bluuebunny/crossref_metadata_2025 huggingface dataset:
Stage 4N neuroblastoma before and during the era of anti‐GD2 immunotherapy
Authors: Kushner Brian H. , LaQuaglia Michael P. , Cardenas Fiorella Iglesias , Basu Ellen M. , Gerstle Justin T. , Kramer Kim , Roberts Stephen S. , Wolden Suzanne L. , Cheung Nai‐Kong V. , Modak Shakeel
Published: August 2023

Patients with stage 4N neuroblastoma (distant metastases limited to lymph nodes) stand out as virtually the only survivors of high‐risk neuroblastoma (HR‐NB) before myeloablative therapy (MAT) and immunotherapy with anti‐GD2 monoclonal antibodies (mAbs) became standard. Because no report presents more recent results with 4N, we analyzed our large 4N experience. All 51 pediatric 4N patients (<18 years old) diagnosed 1985 to 2021 were reviewed. HR‐NB included MYCN‐nonamplified 4N diagnosed at age ≥18 months and MYCN‐amplified 4N. Among 34 MYCN‐nonamplified high‐risk patients, 20 are relapse‐free 1.5+ to 37.5+ (median 12.5+) years post‐diagnosis, including 13 without prior MAT and 5 treated with little (1 cycle; n = 2) or no mAb (n = 3), while 14 patients (7 post‐MAT, 8 post‐mAbs) relapsed (all soft tissue). Of 15 MYCN‐amplified 4N patients, 7 are relapse‐free 2.1+ to 26.4+ (median 11.6+) years from the start of chemotherapy (all received mAbs; 3 underwent MAT) and 4 are in second remission 4.2+ to 21.8+ years postrelapse (all soft tissue). Statistical analyses showed no significant association of survival with either MAT or mAbs for MYCN‐nonamplified HR‐NB; small numbers prevented these analyses for MYCN‐amplified patients. The two patients with intermediate‐risk 4N (14‐months‐old) are relapse‐free 7+ years postresection of primary tumors; distant disease spontaneously regressed. The natural history of 4N is marked by NB confined to soft tissue without early relapse in bones or bone marrow, where mAbs have proven efficacy. These findings plus curability without MAT, as seen elsewhere and at our center, support consideration of treatment reduction for MYCN‐nonamplified 4N.
Bank income smoothing behaviours under expansionary and recessionary economic environments: New evidence using micro‐data sample
Authors: Aggelopoulos Eleftherios , Papageorgiou Theofanis , Iakovidou Melpo , Giannopoulos Vasilios
Published: August 2023

The income smoothing (IS) literature connected with changes in the external environment provides unclear results whether this phenomenon occurs in expansion or in crisis. Given that a substantial amount of credit risk is generated in retail banking, this study exploits a large number of micro‐loan portfolio level data of a systemic Greek bank and examines, for the first time, the IS behaviour at the retail banking level, contrasting the expansion period (2006–2008) with the financial crisis period (2009–2011). This specific case study provides more granular data compared with traditional archival studies, thus allowing the immediate and more frequent identification of exogenous (such as crisis effects) and endogenous (such as the geographic origination of loan portfolios) features that may affect IS practices. Based on the association between pre‐provision loan income and loans loss provisions as a proxy for IS, we employ the robust Mean Group estimator (Pesaran and Smith, Journal of Econometrics, 1995;68(1):79–113) and find that this association is higher in expansionary periods and declines in recession. Moreover, we conclude that the IS behaviour is affected by geographical features of loan portfolios.
Market forces in healthcare insurance: The impact of healthcare reform on regulated competition revisited
Authors: Bikker Jacob A. , Bekooij Jack G. J.
Published: August 2023

The Dutch healthcare insurance reform in 2006 replaced the dual system of public and private insurance with a single compulsory health insurance scheme, in which insurance providers compete for customers in a free market. This paper investigates whether competition among healthcare insurers has indeed increased and their efficiency has improved. We measure competition directly from either shifts in market shares, or developments in profits, using Dutch regulatory data. We find that a structural break occurs after the reform: competition is significantly higher after 2006 than before. This holds both for the analysis based on shifts in market shares and that based on profits. Several robustness tests confirm this outcome. Hence, the reform has had a significant impact. Nevertheless, we find that the health insurance sector is still less competitive than financial sectors such as banking and life insurance.
Sustainability and modernization of agricultural irrigation: A comparative assessment of two irrigation schemes
Authors: Çetin Öner , Fayrap Aynur , Yolcu Ramazan
Published: August 2023

In this study, two different irrigation schemes in Turkey were evaluated. One is Devegeçidi irrigation, which was put into operation in 1972. The command area is 5800 ha, and farmers used surface irrigation. Ergani irrigation, a modern irrigation scheme using drip and/or sprinkler irrigation systems with an irrigation area of 1866 ha, was put into operation in 2021. The average total water use (TWU), irrigation efficiency (IE), water economic productivity (WEP) and net income (NI) were 11,728 m3 ha−1, 45%, $0.21 m−3and $2354 ha−1in the Devegecidi irrigation, respectively, and all the same criteria results were 6189 m3 ha−1, 81%, $0.78 m−3and $4789 ha−1in the Ergani irrigation, respectively. In addition, irrigation water productivities (IWPs) in wheat, cotton and corn for the Devegeçidi irrigation were 0.78, 0.47 and 1.21 kg m−3, while those values were 0.89, 0.89 and 2.26 kg m−3in the Ergani irrigation scheme, respectively. The study results show that the modernization of irrigation systems is significantly important in saving irrigation water and increasing the income of farmers and water productivity. These indicators can guide decision makers in the modernization of irrigation systems.
LncRTPred: Predicting RNA–RNA mode of interaction mediated by lncRNA
Authors: Das Gourab , Das Troyee , Parida Sibun , Ghosh Zhumur
Published: August 2023

