bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptation to DNA damage as a bet-hedging mechanism in a fluctuating environment
Authors: Roux Pierre , Salort Delphine , Xu Zhou
Published: March 2021

In response to DNA damage, efficient repair is essential for cell survival and genome integrity. In eukaryotes, the DNA damage checkpoint is a signalling pathway that coordinates this response and arrests the cell cycle to provide time for repair. However, when repair fails or when the damage is not repairable, cells can eventually bypass the DNA damage checkpoint and undergo cell division despite persistent damage, a process called adaptation to DNA damage. Interestingly, adaptation occurs with a delayed timing compared to repair and shows a large variation in time, two properties that may provide a survival advantage at the population level without interfering with repair. Here, we explore this idea by mathematically modelling cell survival in response to DNA damage and focusing on adaptation parameters. We find that the delayed adaptation timing indeed maximizes survival, but its heterogeneity is beneficial only in a fluctuating damage-inducing environment. Finally, we show that adaptation does not only contribute to survival but also to genome instability and mutations, which might represent another criterion for its selection through-out evolution. Overall, we propose that adaptation can act as a bet-hedging mechanism for cell survival in response to DNA damage.
Single-molecule conformational dynamics of a transcription factor reveals a continuum of binding modes controlling association and dissociation
Authors: Chen Wei , Lu Wei , Wolynes Peter G. , Komives Elizabeth A.
Published: March 2021

Binding and unbinding of transcription factors to DNA are kinetically controlled to regulate the transcriptional outcome. Control of the release of the transcription factor NF-κB from DNA is achieved through accelerated dissociation by the inhibitor protein IκBα. Using single-molecule FRET, we observe a continuum of conformations of NF-κB in free and DNA-bound states interconverting on the subseconds to minutes timescale, comparable toin vivobinding on the seconds timescale, suggesting that structural dynamics directly control binding kinetics. Much of the DNA-bound NF-κB is partially bound, allowing IκBα invasion to facilitate DNA dissociation. IκBα induces a locked conformation where the DNA-binding domains of NF-κB are too far apart to bind DNA, whereas the loss-of-function IκBα mutant retains the NF-κB conformational ensemble. Overall, our results suggest a novel mechanism with a continuum of binding modes for controlling association and dissociation of transcription factors.
The phytonutrient cinnamaldehyde limits intestinal inflammation and enteric parasite infection
Authors: Zhu Ling , Andersen-Civil Audrey I.S. , Myhill Laura J. , Thamsborg Stig M. , Kot Witold , Krych Lukasz , Nielsen Dennis S. , Blanchard Alexandra , Williams Andrew R.
Published: March 2021

Phytonutrients such as cinnamaldehyde (CA) have been studied for their effects on metabolic diseases, but their influence on mucosal inflammation and immunity to enteric infection are not well documented. Here, we show that consumption of CA significantly down-regulates transcriptional pathways connected to inflammation in the small intestine of mice. During infection with the enteric helminth Heligomosomoides polygyrus, CA-treated mice displayed higher growth rates and less worms, concomitant with altered T-cell populations in mesenteric lymph nodes. Furthermore, infection-induced changes in gene pathways connected to cell cycle and mitotic activity were counteracted by CA. Mechanically, CA did not appear to exert activity through a prebiotic effect, as CA treatment did not significantly change the composition of the gut microbiota. Instead, in vitro experiments showed that CA directly induced xenobiotic metabolizing pathways in intestinal epithelial cells and suppressed endotoxin-induced inflammatory responses in macrophages. Thus, CA down-regulates inflammatory pathways in the intestinal mucosa and regulates host responses to enteric infection. These properties appear to be largely independent of the gut microbiota and instead connected to CA’s ability to induce antioxidant pathways in intestinal cells. Our results encourage further investigation into the use of CA and related phytonutrients as functional food components to promote intestinal health in humans and animals.
Structural basis of LhcbM5-mediated state transitions in green algae
Authors: Pan Xiaowei , Tokutsu Ryutaro , Li Anjie , Takizawa Kenji , Song Chihong , Murata Kazuyoshi , Yamasaki Tomohito , Liu Zhenfeng , Minagawa Jun , Li Mei
Published: March 2021

In green algae and plants, state transitions serve as a short-term light acclimation process to regulate light harvesting capacity of photosystems I and II (PSI and PSII). During the process, a portion of the light-harvesting complexes II (LHCII) are phosphorylated, dissociate from PSII and bind PSI to form PSI-LHCI-LHCII supercomplex. Here we report high-resolution structures of PSI-LHCI-LHCII supercomplex fromChlamydomonas reinhardtii, revealing the mechanism of assembly between PSI-LHCI complex and two phosphorylated LHCII trimers containing all four types of LhcbM proteins. Two specific LhcbM isoforms, namely LhcbM1 and LhcbM5, directly interact with the PSI core through their phosphorylated amino-terminal regions. Furthermore, biochemical and functional studies on mutant strains lacking either LhcbM1 or LhcbM5 indicate that only LhcbM5 is indispensable in the supercomplex formation. The results unraveled the specific interactions and potential excitation energy transfer routes between green algal PSI and two phosphorylated LHCIIs.
Ribosomal RNA methylation by GidB modulates discrimination of mischarged tRNA
Authors: Bi Zhuo , Chen Yu-Xiang , Young Iris D. , Su Hong-Wei , Chen Yuemeng , Hong Jia-Yao , Fraser James S. , Javid Babak
Published: March 2021

