bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of an Acupressure Training Program for Pediatric Nurses Caring for Children Undergoing Chemotherapy
Authors: Mohammed Hanaa Gaber , Al-Sharkawi Sabah Saad , Mohammed Adly Randa
Published: December 2022

Acupressure is a nonpharmacological technique that can be used to control chemotherapy-induced nausea and vomiting (CINV) in children with cancer. To use acupressure as a strategy for managing CINV, oncology nurses must have adequate knowledge and skills to implement the technique in clinical practice. Our study aimed to evaluate the effect of an acupressure training program for pediatric nurses caring for children undergoing chemotherapy. We used a quasi-experimental design. Our sample populations included a convenience sample of 36 pediatric nurses and a purposive sample of 45 children undergoing chemotherapy. We used four tools for data collection: (1) a structured questionnaire comprising two parts: (a) characteristics of nurses and children and (b) assessment of nurses' knowledge; (2) an observational checklist for application of acupressure technique; (3) the Baxter Animated Retching Faces (BARF) scale; and (4) a vomiting assessment sheet. We found that after the training intervention, 94.4% (n = 34) of nurses had a good level of knowledge and skill implementing the acupressure technique. There was a statistically significant difference in the knowledge and skill of the nurses before and after the training intervention, χ2(35, N = 36) = 19.113, p = .000. We concluded that the training program significantly improved the nurses' level of knowledge and skill when caring for children undergoing chemotherapy. We also found that after implementing the training intervention, the frequency and severity of CINV decreased among the children we studied. We therefore recommend that acupressure (in combination with antiemetic medication) be included as part of a protocol for chemotherapy administration in children.
Comparative Efficacy of Intralesional Triamcinolone Acetonide and 5-Fluorouracil for Keloid Scars [RETRACTED]
Authors: Kaur Amandeep , Garg Ramneesh , Mittal Rajinder K. , Shah Sheerin , Patial Tushar , Addiwal Raman
Published: December 2022

Intralesional triamcinolone acetonide (TAC; a synthetic corticosteroid) and 5-fluorouracil (5-FU; a cytotoxic chemotherapy drug) are the medications most commonly used to treat keloid scars. We investigated the clinical efficacy of TAC compared with 5-FU. We included 40 patients in the study and divided them into two equal groups (n = 20 Group A; n = 20 Group B). Group A patients received 4 mg/cm2 or 0.1 ml/cm2 of intralesional TAC (40 mg/ml) at 3-week intervals. Group B patients received 10 mg/cm2 or 0.2 ml/cm2 of intralesional 5-FU (50 mg/ml) at 3-week intervals. We assessed the scar using the Vancouver Scar Scale (VSS), visual analog scale (VAS), and patient satisfaction score (PSS). We found that Group A patients had a lower VAS than Group B patients (2.09 vs. 3.18). We saw a reduction in the VSS in both treatment arms; however, we found that Group B patients had a more marked reduction in the VSS compared with Group A patients (2.57 vs. 2.68). The PSS was higher in Group A than in Group B (1.97 vs. 1.78). We concluded that intralesional 5-FU elicits a better response than intralesional TAC. Although 5-FU is less well tolerated and has more side effects than TAC, we found that 5-FU was more effective in resolving keloid scars. Notably, the PSS was higher in the TAC group, but the VSS and VAS were better in Group B.
PET/CT Showing a Case of Langerhans Cell Histiocytosis Involving the Pleura
Authors: Tang Pan , Zhou Yushan , Tian Rong
Published: December 2022

We describe a case of Langerhans cell histiocytosis involving the bilateral pleura on FDG PET/CT. Multiple pleural nodules were detected by CT in a 38-year-old woman with chest pain and night sweats. Malignant tumors were suspected. PET/CT showed abnormal FDG uptake in those pleural lesions. No other abnormal foci were seen in the rest of the whole body. A primary pleural disease was considered. Then the histopathologic findings after biopsy confirmed the diagnosis of Langerhans cell histiocytosis.
68Ga-DOTANOC PET/CT in Adrenal Schwannoma
Authors: Aggarwal Piyush , Singh Harmandeep , Kumar Rajender , Nada Ritambhra , Bora Girdhar S. , Walia Rama
Published: December 2022

Adrenal schwannoma is a rare adrenal incidentaloma. It is a benign tumor arising from the Schwann cells. Differentiating benign from malignant adrenal lesions requires a combination of clinical, biochemical, imaging, and histopathological findings. 68Ga-DOTANOC PET/CT is one of the sensitive imaging modalities to detect adrenal lesions such as pheochromocytoma. Multiple benign and malignant lesions show somatostatin receptor expression causing a high probability of false-positive findings on somatostatin receptor imaging. We present a case of adrenal incidentaloma positive on 68Ga-DOTANOC PET, which revealed a benign adrenal spindle cell tumor on histopathology.
Metastatic Papillary Thyroid Cancer Mimicking Hypopharyngeal Carcinoma
Authors: Du Bulin , Wang Shu , Liu Yi , Li Yaming , Li Xuena
Published: December 2022

