bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of bariatric surgery on gastroesophageal reflux disease and esophageal motility
Authors: Nguyen Anh D.
Published: April 2021

Purpose of review

Obesity is rapidly increasing in prevalence, and bariatric surgery has become a popular treatment option that can improve all-cause mortality in obese individuals. Gastroesophageal reflux disease (GERD) and esophageal motility disorders are common in the obese population, and the effects of bariatric surgery on these conditions differ depending on the type of bariatric surgery performed.

Recent findings

Laparoscopic adjustable gastric banding has declined in popularity due to its contributions to worsening GERD symptoms and the development of esophageal dysmotility. Although laparoscopic sleeve gastrectomy (LSG) is the most popular type of bariatric surgery, a comprehensive assessment for acid reflux should be performed as LSG has been linked with worsening GERD. Novel methods to address GERD due to LSG include magnetic sphincter augmentation and concomitant fundoplication. Due to the decreased incidence of postoperative GERD and dysmotility compared to other types of bariatric surgeries, Roux-en-Y gastric bypass should be considered for obese patients with GERD and esophageal dysmotility.

Bariatric surgery can affect esophageal motility and contribute to worsening or development of GERD. A thorough workup of gastrointestinal symptoms before bariatric surgery should be performed with consideration for formal testing with high-resolution manometry and pH testing. Based on these results, the choice of bariatric surgery technique should be tailored accordingly to improve clinical outcomes.
Supplementary Bovine Colostrum Feedings to Formula‐Fed Preterm Pigs Improve Gut Function and Reduce Necrotizing Enterocolitis
Authors: Yan Xudong , Sangild Per Torp , Peng Yueming , Li Yanqi , Bering Stine Brandt , Pan Xiaoyu
Published: April 2021

Objectives:

Exclusive feeding with bovine colostrum (BC) protects preterm pigs against necrotizing enterocolitis (NEC) and BC has recently been tested as a supplement to a mother's own milk or formula (FOR) for very preterm infants. Using preterm pigs as a model for infants, we investigated if BC has gut‐ and NEC‐protective effects at different proportions of the daily enteral intake given as BC.

Methods:

Sixty‐eight caesarean‐delivered preterm piglets (90% gestation) were allocated into four groups with increasing proportions of eight daily bolus feedings as BC: BC00 (only FOR feeding), BC25 (25% BC), BC50 (50% BC), or BC75 (75% BC). On day 5, the gut was collected for biochemical analyses.

Results:

Body growth was increased in BC50 and BC75 piglets (2‐fold, P < 0.05 vs BC00). The incidence of mild NEC‐like lesions was similar among groups (67–86%), but BC75 reduced severe NEC‐like lesions (27% vs 79% in BC00, P < 0.05). BC50 and BC75 improved hexose absorption and mucosal structure and reduced gut permeability (P < 0.05 vs BC00), while enzyme activities (lactase, aminopeptidase N and A, dipeptidyl peptidase IV) were improved in all pigs fed BC (P < 0.05). Across the measured variables, beneficial effects were most clear for the BC75 group, including reductions in colon tissue cytokine levels (interleukin 8, interleukin 1β, tumor necrosis factor α) and expression of immune‐ and apoptosis‐related genes (LBP, TLR4, TLR2, IL8, STAT3, IL17, C3, all P < 0.05, relative to BC00).

Conclusion:

A proportion of 50–75% of daily enteral intake as BC is required to improve the intestinal structure, function, immunology, and NEC resistance in preterm piglets also fed formula. Further studies are required to show if and how supplementary BC may support gut development in preterm infants during the immediate postnatal period. It is challenging to translate results on optimal feeding regimens between species, and preterm infants would not receive a majority of their daily enteral intake as BC.
Transition Services for Paediatric Inflammatory Bowel Disease
Authors: Ashton James J. , Narula Priya , Kiparissi Fevronia , Spray Christine , Wilson David C. , Tayler Rachel , Howarth Lucy , Torrente Franco , Deb Protima , Cameron Fiona L. , Muhammed Rafeeq , Paul Thankam , Epstein Jenny , Lawson Maureen , Maginnis Janis , Zamvar Veena , Fagbemi Andrew , Devadason David , Bhavsar Hemant S. , Kammermeier Jochen , Beattie Robert M.
Published: April 2021

Objectives:

Patients with paediatric inflammatory bowel disease (IBD) constitute one of the largest cohorts requiring transition from paediatric to adult services. Standardised transition care improves short and long‐term patient outcomes. This study aimed to detail the current state of transition services for IBD in the United Kingdom (UK).

Methods:

We performed a nationwide study to ascertain current practice, facilities and resources for children and young people with IBD. Specialist paediatric IBD centres were invited to contribute data on: timing of transition/transfer of care; transition resources available including clinics, staff and patient information; planning for future improvement.

Results:

Twenty of 21 (95%) of invited centres responded. Over 90% of centres began the transition process below 16 years of age and all had completed transfer to adult care at 18 years of age. The proportion of patients in the transition process at individual centres varied from 10% to 50%.

