20 questionnaires, and we performed tissue-based exploratory molecular analyses.

Results

Ninety patients were randomized (n = 29 in LOC, n = 61 in trabectedin arm). With 71 events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] = 1.42; 80% CI, 1.00-2.03; P = .294) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) and 21.1% (95% CI, 11.3%-32.9%), respectively. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR = 0.98; 95% CI, 0.54-1.76; P = .94). Grade ≥3 adverse events occurred in 44.4% of patients in the LOC and 59% of patients in the trabectedin arm. Enrolled patients had impeded global QoL and overall functionality and high fatigue before initiation of systemic therapy. DNA methylation class, performance status, presence of a relevant co-morbidity, steroid use, and right hemisphere involvement at baseline were independently associated with OS.

Conclusions

Trabectedin did not improve PFS and OS and was associated with higher toxicity than LOC treatment in patients with non-benign meningioma. Tumor DNA methylation class is an independent prognostic factor for OS.
Continued Low Rates of Hepatitis C Virus (HCV) Recurrence in HCV/HIV- and HCV-Infected Participants Who Achieved Sustained Virologic Response After Direct-Acting Antiviral Treatment: Final Results From the AIDS Clinical Trials Group A5320 Viral Hepatitis C Infection Long-term Cohort Study (V-HICS)
Authors: Wyles David L , Kang Minhee , Matining Roy M , Murphy Robert L , Peters Marion G
Published: October 2021

Final results from the long-term Viral Hepatitis C Infection Long-term Cohort Study (V-HICS) found low rates of hepatitis C virus (HCV) recurrence after direct-acting antiviral therapy in both HCV/human immunodeficiency virus (HIV)–coinfected (0.67/100 person-years) and HCV-infected (0.2/100 person-years) groups with >500 person-years of follow-up. Confirmed reinfections were in participants with HIV who reported high-risk behaviors.
Two Types of Formalism of the Rule of Law
Authors: Nishigai Konatsu
Published: October 2021

The aims of this article are twofold: (i) to propose an explanatory framework, focusing on law-making acts, for accounting for whether the formal requirements of the rule of law are fulfilled; and (ii) to propose two further models within this framework. One model, which I call ‘rulebook formalism’, pertains to Parliament’s law-making acts; another model, which I call ‘rights formalism’, concerns the courts’ law-making acts. This distinction results from the different modality of law, ie the different natures of law-making acts. Drawing on speech act theory, I give a general account of the formal requirements as the success conditions of law-making acts. Then, applying this framework, I discuss the formal requirements for Parliament’s law-making acts and the courts’ law-making acts respectively.
Émile Durkheim’s Germany
Authors: Feuerhahn Wolf
Published: October 2021

The importance of German science for Durkheim seems indubitable. But writing about his relationship with Germany is not easy because this very relationship became the main reason for attacks against Durkheim. Indeed, in 1905, Simon Deploige, a Belgian professor at Louvain University, accused him of having imported German science into France without acknowledging that it was “German.” In the tense political international context of the time, the accusation had potentially important consequences because Durkheim, as a Jew, and shortly after the Dreyfus Affair, was eventually accused to be a German spy. How should historians deal with the topic? Saying that Durkheim was “influenced” by German thought may be adopting the point of view of an actor of the time (namely, Deploige). That is why this chapter will not talk about “influence,” a term which suggests that knowledge is received passively. Instead, the chapter focuses on what Durkheim describes as “German” in order to understand how this perception evolved between the 1880s and World War I.
Durkheim, Tarde, Latour
Authors: Schiermer Bjørn
Published: October 2021

This chapter is motivated by the recent reappraisal of the historical debate between Gabriel Tarde and Durkheim. The current interest in this debate is sparked by French actor-network theorist Bruno Latour’s attempt to repatriate Tarde, at the expense of Durkheim, as the true “classic” of (French) sociology. This chapter investigates the central issues to the historical debate, and it discusses Latour’s recent appropriation of it, his interpretation of Tarde, and his critique of Durkheim. First, the author delves into the young Durkheim’s programmatic ideas for his new science of sociology and seeks to make Tarde’s (and Latours) objections understandable. It is demonstrated, however, that while it is true that the young Durkheim was ardently critical toward the concept of imitation, it stands, rather surprisingly, at the very center of his late sociology of religion. Second, the author discusses some main ambivalences in Tarde’s work of great significance for the debate. Third, the author delves into Latour’s critique of Durkheim, assesses the merits of this critique, and intimates a possible compromise between Latour and Durkheim.
The Origins of Temporal Legitimacy
Authors: Campos Andre Santos
Published: October 2021

