bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Future Water Allocation under Climate Variability and Land Management Change in an Agricultural Watershed
Authors: Phung Quang A. , Thompson Allen L. , Baffaut Claire , Costello Christine , John Sadler E.
Published: September 2022

Climate change and population growth are increasing demand for water, causing water shortages across the United States. Decision makers need to understand the impact of climate on water allocation, particularly for watersheds with agricultural activity. The Missouri Salt River Basin (SRB) was selected for this study due to its soil characteristics, agriculturally dominated land use, and because it contains a major reservoir, Mark Twain Lake (MTL), which is the regional source of drinking water. The goal was to evaluate future water allocation in the SRB given projections of future climate and changing land management practices. Future climate data were input to the Soil and Water Assessment Tool, from which discharge outputs to MTL were entered in the Water Evaluation and Planning model to evaluate 2020–2059 crop and drinking water shortages. Water allocation strategies identified potential conflicts among users through scenario‐based approaches. The difference between water demand and supply was projected to increase by 100% because of climate change, from 3 to 6 million m3. Under a dramatic scenario, where irrigated land quadrupled, water shortage could be up to 38.5 million m3 (1,200% increase). Water withdrawals from the MTL may help alleviate part of the projected shortage; however, on‐farm pond storage would likely be more practical and cost‐effective. Overall, the paper provides a methodology for water allocation strategy.
Delirium‐associated medication in people at risk: A systematic update review, meta‐analyses, and GRADE‐profiles
Authors: Reisinger Michael , Reininghaus Eva Z. , Biasi Johanna De , Fellendorf Frederike T. , Schoberer Daniela
Published: September 2022

Background

Drug‐associated delirium is a common but potentially preventable neuropsychiatric syndrome associated with detrimental outcomes. Empirical evidence for delirium‐associated medication is uncertain due to a lack of high‐quality studies. We aimed to further investigate the body of evidence for drugs suspected to trigger delirium.

Methods

A systematic update review and meta‐analyses of prospective studies presenting drug associations with incident delirium in adult study populations was conducted. Two authors independently searched MEDLINE, PsycINFO, Embase, and Google Scholar dated from October 1, 2009 to June 23, 2020, after screening a previous review published in 2011. The most reliable results on drug‐delirium associations were pooled in meta‐analyses using the random‐effects model. Quality of evidence was assessed using the GRADE‐approach. This study is preregistered with OSF (DOI https://doi.org.10.17605/OSF.IO/4PUHY).

Results

The 31 eligible studies, presenting results for 24 medication classes were identified. Meta‐analyses and GRADE level of evidence ratings show no increased delirium risk for Haloperidol (OR: 0.96, 95% CI 0.72–1.28; high‐quality evidence), Olanzapine (OR: 0.25, 95% CI 0.15–0.40), Ketamine (OR: 0.72, 95% CI 0.35–1.46) or corticosteroids (OR: 0.69, 95% CI 0.32–1.50; moderate quality evidence, respectively). Low‐level evidence suggests a three‐fold increased risk for anticholinergics (OR: 3.11, 95% CI 1.04–9.26). Opioids, benzodiazepines, H1‐antihistamines, and antidepressants did not reach reliable evidence levels in our analyses.

Conclusion

We investigated the retrievable body of evidence for delirium‐associated medication. The results of this systematic review were then interpreted in conjunction with other evidence‐based works and guidelines providing conclusions for clinical decision‐making.
PC‐DOT: Improving genomic prediction ability of principal component regression by DOT product
Authors: Sun Hao , Wei Meng , Xu Zhong , Bai Chunyan , Sun Boxing
Published: September 2022

Principal component regression (PC regression) is a useful method developed for prediction based on a dimension‐reducing strategy. Generally, the principal components (PCs) are added to the regression model one by one based on the eigenvalue (PC‐Eigen). Considering that some PCs with large eigenvalues may be poorly associated with the response variable, the PC‐Eigen may not be the best framework. Researchers previously tried to add PCs to the model based on their contribution to the sum of squares of the regression (PC‐SS) and they found that the performance of PC‐SS is generally lower than that of the PC‐Eigen. A standard approach for selecting the optimal set of PCs remains a challenge. Here, from the cosine similarity theory, we postulated that we could rank the PCs by dot product, and this framework (we called PC‐DOT) could help to preferentially extract PCs that are highly correlated with the response variable and meanwhile have a large eigenvalue. Based on one simulated and three real genomic datasets (a total of 15 traits), we tested the prediction ability of different frameworks. In general, the PC‐DOT method showed a better performance than both PC‐Eigen and PC‐SS. To facilitate the application of PC, we attached a series of R codes for different frameworks (https://github.com/SUNHAO‐JLU/Genome_Prediction‐PC_DOT). In addition, the HAT matrix was used to reduce the compute complex in reference data during the cross‐validation process. Our work may help researchers to better understand and carry out the PC regression model.
Ustekinumab during pregnancy in patients with inflammatory bowel disease: a prospective multicentre cohort study
Authors: Avni‐Biron Irit , Mishael Tali , Zittan Eran , Livne‐Margolin Moran , Zinger Adar , Tzadok Roie , Goldenberg Rosie , Kopylov Uri , Ron Yulia , Hadar Eran , Helman Sarit , Granovsky Sorina Grisaru , Ollech Jacob E. , Arazi Ayelet , Farkash Rivka , Pauker Maor H. , Yanai Henit , Dotan Iris , Shitrit Ariella Bar‐Gil
Published: September 2022

Background

Women with inflammatory bowel diseases (IBD) often receive biologics to maintain remission during pregnancy.