Joint clinics were held in every centre, with a mean of 12.9 clinics per year. Adult and paediatric gastroenterologists attended at all sites. Availability of additional team members was patchy across the UK, with dietetic, psychological and surgical attendance available in <50% centres. A structured transition tool was used in 75% of centres. Sexual health, contraception and pregnancy were discussed by <60% of teams.

Conclusions:

This study provides real‐world clinical data on UK‐wide transition services. These data can be used to develop a national strategy to complement current transition guidelines, focused on standardising services whilst allowing for local implementation.
Integration of Lean Visual Management Tools Into Quality Improvement Practices in the Hospital Setting
Authors: Salinas Brianna , Villamin Colleen , Gallardo Luisa Dee
Published: April 2021

Background:

Lean management tools have proven effective in achieving high reliability in health care.

Local Problem:

Unstructured leader rounds, decentralized prevention bundle repositories, and unfavorable patient experience outcomes prompted leaders on a thoracic and cardiovascular surgery unit to find other methods to address these issues and positively impact outcomes.

Methods:

Nurse sensitive indicator prevention bundles, root cause analysis tools, and best practices were used to develop Kamishibai Cards (K-Cards) for each measure targeted.

Interventions:

K-Cards were implemented to standardize processes, engage patients in their care, and promote staff identification of barriers and solutions.

Results:

Nurse-sensitive indicators and patient experience metrics were positively impacted by Kamishibai Rounding. K-Cards promote a state of continuous improvement, which supports sustainability of evidence-based practice and best practices that were implemented.

Conclusions:

K-Cards use high-reliability principles to standardize nursing practice to promote quality outcomes.
Early Life Stress and Chronobiological Rhythms Desynchronization
Authors: Caruso Danila , Palagini Laura , Miniati Mario , Massa Lucia , Marazziti Donatella , Geoffroy Pierre Alexis , Etain Bruno
Published: April 2021

The study aimed at investigating the potential impact of early stressful events on the clinical manifestations of bipolar disorder (BD). A sample of 162 adult individuals with BD was assessed using the Structural Clinical Interview for DSM-5, the Beck Depression Inventory-II, the Young Mania Rating Scale, the Early Trauma Inventory Self Report-Short Form, the Biological Rhythms Interview of Assessment in Neuropsychiatry, the Insomnia Severity Index, and the Scale for Suicide Ideation. A significant path coefficient indicated a direct effect of early life stressors on biological rhythms (coeff. = 0.26; p < 0.001) and of biological rhythms on depressive symptoms (coeff. = 0.5; p < 0.001), suicidal risk (coeff. = 0.3; p < 0.001), and insomnia (coeff. = 0.34; p < 0.001). Data suggested that the desynchronization of chronobiological rhythms might be one mediator of the association between early life stress and the severity of mood symptoms/suicidal ideation in BD. Addressing circadian rhythm alterations in subjects exposed to early stressors would help in preventing consequences of those stressors on BD.
Bone healing: Advances in biology and technology
Authors: Mullis Brian H. , Gudeman Andrew S. , Borrelli Joseph , Crist Brett D. , Lee Mark A. , Evans Andrew R.
Published: April 2021

Fracture healing is a complex cascade of cellular and molecular processes. These processes require the appropriate cellular and molecular environment to ensure the restoration of skeletal stability and resolution of inflammation. In order for fracture healing to occur, the necessary building blocks for bone metabolism and synthesis must be supplied through proper nutrition. Pharmacologic therapies aimed at modulating the inflammatory response to fractures have the potential to interfere with the synthesis of molecules needed for the production of bone. Infection can interfere with, and even prevent normal fracture healing from occurring. Cellular and genetic treatment strategies are actively being developed to target deficiencies, and bridge gaps that can influence how fractures heal. Evolving technologies, including nutritional supplementation, pharmacotherapies, antibiotics, surgical techniques, as well as genetic and cellular therapies, have the potential to enhance, optimize, and even revolutionize the process of fracture healing.
Regulation of orthopaedic devices: Future implications for research and innovation
Authors: Donnelley Claire A. , Devlin Vincent J. , Harris Mitchel B. , Poggie Robert A. , Sanders Roy W. , Morshed Saam
Published: April 2021

The conception-to-market development of orthopaedic devices occurs across the total product life cycle including device design and preclinical testing, clinical investigations to support marketing applications, and monitoring of device performance after market introduction. This process involves industry, regulatory agencies, health care providers, engineers, scientists, and patients. The Food and Drug Administration (FDA) is responsible for regulating medical devices in the United States, and uses a 3-tier classification system based on the level of control necessary to provide reasonable assurance of safety and effectiveness. Classification directs the required regulatory pathway and premarket submission type. Variations in global regulations, particularly between the United States, European Economic Area (EEA), and the United Kingdom (UK), may impact industry response to orthopaedic device development. Changing device innovation and reimbursement models have led to the consolidation of market share among larger companies. Although larger companies are better able to cope with more rigorous regulatory requirements, this leads to decreased competition and increased upward price pressure. To assist with the complex regulatory processes, the FDA offers pre-submission assistance as an opportunity for early collaboration and discussion about the medical device or device-led combination product submissions. Orthopaedic organizations, such as the Orthopaedic Trauma Association (OTA), may assist in postmarket device surveillance through the coordinated development and maintenance of clinical data registries. Such registries can longitudinally follow patients with a specific orthopaedic pathology or device usage, and monitor outcomes towards improvements in next-generation device development. As technology evolves, the nexus of regulation, industry, and patient outcome monitoring will continue to support safe and effective device innovation.
Patient-reported benefits of bone-anchored transfemoral prostheses as assessed by MedTech20: A general outcome measure for medical products
Authors: Hagberg Kerstin , Brodtkorb Thor-Henrik
Published: April 2021