Papillary thyroid cancer (PTC) metastasizing to the hypopharynx is extremely rare. Here, we describe FDG PET/CT findings of lesions in the posterior hypopharyngeal wall and left parapharyngeal space in a 58-year-old man who complained of blood in the sputum. The patient had a history of postoperative PTC. Therefore, hypopharyngeal carcinoma with lymph node metastasis was suspected. However, metastasis of PTC was pathologically confirmed after surgery. Hypopharyngeal metastasis of PTC is rare, which should be differentiated from hypopharyngeal carcinoma with metastasis.
Is a Defunctioning Stoma Necessary After Left Colectomy in High-risk Patients for Anastomotic Leak?
Authors: Bouland Tressy , Sabbagh Charles , Allart K Kevin , Pellegrin Alexandra , Regimbeau Jean-Marc
Published: December 2022

Introduction:

Left colectomy is associated with a 7% risk of anastomotic leak. In 2011, a prediction score for AL [the colon leakage score (CLS)] was developed. The aim was to evaluate the impact of a defunctioning stoma on AL and its consequences after left colectomy in high-risk patients.

Patients:

From January 2012 to June 2019, high-risk patients who underwent a left colectomy with anastomosis were included in this retrospective, single-center study. Two groups of patients were defined: patients undergoing a left colectomy with an anastomosis without a defunctioning stoma (no-stoma group) and those with a defunctioning stoma (stoma group). The primary endpoint was the rate of anastomotic leakage.

Results:

Ninety-two patients were included in this study. The anastomotic leakage rate was 16.4% in the no-stoma group and 21.6% in the stoma group (P=0.5). A conservative approach was applied to 11.2% in the no-stoma group and 50% in the stoma group (P=0.1). The severe morbidity rate was 14.5% in the no-stoma group and 21.6% in the stoma group (P=0.4). The rate of unplanned admissions was 7% in the no-stoma group and 27% in the stoma group (P=0.01).

Conclusion:

A defunctioning stoma does not appear to reduce the rate of AL in high-risk patients, but its impact on the management of AL remains unclear.
Assessing the Educational Value of YouTube Videos on Major Laparoscopic Liver Resection: A Cross-sectional Study of the Top 20 Most Viewed Laparoscopic Right and Left Hepatectomy Videos
Authors: Goh Nathanael , Chan Kai Siang , Teng Thomas Zheng Jie , Shelat Vishal G.
Published: December 2022

Background:

Surgical videos uploaded on social media platforms like YouTube augment the learning experience of advanced procedures like major laparoscopic liver resection (LLR). However, because of the heterogeneous quality, the educational value of such videos is unproven. This study assesses the educational value of YouTube’s top 20 most viewed major LLR videos.

Materials and Methods:

The search terms “laparoscopic hemihepatectomy,” “laparoscopic right hepatectomy,” and “laparoscopic left hepatectomy” were searched on YouTube on October 7, 2020. Exclusion criteria were minor hepatectomy, open hepatectomy, live donor right and left hepatectomy, robotic hepatectomy videos, and nonstandard laparoscopic technique. Videos were graded based on adherence to key steps in LLR and compliance to the modified LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS); 29 of the original 37 consensus statements were used in our study.

Results:

The videos have a median of 7647 views (range: 2675 to 67,449), a median of 34 likes (range: 3 to 67), and a median of 1 dislike (range: 0 to 22). The median duration of major LLR videos was 11.0 minutes (range: 6.38 to 223 min). Majority of the videos had duration of <30 minutes (n=18/20, 90%). There were 14 videos (70%) demonstrating all defined surgical steps. The liver mobilization was shown in 17 videos (75%). Vascular inflow control of hepatic artery and portal vein and vascular outflow control were demonstrated in 18 videos (90%). Parenchymal transection and hemostasis were shown in all videos. The median LAP-VEGaS score across all 20 videos is 6 (range: 1 to 11) out of 29, translating to a median score of 20.6% (range: 3.4% to 37.9%). Thirteen out of 29 of the LAP-VEGaS criteria graded (44.8%) were not met by any of the 20 videos.

Conclusions:

The top 20 most viewed surgical videos on laparoscopic right and left hepatectomy may not be the ideal material for the educational value of surgical trainees. The LAP-VEGaS guidelines are too exhaustive for relevance to social media platforms as an educational tool.
Isolated Appendectomy Technique Without Mesoappendix in Laparoscopic Appendectomy
Authors: Tazeoglu Deniz , Esmer Ahmet C. , Benli Sami
Published: December 2022

Background:

Laparoscopic appendectomy is among the most common general surgical procedures performed in developed countries. Among the most critical steps in laparoscopic appendectomy is transection of the appendix meso. This study evaluates the postoperative and economic outcomes between total mesoicular excision and isolated (traditional) appendectomy technique during appendix transsection, in line with the patients’ clinicopathologic data.

Materials and Methods:

Patients who were operated on with the diagnosis of acute appendicits in our clinic between October 2021 and January 2022 were evaluated retrospectively. Patients were divided into 2 groups. In the first group, there is the isolated appendectomy technique in which the appendix meso is dissection from the tip of the appendix to the base of the cecum, while in the second group there is the technique in which the appendix meso is dissected from the base of the cecum. In addition, demographic data (age, sex), body mass index, presence of comorbid disease, operation time, postoperative hospital stay, health care costs, appendix size of the patients included in the study were recorded.

Result:

During the study, 157 patients were included in the study. Seventy-one (45.2%) of the patients were in group 1, and 86 (54.8%) were in group 2. There was no difference between the groups regarding age, sex, body mass index, presence of comorbid disease, appendix size, and postoperative hospital stay (P>0.05). However, operation time and health care costs were statistically higher in group 2 than in group 1 (P=0.01).