Aims

To assess maternal and neonatal outcomes in patients with IBD treated with ustekinumab (UST) during pregnancy

Methods

In a multicentre, prospective cohort study, we recruited women with IBD treated with UST during pregnancy between 2019 and 2021. Outcomes were compared among patients treated with UST, anti‐tumour necrosis factor α, (anti‐TNF) and non‐UST, non‐anti‐TNF therapies. UST‐treated patients were matched 1:2 to controls according to age, body mass index and parity. Newborns were followed up to 12 months.

Results

We recruited 129 pregnant patients: UST 27; anti‐TNF 52; non‐UST, non‐anti‐TNF 50 (thiopurine or mesalazine 30, no therapy 20); Crohn's disease 25 (96.9%). Overall, pregnancy, neonatal and newborn outcomes were satisfactory, with no significant differences among patients treated with UST, anti‐TNF and non‐UST non‐anti‐TNF agents for obstetrical maternal complications [UST 3 (11.5%), anti TNF 12 (23.1%), non UST, non‐anti‐TNF 4 (8.2%), p = 0.095], pre‐term delivery [1 (4.3%), 9 (18.4%), 4 (5.7%), p = 0.133], low birth weight [1 (4.2%), 5 (10.2%), 4 (8.3%), p = 0.679], or first year newborn hospitalisation [2 (9.1%), 4 (8.2%), 3 (6.1%), p = 0.885].

Conclusion

Pregnant patients with IBD treated with UST demonstrated favourable pregnancy and neonatal outcomes that were comparable with those in patients treated with anti‐TNF or other therapy. Data are reassuring for patients with IBD and their physicians when considering UST during pregnancy.
Fostering knowledge sharing: Design principles for persuasive digital technologies in open innovation projects
Authors: Jalowski Max , Oks Sascha Julian , Möslein Kathrin M.
Published: September 2022

Integrating knowledge is crucial for open innovation, and digital technologies can play a central role because they support knowledge sharing. In open innovation projects, in particular, little is known about the role of technology. Here, the individual behaviour of users is taken into account concerning the extent to which knowledge is shared. Therefore, persuasive technologies offer the potential to foster sharing. In particular, to facilitate the construction of future digital technologies, this study applies a design science research approach to create and analyse artefacts as a research contribution and develop design principles as a step towards a nascent design theory. We present insights from the design and application of three artefacts in different stages of open innovation processes. Results show that digital technologies can be used for various purposes: to build a common understanding, support design phases, communicate ideas and simplify the application of the technology for the user. Our research provides insights into the role of digital technologies for knowledge sharing in open innovation projects, and four design principles are found to facilitate the construction of future persuasive digital technologies for open innovation projects.
Abemaciclib plus fulvestrant in East Asian women with HR+, HER2− advanced breast cancer: Overall survival from MONARCH 2
Authors: Toi Masakazu , Huang Chiun‐Sheng , Im Young‐Hyuck , Sohn Joohyuk , Zhang Wei , Sakaguchi Sachi , Haddad Nadine , van Hal Gertjan , Sledge George W.
Published: September 2022

MONARCH 2 is a global, randomized, double‐blind, phase 3 study of abemaciclib/placebo + fulvestrant in patients with hormone receptor positive, human epidermal growth factor receptor 2‐negative advanced breast cancer. The East Asian population comprised 212 (31.7%) of the 669 intent‐to‐treat population in the MONARCH 2 trial. Consistent with the primary analysis, this subpopulation analysis of East Asian patients indicated progression‐free survival benefit in the abemaciclib arm. The median overall survival was not reached in the abemaciclib arm and was 48.9 months in the placebo arm (hazard ratio 0.80; 95% confidence interval 0.52–1.24; p = 0.377). In addition, other efficacy endpoints, including time to chemotherapy, chemotherapy free survival, and time to second disease progression, indicated benefit in the abemaciclib arm. This analysis found no new safety concerns with longer follow‐up. These findings support the positive benefit–risk balance of the MONARCH 2 regimen in East Asian patients with hormone receptor positive, human epidermal growth factor receptor 2‐negative advanced breast cancer.
Evaluating near‐infrared photoimmunotherapy for targeting fibroblast activation protein‐α expressing cells in vitro and in vivo
Authors: Jin Jiefu , Barnett James D. , Krishnamachary Balaji , Mironchik Yelena , Luo Catherine K. , Kobayashi Hisataka , Bhujwalla Zaver M.
Published: September 2022