Background:

The medical community demands evidence for the benefits of medical devices such as bone-anchored prostheses (BAPs). MedTech20  is a novel instrument aiming to address general benefits of medical devices.

Objective:

To describe general patient-reported benefits of BAPs measured with MedTech20.

Study Design:

This is a cross-sectional descriptive survey.

Methods:

Patients treated in Sweden who had used a BAP for >1 year were mailed the MedTech20  Questionnaire. Responses to each attribute were described, and the MedTech20   Index (0-1), in which a higher figure represents larger benefits from the product, was calculated. Index values were compared based on demographic variables (sex, unilateral or bilateral transfemoral amputation (TFA), and those having experienced any complication of implant parts or the prosthetic connection device).

Results:

The response rate was 72%. The 62 participants (41 men and 21 women; mean age 57 years) had 11 ± 6.9 mean years of BAP experience. Single attributes stated as highly relevant and with high benefit for BAPs included perceived reliability, perceived safety, sense of control of the disability, facilitation of movement outside home, no discomfort at use, and ease of use. Attributes with less relevance included aid to remember tasks, reduction of barriers to a good sleep, and reduced sense of compromised integrity. The MedTech20  Index was 0.655 ± 0.188 and was not statistically significantly different based on any of the demographic variables.

Conclusions:

By using a general measure on attributes of medical devices, this study provides new insights strengthening the evidence regarding the benefits that BAPs provide for patients with TFA who had difficulties with socket-suspended prostheses.
Are Cannabis, Cannabis-Derived Products, and Synthetic Cannabinoids a Therapeutic Tool for Rheumatoid Arthritis? A Friendly Summary of the Body of Evidence
Authors: Schulze-Schiappacasse Clara , Durán Josefina , Bravo-Jeria Rocío , Verdugo-Paiva Francisca , Morel Macarena , Rada Gabriel
Published: April 2021

Background

Symptom management in rheumatoid arthritis (RA) remains a complex challenge. Widespread use of cannabis-based medicines for a myriad of symptoms has fostered rheumatology patients' interest. However, their safety and efficacy in RA remain unclear.

Objective

The aim of this study was to perform a structured summary of the body of evidence in order to determine whether cannabis, cannabis-derived products, and synthetic cannabinoids are an effective treatment for rheumatoid arthritis.

Methods

An electronic search in Epistemonikos database was performed to identify systematic reviews and their primary studies that addressed our clinical question. The body of evidence was collected in a pivot table in Epistemonikos. Information and data from the primary studies were extracted from the identified reviews. Finally, extracted data were reanalyzed, and a summary of findings table was generated using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results

Twenty-six systematic reviews were identified which included in total only 1 randomized trial assessing our clinical question.

Conclusions

Cannabis, cannabis-derived products and synthetic cannabinoids may slightly reduce disease activity in patients with RA. Its use may result in little to no difference in pain reduction and may slightly increase nervous system adverse events. The evidence is very uncertain about the effect of cannabis, cannabis-derived products, and synthetic cannabinoids on serious adverse events risk.
Reconstruction of Large Tissue Defects After the Resection of Brain Tumors Using a Skin Flap With Vascular Pedicle
Authors: Bai Jie , Fu Jiayue , Xiao Xinru
Published: April 2021

The reconstruction of large tissue defects after the resection of brain tumors is challenging for every neurosurgeon. The authors describe the benefits of a skin flap with vascular pedicle in the reconstruction of large tissue defects after the resection of brain tumors. In this retrospective analysis, a skin flap with vascular pedicle reconstruction was used in 5 patients who underwent intracranial tumor resection, accompanied by tissue defects, cerebrospinal fluid leakage and scalp infection. The surgical techniques are described, and the outcomes were discussed. The harvested flaps showed well-vascularized healing of the transplanted skin without partial necrosis in all 5 patients. One patient had cerebrospinal rhinorrhea, which was successfully treated by endoscopic repair. Another patient had cerebrospinal fluid leakage, which was successfully treated by continuous lumbar drainage. A skin flap with vascular pedicle is an effective choice for the reconstruction of large tissue defects after the resection of brain tumors.
Chimeric Latissimus Dorsi Flap in One-Stage Reconstruction of Depressor Muscle Dysfunction and Depression Deformity in the Perimandibular Area
Authors: Ogawa Kazuya , Okazaki Mutsumi , Tanaka Kentaro , Uemura Noriko , Homma Tsutomu
Published: April 2021

Background:

Depression deformity and paralysis of depressor muscles (DMs) may occur following tumor resection in the perimandibular region. Obtaining satisfactory results is challenging. The authors report 3 cases of 1-stage reconstruction by transferring neurovascular chimeric latissimus dorsi (LD) musculo-adipose flaps, with satisfactory results.