Despite redundant cellular pathways to minimize translational errors, errors in protein synthesis are common. Pathways and mechanisms to minimize errors are classified as pre-ribosomal or ribosomal. Pre-ribosomal pathways are primarily concerned with the appropriate charging of tRNAs with their cognate amino acid. By contrast, the ribosomal decoding centre is considered ‘blind’ to mischarged tRNAs since these have cognate codon•anti-codon pairing. Here, we identified that in mycobacteria, deletion of the 16S ribosomal RNA methyltransferase gidB led to increased ribosomal discrimination of mischarged tRNAs. Discrimination only occurred in mycobacteria enriched from environments or genetic backgrounds with high rates of mistranslation. GidB deletion was necessary but not sufficient for reducing mistranslation due to misacylation. Analysis of new cryoEM structures of the M. smegmatis ribosomes derived from wild-type and gidB-deleted strains point to the interaction between the base methylated by GidB on the 16S RNA and an asparagine on the ribosomal S12 protein that when mistranslated to aspartate may be involved in altering translational fidelity. Our data suggest a mechanism by which mycobacterial ribosomes can discriminate mischarged tRNAs and that 16S rRNA differential methylation by GidB may act to prevent catastrophic translational error.
Targeting Biofilm of MDRProvidencia stuartiiby Phages Using a Catheter Model
Authors: Rakov Chani , Porat Shira Ben , Alkalay-Oren Sivan , Yerushalmy Ortal , Abdalrhman Mohanad , Gronovich Niv , Huang Lina , Pride David , Coppenhagen-Glazer Shunit , Nir-Paz Ran , Hazan Ronen
Published: March 2021

Providencia spp. are emerging pathogens mainly in nosocomial infections.Providencia stuartiiin particular is involved in urinary tract infections and contributes significantly to the high incidence of biofilm-formation in catheterized patients. Furthermore, recent reports suggested a role for multiple drug resistant (MDR)P. stuartiiin hospital-associated outbreaks which leads to excessive complications resulting in challenging treatments. Phage therapy is currently one of the most promising solutions to combat antibiotic-resistant infections. However, the number of available phages targetingProvidencia spp. is extremely limited, restricting the use of phage therapy in such cases. In the present study, we describe the isolation and characterization of 17 lytic and lysogenic bacteriophages targeting clinical isolates ofProvidencia spp. as part of the Israeli Phage Bank (IPB). These phages, isolated from sewage samples, were evaluated for host range activity and effectively eradicated 95% of the tested bacterial strains isolated from different geographic locations and displaying a wide range of antibiotic resistance. Their lytic activity is demonstrated on agar plates, planktonic cultures, and biofilm formed in a catheter model. The results suggest that these bacteriophages can potentially be used for treatment of antibiotic-resistantProvidencia spp. infections in general and of urinary tract infections in particular.
Upper respiratory tract SARS-CoV-2 RNA loads in symptomatic and asymptomatic children and adults
Authors: Costa Rosa , Bueno Felipe , Albert Eliseo , Torres Ignacio , Carbonell-Sahuquillo Silvia , Barrés-Fernández Ana , Sánchez David , Padrón Carmelo , Colomina Javier , Lázaro Carreño María Isabel , Bretón-Martínez José Rafael , Martínez-Costa Cecilia , Navarro David
Published: March 2021

Objectives

There is limited information comparing SARS-CoV-2 RNA load in the upper respiratory tract (URT) between children and adults, either presenting with COVID-19 or asymptomatic. Here we conducted a retrospective, single center study involving a large cohort of SARS-CoV-2 infected individuals to address this issue.

Patients and Methods

A total of 1,184 consecutive subjects (256 children and 928 adults) testing positive for SARS-COV-2 RNA in nasopharyngeal exudates (NP) were included, of whom 424 (121 children and 303 adults) had COVID-19 not requiring hospitalization and 760 (135 children and 625 adults) were asymptomatic close contacts of COVID-19 patients. SARS-CoV-2 RNA testing was carried out using the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, MS, USA). The AMPLIRUN® TOTAL SARS-CoV-2 RNA Control (Vircell SA, Granada, Spain) was used for estimating SARS-CoV-2 RNA loads (in copies/mL).

Results

Median SARS-COV-2 RNA loads were comparable between adults and children with COVID-19 (7.14 log10 copies/ml vs. 6.98 log10 copies/ml; P=0.094). Median SARS-CoV-2 RNA load in asymptomatic children and adults was similar (6.20 log10 copies/ml vs. 6.48 log10 copies/ml; P=0.97). Children with COVID-19 symptoms displayed SARS-CoV-2 RNA loads comparable to their asymptomatic counterparts (P=0.61). Meanwhile in adults, median SARS-CoV-2 RNA load was significantly higher in symptomatic than in asymptomatic subjects (P=<0.001), yet comparable (P=0.61) when the analysis excluded patients sampled within 48 h after symptoms onset.