Photoimmunotherapy (PIT), carried out using an Ab conjugated to the near infrared dye IRDye700DX, is achieving significant success in target‐specific elimination of cells. Fibroblast activation protein alpha (FAP‐α) is an important target in cancer because of its expression by cancer‐associated fibroblasts (CAFs) as well as by some cancer cells. Cancer‐associated fibroblasts that express FAP‐α have protumorigenic and immune suppressive functions. Using immunohistochemistry of human breast cancer tissue microarrays, we identified an increase of FAP‐α+ CAFs in invasive breast cancer tissue compared to adjacent normal tissue. We found FAP‐α expression increased in fibroblasts cocultured with cancer cells. In proof‐of‐principle studies, we engineered human FAP‐α overexpressing MDA‐MB‐231 and HT‐1080 cancer cells and murine FAP‐α overexpressing NIH‐3T3 fibroblasts to evaluate several anti‐FAP‐α Abs and selected AF3715 based on its high binding affinity with both human and mouse FAP‐α. After conjugation of AF3715 with the phthalocyanine dye IR700, the resultant Ab conjugate, FAP‐α‐IR700, was evaluated in cells and tumors for its specificity and effectiveness in eliminating FAP‐α expressing cell populations with PIT. Fibroblast activation protein‐α‐IR700‐PIT resulted in effective FAP‐α‐specific cell killing in the engineered cancer cells and in two patient‐derived CAFs in a dose‐dependent manner. Following an intravenous injection, FAP‐α‐IR700 retention was three‐fold higher than IgG‐IR700 in FAP‐α overexpressing tumors, and two‐fold higher compared to WT tumors. Fibroblast activation protein‐α‐IR700‐PIT resulted in significant growth inhibition of tumors derived from FAP‐α overexpressing human cancer cells. A reduction of endogenous FAP‐α+ murine CAFs was identified at 7 days after FAP‐α‐IR700‐PIT. Fibroblast activation protein‐α‐targeted near infrared PIT presents a promising strategy to eliminate FAP‐α+ CAFs.
High levels of AXL expression in untreated EGFR‐mutated non‐small cell lung cancer negatively impacts the use of osimertinib
Authors: Yoshimura Akihiro , Yamada Tadaaki , Serizawa Masakuni , Uehara Hisanori , Tanimura Keiko , Okuma Yusuke , Fukuda Akito , Watanabe Satoshi , Nishioka Naoya , Takeda Takayuki , Chihara Yusuke , Takemoto Shinnosuke , Harada Taishi , Hiranuma Osamu , Shirai Yukina , Shukuya Takehito , Nishiyama Akihiro , Goto Yasuhiro , Shiotsu Shinsuke , Kunimasa Kei , Morimoto Kenji , Katayama Yuki , Suda Kenichi , Mitsudomi Tetsuya , Yano Seiji , Kenmotsu Hirotsugu , Takahashi Toshiaki , Takayama Koichi
Published: September 2022

For non‐small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, the initial therapeutic interventions will have crucial impacts on their clinical outcomes. Drug tolerant factors reportedly have an impact on EGFR‐tyrosine kinase inhibitor sensitivity. This prospective study investigated the impacts of drug tolerant‐related protein expression in tumors based on the efficacy of osimertinib in the first‐setting of EGFR‐mutated advanced NSCLC patients. A total of 92 patients with EGFR‐mutated advanced or postoperative recurrent NSCLC were analyzed and treated with osimertinib at 14 institutions in Japan. AXL, p53, and programmed death‐ligand 1 (PD‐L1) expression in patient tumors was determined using immunohistochemistry. The AXL signaling pathway was investigated using a cell line‐based assay and AXL‐related gene expression in The Cancer Genome Atlas (TCGA) database. High levels of AXL and positive‐p53 expression were detected in 26.1% and 53.3% of the pretreatment EGFR‐mutated NSCLC tumors, respectively. High AXL expression levels were significantly associated with a shorter progression‐free survival compared with low AXL expression levels, irrespective of the EGFR activating mutation status (p = 0.026). Cell line‐based assays indicated that the overexpression of AXL protein accelerated PD‐L1 expression, which induced insensitivity to osimertinib. In the TCGA database, AXL RNA levels were positively correlated with PD‐L1 expression in the lung adenocarcinoma cohort. The results show that high AXL expression levels in tumors impact clinical predictions when using osimertinib to treat EGFR‐mutated NSCLC patients. Trial Registration: UMIN000043942.
GAN‐C: A generative adversarial network with a classifier for effective event prediction
Authors: Rajita B. S. A. S. , Halani Vrutik , Shah Dhruvil , Panda Subhrakanta
Published: September 2022

Event prediction is essential in social network (SN) analysis to study the SN's evolutionary patterns (communities). Machine learning (ML) models are often used to predict events in SN communities. The ML algorithms manifest the results with biasness for the same dataset. Hence, the performance of an ML model requires validation for the unseen data to avoid biasness in learning. Generally, researchers use the generative adversarial network (GAN) model for generating realistic sample data to enhance the prediction of events. It is challenging for the discriminator to learn features using a single layer with similar weights in a conventional GAN technique. Therefore, this article proposes an improved version of the GAN model named generative adversarial network classifier (GAN‐C). The proposed GAN‐C model contains an additional layer, called classifier, that generates different feature maps. Wherein weights are adjusted dynamically based on the conditions to predict the events. To be precise, conditioning the weights in a classifier layer using entropy values of the features is a simple and effective way to minimize the classifier loss function (categorical cross‐entropy). GAN‐C model results in 16% loss up to 10 batches, and after that, the loss becomes negligible and can generate non‐overlapping events. The gaps between such non‐overlapping events are analyzed using the Jensen–Shannon divergence technique. The experimental results show that the existing single‐GAN and multi‐GAN methods predict events with 79.34% and 82.17% accuracy, respectively. While the proposed GAN‐C comparatively predicts events with improved accuracy of 88.56% on the same dataset. The data generated by the GAN‐C model are also approximately 55.85% and 80.59% more realistic than multi‐GAN and single‐GAN, respectively, based on root mean square error and inception score comparisons. GAN‐C is also approximately 68.01% faster than other GAN models. Thus, this article's theoretical and experimental analysis justifies that GAN‐C works suitably for predicting events in a massive dataset.
Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalised adults with severe COVID‐19 pneumonia: An open‐label randomised trial
Authors: Corral‐Gudino Luis , Cusacovich Ivan , Martín‐González Jose Ignacio , Muela‐Molinero Alberto , Abadía‐Otero Jésica , González‐Fuentes Roberto , Ruíz‐de‐Temiño Ángela , Tapia‐Moral Elena , Cuadrado‐Medina Francisca , Martín‐Asenjo Miguel , Miramontes‐González Pablo , Delgado‐González Jose Luis , Ines Sandra , Abad‐Manteca Laura , Usategui‐Martín Iciar , Ruiz‐Albi Tomás , Miranda‐Riaño Sara , Rodríguez‐Fortúnez Patricia , Rodríguez‐Jiménez Consuelo , López‐Franco Esperanza , Marcos Miguel ,   MP3 pulses COVID‐19 collaborative group
Published: September 2022