Methods:

Three patients with depression deformity and DMs dysfunction after tumor resection in the perimandibular region underwent chimeric LD flap transfer. The flap comprised 1 portion with adipose tissue for augmentation, and the other contained muscle bellies with 1 or 2 neural pedicle (s) for DM reanimation. In case 1, the neural pedicle was sutured to the contralateral marginal mandibular branch. In case 2, the neural pedicle was sutured to the ipsilateral marginal mandibular branch. In case 3, the neural pedicle was sutured to both branches of the facial nerve.

Results:

All patients were satisfied with the deformity corrections. However, contractions of the transferred muscles varied. Case 1 showed insufficient contraction. Case 2 had excessive muscle contraction. In case 3, the muscle had double innervation, and well-balanced contraction was maintained for 3 years.

Conclusions:

Neurovascular chimeric LD flaps are versatile and useful for secondary reconstruction after tumor resection for functional loss of mimetic muscles. The ipsilateral facial nerve may be an effective motor source.
Use of Serial Flap Transfer Technique in En Bloc Reconstruction of Extensive Soft Tissue Defects in the Head and Neck
Authors: Zang Mengqing , Zhu Shan , Chen Bo , Li Shanshan , Han Tinglu , Liu Yuanbo
Published: April 2021

En bloc reconstruction of extensive head and neck defects is feasible with matched tissue from the medial arm or chest. Nevertheless, the donor site faces significant morbidity following massive cutaneous flap harvesting. The serial flap transfer technique can increase the reconstructive ability of these flaps and minimize the donor site morbidity. A retrospective review was conducted from 2016 to 2020 on all patients who had undergone extensive head and neck reconstruction with the serial flap transfer technique. En bloc reconstruction of defects in the head and neck was performed using expanded perforator-plus flaps from the medial arm or chest; various flaps from the back were used to close the donor-site defects. Flap type, flap survival, complications, and revision procedures were assessed. This case series included 16 patients. The donor site of the chest or medial arm was successfully closed with the assistance of the thoracodorsal artery perforator flap, the latissimus dorsi myocutaneous flap, ortheparascapular flap. A medial arm flap with a width of 15 cm and a chest flap with a 16 cm width could be transferred with the primary closure of the donor sites. All flaps survived, except 1 had marginal necrosis. Complications occurred in 2 patients and were successfully managed nonsurgically. Both the recipient and donor sites were restored with good aesthetic results. Application of the serial flap transfer technique in extensive head and neck reconstruction decreases the donor site morbidity to a minimum and improves the overall outcomes.
Optimizing Trauma Systems
Authors: Ben Beck  , Tack Guido , Cameron Peter , Smith Karen , Gabbe Belinda
Published: April 2021

Objective:

The aim of this study was to develop a data-driven approach to assessing the influence of trauma system parameters and optimizing the configuration of the Victorian State Trauma System (VSTS).

Summary Background Data:

Regionalized trauma systems have been shown to reduce the risk of mortality and improve patient function and health-related quality of life. However, major trauma case numbers are rapidly increasing and there is a need to evolve the configuration of trauma systems.

Methods:

A retrospective review of major trauma patients from 2016 to 2018 in Victoria, Australia. Drive times and flight times were calculated for transport to each of 138 trauma receiving hospitals. Changes to the configuration of the VSTS were modeled using a Mixed Integer Linear Programming algorithm across 156 simulations.

Results:

There were 8327 patients included in the study, of which 58% were transported directly to a major trauma service (MTS). For adult patients, the proportion of patients transported directly to an MTS increased with higher transport time limit, greater probability of helicopter emergency medical service utilization, and lower hospital patient threshold numbers. The proportion of adult patients transported directly to an MTS varied from 66% to 90% across simulations. Across all simulations for pediatric patients, only 1 pediatric MTS was assigned.

Conclusions:

We have developed a robust and data-driven approach to optimizing trauma systems. Through the use of geospatial and mathematical models, we have modeled how potential future changes to trauma system characteristics may impact on the optimal configuration of the system, which will enable policy makers to make informed decisions about health service planning into the future.
IDEAL-D Framework for Device Innovation
Authors: Marcus Hani J. , Bennett Amy , Chari Aswin , Day Toni , Hirst Allison , Hughes-Hallett Archie , Kolias Angelos , Kwasnicki Richard M. , Martin Janet , Rovers Maroeska , Squire Sarah E. , McCulloch Peter
Published: April 2021

Objective:

To extend the IDEAL framework for device innovation, IDEAL-D, to include the preclinical stage of development (stage 0).

Background:

In previous work, the IDEAL collaboration has proposed frameworks for new surgical techniques and complex therapeutic technologies, the central tenet being that development and evaluation can and should proceed together in an ordered and logical manner that balances innovation and safety.