Conclusion:

Although there was no difference in postoperative complications between the isolated appendectomy technique and the mesoicular technique, the operation time was shorter, and the operation cost was lower in the isolated appendectomy technique.
Is Endoscopic Submucosal Dissection for Colorectal Lesions Performed in the Endoscopy Suite Safe and Cost Saving?
Authors: Tatar Cihad , Ozgur Ilker , Justiniano Carla F. , Bhatt Amit , Liska David , Hull Tracy , Steele Scott R. , Gorgun Emre
Published: December 2022

Background:

We aimed to compare the outcomes and the cost differences of endoscopic submucosal dissection (ESD) procedures in the endoscopy suite (ES) versus the operating room (OR).

Materials and Methods:

The procedures in the OR were compared with procedures performed in the ES for demographics, lesion characteristics, procedure outcome, and procedure charges. The study included 163 procedures in the ES and 73 in the OR.

Results:

Both were similar in age, sex, body mass index, and intraprocedural and postoperative 30-day (late) complications. ES cases had significantly greater polyp size, were more commonly right-sided polyps, and had shorter hospital stays, with similar en bloc and margin-negative resection rates. The overall cost ratio of ESD procedures in ES to OR was 0.47 (P<0.001).

Conclusions:

Colorectal ESD procedures performed in the ES have similar efficacy and safety as those in the OR. Procedures performed in the ES were associated with a shorter length of stay and significant periprocedural cost savings.
Characterization of Pantoea ananatis from rice planthoppers reveals a clade of rice-associated P. ananatis undergoing genome reduction
Authors: Bing Xiao-Li , Wan Yu-Ying , Liu Huan-Huan , Ji Rui , Zhao Dian-Shu , Niu Yue-Di , Li Tong-Pu , Hong Xiao-Yue
Published: December 2022

Pantoea ananatis

is a bacterium that is found in many agronomic crops and agricultural pests. Here, we isolated a

P. ananatis

strain (Lstr) from the rice planthopper Laodelphax striatellus, a notorious pest that feeds on rice plant sap and transmits rice viruses, in order to examine its genome and biology.

P. ananatis

Lstr is an insect symbiont that is pathogenic to the host insect and appears to mostly inhabit the gut. Its pathogenicity thus raises the possibility of using the Lstr strain as a biological agent. To this end, we analysed the genome of the Lstr strain and compared it with the genomes of other

Pantoea

species. Our analysis of these genomes shows that

P. ananatis

can be divided into two mono-phylogenetic clades (clades one and two). The Lstr strain belongs to clade two and is grouped with

P. ananatis

strains that were isolated from rice or rice-associated samples. A comparative genomic analysis shows that clade two differs from clade one in many genomic characteristics including genome structures, mobile elements, and categories of coding proteins. The genomes of clade two

P

.

ananatis

are significantly smaller, have much fewer coding sequences but more pseudogenes than those of clade one, suggesting that clade two species are at the early stage of genome reduction. On the other hand,

P. ananatis

has a type VI secretion system that is highly variable but cannot be separated by clades. These results clarify our understanding of

P. ananatis

’ phylogenetic diversity and provide clues to the interactions between

P. ananatis

, host insect, and plant that may lead to advances in rice protection and pest control.
Characterization of a P1-bacteriophage-like plasmid (phage-plasmid) harbouring bla
CTX-M-15 in Salmonella enterica serovar Typhi
Authors: Greig David R. , Bird Matthew T. , Chattaway Marie Anne , Langridge Gemma C. , Waters Emma V. , Ribeca Paolo , Jenkins Claire , Nair Satheesh
Published: December 2022

Antimicrobial-resistance (AMR) genes can be transferred between microbial cells via horizontal gene transfer (HGT), which involves mobile and integrative elements such as plasmids, bacteriophages, transposons, integrons and pathogenicity islands. Bacteriophages are found in abundance in the microbial world, but their role in virulence and AMR has not fully been elucidated in the

Enterobacterales

. With short-read sequencing paving the way to systematic high-throughput AMR gene detection, long-read sequencing technologies now enable us to establish how such genes are structurally connected into meaningful genomic units, raising questions about how they might cooperate to achieve their biological function. Here, we describe a novel ~98 kbp circular P1-bacteriophage-like plasmid termed ph681355 isolated from a clinical

Salmonella enterica

serovar Typhi isolate. It carries bla
CTX-M-15, an IncY plasmid replicon (repY gene) and the ISEcP1 mobile element and is, to our knowledge, the first reported P1-bacteriophage-like plasmid (phage-plasmid) in

S

.

enterica

Typhi. We compared ph681355 to two previously described phage-plasmids, pSJ46 from

S

.

enterica

serovar Indiana and pMCR-1-P3 from

Escherichia coli

, and found high nucleotide similarity across the backbone. However, we saw low ph681355 backbone similarity to plasmid p60006 associated with the extensively drug-resistant

S

.

enterica

Typhi outbreak isolate in Pakistan, providing evidence of an alternative route for bla
CTX-M-15 transmission. Our discovery highlights the importance of utilizing long-read sequencing in interrogating bacterial genomic architecture to fully understand AMR mechanisms and their clinical relevance. It also raises questions regarding how widespread bacteriophage-mediated HGT might be, suggesting that the resulting genomic plasticity might be higher than previously thought.
Bayesian Spatio-temporal prediction and counterfactual generation: an application in non-pharmaceutical interventions in Covid-19
Authors: Lawson Andrew , Rotejanaprasert Chawarat
Published: December 2022