Background

The efficacy and safety of high versus medium doses of glucocorticoids for the treatment of patients with COVID‐19 has shown mixed outcomes in controlled trials and observational studies. We aimed to evaluate the effectiveness of methylprednisolone 250 mg bolus versus dexamethasone 6 mg in patients with severe COVID‐19.

Methods

A randomised, open‐label, controlled trial was conducted between February and August 2021 at four hospitals in Spain. The trial was suspended after the first interim analysis since the investigators considered that continuing the trial would be futile. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 mg once daily for up to 10 days or methylprednisolone 250 mg once daily for 3 days.

Results

Of the 128 randomised patients, 125 were analysed (mean age 60 ± 17 years; 82 males [66%]). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group versus 4.8% in the 6 mg dexamethasone group (absolute risk difference, 0.1% [95% CI, −8.8 to 9.1%]; p = 0.98). None of the secondary outcomes (admission to the intensive care unit, non‐invasive respiratory or high‐flow oxygen support, additional immunosuppressive drugs, or length of stay), or prespecified sensitivity analyses were statistically significant. Hyperglycaemia was more frequent in the methylprednisolone group at 27.0 versus 8.1% (absolute risk difference, −18.9% [95% CI, −31.8 to ‐ 5.6%]; p = 0.007).

Conclusions

Among severe but not critical patients with COVID‐19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation.
Effect of the presence of predatory cues and hunger on cannibalistic behaviour of ladybird beetle,Menochilus sexmaculatusFabricius (Coleoptera: Coccinellidae)
Authors: Yadav Tripti , Omkar  , Mishra Geetanjali
Published: September 2022

Cannibalism and its role in population dynamics, along with various factors influencing the rate of cannibalism, have been widely studied across taxa.

The effects of predatory cue concentrations and starvation on cannibalistic tendencies and other life‐history traits in cannibalistic and non‐cannibalistic adults ofMenochilus sexmaculatuswere investigated.

Egg cannibalism increased with increasing predatory cue concentration and was maximum in high predatory cue treatment; increased with starvation irrespective of their diet history.

Latency to cannibalise eggs was shorter for cannibalistic adults as compared to non‐cannibalistic adults irrespective of their hunger status and concentration of conspecific cues.

Non‐cannibalistic females have higher fecundity than cannibalistic females.

In conclusion, both cannibalistic and non‐cannibalistic individuals respond differently to intrinsic (hunger) and extrinsic cues (predatory cue concentrations). Cannibalistic individuals cannibalise more than non‐cannibalistic ones at low levels of starvation and predatory cues.

Our finding suggests that cannibalistic individuals are better at assessing the risk and removing future competitors, which might favour these individuals over non‐cannibalistic ones in adverse conditions and increased competition.
Multiple sclerosis risk variants influence the peripheral B‐cell compartment early in life in the general population
Authors: de Mol Casper L. , van Luijn Marvin M. , Kreft Karim L. , Looman Kirsten I. M. , van Zelm Menno C. , White Tonya , Moll Henriette A. , Smolders Joost , Neuteboom Rinze F.
Published: September 2022

Background and purpose

Multiple sclerosis (MS) is associated with abnormal B‐cell function, and MS genetic risk alleles affect multiple genes that are expressed in B cells. However, how these genetic variants impact the B‐cell compartment in early childhood is unclear. In the current study, we aim to assess whether polygenic risk scores (PRSs) for MS are associated with changes in the blood B‐cell compartment in children from the general population.

Methods

Six‐year‐old children from the population‐based Generation R Study were included. Genotype data were used to calculate MS‐PRSs and B‐cell subset‐enriched MS‐PRSs, established by designating risk loci based on expression and function. Analyses of variance were performed to examine the effect of MS‐PRSs on total B‐cell numbers (n = 1261) as well as naive and memory subsets (n = 675).

Results

After correction for multiple testing, no significant associations were observed between MS‐PRSs and total B‐cell numbers and frequencies of subsets therein. A naive B‐cell‐MS‐PRS (n = 26 variants) was significantly associated with lower relative, but not absolute, naive B‐cell numbers (p = 1.03 × 10−4 and p = 0.82, respectively), and higher frequencies and absolute numbers of CD27+ memory B cells (p = 8.83 × 10−4 and p = 4.89 × 10−3, respectively). These associations remained significant after adjustment for Epstein–Barr virus seropositivity and the HLA‐DRB1*15:01 genotype.