Conclusions

The data suggest that children may be drivers of SARS-CoV-2 transmission in the general population at the same level as adults.
Heritage hotels and customer experience: a text mining analysis of online reviews
Authors: Chittiprolu Vinay , Samala Nagaraj , Bellamkonda Raja Shekhar
Published: March 2021

Purpose

In business, online reviews have an economic impact on firm performance. Customers’ data in the form of online reviews was used to understand the appreciation and service complaints written by previous customers. The study is an analysis of the online reviews written by the customers about Indian heritage hotels. This study aims to understand the dimensions of service appreciation and service complaints by comparing positive- and negative-rated reviews and find the patterns in the determinants of the satisfaction and dissatisfaction of the customers.

Design/methodology/approach

A total of 23,643 online reviews about heritage hotels were collected from the TripAdvisor website by using a Web crawler developed in Python. A total of 1000 reviews were randomly selected for further analysis to eliminate the bandwagon effect. Unsupervised text mining techniques were used to analyze reviews and find out the interesting patterns in text data.

Findings

Based on Herzberg two-factor theory, this study found satisfied and dissatisfied determinants separately. The study revealed some common categories discussed by satisfied and dissatisfied customers. The factors which satisfy the customers may also dissatisfy the customers if not delivered properly. Satisfied customers mentioned about tangible features of the hotel stay, which includes physical signifiers, traditional services, staff behavior and professionalism and core products (rooms, food). However, most of the customers complained about intangible service problems, such as staff attitude, services failure, issues with reservation and food, value for money and room condition. The results are contradicting with commercial hotels-based studies owing to the unique services provided by heritage hotels.

Practical implications

The dimensions for satisfaction and dissatisfaction among customer of heritage hotels provide marketers to understand the real emotion and perception of the customers. As these dimensions were extracted through text mining of the reviews written by the customer of heritage hotels, the results would certainly give better insights to the hotel marketers.

Originality/value

The study is a rare attempt to study online reviews of customers on heritage hotels through a text mining approach and find the patterns in the behavior and the determinants of satisfaction and dissatisfaction of customers.
“Exotic, welcoming and fresh”: stereotypes in new Nordic branding
Authors: Lerøy Sataøen Hogne
Published: March 2021

Purpose

Ideas related to “the Nordic” are important in the reconstruction of national identities in Denmark, Finland, Iceland, Norway and Sweden, and these countries’ modern national narratives are structurally highly similar. At the same time, there are clear differences between the Nordic countries regarding their national images. The purpose of this study is to a examine the relationship between ideas of the Nordic and national images through a qualitative study of brand manifestations on Nordic web portals for foreign visitors.

Design/methodology/approach

The two guiding research questions are: How do Nordic branding strategies and national stereotypes impact on nation-branding content toward visitors in the Nordic region? What traces of the Nordic as a supranational concept can be found when the Nordic is translated into concrete national brand manifestations? The analysis focuses on brand manifestations such as brand visions, codes of expression, differentiation, narrative identity and ideologies.

Findings

The analysis shows that clichés about the nations prevail in contemporary brand material and that Nordic branding strategies impact on the portals in diffuse and implicit ways. There are, however, some important common denominators, pointing toward a new Nordic brand related to exotic, untouched yet easily accessible nature, with a focus on pure, fresh and clean food with new tastes, in combination with happy and welcoming people.

Originality/value

The results from the study contribute with insight in how ideas of the Nordic on a supranational level transform when used in concrete and practical branding material. Further, this paper proposes a new Nordic branding focus, which contests traditional Nordic ideas.
The gains and pains of small and medium-scale enterprises (SMEs): the way forward for entrepreneurship development in Nigeria
Authors: Olaore Gbemi Oladipo , Adejare Bimbo Onaolapo , Udofia Ekpenyong Ekpenyong
Published: March 2021

Purpose

The purpose of this study is to assess the role of small and medium-scale enterprises (SMEs) as a catalyst to all things good in great economies; however, sadly, Nigeria has been unable to unlock SME development and the many benefits. The paper’s examination revolves around SMEs and entrepreneurial development, employment generation, government policies and financial aid and its availability. With the intention of establishing the relevance of government role in creating vibrant economies via thriving SMEs and its ripple effect on employment generation.

Design/methodology/approach

The study adopts a survey design, using a questionnaire for data gathering and percentile, confirmatory factor analysis (CFA) and structural equation modelling (SEM) for data analysis.

Findings

The study established a significant direct relationship between entrepreneurship development and infrastructure development and employment generation. Also, there was a significant direct relationship between government policies and infrastructure development. However, surprisingly, there was an insignificant relationship between government policy and financial aid and accessibility.

Practical implications

The government’s role in SMEs’ survival and entrepreneurship development is invaluable. The government must live up to their bidding and create an enabling environment to promote SME and entrepreneurship growth. Only this will transform the economy and minimize unemployment to its barest minimum.

Originality/value

The study’s research model is an interesting contribution to the body of work in SME and entrepreneurship development. The study is also an original attempt at having a good representation of the South-Western part of Nigeria, as research in high impact journals is usually domiciled in one state.
Modelling the comparative costs of Namaste Care: results from the namaste care intervention UK study
Authors: Bray Jennifer , Brooker Dawn , Latham Isabelle , Baines Darrin
Published: March 2021

Purpose

The purpose of this paper is to populate a theoretical cost model with real-world data, calculating staffing, resource and consumable costs of delivering Namaste Care Intervention UK (NCI-UK) sessions versus “usual care” for care home residents with advanced dementia.

Design/methodology/approach

Data from five care homes delivering NCI-UK sessions populated the cost model to generate session- and resident-level costs. Comparator usual care costs were calculated based on expert opinion and observational data. Outcome data for residents assessed the impact of NCI-UK sessions and aligned with the resident-level costs of NCI-UK.