Historical analyses of the relations between political theory and time often hinge on two claims. The first is that political theorists have until recently put less emphasis on the future than the past when debating political legitimacy and obligation. The second is that the history of political theory draws a fundamental distinction between theories that invoke time to legitimate political structures and theories that reject temporal considerations in favor of timeless principles. This chapter disputes these two claims by maintaining that competing languages of legitimacy harbor different and interrelated conceptions of temporality. A survey of time conceptions in the history of political philosophy shows that normative political theory is inherently multitemporal, involving double regard for the past and the future. And, since even tenseless principles of legitimacy often depend on temporally related forms of formulation and application, considerations about time seem inescapable in normative political theory.
Authorship in the Age of Machine Learning and Artificial Intelligence
Authors: Deltorn J.-M. , Macrez Franck
Published: October 2021

A new generation of machine learning (ML) and artificial intelligence (AI) creative tools are now at the disposal of musicians, professionals and amateurs alike. These new technical intermediaries allow the production of unprecedented forms of compositions, from generating new works by mimicking a style or by mixing a curated ensemble of musical works to letting an algorithm complete one’s own creation in unexpected directions or by letting an artist interact with the parameters of a neural network to explore fresh musical avenues. Unsurprisingly, this new spectrum of algorithmic compositions question both the nature and the degree of involvement of the creator in the musical work. As a consequence, the issue of authorship and, in particular, the assessment of the specific contribution of a (human) creator through the algorithmic pipeline may require special scrutiny when AI and ML tools are used to produce musical works.
Music Theory and Mainstream Digital Journalism
Authors: Barna Alyssa
Published: October 2021

The tools of music theory and analysis have appeared in articles published in popular press venues for the last decade. Many of these articles, however, are written by non-experts and often stir controversy among academic writers due to assumptions or inaccuracies. Instead of passively arguing about this form of public music theory, this chapter encourages academic theorists to write stories for digital journalism outlets by explaining the role and context of this type of journalism, then outlining the process of pitching, writing, and editing a story. This chapter closes with a discussion of the specific responsibilities of music theorists who write for these venues, and the role of the academic in digital journalism.
Contests in Context
Authors: Hrychuk Kontokosta Anne
Published: October 2021

Inscriptions, dating mostly to the second and third centuries ce, and graffiti offer first-hand perspectives on the lives of gladiators and the organization of Roman spectacles. Examples from throughout the Roman world elucidate how inscribed evidence can fundamentally alter our understanding of gladiatorial contests, related monuments, and key actors. This article focuses on a range of inscriptions associated with distinct groups who were involved in Roman gladiatorial competitions and discusses the types of data that can be acquired from each. Inscribed public and tomb monuments as well as extant edicta demonstrate the contributions of elite sponsors and their role in the patronage of the games. Stelae dedicated by gladiatorial familiae celebrate individual gladiators, their training, and successes over worthy opponents. Epigraphs on tombstones hint at the social realities and daily challenges of gladiators. Graffiti offers multivariate viewpoints on the lived experience of performers and audiences from all social ranks.
Depression hurts
Authors: Jackson Hope
Published: October 2021

Depression in African American women is often persistent and severe. Learn how to recognize the causes and build a nurse-patient relationship to provide a safe space.
A nurse is a gift to older parents with COVID-19
Authors: Almahmoud Omar H.
Published: October 2021

Read about how a son, who's also a nurse, cared for his mother after she was infected with COVID-19 and the universal lessons they learned.
Dermoscopic Features of Basal Cell Carcinoma and Their Association with Histological Types in A Chinese Population: A Perspective Study
Authors: Wang Shi-Qi , Liu Jie , Qu Tao , Fang Kai , Jin Hong-Zhong
Published: October 2021

Objective:

The treatments and prognoses of high-risk and low-risk basal cell carcinomas are quite different. This study aimed to examine the dermoscopic features of basal cell carcinomas and assess the association between the features and basal cell carcinomas recurrence risks in a Chinese population.