The spatio-temporal course of an epidemic (such as Covid-19) can be significantly affected by non-pharmaceutical interventions (NPIs), such as full or partial lockdowns. Bayesian Susceptible-Infected-Removed (SIR) models can be applied to the spatio-temporal spread of infectious disease (STIF) (such as Covid-19). In causal inference it is classically of interest to investigate counterfactuals. In the context of STIF it is possible to use nowcasting to assess the possible counterfactual realization of disease in incidence that would have been evidenced with no NPI. Classic lagged dependency spatio-temporal IF models will be discussed and the importance of the ST component in nowcasting will be assessed. The real example of lockdowns for Covid-19 in two US states during 2020 and 2021 is provided. The degeneracy in prediction in longer time periods is highlighted and the wide confidence intervals characterize the forecasts.
Is apparent digestibility associated with residual feed intake and enteric methane emission in Nellore cattle?
Authors: Gianvecchio Sarah Bernardes , Sakamoto Leandro Sannomiya , Souza Luana Lelis , Benfica Lorena Ferreira , de Oliveira Santos Marcatto Juliana , de Paula Eduardo Marostegan , Canesin Roberta Carilho , dos Santos Gonçalves Cyrillo Joslaine , Albuquerque Lucia Galvão , Mercadante Maria Eugênia Zerlotti
Published: December 2022

Residual feed intake (RFI) detects animals that consume less dry matter (DM) adjusted for production and maintenance, and differences in the digestibility may explain differences in RFI among contemporaneous cattle. The aim of the study was to evaluate the relationship between digestibility, RFI, and enteric methane emission in growing Nellore cattle (Bos indicus) divergently classified based on RFI phenotypes and also on RFI breeding value. One hundred twenty-two Nellore cattle submitted to performance testing in two test groups (249±4.33 days of age, and 332±4.22 days of age at the beginning of the test) were classified based on residual feed intake (RFI). A sample of 80 animals classified as low RFI (−0.748±0.076 kg DM/day) or high RFI (0.775±0.075 kg DM/day) was evaluated regarding feed compounds digestibility, fecal excretion, and enteric methane (CH4, g/day) emission. There was no significant difference in feed compounds digestibility between the most and least efficient animals. However, DM intake (6.92 vs. 8.66 kg DM/day) and feed conversion (7.93 vs. 9.42 kg/kg) were lower in low RFI animals. On average, low RFI animals emitted 14.3 g less CH4per day (174 vs. 188 g CH4/day; P=0.02); however, CH4emission expressed as g/kg DM intake (23.1 vs. 20.1; P<0.01) and the percentage of gross energy intake lost as CH4(8.13 vs. 7.08%; P<0.01) were higher in these animals. There are clear benefits (economic and environmental) of using more feed efficient animals in the beef production chain, i.e., animals that exhibit lower feed intake, lower fecal excretion and lower enteric methane emission without differences in weight gain or body weight. Variations in feed efficiency among them cannot be explained by differences in DM or feed compounds digestibility. More efficient animals emit less enteric methane (CH4, g/day) than less efficient animals, probably as a result of lower DMI.
Cell-surface targeting of fluorophores inDrosophilafor rapid neuroanatomy visualization
Authors: Kirk Molly J. , Gold Arya , Ravi Ashvin , Sterne Gabriella R. , Scott Kristin , Miller Evan W.
Published: December 2022

Visualizing neuronal anatomy often requires labor-intensive immunohistochemistry on fixed and dissected brains. To facilitate rapid anatomical staining in live brains, we used genetically targeted membrane tethers that covalently link fluorescent dyes forin vivoneuronal labeling. We generated a series of extracellularly trafficked small molecule tethering proteins, HaloTag-CD41and SNAPf-CD4, which directly label transgene expressing cells with commercially available ligand substituted fluorescent dyes. We created stable transgenicDrosophilareporter lines which express extracellular HaloTag-CD4 and SNAPf-CD4 with LexA and Gal4 drivers. Expressing these enzymes in liveDrosophilabrains, we labeled the expression patterns of various Gal4 driver lines recapitulating histological staining in live brain tissue. Pan-neural expression of SNAPf-CD4 enabled registration of live brains to an existing template for anatomical comparisons. We predict that these extracellular platforms will not only become a valuable complement to existing anatomical methods but will also prove useful for future genetic targeting of other small molecule probes, drugs, and actuators.
A Generalized Multinomial Probabilistic Model for SARS-CoV-2 Infection Prediction and Public Health Intervention Assessment in an Indoor Environment
Authors: Li Victor OK , Lam Jacqueline CK , Sun Yuxuan , Han Yang , Chan Kelvin , Wang Shan-shan , Crowcroft Jon , Downey Jocelyn , Zhang Qi
Published: December 2022