Long non‐coding RNAs (lncRNAs) play a significant role in various biological processes. Hence, it is utmost important to elucidate their functions in order to understand the molecular mechanism of a complex biological system. This versatile RNA molecule has diverse modes of interaction, one of which constitutes lncRNA–mRNA interaction. Hence, identifying its target mRNA is essential to understand the function of an lncRNA explicitly. Existing lncRNA target prediction tools mainly adopt thermodynamics approach. Large execution time and inability to perform real‐time prediction limit their usage. Further, lack of negative training dataset has been a hindrance in the path of developing machine learning (ML) based lncRNA target prediction tools. In this work, we have developed a ML‐based lncRNA–mRNA target prediction model‐ ‘LncRTPred’. Here we have addressed the existing problems by generating reliable negative dataset and creating robust ML models. We have identified the non‐interacting lncRNA and mRNAs from the unlabelled dataset using BLAT. It is further filtered to get a reliable set of outliers. LncRTPred provides a cumulative_model_score as the final output against each query. In terms of prediction accuracy, LncRTPred outperforms other popular target prediction protocols like LncTar. Further, we have tested its performance against experimentally validated disease‐specific lncRNA–mRNA interactions. Overall, performance of LncRTPred is heavily dependent on the size of the training dataset, which is highly reflected by the difference in its performance for human and mouse species. Its performance for human species shows better as compared to that for mouse when applied on an unknown data due to smaller size of the training dataset in case of mouse compared to that of human. Availability of increased number of lncRNA–mRNA interaction data for mouse will improve the performance of LncRTPred in future. Both webserver and standalone versions of LncRTPred are available. Web server link: http://bicresources.jcbose.ac.in/zhumur/lncrtpred/index.html. Github Link: https://github.com/zglabDIB/LncRTPred.
Nrf2 as a therapeutic target in acetaminophen hepatotoxicity: A case study with sulforaphane
Authors: Etemadi Yasaman , Akakpo Jephte Y. , Ramachandran Anup , Jaeschke Hartmut
Published: August 2023

Acetaminophen (APAP) overdose can cause severe liver injury and acute liver failure. The only clinically approved antidote, N‐acetylcysteine (NAC), is highly effective but has a narrow therapeutic window. In the last 2 decades, activation of the transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2), which regulates acute phase proteins and antioxidant defense genes, has emerged as a putative new therapeutic target against APAP hepatotoxicity. However, virtually all studies that propose Nrf2 activation as mechanism of protection used prolonged pretreatment, which is not a clinically feasible approach to treat a drug overdose. Therefore, the objective of this study was to assess if therapeutic activation of Nrf2 is a viable approach to treat liver injury after APAP overdose. We used the water‐soluble Nrf2 activator sulforaphane (SFN; 5 mg/kg) in a murine model of APAP hepatotoxicity (300 mg/kg). Our results indicate that short‐term treatment (≤3 h) with SFN alone did not activate Nrf2 or its target genes. However, posttreatment with SFN after APAP partially protected at 6 h likely due to more rapid activation of the Nrf2‐target gene heme oxygenase‐1. A direct comparison of SFN with NAC given at 1 h after APAP showed a superior protection with NAC, which was maintained at 24 h unlike with SFN. Thus, Nrf2 activators have inherent problems like the need to create a cellular stress to activate Nrf2 and delayed adaptive responses which may hamper sustained protection against APAP hepatotoxicity. Thus, compared to the more direct acting antidote NAC, Nrf2 activators are less suitable for this indication.
Ultrasound features and differential diagnosis for superficial nodular fasciitis
Authors: Zhuang Nan , Lyu Heng , Zhao Chenyang , Zhang Yusen , Dong Licong , Luo Haiyu , Tian Yun , Xie Lu , Wu Wangjie , Liu Li , Sun Desheng , Xie HaiQin
Published: August 2023

Background

Nodular fasciitis (NF) has nonspecific clinical manifestations and is often misdiagnosed as sarcoma. The investigations of imaging methods for NF were limited.

Objective

To analyze the ultrasound (US) features of NF, and to evaluate the diagnostic value of US for NF.

Materials and Methods

A total of 61 NF patients were recruited retrospectively, and 551 lesions in the subcutaneous fat layer were included for comparison. We evaluated the ultrasound features of the patients and divided the NF cases into three types. Chi‐square test or Fisher exact test were conducted to detect the potential difference in the distributions of three types in the two groups.

Results

Among the 61 NF cases, 65.6% were in the upper extremities (n = 40). The proportion of type 1, 2, and 3 were 57.4%, 24.6%, and 18.0%, respectively. NF were significantly more likely locating in the upper extremities than the other soft tissue tumors (p < 0.001). Type 1 and type 2 of sonographic features were significantly more commonly observed in NF than other soft tissue tumors among the three types (p < 0.001).