Methods:

Patients with histopathologically confirmed basal cell carcinomas examined from March 2016 to April 2020 were enrolled. The dermoscopic features were evaluated, and the correlations between these features and the histological types and recurrence risks were assessed.

Results:

The study cohort comprised 119 Chinese patients with a total of 119 skin lesions. The most common dermoscopic feature of basal cell carcinomas was the absence of a pigment network (119/119, 100%), followed by shiny white streaks (105/119, 88.24%), blue-gray ovoid nests (99/119, 83.19%), multiple blue globules (78/119, 65.55%), and arborizing vessels (78/119, 65.55%); yellow-white structures were present in 29/119 lesions (24.37%). Leaf-like and spoke-wheel areas were significantly associated with superficial basal cell carcinomas (P < 0.001), while arborizing vessels (P < 0.001), blue-gray ovoid nests (P < 0.001), and ulceration (P < 0.05) were significantly associated with nonsuperficial basal cell carcinomas subtypes. The dermoscopic features of the high-risk and low-risk groups exhibited considerable overlap; however, the respective independent predictive factors for a high and low risk of basal cell carcinomas recurrence were short fine telangiectases (P < 0.05) and blue-gray ovoid nests (P < 0.05).

Conclusion:

Dermoscopy provides important information about basal cell carcinomas and is helpful in differentiating superficial basal cell carcinomas from other subtypes. The dermoscopic vascular structures and blue-gray ovoid nests play a crucial role in evaluating the basal cell carcinomas risks preoperatively.
The impact of the gut microbiome on liver transplantation
Authors: Duong Nikki , Bajaj Jasmohan Singh
Published: October 2021

Purpose of review

Although gut dysbiosis can hasten disease progression in end-stage liver disease and contribute to disease severity, morbidity and mortality, its impact during and after transplant needs further study.

Recent findings

Changes in the microbiome are associated with hepatic decompensation. Immune homeostasis is further disrupted during transplant and with immunosuppressants required after transplant. There is increasing evidence of the role of microbiota in peri and posttransplant complications.

Although transplant is highly successful with acceptable survival rates, infections, rejection, disease recurrence and death remain important complications. Prognostication and interventions involving the gut microbiome could be beneficial.
Circulating Immunological Biomarkers
Authors: van der Sijde Fleur , Mustafa Dana A.M. , Vietsch Eveline E. , Katsikis Peter D. , van Eijck Casper H. J.
Published: October 2021

To date, little advances have been made toward new and more effective therapies for pancreatic ductal adenocarcinoma (PDAC). Discovery of prognostic and predictive biomarkers is needed to stratify patients for available treatments and to elucidate how new therapies could be developed. Recent studies have made clear that the immune system is not only affected in the microenvironment of the primary tumor and it is also systemically disrupted in PDAC patients. Under normal circumstances, the immune system is in perfect balance with both proinflammatory and anti-inflammatory components present. In this review, we focus on circulating immunological characteristics including immune cells and their subtypes, cytokines, and immune checkpoints in the peripheral blood not only to understand the poor prognosis of PDAC patients but also to find new leads for new innovative therapies.
Caregiver Preferences for Three-Dimensional Printed or Augmented Reality Craniosynostosis Skull Models: A Cross-Sectional Survey
Authors: Chen Jonlin , Kumar Sahana , Shallal Christopher , Leo Kirby T. , Girard Alisa , Bai Yunong , Li Yukang , Jackson Eric M. , Cohen Alan R. , Yang Robin
Published: October 2021

Background:

Recent advances in three-dimensional (3D) printing and augmented reality (AR) have expanded anatomical modeling possibilities for caregiver craniosynostosis education. The purpose of this study is to characterize caregiver preferences regarding these visual models and determine the impact of these models on caregiver understanding of craniosynostosis.

Methods:

The authors constructed 3D-printed and AR craniosynostosis models, which were randomly presented in a cross-sectional survey. Caregivers rated each model's utility in learning about craniosynostosis, learning about skull anatomy, viewing an abnormal head shape, easing anxiety, and increasing trust in the surgeon in comparison to a two-dimensional (2D) diagram. Furthermore, caregivers were asked to identify the fused suture on each model and indicate their preference for generic versus patient-specific models.