Conclusions

The composition of the blood B‐cell compartment is associated with specific naive B‐cell‐associated MS risk variants during childhood, possibly contributing to MS pathophysiology later in life. Cell subset‐specific PRSs may offer a more sensitive tool to define the impact of genetic risk on the immune system in diseases such as MS.
Youth participation in environmental action in Vietnam: Learning citizenship in liminal spaces
Authors: Beckwith Laura , Smith Matt Baillie , Hensengerth Oliver , Nguyen Hue , Greru Chamithri , Warrington Siobhan , Nguyen Tanh , Smith Graham , Minh Thuy Mai Thi , Nguyen Lan , Woolner Pamela
Published: September 2022

Youth participation has become an important element of environmental governance and is also a way that young people learn about the expectations of citizenship. In the global South, young people are confronted with multiple understandings of citizenship as international development organisations may introduce citizenship in a liberal, democratic framing which may differ from national citizenship norms. In Vietnam, state agencies have a history of supporting youth participation linked to nation building and community service. These activities create an imaginary which highlights citizenship as a status and the national scale as being central. More recently, liberalisation policies have opened the door for activities of international organisations which extend imaginaries of citizenship to the global scale and beyond status to a process centred on creating a sense of belonging. Other forms of participation are also flourishing, thanks to the increasing reach of social media. This paper explores how the diversity of this landscape creates liminal spaces of citizenship which young people navigate, working within and between different scales and imaginaries.
Incidence and predictors of sternal surgical wound infection in cardiac surgery: A prospective study
Authors: Arribas‐Leal José María , Rivera‐Caravaca José Miguel , Hernández‐Torres Alicia , Jiménez‐Aceituna Antonio , Moral‐Escudero Encarnación , Pérez‐Andreu Joaquín , García‐Vázquez Elisa , Gutiérrez‐García Francisco , García‐Puente Julio J. , Marín Francisco , Cánovas‐López Sergio J. , Herrero‐Martínez José Antonio
Published: September 2022

Sternal surgical wound infection (SSWI) in cardiac surgery is associated with increased morbidity. We investigated the incidence of SSWI, the main germs implicated and predictors of SSWI. Prospective study including patients undergoing full median sternotomy between January 2017 and December 2019. Patients were followed‐up for 3 months after hospital discharge. All sternal wound infections up to 90 days after discharge were considered SSWI. 1004 patients were included. During follow‐up, 68 (6.8%) patients presented SSWI. Patients with SSWI had a higher incidence of postoperative renal failure (29.4% vs 17.1%, P = .007), a higher incidence of early postoperative reoperation for non‐infectious causes (42.6% vs 9.1%, P < .001), longer ICU stay (3 [2–9] days vs 2 [2–4] days, P = .006), and longer hospital stay (24.5 [14.8–38.3] days vs 10 [7–18] days, P < .001). Gram‐positive germs were presented in 49% of the cultures, and gram‐negative bacteria in 35%. Early reoperation for non‐infectious causes (OR 4.90, 95% CI 1.03–23.7), and a longer ICU stay (OR 1.37 95% CI 1.10–1.72) were independent predictors of SSWI. SSWI is rare but leads to more postoperative complications. The need for early reoperation because of non‐infectious cause and a longer ICU stay were independently associated with SSWI.
Interrogation of TERT promoter hotspot mutations in ameloblastoma and ameloblastic carcinoma
Authors: Magalhães Maria Carolina Silva Versieux , Felix Fernanda Aragão , Guimarães Letícia Martins , dos Santos Jean Nunes , de Marco Luiz Armando , Gomez Ricardo Santiago , Gomes Carolina Cavaliéri , de Sousa Sílvia Ferreira
Published: September 2022

Background

TERT promoter mutations increase telomerase activity, conferring cell immortality. The coexistence of TERT promoter mutations with BRAFV600E is associated with aggressiveness. Ameloblastoma and ameloblastic carcinoma are infiltrative neoplasms that harbor BRAFV600E; however, it remains unknown if these odontogenic tumors also show TERT promoter mutations.

Methods

Genomic DNA of paraffin‐embedded ameloblastomas (n = 6) and ameloblastic carcinomas (n = 3) were Sanger‐sequenced to assess the hotspot TERT promoter mutations C228T and C250T. BRAFV600E status was screened by TaqMan allele‐specific quantitative polymerase chain reaction.

Results

None of the samples harbored TERT promoter mutations. The BRAFV600E mutation was positive in 3 of 6 of ameloblastomas and in 1 of 3 of ameloblastic carcinomas.

Conclusion

The absence of TERT promoter mutation in the samples indicates that this molecular event is not relevant to the tumors' pathogenesis. Further studies are necessary to explore undefined genetic or epigenetic mechanisms related to TERT‐upregulation in ameloblastoma, and the telomerase activity in ameloblastic carcinoma.
A complete digital approach for facially generated full arch diagnostic wax up, guided surgery, and implant‐supported interim prosthesis by integrating 3D facial scanning, intraoral scan and CBCT
Authors: Amin Sara A. , Hann Sean , Elsheikh Ahmad Khater , Boltchi Farhad , Zandinejad Amirali
Published: September 2022

Continuous innovation in digital dental technology offers new prospects for creating a complete virtual environment. The technique described adds a facial approach to the conventional digital workflow by incorporating 3D face scans to cone beam computed tomography and intraoral scans. Using this workflow, clinicians can obtain a complete virtual patient for facially generated diagnostic wax up and plan and implement a predictable implant placement and interim prosthesis. This technique provides a full digital workflow for restoratively‐driven computer‐aided implant planning, guided surgery, and 3D printing of an interim complete‐arch fixed implant‐supported prosthesis.
Expression of periodontitis susceptibility genes in human gingiva using single‐cell RNA sequencing
Authors: Caetano Ana J. , D'Agostino Eleanor M. , Sharpe Paul , Nibali Luigi
Published: September 2022

Objective

Single‐cell transcriptomics was used to determine the possible cell‐type specificity of periodontitis susceptibility genes.