Methods:

Following agreement at the IDEAL Collaboration Council, a multidisciplinary working group was formed comprising 12 representatives from healthcare, academia, industry, and a patient advocate. The group conducted a series of discussions following the principles used in the development of the original IDEAL framework. Importantly, IDEAL aims for maximal transparency, optimal validity in the evaluation of primary effects, and minimization of potential risk to patients or others. The proposals were subjected to further review and editing by members of the IDEAL Council before a final consensus version was adopted.

Results:

In considering which studies are required before a first-in-human study, we have: (1) classified devices according to what they do and the risks they carry, (2) classified studies according to what they show about the device, and (3) made recommendations based on the principle that the more invasive and high risk a device is, the greater proof required of their safety and effectiveness before progression to clinical studies (stage 1).

Conclusions:

The proposed recommendations for preclinical evaluation of medical devices represent a proportionate and pragmatic approach that balances the de-risking of first-in-human translational studies against the benefits of rapid translation of new devices into clinical practice.
Coaching in Surgical Education
Authors: Louridas Marisa , Sachdeva Ajit K. , Yuen Andrew , Blair Patrice , MacRae Helen
Published: April 2021

Objective:

The objectives of this study were to review the coaching literature to (1) characterize the criteria integral to the coaching process, specifically in surgery, and (2) describe how these criteria have been variably implemented in published studies.

Background:

Coaching is a distinct educational intervention, but within surgery the term is frequently used interchangeably with other more established terms such as teaching and mentoring.

Methods:

A systematic search was performed of the MEDLINE and Cochrane databases to identify studies that used coach/coaching as an intervention for surgeons for either technical or nontechnical skills. Study quality was evaluated using the Medical Education Research Study Quality Instrument (MERSQI).

Results:

A total of 2280 articles were identified and after screening by title, abstract and full text, 35 remained. Thirteen coaching criteria (a–m) were identified in 4 general categories: 1. overarching goal (a. refine performance of an existing skill set), 2. the coach (b. trusting partnership, c. avoids assessment, d. 2-way communication), the coachee (e. voluntary participation, f. self-reflection, g. goal setting, h. action plan, i. outcome evaluation), and the coach-coachee rapport (j. coaching training, k. structured coaching model, l. non-directive, m. open ended questions). Adherence to these criteria ranged from as high of 73% of studies (voluntary participation of coach and coachee) to as low as 7% (use of open-ended questions).

Conclusions:

Coaching is being used inconsistently within the surgical education literature. Our hope is that with establishing criteria for coaching, future studies will implement this intervention more consistently and allow for better comparison and generalization of results.
The impact of COVID-19 on gambling and gambling disorder: emerging data
Authors: Hodgins David C. , Stevens Rhys M.G.
Published: April 2021

Purpose of review

The lockdown response to the COVID-19 pandemic has significantly impacted commercial gambling in many jurisdictions around the world. The goal of this review is to systematically identify and describe the survey data and findings to date examining the effect on individual gambling and gambling disorder.

Recent findings

Of the 17 publications meeting inclusion criteria, the majority reported cross-sectional assessments (n = 11, 65%) and remainder were longitudinal in that they had earlier gambling data for participants (n = 6, 35%). Not surprisingly given the closure of land-based gambling, an overall reduction in gambling frequency and expenditure was reported in all studies. The estimate of the proportion of participants in both the general population and the population that gambles who increased overall gambling or online gambling was variable. The most consistent correlates of increased gambling during the lockdown were increased problem gambling severity, younger age groups, and being male.

These results suggest that the impacts of the COVID-19 pandemic on gambling and problematic gambling are diverse – possibly causing a reduction in current or future problems in some, but also promoting increased problematic gambling in others. The longer-term implications of both the reduction in overall gambling, and the increase in some vulnerable groups are unclear, and requires assessment in subsequent follow-up studies. However, in the short term, individuals with existing gambling problems should be recognized as a vulnerable group.
Cross-species comparisons andin vitromodels to study tempo in development and homeostasis
Authors: Rayon Teresa , Briscoe James
Published: April 2021

Time is inherent to biological processes. It determines the order of events and the speed at which they take place. However, we still need to refine approaches to measure the course of time in biological systems and understand what controls the pace of development. Here, we argue that the comparison of biological processes across species provides molecular insight into the timekeeping mechanisms in biology. We discuss recent findings and the open questions in the field and highlight the use ofin vitrosystems as tools to investigate cell-autonomous control as well as the coordination of temporal mechanisms within tissues. Further, we discuss the relevance of studying tempo for tissue transplantation, homeostasis and lifespan.
Homology of process: developmental dynamics in comparative biology
Authors: DiFrisco James , Jaeger Johannes
Published: April 2021