Results:

A total of 412 craniosynostosis caregivers completed the survey (mean age 33 years, 56% Caucasian, 51% male). Caregivers preferred interactive, patient-specific 3D-printed or AR models over 2D diagrams (mean score difference 3D-printed to 2D: 0.16,P < 0.05; mean score difference AR to 2D: 0.17,P < 0.01) for learning about craniosynostosis, with no significant difference in preference between 3D-printed and AR models. Caregiver detection accuracy of the fused suture on the sagittal model was 19% higher with the 3D-printed model than with the AR model (P < 0.05) and 17% higher with the 3D-printed model than with the 2D diagram (P < 0.05).

Conclusions:

Our findings indicate that craniosynostosis caregivers prefer 3D-printed or AR models over 2D diagrams in learning about craniosynostosis. Future craniosynostosis skull models with increased user interactivity and patient-specific components can better suit caregiver preferences.
Dermoid Cyst of Nasal Tip and Nasal Septum
Authors: Zhao He , Cao Zhiwei , Gu Zhaowei
Published: October 2021

Dermoid cyst is a congenital and benign disease with most occur on the head and neck. It is rarely that occur on the nasal tip and nasal septum at same time and rarely repair of using nasal septum mucosa. The authors treated a child with dermoid cyst in the nasal tip and septum. Only the dermoid cyst at the tip of the nose caused the change of appearance. Dermoid cyst of nasal septum did not cause any clinical symptoms. She underwent excision of the dermoid cyst at the tip of the nose and endoscopic surgery for the dermoid cyst in the nasal septum and used the nasal septum mucosa for repair at the same time. After 6 months of recovery, the appearance of the nasal tip recovered well without obvious scar, the nasal septum area recovered well, and the local stoma was unobstructed without recurrence. The authors found that this kind of nasal septal cyst with no clinical symptoms can achieve good therapeutic effect through endoscopic surgery and repair of using nasal septum mucosa, with less damage, rapid recovery, and good prognosis.
Pediatric Cranial Defects: What Size Warrants Repair?
Authors: Lane Jaina C. , Black Jonathan S.
Published: October 2021

Purpose:

Identifying which cranial defects among children warrant surgical repair is integral to providing adequate protection of the skull whereas minimizing exposure to surgical complications. This review examines the available evidence regarding the role of defect size in determining the appropriateness of nonsurgical versus surgical management.

Methods:

An electronic literature review was performed using PubMed and Google Scholar to identify publications that provided rationales for nonsurgical management of cranial defects in the pediatric population based on size. Titles and abstracts were reviewed by the authors to determine eligibility for full-text analysis. Ineligible studies were categorized and relevant data from fully analyzed texts were recorded.

Results:

Of the 523 articles that were reviewed, 500 were ineligible for full-text analysis due to the following most common reasons: no cranial defect described (227, 45%), did not discuss management of cranial defects (68, 14%), or surgery was performed on all defects in evaluation of a technique or protocol (86, 17%). Ten publications provided relevant data. The suggested size below which surgery was not recommended varied widely between articles. Beyond the age of 1 to 2 years, no general agreement on recommended management in children was found. Craniofacial surgeons had divergent views on the minimum diameter for a “critical” defect and the size for which surgical repair is necessary.

Conclusions:

Little guidance or consensus exists regarding the indications for surgical correction of cranial defects based on the size of the defect. Objective data is needed to classify “clinically critical defects” in the pediatric population.
Improving the robustness of engineered bacteria to nutrient stress using programmed proteolysis
Authors: Szydlo Klara , Ignatova Zoya , Gorochowski Thomas E.
Published: October 2021

The use of short peptide tags in synthetic genetic circuits allows for the tuning of gene expression dynamics and release of amino acid resources through targeted protein degradation. Here, we use elements of the Escherichia coli and Mesoplasma florum transfer-messenger RNA (tmRNA) ribosome rescue systems to compare endogenous and foreign proteolysis systems in E. coli. We characterize the performance and burden of each and show that while both greatly shorten the half-life of a tagged protein, the endogenous system is approximately ten times more efficient. Based on these results, we then demonstrate using mathematical modelling and experiments how proteolysis can improve cellular robustness through targeted degradation of a reporter protein in auxotrophic strains, providing a limited secondary source of essential amino acids that help partially restore growth when nutrients become scarce. These findings provide avenues for controlling the functional lifetime of engineered cells once deployed and increasing their tolerance to fluctuations in nutrient availability.
Distribution and associated factors of hepatic iron – a population-based imaging study
Authors: Maier Lisa , von Krüchten Ricarda , Lorbeer Roberto , Filler Jule , Nattenmüller Johanna , Thorand Barbara , Koenig Wolfgang , Rathmann Wolfgang , Bamberg Fabian , Schlett Christopher L. , Peters Annette , Rospleszcz Susanne
Published: October 2021