Findings

NCI-UK had a positive impact on residents’ physical, social and emotional well-being. An average NCI-UK group session cost £220.53, 22% more than usual care, and ran for 1.5–2 h per day for 4–9 residents. No additional staff were employed to deliver NCI-UK, but staff-resident ratios were higher during Namaste Care. Usual care costs were calculated for the same time period when no group activity was organised. The average cost per resident, per NCI-UK session was £38.01, £7.24 more than usual care. In reality, costs were offset by consumables and resources being available from stock within a home.

Originality/value

Activity costs are rarely calculated as the focus tends to be on impact and outcomes. This paper shows that, although not cost neutral as previously thought, NCI-UK is a low-cost way of improving the lives of people living with advanced dementia in care homes.
Coral degradation impairs learning of non‐predators by Whitetail damselfish
Authors: Chivers Douglas P. , McCormick Mark I. , Fakan Eric P. , Edmiston Jake W. , Ferrari Maud C. O.
Published: March 2021

A prerequisite for effective antipredator responses is the ability of a prey to distinguish animals that pose a threat from those that do not. Prey often have efficient learning mechanisms to learn threats but learning to recognize nonpredators may be equally or more important. Moreover, the ability to generalize learned information is of key importance for prey animals. Prey take information they know about one species to make ‘educated guesses’ about the predatory/nonpredatory status of other unknown species.

Here, we investigate the ability of Whitetail damselfish Pomacentrus chrysurus to learn the identity of non‐predators and then generalize their responses to other unknown animals. Our work is completed within the context of unprecedented habitat degradation in reef ecosystems. When corals die, the remaining skeleton is colonized by algae, cyanobacteria and sessile invertebrates. These opportunistic colonists change the physical and chemical landscape of the reef and hence the background odour in which predator and non‐predator recognition occurs.

Our results indicated that Whitetail damselfish learn to classify Moonwrasse Thalasomma lunare as a non‐predator through the process of latent inhibition, whereby the prey are repeatedly exposed to Moonwrasse odour multiple times in the absence of negative reinforcement. These fish subsequently generalized their nonpredator recognition to other unknown wrasse, but not distantly related fish. Of key importance was our finding that the patterns and extent of non‐predator learning and generalization were dramatically altered in dead coral habitats. As predicted, prey that learned the Moonwrasse as a nonpredator in live coral environments did not subsequently respond to Moonwrasse when we tried to teach them Moonwrasse was a predator in live coral. However, this non‐predator recognition was reduced in dead coral environments. Moreover, generalization completely failed when we changed from live to dead coral environments.

Juvenile damselfishes need to rapidly catalogue the identity of unknown animals when they arrive at a reef. Changing background odours, that occur with changing tides and currents, means that prey need to learn non‐predator identities separately in each water source. This cognitive challenge likely has significant survival consequence in a changing environment.

A free Plain Language Summary can be found within the Supporting Information of this article.
Triennial migration and philopatry in the critically endangered soupfin shark Galeorhinus galeus
Authors: Nosal Andrew P. , Cartamil Daniel P. , Ammann Arnold J. , Bellquist Lyall F. , Ben‐Aderet Noah J. , Blincow Kayla M. , Burns Echelle S. , Chapman Eric D. , Freedman Ryan M. , Klimley A. Peter , Logan Ryan K. , Lowe Christopher G. , Semmens Brice X. , White Connor F. , Hastings Philip A.
Published: March 2021

Globally, one quarter of shark and ray species are threatened with extinction due to overfishing. Effective conservation and management can facilitate population recoveries. However, these efforts depend on robust data on movement patterns and stock structure, which are lacking for many threatened species, including the Critically Endangered soupfin shark Galeorhinus galeus, a circumglobal coastal‐pelagic species.

Using passive acoustic telemetry, we continuously tracked 34 mature female soupfin sharks, surgically implanted with coded acoustic transmitters, for 7 years via 337 underwater acoustic receivers stationed along the west coast of North America. These sharks and an additional six were also externally fitted with spaghetti identification tags. Our tagging site was a shallow rocky reef off La Jolla (San Diego County), California, USA, where adult females were observed to aggregate every summer.

Tagged soupfin sharks were highly migratory along the west coast of North America, between Washington, USA and Baja California Sur, Mexico. However, every 3 years, they returned to waters off La Jolla, California, where they underwent gestation. This is the first conclusive evidence of triennial migration and philopatry (‘home‐loving’) in any animal, which is apparently driven by this species’ unusual triennial reproductive cycle. Females of other shark and ray species with triennial reproductive cycles are also likely to exhibit triennial cycles of migration and philopatry.

At least six (15%) of our tagged soupfin sharks were killed in commercial gillnets in Mexico.