Background

The last decade has witnessed remarkable advances in the field of human genomics. Despite many advances, the genetic factors associated with or contributing to the periodontitis pathogenesis have only been identified to a limited extent and are often poorly validated. Confirming whether a given single nucleotide polymorphism has an association with periodontitis requires a robust mechanistic explanation on the functional consequences of a given genetic variant.

Methods

We globally assessed the expression of 26 disease‐associated genes identified by GWAS within the gingival mucosa. A total of 12 411 cells from 4 different donors were analysed. Differentially expressed genes were analysed using Seurat, a non‐parametric Wilcoxon rank sum test. The minimum threshold for significance was defined as p < .05.

Results

This exploration at a cellular‐level suggests diverse populations contributing to disease pathogenesis, with macrophages expressing a higher number of the analysed disease‐associated genes. IL1B, PTGS2, FCGR2A, IL10 and IL1A specifically showed a more restricted expression in the myeloid lineages.

Conclusion

This short report combines human genetics and single‐cell genomics to better understand periodontitis by mapping variants to predict their cells of action and putative functions. These findings seem to suggest that innate cell dysfunction is linked to disease susceptibility.
A prospective examination of swallow and cough dysfunction after lung transplantation
Authors: Dallal‐York Justine , Croft Kayla , Anderson Amber , DiBiase Lauren , Donohue Cara , Vasilopoulos Terrie , Shahmohammadi Abbas , Pelaez Andres , Pipkin Mauricio , Hegland Karen W. , Machuca Tiago N. , Plowman Emily K.
Published: September 2022

Objectives

Swallow and cough dysfunction are possible surgical complications of lung transplantation (LT). We examined voluntary cough strength, sensorimotor reflexive cough integrity, and swallow‐related respiratory rate (RR) across swallowing safety and aspiration response groups in recovering LT recipients.

Methods

Forty‐five LT recipients underwent flexible endoscopic evaluation of swallowing indexed by the validated Penetration Aspiration Scale. RR before and after a 3‐ounce water drinking task was measured. Voluntary and reflexive cough screening were performed to index motor and sensory outcomes. T‐tests, one‐way ANOVAs, and chi‐square (odds ratios) were used.

Results

60% of patients exhibited laryngeal penetration (n = 27) and 40% demonstrated tracheal aspiration (n = 18); 72% (n = 13) demonstrated silent aspiration. Baseline RR was higher in aspirators versus non‐aspirators (26.5 vs. 22.6, p = 0.04) and in silent aspirators compared to non‐silent aspirators (27.9 vs. 20.7, p = 0.01). RR change post‐swallowing did not differ between aspiration response groups; however, it was significantly higher in aspirators compared to non‐aspirators (3 vs. −2, p = 0.02). Compared to non‐silent aspirators, silent aspirators demonstrated reduced voluntary cough peak expiratory flow (PEF; 166 vs. 324 L/min, p = 0.01). PEF, motor and urge to cough reflex cough ratings did not differ between aspirators and non‐aspirators. Silent aspirators demonstrated a 7.5 times higher odds of failing reflex cough screening compared to non‐silent aspirators (p = 0.07).

Conclusions

During the acute recovery period, all LT participants demonstrated some degree of unsafe swallowing and reduced voluntary cough strength. Silent aspirators exhibited elevated RR, reduced voluntary cough physiologic capacity to defend the airway, and a clinically distinguishable blunted motor response to reflex cough screening.
Differential sensitivity of metabolic pathways in sugar beet roots to combined salt, heat, and light stress
Authors: García‐Caparrós Pedro , Vogelsang Lara , Persicke Marcus , Wirtz Markus , Kumar Vijay , Dietz Karl‐Josef
Published: September 2022

Plants in nature commonly encounter combined stress scenarios. The response to combined stressors is often unpredictable from the response to single stresses. To address stress interference in roots, we applied salinity, heat, and high light to hydroponically grown sugar beet. Two main patterns of metabolomic acclimation were apparent. High salt of 300 mM NaCl considerably lowered metabolite amounts, for example, those of most amino acids, γ‐amino butyric acid (GABA), and glucose. Very few metabolites revealed the opposite trend with increased contents at high salts, mostly organic acids such as citric acid and isocitric acid, but also tryptophan, tyrosine, and the compatible solute proline. High temperature (31°C vs. 21°C) also frequently lowered root metabolite pools. The individual effects of salinity and heat were superimposed under combined stress. Under high light and high salt conditions, there was a significant decline in root chloride, mannitol, ribulose 5‐P, cysteine, and l‐aspartate contents. The results reveal the complex interaction pattern of environmental parameters and urge researchers to elaborate in much more detail and width on combinatorial stress effects to bridge work under controlled growth conditions to growth in nature, and also to better understand acclimation to the consequences of climate change.
Tweakments: Non‐surgical beauty technologies and future directions for the sociology of the body
Authors: Dowrick Anna , Holliday Ruth
Published: September 2022