Context

Hepatic iron overload can cause severe organ damage. Therefore, an early diagnosis is crucial, and identification of modifiable risk factors could help to prevent manifestations of iron-driven complications.

Objective

To investigate the sex-specific distribution of hepatic iron content (HIC) in a population-based sample, and to identify relevant associated factors from a panel of markers.

Methods

We analysed N=353 participants from a cross-sectional, population-based cohort in Southern Germany (KORA FF4) who underwent whole-body magnetic resonance imaging. HIC was assessed by single-voxel spectroscopy with a high-speed T2-corrected multi-echo technique. A large panel of markers, including anthropometric, genetic and laboratory values as well as behavioural risk factors were assessed. Relevant factors associated with HIC were identified by variable selection based on LASSO regression with bootstrap resampling.

Results

HIC in the study sample (mean age at examination was 56.0 years, 58.4% were men) was significantly lower in women (mean±SD: 39.2±4.1 s-1) than in men (41.8±4.7 s-1, p<0.001). Relevant factors associated with HIC were HbA1c and prediabetes for men, and visceral adipose tissue and age for women. Hepatic fat, alcohol consumption, and a genetic risk score for iron levels were associated with HIC in both sexes.

Conclusion

There are sex-specific associations of HIC with markers of body composition, glucose metabolism and alcohol consumption.
Ex Vivo Culture Models of Hidradenitis Suppurativa for defining molecular pathogenesis and treatment efficacy of novel drugs
Authors: Goliwas Kayla , Kashyap Mahendra P. , Khan Jasim , Sinha Rajesh , Wang Zhiping , Oak Allen S W , Jin Lin , Atigadda Venkatram , Lee Madison B. , Elmets Craig A. , Mukhtar M Shahid , Raman Chander , Deshane Jessy S. , Athar Mohammad
Published: October 2021

Hidradenitis suppurativa (HS) is a complex inflammatory and debilitating skin disease for which no effective treatment is available. This is partly because of the unavailability of suitable human or animal models with which exact pathobiology of the disease can be defined. Here, we describe the development of air-liquid (A-L) interface, liquid-liquid/liquid-submersion (L-S) and bioreactor (Bio) ex vivo skin culture models. All three ex vivo platforms were effective for culturing skin samples up to day-14, with the tissue architecture and integrity remaining intact for at least 3 days for healthy skin while for 14 days for HS skin. Up to day-3, no significant differences were observed in % early apoptotic cells among all three platforms. However, an increase was observed in late apoptotic/necrotic cells in HS skin at day-3 in A-L and Bio culture of HS skin. These cultures efficiently support the growth of various cells populations, including keratinocytes and immune cells. Profiling of the inflammatory genes using HS skin from these ex vivo cultures showed dynamic expression changes at day-3 and day-14. All of these cultures are necessary to represent the inflammatory gene status of HS skin at day-0 suggesting that not all gene clusters are identically altered in each culture method. Similarly, cytokine/chemokine profiling of the supernatant from vehicle- and drug-treated ex vivo HS cultures again showed better prediction of drug efficacy against HS. Overall, development of these three systems collectively provide a powerful tool to uncover the pathobiology of HS progression and screen various drugs against HS.
Frugivore gut passage increases seed germination: an updated meta-analysis
Authors: Rogers Haldre S. , Cavazos Brittany R. , Gawel Ann Marie , Karnish Alex , Ray Courtenay A. , Rose Ethan , Thierry Hugo , Fricke Evan C.
Published: October 2021