Conclusion

The type 1 and type 2 of US features can help to distinguish NF from other lesions. US has great potential to improve the diagnostic accuracy and reduce the unnecessary surgery.
Laterality in roe deer embryos implantation
Authors: Chirichella Roberta , Apollonio Marco , Luccarini Siriano , Berlinguer Fiammetta
Published: August 2023

Female reproductive success is one of the most important life‐history traits to be monitored when determining population dynamics in free‐ranging ungulates. Several studies have described how phenotypic characteristics of the mother, climatic conditions, population status, and habitat can impact on potential reproductive output in wild ungulates. However, little is known regarding the internal, physiological factors, that may account for differences in implantation rates. The present study investigated the differences in implantation rates and site on the basis of site and number of ovulations through the examination of about 3000 intact uteri collected from pregnant roe deer does (Capreolus capreolus). Although ovulation occurs with the same frequency in the left and right ovary, we revealed a higher frequency of embryos implantation in the left uterine horn in odd litter size, demonstrating that embryos can migrate between the uterine horns. In our study, a greater proportion of reproductive wastage was associated to females with three and four corpora lutea and interestingly, in relation to the site of ovulation, the percentage of corpora lutea that did not correspond to a fetus was higher in the right ovary than in the left one (73.2% vs. 26.8%). Our research described for the first time the absence of laterality in ovulation and the presence of laterality in implantation in roe deer, thus laying the foundations for in‐depth studies about the functionality of this uterine side and for comparisons with populations located in other geographical areas to understand whether it is a widespread phenomenon or a local adaptation.
A comprehensive study of oxidative stress‐related effects on the prognosis and drug therapy of cervical cancer
Authors: Sheng Nan , He Chenyun , Jin Xiaoxia , Meng Qi , Gu Panyun , Ding Shu , Liu Hong , Xu Yunzhao
Published: August 2023

Background

Cervical cancer (CC) is a serious global disease with poor prognoses and a significant recurrence rate in patients with advanced disease. Oxidative stress (OS) greatly influences many types of human cancers, making it crucial to understand the functional mechanisms of OS‐related genes in CC.

Methods

The transcriptome and clinical data of three normal samples and 306 patients with CC were obtained from The Cancer Genome Atlas dataset. The GSE44001 dataset was acquired from the Gene Expression Omnibus database. OS‐related subtypes in the cohort with CC were identified using unsupervised hierarchical clustering, univariate Cox analysis, gene set enrichment analysis (GSEA), and least absolute shrinkage and selection operator regression analysis. Additionally, molecular pathways that differ across subtypes were determined and OS‐related genes linked to the prognosis of patients of CC were determined. Finally, a clinical prognostic gene signature was developed and validated. The relative infiltration level of immune cell subpopulations in different risk groups and subtypes was evaluated using the cell‐type identification by estimating relative subsets of RNA transcripts (CIBERPORT) algorithm and single‐sample GSEA (ssGSEA) techniques.

Results

The present study established two distinct OS subtypes (OS clusters A and B). Analysis using ssGSEA and CIBERSPORT revealed that OS cluster B exhibited a significant level of immune infiltration. A clinical prognostic gene signature was established using OS‐related characteristic genes identified by examining the differentially expressed genes across both subtypes. Furthermore, patients with CC were grouped into high‐ and low‐risk groups, with the low‐risk group showing higher survival rates. Additionally, these individuals exhibited significant advantages in terms of survival and immunotherapy. Receiver operating characteristic curve analysis demonstrated the higher predictive value of the clinical prognostic gene signature. The outcomes of the validation group depicted congruence with those recorded in the training group.

Conclusions

A new model was constructed based on eight OS‐related characteristic genes to aid the prediction of the survival rates of individuals with CC. The present study contributes to the existing literature on the mechanisms of OS genes in CC and offers a fresh perspective for future advancements in immunotherapy for such individuals.
Inequitable representation of Black boys in gifted and talented education, Advanced Placement, and special education
Authors: Ford Donna Y. , Hines Erik M. , Middleton Tanya J. , Moore James L.
Published: August 2023

Black boys are overrepresented in special education (SPED) and underrepresented in gifted and talented education, Advanced Placement, and other opportunities for advanced learners. Conversely, they are overrepresented in SPED. In this article, we address the vicious cycle of deficit thinking and intelligence test inequities—the consequences and impact on Black males. The impact of high‐stakes testing and racial prejudice and discrimination is stark. We present an equity formula to guide readers in all roles in setting quantifiable equity goals. Recommendations are provided.
Gray Matter Changes Following Mild COVID‐19: An MR Morphometric Study in Healthy Young People
Authors: Perlaki Gábor , Darnai Gergely , Arató Ákos , Alhour Husamalddin Ali , Szente Anna , Áfra Eszter , Nagy Szilvia Anett , Horváth Réka , Kovács Norbert , Dóczi Tamás , Orsi Gergely , Janszky József
Published: August 2023

Background

Although COVID‐19 is primarily an acute respiratory infection, 5%–40% of patients develop late and prolonged symptoms with frequent neurological complaints, known as long COVID syndrome. The presentation of the disease suggests that COVID infection may cause functional and/or morphological central nervous system alterations, but studies published in the literature report contradictory findings.

Purpose

To investigate the chronic effects of COVID‐19 on cerebral grey matter in a group of young patients without comorbidities, with mild course of COVID infection and no medical complaints at the time of examination.

Study Type

Prospective.

Population

Thirty‐eight young (age = 26.6 ± 5.0 years; male/female = 14/24), adult participants who recovered from mild COVID infection without a history of clinical long COVID and 37 healthy control subjects (age = 25.9 ± 2.8 years; male/female = 14/23).