Science, aesthetics, the body, and the concerns they attach to, such as gender, ‘race’, class, age and consumer culture, are key objects of sociological investigation. These discourses have been reignited in recent years by changes in the availability, accessibility and affordability of medicalised cosmetic procedures. The most popular of these procedures are non‐surgical ‘tweakments’ to the shape and/or appearance of the face, usually through use of ‘injectables’ such as Botox and dermal fillers. This shift in focus from surgical procedures to minimally invasive injections has led more practitioners to join the market of potential providers and a wider variety of consumers to seek them out. This has been accompanied by panic about the risks to bodies and aesthetic standards if stewardship of beauty should fall into the wrong hands. We trace the history of medicalised cosmetic practices and academic discourses on the body, particularly how cosmetic practices are understood to produce the body as gendered and racialised. We then suggest future approaches for exploring the sociological significance of new cosmetic practices. We encourage researchers to explore how imaginaries of (un)desirable bodies shape debates about appropriate use of non‐surgical cosmetic procedures, alongside investigation of the situated intersections of identity that are inscribed on bodies.
Zygomatic arch reconstruction with apatient‐specificpolycaprolactone/beta‐tricalciumphosphate scaffold after parosteal osteosarcoma resection in a dog
Authors: Kang Kyu‐Won , Shim Jin‐Hyung , Kim Hyun‐Jung , Kang Byung‐Jae
Published: September 2022

Objective

To describe the surgical application of a 3D–printing‐based, patient‐specific, biocompatible polycaprolactone/beta‐tricalcium phosphate (PCL/β‐TCP) scaffold to reconstruct the zygomatic arch after tumor resection in a dog.

Animal

A 13 year old female spayed Maltese.

Study design

Case report

Methods

The dog's presenting complaint was swelling ventral to her right eye. A round mass arising from the caudal aspect of the right zygomatic arch was identified by computed tomography (CT). The histopathologic diagnosis was a low‐grade spindle‐cell tumor. Surgical resection was planned to achieve 5 mm margins. A patient‐specific osteotomy guide and polycaprolactone/beta‐tricalcium phosphate (PCL/β‐TCP) scaffold were produced. Osteotomy, including 30% of total zygomatic arch length, was performed using an oscillating saw aligned with the guide. The scaffold was placed in the defect. Parosteal osteosarcoma was diagnosed based on histopathological examination. Excision was complete, with the closest margin measuring 0.3 mm.

Results

Mild epiphora, due to surgical site swelling, subsided after 20 days. Tissue formation within and around the porous scaffold was noted on CT 10 months postoperatively, with no evidence of metastasis or local recurrence. Facial conformation appeared symmetrical, and no complications were noted 16 months postoperatively.

Conclusion

The use of a 3D–printing‐based, patient‐specific, biocompatible PCL/β‐TCP scaffold successfully restored the structure and function of the zygomatic arch without complications, even following wide zygomectomy for complete tumor removal.
Indirect Tool Condition Monitoring Using Ensemble Machine Learning Techniques
Authors: Schueller Alexandra , Saldaña Christopher
Published: September 2022

Tool condition monitoring (TCM) has become a research area of interest due to its potential to significantly reduce manufacturing costs while increasing process visibility and efficiency. Machine learning (ML) is one analysis technique which has demonstrated advantages for TCM applications. However, the commonly studied individual ML models lack generalizability to new machining and environmental conditions, as well as robustness to the unbalanced datasets which are common in TCM. Ensemble ML models have demonstrated superior performance in other fields, but have only begun to be evaluated for TCM. As a result, it is not well understood how their TCM performance compares to that of individual models, or how homogeneous and heterogeneous ensemble models’ performances compare to one another. To fill in these research gaps, milling experiments were conducted using various cutting conditions, and the model groups were compared across several performance metrics. Statistical t-tests were also used to evaluate the significance of model performance differences. Through the analysis of four individual ML models and five ensemble models, all based on the processes’ sound, spindle power, and axial load signals, it was found that on average, the ensemble models performed better than the individual models, and that the homogeneous ensembles outperformed the heterogeneous ensembles.
Constructing Three-Dimensional Honeycomb Structures Based on Origami Geometry
Authors: Saito Kazuya , Fujimoto Akinobu , Okabe Yoji
Published: September 2022

Origami has shown the potential to design unique mechanical properties and complex three-dimensional shapes by folding through designed crease patterns on flat materials. The authors investigated a new honeycomb-based origami metamaterial called “kirigami honeycomb.” Resembling origami, kirigami honeycomb allows a single flat sheet of material with periodic slits to be folded into a honeycomb shape. Previous studies have reported successful use of this method to create various honeycomb shapes, changing only the folding line diagrams (FLDs). These previous studies have, however, considered only one-directional cross-sectional modifications; the core thickness and curvature changed only in the W-direction. This study proposes a new method that will support complex 3D honeycomb designs made from single flat sheets. A newly defined crease pattern conversion method provides arbitrary scaling of the honeycomb shape in the L-direction. The combined FLD and pattern conversion design methods encourage the cost-effective manufacture of 3D shaped honeycombs from single flat paper sheets. The proposed method is implemented to the design software, enabling to design arbitrary cross-sectional honeycomb cores with optional L-directional scaling.
Circadian disruption enhances HSF1 signaling and tumorigenesis in
Kras
-driven lung cancer
Authors: Pariollaud Marie , Ibrahim Lara H. , Irizarry Emanuel , Mello Rebecca M. , Chan Alanna B. , Altman Brian J. , Shaw Reuben J. , Bollong Michael J. , Wiseman R. Luke , Lamia Katja A.
Published: September 2022