Many plants rely on animal mutualists for reproduction. Quantifying how animal mutualists impact plant performance provides a foundation for modelling how change in animal communities affects the composition and functioning of plant communities. We performed a meta-analysis of 2539 experiments, 6 times more than the last comprehensive meta-analysis, examining how gut passage by frugivores influences seed germination. We simultaneously analyzed multiple predictor variables related to study methodology, location, and frugivore identity to disentangle methodological from ecological impacts on effect sizes. We found that gut passage by birds, fish, reptiles, bats, primates, and other mammals on average increased seed germination, but that the magnitude varied across vertebrate groups. The positive effects of gut passage were largely explained by the de-inhibitory effects of pulp removal rather than by the scarification of seed tissues. Some previous studies and meta-analyses that found no effect of gut passage only tested scarification or did not distinguish between these tests of scarification and pulp removal. We found that, for a typical fleshy-fruited plant species, the lack of gut passage reduces germination by 60%. From an evolutionary perspective, this indicates a large risk associated with reliance on animal mutualists that is balanced against the benefits of animal-mediated seed dispersal. From a conservation perspective, this highlights the potential for large demographic consequences of frugivore declines on plant populations. Our database and findings advance quantitative predictions for the role of fruit-frugivore interactions in shaping plant communities in the Anthropocene.
Dynamic remodeling of ribosomes and endoplasmic reticulum in axon terminals of motoneurons
Authors: Deng Chunchu , Moradi Mehri , Reinhard Sebastian , Ji Changhe , Jablonka Sibylle , Hennlein Luisa , Lüningschrör Patrick , Doose Sören , Sauer Markus , Sendtner Michael
Published: October 2021

In neurons, endoplasmic reticulum forms a highly dynamic network that enters axons and presynaptic terminals and plays a central role in Ca2+ homeostasis and synapse maintenance. However, the underlying mechanisms involved in regulation of its dynamic remodeling as well as its function in axon development and presynaptic differentiation remain elusive. Here, we used high resolution microscopy and live cell imaging to investigate rapid movements of endoplasmic reticulum and ribosomes in axons of cultured motoneurons after stimulation with Brain-derived neurotrophic factor. Our results indicate that the endoplasmic reticulum extends into axonal growth cone filopodia where its integrity and dynamic remodeling are regulated mainly by actin and its motor protein myosin VI. Additionally, we found that in axonal growth cones, ribosomes assemble into 80S subunits within seconds and associate with ER in response to extracellular stimuli which describes a novel function of axonal ER in dynamic regulation of local translation.

Summary statement

In axonal growth cones of motoneurons, dynamic remodeling of ER is coordinated through drebrin A-mediated actin and microtubule crosstalk and contributes to local translation as response to BDNF stimulation.
Social and asocial learning in zebrafish are encoded by a shared brain network that is differentially modulated by local activation
Authors: Pinho Júlia , Cunliffe Vincent , Petri Giovanni , Oliveira Rui F.
Published: October 2021

Group living animals can use social and asocial cues to predict the presence of a reward or a punishment in the environment through associative learning. The degree to which social and asocial learning share the same mechanisms is still a matter of debate, and, so far, studies investigating the neuronal basis of these two types of learning are scarce and have been restricted to primates, including humans, and rodents. Here we have used a Pavlovian fear conditioning paradigm in which a social (fish image) or an asocial (circle image) conditioned stimulus (CS) have been paired with an unconditioned stimulus (US=food), and we have used the expression of the immediate early gene c-fos to map the neural circuits associated with social and asocial learning. Our results show that the learning performance is similar with social (fish image) and asocial (circle image) CSs. However, the brain regions involved in each learning type are distinct. Social learning is associated with an increased expression of c-fos in olfactory bulbs, ventral zone of ventral telencephalic area, ventral habenula and ventromedial thalamus, whereas asocial learning is associated with a decreased expression of c-fos in dorsal habenula and anterior tubercular nucleus. Using egonetworks, we further show that each learning type has an associated pattern of functional connectivity across brain regions. Moreover, a community analysis of the network data reveals four segregated functional submodules, which seem to be associated with different cognitive functions involved in the learning tasks: a generalized attention module, a visual response module, a social stimulus integration module and a learning module. Together, these results suggest that, although there are localized differences in brain activity between social and asocial learning, the two learning types share a common learning module and social learning also recruits a specific social stimulus integration module. Therefore, our results support the occurrence of a common general-purpose learning module, that is differentially modulated by localized activation in social and asocial learning.
Modelling homing suppression gene drive in haplodiploid organisms
Authors: Liu Yiran , Champer Jackson
Published: October 2021