Field Strength/Sequence

Three Tesla, 3D T1‐weighted magnetization‐prepared rapid gradient‐echo, 2D T2‐weighted turbo spin‐echo.

Assessment

MRI‐based morphometry and volumetry along with neuropsychological testing and self‐assessed questionnaire.

Statistical Tests

Fisher's exact test, Mann–Whitney U‐test, and multiple linear regression analyses were used to assess differences between COVID and healthy control groups. P < 0.05 was used as cutoff for significance.

Results

In the COVID group, significantly lower bilateral mean cortical thickness (left/right‐hemisphere: 2.51 ± 0.06 mm vs. 2.56 ± 0.07 mm, η2p = 0.102/2.50 ± 0.06 mm vs. 2.54 ± 0.07 mm, η2p = 0.101), lower subcortical gray matter (57881 ± 3998 mm3 vs. 60470 ± 5211 mm3, η2p = 0.100) and lower right olfactory bulb volume (52.28 ± 13.55 mm3 vs. 60.98 ± 15.8 mm3, η2p = 0.078) were found. In patients with moderate to severe anosmia, cortical thickness was significantly lower bilaterally, as compared to patients without olfactory function loss (left/right‐hemisphere: 2.50 ± 0.06 mm vs. 2.56 ± 0.05 mm, η2 = 0.173/2.49 ± 0.06 mm vs. 2.55 ± 0.05 mm, η2 = 0.189). Using further exploratory analysis, significantly reduced cortical thickness was detected locally in the right lateral orbitofrontal cortex in the COVID group (2.53 ± 0.10 mm vs. 2.60 ± 0.09 mm, η2p = 0.112).

Data Conclusion

Even without any subjective or objective neurological complaints at the time of the MR scan, subjects in the COVID group showed gray matter alterations in cortical thickness and subcortical gray matter volume.

Level of Evidence

2

Technical Efficacy

Stage 3
Soil health restoration in degraded lands: A microbiological perspective
Authors: Kumar Adarsh , Das Abinash , Singh Dikchha , Das Malay Kumar , Srivastava Gyan Prakash , Singh Jyoti Prakash , Tilgam Jyotsana , Thapa Shobit , Das Sudipta , Chakdar Hillol
Published: August 2023

Land degradation is one of the most pressing environmental problems of the 21st century particularly due to its impact on global food security and environmental quality through the loss of biodiversity and ecosystem services. Land degradation happens at an accelerated rate and affects regions inhabited by more than one‐third population of the world. This phenomenon resulted in a dramatic reduction in the productivity of cropland and rangeland of world thus threatening the environmental quality and food security. It manifests in various forms such as desertification, soil erosion, sodicity, salinity, heavy metal contamination, pesticide contamination, declining soil fertility, and fate of polycyclic aromatic hydrocarbons. The world now has a real chance for the next generation to grow sustainably and eliminate acute food scarcity. Microbes, as vital elements of soil, play an important role in maintaining soil biological properties and fertility. Due to their multifarious biological functions and metabolic uniqueness, microorganisms can fix or solubilize nutrients, add organic matters to the soil to improve its quality. Many of the microorganisms can produce biological compounds or enzymes, which can degrade or scavenge toxic substances from the soils. In this review, we have discussed in detail how diverse microorganisms can help to restore different types of degraded lands. The limitations in application of microorganisms in restoration of soil health and possible scopes to improve the applicability have also been discussed here.
The response of glaciers and glacial lakes to climate change in the Southeastern Tibetan Plateau over the past three decades
Authors: Dou Xiangyang , Fan Xuanmei , Wang Xin , Fang Chengyong , Lovati Marco , Zou Chengbin
Published: August 2023

With global warming, changes in glaciers and glacial lakes on the Tibetan Plateau call for a serious inspection. The Southeastern Tibetan Plateau (SETP) is a typical monsoonal marine glacier area that is extremely vulnerable to climate change. It is affected by both humid and warm Indian Ocean currents. Outlines of glaciers and glacial lakes in SETP have been extracted from Landsat satellite images with an automatic extraction method based on image compositing with Google Earth Engine and Random Forest algorithm. Alongside the outlines, meteorological data have been collected from 1990 to 2021. The results show that since 1990 the glacier area of SETP has retreated by about 2165.33 km2 (~25.28%), the glacial lake area has increased by about 36.41 km2 (~21.45%), and their number has increased by 477 (~27.32%). The reliability and scientific validity of this study is proven by comparison with existing glacier inventories. By analyzing the meteorological data, the inverse correlation between the glacier area and temperature has been found. Despite decreases in cumulative precipitation, the glacial lake level rise and consequent area expansion have been observed. A fitting equation for the response pattern of glacier changes to temperature and precipitation change is presented and will provide a basis for future studies.
Survival after induction chemotherapy in locoregional advanced nasopharyngeal carcinoma: An updated systematic review and meta‐analysis
Authors: Meng Yiyu , Huang Chao , Huang Wu
Published: August 2023

Background

Induction chemotherapy (ICT) augmentation is a common strategy for standard concurrent chemoradiotherapy (CCRT) of locoregionally advanced nasopharyngeal carcinoma (NPC). The survival condition is a crucial issue for patients with locoregionally advanced NPC. The survival of ICT patients with CCRT treatment versus standard CCRT alone should be elucidated via a systemic review and meta‐analysis of randomized clinical trials.