SARS-CoV-2 Omicron has become the predominant variant globally. Current infection models are limited by the need for large datasets or calibration to specific contexts, making them difficult to cater for different settings. To ensure public health decision-makers can easily consider different public health interventions (PHIs) over a wide range of scenarios, we propose a generalized multinomial probabilistic model of airborne infection to systematically capture group characteristics, epidemiology, viral loads, social activities, environmental conditions, and PHIs, with assumptions made on social distancing and contact duration, and estimate infectivity over short time-span group gatherings. This study is related to our 2021 work published in Nature Scientific Reports that modelled airborne SARS-CoV-2 infection (Han, Lam, Li, et al., 2021).1It is differentiated from former works on probabilistic infection modelling in terms of the following: (1) predicting new cases arising from more than one infectious in a gathering, (2) incorporating additional key infection factors, and (3) evaluating the effectiveness of multiple PHIs on SARS-CoV-2 infection simultaneously. Although our results reveal that limiting group size has an impact on infection, improving ventilation has a much greater positive health impact. Our model is versatile and can flexibly accommodate other scenarios by allowing new factors to be added, to support public health decision-making.
Rare variants in SLC34A3 explain missing heritability of urinary stone disease
Authors: Sadeghi-Alavijeh Omid , Chan Melanie MY , Moochhala Shabbir ,   Genomics England Research Consortium, Howles Sarah , Gale Daniel P. , Böckenhauer Detlef
Published: December 2022

Urinary stone disease (USD) is a major health burden affecting >10% of the UK population at some time. While stone disease is strongly associated with lifestyle, genetic factors also predispose to USD: common genetic variants at multiple loci from genome-wide association studies account for 5% of the estimated 45% heritability of the disorder. We investigated the extent to which rare genetic variation contributes to the unexplained heritability of USD.

Among participants of the UK 100,000 genome project, we identified 374 unrelated individuals assigned diagnostic codes indicative of USD. We performed whole genome gene-based variant burden testing and polygenic risk scoring against a control population of 24,930 genetic ancestry matched controls.

We observed (and replicated in an independent dataset) exome-wide significant enrichment (P=2.61×10-07) of monoallelic rare, predicted damaging variants in SLC34A3 (previously associated with autosomal recessive hereditary hypophosphataemic rickets with hypercalciuria) present in 19 (5%) cases compared with 1.6% of controls. The risk of USD with a monoallelic SLC34A3 variant (OR=3.75, 95% CI 2.27-5.91) was greater than the top decile of polygenic risk (OR=2.31, 95% CI 1.12-3.51). Addition of the SLC34A3 variant binary to a linear model including polygenic score increased the estimated variance explained, increasing the liability adjusted pseudo-R2 from 5.1% to 14.2%. We also observed significant association at OR9K2, an olfactory receptor, but this signal was not replicated.

In this cohort rare variants in SLC34A3 were the most important genetic risk factor for USD, with levels of pathogenicity intermediate between the fully penetrant rare variants linked with Mendelian disorders and the weaker effects of common variants associated with USD. These findings explain some of the heritability unexplained by prior common variant GWAS.
High proportions of single-nucleotide variations associated with multidrug resistance in swine gut microbial populations
Authors: Feehan Brandi , Ran Qinghong , Monk Kourtney , Nagaraja T. G. , Tokach M. D. , Amachawadi Raghavendra G. , Lee Sonny T M
Published: December 2022

Background

Antimicrobial resistance (AMR) is a significant global public health concern associated with millions of deaths annually. Agriculture has been attributed as a leading factor in AMR and multidrug resistance (MDR) associated with swine production estimated as one of the largest agricultural consumers of antibiotics. Therefore, studying and understanding AMR in swine has global relevance. AMR research has received increased attention in recent years. However, we are still building our understanding of genetic variation within a complex gut microbiome system that impacts AMR and MDR. In order to evaluate the gut resistome, we evaluated genetic variation before, during, and after antibiotic treatments. We studied three treatment groups: non-antibiotic controls (C), chlortetracycline (CTC) treated, and tiamulin (TMU) treated. We collected fecal samples from each group and performed metagenomic sequencing for a longitudinal analysis of genetic variation and functions.

Results

We generated 772,688,506 reads and 81 metagenome assembled genomes (MAGs). Interestingly, we identified a subset of 11 MAGs with sustained detection and high sustained entropy (SDHSE). Entropy described genetic variation throughout the MAG. Our SDHSE MAGs were considered MDR as they were identified prior to, throughout, and after CTC and TMU treatments as well as in the C piglets. SDHSE MAGs were especially concerning as they harbored relatively high variation. Consistently high variation indicated that these microbial populations may contain hypermutable elements which has been associated with increased chance of AMR and MDR acquisition. Our SDHSE MAGs demonstrated that MDR organisms (MDRO) are present in swine, and likely additional hosts contributing to global AMR. Altogether, our study provides comprehensive genetic support of MDR populations within the gut microbiome of swine.
CLASPs stabilize the intermediate state between microtubule growth and catastrophe
Authors: Lawrence EJ , Chatterjee S , Zanic M
Published: December 2022