Gene drives have shown great promise for suppression of pest populations. These engineered alleles can function by a variety of mechanisms, but the most common is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of heterozygotes. Some potential target species are haplodiploid, in which males develop from unfertilized eggs and thus have only one copy of each chromosome. This prevents drive conversion, a substantial disadvantage compared to diploids where drive conversion can take place in both sexes. Here, we study homing suppression gene drives in haplodiploids and find that a drive targeting a female fertility gene could still be successful. However, such drives are less powerful than in diploids and suffer more from functional resistance alleles. They are substantially more vulnerable to high resistance allele formation in the embryo due to maternally deposited Cas9 and gRNA and also to somatic cleavage activity. Examining spatial models where organisms move over a continuous landscape, we find that haplodiploid suppression drives surprisingly perform nearly as well as in diploids, possibly due to their ability to spread further before inducing strong suppression. Together, these results indicate that gene drive can potentially be used to effectively suppress haplodiploid populations.
Mapping tumor spheroid mechanics in dependence of 3D microenvironment stiffness and degradability by Brillouin microscopy
Authors: Mahajan Vaibhav , Beck Timon , Gregorczyk Paulina , Ruland André , Alberti Simon , Guck Jochen , Werner Carsten , Schlüßler Raimund , Taubenberger Anna V.
Published: October 2021

Altered biophysical properties of cancer cells and of their microenvironment contribute to cancer progression. While the relationship between microenvironmental stiffness and cancer cell mechanical properties and responses has been previously studied using two-dimensional (2D) systems, much less is known about it in a physiologically more relevant 3D context and in particular for multicellular systems. To investigate the influence of microenvironment stiffness on tumor spheroid mechanics, we first generated MCF-7 tumor spheroids within matrix metalloproteinase (MMP)-degradable 3D polyethylene glycol (PEG)-heparin hydrogels, where spheroids showed reduced growth in stiffer hydrogels. We then quantitatively mapped the mechanical properties of tumor spheroids in situ using Brillouin microscopy. Maps acquired for tumor spheroids grown within stiff hydrogels showed elevated Brillouin frequency shifts (hence increased longitudinal elastic moduli) with increasing hydrogel stiffness. Maps furthermore revealed spatial variations of the mechanical properties across the spheroids’ cross-sections. When hydrogel degradability was blocked, comparable Brillouin frequency shifts of the MCF-7 spheroids were found in both compliant and stiff hydrogels, along with similar levels of growth-induced compressive stress. Under low compressive stress, single cells or free multicellular aggregates showed consistently lower Brillouin frequency shifts compared to spheroids growing within hydrogels. Thus, the spheroids’ mechanical properties were modulated by matrix stiffness and degradability as well as multicellularity, and also to the associated level of compressive stress felt by tumor spheroids. Spheroids generated from a panel of invasive breast, prostate and pancreatic cancer cell lines within degradable stiff hydrogels, showed higher Brillouin frequency shifts and less cell invasion compared to those in compliant hydrogels. Taken together, our findings contribute to a better understanding of the interplay between cancer cells and microenvironment mechanics and degradability, which is relevant to better understand cancer progression.
From compartments to gene loops: Functions of the 3D genome in the human brain
Authors: Rahman Samir , Dong Pengfei , Apontes Pasha , Fernando Michael B. , Townsley Kayla G. , Girdhar Kiran , Bendl Jaroslav , Shao Zhiping , Misir Ruth , Tsankova Nadia , Kleopoulos Steven P. , Brennand Kristen J. , Fullard John F. , Roussos Panos
Published: October 2021

The 3D genome plays a key role in the regulation of gene expression. However, little is known about the spatiotemporal organization of chromatin during human brain development. We investigated the 3D genome in human fetal cortical plate and in adult prefrontal cortical neurons and glia. We found that neurons have weaker compartments than glia that emerge during fetal development. Furthermore, neurons form loop domains whereas glia form compartment domains. We show through CRISPRi on CNTNAP2 that transcription is coupled to loop domain insulation. Gene regulation during neural development involves increased use of enhancer-promoter and repressor-promoter loops. Finally, transcription is associated with gene loops. Altogether, we provide novel insights into the relationship between gene expression and different scales of chromatin organization in the human brain.