Methods

We compared ICT with CCRT and CCRT alone treatment to determine if ICT with CCRT can be associated with a significant benefit of survival conditions versus CCRT. Different survival indicators were analyzed for the ICT with CCRT. Twelve studies with a total of 3711 patients with locoregionally advanced NPC were enrolled. The focused outcome was the overall survival, progression‐free survival, distant metastasis‐free survival, and locoregional recurrence‐free survival.

Results

Our results showed that ICT with CCRT is associated with a significant benefit for the overall survival status versus CCRT treatment. Similar significant benefits in the survival condition were seen in progression‐free survival, distant metastasis‐free survival, and locoregional recurrence‐free survival.

Conclusions

The updated meta‐analysis results suggest that the ICT with CCRT might be associated with significant benefits of survival in overall, progression‐free, distant metastasis‐free, as well as locoregional recurrence‐free dimensions versus CCRT treatment. However, the bias of different kinds, doses, and regimens of chemotherapy agents and radiotherapy should not be ignored.
Association between depression and tinnitus in US adults: A nationally representative sample
Authors: Lin Xing , Liu Yang , Chen Zhen , Wei Yihan , Lin Jianwei , Chen Chenyu , Lin Wei , Xu Yuanteng
Published: August 2023

Background

Data from the National Health and Nutrition Examination Survey (NHANES) has not been previously utilized to study the prevalence of tinnitus and depression among adults over 20 years old, nor the impact of tinnitus on depression.

Objective

The aim of this study was to evaluate the relationship between tinnitus and depression among adults in the United States.

Materials and Methods

This cross‐sectional study drew upon data from the 2005–2018 NHANES, incorporating adults aged 20 and older who had completed the tinnitus and depression questionnaire. Depression was assessed using the PHQ‐9 questionnaire. Multivariate logistic regression models, subgroup analyses, and sensitivity analyses were performed to examine the association between tinnitus and depression.

Results

This nationally representative study included 10,409 participants, of whom 17.69% reported experiencing tinnitus. The prevalence of depression was 6.2% among those without tinnitus and 15.1% among those with tinnitus (p < .0001). Accounting for potential confounders such as demographic and socioeconomic variables, participants who experienced tinnitus were more likely to exhibit depression symptoms (adjusted odds ratio = 2.0, 95% confidence interval = 1.61–2.48). Subgroup analyses further suggested that tinnitus was associated with an increased prevalence of depression across all subgroups. Sensitivity analysis affirmed these findings.

Conclusions

This study suggests that there is a significant association between tinnitus and the risk of depression in the adult population of the United States, emphasizing the importance of psychological factors in the clinical management of tinnitus.

Level of Evidence

2b.
Methanogens limited to lower rhizosphere and to an atypical salt marsh niche along a pristine intertidal mangrove continuum
Authors: Euler Sebastian , Jeffrey Luke C. , Maher Damien T. , Johnston Scott G. , Sugimoto Ryo , Tait Douglas R.
Published: August 2023

Mangroves are valuable ecosystems that facilitate primary production, carbon sequestration, and regulation of greenhouse gas (GHG) cycles in coastal sediments, with microorganisms playing key roles. Specialized bacteria and archaea compete for energy and resources in mangrove sediments to inhabit optimal ecological niches and can produce or consume methane (CH4)—a potent GHG—in the process. CH4 cycling in mangroves has gained growing attention, yet uncertainties regarding functional and spatial distributions of microorganisms remain. Here, we demonstrate that in a pristine mangrove forest, CH4 concentrations and methanogen communities are concentrated within lower or below rhizosphere depths. We also reveal atypical niches for methanogens in the upper tidal salt marsh zone where vegetation is sparse and highest methanogens abundances were detected at deepest depths (4715 reads g−1) despite relatively high redox potentials (> 250 mV). Pore water CH4 concentrations were highest at the deepest depth within the mangrove forest (max. 3.40 ± 0.21 μM) and coincided with the highest sediment CH4 fluxes (276.4 ± 54.2 μmol m−2d−1) and methanotroph abundances at the surface (1309 reads g−1). Sediment CH4 oxidation fractions between the deepest (60 cm) and shallowest (5 cm) depths were estimated between 18.8% and 64.9%. Positive correlation between crab burrows and CH4 fluxes suggests that CH4 from deeper sediment and salt marsh niches can be transported via conduits to the atmosphere. The spatial data from this study highlights the importance of investigating CH4 dynamics across estuarine ecosystem gradients to better understand the complex roles of vital coastal vegetation zones in the face of a changing climate.
Transforming the untransformable with knockout minicircles: High‐efficiency transformation and vector‐free allelic exchange knockout in the fish pathogen Photobacterium damselae
Authors: Rudenko Oleksandra , Baseggio Laura , McGuigan Fynn , Barnes Andrew C.
Published: August 2023