CLASPs regulate microtubules in many fundamental cellular processes. CLASPs stabilize dynamic microtubules by suppressing catastrophe and promoting rescue, the switch-like transitions between microtubule growth and shrinkage. However, the molecular mechanisms underlying CLASP’s activity are not understood. Here, we investigate the effects of CLASPs on distinct microtubule substrates in the absence of tubulin to gain insight into how CLASPs regulate microtubule dynamics. Surprisingly, we find that human CLASP1 depolymerizes stable microtubules in the presence of GTP, but not in the absence of nucleotide. Conversely, CLASP1 stabilizes dynamic microtubules upon tubulin dilution in the presence of GTP. Our results demonstrate that CLASP1 drives microtubule substrates with different inherent stabilities into the same slowly-depolymerizing state in the absence of tubulin in a nucleotide-dependent manner. We interpret this state as the pre-catastrophe intermediate state between microtubule growth and shrinkage. Thus, we conclude that CLASPs stabilize the intermediate state between microtubule growth and shrinkage to suppress microtubule catastrophe and promote rescue.
Cooperativity between Cas9 and hyperactive AID establishes broad and diversifying mutational footprints in base editors
Authors: Berríos Kiara N. , Barka Aleksia , Gill Jasleen , Serrano Juan C. , Bailer Peter F. , Parker Jared B. , Evitt Niklaus H. , Gajula Kiran S. , Shi Junwei , Kohli Rahul M.
Published: December 2022

The partnership of DNA deaminase enzymes with CRISPR-Cas nucleases is now a well-established method to enable targeted genomic base editing. However, an understanding of how Cas9 and DNA deaminases collaborate to shape base editor (BE) outcomes has been lacking. Here, we support a novel mechanistic model of base editing by deriving a range of hyperactive activation-induced deaminase (AID) base editors (hBEs) and exploiting their characteristic diversifying activity. Our model involves multiple layers of previously underappreciated cooperativity in BE steps including: (1) Cas9 binding can potentially exposebothDNA strands for ‘capture’ by the deaminase, a feature that is enhanced by guide RNA mismatches; (2) after strand capture, the intrinsic activity of the DNA deaminase can tune window size and base editing efficiency; (3) Cas9 defines the boundaries of editing on each strand, with deamination blocked by Cas9 binding to either the PAM or the protospacer; and (4) non-canonical edits on the guide RNA bound strand can be further elicited by changing which strand is nicked by Cas9. Leveraging insights from our mechanistic model, we create novel hBEs that can remarkably generate simultaneous C>T and G>A transitions over >65 bp with significant potential for targeted gene diversification.
A hostile context, very limited intervention theory and almost no change in outcomes: findings from a systematic realist review of health passports for Autistic adults
Authors: Ellis Rebecca , Williams Kathryn , Brown Amy , Healer Eleanor , Grant Aimee
Published: December 2022

Background

Autism is a normal part of cognitive diversity, resulting in communication and sensory processing differences, which can become disabling in a neurotypical world. Autistic people have an increased likelihood of physical and mental co-occurring conditions and die earlier than neurotypical peers. Inaccessible healthcare may contribute to this. Autism Health Passports (AHPs) are paper-based or digital tools which can be used to describe healthcare accessibility needs; they are recommended in UK clinical guidance. However, questions remained as to the theoretical underpinnings and effectiveness of AHPs.

Methods

We undertook a systematic literature search identifying studies focused on AHPs for adults (aged over 16 years) from five databases. Included literature was subjected to realist evaluation. Data were extracted using a standardised form, developed by the research team, which considered research design, study quality for realist review and theContext,Mechanisms andOutcomes (CMOs) associated with each AHP tool.

Findings

162 unique records were identified, and 13 items were included in the review. Only one item was considered high quality. Contextual factors focused on the inaccessibility of healthcare to Autistic patients and staff lack of confidence and training in supporting Autistic needs.Interventions were heterogeneous, with most sources reporting few details as to how they had been developed. The most frequently included contents were communication preferences.Mechanisms were often not stated or were inferred by the reviewers and lacked specificity.Outcomes were included in four studies and were primarily focused on AHP uptake, rather thanOutcomes which measured impact.

Conclusion

There is insufficient evidence to conclude that AHPs reduce the health inequalities experienced by Autistic people. Using an AHP tool alone, without the inclusion of the local Autistic community developing the tool, and a wider intervention, such as training for staff or the use of local champions, may mean that AHPs do not trigger anyMechanisms, and thus cannot affectOutcomes.
Near-critical tuning of cooperativity revealed by spontaneous switching in a protein signalling array
Authors: Keegstra Johannes M , Avgidis Fotios , Mulla Yuval , Parkinson John S , Shimizu Thomas S
Published: December 2022

Dynamic properties of allosteric complexes are crucial for cellular information processing. However, direct observations of allosteric switches have been limited to compact molecular assemblies. Here, we reportin vivoFRET measurements of spontaneous discrete-level fluctuations in the activity of theEscherichia colichemosensory array — an extensive membrane-associated assembly comprising thousands of molecules. Finite-size scaling analysis of the temporal statistics by a two-dimensional conformational spread model revealed nearest-neighbor coupling strengths within 3% of the Ising second-order phase transition, indicating that chemosensory arrays are poised at criticality. Our analysis yields estimates for the intrinsic timescale of conformational changes (~ 10 ms) of allosteric units, and identifies near-critical tuning as a design principle for balancing the inherent tradeoff between response amplitude and response speed in higher-order signaling assemblies.