Policy implications. Identifying multiennial migratory cycles in mature female sharks can reveal hidden stock structure in the form of discrete breeding cohorts, which are spatially and temporally segregated as they cycle through different reproductive phases. Accounting for this complexity may improve the performance of spatially structured stock assessment models, particularly when fishery removals are spatially heterogeneous, as well as inform the spatiotemporal design of fishery‐independent surveys. In the United States, the soupfin shark is neither actively managed nor recognized as a Highly Migratory Species; however, given the highly migratory behaviour we report, this designation should be revisited by the US Pacific Fishery Management Council. Finally, given the extensive fishery removals in Mexico, any future management must be internationally cooperative.
Two‐months quality of life of COVID‐19 invasively ventilated survivors; an Italian single‐center study
Authors: Monti Giacomo , Leggieri Carlo , Fominskiy Evgeny , Scandroglio Anna Mara , Colombo Sergio , Tozzi Margherita , Moizo Elena , Mucci Milena , Crivellari Martina , Pieri Marina , Guzzo Francesca , Piemontese Simona , De Lorenzo Rebecca , Da Prat Valentina , Fedrizzi Monica , Faustini Carolina , Di Piazza Martina , Conte Francesca , Lembo Rosalba , Esposito Antonio , Dagna Lorenzo , Landoni Giovanni , Zangrillo Alberto
Published: March 2021

Background

COVID‐19 disease can lead to severe functional impairments after discharge. We assessed the quality of life of invasively ventilated COVID‐19 ARDS survivors.

Methods

We carried out a prospective follow‐up study of the patients admitted to the Intensive Care Units (ICUs) of a teaching hospital. Patients affected by COVID‐19 ARDS who required invasive ventilation and were successfully discharged home were assessed through the telephone administration of validated tests. We explored survival, functional outcomes, return to work, quality of life, cognitive and psychological sequelae. The main variables of interest were the following: demographics, severity scores, laboratory values, comorbidities, schooling, working status, treatments received during ICU stay, complications, and psychological, cognitive, functional outcomes.

Results

Out of 116 consecutive invasively ventilated patients, overall survival was 65/116 (56%) with no death occurring after hospital discharge. Forty‐two patients were already discharged home with a median follow‐up time of 61 (51‐71) days after ICU discharge and 39 of them accepted to be interviewed. Only one patient (1/39) experienced cognitive decline. The vast majority of patients reported no difficulty in walking (32/35:82%), self‐care (33/39:85%), and usual activities (30/39:78%). All patients were either malnourished (15/39:38%) or at risk for malnutrition (24/39:62%). Exertional dyspnea was present in 20/39 (51%) patients. 19/39 (49%) reported alterations in senses of smell and/or taste either before or after hospitalization.

Conclusions

Invasively ventilated COVID‐19 ARDS survivors have an overall good recovery at a 2‐months follow‐up which is better than what was previously reported in non‐COVID‐19 ARDS patients.
The views, experiences and expectations of Australian Meals on Wheels customers: A national survey
Authors: Coenen Alison , Clancy Annabel , Charlton Karen E. , McMahon Anne‐Therese , Ringland Emma , Williams Peter , Tapsell Linda C. , Walton Karen
Published: March 2021

Objective

To investigate views and expectations of Australian Meals on Wheels (MOW) customers to inform the development of National Meal Guidelines and improve current services.

Methods

A survey was designed through literature review and consultations with key stakeholders. National convenience sampling returned  337 surveys. Descriptive statistics and chi‐squared analyses were applied to the survey data.

Results

Meals on Wheels customers reported satisfaction with their current service, with the meal itself found to be the most valuable aspect. People living in small country towns were more likely to value the social contact provided by MOW than those in major cities (P = .001). Delivery of pantry items was the most popular additional option for future services.

Conclusion

Valuable information for inclusion in the development of the National Meal Guidelines was provided: nutritional content of meals, meal variety, packaging and presentation, opportunities for nourishing snacks and pantry items, and social contact.
Management of lateral pelvic lymph nodes by Australasian colorectal surgeons: An insight from the west
Authors: Cribb Benjamin , Kong Joseph , Warrier Satish , McCormick Jacob , Heriot Alexander
Published: March 2021

Purpose

Lateral pelvic lymph node dissection (LPLND) for locally advanced low rectal cancer is a common practice in Japan. However, it is not widely performed in western countries. The aim of this survey study is to assess the current practice and management of lateral pelvic lymph nodes by colorectal surgeons in Australasia.

Methods

The authors developed a survey to assess surgeons’ assessment and management of lateral pelvic lymph nodes in patients with rectal cancer. The survey was run through the online RedCap® platform in 2019. An electronic link and request to complete the survey was sent to specialist surgeons of the Colorectal Surgical Society of Australia and New Zealand (CSSANZ).

Results

Ninety‐two colorectal surgeons completed the online survey (32% response rate). Eighty percent of participants consider malignant lateral pelvic lymph nodes to represent locoregional and resectable disease. In patients with clinically malignant lateral pelvic lymph nodes on preoperative imaging the majority of respondents (92%) recommend neoadjuvant chemoradiotherapy and 86% would also recommend LPLND. Over half of the surgeons (57%) had no exposure to LPLND during fellowship training and approximately two thirds (62%) do not perform LPLND in their current practice.

Conclusion

This study highlights the challenges in the management of the lateral pelvic lymph nodes in a western context. The majority of the participating Australasian colorectal surgeons consider malignant lateral pelvic lymph nodes to represent locoregional and resectable disease. The majority also recommend LPLND for clinically malignant lateral pelvic nodes. However, adequate training and experience with LPLND is limited.
Low androgen status inhibits erectile function by increasing pyroptosis in rat corpus cavernosum
Authors: Chen Zhi‐bin , Li Ge , Lin Haocheng , Jiang Jun , Jiang Rui
Published: March 2021

Background

The mechanism of erectile dysfunction (ED) caused by low androgen status is not fully understood.