Gene inactivation studies are critical in pathogenic bacteria, where insights into species biology can guide the development of vaccines and treatments. Allelic exchange via homologous recombination is a generic method of targeted gene editing in bacteria. However, generally applicable protocols are lacking, and suboptimal approaches are often used for nonstandard but epidemiologically important species. Photobacterium damselae subsp. piscicida (Pdp) is a primary pathogen of fish in aquaculture and has been considered hard to transform since the mid‐1990s. Consequently, conjugative transfer of RK2/RP4 suicide vectors from Escherichia coli S17‐1/SM10 donor strains, a system prone to off‐target mutagenesis, was used to deliver the allelic exchange DNA in previous studies. Here we have achieved efficient electrotransformation in Pdp using a salt‐free highly concentrated sucrose solution, which performs as a hypertonic wash buffer, cryoprotectant, and electroporation buffer. High‐efficiency transformation has enabled vector‐free mutagenesis for which we have employed circular minimalistic constructs (knockout minicircles) containing only allelic exchange essentials that were generated by Gibson assembly. Preparation of competent cells using sucrose and electroporation/integration of minicircles had virtually no detectable off‐target promutagenic effect. In contrast, a downstream sacB selection apparently induced several large deletions via mobilization of transposable elements. Electroporation of minicircles into sucrose‐treated cells is a versatile broadly applicable approach that may facilitate allelic exchange in a wide range of microbial species. The method permitted inactivation of a primary virulence factor unique to Pdp, apoptogenic toxin AIP56, demonstrating the efficacy of minicircles for difficult KO targets located on the high copy number of small plasmids.
Protumorigenic role of the atypical cadherin FAT1 by the suppression of PDCD10 via RelA/miR221‐3p/222‐3p axis in glioblastoma
Authors: Malik Nargis , Kundu Archismita , Gupta Yakhlesh , Irshad Khushboo , Arora Manvi , Goswami Sanjeev , Mahajan Swati , Sarkar Chitra , Suri Vaishali , Suri Ashish , Chattopadhyay Parthaprasad , Sinha Subrata , Chosdol Kunzang
Published: August 2023

The atypical cadherin FAT1 function either as a pro or antitumorigenic in tumors of different tissue origins. Our group previously demonstrated the protumorigenic nature of FAT1 signaling in glioblastoma (GBM). In this study, we investigated how FAT1 influences the expression of clustered oncomiRs (miR‐221‐3p/miR‐222‐3p) and their downstream effects in GBM. Through several experiments involving the measurement of specific gene/microRNA expression, gene knockdowns, protein and cellular assays, we have demonstrated a novel oncogenic signaling pathway mediated by FAT1 in glioma. These results have been verified using antimiRs and miR‐mimic assays. Initially, in glioma‐derived cell lines (U87MG and LN229), we observed FAT1 as a novel up‐regulator of the transcription factor NFκB‐RelA. RelA then promotes the expression of the clustered‐oncomiRs, miR‐221‐3p/miR‐222‐3p, which in turn suppresses the expression of the tumor suppressor gene (TSG), PDCD10 (Programmed cell death protein10). The suppression of PDCD10, and other known TSG targets (PTEN/PUMA), by miR‐221‐3p/miR‐222‐3p, leads to increased clonogenicity, migration, and invasion of glioma cells. Consistent with our in‐vitro findings, we observed a positive expression correlation of FAT1 and miR‐221‐3p, and an inverse correlation of FAT1 and the miR‐targets (PDCD10/PTEN/PUMA), in GBM tissue‐samples. These findings were also supported by publicly available GBM databases (The Cancer Genome Atlas [TCGA] and The Repository of Molecular Brain Neoplasia Data [Rembrandt]). Patients with tumors displaying high levels of FAT1 and miR‐221‐3p expression (50% and 65% respectively) experienced shorter overall survival. Similar results were observed in the TCGA‐GBM database. Thus, our findings show a novel FAT1/RelA/miR‐221/miR‐222 oncogenic‐effector pathway that downregulates the TSG, PDCD10, in GBM, which could be targeted therapeutically in a specific manner.
Identifying Ferroptosis‐Related Genes Associated with Weight Loss Outcomes and Regulation of Adipocyte Microenvironment
Authors: Li Wanyang , Xu Hanyuan , Li Yao , Shi Xiaodong , Ma Zhaotian , Yang Fan , Chen Wei
Published: August 2023

Scope

The study is about the influence of ferroptosis‐related genes combined with the immune microenvironment exerted on weight control outcomes and systematic analysis.

Methods and results

Subcutaneous adipose tissue (sWAT) samples from 11 subjects with good outcome and 10 subjects with poor outcome in weight management are obtained from the Gene Expression Omnibus database. The results are validated in vivo in animal models with different weight loss outcomes. The CIBERSORT algorithm is used to evaluate the differences in immune cell infiltration in each sample. Patients with poor outcome have higher levels of ferroptosis in the adipose tissue. Remarkable differences in cytokine production, nuclear factor kappa‐B(NF‐κB) transcription factor activity, leukocyte migration involved in the inflammatory response, and other biological processes are also observed compared to that in the well‐controlled group. Aldo‐keto reductase family 1‐member C1(AKR1C1), nuclear receptor coactivator 4(NCOA4), and glutamate‐cysteine ligase catalytic subunit(GCLC) are identified as core predictive markers and their expression patterns are confirmed in animal models.

Conclusions

Ferroptosis and its mediated inflammation play an important role in long‐term weight control, and analyses of the role of ferroptosis‐related genes(FRGs) in weight control may provide new potential therapeutic targets for long‐term weight control. Anti‐inflammatory diets that mitigate inflammatory responses and affect ferroptosis may be considered in the future to improve weight control.
A novel large‐signal GaN HEMT modeling based on harmonic mean
Authors: Fang Heng , Chen Yang , Liang Yan , Zhang Yong , Xu Yuehang , Xu Ruimin , Yan Bo
Published: August 2023

A novel large signal compact modeling for GaN HEMT has been proposed in this paper, and the harmonic mean is used to simulate the I‐V curves, combining the saturation and the linear region. The traditional compact modelings has two typical forms, the empirical modeling and the physical modeling. The empirical modeling is accurate and fast, but lacking the physical meaning. On the contrary, the physical modeling derived from the physical equation, is more complex, with the low speed and the poor convergence. This novel modeling inherently has both advantages, the fast speed, and so forth, and the physical meaning. The saturation region covers the most states of the power amplifiers, and Chih‐Tang Sah equation with clear physical meanings is adopted in this region. In linear region, on the contrary, the current varies more steeply with the voltage, and thus the empirical formula is used.
Malnutrition risk, outcomes, and costs among older adults undergoing elective surgical procedures: A retrospective cohort study
Authors: Le Bill , Flier Suzanne , Madill Janet , Joyes Catherine , Dawson Emily , Wellington Chris , Adekunte Shadia , Cheng Davy , John‐Baptiste Ava
Published: August 2023

Background

We examine here the association between malnutrition risk and adverse health outcomes among older adult patients undergoing elective surgical procedures.