One-setence summary

In vivomeasurements of protein signaling array fluctuations reveal an allosteric system poised at criticality.
Transcriptome and biochemical analysis pinpoint multi-layered molecular processes associated with iron deficiency tolerance in hexaploid wheat
Authors: Meena Varsha , Kaur Gazaldeep , Joon Riya , Shukla Anuj , Choudhary Promila , Singh Palvinder , Roy Joy K , Singh Bhupinder , Pandey Ajay K
Published: December 2022

Iron (Fe) is an essential nutrient for plants that is indispensable for many physiological activities. Although few genotypes were identified with contrasting tolerance to Fe deficiency, the molecular insight into the distinct biochemical and transcriptional responses determining the trait is poorly known. This study aimed to identify the molecular and biochemical basis for the contrasting Fe deficiency tolerance in wheat genotype showing tolerance to Fe deficiency (cv. Kanchan-KAN) compared to susceptible (cv. PBW343-PBW) cultivar. Under Fe deficiency, the KAN show delayed chlorosis, high SPAD values and low malondialdehyde activity compared to PBW. The shoot transcriptomics studies show that a large set of genes for photosynthetic pathways were highly induced in PBW, suggesting its sensitivity to Fe deficiency. Although, under Fe deficiency, both the cultivars show distinct molecular re-arrangements, including high expression of genes involved in Fe uptake (including membrane transporters) and mobilization, the gene expression level was higher in KAN. Furthermore, the KAN cultivar also shows high ubiquitination activity in the shoot tissue suggesting a high turnover of proteins in the tolerant cultivar. These observations were also co-related with the high root phytosiderophores biosynthesis and its release that contributes to the enhanced Fe translocation index in KAN. Overall, our work provides the key link to understanding the mechanistic insight for the Fe deficiency tolerance in hexaploid wheat. This will enable wheat breeders to select genotypes for better Fe use efficiency for agriculture.
Single-molecule visualization of stalled replication-fork rescue by theEscherichia coliRep helicase
Authors: Whinn Kelsey S. , Xu Zhi-Qiang , Jergic Slobodan , Sharma Nischal , Spenkelink Lisanne M. , Dixon Nicholas E. , van Oijen Antoine M. , Ghodke Harshad
Published: December 2022

Genome duplication occurs while the template DNA is bound by numerous DNA-binding proteins. Each of these proteins act as potential roadblocks to the replication fork and can have deleterious effects on cells. InEscherichia coli, these roadblocks are displaced by the accessory helicase Rep, a DNA translocase and helicase that interacts with the replisome. The mechanistic details underlying the coordination with replication and roadblock removal by Rep remain poorly understood. Through real-time fluorescence imaging of the DNA produced by individualE. colireplisomes and the simultaneous visualization of fluorescently-labeled Rep, we show that Rep continually surveils elongating replisomes. We found that this association of Rep with the replisome is stochastic and occurs independently of whether the fork is stalled or not. Further, we visualize the efficient rescue of stalled replication forks by directly imaging individual Rep molecules as they remove a model protein roadblock, dCas9, from the template DNA. Using roadblocks of varying DNA-binding stabilities, we conclude that replication restart is the rate-limiting step of stalled replication rescue.
Biased activation of the receptor tyrosine kinase HER2
Authors: Catapano Claudia , Rahm Johanna V , Omer Marjan , Teodori Laura , Kjems Jørgen , Dietz Marina S , Heilemann Mike
Published: December 2022

HER2 belongs to the ErbB sub-family of receptor tyrosine kinases and regulates cellular proliferation and growth. Different from other ErbB receptors, HER2 has no known ligand. Activation occurs through heterodimerization with other ErbB receptors and their cognate ligands. This suggests several possible activation paths of HER2 with ligand-specific, differential response, which so far remained unexplored. Using single-molecule tracking and the diffusion profile of HER2 as a proxy for activity, we measured the activation strength and temporal profile in live cells. We found that HER2 is strongly activated by EGFR-targeting ligands EGF and TGFα, yet with a distinguishable temporal fingerprint. The HER4-targeting ligands EREG and NRGβ1 showed weaker activation of HER2, a preference for EREG, and a delayed response to NRGβ1. Our results indicate a selective ligand response of HER2 that may serve as a regulatory element. Our experimental approach is easily transferable to other membrane receptors targeted by multiple ligands.

Highlights

HER2 exhibits heterogeneous motion in the plasma membrane

The fraction of immobile HER2 correlates with phosphorylation levels

Diffusion properties serve as proxies for HER2 activation

HER2 exhibits ligand-specific activation strength and temporal profiles

Graphical Abstract
Trust and performance: a contextual study of management change in private and public organisation
Authors: Karhapää Sari-Johanna , Savolainen Taina , Malkamäki Kirsti
Published: December 2022

Purpose

Although previous studies have addressed the positive relationship between trust and performance, existing research has paid limited attention to management that shapes valued organisation behaviours important for effectiveness and wellbeing. This paper examines how organisational trust and performance unfold in the context of one private and one public sector case organisation in management change.

Design/methodology/approach

A multiple case study design using qualitative methods is applied to analyse textual data gathered from management and employee perspectives, juxtaposing private and public organisations.

Findings

Management change renewed decision-making in both organisations through role clarification. Through clearer roles, expectations were better managed in the collaborating units of a private organisation case and of the employees in a public organisation case impacting on organisational ability and predictability. Along with organisational communication, these develop trust which seems to be reflected in employee job performance at the organisational level.