Objectives

To investigate whether low androgen status inhibits erectile function of rats by inducing pyroptosis in the corpus cavernosum (CC).

Materials and methods

Thirty‐six eight‐weeks‐old healthy male Sprague‐Dawley rats were equally divided into six groups: sham‐operated group (4w sham, 8w sham), castration group (4w cast, 8w cast), and castration + testosterone (T) group (4w cast + T, 8w cast + T). The rats in castration + T groups were injected with testosterone propionate subcutaneously every other day. After 4 and 8 weeks, the ratio of maximum intracavernous pressure (ICPmax)/mean arterial pressure (MAP), the level of serum T, the concentration of nitric oxide (NO) and interleukin‐1β (IL‐1β), the expression of NOD‐like receptor pyrin domain containing 3 (NLRP3), apoptosis‐associated speck‐like protein containing a caspase activation and recruitment domain (ASC), Caspase‐1 p20, gasdermin D‐N (GSDMD‐N), transforming growth factor β1 (TGF‐β1), collagen‐I, and collagen‐III, the ratio of smooth muscle/collagen (SM/C), and the proportion of pyroptotic cells in the CC were analyzed.

Results

The ratio of ICPmax/MAP (3/5 V) and SM/C, the level of NO and serum T was significantly decreased in castration groups when compared to other groups (p < 0.01). NLRP3, ASC, Caspase‐1, and GSDMD were mainly expressed in the cytoplasm of smooth muscle cells (SMCs) and endothelial cells (ECs) in the CC. The expression of NLRP3, ASC, Caspase‐1p20, GSDMD‐N, IL‐1β, TGF‐β1, collagen‐I, and collagen‐III was significantly increased in castration groups when compared with other groups (p < 0.01). The proportion of pyroptotic cells in the CC was increased significantly in castration groups when compared with other groups (p < 0.05).

Discussion and Conclusion

Low androgen status inhibits erectile function of rats by promoting CC fibrosis and reducing NO synthesis through pyroptosis of SMCs and ECs in the CC.
Efficacy of multidisciplinary team approach with extracorporeal membrane oxygenation for COVID‐19 in a low volume ECMO center
Authors: Nagaoka Eiki , Arai Hirokuni , Ugawa Toyomu , Masuda Takahiro , Ochiai Kanae , Tamaoka Meiyo , Kurashima Naoki , Oi Keiji , Fujiwara Tatsuki , Yoshida Masayuki , Shigemitsu Hidenobu , Otomo Yasuhiro
Published: March 2021

Veno‐venous extracorporeal membrane oxygenation (VV ECMO) is an effective and proven adjunct support for various severe respiratory failures requiring invasive mechanical ventilation and cardiovascular support. In response to the rapidly increasing number of COVID‐19 patients in Japan, we launched an ECMO support team comprised of multidisciplinary experts including physicians, nurses, perfusionists, and bioethicists in preparation for the threat of a pandemic. From April 2 to July 15, 2020, Tokyo Medical and Dental University hospital treated 104 PCR confirmed COVID‐19 patients. Among those, 34 patients were admitted to intensive care unit (ICU) and 5 patients required VV ECMO. All management related to ECMO was decided by the ECMO support team in addition to participation of the ECMO support team in daily multidisciplinary rounds in the ICU. Median age was 54 years old. Duration from onset to mechanical ventilation (MV) and MV to ECMO were 8 and 7 days, respectively. Four patients (80%) were successfully weaned off from ECMO. One patient died after 81 days of ECMO run. Four patients were discharged and recovered to their prehospital quality of life without major disability. We achieved a high survival rate using ECMO in our low volume ECMO institution during the COVID‐19 pandemic. Multidisciplinary decision‐making and a team approach for the unclear pathology with an emerging infectious disease was effective and contributed to the survival rate.
Effects of the co‐administration of MK‐801 and clozapine on MiRNA expression profiles in rats
Authors: Huang Wenhui , Gu Xuefeng , Wang Yingying , Bi Yuhan , Yang Yu , Wan Guoqing , Chen Nianhong , Li Keshen
Published: March 2021

MiRNAs are small, non‐coding RNAs that can silence the expression of various target genes by binding their mRNAs and thus regulate a wide range of crucial bodily functions. However, the miRNA expression profile of schizophrenia after antipsychotic mediation is largely unknown. Non‐competitive N‐methyl‐D‐aspartic acid (NMDA) receptor antagonists such as MK‐801 have provided useful animal models to investigate the effects of schizophrenia‐like symptoms in rodent animals. Herein, the hippocampal miRNA expression profiles of Sprague‐Dawley rats pretreated with MK‐801 were examined after antipsychotic clozapine (CLO) treatment. Total hippocampal RNAs from three groups were subjected to next‐generation sequencing (NGS), and bioinformatics analyses, including differential expression and enrichment analyses, were performed. Eight miRNAs were differentially expressed between the MK‐801 and vehicle (VEH) control groups. Interestingly, 14 miRNAs were significantly differentially expressed between the CLO + MK‐801 and MK‐801 groups, among which rno‐miR‐184 was the most upregulated. Further analyses suggested that these miRNAs modulate target genes that are involved in endocytosis regulation, ubiquitin‐mediated proteolysis, and actin cytoskeleton regulation and thus might play important roles in the pathogenesis of schizophrenia. Our results suggest that differentially expressed miRNAs play important roles in the complex pathophysiology of schizophrenia and subsequently impact brain functions.
Contact allergy and allergic contact dermatitis from benzalkonium chloride in a tertiary dermatology center in Melbourne, Australia
Authors: Dear Kate , Palmer Amanda , Nixon Rosemary
Published: March 2021

Background

Benzalkonium chloride (BAK) is a quaternary ammonium compound that is used widely as an antiseptic and preservative. It is a strong irritant and considered a weak sensitizer.