Comparative biology builds up systematic knowledge of the diversity of life, across evolutionary lineages and levels of organization, starting with evidence from a sparse sample of model organisms. In developmental biology, a key obstacle to the growth of comparative approaches is that the concept of homology is not very well defined for levels of organization that are intermediate between individual genes and morphological characters. In this paper, we investigate what it means for ontogenetic processes to be homologous, focusing specifically on the examples of insect segmentation and vertebrate somitogenesis. These processes can be homologous without homology of the underlying genes or gene networks, since the latter can diverge over evolutionary time, while the dynamics of the process remain the same. Ontogenetic processes like these therefore constitute a dissociable level and distinctive unit of comparison requiring their own specific criteria of homology. In addition, such processes are typically complex and nonlinear, such that their rigorous description and comparison requires not only observation and experimentation, but also dynamical modelling. We propose six criteria of process homology, combining recognized indicators (sameness of parts, morphological outcome and topological position) with novel ones derived from dynamical systems modelling (sameness of dynamical properties, dynamical complexity and evidence for transitional forms). We show how these criteria apply to animal segmentation and other ontogenetic processes. We conclude by situating our proposed dynamical framework for homology of process in relation to similar research programmes, such as process structuralism and developmental approaches to morphological homology.
Small RNAs and chromatin in the multigenerational epigenetic landscape ofCaenorhabditis elegans
Authors: Frolows Natalya , Ashe Alyson
Published: April 2021

For decades, it was thought that the only heritable information transmitted from one individual to another was that encoded in the DNA sequence. However, it has become increasingly clear that this is not the case and that the transmission of molecules from within the cytoplasm of the gamete also plays a significant role in heritability. The roundworm,Caenorhabditis elegans,has emerged as one of the leading model organisms in which to study the mechanisms of transgenerational epigenetic inheritance (TEI). Collaborative efforts over the past few years have revealed that RNA molecules play a critical role in transmitting transgenerational responses, but precisely how they do so is as yet uncertain. In addition, the role of histone modifications in epigenetic inheritance is increasingly apparent, and RNA and histones interact in a way that we do not yet fully understand. Furthermore, both exogenous and endogenous RNA molecules, as well as other environmental triggers, are able to induce heritable epigenetic changes that affect transcription across the genome. In most cases, these epigenetic changes last only for a handful of generations, but occasionally can be maintained much longer: perhaps indefinitely. In this review, we discuss the current understanding of the role of RNA and histones in TEI, as well as making clear the gaps in our knowledge. We also speculate on the evolutionary implications of epigenetic inheritance, particularly in the context of a short-lived, clonally propagating species.

This article is part of the theme issue ‘How does epigenetics influence the course of evolution?’
Evaluation of the SARS-CoV-2 inactivation efficacy associated with buffers from three kits used on high-throughput RNA extraction platforms
Authors: Thom Ruth E. , Eastaugh Lin S. , O’Brien Lyn M. , Ulaeto David O. , Findlay James S. , Smither Sophie J. , Phelps Amanda L. , Stapleton Helen L. , Hamblin Karleigh A. , Weller Simon A.
Published: April 2021

Rapid and demonstrable inactivation of SARS-CoV-2 is crucial to ensure operator safety during high-throughput testing of clinical samples. The inactivation efficacy of SARS-CoV-2 was evaluated using commercially available lysis buffers from three viral RNA extraction kits used on two high-throughput (96-well) RNA extraction platforms (Qiagen QiaCube HT and the ThermoFisher Kingfisher Flex) in combination with thermal treatment. Buffer volumes and sample ratios were chosen for their optimised suitability for RNA extraction rather than inactivation efficacy and tested against a representative sample type; SARS-CoV-2 spiked into viral transport medium (VTM). A lysis buffer from the MagMax Pathogen RNA/DNA kit (ThermoFisher), used on the Kingfisher Flex, which included guanidinium isothiocycnate (GITC), a detergent, and isopropanol demonstrated a minimum inactivation efficacy of 1 x 105TCID50/ml. An alternative lysis buffer from the MagMax Viral/Pathogen Nucleic Acid kit (Thermofisher) also used on the Kingfisher Flex and the lysis buffer from QIAamp 96 Virus QIAcube HT Kit (Qiagen) used on the QiaCube HT (both of which contained GITC and a detergent) reduced titres by 1 x 104TCID50/ml but did not completely inactivate the virus. Heat treatment alone (15 minutes, 68 °C) did not completely inactivate the virus, demonstrating a reduction of 1 x 103TCID50/ml. When inactivation methods included both heat treatment and addition of lysis buffer, all methods were shown to completely inactivate SARS-CoV-2 inactivation against the viral titres tested. Results are discussed in the context of the operation of a high-throughput diagnostic laboratory.
Identifying essential genes across eukaryotes by machine learning
Authors: Beder Thomas , Aromolaran Olufemi , Dönitz Jürgen , Tapanelli Sofia , Adedeji Eunice O. , Adebiyi Ezekiel , Bucher Gregor , Koenig Rainer
Published: April 2021