Originality/value

This paper contributes to the gap in qualitative, empirical and contextual research by providing understanding about how intra-organisational trust is related to performance. Further, this paper sheds light on the vulnerability within an organisation during management change and adds to the somewhat scarce studies of relationships between trust and performance by juxtaposing the two contexts. Consequently, this enables one to reveal different approaches to trust and performance between the two sectors.
BIM guidance to optimise the operational phase: defining information requirements based on ISO 19650
Authors: Ashworth Simon , Dillinger Michelle , Körkemeyer Karsten
Published: December 2022

Purpose

This paper aims to describe the development of guidance to help clients and operational teams to clearly define information requirements for projects using building information modelling (BIM). ISO 19650 standards highlight this as a critical first step to ensure adequate information is available to optimise built assets over their whole life cycle.

Design/methodology/approach

A document analysis of existing BIM guidance supported by literature was undertaken to answer the research questions: “What guidance already exists specific to clients? and Would additional guidance help clients to better fulfil their role as the ‘appointing party’ in line with ISO 19650?”

Findings

A research gap was established highlighting a lack of guidance specifically aimed to help clients formulate information requirements as the appointing party. This research makes recommendations for an approach to define the requirements and support successful outcomes for BIM projects.

Practical implications

This paper provides a standardised approach and a starting point for an appointing party to gather and structure information requirements in line with ISO 19650.

Originality/value

This paper considers BIM information requirements specifically from an operations perspective with a focus on the client and facility management team.
Achieving agreement on service needs in child protection. Comparing children’s, mothers’ and practitioners’ views over time and between approaches
Authors: Aaltio Elina , Kannasoja Sirpa
Published: December 2022

Purpose

While studies on service users’ participation and their perceptions on the quality of services exist, agreement between family members’ and practitioners’ assessments of the family’s situation has received less interest. The purpose of this paper is to investigate agreement and its effect on outcomes by comparing the viewpoints of three groups of informants (children, mothers and practitioners) in the context of statutory child protection in two study groups – one applying a systemic approach (SPM) and a service-as-usual control group (SAU).

Design/methodology/approach

A quasi-experimental repeated-measures study design was applied. Outcome data comprised 112 cases (SPM cases n = 56 and SAU cases n = 56) at three sites. Data was collected from all participants at baseline and six months later.

Findings

First, practitioners’ analyses of a child’s need for protection did not meet family members’ expressed need for help. Second, child–mother agreement on the need for service intervention at T1 predicted a decrease in practitioner-assessed abuse or neglect from T1 to T2. In this sample, no differences were found between the two groups.

Originality/value

This study highlights the importance of making explicit the viewpoints of children, parents and practitioners in casework and research to improve understanding of how their perspectives differ over the course of the process and how possible initial disagreements affect outcomes.
Identity work in the backstage: exploring the role of expatriate bubbles in identity work of self-initiated expatriate engineers through a Goffmanian lens
Authors: Papafilippou Vanda , Efthymiadou Christina
Published: December 2022

Purpose

While there is vast research on expatriate adjustment, it is still known very little on how self-initiated expatriates (SIEs) in particular might cope with identity conflicts and how they engage with identity work. What is more, although there is some literature on the existence of expatriate bubbles, this does not cover how these bubbles might impact identity work. The purpose of this paper is to explore identity work that is taking place within expatriate bubbles and thus advance our knowledge on both expatriate bubbles and expatriate adjustment.

Design/methodology/approach

The study reports on the analysis of in-depth, semi-structured interview data collected from 37 self-initiated expatriate engineers from Greece, Spain and Italy, currently residing in Bristol, UK.

Findings

Previous studies have argued that expatriate bubbles impede adjustment. The study analysis, however, shows that expatriate bubbles can be not only a powerful mechanism for coping with foreignness and strengthening their sense of belonging but also act as identity workspaces where SIEs engaged with identity work and navigated identity conflicts.

Originality/value

The present study addresses two empirical gaps: the paucity of literature on the identity work that self-initiated expatriates engage with and the paucity studies on self-initiated expatriate engineers. The study also has a theoretical contribution as, drawing upon a Goffmanian dramaturgical framework sheds light on the back regions of performance taking place within expatriate bubbles. Thus, showing how SIEs relax but also rehearse their performances in order to reduce any identity gaps triggered by the new organisational and national context.
The dark side of leave: how voluntary leave shapes preferences for male and female supervisors
Authors: Motro Daphna , Pittarello Andrea , Nolan Kevin P. , Shahani-Denning Comila , Lenaghan Janet A.
Published: December 2022

Purpose

To determine how different voluntary leaves of absence (parental vs. community service) affect individuals’ preferences for working with either male or female supervisors. Drawing on role congruity theory, the authors examined whether individuals would least prefer supervisors who took voluntary leave that violated role expectations.

Design/methodology/approach

In Study 1, participants (n = 372) evaluated supervisors who took different forms of leave (none vs. parental vs. community service). In Study 2 (n = 202), the authors tested an intervention to reduce negative bias toward males taking community service leave. In both studies the authors examined the sex of the supervisor (male vs. female) on perceptions of typicality and supervisor preference.

Findings

Males who took community service leave were perceived as most atypical and were least preferred as supervisors. However, providing relevant research-based information about typicality reduced this bias.

Practical implications

The results show that people respond negatively toward males who take community service leave. Managers can help reduce this bias by providing relevant research-based information regarding community service leave.

Originality/value

This work is among the first to explore the consequences of community service leave and how it interacts with supervisor sex. The authors also identify a simple way to reduce bias against males who take community service leave.