Methods

We conducted a retrospective study using linked clinical and administrative databases. Malnutrition risk was assessed prior to surgery, defined by unintentional weight loss and decreased food intake. We performed a logistic regression analysis of the primary outcome, a composite adverse outcome measure, including death, bleeding, pneumonia, and other surgical complications. We conducted Fine‐Gray proportional hazard regression analysis of hospital length of stay (LOS). We performed a generalized linear regression analysis of in‐hospital cost data. All regression analyses controlled for frailty, age, sex, surgical category, and comorbidities.

Results

Of a total of 3457 older adult elective surgical patients (65–102 years), 310 (9.0%) screened positive for malnutrition risk. In multivariable regression analyses, malnutrition risk was associated with an increased risk of the composite adverse outcome (odds ratio [OR] = 1.74; 95% CI = 1.25–2.39), higher hospitalization costs (relative cost = 1.84; 95% CI = 1.59–2.13), and a decreased risk of discharge from the hospital (hazard ratio = 0.67; 95% CI = 0.59–0.77) compared with those who screened negative.

Conclusion

Older adult patients with malnutrition risk were at an increased risk of adverse surgical outcomes, had longer LOS in the hospital, and incurred higher costs of care. It is important to screen for malnutrition risk and refer older adults for dietetic consults prior to elective surgery.
Challenges and career consequences of internationally educated nurses: Empirical research qualitative
Authors: Miyata Chiharu
Published: August 2023

Aim

To explore challenges, and career consequences of internationally educated nurses, and considerations of development policy, education, and support for them from the perspective of nursing administrators.

Design

This study applied a qualitative description design.

Methods

A semi‐structured interview guideline were used, interviewed eight internationally educated nurses and nine nursing administrators were chosen based on a purposive sampling method. Each interview was recorded and transcribed, after which it was analyzed using the qualitative content analysis method.

Results

Three categories were extracted as the challenges and career consequences, and the support they expect to organization of internationally educated nurses: “Language barrier,” “Transition to recover their confidence and increase motivation,” and “Close support from many quarters”. Four categories were extracted as key considerations of support to internationally educated nurses that nursing administrators had recognized: “Clarification of career path”, “Support for insufficient language skills”, “Support for their career reconstruction”, “Comprehensive support”. This research found that nursing administrators had recognized necessity of adequate work‐related support, it almost met the needs of internationally educated nurses. we need to make a clear policy how to develop internationally educated nurses as valuable human resource based on the evidence of further research relate to support practiced at each facility.

Patient or Public Contribution

There was no patient and public involvement since I only conducted interview to nurses in this study.
Structuring group work to provide a more positive student learning experience
Authors: Boerngen Maria A. , Rickard Justin W.
Published: August 2023

Group projects enable students to build valuable critical thinking and communication skills that are increasingly required for success in the agricultural industry. Group projects provide well‐documented benefits; however, associated challenges lead to student and instructor reluctance to engage in group work in the college classroom. Well‐structured group projects may allow greater focus on achieving learning objectives and less on conflict management. Therefore, this study examines how group project structure may affect students’ learning experiences and perception of group work. Students enrolled in a senior‐level agribusiness management course complete a semester‐long group project, working in instructor‐assigned groups, to design a business plan for an agri‐food industry start‐up company. It is structured to encourage teamwork and soft skill development, and to discourage social loafing. Questionnaires administered prior to, halfway through, and at the end of the project during seven face‐to‐face semesters preceding the COVID remote learning period identify students’ prior group project experiences, evaluate their groups’ progress, and measure their perception of the project's structural elements upon completion. Responses indicated 98% of students agreed that scaffolding the project into smaller components increased group success, 96% agreed that they clearly understood professor expectations, and 85% reported that this project provided more structure than they previously experienced in other group projects in college. A paired‐samples t‐test found a significantly positive increase in students’ mean opinion about group projects upon the completion of this project (p < 0.001). This study suggests structural elements that can provide students with a more positive learning experience through group work.
STARC OSTEOARCH: An open access resource for recording and sharing human osteoarchaeological data
Authors: Caruso Antonio , Karligkioti Anna , Selempa Gkampriella , Nikita Efthymia
Published: August 2023