Objective

To analyze the temporal trend of BAK sensitization and the demographics of sensitized patients.

Methods

We conducted a single‐center retrospective study of 7390 patients who were patch tested with BAK between January 1, 2003 and December 31, 2019.

Results

Of the 7390 patients who were patch tested to BAK, 108 (1.5%) had a positive reaction, with 21 reactions deemed clinically relevant (0.3% of total patch tested) and a further 5 doubtful reactions deemed clinically relevant, resulting in a total of 26 relevant reactions (0.4% of total patch tested). Common sources of exposure were ophthalmic drops (30.8%), topical antiseptic preparations (26.9%), cosmetics (15.4%), disinfectant solutions (11.5%), hand sanitizers (11.5%), and hand washes (7.7%). One fifth of patients with relevant reactions were health care workers. There has been a dramatic increase in the number of positive reactions since 2017, for reasons not totally clear.

Conclusion

Contact allergy (CA) and allergic contact dermatitis (ACD) in response to BAK are now increasing at our center. Awareness of this trend is important, given that the coronavirus disease 2019 (COVID‐19) pandemic is likely to further expose people to BAK.
An Exploration and Critical Examination of How “Intelligent Classroom Technologies” Can Improve Specific Uses of Direct Student Behavior Observation Methods
Authors: Woolverton Genevieve Alice , Pollastri Alisha R.
Published: March 2021

Within classrooms, psychologists and teachers use direct behavior observation methods, systematic behavior observations (SBOs) and direct behavior ratings (DBRs), to gather information about students' behaviors for the purposes of making decisions related to diagnosis and classroom management or behavioral feedback respectively. Observers use SBOs to document predetermined target behaviors exhibited by one or a few target students with standardized parameters. Teachers use DBRs to track and manage their students' behaviors, most frequently recording data on all of their students' desirable and undesirable behavior throughout class while teaching. While SBOs and DBRs are ecologically valid, they are limited by observers' attentional limits and implicit biases, and DBRs are uniquely limited by teacher resources as they balance teaching with recording behavioral data about many students. Intelligent classroom technologies collect a high volume of data with object reliance on algorithms as opposed to observational judgment, which makes them well suited to address limitations specifically associated with the use of data derived from DBRs. Intelligent classroom technologies include eye gaze tracking methods that document students' visual fixations and wearable or within‐desk devices that monitor students' movements and/or vocalizations. These devices have the potential to record myriad behaviors of interest and transmit data in vivo for immediate responses from teachers with high efficiency and reduced reliance on human judgment and error. However, they may be associated with ethnical and/or privacy issues, which are discussed along with suggestions for addressing these challenges.
Acute corneal hydrops of presumed traumatic origin: An uncontrolled case series (three horses)
Authors: O’Leary L. M. , Sebbag L. , Moody L. M. , Diehl K. A. , Allbaugh R. A.
Published: March 2021

This case series describes acute corneal hydrops in three young horses. Due to similarities in the clinical appearance and progression of the disease with that which is reported in humans and cats with acute corneal hydrops, traumatic Descemet’s membrane rupture was suspected to be the underlying aetiology in these equine cases. The horses presented with acute severe corneal oedema with intrastromal bullae formation and anterior bulging of the corneal contour. Focal posterior corneal changes were also seen in two of three cases. Mild anterior uveitis was also present. Other causes of corneal oedema (e.g. glaucoma) were ruled out based on presentation and clinical examination. Treatment approaches were medical and included various combinations of prophylactic topical antimicrobial therapy in case of secondary corneal ulceration, anti‐inflammatory therapy for uveitis, targeted oedema therapy with topical hypertonic saline and corneal cross‐linking, and placement of a temporary partial tarsorrhaphy for corneal tamponade. The outcome was excellent in all cases, with rapid resolution of the ocular changes. Acute corneal hydrops of presumed traumatic Descemet’s membrane rupture origin should be considered in cases of young horses presenting with acute corneal oedema. However, further studies are warranted to better characterise the disease and to try to confirm the suspected aetiology.
Whole‐slide margin control through deep learning in Mohs micrographic surgery for basal cell carcinoma
Authors: van Zon Mike C.M. , van der Waa José D. , Veta Mitko , Krekels Gertruud A.M.
Published: March 2021

Background

Basal cell carcinoma (BCC) is the most common type of skin cancer with incidence rates rising each year. Mohs micrographic surgery (MMS) is most often chosen as treatment for BCC on the face for which each frozen section has to be histologically analysed to ensure complete tumor removal. This causes a heavy burden on health economics.

Objectives

To develop and evaluate a deep learning model for the automated detection of BCC‐negative slides and classification of BCC in histopathology slides of MMS based on whole‐slide image (WSI).