Disrupted circadian rhythmicity is a prominent feature of modern society and has been designated as a probable carcinogen by the World Health Organization. However, the biological mechanisms that connect circadian disruption and cancer risk remain largely undefined. We demonstrate that exposure to chronic circadian disruption [chronic jetlag (CJL)] increases tumor burden in a mouse model of KRAS-driven lung cancer. Molecular characterization of tumors and tumor-bearing lung tissues revealed that CJL enhances the expression of heat shock factor 1 (HSF1) target genes. Consistently, exposure to CJL disrupted the highly rhythmic nuclear trafficking of HSF1 in the lung, resulting in an enhanced accumulation of HSF1 in the nucleus. HSF1 has been shown to promote tumorigenesis in other systems, and we find that pharmacological or genetic inhibition of HSF1 reduces the growth of KRAS-mutant human lung cancer cells. These findings implicate HSF1 as a molecular link between circadian disruption and enhanced tumorigenesis.
Constraining the formation and transport of lunar impact glasses using the ages and chemical compositions of Chang’e-5 glass beads
Authors: Long Tao , Qian Yuqi , Norman Marc D. , Miljkovic Katarina , Crow Carolyn , Head James W. , Che Xiaochao , Tartèse Romain , Zellner Nicolle , Yu Xuefeng , Xie Shiwen , Whitehouse Martin , Joy Katherine H. , Neal Clive R. , Snape Joshua F. , Zhou Guisheng , Liu Shoujie , Yang Chun , Yang Zhiqing , Wang Chen , Xiao Long , Liu Dunyi , Nemchin Alexander
Published: September 2022

Impact glasses found in lunar soils provide a possible window into the impact history of the inner solar system. However, their use for precise reconstruction of this history is limited by an incomplete understanding of the physical mechanisms responsible for their origin and distribution and possible relationships to local and regional geology. Here, we report U-Pb isotopic dates and chemical compositions of impact glasses from the Chang’e-5 soil and quantitative models of impact melt formation and ejection that account for the compositions of these glasses. The predominantly local provenance indicated by their compositions, which constrains transport distances to <~150 kilometers, and the age-frequency distribution are consistent with formation mainly in impact craters 1 to 5 kilometers in diameter. Based on geological mapping and impact cratering theory, we tentatively identify specific craters on the basaltic unit sampled by Chang’e-5 that may have produced these glasses and compare their ages with the impact record of the asteroid belt.
Improving breast cancer diagnostics with deep learning for MRI
Authors: Witowski Jan , Heacock Laura , Reig Beatriu , Kang Stella K. , Lewin Alana , Pysarenko Kristine , Patel Shalin , Samreen Naziya , Rudnicki Wojciech , Łuczyńska Elżbieta , Popiela Tadeusz , Moy Linda , Geras Krzysztof J.
Published: September 2022

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has a high sensitivity in detecting breast cancer but often leads to unnecessary biopsies and patient workup. We used a deep learning (DL) system to improve the overall accuracy of breast cancer diagnosis and personalize management of patients undergoing DCE-MRI. On the internal test set (
n
= 3936 exams), our system achieved an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% CI: 0.92 to 0.93). In a retrospective reader study, there was no statistically significant difference (
P
= 0.19) between five board-certified breast radiologists and the DL system (mean ΔAUROC, +0.04 in favor of the DL system). Radiologists’ performance improved when their predictions were averaged with DL’s predictions [mean ΔAUPRC (area under the precision-recall curve), +0.07]. We demonstrated the generalizability of the DL system using multiple datasets from Poland and the United States. An additional reader study on a Polish dataset showed that the DL system was as robust to distribution shift as radiologists. In subgroup analysis, we observed consistent results across different cancer subtypes and patient demographics. Using decision curve analysis, we showed that the DL system can reduce unnecessary biopsies in the range of clinically relevant risk thresholds. This would lead to avoiding biopsies yielding benign results in up to 20% of all patients with BI-RADS category 4 lesions. Last, we performed an error analysis, investigating situations where DL predictions were mostly incorrect. This exploratory work creates a foundation for deployment and prospective analysis of DL-based models for breast MRI.
Engineering Caldicellulosiruptor bescii with Surface Layer Homology Domain-Linked Glycoside Hydrolases Improves Plant Biomass Solubilization
Authors: Laemthong Tunyaboon , Bing Ryan G. , Crosby James R. , Adams Michael W. W. , Kelly Robert M.
Published: September 2022

Caldicellulosiruptor
species hold promise as microorganisms that can solubilize the carbohydrate portion of lignocellulose and subsequently convert fermentable sugars into bio-based chemicals and fuels. Members of the genus have surface layer (S-layer) homology domain-associated glycoside hydrolases (SLH-GHs) that mediate attachment to biomass as well as hydrolysis of carbohydrates.
Caldicellulosiruptor bescii
, the most studied member of the genus, has only one SLH-GH.
A Novel FadL Homolog, AltL, Mediates Transport of Long-Chain Alkanes and Fatty Acids in Acinetobacter venetianus RAG-1
Authors: Liu Jia , Chen Shuai , Zhao Bo , Li Guoqiang , Ma Ting
Published: September 2022

Petroleum pollution has caused great harm to the natural environment, and alkanes are the main components of petroleum. Many Gram-negative bacteria can use alkanes as carbon and energy sources, which is an important strategy for oil pollution remediation.
Genetic Divergence of Vibrio vulnificus Clinical Isolates with Mild to Severe Outcomes
Authors: Kling Kendall , Trinh Sonya A. , Leyn Semen A. , Rodionov Dmitry A. , Rodionov Ivan D. , Herrera Alfa , Cervantes Kasey , Pankey George , Ashcraft Deborah , Ozer Egon A. , Godzik Adam , Satchell Karla J. F.
Published: September 2022

Vibrio vulnificus
is an aquatic pathogen that is capable of causing severe disease in humans. Previous studies have suggested that pathogenic isolates were restricted to certain phylogenetic lineages and possibly toxinotype.