This paper introduces an open access resource for recording and sharing macroscopic data on archaeological human skeletal remains: STARC OSTEOARCH. The resource was developed using a cloud collaboration service, Airtable, and it accommodates data collection on individual skeletons as well as disassociated commingled remains. The attributes covered include key information on demography (sex and age‐at‐death), taphonomy (zonation, anatomical preservation, weathering, fragmentation, and other types of post‐mortem alteration), diet (dental diseases and dental wear), mechanical stress (entheseal changes, osteoarthritis, Schmorl's nodes, and vertebral arthritis), biodistances (cranial metrics and nonmetrics and dental metrics and nonmetrics), and various pathological lesions. References and key descriptions of the categories per attribute have been incorporated in the resource to facilitate raw data sharing, which can be achieved using Airtable's sharing functionality. This initiative aims at promoting standard practices in the field and facilitating data collection and sharing.
Long‐term cancer outcomes after bariatric surgery
Authors: Adams Ted D. , Meeks Huong , Fraser Alison , Davidson Lance E. , Holmen John , Newman Michael , Ibele Anna R. , Playdon Mary , Hardikar Sheetal , Richards Nathan , Hunt Steven C. , Kim Jaewhan
Published: August 2023

Objective

Obesity is associated with increased cancer risk. Because of the substantial and sustained weight loss following bariatric surgery, postsurgical patients are ideal to study the association of weight loss and cancer.

Methods

Retrospectively (1982–2019), 21,837 bariatric surgery patients (surgery, 1982–2018) were matched 1:1 by age, sex, and BMI with a nonsurgical comparison group. Procedures included gastric bypass, gastric banding, sleeve gastrectomy, and duodenal switch. Primary outcomes included cancer incidence and mortality, stratified by obesity‐ and non‐obesity‐related cancers, sex, cancer stage, and procedure.

Results

Bariatric surgery patients had a 25% lower risk of developing any cancers compared with a nonsurgical comparison group (hazard ratio [HR] 0.75; 95% CI 0.69–0.81; p < 0.001). Cancer incidence was lower among female (HR 0.67; 95% CI 0.62–0.74; p < 0.001) but not male surgery patients, with the HR lower for females than for males (p < 0.001). Female surgery patients had a 41% lower risk for obesity‐related cancers (i.e., breast, ovarian, uterine, and colon) compared with nonsurgical females (HR 0.59; 95% CI 0.52–0.66; p < 0.001). Cancer mortality was significantly lower after surgery in females (HR 0.53; 95% CI 0.44–0.64; p < 0.001).

Conclusions

Bariatric surgery was associated with lower all‐cancer and obesity‐related cancer incidence among female patients. Cancer mortality was significantly lower among females in the surgical group versus the nonsurgical group.
How images of food become cravingly salient in obesity
Authors: Devoto Francantonio , Ferrulli Anna , Banfi Giuseppe , Luzi Livio , Zapparoli Laura , Paulesu Eraldo
Published: August 2023

Objective

This case‐control study was aimed at testing two main hypotheses: (i) obesity is characterized by neurofunctional alterations within the mesocorticolimbic reward system, a brain network originating from the midbrain ventral tegmental area (VTA); and (ii) these alterations are associated with a bias for food‐related stimuli and craving.

Methods

Normal‐weight individuals and individuals with obesity underwent a resting‐state functional magnetic resonance imaging scan and the assessment of impulsivity, food craving, appetite, and implicit bias for food and non‐food stimuli. The VTA was used as a seed to map, for each participant, the strength of its functional connections with the rest of the brain. The between‐group difference in functional connectivity was then computed, and brain‐behavior correlations were performed.

Results

Individuals with obesity showed hyper‐connectivity of the VTA with part of the ventral occipitotemporal cortex, recently found to be specialized for food images, and hypo‐connectivity with the left inferior frontal gyrus, devoted to cognitive control. VTA–ventral occipitotemporal cortex connectivity was positively associated with food craving and food‐related bias; the reverse correlation was observed for VTA–inferior frontal gyrus connectivity.

Conclusions

These findings reveal that, in obesity, food‐related visual stimuli become cravingly salient through an imbalanced connectivity of the reward system with sensory‐specific regions and the frontal cortex involved in cognitive control.
Diagnostic and Management Applications of ChatGPT in Structured Otolaryngology Clinical Scenarios
Authors: Qu Roy W. , Qureshi Uneeb , Petersen Garrett , Lee Steve C.
Published: August 2023

Objective

To evaluate the clinical applications and limitations of chat generative pretrained transformer (ChatGPT) in otolaryngology.

Study Design

Cross‐sectional survey.

Setting

Tertiary academic center.

Methods

ChatGPT 4.0 was queried for diagnoses and management plans for 20 physician‐written clinical vignettes in otolaryngology. Attending physicians were then asked to rate the difficulty of the clinical vignettes and agreement with the differential diagnoses and management plans of ChatGPT responses on a 5‐point Likert scale. Summary statistics were calculated. Univariate ordinal regression was then performed between vignette difficulty and quality of the diagnoses and management plans.

Results

Eleven attending physicians completed the survey (61% response rate). Overall, vignettes were rated as very easy to neutral difficulty (range of median score: 1.00‐4.00; overall median 2.00). There was a high agreement with the differential diagnosis provided by ChatGPT (range of median score: 3.00‐5.00; overall median: 5.00). There was also high agreement with treatment plans (range of median score: 3.00‐5.00; overall median: 5.00). There was no association between vignette difficulty and agreement with differential diagnosis or treatment. Lower diagnosis scores had greater odds of having lower treatment scores.

Conclusion

Generative artificial intelligence models like ChatGPT are being rapidly adopted in medicine. Performance with curated, easy‐to‐moderate difficulty otolaryngology scenarios indicate high agreement with physicians for diagnosis and management. However, a decreased quality in diagnosis is associated with decreased quality in management. Further research is necessary on ChatGPT's ability to handle unstructured clinical information.