Identifying essential genes on a genome scale is resource intensive and has been performed for only a few eukaryotes. For less studied organisms essentiality might be predicted by gene homology. However, this approach cannot be applied to non-conserved genes. Additionally, divergent essentiality information is obtained from studying single cells or whole, multi-cellular organisms, and particularly when derived from human cell line screens and human population studies. We employed machine learning across six model eukaryotes and 60,381 genes, using 41,635 features derived from sequence, gene functions and network topology. Within a leave-one-organism-out cross-validation, the classifiers showed a high generalizability with an average accuracy close to 80% in the left-out species. As a case study, we applied the method toTribolium castaneumand validated predictions experimentally yielding similar performance. Finally, using the classifier based on the studied model organisms enabled linking the essentiality information of human cell line screens and population studies.
Endothelial metastasis-associated protein 1 (MTA1) is an essential molecule for angiogenesis
Authors: Ishikawa Mizuho , Osaki Mitsuhiko , Uno Narumi , Ohira Takahito , Kugoh Hiroyuki , Okada Futoshi
Published: April 2021

Our previous study revealed that metastasis-associated protein 1 (MTA1), expressed in endothelial cells acts as a factor promoting tube formation. In this study, we aimed to clarify the importance of MTA1 in tube formation usingMTA1-knockout endothelial cells (MTA1-KO MSS31 cells). Tube formation was strongly suppressed in MTA1-KO MSS31 cells, whereas MTA1-overexpressed MTA1-KO MSS31 cells regained the ability to form tube-like structures. Furthermore, MTA1-KO MSS31 cells showed higher phosphorylation of non-muscle myosin heavy chain IIa (NMIIa), which resulted in suppression of tube formation; this was attributed to a decrease of MTA1– S100 calcium-binding protein A4 (S100A4) complex formation. Moreover, inhibition of tube formation in MTA1-KO MSS31 cells could not be rescued by stimulation with vascular endothelial growth factor (VEGF). These results demonstrated that MTA1 is an essential molecule for angiogenesis, and that it may be involved in different steps of the angiogenic process compared to the VEGF–VEGF receptor 2 (VEGFR2) pathway. Our findings showed that endothelial MTA1 and its pathway are promising targets for inhibiting tumor angiogenesis, supporting the development of MTA1-based anti-angiogenic therapies.
Smell-induced gamma oscillations in human olfactory cortex are required for accurate perception of odor identity
Authors: Yang Qiaohan , Zhou Guangyu , Noto Torben , Templer Jessica , Schuele Stephan , Rosenow Joshua , Lane Gregory , Zelano Christina
Published: April 2021

Studies of neuronal oscillations have contributed substantial insight into the mechanisms of visual, auditory and somatosensory perception. However, progress in such research in the human olfactory system has lagged behind. As a result, the electrophysiological properties of the human olfactory system are poorly understood, and in particular, whether stimulus-driven high frequency oscillations play a role in odor processing is unknown. Here, we used direct intracranial recordings from human piriform cortex during an odor identification task to show that three key oscillatory rhythms are an integral part of the human olfactory cortical response to smell: odor induces theta, beta and gamma rhythms in human piriform cortex. We further show that these rhythms have distinct relationships with perceptual behavior. Odor-elicited gamma oscillations occur only during trials in which the odor is accurately perceived, and features of gamma oscillations predict odor identification accuracy, suggesting they are critical for odor identity perception in humans. We also found that the amplitude of high-frequency oscillations is organized by the phase of low frequency signals shortly following sniff onset, only when odor is present. Our findings reinforce previous work on theta oscillations, suggest that gamma oscillations in human piriform cortex are important for perception of odor identity, and constitute a robust identification of the characteristic electrophysiological response to smell in the human brain. Future work will determine whether the distinct oscillations we identified reflect distinct perceptual features of odor stimuli.
Behavioral clusters revealed by end-to-end decoding from microendoscopic imaging
Authors: Chang Chia-Jung , Guo Wei , Zhang Jie , Newman Jon , Sun Shao-Hua , Wilson Matt
Published: April 2021

In vivocalcium imaging using head-mounted miniature microscopes enables tracking activity from neural populations over weeks in freely behaving animals. Previous studies focus on inferring behavior from a population of neurons, yet it is challenging to extract neuronal signals given out-of-focus fluorescence in endoscopic data. Existing analysis pipelines include regions of interest (ROIs) identification, which might lose relevant information from false negatives or introduce unintended bias from false positives. Moreover, these methods often require prior knowledge for parameter tuning and are time-consuming for implementation. Here, we develop an end-to-end decoder to predict the behavioral variables directly from the raw microendoscopic images. Our framework requires little user input and outperforms existing decoders that need ROI extraction. We show that neuropil/background residuals carry additional behaviorally relevant information. Video analysis further reveals an optimal decoding window and dynamics between residuals and cells. Critically, saliency maps reveal the emergence of video-decomposition across our decoder, and identify distinct clusters representing different behavioral aspects. Together, we present a framework that is efficient for decoding behavior from microendoscopic imaging, and may help discover functional clustering for a variety of imaging studies.
The Expression of Angiopoietin-1 and −2 in the Osteogenesis of Mesenchymal Stem Cells
Authors: Chen Jinwen , Yang Guangchan , Guo Jie , Liu Yuqin , Guo Jinchen , Suo Jiatao , Yu Hongyou
Published: April 2021

Objective

The objectives of this study are to clarify whether rat bone marrow derived Mesenchymal stem cells (MSCs) express Ang1 and Ang2 and their expression in the process of osteogenesis in vitro.