Methods

Two deep learning models were developed on the basis of 171 digitized H&E frozen slides from 70 different patients. The first model had a U‐Net architecture and was used for the segmentation of BCC. A subsequent convolutional neural network used the segmentation to classify the whole slide as BCC or BCC‐negative.

Results

Quantitative evaluation over manually labelled ground truth data resulted in a Dice score of 0.66 for the segmentation of BCC and an area under the receiver operating characteristic curve (AUC) of 0.90 for the slide‐level classification.

Conclusions

This study demonstrates that through WSIs deep learning models may be a feasible option to improve the clinical workflow and reduce costs in histological analysis of BCC in MMS.
Importance of extracutaneous organ involvement in determining the clinical severity and prognosis of incontinentia pigmenti caused by mutations in the IKBKG gene
Authors: Kim Hwa Young , Song Hyun Beom , Kim Kyu Han , Kim Jeong Hun , Chae Jong‐Hee , Kim Man Jin , Seong Moon‐Woo , Ko Jung Min
Published: March 2021

Incontinentia pigmenti (IP) is a rare X‐linked skin disease caused by mutations in the IKBKG gene, which is required for activation of the nuclear factor‐kappa B signalling pathway. Multiple systems can be affected with highly variable phenotypic expressivity. We aimed to clarify the clinical characteristics observed in molecularly confirmed Korean IP patients. The medical records of 25 females confirmed as IP by molecular genetic analysis were retrospectively reviewed. The phenotypic score of extracutaneous manifestations was calculated to assess the disease severity. The IKBKG gene partial deletion or intragenic mutations were investigated using long‐range PCR, multiplex ligation‐dependent probe amplification and direct sequencing methods. Among the 25 individuals, 18 (72%) were sporadic cases. All patients showed typical skin manifestations at birth or during the neonatal period. Extracutaneous findings were noted in 17 (68%) patients; ocular manifestations (28%), neurological abnormalities (28%), hair abnormalities (20%), dental anomalies (12%), nail dystrophy (8%). The common exon 4–10 IKBKG deletion was observed in 20 (80%) patients. In addition, five intragenic sequence variants were identified, including three novel variants. The phenotype scores were highly variable, ranging from abnormal skin pigmentation only to one or more extracutaneous features, although no significant difference was observed for each clinical characteristic between the group with sequence variants and that with common large deletion. Our cohort with IP showed heterogeneity of extracutaneous manifestations and high incidence of sporadic cases. Long‐term monitoring with multidisciplinary management is essential for evaluating the clinical status, providing adequate genetic counselling and understanding the genotype‐phenotype correlation in IP.
Helicobacter pylori knowledge and perception among multi‐ethnic Asians
Authors: Teng Thomas Zheng Jie , Sudharsan Madhavan , Yau Joachim Wen Kien , Tan Weiting , Shelat Vishalkumar G.
Published: March 2021

Background

Helicobacter pylori (HP) infection is endemic and causes peptic ulcer disease and gastric cancer. There is a lack of data related to awareness of the general public about HP and associated health risks. The objective of this study was to investigate the awareness and public perceptions about HP and the attitudes towards screening.

Methods

This cross‐sectional study included a structured 19‐item questionnaire targeting members of the general public at a restructured acute hospital in Singapore.

Results

Out of 504 participants, 152 (30.2%) were aware of HP. Higher education was associated with HP awareness (p < 0.001, OR 7.4, 95% CI 1.6–32.6). A third, 175 (34.7%) of the respondents identified the stomach as the primary site of infection. 131 (26.0%) respondents identified the fecal‐oral route as a mode of transmission. 178 (35.3%) respondents were aware of available screening modalities, with around half of them willing to be screened with blood (n = 256, 50.8%) or breath tests (n = 265, 52.6%). 430 (85.3%) participants were keen to learn more about HP, and this was associated with age (p < 0.05, OR 3.9, 95% CI 2.1–7.1).

Conclusion

Awareness about HP infection is low, and acceptance of screening tests is high. Educational efforts are needed to improve awareness.
Effects of patient decision aids in patients with type 2 diabetes mellitus: A systematic review and meta‐analysis
Authors: Li Zimeng , Jin Yinghui , Lu Cui , Luo Ruzhen , Wang Jiayao , Liu Yanhui
Published: March 2021

Aims

This study aimed to systematically evaluate the effectiveness of patient decision aids on knowledge, decisional conflict and decisional self‐efficacy outcomes in patients with diabetes.

Methods

A comprehensive database search was performed using the Web of Science, Cochrane Library, PubMed, Embase, PsycINFO (Ovid), CINAHL (EBASCO), CNKI, VIP, Wan Fang Database and the Ottawa Decision Aid Library Inventory (http://decisionaid.ohri.ca/index.html) from inception to 13 October 2019. Two reviewers independently searched databases, screened articles, extracted data and evaluated the risk bias of included studies. Then Rev Man 5.3 software was adopted for statistical analysis.

Results

Ten articles containing 1,452 people with diabetes were selected. The results of meta‐analysis showed that patient decision aids had a positive effect on reducing decisional conflict and improving decisional self‐efficacy among patients with type 2 diabetes. Meanwhile, this article also revealed that patient decision aids have beneficial short‐term effects on improving knowledge, but there was no significant long‐term effect.

Conclusion

Patient decision aids are capable of becoming support tools to improve shared decision making. Further implementation studies are required to transform patient decision aids tools into clinical practice.