Material and Methods

MSCs were cultured from rat tibia bone marrow cells and the hemopoietic stem cells were deplete by consistently replacement of the culture medium. The MSCs were induced osteogenesis with mineralization conditional medium and Immunohistochemical and immunofluorescent staining were performed to assess the expression of Ang1 and Ang2.

Results

The method used to expand rat MSCs in vitro was applicable, and the cell morphology is spindle-like shape that is consistent with the privous reports. The immunohistochemical staining results showed that both Ang1 and Ang2 were expressed by rat MSCs. Both Ang1 and Ang2 were up-regulated in the process of osteogenesis of rat MSCs.

Conclusion

Rat MSCs express both Ang1 and Ang2 which might play critical roles in the osteogenesis in vitro.
Cytoplasmic zinc regulates IL-1β production by monocytes/macrophages via mTORC1-induced glycolysis in rheumatoid arthritis (RA)
Authors: Kim Bonah , Kim Hee Young , Yoon Bo Ruem , Yeo Jina , Yu Kyung-Sang , Kim Hyeon Chang , Park Jin Kyun , Kang Seong Wook , Lee Won-Woo
Published: April 2021

The essential micronutrient zinc plays regulatory roles in immune responses through its ability to affect signaling pathways. In activated monocytes/macrophages, signaling networks mediate metabolic reprogramming in order to meet the demands of participating in immune responses. Despite its known immunoregulatory roles, the effect of zinc on metabolic reprogramming in monocytes/macrophages remains unclear. Here, we demonstrate that cytoplasmic bioavailable zinc is essential for regulating IL-1β production in activated human monocytes/macrophages downstream of mTORC1-induced glycolysis. The cytoplasmic zinc level was influenced by extracellular zinc concentration through a zinc-specific importer, Zip8, which was markedly increased in monocytes of patients with rheumatoid arthritis (RA), a chronic inflammatory disease, and even in LPS-stimulated monocytes/macrophages of healthy individuals. Mechanically, phosphorylation of S6 kinase, a substrate of mTORC1, was significantly enhanced by zinc-mediated inhibition of PP2A, an S6 kinase phosphatase. As a result, IL-1β production was increased due to the activation of mTORC1-induced glycolysis. The expression of Zip8 and MT2A, a zinc-inducible gene, and the phosphorylation of S6 kinase by monocytes of RA patients was significantly enhanced compared with those of HCs and Zip8 levels positively correlated with RA clinical parameters, suggesting that Zip8-mediated zinc influx is related to inflammatory conditions. These results provide insight into the role of cytoplasmic bioavailable zinc in the metabolic reprogramming of human monocytes/macrophages which is an essential process for inflammatory responses.

One Sentence Summary

Cytoplasmic zinc regulates IL-1β production in monocytes/macrophages downstream of mTORC1-S6K-induced glycolysisviazinc-mediated inhibition of PP2A.
Validation and Application of a Protocol for the Extraction and Quantitative Analysis of Sphingomyelin in Erythrocyte Membranes of Patients with NAFLD
Authors: Papadopoulos Charalampos , Mimidis Konstantinos , Tentes Ioannis , Tente Thaleia , Anagnostopoulos Konstantinos
Published: April 2021

A set of constituents of the erythrocyte membrane lipidome has been proposed to serve as biomarkers for liver disease and acute coronary syndrome. In erythrocytes, sphingomyelin hydrolysis provides ceramide, a signaling lipid necessary for phosphatidylserine exposure and eryptosis. Phosphatidylserine exposure further amplifies hepatic inflammation and fibrosis during non-alcoholic fatty liver disease (NAFLD). In this study, we developed and applied a quantitative TLC for erythrocyte membrane sphingomyelin of NAFLD patients. We also compared 10 extraction methods for the isolation of sphingomyelin from erythrocytes. For quantitative TLC, lipids were separated in Silica gel 60 F254 using a mixture of chloroform/methanol/acetic acid/water (60/50/1/4) (v/v/v/v). The separated lipids were stained in a chamber containing iodine, and the intensity of each of the primary colors (red, green, blue) and the sum of the Red plus Green colors (R+G) was analyzed. The method was linear over a wide range of concentrations, presented acceptable precision (inter-day CV(%) 0.34, 0.006 and 0.44 for 2.5, 5.0 and 10 μg, respectively), good accuracy (recovery range 85.2-97.1%), and excellent limit of detection (0.137 μg/spot) and limit of quantification (0.41 μg/spot). Using this quantitation method, we compared various lipid extraction methods and found that lipid extraction with methanol led to higher yield of erythrocyte sphingomyelin (135.35±1.04% recovery, compared to the Folch method). Application of these methods showed that erythrocytes from NAFLD patients (9 men, 15 women, 57.95±11.11 years old) contained statistically significantly less sphingomyelin (829.82±511.60 vs 1892.08±606.25 μg/ml of packed erythrocytes) compared to healthy controls (4 men, 6 women, 39.3±15.55 years old).